PMID- 2303838 TI - Congenital Horner's syndrome with unilateral facial flushing. AB - Two patients with congenital Horner's syndrome had unilateral facial flushing. Both showed pupillary supersensitivity to epinephrine as well as anhidrosis on the affected side of the face and neck. Facial skin temperature after exercise increased on the intact side, but decreased on the affected side. Thermal vasodilation in the major portions of the face is regulated by sympathetic vasodilator fibres, and less predominantly by adrenergic vasoconstrictor fibres. The asymmetry of facial flushing may have been caused by impaired sympathetic vasodilation and further intensified by active vasoconstriction due to supersensitivity to circulating catecholamine on the affected side. PMID- 2303839 TI - Spasms. PMID- 2303840 TI - Pontine myelinolysis presenting with acute parkinsonism as a sequel of corrected hyponatraemia. PMID- 2303841 TI - Type 1 Arnold-Chiari malformation in a 77 year old woman. PMID- 2303842 TI - Effect of Pseudomonas cepacia colonization on survival and pulmonary function of cystic fibrosis patients. AB - We conducted a historical prospective study of 124 cystic fibrosis (CF) patients colonized with Pseudomonas cepacia (cases) and 124 sex and age matched non colonized CF patients (controls). Thirty-two of the colonized patients died in the first year following P. cepacia colonization compared to 8 of the control patients, a highly significant difference (p less than 0.001). In the second year, there was no significant difference in mortality between the two groups. Cases as a group had poorer pulmonary function and chest X-ray scores than controls up to 2 years before P. cepacia first appeared in their sputum or throat cultures. Regression analysis of pulmonary function tests (percent predicted FEV1 and RV/TLC) for each subject from 3 years before to 2 years after colonization revealed significant differences between cases and controls in slope for FEV1 and in slope and intercept for RV/TLC. When compared separately according to gender, the differences between cases and controls are significant in females but not in males. These results suggest that patients with poor pulmonary function are more prone to colonization with P. cepacia, that a subgroup of these patients will be dramatically affected and die within a year, and that the organism continues to exert a less dramatic negative effect on the pulmonary function of those patients who survive the initial acute effects of colonization, particularly in female patients. PMID- 2303843 TI - Age related changes in age of starting to smoke. AB - The Average Age of Starting to Smoke (AASS) has been reported to decline for younger birth cohorts. That apparent decline has been used to support a conclusion of an increase in smoking among younger individuals. However, in some cases the apparent decline is an artifact of the method of computation which arises when the quantity being averaged is related to a quantity used to classify subjects for comparison. In one other case, a second type of error arises because the distribution of smoking initiation with age changed in such a way that the proportion of individuals taking up smoking at older ages declined more rapidly than the proportion starting at younger ages. In fact, comparison of the 1970 National Health Interview Survey (NHIS) to the 1979/80 NHIS shows a uniform decrease in starting to smoke among teens and preteens. Examples are discussed which show that estimates of possible disease related factors actually experienced by a cohort are possible only if other suitable data are available for comparable representative sections of the population at different time periods and for different ages. PMID- 2303844 TI - The sick person effect. AB - Very often criteria by which subjects are selected for epidemiological studies are associated in some manner with their health. The Healthy Worker Effect (HWE) or Healthy Person Effect (HPE) is well known. Little has been said about the converse case in which selection is associated with decreased health status, the Sick Person Effect (SPE). The SPE may introduce a bias for some cohort, most clinical follow-up, and some case-control studies when risks are standardized against an inappropriate referent. We demonstrate the existence of the SPE in two studies. Study 1 compares the incidence of a number of different diseases among individuals who were selected as children for medical treatment with that among their siblings. Study 2 computes the Standardized Morbidity Ratios (SmRs) for various acute and chronic diseases for individuals who have reported particular chronic symptoms. The SPE is clearly apparent for all instances where the general population is taken as the referent. The HPE and SPE may present serious problems for the validity of conclusions with respect to risk levels. PMID- 2303845 TI - White blood cell count as a predictor of mortality: results over 18 years from the Normative Aging Study. AB - The ubiquitous white blood cell count (WBC) has rarely been analyzed as a predictor of future mortality. We examined WBC measured in prospective examinations of 2011 initially healthy men in the Normative Aging Study (mean age 47.5), followed for an average of 13.6 years with 27,402 man-years of observation. Between 1970 and 1987, 183 participants died. Mortality rates for men with baseline WBC over 9000 were 12.2/1000 man-years, 1.8-2.5 times those of men with lower WBC in each of three age groups. Proportional hazards models controlling for established risk factors including age, systolic blood pressure, cholesterol and smoking status, found WBC at the baseline exam to be an independent predictor of mortality over the following years. Even within the normal range, a difference of 1000 in the initial WBC increased the risk ratio by 1.2 (95% CI 1.1, 1.3). The relation of initial WBC to mortality was not affected by baseline age, body mass index (BMI), smoking or blood pressure. These findings are not explained by medication effects. We conclude that the WBC is an independent predictor of all-cause mortality. PMID- 2303846 TI - "Size" and "shape" variables in the presence of covariates: an application to the sudden infant death syndrome. AB - A "size measure independent of shape" is used to investigate differences in "size" and "shape" variables, defined as functions of weight and length at birth, between a random control group and victims of the Sudden Infant Death Syndrome (SIDS). At birth, the SIDS group has a lower mean size than the control group. After adjusting for maternal and environmental factors (covariates), there is a lessened but persistent difference in size, suggesting the existence of some undetected factor linked to sudden death in infants. PMID- 2303847 TI - Agreement of self-reported ovarian number following gynecologic surgery with medical record reports. AB - In case-control studies of breast cancer, cardiovascular disease, and osteoporosis, a woman's ovarian function may be considered as a main exposure, confounding factor, or effect modifier. To evaluate the agreement between self reported ovarian number following ovarian surgery for nonmalignant disease and medical record reports, we analyzed data from a population-based case-control study, the Cancer and Steroid Hormone Study. Reports on ovarian number after the most recent surgery for a who had been diagnosed with breast cancer and 496 control subjects. We then calculated agreement rates by comparing the number of ovaries indicated by the medical record with the number reported by the woman. Agreement rates on the presence or absence of ovaries exceeded 90% for both case and control subjects. Agreement rates on exact ovarian number exceeded 84% for both groups. Women who had been diagnosed with breast cancer had slightly higher agreement rates than did control women for both presence or absence of ovaries and exact ovarian number. Our data suggest that investigators can rely on self reported ovarian number as an accurate measure of actual ovarian number in women who have had surgery for nonmalignant conditions. PMID- 2303848 TI - A medical homily: old dogs do teach new tricks. PMID- 2303849 TI - Age-related diseases and normal aging: the nature of the relationship. PMID- 2303850 TI - The unit fragility index: an additional appraisal of "statistical significance" for a contrast of two proportions. PMID- 2303851 TI - Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis. AB - This paper is a study of the behavioral and spatial firing correlates of neurons in the rat postsubiculum. Recordings were made from postsubicular neurons as rats moved freely throughout a cylindrical chamber, where the major cue for orientation was a white card taped to the inside wall. An automatic video/computer system monitored cell discharge while simultaneously tracking the position of 2 colored light emitting diodes (LEDs) secured to the animal's head. The animal's location was calculated from the position of one of the LEDs and head direction in the horizontal plane calculated from the relative positions of the 2 LEDs. Approximately 26% of the cells were classified as head-direction cells because they discharged as a function of the animal's head direction in the horizontal plane, independent of the animal's behavior, location, or trunk position. For each head-direction cell, vectors drawn in the direction of maximal firing were parallel throughout the recording chamber and did not converge toward a single point. Plots of firing rate versus head direction showed that each firing-rate/head-direction function was adequately described by a triangular function. Each cell's maximum firing rate occurred at only one (the preferred) head direction; firing rates at head directions on either side of the preferred direction decreased linearly with angular deviation from the preferred direction. Results from 24 head-direction cells in 7 animals showed an equal distribution of preferred firing directions over a 360 degrees angle. The peak firing rate of head-direction cells varied from 5 to 115 spikes/sec (mean: 35). The range of head-direction angles over which discharge was elevated (directional firing range) was usually about 90 degrees, with little, if any, discharge at head directions outside this range. Quantitative analysis showed the location of the animal within the cylinder had minimal effect on directional cell firing. For each head-direction cell, the preferred direction, peak firing rate, and directional firing range remained stable for days. These results identify a new cell type that signals the animal's head direction in its environment. PMID- 2303852 TI - Head-direction cells recorded from the postsubiculum in freely moving rats. II. Effects of environmental manipulations. AB - The discharge characteristics of postsubicular head-direction cells in a fixed environment were described in the previous paper (Taube et al., 1990). This paper reports changes in the firing properties of head-direction cells following changes in the animal's environment. Head-direction cells were recorded from rats as they moved freely in a 76-cm-diameter gray cylinder. A white card, occupying 100 degrees of arc, was taped to the inside wall of the cylinder and served as the major orienting spatial cue in the animal's environment. Rotation of the cue card produced near-equal rotation in the preferred firing direction of head direction cells, with minimal changes in peak firing rate, directional firing range, or asymmetry of the firing-rate/head-direction function. Card removal had no effect on peak firing rate or range of firing, but in 8/13 cells the preferred direction rotated by at least 24 degrees. Similarly, changing the shape of the environment to a rectangular or square enclosure caused the preferred firing direction to rotate by at least 48 degrees for 8/10 cells in the rectangle and 3/8 cells in the square, with minimal changes in the peak firing rate or directional firing range. Hand holding the animals and moving them around the cylinder had no effect on the preferred direction or firing range of the cell, but decreased the maximal firing rate in 7/9 cells. On 2 occasions, 2 head direction cells were recorded simultaneously. The rotation of the preferred firing direction for one cell was the same as the rotation of the preferred direction for the second cell after each environmental manipulation. These results demonstrate that specific visual cues in the environment can exert control over the preferred firing direction and indicate that head-direction cell firing is not a simple sensory response to visual cues, but rather represents more abstract information concerning the animal's spatial relationship with its environment. The constancy of the angle between the preferred firing directions of pairs of simultaneously recorded head-direction cells suggests that there is a fixed mapping of the population onto direction within the environment. Thus, environmental manipulations appear to cause only a change in the reference direction, but leave all other discharge characteristics of directional cells unchanged. In the discussion, comparisons are drawn between the responses of head direction cells and hippocampal place cells to similar environmental manipulations (Muller and Kubie, 1987), and ways in which these 2 spatial systems interact in navigation are discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2303853 TI - Suppressive control of the crustacean pyloric network by a pair of identified interneurons. I. Modulation of the motor pattern. AB - A pair of identified neuromodulatory neurons, the pyloric suppressor (PS) neurons, can individually and strongly modify the activity of the pyloric network in the stomatogastric nervous system of the lobster Homarus gammarus. The PS neurons are identified by the location of their somata in the inferior ventricular nerve, their axonal projections, and their effects on pyloric network activity in vitro. Discharge of a PS neuron evokes large EPSPs in the pyloric dilator (PD) neurons and a long-lasting cessation of rhythmic activity in the neurons that control movements of the pyloric filter: PD, lateral pyloric (LP), and pyloric (PY). This cessation of rhythmic activity can outlast by several 10s of seconds a brief discharge of PS lasting only a few seconds. The different neurons of the pyloric filter do not exhibit the same sensitivity to the suppressive effects of PS, with the LP neuron being the most sensitive. Tonic discharge in PS induces graded alterations in the pyloric pattern, depending on its firing frequency. At low (less than 5 Hz) discharge frequencies, PS provokes changes in phase relationships and duration of bursting in pyloric neurons. A slight increase in PS frequency suppresses the rhythmic activity of some pyloric neurons, resulting in a switch from a triphasic to a biphasic pattern. At higher (greater than 10 Hz) PS firing frequencies, rhythmic activity in all the pyloric neurons, including the pacemakers (PD, anterior burster), is abolished, except in cells (ventricular dilator, inferior cardiac) controlling the pyloric valve. We conclude that a central pattern generator is not only subject to activating modulatory control, but may also be the target of suppressive inputs that are themselves able to provoke functional reconfigurations of the network. PMID- 2303854 TI - Suppressive control of the crustacean pyloric network by a pair of identified interneurons. II. Modulation of neuronal properties. AB - In the lobster Homarus, the 2 identified PS neurons have a strong suppressive modulatory effect on the activity of the pyloric network in the STG (Cazalets et al., 1990). In the present paper, we consider the effects of PS on individual pyloric neurons isolated from their partners in the network by cell photoinactivation and synaptic blockade. Three types of PS action are described: (1) a transient, EPSP-mediated depolarization of the PD, VD, and AB neurons; (2) a long-lasting hyperpolarization concomitant with a loss of oscillatory properties in the PD and LP neurons; (3) a long-lasting depolarization without modification of oscillatory properties in the PY and IC neurons. The various effects of PS on isolated pyloric cells were consistent with the overall effects of PS on the intact pyloric network. PMID- 2303855 TI - Intracellular and surface acetylcholine receptors during the normal development of a frog skeletal muscle. AB - 125I-alpha-bungarotoxin (125I-alpha BT) was used to measure the pool sizes of surface and intracellular acetylcholine receptors (AChRs) in the myotomal muscle of Xenopus laevis over a developmental period (stages 23-48; 1.03-7.5 d) which ranged from initial to mature stages of neuromuscular synaptogenesis. The surface pool increased progressively throughout development. The intracellular pool increased more slowly and also underwent a transient decrease. Linear regression indicated that AChRs begin to appear intracellularly and in the surface membrane at embryonic ages of 13.2 and 18.5 hr, respectively. The findings also suggest that newly synthesized AChRs contribute much more to the intracellular pool than do AChRs internalized from the surface membrane and that the rates of supply and/or intracellular resident times of these 2 sources of intracellular AChRs change during the course of normal development. Carbamylcholine, even at concentrations 10-fold greater than needed to block completely 125I-alpha BT binding to surface AChRs, blocked specific intracellular binding by only 80%. Considered in the light of previous studies on cell cultures, these results suggest that 20% of the intracellular sites are on alpha-subunits not yet assembled into pentameric AChRs. Light microscope radioautography revealed an essentially uniform distribution of intracellular AChRs along the length of the muscle cells. It is concluded that during the normal development of Xenopus myotomal muscle the accumulation and maintenance of AChRs in the postsynaptic membrane occurs in the absence of any preferential concentration of intracellular AChRs in the subsynaptic region. PMID- 2303856 TI - Firing patterns and synaptic potentials of identified giant aspiny interneurons in the rat neostriatum. AB - Intracellular recordings were made in vivo from 9 giant aspiny neurons in the neostriatum of urethane-anesthetized rats. The cells were identified by intracellular staining with HRP or biocytin. The neurons exhibited morphological features typical of neostriatal cholinergic interneurons. Six of the cells were obtained from intact animals, while 3 were recorded from rats with ipsilateral hemidecortications. Giant aspiny neurons were characterized by their slow irregular but tonic (3-10/sec) spontaneous activity and long-duration action potentials. Examination of the underlying membrane potential trajectories during spontaneous firing revealed that individual action potentials were triggered from spontaneous small (1-5 mV) depolarizing potentials. These spontaneous potentials exhibited the voltage sensitivity of ordinary EPSPs. They were much less frequent during the 80-200 msec pause in tonic afferent input that follows the excitation evoked by cortical or thalamic stimulation, and were decreased in frequency in decorticate animals. Their rise times and half-widths matched those expected for unitary synaptic potentials placed proximally on the surface of the neurons. Low intensity stimulation of neostriatal afferents produced small short-latency EPSPs that appeared to be composed of responses identical to the spontaneous depolarizing potentials. The latencies of the EPSPs evoked from the cerebral cortex and thalamus were consistent with a monosynaptic input from both structures, but the maximal size of the EPSPs was much smaller than that evoked in spiny neurons, suggesting that a smaller number of afferent inputs make synapses with each of the aspiny cells. Giant aspiny neurons exhibited much larger input resistances and longer time constants than spiny neostriatal neurons. They also exhibited relatively linear steady-state current-voltage relationship compared to spiny projection cells. Input resistances ranged from 71 105 M omega, and time constants ranged from 17.8-28.5 msec. Analysis of the charging transients in response to current pulses yielded estimates of dendritic length of approximately 1 length constant. Repetitive firing of the neurons was limited by a powerful spike afterhyperpolarization and by a strong spike frequency adaptation. The sensitivity of the giant aspiny interneuron to a relatively small number of proximal afferent synaptic contacts, its tonic firing, and its widespread dendritic and axonal fields place it in an excellent position to act as a modulator of the excitability of neostriatal projection neurons in advance of the onset of movement-related neostriatal activity. PMID- 2303857 TI - Identification of a functional glucocorticoid response element in the phenylethanolamine N-methyltransferase promoter using fusion genes introduced into chromaffin cells in primary culture. AB - The rat gene encoding phenylethanolamine N-methyltransferase (PNMT) was cloned and a consensus sequence for a glucocorticoid response element (GRE) was found at -513 bp, 5' to the transcriptional start site. In order to define the function of this element, fusion genes containing the PNMT promoter and a chloramphenicol acetyltransferase (CAT) reporter gene were constructed. These constructs did not express after transfection into any of 7 continuous cell lines, none of which endogenously produce PNMT. A system for transfecting chromaffin cells in primary culture was therefore devised using constructs containing 200 bp of the proenkephalin (ENK) promoter, whose expression characteristics are well known. pENK beta GAL-1, containing the ENK promoter with a lac Z reporter, was introduced into these cells and beta-galactosidase activity was visualized in situ. Approximately 90% of cells transfected were chromaffin; transfection efficiency was 5%. High levels of CAT activity were measured in chromaffin cells transfected with pENKAT12, possessing a CAT reporter. In contrast to tumor cell lines, pENKAT12 induction in these cells by forskolin and phorbol esters did not require a phosphodiesterase inhibitor. In this chromaffin system, both basal and regulated expression of the PNMT fusion genes were detected. Dexamethasone (dex) induced expression of pPNMT3000 and pPNMT900, containing the putative GRE and 3000 bp or 863 bp of PNMT promoter sequence, 4- to 10-fold. Expression of pPNMT300 and pPNMT100, which lack the GRE and contain 273 bp or 99 bp of PNMT promoter sequence, was unaffected by dex. Addition of the PNMT region spanning 490 to -863 bp conferred full dex responsiveness to a thymidine kinase promoter. Deletion of the putative GRE sequence by site-directed mutagenesis abolished the dex response. These data identify the sequence at -513 bp in the rat PNMT gene as a functional, positively acting GRE. Primary cultures of bovine chromaffin cells provide a biologically relevant expression system for transcriptional studies of catecholamine genes and their related neuropeptides. PMID- 2303858 TI - Enhanced behavioral conditioning to context and impaired behavioral and neuroendocrine responses to conditioned stimuli following ceruleocortical noradrenergic lesions: support for an attentional hypothesis of central noradrenergic function. AB - This study tested the hypothesis that cortical noradrenaline (NA) depletion induced by 6-hydroxydopamine (6-OHDA) widens attentional span, impairing the acquisition of conditioning to an explicit stimulus while enhancing conditioning to contextual stimuli. Sham-operated and NA-depleted rats were exposed to pairings of an auditory (clicker) CS and (footshock) US in a distinctive environment. Half of the lesioned and half of the control animals were trained with a short trace interval between presentations of clicker and shock, and half with a long trace. Associative learning theory predicts that a long trace interval should bias intact animals towards stronger contextual conditioning and, in contrast, a short trace interval should bias controls towards stronger CS conditioning. During testing, NA-depleted animals showed impaired fear conditioning to explicit cues, compared with controls, indicated by their reduced suppression of drinking when the CS was introduced into a separate, lick-operant chamber. In contrast, the same animals exhibited enhanced fear of contextual cues, as shown by their greater preference for a "safe" environment over the one in which they were shocked. The behavioral and plasma corticosterone responses of individual animals to the CS were positively correlated in both the lesion and sham groups. Corticosterone levels corroborated the impairment in CS conditioning caused by the lesion. In contrast, behavioral and corticosterone responses to contextual stimuli were not significantly correlated in either group, and there was no enhancement of the corticosterone response to contextual stimuli in the lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303859 TI - Cell surface molecules containing N-acetylgalactosamine are associated with basket cells and neurogliaform cells in cat visual cortex. AB - In the cerebral cortex, the plant lectin Vicia villosa (VVA) selectively stains the surfaces of nonpyramidal neurons. This lectin binds specifically to alpha- and beta-linked N-acetylgalactosamine (GalNac). VVA-reactive carbohydrate is highly concentrated in layer 4 of the primary visual cortex of the cat, where it is associated exclusively with GABAergic local circuit neurons. We have studied this neuronal subset with intracellular electrophysiological recording and dye marking to identify the particular cell types expressing surface GalNac. Five different types of local circuit neurons were stained intracellularly (N = 45), but only 2 types, the columnar basket and large neurogliaform cells, were also labeled by the lectin (N = 19/45). Lectin negative types included small basket, chandelier, and large bitufted cells (26/45). Spiny stellate and pyramidal neurons were also lectin negative. Electrophysiological recordings revealed differences in the duration of action potentials in smooth versus spiny stellates but no differences between lectin-positive or -negative types. A biochemical analysis of cortical glycoproteins by SDS-PAGE and lectin blotting revealed multiple bands containing GalNac enriched in membrane fractions. These carbohydrate-containing molecules may be part of a biochemical mechanism for linking together cells with common functional properties. PMID- 2303860 TI - The role of osmotic pressure and membrane potential in K(+)-stimulated taurine release from cultured astrocytes and LRM55 cells. AB - The effects of [K+]o on taurine release from glial cells were studied with primary cultures of cerebellar astrocytes and with LRM55 cells, a continuous glial cell line. The characteristics of K(+)-stimulated taurine release were virtually identical in the 2 cell types. Both cerebellar astrocytes and LRM55 cells released taurine when stimulated with high-K+ medium prepared by isosmotically substituting KCl for NaCl, but neither cell type released taurine when stimulated with hyperosmotic high-K+ medium prepared by adding solid KCl to control medium. The membrane potential of LRM55 cells was measured by intracellular recording and was insensitive to changes in [K+]o below 20 mM. LRM55 cells released taurine when stimulated with nondepolarizing concentrations of K+ (13-22 mM) if the isosmotically prepared high-K+ medium was used, but the cells did not release taurine when treated with a depolarizing concentration of K+ (50 mM) if hyperosmotic high-K+ medium was used. The time course of K(+) stimulated taurine release was quite slow, having a time to peak of 10-15 min. Small changes (2.5-10%) in the osmolarity of the medium strongly affected taurine release by cerebellar astrocytes and LRM55 cells. K(+)-stimulated taurine release from both cell types was inhibited when the osmolarity was increased with sucrose or NaCl and was enhanced when the osmolarity was reduced. Similarly, baseline taurine release was suppressed by small elevations in osmolarity and increased by reduced osmolarity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303861 TI - Retinal graft-mediated pupillary responses in rats: restoration of a reflex function in the mature mammalian brain. AB - We have shown previously that fetal retinae transplanted to neonatal rat brains are capable of making the pretectal connections necessary for driving a pupillary reflex in response to light. At birth, the rat brain is still developing and presents a favorable environment for fiber outgrowth and synaptogenesis. A remaining question is whether such grafts will also establish functional connections within the less plastic mature brain. Fetal retinae taken from Sprague-Dawley rats at embryonic day 13 or 14 were implanted in the pretectal region of mature host rats ranging in age from 6 to 11 weeks. The contralateral host eye was removed to reduce afferent competition within the pretectum between the optic input of graft and host. The remaining host optic nerve was cut before testing to eliminate all remaining host visual input. Beginning 1 month after transplantation, the retinae were surgically exposed and illuminated. In 6 of 24 animals, illumination elicited an obvious pupilloconstriction response in the host eye. The magnitude of this graft-mediated response varied between animals. Two animals produced very brisk responses, comparable to the best results seen following transplantation into neonatal hosts. In these cases, the degree of constriction was clearly dependent on the level of graft illumination. The 4 other animals produced responses that were less brisk. All 6 animals with clear cut graft-mediated pupillary responses had well-formed grafts containing numerous rosettes and ganglion cells. In addition to these 6 animals, 9 others showed extremely small or variable pupillary changes on graft illumination. The remaining 9 animals showed no stimulus-associated pupillary activity. Grafts in this group tended to be poorly formed or were located outside the pretectal area. These results show that transplanted retinae are capable of making specific functional connections with the mature brain, since an appropriate visual reflex can be elicited by illuminating the graft in the absence of host visual input. PMID- 2303862 TI - Localization and characterization of 35S-t-butylbicyclophosphorothionate binding in rat brain: an autoradiographic study. AB - 35S-t-butylbicyclophosphorothionate (TBPS) binding to slide-mounted rat brain sections was characterized for subsequent autoradiographic analysis. Cortical brain mash slices, preincubated with EDTA to remove endogenous GABA, were used for biochemical characterization. Steady state for 35S-TBPS binding was reached by 3 hr of incubation at 22 degrees C. The association rate constant (K1) and dissociation rate constant (K2) were 0.377 min-1 microM-1 and 0.011 min-1, respectively. Dissociation was monophasic and slow (t1/2 = 80 min). The kinetically derived KD was 29.4 nM. Scatchard analysis indicated a single population of binding sites with a KD of 21.0 +/- 2.2 nM and a Bmax of 1.59 +/- 0.13 pmol/mg protein. Both picrotoxin and muscimol inhibited 35S-TBPS binding completely with IC50s of 251 +/- 13 nM and 203 +/- 41 nM and nHs of 0.98 and 1.4, respectively. The distribution of 35S-TBPS binding sites in the rat brain resembles that of other ligands that bind to GABAA receptor complex with some regionally specific differences. Regions with a high degree of 35S-TBPS binding included the inferior colliculus, medial septal nucleus, central and paracentral nuclei of the thalamus, olfactory tubercle, zona incerta, dentate gyrus, and substantia nigra. 35S-TBPS preferentially bound to the molecular vs granular layer of the cerebellum. Omission of the preincubation markedly but variably decreased 35S-TBPS binding. The greatest regional decreases occurred in areas with a high degree of GABA synthesis. In addition, 35S-TBPS binding was inhibited to different degrees in the cell layers of the cerebellum. The addition of 1 microM GABA to the incubation medium of preincubated slices also produced variable decreases in 35S-TBPS binding to cerebellar layers. These findings support previous studies that demonstrate GABAA receptor heterogeneity. Our study confirms the suitability of 35S-TBPS for use as a ligand in autoradiography and demonstrates that the distribution of 35S-TBPS binding sites is significantly influenced by the preincubation-incubation conditions used. PMID- 2303863 TI - Positron emission tomographic measurements of pulvinar activity during an attention task. AB - Positron emission tomographic scans were recorded from human subjects following an object-identification task, one version of which required attentional selection and the other version of which did not. In one experimental session, the attention-demanding displays were presented in the left visual field and the nonattention displays were presented in the right visual field. In a second session, the sides of the displays were reversed. Analysis of the scans indicated that, averaged across the 2 sessions, the pulvinar showed greater glucose uptake when it was contralateral to the display of the selective attention task than when it was contralateral to the display of the nonattention task. The pattern of the data indicated that the degree of the attention task effect on pulvinar glucose uptake may differ between the hemispheres. In view of known connections between the pulvinar and cortical areas that mediate object identification, the present finding suggests that the pulvinar operates interactively with these cortical structures when an identification process demands selective attention. PMID- 2303864 TI - A monoclonal antibody that recognizes somatic motor neurons in the mature rat nervous system. AB - In order to obtain markers selective for motor neurons, an in vitro immunization was carried out using a crude homogenate of embryonic rat ventral spinal cord. We have generated a monoclonal antibody, MO-1, that binds selectively to the cell bodies of somatic motor neurons in the brain stem and spinal cord of the adult rat nervous system. In a survey of both peripheral and central nervous systems, intense labeling by MO-1 appears exclusive to this class of cholinergic neuron. Immunoreactivity is predominantly intracellular and is detectable within the somata as well as the proximal regions of processes but is absent along fiber tracts and at neuromuscular junctions. This staining pattern indicates that MO-1 does not recognize other molecules known to be present in motor neurons, such as choline acetyltransferase, acetylcholinesterase, agrin, or the calcitonin-gene related-peptide. In the spinal cord, antibody binding begins to be detectable in motor neurons late in development, during the second postnatal week. Thus, MO-1 appears to recognize a novel cellular component that accumulates in somatic motor neurons during terminal stages of differentiation. PMID- 2303865 TI - Optokinetic stimulation increases corticotropin-releasing factor mRNA in inferior olivary neurons of rabbits. AB - Stimulus-specific changes in levels of corticotropin-releasing factor (CRF) mRNA in inferior olivary neurons were studied in unanesthetized rabbits. The possible functional importance of CRF, a neuropeptide that is expressed in all inferior olivary neurons, in cerebellar synaptic transmission was investigated in a subpopulation of inferior olivary neurons, the caudal dorsal cap. Previous studies have shown that unidirectional, binocular optokinetic stimulation increases the level of discharge in neurons located in one of the caudal dorsal caps of the inferior olive and decreases the level of discharge in neurons in the opposite dorsal cap. We investigated the influence of prolonged (1-144 hr), unidirectional, binocular, optokinetic stimulus on the levels of CRF mRNA in dorsal cap neurons, measured with the technique of hybridization histochemistry. Rabbits were placed at the center of a cylindrical optokinetic drum that rotated at a constant velocity of 5 deg/sec, stimulating one eye in the posterior-to anterior direction and the contralateral eye in the anterior-to-posterior direction. Posterior-to-anterior stimulation of the left eye evoked increased activity of inferior olivary neurons located in the right caudal dorsal cap. Conversely, anterior-to-posterior stimulation of the right eye evoked decreased activity of neurons in the left caudal dorsal cap. The levels of CRF mRNA in dorsal cap neurons that were activated by prolonged optokinetic stimulation were increased by a factor of 4 to 7 after 48 hr of stimulation and by more than a factor of 10 after 144 hr of optokinetic stimulation. These optokinetically induced increases in CRF mRNA decayed to background levels after 30 hr. Our observations implicate CRF in visual olivocerebellar function and suggest that CRF may play a role in the plastic control of eye movement mediated by the visual olivocerebellar system. PMID- 2303866 TI - Chromatic mechanisms in striate cortex of macaque. AB - We measured the responses of 305 neurons in striate cortex to moving sinusoidal gratings modulated in chromaticity and luminance about a fixed white point. Stimuli were represented in a 3-dimensional color space defined by 2 chromatic axes and a third along which luminance varied. With rare exceptions the chromatic properties of cortical neurons were well described by a linear model in which the response of a cell is proportional to the sum (for complex cells, the rectified sum) of the signals from the 3 classes of cones. For each cell there is a vector passing through the white point along which modulation gives rise to a maximal response. The elevation (theta m) and azimuth (phi m) of this vector fully describe the chromatic properties of the cell. The linear model also describes neurons in l.g.n. (Derrington et al., 1984), so most neurons in striate cortex have the same chromatic selectivity as do neurons in l.g.n. However, the distributions of preferred vectors differed in cortex and l.g.n.: Most cortical neurons preferred modulation along vectors lying close to the achromatic axis and those showing overt chromatic opponency did not fall into the clearly defined chromatic groups seen in l.g.n. The neurons most responsive to chromatic modulation (found mainly in layers IVA, IVC beta, and VI) had poor orientation selectivity, and responded to chromatic modulation of a spatially uniform field at least as well as they did to any grating. We encountered neurons with band pass spatial selectivity for chromatically modulated stimuli in layers II/III and VI. Most had complex receptive fields. Neurons in layer II/III did not fall into distinct groups according to their chromatic sensitivities, and the chromatic properties of neurons known to lie within regions rich in cytochrome oxidase appeared no different from those of neurons in the interstices. Six neurons, all of which resembled simple cells, showed unusually sharp chromatic selectivity. PMID- 2303867 TI - Multiple nicotinic acetylcholine receptor genes are expressed in goldfish retina and tectum. AB - cDNAs encoding a novel nAChR structural subunit (GFn alpha-3) and a ligand binding subunit (GF alpha-3) have been isolated from a goldfish retina cDNA library. The protein encoded by GFn alpha-3 shares 88% amino acid similarity with that encoded by GFn alpha-2, a structural subunit gene previously identified to be expressed in this system (Cauley et al., 1989). The ligand-binding subunit (GF alpha-3) is likely the goldfish homolog of the rat alpha-3 gene (Boulter et al., 1986). Northern blots and S1 protection experiments show that GFn alpha-3 and GF alpha-3 genes are expressed in retina and brain. GFn alpha-3 identifies multiple RNAs differing in their 3' untranslated regions. In situ hybridization analysis demonstrates GFn alpha-3, GFn alpha-2, and GF alpha-3 expression by cells of the retinal ganglion cell layer. Unlike GFn alpha-2 and GF alpha-3, GFn alpha-3 is expressed at highest levels by cells of the retina's inner nuclear layer. In the optic tectum, both GF alpha-3 and GFn alpha-3 genes are expressed by cells of the periventricular zone, as well as more superficial layers. These results suggest the presence of multiple nAChR systems in retina and tectum. In addition, they indicate that tectal nAChRs may arise from remote (ganglion cell) as well as local (tectal cell) synthesis. PMID- 2303868 TI - Cortical radial glia: identification in tissue culture and evidence for their transformation to astrocytes. AB - Radial glia are transiently present in the developing cerebral cortex, where they are thought to guide the migration of neurons from the proliferative zone to the forming cortical plate. To provide a framework for experimental studies of radial glia, we have defined morphological and immunocytochemical criteria to identify them in primary cultures of cortical cells obtained at embryonic day 13 in the mouse. Cortical radial glia in culture for 1-2 d resemble radial glia in vivo: they have a long, thin, unbranched process extending from one or both ends of the elongated cell body and are labeled with the monoclonal antibody RC1 but not with antibodies to glial fibrillary acidic protein (abGFAP). We tested the specificity of RC1 by double-labeling with a panel of cell-type specific antibodies, and found that it labels radial glia, astrocytes, and fibroblast-like cells, but not neurons. Fibroblasts are easily distinguished from glia by morphology and by labeling with antibodies to fibronectin. To test the hypothesis that radial glia become astrocytes when their developmental role is complete, we examined their morphological and immunocytochemical development in culture. After 3-4 d in vitro radial glia develop several branched processes; in this transitional stage they are labeled by both RC1 and abGFAP. Many radial glia lose RC1 immunoreactivity as they become increasingly branched and immunoreactive to abGFAP. In areas of the cultures that have few neurons and in cultures depleted of neurons by washing, flat, nonprocess-bearing glia predominate. These cells do not lose immunoreactivity to RC1 during the 9-d period of observation even though they acquire GFAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303869 TI - Cushing's disease: results of transsphenoidal microsurgery with emphasis on surgical failures. AB - From 1977 to 1988, 56 patients with a preoperative diagnosis of Cushing's disease were treated by transsphenoidal microsurgical exploration of the pituitary gland. In 42 patients, a discrete tumor was found and a selective adenomectomy was performed. Total hypophysectomy was performed in nine patients. In an attempt to preserve pituitary function, a technique of subtotal hypophysectomy was utilized in the remaining five patients. Regular and adequate follow-up results were obtained in 53 patients. A sustained remission was obtained in 45 of these 53 patients for a remission rate of 84.9%. Eight patients were classified as therapeutic failures. The causes for failure included: 1) invasive tumor; 2) hyperplasia mistaken for an adenoma; 3) a presumed ectopic source of adrenocorticotropic hormone; 4) misdiagnosis; 5) atypical tumor; and 6) recurrence of disease after remission. In cases of therapeutic failure, the original diagnosis of Cushing's disease must be reevaluated and treatment continued until sustained remission is achieved. Necessary measures to help avoid surgical failures and an approach for further diagnostic and therapeutic maneuvers in these cases are discussed. PMID- 2303870 TI - Posterolateral microdisectomy for cervical monoradiculopathy caused by posterolateral soft cervical disc sequestration. AB - The controversy over whether to use a posterior or anterior approach for surgical treatment of soft cervical discs is still largely unsettled. However, although the posterior approach may be underutilized, it has distinct advantages when there are specific indications. Out of a large pool of cases, 53 patients presented with acute monoradiculopathy caused by soft cervical disc herniation. In 36 of these, the disc was sequestered (nonconfined) and was posterolateral to the disc space as seen on computerized tomography-myelography. Distinct motor weakness was a common clinical finding in all 36 cases. These patients were treated by using a 2- to 3-cm skin incision for the posterolateral microsurgical approach. The extent of the lateral facetectomy depended upon the relationship between the nerve root and the disc. All fragments were lateral to the dural sac and were sequestered through the anulus fibrosus and the posterior longitudinal ligament. Sequestrations were removed under direct microscopic vision, but the disc space was not entered. Pain relief and motor-power improvement in the affected radicular distribution were immediate in all patients. Sensory deficit and residual motor loss improved dramatically with normalization at approximately 6 months. No complications occurred and the mean hospital stay was 2 days. The follow-up period varied from 4 to 42 months with a mean of 26 months. Thus far, there have been no recurrences or other associated complications. By using strict selection criteria and a microsurgical posterolateral approach with removal of the sequestered disc fragment, excellent results with normalization of the monoradiculopathy can be obtained. The ease of this technique, low risk, minimal complications, and excellent results make it an attractive alternative to the anterior approach. The clinical presentations, specific indications, surgical technique, and clinical results are discussed; and a prototype of a small cervical self-retaining retractor is described. PMID- 2303871 TI - Diagnosis and microsurgical approach to far-lateral disc herniation in the lumbar spine. AB - Lumbar-disc herniations that occur beneath or far lateral to the intervertebral facet joint are increasingly recognized as a cause of spinal nerve root compression syndromes at the upper lumbar levels. Failure to diagnose and precisely localize these herniations can lead to unsuccessful surgical exploration or exploration of the incorrect interspace. If these herniations are diagnosed, they often cannot be adequately exposed through the typical midline hemilaminectomy approach. Many authors have advocated a partial or complete unilateral facetectomy to expose these herniations, which can lead to vertebral instability or contribute to continued postoperative back pain. The authors present a series of 25 patients who were diagnosed as having far lateral lumbar disc herniations and underwent paramedian microsurgical lumbar-disc excision. Twelve of these were at the L4-5 level, six at the L5-S1 level, and seven at the L3-4 level. In these cases, myelography is uniformly normal and high-quality magnetic resonance images may not be helpful. High-resolution computerized tomography (CT) appears to be the best study, but even this may be negative unless enhanced by performing CT-discography. Discography with enhanced CT is ideally suited to precisely diagnose and localize these far-lateral herniations. The paramedian muscle splitting microsurgical approach was found to be the most direct and favorable anatomical route to herniations lateral to the neural foramen. With this approach, there is no facet destruction and postoperative pain is minimal. Patients were typically discharged on the 3rd or 4th postoperative day. The clinical and radiographic characteristics of far-lateral lumbar-disc herniations are reviewed and the paramedian microsurgical approach is discussed. PMID- 2303872 TI - Correlation of motor cortex brain mapping data with magnetic resonance imaging. AB - Brain maps derived intraoperatively from patients undergoing tumor resection were correlated retrospectively with magnetic resonance (MR) images with respect to the precise localization of the motor cortex in an attempt to identify useful preoperative MR imaging landmarks that correspond to functional brain regions. Superior axial T2-weighted MR images consistently localized the central sulcus, whereas parasagittal and farlateral sagittal images readily identified the rolandic (sensorimotor) cortex, as a functional unit, based on the cingulate marginal sulcus and insula, respectively. It is therefore concluded that multiplanar MR images may serve as a useful preoperative planning aid prior to removing intrinsic brain tumors within or adjacent to the motor cortex. PMID- 2303873 TI - Effects of intrathecal baclofen on voluntary motor control in spastic paresis. AB - Intrathecal baclofen injections were given to six patients with long-standing spastic paresis resistant to any nondestructive treatment, including oral baclofen. Attempts by the patients at voluntary muscle activation before intrathecal administration of baclofen led to considerable uncontrolled coactivation of antagonist and distant muscles. After the injection, dramatic suppression of the spastic signs was accompanied by more selective voluntary muscle activation. Tonic coactivation of the antagonists and distant muscle groups during voluntary contractions was decreased while the agonist level on electromyography (EMG) was not affected (three cases) or only slightly reduced (three cases). Furthermore, in one patient with sufficient residual motor control function, there was a considerable increase in the speed of fast isotonic movements, accompanied by the emergence of the ability to generate phasic muscle bursts on EMG that were characteristic of normal motor patterns. The results suggest that baclofen exerts different effects upon reflex pathways and descending motor pathways. This therapy appears to be a promising way for improving residual motor control in patients with increased muscle tone and/or reflexes. PMID- 2303874 TI - Chronic intrathecal baclofen administration for control of severe spasticity. AB - Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use. PMID- 2303875 TI - Cryptic vascular malformations of the spinal cord: diagnosis by magnetic resonance imaging and outcome of surgery. AB - The cases of seven patients with intramedullary, cryptic vascular malformations of the spinal cord are reported. In all patients, the clinical course was progressive; a Brown-Sequard syndrome was the most common presenting symptom complex. Magnetic resonance (MR) imaging was performed in all patients. The pattern seen most often was a focus of high signal (on both T1- and T2-weighted MR images) surrounded by a larger zone of low signal (best seen on T2-weighted images), and was remarkably similar for all patients. Six patients underwent surgical exploration; removal of the lesions halted the progression of symptoms in five patients, and one patient had worsened sensory function after surgery. Motor function did not decrease postoperatively in any patient. The one patient who refused surgery has continued to decline neurologically. Histopathological examination of surgical specimens showed a cavernous malformation in one patient, a venous malformation in one, venous varices in two, and organizing hematomas in two; these findings are markedly different from those in previously reported cases of cryptic vascular malformations. PMID- 2303876 TI - Infratentorial ependymomas in childhood: prognostic factors and treatment. AB - The prognostic factors and survival data were analyzed for 35 children (aged under 16 years at diagnosis) with childhood infatentorial ependymomas treated surgically at The Hospital for Sick Children in Toronto during the years 1970 to 1987. Tumor histology was reviewed individually and grouped into three categories (Categories I to III) for survival analysis. An overall 5-year survival rate of 44.6% was obtained after the exclusion of perioperative mortality. Factors associated with an improved 5-year survival rate were: total tumor removal, noninvasive tumors, Category I histology, age greater than 6 years, and absent physical signs of parenchymal invasion or lower cranial nerve involvement. The 5 year survival rate was lower when associated with Category III histology, brain stem or cranial nerve signs, age less than 2 years, tumor invasion and/or cranial nerve involvement, and subtotal tumor removal. Clinical evidence of spinal metastases was found to be uncommon (3.1%). Surgical excision followed by radiation therapy was the primary mode of treatment for these tumors. Different approaches regarding the volume of radiotherapy to be delivered and the use of adjuvant chemotherapy are discussed. PMID- 2303877 TI - Direct approach to arteriovenous malformations in functional areas of the cerebral hemisphere. AB - The natural history of patients with arteriovenous malformations (AVM's) suggests that serious morbidity associated with AVM's in functional areas is likely to be much greater than in silent areas. Various modes of treatment of AVM's in functional areas, including direct surgical intervention, embolization, and irradiation, have been considered to carry high risks. The authors advocate direct surgical intervention to these AVM's via a microsurgical technique based on knowledge of the hemodynamic anatomy of AVM's. The technique is designed to circumscribe the AVM without removing any surrounding cortical tissue or white matter and to preserve microcirculation in the functional area. Controlled hypotension (mean arterial blood pressure 40 to 60 mm Hg) is appropriate to enhance the safety of surgical procedures without causing metabolic and electrophysiological dysfunction. Another means to prevent neurological complications is multi-staged resection of larger AVM's, which permits obliteration compartment by compartment. This technique has the advantage of maintaining circulatory sufficiency in the functional area. There was no mortality among 56 patients who underwent the surgical procedure described. Of those, 55 patients resumed their preoperative occupation and one patient became self-sufficient. PMID- 2303878 TI - Prediction of stability of cervical spine fracture managed in the halo vest and indications for surgical intervention. AB - A retrospective study was made of 173 cases of acute cervical spine injury with halo vest management to compare initial injury features with outcome. The object was to determine whether a mathematical model could be developed enabling a prediction to be made at the time of the initial assessment as to the probability of success or failure of conservative management using the halo vest alone, and thus perhaps avoid lengthy, unsuccessful treatment. Patients with facet joint dislocation were found to form a distinct subgroup of the injury population. Of the 70 patients in this subgroup, 44% achieved stability with the halo vest alone, but half of these had a "poor anatomical result." No mathematical model or associated injury features could be found to assist in the outcome prediction in this subgroup. Of the 103 patients without facet joint dislocation, 70% achieved stability with the vest alone and over 75% of these had a "good anatomical result." A useful model of outcome prediction was found for this subgroup by logistic regression analysis; the two most important predictors in the model were the amount of subluxation and the degree of angulation in the sagittal plane. PMID- 2303879 TI - Three-dimensional magnetic resonance images of the brain: application to neurosurgical planning. AB - Data from single 10-minute magnetic resonance scans were used to create three dimensional (3-D) views of the surfaces of the brain and skin of 12 patients. In each case, these views were used to make a preoperative assessment of the relationship of lesions to brain surface structures associated with movement, sensation, hearing, and speech. Interactive software was written so that the user could "slice" through the 3-D computer model and inspect cross-sectional images at any level. A surgery simulation program was written so that surgeons were able to "rehearse" craniotomies on 3-D computer models before performing the actual operations. In each case, the qualitative accuracy of the 3-D views was confirmed by intraoperative inspection of the brain surface and by intraoperative electrophysiological mapping, when available. PMID- 2303880 TI - Identical embryopathogenesis for exencephaly and myeloschisis: an experimental study. AB - Extensive histological and immunohistochemical studies were performed to elucidate the histopathogenesis of exencephaly induced in chick embryo as an experimental model. The findings were compared with those identified in a chick myeloschisis experimental model and in human autopsy cases. The experimental model of exencephaly in chick embryos was developed by induction with various teratogens including ethylnitrosourea, salicylate, and phenytoin. None of the cases of exencephaly was exposed to a teratogen prior to or within Hamburger and Hamilton stage 12 (45 to 49 hours postincubation), when the anterior neuropore closes. The process of overgrowth in development of exencephaly was identical to that of myeloschisis, and the results suggested neuronal overmaturation in the histological and immunohistochemical studies. Although the late-stage degenerative change with neovascularization over the exposed neural tissue (placode) was more severe in human exencephaly, the present experimental study may suggest a possible common embryopathogenesis of dysraphism. Exencephaly should be regarded as the most severe form of cranium bifidum, as myeloschisis is in spina bifida. PMID- 2303881 TI - Evaluation of a fiberoptic intracranial pressure monitor. AB - The fiberoptic device is a relatively new type of intracranial pressure (ICP) monitor which appears to offer certain advantages over conventional monitoring systems, particularly its ability to measure brain parenchymal pressures. This study was undertaken to analyze the accuracy and drift characteristics of the fiberoptic device and to compare pressures in the subdural, intraparenchymal, and intraventricular compartments. The device was accurate to +/- 3 mm Hg over a 0- to 30-mm Hg range in vitro. The maximum daily drift was +/- 2.5 mm Hg, with an average daily drift of +/- 0.6 mm Hg and an average drift over a 5-day period of +/- 2.1 mm Hg. In vivo, the pressures and waveform characteristics obtained with the fiberoptic device and with a strain-gauge transducer connected to a ventriculostomy were very similar. Alterations in ICP were induced by various therapeutic and pathological manipulations, and the pressures in the three intracranial compartments were compared. Changes in ICP appeared to be reflected simultaneously and equally in all three compartments. Furthermore, changes in ICP secondary to a unilateral mass lesion were identical in both supratentorial parenchymal compartments when measured simultaneously. It is concluded that the fiberoptic device is an accurate and reliable system for ICP monitoring; the pressures recorded in the subdural, intraparenchymal, and intraventricular compartments paralleled each other in all of the physiological and pathological states tested. Although the drift associated with this device is less than that reported for previously available systems, its maximal cumulative drift over a 5 day period of +/- 6 mm Hg is significant. Since the fiberoptic device cannot be recalibrated in situ, it is suggested that the device be replaced if monitoring is to be continued for periods longer than 5 days. PMID- 2303882 TI - Type I fractures of the odontoid process: implications for atlanto-occipital instability. Case report. AB - Only four cases of Type I odontoid fracture have been previously described in the English literature. Most authors consider this lesion to be stable, although the mechanism(s) of injury has not been clearly elucidated. A case of Type I odontoid fracture in association with atlanto-occipital and atlantoaxial dislocation resulting in death is presented. The normal ligamentous anatomy is reviewed and proposed mechanisms for this injury are discussed. The radiographic features of all reported cases of this type are reviewed. It is proposed that the Type I odontoid fracture is a likely manifestation of atlanto-occipital instability and rarely occurs as an isolated or stable injury. PMID- 2303883 TI - Foramen magnum meningioma: transoral resection with a bone baffle to prevent CSF leakage. Case report. AB - A case of meningioma situated at the anterior rim of the foramen magnum with successful removal via a transoral approach is reported. A new technique of preventing cerebrospinal fluid leakage is described utilizing fascia lata and a bone baffle without any attempt to close the dura, either by primary suture or tissue sealants. PMID- 2303884 TI - Stretch palsy of the spinal accessory nerve. Case report. AB - Although sharp and blunt injury to the spinal accessory nerve has been well documented, stretch or traction-type injury has not been reported previously. Such a case, treated successfully with nerve grafting, is described. PMID- 2303885 TI - Radiation-induced bilateral cystic temporal lobe necrosis: reversal of memory deficit after fenestration and internal shunting. Case report. AB - The authors report a case in which bilateral cystic temporal lobe necrosis developed after treatment of nasopharyngeal lymphoepithelioma with 7000 cGy of external beam radiation. The patient presented with an isolated memory deficit that was documented by neuropsychological testing. After fenestration and internal shunting of both cysts, there was striking resolution of the lesions and of the memory deficit. PMID- 2303886 TI - Osteolytic skull lesions secondary to trauma. Report of two cases. AB - Two patients with posttraumatic osteolytic skull lesions are presented and discussed. One was operated on, and pathological examination confirmed an inflammatory reactive process within the bone lesion. PMID- 2303887 TI - Modulation of blood flow following excision of a high-flow cerebral arteriovenous malformation. Case report. AB - The authors present a case in which a large high-flow arteriovenous malformation was totally excised. The success of the operation was in part attributed to the prevention of hyperperfusion breakthrough phenomena by the use of Selverstone clamps on the cervical carotid artery. Monitoring of cortical blood flow during surgery was found to be helpful. PMID- 2303888 TI - The versatile frontal sinus approach to the floor of the anterior cranial fossa. Technical note. AB - A technique to expose the anterior cranial base is described with entry through the anterior and posterior walls of the frontal sinus. Burr holes are avoided in the visible portion of the forehead. Expansion of the operative field may be accomplished, if necessary, by supplemental superior frontal or supraorbital rim osteotomy. The technique is rapid, safe, and provides excellent operative exposure and superior cosmetic results. PMID- 2303889 TI - Foramen magnum decompression in infants with homozygous achondroplasia. PMID- 2303890 TI - Vascularized fibular grafts for vertebral body replacement. PMID- 2303891 TI - A participative approach to administrative reorganization. AB - A participative approach to nursing reorganization proved very successful in gaining support and acceptance of major structural changes by all affected managers. In this approach, managers developed a new organizational design which better met the Nursing Division's needs while supporting its philosophy and values. Working from the design, the entire management group developed operational descriptions of each new and revised role which have proved invaluable as guidelines for people learning new interrelationships. PMID- 2303892 TI - Pastoral care: the chaplain's perspective. AB - Many nurse administrators supervise the pastoral care department. The author discusses expectations which pastoral care clergy have of nurse administrators; budget information which pastoral care department heads need in order to manage their departments; relationships between social workers and clergy; and criteria for selecting a pastoral care department head. PMID- 2303893 TI - Pastoral care: the chief nursing officer's perspective. PMID- 2303894 TI - Union dynamics in nursing. AB - Predictions of union growth among registered nurses may very well depend on hospital and nursing management's response to nurses' dissatisfaction with conditions of employment. The authors discuss federal regulations and other factors which are shaping unionization in nursing. PMID- 2303895 TI - Information systems technology: barriers and challenges to implementation. AB - Nurses, like other professionals, manage massive amounts of information. Without adequate means to process that data, neither the profession, the industry, nor the public will achieve all the benefits of contemporary health care. The authors highlight barriers to and strategies for increasing the use and effectiveness of health care information systems. PMID- 2303896 TI - Nursing information systems. PMID- 2303897 TI - Key nursing legislation passed. PMID- 2303898 TI - Dear nurse executive.... PMID- 2303899 TI - An innovative strategy leads to funding. PMID- 2303900 TI - A micro-sample critical point drying device for small SEM and TEM specimens. PMID- 2303901 TI - A high resolution SE-I SEM assessment of diimidoester fixed chimpanzee sperm. PMID- 2303902 TI - More voices for educational innovation. PMID- 2303903 TI - Gynecological and childbearing needs of lesbians. AB - This descriptive study explored how self-identification as lesbian ("coming out") affected gynecological and childbearing needs and experiences. Twenty interviews were conducted using a researcher-designed interview schedule. The majority of lesbians disclosed their sexual/affectional identity to providers ostensibly to negate heterosexual assumptions. Fear and the unpleasantness of coming out influenced the majority to postpone gynecological care or to seek lesbian sensitive providers. Half of the participants had gone to ob/gyn appointments accompanied by the partner. Traditional health history questions about marital status, sexual activity, and birth control elicited inaccurate information from participants. Participants believed important qualities in providers to be: sensitivity, knowledge about lesbian sexuality, and female gender. Providers need to learn clues of lesbian identification or coming out; they should also strive to use inclusive gender words and remove heterosexual assumptions. Seventy percent of participants desired children; alternative insemination was an accepted method of conception to most. Midwives can play a special role with lesbians desiring pregnancy and children. PMID- 2303904 TI - Long-term breastfeeding. The secret bond. AB - More and more women are choosing to breastfeed their infants, and some women choose to breastfeed for several years. The purpose of this qualitative research was to explore and describe the feelings, concerns, conflicts, and relations of 12 women who breastfed their infants for more than one year. Data collection involved semistructured, in-depth interviews; data analysis was by the grounded theory method. "Synchronization" and "reorientation" were revealed by data analysis to be key processes that explained the mothers' feelings and behaviors. Synchronization is a process in which the mother moves in pace with her child. Reorientation is a process in which the mother rearranges her lifestyle to focus on the child and his or her needs. As these two processes evolve, the mother develops a secret bond with her child to limit intrusion into their relationship. Phases of these processes are presented. This research will help health-care personnel to have a better understanding of the mothers' needs, beliefs, and priorities. PMID- 2303905 TI - Premature rupture of the membranes with routine cervical exams. AB - Premature rupture of the membranes at term occurs frequently in otherwise uncomplicated pregnancies. Several theories have been postulated as to the cause of this complication, including the practice of routine prenatal cervical examinations. A randomized prospective study was done to determine if prenatal cervical exams did increase the risk of premature rupture of the membranes. Fifty six women were examined intracervically every week from 37 weeks' gestation until delivery, and 45 women received no cervical examinations until labor began. Premature rupture of the membranes occurred in ten women (18%) who were examined and in six women (13%) who were not. There was no statistically significant difference between the two groups of women, leading to the conclusion that prenatal cervical examinations do not cause an increase in the frequency of premature rupture of the membranes. PMID- 2303906 TI - Rendezvous in Rhamu. Teaching and learning with traditional birth attendants in rural Kenya. AB - When Carol Steele came to Rhamu, Kenya, in 1983 as a Quaker, Peace, and Service volunteer, there was little or no contact or cooperation between the Government Health Center personnel and the traditional birth attendants of the surrounding villages. The two groups were worlds apart in thinking, attitudes, and practices. The government center was viewed as alien by the people, with nothing to offer them except emergency care. The health center personnel viewed the traditional birth attendants as uneducated, unskilled women, who jealously kept clients away from the professional obstetric care the clinic provided. It was Carol Steele's plan to bring these diverse groups together in a professional, trusting relationship. Her success in accomplishing this task is the theme of this article. PMID- 2303907 TI - Quantitative relationship between intestinal sucrase inhibition and reduction of the glycemic response to sucrose in rats. AB - We have investigated the quantitative relationship between sucrase inhibition and reduction in the 0-3 h glycemic response to an oral dose of sucrose in rats. Castanospermine is a quasi-irreversible sucrase inhibitor that did not dissociate from sucrase during tissue preparation or assay for sucrase activity. An oral dose of castanospermine (0.1-3.0 mg/kg body wt) dose-dependently reduced sucrase activity of intestinal segments by 15-90%; 0.4 mg/kg body wt reduced total sucrase activity about 50%. The lower doses inhibited sucrase much more extensively in the proximal than in the distal segments. Castanospermine also dose-dependently reduced the 0-3 h glycemic response to sucrose; 1.5 mg/kg body wt reduced the glycemic response about 50%. Each submaximal castanospermine dose inhibited total sucrase activity more than it reduced the glycemic response. We conclude that intestinal sucrase activity in the rat is in modest excess relative to the rate-determining step of glucose absorption following sucrose administration. Fourteen days of castanospermine treatment (0.2 mg.kg body wt-1.d 1) resulted in sucrase inhibition that was similar to a single castanospermine treatment, suggesting that castanospermine treatment resulted in neither cumulative sucrase inhibition nor induction of sucrase activity. PMID- 2303908 TI - Dietary energy restriction decreases ex vivo spleen prostaglandin E2 synthesis in Emory mice. AB - Dietary energy restriction prolongs life-span and enhances immune responsiveness by mechanisms yet to be elucidated. Prostaglandin E2 (PGE2) has a suppressive effect on several parameters of cell-mediated immunity. The effect of energy restriction on splenic PGE2 synthesis in Emory mice was studied. Weanling Emory mice were fed an energy-restricted (R, 71.3 kcal/wk) or control (NR, 90.8 kcal/wk) diet for 11-14 mo. The final weights of R mice were 66% of weights of NR mice (27 +/- 1 vs. 41 +/- 1 g for females and 34 +/- 1 vs. 51 +/- 1 g for males, for R and NR, respectively). NR female mice had higher spleen PGE2 levels than NR male mice (698 +/- 64 vs. 522 +/- 47 ng/mg protein, P = 0.03). In all cases, R mice had less PGE2 than NR mice, and there was no sex-related difference in R mice (418 +/- 39 vs. 698 +/- 64 ng/mg protein in R and NR females, P = 0.001 and 416 +/- 39 vs. 522 +/- 47 ng/mg protein in R and NR males, P = .009). Total spleen PGE2 was also reduced significantly by energy restriction; however, gender differences were not observed in total spleen PGE2 level of NR mice. Thus, 1) spleens from female mice synthesize more PGE2/mg protein than do those from male mice, and 2) dietary energy restriction reduces ex vivo spleen PGE2 synthesis. This phenomenon may contribute to the observed immunostimulatory effect of dietary energy restriction in mice. PMID- 2303909 TI - Contribution of several amino acids and lactate to gluconeogenesis in hepatocytes isolated from rats fed various diets. AB - The contribution under various nutritional regimens of several amino acids and lactate to gluconeogenesis was estimated by measuring the glucose formation from 14C-labeled substrates. Isolated rat hepatocytes were incubated for 60 min in a Krebs-Ringer bicarbonate buffer pH 7.4 containing lactate, pyruvate and all the amino acids at concentrations similar to their physiological levels found in rat plasma, with one precursor labeled in each flask. In all conditions, lactate was the major glucose precursor, providing over 60% of the glucose formed. Glutamine and alanine were the major amino acid precursors of glucose, contributing 9.8% and 10.6% of the glucose formed, respectively, in hepatocytes isolated from starved rats. Serine, glycine and threonine also contributed to gluconeogenesis in the starved liver cells at 2.6, 2.1 and 3.8%, respectively, of the glucose formed. The rate of glucose formation from the isolated hepatocytes of the starved rats and those fed either high protein or high fat was higher than that from rats fed a nonpurified diet. PMID- 2303910 TI - Nomenclature policy: generic descriptors and trivial names for vitamins adn related compounds. PMID- 2303911 TI - Stimulation of energy intake and growth by saccharin in rats. AB - Rats fed wet diets containing saccharin consumed 12-14% more energy and gained 24 55% more weight than rats fed the same diets without saccharin. Saccharin-induced stimulation of intake was usually not so pronounced during the first week as during subsequent weeks of each experiment. Similar results were obtained using diets high in starch and fat. However, these effects could be obliterated by simply exposing the rats to unsweetened (plain) diet or to saccharin in water for several days before the sweetened diets were introduced. Furthermore, although stimulation of intake by saccharin was observed with diets containing 80% water, no such effect was observed with a diet containing 60% water. Rats given low energy sweetened water in addition to their 80% water diet consumed substantially more fluid but not more or less energy than rats given unsweetened water. Preference tests suggest that saccharin increases diet palatability only very slightly; this finding is one of several observations suggesting that stimulation of intake by saccharin cannot be interpreted in terms of increased diet palatability. These results suggest that dietary hyperphagia results from the interaction between innate and learned responses to the taste of foods. Osmotic factors did not seem to exert a major influence in these experiments. PMID- 2303912 TI - Dietary branched-chain amino acids and protein selection by rats. AB - Consumption by rats of high protein diets is associated with elevated plasma and brain concentrations of branched-chain amino acids (BCAA). We examined the possibility that changes in BCAA concentrations in blood and brain might serve as modulators of protein consumption. After young rats had adjusted to selecting between a 10% or 25% casein diet and a 50% casein diet, a mixture of BCAA was included in the diet containing the lower amount of protein (10% + BCAA, 25% + BCAA). Supplementation of the 10% or 25% casein diets with BCAA and subsequent elevation of BCAA concentrations in plasma and brain were associated with increased selection of protein in rats given the 10% + BCAA/50% casein diet choice, but not in rats offered the 25% + BCAA/50% casein diets. When no alternative diet was available, addition of BCAA to a 15% casein diet depressed food intake, and rats given a choice between a 15% casein diet with or without added BCAA selected almost exclusively the diet without added BCAA. Although BCAA concentrations were high in plasma and brain in all experiments, concentrations of methionine, tyrosine, phenylalanine, tryptophan and histidine were low in brain in experiments in which rats altered their diet or protein selection after BCAA addition. High concentrations of BCAA in plasma and brain were not consistently associated with changes in protein selection. PMID- 2303913 TI - Nitrous oxide provokes changes in folylpenta- and hexaglutamates. AB - Liver folates isolated from rats fed a control diet consisted of H4PteGlu5 (44% of total) and 5-methyl-H4PteGlu5 (19%) with smaller amounts of 10-formyl H4PteGlu5 (13%), H4PteGlu6 (13%), 10-formyl-H4PteGlu6 (4%) and 5-methyl-H4PteGlu6 (2%). Folates from methionine-deficient rats contained more nearly equal amounts, on a molar basis, of folylpenta- and hexaglutamates, and hence these were more suitable subjects for comparing the metabolism of these compounds in vivo. Livers from methionine-deficient rats contained H4PteGlu5 (30%), 5-methyl-H4PteGlu5 (13%), 10-formyl-H4PteGlu5 (10%), H4PteGlu6 (22%), 5-methyl-H4PteGlu6 (9%) and 10 formyl-H4PteGlu6 (11%). With exposure to N2O, 5-methyl-H4PteGlu5 and 6 increased to 27% and 13%, respectively, whereas H4PteGlu5 and 6 decreased to 20% and 17%, respectively. Nitrous oxide (N2O) perturbed both the penta- and hexaglutamates; the effect was somewhat more pronounced with the pentaglutamates. The partial depletion in tissue H4PteGlun with N2O treatment helps explain the concomitant inhibition of the oxidation of [ring-14C]histidine, an event dependent on tetrahydrofolates. PMID- 2303914 TI - The metabolism of [14C]beta-carotene and the presence of other carotenoids in rats and monkeys. AB - The metabolism of beta-carotene has been studied in both rats and Rhesus monkeys, following the oral administration of [14C]beta-carotene in olive oil supplemented with 1 mg/mL alpha-tocopherol. In the rats, peak serum accumulation of [14C]retinol occurred 4 h after a single oral dose, but we were not able to detect [14C]beta-carotene in rat sera at any time up to 72 h after dosing. Small amounts of [14C]beta-carotene were found in the livers, although 88-94% of the recovered radioactivity was localized in the retinol fraction after saponification. Although radioactivity was also found in fractions other than beta-carotene and retinol, the amounts were too small to allow characterization. In the monkeys, peak accumulation of [14C]retinol in serum occurred between 8 and 24 h after supplementation. Some [14C]beta-carotene was also present. Most of the absorbed radioactivity was stored in the liver as [14C]retinol, although 2-8% was present as [14C]beta-carotene. Other organs also contained [14C]beta-carotene, confirming the ability of the monkey to absorb intact beta-carotene. In addition, monkey livers and other organs were found to contain lutein, zeaxanthin, alpha cryptoxanthin, beta-cryptoxanthin and beta-carotene, presumably arising from dietary sources. PMID- 2303915 TI - Copper-deficient mice have higher cardiac norepinephrine turnover. AB - Norepinephrine metabolism was investigated in 6-wk-old male Swiss albino copper deficient and copper-supplemented mice. Beginning 4 d after birth of pups, dams were fed a diet low in copper (Cu) (0.4 mg/kg) and offspring were weaned to this diet at 21 d of age. Half the dams and their respective offspring received Cu (20 micrograms/ml) in the drinking water (+Cu) and served as controls. Unsupplemented offspring (-Cu) had lower liver Cu levels, exhibited anemia, and had increased heart weights but normal body weights compared to +Cu mice. Urinary output of norepinephrine and dopamine was higher, whereas output of creatinine and epinephrine was not different in -Cu mice compared to +Cu mice. Both fractional and calculated turnover of norepinephrine following inhibition of tyrosine 3 monooxygenase by alpha-methyl-p-DL-tyrosine methyl ester (alpha-MT) was higher in hearts from -Cu mice than in those from +Cu mice. Hearts and spleens from -Cu mice appeared to have higher tyrosine 3-monooxygenase activity as judged by increasing rates of L-dihydroxyphenylalanine accumulation following injection of m-hydroxybenzylhydrazine (NSD-1015), an inhibitor of aromatic amino acid decarboxylase. Turnover rates of norepinephrine for cerebellum were not different between +Cu and -Cu mice. Loss of norepinephrine from adrenal glands of mice injected with alpha-MT was not observed in the 8-h period studied. The smaller norepinephrine pool observed in organs of -Cu mice may have resulted from lower synthesis due to limiting dopamine-beta-monooxygenase activity and to higher turnover. PMID- 2303916 TI - Dietary supplements of vitamin E, beta-carotene, coenzyme Q10 and selenium protect tissues against lipid peroxidation in rat tissue slices. AB - A tissue slice model was employed to assess the effects of dietary antioxidant supplements on lipid peroxidation. In one experiment, rats were fed diets containing, either alone or in combination, vitamin E, selenium, beta-carotene or coenzyme Q10 for 42 d, and the extent of spontaneous and induced lipid peroxidation was determined by release of thiobarbituric acid-reactive substances (TBARS) into the medium. Vitamin E exhibited the greatest protection against lipid peroxidation in liver, heart and spleen; in kidney, selenium was most protective. Coenzyme Q10 was active against lipid peroxidation induced by tertbutyl hydroperoxide (t-BHP). In a second experiment, rats were fed diets containing varying amounts of vitamin E, selenium, beta-carotene and coenzyme Q10 for 30 d. Spontaneous lipid peroxidation in liver, kidney and heart decreased with increasing levels of dietary antioxidants. With increasing amounts of antioxidants, there was a diminution in TBARS released by liver and kidney slices incubated with t-BHP; in heart, only the highest levels of antioxidants significantly decreased production of TBARS. Inverse correlations between dietary vitamin E and TBARS, tissue vitamin E and TBARS, and tissue selenium-glutathione peroxidase and TBARS were highly significant. The procedure used here can evaluate dietary supplements that may find practical applications in decreasing the oxidant radical portion of disease processes. PMID- 2303917 TI - Outcomes of AIDS training for supervisory and nonsupervisory personnel in the workplace. AB - Dealing with AIDS in the workplace is complicated by a variety of complex issues. One factor influencing how AIDS is dealt with is the difference in knowledge and attitudes between supervisory and nonsupervisory personnel. We surveyed 3834 supervisory and nonsupervisory personnel from a number of businesses and corporations in the Louisville metropolitan area. The differences found in this study suggest strategies for training to address the problem of AIDS in the workplace. PMID- 2303918 TI - Morbidity of pulmonary tuberculosis among silicotic and nonsilicotic foundry workers in Denmark. AB - Increased tuberculosis risk associated with silicosis is well described. The present study defines the incidence of pulmonary tuberculosis among 5424 nonsilicotic and 155 silicotic male foundry workers observed between 1967 and 1986. For the 18-year follow-up period, the following groups had statistically significant increased standard incidence rates (SIR) for pulmonary tuberculosis: silicotics, SIR = 1000 (95% CI = 272 to 2561, P less than .01); nonsilicotics employed at least 25 years, SIR = 353 (95% CI = 130 to 768, P less than .01); and for the entire cohort, SIR = 201 (95% CI = 125 to 397, P = .01). These results suggest that silica exposure may cause an increased pulmonary tuberculosis risk among nonsilicotic foundry workers. PMID- 2303919 TI - Silica exposure and tuberculosis: an old problem with some new twists. PMID- 2303920 TI - Injuries and illnesses aboard research vessels of the University National Oceanographic Laboratory System. AB - The University National Oceanographic System operates a fleet of vessels to carry out its scientific projects. Illnesses and injuries at sea are handled by first responders aboard the vessels in consultation with land-based physicians at a telecommunications response center in the United States. During the period 1985 to 1987, 122 cases among regular and scientific crew required medical consultation by telecommunications. Of these, 31% were injuries, 34% were medical cases (infected), 12% were sexually transmitted diseases, and 23% were medical cases (noninfected). Evacuation from the vessel, vessel diversion, or repatriation of the patient was required for 20% of all cases; of these, 48% were for injuries, 36% for noninfected medical illnesses, and 16% for infected medical cases. Rates of illness and injury were calculated using the crew days at sea as a denominator. PMID- 2303921 TI - Filling the void of well-trained occupational medicine physicians: a challenge for the 1990s. AB - Occupational Medicine is a vibrant, rapidly expanding medical specialty. Many reports and studies have emphasized the increasing demand for occupational medicine physicians. Unfortunately, a lack of knowledge regarding the field among the general public and within the medical community as well functions as a major stumbling block to the growth of our profession. Occupational medicine needs to attract young physicians into accredited training programs. Assuring that these programs exist, are properly funded, and provide quality training are, of course, important first steps. The efforts of the Accreditation Council for Graduate Medical Education, which provides residency accreditation, and the American College of Occupational Medicine (ACOM), which administers the Occupational Physicians Scholarship Fund, are significant and essential. It is equally vital, however, that there be a pool of qualified applicants for these training positions. We address the issue of attracting physicians to accredited occupational medicine training programs and offer several practical recommendations to help achieve this goal. PMID- 2303922 TI - Assessment of colorectal cancer incidence among polypropylene pilot plant employees. AB - Our recent study reported a colorectal cancer excess among workers involved in the manufacture of polypropylene. To follow up on this finding, we initiated a study of colorectal cancer incidence among polypropylene pilot plant workers within the same company. The purpose of this investigation was to determine whether colorectal cancer incidence was elevated among workers who may have had exposures similar to those experienced on the commercial production unit. The study population included 183 employees who worked at least 6 months on either of two pilot plants. Overall, there were three observed colorectal cases v. 3.3 expected (standardized incidence ratio = 0.9, 90% confidence interval 0.3 to 2.3). Analyses for the process, mechanic, and laboratory subgroup showed rates consistent with expected values (3 observed, 2.8 expected; standardized incidence ratio = 1.1, 90% confidence interval 0.3 to 2.8). Analyses by duration of employment and latency did not show patterns consistent with the colorectal cancer excess previously reported. The likelihood of lower or different exposures on the pilot plant than would be found on commercial production units is discussed along with the need for studies of workers in other polypropylene manufacturing environments. PMID- 2303923 TI - Ergonomic deficiencies: II. Probable causes. AB - This is Part II of a three-part series that examines various aspects of ergonomic deficiencies at work. Part I examined pain at work and the association between such pain or discomfort and a poorly designed workplace or poorly structured job. Part II considers causes of ergonomic deficiencies and their identification and assessment through the use of checklists. Part III demonstrates that treating the symptoms or apparent proximate causes does not assure correction of the root causes, and suggests strategies for correcting ergonomic deficiencies. PMID- 2303924 TI - Fieldworker exposure to pesticides. PMID- 2303925 TI - A study of a work site health promotion program and absenteeism. AB - This paper reports on a study of the absenteeism experience of two groups of Johnson & Johnson employees over a 3-year period. Employees at four company sites (n = 1406) where LIVE FOR LIFE, a comprehensive health promotion program, had been introduced, were compared with employees at five company sites (n = 487) without the health promotion program. Analyses of covariance were employed to control for differences between the two study groups with respect to age, gender, job classification (wage or salaried), as well as baseline levels of absenteeism. Adjusted mean levels of absenteeism among wage earners in the LIVE FOR LIFE groups were found to decline over the study period, and were significantly lower (P less than .01) than mean levels for the non-LIVE FOR LIFE wage employees in the final year of the study. No significant differences were found for salaried personnel. PMID- 2303926 TI - New challenges in resident education. Symposium of the Society of General Internal Medicine. April 27-28, 1989, Arlington, Va. Proceedings. PMID- 2303927 TI - Teaching models in an ambulatory training program. AB - Ambulatory care training is increasingly important in internal medicine. Such training centers on the practice where residents and faculty see their patients; thus, features of the practice model influence what residents learn. A resident faculty group practice affiliated with a division of general internal medicine has many advantages. In such a practice, learning centers on resident-patient interactions, around which a comprehensive teaching program must be built. Major features of such a program include the mentoring of residents by faculty who work with them longitudinally and the presence of a well-balanced structured curriculum addressing clinical and nonclinical topics related to patient care. Teaching residents to interact and communicate with patients is crucial; approaches include role-modeling by faculty, use of videotaping, and role-playing and other innovative methods. Feedback is integral to learning and helps shape the attitudes and values that permeate residents' practices. PMID- 2303928 TI - Teaching residents to care for vulnerable populations in the outpatient setting. AB - Residency programs have an obligation to teach house officers to care for vulnerable populations. Such populations consist of those whom physicians tend to consider undersirable as patients, and thus who often lack adequate care, because they cannot pay for medical services, because they have medical problems that are difficult to manage, or because they have characteristics giving them low social status. The authors identify and discuss key aspects of learning to care for such populations. These aspects include obtaining appropriate experience caring for disadvantaged patients, developing sensitivity to pertinent sociocultural issues, exploring biases, acquiring relevant special skills, studying epidemiology of diseases in specific vulnerable groups, and learning about health care financing and health policy. Measures to help residents obtain more satisfaction from caring for vulnerable patients are among additional topics discussed. PMID- 2303929 TI - Curriculum for ambulatory care training in medical residency: rationale, attitudes, and generic proficiencies. AB - This paper provides a foundation for establishing curricula to train medical residents in ambulatory care. To do so, it first presents reasons that curricula are needed in this area. It then delineates attitudes and proficiencies (knowledge and skills) that such curricula should be designed to instill. Finally, it briefly discusses implications for curriculum development. Extensive tables are provided, including detailed lists of generic proficiencies that residents should attain. Among realms in which these proficiencies lie are organizing the ambulatory care encounter, using interpersonal skills, gathering information through physical examination and other means, obtaining and employing clinically useful knowledge, documenting the encounter, and planning and coordinating care. The paper notes that planning for the discharge of patients from the hospital can contribute to obtaining proficiencies important in ambulatory care. PMID- 2303930 TI - Ambulatory medical education: a reconsideration of sites and teachers. AB - This paper deals with the varied sites and teachers that can and should be used in educating residents and medical students in ambulatory care. A basic premise is that sites other than academic medical centers and teachers other than physician faculty members should be among those used. The paper describes how institutions have used non-traditional sites and teachers. Then, after emphasizing the need to choose settings according to curricular objectives, it discusses teaching sites, both hospital-based (general medical, specialty, and multidisciplinary clinics) and community-based (home care settings, rural clinics, nursing homes, and community clinics). Next it describes the array of current and potential teachers, which includes generalist and specialist physician faculty members, community physicians, residents, and allied personnel such as pharmacists and nurses. The paper also discusses forces resisting and supporting the use of new sites and teachers. It ends with general recommendations. PMID- 2303931 TI - Faculty development for ambulatory teaching. AB - This paper deals with helping faculty members and others learn to teach more effectively in ambulatory settings. First it suggests ways to help clinicians expand and update their knowledge and skills in ambulatory medicine as a foundation for teaching. Next it identifies six skills--establishing mutual expectations, setting limited teaching goals, asking questions, stimulating self directed learning, giving feedback, and capitalizing on role modeling--that are basic to effective ambulatory teaching. Then it presents strategies for developing and maintaining such skills: assessment of teaching, consultation with experts in education, and participation in programs such as workshops. The paper ends by discussing aspects of institutional support and calling for research on the impact of faculty development efforts on teaching and learning in medicine. PMID- 2303932 TI - Faculty rewards for the generalist clinician-teacher. AB - Historically, medicine has regarded itself as a profession of great breadth, encompassing the total range of human activity: biological, behavioral, social and organizational. In the last several decades, however, it has become increasingly reductionist, fragmented, and specialized. Recent developments, as exemplified by the return of the generalist clinician-educator to the academic community, portend a reversal of this trend. Manifestations of a change in the orientation of medicine and medical education toward bolism and bumanism include a movement toward improved compensation for "cognitive" services, development of new promotion tracks for clinician-teachers, and increased support and recognition of applied clinical research. Generalist faculty are in a position to benefit from these trends, but obstacles remain; vigilism and activism are required to maintain momentum. PMID- 2303933 TI - The service/education conflict in residency programs: a model for resolution. AB - Residency programs consist of a range of activities involving service to patients and education of residents. The observation that a conflict exists between the service and education components of residency is widespread and has been used to explain many of the problems afflicting such programs today. The authors believe that the service/education conflict is a significant barrier to change in residency programs. A model is presented for residency education that reorganizes the service and education components. First, they present a broad overview of the conflict. Then they provide a brief historical perspective and comment on some of the current recommendations for residency programs. Next, they discuss how principles of adult learning relate to residency and propose a new model of residency that adheres more closely to these principles. Finally, the proposed model is presented in some detail and its implications are discussed. Only if the service and education components of residency are carefully delineated can residency programs adapt to the changing and growing needs of postgraduate medical education. PMID- 2303934 TI - Studies of traumatic neuralgias in the maxillofacial region: surgical pathology and neural mechanisms. AB - Microsurgical exploration of injured trigeminal nerves in patients with neuralgia revealed four variations of traumatic neuroma, associated foreign objects, and a sprouting of nerve collaterals from adjacent uninjured nerve. A comprehensive theory of traumatic trigeminal pain is proposed based on three sites of pathosis: peripheral neuroma, somatic and autonomic collateralization, and central deafferentation pathoses. Anesthesia dolorosa is related in this model to amputation neuromas and central pathosis. Sympathetic mediated pain is attributed to autonomic C-fiber units in peripheral injured zones. Hyperalgesia is attributed to mechanosensitive A-fiber units in the nerves being linked to corresponding irritable central nervous system neurons. Hyperpathia is explained on the basis of ephaptic transmission between adjacent fibers in neuromas. PMID- 2303935 TI - Bone scanning for evaluating mandibular bone extension of oral squamous cell carcinoma. AB - Inability to control the primary tumor in oral cancer, leading to local recurrence, results in low survival rates. The extent of bone involvement is therefore a critical factor in planning treatment. To evaluate whether uptake of 99mTc-DPC (dicarboxypropane-diphosphate) was reliable in demonstrating the extent of mandibular involvement, 13 consecutive patients with squamous cell carcinoma of the mandibular gingiva, floor of the mouth, and lower buccal sulcus were studied. Bone involvement, as judged from preoperative radiographs and bone scans, was compared with that determined through careful analysis of histologic sections of jaw specimens. The bone scan findings corresponded well with the histologic findings in 10 cases. In contrast to earlier studies, there were no false-positive findings. False-negative bone scans were seen in three cases in which there was infiltration of the upper cortex of the mandible. A negative bone scan, therefore, cannot guarantee absence of bone involvement. Nevertheless, bone scanning seems to provide valuable information for preoperative evaluation of evident tumor infiltration of bone. PMID- 2303936 TI - The effect of repetitive screw hole use on the retentive strength of pretapped and self-tapped screws. AB - Multiple systems for internal screw fixation are presently in use in oral and maxillofacial surgery. These systems differ in screw diameter, material, and design. This study evaluated the uniaxial pullout strength of five screw systems. Two-millimeter, 2.7-mm, and 3.5-mm screws were initially evaluated for pullout strength. Pretapped and self-tapped screws were then inserted into the same hole multiple times before pullout testing. Results of pullout testing revealed no significant difference in pullout strength of pretapped and self-tapped screws of equal diameter (P greater than .05). Increased screw diameter produced increased pullout strength. No significant difference in pullout strength was noted in pretapped or self-tapped screws inserted into the same hole one, two, or three times before pullout testing (P greater than .05). PMID- 2303937 TI - The effects of mechanical strain on osteoblasts in vitro. AB - The effect of mechanical strain on bone is important to the field of oral and maxillofacial surgery. Oral and maxillofacial surgeons are involved on a daily basis with problems including alveolar ridge resorption, implant stability, craniofacial growth, and bone resorption related to trauma and pathology. To understand and control these effects on bone, it is important to examine the effects of mechanical strain on the osteoblasts. This series of experiments provides the changes in alkaline phosphatase, collagen synthesis, and protein synthesis in osteoblast-like cell subjected to mechanical strain. PMID- 2303938 TI - Aseptic necrosis of the mandible: report of two cases. AB - It appears that clinically significant aseptic necrosis following mandibular osteotomies is a more infrequent occurrence than that following maxillary surgery because only two cases were reported in a questionnaire dealing with major vascular complications following orthognathic surgery. Significant necrosis is unlikely to occur if a surgeon follows the basic principle of stripping the minimal amount of mucoperiosteum and muscle attachment from the osteotomized segments commensurate with the successful completion of the osteotomies. PMID- 2303939 TI - Multifocal central giant cell lesions of the maxillofacial skeleton: a case report. AB - The classification of giant cell lesions of the maxillofacial skeleton is one that remains controversial. Classifying giant cell lesions of the jaw as granulomatous based solely on location seems inappropriate. The categories of benign or malignant are more realistic. Benign lesions may then be subdivided into aggressive and nonaggressive. Multifocal giant cell lesions strongly suggest the brown tumor of hyperparathyroidism. Serum chemistry tests including calcium, phosphorus, ionized calcium, and PTH levels should routinely be obtained when a giant cell lesion is suspected. A case of benign, aggressive, multifocal central giant cell lesions of the maxillofacial skeleton, in the absence of either primary or secondary hyperparathyroidism is presented. Whether this represents metastasis from the initial lesion, metabolic osteoclastic dysfunction, or a new entity, craniofacial giant cell dysplasia, is unknown. PMID- 2303940 TI - Squamous cell carcinoma arising in a plunging ranula. AB - A case report of a 36-year-old man with a plunging ranula of 15 years' duration, in which squamous cell carcinoma arose from the cyst wall, is presented. Pathogenesis and treatment of ranulas is briefly discussed. PMID- 2303941 TI - Congenital intraoral epithelial bands: report of two cases. PMID- 2303942 TI - Pulmonary infection following exodontia in a patient with glycoprotein-180 deficiency. AB - There is a significant increase in the occurrence and severity of infection in patients with immunodeficiencies, especially after minor invasive procedures. Therefore, alternatives to invasive procedures, continual vigilance of indwelling catheters, and appropriate preoperative evaluation and management of these patients are of paramount importance. PMID- 2303943 TI - Altered-sequence Le Fort I osteotomy: pterygoid-tuberosity dysjunction. PMID- 2303944 TI - Stabilization of plating screws during placement for osseous surgery. PMID- 2303945 TI - Recommended use of Proplast. PMID- 2303946 TI - Oral cryptococcosis in AIDS patients. PMID- 2303947 TI - The name of our specialty. PMID- 2303948 TI - Cholesteatoma versus mucocele of the maxillary sinus. PMID- 2303949 TI - Excursion of the flexor digitorum profundus tendon: a kinematic study of the human and canine digits. AB - The most common problem following primary flexor tendon repair is the failure of the tendon apparatus to glide, secondary to the formation of adhesions. Early motion following tendon repair has been shown to be effective in reducing adhesions between the tendon and the surrounding sheath. Therefore, it is important to determine the amount of flexor tendon excursion along the digit during joint motion. In this study, the excursion between the flexor digitorum profundus (FDP) tendon and the sheath was examined in both human and canine digits. Based on roentgenographic measurements and joint kinematic analysis, the motion of the bones, the FDP tendon, and the sheath were measured with respect to joint rotations. It was found that the canine flexor tendon apparatus behaved similarly to that of the human for the motions studied. The amount of tendon excursion was very small in regions distal to the joint in motion (approximately 0.1 mm/10 degrees of joint rotation). There was little displacement of the sheath (0.2-0.3 mm), except at the metacarpal joint region during metacarpophalangeal (MCP) joint motion and at the proximal interphalangeal (PIP) joint region during PIP joint motion. Tendon excursion relative to the tendon sheath was the largest in zone II during PIP joint rotation (1.7 mm/10 degrees of joint rotation). These results suggest that PIP joint motion may be most effective in reducing adhesions following tendon repair in zone II. PMID- 2303950 TI - Resistance of a defect of the supraspinatus tendon to intraarticular hydrodynamic pressure: an experimental study on rabbits. AB - The healing of a standardized defect of the supraspinatus tendon in a time related series on rabbits was monitored with arthrography and simultaneous determination of the intra-articular hydrodynamic pressure of the glenohumeral joint. All normal glenohumeral joints produced a biphasic pressure versus volume curve. Rupture of a normal glenohumeral joint occurred at a pressure level of 140 170 mm Hg and was located in the area around the biceps tendon sheath. In joints with a defect of the supraspinatus tendon, leakage of the contrast medium was evident up to the sixth week, at an intra-articular pressure varying from 40 to 100 mm Hg. After week 6, no leakage of the cuff was seen during the determination of the intraarticular pressure. This was in accordance with the histological findings: the defect was covered with solid scar tissue from the ninth week onward. Resistance to hydrodynamic intraarticular pressure proved a reliable method of determining the strength of the healing of the supraspinal defects. PMID- 2303951 TI - The interrelation of fiber bundles in the anterior cruciate ligament. AB - The anterior cruciate ligaments (ACL) of dogs, humans, and rabbits were studied by light and scanning electron microscopy after fixation in situ. In all species, the ACL was composed of multiple 20 microns-wide collagen fiber bundles separated by columns of cells in fibrous capsules. These bundles were in turn grouped into fascicles of varied size. The fascicles were surrounded by thin membranous sheets that ran through the ligament forming single or multiple layers between fascicles. Splaying of the ACL at insertion was created by increased volume in the cellular intervals. Bending of the fiber bundles occurred in this region- which corresponds to the fibrocartilaginous zone. We propose that the cell layers accommodate compressive forces and the membranes allow slipping among fascicles without compromising blood supply. PMID- 2303952 TI - Comparison of the effects of adriamycin and methotrexate on orthotopic and induced heterotopic bone in rats. AB - The effect of the two antineoplastic drugs, Adriamycin and methotrexate, on orthotopic bone, and on the induction of experimental heterotopic bone in rats was analyzed. The drugs were administered as single injections: Adriamycin in s.c. doses of 0.5 and 2 mg/kg body weight and methotrexate i.v. 100 and 250 mg/kg body weight followed by leucovorin rescue after 2 h. A passing, but significant, decrease in body weights occurred in the methotrexate-treated animals, but not in those given Adriamycin. Analysis of the amount of heterotopic bone formed 4 weeks after induction by demineralized bone matrix revealed a 30-40% decrease in the groups treated with either of the antineoplastic agents, whereas orthotopic bone was unaffected. Six weeks after the treatment the net effect on the induced bone had decreased. The present study shows that the two antineoplastic drugs Adriamycin and methotrexate inhibit heterotopic new bone formation induced by demineralized bone matrix in rats to an equal extent, although their mode of action on the cellular level is entirely different, and that the inhibitory effect of a single treatment diminishes in the presence of a continuous inductive process. PMID- 2303953 TI - Vasoactive substances in subchondral bone of the dog knee. AB - The purpose of the present study was to investigate regulatory mechanisms for subchondral bone blood flow. A model including elevation of joint cavity pressure in the immature dog knee was applied. The role of prostaglandins in bone blood flow regulation was indirectly examined by indomethacin blockade. In six puppies, both venous tamponade of the joint cavity [50% of the mean arterial blood pressure (MAP)] and arterial tamponade (150% of MAP) resulted in a significant increase in the intraosseous pressure of the distal femoral epiphyses (p less than 0.05). During venous tamponade no changes were registered in pO2, pCO2, pH, potassium, and lactate in blood withdrawn from the distal femoral epiphyses. Arterial tamponade resulted in hypoxia, a decrease in pH, and increased lactate. Inhibition of the prostaglandin synthesis did not alter this response pattern. Thus, the present study suggests the presence of a regulatory mechanism for subchondral bone blood flow since venous tamponade did not significantly alter intraosseous gas tensions, pH, lactate, or potassium in spite of elevated venous outlet resistance. The study does not allow any conclusion as to the exact nature of the regulatory mechanism, but local metabolic regulation is likely to be involved as indicated by accumulation of vasoactive substances at higher tamponade levels. Prostaglandins are probably of minor importance in this regulation. PMID- 2303954 TI - Update on the use of distal radial bone density measurements in prediction of hip and Colles' fracture risk. AB - A controversy has developed around the question as to whether bone density values from the distal radius can be used to accurately predict risk of future fractures. To address this question, two separate studies were undertaken: (a) Bone density was measured in 460 healthy ambulatory women living in retirement centers in the state of North Carolina; 83% of these women were followed for up to 60 months for occurrence of minimal trauma hip and wrist fractures. Thirty-one minimal trauma fractures were reported in our study population, representing 8% of those followed. The fracture incidence density rate showed a close inverse relationship with incremental changes in bone density at the distal site. Twenty eight of the 31 fractures were reported in women with bone density values below the 325-mg/cm2 "at risk" value. (b) Bone density values of the distal radius and the lumbar spine from 360 women (aged 18-85 years) from the Chapel Hill area were used to analyze the error in predicting individual spinal density from the distal radial density. Although the overall correlation was high (r = 0.67) and the confidence intervals were narrow, the prediction intervals were quite wide. Thus, prediction of an individual value of spine density from the distal radius density would result in a value with a range too wide to be clinically useful. We conclude that single-photon absorptiometry appears to be a useful tool for screening normal populations of asymptomatic women for prediction of hip or Colles' fracture risk even though it has limited usefulness in prediction of spinal fracture risk or individual values for spinal density. PMID- 2303955 TI - Stimulation of adult chondrocyte metabolism by a thyroid-derived factor. AB - This paper reports the effects of adding partially purified bovine thyroid calcitonin, thyrocalcitonin, to adult bovine articular cartilage cells. Thyrocalcitonin stimulated chondrocyte proliferation fourfold under low serum (0.5%) culture conditions. In serum-free medium, thyrocalcitonin stimulated cell proliferation more than twofold. With high-density cultures in serum-free medium, chondrocyte glycosaminoglycan (GAG) synthesis was stimulated 60% by thyrocalcitonin. Cell-associated radioactivity was increased twofold. In contrast to thyrocalcitonin, addition of human and salmon calcitonin peptides as well as the thyroid hormones T3 and T4 had no effect on adult cartilage cell proliferation or GAG synthesis. The data reported here suggest the existence of a thyroid-derived factor, independent of calcitonin peptides or thyroid hormones, which stimulates adult articular chondrocyte metabolism. PMID- 2303956 TI - Effect of donor age on the growth in vitro of cells obtained from human trabecular bone. AB - The proliferation of human bone-derived cells (BDCs) was assessed in vitro, using [3H]thymidine incorporation and cell counting in a haemacytometer. The cells were cultured from human trabecular bone from 87 patients aged 2-88 years. The in vitro growth of these cells was unaffected by the chronological age of the donor. However, the cell number at confluence was shown to decrease with increasing donor age, this trend being most marked after 60 years of age. Other assays of the metabolic efficiency of the BDCs, namely, total protein, osteocalcin, and alkaline phosphatase synthesis, did not show any change with increasing donor age. These results suggest that while the ability of individual cells to divide and to perform specific synthetic activities is unimpaired with increasing age, other subtler changes may occur, leading to a decrease in the bone's osteogenic capacity. PMID- 2303957 TI - Internal remodeling of periosteal new bone during fracture healing. AB - A closed fracture model of the rat tibia was employed to study internal remodeling of periosteal new bone during fracture repair. Static histomorphometric parameters of osteoid surface (or perimeter) and eroded surface (resorption surface) were used as indicators of appositional bone formation and resorption of bone trabeculae, respectively. Intracortical remodeling at the fracture site was evaluated using quantitative tetracycline histology and microradiography. The extents of osteoid and eroded bone surfaces did not differ significantly in the periosteal woven new bone in the early phases of fracture healing. Later on, the periosteal new bone had significantly more osteoid surface than eroded surface (p less than 0.001). The number of osteoclasts also decreased significantly over time during fracture healing (p = 0.028). Cortical bone showed a continuous increase of porosity (p less than 0.01) between 1 and 6 weeks after fracture. These results suggest that there is a time-related change in the balance of periosteal bone formation and resorption during the progress of fracture repair. We hypothesize that this change was related to the restoration of bony continuity. Further studies are, however, needed to indicate the histomorphometric features of periosteal new bone in fracture nonunions. PMID- 2303958 TI - Dynamic electromyography. I. Numerical representation using principal component analysis. AB - A complete description of human gait requires consideration of linear and temporal gait parameters such as velocity, cadence, and stride length, as well as graphic waveforms such as limb rotations, forces, and moments at the joints and phasic activity of muscles. This results in a large number of interactive parameters, making interpretation of gait data extremely difficult. Statistical pattern recognition techniques can simplify this problem. For this approach to be successful, first it is necessary to reduce the number of interactive parameters to a manageable set. In this study, we present an application of principal component analysis as a means for representing graphic waveforms in a parsimonious manner. In particular, we concentrate on representing the phasic muscle activity recorded using surface electrodes from ten major muscles of the lower extremity of 35 normal subjects during level walking. A 32 point vector is created in which each point of the vector represents the normalized area under the curve of a portion of rectified and smoothed electromyographic signal, expressed as a function of gait cycle. Principal components are computed and the first few weighting coefficients are retained as features to represent the original EMG data. We show that the corresponding basis vectors span parts of the gait cycle where the most variability between individual subjects exists. We also show that the basis vectors can be used to represent the EMG data of subjects not originally used to generate the basis vectors. PMID- 2303959 TI - Dynamic electromyography. II. Normal patterns during gait. AB - Human gait is a complex phenomenon. Many descriptors are needed to completely describe gait in terms of the biomechanics involved. The descriptors, when expressed as a function of the gait cycle, are complex waveforms. For each of these variables, a single "normal" pattern with bands of deviation has generally been accepted as a reference in clinical/research use to explain the abnormalities in a patient's walking pattern. In fact, one observes many "normal" patterns, and a body of research has been devoted to explaining the differences between these patterns in terms of walking speed, age, cadence, sex, etc. It would be simpler in one sense to start with the fact that different people walk with different patterns, not one pattern with bands of deviation. Numerical representation of the waveforms simplifies the analysis and interpretation of waveform data and facilitates comparison between subjects or groups of subjects. When combined with pattern recognition techniques, it also is useful for identifying subpatterns within a group. In this article, the numerical representation of electromyographic data by Karhunen-Loeve expansion are combined with cluster analysis to obtain patterns of dynamic phasic activity of 10 muscles of the lower extremity. From the 35 normal subjects walking at self-selected speed, two to four patterns are developed for each of the muscles and the physiological significance of the patterns are discussed. PMID- 2303960 TI - Pulsing direct current-induced repair of articular cartilage in rabbit osteochondral defects. AB - Osteochondral defects in the distal femoral condyles of rabbits exposed to a pulsing direct current exhibits an enhanced quality of repair. The signal, with a peak value of 2 microA repeating at 100 Hz, imposed an electric field in the tissue of 20-60 mV/cm2. Maximum efficacy was seen with a shorter period of exposure (40 vs. 160 h) initiated 48 h after surgery for 4 h/day. Repair tissue originated primarily from metaplasia of subchondral elements although hyperplasia of pre-existing chondrocytes at the margins of the defect could be detected. Defects in treated joints contained Safranin O staining material that was histologically similar to a disorganized hyaline cartilage. Central areas of the defects in control animals contained Safranin O-negative material that generally extruded over the surface as a pannus. The edges of nontreated defects also had characteristics of cartilaginous healing, stressing the importance of using serial sectioning techniques in this model of cartilage repair. PMID- 2303961 TI - Effect of low frequency pulsing electromagnetic fields on skin ulcers of venous origin in humans: a double-blind study. AB - The effect of an electromagnetic field on the healing of skin ulcers of venous origin in humans has been investigated in a double-blind study. Forty-four patients have been admitted to the study; one-half were exposed to active stimulators (experimental group) and the remaining to dummy stimulators (control group). The stimulation was scheduled to last a maximum of 90 days. The success rate was significantly higher in the experimental group both at day 90 (p less than 0.02) and in the follow-up period (p less than 0.005). The data suggest that the effect of the electromagnetic field lasts even when the stimulation is over. No ulcers worsened in the experimental group, while four worsened in the control group. Twenty-five percent of the patients in the experimental group and 50% in the control group experienced recurrence of the ulcer. It is concluded that stimulation with an electromagnetic field is a useful adjunctive therapy in the management of these patients. PMID- 2303962 TI - Vascular changes in the chest wall after unilateral resection of the intercostal nerves in the growing rabbit. AB - In young, growing white New Zealand rabbits the third, fourth, and fifth intercostal nerves were resected anteriorly on the right side. Six months later the animals developed structural left convex scoliosis, with a Cobb angle ranging from 15 to 31 degrees. The vascular structure changes of the anterior chest wall were evaluated by measuring surface temperature and fluorescein intensity of the pectoral muscles, and the capillary density of the pectoral and intercostal muscle and periosteal parts of the ribs after angiography. In five normal control rabbits there was neither scoliotic deformity nor significant differences in the examined vascular variables between the right and left sides. In the animals undergoing resection, the temperature of the pectoral muscle on the side of the denervation--the right side--was significantly increased (p less than 0.05), but the difference was not correlated to the degree of scoliosis. The fluorescence index was significantly greater (p less than 0.05) on the right than on the left side, this difference being fairly strongly correlated to the degree of scoliosis. The capillary densities of the costal periosteum and the intercostal and the pectoral muscle were significantly greater (p less than 0.05) on the right than on the left side, and the difference was positively correlated to the degree of scoliosis. The volume density of the periosteum of the ribs was likewise significantly greater on the right. These results demonstrate that unilateral resection of the intercostal nerves significantly increases the vascularity of the structures on the denervated side of the thorax.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303963 TI - Blood flow evaluation of vascularized bone transfers in a canine model. AB - Blood flow in vascularized bone transfers was evaluated in a canine model. Cortical bone blood flow was determined in undisturbed control bone, vascularized heterotopic bone transfers, and nonvascularized cortical bone grafts by means of the radionuclide-labeled microsphere technique. Four animals were studied at 2 days, three at 1 week, eight at 2 weeks, four at 4 weeks, and three at 6 weeks postoperatively. In the 2-day animals, the vascularized bone transfers exhibited intermediate levels of blood flow (1.4 +/- 0.4 ml/100 g of bone/min) compared with undisturbed control bone (2.7 +/- 0.5 ml/100 g of bone/min) and conventional cortical bone grafts (0.0 +/- 0.0 ml/100 g of bone/min). At 1 week postoperatively, the differences in blood flow values of the vascularized transfers (1.7 +/- 0.7 ml/100 g of bone/min) and control bone (1.4 +/- 1.0 ml/100 g of bone/min) and of the nonvascularized grafts (0.2 +/- 0.1 ml/100 g of bone/min) and control bone (1.6 +/- 1.1 ml/100 g of bone/min) were no longer significant. At 2 weeks postoperatively, blood flow had increased in both graft groups. At 4 weeks postoperatively, the bone blood flow values in the vascularized transfers (4.8 +/- 1.4 ml/100 g of bone/min) were significantly greater than the bone blood flow in control specimens (1.6 +/- 0.5 ml/100 g of bone/min) and conventional cortical bone grafts (2.5 +/- 2.0 ml/100 g of bone/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303964 TI - Statistical significance and statistical power in hypothesis testing. AB - Experimental design requires estimation of the sample size required to produce a meaningful conclusion. Often, experimental results are performed with sample sizes which are inappropriate to adequately support the conclusions made. In this paper, two factors which are involved in sample size estimation are detailed- namely type I (alpha) and type II (beta) error. Type I error can be considered a "false positive" result while type II error can be considered a "false negative" result. Obviously, both types of error should be avoided. The choice of values for alpha and beta is based on an investigator's understanding of the experimental system, not on arbitrary statistical rules. Examples relating to the choice of alpha and beta are presented, along with a series of suggestions for use in experimental design. PMID- 2303965 TI - Chronic intestinal pseudo-obstruction: progress and problems. PMID- 2303966 TI - Postnatal maturation of the exocrine pancreas in mammals. PMID- 2303967 TI - Caustic ingestion and esophageal function. AB - The aim of the present study was to investigate esophageal motor function by means of krypton-81m esophageal transit scintigraphy and to compare the results with the functional and morphological data obtained by means of triple lumen manometry and endoscopy. In acute and subacute stages of the disease, all clinical, anatomical, and functional parameters were in good agreement, revealing significant impairment. In chronic stages, the severity of the dysphagia was not correlated to the importance of the residual stenosis. Conversely, 81mKr esophageal transit and manometric's findings were in good agreement with the clinical symptoms, during the entire follow-up period ranging between 3 months to 7 years. The 81mKr test is undoubtedly the easiest and probably the most physiological technique currently available for long-term functional evaluation of caustic esophagitis. PMID- 2303968 TI - IgA anti-gliadin antibodies in the monitoring of gluten challenge in celiac disease. AB - The aim of this study was to evaluate the reliability of serum IgA anti-gliadin antibodies (IgA-AGA) in the monitoring of gluten challenge and in the prediction of mucosal relapse in children with celiac disease (CD) in order to reduce the challenging procedure to a minimum. Serial evaluations of serum IgA-AGA titers and 1-h blood xylose levels were performed in 17 children with celiac disease during gluten challenge. Jejunal biopsy was generally done after two consecutive measurements of positive IgA-AGA. The morphological appearance of the mucosa and intraepithelial lymphocyte infiltration were also evaluated. A serum positive for IgA-AGA was observed in 16 of 17 patients between the 15th and 35th day of challenge. The challenge was concluded in all children after 20-45 days from the introduction of a gluten-containing diet after histological confirmation of CD. Plasma xylose test was less reliable in this respect. We conclude that IgA-AGA measurement by gluten challenge is likely to simplify and allow earlier diagnostic confirmation of celiac disease in children, without intestinal biopsy. PMID- 2303969 TI - Plasma vasoactive intestinal polypeptide in the newborn infant. AB - Vasoactive intestinal polypeptide (VIP) has been suggested as a possible contributor to the development of gastrointestinal problems. VIP is produced by nerve endings in the intestinal tract and appears to have marked effects on gut motility and its blood flow. Since necrotizing enterocolitis and feeding intolerance are common problems in the newborn, we examined the plasma VIP responses to feeding in healthy preterm and term newborn infants. Plasma VIP levels were measured in 20 full-term newborn infants (gestation of 39.4 +/- 0.9 weeks, mean +/- SD, and weight of 3,351 +/- 477 g) and 38 preterm infants (gestation of 27-35 weeks, weight of 920-2,440 g). In term infants, cord blood samples were obtained from the umbilical artery and vein and then before and after the feed. For preterm infants, blood samples were obtained prior to the introduction of oral feeds during the first week, and then before and after feeding once a week over the next 4 weeks. Feeding ranged from diluted premature formula to special care (24 calories per ounce) for the preterm, and breast milk or regular commercial formula for the term infants. Twenty-one healthy adults, age 25-42 years, were studied for comparison. In the term newborn infants, the plasma VIP levels in the umbilical venous blood were lower, although not statistically significant (p = 0.06), than the umbilical arterial blood (10.78 +/ 5.89 vs. 13.54 +/- 6.71 pmol/L), suggesting placental metabolism of VIP. After birth, there was a significant increase in plasma VIP levels (18.89 +/- 10.07 pmol/L, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303970 TI - Regulation of intestinal ontogeny by intraluminal nutrients. AB - Major events in gastrointestinal ontogeny occur in the infant rat in association with weaning, resulting in striking alterations in small intestinal structure and function. Although the dietary changes attendant to weaning are not essential for the initiation of these events, dietary nutrients have been shown to participate in the maturation of some intestinal parameters. In order to define more precisely the role of intraluminal nutrients in the regulation of small intestinal ontogeny, a longitudinal study was conducted using a unique animal model in which intraluminal nutrients were excluded from the intact maturing intestine in vivo throughout the entire weaning period without major compromise in nutritional status. The absence of intraluminal nutrients over the weaning period resulted in diminished lengthening and accretion of mucosal mass, suggesting a slower rate of intestinal growth. Lower mucosal DNA, protein, and mitotic indices in intestines of animals receiving no intraluminal nutrients suggested that the lack of intraluminal nutrients resulted in the blunting of the striking increases in cellular proliferation normally exhibited by the developing intestinal mucosa at this time. Maturation of intestinal lactase-phlorizin hydrolase and maltase-glucoamylase was not affected by the absence of intraluminal nutrients. Although the appearance of sucrase-isomaltase was not altered by the absence of intraluminal nutrients, activity levels rose to only 50% of control levels. These data suggest that during this period of rapid intestinal maturation, intestinal growth is more dependent upon intraluminal nutrients than are the characteristic enzymic alterations normally expressed during this period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303971 TI - Development of exocrine pancreas function in chronically cannulated pigs during 1 13 weeks of postnatal life. AB - The development of exocrine pancreas function was studied in Swedish Landrace pigs surgically fitted with a chronic pancreatic duct catheter and a duodenal re entrant cannula. The juice secretion and output of total protein and trypsin activity were followed before (basal secretion) and after feeding (postprandial secretion) during the first 1-13 weeks of life. The results showed that throughout the suckling period, up to 4-5 weeks of age, the basal pancreas function remained low and the secretory response to feeding, i.e., nursing sow milk, was also low. After weaning, the pancreatic juice secretion as well as the output of protein and trypsin activity markedly increased with respect to both basal and postprandial levels. Furthermore, the enzyme composition of the pancreatic juice changed qualitatively during this period. During the first 2 weeks of life, the intravenous administration of cholecystokinin (CCK) and secretin did not stimulate exocrine function, but a significant effect was achieved from 3-4 weeks of age. These results showed that there was both an increase in exocrine pancreas function and a qualitative change in the hydrolytic enzyme pattern during porcine postnatal ontogeny, apparently correlated with the changes in diet around weaning. An increase in the response of the pancreas to hormonal stimulation was also observed during the suckling period. PMID- 2303972 TI - Alanine stimulation of water and sodium absorption in a model of secretory diarrhea. AB - We investigated the effectiveness of L-alanine (Ala) addition to oral hydration solutions (OHSs) during secretory conditions induced by ileal instillation of 10 mM theophylline in anesthetized rats using a perfusion procedure, and monitoring water and sodium transport. Ala was added to two hypotonic OHSs in which the sodium:glucose ratio was 2:1, and compared with the OHS recommended by the World Health Organization (WHO), which has a sodium:glucose ratio of 0.81:1. Theophylline had the expected secretory effect on water and sodium absorption in the WHO-recommended OHS, and on sodium transport in a formula containing 60 mM sodium and 30 mM glucose. However, an OHS with 90 mM sodium and 45 mM glucose canceled the secretory effect of theophylline and yielded a greater rate of net water absorption than the WHO formula. Addition to this solution of either 15 or 30 mM Ala enhanced water and sodium absorption of both control and theophylline treated rats. In the hypotonic OHS with 60 mM sodium and 30 mM glucose, Ala had little effect on both sodium and water transport. Therefore, the data support the view that Ala added to solutions with 90 mM sodium, containing sufficient glucose to maintain a sodium:glucose ratio of not less than 2:1, is most effective at compensating fluid and sodium losses under secretory conditions. Ala presumably exerts its sodium-sparing effect because of its cotransport with sodium and the consequent water influx into the intestinal cells. PMID- 2303973 TI - Evidence for a pathogenic role of omega 6 polyunsaturated fatty acid in the cutaneous manifestations of biotin deficiency. AB - Abnormalities in fatty acid composition have been detected in biotin deficiency in humans and in the rat. However, the pathogenetic role of these abnormalities, if any, in the cutaneous manifestations of biotin deficiency is not clear. In a nutrient interaction experiment, we tested the hypothesis that an abnormality of omega 6 polyunsaturated fatty acid (PUFA) metabolism plays a pathogenetic role in the cutaneous manifestations. Five rats were fed an egg white diet that induces biotin deficiency; these rats developed the characteristic cutaneous abnormalities of biotin deficiency. Five additional rats were pair-fed the egg white diet and received Liposyn [77% linoleic acid (18:2 omega 6)]; these rats did not develop the cutaneous manifestations of biotin deficiency. The two groups had similar decreases in the rates of urinary excretion of biotin, the serum concentrations of biotin, the amounts of biotin in liver, and the hepatic activities of two biotin-dependent carboxylases; the two groups had similar increases in the rates of urinary excretion of 3-hydroxyisovaleric acid. These observations provide evidence that (a) some abnormality in omega 6 PUFA metabolism has a pathogenetic role in the cutaneous manifestations of biotin deficiency and (b) this pathogenetic role can not be explained as a difference in biotin nutritional status due to a biotin-sparing effect of Liposyn. PMID- 2303974 TI - Failure of liver transplantation in Wilson's disease with pulmonary arteriovenous shunting. AB - A 12-year-old boy with Wilson's disease developed exertional dyspnea, cyanosis, and finger clubbing 10 months after diagnosis. The hypoxemia was caused by arteriovenous shunting, demonstrated by radionuclide scanning and pulmonary arteriography. Orthotopic liver transplantation was performed after the development of severe hypoxemia. There was no apparent reversal of the intrapulmonary arteriovenous shunting and he died 10 days posttransplantation of multiple organ failure secondary to hypoxemia. Monitoring arterial oxygen saturation in children with cirrhosis is warranted since the presence of significant arteriovenous shunting may influence prognosis and decisions regarding liver transplantation. PMID- 2303975 TI - Gallbladder sludge and lithiasis in an infant born to a morphine user mother. AB - We report a 3-month-old boy with gallbladder sludge formation and lithiasis. The known associated factors causing cholelithiasis in infancy were not present. We postulate that maternal chronic use of morphine during pregnancy may result in biliary sludge formation in utero in the fetus with progression and manifestation of cholelithiasis at 3-months of age. PMID- 2303976 TI - Hepatotoxicity due to pemoline (Cylert): a report of two cases. AB - Pemoline (Cylert) is an agent used to treat attention deficit disorders and other behavioral syndromes. There have, however, been three published reports of mild hepatic dysfunction in five patients coincident with pemoline therapy. We report two further cases of probable pemoline hepatotoxicity. One case involved a mild aminotransferase elevation in a 6-year-old who was on pemoline for 5 months. The second case, in an 11-year-old, developed hepatic failure with marked prolongation in prothrombin time nonresponsive to parenteral vitamin K, deep jaundice, and submassive hepatic necrosis. This patient had a long history of pemoline usage. Pharmacokinetics are briefly discussed. A spectrum of hepatic disease due to pemoline is considered and the importance of obtaining aminotransferase values before, during initiation, and throughout treatment is stressed. PMID- 2303977 TI - Essential fatty acid deficiency mimicking porphyria cutanea tarda in a patient with chronic cholestasis. AB - Essential fatty acid deficiency was documented in a 3-year-old boy with chronic cholestasis secondary to paucity of intrahepatic bile ducts (Alagille's syndrome). Dietary management had consisted almost exclusively of a proprietary formula with over 80% of the fat as medium-chain triglycerides. The bullous lesions involved mostly sun-exposed areas and were diagnosed initially as being compatible with acquired porphyria cutanea tarda. Improvement followed correction of the fatty acid abnormalities with a polyunsaturated fat supplement administered orally. We postulate that the association of fatty acid deficiency and abnormal vitamin E status contributed to skin damage, possibly involving photosensitizing compounds poorly cleared by the markedly cholestatic liver. PMID- 2303978 TI - Intestinal lymphangiectasia without protein loss in a child with abdominal pain. AB - A 7-year-old white girl presented with recurrent abdominal pain because of gastroesophageal reflux. At endoscopy, we found intestinal lymphangiectasia in the duodenal biopsy. There were no physical signs, nor any laboratory evidence of enteric protein loss. PMID- 2303979 TI - Giardiasis with protein-losing enteropathy: diagnosis by fecal alpha 1 antitrypsin determination. AB - Giardia lamblia infection was documented by jejunal biopsy in a previously healthy 2-year-old boy with acute onset of hypoproteinemia due to protein-losing enteropathy. All symptoms and abnormal laboratory findings resolved with anti Giardia therapy. This is only the second case report of giardiasis with documented protein-losing enteropathy. Further application of the fecal alpha 1 antitrypsin assay may help to clarify the relationship between Giardia infection and protein-losing enteropathy and its role in development of malnutrition. PMID- 2303980 TI - Cyclosporin-responsive enteropathy and protracted diarrhea. AB - We describe a child born to unrelated parents who developed severe protracted secretory type diarrhea associated with subtotal villus atrophy and intestinal inflammation at the age of 19 months. No infectious, metabolic, or anatomical basis for this condition was identified and the child required total parenteral nutrition for a period of 18 months despite trials of special enteral formulas, steroids, and anti-inflammatory agents. This refractory "enteropathy" responded dramatically to the introduction of cyclosporin, with cessation of the secretory diarrhea, recovery from the enteropathy, and cessation of parenteral nutrition. The symptoms relapsed when cyclosporin was briefly discontinued and improved following reintroduction of this drug. This experience suggests a role for immune factors in the pathogenesis of the enteropathy in this case and that a trial of cyclosporin is worthy of consideration in similar cases. PMID- 2303981 TI - Bowel cocktail and severe persistent diarrhea. PMID- 2303982 TI - Gas chromatographic procedure for measuring total lipid in breast milk. PMID- 2303983 TI - Pitfalls in diagnosing galactosemia: false negative newborn screening following red blood cell transfusion. PMID- 2303984 TI - Liver biopsy diagnosis of Andersen's disease. PMID- 2303986 TI - Papers presented at the 20th annual meeting of the American Pediatric Surgical Association. Baltimore, Maryland, May 28-31, 1989. Part 2. PMID- 2303985 TI - The diagnosis of childhood giardiasis. PMID- 2303987 TI - Postoperative analgesia in children: a prospective study in intermittent intramuscular injection versus continuous intravenous infusion of morphine. AB - Few advancements in postoperative pain control in children have been made despite longstanding inadequacies in conventional intramuscular analgesic regimens. While overestimating narcotic complication rates, physicians often underestimate efficacious doses, nurses are reluctant to give injections, and many children in pain shy away from shots. This study prospectively focuses on the safety, efficacy, and complication rate of intermittent intramuscular (IM) versus continuous intravenous infusion (IV) of morphine sulfate (MS) in 46 nonventilated children following major chest, abdominal, or orthopedic surgical procedures. Twenty patients assigned to the IM group had a mean age of 6.17 years and a mean weight of 23.0 kg. Twenty-six patients assigned to the IV group had a mean age of 8.74 years and a mean weight of 27.4 kg. The mean IM MS dose was 12.3 micrograms/kg/h while the mean IV dose was 19.8 micrograms/kg/h (P less than .001). Postoperative pain was assessed with a linear analogue scale from 1 to 10 (1, "doesn't hurt"; 10, "worst hurt possible") for 3 days following operation. Using the analysis of covariance (ANACOVA), nurse, parent, and patient mean pain scores in the IV group were significantly lower than those of the IM group when controlled for age, MS dose, and complications (P less than .007). Nurse assessment of pain correlated well with the patient and parent assessments (Pearson correlation coefficients greater than 0.6). Not only did IV infusion give better pain relief than IM injections, but there were no major complications such as respiratory depression. Minor complications in this study (nausea, urinary retention, drowsiness, vomiting, hallucinations, lightheadedness, and prolonged ileus) were not significantly different between IM and IV groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303988 TI - Management of congenital microgastria. AB - Congenital microgastria is a rare anomaly. Only 22 cases have been reported in the literature. Its clinical manifestations depend on the stage at which the embryologic development of the stomach is arrested. The outcome of most patients with severe microgastria previously reported has either been death or extreme malnutrition. Since 1978, four patients with congenital microgastria have been managed at The Children's Hospital of Philadelphia. All patients had severe feeding intolerance and associated congenital malformations. Three patients were treated with a double lumen Roux-en-Y jejunal reservoir (Hunt-Lawrence pouch). This treatment improved the nutritional management of these patients. On follow up two patients are at the 50th percentile for height and weight, and one is at the 25th percentile. One patient with associated severe congenital heart disease was treated nonoperatively. Her nutritional management was difficult, and she ultimately died of congestive heart failure at 3 years of age. In patients with the most severe forms of microgastria, early operative treatment improves nutritional management and facilitates the achievement of normal growth and development. PMID- 2303989 TI - Malignant melanoma in children: its management and prognosis. AB - Malignant melanoma is rare in children, representing 1% to 3% of all pediatric malignancies. Thirty-three children with malignant melanoma were treated at St Jude Children's Research Hospital from 1967 to 1988. Their ages ranged from 1 day to 20 years (median, 12 years); 23 were boys and 10 were girls; and 5 of the 33 (15%) were black. Four of the 33 children had been treated for a previous malignancy. In 3, melanoma arose within a bathing trunk nevus. The extremity was the most common site (13), followed by the trunk (9), head and neck (7), and perineum (1). In 3 patients the primary site could not be determined. Upon initial presentation to St Jude Hospital, 17 patients had localized disease (stage I), 10 had regional node involvement (stage II), and the remaining 6 patients had disseminated disease (stage III). Using both Clark's level and Breslow's thickness as indicators, the incidence, initial stage, prognosis, and survival were compared. By Clark's level, 7 patients, (6 of whom were stage I) were level II or III, and 22 patients were level IV or V. Though 16 of 22 level IV and V patients were initially stage I, 10 patients eventually developed progressive disease. Similar observations were noted when using Breslow's thickness to evaluate the primary. In 5 of 27 evaluable patients, Breslow's depth of invasion was less than 1.5 mm. All 5 of these patients were diagnosed with stage I disease and have not shown progressive disease. PMID- 2303990 TI - Susceptibility of hepatic microcirculation to reperfusion injury: a comparison of adult and suckling rats. AB - Primary graft failure and vascular thromboses are frequent complications of liver transplantation, yet the mechanisms responsible remain unclear. Previous work from our laboratory has shown that hepatic reperfusion injury results in damage at the microvessel level. The present study was performed to determine whether an increased susceptibility of immature animals to microvascular injury during reperfusion might be a contributing factor in these complications. Suckling (35 to 50 g) or adult (250 to 400 g) rats were subjected to 30 or 60 minutes of hepatic ischemia to the left and median lobes followed by 90 minutes of reperfusion. Control animals were sham-operated, time-matched rats. At the end of reperfusion, fluorescein-labeled albumin was injected systemically to mark perfused sinusoids. Frozen sections of liver biopsies were viewed under fluorescence microscopy. The perfused sinusoid density was determined by point count analysis and expressed as the number of intersections of perfused sinusoids with 25 randomly oriented points superimposed on the sinusoid field. In sham operated rats, at both 30 and 60 minutes, there were no differences between sucklings and adults. After 30 minutes of ischemia and 90 minutes of reperfusion, adults showed a significantly decreased density of perfused sinusoids (4.5 +/- 0.1 intersections per field) when compared with suckling rats (6.0 +/- 0.3 intersections per field, P less than .001). However, in rats subjected to 60 minutes of ischemia followed by 90 minutes of reperfusion, the microvascular injury was more severe in suckling rats (2.7 +/- 0.2 intersections per field) than in adults (4.7 +/- 0.2 intersections per field, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2303991 TI - The role of leukocytes in mediating mucosal injury of intestinal ischemia/reperfusion. AB - The source of oxygen-free radicals in putative intestinal reperfusion injury is unknown. To define the role of the circulating leukocyte in this pathophysiology, we report a rat model of ex vivo intestinal perfusion that permits alteration of the intravascular perfusate. The validity of the model is proven by the degree of intestinal injury produced by reperfusion following occlusive ischemia. Severe damage was noted in the animals reperfused with normal blood; however, reperfusion with a white blood cell-free perfluorochemical significantly ameliorated this damage. The addition of leukocytes to the perfluorochemical negated the previously seen protection of the leukocyte-free perfusate. This study strongly suggests that the intravascular leukocyte is an important mediator of intestinal ischemia/reperfusion injury. PMID- 2303992 TI - Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains. AB - Since hydrogen peroxide (H2O2) can react with ferrous iron (FE++) to form the more toxic hydroxyl radical (OH) in vitro, and since H2O2 is generated brain xanthine oxidase (XO) during ischemia/reperfusion (I/R), we hypothesized that gerbils depleted of iron by dietary restriction or treated with iron chelators would be less susceptible to I/R injury. We found that gerbils fed a low iron diet for 8 weeks had decreased brain and serum iron levels, less neurologic deficits, and decreased brain edema after temporary unilateral carotid ligation (ischemia) and then reperfusion than gerbils fed a control standard iron diet. In addition, brains from gerbils treated with iron-free deferoxamine (an iron chelator), but not iron-loaded deferoxamine, had decreased (P less than .05) brain edema following ischemia and reperfusion. The results indicate that iron may contribute to cerebral ischemia/reperfusion damage. PMID- 2303993 TI - Factors predictive of mortality in pediatric extremity rhabdomyosarcoma. AB - In order to examine factors predictive of fatal outcome in children presenting with histologically confirmed extremity rhabdomyosarcoma, we performed a retrospective analysis of our institutional experience from 1970 to 1985. Thirty five patients were identified and staged according to international criteria (TNM). Variables evaluated for their predictive effect on fatal outcome included (1) tumor invasiveness, (2) tumor size, (3) anatomic location of the primary, (4) regional lymph node involvement, (5) distant metastases at presentation, (6) complete surgical resection, (7) use of amputation, and (8) alveolar histologic subtype. Significant predictors of mortality included (1) tumor invasiveness (P less than or equal to .0001), (2) regional node involvement (P less than or equal to .0002), (3) distant metastases at the time of presentation (P less than or equal to .001), (4) alveolar histology (P less than or equal to .001), (5) size of primary (P less than or equal to .007), and (6) completeness of surgical resection (P less than or equal to .05). In multivariate analysis, local tumor invasiveness was the most important predictor of fatal outcome with an associated relative risk of 18. We conclude that local tumor invasiveness is the most important determinant of clinical stage. PMID- 2303994 TI - Improvement in prognosis of neuroblastoma through mass population screening. AB - Since April 1981, the city of Sapporo, Japan, has conducted a mass screening program to measure urinary vanillylmandelic acid and homovanillylic acid using high-performance liquid chromatography. This program was expanded to the entire island of Hokkaido in October 1987. Mass screening proved beneficial, resulting in an increase in patients diagnosed with neuroblastoma under 1 year of age from 17% to 66%, an increase in stage I cases from 9% to 26%, an increase in stage III cases from 9% to 32%, and an increase in the tumor resectability rate from 15.1% to 58%. These improvements raised the 5-year survival rate for neuroblastoma from 23% to 66.7%. An additional study of these mass screening cases using Shimada's classification showed a wide range of histopathological distribution, and it demonstrated the usefulness of such a program in identifying the tumors most in need of early treatment. PMID- 2303995 TI - Ninety-five percent splenectomy for massive splenomegaly: a new surgical approach. AB - Subtotal splenectomy for children with Gaucher's disease has been a major contribution. When spleens of massive size are mobilized for partial resection, it may be technically difficult to remove more than 80% to 85% and still maintain hilar blood supply. The short gastric vessels are enlarged in patients who have marked splenomegaly and provide sufficient vascularity to support the 5% of remaining spleen that is desired in these patients. When the upper pole of the spleen is retained, as in the present case, the cut surface is relatively small and hemostasis is technically easier to achieve than when resection is performed closer to the center of the spleen. PMID- 2303996 TI - Elective splenopexy for wandering spleen. AB - The diagnosis of wandering spleen is usually made at the time of operation owing to symptoms caused by torsion of the spleen. Splenectomy has been performed in almost all of the reported cases. A 6-year-old girl presented with intermittent abdominal pain and a mobile abdominal mass. The diagnosis of wandering spleen was confirmed by computerized tomography. Elective splenopexy was performed by securing the spleen in an extraperitoneal pocket. PMID- 2303997 TI - Percutaneous transperineal pouch localization in low imperforate anus: a new approach. AB - Patients who have an imperforate anus with associated infralevator, or low rectal pouch, are candidates for a perineal anoplasty. However, in the absence of a perineal fistula, intraoperative localization and isolation of the rectal pouch can be difficult. We have developed a technique to facilitate isolation and dissection of the rectal pouch for perineal anoplasty in patients with a low imperforate anus who do not have a perineal fistula present. Pouch localization is carried out preoperatively by fluoroscopic percutaneous transperineal placement of a Fogarty embolectomy catheter through the center of the anal wink. We have used this technique successfully in four consecutive patients who had a low imperforate anus, in the absence of a perineal fistula, with the pouches 1.0 to 1.5 cm from the perineum. Results have been excellent, and the dissection of the rectal pouch was facilitated greatly by the presence of the inflated Fogarty balloon. PMID- 2303998 TI - Advantages of performing the sagittal anoplasty operation for imperforate anus at birth. AB - The development of the posterior sagittal anorectoplasty approach has been a major recent advance in the repair of imperforate anus. It has been found that sagittal anoplasty can easily and preferably be carried out in the newborn period without the need for colostomy or "tapering." It is suggested that the perineal sagittal approach be attempted first, with the infant positioned so that the abdominal part of the abdominoperineal approach can be used if necessary--this seldom may be required. Neonatal closure of urinary tract fistulas in boys is an added attractive feature of this approach. The importance of optical magnification (microsurgery) and excellent, intense lighting of the perineal area with a headlamp is stressed for this approach in the newborn, particularly for the management of high pouches and high fistulas. This operation at birth relieves alimentary tract obstruction at birth, eliminates urinary tract contamination (when it exists) at birth, establishes anorectal continuity and maximum potential for "normal" defecation reflexes at birth, and achieves all of this in one rather than three operations. PMID- 2303999 TI - Primary perineal rectovaginoanoplasty for supralevator imperforate anus in female neonates. AB - Sixteen girls (including 12 neonates), all of whom had supralevator anorectal anomalies usually with a high rectovaginal fistula, were treated by a primary rectovaginoanoplasty. None of these patients had any opening onto the perineum or into the vestibule. Through the perineum, with a dissection behind the vagina, the rectum was freed of any fistulous attachment and brought through the puborectalis sling to the perineum. Of the 12 patients now aged 2-years and over, 11 can control solid stools, and three soil with diarrhea only. The operation is easier than other available procedures, and the complications were minimal. PMID- 2304000 TI - Effects on CD4 binding of anti-peptide sera to the fourth and fifth conserved domains of HIV-1 gp120. AB - Antisera to peptides that represent regions within the fourth and fifth conserved domains of the human immunodeficiency virus type 1 (HIV-1) gp120 were tested for recognition of the gp120 glycoprotein and for the ability to interfere with gp120 binding to the CD4 receptor molecule. Antisera to both peptides contained equivalent antibody titers, showed equivalent reactions with denatured gp120 on Western blot, and had group-specific reactivity. Preincubation of gp120 with either anti-peptide sera prebound to a solid phase substantially blocked soluble CD4 binding to gp120. Similarly, preincubation of gp120 with CD4-positive cells substantially diminished recognition of gp120 by both anti-peptide antisera. These results provide serologic evidence that regions near or within the fourth and fifth conserved domains of gp120 are involved in CD4 binding. However, neither anti-peptide sera could block soluble gp120 from binding to CD4-positive cells nor inhibited HIV-1 envelope-mediated syncytium formation or virus infection. These results demonstrate that antisera to regions proximal to the CD4 binding site of gp120 may compete poorly with CD4 for gp120 binding. PMID- 2304001 TI - Risk factors for prevalent human immunodeficiency virus (HIV) infection in active duty Army men who initially report no identified risk: a case-control study. AB - A large proportion of human immunodeficiency virus antibody (HIV-Ab) positive male soldiers are considered to be at no identified risk (NIR) because they do not disclose histories of sexual activity with other men, intravenous drug use, blood transfusions, or sexual activity with persons at known high risk for HIV infection. A case-control study involving personal interviews with 26 NIR cases and 74 controls was conducted to determine if lifestyle information that might jeopardize a soldier's military career could be obtained from an Army population and to evaluate risk factors for prevalent HIV infection. Subjects consented to a voluntary, anonymous, and confidential interview containing information on demographic characteristics, medical history, drug use, and sexual behavior. Of 26 cases interviewed, 20 (76.9%) reported behaviors defined by the Centers for Disease Control (CDC) as risk factors for HIV infection, while 11 of 74 (14.9%) controls also reported such behaviors. This proportion of reclassified NIR cases was similar to that reported from the NIR case series study conducted by the CDC. Of the six (23.1%) cases who remained at NIR, all reported at least one of the following risks: a history of sexually transmitted diseases, sexual contact with prostitutes, or sexual activity with female partners which caused bleeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304002 TI - The effect of tuberculosis as a new AIDS definition criterion in epidemiological surveillance data from a south European area. AB - In this article, we evaluate the effect of the 1987 revised CDC AIDS definition on the AIDS epidemiological surveillance in Catalonia. From data collected in our population-based registry, we observed a 1.3- and a 1.6-fold increase in AIDS prevalence and incidence rates, respectively. In our setting, the new criteria appear to affect case ascertainment in male intravenous drug abusers, with extrapulmonary tuberculosis being the disease that accounts for the major increase in the identified cases. An additional effect of this case revision has been on the median survival time of AIDS patients, which will probably increase due to the use of the new definition criteria. PMID- 2304003 TI - HIV serosurveillance among prostitutes and patients from a sexually transmitted diseases clinic in Delhi, India. AB - Screening of 701 prostitutes in Delhi for HIV antibodies by a competitive ELISA test and supplementary Western blot test showed that only one of them was infected. Of the 4,572 samples from the patients attending a sexually transmitted disease clinic in Delhi, none showed evidence of HIV infection. In contrast to this low frequency of HIV infection in Delhi, a much higher frequency has been reported to the Indian Council of Medical Research from major metropolitan centers on the coast of India, namely, Bombay and Madras and their surrounding areas. It is possible that the infection is making inroads from these coastal areas to the interior of the country. PMID- 2304004 TI - Cholic acid derivatives against HIV replication. PMID- 2304006 TI - Podiatric manifestations of AIDS. AB - Dermatologic, vascular, neurologic, and musculoskeletal complications are common among persons with acquired immunodeficiency syndrome (AIDS). These manifestations frequently involve the lower extremities and may be the initial presenting symptoms of human immunodeficiency virus (HIV) infection. It is important that practitioners of podiatric medicine be aware of these syndromes to facilitate early diagnosis of AIDS and to provide the best possible care for immunodeficient patients. The author provides a review of the manifestations of AIDS frequently encountered in podiatric practice, along with guidelines for treatment. PMID- 2304005 TI - AIDS and HIV infection 1990 update. Introduction. PMID- 2304007 TI - HIV infection control for podiatric practitioners. AB - Although significant advances have been made in the treatment of acquired immunodeficiency syndrome (AIDS), neither a curative therapy nor a vaccine is available. Protecting practitioners, medical staff members, and patients from infection with human immunodeficiency virus (HIV) remains a particularly important issue. Fortunately, this virus is not readily transmitted in the health care setting. Adequate protection can be accomplished through the strict implementation of universal infection control policies in the treatment of all patients. Understanding these procedures, providing access to necessary equipment and supplies, and monitoring adherence to universal infection control measures will minimize the risk of exposure. PMID- 2304008 TI - Ethical dilemmas in HIV infection. AB - As the AIDS epidemic continues to claim lives, the issues of testing, confidentiality, and refusal to care for seropositive patients generate increasing debate and concern among health care workers, legislators, and the general public. Protecting the uninfected from exposure to HIV, providing adequate medical care and counseling to HIV-positive persons, and preventing discrimination are necessary and immediate goals. Adherence by practitioners to both the current legislation on AIDS and the ethical imperatives of the health professions will facilitate adequate access to health care for all persons with AIDS. It will also provide necessary guidelines for issues of confidentiality. PMID- 2304009 TI - Epidemiology and pathogenesis of HIV infection. Approaching the second decade. AB - Human immunodeficiency virus (HIV) is a retrovirus that can be transmitted through sexual activity, blood products, and perinatal exposure. The virus is composed of core, transmembrane, and envelope proteins. Cells of the immune system are the primary target of HIV, and destruction of the immune response is characteristic of end-stage disease. Although male homosexuals continue to represent the largest population of persons with acquired immunodeficiency syndrome (AIDS), transmission among intravenous drug users accounts for the rapidly growing incidence of pediatric and heterosexual AIDS patients. Control of the epidemic among intravenous drug users is the major challenge in the US today. PMID- 2304010 TI - AIDS education for the podiatric physician. Evaluating program impact. AB - An important component in the development of any educational program is the evaluation of its effectiveness. The program described in this article was designed in such a way that its impact on practitioners' knowledge, attitudes, and clinical practices regarding human immunodeficiency virus (HIV) could be evaluated. One hundred ten participants were asked to complete pre-conference and post-conference tests in order to measure improvement that resulted from program attendance. The author presents both a description of the conference and a summary of the evaluation results, along with suggestions for improving future educational programs. PMID- 2304011 TI - Foot care for the homeless. PMID- 2304012 TI - Crepitant cellulitis. PMID- 2304013 TI - Seroconversion, staging and survival. Natural history of HIV infection. AB - With the discovery of human immunodeficiency virus (HIV), researchers identified the etiologic agent for acquired immunodeficiency syndrome (AIDS). Although neither a cure nor a vaccine exists for this fatal disease, considerable information is now available on the progression from HIV infection through AIDS. Understanding the natural history of this progression can facilitate early detection and intervention. Although the epidemic continues to claim lives at an accelerating rate, the timely administration of prophylactic and therapeutic modalities can significantly prolong survival time for many patients. As more effective and less toxic treatments are developed, it will become increasingly crucial for practitioners to accurately diagnose and stage HIV-infected patients. PMID- 2304015 TI - Physician payment reform summary. PMID- 2304014 TI - Health promotion and podogeriatrics. A conceptual design for preventive services. AB - Because the majority of practicing podiatrists' received their professional training when less emphasis was placed on geriatrics, future continuing education activities should be expanded to upgrade a practitioners' understanding of elderly patients and the diagnosis and treatment of their foot problems, particularly among the frail elderly living at home or in nursing homes or other institutional settings. Efforts should also include special emphasis on the current publications in the profession on the subject of aging, including patient care, health care delivery, and other related topics. The podiatric medical profession stands ready, as it has always done, to care for the elderly with dignity and quality. The elderly should not be allowed to waste away because of their inability to help themselves. As we strive to meet these objectives and needs, there is no doubt that they will be met, as long as there is a national recognition of the needs and appropriate changes take place in the total health care delivery system to provide the mechanism for action. PMID- 2304016 TI - Friction blisters and sock fiber composition. A double-blind study. AB - A longitudinal double-blind study was conducted to determine the effect of sock fiber composition on the frequency and size of blistering events in long-distance runners. Thirty-five long-distance runners participated in this study. Two different socks were tested, which were identical in every aspect of construction except fiber composition. One test sock was composed of 100% acrylic fibers, and the other test sock was composed of 100% natural cotton fibers. The results showed that acrylic fiber socks were associated with fewer blistering events and smaller blisters (mm2), when compared directly to cotton fiber socks. PMID- 2304017 TI - Effect of desquamation of facial skin during surgery. AB - Aseptic control of organisms in the operating arena has long been a major goal of surgeons. The purpose of this study was to assess the facial skin flora of operating room personnel and its relationship to contamination adjacent to the surgical site. The authors found that, in spite of all attempts at aseptic control, operating room personnel have numerous organisms on the exposed facial areas, and the same organisms appear on the operating room table adjacent to the surgical site of about one in five patients. PMID- 2304018 TI - Veterans Administration Cooperative Studies Project No. 147: association of metallic taste with metal ceramic alloys. AB - We examined patients to find out whether they noticed the prevalence of metallic taste and set out to determine the association of metallic taste with demographic, medical, and dental factors. Data were collected as part of a Veterans Administration Cooperative Study investigating the suitability of alternative metal ceramic alloys as substitutes for alloys that contain gold. Crowns and fixed partial dentures were made from control and alternative alloys for accepted volunteer patients. A month after placement of the restorations and at regularly scheduled recall appointments, the patients were asked if they tasted a metallic flavor. Of the 2023 times the question was asked, 101 positive responses were given by 68 patients (46 reported metallic flavor once, and 22 reported it more than once). Results indicated that youth, sensitivity to heat and cold, bruxism, grinding, and an increasing number of restorative units were significantly related to metallic taste. For any given visit, about 5% of the patients reported tasting a metallic flavor regardless of the type of alloy that was used in the restoration. Metallic taste does not appear to be a problem with alternative alloys. PMID- 2304019 TI - Pulp response to a composite resin inserted in deep cavities with and without a surface seal. AB - The objective of the present investigation was to observe pulp response to a composite material (Occlusin) placed in deep cavities with and without a zinc oxide-eugenol covering. Deep cavities were prepared in 116 teeth of four young baboons and divided into four groups. In group 1, Occlusin material was placed directly into the cavity, without etching, to approximately half the depth, cured, and covered to the surface with zinc oxide-eugenol. In group 2, the cavities were etched, a bonding agent was applied, and Occlusin material was used and cured in two increments to fill the cavities up to the surface. In group 3, the composite resin was placed in two increments as in group 2, but without etching and bonding; and in group 4 (control), the cavities were filled up to the surface with zinc oxide-eugenol. Follow-up times were 5, 30, and 90 days. Light microscopy revealed that, although some differences were observed, a good pulp response was evident in all groups. PMID- 2304020 TI - A lining system for composite resin fillings. AB - Microleakage at the margins is a major problem with composite resin fillings. This study was performed to determine whether a liner that expands on contact with water could prevent leakage. A microfilled composite resin that has a high rate of contraction (taking place while curing) was used in class V cavities of extracted teeth. An experimental liner containing aluminosilicate crystals was painted on the dentin walls before insertion of the filling material. The specimens were thermocycled and sectioned. Class V fillings were also placed in the teeth of beagles. The teeth were extracted after 14 weeks. The depth to which the dye penetrated was measured microscopically. Results showed that the expanding liner almost completely prevented penetration of the dye in both in vitro and animal experiments. PMID- 2304021 TI - A comparison of new and conventional methods for quantification of tooth color. AB - Tooth color is caused by volume reflection, that is, passage of incident light through the tooth followed by backward emergence. This passage is concurrent with sideward displacement of photons that, in effect, influences the result of usual instrumental methods of determining tooth color. This problem is overcome by the use of large-field illumination and small-field observation. A fiber-optics colorimeter based on this principle is described. The color observed through two holes in a double box was visually matched by subtractive adjustment of the illuminating color in one box, whereas the other box showed the central part of the tooth diffusely illuminated by illuminant C light. This colorimeter was tested on wet, extracted human incisors in the tooth arch of a phantom-head. Results were compared with a visual standard-strip method described previously and with a conventional spectrophotometer. It was concluded that the fiber-optics colorimeter is a promising instrument, although technical improvement is necessary. PMID- 2304022 TI - The loss of occlusion and its effect on mandibular immediate side shift. AB - Mandibular immediate side shift is a lateral movement of the condyles at the commencement of mandibular laterotrusion. Amount of mandibular immediate side shift has been found to vary among patients and bilaterally within patients. Factors responsible for variance in mandibular immediate side shift have been suggested but not thoroughly investigated. Because of the clinical importance of the mandibular immediate side shift, this study attempted to demonstrate that one suggested factor--the loss of occlusion--would result in increased mandibular immediate side shift. Subjects were placed into one of four groups that had a varied amount of occlusion. Surprisingly, among groups no differences were detected in the amount of mandibular immediate side shift. Therefore loss of occlusion as a suspected cause of an increase in the amount of mandibular immediate side shift was not substantiated. Restorative therapy recommended on the basis of such an assumption will most likely prove inaccurate. PMID- 2304023 TI - Fabrication of a custom recessed tracheostoma valve retainer for the total laryngectomy patient. AB - Total laryngectomy patients who depend on a prosthesis for the production of alaryngeal speech often have irregular peristomal anatomy. The standard tracheostoma (speech) valve retainer cannot be intimately adapted to uneven and highly mobile tissue. Fabrication of a custom speech valve retainer is indicated under such circumstances but may be complicated by restricted access to the surgically created stoma. This article describes the clinical and laboratory techniques for the fabrication of a custom tracheostoma valve retainer that displaces the peristomal soft tissues and musculature. This technique permits access for placement of the speech valve and valve retainer in close proximity to the speech button prosthesis. Enclosure of the custom retainer in the recess underlying the peristomal musculature also provides a plug that enhances retention and increases patient confidence during alaryngeal speech. The coordinated efforts of the speech specialist and the prosthodontist in the fabrication of this prosthesis enhances the quality of life for the total laryngectomy patient. PMID- 2304024 TI - Palatopharyngeal activity in cleft palate subjects. AB - A literature review of the nature of the musculature of the cleft palate and the pharynx is provided and a rationale presented for determining the anatomic level at which muscle activity occurs. Nasal endoscopy with a rigid telescope and the placement of miniaturized pressure transducers against the pharyngeal walls were the techniques used to investigate palatopharyngeal defects in cleft palate subjects. Ten basic patterns of palatopharyngeal movement are described and the likely interplay of the various muscles in producing these complex movements is discussed. Closure patterns of the palatopharyngeal isthmus varied according to whether the subjects were speaking, sucking, or swallowing. It was concluded that the presence of an obturator in the pharynx affects the pattern of activity and that the obturator should be developed to speech function rather than to swallowing. PMID- 2304025 TI - Patterns of mandibular movements in subjects with craniomandibular disorders. AB - Mandibular movements were evaluated for border and functional movements in 24 adult normal subjects and 26 adult patients with muscle pain associated with a craniomandibular disorder. The mandibular incisor position was tracked with an electromagnetic system in three planes by use of either a Myotronic Kinesiograph or a Siemens Sirognathograph instrument while the subject sat in an upright position. In the normal subjects, the maximum movements of the mandible in lateral, protrusive, and vertical directions were compared with the envelope of movement during speech and mastication. The range of the rest position was 1 to 5 mm in relation to the intercuspal position; the range of maximum excursion during speech was 30% to 36% of maximum opening; the vertical extent of excursion during mastication was 18% to 90% of the maximum vertical opening dependent on the bolus. Protrusive movements were straight forward, dividing the angle evenly between left and right laterotrusion. Laterotrusive movements were of equal length and similar to the length of protrusion. Twenty-six patients with muscle pain, in many instances, demonstrated asymmetry in the length of laterotrusive movements. Different pathways for moving the mandible away from the intercuspal position and returning to this position could be seen during laterotrusion. Unequal laterotrusive excursions and asymmetrical, nonparallel movement patterns for mandibular protrusion and retrusion were often observed. In contrast, the extent of the speech envelope and the envelope of mastication were similar to that of the controls. PMID- 2304026 TI - Comparison of mandibular bone in normal and osteoporotic women. AB - This study compared dental findings in normal and osteoporotic women and evaluated the variables that best separated the two groups. The osteoporotic group had less mandibular bone mass and density and a thinner cortex at the gonion than the normal group. The osteoporotic group also had a greater percentage of subjects who were edentulous. In subjects who had natural teeth, there was greater tooth loss. No differences in periodontal measurements were found between osteoporotic and normal groups. Mandibular bone mass and the number of teeth were statistically most effective for separating the populations. However, considerable overlap was found between the osteoporotic and normal groups in all variables. PMID- 2304027 TI - Effect of disinfectant solutions on the wettability of elastomeric impression materials. AB - The wettability of impression material affects the number or volume of air bubbles generated during the pouring of gypsum casts. This study was done to determine the effect of various commercial disinfectant solutions on the wettability of elastomeric impression materials. The technique of measuring advancing contact angles of aqueous solutions of calcium sulfate was used to determine changes in the wettability of four types of impression material before and after immersion in one of five disinfectants. All disinfectant solutions that were tested increased the wettability of polysulfide. Chlorine dioxide produced the greatest increase in the wettability of polysulfide by decreasing the contact angle on polysulfide at least 48 degrees. All disinfectants decreased the wettability of hydrophilic addition silicone by increasing the contact angle up to approximately 30 degrees. The differences were significant as determined by paired Student t-tests. Addition silicone was the material most resistant to change in contact angle. Chlorine dioxide had the greatest beneficial effect on wettability. PMID- 2304028 TI - A procedure to sterilize dental burs with dry heat. PMID- 2304029 TI - Freeze-fracture study of the bloodstream form of Trypanosoma brucei gambiense. AB - The ultrastructure of Trypanosoma brucei gambiense was investigated by the freeze fracture method. Three different regions of the continuous plasma membrane; cell body proper, flagellar pocket, and flagellum were compared in density and distribution of the intramembranous particles (IMP's). The IMP-density was highest in the flagellar pocket membrane and lowest in flagellum. Intra membranous particles of the cell body membrane were distributed uniformly on both the protoplasmic (P) and exoplasmic (E) faces. On the P face of the flagellar membrane, a single row of IMP-clusters was seen along the juncture of the flagellum to the cell body. Since the spacing of the IMP-clusters was almost equal to the spacing of the paired rivet structures observed in thin section, these clusters likely are related to the junction of flagellum and cell body. At the neck of the flagellar pocket, several linear arrays of IMP's were found on the P face of the flagellar membrane, while on the E face rows of depressions were seen. At the flagellar base, the clusters of IMP's were only seen on the P face. On the flagellar pocket membrane, particle-rich depressions and linear particle arrays were also found on the P face, while on the E face such special particle arrangements were not recognized. These particle-rich depressions may correspond to the sites of pinocytosis of the bloodstream forms which have been demonstrated in thin sections. PMID- 2304030 TI - Continuous growth and differentiation of Trypanosoma (Megatrypanum) freitasi Rego, Magalhaes & Siqueira, 1957, in vitro. AB - Trypanosoma (Megatrypanum) freitasi, a parasite of didelphid opossum, was known to be very difficult to cultivate in conventional media. Co-cultivation with L929 cell line in Baltz's medium at 27.5 degrees C resulted in luxuriant growth of the trypanosome with the production of epimastigote colonies that adhered to the surface of culture flasks or tubes, and transformation into metacyclics. Further transformation was stimulated by raising the incubation temperature. At 37 degrees C the population was of the bloodstream type and resistant to lysis by complement. PMID- 2304031 TI - Developmental stages of Trypanosoma (Megatrypanum) freitasi Rego, Magalhaes & Siqueira, 1957 in the opossum Didelphis marsupialis (Marsupialia, Didelphidae). AB - Trypanosoma (Megatrypanum) freitasi, a parasite of marsupials of the genus Didelphis, has been found to undergo in the lumen of the scent (anal) glands of its vertebrate host, a cycle such as usually occurs in the intestinal tract of the insect vectors of trypanosomatids and similar to what has been reported for Trypanosoma (Schizotrypanum) cruzi. The invertebrate host of Trypanosoma freitasi is still unknown. Developmental stages of the trypanosome in its mammalian host, especially the dividing epimastigotes, multinucleate plasmodial forms and rosettes found in the lumen of the scent glands of a naturally infected Didelphis marsupialis are described and illustrated. PMID- 2304032 TI - Ortholinea alata n. sp. (Myxosporea: Ortholineidae) in the northern butterfly fish Chaetodon rainfordi. AB - Ortholinea alata n. sp. is described from the northern butterfly fish, Chaetodon rainfordi collected at Heron Island, Great Barrier Reef, Australia. Spherical, disporous trophozoites (10-15 micrometers) and spores were observed in the lumina of kidney tubules and collecting ducts. Spores are broadly triangular with two short, broad processes that extend dorsoventrad from the posterior end of each of the two spore valves. Valves are bisected by a suture in the plane of the polar capsules. Spores are 12.6 micrometers (length) x 9.6 micrometers (width) x 9.9 micrometers (length), and at the anterior end contain two spherical, divergent polar capsules measuring 4.6 (4.1-5.1) micrometers. Sporogenesis is similar to that of renal Sphaerospora spp.; the intraluminal trophozoites of O. alata n. sp. correspond to pseudoplasmodia described for Sphaerospora spp. and no large, multinucleated plasmodia are formed. No significant histopathological changes were observed in the kidneys of infected fish. PMID- 2304033 TI - Coping with caregiving. Stress management for caregivers of the elderly. PMID- 2304034 TI - Reducing AIDS anxiety on the unit with preventive infection control. PMID- 2304035 TI - Effect of monoclonal antisperm antibodies on the penetration rates of human spermatozoa in zona-pellucida-free hamster oocytes. AB - The penetration rate of human spermatozoa in zona pellucida-free hamster oocytes was reduced by four monoclonal antisperm antibodies (A-24, B-20, III3 and VII-5) of six tested. The other two (VI-1 and VI-16) left the penetration rates virtually unchanged. The extent of the penetration rate reduction depended on the concentrations of antibodies A-24, B-20, III-3 and VII-5; if undiluted, they produced a significant reduction in the penetration rates; the largest average reduction was almost 50% with undiluted antibody A-24. Decreasing concentrations of the monoclonal antisperm antibodies resulted in significantly smaller reductions in the sperm penetration rates. The reason for the reduced penetration rates observed might have been a blockage of receptors on the sperm surface by the antibodies. That can inhibit enzyme reactions of the spermatozoa or interfere with the interaction between oocyte and spermatozoon membranes. Only antibody III 3 caused agglutination of human spermatozoa in the micro sperm agglutination and immobilization tests. Therefore, the agglutination or immobilization of spermatozoa might not be responsible for the reduced penetration rates after the addition of monoclonal antibodies, in contrast to findings with polyclonal antibodies. PMID- 2304036 TI - Comparison of TestPack and Ovustick for predicting ovulation. AB - A study was designed to compare two methods of predicting the time of ovulation by detection of the urinary luteinizing hormone (LH) surge with two immunoassay kits designed for home use. A newly developed kit, TestPack, was compared with an existing kit, Ovustick. A group of 20 women with regular cycles were studied for one menstrual cycle. Ovulation was established with a serum LH surge and disappearance of the dominant follicle using transvaginal sonography followed by a rise in the serum progesterone level. In the 20 subjects, presumptive evidence of ovulation was obtained by determining the LH surge and the subsequent progesterone peak. In 18 of the 20, disappearance of the dominant follicle was also documented. Ovulation was predicted in 17 of the 20 subjects by both TestPack and Ovustick. Both tests were effective in predicting the day of ovulation, but TestPack provided a more easily defined end point and required less time and effort to perform. PMID- 2304037 TI - Ultrarapid freezing and thawing of hamster oocytes. Morphologic parameters, trypan blue staining and sperm penetration assay for evaluating survival. AB - Nine hundred sixteen hamster oocytes were cryopreserved with the ultrarapid freezing method using five different cryoprotective solutions: 3 mol/L dimethylsulphoxide (DMSO) plus 0.25 mol/L sucrose, 3 mol/L DMSO, 3 mol/L propanediol plus 0.25 mol/L sucrose, 3 mol/L propanediol and 10% glycerol. One hundred eighty fresh oocytes served as controls. The viability of the oocytes was evaluated using morphologic parameters, Trypan blue staining and the sperm penetration assay. The viability rates based on morphologic parameters and Trypan blue staining were 82.3%, 65.0%, 51.4%, 33.0% and 0%, respectively, as compared to 100% in the controls. The sperm penetration rates were 27.0%, 0%, 9.8%, 0% and 0%, respectively, as compared to 94-98% in the controls. Our results indicate that among the various cryoprotective solutions used for ultrarapid freezing, 3 mol/L DMSO plus 0.25 mol/L sucrose gave the best results, with a viability rate of 82.3% and a sperm penetration rate of 27%. PMID- 2304038 TI - Fetal heart rate cyclicity during preterm labor. AB - The cyclic variation in fetal heart rate (FHR) patterns in preterm fetuses throughout labor was studied with a retrospective analysis of 49 FHR tracings. All fetuses were born preterm in good condition, and 92% exhibited the ability to change FHR cycles. A cycle was defined as an FHR pattern with consistent long term variability in terms of amplitude range. The FHR cycles were significantly shorter in the second stage of labor as compared to the latent and active phases. Cycles of markedly diminished variability (less than or equal to 2.5 beats per minute) were observed in 16% of the fetuses during the latent phase and had a mean duration of 42 minutes, in 21% of the fetuses during the active phase with a mean duration of 68.3 minutes and in 8% of the fetuses during the second stage with a mean duration of 28.5 minutes. Knowledge of the normal length and frequency of FHR cycles is imperative for the correct interpretation of intrapartum FHR patterns in preterm fetuses. PMID- 2304039 TI - Maternal and fetal effects of heroin addiction during pregnancy. AB - Heroin addiction during pregnancy has been reported to be associated with adverse maternal and perinatal effects. In a study of a large obstetric service in Dallas, pregnancy outcome and health status of infants born to 24 heroin addicts were compared to those in a group of 100 unexposed women and their infants. Women who used heroin during pregnancy tended to use other substances (tobacco, alcohol, cocaine) more often than did controls. The frequency of preterm birth was increased significantly in women who abused heroin during pregnancy. Sexually transmitted diseases were not increased in frequency in pregnant heroin addicts as compared to women who did not use heroin during pregnancy. Heroin addicts had infants who were significantly shorter and lighter in weight than did controls. No significant differences in head circumference or frequency of congenital anomalies were observed. PMID- 2304040 TI - Twinning in southern Israel. Seasonal variation and effects of ethnicity, maternal age and parity. AB - Seasonality of births in southern Israel was examined in two populations, Jews and Bedouins, with distinctly different life-styles. The study included 1,444 twin births that occurred between the years 1970 and 1986. The peak month for the birth of monozygotic twins was September in both populations, while the maximum number of deliveries occurred in January for the Bedouins and August for the Jews. Of Jewish dizygotic twin births, higher rates were found from July to December. In addition, the peak months of singleton births in women aged 35 years and older and in women of high parity did not coincide with the peak months of multiple births. Maternal age and parity have been shown to greatly influence twin birth rates. The autumnal peak we found, which was independent of ethnic origin and its associated cultural and sociologic differences, was also independent of maternal age and parity and was consistent with findings in other populations in the northern hemisphere. That finding suggests that a seasonal factor, as yet undefined, affects the rates of multiple births. PMID- 2304041 TI - Transvaginal-peritoneal migration of Trichomonas vaginalis as a cause of ascites. A report of two cases. AB - Genital tract colonization with Trichomonas vaginalis usually results in vaginitis without systemic manifestations. There are only four recorded cases of Trichomonas recovered from pelvic organs or peritoneal fluid. This report describes two additional women in whom motile flagellate organisms were recovered from abdominopelvic ascites. We hypothesize that an ascending trichomonal infection may have played an etiologic role in the development of their acute disease. PMID- 2304042 TI - Prenatal diagnosis of and midtrimester pathology with karyotype 46,XY,del(4)(q22q26). A case report. AB - A prenatal diagnosis of an interstitial deletion with chromosome 4,46,XY,del(4)(q22q26) was obtained on amniotic fluid cells drawn at 19 weeks' gestation from a 35-year-old gravida. Counseling on the basis of unusual or tenuous data is always difficult, but comparisons with similar deletions in 4q suggested a substantial risk of anomalies. A comparison of the postabortal autopsy findings with those from other reported cases of interstitial deletions of chromosome 4q suggested different pathology with this area of deletion than previously reported for other areas of 4q. PMID- 2304043 TI - Ovarian pregnancy diagnosed after a failed midtrimester therapeutic abortion. A case report. AB - Ovarian pregnancy is a rare phenomenon. Its presentation often is difficult to distinguish from that of tubal ectopic pregnancy and hemorrhagic ovarian cyst. A patient had an ovarian pregnancy diagnosed following failed midtrimester therapeutic abortion in a suspected bicornuate uterus. Despite vaginal prostaglandin suppositories and intraamniotic instillation of urea and prostaglandin, neither the abortion process nor rupture of the ovarian pregnancy ensued. This is the first reported case of this most unusual presentation of ovarian pregnancy. PMID- 2304044 TI - Childhood anogenital lichen sclerosus. A case report. AB - Childhood lichen sclerosus is a rare disorder. A 4-year-old girl with chronic vulvar pruritus who was initially suspected to be the victim of child abuse was treated. Vulvar biopsy was performed, confirming the diagnosis of lichen sclerosus. The child was treated with 2% progesterone cream, with complete resolution of her pruritic symptoms and signs of traumatic injury to the vulvar skin. The basic condition, lichen sclerosus, has persisted. PMID- 2304045 TI - Torsion of the gravid uterus. A report of two cases. AB - Two cases of 180 degree torsion of the term uterus occurred. Both patients recovered uneventfully. PMID- 2304046 TI - Chlamydia trachomatis and inflammatory bowel disease--a coincidence? AB - Serological tests of 35 patients suffering from inflammatory bowel disease were compared to those of 35 healthy controls. The tests were performed using the indirect immunoperoxidase assay. Ninety-three per cent of 15 patients with Crohn's disease had IgG antibodies against Chlamydia, compared to 26% in the control group. In the 20 patients with ulcerative colitis, 45% had IgG antibodies against Chlamydia, compared to 10% in the control group. High serum titres of IgG antibodies were found in most of the patients with inflammatory bowel disease, mainly with Crohn's disease, while weak reactions appeared in most of the controls in which antibodies were detected. These results suggest a high incidence of Chlamydia infection in the studied patients with inflammatory bowel disease, especially in those with Crohn's disease. The possible association between Chlamydia trachomatis and inflammatory bowel disease is discussed. PMID- 2304047 TI - Domiciliary nebulized pentamidine for secondary prophylaxis against Pneumocystis carinii pneumonia. AB - The viability of a programme for delivering aerosolized pentamidine within the patient's home setting for the secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) has been explored with seven homosexual AIDS patients, the major objectives being the assessment of the safety and acceptability of the treatment and the discovery of the most suitable care setting (home, ward, outpatient clinic) for the administration of therapy. It is concluded that a domiciliary prophylaxis programme is a viable alternative. PMID- 2304048 TI - The future of health care for the elderly. PMID- 2304049 TI - An investigation into factors that may influence tonsil morphology. AB - To investigate whether tonsillar size was related to human morphology, age or duration of disease, 100 consecutive patients undergoing tonsillectomy for recurrent tonsillitis were investigated. The lengths, widths and volumes of each resected tonsil were measured and compared with patient characteristics ascertained on the day before surgery. The volume of tonsillar tissue was directly related to height (p = 0.46, P less than 0.001) and weight (p = 0.45, P less than 0.001) and age, but at any age (or body size) there was a wide range of tonsil size. A weak inverse relationship was found with the duration of recurrent tonsillitis. Tonsil size is of no relevance in the assessment of recurrent tonsillitis or adenoid hypertrophy. PMID- 2304050 TI - Pharmacocavernometry in the assessment of erectile impotence. AB - Thirty-three impotent men underwent pharmacocavernometry and cavernography. Ten patients had a good clinical response to 60 mg papaverine, nine had a moderate clinical response and in 14, the response was judged to be a poor one. Twelve patients had evidence of abnormal venous leakage from the corpora. Subsequent investigation with isotope phallography showed six patients to have arterial insufficiency and in three of these patients this was amenable to reconstructive vascular surgery. We conclude that pharmacocavernometry provides a useful, cheap and reliable method for the investigation of impotent men which may be performed on an outpatient basis. PMID- 2304051 TI - Current approaches to the orthodontic management of cleft lip and palate. PMID- 2304052 TI - Academic occupational medicine at the crossroads. PMID- 2304053 TI - Chondrosarcoma--local recurrence and systemic embolization. PMID- 2304054 TI - Late secondary syphilis altered by systemic corticosteroids in a human immunodeficiency virus antibody positive man. PMID- 2304055 TI - Spinal cord compression associated with pseudohypoparathyroidism. PMID- 2304056 TI - Primary intraocular lymphoma with lymphomatous meningitis. PMID- 2304057 TI - Metastatic carcinoid tumour in association with small bowel ischaemia and infarction. PMID- 2304058 TI - Colonic perforation with a phosphate enema. PMID- 2304059 TI - Leber's optic neuropathy and mitral valve prolapse. PMID- 2304060 TI - Early postoperative feeding--a continuing controversy in pyloric stenosis. PMID- 2304061 TI - Hyperparathyroidism in a patient with myotonic dystrophy. PMID- 2304062 TI - Review of medical audit. PMID- 2304063 TI - Spontaneous rupture of the oesophagus(Boerhaave's syndrome) PMID- 2304064 TI - Pathogenic potential of Eubacterium yurii subspecies. AB - Several mechanisms that could contribute to the periodontopathogenic potential of Eubacterium yurii were investigated. All 18 strains examined produced RNAase and the metabolites H2S, indole and butyrate. Some strains produced phosphatase and DNAase. Methanol extracts of whole cells of E. yurii subspp. yurii and margaretiae stimulated bone resorption in vitro comparable to that produced by recognised periodontal pathogens. These results suggest that further studies should be performed to elucidate the role of E. yurii in periodontal disease. PMID- 2304065 TI - Survival of Pseudomonas pseudomallei in human phagocytes. AB - Pseudomonas pseudomallei causes the disease melioidosis, with protean manifestations, protracted clinical course and unpredictable response to antimicrobial treatment. Intracellular location of the organism is suspected to be the cause of these properties. This study was undertaken to examine the intracellular growth of this bacterium. Intracellular growth and survival was assessed at different time intervals, by Gram's stain and electronmicroscopic examination. During the first 5 h, the numbers of P. pseudomallei within phagocytes did not change significantly. By 18-21 h, gram-stained preparations revealed that P. pseudomallei cells completely filled the phagocytes and electronmicroscopy showed evidence of binary fission. During that time the number of cfu of P. pseudomallei growing simultaneously in vitro increased by log10 2-3. The phagocytes remained viable throughout the observation period and retained their capacity to produce an oxidative burst for the first hour of incubation. The ability of P. pseudomallei to survive and multiply in phagocytes shows that it is a facultative intracellular bacterium. This finding is relevant to the selection of antimicrobial regimens, and the management of the disease. PMID- 2304066 TI - Chromosomal aberrations in germ cells of male mice immunised with attenuated viral vaccines (human). AB - The cytogenetic effects of two attenuated viral vaccines (yellow fever vaccine and oral poliomyelitis vaccine) were assessed by means of the analysis of meiotic spermatocyte chromosomes in mice. In a dose of 0.5 ml, but not 0.1 ml, both vaccines induced a significant percentage of chromosomal aberrations after 7, 14 and 30 days. Euploidy was the major abnormality produced by yellow fever vaccine. The various abnormalities produced by oral polio vaccine were significant when pooled, but not when analysed individually. More abnormalities were produced by yellow fever vaccine than by oral polio vaccine. PMID- 2304067 TI - A comparison of specificity and biological activity of polyclonal and monoclonal antibodies raised against Salmonella minnesota R595 lipopolysaccharide. AB - Murine monoclonal antibodies (MAbs) and immune rabbit serum were raised against the rough mutant of Salmonella minnesota strain R595. These antibodies were tested for their ability to inhibit LPS-induced B-cell mitogenicity and neutralise LPS toxicity in chick embryos. Immune rabbit serum inhibited both mitogenicity and LPS lethality. None of the MAbs or a cocktail of antibodies were able to neutralise LPS lethality in chick embryos. However, they were able to inhibit mitogenicity by varying degrees. PMID- 2304069 TI - Inversion of extracellular current and axial voltage profile in Chara and Nitella. AB - Reducing the pH of the bathing solution from 8.2 to pH 6 can induce an inversion of the extracellular current pattern that develops at the surface of Chara corallina internodal cells. A similar result can be obtained on some cells by changing the medium to a pH value of 10. In noninverting Chara cells the currents were strongly reduced when the pH value of the medium was changed between 3 and 11. Simultaneous measurements of the Chara transmembrane potential in the acid and alkaline regions revealed that a light-induced electrical potential gradient of approximately 24 mV was present in the axial (or longitudinal) direction. Correlated to the external current pattern inversion was an inversion of this internal longitudinal voltage gradient. Reillumination of Nitella cells, after a period of darkness, often resulted in a complete inversion of the extracellular current pattern. These results are discussed in terms of spatial and temporal control of membrane transport processes, and in particular the control of current loops that pass through these cells. PMID- 2304068 TI - Sulfhydryl-reactive heavy metals increase cell membrane K+ and Ca2+ transport in renal proximal tubule. AB - The cellular mechanisms by which nephrotoxic heavy metals injure the proximal tubule are incompletely defined. We used extracellular electrodes to measure the early effects of heavy metals and other sulfhydryl reagents on net K+ and Ca2+ transport and respiration (QO2) of proximal tubule suspensions. Hg2+, Cu2+, and Au3+ (10(-4)M) each caused a rapid net K+ efflux and a delayed inhibition of QO2. The Hg2(+)-induced net K+ release represented passive K+ transport and was not inhibited by barium, tetraethylammonium, or furosemide. Both Hg2+ and Ag+ promoted a net Ca2+ uptake that was nearly coincident with the onset of the net K+ efflux. A delayed inhibition of ouabain-sensitive QO2 and nystatin-stimulated QO2, indicative of Na+, K(+)-ATPase inhibition, was observed after 30 sec of exposure to Hg2+. More prolonged treatment (2 min) of the tubules with Hg2+ resulted in a 40% reduction in the CCCP-uncoupled QO2, indicating delayed injury to the mitochondria. The net K+ efflux was mimicked by the sulfhydryl reagents pCMBS and N-ethylmale-imide (10(-4) M) and prevented by dithiothreitol (DTT) or reduced glutathione (GSH) (10(-4) M). In addition, both DTT and GSH immediately reversed the Ag(+)-induced net Ca2+ uptake. Thus, sulfhydryl-reactive heavy metals cause rapid, dramatic changes in the membrane ionic permeability of the proximal tubule before disrupting Na+, K(+)-ATPase activity or mitochondrial function. These alterations appear to be the result of an interaction of the metal ions with sulfhydryl groups of cell membrane proteins responsible for the modulation of cation permeability. PMID- 2304070 TI - Prostaglandin E2 enhances the sodium conductance of exocrine glands in isolated frog skin (Rana esculenta). AB - Prostaglandins are known to stimulate the active transepithelial Na+ uptake and the active secretion of Cl- from the glands of isolated frog skin. In the present work the effect of prostaglandin E2 (PGE2) on the glandular Na+ conductance was examined. In order to avoid interference from the Na+ uptake and the glandular Cl secretion the experiments were carried out on skins where the Cl- secretion was inhibited (the skins were bathed in Cl- Ringer's solution in the presence of furosemide, or in NO3- Ringer's solution), and the active Na+ uptake was blocked by the addition of amiloride. Transepithelial current, water flow and ion fluxes were measured. A negative current was passed across the skins (the skins were clamped at -100 mV, basolateral solution was taken as reference). When PGE2 was added to the skins under these experimental conditions, the current became more negative; this was mainly due to an increase in the Na+ efflux. Together with the increase in Na+ efflux a significant increase of the water secretion was observed. The water secretion was coupled to the efflux of Na+, and when one Na+ was pulled from the basolateral to the apical solution via this pathway 230 molecules of water followed. From the data presented it is suggested that this pathway for Na+ is confined to the exocrine glands. PMID- 2304071 TI - Cl- transport in basolateral renal medullary vesicles: I. Cl- transport in intact vesicles. AB - This paper provides the results of studies which characterized conductive 36Cl- flux in basolaterally enriched membrane vesicles prepared from rabbit renal outer medulla. Conductive 36Cl- uptake was studied under two different experimental conditions. In the first, 36Cl- flux was driven by an inside positive voltage created with oppositely directed Cl- and gluconate gradients. In the second, an inwardly direct K+ gradient was used to drive 36Cl- uptake. By these two methods, voltage-sensitive 36Cl- uptake was shown to comprise about 45 and 65%, respectively, of the initial rates of total 36Cl- flux. Separate paired studies demonstrated that the conductive 36Cl- uptake was inhibited by the Cl- channel blocker diphenylamine-2-carboxylate (DPC) with an IC50 for DPC of 154 microM. The voltage-dependent 36Cl- uptake had an activation energy of 6.4 kcal/mole. This 36Cl- conductance had an anion selectivity sequence of I- greater than Cl- greater than or equal to NO3- much greater than gluconate. PMID- 2304074 TI - Hemobilia presenting as lower gastrointestinal hemorrhage without pain or jaundice: a case report. AB - Hemobilia is a rare source of gastrointestinal (GI) hemorrhage. When hepatobiliary bleeding presents as GI bleeding, a history of preceding blunt abdominal trauma is reported in approximately 50% of cases. Often three to four weeks have elapsed between the injury and presentation, and as long as twelve weeks has been reported. Symptoms may suggest either upper or lower GI blood loss. Traumatic hemobilia is commonly associated with cavitary injuries to the liver, and is classically characterized by a triad of findings: GI bleeding, biliary colic, and jaundice. This report describes a patient with traumatic hemobilia, who had neither a significant hepatobiliary injury, nor the classic triad of findings. PMID- 2304075 TI - HIV testing in Mississippi: questions doctors ask. PMID- 2304072 TI - Action of diphtheria toxin does not depend on the induction of large, stable pores across biological membranes. AB - Vero cells exposed to diphtheria toxin at pH 4.5 leak monovalent cations but not amino acids or phosphorylated metabolites; affected cells do not take up trypan blue. Monovalent cation leakage is inhibited by 1 mM Cd2+, but not by 1 mM Zn2+ or Ca2+. Cd2+ blocks calcein leakage from liposomes and closes diphtheria toxin induced channels in lipid bilayers. It is concluded that translocation of the A fragment of diphtheria toxin across biological membranes does not depend on the formation of large stable pores, but that small Cd2(+)-sensitive pores may play a role. PMID- 2304073 TI - Increase in gap junction resistance with acidification in crayfish septate axons is closely related to changes in intracellular calcium but not hydrogen ion concentration. AB - Neutral-carrier pH- and Ca-sensitive microelectrodes were used to investigate the relationship between junctional electrical resistance and either pHi or [Ca2+]i in crayfish septate axons uncoupled by acidification. For measuring [Ca2+]i a new neutral carrier sensor sensitive to picomolar [Ca2+] and virtually insensitive to other ions was used. Uncoupling was induced by superfusing the axons with Na acetate solutions (pH 6.3). With acetate, the time course of changes in junctional resistance differed markedly from that of pHi or [H+]i, and [H+]i peaked 40-90 sec before junctional resistance. The difference in shape and peak time between pHi and junctional resistance curves caused significant hysteresis in the pHi versus junctional resistance relationship. In addition, junctional resistance maxima reached with slow acidification rates were 3-4 times greater than those with fast acidification of similar magnitude. With acetate, [Ca2+]i increased by approximately one order of magnitude from basal values of 0.1-0.3 microM. The curves describing the time course of changes in [Ca2+]i and junctional resistance matched well with each other in shape, peak time and magnitude. Both junctional resistance and [Ca2+]i recovered following a single exponential decay with a time constant of approximately 2 min. Different rates of acidification caused increases in [Ca2+]i and junctional resistance comparable in magnitude. The data indicate that the increase in junctional resistance induced by acidification is more closely related to [Ca2+]i than to [H+]i. PMID- 2304076 TI - Collective negotiation and antitrust: Part 2. What can physicians and medical societies do? PMID- 2304077 TI - 1990--a time for change. PMID- 2304079 TI - Radiological seminar CCXLIV: Wegener's granulomatosis. AB - This case was a typical presentation for Wegener's granulomatosis with respect to the pulmonary and renal findings. Over the course of the past ten years this patient has done relatively well with only two major exacerbations requiring hospitalization. His renal function has apparently not been compromised to date. The finding of limited or no significant upper respiratory involvement is interesting in this case and is rather atypical for this disease. This may well represent a limited variant of Wegener's granulomatosis or possibly an excellent response of the Wegener's syndrome to cytotoxic chemotherapy. Finally, this case illustrates how appropriate clinical and pharmacological management has greatly improved the morbidity and mortality of this once uniformly fatal disease. PMID- 2304078 TI - Regulations prohibiting abortion counseling held unconstitutional. PMID- 2304080 TI - Management of toxic shock syndrome. PMID- 2304081 TI - Erythropoietic bone marrow in the pigeon: development of its distribution and volume during growth and pneumatization of bones. AB - During postnatal development of the pigeon, a large portion of the skeleton becomes pneumatized, displacing the hemopoietic bone marrow. The consequences of pneumatization on distribution and quantity of bone marrow as well as the availability of other sites for hemopoiesis have been investigated. Hemopoietic marrow of differently aged pigeons divided into five groups from 1 week posthatching (p.h.) up to 6 months p.h. was labeled with Fe-59 and examined by serial whole-body sections. Autoradiography and morphometry as well as scintillation counts of single bones and organs were also carried out. No sign of a reactivation of embryonic sites of erythropoiesis was found. Bone marrow weight and its proportion of whole-body weight increased during the first 4 weeks p.h. from 0.54% to 2.44% and decreased in the following months to about 1.0%. The developing bone marrow showed a progressive distribution during the first months of life, eventually being distributed proportionally over the entire skeleton, except for the skull. At the age of 6 months p.h. bone marrow had been displaced, its volume decreasing in correlation to increasing pneumaticity and conversion to fatty marrow. This generates the characteristic pattern of bone marrow distribution in adult pigeons, which shows hemopoietic bone marrow in ulna, radius, femur, tibiotarsus, scapula, furcula, and the caudal vertebrae. PMID- 2304082 TI - Dermal extracellular lipid in birds. AB - A light and electron microscopic study of the skin of domestic chickens, seagulls, and antarctic penguins revealed abundant extracellular dermal lipid and intracellular epidermal lipid. Dermal lipid appeared ultrastructurally as extracellular droplets varying from less than 1 micron to more than 25 microns in diameter. The droplets were often irregularly contoured, sometimes round, and of relatively low electron density. Processes of fibrocytes were often seen in contact with extracellular lipid droplets. Sometimes a portion of such a droplet was missing, and this missing part appeared to have been "digested away" by the cell process. In places where cells or cell processes are in contact with fact droplets, there are sometimes extracellular membranous whorls or fragments which have been associated with the presence of fatty acids. Occasionally (in the comb) free fat particles were seen in intimate contact with extravasated erythrocytes. Fat droplets were seen in the lumen of small dermal blood and lymph vessels. We suggest that the dermal extracellular lipid originates in the adipocyte layer and following hydrolysis the free fatty acids diffuse into the epidermis. Here they become the raw material for forming the abundant neutral lipid contained in many of the epidermal cells of both birds and dolphins. The heretofore unreported presence and apparently normal utilization of abundant extracellular lipid in birds, as well as the presence of relatively large droplets of neutral lipid in dermal vessels, pose questions which require a thorough reappraisal of present concepts of the ways in which fat is distributed and utilized in the body. PMID- 2304083 TI - Embryonic and neonatal development of the vomeronasal and olfactory systems in garter snakes (Thamnophis spp.). AB - Newborn, unfed garter snakes (Thamnophis spp.) respond preferentially to aqueous extracts of natural prey items, and these responses are mediated by the vomeronasal system (VNS). Since the VNS, and possibly the olfactory system (OS), are functional at birth, we examined the ontogeny of VNS and OS structures in four embryonic stages and two postnatal ages in garter snakes. The results of this study show 1) significant changes in thickness of the receptor epithelia for both systems; 2) temporal differences in the innervation of the telencephalon for each system; and 3) concurrent development of primary and secondary projection sites in both systems. Possible interactions between different cell populations and their significance for morphogenesis are discussed. PMID- 2304084 TI - External morphology of the antennae of Damalinia ovis (Phthiraptera: Trichodectidae). AB - The antennae of adult Damalinia ovis, the sheep louse, were studied using light and scanning electron microscopy. Sensory structures are located on all three antennal segments with the predominant sensilla type being tactile. Nine different types of sensilla are described on the basis of external appearance. One of the sensilla, designated a "pit organ" because of its unusual shape, has not been described previously. A pair of these sensilla are present on each antenna, and their function is unknown. A group of 11 sensilla on the tip of each antenna contains olfactory and chemosensory pegs, and a possible thermohygroreceptor. The antennae are sexually dimorphic, the male having more tactile sensilla, two well-developed terminal hooks, and a different cuticular architecture on the posterior surface of antennal segment 1. PMID- 2304085 TI - Weight gain in breast cancer patients: a problem? PMID- 2304086 TI - Effects of reoxygenation on cells from hypoxic regions of solid tumors: anticancer drug sensitivity and metastatic potential. AB - Tissue hypoxia in regions of solid tumors has been identified as a factor that may affect the behavior of cancer cells. In this study, cells were isolated from hypoxic regions of transplanted murine tumors and tested for sensitivity to anticancer drugs and ability to form experimental metastases. The tumors studied were KHT-C2-LP1 fibrosarcoma and SC-CVII squamous cell carcinoma in C3H mice and B16F10-A1 melanoma in C57BL mice. Our results indicate that the position of tumor cells relative to the vasculature, which determines the degree of tissue oxygenation, does not influence the in vitro sensitivity of cells to either doxorubicin or methotrexate. Conversely, 1-2 days after reoxygenation by introduction into culture, subpopulations of tumor cells demonstrated a transient increase in lung colonization ability. The most hypoxic cells exhibited a metastatic efficiency that was generally twice that of cells from well-oxygenated regions. This behavior is similar to behavior we observed in a previous study when tumor cells were exposed in vitro to conditions of extreme hypoxia. The findings in that study suggested that gene amplification associated with DNA over replication is responsible for the enhanced metastatic potential, but we found no indication in the present study that gene amplification was involved in the effect observed with the hypoxic tumor subpopulations. These results provide additional evidence that reoxygenated cancer cells have a high colonization ability and that these cells may be important in the formation of distant metastases. PMID- 2304087 TI - Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. AB - Although the serum level of carcinoembryonic antigen (CEA) is directly associated with a poor prognosis in human colorectal carcinoma (CRC), its function is obscure. As a member of the immunoglobulin supergene family, CEA may be involved with intercellular recognition and binding and facilitate attachment of CRC to sites of metastasis. In an experimental metastasis model of CRC in athymic nude mice, a systemic injection of CEA enhanced experimental liver metastasis and implantation in liver by a weakly metastatic CRC. This CRC also selectively bound to CEA that was attached to plastic. Thus, CEA may function as an attachment factor for CRC. PMID- 2304088 TI - Nude rat model for studying metastasis of human tumor cells to bone and bone marrow. AB - Bone metastases reproducibly developed in nude rats after an injection of LOX human malignant melanoma cells into the left ventricle, with hind leg paralyses appearing in all animals within approximately 2 weeks. Manifest metastases were present exclusively in the skeletal system, predominantly in the lumbar portion of the spine, the long bones, and occasionally in the skull. Intracardially injected 125I-labeled tumor cells and monodisperse microspheres were distributed in parallel to the various tissues. Moreover, because the levels of radioactivity were significantly lower in bone than in lung, kidney, and liver, the pattern of metastases could not be explained solely by hemodynamic factors. In chemotherapy experiments, the survival time of rats given left ventricular injections of LOX cells increased in a dose-dependent manner after the animals were treated with dacarbazine. Researchers may find the model useful for studying the biology of bone metastases and for testing the sensitivity of these lesions to drugs. PMID- 2304089 TI - Mechanisms of endocrine dysfunction in patients with testicular cancer. AB - To determine mechanisms of endocrine dysfunction in patients with testicular cancer, we performed static and dynamic testing of the hypothalamic-pituitary testicular axis and testicular exocrine function in 13 patients and 11 normal control subjects, as well as in vitro studies of tumor tissue and remaining adjacent "normal" testicular tissue in the 13 patients. In tumor tissue, we demonstrated (a) elevated concentrations of total serum estradiol and serum estradiol not bound to sex hormone-binding globulin, (b) impaired spermatogenesis and sperm motility, and (c) blocking of multiple enzymes necessary for steroidogenesis. The data were consistent with a paracrine-endocrine mechanism in which tumor-produced human chorionic gonadotropin stimulates production of estradiol by "normal" testicular tissue but not tumor tissue, and the high estradiol levels then result in impaired spermatogenesis. PMID- 2304090 TI - Effect of exposure to calcium entry blockers on doxorubicin accumulation and cytotoxicity in multidrug-resistant cells. AB - Flow cytometry has been used to measure doxorubicin (DOX) retention in several pairs of drug-sensitive and multidrug-resistant (MDR) cell lines and in unselected human tumor cell lines. Co-exposure to several agents that have been reported to reverse multidrug resistance, particularly calcium entry blockers (CEBs), produced a dose-dependent increase in DOX accumulation in MDR cell lines. In MDR Chinese hamster ovary cells (CHRC5), DOX levels declined rapidly following removal of CEBs, reaching a plateau value above that found in cells treated with DOX alone; this small increase probably represents DOX that is not accessible to the p170 efflux pump overexpressed in these cells. Increased DOX retention could be observed even after brief exposure to CEBs and washout and correlates with a decrease in cell proliferation over a 3-day growth assay. These results suggest that only a brief inhibition of drug efflux is sufficient to produce a meaningful reversal of drug resistance. PMID- 2304091 TI - N-myc gene amplification in teratoma. PMID- 2304092 TI - Acute leukemia following cisplatin-based chemotherapy in a patient with ovarian cancer. PMID- 2304093 TI - Should mind-altering substances be legalized? PMID- 2304094 TI - The effect of family violence on children's academic performance and behavior. AB - Homicide perpetrated by an acquaintance or a close family member is the leading cause of death among blacks. Black children adversely affected by these violent occurrences suffer posttraumatic stress disorder. The purpose of this study is to illustrate how damage caused to black children from exposure to violence is reflected in behavior problems and poor school performance. PMID- 2304095 TI - Incidence of Legionella pneumophila infections among Oklahoma pulmonary disease patients. AB - Prior studies by the authors suggested high levels of Legionella pneumophila in the recreational and water supply reservoirs in central Oklahoma. This high exposure potential was supported by a relatively high prevalence of seropositive, asymptomatic infections among healthy blood donors in the area. In contrast, the present 9-month laboratory-based study confirmed only one clinical Legionella infection among 117 unidentified pulmonary disease patients admitted to the Oklahoma City Veterans Administration Medical Center. Comparison with the reports of others and with reported legionellosis in Oklahoma indicates that differences in cohort definition and variations in utilization and interpretation of clinical analyses leads to wide variations in the reported incidence of legionellosis. PMID- 2304096 TI - Serial evaluation of iron stores in pregnant Nigerians with hemoglobin SS or SC. AB - Iron status of nonpregnant and pregnant Nigerian patients with hemoglobin SS or SC were assessed using serial hematological parameters, measured by Coulter counter, and serial serum ferritin concentrations measured by radioimmunoassays. The median value of 393 micrograms/L (range, 175 to 900 micrograms/L) for serum ferritin in nonpregnant patients with Hb SS and SC was significantly higher than that found in nonpregnant patients with Hb AA (median, 89.8 micrograms/L; range, 13 to 250 micrograms/L). Apart from packed cell volume values, there were no other significant differences between patients with Hb SS or SC and Hb AA in the other parameters assessed: mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In both the normal pregnant patients (Hb AA) and pregnant patients with Hb SS and SC the serum ferritin values decreased as pregnancy advanced to 28 weeks and rose gradually thereafter. At similar stages of gestation serum ferritin values were significantly higher in patients with Hb SS or SC than in those with Hb AA. Pregnancy seems to have induced a significant rise in mean corpuscular volume and mean corpuscular hemoglobin values in the patients with Hb SS or SC, especially in the third trimester, than in patients with Hb AA. The pattern of change in mean corpuscular hemoglobin concentration values was similar in both groups of patients. From the data obtained, it seems the iron status in the patients with Hb SS or SC was good, and pregnancy did not push the patients into an iron deficiency state. The use of prophylactic iron supplementation in pregnant patients with Hb SS or SC appears unjustified. PMID- 2304097 TI - Guidelines for the CME moderator. AB - Although an essential part of the continuing medical education program, the moderator is seldom mentioned in the literature when program preparation and evaluation are discussed. One result of such neglect could be the perception of the moderator as one who merely introduces the speaker and monitors the time and questions. The purpose of this article is to provide some useful guidelines that should enable the Moderator to become more cognizant of the role and responsibilities. Such guidelines are especially essential for the moderator at a National Assembly where the program planner may not always be readily available. PMID- 2304098 TI - Isoniazid toxicity presenting as seizures and metabolic acidosis. AB - The presenting signs and symptoms of isoniazid toxicity are discussed, with a review of the complications and management of this metabolic encephalopathy with B6 pyridoxine. This study supports previous studies in finding that ingestion of more than 80 mg/kg body weight produces severe central nervous system symptoms that are rapidly reversed with intravenous administration of pyridoxine. PMID- 2304099 TI - Radiation therapy alone versus radiation therapy and chemotherapy in the management of Hodgkin's disease. AB - Forty-four patients with histologically proven Hodgkin's disease underwent initial treatment with extended-field radiation therapy. Nineteen of these patients also received combination chemotherapy. For analysis, patients were assigned to three treatment groups: group 1 received radiation therapy only (25 patients); group 2 received combination chemotherapy followed by consolidative (low-dose extended-field) radiation therapy; and group 3 was treated with alternate chemotherapy and radiation therapy using the sandwich technique. The actuarial 5-year disease-free survival rates were 83% (group 1), 83% (group 2), and 100% (group 3). The overall actuarial survival rates were 96% (group 1), 92% (group 2), and 100% (group 3). No factor was identified as being of prognostic value in predicting relapse. We conclude that extended-field radiation therapy delivered in this manner is a safe and effective approach to the initial management of Hodgkin's disease. PMID- 2304100 TI - Stab wounds to the chest: a retrospective review of 100 consecutive cases. AB - In a retrospective review of 100 consecutive cases of stab wounds to the chest, 44 patients were successfully treated with tube thoracostomy, 14 patients required thoracotomy, 17 patients with small pneumothoraces were observed, and 25 patients were asymptomatic. The overall mortality was 4%, operative mortality was 7.1%, and the mortality rate for cardiac injuries was 50%. Of the eight patients with cardiac injuries, three were dead on arrival to the hospital and one patient died in the operating room. Patients treated with tube thoracostomy had a shorter hospital stay than patients managed by observation alone. Our findings support the opinion that asymptomatic patients (normal chest x-rays) may be discharged after 24 hours of observation and asymptomatic patients with nonprogressive small pneumothoraces (less than 20%) not requiring a chest tube may be discharged after 48 hours of observation. All patients should have close outpatient follow-up. PMID- 2304101 TI - Self-induced hematuria. AB - Two patients, an adult and a child, are reported who presented with factitious hematuria secondary to self-induced finger sticks with contamination of unwitnessed urine samples. Feigned illness of this kind may be more common than generally appreciated. PMID- 2304102 TI - Hyperthyroid hypokalemic periodic paralysis in a Hispanic male. AB - A case of hyperthyroid periodic paralysis in a Hispanic male is reported, the disorder in this race being described only once before. He presented with complete paralysis below the neck, and his admission potassium of 1.3 mEq/L is the lowest reported in the literature. Correction of the hypokalemia resolved his symptoms. Radionuclide imaging and thyroid function tests revealed the presence of hyperthyroidism which was managed medically. The pathophysiology of hyperthyroid hypokalemic periodic paralysis is discussed. PMID- 2304103 TI - Victimization of black psychiatric patients. PMID- 2304104 TI - The Meharry Hubbard and Nashville General Hospital merger proposal statement. PMID- 2304105 TI - Diversity in medical education and health care access: after the '80s, what? PMID- 2304106 TI - Emergency room use by patients from the family practice of a black physician. AB - Lack of access to a primary care physician has been cited as a major influence on the patterns of emergency department use by low income patients. This study, however, clearly suggests that some other, equally important, variables influence this problem. Seven hundred ninety-four visits to the emergency department during 1980 by patients from the practice of a minority physician were reviewed. The study supported other reports of frequent and inappropriate use of the emergency department by welfare patients, in spite of the availability of the family physician. The high percentage of nontrauma-related visits, especially in the age group of 20 to 30 year olds, strongly suggests the influence of sociocultural factors in this occurrence. Although further study is necessary, investigators must be cautious that the complexity of the situation could belie any quick fix. PMID- 2304107 TI - Geriatric blunt multiple trauma: improved survival with early invasive monitoring. AB - Geriatric trauma survival rates are reported to approach 85%, but no series to our knowledge has included a predominance of multiply injured patients. In 1985, we treated 60 patients more than 65 years of age who sustained blunt multiple trauma, excluding burns and minor falls. A pedestrian-motor vehicle mechanism, initial BP less than 150 mm Hg, acidosis, multiple fractures, and head injuries all predicted mortality. To investigate this, in 1986, we began invasive monitoring in all patients with any of these risk factors and modified this in 1987 to emergent monitoring, postponing all but the most critical diagnostic studies. All patients included were hemodynamically stable after initial evaluation. Attempts were made to optimize all patients with volume, inotropes, and afterload reduction as needed. There was no difference between 1986 and 1987 in patient age, injury severity, or per cent of patients requiring operation. In 1986, mean time from ED admission to monitoring was 5.5 hours. Eight of 15 patients had an initial cardiac output (CO) less than 3.5 L/M and/or mixed venous saturation (MVO2) less than 50%. All developed progressive pump failure despite therapy and died within 24 hours. The other seven had an initial CO between 3.4 5.5 L/M, but five had an MVO2 less than 50%. All augmented their CO with therapy over 6-12 hours to a mean CO of 6.8 L/M and resolved their MVO2, but six died from MOF. Survival was 7%. In 1987-88, we reduced time to monitoring to 2.2 hours by limiting diagnostic tests. Thirteen of 30 patients treated had an initial CO less than 3.5 L/M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304108 TI - Males as a high-risk group for trauma: the Finnish experience. AB - The high incidence of trauma among young men has been observed in many countries. To better understand this risk, we analyzed male injuries and their causes in Finland. The incidence peak of medically attended trauma in men aged 15-24 years was caused by occupational and sports injuries, whereas that of hospitalizations was due to motor vehicle injuries. Age patterns of nonfatal trauma resembled those recorded in the U.S.A. However, patterns and causes of fatal trauma were very different in the two countries: early adulthood in the U.S.A. and late middle-age in Finland were the ages of highest injury mortality. The majority of deaths in young men were caused by motor vehicle injuries in the U.S.A., whereas suicides and the extremely high rate of fatal non-motor vehicle accidents, largely due to alcohol poisoning and drownings, formed the main bulk of injury mortality in Finland. Similarities in early adulthood suggest general biological factors, whereas the deviance of the middle-aged male Finns from the general pattern may indicate more specific psychosocial factors. PMID- 2304109 TI - Fatal hepatic hemorrhage: an unresolved problem in the management of complex liver injuries. AB - The operative records of 683 patients who required an exploratory laparotomy for trauma with the findings of a liver injury were reviewed. Of the 683 patients 18% (121) sustained severe liver injuries with difficult to control hemorrhage, and 82% of the deaths, in this group of severe liver injuries, were due to exsanguination. A critical analysis of the specific surgical techniques used for hemostasis was undertaken. Hepatotomy with subsequent direct vascular and/or biliary duct repair or ligation was used in 44% of the cases and was successful 87% of the time. Hepatic resection was employed in 10% of the cases with a 50% mortality. Liver packs were used in 29% of the cases which included 14 hepatic vein and six retrohepatic vena caval injuries and five extensive bilobar parenchymal disruptions. The survival rate for this group of patients was 86%. Vascular isolation of the liver was used 8.3% of the cases and was successful 40% of the time. An algorithm for the successful surgical control of hemorrhage from severe liver injuries including indications and contra-indications of specific surgical techniques is presented. PMID- 2304110 TI - Smoke inhalation injury and the effect of carbon monoxide in the sheep model. AB - The role of carbon monoxide (CO) in causing the physiologic and anatomic changes characteristic of smoke inhalation injury was evaluated in 34 sheep. The smoke exposed group received a dose of smoke known to produce mild inhalation injury. The CO group received a pure gas mixture that contained concentrations of oxygen, carbon dioxide, and CO similar to those in the smoke. Cardiopulmonary function was measured immediately after exposure, and 24 and 72 hours after exposure. The CO group showed a transient increase in cardiac output, but the smoke group showed no such response. The CO group maintained normal PaO2 levels during the 72 hour study period; the smoke group gradually developed hypoxemia. The lungs of the CO exposed animals had no discernible histologic changes; lungs of the smoke group showed progressive inflammatory changes. These results indicate that CO per se is not the primary etiologic agent of smoke inhalation injury. PMID- 2304111 TI - Characteristics of blunt and personal violent injuries. AB - This study was designed to analyze the characteristics and behavior patterns of individuals involved in nonfatal, traumatic injuries. There were 547 patients included in the study with 363 sustaining blunt trauma injuries, 144 sustaining personal violence injuries, and 40 being burn victims. Motor vehicle accident victims tended to be young, single, white, employed males: substance use was detected in 32%, and 57% were unbelted. Motorcycle accident victims tended to be young, single, unemployed males: substance use was detected in 25% and 90% were not wearing helmets. Pedestrians struck tended to be single, unemployed males. Penetrating injuries involved mostly young, single, black males: substance use was detected in 35% of patients and most incidents occurred from 4:00 P.M. to 8:00 A.M. Assault victims were mostly young, single, black males with substance use detected in 48%. Suicide patients tended to be white males. The incidence of repeat victims was one out of ten for blunt trauma, and one out of five for personal violence injuries and burns. PMID- 2304112 TI - Arrow wound management in Papua New Guinea. AB - Arrow injuries sustained during tribal fighting are a common reason for admission to the hospitals of Southern Highlands Province in Papua New Guinea (P.N.G.). The authors, Canadian and American family physicians with an aggregate 12 years' general practice experience in the P.N.G. Highlands, present the findings of a 1 year retrospective study of arrow wound victims admitted to two hospitals. Arrow wound injuries are a consequence of a variety of sociocultural factors that continue to result in their high incidence despite many decades of contact with the outside world. We present the details of the presentation and management of 90 cases including a preponderence of soft-tissue as well as intracranial, thoracic, and abdominal injuries. Illustrative case histories of the more challenging or unusual cases provide insight into the unique opportunity afforded the general practitioner/surgeon in managing a type of injury which has become virtually extinct in North American practice over the last 200 years. PMID- 2304113 TI - Intra-abdominal seatbelt injury. AB - The use of seatbelts has significantly decreased the mortality and morbidity of injuries caused by motor vehicle accidents. We present eight patients who sustained severe intra-abdominal injuries peculiar to the use of the seatbelt. Serious injuries to the bowel and mesentery may be present without early symptoms or physical signs and neither CT scanning nor diagnostic peritoneal lavage is fully reliable or accurate in finding the injury. Prompt diagnosis may be difficult and requires a high index of suspicion as well as a determined approach that may include exploratory celiotomy. The presence of a seatbelt sign across the abdomen is not incontrovertible evidence that a laparotomy must be done, but its presence should create a high index of suspicion for serious visceral injury. Delay in diagnosis significantly increases morbidity and is associated with high mortality rates. PMID- 2304114 TI - Features of head injury in a developing country--Taiwan (1977-1987). AB - Certain features of head-injured patients admitted to the Chang Gung Memorial Hospital in Taiwan during the period 1977 to 1987 were reviewed. The most common causes of injury were motorcycle accidents (56.3%) and street accidents with pedestrian injury (29.47%). The age groups with the greatest incidence of injury were aged 16-20 years, 21-25 years, and 25-30 years. The pedestrian group involving the highest incidence of injury was less than 10 years of age. Overall mortality was 17.26%. The injured pedestrian group had the highest mortality (19.1%). Initial clinical assessment was recorded using the Glasgow Coma Scale. Head-injured patients with a GCS less than 8 had a mortality in the injured pedestrian group of 46%, whereas the mortality rate in the motorcycle accident group was 41%. Additional features studied were time of occurrence of injury and pattern of injury. Information gathered from this study would suggest the need to establish a Head Injury Prevention Program in Taiwan. This of course implies major cooperation among the providers of health care delivery, the medical profession, legislators, and the government at all levels. PMID- 2304115 TI - Implications of admission hypothermia in trauma patients. AB - Hypothermia is common after severe injury, and has been associated with an increased mortality rate in patients stratified by anatomic indices of injury severity. In this retrospective study of 173 patients, early post-traumatic hypothermia was found to correlate with physiologic indicators of volume deficit, independently of the amount of intravenous fluid received. There was no correlation found between admission core temperature and time from injury, blood alcohol, or presence of severe closed head injury. Hypothermic patients (less than 35 degrees C) had a lower predicted probability of survival and a higher mortality rate than euthermic patients (greater than or equal to 35 degrees C). However, when patients were stratified by physiologic and anatomic indicators of injury severity, mortality rates among the euthermic and hypothermic patients were not significantly different. Early post-traumatic hypothermia does not appear to exert an independent effect upon outcome. PMID- 2304116 TI - Cardiac injuries--a clinical and autopsy profile. AB - One hundred two patients sustaining cardiac injuries over a 4-year period were analysed to highlight the natural history of the cardiac injuries. There were 45 blunt, 36 stab, and 21 gunshot injuries. The injury involved the ventricle in 85, atrium in seven, pulmonary artery in five cases, and resulted in crush injury to the heart in the remaining five cases. Thirty-three patients (32.3%) died on the scene and 58 (56.9%) died during the transportation. Only 11 patients (10.8%) reached the hospital alive, and ten of these patients survived following thoracotomy and repair of the cardiac injury. The factors influencing the natural course of cardiac injury were analysed: 2.2% of patients with blunt cardiac trauma reached the hospital alive compared to 19.4% with stab and 14.3% with gunshot injuries; ventricular injuries had a greater prehospital mortality compared to atrial or pulmonary artery injuries; 11.3% of patients sustaining injury to right ventricle reached the hospital alive compared to 3% of those with left ventricular injuries. These data emphasize the need for rapid transport, immediate recognition, and aggressive surgical management, to make a favourable impact on the natural history of cardiac injuries. PMID- 2304117 TI - Genetic basis of resistance to trauma in inbred strains of mice. AB - In this study the resistance to mechanical, thermal, and radiation trauma in four inbred strains of mice (AKR, BALB/c, CBA, and C57Bl/6) was compared with the degree of genetic resemblance, by analyzing the allozyme variabilities of these strains. It was shown that the highest degree of genetic resemblance was among CBA and AKR strains, which correlated with a similar degree of resistance to trauma. On the other hand, BALB/c and C57Bl/6 strains expressed significant differences, both genetically and with respect to the responses to trauma. The hypothesis is introduced that the genetic determination of the resistance to trauma is based on: a) a polygenic control of general physiological homeostasis, with the possibility that b) some specific genes or single loci may contribute more than others to such adaptations of the strains tested. PMID- 2304118 TI - Rupture of the distal thoracic esophagus following blunt trauma: case report. AB - Rupture of the distal thoracic esophagus is an unusual injury following blunt abdominal trauma. We recently encountered this injury in a patient following a relatively minor motor vehicle accident. An improperly positioned seatbelt was presumed contributory in this case. Prevention of further contamination and drainage of infection are primary objectives. Wide mediastinal drainage with repair, resection, or diversion are recommended, depending on the degree of mediastinitis present. PMID- 2304119 TI - Post-traumatic inferior vena caval thrombosis: case report. AB - Thrombosis of the aorta and inferior vena cava is a rare sequela of blunt abdominal trauma. Inferior vena caval thrombosis developed in a 55-year-old man after blunt abdominal trauma. It was detected 18 days after injury through the use of computed tomography. The patient was treated with a Greenfield filter and anticoagulation. PMID- 2304120 TI - Myelopathy due to hypertrophic nonunion of the dens: case report. AB - Fractures which occur near the base of the dens have a low propensity to unite spontaneously. One of the major complications of nonunion is displacement of the fracture resulting in neuraxis compression and the development of myelopathy. Hypertrophic nonunion of the dens may cause spinal cord compression even if displacement does not occur. This situation has not to our knowledge previously been reported. A literature review and appraisal of the issues raised are discussed. Appropriate therapeutic options are outlined, including posterior surgery and the use of transoral decompression. PMID- 2304121 TI - External fixation of the sternum after infected dehiscence due to a shotgun wound: case report. AB - Pulmonary dysfunction and subsequent ventilator dependence may result after dehiscence of a median sternotomy if there are other complicating injuries. We report a case in which external fixation was used to achieve thoracic stability after infected dehiscence of a median sternotomy, following shotgun wound to the epigastrium. PMID- 2304122 TI - CT scan and surgical treatment of traumatic iliacus hematoma with femoral neuropathy: case report. AB - Iliacus hematoma should be suspected as the cause of femoral neuropathy in cases of minor trauma in teenagers, especially when the onset of paralysis is delayed and therefore an acute traction injury of the nerve is unlikely. In our 14-year old female patient the condition followed minor trauma. In such cases CT scan should be performed. When this reveals a hematoma and the nerve lesion is rapidly progressing or complete, the hematoma should be promptly evacuated. PMID- 2304123 TI - Incomplete femoral fracture produced by a wooden projectile: case report. AB - We report on a case of incomplete fracture of the metaphyseal portion of the femur produced by a wooden missile, a part of which remained stuck in the bone after wound management. The wooden foreign body in the bone was detected with xeroradiography and computed tomography. Complete regression of acute inflammation was achieved through removal of the wounding agent, wound debridement, and systemic and local antibiotic therapy. PMID- 2304124 TI - Traumatic avulsion of the female urethra: case report. AB - Complete rupture of the female urethra is rare. We found only 30 such cases described in the literature, 19 of which were in children. In most of these patients, the proximal urethra and bladder neck were injured. Herein we report on the complete rupture of the distal part of the urethra in a female child with a pelvic fracture. This diagnosis should be considered in such cases with deep vaginal lacerations, inability to void, and with unsuccessful catheterization. PMID- 2304125 TI - Tension pneumopericardium following penetrating trauma: case report. AB - We report a patient who developed tension pneumopericardium following penetrating trauma to the chest. Lung adhering to the pleura due to previous infection prevented the lung from collapsing and resulted in diversion of the air leak into the anterior mediastinum and from there through a breach into the pericardium. PMID- 2304126 TI - Fracture of the occipital condyle: case report and review of the literature. AB - Fracture of the occipital condyle is a rare injury. We report a patient with an occipital condyle fracture who presented with negative plain films and a cranial nerve palsy. Diagnosis was established with high-resolution computed tomography. This fracture should be considered in a trauma patient with neck pain, negative plain cervical spine radiographs, and a cranial nerve palsy. PMID- 2304127 TI - How much oral rehydration solution is actually administered during home-based therapy? AB - In some parts of the world up to one-half of all deaths in young children are attributable to dehydration associated with diarrhoea. As a countermeasure, mothers in underdeveloped countries are being successfully taught to give oral rehydration solution at home. There are, however, serious doubts as to whether mothers give their children enough. The focus of our investigation was a methodology capable of establishing the exact quantity of fluid administered by unsupervised mothers at home. Accurate quantitative data are essential for programme planning and evaluation. In our sample of 44 cases, only two children received more than 90 ml kg-1 day-1. The mean observed value was 44 ml kg-1 day-1 (SD 28.4); well below the recommended dosage. Preliminary data were also gathered on natural consequences which may discourage use of ORS such as vomiting, increased frequency of watery stools, and distaste for the solution. PMID- 2304128 TI - Malnutrition-related diabetes mellitus in young adult diabetic patients attending a Nigerian diabetic clinic. AB - Although malnutrition-related diabetes mellitus (MRDM) is reported to affect about 40-50% of young adult diabetics in the Indian subcontinent and possibly other tropical and subtropical countries, anecdotal reports have suggested its relative uncommonness in Africa. The presentation of subjects (aged 15-30 years) attending a major Nigerian diabetic clinic in 1984 was therefore reviewed. The results (i) confirm previous observations on the rarity of diabetes in young adult Africans: only 45 of a total of 756 registered diabetics presented when aged 15-30 years; (ii) indicate that classical MRDM from established clinical criteria was uncommon, affecting only about 6% of the subjects, the majority of whom were either atypically or classically insulin-dependent (about 90%), although a small proportion (about 6%) appeared non-insulin-dependent. These observations suggest that diabetes in young adult Nigerians is heterogeneous in clinical presentation and aetiopathogenesis and, furthermore, that classical malnutrition-related diabetes mellitus is rarely seen, being much the least common mode of presentation, unlike the indication of the WHO Expert Committee on Diabetes Report (1985). PMID- 2304129 TI - Study of family history among parents and siblings of Ethiopian diabetics: a preliminary report. AB - 218 diabetic probands and 300 non-diabetic controls were interviewed for history of diabetes mellitus in their parents and siblings. The prevalence of diabetes mellitus among blood relatives of probands and controls differed significantly. The study also showed that NIDDM probands had more positive family history of diabetes than IDDM ones. The overall findings of this study indicated that heredity has an important role in the genesis of diabetes mellitus in Ethiopian diabetics. PMID- 2304130 TI - Screening for brucellosis in pregnant women. AB - During a period of 6 months, 537 pregnant women from a rural area in Saudi Arabia were tested serologically for brucellosis. Of the 513 women who were tested routinely, 18 were found to have a positive titre (3.5%). Of 24 patients in whom the test was carried out because of symptoms suggestive of brucellosis, all were positive. Thirty of the 42 positive cases had titres exceeding 1:160. The incidence of abortion among pregnant women with Brucella titres less than 1:160 was 7.7% contrasting with 17.6% among those with titres above 1:160 (P less than 0.04). This observation calls for further study of the incidence of brucellosis in pregnant women in infected areas, and the connection between elevated Brucella titre and abortion. PMID- 2304131 TI - Cerebral malaria. Factors affecting outcome of treatment in a suboptimal clinical setting. AB - Over a period of 6 months, 109 patients were admitted to the medical wards of the Gondar College Hospital with malaria. Out of these, 26 patients (24.8%) had cerebral malaria as defined by the WHO Malaria Action Programme 1986. Fifteen of the 26 patients (57.7%) died. Longer duration of unconsciousness before coming to the hospital, hyperparasitaemia, oliguria, recurrent hypoglycaemia and convulsions were found to be significantly associated with mortality. PMID- 2304132 TI - A case of multiple lesion mucocutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis infection. AB - A case of leishmaniasis with multiple lesions due to Leishmania (Viannia) braziliensis infections was diagnosed in a male patient from north-east Brazil. The skin lesions were nodular and pustular and progressed to ulcers. Skin and the oral mucosae were also affected. The behaviour in culture and hamsters of the parasite recovered from a skin lesion was similar to other strains of L. (V.) braziliensis and the strain was characterized by monoclonal antibodies as belonging to serodeme I of this species. The histopathology of the skin lesions of the patient and hamster were of an inflammatory nature which extended through the dermis; leishmania in the tissues were more easily detected by the immunoenzymatic PAP method. PMID- 2304133 TI - Yaws in the Solomon Islands. AB - Yaws is a chronic, relapsing, non-venereally transmitted disease caused by Treponema pertenue. As a result of the WHO mass treatment campaign of the late 1950s, the prevalence in the Solomon Islands fell dramatically. Here the disease was thought to have been eradicated until an outbreak occurred in 1981. In 1984 a mass treatment survey following modified WHO guidelines was carried out. Subsequent to this campaign, yaws recurred and in 1987 a further treatment survey was required. Two observations were made as a result of our recent experience in controlling yaws in the Solomon Islands. (1) The disease appears to be attenuated. (2) WHO control policy may now be an inappropriate method for dealing with yaws in the Solomon Islands and should be replaced by a method which is integrated into the existing primary health care (PHC) structure. PMID- 2304134 TI - Evaluation of a primary health care programme in The Gambia. I. The impact of trained traditional birth attendants on the outcome of pregnancy. AB - In 1983 a primary health care (PHC) programme was introduced into the Farafenni area of The Gambia; an important component of this programme was the identification and training of a traditional birth attendant (TBA) in each village with a population of 400 or greater. The outcome of pregnancy has been documented among women resident in 15 villages which joined the PHC programme and in 26 which were too small to do so, for 1 year before and for 3 years after the start of the programme. In PHC villages 65% of women were assisted at delivery by a trained TBA during the post-implementation period and the proportion of women who delivered in a hospital or health centre increased. Both maternal and neonatal death rates fell in PHC villages during the post-intervention period, declining to about half the levels recorded during pre-intervention surveys during the last year of the study. In non-PHC villages there was also a fall in the maternal death rate but little change in the neonatal death rate. Trained traditional birth attendants probably played some part in improving the outcome of pregnancy in the Farafenni area but other factors, such as improvements in transport, may also have contributed. PMID- 2304135 TI - Childhood bacterial meningitis in Kuwait. AB - A total of 110 cases of bacterial meningitis were studied over a 7-year period. The attack rate was 3.2/100,000 overall and 13/100,000 in children under 12 years. Haemophilus influenzae was the most common pathogen (44.3%), followed by Streptococcus pneumoniae (20.9%) and Neisseria meningitidis (12.7%). The mean patient age was 2.7 years, but 44/49 cases of H. influenzae meningitis were in children under 2 years, an attack rate of 31/100,000. The mortality was 22.4% for neonates and 6.5% for other children, and was associated with coma at presentation and unusual microorganisms. Neurological sequelae were detected in 19% of surviving children. PMID- 2304136 TI - A specific base transition occurs on replicating hepatitis delta virus RNA. AB - Three independent lines of evidence showed that when an infectious clone of hepatitis delta virus of known sequence was used to initiate genome replication, up to 41% of the genomes were specifically mutated in the amber termination codon (UAG to UGG) for the open reading frame of the delta antigen, thereby increasing the length of the predicted protein from 195 to 214 amino acids. This change was detected only on molecules that participated in RNA-directed RNA synthesis. PMID- 2304137 TI - Class I H-2d-restricted cytotoxic T lymphocytes recognize the neuraminidase glycoprotein of influenza virus subtype N1. AB - Class I major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL) that recognize the neuraminidase (NA) glycoprotein of subtype N1 influenza A viruses have been demonstrated in BALB/c mice. Responses to NA were obtained only in protocols that use two in vivo inoculations of virus, including a recombinant vaccinia virus containing the NA of subtype N1 influenza virus (NA-VAC) to prime or boost. Restimulation in vitro was also required for CTL recognition of NA and strongly depended on the specific N1 virus used. Influenza viruses A/Puerto Rico/8/34 (H1N1), A/CAM/46 (H1N1), J1 (H3N1), and JAP/BEL (H2N1), but not A/Bellamy (H1N1) or MEM/BEL (H3N1) virus, were able to stimulate NA-specific memory T cells in vitro. Single or double in vivo inoculation of any of the N1 viruses or a single injection of NA-VAC failed to elicit restimulatable NA specific CTL. Lysis of NA-VAC-infected cells at low effector/target ratios was comparable to that observed toward other influenza virus proteins known to be major targets of CTL in BALB/c mice, indicating that antigenic determinants of the subtype N1 NA molecule can be efficiently presented in the context of major histocompatibility complex class I. PMID- 2304138 TI - Construction and characterization of the recombinant Moloney murine leukemia viruses bearing the mouse Fv-4 env gene. AB - A nucleotide sequence of the mouse Fv-4 env gene was completed. Structural comparison revealed a close relationship of Fv-4 to the ecotropic Cas-Br-E murine leukemia virus isolated from a wild mouse in southern California. Various portions of the env gene of Moloney murine leukemia virus were replaced by the corresponding Fv-4 env sequence to construct recombinant murine leukemia virus clones. Infectivity of these recombinants was checked by the S+L- cell focus induction assay and the XC cell syncytium formation assay. Recombinants bearing the following Fv-4 env sequence retained ecotropic infectivity; the AccI-BamHI and BamHI-BalI regions coding for the N- and C-terminal halves of Fv-4 gp70SU, respectively; and the BalI-NcoI region encoding the cleavage site between gp70SU and p15(E)TM of the Fv-4 env. However, when the Fv-4 sequence was substituted for the p15(E)TM-coding NcoI-EcoRV region or the AccI-EcoRV region covering almost the entire env gene, infectivity was undetectable in our assays. The recombinant clone containing the Fv-4 AccI-EcoRV region, i.e., almost the entire Fv-4 env sequence, was introduced with pSV2neo into NIH 3T3 cells, and a G418r cell line named NIH(Fv4)-2 was isolated. The NIH(Fv4)-2 cell released viral particles that contained reverse transcriptase, Fv-4 env molecules as well as the other viral proteins, and viral genomic RNA. However, proviral DNA synthesis was not detected upon inoculation of this virus in NIH 3T3 cells. The loss of infectivity of the recombinant virus bearing the Fv-4 AccI-EcoRV region appeared to be caused by failure in an early step of replication. PMID- 2304139 TI - Simian immunodeficiency viruses from African green monkeys display unusual genetic diversity. AB - African green monkeys are asymptomatic carriers of simian immunodeficiency viruses (SIV), commonly called SIVagm. As many as 50% of African green monkeys in the wild may be SIV seropositive. This high seroprevalence rate and the potential for genetic variation of lentiviruses suggested to us that African green monkeys may harbor widely differing genotypes of SIVagm. To investigate this hypothesis, we determined the entire nucleotide sequence of an infectious proviral molecular clone of SIVagm (155-4) and partial sequences (long terminal repeat and Gag) of three other distinct SIVagm isolates (90, gri-1, and ver-1). Comparisons among the SIVagm isolates revealed extreme diversity at the nucleotide and amino acid levels. Long terminal repeat nucleotide sequences varied up to 35% and Gag protein sequences varied up to 30%. The variability among SIVagm isolates exceeded the variability among any other group of primate lentiviruses. Our data suggest that SIVagm has been in the African green monkey population for a long time and may be the oldest primate lentivirus group in existence. PMID- 2304140 TI - Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of west-central African origin. AB - An unusual human retrovirus was isolated from two patients with persistent generalized lymphadenopathy who originate from West-Central Africa and are currently residing in Belgium. Although the virus shared a number of the same biological and morphological properties as human immunodeficiency retrovirus type 1 (HIV-1) and HIV-2, significant antigenic differences could be demonstrated. Several of the viral proteins also differed in molecular weight from the corresponding HIV-1 and HIV-2 proteins. Partial chemical cleavage of the most highly conserved viral proteins resulted in patterns which differed from those of HIV-1 and HIV-2. Furthermore, nucleic acid hybridization experiments were capable of discriminating between the virus types. Sequence analysis of the viral U3 region revealed a unique enhancer organization not found in other immunodeficiency viruses. The data indicated that the new isolate is more closely related to HIV-1 than to HIV-2 but clearly differs in a number of important respects. PMID- 2304141 TI - Fusion function of the Semliki Forest virus spike is activated by proteolytic cleavage of the envelope glycoprotein precursor p62. AB - The precursor protein p62 of the prototype alphavirus Semliki Forest virus (SFV) undergoes during transport to the cell surface a proteolytic cleavage to form the mature envelope glycoprotein E2. To investigate the biological significance of this cleavage event, single amino acid substitutions were introduced at the cleavages site through mutagenesis of cDNA corresponding to the structural region of the SFV genome. The phenotypes of the cleavage site mutants were studied in BHK cells by using recombinant vaccinia virus vectors. Nonconservative substitutions completely abolished p62 cleavage. Uncleaved p62 was transported with normal kinetics to the cell surface, where it became accessible to low concentrations of exogenous trypsin. The proteolytic cleavage of envelope glycoprotein precursors has been shown to activate the membrane fusion potential of viral spikes in several virus families. Here we demonstrate that the fusion function of the SFV spike is activated by the cleavage of p62. Cleavage-deficient p62 expressed at the cell surface did not function in low-pH-triggered (pH 5.5) cell-cell membrane fusion; however, cleavage of the mutated p62 with exogenous trypsin restored the fusion function. We discuss a model for SFV assembly and fusion where p62 cleavage plays a crucial role in the stability of the multimeric association of the viral envelope glycoproteins. PMID- 2304142 TI - A protein serologically and functionally related to the group C E3 14,700 kilodalton protein is found in multiple adenovirus serotypes. AB - A 14.7-kilodalton protein (14.7K protein) encoded by the E3 region of group C adenoviruses has been shown to protect virus-infected fibroblasts from lysis by tumor necrosis factor (TNF) (L.R. Gooding, L.W. Elmore, A.E. Tollefson, H.A. Brady, and W.S.M. Wold, Cell 53:341-346, 1988). In this study we show that adenoviruses of other groups are also protected from TNF-induced cytolysis. Representative serotypes of groups A, B, D, and E produce a protein analogous to the 14.7K protein found in human group C adenoviruses. Deletion of this protein in group C viruses permits virus infection to induce cellular susceptibility to TNF killing. As with group C adenoviruses, cells infected with wild-type adenoviruses of other serotypes are not killed by TNF and are protected from lysis induced by TNF plus cycloheximide. However, cells are susceptible to TNF induced lysis when infected with adenovirus type 4 mutants from which the 14.7K gene has been deleted. Although all known adenovirus serotypes infect epithelial cells, adenoviruses cause several diseases with various degrees of pathogenesis. Our findings suggest that the 14.7K protein provides a function required for the in vivo cytotoxicity of many adenoviruses independent of the site of infection or degree of pathogenesis. PMID- 2304143 TI - Protein kinase A-dependent binding of a nuclear factor to the 21-base-pair repeat of the human T-cell leukemia virus type I long terminal repeat. AB - The long terminal repeat (LTR) of the human T-cell leukemia virus type I (HTLV-I) contains an imperfect repeat of 21 nucleotides which governs the response to the virus trans-activator protein tax and to cyclic AMP. In a murine thymocyte cell line defective in the catalytic subunit of protein kinase A, the response of the HTLV-I LTR to cyclic AMP is abolished and the response to tax is substantially diminished. This report shows that a factor present in nuclear extracts of wild type cells binds to the HTLV-I 21-nucleotide sequence and that this binding activity is missing from the extracts of protein kinase A-defective cells. Treatment of nuclear extracts of protein kinase A-defective cells with the bovine protein kinase A catalytic subunit restores the binding activity, whereas treatment of wild-type nuclear extracts with a protein phosphatase destroys the binding activity. The binding factor is referred to as protein kinase A-dependent factor (PKAF). These results indicate that in murine thymocytes the response of the HTLV-I LTR to cyclic AMP depends upon the binding of a phosphorylated protein to the 21-nucleotide repeat sequence and that the response to tax is partially dependent upon binding of the phosphorylated protein. The results suggest a model in which the phosphorylation of a transcription factor by protein kinase A regulates HTLV-I gene expression. PMID- 2304144 TI - Sequence variants of human T-cell lymphotropic virus type I from patients with tropical spastic paraparesis and adult T-cell leukemia do not distinguish neurological from leukemic isolates. AB - We have amplified and sequenced DNA in the envelope (env) and long terminal repeat (LTR) regions of human T-cell lymphotropic virus type I (HTLV-I) proviruses from the peripheral blood of 10 HTLV-I-seropositive patients with tropical spastic paraparesis (TSP) and two patients with adult T-cell leukemia. The aim was to examine variation in these regions and to test the hypothesis that the sequences of leukemogenic HTLV-I isolates differ from those causing the neurological disease TSP. In 5 of the 12 HTLV-I-seropositive patients, more than one HTLV-I sequence variant was identified in the same individual. No two individuals shared identical sequences in either env or LTR U3. Sequence variations were found at 73 positions in 1,416 bases amplified in env. Sequence variability was found throughout the LTR-U3 region, including the sequences of two transcriptional enhancers. Several nucleotide changes common to both Caribbean and Japanese HTLV-I isolates allowed us to identify a consensus sequence that differs from the HTLV-I prototype sequence (M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida, Proc. Natl. Acad. Sci. USA 80:3618-3622, 1983). No sequence in the env or LTR U3 region was found to be characteristic of isolates from TSP patients. Although each isolate was distinct at the nucleotide level, the predicted protein sequence of HTLV-I env is less variable than that of human immunodeficiency virus env, suggesting that these lymphotropic retroviruses use different strategies to evade host immune responses. PMID- 2304145 TI - Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen. AB - The C gene of hepatitis B virus (HBV) codes for a nucleocapsid protein made of 183 amino acid residues and is preceded in phase by the precore (pre-C) region, encoding 29 residues. The pre-C-region product is required for the synthesis and secretion of hepatitis B e antigen (HBeAg), which is made of the C-terminal 10 amino acid residues of the pre-C-region product and the N-terminal 149 residues of the C-gene product. HBV mutants with pre-C-region defects prevailed in the circulation of three asymptomatic carriers as they seroconverted from HBeAg to the corresponding antibody (anti-HBe), and these mutants finally replaced nondefective HBV. HBV DNA clones were propagated from sera of an additional 15 carriers with anti-HBe and sequenced for the pre-C region. Essentially all HBV DNA clones (56 of 57 [98%]) revealed mutations that prohibited the translation of a functional pre-C-region product. A point mutation from G to A at nucleotide 83, converting Trp-28 (TGG) to a stop codon (TAG), was by far the commonest and was observed in HBV DNA clones from 16 (89%) of 18 carriers seropositive for anti HBe. In addition, there were point mutations involving ATG codon to abort the translation initiation of the pre-C region, as well as deletion and insertion to induce frameshifts. Such mutations leading to pre-C-region defects were rarely observed in persistently infected individuals positive for HBeAg or in patients with type B acute hepatitis after they had seroconverted to anti-HBe. These results would indicate a selection of pre-C-defective mutants in persistently infected hosts, along with seroconversion to anti-HBe, by immune elimination of hepatocytes harboring nondefective HBV with the expression of HBeAg. PMID- 2304147 TI - Passively transferred monoclonal antibody to the M2 protein inhibits influenza A virus replication in mice. AB - The M2 protein of influenza A virus is expressed on the surfaces of infected cells, and a monoclonal antibody to this protein inhibits plaque enlargement of sensitive influenza A viruses without reducing plaque titer (S.L. Zebedee and R.A. Lamb, J. Virol. 62:2762-2772, 1988). In the current study, passively transferred monoclonal antibody to M2 reduced the level of replication of influenza A virus but not of influenza B virus in the lungs of mice. These experiments demonstrated that antibody to a protein conserved among influenza A virus subtypes inhibits virus growth in vivo. PMID- 2304146 TI - Vaccination with inactivated influenza A virus during pregnancy protects neonatal mice against lethal challenge by influenza A viruses representing three subtypes. AB - A single intraperitoneal injection of pregnant mice with a monovalent Formalin inactivated influenza A virus vaccine protected their offspring against a lethal challenge dose of the same influenza A virus H3N2, H2N2, and H1N1 subtypes, as well as against challenge with the other two subtypes. Degree of protection was vaccine dose related. Cross-fostering of neonates indicated that protection was conferred by breast milk antibodies. Serum virus-specific neutralizing antibodies in the mothers and neonates correlated with resistance to vaccine virus, but were detected against other subtypes only in a complement enhancement test or when high doses of vaccine were given. PMID- 2304149 TI - A temperature-sensitive mutant of Newcastle disease virus defective in intracellular processing of fusion protein. AB - A temperature-sensitive mutant (ts3) of Newcastle disease virus was physiologically characterized. All major viral structural proteins were synthesized at the permissive (37 degrees C) and nonpermissive (42 degrees C) temperatures, but the fusion (F) glycoprotein was not cleaved at 42 degrees C. In immunocytochemical electron microscopy, the F protein was abundant in the rough endoplasmic reticulum but not in cytoplasmic membrane at 42 degrees C. Noninfectious hemagglutinating virus particles containing all major structural proteins except the F protein were released at 42 degrees C from infected cells. We concluded that the defect in ts3 resides in the intracellular processing of the F protein. PMID- 2304148 TI - CD4-independent, productive infection of a neuronal cell line by human immunodeficiency virus type 1. AB - One neuronal cell line (SK-N-MC) was found to be susceptible to productive infection by multiple isolates of the human immunodeficiency virus type 1 (HIV 1). Characterization of SK-N-MC cells showed that these cells are neuroectodermal in origin in that they express dopamine hydroxylase, catecholamines, neuron specific enolase, and neurofilaments. Despite their susceptibility to HIV-1 infection, SK-N-MC cells had no detectable CD4 and this infection was not blocked by anti-CD4 monoclonal antibodies (OKT4A, Leu3A) or recombinant soluble CD4. These experiments demonstrated that certain cells of neuroectodermal origin are susceptible to infection in vitro by HIV-1 via a CD4-independent mechanism. PMID- 2304151 TI - Fungal bezoars of the upper urinary tract. AB - We report our experience with 6 cases of upper tract fungal bezoars involving 9 renal units-3 bilateral aspergillomas and 3 Candida bezoars. The Aspergillus bezoars were notably more morbid: 2 patients required nephrectomy after failure of medical therapy, whereas the 3 unilateral Candida bezoars all resolved with medical therapy and endourological access. In 1 patient whose aspergilloma was resistant to amphotericin B the investigational drug itraconazole proved effective. These opportunistic infections, seen increasingly in immunocompromised patients, can present a difficult management problem. A combined approach is necessary, including medical therapy with topical and systemic antifungal agents, and endourological access for extraction, lavage and debulking. PMID- 2304150 TI - The N-terminal (pre-S2) domain of a hepatitis B virus surface glycoprotein is translocated across membranes by downstream signal sequences. AB - The coding region for the hepatitis B virus surface antigens contains three in phase ATG codons which direct the synthesis of three related polypeptides. The 24 kilodalton major surface (or S) glycoprotein is initiated at the most distal ATG and is a transmembrane protein whose translocation across the bilayer is mediated by at least two uncleaved signal sequences. The product of the next upstream ATG is the 31-kilodalton pre-S2 protein, which contains 55 additional amino acids attached to the N terminus of the S protein. This pre-S2-specific domain is translocated into the endoplasmic reticulum. Using a coupled in vitro translation translocation system, we showed that (i) the pre-S2 domain itself lacks functional signal sequence activity, (ii) its translocation across the endoplasmic reticulum membrane is mediated by downstream signals within the S domain, and (iii) the N-terminal signal sequence of the S protein can translocate upstream protein domains in the absence of other signals. The hepatitis B virus pre-S2 protein is an example of a natural protein which displays upstream domain translocation, a phenomenon whose existence was originally inferred from the behavior of synthetic fusion proteins in vitro. PMID- 2304152 TI - The role of renal autotransplantation in complex urological reconstruction. AB - From 1972 to 1988, 108 patients underwent renal autotransplantation for renal artery disease (67), ureteral replacement (27), or renal cell carcinoma present bilaterally or in a solitary kidney (14). The most common indication for renal autotransplantation was to allow extracorporeal repair of complex branch renal artery lesions. Of the 54 patients in this group technically satisfactory branch renal arterial reconstruction and a successful clinical outcome were achieved in 52 (96%). Renal autotransplantation is the treatment of choice in these patients and also in selected children with main renal artery disease. Renal autotransplantation provided excellent results in 25 of 27 patients (92%) who required replacement of all or a major portion of the ureter. Over-all renal function was well preserved in these patients and only 1 has experienced chronic bacteriuria. Renal autotransplantation is a useful alternative to ileal interposition in this setting. Extracorporeal partial nephrectomy and renal autotransplantation were successful in 12 of 14 patients (85%) undergoing a nephron-sparing operation for renal cell carcinoma. In situ techniques are associated with less morbidity and currently are preferred in this group. PMID- 2304153 TI - Flow cytometric assessment of deoxyribonucleic acid content in renal adenocarcinoma: does ploidy status enhance prognostic stratification over stage alone? AB - Flow cytometry was used to analyze deparaffinized primary renal cell carcinoma specimens from 106 patients to evaluate deoxyribonucleic acid ploidy as a predictor of disease progression and survival. Of these specimens 62 (58%) demonstrated aneuploid stem lines: 30 (48%) of these were tetraploid aneuploid while 32 were nontetraploid aneuploid. Two or more specimens were analyzed from a single primary tumor in 17 patients and heterogeneity of ploidy status was observed in 5 (30%). Specimens of the primary tumor, and regional and/or distant metastases from 11 patients were analyzed; 5 (45%) demonstrated discordance between the ploidy of the primary and the metastatic site. A significant correlation was noted between the presence of aneuploid stem lines and high stage disease (p equals 0.004) but there was no significant correlation between ploidy status and tumor grade. Although there was a significant difference (p equals 0.037) in the incidence of disease progression in patients with diploid tumors (13%) versus those with aneuploid tumors (35%) in the total population, and Kaplan-Meier disease-specific survival curves demonstrated a survival advantage for patients with diploid tumors in the total population, no clear survival advantage was demonstrated for evaluable patients with diploid tumors when controlled for tumor, nodes and metastases stage. In conclusion, the heterogeneity of ploidy status in primary renal cell carcinoma, the high incidence of disease progression in patients with diploid primary tumors and the lack of a clearly demonstrable stage-independent impact of ploidy on prognosis currently would not support widespread clinical application of ploidy status of the primary tumor in the management of individual patients with renal cell carcinoma. PMID- 2304154 TI - Inferior vena caval invasion by renal cell carcinoma: false positive diagnosis by venacavography. AB - We reviewed the records of 22 renal cell carcinoma patients who were referred to this hospital to determine inferior vena caval extension of tumor. Preoperative radiological studies from referring hospitals and this institution were compared to the operative findings. Four cases of false positive inferior vena caval involvement on preoperative venacavograms performed and interpreted elsewhere were identified. In 3 of these cases a repeat preoperative inferior venacavogram performed at this hospital made the correct diagnosis. In the remaining case an inferior venacavogram was not repeated but no tumor was found at operation. One patient who did not undergo an operation was believed to have vena caval involvement by computerized tomography but venacavography was negative. Reasons for the false positive studies included suboptimal technique and misinterpretation of normal flow defects. Our technique for venacavography is presented. The importance of satisfactory preoperative radiological studies is stressed. PMID- 2304155 TI - Radical extensive surgery for renal cell carcinoma: long-term results and prognostic factors. AB - We studied 200 consecutive patients with renal cell carcinoma who underwent radical nephrectomy and extensive lymphadenectomy. Of the patients 25% already had distant metastasis at operation. Higher T stages tended to be associated with positive nodes (p less than 0.01) and distant metastasis (p less than 0.001). However, in patients with stage N0M0V0 tumors we found no statistically significant difference in survival in relationship to the T stage of the disease (5-year survival: stage T1 80%, stage T2 68% and stage T3 70%). Of all patients 10% had positive nodes without distant metastases and no venous spread of the tumor, and the 5-year survival rate was 52%. The 5-year survival rate of patients with distant metastases was 7%. Patient survival in the presence of a vena caval tumor thrombus is similar to that of patients with distant metastases. Based on our results the different stages in disease progression may be classified as having a good prognosis--intracapsular tumors (stages T1 to T2, N0M0V0) and tumors with involvement of perirenal fat (stage T3N0M0V0), an intermediate prognosis--tumors with nodal metastases alone (stages T1 to T3, N1 to 2, M0V0) and a poor prognosis--tumors with venous invasion and/or distant metastases. Histological grading and size of tumor can be used to assess prognosis but are not more accurate than pathological staging. PMID- 2304156 TI - Extracorporeal shock wave lithotripsy in patients with cardiac pacemakers. AB - Between May 1985 and July 1988, 11 patients with cardiac pacemakers were treated for renal or ureteral calculi by extracorporeal shock wave lithotripsy. During treatment and at follow-up no dysfunction of the pacemakers was noted. There were no cardiac complications during extracorporeal shock wave lithotripsy. All 11 patients were free of stones within 3 months after therapy. From these data it can be concluded that in patients with cardiac pacemakers extracorporeal shock wave lithotripsy of renal or ureteral stones can be performed safely when certain precautions are taken and special attention is paid to the electrophysiology of the pacemaker. PMID- 2304157 TI - In situ extracorporeal shock wave lithotripsy for upper ureteral stones using the EDAP LT-01 lithotriptor. AB - We reviewed 64 cases of upper ureteral stones treated between December 1986 and June 1988. Upper ureteral stones were defined as stones in the ureter distal to the ureteropelvic junction and proximal to the S1 vertebra. All stones were treated in situ with no invasive procedures done before treatment. The over-all success rate in rendering patients free of stones by extracorporeal shock wave lithotripsy monotherapy was 75%. Of the patients 25% required auxiliary procedures, such as percutaneous ultrasonic lithotripsy. The average duration of treatment for each stone was 88 minutes and the average storage energy used was 208 units. PMID- 2304158 TI - Clinical experience with a new pulsed dye laser for ureteral stone lithotripsy. AB - We treated 45 patients (46 ureteral stones) with a new pulsed dye laser. A 250 mu. fiber was used through a rigid (40 stones) or flexible (6) ureteroscope. Stones were in the upper (5 cases), middle (5) or lower (36) third of the ureter. Stone composition was calcium oxalate dihydrate (34 patients) or monohydrate (7), struvite (2) or uric acid (2). Of the calculi 36 (78%) were fragmented, including 14 that also required simultaneous basket removal of fragments. Ten stones were not fragmented: 6 because of the pure monohydrate composition and 4 due to malfunction of the laser. No damage to the ureteral wall was noted. Retrograde rigid ureteroscopy with laser lithotripsy was effective for lower and middle third ureteral stones. Flexible ureteroscopy with laser lithotripsy was effective (impacted stones) but difficult for upper third ureteral stones. PMID- 2304159 TI - Paravesical granulomas masquerading as bladder neoplasms: late complications of inguinal hernia repair. AB - Paravesical granuloma formation after inguinal herniorrhaphy is a rare complication due to infected suture material. We present 8 cases of large paravesical granulomas masquerading as bladder tumors. Irritable symptoms predominate the symptom complex and accurate diagnosis can be obtained with multiple, sonographically guided, needle biopsies of the mass. An operation results in complete resolution of the symptoms, while nonoperative management may help to improve but not resolve the symptoms. PMID- 2304160 TI - The ileal neobladder: experience and results of more than 100 consecutive cases. AB - The ileal neobladder produces a completely detubularized, low pressure, high capacity reservoir constructed from ileum without any valves. From April 1986 through May 1989, 113 patients underwent this procedure at our institution. Of these patients 99 underwent simultaneous radical cystectomy for bladder cancer and 14 underwent bladder augmentation. The mean postoperative followup was 14.4 months, with a range of 1 to 36 months. There was no perioperative mortality. However, 7 patients died more than 2 months postoperatively: 5 of tumor progression, 1 of pneumonia and severe metabolic acidosis, and 1 of septicemia of unknown cause. Reoperation was necessary in only 13 patients; 10 patients required urethrotomy or dilation of urethral strictures. Day and night continence was preserved in 82.1% of all patients. Stress incontinence, which must be corrected by an artificial sphincter, was found in 4 patients (4.2%) and night time incontinence that required an external device occurred in 5 (5.3%). Eight patients (8.4%) with mild stress incontinence required no further treatment. Pressure waves exceeding 22 cm. water seldom occurred and then only at maximum capacity. Our experience with this relatively simple system without a nipple is an overwhelming success. The need for reoperation is extraordinarily low and the high reservoir capacity results in continence from the beginning in most patients. The concept is sound and offers a genuine alternative to any form of cutaneous urinary diversion with an incidence of complications not higher than after standard supravesical urinary diversion. PMID- 2304161 TI - Unexpectedly high serum methotrexate levels in cystectomized bladder cancer patients with an ileal conduit treated with intermediate doses of the drug. AB - The pharmacokinetics of serum methotrexate were studied in 45 bladder cancer patients receiving 250 mg. per m.2 as part of the initial cycle of combination chemotherapy. Serum methotrexate was determined routinely 43 to 49 hours after administration. If the methotrexate levels remained at more than 80 nmol. per l. measurements were repeated daily until the serum levels decreased below this point. The patients were classified into group 1-23 with a bladder in situ and no ureteral obstruction, group 2-11 with a bladder in situ and unilateral hydronephrosis, and group 3-11 who had had cystectomy and ileal conduit diversion before chemotherapy. Of the patients in groups 1 and 2, 5 and 6, respectively, had serum methotrexate levels of 80 nmol. per l. or more 43 to 49 hours after administration, which decreased to below this level on the next day. Of the 11 patients in group 3, 8 had elevated methotrexate levels at the initial determination. Daily methotrexate analyses showed a delayed elimination in 4 of 7 patients and levels of more than 80 nmol. per l. for 3 to 9 days. Low creatinine clearance but, in particular, the previous performance of an ileal conduit predicted high methotrexate levels on day 2 after treatment. The most likely explanation for this observation is the resorption of methotrexate by the small bowel mucosa in the ileal conduit. Patients with an ileal conduit performed 2 years or less before chemotherapy and/or those with a long ileal segment seem to have a particularly high risk for delayed methotrexate elimination. Bladder cancer patients with an ileal conduit who receive methotrexate-containing chemotherapy have a high risk of delayed methotrexate elimination and increased clinical methotrexate toxicity. Leukovorin rescue should be used liberally in these patients together with other prophylactic means (intensive hydration and alkalization of the urine). PMID- 2304162 TI - Cavernosography following clinical failure of penile vein ligation for erectile dysfunction. AB - In an attempt to determine what occurs to the venous circulation of the penis after ligation of the deep dorsal vein, 9 men with veno-occlusive dysfunction who underwent deep dorsal penile vein ligation and failed to achieve normal erectile function postoperatively consented to a postoperative cavernosogram. Preoperatively, the deep dorsal vein was visualized in all 9 patients, the cavernous vein in 2 and the corpus spongiosum in 1. Postoperatively, the deep dorsal vein was visualized in 1 patient, the cavernous vein in 1 and the corpus spongiosum in 8. These observations suggest that either the inability to identify a cavernous-spongiosal communication preoperatively or the induction of such a communication postoperatively may lead to a clinical failure in patients who undergo deep dorsal penile vein ligation. PMID- 2304163 TI - Delay in diagnosis and survival in testicular cancer: impact of effective therapy and changes during 18 years. AB - In an effort to determine the impact of a delayed diagnosis in testicular cancer the records of 148 patients with a known interval of delay were reviewed. The over-all mean symptomatic interval of this population was 21.1 weeks and did not change significantly during an 18-year review period. An increased symptomatic interval correlated with an increased presenting stage of disease for nonseminoma and a delay of greater than 16 weeks strongly (p equals 0.002) lowered survival for these patients during the study interval. However, the symptomatic interval was not significantly associated with stage for seminoma patients nor did the symptomatic interval influence survival for these patients. Further analysis of the nonseminoma patients revealed that delay strongly affected survival (p equals 0.001) in the pre-cisplatin era (1970 to 1978) but it was less pronounced (p equals 0.262) in the cisplatin era (1979 to 1987). Despite an attenuation of the effect of delay in the current era of effective chemotherapy, deaths still occur due to delay in diagnosis and programs to lessen delay, such as testicular self examination, and patient and physician education, are strongly encouraged. PMID- 2304164 TI - Testicular seminoma: clinical and pathological features that may predict para aortic lymph node metastases. AB - Patients with clinical stage I testicular seminoma usually receive elective para aortic lymph node radiation after orchiectomy, which is effective in controlling subclinical microscopic disease. However, the majority of patients with clinical stage I seminoma do not harbor occult metastases and, therefore, do not require elective nodal treatment. Vascular space invasion by the primary testis tumor recently has been shown to be an important predictor of metastases in nonseminomatous tumors but no such information exists to date in pure seminoma. Therefore, patients with clinical stage I testicular seminoma were compared to clinical stage II to IV cancer patients with respect to the presence of several features of the primary tumor. Vascular space invasion was identified significantly less frequently in stage I cancer patients (17%, 5 of 29) than in those with stage II or greater disease (39%, 11 of 28, p equals 0.03, 1-tailed t test). Microscopic invasion of the tunica and rete testis, and necrosis also were identified slightly more frequently in the higher stage cancer patients. Of the 12 patients with a maximum tumor dimension of more than 6 cm. 9 (75%) were in the stage II or higher group. Patient age, symptom duration and presenting complaint were similar in the 2 groups. Many higher stage cancer patients did not exhibit aggressive histological characteristics and, therefore, the absence of these features cannot be used to select patients for surveillance. On the other hand, patients with clinical stage I tumors that exhibit vascular space invasion may have an increased rate of occult para-aortic lymph node metastases. Therefore, the presence of vascular space invasion may be a useful criterion for exclusion of patients from surveillance protocols. Confirmatory data are needed before a final recommendation can be made. PMID- 2304166 TI - Nerve-sparing radical prostatectomy: evaluation of results after 250 patients. AB - To examine the efficacy of nerve-sparing radical retropubic prostatectomy in preserving sexual potency and urinary continence, and in providing complete tumor excision we analyzed the records of the first 250 consecutive patients with clinical stage A or B prostate cancer treated since this operation was adopted at our institution. Over-all, sexual potency was preserved in 71 of 112 patients (63%) who underwent bilateral nerve-sparing prostatectomy and 13 of 33 (39%) who underwent a unilateral nerve-sparing procedure with a minimum of 6 months of followup. Preservation of potency correlated with patient age (p equals 0.0035, chi-square) and was significantly (p less than 0.001, chi-square) higher in patients with pathologically organ-confined tumors (72%) than in those with pathologically extracapsular tumors (51%). Of 192 patients followed for at least 6 months 188 (98%) achieved urinary continence postoperatively. Over-all, apparent complete tumor excision as defined by organ-confined tumor with negative surgical margins and undetectable postoperative prostate specific antigen levels was achieved in 14 preoperatively potent patients (42%) who underwent a unilateral and 67 (59%) who underwent a bilateral nerve-sparing procedure. Completeness of tumor excision correlated with tumor stage. In approximately 45% of the patients incomplete tumor excision was owing to seminal vesicle and/or lymph node involvement or positive bladder neck margins that could not be attributed to the nerve-sparing modification. However, improper application of the nerve-sparing technique may have contributed in the others. We were unable to detect microscopic penetration of the capsule or distinguish between gross extracapsular tumor extension and periprostatic fibrosis at operation. We conclude that with proper application of nerve-sparing radical retropubic prostatectomy, potency can be preserved in the majority of patients without compromising the adequacy of tumor excision. The completeness of tumor excision appears to be determined primarily by the extent of the tumor. Therefore, patient selection is important. Patients with focal, well differentiated tumors are ideal candidates for a nerve-sparing procedure, while those with high volume, poorly differentiated tumors may be at a higher risk for positive surgical margins. The benefits of wide excision of the neurovascular bundles remain to be demonstrated formally. PMID- 2304165 TI - Laser-assisted vasectomy reversal: experience in 32 patients. AB - A Food and Drug Administration approved protocol using a microsurgical carbon dioxide laser to assist in vasectomy reversal was instituted in January 1987. Between January 1987 and December 1988 the procedure was performed on 32 patients, 31 of whom submitted sperm and were available to evaluate. Success rates for sperm in the ejaculate in patients who underwent vasectomy less than 10 years previously were excellent, approaching 95%. The pregnancy rate in this group was 35%. In patients whose vasectomy was performed more than 10 years before reversal the results were much poorer. The success rate for sperm in the ejaculate was only 36% and the pregnancy rate was only 9%. The advantage of laser assisted vasectomy reversal is that it is a simpler technical procedure that requires considerably less time than a 2-layer microsurgical technique. There were no significant complications, sperm granuloma, or even significant swelling or hematoma in any patient operated upon. Laser-assisted vasectomy reversal is at least equal to conventional microsurgical techniques and definitely easier to perform surgically. PMID- 2304167 TI - Flexible ureteropyeloscopy in the diagnosis of benign essential hematuria. AB - Benign essential hematuria is an uncommon syndrome that constitutes a dilemma in diagnosis for the urologist. We studied 32 patients with flexible ureteropyeloscopy. Previous studies included renal arteriography, computerized tomography, ultrasound and urinary cytology. The entire intrarenal collecting system was inspected in 28 of the 32 patients and discrete lesions were found in 16. The most common finding was a hemangioma on a renal papilla in 11 patients. A discrete lesion was treated in 12 patients with successful results in 11. Nonspecific abnormalities were found in 9 patients and attempts at treatment of these lesions in 4 were unsuccessful. No lesion was found in 5 patients. Flexible ureteropyeloscopy offers a minimally invasive approach for the diagnosis of unilateral gross hematuria. Treatment of solitary small discrete lesions was highly successful. PMID- 2304168 TI - Endoscopic diagnosis and treatment of chronic unilateral hematuria of uncertain etiology. AB - We evaluated 12 patients with unilateral unexplained gross hematuria by flexible ureteropyeloscopy and percutaneous pyeloscopy. All patients had localized bleeding except for 1 with diffuse bleeding caused by the nutcracker phenomenon, and 2 in whom no hematuria appeared upon examination and no gross lesions were observed. Among the 9 patients with localized bleeding transitional cell carcinoma was found in 1, hemangioma in 4 and minute venous rupture in 4. These 9 patients were treated endoscopically and no recurrences were observed during a follow-up of 6 to 21 months (average 10.3 months). Our results underscore the importance and efficacy of flexible ureteropyeloscopy in the evaluation and management of chronic unilateral hematuria. PMID- 2304169 TI - Safe and effective, prolonged administration of epsilon aminocaproic acid in bleeding from the urinary tract. AB - A total of 9 patients with macroscopic hematuria from various causes, none with evidence of disseminated intravascular coagulation, received low oral, divided doses (approximately 150 mg. per kg. per day) of epsilon aminocaproic acid for up to 21 consecutive days. The hematuria was controlled effectively without overt clinical reactions. Parameters of hepatic and renal function, indicators of muscular damage, were studied in detail in 3 patients. No significant abnormalities were found. The use of small doses of epsilon aminocaproic acid was not accompanied by significant complications and appeared to be effective in special situations for the control of urinary bleeding. This therapy may have indications in a number of urological states accompanied by excessive hematuria. PMID- 2304170 TI - Diagnostic artificial erection without corpus cavernosum injection. AB - The vacuum erection device can be used to produce an artificial erection for documentation of penile curvature. This technique is illustrated in the preoperative evaluation of a patient with Peyronie's disease. PMID- 2304171 TI - The anatomy of stress incontinence: magnetic resonance imaging of the female bladder neck and urethra. AB - Clinical, urodynamic, radiological and endoscopic evaluations as well as operative results on more than 800 cases of stress incontinence treated at our medical center have led to a better understanding of the pathophysiology of female stress incontinence. We attempt to correlate these physiological concepts with information obtained from magnetic resonance images of the paraurethral and bladder neck areas in patients with known stress incontinence and normal controls. All magnetic resonance images were compared to cadaver step sections of the female pelvis. Normal controls without stress incontinence were used to define normal anatomy by magnetic resonance imaging. Etiology of incontinence was divided into either intrinsic urethral damage or anatomical malposition of an intact sphincteric unit. Our findings not only provide valuable support to basic concepts of the pathophysiology of stress incontinence but also help to establish normal findings of female paraurethral and bladder neck anatomy as seen by magnetic resonance imaging. PMID- 2304172 TI - Neonatal adrenal hemorrhage presenting as scrotal hematoma. AB - A neonate with hemorrhage of the right adrenal gland who presented with bilateral scrotal masses is described. The difficulty in establishing the diagnosis and ruling out testicular torsion is outlined. The differential diagnosis of scrotal swelling is listed. Adrenal hemorrhage can produce hemoperitoneum but this case is unique in that hemoperitoneum was not associated with signs of peripheral circulatory insufficiency and/or abdominal distension, and was manifested only by bilateral scrotal hematomas. The implication of these findings is emphasized. PMID- 2304173 TI - Right renal mass with vena caval thrombus. AB - This case illustrates the difficulties that sometimes occur in the evaluation of patients with a nonfunctioning kidney. Because of the clinical presentation, suggestive of renal cell carcinoma, no urinary cytology study was obtained from the affected kidney. This study certainly would have led to the correct diagnosis. Despite this fact, the operative management would not have changed except for complete removal of the ureter. In our case we elected to follow the distal ureter by ureteral washings and ureteroscopy during follow-up cystoscopy studies to preclude a further operation. Although no data are available on the role of adjuvant therapy in these patients, because of the poor prognosis associated with such extensive disease we gave our patient 2 courses of M-VAC in an attempt to prevent progression of the disease. PMID- 2304174 TI - Post-nephrolithotomy chyluria. AB - Percutaneous nephrolithotomy has proved to be a cost-effective, safe and expeditious means of renal calculus removal since its introduction in the late 1970s. The inherent risks and complications of this procedure have been well documented but less common complications continue to surface as case selection becomes increasingly more difficult. We report a case of chyluria after percutaneous nephrolithotomy. The patient recovered completely after treatment with total parenteral nutrition and required no further intervention. The etiology as well as the treatment of this previously unreported complication following percutaneous nephrolithotomy is addressed. PMID- 2304175 TI - Caliceal-cutaneous fistula in renal transplantation: successful conservative management. AB - Caliceal-cutaneous fistula is an uncommon complication of renal transplantation that frequently leads to graft resection. We report our experience with the successful conservative management of a case of caliceal-cutaneous fistula secondary to acute allograft rejection in a renal transplant recipient. PMID- 2304176 TI - Ureteroarterial fistula: case report and review of literature. AB - A fistula developed between the left common iliac artery and the distal left ureter of an 83-year-old woman who had undergone aortofemoral bypass grafting many years previously and in whom a Double-J stent was in place for 3 weeks while she was awaiting extracorporeal shock wave lithotripsy. Exsanguinating hemorrhage into the urinary tract necessitated emergency nephrectomy and vascular repair. Although these measures were successful temporarily, the patient died 6 weeks later of repeat myocardial infarction and acute renal failure. The increasing frequency of ureteral stent use and of an operation on the iliac arteries is expected to increase the frequency of these potentially catastrophic fistulas. PMID- 2304177 TI - Priapism associated with intranasal cocaine abuse. AB - Cocaine abuse has escalated to epidemic proportions in the United States. In addition to the social and economic problems associated with the recreational use of this agent, a variety of medical complications have been reported. The occurrence of priapism with intranasal use has not been documented previously. We report a case of priapism secondary to intranasal cocaine abuse and describe the possible neurochemical etiology for this phenomenon. PMID- 2304178 TI - Re: Indomethacin as prophylaxis against ureteral colic following extracorporeal shock wave lithotripsy. PMID- 2304179 TI - Re: Risk factors for perineal seeding of prostate cancer after needle biopsy. PMID- 2304180 TI - The effect of acute obstruction on ureteral function. AB - In an effort to understand the physiologic processes which contribute to, or hinder the transport of stones through the ureter, we examined the intraluminal ureteral pressures and peristaltic activity above and below the acutely obstructed site. Because of patient differences, variability in stone size, shape and composition, an in vivo animal model was developed to study acute ureteral obstruction. Five adult mongrel dogs were anesthetized. A midline celiotomy was made and an open-ended ureteral catheter was inserted through a distal ureterotomy and advanced up the ureter. An angiographic balloon catheter was inserted through a small nephrotomy and directed down the ureter. The experiment was divided into phases: control, ureteral obstruction (balloon inflation) and release of obstruction (balloon deflation). Compared to control values, peristaltic rate above the obstruction increased significantly (p less than 0.05), as well as baseline, peak, and delta (peak minus baseline) pressures. In contrast, the peristaltic rate below the obstructed site remained approximately the same as its control, despite the significant decreases in baseline, peak, and delta (p less than 0.05) pressures. Failure of transmission of effective peristalsis across the obstructed site may hinder stone passage; however, this remains to be proven. Moreover, the failure of transmission of the increased rate of peristalsis past the balloon and persistence of peristaltic activity below the site of obstruction despite absence of urine flow suggest segmental forces influence peristaltic activity. PMID- 2304181 TI - Tapered intraluminal versus imbricated extraluminal valve: comparison of two continence mechanisms for urinary diversion. AB - One of the major limitations of continent intestinal reservoirs currently in use is failure of the efferent continence mechanisms. Unsatisfactory results have been reported in the literature in up to 40% of cases. While progress has been made toward better continence in urinary diversions, evolution of the actual continence mechanisms has been along two rather distinct paths: those with a valve mechanism placed inside the pouch (either by intussusception or surgical insertion), and those with the valve outside to the pouch (by imbrication of an externally located ileal segment). A canine experimental model was used to investigate a type of intraluminal continence mechanism and to compare it to an extraluminal imbricated ileocecal valve. In eight mongrel dogs a reservoir was made out of ascending and transverse colon with two different valve mechanisms- one intraluminal and one extraluminal--connected via separate stomas to the skin. Radiographic, sonographic, endoscopic and urodynamic studies of the pouch and its outlets were performed. Results showed that, in contrast to the extraluminal valve, continence in the intraluminal valve was volume dependent. The valve closing pressure of the intraluminal continence mechanism increased far beyond the values of the extraluminal valve (50.38 vs. 30.12 cm. H2O) at maximum pouch filling. Leakage of the intraluminal valve was observed at significantly higher pouch volumes than in the extraluminal valve (348 cc vs. 215 cc). In view of these results, the volume dependent intraluminal valve mechanism appears superior to an extraluminal type, especially at higher pouch volumes. PMID- 2304182 TI - Stimulation of urinary bladder tumorigenesis by carcinogen-exposed stroma. AB - There is evidence to suggest that control mechanisms, either growth-stimulatory, inhibitory or inductive, may play a role in carcinogenesis. To test the hypothesis that treatment of rat urinary bladder with carcinogen induces alterations in the stroma which result in modified epithelial-stromal interactions, experiments were conducted using a rat model specifically designed for the study. Following exposure of Fischer F344 rats in drinking water to the urinary bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) for four weeks, bladders were removed and subjected to a brief detergent treatment to completely remove epithelium. The bladders without epithelium ("stroma" bladder) were heterotopically transplanted to syngeneic recipients. Four days later, the denuded mucosa surface was resurfaced with intraluminal instillation of urothelial cells, either untreated or treated with BHBN for six weeks (6w-BHBN) or 10 weeks (10w-BHBN). Examination at 12 weeks posttransplant of the "stroma" bladders that had received 6w-BHBN urothelial cells showed a higher tumor incidence of carcinoma in the BHBN-exposed "stroma" bladders as compared with the incidence in the carcinogen-unexposed "stroma" bladders (p less than 0.05). Examination at 18 weeks posttransplant showed 100% incidence of tumors in all "stroma" bladders irrespective of the lengths of BHBN exposure of urothelial cells. However, among the bladders that had received 6w-BHBN urothelial cells, carcinogen-exposed "stroma" bladders proved to be better "soil" for neoplastic cells to proliferate; the mean tumor volume as well as the mean total tumor volume per bladder were significantly higher than in the control "stroma" bladders (p less than 0.01 for each comparison). Similarly, among the bladders that had been resurfaced with 10w-BHBN urothelial cells, the mean total tumor volume per bladder was greater in the carcinogen-treated "stroma" bladders than in the controls (p less than 0.05). No proliferative or neoplastic changes were observed in the BHBN exposed "stroma" bladders which had been resurfaced with normal urothelial cells. Our data indicate that neoplastic growth of carcinogen treated urothelium is enhanced when such cells interact with the stroma which has also been exposed to carcinogen. PMID- 2304183 TI - Molecular analysis of the short arm of chromosome 3 in five renal oncocytomas. AB - Renal oncocytomas were tested for loss of alleles at loci on the short arm of chromosome 3, a genetic change characteristic of human renal cell carcinoma. Five renal oncocytomas did not show loss of alleles at loci on 3p supporting the view that renal oncocytoma is a distinct form of renal neoplasia. PMID- 2304184 TI - Ablation of the inferior mesenteric plexus in the rat: alteration of sperm storage in the epididymis and vas deferens. AB - The involvement of the sympathetic nervous system in the transport and storage of spermatozoa in the male reproductive tract was examined by surgically ablating the inferior mesenteric plexus (IMP). One to eight weeks after ablation of the IMP, epididymal weight and the total number of spermatozoa present in the cauda epididymidis were significantly greater in IMP-ablated rats than in sham-operated rats. By contrast, the number of spermatozoa present in the initial segment of the vas deferens was significantly greater than in sham operated controls one week after IMP ablation but returned to control levels at two, four, six and eight weeks. Throughout the experiment, no differences were observed between IMP ablated and control rats in the percentage of motile cauda epididymal spermatozoa, testicular weight, testicular sperm number or serum testosterone. These data demonstrate that the sympathetic nervous system differentially regulates sperm transport and storage in the male reproductive tract and suggest that the IMP may influence the epididymal maturation of spermatozoa. PMID- 2304185 TI - Hemodynamic effect of the metallopurpurin SnET2 and light on transplantable FANFT induced bladder tumor. AB - Changes in blood flow to transplantable N-[4-(5-nitro-2-furyl)-2 thiazolyl]formamide induced bladder tumors growing subcutaneously in the flanks of Fischer CDF (F344/CrlBR) rats were measured after photodynamic therapy with the photosensitizer tin (II) etiopurpurin dichloride using the radioactive microsphere technique. As with the other photosensitizers, hematoporphyrin derivative and chloroaluminum tetrasulfophtalocyanine, tin (II) etiopurpurin dichloride and light caused a rapid decrease in tumor blood flow in this tumor model. The decrease in blood flow occurred whether the vehicle for photosensitizer delivery was an emulsion or a liposome. Systemic heparinization of animals prior to light treatment did not alter changes in tumor blood flow. PMID- 2304187 TI - The elasticity and the tensile strength of tunica albuginea of the corpora cavernosa. AB - The aim of this study was to determine the tensile strength and the elasticity of the tunica albuginea (TA), and describe morphological structures in the tissue before and after mechanical deformities. Twenty cadavers of men aged between 33 and 83 were examined. Cavernosometry was performed in all specimens. Afterwards in five cadavers the flow rate was increased until a herniation of the TA appeared. A strength about 1500 mm. Hg was found. Similar results were found in four who had an inflatable prosthesis (AMS 700) inserted, and the intraprosthetic pressure increased until a deformity was noted. Slices of TA (thickness 1.3 to 3.3 mm.) from 11 specimens were tested in a tensiometer. The elasticity coefficient was found to be around 10(8) N/m2, and the tensile strength to be 600 to 750 mm. Hg (10(4) to 10(5) N/m2). The difference between the tensile strength achieved in the tensiometer and during saline infusion is possibly caused by the intracavernous framework. Microscopy showed that TA is mainly composed of collagen fibres which are situated in an undulating arrangement, with a few elastic fibres arranged longitudinally which connect the undulating bundles of collagen fibres. When the tissue is overstretched, the elastic fibres are destroyed and the undulating arrangement disappears. PMID- 2304186 TI - The effects of testicular trauma on fertility in the Lewis rat and comparisons to isoimmunized recipients of syngeneic sperm. AB - Adult male Lewis (LEW) rats were used to investigate the effects of unilateral testicular trauma on fertility. Comparisons were made between normal and experimental rats immunized with syngeneic sperm in Complete Freund's Adjuvant (CFA). Matings within the three groups yielded offspring to all normal males, no offspring to the immunized rats, and 27% (3/11) fertility in the trauma group (p less than 0.001). The contralateral testis demonstrated decreased volumes, various degrees of aspermatogenesis and smaller seminiferous tubular diameters, in both the trauma and immunized groups compared to the controls. Similar histopathologic findings of chronic granulomatous inflammation within contralateral testes in both the trauma and immunized groups suggested a common immune etiology for infertility via possible disruption of the blood-testis barrier. PMID- 2304188 TI - Investigative grammar. PMID- 2304190 TI - Brain cholinesterase inhibition in songbirds from pecan groves sprayed with phosalone and disulfoton. AB - Brain cholinesterase (ChE) activities of songbirds collected in pecan groves 6 to 7 hr after separate applications of the organophosphorus pesticides, phosalone and disulfoton, were compared to mean ChE activities of controls (normals) as a measure of insecticide exposure. In general, reduction of brain ChE activity greater than or equal to 2 standard deviations below the control mean indicates exposure to an anticholinesterase compound. Phosalone had little effect on brain ChE activity of birds from treated groves; only slight to moderate (21 to 38%) ChE inhibition was detected in blue jays (Cyanocitta cristata) and red-bellied woodpeckers (Melanerpes carolinus). However, 11 of 15 blue jays from disulfoton treated groves had moderate to severe ChE depression, ranging from 32 to 72%. Inhibition greater than or equal to 50% of normal may be diagnostic for cause of death. Direct mortality was not observed, but studies have shown that bird carcasses disappear rapidly from agricultural areas, many within 24 hr. We recommend additional field studies of the effects of disulfoton to wildlife, since large wheat-growing areas in the western United States are being considered for disulfoton treatment to control the Russian wheat aphid (Diuraphis noxia). PMID- 2304189 TI - Bird-feeding ticks transstadially transmit Borrelia burgdorferi that infect Syrian hamsters. AB - Bird-feeding Ixodes dammini ticks were documented for the first time to successfully molt and transstadially pass Borrelia burgdorferi spirochetes that were indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from the type B31 strain. Forty-six of 73 blood-engorged larvae and 50 of 66 fully-fed nymphs, removed from wild-caught birds, successfully molted. Borreliae were isolated from 21 of 78 partially- and fully-fed larvae off birds, including six specimens that molted. Spirochete-positive cultures also were obtained from 35 of 60 partially- and fully-fed nymphs that had fed from birds, including 20 nymphs that molted into adult ticks. Transstadially passed borreliae by bird-feeding larval and nymphal I. dammini were infectious to hamsters, leading us to suggest that these ticks are capable of subsequently transmitting infectious spirochetes to mammals, including humans. An isolated of B. burgdorferi, recovered from a bird-feeding larval Ixodes dentatus, was indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from the B31 strain. This isolate, unlike another from I. dentatus off a cottontail rabbit (Sylvilagus floridanus), had a protein band with a molecular weight of approximately 31,000 that reacted with murine monoclonal antibodies H3TS and H5332 in western blot analysis. Thus, closely related borreliae are present in both I. dentatus and I. dammini. PMID- 2304191 TI - Isolation of Brucella melitensis biovar 3 from a chamois (Rupicapra rupicapra) in the southern French Alps. AB - Systemic brucellosis caused by Brucella melitensis biovar 3 was identified in a chamois (Rupicapra rupicapra) near the Parc National des Ecrins in the southern French Alps (France). Clinical signs included orchiepididymitis, polyarthritis, blindness and various neurological signs; necropsy findings included numerous calcified foci in testis, epididymis, kidney, subcutaneous connective tissue and brain. Brucella sp. were identified in brain by indirect immunofluorescence and B. melitensis biovar 3 was isolated from testis, kidney, eye, lung and joints. This report describes the first case of brucellosis and Brucella sp. isolation in chamois in France and the first case of B. melitensis isolation in this host species. PMID- 2304192 TI - Salmonellae in the African great cane rat (Thryonomys swinderianus). AB - Because of its large size, the African great cane rat (Thryonomys swinderianus) is valued for food and has become a popular meat in western Africa. A survey was conducted to determine the occurrence of salmonellae in cane rats. Ten strains of Salmonella sp. were isolated from eight of 25 (32%) cane rats. Salmonella ajiobo was isolated from the spleen and intestines of three cane rats; S. agama was obtained from the spleen, liver and intestines of three animals; and S. poona was isolated from the spleen and liver of two cane rats. The occurrence of salmonellae in T. swinderianus is a potential public health hazard. Humans may become exposed to infection by consumption of inadequately cooked infected cane rat meat, or by eating vegetables, sugar cane and fruits contaminated with excretions of carrier cane rats. Incidents of human salmonellosis attributable to cane rat meat have not yet been reported; however, all three serotypes isolated from the cane rats have also been isolated from stools of patients suffering from gastroenteritis in Nigeria. PMID- 2304193 TI - Multiple feather follicle cysts in a wild turkey. AB - A hunter-killed wild turkey (Meleagris gallopavo silvestris) was submitted for examination because of numerous 2 to 30 mm diameter, yellowish, hard nodules in the skin. The nodules were confined to the skin and did not involve subcutaneous tissues. Nodules consisted of dilated feather follicles packed with a caseous tan to pale yellow material. Histologically, affected feather follicles were markedly dilated and filled with laminated keratin debris. The lesions were determined to be multiple feather follicle cysts of unknown etiology. PMID- 2304194 TI - Fractured mandible and associated oral lesions in a subsistence-harvested bowhead whale (Balaena mysticetus). AB - A fractured right mandible with midlength nonunion and oral lesions were noted in a subsistence-harvested female bowhead whale (Balaena mysticetus) near Wainwright, Alaska (USA). The cause of the fracture was not apparent. The fracture resulted in misalignment of the mandible. The abnormal mobility at the fracture site probably caused irregular baleen stowage within the oral cavity, leading to breakage of many baleen plates and extensive ulceration of the tongue and lips. Good body condition suggested the fracture was not debilitating. PMID- 2304195 TI - Epidemic oral ulceration in largemouth bass (Micropterus salmoides) associated with the leech Myzobdella lugubris. AB - An epidemic of severe ulcerations of the tongue and buccal cavity was documented in subadult and adult largemouth bass (Micropterus salmoides) from Currituck Sound, North Carolina (USA). Other external clinical signs were not present. Between November 1986 and May 1987, reports from fishermen indicated that as many as 90% of large (greater than 300 mm total length) bass were affected. Older fish were the most commonly involved. The leech, Myzobdella lugubris (= Illinobdella moorei), was consistently present on or near the lesions. Lesions were heavily infected with several different bacteria that were apparently secondary invaders. Stressful (high) salinity or an interruption in the normal migratory cycle of the parasite are suggested as possible causes for this condition in these bass. PMID- 2304196 TI - Parasites from the Asiatic black bear (Ursus thibetanus) on Kyushu Island, Japan. AB - Two Dirofilaria ursi, six Trichodectes pinguis and numerous Haemaphysalis megaspinosa were obtained from an Asiatic black bear (Ursus thibetanus) shot in Kyushu, Japan. The presence of two parasites specific to black bears may indicate the existence of a wild population, although the bears are regarded to be extinct on Kyushu Island. PMID- 2304197 TI - Helminth parasites of unisexual and bisexual whiptail lizards (Teiidae) in North America. I. The Colorado checkered whiptail (Cnemidophorus tesselatus). AB - Eleven of 27 (41%) parthenogenetic Colorado checkered whiptails (Cnemidophorus tesselatus) from four counties of western and southwestern Texas were infected with one or more helminths. These included a linstowiid cestode (Oochoristica sp.), a larval spirurid nematode (Physaloptera sp.) and two species of oxyurid nematodes (Parathelandros texanus and Pharyngodon warneri). This note, the first in a series of reports on helminths of Cnemidophorus spp., represents the first record of parasites from C. tesselatus. PMID- 2304198 TI - Raptors rehabilitated in Iowa during 1986 and 1987: a retrospective study. AB - A retrospective study was conducted on 60 raptors representing 13 species treated at the Iowa State University College of Veterinary Medicine during 1986-1987. Eight species (31 individuals) were Falconiformes and five species (29 individuals) were Strigiformes. Seventy-five percent of all injuries were due to trauma and 65% of these were injuries arising from human activity, including car collisions (28%), shooting (17%) and trapping (11%). Thirty-four percent of all raptors admitted were treated and released, 25% were permanently crippled and 41% died during treatment or were euthanized. Data from this study implicate trauma resulting from human activity as a major reason for injury in free-ranging raptors presented for treatment in Iowa. PMID- 2304199 TI - Experimental avian PMV-2 infection in a domesticated wild host: daily behavior and effect on activity levels. AB - Paramyxovirus type 2 (PMV-2) isolated from wild birds is often considered non pathogenic, but nothing is known about its effects on overall behavior and fitness of free-flying birds. Domestically bred, African cut-throat finches (Amadina fasciata), a species from which PMV-2 has been isolated in the wild, were inoculated with a Central American field strain of PMV-2. Patterns of behavior were examined before and after viral challenge to quantify inapparent, sublethal effects of the disease. Infected birds demonstrated a significant decrease in activity (P = 0.01) followed by an apparent recovery period. Antibody titers confirmed infection in inoculated birds and indicated that sentinel birds did not become infected. PMID- 2304200 TI - Effect of diet on condition indices in black-tailed jackrabbits. AB - Changes in blood, urine and physical condition indices in 23 adult male black tailed jackrabbits (Lepus californicus) with ad libitum feeding and 25% feed restriction were measured over a 2 wk period from 30 May to 12 June 1988. Feed restricted jackrabbits had (1) lower post-trial body weights and kidney fat indices, (2) higher femur marrow fat, serum bilirubin and cortisol concentrations, and adrenal cortex width, and (3) depressed immune function. No single index alone could best measure the nutritional status of these jackrabbits. PMID- 2304201 TI - Invasive entamoebae in pronghorn (Antilocapra americana) from Wyoming. AB - Trophozoites and cysts of an amoeba resembling Entamoeba bovis were recovered from soft stools of captive pronghorn fawns (Antilocapra americana). Chronic or intermittent diarrhea was observed in most individuals in two groups of hand raised 1- to 8-mo-old pronghorns. Ileocecal lymph nodes were mildly to moderately enlarged. Microscopic lesions were characterized by lymphoid hyperplasia, focal necrosis and pyogranulomatous inflammation in lymph nodes and focal necrosis and diffuse nonsuppurative enteritis in ileum and cecum. In 12 of 17 fawns, trophic stages of amoebae were observed in the submucosa of the cecum and/or the cortex of the ileocecal lymph node. This is the first report of E. bovis-like organisms invading and causing pathological changes in the tissues of their host. PMID- 2304202 TI - Changes in mallard (Anas platyrhynchos) serum chemistry due to age, sex, and reproductive condition. AB - Selected serum constituents were analyzed from 50 adult mallards (Anas platyrhynchos) of both sexes during several stages of reproduction: pre-egg laying, egg laying, incubating, molting, and postreproductive. Similar assays were conducted on sera from ducklings aged 5 to 58 days. Values for total protein (TPR), albumin (ALB), glucose (GLU), gamma-glutamyl transferase (GGT), calcium (CA), phosphorus (PHOS) and magnesium (MG) differed by sex. When all data were combined and analyzed for sex-related differences within each reproductive condition separately, all assays except lactate dehydrogenase (LD-L), cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRN) and direct bilirubin (BIDI) differed between sexes during one or more reproductive periods. Each assay showed differences among the various reproductive conditions regardless of gender. The pattern of change differed between sexes. All assays except ALB, GLU, CA and MG showed age-related changes. Lipemia in the sample interfered with all chemistries except TPR, LD-L and CA. Results indicate that when using clinical chemistry as a diagnostic tool in the mallard, age and reproductive condition should be determined in order to compare the data to appropriate control values. PMID- 2304203 TI - Differential white blood cell values of the mallard (Anas platyrhynchos) across different ages and reproductive states. AB - Differential white blood cell counts were recorded for adult mallards (Anas platyrhynchos) of both sexes during several stages of reproduction: pre-egg laying, egg laying, incubating, molting, and postreproductive. Similar counts were made for young birds from 5 to 60 days of age. No significant (P less than or equal to 0.05) differences amongst the cell ratios due to sex or reproductive state of the adult birds were noted. Nonlaying and laying birds had similar numbers of thrombocytes which were significantly greater than thrombocyte numbers of incubating, molting or postreproductive birds. Young birds had a decrease in the percent lymphocytes from 50 to greater than 60 days of age and a concomitant, compensating increase in percent heterophils. Thrombocyte numbers increased from 5 days of age to a peak at 18 days of age, after which they did not vary significantly. PMID- 2304204 TI - Blood and urinary profiles of free-ranging desert mule deer in Arizona. AB - As a corollary to a more comprehensive study on their ecology, we documented blood and urinary profiles for 10 free-ranging desert mule deer (Odocoileus hemionus crooki) (five males, five females) captured by net-gun shot from a helicopter during February 1988 in Saguaro National Monument, Arizona. Pursuit with the helicopter for netting deer ranged from 3 to 15 min. Blood profiles included seven hematological characteristics and 12 serum chemistries, electrolytes, hormones and enzymes. Urine samples were assayed for urea nitrogen, creatinine, sodium, potassium, calcium and phosphorus. Urinary data were compared as ratios to creatinine. Serum cholesterol was greater (P less than 0.05) in males than females. Pursuit time was correlated with serum non-esterified fatty acids (r = 0.67, P less than 0.05) and influenced urinary specific gravity (r2 = 0.77, P less than 0.004), urea nitrogen: creatinine (r2 = 0.79, P less than 0.005), and potassium: creatinine (r2 = 0.42, P = 0.08) ratios. Increasing specific gravity was related to urinary creatinine concentration (r2 = 0.72, P less than 0.008). All deer exhibited acute adrenal stimulation, accompanied by elevated serum creatine phosphokinase and urinary potassium: creatinine ratios, which were indicative of acute excitement and muscle trauma associated with the capture process. We demonstrated that urinary data are a valuable supplement to serum data in demonstrating effects of intense physical exertion, and both forms of data emphasize the need to assess capture-related excitability as a source of variation in blood and urine characteristics of free-ranging desert mule deer. PMID- 2304205 TI - Physiological and behavioral responses of gray wolves (Canis lupus) to immobilization with tiletamine and zolazepam. AB - We conducted a series of experiments to examine the efficacy of Telazol (TEL) for immobilization of captive gray wolves (Canis lupus). Ten wolves were immobilized with either 5 or 10 mg/kg TEL. There was no difference in induction time (6.5 +/- 0.8 versus 5.8 +/- 1.2 min; P = 0.63) between the two doses, but the time to initial arousal was longer for the higher dose (P = 0.0008). Wolves were again immobilized with 10 mg/kg TEL and upon initial arousal were given additional doses of either 5.0 mg/kg TEL or 2.5 mg/kg ketamine (KET) to maintain immobilization. Wolves given boosters of TEL had longer second recovery times than wolves given KET (P = 0.01). There were no differences in induction times or arousal times for wolves immobilized with TEL that had been reconstituted with sterile water and stored at 20 C for 30 days (P greater than or equal to 0.11) or 60 days (P greater than or equal to 0.27) when compared to immobilization times using fresh solution. Induction times for wolves given TEL reconstituted with water and propylene glycol and stored for 60 days at -9 C were longer (P less than 0.05) than such times for wolves given standard TEL, but time to initial arousal was unchanged (P greater than or equal to 0.44). There were no differences in heart rates (P = 0.36), blood pressures (P = 0.32), respiratory rates (P = 0.91), and rectal temperatures (P = 0.62) between the two TEL doses. Telazol was shown to be an effective and safe immobilizing agent for gray wolves. PMID- 2304206 TI - Chemical immobilization of red foxes (Vulpes vulpes). AB - Red foxes (Vulpes vulpes) were immobilized with one of the following drug combinations: ketamine/xylazine (n = 22), ketamine/promazine (n = 35), ketamine/midazolam (n = 13), or tiletamine/zolazepam (n = 22). Foxes given ketamine/xylazine had the shortest induction and longest recovery times relative to other drug combinations, whereas foxes given ketamine/midazolam had the longest induction times. Recommended doses for the various combinations are given. Foxes given ketamine/xylazine were given either 0.1, 0.2, 0.4 mg/kg yohimbine, or saline 40 min after anesthetic induction. Administration of yohimbine significantly shortened arousal and recovery times relative to control values (P less than 0.001). PMID- 2304208 TI - Guarding the guardians: research on editorial peer review. Selected proceedings from the First International Congress on Peer Review in Biomedical Publication. May 10-12, 1989, Chicago, Ill. PMID- 2304207 TI - Ineffectiveness and comparative pathogenicity of attenuated rabies virus vaccines for the striped skunk (Mephitis mephitis). AB - Three attenuated rabies virus vaccines (SAD-B19, ERA/BHK-21, AZA 2) were compared for efficacy and safety in the striped skunk (Mephitis mephitis) by the oral and intranasal routes. The SAD-B19 and ERA/BHK-21 vaccines were given orally; all three vaccines were given intranasally. Oral administration of SAD-B19 and ERA/BHK-21 vaccines induced neither seroconversion nor significant protection against rabies challenge. One skunk which consumed a SAD-B19 vaccine-laden bait succumbed to vaccine-induced rabies. Intranasal instillation of the three vaccines resulted in the deaths of two of six (AZA 2), three of six (ERA/BHK-21) and six of six (SAD-B19) skunks. PMID- 2304209 TI - The communities of scientists and journal peer review. PMID- 2304210 TI - Who are the peer reviewers and how much do they review? AB - To assess the nature and work load of reviewers for the American Journal of Public Health, I surveyed a sample of 276 reviewers in the latter half of 1988, with a 96% response rate. Respondents reported reviewing papers for 274 other journals in 1987, 81% of which were monitored by the Science Citation Index or the Social Science Citation Index. They reviewed most often for The Journal of the American Medical Association (27%), the American Journal of Epidemiology (26%), and the New England Journal of Medicine (23%). The median number of journals for which they reviewed was 3.6, the median of their estimated review time was 2.7 hours, and the weighted average review time (adjusted for number of reviews) was 2.4 hours. The range of review time was broad and inversely related to the number of papers reviewed. Respondents donated an estimated 3360 hours of uncompensated labor to the American Journal of Public Health in 1987, and a total of 6439 hours (26.8 hours per reviewer) to reviewing for all journals. Of the reviewers for the American Journal of Public Health, only 31% were not listed as an author of a source publication in the 1987 Science Citation Index and only 15% were not cited. PMID- 2304211 TI - What do peer reviewers do? AB - We conducted a prospective 9-month survey to assess the refereeing work load of British Medical Journal referees, and, in particular, to compare the work loads of pediatricians and psychiatrists. Referees completed a record form for each manuscript reviewed and a questionnaire on demographic characteristics and attitudes toward refereeing. Two hundred eleven referees formed a sample of one sixth of the British Medical Journal's active referees; all remaining pediatricians (n = 67) and psychiatrists (n = 65) formed two further samples. Of the 343 referees selected, 301 returned forms or questionnaires. One hundred forty-six referees were editors or on editorial boards. They reviewed for a mean of five journals. They reviewed 1980 manuscripts (a median of 6 for the main sample, 6.5 for the pediatricians, and 8 for the psychiatrists). Most manuscripts were reviewed for journals in the referee's own specialty; only one third were reviewed for other journals. Psychiatrists did significantly more work for general journals than pediatricians (13% vs 9%). All three groups spent less than 2 hours per manuscript. PMID- 2304212 TI - Variation in journal peer review systems. Possible causes and consequences. AB - To investigate disciplinary differences in how scientific journals evaluate submissions, I collected data from the Astrophysical Journal, Physiological Zoology, and the American Sociological Review. Referees' evaluations of submissions to these journals differed strikingly: nearly half of the referee reports for American Sociological Review recommended outright rejection, while the corresponding proportions for the other two journals were about one fourth and one tenth. Final dispositions show even greater variation, with Astrophysical Journal accepting 91% of submissions, Physiological Zoology 59%, and American Sociological Review 13%. The journals also differed substantially in the average number of revisions of eventually accepted papers and the average time lags between submission and final editorial decisions. Such differences conform to claims that disciplinary differences in consensus on research priorities and procedures contribute to variation in typical journal peer review systems. Review systems, in turn, influence authors' experiences in the peer review process. PMID- 2304213 TI - Quotational and reference accuracy in surgical journals. A continuing peer review problem. AB - Fifty randomly selected references from a single monthly issue of The American Journal of Surgery; Surgery, Gynecology and Obstetrics; and Surgery were evaluated for citation and quotation errors. Thirteen major and 41 minor citation errors were found in the three journals. Thirty-seven major quotation errors were identified. The data support the hypothesis that authors do not check their references or may not even read them. This hypothesis may be expanded to maintain that reviewers do not check references. PMID- 2304214 TI - An exploratory study of statistical assessment of papers published in the British Medical Journal. AB - Statistical assessment of papers submitted to the British Medical Journal has increased to some 300 papers annually. The assessment produces a recommendation to the editor on each paper from a statistical viewpoint together with a completed checklist that indicates the quality of certain important features. This exploratory study was aimed at monitoring the process. It reports a comparison of checklist answers on 45 papers as originally submitted with those on the papers as subsequently published. Of the 45 papers, only 5 (11%) were considered statistically acceptable at submission, but this increased to 38 (84%) after publication. Revisions had not been made adequately in 4 of the 7 unsatisfactory published papers, and the 3 others were thought to be of dubious validity. A major omission from at least 28 papers was information on sample size calculations. It is concluded that statistical assessment is beneficial but that further efforts by authors and assessors could make it even more effective. PMID- 2304215 TI - Problems identified by secondary review of accepted manuscripts. AB - To test the hypothesis that no important deficits would be identified on further review of accepted manuscripts, and that such manuscripts would be recommended for publication on rereview, we sent manuscripts that had been accepted for publication, after review and revision, for rereview by new referees who were unaware of the status of the manuscripts. Each review was evaluated independently by two assistant editors to determine whether substantive criticisms were identified by the new reviewers. The majority of manuscripts were thought by the new reviewers to have defects that warranted further revision, but the problems noted were often dissimilar. However, 80% of the manuscripts were recommended for publication and others were judged suitable for publication, although not at a high priority. The assistant editors frequently differed in their judgments whether a given criticism of a reviewer warranted further revision; nevertheless, there was infrequent disagreement regarding the basic decision for acceptance or rejection. PMID- 2304216 TI - The effects of blinding on the quality of peer review. A randomized trial. AB - Peer reviewers are blinded sometimes to authors' and institutions' names, but the effects of blinding on review quality are not known. We, therefore, conducted a randomized trial of blinded peer review. Each of 127 consecutive manuscripts of original research that were submitted to the Journal of General Internal Medicine were sent to two external reviewers, one of whom was randomly selected to receive a manuscript with the authors' and institutions' names removed. Reviewers were asked, but not required, to sign their reviews. Blinding was successful for 73% of reviewers. Quality of reviews was higher for the blinded manuscripts (3.5 vs 3.1 on a 5-point scale). Forty-three percent of reviewers signed their reviews, and blinding did not affect the proportion who signed. There was no association between signing and quality. Our study shows that, in our setting, blinding improves the quality of reviews and that research on the effects of peer review is possible. PMID- 2304217 TI - Effect of acceptance or rejection on the author's evaluation of peer review of medical manuscripts. AB - To determine whether authors of rejected manuscripts would evaluate the editorial review process less favorably than would authors of manuscripts accepted for publication, a questionnaire was sent to solicit evaluations of the quality of the reviews that had led to the rejection or acceptance of manuscripts submitted to the Journal of Pediatrics. Similar evaluations of the editor's letter were also sought. Authors were more likely to respond to the questionnaire if their manuscripts had been accepted and were more likely to complete the questionnaire thoroughly. Authors of accepted manuscripts evaluated the editor's communication more favorably than did the authors of manuscripts not accepted for publication, but the evaluations of the reviews were not significantly different. Most authors utilized the reviews to modify their manuscripts before submitting them to another journal. PMID- 2304218 TI - What can and should be done to reduce publication bias? The perspective of an editor. AB - "Publication bias" has three facets: (1) bias perceived by disappointed authors, (2) bias that journal policy may introduce, and (3) bias intrinsic in design and interpretation of the work itself. The third type, though a target of peer review, is not considered here, and the first type is more often imagined than real. However, general journals have to adopt policies on priorities that an outsider may see as bias, in the broadest sense. Opportunities for bias exist (18 varieties are listed here), but more objective evaluation is required before journals need to alter their peer review practices. In terms of work load and financial considerations, the price of some proposed correctives is high. Journals should monitor refereeing systems and allow appeals, but the case for policing systems--"blinding" referees (and, logically, editors), introducing tight codes of practice, and seeking solemn declarations of integrity, for example--needs more hard evidence. PMID- 2304219 TI - A cohort study of summary reports of controlled trials. AB - Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly. PMID- 2304220 TI - Underreporting research is scientific misconduct. AB - Substantial numbers of clinical trials are never reported in print, and among those that are, many are not reported in sufficient detail to enable judgments to be made about the validity of their results. Failure to publish an adequate account of a well-designed clinical trial is a form of scientific misconduct that can lead those caring for patients to make inappropriate treatment decisions. Investigators, research ethics committees, funding bodies, and scientific editors all have responsibilities to reduce underreporting of clinical trials. An extended use of prospective registration of trials at inception, as well as benefiting clinical research in other ways, could help people to play their respective roles in reducing underreporting of clinical trials. PMID- 2304221 TI - Comparison of research quality guidelines in academic and nonacademic environments. AB - Only 2 medical schools in the United States and Canada of 133 that responded to a survey have policy guidelines that address most of the significant ethical and procedural issues related to misconduct and fraud in biomedical research. Some nonacademic research environments have superior guidelines that offer useful models and deserve examination. Prevention of misconduct and fraud in biomedical research and reporting requires thoughtful, proactive change by academic and clinical institutions. While the causes of misconduct and fraud may be sufficiently complex to engender long debate, the methods for minimizing it are relatively straightforward and start with a clear statement of values and acceptance of responsibility. Otherwise, the failure of the biomedical research community to meet this challenge forthrightly is soon likely to lead to damaging intervention by government agencies and elected officials. The time to act is now. PMID- 2304222 TI - The philosophical basis of peer review and the suppression of innovation. AB - Peer review can be performed successfully only if those involved have a clear idea as to its fundamental purpose. Most authors of articles on the subject assume that the purpose of peer review is quality control. This is an inadequate answer. The fundamental purpose of peer review in the biomedical sciences must be consistent with that of medicine itself, to cure sometimes, to relieve often, to comfort always. Peer review must therefore aim to facilitate the introduction into medicine of improved ways of curing, relieving, and comforting patients. The fulfillment of this aim requires both quality control and the encouragement of innovation. If an appropriate balance between the two is lost, then peer review will fail to fulfill its purpose. PMID- 2304223 TI - NIH expects conflict-of-interest rule revisions to take at least 6 months. PMID- 2304224 TI - Researchers follow varied molecular paths toward better control of organ rejection. PMID- 2304225 TI - What will it take to recruit a new director for NIH? Advisory group has some suggestions. PMID- 2304226 TI - From the National Institutes of Health. PMID- 2304227 TI - From the Centers for Disease Control. Update: acquired immunodeficiency syndrome- United States, 1989. PMID- 2304228 TI - From the Centers for Disease Control. Tetanus--United States, 1987 and 1988. PMID- 2304229 TI - Physician participation in assisted suicide. PMID- 2304230 TI - The attitudes of students and house staff toward alcoholism. PMID- 2304231 TI - The compensation of physicians who treat patients having infusions at home. PMID- 2304232 TI - Conflicts of interest, continued. PMID- 2304234 TI - Autologous blood donations before elective cardiac surgery. PMID- 2304233 TI - Facts and artifacts about anemia and preterm delivery. PMID- 2304235 TI - Resident malpractice involvement debated by AMA-RPS. PMID- 2304236 TI - The accuracy of portable cholesterol analyzers in public screening programs. AB - To determine the accuracy of portable cholesterol analyzers in public settings, four screening organizations were accompanied to cholesterol screenings where consenting participants completed the finger-stick procedure and provided a blood sample by venipuncture. The finger-stick values were compared later with the participants' blood cholesterol values obtained in a reference laboratory. The results indicated that only one of the organizations produced cholesterol measurements entirely within the acceptable range (+/- 14.2%), while the accuracy of the other three organizations ranged from 76.5% to 96.4%. Those finger-stick values that did not fall within the acceptable range tended to underestimate the laboratory cholesterol values. Additionally, classification of the persons screened based on the National Cholesterol Education Program risk categories indicated that the finger-stick values primarily tended to produce false-negative results. The variability of the results across organizations was caused partially by insufficient operator training. However, inadequate quality-control procedures for field settings and dilution of capillary blood by tissue fluid also may have contributed to the inaccurate finger-stick results. PMID- 2304237 TI - The changing epidemiology of hepatitis B in the United States. Need for alternative vaccination strategies. AB - To determine trends in the incidence and epidemiology of acute hepatitis B in the United States we conducted intensive surveillance for viral hepatitis in four sentinel counties from October 1, 1981, to September 30, 1988. The overall incidence of hepatitis B remained relatively constant throughout the study period (average, 13.2 cases per 100,000 population), but disease transmission patterns changed significantly. The proportions of hepatitis B cases accounted for by homosexual activity and health care employment decreased 62% and 75%, respectively; the proportions of cases accounted for by parenteral drug use and heterosexual exposure increased 80% and 38%, respectively. The percentage of patients for whom no risk factor was identified (30% to 40%) did not change over time. These patients tended to belong to minority populations, and their socioeconomic level was low. The decline in the number of hepatitis B cases among homosexual men probably results from the modification of high-risk sexual behavior; the decline among health care workers is due mostly to hepatitis B immunization. The current strategy for prevention of hepatitis B, which targets high-risk groups for immunization, has failed to have a significant impact on the incidence of disease. PMID- 2304238 TI - A twin study of the effects of the Vietnam War on posttraumatic stress disorder. AB - This study evaluates the impact of military service during the Vietnam era (1965 to 1975) on posttraumatic stress disorder using a sample of 2092 male-male, monozygotic, veteran twin pairs. Data were collected in 1987 using mail and telephone interviews. In 715 monozygotic twin pairs who were discordant for military service in southeast Asia (SEA), posttraumatic stress disorder was found to be strongly associated with military service in SEA. The prevalence of posttraumatic stress disorder was 16.8% in twins who served in SEA compared with 5.0% in co-twins who did not serve in SEA. There was a ninefold increase in the prevalence of posttraumatic stress disorder (95% confidence interval, 4.8 to 17.6), comparing twins who experienced high levels of combat with their co-twin who did not serve in SEA. Our results demonstrate that nearly 15 years following the end of the Vietnam War, there remains a substantially increased prevalence of posttraumatic stress disorder among veterans who served in SEA. PMID- 2304239 TI - Dose-related effects of cigarette smoking on olfactory function. AB - Little is known about the influence of cigarette smoking on the ability to smell; previous studies on this topic have led to contradictory findings and have failed to take into account smoking dose and duration. In the present study, the 40 odorant University of Pennsylvania Smell Identification Test was administered to 638 subjects for whom detailed smoking histories were available. Smoking was found to be adversely associated with odor identification ability in a dose related manner in both current and previous cigarette smokers. Among previous smokers, improvement in olfactory function was related to the time elapsed since the cessation of smoking. Logistic regression analysis found current smokers to be nearly twice as likely to evidence an olfactory deficit than persons who have never smoked. Overall, the data suggest that (1) smoking causes long-term but reversible adverse effects on the ability to smell and (2) the failure of some studies to demonstrate smoking effects may be caused by the inclusion of persons with a history of smoking in the nonsmoking groups. PMID- 2304240 TI - How reliably can compact chemistry analyzers measure lipids? AB - Five compact chemistry analyzers were evaluated for the measurement of lipids. Fresh plasma or serum specimens from a standardized research laboratory were assayed for total cholesterol on all five analyzers. Triglycerides and high density lipoprotein cholesterol were assayed on the three analyzers that could measure both of these analytes. Study results were interpreted by assessing accuracy and precision and by defining the percentage of patient specimens classified in the same categories as the reference laboratory, according to National Cholesterol Education Program guidelines. Two analyzers met standards for accuracy of cholesterol measurement. Three analyzers met performance standards for precision of cholesterol measurement. Agreement with National Cholesterol Education Program classification of specimens compared with the reference laboratory for total cholesterol ranged from 73% to 96% and was less for indirect low-density lipoprotein cholesterol. We conclude that under controlled conditions, compact chemistry analyzers vary in the reliability of lipid determination and classification of patients. PMID- 2304241 TI - Cardiac risk classification based on lipid screening. PMID- 2304242 TI - A piece of my mind. A parting gift. PMID- 2304243 TI - Practice policies: where do they come from? PMID- 2304244 TI - [A complete relief of intractable postherpetic neuralgia with intrathecal methylprednisolone acetate]. AB - A 72-year-old man, 154 cm tall, weighing 53 kg was suffering from severe herpetic neuralgia on his left 10th intercostal nerve area. His pain continued even he was treated with frequent epidural nerve block (4 to 5 times per week) by an anesthesiologist. He was referred to our hospital on his 105th pain day. He complained severe continuous pain and numbness on his left 10th intercostal nerve area. Touching the painful skin induced lightning pain. His pain was so severe that his sleeping was disturbed and also he could not maintain his usual life. Epidural nerve block at 10th thoracic nerve was done with 20mg methylprednisolone acetate and 5ml of 1% lidocaine. After the treatment, his pain was reduced to 3/10 of the one he had on admission, and also his sleep was not disturbed further. Epidural nerve blocks with methylprednisolone weekly for a month induced no more remission. At his 154th pain day, a dose of 20mg methyl prednisolone acetate and 1% lidocaine 5ml was given intrathecally through 2nd lumber intervertebral space. The pain was relieved completely after the block. And he complained nothing about the skin area which had been disturbing his life for a long time. Auditory brainstem response which was recorded during the block showed prolongation of the latency of phase III and phase V at 40 minutes after the intrathecal injection of lidocaine. PMID- 2304245 TI - [Investigation of a patient with difficult endotracheal intubation]. AB - Unusually difficult endotracheal intubation was encountered during anesthetic induction of a 41-year-old male, necessitating use of a bronchofiberscope. The usual pre-operative analysis had shown no problems, such as tracheal tumor or stricture. Due to difficult intubation, post-operative evaluations were made and no abnormalities were found. However, investigation of the lateral roentgenogram showed a much greater than average backward bend in the patient's trachea under the vocal cord. It is likely that the sharp bend of the trachea was responsible for difficult intubation. PMID- 2304246 TI - [Anesthetic experience of a patient with essential thrombocythemia]. AB - We reported a 54-year-old male with essential thrombocythemia, who underwent coronary artery bypass grafting. Anesthesia was maintained with enflurane in nitrous oxide and oxygen supplemented with fentanyl. Heparin 7mg. kg-1 was administered intravenously to obtain adequate anticoagulant effect during 89 minutes of extracorporeal circulation. Aspirin and dipyridamole were also administered as anti-platelet therapy. No complications were observed during and after anesthesia. It is advocated that administration of anticoagulants such as heparin, aspirin and dipyridamole is effective to prevent thrombus formation. PMID- 2304247 TI - [Epidural morphine and buprenorphine for postoperative pain relief after hepatectomy]. AB - Postoperative pain relief with epidural morphine and buprenorphine was studied in 33 patients following hepatectomy. Morphine 2mg or buprenorphine 0.06mg in 10ml of normal saline was administered through an epidural catheter inserted at the Th10-11 or L3-4 interspace. Morphine injected at the lumbar level, as well as that injected at the thoracic level produced excellent and long-lasting (20.8 +/- 8.6 hours) pain relief. Respiratory rate decreased significantly following epidural morphine at the L3-4, but PaCO2 did not change. Buprenorphine injected at the thoracic level produced good and long-lasting (22.6 +/- 9.9 hours) pain relief, although buprenorphine injected at the lumbar level produced incomplete analgesia. The epidural administration of morphine 2mg at L3-4 or buprenorphine 0.06mg at Th10-11 may be recommended for postoperative analgesia following hepatectomy. PMID- 2304248 TI - [A method to predict pulmonary blood flow by nitrous oxide washout curve]. AB - The study was performed to obtain a relationship between the pulmonary blood flow and the tau b (time constant) calculated from multiple-breath nitrous oxide (N2O) washout curve. Elimination of N2O depends on pulmonary blood flow and alveolar ventilation. From the theoretical consideration, tau b can be calculated by the following formula; tau b = Vd[1/Qt-Qs) + 0.47/VA) Vd = N2O volume of distribution in the body Qt = cardiac output, Qs = shunt blood flow VA = alveolar ventilation. Relationship between observed Qt-Qs and observed tau b was admitted to the predicted formula. The method was compared with the thermodilution method in almost simultaneous measurement of the cardiac output. A good correlation was obtained between them (r = 0.87). Washout curve of nitrous oxide can be used for a reliable measurement of pulmonary perfusion. PMID- 2304249 TI - [Effects of turbulence on gas transport during high frequency oscillation]. AB - To clarify the enhancing effect of turbulence on gas transfer in high frequency oscillation (HFO), the role of turbulence during oscillatory flow was studied. Oscillatory flow was generated in a straight circular tube as a trachea model, over the range of Reynolds' number (Re: 2000-16000) and Stokes parameter (lambda : 3-7). This simulates clinical settings. Measurements of the axial velocity were made by means of hot wire anemometer, and turbulence intensity (I) as well as ensemble mean velocity was calculated. At the same time, 1 ml of 100% CO2 was injected into the tube, and CO2 concentration was measured by a CO2 analyzer to yield the effective diffusivity (Deff). As Re increases and lambda decreases to a certain level, "conditional turbulence" appears in the whole cross section to produce an efficient lateral mixing. Deff increases with increasing I as well as Re, and increasing lambda results in an increase in the difference of measured and theoretical Deff (Watson's prediction for laminar oscillatory flow). It is concluded that turbulence during oscillatory flow plays an important role in lateral mixing to facilitate gas transport, and decision of ventilator settings is essential so as to give rise to "conditional turbulence" for the purpose of Deff augmentation during HFO. PMID- 2304250 TI - [Reaction products of sevoflurane with components of sodalime under various conditions]. AB - Sevoflurane is reported to react with sodalime to resolve into several products. We examined the reaction products of sevoflurane when this anesthetic reacted with components of sodalime under various conditions. Analysis of reaction products was performed by gas chromatography using a 2m column packed with DOP. Six peaks including sevoflurane were detected on the gas chromatogram of sevoflurane after reaction with sodalime and five reaction products were obtained. These peaks were from P1 with the shortest retention time to P5 with the longest retention time. When sevoflurane was sealed with sodalime in a test tube at room temperature, only P1 was detected and all reaction products of P1 to P5 were identified when the test tube was heated at 50 degree C for 3 hours. Sodalime contains Ca (OH)2, NaOH, KOH and silicon dioxide. Reaction of sevoflurane with KOH produced P1 to P5 products even at room temperature. After the reaction of sevoflurane with NaOH or Ca (OH)2 at 50 degrees C, P1 to P5 or P1 only were detected on the chromatogram respectively. No peak of any reaction products was obtained after the reaction with silicon dioxide under various conditions. These results suggest that hydroxy group of sodalime component would increase reaction products of sevoflurane. PMID- 2304251 TI - [A simple method of extracorporeal membrane oxygenation (ECMO)--2: The effects of ECMO (arterio-venous shunt) on the arterial blood gases measured for 24 hours]. AB - In eight anesthetized mongrel dogs with thiopental, diazepam and pancuronium bromide, ECMO with arterio-venous shunt was performed under hypoventilation for 24 hours. The blood flow through the ECMO which was connected between the femoral artery and vein was approximately 40% of the cardiac output. Hypoventilation was induced to decrease PaO2 to around 40mmHg and increase PaCO2 to around 80 mmHg. The ECMO improved the abnormal parameters, which were induced by the hypoventilation, to almost normal range (PaO2 80mmHg, PaCO2 30mmHg) for 24 hours. Furthermore, there were no abnormalities in cardiovascular and other systems during ECMO. PMID- 2304252 TI - [Is MAC effected by liver dysfunction?--Bilirubin and MAC]. AB - If MAC is decreased in patients with liver injury, the amount of inhaled anesthetic administered to these patients could be reduced, and thereby reducing the impact of the anesthetic in such patients. The effect of jaundice in liver injury on halothane MAC was investigated in this study. After MAC for control was determined, 12 mongrel dogs received ligation of the common bile duct (CBD). MAC determination followed 1, 2, and 3 weeks after CBD ligation in 6 dogs in experiment 1. The other 6 dogs received bilirubin i.v. 1 week after CBD ligation, and MAC was determined before and after bilirubin, i.v. in experiment 2. Halothane was the only anesthetic used throughout the studies. In experiment 1, serum total bilirubin (TBil) increased to 7mg.d1-1; bilirubin did not enter the cerebro-spinal fluid (CSF); and MAC did not decrease significantly. In experiment 2, TBil increased to 21mg.dl-1; bilirubin entered the CSF; MAC significantly decreased 15% from control; and the correlation between MAC decrease and TBil increase was statistically significant (P less than 0.05). The results suggest that increase in serum bilirubin in liver injury will decrease MAC. PMID- 2304253 TI - [Usefulness of midazolam for premedication before local anesthesia]. AB - The optimal dose and adverse effects of midazolam for premedication were evaluated in 45 patients undergoing local anesthesia. The patients were divided into 3 groups and administered midazolam intramuscularly: group-A 0.075 mg.kg-1, group-B 0.1mg.kg-1, group-C 0.125 mg.kg-1. In this study, concerning sedative and hypnotic effects, the administration of midazolam (0.075-0.1mg.kg-1) showed satisfactory results except in conduction anesthesia of upper extremities (brachial plexus block). However, severe decrease in PaO2 was observed in relatively younger patients. Therefore, it is necessary to observe patients carefully during perioperative period. PMID- 2304254 TI - [The effect of craniotomy on lymphocyte subpopulations]. AB - The effect of craniotomy on cell mediated immunity was studied by using monoclonal antibodies and flow cytometry. Twelve patients undergoing craniotomy were investigated. Six patients had malignant brain tumor, four benign tumor, one AVM and one aneurysm. Examined lymphocyte monoclonal antibodies were Leu4, Leu2a and Leu3a. In addition, two color analysis using two monoclonal antibodies, Leu3a and Leu8, or Leu2a and Leu15, was performed. This technique can classify Leu3a positive cell into helper T cell and inducer T cell and Leu2a positive cell into suppressor T cell and cytotoxic T cell. The number of Leu4 positive cell (T cell) decreased during operation. The number of Leu3a positive cell (OKT4) also decreased at 30 minutes after incision and moderately recovered during operation. Leu2a positive cell (OKT8) did not show significant change. As the result, the decline of Leu3a/Leu2a ratio (OKT4/OKT8 ratio) was found after incision and this ratio gradually returned to preoperative level during operation. By two color analysis, decrease of inducer and helper T cell in Leu3a positive cell, and increase of suppressor T cell, and decrease of cytotoxic T cell in Leu2a positive cell were observed. The results of this study show that stress of craniotomy affected the immunological state. PMID- 2304255 TI - [Epidural buprenorphine with nitrous oxide-oxygen-enflurane anesthesia]. AB - Epidural buprenorphine (Bn) with nitrous oxide-oxygen-enflurane (GOE) anesthesia was investigated as an anesthetic method in 63 patients who underwent upper abdominal surgery over three hours. The patients were divided randomly into three groups. The first group received only GOE anesthesia (group A, n = 13), the second group was given GOE anesthesia and 0.2 mg epidural Bn every three hours during operation (group B, n = 23) and the third group was administered GOE anesthesia and 0.2 mg epidural Bn every six hours (group C, n = 27). The patients were rated according to intraoperative anesthetic dosage, awakening from anesthesia, postoperative respiratory depression and postoperative analgesia. The administered enflurane concentration declined approximately 0.4% in group B and C as compared that in group A (P less than 0.05). And there was no intra-group difference in the awakening time from anesthesia. Postoperative respiratory depression was noted in group B. The respiratory rate 18.7 +/- 1.0 (mean +/- SE) min-1 in group B was significantly lower compared with the rates 22.8 +/- 1.5 min 1 in group A and 22.1 +/- 1.1 min-1 in group C (P less than 0.05). The PaCO2 value 44.1 +/- 1.0 mmHg in group B was significantly higher compared with the values 39.8 +/- 0.8 mmHg in group A and 41.3 +/- 0.9 mmHg in group C (P less than 0.01). Postoperative analgesia was remarkably prolonged in group B and C; 542 +/- 97 minutes and 504 +/- 97 minutes, respectively, as compared with 55 +/- 20 minutes in group A (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304256 TI - [Accurate and simplified determination of ketamine in plasma by gas chromatography mass spectrometry]. AB - An accurate and simplified method has been developed for determination of ketamine in human plasma using gas chromatography and electron impact mode mass spectrometry with selected ion recording from 0.5ml of plasma. Standards and samples of plasma underwent the same procedure of two step extraction by methanol. Ketamine concentrations in the plasma were determined from the peak in the selected ion profile of ketamine (m/e: 237). Standard curve was linear with the increasing amount of ketamine (0.63-5.0 micrograms.ml-1) in plasma with mean CV = 5.2% mean RR = 63.8% and r = 0.998. The concentration of ketamine in plasma ranged from 1.6 micrograms.ml-1 to 2.5 micrograms.ml-1 during ketamine anesthesia (2mg.kg-1.h-1) in a surgical patient. PMID- 2304257 TI - [Let's study pharmacokinetics related to anesthesiology by using computer graphics: inhalation anesthetics]. AB - The pharmacokinetics of inhalation anesthetics has been out of public interest for 20 years. Partition coefficient or solubility of anesthetic, an important determinant of uptake and distribution of inhaled anesthetics, may be the only remains of the pharmacokinetics of inhaled anesthetics. There still, however, are a few evidences which can not be explained by partition coefficient of anesthetic. The authors applied three compartment model to the rise of the blood concentration of anesthetics, i.e., nitrous oxide, enflurane, halothane, and diethyl ether. We revealed that the change in the blood anesthetic concentration may be related to the size of compartments and their time constants. The size of compartments and their time constants may be determined by interaction of partition coefficient of anesthetic and blood distribution to the tissues which may be different with different anesthetic, and may also be different when the blood concentration of anesthetic is different. PMID- 2304258 TI - [Three cases with electrocardiographic changes suggesting myocardial infarction]. AB - We had three cases that showed electrocardiographic changes suggesting myocardial infarction during or soon after operation. All cases were elderly for open abdominal operation complicated with carcinoma or infection. They were different from typical myocardial infarction in progress of electrocardiographic changes, increase of myocardial enzyme, autopsy and so on. Kuramoto et al. reported in some cases myocardial infarction could not be recognized at autopsy in spite of electrocardiographic changes suggesting myocardial infarction during gastric operation of the elderly, and they advocated an idea of "reversible myocardial infarction". These three cases were also thought to be consistent with this disorder. PMID- 2304259 TI - [Coronary spasm during laryngoplasty]. AB - A 63-yr-old man weighing 56kg was scheduled for pharyngoplasty under general anesthesia. The patient had no history of ischemic heart disease. Preoperative ECG showed incomplete right branch block. We administered thiopental and succinylcholine for intubation. Anesthesia was maintained with enflurane, nitrous oxide, oxygen and pancuronium bromide. Thirty minutes after the start of incision, the patient developed a severe hypotension and ECG revealed ST elevation and complete AV block. We administered ephedrine hydrochloride, phenylephrine hydrochloride and atropine sulfate. The ECG returned to sinus rhythm but ST segment was depressed this time. We considered it due to coronary spasm, so we started continuous intravenous administration of nitroglycerin (0.5 microgram. kg-1. min-1). One hour later, ST segment returned to normal. ECG showed no remarkable changes and no symptoms were seen after the operation. We found it important to suspect coronary spasm when ECG showed PVC-like abnormal waves with ST elevation. We consider that continuous administration of nitroglycerin at a rate of 0.5 microgram. kg-1. min-1 was effective for the treatment of coronary spasm in this case. PMID- 2304260 TI - [Contrast-enhanced computed tomography in acute pancreatitis]. PMID- 2304261 TI - [Clinical criteria for the severity of acute pancreatitis proposed by the working group of the Ministry of Health and Welfare--assessment and problems]. PMID- 2304262 TI - [Circulatory failure in acute pancreatitis]. PMID- 2304263 TI - [Acute renal failure as a complication of severe acute pancreatitis]. PMID- 2304264 TI - [Hepatic insufficiency in severe acute pancreatitis]. PMID- 2304266 TI - [Gastro-intestinal complications in patients with severe acute pancreatitis]. PMID- 2304265 TI - [Respiratory failure in acute fulminant pancreatitis]. PMID- 2304267 TI - [Pathology of multiple organ failure in acute pancreatitis]. PMID- 2304268 TI - [Peritoneal lavage for severe acute pancreatitis]. PMID- 2304269 TI - [Intensive cares of severe acute pancreatitis]. PMID- 2304270 TI - [Surgical treatment of severe acute pancreatitis--indication for surgery and operative method]. PMID- 2304271 TI - [Diagnosis and clinical managements of late complications of severe acute pancreatitis]. PMID- 2304272 TI - [Review and prospect on management for pancreatitis]. PMID- 2304273 TI - [Definitions and classification of pancreatitis]. PMID- 2304274 TI - [Etiology and pathogenesis of acute pancreatitis]. PMID- 2304275 TI - [Histopathological classification of acute pancreatitis]. PMID- 2304276 TI - [Clinical symptoms of acute pancreatitis]. PMID- 2304277 TI - Non-invasive assessment of the steal phenomenon following femoro-femoral bypass. AB - Clinical studies were performed on 42 patients who underwent femoro-femoral bypass and postoperative assessment of the ankle/brachial pressure index (API) and Doppler waveform for each limb was carried out. Patients who had poor runoff of the donor limb showed a significant decrease in API after ankle joint exercise (p less than 0.05), whereas no significant change was observed in patients who had poor runoff of the recipient limb. The response of pulsatility index was similar to that of API. Thirteen of the 42 patients underwent both pre- and postoperative assessments. Six of these patients underwent additional procedures such as thromboendarterectomy or profundaplasty on the anastomotic site of the donor limb, and the other 7 patients had no additional procedures performed. A decrease in API after exercise was prominent in the patients who had not undergone any additional procedures, in the postoperative stage (p less than 0.01). Thus, when performing femoro-femoral bypass, improving poor runoff in the donor limb by carrying out intraoperative additional procedures should be taken into consideration, as any imbalance of peripheral resistance must be kept to an absolute minimum. PMID- 2304279 TI - Immunohistochemical and electron microscopic findings in a case of mixed hamartoma of the liver. AB - A case of mixed hamartoma of the liver in a 36 day old female infant is reported herein. The resected tumor was well demarcated, measured 7.5 X 7.0 cm and weighed 179 gm. Microscopically, the tumor was composed of loose fibrous stroma intermingled with spindle and polygonal cells and ductular structures. The spindle and polygonal tumor cells displayed the distinct cytoplasmic staining for alpha-1-antitrypsin. Most of the tumor cells showed the characteristic ultrastructural features of immature hepatocytes, having numerous cytoplasmic microvillous structures, abundant rough and smooth endoplasmic reticulum and mitochondria. These findings suggest that embryonic liver cells, which are capable of transforming into biliary structures and hepatocytes, serve as essential elements of mixed hamartoma of the liver. PMID- 2304278 TI - The pathophysiological characteristics of bile from patients with gallstones: the role of prostaglandins and mucin in gallstone formation. AB - Bile was obtained from 82 patients with various biliary tract diseases and concentrations of prostagloandins, leukotriens, mucin, and a number of lithogenic components were measured in order to evaluate the role of these substances in the pathogenesis of gallstone formation. The characteristics of bile in cases of cholesterol gallstones included high concentrations of prostaglandins and hexosamine and a high cholesterol saturation index. Prostaglandin E2 and prostaglandin F2 alpha concentrations in bile were correlated with hexosamine concentration, and prostaglandins and hexosamine were found to be actively synthesized and secreted in the gallbladder. Prostaglandins E2 and F2 alpha may therefore stimulate mucin secretion in the gallbladder with supersaturated bile. The characteristics of bile in cases of calcium bilirubinate gallstones included a high detection rate for bacteria, high beta-glucuronidase activity, a high percentage of unconjugated bilirubin, a low cholesterol saturation index and high concentrations of prostaglandins and hexosamine. Moreover, the synthesis and secretion of prostaglandins in the biliary tract were accelerated in cases of infected bile. Thus, hypersecretion of mucin, stimulated by prostaglandins, my participate in the onset and development of biliary tract infection or in the formation of calcium bilirubinate gallstones. Regarding the role of prostaglandins and mucin, the hypotheses for gallstone formation previously reported by many authors are supported by the clinical data obtained in the current study. PMID- 2304280 TI - A tuberculous pseudoaneurysm of the thoracic aorta presenting as massive hemoptysis--a case of successful surgical treatment. AB - Tuberculous aneurysms of the aorta need early diagnosis and prompt surgical intervention because if untreated, they lead to severe consequences. We report herein, a case of a 63 year old woman who underwent successful resection of a tuberculous pseudoaneurysm which had ruptured into the left upper lobe of the lung after a punch biopsy, performed under bronchoscopy, had caused severe bleeding. Subsequent CT and MRI examinations suggested a fistula between the mass and the aorta and proved useful in establishing the diagnosis of a pseudoaneurysm. We wish to emphasize the need for bronchoscopy to be done carefully because of the risk of inducing massive hemoptysis. PMID- 2304281 TI - A small early carcinoma of the stomach with extra-perigastric lymph node metastasis: a case report. AB - An early gastric carcinoma, measuring 1.7 X 0.6 cm, had already metastasized to the extra-perigastric lymph node in a 71 year old symptom-free man. Radiographic and endoscopic studies showed a small depressed lesion on the lesser curvature of the antrum and histology of the biopsied specimen revealed a well differentiated adenocarcinoma. Under the diagnosis of IIc type intramucosal carcinoma, partial gastrectomy and wide lymph node dissection was performed. Pathologic study of the resected specimen showed that the cancer cells had invaded the submucosa at an area via a lymphatic vessel and that only one lymph node along the common hepatic artery was involved. PMID- 2304282 TI - Nuclear DNA content in breast carcinoma with special reference to the parameters of malignant potentiality. AB - Nuclear DNA ploidy pattern was examined in 22 breast carcinomas with a tumor mass of up to 2.2 cm and compared with the clinical and histological parameters of the malignant potentiality of breast carcinomas. The 22 carcinomas were divided into 11 aneuploid and 11 near-diploid carcinomas. It was found that the histological type, histological grade, nuclear grade, mitotic index and lymphatic invasion were either only slightly, or not correlated at all with the DNA ploidy pattern. Nevertheless, lymph node metastasis and negative estrogen receptor status was more frequently seen in the patients with aneuploid carcinoma than in those with near-diploid carcinoma. PMID- 2304283 TI - The influence of hyperthermia in vitro on the functions of peritoneal macrophages in mice. AB - Total-body hyperthermia (TBHT) as a treatment for cancer may lead to a reduction in the host's immunocompetence as a result of the direct effects of heat on the immune system. Thus, we studied the influences of hyperthermia in vitro on the function of peritoneal macrophages from mice. Peritoneal macrophages from C3H/HeN mice were heated in vitro for 3 hr at 37, 39, 40, 41 or 42 degrees C. After exposure to heat, the phagocytic ability of the macrophages, as well as results of the nitroblue tetrazolium (NBT) reduction test and the cytotoxicity test were examined. The changes in all these parameters showed almost the same pattern: a tendency for macrophage functions to be potentiated up to 40 degrees C, and a tendency towards inhibited functioning at temperatures above 41 degrees C. Although augmented functions of macrophages were observed after exposure to mild hyperthermia (less than 40 degrees C), the possibility of TBHT (42 degrees C) induced inhibition of macrophage function must be further investigated in clinical trials of TBHT therapy for cancer. PMID- 2304284 TI - A proposal of indices to describe the carcinoembryonic antigen time course in in order to assess the effects of treating recurrent colo-rectal carcinoma. AB - In order to assess the effects of treating recurrent or non-resectable colo rectal cancer, the following 5 indices for the serum CEA time course were devised: 1. If the serum CEA doubling time is altered by any treatment from D1 to D2 we term D2/D1 as the "CEA doubling time ratio" of the treatment; 2. the per cent decrease in the serum CEA level from CEA1 to CEA2 is calculated by (logCEA1 logCEA2) X 100/logCEA1; 3. the period when the CEA level has returned to normal after a treatment is termed the "normalization period"; 4. "backward time retrieval" is the period between the lowest point of the posttreatment CEA and the crossing-point of this level by the pretreatment rising slope and; 5. "forward time earning" can also be defined. By using these indices, surgical treatments resulted in a higher per cent decrease in CEA, a longer normalization period but a shorter doubling time when the tumor recurred. PMID- 2304285 TI - Clinical experience of biliary tract carcinoma associated with anomalous union of the pancreaticobiliary ductal system. AB - Between 1978 and 1988, 15 patients with gallbladder cancer and 2 patients with bile duct cancer were seen among 49 patients with anomalous union of the pancreaticobiliary ductal system. Radiographic findings revealed two types of this anomalous condition: one in which the pancreatic duct entered the common bile duct (type 1) and one in which the common bile duct entered the pancreatic duct (type 2). In gallbladder cancer, the common bile duct presented no dilatation, or in some patients, mild dilatation, and type-1 anomalous union was frequently found among these patients. In contrast, the two patients with bile duct cancer had cystic dilatation of the common bile duct and type-2 anomalous union. The bile amylase level, which was determined in seven patients, was extremely high in all the patients. Histopathologically, the tumors in most patients showed papillary to papillo-tubular proliferation in the mucosal layer while atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that this congenital anomaly in both ducts results in a loss of the normal sphincteric mechanism of the duodenal papilla, and that chronic relapsing cholecystitis or cholangitis, caused by the reflux of pancreatic juice into the biliary tract, can induced progressive changes to atypical epithelial hyperplasia which may develop into carcinoma. PMID- 2304286 TI - Left ventricular function in the early postoperative stage--cardioplegic baneful effect is lost in the first 24 hours. AB - Early postoperative left ventricular function was investigated in 42 patients with left ventricular volume overload caused by valvular regurgitation. Preoperatively, left ventricular contractile function, stroke work and stress relations were all evaluated. Anoxic index (AnI) was considered as an index of myocardial preservation. Postoperatively, the cardiac function was estimated as the left ventricular stroke work index (SWI) after 3, 6, 24 and 48 hours of post cardiopulmonary bypass. The release of CK-MB isoenzyme was also measured at the same time as an indication of myocardial injury. AnI and the postoperative SWI3 and SWI6 showed negative correlations in 6 hours, while preoperative SWI0 and postoperative SWI24 and SWI48 showed positive correlations after 24 hours, and SWI0 showed positive or negative correlations to the preoperative 8 parameters. It was observed that ejection fraction, end-systolic wall stress to end-systolic volume index ratio and tension volume ejection showed positive, while left ventricular end-diastolic pressure showed negative correlations to SWI48. However, none of these indexes showed any significant correlations during the first 24 hours following surgery. On the other hand, AnI and the total release of CK-MB isoenzyme showed a positive correlation. These data suggest that the cardioplegic baneful effect on cardiac function might be lost in the first 24 hours after surgery. PMID- 2304287 TI - Computed tomography and nonoperative treatment for blunt abdominal trauma. AB - Studies were undertaken to determine if computed tomography (CT) could reliably assist physical examination in the initial assessment of blunt abdominal trauma, and also to examine how various abdominal injuries were managed with the guidance of CT. A total of 255 patients underwent emergency abdominal CT following blunt abdominal trauma over a period of seven years. One hundred and fifty two patients had abnormal CT scans, including 58 hepatic, 36 renal, 25 splenic and 9 pancreatic injuries as well as 67 patients with intra-abdominal hemorrhage and 21 patients with free abdominal air. A comparative study on the detection of pneumoperitoneum revealed CT to be far superior to plain radiography. One hundred and three patients had normal CT scans, all of whom were managed nonoperatively, except for three false-negative cases and two nontherapeutic cases. The patients with injury to the parenchymal organs were given nonoperative treatment if they had stable vital signs and no evidence of associated injuries demanding immediate surgery and the majority of these patients were managed well nonoperatively. CT was thus found to be a useful adjunct in the management of victims of blunt abdominal trauma, since in a rapid and noninvasive fashion, CT accurately defined the extent of parenchymal organ injury and also disclosed any other abdominal injuries. PMID- 2304288 TI - Endoscopic and manometric study of the cardia in post-gastrectomy patients. AB - This study was undertaken to clarify the incidence of hiatus hernia and the functional changes in the cardia of post-gastrectomy patients. One hundred and four post-gastrectomy patients and 399 non-gastrectomy patients were selected for endoscopic study, and the diagnosis of hiatus hernia was made by observing the shape of the cardia inside the stomach. A manometric study was also done on 12 patients with gastric carcinoma and 14 patients with gallstones. Hiatus hernia was observed in 37.5 per cent of the post-gastrectomy patients, this incidence being significantly higher than the 19.3 per cent of the non-gastrectomy patients (p less than 0.01). In the latter group alone the incidence of hernia steadily increased with advancing age. In the post-gastrectomy patients, reflux esophagitis and heartburn were observed in 20.2 per cent and 27.9 per cent, respectively. These incidences tended to be higher in the patients with hernia but there were no significant differences. The manometric study revealed that lower esophageal sphincter pressure was significantly decreased after gastrectomy, but not after cholecystectomy. PMID- 2304289 TI - Characterization of urinary peptic activity after total gastrectomy. AB - Urinary peptic activity, which has always been thought to originate from only the gastric mucosa, was detected in 26 of 50 totally gastrectomized patients with a mean value of 167 +/- 30 ng/ml. The gel filtration analysis suggested that the peptic activity of urine after total gastrectomy was detected at the same fractions as those of pepsinogens. Moreover, electrophoretical analysis of urine after total gastrectomy showed that the peptic activity was detected at the same distance as that of group I pepsinogen. The immunoreactive pepsinogen I in the urine and serum was then examined by radioimmunoassay. Pepsinogen I was detected in the urine of all the patients who had undergone total gastrectomy, the mean value of urinary pepsinogen I being 32.2 +/- 3.83 ng/ml. In 38 of 40 cases, pepsinogen I was detected in the serum at a mean value of 4.17 +/- 0.51 ng/ml. Moreover, the peptic activities and immunoreactive pepsinogen I levels in the urine correlated well. These results suggested that urinary peptic activities detected after total gastrectomy were due to the pepsinogen I previously believed limited to the gastric mucosa. The extra-gastric production of pepsinogen I was therefore strongly suggested. PMID- 2304290 TI - The antitumor effects of locally injecting human peripheral blood mononuclear cells treated with OK-432 into the tumor site: the possible role of a tumor growth inhibitory factor (TGIF). AB - The production of a tumor growth inhibitory factor (TGIF) was induced in human peripheral blood mononuclear cells (PBMC) by a streptococcal preparation, OK-432, in vitro. The antitumor effect of locally injecting PBMC treated with OK-432 into the tumor site was studied. PBMC were collected from patients with gastric cancer 5 to 12 days before their operation, and cultured with OK-432 for 24 hr in vitro. After the culture, the PBMC were washed thoroughly to eliminate the OK-432. The washed PBMC went on producing TGIF for more than 72 hr in vitro in the absence of OK-432. A small number of TGIF-producing PBMC, approximately 10(7) cells, were injected around the lesion under endoscopic observation. A remarkable antitumor effect was observed in 2 out of 10 cases of resectable gastric cancer. Histological examinations indicated that the antitumor effect is due to antitumor cytokines such as TGIF produced by PBMC rather than to the OK-432-activated PBMC themselves. PMID- 2304291 TI - Radiation-induced esophageal cancer: a case report and a review of the literature. AB - A 63 year old woman who had been irradiated for thyroid carcinoma at 36 years of age developed a cervico-esophageal stricture, the biopsy specimens from which revealed squamous cell carcinoma. Total esophagectomy was performed and a small linear ulcer was found in the resected specimen. Histological examination revealed moderately differentiated squamous cell carcinoma with severe fibrosis around the tumor, indicating radiation-induced cervical esophageal cancer. The characteristics of radiation-induced esophageal cancers described in the literature are reviewed in context of the present case. PMID- 2304292 TI - [Comparative study of aorto-coronary bypass surgery using internal mammary artery grafts and saphenous vein grafts]. AB - From April, 1985, through March, 1988, 202 patients had aorto-coronary artery bypass (CABG). In two series of consecutive patients who underwent CABG alone with the saphenous vein (SVG) or the internal mammary artery (IMA), mortality, morbidity and postoperative angiographic findings were compared with two series. The mean number of grafts placed was 1.8 per patient (1 to 4 grafts) in IMA group and 2.2 per patient (1 to 4 grafts) in SVG group. Mortality was 3% in two groups. The intraoperatively mean blood flow of graft to LAD in SVG and the mean blood flow of free end of IMA had no significant difference. The early patency rate (1.5 months) was 96% for 177 grafts in IMA group, 97% for 100 with IMA-LAD anastomosis, and 95% for 221 grafts in SVG group, 97.7% for 88 with SVG-LAD anastomosis. Morbidity was not significantly different. Many reports suggested that the long-term patency rate was good within the IMAG. In conclusion, the usefulness of IMAG in Japanese patients should be more stressed in young patients. PMID- 2304293 TI - [Epidural morphine as a sedative after open heart surgery: in cases of coronary artery bypass graft]. AB - 20 cases of coronary artery bypass graft (CABG) were divided randomly into 2 groups. 10 cases (Group I) received epidural catheterization between Th 6/7 at least 24 hours prior to the operation. After operation, these 10 cases were sedated with 3 mg of Morphine hydrochloride given through the epidural catheter. Other 10 cases (Group II) were sedated with 10 mg of Morphine given intravenously. Parameters of cardiorespiratory dynamics such as arterial blood pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure, oxygen saturation of mixed venous blood, cardiac index, doses of intravenous Nitroglycerin, Dopamine and Dobutamine, arterial blood gas analysis were measured and compared in two groups. No side effect caused by the epidural catheter was found in Group I. Parameters with significant difference in two groups were only doses of Dopamine and base excess from blood gas analysis, but these were not due to the method of sedation. Frequency of the sedation needed within 24 hours after operation was fewer, and the condition of the sedation was better in Group I. The course of postoperative management had no difference between both groups. Epidural Morphine was concluded to be an employable method of sedation after CABG. PMID- 2304294 TI - [Long-term follow-up study of the surgical treatment of pulmonary adenocarcinoma]. AB - The surgical treatment of pulmonary adenocarcinoma was studied on the basis of the postoperative long-term results in 211 cases. The overall five-year survival rate was 42% for adenocarcinoma and 48% for squamous cell carcinoma, and there was no significant difference. In stage I, as the degree of differentiation became lower, the prognosis became poorer. In stage III, the five-year survival rate was 50% for the alveolar cell type and 32% for the well differentiated type. The prognosis was better than in the moderately or poorly differentiated types. The prognosis of T1N0 cases was 79% in T1, but it was significantly lower 39% for T2 cases. Among T3 or T4 cases other than N2, the two-year survival rate was 15%, and the longest survival recorded was 32 months. The results were also poor in 9 cases undergoing extensive surgery, with the two-year survival rate being only 10%. Of the N2 cases undergoing extensive surgery all died within a year, except for one case surviving two years following panpleuro-pneumonectomy. In N2, the prognosis was significantly worse if there were two or more foci of mediastinal lymph node metastasis or if subcarinal lymph node metastasis was present. In the long surviving cases, cancer-bearing survivors were about twice as common as with squamous cell carcinoma. Recurrence was usually by distant metastasis (mainly to the brain), being twice as common as local recurrence. Therefore, in adenocarcinoma the significance of postoperative adjuvant therapy was considered to be greater than in squamous cell carcinoma. PMID- 2304295 TI - [Laser ablation in the treatment of ventricular tachycardia: problems in the clinical case]. AB - I. Experimental Studies We examined if laser ablation could make the same characteristic lesion as cryolesion to canine myocardium. Nine mongrel dogs were used in this experiment. Right lateral thoracotomy was performed and Nd:YAG laser was delivered onto the epicardial surface of both ventricles. Laser power of between 10 and 50 W was used with the various duration of 3 and 20 s, keeping the lasing distance 5 mm above the cardiac surface. Histologically, the lesion showed a well-demarcated area consisted of coagulation necrosis and contraction band necrosis in the acute phase, which changed to a fibrous scar in the chronic phase. There was a good correlation (r = 0.79; n = 52, p less than 0.01) between the lasing energy and the depth of the denaturation zone. II. A Case Report A 45 year-old male with ventricular tachycardia (VT) after aortic valve replacement was operated upon with Nd; YAG laser delivery. An antero-lateral thoracotomy through 4th and 6th inter-costal space was performed. The intraoperative mapping showed the three origins of VTs to be near the apex of left ventricle. With cardiopulmonary bypass, Nd; YAG laser was delivered onto the endocardial surface adjacent to arrhythmogenic foci. The lasing power was 10-30 W with the duration of 5.0-9.9 s. One hundred twenty seven trials were done with the total lasing energy to be 12490 J. Subsequently cryoablation was added on this area. Though VT remained in acute phase, 2 weeks later, all of tachyarrhythmia was abolished spontaneously. PMID- 2304296 TI - [Transesophageal echocardiography during coronary bypass surgery]. AB - Transesophageal two-dimensional echocardiography (TEE) was evaluated in 14 patients who underwent coronary bypass surgery. The TEE transducer was positioned to view the left ventricular short axis at the level of the papillary muscle. Global left ventricular function was assessed by measuring left ventricular end diastolic and end-systolic area and computing the fractional area change (FAC). Regional left ventricular function was analyzed after dividing the short axis view of the left ventricle into four anatomic segments. The mean FAC was 48% after intubation, 48% after skin incision, 47% after sternotomy, and 51% after pericardiotomy. The mean FAC increased significantly to 55% 0 to 30 minutes after cardiopulmonary bypass, and was 53% at the end of the operation. In 5 patients, FAC decreased and regional wall motion abnormalities appeared around sternotomy. These abnormalities was considered due to transient myocardial ischemia. In 7 patients, a paradoxical motion of the ventricular septum occurred at closing of the sternum. TEE was performed without complication and found to be a good method for assessing global and regional left ventricular function. PMID- 2304297 TI - [Combined operation for renovascular hypertension and ischemic heart disease]. AB - We have experienced two patients of ischemic heart disease associated with renovascular hypertension. Patient 1 (60-year-old man) underwent LV aneurysmectomy and triple aortocoronary bypass grafting (saphenous vein to diagonal branch, left internal mammary artery to obtuse marginal branch, and right gastroepiploic artery to right coronary artery). Seventy five days after the initial cardiac surgery endarterectomy for the left renal artery and bifurcated Dacron graft implantation for the iliac artery obstruction were performed. Patient 2 (62-year-old woman) underwent simultaneous operation of both right nephrectomy and triple aortocoronary bypass grafting (saphenous vein grafts to obtuse marginal branch and right coronary artery, and left internal mammary artery to left anterior descending artery). Their postoperative courses were uneventful except unstable and high blood pressure for four to seven days after the operation. It appears that it should be decided to achieve either simultaneous or two stage approach for ischemic heart disease associated with renovascular hypertension based on the preoperative cardiac function. And both postoperative cardiac function and hypertension should be carefully managed until the blood pressure becomes stable after the surgery. PMID- 2304298 TI - [Extensive surgical treatment of advanced or recurrent carcinoma of the thyroid gland: report of three cases]. AB - Three advanced or recurrent thyroid carcinomas invading the adjacent surrounding organs such as trachea, great vessels or anterior mediastinum were reviewed. In one patient, resection of subtotal thyroid combined with trachea including a part of cricoid cartilage was performed, and followed with end to end anastomosis. In the other two patients with SVC syndrome, a trans-sternal surgical approach was applied in order to resect a large tumor extending into the anterior mediastinum. Replacement of SVC with ringed PTFE graft and chest wall resection was performed in one patient. With these extended surgical intervention, more operative radicality, prolonged surviving time and better quality of life were expected. PMID- 2304299 TI - [Staged operation for supravalvular aortic stenosis syndrome associated with severe multiple peripheral pulmonary stenoses: a case report and surgical methods]. AB - Successful surgical correction of supravalvular aortic stenosis (SAS) syndrome associated with severe peripheral pulmonary stenosis by a staged approach in a 6 year-old boy is reported. Right ventriculogram demonstrated bilateral severe peripheral pulmonary stenoses and cardiac catheterization revealed severe pressure gradient of 94 mmHg between the trunk of pulmonary artery and right and left peripheral pulmonary arteries, respectively. Bilateral severe peripheral pulmonary stenoses were relieved successfully by staged operations. Initially, a stenotic portion of the right pulmonary artery and its bifurcation was removed and a DeBakey Knitted Dacron graft was interposed between the right pulmonary artery and the peripheral pulmonary artery which was enlarged by arterioplasty. Nine days later, stenosis of the left peripheral pulmonary artery was relieved by arterioplasty using a Rygg patch. Finally, 8 months after the initial operation, the patient underwent definitive repair of SAS by extended aortoplasty. The postoperative course of the patient was uneventful. Our experience indicates that in the surgical treatment of the patient with SAS and associated severe multiple peripheral pulmonary stenoses, a staged approach, that is initial staged repair of the bilateral pulmonary stenoses by arterioplasty through thoracotomy followed by definitive intracardiac repair of SAS, is the procedure of choice. PMID- 2304300 TI - [Pulmonary annuloplasty in functional pulmonary regurgitation associated with mitral stenosis: a case report]. AB - In order to prevent disadvantage of pulmonary regurgitation (PR) on cardiac function, pulmonary annuloplasty (PAP) was performed in a 58-year-old female. She suffered from severe mitral stenosis with right heart failure, and was in a state of cardiac cachexia. She was associated with PR due to pulmonary annular dilatation secondary to severe pulmonary hypertension. She underwent mitral valve replacement, tricuspid annuloplasty and PAP around the pulmonary annulus using a Teflon tape. No PR was observed by postoperative angiograms, and the operative method was proved to be effective on the treatment for PR. The PAP is recommended for patients with functional PR secondary to severe pulmonary hypertension. PMID- 2304301 TI - [A successful surgical treatment of WPW syndrome associated with tricuspid atresia]. AB - The occurrence of both tricuspid atresia and WPW syndrome is quite rare. To our knowledge, only two operated cases have been reported. In this report, a 8-year old boy with this combination was reported. Tachycardia via the right side accessory pathway was for the first time pointed out after Kreutzer's operation. Epicardial mapping showed the earliest excitation at the right free wall. When fatty tissue around this area was removed by CUSA, a large cardiac vein appeared. By holding this vein with a forceps, the delta wave disappeared temporarily. ACP seemed to be present near this vein. Permanent disappearance of the delta wave was obtained after ligation and division. Four months after surgery, he is free from tachycardia attacks. PMID- 2304302 TI - [A case report of combined composite valve graft replacement of the aortic root and graft replacement of the abdominal aorta]. AB - A 55-year-old man who had both aortic root aneurysm with severe aortic regurgitation and enlarging abdominal aortic aneurysm was admitted to our hospital. We employed the combined composite valve graft replacement of the aortic root and Y-graft replacement of the infrarenal abdominal aorta at one stage operation. At the operation, median sternotomy was made and the composite graft replacement of the aortic root was performed under cardiopulmonary bypass prior to the abdominal procedure. After cardiopulmonary bypass was removed, abdominal incision was made. Although ventricular arrhythmias and mild hypotension transiently occurred when the abdominal aorta was clamped, the Y graft replacement was also completed uneventfully, and no complication occurred postoperatively. We conclude that the combined operation of the aortic root and the abdominal aorta is clinically feasible in certain situation. PMID- 2304303 TI - [Hamilton's operation in Bland-White-Garland syndrome]. AB - A 14-year-old boy, who had been treated medically for mitral regurgitation, underwent cardiac catheterization which revealed not only mitral regurgitation but also anomalous origin of the left coronary artery from the pulmonary artery. Thus he was diagnosed as Bland-White-Garland syndrome which was repaired by Hamilton's operation. Under cardiopulmonary bypass, the pulmonary trunk was opened longitudinally. After aorto-pulmonary window (A-P window) was created, a heterogenous pericardial baffle was attached to the posterior wall of the pulmonary trunk connecting A-P window and the ostium of left coronary artery. Thereafter the pulmonary trunk was enlarged with a patch of the same material. He did well postoperatively. Postoperative angiogram demonstrated satisfactory reconstruction of two-coronary-artery system. PMID- 2304304 TI - [Left ventricular rupture following the procedure of percutaneous transluminal coronary angioplasty: a case report]. AB - A 50-year-old man with 90% concentric stenosis at the proximal portion of the left anterior descending artery was tried to be treated with percutaneous transluminal coronary angioplasty (PTCA). The guide wire did not pass through the stenotic portion, and the staining out of coronary artery was recognized. Four hours after the procedure, he fell to shock status with a sign of electro mechanical dissociation. An emergent operation confirmed the left ventricular rupture. Repair of the tear and saphenous vein bypass to the left anterior descending artery were performed rapidly, however, he was not weaned from cardiopulmonary bypass. Close communication between cardiologist and surgeon, and immediate surgical back up are essential for saving these patients from severe ischemic events following PTCA failure. PMID- 2304305 TI - [A case report of the pectoralis major muscle flap in the successful management of severe mediastinal infection]. AB - A severe, post-mediansternotomy, mediastinitis was treated with pectoral muscle flap method. About 10 days after CABG this patient had purulent discharge, high fever, and unstable sternum. Under a diagnosis of mediastinitis, wound irrigation and systemic administration with antibiotics began, but these managements were ineffective. Therefore, we closed the chest primarily by the pectoral muscle flap method. Successful primary closure of the chest was accomplished. PMID- 2304306 TI - [Pure aortic regurgitation due to congenital bicuspid valve: a case report]. AB - A rare case of pure severe aortic regurgitation (AR) accompanied with congenital bicuspid aortic valve is presented. A 36-year-old female was admitted with rapid development of congestive heart failure. Examinations clarified severe AR with congenital bicuspid valve. Either calcification or vegetation on the valve was completely denied. At operation, both leaflets were apart from each other with a distance of 7 mm at the anterior commissura. A mechanical valve (Bjork-Shiley 23A) was sutured and she has been well. Pathological study of the resected leaflets revealed neither calcium deposit nor finding of infection but collagenous fibrous tissue with focal mucinous degeneration. A few cases of AR with bicuspid aortic valve have been reported in patients of annuloaortic ectasia. The partial annular ectasia was suspected as the cause of solitary aortic regurgitation with bicuspid aortic valve in our case. PMID- 2304307 TI - [Study on adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) for renal cell carcinoma--amplification of IL-2-elicited TIL proliferation by OKT3 monoclonal antibody]. AB - Human autologous peripheral blood lymphocytes (PBL) and lymphocytes infiltrating renal cell carcinoma (TIL) were cultured with medium containing 1000 IU/ml of human interleukin 2 (IL-2). A high cytotoxic activity against fresh autologous as well as cultured allogenic tumor cells was developed. By culturing these lymphocytes with OKT3 monoclonal antibody during the initial 2 days of long-term culture, in terms of T cell activation signal, IL-2-driven lymphocyte proliferation was remarkably accelerated with maintenance of appreciable level of cytotoxic activity. The same culture method also induced an increase in OKT3 and IL-2 receptor positive lymphocyte population in LAK cells and TIL. This method may enable us to gain more autologous TIL in vitro for adoptive immunotherapy of renal cell carcinoma than the usual culture method with IL-2 alone. Five patients with metastatic renal cell carcinoma were treated with adoptive immunotherapy with TIL, LAK and IL-2. One patient with pulmonary metastasis has had a minor response which has lasted for 3 months so far. We have not experienced any serious side effects during the treatment. PMID- 2304308 TI - [Statistical evaluation of determinants of progression of superficial bladder cancer by proportional hazards model]. AB - To evaluate clinical and pathological factors present at the initial consultation which affect disease progression, we reviewed data from 223 patients with superficial bladder cancer (pTa and pT1) who were initially treated at Nagoya University Hospital between January 1973 and December 1987. The factors included in the present analysis were age, sex, symptoms, interval between initial symptoms and first consultation, location of tumor, size, number, endoscopic shape, histological pattern of growth, grade and stage. The median duration of the follow-up after initial treatment was 46 months. Of the 223 patients, 17 died: 8 (3.6%) of bladder cancer and the remaining 9 (4.0%) of unrelated causes. Disease progression developed in 12 patients (5.4%): muscle invasion of the bladder wall in 11 and lung metastasis in one. The interval between initial treatment and progression ranged from 4 to 108 months, with a median of 11.5 months. Of the 12 patients, 9 (75%) had disease progression within 2 years. Progression was significantly associated with poor prognosis (p less than 0.001): the 5-year actuarial survival rates were 47.1% and 92.8% in patients with and without progression, respectively. Univariate analysis by Cox's proportional hazards model demonstrated that characteristics such as irritative bladder symptoms, higher-grade tumors, invasion into lamina propria, and nonpapillary growth seen at initial consultation were significantly related to disease progression. Cox's proportional hazards model produced hazard ratios of 10.2 in irritative bladder symptoms (yes vs. no), 6.3 in histological grade (grade 3 vs. grades 0-2), 4.9 in stage (pT1 vs. pTa), and 4.7 in pattern of growth (papillary vs. nonpapillary).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304309 TI - [A case of neurogenic bladder due to arachnoid cyst of the middle cranial fossa]. AB - A 6-year-old girl, with urinary incontinence for the past 3 years, showed an overactive bladder and detrusor-sphincter dyssynergia (DSD) in urodynamic study. An epileptic focus in the right occipital area, as well as a large arachnoid cyst in the left middle cranial fossa was revealed by EEG and intracranial CT. After surgery for the arachnoid cyst, urinary incontinence was improved with disappearance of the epileptic focus in EEG, and an alteration of overactive bladder into normolactive one and improvement of DSD were observed in urodynamic study. It was considered that the urinary incontinence of this case might be associated with the ectopic epileptic focus due to the arachnoid cyst. PMID- 2304310 TI - [The method of total heminephroureterectomy--application of mucolysis]. AB - Double ureters are not a rare anomaly. In the great majority of duplex-ureter systems, both components are functionally normal. Some may present medical problems such as abdominal cystic masses and recurrent urinary tract infections, even from the newborn period. The choice of the best method of the operation depends on residual renal function, the form of ureters, the shape and the position of the ureter orifice, and other factors. So, there are many methods by which to operate on duplex-ureter systems. Total heminephroureterectomy may be the best method of choice, if the duplex-ureter portion is non-functional. It is however, very difficult to resect the pathological ureter with the mate ureter uninjured, when the mate is covered by a common sheath or the patient is very small. Recently, two patients were admitted to our hospital because of abnormal findings of intrauterine echogram. One of them had a large ureterocele with a dilated ureter whose upper pole duplex kidney was non-functioning and cystic. The other patient had an upper ureter orifice opening ectopically to vagina, a ureter dilated, and a non-functioning upper ple duplex kidney. For heminephroureterectomy, resection of the upper one-fourth of the upper pole ureter was easy. But further excision of ureter seemed threatening to the mate ureter. We applied the mucolysis method, which we had been using as the operation of Sowve's method for the patients with Hirschsprung diseases. The method was technically easy and safe. There have been no complications after 1 year of follow up. PMID- 2304311 TI - [Effects of long-term administration of furosemide on calcium balance, kidney and parathyroid gland]. AB - Furosemide, a potent natriuretic agent, is well known to increase urinary calcium excretion. We study the effects of long term administration of furosemide on the calcium balance, renal function and histopathological changes of the kidneys and the parathyroid glands in the rat. Furosemide (20 mg/kg) was administered 3-4 times per week for 62 weeks intraperitoneally in 10 male rats. The same volume of normal saline was administered intraperitoneally in 9 male rats as control. All were given with standard diet (CE-2) and deionized water. While urinary calcium and creatinine were measured every 1-4 weeks, serum calcium and creatinine were measured in the first week and at the end of examination. 24 hours urinary excretion of calcium was elevated to two to three folds (a significant increase over the control: p less than 0.01) after the furosemide loading, though serum calcium and creatinine levels remained as in control. Despite a marked hypercalciuria in the furosemide loaded rats, there was no evidence of stone formation in the kidney or in the urinary tract. On histopathological examination renal parenchyma showed some pyelonephritic changes but without evidence of crystal formation, while no significant change was noted in the parathyroid glands. Based on these data we concluded that in our model, 1) there was a significant calcium loss in the absence of any change in the serum calcium, but 2) this hypercalciuria alone was not lithogenic, and 3) parathyroid glands showed no discernible secondary morphological changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304312 TI - [Pharmacological experiments in aged rat urinary bladder. I. The responses to acetylcholine, norepinephrine and isoproterenol]. AB - To investigate the etiology of unstable bladder in elderly people, we performed pharmacological experiments using the body of the rat urinary bladder. Responses to acetylcholine, norepinephrine and isoproterenol were examined in vitro in aged rats (16 and 24 months old) in comparison with young rats (6 months old). The results of the present study were summarized as follow: 1) The body weight of 16 and 24 months rats was significantly greater than that of the control. 2) There was no significant difference in the response to acetylcholine among three age groups. 3) The contraction strength of 16- and 24-month-old rat urinary bladder induced by norepinephrine was significantly greater than that of the control. 4) The relaxation response of the detrusor strips induced by isoproterenol in 24 month-old rats was significantly smaller than that of the other two groups. It is concluded that responses to alpha-adrenergic agonists were enhanced in the aged rat urinary bladders. In the assumption that a similar change occurs in the human bladders, the age-related increase in the responsiveness to alpha-adrenergic agonists is one of the etiologies or contributing factors for unstable bladder. PMID- 2304313 TI - [Changes in lanthanum permeability of rat Sertoli cell tight junction after CDDP administration]. AB - Using electron microscope, distribution of lanthanum tracer in the seminiferous epithelium was evaluated in adult male rats 2, 7, 25 and 53 days after single intraperitoneal injection of 3 mg/kg of CDDP. Lanthanum penetrated beyond the tight junction between Sertoli cells and the maximum penetration around the spermatid was found on the 7th day, when any degenerative changes of seminiferous epithelium were not recognized light microscopically. And 4 weeks pretreatment with Cephalantin and Kallikulein had no effects on this lanthanum tracer penetration around the spermatid. On decreasing this lanthanum tracer penetration after 7 days, some lanthanum was also found around the spermatocytes on the 53rd day but not around the spermatid. It is proposed that lanthanum tracer penetration beyond the Sertoli cell tight junction may be a morphological marker of early Sertoli cell dysfunction after CDDP administration. PMID- 2304315 TI - [Clinical experiences of 35 cases with upper urinary tract stones by extracorporeal shock wave lithotripter (MEDSTONE 1000)]. AB - We made clinical trials of the extracorporeal shock wave lithotripter (MEDSTONE 1000) in patients with upper urinary tract stones. Thirty-five cases (total 40 trials) treated during the period of October 1987 through March 1988 were enrolled in this study. The ages of the cases ranged from 22 to 65 (average 43.9) years old, comprising 23 men and 12 women. The site of presence of urinary tract stones was the renal pelvis and calyx in 28 cases and the upper ureter in 7 cases. The size of the stone was smaller than 1 cm in 15 cases, 1 to 2 cm in 12 cases, 2 to 3 cm in 7 cases and larger than 3 cm in 1 case. 13 patients with renal stones were treated with double-J stent catheter and all patients with ureteral stones were treated with the ureteral balloon catheter or flexible-tip ureteral catheter as preoperative manipulation. In 26 cases epidural anesthesia was used and the others were treated under general anesthesia. Stone targetting was determined by two oblique radiographs from separate axes. The intensity of shock waves was mainly 24 KV and the maximum shock wave counts to break up stones were 6800 shots. The size of the broken stone fragments was less than 2 mm in 24 cases (68.5%) and 2 to 5 mm in 10 cases (28.6%), which indicated that the procedure was very effective. However, one case in whom the stone could not be broken was with cystinuria. After three months the fragments completely passed in 22 cases (64.7%) and the residual fragments larger than 5 mm were left in 2 cases (5.9%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304314 TI - [Adrenal regeneration hypertension--effects of vascular connective tissue protein and plasma corticosterone on hypertension in rats with adrenal regeneration hypertension]. AB - In young rats consuming 1% NaCl drinking solution, unilateral nephrectomy and bilateral adrenal enucleation caused a hypertension. Plasma corticosterone concentration in hypertensive rats was not significantly higher than that of normotensive control rats in early hypertensive or chronic hypertensive stage. At the end of experiment, each rat received an intravenous injection of 0.4 microCi/g of 3H-lysine and was sacrificed 2 hours after the injection. Incorporation of 3H-lysine into collagen or elastin of the mesenteric artery and heart in hypertensive rats was greater than that of normotensive rats. Administration of phenoxybenzamine hydrochloride lower the blood pressure of hypertensive rats and reduced the incorporation of 3H-lysine into collagen and elastin of the mesenteric artery and heart. From these findings, increased protein synthesis of collagen and elastin in hypertensive rats appears to play an important role for the maintenance of adrenal regeneration hypertension. PMID- 2304316 TI - [Lower urinary tract function in myelomeningocele. Long-term follow-up data]. AB - We have analyzed long-term follow-up data of the lower urinary tract in 58 myelodysplastic patients. The patients consisted of 16 males and 42 females, whose age varied from 3 months to 16 years old (mean of 7). The follow-up periods ranged from 18 to 100 months (mean of 82). 1. While the bladder compliance of 41 patients conservatively treated with clean intermittent catheterization increased significantly from 5.1 to 11.1 ml/cmH2O, that of 17 patients who underwent anti reflux surgery failed to do so. 2. A significant correlation was observed between bladder deformity and bladder compliance. A severe deformity was encountered more in the patients surgically treated. 3. Uninhibited contractions decreased in magnitude or disappeared in 26 patients, and increased in strength or developed newly in 8. The remaining 24 cases did not demonstrate them at all. 4. The maximum urethral closure pressure changed +/- 20 percent of the initial value in 27 of 38 patients (71%). The mean value tended to fall at 60 cmH2O. PMID- 2304317 TI - [Calcium urolithiasis and bone change]. AB - Bone mineral contents of calcium urolithiasis patients (105 males and 52 females) were measured by the microdensitometry (MD) method, and the patients were divided into the MD normal group and the MD abnormal group. The patients were also divided into the group (21 males and 3 females) treated with thiazides for 1 year or more and the nontreated group to examine various factors in blood and urine. [Nontreated group] The rate of MD abnormality was higher in younger males. The rate tended to increase with age in females. Alkaline phosphatase values were significantly higher in MD abnormal group males than in MD normal group males. Urinary calcium excretion and PTH values were significantly higher in MD abnormal group females than in MD normal group females. Comparison of hypercalciuria and normocalciuria revealed no significant difference between the MD normal rate and the MD abnormal rate. Comparison of single of stone formers and recurrent stone formers also revealed no significant difference between the MD normal rate and the MD abnormal rate. [Treated group] PTH and alkaline phosphatase values were significantly higher in the treated group than in the nontreated group. Alkaline phosphatase values were significantly higher in the MD abnormal group. From the viewpoint of stone recurrence prevention, the monitoring of bones where the majority of calcium in the body is present is considered important besides behavior of calcium in blood and urine. PMID- 2304318 TI - Land snails as experimental animals: a study of the variability and distribution of individual weights in Helix aspersa snails born from the same clutch. AB - A study was carried out to examine the distribution of individual weights in Helix aspersa snails, the aims being to establish the best estimate of the ponderal growth and also to obtain a model growth curve. Four groups of 20 snails from the same clutch were analysed and kept under experimental conditions from birth up to 6 months. The variability of their individual weights within groups was studied by calculating the coefficients of variation every 15 days. At the same time, the assumed normal distribution of those weights was being tested. The coefficients of variation increased with age and the assumed normal distribution of individual weights had to be rejected. By means of a log transformation of the original data, a model growth curve was constructed, and was used to assess the possibility of estimating age from weight. We finally reached the conclusion that median weight, rather than the mean, would be a better measure of central tendency to use until it is possible to obtain selected populations. The difficulty of estimating age from weight is emphasized. PMID- 2304319 TI - A method for perfusion of the isolated rabbit liver through the portal vein and the hepatic artery in a recirculating system. AB - We describe a method for the isolation and recirculating perfusion of rabbit livers. Livers were perfused simultaneously through the portal vein and the hepatic artery. Precise descriptions of the surgical preparation, perfusion apparatus and perfusion method are given. The viability of rabbit livers was assessed with the use of physiological, biochemical and histological parameters. We conclude that the isolated perfused rabbit livers are sufficiently viable to study their short-term metabolism. PMID- 2304320 TI - Computerized ordering of experimental animals and test authorization. AB - The authorization procedure required by law in Switzerland and the internal set up at Roche for acquiring experimental animals has made a computerized system for monitoring authorizations and animal deliveries essential. The INQUIRE software program, which can be run on the central computer, was used to set-up databases with information on all personnel who place orders and perform experiments (PERI), authorization matters (BEWI), orders (ORDR), deliveries (SPED), animal species (SPEC), animal strains (STRE), populations (POPU) and the management of various data (BARA). The authorizations database (BEWI) permits sequential searches on specific questions. The animals ordered in the ORDR database are constantly updated in BEWI, thus ensuring that the authorized animal quotas are not exceeded. Expiry of an authorization or an unregistered experimenter will come to light in the course of the plausibility study. Through ORDR the experimenter has a good overview of the animals that he has ordered or have been ordered for him, and he can select the most appropriate strain or population for his studies in STRE or POPU, which contain data on the genetic and physiological characteristics as well as the breeding and keeping of all sublines and stocks. Realization of the IFIS project has made it a simple matter to keep a check on the legal requirements pertaining to animal experimentation and to update the information and evaluate the entire stock of data at any time. PMID- 2304321 TI - The effect of haemolysis on certain canine serum chemistry parameters. AB - Haemolysis has been known to cause artefacts in certain canine serum chemistry parameters. These parameters are often used by researchers to detect toxicity in certain studies; haemolysis, therefore, can make serum chemistry interpretation very difficult. In order to determine whether a relationship existed between the level of haemolysis and certain canine serum chemistry parameters, haemolysis was artificially induced by adding a haemolysate of known haemoglobin concentration to serum specimens. A routine clinical chemistry profile was performed on each specimen. Statistical analyses were performed on the results to examine the relationship between level of haemolysis and serum chemistry results. Interpretation of serum chemistry results of haemolysed canine sera paralleled, in most cases, human historical data. PMID- 2304322 TI - Seasonal variations in male mice at the time of sexual maturation. AB - The sexual maturation of male mice reared under constant laboratory conditions was studied in animals born in different months of the year. The body weights were significantly affected by the month of birth. Males born in March and May were heavier at 4 and 5 weeks of age than those born in autumn and winter. As indicated by the relative weights of accessory glands, males born in spring matured earlier compared with animals born in other months of the year. Variation in the relative testicular weights during maturation was not influenced by the month of birth. Female mice also showed a significant relationship between the month of birth and sexual maturation. Females born in March reached puberty, as measured by the age of vaginal opening and first oestrus, earlier than those born in other months of the year. PMID- 2304323 TI - Adrenal cortical response in clinically normal dogs before and after adaptation to a housing environment. AB - 58 dogs (29 males and 29 females) selected as healthy on clinical and biochemical evaluations were subjected to an ACTH adrenal function test 2 days after their admission to a veterinary hospital (t + 0). Basal female serum cortisol concentrations were significantly higher than concentrations in males (77 nmol/l versus 43 nmol/l; P less than 0.01). Concentrations post stimulation were not statistically different (P greater than 0.05) between males and females: 306 (+/- 69) nmol/l versus 291 (+/- 73) nmol/l, respectively. Twelve dogs (6 males and 6 females), randomly selected from the 58, were subjected to the same test 5 weeks later (t + 5) and 12 weeks later (t + 12). Basal cortisol concentrations were lower at t + 5 or at t + 12 than at t + 0. Post stimulation mean cortisol concentrations were lower in males than in females at t + 5 (162 versus 232 nmol/l; P less than 0.05) but not at t + 0 (262 versus 320 nmol/l; P greater than 0.05) and t + 12 (188 versus 233 nmol/l; P greater than 0.05). These findings are indicating an increased susceptibility of bitches to environmental stress. PMID- 2304324 TI - A modified technique for the production of an arterio-venous shunt in sheep, allowing a comparison of biocompatibility of synthetic materials. AB - Polytetrafluorethylene (PTFE) prostheses were implanted in 12 sheep as a shunt between the carotid artery and the jugular vein using an end-to-side anastomosis technique. This technique allows repeated tests of the pharmacological and toxicological safety of artificial kidney units after both single and multiple administration. Furthermore, it enables the investigation of detoxification of compounds via dialysis, thus contributing to drug safety. Implantation of the prosthesis was uncomplicated. Connection to the extracorporeal circulation was achieved via catheters and maintained using a pump with an output of up to 300 ml/min. This enabled maintenance of extracorporeal circulation for several hours without clinical impairment to the animals. The AV-shunts remained functional for between 8 and 253 days (mean 112.3 days). PMID- 2304325 TI - Glomerular lipidosis in a Syrian hamster of the APA strain. AB - Spontaneous glomerular lipidosis was found in a 12-week-old male Syrian hamster of the APA strain. Lipids in the glomeruli were observed as droplets in a prominently expanded mesangial area and as emboli in a dilated capillary lumen. Lipid deposition was also, but less often, detected in tubular epithelial cells and interstitial cells around the lipid-laden glomeruli. This case of glomerular lipidosis was considered to be closely related to hyperglycaemia and hyperlipidaemia. PMID- 2304326 TI - Adrenocortical zonation of inbred wild-coloured mastomys, Praomys coucha: a new border zone in the cortex of females. AB - Adrenal glands were examined in the inbred strain of wild-coloured mastomys (Praomys coucha), MWC. The most characteristic findings were emergence of a border zone between the zona fasciculata and z. reticularis of the cortex in females but not in males, and persistence of broad z. reticularis in males. The border zone was typically comprised of vacuolated cell layers, nodular layers and fibrous tissue. Vacuolated cells increased in number during pregnancy and partially disappeared during lactation. Growth of the nodules was greatly enhanced in both number and size during lactation. Thus, multiparae had very thick border zones composed predominantly of large nodules and, additionally, of vacuolated cells and fibrous tissue. The z. reticularis was compressed into a cord of closely packed cells by the expanded border zone in multiparous females but it continued to thicken with age in males. These changes produced completely different cortical zonation in the adrenal between sexes. PMID- 2304327 TI - Mouse strain differences in resident peritoneal cells: a flow cytometric analysis. AB - A flow-cytometric study of resident peritoneal cells among 8 mouse strains showed a more than twofold variation in the ratio of macrophages to macrophages plus lymphocytes, ranging from 27% in A/J to 62% in C57B/L10, with significant strain differences in a number of other cellular parameters. There was a particular deficiency of lymphocytes in strain CBA/N, which carries the xid mutation. Studies of the phagocytosis of fluorescent beads also revealed large differences in the number of beads taken up, ranging from 0.99 per cell in MFI to 1.64 per cell in BALB/c mice in a 20-min period. The total number of peritoneal cells collected also varied between strains, ranging from 2.75 x 10(6) in CBA/Ca to 5.85 x 10(6) in MF1. The total yield of macrophages per mouse ranged from 0.93 x 10(6) in A/J to 3.16 x 10(6) in C57BL/10. These differences should be taken into account when designing experiments which use resident peritoneal cells. PMID- 2304328 TI - Sequential bronchoalveolar lavages by endotracheal intubation in guineapigs. AB - We examined the feasibility of performing repeated bronchoalveolar lavage (BAL) on guineapigs. We also determined the influence of lavage volume on cell recovery in these animals, verified if the free cell populations were altered by repeated lavage, and compared the results with those obtained after euthanasia. Live animals were intubated orotracheally by direct vision laryngoscopy and lavaged, except for the last BAL which was done on isolated lungs after euthanasia. Each animal was lavaged weekly for 8 weeks: weeks 1-5 lavages were done with 5 aliquots of 2 ml of normal saline, week 6 with 3 aliquots of 1 ml, week 7 with 3 aliquots of 2 ml, and week 8 with 5 aliquots of 2 ml after euthanasia. The first 5 BAL gave similar results in volumes recovered, total number of cells, cell viability and differentials. The total cell yield of lavages 6 and 7 was less than that of the first 5 BAL and BAL 8; cell differentials with these smaller lavages were similar except for the percentage of neutrophils which was slightly higher than with the 10 ml lavage at week 3. The final lavage gave similar results as the first 5 BAL in terms of total cells recovered, cell viability, and differentials. We conclude that repeated BAL is feasible in live guineapigs, and that it gives a similar cells yield as lung lavage obtained after euthanasia. PMID- 2304329 TI - T cell autoimmunity in the central nervous system--a new twist at an old rope. PMID- 2304330 TI - IgA nephropathy in alcohol abuse. An animal model. AB - In search of an animal model for alcohol abuse related IgA nephropathy, we investigated the Tsukamoto-French alcoholic rat. Continuous intoxication was induced by gastric infusion of a liquid diet with up to 47% ethanol in Wistar rats designated "alcoholic". Control animals received the same calorie count in the form of glucose. Animals were sacrificed after 6 or 10 weeks. IgA nephropathy was observed in 67% (10 of 15) of alcoholic rats and in none of 14 controls (p less than 0.0002). Alcohol abuse related renal changes, similar to those described in humans were present. These included mild mesangial expansion and intense IgA deposition. Foot process effacement was observed in alcoholic animals; severe proteinuria was found in half the animals with IgA nephropathy. This is the first report of chronic ethanol ingestion induced mesangial IgA nephropathy in an animal model. PMID- 2304331 TI - Cationization of bovine serum albumin alters its conformation as well as its charge. AB - The molecular charge on bovine serum albumin (BSA) was modified by substituting carboxyl groups on the protein with ethylenediamine, thereby producing a highly cationic derivative with a pI of 9.3 to 9.5. Gel-filtration studies showed that the molecular weight of BSA was not significantly altered after cationization. When the cationized BSA was administered to rabbits using a chronic serum sickness schedule of injections, the animals developed a membranous glomerulopathy similar to the human disease, except that approximately one-third of the animals also showed focal and segmental endocapillary proliferation. Comparison of the circular dichroism spectra of native and cationized BSA showed that the substitution of the carboxyl groups resulted in a 50% reduction in the alpha-helical content of the native molecule. This conformational change should be considered as a possible determinant of the different immune response and immunopathology associated with the cationized molecule compared with native BSA. PMID- 2304332 TI - Stability of anticancer activity induced by cellular differentiation. AB - Human and murine cells can express anticancer activity which we define as any biologic process that can prevent or inhibit the expression of the transformed phenotype. The existence of anticancer activities has been demonstrated by many systems, including the fusion of normal cells with tumorigenic cells and the implantation of cancer cells into specific embryonic sites. Furthermore, cellular differentiation has recently been shown to regulate the expression of anticancer activity without limiting a cell's proliferative potential. Those results show that reversible nonterminal differentiation (NTD) induces 3T3T mesenchymal stem cells to become resistant to transformation by physical or chemical carcinogens or oncogene products and NTD induces spontaneously transformed 3T3T cells to revert to a benign state and to become resistant to retransformation. In addition, NTD induces SV40 T-antigen transformed 3T3T cells to revert to a nontransformed state that prevents growth in soft agarose. Data are now presented that define the relative stability of these differentiation-induced anticancer activities. Anticancer activity induced by NTD in 3T3T cells is shown to have a mean stability of 55 population doublings (PD) and a maximum stability of 88 PD. Anticancer activity induced by NTD in spontaneously transformed 3T3T cells shows a similar stability with a mean of 55 PD and a maximum of 95 PD. Finally, in SV40 3T3T cells, the induction of NTD suppresses soft agarose growth for a maximum of 20-30 PD. These results demonstrate that three forms of differentiation-induced anticancer activity are stable for an extended number of population doublings. PMID- 2304333 TI - Heterogeneous subgroups among malignant diffuse small B cell lymphomas. A combined nucleometric and immunocytologic study. AB - The degree of heterogeneity among subtypes was evaluated in 39 of the most frequent malignant, diffusely growing small B cell lymphomas by a combination of morphometry, automated image analysis, and immunocytologic techniques. Cluster analysis of nuclear profile parameters, including nuclear area, circularity factor, and chromatin distribution pattern, distinguished 3 groups. Each group was characterized by the preponderance of certain nuclear profile types, i.e. (a) small, rather regular (roundish) and dark staining (typical small lymphocytic lymphomas and immunocytomas); (b) small to intermediate size, rather regular (roundish) and pale staining (small to intermediate size variant); or (c) small to intermediate size, irregular, rather pale staining (diffuse follicular small cleaved cell (centrocytic) lymphomas and, probably, polymorphous immunocytomas). Group 3 was clearly distinct from the rest, but groups 1 and 2 also differed significantly. Every case displayed a mixture of the 13 registered nuclear profile types. Lymphoid cells with similar nuclear profile features occurred in B cell zones of non-neoplastic lymph nodes. Frequency distribution of nuclear profile parameters significantly differed from one lymphoma group to another. However, there were considerable overlaps. No clear correlation was found between nuclear profile types and immunophenotypes. Cellular surface antigen patterns showed an extensive intra- and inter-case variability. The findings support the notion of a certain individuality of malignant B cell lymphomas and of a marked heterogeneity among their subtypes. PMID- 2304334 TI - Chemical and physiochemical comparison of advanced atherosclerotic lesions of similar size and cholesterol content in cholesterol-fed New Zealand White and Watanabe Heritable Hyperlipidemic rabbits. AB - Watanabe Heritable Hyperlipidemic (WHHL) and cholesterol-fed New Zealand White (CH-FED NZW) rabbits were sacrificed at 15 months of age or after 16 weeks of cholesterol feeding, respectively. During the experimental period, the arterial walls of both the CH-FED NZW and WHHL rabbits were exposed to similar amounts of cholesterol and the lesions which developed at the aortic arch had similar intimal thicknesses, total lipid and cholesterol content. However, the lesions of the WHHL rabbits morphologically resembled human plaques, and contained lipid in the form of smectic liquid crystalline droplets and cholesterol monohydrate crystals. The CH-FED NZW rabbits had lesions which were fatty streak-like, containing liquid crystalline cholesteryl ester droplets but few crystals. The aortic arch intimas of the CH-FED NZW rabbits contained significantly more cholesteryl ester, and less unesterified cholesterol and triglyceride, than those of the WHHL rabbits. The intimal compositions of the two rabbit models did not overlap. Analysis of the compositions predicted precipitation of cholesterol monohydrate crystals in the WHHL but not the CH-FED NZW. The physical state of the deposited cholesterol esters was similar in both with about half being in smectic liquid crystalline form at body temperature. Since the size and total lipid content of the lesions of the CH-FED NZW and WHHL rabbits were similar, we suggest that the greater time of exposure to hypercholesterolemia was important in the formation of cholesterol monohydrate crystal-containing plaques in the aortic arch of the WHHL rabbits. PMID- 2304335 TI - Nuclear deoxyribonucleic acid content (ploidy) of endodermal sinus (yolk sac) tumor. AB - Paraffin sections from 30 endodermal sinus (yolk sac) tumors were Feulgen stained, and nuclear DNA content (ploidy) was assessed through DNA cytophotometry using the microTICAS image analysis system. The series consisted of 20 ovarian, 8 testicular, 1 sacrococcygeal, and 1 mediastinal tumors. Of the 30 endodermal sinus (yolk sac) tumors 29 were shown to be aneuploid, whereas the remaining tumor which exhibited the recently described primitive intestinal or enteric pattern was diploid and may thus be considered a neoplasm showing a somewhat higher degree of differentiation as compared to tumors showing the other histologic patterns of endodermal sinus (yolk sac) tumors. PMID- 2304336 TI - Comparison of two techniques to isolate microvascular endothelial cells from the omentum. AB - The purpose of the study was to compare two different techniques for isolation of omental microvascular endothelial cells (ECs). Segments of unreinforced polytetrafluorethylene (PTFE) grafts, 9 cm long and 6 mm in diameter, were implanted in 22 dogs as an aortic interposition. Fourteen grafts were seeded with a mean of 7 x 10(5) viable ECs, derived from the microvessels of the omentum: eight grafts (group A) were seeded with ECs obtained by collagenase digestion and by filtration through a pore mesh; six grafts (group B) were seeded with ECs obtained by collagenase digestion and by Percoll gradient separation. In eight grafts (group C), the ECs were not added to the preclot mixture and served as a control. Animals were sacrificed 5 weeks after surgery. The percentage of thrombus-free area was 65 +/- 22% for group A grafts and 74 +/- 15% for group B grafts (NS). The subendothelial layer was 280 +/- 60 microns thick in group A and 220 +/- 30 microns thick in group B (P less than 0.05). Seeded grafts showed a higher production of 6-keto-PGF1 alpha after addition of sodium arachidonate than control grafts. Percoll gradient separation allows isolation of a more purified suspension of ECs. Refinements in omental EC procurement are still required to minimize contamination with other types of cells. PMID- 2304337 TI - Identification of human appendicitis by in vitro nuclear magnetic resonance. AB - The spin-lattice relaxation time, T1 as determined by nuclear magnetic resonance techniques, correlates positively with tissue water content. The latter relationship has been observed in rabbits with experimentally induced appendicitis whose inflamed appendiceal tissues had significantly higher T1's and water contents than tissue from normal controls. The present experiment studied these relationships in humans. Tissue water content and T1 were measured on appendiceal tissue from 10 patients with documented appendicitis and from 6 controls without the disease. All T1's were determined within 30-60 min of removal of the appendix at operation. The mean in vitro T1 of appendiceal tissue from patients with appendicitis was significantly higher than that of controls (527 +/- 15 msec versus 430 +/- 17 msec, mean +/- SEM, P less than 0.002). In addition, a strong positive correlation was noted between T1 and tissue water content (r = 0.70, P less than 0.01). Based on these findings, the use of in vivo magnetic resonance imaging techniques to detect human appendicitis noninvasively warrants investigation. PMID- 2304338 TI - An experimental evaluation of the order of revascularization after interrupting hepatic afferent blood flow. AB - The purpose of this study was to investigate the influence of the order of revascularization on hepatic metabolic function after interruption of hepatic afferent blood flow to reconstruct the portal vein and the hepatic artery. Hepatic ischemia was induced in male rabbits by clamping the afferent hepatic blood supply. In the cases in which portal blood flow was released after 15 min of hepatic ischemia and hepatic arterial blood flow was released 15 min later, hepatic metabolic function, which was assessed by arterial ketone body ratio, plasma lactate, and hepatic energy charge levels, recovered immediately. When hepatic arterial blood flow was released in the reverse order, the recovery of hepatic function was delayed. In the cases in which portal and hepatic arterial blood flow were released simultaneously after 30 min of hepatic ischemia, hepatic function did not recover even 180 min after reperfusion. In contrast, the venous bypass was established during portal clamping, restoration of hepatic function was accelerated, and there was no significant difference in restoration between the methods of releasing portal blood flow first or releasing hepatic arterial blood flow first. In the method of simultaneous releasing, however, it was most delayed, probably due to the prolonged ischemic time. These results suggest that releasing first the portal or hepatic arterial blood flow with the establishment of venous bypass during the portal clamping would be the best order of revascularization for hepatic function when reconstructing the portal vein and the hepatic artery. PMID- 2304339 TI - Effect of different fractions of alkaline reflux on the gastric stump and the esophagus: an experimental research on pigs. AB - An experimental study was conducted to evaluate the effect of different fractions (bile and pancreaticoduodenal secretions) on the gastric stump and esophageal mucosa. Twenty pigs underwent partial gastrectomy (two-third distal) and cardiomyotomy in order to induce free gastroesophageal reflux. Then, reconstruction of the alimentary tract was performed to assess the effects of different types of alkaline reflux. A combined (biliary and pancreaticoduodenal) reflux, an isolated biliary reflux, and an isolated pancreaticoduodenal reflux were induced, respectively, in three different groups of five pigs each. In a control group a Roux-en-Y gastrojejunostomy was performed. Nine months later, the animals were sacrificed, the esophagus and the gastric stump were removed for histologic examination. The results show that the most severe histopathological lesions are determined by combined alkaline reflux; on the other hand, separated fractions can induce only mild changes on the gastric stump and esophageal mucosa. PMID- 2304340 TI - Comparison of contact and free beam laser endarterectomy. AB - Free beam laser endarterectomy (LE) and contact laser endarterectomy (CLE) were compared in 15 arteriosclerotic New Zealand white rabbits. The rabbits underwent balloon catheter trauma to the thoracoabdominal aorta and were fed a 2% cholesterol diet for 18 weeks. Thoracoabdominal exploration was performed under general anesthesia and multiple endarterectomies were performed in each rabbit. Atheromas were dissected from arteries with laser radiation and end points were welded in place with laser radiation. LEs (N = 8) were performed with argon ion radiation delivered through a 400 microns fiberoptic. Power was kept constant at 1 W and the average fluence was 97.5 +/- 6.6 J/cm2. CLEs were performed with conical sapphire probes powered by either argon ion radiation (N = 12) or Nd-YAG radiation (N = 10). Power used was 1 W to 4 W for each laser. Average argon ion fluence was 117.8 +/- 3.1 J/cm2 and average Nd-YAG fluence was 611.1 +/- 34.4 J/cm2. Following the operations, aortas were removed, fixed, serially sectioned, and stained. Microscopic study revealed welded end points with LE but not with CLE. There were no perforations with LE. There were 11/12 perforations with argon ion CLE and 8/10 perforations with Nd-YAG CLE. Free beam laser endarterectomy is superior to contact laser endarterectomy for experimental atheromas. PMID- 2304341 TI - Immunomodulation of vascular endothelium. 1. Ultrastructural changes following ultraviolet B irradiation of peripheral veins. AB - Immunologic function of endothelial cells is especially important in consideration of vein allografting for arterial reconstruction and in organ allotransplantation. Ultraviolet B radiation (UVB) has previously been shown to modulate graft immunogenicity, and to alter cell surface receptor function. In this study, superficial epigastric veins were UVB irradiated with 10, 24, 40, 80, and 150 mJ/cm2 while control veins were not irradiated; all specimens were examined for endothelial ultrastructural changes. Veins were perfuse-fixed at 1, 3, 7, 14, and 28 days after irradiation, and were evaluated by transmission electron microscopy and scanning electron microscopy. Control veins had a normal appearing endothelial lining, composed of elongated, attenuated endothelial cells. Veins irradiated with more than 24 mJ/cm2 displayed injured endothelial cells characterized by altered microvilli, defects in the cell surface, and a change in cell shape. The degree of cell damage correlated closely with increasing UVB dose. At doses of 80 mJ/cm2 or greater there was moderate to severe endothelial cell separation from the underlying basement membrane and an increase in cellular lysosomes. The effects of UVB were maximal at 3 days with virtual recovery in resurfacing of all specimens with endothelium 28 days after irradiation. These data suggest that UVB has a dose-dependent effect on venous endothelium that is morphologically reversible with time. Cell membrane changes seen following exposure to UVB may contribute to altered cell surface receptor function. PMID- 2304342 TI - Improved survival in intestinal ischemia by allopurinol not related to xanthine oxidase inhibition. AB - Allopurinol, a xanthine-oxidase (XO) inhibitor, has been used to improve the resistance to ischemia with disappointing results that have been attributed to administration regimen of the drug. Our aim was to investigate the effect of different administration schedules of allopurinol on the survival in rats undergoing intestinal ischemia testing the blockade of XO. Intestinal ischemia was achieved by 90 min of clamping the superior mesenteric artery (SMA) close to its origin from the aorta. Three groups of animals were evaluated: A-group: only the allopurinol solvent was given; B-group: the full dose of allopurinol (100 mg/k b.w.) was given iv and C-group: the 75% dose was administered orally 24 hr before and the remaining 25% was administered 30 min before. Survival was evaluated at 48 hr and the blockade of XO was assayed by High Efficacy Liquid Chromatography (HELC) in homogenate of intestinal wall. Survival was only improved in the C-group (P = 0.02). Levels of hypoxanthine were significantly increased both in B-group and C-group (P = 0.003) when compared with the A-group. Levels of uric acid in B-group (P = 0.0003) and C-group (P = 0.0009) were significantly decreased with respect to A-group. That means that an effective blockade of XO is achieved whichever the regimen of administration. Allopurinol and oxypurinol levels were significantly increased (P = 0.05 and P = 0.008) in C group when compared with B-group. We conclude that the protective effect of allopurinol on survival in intestinal ischemia in rats is not related to the blockade of XO but rather to the allopurinol and oxypurinol levels in intestinal wall. PMID- 2304343 TI - Occurrence of intestinal metaplasia of the stomach in Thai patients with gastritis, benign ulcer, and gastric cancer. AB - Pathological sections of gastrectomized specimens of 74 patients with benign gastric ulcer and 79 with gastric cancer were reviewed. Intestinal metaplasia was found in 26 specimens with benign ulcer (35.1%) and in 43 with cancer (54.4%), a difference that is statistically significant. Further analysis of age groups showed that rate of occurrence of metaplasia in cancer patients older than 60 years was 70.3%, which was significantly higher than that of their younger counterparts (40.5%) and of patients with benign ulcer of either age group. A survey was also conducted by taking biopsies of mucosa of antrum and body of the stomach of 250 patients who underwent gastroscopic examinations. Acute and chronic gastritis was found in 22 and 156 patients, respectively. Intestinal metaplasia was found to be associated with acute gastritis in 2 (9.1%) and with chronic gastritis in 25 (16%) patients. In conclusion, intestinal metaplasia was associated with higher proportion than it was with benign gastric ulcer and gastritis among Thai patients. PMID- 2304344 TI - Absence of effect of supplemental oral calcium on ornithine decarboxylase (ODC) activity in colonic mucosae of healthy individuals with a family history of colorectal cancer. AB - Tissue activity levels of ornithine decarboxylase (ODC) have been suggested to be a marker of colonic epithelial cell proliferation and risk for colorectal cancer. Supplemental dietary calcium has been hypothesized and reported to suppress colonic epithelial-cell proliferation. We measured sigmoid and rectal mucosal ODC activity levels in 45 healthy, disease-free subjects with strong family histories of colorectal cancer before and after 2 months, during which daily dietary supplementation with calcium carbonate (to provide 600 mg calcium base) was taken. Although the mean ODC activity levels decreased in both sigmoid and rectal specimens, these changes were small in relation to the standard deviation and were not statistically significant. These data suggest that the magnitude of dietary calcium intake does not significantly influence sigmoid-rectal mucosal ODC activity levels and that ODC measurements may not be a useful intermediate endpoint for interventions designed to interrupt the colon carcinogenic sequence. PMID- 2304345 TI - Intralesional cis-diamminedichloroplatinum and purified collagen treatment of human metastatic malignancies: a feasibility study. AB - A feasibility study of the treatment of advanced superficial human malignant tumors utilizing direct intralesional injections of cisplatin mixed with purified bovine collagen was performed. The purpose of using intralesional injection of cisplatin mixed with collagen was to limit the drug exposure to normal tissues while increasing the dose and duration of exposure to the tumor. Fourteen evaluable superficial tumors in four patients (melanoma, breast CA, squamous CA from larynx) received a total of 65 treatments in the outpatient clinic setting. All patients had failed prior treatment with systemic intravenous cisplatin. Lesions were treated at least three times at two-week intervals. After intramuscular meperidine premedication, multiple injections of cisplatin mixed with collagen were made into the tumors. There was minimal normal tissue toxicity and minimal systemic toxicity. Tumor regression or stabilization occurred in 86% (12/14) of tumors; 50% (7/14) of lesions regressed more than 50% in size. This study suggests that intralesional colloidal cisplatin can overcome resistance to systemic intravenous cisplatin. PMID- 2304346 TI - Postmastectomy locally recurrent breast cancer. AB - With the popularity of breast-conserving treatment plans, the natural history of "breast recurrence" in the ipsilateral breast must be distinguished from local recurrence following modified radical mastectomy. Hence, this study considers those patients who develop skin or chest wall recurrence after modified radical mastectomy, whether as a primary procedure or for patients with "breast recurrence" after partial mastectomy. The incidence of postmastectomy locally recurrent breast cancer following modified radical mastectomy (MRM) and adjuvant immunotherapy (IT) is compared to historical controls. The risk factors and treatment of local recurrence in this program as well as in a larger group of patients who recurred after modified radical mastectomy are reported. PMID- 2304347 TI - Adriamycin cellular transport: methodological aspects. AB - A rapid and simple method for determination of cellular uptake of adriamycin is described. The method is based on the principle that active uptake is proportional to alterations of drug distribution, measured as a fraction of time, between suspending medium and cells, the volume of each having been accurately determined. Cellular drug uptake can be calculated by the use of a simple distribution formula. This method represents a compromise between indirect measurement of the loss of drug from suspending medium and direct measurement of drug uptake following cell separation, washing, and lysis. This method should be applicable to the measurement of cellular uptake of a wide range of drugs. PMID- 2304348 TI - Model of bronchial hyperreactivity after active anaphylactic shock in conscious guinea pigs. AB - A model of bronchial hyperreactivity at various times after an active anaphylactic shock in conscious guinea pigs is described. The bronchial inflammation was quantified in parallel by determination of the number of mononuclear cells, neutrophils, and eosinophils in bronchoalveolar lavage (BAL) fluids. The guinea pigs were sensitized by an intramuscular (i.m.) injection of a large dose of ovalbumin in Freund's complete adjuvant. The administration of ovalbumin (to induce anaphylactic shock) and of histamine to investigate bronchial hyperreactivity was by aerosol. The bronchial hyperreactivity to histamine was observed 3-6 hr after the anaphylactic shock. In the BAL fluid a decrease (1-3 hr) and then an increase (24-48 hr) in the number of mononuclear cells was found as well as an increase in neutrophils (3-48 hr) and in eosinophils (6-48 hr). The hyperreactivity was not correlated with changes in one category of cell in the BAL fluid. This model constitutes one simple test for investigating bronchial hyperreactivity in conscious guinea pigs. Further work is needed to try to determine the possible inflammatory parameters responsible for the hyperreactivity. PMID- 2304349 TI - High-performance liquid chromatographic analysis of catecholamines in biological samples by liquid/liquid extraction prepurification. AB - A prepurification procedure for the determination of catecholamines in biological samples was studied to simplify the procedure and increase selectivity and recovery. The procedure is based on liquid/liquid extraction of catecholamine borate complexes. Under optimal conditions, catecholamines formed complexes with diphenylborate in an alkaline NH4Cl/NH4OH buffer that were extracted with n heptanol. Catecholamines were reextracted into an HCl-acidified solution, followed by reversed-phase ion-pair high-performance liquid chromatographic separation with fluorometric detection. Application of the method to various samples of rat tissues and human urine showed procedural simplicity, high selectivity, and high recovery (about 90% or more for tissue samples). This method can be used for pharmacological studies on catecholamines. PMID- 2304350 TI - Low volume perfusion-superfusion system for measurement of transmitter release from blood vessels in vitro. AB - An in vitro technique has been developed for the simultaneous recording of vasoconstriction and transmitter release from small perfused blood vessels. To avoid excessive dilution of the released substances, 6-12-mg segments of rabbit ear arteries or rat tail arteries were mounted in 0.5-mL tissue chambers and perfused-superfused in a closed system. Drug administration and removal were performed by timer-controlled solenoid valves. Oscillation in the baseline generated by the roller pump was dampened by delivering Kreb's solution through a 4-mL buffer vial filled partly with air. Vasoconstriction was elicited by electrical stimulation and detected by pressure sensitive transducers. Transducer generated electrical signals were amplified, digitalized, and recorded by a computerized system. Release of norepinephrine was measured after the tissue was preloaded with [3H]norepinephrine. This system allowed us to measure minimum vasoconstrictions of 1-2 mm Hg and [3H]norepinephrine efflux evoked by 4-8 electrical pulses. There was a good linear correlation (r = 0.98) between the contractile responses and tritiated norepinephrine release. Endogenous norepinephrine released by electrical stimulation into the perfusion media was determined by high-performance liquid chromatography (HPLC) in the low picogram range (80-100 pg). Our novel experimental setup permits computerized data acquisition and automated in vitro pharmacological experiments on isolated blood vessels. PMID- 2304351 TI - New analgesic assay utilizing trypsin-induced hyperalgesia in the hind limb of the rat. AB - Subplantar injection of 250 micrograms of trypsin in the rat resulted in a biphasic increase in pain sensitivity (hyperalgesia) with peaks at 10 and 150 min separated by a period of decreased sensitivity to pain (hypoalgesia). Hyperalgesia was assessed by a decrease in response latency to a 3.0-kg force applied to the injected hind limb. Response latencies at 150 min were increased in a dose-dependent manner by pretreatment at 90 min with acetaminophen; phenacetin; the arachidonate cyclooxygenase inhibitors aspirin, indomethacin, and ibuprofen; and the opiate analgesics codeine and morphine. ED50s of 17, 13, 10, 0.48, 1.6, 3.9 and 1.2 mg/kg p.o. were obtained for these drugs, respectively. The hyperalgesia present at 150 min was not affected by pretreatment with antiinflammatory steroids, an antihistaminic, an antiserotonin agent, and an anticholinergic. We recommend measurement of drug-induced increase in response latencies produced 150 min after injection of 250 micrograms of trypsin as the basis for a new sensitive and selective analgesic assay. ED50s obtained in this assay correlate well with doses that are used clinically to produce analgesia. Development of the hypoalgesic component was selectively inhibited by pretreatment with an antiserotonin agent. Additional drug studies indicated that the algesic response to the subplantar injection of trypsin is the resultant of independent, temporally overlapping hyperalgesic and hypoalgesic components. PMID- 2304352 TI - Cultured neurons for testing antihypoxic drug effects. AB - Cultured neurons of chick embryo cerebral hemispheres were used as an in vitro system for investigating the influence of several drugs on neuronal cell viability and metabolic activity under hypoxic conditions. Hypoxia was induced by addition of sodium cyanide to the nutrient medium, which led to a rapid depletion of energy stores. The ATP level of the cells and the protein content of the cultures were used to characterize the degree of neuronal damage after cytotoxic hypoxia and recovery, respectively, recovery lasting 15 min or 3 days. Various calcium antagonists, NMDA-antagonists, central depressants, central stimulants, nootropics, and miscellaneous drugs were tested. NMDA-antagonists and central depressants consistently protected the neurons against alterations caused by hypoxia. However, only one (flunarizine) out of five calcium antagonists, two (naftidrofuryl, pyritinol) out of 13 nootropics, the kappa-agonist ketazocine, and the ATPase inhibitor ouabaine exerted neuroprotection. The in vitro model seems to be suitable for testing neuroprotective drug effects and to be a valuable supplement for in vivo experiments, especially when the cellular mechanism of drug action has to be clarified. PMID- 2304353 TI - An improved method for bonding heparin to intravascular cannulae. AB - The patency of chronically implanted intravascular cannulae is usually limited by thrombus formation at the cannula tip. In the present experiments, methods of improving the antithrombotic properties of the cannulae have been examined using a number of different heparin-bonding treatments. These treatments were evaluated by determining cannula patency in the thoracic aorta of a chronically cannulated rat preparation. Cannulae treated with a heparin-bonding procedure remained patent longer than untreated cannulae. Cannulae treated with tridodecylmethylammonium chloride-heparin-glutaraldehyde remained patent longest (mean patency, 13.3 days compared with 4.0 days in rats with untreated cannulae). This technique provides a simple and effective method of improving the antithrombotic properties of intravascular cannulae by bonding heparin to the lumenal and extralumenal surfaces. PMID- 2304354 TI - Expression of the multidrug resistance gene in myeloid leukemias. AB - The human multidrug-resistance gene (MDR1) encodes an energy-dependent multidrug efflux protein responsible for the cross-resistance of cultured cells to natural product chemotherapeutic agents such as the anthracyclines and vinca alkaloids. RNA transcript levels were measured in leukemia cells obtained from 15 adult acute nonlymphocytic leukemia (ANLL) cases and 15 cases of chronic myelogenous leukemia (CML). Expression of MDR1 RNA was common in ANLL, and appears to be most frequent in leukemic cells of patients with the poorest response to chemotherapy. Expression of the MDR1 gene was not detectable in the peripheral white blood cells of any of the CML cases during the chronic phase, but was detectable in the immature cells present during this phase of the disease. The cells of the three blastic crisis patients contained detectable levels of MDR1 RNA. These studies support the idea that expression of the MDR1 gene contributes to drug resistance in ANLL, and may play a role in some instances in the drug-resistance of CML in blastic crisis. In contrast, studies of the level of expression of anionic glutathione transferase and DNA polymerase B failed to show any relationship between the RNA transcript levels of these enzymes and responsiveness to chemotherapy. PMID- 2304356 TI - Bone marrow cultures and prognosis in primary myelodysplastic syndromes. AB - Bone marrow cultures and survival time were studied in 39 patients with primary myelodysplastic syndromes. We divided the patients into two groups according to the CFU-GM numbers on day 10: type I with low colony (CFU-GM less than 30) and type II with normal to high colony formation (CFU-GM greater than or equal to 30). The median survival time was shorter for patients with an in vitro growth type II (5 months) than it was for patients with an in vitro growth type I (greater than 36 months). No relations was found between growth types and FAB type, Bournemouth score or initial karyotype. The initial bone marrow blast percentage correlated well with the in vitro growth number. PMID- 2304355 TI - Thymidine kinase in human leukemia--expression of three isoenzyme variants in six patients with chronic myelocytic leukemia. AB - In six patients with untreated, chronic myelocytic leukemia (CML), the dominating thymidine kinase (TK) activity was compared with the fetal form, TK 1, from mitogen stimulated and the adult form TK 2 from unstimulated normal human lymphocytes, and with TK-1-onc, TK-3-onc and TK-4-onc. This was done in human acute, myelocytic and monocytic leukemias, using the combined thymidine/dTTP enzyme kinetics for isoenzyme characterization. TK-1-onc was found in one, TK-2 onc in two and TK-3-onc in three CML patients. The suffix -onc indicates the difference in ATP kinetics and molecular weights between the normal and the leukemic thymidine kinases. A possible relation between the isoenzyme forms and the types of leukemias is discussed. PMID- 2304357 TI - De novo Ph negative T-cell lymphoblastic leukaemia associated with bcr gene rearrangement. AB - One case of de novo Ph-negative T-cell acute lymphoblastic leukaemia has been found to have a classical breakpoint cluster region (bcr) rearrangement of the type seen in chronic granulocytic leukaemia. There were no haematological features to suggest a previous chronic phase. This case represents the first report of this rearrangement in Ph negative acute T-lymphoblastic leukaemia at presentation. The implications for various therapeutic options in such patients are discussed. PMID- 2304358 TI - Molecular diversity of precursor B acute lymphoblastic leukemias identified by the immunoglobulin heavy chain gene organization. AB - Acute leukemias with morphological, cytochemical, and immunological characteristics correlating to precursor B lymphocyte and with germ line configuration of immunoglobulin heavy (IgH) chain loci were studied for the organization of antigen receptor genes including C mu, Ig light (IgL) chain, T cell receptor (TCR) beta and gamma. Three of the five lymphoblast samples retained the germ line configuration of both Ig JH and C mu region. The other two samples showed deletion of the entire JH region resulting in the rearrangement of the C mu region. None of these five cases had a Ig L chain gene rearrangement. The three cases with germ line IgJH and C mu loci were revealed to belong to stage I (HLA DR+), stage II (HLADR+, CD19+), and stage III (HLADR+, CD19+, CD10+) B precursor ALLs, respectively. The two cases with deletion of IgJH region also belonged to stage II and III B precursor ALL. Thus immunologically classified stage II and III B precursor ALLs include those with germ line IgH region, representing ALLs at a very early stage of B cell development. A subgroup of B precursor ALL with deleted IgJH region, which is abortive at the molecular genetic level, was also identified. Karyotype abnormalities involving chromosomal region 11q23 in the leukemias with germ line IgH region are also discussed. PMID- 2304359 TI - Staging of patients with Hodgkin's disease: what should be done? AB - An overview of the place and use of diagnostic investigations necessary for staging of patients with Hodgkin's disease is given. Staging followed by specific treatment according to stage remains the corner stone in the management. New imaging techniques such as computed tomography and ultrasound cannot completely replace lymphangiography. Staging laparotomy should not be used routinely in clinical stage I and II patients. In the past, staging laparotomy was performed to identify those patients for whom management decisions would depend on the identification of abdominal disease. However, with the identification of prognostic factors and the subsequently selected therapy-regimens including treatment of possible spleen involvement, the role of laparotomy in patients management has largely decreased. PMID- 2304360 TI - Presenting features and treatment outcome of adolescents with acute lymphoblastic leukemia. AB - Adolescents had lower rates of remission induction and shorter event-free survival than younger children in this study of consecutively treated patients with acute lymphoblastic leukemia (ALL). When compared to the younger patients (ages 1-9 years; n = 995), adolescents (ages 10-21 years; n = 338) were significantly more likely to have adverse prognostic features, including T cell phenotype, L2 blast cell morphology, higher serum lactate dehydrogenase level, higher leukocyte count, leukemic cell DNA index less than 1.16, and ploidy other than hyperdiploidy greater than 50. Within the adolescent group, outcome was worse for those older than 15 years. The increased frequency of unfavorable clinical and biologic features undoubtedly accounts in part for the poorer prognosis of adolescents with ALL. However, the independent prognostic significance of age greater than or equal to 10 years suggests that as yet unknown factors contribute to treatment failure in adolescent patients. PMID- 2304361 TI - Cellular ara-CTP pharmacokinetics, response, and karyotype in newly diagnosed acute myelogenous leukemia. AB - We evaluated relationships between ara-CTP pharmacokinetics in myeloblasts, response, and karyotype in 147 patients with newly diagnosed AML treated on three protocols each initiated by a 3 g/m2 ara-C dose given over 2 h. Area under the curve of ara-CTP concentration times time (AUC) or peak ara-CTP concentration after this dose did not predict response or response duration, suggesting that inability to form ara-CTP is an unlikely mechanism of ara-C resistance. Following high-dose bolus ara-C therapy patients with INV [16] or del [16q] had long remissions despite low AUC and peak values while patients with -5, del [5q], -7, or del [7q] were frequently resistant despite average AUC and peak values. In 55 patients treated with high-dose continuous infusion ara-C as a single agent, steady-state ara-CTP concentrations were significantly lower in resistant patients (who again were disproportionately those with -5, del [5q], -7, or del [7q]) although there was no correlation with CR duration. PMID- 2304362 TI - Clinical implications of the histopathologic diagnosis of pulmonary lymphomatoid granulomatosis. AB - We reviewed the epidemiologic, laboratory, roentgenographic, pulmonary function, and survival data from 28 patients who had a histologic diagnosis of lymphomatoid granulomatosis (LG) with involvement of the lungs. The mean age at the time of diagnosis was 51 years, and the male-to-female ratio was 3:2. Ten patients had other underlying diseases before LG was diagnosed. The most prominent symptoms were cough, dyspnea, fever, and rash, which were usually present for several months before diagnosis of LG. Multiple nodules were detected on a chest roentgenogram in 68% of the patients. Immunoglobulin concentrations were abnormal in 8 of 12 patients studied. Although bronchoscopy established the diagnosis in approximately a third of the patients who underwent this procedure, open-lung biopsy was uniformly diagnostic. The median survival was 72 months, with follow up through 12 years. In 11 patients, the original diagnosis of LG was eventually changed to lymphoma. In five of these patients, the change in diagnosis was based on immunohistologic data obtained shortly after LG was discovered. Lymphoma diagnosed in this way was associated with a better prognosis than lymphoma diagnosed on the basis of conventional histopathologic findings. In three patients, solid tumors eventually developed. The diversity of clinical outcomes and frequent revisions of the diagnosis led us to consider the possibility that LG may also represent a histopathologic finding that occurs transiently in several disease processes. PMID- 2304364 TI - Symposium on myocardial ischemia--Part I. Proceedings. PMID- 2304363 TI - Does Helicobacter pylori colonize the gastric mucosa of Meckel's diverticulum? AB - Helicobacter pylori (formerly, Campylobacter pylori) is a highly adapted organism that seems to infect only gastric-type mucosa. In this study, we attempted to determine whether gastric epithelium at a site distant from the stomach, the heterotopic gastric mucosa of Meckel's diverticulum, was susceptible to colonization by H. pylori. Retrospectively, we examined biopsy specimens from 23 patients who had undergone resection of Meckel's diverticulum that contained heterotopic gastric mucosa. As a methodologic control, we also reviewed antral biopsy specimens from 18 patients with chronic duodenal ulcer who had undergone antrectomy. Heterotopic gastric mucosa in Meckel's diverticulum was of antral type in 13 patients and fundic type in 10 patients. Six patients had an ulcer in the diverticulum. No evidence of chronic or active chronic gastritis was detected in the heterotopic gastric mucosa. H. pylori was not found in any Meckel's diverticula but was present in the antrum of 89% of patients with duodenal ulcer. These results suggest that H. pylori may not colonize the heterotopic gastric mucosa of Meckel's diverticulum and has no role in the development of ulceration at this site. PMID- 2304365 TI - Malignant peripheral nerve sheath tumors of the skin. PMID- 2304366 TI - Ethanol alters vasoactive intestinal peptide-induced steroid release from immature rat ovaries in vitro. AB - The present study was conducted to examine the acute effects of ethanol (ETOH) on basal and VIP-induced release of testosterone (T) and estradiol (E2) from immature ovaries in vitro. Ovaries were collected from anestrus (A) and both naturally occurring and pregnant mare's serum gonadotropin (PMSG)-induced early proestrus (EP) animals. The ovaries were incubated in either media alone, media plus 1 microM VIP, media plus ETOH in doses ranging from 25 to 100 mM, or media plus each dose of ETOH containing VIP. The present results demonstrate that ETOH did not affect either basal or VIP-induced steroid release from ovaries collected from A animals. Likewise, the ETOH did not alter basal steroid secretion from EP animals; however, the drug significantly reduced the VIP-stimulated release of both T and E2 from EP ovaries. Thus, these data demonstrate for the first time that ETOH is capable of altering prepubertal ovarian responsiveness to VIP, a peptide known to be involved in the developmental regulation of ovarian function. PMID- 2304367 TI - In vivo ethanol elimination in man, monkey and rat: a lack of relationship between the ethanol metabolism and the hepatic activities of alcohol and aldehyde dehydrogenases. AB - The in vivo ethanol elimination in human subjects, monkeys and rats was investigated after an oral ethanol dosage. After 0.4 g. ethanol/kg of body weight, ethanol elimination was much slower in human subjects than in monkeys. In order to detect a rise in monkey plasma ethanol concentrations as early as observed in human subjects, ethanol had to be administered at a dose of 3 g/kg body weight. Ethanol metabolism in rats was also much faster than in human subjects. However, human liver showed higher alcohol dehydrogenase activity and higher low Km aldehyde dehydrogenase activity than rat liver. Thus, our data suggest a lack of relationship between hepatic ethanol-metabolizing activities and the in vivo ethanol elimination rate. PMID- 2304368 TI - Rapid non-enzymatic HPLC determination of total MHPG in human plasma. AB - We have previously reported a method for the determination of total 3-methoxy-4 hydroxy phenylethylene glycol (MHPG) in brain, based on a simple acid-catalyzed hydrolysis. Now we extend this procedure to the determination of plasma total MHPG. The method involves the deproteinization of plasma with perchloric acid, followed by 3 minutes of an acid-catalyzed step. The hydrolysates are injected into the HPLC system, using a formic acid/methanol eluent with fluorimetric detection. Sample detection limit is below 1 ng MHPG/mL of plasma. This procedure has been used for the determination of plasma total MHPG from 109 healthy individuals of both sexes. Mean value was: 5.4 + 2.3 ng total MHPG/mL of plasma (means +/- S.D., N = 109). No sex differences were observed, and a slight correlation with age (r = 0.24, p less than 0.02) has been found. Plasma-free MHPG was also determined in a subgroup of 15 randomly chosen individuals (3.0 +/- 1.2 ng free MHPG/mL plasma, means +/- S.D.). A significant correlation was obtained with plasma total MHPG (r = 0.77, p less than 0.001, N = 15). The main advantage of the present method lays in its simplicity, since no enzymatic hydrolysis or extraction procedures are needed, being its reliability fully proven through 109 plasma total MHPG determinations. PMID- 2304369 TI - Serotonin in human lumbar cerebrospinal fluid: a reassessment. AB - An inter-laboratory comparison study was carried out in order to ascertain mean levels of serotonin (5-HT) in human lumbar cerebrospinal fluid (CSF). Analyses were performed using high performance liquid chromatography (HPLC) coupled with either electrochemical (LC-EC) or fluorometric (LC-F) detection. With the detection limits obtained (7-8 pg/ml for LC-EC, 7-15 pg/ml for LC-F) 5-HT was not usually detected in human lumbar CSF. The findings indicate that the true mean concentration of CSF 5-HT is less than 10 pg/ml. This upper limit is substantially lower than all previous reports of 5-HT concentrations in normal human lumbar CSF. The extremely low concentrations of 5-HT present in CSF make it unlikely that CSF 5-HT will be of clinical utility in assessing central serotonergic function. PMID- 2304370 TI - Effect of luteotrophic hormone (LH) and thymosin on mitogen-induced blast transformation of Balb/c mouse lymphoid cells. AB - The present study investigates the effect of a pituitary hormone (LH) and a thymic factor (Thymosin Fraction 5 = TF5) on in vitro and in vivo spleen cell proliferative response of 2, 6 and 8-month-old Balb/c mice. In vitro experiments showed that the addition of LH at various concentrations (0.5, 5, 50 or 500 ng/ml) to cultures increased significantly the proliferative response to some known mitogens (ConA, PHA, PWM). The LH stimulation was further enhanced by subsequent addition of TF5 to these cultures. However, the addition of LH to LPS cultures resulted in a blockage of the cell growth which persisted after the addition of TF5. In vivo experiments showed that injection of LH (5 or 50 ng/ml) to 2, 6 and 8-month-old Balb/c mice had a significant increase on blast transformation of lymphoid cells following their incubation with ConA, PHA and PWM, and a significant decrease when they were incubated with LPS. The physiological significance of these findings which point out an intimate connection between immune and endocrine functions is discussed. PMID- 2304371 TI - Comparison of the effect of lorglumide on pancreatic growth stimulated by camostate in rat and hamster. AB - We conducted a 14 day experiment in which we administered camostate (a trypsin inhibitor) and cholecystokinin alone or in combination with lorglumide, a cholecystokinin receptor antagonist, to both rats and hamsters. Plasma cholecystokinin levels were 21.7 +/- 3.2 pM and 19.6 +/- 2.5 pM with camostate, 16.3 +/- 2.4 pM and 14.8 +/- 2.2 pM with exogenous cholecystokinin, and 3.7 +/- 0.4 pM and 4.2 +/- 1.0 pM in control experiments in rats and hamsters, respectively. Both cholecystokinin and camostate were found to promote pancreatic growth in rats (18 +/- 4 and 111 +/- 7%, respectively) and hamsters (76 +/- 18 and 61 +/- 12%, respectively). Although lorglumide caused a decrease of this effect of camostate in both rats (78 +/- 5%) and hamsters (25 +/- 10%), it only became significant in rats. We therefore conclude that there are important interspecies differences in the role cholecystokinin plays in mediating the trophic effects of trypsin inhibitors on the pancreas. PMID- 2304372 TI - Neuropeptides in brain: effects of microwave irradiation and decapitation. AB - Substance P (SP)-, neurokinin A (NKA)-, neurotensin (NT)-, neuropeptide Y (NPY)- and vasoactive intestinal polypeptide (VIP)-like immunoreactivity (Ll) were measured and characterized by specific radioimmunoassays (RIA) and reverse phase high performance liquid chromatography (HPLC) in extracts of rat brain. Concentrations of SP-Ll, NKA-Ll and NT-Ll in brains of decapitated animals were 59, 49 and 64 percent lower compared to those found in animals sacrificed by focused microwave irradiation (MW). In contrast, no difference in brain NPY-Ll and VIP-Ll levels was found between animals killed by MW and decapitation. HPLC chromatograms of SP-, NKA-, NT- and NPY-Ll showed the same immunoreactive components in extracts of brains from both groups of animals. Thus, no additional immunoreactive components were formed by MW compared to those found after decapitation. The present findings may reflect an MW-induced inhibition of peptidase activity or, perhaps, a more efficient extraction of certain neuropeptides following MW treatment. The results imply that the traditional methods of sacrifice may result in the measurement of spuriously low tissue concentrations of some peptides, e.g. tachykinins, in brain. PMID- 2304373 TI - Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. AB - Microdialysis in the human brain has been performed for the first time during thalamotomy intended to relieve tremor in patients with Parkinson's disease. The aim was to test the reliability of the microdialysis technique for biochemical characterization of a target area in the human brain during a routine operation. Microdialysis probes were introduced through the same trajectory as the lesioning electrode thus causing no additional damage to the brain. Dopamine, DOPAC, HVA, 5 HIAA, hypoxanthine, inosine, guanosine, adenosine, GABA, taurine, aspartate and glutamate were measured in the perfusate from the target region - the Vim nucleus. The results show initial high levels that reach baseline levels after 10 20 minutes. Surprisingly, consistent and reproducible levels were found, the only exception being one patient on 1-DOPA therapy who had elevated DA and metabolite levels. PMID- 2304374 TI - The constitutive 7-ethoxycoumarin 0-deethylase of human placental microsomes: relationship to the intermediary steps in steroid aromatization. AB - All oxidative functions of aromatase, i.e., estrogen production, 19-oxygenated androgen production and 7-ethoxycoumarin deethylation, were inhibited in parallel in placental microsomes from non-smokers by the mechanism-based, time-dependent inactivators (suicide substrates) 10 beta-(2-propynyl)estr-4-ene-3,17-dione and 4 hydroxyandrost-4-ene-3,17-dione. In contrast, the aromatase suicide substrate androst-4-ene-3,6,17-trione had little or no effect on the conversion of androst 4-ene-3,17-dione to 19-hydroxyandrost-4-ene-3,17-dione or on the conversion of the latter to 3,17-dioxoandrost-4-en-19-al while severely limiting the capacity for estrogen production from androst-4-ene-3,17-dione and 19-hydroxyandrost-4-ene 3,17-dione in such microsomal preparations. Androst-4-ene-3,6,17-trione, therefore, appears to uncouple the 19-hydroxylation of androgens from estrogen synthesis. This agent also produced only a minimal inhibition of 7-ethoxycoumarin deethylation, indicating that this major constitutive transformation of a xenobiotic chemical is associated with the steroid 19-hydroxylating function of the aromatase system. PMID- 2304375 TI - Intrathecal pertussis toxin attenuates the morphine withdrawal syndrome in normal but not in arthritic rats. AB - The effect of intrathecal pertussis toxin on morphine dependence was studied in rats suffering from chronic pain (Freund's adjuvant-induced arthritis). Animals were rendered tolerant-dependent by subcutaneous implantation of 3 pellets of 75 mg morphine base each. In both, normal and arthritic animals, 1 microgram pertussis toxin reduced the analgesia induced by morphine in the tail-flick test. Naloxone (1 mg/kg, s.c.) precipitated a withdrawal syndrome in arthritic animals that was milder in respect to the one produced in normal rats. Pretreatment with pertussis toxin significantly diminished the incidence of withdrawal signs such as jumps, squeak on touch, chattering, ptosis, body shakes and diarrhoea in tolerant-dependent normal rats, while this effect could not be observed in animals suffering from chronic pain. This differential activity of the toxin could be due to the altered tonus of certain neurotransmitter systems that accompanies the chronic situation of pain. PMID- 2304376 TI - Simultaneous measurement of tetrahydrobiopterin (THBP) and biogenic amines by liquid chromatography with electrochemical detection. AB - This report describes a rapid and sensitive method for measuring tetrahydrobiopterin (THBP) and biogenic amines simultaneously by liquid chromatography with electrochemical detection (LC-ECD). The coefficient of variation for THBP was 4.87% and the minimum detectable amount of THBP was approximately 20 pg. These results indicate that this simple reverse-phase ion pair chromatography system can be used for the simultaneous analysis of endogenous THBP and biogenic amines without long sample preparation time. PMID- 2304377 TI - Structure-neurotoxicity trends of analogues of 1-methyl-4-phenylpyridinium (MPP+), the cytotoxic metabolite of the dopaminergic neurotoxin MPTP. AB - The dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) derives from its metabolism to 1-methyl-4-phenyl-pyridinium cation (MPP+), which is then selectively accumulated in dopaminergic neurons. In an effort to assess the structural requirements governing MPP+ cytotoxicity, we evaluated dopaminergic toxicity of MPP+ analogues 3 weeks after their microinfusion into rat substantia nigra. We also evaluated the substrate suitability of MPP+ analogues for high-affinity dopamine uptake in striatal synaptosomes by measuring their ability to induce specific dopamine release. The intranigral neurotoxicity of MPP+ analogues in vivo correlates mainly with their in vitro inhibitory activity on mitochondrial respiration, consistent with a compromise in cellular energy production as the principal mechanism of MPTP-induced cell death. This study extends the structure-neurotoxicity data base beyond that obtainable using MPTP analogues, since many of these are not metabolized to pyridinium compounds. Such information is crucial to assess which possible endogenous or exogenous compounds may exert MPTP/MPP(+)-like toxicity. PMID- 2304378 TI - Reduction of T-kininogen messenger RNA levels by dexamethasone in the adjuvant treated rat. AB - When inflammation is induced in rats following injection of Freund's complete adjuvant, steady state levels of T-I and T-II kininogen mRNAs increase markedly as do plasma levels of T-I and T-II kininogens. When rats are additionally treated with dexamethasone, T-I and T-II steady state mRNA levels and plasma levels of T-kininogens are reduced. The results suggest that dexamethasone may affect the magnitude of T-kininogen gene induction caused by inflammation. PMID- 2304379 TI - Direct cardiovascular actions of two metabolites of linoleic acid. AB - Two newly discovered oxidation products of linoleic acid (i.e., 9,10-epoxy-12 octadecenoate termed Leukotoxin A, and 12,13-epoxy-9-octadecenoate termed Leukotoxin B) are produced by neutrophils in a variety of species. These substances appear to combat bacterial infection although they also have detrimental effects on normal organ function. Administration of Leukotoxin A or B to isolated cat papillary muscles decreased developed force, an index of myocardial contractility, in a concentration-dependent manner. Leukotoxin B was more active in decreasing the developed force than Leukotoxin A at high concentrations. Leukotoxin A or B, when added to isolated perfused cat carotid arteries, produced a significant vasoconstriction which in vivo would result in an increased vascular resistance. Thus, leukotoxins exert significant direct effects on the cardiovascular system in cats. Leukotoxins A and B are both cardiodepressant and vasoactive independent of release of other blood borne mediators. PMID- 2304380 TI - Antagonism of presynaptic dopamine receptors by phenothiazine drug metabolites. AB - Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors. PMID- 2304381 TI - Comparative disposition of adriamycin delivered via magnetic albumin microspheres in presence and absence of magnetic field in rats. AB - The multiple tissue disposition of adriamycin hydrochloride delivered via magnetic albumin microspheres, in absence (control) and presence of magnetic field (experimental), has been investigated in rats. The animal tail was demarcated into three segments: T1, the dosing-site; T2, the target-site; and T3, the post target-site. Following the arterial cannulation at T1, 0.4 mg/kg of microsphere associated drug was administered to the control as well as the experimental animals. In experimental group, the target-site T2 was exposed to a 8000 G magnetic field for 30 min. In both groups the animals were sacrificed in triplicates over a 48 hr period and their various tissues monitored for drug concentrations using HPLC. In presence of magnetic field, the microspheres demonstrated 16 fold increase in the maximum drug concentration, 6 fold increase in drug exposure and 6 fold increase in the drug targeting efficiency for T2. Drug delivery to most non-target tissues, including heart and liver, was substantially reduced. The results quantitatively suggest that the efficacy of magnetic albumin microspheres in the targeted delivery of incorporated therapeutic agent is predominantly due to the magnetic effects, and not alone due to the characteristics of the micro-carrier system. PMID- 2304382 TI - The products of the mdr1a and mdr1b genes from multidrug resistant murine cells have similar degradation rates. AB - Two vinblastine-resistant sublines of the murine macrophage-like cell line J774.2, J7.V1-1 and J7.V3-1, overproduce unique forms of P-glycoprotein that are encoded by distinct mdr genes, mdr1b and mdr1a, respectively. Degradation rates of the two P-glycoprotein isoforms were measured by immunoprecipitation of P glycoprotein. The half-life of immunoprecipitable P-glycoprotein from J7.V1-1 cells was 16.8 +/- 0.5 hours and from J7.V3-1 cells, 17.4 +/- 0.5 hours. This rate was not influenced by the presence of vinblastine in the growth medium. The data indicate that P-glycoproteins derived from distinct genes have similar degradation rates. PMID- 2304383 TI - Random sampling by glitter drop method. AB - In the course of a study on glioblastoma tissue and cultured cell lines, a glitter drop technique for random sampling was introduced (1). Here, we report the initial description of the details of this procedure and its application to cell counts from explant slides and to determining bromodeoxyuridine (BUdR) labeling indices (LI) in tissues. The method is without bias, easy to perform and takes only a short time. It compares well with three other generally used random sampling procedures. PMID- 2304384 TI - Asymmetric synthesis and teratogenic activity of (R)- and (S)-2-ethylhexanoic acid, a metabolite of the plasticizer di-(2-ethylhexyl)phthalate. AB - The stereoselectivity of the teratogenic activity of 2-ethylhexanoic acid (EHXA), a metabolite of the widely-used plasticizer di-(2-ethylhexyl)phthalate, was investigated. The enantiomers of EHXA were prepared via asymmetric synthesis with the aid of the chiral auxiliaries (R)- and (S)-1-amino-2 (methoxymethyl)pyrrolidine (RAMP, SAMP). The aqueous solutions of the sodium salts of (R)- and (S)-EHXA and the racemic EHXA [+/- )-EHXA) were injected each morning and evening of day 7 and 8 of gestation in the NMRI mouse (500 mg/kg, i.p.), a period highly sensitive in regard to the production of neural tube defects (exencephaly) by branched-chain carboxylic acids. (S)-EHXA did not yield any teratogenic or embryotoxic response in this model, while (R)-EHXA was highly teratogenic (59% of living fetuses exhibited exencephaly) and embryotoxic (as indicated by embryolethality and fetal weight retardation); the exencephaly rate induced by (+/- )-EHXA was between those of the two enantiomeres (32%). It is therefore likely that stereoselective interactions of the enantiomers of EHXA with chiral molecules in the embryo are decisive in regard to the teratogenic response. This first example of the stereoselectivity of the teratological activity of an environmental pollutant suggests that the safety of man-made chemicals can be improved by the use of pure enantiomers instead of racemates. PMID- 2304385 TI - Tolerance to diazepam and methyl-beta-carboline-3-carboxylate measured in substantia nigra of benzodiazepine tolerant rats. AB - The spontaneous activity of neurons in the pars reticulata of substantia nigra (SNpr) was studied in chloral hydrate anesthetized rats. As a function of dose, intravenous diazepam decreased, and methyl-beta-carboline-3-carboxylate (beta CCM) increased discharge frequency. Two days after terminating a one week treatment with flurazepam (FZP), both diazepam and beta CCM showed decreased ability to alter SNpr neuronal activity. Neither residual FZP nor down-regulation of benzodiazepine receptors can account for these results. In contrast, behavioral testing revealed no change in the ability of i.v. beta CCM to cause convulsions, suggesting that sites other than the SNpr are of prime importance in expressing the convulsant actions of systemically injected beta CCM. PMID- 2304386 TI - AIDS--living long and living well: an idea whose time has come. PMID- 2304387 TI - Pediatric AIDS care in Maryland. PMID- 2304388 TI - The emerging physician-patient partnership. PMID- 2304389 TI - Exceptional patients live long and live well. PMID- 2304390 TI - Another look at the data. PMID- 2304391 TI - Mortality following release from prison. AB - We have studied deaths occurring after release from prison in the Canton of Geneva during the period 1982-86. The mortality rate during the first year after release was about 5 deaths/1000 person years, a rate over four times the age adjusted rate in the general population. The majority of deaths were due to overdose by opiate drugs among young, frequently imprisoned drug abusers, and occurred within the first few weeks after release. Likely risk factors include loss of tolerance to opiates while in prison, and psychological and social stresses following release. PMID- 2304392 TI - Compulsory hospital admissions: dangerous decisions? AB - The criterion of dangerousness as a justification for compulsory hospital admission remains pervasive in current British legislation. This study focuses on the actual use of the dangerousness criterion since the 1983 Mental Health Act. A consecutive series of 53 compulsory admissions to the Academic Unit, All Saints Hospital, Birmingham, England was studied. The investigation suggests that, despite the great debates on the dangerousness issue recently, there has been little, if any, shift in the way that psychiatrists use the concept of dangerousness in assessing persons for compulsory admissions. The results echo the earlier work of Bean (1980). Dangerousness is not the primary issue of concern in terms of compulsory admission. The present study suggests however that psychiatrists are not making dangerousness assessments in a stereotypical manner. PMID- 2304393 TI - Pulmonary vascular occlusive disease presenting as sudden death. AB - We report a case of pulmonary vascular occlusive disease (also termed pulmonary veno occlusive disease) which caused the sudden death of an eleven-year-old girl. The post-mortem findings are described and the current theories of aetiology and pathogenesis of this unusual condition are reviewed. The clinical picture is characterized by pulmonary hypertension with marked increase of pulmonary arterial pressure but often normal or only slightly elevated wedge pressure. The pulmonary vasculature, especially the veins, show progressive fibrotic occlusion. The aetiology is unknown but an infective cause is considered most likely. Definitive diagnosis usually depends on an open lung biopsy or, more commonly, autopsy examination. PMID- 2304394 TI - A study on the correlation of blood and vitreous humour alcohol levels in the late absorption and elimination phases. AB - By using the urine:blood alcohol level ratio as the indicator, the correlation of blood alcohol level (B) and vitreous humour alcohol level (V) in the late absorption and elimination phases was studied. It was found to be good (r = 0.98) and B = 0.76V + 4.7. It is suggested that this equation can safely be used to estimate the minimum blood alcohol level where cadaveric blood is unsuitable or unavailable for analysis and that the B/V ratio can be used to infer the phase in which death occurred where urine is not available. PMID- 2304395 TI - The pitfalls which may be encountered during an examination for signs of sexual abuse. PMID- 2304396 TI - Is the victim blameless? AB - The study concerned 50 cases occurring throughout Austria between 1950 and 1962 where murder was committed for the purpose of robbing the victim. Fifty-nine convicted killers and 61 victims were involved and 1950 was chosen as the starting point of the research in order to avoid undue influence from the extraordinary factors affecting criminality during and immediately following the Second World War. Cases were consecutive and unselected apart from a very small number excluded through unavailability of their files for legal reasons at the time when the data were collected. Unsuccessful murder attempts were not excluded since there is no difference between crimes actually carried out and those merely attempted as regards criminogenic factors, the pre-criminal situation, the choice of victim, the relationship and interaction between criminal and victim, and the recourse to homicide. However, the inquiry was confined to cases where guilt had been proven because of the aim to study not only the crime and the victim, but also the relationship of the criminal and victim. The latter is obviously not possible where the murderer remains unknown. Accordingly, since the material comprises a large number of cases over a fairly long period (more than a decade) from all over Austria, it is fair to claim that it provides an overview of the criminality of murder with intent to rob, and of the killers and the victims, for an entire country and over a significant epoch. PMID- 2304397 TI - Psychopathic disorder--a useful clinical concept? AB - The study reported upon here set out to investigate the degree to which the clinical concept of psychopathic disorder was shared between psychiatrists, psychologists and probation officers. Despite the small sample of respondents, it seems not unreasonable to conclude from the results reported below that the diagnosis of psychopathic disorder is still considered to be a useful one. PMID- 2304398 TI - Dangerous patients. Third party safety and psychiatrists' duties--walking the Tarasoff tightrope. PMID- 2304399 TI - Factors affecting a fatal outcome in road accidents. AB - The North Report mentioned the question of whether charges and/or sentencing should be modified by fatal outcome following offences involving bad driving. This note classifies factors relating to the accident, the casualty and medical care which may, often fortuitously, determine a fatal outcome. It is suggested that these should be borne in mind in deciding offences and sentencing. PMID- 2304400 TI - The evolution of the American test for the admissibility of scientific evidence. AB - Most legal systems, including the British, have adopted a flexible, liberal standard for admitting scientific evidence. Although these systems consider the novelty of a scientific theory as a factor in evaluating the reliability of the scientific evidence, they do not follow a rigid rule excluding scientific testimony based on new theories and techniques. In the United States, however, most jurisdictions follow a rule automatically rejecting testimony based on novel scientific techniques. Reformers have severely criticized that rule, and the American courts now seem to be moving towards the British position on the admissibility of scientific evidence. PMID- 2304401 TI - On the interpretation of maggot evidence in forensic cases. PMID- 2304402 TI - Medico-legal problems of ischaemic heart disease and myocardial infarction. AB - The medicolegal importance of ischaemic heart disease and myocardial infarction is summarized and discussed. Some theories of pathogenesis and aetiology of ischaemic heart disease, specially those which are more important and relevant to the medicolegal practice, are discussed. Results of the study of 33 cases of coronary artery atherosclerosis and myocardial infarction at different stages of development are presented. The condition of the coronary arteries and the myocardium is examined on gross and microscopical levels. Pathological findings are correlated with the clinical data obtained from the case histories and the summaries of the necropsy requests. No good correlation exists between the observed pathological changes and the clinical age of the infarction and, in most instances, the latter appears younger than the age estimated on the pathological ground alone. As far as the age of the infarction is concerned, most special histochemical staining methods are not preferable to the routine haematoxylin and eosin method. However, the former are efficient in demonstrating and confirming certain aspects of the infarction which cannot be ascertained by the latter method of staining. Pathological alterations associated with myocardial infarction at successive ages are explained and various methods of estimating the time of the infarction are discussed. Thus, gross and microscopical appearances of the acute, organizing and healed myocardial infarction are illustrated by photographs and the forensic applications of these morphological changes are discussed. Lastly, a rare case of an acute myocardial infarction associated with a heat stroke is presented and the medicolegal problems resulting from this case are discussed. PMID- 2304403 TI - Legal system and forensic science. PMID- 2304404 TI - Alcohol in drink driving swabs: does it make any difference? PMID- 2304405 TI - Differential responses to proprioceptive neuromuscular facilitation (PNF) stretch techniques. AB - The purpose of this study was to investigate the effects of sustained stretch and two common proprioceptive neuromuscular facilitation (PNF) stretch techniques on hamstring muscle activation and knee extension range of motion (ROM) in different athletic populations. Three stretch techniques: stretch-relax (SR), contract relax (CR), and agonist contract-relax (ACR) were applied to 10 endurance athletes (EN), 10 high intensity athletes (HI), and 10 control subjects (C). The results revealed that ACR produced 89-110% greater hamstring EMG activity (P less than 0.05) and 9-13% more knee joint ROM than CR and SR, respectively. This same pattern was evident for the individual subject groups. Comparisons of mean data among the three subject groups revealed that the EN athletes generated 58-113% more hamstring EMG activity (P less than 0.05) than the HI and C groups, respectively, across all stretch conditions, whereas the EN group attained significantly less ROM than the HI and C groups for CR and ACR conditions. It was postulated that high intensity-short term activity training necessitates less hamstring resistance to knee extension than long term endurance training. The findings suggest that decreases in muscle activity may not be strongly related to increases in joint range of motion and that factors other than muscle relaxation are important in achieving increased ROM. Also, the differential effects of various stretch techniques between dissimilar athletic populations should be considered if stretch-induced injury is to be avoided. PMID- 2304406 TI - The effectiveness of weight-belts during the squat exercise. AB - The purpose of this study was to examine the effectiveness of weight-belts during the performance of the parallel squat exercise. Six subjects were filmed (40 fps) as they performed three trials at each of three belt conditions (NB, none; LB, light; HB, heavy) in random order and three load conditions (70, 80, 90% 1RM (one repetition maximum] in increasing order. The parameters examined were collected and interfaced to a computer via an analog-to-digital (A/D) converter: ground reaction forces, intra-abdominal pressure (IAP), and EMG for the rectus abdominus (RA), external oblique (EO), and erector spinae (ES) muscles. Most differences were observed during the 90% 1RM condition, and only they are presented in this paper. Maximum IAP values were always greater (P less than 0.05) for the weight belt conditions (LB, 29.2; HB, 29.1 greater th an NB, 26,8 kPa). Similar results were observed for the mean IAP. The integrated EMG (iEMG) activity of the muscles and adjusted mean values for back compressive force and back muscle force followed a similar but opposite pattern, with NB being the greatest. ES mEMG/(L5/S1) values for HB (18.1%) were the least, followed by LB (20.01%) and NB (22.3%). Few differences were observed between belt types. These data suggest that a weight-belt can aid in supporting the trunk by increasing IAP. PMID- 2304407 TI - Responses of aerobically fit men and women to uphill/downhill walking and slow jogging. AB - Few studies have thoroughly examined metabolic, cardiovascular, and psychophysiological responses to negative treadmill (TM) exercise. We compared oxygen consumption (VO2), heart rate (HR), and perceived exertion (RPE, 0-10 Borg scale) during incremental TM exercise featuring both downhill and uphill stages. Subjects were aerobically trained males (N = 12, VO2max = 61 ml.kg-1.min-1) and females (N = 12, VO2max = 53 ml.kg-1.min-1). On separate occasions, each subject walked (4.8 kph) or jogged (9.6 kph) for 25 min. Five minutes were spent at each of five grades (-10, -5, 0, 5, 10%, or the reverse). TM speed and percent progressions were randomized. VO2 and HR did not differ in the 4.8 kph condition when TM grade was negative. During 9.6 kph, both VO2 and HR significantly (P less than 0.001) increased with progressive increments, but increases were less when TM grade was negative. RPE did not differ in the 4.8 kph condition except at 10% grade, where responses were significantly (P less than 0.001) higher. In 9.6 kph, RPE responses were significantly (P less than 0.001) greater during positive stages. The only gender effect occurred at 10% in the 9.6 kph condition, where women had greater (P less than 0.01) RPE responses than men. Results suggest that both walking and jogging economies differ between negative and positive TM grades. Gender differences appear negligible when comparing aerobically trained men and women. PMID- 2304408 TI - Interpreting the relationship between age of menarche and prepubertal training. AB - It has been concluded from studies using retrospective data and thus quasi experimental designs that menarche may be delayed by prepubertal athletic training. Furthermore, a causal relationship between the age of initiation of training (AIT) and the age of menarche (AOM) has been proposed. To investigate the possibility that these conclusions were erroneous and based upon analytical artifact, a computer program was used to generate random and independent AOM and AIT for a population of 30,000 "athletes". The generated mean AOM (means = 13.4 yr) and mean AIT (means = 10.0 yr) were similar to those reported in recent literature. The sampling procedure was designed such that no relationship existed between AOM and AIT in these hypothetical athletes (r = 0.002). When two subgroups (pre- or post-menarcheal training) were compared, the pre-training group was found to have a significantly later AOM than the post-trained group (means = 13.9 yr vs means = 11.7 yr; P less than 0.05). Significant correlations were found for each subgroup between AOM and AIT (r = 0.46 and 0.40 pre- and post menarcheal training, respectively), similar to values previously reported. In conclusion, the sampling procedures performed in the present study and in similar data sets result in biased estimates of the statistical parameters. This bias accounts for the reported relationship between AOM and AIT derived using this type of quasi-experimental design, and therefore it would appear appropriate to state that the age of menarche in athletes is "later" rather than "delayed". PMID- 2304409 TI - The body as a bioenergetic system--lessons from systems engineering and comparative physiology. AB - This introductory review considers some concepts of energy supply and demand from the perspective of a systems engineer looking at comparative physiology. The non steady-state response of oxygen uptake shows major differences between animal species. Similarly, maximal oxygen uptake shows between-species differences. It is suggested that the systems engineering approach could help in understanding questions concerning the interrelationship of these observations. PMID- 2304410 TI - Variables, constants, and parameters: clarifying the system structure. AB - This paper introduces the terminology and application of parameter estimation techniques for clarifying models of pulmonary gas-exchange control dynamics. Results are given of modeled first-order systems, and the extension of such models to higher orders is discussed with examples. It is emphasized that justification of the adequacy of a model is statistically quantifiable and must be performed before appropriate interpretation of system behavior is possible. PMID- 2304411 TI - Trials and tribulations of intervention research. PMID- 2304412 TI - [Additional information]. PMID- 2304413 TI - [Tremor. Possibilities and limits of drug therapy]. PMID- 2304414 TI - [Pharmacotherapy of acute cerebral infarct]. PMID- 2304415 TI - [Drug administration. Liquid drugs for peroral administration]. PMID- 2304416 TI - [Prostaglandin E2 and D2: opponents in the regulation of the sleep-wake rhythm?]. PMID- 2304417 TI - Treatment of pressure ulcers. PMID- 2304418 TI - Viral-associated hemophagocytic syndrome. PMID- 2304419 TI - Neuropsychologic and CT examinations in leukemic patients surviving 10 or more years. AB - Long-term survivors of childhood leukemia were studied to determine their neuropsychologic status. All had had cranial irradiation 10 or more years before. The results were 1. The IQ and academic performance of 56 cured leukemic patients show no significant difference from the normal population. 2. More exact neuropsychological tests (attention, reaction time, visual-motor coordination, memory) reveal important deficits. 3. The frequency of CT aberrations in 33 study patients was 45% and showed no correlation with either the IQ or other neuropsychological results. PMID- 2304420 TI - Familial phaeochromocytoma: successful treatment with 131I-MIBG. AB - We report the case of a family in which the mother died of hypertensive encephalopathy following the relapse of a phaeochromocytoma. Two of her children are still alive. Both children had malignant phaeochromocytomas that have been treated by surgery and 131I-MIBG. The first child presented with phaeochromocytoma of the right suprarenal gland at the age of 7 years. Surgery was performed. At the age of 14 years, he developed a tumour of the left suprarenal gland and two pulmonary metastases demonstrated by 131I-MIBG. The three tumours were removed, but new lesions occurred. The boy then was treated with 200 mCi (7,400 MBq) of 131I-MIBG given twice, and is now free of disease more than 2 years after treatment. His sister presented at the age of 12 years with phaeochromocytoma of the left suprarenal gland, the only lesion recognized by 131I-MIBG. The tumour was removed, but 5 months later, she developed phaeochromocytoma in the right suprarenal gland. She was treated with 200 mCi (7,400 MBq) of 131I-MIBG and surgery was performed 6 months later. Histology of the suprarenal gland could not demonstrate the persistence of phaeochromocytoma cells. The child is now free of disease more than 2 years after treatment. PMID- 2304421 TI - Intracellular ribonucleotide pools of lymphoblastic leukemic cells in untreated and relapsed ALL children. AB - Intracellular ribonucleotide pools were analyzed by HPLC with leukemic blasts obtained from 20 children, including 13 untreated ALL, 5 relapsed ALL, and 2 lymphomas with hematological relapse. Nucleotide pools were, in general, found more expanded among relapsed cases. Also, the larger mono and diphosphate ribonucleotide levels found in relapsed cells, for instance adenine nucleotide pools, were significantly larger among the relapsed patients, as measured 216.97 +/- 53.30 nmol/10(8) cells, in contrast to 109.70 +/- 39.54 nmol/10(8) cells with untreated children (p less than 0.005). Furthermore, AMP and ADP occupied only 18% of the total adenine pool in untreated children, but 34% in relapsed children. The similar pattern of nucleotide pools was observed in guanine, cytidine, and uridine nucleotide pools. Inosine mono phosphates were measured 5.07 +/- 6.02 nmol/10(8) cells with untreated ALL, and 3.55 +/- 1.44 nmol/10(8) cells with relapsed ALL, but thymidine mono phosphates, as a key pyrimidine nucleotide of salvage pathway, were larger (p less than 0.01) among with relapsed patients measuring 31.47 +/- 8.11 nmol/10(8) cells as compared with that of untreated ALL, 11.19 +/- 12.84 nmol/10(8) cells. The present results may suggest that there is a difference in nucleotide metabolism between untreated and relapsed leukemic cells, and nucleotide profiles provide more accurate information of leukemia chemotherapy. PMID- 2304423 TI - Sudden neurologic death after intrathecal methotrexate. AB - Methotrexate leukoencephalopathy is a chronic syndrome of ataxia and confusion which may progress to seizures, coma, and death. We report a fatal case of this syndrome in a patient who displayed no evidence of the typical prodrome of neurologic symptoms or signs. This patient suffered brain death after receiving 11 doses of intrathecal methotrexate for leukemic meningitis. Since leukoencephalopathy was not clinically suspected, this case underscores the need for a test that would reliably monitor central nervous system toxicity due to intrathecal therapy. PMID- 2304424 TI - Systemic Castleman's disease in association with Evan's syndrome and vitiligo. AB - Systemic Castleman's disease is a lymphoproliferative disorder which has been associated with autoimmune phenomena. We report a case of the plasma cell variant of Castleman's disease that was associated with autoimmune hemolytic anemia and autoimmune thrombocytopenia (Evan's syndrome), and vitiligo, the association of which has not been previously reported. PMID- 2304422 TI - Pharmacokinetics of cytosine arabinoside in cerebrospinal fluid and of its metabolite in leukemic cells. AB - Concentrations of ara-CTP in leukemic cells isolated from CSF and of ara-C in lumbar CSF were measured following intraventricular ara-C administration in two girls with refractory meningeal leukemia. CSF samples were collected with a permanent intrathecal-lumbar catheter. In contrast to the comparatively short retention of ara-C in the CSF (t1/2 1.8 to 2.9 hours), there was a high accumulation and an extremely long retention of ara-CTP in the leukemic cells (t1/2 8.1 to 36 hours). The patients included in this study had an ara-C resistant disease. No obvious relationship was seen between concentrations of ara C in the CSF and of ara-CTP in the leukemic cells. Similar studies were performed after simultaneous intraventricular administration of hydrocortison and ara-C. Hydrocortison did not increase ara-CTP retention in the leukemic cells, nor did it effect CSF pleocytosis. PMID- 2304425 TI - Cytotoxic drug-induced fever: a report on procarbazine-induced hyperpyrexia. AB - A case of hyperpyrexia induced by procarbazine in a child with Hodgkin's disease, neurofibromatosis, and pectus excavatum deformity is presented. After the diagnosis of stage IIIS Hodgkin's disease, combined COPP chemotherapy was initiated. One week later she presented with high fever. After a diagnosis of infection was made, chemotherapy was stopped and antibiotics were given. Nearly the same picture recurred three times after reinstituting chemotherapy. On the fourth occasion, the patient had to be hospitalized because of hyperpyrexia and arrhythmia. There was no obvious reason for fever, and cytotoxic-induced fever was considered. The drugs were given one at a time. When a test dose (10 mg) of procarbazine was given, she developed a high fever with severe nausea and vomiting. The reaction was controlled by antihistaminics and steroids. To our knowledge this is the second report on hyperpyrexia due to procarbazine administration. PMID- 2304426 TI - Radiation therapy in the management of Langerhans cell histiocytosis. AB - Twenty-two patients with Langerhans cell histiocytosis (LCH) were managed in the UCLA Department of Radiation Oncology from 1974 to 1987. Their median age was 17 years (range 1-42 years) and median followup 4.5 years (range 1-13 years). Fourteen patients had disease localized to a bone (13) or a soft tissue (one). Eight patients had LCH involving multiple bones (3) or soft tissues plus bones (5). Nine of 10 patients less than 19 years old had disease confined to bone(s) compared to 7 of 12 older patients. Fifty-six sites of LCH (40 bone, 16 soft tissue) were irradiated. Pediatric patients received therapy to 15 sites (14 bone, 1 soft tissue) and adults 41 sites (26 bone, 15 soft tissue). Median dose for bone lesions was 900 cGy (range 600-1,500) and for soft tissue 1,500 cGy (range 600-2,600). Local control was achieved in 46 of 56 sites (82%). Control rates for bone and soft tissue lesions were 35 of 40 (88%) and 11 of 16 (69%), respectively. Fifteen of 15 sites in pediatric patients were controlled compared to 29 of 41 (72%) in adults. Ten sites (18%) recurred 10 months to 4 years after irradiation. Recurrences were in-field and noted only in adults with involvement of multiple soft tissues plus bones. All recurrent soft tissue lesions had been treated with orthovoltage. Five patients developed new foci of LCH subsequent to irradiation. Four of these patients had disease involving soft tissues and bones. One patient with progressive LCH initially presented with a single bone lesion. The acute and chronic effects of radiation therapy were minimal. One patient suffered transient enlargement of adenopathy. An elevated serum TSH level was detected 9 years after irradiation of a cervical vertebra in another patient. PMID- 2304427 TI - Can we achieve 'health for all' by 'putting patients first'? PMID- 2304428 TI - Research utilisation in practice. AB - A small working group was set up in Wales to examine the extent to which nurses use research findings in their day to day clinical work. The group members acted as facilitators to their colleagues exploring with them the problems and issues affecting research utilisation in practice. A number of criteria are discussed which are necessary to encourage change and develop a critical approach to practice. Suggestions are also made for ways in which professional nursing may be developed within the overall context of future educational and management changes. PMID- 2304429 TI - Development of the nurse tutor's attitude subscale: a pilot study. AB - This study attempts to develop an instrument to measure a nurse-tutor's attitude toward teacher-pupil relationship. The Nurse Tutor's Attitude Subscale comprised of 37 items was adapted from the Minnesota Teacher Attitude Inventory. Although sample size of this survey was too small to allow confident generalisation, the author wishes to share her experience and problems in developing an instrument for measuring teaching attitude of a nurse-tutor in Hong Kong. It is also hoped that through this preliminary communication, more awareness and attention be directed to helping the nurse-tutors to understand that their classroom attitudes affect effectiveness of their teaching and, henceforth, student learning. PMID- 2304430 TI - The Moot Court in teaching bioethics. AB - The first part of this paper describes the nature of a Moot Court (or Mock Trial) and how it has been used in recent years as a teaching method for students in medicine and nursing at the Memorial University of Newfoundland. A whole day is spent in the enactment of an imaginary court case in which issues in bioethics are raised. Civil and criminal cases are used in alternate years. A considerable degree of realism is maintained except for the occasions when the presiding judge needs to make comments to the students in order to explain what is going on. The realism is helped by the fact that the roles of judge and of legal counsel are played by members of the judiciary and lawyers from the Newfoundland bar. In the second part of the paper there is a discussion of the principal issue that arose in the 1988 Moot Court, namely informed consent. In the third part the secondary legal and moral issues that arose are described and in the fourth part there is a discussion of the interface between law and morality that is illustrated by the issues that came up in the Moot Court. PMID- 2304431 TI - Conscience and courage--a critical examination of professional conduct. AB - The roots of professional power and authority lie in the claim to a specific kind of knowledge, the 'knowledge that' and the 'knowledge how'. These kinds of knowledge are included in the notion of 'science'. 'Knowledge why'- the justification for a professional action - demands a moral argument in terms of what is known and can be done (taking 'scientific' knowledge into account) but most importantly asking whether it ought to be done. It is important to ask how a nurse acquires the 'knowledge why' and thereby the means to justify his/her conduct in moral terms. This paper considers the norms of professional conduct, the professional mandate and the determination of what is, to the best of the professional's knowledge and conscience, the right act. The question is raised whether an appeal to the individual conscience can be a reliable guide to a morally justifiable action. An exploration of moral perceptions, moral reasoning and moral argument needs to be part of a professional education which requires a certain kind of courage on part of both teachers and students. PMID- 2304432 TI - The 'high-risk' nursing student: identifying the characteristics and learning style preferences. AB - Declining enrollment has heightened the awareness of nurse educators to the importance of a heterogenous pool of nursing students. The purpose of this study was to identify the learning style preferences and other characteristics of 50 nursing students who were defined as high-risk for academic difficulty in the baccalaureate nursing program. Based on the findings from the study, implications are drawn and a sample of instructional activities outlined. PMID- 2304433 TI - The perception of Swedish nurses and nurse teachers of the integration of theory with nursing practice. An explorative qualitative study. AB - Nursing education in Sweden has undergone quite a few changes during the last decade. The aim has been to make nursing more holistic, individualised and health oriented. Social competence, systematic problem solving and research have also been emphasised. These changes in nursing education have led to new demands on nurse teachers. Nurse teachers, directors of nursing education at three nursing schools and a few nurses were interviewed about the problems they experienced in relation to the new demands. The main problems reported were: 1) students inadequately prepared for nursing education, 2) students' attitudes to the social and health-oriented content of the first course at nursing school, 3) integration of research and nursing, 4) resistance to a more theory-based and nurse teacher dominated nursing education, 5) integration of nursing theory and nursing practice and 6) incompatible demands on the clinical nurse teacher. PMID- 2304434 TI - Cardiopulmonary resuscitation--a teaching guide. AB - As a teacher working in an acute area--Accident and Emergency, I have been concerned for some time about the teaching input on the curriculum for cardiopulmonary resuscitation. In my experience, the students are given a short lecture on the procedure for calling an arrest team in the introductory unit and this is followed by a more in-depth lecture in their final year prior to commencing their clinical allocation on an acute unit such as accident and emergency or intensive care. I have found this to be inadequate as students are, in their own opinion, highly stressed by the thought of dealing with an arrest situation and the skills they demonstrate in their third year are, in my opinion, also inadequate. In my own hospital, we are fortunate to be one of the few centres which train the general public in how to deal with arrest situations in the home or work environment. I, am a trainer on this programme and have successfully argued for a similar programme to be incorporated into the introductory unit of the students' course. What has become clear is that other teachers are equally unnerved by the thought of a cardiac arrest and willingly admit to being inefficient at the actual resuscitation procedure. As a result, I have written teaching guidelines which should help those less experienced at cardiopulmonary resuscitation and will provide them with the necessary information which can be passed on to students. PMID- 2304435 TI - Facilitating peer group teaching within nurse education. AB - Nurse teachers have an obligation to explore every teaching and learning method in order to prepare students to be able practitioners. In the wider educational field peer tutoring has been used to foster a deeper understanding of a subject area. Experiments using this method have been carried out extensively in America and are becoming more widespread in this country; however very little material is available on the use of this method in nurse education. The following article explains the use of peer tutoring as a method for developing teaching skills amongst student nurses. Two groups of learners were used in this exercise, the senior learners acting as peer tutors. Evaluation by nurse teachers and both groups of learners was favourable and the peer tutors were able to identify the benefits they received from the exercise. PMID- 2304436 TI - Tradition v Project 2000--something old, something new. AB - Simple introduction of Project 2000 will not, of itself, lead to improved standards of nursing or to better retention of staff. The author believes that senior nursing staff may well revert to traditional ego-defensive stances when faced with new problem-solving learners. Implementation of Project 2000 may lead to worsening relationships, entrenchment of already hardened attitudes, increased role conflict for junior nurses, with a resultant loss of job satisfaction and increased wastage. Some conflict areas which exist in nursing are discussed. It is argued that the attitudes a learner holds towards significant others can be correlated with degrees of role conflict and that role conflict can affect job satisfaction, while loss of job satisfaction can result in wastage. Recommendations regarding action which should be taken prior to implementation of Project 2000 are outlined and conclusions drawn regarding possible outcomes. PMID- 2304437 TI - The standing advisory group for community psychiatric nursing: grasping the nettle? AB - This paper reports on the work of the Standing Advisory Group for Community Psychiatric Nursing Education (SAGCPNE). A precis of the historical development CPN education is provided and a stronger relationship with the Mental Nurses Committee is proposed. It is argued that the educational preparation of community psychiatric nurses is the sine qua non of desirable, high quality, community mental health services and that methods for the identification and protection of adequate financial resources for such preparation must be found. PMID- 2304438 TI - Mentorship--is it a case of the emperors new clothes or a rose by any other name? AB - The author examines and discusses the concept of mentorship. Consideration is given to the development of mentorship in the United States of America, and to the relevance for adoption in this country. Concern is registered at the absence of a clear definition of the term; its inclusion in course approval criteria and the impact of this is considered. In view of changes in Nurse Education the author questions whether preceptorship might be a more appropriate concept to develop. PMID- 2304439 TI - Developing the credibility of continuing education. AB - The paper begins by acknowledging both the need for nursing to be a research based profession, and the reasons for the well-documented theory-practice gap. It goes on to suggest that what is not so well-documented is an examination of the reasons for the commitment gap between basic and continuing education. The relevance of continuing education to clinical staff will be discussed in relation to the change in the content of nursing theory--from the unwieldy 'certainty based' medical model, to a more flexible, thus perhaps 'uncertainty-based' medical model. The paper will explore the author's belief that clinical staff need to feel a sense of security in their knowledge base, which therefore leads them at times to reject nursing theory. The paper proposes that a legal framework for nurses practice gives the clinical staff the security in their practice to view the relevance of new nursing theory. PMID- 2304440 TI - Staff development equated with organisational efficiency. AB - Post basic and continuing education and training courses have always been linked to the requirements of the organisation in which they are based. This article sets out to draw attention to the consequences of productivity expectations on these systems from NHS local management. It highlights the need for an increase in the provision of information from educators to managers to avoid a reductionist view which sees training as the cheapest and therefore the most effective staff development method. PMID- 2304441 TI - Nursing trade union in government hospitals of Hong Kong. PMID- 2304442 TI - Rural obstetric care: where has it gone? AB - Obstetric care in rural Missouri is perched precariously on the edge of non existence. We must act now to reverse the loss of rural general and family practitioners practicing obstetrics to ensure the well-being of mothers and infants in our state. PMID- 2304443 TI - Self-recognition. PMID- 2304444 TI - A strategic plan for the elimination of tuberculosis in the United States. Executive Summary Report. PMID- 2304445 TI - Cancer control and public health in Missouri: a time for action. AB - National reports on cancer mortality now show that most cancer deaths are preventable. The recent national focus on prevention of such chronic diseases may indicate that public health departments need to consider a shift in emphasis from infectious to chronic disease control. PMID- 2304446 TI - Lyme carditis. Severe conduction disorder. AB - Lyme disease in most cases occurs in the states of Connecticut, Wisconsin, Oregon, California, Missouri and parts of the northeastern coast. Showing the exception to the rule, the authors discuss a case in which a patient acquired the disease on the Eastern Shore of Virginia. PMID- 2304447 TI - All-terrain vehicle injuries in central Missouri. AB - Leisure time all-terrain vehicle (ATV) use and injuries are increasing. The authors characterize the riding habits and injury patterns of patients hospitalized for ATV-related trauma and offer suggestions for decreasing ATV injuries. PMID- 2304448 TI - Obstetric care in rural Missouri: the loss of rural general and family practitioners. AB - Family and general practitioners have historically provided a substantial portion of obstetric care in rural parts of the United States, including Missouri. The authors surveyed 328 rural general physicians to determine their participation in obstetrics. Their findings show a dramatic loss of physician obstetric services in rural Missouri and suggest that the dilemma is not likely to be easily remedied. PMID- 2304449 TI - Lobbying guide. PMID- 2304450 TI - Demonstration of both A1 and A2 adenosine receptors in DDT1 MF-2 smooth muscle cells. AB - Adenosine receptors of the A1 and A2 subtypes were characterized in membranes from DDT1 MF-2 smooth muscle cells. These cells possess a high density of A1 adenosine receptors (Bmax = 0.8-0.9 pmol/mg of protein), as measured by both agonist and antagonist radioligands. Agonists compete for [125I]N6-[2-(4-amino-3 iodophenyl)ethyl]-adenosine (A1 receptor-selective radioligand) binding with the following potency series: (R)-phenylisopropyladenosine [(R)-PIA] greater than 5' N-ethylcarboxamide adenosine (NECA) greater than (S)-PIA, indicative of their interaction with A1 adenosine receptors. Agonist competition for [3H]8-(4-[[[(2 aminoethyl)amino]carbonyl)methyl)oxy]phenyl)-1, 3-dipropylxanthine [( 3H]XAC) (an antagonist radioligand for the A1 adenosine receptor) was described by a two state model of 1.3 nM (high affinity state, KK) and 370 nM (low affinity state, KL), with 70% of the receptors in the high affinity state (RH). Addition of guanosine 5'-[beta, alpha-imido]triphosphate (100 microM) shifted the (R)-PIA competition curves to the right to lower affinities. Photoaffinity labeling with the agonist photoprobe [125I]N6-[2-(4-amino-3-iodophenyl) ethyl]adenosine indicates that the A1 adenosine receptor binding subunit is a Mr 38,000 protein. Adenosine receptor agonists [(R)-PIA, NECA, and (S)-PIA] inhibited isoproterenol stimulated adenylate cyclase activity in DDT1 MF-2 cell membranes with IC50 values of 62, 538, and 750 nM, respectively. Inhibition of adenylate cyclase by (R)-PIA was attenuated by the A1 receptor antagonist XAC and following inactivation of Gi with pertussis toxin (100 ng/ml). Using a recently developed A2 adenosine receptor agonist radioligand 2-[4-(2-[( 4 aminophenyl]methylcarbonyl)ethyl) phenyl]ethylamino-5'-N-ethylcarboxamido adenosine (125I-PAPA-APEC), we have demonstrated the presence of A2 adenosine receptors in this cell line. Saturation curves with 125I-PAPA-APEC indicated the Bmax and Kd values to be 0.21 pmol/mg of protein and 4.0 nM, respectively. In competition experiments, NECA was more potent at inhibiting 125I-PAPA-APEC binding than (R)-PIA, with their respective IC50 values being 5.6 and 351 nM. The photolabeled A2 adenosine receptor migrated on sodium dodecyl sulfate polyacrylamide gel electrophoresis with an Mr of 42,000. Finally, adenosine receptor agonists stimulated adenylate cyclase activity by approximately 2-3 fold with the following potency series: PAPA-APEC greater than or equal to NECA greater than (R)-PIA, indicative of their interaction at A2 receptors. These data represent the first demonstration of the presence of both A1 and A2 receptors in a single cell line, DDT1 MF-2 smooth muscle cells. PMID- 2304451 TI - Glucocorticoid regulation of polycyclic aromatic hydrocarbon induction of cytochrome P450IA1, glutathione S-transferases, and NAD(P)H:quinone oxidoreductase in cultured fetal rat hepatocytes. AB - The regulation of polycyclic aromatic hydrocarbon-inducible enzymes, cytochrome P450IA1, NAD(P)H:quinone oxidoreductase, and glutathione S-transferases, by glucocorticoids was investigated using primary fetal rat hepatocyte culture. Treatment of cells in culture with 1,2-benzanthracene (100 microM, 72 hr) resulted in 60-, 2-, and 6-fold increases in cytochrome P450IA1, glutathione S transferase, and NAD(P)H:quinone reductase activities, respectively. The inductive effect of 1,2-benzanthracene on cytochrome P450IA1 and glutathione S transferase (1-chloro-2,4-dinitrobenzene conjugation) activities was potentiated approximately 3- and 2- to 3-fold, respectively, when dexamethasone (0.01-1 microM) was included in the culture medium. In contrast, 1 microM dexamethasone was found not to potentiate the induction of NAD(P)H:quinone oxidoreductase activity by 1,2-benzanthracene. Treatment of cultured hepatocytes with dexamethasone alone, at concentrations of up to 100 microM, resulted in a 2- to 4 fold increase in glutathione S-transferase and NAD(P)H:quinone oxidoreductase activity. Both the induction of glutathione S-transferase activity by high concentrations of dexamethasone alone and the potentiation of 1,2-benzanthracene induction by lower concentrations of dexamethasone were observed for other steroids of the glucocorticoid class in conjunction with a variety of polycyclic aromatic hydrocarbons. Western immunoblot analyses indicated that low concentrations of dexamethasone (0.1-1 microM) potentiated 1,2-benzanthracene dependent induction of cytochrome P450IA1, glutathione S-transferase Ya/Yc subunit and NAD(P)H:quinone oxidoreductase content. Additionally, increased glutathione S-transferase activity in response to concentrations of dexamethasone exceeding 1 microM was associated with concomitant increases in Ya/Yc and Yb subunit content. Potentiation of polycyclic aromatic hydrocarbon induction of cytochrome P450IA1, glutathione S-transferase, and NAD(P)H:quinone oxidoreductase protein content by low concentrations of glucocorticoids and induction of glutathione S-transferase and NAD(P)H:quinone oxidoreductase by high concentrations of glucocorticoids alone indicates the importance of these endogenous compounds in the regulation of some hepatic enzymes involved in xenobiotic metabolism. PMID- 2304452 TI - Binding of warfarin, salicylate, and diazepam to genetic variants of human serum albumin with known mutations. AB - Possible effects of single point mutations on the ligand-binding capabilities of human serum albumin (Alb) were investigated by studying the interactions between the strongly bound drugs warfarin, salicylate, and diazepam and five structurally characterized genetic variants of the protein. Equilibrium dialysis data, obtained with the variants and normal serum Alb, revealed pronounced reductions in high affinity binding of all three ligands to Alb Canterbury (313 Lys----Asn) and to Alb Parklands (365 Asp----His). By contrast, unchanged binding of the drugs was found in the case of Alb Verona (570 Glu----Lys). Different effects on binding were observed for the other two variants. Salicylate was the only drug bound with a lower affinity to Alb Niigata (269 Asp----Gly), whereas binding of both salicylate and diazepam to Alb Roma (321 Glu----Lys) were moderately reduced. In about half of the cases of diminished binding, the primary association constant was reduced by 1 order of magnitude, giving rise to an increase in the unbound fraction of the drugs of 500% or more at therapeutically relevant molar ratios of drug and protein. Changes in protein charge seem to be of only minor importance for reduced binding. More likely, conformational changes in the 313-365 region of the proteins are the main cause for diminished binding of these diverse ligands, which probably have different high affinity binding sites. The specific reduction in salicylate binding after modification of residue 269 may be due to conformational changes at or close to the salicylate binding site. PMID- 2304453 TI - Inactivation of the genotoxic aldehyde acrolein by human glutathione transferases of classes alpha, mu, and pi. AB - Acrolein, a genotoxic aldehyde released in the metabolic activation of the cytostatic drug cyclophosphamide, is inactivated by glutathione transferases either by conjugation with reduced glutathione or by covalent binding to the enzymes in the absence of glutathione. The catalytic efficiency (kcat/Km) with acrolein as a substrate was determined for representatives of the three classes Alpha, Mu, and Pi of human glutathione transferases. Transferase pi exhibited the highest and transferase epsilon the lowest catalytic efficiencies, respectively. As measured by the kcat/Km value, acrolein ranks among the most active substrates known for transferase pi. The irreversible binding of acrolein to the enzymes was monitored as the inactivation of the enzyme activity. Transferase pi reacted significantly more rapidly with acrolein than did transferases mu and epsilon. PMID- 2304454 TI - Requirements for the activation of protein kinase C: comparison of the molecular geometries of phorbol and diacylglycerol. AB - MM2 calculations have been performed on a number of derivatives of phorbol and diacylglycerol (DAG) to establish the molecular features required for the activation of protein kinase C by a detailed comparison of the molecular geometries in these two classes of compounds. For DAG, a dihedral angle of about 60 degrees appears to be required for the oxygens at C2 and C3 because that angle is fixed at this value in phorbols. There is good agreement between the computed Boltzmann distribution for the O1-C1-C2-O2 dihedral angle and NMR results for the same angle in phospholipids, as obtained by others. A conformer of DAG is identified with dihedral angles corresponding to those of beta-phorbols. This conformer, however, is 3.2 kcal/mol above the global minimum found for DAG. The molecular geometry of this conformer is consistent with that of a number of active and inactive rigid analogues of DAG. The preferred conformation in beta phorbol diesters is found to be stabilized by an antiparallel stacking of the ester carbonyl groups. The lack of activity of alpha-phorbol esters appears to be due to differences in a portion of the molecule containing the five membered/seven-membered rings, which are far from the DAG-like end of the phorbol molecule. It is proposed that some of the biological activities of phorbol diesters may be due to this portion of the beta-phorbol molecule, which might represent a second active region, distinct from that resembling DAG. PMID- 2304455 TI - Enantioselective S-oxygenation of para-methoxyphenyl-1,3-dithiolane by various tissue preparations: effect of estradiol. AB - Liver, kidney, and lung microsomes prepared from nonpretreated female Sprague Dawley rats catalyze the NADPH- and oxygen-dependent S-oxygenation of para methoxyphenyl-1,3-dithiolane. Studies on the biochemical mechanism of dithiolane S-oxygenation in liver, kidney, and lung microsomes suggest that this reaction is catalyzed in a diastereoselective and enantioselective fashion by the flavin containing monooxygenase and, to a lesser extent, the cytochromes P-450. This conclusion is based on results examining the effects of selective cytochrome P 450 inhibitors and positive effectors, microsome heat-inactivation treatment, and alternate substrates for the flavin-containing monooxygenase. Liver and kidney microsomes prepared from ovarectomized female rats tended to have decreased S oxygenase activity, compared with nonpretreated female rats, whereas ovarectomized rats pretreated with estradiol had markedly lower S-oxygenase activity. In contrast, lung microsomal S-oxygenase activity, which is low in pulmonary microsomes from nonpretreated female rats, increases 2-4-fold after ovariectomization and estradiol pretreatment. In female Sprague-Dawley rats, estradiol pretreatment is mainly responsible for the large decrease (or increase) in S-oxygenase activity observed in the tissues examined, although it is unlikely that estradiol alone controls flavin-containing monooxygenase S-oxygenase activity. PMID- 2304456 TI - Enantioselective S-oxygenation of 2-aryl-1,3-dithiolanes by rabbit lung enzyme preparations. AB - Pulmonary microsomes, highly purified pulmonary flavin-containing monooxygenase, and highly purified pulmonary cytochrome P-450IIB-4 from pregnant female rabbits catalyze the NADPH-dependent S-oxygenation of a series of 2-aryl-1,3-dithiolanes. The S-oxide is the only detectable product formed during the short time period of the enzymatic reactions. Studies on the biochemical mechanism for S-oxygenation of 2-aryl-1,3-dithiolanes suggest that this reaction is catalyzed preferentially by the flavin-containing monooxygenase, although cytochromes P-450 also contribute to S-oxygenation. This conclusion is based on the effects of a cytochrome P-450 inhibitor, aminobenzotriazole, as well as on studies of the stereoselectivity of the reaction. Although both purified rabbit pulmonary cytochrome P-450IIB-4 and purified flavin-containing monooxygenase have identical diastereoselectivity, producing the (trans)-S-oxide, these monooxygenases possess opposite S-oxygenation enantioselectivity. Pulmonary cytochrome P-450IIB-4 S oxygenates 2-aryl-1,3-dithiolanes almost exclusively at the pro-S-sulfur atom, whereas pulmonary flavin-containing monooxygenase S-oxygenates 2-aryl-1,3 dithiolanes exclusively at the pro-R-sulfur atom. 2-Aryl-1,3-dithiolane S-oxides are S-oxygenated a second time on the S'-sulfide sulfur atom but only by rabbit lung microsomes and pulmonary flavin-containing monooxygenase and not by cytochrome P-450IIB-4. That pulmonary flavin-containing monooxygenase only catalyzes formation of (trans)- and not (cis)-2-aryl-1,3-dithiolane S-oxide formation suggests that the active site of pulmonary flavin-containing monooxygenase exerts great steric limitations on 2-aryl-1,3-dithiolane S oxygenation. PMID- 2304457 TI - Analysis of multiple forms of nuclear factor I in human and murine cell lines. AB - Nuclear factor I (NFI) is a group of related site-specific DNA-binding proteins that function in adenovirus DNA replication and cellular RNA metabolism. We have measured both the levels and forms of NFI that interact with a well-characterized 26-base-pair NFI-binding site. Five different NFI-DNA complexes were seen in HeLa nuclear extracts by using a gel mobility shift (GMS) assay. In addition, at least six forms of NFI were shown to cross-link directly to DNA by using a UV cross linking assay. The distinct GMS complexes detected were composed of different subspecies of NFI polypeptides as assayed by UV cross-linking. Different murine cell lines possessed varying levels and forms of NFI binding activity, as judged by nitrocellulose filter binding and GMS assays. The growth state of NIH 3T3 cells affected both the types of NFI-DNA complexes seen in a GMS assay and the forms of the protein detected by UV cross-linking. PMID- 2304458 TI - Stable transfection of the human parasite Leishmania major delineates a 30 kilobase region sufficient for extrachromosomal replication and expression. AB - To delineate segments of the genome of the human protozoan parasite Leishmania major necessary for replication and expression, we developed a vector (pR-NEO) which can be reproducibly introduced into L. major. This DNA was derived from a 30-kilobase extrachromosomal amplified DNA bearing the dihydrofolate reductase thymidylate synthase gene, with the coding region for neomycin phosphotransferase substituted for that of dihydrofolate reductase-thymidylate synthase and a bacterial origin of replication and selectable marker added. G418-resistant lines were obtained at high efficiency by electroporation of pR-NEO (approaching 10(-4) per cell), while constructs bearing an inverted neo gene or lacking Leishmania sequences did not confer resistance. pR-NEO replicated in L. major and gave rise to correctly processed transcripts bearing the trans-spliced miniexon. Molecular karyotype analysis showed that in some lines pR-NEO DNA exists exclusively as an extrachromosomal circle, a finding supported by the rescue of intact pR-NEO after transformation of Escherichia coli. These data genetically localize all elements required in cis for DNA replication, transcription, and trans splicing to the Leishmania DNA contained within pR-NEO DNA and signal the advent of stable transfection methodology for addressing molecular phenomena in trypanosomatid parasites. PMID- 2304459 TI - Characterization of human myosin light chains 1sa and 3nm: implications for isoform evolution and function. AB - We have isolated a cDNA clone for the human slow-twitch muscle isoform myosin light-chain 1slow-a (MLC1sa) from a skeletal muscle library and for the human nonmuscle isoform myosin light-chain 3nonmuscle (MLC3nm) from a fibroblast library. The nucleotide sequence of both isoforms was determined, and isoform specific probes were constructed. In addition, MLC1sa was subsequently isolated from the fibroblast library. MLC1sa and MLC3nm were found to be very closely related to each other and distant from all other myosin light-chain isoforms so far described. We concluded that MLC1sa arose by duplication of MLC3nm rather than from any other isoform. A comparison was made between all human myosin light chains described to date and a model proposed for the evolution of this multigene family. A comparison between human and chicken myosin light-chain isoforms showed that human isoforms are more similar to their chicken counterparts than to human MLC1sa. The expression of MLC1sa and MLC3nm was studied in humans, rabbits, mice, and rats. MLC1sa was detected at the onset of both human and murine myogenesis in vitro. With development, MLC1sa may be replaced by the other slow-twitch muscle isoform, 1sb, in slow-twitch skeletal muscle, but the proportion of MLC1sa to 1sb expression varies between different species. MLC1sa was detected in nonmuscle cells in humans, mice, and rats. MLC3nm was the major nonmuscle alkaline myosin light chain in all species tested, but its pattern of expression in nonmuscle tissues was not identical to that of beta- or gamma-actin. We have shown that in the human, as in the chicken, one exon is spliced out of the MLC3nm transcript in smooth muscle to give an alternative product. We concluded that all alkali myosin light-chain isoforms may be functionally different. PMID- 2304460 TI - Roles of fetal G gamma-globin promoter elements and the adult beta-globin 3' enhancer in the stage-specific expression of globin genes. AB - The human fetal G gamma-globin and adult beta-globin genes are expressed in a tissue- and developmental stage-specific pattern in transgenic mice: the G gamma gene in embryonic cells and the beta gene in fetal and adult erythroid cells. Several of the cis-acting DNA sequences thought to be responsible for these patterns of expression are located 5' to the G gamma-globin gene and 3' to the beta-globin gene. To further define the locations and functional roles of these elements, we examined the effects of 5' truncations on the expression of the G gamma-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene. We found that sequences between -201 and -136 are essential for expression of the G gamma-globin gene, whereas those upstream of -201 have little effect on the level or tissue or stage specificity of G gamma-globin expression. The G gamma-globin upstream sequences from -201 to -136 were, furthermore, capable of activating a linked beta-globin gene in embryonic blood cells; however, a G gamma-globin fragment from -383 to -206 was similarly active in this assay, and the complete fragment from -383 to -136 was considerably more active than either of the smaller fragments, suggesting the presence of multiple cis acting elements for embryonic blood cells. Our data also suggested the possibility of a negative regulatory element between -201 and -136. These results are discussed in relation to several DNA elements in the G gamma-globin upstream region, which have been shown to bind nuclear factors in erythroid cells. Finally, we observed that removal of the beta-globin 3'-flanking sequences, including the 3' enhancer, from the G gamma-globin upstream-beta-globin hybrid gene resulted in a 25-fold reduction in expression in embryonic blood cells. This suggests that the beta-globin 3' enhancer is potentially active at the embryonic stage and thus cannot be solely responsible for the fetal or adult specificity of the beta-globin gene. PMID- 2304461 TI - Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. AB - The mechanism of ribosome binding to eucaryotic mRNAs is not well understood, but it requires the participation of eucaryotic initiation factors eIF-4A, eIF-4B, and eIF-4F and the hydrolysis of ATP. Evidence has accumulated in support of a model in which these initiation factors function to unwind the 5'-proximal secondary structure in mRNA to facilitate ribosome binding. To obtain direct evidence for initiation factor-mediated RNA unwinding, we developed a simple assay to determine RNA helicase activity, and we show that eIF-4A or eIF-4F, in combination with eIF-4B, exhibits helicase activity. A striking and unprecedented feature of this activity is that it functions in a bidirectional manner. Thus, unwinding can occur either in the 5'-to-3' or 3'-to-5' direction. Unwinding in the 5'-to-3' direction by eIF-4F (the cap-binding protein complex), in conjunction with eIF-4B, was stimulated by the presence of the RNA 5' cap structure, whereas unwinding in the 3'-to-5' direction was completely cap independent. These results are discussed with respect to cap-dependent versus cap independent mechanisms of ribosome binding to eucaryotic mRNAs. PMID- 2304462 TI - Promoter and 11-kilobase upstream enhancer elements responsible for hepatoma cell specific expression of the rat ornithine transcarbamylase gene. AB - The gene for ornithine transcarbamylase (OTC; EC 2.1.3.3), a urea cycle enzyme, is expressed almost exclusively in the liver and small intestine. To identify DNA elements regulating transcription of the OTC gene in the liver, transient expression analysis was carried out by using hepatoma (HepG2) and nonhepatic (CHO) cell lines. The 1.3-kilobase 5'-flanking region of the rat OTC gene directed expression of the fused chloramphenicol acetyltransferase gene in HepG2 cells much more efficiently than in CHO cells. Analysis of deletion mutants of the 5'-flanking region in HepG2 cells revealed that there are at least one negative and two positive regulatory elements within the about 220-base-pair immediate 5'-flanking region. DNase I footprint analysis showed the presence of factors binding to these regulatory elements in nuclear extracts of rat liver and brain, and footprint profiles at the two positive elements exhibited liver specific features. Transient expression analysis also revealed the existence of an enhancer region located 11 kilobases upstream of the transcription start site. The OTC enhancer was able to activate both its own and heterologous promoters in HepG2 but not in CHO cells. The enhancer was delimited to an about 230-base-pair region, and footprint analysis of this region revealed four protected areas. Footprint profiles at two of the four areas exhibited liver-specific features, and gel shift competition analysis showed that a factor(s) binding to the two liver-specific sites is related to C/EBP. These results suggest that both liver specific promoter and enhancer elements regulate expression of the OTC gene through interaction with liver-specific factors binding to these elements. PMID- 2304463 TI - Expression of a foreign gene in a line of transgenic mice is modulated by a chromosomal position effect. AB - Unusual aberrant expression of a foreign gene in a particular transgenic mouse line is often attributed to chromosomal position effect, although proof of this is lacking. An alternative explanation is that expression has been modified by the arrangement of multiple copies of the foreign gene at the insertion site or by mutation or gene rearrangement. We have distinguished between these explanations in the case of one particular transgenic line by recovering the aberrantly expressed foreign DNA and reintroducing it into the mouse genome to produce secondary transgenic mice. The expression pattern of the gene in the secondary transgenic mice was normal, showing that this case of aberrant expression is due to a chromosomal position effect. PMID- 2304464 TI - Correlation between patterns of DNase I-hypersensitive sites and upstream promoter activity of the human epsilon-globin gene at different stages of erythroid development. AB - DNA 5' to the human epsilon-globin gene exhibits unique patterns of DNase I hypersensitive sites (DHS) in three human erythroleukemic cell lines which represent the embryonic (K562), fetal (HEL), and adult (KMOE) stages of erythroid development. We have mapped 10 epsilon-globin DHS in K562 cells, in which the epsilon-globin gene is maximally active. Major sites are located -11.7, -10.5, 6.5, -2.2 kilobase pairs (kbp) and -200 base pairs (bp) upstream of the gene and directly over the major cap site. Minor sites are located -5.5, -4.5, and -1.48 kbp and -900 bp upstream of the cap site. In HEL cells, in which the epsilon globin gene is expressed at extremely low levels, the -11.7-, -10.5-, -5.5-, -4.5 , and -2.2-kbp DHS are no longer detectable; the -200-bp site is approximately 300-fold less sensitive to DNase I; and the -1.48-kbp, -900-bp, and major cap site DHS are 3- to 4-fold less sensitive. Only the DHS located -6.5 kbp relative to the major cap site is detectable at all three stages of erythroid development, including KMOE cells in which epsilon-globin synthesis is undetectable. We suggest that this site may be implicated in maintaining the entire beta-globin cluster in an active chromatin conformation. The five DHS downstream of the -6.5 kbp element possess associated promoters. Thus two distinct types of DHS exist- promoter positive and promoter negative. In HEL cells, all the upstream promoters are inactivated, although the -1.48-kbp and -900- and -200-bp DHS are still present. This suggests that the maintenance of DHS and regulation of their associated promoters occur by independent mechanisms. The inactivation of the upstream promoters in HEL cells while the major cap site remains active represents a unique pattern of expression and suggests that HEL cells possess regulatory factors which specifically down regulate the epsilon-globin upstream promoters. PMID- 2304465 TI - Negative regulation of the human epsilon-globin gene by transcriptional interference: role of an Alu repetitive element. AB - The human epsilon-globin gene has a number of alternative transcription initiation sites which correspond with regions of DNase I hypersensitivity upstream of the canonical cap site. Transcripts originating from the promoters located -4.3/-4.5 and -1.48 kilobase pairs (kbp) and -900 and -200 base pairs (bp) upstream of the major epsilon-globin cap site can, at certain stages of erythroid differentiation, extend through the gene and are polyadenylated. The 350-bp PolIII transcripts, originating within the Alu repetitive element -2.2 kbp upstream of the cap site, extend in the opposite direction from the gene, are nonpolyadenylated, nucleus confined, and are detectable only in mature K562 cells or mature embryonic red blood cells where the epsilon-globin major cap site is maximally transcribed. Fragments containing the promoters located between -4.5 and -4.3 kbp upstream of the gene down regulate transcription from the epsilon globin gene 20- to 30-fold in a transient expression assay in which both erythroid and nonerythroid cell lines were used. This occurs only when the direction of transcription from the -4.3/-4.5-kbp promoters is towards the gene, and we hypothesize that down regulation is caused by transcriptional interference. Fragments containing the Alu repetitive element -2.2 kbp upstream of the gene can overcome down regulation of the epsilon-globin gene by the -4.5 kbp element when interposed in the direct orientation between this element and the epsilon-globin gene. PMID- 2304466 TI - A multicomponent complex is required for the AAUAAA-dependent cross-linking of a 64-kilodalton protein to polyadenylation substrates. AB - A 64-kilodalton (kDa) polypeptide that is cross-linked by UV light specifically to polyadenylation substrate RNAs containing a functional AAUAAA element has been identified previously. Fractionated HeLa nuclear components that can be combined to regenerate efficient and accurate polyadenylation in vitro have now been screened for the presence of the 64-kDa protein. None of the individual components contained an activity which could generate the 64-kDa species upon UV cross-linking in the presence of substrate RNA. It was necessary to mix two components, cleavage stimulation factor and specificity factor, to reconstitute 64-kDa protein-RNA cross-linking. The addition of cleavage factors to this mixture very efficiently reconstituted the AAUAAA-specific 64-kDa protein-RNA interaction. The 64-kDa protein, therefore, is present in highly purified, reconstituted polyadenylation reactions. However, it is necessary to form a multicomponent complex to efficiently cross-link the protein to a substrate RNA. PMID- 2304467 TI - Tumor necrosis factor induces the rapid phosphorylation of the mammalian heat shock protein hsp28. AB - Tumor necrosis factor alpha was found to rapidly phosphorylate the unique mammalian small heat shock protein hsp28 without impairing its cytoplasmic localization and without inducing the synthesis of the heat shock proteins. In contrast to the C-kinase-dependent phosphorylation of hsp28 in response to the tumor promoter phorbol-12-myristate-13-acetate, the heat- and tumor necrosis factor-mediated phosphorylation of this heat shock protein appears to occur independently of C kinase. These observations suggest that a C-kinase-independent phosphorylation of hsp28 may be an early event in the cellular action of tumor necrosis factor alpha. PMID- 2304468 TI - Human erythropoietin gene expression in transgenic mice: multiple transcription initiation sites and cis-acting regulatory elements. AB - Erythropoietin (EPO) is the primary humoral regulator of mammalian erythropoiesis. The single-copy EPO gene is normally expressed in liver and kidney, and increased transcription is induced by anemia or cobalt chloride administration. To identify cis-acting DNA sequences responsible for regulated expression, transgenic mice were generated by microinjection of a 4-kilobase-pair (kb) (tgEPO4) or 10-kb (tgEPO10) cloned DNA fragment containing the human EPO gene, 0.7 kb of 3'-flanking sequence, and either 0.4 or 6 kb of 5'-flanking sequence, respectively. tgEPO4 mice expressed the transgene in liver, where expression was inducible by anemia or cobalt chloride, kidney, where expression was not inducible, and other tissues that do not normally express EPO. Human EPO RNA in tgEPO10 mice was detected only in liver of anemic or cobalt-treated mice. Both tgEPO4 and tgEPO10 mice were polycythemic, demonstrating that the human EPO RNA transcribed in liver is functional. These results suggest that (i) a liver inducibility element maps within 4 kb encompassing the gene, 0.4 kb of 5' flanking sequence, and 0.7 kb of 3'-flanking sequence; (ii) a negative regulatory element is located between 0.4 and 6 kb 5' to the gene; and (iii) sequences required for inducible kidney expression are located greater than 6 kb 5' or 0.7 kb 3' to the gene. RNase protection analysis revealed that human EPO RNA in anemic transgenic mouse liver and hypoxic human hepatoma cells is initiated from several sites, only a subset of which is utilized in nonanemic transgenic liver and human fetal liver. PMID- 2304470 TI - Functional cooperation of lens-specific and nonspecific elements in the delta 1 crystallin enhancer. AB - The expression of the chicken delta 1-crystallin gene is primarily regulated by the action of a lens-specific enhancer 1 kilobase long and located in the third intron of the gene (S. Hayashi, K. Goto, T. S. Okada, and H. Kondoh, Genes Dev. 1:818-828, 1987). The 120-base-long core segment is required for the activity of the delta 1-crystallin enhancer but by itself shows no activity. We analyzed the action of the core and adjoining segments of the delta 1-crystallin enhancer by two different approaches: (i) multiplication of the segments to express any cryptic effect and (ii) competition among enhancers for nuclear factors involved in enhancer action. We found that (i) the core defines a strictly lens-specific element, (ii) an adjoining segment defines an element with a broad specificity with regard to cell type, (iii) these elements cooperate in cis within the delta 1-crystallin enhancer, (iv) the multimers of these elements complete with each other and with delta 1-crystallin and simian virus 40 enhancers in trans apparently without sequence specificity but in a fashion reflecting the strength of the enhancers, and (v) the enhancers in trans do not affect the expression of enhancer-free genes, thereby ruling out the possibility of competition for general transcription factors. The last two observations raise the possibility that the enhancer segments interacting with different sequence-specific factors also interact with one other component involved in enhancer action. PMID- 2304469 TI - Capping of mammalian U6 small nuclear RNA in vitro is directed by a conserved stem-loop and AUAUAC sequence: conversion of a noncapped RNA into a capped RNA. AB - The cap structure of U6 small nuclear RNA (snRNA) is gamma-monomethyl phosphate and is distinct from other known RNA cap structures (R. Singh and R. Reddy, Proc. Natl. Acad. Sci. USA 86:8280-8283, 1989). Here we show that the information for capping the U6 snRNA in vitro is within the initial 25 nucleotides of the U6 RNA. The capping determinant in mammalian U6 snRNA is a bipartite element--a phylogenetically conserved stem-loop structure and an AUAUAC sequence, or a part thereof, following this stem-loop. Wild-type capping efficiency was obtained when the AUAUAC motif immediately followed the stem-loop and when the gamma-phosphate of the initiation nucleotide was in close proximity to the capping determinant. Incorporation of a synthetic stem-loop followed by an AUAUAC sequence is sufficient to covert a noncapped heterologous transcript into a capped transcript. Transcripts with the initial 32 nucleotides of Saccharomyces cerevisiae U6 snRNA are accurately capped in HeLa cell extract, indicating that capping machinery from HeLa cells can cap U6 snRNA from an evolutionarily distant eucaryote. The U6-snRNA-specific capping is unusual in that it is RNA sequence dependent, while the capping of mRNAs and other U snRNAs is tightly coupled to transcription and is independent of the RNA sequence. PMID- 2304471 TI - Two DNA-binding proteins discriminate between the promoters of different members of the major histocompatibility complex class II multigene family. AB - The regulation of major histocompatibility complex (MHC) class II gene expression is a key feature of the control of normal and abnormal immune responses. In humans, class II alpha - and beta-chain genes are organized in a multigene family with three distinct subregions, HLA-DR, -DQ, and -DP. The regulation of these genes is generally coordinated, and their promoters contain highly conserved motifs, in particular the X and Y boxes. We have identified five distinct proteins that bind to specific DNA sequences within the first 145 base pairs of the HLA-DR promoter, a segment known to be functionally essential for class II gene regulation. Among these, RF-X is of special interest, since mutants affected in the regulation of MHC class II gene expression have a specific defect in RF-X binding. Unexpectedly, RF-X displays a characteristic gradient of binding affinities for the X boxes of three alpha-chain genes (DRA greater than DPA much greater than DQA). The same observation was made with recombinant RF-X. We also describe a novel factor, NF-S, which bound to the spacer region between the X and Y boxes of class II promoters. NF-S exhibited a reverse gradient of affinity compared with RF-X (DQA greater than DPA much greater than DRA). As expected, RF X bound well to the mouse IE alpha promoter, while NF-S bound well to IA alpha. The drastic differences in the binding of RF-X and NF-S to different MHC class II promoters contrasts with the coordinate regulation of HLA-DR, -DQ, and -DP genes. PMID- 2304472 TI - A directly repeated sequence in the beta-globin promoter regulates transcription in murine erythroleukemia cells. AB - We have identified a previously undetected cis-acting element in the mouse beta major globin promoter region that is necessary for maximal transcription levels of the gene in the inducible preerythroid murine erythroleukemia (MEL) cell line. This element, termed the beta-globin direct-repeat element (beta DRE), consists of a directly repeated 10-base-pair sequence, 5'-AGGGCAG(G)AGC-3', that lies just upstream from the TATA box of the promoter. The beta DRE motif is highly conserved in all adult mammalian beta-globin promoter sequences known. Mutation of either single repeat alone caused less than a twofold decrease in transcript levels. However, simultaneous mutation of both repeated regions resulted in a ninefold decrease in accumulated transcripts when the gene was transiently transfected into MEL cells. Attachment of the beta DRE to a heterologous promoter had little effect on levels of accumulated transcripts initiated from the promoter in undifferentiated MEL cells but resulted in a threefold increase in transcript levels in induced (differentiated) MEL cells. Similarly, a comparison of the relative effects of mutations in the beta DRE in uninduced and induced MEL cells indicated that the element was more active in induced cells. The increase in beta DRE activity upon MEL cell differentiation and the more pronounced effects of mutations in both repeats of the beta DRE have implications for the mechanism of action of the element in regulating beta-globin transcription and for mutational studies of other repetitive or redundant transcription elements. PMID- 2304475 TI - Gastrointestinal pathology. PMID- 2304473 TI - The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes. AB - All immunoglobulin genes contain a conserved octanucleotide promoter element, ATGCAAAT, which has been shown to be required for their normal B-cell-specific transcription. Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned. Some of these proteins (referred to as OTF-2) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1), is found ubiquitously in all cell types. The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear. We have identified two human pre-B cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro. Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene. Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity. These results suggest that OTF-1, without OTF-2, is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression. PMID- 2304474 TI - Binding of a liver-specific factor to the human albumin gene promoter and enhancer. AB - A segment of 1,022 base pairs (bp) of the 5'-flanking region of the human albumin gene, fused to a reporter gene, directs hepatoma-specific transcription. Three functionally distinct regions have been defined by deletion analysis: (i) a negative element located between bp -673 and -486, (ii) an enhancer essential for efficient albumin transcription located between bp -486 and -221, and (iii) a promoter spanning a region highly conserved throughout evolution. Protein-binding studies have demonstrated that a liver trans-acting factor which interacts with the enhancer region is the well-characterized transcription factor LF-B1, which binds to promoters of several liver-specific genes. A synthetic oligodeoxynucleotide containing the LF-B1-binding site is sufficient to act as a tissue-specific transcriptional enhancer when placed in front of the albumin promoter. The fact that the same binding site functions in both an enhancer and a promoter suggests that these two elements influence the initiation of transcription through similar mechanisms. PMID- 2304476 TI - Improved methods for obtaining colonies of human peripheral blood lymphocytes in vitro for radiation dose-survival studies. AB - Culture conditions were examined for colony formation of human peripheral blood lymphocytes in vitro. It was found that addition of 1% human serum to the medium together with fetal calf serum greatly improved the cloning efficiency and colony size, moreover allogeneic lymphocytes and lymphoblastoid cells are both required as feeder cells for better results. The X-ray dose-survival study showed that the radiosensitivity of lymphocytes remained essentially the same whether the irradiation was performed prior to separation of the lymphocytes from blood or 4 h after addition of phytohemagglutinin to the separated lymphocyte culture; however, the sensitivity was definitely increased as the cell cycle progressed from G0 to G1/S or log phase. PMID- 2304477 TI - Method for alpha-irradiation of blood cultures with short-lived radon-222 decay products. PMID- 2304478 TI - Inhibition of MEL cells' capacity to undergo erythroid differentiation by chemicals added during induction. AB - Erythroid differentiation of murine erythroleukemia (MEL) cells, as induced by dimethyl sulfoxide, can be suppressed by chemicals at very low concentrations, not affecting cell viability and proliferation, if present in the culture medium between 18 and 24 h after addition of the inducer. The effect is apparent on the progeny of the treated cells and is determined, between day 3 and 5 following DMSO induction, as percent value of cells expressing the erythroid phenotype. Cultures showing decreased values are no longer terminal and a large number of clones, incapable of expressing the erythroid phenotype, can be isolated from them. In contrast, induced cultures are terminal if the added chemicals do not decrease the expression of the erythroid phenotype. Incorporation of thymidine into induced cultures reveals that maximal sensitivity of MEL cells to chemicals coincides with DNA duplication. In all affected cells, the inhibition to undergo erythroid differentiation is transmitted from one cell generation to the next. PMID- 2304479 TI - International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC Working Paper No. 10. A new approach to germinal mutation surveillance: pair-wise evaluation of component elements in unidentified multiple congenital abnormalities. AB - In the Hungarian population-based surveillance of germinal mutations, 3 indicator conditions of offspring are being followed, namely 15 sentinel anomalies, Down syndrome and unidentified multiple congenital abnormality. The latter is discussed here as a possible indicator of germinal dominant gene and chromosomal mutations. The component congenital abnormalities of unidentified multiple congenital abnormalities are classified into 45 groups. The component congenital abnormalities were reduced to pairs. A pair is a set of 2 independent component congenital abnormalities in index patients with 2 or more congenital abnormalities. Baseline figures of all component congenital abnormality pairs in 3722 unidentified multiple congenital abnormalities were determined in the study period 1973-1982. The observed data for 1983 were compared with expected occurrences based on baseline figures. This pair-wise evaluation of component elements within unidentified multiple congenital abnormalities seems to be an adequate surveillance method to detect any time cluster of congenital abnormality pairs due to environmental factors including germinal mutagens. PMID- 2304481 TI - Synergistic induction of cytogenetic damage by the homo-aza-steroidal ester of p bis(2-chloroethyl)aminophenylacetic acid in combination with caffeine in human lymphocytes in vitro and in Ehrlich ascites tumour cells in vivo. AB - We studied the effects of caffeine alone or in combination with homo-aza steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid (ASE, NSC 290205) on the frequency of SCEs and lymphocyte proliferation kinetics. Caffeine was found to act synergistically with ASE on the induction of SCEs when the two components were administered in combination. Caffeine was also found to act synergistically with ASE in inducing cell-division delays. Enhanced cytogenetic damage by ASE was observed when Ehrlich ascites tumour cells (EAT cells) were exposed in vivo to caffeine. ASE alone or in combination with caffeine caused a dose-dependent increase in SCE rates and cell-division delays. SCEs were demonstrated in EAT-bearing mice, by the i.p. injection of BrdUrd adsorbed onto activated charcoal, 1 h after the i.p. injection of ASE and/or caffeine. PMID- 2304480 TI - Increased frequency of 6-thioguanine-resistant lymphocytes in peripheral blood of workers employed in cyclophosphamide production. AB - The frequency of 6-thioguanine-resistant peripheral blood lymphocytes has been determined by autoradiography in a control population and a population of cyclophosphamide-exposed individuals. The mean variant frequency in a non-exposed population was found to be 2.76 +/- 1.48 X 10(-5). Subpopulations of smokers and non-smokers revealed statistically significant differences in the variant frequencies, i.e. 3.52 +/- 1.55 X 10(-5) and 2.07 +/- 1.05 X 10(-5) respectively. In 20 out of a total of 23 individuals employed in cyclophosphamide synthesis and manufacturing, the variant frequency of 6-thioguanine-resistant lymphocytes was found to be higher than the maximum individual frequency found in the control population. The mean variant frequency in the cyclophosphamide-exposed population was 13.64 +/- 13.56 X 10(-5), a statistically significant increase as compared to the mean control frequency. There was no correlation between variant frequency and duration of employment suggesting that this test reflects the actual exposure and not a cumulative effect. PMID- 2304482 TI - A sensitive assay for detecting mutations resulting from unequal homologous recombination without phenotypic selection. AB - Naturally occurring mutations are composed of a large number of mutations of many types that include mutations resulting from unequal homologus recombination between repetitive elements. The present paper describes a sensitive method for detecting such mutations without phenotypic selection. This system utilizes a tandemly arranged Vr repetitive sequence comprising 6000 copies in the mouse genome that is present in the spacer of the ribosomal RNA gene. For HincII digests of FM3A cell DNA, the Vr probe provides 4 major bands of 2.7 kb, 1.7 kb, 1.6 kb and 1.35 kb and several minor bands. Newly induced mutations due to unequal homologous recombination are observed as disappearance of the minor bands and appearance of extra bands. With this method a spontaneous mutation was detected in 14 cell clones randomly isolated after 60 days of continuous growth. Exposure to 4 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine for 2 h revealed 4 mutations in 11 clones examined. Culturing the cells after treatment in the presence of 12-O-tetradecanoylphorbol 13-acetate enhanced the frequency, yielding 6 mutations in 5 clones. The assay can skip phenotypic selection prior to analysis of DNA changes and hence provides a direct method for monitoring mutations resulting from homologous recombination in non-biased cell populations. PMID- 2304483 TI - Suppression of 6-TG-resistant mutations in V79 cells and recessive spot formations in mice by vanillin. AB - The antimutagenic effects of vanillin, anisaldehyde, cinnamaldehyde and coumarin were investigated in cultured Chinese hamster V79 cells in vitro. The frequencies of 6-TG-resistant mutations induced by UV or X-rays were decreased by treatment with each compound during the expression time. These decreases were not due to cytotoxic effects on cellular growth or killing effects on damaged cells. The antimutagenic effect of vanillin was also investigated in vivo in the mouse spot test using male PW and female C57BL/10 mice. Female mice were injected intraperitoneally with ethylnitrosourea (ENU) on the 10th day of pregnancy and received 3 successive oral administrations of vanillin. Administration of vanillin decreased the ENU-induced frequency of recessive carrier pups. These results indicate that vanillin acts as an antimutagen in mammalian cells both in vitro and in vivo. PMID- 2304484 TI - Effects of low-dose hydrogen peroxide treatment of V79 cells on killing and mutation by different agents. AB - Benzamide (BA) prevented the induction of repair resulting from a small dose of H2O2 pretreatment of V79 cells. Such pretreatment with H2O2 increased the mutation yield by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or gamma-rays, indicating the error proneness of the induced repair activity. Cycloheximide or BA could suppress the increase in the mutation yield. This induced repair function had no effect on the lesions by ultraviolet light and persisted for about 20 h after which it declined. PMID- 2304485 TI - The effect of microwave radiation on the cell genome. AB - Cultured V79 Chinese hamster cells were exposed to continuous radiation, frequency 7.7 GHz, power density 30 mW/cm2 for 15, 30, and 60 min. The parameters investigated were the incorporation of [3H]thymidine and the frequency of chromosome aberrations. Data obtained by 2 methods (the incorporation of [3H]thymidine into DNA and autoradiography) showed that the inhibition of [3H]thymidine incorporation took place by complete prevention of DNA from entering into the S phase. The normal rate of incorporation of [3H]thymidine was recovered within 1 generation cycle of V79 cells. Mutagenic tests performed concurrently showed that even DNA macromolecules were involved in the process. In comparison with the control samples there was a higher frequency of specific chromosome lesions in cells that had been irradiated. Results discussed in this study suggest that microwave radiation causes changes in the synthesis as well as in the structure of DNA molecules. PMID- 2304486 TI - Localization of breaks induced by vinyl chloride in the human chromosomes of lymphocytes. AB - A group of 67 workers occupationally exposed to VCM was examined for the presence and distribution of breaks along the chromosomal length. Breaks induced by VCM are not randomly distributed as had been expected in a normal population. According to our results there exist highly sensitive and highly resistant locations along the chromosomes to the actions of VCM. The link between the highly sensitive segments of chromosomes, fragile sites and the activation of oncogenes is discussed. PMID- 2304487 TI - Substrate cycling between glucose 6-phosphate and glycogen occurs in Schistosoma mansoni. AB - The regulation of glycogen metabolism in Schistosoma mansoni was studied in vitro with special emphasis on the possible occurrence of substrate ('futile') cycling. The partition of label between carbon atoms 1 and 6 of the glucose units in glycogen was analysed after the incubation of intact worm pairs in the presence of [6-14C]glucose. Under all conditions tested, more than 99% of the label in glycogen was still in the 6 position, demonstrating that glycogen was synthesised not via an indirect pathway involving 3-carbon units, but directly, from glucose. Increasing the glucose concentration stimulated glycogen synthase and decreased the activity of glycogen phosphorylase. An inverse relationship was shown between the actual glycogen content and the rate of glycogenesis. Substrate cycling occurred between glucose 6-phosphate and glycogen. Glucose was incorporated into glycogen during periods of net glycogen breakdown, and vice versa: glycogen degradation occurred during periods of net glycogen synthesis. Under our experimental conditions of net glycogen degradation, the rate of glycogen synthesis as a percentage of that of glycogen breakdown was dependent on the external glucose concentration and ranged from 5 to 68% for 2 to 100 mM glucose, respectively. The synthesis of glycogen during periods of net glycogen breakdown was shown to occur in each individual worm pair. PMID- 2304488 TI - Ca2+ transport in isolated mitochondrial vesicles from Leishmania braziliensis promastigotes. AB - Leishmania braziliensis maintained very low (50 +/- 20 nM) intracellular concentrations of calcium ions under normal conditions, as shown by the fluorimetric indicator QUIN2. Digitonin-permeabilized cells liberated large amounts of calcium ions in the presence of the ionophore A23187, indicating the presence of a large intracellular reservoir for this ion. Given the extraordinary extension of the single giant mitochondrion of Kinetoplastida and the known capacity of mitochondria from other sources to accumulate calcium, we tested the capacity of this organelle to accumulate calcium ions in Leishmania. Coupled mitochondrial vesicles, five-fold enriched in succinate-cytochrome c oxidoreductase, were obtained from promastigotes by gentle grinding (45 s) with glass beads in hypertonic buffer solution, followed by differential centrifugation. These vesicles had a respiratory control ratio of 1.82 +/- 0.15, and two phosphorylation sites (sites II and III) using succinate as electron donor, and were capable of calcium uptake in the presence of several respiratory substrates; this uptake was enhanced in the presence of ADP and Pi and was blocked by classical electron transport inhibitors. Uncouplers such as carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP) and the calcium ionophore A23187 released previously accumulated calcium ions, suggesting that the driving force for the calcium uptake by the vesicles is the respiratory generated electrochemical potential gradient of protons. A study of the affinity of this system for calcium showed that even at 90 microM free calcium, succinate-induced calcium uptake is not saturated while approaching a level of 200 nmol min-1 (mg protein)-1, indicating a low-affinity, large-capacity system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304489 TI - Size-conserved chromosomes and stability of molecular karyotype in cloned stocks of Leishmania major. AB - Molecular karyotypes for 5 stocks of Leishmania major were derived by pulsed field gradient gel electrophoresis and transverse alternating field electrophoresis. Chromosome sizes obtained by the two methods agreed within less than or equal to 50kb. A set of 10 size-concordant chromosome bands between approx. 350-1000 kb was found in all stocks, plus a variable number of polymorphic chromosomes. Cloned gene probes, and DNA purified from individual chromosomes, hybridized to individual size-concordant chromosomes in different stocks, indicating a high degree of sequence homology among bands of similar size. Since the stocks were isolated over a 25-year period in a wide geographic area, we interpret these size-conserved chromosomes to be characteristic of the L. major karyotype. We were unable to identify irreversible genomic rearrangements in Leishmania cloned from the midgut of sandflies or cultivated from the skins of infected mice, which might have explained the origin of the size-variable chromosomes. For stocks that are maintained in the laboratory, the molecular karyotype appears to be a stable characteristic of a cloned population of Leishmania. PMID- 2304490 TI - Voluntary interruption of pregnancy with mifepristone (RU 486) and a prostaglandin analogue. A large-scale French experience. AB - In 2115 women seeking voluntary termination of pregnancy after 49 days of amenorrhea or less, we studied the effect of a single 600-mg dose of mifepristone (RU 486), followed 36 to 48 hours later by the administration of one of two prostaglandin analogues, either gemeprost (1 mg by vaginal suppository) or sulprostone (0.25, 0.375, or 0.5 mg by intramuscular injection). The women were monitored for four hours after prostaglandin administration. Efficacy was indicated by the complete expulsion of the conceptus without the need of an additional procedure. All other results were considered failures, and the pregnancy was then terminated by a surgical method. The overall efficacy rate was 96.0 percent (95 percent confidence interval, 95.0 to 96.8). The failures included persisting pregnancies (1.0 percent), incomplete expulsions (2.1 percent), and the need for hemostatic procedure (0.9 percent). The mean time to expulsion was significantly shorter when sulprostone was given in the high dose (4.5 hours) than when it was given in the two lower doses (13.1 and 19.3 hours) or when gemeprost was given (22.7 hours). The mean duration of uterine bleeding was 8.9 days (range, 1 to 35); one woman received a blood transfusion. Most women had transient abdominal pain after receiving prostaglandin, but there were few other side effects. We conclude that the administration of mifepristone followed by a small dose of a prostaglandin analogue is an effective and safe method for the early termination of pregnancy. PMID- 2304491 TI - Delayed childbearing and the outcome of pregnancy. AB - Whether women who delay childbearing are at increased risk for adverse outcomes of pregnancy is of concern because of the growing proportion of first births to older women. We assessed the effect of advancing maternal age on the outcome of pregnancy in first births in a hospital-based cohort study of 3917 private patients who were 20 years of age or older with a singleton gestation. There was a slight elevation in the risk of having a low-birth-weight infant among women who were 35 years of age or older (adjusted odds ratio, 1.3; 95 percent confidence interval, 0.9 to 1.9) as compared with the risk among women 20 to 29 years of age. However, there was no evidence that women between 30 and 34 or those 35 and older had an increased risk of having a preterm delivery or of having an infant who was small for gestational age, had a low Apgar score, or died in the perinatal period. In contrast, even after controlling for sociodemographic and medical risk factors, we found that women who were 35 or older were significantly more likely to have specific antepartum and intrapartum complications and those who were 30 or older were significantly more likely to have both cesarean sections and infants who were admitted to the newborn intensive care unit. This study suggests that although older primiparous women have higher rates of complications of pregnancy and delivery, their risk of a poor neonatal outcome is not appreciably increased. PMID- 2304492 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1990. A 15-year-old girl with multiple radiolucent bony defects and multiple pulmonary nodules. PMID- 2304493 TI - Mifepristone (RU 486) PMID- 2304494 TI - The "elderly primigravida" in 1990. PMID- 2304495 TI - Cellular origins of hematologic neoplasms. PMID- 2304496 TI - Hypercholesterolemia: whom and how to treat. PMID- 2304498 TI - Fecal impaction. PMID- 2304497 TI - Menopause and coronary risk factors. PMID- 2304499 TI - Ulcerative keratitis among users of contact lenses. PMID- 2304500 TI - Mitochondrial DNA deletions and ophthalmoplegia. PMID- 2304501 TI - Cryptococcal infections in patients with AIDS. PMID- 2304502 TI - Purpura due to ethanol. PMID- 2304503 TI - Primary care in underserved areas and medical education. PMID- 2304504 TI - Reduction of plasma cholesterol levels in normal men on an American Heart Association Step 1 diet or a Step 1 diet with added monounsaturated fat. AB - The design of diets to achieve optimal changes in plasma lipid levels is controversial. In a randomized, double-blind trial involving 36 healthy young men, we evaluated the effects on plasma lipid levels of both an American Heart Association Step 1 diet (in which 30 percent of the total calories were consumed as fat: 10 percent saturated, 10 percent monounsaturated, and 10 percent polyunsaturated fats, with 250 mg of cholesterol per day) and a monounsaturated fat-enriched Step 1 diet (with 38 percent of the calories consumed as fat: 10 percent saturated, 18 percent monounsaturated, and 10 percent polyunsaturated fats, with 250 mg of cholesterol per day). The effects of these diets were then compared with those of an average American diet, in which 38 percent of the total calories were consumed as fat: 18 percent saturated, 10 percent monounsaturated, and 10 percent polyunsaturated fats, with 500 mg of cholesterol per day. The men consumed the average American diet for 10 weeks before random assignment to one of the two Step 1 diets or to continuation of the average diet for an additional 10 weeks. Caloric intake was adjusted to maintain a constant body weight. As compared with the mean (+/- SD) change in the plasma total cholesterol level in the group that followed the average American diet throughout the study (-0.05 +/- 0.36 mmol per liter), there were statistically significant reductions (P less than 0.025) in the plasma total cholesterol level in the group on the Step 1 diet (-0.37 +/- 0.27 mmol per liter) and in the group on the monounsaturated fat enriched Step 1 diet (-0.46 +/- 0.36 mmol per liter). There were parallel reductions in the plasma low-density lipoprotein cholesterol levels in these two groups. Neither the plasma triglyceride levels nor the high-density lipoprotein cholesterol concentrations changed significantly with any diet. We conclude that enrichment of the Step 1 diet with monounsaturated fat does not alter the beneficial effects of the Step 1 diet on plasma lipid concentrations. PMID- 2304505 TI - Immunization of six-month-old infants with different doses of Edmonston-Zagreb and Schwarz measles vaccines. AB - Because measles causes an estimated 2 million deaths per year among children in developing countries, including a substantial proportion of infants less than nine months old--the age at which vaccination is recommended--there has been interest in using different strains of vaccine and higher doses to achieve immunization of younger infants. We conducted a randomized trial of three different doses of Edmonston-Zagreb and of Schwarz measles vaccines in infants to evaluate the effect of the strain and dose of vaccine on the serologic response and acute adverse reactions to vaccination. Six-month-old infants received a standard, medium, or high dose of one of the vaccines, and nine-month-old infants received a standard dose. Antibody levels were measured before and after vaccination, by means of a plaque-reduction neutralization assay, in 1061 six month-olds and 299 nine-month-olds. Edmonston-Zagreb vaccine produced higher rates of seroconversion and seropositivity than comparable doses of Schwarz vaccine. Among the six-month-old infants, the seroconversion rate 18 weeks after vaccination with the standard dose of Edmonston-Zagreb vaccine was 92 percent, that with the medium dose was 96 to 97 percent, and that with the high dose was 98 percent; the rates for the corresponding doses of Schwarz vaccine were 66 percent, 76 percent, and 91 percent, respectively. Higher seroconversion rates were observed with an increase in the dose of either Edmonston-Zagreb (P less than 0.01) or Schwarz (P less than 0.001) vaccine. The seroconversion rates produced by high and medium doses of Edmonston-Zagreb vaccine in six-month-olds were equal to or significantly higher than the rate produced by a standard dose of Schwarz vaccine in nine-month-olds (87 percent). Clinical adverse reactions were not associated with the strain or dose of a vaccine. We conclude that Edmonston-Zagreb vaccine is more immunogenic than Schwarz vaccine in infants and can induce effective immunization against measles at six months of age. PMID- 2304506 TI - Vasovagal syncope after infusion of a vasodilator in a heart-transplant recipient. PMID- 2304507 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 9-1990. A 39-year-old man with hypertension, a renal-artery aneurysm, and eosinophiluria. PMID- 2304508 TI - Potassium supplements for hypertension. PMID- 2304509 TI - Intrapartum fetal monitoring--a disappointing story. PMID- 2304510 TI - Changing the malpractice liability system. PMID- 2304511 TI - Professional liability--a no-fault solution. PMID- 2304512 TI - HIV in intravenous drug users. PMID- 2304513 TI - Atypical mycobacterial infection caused by Mycobacterium marinum. PMID- 2304514 TI - Precautions in the use of ribavirin at the children's hospital. PMID- 2304515 TI - Acute eosinophilic pneumonia. PMID- 2304516 TI - Health care issues in presidential campaigns. PMID- 2304517 TI - Editorial peer review. PMID- 2304519 TI - Animals and friends. PMID- 2304518 TI - Embryos win rights. PMID- 2304520 TI - AIDS in children adds to Romania's troubles. PMID- 2304521 TI - Human genome: keeping them guessing. PMID- 2304522 TI - Animal research legislation: Congress cracks down. PMID- 2304523 TI - Animal rights litigation: activist group under fire. PMID- 2304524 TI - Pasteur inquiry: cancer risk indicated. PMID- 2304525 TI - Agent Orange controversy. PMID- 2304526 TI - More on Shockley. PMID- 2304527 TI - Saying sorry, but not sorry. PMID- 2304529 TI - Ecology: case of the diffusion squirrels. PMID- 2304528 TI - Immunology: questions of presentation. PMID- 2304530 TI - Developmental genetics: a long story and a short tail. PMID- 2304531 TI - The dissolution of semantics. PMID- 2304532 TI - Genetics of long-spurred pheasants. PMID- 2304533 TI - Synthetic tips. PMID- 2304534 TI - Folding pathway enigma. PMID- 2304535 TI - Programmed death of autoreactive thymocytes. AB - T lymphocytes bearing high-affinity T-cell receptors (TCR) for self-antigens are clonally deleted during thymus development. Several recent studies have identified variable domains of the beta-chain of the TCR that are specifically deleted in vivo in mouse strains that express major histocompatibility complex class II molecules in addition to poorly defined self-antigens, including those encoded by the Mls-1a and Mls-2a loci. Deletion of autoreactive cells in these systems occurs in the thymus, and antibody blocking experiments in vivo have implicated the phenotypically immature CD4+CD8+ 'cortical' subset as the target population for clonal deletion. Similarly, studies with transgenic mice bearing autoreactive TCR have provided independent evidence that clonal deletion occurs at the CD4+CD8+ stage of development. But none of these studies directly identified dying autoreactive cells, and the circumstances leading to deletion remain unclear. Here we report that neonatal thymus contains a significant population of phenotypically mature CD4+CD8- cells bearing autoreactive TCR. When placed in short-term culture, a large proportion (60%) of these autoreactive cells die selectively. Furthermore, their death can be prevented by inhibitors of macromolecule (RNA and protein) synthesis, as is the case for glucocorticoid induced death of thymocytes. These data indicate that physiological clonal deletion of autoreactive cells involves 'programmed' cell death, and that it can occur in cells with a mature (CD4+CD8-) surface phenotype. PMID- 2304536 TI - A dimension reduction framework for understanding cortical maps. AB - We argue that cortical maps, such as those for ocular dominance, orientation and retinotopic position in primary visual cortex, can be understood in terms of dimension-reducing mappings from many-dimensional parameter spaces to the surface of the cortex. The goal of these mappings is to preserve as far as possible neighbourhood relations in parameter space so that local computations in parameter space can be performed locally in the cortex. We have found that, in a simple case, certain self-organizing models generate maps that are near-optimally local, in the sense that they come close to minimizing the neuronal wiring required for local operations. When these self-organizing models are applied to the task of simultaneously mapping retinotopic position and orientation, they produce maps with orientation vortices resembling those produced in primary visual cortex. This approach also yields a new prediction, which is that the mapping of position in visual cortex will be distorted in the orientation fracture zones. PMID- 2304538 TI - Software for smart users. PMID- 2304537 TI - Low dimensional chaos in cardiac tissue. AB - Chaos is a term used to characterize aperiodic activity arising in a dynamical system, or in a set of equations describing the system's temporal evolution as a result of a deterministic mechanism that has sensitive dependence on initial conditions. Chaos, in that sense, has been proposed to make an important contribution to normal and abnormal cardiac rhythms. To date, however, descriptions of chaos in heart tissue have been limited primarily to periodically forced cardiac pacemakers. Because many cardiac rhythm disturbances, particularly those initiated or perpetuated by re-entrant excitation, originate from within non-pacemaker cardiac tissues, demonstrations of chaos in non-pacemaker tissue might provide a deterministic explanation for a wide variety of complex dysrhythmias. Here we report experimental evidence for chaotic patterns of activation and action potential characteristics in externally driven, non spontaneously active Purkinje fibres and ventricular muscle. The results indicate that there is an apparent link between the mechanism of low dimensional chaos and the occurrence of reflected responses which could lead to more spatially disorganized phenomena. A detailed mechanism for the low dimensional chaos observed experimentally is pursued using a difference equation model. Critical features of the model include a non-monotonic relationship between recovery time during rhythmic stimulation and the state of membrane properties, and a steeply sloped recovery of membrane properties over certain ranges of recovery times. Besides explaining our results, the analytical model may pertain to irregular dynamics in other excitable systems, particularly the intact dysrhythmic heart. PMID- 2304539 TI - Living with nuclear radiation. PMID- 2304540 TI - Recombinant DNA regulation. India opts for self-control. PMID- 2304541 TI - Biotechnology. Mixed reactions to merger. PMID- 2304542 TI - Conferences. Meetings in north and south. PMID- 2304543 TI - Human Frontiers. Applications under review. PMID- 2304544 TI - Sellafield makes news again. PMID- 2304545 TI - Enzymology. More of the catalytic triad. PMID- 2304546 TI - RNA editing. Sometimes an editor makes sense. PMID- 2304547 TI - Balancing background noise. PMID- 2304548 TI - Inositol phosphate and Ca2+ flow. PMID- 2304549 TI - In vitro replication through nucleosomes without histone displacement. AB - A well-characterized set of proteins encoded by bacteriophage T4 replicates DNA in vitro and generates replication forks that can pass nucleosomes. The histone octamers remain associated with newly replicated DNA even in the presence of excess DNA competitor, and intact nucleosomes re-form on the two daughter DNA helices. It is concluded that nucleosomes are designed to open up transiently to allow the passage of a replication fork without histone displacement. PMID- 2304550 TI - Molecular components of the B-cell antigen receptor complex of the IgM class. AB - The antigen receptors on mature B lymphocytes are membrane-bound immunoglobulins of the IgM and IgD classes whose cross-linking by polyvalent antigens results in B-cell proliferation and differentiation. How these membrane-bound immunoglobulin chains, which lack a cytoplasmic tail, generate a cell activation signal is not at present known. We now show that the IgM molecule is non-covalently associated in the membrane of B cells with two proteins of relative molecular mass 34,000 (Mr 34 K; IgM-alpha) and 39 K (Ig-beta) which form a disulphide-linked heterodimer. Surface expression of IgM seems to require the formation of an appropriate complex between IgM and the heterodimer. A transfection experiment indicates that IgM-alpha is the product of mb-1, a B-cell specific gene encoding a transmembrane protein with sequence homology to proteins of the T-cell antigen receptor-CD3 complex. PMID- 2304551 TI - Ion channels in the nuclear envelope. AB - Cell nuclei are capable of partitioning a wide variety of molecules from the cytosol, including macromolecules such as proteins and RNA, and smaller peptides, amino acids, sugars and Na+ and K+ ions, all of which can be accumulated in or excluded from the nuclear domain. There are two mechanisms behind this compartmentalization: selective retention of freely diffusible molecules, and selective entry through the nuclear envelope. It is generally accepted that the nuclear envelope restricts only the larger molecules. Here we apply the patch clamp technique to isolated murine pronuclei and show that the nuclear envelope contains K(+)-selective channels which have multiple conductance states, the maximal conductance being 200 pS. These channels, which contribute to the nuclear membrane potential, may be important in balancing the charge carried by the movement of macromolecules in and out of the nucleus. PMID- 2304552 TI - A serine protease triad forms the catalytic centre of a triacylglycerol lipase. AB - True lipases attach triacylglycerols and act at an oil-water interface; they constitute a ubiquitous group of enzymes catalysing a wide variety of reactions, many with industrial potential. But so far the three-dimensional structure has not been reported for any lipase. Here we report the X-ray structure of the Mucor miehei triglyceride lipase and describe the atomic model obtained at 3.1 A resolution and refined to 1.9 A resolution. It reveals a Ser..His..Asp trypsin like catalytic triad with an active serine buried under a short helical fragment of a long surface loop. PMID- 2304554 TI - BSE compensation. PMID- 2304553 TI - Motion perception. Switching off an after-effect. PMID- 2304555 TI - Modulation of the motion aftereffect by selective attention. AB - The motion aftereffect is a much studied and well documented phenomenon. After viewing a moving visual pattern for a period of time, the same pattern appears to drift in the opposite direction when it is stopped. Psychophysical experiments involving interocular transfer, dichoptic stimulation, and motion aftereffects contingent upon other visual parameters such as colour, orientation and texture, imply that the motion aftereffect is generated at the level of the visual cortex. It has been hypothesized that cortical neurons specialized for the detection of motion along a particular direction become 'fatigued' during the adaptation period so that the resting equilibrium subsequently shifts in the opposite direction to that of the adapting stimulus, giving rise to the sensation of the aftereffect. I have found that if observers are engaged in a separate discrimination task superimposed on a moving textured background, the subsequent motion aftereffect to the background is considerably reduced. It seems that motion aftereffects are susceptible to attentional mechanisms. PMID- 2304556 TI - Role of self-peptides in positively selecting the T-cell repertoire. AB - The fate of an immature thymocyte is determined by the specificity of its alpha beta T-cell receptor. Only cells expressing receptors that interact with sufficient affinity with major histocompatibility complex (MHC) molecules expressed on thymus epithelial cells are positively selected and go on to mature and seed the peripheral lymphoid organs. The H-2Kb class-I MHC molecule positively selects for the maturation of cytotoxic T lymphocytes that will respond in the periphery to H-2Kb cells presenting a foreign peptide. We have now analysed the ability of variant H-2Kb molecules to positively select T-cells that respond to H-2Kb with ovalbumin. Our results indicate that self-peptides, presented in the groove of the class-I molecule on thymus epithelial cells, are critically involved in positive selection of the T-cell repertoire. Furthermore, the ability of four different H-2Kb variants to select this response in the thymus correlates with their ability to present the ovalbumin peptide, indicating that a self-peptide mimic of the foreign peptide could be involved in positive selection. PMID- 2304557 TI - p-methoxyphenol: chemical basis of stench of a female butterfly. Defense mechanisms of arthropods, No. 91. PMID- 2304558 TI - Getting down to cases. PMID- 2304559 TI - Young people: write here, write now. PMID- 2304560 TI - The North Carolina Medical Journal and its peers. PMID- 2304561 TI - Celebration of the 50th anniversary of the North Carolina Medical Journal. PMID- 2304562 TI - Immunization: injection/protection. PMID- 2304563 TI - Is the medical record dangerous to our health? PMID- 2304564 TI - Child safety is not accident. A 50-year dilemma. PMID- 2304565 TI - Hazards of wheelchairs. PMID- 2304566 TI - In appreciation of Dr. Potts's article. PMID- 2304568 TI - On practicing medicine in today's world. PMID- 2304567 TI - Sport psychology. PMID- 2304569 TI - [Cutting one's own wrist]. PMID- 2304570 TI - [Surgery of the hand in The Netherlands]. PMID- 2304571 TI - [Polydactyly]. PMID- 2304572 TI - [Ray amputation of the hand]. AB - The aim of a ray amputation is to improve the cosmetic appearance and function of the hand after finger amputation. Pain, reasons of appearance and impaired function of amputation stumps are good indications. The patient's occupation, hobbies, handedness and emotional attitude regarding the amputation should be assessed when ray amputation is considered. PMID- 2304573 TI - [Osteoid osteoma and osteoblastoma]. AB - A follow-up study, based on clinical, radiological and pathological information was performed of 20 patients who had suffered from an osteoid osteoma and of three patients who had been treated for an osteoblastoma in the period 1978-1988. 50% of the patients mentioned both pain at night and a good reaction to salicylates. In 87% of the cases a correct diagnosis was made with the aid of conventional radiography, tomography and bone scanning. Primary treatment consisted of intracapsular (mostly piecemeal) excision in all cases. A local recurrence was observed in one patient with osteoid osteoma and in two with osteoblastoma. At the time of this follow-up study none of the 23 patients had complaints. Histopathological examination did not reveal any difference between the two types of bone tumour. PMID- 2304575 TI - [A bilateral hand replantation]. AB - We describe a patient whose both hands were amputated at the level of the wrist in an accident with a farm machine. Both hand were replanted. In spite of an extremely severe injury and consequently a bad prognostic situation an acceptable functional result was obtained. This patient is capable of performing his daily activities reasonably well. He can also ride a bicycle and drive his car. PMID- 2304574 TI - [The treatment of mallet finger: Stack splint or tenodermodesis]. AB - In a retrospective study the results of conservative and operative treatment of mallet fingers (n = 86) were evaluated. The results of Stack splint therapy (n = 59) were disappointing. There was a good result in only 32%. Mallet fingers associated with avulsion fracture (n = 24) give better results (42% 'good') than mallet fingers due to tendon rupture (n = 35) (26% 'good'). With operative treatment (n = 27), consisting of tenodermodesis in combination with internal Kirschner wire fixation, there was a good result in 89%. Surgery was used not only if conservative treatment failed, but also as primary therapy. In case of tendogenous mallet finger the results of surgery are significantly better than those of conservative therapy (p less than 0.00001). Based on our retrospective study we suggest that the tenodermodesis with K-wire fixation be considered not only in cases where conservative treatment fails, but also as primary treatment of tendogenous mallet finger. In mallet finger with avulsion fracture conservative treatment appears to be the treatment of choice. PMID- 2304576 TI - [Laboratory findings for the preoperative assessment of patients with otherwise no organic disorders]. PMID- 2304577 TI - [Autopsies in primary health care, nursing homes and institutes for the mentally retarded]. PMID- 2304578 TI - [Aspiration and sclerosing of the scrotal cyst; a simple ambulatory treatment]. PMID- 2304579 TI - [Psychosocial aspects of heart transplantation; 4-year experience]. AB - The psychosocial aspects of heart transplantation are described on the basis of the experience gained with these patients in the University Hospital Rotterdam (Dijkzigt) from 1984 to 1988. Quality of life before and after heart transplantation was determined using a comprehensive patient questionnaire. This questionnaire was presented by means of a personal computer. Forty-eight patients completed the pretransplant questionnaire. Data on the quality of life 4 and 13 months after transplantation were available for 33 and 20 patients, respectively, mainly due to the limited observation time. Severe anxiety and depressive mood were the predominant features of patients before transplantation. After transplantation the level of anxiety returns to normal within four months. However, sleep disturbances and depressive feelings may persist. Despite physical recovery, only few return to full or partial employment. Our findings confirm international experience and suggest appropriate psychosocial support in the period following the transplantation procedure. PMID- 2304580 TI - [Anaphylaxis following use of polidocanol]. AB - Three female patients had serious anaphylactic reactions to sclerotherapy with polidocanol (Aethoxysklerol) within 15 minutes after administration for varicose veins in the legs. Two of them received the drug for the first time. The first patient developed cardiac arrest which was successfully treated. The second patient showed signs of an adult respiratory distress syndrome, while in the third the ECG was compatible with cardiac ischaemia. Recovery was complete and uneventful in all patients. The incidence of allergic reactions to polidocanol has been estimated at 1:10,000. In view of the considerable underreporting of adverse reactions we feel that the frequency of severe anaphylactic reactions to this drug may be underestimated. PMID- 2304581 TI - [Eurothemes. Hippocrates and the European pendulum of the ethical clock]. PMID- 2304582 TI - [Eurothemes. Luxury problems and the courage to set priorities]. PMID- 2304584 TI - [Obstructive sleep apnea in childhood]. PMID- 2304583 TI - [The effect of admission to the geriatric department of a general hospital on drug utilization of the elderly]. PMID- 2304585 TI - [Prevalence and risk factors of Chlamydia trachomatis infections in clients of a venereal disease outpatient clinic in Amsterdam]. PMID- 2304586 TI - [Vitamins]. PMID- 2304587 TI - [Light diabetes mellitus, severe sequelae]. PMID- 2304588 TI - [The prevalence of late complications of type II diabetes mellitus]. AB - Prevalence of late complications determined in a representative group of 137 patients with type II diabetes mellitus and a control group of 128 persons without diabetes from the same population. Retinopathy was not rare in type II diabetes mellitus (prevalence 35%), but only 50% of diabetic patients had proper ophthalmological care. Microalbuminuria was found in 42% of the patients with diabetes mellitus, although serious renal dysfunction was seldom found. The ratio of serious diabetic foot problems was 5%. Neuropathy and macrovascular problems occurred more frequently in the diabetic group, but above 70 years of age there was a remarkable reduction in difference between diabetics and non-diabetics with regard to these complications. In microalbuminuria the same tendency was observed. The cause of this reduction in difference at an older age is discussed. PMID- 2304589 TI - [A survey of the epidemiology of breast cancer in The Netherlands]. AB - Breast cancer is responsible for the main part of the total cancer incidence (+/- 30%) and cancer mortality (+/- 20%) among Dutch women. Due to aging of the Dutch population alone, the absolute numbers of breast cancer cases and deaths will increase considerably. Risk factors for breast cancer give no clues for primary prevention. By means of periodic screening patients are diagnosed at an earlier stage of disease, with a better prognosis. Even without a screening programme symptomatic women are diagnosed at earlier stages of disease. This paper gives a review of trends in breast cancer incidence and mortality in The Netherlands, as well as a risk profile of breast cancer patients and the relation between disease stage and survival. Its purpose is to obtain a better insight into the intended effects of the national breast cancer screening programme. PMID- 2304590 TI - [Observed effects of the mass screening program for breast cancer in Nijmegen in 1975-1986]. AB - Since January 1975, the start of the screening programme for breast cancer in the city of Nijmegen, The Netherlands, over 14 years have elapsed. Data up to the end of 1986 have been processed and are presented in this article. The younger the birth cohort, the higher the attendance rate. In the course of the screening programme, attendance rates decline. Referral rates are highest in the first screening round and for the eldest birth cohort. Detection rates increased during the most recent screening rounds, after an initial decrease during the earliest rounds. They are higher for the eldest birth cohort also. The relative number of interval carcinomas is highest among younger women (as related to the screening detected carcinomas). PMID- 2304591 TI - [Splenectomy as therapy for esophageal varices in a myeloproliferative syndrome]. AB - We describe the history of a man aged 73 with a myeloproliferative syndrome and massive splenomegaly, who was admitted with bleeding oesophageal varices. After sclerotherapy and other conservative measures had failed to stop the bleeding, splenectomy was performed. Liver biopsy obtained at the time of splenectomy showed extramedullary haematopoiesis and no signs of cirrhosis. Six weeks after the operation no varices were present any more. Studies of the pathogenesis of portal hypertension in splenomegaly of different causes show the importance of the increased splenic blood flow as one of the main contributory causes to this specific type of portal hypertension. Therefore this type of portal hypertension can probably be cured by splenectomy, as we saw in our patient and as has been described in several case reports. PMID- 2304592 TI - [The future of primary health care]. PMID- 2304593 TI - [Predictive characteristics for early mortality in patients on the waiting list for aortocoronary bypass surgery]. PMID- 2304594 TI - [Selection of medical residents for surgery education in The Netherlands]. PMID- 2304595 TI - [Percutaneous transhepatic bile duct drainage, 10 years following its introduction]. PMID- 2304596 TI - [Telephone consultation on Lyme disease]. PMID- 2304597 TI - [Pain in the arm in breast carcinoma ]. PMID- 2304598 TI - [Orthomolecular food preparations]. PMID- 2304599 TI - [Roentgen studies and endoscopy in dyspepsia]. PMID- 2304600 TI - [Assessment of the severity of dementia: patient and caregivers]. PMID- 2304601 TI - [Minor symptoms in family practice; pityriasis versicolor]. PMID- 2304602 TI - [Dietary intervention in occupational medicine]. AB - In two groups of employees (19 offshore workers and 62 office personnel) we attempted to improve dietary habits by information and a change in the canteen supply of meals in the former and by information only in the latter group. Measurements of total plasma cholesterol and diastolic blood pressure were carried out in order to demonstrate the effect and to motivate the participants, who had volunteered. In the office group a statistically significant decrease of both parameters was found (cholesterol: 5.7 (1.3) mmol/l vs. 4.9 (1.0) mmol/l, p less than 0.01; blood pressure: 89.1 (11.1) mmHg vs. 82.3 (10.3) mmHg, p less than 0.01). This showed that such an intervention is feasible within a company. Easily demonstrable parameters, a simple intervention design, active participation of management, good communication, frequent assistance by the members of the project team and participation in a group are important factors for the success of the intervention. PMID- 2304603 TI - [Dietary calcium content and prevention of postmenopausal osteoporosis]. PMID- 2304604 TI - [The obstinacy of a profession]. PMID- 2304605 TI - [From incident to precedent, a far-reaching judgment]. PMID- 2304606 TI - [Dose- and time-dependent dexamethasone effects in cold lesion-induced brain edema in the rat. Experimental research accompanying the German Ultrahigh Dexamethasone Head Injury Study (GUDHIS)]. AB - Experiments in 157 rats were carried out to establish that dose and time of initial dexamethasone therapy after head injury to counteract brain edema are decisive for the antiedematous effect (dose/time response relationship). For this purpose various human doses (weight-related conversion): 20 mg, 100 mg, 500 mg or 2500 mg of dexamethasone with different intervals from the injury: 10 min, 20 min, 40 min or 80 min, were administered in the model of cold lesion induced brain edema. Injury-induced (without therapy), the edema and sodium values increased markedly, and the potassium values decreased. Administration of dexamethasone produced statistically significant dose- and time-dependent effects tending to achieve physiological conditions: An optimal dose of 500 mg of dexamethasone had the highest antiedematous effect, while with still higher doses the effects must be expected to recede again or even be damaging. As expected, pretraumatic dexamethasone doses had the greatest antiedematous effect: reduction by 49%. On administration up to about half an hour after the injury, clearly relevant effects (up to 28%) were still measurable. With longer time intervals between injury and initial dexamethasone administration, e.g. 1 1/2 hours, a measurable but less relevant edema reduction by about 10% can be expected. All posttraumatic effects were achieved experimentally with a maximal dexamethasone therapy period of 21 hours. If similar results are obtained in corresponding clinical studies, the practical recommendation--at least from the animal experimental viewpoint--would be to administer ultra-high cortisone doses (e.g. 500 mg of dexamethasone) as early as possible within the first 2-3 hours after head injury. A cortisone therapy period of more than 2 or 3 days does not appear appropriate. In general no side effects are to be expected with this therapy regimen. PMID- 2304607 TI - [Inflammatory paranasal sinus processes and ophthalmoplegia--the expanded diagnostic potentials via computed tomography and magnetic resonance tomography]. AB - The ethmoidal sinus often plays a key role in recurring infectious sinusitis. Infections arising from this area are the cause of failure of some conventional and radical operative therapies. The case studies presented here demonstrate that transnasal surgery of the ethmoidal sinus because of an inflammatory process, can cause serious complications. Worsening of the vision with opacity of the paranasal sinuses is not always due to an inflammation. Corresponding disease courses which indicate a connection between eye function disturbances and processes of the paranasal sinuses are presented. A correlation between inflammatory and tumorous diseases of the adjacent paranasal sinuses with ophthalmologic signs can be shown in many patients via computed tomography and magnetic resonance imaging. These methods contribute to the diagnosis of the disease, determination of complications, differential diagnostic evaluation of benign and malignant space-occupying lesions, tumour staging, therapy planning, control of the disease course, early recognition of tumour recurrence and documentation. PMID- 2304608 TI - [Treatment of vegetative status with dorsum column stimulation]. AB - We have already reported that DCS (Dorsum Column Stimulation) alleviates the clinical symptoms of patients in vegetative status. Since then, we have accumulated information about 23 cases that have been treated by DCS therapy. In this paper, we describe the clinical outcome and compare cases where the treatment was effective with those where it was non-effective to evaluate the indications for further use of this treatment. RESULTS: 1) Eight of these cases showed good clinical improvement. 2) Most of the cases where the treatment was effective were young. Starting neurostimulation early brought about better clinical effects. 3) The clinical effects appeared 1-12 months after the start of the neurostimulation. 4) CT findings in the cases which had been treated effectively showed no marked cerebral atrophy, and no bilateral large diffuse low density areas not involving the thalamus. Neither did they show any definite and large low-density areas in the brainstem. In conclusion, when the dorsum column was stimulated to treat vegetative status in which CT disclosed none of the abnormal findings described above, it increased r-CBF, enhanced the metabolism of catecholamine, and brought clinical improvement. PMID- 2304609 TI - [Disturbance of inhibitory capacity of endothelial cell for platelet adhesion or aggregation following experimental subarachnoid hemorrhage]. AB - Time sequential changes of the endothelial cells of feline basilar arteries after experimental subarachnoid hemorrhage (SAH) were studied morphologically and functionally under the scanning electron microscope (SEM). Experimental SAH was induced by the two-hemorrhage method, and the basilar artery was removed at 1 hour, or 2, 4, 7, or 14 days respectively after the 1st cisternal blood injection. At each stage, morphological changes of the luminal surface and endothelial cells of the basilar artery were observed by SEM. In another group, adenosin diphosphate (ADP) was infused through the right vertebral artery at the various stages mentioned above, for the purpose of activating platelets, and the basilar artery was then removed. The platelet adhesion or aggregation on the luminal surface was observed quantitatively also by SEM, for evaluating the inhibitory capacity of the endothelial cells upon platelet adhesion or aggregation after SAH. The fold formation of the arterial luminal surface and the ballooning of the endothelial cells were observed initially at 1 hour and 2 days respectively after the 1st cisternal blood injection. The latter findings became most remarkable during the 4 to 7 days after the said blood injection. They were accompanied by intercellular gap formation. None of these findings were seen, however, in the specimens taken 14 days after the said blood injection. In the group with pre-sacrificing ADP infusion, adhesion or aggregation of platelets on the arterial luminal surface was scarcely seen before the second day, but became remarkable 4 to 7 days after the 1st cisternal blood injection, and were reduced by the time 14 days had passed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304610 TI - [Clinical study on developmental hydrocephalus and its operative timing in lumbo sacral meningomyelocele]. AB - Nine infants with lumbo-sacral meningomyelocele were evaluated in the diagnosis and the operative timing of hydrocephalus. Seven cases received early operation for meningomyelocele within 36 hours after birth. Two cases with closed meningomyelocele were operated on 8 days and 32 days after birth. All of them were not infected in the central nervous system before and after its surgery. Five out of nine cases had rapidly developed hydrocephalus within a few weeks, and received ventriculo-peritoneal shunt (Shunt group: Case1-5). Two cases with gradual enlargement of the lateral ventricles and two cases with normal development have been observed without shunt procedure (Non-shunt group: Case 6 9). The authors recorded the head circumference, Evans' index on CT, and intracranial pressure of those infants at birth and following days. The head circumference at birth was almost within a normal size in both groups. On the other hand, an average of Evans' index in shunt group at birth was greater than that of non-shunt group. Moreover, the growth rate of head circumference and lateral ventricle of shunt group were more markedly increased than that of non shunt group. The head circumference and the ventriculomegaly on a computed tomography at birth were poor prediction of hydrocephalus, however, there was positive correlation between the rate of head growth and the rate of hydrocephalic development. That is to say, the growth rate of a head circumference and growth of Evans' index suggested the prediction of a progressing hydrocephalus during the first few weeks. PMID- 2304611 TI - [A case of hemangioblastoma with subarachnoid dissemination]. AB - A case is reported in which a diffuse subarachnoid dissemination occurred after successful removal of a posterior fossa hemangioblastoma. The patient was a 51 year-old man who suffered from headache and gait disturbance, and who was admitted to our hospital on September 25, 1985. Neurological examination revealed trunkal ataxia and increased intracranial pressure. A CT scan with contrast media revealed a high-density lesion with surrounding low-density area in the posterior fossa. Right vertebral angiography demonstrated a round tumor stain behind the medulla oblongata, which was fed by the right posterior inferior cerebellar artery. The complete resection of the tumor was carried out. A biopsy specimen from the tumor showed a picture characteristic of hemangioblastoma. Fourteen months later the patient was readmitted due to the sudden onset of disturbance of consciousness. A CT scan revealed a large intracerebral hematoma in the right putaminal region. Right carotid angiography demonstrated two small tumor stains in the right temporal lobe. An emergency operation to extirpate the hematoma was performed. But the disturbance of consciousness did not improve, and the patient died. At necropsy a lot of small round tumors were recognized at the surface of the bilateral cerebral and cerebellar cortex. They were present in the subarachnoid space and partially invaded the cerebral and cerebellar parenchyma, extending through Virchow-Robin's space. There was no recurrence of the tumor at the site of the original operation. No doubt, a subarachnoid dissemination had occurred. However the histological findings of tumors were similar to the findings recorded in the first biopsy. PMID- 2304612 TI - [Clinical diagnosis of gliomatosis cerebri by radioimages]. AB - Gliomatosis cerebri (GC) is a rare clinical entity characterized by diffuse and infiltrative overgrowth of the tumor cells. Most of the previously reported cases of GC were autopsy cases because the clinical diagnosis of GC has been difficult. The authors report four cases diagnosed clinically as GC. Cases 1 and 2 are females aged 19 and 69. Cases 3 and 4 are males aged 47 and 50. In the first three cases, CT findings were almost normal. MRI study, especially on its T2 weighted image (T2W1), clearly demonstrated the wide extent of the infiltration of the tumor cells along the white matter. The last case occurred in the pre-MRI era, but contrast enhanced CT showed a bilateral periventricular high density area accompanied by diffuse low density white matter. Three of them underwent echo-guided needle biopsy, and one underwent partial excision of the lesion. Histological diagnosis was glioblastoma in Cases 1 and 4, and anaplastic astrocytoma in Cases 2 and 3. Difficulty in the clinical diagnosis of GC has been based on the fact that traditional imaging studies, including CT, can not clearly show the extent of tumor cell infiltration. MRI study is a very sensitive imaging technique which can easily demonstrate the area infiltrated by glioma cells. So we may be able to make clinical diagnosis of GC, coupling the data from MRI study and brain biopsy. The authors expect that accumulation of clinical experiences of GC may give useful information for the investigation of "invasion", which is one of the major problems in the treatment of malignant gliomas. PMID- 2304613 TI - Effects of clonidine and yohimbine, alone and in combination with morphine, on supraspinal analgesia. AB - Morphine raised the threshold for escape from aversive electrical stimulation, delivered to the mesencephalic reticular formation. Clonidine, given alone, had no effect; however, when administered with morphine it blocked the analgesic effect of morphine. Conversely, clonidine, but not morphine, increased the latency to respond to the aversive stimulation, suggesting that clonidine may not have analgesic properties but may merely impair the ability of the animal to respond to the nociceptive stimulation. Yohimbine produced hyperalgesia and also blocked the effect of morphine. These findings are similar to those seen with dopamine agonists and may be related to the effects of yohimbine on the release of dopamine. PMID- 2304614 TI - Opposite changes in turnover of noradrenaline and dopamine in the CNS of ethanol dependent mice. AB - Turnover rates of noradrenaline and of dopamine were examined in regions of the CNS (brainstem, frontal cortex, hippocampus, striatum) and in cardiac tissue of mice that had ingested ethanol for 2 or 7 days and during withdrawal of ethanol. Turnover of neurotransmitters was assessed from the accumulation of dihydroxyphenylalanine and from the depletion in levels of noradrenaline, dopamine and their deaminated metabolites in tissue, after irreversible inhibition of aromatic L-amino acid decarboxylase with DL-alpha monofluoromethyldopa. There were no consistent changes in the turnover of noradrenaline or dopamine after 2 or 7 days of continuous ingestion of ethanol, but at the time that animals exhibited peak ethanol-withdrawal symptoms (8 hr after ethanol consumption was stopped), the turnover of dopamine in the striatum was markedly decreased to less than a third of that observed in control animals, whereas the turnover of noradrenaline in the brainstem was increased by a half. The changes in turnover of neurotransmitters in specific regions of the brain may reflect alterations in neuronal activity that result from withdrawal of ethanol, or may be determinants of particular ethanol-withdrawal symptoms. PMID- 2304615 TI - Alteration of metabolism of acetylcholine induced by 2-deoxy-D-glucose in the gastroduodenum of the rat. AB - 2-Deoxy-D-glucose (2-DG) administered intraperitoneally, dose-dependently increased the secretion of gastric acid, and the changes were comparable with those on the activity of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) in the stomach. Double-reciprocal plot analysis of the increased activity of CAT and AChE, induced by 2-DG, showed that the changes were due to the increase of Vmax, with no change in the Km-value for the substrates. The uptake of [3H]choline and subsequent synthesis of [3H]ACh was observed in the forestomach, corpus and antrum of the stomach and in the duodenum. 2-Deoxy-D glucose significantly increased the uptake of [3H]choline and synthesis of [3H]ACh in every region of the stomach and in the duodenum, in a dose-dependent manner. The increase of secretion of gastric acid, induced by 2-DG paralleled that of uptake of [3H]choline and synthesis of [3H]ACh at an early stage. The conversion of [3H]choline taken up to [3H]ACh was negligibly influenced by 2-DG. Neither the content of ACh and choline, nor the turnover rate of ACh, were changed by administration of 2-DG. 2-Buten-4-olide (2-B4O), which inhibits the activity of the vagus nerve through the central nervous system, prevented 2-DG induced uptake of [3H]choline and subsequent synthesis of [3H]ACh, as well as the increase in secretion of gastric acid. These results suggest that the uptake of [3H]choline and subsequent synthesis of [3H]ACh are closely related to the neuronal activity of the vagus nerve, and that cholinergic neuronal activity is dependent upon quantitative changes of metabolism of ACh in the gastroduodenum. PMID- 2304616 TI - Involvement of the cholinergic system in haloperidol-induced release of dopamine from slices of striatum in the rat. AB - The effects of cholinergic and anticholinergic drugs on spontaneous or haloperidol-induced release of dopamine (DA) were studied in vitro. The slices of striatum were placed in a chamber and continuously superfused with Krebs' solution, containing various concentrations of haloperidol, with or without atropine, d-tubocurarine (d-TC), tetrodotoxin (TTX), physostigmine or carbachol. Haloperidol, enhanced the release of endogenous DA from the slices of striatum at an EC50 value of 25.6 microM. The effect of haloperidol was significantly reduced by atropine (2.5 microM), while it was unaffected by d-TC (10 microM) and TTX (1 microM). In contrast, physostigmine (3.7 microM) significantly increased the haloperidol-induced efflux of DA from the slices of striatum. In addition, acetylcholine (ACh), in the presence of physostigmine or carbachol, enhanced the basal efflux of DA at EC50 values of 2.8 microM and 83 microM, respectively. The effect of ACh on the efflux of DA was antagonized by atropine. These data suggest that haloperidol-induced release of DA is, at least partially, mediated by the activation of muscarinic ACh receptors located in the striatum. PMID- 2304617 TI - A novel action of deltamethrin on membrane resistance in mammalian skeletal muscle and non-myelinated nerve fibres. AB - The pyrethroids, deltamethrin and cismethrin, were assessed for their ability to change membrane conductance directly in skeletal muscle and indirectly in non myelinated nerve fibre preparations from the rat. In diaphragm muscle fibres of the rat, input resistance was significantly increased (35%) by deltamethrin but not by cismethrin, compared with solvent alone. In perfused vagus nerve from the rat, the amplitude of the post-tetanic hyperpolarization was significantly increased (100%) by deltamethrin both in vitro and ex vivo but not by cismethrin or solvent. In both test systems the actions of deltamethrin were abolished by changing the perfusate to a low chloride solution. The enhancement of amplitude of post-tetanic hyperpolarization by deltamethrin was reversed by ivermectin, a compound known to increase the resting chloride flux in neuronal preparations. Depolarizing afterpotentials, indicative of a prolongation in sodium conductance, did not develop until 0.5-1.0 hr after the enhancement of the amplitude of post tetanic hyperpolarization by deltamethrin in the vagus preparations. The amplitude of post-tetanic hyperpolarization was not enhanced by exposure of the vagus to veratrine. These observations reinforce the conclusion that the enhancement of post-tetanic hyperpolarization by deltamethrin is not the result of intracellular accumulation of sodium. In addition, the chloride-dependent nature of the effects of deltamethrin, in both muscle and non-myelinated nerve, suggests that they are in both cases due to a reduction in resting membrane chloride conductance. This novel action of deltamethrin would be expected to amplify the effect of prolonged sodium current and thus influence the actions on excitable membranes both directly and indirectly. PMID- 2304618 TI - Halothane inhibits 5-hydroxytryptamine uptake by synaptosomes from rat brain. AB - The activity of 5-hydroxytryptamine (serotonin; 5-HT) in the central nervous system modulates sleep, the perception of pain and other functions of the body which might possibly relate to mechanisms of general anesthetic action. While administration of anesthetics has inconsistent effects on the content of 5-HT in brain, in vivo, accumulated data suggest that anesthetic drugs alter 5-HT homeostasis in the central nervous system. In an effort to identify one possible site of anesthetic action, the effect of halothane on the uptake of 5-HT was studied in synaptosomes isolated from the brain of rat. Established techniques were used to prepare the synaptosomal fractions and measure high affinity transport of radiolabelled 5-HT. Halothane inhibited synaptosomal accumulation of 5HT in a concentration-dependent manner, but had little effect on the passive or spontaneous release of the accumulated 5-HT. Rates of uptake of 5HT were inhibited by 43% in the presence of 1 mM halothane and by 75% of control in the presence of 5 mM halothane; the apparent I50 for halothane was 1.0 +/- 0.1 mM and Lineweaver-Burk analysis indicated the inhibition to be competitive at concentrations around the I50. PMID- 2304619 TI - Co-expression of alpha-CGRP and beta-CGRP mRNAs in the rat dorsal root ganglion cells. AB - We examined the expression of alpha-calcitonin gene-related peptide (alpha-CGRP) and beta-CGRP mRNAs in the rat dorsal root ganglion (DRG) using in situ hybridization histochemistry with oligonucleotide probes. Analysis of autoradiograms showed that alpha-CGRP mRNA labeled 36.4% of all DRG neurons and beta-CGRP mRNA labeled 30.8%. Small and medium-sized neurons expressed both types of mRNA, but large neurons showed a predominance of alpha-CGRP mRNA expression. The colocalization of alpha-CGRP and beta-CGRP mRNAs was shown at a cellular level in consecutive DRG sections. Thus, we demonstrated that alpha-CGRP and beta CGRP were distributed differently in the DRG neurons, although genes coding for these neuropeptides coexist in the small or medium-sized neurons. PMID- 2304620 TI - Type-specific expression of protein kinase C isozymes in CNS tumor cells. AB - We examined specific expression of protein kinase C (PK-C) isozymes in cultured human glial and neuronal cell lines, using type-specific monoclonal antibodies MC 1a, -2a, and -3a (Hidaka H. et al., J. Biol. Chem., 263 (1988) 4523-4526). Immunoblotting experiments revealed that a 80 kDa band of three kinds of glioblastoma cells (A-172, SK-MG-1, SK-MG-4) was stained with MC-3a, whereas that of neuroblastoma cells (SK-N-MC) reacted with MC-2a. Immunoenzymetric assay showed that glioblastoma cells (A-172, SK-MG-1, SK-MG-4) contained 127.6 +/- 14.4, 248.8 +/- and 148.5 +/- 35.8 ng/mg protein of type III. respectively, while neuroblastoma cells (SK-N-MC) contained 389.5 +/- 20.7 ng/mg protein of type II. These results suggest that PK-C isozymes may be specifically expressed, depending on types of central nervous system (CNS) tumor cells. PMID- 2304622 TI - Taste nerve responses during licking behavior in rats: importance of saliva in responses to sweeteners. AB - Taste responses of the rat chorda tympani nerve, innervating taste cells on the anterior part of the tongue, were recorded under awake and anesthetic conditions. Responses to licking of taste solutions in conscious animals were compared with those to taste solutions poured onto the tongue, without contamination of saliva, in anesthetized ones. The most noticeable finding was that sweet-tasting substances such as sugars and amino acids elicited larger magnitudes of neural responses (2-4 times) under awake condition than under anesthetic experimental condition. We conclude that a proper ionic composition of mucous substances covering the surface of the taste cell membrane is important in generating good responses to sweeteners as observed in licking rats. PMID- 2304621 TI - Modulation of afferent transmission to single neurons in the ventroposterior thalamus during movement in rats. AB - Single units (n = 135) were recorded in the ventroposterolateral nucleus of the thalamus in awake rats. The responsiveness of neurons to sensory activation during rest and treadmill locomotion was tested by stimulation through electrodes implanted under the skin of the forepaw. The averaged evoked unit response was suppressed by a mean 31% during movement as compared with rest. This is to be compared with the mean 71% sensory suppression observed previously in the somatosensory cortex. These findings are consistent with the hypothesis that sensory information ascending to, and within the SI cortex is successively modulated at several levels during movement. PMID- 2304623 TI - Effects of dopamine autoreceptor stimulation on the release of colocalized transmitters: in vivo release of dopamine and neurotensin from rat prefrontal cortex. AB - The in vivo release of dopamine and neurotensin from the rat medial prefrontal cortex was studied using perfusion microdialysis coupled with sensitive radioimmunoassay and HPLC techniques. Following stimulation of dopamine autoreceptors with either apomorphine (30 micrograms/kg, s.c.) or EMD-23448 (10 microM in the perfusion buffer) a decrease in dopamine and an increase in neurotensin release was observed. The release of both substances was measured in the same dialysis sample. These data suggest that activation of dopamine autoreceptors in the prefrontal cortex produces opposing effects on the release of dopamine and neurotensin. PMID- 2304624 TI - Lesions of the deep prepiriform cortex ('area tempestas') in rats do not affect the convulsant action of systemically administered bicuculline. AB - The gamma-aminobutyric acid (GABA) antagonist, bicuculline, induces generalized motor seizures when injected into a discrete site ('area tempestas') in the deep prepiriform cortex at concentrations considerably lower than those that induce convulsions from closely adjacent areas or other forebrain sites such as amygdala and hippocampus. This observation prompted the suggestion that the area tempestas is a crucial epileptogenic site involved in seizure generation. In the present study, the region functionally defined as area tempestas in rats was bilaterally destroyed by microinjection of ibotenic acid. Systemic administration of bicuculline induced generalized motor seizures in both lesioned and non-lesioned animals without any indication of differences in seizure severity or latency. This argues against the suggestion that the deep prepiriform cortex plays a crucial role in the generation of seizures following systemic administration of GABA antagonists. PMID- 2304625 TI - Indications for a hormonal function of dopamine in the central nervous system of the snail Lymnaea stagnalis. AB - In the present paper we collected evidence for the occurrence of D2-like dopamine receptors on the cell bodies of the neuroendocrine growth hormone-producing cells (GHCs) in the central nervous system (CNS) of the snail Lymnaea stagnalis. Measurements of the membrane potential of GHCs in situ as well as isolated GHCs revealed that stimulation of these dopamine receptors results in a hyperpolarization. Although immunohistochemical analysis of the CNS of L. stagnalis clearly revealed the occurrence of dopamine containing cells and nerve fibers, no projections of dopamine immunopositive fibers to the GHC cell bodies could be observed. By using HPLC with electrochemical detection we found that the blood concentration of dopamine in L. stagnalis is in the range of concentrations hyperpolarizing GHCs in vitro (0.1-10 microM). On the basis of these findings it is proposed that dopamine is involved in hormonal communication in the CNS of L. stagnalis. PMID- 2304626 TI - Gap junctions in the hypothalamic arcuate neurons of ovariectomized and estradiol treated rats. AB - Freeze-fracture methodology was used to study the organization of the neuronal plasma membrane in the rat arcuate nucleus, an estrogen sensitive area of the hypothalamus. Freeze-fracture replicas were prepared from 6 adult ovariectomized rats injected with a single dose of 17 beta-estradiol and from 6 ovariectomized littermates injected with vehicle. Rats were sacrificed 2 days after the injection. Occasional gap junctions were observed in freeze-fractured neuronal membranes from both groups of animals and their incidence was increased (P less than 0.01) in estradiol treated rats. This study demonstrates gap junctions in arcuate neurons and suggests that these structures may be affected by gonadal hormones. PMID- 2304627 TI - Sodium ions inhibit the stimulant action of caffeine on catecholamine secretion from adrenal chromaffin cells of the guinea pig. AB - Catecholamine secretion evoked by caffeine (40 mM) was markedly enhanced by replacing NaCl in the medium with sucrose or KCl in the absence, but not in the presence, of extracellular Ca2+ and Mg2+ in both perfused adrenal glands and isolated chromaffin cells of the guinea pig. The response to caffeine declined on repetition, but was restored completely after readmission of Ca2+. These results indicate that extracellular Na+ inhibits caffeine from stimulating catecholamine secretion, which may be mediated by a release of Ca2+ from intracellular storage sites in the adrenal chromaffin cells in the presence of extracellular Ca2+ and/or Mg2+. PMID- 2304628 TI - Involvement of coerulospinal noradrenergic pathway in fentanyl-induced muscular rigidity in rats. AB - Unilateral, site-specific microinjection of fentanyl (2.5 micrograms/50 nl) into the locus coeruleus (LC) in Sprague-Dawley rats anesthetized with ketamine evoked a significant increase in the electromyographic activity recorded from both caudal lateral extensor and gastrocnemius muscles. This correlate of opiate induced muscular rigidity was appreciably antagonized by a pretreatment with the specific alpha 1-adrenoceptor blocker, prazosin (250 micrograms/kg, i.v.). On the other hand, an equimolar dose (0.65 mumol/kg) of the specific alpha 2 adrenoceptor blocker, yohimbine (0.23 mg/kg, i.v.) failed to prevent the occurrence of fentanyl-induced EMG activation. We suggest that the coerulospinal noradrenergic pathway may be directly involved in the elicitation of muscular rigidity by fentanyl, possibly via alpha 1-adrenoceptors in the spinal cord. PMID- 2304629 TI - Release of calcitonin gene-related peptide induced by capsaicin in the vascularly perfused rat stomach. AB - It has been suggested that capsaicin-induced gastric mucosal protection results from the local release of vasodilator peptides such as calcitonin gene-related peptide (CGRP) from afferent nerve endings within the stomach, since CGRP is able to reduce gastric lesion formation. This concept is supported by the present finding that capsaicin (10(-5) M), administered to the vascularly perfused stomach of the rat, produces a more than 30-fold rise of the CGRP content of the venous effluent. High-pressure liquid chromatography revealed only one peak of immunoreactivity coeluting with synthetic CGRP. PMID- 2304630 TI - Decreases in tissue levels of ubiquinol-9 and -10, ascorbate and alpha-tocopherol following spinal cord impact trauma in rats. AB - Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to delayed tissue damage following traumatic spinal cord injury (SCI). Ubiquinols (reduced coenzyme Q), ascorbate (vitamin C), and alpha tocopherol (vitamin E) are endogenous antioxidants; decreases in tissue levels of these compounds may, therefore, reflect ongoing oxidative reactions. In the present studies, alterations in tissue levels of ubiquinol-9 and -10, ascorbate, and alpha-tocopherol were examined after SCI of varying severity in the rat. Levels of alpha-tocopherol did not change significantly after injury. Ascorbate and ubiquinol levels were decreased after trauma. Changes in tissue levels of ubiquinol, but not ascorbate reflected the degree of trauma. Thus, ubiquinol levels may provide a useful marker of the oxidative component of the secondary injury response. PMID- 2304631 TI - Differential effects of the protein kinase inhibitor K-252a on the in vitro survival of chick embryonic neurons. AB - The effects of the protein kinase inhibitor K-252a on the in vitro survival of different populations of chick embryonic neurons were tested. Following dissociation from the corresponding ganglia by trituration, the neurons were cultured on laminin-coated dishes in both the presence and absence of their respective neurotrophic factor. K-252a alone promoted long-term neuronal survival of dorsal root ganglion (DRG) and ciliary ganglion (CG) neurons in a dose dependent fashion. No such effect was seen with sympathetic ganglion (SG) neurons. In addition, K-252a did not interfere with nerve growth factor (NGF)- or ciliary neuronotrophic factor (CNTF)-mediated survival of DRG or CG neurons, respectively, but completely blocked the NGF- and CNTF-induced survival of SG neurons. High potassium-induced survival of SG neurons was not affected by K 252a. These results point to differences between various neuronal populations in the signal transduction mechanism for neurotrophic factors. PMID- 2304632 TI - MPTP, MPDP+ and MPP+ cause decreases in dopamine content in mouse brain slices. AB - MPTP causes a Parkinson's disease-like syndrome in which the dopamine content of the nigrostriatal system decreases. We have studied the relationship between physiological changes and dopamine content using a brain slice preparation developed for electrophysiological studies of corticostriate and nigrostriatal synaptic transmission. We report that MPTP, MPDP+ and MPP+ cause significant decreases in dopamine content of mouse brain slices. We also report that compounds (pargyline and GBR-12909) which block MPTP's toxicity in vivo and prevent non-reversible changes in synaptic transmission are not able to alter MPTP's ability to decrease slice dopamine contents. This indicates that the dopamine content in slices may not be causally related to the non-reversible decrease in synaptic transmission or in vivo neurotoxicity. PMID- 2304633 TI - Do injuries to the developing human brain alter corticospinal projections? AB - Experimental lesions of the mammalian brain involving the developing corticospinal pathways may cause these pathways to become redirected. In humans, injury to the developing brain results in disorders of movement known collectively as 'cerebral palsy'. These motor disorders differ from those produced by similar lesions in adults. We present evidence that abnormal corticospinal projections exist in subjects who have had an injury to the brain in the perinatal period. These aberrant connections, which may represent misdirected corticospinal fibers, help to explain the impairment of voluntary movements experienced by these subjects. PMID- 2304634 TI - Sensory neuropeptides in health and disease. Conference report on Florence '89. AB - A workshop (chaired by F. Lembeck, Graz) was held in Florence on 1 and 2 June 1989 with the aims to present and discuss the state of the art of research on sensory neuropeptides, i.e. those peptides demonstrated to be coded and synthetized in and released from sensory neurons. The meeting was therefore, particularly focused on tachykinins (substance P, neurokinin A and B) and calcitonin gene-related peptide (CGRP) and on the use of capsaicin as a pharmacological tool for studying the function of the related neurons. Particular relevance was paid to the biological effects and pathophysiological role(s) of sensory neuropeptides peripherally released ('efferent' function) from capsaicin sensitive primary afferents. PMID- 2304635 TI - Arborization of corticothalamic axons in the auditory thalamus of the cat: a PHA L tracing study. AB - As a result of Phaseolus vulgaris leucoagglutinin (PHA-L) injection in the primary auditory cortex of the cat, portions of corticofugal axons could be traced individually in the reticular complex of the thalamus (RE) and in the medial geniculate body (MGB). On their way to the MGB, axons were seen to give off collaterals which terminated in RE. In the MGB, an individual corticofugal axon was fully reconstructed. It ramified at 3 distinct frontal levels in the rostral half of the pars lateralis (LV). Its terminal branches gave rise to boutons en passant and terminaux in a stripe of LV (parallel to the isofrequency contours), overlapping a cluster of retrogradely labeled neurons, supporting at the microscopic level the principle of the reciprocity of thalamocortical and corticothalamic projections. PMID- 2304636 TI - Somatotopical arrangement of rat spinal dorsal horn cells processing input from deep tissues. AB - Extracellular recordings were made from 29 dorsal horn neurones which could be driven by mechanical stimulation of deep tissues, in spinal segment L4 of rats. The recording sites were marked by iontophoresis of pontamine sky blue. According to the location of the receptive fields the cells were classified as deep neurones (12 cells), which had input from deep tissues only, and as cutaneo-deep neurones (17 cells), which had receptive fields in both skin and deep tissues. The deep cells showed a correlation between the recording sites in the dorsal horn and the location of the receptive fields on the hind-limb: the more distal a deep receptive field was situated on the hind-limb the more medial was the location of the recording site in the dorsal horn. In cutaneo-deep neurones the correlation was statistically significant for the deep receptive fields but not for the cutaneous ones. PMID- 2304637 TI - Effect of the glucocorticoid milieu on the immunostaining of peptide histidine isoleucine (PHI) in the rat hypothalamus. AB - Effects of adrenalectomy (ADX) or dexamethasone (DEX) treatment on the immunostaining of hypothalamic peptide histidine isoleucine (PHI) were examined in male rats. After colchicine treatment, PHI-containing cell bodies were observed in the suprachiasmatic nucleus (SCN) and the parvocellular division of the paraventricular nucleus (PVN). ADX increased and DEX dose-dependently decreased the number of PHI-immunopositive neurons in the PVN. The number of SCN PHI neurons was not affected by any treatment employed in this study. These results suggest that PVN-PHI neurons are under the effects of the glucocorticoid milieu, and that the neurons may be involved in the glucocorticoid regulation of adrenocorticotropin and prolactin secretion. PMID- 2304638 TI - Demonstration of a medial to lateral gradient in the density of cholinergic neuropil in the rat striatum. AB - The striatum is anatomically organized into both distinctly bounded compartments (striosomes) and gradients of neuronal markers. Biochemical markers of striatal cholinergic systems are distributed in increasing amounts laterally. We have investigated the morphologic basis of this gradient by quantitative analysis of neuronal somata and neuropil stained immunocytochemically for choline acetyltransferase (ChAT). We found in both immature and adult rats that there was no difference in the density (neurons mm2) of somata in the medial and lateral compartments. In both age groups, however, there was a clear increase in ChAT positive neuropil laterally. This medial to lateral gradient was present in all striatal planes examined. This gradient corresponds to the distribution of some other, non-cholinergic, striatal biochemical markers, and is likely to represent an important organizational feature of striatal anatomy, with functional implications. PMID- 2304639 TI - Long ascending unmyelinated primary afferent axons in the rat dorsal column: immunohistochemical localizations. AB - The present study demonstrates a significant number of calcitonin gene-related peptide (CGRP) immunolabeled unmyelinated axons in the C3 fasciculus gracilis of the rat. Approximately 88% of these axons are lost following dorsal rhizotomies from midthoracic levels caudally. Assuming that CGRP labels primary afferent axons, these findings support the hypothesis that there are significant numbers of long ascending unmyelinated primary afferent axons in the dorsal columns of the rat. If these findings can be generalized, they may have clinical import. PMID- 2304640 TI - Re-innervation of rat molar tooth pulp following transection of the inferior alveolar nerve. AB - The inferior alveolar nerves (IAN) of young male Wistar rats (b.wt. greater than or equal to 200 g) were transected unilaterally, slightly proximal to the mandibular foramen under anesthesia with chloral hydrate (0.4 g/kg, i.p.). After various postoperative periods of time, the animals received horseradish peroxidase (HRP) applications to 3 mandibular molar tooth pulps on both sides and were fixed by transvascular perfusion 24 h later. Horizontal 60 microns sections of the trigeminal ganglion were incubated with tetramethylbenzidine hydrochloride and the cross-sectional areas of all the labeled neuronal cell bodies were measured. The average number of labeled cells on the untransected (control) side was 148 (n = 26), with cross-sectional areas ranging between 131.9 and 2129.6 microns 2. Of these, 42.5% fell between 300 and 600 microns 2. About 13.5% (n = 7) of the primary neurons innervating the tooth pulps escaped the ipsilateral neurotomy and were labeled by HRP application on postoperative day 0. With HRP application on postoperative day 3, the number of labeled neurons recovered to 56.8% (n = 7) that of the control and maintained this level up to postoperative day 75. From postoperative days 3 through 75, the cell size spectrum of labeled neurons on the transection side was similar to that of the control and no consistent tendency of alteration was observed; i.e. they were distributed between 134.4 and 2214.3 microns 2, with the mode being 41.5% in the range between 300 and 600 microns 2 (n = 19). PMID- 2304641 TI - Origin of sympathetic innervation of the knee joint in the cat: a retrograde tracing study with horseradish peroxidase. AB - In the cat the origin of sympathetic nerve fibers in the medial and posterior articular nerve (MAN and PAN) of the knee joint was studied using retrograde labeling with horseradish peroxidase (HRP). Three to 5 days after uptake of HRP by MAN per cat 404 +/- 136 labeled somata (mean +/- S.D., n = 4 cats) were found mainly in the paravertebral ganglia L4 and L5 of the ipsilateral sympathetic trunk, and uptake of HRP by PAN labeled per animal 532 +/- 155 cell bodies (mean +/- S.D., n = 4 cats) mainly in the paravertebral ganglia L5 and L6. The cross sectional areas of the labeled somata ranged from 200 to 1300 microns 2 with a mean of about 620 microns 2. PMID- 2304642 TI - Epileptiform activity in hippocampal slice cultures with normal inhibitory synaptic drive. AB - The synaptic events responsible for epileptiform burst discharge are often difficult to define. Blockade of inhibition has been used to produce epileptiform events, but it is unclear whether increased excitatory activity in the presence of normal inhibition can also result in burst discharge. In the hippocampal slice culture preparation, a small percentage of cultures exhibit spontaneous bursts. To determine whether the absence of inhibitory postsynaptic potentials (IPSPs) is responsible for these spontaneous bursts, we applied the glutamate antagonist, kynurenic acid (KYN) to block burst activity, and unmask any underlying IPSPs. KYN (10 mM) quickly reduced synaptic activity with concomitant loss of burst discharge. Washout of KYN resulted in a gradual return of synaptic activity, during which time both fast and slow IPSPs were clearly observed. As burst activity returned to control levels, excitatory postsynaptic potentials (EPSPs) were increasingly superimposed within the inhibitory events, obscuring (but not eliminating) the IPSPs. In these hippocampal slice cultures, therefore, epileptiform bursts appear to be the result of an abnormally high level of excitatory synaptic drive, not a reduction in inhibition. PMID- 2304643 TI - Central control of the sensory afferent terminals from a leg chordotonal organ in crayfish in vitro preparation. AB - In an in vitro preparation of the crayfish thoracic locomotor system, intracellular recordings have been performed from terminals of a leg joint coxo basipodite chordotonal organ (CB). In the terminals, some depolarizing events are observed which display all the characteristics of the primary afferent depolarizations (PADs). PADs reduce the amplitude of orthodromic sensory spikes, and thus correspond to a presynaptic inhibition. PADs are tonic in a tonic preparation, and phasic (phase locked) in a rhythmic preparation. A control of the incoming information from the CB could thus be performed by the central nervous system during fictive locomotion. PMID- 2304644 TI - Vestibular and visual signals in the ventral paraflocculus of the cerebellum in rabbits. AB - Extracellular microelectrode recordings from single cerebellar neurons were made in the ventral paraflocculus of anesthetized, paralyzed pigmented rabbits during vestibular and visual stimulation. The discharge of 6 out of 207 neurons was modulated during vestibular or visual stimulation. The activity of 5 neurons was modulated during vertical vestibular stimulation. The discharge of only one neuron was modulated exclusively during vertical optokinetic stimulation. The information from both the vestibular and visual systems which is received by the ventral paraflocculus appears to differ from that which is received by the flocculus in rabbits. PMID- 2304645 TI - Neuropeptide Y-immunoreactive synapses in the intermediolateral cell column of rat and rabbit thoracic spinal cord. AB - Neuropeptide Y (NPY)-immunoreactive nerve fibers in the intermediolateral cell column of rat spinal cord segments T2-T3 and T8-T10 and rabbit segments T3-T6 were studied with light and electron microscopic immunocytochemistry. Plexuses of NPY-immunoreactive nerve fibers were found by light microscopy. NPY-positive synapses were present electron microscopically but non-immunoreactive synapses greatly outnumbered NPY-immunoreactive ones. In the lateral horn of rat T9, 30% of the vesicle-containing NPY-positive axon profiles formed synapses, 95% of which were axodendritic. These synaptic connections may mediate the effects of brainstem NPY neurons on the activity of sympathetic preganglionic neurons. PMID- 2304646 TI - Electrophysiological evidence for visual-vestibular interaction in man. AB - The aim of the experiments reported here was to confirm electrophysiologically the results of psychophysical experiments, which demonstrated that thresholds for object-motion detection are significantly raised during both concurrent active or passive sinusoidal head oscillations and during visually induced self-motion perception (circularvection, CV). This intersensory inhibition could now be demonstrated electrophysiologically by recording visual motion evoked potentials both during concurrent sinusoidal head oscillations and during visually induced apparent self-motion of the objectively stationary subject. Recordings of visual contrast reversal evoked potentials failed to reveal such an interaction. Perceptual phenomena with multisensory stimulation are well described in the literature. Berthoz et al. demonstrated the dominant influence of the visual channel on vestibular thresholds such that the detection of a suprathreshold vestibular stimulation was clearly impaired by a simultaneously moving visual pattern inducing linearvection and vice versa. Comparable results are reported for circularvection. Evidence for inhibitory interaction between object-motion and simultaneous self-motion perception also exists. Electrophysiological data on intersensory interaction in humans have only been reported between electrical stimulation of a limb and its concurrent movement by means of scalp-recorded somatosensory-evoked potentials (SSEPs) (e.g. refs. 3, 5). Electrophysiological evidence for the interaction of visual object-motion and vestibular self-motion perception in humans has never been reported in the literature thus far, though Hood and Kayan demonstrated that retinal image motion makes a contribution to the vestibularly evoked bioelectric response. PMID- 2304647 TI - The influence of different light intensities on pineal melatonin content in the retinal degenerate C3H mouse and the normal CBA mouse. AB - The sensitivity of light-induced suppression of pineal melatonin content was compared between C3H mice with hereditary retinal degeneration and CBA mice with normal retinas. At 2 h before lights on of light-dark (LD) cycles, when pineal melatonin content is the highest in both strains, groups of mice were exposed to different intensities of white fluorescent light (100, 0.14, 0.017 lux in both strains and 0.0021 and 0.00026 lux in CBA mice). For each intensity, pineals were collected just before and 5, 15 and 30 min after exposure to light. In C3H mice, the threshold of light intensity to suppress pineal melatonin content was between 0.14 and 0.017 lux, whereas that in CBA mice was between 0.0021 and 0.00026 lux. These results suggest that both rods and cones mediate photic information to the pineal gland in mice. PMID- 2304648 TI - Presynaptic M1 muscarinic cholinoceptors mediate inhibition of excitatory synaptic transmission in the hippocampus in vitro. AB - The effects of the cholinoceptor agonist, carbachol (CCh), were examined in the rat hippocampal slice preparation. Intracellular recordings from CA1 pyramidal neurones revealed that CCh (1-3 microM) inhibited excitatory postsynaptic responses evoked by stimulation of the Schaffer collateral/commissural pathway while, at the same time, direct excitability was enhanced. Extracellularly, CCh produced a concentration-dependent reduction of the amplitude of the field excitatory postsynaptic potential (field EPSP) recorded in the CA1 apical dendritic region. The muscarinic receptor antagonist, pirenzepine, competitively antagonized the effects of CCh on the field EPSP with a pA2 of 7.4. These results confirm earlier reports of a presynaptic inhibitory action of CCh in the hippocampal CA1 region and provide strong evidence that this effect is mediated by muscarinic receptors of the M1 subtype. PMID- 2304649 TI - Increased spectrin proteolysis in the brindled mouse brain. AB - Proteolytically generated fragments of the microfilament anchoring protein brain spectrin were found to accumulate in brindled mouse brain. Proteolysis was most extensive in brain regions possessing high concentrations of N-methyl-D-aspartate (NMDA) receptors (e.g. cortex, striatum, hippocampus). The brindle mutation affects copper homeostasis and thus a variety of copper-dependent enzymes needed in intermediary metabolism. The altered mitochondria of these mice are suggested to less efficiently buffer NMDA receptor-gated calcium fluxes, thus promoting activation of calcium-activated proteases and subsequent degradation of the spectrin meshwork. PMID- 2304650 TI - Rat dorsal root ganglion neurons in culture express vasoactive intestinal polypeptide (VIP) independently of nerve growth factor. AB - Expression of vasoactive intestinal polypeptide (VIP) was studied in regenerating adult rat dorsal root ganglion (DRG) neurons in culture. VIP was not detected by radioimmunoassay in newly established cultures but increasing concentrations were observed between 2 and 4 days and VIP remained detectable for more than 2 weeks. Immunocytochemical staining revealed VIP-like immunoreactivity in virtually all neurons. Thus, VIP is expressed in regenerating DRG neurons in culture just as it is in vivo following axotomy. However, VIP concentrations in culture were the same whether nerve growth factor was present or not. Therefore, deprivation of retrogradely transported nerve growth factor is unlikely to explain VIP induction by axotomy in vivo. PMID- 2304651 TI - Effect of methionine sulfoximine on pyruvate dehydrogenase, citric acid cycle enzymes and aminotransferases in the subcellular fractions isolated from rat cerebral cortex. AB - The effect of acute and subacute doses of L-methionine-DL-sulfoximine (MSI) were studied on the activities of pyruvate dehydrogenase, enzymes of citric acid cycle and aspartate and alanine aminotransferases in the mitochondria, synaptosomes and cytosol of rat brain. In general, the activities of pyruvate dehydrogenase and of the citric acid cycle enzymes, except malate dehydrogenase (malate--- oxaloacetate), were elevated in all 3 subcellular fractions. Malate dehydrogenase activity (malate----oxaloacetate) was suppressed in the mitochondria while the activity of this enzyme in the reverse direction was enhanced in the cytosol. Activities of aspartate and alanine aminotransferases were suppressed under these conditions. As the effects of MSI on these enzymes were similar to those observed upon the administration of ammonium salts, it is suggested that the hyperammonemic state induced by MSI might derange the operation of the malate aspartate shuttle. Increased activities of citric acid cycle enzymes in the cytosol suggested the existence of a small population of mitochondria which was highly vulnerable either to ammonia or to MSI. PMID- 2304652 TI - MPTP toxicity in the mouse brain and vitamin E. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused transient alterations in vitamin E levels in every brain region examined. However, vitamin E returned to normal levels within a few hours in all brain regions but the substantia nigra, where at 2 days vitamin E levels first rose above normal levels. Vitamin E deficient mice were much more susceptible to MPTP toxicity than controls, in terms of lethality and DOPAC depletion in the substantia nigra. However, in the same vitamin E deficient mice, the striatum was partially protected from neurotransmitter and metabolite depletion by MPTP. The mechanism of toxicity of MPTP may differ in the striatum and the midbrain. PMID- 2304653 TI - Serum levels of interleukin-6 are not elevated in patients with Alzheimer's disease. AB - Serum levels of interleukin-6 (IL-6) were determined in 97 patients with clinically diagnosed Alzheimer's disease and 79 age- and sex-matched control subject. Median serum levels of IL-6 did not differ significantly between Alzheimer patients (8.6 U/ml) and controls (8.2 U/ml). Median levels of serum IL 6 were similar for sporadic and familial patients. The concentration of IL-6 was not associated with the severity of the dementia or the duration of the disease since first symptoms. According to these observations there is no evidence for a significant elevation in serum IL-6 in Alzheimer's disease. PMID- 2304654 TI - What do we know about the mechanism of weight loss in AIDS? PMID- 2304655 TI - Buriti: a rich natural source of provitamin A for the treatment of xerophthalmia in Brazil. PMID- 2304656 TI - Metabolic effects of carnitine supplementation in subjects with low plasma carnitine levels. PMID- 2304657 TI - Use of vitamin and mineral supplements in the United States. PMID- 2304658 TI - Esterification of all-trans-retinol and its isomerization to 11-cis-retinol. PMID- 2304659 TI - The health and health care challenges for New York City in the 1990s. PMID- 2304660 TI - Bile duct carcinoma. PMID- 2304661 TI - An intervention to reduce the sale of cigarettes to minors. AB - This study reports the results of an intervention to stop the illegal sale of cigarettes to minors. Sixty-two of 120 stores in Erie County, New York, were randomly selected to receive in the mail an informational packet requesting their help in stopping the illegal sale of tobacco to minors. The packet included a letter to the store manager citing the law prohibiting the sale of tobacco products to minors and requesting their assistance in observing the law; a supply of warning signs; and a tip sheet designed to assist store managers in educating their employees about the law. Two weeks after the mailing, stores in the study were visited by study teenagers aged 14 to 16 who attempted to purchase cigarettes. The intervention resulted in an increased number of stores posting warning signs, but had no effect on deterring the sale of cigarettes to minors. Minors purchased cigarettes in 77% of stores that received the special mailing and in 86% of nonintervention stores. Warning signs were visible in 40% of stores that received the special mailing and in none of the nonintervention stores. The findings from this study suggest that a merchant education program to increase awareness of the law and posting of warning signs is not sufficient to discourage the sale of tobacco products to minors. PMID- 2304662 TI - Assessing the damage from cigarette smoking in New York State. AB - Although there is clear evidence that smoking is the leading preventable cause of death in the United States today, almost one third of American adults continue to smoke. To promote public awareness of smoking's adverse effects, we applied a previously established methodology to estimate the impact of cigarette smoking in New York State. Using New York State-specific mortality data, cigarette smoking prevalence rates, and total health care costs, we found that cigarette smoking caused almost 27,000 deaths in 1985, resulting in 335,000 years of potential life lost (mean, 12 years per person). The estimated annual cost of smoking totaled +4.7 billion, including direct (health care) and indirect (lost income and productivity) costs from smoking-attributable deaths and illness. The New York State Department of Health publicized these findings to gain support for a statewide regulation for smoking control in public places. This methodology can easily be applied elsewhere to assess the adverse impact of smoking and to support smoking control activities. PMID- 2304663 TI - The Alaskan community health aide scheme. A successful rural health program. PMID- 2304664 TI - Bile duct carcinoma simulating choledocholithiasis. PMID- 2304665 TI - Carcinoma of the colon associated with systemic sclerosis. PMID- 2304666 TI - Physician recredentialing. PMID- 2304668 TI - Eliminating the requirement for medical libraries in hospitals. PMID- 2304667 TI - Student participation in mixed gender sports competition. PMID- 2304669 TI - Gallstone appendicitis. PMID- 2304670 TI - Open supramalleolar amputation of the infected foot: an underutilized, two-stage procedure. PMID- 2304671 TI - Mortality in a follow up study of 616 alcoholics admitted to an inpatient alcoholism clinic 1972-76. AB - Six hundred and sixteen alcoholics were admitted to an inpatient alcoholism clinic (Mahu clinic, Sunnyside Hospital, Christchurch) between 1972 and 1976. The national register of deaths was searched for deaths of these patients up until 30 September 1983. Eighty-three deaths were recorded which, when compared with the general population, matched for age and sex, yielded a standardised mortality ratio of 1.6, that is 60% higher than expected. However because the patients were nearly all under 65 years of age the absolute death rate was not high--98% survived one year and 86% survived ten years. Similarly the excess death rate was quite low at 6 extra deaths per 1000 alcoholic years. PMID- 2304672 TI - The politics of cholesterol lowering drugs. PMID- 2304674 TI - Passive smoking in New Zealand. PMID- 2304673 TI - Misconceptions about cholesterol. PMID- 2304675 TI - Unconditional love and forgiveness skills in action. PMID- 2304676 TI - Prescribing of fenoterol and severity of asthma. PMID- 2304677 TI - Review committee on medical education. PMID- 2304678 TI - Guidelines for treating hypertension. PMID- 2304679 TI - Arson and psychiatry: the candles are out--or are they? PMID- 2304680 TI - Five minute psychiatric diagnostic formulation--does it have a place in general practitioner registrar training? PMID- 2304681 TI - The safety of buprenorphine (Temgesic) PMID- 2304682 TI - Medical insurance and childhood general practitioners contacts. PMID- 2304683 TI - Unsafe home births. PMID- 2304684 TI - A solar erythemal radiation monitoring programme in New Zealand and Queensland, Australia. AB - Solar erythemal radiation dose measurements carried out at five locations in Australasia from 43 degrees S to 19 degrees S during the southern summer of 1984 85 are reported. Monthly erythemal doses at the New Zealand sites reached a maximum of 8 x 10(4) joules/m2 for January and February 1985. During February 1985 this dose was the same as that measured at Townsville, Queensland, and slightly greater than the 7.3 x 10(4) joules/m2 at Rockhampton, Queensland. These results highlight the difficulty of calculating levels of solar erythemal radiation based on the latitude of the site because of local variations in cloud cover patterns. PMID- 2304685 TI - Effects of age and sex on bone density at the hip and spine in a normal Caucasian New Zealand population. AB - We have studied a normal adult caucasian population (462 females, 264 males age range 20-84) using dual photon absorptiometry to establish patterns of bone reduction at the spine and hip. Subjects were either randomly selected from the electoral roll or volunteers. Bone mineral density reduction at the lumbar spine in females appeared to increase at 40 years and was sustained until 60 years. In males bone mineral density at the spine was preserved. The density at the hip in females decreased throughout adult life beginning before the menopause. In males bone density was preserved at the femoral neck and trochanteric region but not at Wards triangle where reduction occurred throughout life. When compared with other normal populations there was higher bone mineral density at the spine in postmenopausal New Zealand females but no significant difference at the hip. PMID- 2304686 TI - The overnight thermal environment of infants. AB - Thirty healthy infants between nine and 19 weeks each had skin and room temperature monitored continuously for a single night. A simultaneous assessment of the insulating quality of the infants bedding was made. The maximum infant skin temperature noted was 37.4 degrees C, the room temperatures ranged from 10.9 degrees C to 26.2 degrees C over all study infants. The insulation score ranged from 17 to 68, with the mean 33 (SD, 13). There was a highly significant correlation between insulation score and maximum infant temperature. A significant inverse correlation between insulation score and outside temperature was noted, but not between insulation score and room temperature. These findings indicate that some infants are inappropriately overdressed for their environmental temperature. PMID- 2304687 TI - Diagnosis and the polymerase chain reaction. PMID- 2304688 TI - Simvastatin therapy for hypercholesterolaemia in patients with coronary heart disease. AB - The efficacy of simvastatin therapy for hypercholesterolaemia was evaluated in 26 patients with coronary heart disease, 20 of whom had undergone coronary artery bypass grafting. Simvastatin reduced total- and low-density lipoprotein (LDL) cholesterol from 8.3 to 5.1 (38%) and 6.3 to 3.3 mmol/L (48%) respectively, p less than 0.001; high-density lipoprotein (HDL) cholesterol increased from 1.19 to 1.24 mmol/L, p = NS. The changes in apoproteins A1 and B paralleled those of HDL- and LDL-cholesterol. There were no clinically important adverse effects. We conclude that simvastatin is effective lipid lowering therapy and can be used safely, in the short term, in patients with coronary heart disease. PMID- 2304689 TI - Inhaler devices and the elderly. AB - This study compared the relative ease of use of the metered dose inhaler, the FO2 Inhalator and the Diskhaler by elderly subjects in a randomised cross over trial using placebo inhalants. Thirty-one nonasthmatic volunteers (average age 79.6 years) who lived independently in two residential homes for the elderly were recruited. One failed to complete the study. Subjects were taught to use the three inhaler devices in a randomly assigned sequence with a two week period elapsing between each training session. The Diskhaler device took longest to learn (16.5 minutes) and the Inhalator was significantly easier to learn to use than the other two (x2 = 40.3, p = 0.001). The Inhalator was preferred by 64%, metered dose inhaler by 25% and Diskhaler by 11% (p = 0.03). Problems in the use of each are described. The study found that the Inhalator was simple to use and was reliably self administered by older people. The metered dose inhaler was simple to use only for a minority who could accurately coordinate actuation and inhalation. The Diskhaler had no advantages in this age group. PMID- 2304690 TI - Unemployment and the public health. PMID- 2304691 TI - Morphine syringes--a question of sterility. PMID- 2304692 TI - Problems in primary health care. PMID- 2304693 TI - Sandflies. PMID- 2304694 TI - Metal fume fever. PMID- 2304695 TI - The treaty of Waitangi. PMID- 2304696 TI - Transient cortical blindness in a severe preeclamptic. PMID- 2304697 TI - Anaemia in Maori infants--a persisting problem. PMID- 2304699 TI - Asthma, inhalers, and technique. PMID- 2304698 TI - Passive smoking. PMID- 2304700 TI - Library resources in rheumatic diseases. PMID- 2304701 TI - Mitoxantrone induced hyperpigmentation. PMID- 2304703 TI - Abnormal karyotype of fetuses with omphalocele: prediction based on omphalocele contents. AB - The majority of fetuses with omphalocele have other congenital abnormalities and, in many cases, an abnormal karyotype. We retrospectively studied 22 consecutive fetuses with sonographically diagnosed omphalocele and available karyotype to determine whether the contents of the omphalocele could predict the karyotype. Of these 22 fetuses, 18 had normal and four had abnormal karyotypes. Sixteen of the karyotypically normal fetuses had liver herniated into the omphalocele and two had only bowel present in the defect. All four of the fetuses with abnormal chromosomes had only bowel in the defect. PMID- 2304702 TI - An ethically justified, clinically comprehensive management strategy for third trimester pregnancies complicated by fetal anomalies. AB - We present an ethically justified, clinically comprehensive management strategy for third-trimester pregnancies complicated by fetal anomalies, based on 72 cases diagnosed at a gestational age of more than 24 weeks. These cases are organized into three categories: A) nonaggressive management and termination of pregnancy offered, three of 72 (4%); B) aggressive and nonaggressive management offered, 18 of 72 (25%); and C) aggressive management recommended, 51 of 72 (71%). We then ethically justify a clinically comprehensive management strategy. First, we describe the disclosure requirements of the informed-consent process. Second, we provide an ethical justification for the physician's recommendations among management alternatives. The justification for such recommendations is based on a continuum of beneficence-based obligations to the fetus that is developed in terms of a classification scheme of fetal anomalies, based on the degree of probability of antenatal diagnosis and degree of probability of outcome. When there are no beneficence-based obligations to the fetus, the physician should recommend only termination of pregnancy or nonaggressive management. When there are minimal beneficence-based obligations to the fetus, only aggressive or nonaggressive management should be recommended. Finally, when there are more than minimal beneficence-based obligations to the fetus, only aggressive management should be recommended. PMID- 2304704 TI - Placental transfer of vitamin K1 in preterm pregnancy. AB - Seventy-eight women at earlier than 35 weeks' gestation with premature rupture of membranes and/or preterm labor were randomly assigned to receive either 10 mg vitamin K1 intramuscularly (IM) or no treatment. If delivery did not occur within 4 days, the dose of vitamin K1 was repeated. Women whose pregnancies continued beyond 8 days received 20 mg of vitamin K1 orally every day until the end of the 34th week or until delivery, whichever occurred earlier. The median maternal plasma vitamin K1 level was significantly higher in treated than in untreated subjects (11.592 versus 0.102 ng/mL; P less than .001). The median cord plasma levels were 0.024 ng/mL in the treated group and 0.010 ng/mL in the controls, a significant difference (P = .046). Median plasma vitamin K1 levels were comparable in mothers receiving the drug by the IM route only and by both the IM and oral routes (10.533 versus 11.928 ng/mL; P = .460). The infants of the latter group, however, had significantly higher median cord plasma levels (0.42 versus 0.017 ng/mL; P less than .001). There was no correlation between cord plasma vitamin K1 levels and gestational age or duration of maternal supplementation with vitamin K1. We conclude that, in preterm pregnancies, vitamin K1 crosses the placenta slowly and to a limited degree. PMID- 2304705 TI - Ferning of amniotic fluid contaminated with blood. AB - The diagnosis of rupture of the membranes by traditional methods of nitrazine paper determination and fern crystallization has been reported to be 93-98% accurate. Although the presence of contaminants in amniotic fluid has been reported to reduce this accuracy, the literature is conflicting concerning these effects. We examined the effect of blood contamination on the accuracy of diagnosing ruptured membranes. Amniotic fluid was obtained from 38 patients between 16-38 weeks' gestational age who underwent amniocentesis. Amniotic fluid was immediately mixed with freshly obtained, heparinized fetal cord blood in varying concentrations (blood to amniotic fluid 1:5, 1:10, 1:20). The slides were examined microscopically for the presence of ferning. All samples were fern positive, but many had atypical ferns described as "skeletonized." As the concentration of blood to amniotic fluid increased, the number of atypical ferns increased (32 of 38 at 1:5, 22 of 38 at 1:10, and nine of 38 at 1:20). We conclude that the presence of blood may alter the morphology of the fern, but does not act as a contaminant that would affect the accuracy of the test. PMID- 2304706 TI - Labor patterns in women with previous cesareans. AB - Little information exists to help determine the presence or significance of labor abnormalities in women attempting vaginal birth after previous cesarean. A case control study was performed to obtain information on patterns of labor progress and the incidence of dysfunctional labor in patients having a trial of labor after previous cesarean delivery. Sixty-eight such women were matched to nulliparous and multiparous controls. Labor-curve characteristics for the group of women with previous cesarean differed significantly from those of both the nulliparas and multiparas. When stratified by history of previous vaginal birth, however, those with no previous vaginal birth were indistinguishable from nulliparous controls and those with a previous vaginal birth were indistinguishable from multiparous controls. Parity-specific criteria for the diagnosis of dysfunctional labor were thus indicated. Labor disorders were present most frequently in the previous-cesarean group with no previous vaginal birth (41.9%). This incidence did not differ significantly from that in the control nulliparas (27.1%) (P = .15), but did differ from that in the multiparas (15.8%) (P less than .01). Previous-cesarean patients with a previous vaginal birth had a frequency of labor disorders (14.3%) not significantly different from that of multiparous controls. We conclude that trial of labor in women with a previous cesarean should be evaluated by standard criteria for nulliparas if there has been no previous vaginal birth, and by criteria for multiparous women if there has been any previous infant born vaginally. PMID- 2304707 TI - Oxytocin use after previous cesarean: why a higher rate of failed labor trial? AB - When used for patients undergoing trial of labor after previous cesarean, oxytocin is associated with an increased failure rate. Previous reports have not studied why this occurs. From October 1984 to April 1986, 237 patients with previous cesareans underwent a trial of labor. The delivery outcomes of 73 women who received oxytocin were compared with those of the 164 who did not. Rates were similar for uterine scar dehiscence, uterine rupture, operative vaginal delivery, blood transfusions, endometritis, and low Apgar scores. Successful trial of labor occurred in 68% in the oxytocin group, compared with 89% in the no-oxytocin group. Failed trial of labor was significantly more frequent in patients who received oxytocin for induction of labor than in those who did not. When subjects who received oxytocin were divided into induction (N = 47) and augmentation (N = 26) groups, successful trial of labor occurred in 58% of the former group versus 88% of the latter group. Other characteristics of the augmentation group were spontaneous labor, greater cervical dilation and effacement at initiation of oxytocin, shorter duration of infusion, and lower oxytocin infusion rates. For patients who have had previous cesareans and who desire trial of labor, oxytocin by controlled infusion is safe. Successful trial of labor may be enhanced by awaiting spontaneous labor or inducing with a favorable cervix. PMID- 2304708 TI - The cesarean delivery rate can be safely reduced in a developing country. AB - In an attempt to reduce the cesarean rate without adverse effect on outcome, new guidelines for the management of dystocia, previous cesarean delivery, fetal distress, and breech presentation were introduced in September 1984 in a provincial hospital in Zimbabwe, Africa. Comparison of the 2-year periods before and after September 1984 showed that the cesarean rate had dropped from 16.8 to 8.0%, the maternal mortality rate from 202 to 57 per 100,000 births, and the perinatal mortality rate from 71.9 to 56.2 per 1000 births. During the latter period, use of oxytocin increased from 3.4 to 17.4%. These findings suggest that the adoption of strict guidelines can lead to a decrease in the cesarean rate and an improvement in obstetric outcome. PMID- 2304709 TI - Influence of dietary zinc and iron on zinc retention in pregnant rhesus monkeys and their infants. AB - To test the idea that zinc uptake may be enhanced in conditions of zinc deficiency, we fed rhesus monkeys diets containing either 4 micrograms zinc (low zinc group) or 100 micrograms zinc (controls) throughout pregnancy and lactation. Each group was divided into two subgroups, one of which received an iron supplement (4 mg ferrous sulfate/kg/day). We investigated iron supplements because excess dietary iron has been suggested to inhibit zinc absorption. 65Zn retention from labeled meals was studied in the dams during pregnancy and lactation and in their 10-day-old infants. In both the mothers and the infants, zinc absorption/retention, as measured by whole-body counting, was more than 25% higher in the low-zinc group than in the controls. Iron supplementation had no effect on initial dietary zinc retention, but resulted in a reduction in whole body 65Zn turnover. Thus, changes in zinc status and dietary factors such as iron can affect net retention and turnover of zinc in pregnant and lactating primates fed low-zinc diets. PMID- 2304710 TI - The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy. AB - Thirty-three gravidas with syphilis were monitored with hourly vital signs and examinations for 24 hours after treatment with benzathine penicillin G. Fifteen (45%) of the subjects had a Jarisch-Herxheimer reaction, including all three, 12 of 20 (60%), and none of ten of those with primary, secondary, and latent syphilis, respectively. The most common symptoms were fever (73%), uterine contractions (67%), and decreased fetal movement (67%). The signs or symptoms began 2-8 hours after treatment; fevers peaked at 6-12 hours post-therapy and the events usually abated by 16-24 hours after treatment. Uterine contractions and decreased fetal activity began concurrent with maternal fever in eight of ten women reporting contractions. Transient late decelerations were detected in three of 11 monitored patients. Three of the women with Jarisch-Herxheimer reactions delivered infants with congenital syphilis, including one stillbirth, but none of those without a detectable reaction had fetal treatment failures. Prostaglandin F2 alpha and prostacyclin metabolites were elevated transiently in the one subject studied, suggesting their role in mediating the cardiovascular and uterine events in the post-treatment period. The Jarisch-Herxheimer reaction in pregnancy is similar in frequency, character, and intensity to that in nonpregnant adults, but gravidas may have increase uterine activity and transient alterations in fetal well-being. The pregnant patient with a severely affected fetus with congenital syphilis may experience preterm labor, preterm delivery, or fetal death in association with the Jarisch-Herxheimer reaction. PMID- 2304711 TI - The persistence of abnormal glucose tolerance after delivery. AB - In the first 7 days after delivery, 270 women who had gestational diabetes and 100 who had normal prenatal glucose tolerance were retested for glucose intolerance. In the group who had gestational diabetes, glucose tolerance remained abnormal by the Mercy Maternity Hospital criterion in 28% of those who had been delivered vaginally and in 43% of those delivered by cesarean. The only abnormal test in the control group was in one of the two women delivered by cesarean, and this test returned to normal by the seventh postoperative day. By 6 weeks postpartum, the incidence of abnormal glucose tolerance was 24 and 30% for patients having vaginal and abdominal deliveries, respectively. The method of infant feeding had no significant influence on the prevalence of abnormal glucose tolerance. We conclude that if a glucose tolerance test has not been performed prenatally, the test is still worthwhile in the immediate puerperium if the possibility of gestational diabetes has been raised by adverse pregnancy outcome, because about one in three diabetics will be thus identified. However, screening in the puerperium is not a substitute for prenatal screening. PMID- 2304712 TI - Demographic and historic variables in women with idiopathic chronic pelvic pain. AB - A comprehensive historic, demographic, and medical questionnaire was administered to 106 women referred to a multidisciplinary clinic for evaluation of idiopathic chronic pelvic pain and to 92 age-matched, pain-free control patients presenting for routine annual examination. Although racial distribution, mean gravidity and parity, and rates of elective abortion were similar in both groups of respondents, spontaneous abortion was reported significantly more frequently among women with pelvic pain. Patients in the study group were also more likely to be on active military duty, to have undergone previous nongynecologic surgery, and to have sought treatment for unrelated somatic complaints. Finally, although the mean ages at first intercourse were similar, women with idiopathic pelvic pain reported a higher total number of sexual partners and were significantly more likely to have experienced previous significant psychosexual trauma. These findings confirm that predisposing psychosocial variables are important in the pathogenesis of idiopathic pelvic pain and emphasize the significance of multidisciplinary evaluation and management. PMID- 2304713 TI - The prevalence of dyspareunia. AB - A questionnaire regarding sexual experience and dyspareunia was sent to 428 women, of whom 324 (75.7%) responded. Ten refused to participate and one had never had heterosexual intercourse, leaving 313 evaluable responders. One hundred twenty-two (39.0%) had never had dyspareunia and 86 (27.5%) had had dyspareunia at some point in their lives which resolved, either spontaneously or with specific treatment. One hundred five women (33.5%) still had dyspareunia at the time of the survey, 51 of whom had had dyspareunia for their entire active sexual lives. Twenty-two (21%) rarely had dyspareunia, 58 (55.2%) occasionally had discomfort, and 25 (23.8%) had dyspareunia frequently or virtually all the time. Frequency of intercourse was not different among any of the groups analyzed, although 49 (48.0%) of the women reported a decrease in sexual frequency and 35 (33.7%) reported an important adverse effect on their relationships as a result of dyspareunia. Most of the women had not discussed their dyspareunia with a health care professional and were unaware of the cause of their problem. PMID- 2304714 TI - Endometrium of cavitary rudimentary horns in unicornuate uteri. AB - The rudimentary horns removed from ten patients with unicornuate uterus, subclass A1b, were studied by light and scanning electron microscopy. Seven of the horns removed were small in volume (range 7.5-15.7 mL) and three were larger (range 20.8-39.7 mL). In four cases the endometrial cavity communicated with the tubal lumen, hematometra was present in three cases, and endometriosis was diagnosed in six. In six of the seven rudimentary horns without hematometra, the endometrial mucosa did not correspond to the cycle phase of the endometrium of the hemiuterus; however, in the three rudimentary horns with hematometra, the endometrium presented cycle-phase characteristics similar to those of the hemiuterus. The endometrio-myometrial junction, the underlying myometrium, and the arcuate arterioles were always altered. We consider that the absence of cyclic changes in the endometria of the smaller horns may be attributed to reduced vascular supply, to the absence of any isthmocervical structure, and to the qualitative and/or quantitative differences in endometrial mucosal receptors. PMID- 2304715 TI - Uterine perforation during second-trimester abortion by cervical dilation and instrumental extraction: a review of 15 cases. AB - Review of the records of 15 women who had uterine perforations at the time of second-trimester abortion by dilation and evacuation showed that unexpected pain (but not excessive bleeding) was the most prominent sign. All patients required laparotomy, but in no case was laparotomy necessary as an emergency procedure. Laparoscopy was not helpful. Two-thirds had bowel injuries and two required hysterectomy. Errors in estimating gestational duration, inadequate cervical dilation, and failure to use sonography characterized these complicated cases. PMID- 2304717 TI - Patch procedure: modified transvaginal fascia lata sling for recurrent or severe stress urinary incontinence. AB - Ten patients with either recurrent or severe stress urinary incontinence were treated with a new procedure, using a patch of fascia lata to support the bladder base and the urethra. Nine of the ten patients are objectively continent of urine 1-2 years postoperatively. When pre- and postoperative urodynamics were compared, we noted significant increases in urethral closure pressure, functional urethral length, and abdominal pressure transmission to the proximal urethra. Intraoperative and postoperative morbidity was minimal. The procedure is easily performed and requires no more expertise than does a transvaginal needle bladder neck suspension. PMID- 2304716 TI - Screening for cervical cancer in emergency centers and sexually transmitted disease clinics. AB - Low-income women are at increased risk of developing cervical cancer compared with middle- and upper-income women. How can poor women be reached for screening and early diagnosis of cervical cancer and its precursor stages? One answer to this question is based on the observation that a high percentage of the unscreened population has received some form of medical care within the previous 5 years. Emergency centers and sexually transmitted disease (STD) clinics often provide such care to patients who lack a regular source of health care. Thus, they represent potential resources for cervical cancer screening. However, in a survey of 19 hospitals whose patient populations include a high proportion of low income patients, only five reported a protocol for cervical cancer screening in their emergency centers. Similarly, all 11 STD clinics included in this survey reported that fewer than 5% of their female patients had a Papanicolaou smear taken even though virtually all of them received a pelvic examination. Based on these findings, it appears that health care administrators and policymakers could intensify their cancer prevention programs by mobilizing these resources for cancer control. PMID- 2304718 TI - Fetal heart rate monitoring at home and transmission by telephone. AB - We assessed the feasibility of introducing a home fetal heart rate monitoring system into a tertiary care perinatal unit. In the first stage of the study, 38 hospitalized high-risk pregnant patients recorded nonstress tests (NSTs) in their rooms in the hospital and transmitted the data to the receiving unit via the telephone. In the second stage, 34 women accomplished home monitoring in addition to the regular in-hospital NSTs prescribed by their physicians. The total of 72 patients, whose gestations ranged from 29-43 weeks, attempted 307 recordings, of which 93% were transmitted successfully. Ninety-eight percent of the received NSTs were considered interpretable. Based on our results, it seems that the use of the home fetal monitor by the patient in conjunction with all of the other components of a tertiary perinatal care center is feasible, reliable, and safe. PMID- 2304719 TI - Antenatal and intrapartum factors associated with the occurrence of seizures in the term infant. PMID- 2304720 TI - Tubal pregnancy with normal hysterosalpingogram and negative serum pregnancy test. AB - A patient undergoing evaluation for primary infertility with regular menses had a normal hysterosalpingogram in the follicular phase and underwent diagnostic laparoscopy the next day, with the finding of a tubal pregnancy. The patient had a negative serum pregnancy test. Although a normal hysterosalpingogram and negative serum pregnancy test are each rare with a tubal pregnancy, the combination of the two occurring in a tubal pregnancy is previously unreported and did not exclude the diagnosis in this case. PMID- 2304721 TI - First-trimester diagnosis of fetal congenital heart disease by transvaginal two dimensional and Doppler echocardiography. AB - Until recently, prenatal diagnosis of fetal cardiac malformations was restricted to the second and third trimesters. With the advent of high-frequency transvaginal probes, earlier detection of such malformations is possible. We present a case of nonimmune hydrops fetalis with complete atrioventricular canal defect, insufficiency of atrioventricular valves, and complete heart block at 11 weeks' gestation diagnosed by transvaginal two-dimensional and Doppler echocardiography. PMID- 2304722 TI - Selective embryocide in the nonsurgical management of combined intrauterine extrauterine pregnancy. AB - Early diagnosis of ectopic pregnancy has provided the opportunity for nonsurgical management in selected cases. We used selective embryocide to manage the ectopic embryo in a patient with a combined intrauterine-extrauterine gestation following in vitro fertilization. The intrauterine pregnancy continued to term without incident. PMID- 2304723 TI - Metabolic control of von Gierke disease (glycogen storage disease type Ia) in pregnancy: maintenance of euglycemia with cornstarch. AB - In patients with glycogen storage disease type Ia, glucose-6-phosphatase deficiency reduces the liver's ability to generate free glucose from glycogen. Without a continuous, exogenous source of glucose, severe hypoglycemia and subsequent metabolic perturbations occur. Our observations of a patient with glycogen storage disease type Ia, who also had a clomiphene-induced triplet gestation, suggest that cornstarch, which can be catabolized by debranching enzymes, may be used to maintain a constant state of maternal and fetal euglycemia and correct many metabolic abnormalities. Our data suggest that patients with glycogen storage disease type Ia can be safely managed in pregnancy under a tightly monitored and regulated protocol of raw cornstarch feedings. PMID- 2304724 TI - Successful pregnancy with isolated herpes simplex virus encephalitis: case report and review of the literature. AB - Isolated herpes simplex virus encephalitis in pregnancy is a rare illness with an elusive diagnosis. We describe the second patient to survive this disease and the first to have no sequelae, because of prompt diagnosis and treatment with acyclovir. PMID- 2304725 TI - Multiple myeloma in pregnancy: a case report. AB - Multiple myeloma, a generalized malignancy resulting from the proliferation of a single clone of neoplastic plasma cells, occurs rarely in pregnancy. This is the fifth documented case of pregnancy in a woman with this disorder. Clinical features of multiple myeloma include bone pain, pathologic fractures, neurologic deficits, and frequent bacterial infections. Laboratory evaluation often reveals hypercalcemia, anemia, and some degree of renal failure. Both radiation therapy and chemotherapy are used to treat multiple myeloma. Although the ultimate prognosis of a woman with this disease is poor, the offspring are apparently unaffected. PMID- 2304726 TI - Multiple myeloma in pregnancy: a case report. AB - We report here a 33-year-old patient found at 20 weeks' gestation to be anemic and to have both a serum M-protein (immunoglobulin [Ig]G kappa) and a kappa-type urinary Bence Jones protein. The concentration of these proteins, measured during pregnancy and in the postpartum period, demonstrated the presence of the maternal serum IgG kappa component in the amniotic fluid and its transmission to, and eventual disappearance from, the newborn. PMID- 2304727 TI - Successful pregnancy outcome following mid-gestational uterine rupture and repair using Gore-Tex soft tissue patch. AB - The first reported gestational use of the Gore-Tex soft tissue patch (expanded polytetrafluoroethylene) for uterine repair and support is presented in a pregnant woman whose partially dehisced, congenitally abnormal uterus was operated upon at 19 weeks' gestation. Use of the expanded polytetrafluoroethylene Gore-Tex soft tissue patch for assisted uterine integrity in combination with a program of uterine tocolysis and close maternal/fetal surveillance averted a pregnancy loss. PMID- 2304728 TI - Magnetic resonance imaging to diagnose a mullerian anomaly during pregnancy. AB - An adolescent woman presented with a paravaginal mass during pregnancy. Magnetic resonance imaging was useful in diagnosing a mullerian anomaly consisting of a double uterus and cervix and blind vaginal pouch. Magnetic resonance imaging can be an important modality in the diagnosis of gynecologic conditions in the obstetric patient. PMID- 2304729 TI - Postabortal hemorrhage due to placenta increta: a case report. AB - Placenta accreta is defined as a condition involving an abnormal adherence of the placenta to the myometrium. It is rare for placenta accreta to present before 20 weeks' gestation; only eight cases have been previously reported. This case report describes a first-trimester placenta accreta which presented during suction curettage for missed abortion. The major risk factors for placenta accreta are related to previous uterine trauma. Considering the rising rate of operative births in the United States, it is possible that the incidence of placenta accreta in early gestation will increase. PMID- 2304730 TI - Non-Hodgkin lymphoma of the puerperal uterus. AB - Non-Hodgkin lymphoma was diagnosed initially in a curettage specimen of a puerperal uterus 3 weeks after normal delivery of a healthy infant. The disease, which probably existed during the last trimester of pregnancy, was classified as clinical stage IVb. Combination chemotherapy resulted in immediate improvement and complete remission after several months. Histopathologic examination of the uterus 10 months after starting therapy demonstrated complete disappearance of the malignant lymphoma. PMID- 2304732 TI - Prolactinoma in wall of ovarian dermoid cyst with hyperprolactinemia. AB - A 41-year-old woman with long-standing amenorrhea and hyperprolactinemia that disappeared after hysterectomy and bilateral salpingo-oophorectomy was found to have a prolactinoma in the wall of a dermoid cyst. Prolactin was demonstrated in the tumor cells by immunohistochemical staining. PMID- 2304731 TI - Ovarian carcinoma arising in atypical endometriosis. AB - Malignant transformation is a rare but recognized complication of gonadal and extragonadal endometriosis. Morphologic documentation of the continuous transition from benign endometrioid epithelium through epithelial atypia to invasive carcinoma within the same organ is necessary to prove that the cancer arose from endometriosis. This stringent criterion, put forward by Scott, has rarely been fulfilled. We report a case with a chronologic association between ovarian endometriosis showing foci of atypia and a subsequent large clear-cell carcinoma arising in the same ovary 3 years later. We recommend close scrutiny of cellular atypia in endometriosis to define lesions that may be preneoplastic and require an extended surgical approach. PMID- 2304733 TI - The influence of endometriosis on the staging of cervical cancer. AB - Pelvic endometriosis often presents as nodularity of the uterosacral and broad ligaments. Therefore, the presence of unrecognized pelvic endometriosis in cervical cancer patients can masquerade as parametrial spread of tumor, preventing correct assessment of stage of disease. A review of three cases in which these disease processes coexisted demonstrates that endometriosis can easily be mistaken for tumor extension on pelvic examination, computed tomography, and even gross inspection at laparotomy, resulting in incorrect staging and inappropriate management decisions. Because clinical staging often is inaccurate in cervical cancer patients with a history of endometriosis, pre treatment operative assessment should be considered and frozen sections are recommended to assist with intraoperative management whenever the diagnosis of endometriosis could be entertained. PMID- 2304734 TI - Cis-platinum combination chemotherapy during pregnancy for advanced epithelial ovarian carcinoma. AB - Epithelial carcinoma of the ovary, a rare complication of pregnancy, was diagnosed at 16 weeks' gestation after presentation as an acute abdomen. Exploration with conservative surgery was done, and cis-platinum-based combination chemotherapy was administered for the remainder of the pregnancy. Induction and vaginal delivery resulted in a successful outcome for mother and fetus. Postpartum laparotomy was negative. PMID- 2304735 TI - Zollinger-Ellison syndrome due to a borderline mucinous cystadenoma of the ovary. AB - A Zollinger-Ellison syndrome due to an ovarian mucinous cystadenoma of borderline malignancy is reported in a 76-year-old woman. Immunostaining procedures showed reactivity for gastrin in neoplastic cells. After operation, the patient has remained without symptoms for 6 years. This is the fifth case reported in the literature. All of these ovarian tumors were considered mucinous cystadenomas histologically. PMID- 2304737 TI - Nurses help lead interprofessional team. PMID- 2304736 TI - Prazosin-induced stress incontinence. AB - A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy. PMID- 2304738 TI - Skin graft vestibuloplasty exostosis. A report of two cases. AB - Two cases of exostosis developing after mandibular vestibuloplasty and floor-to mouth lowering with split thickness skin graft are presented, one with multiple recurrences. The lesion is clinically and microscopically described. Hypotheses with respect to the development of this phenomenon are proposed. PMID- 2304739 TI - Analgesic and antiinflammatory effects of glucamethacin (a nonsteroidal antiinflammatory analgesic) after the removal of impacted third molars. AB - A double-blind study was undertaken to compare the effects of glucamethacin, aspirin, and placebo in the control of pain, trismus, and postoperative swelling of 59 outpatients who underwent the surgical removal of impacted lower third molars. Aspirin (1000 mg three times a day) was superior to placebo in one of the analgesic parameters studied, whereas glucamethacin (140 mg three times a day) was not superior to placebo. Both drugs significantly reduced the occurrence of trismus on the day after surgery, but no differences with placebo were found 48 hours postoperatively. In the study of postoperative swelling, no significant differences were found between the medications and the placebo in the postoperative period. It is concluded that glucamethacin, a nonsteroidal antiinflammatory drug, produces a minimal analgesic effect and does not relieve postoperative swelling in the dental patient undergoing surgical removal of impacted third molars. PMID- 2304740 TI - Finger injury resulting from pulse oximeter probe during orthognathic surgery. AB - Pulse oximetry is a useful technique for perioperative monitoring of the surgical patient. The use of the finger clamp design of oximeter probes may cause finger injury in lengthy surgical procedures. A case is presented and discussed with respect to an ischemic finger injury created by an oximeter probe during a hypotensive anesthetic technique. Avoidance of this type of problem includes proper placement of the probe on the finger and changing the probe to a different finger every 3 to 4 hours. PMID- 2304741 TI - Persistent buccopharyngeal membrane with cleft palate. A case report. AB - A case of persistent buccopharyngeal membrane associated with cleft palate is reported. Persistence of the buccopharyngeal membrane results in partial fusion of the jaws and inability in opening and should be labeled as partial syngnathia. An association of this condition with cleft palate occurs as a part of the aglossia-adactylia and the popliteal pterygium syndromes. Though infrequently reported in the literature, presence of a persistent buccopharyngeal membrane associated with only cleft palate, without the other characteristics of the syndromes, does occur and should be recognized as a separate developmental defect. PMID- 2304742 TI - A three-year follow-up of patients with reciprocal temporomandibular joint clicking. PMID- 2304743 TI - Prevalence of oral lesions among HIV-infected intravenous drug abusers and other risk groups. AB - To study the prevalence of oral manifestations, we examined 217 patients infected with the human immunodeficiency virus (HIV). Most of our patients were intravenous drug abusers (IVDAs) (65%). Other risk categories were represented by IVDAs who were also male homosexuals or bisexuals (11%), male homosexuals and bisexuals (16%), sexual partners of HIV-infected patients (5%), and hemophilic persons and recipients of blood transfusions (3%). Forty-six patients were women and 171 were men, with a median age of 27 years (range, 11 to 65 years). At the time of first examination, 38% of patients had asymptomatic HIV infection, 36% had lymphadenopathy syndrome, 17% had AIDS-related complex, and 9% had AIDS. Oral manifestations were observed in 89 (41%) patients. Of these, 15 had asymptomatic infection, 23 had lymphadenopathy syndrome, 27 had AIDS-related complex, and 24 had AIDS. Increasing severity of disease was significantly associated with higher prevalence of oral lesions (p less than or equal to 0.0001). Candidiasis was the most common oral lesion, followed by hairy leukoplakia. Kaposi's sarcoma, melanotic macules, herpes labialis, condyloma acuminatum, perioral molluscum contagiosum, and bacterial glossitis due to Escherichia coli infection were found in a small number of patients. Results of culture for fungi, available for 203 patients, revealed that 51% of patients with positive Candida cultures had clinical evidence of candidiasis. Our study demonstrates that oral lesions are also important signs of HIV infection among IVDAs. Early diagnosis of these manifestations is becoming increasingly significant in the practice of dentistry. PMID- 2304745 TI - Progressive bulbar palsy: a case report of a type of motor neuron disease presenting with oral symptoms. AB - A case is presented of a patient with progressive bulbar palsy, a form of motor neuron disease, which is a progressive degenerative disorder of the motor nuclei in the medulla producing atrophy and fasciculations of the musculature of the tongue, dysarthria, dysphagia, and excessive accumulation of secretions. The patient may initially seek dental consultation. Clinicians should be aware of the signs and symptoms of this inexorably fatal disease so that an early neurologic referral is made and the appropriate symptomatic therapies instituted. PMID- 2304746 TI - Bimaxillary hyperplasia: the facial expression of homozygous beta-thalassemia. AB - A boy born in Curacoa, who was 6 years old at his initial visit and known to have homozygous beta-thalassemia, is described. Emphasis is directed to the typical facial expression. The possibility of surgical treatment of the maxillary hypertrophy is discussed. However, in view of the limited life expectancy of these patients, correction should not be performed before adolescence. PMID- 2304744 TI - Oral complications in type 1B glycogen storage disease. AB - A case of type 1b glycogen storage disease (GSD) in which neutropenia and neutrophil dysfunction were prominent features is described. Oral complications included rapidly progressive periodontal disease and recurrent mucosal ulceration. PMID- 2304747 TI - Lichen planus with simultaneous involvement of the oral cavity and genitalia. AB - Five women with reticular and/or erosive lichen planus of the oral cavity associated with mucous involvement of the genitalia are reported. The presence of a typical lesion in one of these sites requires search for other common sites of involvement as well as manifestations of systemic diseases. Early management and careful follow-up of patients with chronic erosive and atrophic lesions of the vulva should be instituted to prevent dyspareunia. The use of the term plurimucosal lichen planus instead of vulvo-vagino-gingival syndrome is proposed. PMID- 2304748 TI - Intraoral manifestation of thromboangiitis obliterans (Buerger's disease). AB - A case of thromboangiitis obliterans (Buerger's disease) showing vascular lesions in the oral cavity is presented. To our knowledge, this is the first report of involvement of branches of the external carotid artery with this disease. The clinical, radiographic, plethysmographic, and histologic features of Buerger's disease are presented. Etiologic factors, pathogenesis, and treatment modalities are discussed. PMID- 2304750 TI - Anatomy of the root apex and its histologic changes with age. AB - There were 87 vital and 24 nonvital teeth for a total of 111 specimens from 47 patients. The specimens were prepared to a thickness of 500 microns with a Buehler Isomet Bone Saw. Distances were measured and recorded with a Bioquant II Image Analysis System. The mean age of the patients was 48.9 years. The median age was 52 years. The range was 51 years, with a maximum of 77 years and a minimum of 26 years. There is a positive correlation, which could not have occurred by chance, that as age increases the deviation and the width of the foramen opening both increase. This increase appears to be a result of apical cemental thickening that occurs as the patient ages. The tissue in the apical area seems to be capable of generating additional cementum as the tooth ages. The cementodentinal junction width, or most apical extent of the dentin, remains constant. PMID- 2304749 TI - Healing of primate dental pulps capped with Teflon. AB - The pulps of Rhesus monkey teeth were exposed and capped with three materials: Teflon, a commercial hard-set calcium hydroxide (Ca(OH)2) material, and Ca(OH)2 plus saline. Experimental test periods were 3, 10, and 21 days, and 5 and 8 weeks. After treatment, the teeth were removed and processed for routine histologic evaluation. Teeth treated with the two Ca(OH)2 materials showed resolution of the inflammatory response and hard tissue formation at the exposure site as early as 10 days postoperatively, with consistent healing at 21 days and longer. Teflon had a similar soft tissue healing pattern but at a slower rate. Hard tissue formation at the exposure site in the teeth treated with Teflon was infrequent at the early time periods and present in only 20% of the teeth treated for 5 and 8 weeks. By evaluating the soft and hard tissue responses of the Ca(OH)2-capped and Teflon-capped teeth it may be possible, in future studies, to identify events unique to odontoblast differentiation during pulpal healing. PMID- 2304751 TI - Axial temporomandibular joint morphology: a correlative study of radiographic and gross anatomic findings. AB - In degenerative diseases of the temporomandibular joint the mandibular condyle demonstrates changes in contour, including flattening and enlargement, resulting in an increased diameter of the articular surface. The purpose of this study was to determine if such alterations in the shape of the mandibular condyle can be visualized in submentovertex (axial) radiographs and correlated with pathologic changes of the temporomandibular joint. Submentovertex radiographs of 18 human cadaver specimens were made. The radiographic condylar dimensions, morphologic condylar outline, and angle of the condylar axis with respect to the transmeatal line were determined. The specimens were dissected and disarticulated, and radiographic findings were compared to anatomic structure. Osseous abnormalities were found in 21 of the 36 joints studied (58%). Perforations of the disk were found in nine of 31 joints (29%) investigated. No statistically significant differences between the normal condyles and condyles displaying osseous abnormalities were found in any of the radiographic parameters studied. PMID- 2304752 TI - Reversed layer position in rotational panoramic radiography. AB - In rotational panoramic radiography, the image layer is generally positioned between the rotation center of the beam and the film. It is also possible to create a layer that is positioned between the rotation center and the x-ray source. The reversed layer position is useful clinically and gives rise to image properties that are somewhat different from the conventional geometry. PMID- 2304753 TI - Traumatically implanted glass bead. PMID- 2304754 TI - Shrapnel foreign body. PMID- 2304755 TI - Endolymphatic sac morphology following long-term kanamycin intoxication. AB - The well-known toxicity pattern of aminoglycoside antibiotics has been used with the aim to produce waste products in the inner ear. The endolymphatic sac was studied after daily intraperitoneal injection of 75 mg/kg kanamycin for 10 and 20 days to see whether or not the endolymphatic sac showed signs of increased phagocytic activity. The epithelium of the endolymphatic sac was reduced in height, the cells were swollen and extremely thin. The dark epithelial cells were outnumbering the light cells. The subepithelial tissue showed an edematous swelling containing few blood vessels, collagen fibrils and fibroblasts with an empty appearance. There were few wide lateral intercellular spaces and there were intraluminal free floating cells. There were, in all, no clear morphological signs of increased phagocytic activity in the epithelium of the endolymphatic sac. PMID- 2304756 TI - Clinical significance of positive summating potential in Meniere's disease. AB - The positive summating potential (+SP) in Meniere's disease was compared with that in normal ears and in cochlear deafness of other origin than endolymphatic hydrops in order to assess a specificity of the +SP in Meniere's disease. The +SP was recorded in 21 of 47 Meniere ears (45%) on stimulation with 8-kHz tone bursts, whereas the +SP was recorded in none of 10 normal-hearing ears and in 1 of 28 ears with cochlear deafness of other origin than endolymphatic hydrops (4%). The incidence of the +SP in Meniere's disease was higher on stimulation with 8-kHz tone bursts than with 4-, 2- and 1-kHz tone bursts and clicks. No correlation between SP amplitudes recorded with 2- and 8-kHz tone bursts was found. The results suggest that Meniere's disease may involve a pathophysiological condition which allows the +SP to be frequently recorded. PMID- 2304757 TI - Pre- and postoperative high-frequency audiometry in otosclerosis. A study of 53 cases. AB - A study was carried out to evaluate the results of stapes surgery in 53 cases of otosclerosis. The hearing function was measured pre- and postoperatively by means of conventional and high-frequency audiometry (Demlar 20K). The operative findings of the gradation of otosclerosis were compared with the pre- and postoperative audiometrical measurements. The results of this study point out that a clear relation exists between the preoperative high-tone audiogram and the gradation of otosclerosis. Stapedotomy does not influence the high-frequency threshold postoperatively. In conclusion, high-frequency audiometry can predict the state of stapes fixation in otosclerosis and this can be important in stapes surgery. PMID- 2304758 TI - Disorders of gaze during head rotation. AB - We investigated gaze functions during sinusoidal head rotation in patients with peripheral and central vestibular lesions. Various kinds of gaze disturbance appeared in relation to deficient compensation (labyrinthine lesions), inaccurate gain regulation (cerebellar lesions), impaired gaze-induced suppression (cerebellar lesions), and inadequate visual correction (brain stem lesions). Analysis of gaze during head rotation may help to understand the regulation system of the vestibulo-ocular reflex as well as to detect gaze disturbances in patients with vestibular disorders, which cannot be attained by conventional vestibular examinations. PMID- 2304759 TI - Prediction of sequelae following facial nerve palsy. AB - The severity of facial muscle synkinesis, contracture, spasm, crocodile tears and hearing impairment and/or tinnitus were observed carefully following facial nerve palsy and evaluated quantitatively by a scoring system. Using this system, a mathematical formula was obtained to predict sequelae from the severity of facial nerve palsy. The severity of palsy at 2 weeks and 2 months after its onset was an important sign for prediction of sequelae. PMID- 2304760 TI - Clinical symptoms of sleep apnea syndrome and automobile accidents. AB - Patients with clinical features of sleep apnea syndrome (SAS) and self-reported sleep spells at the wheel do poorly in simulated monotonous driving. To evaluate whether drivers with defined symptoms of SAS (heavy snoring, sleep disturbances and daytime sleepiness) compensate in real traffic by careful driving or not, the rate of car accidents over a 5-year period was investigated. A questionnaire was addressed to 140 patients with and 142 controls without symptoms associated to SAS. Seventy-three of the patients had a complete triad of SAS-associated symptoms. Fifty-two percent of these patients reported habitual sleep spells at the wheel, as opposed to less than one percent by the controls. The ratio of drivers being involved in one or more combined-car accident was similar for patients and control drivers, but for single-car accidents the ratio was about 7 times higher for patients with a complete triad of symptoms of SAS compared to controls (p less than 0.001). When corrected for mileage driven, the total number of single-car accidents was almost 12 times higher among patients with sleep spells whilst driving, compared to controls (p less than 0.001). It is concluded that drivers with the clinical features of SAS are at increased risk especially for single-car accidents and that the risk seems to vary with the severity of symptoms. PMID- 2304761 TI - Poorly-differentiated laryngeal malignancies. PMID- 2304762 TI - The Oregon Power of Attorney for Health Care: practical implications for nurses. PMID- 2304763 TI - Hot topics in research. PMID- 2304764 TI - [Requirements for successful pancreatic enzyme replacement therapy (comparative study of Kreon and Panpur)]. AB - Factors influencing the effectivity of replacement therapy with Panpur and Creon were controlled by in vivo and in vitro investigations. Both enteric coated preparations were equally acid protected, they even seemed to be more effective in hyperacid than in anacid chronic pancreatitis patients. Thus the uneven results of Panpur treatment in pancreatic steatorrhea cannot be explained by acid inactivation of the enzymes. Creon dose-dependently ameliorated the steatorrhea as well as vitamin B12 absorption while crushed but not the intact Panpur has only some insignificant effect. Good mixing of pancreatin with the B12-intrinsic factor - R protein complex and with the protein containing meal seems to be important for digestion of protein as well as fat. Unbound, overflowing trypsin activity of Panpur resulted in fast proteolytic inactivation of lipase. This could be diminished by soybean trypsin inhibitor which increased the in vivo effectiveness of the preparate. In summary Creon fulfilled two important factors of replacement therapy more successfully than Panpur: good mixing with meals and stability of lipase against proteolytic splitting, that is why it proved to be more effective for replacement therapy of pancreatic insufficiency. PMID- 2304765 TI - [Benign cystic mesothelioma of the peritoneum]. AB - A case of benign cystic peritoneal mesothelioma is reported. A 25-year-old woman presented a 8-year history of recurrent tumor and five operations because of the same. On the basis of this case and of 18 cases proved by electron microscopy reported by others the clinicopathological features and the problems of differential diagnosis are discussed. The ultrastructural examination is essential for the diagnosis of cystic mesothelioma. PMID- 2304766 TI - [The normal right-side electrocardiogram]. AB - QRS complex, ST segment and T wave were investigated in V1R--V8R right chest wall leads in 122 healthy individuals (76 women, 46 men, mean age: 36.8 years). There was no Q wave in V1-3R. Going towards V8R, occurrence of QR and QS complexes increased. R/S ratio was the highest in V8R, while second r wave (r') was found to be most frequent (in 20.5%) in V6R. ST elevation at 80 msec after J point was found in all right chest wall leads, most frequently (in 91%) in V2R. All three forms of T wave morphology (positive, negative, isoelectric) were observed in these leads. PMID- 2304768 TI - [Reflections on the parting words of the departing Editor in Chief]. PMID- 2304767 TI - [Hyperprostaglandin E syndrome in a nine-year-old child]. AB - The authors describe the history of a nine year old girl, with a disease that seemed to be hyperprostaglandin-E syndrome. They give a survey of the literature about the pathophysiological cause of the disease, the clinical and laboratory findings and the effect of indomethacin, which can inhibit the synthesis of prostaglandins. Prolonged treatment with indomethacin can decrease the urinary excretion of prostaglandine, polyuria and hypercalciuria and it can moderate the growth retardation. They found the same but milder clinical and laboratory features at the four year old brother of the patient too. PMID- 2304769 TI - Generic drugs: potential public health threat. PMID- 2304770 TI - Standards of medical care for patients with diabetes mellitus. American Diabetes Association. PMID- 2304772 TI - The state of the union: the AMA works. PMID- 2304771 TI - Comparing care of Pennsylvania patients with diabetes to national standards. PMID- 2304773 TI - Standards educate physicians about diabetes. PMID- 2304775 TI - Elderly sexuality examined. PMID- 2304774 TI - Fifty hours for the poor! PMID- 2304776 TI - Cyclosporine A for the treatment of new-onset insulin-dependent diabetes mellitus. AB - It is not known whether early immunosuppressive treatment can preserve long-term endogenous insulin secretion in subjects with insulin-dependent diabetes mellitus. In the present study, clinical remissions during the first year and C peptide production for 3 years were followed after 43 subjects with newly diagnosed insulin-dependent diabetes mellitus were randomly assigned to a cyclosporine A treatment group for 4 months or to a control group. Of the six cyclosporine A-treated subjects who had remissions, five were 19 years of age or younger, compared with two of the four in the control group. C-peptide production was present in 98% of all subjects after 4 months, in 88% after 1 year, and in 43% after 3 years. There were no significant differences in numbers of subjects with C-peptide production or in mean hemoglobin A1 levels, between cyclosporine A treated and control subjects after 3 years. Cyclosporine A treatment of subjects with newly diagnosed insulin-dependent diabetes mellitus for a period of 4 months does not have the ability to preserve residual beta-cell function. PMID- 2304777 TI - Psychosocial characteristics of homeless children and children with homes. AB - A comparison was made of 86 children from 49 homeless Boston families headed by women and 134 children from 81 housed Boston families headed by women. In both groups, the mothers were poor, currently single, and had been receiving welfare payments for long periods. Data were collected from the mothers by personal interview; standardized tests were administered to mothers and children (Denver Developmental Screening Test, Simmons Behavior Checklist, Children's Depression Inventory, Children's Manifest Anxiety Scale, and Child Behavior Checklist. The data indicate that many homeless children and poor children with homes have severe and pressing problems. Among preschool children, a higher proportion of homeless children than poor children with homes had one or more developmental delays (P less than .05), although their scores on the Simmons Behavior Checklist were similar. Among school-aged children, the scores of the homeless children were worse than those of the children with homes on the Children's Depression Inventory, Children's Manifest Anxiety Scale, and the Child Behavior Checklist, but only the difference on the Anxiety Scale approached statistical significance (P = .06). Both homeless children and poor children with homes generally had worse scores than most other comparison groups of children. Unless action is taken to improve the lot of all these children, it is likely that many will continue to have significant problems that will seriously hamper their ability to function. PMID- 2304778 TI - Screening for anxiety and depression in an adolescent clinic. AB - The Spielberger State-Trait Anxiety Inventory (STAI) and the Children's Depression Inventory (CDI) were administered to 228 consecutive adolescent clinic patients and provisional physician diagnoses were compared with test scores obtained in 205 valid replies. The age range was 10 to 17 with a mean +/- SD of 14.3 +/- 1.8 years. Racial distribution was 176 white, 21 black, 4 Asian, and 4 other. The provisional diagnoses were categorized as follows: medical diagnosis only, 140; psychiatric diagnosis only, 45; and combined medical/psychiatric diagnosis, 20. Mean scores +/- SD for the entire study population were STAI-State 41.1 +/- 10.9, STAI-Trait 41.3 +/- 11.8, and CDI 10.1 +/- 8.3. Odds ratios showed that patients with only a psychiatric diagnosis had higher STAI scores than those with only a medical diagnosis and those with a combined medical/psychiatric diagnosis; patients with only a psychiatric diagnosis and those with a combined medical/psychiatric diagnosis had higher CDI scores than those with only a medical diagnosis. The medical records of 30 patients in the medical diagnosis category with high STAI and CDI scores were reviewed; of 140 patients with medical diagnoses, screening detected 15 patients (10.7%) who warranted further intervention for psychiatric disorders. PMID- 2304779 TI - Chronic conditions, socioeconomic risks, and behavioral problems in children and adolescents. AB - Children with a chronic health condition have long been considered at excess risk for psychosocial morbidity. Despite an increasing prevalence of chronic childhood conditions and heightened concerns for the quality of life of the chronically ill, population-based studies of behavior problems among children with chronic physical conditions are rare. Findings on the epidemiology of behavior problems in a nationally representative sample of 11,699 children and adolescents aged 4 to 17 years in the United States are reported. Data included a 32-item parent reported behavior problem index, measures of chronic childhood conditions, measures of school placement and performance, and sociodemographic variables. Analyses confirmed that chronic physical conditions were a significant risk factor for behavior problems, independent of sociodemographic variables. Among children these differences were observed across all subscales; among adolescents the largest differences were found for the Depression/Anxiety and Peer Conflict/Social Withdrawal subscales. Rates of extreme behavior problem scores (those in the top 10th percentile) were 1.55 times higher among children with a chronic health condition compared with children without a chronic condition (95% confidence interval 1.29 to 1.86). These independent odds were lowered to 1.44 when covariates for confounding were introduced via a multivariate logistic regression. Other independent risks included the absence of either biologic parent (odds ratio 2.05), male gender (1.53), low vs high family income (1.30), low vs high maternal education (1.51), and young vs old maternal age at childbirth (2.57). Chronic health conditions were also a major risk factor for placement in special education classes and having to repeat grades. Despite evidence for effective interventions, health services for children with chronic conditions--particularly mental health services--remain fragmented, signaling the need for increased attention to behavioral problems and their treatment among all health professionals caring for children. PMID- 2304780 TI - Weight and menstrual function in patients with eating disorders and cystic fibrosis. AB - Many patients with eating disorders have menstrual dysfunction. In patients with anorexia nervosa, amenorrhea has been linked to weight loss. However, many patients with bulimia nervosa, even those of average or greater than average weight, also experience menstrual abnormalities, including amenorrhea. It was hypothesized that low weight per se is not responsible for menstrual dysfunction in patients with eating disorders. First, 16 patients with bulimia nervosa of average weight and 29 patients with cystic fibrosis of below average weight of similar menstrual age were compared. Of the patients with bulimia nervosa, 11 (73%) had had secondary amenorrhea at some time compared with 8 (28%) of the patients with cystic fibrosis (P less than .01). At the time of study, 6 (40%) of the patients with bulimia nervosa and 21 (78%) of the patients with cystic fibrosis were having regular cycles (P less than .01). Next 18 patients with anorexia nervosa were compared with 18 patients with cystic fibrosis matched for weight and menstrual age. Although 18 (100%) of the patients with anorexia nervosa had had secondary amenorrhea, only 6 (33%) of the patients with cystic fibrosis had amenorrhea. Although only 1 (6%) of the anorexia nervosa group was currently having regular cycles, 14 (78%) of the patients with cystic fibrosis were (P less than .0001). Closer approximation to ideal body weight was associated with regular menses only in the cystic fibrosis group. Exercise did not appear related to regularity of menstruation in any group. Body weight is not the major factor responsible for menstrual abnormalities in patients with eating disorders. PMID- 2304781 TI - Persistence of antibody and booster responses to reimmunization with Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children initially immunized at 15 to 24 months of age. AB - To evaluate the persistence of antibody after Haemophilus influenzae type b polysaccharide vaccine (PRP) and H influenzae type b polysaccharide diphtheria toxoid conjugate vaccine (PRP-D), a group of 141 infants initially immunized between 15 and 24 months of age were studied 1 year later. One month after immunization with PRP, the man anti-PRP antibody level was 0.27 microgram/mL and 1 year later was 0.29 microgram/mL (not significant). In the group immunized with PRP-D, the levels were 1.34 micrograms/mL and 1.20 micrograms/mL (not significant), respectively. To evaluate immunogenicity and safety of a booster immunization 1 year after initial vaccination, subjects were randomly assigned to receive saline, PRP, or PRP-D. In addition, 73 age-matched previously unimmunized subjects were vaccinated with PRP or PRP-D. In all groups, adverse reactions were minor and resolved by 48 hours. Subjects receiving booster immunization with PRP or PRP-D had significantly greater antibody responses than children of the same age receiving their first dose of vaccine. The highest antibody levels were achieved in children initially immunized with PRP-D, regardless of whether the booster vaccine was PRP (112.8 micrograms/mL) or PRP-D (122.0 micrograms/mL) (not significant). Antibody levels after booster vaccine were significantly lower in those initially given PRP compared with those initially given PRP-D but significantly higher than in age-matched previously unimmunized control subjects (PRP booster 3.16 micrograms/mL vs control of 0.62 microgram/mL [P less than .05]; PRP-D booster 12.31 micrograms/mL vs control 2.31 micrograms/mL [P less than .01]). PMID- 2304782 TI - Longitudinal study of adverse reactions following diphtheria-tetanus-pertussis vaccine in infancy. AB - A prospective study of immunogenicity and adverse effects of 1553 doses of diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) was performed in 538 children observed longitudinally from 2 months to 20 months of age. Subjects were randomized to the standard four-dose immunization schedule or to a three-dose schedule (with a saline injection substituted for DTP at 6 months of age). The three-dose schedule could not be recommended on the basis of serologic data. Compliance for completing a clinical observation form in the 48 hours following injections was greater than 99%. Fever, local reactions, or adverse behavioral effects were described in association with 96% of DTP doses and 36% of placebo injections. Contraindications to DTP immunization developed in 3% of study children. No convulsion, hypotonic hyporesponsive episode, encephalopathy, or temperature greater than 40.5 degrees C occurred. Behavioral and local inflammatory effects occurred maximally in the first 6 hours following vaccine but fever peaked later. There was no interrelationship between occurrence of local reaction and fever. Data suggest that age has more effect on the type and rate of adverse clinical events than does vaccine dose number. Existing antibody levels to vaccine components, lot of vaccine, breast-feeding, or gestational age did not affect rate or type of clinical reactions. Neither occurrence of reactions nor the use of acetaminophen affected antibody response to vaccine. PMID- 2304783 TI - Behavioral risks for human immunodeficiency virus infection in adolescent medical patients. AB - This paper is an examination of the extent to which adolescents in primary care indicated behavioral risk for human immunodeficiency virus infection, and the degree to which their clinic records reflected either awareness of such conditions or interventions for them. Levels of risk were assigned to the youths based on known risk factors in adult populations and arbitrarily selected natural breaks in the frequency of sexual behaviors. Of the sample, 3% were at high risk for human immunodeficiency virus infection because the adolescents engaged in prostitution, injectable drug use, male homosexual behavior, or had a sexually transmitted disease associated with genital ulcers or sores; 16% were at moderate risk because the youths had more than six sexual partners in the year preceding the interview or had nonulcerative forms of sexually transmitted disease; and the remainder were at low risk. Fewer than half of the youths at risk for human immunodeficiency virus infection sought or received help for any of their problem behaviors, while virtually all sought and received help for sexually transmitted diseases. Because a high proportion of the youths engaging in risky behaviors had sexually transmitted diseases, the most promising approach for prevention of human immunodeficiency disease infection is through health clinics that treat sexually transmitted diseases. These clinics could screen the youths for associated behavioral risk factors, and then offer preventive or interventive services. PMID- 2304784 TI - Mitral valve prolapse: associations with symptoms and anxiety. AB - Mitral valve prolapse has been studied extensively in the adult population, but less is known about it in children. Therefore, 813 children between 9 and 14 years of age were examined by a team of cardiologists and technicians. The children also responded to a questionnaire concerning the presence of symptoms and the What I Think and Feel anxiety instrument. The prevalence of mitral valve prolapse using auscultatory criteria was 4.2% (6.2% for girls, 2.3% for boys). Of those with mitral valve prolapse, 85% had a solitary click, 9% had a click and systolic murmur, and 6% had multiple clicks. Children with auscultatory mitral valve prolapse were less likely to have symptoms than those free of cardiac abnormalities. No difference in average anxiety scores was detected between the two groups. It is concluded that auscultatory mitral valve prolapse is common in children and not accompanied by an increased likelihood of symptoms or anxiety. PMID- 2304785 TI - Natural killer cell immunodeficiency in siblings: defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokine-activated killer cytotoxicities. AB - A immunodeficiency of natural killer cells as effectors for natural killer and lymphokine-activated killer cytotoxicities was first demonstrated in siblings. Two of three male siblings persistently lacked natural killer activity against K562 target cells as assayed by a 51Cr-release assay: percent lysis values were less than 1.0% as compared to the normal lymphocyte values of 43.5% +/- 6.2% (mean +/- SD). Their lymphocytes did not develop natural killer cell activity by changing effector to target ratios, prolonging the incubation time, or stimulating them with interferon-alpha or interleukin 2. Numbers of lymphocytes bearing Leu-7, CD16, or NKH-1 were normal but those of Leu-7-, CD16+ cells were decreased as estimated by flow cytometry. Single cell-in-agarose assays showed normal numbers of natural killer cells capable of binding to a target cell but incapable of killing it. They had depressed levels of lymphokine-activated killer activity, which was totally eliminated by the treatment with OKT3 and complement. This result indicates that the patients' natural killer cells are also defective in the capacity to work as effectors for lymphokine-activated killer activity. The patients' natural killer cells did not produce natural killer cytotoxic factor activity. Antibody-dependent cellular cytotoxicity and cytotoxic T lymphocyte cytotoxicity were normal. These results demonstrate a selective natural killer cell deficiency as effectors for natural killer and lymphokine activated killer cytotoxicities with a familial tendency, in which there is defective killing with the absence of natural killer cytotoxic factor activity. PMID- 2304786 TI - Safety and immunologic response to Haemophilus influenzae type b oligosaccharide CRM197 conjugate vaccine in 1- to 6-month-old infants. AB - A Haemophilus influenzae type b oligosaccharide-CRM197 conjugate (HbOC) vaccine was evaluated for safety and immunogenicity in 432 infants 1 to 6 months of age. In a multicenter study involving 10 sites in six states, infants were vaccinated with three 10-micrograms doses of HbOC at 2-month intervals. Side effects associated with vaccination were mild, transient, and occurred in fewer than 2% of the subjects. More than 90% of infants of all ages responded after two doses, and more than 98% had anti-H influenzae type b capsular polysaccharide (HbPs) antibody levels greater than or equal to 1 microgram/mL after three doses. One month after the third vaccination, the geometric mean anti-HbPs antibody levels were 16.84, 26.23, and 29.11 in infants initially vaccinated at 1 to 2, 3 to 4, and 5 to 6 months of age, respectively. A long-term antibody response was observed; more than 80% of these infants had anti-HbPs levels greater than or equal to 1 microgram/mL at 2 years of age. The HbOC generated an immune response characteristic of a protein antigen; IgG anti-HbPs antibodies of IgG1 subclass predominated and the response could be boosted. The immune sera killed H influenzae type b when evaluated in an in vitro bactericidal assay. The data indicate that HbOC safely primed and boosted the immune system of young infants, providing long-lasting protective levels of anti-HbPs antibodies. PMID- 2304787 TI - Immunization of children with acute lymphoblastic leukemia with live attenuated varicella vaccine without complete suspension of chemotherapy. AB - A total of 44 children with acute lymphoblastic leukemia were immunized against chickenpox with the Oka/Merck strain live attenuated varicella vaccine. Of these children, 24 continued oral chemotherapy with 6-mercaptopurine during the immunization period and 20 had suspension of all chemotherapy for 1 week before and 1 week after the vaccine. Seroconversion, as determined by the detection of fluorescent antibody to membrane antigens, occurred in 91% and did not differ between patients continuing 6-mercaptopurine from those in whom chemotherapy was suspended. Fever and/or rash occurred in less than one third of vaccinated children. Unexpected reactions occurred in two vaccinated children, one from each group, both of whom had low absolute lymphocyte counts (less than 750/microL) on the day of immunization. Vaccine-induced immunity appeared effective in preventing or modifying chickenpox after exposure to natural disease. PMID- 2304789 TI - Acute mental status changes in children with systemic cancer. AB - Acute changes in mental status (AMS) develop in children with cancer from a multitude of cancer- and treatment-related complications. To determine the incidence, etiology, and outcome of children with cancer who had AMS, the medical records of all children under 18 years of age with systemic cancer (excluding primary central nervous system tumors) who had AMS in our institution during the years 1981 through 1987 were reviewed. AMS developed in 89 of 815 children at risk (11%). The AMS was caused by seizures in 53 (60%), an encephalopathy in 24 (27%), and a stroke syndrome in 12 (13%). AMS occurred in 42 of 305 (14%) with leukemia, 16 of 139 (12%) with lymphoma, 14 of 136 (10%) with sarcoma, 10 of 104 (9%) with neuroblastoma, and 7 of 104 (5%) with other malignancies. Children with acute lymphocytic leukemia were more prone to having seizures (61%), while children with nonacute lymphocytic leukemia were almost equally likely to have encephalopathies, strokes, or seizures. Children with lymphoma were admitted for treatment most often with an encephalopathy (44%). Etiologies for AMS were evaluated vigorously, and one or more etiologies were identified in 80 of 89 (89%) patients. Dependent on the type of tumor, the anticancer treatment used and, timing during the course of illness AMS occurred, specific diagnoses were more likely. Neurologic morbidity and mortality were dependent on the cause of AMS. Children with seizures that were initially difficult to control were more likely to require long-term anticonvulsant therapy. PMID- 2304788 TI - Obesity in black adolescent girls: a controlled clinical trial of treatment by diet, behavior modification, and parental support. AB - Recent findings indicate that nearly 50% of black American women are obese and that adolescence is a critical period for the development of their obesity. This study investigated the efficacy of a behavioral weight control program in 36 black female adolescents with a mean age of 14.0 years, weight of 95.0 kg, and height of 163.2 cm. All subjects participated in the same 16-week program but had different levels of parent participation: (1) child alone with no parent participation; (2) mother and child treated in the same session; and (3) mother and child treated in separate but concurrent session. At the end of the 16-week program, children in the three conditions lost 1.6, 3.7, and 3.1 kg, respectively. Differences among conditions were not statistically significant; however, a secondary analysis revealed that the greater the number of sessions attended by mothers, the greater their daughters' weight losses. Weight reduction was associated with significant improvements in body composition, serum total cholesterol concentrations, and psychological status. Results are discussed in terms of the need to improve the maintenance of weight loss in adolescents and to explore possible differences between black and white females in their preferred body types. PMID- 2304790 TI - The pediatrician as a role model in the career choice of medical students. PMID- 2304791 TI - Munchausen syndrome by proxy: father as a perpetrator. AB - We conclude that fathers, as well as mothers and female caretakers, can be the perpetrators in Munchausen syndrome by proxy. Those same fathers may be even more difficult to detect when they do not fit previously described personalities and traits associated with mothers. We do not know if this case was an isolated incident or if some cases go undetected because fathers are not suspected as perpetrators. We hope that the case described in this article will alert the medical community to the possibility of either parent as a perpetrator in Munchausen syndrome by proxy. PMID- 2304792 TI - On hummingbirds, extracorporeal membrane oxygenation, and IBM. PMID- 2304793 TI - Could hypobilirubinemia be bad? PMID- 2304794 TI - Ghost blasting with button batteries. PMID- 2304795 TI - More concerning asthma and exercise. PMID- 2304796 TI - Acquired immunodeficiency syndrome and adolescence. PMID- 2304797 TI - Infants and children with acquired immunodeficiency syndrome: placement in adoption and foster care. PMID- 2304798 TI - Pseudoephedrine dangers. PMID- 2304799 TI - Selected papers presented at the fourth annual research symposium of the Society for Developmental Pediatrics. Williamsburg, VA, November 17 to 19, 1988. PMID- 2304800 TI - Tone and reflex development before term. AB - The evolution of tone and reflexes from 25 weeks postmenstrual age (gestational age plus chronologic age) to term in a population of 42 surviving infants is described. The infants were born in 1983 at the Johns Hopkins Hospital, had birth weights less than 1300 g, were examined weekly until neonatal intensive care unit discharge, and did not develop cerebral palsy. Lower-extremity flexor tone was first detectable at 29 weeks post-menstrual age by the popliteal angle and heel to ear maneuvers. Flexor tone, recoil, and hyperreflexia were all noted 2 to 3 weeks earlier in the lower extremities (33 to 35 weeks) than in the upper extremities (35 to 37 weeks). Hip tone (35 to 37 weeks) followed knee flexor tone, but preceded shoulder tone (37 to 38 weeks). Trunk tone on ventral suspension emerged closer to term (36 to 40 weeks), and more than half of infants evaluated at term continued to demonstrate head lag when pulled to sitting position. The emergence of the primitive and pathologic reflexes reflects (both in timing and pattern) the evolution of tone: development of the reflexes in the lower extremities precedes that of those in the upper extremities, and development of the distal reflexes precedes that of the proximal. Maturation of tone, deep tendon reflexes, pathologic reflexes, and primitive reflexes occurs in an orderly, sequential manner, with a well-defined pattern: caudocephalad (lower extremities to upper extremities) and centripetal (distal to proximal). PMID- 2304801 TI - Nonhandicapped very-low-birth-weight infants at one year of age: developmental profile. AB - The developmental profile of 61 very-low-birth-weight infants without major cognitive, motor, or sensory deficits was compared with that of 28 term infants at 1 year chronologic age. The groups significantly differed in two ways on the Revised Gesell Developmental Schedules. First, very-low-birth-weight infants were more likely than term infants to have significant discrepancies between either their fine motor or language abilities and their early problem-solving skills as measured by the Adaptive scale of the Gesell. Second, across all fields of behavior (adaptive, gross motor, fine motor, language, and personal/social), very low-birth-weight infants scored significantly below term infants. The very-low birth-weight infant's motor performance significantly correlated with bronchopulmonary dysplasia, intracranial hemorrhage, and number of days spent in the hospital. Language performance significantly correlated with intracranial hemorrhage, birth weight, and sex. These findings underscore the limitations of global developmental scores to describe adequately the developmental performance of very-low-birth-weight infants. Instead, a comprehensive assessment of all fields of behavior is necessary to provide an accurate profile of this high-risk group. PMID- 2304802 TI - Precursors of reading delay: neurodevelopmental milestones. AB - The relationship between current reading ability and the achievement of early language and motor developmental milestones was evaluated in 240 children, aged 7 1/2 years, whose language and motor achievement had been charted at each well baby visit during the first 2 years of life. Those children whose composite reading score was 6 months behind their chronologic age on the Woodcock-Johnson Psychoeducational Battery were classified as having reading delay. Relationships to reading outcome were assessed for individual infant milestones, for critical screening values, and by statistical techniques that characterized the developmental process rather than single milestones. Significant differences (P less than .05) were noted between children with and without reading delays for the following milestones: 4 to 6 words, 7 to 20 words, 50 words, 2-word sentences, and 5 and 8 body parts. The positive predictive value of slower milestone achievement ranged from 0% to 50%. Techniques that focused on the developmental process during the first 2 years (either rate of achievement of neurodevelopmental milestones or order of milestone acquisition) were better able to classify children with reading delay (sensitivity = .73, specificity = .78). Although the language milestone measures did not classify children sufficiently well to be diagnostic, the data served to determine whether a child would be at high risk based on performance rather than historical factors. PMID- 2304803 TI - Integration of soft signs in academically normal and academically at-risk children. AB - The development of motor and sensory proficiency and the integration of soft signs were analyzed for 38 children with average achievement and 29 children achieving below grade level. Motor coordination, speed, and inhibition, as well as the development of sensory function, were evaluated at the time of entrance to kindergarten and again during the first grade. The performance of both groups progressed on tasks measuring motor speed and coordination as well as tactile integration. Although the children achieving below grade level continued to perform the majority of tasks poorly in comparison with the children performing at grade level, on most of the measures they evidenced definite catch-up or greater gain than the children performing at grade level. Their progress on the motor speed and coordination tasks supports the hypothesis of a developmental lag in these areas. Results of tests of motor inhibition were notable for an absence of progression. That children achieving below grade level did not advance in this area would argue against the hypothesis of a developmental lag for all soft signs. Although results of this longitudinal study are preliminary, findings to date would allow for the possibility that both deficits and lags are responsible for the differences between the academically normal and academically at-risk children. PMID- 2304804 TI - Disorders of attention and activity level in a referral population. AB - Of 614 children referred for an evaluation of hyperactivity and inattention, the 422 (68.7%) who qualified for a diagnosis of attention deficit disorder (ADD) were compared with the 192 (31.3%) who did not. The children with ADD had significantly higher full-scale IQ scores, verbal scores, and parental educational levels. They also had a significantly higher incidence of specific learning disabilities (73.7%). The absence of hyperactivity in children with ADD further exaggerated the differences in learning disability between the two groups. Cognitive limitation, severe parental psychopathology, and child neglect/abuse were significantly higher in the group without ADD. The two groups did not differ in the incidence of parental or child depressive symptomatology, motor diagnoses, language disorders, conduct disorders, and psychosomatic complaints. That only 29 children in whom ADD was absent (4.7% of all referrals) had been given a trial of stimulant medication does not support the presence of a major abuse of such drugs in the community. PMID- 2304805 TI - Behavioral deficits in rats with minimal cortical hypoplasia induced by methylazoxymethanol acetate. AB - Methylazoxymethanol, a short-acting antimitotic agent, produces marked cortical hypoplasia in fetuses when injected into pregnant rats. These offspring also have increased cortical concentrations of biogenic amines associated with hyperactivity and learning deficits. In this experiment, rats with a relatively mild degree of methylazoxymethanol-induced cortical hypoplasia were studied to determine whether these neurochemical and behavioral abnormalities persisted. Sprague-Dawley pregnant rats were injected intraperitoneally on day 15 of gestation with methylazoxymethanol acetate (25 mg/kg). Total brain weight was reduced by 12% and cortical slab weight by 28% in methylazoxymethanol-exposed offspring. They were more active than control rats and showed a trend toward slower learning in a swim maze. Affected offspring had increased cortical concentrations of norepinephrine, 5-hydroxyindoleacetic acid, and glycine. There was no significant difference in the concentrations of serotonin gamma aminobutyric acid, aspartic acid, glutamic acid, or glutamine. Methylazoxymethanol-lesioned animals with mild cortical hypoplasia remained measurably hyperactive and may serve as a model for the study of neurotransmitter and neuropathologic abnormalities associated with hyperactivity in children with microcephaly. PMID- 2304806 TI - Children with self-injurious behavior. AB - Self-injurious behavior is a serious problem that is not uncommon among individuals with mental retardation. Medical and developmental characteristics of 97 children, adolescents, and young adults (age range 11 months to 21 years, 11 months) assessed and treated for self-injurious behavior in a specialized, interdisciplinary inpatient unit between 1980 and 1988 were reviewed. This population differed from those reported in previous studies in that it was of school age and predominantly community based. Severe or profound mental retardation was present in 82.5% of our patients. The causative diagnoses associated with self-injurious behavior were similar to those of severe mental retardation alone. Associated disabilities represented at greater than expected frequencies included pervasive developmental disorders, visual impairment, and a history of infantile spasms. Most patients (81.4%) engaged in more than one type of self-injurious behavior. The most common topographies were head banging, biting, head hitting, body hitting, and scratching. Physical injury was documented in 77% of cases; the injuries most frequently reported were excoriations, scars/callus formation, hematomas, and local infection. As community placement of handicapped individuals continues to increase, pediatricians will be called upon to monitor patients who engage in self injurious behavior. PMID- 2304807 TI - Otitis media in children with learning disabilities and in children with attention deficit disorder with hyperactivity. AB - A retrospective study was conducted to compare history of middle ear disease children with an attention deficit disorder with hyperactivity (ADD-H) and children with a learning disability. Of 138 children evaluated in a child development clinic, learning disability without ADD-H was diagnosed in 45 (29 boys, 16 girls; mean age = 9.5 years) and ADD-H without learning disability was diagnosed in 21 (17 boys, 4 girls; mean age = 8.5 years). Based on parental report, children with ADD-H had significantly more complaints of earaches during the preceding 3 months and significantly more ear infections during the preceding year. Specifically, no between-group differences were observed for total number of ear infections since birth, extended antibiotic therapy, tympanostomy tube placement, or recent hearing problems. Although middle ear disease in preschool children has repeatedly been linked to later language deficits, this study suggests that middle ear disease in school-age children may also be associated with hyperactivity and/or inattention, independently of learning disability. PMID- 2304808 TI - Detection and discrimination thresholds for auditory periodicity. AB - Complex periodic auditory signals, produced by the Guttman-Julesz procedure of repeating segments of random noise, were employed to address the low region of auditory periodicity. Periodicity detection and discrimination tasks were examined with a common experimental procedure and a common measure of thresholds. Typically, detection and discrimination performance suffer at extremely low periodicities, presumably because of the extremely close spacing of harmonics throughout the auditory spectrum. Interaural phase effects are extremely weak for these signals, being largely confined to threshold-detection tasks. Despite qualitative phenomenological differences for different periodicity regions, detection and discrimination functions show no sharp discontinuities over a wide range of periodicities. PMID- 2304809 TI - Focused attention in three-dimensional space. AB - The size of focused attention was assessed within a three-dimensional display. Subjects viewed random-dot stereogram displays in which they responded differentially to vertical and horizontal bars. Adjacent noise elements either were identical to the response target or specified the opposite response. The position of the noise elements was varied in depth according to binocular disparity. Interference by incompatible noise elements decreased with depth separation between the noise elements and response target. In addition, interference was greater for noise elements that were more distant from the observer than from the response target than it was for noise elements that were closer to the observer than to the response target. The implications of these results for a viewer-centered representation of focused attention in depth are discussed. PMID- 2304810 TI - Auditory streaming and the continuity illusion. AB - In the present experiment, auditory stream organization was investigated in the presence of perceptually restored continuity. It was found that auditory streaming processes tend to yield the same perceptual organization independently of the presence or absence of perceptual restoration. Other observations include the dominance of frequency proximity over trajectory as a perceptual organization principle, and the effect of harmonic enrichment on perceptual grouping. PMID- 2304811 TI - Confidence intervals for the parameters of psychometric functions. AB - A Monte Carlo method for computing the bias and standard deviation of estimates of the parameters of a psychometric function such as the Weibull/Quick is described. The method, based on Efron's parametric bootstrap, can also be used to estimate confidence intervals for these parameters. The method's ability to predict bias, standard deviation, and confidence intervals is evaluated in two ways. First, its predictions are compared to the outcomes of Monte Carlo simulations of psychophysical experiments. Second, its predicted confidence intervals were compared with the actual variability of human observers in a psychophysical task. Computer programs implementing the method are available from the author. PMID- 2304812 TI - Priming effects in perceptual classification. AB - Priming stimuli that spatially flank a fixated target stimulus may cause either facilitation or interference with target classification, depending on experimental context. Two experiments demonstrated distinct effects of response compatibility and semantic congruity between flankers and target. Response competition occurred when targets were flanked by context stimuli associated with the opposite response, but this effect diminished when the target was delayed relative to the flankers. Facilitative priming by response-compatible flankers, in contrast, required prior exposure of the flankers, and was strongly influenced by the semantic congruity of flankers and targets. These differing time courses suggest that perceptual priming encompasses a variety of distinct underlying cognitive and motor events. PMID- 2304813 TI - Angular velocity discrimination. AB - Three experiments were designed to investigate naive observers' abilities at discriminating the rotational velocities of two simultaneously viewed objects. In Experiment 1, rotations could occur about parallel or orthogonal axes, with initial orientations in phase or out of phase, and (for parallel rotational axes) in the same or opposite direction. Differential thresholds were approximately 10%. In Experiment 2, stimulus objects differed in the number of faces revealed in rotation (three vs. four). Observers' response curves had no greater spread, but their PSEs (points of subjective equality) were shifted such that there was a partial compensation for faces revealed per unit time. In both Experiment 1 and Experiment 2, performance was consistent across rotational axis and directional conditions. In Experiment 3, the effect of object size was examined, in order to determine the extent to which angular velocity judgments are influenced by the tangential velocity of the faces. When the comparison cube's edges were half the length of the standard's, PSEs were elevated 18.5%. Taken together, these data suggest that observers are able to discriminate angular velocities with a competence near that for linear velocities. However, perceived angular rate is influenced by structural aspects of the stimuli. PMID- 2304814 TI - The perceptual interaction of graphical attributes: configurality, stimulus homogeneity, and object integration. AB - Researchers have proposed that graphical efficacy may be determined, in part, by the nature of the perceptual interactions that exist between attributes used to create graphical displays. One extreme type of interaction is integrality, in which two or more physical dimensions are represented as a single psychological dimension in the observer. An alternative type of interaction is configurality, in which a global emergent dimension is available to the observer in addition to the component attributes. Thirteen stimulus sets, each composed of attributes commonly used in the design of graphs, were submitted to the performance-based diagnostics of integrality and configurality. Analyses suggest a continuum of configurality among the present stimulus sets, with little evidence for integral graphical attributes. The configural pattern of results was more common when two identical dimensions were paired (homogeneous stimuli) than when two different dimensions were paired (heterogeneous stimuli). However, there was no evidence that pairs of dimensions belonging to a single object (object integration) were any more configural than dimensions belonging to different objects. Object integration was, however, consistently related to inefficient performance in tasks requiring the filtering of one of two component dimensions. PMID- 2304815 TI - Kinetic occlusion: further studies of the boundary-flow cue. AB - Previous work has demonstrated that human beings employ a processing assumption, the boundary-flow constraint, in perceiving the order of depth at an edge. Subjects perceive depth order of surfaces on the basis of the relative motions of an image boundary and a projected surface texture on either side of the boundary. In the present study, adult subjects viewed computer-generated kinematograms in which boundary-flow information provided the only cue for depth order. The results of Experiments 1 and 2 indicate that common motion between boundary and texture and differential motion between boundary and texture can independently generate the perception of ordered depths of surfaces. In Experiment 3, we examined the interaction of two processes involved in the extraction of depth order from boundary-flow displays: (1) the propagation of foreground and background surfaces from texture to boundary; and (2) the computation of depth order of surfaces on either side of the boundary. The results indicate that while the mechanism that computes depth from boundary-flow information functions reliably when the mean distance between texture and boundary is 8.1(0), surface propagation may be disrupted for distances of this magnitude. PMID- 2304816 TI - Visual field differences in the magnitude of the Oppel-Kundt illusion vary with processing time. AB - Three experiments were performed to investigate hemispheric differences in susceptibility to the Oppel-Kundt illusion presented tachistoscopically to the two visual hemifields. Experiment 1 used a successive comparison mode, in which 16 undergraduate students indicated whether the second of two successive extents looked shorter or longer than the first. Experiment 2 (20 under-graduates) and Experiment 3 (1 commissurotomy patient) required judgments of two extents presented simultaneously. The first experiment found no significant visual field differences, although females were more susceptible than males. In the second experiment, the illusion magnitude was greater in the left visual field, and in the third experiment, it was greater in the right visual field. Post hoc analyses resolve the conflicting results and show that in all three experiments, the susceptibility of the right hemisphere declined more than that of the left hemisphere during illusion processing. An interpretation is offered in terms of two parallel processes, one that is fast, uses feature extraction, and is performed more effectively in the left hemisphere, and one that is slow, uses visuospatial analysis to compute distances between parts of the illusion figure, and is performed more effectively in the right hemisphere. PMID- 2304819 TI - The abominable no-men: a cautionary tale. PMID- 2304818 TI - Relating attention to visual mechanisms. PMID- 2304817 TI - Neighborhood frequency effects in visual word recognition: a comparison of lexical decision and masked identification latencies. AB - Recent research suggests that the time to recognize a visually presented word may be a function of the frequencies of orthographically similar words. More precisely, recognition latencies and errors appear to increase significantly as soon as the stimulus word is orthographically similar to at least one other higher frequency word. This phenomenon, referred to as the neighborhood frequency effect, was subjected to further experimental testing, using a larger selection of words of varying frequency and length, and using a new experimental technique that proved to be extremely sensitive to such effects. The results provide additional support for earlier observations of neighborhood frequency effects. It is also demonstrated that clear word-frequency effects do obtain when neighborhood frequency is held constant. The results support activation-based accounts of the word-recognition process. PMID- 2304820 TI - Aesthetics and ethics: the implications of cosmetic surgery. PMID- 2304821 TI - Genetics and health care: a paradigm shift. PMID- 2304822 TI - Data manipulation: Dr. Factifuge meets the Three Stooges. PMID- 2304823 TI - An N of 1: syndrome letters in the New England Journal of Medicine. PMID- 2304824 TI - Coping strategies of selected physicians. PMID- 2304825 TI - Some observations concerning out-of-awareness mentation. PMID- 2304826 TI - Pediatric AIDS Advisory Committee Reports. Generations in jeopardy--responding to HIV infection in children, women and adolescents in New Jersey. PMID- 2304827 TI - Power in nursing practice gained through research. PMID- 2304828 TI - AJN writing contest winner. PMID- 2304829 TI - Review of research in nursing education. Volume III. PMID- 2304830 TI - Moral and ethical development research in nursing education. AB - Research in moral development is breaking into exciting new territory with the long overdue inclusion of the female perspective. Nursing education needs to be on the forefront of this cutting edge, seeking new ways to help students confront the difficult moral dilemmas they will face daily as members of the nursing profession. PMID- 2304831 TI - [The status of abortion in Scandinavian countries]. PMID- 2304832 TI - [An increased number of induced abortions in Denmark?]. PMID- 2304833 TI - [Stable number of abortions in Finland]. PMID- 2304834 TI - [Requirements for abortion conditions in Iceland]. PMID- 2304835 TI - [Continuous abortion debate in Norway]. PMID- 2304836 TI - [Increasing number of abortions in Sweden. Is it time for a sexology specialist?]. PMID- 2304837 TI - [The origin and evolution of viruses]. AB - This paper describes various hypotheses for the origin of viruses, prerequisites for the introduction of a virus into a host population, and the concerted evolution of virus and host. In general, viruses evolve through mutations and genetic recombinations. Selection pressure is exerted by various host defence mechanisms and possible ways of virus transmission. The virus variants showing a high reproduction rate without killing their host are most likely to be selected for. In addition, the viral infection vice versa exert a selection pressure on the host population resulting in the elimination of highly susceptible individuals and an increased number of resistant individuals. The apparent consequence is a tendency for the virus to be less virulent and the host to be more resistant. PMID- 2304838 TI - [Current cooperation concerning admission to and discharge from geriatric hospitals]. AB - A method of building bridges--in terms of therapy and care--between the life of the elderly before, during, and after a stay in hospital is described in this randomized, controlled study from a Copenhagen suburb. A project nurse employed by the City called at the Hospital each day and followed the members of this group concerning the need to gather information from primary care, discuss discharge with the patient and the nursing staff, co-ordinate possible supportive measures in the home, and immediately after the discharge to make a home visit to ensure continuity of care and treatment. PMID- 2304839 TI - [The helplessness of medicine. 2. A challenge for general medicine]. AB - In a first article the helplessness of modern medicine was presented and analyzed. This article discusses the role of general practice in preventing this helplessness as a medical and scientific discipline. The key to prevention is to analyze 1) which medical needs are relevant for the patients, and 2) what are the options of fulfilling these needs within the medical reality of today. General practice is a medical area where real life knowledge is estimated and available. General practitioners have experienced the inadequacy of the medical model where objectivity is superior, and therefore are developing new medical theories better suited for medical everyday problem solving. Medicine may be helped away from its present helplessness by general practice knowledge, provided that such knowledge is refined and developed and made scientifically reliable. Subjective knowledge may be transformed into science within new medical paradigms and by means of methodological tools borrowed from neighbouring human sciences. If medicine acknowledges its own helplessness, it may be treated by general practice contributions to a medical and scientific reorientation. PMID- 2304840 TI - A good night's crest. PMID- 2304841 TI - In the same boat? PMID- 2304842 TI - A litany of complaints. PMID- 2304843 TI - Confidentiality at stake. PMID- 2304844 TI - Hear today.... PMID- 2304846 TI - The cosmic crusaders. Interview by Andrew Cole. PMID- 2304845 TI - Dial 999 for confusion. PMID- 2304847 TI - Local heroine. Interview by Gill Crabbe. PMID- 2304848 TI - Management. Neighbourhood networks. PMID- 2304849 TI - Deep vein thrombosis. Threat to recovery. PMID- 2304850 TI - Reading between the lines. PMID- 2304851 TI - Coming unglued. PMID- 2304852 TI - Money rights. Hospital patients. PMID- 2304853 TI - Hepatitis B: more care, less scare. PMID- 2304855 TI - Motor through winter safely. PMID- 2304854 TI - Management. More than a support. PMID- 2304856 TI - Insurance at a premium. PMID- 2304857 TI - Stop-start negotiations. PMID- 2304858 TI - Womb service. PMID- 2304860 TI - Listeria--risk or hysteria? PMID- 2304861 TI - Resisting arrest. PMID- 2304859 TI - Training for the dole. PMID- 2304863 TI - What would Florence say? PMID- 2304862 TI - A vanishing species? PMID- 2304864 TI - Fair deal on appeal. The forgotten fifty thousand. PMID- 2304865 TI - Fair deal on appeal. Enigma variations. PMID- 2304866 TI - Pressure sore prevention--project improves practice. PMID- 2304867 TI - A little knowledge.... PMID- 2304868 TI - Information wanted. PMID- 2304869 TI - Making sense of ... x-ray precautions. PMID- 2304870 TI - Deep vein thrombosis. Methods of prevention. PMID- 2304871 TI - Spreading the word on breastfeeding. PMID- 2304872 TI - George--an elderly depressed patient. PMID- 2304873 TI - Money rights. Residents in homes. PMID- 2304874 TI - Nursing the NHS. PMID- 2304875 TI - Performance indicators. PMID- 2304876 TI - Nurse education. How to ... get the best from videotapes. PMID- 2304877 TI - Myocardial scintigraphy with 201thallium in pediatric cardiology: a review of 52 cases. AB - We report our experience of myocardial scintigraphy with 201thallium (201Tl) in 52 children, aged 4 days to 18 years, in which 80 studies were made primarily to demonstrate or exclude impaired myocardial perfusion. For analysis, the patients were divided into the following eight groups: group I, coronary artery malformations (five patients); group II, Kawasaki's syndrome (six patients); group III, arterial switch operation (seven patients); group IV, dilated cardiomyopathy (18 patients); group V, hypertrophic cardiomyopathy (four patients); group VI, myocardial dysfunction after surgery for congenital heart disease (five patients); group VII, pulmonary atresia (three patients); and group VIII, miscellaneous (four patients). Myocardial scintigraphy was performed with a planar or tomographic technique at rest or after exercise (four patients). Isotope-uptake defects, indicating impaired myocardial perfusion, were present in 14 patients, including small infants. Defects were seen in all groups except those with hypertrophic cardiomyopathy and pulmonary atresia. The absence of such defects in several of the patients with Kawasaki's syndrome was particularly valuable as it made coronary angiography unnecessary. In the other groups of patients myocardial scintigraphy was a valuable adjunct to other investigations. PMID- 2304879 TI - Single papillary muscle ("parachute valve") and double-orifice left ventricle in atrioventricular septal defect convergence of chordal attachment: surgical anatomy and results of surgery. AB - A review of 59 anatomical specimens and of the findings in 65 surgically repaired patients with atrioventricular septal defect (AVSD), revealed four patients with a single papillary muscle and 11 with a double-orifice left ventricle. A single papillary muscle of the left ventricle occurred in 1.7% (1 of 59) of the anatomical specimens, and 6% (4 of 65) of the surgical cases. A double orifice of the left ventricle was found in 13.6% (8 of 59) of the anatomical specimens, and 7.7% (6 of 65) of the surgical cases. A single papillary muscle was only seen in cases with a complete defect. Double orifice was associated with partial, complete, or intermediate type of defect, with the highest incidence in the intermediate forms: 40% (4 of 10) of the anatomical specimens and 22% (2 of 9) of the surgical cases. In the anatomical study the specimens, with either single papillary muscle or double-orifice left ventricle, appear to be variants of the same malformation characterized by convergence of chordal insertion and underdevelopment of the left lateral leaflet. Pathology belonging to this spectrum was seen in 15% of our autopsy specimens and 14% of the surgical cases. In the surgical series good operative results were obtained with a conservative approach in cases with a favorable surgical anatomy. PMID- 2304880 TI - Aortopulmonary window coexisting with tetralogy of Fallot: echocardiographic diagnosis. AB - Aortopulmonary window coexisting with tetralogy of Fallot (TF) was prospectively diagnosed by two-dimensional (2D) echocardiography and Doppler in an 18-month-old boy; the diagnosis was confirmed by cardiac catheterization and angiocardiography. Surgical correction was performed, but the patient died in the operating room from right ventricular dysfunction. The autopsy showed an adequate surgical repair, but the histologic examination of the lungs demonstrated severe pulmonary vascular disease, which was presumed to be the cause of death. PMID- 2304881 TI - Cerebral embolization from an inferior vena cava thrombus in tetralogy of Fallot. AB - Cerebrovascular accident (CVA) complicating cyanotic congenital heart disease (CCHD) is most frequently attributed to cerebral venous thrombosis, only rarely to in situ cerebral arterial thrombosis. Cerebrovascular accident due to paradoxical embolization from an inferior vena cava (IVC) thrombus in a patient with tetralogy of Fallot (TF) is described. This case is the first antemortem documentation of a venous embolic source that caused paradoxical embolization to the brain in a patient with CCHD, and illustrates the importance of noninvasive screening for a venous source of emboli in these patients. PMID- 2304878 TI - Endomyocardial biopsy in infants and children: experience in 60 patients. AB - In 60 children, aged between 1 month and 22 years (median 3.54 years) and with a body weight of 3-67 kg (median 12.6 kg), transvascular endomyocardial biopsy (EMB) was performed from the right (35 children) or left ventricle (30 children). The specimens were investigated by light and electron microscopy. There were three indications for biopsy: (1) poorly functioning, dilated left ventricle (seven patients with endocardial fibroelastosis, 16 with dilated cardiomyopathy, six from healing/healed or chronic myocarditis); (2) unexplained left ventricular hypertrophy (10 with hypertrophic cardiomyopathy, four with secondary hypertrophy, three with storage diseases); (3) to answer certain questions in eight children (four with hypoxic and two with cytoxic myocardial damage). Retrospectively, there were five nonindicated biopsies. There were no serious complications. Biopsies were diagnostic in 11.7% of cases, helpful in 71.7%, and of no help in 16.6%. Thus even in childhood endomyocardial biopsy is a diagnostic tool which can add useful information on the etiology or pathogenesis of an underlying myocardial disease. PMID- 2304882 TI - Pulmonary hypertension in type I glycogen storage disease. AB - Two cases of pulmonary hypertension associated with type I glycogen storage disease (type I GSD) are reported. Before the development of pulmonary hypertension, patient 1 had been treated with dietary therapy with nocturnal gastric-drip infusion and zyloric therapy. Patient 2 had received a shunt operation between the intestinal vein and inferior vena cava, as well as dietary therapy. Both patients died of progressive heart failure due to pulmonary hypertension despite many attempts at drug therapy. There was no evidence in either case of a disorder that could have been the cause of the pulmonary hypertension. In case 1, the autopsy revealed a vasoconstrictive type of pulmonary hypertension with plexiform vascular lesions. PMID- 2304884 TI - Emergency aortic balloon valvotomy in critical aortic stenosis of the neonate. PMID- 2304883 TI - Left ventricular thrombus following repair of truncus arteriosus. AB - A 6-month-old infant developed a left ventricular thrombus in association with low antithrombin-III activity following the repair of a truncus arteriosus. Conservative management was associated with spontaneous resolution of the clot. The significance of this association is discussed. PMID- 2304885 TI - Significance of the Doppler-derived gradient across a residual aortic coarctation. AB - Few data exist which address the significance of the Doppler gradient across a residual narrowing in older children who have had a coarctation repaired. Therefore, we evaluated 11 patients with repaired aortic coarctation with and without residual obstruction by Doppler echocardiography. The Doppler-derived transcoarctation pressure gradient correlated poorly with catheter-measured peak to-peak and catheter maximal instantaneous gradients when only the maximal velocity across the repair was utilized in the simplified Bernoulli equation, [r = 0.73, standard of error of the estimate (SEE) = 5.0 mmHg and r = 0.56, SEE = 7.6 mmHg, respectively]. However, when the precoarctation velocity was included in the simplified Bernoulli equation, the correlation between Doppler-derived and catheter-measured gradients became excellent. The maximal Doppler gradient correlated well with catheter peak-to-peak gradient (r = 0.95, SEE = 2.2 mmHg) and catheter maximal instantaneous gradient (r = 0.94, SEE = 3.2 mmHg). However, the maximal Doppler gradient slightly overestimated the catheter peak-to-peak gradient and underestimated the catheter maximal instantaneous gradient. The Doppler mean gradient showed excellent correlation with the catheter mean gradient (r = 0.97, SEE = 0.85 mmHg). Precoarctation velocities were generally twofold greater than published normals due to a spatial acceleration phenomenon. All subjects had residual hypoplasia of the transverse aorta such that its transverse diameter was 29% less than, and its cross-sectional area was 50% less than, the ascending and descending aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304886 TI - Effects of intravenous infusion of human prostate tissue substances in dogs. AB - Symptoms of postresection syndromes following transurethral prostatectomy have been associated with a transient increase in serum acid phosphatase due to intraoperative absorption of prostate tissue substances. Factors associated with postoperative syndromes include intraoperative absorption of irrigant solution, intraoperative blood loss, and intraoperative absorption of prostate tissue substance. An animal model was used in this study to determine the isolated physiologic effects of intravenous infusion of a saline prostate tissue extract using an infusion schedule comparable to that of transurethral prostate resection. Twenty-four animals received either normal saline infusion (control) or saline prostate tissue extract infusion (experimental). The experimental group showed a significant decrease in fibrinogen, platelet count, white blood count, activated clotting time, and plasma volume. These results suggest that the isolated effects of intravascular absorption of prostate tissue substances are due to disseminated intravascular coagulation, most likely resulting from tissue thromboplastin and activation of plasminogen. PMID- 2304887 TI - Radiolocalization of human prostate tumor in a mouse subrenal capsule model by monoclonal antibody TURP-27. AB - The subrenal capsule assay was used to determine if 125I-labeled anti-prostate monoclonal antibody TURP-27 could target human prostate tumor fragments implanted under the renal capsule of normal immunocompetent C57 BL/6 mice. Maximal binding and optimal tumor to non-tumor tissue ratios occurred within 24-48 hours postadministration of 125I-TURP-27. No significant localization was observed in mice bearing TURP-27 antigen-negative human colon tumor tissue implants or with an isotype-matched control monoclonal antibody. These preclinical data suggest that TURP-27 may have clinical application for imaging metastatic prostate tumors and further application in immunoconjugate and/or radiotherapy of prostate cancer. PMID- 2304888 TI - Family practice income averages $99,928. PMID- 2304889 TI - Be thankful for minor aches and pains. PMID- 2304890 TI - Tennis elbow and life-style factors. PMID- 2304891 TI - Splints versus casts. PMID- 2304892 TI - Amperozide: the pharmacological profile of a novel antipsychotic agent. PMID- 2304893 TI - Effects of amperozide, a putative antipsychotic drug, on rat midbrain dopamine neurons recorded in vivo. AB - The effect of the putative antipsychotic compound amperozide on the electrical activity of single identified midbrain dopamine (DA) neurons was investigated in the chloral hydrate anesthetized male rat. While the activity of DA cells in the substantia nigra was unaffected, DA neurons of the ventral tegmental area (VTA), the origin of the mesolimbocortical DA system, were affected in either of two ways: 1) increased firing rate and burst firing, i.e. an excitation, or 2) regularization of the firing pattern. Reversible cold inactivation of the medical prefrontal cortex (PFC) induced a pacemaker-like firing of VTA-DA cells, an effect blocked by amperozide in the cells excited by the drug. Cells responding with a regularization were not protected against the effect of PFC inactivation. These different effects of amperozide, which may in part be mediated by 5-HT2 receptor blockade, suggest an antipsychotic activity of amperozide, particularly in schizophrenia with negative symptoms. PMID- 2304894 TI - Amperozide and emotional behaviour. AB - The new putatively antipsychotic drug amperozide is characterized pharmacologically by a specific limbic mode of action. Thus amperozide is a potent antagonist of muricidal behaviour (ED50 = 0.16 mg/kg) as well as aggression between isolated male mice. Although amperozide displays anxiolytic properties in Vogel's conflict test as well as an antidepressive effect in the despair test, the drug does not interfere with motor coordination or cause sedation (ED50 greater than 50 mg/kg). These results could make amperozide very interesting as an antipsychotic drug in the clinic, with effect on both positive and negative symptoms. PMID- 2304895 TI - The effect of amperozide on uptake and release of [3H]-dopamine in vitro from perfused rat striatal and limbic brain areas. AB - Amperozide, a putatively antipsychotic drug, was studied for its effects on uptake and release of [3H]-dopamine in rat brain in vitro. Amperozide inhibited uptake of [3H]-dopamine in striatal chopped tissue in vitro with an IC50 of 18 microM. It also increased basal release of [3H]-dopamine from perfused rat striatal and limbic tissue in vitro at concentrations above 5 microM. Release of [3H]-dopamine from perfused rat striatal and limbic tissue stimulated with 5 microM amphetamine, was inhibited by 1 microM amperozide to 46%. No significant difference was found for the effect of amperozide on in vitro release of [3H] dopamine from corpus striatum compared to tissue from limbic brain regions; neither on basal release nor an amphetamine-stimulated release of dopamine. PMID- 2304896 TI - Amperozide--effect on prolactin release in the rat. AB - Amperozide, a new putatively antipsychotic drug was investigated for its effect on prolactin release in the rat. A significant decrease in the plasma concentration of prolactin was found at 30 minutes after treatment with amperozide. However, there was no effect of amperozide on prolactin release from isolated pituitary cells. These results suggest that there is no direct effect of amperozide on the pituitary lactotrophs and that the attenuation of prolactin secretion in vivo is mediated at a higher level. PMID- 2304897 TI - Erythrocyte metallothionein as an index of zinc status in humans. AB - Metallothionein concentrations in erythrocyte lysates derived from human subjects were measured by an ELISA procedure. IgG obtained from serum of sheep injected with human metallothionein 1 was used in this competitive assay. Subjects were fed a semipurified zinc-deficient diet (0.7 mg of zinc per kg of diet) for an 8 day depletion period after 3 days of acclimation. Fasting plasma zinc concentrations were reduced approximately 7%. Metallothionein in the erythrocyte lysates was significantly decreased to 59% of the initial level by the end of the depletion period. Supplementation of these depleted subjects with zinc (50 mg) did not increase erythrocyte metallothionein levels within 24 hr. Daily supplementation of control subjects with zinc (50 mg/day) increased erythrocyte metallothionein to a 7-fold maximum within 7 days. These levels were reduced by 61% within 14 days after zinc supplementation was terminated. Incubation of rat [35S]metallothionein with human erythrocyte lysate showed a time-dependent increase in 35S soluble in 20% trichloroacetic acid, indicating degradation of the labeled protein, presumably via protease activity in the lysate. It is proposed that zinc supplementation induces erythrocyte metallothionein during erythropoiesis and that low zinc intake decreases synthesis and/or accelerates degradation of the protein in reticulocytes/erythrocytes. Metallothionein levels in erythrocytes may provide a useful index upon which to assess zinc status in humans. PMID- 2304899 TI - Binding of cystatin C to C4: the importance of sense-antisense peptides in their interaction. AB - Hydropathic anticomplementarity of amino acids indicates that peptides derived from complementary DNA strands may form amphiphilic structures and bind one another. By using this concept, we have found that the antisense peptide Ser-Tyr Asp-Leu complementary to the segment Gln-Ile-Val-Ala-Gly (residues 55-59) in cystatin C (an inhibitor of cysteine proteases) is located at positions 611-614 of the beta chain of human C4, the fourth component of complement. Here we describe and characterize the specific interaction between cystatin C and C4 by ligand affinity chromatography and ELISA. Interaction between the two native proteins was mimicked on replacement of one of them with the corresponding sense antisense peptide coupled to a carrier protein, and the binding was inhibited by these synthetic peptides in solution. Through the interaction with C4, cystatin C may play a regulatory role in complement activation that might be of particular importance at tissue sites where both proteins are produced by macrophages. PMID- 2304898 TI - Identification of the HeLa tumor-associated antigen, p75/150, as intestinal alkaline phosphatase and evidence for its transcriptional regulation. AB - Prior studies identified a cell-surface antigen, p75/150, that exclusively associated with the tumorigenic phenotype of the HeLa parent and the tumorigenic phenotype of the HeLa parent and the tumorigenic segregants of suppressed, nontumorigenic HeLa x human fibroblast cell hybrids. Candidate p75/150 cDNA clones were isolated from a D98/AH.2 (HeLa) cDNA library using oligonucleotide probes derived from p75/150 partial peptide sequence data. A data base search revealed close similarity of p75/150 with intestinal alkaline phosphatase (IAP) [Berger, J., Garantini, E., Hua, J. C. & Udenfriend, S. (1987) Proc. Natl. Acad. Sci. USA 84, 695-698]. We demonstrate that p75/150 is identical to HeLa IAP by the following criteria: (i) 47/49 amino acid identity of p75 peptide sequence with IAP, (ii) restriction maps for the p75/150 candidate cDNA clone and IAP are identical, (iii) partial DNA sequence analysis of p75/150 candidate cDNA clones revealed complete nucleotide identity with IAP, except for a single nucleotide substitution in the 5' untranslated region, (iv) transfection of a p75/150 cDNA expression vector into the nontumorigenic hybrid, CGL1, yielded p75/150 antibody positive transfectants that also expressed partially heat-resistant alkaline phosphatase activity. Northern blot analysis demonstrated that high levels of HeLa IAP mRNA were expressed in D98/AH.2 and the tumorigenic segregant CGL4; however, no mRNA was detected in CGL1. Nuclear run-on analyses indicate that HeLa IAP mRNA expression in the HeLa x fibroblast hybrids is regulated at the level of transcription initiation. Furthermore, evidence is discussed supporting the involvement of a chromosome 11 tumor suppressor locus in the regulation of HeLa IAP gene expression. PMID- 2304900 TI - Antibodies against membrane interleukin 1 alpha activate accessory cells to stimulate proliferation of T lymphocytes. AB - Some monoclonal antibodies (mAbs) against interleukin (IL) 1 alpha have been found to activate antigen-presenting cells (APC, human peripheral blood monocytes and B lymphocytes), so that unstimulated T lymphocytes cultured with them are induced to proliferate and secrete IL-2. Control mAbs of the same isotypes and mAbs against IL-1 beta do not activate APC. In the absence of APC, mAbs against IL-1 alpha do not induce proliferation of T lymphocytes. Mitomycin C-treated activated APC still induce T-cell proliferation. Proliferation of T lymphocytes cannot be induced by culture supernatants and requires contact with APC activated by mAbs against IL-1 alpha. The observations imply that surface membrane IL-1 alpha can function as a triggering molecule on APC, which could play an important role in the initiation of immune responses by T lymphocytes. PMID- 2304901 TI - Identification and mapping of a common proviral integration site Fli-1 in erythroleukemia cells induced by Friend murine leukemia virus. AB - Friend murine leukemia virus (F-MuLV) induces erythroleukemia when inoculated into newborn BALB/c or NIH/Swiss mice. We have molecularly cloned F-MuLV host cell DNA junction fragments from an erythroleukemia cell line induced by F-MuLV to identify cellular genes involved in the leukemogenic process. One particular proviral integration site, Fli-1, is rearranged in 75% (9/12) of independently isolated erythroleukemia cell lines derived from either BALB/c or NIH/Swiss mice inoculated at birth with F-MuLV. Other hematopoietic neoplasms induced by F-MuLV, including myeloid (granulocytic) and lymphoid tumors, did not show rearrangements of the Fli-1 locus. Similarly, none of 35 erythroleukemia cell lines induced by the Friend virus complexes (FV-A and FV-P) was rearranged at the Fli-1 locus. In contrast, no rearrangements were detected at the Sfpi-1 locus, a preferred site of integration in either FV-P- or FV-A-induced leukemias. Using recombinant inbred mice, the Fli-1 locus was situated on mouse chromosome 9 close to the cellular protooncogene c-ets-1. DNA and RNA analysis suggests, however, that Fli 1 is different from ets-1. Thus, Fli-1 appears to define a distinct locus specifically involved in the induction of erythroid leukemias by F-MuLV. PMID- 2304902 TI - Protective immunogenicity of two synthetic peptides selected from the amino acid sequence of Bordetella pertussis toxin subunit S1. AB - Two peptides, corresponding to amino acids 1-17 and 169-186 of the amino acid sequence of pertussis toxin (PT) subunit S1, were synthesized and coupled to the diphtheria toxin cross-reactive mutant protein CRM 197 and evaluated for immunogenicity and protective capacity against PT challenge in vivo. The peptide CRM conjugates induced high antibody titers against native toxin in mice (BALB/c, C57/Black, and outbred NMRI) as measured by ELISA. Upon PT challenge (0.5 microgram of toxin) of the NMRI mice, the CRM conjugates of peptides 1-17 and 169 186 fully protected the mice from PT-induced leukocytosis. Immunization with the corresponding bovine serum albumin conjugates of these two peptides also fully protected mice. Rabbit antiserum to the peptide 1-17-CRM conjugate was highly efficient in inhibiting the ADP-ribosylating activity of PT but did not neutralize the clustering effect of PT on Chinese hamster ovary cells. In contrast, the rabbit antiserum raised against the peptide 169-186-CRM conjugate neutralized the clustering effect of PT on Chinese hamster ovary cells but did not inhibit the enzymatic activity of PT. Peptide 169-186-CRM conjugates mimic the immunoglobulin binding properties of PT and also cause clustering of Chinese hamster ovary cells. The CRM conjugates of these two peptides constitute a synthetic pertussis vaccine candidate with the ability to provide a chemically well-defined, safe, and efficient pertussis vaccine. PMID- 2304903 TI - Use of nonradioactive 2-deoxyglucose to study compartmentation of brain glucose metabolism and rapid regional changes in rate. AB - A method is presented for measuring rapid changes in the rate of glucose phosphorylation in mouse brain with nonradioactive 2-deoxyglucose (DG). After times as short as 1 min after DG injection, the mouse is frozen rapidly, and selected brain regions are analyzed enzymatically for DG, 2-deoxyglucose 6 phosphate (DG6P), and glucose. The rate of glucose phosphorylation can be directly calculated from the rate of change in DG6P, the average levels of DG and glucose, and a constant derived from direct comparison of the rate of changes in glucose and DG6P after decapitation. Experiments with large brain samples provided evidence for a 2% per min loss of DG6P and at least two compartments differing in their rates of glucose metabolism, one rapidly entered by DG with glucose phosphorylation almost double that of average brain and another more slowly entered with a much lower phosphorylation rate. The method is illustrated by changes in phosphorylation within 2 min after injection of a convulsant or an anesthetic and over a 48-min time course with and without anesthesia. The sensitivity of the analytical methods can be amplified as much as desired by enzymatic cycling. Consequently, the method is applicable to very small brain samples. Examples are given for regions with volumes of 5 x 10(-4) microliters, but studies with samples as small as single large cell bodies are feasible. PMID- 2304904 TI - Observations of reaction intermediates and the mechanism of aldose-ketose interconversion by D-xylose isomerase. AB - Crystallographic studies of D-xylose isomerase (D-xylose ketol-isomerase, EC 5.3.1.5) incubated to equilibrium with substrate/product mixtures of xylose and xylulose show electron density for a bound intermediate. The accumulation of this bound intermediate shows that the mechanism is a non-Michaelis type. Carrell et al. [Carrell, H. L., Glusker, J. P., Burger, V., Manfre, F., Tritsch, D. & Biellmann, J.-F. (1989) Proc. Natl. Acad. Sci. USA 86, 4440-4444] and the present authors studied crystals of the enzyme-substrate complex under different conditions and made different interpretations of the substrate density, leading to different conclusions about the enzyme mechanism. All authors agree that the bound intermediate of the sugar is in an open-chain form. It is suggested that the higher-temperature study of Carrell et al. may have produced an equilibrium of multiple states, whose density fits poorly to the open-chain substrate, and led to incorrect interpretation. The two groups also bound different closed-ring sugar analogues to the enzyme, but these analogues bind differently. A possible explanation consistent with all the data is that the enzyme operates by a hydride shift mechanism. PMID- 2304905 TI - Induction of acetylcholine receptor alpha-subunit gene expression in chicken myotubes by blocking electrical activity requires ongoing protein synthesis. AB - The level of acetylcholine receptor alpha-subunit mRNA in primary cultures of chicken myotubes increases when the spontaneous electrical activity of the myotube is suppressed by the sodium channel blocker tetrodotoxin. This increase was prevented by two translational inhibitors: cycloheximide and anisomycin. Neither the basal level of alpha-subunit mRNA nor that of muscle-specific creatine phosphokinase mRNA was affected by these inhibitors. In contrast, cycloheximide potentiated the limited increase of alpha-subunit mRNA levels evoked by the neuropeptide calcitonin gene-related peptide. The high level of alpha-subunit mRNA elicited by tetrodotoxin treatment did not persist after subsequent addition of cycloheximide in the presence of tetrodotoxin, indicating that the continuous synthesis of protein factor(s) is necessary for this regulation. Moreover, cycloheximide decreased the high level of alpha-subunit mRNA present at early stages of in vitro maturation of muscle primary cultures without blocking the further increase of the muscle-specific creatine phosphokinase mRNA. Implications of the requirement for constant synthesis of protein factors on the induction of muscle-specific gene expression by blocking myotube electrical activity are discussed. PMID- 2304906 TI - Callosal projections in rat somatosensory cortex are altered by early removal of afferent input. AB - During the first postnatal week, the distribution of callosal projection neurons in the rat somatosensory cortex changes from a uniform to a discontinuous pattern. To determine if this change is influenced by afferent inputs to the somatosensory cortex, the effect of both early unilateral infraorbital nerve section and unilateral removal of the dorsal thalamus on the distribution of callosal projections in rat somatosensory cortex was examined. One month after either of the above manipulations at birth, the tangential distribution of callosal projections in the somatosensory cortex was examined using the combined retrograde and anterograde transport of horseradish peroxidase. Both manipulations alter the distribution of callosal projection neurons and terminations in the somatosensory cortex. After infraorbital nerve section, the distribution of callosal projections is altered in the contralateral primary somatosensory cortex. The abnormalities observed are consistent with the altered distribution of thalamocortical projections. In addition, consistent abnormalities were observed in the pattern of callosal projections of the second somatosensory area of both hemispheres. Most notably, they are absent in a portion of the region that contains the representation of the mystacial vibrissae and sinus hairs in this area. Thalamic ablation resulted in highly aberrant patterns of callosal projections in the somatosensory cortex on the operated side, where abnormal bands and clusters of callosal projections were observed in apparently random locations. These results are interpreted as evidence that both peripheral and central inputs influence the maturational changes in the distribution of callosal projection neurons. PMID- 2304907 TI - Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse. AB - Eighteen variants recovered from specific locus mutation rate experiments involving the mutagen chlorambucil were subjected to several genetic and molecular analyses. Most mutations were found to be homozygous lethal. Because lethality is often presumptive evidence for multilocus-deletion events, 10 mutations were analyzed by Southern blot analysis with probes at, or closely linked to, several of the specific locus test markers, namely, albino (c), brown (b), and dilute (d). All eight mutations (two c; three b; two d; and one dilute short ear [Df(d se)]) that arose in post-spermatogonial germ cells were deleted for DNA sequences. No evidence for deletion of two d-se region probes was obtained for the remaining two d mutations that arose in stem-cell spermatogonia. Six of the primary mutants also produced low litter sizes ("semisterility"). Karyotypic analysis has, to date, confirmed the presence of reciprocal translocations in four of the six. The high frequency of deletions and translocations among the mutations induced in post-spermatogonial stages by chlorambucil, combined with its overall high efficiency in inducing mutations in these stages, should make chlorambucil mutagenesis useful for generating experimentally valuable germ-line deletions throughout the mouse genome. PMID- 2304908 TI - Pyrimethamine: an approach to the development of a male contraceptive. AB - With the human population of the world currently more than 5.2 billion and growing at an explosive rate, the need for additional forms of readily available contraception appears paramount. To date, contraception techniques in the male have been very limited. The present study demonstrates the ability of pyrimethamine (PYR) to cause spermatogenic arrest and male infertility in mice in a dose-dependent manner. Furthermore, upon cessation of drug administration all animals returned to normal fertility status. It is also suggested that the action of PYR is due to its antifolate action. Thus, PYR represents another approach toward development of a male contraceptive. PMID- 2304909 TI - Focal accumulation of an apolipoprotein B-based synthetic oligopeptide in the healing rabbit arterial wall. AB - The functions of surface-accessible domains of apolipoprotein (apo) B, the protein moiety of low density lipoprotein (LDL), are unknown, aside from the LDL receptor-binding domain, which lies toward the carboxyl-terminal end of apoB. Since LDL accumulation in arterial lesions does not depend on recognition of LDLs by a cell-surface receptor, we synthesized an oligopeptide with the sequence of the trypsin-accessible domain of apoB that lies closest to the amino-terminal end of the protein and compared its biological activity to that of another synthetic oligopeptide with the sequence of the heparin- and apoB/apoE receptor-binding domains of apoE. (Tyrosine was added at the amino-terminal end of each peptide to facilitate radiolabeling.) The 18-amino acid apoB-based peptide included residues 1000-1016 of apoB, for which no function has been previously described. In radioautographs, the 125I-labeled peptide accumulated focally at the healing edges of regenerating endothelial islands in the balloon-catheter deendothelialized rabbit aorta. In contrast, the 21-residue apoE-based peptide, which included residues 129-148 of apoE, accumulated diffusely and uniformly throughout the deendothelialized areas of the aorta. The data show that focal binding of the apoB-based peptide can delineate arterial lesions and suggest that this arterial wall-binding domain of apoB mediates accumulation of LDLs in arterial lesions. PMID- 2304911 TI - Minimal model for signal-induced Ca2+ oscillations and for their frequency encoding through protein phosphorylation. AB - In a variety of cells, hormonal or neurotransmitter signals elicit a train of intracellular Ca2+ spikes. The analysis of a minimal model based on Ca2(+) induced Ca2+ release from intracellular stores shows how sustained oscillations of cytosolic Ca2+ may develop as a result of a rise in inositol 1,4,5 trisphosphate (InsP3) triggered by external stimulation. This rise elicits the release of a certain amount of Ca2+ from an InsP3-sensitive intracellular store. The subsequent rise in cytosolic Ca2+ in turn triggers the release of Ca2+ from a second store insensitive to InsP3. In contrast to the model proposed by Meyer and Stryer [Meyer, T. & Stryer, L. (1988) Proc. Natl. Acad. Sci. USA 85, 5051-5055], the present model, which contains only two variables, predicts the occurrence of periodic Ca2+ spikes in the absence of InsP3 oscillations. Such results indicate that repetitive Ca2+ spikes evoked by external stimuli do not necessarily require the concomitant, periodic variation of InsP3. The model is closely related to that proposed by Kuba and Takeshita [Kuba, K. & Takeshita, S. (1981) J. Theor. Biol. 93, 1009-1031] for Ca2+ oscillations in sympathetic neurones, based on Ca2(+)-induced Ca2+ release. We extend their results by showing the minimal conditions in which the latter process gives rise to periodic behavior and take into account the role of the rise in InsP3 caused by external stimulation. The analysis further shows how signal-induced Ca2+ oscillations might be effectively encoded in terms of their frequency through the phosphorylation of a cellular substrate by a protein kinase activated by cytosolic Ca2+. PMID- 2304912 TI - A time-dependent bacterial bioluminescence emission spectrum in an in vitro single turnover system: energy transfer alone cannot account for the yellow emission of Vibrio fischeri Y-1. AB - Yellow fluorescent protein (YFP), which has a bound FMN, was isolated from the marine bacterium Vibrio fischeri strain Y-1b. Its presence in a luciferase [alkanal monooxygenase (FMN-linked); alkanal, reduced-FMN:oxygen oxidoreductase (1-hydroxylating, luminescing), EC 1.14.14.3] reaction mixture causes a striking color change, and an increase in bioluminescence intensity, as well as a faster rate of intensity decay, so that the quantum yield is not changed. The emission spectrum shows two distinct color bands, one at 490 nm attributed to the unaltered emission of the luciferase system, the other peaking in the yellow around 540 nm due to YFP emission. The kinetics of the two color bands differ, so the spectrum changes with time. The yellow emission reaches its initial maximum intensity later than the blue, and then both blue and yellow emissions decay exponentially with nearly the same pseudo-first-order rate constants, linearly dependent on [YFP] (from 0.01 sec-1 with no YFP to a maximum of approximately 0.1 sec-1 at 4 degrees C) but exhibiting a saturation behavior. The data can be interpreted by assuming the interaction of YFP with the peroxyhemiacetal intermediate in the luciferase reaction to form an unstable new complex whose breakdown gives the yellow emitter in its excited state. This simple model fits well the data at [YFP] less than 15 microM. The results indicate that a single primary excited state cannot be responsible for the blue and the yellow emissions. PMID- 2304913 TI - Rapid morphological fusion of severed myelinated axons by polyethylene glycol. AB - We are able to morphologically fuse the severed halves of an invertebrate myelinated axon by application of polyethylene glycol (PEG) to closely apposed cut ends. Morphological fusion of the medial giant axon (MGA) of the earthworm Lumbricus terrestris is defined as axoplasmic and axolemmal continuity in serial longitudinal sections of MGAs taken through the fusion site as viewed with light or electron microscopes. Morphological continuity is also shown by the transfer of Lucifer yellow dye between apposed MGA segments fused with PEG, but not between apposed MGA segments in normal or hypotonic saline without PEG application. PEG-induced MGA fusion rates can be as high as 80-100% with an appropriate choice of PEG concentration and molecular mass, tight apposition and careful alignment of the cut ends, and treatment with hypotonic salines containing reduced calcium and increased magnesium. A variant of this technique might produce rapid repair of severed mammalian-myelinated axons. PMID- 2304910 TI - Intestinal brush border membrane Na+/glucose cotransporter functions in situ as a homotetramer. AB - The functional unit molecular size of the intestinal brush border membrane-bound Na+/glucose cotransporter was determined by radiation inactivation. Purified brush border membrane vesicles preserved in cryoprotectant buffer were irradiated (-135 degrees C) with high-energy electrons from a 13-MeV (1 eV = 1.602 x 10(-19) J) linear accelerator at doses from 0 to 70 Mrad (1 rad = 0.01 Gy). After each dose, the cotransporter was investigated with respect to (i) Na(+)-dependent transport activity and (ii) immunologic blot analysis with antibodies against the cloned rabbit intestinal cotransporter. Increasing radiation decreased the maximal Na(+)-dependent cotransporter activity Jmax without affecting apparent Km. The size of the transporting functional unit was 290 +/- 5 kDa. Immunologic blot analysis of brush border membranes gave a single band of Mr 70,000, which decreased in intensity with increased radiation dose and gave a target size of 66 +/- 11 kDa. We conclude that activity of the intestinal Na+/glucose cotransporter in situ in the brush border membrane requires the simultaneous presence of four intact, independent, identical subunits arranged as a homotetramer. PMID- 2304914 TI - Arrangement of subunits and domains within the Octopus dofleini hemocyanin molecule. AB - Native Octopus dofleini hemocyanin appears as a hollow cylinder in the electron microscope. It is composed of 10 polypeptide subunits, each folded into seven globular oxygen-binding domains. The native structure reassociates spontaneously from subunits in the presence of Mg2+ ions. We have selectively removed the C terminal domain and purified the resulting six-domain subunits. Although these six-domain subunits do not associate efficiently at pH 7.2, they undergo nearly complete reassociation at pH 8.0. The resulting molecule looks like the native cylindrical whole molecule but lacks the usual fivefold protrusions into the central cavity. Partially reassociated mixtures show dimers of the subunit that have a characteristic parallelogram shape when lying flat on the electron microscope grid, and a "boat" form in side view. Removal of the C-terminal domain from monomers results in the removal of two characteristically placed domains in the dimers. These observations allow the development of a model for the arrangement of the subunits within the whole molecule. The model predicts exactly the views seen in the electron microscope of both whole molecule and dimeric intermediates. PMID- 2304915 TI - Functional dissection of a mouse ribosomal protein promoter: significance of the polypyrimidine initiator and an element in the TATA-box region. AB - All of the mammalian ribosomal protein (rp) genes examined to date initiate transcription with high precision despite the fact that they do not contain a well-defined TATA box. The initiation sites are situated within polypyrimidine tracts that are flanked by both upstream and intragenic promoter elements. In the TATA-box region of each rp promoter, there is a functionally critical element with nuclear factor binding specificity that is distinct from that of a conventional TATA box. To understand how the various elements contribute to rp promoter function, we have used site-specific mutagenesis-transfection protocols and factor binding analyses to evaluate the significance of the polypyrimidine initiator and the TATA-box counterpart for efficient and accurate transcription of the rpS16 gene. Our results indicate (i) that the polypyrimidine initiator sequence critically defines the position of the transcriptional start site, whereas a much less specific sequence is sufficient to satisfy the efficiency requirement; (ii) that an uninterrupted stretch of pyrimidines in the initiator region is not necessary for efficient transcription of rpS16 gene; and (iii) that the TATA-box counterpart or even a substituted conventional TATA box primarily influences promoter efficiency. The great diversity of promoter design, which is becoming evident as more RNA polymerase II promoters are being carefully dissected, suggests that the requirements for building a functional initiation complex may be much more flexible than was previously appreciated. PMID- 2304916 TI - Maize chloroplast RNA polymerase: the 180-, 120-, and 38-kilodalton polypeptides are encoded in chloroplast genes. AB - Prominent polypeptides with apparent molecular masses of 180, 120, 85, and 38 kDa are found in an extensively purified preparation of maize chloroplast DNA dependent RNA polymerase that retains the capacity to initiate transcription of the cloned chloroplast gene rbcL correctly and the requirement for a supercoiled DNA template for specific and active transcription. Amino-terminal amino acid sequences of the 180-, 120-, and 38-kDa polypeptides have been determined and found to correspond precisely to the sequences deduced from the 5' ends of the maize chloroplast rpoC2, rpoB, and rpoA genes, respectively. These experiments show that these chloroplast rpo genes encode the prominent polypeptides in the highly enriched maize chloroplast RNA polymerase preparation and support the conclusion that these polypeptides are functional components of the enzyme. The rpoB, rpoC1, and rpoC2 genes have been mapped on the maize chloroplast chromosome. PMID- 2304917 TI - Carcinoembryonic antigen functions as an accessory adhesion molecule mediating colon epithelial cell-collagen interactions. AB - We have previously shown that a human colon carcinoma cell line (SW1222) expresses a collagen receptor recognizing the Arg-Gly-Asp tripeptide sequence found in collagen. This receptor mediates the cellular attachment to collagen and, subsequently, the glandular differentiation seen in a three-dimensional collagen gel culture. In a search to identify cell surface molecules mediating the adhesion and differentiation of SW1222 cells, we have screened a panel of monoclonal antibodies recognizing epithelial cell surface determinants for their ability to inhibit the collagen binding of SW1222 cells. We have found that four monoclonal antibodies recognizing the 180-kDa carcinoembryonic antigen (CEA) glycoprotein and other members of the CEA family inhibited (up to 87%) the binding of SW1222 cells to type I collagen matrix. Using a cell attachment assay, we have not detected any direct collagen binding of either purified CEA or another CEA-expressing human colon carcinoma cell line (LS174T). These data suggest that CEA is not a collagen-binding protein itself but is likely to be associated with the functional Arg-Gly-Asp collagen receptor expressed by SW1222 cells. We suggest that CEA may function as an accessory molecule, controlling the functional activity of the SW1222 collagen receptor. PMID- 2304918 TI - Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination. AB - Retroviruses contain two complete viral genomic RNAs in each virion. A system to study in a single round of replication the products of virions with two different genomic RNAs was established. A spleen necrosis virus-based splicing vector containing both the neomycin-resistance gene (neo) and the hygromycin B phosphotransferase gene (hygro) was used. Two frameshift mutants were derived from this vector such that the neo and the hygro genes were inactivated in separate vectors. Thus, each vector confers resistance to only one selection. The vectors with frameshift mutations were separately propagated and were pooled to infect DSDh helper cells. Doubly resistant cell clones were isolated, and viruses produced from these clones were used to infect D17 cells. This protocol allowed virions containing two different genomic RNAs (heterozygotes) to complete one round of retroviral replication. The molecular nature of progeny that conferred resistance to single or double selection and their ratio were determined. Our data demonstrate that each infectious heterozygous virion produces only one provirus. The rate of retroviral recombination is approximately 2% per kilobase per replication cycle. Recombinant proviruses are progeny of heterozygous virions. PMID- 2304920 TI - Contraction of neuronal branching volume: an anatomic correlate of Pavlovian conditioning. AB - Associative memory of the mollusc Hermissenda crassicornis, previously correlated with changes of specific K+ currents, protein phosphorylation, and increased synthesis of mRNA and specific proteins, is here shown to be accompanied by macroscopic alteration in the structure of a single identified neuron, the medial type B photoreceptor cell. Four to five days after training, terminal arborizations of B cells iontophoretically injected with Ni2+ ions and then treated with rubeanic acid were measured with charge-coupled device (CCD) digitized pseudocolor images of optical sections under "blind" conditions. Boundary volumes enclosing medial-type B-cell arborizations from classically conditioned animals were unequivocally reduced compared with volumes for naive animals or those trained with unpaired stimuli. Branch volume magnitude was correlated with input resistance of the medial type B-cell soma. Such associative learning-induced structural changes may share function with "synapse elimination" described in developmental contexts. PMID- 2304919 TI - Dynamics of myoglobin: comparison of simulation results with neutron scattering spectra. AB - Molecular dynamics simulations are used to calculate the incoherent neutron scattering spectra of myoglobin between 80 K and 325 K and compared with experimental data. There is good agreement over the entire temperature range for the elastic, quasi-elastic, and inelastic components of the scattering. This provides support for the accuracy of the simulations of the internal motions that make the dominant contributions to the atomic displacements on a time scale of 0.3-100 ps (100-0.3 cm-1). Analysis of the simulations shows that at low temperatures a harmonic description of the molecule is appropriate and that the molecule is trapped in localized regions of conformational space. At higher temperatures the scattering arises from a combination of vibrations within wells (substates) and transitions between them; the latter contribute to the quasi elastic scattering. PMID- 2304922 TI - Interactions of nimodipine and cocaine on endogenous catecholamines in the squirrel monkey. AB - The effects of nimodipine on the cocaine-induced alterations in blood pressure, heart rate, and plasma catecholamines were studied in the squirrel monkey. Cocaine in intravenously administered doses of 0.5, 1, and 2 mg/kg produced significant increases in blood pressure and significant decreases in heart rate. These cardiovascular changes were associated with transient episodes of arrhythmias and with significant increases in plasma concentrations of dopamine, epinephrine, and norepinephrine. Nimodipine, 1 micrograms/kg/min for 5 min administered intravenously 5 min after cocaine, corrects the cardiovascular and plasma catecholamine concentration changes induced by this alkaloid. The same dose of nimodipine administered 5 min before cocaine prevents elevations of blood pressure. Plasma catecholamine increments are also prevented except for the highest dose of cocaine. Cardiovascular changes induced by cocaine administration in the squirrel monkey are temporally associated with significant increments in plasma catecholamines. Administration of nimodipine prevents or minimizes these endocrine and physiologic changes. PMID- 2304921 TI - Soluble antigen abrogates the appearance of anti-protein IgG1-forming cell precursors during primary immunization. AB - The anti-human serum albumin (HSA) B-cell repertoire of C57BL/6 mice was examined by culturing splenocytes at limiting dilution following polyclonal stimulation with Escherichia coli lipopolysaccharide and a lymphokine mixture. The frequency of anti-HSA precursors was determined before and after immunization with alum precipitated HSA and 10(9) killed Bordetella pertussis organisms, by submitting clonal supernatants to an ELISA. Anti-HSA IgG1-forming precursors were rare in unimmunized spleens, representing approximately equal to 1 in 500,000 splenocytes or only approximately equal to 100 cells per spleen. Between day 5 and day 7 after immunization, this figure increased to approximately equal to 20,000 cells per spleen. Over the following 3 weeks, there was a progressive increase in the mean optical density generated in the clonal ELISA, presumably due to affinity maturation of the B-cell population. When freshly deaggregated HSA was injected before or even up to 4 days after challenge immunization, the appearance of anti HSA IgG1-forming cell precursors was largely prevented. The effect was most marked with 5 mg or 1 mg of soluble HSA, but impressive partial effects could be seen with as little as 10 micrograms of HSA if administered before challenge immunization. Most of the few clones seen after the higher doses of the toleragen appeared to make antibody of low affinity. The capacity to influence the B-cell pool by soluble antigen administered just 1-2 days before the sudden appearance of IgG1 precursors argues against the totality of the effect being due to T-cell mediated suppression and in favor of a direct effect on B cells. PMID- 2304923 TI - Effect of chronic caffeine administration on theophylline concentrations required to produce seizures in rats. AB - Caffeine as well as the antiasthmatic drug theophylline can cause seizures when administered to humans or animals in excessive doses. Studies on rats have shown rapid development of functional tolerance to caffeine-induced seizures whereas repeated pretreatment with theophylline had no significant effect on the theophylline concentrations required to produce seizures. The purpose of this investigation was to determine whether chronic exposure to caffeine can affect susceptibility to the convulsant effect of theophylline. Rats received caffeine, 40 mg/kg, or solvent twice a day for 7 days as an intravenous injection. On the eighth day, theophylline was infused intravenously until the onset of maximal seizures. At this pharmacologic end point, rats pretreated with caffeine had significantly higher theophylline concentrations in the brain and cerebrospinal fluid than did control (solvent-pretreated) animals. Although the concentration differences were relatively small (approximately 11%), they demonstrate in principle the development of caffeine-induced tolerance to the neurotoxic effect of theophylline. Additional experiments showed that the caffeine effect on theophylline neurotoxicity is not acutely mediated by paraxanthine, a major metabolite of caffeine. PMID- 2304924 TI - Exercise-induced ovarian dysfunction in the rat. AB - The effect of treadmill running on estrous cycles was studied in the rat. Additional effects of cortisol acetate treatment and adrenalectomy were studied in both exercising and sedentary rats. Sedentary rats given the vehicle or cortisol acetate, or which had been adrenalectomized, all exhibited estrous cycles with diestrous phases that were uniformly less than 4 days. However exercising rats had extended estrous cycles; 50-62% of cycles were incomplete within 11 days and 78% of rats had cycles with diestrous phases that were more than 4 days long. There were no difference in duration of estrous cycles of running rats that received vehicle, received cortisol acetate, or had been adrenalectomized. We conclude that the running regimen resulted in a delay of the normal ovulatory period in rats, and that this effect of running was not affected by the presence or absence of glucocorticoids. PMID- 2304926 TI - Elderly people's risk of HIV infection. PMID- 2304925 TI - Excessive sympathetic nervous system activity decreases myocardial contractility. AB - The objective of this study was to determine whether myocardial contractility is depressed by intense activation of the sympathetic nervous system. A massive sympathetic discharge was produced by injecting veratrine or sodium citrate into the cisterna magna of anesthetized rabbits (n = 10). Two and one-half hr later, the hearts were isolated and their left ventricular (LV) performance evaluated and compared with the LV performance of hearts isolated from control animals (n = 10). LV performance was evaluated from steady-state peak isovolumic systolic and end-diastolic pressures that were generated at various end-diastolic volumes (LV function curves). The relationship between peak LV systolic pressure (or the average peak developed LV wall stress) and LV end-diastolic volume was rotated downward (P less than 0.01) in the hearts removed from rabbits treated with veratrine or citrate. The LV end-diastolic pressure or LV end-diastolic wall stress of these hearts was not different from control at any end-diastolic volume. The diminished ability of the experimental hearts to develop systolic pressure or wall stress suggests that intense sympathetic activation depressed contractility. Severely damaged myofibers, located largely in the subendocardium, were found in these hearts. Furthermore, the depressed contractility was not related to pulmonary edema since only 2 of 10 rabbits developed edema. PMID- 2304927 TI - Making resource management work. AB - Following Government pressure for more resource management, nurses at the Radcliffe Infirmary set up a pilot scheme putting the system into action. This, the first of a two-part series, describes how ward sisters assumed responsibility for budgeting their wards. PMID- 2304928 TI - In search of the perfect assessment. AB - Assessment tools are essential in planning individual care for people with learning difficulties, but nurses often lack confidence in using them. This article looks at why this is, and discusses 10 commonly used tools. PMID- 2304929 TI - Oxygen therapy. PMID- 2304930 TI - Quality assurance update--introducing the system. PMID- 2304932 TI - What is psychotherapy? AB - Nurses are increasingly being called on to employ psychotherapeutic skills with their patients and clients. This major new series will examine these skills, which are invaluable in general, as well as psychiatric, settings. PMID- 2304931 TI - Catheters: making an informed choice. AB - Catheters are used in over 10 per cent of hospital patients, but many nurses still have misconceptions about them. This two part series looks at the correct use of catheters and the problems associated with catheterisation. PMID- 2304933 TI - Ensuring safe arrival--the midwife's role in caesarean section. AB - The rate of caesarean births has increased rapidly in the last 20 years. Midwives have a vital role in helping the parents through this experience and ensuring it is as positive as possible. PMID- 2304935 TI - After the festivities ... the diet plan! PMID- 2304936 TI - Molecular endocrinology and steroid hormone action. Proceedings of the Fourth International Symposium on Cellular Endocrinology. Lake Placid, New York, August 24-27, 1988. PMID- 2304934 TI - Eusol--the final word! AB - Despite a wide range of new wound care products, nurses continue to use sodium hypochlorite to treat wounds. This article explores the potential dangers of this practice. PMID- 2304938 TI - Long-term prognostic implications of sex-steroid receptors in human cancer. AB - Progesterone receptor analysis has been used to enhance the prognostic usefulness of estrogen receptor analysis in breast cancer. Immunocytochemical assays for both steroid receptors have been shown to correlate with established biochemical techniques but lack long term clinical follow-up studies to validate their use. One hundred fifty- two patients were followed for up to 10 years after primary surgical treatment. Steroid receptor analyses, using both biochemical and immunocytochemical techniques were performed on their tumor specimens. Patients with estrogen or progesterone receptor positive tumors had longer survival than patients with negative tumors. This difference was most clearly demonstrated with immunocytochemical analysis of estrogen receptors (p = 0.04). The two methods for progesterone receptors gave very similar results. Use of multivariate analysis revealed that ER by immunocytochemical analysis was the only significant predictor of prognosis when all four variables were considered simultaneously (p = 0.04). This study suggests that immunocytochemistry gives comparable results to biochemical analysis for progesterone receptors but that immunocytochemical analysis of estrogen receptors was the stronger single prognostic indicator of the four. PMID- 2304937 TI - Estrogen-induced destabilization and associated degradation intermediates of apolipoprotein II mRNA. PMID- 2304939 TI - Current concepts in endometriosis. Proceedings of the Second International Symposium on Endometriosis. Houston, Texas, May 1-3, 1989. PMID- 2304940 TI - Principles of conventional conservative surgery. PMID- 2304942 TI - The International Narcotics Research Conference (INRC) '89. Ste-Adele, Quebec, Canada, July 9-14, 1989. PMID- 2304941 TI - Fallopian tube and fimbrial function in endometriosis: with a special reference to an ovum capture inhibitor. PMID- 2304943 TI - Autoradiographic localization of [3H]dextromethorphan (DM) in guinea pig brain: allosteric enhancement by ropizine. PMID- 2304944 TI - Prodynorphin messenger RNA expression in the rat anterior pituitary is regulated by estrogen. PMID- 2304945 TI - Morphine increases proenkephalin gene expression in the adrenal medulla by a central mechanism. PMID- 2304946 TI - Pharmacological regulation of striatal prodynorphin peptides. PMID- 2304947 TI - Identification of prodynorphin and proenkephalin mRNA expressing cells in the neurointermediate lobe of the rat pituitary gland. PMID- 2304948 TI - Opioid peptide mRNAs in the rat pineal. PMID- 2304950 TI - The release of alpha-neoendorphin from rat hippocampus following kainic acid induced seizures. PMID- 2304949 TI - Proenkephalin gene expression in cultured chromaffin cells is regulated at the transcriptional level. PMID- 2304951 TI - Is cathepsin B an enkephalin processing enzyme in the tooth pulp? PMID- 2304952 TI - Characteristics of BANA-degrading enzyme in the tooth pulp activated by bradykinin. PMID- 2304953 TI - Blockade of high K+ contractures and Ca(+)+-dependent slow action potentials in frog skeletal muscle by opioid drugs. PMID- 2304954 TI - Effect of chronic administration of morphine and its withdrawal on the rat brain and spinal cord dopamine D1 receptors. PMID- 2304956 TI - Effects of opioids on acetylcholine release into fetal vessels of human perfused placental cotyleda. PMID- 2304955 TI - Effects of iontophoretically applied alpha-casein exorphin on CA1 hippocampal field potentials in vivo. PMID- 2304957 TI - Altered plasma leucine-enkephalin concentrations in patients with established hypertension. PMID- 2304958 TI - Effects of naloxone on pulmonary capillary permeability. PMID- 2304959 TI - Pertussis toxin inhibits morphine-induced release of adenosine from the spinal cord. PMID- 2304960 TI - Penicillins exhibit enkephalinase inhibitory activity in mice. PMID- 2304961 TI - Electrophysiological evidence that tolerance and dependence phenomena are reflected at the ventrobasal (VB) thalamic level in arthritic rats. PMID- 2304962 TI - Immune status of unselected methadone maintained former heroin addicts. PMID- 2304963 TI - Peptides as potential antinociceptive drugs. PMID- 2304964 TI - Effect of panax ginseng extract on the pharmacological actions of morphine in the rat. PMID- 2304965 TI - Neurochemical aspects of morphine tolerance in the freely moving and behaving animal: voltammetric studies. PMID- 2304966 TI - [Regulation of human drugs in the European Common Market]. PMID- 2304968 TI - A single-tube mathematical model of reactive hyperaemia. AB - A mathematical model of reactive hyperaemia is developed using quasi-steady flow in a single tube to represent blood flow in the vascular bed. The role of the myogenic response during reactive hyperaemia is examined by suggesting a linear relationship between tube cross-sectional area S and pressure p, in which S decreases as p increases, thereby modelling the response of the smooth muscle in the blood vessel walls to increases in p which the myogenic mechanism proposes. However, this simple relationship, together with the equations of continuity and Poiseuille flow, lead to an unstable equation for p which is inconsistent with the known boundary conditions. It is necessary to make S a function of p and delta p/delta t in order to achieve a stable response which implies that the myogenic response must be rate sensitive to pressure changes. The resulting equations are then solved for p, S, and flow Q by numerical integration and give results for Q which are in broad agreement with experiment. The model also suggests that the changing pressure gradient governs the flow in reactive hyperaemia rather than changes in the resistance of the blood vessels. PMID- 2304967 TI - Filters and Fourier analysis of gated blood pool studies: a search for the optimal combination. AB - Fourier analysis of gated blood pool studies is performed after filtering the raw data by a spatial median 3 x 3, 9 x 9 or temporo-spatial 9 x 9 x 9 filter. 20 patients and a dynamic cardiac phantom were studied to determine the quantitative effects of these filters and of multiharmonic Fourier filtering (MHFF). The filtered MHFF data, with or without preprocessing, were compared with a 3 D or 2 D filter to the raw data using a chi 2 distribution. The MHFF (two or three harmonics) procedure applied to the raw data of patients without any preprocessing produced the smallest chi 2 value, thus demonstrating the very close relationship between filtered images and raw data. Preprocessing the raw data by the median filter also preserved the signal when two or three harmonics were applied, whereas the 3 D and 2 D (9 x 9) filters did not. The phantom study also demonstrated that MHFF preserved the signal better than any other preprocessing. The median filter introduced a smaller distortion than the 2 D (9 x 9) and 3 D filters. It is concluded that MHFF applied with two or three harmonics on the raw data or after preprocessing by a median (3 x 3) filter is the most successful way of preserving the real signal. It is believed that the other filters should be avoided. The clinical advantage of MHFF processing is to provide both very accurate filtering and parametric images. PMID- 2304969 TI - A special purpose x-ray fan-beam CT scanner for trabecular bone density measurement in the appendicular skeleton. AB - A special purpose x-ray CT scanner with the capability of scanning objects 75-220 mm in diameter with constant relative geometrical resolution has been developed. The data collection scheme for the scanner uses multiple rotations of a linearly shifted, asymmetric fan beam permitting user-defined variable resolution. Details of hardware and the calibration procedures for the scanner are described and the methods used to measure trabecular bone density (TBD) in the peripheral skeleton are outlined. The standard error of estimate (SEE) of a calibration line of pixel value as a function of K2HPO4 concentration was determined to be 0.07%. The short term, in vivo precision of the TBD determination, by repeated measurements of a volunteer with repositioning between each measurement, was +/- 0.67% (coefficient of variation (CV] with a 50s scan time and a radiation dose of less than 20 mR per slice. PMID- 2304970 TI - Volume-selective and spectroscopically resolved NMR investigation of diffusion and relaxation in fertilised hen eggs. AB - A radiofrequency and field-gradient pulse sequence is presented permitting the non-invasive, volume-selective and spectroscopically resolved determination of incoherent transport parameters with the aid of an NMR field-gradient method. With proton NMR, diffusion or (quasi-incoherent) perfusion coefficients as low as 10(-12) m2 s-1 are accessible with gradients G less than or equal to 100 mT m-1 for T2 greater than or equal to 0.3 s. If coherent motions like flow are superimposed, the gradient pulses can be compensated for phase shifts arising from uniform or accelerated motions. The efficiency of the suppression of the influence of coherent motions was demonstrated in test experiments with phantom sample arrangements. As a biophysical application, the local diffusion coefficients D and relaxation times T1 and T2 of hen eggs were studied during the first days of incubation. In the yolk, strongly non-exponential decay curves were observed for the CH2 line. The translational displacements of water were found to be restricted. The relaxation and diffusion parameters turned out to be constant during the incubation. Medical applications of the pulse sequences are discussed. In one case we demonstrate that attempts to assign resonance lines can be checked by the condition that resonances of the same compound must have identical diffusion coefficients. PMID- 2304971 TI - The geometric transfer function for cone and fan beam collimators. AB - Geometric response functions are derived for both cone and fan beam collimators for the scintillation camera. The formulation is based on an effective response function which is determined by the geometric response of a single hole. The technique provides an accurate description of the spatial resolution by characterising the complete geometric response function which includes the effects of the shape and orientation of the collimator holes. The theoretical formulation was used to design a fan beam collimator for SPECT imaging and was shown to agree well with the experimental results. PMID- 2304972 TI - Opto-thermal in vivo monitoring of sunscreens on skin. AB - Opto-thermal transient emission radiometry (OTTER) provides a convenient means for in vivo and in situ monitoring of human or animal skin properties and surface concentrations of topically applied substances, such as drugs and cosmetics. This is illustrated with measurements on the rates of disappearance from skin of a number of commercial sunscreen preparations. The break-up of the physical structure of creams on skin can also be monitored through dynamic phase change phenomena, induced by a laser pulse. PMID- 2304973 TI - Validity of derived measurements of leg-length differences obtained by use of a tape measure. AB - Determining the difference in the length of an individual's legs is often an important component of a musculoskeletal examination. Although measurements are easily obtained with a tape measure, the validity of these measurements is not known. The purpose of this study was to examine the validity of determinations of leg-length differences (LLDs) obtained by use of a specified tape measure method (TMM). Leg-length differences using the TMM and a radiographic technique were determined for 10 subjects who were candidates for clinical leg-length measurements and for 9 healthy control subjects. Validity of the TMM measurements was determined by assessing the degree of agreement between TMM-obtained LLDs and those obtained by the radiographic method. Validity estimates as determined by intraclass correlation coefficients (ICCs) were .770 for patients, .359 for healthy subjects, and .683 for all subjects. When the means of the two values obtained by use of the TMM were compared with the radiographic measurements, the ICCs were .852 for the patient group, .637 for the healthy subjects, and .793 for all subjects. This study suggests that TMM-derived LLD measurements are valid indicators of leg-length inequality and that the estimates of validity are improved by using the average of two determinations rather than a single determination. PMID- 2304974 TI - Effects of mental practice on rate of skill acquisition. AB - The purpose of this study was to investigate the effectiveness of mental practice in increasing the rate of skill acquisition during a novel motor task. Twenty-six subjects were randomly assigned to two groups. The Control Group (n = 13) performed only physical practice; the Experimental Group (n = 13) performed both mental and physical practice. The task was to toss, by flexing the elbow, a Ping Pong ball held in a cup on a forearm splint to a target. The biceps brachii muscle and the long and lateral heads of the triceps brachii muscle were monitored electromyographically to determine any changes occurring during skill acquisition. The Experimental Group's accuracy improved at a significantly greater rate than that of the Control Group. In addition, the Experimental Group demonstrated changes in timing variables that led to a more efficient movement. These changes included a decrease in time from the onset of muscle activity to peak activity and an increase in the time elapsed from the onset of agonist contraction to the onset of antagonist contraction. These results suggest that mental practice may be an important tool in facilitating the acquisition of a new motor skill. PMID- 2304975 TI - Clinical teaching in physical therapy: student and teacher perceptions. AB - Many practicing physical therapists participate in the most crucial phase of a student's education by serving as Clinical Instructors. The purposes of this study were to identify the clinical teaching behaviors perceived as most effective and most hindering by students and CIs and to compare the response rates of students in bachelor's and master's degree programs. A published 58-item questionnaire was completed by 172 participants from eight physical therapy education programs. The results were analyzed by multivariate analysis of variance. The perceived most helpful teaching behaviors pertained to providing information through feedback. The perceived most hindering behaviors were intimidating questioning and correcting student errors in the presence of patients. The different student and CI ratings for the item "leaves student alone until asked to supervise" has important ethical and educational implications. Master's and bachelor's degree students' ratings differed significantly on four teaching behaviors. Different instructional methods might be necessary for educating these students. PMID- 2304976 TI - A review of myotatic reflexes and the development of motor control and gait in infants and children: a special communication. AB - Although the mechanism of the phasic myotatic (or "stretch") reflex is well known, the role of this reflex in adult gait remains speculative. The acquisition and development of locomotor skills with respect to the development of the myotatic reflex require further study in both healthy and neurologically impaired children. In this article, the well-documented properties of the healthy adult's myotatic reflex are compared with recent findings of the myotatic reflex in healthy infants and children and contrasted with reflex properties in patients with cerebral palsy. These data allow us to begin to characterize the emerging features of the stretch reflex in normal and pathological early development. From these data, we can begin to speculate about the relationship between changes in stretch reflexes and the acquisition of skillful movement and gait in early childhood. PMID- 2304977 TI - Valgus stress test study. PMID- 2304978 TI - Photocoagulation of human plasma: acyl serine proteinase photochemistry. AB - Human alpha-thrombin or bovine Factor Xa was acylated at the active site serine hydroxyl with alpha-methyl-2-hydroxy-4-diethylaminocinnamic acid. These modified serine proteinase enzymes showed no plasma coagulation biological activity in the absence of light. Photolysis of the acyl serine proteinase enzymes in plasma for 1-35 s with monochromatic 366 nm light isolated from a high pressure mercury arc results in coagulation of the plasma. For example, photolysis of 3 NIH U of the acyl human alpha-thrombin for 5 s in human plasma results in a clot in 23 s. For comparison, 1 NIH U of unmodified human alpha-thrombin gave a clot in 21 s under the conditions of the assay but without photolysis. Appropriate controls showed that the coagulation is the result of the formation of active thrombin due to photodeacylation of the enzymes. The photoinduced clotting time measured is dependent on acyl thrombin concentration and photolysis time. Thus higher concentrations of acyl thrombin and longer photolysis times give a shorter clotting time. A kinetic scheme based upon Lineweaver-Burke analysis of the clotting process is developed. PMID- 2304979 TI - Scavenging of singlet molecular oxygen by imidazole compounds: high and sustained activities of carboxy terminal histidine dipeptides and exceptional activity of imidazole-4-acetic acid. AB - Singlet molecular oxygen was generated by illumination of phenosafranin in phosphate buffer at pH 7.5. Relative efficiencies of various imidazole compounds to form endoperoxides were assayed by following at 25 degrees C the rate of light and imidazole-dependent bleaching of N,N-dimethyl-4-nitrosoaniline. Of over 30 imidazole compounds tested, imidazole-4-acetic acid, a major catabolite of histamine in mammals, exhibited the highest activity. L-Carnosine (beta-alanyl-L histidine), a natural dipeptide prevalent in striated muscle of mammals, possessed several properties important for a physiologically significant scavenger of singlet oxygen. On a molar basis, this readily water-soluble C terminal histidine dipeptide reacted with singlet oxygen two- to four-fold faster than free L-histidine and approximately two-fold faster than the N-terminal L histidine dipeptides tested. Furthermore scavenging ability of L-carnosine did not appreciably increase or decrease with time of reaction, in contrast to behaviors exhibited by a number of other imidazole compounds that included some other C-terminal L-histidine dipeptides. The fungal metabolite, ergothioneine, blocked singlet oxygen generation by illuminated phenosafranin. PMID- 2304980 TI - Photooxidative damage to lysosomes of cultured macrophages by acridine orange. AB - Cultured cells accumulate acridine orange (AO), which is a weak basic dye and a photosensitizer, in lysosomes and other acidic compartments. During exposure to blue light, AO-loaded macrophages show decreasing red granular fluorescence and increasing green diffuse fluorescence. This is hypothesized to represent peroxidative damage to lysosomal membranes resulting in an impaired proton gradient with deprotonation of the AO to its uncharged form and subsequent leakage of the dye. Further damage to the lysosomal membranes will result in release of lytic enzymes from the lysosomal compartment into the cytosol, leading to degeneration and finally cell death. The survival of AO-loaded and light exposed macrophages is controllable by varying the exposure times to blue light. Inhibition of lysosomal proteases by E-64 results in increased cell survival after AO and blue light-mediated damage, indicating a role of proteolytic enzymes in this type of damage. Morphological analysis shows 'rounding up' with formation of retraction fibrils and pronounced plasma membrane blebbing. The formation of autophagic vacuoles is an early and pronounced event. After protease inhibition, however, all these phenomena are inhibitable to a considerable degree. We have thus directed photooxidative damage selectively to lysosomal membranes and their contents. This technique will allow further detailed studies of the role of lysosomes in degeneration-regeneration processes. PMID- 2304981 TI - Photoreactions of macrocyclic dyes bound to human serum albumin. AB - The photophysical properties of tetrakis(4-sulfonatophenyl)porphyrin (H2TSPP), its tin (IV) complex (SnTSPP), aluminium(III) trisulfonatophthalocyanine (AIPCS), and the corresponding zinc(II) complex (ZnPCS), have been measured in H2O, D2O, and upon binding to human serum albumin (HSA). The triplet excited states of the various macrocyclic dyes generate singlet molecular oxygen, O2(1 delta g) in high quantum yield upon illumination in O2-saturated solution, even in the presence of HSA. The triplet states also abstract an electron from 4-aminophenol, forming the radical anion of the macrocycle. Quenching rate constants and quantum yields have been measured for the various processes in the presence and absence of HSA. It is found that HSA binds all the dyes at nonspecific sites close to the interface in such a manner that the dyes remain accessible to species residing in the solution phase. Dyes that do not possess axial ligands complexed to the central cation (e.g. H2TSPP, ZnPCS) are able to bind also at a deeper, more specific site on the protein where they are protected from species in solution. Under such conditions, triplet quenching by 4-aminophenol is restricted to long-distance electron tunnelling, for which the rate is relatively slow. PMID- 2304982 TI - Induction of Trichoderma sporulation by nanosecond laser pulses: evidence against cryptochrome cycling. AB - An important question in the study of photoreceptor action in morphogenesis is whether the chromophore is unidirectionally photobleached, or whether it is recycled, allowing each receptor molecule to be counted more than once. The common soil fungus Trichoderma harzianum grows vegetatively in the dark and sporulates in response to a pulse of blue or UV-A light. Colonies were grown at 26 degrees C, transferred to 3 degrees C, illuminated with non-saturating light, and then put back at 26 degrees C to sporulate. The fluence-response curves for photoinduction in the cold and at 26 degrees C were identical, indicating that there are no enzymatic transduction processes during irradiation. Regions of the perimeter of dark-grown colonies were given single pulses (maximum duration, 30 ns) at 355 nm with a neodymium laser. We obtained a complete fluence-response curve for the laser pulses, which agreed with data for irradiations in the second to minute range. Photoinduction at 3 degrees C, and validity of Bunsen-Roscoe reciprocity from nanoseconds to minutes, support the hypothesis that the inductive event is a simple first-order photobleaching reaction. PMID- 2304983 TI - Corset platysmaplasty. AB - Contemporary surgery to rejuvenate the aging neck commonly includes some type of platysma modification. Most currently used methods of platysmaplasty involve upper midline plication, muscle resection, or transection. These methods, however, have their shortcomings, often producing necks that display persistent or recurrent paramedian muscle bands, visible submandibular gland bulges, and various contour irregularities. Corset platysmaplasty was developed to avoid these postoperative imperfections. After an adequate subcutaneous and subplatysmal lipectomy has been performed, the two medial edges of the platysma are joined together with a continuous suture that runs down, and up, and down almost the full-height of the neck to create a smooth, flat, multilayered seam, leaving no free muscle edges to return as visible bands. Progressive side-to-side tightening along the midline seam defines the "waistline" of the neck. Additional submandibular suturing is then done to create strong, flat, vertical muscle pleats that correct submandibular gland bulging and refine the jawline and anterolateral neck contours. Corset platysmaplasty is useful for all patients with visible paramedian muscle bands and all patients who would benefit from having a decussated upper neck platysma opened for submuscular defatting, including patients with oblique, palpably firm necks that suggest a vertically short platysma muscle or low-lying hyoid bone. The paper is based on the results with 75 patients having undergone corset platysmaplasty, most having been followed for 1 to 3 years. PMID- 2304984 TI - Surgical correction of Crouzon syndrome. AB - This study analyzes the results of surgical treatment in 39 patients with the Crouzon syndrome. Early fronto-orbital advancement and craniectomy were universally successful in relieving raised intracranial pressure and in reducing ocular proptosis. However, definitive cosmetic correction was not achieved, and early cranial surgery was not able to prevent the development of midface hypoplasia. Thirty-two midfacial advancements have been performed in 30 patients. Sixteen patients had sufficient follow-up data for more than 2 years postoperatively. In all patients, a satisfactory early postoperative result was achieved. In the long-term follow-up group, 11 patients have maintained a satisfactory appearance, while 5 have developed recurrent deformity. Analysis shows this to be associated with a younger age at operation and continued mandibular growth. Frontofacial advancement in adults achieves good long-term results but is associated with a higher incidence of complications. PMID- 2304985 TI - Le Fort fractures without mobility. AB - The Le Fort fracture without maxillary mobility constitutes 9 percent of maxillary fractures observed over a 3-year period. A high Le Fort (level II or III) injury exists as a one- or two-piece incomplete fracture. The degree of fracture is insufficient to permit mobility of the maxillary alveolus. Frequently, an obvious unilateral zygomatic fracture is present. Physical findings consist of bilateral eyelid ecchymosis and malocclusion. The occlusal disturbance may consist of either crossbite, open bite, maxillary rotation, or lack of proper dental intercuspation. On CT scan, fractures are best demonstrated in the posterior and medial maxillary walls at the Le Fort I level; they are most obvious unilaterally with contralateral fractures that may be subtle. Bilateral maxillary sinus fluid is consistently present on CT. Treatment usually consists of observation and traction elastics but may require mobilization of the fragments followed by open reduction and rigid fixation. PMID- 2304986 TI - The functional pectoralis major musculocutaneous island flap in head and neck reconstruction. AB - We describe our experience with the true island pectoralis major musculocutaneous flap in patients with high-volume defects for whom free-tissue transfer is unsuitable. Our operative technique is presented. We have modified the method of making a true island of the pectoralis major musculocutaneous flap on a muscle free pedicle as first described by Wei et al. in 1984. This maintains maximal donor-site muscle function and facilitates closure of the donor-site defect. We present our results in 24 patients, in whom the flap has proved to be robust and reliable. The flap's advantages in terms of increased pedicle length, wider arc of rotation, decreased pedicle bulk, and improved cosmesis of the reconstruction are discussed. PMID- 2304987 TI - Augmentation mammaplasty: a comparative analysis. AB - With the continuation of augmentation mammaplasty as a desirable operation for a large segment of the female population in the United States, the problem of fibrous capsular contracture that has been present since the inception of the operation has persisted. Various approaches to the problem have been entertained, and a lessening of the incidence has occurred as reviewed in our earlier report, which follows augmentation mammaplasty in our clinic from 1962 through 1979. In this retrospective study, no significant difference in contracture rate was seen based on patient smoking habits, operative approach used, or implant type. It is important to note that the total experience with the low-bleed implant was significantly lower in terms of number of patients meeting the criteria of this retrospective study than the standard gel mammary implant. Greater follow-up time and number of patients will be evaluated in future retrospective studies. We have demonstrated in this study that placement of the implant beneath the pectoral muscle has significantly diminished the incidence of capsular contracture both as Baker grades II, III, and IV and as Baker grades III and IV. The retropectoral site has become the preferred location for the prosthesis in our clinic. There is no appreciable alteration in the overall shape of the breasts from this approach, and therefore, it will continue to be the preferred method. Rates of incidence of hematoma, the most frequent adverse reaction after contracture, were not significantly different between the retropectoral and retromammary implant sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2304988 TI - Capsular contracture after breast reconstruction with silicone-gel and saline filled implants: a 6-year follow-up. AB - A major problem after breast reconstruction with augmentation mammaplasty is contracture of the fibrous capsule around the prosthesis. In a series of 72 breasts in 65 women, silicone-gel and saline-filled implants were randomly selected prior to breast reconstruction. The results were judged with respect to consistency, tenderness, wrinkles, and sounds by two independent plastic surgeons according to the breast augmentation classification (BAC) and by the patients themselves. Capsular contracture was found by the surgeons in 50 percent of the gel implant group and in 16 percent of the saline implant group, which is in conformity with the results of the follow-up 5 years earlier. The incidence of deflation was 16 percent in the saline group and occurred in different sizes of both overinflated and underinflated prostheses. The degree of slow leakage from saline implants will be discussed. Despite the high rate of contractures in the gel group, 85 percent of all patients were satisfied with the result of the reconstruction. PMID- 2304989 TI - Comparative study of survival of autologous adipose tissue taken and transplanted by different techniques. AB - In recent years, adipocytes obtained by suction-assisted lipectomy have been used for implantation by injection methods. This study is designed to assess the appearance of suctioned and excised adipose tissue and its survival after being injected or implanted into different tissues (0.5 cc into the rectus muscle and 0.5 cc into the dorsal ear skin) of New Zealand White rabbits. The results showed that significant numbers of adipocytes were ruptured after suction procedures. The intact cells represented approximately 10 percent of the fat cell population. Fat cells in aspirated and excised samples remained intact and did not differ histologically. After being injected into tissue, adipocytes appeared to survive better for a short term in a more vascularized bed (rectus muscle) than in a low vascular area (ear dermis). Long-term studies at 6- to 9-month intervals revealed transplanted adipose tissue, taken by suction or excision, being replaced with fibrosis, although cystic spaces and only a small number of surviving adipocytes were still present. Insulin did not show any protective effects on survival of the adipocytes during their transplantation. PMID- 2304991 TI - Microvascular angioscopy. AB - The desire for immediate assessment of endovascular pathology in hand and microvascular surgery has led to an investigation of the microvascular angioscope. This study evaluated three angioscopes of differing sizes and specifications to determine their ability to detect intimal lesions such as tears, crush injury, and surface clots. Studies were done in 80 Sprague-Dawley rats and in cadaveric hands. Angioscopic findings were correlated with gross and histologic inspection and found to be 100 percent accurate. We conclude that microvascular angioscopy can provide important information concerning the integrity of vessels less than 1 mm in diameter with excellent optical resolution and with minimal time expenditure. PMID- 2304990 TI - "Sensible" flap coverage of pressure sores in patients with meningomyelocele. AB - Restoration of sensibility in the paraplegic patient is the optimal therapy for the management and prevention of debilitating pressure sores. In patients with an absence of sensibility below the L3 spinal level, a locally transposed arterialized neuromyocutaneous gracilis flap may be uniquely utilized for ischial restoration of sensibility. Two patients with meningomyelocele-induced ischial pressure sores underwent local innervated neuromyocutaneous gracilis flap transposition to insensate areas from below the anatomic level of recipient insensibility. A 10-year follow-up revealed maintenance of sensibility in the flap and spread of sensibility to adjacent insensate areas with no evidence of pressure sore recurrence. Cadaver dissection and clinical Xylocaine injection demonstrated that the cutaneous sensory innervation to this flap is by means of a consistent sensory branch from the deep neurovascular pedicle, which coincides with the L1-L3 dermatome. PMID- 2304992 TI - Expanding the horizons in treatment of severe peripheral vascular disease using microsurgical techniques. AB - The use of microvascular tissue transfer as an adjunct to arterial reconstruction has begun to have a positive impact on limb salvage in patients with advanced arteriosclerosis and nonhealing ischemic wounds. However, many patients with severe peripheral vascular insufficiency not amenable to conventional arterial reconstructive procedures eventually require limb amputation. We have treated 12 patients with advanced peripheral vascular disease and nonhealing ischemic wounds by three different methods. These included distal bypass alone, distal bypass done in conjunction with free-tissue transfer, and free-tissue transfer alone. All bypass grafts were done to vessels at or below the ankle using a reversed saphenous vein. In each case, the distal anastomosis was performed, using the operating microscope and standard microvascular technique. Mean follow-up for these patients is 18 months. Distal bypass alone resulted in limb salvage in three of five patients. In the combined bypass and free-flap group, three of five patients had salvage of their threatened extremity at a 1-year follow-up. Two patients with ischemic ulcers, rest pain, and unsuitable distal vessels for bypass were treated with free-tissue transfer alone. This resulted in healed wounds, limb salvage, and complete resolution of the rest pain symptoms in both patients. When advanced ischemia is complicated by large areas of tissue loss, combined bypass and microvascular free-issue transfer, performed in stages or simultaneously, is safe and can often result in limb salvage. In the rare instance of a completely obliterated distal runoff bed, free-tissue transfer alone may provide not only a healed wound, but also a means of "indirect" revascularization of the extremity and limb salvage. PMID- 2304993 TI - Replantation of amputated segments after prolonged ischemia. PMID- 2304994 TI - "Mrs.--, how can I help myself?". PMID- 2304995 TI - Microvascular transplantation of expanded free scalp flaps between identical twins. AB - Long-term follow-up of a previous free scalp transplant between identical twins is provided. A recent third transplant between these twins is presented in which donor flap expansion is used prior to transplantation, and the postoperative use of medicinal leeches is discussed. PMID- 2304996 TI - Subcutaneous pseudobursa secondary to suction and surgery. AB - Suction lipectomy has been used throughout the regions of the body to remove vast amounts of subcutaneous fat. The blunt technique allows for a multiplicity of small (4 to 6 mm) channels to be created and the fat removed by suction with little disturbance of the overlying skin, the supporting septa, vessels, or nerves. Abdominolipectomy has been successfully performed for decades, in which large amounts of skin and subcutaneous fat are removed by sharp dissection. The undermining involved in an adbominolipectomy extending from the xiphoid to pubis and laterally to the level of the iliac crest and then supplemented by the suction technique has led to the formation, in some cases, of chronic seromas not relieved by multiple aspirations. Healing and contractions of these seromas causes a deformity of the overlying skin, because it is puckered and drawn upon itself. This results in the formation of a subcutaneous pseudobursa lined by collagen sheets but no epithelial cells. We present 9 patients who have demonstrated this phenomenon. We suggest that in the largest resections, safety is best served by waiting a period of at least 6 weeks between suction and subsequent resection. PMID- 2304997 TI - The elastic flap for lip repair. AB - These cases illustrate a new concept in lip repair. This approach recognizes the great inherent elasticity of the oral cavity and takes advantage of the florid blood supply of the region. Recent laboratory studies of Taylor et al., as well as the works of Manchot and Salmon, are combined with anthropologic observations of tribal customs to formulate another way of looking at lip reconstruction. Triangularization of surgical defects, lip switching, and mobilization of distant flaps are avoided by taking advantage of stretched local tissues. Preoperative expansion is discussed as a future option. PMID- 2304998 TI - Bilateral vermilion flaps for lower lip repair. AB - A more natural reconstructive procedure of the lower lip using bilateral vermilion flaps was applied in five patients with excellent results. The vermilion defects were about two-fifths to three-fifths. In three patients, the vermilion defect was repaired using bilateral vermilion flaps alone. In the remaining two patients, a narrow horizontal lip defect was repaired by bilateral vermilion flaps and a subcutaneous V-Y advancement flap of the lower lip. A single vermilion flap or bilateral vermilion flaps are considered to be of great value for vermilion reconstruction because of the inherent elasticity and common anatomic unit. The postoperative scars are not remarkable at all. A long and narrow horizontal lip defect (perhaps within 1.5 cm downward from the vermilion border) may be effectively repaired by the combination of vermilion flap(s) and a V-Y advancement flap without sacrificing any additional healthy tissue. PMID- 2304999 TI - Coverage of bilateral lower extremity calcaneal fractures with osteomyelitis using a single split free gracilis muscle transfer. AB - A case is presented in which a single gracilis muscle was split and used for free tissue coverage of two sites in a patient with bilateral calcaneal fractures and posttraumatic osteomyelitis. Muscle-flap coverage of osteomyelitis and the use of the gracilis muscle for free-tissue transfer are discussed. PMID- 2305000 TI - Intrauterine repair of cleft lip: what's involved. PMID- 2305001 TI - Internal fixation of malar fractures. PMID- 2305002 TI - The future of psychoanalysis. PMID- 2305003 TI - Analysis of a woman's homosexual strivings by a male analyst. AB - Clinical material is presented describing how analysis of the homosexual aspects of a woman patient's transference to a male analyst unfolded. Comparison and contrast is made to previous case reports and discussions of the impact of the analyst's actual gender on analytic work. PMID- 2305004 TI - A taste aversion model of drug discrimination learning: training drug and condition influence rate of learning, sensitivity and drug specificity. AB - A model of drug discrimination based on a lithium chloride (LiCl) flavour aversion was described and examined. Mildly thirsty rats were presented daily with 4 ml of a distinctly flavoured solution which was followed on 50% of the days by an IP injection of LiCl. Prior to the flavour presentation, the rats were injection SC with saline or a training drug (0.04 mg/kg fentanyl or 20 mg/kg pentobarbital) to signal whether LiCl would follow. Almost all rats eventually exhibited stable behaviour that involved drinking most or all of the fluid when it was not to be followed by LiCl and little or no drinking when it was. Such discrimination occurred regardless of whether drug predicted LiCl (learned discomfort) or predicted no LiCl (learned-safety). However, with fentanyl there were clear differences between rats trained with drug under learned-safety and under learned-discomfort conditions for 1) the rate of acquisition of stable performance as a function of LiCl dose, 2) generalization of the training dose to a test dose that was lower, and 3) elicitation of fentanyl responses by pentobarbital. These findings, together with indications that such effects did not always occur with pentobarbital as the training drug, were discussed from theoretical and practical perspectives. PMID- 2305006 TI - Increased serotonin 5-HT2 receptor binding on blood platelets of suicidal men. AB - In search of a physiological marker of depression and suicidal behavior, serotonin receptors of the 5-HT2 type were studied on platelet membranes from 19 control and 22 suicidal subjects. All were young, drug- and medication free men (18-21-years-old). 5-HT2 receptor binding was assayed using tritiated ketanserin at two concentrations. Receptor binding in the suicidal subjects was significantly higher than controls at both concentrations, the mean difference being around 50%. A similar difference between patients with major depressive disorder and matched controls has been observed previously. These findings support the use of 5-HT2 receptors on platelets as a research and diagnostic tool in depression and suicide. PMID- 2305005 TI - Paternal alcohol exposure: paradoxical effect in mice and rats. AB - Male mice consumed liquid alcohol diets containing 25%, 10% or 0% ethanol-derived calories (EDC). Animals receiving the 10 and 0% EDC diets were pair fed to those consuming the 25% EDC diet. After 7 or 14 weeks of consumption, males were bred to non-treated females. Offspring were tested for swimming behavior at 75 days of age. Offspring sired by alcohol-consuming males were more immobile regardless of duration of paternal alcohol consumption or housing conditions (group or isolated). Imipramine (5, 15 mg/kg) reversed this effect such that after drug treatment, alcohol-sired offspring were less immobile than controls. Propranolol (1, 3 mg/kg) eliminated the group differences. Yohimbine (1, 10 mg/kg) significantly increased immobility in all groups but did not reverse the effects of paternal alcohol consumption. Metergoline (1 mg/kg) increased immobility in all groups but did not reverse the effects of paternal alcohol exposure. When rat offspring of alcohol-consuming fathers were tested, their swimming behavior was opposite to that of mice (i.e., rats were less immobile). However, as observed in mice, the effect was reversed by imipramine. These results extend the evidence for paternally mediated behavioral mutagenesis. They also indicate that the direction of induced changes are species dependent and that some of these effects, regardless of direction of change, are mediated by neurochemical changes sensitive to imipramine. PMID- 2305008 TI - Naloxone enhances the expression of morphine-induced conditioned place preference. AB - The present study examined the effects of naloxone on acquisition and expression of morphine-induced conditioned place preference (CPP). Three groups of rats were given morphine (5 mg/kg, SC), both morphine and naloxone (1 mg/kg, SC), or saline paired with a distinctive environment. On alternating days they were given saline paired with another distinctive environment. After four exposures to each environment, the animals were given a preference test in which they had access to both environments simultaneously while under the influence of either naloxone (1 mg/kg, SC) or saline. Morphine-conditioned animals showed CPP evident as an increased amount of time spent in the drug-associated environment relative to saline controls. Rats given both naloxone and morphine during conditioning, and saline on the test day, did not show CPP. In contrast, morphine-conditioned animals given naloxone on the test day showed stronger CPP than morphine conditioned animals given saline. These findings indicate that naloxone blocks the acquisition, but enhances the expression of morphine-induced CPP. In a separate experiment, the effects of naloxone on locomotor activity were determined during the CPP test. The results indicated that naloxone decreased locomotor activity. In morphine-conditioned animals only, naloxone also produced an increase in the amount of time per entry in the drug-associated environment. The results suggest that naloxone may enhance morphine-induced CPP by decreasing locomotor activity that may otherwise compete with expression of CPP. PMID- 2305007 TI - Effects of acute administration of diazepam and d-amphetamine on aggressive and escape responding of normal male subjects. AB - Normal males participated in sessions providing two operant response options and were administered either diazepam (study I and II) or d-amphetamine (study II). The acute effects of diazepam on human aggressive responding, which ostensibly subtracted points from another person, were determined in study I. Study II was conducted to determine the extent to which social context and response consequence influenced diazepam (study I) and d-amphetamine (previous research) effects on aggressive responding. In study II, the other response option was escape responding which protected the subject's counter from point losses. Aggressive and escape responding were engendered by subtracting points from the subject's counter, and maintained by initiation of intervals free of point loss. Point subtractions were attributed to the other person (study I) or to a machine (study II). Responding to accumulate points exchangeable for money was available in both studies. Acute diazepam administration decreased aggressive responding in most subjects (study I), slightly increased escape responding (study II), and decreased responding to accumulate points. In study II, d-amphetamine increased both escape responding and responding to accumulate points. The effects of d amphetamine and diazepam were altered by the instructed source of point loss. PMID- 2305009 TI - Sleep laboratory investigations on hypnotic properties of melatonin. AB - Melatonin (MLT), a pineal hormone, has some sedative and hypnotic properties. To explore this effect further 20 young, healthy volunteers exposed to artificial insomnia participated in a double-blind, placebo controlled, parallel group design study. They slept in a sleep laboratory for several consecutive nights and were polygraphically monitored and subjected to a battery of psychometric tests and standardized self-report questionnaires each morning. One night all subjects received only placebo (21:00 hours) and on a second night half of them were subjected to placebo and half to MLT. On the later night blood MLT levels were measured. Polygraphic recordings revealed that MLT at bedtime decreased the time the subjects were awake before sleep onset (P less than 0.025), sleep latency (P less than 0.05), and the number of awakenings during the total sleep period (P less than 0.025), and increased sleep efficiency (P less than 0.05). In addition, it decreased sleep stage 1 (P less than 0.05) and increased sleep stage 2 (P less than 0.025). On the morning following the treatment most objective and subjective measures for awakening quality showed a trend towards improvement after MLT. One hour after its oral administration, serum MLT rose to a high pharmacological level (25817 pg/ml; median), but individual peak serum MLT levels varied by a factor of 300.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305010 TI - Effects of acute or chronic carbamazepine on experimentally-induced conflict in the rat. AB - The effects of acutely or chronically administered carbamazepine were studied in rats submitted to the modified Geller-Seifter conflict test. Diazepam was used as a standard anxiolytic. The results showed an increase in punished response after carbamazepine, as observed with diazepam, leading to the suggestion of an anti conflict-effect for this drug. No tolerance to the anti-punishment-effect was seen after chronic carbamazepine administration. PMID- 2305011 TI - Effect of diazepam on behaviour and associated changes in ascorbate concentration in rat brain areas: striatum, n. accumbens and hippocampus. AB - The effect of diazepam on spontaneous and tail-pinch-induced behaviour was monitored together with the measurement of extracellular ascorbate using constant potential voltammetry with carbon paste electrodes. Diazepam (3 mg/kg) was followed by eating during the 1st hour after administration in non-food-deprived rats and a reduction in the behaviour triggered by a mild tail-pinch 90 min after drug administration. There was no change in ascorbate concentration in parallel with the spontaneous eating; however, the brisk increase in ascorbate concentration in striatum, nucleus accumbens and hippocampus, which accompanies the tail-pinch, was decreased in size and duration after diazepam. This effect was blocked by the central benzodiazepine receptor antagonist Ro15 1788 (5 mg/kg). PMID- 2305012 TI - Changes in seizure threshold and aggression during chronic treatment with three anticonvulsants and on drug withdrawal. AB - Sodium phenobarbitone (20 and 70 mg/kg) had a significant anticonvulsant action against pentylenetetrazole-induced seizures, which persisted for 21 days of treatment. On drug withdrawal there was a significant decrease in seizure threshold below control level 24-48 h after the last dose of 70 mg/kg. Phenytoin (40 mg/kg) had a significant anticonvulsant action after 7 days of treatment and this persisted for 21 days of treatment. On drug withdrawal there was a significant decrease in seizure threshold 48 h after the last dose. Lorazepam (0.1 mg/kg) had a significant anticonvulsant action, but the group tested after 21 days of treatment did not differ from the controls, indicating that tolerance had developed to this effect; on drug withdrawal there was a decrease in seizure threshold from 24 to 72 h. The only drug to increase aggressive behaviour was sodium phenobarbitone (70 mg/kg); this reached significance after 14 and 21 days of treatment and occurred 8 h after drug administration; 0.5 h after drug administration phenobarbitone (70 mg/kg) abolished aggressive behaviour. After 7 days of treatment phenobarbitone (70 mg/kg) increased social behaviour 0.5 h after administration and this was still increased after 21 days of treatment. On drug withdrawal, there were no changes in aggressive behaviour, but there were significant decreases in social behaviour 24 and 48 h after phenobarbitone (70 mg/kg) withdrawal and 24, 48 and 72 h after lorazepam (0.1 mg/kg) withdrawal. PMID- 2305013 TI - Scopolamine effects on memory, language, visuospatial praxis and psychomotor speed. AB - Scopolamine hydrobromide was administered by subcutaneous injection to 30 young subjects in a dose of 0.22 mg/70 kg, 0.43 mg/70 kg, or 0.65 mg/70 kg. Treatment effects were compared to placebo on an extensive cognitive assessment battery. Almost all tests in the battery had been previously administered to Alzheimer's disease patients and nondemented elderly subjects. Scopolamine produced deficits on tests of verbal recall, visuospatial recall, visual recognition memory, visuospatial praxis, visuoperceptual function, and psychomotor speed. Immediate memory, language function, object sorting, and frequency of intrusion errors were unaffected. The low dose of scopolamine produced some peripheral anticholinergic signs but did not affect the cognitive measures. The results support the conclusion reached in previous studies that the cognitive profile of scopolamine injected young subjects is more similar to that of the nondemented elderly than to that of Alzheimer's disease patients. PMID- 2305014 TI - Nicotine conditions place preferences after intracerebral administration in rats. AB - A single-trial place conditioning procedure, one treatment and one non-treatment during two daily conditioning sessions followed by a single test session on the 3rd day, was used to examine the place conditioning effects of intracerebrally administered nicotine. In the first series of experiments, Sprague-Dawley male rats were implanted unilaterally with guide cannulas aimed at the lateral ventricle. After 1 week, rats received either "treatment" (nicotine in 2 microliters phosphate buffer or 2 microliters of buffer alone) or "no treatment" (no injections) before being placed in the black or white compartment of a three compartment place-conditioning apparatus for 20 min. The next day the rats received the opposite treatment before being conditioned in the opposite compartment. On day 3, animals had free access to the entire apparatus for 15 min and the time spent in each compartment was recorded automatically. Even though the rats exhibited a baseline bias for the black compartment, intracerebroventricular nicotine induced positive place preferences relative to buffer control, i.e. if treatments were paired with the black compartment, nicotine enhanced the preference for the black compartment, and if the treatments were paired with the white compartment, nicotine induced a preference for the white compartment. In addition, the nicotine-induced preference response was antagonized by the co-intraventricular administration of mecamylamine. In a second series of experiments, animals were implanted unilaterally with guide cannulas aimed at the pendunculopontine tegmental nucleus of the mesopontine tegmentum. Nicotine microinjection, 1.2-18.5 nmol in 0.5 microliter buffer, induced a dose-dependent positive place preference response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305015 TI - Repeated exposure to diisopropylfluorophosphate (DFP) produces increased sensitivity to cholinergic antagonists in discrimination retention and reversal. AB - This experiment examined the effects of repeated exposure to diisopropylfluorophosphate (DFP), an organophosphate anticholinesterase, on the retention and reversal of a visual discrimination and on the number of muscarinic receptors in the brain. Rats were trained in a serial reversal procedure. After achieving stable performance, the rats were divided into two groups. One group received repeated injections of DFP, the other group received injections. To determine whether DFP-treated rats would be more sensitive than normal rats to stresses on the cholinergic system, each rat was injected with saline or one of three doses of scopolamine, a muscarinic receptor blocker, prior to testing on every 6th day. DFP alone caused no impairment in performance. Scopolamine produced a greater impairment in DFP-treated rats than in control rats. Similar results were obtained in a second behavioral task, match-to-sample in a water maze, using the same DFP treatment protocol and only one dose of scopolamine. The number of muscarinic receptors and acetylcholinesterase activity levels were reduced on the 2nd and 15th day after the end of DFP treatment. These results demonstrate that although repeated exposure to organophosphate anticholinesterases may not alter discrimination behavior directly, it may compromise the central nervous system so that it cannot react normally when challenged. PMID- 2305016 TI - Bromocriptine induces climbing behaviour: possible D-1 or D-2 dopamine receptor involvement. AB - The ability of bromocriptine (BRC), a dopamine D-2 receptor agonist, to induce climbing behaviour was studied in mice. BRC (2-32 mg/kg IP) evoked climbing behaviour. The maximum effect was obtained with 8 mg/kg, while higher doses of BRC (16 and 32 mg/kg) were less effective. Climbing began about 2 h after injection and was most marked 5 h after bromocriptine administration. Pretreatment of animals with the dopamine antagonist pimozide (0.5 mg/kg IP) decreased BRC-induced climbing. Sulpiride (0.25-1.25 mg/kg IP), a potent D-2 antagonist and/or SCH 23390 (0.025 and 0.05 mg/kg SC), a D-1 receptor antagonist, also decreased the response. Furthermore, the climbing behaviour induced by BRC was abolished by pretreatment with reserpine plus alpha-methyl-p-tyrosine (AMPT). Concomitant administration of apomorphine (APO) and BRC potentiated the effect of APO on climbing. Concomitant injection of BRC and SKF 38393 (SKF, D-1 agonist) reduced the effect of SKF on climbing, while administration of BRC 4 h before SKF potentiated the effect of both drugs. It is suggested that BRC induces climbing through D-1 and/or D-2 dopamine receptors. PMID- 2305017 TI - Metergoline abolishes the prolactin response to buspirone. AB - Pretreatment of nine healthy subjects with the non-selective 5-HT receptor antagonist, metergoline (4 mg), abolished the increase in plasma prolactin produced by the anxiolytic drug, buspirone (15 mg). While these findings are consistent with a role for 5-HT receptors in the stimulatory effect of buspirone on plasma prolactin, a dopaminergic mechanism cannot be excluded by the present data. PMID- 2305018 TI - Psychological and physiological assessments on American hostages freed from captivity in Iran. AB - Medical evaluations of 52 Americans held hostage in Iran for 444 days included psychological testing and physiological measurements. Psychological testing utilized the Minnesota Multiphasic Personality Inventory (MMPI) and the 16 Personality Factor Questionnaire (16-PF) and focused on the stress management capabilities of the group upon their arrival at Wiesbaden, West Germany. Physiological testing utilized plasma and urinary cortisol along with plasma and urinary catecholamine levels to help document former hostages' stress responses following their release from captivity. Saliva cortisol and testosterone were measured over the first three hospital days to assess the group's psychophysiological recovery. Psychological testing indicated that the former hostages, as a group, were generally well defended, appearing to have endured their ordeal well. In contrast, plasma and saliva cortisol, urinary catecholamines, and saliva testosterone were seen to be highly elevated. These physiological measures appeared to reflect three strong affects: distress, anxiety, and elation. Saliva cortisol was the only physiological measurement that demonstrated a significant correlation with psychiatrists' ratings of the released hostages' psychological disturbance. Psychiatrists' disturbance ratings appeared to be a valid psychometric estimate, as adduced from their correlations with MMPI and 16-PF major scales. PMID- 2305019 TI - Effects of hypnotic, placebo, and salicylic acid treatments on wart regression. AB - Subjects with warts on their hands and/or feet were randomly assigned to a hypnotic suggestion, topical salicylic acid, placebo, or no treatment control condition. Subjects in the three treated groups developed equivalent expectations of treatment success. Nevertheless, at the six-week follow-up interval only the hypnotic subjects had lost significantly more warts than the no treatment controls. Theoretical implications are discussed. PMID- 2305020 TI - Heart rate reactivity as a predictor of neuroendocrine responses to aversive and appetitive challenges. AB - The present paper examines the neuroendocrine influences of aversive and reward incentives (noise and shock versus monetary bonuses) presented during reaction time tasks administered to 71 healthy men (ages 21 to 35) classified as being high (N = 30) or low (N = 41) in heart rate reactivity. High heart rate reactivity was defined as a peak heart rate increase or greater than 19 bpm to a cold pressor test administered on a different day. Independent groups of subjects worked on one of two visual reaction time tasks: either to avoid exposure to noise (115-dBA bursts) and shock (3.5 mV, 2 sec), or to earn monetary bonuses ($0.50). High heart rate reactors showed significant plasma norepinephrine rises from baseline both to aversive incentives and to reward, although they showed significant cortisol responses only during aversive incentives. In contrast, the low heart rate reactors were unresponsive in cortisol and norepinephrine during either type of incentive. These results support psychoendocrine models which view the norepinephrine response as being nonspecifically related to expenditure of effort regardless of the emotional connotations of the challenge, while cortisol is seen as being secreted primarily during periods of distress. The present data further suggest that cardiovascular reactivity is linked to neuroendocrine reactivity, possibly within the central nervous system. PMID- 2305021 TI - Cardiovascular response patterns and speech: a study of air traffic controllers. AB - The present study examined the relationship between cardiovascular (CVS) response and speech among air traffic controllers (ATCs). During two one-hour work sessions continuous EKG, ear pulse, and audio recordings were obtained individually from 24 male ATCs. In one session the controller actively controlled aircraft, while in the other he worked in a support/coordinator position. Session time in both conditions was partitioned on the basis of audio recordings into four mutually exclusive activities: Radio/Phone Talk, Radio/Phone Listening, Casual Talk, and Silence. Change in cardiovascular response pattern as a function of these activities, as well as the influence of a series of moderator variables on cardiovascular response, was assessed by examining heart rate (HR) and the EKG R-wave to ear pulse interval (RPI) relative to a pre-session baseline. The RPI index was employed as a means of unobtrusively tracking blood pressure on a beat by-beat basis. Although reliable, the overall changes in CVS response were modest. Speech-associated reactivity was expressed exclusively by the RPI index. HR changes were not evident in response to speech, rather, the HR index appeared to be most sensitive to situational demand. Discrepancies between the present pattern and magnitude of speech-associated CVS response and those reported previously are discussed in terms of the nature of speech in laboratory versus field settings and measurement methodologies. PMID- 2305022 TI - Social support reduces cardiovascular reactivity to psychological challenge: a laboratory model. AB - In this study we investigated the effects of nonevaluative social interaction on the cardiovascular response to psychological challenge. Thirty-nine college-age females appeared accompanied ("Friend" condition) or unaccompanied ("Alone" condition) to an experimental laboratory. In the Friend condition, partners were present while the subject participated in two laboratory tasks, and the partners' evaluation potential was minimized by design. Subjects in the Friend condition showed reduced heart rate reactivity to both tasks, relative to the Alone group, an attenuated task-related systolic blood pressure response to one of the tasks, and a reduced diastolic blood pressure increase during a solitary interview. In two other instances, partner-related response reductions were apparent only for Type A subjects. None of these effects was accompanied by differences in task performance or self-reported emotional response. Interpersonal support may reduce cardiovascular responsivity to stress, an effect with possible implications for understanding the association between social relationships and cardiovascular risk. PMID- 2305023 TI - Type A behavior, social support, and coronary risk: interaction and significance for mortality in cardiac patients. AB - The 10-year prognostic significance of psychosocial as well as medical risk factors was examined in 150 middle-aged Swedish men. Type A behavior was assessed by means of the Structured Interview; work demand, social support, and other psychosocial factors were registered through standardized questionnaires. The clinical investigation included a standard physical examination, a frontal and sagittal chest x-ray, fasting serum lipids, glucose, and urate, and a 24-hour ambulatory ECG monitoring. Thirty-seven men died during follow-up. Mortality was similar in men with Type A (24%) and Type B (22%) behavior. In multivariate analyses, lack of social support/social isolation was an independent mortality predictor in Type A, but not in Type B men. In both groups, a high frequency of ventricular ectopic beats on 24-hour ECG monitoring and a poor self-rated general health predicted mortality over the 10-year period. The 10-year mortality experience of socially isolated Type A men was 69% and that of socially integrated Type A men was 17% (p less than 0.05). The findings offer a possible explanation for the observed inconsistencies between intervention and follow-up studies of Type A behavior and coronary heart disease. It is suggested that an important effect of Type A modification programs is to increase the availability of social support. This could be the mechanism through which Type A modification exerts its main effects on cardiovascular health. PMID- 2305024 TI - Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients. AB - This report is concerned with the prediction of natural killer (NK) cell activity in 61 Stage I and II breast cancer patients, between the ages of 25 and 70, who were accrued to this project. All baseline interview and testing data were obtained either just before patients were discharged from the hospital, or at their first outpatient visit, within two weeks of discharge. A major interest of this project is the predictive value of perceived social support, as a potential "stress" buffer, related to NK activity. In the main model reported here, we found that a significant amount of NK activity variance could be explained by five variables. Higher NK activity could be predicted by the perception of high quality emotional support from a spouse or intimate other, perceived social support from the patient's physician, estrogen receptor-negative tumor status, having an excisional biopsy as surgical treatment, and actively seeking social support as a major coping strategy (R2 = 0.33, F(5,55) = 5.5, p less than 0.0004). Findings are discussed in terms of host interaction with tumor endocrine status, and the role that social support might play in modulating such activity. PMID- 2305025 TI - Relationship between premenstrual symptoms and oral contraceptive use: a controlled study. AB - Patterns of menstrual cycle-related change were compared in three groups of women differing in their use of oral contraceptives and being matched for age, occupation, and parity. These groups were: a "monophasic group" (n = 35) established on low dose "combined" pills with stable levels of estrogen and progestagen. a "triphasic group" (n = 30) on low dose pills with escalating progestagen dosage, and a "non-pill control group" (n = 57) using nonsteroidal contraceptives. Each woman kept visual analogue ratings of mood, irritability, energy, tension, breast tenderness, bloating, and sexual interest for two or three cycles. Cyclicity was evident in all variables assessed, but the only variable to show a clear difference between groups was breast tenderness; the "monophasic group" showed less premenstrual breast tenderness than the other two groups. The monophasic group also showed a tendency to menstrual rather than premenstrual symptoms. In view of the similarity of timing of most cyclical symptoms in the three groups, it is difficult to attribute such cyclical phenomena to the effects of either ovulation or variation in corpus luteum function. For most subjects, the cyclical changes were relatively mild, and these findings need to be replicated in women suffering from severe premenstrual syndrome. However, alternative explanations need to account for changes in women both taking and not taking oral contraceptives. PMID- 2305026 TI - Changes in plasma lipids and dietary intake accompanying shifts in perceived workload and stress. AB - Plasma lipids, dietary intake, and self-reported stress and workload were assessed in 14 employees twice before major work deadlines (high workload), and once during a comparatively quiescent period of work (low workload). Increases in self-reported stress and workload between the high and low workload periods were significantly positively associated with increases in plasma total cholesterol, although lipid levels were not increased in the group as a whole during the high workload periods. Dietary intake of calories, total fat, and percentage of calories from fat were significantly higher during high workload during a period of high workload is associated with elevated total cholesterol and that dietary intake of foods which raise cholesterol levels is also increased. Further studies of larger groups of subjects may be required to show a frank increase in cholesterol with increased workload. PMID- 2305027 TI - Changes in nucleoid viscosity following X-irradiation of rat thymic and splenic cells in vitro. AB - Unscheduled DNA synthesis (UDS) suggested a higher DNA repair capacity of X irradiated rat thymic (T) cells when compared to splenic (S) cells (Tempel 1980). In the present investigations, damage and repair of DNA supercoiling was measured in T- and S-cells following X-irradiation in vitro by using the nucleoid sedimentation technique and a simplified low-shearing viscometric test. - X irradiation resulted in a dose (0.6-19.2 Gy) - dependent reduction in sedimentation and viscosity of nucleoids. Within a post-irradiation period of 30 45 min after a challenge dose of 19.2 Gy, DNA repair was accompanied by an increase in nucleoid sedimentation and viscosity in T-cells by about 60 and 300, in S-cells by almost 40 and 100%, resp. The increase in nucleoid viscosity within a 30 min repair period could be reduced in a concentration-dependent manner by DNA polymerase - inhibitors and proteinase K. - The higher DNA repair capacity of T-cells as reflected by UDS is confirmed therefore by the nucleoid characteristics. Apart from this suggestion, measuring nucleoid viscosity may be considered as a sensitive, simple and rapid device to detect radiation-induced DNA supercoiling phenomena. PMID- 2305028 TI - Clonogenicity of mammalian cells in hybrid spheroids: a new assay method. AB - A new in vitro method for determining the clonogenicity of mammalian cells in culture is described. The method is based on packaging clonogens into agglomerates of non-proliferating, but metabolically active, HeLa cells. These agglomerates, termed hybrid spheroids, provide an in vivo-like environment for entrapped test cells, offering a realistic system for prospective tumor control studies. Clonogenicity is determined by varying the number of test cells per hybrid spheroid so that some, but not all, spheroids give rise to macrocolonies. From the fraction of non-colony forming spheroids, the average number of clonogens per spheroid can be calculated, and the survival of irradiated test cells determined. In this fashion survival curves were obtained for HeLa, B-16 and HEp3 cells which corresponded to survival curves obtained in the conventional manner. The clonogenicity of cells, derived from a human maxillary melanoma surgical specimen was also determined by the hybrid spheroid method. With this method, plating efficiency increased in those cells which normally plate poorly, such as tumor cells, thus enabling survival measurements when this is not practical using conventional methods. PMID- 2305029 TI - The fluorescence induction kinetics as a non-destructive tool for investigating spruce treated with ozone. AB - The scattering coefficient of yellow spruce needles exceeds that of green needles by a factor of 2, whereas the fluorescence efficiency is approximately equal for both needle colours. As shown by the angular distribution the fluorescence light is diffusely emitted. However, the scattered light consists of a diffuse and a reflecting portion below 20 degrees with a ratio of the intensities of 1 : 2 at perpendicular observation (0 degrees). Control measurements show that in the rejection region the effective transmission of cut-off-filters commonly used to separate fluorescence light and excitation light exceeds the value calculated from the filter specifications by a factor of 100. Therefore, the portion of the scattered light in the measuring signal must be controlled if the fluorescence induction kinetics is measured from specimen of different colour. A device for the determination of the fluorescence induction kinetics is described which employs a He--Ne laser, a mechanically working shutter with an opening time of 4 ms for the excitation, and a computer for data storage and device control. Two filters select the fluorescence components at 685 nm and 730 nm and they reduce the portion of the scattered light in the measuring signal to 0.18% and 0.55%, respectively. In order to consider the temporal development of the fluorescence kinetics the sampling rate is reduced from 2 kHz to 1 Hz. From the data stored in the computer maximum value Fp, and steady-state-value Fs are determined for both fluorescence components. Measurements on 4-year-old spruce exposed to ozone concentrations of 0, 300 ppb, 600 ppb, and 1000 ppb were repeated every week. With increasing concentration and duration of treatment Rfd = (Fp-Fs)/Fs was decreased for both fluorescence components. With the highest ozone concentration a reduction of Rfd of 23% and 24%, respectively, was obtained for the two fluorescence components after three weeks. PMID- 2305030 TI - Studies of the mortality of A-bomb survivors. 9. Mortality, 1950-1985: Part 2. Cancer mortality based on the recently revised doses (DS86). AB - The present study, the ninth in a series that began in 1961, extends the time of surveillance 3 more years and covers the period 1950-1985. It is based on the recently revised doses, termed the DS86. The impact of the change from the T65D to the DS86 on the dose-response relationships for cancer mortality was described in the first of this series of reports. Here, the focus is on cancer mortality among the 76,000 A-bomb survivors within the LSS sample for whom DS86 doses have been estimated, with the emphasis on biological issues associated with radiation carcinogenesis. Briefly, the following is found: The excess in leukemia mortality has continued to decline with time, but remains slightly but significantly elevated in 1981-1985 in Hiroshima. For cancers other than leukemia, as a group, excess deaths continue to increase over time in direct proportion to the normal increase in natural cancer mortality with increasing age, and the relative risk seems unchanged over time within age ATB cohorts. The single exception is the cohort under 10 years of age ATB. Within this group of survivors, where the relative risk, although based on relatively few deaths, has been quite high at the higher doses, as judged by deaths before the age of 30, the risk has fallen and has remained fairly constant at a lower level thereafter. Thus the present analysis still supports, in the main, estimation of lifetime risk based on the assumption of a constant relative risk. For the same age ATD, both the relative and absolute risks are higher for younger age ATB cohorts than older ones for cancers other than leukemia. There is no statistically significant difference in excess deaths between males and females except for leukemia, though the relative risk is higher for females than for males, significantly so for cancers of the esophagus and lung, reflecting the higher background cancer rate for males. Significant dose responses are observed for leukemia, cancers of the esophagus, stomach, colon, lung, breast, ovary, and urinary bladder and multiple myeloma, as previously observed. No significant increase is demonstrable as yet for cancers of the rectum, gallbladder, pancreas, uterus, and prostate and malignant lymphoma. In the present report, cancers of the bone, pharynx, nose, and larynx, and skin except melanoma are also examined, but none of these sites show a significant increase with dose.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2305031 TI - Calculation of the proximity function of electrons. AB - A new semianalytical method to calculate the proximity function for electrons is proposed. An integral equation for the proximity function that can be solved by using information on the spatial dose distributions is obtained. The proximity function for electrons in the energy range from 10 eV to 10 keV is calculated by solving the equation numerically, using a set of electron collision cross sections for water vapor. The results are in good agreement with those obtained using the Monte Carlo method. The proposed method can be used for electrons of high energies much more efficiently than the Monte Carlo method. PMID- 2305032 TI - Multiple components of split-dose repair in plateau-phase mammalian cells: a new challenge for phenomenological modelers. AB - Split-dose experiments using starved plateau-phase Chinese hamster ovary cells have been used to investigate the kinetics of repair, expressed in terms of enhancement of reproductive survival. The results show two distinct components of repair, one having a characteristic time of just over 1 h for the removal of a lesion, the other, about 18 h. The rate at which each component removes damage and the fraction of the total damage that each removes appear to be independent of the initial amount of damage produced, i.e., dose. This lack of dose dependence is not consistent with some simple models of ionizing radiation damage and repair, such as those which assume that saturation of a repair process, depletion of enzyme pools, or the interaction of pairs of sublesions is responsible for the curvature in the dose-response relationship. However, the relationship between the amounts of each type of damage and dose appears to be consistent with models that assume that only a portion of the initial damage is directly accessible to the repair systems or that the initial damage consists of a mixture of potentially lethal and sublethal lesions. PMID- 2305033 TI - Production of DNA strand breaks by direct effects of heavy charged particles. AB - A theoretical model has been developed to calculate the yields of single- and double-strand breaks in DNA induced by direct effects of ionizing radiation. In this model, which involves no fitted parameters, elements of track structure and stopping power theory are combined with a detailed geometrical description of DNA to calculate the energy deposited by fast charged particles to DNA molecules. The average energy per interaction with a DNA molecule is estimated to be 30 eV from the available data on oscillator strength measurements. These ideas have been incorporated in a Monte Carlo computer program using Poisson statistics to treat the stochastic nature of the energy deposition processes and thereby determine the excitation and ionization states of the molecule. Each ionization reaction on the DNA backbone is assumed to lead to a DNA strand break. In our model double strand breaks result from nearby independent breaks on opposite strands. Our calculated single- and double-strand break yields compare well with measured cellular data under conditions such that direct effects are thought to dominate strand break production. PMID- 2305034 TI - Reduction of 3-methoxytyramine concentrations in the caudate nucleus of rats after exposure to high-energy iron particles: evidence for deficits in dopaminergic neurons. AB - Exposure to low doses of high-energy iron particles can alter motor behavior. The ability of rats to hang from a wire has been reported to be significantly degraded after exposure to doses as low as 0.5 Gy. In addition, deficits in the ability of acetylcholine to regulate dopamine release in the caudate nucleus (an area in the brain important for motor function) have been found. The concentrations of 3-methoxytyramine (3-MT), a metabolite of dopamine whose concentrations reflect dopamine release in vivo, were measured after rats were exposed to different doses of high-energy iron particles to gain further information about the effect of radiation on the dopaminergic system. Concentrations of 3-MT were significantly reduced 3 days after exposure to 5 Gy but returned to control values by 8 days. After 6 months, concentrations were again less than control values. Exposure to 5 Gy of high-energy electrons or gamma photons had no effect 3 days after exposure. Very high doses of electrons were needed to alter 3-MT concentrations. One hundred grays of electrons decreased 3-MT 30 min after irradiation but levels returned to control values by 60 min. Gamma photons had no effect after doses up to 200 Gy. These results provide further evidence that exposure to heavy particles can degrade motor behavior through an action on dopaminergic mechanisms and that this can occur after doses much lower than those needed for low-LET radiation. PMID- 2305035 TI - The increase in radioresistance of Chinese hamster cells cultured as spheroids is correlated to changes in nuclear morphology. AB - Chinese hamster V79 cells grown as spheroids in roller culture are more radioresistant than those grown as monolayers. The supercoiled structure of chromatin, as salt-extracted nucleoids, has been examined using flow cytometry. Irradiated viable cells from spheroid culture contain restraints to supercoil relaxation that are absent in monolayer cells. Further analysis of the chromatin organization from each growth form shows that the radioresistant spheroid cells contain a DNA-protein matrix that is more resistant to detergent-induced degradation. The increase in structural integrity may be due to the retention of a 55-60 kDa protein that is apparent in the nucleoids of spheroid, but not monolayer cells. The increase in structural integrity of the spheroid cells may explain their greater radioresistance by providing a more stable platform for high-fidelity DNA damage repair. PMID- 2305036 TI - Beta-radiation-induced resistance to MNNG initiation of papilloma but not carcinoma formation in mouse skin. AB - We have shown previously that the risk of tumor initiation, promotion, and progression in animals initiated with alkylating agents can be drastically altered by hyperthermia treatments. We show here that ionizing radiation can also alter the risk of tumor initiation by alkylating agents. Using a two-step skin tumorigenesis protocol in female SENCAR mice (initiation by MNNG, promotion with TPA), we exposed the dorsal skin of the mice to various doses of 90Sr/90Y beta radiation near the time of initiation. The radiation produced a dose-dependent reduction in the number of papillomas which appeared after TPA promotion, with about a 20% reduction in animals receiving 0.5 Gy surface dose just before initiation, about 50% reduction after 2.5 Gy, and greater than 80% at doses above 5 Gy. A dose of 2.5 Gy in animals initiated with DMBA produced no significant reduction. One skin hyperthermia treatment (44 degrees C, 30 min) along with radiation in MNNG-initiated animals partially blocked the protective effect of radiation and increased the papilloma frequency. Radiation (2.5 Gy) given either 6 days before or after MNNG initiation was less effective but still reduced papilloma frequency about 20%. In sharp contrast to the marked reduction in papilloma formation, these same animals showed no change in carcinoma frequency with any of the doses or schedules of beta radiation. MNNG initiation alone produced three types of initiated cells. One type, produced in low yield, was promotion-independent with a high probability of progression to a carcinoma and appeared unaffected by the radiation. A second type, produced in intermediate yield, was promotion-dependent and also had a high progression probability, but was likewise unaffected by the radiation. The third and most abundant type was promotion-dependent with a very low progression probability. Radiation exposure resulted in a decrease in the risk of an MNNG initiation event which led only to the third type of cell. The data therefore indicate that the risk of some, but not all, tumor-initiating events caused by alkylating agents can be reduced by an exposure to ionizing radiation. PMID- 2305037 TI - Cytotoxicity, radiosensitization, and DNA interaction of platinum complexes of thiazin and xanthene dyes. AB - Complexes of the platinum(II) tetrachlorodianion with positively charged nuclear dyes have been prepared in an effort to produce neutral molecules which could gain ready access to the nuclear DNA where the platinum(II) tetrachlorodianion could function as a radiosensitizing and a bifunctional alkylating agent. The thiazin dyes Thionin, Azure B, and Methylene Blue, the aminoxanthene dye Pyronin Y, and the thiazole dye Thioflavin have each been complexed to the platinum(II) tetrachlorodianion(PtCl4) in a ratio of 2:1(dye:PtCl4). Studies of the interaction of these complexes and of the dyes with the pBR322 plasmid superhelical DNA demonstrated that while each complex and dye readily associated with the DNA in a dose-dependent manner, only Pt(Thioflavin)2 and Thioflavin produced irreversible DNA changes (single-strand breaks). In exponentially growing EMT6 cells the cytotoxicity of these drugs was assessed in normally oxygenated and hypoxic cells at both pH 7.4 and 6.45. At concentrations ranging from 1 to 500 microM, Pt(Methylene Blue)2 was significantly more cytotoxic than the other thiazin dye complexes Pt(Thionin)2 and Pt(Azure B)2. The cytotoxicity of Pt(Thionin)2 and Pt(Methylene Blue)2 was increased in normally oxygenated and hypoxic cells at low pH. Both Pt(Pyronin Y)2 and Pt(Thioflavin)2 were more toxic than the thiazin complexes. Pt(Pyronin Y)2 was most cytotoxic to normally oxygenated cells at normal pH and hypoxic cells at low pH, while Pt(Thioflavin)2 was most cytotoxic to cells at low pH under both oxygenation conditions. In vitro studies of the radiosensitizing properties of these agents in EMT6 cells demonstrated that exposure to 100 microM for 1 h before and during irradiation (except for Pt[Thioflavin]2, which was assayed at 25 microM) resulted in enhancement rations of 2.5, 1.9, 1.5, and 1.5 for Pt(Azure B)2, Pt(Thionin)2, Pt(Pyronin Y)2, and Pt(Thioflavin)2, respectively, in hypoxic cells. In contrast, Pt(Methylene Blue)2 (and Methylene Blue) proved to be a radioprotector of normally oxygenated cells and did not sensitize hypoxic cells to the cytotoxic effects of radiation. In the FSaIIC fibrosarcoma in vivo administration of each drug at 100 mg/kg intraperitoneally (ip) 15 min prior to irradiation (except for Pt[Thioflavin]2, which was given at 1 mg/kg ip) showed that, with single radiation fractions of 10 and 20 Gy, dose-modifying factors of 2.1, 1.8, 1.5, and 1.2 were produced by Pt(Azure B)2, Pt(Thionin)2, Pt(Pyronin Y), and Pt(Methylene Blue)2, respectively, after correcting for growth delays induced by the drug alone. In comparison, misonidazole at 1 g/kg ip produced a dose-modifying factor of 1.4.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2305038 TI - Asymmetric field inversion gel electrophoresis: a new method for detecting DNA double-strand breaks in mammalian cells. AB - A new method is described for detecting DNA double-strand breaks (DSBs) that utilizes asymmetric field inversion gel electrophoresis (AFIGE). DNA purified from cells in agarose plugs is subjected to AFIGE and DNA breakage quantitated by the fraction of DNA released from the plug. To test the specificity of the method for DNA DSBs, purified DNA in agarose plugs was treated for increasing times with restriction endonuclease, XhoI. After an initial time period, the fraction of DNA released increased in direct proportion to time. This correlates with the expected response for a randomly broken DNA molecule. In contrast, treatment with the single-strand breaking agent, hydrogen peroxide, over a 1000-fold range produced no release of DNA from the plug. Thus the assay appears to be specific for DNA DSBs and was used to measure DNA breaks induced by gamma radiation. Purified DNA, irradiated in agarose plugs, exhibited a log-linear dose response up to doses that release greater than 90% DNA from the plug. When live cells were irradiated in agarose, a similar linear dose response was observed up to 40 Gy and a significant signal as low as 2.5 Gy. Also in live cells, a threefold lower percentage of DNA was released from the plug over the same dose range. However, less DNA per gray is released at doses above 40 Gy and may reflect a crosslinking effect produced by the irradiation of DNA in live cells. DNA which was "pulse labeled" was used to test the effect of DNA replication on the ability of AFIGE to detect DNA DSBs. Replicating DNA irradiated in the cell or after purification exhibited a reduced rate of release from the plug per dose of irradiation. Overall, the above results indicate that AFIGE is a sensitive method for detecting DSBs in DNA. PMID- 2305039 TI - Sensitivity of a human hybrid cell line (HeLa X skin fibroblast) to radiation induced neoplastic transformation in G2, M, and mid-G1 phases of the cell cycle. AB - The dependence of gamma-radiation-induced neoplastic transformation frequency on position in the cell cycle was measured for a human hybrid cell line (HeLa X skin fibroblast). The end point used was the induction of a tumor-associated antigen which in these cells correlates with tumorigenicity. Induction was measured in cells at G2, M, and mid-G1 phases and compared with the frequency induced in asynchronous cells. For studies of cells in G2 phase, the cells of an asynchronous population were collected for 3 h post-irradiation using the mitotic shake-off technique. For studies of cells in M and mid-G1 phases, cells were collected by mitotic harvest and then treated at the appropriate time. The data show that cells in G2 and M phase are very radiosensitive in terms of both cell killing and induction of neoplastic transformation compared to cells in mid-G1 or asynchronous populations. At a dose of 1 Gy, the transformation frequency was 10- to 20-fold higher for cells in M and G2 phase than for cells in mid-G1 or for asynchronous cells. However, the data indicate that the transformation frequencies were similar in the different phases of the cell cycle when correlated with surviving fraction. The results indicate that transformation frequency is more sensitive to changes in dose than is cell survival. PMID- 2305040 TI - Radioprotection of mice with interleukin-1: relationship to the number of erythroid and granulocyte-macrophage colony-forming cells. AB - This report presents the results of an investigation of changes in the number of erythroid and granulocyte-macrophage colony-forming cells (GM-CFC) that had occurred in tissues of normal B6D2F1 mice 20 h after administration of a radioprotective dose (150 ng) of human recombinant interleukin-1 (rIL-1). Neutrophilia in the peripheral blood and changes in the tissue distribution of GM CFC demonstrated that cells were mobilized from the bone marrow in response to rIL-1 injection. For example, 20 h after rIL-1 injection marrow GM-CFC numbers were 80% of the numbers in bone marrow from saline-injected mice. Associated with this decrease there was a twofold increase in the number of peripheral blood and splenic GM-CFC. Also, as determined by hydroxyurea injection, there was an increase in the number of GM-CFC in S phase of the cell cycle in the spleen, but not in the bone marrow. Data in this report suggest that when compared to the spleen, stimulation of granulopoiesis after rIL-1 injection is delayed in the bone marrow. Also, the earlier recovery of GM-CFC in the bone marrow of irradiated mice is not dependent upon an increase in the number of GM-CFC at the time of irradiation. PMID- 2305041 TI - In vitro radiosensitivity of human diploid fibroblasts derived from women with unusually sensitive clinical responses to definitive radiation therapy for breast cancer. AB - Between January 1985 and December 1986, 811 patients were treated for carcinoma of the breast at the Joint Center for Radiation Therapy by an identical protocol. Of these 811 patients, five patients (0.6%) were identified as having an unusually sensitive clinical response to routine external beam irradiation. This unusual clinical response was characterized by severe skin erythema and edema during the first few weeks of treatment, requiring treatment breaks. Skin fibroblast cell strains were established from these five women as well as from six women with a normal clinical response to breast irradiation (chosen at random from the population of 811 patients). Radiation survival parameters were determined by a colony formation assay from complete survival curves in coded and blinded samples. Cells from the sensitive patients were significantly more sensitive to the cytotoxic effects of radiation in vitro as determined by the parameters D0, D, D10, and n, than were the strains derived from patients with a normal response. We conclude that an unusually severe response to standard fractionated radiotherapy may be associated with greater intrinsic radiation sensitivity of the individual's somatic cells. PMID- 2305042 TI - Mammography screening: technology, radiation dose and risk, quality control, and benefits to society. A symposium conducted during the scientific assembly and annual meeting of the Radiological Society of North America. Chicago, December 1988. Proceedings. PMID- 2305043 TI - Estimation of radiation risk from screening mammography: recent trends and comparison with expected benefits. AB - On the basis of recent epidemiologic studies, the National Institutes of Health in 1985 provided a new estimate for radiation risk to the breast that employed a relative risk model and acknowledged greater dependence on age at exposure. Lifetime risks from a single mammogram may be calculated from this estimate and are lower than those based on the previous 1977 National Cancer Institute estimate. Possible years of life expectancy lost from annual mammography beginning at age 40 years may also be calculated and are negligible compared with estimates for years of life expectancy gained from such screening. PMID- 2305044 TI - Standardization of image quality and radiation dose in mammography. AB - Image quality is the cornerstone to the practice of high-quality mammography. To ensure high quality in the practice of mammography, the American College of Radiology has established a voluntary program for the accreditation of mammographic screening sites. Between August 15, 1987, and February 1, 1989, 647 mammography units completed the accreditation program. Data collected from those units are presented, demonstrating that broad ranges of image quality and dose currently exist among mammographic screening sites. Reasons are discussed for the wide ranges observed, and steps are proposed to narrow the ranges of image quality and dose in the practice of mammography. PMID- 2305045 TI - Radiographically guided fine-needle aspiration of nonpalpable breast lesions. AB - Radiographically guided fine-needle aspiration (X-FNA) in 215 nonpalpable, mammographically detected breast lesions was performed by means of a coordinate grid localization system. Aspirates were categorized either into four cytologic groups or as simple cysts. Based on the most stringent cytologic criteria, the maximum sensitivity for detection of carcinoma was 97% and the specificity was 94%. However, according to these strict cytologic criteria, only 46% of aspirates contained representative material. Based on less stringent cytologic criteria, the maximum sensitivity was 68% and the specificity was 97%. Forty-one of 74 lesions proved to be malignant at biopsy. Thirty-four patients did not complete adequate mammographic follow-up. High sensitivity and specificity can be achieved with X-FNA. However, management decisions ultimately require integration of mammographic findings with cytologic results. Close cooperation among mammographer, surgeon, cytopathologist, and patient is mandatory for successful results. PMID- 2305046 TI - Temporomandibular joint dysfunction: correlation of MR imaging, arthrography, and arthroscopy. AB - This prospective study correlated the results of magnetic resonance (MR) imaging, arthrography, and arthroscopy in 27 patients with clinically suspected temporomandibular joint (TMJ) dysfunction. Open surgical confirmation was available in 12 TMJs. The variables assessed with each modality were disk position and morphology, disk perforation, joint adhesions, and degenerative joint disease. MR imaging was superior to dual joint arthrography with arthrotomography in delineation of the disk position. MR imaging accurately demonstrated the disk position in 11 joints (92%); arthrography was accurate in nine of the 12 joints (75%) with surgically confirmed dysfunction. Disk perforations and joint adhesions were not demonstrated with MR imaging. Arthroscopy was superior to arthrography and MR imaging in the detection of disk perforations, joint adhesions, and early degenerative changes along the articular eminence and glenoid fossa. The authors believe MR imaging should constitute the first line of imaging because it provides accurate information about disk position in a noninvasive manner. In most cases, information obtained with MR imaging is adequate in deciding whether to institute conservative or surgical management; in difficult cases, triple correlation may be needed. PMID- 2305047 TI - MR findings of cartilage invasion by laryngeal cancer: value in predicting outcome of radiation therapy. AB - Thirty-nine patients who underwent radiation therapy with curative intent for laryngeal cancer were examined before treatment with magnetic resonance (MR) imaging, between November 1985 and January 1987. MR findings of cartilage invasion were correlated with the effectiveness of radiation treatment. Adequate interpretation of the MR examinations was not possible in four cases (10%). Cartilage invasion was found in 16 of the 35 remaining patients and was found even in small glottic lesions, clinically staged as T1b and T2. Laryngeal cancer recurred in 10 of the 16 patients with cartilage invasion shown by MR imaging. The presence of even small foci of invasion of the thyroid cartilage by laryngeal cancer appeared to increase the subsequent risk of tumor recurrence. Cartilage invasion seen at MR imaging might therefore shift the preference to partial laryngectomy as the initial treatment for small glottic tumors. Alternatively, radiation therapy alone would appear to require stringent follow-up to detect possible recurrence. PMID- 2305048 TI - The brain in healthy aged individuals: MR imaging. AB - Twenty-four healthy aged individuals with above-average intellectual function were studied with use of a low-field-strength (0.02-T) magnetic resonance (MR) imager. The group was carefully selected so as not to include persons with signs of arteriosclerotic diseases, major somatic disease, or a history of brain disease or dementia in the family. The width of the subarachnoid spaces and lateral ventricles, as well as the frequency and degree of brain white-matter lesions, were described with the use of a visual rating scale. White matter lesions were found in less than 9% of the subjects. The lateral brain ventricles were enlarged in 8% of all individuals and the cortical cerebrospinal fluid (CSF) spaces in more than 40% of all individuals. Moreover, T1 and T2 were estimated in different brain areas, and a positive correlation between T1 in the frontal white matter and age was found. A computer-assisted classification procedure was used to estimate brain tissue and CSF areas. The results of this procedure strongly correlated with the visually estimated ventricular size. PMID- 2305049 TI - Pituitary gland: MR imaging of physiologic hypertrophy in adolescence. AB - The size and shape of pituitary glands in 169 children, adolescents, and young adults were analyzed with T1-weighted sagittal magnetic resonance (MR) images. In patients younger than 12 years old, no pituitary gland was found to be more than 6 mm in height. In adolescents, definite evidence for physiologic (pubertal) pituitary hypertrophy was seen in both sexes, although it was much more prominent in girls. The pituitary glands of four of 32 teenage girls measured 8-10 mm, but no teenage boy had a gland taller than 7 mm. Young adults aged 21-30 years had significantly (P less than .05) smaller glands than teenagers of the same sex. Significant (P = .0001) variations in the shape of the pituitary glands according to patient age and sex were also noted. Convex upper margins were seen in 56% of teenage girls, while this shape was noted in only 18% of the remaining patients of either sex. In eight of 32 teenage girls (25%) the pituitary glands were nearly spherical on sagittal images; this shape was not recorded in any other group. The normal maturation sequence of the pituitary gland apparently involves a period of physiologic hypertrophy in teenagers. This is manifest in girls by a significant change in both pituitary size and shape, while the glands of boys undergo a transformation in size only. PMID- 2305050 TI - Endovascular treatment of intracranial aneurysms with a new silicone microballoon device: technical considerations and indications for therapy. AB - Treatment of complex intracranial aneurysms by means of interventional neurovascular techniques is now being performed with a newly developed silicone detachable-microballoon device. The balloon is composed of unique silicone elastomers that are extremely soft and malleable. It therefore conforms to the blood vessel lumen or aneurysm wall and reduces the risk of rupture. It is affixed onto a 2.0-F catheter and can be either directed by flow or guided with the catheter. For aneurysms with a well-defined neck, the balloon is placed directly into the aneurysm, inflated with 2-hydroxyethyl methacrylate for permanent solidification, and detached. The aneurysm is thus excluded from the circulation, and the parent vessel is preserved. For aneurysms without a well defined neck, test occlusion can be performed, followed by permanent balloon occlusion of the parent vessel. This balloon technique has been successfully used to treat aneurysms in both the anterior and posterior circulations, where standard neurosurgical techniques have failed, and in surgically inaccessible anatomic locations. PMID- 2305051 TI - Olivopontocerebellar atrophy: MR diagnosis and relationship to multisystem atrophy. AB - Clinical diagnosis of olivopontocerebellar atrophy (OPCA) must be confirmed by radiologic demonstration of atrophy in an appropriate distribution. OPCA may be associated with degeneration of other systems in multisystem atrophy (MSA). The authors report 23 cases of OPCA, eight of which were associated with MSA. Atrophy involved the cerebellum, pons, and middle cerebellar peduncles in all cases. On intermediate and T2-weighted magnetic resonance (MR) images, abnormal signal intensity was always observed in the transverse pontine fibers, middle cerebellar peduncles, and cerebellum, structures known from pathologic study to degenerate in OPCA. Pyramidal tracts and superior cerebellar peduncles stood out because of their normal signal intensity. Of the eight patients with MSA, four also had variable abnormal signal intensities in the putamen. The authors believe that the combination of atrophy and abnormal signal intensity in the appropriate distribution strongly supports the diagnosis of OPCA. In some cases, MR imaging may demonstrate involvement of different systems, thus confirming the diagnosis of MSA. PMID- 2305052 TI - Thin-walled cavities, cysts, and pneumothorax in Pneumocystis carinii pneumonia: further observations with histopathologic correlation. AB - Thin-walled pulmonary cystic lesions were found in five immunocompromised patients, four with acquired immunodeficiency syndrome (AIDS). Four patients had Pneumocystis carinii pneumonia (PCP), and one had pulmonary lesions and disseminated P carinii infection. Two patients demonstrated P carinii within necrotizing, thin-walled, smaller intraparenchymal cavities lined by organisms, exudate, and chronic inflammation. Larger, typically apical and subpleural cysts, lined by fibrosis and/or alveolar parenchyma with little inflammation, were also found during acute episodes. The larger subpleural cysts can arise via rupture of intraparenchymal necrotizing cavities into the subpleural area. Pneumothorax in the four patients with AIDS could not be cured by close thoracostomy drainage; all required pleurodesis. The cysts persisted in cases that were followed up. All cysts were more obvious and numerous with computed tomography (CT), especially with 1.5-mm collimation. CT may be indicated in immunocompromised patients with unexplained pneumothorax or when tube thoracostomy has failed and surgery is being considered, as it can positively influence the operative approach. PMID- 2305053 TI - Thoracic manifestations of Wegener granulomatosis: diagnosis and course. AB - A combination of cytotoxic and corticosteroid therapy has dramatically improved the long-term survival of patients with Wegener granulomatosis. With extended survival, patients now experience diverse cardiopulmonary abnormalities that represent primary or secondary manifestations of the disease or that result from diagnosis and treatment. To evaluate these abnormalities, the authors reviewed the medical histories and chest radiologic findings of 19 patients with the histologic diagnosis of Wegener granulomatosis. In these patients thoracic images demonstrated parenchymal nodules or consolidations with cavitation, diffuse interstitial disease, mediastinal or hilar adenopathy, and isolated stenoses of the larynx or tracheobronchial tree. Intrathoracic relapse occurred in 18 cases; in one-third of these patients, findings at relapse differed from those at initial presentation. Complications from diagnosis or therapy occurred in nine patients. Pulmonary infection was the most frequent complication causing morbidity and was often clinically indistinguishable from the primary disease; it complicated relapse in five patients. The successful radiologic follow-up of patients with Wegener granulomatosis requires a consideration of the varied thoracic manifestations of both the primary disease and the complications of its treatment. PMID- 2305054 TI - Counterclockwise exit of cardiac pacemaker leads: sign of pulse-generator flip. AB - Clockwise exit of pacing leads from transvenous cardiac pacemakers is generally essential for proper function. The authors report a case in which counterclockwise exit of the pacing leads signified a 180 degree flip of the pulse generator. Three types of pacing system malfunction can result from pacemaker flip. PMID- 2305055 TI - Limited correlation of left ventricular end-diastolic pressure with radiographic assessment of pulmonary hemodynamics. AB - Left ventricular end-diastolic pressure (LVEDP) is a reliable indicator of the diastolic function of the left ventricle. The purpose of this study was to correlate the radiographic assessment of pulmonary hemodynamics with LVEDP. The study population consisted of 104 consecutive patients with four categories of LVEDP: less than 13 mm Hg (n = 26), 13-19 mm Hg (n = 30), 20-24 mm Hg (n = 24), and more than 24 mm Hg (n = 24). Chest radiographs obtained within 24 hours of cardiac catheterization were assessed for evidence of congestive heart failure (CHF) by three experienced radiologists. Findings were graded from 0 to 3 (normal to abnormal) on the basis of the following signs of CHF: redistribution, perihilar and perivascular haze, peribronchial cuffing, pulmonary artery-bronchus ratio, septal lines, subpleural edema, air-space edema, pleural effusion, cardiomegaly, and overall radiographic assessment of CHF. A consensus report was then generated. In patients with LVEDP over 20 mm Hg, 38% did not show CHF in the overall assessment. Correlation between radiographic signs of CHF and LVEDP was limited. PMID- 2305056 TI - Primary intrathoracic extraosseous osteogenic sarcoma: report of three cases. PMID- 2305057 TI - Abdominal aorta and renal artery stenosis: evaluation with MR angiography. AB - A blinded, prospective study with magnetic resonance (MR) angiography was performed to study patients who had undergone abdominal aortography. In 55 renal arteries among 25 patients, MR angiography had a sensitivity of 100% for detecting renal artery stenosis of 50% or greater and a specificity of 92%. With MR angiography, the degree of renal artery stenosis was overgraded in four of 55 renal arteries: Mild stenosis was overgraded as moderate stenosis in two arteries and as a severe stenosis in one, and a moderate stenosis was overgraded as a severe stenosis in one. The number of renal arteries was correctly determined in all cases. The renal arteries could be well evaluated only in the proximal third of the vessel, precluding detection of more distal stenoses. Atherosclerotic plaque uniformly appeared dark on gradient-echo images and was easily differentiated from bright, flowing blood in the aortic lumen. MR angiography enabled correct grading of the presence of atherosclerotic plaque and stenoses of the abdominal aorta in 22 of 25 patients (88%). The authors conclude that MR angiography has the potential to be a useful screening technique for patients with suspected renal artery stenosis and disorders of the abdominal aorta, but further clinical studies are warranted. PMID- 2305058 TI - First-pass cardiac perfusion: evaluation with ultrafast MR imaging. AB - The authors studied cardiac perfusion by administering gadolinium diethylenetriaminepentaacetic acid (DTPA) in conjunction with an ultrafast imaging technique that produces strongly T1-weighted images. The method consisted of a 180 degrees inversion pulse, followed by a gradient-echo acquisition with a very short repetition time (less than 4 msec). Each image was acquired throughout a small fraction of the cardiac cycle. The method was applied in an isolated perfused rat heart model (acquisition time = 116 msec) and in human subjects without known cardiac disease (acquisition time = 125 msec). Fast, high resolution images (128 X 128 matrix) were created by combining sequentially acquired small matrixes. After bolus administration of Gd-DTPA in the perfused rat heart model, contrast was pronounced between the nonperfused myocardium and perfused normal myocardium. First-pass wash-in and washout phases of the contrast material were observed in the perfused rat heart model and in human subjects. Results demonstrated the clinical feasibility of first-pass perfusion studies of the heart. The studies can be performed on a conventional whole-body imaging system with standard hardware. PMID- 2305059 TI - Normal left ventricular dimensions and function: interstudy reproducibility of measurements with cine MR imaging. AB - The authors evaluated the reproducibility of measurements of ventricular dimensions obtained with cine magnetic resonance (MR) imaging performed on two occasions in 11 healthy subjects. Two reviewers analyzed the studies in a blinded fashion to determine interobserver and interstudy variability of measurements of left ventricular (LV) mass, volume, ejection fraction, and systolic wall stress. LV mass showed good reproducibility between studies, with 3.6% and 3.8% variability for LV end-systolic mass for the two observers. LV end-diastolic volume varied by 5.2% and 3.9%, and LV end-systolic volume, by 9.7% and 0.9%. Variability for LV ejection fraction was 5.0% and 4.9%. The largest interstudy variability was end-systolic wall stress, 11.1% and 13.5%, which was due mostly to changes in arterial pressure between the two studies. It is concluded that anatomic and functional measurements from cine MR images are reproducible between studies. The small interstudy variability is likely related to the fact the measurements are derived directly from cine MR images that encompass the entire heart rather than depend on measurements of only sample images and the use of geometric models. PMID- 2305060 TI - Display of CT studies on a two-screen electronic workstation versus a film panel alternator: sensitivity and efficiency among radiologists. AB - Prototype electronic workstations incorporated in networks linking computed tomographic (CT) and magnetic resonance imaging systems are being developed. The authors compared observer efficiency and sensitivity in reading body CT studies from a two-screen workstation (1,000-line monitors and 12-bit dynamic range in image memory) and conventional film panel alternator. The two-screen workstation displayed 32 images at a matrix resolution of 256 x 256 or eight images at a matrix resolution of 512 x 512 simultaneously. Ninety-six images with a matrix resolution of 512 x 512 could be displayed simultaneously at the film panel alternator. Four observers read images from 20 cases, 10 with repeat examinations, in a randomized viewing sequence. There was an average of 32 images per case. Reporting time was less with the film panel alternator (average, 5.08 minutes) than with the workstation (average, 6.66 minutes). There was improved sensitivity for all observers in reading from the film panel alternator (range, 1%-12%) (P less than .05). In complex cases evaluated by means of body CT, the current prototype two-screen electronic workstation is limited by display capabilities. PMID- 2305061 TI - Receiver operating characteristic analysis of chest image interpretation with conventional, laser-printed, and high-resolution workstation images. AB - The differences among radiologists in interpreting conventional and digitized images obtained with different radiologic procedures is an important research issue in these times of implementation and growth of the digital modalities. The authors performed a multiobserver study to determine the performance of radiologists reading posteroanterior conventional radiographs, digitized radiographs laser printed onto film, and images displayed on a high-resolution workstation (video monitor). A total of 300 images were evaluated by seven radiologists who recorded their ordinal confidence rating of the presence or absence of one or more of the following abnormalities: interstitial disease, nodule, and pneumothorax. Receiver operating characteristic analysis showed statistically significant differences for the detection of different abnormalities by individual readers. The group as a whole showed a significant reduction in observer performance for the detection of interstitial disease and pneumothorax when the laser-printed radiographs or the workstation was used rather than conventional radiographs. PMID- 2305062 TI - Gallstone fragmentation with contact electrohydraulic lithotripsy: in vitro study of physical and technical factors. AB - To identify physical and technical factors that have an effect on fragmentation, the authors performed in vitro contact electrohydraulic lithotripsy (EHL) on gallstones 10 mm or larger in size. Of 122 gallstones, 113 (93%) could be fragmented with 1-46 pulses from a 3-F electrode (average, 10 pulses). Only 12 of the 113 stones could be fragmented with a single spark. Of the nine stones that did not fragment with 50 pulses from a 3-F electrode, four were larger than 30 mm in diameter, and five were seen at radiography to be heavily calcified; all of these stones were fragmented with five or fewer pulses from a 9-F electrode. Stone capture in a wire basket facilitated fragmentation of gallstones of all sizes, but particularly those stones 15 mm or larger. Contact EHL could be performed as well in a 1:1 dilute diatrizoate irrigating solution as in 1:6 normal saline. A significantly greater number of pulses was required to fragment gallstones 15 mm in diameter or larger compared with stones smaller than 15 mm (P less than .01). In addition, stones 15 mm or smaller had a greater tendency to fragment into "gravel" (ie, fragments measuring 2 mm or less), while EHL of stones larger than 15 mm produced larger, discrete fragments of approximately equal size (P less than .05). EHL of heavily calcified gallstones required a significantly greater number of pulses than EHL of less calcified or noncalcified stones (P less than .002). PMID- 2305063 TI - Hepatic cirrhosis and hepatitis: MR imaging enhanced with superparamagnetic iron oxide. AB - Superparamagnetic iron oxide was applied as a reticuloendothelial contrast agent in the diagnosis of cirrhosis and hepatitis in seven patients. Three patients had compensated cirrhosis, and four had active hepatitis. T1- and T2-weighted spin echo magnetic resonance images were obtained before and 1 hour after the administration of iron oxide. Eight patients without diffuse liver disease served as a control group. Normal liver tissue showed a 75% +/- 9% reduction in signal intensity after the administration of iron oxide, and the liver appeared homogeneously hypointense. Cirrhotic liver tissue showed a smaller response (P less than .05) to iron oxide, with a 52% +/- 13% reduction in liver signal intensity. Inhomogeneous structures could be observed in enhanced images and are thought to represent fibrous bands or regenerating nodules. Liver tissue with active hepatitis showed a markedly reduced response to iron oxide (11% +/- 2%) (P less than .05), and the parenchyma appeared homogeneous. The authors conclude that the uptake of iron oxide particles is inhomogeneously altered in cirrhosis because of structural changes and homogeneously decreased in hepatitis because of functional changes of hepatic parenchyma. PMID- 2305064 TI - von Hippel-Lindau disease: radiologic screening for visceral manifestations. AB - The visceral manifestations of von Hippel-Lindau (VHL) disease can cause significant morbidity and mortality. The authors prospectively screened 37 persons from a single kindred. Twenty-five subjects underwent abdominal ultrasound (US), contrast material-enhanced abdominal computed tomography (CT), and nonenhanced abdominal magnetic resonance (MR) imaging. Eight subjects younger than 16 years of age underwent abdominal US and MR imaging only. Scrotal US was employed in 25 male patients. Eleven subjects had renal cysts or tumors. Contrast enhanced CT depicted renal abnormalities in 10 of these subjects, US in seven, and MR imaging in nine. Among 12 subjects with pancreatic cysts or tumors, CT showed pancreatic abnormalities in all 12, US in nine, and MR imaging in nine. Three subjects (mean age, 34.5 years) had renal tumors, and three had pancreatic masses. Scrotal US revealed epididymal cystadenomas in seven subjects; two of these tumors were surgically verified. A combination of contrast-enhanced CT and scrotal US in male patients appears to be the best way to screen for visceral manifestations of VHL disease. PMID- 2305065 TI - Cervical incompetence: preliminary evaluation with MR imaging. AB - The ability of magnetic resonance (MR) imaging to demonstrate cervical incompetence in nonpregnant women was investigated in a prospective study of 41 volunteers referred in random order. These included 20 patients with normal cervices, 11 with cervical incompetence of traumatic or congenital origin, and 10 with clinically small cervices due to in utero diethylstilbestrol (DES) exposure. On MR images of the normal patients, cervical length was 33.0 mm +/- 1.0 (mean +/ standard error of the mean) and the width of the internal cervical os was 3.3 mm +/- 0.1. In patients with cervical incompetence, the cervical length did not significantly differ from those in the normal group. However, the internal cervical os was significantly wider (4.5 mm +/- 0.3, P less than .001), and localized irregularity of the endocervical canal was demonstrated in two patients. The MR appearance of the cervical stroma varied from normal, uniformly low signal intensity (n = 4) to uniformly (n = 3) or partially (n = 4) medium-to high signal intensity on T2-weighted images. In the patients with in utero DES exposure, the mean length of the cervical canal (22.9 mm +/- 1.7) was significantly shorter than that of the normal group. The width of the internal cervical os and the MR signal intensity of the cervical stroma were normal. In summary, MR findings of a cervical length shorter than 3.1 mm (95% confidence limit), an internal cervical os wider than 4.2 mm (95% confidence limit), or abnormal signal intensity in the cervical stroma are highly suggestive of incompetent cervix and should assist in planning further therapeutic decisions. PMID- 2305066 TI - Descent of the bladder neck: a urographic finding in denervation of the urethral sphincter in children with myelodysplasia. AB - The urographic position of the neck of the bladder in relation to the pubic symphysis was correlated with lower motor neuron (LMN) denervation of the urethral sphincter as detected with electromyography in 65 infants and children with myelodysplasia. Descent (prolapse) of the bladder (bladder neck below the upper margin of the pubic symphysis) was present in 30 (46.2%) patients. Prolapse was both more frequent and tended to be more severe in girls. Complete LMN denervation of the urethral sphincter was present in 25 (83.3%) of the 30 patients with prolapse and in only four (11.4%) of 35 with a normally positioned bladder. Conversely, 25 (86.2%) of the 29 patients with complete LMN denervation of the sphincter had prolapse as compared with only five (13.9%) of 36 patients with partial or no LMN denervation of the sphincter. Although not as precise as urodynamic testing, significant descent of the bladder neck is a reliable urographic finding of complete LMN denervation of the external urethral sphincter in infants and children with myelodysplasia. PMID- 2305067 TI - Nondisease. PMID- 2305068 TI - Osteophytosis of the knee: anatomic, radiologic, and pathologic investigation. AB - Although the radiologic manifestations of degenerative disease of the knee have been investigated, the distribution of marginal and central osteophytes has not been defined. This study included (a) 50 consecutive patients with osteoarthritis of the knee in whom routine and specialized projections were obtained prospectively, (b) 25 patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease whose knee radiographs were retrospectively reviewed, and (c) four cadaveric knees that were dissected to assess pertinent anatomy. In this study the importance of the tunnel view in the evaluation of osteoarthritis and CPPD crystal deposition disease is demonstrated, the distribution of and the relationship between marginal and central osteophytes are discussed, and two new radiologic signs are described. As both marginal and central osteophytes may simulate intraarticular bodies, the recognition of these outgrowths is of clinical importance. PMID- 2305069 TI - Effect of trabecular bone on the appearance of marrow in gradient-echo imaging of the appendicular skeleton. AB - This prospective study evaluated the effect of trabecular bone on the appearance of marrow in gradient-echo (GRE) images of the appendicular skeleton in vivo at high magnetic field strength. Magnetic resonance (MR) imaging of 10 normal extremities in five patients was performed with spin-echo (SE) and GRE sequences. The latter were obtained with gradient recalled acquisition in a steady state. SE and GRE sequences had identical spacing and planes of imaging. Cortical bone appeared as a signal void regardless of the pulse sequences and parameters. Marrow in contact with trabecular bone exhibited a shortened effective transverse relaxation time (T2*) and resultant signal loss because of local field inhomogeneities where mineralized matrix interfaced with it. This T2* effect was increased in regions with more trabecular bone (epiphysis) than regions with little trabecular bone (diaphysis). A low signal intensity on GRE images may represent fatty marrow with a high content of trabecular bone and should not be interpreted only as hematopoietic marrow. PMID- 2305070 TI - Porous-coated anatomic total hip prostheses: radiographic analysis and clinical correlation. AB - The radiographic changes of 46 bone-ingrowth, porous-coated anatomic total hip prostheses were reviewed and compared to the clinical outcome. The average postoperative follow-up was 32 months. The radiographic features that were assessed included subsidence; periprosthetic lucencies; periosteal, endosteal, and heterotopic new bone; loose beads; implant position; and tightness of fit. Clinical results were based on the Harris hip score. All acetabular components fared well. Three of the femoral stem components needed revision. The radiographic finding that correlated best with outcome was subsidence of more than 10 mm, especially if it continued to increase more than 1 year after surgery. Other findings related to failure were loosely placed femoral stems and the presence of loose beads. However, subsidence was such a powerful predictor of clinical outcome, and the other features were so weak, that combinations of variables did not improve the assessment of outcome. Close attention should be paid to subsidence in follow-up studies. PMID- 2305071 TI - Nondisplaced fractures: spatial resolution requirements for detection with digital skeletal imaging. AB - Fifty-six radiographs of nondisplaced or minimally displaced fractures of the extremities and an equal number of studies with normal findings were selected and digitized to produce spatial resolution varying from 5.75 to 0.72 line pairs per millimeter (1p/mm), corresponding to pixel sizes ranging from 0.08 to 0.64 mm. The conventional and digitized images were evaluated by 10 radiologists, who gave their decision confidence on a graded scale. Receiver operating characteristic analyses were performed from these data to compare the digital images with the conventional radiographs. There was a progressive improvement in observer performance as the pixel size decreased. A pixel size greater than 0.16 mm (2.88 1p/mm) resulted in a significant loss of diagnostic accuracy in comparison with conventional radiographs. Specific fractures in which a larger pixel size adversely affected the evaluation included torus injuries, corner fractures in child abuse, minimal avulsion injuries, and fractures that demonstrated only trabecular disruption. PMID- 2305072 TI - Target pedicle of T-12: radiologic-anatomic correlation. AB - The authors prospectively studied 250 consecutive thoracic and lumbar spinal radiographic examinations and 56 dried skeletons to elucidate the peculiar target appearance in the pedicle of T-12 and occasionally T-11. Target pedicles were seen in 13 of the spines (23%) and in 85 of the 250 radiographic examinations (34%). Similar target pedicles were observed at T-11 in two radiographic examinations and in one spine. Anatomic correlation revealed that the inferior and lateral tubercles contribute to the ring shadow within the pedicle. PMID- 2305073 TI - Free-response methodology: alternate analysis and a new observer-performance experiment. AB - The authors review the recently introduced method for analyzing free-response receiver operating characteristic (FROC) observer-performance experiments. These experiments allow multiple abnormalities and observer responses per image and require correct localization for true-positive events. A fundamental plot, the alternative FROC (AFROC), is emphasized, the area under which is a natural index of performance for measuring FROC observer performance. The authors show that it is possible to analyze free-response data in more general ways. The first method, AFROC analysis, involves scoring FROC images in a different way. The second method involves a new observer-performance experiment, the free-response forced error (FFE) experiment. FROC and AFROC analysis was applied to several FROC data sets, and simultaneous FROC-AFROC-FFE experiments were performed with several radiologist observers to test the three methods. The methods were found to be in good agreement with one another. PMID- 2305074 TI - Cerebral metastases: value of reirradiation in selected patients. AB - Fifty-two adult patients were selected to receive a second course of cranial radiation therapy to relieve symptoms caused by recurrent cerebral metastases. To be selected, patients had to (a) have remained in relatively good general condition for at least 4 months after their initial course of radiation therapy and (b) experience renewed deterioration of their neurologic condition. Initial treatment typically consisted of 3,000 cGy administered in 10 fractions over 2 weeks to the whole brain. Reirradiation most commonly consisted of 2,500 cGy in 10 fractions. Twenty-two patients (42%) responded to reirradiation and improved by at least one level in their neurologic function status. Survival after second therapy averaged 5 months. The authors conclude that reirradiation of cerebral metastases should be considered for patients who remain in good general condition but who experience neurologic deterioration 4 or more months after satisfactory response to initial palliative cerebral radiation therapy. PMID- 2305075 TI - Selection and training of radiology researchers. PMID- 2305077 TI - Whither radiology? Wither radiology? PMID- 2305076 TI - Adjustable field shaping for external-beam radiation therapy. AB - A new, simple method for adjustable field shaping for external-beam radiation therapy is described. The system employs shielding blocks attached to specially designed flanges and blocking tray. The system allows a wide latitude of placement of the blocks on the tray. The blocking system is cost-effective and allows rapid setup of treatment fields. It also allows daily blocking adjustment if required and has been shown to produce high-quality reproducible fields in clinical use. PMID- 2305078 TI - Radionuclide thrombus imaging. PMID- 2305079 TI - Scintigraphy of renal trauma. PMID- 2305080 TI - Appropriate use of names for MR contrast media. PMID- 2305081 TI - Plaque modification with tetracycline: enhanced tissue ablation with the excimer laser. AB - Tetracycline has been shown to collect selectively in atherosclerotic plaque and is a known photosensitizing agent. To determine if tetracycline enhances the photoablative effects of the ultraviolet xenon-fluorine excimer laser, the authors exposed four cadaveric aortic samples to tetracycline and four to only normal saline. Ninety-three sites in the samples were subjected to laser energy and analyzed with light microscopy for crater depth and width and for degree of thermal injury. Forty-three of the sites were histologically normal, and 50 were atherosclerotic. Crater depth did not differ significantly in atherosclerotic and normal sites not exposed to tetracycline. Atherosclerotic sites exposed to tetracycline showed significantly deeper craters compared with those in normal, exposed sites. The effects of tetracycline exposure and histologic characteristics (normal vs atherosclerotic) on crater width and thermal injury were independent and additive. When the excimer laser is used for treatment, tetracycline can definitely enhance atherosclerotic plaque ablation. PMID- 2305083 TI - Animal model for fluoroscopically guided laser application in the biliary tree. AB - The purpose of this project was to develop an animal model for a fluoroscopically guided application of the contact neodymium-yttrium aluminum garnet (Nd-YAG) laser in the bile duct and identify the factors affecting the extent of damage to the duct wall. This model permits cholangiographic visualization of the duct during laser application. Laser damage is limited by using contact probes and firing the laser while slowly pulling the probe proximally into the duct. Sixteen common bile duct laser burns were produced in 14 dogs. Power settings of 8-25 W were used. The tension of the contact probe along the duct wall, termed "wall tension," was varied through intraoperative manipulation in order to mimic a variety of ductal geometries that might be encountered in clinical use. The authors produced duct damage ranging from a superficial burn to perforation. Power and wall tension were the most important factors in determining the depth and circumference of damage, and the use of 15 W or less did not perforate the duct. PMID- 2305084 TI - Transjugular intrahepatic portacaval stent shunt: preliminary clinical results. AB - A percutaneous transjugular, intrahepatic portacaval shunt was created by means of a combined jugular and transhepatic approach. In the hepatic tissue track joining the portal and hepatic veins balloon-expandable stents were placed. Two of three patients with life-threatening variceal bleeding and Child C liver cirrhosis benefited from the procedure. One patient in severe hepatorenal failure prior to the procedure died 11 days after the shunt procedure of pulmonary complications. This procedure may be a promising alternative to current therapy in high-risk patients with esophageal bleeding. PMID- 2305082 TI - Optimization of gradient-echo imaging parameters for intracaval filters and trapped thromboemboli. AB - Flow-phantom magnetic resonance (MR) gradient-echo (GRE) imaging at 1.5 T was performed on a titanium Greenfield filter containing trapped blood clots with a high concentration of either deoxyhemoglobin (DHb) or methemoglobin (MHb), simulating acute and older thromboemboli, respectively. Flip angle, repetition time (TR), and echo time (TE) were varied, and a contrast-to-noise ratio between trapped clots and flowing fluid (clot-flow contrast) was determined for each set of imaging parameters. Use of very low flip angles (less than or equal to 10 degrees) rendered MHb clots indistinguishable from flowing fluid. In general, DHb clots displayed greater clot-flow contrast than MHb clots regardless of flip angle. With increasing TE values, T2* effect was observed with MHb clots, and magnetic susceptibility artifacts increased. Overall, optimum clot-flow contrast for imaging of both DHb and MHb clots was achieved with a flip angle of 45 degrees-60 degrees, a TR of 50 msec, and the shortest TE possible. Using GRE parameters similar to the optimum parameters determined in vitro, the authors imaged four patients with nickel-titanium Simon filters and one dog with a titanium Greenfield filter. MR imaging was successful in demonstrating filter location, caval patency, and the presence and extent of intraluminal thrombus. PMID- 2305085 TI - Hepatic bilomas due to hepatic artery thrombosis in liver transplant recipients: percutaneous drainage and clinical outcome. AB - During the past 4 years, the authors performed catheter drainage in 15 patients (five adults and 10 children) with 16 hepatic allografts who had intrahepatic bilomas after occlusion of the hepatic artery. Ten of the 16 (62%) allografts (in four adults and six children) were replaced within 4 months of drainage: Nine were replaced because of biliary sepsis or abscess, and one was replaced because of the absence of biliary-enteric communication. Most of these patients had cholangiographic evidence of extensive bile duct necrosis. In two patients, retransplantation was avoided for longer than 2 years. One of these needed a new liver because of multiple central biliary strictures. Four patients have now lived for 30-44 months since initiation of drainage without needing new livers. Despite drainage, the outcome of most of these allografts has been poor. However, in some liver transplant recipients who have had hepatic artery thrombosis, biloma drainage can prolong allograft survival and prevent retransplantation. PMID- 2305086 TI - Spontaneous hepatic hemorrhage in preeclampsia: treatment with hepatic arterial embolization. AB - Four patients with spontaneous rupture of the liver due to preeclampsia of pregnancy underwent diagnostic angiography followed by successful transcatheter embolization of the hepatic artery with gelatin particles. All patients stopped bleeding and were discharged in good condition. Transcatheter embolization of the hepatic artery may be an attractive alternative to surgery for control of spontaneous rupture of the liver in preeclampsia. PMID- 2305088 TI - Percutaneous treatment of urine leaks in renal transplantation patients. AB - The data on post-renal transplantation urine leaks in 23 patients were retrospectively reviewed to assess the role of percutaneous urine-diverting procedures in their treatment. The leaks were confirmed by means of antegrade pyelography, and either a nephrostomy catheter or a nephroureteral stent was placed. Nephrostography was performed frequently to evaluate leak closure. Urinary diversion was continued for an average of 68 days. Leak closure was documented in 20 of 23 (87%) cases. In four patients, concomitant infection or multiorgan failure precluded adequate therapy. One patient developed a ureteral stricture after the urine-diverting procedure and required surgical correction. The results suggest that percutaneous urine-diverting procedures are a definitive treatment for post-renal transplantation urine leaks. PMID- 2305087 TI - Arteriogenic impotence: findings in 195 impotent men examined with selective internal pudendal angiography. Young Investigator's Award. AB - Selective internal pudendal angiography was performed in 195 men (average age, 35.4 years +/- 10.3) who were suspected of having arteriogenic impotence. In the majority of patients, disease was localized to the cavernosal arteries. A previous series that involved older patients had demonstrated significant disease in the hypogastric and internal pudendal arteries. When controlled for trauma, the data revealed no significant difference (X2 test, P greater than .10) in the distribution of hemodynamically significant penile arterial disease. However, in patients who had sustained major pelvic trauma, the common penile artery was frequently hemodynamically compromised. There is a great deal of variation in the origin of the internal pudendal artery. An accessory pudendal artery was demonstrated in 7% of the patients. If a selective internal pudendal artery injection fails to demonstrate the penile arterial anatomy, a less selective injection should be performed. Bilateral injections should always be performed, as unilateral arterial disease was present in 15% of the patients. PMID- 2305090 TI - Method to control spraying of high-velocity infected blood droplets during arterial catheterization. AB - Spurting of blood from standard arterial needles during guide-wire insertion can be controlled easily with a syringe and a simple needle inserted along the syringe plunger. With this method, blood droplets that may be infected with the hepatitis or human immunodeficiency virus will not come into contact with the head and neck of the angiographer or interventional radiologist. PMID- 2305089 TI - "High-flow" priapism: treatment with superselective transcatheter embolization. AB - Hemodynamically, most cases of priapism occur as a result of venous outflow obstruction producing engorgement of the corpora cavernosa. In a small number of patients, however, the cause is uncontrolled arterial inflow, often from direct arterial trauma. The authors report two cases of arterial or "high-flow" priapism that were successfully treated with selective transcatheter embolization with autologous clot. PMID- 2305091 TI - Self-contained, coaxial delivery system for intraarterial infusion of thrombolytic agents. AB - To facilitate continued direct intrathrombus infusion of a thrombolytic agent and yet minimize catheter exchanges and manipulations, the authors developed a simple, self-contained delivery system. It involves the use of supplies available in most angiographic suites. The system has been used in 44 patients; there have been no infectious complications, and it has been well tolerated by the patients. PMID- 2305092 TI - New guide wire for high-flow infusion. AB - A new open-ended guide wire with a large internal diameter was compared with two other open-ended guide-wire and catheter infusion systems. Simple experiments were performed to compare flow rates and ability to track. The larger internal diameter of the new wire allowed higher flow rates and accepted an 0.025-inch (0.64-mm) guide wire. The flexibility of the new infusion wire was shown to be equivalent to that of the catheter system. The authors conclude that the new wire has advantages in terms of flow rates and ability to track, compared with presently available infusion systems. PMID- 2305093 TI - Washington report: interventional radiology. PMID- 2305094 TI - Monitoring and evaluating the quality and appropriateness of angiographic/interventional radiologic procedures. AB - The safety and efficacy of invasive radiologic procedures should be monitored in all departments that include such activities. Assessing the data arising from such monitoring and taking the actions needed to improve quality and appropriateness of care are additional steps that must be taken to meet the expectations of the JCAHO. The SCVIR has distributed to its membership for comment a proposal for a model program for monitoring and evaluating angiographic/interventional procedures that, if adopted by a department, would help meet external accrediting reviews. The SCVIR also has under study a proposal to develop a national data base that would act as a repository of information on invasive radiologic procedures. By voluntarily participating in the program, departments would receive feedback that periodically documents performance and compares it with national norms established by all participants in the program. If the data base is sufficiently detailed, distinct advantages of collaborative research could result. Data related to comparative technology assessment, cost benefit analyses, and other derived information could then be made available to other physicians, the public, payers, and government agencies. The discipline of radiology would have a vehicle to influence and create national recommendations for health care policy decisions. PMID- 2305095 TI - Dieulafoy disease: arteriographic findings and treatment. AB - Dieulafoy disease is an unusual cause of massive and frequently fatal gastrointestinal tract hemorrhage that results from the erosion of a submucosal artery. Although the lesion has been found throughout the gastrointestinal tract, it most commonly occurs in the proximal stomach. Nine patients with this condition have been treated at the authors' institution during the past 5 years. The bleeding lesion was located before surgery with selective visceral arteriography in three patients. Rapid extravasation was demonstrated from an eroded but otherwise normal-appearing artery in all three cases. Hemorrhage was controlled successfully in one patient with selective embolization of the involved left gastric artery branch. The remaining eight patients were treated with surgical ligation. PMID- 2305096 TI - Dieulafoy disease: a real entity? PMID- 2305097 TI - Bleeding marginal ulcers: angiographic evaluation. AB - The authors reviewed angiograms of patients who had previously undergone gastrojejunostomy and who were suffering from gastrointestinal bleeding. In five patients the site of bleeding was a surgically or endoscopically proved marginal ulcer. Only two of these ulcers were supplied by jejunal branches of the superior mesenteric artery; three of the five were supplied by gastric branches of the celiac artery. Thus, in angiography of patients with bleeding from marginal ulcers, the celiac, as well as the superior mesenteric, artery may need to be investigated. PMID- 2305098 TI - Tube tamponade: potential pitfall in angiography of arterial hemorrhage associated with percutaneous drainage catheters. AB - Diagnostic angiography performed to search for a source of hemorrhage in three patients with percutaneous transhepatic biliary catheters and one patient with a percutaneous nephrostomy catheter was initially unrewarding when performed with the drainage catheter in place. In each patient, removal of the drainage catheter resulted in severe pulsatile hemorrhage from the parenchymal tract and allowed angiographic localization of the bleeding site. Temporary control of the hemorrhage was then obtained by inflating an angioplasty balloon within the tract. Transcatheter embolotherapy provided definitive control of bleeding in three patients. When initial angiographic evaluation for bleeding in patients with percutaneous biliary and nephrostomy catheters fails to depict a source, the study should be repeated immediately after removal of the drainage catheter. Because hemorrhage can be severe once tamponade is relieved, the drainage catheter should be withdrawn over a guide wire so that a tamponading catheter can be rapidly reinserted to control hemorrhage until more definitive therapy is undertaken. PMID- 2305100 TI - The cause of superior vena cava syndrome: diagnosis with percutaneous atherectomy. AB - The cause of superior vena cava syndrome (SVCS) in two patients was identified by means of endovascular biopsy of the superior vena cava (SVC) performed with a percutaneous atherectomy catheter. In both cases, the extracted tissues were neoplastic, therefore obviating additional invasive procedures. After a specific diagnosis was established, external-beam radiation therapy was used to treat the SVCS. The atherectomy catheter was used in conjunction with other percutaneous techniques, including balloon angioplasty and endovascular stenting of the SVC. PMID- 2305099 TI - Techniques for lower-limb angiography: a comparative study. AB - Three separate variables--volume of contrast material, site of contrast material injection, and arterial inflow occlusion--were tested in a prospective, randomized fashion in 52 patients to determine the best technique for lower-limb angiography. Twelve patients received 30 and 60 mL of contrast material injected at the level of the external iliac artery (EIA), 20 patients received 60 mL injected at the level of the EIA with and without inflow occlusion, and 20 patients received 120 mL injected at the level of the aortic bifurcation and 60 mL injected at the level of the EIA. A total of 104 angiograms were obtained, two in each patient. Two examiners reviewed all angiograms in a blinded fashion, initially as 104 separate studies for diagnostic adequacy (ie, the need for additional angiography) and then as 52 paired studies for direct comparison of the quality of arterial filling (ie, the best-appearing angiogram). The 60-mL studies were significantly better (P less than .001) in both categories when compared with both the 30- and the 120-mL studies. There was, however, no significant difference between the 60-mL studies with and without inflow occlusion. The authors conclude that the best screen-film lower-limb angiograms are obtained with large volumes (60 mL) of contrast material injected below the pelvic vessels (EIA). PMID- 2305101 TI - Physician's expert testimony for nurse. PMID- 2305102 TI - Nurses' "sudden death" testimony inadmissible. Case in point: Perez v. Hartmann (543 N.E. 2d 1023--IL (1989)). PMID- 2305103 TI - 4.5 million dollars judgment v. CRNA: damage cap applied. Case in point: Leiker by and through Leiker v. Gafford (778 P. 2d 823--KS (1989)). PMID- 2305104 TI - [The divided female--motherhood and public culture]. AB - The author compares "individual" motherhood, common in countries like Switzerland and the Federal Republic, with the "social" motherhood characteristic of a Mayan peasant culture in Yucatan. She discusses various psychoanalytic conceptions of motherhood, for instance, Freud's and Winnicott's. She argues that the ideological concept of the missing penis actually expresses the very real cultural deficiency of women. The retention of such ideological concepts prevents the actual conditions from being acknowledged in psychoanalytic theory. This, in turn, blocks the change in paradigm necessary for an adequate metatheoretical handling of gender differences. PMID- 2305105 TI - Preference for information and involvement, information seeking and emotional responses of women undergoing colposcopy. AB - The relationship of individual differences in preference for information and involvement, information-seeking behaviors, and emotional responses was examined in 36 women undergoing colposcopy, a stressful medical procedure. The findings revealed that individual differences in preference for information and behavioral involvement in health care influenced women's information seeking about colposcopy. Women who asked more questions during their clinic visits reported higher preferences for information. Women who sought an information sheet about colposcopy reported higher preference for behavioral involvement in their health care. The findings also revealed that information seeking was associated with the positive emotional response confidence but not with fear or anger/depression. PMID- 2305106 TI - Participation in alternative care: relationship to anxiety, depression, and hostility. AB - Women's psychological mood and its relationship to satisfaction with participatory perinatal care was examined using a two-group evaluation design of convenience samples (N = 99). Women entered the perinatal experience with similar degrees of anxiety, depression and hostility, but contrary to prediction, the type of perinatal experience, conventional or alternative, was not associated with their psychological mood. However, women in both groups reported less anxiety 2 to 3 days and 4 weeks after delivery than they reported having in general prior to delivery. Women who were more satisfied with care and their participation in care, regardless of whether they had an alternative or conventional perinatal experience, reported less anxiety and depression immediately post delivery. In 4 weeks, satisfaction and participation in care were still negatively related to anxiety. PMID- 2305107 TI - Temperament, behavior problems, and learning skills in very low birth weight preschoolers. AB - The relationship between temperament, behavior problems, and learning skill abilities in preschool children who were born with very low birth weight (VLBW) is described. Subjects were 37 4-year-olds who weighed less than 1,500 grams at birth, were appropriate for gestational age, and free from congenital anomalies (M birth weight = 1,201 grams). Data were gathered when the children were 48 months chronological age and analyzed using point biserial and Pearson product moment correlation, chi square, and MANOVA. Temperament characteristics of rhythmicity, intensity, and persistence were related to behavior problems and learning skill abilities. Mothers reported more children with behavior problems than expected in the general population. Children with four or more behavior problems had significantly lower skill achievement scores than children with fewer behavior problems. PMID- 2305109 TI - The dimensionality of the UCLA Loneliness Scale in early adolescents. AB - The dimensionality of the UCLA Loneliness Scale was assessed in 326 adolescents aged 12 to 14. Based on theoretical grounds, a one-factor solution was examined. The results lend limited support to the assertion that the instrument measures a single dimension of loneliness. Factor solutions ranging from three to five were unacceptable according to the methodological criteria used in this study. A two factor solution met the methodological criteria but the results were suggestive of a method artifact. This possibility was explored using a procedure that follows the logic of construct validation. The findings suggested that the instrument has two substantive dimensions. Continued support of the bidimensionality of the instrument would have implications for theory development regarding the phenomenon of loneliness. PMID- 2305108 TI - Patterns of functioning in families with a chronically ill parent: an exploratory study. AB - Findings from an assessment of the pattern of functioning of families with dependent children in which one parent was chronically ill are presented. The Moos Family Environment Scale scores of 67 chronically ill individuals and their spouses were subjected to cluster analysis procedures. Four clusters of families were identified and described: cohesive, moral-religious oriented, structured conflict, and unstructured conflict. Structured conflict families possessed lower socioeconomic status and perceived greater impact of illness than cohesive families. Cluster analysis proved particularly useful because it allowed consideration of how groups of families vary from each other, as well as how specific dimensions of family functioning may covary with one another within groups. PMID- 2305110 TI - Quality of reporting in diabetes patient education research: 1954-1986. AB - The quality of reported research representing a number of disciplines involved in diabetes patient education was investigated in this study. A rigorous literature search identified 47 studies reported between 1954 and 1986 that met inclusion criteria; 29 were published studies, 18 were unpublished. Quality of the research was measured by Duffy's Research Appraisal Checklist (RAC) and also by coding each study as to the number of threats to internal and external validity present. Overall quality as measured by the RAC ranged from 34 to 95 on a 100-point scale. A statistically significant relationship was found between publication date of the research report and quality, indicating improvement in quality during recent years. Quality of published versus unpublished research reports was not found to differ significantly. Recommendations for improving methodological rigor of future studies include: (a) the use of more rigorous designs, particularly those involving control groups such as randomized clinical trials; (b) reporting of more complete data in research reports; and (c) monitoring of the quality of future studies. PMID- 2305111 TI - Ethnic differences in physiological responses associated with the Valsalva maneuver. AB - Ethnic differences in cardiovascular indices at rest and across the Valsalva maneuver (VM) were studied in 30 Asian, 86 Caucasian, and 12 Black healthy men and women aged 30 to 55 years. Subjects simulated the VM by blowing into an aneroid pressure-gauge meter to 40 mmHg for 10 seconds. Resting systolic blood pressure (SBP) was significantly higher in Blacks than in Asians or Caucasians. During the strain phase of the VM, the fall in SBP from baseline was significantly greater in Asians and Blacks than in Caucasians. Further, Asians had the greatest overshoot of SBP above baseline. Although resting heart rate was significantly higher in Asians compared to Caucasians, there were no differences in heart rate responses to the VM. Reduction in carotid artery blood flow velocity during strain was significantly less in Blacks. We conclude that there are ethnic differences in cardiovascular indices at rest and across the VM. PMID- 2305112 TI - Inhibition by sodium citrate on 67Ga adsorption to various materials. AB - The adsorption of 67Ga to the inner surface of stainless steel, polyethylene and silicone tubings was studied. The three tubings remarkably adsorbed 67Ga in order of stainless steel, silicone and polyethylene tubing. Sodium citrate inhibited the adsorption of 67Ga in a dose-dependent manner. These phenomena were also observed in blood sampling via the catheter inserted into the external jugular vein. These results show that constant concentration of sodium citrate is necessary for the in vitro study of 67Ga in order to prevent the adsorption to the surface of experimental materials. PMID- 2305113 TI - Abnormal hepatobiliary clearance of 99mTc-N-(2,6 diethylphenylcarbamoylmethyl)iminodiacetic acid in the altered state of thyroid- by an analysis of deconvolution method. AB - Hepatobiliary clearance of 99mTc-EHIDA was investigated in cases with altered thyroid function by deconvolution method. The results indicated that mean hepatic transit time of all control subjects revealed less than 10 minutes. On the other hand, mean hepatic transit time of cases with altered thyroid function revealed prolonged more than 13 minutes. Cases especially showing an elevated serum concentration of TSH compared with normal range (4.6 microU/ml) had a tendency of a high incidence of markedly prolonged mean hepatic transit time. These results suggest that thyroid hormone may influence on the hepatic metabolism of hepatobiliary radiopharmaceuticals. This phenomenon also could partly explain the cause of liver dysfunction seen in subjects with altered states. PMID- 2305114 TI - [Experimental studies on peripheral nerve injuries caused by injection needles]. AB - Differences in neural damage due to different injection needles were investigated in vitro on sciatic nerve specimens of adult rabbits. METHODS. Three types of 22 gauge needles were tested: one typical, long-bevelled venous puncture needle; a short bevelled, typical nerve block needle; and a tapered, atraumatic spinal needle. Both sciatic nerves of 50 adult rabbits weighing from 2.5 to 3.0 kg were used for electrophysiological investigations on one side and fluorescence microscopy on the other. ELECTROPHYSIOLOGY. The nerve specimens were placed in an experimental chamber on silver-silver chloride electrodes that were aligned at a distance of 10 mm. Two electrodes at the distal ends of the nerve were used for stimulation by rectangular waves (6-10 v) of 0.01 ms duration. The compound action potential (CAP), its amplitude, and its latency were measured by monopolar recording from four additional electrodes (R1 to R4). Ten nerves were apportioned to each of five groups and the needles were perpendicularly pierced three times in the middle of the nerve trunk at the midpoint between recording sites R2 and R3. THE GROUPS. 1. Long-bevelled needle, the face of the bevel inserted rectangular to the nerve fibers; 2. long-bevelled needle, the face of the bevel parallel to the nerve fibers; 3. short-bevelled needle, the face of the bevel inserted rectangular to the nerve fibers; 4. short-bevelled needle, the face of the bevel parallel to the nerve fibers; 5. tapered, pencil-point needle pierced perpendicularly through the nerve trunk. The amplitude of the CAP was recorded before and after nerve injury from R1 to R4. FLUORESCENCE MICROSCOPY. According to the method described by Steinwall and Olsson, the other five groups of injured nerves were immersed in Evans blue albumin (EBA) and, after washing in saline solution, fixed in 5% formalin. The extent of nerve damage was evaluated by fluorescence microscopy of the glycerol-imbedded frozen sections (longitudinal and transverse). RESULTS. Electrophysiology. After injuring the area between R2 and R3 there was almost no change in the amplitude of the CAP at sites R1 and R2. The amplitude at R3 and R4 was reduced in comparison with the controls. This reduction was most marked in group 1 and very slight in group 5. The percentages of amplitude at R3 after injury compared with control values (mean +/- SD) were 42.2% +/- 22.0% in group 1; 60.9% +/- 18.2% in group 2; 51.0% +/- 22.3% in group 3; 71.0% +/- 18.0% in group 4; and 90.1% +/- 10.9% in group 5. Statistically significant differences were obtained between the tapered, atraumatic needle group and the other four groups (Fig. 3). Fluorescence microscopy. With the tapered injection needle there was the least leakage of EBA, which suggests the least damage to the perineurium, and almost no rupture or tearing of the nerve fibers was observed. In the short- and long-bevelled needles, the damage was reduced when the face of the bevel was inserted parallel to the fibers. PMID- 2305115 TI - [The significance of the sampling site in the determination of plasma levels of local anesthetics using 0.75% bupivacaine as an example]. AB - Knowledge of the actual concentrations of local anesthetic administered by various techniques is essential requisite when undesirable side effects and possible toxicity of a substance are to be evaluated. Therefore, numerous studies of plasma concentrations have been presented, which were carried out with the additional purpose of analyzing the kinetics of different local anesthetics with respect to limiting-value concentrations in the organism. Despite a sufficient degree of precision in the analysis of amide local anesthetics, it is uncertain whether the results of the different studies are comparable, because blood samples have been taken variously from peripheral veins, central veins or arteries. In the present study changes in bupivacaine concentrations were monitored by means of a standardized method consisting in simultaneous sampling of blood in peripheral veins, central veins and arteries. METHODS. Each of 12 patients undergoing orthopedic hip surgery received average 17 ml bupivacaine (0.75%) via peridural lumbar catheter. After the administration of bupivacaine, blood samples were taken simultaneously from peripheral veins, central veins and arteries at 1, 3, 5, 10, 15, 30, 45, 60, and 90 min after injection. Placement of an arterial cannula and central venous catheter was indicated in all patients (hip-joint revision arthroplasty). Quantitative analysis of bupivacaine concentration was carried out by means of high-pressure liquid chromatography (HPLC). All patients had given their informed consent. RESULTS. All patients showed a rapid increase in bupivacaine concentration in the central venous blood within the first few minutes after administration, the maximum being reached between 3 and 10 min after. A similar course was observed with arterial plasma concentrations; absolute values, however, were an average of 10-20% lower at 15 min following administration. Bupivacaine concentrations in peripheral veins rose more slowly and reached a maximum between 15 and 30 min. At 30 min after peridural application the concentration curves in blood from all three sites were similar. DISCUSSION. In earlier studies the influence of the site of blood sampling has often been underestimated. According to our results, central venous and arterial plasma concentrations correspond closely at all times following peridural application. The observed uniform differences in concentrations at the various sites of sampling can be explained by the fact that pulmonary uptake of local anesthetics causes the lower arterial levels. Especially in the early phase of resorption after administration of local anesthetics, the concentration in peripheral blood does not seem to be representative, because an equilibrium is not established between arterial and central venous blood until 30 min after administration at the earliest. In our opinion the peripheral venous concentrations are unreliable, particularly in the early phases, for the evaluation of unwanted effects or toxicity of local anesthetics, because the initial low values and the delayed increase in these could lead to a false sense of security. PMID- 2305116 TI - [Reply to the comments of K.H. Weis on the paper by P. Hoffman and A. Franz. Thoracic peridural anesthesia in childhood]. PMID- 2305118 TI - Scleroderma. PMID- 2305117 TI - [Elimination of the obturator reflex as a specific indication for dilute solutions of etidocaine. A study of the suitability of a local anesthetic for reflex elimination in the 3-in-1 block technic]. AB - Direct stimulation of the obturator nerve by the electroresectoscope during transurethral resection of tumors in lateral bladder regions is possible under regional or general anaesthesia without muscle relaxation. The resulting obturator reflex may lead to perforation of the bladder. Two different regional techniques can be used to interrupt the obturator reflex arc: (1) separate block of the obturator nerve; or (2) the "3-in-1 block" (Winnie). In the present study elimination of the obturator reflex was carried out by "3-in-1 block" with diluted solutions of etidocaine in 55 cases. Venous plasma levels of etidocaine were measured in 9 patients after application of etidocaine 0.5% (unilateral 30 ml and bilateral 60 ml). Samples were taken 10, 20, 30, 40, 60, and 120 min after the "3-in-1 block". RESULTS. The "3-in-1 block" with diluted etidocaine produced excellent motor block of the obturator nerve. Clinical side effects did not occur. Plasma peak levels reached 2.2 micrograms/ml; the protein binding rate was 85%-95%. DISCUSSION. Elimination of the obturator reflex is the only specific motor nerve block in anesthesia. Diluted etidocaine solutions seem to be adequate: irrespective the technique used for eliminating the reflex, diluted etidocaine produces a good effect and permits a dosage reduction compared with other local anesthetics. It is possible to block the obturator nerve bilaterally by "3-in-1 block" or unilaterally by "3-in-1 block" in combination with epidural analgesia within the recommended dose limits. PMID- 2305119 TI - Vision and the brain--the organization of the central visual system. New York, December 4-5, 1987. Proceedings. PMID- 2305120 TI - [Cigarette smoking and lung function]. PMID- 2305122 TI - [Epidemiology of lung cancer with special reference to cigarette smoking]. PMID- 2305121 TI - [Smoking and immunity allergy]. PMID- 2305124 TI - [Smoking and pulmonary circulation]. PMID- 2305123 TI - [Tobacco smoking and lung cancer--its role in carcinogenesis]. PMID- 2305125 TI - [Sex influence on the cardiac complication of ankylosing spondylitis--analysis of 95 cases of ankylosing spondylitis including our case]. AB - Ankylosing spondylitis is apparently rare among Japanese and it is known that this disease is commoner in males than in females. The male to female ratio among general ankylosing spondylitis is 4.5:1. The cardiac conduction abnormalities, aortic insufficiency and mitral insufficiency are sometimes associated with this disease. We analysed the influence of sex on the development of these cardiac complications using 95 reported cases of ankylosing spondylitis including our case. Among the ankylosing spondylitis patients who were accompanied with cardiac complication, 99% were male. This frequency is significantly high compared with that found in general ankylosing spondylitis (p less than 0.0001). The cardiac complication associated with this disease seems to be characteristic for males. This sex difference is useful for differential diagnosis from various diseases which accompany these cardiac complications. The mechanism of sex influence on the cardiac complication of ankylosing spondylitis was also discussed. PMID- 2305126 TI - [Different sensitivity of sinus node and atrioventricular node to adenosine triphosphate]. AB - We showed that higher concentration of adenosine 5'-triphosphate (ATP) was required to prolong the spontaneous cycle length of the sinus node (SN) than that required to prolong the spontaneous cycle length of the atrioventricular node (AVN). Spontaneously beating preparations of SN and AVN of rabbit (n = 8) were superfused with Tyrode solution containing 10(-8)-10(-3)M ATP, and action potential was recorded. The negative chronotropic action of ATP was dependent on the concentration. The required concentration of ATP to prolong spontaneous cycle length significantly (p less than 0.01) was 10(-5)M in SN and 10(-6)M in AVN, respectively. At concentrations higher than 10(-6)M, the degree of prolongation was greater in AVN than in SN (p less than 0.01). 10(-7)M dipyridamole enhanced this effect of ATP, while 10(-4)M theophylline reduced it. Action potential duration of 50% repolarization was not changed significantly in either SN or AVN at concentrations up to 10(-3)M. Maximum diastolic potential (MDP) was hyperpolarized from 10(-8)M to 10(-4) M. Hyperpolarization of MDP induced by ATP was greater in AVN than in SN but it was not statistically significant. MDP was depolarized by 10(-3) M ATP in both SN and AVN. The maximum velocity of depolarization was slightly larger in both SN and AVN as the concentration of ATP was increased in the perfusate. However, it was not statistically significant. 10(-3) M ATP decreased the maximum velocity of depolarization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305127 TI - [Valvular regurgitation in patients with complete heart block by color Doppler echocardiography]. AB - We studied valvular regurgitation (pulmonary, aortic, tricuspid and mitral regurgitation) in 30 patients with complete heart block by color Doppler echocardiography, pulse Doppler and continuous wave Doppler echocardiography. The prevalence rate of multivalvular regurgitation of these subjects was 83.3%. Regurgitation involving all four valves appeared in 30.0% of these patients. The prevalence rate of pulmonary, aortic, tricuspid and mitral regurgitation was 56.7%, 33.3%, 100%, and 76.7% respectively. Pulmonary regurgitation (PR) was observed in patients with complete heart block without pulmonary hypertension. PR velocity was slow and interrupted by atrial contraction. It might be possible to evaluate atrial pressure from the interruption of PR. Tricuspid regurgitation (TR) during systole was often present in patients with right ventricular endocardial pacing. Systolic TR was influenced by atrial contraction. When atrial contraction occurred during systole, TR was interrupted, or shortened. Diastolic TR and MR were easily detected by M mode color Doppler echocardiography. The diastolic TR and MR were of slow velocity and appeared 240-290 msec after P wave. These atypical valvular regurgitation in patients with complete heart block reflect of the inverse atrial-ventricular pressure gradient across the atrio ventricular valve. PMID- 2305128 TI - [Evaluation of antihypertensive therapy by ambulatory blood pressure monitoring and establishment of the level of antihypertensive goal on the circadian rhythm of blood pressure]. AB - We have developed a new method for the evaluation of antihypertensive therapy on the circadian rhythm of blood pressure and attempted to determine the indications for antihypertensive therapy and the level of antihypertensive goal. Blood pressures were measured for 24 hours by the use of ambulatory blood pressure monitoring using 630 (ABPM-630) in 50 normotensives, 50 untreated hypertensives and 50 hypertensives undertreatment with various antihypertensive drugs (110 males and 40 females, with a mean age of 53.4 +/- 13.3 yrs). Blood pressure profiles were prepared for determination of the hyperbaric and hypobaric indexes. According to the WHO's definitions for blood pressure, the hyperbaric index was defined as the area above 140 mmHg in systolic blood pressure or 90 mmHg in diastolic blood pressure, and the hypobaric index, as the area below 100 mmHg or 60 mmHg, respectively. The criteria of the hypobaric index was obtained from the mean basal blood pressure (the lowest blood pressure during sleep) of the 50 normotensives. The mean hyperbaric index of the 50 normotensives was 20.4 +/- 40.2/5.5 +/- 15.3 (systole/diastole) mmHg.hour/day and the mean hypobaric index, 12.2 +/- 22.5/9.0 +/- 24.0 mmHg.hour/day. The 50 untreated hypertensives showed a mean hyperbaric index of 281.8 +/- 197.0/156.0 +/- 126.1 mmHg.hour/day and a mean hypobaric index of 0.1 +/- 0.6/0.3 +/- 1.5 mmHg.hour/day. Comparison of the indexes before and after treatment with various antihypertensives showed that a decrease in the hyperbaric index without an increase in the hypobaric index was the most optimal reduction of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305129 TI - [A case of latent cardiac sarcoidosis in reference to differential diagnosis from giant cell myocarditis]. AB - We report a case of latent cardiac sarcoidosis in reference to differential diagnosis from giant cell myocarditis. A 68-year-old woman succumbed to subarachnoid hemorrhage and acute myocardial infarction within a period of 3 days. Autopsy revealed white fibrotic lesions in the lateral wall of the left ventricle and interventricular septum of the heart in addition to acute myocardial infarction of the anterior wall. Histology showed fibrotic granulomatous lesions with infiltration of lymphocytes and epithelioid cells. Many multinucleated giant cells of Langhans and foreign body types were scattered among these lesions. There was no lesion in the bilateral hilar lymph nodes, but typical epithelioid granuloma was noticed in the lymph node of the carina, liver, and spleen. So we concluded that the heart lesion was a case of cardiac sarcoidosis. Striation could not be seen in the multinucleated giant cells of the cardiac sarcoid lesion, and, using light microscopy, it seemed to us that these cells had no relation to the cardiac muscles. However, by immunohistochemistry (PAP method) some giant cells tested positive for myoglobin, and others tested positive for lysozyme. The fact that giant cells are not always derived from the cardiac muscle can't be used, as a criterion for the diagnosis of cardiac sarcoidosis. Giant cells in the lung and lymph nodes tested positive only for lysozyme. Hence, using only cardiac histology, it is difficult to make a differential diagnosis between cardiac sarcoidosis and giant cell myocarditis, especially in cases where there is multiple organ involvement. PMID- 2305130 TI - [A case of congenital sinus of Valsalva-right ventricule fistula]. AB - A 58-year-Old male was admitted to our hospital because of heart murmur. This heart murmur had been first noticed when the patient was 7 years old, but he had no other symptoms. Color Doppler echocardiography and aortography showed that there was no deformity in the sinus of the Valsalva or in the connection to the right ventricle. Data of cardiac catheterization revealed that the shunt rate was 57% and Qp/Qs was 2.35. He was diagnosed as having congenital fistula of the Valsalva sinus to the right ventricle and an operation was recommended. PMID- 2305132 TI - [Secundum atrial septal defect in two families]. AB - Two families having secundum atrial septal defect (ASD) were reported. In one family, a 31-year-old male and his 60-year-old mother had secundum ASD without PR prolongation. His 38-year-old brother was diagnosed as having ASD. His grandmother, who had died at the age of 51, was suspected of having congenital heart disease. From early childhood she was noticed to have heart murmur. It was suspected that this was a case of familial ASD without PR prolongation, because it was consistent with the dominant trait of the defect. In the other family, a 16-year-old female had secundum ASD and her 18-year-old brother was also suspected of having ASD. Her 25-year-old brother had been operated on for tetralogy of Fallot, and her sister had died of an unknown congenital heart disease. All of these family members had mental retardation. Her 22-year-old brother was suspected of having a congenital heart disease, because of heart murmur from his early childhood. The parents, who were blood relations (cousins), had neither heart disease nor mental retardation. The children of this family were considered to be cases of congenital heart disease with ASD, associated with mental retardation. It was also suspected that the cause of the defect was a deleterious autosomal recessive gene. PMID- 2305131 TI - [A case of bilateral coronary artery--pulmonary artery fistulas associated with mitral valve stenosis]. AB - A case was reported of bilateral coronary artery-pulmonary artery fistulas associated with mitral valve stenosis. A thirty seven year old female was admitted with the complaint of exertional dyspnea and palpitation, which had lasted for the 3 years previous to her admission to our hospital. Electrocardiogram showed sinus bradycardia and no ST-T changes, but exercise ECG showed significant ST depression after 6 min of exercise. The DDR (9 mm/sec) and mitral valve area (0.61 cm2) were shown by UCG examination to have decreased, and the pressure at half time (360 msec) was shown by Doppler UCG to be prolonged. On cardiac catheterization, coronary arteriography showed fistula from RCA to PA, and fistula from LCA to PA, but no occlusive lesions were demonstrated. P/S blood flow ratio was 1.09, and O2 saturation was stepped up 3% in PA. She was operated on and given open mitral commissurotomy and closure of the fistula opening, via the PA. After surgical repair, no abnormality was found by exercise ECG, and no fistulas were shown on coronary arteriography. PMID- 2305133 TI - Adult leukemia. PMID- 2305134 TI - Blood support for the myelosuppressed patient. PMID- 2305135 TI - [Fatal pulmonary hypertension in Sharp syndrome (M.C.T.D.) with pulmonary fibrosis]. AB - We have followed a case of Mixed Connective Tissue Disease (M.C.T.D.) during 5 years. A progressive pulmonary hypertension inducing cor pulmonary failure terminated in a fatal issue. The prognosis of M.C.T.D. previously considered good is sometimes more severe in spite of immunosuppressive therapy. PMID- 2305136 TI - [The treatment of arterial hypertension. A plea for personalized therapy]. AB - The authors write in favour of giving a personal touch to the antihypertensive treatment according to the clinical, biological and hemodynamic state of each hypertensive patient. They present a course of medicinal and non medicinal measures adapted to eleven kinds of hypertensive patients. Doing this, they bring out the privileged directions of a diuretic, a beta-blocker, an alpha-blocker, a central acting sympatholytic agent, a calcium channel blocker and a angiotensin converting enzyme inhibitor. PMID- 2305137 TI - [Metabolic disorders of essential trace elements related to rheumatic disorders]. AB - Trace elements are usually considered as "alternative" therapy. The present work is devoted to the analysis of the modifications in zinc, copper and selenium status in rheumatic diseases. The effect of the usual drug treatment is further studied as well as the therapeutic opportunities in "classic" medicine. PMID- 2305138 TI - [Endoscopic sclerosing of esophageal varices in the University Hospital Center: preliminary results]. PMID- 2305139 TI - [Kinetics of mucus]. PMID- 2305140 TI - [What is your diagnosis? Acanthoma fissuratum (Syn.: granuloma fissuratum)]. PMID- 2305141 TI - [A case from practice (160). Syndrome X]. PMID- 2305142 TI - [Malignant lymphoma: a study of an outpatient cohort]. AB - Data from 168 patients with malignant lymphoma were collected. 57 had Hodgkin's disease, 76 suffered from non Hodgkin's lymphoma and 35 presented with chronic lymphocytic leukemia. All patients were treated between January 1980 and December 1986 at the medical policlinic of the university of Zurich either as in- or outpatients. Presentation at the time of diagnosis, therapeutic regimen and treatment success as well as prognostic features of disease were evaluated. Overall the therapeutic results in this patient cohort were good and comparable with the results of large prospective studies. Complete remission rate (CRR) was 91% and overall survival rate (OSR) after 5 years was 72% for Hodgkin's disease. In Non Hodgkin's lymphoma of low malignancy OSR was 60% after 5 years and 39% in NHL of intermediate or high malignancy. In NHL CRR varied according to histologic subtype. In Hodgkin's disease staging according to the Ann Arbor classification and extranodal involvement including the spleen proved meaningful for prognosis. In NHL the international working formulation (IWF) was a useful prognostic tool. Anemias, higher age and relapses carried a poorer prognosis whereas induction of remission was a favorable prognostic sign. For chronic lymphocytic leukemia staging according to Binet was found a useful prognostic criterion. PMID- 2305143 TI - [Weight loss, fever, dyspnea]. AB - A 41-year-old homosexual man complained about weight loss of 14 kg over a period of 6 months. He developed exertional dyspnea and fever up to 39.6 degrees C. The ESR was elevated and the fraction of immature neutrophils increased. Penicillin was administered with no effect, chest X-ray showed basal pulmonary infiltrates, P. carinii was found in bronchioalveolar fluid. HIV-serology was positive. Sulfamethoxazole/trimethoprim (1600/320 mg daily) and 100 mg of prednisolone/die led to reduction of fever. Prevention of P. carinii pneumonia relapse is currently underway with bi-weekly inhalation of pentamidine-isethionate aerosol. PMID- 2305144 TI - [A case from practice (161). Asymptomatic hematuria of obscure origin]. PMID- 2305145 TI - [What is your diagnosis? Large hiatal hernia (mixed type) with ulcerative reflux esophagitis]. PMID- 2305146 TI - [Humidifier lung as occupational disease]. PMID- 2305147 TI - [What is your diagnosis? Gouty arthropathy (arthritis urica)]. PMID- 2305148 TI - [Will the baby get AIDS? A newer test will provide the answer]. PMID- 2305149 TI - [What is your diagnosis? Phlebothrombotic total obstruction of the deep leg veins with involvement of the great saphenous and common iliac veins]. PMID- 2305150 TI - [Practical questions concerning cataract surgery]. PMID- 2305151 TI - [Harmony in dying]. AB - Dying and death have scarcely before our time preoccupied so many. Some even seem to thrive from thanatology. Do we physicians however consecrate patience and time to the dying of our next or our patients? Did we learn in medical school or with our patients to assist a dying person? Did we search for answers to death and dying by asking philosophers, physicians or musicians? Can we follow their reasoning in profit for our patients or for ourselves? Harmony in death can possibly be found in a harmonious life in our splendid and humane profession. Modest personal experience enriched by reflections tries imperfectly to bring harmony as hope to our dying. PMID- 2305152 TI - [A case from practice (162). Florid acromegaly with hypophyseal adenoma with supra- and parasellar involvement, arterial hypertension and status following radioisotope therapy for toxic nodular goiter in 1987]. PMID- 2305153 TI - [The 7 truths of Jacobs or "the psychotic order of things"]. PMID- 2305154 TI - [Malevoz' day hospital--a tool for rehabilitation?]. PMID- 2305155 TI - [4 cases of fits of delirium following pilgrimages or spiritual retreats]. PMID- 2305156 TI - [New peregrinations of the psychotic patient]. PMID- 2305157 TI - [The nurse in psychiatry and in public health in an ambulatory psychiatric service]. PMID- 2305158 TI - [Quality of life and chronic psychotic disorders. Study of 50 cases]. PMID- 2305159 TI - [Observations on the collaboration between the Psychosocial Service and the Cantonal Office of Minors derived from common situations]. PMID- 2305160 TI - [The demand for intervention in the home]. PMID- 2305162 TI - [Post-traumatic stress. Development of a concept and current therapeutic possibilities]. PMID- 2305161 TI - [Open door policy with a systematic profile]. PMID- 2305163 TI - [Psychiatric manifestations of HIV infection]. PMID- 2305164 TI - [Viewpoint. Observations about parallel medicine]. PMID- 2305165 TI - [Advisability of surgery in persons older than 80 years (and its outcome)]. PMID- 2305166 TI - Sleep-onset insomniacs have delayed temperature rhythms. AB - It was predicted from free running and ultradian cycle studies that sleep-onset insomniacs would have endogenous circadian rhythms that were phase delayed compared to good sleepers. Thirteen sleep-onset insomniacs and nine good sleepers were selected to differ only in their sleep-onset latencies as confirmed by polysomnography. their rectal temperatures were measured over a 26-h constant routine and analyzed with best-fit Fourier curves including 24-h fundamental and 12-h harmonic components. The temperature rhythm markers of the insomniacs' rhythms were approximately 2.5 h later than the respective phases of the good sleepers. The usual bedtimes of the insomniacs fell within the "wake maintenance zone" of their delayed temperature rhythm. The good sleepers had typical bedtimes several hours after their "wake maintenance zone" and closer to their body temperature minimum. It was suggested that manipulations to phase advance the insomniacs' rhythms would reduce their sleep-onset latencies. It was also predicted that early morning insomnia results from phase advanced circadian rhythms and that sleep maintenance insomnia results from an abnormal phase relationship between the 24-h temperature rhythm and 12-h sleep-alert rhythm. PMID- 2305167 TI - Vitamin B12 treatment for sleep-wake rhythm disorders. AB - Vitamin B12 (VB12) was administered to two patients suffering for many years from different sleep-wake rhythm disorders. One patient was a 15-year-old blind girl suffering from a free-running sleep-wake rhythm (hypernychthemeral syndrome) with a period of about 25 h. In spite of repeated trials to entrain her sleep-wake cycle to the environmental 24-h rhythm, her free-running rhythm persisted for about 13 years. When she was 14 years old, administration of VB12 per os was started at the daily dose of 1.5 mg t.i.d. Shortly thereafter, her sleep-wake rhythm was entrained to the environmental 24-h rhythm, and her 24-h sleep-wake rhythm was maintained while she was on the medication. Within 2 months of the withholding of VB12, her free-running sleep-wake rhythm reappeared. The VB12 level in the serum was within the normal range both before and after treatment. The other patient was a 55-year-old man suffering from delayed sleep phase syndrome since 18 years of age. After administration of VB12 at the daily doses of 1.5 mg, his sleep-wake rhythm disorder was improved. The good therapeutic effect lasted for more than 6 months while he was on the medication. PMID- 2305168 TI - Tests of memory in narcoleptics. AB - This study attempted to evaluate the validity of self-reports of memory deficits in narcoleptics by comparing the scores of these patients with the scores of matched control subjects on standardized tests of memory function. After completing a short interview designed to elicit qualitative information about memory difficulties, 30 narcoleptic subjects and 30 control subjects completed the Wechsler Memory Scale (WMS), Rey-Auditory Verbal Learning Test, the Rey Complex Figure Test, Strub and Black's List of Letters, and the Symbol Digits Modalities Test (SDMT). In addition, the Profile of Mood States (POMS) was used to detect variation in performance due to anxiety or fatigue. Continuous polygraphic recordings were obtained during the testing to detect any changes in alertness. Subjects with narcolepsy experienced more difficulty in maintaining attention than control subjects, as evidenced by significantly more perseveration errors (p less than or equal to 0.01) on Strub and Black's List of Letters. Despite differences in their ability to sustain attention, there were no significant differences between narcoleptic and control subjects on measures of concentration (Digit Span from the WMS, and the SDMT). Furthermore, there was no objective evidence of memory impairment when the scores of narcoleptic and control subjects were compared on standardized tests of immediate and delayed recall, as well as on tests of verbal and visual memory. PMID- 2305169 TI - Diabetes, erectile dysfunction, and sleep-related erections. AB - Sleep-related erections were assessed in conjunction with polysomnography in 100 diabetic and 400 nondiabetic men with complaints of erectile problems. We also measured bulbocavernosus reflex latency, heart rate response to deep breathing, postural-related blood pressure changes, penile arterial sufficiency, and brachial blood pressures. To investigate the relationship between diabetes and erectile capacity, the results obtained from men with and without diabetes were compared. Men with diabetes had fewer sleep-related erections, less tumescence time, diminished penile circumference increase, and lower penile rigidity than nondiabetic men. These diabetes-related differences were found regardless of the maximum penile rigidity observed. The diabetic group had less heart rate response to deep breathing and lower penile blood pressures than the nondiabetic group, but only among men with maximum penile rigidity less than 500 g. These data indicate that both neurological and vascular mechanisms are involved to a greater degree in organic diabetic impotence than in the organic erectile dysfunction that occurs in nondiabetic men. Finally, the pattern of lower values for measures of nocturnal tumescence among diabetic men, compared to nondiabetic men, occurred in all age groups, except the oldest. Among impotent men, age 65 years or older, no difference was found between men with and without diabetes. This suggests that diabetes may foreshadow some of the age-related pathophysiological processes associated with erectile dysfunction. PMID- 2305170 TI - Asymmetrical auditory probe evoked potentials during REM and NREM sleep. AB - Two experiments were conducted to evaluate interhemispheric differences in late auditory evoked potentials (AEPs) during rapid-eye-movement (REM), Stage 2, and Stage 4 sleep. In the first study, 1,000-Hz stimuli [80 db (SPL)] were presented binaurally at a rate of 1/1.1 s. Analyses of variance were computed on the absolute difference in the amplitude of right and left evoked responses. N1 AEPs were significantly more asymmetrical in Stage 4 sleep compared to either REM or Stage 2 sleep. A second study was conducted with a wider topographical electrode distribution. This study used both a long and a short interstimulus interval with 500-Hz 80-db SPL tone pips. The absolute difference in the amplitude of right and left AEPs was compared across sleep stage. Asymmetries were larger in Stage 4 sleep than in either REM or Stage 2. Examination of these data indicated relative hemispheric balance in REM and Stage 2 sleep with largest asymmetries in Stage 4. The results do not support the view that REM and non-REM sleep stages are associated with differential activation of the two cerebral hemispheres. Rather, they suggest that the sleep cycle is characterized by variations in the degree of asymmetry. Asymmetries in Stage 4 sleep were not consistently in favor of the left hemisphere. PMID- 2305171 TI - Postsurgical evaluation of uvulopalatopharyngoplasty: two case reports. AB - Uvulopalatopharyngoplasty (UPPP) has become a widely practiced procedure for the treatment of snoring and obstructive sleep apnea. Surgical outcome with UPPP has heretofore been assessed by investigators using the number of apneas per hour of sleep (apnea index) as the sole or primary criterion. We present two cases in which UPPP outcome was inadequately represented by the apnea index. It is suggested that the apnea/hypopnea index, extent of oxygen desaturations, degree of sleep fragmentation, level of daytime somnolence, interaction between respiratory function and sleep position and stages, and degree of respiratory strain be considered in the postsurgical evaluation. PMID- 2305172 TI - Pathophysiology of gastrointestinal infections: the role of bismuth subsalicylate. Scottsdale, Arizona, 11-14 February 1988. Proceedings. PMID- 2305173 TI - Antisecretory and antiinflammatory properties of bismuth subsalicylate. AB - The antisecretory properties of Pepto-Bismol (PB) and its active ingredient, bismuth subsalicylate (BSS), were studied in ligated (rabbit and pig) and unligated (rat) intestinal-segment models. When PB was administered to segments before intestinal inoculation with heat-labile (LT) Escherichia coli or Vibrio cholerae enterotoxins, the inhibition of fluid accumulation was 74%-94% and 60% 91%, respectively. In the pig, the percentages of inhibition by PB of fluid accumulation produced by organisms or toxins were 69% for E. coli P57 producing heat-stable enterotoxin (ST), 89%-95% for E. coli P155 producing ST and LT, 52% for ST alone, 95% for LT alone, and 73% for ST and LT. When PB was administered to the pig immediately after inoculation with E. coli P57, E. coli P155, ST alone, LT alone, or ST and LT, the percentages of inhibition of fluid accumulation were 76%, 80%, 56%, 97%, and 69%, respectively. However, in the rabbit and rat, PB failed to inhibit fluid accumulation when it was administered 5-60 minutes after inoculation of cholera or E. coli LT enterotoxins. In the rabbit the combination of BSS and the vehicle of PB was synergistic in preventing the fluid accumulation normally produced by cholera toxin. Finally, when PB or BSS was administered 30 minutes before intestinal inoculation with arachidonic acid in a rat model of inflammatory diarrhea, the percentages of inhibition of fluid accumulation ranged, in a dose-responsive fashion, from 16% to 113% for PB and from 25% to 111% for BSS. PMID- 2305174 TI - Effect of bismuth subsalicylate on fecal microflora. AB - Several studies have documented the efficacy of bismuth subsalicylate (BSS) for the prophylaxis and treatment of bacterial diarrhea. It is not known what effect, if any, BSS has on the normal bowel flora. We quantitated the fecal flora in healthy volunteers before and after they took BSS. In the first group, 8 ounces of BSS was given on two successive days. In the second group, a standard oral intestinal lavage preparation (GoLYTELY) was used to clean the colon and then 8 ounces of BSS was given during a 4-hour period. There were no changes in total microbial counts or in counts of individual groups such as enteric bacteria, Pseudomonas, Staphylococcus, Bacteroides, or Clostridium difficile. On day 2 the yeast counts rose 2.4 log10 colony-forming units/g in the group taking 16 ounces of BSS but did not increase in the group taking 8 ounces of BSS plus GoLYTELY. The counts returned to pretreatment levels by day 7. These results show that a 1- or 2-day course of BSS, even with an oral intestinal lavage preparation, did not have significant effects on the normal microbial populations in the fecal microflora. PMID- 2305176 TI - Effect of bismuth subsalicylate on chronic diarrhea in childhood: a preliminary report. AB - Stools collected from 39 infants and children with chronic nonspecific diarrhea and from 10 age-matched controls were examined for bile acid content with use of gas-liquid chromatography. Values were correlated with stool color. Mean concentration of bile acids in green stools (7.7 +/- 1.52 mg/g dry weight) was significantly higher than that in brown stools (3.76 +/- 0.7 mg/g dry weight) and in control stools (1.42 +/- 0.35 mg/g dry weight). In patients with green diarrhea, treatments with cholestyramine and bismuth subsalicylate (Pepto-Bismol) were equally effective in decreasing stool frequency, with the latter being more effective in decreasing water content. Patients with brown stools had an insignificant response to therapy. PMID- 2305175 TI - In vitro and in vivo effects of three bismuth compounds on fermentation by colonic bacteria. AB - Three bismuth compounds (tripotassium dicitrate bismuthate, bismuth subsalicylate, and bismuth subnitrate) were tested in vitro and in vivo for their effect on fermentation by colonic bacteria. The studies in vitro were done with use of a technique designed to determine the effect of each one of the bismuth compounds on the fermentation of several stool samples that had been mixed with lactose as additional fermentable substrate (fermentation of lactose-enriched stools, FLES). The three bismuth compounds reduced FLES significantly in 47 (81%) of 58 of the stool samples used to test their effect. Bismuth subsalicylate, which reduced FLES in 10 of 10 stool samples, showed the greatest reduction (mean reduction, 74%; P less than .0001). The in vivo studies, done in six flatulent patients, showed significant reduction (P less than .01) of colonic fermentation of ingested raffinose by oral bismuth subnitrate given for 8 days. PMID- 2305177 TI - Effect of bismuth subsalicylate on Clostridium difficile colitis in hamsters. AB - The therapeutic effect of bismuth subsalicylate (BSS, Pepto-Bismol) in Clostridium difficile colitis was studied in golden Syrian hamsters. C. difficile was fed to the hamsters by orogastric intubation 2-3 days after their arrival. Clindamycin (1.5 mg per animal) was given intraperitoneally 4 days later. Twenty four hours after challenge with clindamycin, animals were given BSS at dosages of 5, 10, and 15 mg twice daily for 5 days by orogastric intubation. Controls included untreated animals and those given 5 mg of vancomycin once daily by intubation. Delay in the time of death was observed in all BSS-treated animals and was statistically significant on days 4-6 in those receiving 15 mg twice daily. Vancomycin produced a greater delay in death than did BSS. Our study suggests that BSS at a dosage of 15 mg twice daily has some therapeutic effect on C. difficile colitis in hamsters. PMID- 2305178 TI - In vitro antibacterial activity of bismuth subsalicylate. AB - This study was undertaken to determine the in vitro activity of bismuth subsalicylate (BSS) and sodium salicylate (SS) against various groups of pathogenic bacteria. BSS had the greatest activity against Clostridium difficile, which had a minimal inhibitory concentration for 90% of the strains (MIC90) of 128 micrograms/mL. The Bacteroides fragilis group also had a relatively low MIC90 of 512 micrograms/mL. BSS had the least activity against Pseudomonas (MIC90, 6,144 micrograms/mL). SS was as active as BSS against aerobic bacteria but was less active against anaerobic bacteria. The MIC90 values of SS for C. difficile and the B. fragilis group were greater than 8,192 and 4,096 micrograms/mL, respectively. This study demonstrates that BSS has antibacterial activity in vitro at levels that should be achievable in the gastrointestinal tract. PMID- 2305179 TI - International Symposium on Anaerobic Bacteria and Bacterial Infections. Monte Carlo, Monaco, 25-28 September 1988. Proceedings. PMID- 2305180 TI - Evolution of antimicrobial susceptibility in isolates of the Bacteroides fragilis group in Spain. AB - The species included in the Bacteroides fragilis group are the most frequent nontoxigenic anaerobic bacteria pathogenic to humans. The emergence and increase of resistance to antibiotics among this group make surveillance and state-of-the art knowledge important. We studied the evolution of resistance to antibiotics in B. fragilis group organisms isolated at the University Clinical Hospital at Salamanca, Spain, from 1975 to 1987. No resistance to imipenem, chloramphenicol, or metronidazole was detected. The frequency of resistance to clindamycin was in the range of 6%-7%. Resistance to moxalactam, cefoxitin, mezlocillin, and piperacillin has increased steadily and is currently approximately 20%-25%. PMID- 2305181 TI - Anaerobic bacteria and bacterial infections: perspectives on treatment and resistance in Italy. AB - Results of laboratory tests of 2,000 samples obtained from 1984 to 1987 from patients with suspected anaerobic infections and the clinical experience of these patients are reported. Of these samples, 395 were positive for anaerobes; 36.5% of these 395 samples contained single organisms, and 63.5% contained a mixture of anaerobes and aerobes. Abdominal infections were the infections most frequently caused by anaerobes. The Bacteroides fragilis group and strains of Peptostreptococcus were the microorganisms most frequently isolated. In addition, 300 anaerobes isolated from clinical samples at three Italian hospitals were tested for susceptibility to 10 antibiotics (aztreonam, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, clindamycin, imipenem, metronidazole, penicillin, and piperacillin). Imipenem and metronidazole proved to be the most active agents, with low and similar values for the 50% and 90% minimal inhibitory concentrations (MICs). No microorganism showed resistance to these agents. After imipenem and metronidazole, clindamycin was the most effective agent tested. All other antibiotics tested showed elevated MICs against Bacteroides species and Clostridium difficile. In Italy, cefoxitin still maintains satisfactory activity against the majority of anaerobes tested. PMID- 2305183 TI - Development and evaluation of the spiral gradient endpoint method for susceptibility testing of anaerobic gram-negative bacilli. AB - The spiral gradient endpoint (SGE) method for antimicrobial susceptibility testing was evaluated as an alternative agar-dilution procedure that would require less time and materials than the reference standard agar-dilution (SAD) susceptibility test for anaerobic bacteria. For the SGE test a spiral plater produces a drug concentration gradient equivalent to up to eight twofold dilutions in a single agar plate. Bacteria are streaked in radial lines across this gradient, and the drug concentration at the endpoint location where growth ceases can be calculated. Early results demonstrated the need to develop a standardized procedure, various technical improvements, and revised SGE formulas that correct for drug diffusion in calculating endpoint concentrations for tests on aerobes and anaerobes. The revised SGE method demonstrated an overall 90.7% agreement (within +/- 1 twofold dilution) of the minimal inhibitory concentrations with those determined by the SAD method tested in parallel for 161 strains of a wide variety of anaerobic gram-negative bacilli and eight antimicrobial agents. The reproducibility, sensitivity, and significantly increased efficiency warrant further evaluation of the revised SGE method. PMID- 2305182 TI - Capnophilic and anaerobic bacteremia in neutropenic patients: an oral source. AB - The currently accepted empiric antibiotic therapy for bacterial infections in neutropenic patients may not cover the possibility of capnophilic and anaerobic bacteremia. Many of these infections develop in patients with severe mucositis or periodontitis, and the type of organisms recovered also suggests an oral source of infection. We present two cases of bacteremia in neutropenic patients who had been empirically treated with ceftazidime and piperacillin plus amikacin. In the first case a beta-lactamase-producing strain of Capnocytophaga ochracea was isolated; in the second case bacteremia was due to a mixture of Leptotrichia buccalis and Fusobacterium nucleatum. These observations emphasize the necessity for a reevaluation of the possible use of antimicrobial agents active against beta-lactamase-producing capnophilic organisms and anaerobic bacteria during empiric therapy in neutropenic patients with an oral source of infection. PMID- 2305184 TI - [Epidemiology and prevention of echinococcosis in France]. AB - Echinococcosis is a cosmopolitan parasitic disease caused by the larvae of two tapeworms: Echinococcus granulosus responsible for unilocular hydatidosis, and Echinococcus multilocularis responsible for alveolar hydatid disease. In both cases man is infected by ingesting eggs of these tapeworms belonging to the genus Cestoda. In France, the only animal that acts as definitive host and transmits the unilocular type of hydatid disease is the dog, while the alveolar type is transmitted by dogs, foxes and cats. Carnivorous pet animals must be taken into account in the prevention of echinococcosis, whether their role is direct or indirect (fouling plants). PMID- 2305185 TI - [Biological diagnosis of echinococcosis]. AB - The authors review the laboratory techniques used for diagnosis of echinococcosis (IFL, IHA, IEP, ES, ELISA) with emphasis on the value and standardization of the antigens utilized. The specificity of these tests makes it possible to differentiate hydatidosis from alveolar hydatid disease. PMID- 2305186 TI - [Hepatic alveolar echinococcosis: diagnosis and treatment]. AB - Alveolar echinococcosis is a parasitic disease which is relatively rare in humans. It almost exclusively affects patients of rural origin living in enzootic regions (Eastern France, Auvergne) and most lesions are in the liver. Several anatomico-clinical forms have been described; the most frequent is the multilocular form, but the disease may consist of one single cyst or abscess. The liver structure is always deeply altered, with compression, inflammation or superinfection. Jaundice, liver enlargement, abdominal pain or signs of secondary localizations are manifestations that lead to the discovery of hepatic alveolar echinococcosis. The anatomical features of the lesions are demonstrated by ultrasounds and computerized tomography. The main differential diagnosis is tumoral pathology of the liver. In most cases the diagnosis of echinococcosis is confirmed by serological tests, although needle or even surgical biopsy might be necessary. Diagnosed at an early stage, alveolar echinococcosis can be amenable to surgical treatment (hepatectomy), and liver transplantation may even be performed. Medical treatment with benzimidazoles seems to be promising. PMID- 2305187 TI - [Extrahepatic echinococcosis: diagnosis and treatment]. AB - Following a review of the diagnostic, evolutive and therapeutic aspects of pulmonary echinococcosis, which is the most frequent hydatid disease after the hepatic one, the authors develop the problems raised by echinococcosis affecting the heart, kidneys, bones and spleen. PMID- 2305188 TI - [Epidemiology and prevention of distomatosis in France]. AB - Only the large liver fluke Fasciola hepatica is frequently encountered in France. The small fluke is exceptional, owing to its mode of transmission. Opithorchiasis is observed among refugees from South-East Asia. The prevention of all types of distomatosis rests on food control. PMID- 2305189 TI - [Distomatosis: diagnosis and treatment]. AB - Distomatosis caused by Fasciola hepatica is fairly common in France. It is due to the ingestion of contaminated watercress or wild dandelions. Fever is frequent. Jaundice and liver pain are inconstant. The disease is often revealed by an isolated eosinophilia. Ultrasonography and/or computerized tomography are useful to evaluate the hepatic lesions. The diagnosis is confirmed by the finding of eggs in the stools or by serological tests. Numerous other flukes may infect people living overseas and particularly in South-East Asia. Clonorchis sinensis and other Opisthorchidae are responsible for distomatosis of the liver and digestive tract. Several types of intestinal distomatosis may also be acquired. Paragonimiasis (a pulmonary fluke) is particularly frequent in that part of the world. The diagnosis rests on the finding of eggs in the stools (digestive tract distomatosis) or in the airways (paragonimiasis) or on serological tests. The prognosis has been improved by treatment with praziquantel, a drug which in most cases stops the development of the disease within a few days. PMID- 2305190 TI - [Corticotherapy of Crohn's disease]. PMID- 2305191 TI - [Thoughts on the current evolution of the French medical language]. PMID- 2305192 TI - [Role of drug assays in the treatment of epileptic patients]. AB - Drug assays play an important role in the control of antiepileptic treatment because the relationship between the serum concentration of an active drug and its therapeutic effects and side-effects is closer than between dose and effect. Bioavailability, protein binding and drug elimination are subject to inter- and intraindividual variations. However, it is important to remember that the optimal therapeutic ranges reported for serum levels are only a guideline to drug therapy. It is the patient who must be treated and not the serum level. PMID- 2305193 TI - [Treatment of salmonelloses]. PMID- 2305194 TI - [How to recognize the psychogenic character of impotence?]. PMID- 2305195 TI - [Controversy: the role of Helicobacter pilori in gastroduodenal pathology]. PMID- 2305197 TI - [Responsibilities in using expert systems in medical decision-making]. PMID- 2305196 TI - [The role of Helicobacter pilori: reasons to believe it]. PMID- 2305198 TI - [Cyst of the ovary. Diagnosis, course and prognosis, principles of treatment]. PMID- 2305199 TI - [Cancer of the ovary. Diagnosis, course and prognosis]. PMID- 2305200 TI - [Interactions of chronic diseases and work: cardiovascular diseases]. PMID- 2305201 TI - [Dislocation of the ankle joint. Diagnosis, course and prognosis, principles of treatment]. PMID- 2305202 TI - [Cancer of the larynx and the hypopharynx. Epidemiology, diagnosis, treatment]. PMID- 2305203 TI - Survival after liver transplantation of patients with primary biliary cirrhosis in the Nordic countries. Comparison with expected survival in another series of transplantations and in an international trial of medical treatment. AB - Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery. PMID- 2305204 TI - Action of neurotensin on meal-stimulated gastric acid secretion in the dog. AB - In six to nine mongrel dogs the effect of graded doses of intravenous neurotensin (188, 375, 750, and 1500 pmol/kg h) on acid secretion basally or stimulated by distention (by isotonic glucose), peptone (0.5, 1, and 4 g%), and pentagastrin was studied. Neurotensin did not affect acid secretion basally, stimulated by distention, or the maximal peptone dose. However, when submaximal doses (0.5 and 1 g%) of peptone were instilled in the stomach, neurotensin stimulated the secretory response to intragastric peptone. This effect was observed in doses of intravenous neurotensin which mimicked circulating neurotensin concentrations after a standard test meal. Thus, neurotensin could be considered a physiologic stimulant of acid secretion when protein is present in the stomach. The mechanism for this action of neurotensin is unknown but could be partly explained by an enhanced release of gastrin. The potentiating effect of neurotensin on peptone stimulated acid secretion could play a major role in gastric secretory function of the dog. PMID- 2305205 TI - Effect of intraduodenal bile and Na- taurodeoxycholate on exocrine pancreatic secretion and on plasma levels of secretin, pancreatic polypeptide, and gastrin in man. AB - The effect of intraduodenally administered cattle bile (CB) and Na taurodeoxycholate (TDC) on basal pancreatic secretion and plasma levels of secretin, pancreatic polypeptide (PP), and gastrin were investigated on two separate days in 10 fasting volunteers. Doses of 2-6 g CB and 200-600 mg TDC were given intraduodenally at 65-min intervals. Volume, bicarbonate, lipase, trypsin, amylase, and bilirubin were measured in 10-min fractions of duodenal juice, and GI peptides determined by radioimmunoassay. CB and TDC enhanced significantly and dose-dependently volume, bicarbonate and enzyme secretion, and plasma secretin and PP levels. In contrast, plasma gastrin showed only a marginal increase. We conclude that the hydrokinetic effect of intraduodenal CB and TDC is at least partially mediated by secretin. Gastrin could be ruled out as a mediator of the ecbolic effect, whereas other GI peptides, primarily CCK, and/or neural mechanisms must be considered possible mediators. Both pathways may also play a role in the PP release observed. PMID- 2305206 TI - The role of mucosal prostaglandin levels in healing of water immersion-induced gastric ulcers in rats. AB - This study was designed to clarify the recovery time course of water immersion stress ulcers. Rats were divided into two groups: the control group and the cetraxate group. In the cetraxate group, 6 h after water immersion stress, cetraxate (300 mg/kg) was administered intragastrically twice a day until the end of the experiment. Ulcer indices were observed immediately, 1, 3, 7, 14, and 21 days after water immersion stress in each group. Changes in gastric mucosal prostaglandin (PG) levels were measured by means of high-performance liquid chromatography. In the control group ulcer healing was not observed within 1 day after stress. Gastric lesions had decreased significantly after 3 days, but 21 days were required for total healing. Accelerated ulcer healing was observed in the cetraxate group. Four kinds of PGs were detected in gastric mucosa: 6-keto PGF1 alpha, PGF2 alpha, PGE2, and PGD2. Recovery of PG levels differed from each other. Fourteen days were required for full recovery of PGD2 and 6-keto-PGF1 alpha. In contrast, 7 days were required for recovery of PGF2 alpha and PGE2. Cetraxate accelerated the recovery of gastric mucosal PGD2 and 6-keto-PGF1 alpha levels, especially the former. These results suggest that PGs, especially PGD2, are linked with the healing processes of stress ulcers. PMID- 2305207 TI - Attenuation of gastric sham feeding response during reflex sympathetic activation in man. AB - In six human volunteers we studied the effects of hypovolemia on the secretory activity of the gastric mucosa. The secretion of acid and HCO3 from the stomach was calculated from continuous measurements of pH and Pco2 in gastric effluent. Gastric secretion was stimulated by sham feeding (SF), and cardiac filling pressure was decreased by pooling blood in the lower extremities (lower body negative pressure (LBNP]. LBNP at -20 mmHg had no significant effects on systemic arterial pressure or heart rate but increased plasma norepinephrine concentration by 48 +/- 6% (p less than 0.001). Both the acid and the alkaline responses to SF were significantly attenuated during LBNP (-38 +/- 8%, p less than 0.01, and -55 +/- 14%, p less than 0.05, respectively). Analysis of the relationship between acid and HCO3 secretion in individual experiments suggested a relatively more pronounced inhibition of HCO3 secretion. The results imply that a decreased responsiveness of the gastric mucosa may be one component of the cardiovascular reflex adaptation to hypovolemia. A downregulation of active secretion will lead to smaller metabolic demands from the secreting cells and may thereby help to maintain a vasoconstriction in the gastric mucosa. PMID- 2305208 TI - The benefit of colonoscopy. AB - In a prospective study involving 833 consecutive outpatient and open-access colonoscopies, attempts were made to characterize the benefit of colonoscopy in terms of both predicted and unpredicted findings and therapeutic procedures. The endoscopist therefore predicted the endoscopic findings before the endoscopy. The results were compared for the different indications for colonoscopy. The overall agreement between the predictions and the colonoscopic findings was 61%. Clinically significant abnormalities were found in about half the examinations. The most frequent abnormal findings were benign polyps (24%), inflammatory bowel disease (17%), and malignancy (5%). In about half the patients with a malignancy the indication for colonoscopy was rectal bleeding, and half of the malignancies were not predicted. The greatest benefit of colonoscopy was found in patients referred because of overt rectal bleeding or occult faecal blood, and abnormal barium enema or endoscopy findings. The importance of complete colonoscopy in connection with operation for colorectal carcinoma is emphasized. PMID- 2305209 TI - Factors of prognostic importance in primary biliary cirrhosis. AB - To determine survival and the risk factors of death in primary biliary cirrhosis, data from 52 symptomatic and 13 asymptomatic patients were analyzed. The mean follow-up time was 6.3 years (range, 0.4-23 years). The average length of survival was 18 years for the symptomatic and 8.4 years for the asymptomatic patients. By a univariate analysis, ascites, presence of esophageal varices, gastrointestinal bleeding, jaundice, hepatomegaly and the logarithms of albumin and bilirubin were all associated with a poor prognosis. A multivariate analysis of the clinical features showed that the presence of bleeding from esophageal varices and the logarithm of bilirubin were the only predictors for poor prognosis. The survival of the symptomatic patients is longer than reported previously, while the life expectancy for the asymptomatic patients seems no better than for the symptomatic group. PMID- 2305210 TI - Hydrolysis of phosphatidylinositol by human pancreatic phospholipase A2. AB - Pure human pancreatic phospholipase A2 efficiently hydrolyzed the 2-ester bond of 14C-2-linoleoyl and 14C-2-arachidonyl phosphatidylinositol (PI). The rate of hydrolysis varied markedly with the bile salt (sodium taurocholate to sodium taurodeoxycholate, 3:4 mol/mol) concentration, the hydrolysis being decreased with increasing bile salt to PI ratio. The influence of bile salts was thus similar to that which has earlier been described for the hydrolysis of phosphatidylcholine (PC) with pig pancreatic phospholipase A2. When 2-3H arachidonyl PC and 2-14C-arachidonyl PI were incorporated into a mixed substrate, PI was hydrolyzed even faster than PC, the hydrolysis of both phospholipids varying in the same manner with bile salt concentration. 2-14C-arachidonyl PI was also efficiently hydrolyzed by human duodenal content, although at a somewhat slower rate than 2-3H-arachidonyl PC. It is concluded that PI is a good substrate for human phospholipase A2. This minor but arachidonate-rich dietary phospholipid may thus be digested and absorbed by pathways similar to those of the major dietary and bile phospholipid, phosphatidylcholine. PMID- 2305211 TI - DNA ploidy, tumour site, and prognosis in colorectal cancer. A flow cytometric study of paraffin-embedded tissue. AB - DNA ploidy patterns were studied by flow cytometry in nuclear suspensions from 149 paraffin-embedded colorectal adenocarcinomas. The DNA ploidy of rectal tumours was not significantly different from that of colonic tumours. Patients with DNA diploid tumours had a significant survival advantage compared with patients with non-diploid tumours, but DNA ploidy did not confer any significant additional prognostic information when tumour site, Dukes's stage, the invasiveness of the tumour, and the number of lymph node metastases were adjusted for in a proportional hazards regression analysis (Cox). It is concluded that DNA ploidy does not contribute significantly to the explanation of why patients with rectal cancer have a poorer prognosis than those with colonic cancer. PMID- 2305212 TI - Alterations in C1 inhibitor and clotting factor concentrations in primary biliary cirrhosis and other chronic liver diseases. AB - C1 inhibitor and von Willebrand factor (vWF) levels were studied in patients with cholestatic or hepatocellular liver diseases. The vWF levels were greatly increased in hepatocellular liver diseases, whereas C1 inhibitor levels were slightly reduced. In cholestatic disease both the vWF and the C1 inhibitor levels were increased: among patients with primary biliary cirrhosis these increases were more pronounced in symptomatic patients than in asymptomatic ones. When compared with other protease inhibitors, the C1 inhibitor pattern in liver disease most closely resembled that of alpha 1-antitrypsin. Thus, C1 inhibitor levels cannot be used as a measure of residual hepatocyte mass in PBC; our data, however, suggested that antithrombin may be more suitable for that purpose. PMID- 2305213 TI - Thickness of Brunner's glands and its clinical significance in duodenal ulcer disease. AB - The thickness of Brunner's glands was measured with an ocular micrometer in 75 cases of surgically resected duodenal ulcer and in 75 autopsy cases (control group). Endoscopic findings before operation were also studied. Maximum mean thickness of Brunner's glands in the control group was 1.54 +/- 0.38 mm (mean +/- SD), and no regional difference in thickness was noted. The thickness of Brunner's glands in the duodenal ulcer group was widely distributed, from 0.5 mm to 5.0 mm, and the average value was 3.0 +/- 1.0 mm, with a statistically significant difference from that of the control group. In most duodenal ulcer cases Brunner's glands were thickest within 1 cm from the center of an ulcer. Only six cases of duodenal ulcer (8.0%) showed a diffusely thin layer of Brunner's glands, less than 1.5 mm thick. These results show that the Brunner's glands become hyperplastic in duodenal ulcer patients, especially near the ulcer. In the healed ulcer Brunner's glands were thin at the center of an ulcer scar, and the average thickness was 0.42 +/- 0.26 mm. This histologic finding corresponded to the depressed scarred area observed endoscopically, suggesting a decreased mucosal resistance at this area. PMID- 2305214 TI - Morphologic changes in the small intestine after chronic alcohol consumption. AB - The morphology of the small-intestinal mucosa was studied in 11 alcoholic patients admitted to hospital for detoxification. A first biopsy specimen from the small intestine was taken as soon as possible after admission and a second specimen after about 6 weeks of abstinence. The specimens were studied in the light microscope, in the scanning electron microscope, and by immunohistochemistry. Morphometrically, a slight reduction in villus height in relation to crypt depth was observed. One patient had a subtotal villus atrophy. After abstinence the villus height was increased in five of the six patients who accepted a second biopsy. No obvious changes were seen in the frequency and appearance of peptidergic nerves or endocrine cells. Ultrastructurally, pronounced alterations were seen in the surface ultrastructure of the enterocytes. In two specimens bacterial adhesion to the mucosal surface was also found. The ultrastructural changes were unaltered after abstinence. In serum the concentrations of zinc were reduced, and the levels of copper were elevated compared with a group of teetotallers. A recently developed marker of high alcohol consumption, carbohydrate-deficient transferrin, was as good an indicator as the other conventional biochemical markers. PMID- 2305215 TI - Effect of gastrectomy with either Roux-en-Y or Billroth II anastomosis on small intestinal function. AB - This prospective study was undertaken in patients scheduled for gastrectomy for peptic ulcer disease to determine the effect of partial gastrectomy with either Roux-en-Y (n = 11) or Billroth II anastomosis (n = 11) on the function of the small intestine. Patients were studied before and at 6 months (blood and small intestinal function tests) and at 24 months (blood tests) postoperatively. Median postoperative body weights at 6 months (70.5 kg; p less than 0.01) and 12 months (70.3 kg; NS) were lower than preoperatively (73.0 kg). Haemoglobin concentrations at 6 months (8.9 mM; p less than 0.01) and at 24 months (9.1 mM; p less than 0.05) were also significantly reduced compared with the preoperative value (9.5 mM). However, neither at 6 nor at 24 months postoperatively were there significant changes for serum iron, iron saturation, folic acid, vitamin B12, protein, albumin, alkaline phosphatase, and calcium concentrations. Whereas no significant deterioration of the absorption of D-xylose and vitamin B12 or of faecal fat excretion was observed, the orocoecal transit time was significantly shortened from 98 to 50 min (p less than 0.01), the expiratory hydrogen excretion after a 50-g oral glucose load was significantly increased from 8 to 54 ppm (p less than 0.01), as was indicanuria from 257 to 368 mumol/24 h (p less than 0.01). Apart from a lower serum iron concentration and iron saturation index in the Roux-en-Y patients 6 months postoperatively (p less than 0.05), no significant differences between the two types of anastomosis were observed. It is therefore concluded that both in patients with Roux-en-Y and in those with Billroth II anastomosis most abnormalities observed after gastrectomy are secondary to an accelerated small-intestinal transit. PMID- 2305216 TI - Modern trends in osteoarthritis research. Proceedings of a satellite symposium to the Vth EULAR Symposium. Paris, France, 10-12 November 1988. PMID- 2305218 TI - The relevance of animal models in osteoarthritis. AB - Studies of osteoarthritis (OA) in humans are restricted by the slow rate at which the disease progresses, and the limited opportunity for study of the tissue changes over time. A range of animal models of OA have been developed which demonstrate histopathological and gross features typical of OA in humans. Animal models can be used to study OA, and to investigate the effects of a variety of agents, including so-called chondroprotective agents, on the progression of the disease. PMID- 2305217 TI - In vitro assays of chondrocyte functions: the influence of drugs and hormones. AB - Human articular chondrocytes may be cultured in three dimensions, according to a method already validated. This model allows us to study the repair processes of the cartilage, by measuring the proliferative activity of chondrocytes and the synthesis of two major constituents of matrix: proteoglycans and type II collagen. Some substances are characterised by stimulatory effect on DNA synthesis and no effect or a defective effect on matrix components: this is the case for Epidermal Growth Factor. Others are able to stimulate (hGH) or to depress (acetyl salicylic acid) both chondrocyte proliferation and matrix components synthesis. Finally, some substances called "chondroprotective", such as the glycosaminoglycan-peptide complex, GP-C (Rumalon) stimulate either the proliferative response or the synthesis of proteoglycans and type II collagen, according to the dose. PMID- 2305219 TI - Modern trends in osteoarthritis research. Introduction. PMID- 2305220 TI - Biochemical aspects of osteoarthritis. AB - The development of new technologies in the fields of cellular and molecular biology is contributing significantly to the understanding of the disease processes involved in the development and progression of human osteoarthritis (OA). In particular, the relationships between enzyme degradative pathways are becoming increasingly clear. Two prominent metalloenzymes and the specific tissue inhibitor of metalloproteinase have been studied in humans and animal models. Results indicate that such enzyme pathways may play a significant role in the degenerative tissue changes observed in OA. PMID- 2305221 TI - [Evaluation of tolerance, efficacy and safety of 3-year simvastatin use in the treatment of primary hypercholesterolemia]. AB - Simvastatin (synvinolin MK-733) is a potent inhibitor of 3-HMG-CoA-reductase, the key enzyme for cholesterol biosynthesis. To investigate the efficiency and safety of this new drug on a long term basis, simvastatin was administered for 3 years to ten patients with type II hyperlipoproteinemia. Daily dosages were 20 or 40 mg. The drug therapy produced a significant reduction in serum levels of total cholesterol (19-34%), LDL-cholesterol (26-44%) and Apo B (19-33%). Triglycerides decreased moderately (2-23%) while HDL-cholesterol and Apo A1 changed only slightly (-3 to 6% and 5-13% respectively). Simvastatin was well tolerated. No consistent adverse clinical or biochemical effects were observed during the three year therapy. The results indicate that simvastatin is a promising new therapy for high risk hypocholesterolemic patients. PMID- 2305222 TI - [Physical examination in screening for breast cancer: who benefits?]. AB - A survey was undertaken among a representative sample of the female population, aged 20 to 74, of the Canton of Vaud, Switzerland (total population 550,000) to assess the knowledge, attitudes and practices of women in respect to breast cancer and its prevention. The present study focuses on access by women to medical preventive measures (breast examination by physician and information on breast self-examination). The data are analyzed in relation to the individual risk factors affecting women, in particular age. While with age the risk of breast cancer grows in a linear fashion, the proportion of women having their breast examined by a physician declines. Women over 50 who had no children before the age of 30 constitute an especially high risk category, with the lowest access to information and prevention. This is explained in large part by the fact that they consult gynecologists less often. In this regard it should be noted that a visit to a gynecologist's office is associated much more often with breast examination than a visit to a family physician. It is important to take such findings into account in providing more appropriate and complete care for those groups. This involves sensitization of the physician and improved information for the women themselves. PMID- 2305223 TI - [Evaluation of Pen meters for blood glucose analysis in ambulatory diabetics]. AB - A recently developed pen-sized glucose meter using direct electrochemistry to give an automatic digital readout of the blood glucose concentration was evaluated in 10 diabetic outpatients using it at home for 8 weeks. The pen-meter readings were compared with whole blood glucose results obtained in the laboratory on an ACP-glucose analyzer. Regression statistics with slope and intercept, respectively, were 0.96% and 0.39 mmol/l (correlation coefficient r = 0.95). During the first two weeks, 53% of the patient-performed pen-meter readings differed by more than 10% from the laboratory values, during week 7 and 8 only 34%. Patients' replies to a questionnaire revealed that all welcomed the pen-meter as a fast, easy to use and highly portable device for self monitoring of blood glucose. PMID- 2305224 TI - [The value of epidural analgesia in acute pancreatitis]. AB - We report on a patient with acute pancreatitis whose pain was resistant to simultaneous administration of morphine, procaine and Buscopan. This episode was complicated by development of hypertension, tachycardia, angina pectoris, ventricular arrhythmias and electrocardiographic modifications. Analgesia was provided by epidural administration of fentanyl and bupivacaine and brought about rapid resolution of all symptoms. The usefulness of epidural analgesia in acute pancreatitis is discussed. PMID- 2305225 TI - [Clinical aspects of severe digitalis poisoning and its treatment with and without digoxin-specific antibodies. 3 case reports]. AB - Although elevated digitalis concentrations are often observed, symptomatic intoxications occur less frequently. We report the course in three patients with extremely elevated digitalis concentrations as examples of the poor correlation between measured serum levels and symptoms. In view of the cost of treatment by fab-fragments and the lack of a close dose-related effect of digitalis, we suggest restricting the use of fab-fragment therapy to patients with severe hyperkalemia or hemodynamically relevant arrhythmias. PMID- 2305226 TI - [Secondary transport of intensive care patients in Switzerland. Results of a survey]. AB - This study addresses the frequency and circumstances of secondary transportation of intensive care patients in Switzerland by evaluation of a questionnaire sent to all recognized intensive care units. Surprisingly many critically ill (roughly speaking two full ICUs with 8 patients) are transferred daily between Swiss hospitals, which amounts to about 6000 transfers per year. Pediatric cases make up 1/4 of the transfers and follow a rather common pattern, since pediatric units prefer to pick up their patients in the primary hospital with their own personnel and also to transfer them later in the same way. For adult patients no common pattern is recognizable except as regards admissions, which are usually performed by the primary hospital's facilities. We suspect a considerable degree of improvisation around secondary transfers of adults. Well trained personnel, suitable ambulances, good communication and a reasonable degree of monitoring are desirable. Non invasive monitoring techniques are considered mandatory or at least helpful by most of the answering units, whereas invasive monitoring was generally judged superfluous. The large number of secondary patient transfers and their only moderately standardized organization patterns make further research desirable. PMID- 2305227 TI - [Intrahospital transportation in large hospitals]. AB - In July 1989 an enquiry was conducted among all intensive care units with more than 6 beds regarding their experience of intrahospital transport of critically ill patients. The results are presented and commented on. The study then deals with some of the specific problems which arise when critically ill patients have to be moved within the hospital. Recent publications and our own experience concerning transport of ventilator-dependent patients suggest that there should at least be monitoring of expiratory volumes. Ventilation of the patient by portable mechanical ventilator has proven superior to manual ventilation since mechanical ventilation is more consistent and therefore fewer hemodynamic complications are to be expected. A simple device is described involving suction (by means of an injector run on oxygen) and an oxygen delivery system including an outlet into which the respirator can be plugged direct. A small shelf which can be easily attached to the bed has proven helpful during transport. PMID- 2305228 TI - [Monitoring during secondary transportation]. AB - Stabilization of the vital functions of critical patients prior to transport is mandatory even in urgent interhospital transfers. Although distances may be short, hasty transport is potentially harmful for the patient. The monitoring systems available for emergency care today facilitate mobile intensive care medicine. However, there are still technical limitations which may compromise the continuous invasive monitoring already installed before transport. Special care is needed in developing combinations of monitoring and treatment systems, especially for the transport of critically ill and injured patients. PMID- 2305229 TI - [The collecting principle in pediatrics and neonatology]. AB - Quality medical care during transport of critically ill pediatric and neonatal patients is only possible if the referring hospital and the regional center cooperate closely. The experience of physicians and nurses involved is of great importance, and the choice of the transporting team should depend on the medical status of the patient and the skills of the physicians and nurses or paramedics. Critically ill children and neonates should be transported by specialized teams. Our statistics from the last 12 years show an increasing number of transports, with the majority of patients being referred from peripheral hospitals. PMID- 2305230 TI - [Transportation of patients in the prehospital phase: education of physicians]. AB - Pre-hospital emergency medicine is developing in Switzerland. At present, however, there is no training standard for this specific and sometimes confusing aspect of extra-hospital activity. Some of the training courses which exist in other countries are recalled and the number of emergency medical transportations in Switzerland is estimated. The training programs of fourteen Swiss hospitals which cooperate with ambulance or helicopter rescue services are then presented. An enquiry by the Centre Hospitalier Universitaire Vaudois (CHUV) among 46 physicians participating regularly in Swiss Air Rescue (REGA) helicopter operations shows the very varied pathology involved and the problems encountered in creating a training program of this kind. PMID- 2305231 TI - [Short-term dobutamine therapy in severe cardiac insufficiency]. AB - The feasibility of heart transplantation has stimulated new interest in the therapy of severe refractory congestive heart failure even as an interim solution. We studied the hemodynamics, clinical efficacy and practical implications of a 72-hour dobutamine infusion in 11 patients with NYHA IV refractory congestive heart failure (age 40-73, average 55 years). The dose was 250-1000 micrograms/min, with the goal of increasing cardiac output by 30-50%. Changes in the pharmacokinetics of lidocaine were studied by single dose kinetics in 7 patients. Cardiac output increased from 2.94 +/- 0.68 to 4.77 +/- 1.1 l/min and stroke volume from 35 +/- 10 to 56 +/- 12 ml (p less than 0.001). Pulmonary capillary wedge pressure decreased from 28.5 +/- 5 to 21 +/- 6 and central venous pressure from 14 +/- 6 to 7 +/- 3 mm Hg (p less than 0.007). There was marked worsening of hemodynamics 24-48 h after starting dobutamine. However, after withdrawal of dobutamine a significantly higher cardiac output and stroke volume (3.73 +/- 0.43 l/min, 42 +/- 7 mm Hg. p less than 0.05) persisted. Both clearance and distribution volume of lidocaine increased, while half life decreased significantly (6.61 +/- 1.43 to 5.33 +/- 0.77 h. p less than 0.05). 9 of 11 patients developed Lown IVb ventricular arrhythmia, while in 4 massive diuresis occurred necessitating volume substitution. 6 patients left hospital clinically improved, 2 were transplanted and 3 patients died 1 day to 3 weeks after ending dobutamine. Dobutamine had salutary hemodynamic and clinical effects outlasting the duration of dobutamine therapy. Due to its arrhythmogenic effects it should be administered under ECG monitoring. In patients treated with lidocaine, upward dose adjustments may be necessary with improving hemodynamics. PMID- 2305233 TI - Grass roots. PMID- 2305234 TI - To D.N.R. is against the law? PMID- 2305232 TI - [Preliminary experiences with the treatment of shock in horses with a plasma expander from a starch base]. AB - HAES Steril 10% is a colloidal plasma expander rarely used in veterinary medicine. In this study HAES was used in clinical cases for the treatment of shock and in a comparative hypervolemic hemodilution study (HAES versus lactated Ringer's solution) using two experimental horses. Injection of a HAES volume equivalent to 10% of estimated blood volume resulted in a highly significant drop in PCV and in a significant drop in total protein concentration. Half live of HAES was approximately two hours. No incompatibility reactions were observed. In man HAES improves microcirculation. Studies in progress may confirm a similar effect in the equine. PMID- 2305235 TI - Battered wife syndrome: overview and presentation in the office setting. AB - Spouse abuse is an under diagnosed entity in primary care. It is common in all social classes of both men and women. It is a cyclic phenomenon that tends to increase in severity and frequency. This article reviews the psychological factors of the man and the woman; the signs and symptoms of abuse; the reasons abused women stay or leave, and treatment modalities. Also discussed are the results of two studies performed by the authors. The first study was an anonymous survey of 218 women to determine the rate of spouse abuse to female patients in two family practice clinics. In the second study 14 clinic patients who volunteered for an interview were asked what they expected from their family doctor in regards to spouse abuse. PMID- 2305236 TI - The state of South Dakota's child: 1989. AB - The 1987 infant mortality in South Dakota returned to a rate below that of the nation as had been the trend for the eight years prior to 1986. Comparisons of South Dakota and the United States data show that for both whites and non whites the mean five year neonatal mortality rates were below those of the nation. Alternately, the South Dakota white post neonatal mortality rate is slightly higher than that of the nation and the non white post neonatal mortality rate is more than three times higher than that of the United States. Comparisons of the causes of post neonatal deaths show that the relative risk of death from potentially preventable causes is four times higher among South Dakota non whites as whites. The paper concludes with a discussion of the incidence of child abuse and neglect and the important role health care providers may play in preventing and treating this cause of significant mortality and morbidity of children. PMID- 2305237 TI - Hand tumors: extraskeletal chondroma and osteoma--case reports. AB - Superficially simulating ganglion, extra skeletal tumors of cartilage and bone may occur in the soft tissues of the hand with no relation to the skeleton. Typical examples are presented with the pathological findings and clinical findings. PMID- 2305238 TI - Effect of dry deposition, washout and resuspension on radionuclide ratios after the Chernobyl accident. AB - The temporal variations of radionuclide ratios in air and deposition samples collected simultaneously at Munich-Neuherberg (F.R.G.) after the Chernobyl accident have been studied. Until 8 May 1986, the radionuclides investigated were 99Mo, 103Ru, 106Ru, 110mAg, 125Sb, 129mTe, 132Te, 131I, 134Cs, 137Cs, 140Ba, 141Ce and 144Ce. After 8 May, 99Mo, 110mAg, 125Sb, and the Ce isotopes were below the detection limits. Considerable temporal variations of the above radionuclides, relative to 137Cs, were observed in air as well as in deposition. In air the temporal variations reflect the arrival of different parts of the reactor plume with different elemental composition. In deposition, the temporal patterns were quite different from those in air for a given radionuclide. This is explained by varying contributions of dry and wet deposition. Until 8 May, the washout ratios of the above radionuclides covered a range from 240 to 5600, with smaller variations for all radionuclides within one event (e.g. 460-910), and larger variations from one event to another (e.g. 460-3300 for 137Cs). The dry deposition velocity of 137Cs was found to be 0.27 cm s-1, similar to that of 110mAg, aerosol 131I and 140Ba (0.37, 0.13 and 0.15 cm s-1). Another group of radionuclides includes 103Ru, 106Ru, 125Sb, total 131I and 132Te with dry deposition velocities of 0.08, 0.10, 0.07, 0.03 and 0.08 cm s-1 and with temporal variations in deposition which are quite different from those of the first group. From 8 May to the end of June, the washout ratios increased to values between 1500 and 24,000, with the exception of iodine, which had considerably lower washout ratios of between 37 and 4400. These later effects are explained by resuspension and, in the case of iodine, by remobilization of gaseous species. PMID- 2305240 TI - Feeding ecology of the stone and pine marten revealed by element analysis of their skeletons. AB - Feeding habits of free-ranging martens (Martes martes and Martes foina) are evaluated by means of trace element and stable carbon isotope analyses of their skeletons. This investigation was carried out as an inter-disciplinary project of both wildlife biology and physical anthropology. As a result, data are obtained on the feeding ecology of the two species; in addition, a baseline is provided for dietary reconstruction of past human populations. Both species of martens are omnivorous feeders, M. martes being slightly more carnivorous than M. foina. Diversity of dietary intake with respect to plant food and animal protein is only one-third of the maximum divergence between strict herbivores and carnivores. PMID- 2305239 TI - Lead intake and blood lead in two-year-old U.K. urban children. AB - A comprehensive study of a group of 2-year-old urban children (n = 97), designed to provide quantitative information simultaneously for lead intakes via all identified pathways, has been carried out in Birmingham (U.K.). Results showed that for children whose blood levels and exposure to environmental lead were within the normal range for the U.K., blood lead concentration was significantly related to a combination of house dust lead loading and an overall rate of touching objects, to water lead concentration and to the parents' smoking habits. On the basis of assumptions used by the Royal Commission on Environmental Pollution (RCEP), the estimated average total uptake of lead was 36 micrograms day-1; of this, 97% was from ingestion from dust, food and water and only 3% from inhalation. PMID- 2305241 TI - Uranium concentration in bone of Beijing (China) residents. AB - Bone samples were obtained from 65 Beijing residents who had died from illness or old age. The concentration of uranium in the bone ash was determined by the laser fluorimetric method. The concentration varied between 0.014 and 0.390 microgram g 1 ash, with a median value of 0.067 microgram g-1 ash; the 25th and 75th percentiles were 0.045 and 0.1 microgram g-1 ash respectively. The arithmetic mean was 0.083 microgram g-1 ash. The concentration of uranium in bone (ash) correlated with age, but not with sex; uranium participates in the bone calcification process. PMID- 2305242 TI - Transfer of environmental plutonium and americium across the human gut: a second study. AB - A follow-up to our previous study is described on human gut transfer factors for plutonium and americium in winkles harvested from the shoreline near the British Nuclear Fuels plc Sellafield reprocessing plant. Six male and two female adult volunteers ate single quantities of shellfish; samples of their urine before and after consumption were analysed. As in the previous study, the plutonium and americium excreted were difficult to detect, and counting times of approximately 8 weeks were employed. Results are presented in detail to allow further interpretation, but preliminary assessment has been carried out on the basis of published data for excretion following transfer to blood. The mean and range obtained for the gut transfer for plutonium was 1.3 (0.2-3.2) x 10(-4); for americium the result was 0.8 (0.4-1.7) x 10(-4). Combined with the results of the previous study when interpreted on the same basis, the results were 1.7 (0.2-4.9) x 10(-4) and 0.9 (0.3-2.8) x 10(-4), respectively. No significant evidence was revealed in this study for differences in gut transfer between males and females, nor for seasonal differences, e.g. due to differences in form of incorporation of actinides in shellfish. For realistic assessments of doses due to shellfish consumption near Sellafield, to assess compliance with criteria recommended by the International Commission on Radiological Protection (ICRP), a suitable value for the gut transfer factor of both plutonium and americium might be 2 x 10(-4). A value of 5 x 10(-4) would appear to be cautious. PMID- 2305243 TI - Contamination of eggs, poultry liver and bovine liver and kidney by chlorinated pesticides in Morocco. AB - Study of the contamination of eggs, poultry liver, and bovine liver and kidney by chlorinated pesticides, using gas liquid chromatography, demonstrated that lindane and hexachlorobenzene were the two most prominent contaminants: they were found respectively in 86 and 93% of samples, 7.5% of which contained levels higher than international tolerance levels. PMID- 2305244 TI - Blood lead levels of Beijing (China) citizens. AB - Lead levels were determined in 856 blood samples obtained from Beijing citizens who were either factory workers or clerks with no known occupational exposure to heavy metals including lead. Additional analyses were conducted on 74 samples from factory workers in the small city of Jinxi, China. The geometric mean blood lead level (Pb-B) among the general Beijing population 99.2 and 76.1 micrograms 1 1 for non-drinking and non-smoking men and women, respectively, with a statistically significant difference between the two sexes. The effect of drinking was not detectable, whereas that of smoking was suggested, but not conclusive. The Pb-B levels among Jinxi workers did not differ from the levels among Beijing citizens. The Pb-B for inhabitants of Beijing was similar to the levels of inhabitants of a medium-sized city, Hefei, and lower than the values for residents of two heavily industrialized large cities, Shanghai and Shenyang. The values for Chinese citizens appear to be higher than those for Japanese and Korean farmers, but the possibility of urban-rural differences remains to be examined. PMID- 2305245 TI - Cadmium exposure and health effects among residents in an irrigation area with ore dressing wastewater. AB - About 0.05 mg Cd l-1 was found in the irrigation water contaminated by the wastewater discharged from tungsten ore dressing plants, and about 1 mg Cd kg-1 was found in irrigated acid soils. The main sources of cadmium intake by residents of the polluted areas are agricultural products. The average intake of cadmium was 367-382 micrograms day-1, and for smokers 417 micrograms day-1. Among the residents who have been exposed to cadmium for more than 25 years, cadmium absorption (urinary cadmium greater than or equal to 10 micrograms g-1 creatine) was 60% and an early effect on the target organ (urinary cadmium greater than or equal to 15 micrograms g-1 creatinine and urinary beta 2-microglobulin greater than 500 micrograms g-1 creatinine) was detected in 17% of the sample of 433 persons. Levels of urinary cadmium and blood cadmium exceeded the critical value in the exposed group. The concentrations of urinary calcium, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase were significantly higher in residents of contaminated areas than in those of control areas. Case-control study of the residents shows that many have suffered from a nephropathy with tubulo interstitial abnormalities. Owing to the combined cadmium effect, the cases with fractional beta 2-microglobulin excretion greater than 0.10 were 46% in the exposed population, and were much higher than that in the control group (20.3%). PMID- 2305247 TI - Priority one: rescue the environment. PMID- 2305246 TI - Heavy metal contents of paddy fields of Alcacer do Sal, Portugal. AB - Recent claims of metal contamination in the lower reaches of the Sado River, in the Alcacer do Sal region, Portugal, a major rice-producing area were investigated by carrying out metal surveys in the area. The elements Fe, Mn, Zn, Cu and Pb were measured in the soil and in rice plant parts--roots, shoots and grain--as well as in some weeds growing in the Sado banks, near the paddy fields. Results showed that the metal contents of paddy soils were similar to background concentrations, with the exception of Zn and Cu, which were above those concentrations and reached their highest levels at Vale de Guizo, the monitored station located furthest upstream in the Sado River. At some sites, plant roots accumulated relatively large amounts of Fe, Mn, Zn and Cu, but the shoot levels of these metals were within the normal range for rice plants. It is possible that varying, but significant, amounts of Fe associated with the roots were in the form of ferric hydroxide plaque covering their surfaces. Copper levels in the shoots of rice were below the normal contents cited for this plant in the literature. Metal levels of river sediments collected near Vale de Guizo seem to corroborate the possibility of some metal contamination in the Sado River, most probably derived from pyrites mining activity in the upper zone of the Sado basin. PMID- 2305248 TI - New World epidemics. PMID- 2305251 TI - Old law puts a new wrinkle in fraud probes. PMID- 2305250 TI - Hearing on lab vandalism. PMID- 2305249 TI - Evolutionary questions: the "progenote". PMID- 2305252 TI - Science indicators: healthy--for now. PMID- 2305253 TI - Concerns raised about mouse models for AIDS. PMID- 2305254 TI - Race and imprisonment decisions in California. AB - Data were analyzed for 11,553 California offenders who in 1980 were convicted of assault, robbery, burglary, theft, forgery, or drug crimes. Whether an offender was given probation or sentenced to prison for such crimes could be predicted with about 80 percent accuracy from a combination of variables that described defendant and crime characteristics and criminal justice processing. The addition of race to the prediction equation for a given crime type did not improve the accuracy of the prediction. In addition, there was no evidence that other factors related to imprisonment (for example, number of conviction counts, going to trial) masked a relation between race and imprisonment. Race also was not related to the length of prison term imposed. PMID- 2305255 TI - Endocranial features of Australopithecus africanus revealed by 2- and 3-D computed tomography. AB - The earliest hominid from South Africa, Australopithecus africanus, is known from only six specimens in which accurate assessment of endocranial capacity and cranial venous outflow pattern can be obtained. This places a severe limit on a number of hypotheses concerning early hominid evolution, particularly those involving brain-body size relationships and adaptations of the circulatory system to evolving upright posture. Advances in high-resolution two- and three dimensional computed tomography (CT) now allow the inclusion of another important specimen to this list, MLD 37/38 from Makapansgat. A new computer imaging technique is described that "reconstructs" the missing portions of the endocranial cavity in order to determine endocranial capacity. In addition, CT evaluation allows assessment of cranial venous outflow pattern even in cases where the endocranial cavity is completely filled with stone matrix. Results show that endocranial capacity in this specimen is less than originally proposed and also support the view that gracile and robust australopithecines evolved different cranial venous outflow patterns in response to upright postures. PMID- 2305256 TI - Expanded HIV-1 cellular tropism by phenotypic mixing with murine endogenous retroviruses. AB - In view of the current interest in in vivo murine models for acquired immunodeficiency syndrome (AIDS), the interaction between human immunodeficiency virus type 1 (HIV-1) and endogenous murine leukemia virus (MuLV)-related retroviruses was investigated with a human leukemic T cell line (PF-382x) that acquired xenotropic MuLV (X-MuLV) after in vivo passage in immunosuppressed mice. Despite similar levels of membrane CD4 expression and HIV-1 125I-labeled gp 120 binding, a dramatic acceleration in the time course of HIV-1 infection was observed in PF-382x compared to its X-MuLV-negative counterpart (PF-382). Moreover, PF-382 cells coinfected by X-MuLV and HIV-1 generated a progeny of phenotypically mixed viral particles, enabling HIV-1 to productively infect a panel of CD4- human cells, including B lymphoid cells and purified normal peripheral blood CD4-/CD8+ T lymphocytes. Mixed viral phenotypes were also produced by human CD4+ T cells coinfected with an amphotropic MuLV-related retrovirus (A-MuLV) and HIV-1. These data show that endogenous MuLV acquired by human cells transplanted into mice can significantly interact with HIV-1, thereby inducing important alterations of HIV-1 biological properties. PMID- 2305257 TI - Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K+ channels. AB - Sulfonylurea-sensitive adenosine triphosphate (ATP)-regulated potassium (KATP) channels are present in brain cells and play a role in neurosecretion at nerve terminals. KATP channels in substantia nigra, a brain region that shows high sulfonylurea binding, are inactivated by high glucose concentrations and by antidiabetic sulfonylureas and are activated by ATP depletion and anoxia. KATP channel inhibition leads to activation of gamma-aminobutyric acid (GABA) release, whereas KATP channel activation leads to inhibition of GABA release. These channels may be involved in the response of the brain to hyper- and hypoglycemia (in diabetes) and ischemia or anoxia. PMID- 2305258 TI - Biotechnology on the auction block. PMID- 2305259 TI - U.S. lags on birth control development. PMID- 2305260 TI - Mathematics untwists the double helix. PMID- 2305261 TI - Studies of unusual simple molecules by neutralization-reionization mass spectrometry. AB - Reactive or unstable molecules are key intermediates in many important reactions, but can be difficult to prepare for experimental studies. Species with missing (:CH-OH) or extra (H3) substituents can often be formed conveniently in the gas phase by neutralizing a beam of a more stable ionic counterpart (CH = O+H, H3+). Reionization of the neutral after approximately 10(-6) seconds tests its stability, whereas its unimolecular chemistry can be probed by preparing it with different amounts of internal energy. The resulting neutral products are reionized and mass analyzed. Isomers are then characterized by ion dissociation and a third mass-analysis step. Many unusual molecules have been characterized with this technique, which can also be used to probe complex unimolecular chemistry, such as that of cyclobutadiene and ethylene oxide. PMID- 2305262 TI - The MerR metalloregulatory protein binds mercuric ion as a tricoordinate, metal bridged dimer. AB - Bacterial MerR proteins are dimeric DNA-binding proteins that mediate the Hg(II) dependent induction of mercury resistance operons. Site-directed mutagenesis of the Bacillus sp. RC607 MerR protein reveals that three of four Cys residues per monomer are required for Hg(II) binding at the single high-affinity binding site. Inactive mutant homodimers can exchange subunits to form heterodimers active for Hg(II) binding. Studies of a heterodimer retaining only three of eight cysteine residues per dimer reveal that Cys79 in one subunit and Cys114 and Cys123 in the second subunit are necessary and sufficient for high-affinity Hg(II) binding in an asymmetric, subunit bridging coordination complex. PMID- 2305263 TI - Ligand-induced transformation by a noninternalizing epidermal growth factor receptor. AB - Identification of a mutant epidermal growth factor (EGF) receptor that does not undergo downregulation has provided a genetic probe to investigate the role of internalization in ligand-induced mitogenesis. Contact-inhibited cells expressing this internalization-defective receptor exhibited a normal mitogenic response at significantly lower ligand concentrations than did cells expressing wild-type receptors. A transformed phenotype and anchorage-independent growth were observed at ligand concentrations that failed to elicit these responses in cells expressing wild-type receptors. These findings imply that activation of the protein tyrosine kinase activity at the cell membrane is sufficient for the growth-enhancing effects of EGF. Thus, downregulation can serve as an attenuation mechanism, without which transformation ensues. PMID- 2305264 TI - Mini-mouse: disruption of the pygmy locus in a transgenic insertional mutant. AB - A founder transgenic mouse harbored two different integration patterns of a transgene at the same locus, each of which gave rise to a similar autosomal recessive mutation. Mice of the mutant phenotype were of small stature but had normal levels of growth hormone. The disrupted locus was cloned, and a genetic and molecular analysis showed that the insertional mutants were allelic to a spontaneous mutant, pygmy. The mice should be a useful model for the growth hormone-resistant human dwarf syndromes and could lead to a greater understanding of the pathways involved in growth and development. PMID- 2305265 TI - A family of three mouse potassium channel genes with intronless coding regions. AB - To understand the molecular mechanisms responsible for generating physiologically diverse potassium channels in mammalian cells, mouse genomic clones have been isolated with a potassium channel complementary DNA, MBK1, that is homologous to the Drosophila potassium channel gene, Shaker. A family of three closely related potassium channel genes (MK1, MK2, and MK3) that are encoded at distinct genomic loci has been isolated. Sequence analysis reveals that the coding region of each of these three genes exists as a single uninterrupted exon in the mouse genome. This organization precludes the generation of multiple forms of the protein by alternative RNA splicing, a mechanism known to characterize the Drosophila potassium channel genes Shaker and Shab. Thus, mammals may use a different strategy for generating diverse K+ channels by encoding related genes at multiple distinct genomic loci, each of which produces only a single protein. PMID- 2305267 TI - Non-Hodgkin's lymphoma. PMID- 2305268 TI - Recent advances in cancer chemotherapy. Proceedings of a symposium of the 5th European Conference on Clinical Oncology. September 3, 1989, London. PMID- 2305266 TI - Transplanted suprachiasmatic nucleus determines circadian period. AB - The pacemaker role of the suprachiasmatic nucleus in a mammalian circadian system was tested by neural transplantation by using a mutant strain of hamster that shows a short circadian period. Small neural grafts from the suprachiasmatic region restored circadian rhythms to arrhythmic animals whose own nucleus had been ablated. The restored rhythms always exhibited the period of the donor genotype regardless of the direction of the transplant or genotype of the host. The basic period of the overt circadian rhythm therefore is determined by cells of the suprachiasmatic region. PMID- 2305269 TI - New developments in the treatment of gastric carcinoma. AB - The recent successes being achieved with combination chemotherapy regimens, such as FAMTX (fluorouracil [5-FU], doxorubicin, methotrexate), EAP (etoposide, doxorubicin, cisplatin), and ELF (etoposide, leucovorin, 5-FU), strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remissions (CRs). Moreover, some of these CRs were histopathologically confirmed. The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. Thirty-six patients with LAD had been treated in a phase II trial with preoperative EAP, inducing 24 (70%) overall remissions (two clinical CRs, six pathologic CRs, 16 partial remissions [PRs] in 35 evaluable patients. Twenty-one patients were disease-free after chemotherapy with or without second-look surgery. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease-free. The expected survival of patients with unresectable LAD is approximately 4 to 6 months without any treatment and 6 to 9 months with standard chemotherapy. Compared with the latter results, the preoperative use of effective regimens (eg, EAP) seems to improve prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stages IIIa or IIIb). However, partly because of the severe toxicities (myelosuppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens for the following reasons: Two of three patients with gastrointestinal disease are older than 60 years. Nontumorous diseases of the cardiovascular system, kidney, and others are frequent in this age group and may complicate or even prevent treatment with aggressive regimens. Considering the predominantly palliative treatment intentions in far advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination ELF in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53% (27 of 51) including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. Only 16% and 4% of patients, respectively, experienced WHO grades 3 and 4 leukopenia. Nausea/vomiting and mucositis/stomatitis were mild.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2305270 TI - Spatial patterns of use of health services in the Kingston metropolitan area, Jamaica. AB - This study focuses on the influence of distance, transport and accessibility on the use of health services in Kingston, Jamaica. It reviews various factors affecting the use of health care with particular reference to Third World cities and presents results from a case study of utilization in the Kingston Metropolitan Area. Three pairs of sites of contrasting social status were selected and 50 respondents questioned in each about spatial patterns of primary health care (PHC) attendance. Types of facility attended, mode of transport, travel times, distance and frequency of utilization were discussed. Some distinctive differences appeared between low and high status site respondents with regard to distances to facilities and travel times, which were almost always higher for the low status respondents. Most respondents were not using their nearest facilities, for varying reasons which included, for poorer respondents, need to attend frequently distant public facilities and, for wealthier respondents, loyalty to old family doctors and use of company-related doctors. The mobility of the higher status respondents afforded them considerable choice of locations used for health care and their attendance was much more convenient than that of lower status respondents. Utilization rates were somewhat higher in the high status sites although not to the extent found by some earlier studies in similar settings. PMID- 2305271 TI - Medical geography--recent case studies and concerns. Selected papers from the Third International Symposium in Medical Geography. Kingston, Canada, 7-12 August, 1988. PMID- 2305272 TI - Congenital malformations in the Fylde region of Lancashire, England 1957-1973. AB - This paper uses data collected by a consultant paediatrician to examine variations in the prevalence of neural tube and cardiovascular malformations within the Fylde region of North West England. Results at the district scale indicate contrasts in the geographical distributions of the two classes of malformation and these are then further assessed via a case-control study which standardises for factors such as date of conception, age of mother and parity. The results of this study suggest that there were wards in Blackpool and Fleetwood with unusually high prevalences of neural tube defects. Further research is being undertaken to identify the causes of these concentrations. PMID- 2305273 TI - The community perinatal health care system of urban Cape Town, South Africa--I. Characteristics of mothers and birth outcomes. AB - Greater Cape Town has developed a geographical network of perinatal health care services for low-income mothers using community-based clinics with hospital referrals. This study analyzes 25,409 births recorded in 162 different urban residential areas during 1987. The data apply to two populations--black and mixed. Information on the mother, such as height, weight, education, parity, and prenatal visits is indicated by suburb, as well as birth outcomes such as gestational age, birthweight, and method of obstetrical delivery. Comparisons are drawn between black and mixed populations and among suburbs. High utilization rates and successful maternity and infant outcomes suggest that the outreach clinics of Cape Town could provide a model for urban agglomerations in other African countries. PMID- 2305274 TI - The community perinatal health care system of urban Cape Town, South Africa--II. Geographical patterns. AB - Greater Cape Town has developed a geographical network of perinatal health care services for low-income mothers using community-based clinics with hospital referrals. This study analyzes 25,409 births recorded in 162 different urban residential areas during 1987. The data apply to two populations--black and mixed. Information on the mother, such as height, weight, education, parity, and prenatal visits is indicated by suburb, as well as birth outcomes such as gestational age, birthweight, and method of obstetrical delivery. Comparisons are drawn between black and mixed populations and among suburbs. High utilization rates and successful maternity and infant outcomes suggest that the outreach clinics of Cape Town could provide a model for urban agglomerations in other African countries. PMID- 2305275 TI - The ecology of health services utilization in Grenada, West Indies. AB - Few empirical investigations into the nature of health services utilization fully acknowledge that the home environment may act as a socio-geographic focus of both disease transmission and of learned health behavior. This paper examines the role of the home environment, as well as of personal characteristics and accessibility, in the utilization of health services in Grenada, West Indies. Bivariate and logit analyses of household survey data are employed to identify markers of high user individuals and households. Aspects of each domain of the home environment (physical and behavioral environment, demographics, and residential mobility) emerge as contributors to the utilization phenomenon in the study communities. Both etiological and socio-economic linkages are postulated to underlie the observed relationships. The implications of this work for health planning in developing countries is discussed. PMID- 2305276 TI - Housing dampness and health amongst British Bengalis in east London. AB - The paper describes a survey that was undertaken to investigate the possible associations between damp public sector housing in London (U.K.) and the health of British Bengali tenants. The problems of establishing epidemiological evidence in this field and the accurate assessment of dampness and health are addressed, and the relative importance of housing and lifestyle factors in the prevalence of damp in the home is considered. The results show that there are significant relationships between reported and measured damp, cold and mould in the home and various aspects of reported health. It is also apparent that it is aspects of housing, in particular the provision of a good heating system rather than lifestyle that determine the degree of dampness in a home. PMID- 2305278 TI - How significant are the spatial configurations of health care systems? AB - After briefly reviewing some of the problems of examining 'the spatial', this paper sets out to demonstrate the importance of examining spatial configurations of health care systems. It isolates major ordering principles for understanding such systems, namely the level of economic development, political structure and ideology, and allocational mechanism. It then assesses the role of 'the spatial' in terms of system differentiation (e.g. availability, accessibility, types of care) and as confounding or modifying the impact of the major ordering principles or ideal-typifications. It concludes by suggesting that while the role of the spatial may vary from high or low (or no) significance, it should not be ignored. The combination of spatial and societal configurations in specific or comparative analyses must be undertaken cautiously. PMID- 2305277 TI - Health based geographical information systems: their potential examined in the light of existing data sources. AB - There is much potential for the use of geographical information systems (GIS) within the management and analysis of health and health care data. This paper addresses the problems of using routine data in the creation of geographical information systems for health. The numerous sources of British official routine health information however vary greatly in their geographical coverage and geographical detail. Particular attention therefore focuses upon the extent to which existing data sets can readily be used within GIS. Recommendations for changes in the data collection process are forwarded to improve the potential for GIS use. The overall utility of geographical health information systems within health service planning is illustrated using the example of community based activities. PMID- 2305279 TI - Conceptions of space and community in British health policy. AB - Several recent United Kingdom health policy initiatives include ideas implicitly or even explicitly involving geographical space as a central theoretical construct. Neighbourhood nursing is perhaps the best known recent example. These initiatives are not without common features, and the paper commences with a typology of the roles which geographical space plays in health policy. A second section gives specific consideration to neighbourhood nursing. Thirdly the paper outlines the social theoretic debates surrounding geographic inputs to health policy: ideas such as community and locality. It is suggested that spatial conceptions in health policy reflect a complex amalgam of sociological assumptions which might fruitfully be considered in the light of Giddens' concept of locale. PMID- 2305280 TI - Activism for medical geographers: American, British and Canadian viewpoints. AB - This paper describes some of our personal efforts to launch research projects that address public health issues of interest to geographers in the United States, Canada and Britain. In pressing these agendas we have found through our experiences that there are personal and disciplinary costs associated with activism. We describe the loss of identity with geography; the frustration of trying to persuade bench scientists, corporate representatives, and government officials of the importance of our work; the loss of research time and contact with both our academic colleagues and students. PMID- 2305281 TI - Correlates of health-care use: Inuit and Cree of northern Quebec. AB - This case study of the use of health-care services in northern Quebec is the first of a series of reports dealing with the health status, risk factors and access to care of the two major aboriginal populations in this region, the Cree and the Inuit. The focus of the broader study is on the health status and risk factors in these native populations. This research, based on a survey conducted in 1983-84, describes the present health status and health-care system of the Cree and Inuit, then presents a path analysis model of their use of health services. The purpose of this approach is to provide health planners and care providers with useful information and to encourage the development of well organized and reasonable health-care service delivery to these populations. PMID- 2305282 TI - Ontario's underserviced area program revisited: an indirect analysis. AB - Financial incentive programs are used in various developed and developing countries to effect change in the geographic distribution of physicians. The Underserviced Area Program of Ontario is the longest running financial incentive program in Canada. It is described in detail and analyzed for its effectiveness in solving the problems of the maldistribution of physicians in northern Ontario. Using location quotients as an indirect measure shows that the maldistribution of physicians continues despite the implementation of the program. It is argued that the unidimensional solution of financial incentives cannot be used to solve the multidimensional issue of accessibility to health care in rural and remote areas. PMID- 2305283 TI - A framework for modeling the consumption of health services by the rural elderly. AB - This paper reports on an ongoing research program which seeks to assess the implications of population aging for housing, services and transportation in rural communities in the Province of Ontario. Specifically, the focus is on the modeling of health and social service consumption by elderly (over 65) persons. Following a review of the literature on service provision to senior citizens in Ontario, a modeling framework conceptualizing the process of service utilization at both the aggregate (user and nonuser characteristics) and individual (decision making) levels is introduced. Data on use of community support services drawn from a survey of elderly residents in two communities in Grey County, Ontario (Meaford, population 4380 in 1986, and Markdale, population 1226 in 1986) are used to illustrate the general features of the modeling framework. Particular attention is paid to the ability of the modeling framework to yield insights into the origins of notable variations in service use rates between men and women. Overall, the results are taken to be supportive of the usefulness of the modeling framework as a template for guiding empirical analysis of service utilization patterns. At the same time the case study testifies to the complex and dynamic nature of service provision issues in rural communities. The challenge of providing services effectively to an elderly rural population located in scattered villages and small towns will continue to tax the imagination and resources of responsible agencies. PMID- 2305284 TI - Socio-spatial perspectives on the utilization of emergency hospital services in two urban territories in Quebec. AB - Hospital emergency services located in urban areas have been severely congested for several years in the province of Quebec. This problem is not caused by ambulatory patients who are using emergency services as a regular source of care, but by patients in need of emergency services. To study the factors affecting the utilization rates of emergency services in two urban areas, the city of Laval and the Quebec metropolitan area, two samples of more than 30,000 patients each were drawn from the 1981 file of the Regie de l'assurance-maladie du Quebec. The utilization rates of emergency services for emergent and urgent causes in these two samples were computed on the basis of the census tract location of these patients. The socio-economic characteristics of these census tracts were taken from the 1981 Canadian census, the distance travelled from each census tract to the location of hospital emergency services was computed and included as a predictor of the utilization rates. Also, the prevalence of chronic and psychiatric diagnoses were obtained for each census tract. The result of the analysis showed that distance affected the utilization rates only in the Quebec metropolitan area where the hospitals are mostly located in the downtown area near deprived and working class neighbourhoods, while the socio-economic characteristics affected the utilization rates in both Quebec and Laval. PMID- 2305286 TI - Critical medical anthropology: theory and research. PMID- 2305285 TI - Variation in Michigan hospital use rates: do physician and hospital characteristics provide the explanation? AB - Previous small area analysis studies have shown that hospital admission rates (total, medical and surgical) vary among hospital service areas. Using 1983 Michigan hospital inpatient data from 53 nonmetropolitan Detroit lower peninsula hospital service areas, one physician characteristic and 13 hospital characteristics (in the categories of resource supply, services offered and organization) were tested for their association with and explanation of 14 hospital use rates. Registered nurses per bed and the weighted proportion of board certified physicians to total physicians were inversely related to and offered significant contribution to the explanation of the variation in total use rates and in four medical causes for admission rates (circulatory, respiratory, digestive and genito-urinary). Physician and hospital variables provided significant explanation for six of the seven surgical procedure rates tested (appendectomy, hemorrhoidectomy, cholecystectomy, inguinal hernia repair, prostatectomy and hysterectomy). Four causative factors derived from the characteristics studied were postulated to influence the hospital use rates. The first factor was the small rural nature of the average high use hospital service area. High use areas had a lower proportion of board certified physicians and fewer RNs per bed, beds per hospital, and house staff per 10,000 population than did low use areas. Another factor was the inequality in the distribution of high technology diagnostic services. High use hospital service areas had fewer diagnostic services than did low use areas. The third factor was the inequality in the rural hospital environment produced by the presence or absence of medical education programs. The fourth factor was the impact of the definition and size of a hospital service area. Current small area analysis methodology assigns every small area to a hospital service area, no matter what the probability of the population using the hospital(s) within the service area. This research questions that methodology, suggests the need for hospital service area definitions based upon the specific diagnosis or procedure being studied and postulates that some rural hospital distance decay curves may turn upward at farther distances when the immediate availability of treatment is too critical to allow patients to return to distant residences. PMID- 2305287 TI - Critical medical anthropology in question. PMID- 2305288 TI - Reinventing medical anthropology: toward a critical realignment. AB - Responding to the narrow focus, medicalization, and inattention to political economy within conventional medical anthropology, a growing number of researchers are participating in a significant restructuring of the subdiscipline. The paper examines several shortcomings of contemporary medical anthropology and, building on the work of the emergent critical trend, identifies key areas of theory and practice for furthering the critical realignment of medical anthropology. PMID- 2305289 TI - Three propositions for a critically applied medical anthropology. AB - This paper initiates a discussion of some viable approaches to a critically applied as opposed to a clinically applied medical anthropology. The old question of the role of the intellectual man or woman is at the heart of this enquiry. Analogies are drawn between the current relations of anthropology to medicine and the history of anthropology's relations to European colonialism. The dilemmas of the clinically applied anthropologists 'double agent' role is discussed and alternatives offered in the form of three separate and to some extent contradictory projects, each of which, however, demands that the anthropologists cut loose his or her moorings from conventional biomedical premises and epistemologies. Ours must be an anthropology of affliction and not simply an anthropology of medicine. Praxis must not be left in the hands of those who would only represent the best interests of biomedical hegemony. PMID- 2305290 TI - Somatizing distress: hospital treatment of psychiatric co-morbidity and the limitations of biomedicine. AB - Analysis reveals that treatment of psychiatric co-morbidity in hospitals has a somatizing effect. The patients typically have long, costly hospital stays marked by numerous nonpsychiatric consultations. When consulted, psychiatrists are constrained by their role within the hospital social system and tend to employ somatopsychic approaches which are compatible with the orientation of their physician consultees. Case studies illustrate the inadequacy of these treatment modes and highlight the significance of social and economic problems as etiologic factors in psychiatric co-morbidity. Applying a critical approach from the field of medical anthropology, we argue that the ultimate solution to many patients' problems lies outside of the realm of biomedicine and depends on changes in social policies. Thus, the limitations of biomedicine are seen as due both to its predisposition toward somatic treatment and to larger social forces which cause its practitioners to be part of the problem rather than part of the solution. PMID- 2305291 TI - Transnational tobacco companies and health in underdeveloped countries: recommendations for avoiding a smoking epidemic. AB - This paper examines the impact of transnational tobacco companies on health in underdeveloped countries and makes recommendations for avoiding a coming smoking epidemic. Although tobacco is generally seen as primarily a health problem, tobacco's future in the Third World depends upon a number of nonhealth related considerations, especially political and economic factors. Unfortunately, there is very little relationship between what the World Health Organization and others have recommended, and what most Third World countries are doing today. Although the controversy concerning cigarette smoking and health has only become a 'burning issue' in recent decades, tobacco products have been used around the world for hundreds of years. The public outcry against cigarette smoking has become increasingly widespread since the 1964 U.S. Surgeon General's report on smoking and health. The ill effects of cigarette smoking are now widely considered collectively as the number one preventable health problem in the world, responsible for an estimated 2.5 million deaths per year. In response to declining sales in developed countries, the tobacco transnational corporations have begun focusing their attention on Third World markets, where tobacco consumption has increased dramatically in recent years. Cigarettes not only take precious limited resources away from desperately needed basic human needs, but they also inflict future health problems on vast numbers of Third World people who have only a vague understanding of the risks involved in cigarette smoking. Until Third World governments address the long-term consequences of their short term lust for cash, the probabilities of a smoking epidemic in the Third World grow increasingly likely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305292 TI - Kerr-McGee and the NRC: from Indian country to Silkwood to Gore. AB - By focusing upon the Nuclear Regulatory Commission's appraisal of the Kerr-McGee Corporation's safety record in the Four Corners area and at two facilities in Oklahoma, this article examines the political economy of nuclear regulation in American society. Particular attention is given to the agency's response to intervenor groups which protested various operations at Kerr-McGee facility in Gore, Oklahoma, both prior to and following the accidental rupture of a cylinder containing uranium hexafluoride. Despite a consistent record of violations and nuclear mishaps by Kerr-McGee, the Nuclear Regulatory Commission permitted the company to essentially monitor its own activities. Rather than protecting workers and the public from the hazards of the nuclear industry, state regulation attempts to legitimize and defuse public opposition to its endeavors. PMID- 2305293 TI - Just messin' around. PMID- 2305294 TI - Histophobia. PMID- 2305296 TI - Idiopathic scoliosis: correction of lateral and rotational deformities using the Cotrel-Dubousset spinal instrumentation system. AB - The Cotrel-Dubousset instrumentation (CDI) system developed between 1982 and 1984 is now being used extensively for the posterior correction of idiopathic scoliosis. In this study we compared the lateral and rotational correction obtained with CDI to that obtained with Harrington rod instrumentation and Drummond wiring. We matched 14 patients who had had CDI by age and sex with 14 patients who had had either Harrington rod instrumentation (n = 5) or Drummond wiring (n = 9). Average lateral curve correction was significantly better with CDI than with the combination of the other systems (71.9% and 56.4%, respectively; P less than .01). Average rotational correction was studied using the methods of Mehta, and Nash and Moe; all patients having CDI showed a median rotational improvement of 30 degrees; 57% of the comparison group had minimal improvement (P less than .01). These results suggest that CDI may offer a significant alternative to the Harrington and Drummond spinal instrumentation systems in the surgical management of adolescent idiopathic scoliosis. PMID- 2305295 TI - Screening for glycosuria during pregnancy. AB - It is currently recommended that every pregnant woman have a blood glucose screening test for gestational diabetes at 24 to 28 weeks' gestation. Random urine samples are also tested for glucose at each prenatal visit. In 500 consecutive pregnant women, random urine glucose screening values from each prenatal visit were compared with a serum glucose test done at 28 weeks' gestation after ingestion of a 50 gm glucose-containing beverage. Twenty-two patients (4.4%) subsequently were identified as having gestational diabetes. Eighty-five (17%) had some degree of glycosuria, and 19 (3.8%) had severe glycosuria. Only six (27%) of the 22 women with gestational diabetes had any glycosuria. As a screening test for gestational diabetes, glycosuria had a 27% sensitivity and a positive predictive value of only 7.1%. Severe glycosuria, although increased in women with gestational diabetes (P = .0071), occurred in only 18% of cases. Detection of severe glycosuria before 24 weeks' gestation is an indication to do earlier blood glucose screening. After blood glucose screening is done, routinely screening the urine for glycosuria at each prenatal visit does not appear to be clinically useful. PMID- 2305297 TI - Trauma in the elderly: determinants of outcome. AB - Severity of injury, patient age and preexisting medical conditions, time from injury to treatment, and quality of care rendered are generally recognized as major determinants of outcome after trauma. In a retrospective review, we compared 456 elderly patients (age greater than or equal to 65 years) with traumatic injuries to 985 younger patients (age less than 65). We compared cause of injury, injury severity score (ISS), seven risk factors indicating preexisting disease, complications, length of stay, and mortality. Overall mortality was 6.0% for patients aged less than 65 years and 8.6% for those older than 65. The injury severity score at which the probability of death was 10% was 17.3 in the older group and 24.9 in the younger group. Factors associated with outcome included cause of trauma (P less than .001), ISS (P less than .001), and number of complication factors (P less than .01). Preexisting risk factors were not significantly associated with outcome. We conclude that trauma in the elderly causes higher mortality with less severe injury, and that the mortality is related to the cause and severity of the trauma and the number of complications, and not to pre-existing disease. Length of stay increases with the severity of injury, except in the severely injured, who die. PMID- 2305298 TI - Patient-initiated mobile mammography: analysis of the patients and the problems. AB - Patient initiation of mammographic screening is one method of increasing compliance with screening mammography guidelines. A low-cost screening project using a mobile van was developed at the University of Alabama at Birmingham. Analysis of the first 2,099 patients revealed that the participants were generally white (92%), more likely to have had a previous mammogram than the norm (33% in this study vs 19% in a 1986 Gallup survey), and relatively high-risk (30% having a breast cancer risk factor). The cancer detection rate was 6.2 per 1,000 women screened, with a biopsy rate of 1.3% and a positive predictive value of 48%. More than half the cancers detected were in situ lesions or invasive carcinomas smaller than 1 cm. Our results suggest that low-cost mobile mammographic screening can operate at appropriate levels of sensitivity and specificity and is well accepted by participants. Such projects require considerable preliminary planning, significant financial and time commitment by the physicians involved, and meticulous follow-up. A mammography management software system was developed to facilitate tracking of patients for routine and diagnostic follow-up studies and rapid communication of results. Although most follow-up studies and biopsies were done in the community, resistance in the medical community was significant and is perhaps the greatest impediment to such screening endeavors. PMID- 2305300 TI - Oropharyngeal function study: radiologic means of evaluating swallowing difficulty. AB - The oropharyngeal function study is a videotaped radiographic examination of the oropharynx and cervical esophagus used in patients who are at major risk for aspiration because of swallowing difficulty. Preceding the radiographic evaluation, the patient is assessed clinically by a swallowing therapist who attends the examination with the radiologist. Close cooperation between the therapist and radiologist better defines the specific swallowing problems, avoids inadvertent aspiration of large amounts of contrast material, and best directs proper management of the patient. We describe our cooperative approach to evaluating oropharyngeal dysphagia. PMID- 2305299 TI - Cancer mortality in the South, 1950 to 1980. AB - The overall cancer mortality for white and nonwhite men rose twice as rapidly in the South as in the rest of the nation, largely influenced by the rapid growth in lung cancer mortality among southern men in both race groups, and by the significant increase in prostate cancer mortality among southern, nonwhite men. Although the overall cancer mortality rate among white and nonwhite women in the South remained stable, the relative contributions of cervical and lung cancer changed considerably with time. The proportion of cancer deaths in southern women attributed to cervical cancer decreased by 50% while the proportion ascribed to lung cancer tripled. The South's cancer mortality experience differed substantially from that of the rest of the United States, which suggests that southerners diverge from residents of other parts of the United States in their risk of cancer, and in their access to and use of services for cancer prevention, diagnosis, and treatment. This study provides information for planning strategies for the reduction of cancer mortality in the South. PMID- 2305302 TI - As a matter of "fact"... PMID- 2305301 TI - Is there divine justice in AIDS? Why now, and not before? AB - Retroviruses emerged before Homo sapiens in the course of vertebrate evolution. The first human retrovirus was isolated in 1979; the human immunodeficiency virus (HIV-1) assumed epidemic importance in 1981. That such a novel threat to the survival of our species struck only when we had in place, for the first time, the science necessary to fight back seems remarkably coincidental. Cause-and-effect explanations include (1) human activities unique to the late 20th century and (2) a merciful, slow-to-anger God willing to "hold back" until the right time (chairos). By either possibility, AIDS might signify our failure to manage properly the world's ecosystems, the limitations of scientific progress, and/or deficiencies in our collective worldview. PMID- 2305303 TI - Business and managerial education in the medical school curriculum. AB - The need for medically related business and managerial training for medical students and physicians is an area of education that has been frequently discussed among physicians in private and academic practice. However, little has been done by physicians or in formal programs of medical or graduate medical education to address the need to introduce this type of training. This paper, based upon a survey of the medical students at Vanderbilt University, analyzes this need and proposes three new approaches in implementing medically related business and management education and training. PMID- 2305305 TI - "Ring around the artery" as a presenting feature in undiagnosed asthma with pneumomediastinum. AB - Acute bronchial asthma may be complicated by pneumomediastinum, often accompanied by the "ring around the artery" sign, described in association with asthma, trauma (gunshot wound), subclavian catheterization, and cocaine use, or with no identifiable risk factors. The diagnosis of pneumomediastinum should always be considered in an asthmatic patient with chest pain, cough, and dyspnea. Lateral chest film reveals a radiolucency outlining the right pulmonary artery. Such patients recover spontaneously with conservative therapy. PMID- 2305304 TI - Secondary bacterial peritonitis due to Listeria monocytogenes after paracentesis. AB - Although it is a relatively rare cause of peritonitis, Listeria monocytogenes must be considered in cirrhotic patients with ascites and a suggestive clinical presentation. We believe this is the first report of a case of peritonitis due to L monocytogenes in a patient without sepsis, and the sixth reported case of bacterial peritonitis in a patient with cirrhosis. PMID- 2305306 TI - Retrotracheal goiter. AB - Retrotracheal extension of a goiter, though rare usually causes respiratory compromise, dysphagia or vascular obstruction. We have described an asymptomatic patient with a large retrotracheal goiter resected via a collar incision. PMID- 2305307 TI - Survival after malignant pericardial effusion and cardiac tamponade in advanced ovarian cancer. AB - Malignant pericardial effusion and tamponade are rarely seen complications of epithelial ovarian cancer. With the use of multiagent chemotherapy these complications may be seen more frequently in the future. Therapy should be individualized, as long-term survival may be possible if the systemic manifestations of the cancer can be controlled. PMID- 2305308 TI - Electrocardiographic abnormalities after a transient ischemic attack. AB - I believe this is the first reported case of neurogenic ECG changes following a transient neurologic insult. The profound and long-lasting ECG changes that followed a brief neurologic derangement adds credence to the theory of actual myocardial damage as the genesis of neurogenic ECG changes. PMID- 2305309 TI - Unusual cause of traumatic diaphragmatic hernia in a 12-year-old boy. AB - A 12-year-old boy with a short history of dyspnea and occasional left-sided chest pain was discovered to have a diaphragmatic hernia that apparently resulted from minor chest trauma two years earlier. A large portion of the small bowel, part of the transverse colon, and the entire omentum were found in the left side of the chest. The patient recovered uneventfully after primary repair of the diaphragm. Although such lesions are usually associated with relatively severe injuries, this case shows that they may result from any type of chest trauma. PMID- 2305310 TI - Successful thrombolytic therapy for acute myocardial infarction in a renal transplant patient. PMID- 2305311 TI - Trigger point origin of musculoskeletal chest pain. PMID- 2305312 TI - A new intrathoracic foreign body. PMID- 2305314 TI - [3D reconstruction of planar sectional images using a small computer]. PMID- 2305313 TI - Long term trends in parasuicide and unemployment in Edinburgh, 1968-87. AB - Aggregate- and individual-level trends in parasuicide and unemployment among men and women resident in Edinburgh during the years 1968-87 are reported. During the first half of the period unemployment and parasuicide rates increased in parallel (r = 0.91, P less than 0.001 among men; r = 0.82, P less than 0.01 among women). However, while unemployment continued to rise after 1977, parasuicide rates tended to fall (r = -0.83, P less than 0.001 among men; r = -0.38, NS among women). It could be shown that the reversed relationship between parasuicide and unemployment after 1976 was not due to changes over time in the validity of the local unemployment rate as a marker of economic conditions. Suggested explanations for the falling parasuicide rate in Edinburgh include the possibility of a "threshold" effect and the influence of other (non-economic) factors. The rate of parasuicide among the unemployed fell, especially after 1973, while the rate among the employed rose until 1976-7, thereafter tending to fall. The relative risk (rate among the unemployed/rate among the employed) declined until 1979, since when it has fluctuated at about 10. The highest rate of parasuicide was consistently found among the long-term unemployed. PMID- 2305315 TI - Will baby get AIDS? First good test tells. PMID- 2305316 TI - Neurocysticercosis. PMID- 2305317 TI - Teenage pregnancy. PMID- 2305318 TI - [Abortion--ethical and legal implications important to the physician]. AB - The medical doctor's status within the South African juridical praxis of abortus provocatus is examined. A comparison is drawn between the situation in South Africa and that in the rest of the world. A cursory appraisal of the ontological status of the unborn in the Judeo-Christian tradition delineates ethical norms that do not perforce correspond with the abovementioned juridical praxis. The author attempts to answer the question whether the South African law concerning abortus provocatus is a good law. PMID- 2305319 TI - Clinical diagnosis of cardiac beriberi. AB - The clinical features of 28 patients with biochemically proven cardiac beriberi were prospectively studied. Patients recruited over a 2-year-period fell into two groups: (i) those with signs of hyperdynamic circulation; and (ii) those presenting with heart failure and circulatory shock with or without metabolic acidosis. All patients showed a dramatic response to intravenous thiamine; in group 1 the hyperdynamic state resolved within hours and in group 2 there was an immediate rise in the blood pressure with gradual resolution of the acidosis in 6 8 hours. Two patients in whom the diagnosis was missed died soon after admission to hospital. A notable finding was that even in the presence of peripheral circulatory shock, patients with beriberi had preservation of the femoral pulses often with 'pistol shots' and femoral bruit; this finding has clinical value in the diagnosis of acute cardiovascular beriberi (shoshin beriberi). PMID- 2305320 TI - Idiopathic acute myelopathy. AB - The clinical spectrum of acute intrinsic spinal cord disease remains uncertain because of varying criteria used in different studies. The characteristics of 17 patients with idiopathic acute myelopathy drawn from a larger group of 34 with acute intrinsic myelopathies of varying aetiology are reported. Results, which differ from previous studies, include the finding of a high proportion of patients with evidence of predominantly unilateral cord disease (47%). A higher percentage of patients (24%) than previously reported later developed multiple sclerosis, possibly related to broader inclusion criteria. A rise in protein concentration of the cerebrospinal fluid on repeat lumbar puncture was observed in patients with spinal shock on presentation, and a poor outcome was most clearly associated with these cases. PMID- 2305321 TI - Assessment of the nutritional status of infants and children with biliary atresia. AB - Since liver transplantation for children with end-stage liver disease has become accepted therapy clinicians have shown interest in the nutritional depletion that occurs with biliary atresia, since children with this condition form the largest group presenting for possible transplantation. Eleven infants and children with biliary atresia (age range 1,5 months-7 years) seen at the Red Cross War Memorial Children's Hospital over a 4-month period (March-June 1988) were studied. All but one had severe cholestasis at the time of the study. Nutrient intake during the hospitalised period was noted. Clinical nutritional parameters were documented and serum levels of vitamins A, D, E and the trace elements zinc and copper were measured. All patients with cholestasis (10/11) over 3 months of age (8/10) showed evidence of severe growth stunting, with weights below the 3rd percentile. Head circumference measurements were less than 5th percentile in 7/8 of those over 4 months of age including a 7-year-old child who had lost his jaundice after porto-enterostomy at age 2 months. All those with cholestasis showed evidence of fat-soluble vitamin deficiency and to a lesser extent zinc deficiency, but had raised serum copper levels. Three of 4 patients receiving cholestyramine had very low levels of vitamin E despite supplementation. These findings confirm the presence of severe nutritional depletion and growth stunting in patients with biliary atresia and the failure of 'normal' nutrient and vitamin supplementation to correct these deficiencies. The importance of close attention to nutrition in adequately preparing those patients assessed as suitable for liver transplantation therapy is stressed. PMID- 2305322 TI - Analgesics and gastric ulcers. A case-control study in an urbanised black population. AB - The patterns of analgesic ingestion in urbanised black patients with gastric ulcer disease were assessed. A strong statistical association was found between the quantity ingested and the disease. There was no difference in the type of analgesic and smoking and alcohol habits between gastric ulcer patients and controls in this study. PMID- 2305323 TI - Disturbed oesophageal motility after eradication of varices by chronic sclerotherapy--a scintigraphic study. AB - Oesophageal function after sclerotherapy for varices in 29 patients was compared with that in 15 patients with untreated varices using a scintigraphic technique. The first group had significantly longer transit times in each third and also in total time compared with a control group of 32 subjects (upper-third P = 0,02; middle-third P = 0,01; lower-third P = 0,0001; and total transit time P = 0,0001). Minor abnormalities of transit were found when the untreated group was compared with controls (increased total transit time P = 0,02). These results indicate that abnormalities of transit are increased after sclerotherapy for varices. PMID- 2305324 TI - Atherosclerosis--multi-organ involvement the rule rather than the exception. AB - Atherosclerosis is a systemic disorder and significant lesions often occur in organ systems other than the symptomatic area. Three groups of patients, those admitted to hospital with either coronary artery disease, carotid artery stenosis or peripheral vascular disease, were examined for concomitant atherosclerotic lesions. Non-invasive tests, namely duplex scanning of the carotid arteries, arm ergometer exercise testing, and segmental pressure of the limbs, were used during evaluation. A clear association between ischaemic heart disease, carotid artery stenosis and femoropopliteal disease was found. Women appear to be more prone to multi-organ involvement than men; their higher average age on admission to hospital is a possible explanation for this in some cases, but not all. PMID- 2305325 TI - Observations on early school failure in Zulu children. AB - The outcome of the screening of 2,190 children who had to repeat the school entry grades (Substandard A) in 25 junior primary schools in two KwaZulu townships is reported and the implications are discussed. The high number of repeaters did not appear to be due to an excess of mentally retarded children, the percentage being similar to that which could be expected in such a community world-wide. Difficulty in intelligence testing was experienced, but we describe how this was overcome by testing speed of learning. Visual defects, hearing defects and having no food before school accounted for the failure of many repeaters. Lack of preschool teaching by parents and schools and very strict discipline necessitated by large classes and a wide range in ages, which both led to anxiety on the part of the pupils, and sending children to school at too young an age were regarded as additional factors. Simple interventions were suggested to the school teachers; more than 1,000 pupils were followed up, with encouraging results. PMID- 2305326 TI - Hypertrophic cardiomyopathy in the black population of South Africa. PMID- 2305327 TI - Perinatal mortality in the black homelands. PMID- 2305328 TI - Poliomyelitis vaccine coverage in south-western Johannesburg. PMID- 2305329 TI - Jaundice as a sign of poor prognosis in Staphylococcus aureus septicaemia. PMID- 2305330 TI - Venospasm due to propofol after chemotherapy. PMID- 2305331 TI - Spread and persistence of infection with a trachoma biovar strain of Chlamydia trachomatis in multiplying and nonmultiplying McCoy cells. AB - The trachoma biovar of Chlamydia trachomatis enters host cells in culture with difficulty, and cell-to-cell spread resulting in amplification of the initial growth usually does not occur. An experimental model was devised to demonstrate that, by using conditions that more closely approximate those encountered in man, the trachoma biovar of C. trachomatis can readily achieve cell-to-cell passage. Fresh McCoy cells were sequentially added to monolayers that had been inoculated with a trachoma biovar strain of C. trachomatis 3, 6, and 9 days earlier. Subsequent incubation resulted in intercellular propagation, with an increase in the number of inclusions from 500 to 80,000 per coverslip. A second experiment demonstrated the reproducibility of this phenomenon and showed that cell-to-cell spread can occur at a low rate in overcrowded, not overlaid, cell layers; it also showed that, in multiplying cell layers, the infection tends to become persistent. PMID- 2305332 TI - Pivampicillin versus doxycycline in the treatment of chlamydial urethritis in men. AB - Pivampicillin and doxycycline were compared in the treatment of chlamydial urethritis in 80 heterosexual men. The trial was carried out in a double-blind, comparative parallel group fashion. Forty patients were treated with 700 mg of pivampicillin twice daily and another 40 with 200 mg of doxycycline on the first day and thereafter with 100 mg of doxycycline and one placebo tablet daily. Both treatments lasted for 9 days. Follow-up examinations were carried out 2 weeks (14 16 days) and 4 weeks (26-30 days) after the start of treatment. Altogether five (12.5%) of the forty pivampicillin-treated patients were clinical failures and three (7.5%) still harbored Chlamydia trachomatis after treatment. The corresponding figures for the doxycycline-treated patients were two (5.1%) and one (2.6%). The difference between the treatment results of the two groups did not reach statistical significance. PMID- 2305333 TI - Incidence of uncomplicated genital infections in women using oral contraception or an intrauterine device: a prospective study. AB - Over a period of 2 years, the authors prospectively followed a cohort of 123 women using an intrauterine device (IUD) and 108 women using oral contraception (OC) in one family practice. They found nine new episodes of cervical chlamydial infection in OC users (7/100 woman years (WY] as compared to 1 new episode in IUD users (0.8/100 WY), yielding a relative risk (RR) for OC users of 8.8 (95% confidence interval (CI): 1.3-59.0). During the 24 months of observation, 15% of OC and 2% of IUD users acquired at least one episode of Chlamydia trachomatis infection (P = .01). Bacterial vaginosis occurred more frequently in IUD users (25/100 WY) than in OC users (9/100 WY) (RR = 2.8; 95% CI: 1.5-5.1). During the 24-month period, 50% of women using an IUD had at least one episode of bacterial vaginosis, compared with 20% of the OC users (P = .001). Symptomatic bacterial vaginosis was associated with the use of an IUD (RR for IUD users was 7.7; 95% CI: 2.1-28.4), whereas asymptomatic bacterial vaginosis was associated with sexual promiscuity. PMID- 2305334 TI - Prevalence and epidemiologic correlates of Chlamydia trachomatis in rural and urban populations. AB - In two rural and two urban family planning clinics in central Pennsylvania, the authors screened 889 women making routine visits for Chlamydia trachomatis using the Chlamydiazyme immunoassay method (Abbott Laboratories; North Chicago, IL). C. trachomatis antigens were detected in 11.2% of the women; they found no differences in prevalence between rural and urban clinics. Among 21 clinical characteristics and seven risk factors, younger age (younger than 25), oral contraceptive use, gonococcal infection, mucopurulent exudate, abnormal vaginal discharge, and cervical ectropion were associated with chlamydial infection. Logistic regression revealed that age alone was independently associated with infection. The authors found that screening criteria derived from other epidemiologic studies generally did not predict the presence of C. trachomatis in the present sample. In a follow-up study performed at least one year later, 169 patients were re-screened; 47 tested positive and 122 negatives for C. trachomatis. Overall, 11.8% were infected, which was 12.4% of those who originally tested negative and 10.6% of those who originally tested positive. PMID- 2305336 TI - Vulvovaginal candidiasis complicating recurrent bacterial vaginosis. AB - In this study the authors reveal a high incidence of asymptomatic and symptomatic vulvovaginal yeast infection in patients with recurrent bacterial vaginosis. Symptomatic yeast vaginitis in these patients presents frequently as a mixed infection with symptoms and signs of both clinical entities being present simultaneously. The authors diagnosed vulvovaginal candidiasis in 10 (29%) out of 35 patients with a history of recurrent bacterial vaginosis; vulvovaginal candidiasis and bacterial vaginosis together were detected in 12 (34%) out of 35 women. Optimal therapeutic results usually require concomitant treatment of both candidal vaginitis and bacterial vaginosis. The lack of specificity of signs and symptoms of vaginitis mandates that women with recurrent bacterial vaginosis, for each symptomatic recurrence, be examined and evaluated by the use of simple laboratory tests to determine a specific diagnosis. Failure to appreciate the frequency of candida superinfection leads to empirical and inappropriate therapy for bacterial vaginosis. PMID- 2305338 TI - National expenditures on social security and health in selected countries. PMID- 2305335 TI - Contact tracing for human immunodeficiency virus (HIV) infection. AB - Contact tracing--or partner notification--is a generally accepted method for the control of sexually transmitted diseases (STDs), but its use as an epidemiological tool against the spread of acquired immunodeficiency syndrome (AIDS) has been questioned. The authors find contact tracing for infection with human immunodeficiency virus (HIV) quite feasible; it makes it possible for health care providers to reach people at high risk for infection in order to offer them counseling and testing. Contact tracing must be performed by someone directly engaged in caring for the HIV infected patient, as well as in giving support and aiding the patient through possible crisis reactions. Through this approach the authors were able to identify 188 contacts to 91 index patients. Thirty-eight of the contacts were seropositive for HIV infection, and 21 of these were previously unaware of their infection. PMID- 2305337 TI - Nongonococcal urethritis incidence has fallen at one university health service: are "safer sex" messages being heard? AB - The authors determined the incidence of nongonococcal urethritis (NGU) longitudinally in patients attending a university health service between August 1986, and May 1988. During this period, the authors observed a statistically significant fall in NGU incidence. This fall coincided with awareness of AIDS risks due to national and local media encouragement of condom use and avoidance of anonymous or promiscuous contacts. Although the authors have no evidence that these educational efforts resulted in the observed fall in NGU incidence, other examined, potentially intervening variables can not completely explain the observed changes. A fall in NGU incidence may be a marker for a more generally decreased risk of sexually transmitted diseases (STDs) in at least some men. PMID- 2305339 TI - Income change at retirement. AB - Less than one-fourth of SIPP retirees made the transition from full-time work and no benefit receipt to benefit receipt and no work during the 32 months of the 1984 SIPP panel, and these full retirees appear to differ economically from those who had not fully retired during the 32 months. Income declined to 60 percent of preretirement levels for those who received Social Security benefits and employer pensions, and to 46 percent for those who received only one type of benefit after ceasing full-time work. Family income cushioned the decline. About one-third of retirees had larger changes in income shortly before or after observed retirement transitions than right at the retirement transitions. Larger changes in income were associated with changing one's work effort. Asset income was quite variable across the entire panel. A monthly view of persons in various stages of retirement has brought into sharper focus than has previously been recognized the many paths into retirement, often over an extended period of time, during which status may change back and forth. A one-time or occasional extension of the SIPP to perhaps a 5-year period for the near-retirement-age population would increase the proportion of retirees for whom the full process is observed in such great detail. Alternatively, information on the timing of changes in labor-force and pension status may be collected in a proposed new Retirement History Study that calls for interviewing persons at 2-year intervals over a 10-year period for a more accurate picture of the retirement process. PMID- 2305340 TI - The accuracy of oral self-perceptions in a dentate older population. AB - A random sample of 1,016 subjects aged 65 and older were interviewed and examined in their own homes. The sample was stratified by race and place of residence. As part of the interview, the 821 dentate subjects were asked to rate their mouth appearance, chewing ability, and mouth health. Most subjects responded positively to these questions. The self-perception of mouth health was most related to the presence of anterior teeth. Perception of chewing ability was most related to the number of anterior teeth present, total number of teeth present, and the need for extractions. Subjects also were asked about their perceived dental needs. A small proportion of subjects thought they needed restorations, periodontal treatment, or teeth replacement. Subjects generally were not able to define the extent of their treatment needs, but their self-perceptions of mouth appearance, chewing ability, and mouth health had some relationship to their oral health. PMID- 2305341 TI - Objective evaluation of an airway management appliance in infants with craniofacial anomalies. AB - This study describes an intraoral appliance designed to reposition the tongue to facilitate a patent airway for infants experiencing respiratory distress. Transcutaneous pulse oximetry is used to objectively evaluate this method of airway management in 15 neonates with craniofacial anomalies. The appliance can significantly improve the blood oxygen saturation level in the infants in whom it is used (P less than .0001). PMID- 2305343 TI - Noninvasive diagnosis of vascular diseases. PMID- 2305342 TI - A comparison of the oral health of persons with and without chronic mental illness in community settings. AB - Severe dental disease has been reported for patients receiving psychiatric treatment. This study compared the oral status of noninstitutionalized adults with chronic mental illness with a similar group without such history, and evaluated relative risk factors, for example, xerostomia, diet, hygiene, and poverty. A sample of 37 subjects with chronic mental illness (CMI) and 29 control subjects without mental illness were assessed for dental, medical and social history; head, neck, and oral soft tissue pathology; salivary flow; DMFS, gingivitis, loss of periodontal attachment, plaque, and calculus. The groups were equivalent in socio-economic level, education, dental history, and home care. All subjects with CMI received psychotropic medications (mean of 3.8 drugs for 10.3 years). The CMI group had significantly higher incidence in the following variables: self-reported dry mouth; consumption of carbonated beverages (P less than .001); mucosal, lip, and tongue lesions (P less than .01); coronal smooth surface caries (P less than .001); severity of plaque (P less than .001) and calculus (P less than .01); and salivary flow (P less than .05). No significant differences were evident in the M and F components of DMFS, in gingivitis or loss of attachment. The results indicate significant increases in risk factors and increased oral pathosis in persons with mental illness who live in community settings compared with a control group that showed dental neglect. PMID- 2305344 TI - Retroperitoneal and peritoneal drainage and lavage in the treatment of severe necrotizing pancreatitis. AB - In severe necrotizing pancreatitis, the retroperitoneum is the main site both of autodigestion and of the production of toxins. With the aim of removing necrotic tissues and active enzymes from the retroperitoneum, we developed a surgical approach based on a wide exposure of the pancreas and on the insertion of multiple drainages with postoperative irrigations with hypertonic solutions and antiproteases. We treated 191 patients, and our results correlated with the timing of the operation. The operative mortality rate ranges from 8.1 in patients undergoing our procedure within 48 hours from the onset of the disease to 28.4 per cent when the operation was delayed for more than 96 hours. Our technique is detailed and the indications as to the timing of surgical treatment in instances of pancreatitis are discussed. PMID- 2305345 TI - The management of splenic trauma in the adult patient with blunt multiple injuries. AB - An analysis of 106 adult patients with blunt multiple organ injury and splenic trauma was carried out during an eight year period. Three groups were studied- group 1, splenectomy; group 2, splenorrhaphy, and group 3, observation. There was no statistically significant difference in initial blood pressure, pulse or hematocrit among the three groups. The mean injury severity score (ISS) was higher for those in groups 1 and 2 (26.8 and 25.6, respectively) versus patients in group 3 (17.9) (p). There were a total of 38 intra-abdominal injuries in 34 patients of which 21 required surgical repair. No patient in the nonoperative group required laparotomy for a missed associated intra-abdominal injury. There were a total of 15 intra-abdominal complications related to splenic management. In the observation group, seven patients ultimately required laparotomy for continued splenic bleeding. In the splenorrhaphy group, the complication rate was significantly lower versus the other two groups (p). We concluded that, if technically feasible, splenorrhaphy is a safe procedure in the multiply injured patient in the absence of hypotension and coagulopathy. Nonoperative management of blunt splenic trauma should be viewed with caution because of the high failure rate in the multiply injured patient. PMID- 2305346 TI - The Kiricuta procedure in reconstructive surgical treatment of the breast. AB - A series of 50 patients with carcinoma of the breast underwent omental transposition. This palliative procedure is indicated for recurrences after conservative treatment, radiation necrosis and Stage III or IV ulcerated tumors. The operative technique is described in detail. Omentoplasties were performed upon 33 right and 17 left mammary areas. Forty-five right pedicled flaps and only four left areas were used. One patient died on the fourth postoperative day because of massive pulmonary embolus. Local repair was satisfactory in 76 per cent of the patients. Four patients presented with herniation of the abdominal wall at the site of omental tunneling. In three, the treatment consisted of sectioning the vascular pedicle and reinforcing the parietal closure with Dacron (polyester fiber) mesh. PMID- 2305347 TI - Heller-Belsey and Heller-Nissen operations for achalasia of the esophagus. AB - From 1972 to 1985, 101 consecutive patients underwent Heller's myotomy and Belsey repair (H + B) (n = 43) or Nissen fundoplication (H + N) (n = 58) for achalasia of the esophagus. There was no operative mortality after either operation; minor pulmonary complications occurred after H + B procedure in 9.3 per cent of the patients. Good to excellent long term results were achieved in 87 per cent of the patients after H + B repair and 83 per cent of the patients undergoing H + N. The failure rates were 2.5 and 11.3 per cent, respectively. The analyses of postoperative esophageal symptoms showed that the incidence of heartburn was greater after H + B repair and the incidence of obstructive symptoms was greater after H + N. The inability to vomit or belch, or both, was 10.2 per cent in the H + B group and 13.1 per cent in the H + N group. Finally, 56.4 per cent of patients after H + B repair and 41.0 per cent of those after myotomy and H + N were considered to be cured after the operative procedure was performed. Patients were improved in 41.0 and 47.3 per cent, respectively. PMID- 2305349 TI - Open treatment with drainage for ingrowing toenail. AB - As a radical treatment of ingrowing toenail, labiomatricetomy is accepted among plastic surgeons. However, postoperative hematoma or infection, or both, is the problem when sutures are placed between the nail and nail fold. We have added a drainage procedure to the standard labiomatricectomy, which can be done on an outpatient basis. Ninety-eight patients were observed during a six month period. Three patients who had had steroid therapy had suppuration postoperatively, while all of the other patients had an uneventful recovery period. Recurrence was seen in three patients who suffered from onychogryposis, which may require some other method of treatment. Complications were seen in early instances, three inclusion cysts with infection and three nail spikes. Technical error caused these complications, and these have disappeared with the use of this technique. PMID- 2305348 TI - In vivo comparison of inhibition with proglumide and CR-1409 of cholecystokinin induced pressure in the biliary tract of the guinea pig. AB - This study was done to compare the effects of two cholecystokinin antagonists, proglumide and CR-1409, on cholecystokinin-induced changes in intrabiliary pressure in vivo. We have substantially modified the constant infusion biliary manometry model, successfully used in large animals, to measure contractility of the gallbladder in guinea pigs. A silicone catheter for manometry was placed in the fundus of the gallbladder of an anesthetized guinea pig, and the biliary tree was constantly infused at 0.1 milliliter per minute with normal saline solution. The intraluminal pressure of the system was continuously recorded. The model was used to demonstrate a dose-response curve to bolus administration of exogenous cholecystokinin (0.01 to 1.0 nanomole per kilogram) and also to study the actions of proglumide, an antagonist to gastrin and cholecystokinin, and CR-1409, a newer, specific cholecystokinin antagonist, on cholecystokinin-induced contraction of the gallbladder of the guinea pig in vivo. Proglumide, at a dose of 5 millimoles per kilogram, completely abolished increases in intrabiliary pressure caused by cholecystokinin (0.5 nanomole per kilogram), whereas this effect was achieved by only 5 micromoles per kilogram of CR-1409. In both, there was full recovery from cholecystokinin antagonism within one hour. CR-1409 is one thousand times more potent than proglumide against cholecystokinin-induced changes in intrabiliary pressure in vivo and appears to be a useful pharmacologic reagent to study cholecystokinin-mediated components of physiologic contraction of the gallbladder. PMID- 2305350 TI - Evolution in the management of splenic injury in children. AB - To assess the changes in the management of splenic trauma, the charts of all patients with splenic injury, documented either roentgenographically or at operation, treated at the Childrens Hospital of Los Angeles from 1965 through 1985 were reviewed. One hundred and eleven patients with confirmed splenic injury were treated. Forty-one patients were seen during the first decade (1965 to 1975) and 70 during the second decade (1976 to 1985). The majority of patients were boys with a mean age of seven years. All of the patients sustained blunt abdominal trauma. During the first decade, all of the patients who had a recognized splenic injury underwent splenectomy. In the second decade, 44 patients were treated without surgical intervention. Twenty-six of the patients required surgical treatment. Splenorrhaphy was successful in 15; however, splenectomy was required in 11 patients. The patients who required surgical therapy had more complications and required more blood products than those patients who were treated nonsurgically. The overall survival rate was 95 per cent and was similar in both decades. Associated injuries, not the splenic injury, were responsible for the lethal outcome of the nonsurvivors. Although the majority of children with splenic injury can be managed nonoperatively, surgical intervention continues to be necessary in our experience in approximately 38 per cent of the patients with an over-all splenic salvage rate of 85 per cent. PMID- 2305351 TI - A simple technique of T-tube insertion in transplantation of the liver. PMID- 2305352 TI - En bloc resection of hepatic segments 4B, 5 and 6 by transverse hepatectomy. PMID- 2305353 TI - A simple method to remove a defective urinary catheter. PMID- 2305354 TI - Preoperative assessment of the length of the stomach for esophageal substitution. AB - This method is easily applied and useful for the estimation of the actual length of the gastric tube in situations of reconstruction after subtotal esophagectomy. The actual length of the gastric tube was almost identical to that of the stomach which was measured from the preoperative roentgenogram. In the end, a safe reconstruction by this approach will decrease the operative mortality rate caused by the leakage of the anastomosis. PMID- 2305355 TI - Interface between the meningioma and the brain on magnetic resonance imaging. AB - Magnetic resonance imaging of 31 meningiomas in 29 patients was retrospectively reviewed and compared with pathologic specimens in 25 tumors to investigate how magnetic resonance imaging could delineate a tumor-brain interface. The thick, collagenous connective tissue, which was seen around four tumors, was shown as a low signal intensity rim on both a T1-weighted image and a T2-weighted image. A rim of low signal intensity on a T1-weighted image and high signal intensity on a T2-weighted image most likely represented cerebrospinal fluid space: this finding was seen around eight tumors. No distinct rim could be identified in five tumors. Of these five, two tumors grew invasively into the brain. Although mixed features predominated in meningiomas, magnetic resonance imaging could well delineate a tumor-brain relationship in most of the cases. PMID- 2305356 TI - Ruptured intracranial aneurysms: an autopsy study of 133 patients. AB - The autopsy findings of 133 patients with ruptured intracranial aneurysms were reviewed: 24 (18%) had multiple aneurysms. Intraventricular hemorrhage was seen in 53 patients (40%), and intracerebral hematoma was seen in 52 (39%). Intraventricular hemorrhage was seen most frequently in patients with anterior communicating artery aneurysms [21 of 40 (53%)]. Intracerebral hematoma occurred most frequently in patients with middle cerebral artery aneurysms [11 of 28 (39%)]. Hemorrhages arising from anterior communicating artery aneurysms had two types of penetration routes into the lateral ventricle. The first was through the inferomedial portion of the frontal lobe, and the second was through the corpus callosum. The second type was poorly visualized in horizontal sections of the brain. Of 40 patients with anterior communicating artery aneurysms, the first type of penetration route was observed in 15, and the second type was found in 3. The second type is rare, and if the hemorrhage is not massive, it may be overlooked in axial computed tomography scans. Of the 109 ruptured aneurysms, 18 (17%) were 4 mm or less in diameter, 50 (46%) were 5-9 mm in diameter, and 41 (38%) were 10 mm or larger in diameter. In the 21 patients with multiple aneurysms, unruptured aneurysms were smaller than ruptured aneurysms in 17 of 27 (63%), equal size in 9 (33%), and larger in 1 (4%). Regarding rerupture, the larger the ruptured aneurysms were, the higher the percentage of rerupture, that is, 11% of 18 ruptured aneurysms of 4 mm or less in diameter, 32% of 50 of 5-9 mm in diameter, and 37% of 41 of 10 mm or larger in diameter had reruptured. It seems that the larger the size of the aneurysm, the higher the risk of rerupture as well as of initial rupture. PMID- 2305357 TI - Primary spinal intramedullary malignant lymphoma. A case report. AB - A rare case of primary malignant intramedullary lymphoma, localized in the cervical part of the spinal cord, is presented. The onset of clinical symptoms was associated with herpes zoster infection. Surgery led to the histological diagnosis. The clinical investigations excluded the presence of lymphoma in other sites in the central nervous system and in the extraneural organs. Postoperative irradiation and chemotherapy effected relict of neurological symptoms. PMID- 2305358 TI - False aneurysm of the cavernous carotid artery: a complication of transsphenoidal surgery. AB - Although excellent results currently are being achieved with transsphenoidal surgery, life-threatening complications may occasionally result from this approach. We present a patient with carotid injury sustained during transsphenoidal surgery, who presented 6 weeks postoperatively with a large false aneurysm in the cavernous part of the right internal carotid artery. This lesion was successfully treated by trapping. The pathogenesis of this complication is discussed and the relevant literature is reviewed. PMID- 2305359 TI - Cranial fasciitis of childhood with reactive periostitis. AB - We report a rare case of cranial fasciitis in an 11-year-old girl. The patient was found to have an ossifying soft tissue mass over the occiput that was arising from the cranial periosteum and the deep fascial layer. An associated florid periosteal reaction was found in the occipital bone adjacent to the scalp mass. The computed tomography and histologic pattern of this unusual lesion are discussed. A brief review of the literature is included emphasizing the need to investigate further this completely benign lesion that frequently is confused with a malignant neoplasm. PMID- 2305360 TI - A view from Europe: subspecialization in neurosurgery. PMID- 2305361 TI - Glasgow, Scotland as "one of the backwaters of the world". PMID- 2305362 TI - Rupture of an intracranial aneurysm. PMID- 2305363 TI - McKenzie reservoir. PMID- 2305364 TI - Adult aqueductal stenosis representing with double incontinence. PMID- 2305365 TI - Significance of preserving bridging veins in an interhemispheric approach. PMID- 2305367 TI - 1990--our bicentennial census. PMID- 2305366 TI - Relation of regional cerebral blood flow to hemiparesis in chronic subdural hematoma. AB - To investigate the causative mechanism of hemiparesis in chronic subdural hematoma, 38 patients with unilateral chronic subdural hematoma were studied on the relationship between their clinical manifestations and regional cerebral blood flow measured with 133xenon inhalation (16 detectors on each side of the head, Initial Slope Index). Twenty-five patients with hemiparesis (hemiparesis group) and 13 patients with headaches only and without any neurological deficits (headache group) were examined before surgery for chronic subdural hematoma. Among the hemiparesis patients, 15 were examined after surgery. Preoperative regional cerebral blood flow values in the headache group were normal in all regions bilaterally and showed no significant regional difference in one hemisphere or interhemispheric difference between the corresponding regions in both hemispheres, whereas preoperative regional cerebral blood flow values in the hemiparesis group were generally around the lower limit of the age-matched normal value and were subnormal in some areas, and the regional cerebral blood flow values were significantly lower on the hematoma side than on the intact side in most regions. The rolandic region especially showed the lowest regional cerebral blood flow value of 32.3 in the Initial Slope Index on average and the most significant interhemispheric differences of regional cerebral blood flow. Such a preoperative reduction of regional cerebral blood flow in the hemiparesis group normalized along with clinical improvement after evacuation of the hematoma. It was suggested that localized cerebral blood flow reduction at the rolandic cortical region under the hematoma might be one of the causative factors of hemiparesis in chronic subdural hematoma. PMID- 2305368 TI - Hepatitis B in the United States. 1988 update. PMID- 2305369 TI - Mortality from leading types of accidents 1976-77 and 1986-87. PMID- 2305370 TI - Embryotoxic effects of sodium arsenite and sodium arsenate on mouse embryos in culture. AB - Embryotoxic effects of two inorganic arsenic compounds, sodium arsenite (Asi) and sodium arsenate (Asa), on the development of mouse embryos during early organogenesis were studied using the whole embryo culture technique. Embryos with three to five somites exposed to 1-40 microM Asi or to 10-400 microM Asa were cultured for 48 hours and their development was compared with that of control embryos. Asi proved to be teratogenic between 3 and 4 microM and embryolethal at higher concentrations; Asa had similar activity but at concentrations ten times higher than for Asi. Both compounds produced a growth retardation and a similar pattern of defects. Growth retardation was indicated by a statistically significant reduction in crown-rump length, head length, and yolk sac diameter. Abnormal embryos were characterized by hypoplasia of the prosencephalon with open neural tube, hydropericardium, somite abnormalities, and failure of development of limb buds and sensory placodes. These results confirm that both Asa and Asi are embryotoxic compounds and that the Asi activity occurs at concentrations ten times lower than for Asa. Our results suggest that in humans both of these compounds may be involved in part of "unaccountable" early abortions and malformations claimed to be due to the toxicity of heavy metals. PMID- 2305371 TI - Congenital malformations in rats with the semilethal mutation fused pulmonary lobes. AB - It has been demonstrated that an autosomal recessive gene, fused pulmonary lobes (fpl), causes fusion of the right pulmonary lobes with several associated malformations and a high incidence of death in homozygous newborns (Aoyama et al. Teratology 1988; 37:159-166). The aim of the present study was to investigate whether the deaths of fpl/fpl newborns were caused by functional abnormalities of the malformed lung or other associated malformations. Day-20 fpl/fpl and fpl/+ fetuses were weighed and examined for gross abnormalities. The lungs of selected fetuses were further examined for histological abnormalities. A wide variety of associated external, visceral, and skeletal anomalies as well as relatively lower body weights than those of phenotypically normal fpl/+ littermates were observed in the fpl/fpl fetuses. The associated anomalies consisted of hematomas and/or subcutaneous hemorrhages in the head, truncus and limbs, eyelid anomalies, CNS defects, lobation anomalies of the liver, hypoplasia of the spleen, partial absence of the skull bones, and dorsi- or ventriflexion of the phalanges of the limbs. Among them, CNS defects and partial absence of the skull bones were considered to be possible causes of newborn deaths. However, the incidence of these malformations was approximately 10% and was lower than the neonatal mortality, which had been estimated to be approximately 50% in the previous study (Aoyama et al. Teratology 1988; 37:159-166). The lungs of fpl/fpl fetuses consistently had hypoplasia of the intermediate lobe and fusion of the right pulmonary lobes. No histological changes suggesting postnatal respiratory insufficiency were found in the lungs of day-20 fpl/fpl fetuses, and the cause of newborn death remains unclear. PMID- 2305372 TI - Amelia: incidence and associated defects in a large population. AB - Amelia, or complete absence of a limb, is a very rare congenital anomaly. The incidence of amelia in a population of 1,213,913 consecutive livebirths in British Columbia during the period 1952-1984 was studied using the records of a population-based registry with multiple sources of ascertainment. There were 18 cases of amelia, giving a minimal incidence rate of 0.15 per 10,000 livebirths for this birth defect. Amelia occurred equally frequently in upper and lower limbs, and 11 of 18 (61%) liveborn cases also had malformations of other organ systems. In the group with lower limb amelia a specific pattern of associated malformations, which included omphalocele and diaphragmatic defects, was identified. There was no evidence for familial recurrence of amelia. Conditions to be considered in differential diagnosis are discussed. PMID- 2305374 TI - Structure-activity relationships in the developmental toxicity of substituted phenols: in vivo effects. AB - Hansch analysis, a quantitative approach relating the physical-chemical properties of molecules to biological effects, was applied to a series of substituted phenols tested for developmental toxicity. The physical-chemical properties included a hydrophobic parameter (log P), an electronic parameter (Hammett sigma), and a bulk parameter (molar refractivity (MR]. Biological activities (potencies) were obtained for 27 congeners in a Chernoff/Kavlock Assay performed in Sprague-Dawley rats exposed on day 11 of gestation. The potencies discussed in this report are the following: the dose to decrease maternal weight gain by 10 g at 24 and 72 hours after treatment (MTOX1 and MTOX2); the dose to increase postimplantation loss by 1 over the concurrent control value (PLOSS); and the dose required to decrease total litter weight by 10% on postnatal day 6 (BIO6). A quantitative structure-activity relationship QSAR was developed for the maternal data (1/MTOX1 = (0.0344*log P) + (-0.1503*sigma) + 0.1195; n = 22, r = 0.81, P less than .0001), which related increasing lipophilicity and decreasing electron-withdrawing ability of the substituent on 22 para-phenols to increasing toxicity. Another QSAR was developed from eight para-phenols that had the greatest postimplantation loss potencies (i.e., less than 100 mmol/kg). The model (1/PLOSS = (-0.2676*log P) + (-0.1827*sigma) + (0.0265*MR) + 0.4420; n = 8, r = 0.93, P less than .0298) related decreasing lipophilicity and electron withdrawing ability and increasing bulk properties to the decreased viability of implantation sites. However, no descriptor was identified that distinguished the more potent from the less potent congeners for postimplantation loss, and no QSAR was found for litter weight on postnatal day 6 (even when limiting the analysis to the more potent congeners). Congeners were also grouped on a qualitative level according to whether they induced a biological effect below a dose of 6 mmol/kg (termed active), between 6 and 11 mmol/kg (moderately active), or greater than 11 mmol/kg (inactive). Overall, 14 of 27 congeners were classified as active in terms of maternal effects, but only 50% of these were active for developmental effects. Seven of the nine overall active developmental toxicants were active maternal toxicants. Four of the developmental toxicants produced a syndrome of effects that may be related to a similar mechanism of action or common metabolic pathway. Thus, from both quantitative and qualitative viewpoints, the properties of these phenolic congeners that promote maternal toxicity are different from those that contribute to developmental toxicity. It is therefore likely that the mechanisms of toxicity behind these effects are also different. PMID- 2305373 TI - Lack of lead effects on fetal development and offspring learning when combined with alcohol in the Long-Evans rat. AB - Two studies were conducted to evaluate the interactive effects of alcohol and lead during pregnancy in rats. Our purpose was to see if lead, as lead acetate, would influence the alcohol effect already known to exist. In the first study, pregnant Long-Evans rats received lead (as lead acetate), alcohol (20% w/v), or lead plus alcohol once a day on gestation days (GD) 10-20. On GD 20, when animals were sacrificed, mean blood alcohol levels were consistently higher for the lead plus-alcohol-dosed groups compared to alcohol alone, but these two groups did not differ in maternal weight gain, percent resorptions, litter size, or fetal weight. Mean blood lead levels were not consistently higher in the lead-plus alcohol groups compared to lead only, but the lead-plus-alcohol groups differed significantly from the lead-only groups at higher doses in the previously mentioned parameters. The lead-only groups did not differ from vehicle controls in any parameter in spite of blood lead levels as high as 300 micrograms/dl. In the second experiment, animals given a combination of alcohol and lead did not differ in activity, passive avoidance, or active avoidance learning compared to animals given alcohol or lead alone. Animals given lead only or the combination of lead plus alcohol had longer first trial latencies in the passive avoidance test. The data indicate that neither lead nor alcohol attenuates or potentiates each other's effects on reproduction or learning behavior in the Long-Evans rat even at high blood lead levels. PMID- 2305375 TI - Effects of TCDD on embryonic ureteric epithelial EGF receptor expression and cell proliferation. AB - The potent toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, producing hydronephrosis and cleft palate. Because of the long half-life of TCDD, the urinary tract is exposed throughout development after a single dose on gestation day (GD) 10 or earlier. TCDD-induced hydronephrosis is a consequence of occlusion of the ureter by epithelial cells. Since embryonic growth factors and the epidermal growth factor (EGF) receptor are probably involved in regulation of embryonic cell proliferation, this study examines the effects of TCDD on expression of EGF receptors and proliferation of ureteric epithelial cells in vivo and in culture. After exposure to TCDD by gavage (12, 24, or 30 micrograms/kg on GD 10; 6 or 24 micrograms/kg on GD 12) the mean cell depth of the ureteric and bladder epithelia was increased. EGF receptors were detected immunohistochemically in sectioned urinary tracts. The expression of receptors decreased with advancing development in control ureteric epithelia. However, after TCDD exposure the level of EGF receptors failed to decline. The incorporation of 3H-TdR was observed in sections by autoradiography, and after exposure to TCDD more epithelial cells showed incorporation than was apparent in controls. Transmission electron microscopy (TEM) of embryonic ureters from fetuses exposed to TCDD in vivo showed no cytotoxicity in basal cells and the cells remained undifferentiated, as in controls. Ureters taken from GD 12 embryos and cultured with 1 x 10(-10)M TCDD showed ureteric epithelial hyperplasia without cytotoxicity, but at 1 x 10(-8)M TCDD evidence of cytotoxicity was observed by TEM. The levels of TCDD found in fetuses after in vivo exposure (204 307 pg/fetus, with 1-2 pg in the urinary tract) compare well with the in vitro level (32 pg/ml), which was most effective in producing hyperplasia of the epithelial cells. The present study correlates a TCDD-induced increase in cell depth with altered regulation of EGF receptors and excessive proliferation, both in vivo and in cultured embryonic ureters. PMID- 2305376 TI - Deposition of low dose benzo(a)pyrene into fetal tissue: influence of protein binding. AB - The influence of maternal binding of benzo(a)pyrene (BaP) on its disposition into fetal tissue was investigated in pregnant Swiss-Webster mice. Low doses (10 ng/mouse) of radiolabeled BaP were administered by intravenous injection on day 15 of gestation. BaP was administered along with normal rabbit serum (NRS) (low binding paradigm) or anti-BaP antiserum (high binding paradigm) and animals killed at various time points. Total radioactivity in the fetus increased with time to peak concentrations in whole fetal homogenates at 12 hours. In contrast, maternal serum, liver, and lung showed a decrease in total radioactivity over the same time period. Total radioactivity/gram of fetal tissue was significantly higher in NRS-treated animals compared to anti-BaP-antiserum-treated animals. Since the levels of the parent compound, BaP, in fetal tissue fell over time similar to maternal liver and lung, the increase in total radioactivity in the fetus was due to an increased concentration of a BaP metabolite fraction in both the low binding and high binding groups. Significantly, a lower level of this metabolite fraction was found in fetal tissue from the anti-BaP-antiserum-treated animals. The present study shows that maternal exposure to this environmental pollutant, even at low doses, results in an accumulation of a metabolite-rich fraction in the fetal compartment, which may contribute to the teratogenic potential of BaP. The data also demonstrate that the amount of this accumulation can be diminished by increasing maternal binding proteins, such as by treatment with anti-BaP antiserum. PMID- 2305377 TI - Influence of maternal dietary zinc intake on in vitro tubulin polymerization in fetal rat brain. AB - The hypothesis that one of the biochemical lesions underlying zinc deficiency induced teratogenicity is altered microtubule formation was tested. Day 19 fetuses from zinc-deficient Sprague-Dawley dams were characterized by low brain supernate zinc concentrations and slow brain tubulin polymerization rates compared to controls. Brain supernate tubulin and protein concentrations were similar in zinc-deficient and control fetuses. In vitro brain tubulin polymerization rates were increased following addition of zinc to either control or zinc-deficient brain supernates; however, the stimulatory effect of added zinc on polymerization was significantly higher in brain supernates obtained from zinc deficient fetuses compared to controls. These results support the idea that one effect of fetal zinc deficiency is a reduction in tubulin polymerization, which in turn may result in altered microtubule function. PMID- 2305378 TI - [Consequences of free trade in live animals]. PMID- 2305379 TI - [Consequences of free trade in food stuff of animal origin]. PMID- 2305380 TI - [Registration and distribution of veterinary drugs up to and after 1992]. PMID- 2305382 TI - [Development of a vaccine against AIDS: some bright spots]. PMID- 2305381 TI - [Rhodococcus equi infection in a goat]. AB - Enterotoxaemia caused by Clostridium perfringens was diagnosed in a goat affected with severe enteritis which was found to be present at autopsy. Lesions bearing a resemblance to tuberculosis, caused by a Rhodococcus equi infection, were observed in the liver and lungs. This bacterium is constantly isolated from pulmonary abscesses in foals affected with pyemia. Similar cases of infection in goats were previously reported in the literature. PMID- 2305383 TI - [Agricultural policy up to and after 1992]. PMID- 2305384 TI - [Hip dysplasia: the triple pelvic osteotomy]. PMID- 2305386 TI - [Results of a survey of the functioning of veterinary practices]. PMID- 2305385 TI - [Arthroluxyl, information first!]. PMID- 2305387 TI - [From the Veterinary Chief Inspection for Public Health--Action Program Salbutamol (A beta agonist)]. PMID- 2305388 TI - [Veterinary drugs and good veterinary practice]. AB - The following definition of 'Good Veterinary Practice' in relation to pharmacotherapy is presented: 'The selective use (in accordance with directions for users) of veterinary drugs registered by the authorities in those indications in which they are permitted when the diagnosis has been established and in which the problem of residues in foods of animal origin on using these agents has been taken into account'. The following recommendations are made with reference to 'Good Principles of Veterinary Practice': (1) Current training and supplementary training in the fields of pharmacy and pharmacotherapy should be adjusted in the light of recent developments in society. (2) The development of simple, rapid and reliable tests for the detection of pathogenic agents and residues of veterinary drugs should stimulated. (3) The development of conveniently arranged and standardised data sheets in generally comprehensible terms should receive sufficient attention. (4) Quality control, particularly of generic products, deserves adequate attention. (5) The institution of a Side-Effects of Veterinary Drugs Office, in which the authorities, manufacturers and other parties concerned co-operate closely, is eminently desirable. (6) The establishment of a Veterinary Drugs Committee in which all interested parties are represented, is of the utmost importance within the framework of recommendations on policy to the authorities. PMID- 2305390 TI - [Will the veterinarian still have a pharmacy after/towards 1992?]. PMID- 2305389 TI - [Mycobacteriosis and inspection regulations]. PMID- 2305391 TI - [Dictyocaulus species, lungworms in cattle and deer in The Netherlands]. AB - Using recent descriptions of Dictyocaulus species, all samples of lungworms in cattle were identified as D. viviparus, and all samples from roe deer, red deer and reindeer being identified as D. eckerti by the present authors. Although cross infections between cattle and cervids are reported in the literature, these are not readily established. Because of the different species and the small likelihood of cross infections cattle and cervids are not regarded as serious sources of lungworm infections for each other. As the description of D. noerneri is based on very scanty information and it is not entirely impossible that it could have been D. viviparus, it is regarded as a species inquirenda. The correct name of the large lungworm of cervids is D. eckerti. PMID- 2305392 TI - [Bovine spongiform encephalopathy (BSE), a renewed appeal]. PMID- 2305393 TI - [Roentgen photos. No right to take along]. PMID- 2305395 TI - HLA antigens in Japanese patients with central nervous system lupus. PMID- 2305394 TI - Nomenclature for factors of the HLA system, 1989. PMID- 2305396 TI - Risk factors for stroke in middle-aged men in Goteborg, Sweden. AB - To evaluate stroke risk factors in Goteborg, Sweden, during 1970-1973 a cohort of 7,495 participating men from a general population sample of 9,998 men aged 47-55 years were examined with respect to cardiovascular risk factors. Men with hypertension and hypercholesterolemia and men who were heavy smokers were treated. We assessed stroke end points and cause-specific mortality using a stroke register and death certificates. During a mean follow-up of 11.8 years, 230 strokes occurred in the entire population sample (participants and nonparticipants) (7% subarachnoid hemorrhages, 13% intracerebral hemorrhages, 42% cerebral infarctions, and 38% unspecified strokes). Using univariate analysis, we found measured high blood pressure (systolic and diastolic), smoking, known hypertension, diabetes mellitus, stroke in either parent, severe psychological stress, marital status, atrial fibrillation, previous transient ischemic attacks, previous myocardial infarction, effort-induced chest pain, and intermittent claudication to be significantly related to all stroke. Of the stroke types, subarachnoid hemorrhage was not related to any of these indicators, and intracerebral hemorrhage was related only to measured high blood pressure. Using multivariate analyses, we found measured high blood pressure, smoking, and severe psychological stress as well as atrial fibrillation, previous transient ischemic attacks, and intermittent claudication to be independent risk factors for nonhemorrhagic stroke. Serum cholesterol concentration, occupational and leisure time physical activity, body mass index, alcohol abuse, and low occupational class were not risk factors for stroke. PMID- 2305397 TI - Cerebrovascular disease in Hong Kong Chinese. AB - Our prospective study of cerebrovascular disease in Hong Kong confirms a previous clinical impression that stroke in the Chinese has a pattern different from that in Caucasians. We studied 540 patients (aged 20-70 years) with stroke. Computed tomography or autopsy was obtained in 86.1% and showed an increase in the proportion with lacunar infarction, striatocapsular infarction, and parenchymal hemorrhage relative to the frequencies in Caucasians. This increase in the incidence of cerebral hemorrhage occurs not only in semicomatose and comatose patients but also in alert patients (16.9%) and those with a lacunar syndrome (12.5%). Our findings suggest that cerebrovascular disease in the Chinese selectively affects small vessels, causing lacunes and hemorrhages. In future community studies on stroke prevalence, researchers should be cautious about interpreting similar prevalence rates as reflecting similar risk factors or pathologies. PMID- 2305398 TI - Outcome after stroke in patients discharged to independent living. AB - In a prospective, population-based study, we evaluated rehabilitation outcome, place of residence, and functional ability 3, 6, and 12 months after stroke onset in 129 consecutive patients discharged from the hospital to independent living, either in their own homes or in an old people's home. The study group comprised 50% of all patients admitted for acute stroke between February 1, 1986, and January 31, 1987. Of the 129 patients, 125 returned to their own homes and four moved into an old people's home. Once they returned home, only minor changes occurred in the patients' place of residence or functional capacity. The majority of the patients (90%) were still living in their own homes after 12 months; 99% could walk independently indoors, 92-95% could climb a staircase, and 90% could manage their daily hygiene. Eight patients (6%) died during follow-up, and one fourth of the patients were hospitalized again. The average number of days of rehospitalization during the 12 months was 23. Our study may serve as a guide to the planning of stroke programs and to a more effective and efficient use of available health resources. PMID- 2305399 TI - Efficiency, effectiveness, and duration of stroke rehabilitation. AB - This prospective multicenter study identifies the variables significant in the prediction of rehabilitation efficiency, achievement of rehabilitation potential and duration of rehabilitation stay in 258 persons with a first stroke admitted to comprehensive inpatient rehabilitation in Brisbane, Australia, during 1984. All three dependent variables were poorly predicted, with only 17% of the variance in rehabilitation efficiency, only 30% of the variance in achievement of rehabilitation potential, and only 22% of the variance in duration of rehabilitation stay explained. Unlike other reports, we considered most of the major medical (side of paralysis, stroke etiology, site of the lesion, arterial distribution affected, etc.), rehabilitative (initial Barthel Index score, interval from stroke onset to acute-care hospital admission, interval from hospital admission to rehabilitation commencement, neurologic measures, etc.), and demographic (age, years of education, occupation, ethnicity, etc.) variables. The high proportion of unexplained variance is likely to be due to nonmedical factors influencing the selection of patients for rehabilitation. PMID- 2305400 TI - Arm and leg paresis as outcome predictors in stroke rehabilitation. AB - I used leg and arm paresis to predict outcome measured as extremity function in a prospective study of 75 consecutive hemiplegic patients admitted to an inpatient stroke rehabilitation unit. In each patient, extremity paresis was quantified according to the five-point scoring system advised by the Medical Research Council, upper extremity function was quantified using the Barthel Index subscore for feeding and dressing the upper body, and lower extremity function was quantified according to a five-point scoring of the ability to walk. Improvement was recorded for upper extremity function in 52% of the patients and for lower extremity function in 89%. Best extremity function was reached a mean +/- SEM of 9 +/- 3 and 10 +/- 4 weeks after stroke for the upper and lower extremities, respectively. In patients experiencing complete recovery, this occurred a mean +/ SEM of 7 +/- 2 weeks (for both upper and lower extremities) after the stroke. Only 8-11% of the patients with paresis scores of less than or equal to 2 regained independent extremity function after rehabilitation. Half of the patients with paresis scores of greater than or equal to 3 regained independent extremity function after rehabilitation, while the other half were able to perform extremity function with only minimal assistance. As predictors of extremity function, the Barthel Index subscore was slightly better (r = 0.64) than paresis score (r = 0.58). However, because evaluation of extremity paresis is easy, it appears to be useful as a preliminary predictor of outcome following stroke. PMID- 2305401 TI - A single-photon emission computed tomography study of hypoperfusion after subarachnoid hemorrhage. AB - We used single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime in 18 studies on 13 patients with subarachnoid hemorrhage to determine whether any changes in cerebral blood flow could be correlated with clinical or computed tomographic evidence of delayed ischemia. Among the seven patients without focal neurologic deficits, regional cerebral hypoperfusion was demonstrated in only one who died. Among the 10 patients with aneurysmal subarachnoid hemorrhage, one died before surgery, and six developed postoperative delayed ischemic deficits, of whom two died. Among the patients with angiographically documented aneurysms, regional hypoperfusion correlated with the presence and severity of delayed neurologic deficits, whereas correlative computed tomographic scans showed either early infarction or no relevant abnormality. This technique facilitates early diagnosis of cerebral tissue hypoperfusion due to vasospasm after subarachnoid hemorrhage. PMID- 2305402 TI - Geometric factors of the bifurcation in carotid atherogenesis. AB - In vitro studies have demonstrated that geometry of the carotid bifurcation predicts blood flow alterations associated with atherosclerotic plaque formation. We investigated intraindividual asymmetry of carotid atherosclerosis by measuring geometric aspects of the carotid bifurcation. We measured diameter stenosis, the internal carotid artery/common carotid artery area ratio, and the angle of the carotid bifurcation on 40 arteriograms. Stenosis asymmetry was significantly associated with area ratio asymmetry (r = 0.355, p less than 0.025); there was no such association between stenosis asymmetry and bifurcation angle asymmetry. Geometric factors of the carotid bifurcation, particularly the area ratio, may help explain intraindividual asymmetry in carotid atherosclerosis. PMID- 2305403 TI - Cerebral hemodynamic change in the child and the adult with moyamoya disease. AB - To clarify the differences in cerebral hemodynamics and metabolism between children and adults with bilateral moyamoya disease, we measured regional cerebral blood flow, regional oxygen extraction fraction, regional metabolic rate for oxygen, regional cerebral blood volume, and regional transit time using positron emission tomography in nine patients (five children and four adults) and compared the values with those in controls (four children with unilateral moyamoya disease and six normal adults). The major differences between pediatric and adult patients were in regional cerebral blood volume and regional oxygen extraction fraction. Regional cerebral blood volume was more markedly increased relative to the control value in the children than in the adults. Also, regional oxygen extraction fraction was greater than control in areas with low blood flow in the children but was never increased in the adults. However, in the adults, only regional transit time was significantly prolonged relative to the control values. The increased regional oxygen extraction fraction relative to the control value observed in children with moyamoya disease may explain why transient ischemic attacks are a common symptom in this group. PMID- 2305404 TI - Three-minute blood flow index for assessment of cerebrovascular reserve. AB - Regional cerebral blood flow studies with xenon-133 are useful in the functional assessment of cerebrovascular diseases. Conventional models for cerebral blood flow calculation employ 11 minutes of data collection. However, in many circumstances it is not possible to maintain steady-state physiologic conditions for 11 minutes. We compared a monocompartmental model that requires only 3 minutes of data collection with the bicompartmental model that requires 11 minutes of data collection. The correlation between the absolute values for global cerebral blood flow (initial slope index, intravenous method) in 72 anesthetized patients was r = 0.88; for 54 awake patients inhaling xenon-133, the correlation was r = 0.77. Cerebral blood flow was determined with intravenous xenon-133 at baseline and during a CO2 challenge in 50 patients during cerebrovascular surgery under general anesthesia. Reactivity to a 10-mm Hg rise in PaCO2 was calculated in absolute terms and as a percentage change from baseline using both the 3-minute and the 11-minute models. The correlation of CO2 reactivity calculated with the two models was r = 0.9 for the absolute values and r = 0.8 for the relative change. Cerebral blood flow calculated with the two models correlated well in both awake and anesthetized patients. In addition, there was a good correlation between CO2 reactivity calculated with the two models. In situations in which physiologic conditions cannot be held stable for 11 minutes, the 3-minute initial slope index may be used to quantitatively assess cerebrovascular reserve with a CO2 challenge. PMID- 2305405 TI - Cerebral blood flow and metabolism in normotensive and hypertensive patients with transient neurologic deficits. AB - We used positron emission tomography to examine retrospectively the effects of blood pressure on regional cerebral blood flow and oxygen metabolism in seven normotensive and eight hypertensive patients with a history of transient neurologic deficits. In the hypertensive patients, a decrease in regional cerebral blood flow was closely related to blood pressure; these changes were most pronounced in the supratentorial structures, especially the striatum and thalamus. In contrast, the regional cerebral metabolic rate for oxygen was less related to blood pressure. Consequently, the regional oxygen extraction fraction was increased in the hypertensive patients, while regional cerebral blood volume and the regional cerebral blood flow volume ratio were unchanged. Multivariate regression analysis confirmed that hypertension was an independent factor affecting regional cerebral blood flow. The analysis also disclosed that age, sex, hematocrit, smoking, and PaCO2 affected regional cerebral blood flow. These findings suggest that the hemodynamic reserve in hypertensive individuals is reduced, which may predispose them to cerebral ischemia and perhaps stroke, even during small decreases in cerebral perfusion pressure. PMID- 2305406 TI - Intracranial hemorrhage in patients with polycystic kidney disease. AB - To emphasize the important association of polycystic kidney disease and hypertensive cerebral hemorrhage, a registry of 900 consecutive cases of hemorrhagic stroke was reviewed. Eleven patients (1.2%) had intracranial hemorrhage (eight had hypertensive cerebral hemorrhage and the other three had aneurysmal subarachnoid hemorrhage) found to be associated with polycystic kidney disease. These 11 patients also accounted for 11% of the 98 cases of polycystic kidney disease during the 28-month study period. As verified by computed tomography, parenchymal hemorrhage occurred mainly in the putamen and the thalamus, the usual sites for hypertensive cerebral hemorrhage. One patient with cerebral hemorrhage was autopsied and one was studied angiographically, but in neither patient was an intracranial aneurysm identified. In the patients with polycystic kidney disease and intracranial hemorrhage, hypertension had been inadequately treated or even undetected; therefore, I emphasize early detection and more effective control of hypertension in patients with polycystic kidney disease for prophylaxis against hemorrhagic cerebrovascular events. PMID- 2305407 TI - Prospective study of anticardiolipin antibodies in stroke. AB - Over 2 years, 104 patients underwent clinical evaluation and laboratory screening for the presence of abnormal anticardiolipin antibodies to determine the profile of laboratory and clinical findings in patients with stroke and other neurologic disorders. Seven with incomplete or ambiguous data were excluded; of the remaining 97 patients, 31 were greater than or equal to 65 years old. Nine patients suffered systemic lupus erythematosus, 45 suffered brain ischemia, and 43 suffered other nonischemic neurologic disorders. Cardiac arrhythmia, myocardial infarction, and cardiac valvulopathy were grounds for exclusion. The presence of anticardiolipin antibodies was not influenced by age. In the 88 patients without lupus, anticardiolipin antibodies were significantly more common in the group suffering brain ischemia than in the group with nonischemic neurologic disorders (29% versus 5%, p less than 0.01, chi 2 test). These controlled data demonstrate an association between the presence of circulating anticardiolipin antibodies with stroke, but not with other neurologic conditions. PMID- 2305408 TI - Histologic assessment of neurons in rat models of cerebral ischemia. AB - We describe a method for typing neurons into four progressive stages of ischemic deterioration based on visual characterization of the nucleus in terms of its optical contrast, delineation along the nuclear-cytoplasmic interface, and its shape. Difficulty in assessing nuclear shape required the introduction of an angularity comparator chart to improve the investigator's accuracy. Three investigators typed neurons obtained from normal, ischemic, and ischemic reperfused rat brains. Accuracy and reproducibility of the investigators' typing decisions with and without the angularity comparator charts were evaluated. The accuracy of subjective shape assessment was compared with objective digitizer measurements of the same. The angularity comparator charts reduced subjective shape classification error by two thirds, and group error (overall performance expressed by the coefficient of variance) decreased from 15.9% to 4.7% for Type I (normal cells), from 33.9% to 17.3% for Type II (cells with angular nuclei), from 15.5% to 14.1% for Type III (cells with smeared nuclei), and from 3.2% to 5.5% for Type IV (dead cells). Thus, Type I and IV neurons can be assessed at a higher reproducibility than the intermediate Types II and III. Our typing method can also be used to evaluate the effect of treatment regimes on ischemic neuronal damage. PMID- 2305409 TI - Collateral development after carotid artery occlusion in Fischer 344 rats. AB - Mortality following permanent occlusion of both common carotid arteries decreases as the time between the first and second occlusions increases in Fischer 344 rats. Our goal was to examine the possibility that collaterals develop after unilateral carotid artery occlusion. During temporary occlusion of both carotid arteries in nine ketamine-anesthetized male rats, mean +/- SEM blood flow in both parietal cortices was 23 +/- 4% of the preocclusion (control) blood flow (120 +/- 7 ml/min/100 g) measured by laser Doppler flowmetry (p less than 0.05). After permanent occlusion of one carotid artery for either 1-2 days (n = 10) or 6 weeks (n = 7), mean +/- SEM blood flow was 16 +/- 2% and 30 +/- 3% of control, respectively, during a temporary test occlusion of the other carotid artery. During the test occlusion, blood flow in the cortex ipsilateral to the 6-week occlusion was 170% that in the contralateral cortex (which was similar to the blood flow immediately after temporary occlusion of both carotid arteries) and twice that after 1-2 days of occlusion. Mean luminal diameter of the basilar carotid anastomosis ipsilateral to the 6-week occlusion was 186% that of the contralateral anastomosis, which showed only minimal change, and 145% that after 1-2 days of occlusion. We conclude that during 6 weeks of permanent carotid artery occlusion the anastomosis enlarges and its blood flow or reserve increases. Thus, collaterals developed ipsilateral to, but not contralateral to, the 6-week carotid artery occlusion, which suggests the possibility of greater collateral protection on the permanently occluded side. PMID- 2305410 TI - Methionine sulfoximine reduces cortical infarct size in rats after middle cerebral artery occlusion. AB - The methionine analogue methionine sulfoximine was administered to 10 rats 24 hours before occlusion of the proximal left middle cerebral artery. Three days later the rats were decapitated and the brain infarct volumes were compared with those in 10 control rats that received saline before middle cerebral artery occlusion. The mean volume of the infarct in the cerebral cortex was reduced by 33% in the group treated with methionine sulfoximine (p less than 0.01). This protective effect may be mediated by a presynaptic mechanism; methionine sulfoximine profoundly inhibits brain glutamine synthetase, thereby interrupting the astrocyte-neuron glutamate shuttle and impairing neuronal glutamate release. Methionine sulfoximine also increases brain glycogen stores, and this increased energy reserve may benefit penumbral tissue during the peri-infarct period. Further study of the mechanisms by which methionine sulfoximine decreases infarct volume could lead to new therapeutic approaches for stroke. PMID- 2305411 TI - Variable angiographic findings in patients with stroke and neurosyphilis. AB - We describe four patients with cerebral infarction and active neurosyphilis who had variable angiographic findings. Patients 1 and 2 had evidence of arteritis and an atheromatous ulcerated stenosis of the extracranial carotid artery, respectively. The third and fourth patients had symptoms of lacunar infarction, but cerebral angiography was normal in patient 3, whereas patient 4 had evidence of concomitant atheromatous and arteritic lesions. Neither age nor presence of cerebrovascular risk factors was of aid in predicting angiographic features. The concomitance of cerebral infarction and active neurosyphilis does not imply a cause-and-effect relation, since atherosclerotic lesions may coexist with arteritis or may even represent the only angiographic feature. Our findings underscore the importance of angiography to confirm the diagnosis in cases of suspected syphilitic arteritis. PMID- 2305412 TI - Ataxic hemiparesis following thalamic infarction. AB - We describe a 73-year-old man with ataxic hemiparesis following infarction of the ventrolateral nucleus of the thalamus demonstrated by computed tomography and magnetic resonance imaging. Cerebellar ataxia was most likely due to interruption of the dentatorubrothalamocortical fibers at the level of the injured ventrolateral nucleus. Hemiparesis was probably caused by local edema compressing the corticospinal tract in the adjacent posterior limb of the internal capsule. We believe this to be the first reported case of classic ataxic hemiparesis following thalamic infarction. PMID- 2305413 TI - Effect of hyperglycemia on infarct size after cerebrovascular occlusion in cats. PMID- 2305414 TI - Impairment of theophylline clearance by a hypocaloric low-protein diet in chronic obstructive pulmonary disease. AB - The effect of a hypocaloric, low protein diet on theophylline kinetics was studied in a 70-year-old man with chronic obstructive pulmonary disease who lost 6.2 kg of weight. Total systemic clearance, unbound clearance, and intrinsic hepatic clearance fell dramatically. Theophylline elimination half-life rose from 8.4 to 17.1 h. Therefore, a diet deficient in both calories and protein can significantly impair theophylline clearance and prolong theophylline elimination half-life. PMID- 2305415 TI - Bayesian estimation of cyclosporine clearance in bone marrow graft. AB - The dosage regimen of cyclosporine (CsA) can be individualized in patients by means of a test dose (TD) method in the few days before bone marrow graft. To simplify the test dosing protocol, we used a Bayesian estimation (BE) of CsA clearance requiring population data and partial kinetic information for a given patient. In the first part, 42 patients, aged 11-47 years, were given a 2-h infusion of CsA (4 mg.kg-1). CsA concentrations were determined in several blood samples. The obtained concentration-time curves were fitted according to a three compartment model. Maximum likelihood estimation (MLE) allowed CsA determination of pharmacokinetic parameters. Early population parameters of CsA were determined using 22 TD by a two-stage method. In the remaining 20 patients, individual pharmacokinetic parameters were also computed by BE procedure, taking into account the above determined population parameters and CsA concentration determinations from three blood samples drawn at 5 and 30 min and 3 h after the end of TD infusion. In the second part, 16 patients were used to evaluate performance of BE in directly predicting target concentration values. Finally, early population characteristics were updated on the basis of 42 patients. Statistical comparisons between MLE and BE estimates of CsA clearance and between concentrations predicted after BE and those experimentally obtained showed that three blood CsA determinations allowed accurate clearance estimation and target concentration predictions. The method presented here can be used to calculate an individual CsA dosage regimen in real time, thus improving patient comfort.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305416 TI - Onset and development of cyclosporin A effects on lymphocytes of cardiac patients before heart transplantation. AB - The effects of cyclosporin A (CSA) in low dosage (4 mg/kg/24 h i.v.) were studied in 17 patients awaiting heart transplantation. The lymphocyte subsets were typed, enumerated, and their proliferation measured before CSA perfusion, after infusion (over 24 h), and then again after two further 24 h intervals (T0 h, T24 h, T48 h, and T72 h). No significant change was found in T or B enumerations although lymphocyte function was markedly modified. For all 17 patients, there was a significant decrease in lymphocyte proliferation that was, however, re established after 72 h for 14 of the patients, but not for the remaining 3. Inhibition of the proliferative response was found to occur rapidly, to be potent although rapidly reversible in most cases, while yet subject to wide interindividual variability. These four features suggest that (a) CSA in fixed doses may later the balance between helper and suppressor cells in varying degrees according to the patient, and that (b) CSA given immediately or shortly after heart transplantation could be beneficial. PMID- 2305417 TI - Antiarrhythmic activity and unbound concentrations of disopyramide enantiomers in patients. AB - Six patients with reproducible inducible atrial flutter randomly received, in double-blinded fashion, 77 mg of S(+)-disopyramide and R(-)-disopyramide over 20 min by intravenous infusion on two occasions separated by at least 24 h. The S(+) enantiomer prevented the inducibility of atrial flutter in five of the six patients; atrial flutter was inducible following R(-) enantiomer administration in all six patients (p less than 0.05). The mean (+/- SD) antiarrhythmic unbound serum concentration range of S(+)-disopyramide was 0.55 +/- 0.31-0.90 +/- 0.81 mg/L. The binding of disopyramide was stereoselective: the mean unbound fractions of S(+)- and R(-)-disopyramide were 0.207 +/- 0.119 and 0.338 +/- 0.214 (p less than 0.05). Binding of the individual enantiomers in some patients was markedly concentration dependent. The data suggest that the antiarrhythmic activity associated with racemic disopyramide resides in the S(+) enantiomer. PMID- 2305418 TI - Pharmacokinetics of intravenous vancomycin in patients with end-stage renal failure. AB - The pharmacokinetics of a 500-mg dose of i.v. vancomycin were studied in six Chinese patients with end-stage renal failure. Serum vancomycin concentrations were determined by high-performance liquid chromatography. Observed peak and trough (at 168 h postinfusion) concentrations were in the range of 14.2-35.0 micrograms/ml and 2.8-5.5 micrograms/ml, respectively. The data were analyzed using the PCNONLIN. In all six patients, the data could be fitted well by both the biexponential and triexponential models, but in three patients the latter model provided a better fit. Two-compartment pharmacokinetic parameters obtained from the six patients were t 1/2 alpha 1.13 +/- 0.25 h (mean +/- SEM), t 1/2 beta 121.3 +/- 8.2 h, Vc 0.45 +/- 0.09 L/kg, Vss 1.00 +/- 0.12 L/kg, ClT 5.90 +/- 0.69 ml/kg/h, and the calculated Cmax 25.0 +/- 6.1 micrograms/ml. The mean vancomycin serum protein binding was 18.5 +/- 12.0% as compared with a mean of 46.0% in pooled serum from normal controls. Hemodialysis had no significant effect on vancomycin protein binding or clearance. On the basis of our kinetic study, 500 mg of vancomycin given every seven days is probably adequate treatment for methicillin resistant Staphylococcus aureus infection in end-stage renal failure patients, but further clinical studies are necessary to confirm this. PMID- 2305419 TI - Validity of a two-point acetaminophen pharmacokinetic study. AB - The pharmacokinetics of a single 650-mg intravenous dose of acetaminophen were determined in 82 volunteers using multiple (13 or more) plasma acetaminophen concentrations measured by high pressure liquid chromatography during 24 h after dosage. Kinetic values from the complete study were compared with kinetic estimates based on only two data points: (a) the 2- and 6-h points only; and (b) the 3 and 6-h points only. For elimination half-life, values from the complete study (mean 2.42 h) were highly correlated (r = 0.87 and 0.84) with methods a and b (means 2.41 and 2.43 h), with regression slopes of 1.00 and 0.99, respectively. For clearance, the complete study values (mean 312 ml/min) were highly correlated (r = 0.97 and 0.97) with method a and b values, but both two-point methods significantly overestimated clearance (means 350 and 355 ml/min) by an average of 13 and 14%, respectively. Results for volume of distribution were similar to those for clearance. Although acetaminophen elimination half-life can be estimated with reasonable precision using a two-point blood-sampling procedure, clearance and volume of distribution values using the two-point method overestimate the actual values. PMID- 2305421 TI - An evaluation of Bayesian microcomputer predictions of theophylline concentrations in newborn infants. AB - Determination of appropriate theophylline maintenance doses in preterm infants is confounded by interpatient variability. This study evaluated the performance of an IBM PC computer program applying Bayesian regression before and during steady state in 37 preterm infants. Prior population estimates of clearance and distribution volume in preterm infants and Bayesian estimates of clearance and distribution volume based on one to three theophylline plasma concentrations were used to predict subsequent concentrations (drawn 1-17 days later). We assessed the accuracy and precision of the predictive performance of the Bayesian program with the mean prediction error and the mean absolute prediction error. The absolute prediction error (mean absolute error +/- SEM) significantly decreased with increasing feedback concentrations from 3.54 +/- 0.45 micrograms/ml (population estimates) to 2.74 +/- 0.42 (one feedback) and 2.02 +/- 0.35 micrograms/ml (two feedback concentrations). Mean prediction errors (+/- SEM) based on one to three feedbacks (-1.5 +/- 0.40 micrograms/ml) were significant improvements over population predictions (-2.63 +/- 0.72 micrograms/ml, p less than 0.05), although a small but significant average overprediction remained. Absolute prediction error was correlated with postconceptional and postnatal age when zero or one but not two feedback concentrations were available. Computer program predictions based on one measured feedback concentration were more accurate and precise than population-based predictions. Refinement of population parameters or two feedback concentrations further improved performance. PMID- 2305420 TI - Protein binding of antiepileptic drugs during pregnancy, labor, and puerperium. AB - Twenty-four epileptic women were followed-up during late pregnancy, labor, and early puerperium in order to detect possible alterations in serum protein binding of antiepileptic drugs (AEDs). The total and free concentrations of carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) in maternal serum were measured. In addition, the concentrations of albumin, alpha 1-acid glycoprotein (AGP), and free fatty acids (FFA) were also measured. Total AED concentrations during labor were influenced by changes in drug dosages; total PHT increased during the first puerperal weeks. During labor the free fraction of CBZ remained stable, whereas PHT and particularly VPA free fractions increased. This phenomenon was parallel to the increase in FFA concentration; FFA concentrations decreased again during the first days postpartum. Albumin and AGP concentrations were low during pregnancy and labor, and increased after delivery. The total umbilical CBZ and PHT concentrations were not significantly different from maternal concentrations. The total VPA concentration in umbilical serum was significantly higher than that in maternal serum. The free fraction of CBZ was higher and that of PHT and VPA lower in umbilical than in maternal serum at delivery. Umbilical cord serum had a higher albumin but a lower AGP and FFA concentration than maternal serum. The changes in PHT and particularly VPA free fraction associated with changes in FFA concentration should be considered when assessing the total concentration of these drugs in maternal and umbilical serum. PMID- 2305422 TI - Theophylline pharmacokinetics in black Zimbabwean males. AB - Theophylline pharmacokinetics were studied in 16 black Zimbabwean volunteers aged 20-41 years. Following a single intravenous dose of 5 mg/kg, four serum levels were collected over 24 h. Data were analyzed using a one-compartment open model. The correlation coefficient was 0.995 +/- 0.004. The mean extrapolated peak level was 8.5 +/- 0.9 mg/L. The mean half-life and volume of distribution were 10.1 +/- 3.1 h and 0.55 +/- 0.7 L/kg, respectively. The mean clearance was 0.62 +/- 0.17 ml/kg/min. The mean weight was 7 kg less than the calculated ideal body weight. These data suggest a larger volume of distribution and longer half-life than in other reported populations. The clearance is on the low end of previously reported values. We postulate that the primary cause of the large volume is the decreased body fat and consequent increase in body water per kilogram. The slightly decreased clearance may have been partially due to the high carbohydrate, low protein diet of our subjects. The long half-life is simply a reflection of a large volume and a moderately low clearance. We suggest that standard per kilogram maintenance doses can be employed in this population. A larger loading dose of 8 mg/kg aminophylline is recommended. Finally, the lack of sustained release theophylline in Zimbabwe may not be a problem, given the longer half lives observed in this study. PMID- 2305423 TI - Single oral dose pharmacokinetics of erythromycin and roxithromycin and the effects of chronic dosing. AB - Roxithromycin is a semisynthetic macrolide antibiotic having similar in vitro antibacterial profile and potency to erythromycin but possibly greater in vivo potency. The single and multiple oral dose pharmacokinetics of roxithromycin and erythromycin were studied in 12 healthy volunteers. Plasma concentrations of the two compounds were measured by a sensitive and specific high-performance liquid chromatographic method using electrochemical detection. After single doses, roxithromycin 150 mg gave a Cmax 3.3-fold higher and an area under the curve (AUC) 16.2-fold higher than erythromycin 250 mg. The half-life for roxithromycin was 12.42 +/- 3.94 h compared with 1.53 +/- 0.42 h for erythromycin. On multiple dosing, the AUC over a dosing interval for erythromycin (250 mg, six hourly doses) was increased 2.3-fold compared with the single dose, whereas that for roxithromycin (150 mg, 12 hourly) was decreased by 25.4%. Because of these opposing changes during chronic dosing, the average plasma roxithromycin concentration over the dosing interval was 2.6-fold higher than that for erythromycin, which was a smaller excess than would have been predicted from the single dose data. The results suggest that roxithromycin exerts less inducing and inhibiting effects on human cytochrome P450 than erythromycin. Roxithromycin has a favorable pharmacokinetic profile suitable for twice daily dosing and may have a lower potential than erythromycin for cytochrome P450-mediated drug interactions. PMID- 2305424 TI - Therapeutic drug monitoring in a community hospital. AB - This study describes an aminoglycoside dosing service in a community hospital. Between 95 and 98% of all aminoglycoside doses are calculated by staff pharmacists using traditional pharmacokinetic equations. All patients dosed by the pharmacy are then monitored by clinical pharmacists who make necessary dosage modifications following serum peak and trough levels. After the first year of this service, it was determined that a slight change in the volume of distribution equation would allow the pharmacy to calculate maintenance doses that would more accurately result in estimated serum peak and trough levels. Physicians are pleased with this service and professional job satisfaction is experienced by the pharmacists. Therapeutic drug monitoring is an important component of patient care and can be implemented in community hospitals. Other pharmacy departments are encouraged to establish similar services. PMID- 2305425 TI - Influence of spironolactone and its metabolite canrenone on serum digoxin assays. AB - Although current immunoassay kits for digoxin supposedly have antibodies of high specificity, serum digoxin levels in patients taking spironolactone suggest that spironolactone interferes with the determination. In vitro determinations of digoxin performed on blank serum spiked with spironolactone and its metabolite canrenone showed that contrary to the belief gained from reading the manuals of some diagnostic immunoassay kits, spironolactone significantly influences digoxin determinations. PMID- 2305426 TI - Stability of phenytoin in blood collected in vacuum blood collection tubes. AB - The stability of phenytoin in blood collected in plain and serum separator tubes (SSTs) was investigated under simulated storage and transport conditions. The drug was generally more stable in plain collection tubes than in SSTs. No degradation occurred in plain red-top tubes or in refrigerated SSTs, but clinically significant degradation was present in SSTs stored at room temperature (25 degrees C) and at elevated temperature (32 degrees C) 24 h after collection. The mean loss was 17.9% at 25 degrees C and 25.9% at 32 degrees C. It is recommended that if blood is to be transported or stored in SSTs, the samples be refrigerated unless assay can be performed within 8 h. PMID- 2305427 TI - Simultaneous assay of felbamate plus carbamazepine, phenytoin, and their metabolites by liquid chromatography with mobile phase optimization. AB - Felbamate is an investigational antiepileptic drug (AED) in clinical trials. A high-performance liquid chromatographic method for the simultaneous analysis of felbamate, phenytoin (PHT), 5-(p-hydroxyphenyl)-5-phenylhydantoin, carbamazepine (CBZ), carbamazepine-10,11-epoxide, and carbamazepine-10,11-diol in serum was developed by a mobile phase optimization technique. Capacity factors for the compounds of interest and 12 other AEDs and metabolites were determined with mixtures of methanol, acetonitrile, or tetrahydrofuran and a 0.01 M ammonium phosphate buffer, pH 6.5, on a reversed-phase C8 column. An optimized mobile phase composition was determined that could separate the compounds of interest and three internal standards in less than 15 min. Serum was extracted with CH2Cl2/ethyl acetate (2:1) after addition of three internal standards. The method was validated for within-day and between-day precision and accuracy for the six compounds. Coefficients of variation were generally less than 10% at all concentrations and less than 5% in the typical therapeutic range for each compound. The lower limit of detection was estimated at 0.2 micrograms/ml for CBZ and its metabolites and 0.5 micrograms/ml for felbamate and PHT. For felbamate, the lowest point on the standard curve was 1.88 micrograms/ml with a between-day variability of 10.3%. The assay was used to determine the serum concentrations of PHT and CBZ and its metabolites in a subject before, during, and after felbamate therapy. PMID- 2305429 TI - The malpractice nightmare. Round table discussion. PMID- 2305428 TI - Simultaneous determination of dextromethorphan and three metabolites in plasma and urine using high-performance liquid chromatography with application to their disposition in man. AB - A simple, sensitive, and reproducible high-performance liquid chromatrography assay is described for the simultaneous determination of dextromethophan, dextrorphan, 3-hydroxymorphinan, and 3-methoxymorphinan in plasma and urine. A conventional solvent-solvent extraction procedure was used for the isolation of the analytes from plasma and urine samples. The compounds were separated on a cyano column (150 x 4.6 mm, 5-micron particle size) using a mobile phase of acetonitrile/triethylamine/distilled water (17:0.06:82.94, vol/vol), pH 3.0, and then were measured by fluorescence detection. Calibration curves in the range 2 200 ng/ml for plasma and 0.05-10 micrograms/ml for urine were linear and passed through the origin. The precision and accuracy were greater than 90% and the lowest detectable concentrations were 0.5 ng/ml for 3-hydroxymorphinan and 3 methoxymorphinan and 1 ng/ml for dextromethorphan and dextrophan in plasma. The utility of this method is demonstrated in a preliminary study of dextromethorphan metabolism and pharmacokinetics in man. PMID- 2305431 TI - OR nursing looks to the future. PMID- 2305430 TI - Motivating the staff toward job enrichment. PMID- 2305432 TI - Nursing diagnosis in the O.R. Perioperative application. PMID- 2305433 TI - Using confrontation in the OR. AB - Whereas some managers choose to avoid confrontation because it is likely to sound punitive or provoke self-defensive or aggressive responses, others use it extensively, believing that confrontation holds people accountable for their behaviors. The final decision on how much, when, and with whom to use confrontation must be based on a deliberate evaluation of the situation and the best judgment of the manager. PMID- 2305434 TI - Marketing ambulatory surgery centers. PMID- 2305435 TI - Surgical arthroscopy for anterior cruciate ligament reconstruction. PMID- 2305436 TI - Cryosurgery: liver metastases frozen in place. PMID- 2305437 TI - Percutaneous umbilical blood sampling and umbilical vein transfusions. Rapid serologic differentiation of fetal blood from maternal blood. AB - Percutaneous umbilical blood samples (PUBS), obtained under ultrasound guidance, are used for prenatal diagnosis and management of hemolytic disease of the newborn (HDN) and other fetal disorders. Rapid testing at the time of sampling is vital to distinguish fetal from maternal blood. Blood typing was performed by slide technique in the treatment room during 38 procedures on 25 patients. Anti-I was used to test 50 presumed PUBS; venous I-positive maternal blood was tested in parallel. Because anti-I cannot detect fetal blood after umbilical vein transfusion (UVT) of I-positive donor blood, ABO and Rh blood typing reagents were used to test 29 samples when maternal and fetal or donor blood groups differed. Monoclonal reagents were used for optimal detection of weak AB antigens in fetal blood. Avid, chemically modified anti-D was used for Rh typing. Blood typing showed 27 (34%) of 79 samples to be maternal blood. Fetal blood was obtained in 8 of 10 cases investigated for fetal disorder and in 16 cases of potential HDN (anti-D, 5; -CD, 5; -cE, 2; -K, 2; -c; -E). The absence of HDN (antigen-negative fetus) was determined in 4 cases. UVT afforded live birth of 9 of 10 infants with HDN and was not indicated in two cases. PMID- 2305438 TI - The gel test: a new way to detect red cell antigen-antibody reactions. AB - A new process for the detection of red cell (RBC) antigen antibody reactions is described. It is applicable to most of the tests performed in blood group serology. The procedures are standardized and easy, and they provide clear and stable reactions that improve the interpretation of results. The process uses special microtubes filled with a mixture of gel, buffer, and reagent. Depending on the test to be carried out, the test uses a neutral gel containing no reagents (reagents are added to top of gel) or a specific gel containing reagents (e.g., antiglobulin serum or anti-A, -B, -D, etc.). A suspension of RBCs (for typing or the direct antiglobulin test) or a mixture of RBCs and serum (for reverse ABO typing or antibody characterization) is centrifuged through the gel under precise conditions. In negative reactions, the RBCs pass through the gel and pellet in the bottom of the tube, whereas, in positive reactions, they are trapped in the gel and the reaction may be read for hours afterwards. The test is easy to perform, sensitive, and reproducible. The antiglobulin tests can be performed without washing of the RBCs. There should be a reduction of risk from biohazardous materials. PMID- 2305439 TI - Solid-phase antiglobulin test for screening and identification of red cell antibodies. AB - A newly developed automatically readable solid-phase antiglobulin test is described. The solid-phase test in comparison with conventional antiglobulin techniques for screening and identification of red cell antibodies showed agreement in 2346 (98.7%) of samples tested. The increased sensitivity of the solid-phase antiglobulin test is demonstrated by examination of serial twofold dilutions of antibodies. PMID- 2305440 TI - A new radioimmunoassay for the detection of small amounts of white cells and platelets in red cell concentrates: implications for blood transfusion. AB - In the procedure for quality control of red cell concentrates, made white cell (WBC)-poor by filtration, the particle-counting technique was found to be insufficiently sensitive in detecting the remaining WBCs and platelets. Therefore, direct radioimmunoassays were developed using murine monoclonal antibodies specific for platelets, granulocytes, and T lymphocytes. The sensitivity for platelets was 40 x 10(3) per mL, that for granulocytes was 10 x 10(3) per mL (starting from 0.2 mL of red cell filtrate), and that for T lymphocytes was 0.006 x 10(6) per mL (starting from 5 mL) and 0.0015 x 10(6) per mL (starting from 50 mL). These direct assays were used in experiments on filtration with three types of filters: the Cellselect B-1005, B-1014 and the B 1013 (bedside filter). After filtration of 1 unit of blood cell suspension through the B-1005, the number of remaining platelets was found to vary between less than or equal to 0.04 x 10(6) and greater than 15 x 10(6) per mL (n = 16); after filtration through the B-1013 filter, the remaining platelets were greater than 0.04 x 10(6) per mL. Upon filtration of a second unit of blood cell suspension through the B-1013 filter, the number of remaining platelets varied between less than or equal to 0.04 x 10(6) and 5 x 10(6). In both filter types, the number of remaining granulocytes was always less than 0.01 x 10(6) per mL. A study of T-lymphocyte contamination revealed that, upon filtration of 1 unit of blood through the B-1005, T-lymphocyte numbers were less than or equal to 0.0015 x 10(6) to 0.15 x 10(6) per mL (starting from 5 and 50 mL); upon filtration through the B-1013 filter, the number of remaining T lymphocytes varied between less than or equal to 0.006 x 10(6) and 0.2 x 10(6) per mL (starting from 5 mL). After filtration of a second unit of blood cell suspension through the B-1013 filter, the number of remaining T lymphocytes ranged from less than or equal to 0.006 x 10(6) to 0.1 to 0.5 x 10(6) per mL (starting from 5 mL). The direct radioimmunoassay is an improvement over the present electronic particle-counting techniques with regard to both sensitivity and specificity and may therefore be useful in quality control procedures in blood transfusion as well as in the development of new filters. PMID- 2305441 TI - Red cell transfusion therapy for anemia in patients with AIDS and ARC: incidence, associated factors, and outcome. AB - The records of the San Francisco General Hospital (SFGH) Blood Bank were reviewed, and 263 likely AIDS and AIDS-related complex (ARC) patients were identified, who received 1545 units of packed red cells (PBRCs) between July 1, 1987, and June 30, 1988. A probability sample of 80 of these patients was selected randomly for detailed chart review. Of this sample, 78 (98%) were confirmed to have AIDS (86%) or ARC (14%). On the basis of the yearly census of the SFGH AIDS clinic, a transfusion incidence of 0.89 PRBC units per patient per year for patients with AIDS and 0.27 PRBC units per patient per year for those with ARC was estimated. Whereas 26 percent of the 177 transfusions studied in detail involved more than one associated (possibly causative) factor, antimicrobial drug therapy, zidovudine therapy, and disseminated Mycobacterium avium complex (MAC) infection were the sole associated factors in 20, 14, and 12 percent of the transfusions, respectively. To assess the role of MAC, the 263 transfused patients were compared with the 574 patients whose blood was submitted to the SFGH Mycobacteriology Laboratory during the same period. Patients whose blood yielded MAC had a relative risk of 5.2 for transfusion-requiring anemia. In 80 percent of cases, the patient returned home after transfusion. Most PRBC transfusions administered to AIDS or ARC patients were optimal therapy. PMID- 2305442 TI - The first-year costs of establishing an unrelated bone marrow donor registry. AB - The cost of therapies like bone marrow transplantation has been an important consideration for several decades. Bone marrow transplantation is becoming increasingly accepted as an effective treatment for hematologic disorders, including acute nonlymphocytic leukemia. To find suitable donors, bone marrow donor registries are being developed. The first-year costs of establishing an unrelated bone marrow donor registry are reported here. First-year costs are largely due to personnel costs and HLA typing charges. The cost per registrant decreases over time, but further decreases due to economies of scale are limited by the continued fixed requirement for HLA typing. Data are presented by separating costs into six unique categories, thereby allowing other blood centers to estimate start-up costs based on our experience. PMID- 2305443 TI - Invalidation of antiglobulin tests by a high thermal amplitude cryoglobulin. AB - A multiply transfused patient was referred for evaluation of a transfusion reaction. The direct and indirect antiglobulin tests (DAT, IAT) for alloantibody were negative. However, IgG-coated control cells failed to agglutinate in the negative reactions, casting doubt on their validity. At 4 degrees C, the patient's serum exhibited a large cryoprecipitate (2.9 mg/mL), made up predominantly of an IgG kappa paraprotein and having trace amounts of IgM and C3. Clear serum separated at 37 degrees C became cloudy within 10 minutes at room temperature (RT); within 4 hours, approximately 60 percent of the total precipitable cryoprotein had precipitated. Red cells (RBCs) incubated in fresh serum that had cooled to RT or RBCs obtained from RT or refrigerated samples contained cryoprecipitate that sedimented with the RBCs during washing with RT saline. On resuspension, enough IgG cryoglobulin redissolved to neutralize completely the commercial anti-IgG reagents. If the patient's samples were maintained at 37 degrees C, cryoprecipitate did not form, and RBCs washed four times at 37 degrees C gave valid DAT and IAT reactions. The removal of all cryoprecipitate from the patient's serum by centrifugation after overnight incubation at 4 degrees C also made possible valid antibody screening and compatibility tests. PMID- 2305445 TI - Controversies in transfusion medicine. Autologous blood donation in pregnancy: con. PMID- 2305444 TI - Controversies in transfusion medicine. The safety and utility of autologous donations by pregnant patients: pro. PMID- 2305446 TI - Effect of blood transfusions on experimental pulmonary metastases in mice. AB - We examined the effect of allogeneic blood transfusions (BT) on pulmonary metastases in a mouse model. Recipient (C57B1/6J) mice were transfused with either saline, syngeneic blood or allogeneic (Balb/c) blood on two occasions, days 0 and 3. One week after the last transfusion, recipient mice were injected intravenously with varying numbers of methylcholanthrene-induced fibrosarcoma cells. Twenty days later the number of pleural nodules was counted as an index of pulmonary metastasis. The data demonstrate that the inoculation of 2.5 x 10(5) or 1 x 10(5) tumor cells resulted in significantly higher numbers of pulmonary metastases in mice that received allogeneic BT than the mice that received syngeneic blood or saline. In contrast, allogeneic BT caused significant inhibition of pulmonary metastases in mice that received 3.5 x 10(5) tumor cells. The data suggest that the immunomodulatory (stimulatory or inhibitory) effect of BT is dependent on the numbers of tumor cells inoculated. It is likely that the conflicting reports in the literature on the effects of BT on tumor growth may be due to inoculation of different numbers of tumor cells. These results have an important bearing in understanding the effect of allogeneic BT on tumor growth both in experimental animals and in cancer patients. PMID- 2305447 TI - Can the efficacy of white cell depletion as a means to eliminate transfusion transmitted AIDS ever be proved in man? PMID- 2305448 TI - Absence of graft-versus-leukemia effect of standard hemotherapy in patients with acute myeloblastic leukemia. PMID- 2305449 TI - Inactivation of HIV-2 by solvent/detergent treatment. PMID- 2305450 TI - The National Heart, Lung, and Blood Institute and transfusion medicine. PMID- 2305451 TI - A look to the future in transplantation. PMID- 2305452 TI - Elimination of acute GVHD and prolongation of rat pancreas allograft survival with DST cyclosporine, and spleen transplantation. AB - Allogeneic spleen transplantation has been shown to have a tolerizing effect on pancreas allograft survival in rats. In this study we examined the effect of blood transfusions and cyclosporine administration on both rat pancreas allograft survival and acute graft-versus-host disease in BN recipients of Lewis pancreas spleen allografts. We found that in this strain combination significant pancreas allograft prolongation occurred when the spleen was included en bloc with the pancreas graft. However, 50% of these recipients developed GVHD and died. A single donor-specific transfusion delivered to BN recipients of Lewis pancreas and pancreas-spleen allografts did not extend graft survival, but precluded the development of GVHD. A short, 6-day, and long, 26-day, course of CsA to recipients of pancreas and pancreas-spleen allografts extended graft and animal survival times, although not indefinitely. All pancreas-spleen recipients of both CsA protocols died following acute GVHD. Combined DST and CsA (short and long course) administration in pancreas-only allograft recipients was deleterious to graft survival, compared with CsA administration alone. However, in pancreas spleen recipients, combined DST and CsA had an additive effect. Moreover, in DST and long-course CsA-treated pancreas-spleen recipients, indefinite graft survival occurred with no signs of acute GVHD. The beneficial effect of the spleen allograft on pancreas graft survival was not dependent upon GVHD, since splenic induced prolongation of pancreas graft survival was observed in the F1-donor to parent-recipient combination. PMID- 2305454 TI - Optimal cardioplegia and 24-hour heart storage with simplified UW solution containing polyethylene glycol. AB - Recent work has shown that UW may be better than standard cardioplegic solutions for short-term heart preservation. In this study we have used a rabbit heart model to evaluate a simplified UW solution in which penicillin, dexamethasone, insulin, allopurinol, and adenosine were omitted and 5% polyethylene glycol (PEG20M) was substituted for hydroxyethyl starch. The test systems consisted of 4 hr cardioplegic storage at 15 degrees C with repeated flushing every 30 min for 2 hr and 24-hr hypoxic low-flow microperfusion (3 ml/g/24 hr) at 0 degrees C. Control groups were arrested with a 15-25 ml flush in iced saline and immediately tested. Cardiac output (CO)* after preservation was measured in a working heart model using an acellular perfusate at 37 degrees C at an aortic pressure of 100 cm H2O. The CO (ml/g heart wt/min) were as follows--Controls: St. Thomas II 20.5 +/- 8.3 (5), UW 34.7 +/- 11.7 (16), PEG20M 41.8 +/- 4.4 (14); 4-hr cardioplegia: St. Thomas II 17.4 +/- 0.9 (4), Bretschneider HTK 14.9 +/- 7.0 (4), UW 25.2 +/- 11.5 (9), PEG20M 41.1 +/- 7.8 (8); 24-hr microperfusion: UW 25.4 +/- 11.1 (18), PEG20M 37.1 +/- 8.2 (18). Following cardioplegic or microperfusion preservation, PEG20M hearts functioned at control levels (P greater than 0.05) and were significantly superior to all other solutions, with approximately double the CO (P less than 0.05, all other groups). We conclude that for heart preservation, 5 components can be eliminated from UW and substitution of PEG20M for HES appears to have improved its performance. PMID- 2305453 TI - Seventy-two-hour preservation of the canine liver by machine perfusion. AB - The UW solution effectively preserves the dog liver for up to 48 hr by simple cold storage. This solution contains lactobionate as the primary impermeant. Another solution developed for machine perfusion of the kidney is similar to the UW solution but contains gluconate in place of lactobionate. In this study the UW gluconate solution was used for the continuous hypothermic machine perfusion of dog livers for 72 hr. Dog livers were continuously perfused at 5 degrees C through the portal vein at a pressure of 16-18 mm Hg and transplanted. Seven of 8 dogs survived for 7 or more days following orthotopic transplantation. The livers functioned as well as those preserved for 48 hr by cold storage in the UW solution as indicated by various liver-function tests. Successful machine perfusion was only achieved when the perfusate contained a high concentration of potassium (125 mM) but not with a high concentration of sodium (125 mM). This study demonstrates the feasibility of machine-perfusion preservation of the liver that yields longer preservation of equal quality compared to simple cold storage. For the development of truly long-term preservation (5 or more days) and better quality short-term preservation, machine perfusion may be the method of choice. PMID- 2305455 TI - The production of tumor necrosis factor alpha and the development of a pulmonary capillary injury following hepatic ischemia/reperfusion. AB - The large mass of fixed macrophages resident in the liver make it a potentially rich source of cytokines. We have previously demonstrated that an isolated and severe ischemia/reperfusion injury to the liver results in cytokine release, specifically tumor necrosis factor alpha, and that TNF is then involved in the development of pulmonary pathology. This study was designed to determine the kinetics of TNF release following varying periods of hepatic ischemia and to further investigate the acute lung injury that follows. Suprahepatic blood samples were obtained at serial time points following a 45-, 60-, 75-, or 90-min ischemic insult to a segment of the rat liver with subsequent reperfusion. Using a bioassay based on the WEHI 164 cell line, plasma TNF levels were measured in all experimental animals; sham-operated control animals had undetectable levels. Changes in pulmonary capillary permeability were then measured using a standard 125I-labeled albumin washout technique following a 90-min ischemic insult with subsequent reperfusion. A significant increase in the mean permeability index was observed 9 to 12 hr following hepatic reperfusion (.601 +/- 102 as compared with .114 +/- .085 in sham-operated controls, P less than 0.005). Animals treated with anti-TNF antiserum prior to the induction of hepatic ischemia had a significantly reduced pulmonary capillary leak compared to animals pretreated with rabbit serum without TNF-blocking properties (.184 +/- .029 versus .694 +/- 052 for the control serum, P less than 0.005). TNF release follows both moderate and severe ischemic injury to the liver and the results reported here implicate TNF as an important mediator of increased pulmonary capillary permeability. These experiments confirm previous histologic studies that demonstrated pulmonary edema and intra-alveolar hemorrhage following hepatic ischemia/reperfusion, with subsequent blockade of the histologic injury by pretreatment with anti-TNF antiserum. PMID- 2305456 TI - Immune function in transplanted small intestine. Total secretory IgA production and response against cholera toxin. AB - Secretory IgA is the dominant immunoglobulin produced in the small intestine and one important component of the local defense against dietary and infectious agents present in the gut lumen. The effect of small intestine transplantation on total production of sIgA and on the response to a newly presented antigen, cholera toxin, was determined in a rat segmental heterotopic intestinal transplant model. Lewis x Brown Norway F1 (LBNF1) allografts in Lewis hosts made normal amounts of sIgA, when compared with LBNF1 Thiry-Vella loops or LBNF1 isografts. In contrast, the allografts failed to make a significant specific sIgA response when immunized with cholera toxin at days 0 and 7 following transplantation. This failure was not the result of surgical manipulation, as isografts made normal amounts of specific sIgA directed against cholera toxin. Cyclosporine immunosuppression delayed, but did not prevent, the secretion of specific antibody in isografts. This failure to respond to a new antigen may have important implications for the safety of small bowel transplantation. PMID- 2305457 TI - Comparison of UW solution and Euro-Collins solutions for cold preservation of human liver grafts. AB - University of Wisconsin solution, a new organ preservation medium, is reported to extend the period of cold storage. In order to evaluate the efficacy of UW solution in human liver preservation we compared 58 donor liver grafts preserved in Euro-Collins (EC) solution. All livers were harvested in a similar manner. Donor and recipient characteristics in the two groups were comparable. The mean preservation time of the UW solution was 11.5 +/- 4.2 hr (range 3-20 hr), significantly longer than the EC mean preservation time of 4.9 +/- 1.6 hr (2-9.6 hr) (P = 0.0001). Evaluation of mean postoperative liver function tests and coagulation factors on days 1-7 showed no statistical difference between the two groups. There was one primary graft nonfunction in the EC group and none with the UW organs. Hepatic artery thrombosis was similar in each group. The incidence of early retransplantation was similar. Three-month graft survival was 81% in the UW group vs. 73% in the EC group. Patient survival at three months was 87% with the UW organs and 84% with the EC organs. We conclude that cold storage of liver grafts in the UW solution has allowed for significantly longer preservation, permitting transplantation to be performed under semielective conditions and procurement of organs from much further distances. Grafts stored in UW solution perform as well as those stored in Euro-Collins, with no significant difference in liver function abnormalities postoperatively. PMID- 2305458 TI - An approach to organ salvage from non-heartbeating cadaver donors under existing legal and ethical requirements for transplantation. AB - Effective utilization of nonheartbeating cadaver donor organs is limited by the time required to obtain the necessary family consent prior to organ retrieval (a delay of at least 4-6 hr); this exceeds by far the maximum tolerance of kidneys to warm ischemia. Measures that could theoretically permit use of such organs include: (1) rapid in situ flush cooling; (2) continued in situ kidney cooling until permission for donation is secured; and (3) cell-membrane stabilization of vital organs, with only minimal invasion of the donor body. These measures were tested experimentally in dogs. Hemorrhagic shock was produced in mongrel dogs. One hour after cessation of heartbeat, a rapid perfusion tube was placed into the femoral artery; it was advanced, and its balloon was inflated in the aorta above the renal vessels. The kidneys were then flushed in situ with 1000 cc of cold preservation solution containing a calmodulin inhibitor, trifluoperazine. Two other catheters were inserted percutaneously into the peritoneal cavity for continuous intraperitoneal cold perfusion. Core temperatures of 4 degrees C were maintained in situ in the kidneys for 5 hr. Six hours after cardiac arrest, the kidneys were removed and preserved ex vivo at 4 degrees C for 24 hr, and were then transplanted into their respective hosts (n = 11), where they sustained life uneventfully. This method requires a 2-inch incision in the groin of the prospective donor, and two small stab wounds of the abdomen; i.e., semi-invasive procedures which are commonly performed in emergency rooms. The perfused body could then be released to the family if donation is denied. The recently documented increased willingness of the public to donate organs when the termination of life support is not an issue, and court decisions that have authorized the performance of nondeforming diagnostic procedures in cadavers without consent, suggest that the salvage of transplantable semi-invasive procedures described in this study may be useful in helping to alleviate the current shortage of transplantable organs. This technique can provide the time needed for families to consider the option of organ donation from nonheartbeating cadaver donors in an unhurried and unpressured manner, while preserving the viability of vital organs during the decision-making process. PMID- 2305459 TI - Influence of preservation time on outcome and metabolic function of bladder drained pancreas transplants. AB - The influence of cold storage preservation time on graft survival and metabolic function of pancreatic transplants was studied in 130 recipients of bladder drained grafts (47 simultaneous with, 33 after, and 50 without a kidney transplant) between October 1, 1984 and May 1, 1989. The recipients were divided into four groups according to the preservation time: less than 6 hr (n = 11), 6 12 hr (n = 24), 12-24 hr (n = 75), and greater than 24 hr (n = 20). Twenty-six grafts were procured by other transplant teams and sent to us. Silica gel fractionated plasma was used for preservation in 104 cases and the University of Wisconsin solution in 25 (1 in the less than 6 hr, 2 in the 6-12 hr, 16 in the 12 24 hr, and 6 in the greater than 24 hr groups). The technical failure rate at 1 month was 13% (17 grafts), 1 (9%) in the less than 6 hr, 5 (21%) in the 6-12 hr, 9 (12%) in the 12-24 hr, and 2 (10%) in the greater than 24 hr groups. At 1 month, 107 (82%) of the grafts were functioning, 10 (91%) in the less than 6 hr, 18 (75%) in the 6-12 hr, 62 (83%) in the 12-24 hr and 17 (85%) in the greater than 24 hr groups, the longest preserved for 30 hr. The respective 1-year graft survival rates were 51%, 50%, 57%, and 70%. Ninety patients (10 in the less than 6 hr, 16 in the 6-12 hr, 51 in the 12-24 hr, and 13 in the greater than 24 hr groups) had metabolic studies between 2 and 6 weeks postransplant. The results of 24-hour profiles (14 blood glucose determinations) were similar in each preservation time group; the means of the mean (+/- SD) profile glucose (mg/dl) values were 130 +/- 19, 126 +/- 31, 130 +/- 24, and 129 +/- 30, respectively (P greater than 0.6). Mean plasma glucose levels at 2 hr during OGTT were 141 +/- 32, 145 +/- 43. 163 +/- 49, and 184 +/- 100 in the respective preservation groups (P greater than or equal to 0.064). According to the National Diabetes Data Group classification, 75% of recipients in the less than 6 hr, 50% in the 6-12 hr, 44% in the 12-24 hr, and 33% in the greater than 24 hr groups had normal OGTT results.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2305460 TI - Heart transplantation in diabetic recipients. AB - Preexisting diabetes mellitus (DM) has been regarded as a contraindication to heart transplantation (HT). This prejudice has been based upon concern over increased infection rates and worsening DM with the initiation of prednisone immunosuppression. To better evaluate these suppositions, we reviewed our experience with diabetic patients who underwent HT. Between 6/80 and 1/88, 367 nondiabetics (NDs) and 19 diabetics underwent HT at our institution. Of the 19 diabetic recipients (DRs), two were black and four were female. Six DRs were on insulin (average daily dose: 46 U) prior to HT, and the remainder required oral hypoglycemic agents. Following HT, five DRs had insulin substituted for oral hypoglycemics. The 11 insulin-dependent DRs now require an average daily dose of 48 U. The average duration of follow-up for the 19 DRs was 17 months (range 1-67 months). During this time, 5 hospitalizations were required for complications of diabetes. The rejection rate was not higher for the DRs than the NDs (0.37 events/100 pt. days vs. 0.51 events/100 pt. days). The DRs who have undergone coronary angiography up to 4 years following HT have had no evidence of coronary atherosclerosis. Three-year survival for DRs and NDs is similar. DRs have a slightly higher incidence of lethal infections than NDs, which is not statistically significant (16% at 17 months vs. 10% (p greater than 0.4). We conclude that carefully selected diabetics can undergo HT with minimal consequent worsening of their DM. Diabetic HT recipients do not suffer a higher incidence of graft atherosclerosis, rejection, or lethal infection. PMID- 2305461 TI - Improved cardiac allograft function following triiodothyronine therapy to both donor and recipient. AB - Brain death is associated with neuroendocrine changes, in particular with a significant reduction of plasma-free triiodothyronine (T3) that results in impaired aerobic metabolism. Myocardial energy stores are reduced and tissue lactate increased. Cardiac function deteriorates. Similar metabolic changes are seen in patients undergoing open-heart surgery on cardiopulmonary bypass, including those undergoing heart transplantation. Therapy with T3 leads to a reversal of these metabolic changes, resulting in improved cardiac function. One hundred and sixteen consecutive potential donors have been so treated, as have 70 of the recipients. Immediate posttransplant cardiac function was good in all but 3, and these hearts recovered to normal within a maximum of 24 hr of mechanical support. In 2 small randomized trials in patients undergoing myocardial revascularization on cardiopulmonary bypass, postoperative T3 therapy was associated with a reduced need for inotropic support and diuretic therapy in the first study and improved cardiac output in the second study. PMID- 2305462 TI - Childbearing after liver transplantation. AB - Seventeen female patients who underwent orthotopic liver transplantation between June 1973 and June 1987 became pregnant 5 months to 11 years after transplantation. Immunosuppression was maintained with combinations of prednisone, cyclosporine, and azathioprine prior to and during pregnancy. One patient discontinued immunosuppression after knowledge of pregnancy, taking only azathioprine sporadically. Mean age at time of delivery was 26 years. Twelve patients had no alteration in liver function studies; 7 patients demonstrated mild or moderate enzyme elevations prior to delivery, with one case of rejection confirmed by percutaneous liver biopsy. Major problems related to pregnancy were hypertension, anemia, and hyperbilirubinemia. Twenty live births occurred (2 patients had 2 separate pregnancies, one patient had a set of twins); 13 were by cesarean section, 7 by vaginal delivery. Eleven of the 13 cesarean births were premature by gestational age. All vaginal births were term. Toxemia of pregnancy and early rupture of membranes were the principal indications for cesarean section. There were no congenital abnormalities or birth defects and all the children are surviving well. Fifteen of 16 children older than one year all have normal physical and mental development, with one child manifesting immature speech development. Four children are under one year, all with normal milestones thus far. Sixteen of the 17 mothers are alive from 2-18 years after transplantation; the only death was from a lymphoma, almost 4 years after transplantation and 2 1/2 years after delivery. This experience suggests that women undergoing liver transplantation can safely bear children despite an increased risk of premature cesarean births. The effect of chronic immunosuppression of female pediatric patients on their reproductive potential later in adulthood remains to be fully evaluated but the results so far are favorable. PMID- 2305463 TI - Evidence that zero antigen-matched cyclosporine-treated renal transplant recipients have graft survival equal to that of matched recipients. Reevaluation of points. AB - The value of HLA matching in cadaver renal transplantation (CRT) continues to be debated. It has recently been suggested that increased importance be given to HLA matching for the distribution of cadaver kidneys. Such a policy would add both delay and expense to CRT, which could be justified only by significantly improved results. The results of CRT in 252 cyclosporine treated adult patients transplanted at our institution from November 1984 to April 1989 were reviewed. Kidneys were initially transplanted into crossmatch-negative recipients based on waiting time, regardless of match. From October 1987, a points system, based on United Network for Organ Sharing (UNOS) criteria has been used. Eighty-four pts. with zero antigen match with their donors were compared with 168 pts. sharing 1-6 Ag. Actuarial graft and patient survival were determined by the cumulative life table method and compared using a log rank test. Our results indicated no statistically significant difference in graft survival because of better matching or mismatching. These findings are in keeping with our previously reported long term results for non-CsA pts. Past predictions of improved graft survival based upon better matching at our institution have not fulfilled expectations, with the exception of 6 Ag matches. In conclusion, increased emphasis on HLA matching with fewer "points" for poorer matches does not appear justifiable. PMID- 2305464 TI - Causes of graft loss beyond two years in the cyclosporine era. AB - While CsA has improved renal-allograft survival rates in the first 2 years compared with Aza, Terasaki's multicenter study (1) failed to show any difference in long-term graft survival in CsA-Pred versus Aza-Pred-treated recipients. The present study examines the long-term graft-survival rates at a single center using CsA immunosuppression and seeks to discern the causes of 58 graft losses among 343 patients with functioning grafts beyond 2 years posttransplantation. The 6-year primary and cadaveric actuarial graft survival at this institution is 59% with a graft half-life of 10 years, which is better than the 40% and 7.7 years, respectively, reported by Terasaki (1) for primary cadaveric recipients on Aza-Pred. It is also better than the 41%, 6-year survival and 5.5-year half-life for primary cadaveric recipients treated with CsA-Pred as reported in the multicenter study. (1) Less experience with the use of CsA may explain the latter comparison. Primary LRD grafts at this institution (2/3 haploidentical) have a 6 year actuarial survival of 77% and a half-life very closely approximating that of HLA-identical LRD grafts under Aza (23.4 years). These results demonstrate that CsA mitigates the effects of HLA incompatibility to reduce graft survival. The most common cause of graft loss beyond 2 years was chronic rejection (36.2%) followed by noncompliance (27.6%). Patient deaths resulted in 13 of the 58 graft losses; most of the deaths were related to cardiovascular diseases. Only 3 patients died from causes that could be attributed to CsA immunosuppression; 2 from sepsis and 1 from viral hepatitis. Acute rejection caused 8.6% of the graft losses on continuous CsA therapy. When immunologic risk factors were analyzed, the entire graft-loss group had a significantly higher proportion of retransplant patients than the graft-survival group (P less than 0.005), suggesting that prior transplantation imposes a higher risk for graft loss not only acutely but long term as well. However, retransplanted patients were significantly less likely to lose their grafts because of noncompliance (P less than 0.005). Male patients were found to be significantly more noncompliant. PMID- 2305465 TI - Transplantation in HIV+ patients. AB - Twenty-five whole-organ recipients treated from 1981 through September 1988 were HIV carriers. Eleven were infected before transplantation, although this was not known until later in 8 recipients. The other 14 were infected perioperatively. Ten of the 25 recipients were infants or children. The organs transplanted were the liver (n = 15), and the heart or kidney (n = 5, each). After a mean follow-up of 2.75 years (range, 0.7-6.6 years), 13 recipients are alive. Survival is 7/15, 2/5, and 4/5 of the liver, heart, and kidney recipients, respectively. The best results were in the pediatric group (70% survival) in which only 1 of 10 patients died of AIDS. In contrast, AIDS caused the death of 5 of 15 adult recipients and was the leading cause of death. Transplantation plus immunosuppression appeared to shorten the AIDS-free time in HIV+ patients as compared to nontransplant hemophiliac and transfusion control groups. Accrual of HIV+ transplant recipients has slowed markedly since the systematic screening of donors, recipients, and blood products was begun in 1985. PMID- 2305466 TI - The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era. AB - Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation. PMID- 2305467 TI - Noncompliance in organ transplant recipients. AB - Noncompliance with medication and follow-up care was evaluated in 538 renal, 50 heart, and 13 liver transplant recipients. In a retrospective review of 260 kidney transplant recipients followed from three months posttransplant, the incidence of medication noncompliance was 18%. It was 15% in a prospective study of 196 kidney recipients from 1984 to 1987. Patients most likely to become noncompliant were young and in a lower socioeconomic group. There was no significant difference in the incidence of noncompliance with respect to cadaveric vs. living-related donor kidney source, or in male vs. female patients. There was a higher incidence of noncompliance in blacks and Hispanics, but that may have been due to a higher incidence of lower socioeconomic status in those groups. Noncompliance can occur many years posttransplant and was seen in heart and liver transplant recipients. In the retrospective study, 91% of kidney transplant recipients who were noncompliant with medications and follow-up care either lost their grafts or died. Noncompliant behavior was usually not predictable and was often without an identifiable reason. Efforts to increase compliance, such as better patient selection, more education, and simplified medical regimens may have reduced the incidence of noncompliance in recent patients. PMID- 2305468 TI - The use of older donor livers for hepatic transplantation. AB - The function and outcome of liver grafts from "older" donors (more than 50 years old) were compared with grafts from younger donors (less than 50 years old). Of 184 consecutive liver transplants, 23 grafts were from older donors (50.2-65.3 years, mean 54.3 years). The liver preservation period was short, averaging less than 4 hr with the maximum under 8 hr for the older grafts. The majority of livers were preserved with Collins' solution. All transplants were performed using consistent methods that had proved to be successful over time. The medical status of the patients who received the older and younger grafts was similar but a higher percentage of older grafts were transplanted into ABO blood group- incompatible recipients. Graft function--as determined by peak aminotransferase levels, duration of prolonged prothrombin time, retransplantation rate within 30 days and incidence of primary nonfunction--was not significantly different in older versus younger grafts. Actual 30-day graft survival was 86.9% in the older grafts and 85.1% in the younger grafts. Actuarial 1-year graft and patient survival rates were 65.0% and 71.4%, respectively, in recipients of older grafts and 68.8% and 75.6%, respectively, in recipients of younger grafts. It is concluded that donor livers older than 50 years can be transplanted with the same success as younger livers provided that other generally accepted donor criteria are satisfied and the preservation period is short. The upper age limit for liver donation is not yet known. PMID- 2305471 TI - Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow. AB - Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products. PMID- 2305469 TI - Obesity as a risk factor following cadaveric renal transplantation. AB - Obesity has generally been thought to increase the risk of operative mortality and postoperative complications in surgical patients. No data examining obesity as a factor in cadaveric renal transplantation were available. We therefore matched obese patients undergoing cadaveric renal transplantation with nonobese control patients and retrospectively analyzed mortality, morbidity, and graft survival in each group. Patients were matched for age, sex, diabetes mellitus, PRA, graft number, cardiovascular disease, date of transplantation, and posttransplant immunosuppression. There were significant differences found in mortality (11% in obese vs. 2% in nonobese patients, P less than or equal to 0.01), immediate graft function (38% in obese vs. 64% in nonobese patients, P less than or equal to 0.01), 1-year graft survival (66% in obese vs. 84% in nonobese patients, P less than or equal to 0.05), and postoperative complications. Wound complications (20% vs. 2%, P less than or equal to 0.01), intensive-care-unit admissions (10% vs. 2%, P less than or equal to 0.01), reintubations (16% vs. 2%, P less than or equal to 0.03), and new-onset diabetes (12% vs. 0%, P less than or equal to 0.02) were all significantly more common in the obese group. These results suggest that an attempt at significant weight reduction is indicated in obese patients prior to renal transplantation. PMID- 2305472 TI - Induction of MHC class II expression in recipient tissues caused by allograft rejection. AB - MHC class II antigens (DR) are not commonly expressed on parenchymal cells of kidney and liver except when they are allografts undergoing rejection. The objective of this study was to determine whether allograft rejection can also induce DR upregulation in parenchymal cells of autologous recipient organs. Dogs had unilateral renal autografts to facilitate kidney sampling. All kidneys were tubular cell DR-negative. After 8-14 days each dog received a tubular cell DR negative allograft. Tubular cell DR became positive in both allograft and autograft simultaneously, its onset and intensity correlating with blast cell infiltration and rejection in the allograft. Blast cells were first detected in the autograft after allograft nephrectomy, and then disappeared as autograft tubular cell DR diminished over the next 6-8 days. This was reproduced on repeat allografting. In 2 untreated dogs hepatocytes became positive on day 4, with no hepatic blast infiltrate. Four other dogs received cyclosporine immunosuppression. Allograft and autograft tubular cell DR, and hepatocyte DR, increased in all dogs, but were delayed while on CsA until onset of rejection despite transient earlier allograft blast infiltration. Downregulation in autograft and liver occurred together after allograft nephrectomy. An interferon like substance appeared in plasma after allografting in association with the DR changes in native kidney and liver. Renal allorejection therefore induces upregulation of parenchymal DR expression in autologous liver and kidney of the recipient. It is probably mediated by an interferon-like substance derived from cells infiltrating the allograft. The effect is modified by CsA. PMID- 2305473 TI - Malignant disease in childhood in the tropics. PMID- 2305470 TI - Chronic cyclosporine-induced nephropathy in the rat. A medullary ray and inner stripe injury. AB - Cyclosporine CsA nephrotoxicity was examined in male Sprague-Dawley rats with or without prior uninephrectomy, injected daily with 12.5 mg/kg CsA, and fed a salt depleted or normal diet for 3-10 weeks. Control rats received the CsA vehicle. CsA induced a fall in creatinine clearance in salt-depleted rats, from 1.3 +/- 0.1 to 0.8 +/- 0.1 ml/min (P less than 0.001), and in normally fed rats from 1.8 +/- 0.2 to 1.0 +/- 0.2 ml/min (P less than 0.02). Vehicle treatment had no effect. The most striking morphologic changes were those of thick ascending limb cell atrophy with concomitant fibroblastic proliferation and collagen formation; these alterations were present in the inner stripe of the outer medulla and the medullary ray. The medullary-ray findings included S2-S3 degenerative changes as well and apparently correspond to the striped fibrosis described in human CsA nephropathy. The alterations were specific to the CsA group, progressive, and most severe in the salt-depleted, CsA-injected rats (on a scale of 0-4: 1.7 +/- 0.2 for medullary rays, and 2.0 +/- 0.2 for inner stripe, P less than 0.001). Morphologic changes predicted renal failure (r = 0.3, P less than 0.01 for cortical alterations, and r = 0.5, P less than 0.001 for medullary alterations). Prior uninephrectomy did not enhance these changes. Thus, chronic CsA administration impaired kidney function and induced morphologic alterations found in regions characterized by, and in nephron segments particularly vulnerable to, limited O2 availability. Salt depletion appears to accelerate the development of chronic CsA renal injury in the rat. PMID- 2305474 TI - Diagnosis of Burkitt's lymphoma. PMID- 2305475 TI - Feasibility of outpatient surgery in the tropics. AB - The feasibility of outpatient surgery was investigated at a regional hospital in a Third World country. A series of 73 patients with uncomplicated hernias (inguinal, femoral) and hydroceles were allocated at random to receive standard surgical treatment either as inpatients (group 1) or as outpatients (group 2). Patients living within a 4 km radius of the hospital or who agreed to stay in specially provided quarters nearby were eligible to take part in the study. Patients not able to follow the basic hygiene rules taught by the local staff were excluded. The morbidity rate was 5/36 (13.8%) in group 1 and 8/37 (21.6%) in group 2. No statistically significant differences were demonstrated between the complications that occurred in the two groups. PMID- 2305476 TI - Use of antenatal cards for literate health personnel and illiterate traditional birth attendants: an overview. AB - A review of the existing literature on various risk-oriented antenatal cards developed during the last 15 years, makes apparent a multitude of action-oriented cards available for trained health personnel (obstetric nurses, midwives and doctors). Few antenatal cards, however, have been developed for use by illiterate traditional birth attendants (TBAs). A revised version of an illiterate antenatal card is presented, that has been developed over the past 3 years in Mali. It contains some important improvements, notably its use at the various levels of the health care pyramid both by illiterate TBAs and by trained midwives. It also includes specific 'standing orders', based on generally accepted 'at-risk' criteria. Suggestions for its adaptation elsewhere in Africa as part of current Safe Motherhood policies are discussed. PMID- 2305477 TI - Do the benefits of breastfeeding outweigh the risk of postnatal transmission of HIV via breastmilk? AB - Conflicting recommendations have been offered about whether HIV+ mothers should breastfeed. Since there is a strong precedent for US infant feeding practices to be imitated in developing countries, a model was constructed to estimate infant mortality if the CDC admonition for HIV+ mothers not to breastfeed were upheld in less developed settings. Estimates are given for infant mortality in the presence and absence of breastfeeding across several baseline levels of infant mortality and across several theoretical rates of transmission through breastfeeding. The infant mortality associated with HIV infection acquired through breastfeeding is estimated to be lower than the mortality associated with the diseases of infancy that would result if breastmilk were withheld. The difference in these estimates is greater in areas with high baseline levels of infant mortality. PMID- 2305478 TI - Teeth cleaning habits of children in rural villages in Telengana area, south India. PMID- 2305479 TI - Using a simple protocol for cord prolapse. PMID- 2305480 TI - Mats instead of sheets on hospital beds. PMID- 2305481 TI - Nursing wounds with salty water. PMID- 2305482 TI - International Foundation for Dermatology. PMID- 2305483 TI - Retinoblastoma in Zaire. PMID- 2305484 TI - Septic complications of 100 abdominal deliveries in the rural tropics. PMID- 2305485 TI - Traditional child health practices in communities in north-west Ethiopia. PMID- 2305486 TI - Postoperative dressings: are they really necessary? PMID- 2305487 TI - HIV: implications for blood transfusion and banking in Africa. PMID- 2305488 TI - An endometriotic cyst of the left ovary in pregnancy. PMID- 2305489 TI - Gravid uterus in an anterior abdominal wall hernia of a Nigerian woman. PMID- 2305490 TI - Abacterial cystitis in urinary incontinent females. AB - Among the number of urological symptoms in women complaining of incontinence more specific symptoms are often overlooked. Frequency, urge, suprapubic pain, nocturia, etc., are typical for bladder wall disorders, but also often misleading as part of the incontinence symptomatology. The final diagnosis of bladder wall diseases is based on biopsies from the bladder wall. It is noteworthy that the mucosa often looks normal at endoscopy. In this paper several types of abacterial cystitis will be presented to illustrate the difficulty in revealing the diagnosis of bladder wall disorders. PMID- 2305491 TI - Relation between calcium oxalate hydrate form found in renal calculi and some urinary parameters. AB - In calcium oxalate urolithiasis, the monohydrate and dihydrate forms can be found. The aim of this paper is to examine a group of patients with calcium oxalate calculi to determine the calcium oxalate form and the possible relationship with calcium and other urinary biochemical parameters. It was found that calcium oxalate monohydrate is more frequent in the normocalciuric group and also is associated with a lack of inhibitory capacity, while a mixed calculus of calcium oxalate and phosphate or calcium oxalate dihydrate can be related with hypercalciuria. PMID- 2305492 TI - Magnetic resonance imaging of acute and long-term alterations following extracorporeal shock wave lithotripsy in rats. AB - The kidneys of 30 rats were treated by extracorporeal shock wave lithotripsy (ESWL) with different doses of extracorporeal shock waves: 500, 1,000 and 2,000. The animals were sacrificed after 24 h, 7, 14 or 35 days. Magnetic resonance (MR) imaging at 1.5T was used to evaluate the effects of ESWL on T1- and T2-weighted (spin echo 600/22, 1,600-2,000/90) images compared to histology and macroscopy. The severity of pathologic changes correlated dose dependently with the number of shock waves given (500-2,000). The MR findings following ESWL in 50 kidneys included diffuse loss of the corticomedullary junction (n = 20), perirenal and subcapsular fluid (n = 23), intrarenal foci of increased (n = 16) or decreased (n = 8) signal intensity, and loss of distinction between renal, splenic or hepatic contours (n = 7), detected macroscopically as adhesions. Subcapsular and intrarenal findings corresponded to acute hematomas and organized fibrotic tissue morphologically. In long-term groups MR revealed fibrotic shrinkage of the renal convexity as indentation of the kidney surface (n = 12). MR imaging is a sensitive method for the detection of specific alterations following ESWL, especially intrarenal changes, which are important for possible long-term lesions after ESWL. PMID- 2305493 TI - DNA ploidy and S phase fraction in human bladder cancer. Relation to survival and histological grade (WHO). AB - The nuclear DNA content of archival paraffin-embedded bladder cancer samples (70 patients) of WHO grades I-III has been measured by flow cytometry. The female/male ratio was 15/55. The mean follow-up time was 13 years (range 9.6-22.0 years). 37 of 70 (53%) patients had DNA index 1.0 (diploid DNA content), and the remaining 33 (47%) patients had an aneuploid tumor. There was no significant difference in the age (mean +/- SD) of the patients having a diploid (66 +/- 9 years) or an aneuploid tumor (68 +/- 11 years) at the time of diagnosis. 47 deaths occurred during the follow-up period; 24 (51%) of these were due to bladder cancer (12 diploid, 12 aneuploid tumors). No significant difference was found after radical treatment during the disease-free interval (mean +/- SD) between diploid (48 +/- 45 months) and aneuploid (35.5 +/- 35 months) groups of patients. Recurrences during the follow-up period were equally common among aneuploid and diploid tumors. A statistically significant relation between histological grade and survival could be demonstrated, but DNA ploidy and S phase fraction had little prognostic value in this respect. There was no statistically significant difference in survival between aneuploid (30%) and diploid (35%) groups of tumors during the follow-up period. The study suggests that flow cytometric determination of nuclear DNA ploidy from paraffin-embedded samples in bladder tumors does not add to the prognostic power of subjective histological grading. PMID- 2305494 TI - Remote afterloading transurethral radiotherapy for prostatic cancer. AB - We have developed a technique of transurethral radiotherapy for prostatic cancer using a remote after-loading system. The radioactive source is a cobalt-60 pellet with 3.7-Ci activity. Four patients with adenocarcinoma of the prostate were treated. In all patients, the local tumor response was rapid and satisfactory as judged by physical examination as well as ultrasonography. Serious complications were not seen. A new technique and preliminary clinical results are reported. PMID- 2305495 TI - Meshgraft urethroplasty using split-thickness skin graft. AB - Meshgraft urethroplasty has become one of the standard operative procedures for the treatment of long and complicated urethral strictures. The original method used meshed foreskin for urethral reconstruction. To extend the application of the method to circumcized patients, a split-thickness skin graft was used to construct a neo-urethra. In a first stage, a split thickness skin graft is harvested from the medical part of the thigh and transplanted alongside the opened urethra. After complete healing of this transplant, the neo-urethra is formed in a second stage 12 weeks later. Since 1980 meshgraft urethroplasty using a split-thickness skin graft has been performed in 34 patients. In all patients excellent anatomic and functional results have been achieved. This technique was found to be most useful in exccedingly long or problematic strictures, e.g. in spinal cord-injured patients. PMID- 2305496 TI - Early site of lymphatic involvement from right renal cell carcinoma: CT demonstration and method of lymphadenectomy. AB - The value of lymphadenectomy in the treatment of renal cell carcinoma remains controversial. The precise location of nodal metastasis and method of lymphadenectomy had seldom been mentioned. We report 2 patients with right renal cell carcinoma who had regional lymph node involvement without blood-borne metastasis. The involved lymph nodes were demonstrated by CT scan just behind the inferior vena cava at the level of renal hilus. These nodes seemed to be the first sites of nodal involvement from the right renal cell carcinoma. Elevation of the inferior vena cava by dividing its small branches, including a few lumbar veins, was necessary for complete removal of these nodes en bloc with the right kidney. PMID- 2305500 TI - Urologic pearls. PMID- 2305498 TI - Recombinant interleukin-2-induced regression of pulmonary metastasis of renal cell carcinoma. AB - A patient having renal cell carcinoma with multiple pulmonary metastasis was treated with recombinant interleukin-2. Pulmonary metastatic nodes were markedly diminished. The response was maintained for 4 months. At Autopsy, many fibrotic areas in which metastatic carcinoma was thought to have previously existed and then healed were observed in the bilateral pulmonary lobes, although a few microscopically tiny metastatic lesions still remained. PMID- 2305497 TI - Multiple pulmonary metastases from renal cell carcinoma treated effectively by recombinant interleukin-2. AB - A 53-year old male with multiple pulmonary metastases from a renal cell carcinoma was treated with high dose recombinant interleukin-2 (rIL-2). rIL-2 was administered intravenously, and the dose was gradually increased to a subsequent daily dosage of 3 x 10(6) units for a total amount of 470 x 10(6) units. After 3 months, plain chest film and chest computerized tomography revealed a remarkable reduction in pulmonary metastases. There were no side effects except general fatigue and fever. Immunological studies revealed an increase in lymphocytes and enhancement of natural killer activity. These results suggested that rIL-2 is effective for pulmonary metastases from renal cell carcinoma. PMID- 2305499 TI - A rare scrotal mass: fibrous pseudotumor of epididymis. AB - Fibrous pseudotumor, also called multiple fibromata pseudofibromatous periorchitis, is a rare testicular fibromatous condition. It is a benign fibroproliferative lesion with dense hyalinization and sometimes focal calcification. Most of the cases occur in the testicular tunics, whereas a few originate from the epididymis. PMID- 2305501 TI - Techniques of genital examination and bladder catheterization in female children. AB - The physical examination of the female child should not be considered complete until there has been an examination of the external genitalia, but without an effective technique and finesse, this examination can become an ordeal for everyone involved. The examination usually can be conducted with the child in a frog-leg position on the mother's lap. Catheterization can be performed with the child similarly positioned without using gloves, an examination light, or preparatory washing of the genitalia. PMID- 2305502 TI - Endoscopic ureteral occlusion for urinary diversion in patients with lower urinary tract fistulas. AB - Endoscopic ureteral occlusion and nephrostomy drainage is a simple, nonsurgical procedure that can control urine leakage from an intractable lower urinary tract fistula and improve the quality of life for a patient with a short life expectancy. PMID- 2305503 TI - Greenberg surgical support system for the endourologist. AB - As the field of endourology diversifies, the importance of ergonomics grows. The technology developed to assist the endourologist may accomplish the surgical goals effectively, but it often does not consider instrument control, planning of space, and the physical comfort of the operator. The Greenberg retractor creates a surgical environment that improves the urologist's efficiency and technical proficiency. Complex staghorn cases can be performed with reduced risk of inadvertent damage to renal tissue, no shifts of the nephroscope, and a more productive experience for the assistant. PMID- 2305504 TI - Low-profile balloon: superior retention device for catheter drainage of bladder and renal pelvis. AB - The Low-Profile Balloon Catheter has been evaluated in more than 60 patients. It is easily placed in the bladder and renal pelvis. The special design of its disk shaped balloon and large-lumen shaft results in excellent drainage, dependable retention, and a comfortable indwelling drainage tube. PMID- 2305506 TI - Vesicoureteral reflection for ureteral replacement: new operation. AB - In order to preserve the kidney with adequate ureteral length, an operation has been devised in which a flap is developed from the bladder and turned into a tube with the ureterovesical junction and the lowermost segment of the ureter intact and reflected upward, thereby obtaining the needed length with minimal disruption of the blood supply. There is no need for an antireflux reimplantation. This operation, which is most suitable for the replacement of the upper two thirds of the ureter, has been performed in eight dogs with excellent results. PMID- 2305505 TI - Easy method of upper-pole heminephroureterectomy in duplex systems in children. AB - An easy method of upper-pole heminephroureterectomy is described in which a finger is inserted into the dilated upper collecting system, and the upper pole is removed by dissecting directly against the collecting system using finger guidance. This approach prevents entry into the lower-pole collecting system, minimizes blood loss, and maximizes preservation of normal renal tissue. Easy access to the lower ureter through the same incision is facilitated by the use of the Sims vaginal retractor. PMID- 2305507 TI - Techniques to enhance the ileal conduit. AB - There is a need for operations by which the complications of ileal conduits can be prevented or corrected. The author details techniques to ensure the formation of a short conduit, to shorten a conduit through a peristomal incision, and to correct ileocutaneous stomal stenosis. PMID- 2305508 TI - Cosmetic orchiectomy for prostate cancer. AB - With several effective therapeutic methods available for achieving androgen ablation, we must respect the psychological needs of our patients. The choice should ultimately be made by the patient after a thoughtful discussion of the advantages and disadvantages of various approaches. Cosmetic orchiectomy has the advantages of having the minimal morbidity of a simple operation, achieving the reliable result of androgen ablation and preserving the physical male organ without the risk of drug side effects and the dependence on patient compliance. In our experience, the operation is satisfactory both in achieving the therapeutic goal of androgen deprivation and in meeting the psychological needs of patients. PMID- 2305509 TI - Modified stirrups for dorsal lithotomy positioning. AB - The modified dorsal lithotomy position is excellent for radical pelvic operations. Use of modified Krauss arm supports as stirrups, along with pneumatic devices that intermittently compress the legs, significantly reduces postoperative morbidity in patients who undergo operations in this position. PMID- 2305510 TI - Modifications in operating-table design for urologic microsurgery. AB - Microsurgery, especially on an outpatient basis, is a growing part of urologic practice. A commercial table that matches the exacting requirements of urologic microsurgeons does not exist. We have developed a simple and inexpensive design that can be fabricated easily by a hospital workshop. Notable features include removable arm rests, table indentations, and an x-ray carriage assembly. The table is easy to maintain, transport, and store. Comfort and easy access to the operative field improve the surgeon's performance and ultimately translate into better operative results. PMID- 2305511 TI - Urologic uses of the bed BUG. AB - A Bed Utility Grip can be positioned on the bed frame in whatever place is the most advantageous for such purposes as supporting urinary drainage bags, including double-hanger designs, and the Vitalmetric unit. PMID- 2305513 TI - Update on urinary stone disease. PMID- 2305512 TI - Unitary drainage bag. AB - A urinary bag in which the collection bag is part of a panel that hangs from a belt around the patient's waist avoids local irritation of the thigh and embarrassment of the superficial venous circulation. The bag can be used with nephrostomy and cystostomy tubes as well as urethral catheters. PMID- 2305514 TI - Preventing hematomas during artificial erection. AB - Subcutaneous hematoma can be avoided during artificial erection by placing the injection needle through the glans penis into the corpus cavernosum. Blood from the puncture site in the corpus is then absorbed through the drainage system of the corpus spongiosum. PMID- 2305515 TI - Simplified tourniquet for intracavernous pharmacotherapy. AB - A simplified tourniquet, the Barretta Laso, is described for use during intracavernous injection of vasoactive drugs. The advantages of this device over current tourniquet methods include simple application; easy control of the degree of constriction; and quick, single-handed release. PMID- 2305517 TI - Intraoperative endourologic urethral manipulation. AB - These simple techniques are rapid and efficient ways to deal with intraoperative difficulties. The equipment required is readily available in most operating rooms where endourologic procedures are performed. The techniques can obviate open surgical procedures, thus decreasing the morbidity to the patient and creating significant cost savings for the provider. PMID- 2305516 TI - How to make your patient comfortable and tolerate an indwelling urethral catheter indefinitely. AB - A three-way catheter with openings for local anesthetic application allows patients to tolerate urethral catheters indefinitely. PMID- 2305518 TI - The Goodwin sound: an aid in treating obliterated membranous urethral strictures endoscopically. AB - The treatment options for a man with obliteration of the membranous urethra are many today because of the great progress that has been made in the past 40 years. No one procedure is likely to be ideal for all situations. Pullthrough, two-stage scrotal inlay, and transpubic or perineal approaches can be applied with success. Endoscopic treatment can also be used with satisfactory results and less morbidity in selected patients. A failed endoscopic attempt should not interfere with a subsequent open procedure. Conversely, a failed open procedure may be remedied by endoscopic surgery. We feel our technique is simpler than other reported endoscopic techniques, as it requires only one urologist, and it does not require fluoroscopy or endoscopy from above. Significantly, it provides a guide to cut on that relieves the fear of inadvertent incision into the rectum. PMID- 2305519 TI - Splitting the pubis for exposure in difficult reconstructions for incontinence. AB - We have presented our technique for and experience with splitting the symphysis to provide wide exposure in reconstructive surgery for incontinence. Our experience has demonstrated that the technique is widely applicable to many reconstructive situations in patients of all ages. We believe that spreading the pubic symphysis provides access to the urethra and bladder neck not otherwise possible and regard it as an important factor in the success of many difficult operations to correct incontinence. Although seemingly a radical maneuver, it did not cause complications in any of 51 cases. PMID- 2305520 TI - Exposure of puboprostatic ligaments and dorsal vein complex during radical retropubic prostatectomy. AB - Exposure of the puboprostatic ligaments and underlying vascular structures is facilitated by removal of the Foley catheter and positioning of a Van Buren sound or Roth urethral suture guide in the prostatic urethra. Downward pressure on the sound puts traction on the ligaments and endopelvic fascia, more clearly demonstrating the ligaments and vessels. PMID- 2305521 TI - Large Hegar dilators as prostatic elevator during transurethral resection of the prostate. AB - Large Hegar dilators can be used instead of an index finger through an O'Conner rectal shield to elevate the posterior lobe of the prostate for better access of the resectoscope. The dilators improve maneuverability and provide more length than a finger and are particularly useful in men with marked obesity, arthritic hips, or other conditions that interfere with rectal manipulation of the prostate. PMID- 2305522 TI - Transcervical resection of uterine myomas with a resectoscope. AB - As a surgical option, transcervical resection of uterine myomas is in the early stages of development. Although promising and a logical extension of the increasing reliance on hysteroscopy in gynecology, the comparison with the surgical standards of care for myomas (hysterectomy and hysterotomy) remains incomplete. The safety of the procedure, in the hands of a skillful resectionist, should be equivalent to that of a transurethral prostatectomy or bladder tumor resection. Postoperative management remains anecdotal, however, as the value of perioperative antibiotics, uterine stenting, or the administration of hormones to promote uterine healing has not been established. PMID- 2305523 TI - Use of resectoscope for colon cancer. AB - Urologic endoscopic resectoscopes greatly simplify electrofulguration and resection of rectal tumors. The most important advantage is the enhanced visibility that allows determination of the depth of resection and good hemostasis. The indications for this procedure are otherwise-poor surgical candidates, palliation, excision of locally aggressive tumors such as villous adenomas, and bowel diversion prior to definitive therapy. Bleeding, peritoneal perforation requiring colostomy, and postoperative infection have all been reported, but the complication rate appears to be acceptable. Further clinical studies are necessary to determine if, indeed, this can be considered a curative procedure. Finally, because the practicing urologist is intimately aware of the technical aspects of the urologic resectoscope, he will probably be called on to perform, and should be aware of, this procedure. PMID- 2305525 TI - The guide-eye ureteral access system. AB - Equipping ureteral instruments with the guide-eye feature has expanded the instrumentation options available to urologists. The guide-eye facilitates repetitive instrument access, allows coordinated instrument combinations, and enhances sequential placement of a series of instruments. We believe this concept increases the safety and efficacy of our present instruments and clearly encourages innovative designs for the future. PMID- 2305524 TI - Percutaneous bladder procedures. AB - Endourology must now include lower urinary tract pathology. The above techniques utilize equipment that is readily available in most centers performing percutaneous procedures. As with the upper tract endourology, the procedures performed in the bladder are likely to reduce morbidity and hospital stay, and in fact, many of these procedures are performed in the office setting under local anesthesia. Our experience was initially in the geriatric population but has now expanded widely, and we use this approach primarily in many bladder cases. PMID- 2305526 TI - Controllable stone baskets can capture the elusive ureteral stone. AB - Poor expansion of a spiral stone basket within the ureter often results in failure to engage a ureteral calculus. A special pull-wire incorporated into the design of such a basket facilitates predictable expansion of the basket even when the ureteral lumen seems narrow. Excellent results in capturing and removing ureteral calculi have been achieved with this controllable basket, including stones in several patients in whom standard spiral baskets failed to engage the calculus. PMID- 2305527 TI - New coaxial ureteral stricture knife. AB - Open surgical repair of upper urinary collecting system strictures or obstructions is difficult and is less likely to be accepted by the patient than an endoscopic or ureteroscopic approach. In the hands of an experienced urologic endoscopist the use of our cold blade has the advantage of less trauma to the ureter, already compromised by poor blood supply, than blind dilation; there is visual control of the procedure and acceptance by the patient that the urologic surgeon is doing the procedure; and it is adaptable to rigid or flexible endoscopes and ureterorenoscopes. Furthermore, there is information that the results are better, at least in the short term, than the more traumatic endoscopic procedures associated with dilation. However, only long-term future series will give us an evolving view of this resistant problem. Finally, the ureteral knife we have developed has the potential to be converted to an electrosurgical device for incision or coagulation, when appropriate. An application is pending with the US Food and Drug Administration concerning electrosurgical applications of the ureteral knife (in conjunction with J.R. La Course, PhD, and G.C. Gerhard, PhD, Department of Electrical Engineering and Computer Sciences, University of New Hampshire, Durham). The high dielectric constant of the sheath, combined with hemostatic or incisional properties in this latter mode, would likely prove advantageous. PMID- 2305528 TI - Introducer needle for percutaneous nephrostomy. AB - A new introducer needle that prevents tracking facilitates rapid and predictable entry into the chosen posterior calix with minimal use of fluoroscopy for lithotripsy or renal drainage. This device should make it possible for urologists and radiologists to acquire rapidly the skill to access the kidney in virtually all patients. PMID- 2305529 TI - Percutaneous nephrostomy tract incision using modified Otis urethrotome. AB - An Otis urethrotome has been modified to permit passage into the kidney over an 0.038-inch guidewire by drilling a 3/16-inch hole through the tip. I have used this instrument to aid in the performance of 36 nephrostomy tract dilations without significant complications. When compared with 20 Amplatz tract nephrostomy dilations, the new method was quicker, requiring 4.3 minutes versus 6.5 minutes. This instrument is especially useful for tracts where significant renal fascial scarring makes Amplatz dilation difficult. Ease of tract dilation, as well as decreased time to dilate, make this technique a useful addition to standard nephrostomy tract dilation techniques. PMID- 2305530 TI - Supracostal approach for percutaneous ultrasonic lithotripsy. AB - The supracostal approach to renal access for ultrasonic lithotripsy continues to be used with good results at The Oregon Health Sciences University when indicated, because it provides better access to much of the kidney collecting system and proximal ureter. The complication rate is acceptably low if the precautions outlined above are followed. Access above the 11th rib is discouraged unless there is no other choice. PMID- 2305531 TI - Female bladder neck incision. AB - Bladder neck resection or incision in the female is not a new urologic procedure; however, it has not been widely accepted because of poor results and complications. From January to December, 1986, ten such operations have been performed on females with obstructive uropathy. All had previous anti incontinence procedures and postoperative obstruction developed. Bladder neck incisions rather than resections have been performed with encouraging results. Urologic presentation, urodynamic investigations, and details of the surgery are presented. Bladder neck incision is a valuable adjunct in the management of bladder neck obstruction in the female. PMID- 2305532 TI - Long-term serum creatinine values after radical nephrectomy. AB - Both pre- and postnephrectomy levels of serum creatinine were measured in 52 consecutive patients who underwent radical nephrectomy for localized renal cell carcinoma between 1971 and 1976. At the time of follow-up, 17 patients were alive and 35 had died, 14 of renal cell carcinoma and 21 of other causes. Follow-up lasted a minimum of 115.5 months (mean 151.1 months, median 141.1, range 115.5 211.3 months) for 16 of the 17 patients who were alive. In this group only 2 patients had elevations in the serum creatinine level above 1.6 mg/dL-1.9 mg/dL and 2.4 mg/dL, respectively. The patient whose value was 2.4 mg/dL was a diabetic who required insulin. No serious renal failure, renal disease, or tumors in the contralateral kidney occurred among the total group of 52 patients. These data indicate that renal function remains adequate in patients who have a normal contralateral kidney and are treated by radical nephrectomy. PMID- 2305533 TI - Endoscopic management of urethral stricture: "cut to the light" procedure. AB - Traumatic and iatrogenic urethral strictures present serious management difficulties. Classically their repair has been done through transpubic or perineal approaches. We have investigated the endoscopic route. In this study, 6 patients with dense posterior urethral strictures were managed endoscopically. The results of this "cut to the light" technique compare favorably with the more elaborate open procedures. The operation can be performed easily and carries very low morbidity. PMID- 2305534 TI - Microsurgical treatment of varicocele: selecting most appropriate shunt. AB - Microsurgical drainage of spermatic veins tailored to the hemodynamic type of varicocele was performed in 20 patients. In 14 cases the procedure was indicated as prophylaxis and in 6 cases as treatment of infertility. Complete regression of varicosities was observed in 75 percent as early as six days postoperatively, in 85 percent at two weeks, and in 90 percent at twelve months. In the remaining 10 percent, a consistent reduction of varicocele was found. No patient experienced progression of the disease. Eighty-three percent of the patients with altered seminal parameters showed an improvement of them at a mean follow-up of 9.1 months. PMID- 2305536 TI - Insertion of testicular prosthesis: use of vaginal speculum. AB - We have used a vaginal speculum to insert a testicular prosthesis through the inguinal approach over the past four years. We have found this technique to be easily performed and reproducible in allowing the testicular prosthesis to be placed in the normal dependent position in the scrotum. PMID- 2305535 TI - Cadaveric dura mater graft for correction of penile curvature in Peyronie disease. AB - The use of autologous human dura mater as a graft material in 7 cases of Peyronie disease is described. In 3 cases, preoperative erectile ability was thought to be inadequate, and a penile prosthesis was simultaneously inserted. No complications occurred related to the graft material although 1 patient has inadequate erections postoperatively and another appears to have recurrent Peyronie disease. PMID- 2305537 TI - Frenular chordee: implications and treatment. AB - Twenty of 75 male children undergoing elective circumcision demonstrated a ventral glandular chordee produced by an unusually prominent frenulum. Surgical incision of this prominent band of tissue relaxed the glandular traction (chordee), more adequately exposing the ventral inner prepuce, facilitating skin incisions, and permitting an improved cosmetic and functional outcome. PMID- 2305538 TI - Bilateral synchronous neonatal torsion of spermatic cord. AB - A case of synchronous bilateral spermatic cord torsion in a neonate is presented. While testicular salvage is variable in this entity, surgical intervention is necessary for any hope of testicular preservation. PMID- 2305539 TI - Large perirenal hematoma after extracorporeal shock-wave lithotripsy. AB - We report a case of a large perirenal hematoma following extracorporeal shock wave lithotripsy (ESWL) that resulted in compromised renal blood flow and function and necessitated open surgical drainage. Caution is advised and close follow-up recommended in patients who have taken aspirin-containing compounds, are elderly, have hypertension, or exhibit a significant drop in hematocrit following ESWL. PMID- 2305540 TI - Use of stone brush for treatment of impacted stones in association with extracorporeal shock-wave lithotripsy. AB - A new device is described which enhances the treatment of impacted stones in association with the extracorporeal shock-wave lithotripsy. This technique may result in decreased number of shocks and increased efficiency, as well as, enhance outpatient treatment. PMID- 2305541 TI - Local hyperthermia to canine prostate. A pilot study. AB - Repeated treatments of localized deep microwave hyperthermia were given to a series of dogs by means of a 915 MHz, water-cooled skirt-type applicator. The applicator was inserted into the rectum and directed toward the prostate in order to heat it by means of the absorbed microwaves while keeping the rectal wall at a lower temperature by surface cooling of the applicator itself. Sessions were given for different lengths of time ranging between ninety minutes and five hours, during which the prostate temperature was kept at 42.5 degrees C (+/- 0.5 degrees C) or 44.5 degrees C (+/- 0.5 degrees C). Three-dimensional temperature distributions in the prostate were measured accurately and verified by a Luxtron Fluoroptic Unit. Temperatures were constantly monitored in the rectal wall and in the prostatic urethra. Thorough and systemic follow-up was done before, during, and after each treatment, and the observations are reported. Two interesting preliminary observations were made: (1) differential blood counts showed significantly monocytosis following the treatments and lasted for at least one week, and (2) values of creatinine phosphokinase (CPK) and serum glutamic oxaloacetic transaminase (SGOT) were found to rise irreversibly in those animals which were later found to have definite histopathologic evidence of localized necrotic damage. PMID- 2305542 TI - Renal hematuria caused by "nutcracker" phenomenon: a more logical surgical management. AB - A case of renal hematuria caused by the "nutcracker" phenomenon in a young man is reported. Resection of a preaortic fibrous tissue, renocaval venous reimplantation, and placement of a synthetic wedge into the bifurcation of the superior mesenteric artery were performed to resume an unstagnant flow of the left renal vein. PMID- 2305543 TI - Special retractors for varicocele and infrapubic incisions. PMID- 2305544 TI - Transurethral removal of eroding permanent suture after endoscopic bladder neck suspension. PMID- 2305545 TI - Comparison of the effect of various chemical stabilizers and lyophilization cycles on the thermostability of a Vero cell-adapted rinderpest vaccine. AB - The thermostability of a rinderpest vaccine produced on Vero cells was evaluated using a variety of chemical stabilizers and lyophilization protocols. Three stabilizer preparations and three lyophilization schedules were examined using accelerated stability testing at 37 degrees C. The vaccine preparation exhibiting the greatest stability at 37 degrees C was tested at three additional temperatures, 42, 45 and 56 degrees C, and an Arrhenius plot was constructed from the data. The stability of the reconstituted vaccine produced with the two most efficacious stabilizers was examined using three different diluent preparations. The stabilization method and high Vero cell virus batch titers resulted in a lyophilized vaccine which maintained the minimum required dose of log10 2.5 TCID50 tissue culture infectious dose for more than 20 weeks at 37 degrees C. PMID- 2305546 TI - Polypeptide and antigenic variability among strains of Mycoplasma ovipneumoniae demonstrated by SDS-PAGE and immunoblotting. AB - Comparison of the polypeptide patterns of 22 isolates of M. ovipneumoniae by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a marked degree of heterogeneity with only limited groupings identifiable. Of the 50 major polypeptides identified in one strain (956/2), 35 were shown to be antigenic using immunoblotting with a homologous polyclonal serum. Radioimmune precipitation of 125I-surface-labelled proteins and phase partition using Triton X-114 detergent indicated that these were membrane associated. Cross-reactivity between the isolates was examined by immunoblotting using one polyclonal serum and four monoclonal antibodies (MAbs), all raised against strain 956/2. The polyclonal serum revealed considerable antigenic heterogeneity, but at least nine major antigens were conserved across all isolates. Two MAbs cross-reacted with all 22 strains, but the other two MAbs allowed some differentiation of the strains. One (MO/3) divided the isolates into groups of 16 and 6 based on the presence of absence of a 26-kDa antigen. All strains isolated from sheep with pulmonary adenomatosis fell into the smaller group and did not possess the 26-kDa antigen. PMID- 2305547 TI - Evaluation of an ELISA for the diagnosis of experimentally induced and naturally occurring Leptospira hardjo infections in cattle. AB - An enzyme-linked immunosorbent assay (ELISA) for the diagnosis of Leptospira interrogans serovar hardjo (hardjo) infection in cattle was compared with the microscopic agglutination test (MAT). Glutardialdehyde was used in the ELISA to couple sonicated hardjo antigen to the microtiter plate. Mouse monoclonal anti bovine IgG1 coupled to peroxidase was used as conjugate. Sera from calves experimentally inoculated with hardjo reacted positively in the MAT as early as 10 days after inoculation; these sera did not react positively in the ELISA until 25 days after the first inoculation. Positive and negative field sera from 704 adult cattle on 90 farms were examined by the MAT and the ELISA; a 90% correlation between the two tests was demonstrated. Eighty-six sera from calves inoculated with four Leptospira serogroups other than hardjo and 227 field sera from adult cattle with naturally occurring leptospirosis other than hardjo were examined by the ELISA. Fewer than 1% of these heterologous sera reacted with hardjo antigen in the ELISA. We concluded that the ELISA described in this report is an advantageous alternative to the MAT for diagnosing leptospirosis. PMID- 2305548 TI - Study of TMV assembly with heterologous RNA containing the origin-of-assembly sequence. AB - The assembly of tobacco mosaic virus (TMV) is initiated by a specific reaction between a capsid protein oligomer and an origin-of-assembly region (OAS) located 900 nucleotides from the 3' terminus of virion RNA. Packaging is then completed by rod elongation both in the 5' and 3' directions. The temporal order of the direction of elongation and the characteristics of the reaction were studied by analysis of the in vitro assembly reaction between strain U1 protein oligomers and transcripts containing a strain U1 OAS embedded at different positions in heterologous RNA. The results confirm that elongation in the 5' direction starts very soon after the initiation reaction and is completed rapidly, within minutes. Packaging in the 3' direction is slower and does not appear to commence until 5' rod formation is complete. The reaction of strain U2 protein with the strain U1 OAS initiates rapidly, but elongation occurs only in the 5' direction; 3' packaging does not occur except when the OAS is at or near the 5' terminus, in which case elongation in the 3' direction initiates without delay with either the U1 or U2 protein. Pauses occur during elongation in the 3' direction at an average of 320 nucleotides, indicating a packaging periodicity of about six to eight helical turns. PMID- 2305550 TI - Genetic determinants modulating the pathogenic phenotype of tick-borne orbiviruses. AB - Genetic studies have been carried out on orbiviruses in the Great Island (GI) antigenic subgroup of the Kemerovo serogroup (Orbivrus, Reoviridae) to elucidate the functions of the 10 genomic double-stranded RNA segments. Such studies have shown that segment 4 is the major genetic determinant of neurovirulence (P.A. Nuttall, S.R. Moss, L.D. Jones, and D. Carey, 1989, Virology 172, 428-434), whereas segment 5 of Wexford (WEX) virus and segment 6 of GI virus are the major determinants of serotype specificity (S.R. Moss, C.M. Ayres, and P.A. Nuttall, 1987, Virology 157, 137-144; S.R. Moss, C.M. Ayres, and P.A. Nuttall, 1988, J. Gen. Virol. 69, 2721-2727). In studies with reassortants isolated following dual infection of cell cultures with WEX and GI viruses, the gene combination W4G6 (i.e., viruses deriving segment 4 from WEX virus and segment 6 from GI virus) resulted in nonpathogenic reassortants. Unlike the parental viruses, the avirulent reassortants did not produce clinical evidence of infection in inoculated 2-day-old mice although, suprisingly, they replicated in the brains of the mice. The alternate heterotypic gene combination, G4W5, resulted in typical neurovirulent reassortants. The results indicate that segment 6 of GI virus is able to modulate the phenotypic expression of segment 4 of WEX virus, but not vice versa. Modulation probably results from interactions between the products of these two genomic segments, possibly at the level of virion structure. PMID- 2305551 TI - cis-acting sequences required for in vivo amplification of genomic RNA3 are organized differently in related bromoviruses. AB - Cowpea chlorotic mottle virus (CCMV) is a positive-strand RNA virus that infects dicotyledonous plants. The genome comprises three capped RNAs: RNA1 (3.2 kb), RNA2 (2.9 kb), and RNA3 (2.1 kb). cis-Acting sequences required for amplification in vivo were explored for RNA3, which does not contribute trans-acting factors to viral RNA replication. Using a CCMV cDNA expression system, deletions throughout RNA3 were constructed and tested for successful replication in barley protoplasts coinoculated with RNAs 1 and 2. As previously found for RNA3 of the related brome mosaic virus (BMV) (R. French and P. Ahlquist, 1987, J. Virol. 61, 1457-1465), either of the two coding regions can be individually deleted without blocking RNA3 amplification. However, in striking contrast to BMV, the entire intercistronic noncoding region separating these genes is also dispensable for CCMV RNA3 amplification. Moreover, although simultaneous deletions of the 3a and coat protein genes were deleterious for BMV RNA3 accumulation, CCMV RNA3 derivatives bearing larger deletions encompassing the 3a gene, intercistronic region, and coat protein gene amplify to high levels. Thus, unlike BMV RNA3, cis acting sequences required for CCMV RNA3 amplification map solely in the 5' and 3' noncoding regions. Normal levels of CCMV RNA3 accumulation require over 125 but no more than 220 bases from the 3' noncoding region, and no more than the first 89 bases of the 238-base-long 5' noncoding region. PMID- 2305549 TI - Identification of conserved domains in the cell attachment proteins of the three serotypes of reovirus. AB - Sequence analysis of reovirus serotype 1 (ST1) and 2 (ST2) S1 genome segment cDNAs identified several differences from previously reported versions of their sequences. The sequences reported here comprise 1463 and 1440 base pairs, respectively; for comparison, the ST3 S1 genome segment is 1416 nucleotides long. The serotype 1 and 2 sigma 1 proteins are predicted to contain 470 and 462 amino acids, respectively; the ST3 sigma 1 protein is 455 amino acids long. As previously observed, the ST1 and ST2 sigma 1 proteins are much more closely related to each other than to that of ST3 (about 48 and 25% similarity, respectively, using a computer program that finds about 14% similarity among unrelated proteins). The sequences of the three S1 genome segments have diverged very extensively in all three codon positions, in some cases almost to the extent of randomness. Despite this, not only function but also shape and configuration have been retained (since the three sigma 1 proteins can be incorporated efficiently into completely heterologous capsids). Seventy-nine amino acid residues are conserved among all three serotypes, many of them clustered into five regions in which one-third or more of the residues are triply conserved. These regions may represent functionally conserved domains involved in oligomerization, cell attachment, and hemagglutination. PMID- 2305552 TI - Quantized viral DNA packaging revealed by rotating gel electrophoresis. AB - Two classes of missense mutations in the bacteriophage T4 gene coding for the major head protein produce phage with different length heads. The pt (petite) mutations produce phage with normal, intermediate, and isometric heads, whereas ptg (petite and giant) mutations also produce greatly elongated (giant) heads. DNA from petite, normal, and giant particles was clearly resolved by discontinuous rotating gel electrophoresis, and several new species of headful length DNA were found. These results confirm the idea that the major stop points for head length regulation are at Q = 13, 17, and 21, and also show that minor stop points exist at Q = 16, 18 and 20. The existence of these well-defined classes of DNA that correlate with capsid structure suggest that a structural relationship between the scaffold protein and the capsid protein determines head length and thus DNA length. PMID- 2305553 TI - In vivo analysis of the initiation of bacteriophage T7 DNA replication. AB - We have examined the initiation of bacteriophage T7 DNA replication in vivo using a pulse-labeling technique. The pulse-labeling technique permits the rapid identification of initiation sites on the T7 chromosome and a determination of the rate of movement of the replication fork. This technique has been used to analyze a number of phage mutants having alterations in the nucleotide sequence of the primary origin. The experiments confirm the results obtained by electron microscope analysis on the mapping of the primary origin region and demonstrate the requirement for a T7 promoter in the primary origin. The secondary origins were found to be located near the center and at the right end of the genome. Analysis of T7 phage harboring mutations in the essential replication genes of T7 shows that they fell into three classes. The first, including those mutated in genes 4 and 5, do not initiate DNA synthesis. The second, in genes 3, 6, and 1.2, initiate and elongate as wild-type phage, albeit some with lower rates of synthesis, during the first round of replication and then cease DNA synthesis. Mutations in gene 2 have no apparent effect on initiation or elongation. PMID- 2305554 TI - Sequence analysis of the membrane protein gene of human coronavirus 229E. AB - Human coronaviruses (HCV) are ubiquitous pathogens which cause respiratory, gastrointestinal, and possibly neurological disorders. To better understand the molecular biology of the prototype HCV-229E strain, the complete nucleotide sequence of the membrane protein (M) gene was determined from cloned cDNA. The open reading frame is preceded by a consensus transcriptional initiation sequence UCUAAACU, identical to the one found upstream of the N gene. The M gene encodes a 225-amino acid polypeptide with a molecular weight (MW) of 25,822, slightly higher than the apparent MW of 19,000-22,000 observed for the unprocessed M protein obtained after in vitro translation and immunoprecipitation. The M amino acid sequence presents a significant degree of homology (38%) with its counterpart of transmissible gastroenteritis coronavirus (TGEV). The M protein of HCV-229E is highly hydrophobic and its hydropathicity profile shows a transmembranous region composed of three major hydrophobic domains characteristic of a typical coronavirus M protein. About 10% (20 amino acids) of the HCV-229E M protein constitutes a hydrophilic and probably external portion. One N glycosylation and three potential O-glycosylation sites are found in this exposed domain. PMID- 2305556 TI - Breast cancer risk factors and screening: United States, 1987. PMID- 2305555 TI - The cauliflower mosaic virus gene III product is a non-sequence-specific DNA binding protein. AB - The interaction of the gene III product, P15, of cauliflower mosaic virus with different double-stranded DNA fragments of the viral genome was investigated. The results suggest that gene III product which showed DNA binding activity is a structural protein of the viral particle. PMID- 2305557 TI - [Etiological factors and possibilities of early diagnosis in colorectal cancer]. PMID- 2305559 TI - [Ultrasonic luminescence of blood in stomach cancer]. AB - Ultrasonic luminescence of blood plasma was studied in 428 cases of cancer, precancer and non-tumor diseases of the stomach and other viscera. The authors were the first to establish a relatively short duration of sound-luminescence of plasma in gastric cancer. Those alterations were considered indicative of neoplasm. Disease was misdiagnosed in 15.5% of cases of gastric pathology: cancer was not detected in 12.7% whereas tumor was erroneously diagnosed in 18.5% of patients with complicated gastric ulcer and other non-tumor pathology. Application of sound-luminescent method in combination with X-ray examination assured reliable diagnosis of gastric cancer in 95.1%. The method appeared instrumental in diagnosing other cancers as well. PMID- 2305558 TI - [Increase of the functional activity of natural killers under the effects of the pharmacological correction of the sympathoadrenal system state in patients with lung cancer]. AB - The influence of drugs improving sympathoadrenal system status on natural killer (NK) functional activity was studied in lung cancer patients. The activity of adenosine-metabolizing enzymes (adenosine deaminase and 5'-nucleotidase) in NK cells was found significantly altered, suggesting the involvement of this phenomenon in decreasing NK activity under tumor growth. Pharmacological correction of sympathoadrenal system status was followed by an increase in NK functional activity in lung cancer patients. PMID- 2305560 TI - [Effects of forced diuresis on butylbutanolnitrosamine induction of bladder tumors in rats]. AB - The study was concerned with the effect of forced diuresis on the frequency and morphologic pattern of bladder cancer induced with butylbutanolnitrosamine in rats. An 1.6 times increase in diuresis was followed by inhibition of bladder carcinogenesis, resulting in a 2.5-fold decrease in the tumor rate as compared to controls. The data obtained confirm the earlier suggested hypothesis of "urothelial contact" as well as epidemiologic data. PMID- 2305561 TI - [Identification of HTLV-I markers in patients with hemoblastoses]. AB - Serologic and molecular biologic techniques were used to identify association of HTLV-1 with adult T-cell leukemia/lymphoma as well as with B-cell leukemia. HTLV 1 markers (antibodies and integrated provirus) were identified in all lympho- and myeloproliferative diseases, while integrated provirus genome--in T-cell population only. PMID- 2305562 TI - [Economic bases of treatment intensification at specialized oncological facilities]. AB - The purpose of the study was to work out economic rationale for intensifying treatment at specialized oncological establishments. Modern modalities of cancer treatment require patients to be admitted to specialized hospitals. However, at present nearly half of them receive treatment in general medical establishments which, as a rule, do not have facilities for combined and complex treatment. It is estimated that shifting patient examination emphasis from hospital to outpatient clinic might increase the clinical bed turnover by 6.7% which, in turn, will allow to treat 43000 patients more in specialized hospitals every year. The introduction of such scheme will cost 6.8 times less than commission of new beds required for management of the equivalent number of cancer patients. PMID- 2305563 TI - [Errors in the diagnosis of malignant tumors during the prehospital stage]. AB - A group of experts from The P. A. Herzen Research Institute of Oncology reviewed 6000 histories of cancer. The analysis showed errors by outpatient hospital staff to account for untimely diagnosis of cancer in the majority of cases of advanced disease. A classification of medical errors was developed. Objective and subjective factors leading to errors were analysed. Review of records of diagnostic data is suggested. It is also suggested that physicians should bear responsibility for errors in oncology which have grave consequences. PMID- 2305564 TI - [Prognostic significance of metastatic involvement of regional lymph nodes in lung cancer]. AB - The study was concerned with a retrospective evaluation of the results of treatment of 1400 patients with operable epidermoid lung cancer. The prognostic significance of regional lymph node involvement in combination with such tumor parameters as site, size, degree of differentiation and gross pattern of primary tumor was evaluated. PMID- 2305565 TI - [Roentgeno-endovascular prosthetics of the superior vena cava in compression syndrome]. AB - The paper discusses the first Soviet experience of transcatheter intravascular application of endoprosthesis into superior vena cava for compression with paratracheal lymph nodes in a patient suffering Hodgkin's disease. The patient had failed to respond to 3 cycles of combination chemotherapy and 46 Gy of radiation to the mediastinum. Application of the procedure brought the vascular lumen and blood flow to normal which led to regression of compression syndrome. The self-fixing endoprosthesis dilates and forms an interior frame for the vessel thus preventing relapse of compression in case of progression of disease. PMID- 2305566 TI - [Breast cancer at present and 30 years ago]. AB - Comparison of the data on pathomorphosis of breast cancer and parameters of reproductive function of patients for 1983-1986 and 1953-1956 failed to establish increased aggressiveness of tumor during 30 years; however, the profile of factors influencing tumor development changed. At present, breast cancer is provoked by a longer and stronger estrogen stimulation; its duration has increased by 4.1 years which is an equivalent of more than 100 ovulatory cycles. PMID- 2305567 TI - [Endoscopic electrothermocoagulation of tumors in inoperable cancer of the esophagus and proximal part of the stomach]. AB - The paper discusses application of endoscopic electrothermocoagulation in complex treatment of inoperable cancer of the esophagus and the proximal part of the stomach presenting with severe dysphagia. The study included 247 such patients, with 77.3% having stage IV tumor. 202 cases underwent electrothermocoagulation as a component of the treatment modality whereas 45 received standard therapy (controls). The newly-developed procedure assured enteral nutrition in 95.4% of cases and a drop in treatment--related complication rate from 33 to 9.3%. Survival ranged 8.4-11.2 months in different study groups and was as low as 3.1 months in controls. PMID- 2305569 TI - [Use of automatic blood analyzer, Hemalog D, in cancer patients during radiotherapy and chemotherapy]. AB - The Hemalog D automatic cytochemical analyser was used to assess changes in the levels of neutrophil peroxidase and monocyte non-specific esterase in 194 cancer patients undergoing radiation and chemotherapy. Radiotherapy in the dose of 30-48 Gy did not affect functional activity of blood leukocytes. Combination chemotherapy induced moderate or severe leukopenia in 72.7% of cases. A decrease in the enzymatic activity of neutrophils and monocytes was observed in patients with normal and slightly decreased leukocyte counts. In patients with severe leukopenia, elevated levels of peroxidase and non-specific esterase in leukocytes were found. PMID- 2305568 TI - [A comparative study of immediate and long-term results of the treatment in cancer of the distal part of the stomach]. AB - Treatment results were studied in 117 cases of cancer of the distal part of the stomach; the patients had undergone subtotal resection. Postoperative lethality after Hofmeister-Finsterer's resection was 15.1%, after valve anastomosis-5.9% (overall lethality-8.3%). Postoperatively, patients with valve anastomosis did better and suffered surgery-related functional disorders less frequently than those treated after Hofmeister-Finsterer. 104 (97.2%) patients were followed up. Five-year survival was 45.2%; ten-year-32.2%. PMID- 2305570 TI - [Obstructive anuria in patients with tumors of the pelvic organs]. AB - The paper discusses the data on 57 cases of pelvic tumor--induced obstructive anuria. As a rule, obstructive anuria is easy to diagnose ultrasonography being most instrumental. Duration of anuria was found to be the main factor determining outcome in the early postoperative period. Early detection of ureteral obstruction and timely treatment prevented excretory anuria in some cases. PMID- 2305571 TI - [Differential diagnosis of secondary chondrosarcoma of the bones]. AB - A procedure based on multifactorial evaluation of the most important clinical and X-ray signs was suggested to differentiate between secondary bone chondrosarcoma and such benign lesions as chondroma and osteochondrous exostosis. The analysis included 100 patients with secondary bone chondrosarcoma and 36 of those with benign lesions. The study used complex parameters derived from two, three or four simple ones. The method described assured a 95% credibility of differential diagnosis. PMID- 2305572 TI - Occupational and environmental illness and the poison center. PMID- 2305573 TI - On rocks and hard places. PMID- 2305574 TI - Occupational illness and poison control centers. Referral patterns and service needs. AB - In a study of occupational illness reported to a regional poison control center and to gauge the center's outreach and services, we did follow-up interviews of 301 case contacts over a 6-month period. We ascertained referral routes, reasons for contacting the poison control center, and awareness of the center's function. For 122 cases a nonphysician was the initial poison control center contact. Of the nonphysician contacts, 41 had already consulted a health care provider and been referred to the poison control center for assistance. Of the 70 persons with exposure, only 21 had been aware before their exposures that poison control center services might include occupational chemical illness consultation. Physicians and nonphysicians expressed similar reasons for contacting the poison control center, with 118 of 301 identifying the need for an exposure hazard risk assessment. These data suggest that although those contacting a poison control center because of occupational illness include a variety of cases, they have many similar service needs. PMID- 2305575 TI - Academic medicine. PMID- 2305576 TI - Trust. PMID- 2305577 TI - Is it fair to blame the victim? PMID- 2305580 TI - Bernstein's hug. PMID- 2305579 TI - Fleeting moments. PMID- 2305581 TI - Progress symposium--Surgical management of chronic pancreatitis. PMID- 2305578 TI - Intracranial tuberculoma developing during therapy for tuberculous meningitis. PMID- 2305582 TI - Assessment of insertion techniques and complication rates of dual lumen central venous catheters in patients with hematological malignancies. AB - One hundred and twenty-three dual lumen silicone rubber central venous catheters were inserted into 101 patients with hematological malignancies undergoing intensive treatment. There was a perioperative complication rate of 13%. Open and closed techniques for inserting the catheter were compared. The operating time needed for introducing the catheter by the closed technique (average, 51 minutes) was significantly shorter (p less than 0.001) than the time needed for the open technique (70 minutes), whereas complication rates were equal in both techniques. On average, the catheters functioned for 149 days. Complications leading to removal were observed in 29.3% of patients, most of which were catheter-related infections (20.4%). Thromboembolic complications leading to removal were less frequent (4.1%) and appeared significantly earlier (p less than 0.001). These data indicate that introduction of the catheter by direct puncture of the subclavian vein is a quick and safe technique, and that this type of catheter is suitable for long-term use, both for infusion and for blood sampling. PMID- 2305584 TI - Pyogenic liver abscess. AB - Experience with 34 patients with pyogenic liver abscess is reviewed to evaluate the impact of percutaneous drainage and duration of antibiotic therapy on results of treatment. Patients with shock, adult respiratory distress syndrome, disseminated intravascular coagulation, jaundice, severe hypoalbuminemia, and diabetes had a poor prognosis. Percutaneous drainage was used successfully in 4 of 6 patients, but its use did not affect mortality rate or length of hospital stay. Percutaneous drainage may be the procedure of choice for selected patients. Half of our patients received antibiotics for 2 weeks or less with no abscess recurrences in this group. Long-term antibiotics may not be necessary after adequate surgical or percutaneous abscess drainage. PMID- 2305585 TI - Necrosis of intraabdominal esophagus and proximal third of the stomach after proximal gastric vagotomy and fundoplication. AB - Lesser curve necrosis is a rare but known complication of proximal gastric vagotomy (PGV). Incidence seems to increase when PGV is combined with fundoplication. In reports of this complication, the necrosis was of various sizes, but generally limited to the lesser curve. We report a 54-year-old patient with hiatus hernia, severe peptic esophagitis, and increased acid output who developed necrosis of the whole intraabdominal esophagus, cardia, and proximal third of the stomach after PGV and fundoplication with division of several short gastric vessels. A proximal gastric resection with intrathoracic esophagogastric anastomosis had to be performed. After drainage of a subphrenic abscess, the patient made a complete recovery. When combining PGV with a fundoplication, an increased risk of necrosis of the stomach must be considered. Division of the short gastric arteries should be avoided and the original Nissen fundoplication is preferred. PMID- 2305586 TI - Pancreatitis in northern Newfoundland and Labrador: a 20-year review of the Grenfell Regional Health Services experience. AB - A retrospective review of the Grenfell Regional Health Services experience with pancreatitis over a 20-year period (1968-1987) has been presented. The small number of cases in this series precludes meaningful statistical analysis, however, in general, one can state that native peoples are represented in this study in roughly the same proportion as they are represented in the population served. We have demonstrated that pancreatitis in its chronic form does occur in the Inuit of Northern Labrador. Given the prominent role that alcohol abuse plays in the social and behavioral ills of Labrador's native peoples as reflected in the high incidence of family violence, accidental deaths, and suicides, one might anticipate a disproportionately high incidence of pancreatitis and its chronic sequelae among the Inuit. The answer to this seeming paradox may be found through future study of the nature of the alcohol consumed, its pattern of consumption or of genetically-determined differences in the metabolism of alcohol and its toxic effects within the body, of differences in the composition of pancreatic secretions, or of environmental and dietary factors. PMID- 2305583 TI - Early hemodynamic changes following selective distal splenorenal shunt for portal hypertension: comparison of surgical techniques. AB - Ninety patients with cirrhosis undergoing elective distal splenorenal shunt (DSRS) for variceal bleeding between January, 1977 and September, 1988 comprised the study group. In 63 cases, the original technique of Warren was used and, in 15, the modified Britton procedure was employed. Twelve patients had a DSRS plus splenopancreatic disconnection. Thirty-four had alcoholic cirrhosis and 56 had nonalcoholic cirrhosis. Intraoperative portal pressure remained high after the shunt (29.4 cm H2O) even if its initial value was probably decreased by the loss of the splenic flow. Splenic pressure was reduced to 21 cm H2O. The hepatic artery diameter enlarged even after selective shunt (from 6.5 to 7.1 mm). The persistence of a high portal pressure allowed for the preservation of hepatopedal portal flow in 87% of cases. Disconnection between the high-pressure mesenteric area and the low-pressure splenic area seemed to be ideal in only 17% of cases. Fifty-five percent of cases had the early development of minimal or moderate portomesenteric gastrosplenic (PM-GS) collateral pathways. In 33%, the PM-GS collaterals were generally abundant and often allowed visualization of the splenic and caval veins during the venous phase of the superior mesenteric arteriograms. In this group, portal flow was generally highly reduced and even abolished. The incidence of portal thrombosis was 11%. Early angiographic checks after DSRS did not show a different hemodynamic behavior between alcoholics and nonalcoholics. Splenopancreatic disconnection seems to prevent the development of collaterals and the loss of portal perfusion after shunt surgery. PMID- 2305587 TI - Surgery for chronic pancreatitis in Zaria, Nigeria. AB - Fifteen children and 23 adults with complications of chronic pancreatitis were managed in Zaria, Nigeria from 1971 to 1987. They comprised 26 patients with chronic pseudocysts, 9 with chronic abdominal pain, and 3 with obstructive jaundice. Internal drainage was performed for 22 (85%) of the pseudocysts, with resection and external drainage, respectively, in 2 each. A longitudinal pancreaticojejunostomy was performed in a child with juvenile tropical pancreatitis syndrome and biliary bypass was performed in the jaundiced patients. The cause of chronic pancreatitis was known only in 8 (31%) of the patients. PMID- 2305588 TI - Management of chronic relapsing pancreatitis in adolescents. AB - Chronic relapsing pancreatitis in adolescence is a most uncommon clinical problem and has received minimal separate recognition in the literature. Adolescence is an age when the causes of the disease, which may operate from birth, overlap with the major etiological factors in the generality of pancreatitis in adult life. A personal series of 32 patients with pancreatitis, aged 11-20 years, is reported. Twenty-four followed a chronic relapsing course. There was, therefore, a marked reversal of the normal preponderance of acute over chronic relapsing cases. Those with underlying biliary disease, and the group in whom no etiological factors could be identified, ran an unexpectedly severe and troublesome course. This, coupled with the reversal of the acute versus chronic disease ratio, raises the question as to whether adolescent pancreatitis is a distinct subgroup in the overall spectrum of this disease. PMID- 2305589 TI - Pancreaticoduodenectomy (Whipple resection) in the treatment of chronic pancreatitis. AB - The armamentarium of the pancreatic surgeon must include multiple operative techniques, to be adapted to the clinical and anatomical findings in the patient with chronic pancreatitis. Pancreaticoduodenectomy is an essential component of this armamentarium. Its indications and limitations require continued refinement. Pancreaticoduodenectomy (Whipple operation) provides excellent results in the relief of the pain of chronic pancreatitis. The incidence of reoperation for control of pain after this procedure is less than after drainage procedures. The postoperative mortality rate in recent report is less than 2%. Whereas resection of pancreatic tissue diminishes pancreatic function, the metabolic deficits are partially compensated by the better nutritional status resulting from pain relief and discontinuation of narcotics. In experienced hands, pancreaticoduodenectomy would appear to be the procedure of choice in patients with small pancreatic ducts. In selected patients, it appears to be a good procedure and, possibly, the operation of choice when the disease is predominantly present in the head of the pancreas and/or the uncinate process, especially when strictures involve the common bile duct and duodenum. The authors prefer the procedure when a hard, chronically-inflamed mass is present in the head of the pancreas. In our experience, if the suspicion of malignancy of the head of the pancreas persists at operation, pancreaticoduodenectomy is the procedure of choice. Before undertaking resection, the individual surgeon must assess his/her own experience; a low risk is essential. The continuing alcoholic is not a candidate for pancreaticoduodenectomy. Those who will not stop drinking should seldom be accepted for resection. The same limitation exists for the narcotic addict, but few such patients are encountered today. In the authors' experience, the operation is excellent for the relief of pain. It is the lifestyle of the continuing alcoholic that poses the more significant problem. PMID- 2305590 TI - Duodenum-preserving resection of the head of the pancreas in chronic pancreatitis with inflammatory mass in the head. AB - In 141 patients with chronic pancreatitis and an inflammatory enlargement of the head of the pancreas, a duodenum-preserving resection of the head of the pancreas was performed within a 16-year period. The hospital mortality was 0.7%; the late mortality was 5%. Seventy-seven percent of the patients were completely free of abdominal pain; 67% returned to their former occupation. After a follow-up period of 3.6 years, glucose metabolism was unchanged in 81.7% of the patients, in 10.1% it deteriorated, and in 8.3% it improved permanently. In patients with severe chronic pancreatitis and an inflammatory mass in the head of the pancreas, a duodenum-preserving resection of the head of the pancreas is an alternative procedure to the Whipple operation. The surgical technique of the duodenum preserving resection includes 2 major steps: first, subtotal resection of the head of the pancreas conserving the duodenum; second, restitution of the exocrine pancreatic secretory flow from the body and tail of the pancreas by using the first jejunal loop as an interposition. In comparison to the Whipple procedure, the duodenum-preserving resection of the head of the pancreas in chronic pancreatitis spares the patient a gastric resection, a duodenectomy, and a common bile duct resection. With respect to long-lasting pain relief and preservation of the endocrine function of the pancreas, duodenum-preserving resection of the head is a highly effective surgical procedure with a low early and late morbidity and mortality due to the limited surgical resection. PMID- 2305591 TI - Group I pepsinogen for early detection of gastric cancer recurrence after total gastrectomy. AB - Group I pepsinogen (PG-I) staining was performed in the gastric carcinoma tissues of 75 patients by the peroxidase-antiperoxidase (PAP) method, 44 cases (59%) of which were positive for PG-I, suggesting that they were PG-I-producing gastric carcinomas. Type IV gastric carcinoma by the Borrmann classification and/or poorly-differentiated adenocarcinoma were positive for PG-I in high incidence. Serum and urinary levels of PG-I were determined by the Pepsinogen I Radioimmunoassay Kit in patients with gastric carcinoma who underwent total gastrectomy. The levels of PG-I declined remarkably or disappeared at 1 week after curative surgery. Changes of serum PG-I levels after total gastrectomy were observed in 9 patients with PG-I-producing gastric carcinomas, 7 of whom died of recurrence. The PG-I values became elevated with recurrence in 5 of them and the values increased with the passage of time. In contrast, no substantial changes in PG-I levels occurred in patients with no recurrence. These results suggest that PG-I is useful for the early detection of recurrent disease after total gastrectomy in patients with PG-I-producing gastric carcinomas. PMID- 2305592 TI - Taking up the cudgels: cigarettes, cancer and car keys. PMID- 2305593 TI - Medicine abroad: I. Hospital #3 in Leningrad. PMID- 2305594 TI - Medicine abroad: II. Glastnost in Moscow, Tbilisi, Baku. PMID- 2305595 TI - Access: will we nibble at the edges or bite the bullet? PMID- 2305596 TI - Eosinophilia, myalgia associated with L-tryptophan use: case report. PMID- 2305598 TI - [The dream of Irma's injection. Theme polyphony and problem solving]. AB - This paper on the specimen dream of psychoanalysis presents in its first part a survey of the manifold interpretive themes that have been found in this complex dream. Apart from wish fulfillment attributed to its content by Freud himself, this dream contains themes of the dreamer's creativity and points out the developmental state of psychoanalysis existing at that time. It gives a rather accurate picture of Freud's knowledge on transference and countertransference in 1895 and informs us on a series of psychological problems of the dreamer himself: his feelings of guilt, his latent homosexual tendencies, his aggressiveness toward colleagues and women as well as the state of his marital relation. A problem solving interpretation of the Irma dream reveals the still defective state of his new healing method as illustrated by the many therapeutic errors committed in the therapy of his patient Irma. The polyphony of themes that can be seen in the initial dream of psychoanalysis warns of monothematic interpretive proposals by therapists that are likely to be ill-understood or frankly rejected by patients in favor of openended interpretations. PMID- 2305597 TI - [A 20-year follow-up study of a sample of 50 pairs of twins with neurotic psychosomatic disorders]. AB - As part of a research project, examination was made of a sample of 50 pairs of twins (21 pairs of identical twins, 16 pairs of non-identical twins of the same sex, and 13 pairs of male-female twins [n = 100 test persons]) between 1963 and 1969 and again recently after a period of 20 years. The index twins were drawn from among the patients who made use of the services of an out-patient psychotherapeutic clinic, and they were determined to be either psychoneurotic, character neurotic, or psychosomatically ill. The question examined was again one of nature vs. nurture. Identical twins showed a significantly higher similarity with regard to the seriousness of their neuroses and the manifestation of neurotic symptoms than did non-identical twins. Noticeable similarities existed in cases of depressive disturbances, disturbances of oral and aggressive behavior, and disturbances of interpersonal contact. With regard to the influence of variables in the environment, we examined the effect of factors in early childhood on neurotic development. Lack of a reference person, a negative attitude on the part of parents toward the child, etc., frustration within and outside the family have an effect on the manifestation of neuroses and on the course of their development. The influence of early childhood factors on the degree of neurotic disorder is still to be noted in the current point prevalence. PMID- 2305599 TI - [Primary and secondary process thinking in normal probands, neurotic and borderline patients]. AB - In the present paper normals, neurotics and borderline patients were compared with respect to primary and secondary process thinking. The Holtzman Inkblot Technique was used to assess the different modes of functioning. As it was expected, normals had more indicators of the most severe levels of primary process thinking than neurotics, but less than borderline patients. On the other hand it could be demonstrated that in normals the reality testing ability and synthetic functioning were not impaired compared to neurotics. In the contrary, the normals exceeded the neurotics concerning indicators of abstractive abilities. The results are discussed with regard to the hypothesis of a continuum of normal and deviant thinking and with regard to the concept of adaptive regression in the service of the ego. PMID- 2305600 TI - [Change in conflict management in inpatient psychotherapy. A psychometric study of defense behavior]. AB - A recently developed questionnaire for measuring various mechanisms of defence was given to a consecutive sample of 54 patients at the beginning and the end of their psychotherapy on our psychosomatic ward. A significant reduction was ascertained on the dimensions principalization--or intellectualization--and turning against self, a significant increase on the dimension turning against object. The results of this assessment can be interpreted in the sense of a more adequate coping with conflicts which has to be proved by further investigations. PMID- 2305601 TI - In vitro modulation of porcine Leydig cell steroidogenesis by phorbol-12 myristate-13-acetate and 1,2-dioctanoylglycerol. AB - Serum-free primary cultures of neonatal (1-day-old) porcine Leydig cells were used to study the effects of phorbol-12-myristate-13-acetate and 1,2 dioctanoylglycerol on testosterone and pregnenolone production. Phorbol-12 myristate-13-acetate alone from 0.001-10 mumol/l stimulated testosterone and pregnenolone production, whereas 1,2-dioctanoylglycerol alone had no effect on steroid production, relative to control. Phorbol-12-myristate-13-acetate and 1,2 dioctanoylglycerol each inhibited pLH-stimulated testosterone and pregnenolone production. To further clarify the influence of these protein kinase C activators on steroidogenesis, cultured Leydig cells were treated with either phorbol-12 myristate-13-acetate or 1,2-dioctanoylglycerol plus forskolin (an adenylate cyclase activator). Both phorbol-12-myristate-13-acetate and 1,2 dioctanoylglycerol inhibited forskolin-stimulated testosterone production. Phorbol-12-myristate-13-acetate had no effect on forskolin-stimulated pregnenolone production and only the highest concentration of 1,2 dioctanoylglycerol (100 mumol/l) inhibited forskolin-stimulated production of pregnenolone. These data demonstrate that porcine Leydig cell steroidogenesis can be modulated by interactions of the protein kinase C and protein kinase A second messenger systems. PMID- 2305602 TI - Effect of adrenalectomy at different pregnancy stages on maternal and fetal serum corticosteroid binding globulin and corticosterone in the rat. AB - The response of pregnant rat corticosteroid binding globulin to maternal adrenalectomy was studied as a function of the stage of pregnancy. Non-pregnant or pregnant rats were deprived of their adrenal glands during 4 days. In non pregnant animals, adrenalectomy led to undetectable corticosterone levels and to the doubling of corticosteroid binding globulin. In pregnant rats adrenalectomized at 12 days and studied at 16 days, the serum corticosterone was likewise undetectable and the corticosteroid binding globulin was doubled as compared with pregnant rats of the corresponding age. In contrast, adrenalectomy from day 14 to 18 or from day 16 to 20 did not deplete the maternal serum corticosterone and the corticosteroid binding globulin remained unchanged. Under these conditions neither fetal corticosteroid binding globulin nor fetal corticosterone were modified. However, when the pregnant rats adrenalectomized from day 16 to 20 also received an injection of 30 mg of metyrapone on days 19 and 20 in order to inhibit fetal adrenal secretion, the maternal response was again a depletion of serum corticosterone together with an increase in corticosteroid binding globulin. Under these conditions, the fetus also reacted by a fall of corticosterone and a rise of corticosteroid binding globulin. Our results suggest that the maternal response of corticosteroid binding globulin to adrenalectomy depends on the pregnancy stage inasmuch as it may be influenced by a supply of corticosterone from the fetus during late pregnancy. Moreover, they show that in this late period, fetal corticosteroid binding globulin is regulated independently. PMID- 2305603 TI - Ciamexone in endocrine orbitopathy. A randomized double-blind, placebo-controlled study. AB - The influence of ciamexone on the activity and course of endocrine orbitopathy was investigated. Fifty-one patients with active orbitopathy classes II-VI were allocated randomly to two groups: over a period of six months, 26 patients received 300 mg/day ciamexone and 25 patients received placebo tablets. In both groups, prednisolone was administered in addition in the first four weeks. Ophthalmological investigations and clinical tests as well as orbit sonography were carried out before as well as one, three and six months after the beginning of therapy. Before and after treatment, computer tomography of the orbit was performed. Symptoms and signs did not show any significant improvement one and six months after therapy. No differences between the two therapy groups were observed. Detailed examination did not reveal any preferential action of the product on individual parameters. Sonography and computer tomography showed no significant alterations of the thickness of the oculomotor muscles. Thus administration of 300 mg ciamexone once a day as compared with placebo did not show any effect on the course and activity of endocrine orbitopathy. PMID- 2305604 TI - Progesterone regulation of prolactin release from human endometrial stromal cells in culture: potential bioassay for progestational activity. AB - Prolactin was produced by endometrial stromal cells, but not by epithelial cells, in primary culture. Production was stimulated by progesterone in a time and dose (1-1000 nmol/l) dependent way. Stimulation was started one day after plating. The release of prolactin started one day earlier in cultures from luteal phase than proliferative phase endometria. The responsiveness to progesterone declined with time in culture, sooner in luteal than in proliferative phase cultures, but could, at least partly, be maintained by including estradiol (10 nmol/l) in the medium. Lost response to progesterone could be restored by stimulation with estradiol for two days. The results indicate that prolactin synthesis in the endometrium is regulated directly by progesterone, and indirectly by estradiol. We suggest that prolactin production in primary stromal cell cultures could serve as a bioassay for progestational activity of steroid hormones in the human endometrium. PMID- 2305605 TI - The prolactin releasing effect of histamine is unrelated to its vascular action. AB - We investigated in male rats whether the prolactin releasing effect of systemically infused histamine might be attributed to a vasodilatatory action of the compound. Intraarterial infusion of histamine (3.8 mumol) over 1 min increased the plasma PRL 10-fold. This effect was prevented by prior ia infusion of the H1 receptor antagonist mepyramine and slightly augmented by prior ia infusion of the H2 receptor antagonist cimetidine. At the same time histamine caused an immediate 38% decrease in mean arterial blood pressure, which remained 15% below the initial level during the rest of the 60-min observation period. The depressor effect of histamine was prevented by pretreatment with mepyramine and partly prevented for the first 5 min by pretreatment with cimetidine. Since the H1 receptor seemed to be the predominant mediator of the histamine-induced hypotension and PRL release, a causative interaction is possible. However, when the histamine-induced decrease in blood pressure was prevented by simultaneous iv loading with saline the PRL response to histamine was still evident. Furthermore, when the histamine-induced decrease in blood pressure was mimicked by ia infusion of the vasodilator nitroprusside no effect was observed on PRL secretion. We conclude that the histamine-induced stimulation of PRL secretion is independent of the profound depressor action of the amine. PMID- 2305606 TI - Effects of central osmotic stimulation on vasopressin and enkephalin release into the blood and cerebrospinal fluid and blood pressure. AB - To assess the central effect of hypertonic NaCl on the release of vasopressin (AVP) and methionine enkephalin-like substances into the blood and cerebrospinal fluid, and on blood pressure, ventriculocisternal perfusion (0.25 ml/min, 60 min) was performed in anesthetized dogs with artificial cerebrospinal fluid (CSF), either isotonic (300 mosmol/kg) or hypertonic (600 and 1200 mosmol/kg). The effect of central administration of a V1-AVP antagonist on the central osmotic challenge was also studied. In dogs, given 600 mosmol/kg, CSF osmolality increased with a concomitant rise in mean arterial pressure and plasma AVP concentrations. Plasma osmolality, heart rate, CSF AVP and plasma and CSF methionine enkephalin-like substances showed no significant change. In dogs, given 1200 mosmol/kg, the CSF osmolality increase was accompanied by a rise in mean arterial pressure, heart rate, plasma AVP and CSF AVP. Plasma osmolality and plasma and CSF methionine-enkephalin-like substances did not change significantly. A V1-AVP antagonist given centrally attenuated the rise in mean arterial pressure induced by osmotic challenge. In dogs, given 300 mosmol/kg, no parameters changed significantly except for a gradual fall in heart rate. These results suggest that central osmotic stimulation by hypertonic NaCl increases blood pressure, heart rate and the release of AVP, but not methionine enkephalin like substances, into the blood and CSF, and a V1-blocker given centrally attenuates the pressor response. PMID- 2305607 TI - Episodic nyctohemeral secretion of melatonin in adult humans: lack of relation with LH pulsatile pattern. AB - The concentration of melatonin and LH were determined in plasma samples obtained at 10-min intervals during 4 h of darkness (00.00-04.00 h) from 4 normal women, age 23-27 years, in the early follicular phase of the menstrual cycle and in 6 normal men, age 23-31 years. Additionally, melatonin concentration was determined in samples obtained from the men at 10-min intervals for 4 h during the day (10.00-14.00 h). A pulsatile pattern of melatonin secretion was found for all the subjects during darkness. There was no significant difference between women and men as to the number of pulses (2.8 +/- 0.5 vs 5.2 +/- 1.0 per h), amplitude of pulses (51.3 +/- 28 vs 27.2 +/- 6 ng/l), concentration per 4 h (32.5 +/- 13 vs 31.0 +/- 5 ng/l), or apparent half-life of melatonin (19.3 +/- 2.3 vs 15.3 +/- 7.5 min). The mean amplitude of the melatonin pulse correlated (r = 0.863, p less than 0.001) with the mean melatonin concentration per 4 h. A pulsatile LH secretion pattern was found for the 10 subjects and did not correlate significantly with the melatonin secretion pattern. The results are consistent with an independent signal for the demonstrated nyctohemeral pulsatile melatonin and LH secretions. PMID- 2305608 TI - Azathioprine in the treatment of thyroid-associated ophthalmopathy. AB - Azathioprine is used in the treatment of thyroid-associated ophthalmopathy, but its effectiveness has not been evaluated. In the present study 20 patients with moderately severe ophthalmopathy were recruited; 10 patients received azathioprine and the other 10 matched patients served as controls. During the treatment period (lasting 1 year) and 1 year later, no changes were detected in exophthalmometer readings, visual acuity or measurement of palpebral aperture. Differential intraocular pressure fell with time in both groups. Azathioprine treatment did not significantly influence these parameters, although it did induce significant decrease in thyroid microsomal antibodies and in thyroid stimulating hormone binding inhibiting immunoglobulin index. The study demonstrates that thyroid-associated ophthalmopathy of moderate severity, often improves with time without treatment. Azathioprine is not an effective treatment for patients with moderately severe thyroid-associated ophthalmopathy. The study emphasises the necessity for an adequately matched control population in the evaluation of therapy. PMID- 2305609 TI - Plasma level changes of fentanyl and midazolam after release of a prolonged thigh tourniquet. AB - In 14 elderly orthopedic patients undergoing total knee joint replacement, the influence of complete arterial occlusion of the limb on the course of plasma levels of fentanyl and midazolam was examined. The patients were premedicated with midazolam intramuscularly (0.05 mg/kg) and were then given neurolept anesthesia in dosages of 0.1 mg/kg midazolam and 0.01 mg/kg fentanyl intravenously prior to the placement of the tourniquet. Up to 4 h after the tourniquet was released, plasma levels of fentanyl and midazolam as well as pH value, PaCO2 and plasma lactate levels were measured. In 12 patients there was an increase in fentanyl and in 10 patients an increase in midazolam plasma levels after tourniquet release. The maximum increase varied between 1 min and 2 h after release. The plasma levels of midazolam after removal of the tourniquet varied greatly between individuals. Especially patients older than 70 years showed excessively high concentrations of midazolam. These results would indicate that there can be a clinically significant increase of fentanyl and midazolam levels due to initial reperfusion of the lower extremity following prolonged ischemia. Therefore a correspondingly extended period of postoperative surveillance is advisable. PMID- 2305611 TI - Calcium accumulation by sarcoplasmic reticulum in whole muscle homogenate preparations of malignant hyperthermia diagnostic patients and pigs. AB - Calcium accumulation by the sarcoplasmic reticulum in whole muscle homogenate preparations of malignant hyperthermia-susceptible (MH+) and non-susceptible (MH ) humans and pigs was investigated using a calcium electrode at 35 degrees C. Sarcoplasmic reticulum of MH+ humans and pigs showed normal Ca2+ accumulation, with no difference being observed in the rate and the time taken to achieve maximal accumulation. However, the capacity for Ca2+ accumulation by the sarcoplasmic reticulum in MH+ humans and pigs is considerably less stable than normal after prolonged ageing of the whole muscle homogenate preparations in ice. In MH+ patients, the capacity for Ca2+ accumulation by the sarcoplasmic reticulum showed a decline of 62% at 22 h ageing and 70% at 48 h ageing, as compared with a reduction of only 23% in MH- patients. In MH+ pigs, the sarcoplasmic reticulum showed a 96% deterioration in the capacity for Ca2+ accumulation as compared with a loss of only 40% in MH- pigs at 7 h ageing in ice. In both humans and pigs, the decline in Ca2+ accumulation was prevented by incubating the whole muscle homogenate preparations for 2 h at 35 degrees C prior to ageing the preparations. The diminished Ca2+ accumulating capacity of the sarcoplasmic reticulum in whole muscle homogenate preparations of MH-susceptible individuals in our experimental protocol provides a potential diagnostic test for malignant hyperthermia susceptibility. PMID- 2305610 TI - A comparison of glucose-free 2% lidocaine and hyperbaric 5% lidocaine for spinal anaesthesia. AB - Fifty patients scheduled to undergo transurethral surgery of the bladder were allocated to receive spinal anaesthesia with either glucose-free 2% lidocaine (80 mg) or hyperbaric 5% lidocaine (80 mg). Onset time, cephalad spread of analgesia, duration of analgesia, duration and intensity of motor block, quality of analgesia, and the patients' ability to walk 5 m and to micturate postoperatively were assessed. Onset and spread of analgesia were fast and comparable in the two groups. At 60 min, the median segmental level of analgesia was T9 and T10 for the 2% and the 5% group, respectively, allowing transurethral surgery to be performed for at least 1 h. In the 2% group the motor block was more pronounced and longer lasting than in the 5% group. Two patients in the 5% group needed general anaesthesia because of pain. The time from injection of the spinal anaesthetic until the patients were able to walk 5 m and to micturate was equal in the two groups, and 89% of all the patients were able to walk and micturate within 4 h. It is concluded that spinal anaesthesia with 80 mg and 2% or 5% lidocaine provides analgesia for transurethral surgery and is characterized by fast recovery of motor and detrusor function. PMID- 2305612 TI - Disturbances of blood-flow velocity in the dorsal veins of the hand after vein cannulation and cannula fixation in the anaesthetised patient. AB - Modifications of the mean blood-flow velocity in the dorsal veins of the hand were assessed semi-quantitatively with continuous wave (CW) Doppler equipment in 32 anaesthetised patients (17 men and 15 women), 23-78 (median = 56) years of age, before and after venous catheterisation with cannula fixation to the skin. Cannulation of the vein caused a 48% reduction in the mean blood-flow velocity and made it impossible to detect any flow with the equipment used in 22% of the patients. A 10% further reduction in the mean blood-flow velocity and in the number of subjects with undetectable blood flow was observed after fixation of the cannulae. Age, small vein diameter, and hyperventilation (end-tidal carbon dioxide less than or equal to 3.5 volume % appeared to be significant factors reducing blood-flow velocities in the cannulated veins. It is concluded that venous catheterisation and fixation of the cannula induce a significant reduction in the blood-flow velocity. PMID- 2305613 TI - Neuromuscular effects of isoflurane in patients with myasthenia gravis. AB - Seventeen myasthenia gravis and seven control patients were studied mechano (MMG) and electromyographically (EMG) during isoflurane/oxygen/air anaesthesia. In myasthenic patients the mean train-of-four ratio and neuromuscular block (by MMG) during 1.9 MAC isoflurane anaesthesia were 55 +/- 9% and 46 +/- 12%, respectively. The correlation between simultaneous MMG and EMG measurements was excellent (r2 = 0.933, P less than 0.001). The occurrence of HLA-B8 together with acetylcholine receptor antibodies seems to predispose myasthenic patients to a neuromuscular depression produced by isoflurane. Our current and prior results show that isoflurane possesses approximately twice as strong a neuromuscular blocking effect as halothane in myasthenic patients. PMID- 2305614 TI - Correlation between EEG and heart rate variation in deep enflurane anaesthesia. AB - Variations in heart rate during deep enflurane anaesthesia were studied in 11 women admitted for elective surgery. Correlation was found between heart rate variations and bursts and suppressions in the EEG patterns. The onset of bursts coincided with accelerating heart rate, and the onset of suppressions was combined with a fall in heart rate in all patients. The correlation is not explained by ventilation arrhythmia. Both the cortical electrical activity and heart rate fluctuation are probably controlled by the same subcortical factor. PMID- 2305615 TI - A prospective study of risk factors and cardiopulmonary complications associated with anaesthesia and surgery: risk indicators of cardiopulmonary morbidity. AB - The aims of this study were: 1) to describe the frequency and type of cardiopulmonary complications, 2) to identify factors significantly associated with cardiovascular and pulmonary complications associated with anaesthesia and surgery, and 3) to estimate the total risk of cardiopulmonary complications for an anaesthetic when a combination of risk factors is present. Seven thousand three hundred and six anaesthetized patients undergoing gastrointestinal, urological, gynaecological, and orthopaedic surgery were included in the study; 6.3% (1:16) had one or more cardiovascular complications requiring intervention associated with anaesthesia and surgery, and 4.8% (1:21) had pulmonary complications. The total incidence of patients with one or more complications associated with anaesthesia and surgery was 9.4% (1:11). Based on logistic regression analyses, our data indicate that the following patient categories constitute high risk patients with regard to cardiovascular complications: patients aged greater than or equal to 70 years, patients with a history of ischaemic heart disease (IHD) with previous myocardial infarction less than 1 year, a history of chronic heart failure (CHF), and in patients admitted to major surgery. The extent of pulmonary complications following anaesthesia and surgery was significantly correlated to patients aged greater than or equal to 70 years, preoperative chronic obstructive lung disease (COLD), major surgery, and to general anaesthesia involving muscle relaxants. Attempts to estimate the cardiopulmonary complications which may accompany anaesthesia and surgery provided important information about the anaesthetic course and outcome. With our model it seems possible to distinguish between very different levels of cardiopulmonary risk in the anaesthetic patient. PMID- 2305616 TI - Treatment of pancreatic pain with interpleural bupivacaine: an open trial. AB - This study comprised 12 patients admitted for interpleural catheter treatment of chronic pancreatic pain. After the insertion of a left-sided interpleural catheter, 20 ml of bupivacaine 0.5% plain was given, followed by top-ups of 10-20 ml bupivacaine 0.5% as needed. Catheters were left in situ for 12-30 h. Immediate pain relief was achieved in all patients. Five patients had only a single blockade offering pain relief for a median of 33 days. One patient suffering from pancreatic carcinoma remained pain-free until death 45 days later. Seven patients returned for a second blockade after a median of 10 days. After this second blockade long-lasting pain relief was achieved in three patients for 70, 105 and 145 days. Two patients experienced pain relief lasting 11-14 days, while in two patients only a short-lived effect was observed, 3-8 days. Unimportant pneumothorax occurred in one patient. No cardiovascular or respiratory side effects were recorded. We consider interpleural blockade an alternative worth further investigations in the future in the treatment of patients suffering from chronic pancreatic pain. PMID- 2305617 TI - Measurement of cardiac output by the thermodilution method during left thoracotomy in the lateral position in the dog. AB - The validity of cardiac output measurement by thermodilution in the lateral position during thoracotomy was assessed. Three balloon thermodilution Swan-Ganz catheters were placed in the pulmonary artery trunk and the right and left pulmonary arteries in 12 mongrel dogs, after left thoracotomy had been performed. Cardiac output was measured simultaneously from two of the three sites. The cardiac output measurements show no significant difference related to the location of the catheter extremities: the mean cardiac index was found to be 2.164 +/- 0.448 l/min/m2 from the pulmonary artery trunk, 2.127 +/- 0.404 l/min/m2 from the left branch and 2.116 +/- 0.421 l/min/m2 from the right branch. It is concluded that the measurement of cardiac output during left thoracotomy is valid, whether the thermistor is situated in the pulmonary artery trunk or in a main branch to either the dependent or non-dependent lung. PMID- 2305618 TI - Prilocaine-induced methemoglobinemia evidenced by pulse oximetry. AB - Methemoglobinemia was suspected in a healthy 19-year-old woman, when the pulse oximeter reading (SpO2) was 88% after a plexus brachialis block with 550 mg (35 ml, 1.5%) prilocaine. The patient was receiving 50% oxygen, and the PaO2 was 48.6 kPa (365 mmHg). After start of methylene blue treatment, with a total dose of 1 mg/kg, the SpO2 showed a gradual increase. This case report emphasises the potential advantage of arterial oxygen saturation monitoring with a pulse oximeter, but also the importance of the correct interpretation of the SpO2 reading. PMID- 2305619 TI - Bradycardia as a side-effect to oxybuprocaine. AB - Sinus bradycardia was observed as a side-effect to the use of 0.4% oxybuprocaine eye-drops in a 48-year-old man with acute conjunctivitis. Blood pressure was not measurable during the episode. PMID- 2305620 TI - Spondylitis without epidural abscess formation following short-term use of an epidural catheter. AB - A 42-year-old patient had undergone total hip replacement for aseptic femoral head necrosis 9 years previously. He now presented with loosening of the prosthesis and pseudoarthrosis sustained following a femoral shaft fracture 7 months earlier. A total hip replacement was carried out in general anaesthesia combined with an epidural catheter. The epidural catheter was removed on the third postoperative day, after which the patient complained of persistent lumbar pain which was associated with meningismus, fever, leucocytosis and a raised erythrocyte sedimentation rate. In spite of intensive laboratory and radiological investigation, 15 weeks elapsed before a radiological diagnosis of spondylitis of L1 and L2 could be made. Aspiration biopsy of the L1/L2 disc space yielded a growth of Pseudomonas aeruginosa. Antibiotic therapy was begun immediately but could not prevent spread of infection to the adjacent disc-space T12/L1 and the vertebral body T12. The patient made a slow recovery and was discharged in a satisfactory condition wearing a lumbar brace some 9 months after the operation. No evidence of epidural abscess formation was found at any stage and no direct connection between the use of the epidural catheter and spondylitis could be established. PMID- 2305621 TI - Uteroplacental blood flow measured by placental scintigraphy during epidural anaesthesia for caesarean section. AB - The uteroplacental blood flow was measured before and during epidural anaesthesia for caesarean section in 11 women. The blood flow was measured with dynamic placental scintigraphy. After an i.v. injection of indium-113m chloride, the gamma radiation over the placenta was recorded with a computer-linked scintillation camera. The uteroplacental blood flow could be calculated from the isotope accumulation curve. The anaesthesia was performed with bupivacaine plain 0.5%, 18-22 ml and a preload of a balanced electrolyte solution 10 ml/kg b.w. was given. The placental blood flow decreased in eight patients and increased in three with a median change of -21%, not being statistically significant. No correlation between maternal blood pressure and placental blood flow was found. PMID- 2305622 TI - The effect on uteroplacental blood flow of epidural anaesthesia containing adrenaline for caesarean section. AB - The effect on uteroplacental blood flow of an epidural anaesthesia containing adrenaline for caesarean section was investigated in ten healthy women using dynamic placental scintigraphy with indium-113m and a computer-linked gamma camera. The epidural anaesthesia was performed with 18-22 ml bupivacaine 5 mg/ml with adrenaline 2.5 micrograms/ml followed by an i.v. balanced electrolyte infusion of 10 ml/kg b.w. A significant median decrease in the total maternal placental blood flow of 34% was found (P less than 0.01). There was also a significant decrease in maternal mean blood pressure of 3 mmHg (0.4 kPa) (P less than 0.05) and a significant negative correlation between the change in maternal blood pressure and the change in uteroplacental blood flow (r = -0.69, P less than 0.05). PMID- 2305623 TI - Ventilatory effects of almitrine bismesilate in dogs breathing normoxic, hyperoxic and hypoxic mixtures. AB - The ventilatory effects of 1 mg.kg-1 i.v. almitrine were studied in five dogs anaesthetized with halothane 2% under conditions of normoxia, hyperoxia and hypoxia. Ventilation (minute ventilation, respiratory frequency, tidal volume, duration of inspiration and expiration, ratio TI/Ttot and VT/TI), Pao2, Paco2, pHa, systemic arterial pressure and heart rate were measured in air before and following almitrine; in air, after inhalation of pure oxygen and after almitrine in hyperoxia; in air, during hypoxia with Fio2 progressively decreased from 0.21 to 0.12 and after almitrine in hypoxia (FIO2 = 0.12). Halothane decreased ventilatory response to hypoxia. Almitrine stimulated ventilation irrespective of the level of oxygenation and restored the ventilatory response to hypoxia. Hyperoxia did not suppress ventilatory action of almitrine whose action is probably partly central. Hypoxia and almitrine did not induce major systemic haemodynamic modification. PMID- 2305624 TI - Observations on intracranial dynamics during respiratory physiotherapy in unconscious neurosurgical patients. AB - The effects of airway care procedures on intracranial dynamics were studied in 12 patients with intracranial lesions. The patients had controlled ventilation and were treated according to a standardized protocol with endotracheal suction and bag squeezing. Intracranial, arterial blood and airway pressures were recorded and cerebral perfusion pressure was calculated. Both methods used for airway care elicited marked changes in intracranial, arterial blood and cerebral perfusion pressures during the treatment session. However, within 1 min after termination of the procedure the different pressure levels returned to pretreatment values except for the intracranial and arterial blood pressure in endotracheal suction. Cerebral perfusion pressure, calculated at different time intervals: 1, 5 and 15 min after the treatment, showed only minor deviations from values before treatment. The mean values varied from 70 to 90 mmHg (9.3 to 12.0 kPa) and the lower limit of the 99% confidence interval of the means was never below 55 mmHg (7.3 kPa). At times complementary administration of sedatives during endotracheal suction was found to induce a drop in arterial blood pressure and cerebral perfusion pressure. In conclusion, patients with severe brain injuries treated on mechanical ventilation are exposed to equal risks when using bag squeezing for airway care as when using traditional endotracheal suction. Regardless of the method used, patients should be adequately sedated before starting the procedure in order to reduce the risk of adverse effects. PMID- 2305625 TI - Effects of easily chewable diet and unilateral extraction of upper molars on the masseter muscle in developing mice. AB - The effects of easily chewable diets and unilateral extraction of upper molars on the masseter muscle were studied in developing mice. A liquid diet requiring no mastication suppressed the development of the masseter muscles more than a fine grained diet, and extraction of unilateral upper molars also caused inhibition of muscle development. Moreover, both unilateral extraction of upper molars and a liquid diet had an additive effect on the suppression of the postnatal development of the masseter muscle, and bilateral suppression of the development of the masseter muscle was induced following unilateral extraction of upper molars. These findings suggest that the sensory input from the sensory endings in the periodontal ligament may also play an important role in the postnatal development of the masseter muscle and that there may be some crossing pathways to convey the sensory input coming from the side of the extracted upper molars to the contralateral motor neurons via the interneuronal circuits. PMID- 2305627 TI - Eccrine sweat glands of rat fingertips. Scanning electron microscope observations after enzymatic digestion of dermal connective tissue. AB - By removing epidermis with EDTA and a subsequent enzymatic digestion of dermis, eccrine sweat glands of rat fingertips were exposed and examined by scanning electron microscopy (SEM). Different protocols were tested to remove as much connective tissue as possible, while minimizing damage to other structures, and to expose the epithelial surface of secretory tubules in order to display vascular and nervous networks. SEM observations gave detailed information on the relationship between epithelial secretory cells and myoepithelial cells, as well as on the vascular and nervous networks which surround the glomeruli of glands. PMID- 2305626 TI - Chronological and structural disorder of the spindle-shaped body during human spermatid differentiation. AB - In a testicular biopsy of an infertile man, most of the spermatids revealed a lack of the middle piece because of a malformed or untimely occurring spindle shaped body. When during spermatid differentiation the spindle-shaped body appeared, it contained the typical bundles of tubules but was often reduced in size and arranged only unilaterally to the axoneme. After the disappearance of the incomplete spindle-shaped body, the annulus did not descend, the ribs of the fibrous sheath of the principal piece were found far proximally and the mitochondrial sheath of the middle piece could not be formed. In consequence of this faulty development, the spermatozoa were immotile. PMID- 2305628 TI - Vasopressinergic axon collaterals and axon terminals in the magnocellular neurosecretory nuclei of the rat hypothalamus. AB - Axon collaterals emerging from the vasopressinergic neurons of the supraoptic (SON) and paraventricular (PVN) nuclei and recurving back towards their respective nuclei have been previously reported. Since such axon collaterals can play a role in the neuromodulation of SON and PVN, these nuclei have been further investigated immunohistochemically under the light and electron microscope. The PAP technique, using a commercial antibody, was employed. Vasopressin-positive axon collaterals were seen to recurve towards their nuclei of origin. In the latter, vasopressinergic intrinsic neurons were also observed. Under the electron microscope, axon terminals containing vasopressin-immunoreactive neurosecretory granules were noted. Such terminals presumably arise from the vasopressin positive recurrent axon collaterals or from the intrinsic neurons for the purpose of neuromodulation within the SON and PVN. PMID- 2305629 TI - Day-night differences in the vesicle populations of nerve terminals in the rat and chick pineal gland. AB - Day-night differences in the ultrastructure of pineal neuronal elements were quantitated in the rat and the chick--two species that exhibit important differences in adrenergic control of melatonin synthesis. Area densities of small clear vesicles (40-60 nm) and small dense-cored vesicles (40-60 nm) in nerve terminals were significantly reduced during the night in the rat. In the chick, there were no day-night differences in the frequency of clear vesicles, but the number of small dense-cored vesicles tended to be greater at night. There was no effect of day-night sampling on area densities of large dense-cored vesicles (80 120 nm) in either species. These findings are consistent with biochemical evidence for day-night species differences in the adrenergic control of pineal function. PMID- 2305630 TI - Electron-microscopic studies on the pathogenesis of exencephaly and cranioschisis induced in the rat after neural tube closure: role of the neuroepithelium and choroid plexus. AB - Exencephaly was induced in Wistar rat fetuses by the administration of a single dose of cyclophosphamide (15 mg/kg) in saline, after neural tube closure. The neuroepithelium (NE) and the choroid plexus were studied electron-microscopically in sections taken from a few hours after treatment to day 19 of gestation. The reduction in polyribosomes and condensation of the nucleus and cytoplasm were followed by cell death and fragmentation in the NE. Such cellular debris were phagocytosed and digested by the apparently normal neuroblasts. Cell proliferation was inhibited. The progressive loss of cells and lack of neuropil arborisation resulted in the expansion of the extracellular space and reduced intercellular contacts. The internal and external limiting membranes became weak. The vascular endothelium was attenuated. There were no obvious discontinuities of endothelium, but clusters of extravascular red blood cells, particularly in the vicinity of capillaries, in the cavitations in the NE and in the ventricular lumen were prominent by day 15. Subsequently, the cavities in the NE frankly communicated with the ventricle internally and subcutaneous blebs externally. The choroid plexus of exencephalic embryos was more extensive than that of the age matched controls. Hydropic vacuoles, dense bodies, distended mitochondria, clusters of vesicles in basal cytoplasm and lakes of monoparticulate glycogen progressively increased in the plexus cells. Pericapillary oedema was obvious in the core of the plexus. These observations suggest that, in addition to cell death and reduced cell proliferation, haemorrhage, oedema and enhanced cerebrospinal fluid production contribute to reopening of the closed neural tube in this model. PMID- 2305631 TI - Implantation of fetal thymus and sympathetic ganglion within the anterior eye chamber in mice, to study neuro-immune interaction in thymic development. AB - In this study 13- to 14-day fetal thymic lobes were implanted within the anterior eye chambers in mice either with or without a syngeneic newborn sympathetic ganglion. It was observed after 6 weeks of implantation that the thymic lobes that grew with the ganglia had fewer lymphoid cells than their counterparts which were grown without the ganglia. The cells that developed within the thymic lobes were Thy-1- and peanut agglutinin-positive. The thymic lobes that grew with sympathetic ganglia also showed the presence of adrenergic nerves, perhaps due to reinnervation of the thymic grafts from the ganglia. PMID- 2305632 TI - Development of the fetal mouse palate in suspension organ culture. AB - Explanted palates of day 12 and day 13 mouse fetuses were cultured in a chemically defined serumless medium for 48-72 h by a suspension culture technique. The palate of day 12 fetuses closed successfully within 72 h and that of day 13 fetuses within 48 h. Both macroscopically and histologically, the in vitro fusion of palatal shelves simulated the palatogenetic process in vivo. This novel technique for culturing the fetal mouse palate may be of potential use for the study of palatogenesis and in developmental toxicology. PMID- 2305633 TI - Morphometry and elemental analysis of rat exocrine pancreas following administration of trypsin inhibitor. AB - The morphological responses of the exocrine pancreas of the adult male rat to soybean trypsin inhibitor (STI) were studied by ultrastructural morphometry and electron probe X-ray microanalysis. STI administered orally in drinking water for 14 days resulted in a 72% increase in the wet weight of the pancreas. This enlargement was due, largely, to an increase in acinar cell mass. Volume increases in the acinar cell mass and extra-acinar cell compartment were 72 and 30%, respectively. The estimated total number of acinar cells in the mean exocrine pancreas was 500 million in the control and 630 million in the experimental group, representing an increase of 27%. Acinar cell volume was 1,790 microns 3 for the control and 2,457 microns 3 for the STI group. The pronounced morphometric changes of the organelles in the STI group were: the mean nucleolar volume increased by 56%; the volume of zymogen granular mass per cell increased by 93%; the volume of the Golgi complex and the condensing vacuoles per cell increased by 52 and 100%, respectively, whereas the membrane area of the Golgi complex and the condensing vacuoles increased by 98 and 47%, respectively. Spectral analysis of seven elements (Na, Mg, P, S, Cl, K and Ca) showed significant changes for nuclei, zymogen granules and mitochondria following STI: nuclei showed Na, P, K increased; zymogen granules showed Na, P, S, K increased, Cl decreased; mitochondrial particles showed Mg, P, Cl, Ca increased, and the mitochondrial matrix showed S decreased. The persistent uptake of STI probably resulted in a continual release of a trophic hormone acting on pancreatic tissue components, consequently causing hyperplasia and hypertrophy of the exocrine pancreas to accommodate a heightened demand for synthesis of exportable proteins. PMID- 2305634 TI - Morphology of the porcine myometrium during parturition. AB - The ultrastructure of the porcine myometrium collected at well-defined stages during parturition was investigated by transmission electron microscopy. The morphology of the parturient myometrium resembled in general that in pregnant and non-pregnant pigs. The diameter of the smooth muscle cells was, however, about twice that of non-pregnant myometrium. Thick myofilaments were numerous. The number of caveolae seemed to be higher in parturient compared with non-pregnant and pregnant cells. Gap junctions occurred richly and were large, while the intrinsic innervation was very scanty. To conclude, the endocrinological changes in the pig taking place just prior to parturition, are translated into morphological changes by stimulating the formation of uterine gap junctions. This provides low-resistance pathways between the muscle cells and activates the myometrium for the delivery process. PMID- 2305635 TI - Collagen degradation and mucosal mast cell in endometrium of mouse uterus during early postpartum period. AB - On the morning of the day of parturition, several parts in the endometrium showed edema in which collagen birefringence was not observed, indicating that collagen degradation occurs firstly in the endematous area. Undegradated collagen might be redistributed wholly in the endometrium on postpartum day 1 when the area of endometrium has diminished. The number of mucosal mast cells in the endometrium did not fluctuate in parallel with the endometrial collagen-degrading process, suggesting that mucosal mast cells do not participate in the collagen degradation during the early postpartum period. PMID- 2305636 TI - The primary care physician and thrombolytic therapy for acute myocardial infarction: comparison of intravenous streptokinase in community hospitals and the tertiary referral center. AB - From September 1982 through December 1987, 1012 patients were treated with intravenous streptokinase within 6 hours of acute myocardial infarction. Most of them (816/1012, 81 percent) were treated in community hospitals by primary care physicians. The remaining 196 (19 percent) were treated in the referral center, usually by a cardiologist. Cardiac catheterization within 2 days showed an open infarct artery in 87 percent of the community hospital and 83 percent of the referral center patients (P = NS). Predischarge ejection fraction was similar for community hospital and referral center patients (49 percent +/- 14 percent versus 51 percent +/- 14 percent, respectively), and there was a similar rate of bleeding complications (10 percent versus 13 percent, respectively). We conclude that primary physicians can use intravenous streptokinase effectively and safely in the treatment of patients in community hospitals. PMID- 2305637 TI - The association between marital adjustment and compliance with antihypertension regimens. AB - The purpose of this cross-sectional survey was to determine relations between marital adjustment as measured by the Dyadic Adjustment Scale and antihypertension compliance. From seven dependent measures, we found high marital adjustment scores to be significantly correlated with less obesity, lower frequency of forgetting blood pressure medications, and less cessation of blood pressure medicine. These effects were much larger in a younger subsample of respondents who were 28 to 50 years old. The Dyadic Adjustment Scale measures the respondent's perception of the degree of affection and consensus, cohesion, and satisfaction in marriage. We conclude that the perception of positive marital interaction and communication ultimately contributes to controlled blood pressure by helping the patient to maintain healthy weight and to remember and continue taking blood pressure medication. PMID- 2305638 TI - Breast screening practices among primary physicians: reality and potential. AB - Increased use of regular screening mammograms and clinical breast examinations (CBE) among women aged 40 years and more could have a dramatic impact on mortality from breast cancer, but patient and physician barriers to mammography impede its acceptance. We conducted a survey of 300 primary care physicians to assess their knowledge, attitudes, beliefs, and breast screening practices. Our results show that only 71 percent of the respondents ordered mammograms for all women aged 50 to 75 years, which is the recommendation by the National Cancer Institute and American Cancer Society. Approximately 46 percent of respondents performed CBE on all women patients aged 50 to 75 years. Inadequate patient insurance coverage, equivocal radiology reports, patient reluctance or worry, and patient embarrassment all appear to be barriers to physicians' utilization of breast screening. PMID- 2305639 TI - Smoking cessation during pregnancy: strategies used by Michigan family physicians. AB - This study reports the attitudes and strategies of members of the Michigan Academy of Family Physicians about their antismoking interventions for pregnant smokers. Of the 978 physicians surveyed, 607 (62 percent) returned completed questionnaires. Three hundred twenty-three (53 percent) were not practicing obstetrics. The remaining 284 physicians currently practicing obstetrics constituted the study group. Ninety-four percent of these physicians routinely assessed smoking status at the first prenatal visit. Ninety-eight percent advised pregnant smokers to quit smoking during pregnancy. The most frequently used method of intervention was personal counseling (97 percent), followed by referral to smoking cessation clinics (40 percent), and behavior modification (20 percent). Fifty-seven percent of the physicians reported using antismoking pamphlets, and 30 percent used antismoking posters designed for pregnant women. Only 11 percent of the physicians surveyed were generally satisfied with the effectiveness of their current methods. Nonetheless, 97 percent were convinced that the benefits of smoking cessation during pregnancy merited their efforts. The physicians in this sample consistently have advised their pregnant smokers to quit, but most believe there is a need for more effective smoking cessation methods. PMID- 2305640 TI - Prenatal care--a serious national dilemma. PMID- 2305642 TI - Fin de siecle: four modest wishes for family practice. PMID- 2305641 TI - Twenty years: more questions than answers. Non amo te. PMID- 2305643 TI - The interstitial fluid pressure monitor: a device to aid in the determination of patient fluid requirements. AB - Assessment of patient fluid requirements is often difficult. Previous basic as well as clinical studies have suggested that interstitial fluid pressure (IFP) correlates with interstitial fluid volume and can be measured with a catheter placed in the subcutaneous space. We constructed a simple device to monitor IFP. The mean IFP for 7 healthy volunteers was -1.19 mmHg. IFP was measured in 25 patients at presentation and as clinical status evolved. Patients were classified as hypervolemic, normovolemic, or hypovolemic on the basis of their clinical status, the evolution of their condition, and laboratory and radiographic data. IFP correlation with assigned classification was statistically significant. The results suggest IFP can be measured readily and reliably in humans and is sensitive for reflecting the hydration of the interstitial compartment. This measure can assist in the determination of patient fluid requirements. PMID- 2305644 TI - Postpartum Pap smear. PMID- 2305646 TI - NSAIDs. PMID- 2305645 TI - Editorial: any more cordials to the drooping spirit? PMID- 2305647 TI - The effect of nimodipine on ICP and CBF in patients with normal-pressure hydrocephalus. AB - Eight patients with normal-pressure hydrocephalus (NPH) were studied. The resting mean arterial blood pressure (MABP) was 100 (90-125) mmHg and the mean intracranial pressure (ICP) was 11 (5-17) mmHg. ICP and MABP were continuously measured intraventricularly and intra-arterially, respectively. Changes in global cerebral blood flow (CBF) were estimated by the arteriovenous oxygen difference method. Intravenous nimodipine (15 microgram/kg/hour) was given in the first 2 hours and 30 microgram/kg/hour in the next 2 hours. MABP was reduced 23 (4-47) mmHg (p less than 0.05). ICP was increased 3 (0-10) mmHg (p less than 0.05). CBF was unchanged in the group on the whole, but in 4 of patients a major drop in perfusion pressure was seen, and CBF decreased 6, 11, 23 and 34%, respectively. Thus these findings underline the importance of maintaining the perfusion pressure under treatment with nimodipine. PMID- 2305648 TI - Head injuries coexistent with pelvic or lower extremity fractures--early or delayed osteosynthesis. AB - The authors compared the results of a retrospective analysis of two groups of head-injured patients who had coexistent pelvic or lower extremity fractures. One group was treated with early osteosynthesis within the first 12 hours after trauma, simultaneously with neurosurgical treatment, while the second group was treated neurosurgically and osteosynthesis was postponed for 4 to 10 days. The second group revealed a higher mortality, which was due to fat embolism. We conclude that early osteosynthesis is the treatment of choice in patients with coexistent head injury and lower extremity fractures. PMID- 2305649 TI - Gas bubbles within acute intracranial epidural haematomas. AB - In order to assess the actual incidence of gas bubbles trapped within acute intracranial epidural haematomas, as revealed by computed tomography (CT) of the skull, a series of 204 patients with surgically verified epidural haematomas was retrospectively reviewed. Gas bubbles were observed on CT scan in 22.5% of the cases, with the incidence rising to 37% when CT scanners of the last generation were employed. The available data failed to demonstrate the actual source of intracranial gas. No correlation was found between the presence of gas bubbles and outcome. No patient in the whole series showed any sign of intracranial infection. PMID- 2305650 TI - Cranioplasty with a frozen and autoclaved bone flap. AB - 27 cases of cranioplasty with autogenous bone grafts stored in a deep-freezer and autoclaved before use are reported. The results of follow-up for an average period of one year were satisfactory from the standpoint of brain protection and cosmetic reconstruction. A small area of absorption of grafted bone was observed in two cases on the follow-up skull roentgenograms. No serious complications were seen except in one case, whose bone flap had to be removed due to an epidural abscess. Experiments revealed that deep-freezing and autoclaving had only minimal effects on bone structure, although osteocytes degenerated. Autogenous bone flap after deep-freezing is a useful material for cranioplasty but sterilization before use is indispensable. Autoclaving is a simple method for sterilization of the flap, available in any operating theatre. It does not increase the risk of postoperative complications such as infection or absorption. PMID- 2305651 TI - Management of thoraco-lumbar fractures. AB - The immediate surgical goals in the treatment of thoraco-lumbar fractures are decompression of compromised neural structures and stabilization of the vertebral column. If more sophisticated instrumentation is available, e.g. A.O.-fixateur interne or instrument set according to Kluger, stable reposition and reformation of compressed vertebral bodies also becomes possible. The long-term goals are to prevent delayed onset of spinal deformity, pain, and further neurological deficit. Early operative stabilization also shortens hospitalization time and allows immediate ambulation, thus lessening pulmonary, vascular, urological, and psychological complications. The Department of Neurosurgery, Sher-I-Kashmir Institute of Medical Sciences, treated 75 cases of thoraco-lumbar fractures. Out of 75 cases 63 were operated upon: 32 cases by spinal fusion alone and 31 by a combined procedure of decompression and posterior spinal fusion with fibular graft. 52 showed evidence of recovery ranging from moderate to excellent in a follow-up of 2-3 years. Thus surgery resulted not only in giving a stable spine to patients but also good improvement of neurodeficits. Our experiences demonstrate that operative treatment of thoraco-lumbar fractures can give satisfactory results even in situations where sophisticated instrumentation is not available. PMID- 2305653 TI - Radiation-induced meningiomas and their proliferative activity. Cytokinetic study using bromodeoxyuridine. AB - Two cases of meningiomas, which are considered to have been caused by the preceding irradiation, are reported. In both cases, the cytokinetic study of the tumour using bromodeoxyuridine (BrdU) was performed. The percent of the tumour cells in the S phase of the cell cycle was less than 1% in both cases. The low labelling indices might suggest a relatively slow growing potential of these tumours, though the radiation-induced meningiomas were reported as being rapidly growing and malignant. PMID- 2305652 TI - Subarachnoid buprenorphine administered by implantable micropumps. AB - This report concerns 23 patients, the majority of whom are suffering from low back and chest pain caused by chest, urological or gynaecological cancer. These patients were treated with subarachnoid buprenorphine, administered in a single bolus or by slow infusion from micropumps, at a daily dose adapted to patients need (0.06-0.15 mg). The painful symptomatology was successfully controlled in all the cases treated, allowing the patients to live a virtually normal life. In no cases was respiratory depression or tolerance observed. PMID- 2305655 TI - Induced hyperthermia in brain tissue: comparison between contact Nd:YAG laser system and automatically controlled high frequency current. AB - Concerning hyperthermia treatment, knowledge of time-temperature and of temperature distributions within tumour volumes is essential in order to obtain the maximal therapeutic effect. New techniques are developed to overcome these difficulties. Two different heat sources, the contact Nd:YAG laser system and the automatically controlled high frequency current are investigated. In a defined volume of 1 cm3, the laser system reaches 45 degrees C after 1.8 s exposure with 15 W output power. The high frequency current reaches 45 degrees C with 48 s exposition with 18.75 W output current. Both heat sources present an exponential decrease of the temperature profile depending on the distance and prove efficient for inducing anti-tumoural hyperthermia. The tissue heat clearance is compensated for by intermittent laser and high frequency current application. PMID- 2305656 TI - Neuroendocrinological aspects of neurosurgery. Proceedings of the Third Advanced Seminar in Neurosurgical Research. Venice, April 30-May 1, 1987. PMID- 2305654 TI - Nimodipine: evidence for clinically significant gastrointestinal side-effects. AB - Nimodipine, now widely used for treatment and prevention of cerebrovascular spasm, is regarded as a safe drug. Despite a preferential action on cerebral vessels, there is clinical and experimental evidence of effects on systemic vascular and intestinal smooth muscle cells. Gastro-intestinal side-effects, however, have not been reported in clinical studies dealing with treatment of vasospasm following subarachnoid haemorrhage. We report on a patient with subarachnoid haemorrhage who developed an acute life-threatening pseudo obstruction of the colon, a variant of adynamic ileus, while being treated with intravenous nimodipine. The relationship between this complication and calcium antagonist therapy is discussed and therapeutic strategies are presented. We conclude that neurosurgeons and neurologists should be aware of calcium antagonist--related ileus in patients treated with nimodipine. PMID- 2305657 TI - The hypothalamus: new ideas on an old structure. PMID- 2305659 TI - Obtaining a sexual history. PMID- 2305658 TI - Intrasellar pressure. PMID- 2305660 TI - Panic disorder. PMID- 2305661 TI - Circumcision: the debate continues. PMID- 2305662 TI - The circumcision controversy. PMID- 2305663 TI - Routine neonatal circumcision: boundary of ritual and science. PMID- 2305664 TI - Screening for depression. PMID- 2305665 TI - Solitary pulmonary metastasis from melanoma. AB - Malignant melanoma often presents with multiple-organ involvement. Pulmonary metastases are present in more than 50 percent of patients with a diagnosis of melanoma at autopsy. Metastases to the lung may be solitary or multiple. Computed tomographic scanning is the most sensitive radiologic method for detecting these pulmonary lesions. PMID- 2305666 TI - Sulindac suppression of colorectal polyps in Gardner's syndrome. AB - Sulindac causes both regression and suppression of colorectal polyps in patients with Gardner's syndrome and familial polyposis coli. Three patients with Gardner's syndrome and multiple colonic polyps had complete regression of polyps after two to three months of sulindac therapy. The implication that sulindac may prevent colorectal cancer and prophylactic surgery in patients with hereditary polyps of the colon is intriguing but has not yet been substantiated. PMID- 2305667 TI - New requirements for tampon labeling. PMID- 2305668 TI - Losing the freedom to choose pharmacy services. PMID- 2305669 TI - Compliance-related problems in the ambulatory population. AB - When prescription drugs are taken in the correct dose and the correct manner, they have great potential for improving the quality of medical care, but inappropriate and incorrect administration of these drugs can lead to severe health problems. Risk factors for problems related to prescription drug compliance were examined in a cross-sectional retrospective study (n = 1017) of ambulatory individuals who had undergone a Brown Bag Prescription Evaluation Program consultation. A pharmacist interviewer assessed drug-related problems such as duplication of drug product, overutilization and underutilization of medication, drug interactions, and side effects. Associations between specific medication-related problems and patient characteristics (demographics, medical history, and insurance status) were studied. Factors that appear to be associated with compliance problems include a patient's level of understanding of both medication instructions and the drug therapy, length of time since last physician visit, length of time on medication, total number of medications, and number of drug allergies. The class of medication taken was also found to be a significant predictor of excess risk. The age and sex of an individual appear to have little association with the development of compliance-related problems. The study reinforces the need for frequent patient contact with a health care professional and the value of educating the patient about the medication regimen. PMID- 2305670 TI - Building cooperation with physicians: an interview with Charles Fortner. Interview by Joyce Leinberger Mitchell. PMID- 2305672 TI - Members endorse training for pharmacy technicians. PMID- 2305671 TI - DUE should be multidisciplinary. PMID- 2305673 TI - Formulating a marketing plan: finding the patients who are looking for you. PMID- 2305674 TI - AIDS research grants given to 18 communities. PMID- 2305675 TI - Electrostatic effects in asbestos sampling. II: Comparison of theory and experiment. AB - A series of calculations was conducted to estimate the degree and type of electrostatic interactions that might occur with electrically charged asbestos samplers collecting charged particles. Relatively simple theoretical models were constructed assuming only charge-charge electrostatic interactions between a charged particle and a charged sampler. The results of these calculations were compared with some experimental measurements and the agreement between the two allowed some confidence in predicting behavior trends. Under conditions where both the particles and the sampler are charged, the nonconductive sampler exhibits increased particle loss, especially near the filter edge, and increased variability of the particle deposit. The variability of the deposit also tends to be greatest near the filter edge. Under similar conditions, conductive cowled samplers also can be expected to exhibit losses in particle deposit, especially near the filter edge. The variability over the filter surface, however, is less than for the nonconductive cowl. Particle collection onto the sampler filter generally is expected to be greatest for isokinetic, isoaxial sampling conditions. Particle collection on the filter decreases with lower sampling flow rates, lower air velocities near the sampler inlet, and increased turbulence near the inlet. PMID- 2305676 TI - Multicellular model for contaminant dispersion and ventilation effectiveness with application for oxygen deficiency in a confined space. AB - Multicellular models were developed to predict contaminant dispersion in a three dimensional (3-D) space. The method utilized in this study was patterned after models which have been developed for water pollution in lakes and streams. This approach involved (1) design of cell structures to accommodate the geometry and mass flow characteristics of the 3-D space and (2) approximation of dispersion coefficients to describe contaminant transport in addition to that resulting from mass flow between cells. The dispersion model utilized a mass balance equation to predict contaminant dispersion as a function of time. The computer model was evaluated against experimental data for oxygen deficiency inside a ventilated confined space (CS) model. Eight test cases of ventilation design for the CS model were tested for each of three contaminant release (nitrogen to cause oxygen deficiency) characteristics: (1) purging (oxygen recovery from an initial deficiency); (2) steady state; and (3) variable rate. The dispersion model did a reasonably good job of predicting oxygen concentrations for different locations (cells) in the CS model. The primary limitations of this multicellular method are associated with experimental approximations of flow patterns and dispersion coefficients. PMID- 2305677 TI - Indoor firing range air quality: results of a facility design survey. AB - A survey of 611 indoor firing ranges identified features of range design, operation, and maintenance that could affect air quality, a concern because of the lead composition of ammunition fired at the ranges. Features examined included the number of firing positions, location and type of air-handling equipment, maintenance practices, and other standard operating procedures (SOPs). Analysis of the data from the 339 valid responses showed that these ranges vary widely in design, construction, number of firing positions, and frequency of use. Most of these ranges were constructed years ago to the standards in force at the time. Consequently, they do not include many features specified in current standards. Findings from the survey suggest two possible options for ranges concerned about the lead exposure level: design upgrades and SOP changes. Retrofits are costly and design solutions must rely on existing criteria, many of which need verification to ensure their adequacy. Also, more research is needed to define the relationships between ventilation system design and lead exposures at the firing line. A lower cost, more expedient solution is to establish a program of prevention through changes in SOP, such as prohibition of unjacketed lead bullets or establishment of a regular program to monitor the proper operation of ventilation systems. Technology to enhance these preventive measures is being investigated. Possible products include devices for real-time monitoring of ambient air quality and personal lead dosage monitors. This study has underscored the need for further site studies to verify design criteria and to collect chemical and physical data that will help define the nature and extent of problems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305678 TI - Measurement of organic vapors at sub-TLV concentrations using fast gas chromatography. AB - Gas chromatography usually is considered too slow a method to be useful for real time or near real-time monitoring. If the chromatographic system is optimized for speed, however, it is possible to reduce retention times significantly. Recently, a fast gas chromatograph (GC) was described that allows many simple separations to be completed in 10 sec or less. The system features a gas-cooled, electrically heated, capillary cold trap that focuses the sample as an extremely narrow band at the front of the column. In this study the fast GC was used to measure the concentrations of benzene, toluene, and xylene in test atmospheres generated in the laboratory. The measurements then were compared to simultaneous measurements made with a conventional GC. At concentrations ranging from the threshold limit value (TLV) to one-tenth of the TLV, the fast GC decreased retention times by a factor of 10- to 100-fold relative to the conventional GC, with no loss of precision or accuracy. These results indicate that it may be feasible to develop a high-speed monitoring system based on a GC design similar to the one in this study. PMID- 2305679 TI - Evaluation of the GMD systems, Inc., thermally-desorbable diffusional dosimeter for monitoring methyl chloride. AB - The GMD Systems, Inc., thermally-desorbable diffusional dosimeter using Anasorb GM solid sorbent was evaluated for monitoring methyl chloride (CH3Cl) in the workplace. The effects of CH3Cl concentration; dosimeter exposure time; relative humidity, temperature, and face velocity during exposure; excursion exposure behavior; and storage temperature and duration after collection were investigated. Only extremely low face velocities (0.020 m/sec) and storage periods of over 8 days at room temperature or of around 30 days at reduced (refrigerator or freezer) temperatures caused sample degradation. Side-by-side measurements of CH3Cl using the diffusional monitor and a validated charcoal tube method under field conditions yielded statistically indistinguishable results. This diffusional monitor used in combination with Anasorb GM solid sorbent is a satisfactory means of determining CH3Cl exposures in the workplace. PMID- 2305680 TI - Usefulness of the hyperventilation test in stable exertional angina pectoris in selecting medical therapy. AB - To assess the prevalence of abnormal coronary vasoconstriction in stable exertional angina and to evaluate whether the presence of increased coronary tone may have therapeutic implications, we studied 83 consecutive patients with typical exertional angina, positive response to exercise stress testing and documented coronary artery disease. Abnormal coronary vasoconstriction was induced by a hyperventilation test in 16 patients (group I) while the remaining 67 had a negative response (group II). No differences were observed between the 2 groups with regard to clinical, exercise and angiographic data. All group I patients and 16 patients in group II repeated hyperventilation and exercise tests after the administration of dihydropyridine-type calcium antagonists (7 patients nifedipine, 9 patients felodipine). After treatment 15 of 16 group I patients had a negative response to the hyperventilation test. The total exercise duration was significantly increased (278 +/- 183 vs 554 +/- 248 seconds; p less than 0.001) with higher values of rate pressure product at peak exercise (168 +/- 47 vs 235 +/- 67 mm Hg x beats/min/100; p less than 0.0025). In group II no significant differences were observed between pre- and posttreatment values for total exercise duration (244 +/- 210 vs 308 +/- 243 seconds) and rate pressure product at peak exercise (170 +/- 46 vs 188 +/- 56 mm Hg x beats/min/100). These data show that the hyperventilation test can be used to select a subset of patients with stable exertional angina and detectable abnormal coronary vasoconstriction who will improve their exercise tolerance with coronary vasodilator treatment. PMID- 2305681 TI - Percutaneous transluminal coronary angioplasty in the setting of large intracoronary thrombi. AB - A cohort of 112 consecutive patients with angiographically defined intracoronary thrombi was treated with percutaneous transluminal coronary angioplasty and followed prospectively to determine early and late outcomes. Coronary angioplasty using a treatment modality of intravenous and intracoronary heparin, antiplatelet agents and prolonged inflations with oversized balloons (balloon:vessel ratio, 1.2:1) resulted in clinical success in 103 patients (92%) at hospital discharge. No periprocedural thrombolytic therapy was used and prolonged pretreatment with heparin was not routinely used. Four patients (3.5%) required elective coronary bypass surgery, and 4 patients (3.5%) required emergency coronary artery bypass grafting because of abrupt closure. Late clinical follow-up (mean 7 months) was available in 99 of the 103 successfully treated patients (96%). Seventy-three percent of patients were asymptomatic at follow-up, and 27% had class I or II angina. No patients had a late myocardial infarction. Elective coronary artery bypass surgery was required in 3 patients (3%) and repeat coronary angioplasty in 17 patients (17%). There were 2 late cardiac deaths at 7 months. Ninety-four patients (95%) had an event free follow-up defined as absence of coronary artery bypass surgery, myocardial infarction or death. In conclusion, coronary angioplasty alone, using intracoronary heparin and prolonged balloon inflations with relatively oversized balloons may be helpful to achieve a high initial success rate, low incidence of in-hospital complications and excellent long-term results in patients with intracoronary thrombus. PMID- 2305682 TI - Medical costs of coronary artery disease in the United States. AB - A model has been developed to determine the cost of coronary artery disease (CAD) based on the 5 primary events identified in the Framingham Study: acute myocardial infarction, angina pectoris, unstable angina pectoris, sudden death and nonsudden death. The costs for diagnostic and therapeutic service for patients with CAD were linked to medical decision algorithms outlining the diagnosis and management of patients with CAD. Because CAD is a changing illness not represented by a single event, the algorithm tracked patients for 5 years after the time of diagnosis, or until death, to develop average cost estimates. The estimated 5-year costs (in 1986 United States dollars) of the 5 CAD events were: acute myocardial infarction $51,211, angina pectoris $24,980, unstable angina pectoris $40,581, sudden death $9,078 and nonsudden death $19,697. The costs of major CAD surgical procedures were also calculated because of their impact on health care costs for patients with CAD. These include: coronary artery bypass surgery per case over 5 years $32,465, and angioplasty per case over 5 years $26,916. The high cost of CAD reflects the improved technology and more effective and expensive therapies now available. PMID- 2305683 TI - Spontaneous sustained ventricular tachyarrhythmias during treatment with type IA antiarrhythmic agents. AB - Twenty-six patients who developed their first clinical episode of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) while taking type IA antiarrhythmic agents for more benign rhythm disturbances were rechallenged with the identical drug during electrophysiologic testing. Patients with these new drug-associated spontaneous ventricular arrhythmias often manifested a preexisting substrate for such arrhythmias: sustained VT or VF was induced in 65% of patients at baseline, and in 58% of patients when tested with their previously taken antiarrhythmic drug. Among those without inducible sustained ventricular arrhythmias in the drug-free state, 78% remained free of inducible sustained arrhythmias when tested with the same drug they had been taking at the time of the clinical arrhythmia. Even patients without a definable electrophysiologic substrate for sustained VT or VF remained at risk for arrhythmia recurrence if treated with alternative antiarrhythmic medications: 40% of such patients who continued to receive an antiarrhythmic agent different from that being administered when their clinical VT or VF occurred had recurrent spontaneous ventricular tachyarrhythmias during follow-up. Thus, patients with drug associated clinical sustained ventricular tachycardias form a heterogenous group that should be evaluated individually and not empirically managed for a "proarrhythmic effect" simply by antiarrhythmic drug withdrawal or drug substitution. PMID- 2305684 TI - Changes in cardiac output determined by continuous-wave Doppler echocardiography during propafenone or mexiletine drug testing. AB - Antiarrhythmic drugs may induce congestive heart failure in patients with malignant ventricular arrhythmias and depressed left ventricular (LV) function. Whether Doppler echocardiography can detect drug-induced depression in LV function was assessed. Continuous-wave Doppler measurements of ascending aortic blood flow velocity were obtained in 16 patients while not receiving antiarrhythmic drugs on 2 consecutive days to assess day-to-day variability, as well as while receiving maximally tolerated oral doses of mexiletine (11 patients) and propafenone (9 patients). While receiving propafenone, a drug with moderate negative inotropic activity, peak flow velocity declined by 9 +/- 8% (p less than 0.05), the flow velocity integral (termed stroke distance, representing stroke volume) declined by 8 +/- 11% (p less than 0.10), the rate-corrected stroke distance declined by 9 +/- 8% (p less than 0.02) and the minute distance, representing cardiac output, declined by 10 +/- 12% (p less than 0.05). In contrast, while receiving mexiletine, a drug with minimal negative inotropic activity, none of these parameters changed significantly. Five of 9 patients (56%) treated with propafenone showed a decline in rate-corrected stroke distance exceeding the 95% confidence limit of day-to-day variability, which was +/- 13 percent. Two of these 5 patients developed clinical signs of congestive heart failure. Continuous-wave Doppler echocardiography can detect antiarrhythmic drug induced LV dysfunction and may be used to anticipate the development of significant clinically overt congestive heart failure. PMID- 2305685 TI - Electrophysiologic determinants of recurrent atrial flutter after successful termination by overdrive pacing. AB - The potential ability of electrophysiologic abnormalities to predict recurrence of atrial flutter was evaluated. Twenty-five patients with chronic atrial flutter resistant to combined digitalis and quinidine therapy were studied electrophysiologically after restoration of sinus rhythm by overdrive pacing or by eventual direct current cardioversion. Recurrence of atrial flutter was observed in 12 patients during a mean follow-up period of 17 months (range 3 to 50). Electrophysiologic testing included programmed high right atrial stimulation at a paced drive cycle length of 600 ms and incremental pacing up to 200-ms paced intervals. When coupling intervals of 90% of the drive cycle length were compared to coupling intervals of 48% of the drive cycle length, the increase in S1A1 interval, defined as the interval between the stimulus artifact and the atrial activation near the atrioventricular junction, was greater in patients with subsequent recurrence of atrial flutter (47 +/- 11 vs 21 +/- 18 ms). Stepwise logistic regression analysis identified the S1A1 increase to be the sole independent predictor of recurrence (p = 0.0082) while previous episodes of atrial flutter or the presence of organic heart disease were identified as dependent variables. Reclassification showed a 91% sensitivity and a 92% specificity. Correct classification was achieved in 92% of patients. The initiation of atrial dysrhythmia had no predictive value. The assessment of the S1A1 interval by programmed atrial stimulation appears helpful in delineating the patient risk of recurrent atrial flutter after termination by overdrive pacing. PMID- 2305686 TI - Percutaneous double balloon valvotomy for severe rheumatic mitral stenosis. AB - Percutaneous double balloon valvotomy for severe rheumatic mitral stenosis was successfully performed in 281 of 285 consecutive patients. The changes evoked were a decrease of the mean transvalvular gradient from 16 +/- 7 to 5 +/- 3 mm Hg, an increase in cardiac output from 3.8 +/- 1.0 liters/min to 5.4 +/- 1.5 liters/min and an increase in mitral valve area from 0.86 +/- 0.24 cm2 to 2.41 +/ 0.54 cm2. The mean pulmonary artery pressure decreased from 37 +/- 13 mm Hg to 27 +/- 12 mm Hg and the pulmonary vascular resistance decreased from 307 +/- 181 to 238 +/- 122 dynes/s/cm-5. Symptomatic improvement occurred in 272 of the 285 (95%) patients. There were 3 procedure-related deaths (1%). Postdilatation mitral regurgitation was not significant in most patients. Therefore, this procedure can be performed at a low risk with effective results and a fast recovery. PMID- 2305687 TI - Prognostic significance of radionuclide-assessed diastolic function in hypertrophic cardiomyopathy. AB - To evaluate the prognostic significance of diastolic function in hypertrophic cardiomyopathy (HC), technetium-99m gated equilibrium radionuclide angiography, acquired in list mode, was performed in 161 patients. Five diastolic indexes were calculated. During 3.0 +/- 1.9 years, 13 patients had disease-related deaths. With univariate analysis, these patients were younger (29 +/- 20 vs 42 +/- 16 years; p less than 0.05), had a higher incidence of syncope (p less than 0.025), dyspnea (p less than 0.001), reduced peak filling rate (2.9 +/- 0.9 vs 3.4 +/- 1.0 end-diastolic volume/s; p = 0.09) with increased relative filling volume during the rapid filling period (80 +/- 7 vs 75 +/- 12%; p = 0.06) and decreased atrial contribution (17 +/- 7 vs 22 +/- 11%; p = 0.07). Stepwise discriminant analysis revealed that young age at diagnosis, syncope at diagnosis, reduced peak ejection rate, positive family history, reduced peak filling rate, increased relative filling volume by peak filling rate and concentric left ventricular hypertrophy were the most statistically significant (p = 0.0001) predictors of disease-related death (sensitivity 92%, specificity 76%, accuracy 77%, positive predictive value 25%). Discriminant analysis excluding the diastolic indexes, however, showed similar predictability (sensitivity 92%, specificity 76%, accuracy 78%, positive predictive value 26%). To obtain more homogeneous groups for analysis, patients were classified as survivors (116) or electrically unstable (40), including sudden death, out-of-hospital ventricular fibrillation and nonsustained ventricular tachycardia during 48-hour ambulatory electrocardiography, and heart failure death or cardiac transplant (5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305688 TI - Bradycardia-mediated tachyarrhythmias in congenital heart disease and responses to chronic pacing at physiologic rates. AB - The coexistence of bradycardia and a tachyarrhythmia may preclude effective pharmacologic treatment of 1 arrhythmia without paradoxic aggravation of the other. This study evaluated the potential relation between the 2 types of arrhythmias and the effect of conventional modes and rates of pacing for bradycardia on the frequency of the associated tachyarrhythmias. Twenty-one young patients, aged 2 to 19 (mean 11) years with congenital heart disease and a tachyarrhythmia occurring in the setting of chronic bradycardia were studied. The effects of pacing were evaluated by comparison of the number of episodes of clinical tachycardia during the 12-month intervals before and after pacemaker implantation. During these intervals, antiarrhythmic drug therapy was not altered. Patients were analyzed as independent groups, based on the type of tachyarrhythmia: supraventricular (n = 5), atrial flutter (n = 9) and ventricular (n = 7). The modes of chronic pacing were AAI (n = 4), DDD (n = 6) and VVI (n = 11). The prevention of bradycardia by pacing was associated with a significant decrease in the frequency of supraventricular (p = 0.008) and ventricular (p = 0.02) tachyarrhythmias. However, the frequency of atrial flutter was not altered. Prevention of tachycardia was more frequently associated with the AAI and DDD modes of pacing compared to VVI (p = 0.08). Pacing represents an effective therapy for certain tachyarrhythmias associated with chronic bradycardia, although critical modes may be required. PMID- 2305689 TI - Cardiac transplantation in patients with preexisting neoplastic diseases. AB - Cardiac transplantation has traditionally been reserved for individuals with end stage congestive heart failure (CHF) in whom there is no history of other life threatening systemic disorders. In most transplant centers, patients with a history of malignancy and severe heart failure have not been considered acceptable candidates for cardiac transplantation. In the last 4 years at Stanford University Medical Center, 8 cardiac transplants have been performed in 7 patients with a history of neoplastic disease. Six of these patients had already received treatment for lymphoproliferative disorders and in 1 case, a patient underwent a transplant after treatment for adenocarcinoma of the colon. Six of the 7 patients were discharged from the hospital and in that group, the 1 year posttransplant survival rate was 71%. This was comparable to an overall 1 year survival rate of 80% for patients undergoing a cardiac transplant at our center during the same period of time. At follow-up averaging over 2 years, there has been 1 case of recurrent neoplasia. One patient with evidence of radiation induced pulmonary damage died of respiratory failure 2 days after transplantation. One patient required retransplantation because of intractable rejection and subsequently died from infectious complications. Immunosuppressive therapy in these patients has not been associated with an increased risk for neoplastic recurrence or for the development of posttransplant lymphoproliferative disorders. The current study demonstrates that in a carefully selected group, previously treated neoplastic disease should not represent a contraindication to cardiac transplantation. PMID- 2305691 TI - Left main coronary artery disease progression after percutaneous transluminal coronary angioplasty. PMID- 2305690 TI - Usefulness of silent ischemia, ventricular tachycardia, and complex ventricular arrhythmias in predicting new coronary events in elderly patients with coronary artery disease or systemic hypertension. PMID- 2305692 TI - Inotropic response to dobutamine in elderly patients with decompensated congestive heart failure. PMID- 2305694 TI - Prevalence of significant congenital heart defects in children of parents with Fallot's tetralogy. PMID- 2305693 TI - Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy. PMID- 2305695 TI - Depressed left ventricular systolic ejection force in hypothyroidism. PMID- 2305696 TI - False-negative diagnosis of proximal aortic dissection by computed tomography or angiography and possible explanations based on transesophageal echocardiographic findings. PMID- 2305697 TI - Atrial standstill after treadmill exercise test and unique response to isoproterenol infusion in recurrent postexercise syncope. PMID- 2305698 TI - Limited research funds and cardiac medicine without cardiac surgery. PMID- 2305699 TI - Pica as a presenting symptom in childhood celiac disease. AB - Persistent pica may be either a cause or a result of iron deficiency. Three children are described with long-standing pica and iron-deficiency anemia and in whom total villous atrophy consistent with celiac disease was found on jejunal biopsy. Additional findings included short stature, delayed bone age, and impaired xylose absorption. A dramatic growth spurt and complete resolution of pica were observed after a gluten-free diet. In these cases pica evidently resulted from iron deficiency secondary to malabsorption. Underlying celiac disease should be considered in children with persistent pica and growth failure even if gastrointestinal disturbances are minimal. PMID- 2305700 TI - Exercise intensity does not affect the composition of diet- and exercise-induced body mass loss. AB - The effect of caloric restriction (1200 kcal/d intake) in combination with high (High) (80-90% of peak VO2) or low (Low) (40-50% of peak VO2) exercise work rates on the composition of lost body mass was determined in 27 obese women (percent fat, 36.7 +/- 4.2%; mean +/- SD). All subjects trained 3 d/wk for 8 wk, with the High (n = 14) and Low (n = 13) groups exercising for 25 and 50 min/d, respectively. After posttesting there were no differences between the groups with respect to pre- to posttest changes (mean of combined groups) in body mass (-7%), fat-free mass (-10%), fat mass (-16%), percent fat (-10%), and sum of five skinfold-thickness measurements (-16%). This study suggests that with regard to conservation of fat-free mass, the selection of an exercise intensity for a diet and exercise regimen may be left to the preference of the clinician and/or dieter. PMID- 2305701 TI - Repeatability of 24-h energy expenditure measurements in humans by indirect calorimetry. AB - To estimate sources and extent of variation in energy expenditure (EE), as measured by indirect calorimetry in a room-sized human calorimeter, a number of 24-h measurements were compiled. Measured oxygen consumption and carbon dioxide production from alcohol combustion experiments averaged 101.5% of the theoretical value with a coefficient of variation (CV) of 1.4%. Experiment 1 consisted of four men who had the following averages: age, 41 y; height, 179 cm; weight, 84.6 kg; and fat, 23.5%. Five measurements, separated by 1 d, were made on each subject. Daily and basal EE averaged 2852 and 1691 kcal/d, respectively, with a within-subject CV of 2.7% and 2.4%, respectively. Experiment 2 consisted of five men who had the following averages: age, 48 y; height, 181.6 cm; weight, 87 kg; and fat, 23%. Five measurements made on each subject were separated by 1-3 wk. Daily and basal EE averaged 2619 and 1837 kcal/d, respectively, with a within subject CV of 4.6% and 2.9%, respectively. PMID- 2305702 TI - Effect of intensity of physical activity on body fatness and fat distribution. AB - To evaluate the effect of intensity of physical activity on body fatness and fat distribution, observations of 1366 women and 1257 men who participated in the 1981 Canada Fitness Survey were analyzed. Subjects were tested for energy expenditure of leisure-time activities and estimated maximal oxygen uptake (VO2max), body fatness was measured by subcutaneous skinfold thicknesses, and anthropometric measurements were made. Subjects of both sexes were categorized into four subgroups on the basis of their participation in leisure-time activities of various intensities. In general, subjects practicing vigorous activities on a regular basis had lower subcutaneous skinfold thicknesses and waist-to-hip ratios (WHRs) than those not performing these activities. These differences remained statistically significant after a covariance analysis was used to remove the effect of total energy expenditure of leisure-time activities on subcutaneous fat and fat distribution. Moreover, the WHR remained significantly lower in subjects performing high-intensity exercise after the effect of subcutaneous fat on fat distribution was adjusted for. PMID- 2305703 TI - Effect of a vegetable oil formula rich in linoleic acid on tissue fatty acid accretion in the brain, liver, plasma, and erythrocytes of infant piglets. AB - The effect of feeding sow-milk formula (SMF) or a vegetable-oil infant formula (FF) with minimal n-6 and n-3 long-chain polyenoic fatty acids (LCPs) but high linoleic acid (18:2n-6) and a high ratio of 18:2n-6 to linolenic acid (18:3n-3) on the fatty acids of brain lipid and liver, plasma, and red cell phospholipids was studied in piglets fed from birth for 5, 10, 15, or 25 d. Compared with SMF, FF reduced the concentrations of 18:1 and n-3 LCPs, especially 22:6n-3, in all tissues and increased 22:4n-6 in brain, liver, plasma, and red cell phosphatidylethanolamine. FF also increased 22:5n-6 in brain lipid, liver, and plasma but not in red cell phospholipids. Thus, changes in tissues capable of in situ desaturation were not completely reflected in the red cell phospholipids. The increased liver and brain n-6 LCP accretion in the FF piglets may suggest competent desaturation and possible inhibition of n-3 desaturation and/or acylation by dietary n-6 fatty acids. PMID- 2305704 TI - Antimicrobial proteins of maternal and cord sera and human milk in relation to maternal nutritional status. AB - Antimicrobial proteins in maternal and cord sera and sequential samples of human milk were studied in a group of 60 Chinese women to determine the degrees of passive immunity transferred from women of different nutritional status to their infants. Maternal malnutrition was characterized by low values for wt/ht2 and serum total protein and albumin. Maternal immunoglobulin (IgG) concentrations were not significantly different between well- and malnourished groups prepartum but were significantly different postpartum. Mean concentrations of cord IgG and lysozyme from well- and malnourished groups were not statistically different. During the first 7 d of lactation and most stages thereafter, mean concentrations of IgA; complements C3 and C4, and lysozyme in milk from the malnourished group were only half of those of the well-nourished group. Antimicrobial proteins transferred via milk to newborns may be influenced by the mother's nutritional status. PMID- 2305705 TI - Urinary methylmalonic acid excretion in infants fed formula or human milk. AB - Serum vitamin B-12 and urinary methylmalonic acid (MMA) concentrations were determined in 62 healthy infants aged 1-6 mo. Urinary MMA was inversely correlated with serum vitamin B-12 concentrations (r = -0.550, p less than 0.001); serum vitamin B-12 was higher (p less than 0.001) and urinary MMA concentrations were lower (p less than 0.001) in formula-fed infants than in infants fed human milk (from the breast). Human-milk-fed infants who had received supplemental formula had higher serum vitamin B-12 concentrations than did infants exclusively fed human milk. It is not clear whether the serum vitamin B 12 and urinary MMA concentrations in infants fed human milk reflect biochemical deficiency of vitamin B-12, and the clinical significance of these findings needs to be investigated. PMID- 2305706 TI - Stable-isotope methods for assessment of folate bioavailability. AB - Research was conducted to determine whether stable-isotope-labeled folates could be employed for studies of folate absorption and metabolism in human subjects. Two deuterium-labeled forms of folic acid were evaluated for simultaneous in vivo use, with quantification of relative bioavailability by measurement of urinary excretion of labeled folates. Adult male subjects (n = 11) were given saturation doses of 2 mg unlabeled folic acid/d for 7 d before the study. After an overnight fast each subject consumed 677 nmol each of 3',5'-labeled bideuterofolic acid and glutamate-labeled tetradeuterofolic acid. The 48-h urinary excretion of deuterated folates represented 5-6% of the ingested dose. The molar ratio of labeled folates in urine was not significantly different from the molar ratio in the ingested dose, which indicated equivalent absorption and metabolism of these labeled forms of the vitamin. These results support the validity of this protocol for in vivo studies of folate bioavailability. PMID- 2305707 TI - Plasma vitamin E and beta-carotene concentrations during radiochemotherapy preceding bone marrow transplantation. AB - Blood from 19 patients was examined for the essential antioxidants alpha tocopherol and beta-carotene before, during, and after bone marrow transplantation (BMT). Marrow ablation and immunosuppression for BMT conditioning was achieved by treatment with high-dose chemotherapy, mostly combined with total body irradiation. All patients required total parenteral nutrition beginning 1 wk before BMT. After conditioning therapy the concentration of absolute and lipid standardized alpha-tocopherol and beta-carotene in plasma decreased significantly, presumably as a result of an enhanced breakdown of these antioxidants. The loss of these lipid-soluble antioxidants has to be considered as a possible cause for early posttransplant organ toxicity. PMID- 2305708 TI - Milk selenium of rural African women: influence of maternal nutrition, parity, and length of lactation. AB - The selenium content of milk samples from rural Gambian women (n = 55) was evaluated as a function of parity, stage of lactation, and maternal nutrition. Samples were collected during periods of relative food abundance (dry season) and food scarcity (rainy season). Milk selenium was lower (p less than 0.01) in the rainy than in the dry season (208 vs 256 nmol/L, respectively). Milk selenium was similar in samples from women in early (1-6 mo postpartum) and late (13-19 mo postpartum) lactation. During late lactation, parity, which ranged from 1 to 11, was negatively correlated with milk selenium regardless of plane of maternal nutrition (p less than 0.02). Measures of protein, glutathione peroxidase, and total peroxidase were not affected by stage of lactation or parity. Glutathione peroxidase activity accounted for 38% of the peroxidase activity in milk. Results show that although length of lactation alone had little impact, milk selenium secretion was influenced by both maternal nutritional adequacy and parity of rural Gambian women. PMID- 2305709 TI - Influence of iron-deficiency anemia on selected thymus functions in mice: thymulin biological activity, T-cell subsets, and thymocyte proliferation. AB - To define the effects of iron deficiency on thymulin biological activity, T-cell subsets, and thymocyte proliferation, C57BL/6 female mice at weaning were fed an iron-deficient diet (10 mg Fe/kg diet), an iron-sufficient diet (50 mg Fe/kg diet), or restricted amounts of the iron-sufficient diet (the pair-fed group) for 40 d. Iron deficiency did not reduce the concentration of either serum or intracytoplasmic thymulin. Although T-cell subsets in the thymus were not altered, both the cortical and medullar regions were depleted of thymocytes. In the spleen iron deficiency (but not underfeeding) significantly reduced the percentage of L3T4+ cells, of Lyt-2+ cells, and thus of the overall T-cell population. However, it did not affect the ratio of L3T4+ to Lyt-2+ T cells. Thymocyte proliferation was significantly reduced at the concanavalin A (Con A) dose (10 mg/L) that produced maximal stimulation in control and pair-fed mice but not at low (7.5 mg/L) or high (15 mg/L) Con A concentrations. We conclude that the impairment in immune functions associated with iron deficiency is not due to an impairment in thymic endocrine function but rather to decreased immunocompetent lymphocytes. PMID- 2305710 TI - Dietary evaluation of patients with smell and/or taste disorders. AB - The impact of smell and taste disorders on dietary habits and nutritional status has received limited research attention. This paper reports findings obtained from questionnaires and diet records completed by 40 healthy subjects and 118 patients with chemosensory dysfunction. Chemosensory disorders were frequently associated with decreases in food acceptability. Although dietary responses to these dysfunctions varied greatly, patients with distorted or phantom smell and/or taste sensations tended to report weight loss whereas those with simple sensory loss were more likely to report weight gain. Indices derived from diet records did not indicate that either group of patients was at substantial nutritional risk, but food frequency responses and estimates of body mass index were consistent with patient reports of changes in dietary patterns and weight. In addition, marked weight change and aberrant dietary practices were noted in individual patients. Thus, there were indications that chemosensory dysfunction may be associated with nutritionally important dietary alterations. PMID- 2305711 TI - A new predictive equation for resting energy expenditure in healthy individuals. AB - A predictive equation for resting energy expenditure (REE) was derived from data from 498 healthy subjects, including females (n = 247) and males (n = 251), aged 19-78 y (45 +/- 14 y, mean +/- SD). Normal-weight (n = 264) and obese (n = 234) individuals were studied and REE was measured by indirect calorimetry. Multiple regression analyses were employed to drive relationships between REE and weight, height, and age for both men and women (R2 = 0.71): REE = 9.99 x weight + 6.25 x height - 4.92 x age + 166 x sex (males, 1; females, 0) - 161. Simplification of this formula and separation by sex did not affect its predictive value: REE (males) = 10 x weight (kg) + 6.25 x height (cm) - 5 x age (y) + 5; REE (females) = 10 x weight (kg) + 6.25 x height (cm) - 5 x age (y) - 161. The inclusion of relative body weight and body-weight distribution did not significantly improve the predictive value of these equations. The Harris-Benedict Equations derived in 1919 overestimated measured REE by 5% (p less than 0.01). Fat-free mass (FFM) was the best single predictor of REE (R2 = 0.64): REE = 19.7 x FFM + 413. Weight also was closely correlated with REE (R2 = 0.56): REE = 15.1 x weight + 371. PMID- 2305712 TI - Nutritional adaptation in man: general introduction and concepts. AB - The aim of this paper is to clarify thinking on the subject of nutritional adaptation. A series of concepts and questions are proposed with, as examples, some of the responses that occur to low intakes of energy and protein. The main conclusions are first, that in dealing with human beings value judgements cannot be avoided, but to avoid sterile discussion they must be separated from objective descriptions of adaptive responses. Second, the way ahead lies in examining the shape of the responses of different functions to different degrees and kinds of stress. Objective studies of this kind do not require use of the word adaptation. PMID- 2305714 TI - Iron status in Hispanics. PMID- 2305715 TI - 5-Fluorouracil and high-dose folinic acid as second-line chemotherapy in head and neck cancer. AB - Experimental and clinical data support the concomitant use of 5-fluorouracil (5 FU) and high-dose folinic acid (HDFA). To verify the role of such a combination in far advanced head and neck cancer, we performed a phase II study employing weekly HDFA, 500 mg/m2 in 2-h infusions, and 5-FU, 600 mg/m2 bolus injection. Twenty-seven evaluable patients with recurrent disease entered the study. One complete response, seven partial responses, 10 stable disease, and nine progressions were observed: the overall response rate was 29.6%. Oral mucositis and diarrhea were major side effects; five patients discontinued the treatment due to toxicity; no deaths correlated to the treatment were detected. Considering the characteristics of our patients, the 5-FU/HDFA combination has shown a satisfactory antitumoral activity, but toxicity was similar to other chemotherapy regimens. PMID- 2305713 TI - Metabolism and nutritional adaptation to altered intakes of energy substrates. AB - Adaptive changes in energy expenditure to changes in energy intake are far less than previously believed once changes in body weight and physical activity are taken into account. Alterations in metabolic efficiency of +/- 10% in total energy expenditure are the limits of what can normally be expected on prolonged under- or overfeeding. The supposed twofold variation in energy requirements of adults is based on measurements of food intake, which, despite involving weighted intakes over a week, cannot be considered realistic. Subtle differences in the energetic responses to fat, protein, and carbohydrate signify the different effective energetic contribution of isoenergetic substrates and may account for the propensity to obesity in individuals and societies on a high-fat diet. PMID- 2305716 TI - Phase II study of teniposide (VM26) in cutaneous T-cell lymphomas. AB - A Phase II study of teniposide (VM26) in cutaneous T-cell lymphoma (CTCL) was performed in 15 patients affected by stage III, IV according to TNM (mycosis fungoides or Sezary syndrome). All patients were pretreated, and VM26 was administered at a dose of 100 mg/m2 weekly for at least 3 weeks. Objective responses were observed in 40% of the patients, with two complete responses lasting 26 and 46 months. The drug was well tolerated in elderly patients and deserves further evaluation either for inclusion in first-line combination regimens or for palliative treatment in heavily pretreated or elderly patients. PMID- 2305717 TI - Phase II evaluation of 4'deoxydoxorubicin in advanced renal cell carcinoma. AB - 4'Deoxydoxorubicin was evaluated in patients with advanced renal carcinoma. Only one partial remission was noted, and no significant cardiac toxicity was seen on serial evaluation of ejection fractions. Appropriate dose escalations were performed. PMID- 2305718 TI - Pharmacokinetics of very high-dose oral melphalan in cancer patients. AB - The pharmacokinetics and systemic availability of melphalan after high-dose oral administration with and without 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) or etoposide were examined in three patients undergoing autologous bone marrow transplantation. Patient 1 (advanced melanoma) received melphalan at 80 mg/m2/day p.o. on days -6, -5, and -4, followed by BCNU at 300 mg/m2/day i.v. on days -3, 2, and -1 prior to bone marrow transplantation. Patient 2 (advanced colon carcinoma) received melphalan at 75 mg/m2/day p.o. on days -3, -2, and -1. Patient 3 (advanced refractory lymphoma) received etoposide at 800 mg/m2/day i.v. on days -7, -5, and -3, followed by melphalan at 157 mg/m2/day p.o. on days -2 and -1. Melphalan was administered as a bolus oral dose, using 2-mg tablets. Blood samples were collected at 0, 5, 10, 15, 30, and 45 min and 1, 2, 3, 4, 6, 8, 12, and 24 h after each dose of melphalan. Peak plasma melphalan concentrations in the three patients ranged from 0.354 (patient 2) to 1.768 micrograms/ml (patient 1). Plasma melphalan concentration X time products (C x Ts) showed extreme variability in one patient (patient 2), ranging from 0.76 to 4.48 micrograms.h/ml. To determine the relative systemic availability of orally administered melphalan, i.v. C X Ts proportional to the p.o. doses were extrapolated from previously reported i.v. bolus pharmacokinetic data. The p.o.:i.v. plasma C X T ratios for high-dose melphalan ranged between 0.09 (patient 3) and 0.58 (patient 2). Although these C X T data suggest a dose response for orally administered melphalan, the systemic availability of these high p.o. melphalan doses was extremely variable, both within and between study patients. Thus, we cannot recommend the use of high-dose p.o. melphalan regimens in patients undergoing autologous bone marrow transplantation. PMID- 2305719 TI - Phase II trial of 10-Edam in patients with advanced colorectal carcinoma. AB - 10-Edam (10-ethyl-10-deaza-aminopterin), an antifolate derivative, was administered to 14 chemotherapy-naive patients with advanced colorectal carcinoma. The drug was given weekly by intravenous route at an initial dose of 80 mg/m2, with escalation or attenuation according to tolerance. Mucositis was dose limiting and occurred in 11 of 14 patients (78.6%). Removal from the study was required in one patient due to progressive pulmonary fibrosis that was histologically identical to methotrexate-induced lung damage. Toxicity was otherwise mild to moderate and included diarrhea, constipation, abdominal discomfort, anorexia, nausea/vomiting, rash, and fatigue. There were no responses to 10-Edam in this study, 95% confidence interval (0-0.23). Stable disease was achieved in four patients; the remaining 10 patients demonstrated progression within 9 weeks of initiating systemic therapy. 10-Edam employed at this dosage and schedule was not effective as a treatment against advanced colorectal carcinoma. PMID- 2305721 TI - Electrochemical treatment of cancer. II: Effect of electrophoretic influence on adriamycin. AB - Electrochemical treatment of cancer with DC electrodes changes the microenvironment of the cancer cells by electrophoresis. They may deteriorate and resorb. In larger neoplasms, the effects can be enhanced by electrophoresis of a chemotherapeutic agent. Adriamycin delivered into an electropositive neoplasm electrode will move outwards in the neoplastic area in a high concentration. When given intravenously and the neoplasm electrode is electronegative, the systemic effects may be diminished. The agent is instead accumulated in the neoplastic region in a high concentration. This principle may be used to reduce systemic effects of charged chemotherapeutic compounds. In this preliminary study of cancer in 14 patients, incurable with surgery, radiation treatment, or chemotherapy, beneficial effects were obtained after combined electrochemical treatment and the use of Adriamycin. PMID- 2305720 TI - Screening test for hormone sensitivity by the autoradiographic method using cell mats. AB - We developed an autoradiographic screening test for hormone sensitivity of single cell suspensions of tumor tissues on cell mats, which inhibited the growth of normal cells alone. We applied this method to our newly established KSE-1 line derived from esophageal carcinoma and compared this method with well-established cytoplasmic and nuclear assays. Our assay, though taking longer to implement and providing only qualitative information, requires significantly smaller specimens than the current biochemical assay and will predict the hormone sensitivity of only viable neoplastic cells. PMID- 2305722 TI - Dialogues with Henry. PMID- 2305723 TI - Stress in residency. PMID- 2305724 TI - Management of croup. PMID- 2305725 TI - Growth velocity values measured during short observation periods may obscure effects of treatment of growth failure. PMID- 2305726 TI - Late sudden unexpected deaths in hospitalized infants with bronchopulmonary dysplasia. PMID- 2305727 TI - Attitudes regarding parental presence during medical procedures. PMID- 2305728 TI - Gonadal steroids and somatic growth. PMID- 2305729 TI - Informed consent for lumbar puncture: an alternative. PMID- 2305730 TI - Revised pediatric code card. PMID- 2305732 TI - Increasing the antibiotic spectrum in the treatment of impetigo. PMID- 2305731 TI - Etiology and therapy of impetigo: reconsidered. PMID- 2305733 TI - Total serum IgE levels in children with pertussis. AB - Total serum IgE levels were evaluated in 20 children with pertussis. Increased levels of serum IgE were observed in the group of children between the ages of 3 and 12 years, while normal levels of serum IgE were detected in the groups of children between birth and 24 months old and between 13 and 24 months old. A further and significant increment of serum IgE levels was also found after 10 days of hospitalization. PMID- 2305734 TI - Protective efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid-conjugate vaccine. AB - We estimated the relative protective efficacy of Haemophilus influenzae type b polysaccharide (PRP) vaccine and PRP-diphtheria toxoid-conjugate (PRP-D) vaccine using data from reports of cases of invasive Haemophilus disease occurring in vaccinated children submitted to the Food and Drug Administration, Rockville, Md, and Washington University, St Louis, Mo. During the first 13 months following licensure of each of the vaccines, there were 127 cases reported in recipients of PRP vaccine vs 17 cases in recipients of PRP-D vaccine. The total number of reported cases for each vaccine is not necessarily comparable, since the extent of vaccine use in the population and the extent of reporting of cases may have been different during the two periods. However, the proportion of reported cases occurring equal to or 14 days or more after vaccination (a period considered sufficient to develop immunity) was significantly greater for PRP vaccine (106 [83%] of 127 cases) compared with PRP-D vaccine (7 [41%] of 17 cases). Based on the ratio of late-onset to early-onset cases observed for PRP vaccine, we would have expected 50 late-onset cases after PRP-D vaccination. Since only 7 late onset PRP-D vaccine failures were reported (86% fewer than expected), the data suggest that PRP-D vaccine was more effective in preventing disease 14 days or more after vaccination than was PRP vaccine. PMID- 2305735 TI - Are adolescents getting smarter about acquired immunodeficiency syndrome? Changes in knowledge and attitude over the past 5 years. AB - A survey was administered to 1543 adolescents from southeastern Wisconsin to assess their knowledge, attitudes, and beliefs regarding acquired immunodeficiency syndrome (AIDS) and persons with the disease. Responses were compared with those of other studies involving adolescents using identical or similar test items. Results of the study demonstrate that knowledge of AIDS and of the modes of human immunodeficiency virus transmission have increased dramatically over the past 5 years. Ninety-eight percent of high school students in this study understood the modes of transmission and that merely touching a person with AIDS will not transmit the virus. However, results also revealed that many negative biases remain toward people who have been infected with human immunodeficiency virus. Forty-five percent of the students believed that homosexuals and intravenous drug users were "getting what they deserve." Recommendations are made that future educational efforts focus on changes in attitudes and behaviors in relation to adolescents' previously acquired knowledge of AIDS. PMID- 2305736 TI - Suicide attempts among adolescent drug users. AB - Substance use has been identified as a significant risk factor in nonfatal and fatal suicides during adolescence. A comprehensive questionnaire on patterns of alcohol and other drug use, early childhood and nuclear family psychological and behavioral history, and previous suicidal attempts was completed by 298 (88%) of 340 outpatient adolescent substance abusers in three geographic regions east of the Mississippi River. An abbreviated Beck Depression Inventory was included to ascertain current symptoms of depressed mood. Adolescents admitting to a previous suicide attempt (30%) were compared with two age- and sex-matched samples. Substance abusers were three times as likely as a normative population of non drug-using age- and sex-matched peers to make a suicide attempt. Thirty-three percent of attempts reported occurred prior to high school. Both the wish to hurt oneself and actual suicide attempts were found to increase significantly after the initiation of substance use. Forty percent used drugs within 8 hours before the suicide attempt, and 23% of attempters reported that their families continued to have a firearm with ammunition in the home following the suicide attempt. Adolescent substance abusers who had attempted suicide were significantly more likely than a matched group of nonattempters in the same drug treatment facility to: (1) complain of usually feeling "blue" or sad (depressed affect) during early childhood, (2) identify important childhood behavioral problems, (3) identify long-standing self-perceived impaired self-concept, and (4) identify serious parental problems, such as chronic depression or alcoholism. Self-perceived chronic loneliness in childhood appears to be a singularly important initiator of adolescent drug use and subsequent suicide attempts among drug abusers. PMID- 2305737 TI - Evaluations of diapers containing absorbent gelling material with conventional disposable diapers in newborn infants. AB - We evaluated 149 infants diapered in either conventional cellulose core disposable diapers or diapers containing cellulose core with absorbent gelling material. The infants were evaluated from 1 day of age to 14 weeks of age for the prevalence and severity of diaper dermatitis. We identified a low prevalence of diaper dermatitis throughout the study period. At 14 weeks of age, we noted that infants in diapers containing absorbent gelling material had significantly less diaper dermatitis than those in conventional disposable diapers. Despite the overall low prevalence of diaper dermatitis in the newborn period, 7 of 204 infants evaluated had small skin erosions in the diaper area noted within the first 4 days of age. Both diaper types were associated with infants with erosions. This surprisingly high incidence of erosions in newborn infants suggests previously undocumented increased skin fragility of full-term infants. PMID- 2305738 TI - Does breast-feeding protect the hypothyroid infant whose condition is diagnosed by newborn screening? AB - Neuropsychological abilities at 1, 3, 5, and 6 years of age were compared in 107 children with congenital hypothyroidism identified by newborn screening who had been either breast-fed or formula fed during infancy. The thyroxine level was significantly higher in breast-fed children than formula-fed children at 1 and 2 months of age, but the level was not higher later during the first year of life. Controlling for parent IQ, socioeconomic status, and dose level, no differences in overall neuropsychological functioning were observed. Children with ectopic glands showed a significant advantage with breast-feeding on several tasks at 3 years of age. These results signify that thyroxine levels in infancy from breast feeding are not necessarily reflected in improved intellectual functioning later in childhood. PMID- 2305739 TI - Extra hospital stay and antibiotic usage with nosocomial coagulase-negative staphylococcal bacteremia in two neonatal intensive care unit populations. AB - Coagulase-negative staphylococci were the leading cause of nosocomial bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and Children's Hospital, Boston, Mass, in 1982. To determine the consequences of these nosocomial bacteremias, a cohort study was conducted in which two comparison subjects were matched with each of 38 bacteremic infants by hospital, birth weight within 100 g, and nearest date of discharge. To adjust for duration of stay in the hospital, it was also required that both comparison subjects have survived and remained in the hospital for as long as the time until bacteremia occurred in the bacteremic infant. The average day of onset of bacteremia was the 20th hospital day. Despite having similar birth weights and comparable severity of underlying illness, bacteremic infants remained in the hospital for an average of 19.8 days longer than the nonbacteremic comparison subjects (77.3 vs 57.5 days). The bacteremic patients received antibiotics for an average of 11.2 more days than the nonbacteremic infants. Vancomycin hydrochloride was given to 20 (52.6%) of the bacteremic patients but only 4 (5.3%) of the comparison patients. All of the comparison subjects and 37 of the 38 infants with bacteremia survived. Thus, nosocomial bacteremia with coagulase-negative staphylococci is a late complication of hospitalization that occurs in infants who are already relatively long-term survivors. This bacteremia appears to be associated with substantially longer hospital stay and antibiotic therapy but little, if any, excess mortality. PMID- 2305740 TI - Medical evaluation of abused and neglected children. AB - Children who have been abused and neglected may have a variety of medical problems not apparent to a social worker or other nonmedical professional investigating the allegations. A joint project between a state child protective agency and an urban teaching hospital was undertaken to provide for the systematic medical screening of all children brought to the agency before their placement in foster care. These children received a complete medical evaluation with emphasis on documenting the abuse and neglect and also were screened for other medical problems. A total of 5181 children were evaluated. Forty-four percent of these children had some medical problem, including anemia, otitis media, sexually transmitted infections, and lead poisoning. Additional instances of abuse and neglect were identified and documented. This systematic evaluation allows for the optimal identification, documentation, and treatment of abuse, neglect, and other medical problems that may affect a child's outcome and adaptation. PMID- 2305741 TI - Radiological cases of the month. Congenital complete absence of the left pulmonary artery and hypoplastic left lung. PMID- 2305742 TI - Radiological cases of the month. Toy 'jack' aspiration into the hypopharynx. PMID- 2305743 TI - Severe respiratory syncytial virus infection in older children. AB - Serious respiratory syncytial virus (RSV) disease requiring hospitalization occurs primarily in infants younger than 12 months. The incidence, risk factors, and clinical features in older children have not been studied extensively. Of 282 children hospitalized at our institution with severe RSV disease during a 3-year period, 62 (22%) were older than 12 months. These 62 older children were matched for sex, onset of illness, and hospital location with 62 hospitalized children younger than 12 months with proved RSV infection. Older children had underlying chronic disease more commonly than younger children (47 of 62 vs 24 of 62). Chronic illnesses in older children included bronchopulmonary dysplasia and/or reactive airway disease (34 of 47), congenital heart disease (9 of 47), gastrointestinal disease (7 of 47), and genetic disorders (7 of 47). Three of the four deaths from RSV infection occurred in older children; all four had underlying disease (three with congenital heart disease and one with biliary atresia). We conclude that children older than 12 months with underlying disease are at increased risk for serious or fatal RSV infection and are not always protected by previous RSV disease. Such older children should be considered candidates for passive or active immunoprophylaxis against RSV infection as such agents become available. PMID- 2305744 TI - Detection of interleukin 1 beta but not tumor necrosis factor-alpha in cerebrospinal fluid of children with aseptic meningitis. AB - Tumor necrosis factor-alpha and interleukin 1 beta have been shown to be mediators of meningeal inflammation in animal models of bacterial meningitis. The presence of both cytokines in cerebrospinal fluid (CSF) of patients with bacterial meningitis has been documented recently. In this study, we measured concentrations of interleukin 1 beta and tumor necrosis factor-alpha in CSF samples from 36 patients with nonbacterial (aseptic) meningitis, 13 of whom had culture-proved enteroviral meningitis, and from 14 control patients. None of the samples from patients with aseptic meningitis and from the controls had detectable tumor necrosis factor activity in CSF. Thirty-two (89%) of 36 patients with aseptic meningitis had detectable interleukin 1 beta in CSF (mean +/- SEM, 48 +/- 11 pg/mL). These concentrations were significantly smaller than those previously reported in patients with bacterial meningitis (944 +/- 128 pg/mL). Only 2 of the 14 control patients had detectable CSF interleukin 1 beta concentrations of 21 and 42 pg/mL. A significant correlation was evident between interleukin-1 beta concentrations and white blood cell counts in the CSF of patients with aseptic meningitis. Our data suggest that the initial events of CSF inflammation in children with aseptic meningitis are different than those in patients with bacterial meningitis, and the participation of these two cytokines, especially tumor necrosis factor-alpha, is less critical to the process. PMID- 2305745 TI - Tumor necrosis factor alpha and interleukin 1 beta in synovial fluid of infants and children with suppurative arthritis. AB - Tumor necrosis factor alpha and interleukin 1 beta concentrations were measured in synovial fluid of 24 infants and children with diagnoses of suppurative arthritis (n = 16) and other kinds of arthritis (n = 8). Large concentrations of tumor necrosis factor alpha (range, 100 to 85,000 pg/mL) were found in 12 (75%) of 16 patients with bacterial infection and in none of the patients with noninfectious origins. Large concentrations of interleukin 1 beta (greater than 200 pg/mL) were found in 15 (94%) of 16 patients with bacterial infection and in none of the other patients. In the latter group, small concentrations of interleukin 1 (range, 40 to 120 pg/mL) were present in 5 (63%) of 8 patients. Serum samples obtained simultaneously were negative for both cytokines. Tumor necrosis factor alpha and interleukin 1 beta concentrations correlated significantly and with leukocyte counts in synovial fluid. We conclude that large concentrations of tumor necrosis factor alpha and interleukin 1 beta are produced locally in patients with suppurative arthritis and they may be potentially useful in differentiating this condition from other kinds of arthritis. PMID- 2305746 TI - Children's television-viewing habits and the family environment. AB - Pediatricians are encouraged to modify the impact of television on children, based on the assumption that parents mediate children's viewing habits through the home environment. Sixty-six parents of children aged 3 to 8 years responded to an interviewer-administered questionnaire. Responses to questions on family environment were compared with reported childhood viewing of educational programming (Public Broadcasting Service) and the child's television-viewing hours. Most homes surveyed had a videocassette recorder, cable television, and more than one television set. Frequent parental discussion of program content with children was reported by 38% of respondents. Availability of television and parent-child discussion of content were not correlated with viewing hours or viewing Public Broadcasting Service. Frequent use of television as a distraction for the child correlated positively with viewing hours. Viewing Public Broadcasting Service correlated negatively with parent-child coviewing and with use of television as a form of entertainment. Children's own television viewing content correlated positively with viewing Public Broadcasting Service. Of all measured factors in the home environment, parental attitudes were most closely associated with children's viewing habits. PMID- 2305747 TI - Calcium retention from milk-based infant formulas, whey-hydrolysate formula, and human milk in weanling rhesus monkeys. AB - An adequate supply of calcium is important for normal bone mineralization in infants. Special infant formulas have been developed to treat infants with a high risk of developing allergy. Similar to other diets, it is important that these products are nutritionally adequate. We have measured calcium retention from a new formula based on whey hydrolysate and compared it with conventional formulas, using extrinsic labeling with calcium 47 and the weanling rhesus monkey as an animal model. Retention of calcium was similar for all formulas studied: 45% +/- 4% (mean +/- SEM) from whey-hydrolysate, 47% +/- 2% from whey-predominant, and 53% +/- 7% from casein-predominant formula. Calcium retention from human milk, 72% +/- 3%, was significantly higher than from formula. Using these retention values and the calcium concentrations of the diets, infant formula and human milk deliver approximately equal amounts of calcium to the infant. PMID- 2305748 TI - Neurologic sequelae of open-heart surgery in children. An 'irritating question'. AB - As pediatric cardiac surgical techniques have improved in recent years, mortality rates have dropped and attention has turned to residual morbidity, especially neurologic sequelae. Although the majority of children undergoing open-heart surgery for correction of congenital heart defects apparently emerge with no adverse consequences, a small percentage suffer permanent neurologic injury (seizures, motor disorders). Another small and not well-defined population may be left with disorders of higher cortical function, such as mental retardation or learning disabilities. A survey of six major pediatric cardiac surgery units in North America was undertaken in 1988-1989 to ascertain current approaches to the detection and management of neurologic sequelae of pediatric open-heart surgery. All units reported seeing a small but definite incidence of postoperative neurologic symptoms, including alterations of consciousness, seizures, and localized abnormalities such as hemiparesis or delayed choreoathetoid syndromes. Postoperative neuroimaging procedures have shown a disturbing incidence of hypoxic-ischemic encephalopathy, unsuspected cerebral atrophy, and subdural hematomas. Pathogenesis may include factors related to preoperative brain anomalies and/or hypoxic insults, altered cerebral blood flow and metabolism during hypothermic cardiopulmonary bypass with or without total circulatory arrest, embolization, and low cardiac output states postoperatively. Further studies are needed to examine the mechanisms of injury and to develop techniques to minimize the occurrence of these sequelae, as they may be associated with life long neurologic disability and reduced quality of life. PMID- 2305749 TI - Magnetic resonance imaging of the brain in infants and children before and after cardiac surgery. A prospective study. AB - We assessed the morphologic findings of the brain prospectively before and after cardiac surgery using magnetic resonance imaging. There were 12 patients with acyanotic and 6 with cyanotic heart disease. There were 2 deaths, and 1 patient did not have to undergo postoperative magnetic resonance imaging. The study group consisted of 15 patients completing both the preoperative and postoperative magnetic resonance imagings. All patients in the study group underwent moderate hypothermic cardiopulmonary bypass using a nonpulsatile membrane oxygenator. The mean (+/- SD) cardiopulmonary bypass time was 100 +/- 55 minutes. Ten of the preoperative studies were interpreted as normal. One third (5 of 15) of the patients showed ventriculomegaly and dilatation of the subarachnoid spaces on preoperative magnetic resonance images. Measurements of the preoperative and postoperative magnetic resonance images showed a postoperative increase in the bicaudate and third ventricular diameters. Four patients in the study group developed postoperative subdural hematomas. The subdural hematomas were small and caused no demonstrable mass effect on magnetic resonance imaging. One patient had a preoperative white matter infarction. There was 1 patient with a postoperative infarction. PMID- 2305750 TI - Religious objection to autopsy. An ethical dilemma for medical examiners. AB - In recent years, religious objection to autopsy has become an ethical dilemma for medical examiners. We present two cases that illustrate these dilemmas, and we also review the history and legal considerations of religious objection to autopsy. PMID- 2305752 TI - Anterior thoracic wall trauma in elderly homicide victims. The "CPR defense". AB - During the course of medicolegal postmortem examinations, forensic pathologists often encounter the sequelae of cardiopulmonary resuscitation (CPR) that was administered by medical and paramedical personnel. A wide variety of CPR-related injuries have been described since the institution nearly 30 years ago of this now common-place emergency technique. The forensic pathologist must be aware of both typical and unusual CPR-related trauma patterns in order to differentiate between injury produced during emergency therapy procedures and injury sustained through other mechanisms (for example, during an assault or an accident). This article describes two recent separate and unrelated incidents in which an elderly woman was murdered. In each instance, bony injuries of the anterior thoracic wall structures were identified during the autopsy. Defense attorneys in each case attempted to use these injuries as proof that their accused clients had performed external cardiac massage on their victims, thus indicating that the homicides had not been intentional, and that the perpetrators showed remorse. These cases are presented, with a discussion of the typical features of CPR-related thoracic wall trauma as compared with willfully inflicted injury. PMID- 2305751 TI - Recovery of decomposed and skeletal human remains in the "Green River Murder" Investigation. Implications for medical examiner/coroner and police. AB - The Green River Murder Investigation in King County, Washington, is currently the longest active serial murder investigation in U.S. history. During its course, over 26 separate scenes with from one to five victims each have been processed. The experience of the authors is presented in order to acquaint other agencies with techniques of outdoor scene processing that have evolved during recovery of remains from Green River and other skeletal cases. PMID- 2305754 TI - Retinal hemorrhage in an infant after cardiopulmonary resuscitation. AB - Unexplained retinal hemorrhages in infants are usually indicative of child abuse. We present the case of an infant with retinal hemorrhages following cardiopulmonary resuscitation, who had not been abused. Cardiopulmonary resuscitation should be added to the list of causes of retinal hemorrhages in infants and children. PMID- 2305753 TI - Chronic extradural haemorrhage. A case report and brief literature review. AB - A case of chronic extradural haemorrhage with a presumed time interval of 5-6 weeks between injury and diagnosis at postmortem examination is presented. The literature relating to this entity has been reviewed, and relevant features commented upon, including time intervals, age, sex, location, clinical features, pathological findings, associated skull fractures, mechanisms involved, and the source of the bleeding. PMID- 2305755 TI - Massive fat and necrotic bone marrow embolization in a previously undiagnosed patient with sickle cell disease. AB - A case of sickle cell disease diagnosed postmortem is described. A 37-year-old black woman presented with anemia, respiratory distress, and abdominal and back pain. Death followed an intramuscular injection of iron, and anaphylaxis was clinically diagnosed. At autopsy, massive fat and necrotic bone marrow embolization of pulmonary and renal vessels was found. In the vertebral column, multifocal areas of ischemic necrosis were present, and proved to be the source of this embolization. Sickled red cells appeared in bone marrow sinusoids, and signs of disseminated intravascular coagulation were present. PMID- 2305756 TI - Xenolingual autoeroticism. AB - Reports in the medical literature of autoeroticism seldom describe episodes that are nontraumatic or nonlethal. Reports of bestiality typically involve descriptions of sexual relationships between humans and animals, and are analyzed through psychological methods. No reports of bestiality involving the use of animal tissue for erotic purposes have been published. We report the use of a deer tongue as a masturbatory tool. PMID- 2305757 TI - Disinterments. Their value and associated problems. AB - This article presents our experience with several cases of disinterment, including reasons for disinterment, the methodology involved, and the value of this activity in solving medicolegal problems. PMID- 2305758 TI - Towards a developmental view of end-stage renal disease. AB - Although much study has been devoted to the psychological adjustment of patients treated for end-stage renal disease (ESRD), relatively little attention has been paid to developmental perspectives of the patient with ESRD. ESRD can be divided into four phases: the onset stage, an initial treatment phase, a maturity phase, and a stage of death and dying. The tasks confronted in each phase are dissimilar. The roles of compliance and the medical staff may change in each phase. In particular, the stresses of the maturity phase may be balanced in a complex, enmeshed, and precarious fashion. A developmental view implies that adaptive mechanisms at one stage may be maladaptive in others, and that relationships and ethical viewpoints may change radically as the response to the disease and its treatment progresses. The developmental phase must be taken into consideration when decisions are made in the care of patients with ESRD. PMID- 2305759 TI - Patient, family, and staff responses to end-stage renal disease. AB - The course of a chronic illness is composed of discrete developmental phases, which influence the relationship of the patient to the care-giving system, and the tasks required of patients, families, and medical staff. Family characteristics may influence medical outcome. Compliance may be a critical factor in mediating the biological response to social phenomena. The relationship of the patient to his or her family and the health-care system may change dramatically through the developmental phases of the chronic disease. The case of a patient with end-stage renal disease (ESRD) illustrating these concepts is presented. PMID- 2305760 TI - Quality-of-life issues for end-stage renal disease patients. AB - Given the importance of making comparisons regarding quality-of-life issues for end-stage renal disease (ESRD) patients, the research presented here first compares 766 patients who experienced one of the following therapies for at least 1 year: (1) center hemodialysis, (2) continuous ambulatory peritoneal dialysis (CAPD), or (3) successful transplantation (one cohort of patients from the 1970s, a second cohort from 1980 to 1984). Second, since the most recent transplant group was randomized to two alternative immunosuppressive drug regimens, we compared the quality of life of the patients on cyclosporine/prednisone therapy (N = 51) and the patients on a conventional immunosuppressive therapy (antilymphocyte globulin/prednisone/azathioprine; N = 40). Patients had to be age 19 to 56 years and nondiabetic to be included in this research. Data were collected with survey questionnaires containing measures of physical, emotional, and social well-being, vocational rehabilitation, sexual adjustment, and marital and family adjustment. Case mix or background differences were controlled as much as possible using an analysis of covariance (ANCOVA) and comparison of adjusted means. Our results show that the successful transplant patients scored higher than both dialysis groups (P less than 0.05 for nine of 11 measures) on almost all variables, demonstrating a higher quality of life. The effect of a failed transplant on quality of life was also examined. In terms of the recent transplant patients, the cyclosporine group scored consistently higher on all physical, emotional, and social well-being measures (excluding males' vocational rehabilitation), although differences are not always significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305761 TI - Mortality and causes of death in patients with end-stage renal failure. AB - Using data from the Michigan Kidney Registry, the survival of patients with end stage renal disease (ESRD) was evaluated by multivariate analysis. Black patients had a significantly better outcome overall. A significantly worse outcome was found for older patients and diabetics, among both races and for black females. Causes of death were analyzed for dialysis patients and specific comments address discontinuation of dialysis leading to death. PMID- 2305762 TI - Ethical issues in the initiation and termination of treatment. AB - This report addresses the ethical issues involved in decisions to initiate and terminate treatment. A general framework is constructed and then two illustrative cases are discussed. The framework is developed in three stages. First, the issue of guiding ethical principles is examined, with a multiple-principle approach being adopted. Second, common models of the care-giver/patient relationship (warrior, parental, contractual, covenantal) are identified, and their varying impacts on treatment decisions are explained and assessed. Third, specific criteria for determining when to initiate and terminate treatment are introduced. Two criteria (willingness and medical benefit) are commended in the context of initiating treatment, while three distinctions (willing v unwilling, passive v active, and terminal v nonterminal) are found to be particularly helpful when deciding if treatment should be terminated. Two illustrative cases involve end stage renal disease (ESRD). The first describes a noncompliant and abusive intravenous (IV) drug user on hemodialysis who wants to continue on dialysis and eventually receive a living-related donor kidney transplant. The second describes a patient's decisions to refuse feeding gastrostomy and jejunostomy, any further surgical or diagnostic intervention, and eventually dialysis-though only after a period of time when he wants dialysis alone to continue. PMID- 2305763 TI - Prospective peritoneal scintigraphy in patients beginning continuous ambulatory peritoneal dialysis. AB - Forty-eight adult patients without clinical evidence of inguinal or abdominal wall hernias underwent peritoneal scintigraphy shortly after beginning continuous ambulatory peritoneal dialysis (CAPD). Scintigraphically detectable subclinical structural defects involving the inguinal canal or abdominal wall were present in 14 patients. Within 5 months, four of these defects progressed to clinically significant CAPD-related structural complications. These patients could not be distinguished by clinical or scintigraphic criteria from the 10 patients with nonprogressive structural defects. No scintigraphic structural defects were detected in 34 patients, 30 of whom remained free of CAPD-related structural complications. Five patients developed symptomatic structural complications during follow-up in areas that had been scintigraphically normal at the onset of CAPD. We conclude that some CAPD-related structural complications arise de novo, while others represent progression of subclinical pre-existent structural abnormalities that can be detected by peritoneal scintigraphy. However, most asymptomatic scintigraphic defects do not progress to a symptomatic stage, limiting the usefulness of prospective peritoneal scintigraphy as a guide to recommend prophylactic repair of all asymptomatic structural defects in patients beginning CAPD. PMID- 2305764 TI - Renal vasodilatory response to intravenous glycine in the aging rat kidney. AB - Studies were performed in the awake, chronically catheterized male Sprague-Dawley rat to investigate renal hemodynamics in the baseline state and also in response to a large intravenous (IV) amino acid (glycine) load. Studies were performed in young adult rats (age 3 to 4 months), old rats (age 18 months), and senescent rats (age 22 to 24 months). Histologic evaluation of the kidney permitted a correlation between structural and functional changes with aging. Histology showed progressive glomerular damage (sclerosis) with aging. In 18-month-old rats, the glomerular filtration rate (GFR) was normal, which, considering the level of glomerular injury (only 64% normal glomeruli), must indicate heterogeneity of glomerular function, with some hyperfunctioning glomeruli. By 22 to 24 months of age (at which time approximately 50% mortality has occurred in males of this strain), GFR is substantially reduced, as is renal plasma flow rate (RPF). Severe glomerular damage was observed histologically (only 34% normal glomeruli), indicating widespread heterogeneity of glomerular function. Young adult rats displayed a substantial renal vasodilation in response to acute IV glycine infusion, which resulted in approximately 25% increases in GFR and RPF. The renal vascular responsivity to glycine was diminished at 18 months and was completely absent in 22- to 24-month-old rats. This altered renal vasodilatory response to glycine probably reflects both structural changes associated with aging and also the compensatory vasodilation of intact hyperfunctioning remnant nephrons as other nephrons are lost due to aging. PMID- 2305765 TI - Hypouricemia in acquired immunodeficiency syndrome. AB - Clinical evaluations of hypouricemia in patients with the acquired immunodeficiency syndrome (AIDS) have shown that it is a common disorder resulting from defective renal handling of uric acid. We prospectively studied renal urate handling in 23 patients and reviewed the records of 73 consecutive patients with AIDS or AIDS-related complex (ARC), who were seen in our AIDS clinic between March 1985 and April 1988, to determine the incidence, significance, and, when possible, the cause of hypouricemia. Hypouricemia was defined as serum urate less than or equal to 0.18 mmol/L (3 mg/dL). Renal clearance studies were performed in 23 patients, 10 hypouricemic and 13 nonhypouricemic. Eight patients (six with hypouricemia) underwent central venous pressure (CVP) monitoring, which was performed for clinical signs and symptoms of extracellular volume depletion. Fourteen (eight with hypouricemia) had daily urine urate measured. Hypouricemia was found in 21 (21.9%) of 96 patients. It was more common in females and intravenous (IV) drug abusers, and was associated with more opportunistic illnesses, particularly mycobacterium avium intracellulare (MAI) and cytomegalovirus (CMV) infections. Hypouricemia occurred in three patients with ARC and 18 patients with AIDS and was associated with cerebral atrophy in all 12 hypouricemic and 14 of 28 nonhypouricemic patients who had cranial computed tomography (CT) scans. During a comparable follow-up period, 71.4% of the hypouricemic as compared with 38.7% of nonhypouricemic patients died. Eleven developed hypouricemia as outpatients. Fractional excretion of uric acid (FEua) was elevated in the eight patients with CVP less than 1 cm of water, and in 10 of 10 with and nine of 13 without hypouricemia, despite CVP less than 1 cm water in eight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305766 TI - Subclavian vein stenosis and thrombosis: a potential serious complication in chronic hemodialysis patients. AB - One hundred ninety patients, 61 with acute renal failure and 129 with chronic renal failure, underwent hemodialysis using a total of 302 subclavian vein catheters. Local hematomas and sepsis (seven events) were the only acute complications. Subclavian vein stenosis and/or thrombosis had occurred and were shown in five of 44 patients who had arteriovenous access created distal to the venous outlet obstruction, resulting in the loss of three of five of these accesses. In view of the fact that subclavian vein stenosis or occlusion is not associated with any clinical findings and we were unable to identify any predisposing factors associated with the use of the catheters, all patients who have had previous subclavian vein catheters probably should be evaluated to determine the patency of the subclavian vein before creation of a permanent access in that arm. PMID- 2305767 TI - Two brothers with idiopathic membranous nephropathy and familial sensorineural deafness. AB - Genetic factors could play an important role in the pathogenesis of idiopathic membranous nephropathy, and a few cases of familial membranous nephropathy have been described: an increased incidence of some HLA antigens as DR3 and others has been reported. We present two brothers with idiopathic membranous nephropathy and sensorineural deafness. HLA typing was performed in the two patients and in the members of the family, and it showed the absence of linkage of an HLA antigen with the renal disease in the family. PMID- 2305769 TI - Organic dusts and lung diseases. Proceedings of an international workshop. Skokloster, Sweden, October 24-27, 1988. PMID- 2305768 TI - Splenic abscess in patients on hemodialysis. AB - We describe two patients on hemodialysis who developed staphylococcal splenic abscesses. Both patients previously had staphylococcal septicemia secondary to infection at the dialysis access site. We postulate that access-site infections may predispose hemodialysis patients to splenic abscess, and that these patients should be investigated for a splenic abscess if they should develop unexplained fever. PMID- 2305770 TI - Precipitins in bird breeder's disease: are they useful? PMID- 2305771 TI - Massive exposure to aeroallergens in dairy farming: radioimmunoassay results of dust collection during bedding chopping with culture confirmation. PMID- 2305772 TI - Atopy is a predisposing factor for chronic bronchitis among farmers. PMID- 2305773 TI - Bronchoalveolar lavage in persons acutely exposed to dust in the farm environment. PMID- 2305774 TI - The role of inflammatory mediators in airway edema and obstruction produced in guinea pigs exposed to inhaled endotoxin or cotton dusts. PMID- 2305775 TI - Can spores from molds and actinomycetes cause an organic dust toxic syndrome reaction? PMID- 2305777 TI - Investigation of bronchoalveolar lavage (BAL)-fluid in persons exposed to organic dusts. PMID- 2305776 TI - Organic dust toxic syndrome: a follow-up study. PMID- 2305778 TI - Organic dust toxic syndrome in Swedish farmers: symptoms, clinical findings, and exposure in 98 cases. PMID- 2305780 TI - Uptake of muramyl dipeptide by alveolar macrophages in experimental hypersensitivity pneumonitis. PMID- 2305781 TI - Questionnaire evaluating organic dust exposure. PMID- 2305779 TI - Bronchoalveolar lavage of pig farmers. PMID- 2305782 TI - Exposure pattern in relation to symptoms--clinical findings. PMID- 2305783 TI - Influence of atopy and smoking on symptoms--clinical findings. PMID- 2305784 TI - Guidelines for evaluation of clinical cases. PMID- 2305785 TI - Unifying concepts underlying the effects of organic dust exposures. AB - Defense mechanisms protect the lung very well from inhaled organic dusts. With sufficient exposure to certain dusts, however, susceptible individuals develop hypersensitivity pneumonitis (HP), the organic dust toxic syndrome (ODTS), or asthma. Mucous membrane irritation (MMI) bothers some individuals inhaling grain dust. Allergic asthma is caused by IgE-mediated immunologic responses to allergenic dust contaminants. ODTS can be explained by a nonimmunologic release of interleukin 1 (IL-1) and perhaps other endogenous pyrogens from alveolar macrophages by endotoxin or other ingredients of dusts. The pathogenesis of HP may involve IL-1 release combined with a specific immunological response by effector T-lymphocytes. MMI may be the result of an irritant effect not involving immune responses or mediators. PMID- 2305786 TI - Prevention of hazardous conditions in agriculture. PMID- 2305787 TI - Message from WHO: importance of research on organic dusts to the Workers' Health Program of the World Health Organization. PMID- 2305788 TI - Across-shift lung function changes among pig farmers. PMID- 2305789 TI - Respiratory symptoms and pulmonary function in Saskatchewan farmers. PMID- 2305790 TI - Cross-sectional study of respiratory symptoms in 1,175 Danish farmers. PMID- 2305791 TI - Study of bronchial hyperreactivity and loss of lung function in farmers. PMID- 2305792 TI - Relationship between respiratory symptoms and bronchial hyperreactivity in pig farmers. PMID- 2305793 TI - Bronchial hyperreactivity among pig and dairy farmers. AB - The presence of work-related symptoms, pulmonary functions, and bronchial reactivity were studied in farmers working with dairy animals or pigs. An increased incidence of the organic dust toxic syndrome, cough, and throat irritation was found. Pulmonary function baseline values were close to normal, and no significant decreases occurred over the work period. Bronchial reactivity was increased. PMID- 2305794 TI - Respiratory function in workers employed in animal food processing. PMID- 2305795 TI - Byssinosis study among 250 textile mill workers in Jakarta. PMID- 2305796 TI - Assessment of U.S. poultry worker respiratory risks. PMID- 2305797 TI - Lower respiratory tract inflammation in grain farmers. PMID- 2305798 TI - Over-shift decrease in lung function in poultry slaughterhouse workers. PMID- 2305799 TI - Organic dust toxic syndrome among Finnish farmers. PMID- 2305800 TI - Clinical, epidemiological, and laboratory criteria for the diagnosis of bagassosis. PMID- 2305801 TI - Effects of wood dust exposure on respiratory health: cross-sectional study among farmers exposed to wood dust. PMID- 2305802 TI - Effects of wood dust exposure on respiratory health: report of an animal experiment. PMID- 2305803 TI - Occupational immunological lung disease in China. PMID- 2305805 TI - Respiratory impairment among workers in a garbage-handling plant. PMID- 2305804 TI - Effects of peat dust exposure. PMID- 2305806 TI - Celiac disease and organic dust toxic syndrome. PMID- 2305807 TI - IgG4 antibodies against pig-derived antigens. PMID- 2305808 TI - Humoral immunological profiles of a group of mill workers. PMID- 2305809 TI - Multiplane gallium tomography in assessment of occupational chest diseases. AB - Gallium-67 scintigraphy is helpful in the evaluation of inflammatory, respiratory diseases. Single-photon emission computed tomography (SPECT) provides three dimensional tomographic reconstruction of radioisotope distribution in the body. The addition of SPECT to gallium-67 scanning in 27 patients demonstrated an improvement in the sensitivity for detecting the presence and extent of interstitial occupational lung disease. This technique may provide earlier detection of parenchymal lung changes than can the chest x-ray and planar scanning in some patients with asbestosis. Findings in six patients with asbestosis are reported. PMID- 2305810 TI - Decreased lung function and exposure to diisocyanates (HDI and HDI-BT) in car repair painters: observations on re-examination 6 years after initial study. AB - Thirty-six car painters and 115 control persons participated in a follow-up investigation 6 years after the initial study, including measurement of lung function (dynamic spirometry and nitrogen washout test) and estimation of exposure to diisocyanates based on individual working routines, use of respiratory protection equipment, and measurements. The mean exposure for the car painters was 0.0015 mg/m3 hexamethylenediisocyanate (HDI) and 0.09 mg/m3 hexamethylenediisocyanate-biurettrimer (HDI-BT), but frequently there were peak exposures exceeding 2.0 mg/m3 HDI-BT for at least 30 sec. Compared with smoking controls, the smoking car painters had greater yearly reduction in FVC (95 versus 38 ml), FEV1 (61 versus 28 ml), and VC (77 versus 30 ml). The nonsmoking car painters showed no differences in lung volumes compared with their nonsmoking controls. The impairment correlated well with the frequency of high peak exposures to HDI-BT, but not with the mean exposure to diisocyanates. PMID- 2305811 TI - Fluoride in workplace air and in urine of workers concentrating fluorspar. AB - The urinary fluoride concentrations of workers exposed to calcium fluoride (CaF2) during fluorspar processing were measured. Personal dust measurement showed that the mean occupational exposure to fluoride for 12 workers in the most dusty environment was 24.3 mg/m3, which is 9.7 times the threshold limit value (TLV) of 2.5 mg/m3. Exposure was below the TLV for the remaining 23 workers. Urinary fluoride concentrations were measured pre- and postshift. The heavily exposed workers had a mean preshift concentration of 3.3 mg/liter (range 1.4-8.5 mg/liter), only slightly higher than the mean of 2.8 mg/liter (range 1.3-4.2 mg/liter) in the workers with fluoride exposure below the TLV. Four of the preshift concentrations exceeded the recommended upper limit of 4 mg/liter. The mean postshift concentration for workers exposed above the TLV was 4.4 mg/liter (range 2.4-7.1 mg/liter) and the difference between pre- and postshift concentrations was significant (p less than 0.05). Only one urinary concentration exceeded the recommended upper limit of 7 mg/liter. There was poor correlation between intensity of environmental exposure to fluorspar and postshift fluoride concentration in the urine. Eighteen workers provided a urine sample 7-14 hr after the end of a shift. The mean fluoride concentration was 4.7 mg/liter (range 2.4-11.7 mg/liter), which exceeded their postshift concentration by 0.2 mg/liter. These results indicate that the low aqueous solubility of fluorspar reduced the biologic availability of the fluoride ion but that this did not prevent excessive fluoride absorption in some workers. PMID- 2305812 TI - Methyl bromide intoxication in four field-workers during removal of soil fumigation sheets. AB - Methyl bromide is a highly toxic and penetrating compound used extensively as an insecticide for dry foodstuffs and as a soil fumigant (in greenhouses and fields) for the control of nematodes, fungi, and weeds. More than 300 cases of systemic poisoning and 60 fatalities attributable to methyl bromide have been reported [Alexeeff and Kilgore, 1983], resulting in substantial regulations concerning its handling, storage, application, and disposal. A recent exposure incident at a Connecticut nursery represents to our knowledge the first report of toxicity stemming from exposures in the field during removal of plastic sheets days after injection of methyl bromide into soil. Following removal of polyethylene sheets covering soil fumigated with methyl bromide, four field-workers developed fatigue and light-headedness and 3 workers noted progressive respiratory, gastrointestinal (GI), and neurologic symptoms. The acute systemic symptoms improved over several days, but later-onset neuropsychiatric symptoms persisted for several weeks. This incident stresses the need for improved worker education and strict adherence to safety precautions during all stages of methyl bromide fumigation and raises the possibility of an increased risk of toxicity associated with methyl bromide fumigation during a cool season. PMID- 2305813 TI - Asbestos-related pulmonary disease in boilermakers. AB - Boilermakers are skilled building tradesmen who construct, repair, and dismantle boilers. The present study reports on the evaluation of members of a Michigan boilermaker's union for the presence of signs and symptoms of chronic pulmonary disease. Study variables included standardized evaluations of chest x-ray findings, pulmonary function testing, physical examination, and respiratory symptoms. An overall participation rate of 69% was achieved. A non-participant survey identified no significant differences between participants and non participants in dyspnea, cough, age, or smoking history. Among participants with greater than 20 years experience in the trade, the mean FVC was 91% of predicted; the FEV1 was 86% of predicted; 25% showed at least a 1/0 profusion of interstitial markings on chest x-ray; 30% had bilateral pleural abnormalities; and 52% had audible inspiratory rales on physical examination. Forced vital capacity and forced expiratory volume at one second both decreased with years in the trade. Chest x-ray findings of interstitial fibrosis and pleural plaques were related to ten or more years in the trade, as were respiratory symptoms of pulmonary rales, wheeze, and dyspnea. PMID- 2305814 TI - Parkinson's disease: a case-control study of occupational and environmental risk factors. AB - We compared personal histories of 57 cases and 122 age-matched controls to identify possible environmental determinants of Parkinson's disease (PD). Odds ratios (OR) adjusted for sex, age, and smoking were computed using stepwise logistic regression. We found a statistically significant increased risk for working in orchards (OR = 3.69, p = 0.012, 95% CI = 1.34, 10.27) and a marginally significant increased risk associated with working in planer mills (OR = 4.11, p = 0.065, 95% CI = 0.91, 18.50). A Fisher's exact test of the association between PD development and (1) paraquat contact, and (2) postural tremor gave statistically significant probability estimates of 0.01 and 0.03, respectively. The relative risk of PD decreased with smoking, an inverse relationship supported by many studies. PMID- 2305815 TI - Biological monitoring of nitrous oxide exposure in surgical areas. AB - Exposure to nitrous oxide in surgical theaters was evaluated for duration, numbers, and types of surgical procedures. The concentration of the gas in the air was 92-444 ppm. Before and after the surgical sessions, samples of urine and expired air were collected from surgical theater personnel for gas determination. Nitrous oxide concentrations in urine and in expired air showed a good correlation with gas concentration in the air (r = 0.760 and r = 0.921, respectively). Moreover, a good correlation (r = 0.823) between gas concentration in urine and that in expired air was also found. A biological threshold limit value (TLV) of 20.6 micrograms/liter for urine and of 29.6 ppm for expired air was calculated, based on the limit of 50 ppm in the air proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). Other biological TLVs corresponding to higher proposed limits (200 and 500 ppm) were also calculated. PMID- 2305816 TI - Re: Drug testing: technical complications of a complex social issue. PMID- 2305817 TI - U.S. honors RNs for AIDS work. PMID- 2305818 TI - Hazardous (to the) waist. PMID- 2305819 TI - LPNs widen their role; disagreement grows. PMID- 2305820 TI - Under oath: testifying against a physician. PMID- 2305821 TI - Adoption options. PMID- 2305822 TI - Art in nursing. PMID- 2305823 TI - New hospital hazards. How to protect yourself. PMID- 2305825 TI - Infectious pneumonia in the elderly. PMID- 2305824 TI - Supporting the bereaved. PMID- 2305827 TI - Gate crashers. PMID- 2305828 TI - California jobfocus. Strike gold in California. PMID- 2305826 TI - After disaster. A crisis support team at work. PMID- 2305829 TI - Western Sunbelt jobfocus. Texas: a state of mind. PMID- 2305830 TI - Western Sunbelt jobfocus. At home in Arizona. PMID- 2305831 TI - Early morphologic changes in cat heart muscle cells after acute coronary artery occlusion. AB - The left descending coronary artery (LAD) was occluded in 16 open-chest cats for 10, 20, 40, or 60 minutes (four cats in each group). In addition, four sham operated cats served as controls. Specimens for electron microscopy were obtained from the normal and ischemic zones, guided by in vivo injection of fluorescein, and verified by blood flow measurements with microspheres. The ultrastructure of 2,400 heart muscle cells and nuclei was studied. Fractional volumes of main cell components, mitochondrial surface density, and mitochondrial surface: volume ratio were calculated in 480 micrographs. After 10 minutes of ischemia we observed signs of sarcolemmal fragility, mitochondrial swelling, and lipid droplet accumulation. After 20 minutes of ischemia sarcolemmal fragmentation, chromatin clumping or margination and a maximal cytoplasmic edema were evident. The fractional volume of mitochondria was equally increased in ischemic zones of all groups. In both normal and ischemic zones there was a tendency toward smaller fractional volumes of lipid droplets during ischemia. In the normal zone there was mild cytoplasmic edema and slight mitochondrial swelling 10 minutes after occlusion as compared with the sham group. The present study demonstrates that a large proportion of cardiac myocytes undergoes severe damage within 20 minutes of coronary occlusion. PMID- 2305832 TI - Chromogranin A and B gene expression in carcinomas of the breast. Correlation of immunocytochemical, immunoblot, and hybridization analyses. AB - Chromogranins (Cg) are regarded as specific neuroendocrine (NE) markers in cells and tumors. Expression of CgA and CgB genes has been demonstrated by correlative immunocytochemical, immunoblotting, in situ hybridization, and Northern blot procedures in seven argyrophilic breast carcinomas, while eight control cases of ductal carcinomas, not otherwise specified, were negative. A high degree of correlation was observed between the various techniques revealing CgA and/or CgB gene expression at different levels; minor discrepancies might be related to tumor heterogeneity or to technical factors. The present study, confirming previous investigations, establishes NE differentiation in a group of human breast cancers. The identification of this type of tumors, especially by testing chromogranin(s) production, appears to be of both biologic and clinical interest. PMID- 2305833 TI - IL-2 mRNA expression in Tac-positive malignant lymphomas. AB - Expression of the IL-2 receptor (Tac antigen/CD25) is documented in malignant lymphomas. Because IL-2 is a major lymphocyte growth factor, an IL-2-dependent growth could be involved in the proliferation of Tac-positive lymphomas. Indeed such a mechanism has been demonstrated experimentally for the growth of T-cell lines. To investigate this point in human lymphomas, we used in situ hybridization to analyze the expression of the IL-2 gene in 20 non-Hodgkin's lymphomas, among which 12 expressed the IL-2 receptor. Nine of these were anaplastic large cell lymphomas expressing the Ki-1-related antigen. We here show that IL-2-producing cells are present in all the lymphomas we analyzed. As a mean, there is no significant difference in the percentage of IL-2-producing cells between Tac-positive and -negative lymphomas. However, the level of IL-2 production is highly heterogeneous in both groups, and the highest density of IL 2-producing cells was observed in 2 Tac-positive lymphomas. Simultaneous detection of cellular antigens and of IL-2 mRNA demonstrates that IL-2 is produced by reactive T cells rather than by tumor cells. These results suggest that if IL-2 is involved in the growth of Tac-positive lymphomas, it acts as a paracrine, rather than an autocrine, factor. PMID- 2305835 TI - ME1. A monoclonal antibody that distinguishes epithelial-type malignant mesothelioma from pulmonary adenocarcinoma and extrapulmonary malignancies. AB - ME1 is a monoclonal antibody reactive in frozen tissue sections with normal mesothelial cells and malignant mesotheliomas. In this immunoperoxidase study, ME1 reacted with all 40 epithelial type malignant mesotheliomas. Fifty percent or more of the mesothelioma cells were stained in all cases and the staining intensity was strong in 32 and moderate in eight. In contrast, all 19 well- and moderately differentiated pulmonary adenocarcinomas were completely negative, and of the total 88 non-mesotheliomatous malignancies studied, staining comparable to the mesotheliomas was seen in only 6 tumors (2 pulmonary adenocarcinomas, 2 adenocarcinomas of the breast, 1 adenocarcinoma of the pancreas, and 1 melanoma), although limited, weaker staining was seen in additional cases. Five of the six strongly to moderately positive nonmesotheliomatous tumors had immunoreactivity for complementary immunoreactants (CEA, Leu-M1, S-100 protein, HMB-45). Our results with ME1, the first monoclonal antibody that recognizes malignant mesothelial cells, provides a basis for using this reagent in the differential diagnosis of tumors of the pleura and peritoneum. PMID- 2305834 TI - Matrix vesicle biogenesis in vitro by rachitic and normal rat chondrocytes. AB - Calcifying matrix vesicles (MVs) are released from chondrocytes and osteoblasts in monolayer culture. In the present studies, we tested the ability of rachitic versus normal rat growth plate chondrocytes in micromass or monolayer primary cultures to produce MVs. Unlike earlier reports of in vitro MV biogenesis by chicken chondrocytes in which most MVs were released into the medium, we found that most of the released rat matrix vesicles were entrapped in a newly formed cartilaginous matrix enveloping the cells. These matrix-associated MVs could be isolated by mild collagenase treatment and concentrated by differential centrifugation. Vesicle production slowed in the older 2- to 4-week-old cultures and, unlike vesicle release from cultured chicken chondrocytes, active vesicle production did not show a second burst of activity at 3 to 4 weeks. Alkaline phosphatase (ALP) activity diminished with time in culture in cells and matrix vesicles, suggesting a decrease in differentiative expression. Protein profiles on SDS polyacrylamide gels of native matrix vesicles and culture-derived MVs from rachitic and normal cells were quite similar and showed a typical simplified protein pattern as compared to chondrocyte plasma membrane proteins. There were distinctive proteins migrating at 130, 80 to 95, 66, 43, 20, and 14 kd. Culture derived MVs showed vigorous in vitro calcifying activity that was ALP related. We conclude that 1) rachitic chondrocytes are essentially normal in their matrix vesicle production; 2) matrix entrapment of MVs is a characteristic of rat chondrocyte cultures; and 3) culture-produced MVs are similar to native MVs in protein profile and calcifiability, and thus can be studied as a model for normal MV composition and calcification. PMID- 2305836 TI - The evolution of benign arterionephrosclerosis from age 6 to 70 years. AB - Arterionephrosclerosis is diagnosed at autopsy by assessing the severity and extent of certain structural features in the renal cortical arteries seen in tissue sections. These features are characterized by fibrotic intimal thickening and medial shrinkage, a progressive change from the youthful muscular pattern to the elderly sclerotic pattern. Intimal fibrosis can be quantified by expressing intimal thickness as a percentage of the arterial outer diameter (% OD). The magnitude of arterionephrosclerosis, found by averaging the measures of intimal fibrosis seen in a kidney, can be calculated from age and mean blood pressure, using a standard prediction function. This function is a quantitative statement of a fundamentally important principle: just as blood pressure is a continuous variable that can range from low to high levels, arterionephrosclerosis is also a continuous variable that can take any degree of abnormality of arterial structure from minimal to maximal. Furthermore, a correspondence exists between the two quantities so that each can be calculated from the other. In this study, a correlation of 0.966 was found between the observed and the calculated magnitudes of arterionephrosclerosis over 10-year age groups from 25 to 34 years to 65 to 74 years, using group average data within age groups. For individuals, however, the correlations between observed and calculated magnitudes of arterionephrosclerosis were about 0.6 in a former study of elderly subjects and about 0.1 in the subjects aged 6 to 27 years in this study. The average growth rate of arterionephrosclerosis was found to be about 0.25 %OD per year from ages 15 to 54 years, and about 0.13 %OD per year from ages 55 to 70 years; the growth rate did not increase in the oldest age groups when blood pressure averaged higher than blood pressure in more youthful subjects. These and other findings are consistent with the view that the reason a correlation exists between blood pressure and arterionephrosclerosis could be because the magnitude of arterionephrosclerosis is one of the determinants that sets the level of blood pressure. From this perspective, each individual can be viewed as having other determinants of blood pressure, methodologic or biologic, which add to or subtract from the values set by age and arterionephrosclerosis. When subjects are pooled into groups, so that individual determinants balance out, the group average levels of mean blood pressure could be interpreted as reflecting little other than the magnitude of arterionephrosclerosis at each specific age. PMID- 2305837 TI - Age-related accumulation of amyloid inclusions in adrenal cortical cells. AB - Cytoplasmic fine fibrillar inclusions with properties of amyloid occur as neurofibrillary tangles in the brain and in the aging choroid plexus. In the present study we show that inclusions, similar but not identical to those in the choroid plexus, are common in the adrenal cortex of elderly persons. The inclusions consist of aggregates of parallel fine fibrils, often in contact with lipid droplets and partially limited by a membrane. The inclusions have affinity for Congo red and exhibit a bright green birefringence after this staining. Therefore, the inclusions can be regarded as a form of senile amyloid. PMID- 2305839 TI - Therapeutic case advocacy: a model for interagency collaboration in serving emotionally disturbed children and their families. AB - A model for the creation of a system of care for emotionally handicapped children and their families is presented. The model delineates a framework for modifying environments and for identifying the clinical skills necessary to do so. Coordination of the efforts of both formal organizations and natural support systems is seen as an essential component of the proposed system. PMID- 2305838 TI - Patterns of MHC antigenic modulation in cyclosporine-induced autoimmunity. Implications for pathogenesis. AB - To explore the role of aberrant MHC expression in the pathogenesis of cyclosporine-induced autoimmunity (CSIA), we examined the patterns of major histocompatibility complex (MHC) class I and II antigenic modulation during disease induction and the relationship between MHC modulation and tissue injury. Disease was induced consistently in rats but never in mice. Unlike rats, mice were resistant to downmodulation by cyclosporine of class II antigen expression in the thymic medulla. In rats with CSIA, MHC class I and II antigen expression was induced on all target epithelia, frequently before mononuclear infiltration or tissue injury, consistent with a role for MHC antigens in selecting cells for injury. Much increased numbers of strongly class II-positive interstitial dendritic cells were present throughout the body, even in tissues not involved by CSIA. Thus, class II expression alone is insufficient to lead to cell injury in CSIA. PMID- 2305840 TI - Countertransference in working with victims of political repression. AB - The countertransferential reactions of psychotherapists working in a threatening environment with victims of political repression are described. Via case studies based on clinical consultation and direct testimony, this paper examines the effects on Chilean therapists living and working in that country. It is suggested that these clinical observations may have application to therapeutic work with victims in other stressful settings. PMID- 2305841 TI - Group treatment of exiled survivors of torture. AB - A model for time-limited group treatment of exiled survivors of torture is presented and the importance of placing such traumatic experiences in a sociopolitical context is emphasized. The model is illustrated by descriptions of work with a group made up of Central and South American refugees. Therapeutic techniques are proposed that focus on symptoms of torture-related post-traumatic stress disorder, allowing group members to attain gradual psychological reorganization. PMID- 2305842 TI - The psychological effects of political repression on Chilean exiles in the U.S. AB - Interviews with 32 Chilean refugees elicited descriptive findings on the effects of detention and torture and subsequent exile in the U.S. It is suggested that exile for this group constitutes a continuation rather than a cessation of their suffering. Marital problems, economic hardship, and loneliness are recounted by the adults, while teachers and parents report adjustment and behavioral difficulties among the children. The influence of sociopolitical factors on these outcomes is discussed. PMID- 2305843 TI - The new allegiance to interdisciplinary work: true or false? PMID- 2305844 TI - Buffalo Creek survivors in the second decade: stability of stress symptoms. AB - A follow-up study of 120 adult survivors of the Buffalo Creek dam collapse of 1972 showed group changes 14 years after the event. Decreased symptoms were noted in all areas, although significant psychopathology remained in about one-quarter of the survivors. A small group with delayed onset of symptoms was identified. PMID- 2305845 TI - Physical and sexual abuse in adolescent girls with borderline personality disorder. AB - Recent investigations suggest that a history of childhood sexual abuse may be associated with borderline personality disorder. This study compares a group of female adolescents diagnosed as borderline with a control group for history of physical and sexual abuse. History of both forms of abuse, particularly sexual, distinguishes the two groups. Results point to the impact of repeated trauma on character structure, cognitive functioning, and Axis II symptomatology. PMID- 2305846 TI - Factors associated with academic achievement in children following parental separation. AB - Elementary school children who maintained their academic performance levels following separation of their parents were compared to those whose levels declined. Although no single measure could accurately predict children's academic adjustment, those who maintained performance levels spent significantly more time with both parents. PMID- 2305847 TI - Sense of competence, time perspective, and state-anxiety of separated versus divorced mothers. AB - Separated and divorced mothers, with median separation times of four and 22 months, respectively, were compared on sense of competence, time perspective, and state-anxiety. Divorced mothers showed less defensiveness, in that their self esteem ratings were more congruent with their self-efficacy and anxiety ratings. They also showed more positive time perspective, indicating greater optimism and suggesting a process of positive emotional transition. PMID- 2305848 TI - Men as elder caregivers: a response to changing families. AB - Results are presented from a study that examined the relationship between gender orientation and the unique stresses and gratifications for men who are engaged in caregiving tasks traditionally performed by women. The men report having found emotional gratification an important motivating factor, and they tended to ascribe to themselves many affective traits usually associated with the female role. PMID- 2305849 TI - Determinants of family treatment choice and satisfaction in psychiatric emergencies. AB - The experiences of 60 families in psychiatric emergencies involving a mentally ill relative are studied. Results indicate that family choices of more restrictive treatment are influenced by patient treatment histories, and that family dissatisfaction with service response is best predicted by patient symptomatology and resistance, and by family attitudes toward treatment. PMID- 2305850 TI - Acoustic neuroma: clinical aspects, audiovestibular assessment, diagnostic delay, and growth rate. AB - The diagnostic findings in 300 patients with acoustic neuromas are reported. Because of a centralized treatment of acoustic neuromas, we have a uniform diagnostic work-up of all patients, which enables us to make a nonselected comparison of the diagnostic efficiency of the various tests. In patients with hearing better than 80 dB, a normal auditory brainstem response, the presence of recruitment, and normal caloric reaction, the presence of a tumor can be excluded. In patients with poor hearing, tomography is necessary if one does not prefer to perform CT directly. If CT, even with contrast enhancement, is negative, we continue to perform air CT. Only then do we know whether or not the patient has a tumor. Magnetic resonance imaging has not been available to us, but with this diagnostic modality even intrameatal tumors are visualized. However, with the present economy involved with magnetic resonance imaging it is not realistic at the present time to use this way of imaging as a screening procedure. In spite of an intensive campaign for making early diagnosis of acoustic neuromas, our attempts have not been successful, since we have even more tumors measuring over 40 mm in diameter among the latest 100 patients than among the first one hundred. Both patients and physicians (otologists) to some extent are still ignoring the possible significance of a unilateral, progressive, sensorineural hearing impairment. Guidelines for improving this situation are given. Twenty-one patients were followed for an average of 4 years, repeated CT scans were performed, and the tumor appeared to be progressing to a size requiring surgical intervention in only three of these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305851 TI - Adenomatous tumors of the middle ear and mastoid. AB - Adenomatous tumors of the middle ear and mastoid have been called adenoma or adenocarcinoma. The clinical and pathologic distinction between the two has been difficult. The resultant pathologic ambiguity makes it difficult to decide whether conservative or radical management is appropriate. The Otologic Medical Group's (OMG) experience with glandular tumors of the middle ear and mastoid over the past 27 years was reviewed. Thirteen cases were found and analyzed with respect to signs and symptoms at presentation. Extensive histopathologic review with light and electron microscopy was performed on tumor specimens. Two distinctive histopathologic and clinical patterns were identified. The mixed type of tumor was always confined to the middle ear and mastoid, was commonly misdiagnosed as chronic otitis media, and rarely demonstrated otic capsule or facial nerve involvement. The papillary pattern always had extension to the petrous apex and frequently involved the middle and/or posterior cranial fossa. Papillary tumors were more frequent in females and usually involved the facial nerve. On the basis of the findings in this review as well as information from the literature, we have come to the following conclusions: 1. The correct general pathologic heading be Adenomatous Tumors of the Middle ear and Mastoid with each tumor then being subclassified into Mixed or Papillary tumor and adenocarcinoma when warranted by histology. 2. There is a high rate of local recurrence. 3. Long term follow-up (at least 10 years) for all adenomatous tumors is necessary. 4. Primary surgical treatment is required. PMID- 2305852 TI - Type II collagen-induced inner ear disease: critical evaluation of the guinea pig model. AB - Guinea pigs systematically challenged with type II collagen were examined electrophysiologically, histologically, and immunologically for inner ear lesions. Some functional, morphologic, and immunologic changes could be demonstrated. Evidence of possible immunoglobulin deposition in the basilar membrane, the perivascular region, as well as in other inner ear tissue were present. Immunologic and histopathologic simulations to inner ear diseases in humans and to the inner ear antigen-induced animal model were found. The results are discussed in light of the original model introduced by Yoo et al and the reexamination findings reported by Harris et al. The discrepancies in the results are argued, and the impact of this experimental model on human autoimmune inner ear disease is analysed. PMID- 2305853 TI - Type II collagen distribution in the monkey ear. AB - A possible role for type II collagen autoimmunity in the pathogenesis of Meniere's disease and otosclerosis was recently suggested by studies demonstrating anti-type II collagen antibody in the serum of humans with these disorders and by the induction of similar lesions in animals immunized with type II collagen. In light of these findings, we studied the anatomic distribution of type II collagen in the nonhuman primate ear by immunohistochemical techniques using defined monoclonal antibodies to type II collagen. Type II collagen was observed in the cartilage plate of the auricle and external auditory meatus, tympanic annulus, lamina propria of tympanic membrane (pars tensa), interossicular joints, stapes footplate, eustachian tube cartilage, enchondral layer and globuli interossei of the otic capsule, Rosenthal canal, cribriform base, osseous spiral lamina, spiral ligament, limbus, tectorial membrane, semicircular canal membrane and subepithelial layer of the ampullary crista, utricular and saccular maculae, and the endolymphatic duct and proximal part of the sac. Thus, type II collagen should be considered an important component of ear tissue. PMID- 2305855 TI - Significance of prolonged conduction latency in Bell's palsy. PMID- 2305856 TI - Subject: atypical Bell's palsy. PMID- 2305854 TI - The occlusion effect created by custom canal hearing aids. AB - There has recently been a dramatic increase in the demand for custom canal hearing aids. One of the significant limitations sometimes created by these instruments is the increased sensitivity to bone-conducted stimuli known as the occlusion effect. A large occlusion effect is often cited as the reason for rejection of these devices. This investigation tested a method of measuring the occlusion effect through bone-conducted speech reception thresholds (SRTs). The results indicated that the bone conducted SRT procedure is sensitive enough to differentiate between the occlusion effect created by shell earmolds versus canal hearing aids. PMID- 2305857 TI - Progressive oral puckering. PMID- 2305858 TI - Recurrent alternating facial palsy. PMID- 2305860 TI - Questions regarding Bell's palsy: viral prodrome, type of onset of Bell's virus cholesteatoma. PMID- 2305859 TI - Nonsurgical management of Frey's syndrome. PMID- 2305861 TI - Radiation injury to the temporal bone. AB - Osteoradionecrosis of the temporal bone is an unusual sequela of radiation therapy to the head and neck. Symptoms occur many years after the radiation is administered, and progression of the disease is insidious. Hearing loss (sensorineural, conductive, or mixed), otalgia, otorrhea, and even gross tissue extrusion herald this condition. Later, intracranial complications such as meningitis, temporal lobe or cerebellar abscess, and cranial neuropathies may occur. Reported here are five cases of this rare malady representing varying degrees of the disease process. They include a case of radiation-induced necrosis of the tympanic ring with persistent squamous debris in the external auditory canal and middle ear. Another case demonstrates the progression of radiation otitis media to mastoiditis with bony sequestration. Further progression of the disease process is seen in a third case that evolved into multiple cranial neuropathies from skull base destruction. Treatment includes systemic antibiotics, local wound care, and debridement in cases of localized tissue involvement. More extensive debridement with removal of sequestrations, abscess drainage, reconstruction with vascularized tissue from regional flaps, and mastoid obliteration may be warranted for severe cases. Hyperbaric oxygen therapy has provided limited benefit. PMID- 2305862 TI - Homograft tympanoplasty: a long-term review of 477 ears. AB - Homograft materials have been employed to reconstruct the tympanic membrane and ossicular chain since the mid-1960s. Although the use of homograft materials remains somewhat controversial, this technique has been shown to provide excellent long-term results, both anatomically and functionally. This study reports on the long-term results of 477 ears undergoing homograft tympanoplasty and the modification of previously reported surgical techniques. PMID- 2305863 TI - The operative report. PMID- 2305864 TI - Age, anatomic site, and the replication and differentiation of adipocyte precursors. AB - The effects of donor age and anatomic site on cellular replication and differentiation were studied in adipocyte precursors cloned from epididymal and perirenal depots of young, middle-aged, and senescent rats. As animals aged from 3 to 29 mo, there was a progressive reduction in the proportion of cells capable of extensive replication in both depots. An inverse relation between clonal capacity for replication and differentiation was found. This relation was affected by donor site but not age. Aging was, however, associated with a reduction in the frequency of clones capable of full differentiation into cells with single, large, central lipid inclusions. Hence, age and donor site may affect adipocyte precursor replication and differentiation by different mechanisms. PMID- 2305865 TI - Protein kinase C mediates cholinergically regulated protein phosphorylation in a Cl(-)-secreting epithelium. AB - T84 cell monolayers were used to study the cholinergic regulation of protein phosphorylation in epithelial cells. When T84 cell monolayers are labeled with 32Pi and stimulated with carbachol, six proteins exhibit altered phosphorylation. The most prominent response is a fivefold increase in labeling of p83, an acidic protein of Mr 83,000. Increasing labeling of p83 parallels stimulated secretion with respect to the onset of agonist action, agonist potency, and antagonism by atropine. However, the p83 and secretory responses differ in that the p83 response is more sustained. When T84 cell fractions are incubated with [gamma 32P]ATP, Ca2(+)-phospholipid stimulates p83 labeling. Phosphorylation of p83 also occurs when a T84 cell extract is incubated with purified protein kinase C and when intact cells are exposed to phorbol myristate acetate. p83 does not become phosphorylated in cell fractions incubated with adenosine 3',5'-cyclic monophosphate (cAMP) or in monolayers stimulated with agonists acting via cAMP. Thus carbachol stimulates the phosphorylation of an endogenous substrate for protein kinase C in T84 cells. The duration of this phosphorylation response suggests that protein kinase C may mediate a sustained response to carbachol, possibly acting to limit the duration of stimulated secretion. PMID- 2305866 TI - Whole cell recording of sugar-induced currents in LLC-PK1 cells. AB - Gigaohm-seal whole cell recording techniques were used to monitor function of the Na(+)-coupled sugar transport system in LLC-PK1 cells. The currents coupled to sugar transport were identified as those that are induced by the presence of 10 mM alpha-methylglucoside (AMG) in either the extracellular or intracellular compartment and were inhibited by addition of 320-800 microM phlorizin to the extracellular bathing medium. The sugar-induced currents are small, 15-20 pA, but of the expected magnitude as determined from the known kinetic parameters for Na(+)-coupled sugar transport in LLC-PK1 cells. The phlorizin-sensitive currents are Na+ dependent and can be studied under conditions in which the net Na+ and sugar flux (and consequently the Na+ electrical current) is in either the inward or outward direction. The reversal potential of the sugar-induced currents measured under conditions with high Na+ and AMG concentrations inside the cell is close to values predicted from thermodynamic principles, assuming a coupling stoichiometry of 2 Na+: 1 sugar for the transport system. The reversal potential of the sugar-induced currents with high extracellular Na+ and AMG is not equal to the predicted value, but it is of the polarity expected for inward-imposed solute gradients. Reasons for the observed discrepancy between observed and calculated values are discussed. PMID- 2305867 TI - Evidence for chloride secretion in the intestine of the winter flounder. AB - The effects of a novel antisecretory peptide (CAP) isolated from porcine heart and vasoactive intestinal peptide (VIP) on ion transport were investigated in the winter flounder intestine. Partially purified CAP caused a two- to sixfold increase in the serosa-negative short-circuit current (Isc) with no significant change in tissue conductance. CAP significantly inhibited the serosal-to-mucosal (S-M) unidirectional Cl flux without affecting either Na or Rb transepithelial fluxes. The Isc after the addition of CAP was completely inhibited by 0.1 microM atriopeptin III (AP-3), 10 microM bumetanide, and 100 microM 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP). In contrast to the effects of CAP on Isc, VIP decreased the serosa-negative Isc by 40-60%. VIP stimulated the S-M unidirectional Cl flux without affecting transepithelial Na transport. When food was present in the intestine, the basal Isc was occasionally found to be serosa positive, ranging between 10 and 40 microA/cm2. Treatment of tissues exhibiting serosa-positive currents with VIP resulted in an increase (positive direction) in Isc. Addition of CAP to tissues with a serosa-positive Isc or to tissues pretreated with VIP resulted in a serosa-negative Isc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305868 TI - Adenine nucleotide degradation in slow-twitch red muscle. AB - The catabolism of adenine nucleotides (AdN) in rat soleus muscle (predominantly slow twitch) is very different from that in fast-twitch muscle. AMP deaminase is highly inhibited during brief (3 min) intense (120 tetani/min) in situ stimulation, resulting in little inosine 5'-monophosphate (IMP) accumulation (0.21 mumol/g). Even with ligation of the femoral artery during the same brief intense contraction conditions there is surprisingly little increase in IMP (0.37 mumol/g), although AdN depletion is evident (-1.30 mumol/g). We have tested the hypothesis that accumulation of purine nucleosides and bases accounts for the AdN depletion by measuring purine degradation products using high-performance liquid chromatography. There was no stoichiometric accumulation of purine degradation products to account for the observed AdN depletion even though metabolite recovery was essentially quantitative. We hypothesis that under these conditions AdN are converted to a form different from purine nucleoside and base degradation products. In contrast to the inhibition of AMP deamination seen during brief ischemia, slow-twitch muscle depletes a substantial fraction (28%) of muscle AdN (1.75 mumol/g) that can be accounted for stoichiometrically as purine degradation products during an extended 10-min ischemic period of mild (12 tetani/min) contraction conditions. IMP accumulation (1 mumol/g) is most prominent with inosine, accounting for 23% (0.4 mumol/g) of the depleted AdN, showing that slow twitch red muscle is capable of both AMP deamination and the subsequent production of purine nucleosides during an extended period of ischemic contractions. The present results indicate that AdN metabolism in the soleus muscle is complex, yielding expected degradation products or a loss of total purines, depending on contraction conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305869 TI - Vasoactive intestinal peptide stimulates active K+ transport and Na(+)-K(+)-Cl- cotransport in HT-29 cells. AB - Regulation of active K+ influx and Na(+)-K(+)-Cl- cotransport activity in HT-29 cells by vasoactive intestinal peptide (VIP) was investigated. Both active K+ influx, defined as the ouabain-sensitive component, and Na(+)-K(+)-Cl- cotransport, defined as the ouabain-resistant bumetanide-sensitive component, of total K+ uptake were increased by VIP. VIP increased the maximum velocity (Vmax) values for both components with no change in apparent Michaelis constant (Km) values. Three lines of evidence support the role of adenosine 3',5'-cyclic monophosphate (cAMP) as a mediator of the VIP effects. 1) The rank order potencies of VIP and peptide histidineisoleucineamide (PHI) in binding and cAMP production (J. T. Turner, S. B. Jones, and D. B. Bylund, Peptides Fayetteville 7: 849, 1986) and K+ uptake were consistent; 2) alpha 2-adrenergic agonists inhibited both VIP-stimulated cAMP production (J. T. Turner, C. Ray-Prenger, and D. B. Bylund, Mol. Pharmacol. 28: 422, 1985) and K+ uptake; and 3) forskolin, but not dideoxyforskolin, mimicked the effects of VIP on K+ uptake. Because amiloride blocked the VIP-stimulated active K+ component, the VIP effects on active K+ influx may be secondary to a Na(+)-H+ antiporter-mediated increase in cellular Na+ content. Additional experiments indicated that pretreatment of cells with a protein kinase C activator, previously shown to decrease basal Na(+)-K(+)-Cl- cotransport activity and the apparent number of cotransporters in HT-29 cells (C. C. Franklin, J. T. Turner, and H. D. Kim, J. Biol. Chem. 264: 6667, 1989), did not change the magnitude of response of the remaining cotransporters after adenylate cyclase activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305870 TI - Temperature dependence of myofilament Ca sensitivity of rat, guinea pig, and frog ventricular muscle. AB - Cooling the superfusate of intact ventricular muscle, from 30 degrees C to below 4 degrees C in less than 2 s, leads to contractures thought to reflect the amount of Ca available for release from the sarcoplasmic reticulum (SR). On rewarming, tension transiently increases in guinea pig and rat ventricular muscle. It has been proposed that this rewarming tension spike reflects changes in myofilament Ca sensitivity and maximum Ca-activated force (Cmax) associated with rewarming. There are differences in intracellular Ca regulation among cardiac muscle preparations. Some characteristics of rapid-cooling contractures (e.g., the magnitude of the rewarming spike) also differ between species. Therefore, the Ca sensitivity of skinned ventricular muscle from the rat, guinea pig, and frog was determined at 29 (22 degrees C for frog ventricular preparations), 8, and 1 degrees C. The results show that cooling rat and guinea pig ventricular muscle from 29 to 1 degrees C shifts the pCa vs. tension relationship toward higher [Ca2+] by 0.65 and 0.55 pCa units, respectively. Cooling to 1 degrees C also reduced Cmax to 3.3 and 7.8% of that at 29 degrees C in rat and guinea pig ventricular muscle, respectively. Similar results were found for frog ventricular muscle, in which cooling from 22 to 1 degrees C reduced Ca sensitivity by 0.6 pCa units and Cmax to 45.7% of its value at 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305871 TI - Modification of temperature dependence of myofilament Ca sensitivity by troponin C replacement. AB - The Ca sensitivity of chemically skinned right ventricular trabeculae from the rat heart was determined at 22 and 8 degrees C. Endogenous troponin C (TnC) was then extracted with EDTA and replaced with either bovine cardiac TnC or rabbit fast-twitch skeletal TnC. The temperature dependence of myofilament Ca sensitivity was then reevaluated. Cooling native cardiac tissue from 22 to 8 degrees C reduced the pCa (-log10 [Ca2+]), generating half-maximal tension (K1/2) from 5.20 +/- 0.07 to 4.89 +/- 0.08 (SD, n = 14), and also reduced maximum Ca activated force to 33 +/- 6% of its value at 22 degrees C. After extraction of endogenous TnC and reconstitution with cardiac TnC, cooling from 22 to 8 degrees C caused a similar shift in mean K1/2 from 4.93 +/- 0.08 to 4.69 +/- 0.06 (n = 7). When skeletal TnC was reconstituted into TnC-extracted ventricular fibers, cooling from 22 to 8 degrees C led to a much smaller mean shift in K1/2 from 4.88 +/- 0.07 to 4.78 +/- 0.04 (n = 7). The results show that the magnitude of the cooling-induced shift in myofilament Ca sensitivity observed in the native state (or after reconstitution with cardiac TnC) is significantly reduced if the fiber is reconstituted with skeletal TnC (P less than 0.001). This indicates that the temperature dependence of myofilament Ca sensitivity of cardiac muscle can be modified by incorporation of skeletal TnC. Thus Ca binding to TnC plays an important role in determining the temperature dependence of myofilament Ca sensitivity. PMID- 2305872 TI - Stimulation of glucose transport in Clone 9 cells by exposure to alkaline pH. AB - Incubation of a rat liver cell line (Clone 9) for 2 h at pH 8.5 was found to result in a profound (5- to 8-fold) stimulation of cytochalasin B-inhibitable glucose transport. The enhancement of glucose transport after exposure to elevated external pH (achieved by lowering the CO2 tension in a bicarbonate containing medium) was demonstrable within 15 min, was half-maximal at pH 8.0, and was near-maximal at pH 8.6. Intracellular pH rose linearly with incremental changes in external pH, from pH 7.45 to 8.6 with a slope of 0.6. The increase in transport activity in response to incubation at alkaline pH was accompanied by a parallel increase in lactate production and persisted for more than an hour after external pH was restored to normal. During the latter period, intracellular glucose concentration (less than 10% of that of the external medium under control conditions) increased greater than 10-fold to approximate that in the extracellular medium. Incubation of these cells at pH 8.5 for 2 h resulted in a complete resistance of cell ATP levels to challenge with 5 mM cyanide, suggesting that the adaptive facilitation of glucose transport was of sufficient magnitude to permit a marked stimulation of glycolytic ATP synthesis on inhibition of oxidative phosphorylation. The enhancement of glucose transport was attributable to an increase in the maximum velocity (Vmax) rather than to any change in the Michaelis constant (Km) for transport and was not prevented by cycloheximide. It is concluded that the marked stimulation of glucose transport resulting from exposure of these "low-glucose" cells to alkaline pH reflects either an increase in the abundance of functional glucose transporters in the plasma membrane or an increase in their catalytic turnover rate. PMID- 2305873 TI - Intracellular pH and membrane potassium conductance in rabbit distal colon. AB - Intracellular pH (pHc) was measured in the short-circuited epithelium of rabbit distal colon using H(+)-selective microelectrodes. pHc was 6.91 +/- 0.02 (SE) when the bath pH was 7.4. Intracellular HCO3- activity (acHCO3-) was estimated from these measurements to be 8 +/- 0 mM. When we replaced all Cl- in the tissue bathing solutions with the impermeant anion gluconate, pHc rose to 7.44 +/- 0.08 and acHCO3- increased to 30 +/- 6 mM. These results demonstrate that this tissue contains a Cl(-)-HCO3- exchange mechanism. During the Cl- replacement the apical membrane electrical potential difference hyperpolarized from -55 +/- 1 to -74 +/- 3 mV, suggesting that membrane ionic conductance had changed. Elevation of either the apical or basolateral membrane bathing solution K+ concentration produced a greater depolarization of membrane potential during Cl- replacement than when tissues were bathed in normal electrolyte solutions. In additional experiments, pHc was raised by lowering the bath CO2 concentration while the bath Cl- concentration was kept normal. Under these conditions, membrane potential hyperpolarized and was more sensitive to the elevation of bath K+ concentration than when pHc was normal. These results suggest that membrane K+ conductance in this tissue is increased by intracellular alkalinization. PMID- 2305874 TI - Smooth muscle energetics and theories of cross-bridge regulation. AB - The energetics of smooth muscle is characterized by low tension cost (rate of ATP utilization per isometric force/cross-section area), ranging from 100- to 500 fold less than skeletal muscle. The efficiency (ATP usage per work) of smooth muscle, although less well documented, is also somewhat (4-fold) less than skeletal muscle. Another well-known characteristic of smooth muscle is the linear relation between the steady-state of ATP utilization (JATP) and isometric force. Recently, Murphy and colleagues [C.-M. Hai and R. A. Murphy. Am. J. Physiol. 254 (Cell Physiol. 23) C99-C106, 1988] have put forth a kinetic model of cross-bridge regulation that predicts the time course of stress and myosin light chain phosphorylation (MLC-Pi). The energetics consequences of this model, in brief, are that the low tension cost is partly attributed to a slow detachment rate of the myosin cross bridge when dephosphorylated when attached to actin ("latch state"), whereas the lower efficiency is ascribed to a high rate of myosin phosphorylation-dephosphorylation inherent to a fit of data to this kinetic scheme. This latter corollary is somewhat controversial in light of current interpretations of smooth muscle energetics data. Using SCoP software (National Biomedical Simulation Resource, Duke University), we tested this model in terms of fitting existing data with respect to 1) is a high myosin-dephosphorylation adenosine triphosphatase (ATPase) necessary to fit the available data on the time course of stress and MLC-Pi?; and 2) can this model predict the observed linear relation between the steady-state rate of ATP hydrolysis (JATP) and isometric force?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305875 TI - Effects of age and level of physical activity on plasma norepinephrine kinetics. AB - We examined the effects of age and physical activity on plasma norepinephrine (NE) kinetics in active and inactive older and younger men. NE kinetics were estimated by calculation of the rates of NE appearance and clearance during infusion of tritiated norepinephrine [( 3H]-NE). Older active men had the highest level of plasma NE (pg/ml) and NE appearance (microgram.min-1.FFW-1, where FFW is fat-free weight) relative to younger men and inactive older men. NE clearance (l.min-1.FFW-1) was not influenced by age or physical activity. No significant associations were noted between percent body fat, supine blood pressure with resting levels of NE, NE appearance, and NE clearance. We concluded that 1) chronic participation in physical activity by older men, but not younger men, is associated with higher resting levels of plasma NE and NE appearance and 2) the degree of adiposity does not influence plasma NE kinetics in healthy younger and older men. The level of physical activity is an influencing factor on plasma NE and NE appearance into circulation in healthy older men. PMID- 2305876 TI - Effects of epidermal growth factor on bone formation and resorption in vivo. AB - The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double [3H]proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g 1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at physiological doses induces distinct effects on endosteal and periosteal bone formation and that the effects are dependent on EGF dosage and duration of treatment. This study indicates that EGF at physiological dosage stimulates periosteal bone formation and increases endosteal bone resorption in the growing mouse. PMID- 2305877 TI - Effect of parathyroid hormone-like peptides on 25-hydroxyvitamin D-1 alpha hydroxylase activity in rodents. AB - The role of vitamin D metabolism in the humoral hypercalcemia of malignancy syndrome (HHM) is unclear. We studied in vivo and in vitro effects of synthetic parathyroid hormone-like peptides (PTH-LPs) on rodent renal 25-OHD-1 alpha hydroxylase activity. Infusion of mice with PTH-LP-(1-36) at 10 pmol/h for 12 and 24 h showed significant (429 +/- 139% and 937 +/- 413%, respectively) stimulation of control enzyme activity. Infusion for 36 h demonstrated diminution of activity to levels nearer to the unstimulated state (228 +/- 36% of control). In that maximal activity was observed after 24 h of infusion, we examined 1 alpha hydroxylase activity after variable dosages of PTH-LP-(1-36) at this time point. Animals infused with PTH-LP-(1-36) at dosages of 2.5, 10, and 30 pmol/h for 24 h demonstrated 1 alpha-hydroxylase activities of 0.71 +/- 0.12, 4.74 +/- 2.09, and 9.91 +/- 1.01 ng.mg protein-1.20 min-1 (means +/- SD), respectively, all significantly greater than control activity (0.51 +/- 0.20 ng.mg protein-1.20 min 1). PTH-LP-(1-36) and PTH-LP-(1-74) were comparable in potency to bovine (b)PTH (1-34) in stimulating 1 alpha-hydroxylase. Direct in vitro incubation of PTH-LP (1-36) with renal slices resulted in stimulation of 1 alpha-hydroxylase activity up to 200% of control levels, comparable to that seen with equimolar concentrations of bPTH-(1-34).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305878 TI - Energy expenditure in humans: effects of dietary fat and carbohydrate. AB - A high-dietary fat intake may be an important environmental factor leading to obesity in some people. The mechanism could be either a decrease in energy expenditure and/or an increase in caloric intake. To determine the relative importance of these mechanisms we measured 24-h energy expenditure in a whole body calorimeter in 14 nondiabetic subjects and in six subjects with non-insulin dependent diabetes mellitus, eating isocaloric, weight-maintenance, high-fat, and high-carbohydrate diets. All subjects were Pima Indians. In nondiabetics, the mean total 24-h energy expenditure was similar (2,436 +/- 103 vs. 2,359 +/- 82 kcal/day) on high-fat and high-carbohydrate diets, respectively. The means for sleeping and resting metabolic rates, thermic effect of food, and spontaneous physical activity were unchanged. Similar results were obtained in the diabetic subjects. In summary, using a whole body calorimeter, we found no evidence of a decrease in 24-h energy expenditure on a high-fat diet compared with a high carbohydrate diet. PMID- 2305879 TI - Paradoxically slow preadipocyte replication and differentiation in corpulent rats. AB - We have investigated the in vitro rate of replication and differentiation of preadipocytes derived from lean (+/+) and obese (cp/cp) male JCR:LA-corpulent (cp) rats in an attempt to identify mechanisms that regulate adipose tissue growth. Cp/cp rats were twofold heavier than age-matched lean rats by 9-10 mo. Cp/cp-derived preadipocytes demonstrated an inherently slower rate of replication than +/+ preadipocytes (population doubling time: cp/cp 52.3 +/- 9.6 h vs. +/+ 19.7 +/- 1.6 h), although the preadipocyte pool in the cp/cp was significantly greater. Cp/cp preadipocytes were resistant to hormonally induced differentiation (19.9 +/- 9.4% of cells accumulated lipid) but differentiated when cocultured with mature adipocytes to the same extent as preadipocytes derived from Sprague Dawley (SD) rats (cp/cp 48.4 +/- 15.2% vs. SD 52.2 +/- 11.9%). In contrast, SD preadipocytes did not differentiate in response to mature adipocytes from +/+ rats (13.8 +/- 5.2%). Our observations suggest that preadipocyte replication and maturation may not be controlled in a coordinated manner. PMID- 2305880 TI - Elevated 1,25-dihydroxyvitamin D3 and intestinal calbindin-D9k in the toothless rat. AB - The toothless (tl) rat is a nonlethal osteopetrotic mutation characterized by systemic skeletal sclerosis, growth plate morphology suggestive of rickets, and morphological evidence of reduced osteoclastic bone resorption. Vitamin D metabolites, serum calcium and phosphorus levels, and the developmental appearance of vitamin D-dependent intestinal calcium binding protein (calbindin D9k) was studied in normal and mutant rats of tl stock from 7 to 35 days of age. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] was found to be significantly elevated in mutant animals by 7 days of age (71 +/- 9 pM, tl/tl vs. 24 +/- 8 pM, +/?) and continued to increase to a peak of 428 pM at the time of weaning. This was 240% higher than normals at this period. The elevated levels of 1,25-(OH)2D3 stimulated a significant and precocious appearance of intestinal calbindin-D9k in mutants, beginning by 14 days of age and reaching their peak levels at 21 days postpartum (25.6 +/- 1.7 micrograms/mg protein, tl/tl vs. 16.4 +/- 1.5 micrograms/mg protein, +/?). The cause of the elevated circulating levels of 1,25 (OH)2D3 in tl rats is unknown but may be due to the low serum phosphorus levels present in these animals. PMID- 2305881 TI - Exercise increases susceptibility of muscle glucose transport to activation by various stimuli. AB - The insulin sensitivity of glucose transport in skeletal muscle is enhanced after exercise. In this study, stimulation of transport of the nonmetabolizable glucose analogue 3-O-methylglucose by the insulin-mimetic agents vanadate and H2O2 was markedly enhanced in rat epitrochlearis muscles 18 h after a bout of swimming. This increase in susceptibility of the glucose transport process in muscle to stimulation by insulin-mimetic agents that act beyond the insulin-binding step provides evidence that the increased insulin sensitivity results from an effect of exercise on a later step in the activation of glucose transport. Hypoxia and insulin appear to stimulate glucose transport by different pathways in muscle as evidenced by an additivity of their maximal effects. The effect of a submaximal hypoxic stimulus on muscle sugar transport was greatly amplified 3 h after exercise. This increase in susceptibility of glucose transport to stimulation by hypoxia after exercise suggests that the increased sensitivity is not limited to the insulin sensitive pathway. In contrast to exercise (i.e., swimming), in vitro muscle contractions did not result in an increase in sensitivity of muscle glucose transport to insulin, raising the possibility that a humoral factor is necessary for this effect. PMID- 2305882 TI - Plasma protein-mediated transport of steroid and thyroid hormones: further comment. PMID- 2305883 TI - Pharyngeal and upper esophageal sphincter manometry in humans. AB - Manometric studies of pharyngeal-upper esophageal sphincter (UES) coordination during swallowing have proven difficult. Asymmetry of the UES makes pressure measurements with a single, unoriented transducer suspect. Perfused systems lack the necessary response rate for measuring peak pharyngeal contraction pressures. Precise quantification of the coordination of pharyngeal contractions and UES relaxations during swallowing is difficult because of rapid pressure changes. We tested a modified solid-state transducer that measures pressures over 360 degrees. This transducer was placed in the proximal UES with a second, single transducer 5 cm proximal. Data were collected and analyzed with an Apple IIe microcomputer. A computer program was developed to measure nine timing sequences, UES resting pressure, nadir of UES relaxation, and pharyngeal contraction pressures. We studied 21 volunteers with six swallows each for dry, 5, 10, and 20 ml of water. Dry swallows differed significantly (P less than 0.05) from wet (5 ml). All timing sequences became progressively longer with increasing bolus size. Residual pressures were unchanged. Timing sequences were also measured for wet (5 ml) and dry swallows in seven volunteers using a Dent sleeve and single perfused orifice in the UES; no differences were seen. PMID- 2305884 TI - Decreased systemic vascular sensitivity to norepinephrine in portal hypertensive rats: role of hyperglucagonism. AB - This study examined whether hyperglucagonism may promote an altered sensitivity to norepinephrine (NE) and contribute to systemic vasodilation in rats with portal hypertension due to portal vein stenosis. Three groups of male Sprague Dawley rats were studied, portal hypertensive, normal controls, and hyperglucagonemic controls. Systemic vascular reactivity was studied by constructing dose-response curves of systemic vascular resistance (SVR) during infusions of increasing doses of NE and calculating NE ED50, the dose of NE that caused 50% of the maximal increase in SVR. Measurement of SVR was based on simultaneous measurements of arterial pressure and cardiac output (CO). Repeated measurements of CO were performed by indicator dilution curves of indocyanine green by means of a fiber-optic catheter placed in the carotid artery. Portal hypertensive rats had a decreased systemic sensitivity to NE, shown by a significant increase in NE ED50 compared with normal controls (60 +/- 8 micrograms vs. 25 +/- 3 micrograms; P less than 0.001). Glucagon levels were markedly increased in the portal hypertensive group (332 +/- 51 pg/ml vs. 176 +/- 22 pg/ml in controls; P less than 0.005). Glucagon infusion in normal rats achieved levels similar to those observed in portal hypertension (305 +/- 48 pg/ml; NS). Systemic vascular sensitivity to NE was also impaired in these hyperglucagonemic normal animals, as shown by an abnormal NE ED50 (69 +/- 16 micrograms; P less than 0.001 vs. controls) that was almost identical to that observed in portal hypertension. These results are consistent with the hypothesis that a reduced sensitivity to NE can contribute to systemic vasodilation in portal hypertension and suggest that hyperglucagonism can play a key role in its pathogenesis. PMID- 2305885 TI - Isobaric intestinal distension in humans: sensorial relay and reflex gastric relaxation. AB - To determine the relationship between perception of segmental intestinal distension and the reflex gastric tone response, we performed in eight healthy volunteers graded isobaric distensions (2.5 min duration at 10 min intervals) of the duodenum and the jejunum using an electronic barostat. We measured gastric tone as intragastric air volume by a separate barostat and the perception score by a graded questionnaire. At the threshold distending pressure for discomfort in the duodenum (23 +/- 2 mmHg), both perception (5.7 +/- 0.2 score; P less than 0.01) and reflex gastric relaxation (148 +/- 35 ml delta gastric vol; P less than 0.01) were elicited. Lower pressures (12 mmHg below the discomfort threshold) failed to produce perception (0.6 +/- 0.4 score), but significant relaxation was still induced (63 +/- 22 ml delta gastric vol; P less than 0.05). In contrast, no significant gastric relaxation occurred at any pressure level tested in the jejunum (up to 27 +/- 2 mmHg), whereas the perception scores paralleled those produced by duodenal distension. This dissociation between symptoms and visceral reflexes suggests that both responses are independently induced by specific mechanisms. PMID- 2305886 TI - Modulation of feline esophageal contractions by bolus volume and outflow obstruction. AB - We studied the effect of bolus volume and esophageal obstruction on esophageal peristalsis by using synchronized video-fluoroscopic and manometric techniques in cats. A specially designed pressure cuff was surgically implanted around the distal esophagus to control the degrees of outflow obstruction. Secondary esophageal peristalsis was evoked by injecting bolus volumes of 3, 6, and 9 ml at cuff pressures of 0, 20, 40, and 60 mmHg. Increases in outflow obstruction reduced the velocity of peristalsis. The amplitude of esophageal contraction increased with increasing outflow obstruction at low bolus volumes but decreased with larger bolus volumes and larger outflow obstruction. In the absence of outflow obstruction, each esophageal contraction traversed the entire esophagus distal to its site of origin, but in the presence of outflow obstruction contractions only traversed part of the esophagus. The incidence and site of failure of propagation was directly related to cuff pressure and bolus volume. The relationship between the onset of manometric pressure complex at a given site in the esophagus to the passage of the bolus from that esophageal site was markedly affected by outflow obstruction. We conclude that esophageal peristalsis can be modulated by the bolus volume and outflow obstruction. PMID- 2305887 TI - Human intestinal water absorption: direct vs. indirect measurements. AB - Distilled water, a carbohydrate-electrolyte (CE; 4% sucrose, 2% glucose, 17.2 meq/l NaCl, and 2.8 meq/l KCl) solution, or a 10% glucose solution, all containing the nonabsorbed indicator polyethylene glycol (PEG) and deuterium oxide (D2O, 30 ppm), were infused (15 ml/min) into the duodenojejunum of seven men by using the triple lumen technique. Net water absorption was determined directly from the change in PEG concentration and was calculated from plasma D2O derived from D2O in the perfusion solutions. The protocol included a 45-min equilibration period followed by a 90-min test period. Intestinal samples were drawn at 10-min intervals from 15 to 45 min and at 15-min intervals thereafter. Blood was drawn at 45, 50, 55, 60, 75, 90, 105, 120, and 135 min. Intestinal samples were analyzed for D2O, Na+, K+, osmolality, PEG, and glucose; blood was analyzed for D2O. Results (+/- SE; positive values secretion, negative values absorption) showed net fluid absorption from distilled water (-9.40 +/- 1.28 ml.h 1.cm-1) and the CE (-13.30 +/- 1.22 ml.h-1.cm-1) solution, but net secretion (4.40 +/- 1.25 ml.h-1.cm-1) from the 10% glucose solution. All values were significantly (P less than 0.05) different from each other. Perfusing the CE solution caused net Na+ and K+ absorption, whereas perfusing the 10% dextrose solution caused net electrolyte secretion. Rates of D2O accumulation in the plasma were independent of the solutions perfused.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305888 TI - Effects of tetrodotoxin on chloride secretion in rabbit distal colon: tissue and cellular studies. AB - The effects of tetrodotoxin (TTX) were examined in muscle-stripped segments of rabbit distal colon and in cells of isolated colonic crypts. Electrical field stimulation (EFS) of the submucosa/mucosa evoked an increase in short-circuit current (ISC) that was due to an increase in chloride secretion. The EFS-evoked response was reduced 81% by 10(-7) M TTX and 30% by 5 X 10(-6) M atropine. Vasoactive intestinal peptide (VIP), carbachol, aminophylline, and 1,1-dimethyl-4 phenylpiperazinium increased ISC. Bumetanide reduced the responses to neural stimulation, aminophylline, and VIP. To determine whether TTX had direct effects on crypt epithelial cells, crypts were isolated and cells were impaled with microelectrodes. Mean resting potential (Vbl) was -67 +/- 1.1 mV (n = 63). VIP and aminophylline depolarized Vbl by 34 +/- 4.6 (n = 13) and 34 +/- 3.5 mV (n = 18), respectively. TTX had no significant effect on resting Vbl or on the responses to VIP or aminophylline. We conclude that stimulation of submucosal neurons in the rabbit distal colon evokes a TTX- and bumetanide-sensitive increase in net chloride secretion that is dependent on the release of acetylcholine and other secretory neurotransmitters. Electrophysiological studies rule out a direct effect of TTX on colonic crypt cells. PMID- 2305889 TI - Effects of PGF2 alpha and of indomethacin on rabbit small and large intestinal motility in vivo. AB - Prostaglandin F2 alpha (PGF2 alpha) has been shown to increase contractility in the small intestine and colon in vitro, and increased mucosal prostaglandin synthesis has been reported in ulcerative colitis. The purpose of this study was to determine the effects of PGF2 alpha and of indomethacin on myoelectric and contractile activity in the rabbit ileum and colon in vivo. PGF2 alpha caused an increase in spike potential frequency and contractile activity in the terminal ileum and proximal and distal colon. Indomethacin alone increased spike potential frequency and contractile activity in the terminal ileum and proximal colon but decreased myoelectric activity in the distal colon. It is concluded that PGF2 alpha may play an important role in modulating intestinal motility, especially in the distal colon but to a lesser extent in the terminal ileum and proximal colon. PMID- 2305890 TI - Villous motility and unstirred water layers in canine intestine. AB - The possibility that villous motility reduces the mucosal unstirred water layer by mechanical stirring was examined. The frequency of contraction of villi was measured by using videomicroscopic techniques while a segment of anesthetized canine jejunum or ileum with its nerve and blood supply intact was maintained in a sealed chamber through which Tyrode solution was perfused. Radioisotopically labeled inulin, H2O, and butyric and lauric acid were used to measure net and/or unidirectional fluxes from the chamber. The unidirectional absorptive transport of H2O and butyric acid but not lauric acid by jejunal segments was significantly correlated with flow through the chamber. Plasma volume expansion increased villous motility but decreased the absorption of H2O and lauric acid. Absorption of butyric acid from the ileum was little different than from the jejunum although the degree of villous motility was less and net water absorption was greater from the ileum. Absorption of butyric acid into dead tissue indicated that passive diffusion into the tissue accounted for between 7 and 25%, depending on flow rate, of the absorption in intact tissue and that nonspecific binding was low. It was concluded that villous motility did not stir the unstirred water layers and was not directly associated with altered transport. PMID- 2305891 TI - Effects of morphine on colonic myoelectric and motor activity in subhuman primates. AB - We investigated the effects of numerous doses of morphine on colonic myoelectric and motor activity in monkeys. In each of four monkeys (Macaca arctoides), combined strain gauge transducers and bipolar electrodes were chronically implanted at four defined sites in the colon and recordings were made for 3 h in fasted, unanesthetized animals before and after intravenous administration of morphine sulfate (10-1,000 micrograms/kg). The basal fasting pattern of colonic motility was characterized by random contractions, nonmigrating clusters of contractions, and migrating individual contractions. Morphine at very low doses (10-25 micrograms/kg) had no effect on colonic motility at any site. At doses of 50-200 micrograms/kg, clusters and migrating contractions were eliminated, but there was an overall increase in the frequency of random contractions without an alteration in contraction amplitude or duration. At morphine doses of 500 and 1,000 micrograms/kg, contraction clusters and migrating contractions also were not seen, but there was a decrease in the colonic motility index caused entirely by a decreased frequency of random contractions. Both stimulation and inhibition were most marked in the sigmoid colon. Morphine has a dose-dependent biphasic effect on colonic myoelectric and contractile activity and alters colonic motility patterns by inhibiting migrating contractions and clusters of contractions. PMID- 2305892 TI - Characterization of the major form of cholecystokinin in human intestine: CCK-58. AB - Acid extracts of human intestines obtained from surgical samples or from organ donors contain cholecystokinin (CCK) immunoreactivity. From surgical samples, extracted and eluted quickly, greater than 75% of the CCK immunoreactivity eluted in the same region as purified canine CCK-58 during analytical reverse-phase high pressure liquid chromatography (HPLC). A major portion of the CCK immunoreactivity from donor intestinal extracts also eluted in this region. This immunoreactivity has been purified from human intestinal extracts by a series of several reverse-phase and cation-exchange chromatographies. Amino acid and microsequence analysis showed that this immunoreactivity is human CCK-58. Tryptic digestion of purified human CCK-58 produced another immunoreactive form that eluted in the position of CCK-8 during analytical reverse-phase HPLC. The immunoreactivity of the trypsin-digested material was 2.6-fold higher than that of an identical sample of CCK-58 incubated without trypsin. Thus the carboxyl terminal antibody used for radioimmunoassay cross-reacts greater than twofold less with human CCK-58. This diminished cross-reactivity would lead to an underestimation of the relative proportions of CCK-58 in tissue and plasma extracts. If CCK-58 is the major circulating form this diminished cross reactivity would also lead to underestimations of the circulating levels of total CCK. Determination of human CCK-58 structure confirms that one of the major components of human CCK that expresses biological activity is CCK-58. PMID- 2305893 TI - Contribution of Cl(-)-OH- exchange to electroneutral NaCl absorption in rat distal colon. AB - Neutral NaCl absorption is the predominant Na+ absorptive process in rat distal colon. Whether this neutral NaCl absorptive process represents Na(+)-Cl- cotransport or dual ion exchanges of Na(+)-H+ and Cl(-)-OH- has been uncertain. Recent studies using rat colonic brush-border membrane vesicles (BBMVs) have described a Na(+)-H+ exchange mechanism and have proposed that net NaCl absorption occurs via a dual ion exchange process. To date, however, an anion exchanger on the colonic apical membrane has not been identified. To determine whether a Cl(-)-OH- exchange process is present, 36Cl uptake was evaluated across rat distal colonic BBMVs. A pH gradient (7.7 in/5.5 out) stimulated active Cl- uptake. Cl- uptake was not significantly affected by the presence of a valinomycin-induced K+ diffusion potential (inside positive), suggesting that a Cl- conductive pathway is not present in these membranes. The pH gradient stimulated Cl- uptake was a saturable function of the Cl- concentration with a Km of 14.3 +/- 5.0 mM and a Vmax of 20.4 +/- 5.5 nmol.mg protein-1.30 s-1 and was almost completely inhibited by 1 mM concentrations of SITS and DIDS, inhibitors of anion exchange processes in other epithelia. Inward gradients of Na+, K+, or Na+ and K+ did not further stimulate initial Cl- uptake, suggesting that coupling of Na+ and Cl- movement does not occur by a cotransport mechanism. Thus a Cl(-) OH- exchange process is present in rat distal colonic BBMVs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305894 TI - Beneficial effects of two forms of NO administration in feline splanchnic artery occlusion shock. AB - We studied the effects of nitric oxide (NO) solution and acidified sodium nitrite (NaNO2), which produces NO, in splanchnic artery occlusion (SAO) shock in cats. NO is thought to be endothelium-derived relaxing factor (EDRF), a labile substance having several potentially valuable biological effects. Anesthetized cats subjected to total occlusion of the celiac, superior mesenteric, and inferior mesenteric arteries for 120 min, followed by reperfusion, usually died approximately 60 min after reperfusion. NO infusion significantly improved survival time in SAO-shock cats compared with those receiving vehicle (P less than 0.005). Administration of NO also attenuated the increase in plasma activities of the lysosomal hydrolase cathepsin D (P less than 0.05), total amino nitrogen (P less than 0.001), and of the cardiotoxic peptide, myocardial depressant factor (MDF) (P less than 0.001). SAO-shock cats treated with NaNO2 at pH 2.0 also exhibited lower plasma cathepsin D (P less than 0.001), amino nitrogen (P less than 0.05), and MDF activities (P less than 0.01), and survival time was also significantly improved (P less than 0.02). The same dose of NaNO2 infused at pH 7.4 failed to exert any significant protective effect. These results indicate that NO exerts beneficial effects in SAO shock in cats and suggest that exogenously administered NO may be a potentially useful therapeutic agent in splanchnic ischemic shock, probably via a cytoprotective rather than a vasodilator effect. PMID- 2305895 TI - Effects of osmotic stresses on isolated rat hepatocytes. I. Ionic mechanisms of cell volume regulation. AB - Isolated hepatocyte suspensions were exposed to hypotonic and hypertonic stresses and serial cell volume measurements were made with an electronic particle size analyzer. With the exposure to hypotonic (160 mosM) buffer, hepatocytes swelled within 30-60 s as osomometers [relative volume (RV) = 1.44 +/- 0.08] and subsequently underwent regulatory volume decrease (RVD) back toward the resting (isotonic) level (1.16 +/- 0.05). This volume recovery was blocked by 65 mM extracellular K+ concentration and inhibited by barium (1 mM) and quinine (0.5 mM) but not by bumetanide (0.1 mM). Chloride depletion inhibited RVD by approximately 40% while 0.5 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) blocked the recovery by almost 90%. Calcium deprivation had no effect on RVD, nor did ouabain, amiloride, or sodium replacement. When exposed to buffer made hypertonic by addition of 200 mM sucrose, cells shrunk as osmometers (RV = 0.74 +/- 0.02) but did not exhibit regulatory volume increase (RVI). However, when cells that had first undergone RVD were reexposed to isotonic medium (relative hypertonic stress) RVI could be demonstrated from RV 0.77 +/- 0.17 to 0.91 +/- 0.20. This response was dependent on sodium, partially dependent on bicarbonate and chloride, and inhibited by the Na(+)-H+ exchange inhibitor amiloride (1 mM) but not by DIDS. Our findings suggest that RVD in rat hepatocytes is mediated by quinine- and barium-sensitive K+ conductance and DIDS sensitive anion conductance, which is partly accounted for by Cl-; RVI is mediated by activation of Na(+)-H+ exchange coupled with a bicarbonate- and chloride-dependent but DIDS-insensitive process. PMID- 2305896 TI - Effects of osmotic stresses on isolated rat hepatocytes. II. Modulation of intracellular pH. AB - To assess the roles of acid-base transport systems in cell volume regulation in rat hepatocytes, intracellular pH (pHi) was measured in subconfluent monolayers loaded with 2'-7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) after exposure to hypotonic and relative hypertonic media, interventions that stimulate regulatory volume decrease (RVD) and increase (RVI), respectively. During RVD, pHi decreased from 6.98 +/- 0.11 to 6.85 +/- 0.08 in the absence of HCO3- and from 7.26 +/- 0.10 to 7.19 +/- 0.06 in its presence. Omission of Na+ or addition of 1 mM amiloride prevented the decline in pHi. Acute withdrawal or replacement of Na+ in hypotonic medium resulted in a slower rate of fall or recovery in pHi, respectively, than when the same maneuvers were carried out in isotonic medium. In contrast, during RVI, pHi increased from 6.86 +/- 0.11 to 7.15 +/- 0.15 in the absence of HCO3-, a rise in pHi that was also completely abolished by Na+ removal or by 1 mM amiloride. In the presence of HCO3-, the rise in pHi was less marked than in its absence, although net acid efflux was greater because of a greater intracellular buffering capacity. Cl- removal in the presence of HCO3- had no effect on the change in pHi during either RVD or RVI. Perfusion with 0.5 mM 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) during RVD lowered pHi further and accentuated the subsequent pHi rise seen after the return to isotonic medium. These data suggest that Na(+)-H+ exchange in rat hepatocytes is downregulated during RVD and activated during RVI. Cl(-)-HCO3- exchange does not appear to be involved in hepatocyte volume regulation. PMID- 2305897 TI - Vagal interactions on brain stem neurons receiving input from the proximal stomach in cats. AB - Gastric vagal fibers on the proximal stomach that join the dorsal and ventral vagal trunks were electrically stimulated to localize and evaluate brain stem neuronal interactions in anesthetized cats. The brain stem responses were located in nucleus tractus solitarius in the dorsomedial, caudal region of the medulla oblongata. There was no significant difference in the mean latency of the gastric vagally evoked brain stem response between the dorsal and ventral vagal trunks. The responses consisted of single or multiple spikes with a mean latency of approximately 290 +/- 50 (SD) ms. Forty-one percent, or 168 unitary responses of the 406 total responses recorded, showed convergence of proximal gastric vagal input from both the dorsal and ventral vagal trunks on the same recording site or on the same cell. Of those unitary responses that received convergent proximal gastric vagal input, 95 unitary responses (57%) showed convergence of input to the same area, on different cells at the same recording site during a single trial. Seventy-three single units (43%) received convergent input from proximal gastric vagal afferent fibers in both the dorsal and ventral trunks. Fifty-two, or 71%, of the single unit convergent responses were excitatory in nature, whereas the remaining 29% were inhibitory. These data demonstrated that proximal gastric vagal afferent fibers that join the dorsal and ventral trunks converged on a significant number of single neurons in the brain stem. The convergent response was synaptically secure and exerted an identifiable biasing effect on the response of the brain stem neuron.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305898 TI - Respiratory activity in retrotrapezoid nucleus in cat. AB - An anatomic projection from the retrotrapezoid nucleus to the ventral respiratory group in cat was previously reported by our laboratory (J. C. Smith, D. E. Morrison, H. H. Ellenberger, M. R. Otto, and J. L. Feldman. J. Comp. Neurol. 281: 69-96, 1989). We now report on the properties of neurons in the retrotrapezoid nucleus, investigated with extracellular recording techniques in 10 chloralose urethane anesthetized, paralyzed, mechanically ventilated cats. A ventral exposure of the medulla facilitated recording from neurons in the retrotrapezoid nucleus, located ventral to the facial nucleus near the medullary surface. Respiratory-modulated, as well as irregularly discharging, spontaneous unit activity was recorded within the retrotrapezoid nucleus. Twelve respiratory modulated units in the retrotrapezoid nucleus exhibited inspiratory (8 units), expiratory (3 units), or multimodal (1 unit) discharge patterns. Chemical activation of an inspiratory unit in the retrotrapezoid nucleus by pressure ejection of DL-homocysteic acid (less than 0.5 nl of 10 mM solution) demonstrated that the respiratory-modulated activity originated from the cell soma and not fibers of passage coursing through the retrotrapezoid nucleus region. Electrical microstimulation (20-40 microA, approximately 70-microseconds duration, biphasic pulse) within the ipsilateral ventral respiratory group elicited antidromic activation of 7 units in the retrotrapezoid nucleus, three of which were not spontaneously active. Electrical stimulation (5-80 microA, 70-microseconds pulse width, 100 Hz, 400- to 500-ms trains) at sites within retrotrapezoid nucleus affected the respiratory motor output when delivered during late expiration, eliciting premature onset of inspiration. These results suggest that retrotrapezoid nucleus projections to the ventral respiratory group (and dorsal respiratory group) may influence respiratory timing and pattern, perhaps by conveying signals originating in the rostral ventrolateral medulla that result from ventral surface perturbations. PMID- 2305899 TI - Adenosine A1 receptor-mediated inhibition of surfactant secretion in rat type II pneumocytes. AB - Phosphatidylcholine secretion in type II pneumocytes has been reported to be stimulated by P1 and P2 purinoceptor agonists. P1 receptors are divided into A1 and A2 subtypes with opposite effects on the levels of adenosine 3',5'-cyclic monophosphate (cAMP). Stimulated secretion in type II cells is mediated by the A2 receptor and accompanied by an increase in cAMP concentration. We now report evidence suggesting the existence of an A1 receptor-inhibiting secretion in type II cells from adult rats. The rate of phosphatidylcholine secretion was approximately doubled by 5'(N-ethylcarboxyamido) adenosine (NECA), terbutaline, and forskolin, all of which increase cAMP levels. Adenosine deaminase increased the stimulatory effect of these agonists to approximately three-fold but it had not effect on secretion stimulated by agonists which do not increase cAMP levels. The effect of adenosine deaminase on terbutaline-stimulated secretion was antagonized by selective adenosine A1 receptor agonists, N6-cyclopentyladenosine (CPA) and 1-deaza-2-chloro-N6-cyclopentyladenosine (DCCA). The maximum inhibitory effects of CPA and DCCA were achieved at 10(-9) M and 10(-11) M, respectively. At these concentrations CPA and DCCA had no effect on the rate of basal secretion or on terbutaline-stimulated secretion in the absence of adenosine deaminase. We suggest that adenosine deaminase stimulates phosphatidylcholine secretion by removing adenosine that occupies A1 receptors, thus reversing inhibition of cAMP mediated secretion. PMID- 2305900 TI - Epithelial effects on tracheal smooth muscle tone: influence of muscarinic antagonists. AB - The tracheobronchial epithelium produces factor(s) that modulate the constrictor and relaxant response of airway smooth muscle. The present study sought to determine whether the tracheobronchial epithelial inhibitory effect on trachealis smooth muscle tension is under muscarinic receptor control. Studies were performed on 195 strips from 13 rabbits. In strips in which the epithelium was intact, pirenzepine (an M1 receptor antagonist) produced a dose-related (10(-8) and 10(-7)M) rightward shift (P less than 0.01 for each) and gallamine (an M2 antagonist) produced a progressive (10(-8) and 10(-7)M) leftward shift of the acetylcholine concentration responses (P less than 0.01 for each). In strips in which the epithelium was removed mechanically, neither pirenzepine nor gallamine had any effect on the acetylcholine responses. In acetylcholine precontracted (5 x 10(-6) M) muscle strips with epithelium intact, addition of pirenzepine (10( 7)M) produced a significant (P less than 0.01) reduction in steady-state tension, whereas administration of gallamine tended to increase tension, (P = NS). Neither pirenzepine nor gallamine had any effect on steady-state tension in strips in which the epithelium was removed. These results indicate that the magnitude of the tracheobronchial epithelial inhibitory effect on smooth muscle tension is under muscarinic control. Specifically, M1 receptor blockade augments and M2 receptor blockade inhibits the magnitude of the tracheobronchial epithelial effect. PMID- 2305901 TI - Calcitonin gene-related peptide in human nasal mucosa. AB - To explore the potential range of functions for calcitonin gene-related peptide (CGRP) in human mucosa, we quantified human inferior turbinate nasal mucosal CGRP content by radioimmunoassay, localized CGRP-immunoreactivity by immunohistochemistry, detected 125I-CGRP binding sites by autoradiography, and tested the ability of CGRP to induce submucosal gland secretion in short-term explant culture of human nasal mucosa. Nasal mucosa contained 0.45-0.54 pmol CGRP/g wet wt (n = 18). Immunoreactive CGRP was found in nerve fibers that densely innervated the walls of small muscular arteries arterioles. Venules and venous sinusoids were innervated by individual CGRP staining fibers. Occasional CGRP-containing nerve fibers were also noted adjacent to submucosal gland acini, near the epithelial basement membrane, and between epithelial cells. Specific 125I-CGRP binding sites were concentrated on small muscular arteries and arterioles. CGRP (4 microM) did not stimulate glycoconjugate or lactoferrin release from mucosal explants. These results indicate that in the human nasal mucosa, CGRP is present in nerve fibers, which most likely represent nociceptive sensorimotor nerves that innervate vascular structures (muscular arteries, arterioles, veins and venous sinusoids). It is likely that CGRP release from sensory neurons may play a role in the regulation of vasomotor responses, but no evidence for a role of CGRP in glandular secretion was found. PMID- 2305902 TI - Congenital syphilis: reporting and reality. PMID- 2305904 TI - An evaluation of external cause-of-injury codes using hospital records from the Indian Health Service, 1985. AB - To evaluate the usefulness of International Classification of Diseases external cause-of-injury and poisoning codes (E codes) for public health surveillance of nonfatal injuries, we analyzed E codes from Indian Health Service (IHS) hospital records. E codes for unknown or unspecified causes were used for 25 percent of records. At two hospitals, 63 percent of E codes assigned by independent coders agreed; another 18 percent matched on general cause-of-injury groups. With uniform guidelines and increased training, E coding could provide a valuable, cost-effective method of quantifying and characterizing severe, nonfatal injuries. PMID- 2305903 TI - The impact of legalized abortion on adolescent childbearing in New York City. AB - In this paper we estimate the impact on adolescent childbearing of the liberalization of the New York State abortion law in 1970. Using Box-Jenkins time series techniques to analyze monthly data on the number of births to White and Black adolescents from January 1963 to December 1987, we found that the level of births to Black adolescents living in New York City fell 18.7 percent, approximately 142 fewer births per month, after the law became effective; the level of White births fell 14.1 percent, approximately 111 fewer births per month. Projections based on the fitted model suggest that a ban on legalized abortion today would have a major impact on adolescent childbearing in New York City as well as other parts of the country, although the magnitude of the change would vary according to local conditions. PMID- 2305905 TI - Cardiovascular deaths among Alaskan Natives, 1980-86. AB - Average annual, age-adjusted death rates from cardiovascular diseases and atherosclerosis from 1980-86 among Alaskan Natives were lower than rates among other Alaskans (162.0 vs 242.1; RR = 0.67), while death rates from other causes were higher (954.4 vs 618.6; RR = 1.54). These suggest that Alaskan Natives have less cardiovascular disease than other populations. Additional research on the role of marine omega-3 fatty acids is needed. PMID- 2305906 TI - Salmonella arizona infections in Latinos associated with rattlesnake folk medicine. AB - In 1987 two Los Angeles County (California) hospitals reported four Latino patients with serious Salmonella arizona (Salmonella subgroup 3) infections who gave a medical history of taking rattlesnake capsules prior to illness. Capsules supplied by the patients or household members grew Salmonella arizona. We reviewed surveillance data for this Salmonella species and conducted a case control study to determine the magnitude of this public health problem. Eighteen (82 percent) of the 22 Latino cases in 1986 and 1987 who were questioned reported ingesting snake capsules compared to two (8 percent) of 24 matched Latino controls with non-subgroup 3 salmonellosis or shigellosis (matched pair odds ratio = 18.0, CI = 4.2, 76.3). An average of 18 cases per year of Salmonella arizona were reported in the county between 1980 and 1987. In this investigation the majority of S. arizona cases reporting snake capsule ingestion had underlying illnesses such as acquired immunodeficiency syndrome (AIDS), diabetes, arthritis, cancer. The capsules were obtained primarily from Tijuana, Mexico and from Los Angeles, California pharmacies in Latino neighborhoods. Despite publicity and attempts to remove the capsules from sale in California, Salmonella arizona cases associated with snake-capsule ingestion continue to occur. PMID- 2305907 TI - Use of medical care for chest pain: differences between blacks and whites. AB - Data from a 1980, community-based survey of adult residents of Edgecombe County, North Carolina were analyzed to examine differences between Blacks and Whites in the reported use of medical care after experiencing chest pain. Of all adults (N = 302) with chest pain in the year prior to interview, 49 percent of Blacks and 27 percent of Whites did not see a physician following the chest pain (difference = 22%, 95% CI = 12, 33). A multivariable analysis found that although the association between race and utilization was reduced at poverty levels of income, it was not explained by differences in demographic characteristics, health status or other dimensions of access to care. PMID- 2305908 TI - Beliefs about AIDS, use of alcohol and drugs, and unprotected sex among Massachusetts adolescents. AB - In August 1988, 1,773 Massachusetts 16-19-year-olds were surveyed by telephone using anonymous random digit dialing; response rate 82 percent. Logistic regression tested whether alcohol and drug use, perceived susceptibility to human immunodeficiency virus (HIV), severity of HIV if infected, effectiveness of condoms in preventing infection, barriers to condom use, and behavioral cues such as exposure to media or personal communication about acquired immunodeficiency syndrome (AIDS) were independently related to condom use. Among sexually active respondents, (61 percent of those interviewed) 31 percent reported always using condoms. Respondents who believed condoms are effective in preventing HIV transmission and worried they can get AIDS were 3.1 and 1.8 times, respectively, more likely to use condoms all the time. Respondents who carried condoms and who had discussed AIDS with a physician were 2.7 and 1.7 times, respectively, more likely to use them. Those who believed condoms do not reduce sexual pleasure and would not be embarrassed if asked to use them were 3.1 and 2.4 times, respectively, more likely to use condoms. Teens who averaged five or more drinks daily or used marijuana in the previous month were 2.8 and 1.9 times, respectively, less likely to use condoms. Among respondents who drink and use drugs, 16 percent used condoms less often after drinking and 25 percent after drug use. Those counseling adolescents about HIV should assess and discuss beliefs outlined in the Health Belief Model, as well as their alcohol and drug use. PMID- 2305909 TI - The growing proportion of female physicians: implications for US physician supply. AB - This study analyzes how the growing proportion of women in the United States physician population will affect the amount and type of physician services available to the US population. Female physicians work fewer hours per week, are slightly less likely to be in patient care, and tend to enter different specialties than male physicians. Female physicians also have higher retirement rates than male physicians, but due to their lower mortality rates, have work lives nearly as long as male physicians. We examined how the changing composition of the physician population will affect the availability of physician services by comparing historical and projected trends for the number of active post-residency physicians with comparable trends for a full-time-equivalent measure of physician supply. The full-time-equivalent measure takes into account the different labor supply behavior of key subpopulations (e.g., women and graduates of US versus foreign medical schools). The results suggest that the changing composition of the physician population will reduce the growth of effective physician supply between 1986 and 2010 but only by four percentage points. PMID- 2305910 TI - Cryptosporidium infection in Oregon public health clinic patients 1985-88: the value of statewide laboratory surveillance. AB - To evaluate the utility of statewide laboratory Cryptosporidium surveillance, we screened stools from all 5,256 patients evaluated at local health departments for parasitic disease from January 1985 through June 1988. Fifty-seven patients (1.1 percent) were found to have Cryptosporidium. Seasonal peaks in positivity were observed in the spring, summer, and early autumn months. In children, younger age was associated with higher positivity rate of cryptosporidiosis. As a result of these surveillance efforts, Oregon's first known outbreak of cryptosporidiosis was detected and investigated during 1988. Twenty-five persons were infected, including children, parents, and staff associated with two day care centers. The cost of routine screening for Cryptosporidium was $1.13 per specimen in our laboratory, and we consider it useful. PMID- 2305911 TI - A comparison of alcohol sales data with survey data on self-reported alcohol use in 21 states. AB - We used data from 21 states that participated in the 1985 Behavioral Risk Factor Surveillance System to compare state-specific per capita self-reported alcohol consumption and the prevalence of three drinking behaviors with state-specific per capita sales. The correlation coefficient for per capita sales and per capita self-reported consumption for the 21 states was 0.81. Per capita sales were also significantly correlated with the prevalence of self-reported heavier drinking, binge drinking, and drinking and driving; the corresponding correlation coefficients were 0.74, 0.59, and 0.51. These findings suggest that states with higher per capita sales of alcohol also have higher rates of self-reported consumption and drinking patterns suggestive of high-risk behavior. PMID- 2305912 TI - Cesarean section use and source of payment: an analysis of California hospital discharge abstracts. AB - This study assessed the relation between payment source and cesarean section use by analyzing California data on hospital deliveries. Of 461,066 deliveries in 1986, cesarean sections were performed in 24.4 percent. Women with private insurance had the highest cesarean section rates (29.1 percent). Successively lower rates were observed for women covered by non-Kaiser health maintenance organizations (26.8 percent), Medi-Cal (22.9 percent), Kaiser (19.7 percent), self-pay (19.3 percent), and Indigent Services (15.6 percent). Vaginal birth after cesarean (VBAC) occurred more than twice as frequently in women covered by Kaiser (19.9 percent) and Indigent Services (24.8 percent), compared to those with private insurance (8.1 percent). Sizable, although less pronounced, associations between payment source and cesarean section use were noted for the indications of breech presentation, dystocia, and fetal distress. Accounting for maternal age and race/ethnicity did not alter these findings. Variations in the use of cesarean section have a substantial financial impact on health care payors. PMID- 2305913 TI - The effects of case definition in maternal screening and reporting criteria on rates of congenital syphilis. AB - Reports of congenital syphilis in 1987 were reviewed to determine how new national guidelines for defining congenital syphilis would influence reported rates in Los Angeles County. After reviewing all reported reactive serologic tests for syphilis, we found 166 additional cases, resulting in a 426 percent increase in the 1987 reported rate of congenital syphilis. Rates of congenital syphilis are dependent upon surveillance practices, screening policies, and case definition. PMID- 2305914 TI - End state renal disease among Native Americans, 1983-86. AB - We used data reported to Medicare from 1983 through 1986 to determine the incidence of end-stage renal disease (ESRD) among Native Americans and Whites in the United States. The 1,075 Native American cases represented an annual incidence, age-adjusted to the White population, of 269 per million, 2.8 times the rate for Whites. Fifty-six percent of Native American cases and 27 percent of the White cases were attributed to diabetes, indicating that ESRD is a major problem. Diabetes control provides the greatest opportunity for prevention. PMID- 2305915 TI - Mortality from infectious diseases among New Mexico's American Indians, Hispanic whites, and other whites, 1958-87. AB - To examine ethnic differences in infectious disease-related mortality in New Mexico's American Indian, Hispanic White and other White populations, we analyzed vital records data from 1958 to 1987. We found that for most infectious causes, American Indians had the highest mortality rates, followed by Hispanics. The state's minority populations remain at increased risk for infectious disease mortality. PMID- 2305916 TI - Feasibility of a telephone survey to study a minority community: Hispanics in San Francisco. AB - In two random digit dialing surveys conducted among Hispanics using a modified Mitofsky-Waksberg procedure, we found low refusal rates (4.7% and 3.1%), low assumed noncontact rate (14.0% and 18.3%), and high response rates (88.6% and 88.4%) with limited investment in time (1.58 hours and 1.66 hours per completed interview). These results suggest that Hispanics are willing to participate in telephone surveys and that this method may be feasible and useful for research and evaluation purposes. PMID- 2305917 TI - Sex-specific and race-specific hip fracture rates. AB - Sex-, race- and age-specific hip fracture rates were determined using Health Care Financing Administration data for Medicare-reimbursed hip fracture hospitalizations from 1980 to 1982. Rates were highest in White women, lowest in Black men, and intermediate in White men and Black women. Proportions of hip fracture patients dying during hospitalization and those discharged to nursing homes, respectively, were: White men (10.5%; 49%); Black men (9.3%; 32%); White women (5.0%; 54%); and Black women (8.2%; 30%). PMID- 2305918 TI - The epidemiology of vulvovaginal candidiasis: risk factors. AB - The effects of personal hygiene, sexual history, diet, and stress on the risk of vulvovaginal candidiasis were estimated from a case-control study of students attending a public university during 1986-87. Data from medical records and self administered questionnaires were used to compare 85 cases to 1,245 other students using the Health Service, and to 113 subjects chosen from the total student population. Frequent sexual intercourse was the strongest risk factor (seven or more times a week versus none): OR = 4.3; 95% CI: 1.4, 12.9 (for cases versus Health Service controls). PMID- 2305919 TI - Recurring urinary tract infection: incidence and risk factors. AB - Urinary tract infection (UTI) is a common infection among young women, with a high recurrence rate. This study documents the six-month incidence of second UTI among a cohort of women with one initial UTI and the factors associated with recurrence. Among the cohort of 113 women, 30 (26.6 percent) experienced at least one culture-confirmed recurrence within the six months following initial infection. The presence of hematuria and urgency as symptoms of initial infection were the strongest predictors of second infection. Behavioral factors associated with initial infection (frequency of sexual intercourse, diaphragm use, and voiding after sexual intercourse) did not distinguish between women who would and would not experience a second UTI during the six-month follow-up period. PMID- 2305920 TI - Potential for Lyme disease in Maine: deer survey of distribution of Ixodes dammini, the tick vector. AB - A survey of deer brought to tagging stations at 24 sites in Main revealed the presence of the deer tick, Ixodes dammini, on 5.1 percent of deer. Ticks were found almost exclusively on deer from southwest coastal sites in the state. The potential for endemic Lyme disease in coastal Maine merits further study. PMID- 2305922 TI - TEEN TALK: peer groups addressing teen pregnancy. PMID- 2305921 TI - New FDA drug approval policies and HIV vaccine development. PMID- 2305923 TI - Risk behavior change in gay men. PMID- 2305924 TI - Freestanding birth centers: safe, sensitive care. PMID- 2305925 TI - Longevity and left-handedness. PMID- 2305926 TI - Lead exposure in indoor firing ranges. PMID- 2305927 TI - A crossroad. PMID- 2305928 TI - Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. AB - Schwannoma, a benign tumor of peripheral nerve sheath, infrequently contains melanin and even less frequently features psammoma bodies. Forty schwannomas that displayed both findings were obtained from 31 patients, aged 10 to 63 years. Seventeen patients (55%) had the complex of myxomas, spotty pigmentation, and endocrine overactivity, a familial syndrome. Six (19%) had multiple tumors. Tumor sites included posterior spinal nerve roots (11 tumors), alimentary tract (11 tumors), and bone (three tumors). Two-thirds of the neoplasms caused symptoms. Grossly, the tumors were black, brown, or blue, encapsulated, and solid or spongy. Microscopically, they were circumscribed but incompletely encapsulated; they contained spindle and epithelioid cells, melanin, psammoma bodies, and fat. The spindle cells were arranged in interlacing fascicles, and exhibited whorling and occasional nuclear palisading. Immunostaining revealed that the tumors were positive for S-100 protein and vimentin and negative for glial fibrillary acidic protein, actin, and keratin. Ultrastructurally, the cells features elongated processes, continuous basal lamina, melanosomes, and intercellular long-spacing collagen. Twenty-one patients (68%) were alive without evidence of the neoplasm; two of these each had two local recurrences. Seven patients died, three (10%) as a result of metastasis. Three patients were lost to follow-up. PMID- 2305929 TI - Serous borderline tumors of the peritoneum. AB - The clinicopathological features of 25 cases of peritoneal serous neoplasms histologically identical to noninvasive implants of ovarian serous borderline tumors but with minimal or no ovarian surface involvement were reviewed. The patients ranged in age from 19 to 53 (mean, 31) years; 18 of them were under 35 years of age. Infertility and abdominal pain were the most common presenting complaints. An extraovarian mass was present in two patients; adhesions or granularity of peritoneal surfaces were described in 23 of them. In 21 cases only the pelvic peritoneum was involved; the upper abdominal peritoneum was involved additionally in four cases. Most of the women were treated by hysterectomy, bilateral salpingo-oophorectomy, and omentectomy; six of them received chemotherapy postoperatively and two received both chemotherapy and radiation therapy. Nine women had a more limited operation to preserve their fertility. The 25 patients were followed for 4 to 13.9 (mean, 8) years. There was no clinical evidence of recurrence in 21 women. Borderline tumor recurred in two patients, who remained well for 1.7 and 2 years after excision of the recurrent tumor. Invasive low-grade serous carcinoma of the peritoneum developed in one woman who was living with extensive intra-abdominal tumor at the last follow-up examination. One woman died of disseminated SBT, which was diagnosed cytologically but not confirmed by biopsy. PMID- 2305930 TI - Capsular penetration in prostate cancer. Significance for natural history and treatment. AB - We established the location and extent of complete capsule penetration by prostate cancer in 176 radical prostatectomy specimens and related these findings to cancer volume, location of positive surgical margins, and presence of nodal metastases or seminal vesicle (SV) invasion. Extent of capsule penetration, cancer volume, and positive nodes/SV were strongly intercorrelated. It could not be shown that capsule penetration was related to prognosis independently of its correlation with cancer volume. Twelve cubic centimeters was a critical cancer volume; above that, combinations of extensive capsule penetration, positive surgical margins, and positive nodes/SV were almost universal. In cancers under 12 cc, positive surgical margins were only moderately correlated with cancer volume; they often represented surgical resection into the capsule rather than a complication of capsule penetration by tumor and were most common at the apex, where dissection is most difficult. In non-transition zone cancers (148 cases), capsule penetration was most common posterolaterally, where nerves penetrate the capsule. In transition zone cancers (28 cases), capsule penetration was much less common and was located more anteriorly. Apical positive margins were also relatively common in transition zone cancers, but seminal vesicle invasion was never seen. PMID- 2305931 TI - Chromophobe cell carcinoma: analysis of five cases. AB - Five cases of a recently characterized renal neoplasm, chromophobe cell carcinoma, encountered during an ultrastructural and DNA flow cytometric study of renal cortical neoplasms are described. These tumors usually are dark on gross examination and often are associated with focal hemorrhage or necrosis. Microscopically the tumor cell cytoplasm ranges from clear to eosinophilic, potentially eliciting a broad differential diagnosis encompassing renal cell carcinoma and oncocytoma. Ultrastructural studies disclosed the diagnostically required numerous complex cytoplasmic vesicles of unknown composition and origin, and DNA ploidy studies revealed an aneuploid cell population in three of five cases, which correlates with the malignant potential. PMID- 2305932 TI - A rural surgeon's perspective on general surgery. PMID- 2305933 TI - Colorectal cancer in a small rural hospital. AB - Over a 20-year period, 168 cases of colorectal cancer were treated in a 50-bed rural hospital by 1 surgeon. The majority of the patients were older than 70 years of age. The stage of disease was comparatively advanced, with 71% of the patients having nodal or distant metastases, 19% with bowel obstruction, and 8% with perforation. The operability and resectability rates were 100% and 96%, respectively. The crude 5-year survival was 50% for the entire series. The 5-year survival after curative operations in which there was no gross residual tumor at the end of the operation was 63%, and the 5-year survival for resection of localized node-negative disease was 81%. The wound infection rate was 2%, and the operative mortality rate was 1% for combined elective and emergency operations. The results of treatment of colorectal cancer in small rural hospitals are infrequently reported, and this series may be compared with the published results from large teaching institutions. PMID- 2305934 TI - Angiography in poor-risk patients with massive nonvariceal upper gastrointestinal bleeding. AB - The purpose of this retrospective study was to determine the diagnostic and therapeutic usefulness of gut angiography in patients with massive upper gastrointestinal bleeding from a nonvariceal source. All patients (n = 64) in this category who underwent a gut angiogram between 1980 and 1986 were studied. Pre-angiogram endoscopy was attempted in all patients and was nondiagnostic in 14 (22%). Contrast extravasation at angiography was seen in 25 of 64 patients (39%), and in over half of these patients endoscopy was nondiagnostic (n = 11) or wrong (n = 3). Attempts to control bleeding in this group by selective arterial embolization (n = 14) or intra-arterial vasopressin (n = 11) successfully averted operation in 13 of 25 patients (52%) and was associated with a 50% reduction in mortality (83% versus 38%). Selective embolization of vessels thought to be bleeding on clinical grounds without evidence of contrast extravasation (i.e., "blind" embolization) was not helpful in controlling hemorrhage. Urgent gut angiography in patients with massive upper gastrointestinal bleeding of arteriocapillary source is a useful diagnostic and therapeutic maneuver and warrants continued application in this group of poor-risk patients. PMID- 2305935 TI - Reassessment of primary resection of the perforated segment for severe colonic diverticulitis. AB - Primary resection with colostomy has been widely adopted during the past decade for the treatment of patients with severe complications of diverticulitis. Because of this, a retrospective review was performed of all patients undergoing surgery for colonic diverticular disease during the two time periods 1974 to 1978 (n = 196) and 1982 to 1986 (n = 230). Forty-three patients had abscess or peritonitis from 1974 to 1978, whereas 52 had these complications from 1982 to 1986. Colostomy and drainage alone were used for 31 of 43 patients (72%) from 1974 to 1978, while primary resection with colostomy was used for 39 of 52 patients (75%) from 1982 to 1986 (p less than or equal to 0.5). Despite this shift in treatment method, mortality increased from 14% in 1974 to 1978 to 19% in 1982 to 1986 (p = NS). Patients with peritonitis had identical mortalities (22%) during both intervals. Patients with abscess experienced an increase in mortality from 8% in 1974 to 1978 to 15% in 1982 to 1986 (p = NS). The widespread use of primary resection for patients with severe complications of diverticulitis appears not to have altered mortality for those with diffuse peritonitis and may have worsened the outcome for those with abscess. PMID- 2305936 TI - Effect of catabolic hormone infusion on protein turnover and amino acid uptake in skeletal muscle. AB - Increased plasma levels of the catabolic hormones glucagon, epinephrine, and cortisol have been implicated in mediating various metabolic alterations in trauma and sepsis. Their role in altered protein turnover and amino acid transport in skeletal muscle during sepsis, however, is not known. In the current study, rats were infused with a mixture of the catabolic hormones for 16 hours. Control animals were infused with vehicle solution. Protein synthesis and degradation rates were measured in incubated, intact soleus muscles as incorporation of 14C-phenylalanine into protein and release of tyrosine into incubation medium, respectively. Muscle amino acid uptake was determined by measuring the intracellular to extracellular ratio of [3H]-alpha-aminoisobutyric acid after incubation for 2 hours. Infusion of catabolic hormones for 16 hours resulted in elevated plasma glucose and lactate levels, reduced plasma concentrations of most amino acids, and accelerated muscle protein breakdown, similar to previous findings in septic rats. Protein synthesis rates and amino acid uptake in incubated muscles were not significantly different in control and hormone-infused rats. The current study suggests that increased muscle proteolysis in sepsis and severe injury may be mediated in part by catabolic hormones. In contrast, reduced muscle protein synthesis and amino acid uptake are probably signaled by other substances or mechanisms. PMID- 2305937 TI - The iliac crest and the radial forearm flap in vascularized oromandibular reconstruction. AB - Sixty cases (59 patients) of oromandibular reconstruction using vascularized iliac crests were compared with 13 in which radial osteocutaneous flaps were used. These patients were reviewed from the standpoint of cosmetic results and function as well as their operative and postoperative courses. In both groups, the results were generally good. However, revisionary surgery was more frequent in those receiving the iliac crest. This group also had a higher incidence of intraoral wound breakdown and bone exposure. Nevertheless, the sheer size of the iliac crest made it ideal for massive oromandibular defects, just as its natural curvature lent itself to precise replication of the mandible in bone-only reconstructions. Its bulk proved a major obstacle in small composite defects. The radial forearm flap carried thin, pliable, well-vascularized skin that was superior to groin skin for oral lining. Bone gaps of up to 9 cm could be handled with ease, thus making it complementary to the iliac crest over the wide spectrum of mandibular reconstruction. PMID- 2305938 TI - APACHE II in emergency operations for perforated ulcers. AB - Most reports concerning the management of patients with perforated peptic ulcers suffer from inadequate documentation of the severity of illness and the operative risk of these patients. This study attempts to evaluate the prognostic value of the APACHE II scoring system in a homogeneous group of patients with perforated peptide ulcers, to assess it as a potential clinical and research tool for future studies, and to examine its usefulness in stratifying these patients according to their surgical risk. Our results confirm the prognostic value of the APACHE II scoring system, measured either retrospectively or prospectively, in patients who undergo emergency operations for perforated ulcers. When measured preoperatively, it accurately stratifies these patients to various risk groups and should therefore be used in future trials examining various treatment aspects of this condition. Our data, evaluating the results of various procedures in subgroups of patients stratified by the APACHE II, failed to support the superiority of one approach over another. PMID- 2305939 TI - Intraoperative tissue oximetry in the human gastrointestinal tract. AB - Tissue oxygen tension was measured using a modified Clark oxygen electrode in the gastrointestinal tract of 33 patients undergoing laparatomy. The electrode, which incorporated a thermistor, had a linear response to oxygen tension (r = 0.995, p less than 0.001). The patients were all maintained on an inspired oxygen concentration of 33 +/- 3% and had a mean arterial oxygen tension (PaO2) of 124.9 +/- 31.9 mm Hg. Tissue oxygen tension measurements (mm Hg, mean +/- SD) were recorded from the serosal surfaces of the stomach (46.3 +/- 15.4), mid-ileum (36 +/- 9.7), terminal ileum (33.5 +/- 11.5), cecum (30.3 +/- 7.4), transverse colon (38.5 +/- 10), descending colon (29.3 +/- 11), and sigmoid colon (39.2 +/- 7.7) and tended to increase with increasing PaO2 (r = 0.70, p less than 0.001). Arterial occlusion resulted in a gradual decrease in tissue oxygen tension. It is concluded that intraoperative tissue oxygen tension measurement is feasible, and that the technique may have clinical applications in the assessment of intestinal viability. PMID- 2305940 TI - Elective surgery without transfusion: influence of preoperative hemoglobin level and blood loss on mortality. AB - To clarify the widespread practice of preoperative transfusion to attain a 10 g/dL level of hemoglobin, the relationship between preoperative hemoglobin level, operative blood loss, and mortality was studied by analyzing the results of 113 operations in 107 consecutive Jehovah's Witness patients who underwent major elective surgery. Ninety-three patients had preoperative hemoglobin values greater than 10 g/dL; 20 had preoperative hemoglobin levels between 6 to 10 g/dL. Mortality for preoperative hemoglobin levels greater than 10 g/dL was 3 of 93 (3.2%); for preoperative hemoglobin levels between 6 to 10 g/dL, mortality was 1 of 20 (5%). Mortality was significantly increased with an estimated blood loss of greater than 500 mL, regardless of the preoperative hemoglobin level (p less than 0.025). More importantly, there was no mortality if estimated blood loss was less than 500 mL, regardless of the preoperative hemoglobin level. From these data, we conclude that: (1) Mortality in elective surgery appears to depend more on estimated blood loss than on preoperative hemoglobin levels; and (2) Elective surgery can be done safely in patients with a preoperative hemoglobin level as low as 6 g/dL if estimated blood loss is kept below 500 mL. PMID- 2305941 TI - Comparison of portal vein chemotherapy with hepatic artery chemotherapy in the treatment of liver micrometastases. AB - This study was conducted in a rat model of hepatic micrometastases generated by the intraportal injection of a colonic carcinoma cell line bound to polystyrene microspheres. Thirty-two animals received continuous infusions of 5-fluorouracil (5-FU) into either the portal vein or hepatic artery for a period of 7 days. Drug infusions were begun at 0, 2, 4, and 6 days after the time of tumor inoculation in four groups of animals, respectively. Subsequent tumor growth in these animals at 1 month was compared with tumor growth in 11 control animals that did not receive chemotherapy. When 5-FU was administered via the portal vein on the same day as tumor inoculation, liver metastases were reduced by approximately 91% (p = 0.004). Portal vein chemotherapy administered 6 days after tumor inoculation, when macroscopic nodules had a mean diameter of 0.33 +/- 0.03 mm (SE), produced no tumor response (p = 0.36). Histologic examination of these lesions revealed early invasion outside distended portal venules. In contrast, hepatic artery 5-FU infusions administered at 0, 2, 4, and 6 days after tumor implantation all reduced the subsequent development of hepatic metastases by approximately two thirds of that observed in the untreated group (p = 0.004). We conclude that hepatic artery chemotherapy may have an important complementary role to play as an adjuvant treatment for gastrointestinal cancer. PMID- 2305942 TI - Clinical application of a new compression anastomotic device for colorectal surgery. AB - Fifty-six patients underwent large bowel anastomosis by the compression anastomotic device developed by the authors from May 1986 through December 1988. Operations performed were 40 left hemicolectomies or anterior resections of the sigmoid and rectum, 7 left colon resections, 7 right hemicolectomies, and 2 total colectomies. Twenty-one anastomoses were done on the extraperitoneal rectum, in 7 cases less than 4 cm from the anal verge and in 9 cases between 4.5 and 8 cm. Five intraoperative diverting colostomies were done (9%). The rings of the device were evacuated postoperatively after a mean of 11 days with little or no discomfort. Operative mortality was 1.8% (one patient died of myocardial infarction). Anastomotic complications were one (1.8%) clinical and one (1.8%) subclinical leak. Mean postoperative hospital stay was 14 days. This initial clinical experience shows that the anastomotic device is reliable. PMID- 2305943 TI - Mobilization of the right lobe of the liver for right adrenalectomy. AB - Exposure of the right adrenal gland can be a problem with a transabdominal approach because of the overlying liver. The usual method of handling the liver to gain access to the right adrenal gland is to retract the liver superiorly and laterally, but when the right adrenal gland or tumor within it is high lying, exposure may be inadequate. In this situation, mobilization of the right lobe of the liver will provide direct access to the right adrenal gland and vein. PMID- 2305944 TI - Securing endotracheal tubes in patients with facial burns or trauma. AB - Securing an endotracheal tube on patients with facial burns or trauma can pose difficulties. A nasotracheal support splint, made of materials commonly used by occupational therapists, can facilitate safe anchoring of a nasotracheal tube. PMID- 2305945 TI - Surgery interns' experience with surgical procedures as medical students. AB - Instruction in the technical aspects of surgery begins in medical school. To identify areas of inexperience among incoming interns, we asked 40 first-year residents to indicate which bedside and emergency room procedures and operations (or parts of operations) they had performed in medical school and to rate how confident they were in performing those procedures as a result of their experiences. Respondents indicated that placement of nasogastric tubes, Foley catheters, and central lines were procedures they commonly performed (78.4% to 97.3%); they less frequently placed arterial and pulmonary arterial lines and chest tubes (21.6% to 64.9%). Many students had opportunities to assist in closure of incisions in actual operations (60%), but only 22% performed other parts of operative procedures. Opportunities to perform procedures did not correlate with the length of time spent on surgical rotations. Nearly half (49%) participated in animal surgery laboratories as part of their surgical rotation. These findings suggest that many interns have not performed some basic procedures by the time they enter their residency. Instruction in technical skills in clinical medicine, frequently surgical, represents a deficiency in medical school curricula. The general inexperience of surgical interns in performing these procedures must be remembered when assigning these duties. PMID- 2305946 TI - My constant quest to maintain my procedural skills. PMID- 2305947 TI - [Continuous measurement of cardiac output based on the Fick principle in cardiac anesthesia]. AB - With the development of fiberoptic and pulse oximetry, as well as the development of the more modern methods of oxygen consumption measurements, the online monitoring of Fick cardiac (FCO) output has become possible in the clinical treatment routine. The aim of this study was to compare fiberoptically measured mixed venous oxygen saturation with values from blood samples and continuously determined Fick cardiac output with intermittent thermodilution cardiac output (TCO). Ten patients undergoing coronary artery bypass grafting were measured during the perioperative period. Total body oxygen consumption was determined with a metabolic monitor (Deltatrac Datex) from respiratory gases. Arterial oxygen saturation was assessed by pulse oximetry (Nellcor). Mixed venous oxygen saturation was measured by a balloon tipped pulmonary artery fiberoptic catheter (Opticath) attached to an electronic device based on three wavelengths (Oximetrix cardiac output monitor). Hemoglobin, Methemoglobin and CO-hemoglobin were determined from intermittent blood samples by in vitro analysis. FCO was calculated from corresponding differences in arterial mixed venous oxygen and total body oxygen consumption. TDCO values were calculated from microcomputer recordings of the thermodilution data by monoexponential curve-fitting with respect to baseline drift. A significant systematic difference between FCO and TCO was observed. FCO exceeded TCO on average by 0.42 +/- 0.12 l/min. The limits of confidence (95%) were 0.18 to 0.66 l/min. There was no systematic difference between mixed venous saturation measurements with the fiberoptic system and from blood samples. The cardiac output values derived from fiberoptic and pulse oximetry can be considered sufficiently reliable for clinical purposes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305948 TI - [Intraoperative suppression of spasticity using intrathecal baclofen]. AB - Even in patients with complete loss of sensation and paraplegia after cervical spinal trauma, abdominal operations usually require general or spinal anesthesia due to spasms and increased muscle tone. Both anesthetic types have serious drawbacks under these circumstances, e.g. hyperkalemia induced by relaxation or the impossibility of adequate monitoring of the level of spinal blockade. After an onset time of 1-2 h the intrathecal injection of approx. 100 micrograms baclofen, a spinally acting GABAB-agonist, led to complete and long-lasting suppression of surgically induced spasticity. This could be demonstrated by neurological examination (spasticity scores: Ashworth score, spasm score, clonus score) during 5 neurosurgical operations in 3 patients with paraplegia. Except for slight sedation, the patients had no discomfort during operation. Intrathecal baclofen was also effective against autonomic hyperreflexia, i.e. vegetative dysregulation such as bradycardia or hypertension, provoked by catheterization or bladder surgery. PMID- 2305949 TI - [A paradoxical air embolism in a closed foramen ovale]. AB - This case report deals with a patient who was being operated on for a tumor of the colon and who died from a paradoxical venous air embolism. Accompanying massive blood loss impedes differentiation of hemodynamic disturbances either due to venous air embolism or to hemorrhage, respectively. Air was aspirated from the radial artery catheter that was used for blood-pressure monitoring and for taking blood samples for laboratory analysis. At autopsy, no probe-patent foramen ovale could be demonstrated. The mechanism of air passing from the venous to the systemic circulation in our patient remains speculative; however, mechanical cardiopulmonary reanimation itself with its underlying thoracic pump mechanism has to be considered as contributing to the transport of air from the venous to the arterial side of the circulation. PMID- 2305950 TI - [Bacterial pneumonia in ventilated patients. The role of bronchoalveolar lavage in diagnosis and therapy]. AB - In the diagnosis and treatment of bacterial pneumonia, the isolation and resistance pattern of the causative organisms are very relevant. Bronchoalveolar lavage (BAL) with quantitative culture is the best technique to obtain material for bacteriological investigations in nonintubated medical patients and in a baboon model. The present study was designed to clarify the following questions: What is the value of BAL compared to tracheal secretion (TS) in ventilated patients with regard to antibiotic therapy? Is it possible to distinguish colonization and infection by investigation of BAL? MATERIAL AND METHODS. In 34 ventilated patients, we studied the diagnostic and therapeutic value of BAL in comparison to TS. Thirteen patients suffered from pneumonia, 9 patients were colonized, and in 12 pneumonia was uncertain. These terms are defined as follows: 1. Pneumonia: temperature over 38.5 degrees C, leukocyte count over 12,000/mm3, infiltrate in the x-ray compatible with pneumonia, purulent tracheal secretion, positive bacteriological findings. All criteria must be fulfilled. 2. Colonized patients: mechanical ventilation more than 7 days, no signs of infection, isolation of the same bacteria species in two previously obtained tracheal secretions. 3. Uncertain pneumonia: not all criteria mentioned above were fulfilled. BAL was performed in the usual manner. The bronchoscope was wedged into a distal airway and 6 x 20 ml of sterile, nonbacteriostatic saline (0.9% NaCl) was instilled through the suction channel and subsequently aspirated. All investigation materials were immediately processed in the bacteriological laboratory. From the BAL specimen Giemsa and Gram preparations were performed to look for contamination from the throat and intracellular bacteria. RESULTS. Patients with pneumonia: In all patients the TS and BAL were positive. Cultures from BAL and TS were in agreement in 77% of the cases. In 10 patients intracellular bacteria (BAL) were present, in two patients the Gram preparation was nonapplicable because of destroyed cells. In one patient Haemophilus spp. could be isolated in the BAL (10(5)/ml BAL), but not in TS, which definitely influenced therapy. Colonized patients: In all patients TS and BAL were positive, with exact agreement in 33% of the cases. The concentration of isolated bacteria (BAL) was not as high in these patients as in the patients with pneumonia (median: 8 X 10(3) vs 6 X 10(4]. However BAL allowed no differentiation between colonization and infection in individual cases. Uncertain pneumonia: TS was positive in 8 patients, no TS could be obtained in 4. BAL was sterile in 4. Only in 2 bacteria greater than or equal to 10(4)/ml were isolated and both patients had intracellular bacteria. The results (BAL) influenced therapy in 5 cases (4 patients received no antibiotics; in 1 patient the antibiotics were modified). CONCLUSION. BAL is very helpful in patients suspected of having pneumonia and in sepsis of unknown origin when pneumonia should be excluded... PMID- 2305951 TI - [Indications for the insertion of a central venous catheter in emergency situations]. AB - The use of a central venous catheter (CVC) is associated with numerous complications despite its usefulness. Less experienced personnel have a higher complication rate, however complications are not totally avoidable even for more experienced persons. The complication rate increases under unfavorable working conditions. Therefore, the indication for a CVC even in the emergency situation must be considered very carefully. PMID- 2305952 TI - [Chemical compatibility of ketamine and midazolam in infusion solutions]. AB - The chemical compatibilities of intravenous (i.v.) solutions containing ketamine and midazolam were investigated by UV/VIS spectroscopy, IR spectroscopy, and high performance liquid chromatography (HPLC). The isotonic solutions used were NaCl 0.9%, fructose 5%, and glucose 5%. The concentrations of additives were 500 mg ketamine and 45 mg midazolam per liter i.v. solution. Comparison of the UV/VIS and IR spectroscopic measurements with spectra from the literature demonstrated, that the substances were pure, e.g. without larger impurities. The HPLC measurements were performed immediately after preparation of the solution and repeated after 6, 25, 50, 75 and 97 h. It was shown that there was no concentration decrease of ketamine and midazolam in the i.v. solutions within an experimental error of 1.5% and within 100 h. Reactions in the i.v. solutions with smaller than 1.5% conversion can not be excluded. We recommend that the prepared i.v. solution be used within 24 h. PMID- 2305953 TI - [A universally applicable mask attachment for fiberoptic intubation. The Mainz Universal Adapter]. AB - The problems associated with "difficult airways" have almost subsided since the introduction of flexible fiberoptic bronchoscopes for tracheal intubation. Limitations of this technique persist with uncooperative patients, children and infants. We describe an universally applicable connector for fiberoptic intubation during mask ventilation, which fits all masks with a 22-mm connector, including the Rendell-Baker-Soucek type. This technique is of utmost value when a "difficult airway" is encountered only subsequent to induction of anesthesia, especially if nondepolarizing muscle relaxants have been administered. The device makes intubation possible with all sizes of fiberoptic bronchoscopes. The prerequisites for application of this technique include an airway that will be maintained by mask ventilation. PMID- 2305954 TI - Accuracy of peak deconvolution algorithms within chromatographic integrators. AB - The soundness of present-day algorithms to deconvolve overlapping skewed peaks was investigated. From simulated studies based on the exponentially modified Gaussian model (EMG), chromatographic peak area inaccuracies for unresolved peaks are presented for the two deconvolution methods, the tangent skim and the perpendicular drop method. These inherent inaccuracies, in many cases exceeding 50%, are much greater than those calculated from ideal Gaussian profiles. Multiple linear regression (MLR) was used to build models that predict the relative error for either peak deconvolution method. MLR also provided a means for determining influential independent variables, defining the required chromatographic relationships needed for prediction. Once forecasted errors for both methods are calculated, selection of either peak deconvolution method can be made by minimum errors. These selection boundaries are contrasted to method selection criteria of present data systems' algorithms. PMID- 2305955 TI - Adaptation of a thermospray liquid chromatography/mass spectrometry interface for use with alkaline anion exchange liquid chromatography of carbohydrates. AB - An interface is described that allows the direct coupling of high-performance alkaline anion exchange liquid chromatography with thermospray mass spectrometry. A membrane suppressor is used to remove nonvolatile alkaline salts from the mobile phase after the chromatographic process is completed and prior to introduction into the mass spectrometer. Examples are given of both isocratic and gradient separations of a three-component test mixture of N-acetylated mono- and disaccharides, followed by on-line mass spectral data acquisition. Sensitivity studies show minimum detection limits for the test compounds to be in the microgram range. PMID- 2305956 TI - Cross-linked redox gels containing glucose oxidase for amperometric biosensor applications. AB - Oxidoreductases, such as glucose oxidase, can be electrically "wired" to electrodes by electrostatic complexing or by covalent binding of redox polymers so that the electrons flow from the enzyme, through the polymer, to the electrode. We describe two materials for amperometric biosensors based on a cross linkable poly(vinylpyridine) complex of [Os-(bpy)2Cl]+2+ that communicates electrically with flavin adenine dinucleotide redox centers of enzymes such as glucose oxidase. The uncomplexed pyridines of the poly(vinylpyridine) are quaternized with two types of groups, one promoting hydrophilicity (2 bromoethanol or 3-bromopropionic acid), the other containing an active ester (N hydroxysuccinimide) that forms amide bonds with both lysines on the enzyme surface and with an added polyamine cross-linking agent (triethylenetetraamine, trien). In the presence of glucose oxidase and trien this polymer forms rugged, cross-linked, electroactive films on the surface of electrodes, thereby eliminating the requirement for a membrane for containing the enzyme and redox couple. The glucose response time of the resulting electrodes is less than 10 s. The glucose response under N2 shows an apparent Michaelis constant, Km' = 7.3 mM, and limiting current densities, jmax, between 100 and 800 microA/cm2. Currents are decreased by 30-50% in air-saturated solutions because of competition between O2 and the Os(III) complex for electrons from the reduced enzyme. Rotating ring desk experiments in air-saturated solutions containing 10 mM glucose show that about 20% of the active enzyme is electrooxidized via the Os(III) complex, while the rest is oxidized by O2. These results suggest that only part of the active enzyme is in electrical contact with the electrode. PMID- 2305957 TI - Simulation of two-electron homogeneous electrocatalysis for steady-state voltammetry at hemispherical microelectrodes. AB - Expanded space grid digital simulation of second-order, two-electron homogeneous electrocatalysis was extended to slow scan voltammetry at hemispherical microelectrodes. Predictions of the simulations are examined for reversible and quasireversible heterogeneous charge transfer of catalyst for a range of homogeneous catalytic rate constants (k1) and electrode radii. Working curves of catalytic efficiency vs long k1 were generated assuming reacting species with equal diffusion coefficients. As electrode radii in the less than 10-microns range decrease, progressively larger homogeneous catalytic rates are needed to yield analytically significant amplification of limiting currents. Simulations using hemispherical radii of (2/pi)rd can be used to predict catalytic efficiencies for microdisk electrodes with radii rd. Simulated working curves were used to estimate a log k1 of 3.88 +/- 0.55 (M-1 s-1) for electron transfer from the anion radical of 9,10-diphenylanthracene to 4,4'-dibromobiphenyl from steady-state catalytic efficiencies obtained at carbon microdisk electrodes. This value was in good agreement with 3.90 +/- 0.16 M-1 s-1 found previously by cyclic voltammetry. PMID- 2305958 TI - Differentiation of leucine and isoleucine residues in peptides by consecutive reaction mass spectrometry. PMID- 2305960 TI - [Growth of the heart in Brazilian fetuses]. AB - The growth of the heart was studied in 59 Brazilian fetuses by the allometric method (log y = k log x + log b). The mass of the heart (WH, log y) was correlationed with the parameters of the fetus (log x) as body mass (BM), crown rump length and gestational age. The WH increases in an isometric way with the BM. However, the WH increases in an allometric way with the other parameters. The equations and graphics presented in this work were determined by the first time in the literature to the Brazilian fetuses. PMID- 2305959 TI - Polishable and robust biological electrode surfaces. PMID- 2305961 TI - Anatomic data of the human coronary sinus. AB - The authors studied the formation, tributaries, length and the ostium of the coronary sinus, as well as the relationship of the venous walls to the myocardium and to the epicardium. The observations were made out of 143 hearts of subjects of different ages, and it was found that the most frequent display of the coronary sinus valve was a semilunar form (52 adults, 15 youngsters, 2 children, 3 newborn); it was also found valves in a cribriform or septal form. The absence of the valve of coronary sinus was noted in 53 cases (42 adults, 9 youngsters, 2 newborn). The valve of Vieussens was found, in some cases, at the level of the transition between the great cardiac vein and the coronary sinus, as well as others single or double parietal venous valves. The action of the valve of coronary sinus is also discussed by the authors. PMID- 2305962 TI - Morphological changes in some endocrine organs in rats following chronic lithium treatment. AB - Chronic prophylactic administration of lithium, a well-known anti-manic drug, has been reported to have a wide number of potential side effects involving metabolic, reproductive and endocrine systems. Since most of the existing literature reports on biochemical changes, the present investigations were undertaken to examine whether chronic lithium treatment could lead to morphological alterations in various endocrine organs. Sexually adult male Fischer rats, acclimatized to standardized laboratory conditions of light (LD 14:10) and temperature (21-23 degrees C) for 2 weeks, were treated with lithium by feeding a specially prepared chow containing 0.4% lithium chloride. The diet was administered for 15 d to one group and for 30 d to the other after which the animals were decapitated and the thyroid, adrenal, pancreas, testis and seminal vesicles were quickly dissected out and fixed in 10% neutral formalin. After routine histological procedures, 5 microns thick paraffin sections were stained by hematoxylin-eosin or Gomori's trichrome stain and examined under light microscope. Definitive morphological alterations were noted in the thyroid gland in that chronic lithium led to significant reduction in the epithelial height of the follicular cells and in an increase in colloidal content, suggesting a hypothyroid condition. Chronic lithium also resulted in decreased epithelial height in the seminal vesicle; the mucosal pseudostratified columnar epithelium regressed to an almost squamous epithelium. No discernible morphological changes were evident in the other endocrine glands studied. These results provide important morphological correlates and support some of the biochemical studies reported earlier on the potential adverse effects of lithium. PMID- 2305963 TI - Ultrastructure of the nephron of grey mullets (Mugil cephalus L. and Liza saliens Risso 1810). AB - Mugil cephalus and Liza saliens nephrons consist of renal corpuscles, neck segments, first, second and third proximal segments, collecting segments and collecting ducts. The glomerular endothelial cells are fenestrated showing a thin diaphragm. Mesangial cells are located around and between the capillaries, suggesting a role in vessel contraction; they show no phagocytic ultrastructural features. An extensive part of the podocyte surface lies flat on the glomerular basement membrane; this characteristic is probably related to the diminishing of the glomerular filtration rate. Podocytes show large multivesicular bodies, lysosomes and vesicles with a dense bar. Large globules in the podocytes point to their possible secretory activity. The first proximal segment is made up of principal cells with a well developed brush border and tightly packed basal infoldings, and scarce ciliated cells. The second proximal segment consists of principal cells, with loose-packed microvilli and numerous deep basal invaginations, ciliated cells and dark cells. The third proximal segment shows cells with irregularly arranged microvilli and a basal labyrinth, and some ciliated cell. The collecting segment and the collecting duct cells were characterized by apical mucous droplets; the latter also show a well developed basal labyrinth and are surrounded by a layer of smooth muscle cells. PMID- 2305964 TI - Topography and cytoarchitectonics of small-cell nuclei of the tuber cinereum in Insectivora. AB - Results are presented of the comparative studies on location and cytoarchitectonics of the nuclei in tuber cinereum of hypothalamus in 3 insectivorous mammals: hedgehog, mole and common shrew. Paraffin scraps were stained with the methods of Nissl and Kluver-Barrera. It was found that this part of the brain in Insectivora was characterized by: well developed nucleus infundibularis, less developed nucleus dorsomedialis compared to nucleus ventromedialis, weakly pronounced differentiation of the periventricular part, and lack of nucleus tuberis lateralis. From among the Insectivora under study, cytoarchitectonics of tuber cinereum in mole and common shrew was more or less similar, while it differed from that of hedgehog, in which nucleus dorsomedialis and nucleus hypothalamicus parvocellularis were less developed, nucleus ventromedialis was different, and so was cell structure of nucleus infundibularis. PMID- 2305965 TI - An ultrastructural study of development of the leptomeninx of the rabbit spinal cord. AB - Development of the rabbit spinal cord leptomeninges was examined in embryos and fetuses aged 12 to 30 d post-conception. In the early stages of development all mesenchymal cells surrounding the neural tube were structurally similar, resembling immature fibroblasts. At 16 d post-conception cells adjacent to the glia limitans showed little structural change, apart from an increase in the amount of rough endoplasmic reticulum, but cells in the presumptive arachnoid became packed with glycogen. By E22 glycogen was present in pial cells but never in the amounts found in the arachnoid. As development proceeded the amount of glycogen in the leptomeninges declined. Pial collagen increased both in amount and in fibre diameter with age. PMID- 2305966 TI - Craniofacial and limb development in early rat embryos following in utero exposure to ethanol and caffeine. AB - Alcohol and caffeine are widely consumed. Their combined effects on the early morphogenesis of the craniofacial region and limbs were investigated in the rat. The most common developmental defects included reduction in the number of branchial bars and somites, as well as an impairment in the formation of the forelimb bud. PMID- 2305967 TI - Afferent connections of the prelunate visual association cortex (areas V4 and DP). AB - The afferent and efferent connections of the prelunate visual association area V4 of macaque monkeys were investigated by means of the horseradish peroxidase (HRP) method. The specific thalamic afferents from the dorsolateral segment of the medial pulvinar and the lateral segment of the inferior pulvinar were topographically organized. A band of cells was labelled in the intralaminar nuclei (nucl. centr. med. and lat., reaching into LD and the most dorsal part of VL), and a few cells in the interlaminar layers of the lateral geniculate body. Other diencephalic afferents included the claustrum, the nucleus basalis Meynert and the pars compacta of the substantia nigra. Ipsilateral cortical areas which projected into V4 included area 18 (V2), the inferior parietal cortex, the anterior and posterior parts of the superior temporal sulcus, the frontal eye fields and the temporo-basal association cortex on the lateral half of the parahippocampal gyrus and around the occipito-temporal sulcus. In the contralateral cortex, discontinuous regions in areas V4 and V5 on the prelunate gyrus and some cells at the 17/18-border were labelled. All regions in which labelled cells were found and, in addition a restricted region in the dorsal cap of the head and the tail of the caudate nucleus showed fibre and terminal labelling. In addition mesencephalic afferents and efferents were identified but not investigated in detail. An attempt to estimate the quantitative contribution of the various afferent systems to the prelunate cortex was made by counting the labelled cells in the different areas. The afferent and efferent organization of the prelunate visual association area indicates that it is incorporated in a network of cortical and subcortical regions involved in various aspects of visual behavior. PMID- 2305968 TI - Continuum analysis of common branching patterns in the human arch of the aorta. AB - A model is proposed for describing common variations in the arrangement of branches on the arch of the human aorta, and the model is used to analyze data from 123 human arches. The analysis allows the observed variations to fall freely along a continuous spectrum, rather than be confined to discrete categories as is commonly done at present. The results thus describe these variations in a more natural way and throw some new light on their likely source. PMID- 2305969 TI - Optic nerves in plethodontid salamanders (amphibia, urodela): neuroglia, fiber spectrum and myelination. AB - In five species of lungless salamanders, family Plethodontidae, which all show highly developed visual abilities, the ultrastructure of the optic nerve was investigated and the total number of retinal ganglion cell axons, the percentage of myelinated axons, and the volume densities of glia and axons were determined. More than 80% of all axons were smaller than 0.4 micron and only 2-3% were larger than 0.8 micron. In individual nerves the degree of myelination varied between 1 and 9% which is in the range reported for other amphibian species. The miniaturized and highly paedomorphic species Batrachoseps attenuatus was an exception because only very few or even no myelinated axons were present in the nerve, which is unique among gnathostome vertebrates. The five investigated species had total numbers of axons ranging from 26,000 in Batrachoseps attenuatus to about 50,000 in Plethodon jordani. These numbers are the lowest found among vertebrates with an elaborated visual system. The amount of glial material in the optic nerve varied between 25 and 50%, with larger nerves possessing more glia than smaller ones. Ultrastructural analysis revealed that the optic nerve of each species contained both astrocytes and oligodendrocytes, although often in immature form. In Batrachoseps attenuatus the glia showed features of both astrocytes and oligodendrocytes which reflect an undifferentiated state. PMID- 2305971 TI - An ultrastructural study of early chorionic villus formation in the marmoset monkey (Callithrix jacchus). AB - The ultrastructural morphology of developing chorionic villi in the marmoset monkey (Callithrix jacchus) placenta was studied in pregnant monkeys at known time intervals after ovulation. In samples obtained at 45 days after ovulation the mesoderm, which consists of primitive foetal blood vessels, is seen to extend down into cytotrophoblast columns. Syncytiotrophoblast completely surrounds maternal blood vessels and both basal laminae and endothelial cells of maternal origin show signs of disorganisation and degradation. Syncytiotrophoblast is first observed to breach the maternal circulation in samples collected from animals at 60 days after ovulation; this results in discrete haemochorial villi randomly distributed throughout the placental bed. Samples obtained at 80 days after ovulation and term placental samples (145 days after ovulation) exhibit tertiary haemochorial villi throughout the placenta, similar to those seen randomly distributed at 60 days after ovulation. PMID- 2305970 TI - Neural tube formation in the mouse: a morphometric and computerized three dimensional reconstruction study of the relationship between apical constriction of neuroepithelial cells and the shape of the neuroepithelium. AB - Morphometry and computerized three-dimensional reconstruction were used to study the relationship between apical constriction of neuroepithelial cells and the pattern of bending of the neuroepithelium in the developing neural tube of the 12 somite mouse embryo. The neuroepithelium of the mouse exhibits prominent regional variations in size and shape along the embryo axis. The complex shape of most of the cephalic neural tube (e.g., forebrain and midbrain) is due to the coexistence of concave and convex bending sites whereas more caudal regions (e.g., hindbrain and spinal cord) generally lack sites of convex bending and have a relatively simple shape. The apical morphology of neuroepithelial cells was found to be correlated more closely with the local status of bending of the neuroepithelium than with the specific region of the neural tube in which they are located. In areas of enhanced apical constriction, microfilament bundles were particularly prominent. Morphometry revealed that patterns of bending of the neuroepithelium were correlated almost exactly with those of apical constriction throughout the forming neural tube. These findings support the idea that apical constriction of neuroepithelial cells, resulting from tension generated by microfilament bundles, plays a major role in bending of the neuroepithelium during neural tube formation in the mouse. PMID- 2305972 TI - A study of the morphology of the gills of an extreme alkalinity and hyperosmotic adapted teleost Oreochromis alcalicus grahami (Boulenger) with particular emphasis on the ultrastructure of the chloride cells and their modifications with water dilution. A SEM and TEM study. AB - The general gill morphology of Oreochromis alcalicus grahami, a teleost adapted to high salinity and hyperosmosis, is basically similar to that of other teleostean fish. The species has four pairs of gill arches, all of which have well developed filaments. Each of the arches (holobranchs) has two rows of filaments (hemibranchs). Bilaterally situated secondary lamellae branch from the central axis of the filaments. The lamellae reach their maximum size at the middle of the filament, gradually decrease in size and eventually disappear towards the tip of the filament, which is bare. The leading edge of the gill filament and the immediate interlamellar space is covered by a stratified epithelium consisting of pavement cells, mucous cells, chloride cells and undifferentiated cells. The surface of these cells is made up of concentric microridges. The chloride cells were found only on the primary epithelium (filamental epithelium) and very rarely on the secondary epithelium (lamellar epithelium). Two types of chloride cells were observed in the gills of Oreochromis. The superficial chloride cells have fewer mitochondria concentrated towards the basal aspect of the cell, and a network of tubules towards the apical surface and are less electron dense. These cells intercommunicate with the water through an apical pore. The deep chloride cells have numerous diffuse mitochondria intercalated between a fine profuse tubular network and are more electron dense. These cells are covered by one or more layers of pavement cells and thus do not have access to the external surface. After gradual dilution of the lake water in which the fish were kept, both types of chloride cells remained topographically and ultrastructurally distinct. However, in both kinds of cell the mitochondria decreased in number and size. Initially there was an increase in the diameter and the degree of interdigitation of the tubules followed by a gradual decrease. An increase in the quantity of rough endoplasmic reticulum, particularly at the perinuclear region of the cell, was noted. The morphometric analysis of the branchial system indicated that the gills of Oreochromis are well adapted for gas exchange by having numerous and relatively long gill filaments with a high lamellar density. These features provide a large surface for gas exchange which, when coupled with the notably thin water-blood barrier of an average thickness of only 0.83 micro, would facilitate efficient absorption of oxygen by the gills. Oreochromis alcalicus was observed to be incapable of adapting to freshwater. This may have been due to the progressive degeneration of the chloride cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2305973 TI - Observational studies and predictive models. PMID- 2305974 TI - Angina and other risk factors in patients with cardiac diseases undergoing noncardiac operations. AB - Six hundred eighty-eight consecutive patients with cardiac diseases or who were older than 70 yr of age, all of whom were undergoing noncardiac operations, were studied. Twenty-four preoperative risk factors were analyzed for the outcome of perioperative myocardial infarction (PMI) or cardiac death using stepwise logistic regression. Old age, emergency operation, angina, previous myocardial infarction, electrocardiographic signs of ischemia, type of surgical procedure, and hypokalemia were identified as individual factors useful in predicting outcome. Thirty-two patients (4.65%) developed PMI. Seven of these 32 patients (21.9%) and eight more patients without PMI--a total of 15 patients (2.2%)--died a cardiac death. Nonfatal but serious complications occurred in 23% of the patients. Patients undergoing emergency operations and patients with chronic stable angina, previous myocardial infarction, and electrocardiographic signs of ischemia were found to be at increased risk for PMI and cardiac death. PMID- 2305975 TI - Azumolene reverses episodes of malignant hyperthermia in susceptible swine. AB - Azumolene is an analogue of dantrolene with much greater water solubility. Ten swine susceptible to malignant hyperthermia (MH) were triggered into MH episodes via the inhalation of halothane, and azumolene was effective in terminating all of the MH episodes. There was an inverse relationship between the dose of azumolene required to terminate the MH episode and the time it took for the pig to manifest the signs of MH. Azumolene was found to be similar in potency to dantrolene. PMID- 2305976 TI - Comparison of patient-controlled epidural analgesia and conventional intermittent "top-up" injections during labor. AB - In a prospective, randomized manner, bolus injection patient-controlled epidural analgesia (PCEA; n = 30) and conventional intermittent "top-up" injections (CIT; n = 28) of bupivacaine in nulliparous parturients during first stage of labor were compared. Group A (PCEA) patients self-administered, using a patient controlled analgesia device, 4-mL increments of 0.125% bupivacaine with 1: 400,000 epinephrine, to a maximum 12 mL/h as required. Group B (CIT) patients received 12 mL of the same solution, on request, from the anesthesiologist. Hourly assessments of pain relief (visual analogue scale), satisfaction, sensory and motor block, blood pressure, and cervical dilatation were made. In addition, retrospective pain assessments were made in patients requesting analgesia in the preceding hour, indicating their maximum pain during that time. The groups were demographically comparable and equally low hourly bupivacaine requirements were seen (group A, 6.36 +/- 0.43 mg; group B, 6.23 +/- 0.39 mg) producing similar mean sensory levels. Pain relief obtained in both groups was similar but was associated with greater satisfaction in patients using PCEA (P less than 0.05). This study shows that PCEA is a viable alternative for providing pain relief in the first stage of labor. PMID- 2305977 TI - Pharmacokinetics of ropivacaine in nonpregnant and pregnant ewes. AB - The pharmacokinetics of ropivacaine were studied in chronically instrumented nonpregnant and pregnant ewes. On the day of study, the urinary bladder was catheterized. Ropivacaine (2.5 or 3.0 mg/kg) was administered by intravenous infusion over 2 or 4 min. Serial samples of arterial blood and urine were collected over 5 h, and drug concentrations were determined using a gas chromatographic technique. Total clearance of ropivacaine was lower in the pregnant animals (21.6 +/- 4.5 mL.min-1.kg-1) compared with the nonpregnant animals (45.1 +/- 6.7 mL.min-1.kg-1). There was a tendency toward a decrease in the volume of distribution during the terminal exponential phase of drug elimination of 2.03 +/- 0.36 L/kg in the pregnant and 4.32 +/- 1.03 L/kg in the nonpregnant sheep. Thus the difference in the elimination half-life was only minimal: 74.7 +/- 10.7 min in the pregnant and 64.4 +/- 7.4 min in the nonpregnant animals. It is concluded that ovine pregnancy is accompanied by changes in the pharmacokinetics of ropivacaine. Inadvertent intravenous injections of similar drug doses to pregnant and nonpregnant women might result in higher plasma concentrations of ropivacaine in the former. However, the rate of decline in plasma levels of the drug would be similar in both. PMID- 2305978 TI - Effects of thiobarbiturates on smooth muscle reactivity in isolated aortas from spontaneously hypertensive rats. AB - The direct effects of thiobarbiturates on helical strips of aortas from spontaneously hypertensive (SH) rats were compared with those from Wistar-Kyoto (WKY) rats. At 5-6 wk of age, the arterial pressure of SH and WKY rats did not differ, and the effects of thiobarbiturates on aortic strips from SH and WKY rats were similar. By contrast, at the age of 10-12 or 20-21 wk arterial pressure was higher in SH than in WKY rats, and responses to thiobarbiturates differed in aortic strips from SH and WKY rats: contractile responses were greater in WKY than in SH rats, and relaxing effects were greater in SH than in WKY rats. Responses to sodium nitroprusside did not differ in the aortas of SH and WKY rats, but the effects of nifedipine were greater in strips from SH rats than from WKY rats at the age of 10-12 wk. Ca2(+)-induced contractions of strips exposed to Ca2(+)-free media and depolarized by high K+ were inhibited by treatment with thiamylal; the inhibition was greater in SH than in WKY rats. The increase in smooth-muscle relaxation induced by thiobarbiturates in strips from SH rats may be due to increased sensitivity to the Ca2(+)-channel blocking action of thiobarbiturates. PMID- 2305979 TI - Rate of change of somatosensory evoked potentials during isoflurane anesthesia in newborn piglets. AB - Most studies of the effects of inhalation anesthetics on somatosensory evoked potentials (SSEPs) have examined SSEP at single times after initiation of an anesthetic. This study describes SSEP changes as functions of time of exposure to isoflurane. Both transient and sustained SSEP changes were observed. Nonlinear regression was used to fit exponential terms to the trend curves for end-tidal anesthetic concentration and SSEP peak latency. End-tidal concentrations could be well described by two exponential terms, one with a long and one with a short time constant. Isoflurane at 1% inspired concentration produced a sustained SSEP latency change that could be fit by a single exponential term; the time constant was essentially identical to the long time constant of end-tidal concentration. The long time constants ranged from 7 to 33 min. At 0.5% isoflurane, SSEP changes were often small or not sustained, and the changes could not always be well described by an exponential curve. These data suggest that the time-course of anesthetic effects on SSEPs may be prolonged and complex, and the possibility of changes over time should be considered both in experimental studies and during intra-operative monitoring. PMID- 2305980 TI - Enhancement of fentanyl analgesia by clonidine plus verapamil in rats. AB - An investigation was made of the analgesic effects of the subcutaneous coadministration of fentanyl, an opioid mu-agonist (15 micrograms/kg), clonidine, an alpha 2-agonist (100 micrograms/kg), and verapamil, a calcium channel blocker (10 mg/kg) in rats. Nociceptive sensitivity was assessed with hot-plate and tail flick techniques. None of the three drugs alone was associated with appreciable analgesic effects in the doses used. The simultaneous administration of the three drugs resulted in marked analgesia superior to that of all binary combinations of these drugs. Two-way analysis of variance showed statistically significant differences in hot-plate and tail-flick latencies after drug treatments (P less than 0.001). The significant differences in the area under the time-response curve values (P less than 0.001) might indicate not only an increased analgesic effect, but also a prolongation of antinociception. These results suggest the existence of hitherto unreported interactions between drugs involved in the production of analgesia. PMID- 2305981 TI - Hyperbaric nitrous oxide as a sole anesthetic agent in humans. AB - Nitrous oxide (N2O) has been used to produce analgesia and anesthesia for more than 100 yr. However, because of its high MAC value (1.04), general anesthesia with N2O can usually be attained only in a hyperbaric environment. Because of the sparsity of documentation for human physiologic responses to hyperbaric N2O, we studied eight male volunteers at 2 ATA (1520 mm Hg) anesthetized with N2O only for periods of 2-4 h. N2O partial pressures ranged from 836 to 1368 mm Hg. The anesthetic state was associated with tachypnea, tachycardia, increases in systemic blood pressure, mydriasis, diaphoresis, and at times, clonus and opisthotonus. A stable level of physiologic activity was difficult to maintain. PMID- 2305982 TI - Continuous in vivo measurement of hepatic lipoperoxidation using chemiluminescence: halothane and chloroform compared. AB - Hepatic necrosis, rarely occurring after administration of modern halogenated general anesthetics, has been ascribed to free radical-induced lipoperoxidation. As evaluation of hepatic chemiluminescence has been shown to provide a noninvasive assay for oxidative radical reactions, we have made continuous in vivo measurements of hepatic light output in the phenobarbital-induced halothane anesthetized rat and compared them with observations made during chloroform anesthesia. Chloroform produced a far more rapid and more profound increase in chemiluminescence, a phenomenon probably related to depletion of hepatic glutathione. These findings are consistent with significant differences in hepatic pathology associated with the two agents. PMID- 2305983 TI - Continuous alfentanil infusion for extracorporeal shock wave lithotripsy of gallbladder stones. AB - Extracorporeal shock wave lithotripsy has recently been introduced in clinical trials for the treatment of cholelithiasis. General anesthesia, epidural anesthesia, and intravenous opiates have been used in the anesthetic management of patients undergoing this procedure. This report details our anesthetic management, which was used in 23 patients who underwent 27 procedures, and presents three illustrative cases. A continuous infusion of alfentanil and a 0.625-2.5-mg dose of droperidol were administered to the patients who were easily arousable during the procedure, and were able to cooperate with positioning change requests. Our patients did not develop apnea, hemodynamically significant bradycardia, or chest wall rigidity. One patient became nauseated, and one patient experienced a hypotensive episode that was unheralded by a change in respiratory rate, heart rate, or oxygen saturation. The patients were comfortable throughout the procedure, alert upon arrival to the postanesthesia care unit, and satisfied with this technique. A continuous infusion of alfentanil can be successfully used for the management of patients undergoing biliary lithotripsy. PMID- 2305984 TI - Differences in epidural morphine requirements between elderly and young patients after abdominal surgery. PMID- 2305985 TI - Accidental epidural narcotic overdose. PMID- 2305986 TI - Perioperative blood transfusion may conceal atypical pseudocholinesterase. PMID- 2305987 TI - Increased fluid flow through the streamline intravenous catheter. PMID- 2305988 TI - An earpiece modification to facilitate nasotracheal intubation. PMID- 2305989 TI - More about jaundice and oximetry. PMID- 2305990 TI - Restless legs during recovery from spinal anesthesia. PMID- 2305991 TI - Intravenous sedation during hepatic artery chemotherapeutic embolization. PMID- 2305992 TI - ECG changes with electroconvulsive therapy. PMID- 2305993 TI - Erroneous pulse oximeter data during CPR. PMID- 2305994 TI - A method for determining depth of unmarked endotracheal tubes used in laser surgery. PMID- 2305996 TI - Plasma lipids as a risk factor in peripheral vascular disease. AB - Plasma lipids were tested in 59 patients with symptomatic peripheral vascular disease (PVD) (confirmed by angiographic and, in many cases, operative examinations) and compared with the lipid balance in 47 nonarteriopathic subjects constituting the control group. Of all the elements considered, only the hypertriglyceridemia and the fall in the HDL cholesterol/total cholesterol ratio showed a statistically significant difference between the two groups. In particular, there was a significant difference between the two groups. In particular, there was a significant difference in the triglyceridemia present in the arteriopathic patients, as evidenced by the double check afforded by the frequency test (PVD: 25/59; control: 8/47; p less than 0.01) and the averages test (PVD: 201 +/- 131; control: 138 +/- 98; p less than 0.01). PMID- 2305995 TI - Capillary filtration and ankle edema in patients with venous hypertension treated with TTFCA. AB - The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure greater than 42 mmHg) and in a group of normal subjects before and after treatment for four weeks with Total Triterpenic fraction of Centella Asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients) was treated with TTFCA 60 mg tid; Group B (20 patients) was treated with 30 mg tid; Group C (12 patients) was treated with placebo; and Group D (10 normal subjects) was treated with TTFCA 60 mg tid in an open study. Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AECT (Ankle edema coin tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects. After four weeks of TTFCA treatment there was a significant decrease of the abnormally increased CFR, AC, and AECT time in patients. This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2305997 TI - Clinical significance of initial systolic hypertension after myocardial infarction. AB - To clarify the clinical significance of acutely raised systolic blood pressure (SBP) after myocardial infarction, 60 patients who were admitted within six hours after onset were studied. Initial systolic hypertension was shown in 26.6% of patients. Time-corresponding plasma epinephrine and norepinephrine levels were abnormally high in 61% and 86% of patients respectively. These high values of catecholamines were not, however, specific to systolic hypertension. On the contrary, an inverse correlation was observed between systolic blood pressure and plasma epinephrine value. It appeared that the anxiety and stress of chest pain do not contribute to raising blood pressure through catecholamine liberation. In the high pressure group (SBP greater than or equal to 160 mmHg), only 3 of 16 patients were classified into severer grades (III or IV) of Killip's classification. This proved to be statistically significant. A similar result was obtained in Lown's grading. Only 1 of 16 patients showed severe ventricular tachyarrhythmia. It appeared obvious from these data that patients who showed initial systolic hypertension are well protected from severe congestive heart failure and from life-threatening ventricular tachyarrhythmia in acute myocardial infarction. PMID- 2305998 TI - Acute effect of lidocaine on coronary blood flow and myocardial function. AB - The acute effects of lidocaine on coronary blood flow, hemodynamic parameters, and wall function were studied in 14 anesthetized pigs. Lidocaine was infused intravenously as a bolus (dosage range from 1.5 to 4.0 mg/kg). At ten to thirty seconds after infusion, coronary blood flow reached 154 +/- 38% (mean +/- SD) of the baseline resting flow (p less than 0.001). The double product, an estimate of myocardial oxygen demand, decreased from a baseline value of 9221 +/- 2174 to 8008 +/- 1923 mmHg beats/min (p less than 0.01). Sixty seconds postinfusion myocardial function decreased from baseline wall thickening of 46 +/- 25% to 41 +/- 17% (p = 0.04). An acute bolus of lidocaine appears to transiently increase coronary blood flow, by decreasing coronary vascular resistance, and also decrease myocardial function. Thus, an acute lidocaine bolus may favorably alter the myocardial oxygen supply/demand ratio. PMID- 2306000 TI - Hyperbaric oxygen therapy in chronic vascular wound management. AB - Many nonhealing tissues are hypoxic, with oxygen tensions frequently ranging from 5 to 15 mmHg. In such an environment, the normal wound healing sequence is disrupted or halted and phagocytic killing activity depressed. So the adjunctive use of hyperbaric oxygen (HBO), based on physiologic data and clinical observations, can provide the substrate necessary to initiate and sustain the healing process. During a twelve-month period, 20 patients with a nonhealing wound were referred to the hyperbaric center: chronic arterial insufficiency ulcers in 9 cases, diabetic wounds (foot lesions) in 11 cases. Adjunctive HBO therapy, initiated twice a day, consisted of pure oxygen, 2.5 ATA, 90 min. The average length of sessions was 46 (15-108). Complete healing was observed in 15 of 20 cases. The wound management can be helped with the transcutaneous oxygen measurements under hyperbaric oxygen. The distal TCPO2 at 2.5 ATA pure oxygen is a reliable test to predict final outcome (healing or no change), when these values were not different in normal air and in normobaric oxygen: (table; see text) In hyperbaric oxygen therapy, when the distal TCPO2 value was inferior to 100 mmHg, all patients showed either no improvement or aggravation, and when the value was higher than 100 mmHg, wound healing was achieved with all patients. PMID- 2305999 TI - Percutaneous angioplasty of totally occluded coronary vein bypass grafts: case histories. AB - Seven patients with totally occluded coronary artery bypass vein grafts underwent percutaneous transluminal angioplasty. All patients had either acute or recent occlusion of the graft itself. In 2 patients the proximal and in 3 the distal anastomosis were also narrowed. The vein graft was successfully dilated in all the patients. Six patients also received direct intragraft thrombolytic therapy during the procedure. Five uncomplicated patients improved clinically. One patient was studied routinely as part of a myocardial infarction-streptokinase protocol and had no symptoms. This patient had a no-reflow phenomenon. One patient did not receive intragraft thrombolytic therapy and the procedure was complicated by embolization with myocardial infarction and a cerebral embolus. In 2 patients, a routine angiogram was performed two to six months after graft dilatation and in both the grafts were patent. Another patient, initially successfully dilated, had recurrent angina and restenosis of the proximal anastomosis ten months after angioplasty; this was successfully redilated. Angioplasty of acutely or recently totally occluded coronary vein grafts is feasible and improves angina when present. Additional thrombolytic therapy prevents embolization. PMID- 2306001 TI - Streptokinase in the treatment of an acute cerebral embolus--a case report. AB - During cerebral angiographic examination of a sixty-five-year-old white male, an acute right hemiplegia resulting from embolic occlusion of the left middle cerebral artery developed. Intravenous streptokinase therapy was initiated within forty-five minutes of symptom onset and the hemiplegia cleared in approximately one hour with no evidence of intracranial hemorrhage. This observation underscores the applicability and potential benefits of immediate intravenous thrombolytic therapy for selected patients presenting with acute cerebral thrombosis or embolism. PMID- 2306002 TI - Restrictive cardiomyopathy following acute myocarditis--a case report. AB - A fifty-five-year-old man developed intractable heart failure four weeks after upper respiratory infection. His central venous pressure was as high as 300 mmH2O. Two-dimensional echocardiogram revealed no muscular hypertrophy of the ventricles, no pericardial thickness, and no pericardial effusion. On catheterization, hemodynamic data were compatible with restrictive cardiomyopathy. Transvenous endomyocardial biopsy of the left ventricle was performed. Histologic examination strongly suggested that cardiomyopathy developed after acute myocarditis. PMID- 2306003 TI - Acute anterior wall myocardial infarction secondary to blunt chest trauma--a case report. AB - Cardiac injuries following nonpenetrating chest trauma have been reported. These include cardiac arrhythmias, septal damage, valve damage, coronary fistula, coronary artery damage, ventricular aneurysm, cardiac rupture, and myocardial infarction. Myocardial infarction as a complication of chest trauma has been reported in very few cases. In this report the authors describe a patient who developed anterior wall myocardial infarction secondary to a blunt chest trauma. PMID- 2306005 TI - A pressor effect of noncardioselective beta-blockers in mildly hypertensive patients during acute hospitalization. AB - Pressor effects of noncardioselective beta-blockers have been demonstrated in situations of increased sympathetic activity; however, data are limited and the clinical significance of this finding is in doubt. The present study was performed to supply data about the effect of noncardioselective beta-blockers on the stress of acute hospitalization. Of 2,989 patients acutely admitted to a 50 bed unit of general internal medicine in a 647-bed teaching hospital, 234 had used beta-blockers without intrinsic sympathicomimetic activity (ISA) for at least six weeks because of mild hypertension; 199 were evaluable, 56 using nonselective, 143 using selective beta-blockers. The authors found a marked pressor effect of noncardioselective beta-blockers as compared with selective (mean arterial pressure 125 versus 102 mm Hg, p less than 0.001). In the patients who could continue their outpatient medication this effect could be attributed to an overall increase of total peripheral resistance and disappeared within five days of admission. In the patients admitted because of unstable angina pectoris (nonselective n = 15, selective n = 48) myocardial oxygen demand as estimated by the double product (systolic blood pressure heart rate) was significantly higher in the nonselective group (12.926 versus 9.581 mmHg.beats/min, p less than 0.01). The present study supports the need for more controlled data to determine the ultimate place of noncardioselective beta-blockers in situations of increased sympathetic activity. PMID- 2306004 TI - Effects of pentoxifylline and metabolite on red blood cell deformability as measured by ektacytometry. AB - The present investigation sought to evaluate the effects of pentoxifylline and its major hydroxyhexyl metabolite on red blood cell (RBC) deformability using the technique of ektacytometry. Red blood cells were harvested from normal volunteers (normal RBCs) and patients with sickle cell disease (abnormal RBCs) and incubated with varying concentrations of pentoxifylline and its major metabolite for varying time periods. The deformability of both treated and untreated RBCs from both patient groups was assessed by ektacytometric analysis. In contrast to the in vitro effects of pentoxifylline on whole-blood filterability, the present results demonstrated no effect of pentoxifylline or metabolite on RBC deformability at any concentration or incubation time period. Pentoxifylline does not enhance RBC deformability following acute in vitro incubation, and this suggests the need for further evaluation of the mechanism of action of this drug. PMID- 2306006 TI - Noninvasive and invasive diagnosis of a huge congenital aneurysm of the left atrium: a case report. AB - An intrapericardial aneurysm of the left atrium in a twenty-eight-year old asymptomatic woman is reported. The aneurysm was diagnosed by two-dimensional echocardiography and the specific intraaneurysmatic flow pattern was described by color blood flow imaging. To the authors' knowledge such a noninvasive diagnosis of a left atrial aneurysm has never been reported in the literature before. The diagnosis was confirmed by angiocardiography. The aneurysm was successfully resected. The patient was discharged without medication and continues to do well. PMID- 2306007 TI - Coronary angioplasty of bifurcational stenoses: a new approach utilizing a single guide, double-probe technique: case reports. AB - The authors describe a new approach to percutaneous transluminal coronary angioplasty (PTCA) of bifurcational lesions with a single-guide, "kissing balloon" technique, utilizing two probe dilatation systems, inserted simultaneously into the guiding catheter and across both diseased branches. The versatility of the probe dilatation system in complex angioplasty is portrayed, both for simultaneous or alternate balloon inflations, and the low-profile characteristics of the system are highlighted, which allow a double-probe introduction into a single guiding catheter, good visualization still being retained by guide injections. PMID- 2306008 TI - Homonymous quadrantic visual field defect resulting from vertebrobasilar insufficiency: report of a case. AB - A patient showing a congruous homonymous superior quadrantanopsia was found at autopsy to have infarction of the striate cortex. The lesion involved the inferior bank of the calcarine fissure almost entirely and approximately one fifth of the superior bank. Additionally, infarctions of the visual association cortex and the pontine tegmentum were found. No lesions in the corresponding temporal lobe were present. Two types of visual field defects have been described in association with occipital lobe lesions: a monocular temporal crescentic defect if the lesion is anterior and a congruous homonymous hemianopsia if it is posterior. This patient seems to represent a variant of the latter. The most prominent difference with respect to quadrantanopsias resulting from lesions of the optic radiation is the high degree of congruity, especially in the central portion of the field. Association with nonocclusive vascular events related to vertebrobasilar hypoperfusion rather than embolization is also more common. PMID- 2306009 TI - Traumatic coronary arteriovenous fistula communicating the left main coronary artery to pulmonary artery, associated with pulmonary valvular insufficiency and endocarditis: case report. AB - The authors present a case of a seventeen-year-old white male who suffered from a knife chest wound and secondarily developed a traumatic coronary arteriovenous fistula communicating the left main coronary artery to the pulmonary artery, associated with pulmonary valvular insufficiency and endocarditis. PMID- 2306010 TI - Atherosclerosic dissection of the cervical internal carotid artery--a case report. AB - Atherosclerosis as a cause of spontaneous dissection in the cervical internal carotid arteries has been described in only a few cases. The authors present a surgically and pathologically proven case of dissection on the base of atherosclerosis of the cervical internal carotid artery. A resection of the pathologic segment with arterial reconstruction by direct anastomosis with a venous patch graft was performed. The postoperative course was uneventful. PMID- 2306011 TI - Anomalous origin of the right coronary artery from the ascending aorta: case history. AB - A patient is described with an anomalous right coronary artery arising high above the left sinus of Valsalva. This patient is unique because the other 2 cases with such an anomalous origin of a right coronary artery had bicuspid aortic with such an anomalous origin of a right coronary artery had bicuspid aortic valves; this patient had a normal tricuspid aortic valve. PMID- 2306012 TI - Persistent neutropenia in a toddler. PMID- 2306013 TI - Bronchial reactivity and atopy in asthma discordant monozygotic twins. AB - Bronchial reactivity was studied in six asthma-discordant monozygotic twin pairs. In four pairs, atopy was confirmed in the asthmatic twin. It was not confirmed in any of the nonasthmatics. In five pairs, the asthmatic twin was markedly more reactive than the nonasthmatic partner. Bronchial reactivity correlated significantly with total IgE. The results indicate that hyperreactivity and atopy were acquired. PMID- 2306014 TI - Systemic allergic reaction to pine nuts. AB - This case report describes a systemic reaction due to ingestion of pine nuts, confirmed by an open, oral provocation test. Skin prick testing with the aqueous allergen revealed an immediate positive prick test, and histamine release from basophil leukocytes to the aqueous allergen was demonstrated. Radioallergosorbent test demonstrated specific IgE antibodies to pine nuts. In a review of medical literature, we found no reports of either oral provocation tests confirming a systemic reaction due to ingestion of pine nuts or demonstration of specific IgE antibodies. PMID- 2306015 TI - Apple juice challenge-pulmonary function test: a simple method to identify an acid-sensitive esophagus inducing bronchoconstriction: "the bronchoactive esophagus". PMID- 2306016 TI - Role of cockroaches in allergy to house dust in Calcutta, India. AB - Prick skin tests on 200 patients with a history of sensitivity to dust were done against house dust, cockroach, D. pteronyssinus, and D. farinae antigenic extracts. The frequency of positive reaction was 35% to cockroach, 59% to house dust, 84.7% to D. farinae, and 54% to D. pteronyssinus. Distinctively different prevalence of the three antigens, cockroach, house dust, and mites suggest that cockroach antigen is a specific antigen independent from house dust and mite antigens. PMID- 2306017 TI - Evaluation of new test (Phadiatop) for the screening of respiratory allergic disorders in children. AB - The present study investigated the sensitivity, specificity, and predictive value of a new in vitro test, the Phadiatop, which detects the presence in serum of specific IgE to a balanced mixture of the most frequent inhalant allergens. Ninety-eight children (63 males, 35 females) 2-12 years old (median age = 6), suffering from rhinitis and/or conjunctivitis and/or asthma were studied. Our data show that Phadiatop has an 87% sensitivity, a 100% specificity, a 92% efficiency, a 100% positive predictive value, and an 86% negative predictive value. These results indicate that Phadiatop is very effective in diagnosing atopy (no false positive). However, a negative Phadiatop does not exclude the diagnosis of atopy. PMID- 2306018 TI - Respiratory atopy in Rio de Janeiro. AB - An epidemiologic study was conducted in Rio de Janeiro, Brazil, evaluating 1,410 patients with asthma and/or rhinitis. Allergy skin testing was performed in 1,219 patients (intradermal and/or Multi-Test Lincoln Diagnostics techniques). Thirteen different allergens were tested: house dust, Dermatophagoides farinae, grasses, Alternaria tenuis, Hormodendrum hordei, Penicillium mix, Aspergillus fumigatus, dogs, cats, feathers, fleas, cockroaches, and household insects. The most frequent positive immediate allergy skin tests were house dust (74.08%) and mites (62.43%). PMID- 2306019 TI - Mold contamination of automobile air conditioner systems. AB - Eight cars belonging to patients who were found to have exacerbation of allergic rhinitis and bronchial asthma after turning on the air conditioner in their cars were examined. Mold concentrations inside the passenger compartment with the a/c turned off and at different climate control settings were lower than concentrations in the outside air. After turning on the air conditioner to "Max", cultures obtained at various intervals revealed that mold concentrations decreased significantly with time. Furthermore, placement of a filter at the portal of entry of outside air significantly reduced the mold concentration in the passenger compartment. PMID- 2306020 TI - Cutaneous responses to histamine, compound 48/80 and codeine in patients with hyperthyroidism. AB - The regulatory effects of various endocrine factors on allergic processes have been widely studied. The clinical importance of hyperthyroidism in asthma and in chronic urticaria has been demonstrated in several cases. These observations may be attributed to modulatory effects of thyroid hormones on mast cell releasability and/or on other target organs as blood vessels. To evaluate the effects of thyroid hormones on mast cell releasability and on the cutaneous vasculature, we analyzed the wheal and flare response to compound 48/80, to codeine, and to histamine in patients with hyperthyroidism and in a control group. No significant difference was found between the two groups. We could not demonstrate any in vivo effect of the thyrotoxic state on the cutaneous response to these substances. PMID- 2306021 TI - HIV and abrupt onset of atopy and anaphylaxis. PMID- 2306022 TI - [Peroxidase activity of urinary cell elements, leucocyturia and urinary tract infection]. AB - Peroxidase activity determination of urinary formed elements is proposed as a new leucocyturia detection method. Enzymatic activity is evidenced by hydrogen peroxide 0.54 mM in Trinder reagent. The reaction can be performed in filtrative microplate or in standard microplate. Results are formulated semi-quantitatively or using arbitrary units (UA/ml) respectively. Reproducibility of the peroxidase activity assay (n = 31, m = 754 UA/ml, CV = 6.8%) is higher than microscopic evaluation methods (direct microscopic examination: n = 31, m = 3, CV = 66%; standard sediment method: n = 31, m = 7, CV = 71%). Urine conservation is suitable during about 20 hours at 4 degrees C. In case of microscopic hematuria (less than 1.5 x 10(6) red blood cells/ml) only few interference was observed. On the other hand, macroscopic hematuria may be inhibitory for the enzymatic reaction. Peroxidase activity determination, microscopic leucocyte count and bacterial numeration were performed on 2,004, 1,589 and 1,709 urine samples, respectively. The low correlation between peroxidase activity and microscopic leucocyte count is discussed. This new enzymatic method contributes to detect urine samples with significant bacteriuria (greater than or equal to 10(5) UFC/ml): about 90 p. cent sensitivity and 95 p. cent negative predictive value. PMID- 2306023 TI - [Radioisotopic assay of total L-homocysteine in plasma and urine: application to serial determinations]. AB - The authors report here a simple radioenzymatic determination of total L homocysteine in plasma and urine. L-homocysteine-containing disulfides were reduced with dithioerythritol. L-homocysteine was then condensed by S-adenosyl L homocysteine hydrolase to 14C-adenosine to form S-14C adenosyl L-homocysteine that was separated from 14C-adenosine by paper descendant chromatography. The concentration of the total plasma L-homocysteine of 45 normal subjects was 8.04 +/- 0.26 (mean +/- SEM) mumol/l and total L-homocysteine concentration in urine was 0.59 +/- 0.06 mumol/mmol of creatinine (25 subjects). This method is as sensitive than the other methods described in the literature but more rapid and less expensive. PMID- 2306024 TI - [Influence of sampling conditions on the determination of the erythrocyte-plasma lithium ratio]. PMID- 2306025 TI - International Federation of Clinical Chemistry (IFCC). Scientific Division. Committee on pH, Blood Gases and Electrolytes. Guidelines for transcutaneous PO2 and PCO2 measurement. AB - This document provides guidelines in the terminology, methodology, and in the interpretation of data obtained from the use of skin (transcutaneous) P02 and PCO2 electrodes. The transcutaneous technique has found special application in newborn infants. The causes of analytical bias with respect to arterial blood gas values and imprecision obtained with transcutaneous P02 and PCO2 electrodes are reviewed. Electrode temperatures above 44 degrees C should not be used routinely, and, at a measuring temperature of 44 degrees C, the measuring site should be changed at least every 4 hours to avoid skin burning. PMID- 2306026 TI - International Federation of Clinical Chemistry. Education Division. Expert Panel on Quantities and Units. A protocol for the conversion of clinical laboratory data. PMID- 2306027 TI - [Metabolism of bile pigments in the intestine]. AB - This review discusses the knowledge on the transformation of bilirubin into urobilinoids before its elimination from the organism. The following aspects are presented: mechanism of bilirubin reduction by anaerobic intestinal bacteria, structure of the resulting urobilinoids, and enterohepatic circulation of the latter. Investigations on the reduction of bilirubin by intestinal bacteria in vitro are described, and the diagnostic value of urobilinoids determination is discussed. PMID- 2306028 TI - A new cable model formulation based on Green's theorem. AB - We describe an alternative formulation of the cable equation to model excitation in a cylinder of cardiac fiber. The formulation uses Green's theorem to develop equations for the extracellular and intracellular potential on either side of the excitable membrane, the dynamics of which are described by a Hodgkin-Huxley type model, without assuming that the radial current is zero. These equations are discretized to yield a system of linear equations which are solved at each instant in time. We found no qualitative differences between this approach and the standard cable model for parameters within accepted physiological limits. When the cable diameter is of the same order as the length constant the new formulation takes into account the intracellular potential change in the radial direction and gives an accurate expression of the conduction velocity. PMID- 2306029 TI - Optimum stimulus frequency for contracting the inspiratory muscles with chest surface electrodes to produce artificial respiration. AB - Electroventilation is the term used to describe the production of inspiration by applying a train of short-duration pulses to chest-surface electrodes. Studies were conducted in the dog to determine the optimum frequency to produce a smooth air flow in the trachea. It was found that a stimulus frequency of 25/sec or slightly higher meets this criterion. To illustrate that electroventilation can be carried out for a prolonged period using these parameters, electroventilation was applied continuously for 5 hours in a dog without a noticeable change in blood pressure. PMID- 2306030 TI - Mathematical models of the spatial distribution of retinal oxygen tension and consumption, including changes upon illumination. AB - To better understand oxygen utilization by the retina, a mathematical model of oxygen diffusion and consumption in the cat outer, avascular retina was developed by analyzing previously recorded profiles of oxygen tension (PO2) as a function of retinal depth. Simple diffusion modelling of the oxygen distribution through the outer retina is possible because the PO2 depends only on diffusion from the choroidal and retinal circulations and on consumption within the tissue. Several different models were evaluated in order to determine the best one from the standpoints of their ability to represent the data and to agree with physiological reality. For the steady state one-dimensional diffusion model adopted (the special three-layer diffusion model), oxygen consumption was constant through the middle layer and zero in the layers near the choroid and near the inner retina. On the average, the oxygen consuming layer, as found by nonlinear regression for each profile, extended from about 75% to 85% of the retinal depth from the vitreous. This is a narrow band through the mid-region of the photoreceptors. Oxygen consumption of the entire avascular retina, determined from fitting eight PO2 profiles measured in light-adapted retinas, averaged 2.7 ml O2(STP)/(100 g tissue.min), while the value determined from fitting thirty-two PO2 profiles measured in dark-adapted retinas averaged 4.4 ml O2(STP)/(100 g tissue.min). Consumption in the light was thus only 60% of that in the dark. This suggests that the outer retina is at greater risk of hypoxic injury in the dark than in the light, a finding of considerable clinical significance. PMID- 2306031 TI - Crosstalk resistant adaptive noise cancellation. AB - Presence of signal components in the reference input is detrimental to the performance of practical adaptive noise cancellation systems. Using a modeling approach, we analyse the performance of adaptive noise cancellation in the presence of signal cross talk. We demonstrate a crosstalk resistant adaptive noise cancellation method. After showing that the original signal cannot be recovered if the ability to prevent adaptation does not exist, we discuss the use of a weighted exact least squares lattice algorithm in the joint estimation form, where adaptation can be controlled. Using stimulated data, it is shown that signal can be estimated with good accuracy, even when there is significant signal crosstalk in the reference input. PMID- 2306032 TI - Studies of wall shear and mass transfer in a large scale model of neonatal high frequency jet ventilation. AB - The problem of endotracheal erosion associated with neonatal high-frequency jet ventilation (HFJV) is investigated through measurement of air velocity profiles in a scaled up model of the system. Fluid mechanical scaling principles are applied in order to construct a model within which velocity profiles are measured by hot-wire anemometry. The effects of two different jet geometries are investigated. Velocity gradients measured near the tracheal wall are used to measure the shear stresses caused by the jet flow on the wall. The Chilton Colburn analogy between the transport of momentum and mass is applied to investigate tracheal drying caused by the high shear flow. Shear forces are seen to be more than two times higher for jets located near the endotracheal tube wall than for those located axisymmetrically in the center of the tube. Since water vapor fluxes are dependent on these shears, they are also higher for the asymmetric case. Fluxes are shown to be greatly dependent on the temperature and relative humidity of the inspired gas. Water from the tracheal surface may be depleted within one second if inspired gases are inadequately heated and humidified. It is recommended that the design of neonatal HFJV devices include delivery of heated (near body temperature), humidified (as close to 100% humidity as possible) gases through an axisymmetric jet to best avoid the problem of endotracheal erosion. PMID- 2306033 TI - A theoretical description of arterial pressure-flow relationships with verification in the isolated hindlimb of the dog. AB - We developed and tested a new two-compartment serial model of the arterial vasculature which unifies the capacitance (downstream arterial compliance) and waterfall (constant downstream pressure load) theories of blood flow through the arteries. In this model, blood drains from an upstream compliance through a resistance into a downstream compliance which empties into the veins through a downstream resistance which terminates in a constant pressure load. Using transient arterial pressure data obtained from an isolated canine hindlimb preparation, we tested this model, using a stop-flow technique. Numerical parameter estimation techniques were used to estimate the physiologic parameters of the model. The downstream compliance was found to be more than ten times larger than the upstream compliance and the constant pressure load was significantly above venous pressures but decreased in response to vasodilation. Our results support the applicability of both the capacitance and waterfall theories. PMID- 2306034 TI - Home health care finds new ways of caring: skilled RNs meet patient needs as agencies flourish. PMID- 2306035 TI - Visiting Nurses Association nurses--experts and more. PMID- 2306036 TI - RN makes house calls to sick kids. Interview by Patricia McCarty. PMID- 2306037 TI - National Commission on Nursing Implementation Project/Advertising Council campaign challenges resistant stereotypes. PMID- 2306038 TI - ANA reports new health care law. PMID- 2306039 TI - How to become certified in 1990. PMID- 2306040 TI - State nursing associations share commitment to collective bargaining. PMID- 2306041 TI - State nursing associations, unions compete for members. PMID- 2306043 TI - RNs work to keep America healthy. PMID- 2306042 TI - When trouble strikes, Red Cross RNs are there. PMID- 2306044 TI - Center helps get your career on track. PMID- 2306045 TI - AIDS poses confidentiality risk. PMID- 2306046 TI - Home health care comes of age. PMID- 2306047 TI - RNs tell what's new in home health care. PMID- 2306048 TI - As I see it. Blacks in nursing: an update. PMID- 2306049 TI - As I see it. Drug problem touches us all. PMID- 2306050 TI - Nurse builds center for adult day care. Interview by Patricia McCarty. PMID- 2306051 TI - Surgical management of perforated Crohn's disease. AB - The records of 102 patients operated on by one of the authors for Crohn's disease during the past 15 years were reviewed. Twenty-seven patients with confined (abscess present) or free perforation were evaluated. The average age was 31 years and the mean duration of disease was four years. Only two of the 27 patients had had previous surgery. All patients presented with a combination of pain, weight loss, and diarrhea. Twenty-three patients were afebrile, 17 had abdominal tenderness, and 6 had an abdominal mass. The average serum albumin was 3.7, the average hematocrit was 35 per cent and the average WBC was 13,000. Radiologic tests were abnormal in 23 of the 27 patients. All patients had been on medical treatment for Crohn's disease, and 19 of 27 were on high-dose steroids at the time of surgery. Ten of the 27 had a bowel prep before surgery and all had preoperative and postoperative antibiotics. All patients were surgically managed by resection and primary anastomosis without proximal diversion or delayed reconstruction. Drains were used in one third of the patients. Intraoperative cultures revealed gram-negative rods with Escherichia coli, enterococcus, and Enterobacter the most common. One enterocutaneous fistula, two superficial wound infections, and one death were recorded. Based on these results, the authors believe that an aggressive one-stage surgical approach for these complicated problems can be recommended. The low morbidity and mortality justifies this approach that results in considerable improvement in lost work time, length of hospital stay, number of readmissions, and significant cost control. PMID- 2306052 TI - Prospective clinicopathophysiologic follow-up study of asymptomatic neck bruit. AB - Three hundred asymptomatic carotid bruits (ACB) were followed prospectively, clinically, and by duplex ultrasound with Gee/ocular plethysmography (OPG) for a period ranging from one to 72 months (mean, 32 months). All patients underwent baseline duplex/OPG, which was repeated every six months until the endpoint, transient ischemic attack (TIA) or cerebrovascular accident (CVA). One hundred seven had arteriograms. Five classes were identified: class I (normal): 96/300 (32%), 79 of these were followed and one had TIA (1/79, 1.3%); class II (less than 50% stenosis): 118/300 (39%), 105 of these were followed, three had TIA, and one had CVA (4/105, 3.8%); class III (50-60% stenosis): 25/300 (8%), 21 were followed, one had TIA (1/21, 4.7%); class IV (more than 60% stenosis with negative OPG): 39/300 (13%), 34 were followed, three had TIA, and one had CVA (4/34, 11.7%); and class V (more than 60% stenosis with positive OPG): 22/300 (7%), 18 were followed, three had TIA, and one had CVA (4/18, 22.2%). Data was analyzed using chi-square with Yates correction. In conclusion, in ACB 32 per cent had no carotid stenosis and 39 per cent had minimal disease with minimal risk of TIA or stroke. Patients with the most severe stenoses (classes IV and V) had a statistically significantly higher likelihood of TIA or CVA occurring during the follow-up period. This last group (class V) would be ideal for prophylactic carotid endarterectomy. PMID- 2306053 TI - Regional perfusion for the treatment of subungual melanoma. AB - Thirty-one patients with subungual melanoma representing 2.6 per cent of all patients with limb melanoma were treated by isolated regional perfusion. Acral lentiginous melanoma prevalent on subungual and volar skin was the most common histologic type. The subungual lesions primarily occurred on the lower limbs (61%) and great toe (48%). At diagnosis, most patients had advanced disease; 53 per cent of stage I patients had lesions with level IV invasion or greater. The median thickness of the primary lesion was 2.35 mm. All patients were treated by isolated regional perfusion and amputation of the involved digit, as well as regional lymph-node dissection where clinically indicated. The mean survival rate for all stages at five years was 35 per cent. Patients with stage I disease had the best survival rates, 61 per cent at five years and 54 per cent at ten years; however, patients with advanced disease, stage III (M.D. Anderson classification), had only a 17 per cent survival rate at five years and 8 per cent at 10 years. Women had slightly better survival rates than men, and patients with upper-limb lesions had the better prognosis. PMID- 2306054 TI - The management of penetrating pelvic trauma. AB - Eighty-nine patients with penetrating pelvic trauma were treated during a three year period. Sixty-three of 72 patients who had mandatory exploration had findings at operation. The negative laparotomy rate was higher for patients with posterior penetrations (40%). Diagnostic peritoneal lavage, sigmoidoscopy, and intravenous pyelography were useful adjunctive tests to confirm the lack of need for exploration in patients with negative physical findings. This protocol of tests was particularly useful for patients with posterior sites of injury. Patients with injury to multiple organ systems had a higher rate of infectious complications (48%) than those with single system injury (11% complication rate). Primary repair of colon, urologic and vascular injuries was safe even in patients with injury to multiple organ systems. PMID- 2306055 TI - Current management of choledocholithiasis. AB - Choledocholithiasis may be managed by surgical extraction of stones or endoscopic papillotomy with extraction of stones. To evaluate these methods of management, the charts of all patients with choledocholithiasis admitted to Crawford Long Hospital of Emory University between April 1, 1983, and April 30, 1988, were reviewed. One hundred patients were identified; 42 were treated by common bile duct exploration (CBDE) and 58 had endoscopic papillotomy with extraction of stones (EP) as their initial treatment. The two groups were similar in regards to age, but the CBDE group had more comorbid conditions (average 2.5/patient in CBDE vs 1.8/patient in EP) and a higher incidence of acute cholecystitis and/or cholangitis (74% of CBDE patients; 24% of EP patients). Successful extraction of all stones occurred in 79 per cent of CBDE patients and 90 per cent of EP patients. Of those patients with retained stones following CBDE, all were later extracted by EP. Of patients having EP as their initial procedure, 24 per cent required repeat endoscopic procedures for extraction of residual stones and only six patients (10.4%) required CBDE for retained stones. Morbidity was lower (10% vs 23%) and hospital stay shorter (3.6 days vs 10.4 days) in the EP than CBDE patients; thus, the two groups are not completely comparable. Mortality was similar in the two groups (1.7% EP, 2.3% CBDE). PMID- 2306056 TI - Breast biopsy. Changing patterns during a five-year period. AB - The current emphasis on early detection of breast carcinoma prompted an analysis of all breast biopsies performed at an urban teaching hospital between January 1, 1983, and December 31, 1987. There were 1,342 biopsies during this interval in 933 patients with an overall mean age of 45.3 years. Malignancy was diagnosed in 197 patients (14.7%) with a mean age of 57.5 years, while the remaining patients with a benign diagnosis had a mean age of 43.2 years. There were 178 nonpalpable lesions (13.3%) and 22 malignancies were detected in this group (12.4%). Most (91%) of the nonpalpable malignancies were "early" (in situ and stage I), while 71 per cent of the palpable malignancies were "advanced" (stages II and III). Although the yearly number of biopsies remained constant, upward trends were demonstrated in the number of nonpalpable lesions biopsied, the proportion of malignancies detected among all biopsies, and in the yield of proliferative benign forms of breast disease, specifically those with atypia. These trends correlated with a sixfold increase in the yearly number of mammograms performed over the same time interval. These results suggest that a commitment to an expanded use of mammography and to an aggressive approach to breast biopsy can increase the detection of both early forms of breast carcinoma and those benign breast lesions that are known pathologic risk determinants for breast carcinoma. Such a commitment may influence the future survival of this population. PMID- 2306057 TI - Penetrating pancreatic injuries. Analysis of 103 consecutive cases. AB - The optimal management of penetrating pancreatic injuries continues to be a matter of debate and controversy. The present study analyzes 103 consecutive patients with these wounds treated at a level I Trauma Center in a 14-year period (1975-1988). Twenty-seven patients died within 48 hours from extensive associated trauma (Abdominal Trauma Index [ATI] 46.7). The majority of the remaining 76 patients were treated by debridement and drainage. Nineteen patients with grade III injuries had distal pancreatectomy. Six patients with extensive combined pancreatoduodenal injuries had pancreatoduodenectomy. Pancreatoenteric anastomoses or duodenal diversion procedures rarely were used. Pancreatic complications included major fistulas in four patients (5%) and pancreatic abscess in nine patients (11%). Only one of the fistulas required subsequent fistulojejunostomy. Intra-abdominal abscesses occurred in 18 patients (23.6%), mostly in patients with associated colon injury (P less than 0.001). It is concluded that a conservative approach to penetrating pancreatic injuries yields optimal results and that associated colon injury is an important predeterminant for abscess formation. PMID- 2306058 TI - Is diagnostic peritoneal lavage for blunt trauma obsolete? AB - Diagnostic peritoneal lavage was 97 percent accurate, with a 2 percent false positive rate and a 1 percent false negative rate in this series of 414 patients. The ease, safety, and accuracy of diagnostic peritoneal lavage justify its continued use in evaluating these patients. Recent studies show computerized tomography (CT) can be highly accurate in detecting intra-abdominal injuries after blunt trauma. We reviewed our experience with diagnostic peritoneal lavage (DPL) to evaluate whether the accuracy, safety, speed, and cost justified its continued use. Four hundred fifteen DPLs were performed on 414 patients from February 1, 1983, through December 31, 1987. All DPLs were done by the open technique. The lavage was considered grossly positive if 10 cc gross blood were aspirated. If there were greater than 100,000 red blood cells (RBC)/mm3, greater than 500 white blood cells (WBC)/mm3, elevated amylase or bilirubin, or bacteria or vegetable fibers the lavage was microscopically positive. There were no cases with elevated bilirubin, amylase, or presence of bacteria. All four cases with "rare vegetable fibers" were false positive. Six DPLs were for penetrating trauma to the lower chest or back. There were 291 negative lavages, including five false negatives (1%), and 124 positive DPLs, including seven false positives (2%), resulting in a crude accuracy of 97 percent. Three of the five false negative lavages had a ruptured diaphragm as the only intra-abdominal injury. There was one minor complication. DPL was usually performed in the trauma resuscitation room during the secondary survey. At our institution, the total fees for DPL are +185 less than the fees for CT. DPL is accurate, rapid, safe, and avoids the disruption of patient care that results in the radiology suite. DPL remains our procedure of choice for evaluating blunt abdominal trauma in the adult. PMID- 2306059 TI - What physicians should know about the nursing shortage. PMID- 2306060 TI - The carpal tunnel syndrome: diagnostic utility of the history and physical examination findings. AB - STUDY OBJECTIVE: To assess the value of a history and physical examination findings in diagnosing the carpal tunnel syndrome, and to determine whether constellations of clinical findings identify patients at high or low risk for the carpal tunnel syndrome. DESIGN: Comparison of diagnostic tests with neurophysiologic testing. SETTING: Patients with upper extremity complaints of diverse causes referred to a neurophysiology laboratory for diagnostic studies. METHODS: Before nerve conduction testing, a history, demographic and physical examination data, and a hand pain diagram were obtained from each patient. Diagrams were categorized as indicating the classic carpal tunnel syndrome, or as probable, possible, or unlikely to indicate the carpal tunnel syndrome. Associations between clinical data and nerve conduction results were examined in univariate and multivariate analyses. RESULTS: Of 110 patients in the study, 44 (40%) had the carpal tunnel syndrome. Individually, the best predictors were hand pain diagram rating (positive predictive value, 0.59; 95% CI, 0.48 to 0.68) and Tinel sign (positive predictive value, 0.55, CI, 0.45 to 0.65). The combination of a positive Tinel sign and a probable or classic diagram rating had a positive predictive value of 0.71; CI, 0.53 to 0.85. Other findings from physical examination and the history were less useful. Just 9% of patients under 40 years of age with possible or unlikely diagram ratings had the carpal tunnel syndrome. CONCLUSIONS: With the exceptions of age, Tinel sign, and hand pain diagram rating, findings from the physical examination and the history had limited diagnostic utility. Patients under 40 years of age with possible or unlikely diagram ratings were at low risk for the carpal tunnel syndrome. This finding, which should be confirmed in an independent population, suggests that subsets of patients may be managed without nerve conduction studies. PMID- 2306061 TI - Bolus or intravenous infusion of ranitidine: effects on gastric pH and acid secretion. A comparison of relative efficacy and cost. AB - STUDY OBJECTIVE: To compare the effects of intravenous bolus injection of ranitidine, continuous intravenous infusion of ranitidine, and placebo on gastric pH, acid secretion, and plasma ranitidine concentration during a 24-hour period, and to determine by survey the use, delivery methods, and costs of histamine H2 receptor antagonists in intensive care units. DESIGN: Double-blind, Latin-square randomized, prospective measurement of the gastric pH, acid output, and plasma ranitidine concentration over 24 hours in response to six treatment regimens in 12 patients with inactive duodenal ulcer. Eight regional hospitals were surveyed to obtain information on the use of histamine H2-receptor antagonists. INTERVENTIONS: Gastric acid secretion, pH, and plasma ranitidine were monitored for 24 hours on six separate days in response to placebo, intravenous bolus injection of ranitidine (50 mg every 8 hours and 75 mg every 12 hours), and continuous intravenous infusion of ranitidine (75, 150, and 300 mg every 24 hours). MEASUREMENTS AND MAIN RESULTS: Intravenous infusions were significantly more effective than bolus injections. After bolus injections, hourly gastric pH values fluctuated widely, from 7.6 to 1.6, whereas during continuous infusion of 150 mg and 300 mg, hourly pH values were 3.8 or greater. The gastric pH was greater than 4.0 in 75% +/- 5% and 83% +/- 6% of determinations done during continuous intravenous infusion of 150 mg and 300 mg, respectively. Fluctuations in the plasma ranitidine concentration corresponded with changes in gastric pH and acid secretion. Histamine H2-receptor antagonists were prescribed for about 75% of patients in intensive care units and were most commonly administered by bolus rather than infusion (5:1); the cost was approximately +40 per day less by infusion. CONCLUSIONS: On the basis of both efficacy and cost, intermittent bolus injections should be discontinued and replaced by continuous intravenous infusion in hospitalized patients requiring treatment with histamine H2-receptor antagonists. If ranitidine is used, either 150 mg or 300 mg administered as a 24 hour continuous infusion is most effective. PMID- 2306062 TI - The natural history of carotid bruits in elderly persons. AB - STUDY OBJECTIVE: To determine the relative risk for cerebrovascular events in elderly patients with carotid bruits. DESIGN: Population-based prospective study. SETTING: Community-based home for the aged. PATIENTS: All patients were residents of a home for the aged and were at least 75 years old in 1985. MEASUREMENTS AND MAIN RESULTS: Two hundred and forty-one residents were examined for carotid bruits and signs of previous stroke. The mean age of the residents was 86 years. Twelve percent of residents had asymptomatic carotid bruits. The prevalence of asymptomatic carotid bruits was 8% in residents who were 75 to 84 years of age, 10% in residents who were 85 to 94 years of age, and 13% in residents who were at least 95 years old. Interval cerebrovascular events and cause of death were ascertained from chart review, and recorded events in survivors were confirmed by a repeat examination. The 3-year cumulative incidence of cerebrovascular events in asymptomatic residents with carotid bruits was 10%, compared with 9% in residents without carotid bruits, yielding a relative risk of 1.1 (95% CI, 0.45 to 2.7). In 60% of surviving residents, baseline carotid bruits were no longer present at the time of follow-up examination. The disappearance of these bruits was not associated with the occurrence of interval cerebrovascular events. CONCLUSIONS: The prevalence of asymptomatic carotid bruits increases with advanced age. Carotid bruits do not greatly increase the risk for subsequent stroke in elderly patients. Carotid bruits may often disappear without clinical sequelae. PMID- 2306063 TI - Development of diffuse fasciitis with eosinophilia during L-tryptophan treatment: demonstration of elevated type I collagen gene expression in affected tissues. A clinicopathologic study of four patients. AB - We describe the cases of four women who developed a scleroderma-like syndrome during L-tryptophan treatment for insomnia or tinnitus. The illness was characterized by swelling of the extremities, skin rash, myalgia, and elevation of the peripheral blood eosinophil count, followed by rapidly progressive cutaneous and subcutaneous induration. The histopathologic examination of affected skin showed thickening of the fascia, deep dermal fibrosis, and accumulation of mononuclear cells and abundant eosinophils. The expression of the type I procollagen gene was examined by in-situ hybridizations of affected skin with a human sequence-specific complementary DNA (cDNA). Increased hybridization signals were detected in the deep dermis and fascia, indicating enhanced expression of the collagen gene. The temporal association of L-tryptophan use and the development of a scleroderma-like illness in these four patients suggests a causal relation between L-tryptophan or its metabolites and the stimulation of fibroblast collagen gene expression that results in dermal and fascial fibrosis. PMID- 2306064 TI - Driving-impaired patients leaving the emergency department. The problem of inadequate instructions. AB - STUDY OBJECTIVE: We evaluated the frequency with which blood alcohol concentrations were obtained in emergency department patients with presumed alcohol impairment, whether physicians counseled impaired patients not to drive, and whether safe transportation was available. DESIGN: Retrospective chart review and search of the North Carolina Driver History file. SETTING: Emergency departments of a university and affiliated Veterans Affairs Medical Center (VAMC). PATIENTS: Consecutive adult patients at the university (n = 1554) and VAMC (n = 1461) emergency departments. Patients with presumed alcohol-induced impairment (university, 75; VAMC, 88) who did not require hospital admission were identified. Presumed alcohol-induced impairment was defined by any of the following: nurse or physician note specifying the patient was intoxicated; indication in the medical record that the patient had alcohol on their breath; claim by the patient of alcohol use the day of evaluation; or measurement of blood alcohol concentration. MEASUREMENTS AND MAIN RESULTS: Blood alcohol concentrations were measured in 80% of presumed alcohol-impaired university patients (median blood alcohol concentration, 45 mmol/L) and 68% of VAMC patients (median blood alcohol concentration, 58 mmol/L). Driving skills deteriorate with blood alcohol concentrations of 11 mmol/L or greater; however, 63% of university and 88% of VAMC patients with measured blood alcohol concentrations of 11 mmol/L or greater were still impaired when discharged. Only 3.5% of university and 8.7% of VAMC patients impaired at discharge were advised not to drive, whereas 31% of university and 20% of VAMC patients impaired at discharge were supervised by a responsible person. The prevalence of previous driving-while-impaired convictions was high (university, 34%; VAMC, 58%). CONCLUSIONS: Presumed alcohol-impaired patients seen in emergency departments frequently have blood alcohol concentrations measured. Despite documented evidence of driving impairment there is little evidence that such patients are counseled not to drive or that safe transportation home is available. PMID- 2306065 TI - Primary care internal medicine: a challenging career choice for the 1990s. AB - A career in primary care internal medicine can be challenging and rewarding, yet during the last decade fewer medical students have selected training in internal medicine. We wish to inform medical students, their advisors, and other physicians about the field of primary care internal medicine. We define the discipline, compare it with traditional internal medicine and with family practice, and describe features of strong primary care internal medicine training programs. We discuss common misconceptions and concerns about training programs and the career and give examples of career paths chosen by graduates of primary care programs. We encourage students to consider the option of primary care internal medicine when making career decisions and provide faculty advisors unfamiliar with primary care internal medicine training programs with a reference resource. PMID- 2306066 TI - Fulminant hepatitis as a consequence of reactivation of hepatitis B virus infection after discontinuation of low-dose methotrexate therapy. PMID- 2306067 TI - Carotid endarterectomy. PMID- 2306068 TI - Crohn disease and intravenous immunoglobulin G. PMID- 2306069 TI - Firesetting by patients with the acquired immunodeficiency syndrome (AIDS) PMID- 2306070 TI - Bacterial cultures for cystitis. PMID- 2306071 TI - Hypothyroidism and thyrotropin-secreting pituitary microadenomectomy. PMID- 2306072 TI - 'Immediately available'--two words that require many more to explain them. PMID- 2306073 TI - Delegation and assignment clarification. PMID- 2306074 TI - Nurses disagree with 'President's Message'. PMID- 2306075 TI - Quality assurance. A system for surgical services. PMID- 2306076 TI - OR directors' survey. A report from the Special Committee on Critical Issues. PMID- 2306077 TI - Ethylene oxide. An occupational health hazard for hospital workers. AB - Hospitals present a variety of infectious, chemical, and physical hazards at levels comparable to the hazards encountered in many industries. Our society has acquired the scientific and technological capability to identify and abate hazardous chemical exposures. Thus, the knowledge needed to resolve the problem effectively is available, and now, it only needs to be applied. The knowledge related to EtO can be summarized into three major points. Exposure to EtO can result in cancer, reproductive abnormalities including genetic damage, and neurological disease. Prevention of exposure to EtO requires sensitive and informed hospital administrators, adequate aeration and ventilation, personal and area monitoring, a written compliance program, and employee information and education. Perioperative nurses must protect their patients and the perioperative team from potential hazards of EtO. PMID- 2306078 TI - What pleases OR nurses? Results of an OR nurse retention survey. AB - Although it seems like the dissatisfiers outnumber reasons nurses enjoy OR nursing, significant strides are being made in some areas of the country, particularly in the area of compensation, better prepared managers, self governing, and involvement in decision making. It is vital that OR managers prepare themselves in the areas of business and human resource management so that they can be effective leaders in the coming decade. PMID- 2306079 TI - Project Alpha. Designing courses that recruit and retain OR nurses. AB - Those who participated in developing and teaching the courses gained many new skills including writing objectives and test questions, public speaking, and expertise in the topics they taught. Another benefit was the sense of pride and accomplishment in developing and presenting a quality postgraduate program. This was reinforced by student evaluations as the course progressed. In addition, they were paid by the college as salaried faculty members. The clinical preceptors benefited through the relationships they developed with their students. They were given the opportunity to exhibit their clinical skills and experienced pride and satisfaction as their novice colleagues grew. The students reaped the benefit of instruction from perioperative nurses who were enthusiastic and committed to the practice of perioperative nursing. They also received information from experienced nurses who were functioning in the OR on a daily basis. The small class size was another benefit because it allowed ample time for questions and individual instruction. Project Alpha has been an ongoing focus of the AORN of Alameda County for approximately 10 years. The chapter began with a three-day observational experience for sophomore nursing students and moved on to include a perioperative elective and management preceptorship for upper-division nursing students. Most recently, the chapter has supported the postgraduate perioperative course described in this article. The nurses completing this postgraduate program enter perioperative practice with a strong base of knowledge and sense of professionalism. PMID- 2306080 TI - OR nursing in developing countries. Present conditions, future hopes. PMID- 2306081 TI - Preoperative teaching. A study of nurses' perceptions. PMID- 2306082 TI - Proposed recommended practices. Use of the pneumatic tourniquet. AORN Technical Practices Coordinating Committee. PMID- 2306083 TI - Ethical dilemmas in perioperative research. PMID- 2306084 TI - When a hospital closes--one nurse's perspective. PMID- 2306085 TI - Detection of coliform bacteria in water by polymerase chain reaction and gene probes. AB - Polymerase chain reaction (PCR) amplification and gene probe detection of regions of two genes, lacZ and lamB, were tested for their abilities to detect coliform bacteria. Amplification of a segment of the coding region of Escherichia coli lacZ by using a PCR primer annealing temperature of 50 degrees C detected E. coli and other coliform bacteria (including Shigella spp.) but not Salmonella spp. and noncoliform bacteria. Amplification of a region of E. coli lamB by using a primer annealing temperature of 50 degrees C selectively detected E. coli and Salmonella and Shigella spp. PCR amplification and radiolabeled gene probes detected as little as 1 to 10 fg of genomic E. coli DNA and as a few as 1 to 5 viable E. coli cells in 100 ml of water. PCR amplification of lacZ and lamB provides a basis for a method to detect indicators of fecal contamination of water, and amplification of lamB in particular permits detection of E. coli and enteric pathogens (Salmonella and Shigella spp.) with the necessary specificity and sensitivity for monitoring the bacteriological quality of water so as to ensure the safety of water supplies. PMID- 2306086 TI - Aerobic and anaerobic growth of rifampin-resistant denitrifying bacteria in soil. AB - The growth and survival of several rifampin-resistant isolates of denitrifying bacteria were examined under anaerobic (denitrifying) and aerobic conditions. Two isolates added to nonsterile Bruno soil at densities of between 10(4) and 10(6) CFU g dry soil-1 exhibited an initial period of growth followed by a gradual decline in numbers. After 28 days, both isolates maintained viable populations of between 10(4) and 10(5) CFU g dry soil-1 under both denitrifying and aerobic conditions. One of the isolates consistently grew better under denitrifying conditions, and the other isolate consistently grew better under aerobic conditions. The relative pattern of denitrifying versus aerobic growth for each organism was not affected by the addition of glucose. The growth yields of the two isolates varied with soil type, but the relative pattern of denitrifying versus aerobic growth was consistent in three soils with greatly different properties. Five of nine isolates introduced into Bruno soil at low population densities (approximately 10(5) CFU g dry soil-1) exhibited better growth after 2 days under denitrifying conditions. It was not possible to predict the prevalence of the denitrifying or aerobic mode of growth in nonsterile soil from the growth characteristics of the isolates in pure cultures or sterile soil. PMID- 2306087 TI - Transfer of the toxin protein genes of Bacillus sphaericus into Bacillus thuringiensis subsp. israelensis and their expression. AB - The genes encoding the toxic determinants of Bacillus sphaericus have been expressed in a nontoxic and a toxic strain of Bacillus thuringiensis subsp. israelensis. In both cases, the B. sphaericus toxin proteins were produced at a high level during sporulation of B. thuringiensis and accumulated as crystalline structures. B. thuringiensis transformants expressing B. sphaericus and B. thuringiensis subsp. israelensis toxins did not show a significant enhancement of toxicity against Aedes aegypti, Anopheles stephensi, and Culex pipiens larvae. PMID- 2306088 TI - Enumeration and biomass estimation of planktonic bacteria and viruses by transmission electron microscopy. AB - Bacteria and virus particles were harvested from water samples by ultracentrifugation directly onto Formvar-coated electron microscopy grids and counted in a transmission electron microscope. With this technique, we have counted and sized bacteria and viruses in marine water samples and during laboratory incubations. By X-ray microanalysis, we could determine the elemental composition and dry-matter content of individual bacteria. The dry weight/volume ratio for the bacteria was 600 fg of dry weight microns-3. The potassium content of the bacteria was normal compared with previous estimates from other bacterial assemblages; thus, this harvesting procedure did not disrupt the bacterial cells. Virus particles were, by an order of magnitude, more abundant than bacteria in marine coastal waters. During the first 5 to 7 days of incubation, the total number of viruses increased exponentially at a rate of 0.4 day-1 and thereafter declined. The high proliferation rate suggests that viral parasitism may affect mortality of bacteria in aquatic environments. PMID- 2306089 TI - Omasal ciliated protozoa in cattle, bison, and sheep. AB - Omasal contents were collected from slaughtered cattle (n = 54), bison (n = 15), and sheep (n = 40) to determine numbers and generic distribution of ciliated protozoa. Total protozoan numbers were significantly lower in omasal contents than in ruminal contents of all three species, but the percent composition of all protozoan genera was similar between omasal and ruminal populations. The highest numbers of omasal protozoa found were 7.61 X 10(5)/g in cattle, 7.01 X 10(5)/g in bison, and 1.29 X 10(6)/g in sheep. Omasal dry matter was significantly higher than ruminal dry matter in all species and ranged up to 51.5% in cattle fed high concentrate diets. The omasal pH was similar to the ruminal pH in all species. The number of omasal laminae averaged 149, 145, and 74 for cattle, bison, and sheep, respectively. Although protozoan concentrations in omasal contents were approximately 80% lower than those in ruminal contents, the omasum harbored relatively high numbers of ciliated protozoa. The resident omasal protozoa are extremely difficult to remove, particularly in cattle, and apparently are responsible for reinoculating transiently defaunated rumens. PMID- 2306090 TI - Ammonia-oxidizing bacteria in a chloraminated distribution system: seasonal occurrence, distribution and disinfection resistance. AB - Nitrification in chloraminated drinking water can have a number of adverse effects on water quality, including a loss of total chlorine and ammonia-N and an increase in the concentration of heterotrophic plate count bacteria and nitrite. To understand how nitrification develops, a study was conducted to examine the factors that influence the occurrence of ammonia-oxidizing bacteria (AOB) in a chloraminated distribution system. Samples were collected over an 18-month period from a raw-water source, a conventional treatment plant effluent, and two covered, finished-water reservoirs that previously experienced nitrification episodes. Sediment and biofilm samples were collected from the interior wall surfaces of two finished-water pipelines and one of the covered reservoirs. The AOB were enumerated by a most-probable-number technique, and isolates were isolated and identified. The resistance of naturally occurring AOB to chloramines and free chlorine was also examined. The results of the monitoring program indicated that the levels of AOB, identified as members of the genus Nitrosomonas, were seasonally dependent in both source and finished waters, with the highest levels observed in the warm summer months. The concentrations of AOB in the two reservoirs, both of which have floating covers made of synthetic rubber (Hypalon; E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.), had most probable numbers that ranged from less than 0.2 to greater than 300/ml and correlated significantly with temperature and levels of heterotrophic plate count bacteria. No AOB were detected in the chloraminated reservoirs when the water temperature was below 16 to 18 degrees C. The study indicated that nitrifiers occur throughout the chloraminated distribution system. Higher concentrations of AOB were found in the reservoir and pipe sediment materials than in the pipe biofilm samples. The AOB were approximately 13 times more resistant to monochloramine than to free chlorine. After 33 min of exposure to 1.0 mg of monochloramine per liter (pH 8.2, 23 degrees C), 99% of an AOB culture was inactivated. The amounts of this disinfectant that are currently used (1.5 mg/liter at a 3:1 ratio of chlorine to ammonia-N) may be inadequate to control the growth of these organisms in the distribution system. PMID- 2306091 TI - Absence of trichothecenes in toxigenic isolates of Fusarium moniliforme. AB - Thirty-four isolates of Fusarium moniliforme were obtained from cereal grains collected in various parts of the world. The isolates were grown on rice and tested as a diet for toxicity to rats. Of these isolates, 53% caused death, 12% caused congestion and hemorrhage of the stomach and intestine as well as hematuria, 21% caused diarrhea, 38% caused weight loss, and 9% were nontoxic. The cultures were tested to T-2, HT-2, neosolaniol, acetyl-T-2, T-2-tetraol, iso-T-2, diacetoxyscirpenol, monoacetoxyscirpenol, deoxynivalenol, nivalenol, fusarenone X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, zearalenone, moniliformin, fusarochromanone, fusarin-C, and wortmannin; all were negative. In addition, F. moniliforme NRRL A25820 was grown on corn and banana fruit as solid substrates as well as on a defined liquid medium; none of the above toxins were found. When F. moniliforme NRRL A25820 was incorporated into a rat diet, no toxicity was noted. Twenty-eight additional isolates of F. moniliforme, isolated from feed associated with equine leukoencephalomalacia, were grown on cracked corn for 2 weeks. The cultures were negative when tested for deoxynivalenol, 15-acetyldeoxynivalenol, diacetoxyscirpenol, monoacetoxyscirpenol, nivalenol, and fusarenone X. Seventy five percent of the isolates were toxic to ducklings, indicating the presence of a toxin other than trichothecenes. Our results support the conclusion that F. moniliforme does not produce trichothecenes. PMID- 2306092 TI - Degradation of pentachlorophenol by a Flavobacterium species grown in continuous culture under various nutrient limitations. AB - A Flavobacterium sp. was grown in continuous culture limited for growth with ammonium, phosphate, sulfate, glucose, glucose + pentachlorophenol (PCP) (0.065 h -1), or PCP. Cells ere harvested, washed, and suspended to 3 x 10(7) cells ml ( 1) in shake flasks containing a complete mineral salts medium without added carbon or supplemented with 50 mg of PCP ml(-1) or 50 mg of PCP ml(-1) + 100 mg of glucose ml(-1). The PCP concentration and the viable cell density were determined periodically. Cells that were grown under phosphate, glucose, or glucose + PCP limitation were more sensitive to PCP and took longer to degrade 50 mg of PCP ml(-1) than did cells that very were grown under ammonium, sulfate, or PCP limitation. Glucose stimulated viability and PCP degradation in all cases except when the cells were grown under carbon limitation with glucose and PCP added together as the carbon source. These results indicate that there is a relationship between nutrient limitation, phenotypic variation, and the sensitivity to and degradation of PCP by this organism. PMID- 2306093 TI - Production of staphylococcal enterotoxins C1 and C2 and thermonuclease throughout the growth cycle. AB - Synthesis of enterotoxins C1 and C2 and thermonuclease throughout the growth cycle was investigated with Staphylococcus aureus type strains FRI137 and FRI361 and S. aureus isolates M5 (C1) and L2 (C2) of animal origin. Both enterotoxins were produced during the exponential growth phase or at the beginning of the stationary phase. The minimal incubation time (7 to 12 h) and the lowest population (10(7) to 2 x 10(9) CFU/ml) associated with detectable enterotoxin (1 to 6.5 ng/ml) were related to the total amount of toxin produced after 24 h. Thermonuclease was detected in all samples whenever enterotoxins were detected. Furthermore, strain FRI137 produced thermonuclease earlier and at lower cell populations than it did enterotoxin C1. Patterns of enterotoxin and thermonuclease synthesis did not correlate. The concentration of toxins increased throughout the growth cycle, while the concentration of thermonuclease remained constant during the last hours of the growth cycle. PMID- 2306094 TI - Detection of the osmoregulator betaine in methanogens. AB - Trimethyl glycine (glycine betaine) was detected by 13C nuclear magnetic resonance spectroscopy at high intracellular concentrations in several methanogens (Methanogenium cariaci, "Methanogenium anulus" AN9, Methanohalophilus zhilinae, Methanohalophilus mahii, and Methanococcus voltae) grown on marine media containing yeast extract. 13C labeling studies with Methanogenium cariaci suggested that the betaine which accumulated inside the cells was not synthesized de novo but was transported in from the medium. Proof of such a transport system was provided by growing Methanogenium cariaci on yeast-free medium supplemented with betaine. Under these conditions, betaine was the dominant osmoregulator. PMID- 2306095 TI - Equilibrium temperature in a clump of bacteria heated in fluid. AB - A theoretical model was developed and used to estimate quantitatively the "worst case", i.e., the longest, time to reach equilibrium temperature in the center of a clump of bacteria heated in fluid. For clumps with 10 to 10(6) cells heated in vapor, such as dry and moist air, and liquid fluids such as purees and juices, predictions show that temperature equilibrium will occur with sterilization temperatures up to 130 degrees C in under 0.02 s. Model development highlighted that the controlling influence on time for heating up the clump is the surface convection thermal resistance and that the internal conduction resistance of the clump mass is negligible by comparison. The time for a clump to reach equilibrium sterilization temperature was therefore decreased with relative turbulence (velocity) of the heating fluid, such as occurs in many process operations. These results confirm widely held suppositions that the heat-up time of bacteria in vapor or liquid is not significant with usual sterilization times. PMID- 2306096 TI - Biotransformation of substituted benzoates to the corresponding cis-diols by an engineered strain of Pseudomonas oleovorans producing the TOL plasmid-specified enzyme toluate-1,2-dioxygenase. AB - The conversion of substituted benzoates into 1,2-cis-dihydroxycyclohexa-3,5-diene carboxylic acids (cis-diols) was effected by using Escherichia coli and Pseudomonas recombinants carrying the xylXYZ genes originating from the Pseudomonas putida mt-2 TOL plasmid, thus producing toluate-1,2-dioxygenase. Pseudomonas oleovorans GPo12 recombinants readily produced meta- and para substituted cis-diols, but were limited in their oxidation of ortho-substituted substrates. PMID- 2306097 TI - Studies on the subsite specificity of the rat brain puromycin-sensitive aminopeptidase. AB - The specificity of the puromycin-sensitive aminopeptidase from rat brain was examined. Using L-alanyl-beta-naphthylamide as substrate Vmax of the reaction was shown to be pH independent over the range of 5.5-9.0, while Km exhibited a pKa of 7.7. This latter value corresponds to the pKa of the amino group of the substrate. Using X-Ala and X-Leu to examine the specificity of the P1 site it was found that Arg and Lys exhibit the highest affinity, followed by Met, Val, Leu, Trp, and Phe, which bind congruent to 5- to 20-fold less well. Although Km varied more than 20-fold within this series, Vmax showed considerably less variation. Significantly weaker binding was observed with a P1 Gly, Ala, Ser, or Pro with no binding detectable with a P1 Glu. The presence of a P'1 Leu compared to P'1 Ala results in an approximate 10-fold decrease in Km with little change in Vmax. The effect of varying P'1 residues was examined with the series Leu-X. In this case basic and hydrophobic amino acids, with the exception of Val, all exhibit nearly the same Km. The binding of Arg-Arg and Lys-Lys showed the same Km as obtained for Arg-Leu or Lys-Leu, respectively. When Leu-Ser-Phe was compared to Leu-Ser the P'2 residue led to a 100-fold decrease in Km and slightly less than a 5-fold increase in Vmax. In contrast the addition of a P'2 Met to Leu-Trp results in only a 3-fold decrease in Km and a 3-fold increase in Vmax. The results indicate a preference for a basic or hydrophobic residue in the P1 and P'1 sites and indicate subsite-subsite interactions which primarily affect binding. PMID- 2306098 TI - Kinetic study of nucleophile specificity in dipeptide synthesis catalyzed by clostridiopeptidase B. AB - The kinetic parameters of Clostridiopeptidase B-catalyzed aminolysis of carbobenzoxyarginyl methyl ester leading to the formation of various dipeptides are investigated. The deacylation rates of the acylenzyme were evaluated by direct product analysis using high-performance liquid chromatography on a reversed-phase column. On the basis of the partitioning ratio and the first-order and second-order rate constants for the deacylation step, large differences in the nucleophile reactivities, which appear to be related to a S'1-P'1 interaction, were observed. The order of specificity was established as Leu much greater than Ser greater than Phe greater than Val greater than Ala = Gly much greater than Pro with second-order rate constants ranging from 578,614 M-1 s-1 for leucinamide to 5132 M-1 s-1 in the case of prolinamide. All of the amino acid amides had a nucleophilic strength at least 10 times higher than that of water during the deacylation step. The data reported here represent the first experimental evidence for the existence of a S'1 site engaged in the recognition of the amino acid side chain residue for this enzyme. The recognition site showed an increase in the affinity along with an increase in the hydrophobicity of the amino acid amide side chains. PMID- 2306099 TI - Evidence for the presence of distinct flavin-containing monooxygenases in human tissues. AB - Catalytic activities and substrate specificity of flavin-containing monooxygenase were examined in human tissues. During incubation with imipramine, human hepatic microsomes efficiently carried out cytochrome P450-dependent reactions but not the formation of N-oxide, while in kidney imipramine N-oxide was the only metabolite formed during in vitro incubation. The production of imipramine N oxide was essentially due to flavin-containing monooxygenase as shown by thermal inactivation. In contrast, thiobenzamide and dimethylaniline were actively transformed by both human liver and kidney flavin-containing monooxygenase. Neither the modification of pH nor the solubilization of microsomal membranes increased imipramine N-oxidation in human liver. Kinetic analysis indicated a poor affinity (about 7 mM) of human liver microsomes for imipramine versus 0.3 mM in kidney. Immunological studies were undertaken to support enzymatic data. Antibodies raised against rat liver flavin-monooxygenase reacted strongly with human kidney microsomes but extremely weakly with liver microsomes. The relative amount of immunochemically determined protein correlated well with imipramine N oxidation activity. A dose-dependent inhibition of imipramine N-oxidation by anti flavin-monooxygenase antibodies was observed in human kidney, as well as in rat kidney and liver. Taken together, the results can be interpreted by the possible existence in human tissues of distinct flavin-containing monooxygenases exhibiting a partial overlapping substrate specificity. The protein involved in imipramine N-oxidation is missing from human liver but actively carries out the reaction in kidney, while another protein catalyzes the oxidation of thiobenzamide and dimethylaniline in both tissues. PMID- 2306100 TI - Characterization of the effects of propranolol on the physical state of platelet membrane. AB - The direct membrane effect of propranolol was studied in vitro on washed platelet preparations. Propranolol has been reported to inhibit platelet aggregation by mechanisms unrelated to its beta-blocking activity. In the present study, the drug was found to enhance 1-anilino-8-naphthalene sulfonate binding to platelet membrane by increasing the number of binding sites. Steady-state anisotropy was studied by labeling the platelets with the hydrophobic fluorescent probe 1,6 diphenyl-1,3,5-hexatriene. Propranolol was observed to decrease the equivalent microviscosity of the membrane. When the infinitely slow decaying component of fluorescence anisotropy (r infinity), which is proportional to the square of lipid order parameter, was calculated from the anisotropy data, a decrease in these parameters was also indicated. A higher fusion activation energy for viscosity in the propranolol-treated platelets reflected a lesser degree of order of the hydrocarbon chains in the lipid bilayer. PMID- 2306102 TI - Phytoalexin synthesis in soybean: purification and characterization of NADPH:2' hydroxydaidzein oxidoreductase from elicitor-challenged soybean cell cultures. AB - An NADPH:2'-hydroxydaidzein oxidoreductase (HDR) from elicitor-challenged soybean cell cultures was purified to apparent homogeneity by a five-step procedure. The purification procedure included affinity adsorption on Blue Sepharose and elution of the enzyme with NADP+. It was shown by gel filtration and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis that HDR consists of only one polypeptide, which has a Mr about 34,700. The pH optimum of the reaction was 7.0. Apparent Michaelis constants determined for 2'-hydroxydaidzein, 2' hydroxyformononetin, and NADPH were, respectively, 50, 60, and 56 microM. A low conversion of 2'-hydroxygenistein to the corresponding isoflavanone was also observed but isoflavones lacking a 2'-hydroxyl group and various other flavonoids did not serve as substrates. Enzymatically derived 2'-hydroxydihydrodaidzein gave a positive CD spectrum at 328 nm, which shows its 3R stereochemistry. Antibodies against HDR were raised in rats. PMID- 2306101 TI - C4 acid decarboxylation and photosynthesis in bundle sheath cells of NAD-malic enzyme-type C4 plants: mechanism and the role of malate and orthophosphate. AB - The mechanism and possible regulation of C4 acid decarboxylation in NAD-malic enzyme-type C4 plants was studied using isolated bundle sheath cells and mitochondria from Panicum miliaceum. Rates of C4 acid-dependent photosynthetic O2 evolution equalled those observed with saturating NaHCO3; the rates ranged from 3 to 5 mumol min-1 (mg chlorophyll)-1. C4 acid-dependent O2 evolution required the addition of aspartate and 2-oxoglutarate (as a source of oxaloacetate) and also malate and orthophosphate. C4 acid decarboxylation by both isolated cells and mitochondria, measured as pyruvate production, also required all four of these components. The scheme previously proposed to account for aspartate decarboxylation in NAD-malic enzyme-type C4 plants does not envisage a role for externally derived malate. However, the mandatory requirement for malate (with orthophosphate), together with the observation that C4 acid decarboxylation is blocked by an inhibitor of the mitochondrial dicarboxylate transporter, suggests that a net flux of malate from outside the mitochondria is required to sustain this process. Arsenate was found to substitute for orthophosphate favoring a role for orthophosphate in malate transport rather than a metabolic one. The results are discussed in terms of likely mitochondrial metabolite transport mechanisms and regulation of the C4 acid decarboxylation process. PMID- 2306103 TI - Characterization of cell-associated proteoglycans synthesized by embryonic neural retinal cells. AB - To begin to understand the properties of the neuronal heparan sulfate proteoglycan (HSPG) that interacts with the neural cell adhesion molecule (NCAM), we have analyzed proteoglycans synthesized by dissociated embryonic retinal cells in culture. Because NCAM plays an integral role in cell-cell interactions, we have focused on cell-associated HSPGs. Proteoglycans were isolated from embryonic Day 10 retinal cell cultures labeled with 35SO4 and separated into fractions that either flowed through or were retained on phenyl-Sepharose. Molecules binding phenyl-Sepharose have been proposed to be capable of insertion into the plasma membrane, and thus may be involved in binding to NCAM. Proteoglycans binding to phenyl-Sepharose had an estimated molecular mass of 400-500 kDa, and contained 60% HSPG and 40% chondroitin sulfate proteoglycan (CSPG). The putative membrane associated HSPGs, with an average molecular weight of 360 kDa, were shown to contain heparan sulfate chains of 40 and 20 kDa, and multiple core proteins with the major core protein having a molecular weight of approximately 130 kDa. The membrane-associated CSPGs also exhibited multiple core proteins, with sizes ranging from 120 to 220 kDa. These data suggest that multiple membrane-associated HSPGs and CSPGs are synthesized by embryonic neural retina cells, which may explain the diversity in function of this class of proteoglycans. PMID- 2306104 TI - Characterization of reactions catalyzed by manganese peroxidase from Phanerochaete chrysosporium. AB - Manganese peroxidase (MnP) is one of two extracellular peroxidases believed to be involved in lignin biodegradation by the white-rot basidiomycete Phanerochaete chrysosporium. The enzyme oxidizes Mn(II) to Mn(III), which accumulates in the presence of Mn(III) stabilizing ligands. The Mn(III) complex in turn can oxidize a variety of organic substrates. The stoichiometry of Mn(III) complex formed per hydrogen peroxide consumed approaches 2:1 as enzyme concentration increases at a fixed concentration of peroxide or as peroxide concentration decreases at a fixed enzyme concentration. Reduced stoichiometry below 2:1 is shown to be due to Mn(III) complex decomposition by hydrogen peroxide. Reaction of Mn(III) with peroxide is catalyzed by Cu(II), which explains an apparent inhibition of MnP by Cu(II). The net decomposition of hydrogen peroxide to form molecular oxygen also appears to be the only observable reaction in buffers that do not serve as Mn(III) stabilizing ligands. The nonproductive decomposition of both Mn(III) and peroxide is an important finding with implications for proposed in vitro uses of the enzyme and for its role in lignin degradation. Steady-state kinetics of Mn(III) tartrate and Mn(III) malate formation by the enzyme are also described in this paper, with results largely corroborating earlier findings by others. Based on a comparison of pH effects on the kinetics of enzymatic Mn(III) tartrate and Mn(III) malate formation, it appears that pH effects are not due to ionizations of the Mn(III) complexing ligand. PMID- 2306105 TI - Effects of 1,25-dihydroxyvitamin D3 and its analogs on butyrate-induced differentiation of HT-29 human colonic carcinoma cells and on the reversal of the differentiated phenotype. AB - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) greatly enhances sodium butyrate (NaB) induced enterocyte differentiation of HT-29 human colonic carcinoma cells while 1,25-(OH)2D3 alone induces growth restriction without associated differentiation. In the present study, the efficacies of various analogs of 1,25-(OH)2D3 to enhance NaB-induced HT-29 differentiation and to prolong the reversal of the differentiated phenotype under NaB-free growth conditions were subsequently examined. Extent of HT-29 differentiation was assessed by measurement of alkaline phosphatase (AP) activity, appearance of mucin-producing cells, changes in morphological characteristics, and expression of differentiation-associated cytokeratin proteins. Among active analogs of 1,25-(OH)2D3, 26,26,26,27,27,27 hexafluoro-1,25-(OH)2D3 (F6-1,25-(OH)2D3), 24,24-difluoro-24-homo-1,25-(OH)2D3, and 26,27-dimethyl-1,25-(OH)2D3 were 100-, 10-, and 5-fold, respectively, more effective than 1,25-(OH)2D3 in enhancing NaB-induced mucin production. Combined use of NaB and F6-1,25-(OH)2D3 (10(-9) M) also induced HT-29 cells to form highly differentiated goblet-like enterocytes, and increased both cellular AP enzymatic activity and tissue-type cytokeratin content. This differentiated state was qualitatively more advanced than that achieved by a combination of NaB and 10(-7) M 1,25-(OH)2D3. NaB-mediated HT-29 differentiation (in short-term inductions) was found to be reversible following a return to NaB-free medium. HT-29 cells differentiated by combined use of NaB and 1,25-(OH)2D3 or its analogs exhibited a significant prolonged reversal time relative to cells differentiated with NaB alone. The most prominent effect was achieved using cells differentiated with NaB and 10(-9) M F6-1,25-(OH)2D3 which exhibited a 7-fold prolonged reversal time over colonocytes differentiated by NaB alone. Our data suggest that a combined use of NaB and 1,25-(OH)2D3 or its derivatives may provide a convenient in vitro model system to probe molecular events associated with steroid-target tissue interactions in a differentiating cell system as commonly occurs in vivo. Such an analysis might lend itself to design of a rational combination differentiation based therapy for the clinical management of colon cancer. PMID- 2306106 TI - The dopamine transporter and cytochrome P45OIID1 (debrisoquine 4-hydroxylase) in brain: resolution and identification of two distinct [3H]GBR-12935 binding proteins. AB - Two [3H]GBR-12935 binding proteins, identified as the dopamine transporter and cytochrome P45OIID1, were solubilized in digitonin from canine striatal membranes, and were resolved following wheat germ agglutinin (WGA)-lectin column chromatography. Protein adsorbed to and specifically eluted from WGA-lectin with N-acetylglucosamine displayed saturable, high affinity (KD approximately 3 nM), and sodium-dependent binding of [3H]GBR-12935, which was inhibited in a concentration-dependent and stereoselective manner by dopamine uptake blockers and substrates with a pharmacological profile indicative of the dopamine uptake site. Protein not adsorbed to WGA-lectin also bound [3H]-GBR-12935 with high affinity (approximately 7 nM), in a sodium-independent manner, and was insensitive to classical dopamine uptake blockers and substrates such as mazindol or dopamine, corresponding to the so-called "piperazine acceptor" site seen in native membranes. [3H]GBR-12935 binding to this latter protein was, however, inhibited by various compounds with a pharmacological profile indicative of a form of cytochrome P450 designated P45OIID1 (debrisoquine/sparteine monooxygenase) with the following rank order of inhibitory potency: GBR-12909 greater than budipine greater than alpha-lobeline greater than quinidine greater than alpha flupenthixol greater than SKF-525A greater than sparteine greater than quinine. Ki values obtained for inhibition of [3H]-GBR-12935 binding to neuronal WGA passthrough fractions by these drugs correlate well with their respective Ki values for liver P45OIID1 activity. Western blotting and immunoprecipitation analysis with rabbit anti-rat P45OIID1 antibody also supported the identity of the mazindol-insensitive [3H]GBR-12935 binding site (or piperazine acceptor site) as P45OIID1. Furthermore, a [3H]GBR-12935 binding protein with pharmacological and immunological characteristics similar to those of P45OIID1 was solubilized from both bovine and human liver membranes, and GBR-12909 was found to be a potent competitive inhibitor (Ki approximately 100 nM) of sparteine monooxygenase activity in human liver microsomes. These data clearly indicate that [3H]GBR 12935 and its analogs display similar affinities for both the dopamine transporter and neuronal P45OIID1, and that this radioligand may be a useful probe of P45OIID1 activity in brain and liver. The exact molecular and functional association (if any) between these two distinct binding protein populations remains to be established; however, it is tempting to speculate that P45OIID1 is involved in the catabolism and processing of neurotransmitters subsequent to their reuptake into target cells. PMID- 2306107 TI - Precursor-product relationship of larger to smaller molecular forms of the BAL 31 nuclease from Alteromonas espejiana: preferential removal of duplex exonuclease relative to endonuclease activity by proteolysis. AB - Two molecularly and kinetically distinct major species of the extracellular nuclease BAL 31 from Alteromonas espejiana, previously characterized as the "fast" (F) and "slow" (S) BAL 31 nucleases, have been evidenced to derive from proteolysis starting from a still larger (approximately 120 kDa) precursor nuclease. The expected protease activity in the culture fluid has been confirmed and is strongly dependent on the cell growth phase. The disappearance of the largest nuclease species with the concomitant sequential appearance of first the F and then the S species has been demonstrated for nuclease obtained from culture supernatants as a function of cell growth phase. Nuclease from periplasmic extracts displayed very little of the F and S nucleases. Treatment of purified F nuclease with Pronase or subtilisin readily converted it to species with only a few percent of the native exonuclease activity against duplex DNA but retaining much of the initial activity against single-stranded DNA. Electrophoresis in nuclease-detecting gels demonstrated a parallel conversion of the larger species to one indistinguishable in molecular weight from the S species. The observed loss of exonuclease activity could correspond to the conversion of the F to the S nuclease. However, treatment of S nuclease with subtilisin resulted in a drastic reduction of exonuclease activity of this enzyme on duplex DNA with retention of most of the activity against single-stranded and nicked circular duplex DNA substrates. Evidence of internal proteolysis of the S nuclease could be seen after electrophoresis in denaturing gels but only after the denaturation buffer was adjusted to 6 M in urea. The preferential removal of the exonuclease activity may enhance the usefulness of the BAL 31 nuclease in such applications as heteroduplex mapping. PMID- 2306108 TI - Characterization of three cytochrome P450s purified from renal microsomes of untreated male rats and comparison with human renal cytochrome P450. AB - Three renal cytochrome P450s (P450 K-2, K-4, and K-5) were purified from renal microsomes of untreated male rats. Also, the human renal cytochrome P450 (P450 HK) was partially purified from renal microsomes and its properties were compared with those of the rat renal cytochrome P450s. The molecular weight of P450 K-2, K 4, and K-5 was 52,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The absolute spectrum of the oxidized forms indicated that they had the low-spin state of heme, and the CO-reduced spectral maxima of P450 K-2, K 4, and K-5 were at 449, 451, and 452 nm, respectively. NH2-terminal sequence analysis of P450 K-2, K-4, and K-5 showed that these forms were different from hepatic cytochrome P450s purified previously. P450 K-2, K-4, and K-5 catalyzed the O-dealkylation of 7-ethoxycoumarin but were not efficient in the hydroxylation of testosterone. Aminopyrine was metabolized by P450 K-2 and K-4 but not by P450 K-5. Lauric acid was metabolized efficiently by all of these forms in the presence of cytochrome b5. The regiospecificity of these forms toward lauric acid was different. P450 K-2 hydroxylated lauric acid only at the (omega-1)-position, not at the omega-position. P450 K-4 and K-5 hydroxylated lauric acid at both the omega- and (omega-1)-positions. The ratios of omega/(omega-1)-hydroxylation activity of P450 K-4 and K-5 were 2.5 and 7.8, respectively. Human P450 HK was purified 220-fold and its specific content was 2.0 nmol/mg of protein. The Soret maxima of P450 HK were at 418 nm for the oxidized form, 416 nm for the reduced form, and 450 nm for the CO-reduced form. P450 HK catalyzed the O-dealkylation of 7-ethoxycoumarin but was not efficient in aminopyrine N-demethylation or testosterone hydroxylation. P450 HK had high lauric acid omega- and (omega-1)-hydroxylation activities in the presence of cytochrome b5, especially omega-hydroxylation. These properties resembled those of P450 K-5 most closely. Anti-P450 K-5 antibody cross-reacted with P450 HK as well as P450 K-5 and only one band was stained on immunostained Western blotting for partially purified P450 HK. The molecular weight of P450 HK was 52,000 on Western blotting. PMID- 2306109 TI - Reexamination of the 1H NMR assignments and solution conformations of L-carnitine and O-acetyl-L-carnitine using C-2 stereospecifically labeled monodeuterated isomers. AB - The two C-2 monodeuterated isomers of L-carnitine were synthesized by enzymatic hydration of crotonobetaine in D2O and by enzymatic proton exchange of L-[2 2H2]carnitine in H2O. These reactions, catalyzed by an induced Escherichia coli carnitine hydrolyase proceed stereospecifically. The two isomers of L-[2 2H]carnitine were examined by 1H NMR at 500 MHz, which allowed us to independently monitor the pD dependence and coupling constants of the H-2 protons. The results obtained indicate that there is little effect of the carboxyl charge on the conformational state(s) of L-carnitine about the C-2/C-3 bond. The NMR data obtained in this study do not support previous solution studies of the pH-dependent conformational changes for DL-carnitine nor the proposed conformation of O-acetyl-DL-carnitine in the crystalline state. PMID- 2306110 TI - Allene oxide cyclase: a new enzyme in plant lipid metabolism. AB - The mechanism of the biosynthesis of 12-oxo-10,15(Z)-phytodienoic acid (12-oxo PDA) from 13(S)-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid in preparations of corn (Zea mays L.) was studied. In the initial reaction the hydroperoxide was converted into an unstable allene oxide, 12,13(S)-epoxy 9(Z),11,15(Z)-octadecatrienoic acid, by action of a particle-bound hydroperoxide dehydrase. A new enzyme, allene oxide cyclase, catalyzed subsequent cyclization of allene oxide into 9(S),13(S)-12-oxo-PDA. In addition, because of its chemical instability, the allene oxide underwent competing nonenzymatic reactions such as hydrolysis into alpha- and gamma-ketol derivatives as well as spontaneous cyclization into racemic 12-oxo-PDA. (+/-)-cis-12,13-Epoxy-9(Z)-octadecenoic acid and (+/-)-cis-12,13-epoxy-9(Z),15(Z)-octadecadienoic acid, in which the epoxy group was located in the same position as in the allene oxide substrate, served as potent inhibitors of corn allene oxide cyclase. On the other hand, the isomeric (+/-)-cis-9,10-epoxy-12(Z)-octadecenoic acid had little inhibitory effect. Allene oxide cyclase was present in the soluble fraction of corn homogenate and had a molecular weight of about 45,000 as judged by gel filtration. The enzyme activity was detected in several plant tissues, the highest levels being observed in potato tubers and in leaves of spinach and white cabbage. PMID- 2306111 TI - Purification and properties of xylanase from the thermophilic fungus, Humicola lanuginosa (Griffon and Maublanc) Bunce. AB - An extracellular xylanase was purified to homogeneity from the culture filtrate of the thermophilic fungus, Humicola lanuginosa (Griffon and Maublanc) Bunce and its properties were studied. A fourfold purification and a yield of 8% were achieved. The molecular weight of the protein was found to be 22,500 based on electrophoretic mobility and 29,000 by gel filtration behavior. The protein is rich in acidic amino acids, glycine and tyrosine, and poor in sulfur-containing amino acids. The kinetic properties of the enzyme are similar to those of other fungal xylanases. The enzyme shows high affinity toward larchwood xylan (Km = 0.91 mg/ml) and hydrolyzes only xylan. The enzyme becomes inactivated when stored for more than 2 months at -20 degrees C in the dry state. Such an inactivation has not been reported so far for any xylanase. Using chromatographic techniques, one species of protein differing from the native protein in charge but enzymatically active was isolated in low yields. However, a large molecular weight species of the protein devoid of enzyme activity was isolated in substantial quantities and further characterized. Based on ultracentrifugation and gel electrophoretic studies, it was concluded that this species may be an aggregate of the native protein and that such an aggregation might be taking place on storage in the dry state at -20 degrees C, leading to loss in activity. PMID- 2306113 TI - Physical and chemical scavenging of singlet molecular oxygen by tocopherols. AB - Singlet molecular oxygen (1O2) arising from the thermal decomposition of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate was used to assess the effectiveness of alpha-, beta-, gamma-, and delta-tocopherol in the physical quenching as well as the chemical reaction of 1O2. The relative physical quenching efficiencies of the tocopherol homologs were found to decrease in the order of alpha greater than or equal to beta greater than gamma greater than delta-tocopherol. The ability of physical quenching depends on a free hydroxyl group in position 6 of the chromane ring. Chemical reactivity of the tocopherol homologs with 1O2 was low, accounting for 0.1-1.5% of physical quenching with beta-tocopherol showing particularly low reactivity, resulting in the sequence alpha greater than gamma greater than delta greater than beta-tocopherol. Tocopheryl quinones were products of all tocopherol homologs, and in addition a quinone epoxide was a major product from gamma-tocopherol. This quinone epoxide was not cleaved by rat liver microsomal epoxide hydrolase; however, it reacted further with 1O2. It is concluded that methylation in position 5 of the chromane ring enhances physical quenching of 1O2, whereas chemical reactivity is favored by a methylated position 7. In view of the fact that beta-tocopherol is as effective as alpha-tocopherol in physical quenching of 1O2 but shows very low chemical reactivity, this tocopherol homolog might be particularly suitable for biological conditions in which an accumulation of oxidation products might weaken the antioxidant defense. PMID- 2306112 TI - Partial purification and characterization of an acetylcarnitine hydrolase from bovine epididymal spermatozoa. AB - We previously reported that intact epididymal spermatozoa from bulls and hamsters oxidize [1-14C]acetyl-L-carnitine to 14CO2 at about the same rate as they oxidize [1-14C]acetate. In addition, we showed that acetylcarnitine is hydrolyzed by a hydrolase present in the plasma membrane and that the carnitine moiety does not enter the cell. Here we report the partial purification of the acetylcarnitine hydrolase from bovine spermatozoa and describe some of its properties. The detergent-extracted enzyme was purified by FPLC using an anion-exchange Mono-Q column. The hydrolase activity eluted from the column with the application of 0.22 to 0.30 M NaCl and was separated from acetylcholinesterase activity, which eluted with 0.35 to 0.40 M NaCl. Specific inhibitors of acetylcholinesterase had little effect on acetylcarnitine hydrolase but p-hydroxymercuriphenylsulfonate was a potent inhibitor of the hydrolase. Kinetic studies of the hydrolase yielded a K'm of 6-10 mM for acetylcarnitine and a V'max of 0.16 nmol min-1 mg protein-1. Similar studies with the acetylcholinesterase yielded a K'm for acetylcholine of about 300 microM and a V'max of 165 nmol min-1 mg protein-1. Acetylcarnitine was a poor substrate for the acetylcholinesterase. Several acyl-L-carnitines were tested as substrates for the hydrolase and the preferred substrate was acetylcarnitine. The role of acetylcarnitine hydrolase in the metabolism of acetylcarnitine by epididymal spermatozoa is discussed. PMID- 2306114 TI - Photoionization used as a tool for the study of biomembranes: fate of tetramethylbenzidine photocation in purple membrane. AB - Photoionization of hydrophobic probes has been developed in micelles or synthetic vesicles. Studies of the yields, compartmentation, and lifetimes of the photo produced charged species have gathered reliable information on the interfacial and structural properties of these assemblies. Such an approach has never been applied to biological membranes. The present system is tetramethylbenzidine as the probe in native or modified (deionized and/or bleached) purple membrane from halobacteria. The data on photocation formation yields (phi ion) and lifetimes (tau 1/2) allow two main conclusions to be made: (1) tetramethylbenzidine, as the cation, is buried in the membrane core, and (2) its incorporation does not alter the biological activity of the protein. In this biological membrane the photocation lifetime and yield present the same trend of variation with the surface potential but to less of an extent than in model membranes. Bleaching of purple membrane completely modifies the photoionization process and the photocation decay. In addition, these experiments reveal a tight correlation between membrane structure and probe photoionization. Further evidence for structural modification of purple membrane, either by deionization or by bleaching is pointed out. PMID- 2306115 TI - Synthesis and study of (Z)-3-chlorophosphoenolpyruvate. AB - (Z)-3-Chlorophosphoenolpyruvate has been synthesized by the reaction of 3,3 dichloropyruvic acid with trimethylphosphite, followed by deesterification. This compound is a competitive inhibitor of pyruvate kinase and phosphoenolpyruvate carboxylase. Pyruvate kinase is not inactivated upon prolonged incubation with the compound, but phosphoenolpyruvate carboxylase is slowly inactivated (t1/2 = 5 h). The compound is a substrate for both enzymes, being acted upon by pyruvate kinase approximately 0.1% as rapidly as phosphoenolpyruvate itself. In the case of phosphoenolpyruvate carboxylase, the compound is converted into a 3:1 mixture of chloropyruvate and chlorooxalacetate, at an overall rate that is about 25% the carboxylation rate for phosphoenolpyruvate. PMID- 2306116 TI - Inhibition of glutathione reductase by oncomodulin. AB - Evidence for a specific interaction between oncomodulin and glutathione reductase is presented. Glutathione reductase (EC 1.6.4.2) isolated from either the bovine intestinal mucosa or the rat liver was bound in a Ca2(+)-dependent manner to oncomodulin which was covalently attached to Sepharose. In addition, glutathione reductase was able to catalyze the reduction of the disulfide-linked dimer of oncomodulin. The interaction of these proteins could also be indirectly demonstrated by monitoring glutathione reductase activity since oncomodulin was shown to inhibit the enzyme in a dose-dependent manner with an apparent IC50 of approximately 5 microM. The kinetic analysis of the oncomodulin-dependent effects on glutathione reductase activity indicates that oncomodulin interacts at a site other than the active site as the oncomodulin-induced inhibition was of the noncompetitive type. The in vivo inhibition of glutathione reductase appears to be an oncomodulin-specific effect as closely related members of the troponin C superfamily such as rabbit (pI 5.5) or carp (pI 4.25) parvalbumins, as well as calmodulin, failed to affect the activity of this enzyme. The present in vitro study indicating that oncomodulin can regulate the activity of glutathione reductase could be very significant with respect to the elucidation of a physiological role for oncomodulin. PMID- 2306117 TI - Inhibition of ischemia and reflow-induced liver injury by an SOD derivative that circulates bound to albumin. AB - Ischemia followed by reflow often results in tissue injury. Although reactive oxygens seem to play an important role in the pathogenesis of postischemic reflow induced tissue injury, the mechanism and an efficient way to inhibit oxidative injury are not known. We studied the mechanism by which hepatic transport function was inhibited by a transient occlusion followed by reflow of the portal vein and hepatic artery by using a superoxide dismutase (SOD) derivative (SM-SOD) which circulates bound to albumin with a half-life of 6 h. Occlusion of the hepatic vessels for 20 min followed by reflow for 60 min significantly inhibited transhepatic transport of cholephilic ligands, such as bromosulfophthalein (BSP) and taurocholic acid. Intravenous administration of SM-SOD markedly inhibited the reflow-induced decrease in transhepatic transport of these ligands. Thiobarbituric acid - reactive metabolites (TBAR) in the liver and plasma remained unchanged during occlusion and reflow, while TBAR in the bile increased significantly. Intravenous injection of SM-SOD inhibited the reflow-induced increase in biliary TBAR. Xanthine oxidase activity in plasma also increased during occlusion and reflow by an SM-SOD-inhibitable mechanism. Polymorphonuclear leukocyte-dependent chemiluminescence of the peripheral blood remained unchanged during occlusion, but increased markedly with time after reflow. SM-SOD also inhibited the increase in chemiluminescence almost completely. These and other results suggested that the superoxide radical and/or its metabolite(s) might play an important role in the pathogenesis of the reflow-induced liver injury and that SM-SOD might be useful for studying the mechanism for tissue injury caused by oxygen toxicity. PMID- 2306118 TI - Selective expression of cytochrome P450 isozymes by 4-n-alkyl methylenedioxybenzenes in rat lung cells. AB - Rat lung preparations were analyzed for cytochrome P450 expression as a function of pretreatment with 1 mmol/kg/day of various substituted n-alkyl methylenedioxybenzenes (MDBs). Lung P450s were quantitated by Western blotting and visualized by immunocytochemical techniques using polyclonal antibodies directed against P450IA1/IA2 and P450IIB1/IIB2. Results demonstrated that n-hexyl and n-octyl-MDB (but not n-butyl-MDB) increased P450IA1 in lung microsomes (50 pmol/mg microsomal protein) compared to untreated controls and n-butyl-MDB treated animals (6 pmol/mg). However, treatment with all of these MDBs concomitantly decreased P450IIB1 in rat lung microsomes, from 40 pmol/mg in untreated control lungs to below the detection limit of this method (less than 2 pmol/mg). In vitro metabolism assays with rat lung microsomes, utilizing 7,12 dimethylbenz[a]anthracene as substrate, confirmed the increase in P450IA1 by selected MDBs and the concomitant decrease of catalytically active P450IIB1. Immunocytochemistry of rat lungs with these same IgGs indicated selective cellular responses. n-Hexyl-MDB (but not n-butyl-MDB) increased P450IA1-like immunoreactivity, but the increase was specifically localized to Clara cells. Immunocytochemical results further showed that P450IIB1-like immunoreactivity disappeared entirely from alveolar type II cells, yet appeared unchanged in Clara cells relative to untreated controls. Increases in P450IA1 due to treatment with n-hexyl-MDB were associated with increases in P450IA1 mRNA as indicated by Northern blot experiments. In contrast, the decreased levels of P450IIB1, consequent to treatment with n-alkyl-MDBs, were not associated with altered levels of pulmonary P450IIB1 mRNA as determined by Northern blotting and solution hybridization assays. These results imply that n-alkyl-MDBs regulate pulmonary cytochromes P450 by both transcriptional and post-transcriptional mechanisms. PMID- 2306119 TI - Characterization of two monoclonal antibodies specific for lacto-series type 1 chain Gal beta 1----3GlcNAc-terminal structures. AB - Murine monoclonal antibodies, TE-1 and TE-3, generated by immunization with a biosynthetic reaction product containing a terminal Gal beta 1----3GlcNAc structure have been produced and found to react specifically with underivatized type 1 chain lacto-series carbohydrate structures. Detailed analysis of these antibodies, both IgM, indicates two differing classes of epitope specificity. Antibody TE-1 was found to bind preferentially to longer chain carbohydrate structures containing a terminal Gal beta 1----3GlcNAc disaccharide, indicating that optimal antibody binding involved more than recognition of this disaccharide. In contrast, antibody TE-3 was found to bind strongly carbohydrate structures containing terminal Gal beta 1----3GlcNAc structures irrespective of chain length. Modification of core chain structures by addition of fucose and/or sialic acid residues completely abolished antibody binding with either antibody. TLC immunostaining of neutral glycolipids isolated from a variety of human colonic adenocarcinoma cell lines indicated intensely stained bands, particularly with antibody TE-3, which correlated with the level of expression of type 1 chain based glycolipid derivatives. These antibodies are applied to the detailed study of the regulation of synthesis of lacto-series type 1 chain based carbohydrate structures. PMID- 2306120 TI - Fumarase: viscosity dependence of the kinetic parameters. AB - Fumarase catalyzes the reversible, stereospecific hydration of fumarate to form L malate. We have determined the viscosity dependence of V/K and V in both the forward and the reverse directions at pH 6.9 in the absence and presence of several viscosogenic reagents. V/K for fumarate hydration decreases with increasing concentrations of glycerol and sucrose, but is unaffected by increasing concentrations of the polymeric viscosogen polyethyleneglycol (av MW, 10,000 da). V/K for malate dehydration similarly decreases with increasing concentrations of both glycerol and sucrose, but is unaffected by increasing concentrations of polyethylene glycol. Equilibrium constants, calculated from the ratio of V/K values for malate dehydration and fumarate hydration at various concentrations of glycerol, closely match the experimentally determined equilibrium constants at the same concentrations of glycerol. Both experimental and calculated equilibrium constants decrease with increasing concentrations of viscosogens. V/K for the dehydration of (-)-tartrate, a poor substrate, is unaffected by increasing concentrations of glycerol. Analysis of the microviscosity dependence of malate dehydration and fumarate hydration suggests that both substrates bind at diffusion-limited rates. The viscosity dependence of substrate and product dissociation steps may also contribute to the viscosity dependence of V/K values for both substrates. The viscosity dependence of the maximal velocities argues that product dissociation steps are rate-limiting and diffusion controlled. PMID- 2306121 TI - Binding of nucleoside triphosphates, inorganic phosphate, and other polyanionic ligands to the N-terminal region of rat brain hexokinase: relationship to regulation of hexokinase activity by antagonistic interactions between glucose 6 phosphate and inorganic phosphate. AB - Mg2(+)-chelates of several nucleoside triphosphates were shown to increase the inactivation of rat brain hexokinase (ATP:D-hexose-6-phosphotransferase, EC 2.7.1.1) by 0.6 M guanidine hydrochloride, with ATP-Mg2+ having the greatest effect; unchelated forms did not significantly affect inactivation. Since catalytic activity has been associated with the C-terminal half of the molecule, these results were interpreted as indicating a destabilization of this C-terminal region by binding of these chelates to the substrate nucleotide sites, with the particular effectiveness of ATP-Mg2+ reflecting the specificity for this species as a phosphoryl donor. These compounds were also shown to bind to the N-terminal half of the enzyme, as judged by their ability to protect against denaturation by guanidine hydrochloride and subsequent digestion with trypsin. Both free and Mg2(+)-chelated forms afforded protection, with the unchelated nucleotides being most effective; a preference for ATP was seen only with the chelated forms. Thus, it was concluded that the N-terminal half of hexokinase contains a relatively nonspecific nucleotide binding site, distinct from the substrate nucleotide site previously shown to reside in the C-terminal half. On the basis of this same ability to protect the N-terminal half against denaturation and proteolysis, several other polyanionic ligands were shown to bind to this region of the molecule. These included inorganic phosphate, its analogs, sulfate and arsenate, and its homologs, pyrophosphate and tripolyphosphate. All of these anionic ligands were also shown to antagonize inhibition by the glucose 6-phosphate (Glc 6-P) analog, 1,5-anhydroglucitol 6-phosphate. The allosteric site for binding of Glc-6-P has previously been shown to reside in the N-terminal half of the molecule, and it is suggested that the antagonism of inhibition by Glc-6-P (or its analog) by these anionic ligands results from interaction with an anion binding site for which the 6-phosphate group of inhibitory hexose 6-phosphates must compete. A model depicting possible relationships between ligand binding sites on brain hexokinase, and how their interactions might lead to observed regulatory properties, is developed based on these and previous studies of ligand binding as well as evidence that mammalian hexokinases (Mr 100,000) have evolved by duplication and fusion of a gene coding for an ancestral hexokinase with Mr 50,000 and which, like the mammalian enzyme, was sensitive to inhibition by Glc-6 P. PMID- 2306122 TI - Isolation and characterization of one isoform of actin from cultured soybean cells. AB - Cultured soybean cells (SB-1 cell line) were plasmolyzed and lyophilized. Extraction of the dried powder and fractionation yielded a polypeptide with the following key properties: (a) it has a molecular weight of approximately 45,000 and an isoelectric point of approximately 5.9; (b) it is immunologically cross reactive with rabbit antibodies affinity purified against the Mr 45,000 polypeptide of calf thymus actin; (c) it is eluted from a DEAE-cellulose column at the same ionic strength as Acanthamoeba actin; (d) it yields peptide maps, after limited proteolysis with V8 protease, similar if not identical to those of rabbit muscle actin; and (e) it binds specifically to deoxyribonuclease I. These molecular and binding properties indicate that we have purified one isoform of actin from soybean cells. PMID- 2306123 TI - Developmental regulation of hepatic testosterone hydroxylases: simultaneous activation and repression of constitutively expressed cytochromes P450 in senescent rats. AB - The aging process is generally associated with marked decreases in the activities of numerous enzymes as well as lower levels of sex hormones such as testosterone. We therefore examined testosterone metabolism in liver microsomes from individual 3- and 24-month-old male rats. Although the old rats exhibited lower 16 alpha-, 6 beta-, and 2 alpha-hydroxylase activities than the young rats, the old rats had a higher 7 alpha-hydroxylase activity. Immunoquantitation of P450a, a known 7 alpha hydroxylase, showed that the level of this protein was elevated in the old rats, and was correlated with 7 alpha-hydroxylase activity. The mRNA for P450a was measured with a cDNA probe and its level was fivefold higher in the old rats, whereas levels of mRNA coding for a 6 beta-hydroxylase P450 were markedly decreased. The increased expression of cytochrome P450a demonstrates that the observed common decrease in cytochrome P450-catalyzed activities with senescence is not a universal phenomenon. Thus, constitutive expression of specific cytochrome P450 genes is repressed or activated in senescent rats. PMID- 2306124 TI - Isolation and characterization of the rat glutathione S-transferase Yb1 subunit gene. AB - We have isolated and characterized a rat liver glutathione S-transferase Yb1 subunit gene. DNA sequence analysis of the Yb1 subunit gene indicates that it comprises eight exons separated by seven introns and spans approximately 5.0 kb. The transcription initiation site has been mapped by primer extension experiments. Transcription begins at a guanine residue 29 nucleotides downstream from a "TATA" sequence. The DNA sequences of all exons and some introns share significant sequence identity with the corresponding exons and introns in the Yb2 subunit gene characterized by Tu and co-workers [J. Biol. Chem. 263, 11389-11395 (1988)]. The isolation and characterization of the glutathione S-transferase Yb1 gene will allow for a detailed analysis of regulatory elements required for transcriptional regulation of this gene. PMID- 2306125 TI - The dimeric form of phosphoenolpyruvate carboxylase isolated from maize: physical and kinetic properties. AB - Phosphoenolpyruvate carboxylase purified from maize was a homodimer of molecular weight 200 kDa and was readily converted to a tetrameric form in the presence of Mg2+ plus PEP or Mg2+ alone. During the assay, the enzyme activity increased with time, reaching a steady state after a discernible lag, suggesting its hysteretic nature. The hystereses was not due to oligomerization of the enzyme as the lag time tau was independent of the enzyme concentration and the lag was not abolished on preincubation with 25 mM Mg2+, the condition under which the enzyme existed in tetrameric form. Nevertheless, the lag could be abolished on preincubating the enzyme with PEP plus Mg2+, indicating that the hystereses is due to a PEP plus Mg2(+)-induced slow transition of the enzyme to an activated state during the catalysis. During steady state, the enzyme showed cooperative kinetics for PEP and Mg2+ at pH 7. It had two binding sites with nearly 10-fold difference in affinities for PEP and Mg2+. PMID- 2306126 TI - Hysteretic nature of phosphoenolpyruvate carboxylase isolated from maize. AB - The hysteretic nature of phosphoenolpyruvate carboxylase from maize was investigated at pH 7 by (a) transient kinetic studies, (b) kinetics of inhibition by 2-PG, a structural analog of PEP, and (c) effect of 2-PG on equilibrium binding of Mg2+. The lag time as a function of substrate concentration was nonlinear with an oblique asymptote. During steady state, cooperative kinetics for Mg2+ was changed to hyperbolic kinetics in the presence of 2-PG. Studies on the equilibrium binding of Mg2+ with the help of an external fluorescent probe, 8 anilino-6-naphthalinosulfonate showed that the hyperbolic binding of Mg2+ was changed to cooperative binding in the presence of 2-PG. On the basis of these results along with the results presented in the preceding paper, a fully concerted sequential model with subunit interaction is proposed for PEPC. PMID- 2306128 TI - Essential residues in lysolecithin:lysolecithin acyltransferase from rabbit lung: assessment by chemical modification. AB - The inhibition of lysolecithin:lysolecithin acyltransferase by several specific reagents was studied. Diisopropyl fluorophosphate (DFP) completely inhibited both activities at a concentration of 4 mM. Activity was not protected by substrate and the enzyme showed a change in circular dichroism spectrum upon treatment with inhibitor. Phenylmethanesulfonyl fluoride, another serine-specific reagent, did not inhibit either hydrolysis or transacylation. Therefore, we suggest that DFP does not modify an active serine in the catalytic site. p-Hydroxymercury benzoate and N-ethylmaleimide (NEM) abolished both activities of the enzyme. The presence of substrate partially protected against inactivation. Far-uv CD spectrum of NEM modified enzyme revealed no changes in protein structure. The existence of two classes of essential cysteine residues was deduced from kinetics of NEM inactivation. Both classes differ in NEM reactivity and also in their participation in the catalytic mechanism. A tyrosine-specific reagent, tetranitromethane, also inhibited hydrolysis and transacylation, following first order kinetics. The partial protection by substrate suggested the possible existence of essential tyrosines near the active site. At pH 5.0 N-ethoxycarbonyl 2-ethoxy-1,2-dihydroquinoline inactivated hydrolysis but not transacylation. However, both of them remained unchanged at pH 6.5. The substrate prevented the loss of hydrolytic ability. Therefore, a carboxyl residue participating just in the catalytic mechanism of hydrolysis is proposed. PMID- 2306127 TI - Selective induction of cytochrome P450 isozymes in rat liver by 4-n-alkyl methylenedioxybenzenes. AB - To examine the structural requirements of cytochrome P450 induction by 4-n-alkyl substituted methylenedioxybenzenes (MDBs), rats were treated in vivo with a series of MDBs that differed in alkyl carbon side-chain length (0, 1, 2, 3, 4, 5, 6, or 8). Expression patterns of specific P450 isozymes were evaluated with Western and Northern blotting, enzymatic assays, and solution hybridization assays. As determined by carbon monoxide difference spectroscopy, maximal hepatic induction of total P450 content occurred when rats were treated with MDB derivatives with alkyl chain lengths of five or six carbons. However, maximum induction of the specific P450s--P450IA1, P450IIB1, and P450IIB2--occurred with n hexyl-MDB. In contrast to effects observed with phenobarbital, treatment with MDBs resulted in higher levels of P450IIB2 than of P450IIB1 in rat hepatic microsomes. Western blot quantitation of MDB-induced hepatic P450IIB1 and P450IIB2 apoenzymes did not correlate to measured levels of the corresponding P450 mRNAs. In fact, P450IIB1 and P450IIB2 apoenzyme levels were consistently lower than expected based on Northern blot and solution hybridization measures of the respective mRNAs. These data suggest that the n-alkyl-MDBs effect increases in levels of hepatic P450 in a complex manner, producing accumulation of P450 mRNAs concomitant with alterations in processes regulating steady-state levels of P450 apoenzyme. PMID- 2306129 TI - Chlorophyll-free chromoplasts from daffodil contain most of the enzymes for chlorophyll synthesis in a highly active form. AB - Chromoplasts isolated from chlorophyll-free daffodil flowers utilize in vitro delta-aminolevulinic acid (ALA) as precursor for the synthesis of large amounts of at least nine different products. Their identification as intermediates of the chlorophyll biosynthetic pathway demonstrates the presence of the majority of the respective enzymes in this nongreen plastid preparation. Porphobilinogen synthase was investigated more closely and found to be similar in its properties to the corresponding enzyme from other plastid sources. Protoporphyrin IX was also accepted as a substrate by chromoplast homogenate; here, as in the case of ALA as a substrate, Mg-protoporphyrin IX monomethyl ester was the last product formed. Formation of the isocyclic chlorophyll ring was not observed. PMID- 2306130 TI - Postnatal circulatory adaptation in healthy term and preterm neonates. AB - Thirty seven healthy infants (18 born at full term and 19 preterm) were studied serially with cross sectional and Doppler echocardiography to compare their postnatal circulatory adaptation. Pulmonary artery pressure was assessed by its inverse relationship with the ratio of pulmonary artery time to peak velocity and right ventricular ejection time measured from Doppler waveform. Patency of the ductus arteriosus and interatrial shunting were assessed by imaging and Doppler ultrasound. The ratio rose after birth in all infants; it rose more slowly in the preterm infants. After 6 hours of age the mean was significantly less in the preterm group, the greatest difference being between 25 and 36 hours. By 73 to 96 hours the difference was no longer significant. There was a trend towards later ductal closure in the preterm infants but this was not significant. Atrial shunting level varied, but some left to right shunting was seen in all infants satisfactorily studied. Pulmonary artery pressure seems to fall more slowly after preterm birth even in the absence of respiratory problems, but ductal shunting persisting for more than three days is unusual in healthy preterm infants. PMID- 2306131 TI - Birthweight ratio and outcome in preterm infants. AB - The association between birthweight ratio and outcome was investigated in 429 infants born before 31 weeks' gestation. Birthweight ratio was calculated in each case as birth weight divided by mean birth weight for gestation (from reference data). It was shown that a given ratio corresponded to the same birth centile across the gestational age range studied; a ratio of 0.8 corresponding to the 10th centile. There was a linear relationship between birthweight ratio and requirement for mechanical ventilation and postneonatal mortality. Birthweight ratio was also strongly and linearly related to body weight, length, and head circumference at 18 months' corrected age. Overall, there was no association between this ratio and neurodevelopmental outcome to 18 months. However, the subgroup with the largest weights for gestation (birthweight ratio greater than or equal to 1.1), had significantly higher language subscores than all the other children. Our data show that conventional dichotomous categorisation of preterm infants into small or appropriate for gestation is inadequate when exploring the association between size for gestation and outcome. PMID- 2306132 TI - Pupillary diameter and reaction to light in preterm neonates. AB - The pupil controls the amount of light entering the eye. We have examined both the time course for the development of the light reflex and pupil diameter before and after this event in 50 neonates. The pupillary light reflex was absent in all neonates of less than 30 weeks' gestational age, it gradually developed from this age and by 35 weeks it was present in all. Several possible mechanisms that may explain the onset of this reflex are considered. Before the onset of the pupil reflex mean horizontal pupillary diameter was 3.46 mm compared with 3.02 mm after the reflex development. We have estimated the amount of light reaching the retina (retinal irradiance) for preterm neonates and although it is less than that known to cause retinal damage in animals, further research is necessary to determine whether early light exposure has an adverse or beneficial effect on the immature visual system. PMID- 2306133 TI - Behavioural states in normal mature human fetuses. AB - Behaviour was studied by real time ultrasound in a group of 80 low risk fetuses between 36 and 42 weeks' gestation. There was close linkage of fetal eye movements, somatic movements and heart rate pattern reflecting three different states. Quiescence (state 1F) was characterised by no eye movements, no somatic movements except for the occasional startle, and a fetal heart rate pattern with little baseline variability. There were two active states: state 2F characterised by continuous eye movements, frequent bursts of somatic movements, and wide baseline variability with accelerations with movement, and state 4F characterised by continuous eye movements with almost continuous somatic movements and a sustained tachycardia. These fulfilled criteria for three of four behavioural states previously described in human fetuses. Cycling of quiescent and active states occurred in 77 (96%) of the fetuses within 100 minutes of starting the recording. 2F was the commonest behavioural state, being seen 58% of the time. 1F was seen 30% of the time, and 4F 9% of the time. During the remaining 3% of observation time the behavioural state was indeterminate. PMID- 2306134 TI - Access for peritoneal dialysis in neonates and infants. AB - A new catheter for peritoneal dialysis in neonates and infants was used on 28 occasions in 17 patients. Advantages over other catheters included easy safe introduction over a guide wire, absence of early leakage of dialysate, and the ability to change the catheter without creating a second abdominal wound. PMID- 2306136 TI - Neonatal pneumomediastinum with isolated mitral obstruction. AB - While mediastinal air accumulation in the ventilated newborn is usually a benign entity, tension pneumomediastinum can embarrass both respiratory and cardiac function. A case of isolated left ventricular inflow obstruction caused by a pneumomediastinum in a premature infant is described that resolved with high frequency ventilation. The development of pneumomediastinum and haemodynamic compromise in a premature infant warrants echocardiographic examination. PMID- 2306135 TI - Dexamethasone and infection in preterm babies: a controlled study. AB - To find out if the use of steroids affected the incidence of infection in babies who were nursed in the neonatal intensive care unit for nine weeks or more, 24 preterm babies who had received a three weeks course of dexamethasone (0.6 mg/kg/day, reducing to 0.3 mg/kg/day after a week, and 0.15 mg/kg/day after two weeks) were compared with 18 preterm babies who had not been so treated. No differences were found in the incidence or pattern of septicaemia or other bacteriologically proved infections between the groups. Of 57 episodes of septicaemia, 44 (77%) were caused by coagulase negative staphylococci. PMID- 2306137 TI - Getting the most mileage from donated hearts. PMID- 2306138 TI - J. Maxwell Chamberlain memorial paper. Sternal wound complications after isolated coronary artery bypass grafting: early and late mortality, morbidity, and cost of care. AB - Of 6,504 consecutive patients who underwent isolated coronary bypass grafting in 1985 to 1987, 72 (1.1%) patients experienced sternal wound complications. Ten patients (14%) with wound complications died of multi-system failure. Only the patients with negative cultures fared well; of the bacterial culture categories, polymicrobial infection carried the worst prognosis. Effects of recurring infection were seen throughout the first year. Patients, grouped according to conduits received, experienced these wound complication rates: vein grafts only, 11/1,085 (1.0%); one internal thoracic artery, 38/4,073 (0.9%); and bilateral internal thoracic artery grafts, 23/1,346 (1.7%). There were no significant differences in wound complication rates between primary and reoperation patients or among conduit groups. By logistic regression analysis, the relative risk for patients with diabetes and bilateral internal thoracic artery grafting was 5.00 (95% confidence interval, 2.4 to 10.5). Operation time as a continuous variable increased the relative risk of wound complication 1.47 times per hour (1.3 to 1.7); obesity, 2.90 times (1.8 to 4.8); and blood units as continuous variable, 1.05 times per unit (1.01 to 1.10). Bilateral internal thoracic artery grafting in nondiabetic patients carried no greater risk of wound complication than that in patients with vein grafts only or with one internal thoracic artery graft. PMID- 2306140 TI - Seventeen-year experience with bilateral internal mammary artery grafts. AB - The internal mammary artery (IMA) is being recognized as the conduit of choice for myocardial revascularization. From January 1972 through June 1988, 1,087 patients received bilateral IMA and supplemental vein grafts. There were 917 men (84.4%) and 170 women (15.6%) with a mean age of 62.4 years (range, 29 to 84 years). Three hundred ninety-four patients (36.2%) had unstable angina, and 194 (17.8%) had left main coronary artery stenosis greater than 50%. In all, 3,741 coronary grafts were performed, with a mean of 3.4 per patient. Hospital mortality was 2.7% (29 patients). Hospital complications included reoperation for bleeding, 19 patients (1.7%); sternal infection, 16 patients (1.5%); respiratory failure, 35 patients (3.2%); perioperative myocardial infarction, 22 patients (2.0%); and stroke, 20 patients (1.8%). Post-operative arteriography in 53 patients (mean postoperative time, 53.0 months) showed that 92.1% (58/63) of the left IMA and 84.9% (45/53) of the right IMA grafts were patent. Follow-up was completed on 1,058 hospital survivors. There were 82 late deaths (7.8%). The actuarial survival for patients discharged from the hospital was 80.0 +/- 3.2% (plus or minus standard error of the mean) at 10 years and 60.0% +/- 5.0% at 15 years. At follow-up, 866 patients (90.3%) were asymptomatic and in New York Heart Association class I and 68 (7.1%) were in class II. This longitudinal analysis demonstrates that bilateral IMA grafting has a low operative risk and provides excellent long-term functional improvement and survival. PMID- 2306139 TI - Routine use of the left internal mammary artery graft in the elderly. AB - Left internal mammary artery (LIMA) grafts have better long-term patency rates than do saphenous vein grafts and result in improved late survival. The present study was undertaken to assess the results of LIMA grafting in the elderly. From 1980 through 1988, 723 patients 70 years of age or older had isolated coronary artery bypass grafting performed. During the first 5 years, only 11% of the elderly patients received LIMA grafts, whereas 86% having coronary artery bypass grafting since 1985 had LIMA grafts. Since 1986, LIMA use in the elderly has become routine, with 92% of patients receiving internal mammary artery grafts. During the first 5 years, elderly patients had a hospital mortality rate of 9.3%. Since 1985, the hospital mortality rate fell to 5.5%. In addition, the occurrence of major surgical complications was either unchanged or reduced in patients receiving LIMA grafts. Furthermore, late follow-up indicates a significantly improved 4-year survival rate in patients with internal mammary artery grafts compared with those without: 86 +/- 0.02% versus 77 +/- 0.03% (p less than 0.01). Analysis of multiple potential risk factors for early mortality was performed using multiple logistic regression and late survival using the Cox proportional hazards model. Although unmeasured predictor variables may confound retrospective analyses, LIMA grafting appears to be an independent predictor both of improved early and late survival. PMID- 2306141 TI - Results of internal thoracic artery grafting over 15 years: single versus double grafts. AB - One hundred consecutive patients who had coronary artery bypass grafting using both internal thoracic arteries (ITAs) and saphenous veins, operated on during a 3-year period between 1972 and 1975, have been compared retrospectively with a series of 100 patients operated on during the same period who had one ITA graft along with saphenous vein grafts. The two groups were similar with respect to age, sex, risk factors for coronary artery disease, angina class, extent of coronary artery disease, left ventricular function, number of coronary bypass grafts performed, and completeness of revascularization. Single ITA operative mortality was 2% and double ITA, 9% (p = NS). The mean follow-up of hospital survivors was 14.4 +/- 2.7 years; all but 7 patients had follow-up for at least 10 years. At 13 years, the actuarial patency of the right ITA was 85% and the left ITA, 82%. These data strongly suggest a survival benefit for patients with double ITA grafts among hospital survivors (74% versus 59%; p = 0.05). Patients receiving two ITA grafts had a significant freedom from subsequent myocardial infarction (75% versus 59%, p less than 0.025), recurrent angina pectoris (36% versus 27%, p less than 0.025), and subsequent total ischemic events (32% versus 18%, p less than 0.01). These data also suggest improved freedom from coronary artery interventional therapy (percutaneous transluminal coronary angioplasty and reoperation) when two ITA grafts were used. These results support the use of bilateral internal thoracic artery grafting in selected patients. PMID- 2306142 TI - Risks of bilateral internal mammary artery bypass grafting. AB - Although use of one internal mammary artery (IMA) for coronary artery bypass grafting does not appear to be associated with increased risk, the results with both IMAs are less certain; the potential for a higher incidence of sternal wound infection as a result of devascularization of the sternum is a major concern. During a 42-month interval ending July 1988, 1,566 patients had coronary artery bypass grafting alone or in combination with other procedures: 633 received only vein grafts, 687 had unilateral IMA grafting, and 246 had bilateral IMA grafting. The IMA patients were younger, were more often male, had better cardiac function, and underwent fewer emergent, urgent, or combined procedures than the patients receiving vein grafts (p less than 0.05). Thirty-day mortality was lower among the IMA patients (unilateral IMA group, 2.8%; bilateral IMA group, 3.7%; and vein graft group, 7.9%; p = 0.001). With the exception of sternal wound problems, occurrence rates for postoperative complications among the IMA patients did not differ significantly from or were lower (p less than 0.05) than those among the patients with vein grafts. Sternal infections occurred with greater frequency among the bilateral IMA patients (6.9%) than among the unilateral IMA (1.9%) or vein graft (1.3%) patients (p = 0.001). By univariate analysis, obesity, diabetes, bilateral IMA grafting, and need for prolonged (greater than 48 hours) mechanical ventilation were associated with a significantly higher incidence of sternal infection (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306143 TI - HLA histocompatibility affects cardiac transplant rejection and may provide one basis for organ allocation. AB - Prospective human lymphocyte antigen (HLA) typing is not performed for heart transplantation, and the relation between HLA matching and cardiac graft rejection is unclear. Recipient and donor HLA matching were analyzed retrospectively in 51 patients undergoing orthotopic cardiac transplantation. Immunosuppression was based on cyclosporine and prednisone. During the mean follow-up of 34 months (range, 16 to 63 months), the 46 operative survivors had an average of 3.95 rejection episodes (range, zero to 11 episodes). Twenty-one patients had steroid-resistant rejection requiring treatment with polyclonal or monoclonal antithymocyte globulin. Human lymphocyte antigen typing was available for 44 patients, and antigens were grouped in broad specificities. Patients with two or more HLA-A or HLA-B matches had a reduced number of rejection episodes (3/10 versus 19/34) and a lower incidence of steroid-resistant rejection (1/10 versus 18/34; p = 0.01). Inclusion of HLA-DR matches did not alter the findings. There was a strong correlation between the increased frequency of rejection and the incidence of steroid-resistant rejection (p less than 0.0001). Four of six late deaths occurred in patients with steroid-resistant rejection; four were due to acute rejection and two to graft atherosclerosis. Although not currently done, prospective HLA matching is feasible with present typing methods. Our results suggest a rationale for prospective histocompatibility testing in cardiac transplantation with allocation of donor hearts to patients with two or more HLA matches. PMID- 2306144 TI - Dynamic aortomyoplasty to assist left ventricular failure. AB - The efficacy of skeletal muscle contractile force to augment left ventricular function has been demonstrated experimentally and clinically by the cardiomyoplasty procedure. Another approach in biomechanical cardiac assistance is the use of electrostimulated skeletal muscle in an extracardiac position. We describe an autologous counterpulsating device using the native ascending aorta as a ventricular chamber wrapped by an electrostimulated latissimus dorsi muscle flap (LDMF). This model avoids thrombotic complications observed in skeletal muscle neo-ventricles associated with prosthetic chambers. In 8 goats, a right LDMF was transferred to the thoracic cavity by removal of the second rib. In 4 goats, the diameter of the aorta was enlarged by surgical implantation (using lateral clamping) of an autologous pericardial patch. The LDMF was wrapped around the ascending aorta and electrostimulated using an external diastolic pulse generator connected to a sensing myocardial lead and to LDMF pacing electrodes. Hemodynamic studies were performed (left ventricular, aortic, and pulmonary artery pressures and rate of rise of left ventricular pressure). The LDMF diastolic counterpulsation was performed using a burst of 30 Hz, with a delay from the R wave adjusted to provide optimal diastolic augmentation. Percent increase in the subendocardial viability index was calculated during unassisted and assisted cardiac cycles (1:2) at baseline and after acute heart failure induced by the administration of high doses of propranolol hydrochloride (3 mg/kg intravenously). Diastolic aortic counterpulsation by the stimulated LDMF resulted in a significant improvement in the subendocardial viability index both at baseline and after induced cardiac failure in both groups, though the increase was greater in the group with aortic enlargement. PMID- 2306145 TI - Computerized activation sequence mapping of the human atrial septum. AB - To delineate the propagation of electrical activation in the atrial septum, atrial epicardial and atrial septal maps were recorded intraoperatively using a 156-channel computerized mapping system in 12 patients during sinus rhythm (n = 10), supraventricular tachycardia associated with septal pathways in Wolff Parkinson-White syndrome (n = 3), atrioventricular (AV) node reentrant tachycardia (n = 4), and atrial flutter (n = 5). The epicardial and septal data were recorded simultaneously from 156 atrial electrodes, digitized, analyzed, and displayed as isochronous maps on a two-dimensional diagram of the atria. During sinus rhythm, the activation wave fronts propagated most rapidly along the large muscle bundles of the atrial septum. During supraventricular tachycardia associated with Wolff-Parkinson-White syndrome, the earliest site of retrograde atrial activation usually corresponded to the position of atrial insertion of the septal pathways. However, the earliest site of activation during orthodromic supraventricular tachycardia was different from that during ventricular pacing in 1 patient with a posterior septal accessory pathway localized by the epicardial mapping study. The data document the rationale for dividing the ventricular end of the accessory pathways (ie, the endocardial technique) rather than the atrial end (ie, the epicardial technique) in patients with Wolff-Parkinson-White syndrome. During AV node reentrant tachycardia, atrial activation data suggested that atrial tissue lying outside the confines of the anatomical AV node is a necessary link in this common arrhythmia. Thus, these atrial septal maps explain why surgical dissection, or properly positioned small cryolesions placed in the region of the AV node, can ablate AV node reentrant tachycardia without altering normal AV node function. The maps recorded during atrial flutter suggest the importance of the atrial septum as one limb of a macroreentrant circuit responsible for the arrhythmia, and imply that atrial flutter is amenable to control by surgical techniques. These studies demonstrate the details of normal atrial septal activation, the importance of the atrial septum in a variety of different atrial arrhythmias, and the basis of and potential for surgical ablation of the most common types of supraventricular arrhythmias. PMID- 2306146 TI - Diaphragmatic plication for unilateral diaphragmatic paralysis: a 10-year experience. AB - Unilateral paralysis of the diaphragm due to nonmalignant disease is an uncommon disorder previously thought to have benign implications. Some patients, however, experience dyspnea and orthopnea with impairment of pulmonary function. Unilateral diaphragmatic plication was performed on 17 patients (16 men and 1 woman with a mean age of 53.7 years [range, 28 to 74 years]) during the last 10 years. Preoperatively each patient was shown to have paradoxical movement of the paralyzed diaphragm on sniffing and to have a reduction in forced vital capacity and lung volumes. These reductions were greater when the patient was in the supine position. All patients had moderate hypoxemia (mean arterial oxygen tension, 73.1 +/- 10.9 mm Hg). Plication was performed by imbricating the diaphragm in layers through a thoracotomy incision. After plication, all patients showed both subjective and objective improvement. Six patients were reassessed 5 or more years after plication (range, 5 to 7 years), and the improvement was maintained. Diaphragmatic plication is a safe and effective procedure for adult patients with dyspnea due to unilateral diaphragmatic paralysis; furthermore, the initial improvement is maintained. PMID- 2306147 TI - Surgical treatment of automatic atrial tachycardias. AB - From 1979 to 1989, 18 patients were seen in the Electrophysiology Service, Duke University Medical Center, with automatic atrial tachycardia. There were 8 male and 10 female patients with a mean age of 28.1 +/- 2.9 years. Electrophysiological mapping localized automatic foci to right atrial sites (14 patients) and left atrial sites (4 patients). Depending on origin of the focus, patients were further diagnosed as having either chronic ectopic atrial tachycardia or inappropriate sinus tachycardia. Of the 15 patients with chronic ectopic atrial tachycardia, 6 responded to medical treatment; in 9, the tachycardia was not adequately controlled. Six of them were referred for surgical intervention. All 3 patients with inappropriate sinus tachycardia underwent operative therapy. In the surgical group of patients with chronic ectopic atrial tachycardia, all 6 had a tachycardia-induced cardiomyopathy with ejection fractions ranging from 14% to 27% (mean ejection fraction, 21% +/- 2.7%). Surgical techniques used (alone or in combination) included an isolation procedure in 1 patient, cryoablation in 4 patients, and excision of atrial appendages or portions of atrial free walls in 7. Normal sinus rhythm developed in all surgical patients except 1 patient who had intractable congestive heart failure preoperatively and died of this condition and stroke. The overall success rates for medical and surgical therapy were 33.3% and 88.9%, respectively (p less than 0.01). Long-term follow-up was possible for 7 (87.5%) of 8 patients 3 to 7 years after operation. All patients with chronic ectopic atrial tachycardia were cured, but only 1 of 3 patients with inappropriate sinus tachycardia was in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306149 TI - Management of neonatal critical pulmonic stenosis in the balloon valvotomy era. AB - We evaluated our recent experience with management of neonatal critical pulmonic stenosis and intact ventricular septum between 1982 and 1988. Thirty-nine patients (aged less than 3 months) were treated initially by operation (group A, n = 19) or with balloon pulmonary valvotomy (group B, n = 20). Patients in group A were younger (5 +/- 1.3 versus 18 +/- 4 days in group B) (mean +/- standard error of the mean) and had a greater degree of hypoxia (oxygen tension, 55 +/- 4 versus 80 +/- 6 mm Hg) (p less than 0.05 for all variables). Ten patients in group A and 8 patients in group B had right ventricular hypoplasia, based on an angiographically determined index. Balloon pulmonary valvotomy was attempted in 20 patients at the time of the initial catheterization but was unsuccessful in 9 owing to inability to catheterize the hypoplastic right ventricular outflow tract (n = 8) and to recurrent infundibular stenosis (n = 1). Patients with failed balloon valvotomy were subsequently operated on within 24 hours. The early operative mortality (less than 30 days) was 25% (7 of 28); one death (9%) occurred after successful balloon valvotomy owing to associated critical aortic stenosis. The early postoperative gradient was 20 +/- 2 mm Hg; the post-balloon valvotomy gradient was 18 +/- 3 mm Hg. We conclude that balloon pulmonary valvotomy yields good results in patients with critical pulmonary stenosis with essentially normal-sized right ventricle, whereas surgical pulmonary valvotomy is required for patients with right ventricular hypoplasia. PMID- 2306148 TI - Experience with univentricular support in mortally ill cardiac transplant candidates. AB - Between July 1987 and March 1989, 11 patients underwent left ventricular support with the Novacor left ventricular assist system irrespective of apparent degree of right ventricular failure. The first 2 patients died of multisystem organ failure while on support. All the remaining patients survived the support period, and actuarial survival after transplantation was 100% at 6 months and 89% at 1 year. In no patient did bacterial infection develop during support or after transplantation. Right ventricular ejection fraction before implantation of the left ventricular assist system was lower than 15% in 6 of 8 patients, yet it increased twofold during left ventricular support. The need for excessive inotropic support (2 patients) or temporary (four days) mechanical right ventricular support (2 patients) while on the left ventricular support system appeared to be related to elevated pulmonary vascular resistance during support in association with large preimplantation ventricular volumes. It appears that even patients with compromised right ventricular performance can be supported long term with a left ventricular assist device. Patients with elevated pulmonary vascular resistance may require temporary right ventricular support. PMID- 2306150 TI - Reduction of complement activation during bypass by prime manipulation. AB - Complement activation is believed to be of importance in the development of complications arising after cardiopulmonary bypass. The effect on complement activation of priming the extracorporeal circuit with crystalloid alone, crystalloid plus albumin, or crystalloid plus the plasma expander polygeline was assessed in 36 patients undergoing coronary artery operations with cardiopulmonary bypass using a bubble oxygenator. Activation of the alternative and common complement pathways was monitored before, during, and after the bypass period by measuring concentrations of factor B and its fragment Ba and C3 and its fragment C3d. Complement activation occurred in all three groups of patients, with no difference between the crystalloid and crystalloid-albumin groups. In contrast, Ba fragment concentrations were persistently and significantly lower during and after bypass in the polygeline group, denoting reduced complement activation. C3d levels also showed a tendency to be lower in this group. Our results indicate that addition of polygeline to the priming solution reduces complement activation. Because complement activation is associated with morbidity after cardiopulmonary bypass, addition of polygeline to the priming solution may offer an inexpensive method of reducing morbidity after cardiopulmonary bypass. PMID- 2306151 TI - Esophageal carcinoma in young patients. AB - The clinicopathological features of esophageal carcinoma were examined from the viewpoint of age differences in a study of 364 consecutively treated patients. The three groups studied were: group I, aged less than 49 years; group II, aged between 50 and 69 years; and group III, aged more than 70 years. There were no significant differences among the three groups with regard to sex ratio, site and length of the lesion, gross types, histological grade, depth of tumor invasion, vessel permeation, lymph node metastasis, TNM classification, incidence of incomplete resection, or crude actuarial 5-year survival curves. The malignant potentiality of the esophageal carcinoma in young patients did not differ from that in older patients in terms of deoxyribonucleic acid distribution pattern. The only difference clearly evident between young and older patients was the number of hospital deaths due to complications: That of the young patients was significantly lower than that of the older patients (p less than 0.05). Esophageal carcinoma in persons aged less than 50 years appeared to behave biologically like the same neoplasm in older people, whereas gastric and colorectal carcinomas behave differently in various age groups. PMID- 2306152 TI - First human use of the Hemopump, a catheter-mounted ventricular assist device. AB - The Hemopump, a catheter-mounted, temporary ventricular assist device, consists of an external electromechanical drive console and a disposable, intraarterial axial-flow pump (21F). Power is transmitted percutaneously to the pump by a flexible drive shaft within the catheter. The device is positioned in the left ventricle by way of the femoral artery approach or through the ascending aorta. Blood is drawn from the left ventricle through the transvalvular inlet cannula and pumped into the aorta. As of December 1988, the Hemopump had successfully supported the circulation of 7 patients (5 men, 2 women) ranging in age from 44 to 72 years (mean age, 59 years) and suffering from cardiogenic shock (cardiac index less than 2.0 L/min/m2). Indications for use included failure to be weaned from cardiopulmonary bypass in 4 patients, acute myocardial infarction in 1, severe cardiac allograft rejection in 1, and donor heart failure in 1. Duration of support ranged from 26 to 113 hours (mean, 66 hours). Although 5 patients demonstrated transient hemolysis, none experienced infection, thrombosis, or vascular injury. Hemodynamic variables improved in all patients during support by the device. As of December 1988, 5 of the 7 patients were alive more than 30 days after support had been discontinued, and 3 of these patients were discharged from the hospital. On the basis of our initial clinical results, the Hemopump, which does not require a major surgical procedure for insertion, provides effective, temporary circulatory support in patients with potentially reversible cardiac failure. PMID- 2306153 TI - Intracavitary melanoma of the left atrium. AB - A 32-year-old man was seen with shortness of breath and increasing fatigue. Echocardiography revealed an intracavitary mass occupying the entire left atrium. The lesion was resected using cardiopulmonary bypass and found to be a large malignant melanoma. This case represents the rare occasion in which antemortem diagnosis of malignant melanoma within left atrium permitted successful palliative surgical resection. The patient is alive and active 6 months after operation. PMID- 2306154 TI - Chiari network entrapment of thromboemboli: congenital inferior vena cava filter. AB - Pulmonary emboli and a right atrial thrombus enmeshed in a Chiari network developed concurrently in a 69-year-old man. The network perhaps functioned as an inferior vena cava filter preventing massive pulmonary embolus. Chiari network should be considered in the differential diagnosis of a right atrial mass and the presence of pulmonary emboli should suggest surgical removal. PMID- 2306155 TI - Group F streptococcal empyema from aspiration of a grass inflorescence. AB - A previously healthy 15-year-old boy was seen with a loculated right lower lobe empyema. Group F beta-hemolytic streptococci were cultured from the pleural fluid. Surgical intervention was required. An unsuspected aspirated grass inflorescence and a bronchopleural fistula were discovered during a decortication procedure. PMID- 2306156 TI - Coronary artery bypass grafting with unanticipated fibrosing mediastinitis. AB - Coronary artery bypass grafting in the setting of superior vena caval obstruction due to unanticipated fibrosing mediastinitis is described. Intraoperative decisions regarding the management of this unusual patient are discussed. PMID- 2306157 TI - Hemorrhage control after removal of surgically implanted intraaortic balloon pump. AB - Surgically implanted intraaortic balloon catheters have a substantial potential to cause hemorrhage on percutaneous removal. Because of the unacceptably high incidence of uncontrollable hemorrhage in patients in a life-threatening situation, a new percutaneous surgical modification allowing removal of these balloons with low blood loss has been devised and has proved highly successful in hemorrhage control. PMID- 2306158 TI - Sequel of the internal mammary artery as a systemic-to-pulmonary artery shunt. PMID- 2306159 TI - Pericardial flap. PMID- 2306161 TI - One-stage operation for chronic empyema. PMID- 2306160 TI - Aortic homograft for aortic valve endocarditis. PMID- 2306162 TI - Alternate technique for biopsy in lung transplantation patients. PMID- 2306163 TI - Preservation of normal cognitive functioning in elderly subjects with extensive white-matter lesions of long duration. AB - Although deep white-matter brain lesions are seen on magnetic resonance imaging in about one third of elderly subjects, their clinical significance is not known. In 1984, we studied three retired teachers who had extensive deep white-matter brain lesions on magnetic resonance imaging, yet functioned cognitively at an above-average level. Blinded review of 1981 computed tomographic scans revealed patchy white-matter lucencies for two of the subjects. Repeated magnetic resonance imaging in 1987 showed that the deep white-matter brain lesions were at least as extensive as in the initial study. One subject had developed renal failure, while the other two continued to function at a high level with no evidence of cognitive decline or psychiatric or neurologic impairment. The presence of extensive deep white-matter brain lesions for up to 7 years in two subjects whose cognitive, behavioral, and neurologic functioning is unimpaired suggests that deep white-matter brain lesions do not necessarily indicate a clinically significant central nervous system disease process. PMID- 2306164 TI - Memory complaints and impairment in normal, depressed, and demented elderly persons identified in a community survey. AB - Normal, depressed, and demented elderly persons who were identified by means of a community survey were asked to assess their memories and to complete a battery of memory tests. Depressed elderly persons reported memory problems more often than normal subjects and reported indecisiveness, impaired concentration, and mental slowing more often than demented subjects. However, memory complaints and memory performance correlated poorly in the normal and depressed groups. Normal and demented elderly persons who reported memory problems achieved higher scores on a series of questions about depression than those who denied memory problems. PMID- 2306165 TI - Multiple pains and psychiatric disturbance. An epidemiologic investigation. AB - We assessed multiple pain conditions and their association with affective disturbance, somatization, and psychological distress based on questionnaire data from a probability sample of 1016 enrollees of a large health maintenance organization. Respondents were asked about the presence of five pain conditions and were classified empirically in terms of dysfunctional chronic pain status based on pain severity, pain persistence, and pain-related disability days. Logistic regression analyses revealed a highly significant association between number of pain conditions reported and elevated levels of somatization as measured by the Symptom Checklist 90-Revised. Individuals with two or more pain conditions were at elevated risk of an algorithm diagnosis of major depression, while persons with a single pain condition did not differ from persons with no current pain conditions. Number of pain conditions reported was a better predictor of major depression than were important measures of pain experience, including pain severity and pain persistence. PMID- 2306166 TI - Relationship between anxiety disorders and depressive disorders in patients with cerebrovascular injury. AB - The interaction between anxiety disorder and major depressive disorder in patients with cerebrovascular lesions was examined in a controlled, 2 x 2 study design. A consecutive series of 24 patients who met criteria for major depression only were compared with 6 patients who met criteria for both major depression and generalized anxiety disorder, and 45 patients who did not meet criteria for either major depression of generalized anxiety. Among patients with positive computed tomographic scans, the anxious-depressed group (n = 19) showed a significantly higher frequency of cortical lesions, while patients with major depression only (n = 15) had a significantly higher frequency of subcortical (basal ganglia) strokes. No significant between-group differences were found in other variables, such as demographic variables, familial and personal history of psychiatric disorders, and neurologic deficits. These findings suggest that, in this mostly black, low-socioeconomic-status population, cortical vs subcortical lesion location may play an important role in determining whether severe anxiety occurs in patients with post-stroke major depression. PMID- 2306167 TI - Familial transmission of simple phobias and fears. A preliminary report. AB - Preliminary data from a blind direct interview family study indicate a significantly higher risk for simple phobia among first-degree relatives (n = 49) of simple phobic probands (who had no other anxiety disorder) as compared with first-degree relatives (n = 119) of never mentally ill controls (31% vs 11%, relative risk = 3.3). Female relatives were more likely to be affected than male relatives (48% vs 13%), though this difference did not reach conventional significance in an age-corrected analysis. Significant between-group differences were not found in risks for (1) other anxiety, affective, and substance abuse disorders, and (2) simple irrational fears that did not meet disorder criteria. The results suggest that simple phobia is a highly familial disorder that does not transmit increased risk for other phobic or anxiety disorders. The specificity of increased risk among the relatives of simple phobics is consistent with the distinction between simple phobia, social phobia, and agoraphobia. However, complete delineation of the transmissional relationship between these illnesses requires assessment of the extent to which risk for simple phobia can be transmitted by individuals with other phobic or anxiety disorders. Replication of these preliminary findings in larger clinically and epidemiologically selected samples is needed. PMID- 2306168 TI - GABAmimetics: a new class of antidepressant agents? PMID- 2306169 TI - Lithium treatment effect on serotonin function. PMID- 2306170 TI - What is left of attention in schizophrenia? PMID- 2306171 TI - An update on the Helsinki Influenza Project. PMID- 2306172 TI - College of American Pathologists Conference XVI on AIDS and the pathologist: foreword. PMID- 2306173 TI - College of American Pathologists Conference XVI. AIDS and the pathologist. August 9-11, 1989. Proceedings. PMID- 2306174 TI - Transfusion of the patient with acquired immunodeficiency syndrome. AB - Cytopenias are commonly found in patients infected with human immunodeficiency virus. Thrombocytopenia due to peripheral destruction of platelets is an early manifestation, normocytic anemia and neutropenia are late manifestations. Transfusions are required when symptoms become severe. Chemotherapy of patients with the acquired immunodeficiency syndrome (AIDS) is also cytotoxic and further contributes to the transfusion requirement. Patients with AIDS receiving treatment with zidovudine, in particular, have a high transfusion requirement. Empirically, many centers irradiate blood products transfused to AIDS patients to prevent possible graft-vs-host reaction in the immunologically compromised recipient. Attempts to correct the deficiency of helper T cells with lymphocyte transfusion and marrow transplantation have so far been ineffective. Similarly, therapeutic trials to treat this disease by apheresis of virus-bearing cells has been ineffective and has, therefore, been abandoned. PMID- 2306175 TI - Sabbatical leave for surgeons. PMID- 2306176 TI - Mammographic second opinions prior to biopsy of nonpalpable breast lesions. PMID- 2306177 TI - Seroma prevention using fibrin glue in a rat mastectomy model. AB - Seromas are a frequent complication of mastectomy (17% to 53%) in humans and are correlated to skin flap elevation, lymphovascular interruption, and drainage into surgically created potential spaces. The use of intraoperative topical fibrin glue to reduce morbidity in rats undergoing radical mastectomies has been evaluated. A model consistently producing seromas was developed by radical mastectomy and lymphadenectomy in the Sprague-Dawley rat. A fibrin glue application procedure was tested using this model. The double-blinded protocol called for spray application of saline or fibrin glue to mastectomy wounds followed by sequential inspection and necropsy on postoperative days 5, 8, 11, and 14. Topical fibrin glue was shown to be statistically significant in decreasing the presentation of seromas following a radical mastectomy in the Sprague-Dawley rat. PMID- 2306178 TI - Patterns of failure in anorectal melanoma. A guide to surgical therapy. AB - Anorectal melanoma is an aggressive tumor with a reported 5-year survival rate of 6%. Recommendations for local surgical therapy vary from local excision to abdominoperineal resection. Therapy, patterns of failure, and survival were retrospectively examined in 32 patients with anorectal melanoma. Twenty-six patients were treated surgically, 14 with abdominoperineal resection and 12 with local excision. Local recurrence occurred less frequently in patients undergoing abdominoperineal resection (4 [29%] of 14) compared with patients undergoing local excision (7 [58%] of 12) but developed concomitantly with distant or regional metastasis in all but 2 of the 11 patients whose operations failed locally. Inguinal nodal disease developed in 15 patients (47%). Pelvic nodal disease became apparent in only 2 patients (7%). There was no difference in overall survival between the two surgically treated groups (median survival, 19.5 months for patients treated with abdominoperineal resection vs 18.9 months for patients treated with local excision). Therefore, local excision is recommended when technically feasible since these patients eventually succumb to metastasis regardless of surgical therapy. PMID- 2306179 TI - Isolated limb perfusion for localized melanoma of the extremity. A matched comparison of wide local excision with isolated limb perfusion and wide local excision alone. AB - The therapeutic efficacy of isolated limb perfusion in patients with localized melanoma of the extremity remains controversial. We compared patients treated at the University of Texas M.D. Anderson Cancer Center, Houston, with wide local excision and isolated limb perfusion using either melphalan or imidazole carboxamide with a group matched for prognostic factors from the University of Alabama at Birmingham and the University of Sydney (Australia) who were treated with wide local excision alone. No significant difference in disease-free or overall survival rates was found between patients treated with wide local excision with adjuvant isolated limb perfusion or wide local excision alone. However, a subset of patients with thicker lesions (greater than 2.0 mm) treated with wide local excision and isolated limb perfusion using melphalan had a significant improvement in both disease-free and overall survival rates. These data suggest that isolated limb perfusion using melphalan may improve survival rates in selected patients with localized melanoma of the extremity who are at increased risk for local and regional micrometastases, and justifies the continued study of this treatment approach in prospective clinical trials. PMID- 2306180 TI - Prognosis of thick cutaneous melanoma of the trunk and extremity. AB - The records of 129 patients with thick cutaneous melanoma of the trunk or extremity treated at Memorial Sloan-Kettering Cancer Center, New York, NY, between 1974 and 1984 were reviewed with the aim of defining prognostic variables. All primary lesions invaded subcutaneous fat, were Clark level V, or of a Breslow thickness of 4.0 mm or greater. Treatment in all cases was by wide excision with or without split-thickness skin graft; all patients underwent regional lymph node dissection. Overall survival rate for the group was 47% at 5 years and 36% at 10 years. Factors independently predictive of survival were pathologic negative nodes (71% at 5 years compared with 28% for pathologic positive nodes) and extremity site (58% at 5 years compared with 33% for truncal site). Patients with node-negative thick cutaneous melanoma of the extremity had a 5-year survival rate of 82%. Patients with node-positive truncal thick cutaneous melanoma had a 5-year survival rate of only 8%. There was no difference between the 5-year survival rate of patients with node-negative truncal thick cutaneous melanoma, 52%, and patients with node-positive thick cutaneous melanoma of the extremity, 42%. Nearly half of the patients with thick cutaneous melanoma of the extremity and trunk present with locoregional disease, at a stage when an aggressive surgical approach is warranted. Prognostic variables of pathologic nodal status and site identify patients at risk for early systemic failure. PMID- 2306181 TI - Stage B prostate adenocarcinoma. Flow cytometric nuclear DNA ploidy analysis. AB - Over a 16-year period (1966 to 1981), 349 patients underwent radical retropubic prostatectomy for pathologic stage B adenocarcinoma of the prostate. Nuclear DNA content was measured by flow cytometry on available archival material of 283 patients. Two hundred sixty-one patients (92%) had high-quality histograms. The ploidy distribution was as follows: DNA diploid, 177 (68%); DNA tetraploid, 74 (28%); and DNA aneuploid, 10 (4%). The average follow-up was 9.4 years. At the time of follow-up, 53 patients (20%) within the study group had developed tumor progression: 22 local, 23 systemic, and 8 both. The ploidy distribution of the population that developed tumor progression was 27 DNA diploid (51%), 16 DNA tetraploid (30%), and 10 DNA aneuploid (19%). This ploidy distribution is significantly different from that found for the nonprogression group with stage B disease. Overall, 31% of patients with DNA nondiploid tumors had tumors that progressed compared with 15% of patients with DNA diploid tumors. All (100%) DNA aneuploid tumors progressed. The DNA ploidy distribution of all pathologic stage B prostate cancers differs significantly from that found in more advanced stages (C and D1) previously reported for the same time interval. However, the ploidy distribution of stage B tumors that progressed closely resembles that of the stage C and D1 tumors. These results further support the working hypothesis that nuclear DNA content has marked prognostic significance for patients with adenocarcinoma of the prostate. It seems to us that analysis of ploidy by flow or static cytometry will become an essential tool for treating patients with localized prostate cancer. PMID- 2306182 TI - Inhibition of sialic acid incorporation prevents hepatic metastases. AB - It has been hypothesized that the metastatic capacity of tumors may be correlated with hypersialylation of the cell surface. We used a novel inhibitor of sialic acid incorporation, KI-8110, to determine the effect of depletion of cell surface sialic acid on the metastatic behavior of three human colorectal cancer cell lines, in which hepatic seeding was related to tumor cell differentiation. Treatment of tumor cells with KI-8110 prior to intrasplenic injection prevented liver colonization. Total cellular sialic acid was reduced, as was that of the cell surface. Secreted forms of carcinoembryonic antigen also were depleted of sialic acid by this treatment. These data show that depletion of sialic acid from cell surface glycoconjugates reduces the incidence of hepatic metastases from human colorectal primary tumors and adds to the mounting evidence of the importance of sialic acid in determining the biological behavior of tumor cells. PMID- 2306183 TI - Segmental mastectomy without radiotherapy for T1 and small T2 breast carcinomas. AB - We describe 111 patients with invasive breast cancer treated by segmental mastectomy at the University of Miami (Fla) since 1975. Postoperative adjuvant radiotherapy was recommended as optional rather than mandatory to 64 of these patients based on small (2.5 cm or less) primary tumor size, adequate resection margins, no lymphatic or vascular invasion within the segmental mastectomy specimen, and minimal associated in situ cancer. Fifty-one of these patients elected to forego postoperative adjuvant radiotherapy. At 72 months median follow up, relapse occurred in the ipsilateral breast in three patients who elected to forego postoperative adjuvant radiotherapy (6% by Kaplan-Meier analysis). Retrospective pathologic review revealed that tumor grade may also be important in determining whether postoperative adjuvant radiotherapy is necessary following segmental mastectomy. These data suggest that postoperative adjuvant radiotherapy may not be required in every patient treated by segmental mastectomy. Further studies to define which patients can be spared the inconvenience, expense, and potential morbidity of postoperative adjuvant radiotherapy are warranted. PMID- 2306184 TI - Intraoperative radiation therapy and hyperthermia. Morbidity and mortality from this combined treatment modality for unresectable intra-abdominal carcinomas. AB - This is a report of a phase I trial of intraoperative radiation therapy in combination with intraoperative hyperthermia for the treatment of locally advanced, unresectable intra-abdominal carcinomas. Using an ultrasound transducer system specifically designed for intraoperative applications, 19 patients have been successfully treated, demonstrating the feasibility of this combination modality. The morbidity (58%) and mortality (11%) rates reported in this series are comparable to rates reported in series of similar patients receiving intraoperative radiation therapy alone. There is still a great need for considerable technological development to enable the use of intraoperative hyperthermia to treat large, complexly shaped intra-abdominal tumors, and phase II and III trials of this combination treatment modality should be performed. PMID- 2306185 TI - Comparison of magnetic resonance imaging and computed tomography in the preoperative staging of rectal cancer. AB - Nineteen patients with middle and lower rectal carcinomas were operated on, with abdominoperineal resection in 10 patients, lower anterior resection with coloanal anastomosis in 6 patients, and colorectal anastomosis in 3 patients. The distance of the lower margin of the tumor to insertion of the levator ani on the rectal wall was correctly evaluated by computed tomography in 12 (63%) of 19 patients and by magnetic resonance imaging in 13 (68%) of 19 patients, while digital examination correctly assessed the distance in 15 (79%) of 19 patients. Computed tomography and magnetic resonance imaging were unable to assess extension through the rectal wall. No significant difference was observed between computed tomography and magnetic resonance imaging in assessing extension to the perivesical fat, adjacent organs, pelvic side wall, or lymph nodes. According to the TNM classification, magnetic resonance imaging correctly staged 74% (14/19) of carcinomas, while computed tomography correctly staged 68% (13/19). PMID- 2306186 TI - Achievements of physical therapy in patients after modified radical mastectomy compared with quadrantectomy, axillary dissection, and radiation for carcinoma of the breast. AB - Flexion of the shoulder, abduction, and external rotation in 90 degrees abduction are impaired after operations for breast cancer. We compared postoperative range of motion in 27 patients who underwent modified radical mastectomy and 21 patients who underwent quadrantectomy with axillary dissection and radiation therapy. The patients in the quadrantectomy group demonstrated a significantly higher range of flexion on postoperative day 1 and the day of suture removal. After 3 months, all patients had regained their preoperative range of flexion, with no difference between the groups. The better compliance of the quadrantectomy group to physical therapy may indicate that they suffer less pain and require a briefer or less intensive course of physical therapy. PMID- 2306187 TI - Growth delay in postburn pediatric patients. AB - Dampened height and weight velocities have been observed in our postburn pediatric population. To validate this phenomenon, the medical records of 80 patients who had sustained a greater than 40% total body surface area burn, were older than 2 years of age at the time of the burn, and were at least 1 year post burn were reviewed. All patients were treated with early excision of the burn wound within 72 hours of injury and received standard post burn resuscitational and nutritional support. Admission height and weight plots were within normal distribution parameters. Yearly growth velocities were calculated for up to 3 years after the burn. Despite adequate nutritional support and maximal exercise and/or long-bone stresses, a profound growth arrest was noted during postburn year 1, which slowly resolved to near normal distribution by postburn year 3. This retrospective study demonstrates that severe thermal injury is associated with a growth delay in the pediatric population. The exact cause of this phenomenon remains unknown. PMID- 2306188 TI - Surgery for nonpalpable breast lesions. AB - Nonpalpable lesions detected on mammograms were localized in 475 women between 1976 and 1988 by means of the spot method. A malignant neoplasm was noted in 149 patients (31%), including 69 (33%) of 206 with clusters of microcalcifications, 16 (41%) of 39 with calcifications associated with densities and 64 (28%) of 230 with nonpalpable masses. Infiltrating lesions were present in 89 (60%) of 149 patients. Among women with infiltrating lesions who had axillary dissection, 14 (21%) of 67 had positive nodes. In younger women, microcalcifications were more likely to represent neoplasms, masses frequently represented invasive tumors. Among patients with invasive malignant neoplasms who had calcifications, 39% had positive axillary lymph nodes. Spot localization, rather than monitoring, seems appropriate in young women with microcalcifications suggestive of malignant neoplasms and older patients with nonpalpable masses to achieve earlier and more effective treatment of biologically significant occult neoplasms. PMID- 2306189 TI - The retained surgical sponge following intra-abdominal surgery. A continuing problem. AB - The surgical sponge retained following intra-abdominal surgery is a continuing problem. Despite precautions, the incidence of this problem is grossly underestimated. During the past 10 years, we have treated four patients with this problem. The presentation of a retained surgical sponge is highly variable, as is the time before the onset of symptoms. The clinical presentation, predisposing factors, and management are presented as well as guidelines for prevention. PMID- 2306190 TI - Effect of the peroxisome proliferator perfluorodecanoic acid on growth and lipid metabolism in Sprague Dawley rats fed three dietary levels of selenium. AB - The possible interrelationships between the effects of dietary selenium and perfluorodecanoic acid (PFDA) on growth and lipid metabolism were studied in the male Sprague Dawley rat. Rats were divided into groups and placed on diets containing three levels of selenium (0.04, 0.2, and 1.0 ppm as sodium selenite). Two weeks later, half the rats in each group received a single 35 mg/kg IP injection of PFDA in corn oil, while their pair-fed companion received only vehicle. Rats injected with PFDA stopped gaining weight, and weighed less than pair-fed controls, despite equal food intakes. Two weeks following PFDA administration the rats were killed and plasma cholesterol and triglycerides, and liver peroxisomal enzyme activities were quantified. In contrast to other peroxisome proliferators, PFDA increased plasma triglycerides while decreasing plasma cholesterol. The rate of peroxisomal fatty acid beta-oxidation was decreased, even though the activity of fatty acyl-CoA oxidase, the first enzyme in the peroxisomal fatty acid beta-oxidation pathway, was increased. Dietary selenium, other than increasing the liver to body weight ratio, did not alter growth or lipid metabolism. This study demonstrates, for the first time, the existence of a "non-hypotriglyceridemic" peroxisome proliferator - PFDA. PMID- 2306192 TI - Tissue accumulation of lipoprotein associated toxaphene in normo- and hypolipidemic mice. AB - Normo- and hypolipidemic mice were given a single i.v. injection of 14C-toxaphene associated with low density lipoprotein (LDL), high density lipoprotein (HDL) or dimethyl sulfoxide (DMSO). The tissue distribution of radioactivity was studied 20 min and 4 h after the application. In the normolipidemic mice at 20 min postinjection there was high uptake of the 14C-toxaphene preparations in the liver and adrenals followed after 4 h by a redistribution to the adipose tissues. In the hypolipidemic mice, proportionally less label accumulated initially in the liver and adrenals while more radioactivity was seen in the kidneys and heart. The radioactivity then redistributed to the liver with a very small uptake in the adipose tissue compared to the normolipidemic mice after 4 h. The results indicate that changes in the lipid pattern, e.g. hypolipidemic conditions, may influence the tissue distribution of lipophilic xenobiotics. PMID- 2306191 TI - Alterations in tissue Pb distribution and hematopoietic indices during advanced age. AB - The inevitable degenerative processes accompanying advanced age suggest that senescent organisms might exhibit differences in toxicokinetics or an altered manifestation of toxic effects. This hypothesis was tested in the present experiment which compared tissue distribution and hematopoietic indices in groups of adult (8 months) and old male Fischer-344 rats (16 months) exposed to concentrations of 0, 250 or 500 ppm lead (Pb) acetate in drinking water for 7 months. A group of young (weanling) rats was included as a partial comparison. Blood lead (PbB), zinc protoporphyrin (ZPP) and urinary delta-aminolevulinic acid levels were determined after both 3 and 7 months of exposure. Organ weights, tissue Pb concentrations and urinary excretion of Pb, calcium, copper, and zinc were examined after 7 months of exposure. Tissue Pb distribution was markedly altered in old rats: bone and kidney Pb were reduced; liver Pb was substantially increased, even though PbB levels in adult and old rats were comparable at both measurement intervals, as was urinary Pb excretion at 7 months. Pb-induced elevation of ZPPs exhibited differential changes between 3 and 7 months: values in adults declined while levels in old rats increased or remained unchanged. These findings show that the responses of adult rats to Pb do not predict those of older rats and indicate the need for further characterization and elaboration of mechanisms of toxic effects with advanced age. PMID- 2306193 TI - Comparative teratogenicity of three retinoids: the arotinoids Ro 13-7410, Ro 13 6298 and Ro 15-1570. AB - Three retinoids of the arotinoid series, namely the free carboxylic acid Ro 13 7410, its ethyl ester Ro 13-6298, and the new arotinoid ethyl sulfone Ro 15-1570, were tested for their embryotoxic and teratogenic activity in rats. The retinoids were administered orally on either day 9 or 13 of gestation. Treatment on day 9 of gestation resulted mainly in malformations of the head and the trunk; whereas, on day 13 limb malformations were prominent. Ro 13-7410 and Ro 13-6298 were about 1000 times more embryotoxic and teratogenic than retinoic acid but induced a similar malformation pattern to retinoic acid. In contrast, the sulfur-containing arotinoid Ro 15-1570 was active at similar dose levels to retinoic acid but caused a peculiar malformation pattern on day 13 of gestation. This finding supports the hypothesis that the arotinoid ethyl sulfone Ro 15-1570 has unique biological properties, inducing no bone toxicity in adult rats and distinctly affecting limb development. PMID- 2306194 TI - Course of ATP depletion in hydrazine hepatotoxicity. AB - The effect of hydrazine on ATP levels has been investigated in rats in vivo and in hepatocytes in vitro. Hydrazine was found to cause a dose-dependent depletion of hepatic ATP in vivo 3 h after dosing. In isolated hepatocytes in vitro hydrazine also caused a concentration-dependent depletion of ATP which preceded cytotoxicity as indicated by loss of cell viability. The ATP depletion in isolated hepatocytes was also significant at a concentration of hydrazine which was not cytotoxic. Attempts to determine hepatic ATP depletion in vivo over time using topical 31P NMR were confounded by the effects of the thiopentobarbitone used to anaesthetise the animals. This was found to ameliorate the effects of hydrazine on ATP depletion but potentiate the lethality of hydrazine. Consequently, although ATP depletion was detected in some hydrazine-treated animals, this was only observed in animals which subsequently died. The results indicate that ATP depletion may underlie the hepatotoxicity of hydrazine. PMID- 2306195 TI - Activation and toxicity of bromobenzene in nasal tissue in mice. AB - Autoradiography of mice injected i.v. with bromobenzene-14C (BB; 25 mumol/kg body wt) revealed a high concentration of non-volatile metabolites in the olfactory mucosa and in the glands around the maxillary sinuses. As determined with solvent extracted tissue sections, there was a high level of irreversibly bound metabolites in the Bowman's glands in the olfactory mucosa, while the level of bound metabolites was low in the glands around the maxillary sinuses. Histopathological examination of the nose region of mice given a single i.p. dose of unlabelled BB (greater than or equal to 4.8 mmol/kg body wt) revealed degeneration and necrosis of the glands of Bowman. Degenerative changes in the olfactory epithelium were also observed. Moreover, focal degeneration and necrosis were found in the lateral nasal glands (greater than or equal to 4.8 mmol/kg body wt). Cyst-like dilatation of acini was observed in the lateral nasal glands and in the maxillary glands located around the maxillary sinus. Incubation of BB (26 microM) with a homogenate prepared from the olfactory mucosa revealed an irreversible binding, which clearly exceeded that of the liver. It is suggested that BB is activated in situ to a cytotoxic metabolite that reacts with the glands of Bowman. The specific toxicity observed in the lateral nasal glands correlated with a high concentration of non-volatile but extractable metabolites in these glands. PMID- 2306196 TI - Distribution of three common chlorophenoxyacetic acid herbicides into the rat brain. AB - The distribution of three common 14C-labelled chlorophenoxyacetic acid herbicides (2,4-dichlorophenoxyacetic acid or 2,4-D, 2-methyl-4-chlorophenoxyacetic acid or MCPA, 2,4,5-trichlorophenoxyacetic acid or 2,4,5-T) into the different brain areas was studied in rats pretreated with toxic doses of the herbicides (238-475 mg/kg). Also, their binding to proteins in rat plasma was determined in vitro by increasing the concentrations of chlorophenoxyacetic acids in the incubate from 0 to 1 mg/ml. Both 2,4-D and MCPA pretreatments increased brain concentrations of 14C-labelled herbicides more markedly than 2,4,5-T pretreatments did. No essential differences were found in the distribution between the different brain areas. Protein-unbound fractions of 2,4-D and MCPA in the plasma were clearly higher than those of 2,4,5-T but the highest herbicide concentration increased the protein-unbound fraction of 2,4,5-T more (7-13-fold) than of 2,4-D and MCPA (5-fold). The results suggest that the greater increase in the penetration into the brain of 2,4-D and MCPA than of 2,4,5-T during their intoxication is due to some factors other than the changes in their binding to plasma proteins and mere enhanced diffusion through the blood-brain barrier. PMID- 2306197 TI - Reduced gluconeogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats. AB - The effect of a usually lethal dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 125 micrograms/kg) was studied on the conversion of 14C-alanine into 14C-glucose in male Sprague-Dawley rats by established procedures (determination of plasma alanine and blood glucose by enzymatic assays and isolation of 14C-alanine and 14C-glucose from whole blood by column chromatography). TCDD-treated rats converted significantly (p less than 0.05) less 14C-alanine into 14C-glucose than did their pair-fed or ad libitum-fed counterparts, indicating reduced gluconeogenesis as a result of TCDD treatment. This finding suggests that reduced gluconeogenesis in TCDD-treated rats contributed to the progressively developing, severe hypoglycemia observed in these animals. Corticosterone, a key hormone in gluconeogenesis, provides partial protection from TCDD-induced toxicity in hypophysectomized rats. Therefore, the conversion of 14C-alanine into 14C-glucose was also determined in hypophysectomized rats dosed with TCDD (125 micrograms/kg) and given corticosterone (25 micrograms/ml in drinking water). These rats also converted significantly (p less than 0.05) less 14C-alanine into 14C-glucose than did their pair-fed counterparts. However, in contrast to non-hypophysectomized TCDD-treated rats, these rats maintained marginal normoglycemia even at 64 days after dosing with TCDD, which suggests that the partial protective effect of corticosterone in hypophysectomized, TCDD-treated rats is unrelated to its effect on gluconeogenesis. The protection provided by corticosterone supplementation in TCDD toxicity is more likely due to reduced peripheral utilization of glucose enabling the animals to maintain marginal normoglycemia. PMID- 2306198 TI - Correlation between lipid peroxidation and morphological manifestation of paraquat-induced lung injury in rats. AB - Biochemical and morphological studies of rat lung were performed to determine the role of lipid peroxidation in the in vivo lung toxicity of paraquat. Two injections of 20 mg/kg paraquate were administered intraperitoneally every other day. While notable epithelial damage in the lungs was observed on the day after the second paraquat injection and progressed through the 5th day, the concentration of lipid peroxides in the rat lungs did not increase by the 3rd day after the injection. The lipid peroxide concentrations increased after the 5th day post-injection, and reached the maximum concentrations on the 7th day, when the damaged alveolar surface had been mostly repaired by regenerative pneumocytes. On the other hand, the delayed increase of lung lipid peroxides in paraquat-treated rats paralleled the increased number of macrophages in the lung, which reached maximum numbers on the 7th day. Glutathione peroxidase activity in the lungs also increased with a similar time course. Macrophages from the lungs contained a large amount of engulfed degradation products and cellular debris, and immunohistochemical study showed high glutathione peroxidase content on the 5th and 7th days. These results suggest that lipid peroxidation is a relatively late event in the in vivo paraquat-treated lung and that the delayed increase of lipid peroxides in the lungs occurs from the phagocytic activities of macrophages rather than from toxic cell injury. PMID- 2306199 TI - [The effect of the day of parturition in the technological cycle of maternity on the morbidity of diarrhea in lactating piglets]. AB - The study investigated the frequency of piglet diarrhoea from birth to weaning (33rd day) in a farrowing pigsty with 3 rows of boxes during 7 rearing cycles with 240 piglets each, always related to the day of birth in connection with the onset of the cycle. 3 groups were differentiated according to the day of birth: 3 and 4, 5, 6 and 7, based on the disposition of the sow. Also investigated was the position of the litters in the middle or one of the marginal rows of boxes of the pigsty. The germ density of the air during 2 cycles each of the rainy and dry seasons was investigated in the empty pigsty as well as after the 6th day of occupation by means of sedimentation in endo agar. A significant influence was found of the day birth (p less than 0.05) and of the interaction of row of boxes and day of birth (p less than 0.05) as well as the row of boxes and season (p less than 0.05) on the morbidity and mortality due to piglet diarrhoea. The higher levels occurred in the groups of animals born later and housed in the central row of boxes. The number of units forming colonies increased significantly (p less than 0.05) in 10 cm2/min samples on endo agar from the 0th to the 6th day of the cycle and reached 100% of the samples from which also E. coli K 88 was isolated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306200 TI - Reproductive performance of Friesian cows in Saudi Arabia. II. Resting and service interval, conception rate, and number of services per conception. AB - A comparative investigation was carried out on criteria for the reproductive performance (n = 590) of 114 imported and 86 locally born Friesian cows reared under semi-arid conditions in Saudi Arabia in 2 farms. No significant differences were found between the two groups as regards the resting time, first service to conception interval, service interval, conception rate, and insemination index. The conception rate was low (46%), and the insemination index-services per conception-was high (2.16). The season had no significant effect on the reproductive performance. Significant differences were found in the conception rate and insemination index of both groups between farms, with lower results for artificial insemination. Heat stress and adaption problems are seen as causing the low conception rate and insemination index. Measures for improving the reproductive performance of Friesian cows in Saudi Arabia are outlined. PMID- 2306201 TI - [The evaluation of fertility characteristics in hens using fluorescence microscopy]. AB - A method for the assessment of fertility in domestic hens is described. Vitelline membranes of fertilized eggs were coloured with fluorochrome DAPI, following which the DNA of sperms on these membranes has been examined with the help of fluorescence microscopy. After insemination with frozen semen there exist significant correlations between the number of sperms on the vitelline membranes on the one hand and 1) fertilization rates; 2) the length of fertile periods. Furthermore, it was observed that with higher numbers of sperms on the membranes, the length of the fertile periods tends to be shorter than with smaller numbers of sperm. PMID- 2306202 TI - [Anticholinergic medication in the dog before and during anesthesia]. AB - In clinical studies in dogs of all categories of age, which were predicted for surgical purposes under a combination anaesthesia with Fluanisone/Fentanyl/Nitrous oxide/Halothane, investigations after treatment with atropine or glycopyrrolate were performed. In experimental studies investigations about heart-rate and heart work (rate-pressure-product RPP) under different injection anaesthesia-methods (Fluanisone/Fentanyl/Metomidate, Climazolam/Fentanyl, Xylazine/l-Methadone) are performed. In the clinical studies many of the dogs produce elevated heart-rates after anticholinergic premedication. After special indicated treatment of dysrhythmias with glycopyrrolate or atropine in all cases normorhythmia can be achieved. An increase in heart rate during awaking time can be seen in non premedicated as well as in anticholinergic treated animals for a short period of time. In the experimental studies the anticholinergic treatment leads to increased heart rate and/or elevated arterial pressure, which produce an enormous increase in the rate pressure product and oxygen consumption. In conclusion a general anticholinergic premedication can not be recommended. Its use should be special indicated for bradycardia and/or dysrhythmias in the sense of AV-conduction disturbances. PMID- 2306203 TI - [Effect of the nutrition status on parturition in the cat]. AB - 37 Queens on the 64th day of pregnancy were evaluated for body condition and they were divided into three Groups. Group 1 4-5 kg body weight 4 Queens Group 2 5-6 kg body weight 14 Queens Group 3 6-7 kg body weight 19 Queens The Parameter: A means Age of the Queen in years, B means Gestation length in days, C means Number kitten born, D Stillbirths per Group, E Cesarean Section, were evaluated. Group 1 showed in the parameters D and E significant better performance when compared to Group 2 and 3. PMID- 2306204 TI - [Diseases of the extremities of swine in relationship to the floor condition with special reference to bursitis]. AB - In 2 pig farms, 102 sows kept in single ranging on plain concrete floor, 168 sows kept in single ranging on cast-iron grates and 27 fattening pigs kept in group penning on concrete slatted floors were repeatedly examined for the incidence of auxiliary synovial bursae (ASB). The clinical examination was completed by radiological, patho-anatomical and histological examinations of the rear legs. In sows, ASB were found on two prominences of the bones: on the latero-plantar area of the calcaneum and the fourth tarsal bone as well as on the plantar tarsal sesamoid bone. ASB on the rear legs were found in 41.2% of the sows kept on plain concrete floor and in 59.5% of the sows kept on cast-iron grates. The ASB of the sows kept on cast-iron grates were larger than those of the sows kept on plain concrete floor. In 49% of the sows kept on plain concrete floor the skin covering the ASB was reddened, in 45% of the sows kept on cast-iron grates it was covered with scab. Injury and necrosis of the skin as well as injury of the ASB themselves were found only in animals kept on cast-iron grates and made up 5% of the cases. In 30% of the cases, palpation of the ASB induced defensive movement. The palpation of ball-shaped, soft bursae more often caused defensive movement than did the palpation of flat-shaped, hard bursae. The occurrence of ASB was combined with kyphosis of the spine, false posture of the rear legs, dystasia, hyperextension of the fetlock, arthrosis of the ankle joint, and anomalies of the claws. In fattening pigs, the ASB were localized at the lateroplantar area of the calcaneum and the fourth tarsal bone as well as at the posterior surface of the calcaneum. At the end of the fattening period, ASB were detected in 26 out of 27 fattening pigs. All of the 48 ASB that were examined histologically showed signs of inflammation. In 30 cases the inflammation was chronic, in 18 cases it turned out to be florid. The results indicate that ASB cause pain during the developing phase and also in the chronic stage. PMID- 2306205 TI - Progress-curve equations for reversible enzyme-catalysed reactions inhibited by tight-binding inhibitors. AB - The rate equation for a tight-binding inhibitor of an enzyme-catalysed first order reversible reaction was used to derive two integrated equations. One of them covers the situations in which competitive, uncompetitive or non-competitive inhibition occurs and the other refers to the special non-competitive case where the two inhibition constants are equal. For these equations, graphical and non linear regression methods are proposed for distinguishing between types of inhibition and for calculating inhibition constants from progress-curve data. The application of the non-linear regression to the analysis of stimulated progress curves in the presence of a tight-binding inhibitor is also presented. The results obtained are valid for any type of 'dead-end'-complex-forming inhibitor and can be used to characterize an unknown inhibitor on the basis of progress curves. PMID- 2306207 TI - ADP evokes biphasic Ca2+ influx in fura-2-loaded human platelets. Evidence for Ca2+ entry regulated by the intracellular Ca2+ store. AB - Stopped-flow fluorimetric studies at 37 degrees C have shown that ADP, at optimal concentrations, can evoke Ca2+ or Mn2+ influx in fura-2-loaded human platelets without measurable delay. In contrast, the release of Ca2+ from intracellular stores is delayed in onset by about 200 ms. By working at a lower temperature, 17 degrees C, we have now shown that the rise in cytosolic calcium concentration ([Ca2+]i) evoked by ADP in the presence of external Ca2+ is biphasic. The use of Mn2+ as a tracer for bivalent-cation entry indicates that both phases of the ADP evoked response are associated with influx. The fast phase of the ADP-evoked rise in [Ca2+]i, which occurs without measurable delay at both 17 degrees C and 37 degrees C, is consistent with Ca2+ entry mediated by receptor-operated channels in the plasma membrane. The delayed phase, indicated by Mn2+ quench, is coincident with the discharge of the intracellular Ca2+ stores. Forskolin did not inhibit the fast phases of ADP-evoked rise in [Ca2+]i or Mn2+ quench, but completely abolished ADP-evoked discharge of the intracellular stores, the delayed phase of the rise in [Ca2+]i observed in the presence of external Ca2+ and the second phase of Mn2+ quench. The timing of the delayed event appears to be modulated by [Ca2+]i: the delayed phase of Mn2+ quench coincides with discharge of the intracellular stores in the absence of added Ca2+, but with the second phase of the ADP-evoked rise in [Ca2+]i in the presence of extracellular Ca2+. Similarly, blockade of the early phase of Ca2+ entry by SK&F 96365 further delays the second phase. It is suggested that a pathway for Ca2+ entry which is regulated by the intracellular Ca2+ store exists in platelets. This pathway operates alongside, and appears to be modulated by the activity of other routes for Ca2+ entry into the cytosol. PMID- 2306206 TI - Complete dissociation of gonadotropin receptor binding and signal transduction in mouse Leydig tumour cells. Obligatory role of glycosylation in hormone action. AB - Utilizing a clonal cell line of mouse testicular Leydig cells (MA-10 cells) the complete steroidogenic and other hormonal properties of chemically deglycosylated ovine lutropin (DG-LH) and human choriogonadotropin (DG-hCG) were evaluated. In these cells, with the LH receptor-steroidogenic mechanism tightly coupled and in which there are few, if any, spare receptors, both DG-LH and DG-hCG failed to elicit progesterone production, unlike fully glycosylated native LH and hCG. The receptor-binding activity of DG-LH and DG-hCG was 2-3 times that of LH and hCG in competition experiments with radiolabelled hormones. The typical phenomenon of rounding of MA-10 cells induced by LH and hCG was absent when cells were incubated with DG-LH or DG-hCG. This could be directly attributable to their failure to produce cyclic AMP as second messenger. DG-LH and DG-hCG inhibited cell shape changes and steroidogenesis caused by LH and hCG. The deglycosylated hormones were potent antagonists of the action of glycosylated hormones. Delaying DG-hCG (antagonist) addition for up to 1 h after initiation of hCG action was also very effective in preventing further activation of steroidogenesis. Similar effects were produced by addition of affinity-purified anti-hCG antibodies. In affinity cross-linking experiments, both hCG and DG-hCG bound to the same 90 kDa receptor. Studies with MA-10 cells thus provide unequivocal evidence that the presence of antennary sugars in LH and hCG (and perhaps in other similar hormones such as follicle-stimulating hormone and thyroid-stimulating hormone), is essential for signal transduction. Differences observed in the literature in other cellular systems may be attributed to differences in hormone-receptor effector coupling. PMID- 2306208 TI - Ca2(+)-sensitivity of inositol 1,4,5-trisphosphate-mediated Ca2+ release in permeabilized pancreatic acinar cells. AB - Hormonal and phorbol ester pretreatment of pancreatic acinar cells markedly decreases the Ins(1,4,5)P3-induced release of actively stored Ca2+ [Willems, Van Den Broek, Van Os & De Pont (1989) J. Biol. Chem. 264, 9762-9767]. Inhibition occurred at an ambient free Ca2+ concentration of 0.1 microM, suggesting a receptor-mediated increase in Ca2(+)-sensitivity of the Ins(1,4,5)P3-operated Ca2+ channel. To test this hypothesis, the Ca2(+)-dependence of Ins(1,4,5)P3 induced Ca2+ release was investigated. In the presence of 0.2 microM free Ca2+, permeabilized cells accumulated 0.9 nmol of Ca2+/mg of acinar protein in an energy-dependent pool. Uptake into this pool increased 2.2- and 3.3-fold with 1.0 and 2.0 microM free Ca2+ respectively. At 0.2, 1.0 and 2.0 microM free Ca2+, Ins(1,4,5)P3 maximally released 0.53 (56%), 0.90 (44%) and 0.62 (20%) nmol of Ca2+/mg of acinar protein respectively. Corresponding half-maximal stimulatory Ins(1,4,5)P3 concentrations were calculated to be 0.5, 0.6 and 1.4 microM, suggesting that the affinity of Ins(1,4,5)P3 for its receptor decreases beyond 1.0 microM free Ca2+. The possibility that an inhibitory effect of sub-micromolar Ca2+ is being masked by the concomitant increase in size of the releasable store is excluded, since Ca2+ release from cells loaded in the presence of 0.1 or 0.2 microM free Ca2+ and stimulated at higher ambient free Ca2+ was not inhibited below 1.0 microM free Ca2+. At 2.0 and 10.0 microM free Ca2+, Ca2+, Ca2+ release was inhibited by approx. 30% and 75% respectively. The results presented show that hormonal pretreatment does not lead to an increase in Ca2(+)-sensitivity of the release mechanism. Such an increase in Ca2(+)-sensitivity to sub-micromolar Ca2+ is required to explain sub-micromolar oscillatory changes in cytosolic free Ca2+ by a Ca2(+)-dependent negative-feedback mechanism. PMID- 2306209 TI - Localization of the essential histidine and carboxylate group in D-xylose isomerases. AB - D-Xylose isomerases from different bacterial strains were chemically modified with histidine and carboxylate-specific reagents. The active-site residues were identified by amino acid sequence analysis of peptides recognized by differential peptide mapping on ligand-protected and unprotected derivatized enzyme. Both types of modified residues were found to cluster in a region with consensus sequence: Phe-His-Asp-Xaa-Asp-Xaa-Xaa-Pro-Xaa-Gly, conserved in all D-xylose isomerases studied so far. These results are consistent with the recently published X-ray data of the enzyme active centre from Streptomyces rubiginosus showing hydrogen bond formation between Asp-57 and His-54 which locks the latter in one tautomeric form. A study of the pH-dependence of the kinetic parameters suggests the participation of a histidine group in the substrate-binding but not in the isomerization process. Comparison of the N-terminal amino acid sequences of several D-xylose isomerases further revealed a striking homology among the Actinomycetaceae enzymes and identifies them as a specific class of D-xylose isomerases. PMID- 2306211 TI - The purification and characterization of 3-dehydroquinase from Streptomyces coelicolor. AB - The enzyme 3-dehydroquinase was purified over 4000-fold to homogeneity from Streptomyces coelicolor. The subunit Mr estimated from polyacrylamide-gel electrophoresis in the presence of SDS was 16,000. The native Mr estimated by gel filtration on a Superose 6 column was 209,000, indicating that the enzyme is a large oligomer. The enzyme was found to be extremely thermostable. This stability, along with the structural and kinetic properties of the enzyme, suggest that it is very similar to the quinate-inducible 3-dehydroquinase found in Neurospora crassa and Aspergillus nidulans. This similarity was confirmed by direct N-terminal sequencing. PMID- 2306210 TI - Thyroid-hormone control of state-3 respiration in isolated rat liver mitochondria. AB - Oxidative phosphorylation can be treated as two groups of reactions; those that generate protonmotive force (dicarboxylate carrier, succinate dehydrogenase and the respiratory chain) and those that consume protonmotive force (adenine nucleotide and phosphate carriers. ATP synthase and proton leak). Mitochondria from hypothyroid rats have lower rates of respiration in the presence of ADP (state 3) than euthyroid controls. We show that the kinetics of the protonmotive force generators are unchanged in mitochondria from hypothyroid animals, but the kinetics of the protonmotive-force consumers are altered, supporting proposals that the important effects of thyroid hormone on state 3 are on the ATP synthase or the adenine nucleotide translocator. PMID- 2306213 TI - Unique molecular species of phosphatidylcholine containing very-long-chain (C24 C38) polyenoic fatty acids in rat brain. AB - Rat brain has been shown to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even carbon chain lengths from 24 to 38. These fatty acids are almost exclusively located in unusual molecular species of phosphatidylcholine at the sn-1 position of the glycerol backbone, whereas saturated, monoenoic and polyenoic fatty acids with less than 24 carbon atoms are present at the sn-2 position. Polyenoic VLCFA phosphatidylcholine in neonatal rat brain is enriched with n-6 pentaenoic and n-3 hexaenoic VLCFA with up to 36 carbon atoms, whereas the corresponding phospholipid in adult rat brain mainly contains n-6 tetraenoic and n-3 pentaenoic VLCFA with up to 38 carbon atoms. The total amount of polyenoic VLCFA associated with phosphatidylcholine is highest in the brain of immature animals. Polyenoic VLCFA phosphatidylcholine appears to be predominantly confined to nervous tissue in rats, and it is envisaged that this phospholipid is of physiological significance. PMID- 2306212 TI - Stimulated cholesterol-enriched platelets display increased cytosolic Ca2+ and phospholipase A activity independent of changes in inositol trisphosphates and agonist/receptor binding. AB - To investigate the mechanism of enhanced responsiveness of cholesterol-enriched human platelets, we compared stimulation by surface-membrane-receptor (thrombin) and post-receptor (AlF4-) G-protein-directed pathways. Platelets were labelled with [32P]Pi and [methyl-3H] choline chloride, incubated with sonicated lipid dispersions of various ratios of cholesterol and phospholipid, and loaded with the fluorescent Ca2+ indicator fura-2. We report the following. (1) Cholesterol enrichment enhances cytosolic Ca2+ accumulation and phospholipase A activation in response to both receptor-directed and post-receptor-directed agonists. No enhancement by cholesterol of phospholipase A activity at fixed Ca2+ concentrations is observed in lysed platelets, implying that no perturbation by cholesterol of phospholipase A/substrate interaction occurs in our preparations. (2) In both normal and cholesterol-enriched platelets, Ca2+ mobilization is promoted by a factor(s) apart from InsP3 that appear(s) to be modulated by cholesterol. A disproportionate increase in cytosolic Ca2+ relative to [32P]InsP3 is observed with increasing doses of thrombin in normal, and to a larger extent in cholesterol-enriched, platelets. When AlF4- is the agonist, there is no cholesterol-associated enhancement in [32P]InsP3 to account for the heightened Ca2+ rise seen with cholesterol enrichment. (3) Enhanced phospholipase A activation is not necessarily proportional to cytosolic Ca2+ increase. The magnitude of the increase in phospholipase A activity for a given rise in cytosolic Ca2+ is greater in cholesterol-enriched platelets that are stimulated by AlF4- than in those stimulated by thrombin. We conclude that increased membrane microviscosity associated with cholesterol enrichment may promote G protein/phospholipase A interaction as well as the Ca2(+)-release mechanism, without significantly altering G-protein/phospholipase C interaction. PMID- 2306215 TI - Fusion of phospholipid vesicles produced by the anti-tumour protein alpha-sarcin. AB - The anti-tumour protein alpha-sarcin causes fusion of bilayers of phospholipid vesicles at neutral pH. This is demonstrated by measuring the decrease in the efficiency of the fluorescence energy transfer between N-(7-nitro-2-1,3 benzoxadiazol-4-yl)-dimyristoylphosphatidylethano lamine (NDB-PE) (donor) and N (lissamine rhodamine B sulphonyl)-diacylphosphatidylethanolamine (Rh-PE) (acceptor) incorporated in dimyristoylphosphatidylcholine (DMPG) vesicles. The effect of alpha-sarcin is a maximum at 0.15 M ionic strength and is abolished at basic pH. alpha-Sarcin promotes fusion between 1,6-diphenylhexa-1,3,5-triene (DPH)-labelled DMPG and dipalmitoyl-PG (DPPG) vesicles, resulting in a single thermotropic transition for the population of fused phospholipid vesicles. Bilayers composed of DMPC and DMPG, at different molar ratios in the range 1:1 to 1:10 PC/PG, are also fused by alpha-sarcin. Freeze-fracture electron micrographs corroborate the occurrence of fusion induced by the protein. alpha-Sarcin also modifies the permeability of the bilayers, causing the leakage of calcein in dye trapped PG vesicles. All of the observed effects reach saturation at a 50:1 phospholipid/protein molar ratio, which is coincident with the binding stoichiometry previously described. PMID- 2306214 TI - Reduction in the level of intracellular myo-inositol in cultured soybean (Glycine max) cells inhibits cell division. AB - Although myo-inositol is included in media for the successful growth of plant tissues, the actual requirement of most tissues, including soybean (Glycine max) callus in suspension culture, for myo-inositol has not been demonstrated. We have made use of deoxyglucose to reduce intracellular levels of myo-inositol. Deoxyglucose is phosphorylated to deoxyglucose 6-phosphate, which inhibits L-myo inositol 1-phosphate synthase, an important enzyme in the synthesis of myo inositol. Addition of deoxyglucose to the medium resulted in a decrease in the intracellular level of myo-inositol that corresponded with a decrease in cell division. Cell viability was not affected. When myo-inositol was added to cells along with deoxyglucose, cell division was restored, as were intracellular levels of myo-inositol. Addition of myo-inositol had no affect on the uptake or metabolism of deoxyglucose. From these results we propose that myo-inositol has a role in maintaining cell division in soybean callus tissue in suspension culture. PMID- 2306216 TI - Use of a genetic variant to study the hexose transport properties of human skin fibroblasts. AB - Human skin fibroblasts from 'normal' subjects were found to possess at least two hexose transport systems. One system was responsible for the uptake of 2-deoxy-D glucose (dGlc), D-glucose and D-galactose, whereas the other was responsible primarily for the uptake of 3-O-methyl-D-glucose (MeGlc). The transport of dGlc was the rate-limiting step in the uptake process; over 97% of the internalized dGlc was phosphorylated and the specific activity of hexokinase was several times higher than that for dGlc transport. The dGlc transport system was activated by glucose starvation, and was very sensitive to inhibition by cytochalasin B and energy uncouplers. Fibroblasts isolated from a patient with symptoms of hypoglycaemia were found to differ from their normal counterparts in the dGlc transport system. They exhibited a much higher transport affinity for dGlc, D glucose and D-galactose, with no change in the respective transport capacity. Transport was not the rate-limiting step in dGlc uptake by these cells. Moreover, the patient's dGlc transport system was no longer sensitive to inhibition by cytochalasin B and energy uncouplers. This suggested that the intrinsic properties of the patient's dGlc transport system were altered. It should be noted that the patient's dGlc transport system could still be activated by glucose starvation. Despite the changes in the dGlc transport system, the MeGlc transport system in the patient's fibroblasts remained unaltered. The observed difference in the properties of the two hexose transport systems in the 'normal' and the patient's fibroblasts strongly suggests that the two transport systems may be coded or regulated by different genes. The present finding provides the first genetic evidence from naturally occurring fibroblasts indicating the presence of two different hexose transport systems. PMID- 2306218 TI - Comparison of the binding affinities of acyl-CoA-binding protein and fatty-acid binding protein for long-chain acyl-CoA esters. AB - Bovine and rat liver acyl-CoA-binding proteins (ACBP) were found to exhibit a much higher affinity for long-chain acyl-CoA esters than both bovine hepatic and cardiac fatty-acid-binding proteins (hFABP and cFABP respectively). In the Lipidex 1000- as well as the liposome-binding assay, bovine and rat hepatic ACBP effectively bound long-chain acyl-CoA ester, h- and c-FABP were, under identical conditions, unable to bind significant amounts of long-chain acyl-CoA esters. When FABP, ACBP and [1-14C]hexadecanoyl-CoA were mixed, hexadecanoyl-CoA could be shown to be bound to ACBP only. The experimental results give strong evidence that ACBP, and not FABP, is the predominant carrier of acyl-CoA in liver. PMID- 2306217 TI - Topography of the combining region of a Thomsen-Friedenreich-antigen-specific lectin jacalin (Artocarpus integrifolia agglutinin). A thermodynamic and circular dichroism spectroscopic study. AB - Thermodynamic analysis of carbohydrate binding by Artocarpus integrifolia (jackfruit) agglutinin (jacalin) shows that, among monosaccharides, Me alpha GalNAc (methyl-alpha-N-acetylgalactosamine) is the strongest binding ligand. Despite its strong affinity for Me alpha GalNAc and Me alpha Gal, the lectin binds very poorly when Gal and GalNAc are in alpha-linkage with other sugars such as in A- and B-blood-group trisaccharides, Gal alpha 1-3Gal and Gal alpha 1-4Gal. These binding properties are explained by considering the thermodynamic parameters in conjunction with the minimum energy conformations of these sugars. It binds to Gal beta 1-3GalNAc alpha Me with 2800-fold stronger affinity over Gal beta 1-3GalNAc beta Me. It does not bind to asialo-GM1 (monosialoganglioside) oligosaccharide. Moreover, it binds to Gal beta 1-3GalNAc alpha Ser, the authentic T (Thomsen-Friedenreich)-antigen, with about 2.5-fold greater affinity as compared with Gal beta 1-3GalNAc. Asialoglycophorin A was found to be about 169,333 times stronger an inhibitor than Gal beta 1-3GalNAc. The present study thus reveals the exquisite specificity of A. integrifolia lectin for the T antigen. Appreciable binding of disaccharides Glc beta 1-3GalNAc and GlcNAc beta 1-3Gal and the very poor binding of beta-linked disaccharides, which instead of Gal and GalNAc contain other sugars at the reducing end, underscore the important contribution made by Gal and GalNAc at the reducing end for recognition by the lectin. The ligand-structure-dependent alterations of the c.d. spectrum in the tertiary structural region of the protein allows the placement of various sugar units in the combining region of the lectin. These studies suggest that the primary subsite (subsite A) can accommodate only Gal or GalNAc or alpha-linked Gal or GalNAc, whereas the secondary subsite (subsite B) can associate either with GalNAc beta Me or Gal beta Me. Considering these factors a likely arrangement for various disaccharides in the binding site of the lectin is proposed. Its exquisite specificity for the authentic T-antigen, Gal beta 1 3GalNAc alpha Ser, together with its virtual non-binding to A- and B-blood-group antigens, Gal beta 1-3GalNAc beta Me and asialo-GM1 should make A. integrifolia lectin a valuable probe for monitoring the expression of T-antigen on cell surfaces. PMID- 2306219 TI - Hepatitis B surface antigen. Role of lipids in maintaining the structural and antigenic properties of protein components. AB - Most of the lipid components of hepatitis B surface antigen (HBsAg) can be removed by treatment with the non-ionic non-denaturing detergent beta-D-octyl glucoside (OG) followed by centrifugation through caesium chloride linear density gradients (density 1.15-1.32 g/ml). The conformational changes induced by the elimination of lipids decreased the helical content of HBsAg proteins from 52 to 28% as indicated by c.d. techniques. Measurements of the extent of quenching of protein fluorescence by iodide showed that half of the tryptophan residues which are buried in the native structure of HBsAg particles are brought close to the surface of the molecule by such conformational changes. The antigenic activity, as measured by binding to polyclonal antibodies, was decreased upon removal of lipids. Moreover, the six different antigenic sites recognized by our panel of monoclonal antibodies decreased their capacity to bind to the corresponding antibody when lipids were removed. However, the extent of this decrease differed for the different antibodies. Thus the apparent dependence of antibody binding on the lipid content seemed to indicate a greater involvement of the lipid-protein interaction for some of the epitopes than for others. PMID- 2306220 TI - Inhibition and inactivation of NADH-cytochrome c reductase activity of bovine heart submitochondrial particles by the iron(III)-adriamycin complex. AB - The NADH-cytochrome c reductase activity of bovine heart submitochondrial particles was found to be slowly (half-time of 16 min) and progressively lost upon incubation with the Fe2(+)-adriamycin complex. In addition to this slow progressive inactivation seen on incubation, a reversible fast phase of inhibition was also seen. However, if EDTA was added to the incubation mixture within 15 s, the slow progressive loss in activity was largely preventable. Separate experiments indicated that EDTA removed about one-half of the iron from the Fe2(+)-adriamycin complex in about 40 s. These results indicated the requirement for iron for the inactivation process. Since the Vmax. for the fast phase of inhibition was decreased by the inhibitor, the inhibition pattern was similar to that seen for uncompetitive or mixed-type inhibition. The direct binding of both Fe3(+)-adriamycin and adriamycin to submitochondrial particles was also demonstrated, with the Fe3(+)-adriamycin complex binding 8 times more strongly than adriamycin. Thus binding of Fe3(+)-adriamycin to the enzyme or to the inner mitochondrial membrane with subsequent generation of oxy radicals in situ is a possible mechanism for the Fe3(+)-adriamycin-induced inactivation of respiratory enzyme activity. PMID- 2306222 TI - Transcriptional control of the alpha 1(I) collagen gene involves orientation- and position-specific intronic sequences. AB - The 3' half of the first intron of the human alpha 1(I) collagen gene interacts with the promoter to regulate transcription. We questioned whether this intronic sequence also exerted its effect when placed 5' to the promoter. In transient transfection assays using several cell lines, little or no stimulation of alpha 1(I)-driven chloroamphenicol acetyltransferase transcription was observed. We conclude that transcriptional control of the alpha 1(I) gene is dependent on a complex series of interactions that require both orientation and position specificity of the intronic segment. PMID- 2306221 TI - Phosphorylated dolichols in aging. AB - The age-associated changes in the levels and synthesis of dolichyl phosphate and dolichyl diphosphate derivatives were investigated in brain and liver of 057B1/NNia mice. The total chloroform/methanol (2:1, v/v)-extractable phosphorylated dolichols of brain increased from 1.01 micrograms/g at 3 months to 5.22 micrograms/g at 28 months of age. The long-chain dolichyl diphosphate oligosaccharide (Dol-PP-oligo) levels of brain increased from 0.82 microgram/g in 3 months to 2.8 micrograms/g in 28-month-old animals. However, in liver and in kidney, the levels of these components were unaffected by age. Incorporation of labelled glucose from UDP-glucose into dolichyl phosphate glucose and Dol-PP oligo in brain microsomes was unaffected by age, whereas, in liver microsomes, the rates of synthesis of both components increased by 50-150%. The increased rate of synthesis and lack of accumulation of Dol-PP-oligo in liver suggest an active utilization and/or catabolism of these glycoprotein precursors. The accumulation of Dol-PP-oligo in aging brain may reflect its decreased utilization for N-glycosylation and/or reduced catabolism. PMID- 2306223 TI - Identification of the subunits of bovine NADH dehydrogenase which are encoded by the mitochondrial genome. AB - Products of the mitochondrial genome were identified in the bovine kidney cell line NBL-1 by labelling with [35S]methionine in the presence of cycloheximide. Seven proteins were precipitated by an antiserum to bovine heart NADH dehydrogenase, corresponding to the seven mitochondrial gene products identified in the human HeLa cell line. Comparison of these mitochondrial gene products with purified bovine NADH dehydrogenase by SDS/gel electrophoresis revealed that the ND-5 product is probably a previously unidentified protein of apparent Mr 51,000, and the ND-4 product is the protein of apparent Mr 39,000. PMID- 2306225 TI - Intermediary metabolism in the Swarm rat chondrosarcoma chondrocyte. AB - The rat chondrosarcoma chondrocyte has the dual capacity to metabolize glucose (mainly via glycolysis) and glutamine (via an oxidative pathway). Glutamine metabolism, unlike that of glucose, is unable to sustain intracellular ATP concentrations. Glutamine consumption by the chondrosarcoma chondrocyte, however, is significantly in excess of its utilization as an amide-group donor in hexosamine synthesis, implying a novel and major role in cell metabolism. PMID- 2306224 TI - Inositol is a constituent of detergent-solubilized immunoaffinity-purified rat liver 5'-nucleotidase. AB - myo-Inositol analysis of detergent-solubilized immunoaffinity-purified rat liver 5'-nucleotidase showed the presence of 1 mol of myo-inositol/mol of enzyme monomer. This provides unequivocal evidence that the ectoenzyme 5'-nucleotidase is attached to liver membranes by a glycosyl-phosphatidylinositol lipid anchor. PMID- 2306226 TI - Rapid kinetics of agonist-evoked changes in cytosolic free Ca2+ concentration in fura-2-loaded human neutrophils. AB - The initial kinetics of agonist-evoked rises in the cytosolic Ca2+ concentration [Ca2+]i were investigated in fura-2-loaded human neutrophils by stopped-flow fluorimetry. The rises in [Ca2+]i evoked by chemotactic peptide (fMet-Leu-Phe), platelet-activating factor and ADP all lagged behind agonist addition by 1-1.3 s. Lag times were not significantly different in the presence and in the absence of external Ca2+. Stimulation of the cells in the presence of extracellular Mn2+ resulted in a quench of fluorescence with a similar lag time to [Ca2+]i rise. The delay in onset of the rise in [Ca2+]i evoked by fMet-Leu-Phe was dependent on concentration, becoming longer at lower concentrations of agonist. These results indicate that both the agonist-evoked discharge of the intracellular Ca2+ stores and the generation of bivalent-cation influx lag behind agonist-receptor binding in neutrophils. Both pathways thus appear to be mediated by indirect mechanisms, rather than by a directly coupled process such as a receptor-operated channel. The temporal coincidence of the onset of store discharge with the commencement of bivalent-cation influx suggests that the two events may be causally linked. PMID- 2306227 TI - Alternative ligands as probes for the carotenoid-binding site of lobster carapace crustacyanin. AB - The apoproteins of the lobster carotenoprotein, crustacyanin, show single high affinity binding sites for the hydrophobic fluorescence probes 8-anilo-1 naphthalenesulphonic acid and cis-parinaric acid, and exhibit fluorescence transfer from tryptophan to the ligands. These results, together with information from the amino acid sequences, infer that the native carotenoid, astaxanthin, is bound to each apoprotein within an internal hydrophobic pocket, or calyx. PMID- 2306228 TI - Characterization of a cDNA clone encoding a new species of the nonspecific cross reacting antigen (NCA), a member of the CEA gene family. AB - To clarify the molecular structures of the nonspecific cross-reacting antigens (NCAs) produced by human granulocytes, we cloned cDNAs from libraries of normal white blood cells. A clone, NCA-W272, was found to code a protein similar to NCA of tumor cells. The protein consisted of a signal peptide (34 aa), domain-N (108 aa), -A1 (92 aa), -B1 (86 aa) and -M (29 aa). Similarity of the amino acid sequence of each domain to that of the tumor NCA was 72, 92, 76 and 79%, respectively. COS-1 cells transfected with an expression vector carrying the cDNA synthesized a 70 kDa glycoprotein, which was reactive with anti-NCA antibody and released from cell surface by phosphatidylinositol-specific phospholipase C. Thus the clone NCA-W272 was indicated to encode a new species of NCA distinct from the tumor NCA. PMID- 2306229 TI - Characterization of immunoreactive brain natriuretic peptide in human cardiac atrium. AB - Based on cDNA sequence data for human brain natriuretic peptide (BNP) precursor (1), a radioimmunoassay (RIA) system highly specific to human BNP (hBNP) was developed and used to characterize immunoreactive (ir-) hBNP in cardiac atrium. Gel filtration of ir-hBNP in atrium indicated that ir-hBNP was mainly comprised of two molecular forms of 13-15K and 4K. In reverse phase high performance liquid chromatography (HPLC), the low molecular weight (MW) ir-hBNP emerged as a single peak at an elution time identical to that of synthetic hBNP-32. The high MW ir hBNP was also eluted as a single peak. On the other hand, tissue concentrations of ir-hBNP in cardiac atria were found to be 9.98-593.22 pmol/g in 13 specimens, being about 1/150 the concentration of ir-human atrial natriuretic peptide (hANP). These results demonstrate that hBNP is present as a peptide in human heart, suggesting that hBNP is secreted from heart and functions together with hANP as a hormone. PMID- 2306230 TI - Parathyroid hormone-related protein is a possible autocrine growth inhibitor for lymphocytes. AB - Adult T-cell leukemia (ATL)-related cells have the ability to produce a newly isolated calcium-regulating protein, parathyroid hormone-related protein (PTHrP). The present study revealed that lectin-stimulated normal lymphocytes produce immunoreactive (IR)-PTHrP. When the T-cell-enriched fraction was purified from normal lymphocytes and then treated with lectin, a similar amount of IR-PTHrP was detected, suggesting that IR-PTHrP is an actual product of T-lymphocytes. A biologically active fragment of PTHrP, PTHrP(1-34), suppressed DNA synthesis in lectin-stimulated lymphocytes at concentrations greater than 50 pg/mL; the same concentration range of IR-PTHrP detected in the cultured media of lectin stimulated lymphocytes. Therefore, it is reasonable to postulate that PTHrP is a cytokine inhibiting the cellular growth of normal lymphocytes. PMID- 2306231 TI - Inhibition by serum components of the expression of lipoprotein lipase gene upon stimulation by growth hormone. AB - Growth hormone regulates in a positive way the expression of the lipoprotein lipase gene at a transcriptional level in preadipocyte Ob1771 cells. Inhibition by serum components of this expression was investigated upon stimulation by growth hormone. Low-molecular weight, lipid-soluble components (a serum lipid extract, corticosteroids and oleic acid) and high-molecular weight, hydrophilic components (TGF-beta and those present in delipidated serum) were inhibitory. Inhibition of the expression of LPL mRNAs and that of LPL activity were parallel. It is concluded that the regulation of the expression of LPL gene occurs likely at a transcriptional level and that a balance between multiple effectors present in serum are active in an opposite manner. PMID- 2306232 TI - Cytosolic-nuclear tumor promoter-specific binding protein (CN-TPBP) in human promyelocytic leukemia cells HL-60. AB - 12-O-Tetradecanoylphorbol 13-acetate (TPA) is a potent tumor promoter and is known to induce terminal differentiation of human promyelocytic leukemia cells HL 60 to mature monocytes. To investigate the molecular mechanism of TPA actions, TPA-specific binding proteins in HL-60 were analyzed. Anion exchange high performance liquid chromatography revealed that HL-60 cells possess TPA-specific binding proteins other than protein kinase C (PKC). One of these TPA-specific binding proteins exists in the cytosolic fraction of HL-60 cells, but translocates into the nuclear fraction of HL-60 cells after the treatment of the cells with TPA. The results suggest that HL-60 cells take up TPA into the nuclei via the TPA-specific binding protein. The TPA-specific binding protein binds TPA, phorbol 12,13-di-butylate, teleocidin B-2, teleocidin B-3, and debromoaplysiatoxin in a mutually competitive manner. However, the protein does not bind to okadaic acid, olivoretin C, retinoic acid, or dioxin. This cytosolic nuclear tumor promoter-specific binding protein (CN-TPBP) might play an essential role in the action of tumor promoters. PMID- 2306233 TI - The HIV protein, GP120, activates nuclear protein kinase C in nuclei from lymphocytes and brain. AB - Nuclear pool(s) of protein kinase C (PKC) may be a common target for hormones and growth factors which affect the trophic state of cells. The data presented demonstrate a time and dose-dependent activation of nuclear PKC by the HIV coat protein, gp120, in isolated nuclei from rat spleen and hippocampus. This gp120 stimulated PKC response was blocked by specific PKC inhibitors, a monoclonal antibody to PKC, and a monoclonal antibody directed against the murine T4 analog, L3T4. It is suggested that the gp120 interaction with the nuclear trophic factor PKC system may impair normal gene expression, and thus result in the clinical symptoms associated in AIDS infection. PMID- 2306235 TI - Iron-regulated outer membrane proteins in the periodontopathic bacterium, Bacteroides gingivalis. AB - Hemin has been implicated in the pathogenesis of the oral pathogen, Bacteroides gingivalis. In order to elucidate the role of hemin (iron) in the growth and expression of outer membrane proteins, B. gingivalis strain W50 was grown with and without hemin to induce iron-limitation. Cells grew slower under iron stress and growth was completely inhibited in the absence of added hemin. The outer membrane protein profiles of B. gingivalis grown under iron-replete and iron restricted conditions were studied by extrinsic radiolabelling with [125I] and polyacrylamide gel-electrophoresis. The induction of 10 surface proteins, with apparent molecular weights of 26, 29, 50, 56, 58, 60, 62, 71, 77, and 80 Kd, was observed in B. gingivalis grown under iron-restricted conditions. These proteins were repressed under iron-replete conditions. We postulate the involvement of the iron-regulated proteins in hemin uptake and virulence in B. gingivalis. PMID- 2306234 TI - Linear contour length dependence of electrical polarizability of nucleosomal DNA fragments: implications for the flexibility of DNA. AB - The transient electric birefringence of monodisperse oligonucleosomal DNA ranging from 145 to 990 base pairs has been studied. The orientation of fragments can be described in terms of an induced dipole moment with a small contribution of a permanent dipole. The electrical polarizability delta alpha was found to increase linearly with the DNA contour length. This unexpected dependence might result from a bent structure of DNA already considerable for very short segments. The observed delta alpha values agree with a segmental orientation of rigid subunits of length 13-18 nm as estimated in the elastic model of DNA with a kink angle of about 41 degrees. PMID- 2306236 TI - Regioselectivity and stereoselectivity in the metabolism of HMG-CoA reductase inhibitors. AB - Biotransformation of three analogs of simvastatin, L-672,201, L-157,012 and L 672,220, by rat liver microsomes has been examined. These compounds differ from each other at the 6' position of the hexahydronaphthalene system. When 6' substituents were in the alpha configuration, rat liver microsomes catalysed biotransformation primarily at the 6' position. Hydroxylation was stereoselective giving 6' beta-hydroxy derivatives as major metabolites. In contrast, when the 6' substituent had a beta-configuration, metabolism at this site was blocked. Rates of metabolism (nmols/mg protein/min) also indicated that 6' beta-derivatives were poorer substrates than their 6' alpha-counterparts. The results indicate that cytochrome P-450 exhibits a high degree of regio- and stereoselectivity in the metabolism of HMG-CoA reductase inhibitors. PMID- 2306237 TI - Somatostatin analog (SMS 201-995) inhibits the basal and angiotensin II stimulated 3H-thymidine uptake by rat adrenal glands. AB - The effects of a long-acting somatostatin analog SMS 201-995 injections on the basal and angiotensin II-stimulated [3H]-thymidine uptake by the rat adrenal glands incubated in vitro were examined. It was shown that SMS 201-995 significantly inhibited the [3H]-thymidine uptake and, additionally, suppressed the stimulatory effect of a single angiotensin II injection. PMID- 2306238 TI - Acidic and basic fibroblast growth factor mRNAs are expressed by skeletal muscle satellite cells. AB - We postulated that Fibroblast Growth Factor (FGF) involved in fetal or regenerative morphogenesis of skeletal muscle originated from this tissue. Using a bovine retina cDNA probe encoding acidic FGF, we showed that growing muscles from bovine fetuses express this mRNA, but that this expression is reduced in neonate muscles. Cultures of proliferating satellite cells isolated from adult rat muscles expressed aFGF mRNA strongly but bFGF mRNA weakly; these mRNAs disappeared in cells differentiated into myotubes. 10(-7)M 12-O-tetradecanoyl phorbol -13-acetate (TPA) increased aFGF mRNA expression in both proliferating and differentiated satellite cells. Contrastingly, proliferating L6 myogenic cells only expressed aFGF mRNA significantly under TPA treatment. Therefore, the satellite cells did seem to be a possible source for FGF, especially aFGF, which might regulate the myogenic process. PMID- 2306239 TI - Preparation and characterization of polyclonal and monoclonal antibodies against the insecticide DDT. AB - A synthetic DDT derivative in which the molecular structure of DDT was completely retained was coupled to bovine serum albumin. Animals were immunized with the DDT bovine serum albumin conjugate and polyclonal and monoclonal antibodies against the insecticide were isolated. These antibodies seemed to be the first true anti DDT antibodies and distinguished much better between DDT and DDT metabolites than previously prepared anti-DDT antisera. In competitive solid phase radioimmunoassays, DDT concentrations as low as 10 nM or 0.0035 mg/1 were detectable. The anti-DDT antibodies can be used for environmental analyses and lend themselves to the elucidation of the structure of the DDT binding site. PMID- 2306240 TI - Purification of a novel eIF-2 alpha protein kinase from calf brain. AB - A new eukaryotic initiation factor 2 kinase has been purified for the first time from calf brain cytosol. The purification of a nonabundant novel protein kinase activity, designated as PKI, that phosphorylates the alpha subunit of eukaryotic initiation factor 2 is described. The protein kinase activity was assayed using purified initiation factor 2 as a substrate and was purified by ammonium sulphate precipitation, conventional chromatography in heparin-Sepharose and phosphocellulose and by high performance size exclusion and anion exchange chromatographies. The protein kinase activity elutes in the region of 140,000 in the size exclusion chromatography and is associated with two different polypeptides a and b, with relative molecular masses of 38,000 and 20,000 and an approximate ratio of 2.5-3.0:1. The protein kinase does not phosphorylate casein or histones and it is independent of cyclic nucleotides. It can be classified as a serine kinase since the phosphorylation of the alpha subunit of eIF-2 is produced in serine residues. Under these conditions none of the kinase subunits are phosphorylated. PMID- 2306241 TI - Thyroid peroxidase gene promoter confers TSH responsiveness to heterologous reporter genes in transfection experiments. AB - The cyclic AMP-mediated transcriptional regulation of the enzyme thyroperoxidase by thyrotropin (TSH) in thyroid follicular cells was examined at the molecular level. The 5' end of the human thyroperoxidase gene was isolated and sequenced and the transcription start site was mapped by S1 nuclease analysis. A 0.9 kilobase pair DNA fragment of the promoter was shown to confer responsiveness to thyrotropin, and cyclic AMP, in transient expression assays using two different reporter genes. Several potential sites for specific interaction with nuclear transcription factors which could be involved in the regulation of thyroperoxidase gene transcription were identified. PMID- 2306242 TI - Expression of human pregnancy specific beta 1 glycoprotein (PSG) genes during placental development. AB - Using gene-specific oligonucleotide probes, the expression of four pregnancy specific beta 1 glycoprotein (PSG) genes termed A, B, C-D and E (Streydio et al., 1988 and in press) and of some of their splice variants Ci, C and D were analysed during human placental development. Except for a stronger hybridization signal obtained at 9 weeks of gestation, which might be correlated to the development of the placenta, the relative amounts of the different PSG mRNAs showed little variation throughout pregnancy as revealed by Northern blots performed at 6, 13, 18 and 40 weeks of gestation. The expression of the different PSG genes does not seem to be developmentally regulated, in contrast to placental lactogen, used as a control, the expression of which is clearly correlated with the age of gestation. PSG D, A, E transcripts seem equally abundant, while PSG B expression was much lower. Moreover, the proportion of the PSG C-D variants resulting from alternative splicing remained constant during gestation. PMID- 2306243 TI - The effect of sulfhydryl blocking groups on the thermal unfolding of alpha alpha tropomyosin coiled coils. AB - Equilibrium thermal unfolding curves from circular dichroism are given for alpha alpha tropomyosin and for alpha alpha tropomyosin blocked at C190 by a) carboxyamidomethylation; b) carboxymethylation. Although commonly assumed to be benign, these blocks in fact produce some weakening. All three substances are virtually completely alpha-helical at low T. Fraction helix vs T for parent protein is apparently monophasic (single inflection point). The curve for carboxyamidomethylated protein is very close to that of the parent, but is biphasic, with a small "pretransition". The curve for carboxymethylated protein is prominently biphasic, with a much larger pretransition. Some implications for the molecular model of these equilibria are discussed. PMID- 2306244 TI - Hepatic microsomal oxygenation of aldehydes to carboxylic acids. AB - Hepatic microsomal oxygenation of aldehydes to carboxylic acids was investigated. Aldehydes (veratrum aldehyde, cinnamic aldehyde, myrtenal, cuminaldehyde, 3 phenylpropionaldehyde, perillaldehyde and 9-anthraldehyde) were incubated with hepatic microsomes of mice in the presence of an NADPH-generating system under 18O2 (97 atom%). The incorporation of oxygen-18 into carboxylic acids formed was determined by gas chromatography-mass spectrometry. Oxygen-18 was incorporated into the carboxylic acids formed from all aldehyde substrates examined. Hepatic microsomal formation of 3,4-dimethoxybenzoic acid and cumic acid from veratrum aldehyde and cuminaldehyde, respectively, was inhibited by CO and SKF 525-A. These results indicate that the oxygenation of aldehydes which may be catalyzed by cytochrome P450 is a common reaction in the biotransformation of xenobiotic aldehydes. PMID- 2306245 TI - TPA stimulates S6 phosphorylation but not protein synthesis in Ehrlich cells. AB - Increased phosphorylation of ribosomal protein S6 has been extensively correlated with an increased rate of protein synthesis. We report here that under two separate conditions in Ehrlich cells an increase in the level of S6 phosphorylation does not result in any increase in the rate of protein synthesis. 1) In glutamine-deprived cells TPA stimulates S6 phosphorylation but has no effect on the rate of protein synthesis, 2) In cells deprived of serum growth factors, addition of serum stimulates both S6 phosphorylation and protein synthesis while TPA stimulates only S6 phosphorylation. These results show that increased phosphorylation of S6 is not sufficient to cause increased rates of protein synthesis, and suggest that additional factors may play a more direct role. PMID- 2306246 TI - Na(+)-dependent Ca2+ efflux inhibits stimulus-induced secretion in bovine chromaffin cells. AB - Stimulations of chromaffin cells with histamine and ionomycin produced rises in cellular free Ca2+ level. The removal of Na+ ions from the medium prolongated the rises without changing the magnitude. The stimulations also facilitated 45Ca2+ efflux from cells by over 3-fold. The facilitation was, however, largely abolished by the Na+ removal, indicating the Na(+)-dependent efflux is a major system to expel Ca2+ from the stimulated cells. The Na+ removal also enhanced secretions evoked by these stimuli. The results suggest the Na(+)-dependent Ca2+ efflux by lowering the elevated cellular Ca2+ plays a role in terminating the stimulus-induced secretion. PMID- 2306247 TI - The influence of pH on Ca2+ exchange in ferret heart mitochondria. AB - The effect of pH changes on Ca2+ transport by isolated heart mitochondria was measured. Two components of Ca2+ transport were identified, an accumulation dependent on mitochondrial respiration and a Na+-dependent efflux. A decrease of pH over the range 7.7-6.7 reduced the initial rate and the total amount of respiration dependent Ca2+ accumulation. At pH 7.2 the [Na+] required to activate half-maximal efflux, k1/2, was 7.5 +/- 1.1 mM. Decreasing the pH over the range 7.7 to 6.9 increased the k1/2 from 3.6 to 11.6. The effect of acidosis was more profound on the respiration dependent Ca2+ uptake than the Na+-dependent efflux. PMID- 2306248 TI - Drug resistance to cis-diamminedichloroplatinum (II) in Chinese hamster ovary cell lines transfected with glutathione S-transferase pi gene. AB - Establishment of Chinese hamster ovary (CHO) cell lines expressing human glutathione S-transferase-pi (GST-pi) was performed after cotransfection of pSV2 neo and human GST-pi cDNA-carrying plasmid p beta actGPi-2. About 30 G418 resistant clones were tested for their expression of GST-pi by Northern blot analysis. Two clones, beta 2-3 and beta 2-5, expressed a significant amount of GST-pi mRNA; and one clone, beta 1-1, that did not was also used for further study. Western blot analysis with anti-GST-pi antibody showed significant increases of GST-pi in beta 2-3 and beta 2-5, but not in beta 1-1. Northern blot analysis with the human GST-pi cDNA probe showed that the increase in the expression of GST-pi-mRNA in beta 2-3 and beta 2-5 was respectively 2- and 4-fold higher than that in beta 1-1. Southern blotting analysis showed that beta 1-1, beta 2-3 and beta 2-5 contained about one copy of the human GST-pi cDNA sequence. beta 2-3 and beta 2-5 were resistant to 1.4- and 3.0-fold higher doses of CDDP than CHO, respectively, but beta 1-1 was not. Increased expression of GST-pi might be associated with CDDP-resistance in CHO cells. PMID- 2306249 TI - Characterization of a reversible denaturational transition occurring in the case of an irreversibly denaturing membrane spanning protein. AB - During a previous investigation of the thermal denaturation of the membrane spanning domain of the human erythrocyte band 3 protein, a novel transition was noted. The most significant aspect of this transition is its reversibility, since both the endothermic and the functional denaturation of band 3 are clearly irreversible. In this report this reversible thermal transition, manifested by a change in the temperature course of the heat capacity at the protein thermodenaturation temperature, is characterized and briefly discussed. PMID- 2306250 TI - Cytochrome P-450-catalyzed formation of 20-hydroxy-ecdysone in larval housefly mitochondria. AB - Six forms of cytochrome P-450 in the mitochondria of larvae from Musca domestica were isolated by solubilization with CHAPS followed by ammonium sulfate fractionation and HPLC on an anion-exchange column. Forms 1, 2, 3, 5, and 6 catalyzed the formation of 20-hydroxy-ecdysone from ecdysone in the presence of NADPH and pig adrenal adrenodoxin and adrenodoxin reductase at rates not much different that observed in mitochondria; whereas, fraction 4 showed an activity which was about 10-fold higher than mitochondria. Forms 4 and 5 were further purified by HPLC on a cation-exchange column followed by removal of excess detergent by hydroxyl apatite column chromatography. In vitro reconstitution of the monooxygenase activity confirmed that form 4 is primarily involved in the formation of 20-hydroxy-ecdysone from ecdysone. SDS-polyacrylamide gel electrophoresis indicated a high degree of purity of both forms 4 and 5, with molecular weights of 56 and 58 KDa, respectively. PMID- 2306251 TI - Tyrosine phosphorylation of cytosolic proteins in human erythrocytes. AB - Some cytosolic proteins of human erythrocytes can be phosphorylated on tyrosine residues by endogenous Tyr-protein kinase(s). Their phosphorylation is enhanced by addition of Tyr-protein kinase, purified from human erythrocyte cytosol. The most phosphorylatable is a 19 kDa protein. Its phosphorylation is more activated by Mn2+ than by Mg2+. It is inhibited by NaC1, 2,3-bisphosphoglycerate and by heparin. Similar response to the above effectors is exhibited by the phosphorylation of the other protein bands. However, the phosphorylation of a 73 kDa double band, which is negligible in the absence of added NaC1, is stimulated by this salt. PMID- 2306252 TI - Amino acid sequence of ghilanten: anticoagulant-antimetastatic principle of the South American leech, Haementeria ghilianii. AB - This study reports the amino acid sequence of ghilanten, an anticoagulant antimetastatic principle of the hematophagous leech, Haementeria ghilianii. Ghilanten consists of 119 amino acids with twenty cysteines and a consensus sequence for heparin-binding at its carboxyl-terminus. Arginine-34 represents the reactive residue involved in the active-site inhibition of trypsin and Factor Xa. Immunoreactivity data suggest that heterogeneity among ghilantens is due in part to amino acid substitutions at their carboxyltermini. PMID- 2306253 TI - Defluorination of 1,1,1,2-tetrafluoroethane (R-134a) by rat hepatocytes. AB - As part of its toxicological evaluation we assessed the in vitro metabolism of 1,1,1,2-tetrafluoroethane (R-134a), a non-ozone-depleting chemical likely to replace dichlorodifluoromethane (R-12) as an air-conditioning refrigerant. Hepatocyte suspensions in sealed flasks produced increasing quantities of F- (detected in the liquid media) as the headspace concentration of R-134a increased from 1% to 50% (balance of atmosphere 95% O2-5% CO2); the kinetics of defluorination suggested substrate-saturation. Little F- was detected in cultures without R-134a or in cell suspensions heated prior to addition of R-134a. Halothane (1,1,1-trichloro-2-bromo-2-chloro-ethane), although not defluorinated by hepatocytes maintained with 95% O2, inhibited defluorination of R-134a. Hepatocytes from phenobarbital-treated rats dehalogenated high (greater than or equal to 25%) concentrations of R-134a at greater rates than cells from untreated rats. These findings are consistent with the hypothesis that oxidative metabolism of R-134a by cytochrome P-450 can occur in vivo. PMID- 2306254 TI - Inhibition of human beta-factor XIIa by squash family serine proteinase inhibitors. AB - Many inhibitors of trypsin and human beta-factor XIIa have been isolated from squash and related seeds and sequenced (Wieczorek et al., Biochem. Biophys. Res. Comm. (1985) 126, 646-652). The association equilibrium constants (Ka) of several of these inhibitors have now been determined with human beta-factor XIIa using a modification of the method of Green and Work (Park et al., Fed. Proc. Fed. Am. Soc. Exp. Biol. (1984) 43, 1962). The Ka's range from 7.8 x 10(4) M-1 to 3.3 x 10(8) M-1. Two isoinhibitors from Cucurbita maxima seeds, CMTI-I and CMTI-III, differ in only a single glutamate to lysine change in the P'4 position. This results in a factor of 62 increase in the Ka of the lysine inhibitor, CMTI-III (Ka = 3.3 x 10(8) M-1). To our knowledge, this is the largest effect ever seen for a residue substitution at the P'4 position of a serine proteinase inhibitor. The result is even more surprising because beta-factor XIIa's natural substrate, Factor XI, contains Gly in the P'4 position. PMID- 2306255 TI - Trifluoperazine inhibition of contraction in permeabilized skeletal, cardiac and smooth muscles. AB - To gain insights into the mechanism of the central helix of calmodulin and troponin-C in the Ca2(+)-regulation of force development in striated and smooth muscles, the present study was made of the TFP induced inhibition of contraction, and of the uptake of these proteins by skinned fibers. Calmodulin was four-fold more sensitive to TFP than TnC, but the inhibition was found to be identical for skeletal and cardiac muscles despite the differences in their troponin-C isoforms. Also, the results were comparable between fast-twitch fiber, when calmodulin was exchanged for troponin-C to act on TnI, and smooth muscle, where calmodulin acts on myosin light chain kinase. These findings indicate that the inhibition of force by TFP is entirely due to its binding to the hydrophobic sites in the central helix. The uptakes of troponin-C and calmodulin were also different, and this is explained by a TFP-independent domain in troponin-C that binds TnI. PMID- 2306256 TI - Unusual denaturation properties of vicilin from Cajanus cajan. AB - Pigeonpea (Cajanus cajan) vicilin (Mr 190 kD) holoprotein contains 2 subunits and the N-terminal amino acid sequence is Gly-Ala-Arg-Val-Asp-Gln-Glu for purified vicilin subunit 1 (Mr 72 kD) and Thr-Thr-Cys-Met-Glu-Ser-Gly for purified vicilin subunit 2 (Mr 57 kD). Circular dichroism spectra of vicilin indicate the occurrence of a predominant beta- pleated sheet structure. The fluorescence studies of vicilin reveal its unusual stability to 8 M urea and 6 M guanidine HCl. PMID- 2306257 TI - Specific inhibitory conformation of dipeptides for chymotrypsin. AB - Based on the analyzed conformation of a chymotrypsin inhibitor H-delta Phe-Phe OMe, we have designed a series of diastereomeric phenylalanylphenylalanine methyl esters and derivatives as possible inhibitors. Among the peptides synthesized, H D-Phe-L-Phe-OMe was found to be very resistant to chymotrypsin in spite of its L Phe-OMe structure at the C-terminus. It inhibited the enzyme fairly strongly and competitively with Ki = 9.0 x 10(-5) M in the assay using Ac-Tyr-OEt as a substrate. The measurements of the NOEs in high-resolution 1H-NMR analyses indicated the presence of the hydrophobic core built by the intramolecular interaction between the D-Phe-phenyl and ester-methyl groups. It was suggested that this core interacts with the chymotrypsin S2 site (Trp215) and Phe2 with the S1 site. The backbone structure of this dipeptide was assumed to be in an inhibitory conformation that fits the active center of the enzyme. PMID- 2306258 TI - Dual action of hydroxylated diphenylethylene estrogens on protein kinase C1. AB - Protein kinase C (PKC) I (gamma), II (beta) and III (alpha) subspecies are all activated by 1,1-di-(p-hydroxyphenyl)ethylene derivatives (DPE) at micromolar concentrations. This PKC activation depends on the presence of both Ca2+ and phosphatidylserine (PS) but does not require diacylglycerol (DG). DPEs enhance PKC activity at low PS concentrations, but not at saturating PS concentrations. Like DG, DPEs increase the apparent affinity of PKC for PS as well as for Ca2+, but lead to a decrease in the catalytic activity (Vmax). In the presence of saturating DG concentrations, DPEs exhibit an inhibitory action. The derivatives also inhibit the activity of the proteolytic fragment of PKC, protein kinase M. It is concluded that DPEs are mixed-type inhibitors, probably interacting with the catalytic domain of the enzyme. PMID- 2306259 TI - cDNA cloning of the hydroxysteroid sulfotransferase STa sharing a strong homology in amino acid sequence with the senescence marker protein SMP-2 in rat livers. AB - A cDNA encoding hydroxysteroid sulfotransferase a (STa), which catalyzes activation of carcinogenic polycyclic hydroxymethyl-arenes, was isolated from a lambda gtll cDNA expression library constructed from poly(A)+RNA of a female Sprague-Dawley (SD) rat liver. The cDNA, designated as ST-40, consisted of 1,015 base pairs which had an open reading frame of 852 base pairs encoding the entire rat STa subunit of 284 amino acids. The nucleotide base sequence of the ST-40 cDNA shared a strong homology of 94.4% with that of ST-20 cDNA encoding a hydroxysteroid ST which had been reported by us. The deduced amino acid sequence of STa had a homology of 73.7% with that of an SD rat liver senescence marker protein (SMP-2) consisting of 282 amino acid residues. However, STa was found to share a much stronger homology of 92% on the average with SMP-2 in their four specific regions corresponding to about 60% of the total sequences, indicating SMP-2 to be an isozyme of hydroxysteroid ST. PMID- 2306260 TI - Growth state dependent increase of glutathione by homocysteine and other thiols, and homocysteine formation in glutathione depleted mouse cell lines. AB - Homocysteine has been shown to increase glutathione levels in C3H/10T1/2 Cl 8 cells. The present paper confirms that this increase was specific for non dividing cells. Several other thiols and disulfides, including cysteamine, mercaptoethanol and dithioerythritol, also increased glutathione, but the specificity for quiescent non-dividing cells was confined to homocysteine only. Cysteamine was most efficient, increasing glutathione 5-fold in confluent, non dividing cells, and 3.2-fold in exponentially growing Cl 8 cells. The results indicate that the increase in glutathione was not specific for homocysteine or other cysteine generating agents, but rather related to the presence of potential thiol, either in free form, as thiolactone or in its oxidized, disulfide form. The effect of the glutathione synthesis inhibitor BSO was investigated in detail in both C3H/10T1/2 Cl 8 cells and in R1.1. mouse lymphoma cells. Twenty-four hours after addition of 20 microM BSO to exponential growing Cl 8 cells the glutathione content was reduced to 5.5%, with minimal toxic effect. To achieve the same GSH depleting effect on exponential growing R1.1. cells, the BSO concentration had to be increased to 50 microM, which had a slight, but distinct growth inhibitory effect on the lymphoma cells. Based on these data, the possibility that glutathione mediated homocysteine production was investigated in part by depleting the cells of glutathione and determining the homocysteine export rate as a measure of the intracellular production of the metabolite. The results showed that glutathione depletion by BSO had no effect on the homocysteine export rate in Cl 8 cells, while in R1.1. cells a moderate decrease in homocysteine export rate accompanied by a slight, but distinct decrease in growth rate, was observed when the cells were depleted of glutathione. In addition, these data indicate that BSO did not interfere with the overall transmethylation rate, and this observation supports the view of BSO as a specific inhibitor of GSH synthesis. A general difference between the homocysteine export rate in Cl 8 and R1.1. cells was observed. The former demonstrated a decreasing export rate during exponential growth, while the latter showed an initial decrease and then a slight increase in homocysteine export rate. PMID- 2306261 TI - High affinity phenacetin O-deethylase is catalysed specifically by cytochrome P450d (P450IA2) in the liver of the rat. AB - Phenacetin is metabolized primarily by O-deethylation to paracetamol (POD activity), a reaction catalysed by cytochrome P450. The high affinity component of POD activity is inducible in rat liver by treatment of the animals with polycyclic aromatic hydrocarbons. Following treatment with hydrocarbons such as 3 methylcholanthrene (MC) and isosafrole (ISF) both cytochromes P450c (P450IA1) and P450d (P450IA2) are also induced in rat liver. Studies with the reconstituted enzymes have shown that both forms of P450 catalyse phenacetin O-deethylation at rates that exceeded that of the high affinity component of activity of hepatic microsomal preparations from 3-methylcholanthrene-treated rats (at 4 microM phenacetin: P450c, 440 +/- 40 pmol/nmol/min; P450d, 1030 +/- 10 pmol/nmol/min; microsomal fraction, 163 pmol/mg/min). Specific inhibitory antibodies (both monoclonal and monospecific polyclonal) were used to define the specificity of microsomal POD activity. These studies have shown that hepatic high affinity POD activity is exclusively catalysed by cytochrome P450d in both untreated rats and in rats pretreated with MC. PMID- 2306263 TI - A monoclonal anti-imipramine antibody with antidepressant binding properties similar to the muscarinic receptor. AB - A murine monoclonal antibody raised using imipramine conjugated to bovine serum albumin bound free imipramine with high affinity (KD = 24 nM). The antibody had a binding affinity profile for tricyclic and other uptake-inhibitor type antidepressants which correlated highly with the affinities of the same compounds for the brain acetylcholine muscarinic receptor, but not for plasma-membrane 5 hydroxytryptamine carriers. This antibody was not similar in binding properties to polyclonal antisera produced using the same antigen but was highly similar in binding properties to a monoclonal anti-nortriptyline antibody, ANT3, raised by Marulo et al. (Marulo S, Hoebeke J, Guillet JG, Andre C and Strosberg AD, J Immunol 138: 524-526, 1987) using a different antigen. PMID- 2306262 TI - The inducibility and catalytic activity of cytochromes P450c (P450IA1) and P450d (P450IA2) in rat tissues. AB - The metabolism of phenacetin is primarily by cytochrome P450-dependent O deethylation to paracetamol (POD activity). In untreated rats, microsomal POD activity is detectable in both the liver and lung, but not in the small intestine or the kidney. POD activity is highly induced in both hepatic and extrahepatic tissues of the rat following treatment with polycyclic aromatic hydrocarbons such as 3-methylcholanthrene (MC). Only cytochrome P450c (P450IA1) is inducible in rat extrahepatic tissues by MC or isosafrole, whereas in the liver both cytochromes P450c and P450d (P450IA2) are inducible by these compounds. Specific antibodies to cytochromes P450c and P450d were used to study the expression and function of these two related isoenzymes in rat liver and extrahepatic tissues before and after induction with MC. Whereas cytochrome P450d is responsible for all of the high affinity POD activity in hepatic microsomal fractions of both untreated and MC treated rats, this activity is mediated only by P450c in microsomal fractions from extrahepatic tissues following MC treatment. POD activity of microsomal fractions from lung of untreated rats was not mediated by either cytochrome P450c or P450d. PMID- 2306264 TI - Effects of thiamine deficiency on hepatic cytochromes P450 and drug-metabolizing enzyme activities. AB - To elucidate the mechanisms by which thiamine deficiency affects hepatic microsomal monooxygenase activities, the effect of thiamine deficiency on two constitutive cytochrome P450 isozymes, P450IIE1 and P450IIC11, was investigated, using weanling male Sprague-Dawley rats. The clinical signs of thiamine deficiency were apparent after feeding a thiamine-deficient diet for 3 weeks. Thiamine deficiency caused an increase in P450IIE1, which was determined by N nitrosodimethylamine demethylase assay and immunoquantitation of P450IIE1. This increase in the P450IIE1 level was mainly attributed to thiamine deficiency per se but not to dietary restriction. Ketone bodies were not elevated in thiamine deficient rats, whereas ketone bodies were elevated and may have served as inducing factors in calorically restricted pair-fed animals. Injections of pyruvate or pyrithiamine in addition to thiamine deficiency did not potentiate the induction effect. On the other hand, thiamine deficiency did not affect the level of P450IIC11 during the 3 weeks of feeding the thiamine-deficient diet. In addition, thiamine deficiency increased cytosolic glutathione S-transferase activity but not steroid isomerase activity. The present study demonstrates the specificity of thiamine deficiency per se in the induction of P450IIE1 which does not involve an increase in the ketone body level. PMID- 2306265 TI - Effects of hepatic peroxisome proliferators and 12-O-tetradecanoyl phorbol-13 acetate on catalase and other enzyme activities of embryonic cells in vitro. AB - The effects of the hepatic peroxisome proliferators (HPPs) clofibrate, di-(2 ethylhexyl)-phthalate (DEHP), mono-(2-ethylhexyl)phthalate (MEHP) and 2,4 dichlorophenoxy acetic acid (2,4-D) on the activities of some peroxisome associated enzymes and marker enzymes for other organelles, have been studied in primary Syrian hamster embryo (SHE) cells and Wistar rat embryo (WRE) cells. The majority of the cells are fibroblast-like. 12-O-Tetradecanoyl phorbol-13-acetate (TPA) was included as it has been suggested that it may act as a peroxisome proliferator. The specific activities of catalase, fatty acyl-CoA oxidase (FAO) and peroxisomal beta-oxidation were approximately 100-fold lower in the embryonic cells than in rat hepatocytes. Other peroxisome-associated oxidases were not detected. The dihydroxyacetone-phosphate acyltransferase (DHAPAT) activity was comparable to that in rat liver. Marker enzymes for other organelles had specific activities comparable to rat hepatocytes. Catalase was shown by digitonin titration to be contained in a peroxisome-like compartment in both SHE and WRE cells. Clofibrate, DEHP and MEHP increased the catalase activity, which might suggest peroxisome proliferation. However, the findings that FAO and peroxisomal beta-oxidation did not increase or only very slightly, argue against peroxisome proliferation. 2,4-D and TPA induced no or only a very slight increase in the catalase activity. PMID- 2306266 TI - Release of [hydroxyproline3]-kinins by tissue kallikreins of pig, rat and man. AB - To determine the susceptibility of kininogens containing the recently described [Hyp3]-bradykinin moiety to cleavage by tissue kallikreins, we have studied the release of [Hyp3]-kinins from heat inactivated human plasma by purified tissue kallikreins. Kallikreins from man and pig were employed and compared with purified rat urinary kallikrein which is known to have a different cleavage specificity. Kinins released were separated by a modified reversed phase HPLC method and quantitated by bioassay and radioimmunoassay. Human urinary kallikrein and hog tissue kallikreins released 85-90% of the total kinins as Lys-bradykinin and 10-15% as [Hyp3]-Lys-bradykinin. In contrast, rat urinary kallikrein released 77% as bradykinin, 22% as [Hyp3]-bradykinin and negligible amounts of [Hyp3]-Lys bradykinin from the identical substrate source indicating that rat tissue kallikreins prefer the Lys-Arg-bond within both unhydroxylated and hydroxylated kininogens. Therefore, hydroxylation of human kininogens apparently does not affect their ability to serve as substrates for tissue kallikreins with different cleavage specificities. PMID- 2306267 TI - Non-steroidal anti-inflammatory drug-copper complex modulation of polymorphonuclear leukocyte migration. AB - These studies were intended to compare the effects of aspirin, 3,5 diisopropysalicylic acid (3,5-DIPS), and indomethacin with those of their copper complexes: Cu(II)2(aspirinate)4, Cu(II)2(3,5-DIPS)4, and Cu(II)2(indomethacinate)4 as well as Cu(II)2(acetate)4 on polymorphonuclear leukocyte (PMNL) random and directional migration, in addition to their anti inflammatory activities. Experiments were performed both in vivo and in vitro. In vitro modifications of PMNL migration were measured with the Boyden chamber using N-formyl-methionyl-leucyl-phenylalanine (fMLP) as the chemoattractant and in the agarose assay using fMLP and serum chemotactic derivatives of complement as chemoattractants. In vivo anti-inflammatory activities of these compounds were determined after induction of a serum-induced pleurisy in the rat, and measurement of exudate volume and number of exudative cells 4 hr later. Copper complexes of non-steroidal anti-inflammatory drugs (NSAIDs) were found to be more effective in decreasing random migration and chemotaxis of PMNLs than their parent drugs or Cu(II)2(acetate)4 in in vitro studies. Only chemotaxis was found to be reduced significantly for PMNLs obtained from pleuritic rats after in vivo treatment and the order of copper complex effectiveness was: Cu(II)2(indomethacinate)4 greater than Cu(II)2(3,5-DIPS)4 greater than Cu(II)2(aspirinate)4. All doses of Cu(II)2(acetate)4 administered in vivo failed to affect chemotactic activity. Copper complexes of NSAIDs were also more effective than their parent drugs as anti-inflammatory agents, and Cu(II)2(acetate)4 had no anti-inflammatory activity in this model of inflammation. The order of anti-inflammatory activity was: Cu(II)2(indomethacinate)4 greater than Cu(II)2(3,5-DIPS)4 greater than Cu(II)2(aspirinate)4. PMID- 2306268 TI - Inhibition of acyl coenzyme A: cholesterol acyl transferase by trimethylcyclohexanylmandelate (cyclandelate). AB - Cyclandelate was an effective inhibitor of rat hepatic acycloenzyme A: cholesterol acyltransferase (ACAT) with a concentration of 80 microM being required for half maximal inhibition. A similar effect was seen with human and rabbit liver microsomal enzymes. The drug did not compete with oleoyl CoA or cholesterol and could be removed from enzyme preparations by washing. It was hydrolysed rapidly by rat liver microsomes to products which were non inhibitory. No hydrolysis of the drug was seen with non hepatic microsomes and the concentration of cyclandelate required to cause half maximal inhibition of ACAT in the transformed mouse macrophage J774 microsomal fraction was less than 30 microM. The possible significance of the differential actions of cyclandelate towards hepatic and extra hepatic ACAT in vivo is discussed. PMID- 2306270 TI - Immunodetection with a monoclonal antibody of glutathione S-transferase mu in patients with and without carcinomas. AB - Several monoclonal antibodies against human liver glutathione S-transferase mu were developed. One of these monoclonal antibodies, called GST-3H4 was further characterized and used in this study. In hepatic tissue, after immunoblotting, GST-3H4 strains a 27 kDa protein with a pI value of 6.2. GST-3H4 recognizes other human class-mu glutathione S-transferases, but does not detect acidic or basic glutathione S-transferases. By immunodetection with this monoclonal antibody, glutathione S-transferase mu can be demonstrated in human breast, stomach, liver, small and large intestine, mononuclear blood cells, kidney and placenta. A 100% correlation is found in the distribution of glutathione S-transferase mu when different tissues or mononuclear blood cells from the same individuals are investigated. In 62.5% of the mononuclear blood cells from controls, glutathione S-transferase mu is present. In patients with polyposis coli, breast cancer or colon cancer a similar distribution is found. Therefore no important role for glutathione S-transferase mu deficiencies in the aetiology of these diseases is suggested. PMID- 2306269 TI - Potentiation of the cell specific toxicity of paraquat by 1,3-bis(2-chloroethyl) 1-nitrosourea (BCNU). Implications for the heterogeneous distribution of glutathione (GSH) in rat lung. AB - In order to study oxidative stress in the lung, we have developed a rat lung slice model with compromised oxidative defences. Lung slices with markedly inhibited glutathione reductase activity (approximately 80% inhibition) were prepared by incubating slices, with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 microM) in an amino acid-rich medium for 45 min at 37 degrees. These lung slices had similar levels of GSH and ATP and polyamine uptake (a marker of alveolar epithelial type I and II cell function) to control rat lung slices. We have utilized these BCNU pretreated slices to study the effects of the herbicide, paraquat, in comparison to those of 2,3-dimethoxy-1,4-naphthoquinone, a potent redox cycler. Paraquat (10-100 microM) caused only minimal changes in the levels of GSH or ATP in control or compromised slices. In contrast, 2,3-dimethoxy-1,4 naphthoquinone caused a decrease in GSH in control slices but a markedly enhanced decrease in both GSH and ATP in compromised slices. Both compounds had only limited effects on putrescine and spermidine uptake in control slices. However, they caused a marked inhibition in compromised slices. Paraquat had little effect on 5-hydroxytryptamine uptake (a marker of endothelial cell function) in either control or compromised slices whereas the quinone inhibited uptake in the compromised slices. Thus, the lack of effect of paraquat on GSH and ATP does not support the involvement of oxidative stress in its toxicity. In contrast, using polyamine uptake, as a functional marker of alveolar epithelial cell damage, suggests a role for redox cycling. As paraquat is known to be accumulated primarily in alveolar type I and II cells (a small fraction of the lung cell population), our data suggest that only a small proportion of pulmonary GSH and ATP is present in alveolar epithelial type I and II cells but that much larger amounts may be present in endothelial cells. These studies highlight the problem of gross tissue measurements in heterogeneous tissues such as the lung. PMID- 2306272 TI - In vivo and in vitro effect of phenytoin on rat hepatic mixed function oxidases. PMID- 2306271 TI - Synergism between 4-hydroperoxycyclophosphamide and cisplatin: importance of incubation sequence and measurement of cisplatin accumulation. PMID- 2306273 TI - Muscarinic regulation of Ca2+ mobilization in a human salivary myoepithelial cell line. PMID- 2306274 TI - Isolation and characterization of a novel dihydrofolate formylating enzyme from human MCF-7 breast cancer cells. PMID- 2306275 TI - The effect of 90 days treatment with omeprazole on 24 hour plasma gastrin profiles in female Wistar rats. PMID- 2306276 TI - Arylamine N-acetyltransferase from fast (C57BL6) and slow (A/J) N-acetylating strains of mice. AB - Many drugs and xenobiotics which are arylamines or hydrazines are metabolized by N-acetyltransferase. The enzyme is polymorphically expressed in humans and inbred strains of laboratory animals can be classified as fast or slow acetylating strains. N-Acetyltransferase has been partially purified from livers from a fast acetylator, C57BL6, and a slow acetylator, A/J, strain of mouse. The enzyme has been purified 1900- and 955-fold, respectively from the two strains, but still represents less than 20% of the total protein. These studies show that at least 5000-fold purification is required to isolate mouse liver N-acetyltransferase from either strain. During purification, N-acetyltransferase from both strains of mice elute identically as a single peak on ion exchange chromatography. Sucrose density gradient centrifugation of N-acetyltransferase shows partial separation of the activity from A/J mice into two peaks whilst the enzyme from C57BL6 mice migrates as one peak which is distinct from both the major and minor types of N acetyltransferase in A/J mouse liver. The hydrodynamic parameters of N acetyltransferase from C57BL6 mice and the major peak of N-acetyltransferase from A/J mice show that these enzymes are likely to be monomers of apparent molecular weights 33,000 +/- 1000 and 30,000 +/- 2000, respectively. These results indicate that the N-acetyltransferase isozymes in liver of these two strains of mice are not identical. PMID- 2306277 TI - Concentrative uptake of digoxin by slices of chicken renal cortex. AB - The purpose of this investigation was to define, under controlled in vitro conditions, the processes contributing to the uptake and accumulation of [3H]digoxin by incubated slices of chicken renal cortex. Progressive uptake was evident in time-course experiments with the slice-to-medium concentration ratio (S/M) reaching 5.25 after 120 min. No metabolism was evident. Increasing the ratio of unlabeled to labeled digoxin resulted in a concentration-dependent decrease in relative uptake of the label, suggesting saturability. Incubation under conditions of metabolic inhibition reduced digoxin S/M by about 50%, indicating that both energy-requiring and passive mechanisms contribute to the overall accumulation process. The structural nature of the uptake process was explored by incubating digoxin in the presence of potential inhibitors of transport. The organic cation quinine and the non-glycosidic steroids digoxigenin and spironolactone were without effect even at greater than 1000-fold excess compared to digoxin. Similarly, the sugar digitoxose had no inhibitory activity on digoxin accumulation by the slices. On the other hand, the glycosides digitoxin, digoxigenin-bis-digitoxoside and digoxigenin-mono-digitoxoside inhibited dogoxin uptake in a concentration-dependent manner. These results indicate a structural preference for an intact glycoside rather than for either the steroidal or sugar portion of the molecule alone. An inhibitory effect of ouabain and a stimulatory effect of reduced medium potassium concentration suggest a possible role for Na+,K(+)-ATPase in the uptake of digoxin by the renal cortex. PMID- 2306278 TI - Oxidation of glycerol to formaldehyde by rat liver microsomes. Effects of cytochrome P-450 inducing agents. AB - Glycerol was shown recently to be metabolized to formaldehyde by microsomes from chowfed control rats (Winters et al., Biochem Biophys Res Commun 153: 612-617, 1988). In the present study, experiments were carried out to evaluate the oxidation of glycerol by microsomes isolated from rats treated with inducers of different isozymes of cytochrome P-450. The oxidation of glycerol to formaldehyde was increased in microsomes from rats treated with pyrazole, ethanol or acetone relative to their respective controls, but not after treatment with phenobarbital or 3-methylcholanthrene. This reaction was sensitive to inhibition by carbon monoxide and was inhibited by compounds known to be effective substrates for P 450j, e.g. aniline, ethanol, pyrazole and 4-methylpyrazole. Treatment with pyrazole caused an increase in Vmax for glycerol oxidation but did not affect affect the Km (about 15 mM) for glycerol, as compared to saline controls. Evidence that the product of glycerol metabolism is formaldehyde was provided by the observation that this product served as a substrate for the glutathione dependent formaldehyde dehydrogenase, and the amount of formaldehyde detected was identical to that detected by the Nash reaction. By utilizing [14C]glycerol, and coupling the formaldehyde dehydrogenase reaction to the formate dehydrogenase reaction, 14CO2 could be detected, indicating that the formaldehyde produced was derived from the added glycerol. These results suggest that that glycerol is not metabolically inert when added to microsomes but serves as an effective substrate for the cytochrome P-450j isozyme, extending the alcohol substrate specificity of this enzyme to poly-ols. The production of formaldehyde from glycerol may require caution since glycerol is often present in microsomal or reconstituted systems. PMID- 2306279 TI - Interactions between plasticizers and fatty acid metabolism in the perfused rat liver and in vivo. Inhibition of ketogenesis by 2-ethylhexanol. AB - Rates of ketone body (beta-hydroxybutyrate plus acetoacetate) production by perfused livers from starved rats were decreased about 60% from 39 +/- 2 to 17 +/ 3 mumol/g/hr by 2-ethylhexanol (200 microM), a primary metabolite of the plasticizer diethylhexyl phthalate. Inhibition of ketogenesis by ethylhexanol was dose dependent (half-maximal inhibition occurred with 25 microM) in the presence or absence of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Concentrations of beta-hydroxybutyrate relative to acetoacetate (B/A) increased in a step-wise manner from 0.32 to 0.75 in the effluent perfusate when ethylhexanol was infused. In contrast, the B/A ratio decreased in parallel with inhibition of ketone body production when alcohol dehydrogenase was inhibited. Pretreatment of rats with phenobarbital, an inducer of omega and omega-1 hydroxylases, diminished inhibition of ketone body production by low (less than 50 microM) of ethylhexanol. Thus, ethylhexanol is oxidized via phenobarbital inducible pathways to metabolites which do not inhibit ketogenesis. Studies were conducted to determine the site of inhibition of fatty acid oxidation by ethylhexanol. Rates of ketone body production in the presence of oleate (250 microM), which requires transport of the corresponding CoA compound into mitochondria, were reduced from 80 +/- 6 to 58 +/- 8 mumol/g/hr by ethylhexanol. In contrast, ketone body production from hexanoate, which is activated in the mitochondria, was not affected by ethylhexanol. Basal and oleate-stimulated rates of H2O2 production were not affected by ethylhexanol, indicating that peroxisomal beta-oxidation was not altered by the compound. Based on these data it is concluded that 2-ethylhexanol inhibits beta-oxidation of fatty acids in mitochondria but not in peroxisomes. Treatment of rats with ethylhexanol (0.32 g/kg, i.p.) decreased plasma ketone bodies from 1.6 to 0.8 mM, increased hepatic triglycerides and increased lipid predominantly in periportal regions of the liver lobule. These data indicate that alterations in hepatic fatty acid metabolism in periportal regions of the liver lobule may be early events in peroxisome proliferation. PMID- 2306281 TI - Oxygen dependence of oxidative stress. Rate of NADPH supply for maintaining the GSH pool during hypoxia. AB - NADPH supply for oxidized glutathione (GSSG) reduction was studied in hepatocytes under different steady-state O2 concentrations with controlled infusions of diamide, a thiol oxidant. When bis-chloro-nitrosourea (BCNU) was used to inhibit GSSG reductase, the rate of GSH depletion approximated the rate of diamide infusion, showing that diamide reacted preferentially with GSH under these experimental conditions. Under aerobic conditions without BCNU treatment, the GSH and NADPH pools were largely unaffected and little diamide accumulation or protein thiol oxidation occurred with diamide infusion rates up to 5.3 nmol/10(6) cells per min. However, at greater infusion rates, GSH and NADPH decreased, diamide and GSSG concentrations increased, and protein thiols were oxidized. This critical infusion rate was easily discernible and provided a convenient means to assess the capacity of cells to reduce GSSG as a function of O2 concentration. As the O2 concentration was decreased below 15 microM, the critical infusion rate decreased from the aerobic value of 5.3 to less than 2 nmol/10(6) cells per min in anoxic cells; half-maximal change occurred at 5 microM O2. Although cells could not maintain normal thiol and NADPH pools at infusion rates above the critical value, analysis of the rates of thiol depletion showed that the maximal NADPH supply rate for GSSG reduction under aerobic conditions was 7-8 nmol/10(6) cells per min and was affected by hypoxia to the same degree as the critical value. Thus, hypoxia and anoxia impair the capability of cells to supply NADPH for the reduction of thiol oxidants. This could be an important factor in the sensitivity of hypoxic and ischemic tissues to oxidative injury. PMID- 2306280 TI - Anthracycline resistance in murine leukemic P388 cells. Role of drug efflux and glutathione related enzymes. AB - Energy-dependent drug efflux is a major factor in cellular resistance of P388/R84 mouse leukemic cells to anthracyclines such as doxorubicin (DOX), and blocking of efflux increases sensitivity. However, efflux does not play a significant role in resistance to N-trifluoroacetyladriamycin-14-valerate (AD 32), a DOX analog. Since drug efflux alone cannot account for resistance to anthracyclines, we have, in the present study, measured cellular glutathione (GSH) content and activity of GSH cycle related enzymes to determine their role in resistance. Cellular GSH content was similar in DOX-sensitive and -resistant mouse leukemic cells (P388 and P388/R84). GSH peroxidase, glucose-6-phosphate dehydrogenase and glutathione reductase activities were 1.36-, 1.58- and 1.14-fold higher in P388/R84 cells. Incubation of P388/R84 cells with 100 microM buthionine-S,R-sulfoximine (BSO) for 24 hr reduced cellular GSH content to 6% of control and reduced their resistance to DOX [dose modification factor (DMF) 3.9]. GSH depletion had no significant effect on the cytotoxicity of AD 32 (DMF 1.5). Exposure of P388/R84 cells to BSO (for GSH depletion) and trifluoperazine (for efflux blocking) further reduced their resistance to DOX (DMF 14). These results indicate that DOX resistance in P388/R84 cells is multifactorial and that changes in GSH cycle related enzymes such as GSH peroxidase may also contribute to their resistance. PMID- 2306283 TI - Liver esterases and soman toxicity in the rat following partial hepatectomy. PMID- 2306282 TI - Uptake of chloroquine by human erythrocytes. AB - Analysis of studies of the pH dependence of the kinetics of chloroquine (CQ) uptake by human erythrocytes indicates that the unionised CQ species is the major membrane permeant at physiological pH even though the concentration of this species as a fraction of the total CQ concentration in solution is extremely small (0.01% at pH 7.4). CQ concentration-dependence studies and studies performed in the presence of various substrates and inhibitors of erythrocyte membrane transport failed to provide evidence of saturation or inhibition of CQ transport, which suggests that the likely mechanism of CQ transport across human erythrocyte membranes is by passive diffusion. Results of equilibrium binding studies of CQ to intact and lysed human erythrocytes indicated that the mechanism of CQ accumulation in intact human erythrocytes appears to be by a combination of ion trapping (a consequence of the basic nature of the drug and the pH gradient across the human erythrocyte membrane) and binding of CQ to cell components. PMID- 2306284 TI - Desulfuration of the insecticide parathion by human placenta in vitro. PMID- 2306285 TI - Inhibition of dapsone-induced methaemoglobinaemia in the rat. PMID- 2306286 TI - Sex-dependent sensitivity to dapsone-induced methaemoglobinaemia in the rat. PMID- 2306287 TI - The relative abilities of MPTP and MPP+ to compete with [3H]dopamine for the rat and marmoset striatal dopamine uptake site. PMID- 2306288 TI - The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. AB - To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in greater than or equal to 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned. PMID- 2306289 TI - Reduction of the risk of rheumatoid arthritis among women who take oral contraceptives. AB - Discrepant results among investigations of the association between oral contraceptive use and rheumatoid arthritis (RA) have been ascribed to shortcomings in the study methods. In the present study, we obtained detailed information on oral contraceptive use in 135 young women with confirmed definite or classic RA of recent onset and in 378 controls with soft tissue rheumatism or osteoarthritis. All patients had at least 2 years of followup to confirm the consistency of the diagnosis. Oral contraceptive use at any time before disease onset was reported by 70% of the RA patients and 85% of the controls; the latter figure corresponded to general population data for The Netherlands. This yielded a relative risk for RA of 0.39 among those who had ever used oral contraceptives and 0.58 for those using oral contraceptives at the time of symptom onset. The preventive effect of oral contraceptive use on the risk of RA was found to be independent of the dose, duration of use, or presence of HLA-DR4. The strongest protection was seen in women with a family history of RA and in women ages 31-40 at symptom onset. The conflicting results in the literature are discussed, and a possible biologic mechanism for this phenomenon is suggested. PMID- 2306290 TI - High prevalence of IgA rheumatoid factor in severe polyarticular-onset juvenile rheumatoid arthritis, but not in systemic-onset or pauciarticular-onset disease. AB - The presence of IgA rheumatoid factor (IgA-RF) has been correlated with severe joint disease in adult rheumatoid arthritis (RA), but IgA-RF has not been reported in juvenile rheumatoid arthritis (JRA). In the present study, IgA-RF was assayed by an enzyme-linked immunosorbent assay and was found in the sera of 14 of 24 children (58%) with active polyarticular JRA. The presence of IgA-RF correlated with the degree of functional disability. In contrast, IgA-RF was not found in the sera of systemic-onset disease patients, regardless of the degree of dysfunction. IgA-RF was detected in only 1 patient with pauciarticular disease, despite the fact that several patients in this group had severe disease. The presence of IgA-RF in polyarticular JRA did not correlate with serum IgA levels, but did correlate with the presence and the level of serum IgM-RF. Thus, the presence of IgA-RF appears to be specific for polyarticular JRA, and shows a correlation with severe disease in this group. PMID- 2306291 TI - Subsequent behavior of users of an arthritis information telephone service. AB - Followup telephone interviews were conducted with a stratified random sample of 305 users of a prototype telephone information service for arthritis 2-4 months after their initial contact with the service. The percentage of respondents who reported taking at least 1 positive action for their arthritis because of service usage was 79%. The most frequently reported actions of users were asking their doctor more questions and greater compliance with their doctor's orders. About one-half of the respondents felt more in control of their arthritis because of service usage. Both the taking of at least 1 action and the taking of certain specific actions were significantly correlated with feeling more in control of the arthritis (P less than 0.01). Respondents who were less than 60 years old, black, or symptomatic were significantly more likely to take an action and took significantly more actions (P less than 0.01). This minimal intervention may stimulate positive behaviors for individuals with arthritis. PMID- 2306292 TI - Regression of bone and cartilage loss in adjuvant arthritic rats after treatment with cyclosporin A. AB - To test the effect of cyclosporin A (CsA) on arthritis-related bone resorption, we studied 30 female rats with adjuvant-induced arthritis (AIA). The animals were randomly assigned to 5 groups of 6 animals each; they received daily oral doses of 3, 5, 10, or 15 mg/kg CsA or placebo for 10 days. The parameters studied were (a) caliper measurements of hindpaw swelling, (b) radiometric densitometry of caudal vertebrae, (c) quantitative histomorphometry of radiographed vertebrae, and (d) glycosaminoglycan measurements in femoral condyles. A significant dose dependent regression of articular swelling occurred in rats given 5, 10, and 15 mg/kg CsA, and this was concomitant with improvement in bone density. These results correlated with those of quantitative bone morphometry. Thus, trabecular volume was significantly reduced in AIA rats, but restoration to virtually normal values occurred with CsA doses between 5 and 15 mg/kg. The protective effect of CsA on articular damage was supported by the dose-dependent progressive improvement in total femoral condyle glycosaminoglycan content. The favorable effect of CsA on AIA is likely due to a blockade of T cell activation via an inhibition of production of lymphokines such as interleukin-2 and gamma interferon. The consequent cessation of the immune reaction would lead to a reduction in the release of cytokines, such as interleukin-1, that are likely to be the mediators of the pathologic bone and cartilage breakdown that is characteristic of arthritic disease. PMID- 2306293 TI - Induction of an acute erosive monarticular arthritis in mice by interleukin-1 and methylated bovine serum albumin. AB - We examined the effect of interleukin-1 (IL-1) administration on a mild and transient inflammatory response in the knees of mice injected intraarticularly with methylated bovine serum albumin (mBSA). Injection of mBSA on day 0 into nonsensitized mice caused a weak inflammatory response confined to the infrapatellar fat pads and involved infiltration by mononuclear cells, neutrophils, and eosinophils. The response developed between days 4 and 7 and resolved by day 28. No erosion of cartilage or subchondral bone was seen. In contrast, mBSA-treated mice injected with recombinant human IL-1 beta subcutaneously in the ipsilateral footpad on days 0-3 developed a severe monarticular arthritis in the antigen-injected knee. Pannus developed, extending over the articular surfaces, and extensive erosion of cartilage and subchondral bone occurred. Multinucleated giant cells, together with fibrin-like material, were observed at sites of active bone erosion and debris, and large numbers of neutrophils were seen in the joint space. These pathologic features represent a new arthritis model in which IL-1 profoundly augments a weak inflammatory response and induces acute erosive joint destruction, supporting the hypothesis that IL-1 is an important cytokine in the pathogenesis of arthritis. PMID- 2306294 TI - Chronic acquired immunodeficiency syndrome-associated arthritis: a synovial ultrastructural study. AB - We describe a patient who developed acquired immunodeficiency syndrome-related complex, complicated by chronic, symmetric polyarthritis. Synovial biopsy showed large areas of plasma cell infiltration subjacent to the synovial lining. Ultrastructural study demonstrated tubuloreticular structures within endothelial cells, crystal-like inclusions in plasma cells, and virus-like particles located around synoviocyte fragments. Although immunologic and morphologic studies did not permit classification of these virus-like structures, the role of these possible virions in the pathogenesis of the observed synovitis remains to be determined. Surprisingly, the patient's chronic arthritis resolved with anti retroviral treatment (azidothymidine: AZT). PMID- 2306295 TI - Accuracy of creatinine clearance in measuring glomerular filtration rate in patients with systemic lupus erythematosus without clinical evidence of renal disease. AB - We sought to determine whether creatinine clearance (Ccr) gives an accurate measurement of the glomerular filtration rate in patients with systemic lupus erythematosus (SLE) with no clinical evidence of renal disease. Eighteen such SLE patients underwent measurement of Ccr and 99mtechnetium-DTPA clearance (CDTPA). The mean +/- SD Ccr:CDTPA ratio was 1.12 +/- 0.15 (95% confidence interval 1.04 1.20). These results indicate that Ccr gives an accurate measurement of the glomerular filtration rate in the majority of SLE patients who do not have clinical evidence of renal disease. PMID- 2306296 TI - Learned helplessness in systemic lupus erythematosus: analysis using the Rheumatology Attitudes Index. AB - The Rheumatology Attitudes Index (RAI) was administered to 138 patients with systemic lupus erythematosus (SLE) to determine its reliability and to examine the construct of learned helplessness in patients with this disease. The internal consistency of the RAI was indicated by Cronbach's standardized alpha value (alpha = 0.70). Significant correlations were observed between RAI scores and the Modified Health Assessment Questionnaire Activities of Daily Living difficulty (r = 0.34, P less than or equal to 0.001) and dissatisfaction (r = 0.32, P less than or equal to 0.001) scores, the 10-cm visual analog pain scale (r = 0.42, P less than or equal to 0.001), and the Psychosocial Adjustment to Illness Scale raw total (r = 0.63, P less than or equal to 0.01). These findings support the external validity of the RAI in SLE. In addition, these data suggest that the learned helplessness construct might be relevant to the outcomes of morbidity and mortality in patients with SLE. PMID- 2306297 TI - DNA autosensitivity in two Japanese sisters. AB - Two cases of DNA autosensitivity in Japanese sisters are reported. Both patients developed painful ecchymoses and other bleeding disorders. Skin tests with autologous leukocyte lysates and calf thymus DNA produced intermediate-type reactions that were identical to spontaneous skin reactions. Pretreatment of DNA with either DNase or chloroquine sulfate inhibited these reactions. Our studies suggest that anti-DNA antibodies might contribute to the clinical symptoms of this disorder. PMID- 2306298 TI - Comparison of cemented and cementless hip and knee replacements. PMID- 2306299 TI - Acute myositis in a patient with the acquired immunodeficiency syndrome. PMID- 2306300 TI - Restricted clonality of T cells in the joints of rheumatoid arthritis patients. PMID- 2306301 TI - The prevalence of Lyme disease in an endemic region. PMID- 2306302 TI - Comment on the article by Duston et al. PMID- 2306303 TI - Subacute cutaneous lupus erythematosus during psoralen ultraviolet A therapy. PMID- 2306304 TI - The prevalence of hearing impairment. PMID- 2306305 TI - Lipoprotein changes and increased affinity of LDL for their receptors after acipimox treatment in hypertriglyceridemia. AB - Modifications in plasma low and high density lipoprotein (LDL and HDL) subfraction distribution, as well as the regulation of cellular LDL metabolism by hypertriglyceridemic LDL were tested before and after treatment with acipimox, a nicotinic acid derivative, in 11 type IV hyperlipidemic patients. Large, less dense LDL particles were found in plasma after acipimox treatment, reflecting compositional changes, characterized by a 25.4% increase in cholesteryl ester content and by a 46.2% reduction of triglycerides in LDL. HDL subfractions were only slightly modified, with an increase of dense, cholesteryl ester-enriched and triglyceride poor HDL3 particles. The LDL (B,E) receptor activity in humans skin fibroblasts of LDL isolated before and after treatment was also evaluated. Hypertriglyceridemic LDL proved rather inefficient in regulating receptor activity with a close to 30% reduction vs. normal LDL in the capacity to inhibit receptor-mediated uptake and degradation of 125I-LDL. Such abnormality was fully corrected after acipimox. The reported findings indicate that acipimox treatment in type IV patients, in spite of a relatively modest plasma triglyceride reduction, can markedly modify LDL distribution and composition, normalizing the defective interaction of hypertriglyceridemic LDL with the LDL (B,E) receptor. PMID- 2306306 TI - Intralipid infusion in patients with familial hypercholesterolemia. Effect of serum and plasma lipoproteins on platelet aggregation and on macrophage cholesterol metabolism. AB - Intralipid infusion into normal volunteers was recently shown to possess anti atherogenic properties. We studied the effect of intralipid infusion in patients with severe Familial Hypercholesterolemia (FH) refractory to conventional therapy. FH patients and normal subjects, who served as controls, were given an intravenous infusion of intralipid for 6 h. Serum samples taken from both groups before, during and after intralipid infusion were studied for their ability to inhibit cellular cholesterol accumulation by macrophages. A significantly lower rate of cellular cholesterol esterification (of 46%, P less than 0.005 and 44%, P less than 0.005 in patients and normals, respectively) was demonstrated in macrophages incubated with serum obtained during intralipid infusion compared to those incubated with preinfusion serum. The maximal effect was demonstrated with serum samples taken at the end of the infusion, but the inhibitory effect persisted even at 24 h post-infusion. It was found that chylomicron like particles could induce the above-mentioned effects on macrophage cholesterol esterification. A significant decrement of 50% (P less than 0.005) in aggregation of platelets isolated from plasma samples taken during and after intralipid infusion from both groups was demonstrated, when compared to platelets isolated in the preinfusion state. This effect persisted 18 h subsequent to infusion. We conclude that intralipid infusion abolishes serum ability to stimulate cholesterol esterification in cultured macrophages, and exhibits inhibitory effects upon platelet aggregation. If similar events occur in the arterial wall, intralipid might inhibit foam cell formation. PMID- 2306307 TI - Some possible effects of dietary monounsaturated fatty acids on cardiovascular disease. PMID- 2306308 TI - Plasmapheresis in patients with familial hypercholesterolemia lowers ionized calcium but does not deteriorate left ventricular function. PMID- 2306309 TI - Health care management. A tool for the future. AB - As a result of increasing health care costs in the U.S., the skilled, knowledgeable occupational health nurse can implement a plan to reduce these costs with benefits personnel. Using accepted business principles such as the Deming/Shewart cycle, health data can be obtained from the provider, trends can be analyzed, and strategies can be planned for the population. Health and subsequent costs can be managed through the use of the natural history of disease, the three levels of prevention, occupational health nurses' relationships with people, and their access to confidential data. Short-term strategies should include catastrophic and intermediate case management. These systems ensure results in terms of quality and cost. PMID- 2306310 TI - A worksite parenting program. AB - With more and more companies offering wellness programs for their employees, it seems reasonable to offer parent training classes to employees as an educational tool and a means of coping with stress. A series of parenting classes was developed using the STAR Parenting Model. The STAR Model teaches parents to stop, think, ask, and respond to their children based on tenets of cognitive behavior management. Classes taught to faculty and staff of the university were well attended and participants indicated that the method positively altered their parenting practices. Parents are challenged by their young children and by their jobs and careers. Parenting education at work may help to ease some employee stress and improve their parenting practices. PMID- 2306311 TI - Psychosocial assessment of the high utilizer of occupational health services. AB - A small group of persons in ambulatory care settings report multiple symptoms and recurrent distress and utilize a high percentage of resources. Often these high utilizers are requesting help with a psychosocial problem through their symptoms. The psychosocial reason for high utilization of services may be a major psychiatric problem such as a somatization disorder or a depression/anxiety disorder. Most often, however, the person is seeking help with family or work stresses or is in need of information and/or reassurance. A careful assessment by the occupational health nurse can lead to a determination of an unmet psychosocial need. Direct help with this problem can break the cycle of multiple symptoms, distress, and utilization. PMID- 2306312 TI - The need for occupational health nurses in nonindustrial settings. Results of a national survey. AB - A survey was done to determine the current and future demand for occupational health nurses in the nonindustrial settings of multi-specialty group medical practices and HMOs in the U.S. The results regarding future demand indicate a growth rate for the number of positions for occupational health nurses in these settings at greater than 300% in the coming decade. The present low number of graduates from occupational health nursing education programs make it unlikely that this demand can be met, a situation which will have serious adverses consequences for the health of the American work force. PMID- 2306313 TI - A conceptual model of occupational health nursing. AB - Occupational health nurses can practice and research in their profession better if they approach occupational health nursing with a well developed conceptual model. The Wilkinson Windmill Model is one conceptualization of occupational health nursing an occupational health nurse may use for guidance in practice, research, and education. The model consists of five primary components. This conceptual model may be a useful framework for understanding the role of the occupational health nurse in many different environments and may prove valuable as a tool for conducting research. PMID- 2306315 TI - Medical school admission. PMID- 2306314 TI - Public health in the workplace. Part II: liability issues confronting the occupational health nurse. PMID- 2306316 TI - Perspectives on medical school admission. AB - This article is the author's formulation of important issues concerning medical school admission: that (1) in recent years, almost all applicants who have been admitted to medical school have obtained the M.D. degree and been licensed to practice; (2) given this high success rate, an accepted applicant's economic security is virtually guaranteed; (3) the admission decision contributes directly to the formation of a highly paid, high-status professional elite; (4) the link between students' academic aptitude for medical education and their achievement in medical school is weak; (5) schools pay lip-service to the importance of students' character, motivation, and other personal qualities but continue to select students with high grades in science courses and high MCAT scores; (6) admission officers and committees often confuse selecting students with predicting their achievement in medical school; (7) two core values in American culture (self-reliance and competition) encourage the use of norm-referenced measurement in all phases of education; and (8) there are alternatives to the traditional approach to defining eligibility for professional education. PMID- 2306317 TI - The interview: one more life? PMID- 2306318 TI - Moral dilemmas in medical school admission. AB - The wide range of complex moral and ethical issues of medical school admission committees are seldom publicly acknowledged, reflected upon, analyzed, or discussed, although they are faced regularly. Three cases are presented that illustrate some of the common and unusual moral dilemmas in the admission process. These issues and several practical strategies for ethical decision making are discussed, along with their limitations and weaknesses. These practical strategies are applied to the three cases to see what solutions might be offered. PMID- 2306319 TI - A matching program for medical school admissions. PMID- 2306320 TI - Recruitment and preparation program for Hispanic applicants. PMID- 2306322 TI - Personality types of family practice residents in the 1980s. AB - This study was based on a nationwide sample of 778 family practice residents in the mid-1980s and was conducted to determine the personality types that were most common among those residents. The results showed that the single most common personality type was that in which the individual prefers to see the world in terms of challenges and future possibilities and to make decisions based upon his or her subjective values. These results showed that the sample differed significantly in Myers-Briggs personality type from both the general practitioners of the 1950s and the early family practice residents of the 1970s, who preferred to see the world in terms of the immediate facts of experience and to make decisions objectively. There were also significant differences between the civilian and military family practice residents, but not between the community-based and university-based residents. Implications regarding future practice styles, physicians' personal values, and manpower needs are discussed. PMID- 2306321 TI - The controllable lifestyle factor and students' attitudes about specialty selection. AB - Questionnaires were distributed to 346 fourth-year students in nine medical schools. The students were asked to state their selected specialty and to rank the importance that each of 25 influences, listed as questionnaire items, had had in making their choice of specialty. Factor analysis showed that particular items were significantly associated with particular factors. The first factor emphasized perceived lifestyle (items in this category gave importance to remuneration, personal time, and prestige); the second factor emphasized cerebral activities and a practice orientation; and the third factor stressed altruistic values and attitudes. The authors classified the selected specialties into three groups: those characterized as having a non-controllable lifestyle (NCL), those with a controllable lifestyle (CL), and surgery. (CL specialties were defined as those that allow the physician to control the number of hours devoted to practicing the specialty.) Data were analyzed using factor analysis, and analysis of variance, and the Scheffe method. Analysis indicated that the perceived lifestyle factor was most closely associated with the responses of those students choosing CL specialties. Furthermore, this factor received the highest total loading of the three factors from all the students, thus indicating the level of interest in lifestyle factors. Responses to items that defined the cerebral and practice factor were highest from the group of students choosing CL specialties and lowest from the group choosing NCL specialties. The NCL students scored highest in the altruism factor and the CL students scored the lowest. The surgery and NCL groups were similar in attitude patterns, and both were substantially different in attitude patterns from those of the CL groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306323 TI - The declining applicant pool and MCAT scores. PMID- 2306324 TI - Clinical case updates. Selected case studies of wounds treated with Lyofoam. PMID- 2306325 TI - The epidemiology and management of skin tears in older adults. PMID- 2306326 TI - A report of clinical investigation of various tissue support surfaces used for the prevention, early intervention and management of pressure ulcers. PMID- 2306327 TI - Multidisciplinary team approach to skin care. PMID- 2306328 TI - Contracture and pressure necrosis. PMID- 2306329 TI - Nursing assistants make the difference in effective skin care. PMID- 2306330 TI - Cerebral laterality and depression: relations of perceptual asymmetry to outcome of treatment with tricyclic antidepressants. AB - The relationship of cerebral laterality to outcome of treatment with antidepressants was examined by comparing perceptual asymmetry in subgroups of depressed patients formed on the basis of clinical response to a tricyclic antidepressant (TCA) or a monoamine oxidase inhibitor (MAOI). Perceptual asymmetries of 63 unmedicated depressed patients were assessed for verbal and nonverbal tasks, using dichotic listening and visual half-field methods, and retests were obtained on 49 patients after about 6 weeks of treatment. There were significant differences between TCA responders and TCA nonresponders in dichotic listening and visual field asymmetries. Differences in perceptual asymmetry were specific to TCAs, in that no comparable differences existed between MAOI responders and MAOI nonresponders. Although perceptual accuracy improved following successful TCA treatment, abnormal perceptual asymmetries in TCA responders were present before and after treatment and may thereby represent state-independent characteristics. PMID- 2306331 TI - Effect of zopiclone and midazolam on sleep and EEG spectra in a phase-advanced sleep schedule. AB - Midazolam (15 mg), a benzodiazepine (BDZ) hypnotic, and zopiclone (7.5 mg), a non BDZ hypnotic, were administered to young, healthy subjects prior to bedtime. They went to bed at 2300 hours after taking placebo (PL-23), and then on three occasions at 1900 hour after taking placebo (PL-19) or one of the hypnotics. Advancing bedtime by 4 hour increased the combined value of waking, stage 1, and movement time. Compared to PL-19, both drugs reduced sleep latency and stage 3, and increased stage 2. Spectral analysis of the EEG in non-rapid-eye-movement sleep revealed a declining trend of power density in the low-frequency range in the course of the night. Activity in the 1 to 10 Hz range was markedly depressed by the two hypnotics, whereas activity in the spindle range (11 to 14 Hz) was augmented. The former changes persisted throughout the 12-hour recording period. The fact that both hypnotics bind to BDZ receptors could be responsible for the similar effects on the EEG spectra. PMID- 2306332 TI - Melatonin administration in insomnia. AB - Ten patients with persistent insomnia were randomized in a double-blind design and the effects of 1-mg and 5-mg oral dosages of melatonin on the electroencephalogram-recorded sleep were examined. Subjects showed no changes in either the onset or duration of sleep, nor any effect on mood or alertness the following day. A significant increase in rapid-eye-movement (REM) latency was noted at the 1-mg dose, though no other parameter of REM sleep was affected. The patients reported less sleep on both melatonin conditions. Despite this perception of decrease, overall subjective quality was reported to be improved. PMID- 2306333 TI - Human platelet [125I]R-DOI binding sites. Characterization by in vitro autoradiography. AB - We quantified binding sites for 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), a 5-HT2 agonist and hallucinogen, in human platelets. We incubated sections from human platelet pellets with [125I]R-DOI with or without 1 mumol/L ketanserin, followed by autoradiography and computerized microdensitometry. We corrected the values of binding density by the protein content of each section with a densitometric protein assay. The present method revealed a single class of high affinity binding sites for [125I]R-DOI, with a Kd of 6.4 +/- 0.7 nmol/L and a Bmax of 100 +/- 10 fmol/mg protein. Kd and Bmax for [125I]R-DOI determined by the classical membrane binding assay, were 2.7 +/- 0.4 nmol/L and 100 +/- 10 fmol/mg protein, respectively. The present method is precise, very sensitive, and allows the characterization of [125I]R-DOI binding in sections obtained from as little as 3 ml of blood. Standardization is possible after correction by the protein content of each individual section. PMID- 2306334 TI - [Antigenicity and allergenicity of acarians. Study of 7 varieties in a population of 33 allergic patients]. AB - A population of 33 patients who were known to be sensitive to mites were studied by the authors to establish whether 7 types of mites were responsible. A complementary and comparative study by the same Immunology laboratory compared the RAST and TDBH values as an addition to the skin test responses. The role of storage mites seemed to be sufficiently clear to advise increase in systematic research. The discovery of possibly frequent presence of Pyroglyphus africanus was a discovery that justifies other epidemiological and ethnic investigations. PMID- 2306335 TI - [Non-specific hypersensitivity from membrane instability of target cells is based on disequilibrium of trace elements?]. AB - Non-specific hypersensitivity from target cell membranes instability sometimes causes a syndrome of acute cutaneous-mucosal problems, which are not found in the usual list of real allergies: no atopic history; no criteria of unity of time or place of action; no allergy equivalent of the atopic series; no individual allergen; absence of the biological criteria of allergy. The body levels of 16 oligo-elements in the capilliaries of patients is reflected in the common anomalies that seem to be involved in the dis-equilibrium of the membrane stability. Deficiency of manganese, iron, magnesium and zinc are most often found. A complementary therapeutic scheme seems to be useful to resolve the situation. PMID- 2306336 TI - [Allergy to kiwi: an unrecognized allergy]. AB - We reported 4 cases of an uncommon hypersensitivity: hypersensitivity to kiwi fruit. The clinical reactions, essentially buccal, occurred few minutes after ingestion of the fruit. The Radio Allergo Sorbent Test were positive in the 4 cases. The skin tests, with fresh extracts of kiwi, made in 3 cases were dramatically positive, while they are negative in controls patients. The kiwi fruit initially comes from China, but is now produced in France, and especially in Poitou-Charente. It contains a proteolytic enzyme call Actinidin with physical and chemical properties similar to those of Papain, who can perhaps explain this hypersensitivity. PMID- 2306337 TI - [Does the allergic child become sensitized to small domestic mammals (guinea pig, hamster, rabbit?)]. AB - Our own works show among allergic children a frequency of sensitization of 30% to cats and of 17% to dogs. But, the proportion of sensitizations to other small domestic mammals such as guinea pigs, hamsters of rabbits seems to be unknown. Among atopic children with a known contact with those pets we noted: for guinea pig: 29% positive cutaneous or RAST tests 21% clinical signs in presence of animals; for hamster respectively 28% and 6.5%; for rabbit respectively 18% and 12.3%. Guinea pigs seem to be more sensitizing animals, followed by rabbits, then by hamsters. As for cats and dogs, eviction is imperative when a sensitization is demonstrated. PMID- 2306338 TI - [When the allergist profession joins the detective profession. (An observation about corn dusts)]. PMID- 2306339 TI - Enhanced sympathetic pressor responses to intracerebrovascularly infused saline in awake salt-loaded rats. AB - Osmotic minipumps were used to infuse hypertonic saline intracerebroventricularly into conscious rats fed high-salt diets to determine if combining high-salt intake with ICV saline infusion would elevate blood pressure more than either procedure alone. Mean aortic pressures became progressively elevated in all rats infused with saline and the magnitude of the elevation was significantly larger in those fed high-salt diets instead of the regular chow. Added pressor effects of high-salt feeding were unaffected by pharmacologic vasopressin or angiotensin blockade thereby indicating that humoral mediation by either peptide was not involved. A general increase in cardiovascular reactivity also seemed unlikely since pressor responsiveness to injected norepinephrine did not differ between rat groups. Sympathetic hyperactivity was considered to be a logical explanation because enhancement by high-salt feeding was abolished following either ganglion blockade with pentolinium or chemical sympathectomy with 6-hydroxydopamine. These findings are compatible with the interpretation that high-salt feeding enhanced pressor responses to centrally-infused saline by increasing sympathetic vasomotor tone. PMID- 2306340 TI - High K diets markedly reduce atherosclerotic cholesterol ester deposition in aortas of rats with hypercholesterolemia and hypertension. AB - High K diets prevent hypertensive endothelial injury and intimal thickening. Cholesterol esters often deposit during hypercholesterolemia. Would a high K diet influence cholesterol ester deposits? In a normal rat on a normal diet, no cholesterol esters are detected in the aorta. Stroke prone SHR rats were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats had normal (.5%) K in the diet. Another group of 10 rats ate high (2.1%) K. Mean intraarterial blood pressures averaged 165 mm Hg in the normal K group and 161 mm Hg in the high K group (P = NS). The serum cholesterol averaged 229 mg/dL in the normal K group and 214 in the high K group (P = NS). Total aortic cholesterol esters per rat involving 16 and 18 carbon chain fatty acids averaged 187 micrograms in normal K v 68 micrograms in high K, measured by gas chromatography. These were the main esters; other esters were negligible. Thus high K reduced cholesterol ester deposits by 64% (P less than .0003), even though blood pressure and cholesterol levels were quite similar in the two groups. Both high cholesterol and high BP injure endothelial cells and increase invasion of macrophages and vascular smooth muscle cells into the intima and increase endothelial permeability to proteins. With high plasma cholesterol, these processes lead to atherosclerosis with cholesterol ester deposition. The high K diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could possible be useful for preventing atherosclerotic complications such as heart attacks in human hypertension. PMID- 2306341 TI - New evidence on the role of sodium in hypertension. The Intersalt Study. PMID- 2306342 TI - Light affects neonatal rat pineal gland N-acetyltransferase activity by an extra retinal mechanism. AB - To determine whether extra-retinal mechanisms mediate photoperiodic changes in neonatal rat pineal gland N-acetyltransferase activity, 4-day-old intact or bilateral orbital enucleated rats were killed during the dark phase of the lighting cycle, either in darkness or following 4 hr exposure to fluorescent light. Light suppressed the high nighttime N-acetyltransferase activity equally in intact and enucleated pups. Subsequent studies showed that at least 0.5 hr exposure and nocturnal illuminances of 109 microW/cm2 or greater were required to cause statistically significant reductions in the activity of the enzyme in 4-day old rats. Taken together, these data indicate that relatively intense environmental light can affect neonatal rat pineal gland biochemistry via extraretinal mechanisms. PMID- 2306343 TI - 'Nothin' remains quite the same'. PMID- 2306344 TI - Endoscopic transnasal orbital decompression. AB - Orbital decompression for dysthyroid orbitopathy has traditionally been performed through either an external or a transantral approach. The advent of intranasal endoscopes allowed for the development of a transnasal approach for medial and inferior orbital wall decompression. Using this approach, orbital decompressions were performed on 13 orbits in eight patients with severe complicated dysthyroid orbitopathy. Simultaneous bilateral lateral orbitotomies were performed on five patients. Walsh-Ogura decompressions and lateral orbitotomies were performed on two orbits. When combined with lateral orbitotomy, Hertel measurements improved an average of 5.7 mm in orbits decompressed transnasally and 4.5 mm in orbits decompressed with a Walsh-Ogura approach. Transnasal decompression alone improved Hertel measurements an average of 4.7 mm. Visual acuity improved in three of four patients with optic neuropathy, and in all patients with exposure keratopathy. We conclude that the endoscopic transnasal approach provides comparable decompression to traditional methods while avoiding the morbidity of an external ethmoidectomy or Caldwell-Luc antrotomy. PMID- 2306345 TI - Turbinate hypertrophy. Evaluation of the nasal cavity by acoustic rhinometry. AB - We used acoustic rhinometry to assess the geometry of the nasal cavity. The cross sectional area of the nasal cavity as a function of distance from the nostrils was obtained. Seventeen patients with hypertrophy of the inferior turbinate and septal deviations were examined preoperatively and postoperatively; 34 normal subjects served as controls. The cross-sectional area at the anterior part of the nose suggested that skeletal hypertrophy of the inferior turbinate might be expected in the side opposite the main septal deviation. Unilateral inferior turbinoplasty seems advisable. PMID- 2306346 TI - Malignant tumors of major salivary gland origin. A matched-pair analysis of the role of combined surgery and postoperative radiotherapy. AB - Between 1966 and 1982, 46 patients with previously untreated malignant tumors of major salivary gland origin received combined surgery and postoperative radiotherapy. They were compared with 46 patients treated with surgery only between 1939 and 1965, who were matched according to prognostic criteria. Radiation doses ranged from 4000 to 7740 cGy (median, 5664 cGy). The 5-year determinate survival rates for patients given combined therapy with stage I and II disease vs patients given surgery only was 81.9% vs 95.8%, while for stages III and IV it was 51.2% vs 9.5%, respectively. Local control for stage III and IV disease in patients given combined therapy vs patients given surgery only at 5 years was 51.3% vs 16.8%. For patients with nodal metastases, 5-year determinate survival for the combined-therapy group vs the surgery-only group was 48.9% vs 18.7%, and the corresponding local-regional control was 69.1% vs 40.2%. The results of this analysis suggest that postoperative radiotherapy significantly improves outcome for patients with stage III and IV disease and for patients with lymph node metastases. PMID- 2306347 TI - Calcium regulation of antigen expression on normal and malignant human squamous cells in vitro. AB - In vitro, normal keratinocytes exhibit undifferentiated morphologic features and proliferate for multiple passages in low-calcium medium (less than or equal to 0.3 mmol/L) whereas, in high-calcium medium (greater than or equal to 1.0 mmol/L), these cells assume differentiation characteristics, begin to stratify, and eventually cease proliferating. In contrast, malignant keratinocytes grow well in high-calcium medium. Expression of pemphigus vulgaris antigen, a squamous cell marker, is altered on cultured normal keratinocytes by calcium. In this study we compared the effects of calcium levels on expression of cell surface antigens by UM-SCC-38, a human squamous carcinoma cell line, and normal keratinocytes cultured from newborn foreskin. Pemphigus, pemphigoid, beta 2 microglobulin antigens, as well as the epidermal growth factor receptor and the A9 germinal epithelial cell basement membrane squamous carcinoma antigen were examined. Pemphigus antigen was strongly expressed on normal and malignant cells in high-calcium but not low-calcium medium. Calcium concentration did not affect the expression of any of the other antigens tested. Thus, although calcium induces differentiation and eventual loss of proliferative capacity in normal but not malignant keratinocytes in vitro, we were unable to demonstrate differences in pemphigus vulgaris antigen expression that might be linked to the growth inhibitory effects induced by high calcium levels in nontransformed epithelial cells in culture. PMID- 2306348 TI - Blood transfusion and other risk factors for recurrence of cancer of the head and neck. AB - To determine whether perioperative blood transfusion affected the recurrence rate of squamous cell cancer of the head and neck, we performed a retrospective study of all patients with stage III and IV disease treated surgically at the University of North Carolina, Chapel Hill, between 1983 and 1986. Those who recurred were compared with those who did not in regard to 16 prognostic variables, including whether or not they had received a perioperative blood transfusion. Analyzing each variable separately, five were significantly related to recurrence. These were (1) surgical margin status, (2) stage, (3) presence of pathologically positive nodes, (4) blood transfusion status, and (5) type of treatment. However, because several of these variables were clearly interrelated, the same data were subjected to a multivariate regression analysis specifically designed to identify significant prognostic variables independent of their association with other variables. By this analysis, only margin status and the presence or absence of a blood transfusion were statistically significant predictors of recurrence. PMID- 2306349 TI - Inflammatory torticollis in children. AB - Acute torticollis is commonly seen in the pediatric emergency department. It often results from an inflammatory process that irritates the cervical muscles, nerves, or vertebrae. Posturing of the head occurs with unilateral spasm of the sternocleidomastoid muscle such that the child will position the head with the occiput rotated to the affected side and the chin rotated to the contralateral side. We recently treated 26 children who presented to the emergency department with acute nontraumatic torticollis. The most common causes were upper respiratory infection, sinusitis, otomastoiditis, cervical adenitis, and retropharyngeal abscess or cellulitis. Four patients had subluxation of the atlantoaxial joint as a result of the inflammatory process. Children with acute torticollis need careful evaluation for either overt or occult otolaryngologic infections. Computed tomography and magnetic resonance imaging are helpful in determining the cause of the acute torticollis and in ruling out rotatory subluxation of the atlantoaxial joint. PMID- 2306350 TI - Ear surgery in osteogenesis imperfecta. Clinical findings and short-term and long term results. AB - Preoperative and postoperative hearing results and long-term results of stapedectomy have been investigated in 58 ears (47 patients) with osteogenesis imperfecta. After 3 months, hearing gain had been achieved in 49 (85%) of 58 ears. Twenty-seven (68%) of 40 ears followed up for an average of 9.6 years (range, 2 to 24 years) had no deterioration of their immediate postoperative hearing gain. In the other ears, the decrease in hearing gain in the long term was due to progression of the sensorineural component of the hearing loss. Complete closure of the air-bone gap remained unchanged in 26 (70%) of 37 ears. In 5 (9%) of 58 ears the sensorineural component of the hearing loss increased as an immediate result of the operation. In 6 other ears (10%) progressive sensorineural hearing loss was seen only after more than 1 year. A natural course of the disease is assumed as the cause because progressive sensorineural hearing loss has also been seen in the nonoperated on contralateral ears of these patients. PMID- 2306351 TI - Influence of nasal allergic reactions on the clearance of middle ear effusion. AB - In order to investigate the influence of nasal allergic reactions on the clearance of middle ear effusion, an animal model of nasal allergy and otitis media with effusion was produced in the same guinea pigs simultaneously by passive sensitization with serum of homologous animals containing IgE antibodies (for nasal allergy) and by inoculation of immunocomplex into the tympanic cavity (for otitis media with effusion). Usually, middle ear effusion appeared within 2 to 3 days and disappeared within 7 to 9 days after the inoculation of immunocomplex. Three days after the inoculation of immunocomplex, intranasal antigen challenge was performed three times daily and continued until the animals were killed. Disappearance of middle ear effusion appeared to be delayed in animals in which nasal allergic reactions were induced. Middle ear effusion was not found in those ears that were not inoculated with immunocomplex. Findings of the present study indicate that IgE-mediated allergic reactions of the mucous membrane lining the nose, nasopharynx, and eustachian tube constitute a factor indicative of a chronic state of disease, rather than a cause of otitis media with effusion. PMID- 2306352 TI - Bacterial antigens and neutrophil granule proteins in middle ear effusions. AB - Otitis media with effusion is a significant cause of hearing loss in young children. We hypothesized that persistent bacterial antigens in middle ear effusions (MEEs) might act as chronic inflammatory stimuli causing release of neutrophil proteins. Concentrations of neutrophil lactoferrin and a 37-kd cationic bactericidal protein (CAP 37) were measured in 47 MEEs collected from 27 children at the time of tympanostomy tube placement. Antigens of Streptococcus pneumoniae were detected by latex particle agglutination and those of Haemophilus influenzae by dot-blot assay. Bacterial antigens were detectable in 24 (51%) of MEEs: S pneumoniae in 10 (21%), H influenzae in 12 (26%), and both antigens in 2 (4%). Concentrations of lactoferrin and CAP 37 in H influenzae antigen-positive MEEs were significantly higher than in either S pneumoniae antigen-positive or antigen-negative MEEs. We conclude that H influenzae antigen causes a greater middle-ear inflammatory response, as judged by neutrophil products, than does S pneumoniae antigen. PMID- 2306353 TI - Eye movement analysis system using computerized image recognition. AB - A new technique for an eye movement analysis system utilizing infrared video recording and a computerized image recognition method is presented. The system consists of an infrared lighting apparatus, a very small infrared video charge coupled device camera, a video tape recorder, an analogue-digital converter, and microcomputers. This system makes it possible to simultaneously analyze the slow phase velocity quantitatively not only of the horizontal and vertical but also of the rotatory components of the energy-induced nystagmus. The maximum slow-phase velocity of the rotatory component of energy-induced nystagmus was found to be 4.1 degrees per second on an average in this study. PMID- 2306354 TI - A survey of otologic training in US residency programs. AB - Otologic cases are dwindling in numbers, jeopardizing the clinical training of our residents. A survey was performed to determine the magnitude of the problem facing our training programs. Seventy-three of 79 questionnaires distributed were returned. Results of the survey indicate that facial nerve decompression, exostosis repair, and stapedectomy were, on the average, infrequently performed by residents. Training for these seldom-performed procedures consists of temporal bone laboratory experience, close operative supervision, and the use of private patients for resident training. The majority (84%) of respondents did not feel that fellowship training was required to perform otologic surgery on graduation or that it should be required for obtaining hospital privileges in seldom performed cases. Approximately three quarters (76%) of the program directors consider the training of seldom-performed procedures to be a moderate-to-serious problem facing otologic training today. PMID- 2306355 TI - Three-dimensional anatomy of the human endolymphatic sac. AB - Computerized and graphic three-dimensional reconstruction of a human endolymphatic duct and sac (ES) showed the ES to be a fusiform and flattened structure with marked tubularity, especially in the extraosseous region. The specimen was 18.2 mm long. It measured 60 X 200 microns at the isthmus portion of the endolymphatic duct and 200 X 7000 microns at the broadest part of the ES. The volume of the endolymphatic duct was 0.03 mm3 and of the ES, 1.85 mm3. The extraosseous ES volume represented more than two thirds of the total ES volume. PMID- 2306356 TI - Fish-odor syndrome presenting as dysosmia. AB - We describe a patient who had perceived an unpleasant odor or taste for at least 20 years. Several other physicians had unsuccessfully treated her for infections, mucus membrane dryness and inflammation, chronic tonsillitis, and psychiatric disorders. Her workup at the State University of New York Health Science Center at Syracuse Olfactory Referral Center included a thorough history, examinations (including endoscopic studies of her nose, pharynx, and lungs), roentgenograms, taste testing, olfactory testing, and selective anesthesia of her chemosensory areas. The perception occurred only during exhalation, and appeared to be binasal. These findings, together with her morning mucus sample having a strong fishlike odor, prompted us to suspect a metabolic problem. Further testing at the Monell-Jefferson Chemosensory Clinical Research Center, Philadelphia, Pa, confirmed that she had trimethylaminuria. It is important to consider this and other treatable conditions when evaluating individuals with olfactory complaints. PMID- 2306357 TI - Neck dissection injury of a brachial plexus anatomical variant. AB - We describe an unusual brachial plexus anatomical variant that renders it vulnerable to injury in radical or modified neck dissection. It is represented by a looping redundant course of the most cephalad cervical division contribution to the brachial plexus. Unless recognized during development of the inferior surgical plane by blunt dissection techniques, injury to this portion of the brachial plexus may occur. An awareness of this infrequent variation in brachial plexus anatomy should be maintained. PMID- 2306358 TI - A technique to treat wrestler's auricular hematoma. PMID- 2306359 TI - Adenoidectomy for secretory otitis media. PMID- 2306360 TI - Pathologic quiz case 2. Mesenchymal chondrosarcoma. PMID- 2306361 TI - Pathologic quiz case 1. Benign schwannoma of the parapharyngeal space. PMID- 2306362 TI - A comprehensive survey of graduate education and training in hazardous waste management. AB - The United States Department of Health and Human Services through Wayne State University (WSU) has completed a study of hazardous waste education and training in the United States. The study documents university course work and degrees as well as non-degree continuing education short courses. Major portions of the study are based on a WSU sponsored survey in which 1469 four-year degree granting institutions were contacted. Of the 732 institutions responding, 113 were identified as offering course work of some kind in hazardous waste. Information on 499 distinct non-degree short courses was also gathered and evaluated. The purpose, methodology and results of the study are summarized in this article. PMID- 2306363 TI - Determination of organic contaminants in residential indoor air using an adsorption-thermal desorption technique. AB - This field study evaluated the ability of a multi-sorbent sampling tube/thermal desorption technique to identify and to provide quantitative data on volatile organic contaminants in indoor air. Air samples, from 12 Canadian homes, were collected on multilayer sorbent cartridges and analyzed using Adsorption/Thermal Desorption coupled with Gas Chromatography/Mass Spectrometry. The study included the identification and quantitation of 23 target compounds. Analysis of sorbent tubes fortified with these target compounds indicated that recoveries were greater than 70 percent and the precision was usually better than 15 percent. These organic compounds were found to be stable on the sorbent tubes for at least seven days. With some exceptions, the target compounds were usually detected at 1 to 10 micrograms/m3 in indoor air samples; other organics identified qualitatively were saturated hydrocarbons, unsaturated hydrocarbons, cyclic hydrocarbons, substituted aromatics, oxygenates, some halogenates and cyclic species such as camphenes/pinenes and carenes. PMID- 2306364 TI - Impact of heating and air conditioning system operation and leakage on ventilation and intercompartment transport: studies in unoccupied and occupied Tennessee Valley homes. AB - Forced-air heating and air conditioning (HAC) systems caused an average and maximum increase in air infiltration rates of 1.8- and 4.3-fold, respectively, during brief whole-house studies of tracer gas decay in 39 occupied houses. An average increase in air infiltration rate of 0.33 +/- 0.37 h-1 corresponded to an incremental air leak of 240 m3/h, based on approximate house volume. More detailed tracer gas decay studies were performed in basement, kitchen and bedroom locations of six homes with low air infiltration rates (i.e., less than 0.25 h 1). The HAC mixed the indoor air efficiently between measurement sites. HAC operation also caused 1.1- to 3.6-fold increases in air infiltration rates, corresponding to absolute increases of 0.02 to 0.1 h-1. In an unoccupied research house, three-fold increases in average air infiltration rate with HAC operation (i.e., from 0.13 to 0.36 h-1) were reduced to two-fold (i.e., from 0.10 to 0.18 h 1) by sealing the external HAC unit and crawlspace ductwork system. This sealing also resulted in a 30 percent reduction in crawlspace-to-indoor transport rates with the HAC turned on. Blower door tests indicated a less than 20 percent reduction in house leakage area. PMID- 2306365 TI - Different biological activities in conditioned media control the expression of a variety of neuropeptides in cultured sympathetic neurons. AB - An intriguing question regarding neuronal development is how neurons choose which neurotransmitter and/or peptide to express among over 40 candidates. We find that heart cell conditioned medium (CM) induces a number of neuropeptides and/or their precursor mRNAs, as well as acetylcholine, in cultured rat sympathetic neurons: substance P, somatostatin, vasoactive intestinal polypeptide, enkephalin derivatives, and cholecystokinin, but not neuropeptide Y. Different patterns of peptide induction were observed for CMs from primary cultures of heart, gut, and skin. Acetylcholine and substance P were induced most effectively by serum-free heart cell CM; enkephalin derivatives were induced most effectively by skin cell CM; and somatostatin and vasoactive intestinal polypeptide were induced equally well by all of the CMs. These observations suggest the possibility that many distinct, diffusible factors can influence the choice of transmitter and/or peptide phenotype in developing neurons. PMID- 2306366 TI - Single gene encodes glycophospholipid-anchored and asymmetric acetylcholinesterase forms: alternative coding exons contain inverted repeat sequences. AB - Polymorphic forms of acetylcholinesterase are tethered extracellularly either as dimers membrane-anchored by a glycophospholipid or as catalytic subunits disulfidelinked to a collagen tail that associates with the basal lamina. Genomic clones of acetylcholinesterase from T. californica revealed that individual enzyme forms are encoded within a single gene that yields multiple mRNAs. Each enzyme form is encoded in three exons: the first two exons, bases -22 to 1502 and 1503 to 1669, encode sequence common to both forms, while alternative third exons encode a hydrophobic C-terminal region, to which a glycophospholipid is added upon processing, and a nonprocessed C-terminus, yielding a catalytic subunit that disulfide-links with a collagen-like structural unit. The 3' untranslated region of each alternative exon contains tandem repeat sequences that are inverted with respect to the other exon. This may either dictate alternative exon usage by formation of cis stem-loops or affect the abundance of translatable mRNA by trans hybridization between the alternative spliced mRNA species. PMID- 2306367 TI - Pulmonary bombesin and calcitonin in hamsters during exposure to hyperoxia and diethylnitrosamine. AB - Combined exposure of hamsters to 60% hyperoxia and the carcinogen diethylnitrosamine for 6 wk resulted in the development of lung tumors. This was associated with progressive loss of body weight as well as increases in the pulmonary-associated peptides, mammalian bombesin (MB) and immunoreactive calcitonin (iCT). After 3 wk of exposure, multiple bronchial epithelial hyperplastic foci were noted, along with increased lung levels of MB and iCT as well as increased serum levels of MB. At this time, immunocytochemistry revealed the presence of MB and iCT within hyperplastic pulmonary neuroendocrine (PNE) cells. In addition, the localization of MB to alveolar type II cells was noted, along with the presence of lamellar bodies and secretion granules in these cells on electron microscopy. After 6 wk of exposure, distinctive microscopic pulmonary tumorlets were seen. These tumorlets were associated with a marked increase in lung and serum MB, and to a lesser extent lung and serum iCT. At this time, MB and iCT were localized exclusively to these abnormal PNE cell sites. These results, which may have relevance in humans, suggest that endogenous peptides may be important components in the process of development of neuroendocrine cancer. PMID- 2306368 TI - Human tracheobronchial submucosal gland cells in culture. AB - Cellular mechanisms regulating airway secretion, secretory products of individual airway cell types, and control of airway cell growth and differentiation are poorly understood. In order to aid studies of these questions, we have established a system for culturing human tracheobronchial submucosal gland cells. Gland acini were isolated by enzymatic disaggregation from submucosal tissue obtained postmortem from patients without pulmonary diseases and from patients with cystic fibrosis. In culture, acini attached to a collagen substratum, and gland cells proliferated and formed confluent monolayers which were homogeneous by phase microscopy. In contrast to cells of freshly disaggregated acini which expressed either serous or mucous gland cell secretory antigens, in culture virtually all cells (greater than or equal to 95%) concurrently expressed both antigens as assessed by immunocytochemical staining with serous and mucous cell specific antibodies. Similarly, electron microscopy revealed cells with serous- or mucous-type secretory granules, and cells containing both types of granules. Cultures incorporated 35S into high (greater than 10(6) D) and lower (greater than 700 kD; 150 kD) molecular weight molecules. Cholinergic and adrenergic agonists increased release of radio-labeled secretions. These findings demonstrate that human tracheal gland cells in culture retain immunocytochemical, ultrastructural, and functional features of both differentiated serous and mucous gland cells. This culture system will be useful for studying the biology and pathology of human tracheobronchial submucosal gland cells. PMID- 2306369 TI - Cell kinetics of normal adult hamster bronchial epithelium in the steady state. AB - To establish the progenitor role of bronchial epithelial cells in the steady state, we undertook a quantitative autoradiographic study in normal hamsters. Groups of 7 hamsters were killed 1 h and 1, 2, 3, 4, 7, and 14 d after an intraperitoneal injection of [3H]thymidine (2 microCi/g body wt). Autoradiograms were prepared from 861 Epon sections, 2 microns thick, of left intrapulmonary hilar bronchi. Epithelial cells were classified into 1 of 7 categories: basal-1 (B1) and basal-2 (B2), depending on nuclear height; secretory cells denoted as S1 with zero to 4 granules, S2 with 5 or more granules with intervening cytoplasm, and S3 with abundant granules completely filling the cytoplasm; ciliated (C); and indeterminate (IN). Mean silver grain counts decreased significantly over time only for B1 cells (P less than 0.05), with a cell cycle time of 20.6 d and a DNA synthetic time of 7.5 h. Labeled cells, 1 h after thymidine injection, comprised 30.5% S1, 27.8% B1, 22.8% B2, 6.8% IN, 6.4% S2, 5.7% C, and 0% S3 cells. Labeling indices of individual cell categories (LIc), at 1 h after labeling, were highest for B1 followed by B2 cells, reflecting their proliferative intensity. Labeling index of all epithelial cells combined did not change with time, indicating that there was no major cell death or label dilution. The LIc decreased significantly over time only for B1 and B2 cells (P less than 0.001 and P less than 0.002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306370 TI - Pulmonary surfactant protein A enhances the host-defense mechanism of rat alveolar macrophages. AB - The effects of surfactant, surfactant lipids, and surfactant protein A (SP-A) on the surface phagocytosis of [3H]thymidine-labeled Staphylococcus aureus (SAE) by rat alveolar macrophages were studied. Alveolar macrophages only ingest SAE when the bacteria are opsonized with rat serum prior to incubation with alveolar macrophages. Preincubation or "opsonization" of the bacteria with surfactant did not result in phagocytosis by the macrophages. However, preincubation of the macrophages with surfactant increased the phagocytosis of rat serum-opsonized bacteria by approximately 70% when compared to the control macrophages. The factor present in surfactant causing the stimulation of the phagocytosis is probably SP-A. Preincubation of macrophages with human SP-A enhanced the phagocytosis to the same extent as whole surfactant, whereas preincubation with surfactant lipids had no effect on the phagocytosis. The SP-A-induced enhancement of the phagocytosis is time, temperature, and concentration dependent. Phagocytosis of opsonized SAE by alveolar macrophages was maximal after 15 min of incubation and at an SP-A concentration of 1 micrograms/ml. No phagocytosis occurred at 0 degrees C. In addition, whole surfactant and SP-A induce a lucigenin-dependent chemiluminescence response in alveolar macrophages. The chemiluminescence response is initiated after 15 min of incubation and reaches a maximum after 30 min. The concentration of SP-A needed for an optimal response is in the same order of magnitude as the concentration needed for maximal enhancement of the phagocytosis of SAE by alveolar macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306371 TI - Characterization of guinea pig tracheal epithelial cells maintained in biphasic organotypic culture: cellular composition and biochemical analysis of released glycoconjugates. AB - An air-liquid interface (biphasic) primary culture system in which guinea pig tracheal epithelial cells maintain morphologic characteristics of differentiated epithelium has been developed in this laboratory. In this report, we compared quantitatively cell populations of 8-day cultures to those of epithelial mucosa in intact trachea. In addition, high molecular weight glycoconjugates released by the cultured cells were isolated and characterized. Quantitative morphometric analysis revealed similar volume densities of ciliated, secretory, basal, and "other" cells in cultures and in intact tracheal surface epithelium, although the cultures tended to have smaller cells and contained fewer basal cells. High molecular weight glycoconjugates released apically by cell cultures and excluded from Sepharose CL-4B columns contained approximately 5% hyaluronic acid but undetectable amounts of other proteoglycans, such as chondroitin sulfate, heparan sulfate, and dermatan sulfate. The hyaluronidase-resistant glycoconjugates exhibited a peak buoyant density at 1.49 g/ml on cesium chloride density gradient centrifugation and were shown to contain mucin-type carbohydrate to peptide linkages (i.e., GalNAc to ser/thr) and an amino acid composition typical of respiratory mucins. The results indicate that this organotypic cell culture system mimics quite closely morphology of mucosal epithelium in intact airways and that the cells release high molecular weight glycoconjugates with biochemical properties of mucin-type glycoproteins. Thus, this in vitro system appears well suited for studies of mucin secretion and other functions of respiratory epithelial cells. PMID- 2306372 TI - Effect of alpha-1-proteinase inhibitor on neutrophil chemotaxis. AB - Factors that modulate neutrophil migration into the lung are poorly understood. However, there is evidence that neutrophil activation by formylmethionylleucylphenylalanine (FMLP) depends upon a surface proteinase with chymotrypsin-like activity. This suggests that chymotrypsin inhibitors such as alpha-1-proteinase inhibitor (alpha 1PI) could modify neutrophil migration in response to FMLP. We have studied neutrophil chemotaxis using the multiple blind well assay system. This article presents evidence that alpha 1PI is an inhibitor of neutrophil migration in response to FMLP. The effect is related to the inhibitory function of the protein. Alpha-1-antichymotrypsin is more potent than alpha 1PI as an inhibitor of this movement, whereas antileukoprotease is less potent. The results suggest that a cell membrane-bound serine proteinase (perhaps cathepsin G) is necessary for the enhancement of cell movement after receptor binding of FMLP. Oxidized alpha 1PI or a 4,000-D peptide cleaved from alpha 1PI by porcine pancreatic elastase or human neutrophil elastase are capable of enhancing cell motility. The results suggest that alpha 1PI may play a role in cell migration into the lung during acute inflammatory process. PMID- 2306373 TI - Uptake of muramyl dipeptide fluorescent congeners by normal rabbit bronchoalveolar lavage cells: a study using flow cytometry. AB - Muramyl dipeptide (MDP) is the minimal adjuvant-active structure of mycobacterial cell walls and is known to activate monocytes/macrophages, but mechanisms involved with uptake and activation of these cells have not been completely defined. Earlier studies addressing uptake of MDP and the question of receptors have utilized radioligands and murine peritoneal macrophages. We used fluorescent congeners of MDP and flow cytometry to explore kinetics and specificity of uptake by bronchoalveolar cells of normal rabbits. Both washed cells and cell suspensions from which the fluorescent congeners were not washed were used, and incubation was carried out primarily at 4 degrees C. Fluorescence microscopy consistently revealed intracellular but no visible membrane fluorescence of alveolar macrophages. Uptake was dose dependent but was not saturable up to concentration limits of fluoresceinated muramyl tripeptide (MTP-FITC) imposed by the system, and was partially inhibited by excess unlabeled MDP, consistent with specific inhibition. Alveolar macrophages, but not lymphocytes, demonstrated specific uptake at 4 degrees C, with rapid on- and off-times. Uptake was enhanced 7-fold at 37 degrees C. Uptake was greater by larger, more granular macrophages than by smaller, less granular macrophages, but no difference in uptake was found when cells of similar size but different densities were compared. The exact mechanism of the rapid uptake at 4 degrees C is uncertain but appears to be competed for by unlabeled MDP. PMID- 2306374 TI - Effect of a reconstituted basement membrane on expression of surfactant apoproteins in cultured adult rat alveolar type II cells. AB - Pulmonary surfactant, which is composed of phospholipids and three lung-specific apoproteins, is synthesized and secreted by alveolar type II cells. Previous work from this laboratory (Biochim. Biophys. Acta 1987; 931:143-156) has shown that cell-extracellular matrix interactions and cuboidal cell shape affect both the ultrastructural appearance and pattern of phospholipids synthesized by cultured rat type II cells. In the present study, we have examined the effects of cell matrix interactions and cell shape on the ability of adult rat type II cells to express the surfactant apoproteins in culture. Isolated adult rat type II cells were cultured for 2, 4, and 8 days on either tissue culture plastic, on an extract of the Engelbreth-Holm-Swarm (EHS) tumor, or on laminin-coated plastic dishes. Expression of surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) was evaluated by Northern analysis using specific rat cDNA probes for these mRNAs. SP A content was determined by enzyme-linked immunosorbent assay using a polyclonal antibody raised against rat SP-A purified from lavage. Type II cells cultured on plastic dishes assumed an attenuated morphology soon after being placed in culture. Except for an occasional positive signal on day 2 of culture, these cells were uniformly negative for the presence of mRNA for SP-A, SP-B, or SP-C. Type II cells cultured on plastic did not contain SP-A. In contrast, type II cells cultured on EHS gels formed three-dimensional aggregates on the surface of the substratum; these aggregates were composed of polarized cells that had their apical surfaces directed inward. Type II cells cultured on this substratum showed a positive signal for mRNA for all three surfactant proteins; the abundance of these mRNAs, however, was significantly below that seen in freshly isolated type II cells. While the abundance of mRNA for SP-A and SP-B steadily increased with time in culture under these conditions, the abundance of SP-C mRNA decreased, suggesting that SP-C is regulated independently of SP-A and SP-B. These cultures were also positive for SP-A content, which increased with increasing time in culture. Type II cells cultured on laminin-coated dishes initially spread more slowly across the culture surface than cells on plastic, but were extremely attenuated by day 8 in culture. These cells contained neither SP-A, nor mRNA for any of the three surfactant proteins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2306375 TI - A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation. AB - Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306376 TI - Clinical evaluation of the Bjork-Shiley disc valve in the tricuspid position. Long-term results. AB - Between 1971 and 1981, 1210 Bjork-Shiley prostheses were implanted. Of these, 79 were in the tricuspid position, comprising 30 triple valve replacements, 46 mitral plus tricuspid, and 3 isolated tricuspid replacements. The ages ranged from 10-55 years (mean 45 years). Sixty-three patients (80%) were in NYHA grades III or IV preoperatively. Thirteen patients died in hospital after surgery (16.5%). The 66 survivors have been followed for up to 16 years (mean 7.5 years). There have been 37 late deaths (7.5 per patient year). Twelve were valve-related: 4 tricuspid complications, 4 mitral complications, 2 prosthetic endocarditis, 1 aortic leak and 1 anticoagulant-related bleed. Twenty-one late deaths were not valve-related, and 4 causes of death are unknown. Expressed actuarially, survival at 5 years was 68%, and at 10 years, 49.4% +/- 12%. Freedom from valve-related death at 10 years was 80.7% +/- 7%. At last follow-up, 90% of the survivors were in NYHA class 1 or 2 with only modest signs of venous hypertension. The commonest life-threatening complication was obstruction of the tricuspid prosthesis by tissue ingrowth. This occurred in 7 patients (1.4% per patient year) 4 were re operated upon and survived, 3 died. Doppler echocardiography has been carried out on 27 survivors of whom 5 had abnormal pressure-half times but only 3 of these were symptomatic. This series shows that function of the standard disc Bjork Shiley prosthesis in the tricuspid position compares favourably with other prostheses. The problem of tissue ingrowth can be diagnosed by echo Doppler and reoperation successfully carried out. PMID- 2306377 TI - Therapeutic use of right atrial pressures early after the Fontan operation. AB - In 334 patients undergoing the Fontan operation, the right atrial pressure was 16 +/- 36 mm Hg (mean value +/- SD) 3 h postoperatively, and was on average higher in those who died or had a takedown of the operation than in those who did not (P = 0.0001). Twenty-four hours after operation, the right atrial pressure was 18 +/ 5.5 mm Hg, was higher in those who died or had a takedown than in those who did not (P less than 0.0001); and in those who died or had takedown it was 23.5 +/- 1.66 mm Hg and higher than at 3 h postoperatively (18.7 +/- 0.52). The left atrial pressure 3 h postoperatively was 9 +/- 3.6 mm Hg, and on average was higher in the patients who died or had a Fontan takedown than in those who did not. The continuous relation between right atrial pressure and the probability of death or takedown during the first 24 postoperative hours was such as to recommend consideration of takedown whenever the right atrial pressure reaches 22 mm Hg, and when higher, the recommendation is made with greater urgency. PMID- 2306378 TI - Non-invasive assessment of right and left ventricular volumes 11 to 24 years after corrective surgery on patients with tetralogy of Fallot. AB - Patients who had corrective surgery for tetralogy of Fallot using a transannular right ventricular outflow tract (TRVOT) patch showed a higher risk of post operative mortality and reoperation in the long-term follow-up. A total of 642 patients were operated upon for tetralogy of Fallot between 1952 and 1982. Twenty six patients who survived for more than 10 years were selected for this study. Fifteen randomly selected patients (group 1) without outflow tract patch were compared with 11 patients (group 2) where a transannular right ventricular outflow patch had been used. Right and left ventricular volumes were assessed using combined first-pass and equilibrium radionuclide ventriculography. After administration of 25 mCi of 99mTc-pertechnetate, data were acquired with a gamma camera with a large viewing field and the patient at rest and during exercise. The patients in group 1 were able to manage a workload of 65 +/- 24 W on the bicycle ergometer while the patients in group 2 could only reach a mean maximum of 34 +/- 12 W. Right ventricular end-diastolic volume (RV-EDV) at rest was 198 +/- 67 ml in group 1 and 224 +/- 69 ml in group 2. During exercise, RV-EDV was increased to 218 +/- 75 ml in group 1 (P less than 0.01) and to 246 +/- 79 ml in group 2. Right ventricular end-systolic volumes did not change significantly during exercise. In group 1, the left ventricular (LV) volumes were comparable to the normal; in group 2, LV-EDV was diminished at rest and during the stress test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306379 TI - Reoperation for recurrent angina after aortocoronary bypass surgery. AB - One hundred reoperations were performed on 93 patients of a total of 2287 patients who underwent initial coronary artery bypass surgery (CABG) between September 1972 and August 1988. The mean age of the 84 males and 9 females was 55.5 years (range 31-75 years). All patients prior to reoperation had severe angina and were judged to be in NYHA class III or class IV. Late graft failure alone or in combination with progressive atherosclerosis accounted for more than 60% of the cases requiring reoperation. The early mortality for reoperation was 1% compared with 1.4% for initial CABG. Perioperative myocardial infarction was recorded as a complication in 3.2% of cases at initial operation compared with 1% at reoperation. Symptomatic improvement occurred in 89.1% of cases after reoperation and almost 60% became entirely asymptomatic (mean follow-up interval 17 months). PMID- 2306380 TI - Amelioration of reperfusion injury following hypothermic, ischemic cardioplegia in isolated, infarcted rat hearts. AB - The left coronary artery was ligated and myocardial infarction developed in 28 rats. Three weeks later, the hearts were excised and mounted in an apparatus for perfusion of non-working isolated hearts (Langendorff). Hypothermic (15 degrees C), ischemic cardioplegia was induced for either 2 or 3 1/2 h followed by reperfusion for 45 min. Half of the hearts were reperfused with an initially gradual rise in temperature and pressure of the perfusion fluid, whereas the other half was reperfused directly with the perfusate at 37 degrees C and 100 cm H2O pressure. The hearts were examined by transmission electron microscopy and randomized for stereological analysis based on point counting on electron micrographs. Cardioplegia of 2 h duration was tolerated better than cardioplegia for 3 1/2 h (interstitial edema; P = 0.03, fraction of altered mitochondria; P = 0.001). Particularly in the hearts undergoing the longest cardioplegia, myocardial injury was less severe following a gentle reperfusion as compared with those exposed to the clinically common abrupt technique (fraction of mitochondria in the myocyte; P = 0.03, fraction of altered mitochondria; P = 0.008). In the interstitium, the luminal area of capillaries was significantly increased and the endothelial swelling less pronounced in the groups undergoing the gentle reperfusion technique, (luminal/endothelial fraction; P = 0.01). The study shows that previously infarcted hearts are susceptible to ischemic damage even after 2 h of regular hypothermic, ischemic cardioplegia and that a gentle reperfusion technique significantly ameliorates reperfusion injury. PMID- 2306382 TI - Surgical treatment of bilateral chylothorax due to benign lymphangioma of the thoracic duct. AB - We present a female patient in whom after an 8-year history of recurrent bilateral pleural effusions, a benign lymphangioma of the thoracic duct was diagnosed and successfully treated by ligation of the duct, resection of the tumour and simultaneous decortication of the right pleural space and lung. This observation supports surgical intervention in this condition even in patients of advanced age. PMID- 2306381 TI - Surgical repair and postoperative course of an infant with infracardiac total anomalous pulmonary venous connection, cor triatriatum sinistrum and transposition of the great arteries. AB - The combination of a d-transposition of the great arteries, cor triatriatum sinistrum and a total anomalous pulmonary venous connection of the infracardiac type is a very rare condition. Up to now, one surgical repair in an adolescent with transposed great arteries and total anomalous pulmonary venous drainage of the supracardiac type has been reported. In this paper, an infant with the above mentioned cardiovascular malformation is presented. The common pulmonary vein drained into the inferior vena cava and was obstructed. There were arborisation abnormalities in both lungs with mild pulmonary hypertension. The infant has been successfully operated upon at the age of 6 months and a weight of 4.5 kg. The membrane within the left atrium was resected, the common pulmonary vein was anastomosed to the left atrium and a Mustard procedure was performed. During the first 6 postoperative weeks, the infant had problems with adaptation. There was both a transient ballooning of the Mustard patch with significant obstruction of the pulmonary venous drainage and a delayed pulmonary recovery. Two months later, the patch was straightened and the child could be discharged from hospital. After 12 months, the child died from an infection of the airways. PMID- 2306383 TI - The use of an implantable left ventricular assist device following irreversible ventricular fibrillation secondary to massive myocardial infarction. AB - A TCI1 rough surface left ventricular assist device (LVAD) was implanted in a 47 year-old man who had sustained a recent massive myocardial infarction complicated by ventricular failure which remained unresponsive to intra-aortic balloon pump therapy and which was further complicated by irreversible ventricular fibrillation. Following implantation of the device and while awaiting a suitable donor organ for transplantation, further extension of the previous infarct resulted in left ventricular rupture and massive haemorrhage which led to his death. We report the successful use of the device in providing haemodynamic support, but caution against inordinate delay in bridging to transplantation patients who are at risk of extension of infarction. PMID- 2306384 TI - Myasthenia gravis: effect of thymectomy in 425 patients. A 15-year experience. AB - We report 425 myasthenic patients who underwent thymectomy during the last 15 years. The authors analyse the results of thymectomy in separate groups, including thymomas (12.7%), childhood myasthenia (9.4%) and combined cases (12.4%). They evaluate the results according to the Disability Status Scale based on a points system. Three series were evaluated: patients operated upon between 1972-1977, 1977-1982 and 1982-1987. Although the results in all three series were good, there has been steady improvement over the years. Childhood myasthenia gravis gave the best results but thymectomy was beneficial in the combined (immunological) group, in long-lasting myasthenia and in thymomas. Factors influencing the results of thymectomy were patients' age, time interval between onset of disease and thymectomy, resistence to therapy and thymic tumour. Thymic activity as reflected in germinal centres can also influence the results: the more active the thymus, the better the results. PMID- 2306385 TI - Roll up your sleeves, spit in your hands--there is still much to do in dialysis of the elderly. PMID- 2306386 TI - Dialysis-related amyloidosis during peritoneal dialysis. AB - Patients treated with long-term hemodialysis may develop carpal tunnel syndrome, cystic bone lesions, and/or an arthropathy. This syndrome has been called hemodialysis-related amyloidosis (HRA) and appears to be the result of the accumulation of polymerized Beta-2 microglobulin (B2M). The risk to patients treated with peritoneal dialysis is unknown. Diphosphonate scans have been advocated as a useful noninvasive test for HRA. The authors report a well documented case of HRA established during hemodialysis and progressing during peritoneal dialysis. In addition, this patient's HRA was not identified by a diphosphonate scan. This is the second well-documented case of HRA associated with peritoneal dialysis. PMID- 2306387 TI - Brain edema and the blood brain barrier in galactosamine-induced fulminant hepatic failure rats. An animal model for evaluation of liver support systems. AB - Rats with galactosamine-induced fulminant hepatic failure (FHF) have been a popular animal model for the evaluation of liver support systems. Because development of brain edema is a major and frequent complication during FHF, it was studied for this report. The degree of hepatocyte necrosis closely paralleled the severity of coma. Abnormalities in the orientation of hepatocellular organelles were evident as early as grade I hepatic coma, 24 hr after galactosamine-induced liver damage. Galactosamine caused a characteristic pattern of hepatocyte necrosis such that the endoplasmic reticulum completely surrounded the nucleus to cause karyolysis and subsequent cell death. Quantitative measurements of brain water content revealed evidence of brain edema with increasing severity of coma. Brain edema resulted in a greater than 4% swelling of the brain during this period. Light microscopy showed increasing cerebral and cerebellar edema during progressive stages of FHF. Electron microscopy studies revealed evidence of progressive cerebral edema, particularly in the perivascular region of cerebral capillaries. Marked swelling of perivascular astrocytes was evident as early as 24 hr after galactosamine-induced FHF when the animals were in Grade I hepatic coma. Abnormal swelling and distortion of astroglia, including its subcellular organelles, and the presence of cytoplasmic vacuoles, was clearly evident during the deeper stages of hepatic coma (Grades II-IV). Trypan blue dye infusion studies revealed evidence of extensive blood-brain barrier (BBB) breakdown beginning in Grade III coma. PMID- 2306388 TI - New investigations of a pulsatile impeller blood pump. AB - For circulatory assist devices and total artificial heart systems, impeller blood pumps with small total volumes would be fully implantable. One of the main obstacles, however, is generation of a pulsatile flow. The simplest way to overcome this problem is by changing the pump's revolutions per minute (rpm) periodically, but this often results in severe hemolysis. After theoretic analysis, two in vitro models of impeller blood pumps have been devised, producing pulsatile flow with constant rpm. In the first model, the impeller oscillates in an axial direction during constant rotation. The pump is driven by a DC motor (rotating) and a pneumatic device (oscillating). The form of the pulsatile pressure wave depends upon duration and amplitude of the oscillation. With 40% systolic duration and a 50 mm axial amplitude, a 70 mmHg pressure amplitude (170/100) is achieved with a semiphysiologic shape at a flow of 12 L/min. The second model produces a pulsatile flow by differing the gaps between impeller and cap on the inlet pipe. Both the cap and impeller have cone-shaped heads, and impeller oscillations of 1.5-2 mm, for example, results in a pressure pulse of 40 mmHg (150-110) at 7 L/min flow. Results of theoretic analyses have shown that both models create less turbulence in the impeller, with a consequent reduction in blood cell damage as compared to pumps with changing rpms. PMID- 2306389 TI - Dialyzer urea and creatinine clearances are not significantly altered in erythropoietin treated maintenance hemodialysis patients. AB - Recombinant human erythropoietin (r-HuEPO) was given to 51 maintenance hemodialysis patients in an attempt to correct the anemia of uremia. A subset of eight randomly chosen stable patients (four men and four women, mean age 42.3 years) had in vivo urea and creatinine dialyzer clearances measured before and after their hematocrits were increased by r-HuEPO treatment. The same dialyzer was used in both the pre-r-HuEPO and post-r-HuEPO studies. Dialyzer creatinine (Ccr) and urea (Ucr) clearances were measured at a blood flow of 300 ml/min 1 hour after the initiation of dialysis. The mean hematocrit of the group of 51 patients increased from 19% (range, 14-28%) to 33% (range, 21-27%). The mean hematocrit of the eight patients in whom the clearance studies were done was 19% before r-HuEPO and 35% after. Mean creatinine and urea clearances for the eight subjects at the lower hematocrit were 143 and 190 ml/min, respectively. After the increase in hematocrit, the mean creatinine and urea clearances were slightly lower at 132 and 166 ml/min, respectively. No patient had a rise in predialysis serum potassium, creatinine, or blood urea nitrogen. The authors concluded that the magnitude of changes in creatinine and urea clearances secondary to a r-HuEPO stimulated rise in hematocrit will be small and will not necessitate increases in dialysis time. PMID- 2306390 TI - Effects of moderate hyperkalemia on the sinus node. Evaluation in anesthetized dogs. AB - From clinical experience that sinus node dysfunction was observed on the day of hemodialysis and that the arrhythmias were corrected immediately after initiation of hemodialytic therapy, the effect of moderate hyperkalemia on sinus node function was experimentally evaluated. When the serum potassium level was elevated to 5.78 +/- 0.96 mEq/L, sinus node recovery time evaluated by the overdrive suppression test was significantly prolonged (p less than 0.05). Atrial refractory periods also increased (p less than 0.01 or p less than 0.02). Atrial repetitive response was observed in some dogs after the induction of moderate hyperkalemia by premature stimuli. Although the study was performed in anesthetized dogs, moderate hyperkalemia might depress sinus node function in awake humans. PMID- 2306391 TI - Combined registry for the clinical use of mechanical ventricular assist devices. Postcardiotomy cardiogenic shock. PMID- 2306392 TI - Oral cancer and precancer: establishing a diagnosis. AB - In this article in the Oral Cancer series, consideration is given to the various factors that should be taken into account in deciding upon, and carrying out, a biopsy of potentially malignant lesions of the oral mucosa. The ways in which a biopsy specimen may be spoiled by incorrect handling are described, and advice is provided on the procedures to be followed when submitting such material to a pathology laboratory. Other methods of sampling tissues for diagnostic purposes are briefly reviewed, followed by an account of the main pathological features of oral cancer and precancer. PMID- 2306393 TI - Dental care for elderly people by general dental practitioners. AB - In Salford, the care and facilities for elderly people provided by general dental practitioners in practices having three or more dentists were compared with those given in smaller practices. Accessibility and size of dental practice were significantly related, with larger practices being more accessible to elderly and disabled people than smaller ones. A domiciliary service was given by all dentists, regardless of size of the practice. Forty-three per cent of dentists in the larger but none in the smaller practices recalled full denture patients. Eighty-seven per cent of dentists in the larger practices, compared with 53% of those in small ones, gave correct answers to seven or more of 14 questions about the elderly. Attitudes towards the elderly were measured using a seven-point scale: the more favourable the attitude, the higher the score. The mean score for dentists in large practices was 5.13, which was significantly greater than the mean score of 4.16 for those in small practices (P less than 0.001). PMID- 2306394 TI - Primary hyperparathyroidism presenting as a massive maxillary swelling. AB - A patient with primary hyperparathyroidism is reported, in which the sole presenting feature was an orofacial swelling. Untreated, the disease is life threatening and its early recognition will reduce the risk of morbidity. Recent figures suggest that the incidence of the condition tends to be underestimated. PMID- 2306395 TI - Sensitivity reaction to the cinnamonaldehyde component of toothpaste. AB - Sixteen patients developed a variety of oral lesions following a change in the toothpaste they used. Mucosal biopsy demonstrated features consistent with application of a topical medicament and patch testing, towards the constituents of the toothpastes, indicated the flavouring agent cinnamonaldehyde as being the likely responsible agent. Avoidance of the implicated toothpastes resulted in a considerable improvement in clinical signs and symptoms, whereas rechallenge in ten patients resulted in recurrence of symptoms in eight patients. It is concluded that sensitivity to the cinnamonaldehyde constituent of certain toothpastes, although uncommon, should be considered as a possible aetiological factor in patients presenting with non-specific oral changes. PMID- 2306396 TI - The capitation study. 1. Does capitation encourage "supervised neglect'? AB - Four matched pairs of geographically and socially contrasting areas of Britain were randomly allocated within pairs to either a capitation or fee-for-service payment system for the dental care of children in a 3-year clinical trial. Measurements were made on the dental health of randomly selected 5-6 and 14-15 year-old patients and the views of their parents elicited. Patterns of treatment were also gained from the clinical records of randomly selected patients. In addition, the views of the dentists taking part, of the profession's representatives, and of the administrators of the systems were obtained. No evidence of systematic neglect could be found among the children treated under capitation, but they had fewer fillings, more untreated diseased teeth and similar disease levels to their counterparts treated under fee-for-service. Dentists in capitation carried out fewer fillings, fewer extractions, took fewer radiographs and saw their patients less frequently than their fee-for-service colleagues. PMID- 2306397 TI - The orthodontic skill mix in Sweden. AB - During 1989 I visited the Institute of Postgraduate Dental Education, Jonkoping, Sweden. The trip was funded by a T.C. White Travel Grant from the Royal College of Physicians & Surgeons of Glasgow and the Cordent Dental Trust. The aim of the visit was to observe the methods of teaching orthodontics to general dental practitioners, in Jonkoping, and to discover the role of dental nurses in providing orthodontic treatment in Sweden. PMID- 2306399 TI - Study now, pay later. PMID- 2306398 TI - The MGDS: a candidate's view--Part 1. AB - After 10 years in general practice, Reading dentist Charles Scola felt the need for a challenge and decided to work for the Membership of General Dental Surgery. In this article, the first of three, he describes the initial planning he undertook. Subsequent articles will cover the preparations involved and sitting the exam itself, which he did at the Royal College of Surgeons of England. While the author makes reference to its particular regulations, the Royal College of Surgeons of Edinburgh and the Royal College of Physicians & Surgeons of Glasgow also offer this exam under different formats. PMID- 2306400 TI - Changing perceptions of the requirements of cavity preparations'. PMID- 2306401 TI - The unpredictability of impacted third molar development--the danger of passive observation. PMID- 2306402 TI - 'Dental sensitivity and bereavement'. PMID- 2306403 TI - British Paedodontic Society's policy document--The Dental Needs of Children. PMID- 2306404 TI - 'Human plaque pH responses to meals and the effects of chewing gum'. PMID- 2306405 TI - 'Wisdom tooth waiting lists'. PMID- 2306406 TI - 'To retract or not to retract'. PMID- 2306407 TI - 'Atrophy of fungiform papillae following lingual nerve damage--a suggested mechanism. PMID- 2306408 TI - 'Oral surgical instruments'. PMID- 2306409 TI - Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy? AB - 1. Normally during walking, the heel strikes the ground before the forefoot. Abnormalities of foot strike in idiopathic Parkinson's disease may be amenable to therapy: objective measurements may reveal response which is not clinically apparent. Occult changes in foot strike leading to instability may parallel the normal, age-related loss of striatal dopamine. 2. The nature of foot strike was studied using pedobarography in 160 healthy volunteers, aged 15 to 91 years. Although 16% of strikes were made simultaneously by heel and forefoot, there were no instances of the forefoot preceding the heel. No significant effect of age on an index of normality of foot strikes was detected (P greater than 0.3). 3. The effect on foot strike of substituting placebo for a morning dose of a levodopa/carbidopa combination was studied in a double-blind, cross-over trial in 14 patients, aged 64 to 88 years, with no overt fluctuations in control of their idiopathic Parkinson's disease in relation to dosing. On placebo treatment there was a highly significant (P = 0.004) reduction in the number of more normal strikes, i.e. heel strikes plus simultaneous heel and forefoot strikes. The effect appeared unrelated to the corresponding difference between active and placebo treatments in plasma concentration of levodopa or a metabolite of long half-time, 3-O-methyldopa (3OMD). However, it correlated negatively (P less than 0.05) with the mean of the 3OMD concentrations. 4. It appears that some abnormalities of foot strike due to Parkinson's disease are reversible. Employing test conditions, designed to provoke abnormalities of foot strike, might be useful in screening for pre-clinical Parkinson's disease. PMID- 2306410 TI - The measurement of haloperidol and reduced haloperidol in hair as an index of dosage history. AB - 1. We report a method for measuring the concentrations of haloperidol (HL) and its major active metabolite, reduced haloperidol (RHL), in human scalp hair. 2. Hair samples were obtained from 59 patients who had been taking HL at fixed daily doses for more than 4 months and whose compliance was good. A morning pre-dose plasma sample was also obtained from 48 of these patients. 3. The concentrations of HL and RHL in hair (ng mg-1 hair) correlated significantly both with the daily dose (micrograms kg-1 body weight) of HL (r = 0.682, P less than 0.001 for HL and r = 0.813, P less than 0.001 for RHL, n = 59) and with the trough concentration (ng ml-1) of the corresponding compound in plasma at steady state (r = 0.558, P less than 0.001 for HL and r = 0.563, P less than 0.001 for RHL, n = 48). The correlation coefficients were slightly higher using the sum of the concentrations of both substances in hair (r = 0.829 for the correlation with daily dose and r = 0.609 for that with trough concentration). 4. Hair from other patients, in whom the dosage of HL had been changed within a few months prior to sampling, was sectioned into 1 cm-long portions successively from the roots and the concentrations of both compounds in each portion were measured. Assuming a growth rate of 1-1.5 cm/month, a history of individual dosage could be deduced in all patients from the distribution of the drug and metabolite along the single hair length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306411 TI - The effect of age on serum concentrations of albumin and alpha 1-acid glycoprotein. AB - 1. Human serum albumin (HSA) concentrations and alpha 1-acid glycoprotein (AAG) concentrations were measured in 68 subjects, 35 males and 33 females, aged 20-90 years without evidence of acute or chronic inflammatory disease or malignancy. Subjects were drug free for at least 1 month. HSA and AAG concentrations were measured using rate nephelometry. 2. Age had no effect on alpha 1-acid glycoprotein concentration, whereas plasma albumin levels decreased as a function of age in both sexes. We observed no differences between males and females in the plasma concentrations of HSA and AAG. 3. These data show that in healthy subjects the HSA concentration decreases with increasing age, whereas age, uncomplicated by disease does not influence AAG concentration. PMID- 2306412 TI - 99mTc-neoglycoalbumin (NGA)-binding to human hepatic binding protein (HBP) in vitro. AB - 1 Neoglycoalbumin (NGA) was synthesised by covalent coupling of 2-imino-2 methoxyethyl-1-thio-beta-D-galactopyranoside (IME-thiogalactose) to the primary amino groups of human serum albumin (HSA). NGA was purified by ultrafiltration and size exclusion h.p.l.c. (SEC). 99mTc-labelling was performed with and without SEC purification. 2 Estimation of 99mTc-NGA-binding to human hepatic binding protein (HBP) revealed a complex behaviour indicating saturable high- and low affinity sites. The high-affinity binding capacity was 1.1 +/- 0.4 pmol mg-1 human liver plasma membrane protein, the low-affinity binding capacity was 6.2 +/ 1.8 pmol mg-1 liver plasma membrane protein. The apparent equilibrium dissociation constants were 2.4 +/- 1.2 and 18.4 +/- 4.8 nM, respectively. 3 Specific binding of 99mTc-NGA to human HBP in the presence of 100 microM unlabelled NGA, Ca++ and Mg++ at pH 7.5 and 37 degrees C reached 85 +/- 5% at equilibrium. The amount of ligand specifically bound increased with the amount of human liver membrane protein added. The concentration of unlabelled agonist necessary to displace 50% of ligand bound amounted to 100 nM. PMID- 2306413 TI - Diuretic effect and diuretic efficiency after intravenous dosage of frusemide. AB - 1. Frusemide was given intravenously at a dose of 5 mg kg-1 to five healthy volunteers and the diuresis was assessed by frequent spontaneous voiding over 5 h. Urinary volume and contents of sodium, chloride, potassium and frusemide were measured. 2. Diuretic response was evaluated using the sigmoid Emax model and non linear regression of diuresis vs frusemide excretion rate. The time courses of diuresis (pharmacological effect) and diuretic efficiency were constructed from the fitted parameters of the sigmoid Emax model. 3. The frusemide excretion rate associated with maximum efficiency was found, as predicted theoretically, to be less than the excretion rate associated with 50% of maximum effect in four of the five subjects in whom the slope factor was less than 2. 4. The effect over time is dependent both on the instantaneous drug effect but also on its pharmacokinetic properties and mode of administration. An intravenous bolus is the least efficient mode of administration while a controlled input producing a frusemide excretion at maximum efficiency should yield up to a 2.3 times higher diuretic response. PMID- 2306414 TI - An assessment of the effects of impaired renal function and haemodialysis on the pharmacokinetics of fluconazole. AB - 1. The oral pharmacokinetics of fluconazole were studied in three groups of volunteers (n = 5) with various degrees of renal function (GFR greater than 70 ml min-1; 20-70 ml min-1; less than 20 ml min-1) and in a group of patients with chronic end-stage renal failure requiring regular haemodialysis. 2. The pharmacokinetics of fluconazole were markedly affected by impaired renal function with the elimination of half-life in Group III (GFR less than 20 ml min-1) being approximately three times that observed in normal volunteers (Group I). 3. Fluconazole renal clearance was positively correlated with GFR. 4. Non-renal clearance of fluconazole decreased with decreasing renal function. 5. Approximately 38% of the 50 mg dose of fluconazole was removed by haemodialysis extending over a 3 h period. PMID- 2306415 TI - Altered sensitivity to amiloride in cystic fibrosis. Observations using cultured sweat glands. AB - 1. Using cultured epithelia from sweat glands, derived from both cystic fibrosis and normal subjects, the relationship between amiloride concentration and the inhibition of electrogenic sodium transport was measured, under short circuit conditions. 2. The Kd for amiloride in cultures from normal subjects was 0.64 microM (n = 6) while in cultures derived from CF patients the value was 1.07 microM (n = 4). The values were significantly different (P less than 0.02, ANOVA). 3. In cultures from normal sweat glands, bathed in solutions free of permeable anions (chloride/bicarbonate), the Kd for amiloride rose to a value greater than found in CF tissues (2.3 microM). In CF epithelia subject to the same conditions the abnormally high value increased further, so that in solutions without permeable anions normal and CF cultures behaved similarly. 4. In cultures derived from normal and CF tissues lowering the sodium concentration to 10 mM also lowered the Kd for amiloride, however the shift was greater for CF cultures. 5. Several possible explanations for the results are discussed. The most probable is that the relatively more positive apical membrane potential in CF epithelia opposes the interaction of amiloride with the sodium channel, implying that complex formation is potential sensitive. PMID- 2306416 TI - A novel method for culturing sweat gland epithelia: comparison of normal and cystic fibrosis tissues. AB - A new method is described to produce epithelial sheets by direct explantation of human sweat glands onto matrigel-coated millipore filters. The method is applicable to whole glands, separated coils or ducts and to normal and CF tissues. Electrogenic transport studies show that epithelia develop sodium transporting capability, even when explants are derived from secretory coils. PMID- 2306417 TI - Evidence for the polymorphic oxidation of debrisoquine in the Thai population. AB - Debrisoquine polymorphism has been studied extensively in Caucasian populations. The prevalence of the poor metaboliser phenotype is 3-10% in European and American Caucasian populations but appears to be very low in Asian populations. This study was carried out to determine the metabolic oxidation status in 173 Thai subjects. Phenotyping was performed using the metabolic ratio (MR) calculated as the 0-8 h urinary output of debrisoquine/0-8 h urinary output of 4 hydroxydebrisoquine after oral administration of 10 mg debrisoquine hemisulphate. Two subjects (1.2%) were phenotyped as poor metabolisers; they had MR values of 13.17 and 92.04. The incidence of the poor metaboliser phenotype of debrisoquine oxidation of 1.2% seems to be lower in the Thai population compared with that in various Caucasian populations. PMID- 2306418 TI - Quinidine kinetics after a single oral dose in relation to the sparteine oxidation polymorphism in man. AB - The kinetics at a single oral dose (400 mg) of quinidine were studied in four extensive metabolizers (EM) and four poor metabolizers (PM) of sparteine. The clearance of quinidine by 3-hydroxylation was significantly lower in PM than in EM, but the difference was small (25-30%). This finding suggests that 3 hydroxylation, in part, is catalyzed by the same isoenzyme of cytochrome P450, P450db1 which oxidizes sparteine. Otherwise, no significant phenotypic differences in total or metabolic clearance were found and it is concluded that the metabolism of quinidine is largely carried out by P450 isoenzymes different from P450db1. A biexponential decline in the log plasma quinidine concentration vs time curves was observed in all subjects, and the mean elimination half-life was 11-12 h. This is about twice as long as generally reported in the literature. PMID- 2306419 TI - Cimetidine as modulator of the cell-mediated immune response in vivo using the tuberculin skin test as parameter. AB - The in vivo pharmacological effects of cimetidine on delayed hypersensitivity reactions in healthy volunteers were studied using the tuberculin skin test as parameter. Cimetidine clearly enhanced this reaction when it was administered well before antigenic stimulation. PMID- 2306420 TI - The effect of propranolol on paracetamol metabolism in man. AB - Ten healthy volunteers were treated for 4 days with 160 mg propranolol HCl and placebo in random order. At the end of each treatment salivary antipyrine kinetics and the plasma kinetics and urinary excretion of paracetamol and its major metabolites were measured following a 1500 mg oral dose. Propranolol prolonged the half-life of antipyrine by 11 +/- 5% (mean +/- s.e. mean) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol increased the half-life of paracetamol by 25 +/- 12% (P less than 0.05) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol decreased the partial clearance of paracetamol to its cysteine and mercapturate derivatives by 16 +/- 3% (P less than 0.05) and 32 +/- 7% (P less than 0.05), respectively. The partial clearance to the glucuronide conjugate was decreased by 27 +/- 6% (P less than 0.05), whereas that to sulphate was not changed significantly. Propranolol inhibits paracetamol metabolism predominantly through inhibition of the oxidation and glucuronidation pathways. PMID- 2306421 TI - Lack of effect of atenolol and nadolol on the metabolism of theophylline. AB - The effects of 7 days of pretreatment with atenolol, 150 mg day-1, or nadolol, 80 mg day-1, on the pharmacokinetics and metabolism of theophylline were determined in six male smokers. Theophylline clearance, volume of distribution, half-life and the urinary excretion of theophylline and its metabolites were unchanged during either treatment compared with control. PMID- 2306422 TI - Increased volume of distribution prolongs midazolam half-life. AB - It has recently been shown by several investigators that the half-life (t1/2) of midazolam is prolonged (greater than 7 h) in a small proportion of the population. One group has inferred that this subpopulation represents a group of slow metabolizers of midazolam to alpha-OH-midazolam. Others disagree and postulate that there is an increase in the volume of distribution (V) resulting in a prolonged t1/2. This controversy led us to report experience from 90 subjects and patients where t1/2, V, and clearance (CL) were determined by both model-dependent and -independent pharmacokinetic analysis. We found a 5.6% (5 of 90) incidence of prolonged t1/2, similar to that previously reported. V was clearly increased without a decrease in CL in the five subjects with prolonged t1/2. Thus, the prolonged t1/2 is secondary to an increase in V and not a result of alterations in CL and metabolism. PMID- 2306423 TI - Safety of vancomycin in acute porphyria. AB - A 27-year-old female with acute intermittent porphyria presented in a life threatening acute attack. She developed a Staphylococcus aureus septicaemia and was treated with intravenous vancomycin for 4 weeks. Porphyrins and their precursors were monitored and declined during the course of therapy. The safety of vancomycin in people with the acute porphyrias has not previously been documented, and we conclude that, in this case, the use of vancomycin was without ill-effect. PMID- 2306424 TI - Excretion of sotalol in breast milk. PMID- 2306425 TI - The value of therapeutic drug monitoring. PMID- 2306426 TI - Child outcome following mid-trimester amniocentesis: development, behaviour, and physical status at age 4 years. AB - Four-year-old children whose mothers had mid-trimester amniocentesis (n = 88) were compared with children whose mothers chose not to have the procedure (n = 46). Intelligence, visual-motor-perceptual skills, language, behaviour, social competence, temperament, physical growth, hearing, and middle-ear function were measured using standardized procedures. Health histories were obtained by maternal report. The results suggest that the wide range of developmental and behavioural variables studied is not influenced by removal of amniotic fluid in the mid-trimester. However, mothers who had amniocentesis were more likely to report a history of ear infections in their child (P = 0.04). In support of this finding were the results of audiological assessment which demonstrated a trend toward a higher rate of bilateral middle-ear impedance abnormalities in children whose mothers had amniocentesis (P = 0.06). Further study of the upper respiratory system is recommended to explore potential long-term sequelae of mid trimester amniocentesis. PMID- 2306427 TI - Using Lamicel to expose high cervical lesions during colposcopic examinations. AB - Women with abnormal cervical cytology and an unsatisfactory colposcopic examination were offered Lamicel in an attempt to expose the entire transformation zone. The sponge, which softens, dilates and effaces the cervix, was passed intracervically in 41 patients in whom the entire squamocolumnar junction could not be seen. After 3-4 h the sponge was removed and colposcopy repeated. In 29 of the 41 patients the lesion and the squamocolumnar junction were now fully visible. Twenty-five of these patients were spared a cone biopsy. PMID- 2306428 TI - How frequently need vaginal smears be taken after hysterectomy for cervical intraepithelial neoplasia? AB - A retrospective longitudinal review identified 341 women who had had a hysterectomy in association with CIN 3, in Tayside Region, during the years 1967 1977; 219 (64%) had completed 10 years of cytology follow-up and of 140 women eligible for 15-year smears 79 (56%) completed the 15-year follow-up. Eight (4%) of the 219 patients developed abnormal cytology, but in six, smears reverted to normal spontaneously. Two patients had persistently abnormal smears and vaginal intraepithelial neoplasia (VAIN) was diagnosed. Only one patient completing 15 year follow-up had an abnormal smear and VAIN later diagnosed. No patient over this 15-year period developed invasive vaginal carcinoma. Sixty vaginal carcinomas were identified during the period 1957-1987 from the gynaecology cancer register; only one was associated with a previous diagnosis of CIN 3 at hysterectomy. With such data we would propose screening 6-monthly during the first post-operative year and then at 2 years. If these smears were normal, the patient could then revert to the normal screening programme. PMID- 2306429 TI - The effect of maternal work on fetal growth and duration of pregnancy: a prospective study. AB - The effect on birth outcome of work requiring different degrees of physical exertion was examined among 15,786 pregnant women who were followed through the Guatemalan Social Security Institute's hospital. Work inside and outside the home was ascertained through a questionnaire administered to each women before delivery. Odds ratios were adjusted for household income, maternal height and age, and birthweight of previous infant. Women with three or more children and no household help were at increased risk for small-for-gestational-age (SGA) births compared with women with family (odds ratio (OR) 1.79; 95% confidence interval (CI) 1.31, 2.47) or hired help (OR 2.0; 95% CI 1.16 to 3.33). Compared with office work, manual work increased the risk for an SGA (OR 1.32; 95% CI 1.12 to 1.56) and SGA/preterm birth (OR 2.56; 95% CI 1.10 to 5.96). Work in a standing compared with sitting position significantly increased the risk for a preterm birth (OR 1.56; 95% CI 1.04 to 2.60). There was a significant positive trend in frequency of SGA and SGA/preterm birth with an increase in the physical demands at work, as measured by an activity score. These data suggest that interventions to reduce physical exertion among pregnant women could improve birth outcome. PMID- 2306430 TI - Maternal thyroid hormones and outcome of pre-eclamptic pregnancies. AB - Plasma concentrations of total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3), thyroid-stimulating hormone (TSH), plasma albumin and urate were measured in 39 proteinuric pre-eclamptic patients presenting before labour. Pre-eclamptic patients had significantly lower FT4 and higher TSH concentrations compared with values in third trimester normotensive pregnancies. There was a significantly higher frequency of lower TT4, TT3 and high TSH levels in the subgroup of pre-eclamptic patients who had low-birthweight babies. Thyroid hormone concentrations were not correlated with gestation at delivery or birthweight but, with the exception of FT4, were correlated with plasma albumin and urate concentrations. Plasma TSH correlated with birthweight and with plasma urate. The results suggest that mild biochemical hypothyroidism may be found in proteinuric pre-eclampsia, and the concentrations of TT4, TT3, FT3 and TSH may reflect the severity of pre-eclampsia. PMID- 2306431 TI - Effects of bilateral oophorectomy on lipoprotein metabolism. AB - The effects of surgical menopause on lipoprotein levels and their time course were studied in 31 premenopausal women who were undergoing hysterectomy and bilateral oophorectomy for non-malignant conditions. Lipoprotein levels were measured before oophorectomy and afterwards at 6 and 12 weeks, then at intervals of 3 months for 18 months. Low density lipoprotein (LDL) cholesterol levels rose significantly (P less than 0.05) in the 6 weeks after operation from a mean of 3.57 (SD 0.66) mmol/l to 4.21 (SD 0.84) mmol/l with no significant changes thereafter. There were no significant changes in cholesterol in the other density fractions or in triglyceride levels. High density lipoprotein (HDL) subfractions were measured in 10 of the women to assess any change in the relative amounts of cholesterol carried on HDL2 and HDL3, since the protective effect of HDL is believed to be conferred by the HDL2 fraction only. No significant change was found in either fraction. The increase in LDL cholesterol would be expected to result in an appreciable increase in the risk of developing coronary heart disease, but cannot wholly account for the increase in cardiovascular disease associated with oophorectomy. PMID- 2306432 TI - Postpartum haemolytic uraemic syndrome precipitated by antibiotics. Case report. PMID- 2306433 TI - Maternal mortality in developing countries. PMID- 2306434 TI - Needle aspiration of simple ovarian cysts in pregnancy. Case reports. PMID- 2306435 TI - Virilizing nodular ovarian stromal hyperthecosis, diabetes mellitus and insulin resistance in a postmenopausal woman. PMID- 2306436 TI - Measurement of cardiac output in pregnancy by thermodilution and impedence techniques. PMID- 2306437 TI - Glaucoma: is there light at the end of the tunnel? PMID- 2306438 TI - Reliability of photographs for grading trachoma in field studies. AB - The validity and reliability of the use of photographs to assess active trachoma and scarring was studied in a village where the disease was hyperendemic. One hundred and thirty six subjects were graded clinically and had photographs taken of the upper tarsal plate. Agreement between the clinical grade in the field and the grade on the photograph was very good for follicular trachoma, severe trachoma, and scarring (kappa statistic values were 0.71, 0.74, and 0.73 respectively). In field studies photographic documentation of trachoma appears to be a valid and reliable approach. PMID- 2306439 TI - Topical use of indomethacin on the day of cataract surgery. AB - The use of topical indomethacin in the prevention of surgically induced miosis has been documented. However, in these previous prospective trials this prostaglandin synthetase inhibitor was administered the day before surgery. With the frequency of 'day case' cataract surgery increasing, an efficient preoperative mydriatic regimen is important. In this study we considered the use of topical indomethacin as an addition to a regimen already implemented. One hundred and fourteen eyes underwent intercapsular cataract surgery, of which 64 were randomised to receive topical aqueous indomethacin one hour beforehand, and 50 eyes, which did not receive indomethacin formed the comparison group. Topical indomethacin reduced the miosis which occurs during cataract surgery whether performed under local or general anaesthesia. The operating time was shorter for eyes with less surgically induced miosis. PMID- 2306440 TI - Pseudophakic accommodation? A study of the stability of capsular bag supported, one piece, rigid tripod, or soft flexible implants. AB - A group of pseudophakic patients was investigated to determine whether their implants shift along an anteroposterior axis under different conditions of ciliary muscle stimulation. There was no statistically significant change in refraction after either pilocarpine or cyclopentolate administration. A change in anterior chamber depth between the position after pilocarpine and that after cyclopentolate was found. It appears that rigid posterior chamber implants do move backwards on ciliary muscle relaxation, but by a maximum 0.25 mm. This is not thought to represent a mechanical threat to ocular health. It is also not enough to account for the apparent accommodative ability of some pseudophakic patients. The possible causes for this phenomenon are discussed. PMID- 2306441 TI - Association between intraocular pressure and loss of visual field in chronic simple glaucoma. AB - This paper reports the analyses on data from 747 patients with chronic simple glaucoma (CSG) recorded in the King's College Hospital glaucoma data base between January 1970 and February 1985, having a mean follow-up time of 5.1 years (mode 8 years) with the object of determining the relationship of intraocular pressure (IOP) and visual field loss in CSG. A highly significant negative relationship was found between the presenting visual field coefficient (FC) and the untreated IOP (r = -0.26, p = 0.0001) - that is, the higher the IOP on detection, the worse is the visual field. A weak negative correlation was present between the change of FC per year and the treated IOP (r = -0.06), p = less than 0.05). At treated IOPs less than or equal to 18 mmHg visual field loss averaged 0.6 unit per year and for IOPs greater than 18 mmHg the average loss was 1.2 units per year. The data confirm both the importance of a raised IOP in the causation of chronic glaucomatous visual field loss and the importance of reducing the IOP in patients with chronic simple glaucoma. PMID- 2306442 TI - Central retinal vein occlusion in people aged 40 years or less: a review of 17 patients. AB - Seventeen patients with central retinal vein occlusion aged 40 or under were reviewed. Ocular involvement was characteristically unilateral, with moderate degrees of retinal haemorrhage, little retinal ischaemia, and a tendency to optic disc swelling. Visual prognosis was good. Follow-up showed that most patients have good general health and no involvement of the fellow eye. There was little evidence to support an inflammatory aetiology or underlying vascular disease in most of the patients. An alternative explanation for the development of CRVO in young patients might be a congenital anomaly of the central retinal vein. PMID- 2306443 TI - Topical fluconazole for experimental candida keratitis in rabbits. AB - Using a reproducible model of Candida albicans keratitis in rabbits we studied the effect of topical fluconazole, a new triazole. Candida albicans DSM 70010 (2.5 X 10(5) cells) was injected into the corneal stroma of both eyes of 21 rabbits. All eyes developed a corneal ulcer. Forty-eight hours after inoculation the animals were divided into three groups: (1) 14 eyes, received fluconazole (2 mg/ml) and the epithelium subsequently removed; (2) 14 eyes, received only fluconazole drops; (3) 14 eyes, received 0.9% NaCl: half of this group was also debrided. We applied one drop of either substance 10 times a day for 24 days. A further six rabbits were used to judge if the drug penetrated into the cornea and aqueous humour. There was a highly significant difference between the fluconazole groups (1,2) and the control group (3) as to hypopyon and complications (descemetocele, corneal perforation) as well as recultivation of C. albicans from corneal tissue. The difference between the fluconazole groups with and without debridement was not significant. The drug penetrated into the cornea and aqueous humour of both uninflamed and inflamed eyes. PMID- 2306444 TI - Magnetic resonance imaging of juxtapapillary plaques in cadaver eyes. AB - Adequate treatment of juxtapapillary melanomas with episcleral plaque brachytherapy using lower energy radiation sources may be difficult because of uncertainties regarding the relationship of the plaque to the optic nerve and tumour base. We obtained magnetic resonance images of a dummy plaque placed in a juxtapapillary location in cadaver specimens. Although it is possible to place a plaque in close association with the optic nerve sheath, a tissue barrier exists which may prevent actual contact between the plaque and nerve. Posterior tilting of the plaque may also occur. Because of these uncertainties regarding plaque placement, juxtapapillary melanomas should be considered a distinct subgroup when evaluating the efficacy of radioactive plaque brachytherapy in the treatment of choroidal melanoma. PMID- 2306445 TI - Retinal dysfunction as an initial ophthalmic sign in AIDS. AB - Three cases of patients with AIDS in whom severe retinal dysfunction preceded the development of widespread funduscopic abnormalities are presented. The disparity between the minimal extent of visible retinal lesions and the severe loss of retinal function was confirmed by visual field and electroretinographic studies. This pattern of early visual loss in AIDS patients may represent infection of the retina by the HIV virus. PMID- 2306446 TI - Adult gonococcal keratoconjunctivitis with AIDS. AB - Gonococcal eye infection in adults is an uncommon cause of blindness, where prompt diagnosis and effective treatment are essential in the prevention of ophthalmic morbidity. We present a case report detailing the management and complications encountered in this condition in a patient coinfected with human immunodeficiency virus (HIV). PMID- 2306447 TI - Morning glory syndrome: a histopathological study. AB - The clinical and histopathological findings in a case of morning glory syndrome are described. Axial optic nerve retrodisplacement into a peripapillary scleral ectasia (staphyloma), absence of fibrous lamina cribrosa, and optic nerve atrophy were associated with various other, non-inherent ocular developmental anomalies. The uninterrupted lining of the inner wall of the staphyloma by one-layered, normal retinal pigment epithelium proves that the syndrome is not due to a neuroectodermal closure defect. PMID- 2306449 TI - Amitosis in human donor corneal endothelium--a serendipity? PMID- 2306448 TI - Microphthalmos with colobomatous orbital cyst: clinical, histological, immunohistological, and electronmicroscopic findings. AB - A case of unilateral microphthalmos with orbital cyst is presented. This rare and severe malformation is a non-hereditary disorder. Pathologically it represents a failure in the closure of the embryonic fissure at the 7-14 mm stage of gestation. Staining for neurofilaments permitted the identification of rudimentary optic nerve fibers within the gliomatous cyst wall. Special stains for glial fibrillary acidic protein as well as scanning and transmission electron microscopy were used to characterise the neuroglial cell lining of the cyst wall, and to show microvilli on its inner surface. PMID- 2306450 TI - Measurement of corneal diameter. PMID- 2306451 TI - Plasmodium knowlesi induces alterations in phosphatidylcholine and phosphatidylethanolamine molecular species composition of parasitized monkey erythrocytes. AB - Using high performance liquid chromatography and gas-liquid chromatography, we have characterized the phosphatidylcholine and phosphatidylethanolamine molecular species composition of trophozoite and schizont forms of Plasmodium knowlesi parasitized erythrocytes. Similarly, we determined these parameters in the erythrocyte membranes of trophozoite parasitized cells, unparasitized erythrocytes from infected monkeys before and after a chloroquine treatment and erythrocytes from monkeys that had never been infected. Plasma phosphatidylcholine molecular species composition was also studied. P. knowlesi parasitized erythrocytes presented higher amounts of 16:0/18:2 phosphatidylcholine than the various control cells, which appeared to be compensated for by a decrease in 18:0/20:4-, 16:0/20:3-, 16:0/18:1-, 18:0/18:2-, 18:0/20:3-, 16:0/16:0- and 16:0/18:0-phosphatidylcholines. In the case of phosphatidylethanolamine, the alterations were quantitatively of greater importance and consisted of an increase in, again, 16:0/18:2 phosphatidylethanolamine and a decrease in several species containing 20:4, namely 16:0/20:4-, 18:0/20:4- and 18:1/20:4-phosphatidylethanolamine; also the levels of alkoxy-phosphatidylethanolamines were markedly decreased. P. knowlesi development within monkey erythrocytes therefore appears to be associated with changes in phosphatidylcholine and phosphatidylethanolamine molecular species in the whole parasitized cell. These alterations are also exhibited by the host cell membrane, which provides the first experimental evidence that the parasite is able to manipulate the erythrocyte membrane lipid species composition. The consequences of these alterations on membrane physiology are discussed, as well as the implications that these data may have on the trafficking of phosphatidylcholine and phosphatidylethanolamine in the erythrocytes of P. knowlesi infected monkeys. PMID- 2306452 TI - Mixed monolayers of natural and polymeric phospholipids: structural characterization by physical and enzymatic methods. AB - This study has focused on physical characterization and enzymatic hydrolysis of mixed monolayers of a natural phospholipid substrate and a polymerizable phospholipid analogue. Such a mixed system presents the possibility to stabilize model biomembranes, vary the molecular environment within the layer through polymerization and simultaneously examine these influences on monolayer structure. Phospholipase A2 was used here as a sensitive probe of the molecular environment within these mixed, polymerizable monolayers to complement information obtained from isotherm and isobar data. The results clearly show a strong influence of molecular environment on phospholipase A2 activity, even if differences in the physical state of mixed monolayers are not detectable with isotherm and isobar measurements. Physical characterization indicated that both monomeric and polymeric mixed monolayers were phase-mixed. Enzyme hydrolysis, however, showed large differences in the ability of the enzyme to selectively hydrolyze the natural phosphatidylcholine component from the monomeric as opposed to the polymeric mixtures. This demonstrates a high sensitivity of phospholipase A2 to distinguish subtle differences in molecular arrangement within mixed monolayers on a molecular level. PMID- 2306453 TI - Interaction of Triton X-100 and octyl glucoside with liposomal membranes at sublytic and lytic concentrations. Spectroscopic studies. AB - The molecular mechanism of the solubilisation of phospholipid bilayers by nonionic detergents was studied by turbidity changes, carboxyfluorescein fluorescence dequenching, steady-state and time-resolved fluorescence anisotropy of DPH, lifetime measurements, ANS binding and 31P-NMR. Particular attention has been paid to the effective detergent-to-lipid ratio in the lipid phase. The disturbance of the bilayer arrangement varies considerably for various detergents depending on the hydrophilic and lipophilic parts of the molecule. Small amounts of detergents with low CMC (e.g. Triton X-100) can even induce an optimisation of packing of the lipid molecules. PMID- 2306454 TI - The effect of lipid composition on the relaxivity of Gd-DTPA entrapped in lipid vesicles of defined size. AB - The effects of lipid composition on the relaxivity of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) entrapped in lipid vesicles has been examined for vesicles of different sizes composed of egg phosphatidylcholine and cholesterol in various molar ratios, as well as the stability of those same vesicles in human serum at 37 degrees C. It is found that the incorporation of cholesterol decreases the apparent relaxivity of the entrapped Gd-DTPA, concomitant with an increase in vesicle stability in serum. Cholesterol has little effect on relaxivity when incorporated at ratios up to 20 mole percent, but has an increasing effect at higher mole percentages. These results correlate with the known effects of cholesterol on the osmotic water permeability coefficients of various model membrane systems and suggest that it is the water flux across the vesicle bilayer that is limiting to the T1 relaxivity of the entrapped Gd-DTPA. The incorporation of up to 20 mole percent cholesterol has little effect on the stability of the vesicles in serum, whereas vesicles containing more than 20 mole percent cholesterol show greater increases in stability. It was also found that the stability of vesicles depends upon the size of the vesicles; smaller vesicles are less stable in human serum at 37 degrees C than larger vesicles. PMID- 2306455 TI - Influence of vitamin E on phosphatidylethanolamine lipid polymorphism. AB - The effect of vitamin E, in its major form alpha-tocopherol and its synthetic analog alpha-tocopheryl acetate, on phosphatidylethanolamine lipid polymorphism has been studied by mean of differential scanning calorimetry and 31P-nuclear magnetic resonance techniques. From the interaction of these tocopherols with dielaidoylphosphatidylethanolamine it is concluded that both molecules promote the formation of the hexagonal HII phase at temperatures lower than those of the pure phospholipid. When the tocopherols were incorporated in the saturated dimiristoylphosphatidylethanolamine, which has been shown not to undergo bilayer to hexagonal HII phase transition, up to 90 degrees C, they induce the phospholipid to partially organize in hexagonal HII phase. From our experiments it is shown that alpha-tocopherol is more effective than its analog in promoting HII phase in these systems. It is also shown that, while alpha-tocopheryl acetate does not significantly perturb the gel to liquid-crystalline phase transition of dimirystoylphosphatidylethanolamine, alpha-tocopherol does so and more than one peak appears in the calorimetric profile, indicating that lateral phase separations are taking place. PMID- 2306456 TI - Design and synthesis of basic peptides having amphipathic beta-structure and their interaction with phospholipid membranes. AB - Basic amphipathic beta-structural peptides, Ac-(Ser-Val-Lys-Val)n-NHCH3 (1n, n = 1-3) and Ac-(Lys-Val)n-NHCH3 (2n, n = 2-4), were synthesized and their interaction with DPPC and DPPC-DPPG (3:1) bilayers was studied by CD, dye-leakage and fluorescence experiments. The CD data indicated that oligopeptides consisting of more than eight residues with alternating hydrophobic (Val) and hydrophilic amino acids (Ser and Lys) were able to form an amphipathic beta-structure in acidic phospholipid bilayers, but not or weakly in aqueous solution and in neutral phospholipid bilayers. The dye-leakage experiment showed that the basic amphipathic beta-structural peptides interact with acidic phospholipid bilayers to perturb them, but less effectively compared with basic amphipathic alpha helical peptides. Fluorescent spectroscopic data suggest that hydrophobic side of the amphipathic peptides may immerse into membrane without deep penetration. Based on these results, we postulate that the formation of the basic amphipathic beta-structure on acidic lipid bilayers may be due to the combined effect of electrostatic and hydrophobic interactions between basic peptides and acidic lipid bilayers. PMID- 2306457 TI - Infrared spectra of phospholipid membranes: interfacial dehydration by volatile anesthetics and phase transition. AB - Fourier-transform infrared attenuated total reflection (ATR) spectroscopy was used to study the effect of volatile anesthetics on fully hydrated dipalmitoylphosphatidylcholine (DPPC) vesicle membranes. The main phase transition was monitored by the change in the C-H2 asymmetric stretching frequencies of the lipid tails. The surface property was analyzed by the changes in the P = O stretching, (CH3)3-N+ stretching of the hydrophilic head, and C = O stretching of the glycerol skeleton. The partial pressures of those agents that decreased the transition temperature 1.0 C degree were halothane 0.75, enflurane 1.90 and CCl4 0.85 kPa. At a 2:1 lipid/anesthetic mole ratio, the polar anesthetics, halothane and enflurane, increased the ratio of (P = O stretching band area)/((CH3)3-N+ stretching band area) by 26.3% and 21.1%, respectively, whereas apolar CCl4 increased it 10.5%. The water molecules bound to the P = O moiety are apparently replaced by the anesthetic molecules. The deconvoluted C = O spectra showed two peaks: free sn-1 that is closer to the lipid core and hydrogen-bonded sn-2 that is closer to the polar head. Addition of halothane and enflurane, but not CCl4, increased the number of peaks to three. The third peak is free sn-2, formed by disrupting hydrogen-bonding to water. Because the temperature-induced spectral change was limited to C-H2 stretching at the main phase transition, the effects of anesthetics on the lipid membrane structure are not identical to temperature elevation. Among anesthetics, the effects of apolar and polar molecules on the interfacial properties are different. PMID- 2306458 TI - The quantitative determination of metabolites of 6-mercaptopurine in biological materials. VII. Chemical synthesis by phosphorylation of 6-thioguanosine 5' monophosphate, 5'-diphosphate and 5'-triphosphate, and their purification and identification by reversed-phase/ion-pair high-performance liquid chromatography and by various enzymatic assays. AB - A fast and reliable two-step method has been established for the chemical synthesis of 6-thioguanosine 5'-monophosphate, 6-thioguanosine 5'-diphosphate and 6-thioguanosine 5'-triphosphate starting from the ribonucleoside. In the first step, 6-thioguanosine dissolved in triethyl phosphate, at high yield reacts with phosphorus oxide trichloride to 6-thioguanosine 5'-monophosphate which is purified by anion-exchange chromatography on DEAE-Sephadex using a step gradient of hydrochloric acid. In the second step, 6-thioguanosine 5'-monophosphate dissolved in water, reacts with phosphoric acid in the presence of pyridine/dicyclohexyl carbodiimide and is converted to 6-thioguanosine 5' diphosphate and 6-thioguanosine 5'-triphosphate which are separated from each other and from the 6-thioguanosine 5'-monophosphate by anion-exchange chromatography on DEAE-Sephadex using a gradient of ammonium bicarbonate. Material from each step of the preparation procedure is separated by reversed phase HPLC chromatography and analyzed for its free ribonucleoside content, 5' monophosphate, 5'-diphosphate, 5'-triphosphate and small amounts of unidentified phosphorylated compounds. The purity of the final preparations and the identity of each 6-thioguanosine 5'-phosphate are proven by highly specific enzymatic peak shifting/HPLC analyses using alkaline phosphatase, 5'-nucleotidase, pyruvate kinase, nucleoside diphosphate kinase and combined hexokinase/glucose 6-phosphate dehydrogenase. PMID- 2306459 TI - High-affinity binding sites for oxygenated sterols in rat liver microsomes: possible identity with antiestrogen binding sites. AB - Oxygenated derivatives of cholesterol are known to exhibit a number of biological activities including the inhibition of cholesterol biosynthesis and of cell proliferation, but their mechanism of action remains unclear. Previous studies have identified a cytosolic protein which binds 25-hydroxycholesterol, as well as several other oxysterols, with high affinity, possibly mediating some of their effects. We now report the existence of a high-affinity oxysterol binding site in rat liver microsomes which is distinct from the cytosolic binding protein. Among the oxygenated sterols examined, 5 alpha-cholestan-3 beta-ol-7-one (7 ketocholestanol) had the highest affinity for this microsomal binding site (Kd = 2.7 nM). Using 7-keto[3H]cholestanol as the radioactive ligand, we found that binding of this oxysterol to the microsomal binding site was saturable and reversible and was displaceable by the following oxysterols in descending order of potency: 7-ketocholestanol greater than 6-ketocholestanol greater than 7 beta hydroxycholesterol = 7-ketocholesterol greater than cholesten-3 beta,5 alpha, 6 beta-triol = 7 alpha-hydroxycholesterol greater than 4-cholesten-3-one. All other sterols studied, including, notably, 25-hydroxycholesterol, had little or no inhibitory effect on 7-keto[3H]cholestanol binding. Additional studies revealed that the microsomal oxysterol binding site was probably identical to the antiestrogen binding site described by other workers. First, saturation analysis and kinetic studies demonstrated that the antiestrogen tamoxifen competed directly with 7-keto[3H]cholestanol for the same binding site. Second, the ability of different oxysterols and antiestrogens to inhibit 7 keto[3H]cholestanol binding to the microsomal binding site paralleled their ability to inhibit [3H]tamoxifen binding to the antiestrogen binding site. Third, the tissue distribution of binding sites for 7-keto[3H]cholestanol was similar to that of the antiestrogen binding site. We conclude that: (1) in rat liver microsomes there are high-affinity oxysterol binding sites whose ligand specificity is different from that of the cytosolic oxysterol binding protein; and (2) the microsomal oxysterol binding site is probably identical to the antiestrogen binding site. The biological significance of these observations remains to be explored. PMID- 2306460 TI - An improved method for determination of N-acetyl-L-glutamate by its function as an activator of carbamoyl phosphate synthetase I. AB - N-Acetyl-L-glutamate has been examined with regard to its ability to activate carbamoyl phosphate synthetase I (EC 6.3.4.16). Substance(s) inhibitory to carbamoyl phosphate synthetase, present even in the partially purified preparation of rat liver extracts, interfered with the measurement of acetylglutamate. In the experiments using chelating agents, metals were apparently involved in this inhibition. When the partially purified preparation of liver extract was placed on a Chelex 100 column, the inhibitor was eliminated and accurate measurements of acetylglutamate content could be made. Evidence supporting the validity of this improved method is given. A significant difference was observed between acetylglutamate levels determined by the present method and by the one using aminoacylase I (N-acylamino acid amidohydrolase, EC 3.5.1.14) to hydrolyze acetylglutamate followed by assay of the glutamate generated. We searched for the presence of glutamate derivatives other than acetylglutamate. When impure tissue preparations containing acetylglutamate were treated with a commercial preparation of aminoacylase, there was an excess amount of glutamate apparently derived from compounds other than acetylglutamate. This can lead to an overestimation of the tissue levels of acetylglutamate. PMID- 2306461 TI - Purification and characterization of D-3-aminoisobutyrate-pyruvate aminotransferase from rat liver. AB - D-3-Aminoisobutyrate-pyruvate aminotransferase (EC 2.6.1.40) was purified 1900 fold from rat liver extract. The purified enzyme showed a molecular mass of 180 kDa by gel-permeation HPLC analysis using a TSK gel G3000SW column. Reductive polyacrylamide gel electrophoresis in sodium dodecyl sulfate resulted in identification of a single band of approx. 50 kDa, indicating that the native enzyme is probably a tetrametric protein. The specific activity of the purified enzyme was 1.14 mumol/min per mg protein. D-3-Aminoisobutyrate and beta-alanine were good amino donors. The Km value for L-3-aminoisobutyrate was 100-times larger than that for the D-isomer. The apparent Km values for D-3 aminoisobutyrate and beta-alanine were 35 and 282 microM, respectively. Pyruvate, glyoxylate, oxalacetate, 2-oxo-n-valerate, and 2-oxo-n-butyrate were good amino acceptors. The apparent Km values for pyruvate and glyoxylate were 32 and 44 microM, respectively. PMID- 2306462 TI - The hypolipidemic peroxisome-proliferating drug, bis(carboxymethylthio)-1.10 decane, a dicarboxylic metabolite of tiadenol, is activated to an acylcoenzyme A thioester. AB - Bis(carboxymethylthio)-1.10 decane (BCMTD), a thiodicarboxylic acid, was shown to be a hypolipidemic peroxisome-proliferating drug as it: (a) decreased the total serum triacylglycerols and cholesterol; (b) induced hepatomegaly; (c) increased the peroxisomal beta-oxidation and catalase activity and the activities of the multiorganelle localized enzymes: palmitoyl-CoA synthetase, palmitoyl-CoA hydrolase, glycerophosphate acyltransferase; (d) decreased the carnitine palmitoyltransferase and urate oxidase activities; and (e) induced the bifunctional eonyl-CoA hydratase in peroxisomes. The present study has confirmed the effect of tiadenol administration on the activities of key enzymes involved in hepatic fatty acid metabolism in male rats. However, the hepatic pleiotropic response was more marked with the dicarboxylic acid than with its alcohol. In a separate dose-response study BCMTD was found to be a more potent inducer of peroxisomal beta-oxidation compared to tiadenol. BCMTD can be activated in vitro to its coenzyme A thioester by a dicarboxyl-CoA synthetase. In control and BCMTD treated animals, the synthetase activity was found in all cellular fractions except the cytosolic. Whether the acyl-CoA thioesters of peroxisome-proliferating drugs may be mediators of peroxisomal proliferation should be considered. PMID- 2306463 TI - Variation of the surface properties of Bacillus licheniformis according to age, temperature and aeration. AB - The surface properties of Bacillus licheniformis DSM 603 have been examined as a function of age during cultures in baffled and non-baffled Erlenmeyer flasks, at 30 and 37 degrees C. The elemental composition of the surface was determined by X ray photoelectron spectroscopy and its variation was compared with the electrophoretic mobility and water contact angle. The variations of the surface phosphate concentration during the cultures and according to growth conditions indicate that the determining factor is the total cell concentration. The P/C atomic concentration ratio remains in a range where its variation does not influence the electrophoretic mobility. The decrease and increase of hydrophobicity during cultures at 30 degrees C in baffled and normal flasks, respectively, are paralleled by a variation in the O/C ratio. PMID- 2306464 TI - Cytosolic water-soluble phosphodiester in vertebrate lens. AB - The water-soluble phosphate profiles determined by 31P nuclear magnetic resonance (NMR) of a broad range of vertebrate lenses are presented. We identify threonine ethanolamine phosphodiester (TEP) in intact lenses and lens extracts by its chemical shift and its physical and chemical characteristics. Amongst the species studied, we give the first characterization of frog lens where not only serine ethanolamine phosphodiesters (SEP) but TEP are found. PMID- 2306465 TI - Carbon flux through tricarboxylic acid cycle in rat renal tubules. AB - Our aim was to delineate the effect(s) of chronic metabolic acidosis on renal TCA cycle metabolism. Renal tubules isolated from control and chronically acidotic rats were incubated at pH 7.4 with either 2 mM [2,3-13C]pyruvate or [2 13C]acetate. GC-MS and/or 13C-NMR were utilized to monitor the flux of 13C through pyruvate dehydrogenase, pyruvate carboxylase and the TCA-cycle. With either, precursor acidosis was associated with significantly decreased formation of 13C-labelled citrate, malate, aspartate and alanine and increased formation of glucose, lactate and acetyl-CoA as compared with the control. The results indicate that adaptation of renal metabolism to chronic metabolic acidosis is associated with diminished flux through citrate synthetase and concomitantly increased flux through pyruvate carboxylase. The data suggest that depletion of TCA-cycle intermediates and enhanced ammoniagenesis in the kidney of chronically acidotic rats may be regulated at the site of mitochondrial citrate-condensing enzyme. PMID- 2306466 TI - A monoclonal antibody to free N-acetylneuraminic acid. AB - A monoclonal antibody (70-A) to free N-acetylneuraminic acid was obtained by immunizing mice with its synthetic beta-glycoside, sodium O-[(5-acetamido-3,5 dideoxy-D-glycero-beta-D-galacto-2- nonulopyranosyl)onate]-(2----3)-1,2-di-O tetradecyl-sn-glyce rol, followed by fusing the isolated spleen cells with mouse myeloma cells and cloning positive fusions. 70-A reacted with various synthetic beta-glycosides of N-acetylneuraminic acid and also with cytidine-5' monophosphate-N- acetylneuraminic acid, known as its sole naturally occurring beta-glycoside. The inhibition assay showed that N-glycolylneuraminic acid had slightly lower reactivity than N-acetylneuraminic acid, but other monosaccharides tested, such as N-acetylglucosamine, N-acetylgalactosamine or N acetylmannosamine, had no reactivity toward 70-A. Reactivity of 70-A with free N acetylneuraminic acid was confirmed by measuring the specific binding of N [14C]acetylneuraminic acid to the antibody. The association constant of 70-A with N-acetylneuraminic acid was determined to be 5.96.10(4) M-1 by equilibrium dialysis. PMID- 2306467 TI - A blood group A specific lectin from the seeds of Crotalaria striata. AB - A lectin, monospecific for human blood group A red blood cells was extracted from seeds of Crotalaria striata and purified by molecular sieving on Sephadex G-100 and ion-exchange on DEAE-cellulose. A molecular mass of 30 kDa was determined by SDS-polyacrylamide gel electrophoresis under non-reducing and reducing conditions. Molecular sieving on a Superose 12 column indicated a molecular mass of 110 kDa, suggesting the tetrameric nature of the native protein. Amino-acid composition showed the presence of aminated carbohydrate residues on the lectin. N-terminal amino-acid sequencing showed a striking similarity with the N-terminal sequence of the lectin from Crotalaria juncea, which is blood-group non-specific. The potency order of agglutination inhibition with galactose containing monosaccharides was N-acetyl-D-galactosamine greater than D-galactose greater than D-galactosamine as found for blood-group-A-specific lectins from other species. PMID- 2306468 TI - Loss of cardiac contractility and severe morphologic changes by acutely lowering the pH of the perfusion medium: protection by fatty acids. AB - When the pH of the perfusion medium of rat Langendorff heart, paced at a rate of 300 beats/min, is abruptly lowered from pH 7.5 to 7.0, the hearts stop beating within 6 min in more than half of the cases. Reperfusion with pH 7.5 medium after 10 min pH 7.0 perfusion does not cause contractility to resume within 5 min. The causative factor is intracellular acidosis, resulting in severe morphological alterations of plasma membrane and mitochondria. It is probably initiated by the loss of membrane-bound calcium. Oleate, complexed with albumin included in the perfusion media, protects the hearts. This may be explained by maintenance of capillary flow and limitation of cellular acidosis. PMID- 2306469 TI - Thermodynamic profiles of penicillin G hydrolysis catalyzed by wild-type and Met- --Ala168 mutant penicillin acylases from Kluyvera citrophila. AB - The Met-168 residue in penicillin acylase from Kluyvera citrophila was changed to Ala by oligonucleotide site-directed mutagenesis. The Ala-168 mutant exhibited different substrate specificity than wild-type and enhanced thermal stability. The thermodynamic profiles for penicillin G hydrolysis catalyzed by both enzymes were obtained from the temperature dependence of the steady-state kinetic parameters Km and kcat. The high values of enthalpy and entropy of activation determined for the binding of substrate suggest that an induced-fit-like mechanism takes place. The Met----Ala168 mutation unstabilizes the first transition-state (E..S not equal to) and the enzyme-substrate complex (ES) causing a decrease in association equilibrium and specificity constants in the enzyme. However, no change is observed in the acyl-enzyme formation. It is concluded that residue 168 is involved in the enzyme conformational rearrangements caused by the interaction of the acid moiety of the substrate at the active site. PMID- 2306470 TI - Immunological characterization of constitutive isozymes of cytochrome P-450 from rainbow trout. Evidence for homology with phenobarbital-induced rat P-450s. AB - Immunoglobulin G fractions (IgGs), isolated from rabbits immunized against hepatic cytochrome P-450 isozymes were used to investigate the immunochemical homology among trout P-450s and between trout and rat P-450s. The antigens used for immunization were five constitutive trout P-450s (LMC1 to LMC5), one beta naphthoflavone (BNF)-inducible trout P-450 (LM4b), and one phenobarbital-induced rat P4500IIB1 (PB-B). In the enzyme-linked immunosorbent assay (ELISA), strong cross-reactivity was observed between anti-LMC2 IgG and P-450 LMC1, and between anti-LMC3 IgG and P-450 LMC4. There was little or no cross-reactivity of anti LMC5 IgG with other trout P-450s. Trout P-450 LM4b was not recognized by any of the antibodies against constitutive trout P-450s. Antibodies to P-450 LMC1 and P450 LMC2 cross-reacted strongly with rat P450IIB1 and with proteins of PB induced rat liver microsomes. Rat P450IA1 (BNF-B) did not cross-react with anti LMC1 or anti-LMC2 IgG. These cross-reactions were essentially confirmed by immunoblot (Western blot) analysis. Western blots of PB-induced rat liver microsomes probed with anti LMC1 revealed two major immunoreactive proteins in the P-450 region, one of which co-migrated with rat P450IIB1. P450IIB1 itself cross-reacted strongly with anti-LMC1 IgG. In control rats, a single protein band cross-reacted poorly with anti-LMC1 IgG. Antibodies to LMC1 and LMC2 did not cross-react with rat P450IA1 in Western blots. The antigenic epitopes in rat P450IIB1 recognized by anti-LMC1 IgG and anti-LMC2 IgG are probably not located at or near the active site of the enzyme since these antibodies did not inhibit benzphetamine N-demethylase activity of P450IIB1 or of PB-induced rat liver microsomes. In general, our results demonstrate: (1) the presence of a significant homology between LMC1 and LMC2, and between constitutive trout P-450 (LMC1) and PB-induced rat P-450 (P450IIB1); and (2) distant homology between constitutive trout P-450s and constitutive rat P-450s or BNF-induced rat P-450s. PMID- 2306471 TI - Presence of functional domains in Limulus polyphemus hemocyanin. AB - In an attempt to isolate structural domains of arthropod hemocyanins and possibly to investigate their functional properties, we have undertaken proteolytic digestion experiments of isolated subunits from Panulirus interruptus and Limulus polyphemus oxy-hemocyanin. Satisfactory results have been obtained using trypsin at high concentration and short digestion times. Results show that, in the case of Panulirus hemocyanin, only subunit alpha is susceptible to trypsin digestion, but that proteolytic cleavage is associated with the loss of the copper-oxygen band; on the other hand, in the case of Limulus hemocyanin, four subunits (I, II, III and IV) show a significant susceptibility to trypsin, and their fragmentation takes place with preservation of the oxygen-binding capacity. A more detailed study of the digestion products of subunit IV from Limulus hemocyanin reveals that the proteolytic fragments keep together in a single non-covalent complex. Attempts to separate the native fragments result in the precipitation of the digestion products. Subunit IV of Limulus with proteolytic cuts binds O2 and CO with the same affinity as the native subunit, suggesting that the copper site is still preserved structurally and is functionally active in a 37 kDa trypsin resistant domain. PMID- 2306472 TI - Relationships among the subunits of the high molecular weight proteinase, macropain (proteasome). AB - An analysis of the subunits of the high molecular weight proteinase, macropain (multicatalytic proteinase or proteasome) from human erythrocytes has been conducted using N-terminal amino acid sequencing, gel electrophoresis and reverse phase peptide mapping. This analysis provided evidence for the existence of 13 subunits of different primary structure. Five subunits were susceptible to the Edman degradation and yielded unique N-terminal sequences. Similarities among these sequences, however, indicated that the subunits are homologous. Two dimensional gel electrophoresis discriminated 10 major components, which included two of the subunits for which N-terminal sequences had been determined and eight N-terminally blocked subunits. Tryptic peptide mapping indicated that all 10 of these components have a different amino acid sequence. Tryptic peptides from some of the subunits were subjected to amino acid sequence analysis, and the data indicated that all the subunits tested in this way are related by common ancestry. The data suggest that at least nine of the total of 13 subunits are encoded by members of the same gene family; the remaining four subunits have not yet been investigated in sufficient detail to establish their relationships. No evidence for a close relationship with any previously investigated proteinase family has been found. Finally, through a comparison of the 'latent' and 'active' forms of macropain, the study established a close similarity in the subunit composition of these catalytically very different species, although proteolytic degradation of selected subunits appears in the active form of the enzyme. PMID- 2306473 TI - Total hydrolysis of proteins with strongly reduced racemization of amino acids. AB - A new method has been devised for the complete hydrolysis of proteins with an extremely low level of racemization of amino acids. Proteins are incubated in 10 M HCl at a low temperature to obtain partial hydrolysis. They are then incubated with pronase and finally with leucine aminopeptidase and peptidyl-D-amino-acid hydrolase from Loligo vulgaris. The proposed method ensures the total hydrolysis of either purified proteins or proteins contained in a crude homogenate of animal or vegetable tissue. In both cases, the racemization of amino acids (expressed as rate of D form/D + L form X 100) was lower than 0.015% for aspartic acid and lower than 0.01% for other amino acids. D-Amino acids released from peptides or proteins were estimated with enzymatic methods based on the use of octopus D aspartate oxidase or hog kidney D-amino acid oxidase; with these enzymes, 0.05 nmol of a D-amino acid was determined in the presence of up to 20 mumols of a mixture of L-amino acids (ratio %D/D + L = 0.00025). The method allows the determination of D-amino acids either in tissues in which they are present in high concentrations (as human cataract lenses, tooth enamel, etc.) or in those with low enantiomer content (as brain, erythrocytes, etc.). Using the method described, we hydrolyzed several synthetic peptides consisting of D- and L-amino acids and determined the amount of D-amino acids. In addition, we totally hydrolyzed all the nuclear proteins of human cataractous lenses. The amount of D aspartic acid was 0.026 mumols/mg in lenses of women aged between 71 and 76 years and 0.0256 mumols/mg in lenses of men aged between 55 and 72 years. The D aspartic acid measured corresponds to about 12% with respect to total aspartic acid. PMID- 2306474 TI - The alpha and pi isoenzymes of glutathione S-transferase in human fetal lung: in utero ontogeny compared with differentiation in lung organ culture. AB - Polyclonal antisera to the alpha and pi isoenzymes of glutathione S-transferase have been used in immunohistochemical studies of developing human lung. In utero expression of the pi set was down-regulated in distal airway cells and the first appearance of pi-negative cells coincided with phenotypic differentiation. In contrast, in the early phase of fetal lung organ culture pi isoenzyme was detected in all differentiated epithelial cells and only as culture progressed did focal negativity develop. The alpha set showed no developmental changes in utero or in organ culture. PMID- 2306475 TI - Inhibition of dopamine beta-hydroxylase by bidentate chelating agents. AB - 1-2H-Phthalazine hydrazone (hydralazine; HYD), 2-1H-pyridinone hydrazone (2 hydrazinopyridine; HP), 2-quinoline-carboxylic acid (QCA), 1 isoquinolinecarboxylic acid (IQCA), 2,2'-bi-1H-imidazole (2,2'-biimidazole; BI), and 1H-imidazole-4-acetic acid (imidazole-4-acetic acid; IAA) directly and reversibly inhibit homogeneous soluble bovine dopamine beta-hydroxylase (3,4 dihydroxyphenethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1). HYD, QCA and IAA show competitive allosteric inhibition of dopamine beta-hydroxylase with respect to ascorbate (Kis = 5.7(+/- 0.9) microM, 0.14(+/- 0.03) mM, 0.80(+/- 0.20) mM; nH = 1.4(+/- 0.1), 1.8(+/- 0.4), 2.8(+/- 0.6), respectively). HYD and IAA show slope and intercept mixed-type allosteric inhibition of dopamine beta-hydroxylase with respect to tyramine. QCA shows allosteric uncompetitive inhibition of dopamine beta-hydroxylase with respect to tyramine. HP, BI and IQCA all show linear competitive inhibition (Kis = 1.9(+/- 0.3) microM, 21(+/- 6) microM, and 0.9(+/- 0.3) microM, respectively) with respect to ascorbate. HP and BI show linear mixed-type while IQCA shows linear uncompetitive inhibition of dopamine beta-hydroxylase with respect to tyramine. In the presence of HP, HYD or IAA intersecting double-reciprocal plots of the initial velocity as a function of tyramine concentration at differing fixed levels of ascorbate are observed. These findings are consistent with a uni-uni ping-pong-ter-bi kinetic mechanism for dopamine beta-hydroxylase that involves a ternary enzyme-ascorbate-tyramine-oxygen complex. The results for HYD, QCA and IAA are the first examples of allosteric inhibitor interactions with dopamine beta-hydroxylase. PMID- 2306476 TI - Inactivation of dopamine beta-hydroxylase by p-cresol: evidence for a second, minor site of covalent modification at tyrosine 357. AB - p-Cresol is a mechanism-based inhibitor of bovine dopamine beta-hydroxylase (3,4 dihydroxyphenethylamine, ascorbate: oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1) (DBH) which covalently modifies a tyrosine at position 216 during inactivation (DeWolf, W.E., Jr., Carr, S.A., Varrichio, A., Goodhart, P.J., Mentzer, M.A., Roberts, G.D., Southan, C., Dolle, R.E. and Kruse, L.I. (1988) Biochemistry 27, 9093-9101). Here we report the recovery and characterization of additional minor peptides that are produced during the inactivation of DBH with p [3H]cresol. Sequence and structural analysis of these peptides indicates tyrosine 357 as a second, minor site of modification. PMID- 2306477 TI - Inhibition of plant calcium-dependent protein kinases by basic polypeptides. AB - Wheat embryo Ca2+-dependent protein kinase (CDPK) is inhibited by a variety of polypeptides including actin, gramicidin S, melittin, protamine, various histone preparations, histone H4 and by basic amino-acid homopolymers. Melittin (Ki 9 microM) is a non-competitive inhibitor of wheat germ CDPK and also inhibits wheat leaf CDPK and silver beet leaf CDPKs. Protamine inhibits wheat germ CDPK in an apparently competitive fashion (Ki 0.2 microM) and is also a potent, albeit less effective, inhibitor of the leaf CDPKs. Various basic amino-acid homopolymers are also potent, apparently competitive inhibitors of wheat embryo CDPK, namely poly(L-lysine) (IC50 2 nM), poly(L-ornithine) (IC50 3 nM) and poly(L-arginine) (IC50 17 nM) and also inhibit the leaf CDPKs, albeit at higher concentrations. Histone H4 and various calf thymus histone preparations inhibit wheat embryo CDPK in a fashion that is not competitive and calmodulin can substantially reverse such inhibition. PMID- 2306478 TI - Regulation of apolipoprotein gene expression and plasma high-density lipoprotein composition in experimental nephrosis. AB - Hepatic and intestinal RNA levels were measured in rats made nephrotic by injection of puromycin aminonucleoside (PAN). The following increases in hepatic RNA levels, relative to controls, were measured: poly A+ (1.2), ribosomal (1.2), mRNA levels for transferrin (1.8), albumin (3.8) apolipoprotein (apo)E (2.3), apoB (2.5), apoA-II (1.9) and apoA-I (6.1). Increases of 1.5- to 2.2-fold in hepatic mRNA levels for albumin, apoA-II, apoB and apoE were measured in pre nephrotic animals killed before the onset of proteinuria. Intestinal RNA levels in pre-nephrotic and nephrotic animals were not significantly different from control values. Transcription of the hepatic apoA-I gene increased 1.8-fold in nephrotic animals compared to controls. Immunological detection of apolipoproteins in high-density lipoproteins (HDL) separated by gradient gel electrophoresis indicated an increase in apoA-I and a decrease in apoA-IV and apoE containing HDL particles in nephrosis. To simulate the effects of increased apoA-I gene expression, human apoA-I was added to rat plasma in vivo and in vitro. ApoE was displaced from HDL by increased concentration of apoA-I. The results indicate that relatively small changes in apoA-I levels in the serum lead to significant changes in the apolipoprotein composition of HDL. PMID- 2306479 TI - Determination of the presence of ceramide aminoethylphosphonate and ceramide N methylaminoethylphosphonate in marine animals by fast atom bombardment mass spectrometry. AB - Phosphonosphingolipids from 15 kinds of shellfish were analyzed by fast atom bombardment mass spectrometry to determine the contents of ceramide aminoethylphosphonate (CAEPn) and ceramide N-methylaminoethylphosphonate (CMAEPn). Two pairs of ions, at m/z 126 and 140 in the positive ion mode and at m/z 124 and 138 in the negative ion mode, were used to distinguish between aminoethylphosphonic acid and N-methylaminoethylphosphonic acid in CAEPn and CMAEPn. Interestingly, mollusca in the early stage of evolution have both CAEPn and CMAEPn, while most in the middle stage have only CMAEPn and those in the highest stage have only CAEPn. PMID- 2306480 TI - Accumulation of ceroid-like pigments in macrophages cultured with phosphatidylcholine liposomes in vitro. AB - When mouse peritoneal macrophages as well as P388D1 cells, an established macrophage-like cell line, were cultured with liposomes composed of rat liver phosphatidylcholine and phosphatidylserine, storage of fluorescent products, ceroid-like pigments, within those cells was observed with light and fluorescence microscopy, and fluorescence spectrophotometry. The amounts of thiobarbituric acid-reactive substances and fluorescent products in macrophages were increased gradually to reach a maximal level to between 6 and 8 days of culture. The involvement of peroxidation of liposomal lipids in the formation of the pigments was further suggested by the 6 days that incorporation of alpha-tocopherol into liposomes decreased the storage of the pigments. No appreciable formation of the pigments was observed in macrophages cultured with liposomes containing dipalmitoylphosphatidylcholine instead of rat liver phosphatidylcholine. The fluorescent products formed in cultured cells were found in lipid-soluble and insoluble fractions. Lipid-insoluble fluorescent products had an excitation maximum at 360 nm and a fluorescence maximum at 430 nm in SDS-aqueous solution (pH 7.4) and the intensity of the fluorescence was quenched at base pH, but it was not changed in acidic media. These findings indicate that the macrophages can store Schiff base fluorescent substances formed by the reaction between peroxidation products of exogenous lipids and amino compounds in the cells, under some pathological conditions. PMID- 2306481 TI - Changes in the activities of dihydroxyacetone phosphate and glycerol-3-phosphate acyltransferases in rat liver under various conditions. AB - Activities of enzymes relating to the acyl dihydroxyacetone phosphate (acyl DHAP) pathway were determined in rat liver under conditions known to elevate the peroxisomal beta-oxidation activity. In fasted and streptozotocin-induced diabetic rats, DHAP acyltransferase activity showed a small but significant increase, though the activities of glycerol-3-phosphate (GP) acyltransferase and alkyl DHAP synthase were not changed. After 2 weeks, feeding of 20% partially hydrogenated marine oil, the activity of DHAP acyltransferase also increased to 140% of the control. The feeding of 0.25% clofibrate and 2% di(2 ethylhexyl)phthalate (DEHP) increased the activities of both DHAP and GP acyltransferases by 2- to 3-fold, whereas alkyl DHAP synthase activity decreased under the same conditions. A fractionation study showed that the increases in the activities of DHAP acyltransferase and acyl/alkyl DHAP reductase in the liver of rats treated with DEHP occurred mainly in peroxisomes and microsomes, respectively. The phospholipid contents per mg protein of the isolated hepatic peroxisomes from rats were as follows (percent of the control): fasting, 62%; diabetic, 69%; high fat-diet, 89%; clofibrate-treated, 126%; DEHP-treated, 119%. These results suggest that glycerophospholipid metabolism might also be controlled by peroxisomal enzymes under physiological and pathological conditions. PMID- 2306482 TI - Studies on the lecithin: cholesterol acyltransferase substrate properties of HDL as determined by its subclass distribution analysed by gradient gel electrophoresis. AB - In order to study the impact of high-density lipoproteins (HDL) subclasses on the ability of HDL to act as substrate for lecithin: cholesterol acyltransferase (LCAT), we isolated HDL from nine normolipidemic male subjects. The HDL particle size distribution was analysed by gradient gel electrophoresis and the esterification rate of the isolated homologous HDL was compared with a pool of HDL where all the nine subjects took part. It was found that the strongest determinant for HDL cholesterol esterification rate was the inhibitory action of HDL subclass 2B. PMID- 2306483 TI - Mycolic acid synthesis by Mycobacterium aurum cell-free extracts. AB - The first cell-free system capable of synthesizing whole mycolic acids: (R1CH(OH)CH(R2)COOH, with 60 to 90 carbon atoms) from [1-14C]acetate is described and preliminary investigations into some of its requirements and properties are reported. Biosynthetic activity for mycolic acids occurred in an insoluble fraction (40 000 X g pellet) from disrupted cells of Mycobacterium aurum (ATCC 23366-type strain); it produced mycolic acids, but a very small amount of non hydroxylated fatty acids. The predominant product was unsaturated mycolic acid (type I), while oxo- (type IV) and dicarboxy- (type VI) mycolic acids were synthesized to a lesser extent. When [1-14C]palmitic acid was used as a marker, no labelled mycolic acid was detected. The reaction required a divalent cation (Mg2+ or Mn2+), KHCO3 and O2. Neither CoA, NADH, NADPH nor ATP were necessary, but CoA rather increased the synthesis of non-hydroxylated fatty acids. Glucose or trehalose were not required. Avidin inhibited the biosynthesis of the three types of mycolic acid indicating the presence of a biotin-requiring enzyme in the reaction sequence and therefore a carboxylation step, but citrate had no allosteric effect. Iodoacetamide inhibited the system. These first data are in favor of a complex multienzyme system. PMID- 2306484 TI - Polyunsaturated fatty acid profiles and alpha-tocopherol levels in plasma and whole blood incubated with copper. Evidence of inhibition of lipoperoxidation in plasma by hemolysate. AB - Polyunsaturated fatty acid (PUFA) profiles and alpha-tocopherol levels were studied in human plasma and whole blood incubated with copper under air or nitrogen. In plasma, both PUFAs and alpha-tocopherol disappeared. The results were completely different in whole blood: (i) in plasma, while alpha-tocopherol decreased in the same manner as in plasma incubated alone, profiles of PUFA were only slightly modified. So, in spite of the absence of alpha-tocopherol, lipoperoxidation was not very marked. That is why the release of a protective factor from erythrocytes during hemolysis was under consideration. This was confirmed by the complete inhibition of degradation of PUFAs in plasma when hemolysate was added; (ii) In erythrocytes, no modification in PUFA profiles could be detected while alpha-tocopherol decreased slightly. Thus, not only do erythrocytes resist the copper-dependent oxidative stress in an incredible manner, but they also seem to protect plasma at the time of hemolysis. PMID- 2306485 TI - 2-(7,13-Dihydroxy-2-trans-octadecenoylamino)ethanesulfonic acid (lipotaurine) as an intermediate of taurolipids biosynthesis. AB - A hydroxy fatty-acid-combined taurine (lipotaurine) was found in the taurolipids fraction of Tetrahymena thermophila. Lipotaurine accounted for about 1.4% of the total taurolipids of the cells, and was composed of taurine and 7,13-dihydroxy-2 trans-octadecenoic acid. By nuclear magnetic resonance, mass and infrared spectrometries, the chemical structure of lipotaurine was identified as 2-(7,13 dihydroxy-2-trans-octadecenoylamino)ethanesulfonic acid. When cells of T. thermophila were incubated with the double-labeled lipotaurine which was biosynthesized from [2(n)-3H]taurine and [1-14C]stearic acid, both the radioactivities were detected in taurolipid A, B and C. Furthermore, the ratio of the radioactivities of 3H and 14C in the lysotaurolipids were the same as that of the lipotaurine. From these results, it is suggested that lipotaurine is an intermediate of taurolipid biosynthesis. PMID- 2306486 TI - Augmentation of LDL receptor activities on lymphocytes by interleukin-2 and anti CD3 antibody: a flow cytometric analysis. AB - Dormant lymphocytes are known to show little LDL receptor (LDL-R) activities. The present study was designed to determine whether or not LDL-R activities of lymphocytes from normal subjects were high enough to be measured by flow cytometry after the cells had been stimulated with recombinant interleukin-2 (IL 2) and anti-CD3 monoclonal antibody (mAb). IL-2 or anti-CD3 mAb individually provokes proliferation of lymphocytes in a serum-free medium. Proliferation rate was accelerated when the two reagents were used in combination. Stimulated cells cultured for 5 days expressed more than 85% CD3 positive, less than 0.5% CD14 positive, and less than 1.5% CD20 positive. The LDL-R activities of the cells were examined by the uptake of a fluorescence probe, DiI-labeled LDL (DiI-LDL) and analyzed by flow cytometry. Stimulated cells showed increased uptake of DiI LDL and 84 +/- 9% were positive, whereas only 3.0 +/- 2.5% of the cells without stimulation were positive (P less than 0.001). Under the same conditions stimulated lymphocytes from a homozygous familial hypercholesterolemia (FH) patient showed little LDL-R activities; 14% of the cells were positive. Displacement assays reveal that the uptake of LDL by these cells is occurring by way of its specific pathway. These data imply the lymphocytes stimulated with the reagents used in the study might be used for detecting defects in LDL-R, perhaps defects in other genomic systems as well. PMID- 2306487 TI - Effect of drugs which inhibit cholesterol synthesis on syncytia formation in vero cells infected with measles virus. AB - We found that nontoxic doses of two inhibitors of cholesterol synthesis, namely W 7 and cerulenin, delayed syncytia formation in vero cells infected with measles virus. To correlate syncytia formation and lipidic membrane changes induced by these drugs, we labelled cell lipids with [14C]acetate. Measles virus infection increased the incorporation of radiolabel into fatty acids, triacylglycerol, cholesterol ester, and decreased its incorporation into cholesterol and 1,2 diacylglycerol. The ratios phosphatidylcholine/sphingomyelin and free cholesterol/lanosterol-dihydrolanosterol also decreased during the infection. W-7 and cerulenin greatly altered lipid metabolism. Both decreased the phosphatidylcholine to sphingomyelin and the cholesterol to lanosterol dihydrolanosterol ratios. Z-D-Phe-L-Phe-L-Gly, a tripeptide which corresponds to the N-terminal sequence of the viral fusion protein (responsible for syncytia formation) and which inhibits virus-induced cell fusion without affecting virus synthesis also perturbed cholesterol metabolism. The tripeptide reversed the phosphatidylcholine to sphingomyelin ratio in infected cells. At non-toxic doses, W-7 inhibited the synthesis of infectious virus. Cerulenin which inhibited strongly the lipid synthesis did not. Finally, the well characterized inhibitors of cholesterol synthesis, mevinolin, ketoconazole and miconazole were shown to inhibit the syncytia formation. We conclude that the inhibition of syncytia by W 7 and cerulenin is associated with their capacity to alter the cholesterol metabolism, whereas the antiviral effect of W-7 does not seem related to this capacity. PMID- 2306488 TI - Regulation of LTP-I secretion from human monocyte-derived macrophages by differentiation and cholesterol accumulation in vitro. AB - Human macrophages in vitro synthesize and secrete the cholesteryl ester (CE) transfer protein, LTP-I. The effect of differentiation of monocyte-to-macrophage on the synthesis and secretion of LTP-I cholesteryl ester transfer activity was investigated. One marker of macrophage differentiation is expression of the 'scavenger' receptor, which mediates macrophage uptake and degradation of acetylated low-density lipoprotein. Monocytes secreted very little detectable CE transfer activity in the first 24 h following cell isolation. Both CE transfer activity and scavenger receptor activity increased with time in culture. Thus, although circulating monocytes probably do not secrete CE transfer activity, tissue macrophages such as hepatic Kupffer cells may contribute to plasma CE transfer activity. Resident macrophages of the arterial wall are derived from circulating monocytes which enter the vessel wall where they differentiate into macrophages. Such macrophages are the principal source of lipid-laden foam cells of the atherosclerotic plaque. Cholesterol accumulation results when uptake of lipoprotein cholesterol overwhelms the capacity of macrophages to excrete cholesterol. Since LTP-I is postulated to function in reverse cholesterol transport, the effect on LTP-I secretion of loading macrophages with cholesterol was determined after exposure of macrophages to acetylated-LDL or free cholesterol (FC). Cholesterol loading by both these maneuvers resulted in dose dependent increases in macrophage secretion of CE transfer activity, and there was a significant positive correlation between CE transfer activity secreted and accumulation of CE. Thus, LTP-I may function at the cellular level in maintenance of lipid homeostasis: macrophage LTP-I secretion may be a protective mechanism in response to excess cholesterol accumulation in resident macrophages of the arterial wall. PMID- 2306489 TI - The effect of chylomicron remnants on bile acid synthesis in cultured rat hepatocytes. AB - The effect of chylomicron remnants on bile acid synthesis in isolated rat hepatocytes in monolayer cultures was investigated. Production of bile acids by the cells in the presence of chylomicron remnants at a cholesterol concentration of 7.8-9 nmol/ml was increased by approx. 75% after 17 h and 25% after 24 h incubation. Similar concentrations of cholesterol added to the cells in the form of chylomicrons had no significant effect on bile acid synthesis. These results suggest that cholesterol taken up in chylomicron remnants may be an important source of substrate for bile acid synthesis. PMID- 2306490 TI - Effectors of hemoglobin. Separation of allosteric and affinity factors. AB - The relative contributions of the allosteric and affinity factors toward the change in p50 have been calculated for a series of effectors of hemoglobin (Hb). Shifts in the ligand affinity of deoxy Hb and the values for 50% ligand saturation (p50) were obtained from oxygen equilibrium data. Because the high affinity parameters (liganded conformation) are poorly determined from the equilibrium curves, they were determined from kinetic measurements of the association and dissociation rates with CO as ligand. The CO on-rates were obtained by flash photolysis measurements. The off-rates were determined from the rate of oxidation of HbCO by ferricyanide, or by replacement of CO with NO. The partition function of fully liganded hemoglobin for oxygen and CO is only slightly changed by the effectors. Measurements were made in the presence of the effectors 2,3-diphosphoglycerate (DPG), inositol hexakisphosphate (IHP), bezafibrate (Bzf), and two recently synthesized derivatives of Bzf (LR16 and L35). Values of p50 change by over a factor of 60; the on-rates decrease by nearly a factor of 8, with little change in the off-rates for the liganded conformation. The data indicate that both allosteric and affinity parameters are changed by the effectors; the changes in ligand affinity represent the larger contribution toward shifts in p50. PMID- 2306491 TI - Relationships between lipid membrane area, hydrophobic thickness, and acyl-chain orientational order. The effects of cholesterol. AB - A microscopic interaction model for a fully hydrated lipid bilayer membrane containing cholesterol is used to calculate, as a function of temperature and composition, the membrane area, the membrane hydrophobic thickness, and the average acyl-chain orientational order parameter, S. The order parameter, S, is related to the first moment, M1, of the quadrupolar magnetic resonance spectrum which can be measured for lipids with perdeuterated chains. On the basis of these model calculations as well as recent experimental measurements of M1 using magnetic resonance and of membrane area using micromechanical measurements, a discussion of the possible relationships between membrane area, hydrophobic thickness, and moments of nuclear magnetic resonance spectra is presented. It is pointed out that S under certain circumstances may be useful for estimating the hydrophobic membrane thickness. This is particularly advantageous for multicomponent membranes where structural data are difficult to obtain by using diffraction techniques. The usefulness of the suggested relationships is demonstrated for cholesterol-containing bilayers. PMID- 2306492 TI - Cholesterol dynamics in membranes. AB - Time-resolved fluorescence anisotropy of the sterol analogue, cholestatrienol, and 13C nuclear magnetic resonance (NMR) spin lattice relaxation time (T1c) measurements of [13C4] labeled cholesterol were exploited to determine the correlation times characterizing the major modes of motion of cholesterol in unsonicated phospholipid multilamellar liposomes. Two modes of motion were found to be important: (a) rotational diffusion and (b) time dependence of the orientation of the director for axial diffusion, or "wobble." From the time resolved fluorescence anisotropy decays of cholestatrienol in egg phosphatidylcholine (PC) bilayers, a value for tau perpendicular, the correlation time for wobble, of 0.9 x 10(-9) s and a value for S perpendicular, the order parameter characterizing the same motion, of 0.45 s were calculated. Both tau perpendicular and S perpendicular were relatively insensitive to temperature and cholesterol content of the membranes. The T1c measurements of [13C4] labeled cholesterol did not provide a quantitative determination of tau parallel, the correlation time for axial diffusion. T1c from the lipid hydrocarbon chains suggested a value for tau perpendicular similar to that for cholesterol. Steady state anisotropy measurements and time-resolved anisotropy measurements of cholestatrienol were used to probe sterol behavior in a variety of pure and mixed lipid multilamellar liposomes. Both the lipid headgroups and the lipid hydrocarbons chains contributed to the determination of the sterol environment in the membrane, as revealed by these fluorescence measurements. In particular, effects of the phosphatidylethanolamine (PE) headgroup and of multiple unsaturation in the lipid hydrocarbon chains were observed. However, while the steady-state anisotropy was sensitive to these factors, the time-resolved fluorescence analysis indicated that tau perpendicular was not strongly affected by the lipid composition of the membrane. S perpendicular may be increased by the presence of PE. Both steady-state anisotropy measurements and time-resolved anisotropy measurements of cholestatrienol were used to probe sterol behavior in three biological membranes: bovine rod outer segment (ROS) disk membranes, human erythrocyte plasma membranes, and light rabbit muscle sarcoplasmic reticulum membranes. In the ROS disk membranes the value for S perpendicular was marginally higher than in the PC membranes, perhaps reflecting the influence of PE. The dramatic difference noted was in the value for tau perpendicular. In both the ROS disk membranes and the erythrocyte membranes, tau perpendicular was one-third to one-fifth of tau perpendicular in the phospholipid bilayers. This result may reveal an influence of membrane proteins on sterol behavior. PMID- 2306493 TI - Earliest mechanical evidence of cross-bridge activity after stimulation of single skeletal muscle fibers. AB - The stiffness of single fibers from frog skeletal muscle was measured by the application of small 2-kHz sinusoidal length oscillations during twitch and tetanic contractions at a range of initial sarcomere lengths. The earliest mechanical signs of activation were a fall in tension (latency relaxation) and a rise in stiffness. The earliest stiffness increase and the earliest tension fall occurred simultaneously at all sarcomere lengths. This suggests a cross-bridge origin for the latency relaxation. The lead of stiffness over tension seen during the rise of tension was substantially established during the latent period. Reducing the size of the twitch by reducing calcium release with D-600 (methoxyverapamil) reduced the latency relaxation and the stiffness development during latency much less than it reduced the twitch tension. For very small twitches the peak of the stiffness response occurred during the latent period and the times of onset of both latency relaxation and stiffness rise were delayed, but remained coincident. This suggests a strong connection between the latency relaxation and the rise of stiffness during the latent period, whereas the connection between these events and positive tension generation appears to be less strong. PMID- 2306494 TI - Global parameter optimization for cardiac potassium channel gating models. AB - Quantitative ion channel model evaluation requires the estimation of voltage dependent rate constants. We have tested whether a unique set of rate constants can be reliably extracted from nonstationary macroscopic voltage clamp potassium current data. For many models, the rate constants derived independently at different membrane potentials are not unique. Therefore, our approach has been to use the exponential voltage dependence predicted from reaction rate theory (Stevens, C. F. 1978. Biophys. J. 22:295-306; Eyring, H., S. H. Lin, and S. M. Lin. 1980. Basic Chemical Kinetics. Wiley and Sons, New York) to couple the rate constants derived at different membrane potentials. This constrained the solution set of rate constants to only those that also obeyed this additional set of equations, which was sufficient to obtain a unique solution. We have tested this approach with data obtained from macroscopic delayed rectifier potassium channel currents in voltage-clamped guinea pig ventricular myocyte membranes. This potassium channel has relatively simple kinetics without an inactivation process and provided a convenient system to determine a globally optimized set of voltage dependent rate constants for a Markov kinetic model. The ability of the fitting algorithm to extract rate constants from the macroscopic current data was tested using "data" synthesized from known rate constants. The simulated data sets were analyzed with the global fitting procedure and the fitted rate constants were compared with the rate constants used to generate the data. Monte Carlo methods were used to examine the accuracy of the estimated kinetic parameters. This global fitting approach provided a useful and convenient method for reliably extracting Markov rate constants from macroscopic voltage clamp data over a broad range of membrane potentials. The limitations of the method and the dependence on initial guesses are described. PMID- 2306495 TI - Oligomerization and conformation change in solutions of calf lens gamma II crystallin. Results from 1/T1 nuclear magnetic relaxation dispersion profiles. AB - From analyses of the magnetic field dependence of 1/T1 (nuclear magnetic relaxation dispersion [NMRD] profiles) of water protons in solutions of highly purified calf lens gamma II-crystallin, we find that monomers form oligomers at relatively low concentrations, which increase in size with increasing concentration and decreasing temperature. At approximately 16% by volume and -4 degrees C, the mean oligomeric molecular weight is approximately 120-fold greater than the monomeric value of 20 kD. Below this concentration, there is no indication of any substantive change in conformation of the monomeric subunits. At higher concentrations, the tertiary structure of the monomer appears to reconfigure rather abruptly, but reversibly, as evidenced by the appearance of spectra-like 14N peaks in the NMRD profiles. The magnitudes of these peaks, known to arise from cross-relaxation of water protons through access to amide (NH) moieties of the protein backbone, indicate that the high concentration conformation is not compact, but open and extended in a manner that allows enhanced interaction with solvent. The data are analogous to those found for homogenates of calf and chicken lens (Beaulieu, C. F., J. I. Clark, R. D. Brown III, M. Spiller, and S. H. Koenig. 1988. Magn. Reson. Med. 8:47-57; Beaulieu, C. F., R. D. Brown III, J. I. Clark, M. Spiller, and S. H. Koenig. 1989. Magn. Reson. Med. 10:62-72). This unusually large dependence of oligomeric size and conformation on concentration in the physiological range is suggested as the mechanism by which osmotic equilibrium is maintained, at minimal metabolic expense, in the presence of large gradients of protein concentration in the lens in vivo (cf Veretout and Tardieu, 1989. Eur. Biophys. J. 17:61-68). Finally, the results of the NMRD data provide a ready explanation of the low temperature phase transition, and "cold-cataract" separation of phases, observed in gamma II crystallin solutions; we suggest that the phases that separate are the two major conformers detected by NMRD. PMID- 2306496 TI - Abnormal ryanodine receptor channels in malignant hyperthermia. AB - Previous studies have demonstrated a defect associated with the calcium release mechanism of sarcoplasmic reticulum (SR) from individuals susceptible to malignant hyperthermia (MH). To examine whether SR calcium release channels were indeed altered in MH, SR vesicles were purified from normal and MH susceptible (MHS) porcine muscle. The Ca2+ dependence of calcium efflux rates from 45Ca2(+) filled SR vesicles was then compared with the Ca2+ dependence of single-channel recordings of SR vesicles incorporated into planar lipid bilayers. The rate constants of 45Ca2+ efflux from MHS SR were two to threefold larger than from normal SR over a wide range of myoplasmic Ca2+. Normal and MHS single channels were progressively activated in a similar fashion by cis Ca2+ from pCa 7 to 4. However, below pCa 4, normal channels were inactivated by cis Ca2+, whereas MHS channels remained open for significantly longer times. The altered Ca2+ dependence of channel inactivation in MHS SR was also evident when Ca2+ was increased on the trans side while cis Ca2+ was held constant. We propose that a defect in a low-affinity Ca2+ binding site is responsible for the altered gating of MHS SR channels. Such a defect could logically result from a mutation in the gene encoding the calcium release channel, providing a testable hypothesis for the molecular basis of this inherited disorder. PMID- 2306497 TI - Effects of modifications of the retinal beta-ionone ring on archaebacterial sensory rhodopsin I. AB - Ring desmethyl and acyclic analogues of all-trans retinal were incorporated into the apoprotein of the phototaxis receptor sensory rhodopsin I (SR-I) in Halobacterium halobium membranes. All modified retinals generate SR-I analogue pigments which exhibit "opsin shifts," i.e., their absorption spectra are shifted to longer wavelengths compared with model protonated Schiff bases of the same analogues. Each SR-I pigment analogue exhibits cyclic photochemical reactions as monitored by flash spectroscopy, but the analogue photocycles differ from that of native SR-I by exhibiting pronounced biphasic recovery of flash-induced absorption changes and abnormal flash-induced absorption difference spectra. Despite perturbations in the photochemical properties, the SR-I pigment analogues are capable of both attractant (single photon) and repellent (two photon) phototaxis signaling in cells. Our interpretation is that the hydrophobic ring substituents interact with the binding pocket to maintain the correct configuration for native SR-I absorption and photochemistry, but these interactions are not essential for the physiological function of SR-I as a dual attractant/repellent phototaxis receptor. These results support the conclusion emerging from several studies that the photoactivation process that triggers the conformation changes of SR-I and the related proton pump bacteriorhodopsin is conserved despite the different biological functions of their photoactivation. PMID- 2306498 TI - A versatile model of steady state O2 supply to tissue. Application to skeletal muscle. AB - A model of combined convective and diffusive O2 transport to tissue is suggested which allows for the calculation of PO2 distributions in a cuboid tissue region with arbitrary microvascular geometries and blood flows. Carrier-facilitated O2 diffusion in the erythrocytes and in the tissue and red blood cell reaction kinetics are considered. The model is based on analytical descriptions of the PO2 fields of single erythrocytes surrounded by carrier-free layers in an infinite three-dimensional space containing an O2 carrier such as myoglobin. These PO2 fields are overlaid to obtain a solution of the differential equation of diffusion in respiring tissue. The model has been applied to a situation in heavily working skeletal muscle. Resulting PO2 profiles exhibit steep peri capillary PO2 gradients. Further into the fiber, the profiles are essentially flat at low PO2 levels in good agreement with experimental findings (Gayeski and Honig. 1986. Am. J. Physiol. 251:H789-H799). PO2 dependence of facilitation of O2 transport produces a "layer deficient of functional carrier" which extends into the muscle fiber and which represents a reserve of O2 conductance automatically recruited in exercise. Furthermore, it results in a homogenization of red blood cell O2 fluxes which accounts for the absence of PO2 gradients along the muscle fiber axis (cf. Gayeski and Honig. 1988. Am. J. Physiol. 254: H1179-H1186). PMID- 2306499 TI - Mechanisms of intracellular ice formation. AB - The phenomenon of intracellular freezing in cells was investigated by designing experiments with cultured mouse fibroblasts on a cryomicroscope to critically assess the current hypotheses describing the genesis of intracellular ice: (a) intracellular freezing is a result of critical undercooling; (b) the cytoplasm is nucleated through aqueous pores in the plasma membrane; and (c) intracellular freezing is a result of membrane damage caused by electrical transients at the ice interface. The experimental data did not support any of these theories, but was consistent with the hypothesis that the plasma membrane is damaged at a critical gradient in osmotic pressure across the membrane, and intracellular freezing occurs as a result of this damage. An implication of this hypothesis is that mathematical models can be used to design protocols to avoid damaging gradients in osmotic pressure, allowing new approaches to the preservation of cells, tissues, and organs by rapid cooling. PMID- 2306500 TI - Vibrational fluctuations of hydrogen bonds in a DNA double helix with nonuniform base pairs. AB - The Green's function technique is applied to a study of breathing modes in a DNA double helix which contains a region of different base pairs from the rest of the double helix. The calculation is performed on a G-C helix in the B conformation with four consecutive base pairs replaced by A-T. The average stretch in hydrogen bonds is found amplified around the A-T base pair region compared with that of poly(dG)-poly(dC). This is likely related to the A-T regions lower stability against hydrogen bond melting. The A-T region may be considered to be the initiation site for melting in such a helix. PMID- 2306501 TI - A model of the muscarinic receptor-induced changes in K(+)-current and action potentials in the bullfrog atrial cell. AB - A model is formulated for characterizing the behavior of the acetylcholine (ACh) sensitive K+ membrane channel (muscarinic channel) in bullfrog atrial myocytes. Parameters of the muscarinic current model are chosen in fit available data from the literature on bullfrog atrial myocytes (3, 4, 45). This model is subsequently incorporated into a large mathematical model of the bullfrog myocyte that is based on quantitative whole-cell voltage clamp data (40). Simulations are conducted on the active atrial cell model in bathing media containing ACh at different concentrations to explore the effect of this muscarinic channel on the electrical behavior of the myocyte. The model predicts a progressive shortening of the action potential with increasing [ACh], as well as an indirect influence of the muscarinic K+ current on the other membrane currents of the atrial cell. Interpretation of the simulation results provides suggestions for the probable mechanisms underlying the shortening of the action potential due to activity of the muscarinic channel. Specifically, the model predicts that with an increase in ACh concentration: (a) the outward muscarinic current, IK,ACh(t), increases in magnitude but shortens in duration; (b) the calcium current, ICa(t), may increase in magnitude, but when it does so it decreases in duration compared with the control conditions; (c) the intracellular Ca2+ concentration [Ca2+]i waveform during the action potential decreases in both magnitude and duration. Because the contractile activity of the cell is controlled by the [Ca2+]i waveform, the model predicts a decrease in contractile strength with an increase in ACh concentration in the bathing medium; i.e., a negative inotropic effect. PMID- 2306502 TI - Multilayer adsorption of lysozyme on a hydrophobic substrate. AB - Macromolecular adsorption is known to occur as a complex process, often in a series of steps. Several models are discussed in the literature which describe the microscopic structure of the adsorbate. In the present study we investigated the adsorption of hen egg white lysozyme on alkylated silicon oxide surfaces. A combination of fluorescence excitation in the evanescent field and fluorescence recovery after photobleaching allowed us to measure the amount of adsorbed fluorescent lysozyme and the equilibrium exchange kinetics with molecules in solution. We found that a model with at least three classes of adsorbed molecules is necessary to describe the experimental results. A first layer is formed by the molecules which adsorb within a short time after the beginning of the incubation. These molecules make up approximately 65% of the final coverage. They are quasi irreversibly adsorbed and do not measurably exchange with bulk molecules within one day even at temperatures up to 55 degrees C. A second layer, which reaches equilibrium only after several hours of incubation, shows a pronounced exchange with bulk molecules. The on-off kinetics show a distinct temperature dependence from which an activation barrier of delta E approximately 22 kcal/mol is derived. A third layer of molecules that exchange rapidly with the bulk can be seen to comprise approximately 10% of the total coverage. The exchange rate is on the order of fractions of a second. The binding of the latter two classes of adsorbed molecules is exothermic. From the temperature dependence of the coverage, the binding enthalpy of the slowly exchanging layer was estimated to be delta Hads approximately 3.8 kcal/mol. The second and third class of molecules remain enzymatically active as a muramidase, which was tested by the lysis of the cell walls of Micrococcus lysodeiktikus. The molecules in the first layer, on the other hand, showed no enzymatic activity. PMID- 2306503 TI - Return current in encephalography. Variational principles. AB - The encephalographic problem of finding the electric potential V and the return current associated with any assumed primary current, Jp, is put in the form of a variational principle. With Jp and the conductivity specified, the correct V is one which makes an integral quantity P[V] a maximum. The terms in P[V] are related to the rates at which work is done by the electric field on the primary and return currents. It is shown that there is a unique solution for the electric field, and it satisfies the conservation of energy; this condition can serve as a check on any numerical solution. With the conductivity a different constant in different regions, the variational principle is recast in terms of the charge density on the surfaces of discontinuity. An iteration-variation method for finding the solution is outlined, and possible computational advantages over other approaches are discussed. PMID- 2306504 TI - Elastic behavior of zymogen granule membranes in response to changes in pH and pCa. AB - In the process of secretion, the membrane of secretory granules is expected to change its elastic behavior. Elastic modulus of the membrane of zymogen granules, prepared from the rat pancreas acinar cell, was measured by an osmotic swelling method. The elastic modulus of the granule membrane at pCa 8 reduced from the maximal value of 230 dyn/cm at pH 6.0 to almost zero at pH 7.5. In a cytosol of an acinar cell, calcium ions play an important role as a second messenger in secretion. The elastic modulus of the granule membrane reduced in a sigmoidal fashion at pCa between 7.0 and 6.0. This range of pCa corresponds to a physiological rise of free Ca2+ concentrations in the cell cytosol when stimulated by external secretagogues. Reduction of the elastic modulus indicates that the state of the granule membrane switches to a more flexible one in which the granule is easy to appose to the cell plasma membrane and then swell as a final step of exocytosis. PMID- 2306505 TI - Effect of solute permeability in determination of elastic modulus using the vesicular swelling method. AB - The modulus of elasticity of artificial and biological membranes can be determined in membrane vesicles by monitoring the limitation of vesicular swelling during a slow decrease in medium tonicity. The higher the elastic modulus of the membrane, the more effectively the vesicles will resist swelling. This method assumes that the solutes in the system are impermeant, so that the final volume of the vesicles is determined solely by a balance of osmotic and hydrostatic forces. In this paper, we present the results of computer simulation of vesicular swelling in which the solute permeability of the membrane was varied. We find that even a small permeability will lead to a loss of solute from the vesicle that will retard the increase in vesicular volume during dilution of the medium, and thereby cause the apparent modulus of elasticity to be much greater than the true value. For example, if one takes the mannitol permeability in brush border membrane vesicles from small intestine to be 0.004 micron/s (a reasonable estimate), one finds that a vesicular swelling study using mannitol as the principal solute will show the apparent elastic modulus of the vesicles to be greater than 10 times larger than the true value. With higher permeabilities, the effect is even more dramatic. We conclude that determination of impermeance of solutes is a critical prerequisite for making valid determinations of membrane elastic modulus using the vesicular swelling method. PMID- 2306506 TI - Volume expansion of nonmyelinated nerve fibers during impulse conduction. AB - Nonmyelinated nerve fibers undergo rapid volume expansion while carrying an impulse. This volume expansion is incurred as a consequence of a lateral expansion of the excited portion of the fibers, where the superficial layer is transformed into a low-density structure. PMID- 2306507 TI - P-31 nuclear magnetic resonance studies of the appearance of an isotropic component in dielaidoylphosphatidylethanolamine. AB - We have utilized phosphorus nuclear magnetic resonance, which provides an excellent means of characterizing the physical state of lipids, to investigate the polymorphic phase behavior of pure dielaidoylphosphatidylethanolamine (DEPE). We have observed a sharp isotropic component in the typical bilayer and inverted hexagonal P-31 NMR spectra. This component appears in the spectra of both the bilayer and inverted hexagonal lipid phases after several cycles through the bilayer-to-hexagonal phase transition. The magnitude of the isotropic component increased as a function of the number of cycles through the transition. The appearance of this component was not a function of time at constant temperature, but only a function of the number of cycles through the transition. The isotropic component is stable at all temperatures above the gel-to-liquid crystal transition, but it abruptly disappears when the lipid is cooled below the gel-to liquid crystal phase transition. It is suggested that this isotropic phase is similar to the isotropic phase observed in dioleoylphosphatidylethanolamine (DOPE) by x-ray diffraction and identified as a cubic phase (Shyamsunder, E., S. M. Gruner, M. W. Tate, D. C. Turner, P. T. C. So, and C. P. S. Tilcock. 1988. Biochemistry. 27:2332-2336). PMID- 2306508 TI - Covalent cross-linking of single fibers from rabbit psoas increases oscillatory power. AB - Single fibers from chemically skinned rabbit psoas muscle were treated with 1 ethyl-3-[3-dimethyl-amino)proyl]-carbodiimide (EDC) at 20 degrees C after rigor was induced. A 22-min treatment resulted in 18% covalent cross-linking between myosin heads and the thin filament as determined by stiffness measurements. This treatment also results in covalent cross-linking among rod portions of myosin molecules in the backbone of the thick filament. The fibers thus prepared are stable and do not dissolve in solutions at ionic strengths as high as 1,000 mM. The preparation was subjected to sinusoidal analysis, and the resulting complex modulus data were analyzed in terms of three exponential processes, (A), (B), and (C). Oscillatory work (process B) was much greater in the cross-linked fibers than in untreated ones in activating solutions of physiological ionic strength (200 mM); this difference was attributed to the decline of process (A) with EDC treatment. Consequently, the Nyquist plot of the EDC-treated preparation exhibited an insect-type response. We conclude that, under these conditions, both cross-linked and non-cross-linked myosin heads contribute to the production of oscillatory power. The cross-linked preparations also exhibited oscillatory work in high ionic strength (500-1,000 mM) solutions, indicating that cross-linked myosin heads are capable of utilizing ATP to produce work. We conclude that process (A) does not relate to an elementary step in a cross-bridge cycle, but it may relate to dynamics outside the cross-bridge such as filament sliding or sarcomere rearrangement. PMID- 2306509 TI - High-resolution electron density profiles reveal influence of fatty acids on bilayer structure. AB - Small-angle x-ray diffraction studies were performed on gel phase-oriented bilayers of dipalmitoylphosphatidylcholine (DPPC) and DPPC containing 40 mol% of either palmitic acid (PA) or palmitic acid brominated at the 2-position (BPA). Oriented samples were prepared using a method developed by us, which is as simple as powder sample preparations while offering all the advantages of oriented samples made by traditional methods. Phases were determined using swelling experiments with structure factors plotted in reciprocal space, creating a relatively smooth curve as the amount of water between the bilayers was changed. Continuous Fourier transforms were also calculated to further test the consistency of the phase assignments. The diffraction data were used to calculate absolute electron density profiles for different bilayers to a resolution of 5-6 A. Analysis indicates the following: (a) The electron density profiles for the three preparations are virtually identical in the hydrocarbon chain region. (b) There is a decrease in the electron density of the glycerol backbone-headgroup region and d-space in DPPC-PA compared to DPPC. (c) The bromine of fatty-acid brominated at the 2-position is in the vicinity of the glycerol backbone. (d) The bilayer thickness of DPPC containing either brominated or unbrominated fatty acid remains relatively constant with increased levels of hydration, unlike DPPC bilayers. PMID- 2306510 TI - Theoretical basis for an anomalous temperature coefficient in swelling pressure of rabbit corneal stroma. AB - In the rabbit corneal stroma, the swelling pressure, P, has been reported to have an anomalous (negative) temperature coefficient, alpha P, contradicting traditional Donnan swelling theory. A parallel-plate, diffuse double layer Gouy Chapman model was used to resolve this discrepancy. The present model incorporates the possibility that surface charge, sigma, is temperature dependent. It is shown that negative, zero, or positive coefficients of swelling pressure change with temperature are not mutually exclusive conditions, but can be attributed to the same underlying mechanism. For likely values of alpha P(range -7 x 10(-3) K-1 to +3.2 x 10(-3)K-1), the effective stromal charge has a negative temperature dependency, or dln sigma/dT less than 0. The present formalism is robust against variation in assumed alpha P, and is able to simultaneously satisfy the known values of swelling pressure, its thermal dependency, and stromal charge. These results implicate significant coulombic forces behind P. Predicted stromal surface charge is approximately 0.01 Cm-2. The predictions were confirmed with macrocontinuum Donnan swelling theory, suggesting that Donnan osmotic swelling is the principal macroscopic component of P. PMID- 2306511 TI - Magnetic field of a single muscle fiber. First measurements and a core conductor model. AB - We present the first measurements of the magnetic field from a single muscle fiber of the frog gastrocnemius, obtained by using a toroidal pickup coil coupled to a room-temperature, low-noise amplifier. The axial currents associated with the magnetic fields of single fibers were biphasic and had peak-to-peak amplitudes ranging between 50 and 100 nA, depending primarily on the fiber radius. With an intracellular microelectrode, we measured the action potential of the same fiber, which allowed us to determine that the intracellular conductivity of the muscle fiber in the core conductor approximation was 0.20 +/- 0.09 S/m. Similarly, we found that the effective membrane capacitance was 0.030 +/- 0.011 F/m2. These results were not significantly affected by the anisotropic conductivity of the muscle bundle. We demonstrate how our magnetic technique can be used to determine the transmembrane action potential without penetrating the membrane with a microelectrode, thereby offering a reliable, stable, and atraumatic method for studying contracting muscle fibers. PMID- 2306512 TI - Two-dimensional recognition pattern of lipid-anchored Fab' fragments. AB - A two-dimensional pattern of oriented antibody fragments was formed at the air water interface and transferred onto a solid support. The Fab'-fragments of a monoclonal antibody against the hapten dinitrophenyl (DNP) were covalently linked via a hydrophilic spacer to phospholipid vesicles. A monomolecular lipid-protein layer at equilibrium with these vesicles was allowed to form at the air-water interface. The monolayer was separated from the vesicle phase and transferred to a Langmuir-Blodgett trough. By cooling and compressing, the previously homogeneous lipid-protein film was driven into a two-dimensional phase separation resulting in protein-rich domains and a second phase consisting mainly of lipid. This film was transferred onto a solid support in a way that preserved the protein-lipid pattern. The specificity as well as the contrast in the binding activity of the two different separated phases were then quantified using microfluorometry. DNP conjugated to fluorescein-labeled bovine serum albumin (BSA) showed virtually no binding to the lipid regions, but gave a ratio of bound DNP-BSA to Fab'-lipid of greater than 50% in the protein-rich domains proving that the Fab'-moiety retained its biological activity. This demonstrates that the technique presented here is well suited to modify different solid surfaces with a pattern of a given biological function. The optional control of lateral packing and orientation of the components in the monolayer makes it a general tool for the reconstitution of supported lipid-protein membranes and might also open new ways for the two-dimensional crystallization of proteins at membranes. PMID- 2306513 TI - On the modulation of a high-enthalpy pretransition in binary mixtures of DMPC and DMPG by polar headgroup interaction. AB - Employing high-sensitivity differential scanning calorimetry (DSC), we discovered a pretransition in binary mixtures of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, the main feature of which is its extraordinarily high transition enthalpy of 6.3 Kcal/mol, nearly an order of magnitude higher than those values previously found for such transitions. Using DSC, deuterium nuclear magnetic resonance, and electron microscopy, it is shown that the energetic origin of this type of pretransition is caused by interactions between the phospholipids in their headgroup region. The most likely interaction involves the formation of a hydrogen bond between the headgroups of the two phospholipid species in the gel (L beta') phase which is disrupted at the transition to the "ripple" (P beta') phase. The finding that this large pretransition is unique for mixtures of phosphocholine and phosphoglycerol with myristoyl chains indicates a dependence of the headgroup long range order of such mixtures in the gel phase on the acyl chain length. PMID- 2306514 TI - Factor VIIa-catalyzed activation of factor X independent of tissue factor: its possible significance for control of hemophilic bleeding by infused factor VIIa. AB - Infusing factor VIIa (FVIIa) has been reported to control bleeding in hemophilic patients with factor VIII (FVIII) inhibitors. This is difficult to attribute to an enhanced FVIIa/tissue factor (TF) activation of factor X, since in vitro studies suggest that infusion of FVIIa should neither increase substantially the rate of formation of FVIIa/TF complexes during hemostasis (Proc Natl Acad Sci USA 85:6687, 1988) nor bypass the dampening of TF-dependent coagulation by the extrinsic pathway inhibitor (EPI) (Blood 73:359, 1989). Partial thromboplastin times have also been reported to shorten after infusion of FVIIa. The experiments reported herein establish that shortening of partial thromboplastin times after adding FVIIa to hemophilic plasma in vitro stems from an FVIIa-catalyzed activation of factor X independent of possible trace contamination of reagents with TF. Experiments in purified systems confirmed that FVIIa can slowly activate factor X in a reaction mixture containing Ca2+ and phospholipid but no source of TF. The rate of activation was sufficient to account for the shortening of partial thromboplastin times observed. EPI, which turned off continuing FVIIa/TF activation of factor X, was unable to prevent continuing FVIIa/phospholipid activation of factor X. Because circulating plasma contains only a trace, if any, free FVIIa, such a reaction could never occur physiologically. However, infusing FVIIa creates a nonphysiologic circumstance in which a continuing slow FVIIa/phospholipid catalyzed activation of factor X could conceivably proceed in vivo unimpeded by EPI. Such a mechanism of factor X activation might compensate for an impaired factor IXa/FVIIIa/phospholipid activation of factor X during hemostatis, and therefore control bleeding in a hemophilic patient. PMID- 2306515 TI - Induction of platelet Ca2+ influx and mobilization by a monoclonal antibody to CD9 antigen. AB - We found that a monoclonal antibody (MoAb) to CD9 antigen, PMA2, induced a rise in cytosolic free calcium concentration ([Ca2+]i) in fura-2-loaded platelets, and we examined whether this response was due to direct action of PMA2 on CD9 antigen. The rise in [Ca2+]i was dependent on the PMA2 concentration, irrespective of the presence or absence of extracellular Ca2+. The role of secreted adenosine diphosphate (ADP) and thromboxane in the [Ca2+]i response to PMA2 was studied using creatine phosphate/creatine phosphokinase (CP/CPK) and aspirin. Combined treatment with CP/CPK and aspirin abolished the rise in [Ca2+]i, although either CP/CPK or aspirin alone produced only partial inhibition. Inhibition of adenosine triphosphate (ATP) secretion and thromboxane B2 synthesis by an MoAb to the glycoprotein IIb-IIIa complex, PMA1, resulted in little [Ca2+]i response to PMA2. In contrast, thrombasthenic platelets, in which ATP secretion and thromboxane B2 synthesis were normal, showed a normal [Ca2+]i response. When PMA2 was added to CD9+ mononuclear cells, no rise in [Ca2+]i was observed. Thus, we conclude that binding of monoclonal immunoglobulin G molecules to the CD9 antigen raises [Ca2+]i through the effect of secreted ADP and thromboxane on platelets, and that CD9 antigen is not directly involved in induction of Ca2+ influx and mobilization. PMID- 2306516 TI - Factor IX New London: substitution of proline for glutamine at position 50 causes severe hemophilia B. AB - We describe a novel point mutation in the fourth exon of human factor IX (encoding the first EGF-like domain) in which cytosine is substituted for adenosine at position 10,401, resulting in the substitution of proline for glutamine at position 50 in the polypeptide chain. Sequence analysis of all eight exons, all exon-intron junctions, 160 base pairs (bp) of DNA 5' to the proposed translation start site, and 60 bp 3' to the translation termination site shows no other difference from the normal factor IX gene, with the exception of a previously described benign polymorphism at position 148 in the protein (Ala--- Thr). The affected subject has severe hemophilia B with no detectable factor IX activity despite normal factor IX antigen levels. We purified the abnormal factor IX by immunoaffinity chromatography and demonstrated that its activation by factor Xla is markedly delayed compared with normal factor lX. Once activated, the abnormal factor lX binds antithrombin III in a 1:1 molar ratio, and the activated protein demonstrates catalytic activity, suggesting an intact active site. The mutation creates a new Bst Yl restriction endonuclease cleavage site. Restriction with Bst Yl shows the mutation in maternal DNA and offers the possibility of direct carrier status analysis and prenatal diagnosis in kindreds with this mutation. We designate this new mutation factor lXNew London. This is the only reported mutation in the first EGF-like domain that causes severe hemophilia B. PMID- 2306517 TI - Human platelet osteonectin: release, surface expression, and partial characterization. AB - Our laboratory has previously shown that osteonectin, an abundant noncollagenous bone protein, is contained in and secreted from human platelets. In this study, the distribution of osteonectin both in the supernatant and on the platelet surface after activation was measured by fluid-phase and solid-phase radioimmunoassay, respectively. Total cellular osteonectin was determined by RIA of guanidinium chloride extracted platelets and ranged from 0.65 to 2.2 micrograms/10(8) platelets or 135,000 to 457,000 molecules/platelet. Platelets treated with varying concentrations of collagen and thrombin released osteonectin in a dose-dependent fashion. Approximately 61% of the total platelet osteonectin was secreted at saturating concentrations of collagen and thrombin. A small fraction of platelet osteonectin is expressed on the surface of platelets in an activation-specific manner as evidenced by the specific and saturable binding of [125I]-anti-osteonectin monoclonal antibody, IIIA3A8, to thrombin-activated platelets. Based on a non-linear least squares regression analysis of the antibody binding, 2,200 IIIA3A8 molecules, or 0.8% of the total platelet osteonectin, is expressed on the platelet surface on activation. Platelet osteonectin was purified from the supernatant of thrombin-activated platelets by immunoaffinity chromatography. Western blotting of proteins secreted by washed, thrombin-stimulated platelets with IIIA3A8 indicated that the osteonectin molecule released from the platelet is a single chain polypeptide. Comparison of immunopurified platelet osteonectin with isolated bovine bone osteonectin and isolated human bone osteonectin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that platelet osteonectin has a greater apparent molecular weight than bone osteonectin. The NH2-terminal sequence of immunopurified platelet osteonectin was obtained by automated Edman degradation and is identical to the sequence of human bone osteonectin derived from the cDNA of SaOS-2 cells. Collectively, these data suggest that platelet osteonectin is structurally distinct from bone osteonectin in a region of the molecule at a distance from the NH2-terminus. PMID- 2306518 TI - Effects of interleukin-4 on the in vitro growth of human lymphoid and plasma cell neoplasms. AB - Recombinant human interleukin-4 (rhIL-4) has pleiotropic biologic effects including stimulation of normal B-cell growth. We investigated the effects of rhIL-4 on the in vitro growth of 35 fresh human lymphoid and plasma cell malignancies. Inhibition of growth was seen in 52% and 60% of multiple myeloma and lymphoma specimens, respectively. Growth was stimulated relative to control in 8.6% (3 of 35) of the tumors tested. Immunophenotyping showed that tumors displaying growth stimulation expressed surface markers associated with a poor clinical prognosis. Our findings support the clinical evaluation of rhIL-4 as a therapeutic agent in selected patients with lymphoid and plasma cell neoplasms. PMID- 2306519 TI - Detection of non-Hodgkin's lymphoma in the peripheral blood by analysis of antigen receptor gene rearrangements: results of a prospective study. AB - Analysis of immunoglobulin (Ig) and T-cell receptor gene rearrangements, using Southern blot hybridization, has been applied to peripheral blood lymphocytes (PBL) in 335 samples from patients with non-Hodgkin's lymphoma. The incidence of circulating lymphoma cells detected by gene rearrangement analyses is related to the histologic subtype, clinical stage of disease, and clinical status. Among 104 patients studied at diagnosis, the incidence of positive analyses was 34% in low grade lymphoma and only 8% in intermediate-grade lymphoma. Clonal Ig gene rearrangements were detected nearly universally in the small lymphocytic histologic subtype. PBL studies were related to the initial stage of disease: positive studies were seen in 35% of patients with stage IV disease, 29% of patients with stage III disease, and 12% of patients with stages I-II disease. The incidence of PBL rearrangements at the time of disease recurrence in 32 patients requiring cytoreductive therapy was 48%, somewhat greater than at initial diagnosis. A group of patients with low-grade lymphoma, who had treatment deferred after diagnosis or recurrence, was also studied; the incidence of PBL rearrangements was 38% in this population. Among 157 patients clinically free of disease, DNA analyses of the PBL were positive in only 10%. Subsequent relapse of disease in 26 patients was antedated by PBL rearrangement in only one patient. Clonal rearrangements detected in 15 patients have been followed by recurrence of clinical disease in only one patient over a median of 24 months from the time of analysis. The lack of detectable rearrangements in the peripheral blood in the majority of patients may be due to methodology or the biology of the disease. These issues may be further addressed with alternative methods for assessment of minimal disease. However, rigorous testing of any new molecular tool requires an adequate patient population in which disease status is closely monitored over a sufficient period of time. PMID- 2306520 TI - T lymphocytes from invaded lymph nodes in patients with B-cell-derived non Hodgkin's lymphoma: reactivity toward the malignant clone. AB - Tumor-infiltrating T lymphocytes (TIL-T) are always present in B-cell-derived non Hodgkin's lymphoma (NHL). In this investigation, we explored the possibility that collaboration might exist between these cells. TIL-T were isolated from 39 lymph nodes of patients with NHL. In most of the cases, few of them (less than 10%) possessed surface activation receptors CD25 or OKT9. In 80% of the cases, they proliferated in response to recombinant interleukin-2 (rIL-2), but the degree of proliferation was often low as compared with control populations. The influence of irradiated autologous malignant cells on the TIL-T proliferation in response to rIL-2 (40 U/mL) was also investigated: in 38% of the cases, this proliferation was not modified (group O), and in 41% it was higher (group +) and in 21% it was lower (group -). The mechanism of this immune response (specific or not) is not elucidated at present. The definition of these groups was statistically correlated with different parameters of the disease: (1) percentage of TIL-T was higher in group + (44% +/- 17%) than in group O (31% +/- 18%) and group - (24% +/ 15%); (2) B-cell proliferation in centrofollicular lymphomas was more frequently nodular or nodular and diffuse in group + (83%) and O (55%) than in group - (0%); (3) low-grade malignancies in the Working Formulation were more frequent in group + (75%) than in group O (60%) or group - (12%); (4) favorable prognosis evaluated with the Grenoble cytologic classification was more frequent in group + and O (87%) than in group - (12%); (5) actuarial survival curves showed a significantly better prognosis for patients in group +. PMID- 2306521 TI - Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid less than 45 line. AB - Cytogenetic and DNA flow cytometric analyses of leukemic cells from 2,184 children with newly diagnosed acute lymphoblastic leukemia (ALL) identified 27 cases (1.2%) that had a hypodiploid line with fewer than 45 chromosomes per cell. Had cytogenetic techniques been used alone, seven cases would have been missed, compared with five if only flow cytometry had been used. For comparative purposes, the 27 cases were divided into three groups: near-haploid (n = 10), hypodiploid 30-40 (n = 9), and hypodiploid 41-44 (n = 8). Blast cells from patients with near-haploid ALL lacked structural chromosomal abnormalities; showed nonrandom retention of two copies of chromosomes 8, 10, 14, 18, 21, and the sex chromosomes; and had a second leukemic line with exactly twice the number of chromosomes or DNA content. Karyotypic analysis of the hypodiploid 30-40 and hypodiploid 41-44 groups disclosed structural abnormalities in the stemline or sideline of most of the well-banded cases; those in the latter group were similar to findings in cases with 45 chromosomes. As in the near-haploid group, chromosome 21 and the sex chromosomes were preferentially retained in the hypodiploid 30-40 and 41-44 cases. Except for a slight excess of female patients in the near-haploid group and an older age at diagnosis in the hypodiploid 30-40 cases, there were no initial clinical features that distinguished these patients from the general ALL population. Despite intensive treatment and short follow-up, 17 of the 27 patients have relapsed. This study suggests that the poor treatment responsiveness of hypodiploid ALL is not limited to the more than 80% of the patients who have 45 chromosomes per leukemic cell and demonstrates that cytogenetic and flow cytometric analyses are complementary in the evaluation of children with ALL. PMID- 2306522 TI - Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow. AB - We report our experience from a clinical trial of autologous bone marrow transplantation (ABMT) in the treatment of 30 patients with acute myeloid leukemia (AML) using monoclonal antibody (MoAb) and complement-treated bone marrow. All patients were in complete remission (CR) at the time of transplant: 6 patients were in first CR, 18 in second CR, and 6 in third CR. The median age of all patients was 42 years (range 11 to 57 years). For marrow ablation, 28 patients were treated with cyclophosphamide and total body irradiation. One patient was treated with busulfan and cyclophosphamide and one was treated with busulfan and VP-16. Each patient was then transfused with autologous bone marrow that had been harvested previously and treated with two MoAbs, PM-81 and AML-2 23, and rabbit complement. Median time to recovery of neutrophils (500/microL) was 30 days, and platelets (20,000/microL) was 45 days. Median time for initial erythrocyte engraftment, assessed by a flow cytometric reticulocyte assay, was 13 days. Median overall and relapse-free survival of first CR patients was at least 17.4 months post-ABMT and the 2- and 3-year actuarial overall and relapse-free survival was 67% (+/- 19%). Median survival for the 24 patients in second or third CR was 6.8 months post-ABMT and 9.3 months since CR; however, six patients survived disease-free from 16 to 61 months post-ABMT. For the second and third CR group it was observed that six patients (5 of the 6 survivors) showed "inversions," when their post-ABMT remission lasted longer than any previous one. Actuarial 2- and 3-year disease-free and overall survival of patients in second and third CR was 25% (+/- 9%) and 18% (+/- 9%), and 29% (+/- 9%) and 23% (+/- 9%), respectively. ABMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation. PMID- 2306523 TI - A new single nucleotide change at the initiation codon (ATG----AGG) identified in amplified genomic DNA of a Chinese beta-thalassemic patient. PMID- 2306524 TI - Assessment of human exposure to atrazine through the determination of free atrazine in urine. PMID- 2306525 TI - Residue analysis of triadimefon, triadimenol, and the BAY KWG 1342 diol and BAY KWG 1323 hydroxylated metabolites in winter wheat. PMID- 2306526 TI - Effect of colloidal soil components on the adsorption of mevinphos. PMID- 2306527 TI - Levels of transaminases in tissues of the penaeid prawn, Metapenaeus monoceros (Fabricius) following sublethal kelthane exposure. PMID- 2306528 TI - Occurrence and seasonal variation of heavy metals in the oyster Saccrostrea iridescens. PMID- 2306529 TI - Nitrosamines in formulations of deet and EPTC. PMID- 2306530 TI - Life table evaluation of the effects of cadmium exposure on the freshwater cladoceran, Moina macrocopa. PMID- 2306531 TI - Heavy metals in the eastern oyster, Crassostrea virginica, of the Mississippi sound. PMID- 2306532 TI - Cadmium uptake and toxicity to water hyacinth: effect of repeated exposures under controlled conditions. PMID- 2306533 TI - Heavy metal concentrations in a lichen of Mt. Rainier and Olympic National Parks, Washington, USA. PMID- 2306534 TI - Accumulation of Am-241 and Cm-244 from water and sediments by Hyalella sp. and Tubifex spp. PMID- 2306535 TI - Genotoxic effects of erioflorin acetate and erioflorin methacrylate: sesquiterpene lactones isolated from Podanthus ovatifolius lag. (Compositae). PMID- 2306536 TI - Assessment of di- and tri-butyltin interaction with skeletal muscle membranes. PMID- 2306537 TI - Disposition of perfluorooctanoic acid in the rat after single and subchronic administration. PMID- 2306538 TI - Fate of dietary cadmium at two intake levels in the odonate nymph, Aeshna canadensis. PMID- 2306539 TI - Use of Selenastrum capricornutum and Microfeast as food for Daphnia pulex. PMID- 2306540 TI - Survival of northern bobwhites in Georgia: cropland use and pesticides. PMID- 2306541 TI - Measurement of ATV applicator exposure to atrazine using an ELISA method. PMID- 2306542 TI - Survey for pesticides in wells associated with apple and peach orchards in West Virginia. PMID- 2306544 TI - Removal of organophosphorus, organochlorine and synthetic pyrethroid insecticides and organochlorine fungicides from coverall fabric by laundering. PMID- 2306543 TI - Residues of 1-naphthol in soil and water samples in and around Bhopal, India. PMID- 2306545 TI - Determination of Senecio alkaloids by thermospray liquid chromatography/mass spectrometry. AB - A series of Senecio alkaloid and alkaloid N-oxide standards has been analyzed using positive and negative ion thermospray liquid chromatography/mass spectrometry (LC/MS) with an ammonium acetate-containing mobile phase. On-line separations of pyrrolizidine alkaloids from extracts of Senecio jacobaea (tansy ragwort) and Senecio vulgaris (common groundsel) were done using an ammonium hydroxide-containing mobile phase. All of the alkaloids known to be present in the extracts were detected by ammonium hydroxide thermospray LC/MS, as well as many other components which may be as-yet-unidentified alkaloids. PMID- 2306546 TI - Determination of the primary structure of peptides using fast atom bombardment mass spectrometry. AB - The determination of the amino acid composition and sequence of a peptide, using both conventional and tandem fast atom bombardment mass spectrometry, is presented. First a list of potential empirical formulae is generated using the accurate mass and isotopic peak intensity ratios from the molecular ion cluster. The formulae are mathematically analyzed to ensure that they correspond to linear peptides composed of 19 common amino acids. Then using the ions below m/z 160 Da, which are characteristic of the amino acid content of the peptide, the formulae are decomposed into possible amino acid compositions. From each composition sequences are generated and their predicted fragment ions are compared to ions present in the mass spectrum. A score based on the intensities and the occurrence of consecutive sequence fragments is calculated. Finally sequences with the ten highest scores are retained. Analyses performed on typical peptides with molecular weights below 1500 Da indicate that identification can generally be achieved using this approach. PMID- 2306547 TI - Measurement of ethyl carbamate in blood by capillary gas chromatography/mass spectrometry using selected ion monitoring. AB - Methodology is presented for convenient, reproducible and direct measurement of blood concentrations of ethyl carbamate, an experimental animal carcinogen. Extraction techniques requiring 20 microliters of blood and selected ion monitoring using ethyl (13C, 15N)carbamate as internal standard enabled quantification of ethyl carbamate concentrations ranging from 50 ng ml-1 to 100 micrograms ml-1. Coefficients of variation at several representative concentrations averaged less than 4%. The method was used to determine the time course of elimination of ethyl carbamate from mice receiving doses of 125 mumol kg-1. PMID- 2306548 TI - High-performance liquid chromatography/tandem mass spectrometry: its use for the identification of stanozolol and its major metabolites in human and equine urine. AB - A screening procedure for the anabolic steroid stanozolol in human and equine urine was developed based on enzymatic hydrolysis, liquid-liquid extraction and reversed-phase liquid chromatography combined on-line with tandem mass spectrometry. The column effluent was introduced into the atmospheric pressure ionization source of a triple-quadrupole mass spectrometer via a heated pneumatic nebulizer liquid chromatograph/mass spectrometer interface. Abundant protonated molecular ions were generated by corona discharge ionization. Confirmation of stanozolol and several of its hydroxylated and dihydroxylated metabolites isolated from both human and equine urine was accomplished by collision-induced dissociation of their parent ions. Interpretation of the daughter ion mass spectra gave valuable information for the structural elucidation of the detected metabolites. Using the selected reaction monitoring detection mode the presence of the urinary excretion products could be monitored in equine urine up to one day and in human urine for several days after oral administration of stanozolol. Microbore high-performance liquid chromatography/ion spray mass spectrometry of an ion-pair extract enabled the direct detection of intact sulfoconjugated hydroxy-metabolites in human urine. PMID- 2306549 TI - Characterization of photo-induced pyrimidine cyclobutane dimers by laser desorption Fourier transform mass spectrometry. AB - Laser desorption Fourier transform mass spectrometry was used to characterize the cis-syn cyclobutane photodimers of uracil-uracil, uracil-thymine and thymine thymine. This soft ionization technique generated [M-H]- ions as well as some fragment ions. Investigation of the laser desorption process indicated that gas phase dimerization reactions do not occur for pyrimidine monomers and dimers under these experimental conditions. Collisional dissociation of the [M-H]- ions provided structural information for the pyrimidine rings of the dimers. The fragment ions observed in the collisional dissociation spectra of these cyclobutane dimers suggested rearrangement of the [M-H]- parent ions to a macrocycle prior to dissociation. PMID- 2306550 TI - Quantitative measurement of clenbuterol at the femtomole level in plasma and urine by combined gas chromatography/negative ion chemical ionization mass spectrometry. AB - A highly sensitive and specific assay was developed for the quantitative measurement of clenbuterol at the femtomole level in human plasma and urine. Clenbuterol and the internal standard (2H9)clenbuterol were measured by gas chromatography/negative ion chemical ionization mass spectrometry with methane as the reagent gas. The two compounds of interest were extracted from the biological samples at pH 13 using ethyl acetate. After two subsequent purification steps, the cleaned-up organic extract was derivatized with pentafluoropropionic anhydride. The mass spectrometer was set to monitor the abundant [M-HCl]- ions of the perfluoroacyl derivatives (m/z 368 and 377), which were generated in the ion source by an electron capture process. This assay required 1 ml of plasma or 0.5 ml of urine and the detection limit of the method was 5 pg ml-1 with a 12.8% relative standard deviation. The accuracy of the clenbuterol assay was also tested day to day with quality control specimens spiked blind to the analyst. The mean difference between the theoretical and actual values was lower than 4.1%. PMID- 2306551 TI - Bone mass in young patients with type I diabetes. AB - We measured bone mineral content (BMC) with single photon absorptiometry in two groups of young patients with type I diabetes: the first group (prospective study) consists of 48 patients followed from onset to the third year of diabetes and the second group (cross-sectional study) consists of 66 long-term diabetics. Bone mineral content at onset of disease was lower than normal in only two cases. After 3 years of diabetes no male revealed BMC below the normal range but two females (6.6%) had low BMC values. In our cross-sectional study we found a BMC reduction in 12% of the cases. We did not find a relationship between bone deficit and duration of diabetes, or bone mass values and HbA1. PMID- 2306552 TI - A comparison of biochemical indices of bone turnover in elderly institutionalized and free-living subjects. AB - Plasma concentrations of calcium-phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25(OH)D) and albumin, and fasting urinary sodium/creatinine (Na/Cr), calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (HPr/Cr) were measured in a survey of 208 Chinese elderly subjects living in chronic care institutions, and compared with values from free-living elderly subjects. Plasma parathyroid hormone estimations were also performed on a subpopulation of women living in an institution. Subjects in institutions had higher urinary HPr/Cr ratios in both men and women, as well as higher urinary Ca/Cr ratios in women, suggesting increased bone resorption. These values show significant variation depending on the degree of mobility. Factors which could contribute to the increased bone loss among institutionalized subjects are: reduced physical activity, reduced exposure to sunlight and hence reduced plasma 25(OH)D concentrations, low calcium intake, protein calorie malnutrition and possibly higher sodium intake. Correction of these factors may reduce the risk of fractures among the elderly living in chronic care institutions. PMID- 2306553 TI - Bone loss in response to long-term glucocorticoid therapy. AB - A number of studies have shown that an excess of glucocorticoids induces osteoporosis, but the mechanism(s) and the time course of the reduction of bone mass remain uncertain. In order to clarify this issue we carried out a longitudinal clinical and histomorphometric study of patients requiring long-term glucocorticoid treatment. In 23 patients (9 men, 10 post- and 4 premenopausal women) biochemical and bone histomorphometric investigations were carried out before and during treatment with 10-25 mg/day of prednisone. Histomorphometric analysis of bone biopsies of the iliac crest showed that the decrease of TBV (up to -27%, P less than 0.001) occurs predominantly within the first 5-7 months of treatment; during the subsequent stages, which include observations after 12 months of treatment, only minor changes were observed. Therefore trabecular bone loss can be satisfactorily described by a negative exponential function. None of the other histomorphometric parameters (osteoid surfaces, resorption surfaces, etc.) showed significant changes. However, the histological features of the bone biopsies during steroid therapy, showing a virtual lack of osteoblastic activity, ruled out an increase of bone resorption. Moreover, the dynamic study of the bone formation by double tetracycline labelling showed, in a small subgroup of patients, a decrease of the apposition rates (from 0.763 +/- 0.053 to 0.305 +/- 0.074 microns/day (mean +/- SE) after treatment). No significant changes, at any time during steroid treatment, were observed in serum alkaline phosphatase, 25 hydroxyvitamin D, 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone or urinary calcium excretion. Serum calcium increased significantly within the first 1-2 months of therapy and then it returned to baseline. Urinary hydroxyproline excretion decreased significantly within the first 1-2 months and continued to fall throughout the treatment. Thus, both biochemical and histological findings suggest that long-term glucocorticoid therapy causes a reduction of bone turnover, that the bone loss occurs predominantly within the first 6 months of treatment and that patients with lower bone mass have a lower rate of bone loss. PMID- 2306554 TI - Previous pet ownership and Paget's disease. AB - The relationship between pet ownership and Paget's disease (PD) of bone was investigated in 112 patients with PD who were matched with a similar number of community-based controls. There was a significantly increased frequency of dog ownership by patients with PD aged less than 60 years. Multivariate logistic regression analysis revealed that there was a significant age-related increase in risk of PD associated with past or present ownership of either dogs or cats, with younger patients having the greatest risk. These results suggest that slow virus infection of osteoclasts by paramyxoviruses acquired from pets may contribute to the development of Paget's disease in the younger patient. PMID- 2306555 TI - Calcium oxalate crystal formation in patients with hyperparathyroidism and hyperthyroidism and related metabolic disturbances. AB - The crystallization of calcium oxalate in the urine of patients with hyperparathyroidism and hyperthyroidism was studied using a mixed suspension mixed product removal (MSMPR) system. In addition, calcium metabolism in hyperthyroidism and its relationship to urolithiasis was investigated. The urines from all the three groups (normal subjects, hyperparathyroid and hyperthyroid patients) showed reduced nucleation rates and increased growth rates in comparison with the control synthetic urine. The nucleation rate was not significantly different between the three human urine groups, while the growth rate was significantly higher in the hyperparathyroid group compared to the normal and hyperthyroid groups. Crystal volume (suspension density) in the hyperparathyroid group was approximately twice that in the other two groups. Serum and ionized calcium levels in hyperparathyroid patients were higher than in normal subjects, while hyperthyroid patients had levels only slightly higher than those in normal subjects. The hyperparathyroid and hyperthyroid groups differed significantly from the normal group in urinary calcium excretion. These two groups also showed significantly higher levels of serum alkaline phosphatase and urinary hydroxyproline than did the normal group. Although hyperthyroid patients have a calcium metabolism similar to hyperparathyroid patients, the incidence of urolithiasis is no different between hyperthyroid and normal subjects. The results of both crystallization and calcium metabolism in hyperparathyroid patients were not significantly different between those with and without urolithiasis. The result of crystallization was also not significantly different between hyperparathyroid patients with and without hypercalciuria. This study suggests that hypercalciuria alone does not produce urinary stones and that urine from hyperparathyroid patients may contain promotors of calcium oxalate crystallization and calcium stone formation. PMID- 2306556 TI - Bone disease in children with homozygous beta-thalassemia. AB - The histological features of thalassemic bone are imperfectly known, and the roles of bone marrow hyperactivity, iron overload or vitamin D deficiency in the pathogenesis of the disease are not clearly identified. In this study we examined iliac crest biopsies from 17 transfusion-dependent children with homozygous beta thalassemia and severe radiological skeletal thalassemic changes, including widening of medullary spaces and osteoporosis. Rachitic lesions were not observed. Serum ferritin concentrations were increased in all but one subject. Iron deposits were histochemically detected in bone marrow, at the marrow-bone interface, along cement lines and mineralizing perimeters. Minor changes were present in trabecular bone, and osteomalacia was absent. By contrast, cortical bone exhibited severe changes including fissures and focal mineralization defects. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations measured during the winter (December-May, 6.5 +/- 4.9 ng/ml, mean +/- SD, n = 6) and during the summer (June-November, 13.8 +/- 8.4 ng/ml, n = 9) did not differ from those of age-matched children living in the same country. Seven patients had moderate hypocalcemia but no biological signs suggestive of vitamin D deficiency: all had normal alkaline phosphatase activity, normal or slightly elevated plasma phosphate, only two had low plasma 25(OH)D concentrations and two others supranormal values of plasma immunoreactive parathyroid hormone. These results show that iron overload and vitamin D deficiency do not seem to play an important role in the pathogenesis of thalassemic bone disease, which is characterized by cortical lesions probably related to marrow hyperactivity. PMID- 2306557 TI - Decreased serum osteocalcin levels in patients with liver cirrhosis. AB - Serum levels of osteocalcin (OC) have been found to be a specific biochemical parameter of bone formation. We measured serum levels of osteocalcin, parathyroid hormone (PTH) and 25-hydroxyvitamin D (25(OH)D) in 49 patients with liver cirrhosis, who are known to have an increased prevalence of metabolic bone disease, and a matched control group (n = 35). Serum levels of OC were significantly decreased in the patients with liver cirrhosis when compared to control subjects (P less than 0.001). Serum levels of 25(OH)D were decreased (P less than 0.001), whereas no statistical difference was found between the serum levels of PTH in the patients with liver cirrhosis and those of the controls. In a subgroup of 23 patients with cirrhosis of the liver and 34 control subjects, the bone mineral content (BMC) of the non-dominant forearm was determined by single photon absorptiometry. BMC was significantly lower in the patient with liver cirrhosis than the control subjects (P less than 0.04). Our data demonstrate vitamin D deficiency, decreased bone formation and a decreased BMC in patients with liver cirrhosis. PMID- 2306559 TI - Effects of acidic fibroblast growth factor and epidermal growth factor on subconfluent fetal rat calvaria cell cultures: DNA synthesis and alkaline phosphatase activity. AB - The effects of acidic fibroblast growth factor (aFGF) and epidermal growth factor (EGF) were examined in subconfluent fetal rat calvaria cell cultures, in the presence of 2% serum. Maximal effect of aFGF and EGF on DNA synthesis measured by [3H]thymidine incorporation was observed after 18 h. aFGF stimulated DNA synthesis by 3.5-fold with an ED50 of 0.75 ng/ml while a 2.3-fold EGF stimulation was recorded with an ED50 of 0.067 ng/ml. 5-Bromo-2-deoxyuridine staining showed a higher stimulation of proliferation in the scattered cells than in the cell clusters. An 18 h aFGF or EGF treatment decreased alkaline phosphatase (ALP) activity by 40 and 23%, respectively, as compared with control cultures. This inhibition was more pronounced after 48 h in the presence of the effectors but no modification of the ALP electrophoretic mobility was observed. These data suggest that aFGF is a less potent mitogen than EGF and a higher inhibitor of ALP activity in fetal rat calvaria cell culture. PMID- 2306558 TI - Bone surface structure in osteopetrotic grey lethal (gl/gl) and microphthalmic (mi/mi) mutant mice as revealed by scanning electron microscopy. AB - The surface structure of bone from two genetically distinct osteopetrotic strains of mice, grey lethal (gl) and microphthalmic (mi) has been examined by scanning electron microscopy. Although both conditions produce a classical osteopetrotic phenotype the means by which this is achieved is quite different. gl mice appear to retain woven bone and show no evidence of resorption: mi mice show evidence of imperfect remodelling. These results are in accordance with what is already known of osteoclast structure and function in these mutations. PMID- 2306560 TI - Variation of resorption rates in vivo of various bones in immature rats. AB - The 3H-tetracycline method of measuring bone resorption in vivo was applied to the comparison of various whole bones in rats of two different ages. The rat was chosen because it grows via modelling processes and contains little, if any, cortical remodelling except for a small amount of trabecular remodelling. It was found that resorption rates in vivo are high and similar in almost all of the 18 bones measured between birth and 2 weeks of age. However, in weanling rats studied at 4-6 weeks of age, resorption rates in the skull and in the long bones had decreased significantly while remaining high in the vertebrae, scapula, sternum and pelvis. Bones of neonatal rats were quite alike in their rates of bone resorption, but the bones of the weanlings manifested significant heterogeneity in their rates. It is known that anatomic heterogeneity of metabolic turnover of various bones characterizes the mature state in humans and dogs as well. The present data are unique in that they reflect absolute resorption rates in vivo uncomplicated by the extensive re-utilization of calcium inherent in other isotopic or non-isotopic protocols. PMID- 2306561 TI - The use of video in anesthesia record keeping. AB - Although formal comparisons of record keeping systems are difficult, the authors are persuaded that a video system provides substantial advantages over AARK in several (though not all) of its aims and at a substantially reduced cost. The video system might be viewed as a parallel rather than a replacement system in some cases. The authors have been struck by certain capabilities such a video system offers. Not the least of these is the advantage of having a multiple OR monitoring system for use by the floor supervisor to check all rooms easily. The implications of a video technology in clinical research also are important. At present, a clinical trial involving 40 cases is being organized and will require that physiologic parameters be recorded in detail. Plans to use the ubiquitous multichannel strip recorder for logging the parameters have been changed. Video will be used instead, since it is more than adequate to meet most research needs of the department and greatly simplifies the recording of such data at reduced cost. PMID- 2306562 TI - Personality characteristics of biomedical equipment technicians. PMID- 2306563 TI - Design of a microprocessor-based sphygmomanometer. AB - This paper describes the implementation on a microprocessor of a new method for the indirect measurement and recording of the systolic and diastolic blood pressure in humans. The technique is based on a statistical analysis of the cardiac pulse pressure signal. Polynomial relations are derived between the amplitude of the pulsatile pressure waveforms at the systolic and diastolic points and the amplitude of pulse signals detected when the artery is fully occluded. With the dual objective of automating the measurement procedure and minimizing errors, an electronic analog-digital sphygmomanometer that contains suitable electronic instrumentation was developed. The functions of processing the pressure signal, automating the measurement, and recording the results are performed and controlled by a microprocessor. A laboratory prototype embodying this approach was constructed and its performance and reliability were verified using a series of clinical tests. The test results indicate that the device is accurate within acceptable bounds for automated blood pressure instruments. PMID- 2306564 TI - The precision and accuracy of a portable heart rate monitor. AB - A device that would comfortably and accurately measure exercise heart rate during field performance could be valuable for athletes, fitness participants, and investigators in the field of exercise physiology. Such a device, a portable telemeterized microprocessor, was compared with direct EKG measurements in a laboratory setting under several conditions to assess its accuracy. Twenty-four subjects were studied at rest and during light-, moderate-, high-, and maximal intensity endurance activities (walking, running, aerobic dancing, and Nordic Track simulated cross-country skiing. Differences between values obtained by the two measuring devices were not statistically significant, with correlation coefficient (r) values ranging from 0.998 to 0.999. The two methods proved equally reliable for measuring heart rate in a host of varied aerobic activities at varying intensities. PMID- 2306565 TI - Biomedical standards: what do they offer clinical engineering? PMID- 2306566 TI - Intracranial pressure monitoring. PMID- 2306567 TI - A case-control study of congenital heart block: association with maternal antibodies to Ro(SS-A) and La(SS-B). AB - A case control study of congenital complete heart block (CHB) was undertaken to determine the degree of association of this condition with maternal connective tissue disease and with maternal autoantibodies, in particular those to Ro(SS-A). Mothers of cases (n = 18) and controls (n = 72) completed a self-administered questionnaire and donated 10 ml of blood. The odds of giving birth to a child with CHB were increased by a factor of 22 for women with antibodies to Ro(SS-A) and/or La(SS-B) compared with women who did not have these antibodies. Thus the association between CHB and both anti-Ro(SS-A) and anti-La(SS-B) antibodies has been demonstrated in an Australian population and indicates that anti-La(SS-B), as well as anti-Ro(SS-A) antibodies may be a risk factor for the development of CHB. PMID- 2306568 TI - Plasma lactoferrin and neutrophil elastase in rheumatoid arthritis and systemic lupus erythematosus. AB - In order to assess lactoferrin (LF), stored in specific granules of neutrophils, as a marker of inflammation, LF was measured in plasma and serum samples of patients with active rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In active RA, the median plasma LF level (800 ng/ml) was significantly higher than in normal individuals (220 ng/ml) (P less than 0.00001) and patients with active SLE (235 ng/ml) (P less than 0.00001). Median plasma elastase proteinase inhibitor complex (EPIC) and C-reactive protein (CRP) levels were also significantly higher in patients with RA than in normal individuals (P less than 0.00001) and active SLE (P less than 0.00001 for both EPIC and CRP). Elevations of LF, EPIC and CRP in RA were independent of rheumatoid factor titres. Plasma lactoferrin in RA correlated significantly with EPIC (Rs = 0.7, P less than 0.0001), CRP (Rx = 0.72, P less than 0.0001) and absolute neutrophil counts (Rs = 0.483, P less than 0.02), but surprisingly not with the Ritchie index, with which CRP showed a weak but significant correlation (Rs = 0.27, P less than 0.05 greater than 0.025). Thus plasma LF and EPIC are markers of inflammation in RA and their levels may reflect release of mediators of inflammation into the joint space and periarticular tissue. PMID- 2306569 TI - Is there a place for splenectomy in the treatment of Felty's syndrome? PMID- 2306570 TI - Exploring the synovium in 1990. PMID- 2306571 TI - Prosthesis-associated pseudomembrane-induced bone resorption. AB - A pseudomembranous structure invariably develops at the cement-bone interface of implanted prostheses in association with aseptic loosening. The tissue has histological characteristics of a foreign body reaction presumably initiated by repetitive microtrauma-associated release of methacrylate cement and polyethylene wear debris. Explant cultures of pseudomembrane and synovial tissue derived from osteoarthritic patients undergoing revision for cemented hip implant failure have been shown to produce interleukin-1, tumour necrosis factor and prostaglandin E2, recognized mediators of bone resorption. Further, the conditioned media obtained from pseudomembrane cultures could directly effect bone resorption by inducing 45Ca release from prelabelled limb bone rudiments. Results implicate the prosthesis-associated pseudomembrane in the pathogenesis of the bone resorptive process responsible for prosthesis failure. PMID- 2306572 TI - Clinical conundrum. AB - Recent publicity about osteoporosis has stimulated an enormous number of enquiries about treatment and prompted a surge of referrals to rheumatologists. In what circumstances should osteoporosis be considered a disease, how is it best monitored, what treatment would you advocate and for how long? PMID- 2306573 TI - Immunoreactive circulating alpha-interferon is low in Sjogren's syndrome. AB - Circulating alpha-interferon in plasma of 26 patients with Sjogren's syndrome was 0.069 +/- 0.034 ng/ml, a significant decrease compared with 0.119 +/- 0.051 ng/ml for age- and sex-matched healthy subjects (P less than 0.01) and compared with values previously found for healthy donors at ages 1-89 years. The results indicate the inability of Sjogren's syndrome patients to maintain circulating alpha-interferon. PMID- 2306574 TI - New referrals to rheumatology clinics--why do they keep coming back? AB - Many rheumatologists are concerned at the number of return visits being made to their out-patient clinics. This study investigates the outcome of 179 general practitioner referrals to two rheumatology clinics during 1987. Forty-one (34%) of the rheumatoid arthritis patients and six (10%) of the osteoarthritis patients made four or more visits. Junior staff discharged far fewer (11-18%) of patients than did consultants (34%). Multiple linear and multiple logistic regression analyses were performed for the demographic and clinical variables which seemed (on univariate analyses) to predict continuing attendance. The maximum disease severity, diagnosis of rheumatoid arthritis, male sex, patient's perceived reason for referral and the hospital clinic only explained 21% of the variation in the number of visits made. Most of the factors influencing hospital clinic doctors are not easily apparent. The data suggested only one method of reducing unnecessary out-patient attendances, namely to increase the number of patients seen by a consultant. Differences in 'clinic policies' and individual doctor's decision-making strategies will require further study. PMID- 2306575 TI - Factor VIII related antigen in connective tissue disease patients and relatives. AB - This study assayed serum levels of FVIII Rag as a marker of endothelial injury in patients not only with frank connective tissue disease but also in those presenting with Raynaud's phenomenon and in families of those with systemic sclerosis. Elevated levels of FVIII Rag were found in 62% of patients with systemic sclerosis (SS), 38% with systemic lupus erythematosus (SLE), 67% with mixed connective tissue disease (MCTD) and in 17% with primary Raynaud's phenomenon. Twenty per cent of first degree relatives of patients with SS also demonstrated high levels of FVIII Rag and certain antibodies, namely those reacting with U1RNP and the centromere. The association between elevated FVIII Rag and antibodies linked to Raynaud's and vasculitis lends support to antibody involvement in pathogenesis. High levels of FVIII Rag in family members may reflect an increased susceptibility of endothelium to injury particularly since relatives also have a higher frequency of clinical features such as Raynaud's phenomenon. PMID- 2306576 TI - When a patient with known lupus nephritis has persistent proteinuria despite corticosteroids and immunosuppressive treatment can it be assumed that there is continuing disease activity or may it reflect irreparable glomerular damage? How can one be sure? PMID- 2306577 TI - Chronic tuberculous rheumatism (Poncet's disease) in a gymnast. AB - Chronic arthritis, whether primary or reactive, is an unusual manifestation of long standing tuberculosis. We described the case of a 16-year-old gymnast with tuberculous rheumatism (Poncet's disease) secondary to Pott's disease of the dorsal spine. The possible pathogenetic mechanisms are discussed. PMID- 2306578 TI - Diffuse idiopathic skeletal hyperostosis (DISH) of the spine: a risk factor after hip joint replacement? PMID- 2306579 TI - The Lambert-Eaton myasthenic syndrome in association with rheumatoid arthritis. PMID- 2306580 TI - Synovial fluid and serum osteocalcin in arthritis. PMID- 2306581 TI - Hypermobility, arthritis and congenital hip dislocation. PMID- 2306582 TI - Abstracts supplement. British Society for Rheumatology, spring meeting. Newcastle, 28-30 March 1990. PMID- 2306583 TI - Testing a policy for skull radiography (and admission) following mild head injury. AB - There has been, and continues to be, conflicting advice regarding skull radiography following an apparently uncomplicated head injury. Policies on admission are often ill defined. In 1983, representatives of the Royal College of Radiologists met neurosurgeons at a seminar in Harrogate organized by the DHSS and laid down clear, but little publicized, joint recommendations: "The Harrogate Criteria". The survey described here evaluated an existing liberal policy for skull radiography (and a loose policy for admissions) against these recommendations, and it was concluded that the number of patients having skull radiography (74% of head injury attenders) was excessive. Measured against the "Harrogate Criteria", requests for 36% of the adult and 47% of children's skull radiographs did not fulfil these criteria. As a corollary, it was also concluded that loose admissions policies could usefully be altered to comply more closely with the Harrogate recommendations. This would not necessarily reduce the numbers admitted, but would provide casualty officers with a framework on which to base this crucial aspect of clinical decision making, where presently there is often very little structure at all. The authors suggest that all the options have not been fully explored, and that a simple but important alteration to the Harrogate guidelines would provide an even closer link between policy on skull radiography and patient admission. Specifically, most patients who are to be admitted do not need skull radiographs. PMID- 2306584 TI - Asymmetrical pulmonary changes in premature infants with surgical closure of a persistent ductus arteriosus. AB - The chest radiographs of 57 premature infants admitted consecutively with hyaline membrane disease and receiving respirator therapy were reviewed, comparing right and left pulmonary abnormalities. Fifteen infants (Group I) did not develop a persistent ductus arteriosus (PDA). Forty-two infants developed a PDA, which was successfully treated with indomethacin in 17 infants (Group II), while in 25 infants (Group III) the ductus was closed surgically. Analysis of the three groups showed that infants who had undergone surgical closure of their PDA developed significantly more asymmetrical broncho-pulmonary damage. Statistically significant fewer radiological findings of broncho-pulmonary damage were found on the left side in comparison with the right side in the group treated surgically. PMID- 2306585 TI - Calcification of the intrathoracic trachea demonstrated by computed tomography. AB - The presence of intrathoracic tracheal calcification was assessed on computed tomographic (CT) scans of 90 consecutive male and female patients. The presence of calcification was demonstrated to be common and to increase with age. No female preponderance was shown. PMID- 2306586 TI - Assessment and comparison of chest radiography techniques in the United States and Sweden. AB - The United States Center for Devices and Radiological Health and the Swedish National Institute of Radiation Protection started a collaborative project in 1983. The purpose of the project was to test the adequacy and practicability of the United States (US) Nationwide Evaluation of X-ray Trends (NEXT) programme in Sweden. The NEXT protocol for the postero-anterior chest projection was modified and expanded to make it both "statistical" and "investigational" (in the US, NEXT gives mainly "statistical" information). All chest X-ray units in Sweden were surveyed in 1986-87. The project showed that the NEXT programme is applicable to countries other than the United States and provides a standardized protocol that enables intercomparison of the radiological techniques. This paper presents the comparison of the radiological techniques used in Sweden and the United States. The results of the investigational modifications made to the protocol used in Sweden are discussed. Recommendations concerning expansion of the NEXT protocol to include these valuable tools for investigational surveys are presented. PMID- 2306588 TI - Prognostic factors of nasopharyngeal carcinoma: a review of 759 patients. AB - The records of 759 Stage I to IV nasopharyngeal carcinoma patients seen between January 1976 and December 1983 were reviewed. There were 72 (9.5%), 162 (21.3%), 317 (41.8%) and 208 (27.4%) patients with Stage I, II, III and IV disease, respectively. Ho's stage classification was found to give a reliable prognosis. The actuarial survival at 5 and 10 years for Stage I, II, III and IV disease was 80.8%, 71.5%, 40.7%, 17.7% and 33.4%, 48.4%, 30.0%, 9.5%, respectively. The significant factors affecting survival were found using Cox multivariate analysis, N and T stages, the size and degree of fixation of neck nodes, sex, age, the presence of cranial nerve palsy and ear symptoms at presentation. Bilateral neck node involvement, histology subtypes of tumour, headache and nasal symptoms at presentation, the difference in radiation dose to the primary tumour and the neck, the initial haemoglobin and white blood count were not significant factors in the present study. The N stage was found to be prognostically significant even among patient groups stratified for the size and degree of fixation of the neck nodes involved. Women had a better survival rate than men, and the survival of patients less than 40 years old was better than those who were older at 5 years, although by 10 years the survival for the two groups was comparable. PMID- 2306587 TI - The response of the pig lung to fractionated doses of X rays. AB - A radionuclide 133Xe clearance technique has been used to assess changes in the regional gas exchange capacity of the lung after the irradiation of part of the lung of pigs with fractionated doses 250 kV X rays. Changes in the gas-exchange capacity of an irradiated volume of lung were compared with a similar volume of unirradiated lung in each animal. The results from the lung function tests were converted into quantal data on the basis of the percentage of lung function tests in animals showing a greater than or equal to 15% impairment of function in the irradiated lung compared with contralateral unirradiated lung in the same animal. From those quantal data, ED50 values (+/- SE) were obtained for each fractionation schedule. These ED50 values were used to determine time-dose fractionation relationships for both early and late radiation-induced damage to the lung. There was apparently no recovery phase between the early and late phases of damage to the lung. In general, ED50 values for the late effect were slightly lower than those for the early effect, but this only proved significant when measurements obtained at 4 weeks after treatment were included. Varying the period for the assessment of early and late damage did not have a major effect on the results but did suggest that late damage was established in pigs by 39 weeks after irradiation. The linear-quadratic model did not provide a satisfactory fit to the fractionation results for pig lung. However, a modified nominal standard dose equation did provide a better description of the findings. A value of 0.44 +/- 0.06 was obtained for N exponent in the equation for both early and late lung damage when the single-dose data points were included in the analysis. The value of the N exponent was increased to 0.52 +/- 0.08 when the single-dose data were excluded. This increase was not significant. PMID- 2306589 TI - Low-field cine magnetic resonance imaging. PMID- 2306590 TI - Aneurysms involving the intrapetrous internal carotid artery: a rare cause of Horner's syndrome. PMID- 2306591 TI - The radiology of Coffin-Lowry syndrome. PMID- 2306592 TI - Embolization hazard of laser hot-tip catheters and coated guidewires. PMID- 2306593 TI - A pain in the rear. PMID- 2306594 TI - Fractionation sensitivity and the oxygen effect. PMID- 2306595 TI - Chemical protectors: their potential application against occupational radiation hazards. PMID- 2306596 TI - Atlanto-axial rotary fixation. PMID- 2306597 TI - Isoeffective doses. PMID- 2306598 TI - Effect of prolonged exposure to exogenous melatonin on the onset and end of the breeding season and on the growth rate of ewe lambs. AB - The effect of prolonged exposure to exogenous melatonin on the reproductive status and growth rate of ewe lambs was investigated. Ewe lambs (born late March) were given intravaginal melatonin implants on 4 July (group J, n = 10) during anoestrus, or 20 December (group D, n = 10) during the breeding season. A third group (group C, n = 7) received empty implants on 4 July. Plasma progesterone concentrations were used to assess reproductive status. In the control group cyclic ovarian activity began on November 15 +/- 4 days, and ceased on January 28 +/- 8 days. In group J the onset of the breeding season was advanced by 4.9 weeks (occurring on October 12 +/- 4 days; P less than 0.001). The onset of anoestrus was also advanced in this group with 9 out of 10 of the ewes ceasing ovarian activity at least 3.4 weeks in advance of the control ewes (P less than 0.01). In contrast the timing of anoestrus was unchanged in group D, occurring on February 14 +/- 6 days. Melatonin treatment of ewe lambs from early July had no effect on growth rate, whereas treatment from mid-December had a depressive effect. Ewes therefore become refractory to the inductive effects of exogenous melatonin after long-term exposure. The results are consistent with the view that photorefractoriness is due to changes in the processing rather than the generation of the melatonin signal. PMID- 2306599 TI - Sequential changes in plasma progesterone, total oestrogens and corticosteroids in the cow throughout pregnancy and around parturition. AB - Blood samples were taken thrice weekly for 2 weeks from 33 pregnant cows in nine groups, 1 month apart, and twice daily for 8 days commencing 1 week before parturition from eight cows. Plasma progesterone and total oestrogens were quantified by validated radioimmunoassays and total corticosteroids by a competitive protein binding technique. During the first 3 months of pregnancy, no remarkable changes were observed for the three hormones studied. From the fourth month on, concentrations of progesterone and total corticosteroids decreased significantly (P less than 0.05) and remained fairly constant until the ninth month. Values of total oestrogens increased significantly (P less than 0.05) from the fourth to the sixth month and thereafter remained unchanged. In the periparturient cows, progesterone levels decreased linearly (P less than 0.01) during the 3 days preceding delivery. Concentrations of total oestrogens rose sharply from day -5 and peaked at calving. Values of total corticosteroids increased dramatically on the sixth day and also at 24 hours before parturition. These results suggest that, contrary to earlier studies, plasma corticosteroids could have a primary key role for triggering parturition in cows. PMID- 2306600 TI - A combined deficiency of factor VIII and contact activation defect in a family of cats. AB - The coagulation parameters of a litter of kittens born to an obligate carrier of haemophilia A (classical haemophilia, factor VIII deficiency) are described. Three of four kittens were found to have an intrinsic coagulation defect, but only one was haemophilic. Factor XII deficiency was confirmed in one female, the other female and the dam being carriers of the defect. A confirmed haemophilic male from a previous litter was also found to be a factor XII deficient carrier. PMID- 2306601 TI - Plasma concentrations of cortisol, testosterone, glucose and blood gases in male goats during anaesthesia with pentobarbitone sodium. AB - Fasting for 24 h had no statistically significant effect on cortisol, glucose or testosterone concentrations. A dose of pentobarbitone sodium which induced light anaesthesia resulted in an immediate decrease in cortisol values from 5.0-11.1 ng/ml to 2.2-3.6 ng/ml until waking-this latter event was accompanied by an excessive release of cortisol (up to 16.6 ng/ml). In two out of three goats testosterone concentrations decreased from 4.0-9.0 ng/ml to less than 0.5 ng/ml after pentobarbitone; low values were maintained for 4.5-6 hours. Glucose concentrations were unaffected. Precise doses of pentobarbitone (20 mg/kg or 30 mg/kg) resulted in similar cortisol profiles as above but with higher concentrations achieved upon waking from the higher dose of pentobarbitone. On two out of nine occasions increased PCO2 values were recorded concurrently with increased cortisol concentrations during the period of anaesthesia, suggesting that a sufficiently strong stressful stimulus can break through the pentobarbitone blockade. PMID- 2306602 TI - The effect of experimentally induced subclinical mastitis on milk yield of ewes and on the growth of lambs. AB - In each of two experiments, subclinical mastitis was induced by inoculating both mammary glands of Welsh-Mountain and Dorset-Horn ewes with a coagulase-negative staphylococcus; groups of control ewes were also included. After inoculation, the somatic cell counts of milk of the inoculated ewes increased (P less than 0.01) and the milk yield decreased (P less than 0.01). The lambs of the inoculated ewes had a poorer growth than lambs of the control ewes (P less than 0.01). PMID- 2306603 TI - Antimicrobial susceptibilities of Staphylococcus aureus isolated from animal and human sources in Brazil. AB - The susceptibilities of 760 Staphylococcus aureus strains isolated from animal infections (400), human infections (300) and healthy human carriers (60) to seven antibiotics were determined by an agar dilution technique. The isolates from human infections were more resistant to a wider spectrum of antibiotics than were the strains from animal infections and healthy human carriers. Amikacin and gentamicin were the most active drugs against all groups of strains. PMID- 2306604 TI - Experimental Haemophilus somnus infection in pregnant cattle. AB - Of five pregnant cows inoculated intravenously with 5 X 10(8) viable 'Haemophilus somnus', one aborted within 5 days and excreted 'H. somnus' from the vagina for a further 7 weeks. A second cow proceeded to full term parturition but both it and its apparently healthy calf persistently excreted 'H. somnus'. The other animals underwent normal full term calvings and 'H. somnus' was not isolated from them or their calves. Lesions attributable to 'H. somnus' were detected only in the aborted fetus which showed an acute generalized inflammatory cell response consistent with a systemic Gram-negative bacterial infection. 'H. somnus' was isolated from all fetal tissues, including the placenta. The fetus and placenta also showed evidence of damage prior to inoculation. The placental damage may have predisposed the fetus and placenta to infection with 'H. somnus'. The placental epithelial cells contained intracytoplasmic organisms with the morphological and antigenic properties of 'H. somnus'. PMID- 2306605 TI - Control of Campylobacter fetus in artificially contaminated bovine semen by incubation with antibiotics before freezing. AB - Fresh, diluted semen containing 1.55 X 10(6) cfu/ml of Campylobacter fetus subsp. venerealis was incubated with 500 iu of penicillin, 500 micrograms of streptomycin, 160 micrograms of lincomycin and 300 micrograms of spectinomycin per ml at 35 degrees C for 0, 1, 2, 5, 10, 20 or 40 minutes. The semen was cooled to 5 degrees C, packaged in 0.25 ml French straws and then frozen in liquid nitrogen for 2 weeks. Immediately after thawing and removal of the antibiotics by centrifugation semen samples from each of the seven treatment groups were cultured as for C. fetus. Semen samples were also examined by in-vitro tests for sperm motility prior to and post-freezing. Incubation with the antibiotics for 5, 10, 20 or 40 min prior to freezing reduced the numbers of C. fetus in the semen to non-detectable levels in 38%, 69%, 88% and 100% of samples respectively. The incubated semen showed no significant reduction of sperm motility although fertility trials have not been done. PMID- 2306606 TI - Feeding antibiotic-contaminated waste milk to calves--effects on physical performance and antibiotic sensitivity of gut flora. AB - The effect of feeding calves antibiotic-containing waste milk was studied in two trials. In the first trial both fermented and unfermented waste milk were fed and in the second trial only unfermented milk was used. The antibiotic-containing milk had a poor palatability and rejection rates were high. Growth rates of the calves were poor and in the second trial differed significantly from those of the control calves which had received milk substitute. Faecal E. coli were monitored for antibiotic resistance. In the first trial, the geometric mean minimal inhibitory concentration for streptomycin was significantly higher for isolations from calves fed antibiotic-containing milk, but no differences were observed for ampicillin. In the second trial, the percentage of resistant E. coli and enterococci was determined but no differences were observed between isolations from calves fed antibiotic-containing milk and the controls. The ambient conditions in the United Kingdom did not encourage the rapid natural fermentation, which would degrade the antibiotics and make it an acceptable food, and it was concluded that the high numbers of bacteria in the product may present disease risk. PMID- 2306607 TI - Cerebrospinal fluid studies in normal cows and cases of bovine spongiform encephalopathy. PMID- 2306608 TI - Thymic lymphosarcoma with metastases causing spinal cord compression and pelvic limb paresis in a heifer. AB - Neurological examination of a heifer displaying pelvic limb ataxia and paresis progressing to a dog-sit position but with normal thoracic limb function indicated a spinal cord lesion in the low thoracic/high lumbar region. The progressive neurological deterioration despite normal radiological and cerebrospinal fluid findings were suggestive of a non-inflammatory, non-traumatic extradural compressive lesion; this was subsequently shown to be a lymphosarcoma. PMID- 2306609 TI - Small ruminant trypanosomiasis in Guyana--a preliminary report. AB - Trypanosomes identified as Trypanosoma vivax were found infecting nine sheep (4.6%) and one goat (1.3%) on four of 11 farms surveyed on coastal Guyana. Animals sampled on another farm situated in the Rupununi savannahs gave negative results. Haematological techniques preferred for studies of this nature were the haematocrit centrifuge technique (HCT) and the thick blood smear technique. PMID- 2306610 TI - A neurotransmitter specific functional recovery mediated by fetal implants in the lesioned spinal cord of the rat. AB - In the electrophysiologic test of the hindlimb withdrawal reflex where the long latency component is found to be dependent on noradrenaline (NA), implants of fetal NA tissue in lesioned animals result in a recovery of NA dependent function proportional to the number of catecholamine fluorescent cells in the implants. PMID- 2306611 TI - Effects of single and simultaneous combined nanoinjections of Met-enkephalin into rat midbrain and medulla on activity of differentially nociresponsive ventral medullary neurons. AB - Neuronal activity classified by receptive field, adequate stimulus, and raphe spinal (R-S) projection in 48 lightly anaesthetized rats was recorded from raphe magnus (RM) area. Effects of nanoinjections of Met-enkephalin in periaqueductal gray (PAG; 2 or 10 micrograms), nucleus reticularis paragigantocellularis (PGC; 1 or 5 micrograms), and both sites (conjointly) were studied. Most of the 78 neurons studied responded to noxious stimulation, some with increased responses ('on-cells') and some with decreased responses ('off-cells'). MAJOR FINDINGS: (1) Met-enkephalin in PAG and PGC depressed the response of on-cells and enhanced the response of off-cells; (2) for a given RM or R-S cell, PAG and PGC effects were typically identical; and (3) conjoint injections tended to produce greater effects than single effects, whether enhancing or depressing. PMID- 2306612 TI - Ganglioside GM1 prevents and reverses toluene-induced increases in membrane fluidity and calcium levels in rat brain synaptosomes. AB - The effects of exposure to ganglioside GM1 and to toluene in vitro upon synaptosomal integrity have been examined using fluorescence polarization of two probes: 1-[4(trimethylamino)phenyl]-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl 1,3,5-hexatriene (DPH) to measure membrane anisotropy, and the fluorescent indicator fura-2 to assay levels of cytosolic calcium [( Ca2+]i). The anisotropy of both TMA-DPH and DPH was decreased by toluene, implying increased membrane fluidity. The decrease in TMA-DPH but not in DPH anisotropy was prevented by pretreatment with GM1 in concentrations as low as 10 microM. This is not an additive interaction since 10 microM of GM1 alone did not significantly modulate TMA-DPH anisotropy. When the GM1 treatment succeeded the addition of toluene the decrease in anisotropy of both probes was reversed. Toluene treatment increased [Ca2+]i in a dose- and time-dependent manner. This increase could partially be both prevented and reversed by treatment with 50 microM of GM1. These effects may reflect an additive interaction, since this concentration of GM1 alone reduced [Ca2+]i. The present results show that toluene increases membrane fluidity and intracellular calcium levels. These effects may be counteracted by the endogenous compound GM1. PMID- 2306613 TI - Involvement of amygdala pathways in the influence of post-training intra-amygdala norepinephrine and peripheral epinephrine on memory storage. AB - These experiments examined the role of two major amygdala afferent-efferent pathways--the stria terminalis (ST) and the ventral amygdalofugal pathway (VAF)- in mediating the effects, on memory storage, of post-training intra-amygdala injections of norepinephrine (NE) and subcutaneous (s.c.) injections of epinephrine (E). Rats with either ST lesions or VAF transections and sham operated rats were trained on a one-trial step-through inhibitory avoidance task and immediately after training received intra-amygdala injections of NE or a buffer solution. Other groups of VAF-transected animals received post-training s.c. injections of E or saline. ST lesions blocked the memory-enhancing effect of intra-amygdala injections of a low dose of NE (0.2 microgram) as well as the amnestic effect of a high dose of NE (5.0 microgram). In contrast, VAF transections did not block the memory-enhancing effect of NE (0.2 microgram). However, VAF transections attenuated the memory-enhancing effect of s.c. injections of E: the effective dose of E was shifted from 0.1 to 0.5 mg/kg. These findings, considered together with previous evidence that ST lesions block the memory-enhancing effect of peripheral E injections, suggest that the VAF is involved in mediating the central influence of peripheral E on amygdala functioning, while the ST is involved in mediating amygdala influences on memory storage elsewhere in the brain. PMID- 2306614 TI - Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit. AB - Perfusates were taken from the superficial layers of the subnucleus caudalis of the trigeminal sensory nuclear complex (SpVc), the first relay station of dental pain, with a push-pull cannula system and were assayed for endogenous serotonin (5-HT) and catecholamines by high-pressure liquid chromatography with an electrochemical detection. Spontaneous release of 5-HT and epinephrine was observed, while that of norepinephrine was not. Tooth pulp stimulation (ST) tended to increase the level of 5-HT in the perfusates. Pretreatment with morphine at a dose of 10 mg/kg (i.v.) significantly enhanced the release of 5-HT. However, there was no significant difference in morphine effect on the 5-HT level between stimulated and non-stimulated animals. Systemic administration of morphine (10 mg/kg i.v.) completely inhibited the release of immunoreactive substance P from the superficial layers of SpVc evoked by ST, and this inhibition was antagonized by local application of methysergide (10(-4) M). These results suggest that in the superficial layers of SpVc, morphine may primarily activate the descending 5-HT pathway which serves to modulate dental pain transmission. PMID- 2306615 TI - Basal forebrain cell loss following fimbria/fornix transection. AB - Following fimbria/fornix transection, cells in the medial septum appear to undergo retrograde degeneration as shown by Nissl and acetylcholine esterase (AChE) staining. Recent studies using immunocytochemical techniques have also demonstrated loss of choline acetyltransferase (ChAT) and nerve growth factor receptor (NGFr) labeling of neurons in this region. Whether the apparent loss of ChAT- and NGFr-positive neurons is the result of the actual death of these neurons, or is instead a loss of ChAT enzyme or NGFr expression below levels detectable by immunocytochemical methods, remains an unresolved issue. In order to address this question, rhodamine-labeled fluorescent latex microspheres were injected into the hippocampus where they retrogradely transported to the cell bodies of the medial septum. Five days later these animals received either unilateral or bilateral fimbria/fornix lesions and were allowed to survive an additional 4 weeks. Compared to unlesioned control animals, unilaterally lesioned animals showed a 91% loss of fluorescently labeled cells and bilaterally lesioned animals showed a 93% loss. The inability to detect the fluorescent microspheres in the medial septum suggests that the majority of medial septal cells die after fimbria/fornix transection. ChAT and NGFr immunohistochemical staining were also performed. Cells stained for ChAT were reduced in number by 92% in animals with unilateral lesions and by 75% in animals with bilateral lesions, while NGFr stained cells were reduced in number by 75% in animals with unilateral lesions and by 68% in animals with bilateral lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306616 TI - Loss of true blue labelling from the medial septum following transection of the fimbria-fornix: evidence for the death of cholinergic and non-cholinergic neurons. AB - Many neurons in the medial septal nucleus lose their transmitter-associated enzyme staining following axotomy in the proximal fimbria-fornix (FF), but it is not clear if these neurons have died or persist in a shrunken and subfunctional state. To investigate this further, septal neurons projecting through the FF were labelled with the fluorescent dye, True blue, by retrograde transport from multiple bilateral injection sites in the hippocampus. True blue-labelled neurons and cholinergic neurons immunohistochemically stained for choline acetyltransferase (ChAT) were then quantitatively compared in neighbouring sections through the medial septum 28 days after complete unilateral transections of the proximal FF. The number of True blue and ChAT positive cells ipsilateral to the FF lesion showed significant (P less than 0.001) declines of 51.4% and 71.1%, respectively, relative to the unlesioned side. Cell loss was considerably more severe among large neurons, such that 78.0% and 92.7% of True blue and ChAT labelled cells larger than the normal mean, but only 40.1% and 68.0% of True blue and ChAT labelled cells smaller than the normal mean size were lost. This indicates either that larger neurons were more prone to cell loss, or that some (but not all) large neurons persisted in a shrunken form. Histograms showed no increase in cell number in any of the smaller size categories and a substantial decrease in most cases, indicating that shrinkage alone could not account for the loss of all large neurons. Since True blue can remain present in brainstem cholinergic neurons surviving for over 365 days after axotomy, loss of True blue suggests breakdown of membrane integrity and cell death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306617 TI - The expression of phosphorylated and non-phosphorylated forms of MAP5 in the amphibian CNS. AB - MAP5 is a microtubule-associated protein that in rat and quail is more abundant in the developing than in the adult brain. Previous studies in our laboratory have shown that MAP5 can be resolved into two forms by SDS-PAGE, MAP5a and MAP5b (Mr 300,000-320,000 Da) with MAP5a representing a highly phosphorylated form of this protein. In the present study, the relationship between MAP5 expression and neuronal growth and plasticity was investigated by assessing the amount and distribution of MAP5a and MAP5b in both the developing Xenopus brain and in different regions of the adult brain where neurons of varying growth potential and plasticity are present. In the larval and metamorphic Xenopus brain, like the neonatal rat brain, MAP5 is present in the highly phosphorylated form, MAP5a, and in concentrated in neuronal processes. In the adult Xenopus brain, MAP5a remains high in the optic tectum but, like the situation in the adult rat brain, is undetectable in the telencephalon. Immunohistochemistry showed that MAP5 was concentrated in the outer layer of the tectum, where ingrowing and plastic retinal ganglion cell axons are found. The correlation between MAP5 expression and phosphorylation and growth potential suggests that this molecule plays an important role in the regulation and organization of the neuronal cytoskeleton during neurite outgrowth and plasticity. PMID- 2306618 TI - Low threshold unilateral and bilateral facial movements evoked by motor cortex stimulation in cats. AB - Organizational features of the ipsilateral representation in the cat face motor cortex were investigated by using the technique of intracortical microstimulation (less than 30 microA). In 4 intact animals, 61 efferent zones controlling facial muscles were identified. They were devoted to contralateral muscles (contralateral efferent zones; n = 35), ipsilateral muscles (ipsilateral efferent zones; n = 8) or symmetrical muscles of both sides (bilateral efferent zones; n = 18). Contralateral efferent zones were found within both the rostral part of the coronal gyrus and the lateral bank of the presylvian sulcus, whereas ipsilateral and bilateral efferent zones were exclusively localized to the rostromedial region of the face motor cortex. Movement thresholds proved to be lowest at the contralateral efferent zones and highest at the ipsilateral efferent zones, with intermediate values at the bilateral efferent zones. Latencies of suprathreshold EMG responses evoked from contralateral and ipsilateral efferent zones were the shortest and the longest, respectively; intermediate values were found upon stimulation of sites from bilateral efferent zones. The efferent zones identified in 3 lesioned animals (two cats with contralateral motor cortex ablation and one cat with transection of the rostral two thirds of the corpus callosum) were contralateral (n = 14), bilateral (n = 13), and ipsilateral (n = 9). Mean thresholds of effective sites from bilateral and ipsilateral efferent zones in lesioned preparations were not significantly higher than those in intact animals. This would thus suggest that extracallosal pathways may account for ipsilateral responses. PMID- 2306619 TI - Variability of the influence of a visual task on the active micromechanical properties of the cochlea. AB - The effect of a visual task on the active micromechanical properties of the cochlea studied by the evoked otoacoustic emissions (EOAEs) has been the subject of only one published study (Brain Research, 44 (1988) 380-383). In order to examine the reliability of this effect, a similar study has been run on 16 subjects. A significant decrease in EOAEs during a visual task was obtained for 3 subjects. The two subjects whose decrease was the most significant were tested again one month later and the same effect was found. This striking interindividual variability is discussed in terms of olivo-cochlear neuronal excitability. PMID- 2306620 TI - Collateral branching innervation of rat molar teeth from trigeminal ganglion cells shown by double labelling with fluorescent retrograde tracers. AB - Somatotopic projections of each maxillary molar tooth were defined by injecting individual teeth with True blue and plotting the location of fluorescent cells in sections of the trigeminal ganglia. Collateral branching was investigated by injecting True blue and Diamidino yellow into pairs of maxillary molar teeth and examining the ganglia for double labelled cells. Maxillary molar teeth project to the lateral ophthalmomaxillary region of the ipsilateral ganglion with extensive overlap of the projections from individual teeth. Double labelling with both dyes demonstrated considerable collateral branching from single trigeminal ganglion cells to the molar teeth. PMID- 2306621 TI - The central medial nucleus: thalamic site of seizure regulation. AB - This study demonstrates that the central medial intralaminar nucleus (CeM) controls generalized seizure threshold and expression, and that these functions are under gamma-aminobutyric acid (GABA)ergic control, with significant differences between receptor subtypes. Injections of the GABAA-agonist piperidine 4-sulfonic acid and the GABAB-agonist (-)baclofen in the CeM markedly facilitated myoclonic and clonic seizures, but had different effects on tonic seizures. These results are best explained by the concept that the CeM is not a site of seizure origin or spread but rather regulates other structures involved in seizures. PMID- 2306622 TI - Clonidine impairs recovery of beam-walking after a sensorimotor cortex lesion in the rat. AB - Beam-walking in the rat is a useful model for studying the effects of drugs on motor recovery following brain injury. In the present experiment, the effect of clonidine HCl on beam-walking recovery was investigated. Groups of rats were first trained to traverse a narrow elevated beam and then subjected to a right sensorimotor cortex suction-ablation injury. After 24 h, each rat received a single dose of clonidine HCl (20, 60, or 200 micrograms/kg, i.p., salt weight) or saline. Recovery of beam-walking ability was scored over the next 12 days. Treatment with clonidine significantly slowed the rate of recovery (Kruskal Wallis H = 8.755, df = 3; 0.02 less than P less than 0.05). Furthermore, the impairment persisted for at least 5 days after the rats were treated (Kruskal Wallis H = 8.47, df = 3; 0.02 less than P less than 0.05). These data are consistent with the hypothesis that norepinephrine, working through central alpha 2-adrenergic receptors, influences motor recovery after a unilateral sensorimotor cortex lesion in the rat. Since many stroke patients are treated with centrally acting antihypertensive drugs, the potential effects of specific classes of these drugs during the recovery period, should be carefully considered. PMID- 2306623 TI - Human striatal cholinergic neurons in development, aging and Alzheimer's disease. AB - The cross-sectional area of cholinergic neurons stained immunohistochemically for choline acetyltransferase were measured in the striatum of infants, young adults, aged individuals and patients with Alzheimer's disease. Cholinergic neurons were distributed throughout the caudate nucleus and the putamen and displayed no significant variations in size across the two structures. The cross-sectional area of striatal cholinergic neurons was smaller in infants as compared with all other groups examined. No significant changes were observed in the size of these neurons as a consequence of aging or Alzheimer's disease. PMID- 2306624 TI - Gastrin-17 injected into the hypothalamic paraventricular nucleus can induce gastric acid secretion in rats. AB - Injections of picomolar quantities of gastrin-17 into the hypothalamic paraventricular nucleus increased gastric acid output in anesthetized rats. The response was dose-dependent, and it was blocked by atropin and by vagotomy. The same doses, injected intravenously, intraventriculary or into sites far from the nucleus, did not increase the output. Cholecystokinin-8 injected into the nucleus had no effect on the acid output. PMID- 2306625 TI - Deafferentation in the rat increases mechanical nociceptive threshold in the innervated limbs. AB - In this study in the rat, we evaluated the effect of unilateral, multiple cervical dorsal rhizotomy (C5-T1) on nociceptive thresholds in the unoperated limbs. This was tested by measuring the vocalization threshold to paw pressure. We report that deafferentation by dorsal rhizotomy results in a delayed, but transient increase in mechanical nociceptive thresholds in the 3 innervated limbs. PMID- 2306626 TI - Corticospinal responses to electrical stimulation of motor cortex in the rat. AB - Direct and indirect corticospinal responses to electrical stimulation of motor cortex were identified in urethane-anesthetized rats. 'Killed-end' recordings were taken from the corticospinal tract at the level of the cervical cord (C1-C2) and from the medullary pyramid. The identities of direct (D) and indirect (I) corticospinal responses were confirmed by: (1) removing motor cortex to eliminate I activity, and (2) pharmacologically increasing neocortical excitability, prior to any lesions, to increase I activity. Our data indicate that the conduction velocity of the fastest corticospinal fibers is approximately 18 m/s. Our identification of the components of the corticospinal response will permit the interpretation of the more complicated surface or 'non-killed-end' depth recordings which have shown particular utility in evaluating spinal cord damage. PMID- 2306627 TI - Calbindin D-28K immunoreactivity in the cat's superior olivary complex. AB - The calcium binding protein, calbindin D-28K (CaBP), was identified immunohistochemically in the cat's superior olivary nuclei. Intense somatic labeling was observed in the medial and lateral nucleus of the trapezoid body. The lateral superior olive contained dense, perisomatic, terminal bouton labeling surrounding unlabeled somata, while the medial superior olive exhibited the least amount of labeling, comprised only of a few fiber fragments. PMID- 2306628 TI - Suprachiasmatic nuclei influence hibernation rhythms of golden-mantled ground squirrels. AB - Hibernation and body mass rhythms were studied in 13 golden-mantled ground squirrels maintained in an LD 12:12 photoperiod at 5 degrees C. Complete or partial ablation of the suprachiasmatic nuclei (SCN) disrupted normal hibernation rhythms. Over the course of 2 years, several animals progressed through 4 hibernation cycles, one squirrel manifested two abnormally long hibernation seasons, and another failed to hibernate. Squirrels with intact SCN exhibited normal circannual hibernation rhythms at intervals of 11.5 +/- 0.3 months. Hibernation coincided with the weight loss phase of the body mass cycle in control squirrels, but these two rhythms were dissociated in animals with lesions of the SCN. The annual plasma testosterone rhythm was normal or slightly phase delayed in squirrels with SCN lesions maintained at 23 degrees C. The SCN may be part of a neural circuit that mediates circannual organization of hibernation rhythms. PMID- 2306629 TI - Activation and proliferation of the isolated microglia by colony stimulating factor-1 and possible involvement of protein kinase C. AB - Microglia were isolated from primary mixed brain cell culture of normal newborn mice and then cultivated. They were able to be maintained in vitro for 1-2 months, but incorporated little [3H]thymidine under normal culture conditions. When treated with the conditioned medium of L929 mouse fibroblast cells as a crude CSF-1 (mouse macrophage-colony stimulating factor) or purified CSF-1, microglia showed morphological changes and increased in both cell number and [3H]thymidine uptake. In addition, crude CSF-1 increased lysosomal enzyme activity and superoxide anion formation of microglia up to 2 and 3.8 fold as control value, respectively. These effects of CSF-1 were not observed in the purified astrocyte culture. Purified microglia had CSF-1 receptors which were recognized by the anti-CSF-1 receptor antibody that arose from a peptide of a product of proto-oncogene, c-fms. 12-O-Tetradecanoylphorbol-13-acetate (TPA) also increased microglia cell number and their biochemical activities, suggesting the possible involvement of protein kinase C activation. Protein kinase inhibitors, such as staurosporine or H-7, inhibited the effects of both CSF-1 and TPA. These results indicate that microglia may be regulated in its biochemical and proliferation activities by CSF-1 and that this may occur via activation of protein kinase C. PMID- 2306630 TI - Cortico-thalamo-cortical projection between visual cortices. AB - The present experiments showed that there is a cortico-thalamo-cortical projection system in the cat, which originates from the primary visual cortex, relayed by the lateral part of the lateral posterior nucleus of the thalamus, and reaching the medial bank of the lateral suprasylvian visual area. This finding suggests that the thalamus can play a role in transmission of cortical signals from one cortical area to another. PMID- 2306631 TI - Facilitated ERG recovery in taurine-treated bovine eyes, an ex vivo study. AB - Excorporal bovine eye with stable ERG patterns were used in this study to examine the possible antihypoxic property of the taurine. Taurine (1 mM) given prior to or after the on-set of hypoxia facilitated the retinal recovery as indicated by the B-wave amplitude changes. This observation is consistent with previous observations in hippocampal slice and other tissues which suggests an antihypoxic function of this sulfur-containing amino acid. PMID- 2306632 TI - The role of GABA in detecting visual motion. AB - The basic computations underlying the extraction of motion from the visual environment have been characterized in great detail. A non-linear interaction, such as a multiplication, between neighbouring visual elements was shown to be the core of biological motion detectors in different species ranging from insects to man. GABA (gamma-aminobutyric acid)-ergic inhibitory synapses suppressing the responses to motion in one direction but not in the other are widely accepted to be the cellular basis for this non-linear interaction. Based on model predictions we can show in combined pharmacological and electrophysiological experiments that in the fly motion detection system GABAergic synapses do not play this role but rather are involved in another important step of motion computation. This makes a reconsideration of the role of inhibition in other motion detection systems necessary. PMID- 2306633 TI - A monoclonal antibody 5E5 recognizes an intranuclear antigen selectively present in a subpopulation of the neurons. AB - Monoclonal antibody 5E5 labeled the nuclear antigen of the neurons in the guinea pig and rat central nervous systems including the cerebrum, cerebellum, spinal cord and retina. This antibody could discriminate neurons even among the same cell class. In in vitro study, only 10% of dividing PC12 cells was labeled with this antibody. An electron microscopic immunohistochemical study also revealed that this antibody selectively labeled heterochromatins in the neurons. Although we could not obtain any positive result by an immunoblot study, the antigenicity was remarkably diminished by the DNase I or S1 nuclease treatment on the tissue sections whereas RNase and trypsin was ineffective. These results suggested that this antigen might be a single-stranded DNA-protein complex resistant to proteolytic procedures, and possibly related to cell function or state of differentiation. PMID- 2306634 TI - Cerebellar vermis: essential for classically conditioned bradycardia in the rat. AB - The effects of lesions of the cerebellar vermis on the acquisition of heart-rate conditioning in rats was examined. Lesions of the vermis severely attenuated the acquisition of conditioned bradycardic responses in a simple conditioning procedure in restrained rats. Importantly, the vermal lesions did not affect resting heart-rate, unconditioned heart-rate orienting responses to a tone stimulus or unconditioned heart-rate responses to the shock unconditioned stimulus. It is concluded that the cerebellar vermis is an essential component of a heart-rate conditioned response circuit in the rat. The similarities between these effects and those following manipulations of the amygdala are discussed. PMID- 2306635 TI - Stimulation of the subcallosal fornix excites neurones in the cat preoptic region which project to the medial basal hypothalamus and in the medial forebrain bundle. AB - The projection of neurones in the cat preoptic region driven by stimulation of the subcallosal fornix was systematically explored. We found 19% projected to the medial basal hypothalamus (MBH) and 10% projected in the medial forebrain bundle (MFB). Neurones projecting to the MBH were driven more often by stimulation of the lateral aspect of the fornix than the medial aspect (P = 0.006) and these neurones were thought to lie in the medial division of the preoptic nucleus (MPNm) since they were found significantly more often in the medial 0.6 mm of the preoptic region than more laterally (P = 0.028). A reverse projection from the preoptic region in the fornix is also suggested based on the finding of 24 antidromically activated neurones in the preoptic region following stimulation of the fornix. PMID- 2306636 TI - The effects of electrical stimulation of A and C visceral afferent fibres on the excitability of viscerosomatic neurones in the thoracic spinal cord of the cat. AB - Single unit electrical activity has been recorded from viscerosomatic neurons in the lower thoracic spinal cord of decerebrate spinalized cats. The responses of the cells to electrical stimulation of afferent fibres in the splanchnic (SPLN) nerve and the effects of repetitive stimulation of somatic and visceral afferent C-fibres have been studied. Four groups of viscerosomatic neurones could be distinguished according to the type of visceral afferent input of the cells: (1) A-only cells (32.9%), driven only by stimulation of A delta afferent fibres in the SPLN nerve; (2) C-only cells (3%), driven only by stimulation of C afferent fibres in the SPLN nerve; (3) A + C cells (45.7%), driven by both A delta and C afferent fibres in the SPLN nerve; and (4) A + C? cells (18.6%), driven by A delta visceral afferents and showing signs of responsiveness to C-fibres though lacking a distinct response volley to visceral C-fibre activation. Two cells of the A + C group and located in lamina I of the dorsal horn responded to SPLN nerve stimulation in a manner consistent with the afferent fibre composition of the nerve, that is, showed evidence of strong monosynaptic links with SPLN afferent C-fibres and weaker responses to SPLN A delta afferents. Excitability changes of viscerosomatic neurones ('wind up', 'wind down' and changes in background activity) were also observed in the majority of neurones following electrical stimulation of somatic and of visceral afferent C-fibres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306637 TI - The effect of acetylcholine depletion on behavior following traumatic brain injury. AB - Rats were injected with either saline; A-4 (40 mg/kg, i.p.), a bis tertiary amine derivative of hemicholinium-3; or A-5 (50 micrograms/kg, i.p.), a bis quaternary amine derivative of hemicholinium-3, 1 h prior to moderate fluid percussion brain injury. A variety of reflexes and responses were measured up to 60 min following injury, and body weight and several neurological measures were taken daily up to 10 days following injury. Pretreatment with either A-4 or A-5 significantly attenuated components of transient behavioral suppression, as well as more enduring deficits in body weight and beam walk and beam balance performance. A-4 administered prior to fluid percussion was found to reduce striatal, but not pontine, acetylcholine content. A-5 did not significantly reduce acetylcholine content in either area. Both A-4 and A-5 pretreatment prevented a significant increase in acetylcholine content in the cerebrospinal fluid following fluid percussion injury; however, only A-5 significantly reduced plasma acetylcholine content. These results confirm cholinergic involvement in the production of both transient and longer-lasting behavioral deficits following traumatic brain injury. Furthermore, traumatic brain injury may allow plasma constituents to gain access to the central nervous system. PMID- 2306638 TI - Astroglial ablation prevents MPTP-induced nigrostriatal neuronal death. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent neurotoxin which destroys nigrostriatal dopamine neurons, resulting in irreversible idiopathic parkinsonism. MPTP displays dopaminergic neurotoxicity to humans, monkeys, cats and rodents. The oxidative conversion of MPTP to 1-methyl-4-phenylpyridine (MPP+) is responsible for the generation of its neurotoxicity. This metabolism is mediated by the action of monoamine oxidase B, which in the substantia nigra pars compacta (SNc) is localized specifically in astroglia. Employing various combinations of intra-SNc injections of MPTP and the astroglia-specific toxin, L alpha-aminoadipic acid (L-alpha-AA), we examined the effects of selective astroglial ablation on MPTP-induced nigrostriatal neuronal death in the rat. Varying nigrostriatal cell loss was assessed primarily by the aid of fluorescent retrograde axonal tracing. Treatment with MPTP alone caused tremendous nigrostriatal cell loss, while intra-SNc co-injections of MPTP and L-alpha-AA produced protection against MPTP neurotoxicity in a dose-dependent fashion. Similar effects of L-alpha-AA occurred in the SNc pretreated with the gliotoxin just prior to or 1 day before MPTP administration. However, this preventive action by L-alpha-AA was considerably reduced 3 days after its intra-SNc injection. Interestingly, 7 days following L-alpha-AA pretreatment, nigrostriatal cell loss was even enhanced rather than attenuated by MPTP administered into the SNc. Thus, our data provide clear morphological evidence for the critical importance of the presence of astroglia in the onset of MPTP neurotoxicity. PMID- 2306639 TI - Classification of muscle spindle afferents in the peroneus brevis muscle of the cat. AB - Muscle-spindle afferents are commonly classified according to their conduction velocity. Under certain conditions such classifications may not be feasible and another form of identification is required. In this study 5 tests, comprising either quantitative or qualitative criteria, have been evaluated as a means of classifying spindle afferents. The choice of these tests was made on the basis of predicted physiological differences arising from the structural variations in the endings. Prior conditioning of the spindles was found to enhance the distinction between the two types of afferent. All the tests generated similar identifications with a maximum of 10% of afferents being classified differently by any two tests. PMID- 2306640 TI - Morphometric evidence from C-synapses for phased Nissl body response in alpha motoneurones retrogradely intoxicated with diphtheria toxin. AB - Diphtheria toxin (DTX) kills cells by inactivating ribosomal translocation and when used to retrogradely intoxicate cat intercostal motoneurones produces marked morphological alterations in Nissl bodies, including those specifically sited postsynaptic to C-type axon terminals. Here, qualitative examinations of 'intoxicated' postsynaptic Nissl bodies reveal a progressive structural alteration marked by rER dilatation, rER lamellae fragmentation but retention of both the highly ordered multilamellate organization and ribosomal attachment until final stages of Nissl body dissolution. Morphometric results identified 3 broad phases to the postintoxication response which differed in the degree of rER cisternal dilation, and the numerical and spatial relationships between rER lamellae, rER-bound ribosomes and rER-associated polyribosomes. These phases reflect the known molecular basis of diphtheritic toxicity and contrast with the fast developing Nissl body reaction associated with the neurotoxin ricin which also invokes ribosomal dysfunction and has been used to mimic certain features of motor neurone disease. The cytopathology of DTX and ricin are compared in the Discussion. PMID- 2306641 TI - Electrophysiological properties of rat septal region neurons during development in culture. AB - We report on the development of membrane properties of septal region neurons from embryonic rats in serum-free culture during 1-25 days in vitro (DIV). Na(+) dependent action potentials could be evoked within 1 day after plating and 3 different types of outward current were observed by means of the patch-clamp technique: IK, IA and IC. In some neurons the neurotransmitter GABA evoked a chloride current after 2 DIV. In addition a cationic current elicited by glutamate appeared after 4 DIV. Within 8-12 DIV virtually all neurons were sensitive to both GABA and glutamate. Spontaneous action potentials and postsynaptic potentials occurred after 7-10 DIV but cultured septal neurons did not generate any pacemaker-like activity. PMID- 2306642 TI - In vivo intracellular analysis of rat dentate granule cells. AB - In vivo intracellular recordings and dentate EEG were obtained in urethanized curarized rats. Granule cells (GCs) were identified by antidromic activation as well as by intracellular staining with Lucifer yellow (LY). GCs fired spikes which, in 43.6% of the cases, had brief post-hyperpolarization. Slow spikes were recorded at hyperpolarized levels during the rebound of hyperpolarizing pulses or during inhibitory postsynaptic potentials (IPSPs). Medial septal nucleus or perforant pathway stimulation evoked an excitatory postsynaptic potential (EPSP) IPSP sequence. During theta (theta) rhythm, the membrane potential of 80.3% of the GCs showed rhythmic sine-like waves of up to 15 mV at a theta frequency which were phase-locked with extracellular theta. GCs were classified into 3 types: type 1 (67.1%) showed intracellular theta and rhythmic firing; type 2 (13.2%) revealed intracellular theta and random firing, but spikes tended to occur at a preferred phase of the dentate theta; and type 3 (19.7%) had neither intracellular theta nor rhythmic firing. Intracellular theta amplitude was wider during injection of the hyperpolarizing current and narrower during depolarizing ones, indicating that rhythmic EPSPs contribute to theta genesis. Intracellular theta was unaffected by Cl- or Cs+ diffusion, suggesting that IPSP is not essential to theta genesis. PMID- 2306644 TI - Clinical research in critical care. PMID- 2306645 TI - The need for nurse involvement in critical care research. PMID- 2306643 TI - Discharge patterns of laryngeal motoneurones in the cat: an intracellular study. AB - In decerebrate cats, stable intracellular recordings were made from 37 laryngeal motoneurones, the membrane potentials of which varied in relation to respiration. These motoneurones were identified as laryngeal since all were antidromically activated by stimulation of the recurrent laryngeal nerve, but in two, the antidromic activity could only be elicited by vagal stimulation (vagotomized cats). The cell bodies were all located within the nucleus ambiguous. Sixteen cells were depolarized during the phrenic burst and were classified as inspiratory laryngeal motoneurones (ILM). They repolarized at end-inspiration and received two successive waves of postsynaptic inhibition during expiration: an early, strong one and a late (end-expiratory), weaker one. The decay of the first wave was related to the duration of postinspiratory phrenic activity. Twenty-one cells depolarized abruptly in early expiration followed by a more-or-less gradual repolarization. They were classified as expiratory laryngeal motoneurones (ELM). All ELM were strongly inhibited during inspiration. Some of them received weak inhibition during end expiratory phase. The rapid and large depolarization observed during early expiration (and consequent maximal discharge frequency) can be explained by two summating mechanisms: a postinhibitory rebound resulting from the removal of inhibition during inspiration, and an excitatory phenomenon of unknown origin. The amplitude of this excitatory phenomenon was largest in cats with the most residual (early expiratory) phrenic activity. To explain the hyperpolarizations occurring in ELM during late expiratory and inspiratory phases and those occurring in ILM during early expiration, we hypothesize that reciprocal inhibition exists between networks controlling ILM and ELM activities or between these motoneurones themselves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306646 TI - Preparing for the human subjects review. PMID- 2306647 TI - Reliability and validity of physiologic measurement. PMID- 2306648 TI - Development of instruments to measure physiologic variables in clinical studies. PMID- 2306649 TI - Strategies for conducting clinical nursing research in critical care. PMID- 2306650 TI - My role as research nurse coordinator. PMID- 2306651 TI - The impact of machines on the work of critical care nurses. PMID- 2306652 TI - An effort to identify the optimum method of patient care delivery. PMID- 2306654 TI - Control of postoperative hypothermia in cardiovascular surgery patients. PMID- 2306653 TI - Effects of ethical dilemmas on stress felt by nurses providing care to AIDS patients. PMID- 2306655 TI - The effect of regular turning on CABG patients. PMID- 2306656 TI - Position and reference level for measuring right atrial pressure. PMID- 2306657 TI - Protocol for prevention of unintentional extubation. PMID- 2306659 TI - Effects of high dietary sulfur on brain functions using evoked potentials technique. AB - Brain stem auditory-evoked response (BAER) is a noninvasive technique used for detecting neurophysiological abnormalities of the brain stem along the auditory pathway. Brain stem auditory-evoked response recordings were obtained from subcutaneous skin electrodes from two control sheep and 22 other sheep fed high sulfur (S) diets with low or high concentration of thiamine (B1), copper (Cu), and molybdenum (Mo). At least four peaks (I,II,III,IV) of varied amplitude were observed in all animals. Neurophysiological abnormalities due to decreased conductivity and/or excitability of nerve fibers along the auditory pathway were found on the BAER recordings of sheep fed high S diet. Abnormalities of peaks and interpeak latencies within BAER recordings were related to histopathological observations of brain stem lesions. Lesions in the areas of the cochlear nuclei and lateral lemniscus were seen in conjunction with altered BAER components. However, abnormalities in BAER recordings and lesions in the brain stem also occurred in the absence of overt clinical signs. Analysis of interpeak latencies between peaks I and IV revealed significant differences among dietary groups. Sheep given diets low in Cu, Mo, and B1 were affected most. Factorial analysis indicated B1 and interactions among Cu, Mo, and B1 as significant factors influencing interpeak latencies. PMID- 2306658 TI - Activation of bovine monocytes and neutrophils by the Bb fragment of complement factor B: demonstration by the uptake of 3H-deoxyglucose. AB - The Bb fragment is the enzymatically active split product of bovine complement factor B. The Bb fragment was obtained after zymosan treatment of fresh bovine serum and fractionation of the treated serum, first over diethylaminoethyl Sephacel and then over an affinity column made up of monoclonal antibody to bovine Bb, coupled to cyanogen-bromide-activated Sepharose. Purified Bb has a molecular weight of 64,000, as determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The ability of purified Bb to activate phagocytes was assessed. The activation assay was based on the principle that the primary source of energy for the phagocytes is obtained from glucose. 3H deoxyglucose, a nonmetabolizable analogue of glucose, was used to obtain the quantitative measurement of the activation process. The activation by Bb was shown by the uptake of the labelled deoxyglucose in the phagocytic cells and was comparable to the activation caused by phorbol myristate acetate and N-formyl-L methionyl-L-leucyl-L-phenylalanine, run in parallel. These data showed that fragment Bb activates bovine monocytes and neutrophils and also suggested that, when generated after complement activation, Bb may stimulate monocytes and neutrophils for enhanced phagocytosis. PMID- 2306660 TI - An attempt to determine the tissue origin of equine serum alkaline phosphatase by isoelectric focusing. AB - The main purpose of this study was to ascertain whether isoelectric point determination of alkaline phosphatase (AP) using an isoelectric focusing technique on agarose gels could define the isoenzymes present in healthy equine serum. The isoelectric points of AP extracted from nine tissues ranged from pH 3.5 to 7.5 with all tissues having multiple bands. There was considerable similarity in band pattern among tissues, with only pancreatic and colostral AP having substantially different isoelectric points from the others. Sera contained thirteen bands with isoelectric points ranging from pH 3.5 to 6.2 and as each band was common to more than one tissue it was not possible to define the tissue origin of these by direct comparison with tissue patterns. The intensity of all serum bands declined as foals aged, with the greatest decrease in bands 4 and 5 (numbered from the anode). There was no relative change in the banding pattern between early and late pregnant mares or in the sera of two foals before and after ingestion of colostrum. The mean (+/- SD) total serum AP activities of young foals (1676 +/- 1100 IU/L), three month foals (402 +/- 64 IU/L) early pregnant (190 +/- 54 IU/L) and late pregnant mares (109 +/- 26 IU/L) were significantly different from each other whereas colostral ingestion in two neonatal foals had no effect. We concluded that equine AP is a very heterogeneous protein and that normal horse sera do not contain significant renal or small intestinal derived AP. However isoelectric focusing alone could not differentiate bone from liver derived AP in sera. PMID- 2306661 TI - The isoelectric focusing properties of serum alkaline phosphatase in disease and following prednisolone and phenylbutazone administration in the horse. AB - This study was undertaken to ascertain if the isoelectric focusing pattern of serum alkaline phosphatase (AP) from sick horses with high activity is useful for determining its tissue origin. The effect of oral prednisolone and phenylbutazone therapy on this enzyme in healthy horses was also investigated. The sick horses were divided into three groups: hepatic, intestinal and miscellaneous. All sera had approximately thirteen bands of AP activity when focused on agarose gels with a pH gradient of 3.5 to 9.5. All the horses in the liver disease group had greater than 65% of enzyme activity in bands 3 to 7 (counted from the anode) whereas the other two groups had at least 30% and up to 80% of activity in bands 8 to 13. This was true even in the several cases of primary intestinal disease that had additional biochemical evidence of liver damage. All bands were heat sensitive indicating that little if any AP was of small intestinal or renal origin. Oral prednisolone and phenylbutazone for 20 and 12 days respectively had no affect on serum AP activity or isoelectric pattern. We concluded that the AP in bands 3 to 7 is of liver origin but the origin of bands 8 to 13 remains undetermined although small intestinal or renal origin is unlikely. Isoelectric focusing of serum AP shows promise in differentiating cases of primary from secondary liver disease but further studies are required correlating serum patterns and tissue patterns in animals with diseases. PMID- 2306662 TI - Pharmacokinetics of phenobarbital in the cat following intravenous and oral administration. AB - Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three compartment models. After statistical comparison of the three models, a two compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat. PMID- 2306663 TI - A guinea pig model of bovine pneumonic pasteurellosis. AB - The induction of pneumonic pasteurellosis in guinea pigs (Cavia porcellus) was examined. Specific pathogen free male guinea pigs were anesthetized and a tracheostomy performed to introduce 10(5), 10(4) or 10(3) Pasteurella haemolytica A1 into the left principal bronchus. The surgical site was closed with tissue adhesive and staples and the animals were monitored for signs of respiratory tract infection. Within 24 hours after inoculation they became depressed, anorectic, pyretic and dyspneic. Fibrinous pleuropneumonia with prominent areas of necrosis and hemorrhage was present. Pericardial effusion was a frequent finding. There was infiltration of the pleura and alveoli with degenerate heterophils and macrophages, a hyperplastic mesothelium and fibrin exudation on the pleura and within alveoli. Hemorrhage, congestion, consolidation, edema and fibrin exudation were prominent in the hilar region of the lungs. Bacterial colonies were evident in all airways. More bacteria were recovered from infected lungs than were inoculated (p less than 0.05) indicating P. haemolytica was actively multiplying in the lungs. Hematological and clinical chemistry data were consistent with fibrinous pneumonia, however, blood cultures were positive for P. haemolytica in 61% (11/18) of animals sampled. Examination of pneumonic pasteurellosis in guinea pigs may be useful in studying pathogenetic and pathological features applicable to bovine pneumonic pasteurellosis (shipping fever pneumonia). PMID- 2306664 TI - Granulocyte plasma membrane damage by leukotoxic supernatant from Pasteurella haemolytica A1 and protection by immune serum. AB - Bovine respiratory disease caused by Pasteurella haemolytica may be partially mediated by a leukotoxin secreted by the microorganism. We examined the effect of leukotoxic Pasteurella supernatants on leakage of the cytosol enzyme lactate dehydrogenase and the lysosomal enzyme arylsulfatase from bovine granulocytes. Lactate dehydrogenase release (94%) was much higher than arylsulfatase release (38%) over 30 minutes of incubation. The Pasteurella supernatants inhibited superoxide production by stimulated granulocytes at concentrations which also caused substantial cell death as measured by failure to exclude trypan blue. Both toxic effects were prevented by serum from aerosol-immunized calves, and protection appeared to be antibody-specific by comparison with fetal bovine serum or with serum absorbed against intact P. haemolytica. These findings suggest that the leukotoxin may selectively disrupt the granulocyte plasma membrane, and that antibody directed against a surface component of the microorganism is also capable of protecting against the leukotoxin effect. PMID- 2306665 TI - Ovine ceroid-lipofuscinosis is a proteolipid proteinosis. AB - The pathogenesis of the ceroid-lipofuscinoses, inherited storage diseases of children, was studied in an ovine model. This was shown to have clinical and pathological features most in common with the late infantile and juvenile human forms of the disease. The ability to study sequential changes allowed the retinal lesions to be described as a dystrophy of photoreceptor outer segments which preceded loss of the photoreceptor cells. An early decrease in amplitude of the c wave electroretinograph was attributed to a decrease in the transpigment epithelial component. The decreased a- and b-wave amplitudes were attributed to the changes in and loss of, photoreceptor cells. The chemical components of isolated storage cytosomes were analyzed and shown to consist mostly of protein. Sequence analysis of the dominantly stored protein showed that it was identical to the DCCD reactive proteolipid or subunit c of mitochondrial adenosine triphosphate synthase and that it comprised approximately 50% of storage material. Based on the adage that the dominantly stored species should reflect the underlying biochemical anomaly, it was concluded that it was of pathogenic significance. This highly hydrophobic protein tends to extract with lipids in chloroform/methanol and is thus known as a proteolipid. Some of the remainder of the stored proteins also had this characteristic. It was concluded that ovine ceroid-lipofuscinosis was a proteinosis, more specifically a proteolipid proteinosis and as such it forms the prototype of a new class of storage diseases. Recognition of the nature of the dominantly stored chemical species has helped understanding of a variety of chemical and physical characteristics attributed to the whole pigment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306666 TI - The effect of Pasteurella haemolytica and the leukotoxin of Pasteurella haemolytica on bovine lung explants. AB - Bovine lung explants were used in a study designed to compare the pathogenic effects of Pasteurella haemolytica type 1, a nonpathogenic organism Neisseria subflava, or the crude leukotoxin of P. haemolytica on alveolar macrophages and lung parenchymal cells. Concentrated, purified peripheral blood neutrophil suspensions were added with the bacteria to some explants. Duplicate pairs of cultures from each treatment group were fixed at regular intervals up to 24 hours after seeding and morphological changes were assessed by light and electron microscopy. Pasteurella haemolytica caused deterioration of alveolar macrophages within one hour but did not affect parenchymal cells for more than 12 hours. Neisseria subflava did not affect alveolar macrophages initially, but caused an accelerated deterioration after four hours. After 24 hours, bacterial overgrowth caused similar deterioration of all cells in explants seeded with either bacterium. Alveolar macrophages phagocytosed large numbers of N. subflava but rarely ingested P. haemolytica. Added neutrophils did not have any discernible effect on any of the explants and did not potentiate bacterial effects. Addition of crude leukotoxin of P. haemolytica to the culture medium significantly accelerated alveolar macrophage deterioration without apparent effect on parenchymal cell survival. These results support the hypothesis that the severe tissue destruction of fulminant pneumonic pasteurellosis is not a direct result of bacterial infection. PMID- 2306667 TI - Host response to Pasteurella multocida turbinate atrophy toxin in swine. AB - A porcine strain of Pasteurella multocida (serotype D:3) produced a toxin causing turbinate atrophy (TA) in pigs. The toxin (TAT), processed on a high performance liquid chromatography size exclusion column, eluted as a single peak (molecular weight of about 160,000) containing trace amounts of endotoxin (lipopolysaccharide, LPS; protein:LPS, 85:1). The eluted fraction migrated on sodium dodecyl sulfate polyacrylamide gels as a single band. It could be prevented from dissociating into two prominent polypeptides by addition of a protease inhibitor. A single dose (2.0 to 79.0 micrograms/kg) of TAT given to pigs intravenously was lethal. Doses from 0.02 to 1.0 microgram/kg caused transient clinical signs of porcine systemic toxicosis with reduced appetite, generalized weakness, depression, lethargy, weight loss, and in some instances, death. Intradermal doses of TAT (greater than or equal to 0.1 microgram/site) produced hemorrhagic areas within four hours. Systemically, TAT causes bilateral TA, lymphopenia, liver dysfunctions, and possible renal impairment. Affinity of TAT for cells of epithelial origin was demonstrated in mice given 125I-TAT. In vitro, TAT stimulated DNA and protein syntheses of peripheral blood lymphocytes and suppressed syntheses in turbinate and kidney cell cultures without being cytolytic. Biological effects of TAT were eliminated by exposure to either heat, trypsin or anti-TAT antibody. PMID- 2306668 TI - Streptococcus suis infection in swine. A sixteen month study. AB - A total of 349 isolates of Streptococcus suis retrieved from different tissues from diseased pigs were examined in this study. Only 48% of them could be categorized as one of serotypes 1 to 8 and 1/2. Among typable isolates, serotype 2 was the most prevalent (23%), followed by serotype 3 (10%). The majority of all isolates originated from lungs, meninges/brain, and multiple tissues. Forty-one percent of typable isolates and 33% of untypable isolates were retrieved in pure culture. Other isolates were found in conjunction with Pasteurella multocida, Escherichia coli, Actinobacillus pleuropneumoniae, Actinomyces pyogenes, and other streptococci. Typable S. suis isolates were more frequently isolated from pigs between five and ten weeks of age, while untypable isolates were mostly found in animals aged more than 24 weeks. No obvious monthly and/or seasonal variation of the prevalence of isolation of S. suis could be detected. PMID- 2306669 TI - Prevalence of Streptococcus suis in four to eight week old clinically healthy piglets. AB - The study was undertaken to determine the prevalence, in the nasal cavities, of Streptococcus suis in four to eight week old clinically healthy piglets. Streptococci biochemically compatible with S. suis were isolated from 94% of piglets and 98% of farms. Of the 782 isolates submitted to serotyping, only 164 (21%) were included in the nine official serotypes. These 164 typable isolates originated from 121 (31%) of the 388 piglets and from 36 (73%) of the 49 farms included in the study. The most frequent serotypes found in piglets were, in decreasing order, 3, 4, 8 and 2. Serotype 1 was not detected in this survey. As many as 32% of piglets were found positive for two different serotypes and three different serotypes were found in 1%. PMID- 2306670 TI - Mutants of rabies viruses in skunks: immune response and pathogenicity. AB - In studies to develop an oral rabies vaccine for wildlife, the immune response to and pathogenicity of two types of mutants of rabies viruses were examined. Forty five small plaque mutants were selected from cultures of ERA rabies virus treated with 8-azaguanine or 5-fluorouracil and tested for pathogenicity in mice. Two of these mutants AZA 1 and AZA 2 (low pathogenicity in mice) were given to skunks by oral (bait), intestinal (endoscope) and intramuscular routes. Additionally, challenge virus standard (CVS) rabies virus and mutants of this and ERA rabies virus (CVS 3766 and 3713, and ERA 3629) that were resistant to neutralization by specific antiglycoprotein monoclonal antibodies (and apathogenic in mice) were tested by various routes in skunks. Skunks given AZA 1 and AZA 2 were challenged at three months postinoculation with street rabies virus. After oral administration, there were very low rates of seroconversion with AZA 1 and AZA 2 and on challenge only 2/7 given AZA 1 and 1/8 given AZA 2 survived. None of the skunks given the other mutants orally seroconverted. AZA 2 produced a high rate of seroconversion (8/8) by the intestinal route and all challenged skunks in this group survived (7/7). All skunks vaccinated intramuscularly with AZA 1 (4/4) or AZA 2 (4/4) developed high levels of rabies neutralizing antibodies and survived challenge. The mutant CVS 3766, while apathogenic when given intracerebrally to adult mice, was consistently pathogenic by this route (and intranasally) in skunks. These results demonstrate that skunks are highly resistant to oral immunization by live rabies virus vaccines and that pathogenicity (by intracerebral route) of the mutant CVS 3766 is markedly different in mice and skunks. PMID- 2306671 TI - A method to estimate the somatic cell count of milk from a mastitic quarter using composite somatic cell count. AB - The purpose of the study was to estimate the extent to which one quarter could be inflamed relative to the other three quarters of a cow, given that knowledge only of the composite milk somatic cell count (SCC) was available. An algebraic relationship, which incorporated the parameters of composite milk SCC, production loss associated with composite milk SSC, SCC of milk from an inflamed quarter, and SCC from three non-inflamed quarters, was used to derive hypothetical estimates of the SCC in one inflamed quarter. A simple case was considered in which one quarter was mastitic, the SCC in milk of the noninflamed quarters was equal, and there was no production compensation by the noninflamed quarters. Previously published estimates were used for production loss associated with composite milk SCC. For moderate composite milk SCC (300,000-500,000 cells/mL) and low-to-moderate SCC in milk of noninflamed quarters (100,000 cells/mL), the SCC of milk from one inflamed quarter was predicted to be very high, ranging from about 1.26 million (log10 SCC = 6.1) to 6.3 million (log10 SCC = 6.8) cells/mL, and compatible with signs of clinical mastitis. These results suggest that in order to screen cows with clinical mastitis in only one quarter, composite milk SCC should be considerably lower than values presented previously by other investigators. PMID- 2306672 TI - In vitro susceptibility of selected veterinary bacterial pathogens to ciprofloxacin, enrofloxacin and norfloxacin. AB - The minimum inhibitory concentrations (MIC) of ciprofloxacin, enrofloxacin, and norfloxacin were tested for approximately ten clinical isolates of each of Actinobacillus pleuropneumoniae, Actinobacillus suis, Actinomyces pyogenes, Corynebacterium pseudotuberculosis, Erysipelothrix rhusiopathiae, Haemophilus parasuis, Haemophilus somnus, Pasteurella haemolytica, Pasteurella multocida, Rhodococcus equi, Streptococcus equi, Streptococcus suis and Streptococcus zooepidemicus. Ciprofloxacin and enrofloxacin had similar activity and were more active than norfloxacin. All isolates had an MIC of 1.0 microgram/mL or less for ciprofloxacin and enrofloxacin, and these drugs had particularly marked activity against the gram-negative bacteria tested. PMID- 2306673 TI - Minimal inhibitory concentrations of antimicrobial agents against Actinobacillus pleuropneumoniae. PMID- 2306674 TI - Caprine beta-D-mannosidosis: characterization of a model lysosomal storage disorder. AB - Interest in using caprine beta-D-mannosidosis as a model to evaluate bone marrow transplantation in the treatment of human lysosomal storage disorders provided the stimulus for characterization of beta-D-mannosidase in selected goat tissues and induction of hemopoietic chimerism in the goat. Total beta-D-mannosidase activity was measured with the use of 4-methylumbelliferyl beta-D-mannopyranoside as substrate. Residual activity in mutant liver was 52% of control but no activity was detectable in mutant kidney or brain tissue. Normal adult goat liver contained two forms of beta-D-mannosidase, a nonlysosomal form (52%) with a broad pH range for optimum activity (4.5-8.0) and a lysosomal form (48%) with a pH optimum of 5.5. Residual enzyme in mutant liver consisted entirely of the nonlysosomal form. Normal adult thyroid, kidney and brain contained two major lysosomal isoenzymes with pIs 5.5 and 5.9 and traces of a minor isoenzyme with pI 5.0. Normal liver contained three isoenzymes with similar pIs; however, an isoenzyme with pI 5.0 predominated. In 60-day fetal liver lysosomal isoenzymes predominated and only trace amounts of nonlysosomal isoenzyme were detectable. Total hepatic beta-D-mannosidase activity increased towards adult levels during the last 90 days of gestation as a result of increasing nonlysosomal isoenzyme activity. Intraperitoneal injection of fetal liver cells into 60-day goat fetuses resulted in sustained hemopoietic chimerism in surviving kids without evidence of graft-versus-host-disease. These results suggest that transplantation of normal fetal liver cells into preimmunocompetent goat fetuses affected with beta-D mannosidosis is feasible and may provide an alternative strategy for evaluation of postnatal bone marrow transplantation in the treatment of human lysosomal storage disorders. PMID- 2306675 TI - Hereditary canine spinal muscular atrophy: canine motor neuron disease. AB - Motor neuron diseases, manifest as weakness and atrophy of skeletal muscles, occur in infancy, childhood, and adult life. Some forms of this disease are inherited. Motor neurons are selectively affected and exhibit cytoskeletal pathology, primarily enlargements of proximal axons by accumulations of transported neurofilaments. A motor neuron disease, hereditary canine spinal muscular atrophy, has been discovered in Brittany spaniels. The disease is inherited as an autosomal dominant characteristic and shows striking clinical and pathological features in common with human motor neuron disease. The availability of this excellent animal model of the human condition has allowed neurobiological investigations of the dynamics of structural and chemical pathologies of vulnerable neurons. PMID- 2306676 TI - The Sertoli cell of the water buffalo--an electron microscopic study. AB - The ultrastructure of Sertoli cells in the seminiferous tubules of water buffaloes before and during sexual maturity was studied by transmission electron microscopy, with emphasis on the intranucleolar vesicular elements. Sertoli cells of animals under 12 months of age were distinguished from the germ cells by the presence of electron dense membrane bound bodies within their cytoplasm. These cells, referred to as basal indifferent supporting cells, were probably involved in the phagocytosis and elimination of degenerating spermatocytes, which failed to differentiate into spermatids and spermatozoa in animals under one year of age. In 12 month old animals, a few Sertoli cells exhibiting the vesicular elements appeared in the nucleolar region while in animals over 15 months of age Sertoli cells could be positively identified by the characteristic cytoplasm containing microtubules, elongated and electron dense mitochondria, extensive granular endoplasmic reticulum and the presence of spermatids in various stages of spermiogenesis. The vesicular elements in the nucleolar region of the Sertoli cells were most prominent at this stage. Ultrastructural features of the Sertoli cells revealed an abundance of ribosome-like particles surrounding the vesicles of varying size. Some of these vesicular elements contained amorphous material suggesting that they represent the products sequestered in the nuclear region for transport to the cytoplasm and that the process of spermiogenesis may be dependent on the ability of Sertoli cells to generate these products at sexual maturity. PMID- 2306677 TI - An evaluation of the multiple-breath nitrogen washout as a pulmonary function test in horses. AB - Multiple-breath nitrogen washouts (MBNW) were performed with 29 light horses. Seven normal horses were used to examine the reproducibility, and 22, ranging from normal to severely diseased, were used to examine the changes in chronic obstructive pulmonary disease (COPD) and the effect of a bronchodilator, salbutamol, on the distribution of ventilation. The MBNW were analyzed using the functional residual capacity (FRC), end-tidal N2 concentration of the final breath of the MBNW (FETN2,fb), end-tidal N2 concentration when the cumulative expired volume was equal to body weight (FETN2,bw), lung clearance index (LCI), Becklake index (BI), mixing ratio (MR), index of distribution of inspiration (IDI), pulmonary N2 clearance delay (PCD) and ventilatory efficiency (EFF). The LCI, MR, IDI, PCD and EFF were calculated at end-tidal N2 concentrations (FETN2), equal to 3%, 2% and FETN2,fb. The EFF was also calculated at FETN2 = 8%, as was BI. The within day coefficient of variation for most indices of the MBNW was 10 15%. None of the indices varied significantly from day-to-day. The FETN2,fb, FETN2,bw, MR, IDI, PCD, and EFFfb, EFF3% and EFF2% differed between the horses with COPD and the normal horses, and all of the indices, except FRC, were correlated with a histopathological score of the small airways. The FETN2,bw appeared to be the most sensitive index in detecting the horses with COPD. In the horses with COPD, salbutamol caused a decrease in FRC and FETN2,fb indicating increased ventilation of the lung. However, LCI increased suggesting a less efficient distribution of ventilation. PMID- 2306678 TI - An in vitro chemosensitivity test for the screening of anti-cancer drugs in childhood leukemia. AB - We applied the MTT dye reduction assay to the anti-cancer drug sensitivity test using short-term microplate cultures. Blast cells were cultured with approximately 25 anti-cancer drugs for 4 days. After cultivation, MTT dye was placed in each well, and the formazans generated by living cells were dissolved in acidified isopropyl alcohol. The absorbance of each well was measured at a scanning microplate photometer. When we made the table of the cytotoxicity index (CI) that was classified into anti-cancer drugs and concentrations for each leukemic sample, it was possible to compare efficacy with different drugs and to select the effective ones. Retrospectively, the in vitro results were compared with the clinical responses of the 34 patients (26 of acute lymphocytic leukemia [ALL] and eight of acute nonlymphoblastic leukemia [ANLL]) who were treated by combination chemotherapy. The following results were obtained: true-positive rate, 78.1%; true-negative rate, 57.1%; and predictive accuracy, 74.4%. Therefore, the MTT assay-CI table might serve as a reliable tool for the selection of effective chemotherapy in patients with acute leukemia. PMID- 2306679 TI - Endoscopic localization of the squamocolumnar junction before cervical cone biopsy in 284 patients. AB - A preoperative examination of the endocervical canal was performed in 284 patients scheduled for excisional cone biopsy because of abnormal cervical cytology and unsatisfactory colposcopy. The information obtained regarding the depth of the new squamocolumnar junction (SCJ) was used to tailor the length of the cone specimen in an attempt to remove the entire transformation zone (TZ), and was associated with a low rate of incomplete disease excision. An analysis of the data generated by this study indicates that the position of the new SCJ is influenced by age, menopausal status, and the use of estrogen-containing medication. PMID- 2306680 TI - Squamous cell carcinoma antigen in the diagnosis and treatment follow-up of oral and facial squamous cell carcinoma. AB - The squamous cell carcinoma (SCC) antigen was determined by radioimmunoassay in the serum of 40 untreated patients with SCC of the oromaxillofacial region. The mean (+/- SEM) serum concentration for these patients (3.8 +/- 0.8 ng/ml) was significantly higher than that of 52 disease-free patients coming to routine postoperative care (1.2 +/- 0.1 ng/ml) and of 74 healthy controls (1.1 +/- 0.07 ng/ml). Using a arbitrary limit of 2.2 ng/ml, pathologic serum levels of SCC were observed in 15 (38%) of 40 untreated patients, whereas only four (7.7%) of 52 tumor-free patients revealed an elevated serum SCC. Serial measurements of SCC were pretherapeutically available in 28 patients as well as during individual therapy and further follow-up. All but one of these patients had a normal serum SCC postoperatively. The authors' results demonstrate that the clinical value of SCC lies mainly in monitoring the course of the disease. Careful follow-up studies should be undertaken to determine whether serial determination of SCC is promising in early prediction of tumor reoccurrence. PMID- 2306681 TI - Recombinant alpha-2b-interferon enhances the circulating levels of a 90 kilodalton (K) tumor-associated antigen in patients with gynecologic and breast malignancies. AB - The circulating levels of a 90-kilodalton (K) tumor-associated antigen were measured in the blood of 43 patients with gynecologic and breast malignancies who underwent a short course of recombinant alpha-2b-interferon (rIFN alpha-2b) (3 million U/m2/d intramuscularly [IM] for 3 days). Of the 43 patients, 23 showed abnormal 90-K levels (greater than 1.7 U/ml). A significant increase of antigen levels was already observed 24 hours after the first administration and persisted throughout the investigation period. Of 20 patients with 90-K levels below the normal limit, 12 went over the normal cutoff value after two rIFN alpha-2b injections. No significant modifications of 90-K levels were detected in nine women receiving rIFN alpha-2b for the treatment of genital condylomata. The serum levels of two other tumor-associated antigens, CA 125 and CA 15-3, were not modified by rIFN alpha-2b administration. The ability of rIFN alpha-2b to increase the circulating levels of 90-K might have important clinical implications for the serodetection of cancer. PMID- 2306682 TI - An analysis of immunocomplexes for the detection of the early stages of colon cancer. AB - A radioimmunoassay was developed for the detection of the early stages of colon cancer by analysis of immune complexes (IC) with a specific polyclonal antibody. Human colon cancer cells were grown in a capillary culture system to provide unaltered antigens for the development of a specific antibody. The antibody was labeled with iodine 125 (125I) and used to analyze the antigen component of IC removed from whole serum. The assay was positive in 50% and 88% of known Dukes' A and Dukes' B colon cancer patients, respectively. It was also positive for only 25% of Dukes' C and 14% of Dukes' D patients, possibly because of the decreased quantity of specific IC found in the late stages of colon cancer. A blind study of patients referred for colonoscopy compared pathology diagnosis with the test results. The assay was positive for one patient with a polypoid adenocarcinoma (Dukes' B) and one with a villous adenoma and negative for 38 patients with benign polyps and 43 with no polyps. The assay was negative for all patients with stomach cancer and inflammatory bowel diseases and positive for about 10% of the patients with pancreas or breast cancer. The results of this preliminary investigation suggest that this radioimmunoassay may be useful for the detection of the early stages of colon cancer. PMID- 2306683 TI - The unbalanced 1;7 translocation in de novo myelodysplastic syndrome and its clinical implication. AB - In our chromosome study of 97 patients with myelodysplastic syndrome (MDS), six showed an unbalanced translocation between chromosomes 1 and 7 [-7, +der(1)t(1;7)(p11;p11)]. All of them had morphologic myelodysplasia in trilineage of bone marrow cells, and cytopenia was the major finding in the peripheral blood. All six patients had symptoms of infection at the time of diagnosis, and five showed immunologic abnormalities (polyclonal hypergammaglobulinemia in four and increased marrow plasma cells in three). None of the patients survived more than 11 months after the diagnosis; the median survival time was 4 months. Both of the two patients whose karyotypes were reexamined in the course of their disease showed karyotypic evolution accompanying the coincidental leukemic transformation. Six patients with MDS who had the same chromosome abnormality [t(1;7)] are described and their characteristic clinical features are presented. PMID- 2306684 TI - A comparative analysis of nuclear DNA content and N-myc gene amplification in neuroblastoma. AB - Nuclear DNA content and N-myc amplification have been found to have prognostic significance in neuroblastoma. To investigate the interrelationships between these two parameters, tumor samples from 18 patients with neuroblastoma were analyzed for both total DNA and N-myc gene content. Quantitative DNA analysis was performed by image analysis. Quantitative Southern blot hybridization was used to determine N-myc gene copy number and to distinguish between low level gene amplification or excess gene copies secondary to aneuploidy. Six of the 18 patients have died. Five of the six had nonaneuploid tumors, but only two of the six exhibited major N-myc amplification. Low-level amplification was detected in one Stage II patient. The authors' results suggest that neuroblastomas with N-myc amplification are a subset of nonaneuploid tumors. PMID- 2306685 TI - Distribution of fibronectin and laminin in human thymoma. AB - The distribution of fibronectin and laminin, two extracellular matrix and basement membrane components, was studied in 55 cases of thymoma using immunohistochemistry. The results were compared according to histologic type or clinical stage of the tumor. In addition, electron microscopic observation was done to clarify the extracellular structure of thymoma. Two staining patterns were seen. First, a diffusely or partially intricate network of fibers that contained fibronectin and laminin surrounded tumor cells in 21 out of 55 cases. Most of these cases were spindle cell thymomas and showed low invasive tumors. Second, fibers that contained fibronectin and laminin were restricted only to the septa, blood vessels, and perivascular spaces that did not show a network in the remaining 34 cases. Polygonal cell thymomas showed the latter staining pattern and these were more invasive tumors. We conclude that this network is a characteristic structure of spindle cell thymomas and is related to the invasiveness of the tumor. PMID- 2306686 TI - Sex hormone receptors in gastric cancer. AB - Gastric adenocarcinoma that originates from mucosal tissue invades submucosa, muscle, and serosa in different stages. The level of progesterone receptors (PgR), estrogen receptors (ER), and androgen receptors (AdR) in the superficial part of gastric cancer tissues (CAs) from 16 patients was determined and compared with that of the corresponding normal gastric mucosal tissues (NLm). There were PgR in all CAs (100%) with values that ranged from 20.5 to 548.4 fmol/mg protein. Eight CAs (50%) had ER values that ranged from 6.8 to 325.1 fmol/mg protein. AdR was found in two CAs with values of 14.7 and 16.4 fmol/mg protein. In NLm, 15 (93.8%) had PgR values that ranged from 7.3 to 473.2 fmol/mg protein and ten (62.5%) had ER values that ranged from 0.9 to 87.9 fmol/mg protein. AdR were present in two NLm with values of 1.5 and 73.5 fmol/mg protein. There was no statistical difference in levels of PgR and ER between CAs and NLm. There were PgR in all gastric cancers and in 93.8% of NLm. The results suggest that gastric mucosa may be the target tissues for progesterone action. Furthermore, the lack of correlation between the levels of ER and PgR in gastric cancer tissue suggests that the PgR in gastric cancers are probably estrogen independent. PMID- 2306687 TI - Low-grade intraosseous osteosarcoma. AB - A study of 80 well-differentiated osteosarcomas, 16 from the Mayo Clinic files and 64 from our consultation files, revealed that males and females were about equally affected, most of the patients were young adults, and skeletal distribution was similar to the distribution seen in conventional osteosarcoma. Radiographs generally showed poor margination, suggestive of malignancy. Histologically, the tumors were composed of spindle cells with only minimal atypia. Some tumors had bone spicules similar to those seen in fibrous dysplasia. An invasive growth pattern was the most helpful feature in differentiating low grade osteosarcoma from fibrous dysplasia. Initial treatment was highly variable. Local excision was almost always associated with recurrence. Wide excision was almost never followed by recurrence. The recurrent tumor was a high-grade, conventional osteosarcoma in 15% of the patients, and this was associated with a poor prognosis. Wide excision seems to be the treatment of choice for this very rare variant of osteosarcoma. PMID- 2306688 TI - Primary nasal-paranasal oropharyngeal lymphoma in the pediatric age group. AB - Nasal-paranasal oropharyngeal (NPOP) non-Hodgkin's lymphoma (NHL) is a disease of the very young (median age, 5 years) and of the aging adult (median age, 50-60 years). Of a total of 208 pediatric patients with NHL studied, 20 (9.6%) had primary NPOP. Sixty percent of the patients had Stage I and II disease. Primary sites were maxillary sinus in eight patients; tonsils in eight; posterior pharynx in two; mandible in one; and orbit in one patient. Histologically, the disease is different than that of the adults since most patients had B-cell lymphomas of the diffuse undifferentiated type (Rappaport) or small cell non-cleaved types (Lukes Collins, Kiel, and Working Formulation). None of these patients had gastrointestinal involvement. All patients were treated with the LSA2-L2 regimen and radiation therapy was given to primary unresectable tumors and regional metastases. The lymphoma event-free survival was 75%, with a median observation period of 99+ months. In staging systems that refer mostly to amount of disease outside of the primary (such as ours, Murphy's, and the Ann Arbor staging systems) stage did not correlate well with disease-free survival. In the TNM staging of 1977, a staging system that refers to size of primary tumor as well as regional and systemic disease, stage correlated better with prognosis and survival. In our staging system, eight of 12 patients (66.7%) with Stage I and II disease; four of four with Stage III; two of two with Stage IVA; and zero of two with Stage IVB survived. In the TNM staging system, three of three patients with Stage II and III disease and 12 of 18 patients (67%) with Stage IV disease survived. All recurrences occurred early suggesting that early intensification of chemotherapy may produce better results. PMID- 2306689 TI - Malignant mesothelioma in young adults. AB - Ten cases of malignant mesothelioma presenting in patients 40 years old or younger at diagnosis were reviewed. Seven cases had a documented history of asbestos exposure of which five were household exposures. The median age at first exposure to asbestos was 10 years and the median duration of exposure was 120 months. The median latency period (time between initial asbestos exposure and diagnosis of malignant mesothelioma) was 19 years. The median interval from initial symptoms to definitive diagnosis was 5.5 months. The case history of each patient is presented. A significant delay in diagnosis in this age group compared with an age-unrestricted series is noted. The significance of nonoccupational exposure to asbestos is emphasized as a probable causative factor in the development of malignant mesothelioma. In addition, a possible genetic predisposition is briefly discussed. PMID- 2306690 TI - Cardiac metastases. AB - The authors found metastases to the heart in 10.7% of 1029 autopsy cases in which a malignant neoplasm was diagnosed. The lung was the commonest primary site (36.4%) and adenocarcinoma was the most frequent cell type (36.4%) of neoplasms metastatic to heart. Nonepithelial tumors accounted for 22.7% of cardiac metastases. Epicardium was involved in 75.5% of metastatic lesions and a pericardial effusion was present with 33.7% of epicardial metastases. Although hemorrhagic effusions occurred in only 12 cases with metastases to heart, these represented 76.4% of all such effusions. Lymphomas associated with the acquired immune deficiency syndrome showed the most extensive cardiac involvement. Primary sites and cell types of cardiac metastases have evolved over time and have been modified by chemotherapy, increased survival of cancer patients, increasing incidence of lung carcinoma, and recently by the acquired immune deficiency syndrome epidemic. PMID- 2306691 TI - Accuracy of cytology diagnosis. PMID- 2306692 TI - The optic nerve as the site of initial relapse in childhood acute lymphoblastic leukemia. PMID- 2306693 TI - Pseudocolor display of regional organ blood flow determined by means of the radioactive microsphere technique. AB - The measurement of regional blood flow (RBF) by means of the radioactive microsphere method yields large sets of raw data. In order to display this large volume of data, we have developed a program which provides the user with a graphical illustration of RBF in different organs (e.g., heart, kidney, brain) using various projections and sections. RBF is visualized by a pseudocolor representation. This set-up enables the user to perform a semiquantitative analysis of RBF and provides a tool for the compact representation of the spatial distribution of RBF values in different parts and layers of the organs being studied. The program runs on a standard microcomputer. PMID- 2306694 TI - An expert system for guiding image segmentation. AB - Application of image segmentation to biomedical research is now customary. Due to the existence of a rich heuristic knowledge, many users have no deep experience in this field. It is therefore necessary to integrate knowledge-based techniques with image segmentation operators. The purpose of our expert system is to guide users in image segmentation. Its main functions are: suggest a reasonable overall scheme of processing and recommend appropriate operators and algorithms at each stage. The characteristics of this expert system are presented: (a) interaction with users: through "conversation," the expert system acquires the informations about a given problem; (b) use of belief values which indicate users' descriptions about the image characteristics. By associating image features with belief values, the system gets the informations about the image appearance and makes inference more effectively; (c) local backtracking strategy, which allows the expert system to repeatedly search for a better solution until a satisfactory result is obtained; (d) integrating with an image analysis package, users can directly execute the operations recommended by the expert system. A practical application of the system is then shown in details. Finally, our opinions in designing such a system are discussed. PMID- 2306695 TI - Radiological laser film scanner sampling artifact. AB - Artifacts seen on laser digitized radiographs are analyzed and mathematically explained based on the concept of image contrast. Our investigation considered the following determinants: (a) laser spot size, (b) signal processing components, (c) image characteristics, and (d) observer performance. A functional relationship between the sampling interval, laser spot size, and the contrast of the artifact seen on the digitized image is derived. This relationship is verified experimentally using a variable spot size laser source and sampling at interval of 175.0 microns. The problem of digitizing artifact seen on film images obtained with anti-scatter grids is discussed. PMID- 2306696 TI - Three-dimensional surface reconstructions using a general purpose image processing system. AB - A general purpose two-dimensional (2-D) image processing software system was used to produce high quality three-dimensional (3-D) surface reconstructions from serial sections such as CT scan slices. Depth-encoded 3-D surface images, gradient-shaded 3-D surface images, and weighted sums of these two images were computed. Images that simulate transmission radiographs ("volumetric" views) were created from the same slice data. Hidden surfaces were displayed by reconstructing in 3-D only subvolumes of the original data set. The 2-D image processing functions used were limited to: planar subimage selection and merge, arithmetic and boolean operations, piecewise linear gray scale transform, convolution (1-D), and format conversion (byte-integer-float). Using these methods any user with a general purpose 2-D image processing system can analyze and view multi-slice data as 3-D volume and surface projections. PMID- 2306697 TI - The development of distant pulmonary infiltrates following thoracic irradiation: the role of computed tomography with dosimetric reconstruction in diagnosis. AB - High doses of external beam radiotherapy are required to obtain local control of many intrathoracic neoplasms. Because spinal cord tolerance limits the radiation dose that can be given through anterior and posterior fields, it is often necessary to increase the dose to the primary tumor site using oblique or lateral fields. When pulmonary infiltrates develop following treatment in these patients, it is frequently difficult to distinguish between infection, recurrent tumor, and radiation pneumonitis. In nine patients in whom acute pulmonary infiltrates occurred following a course of thoracic irradiation, computed tomography (CT) with computed dosimetric reconstruction (CDR) were studied in an attempt to correlate the treatment volumes with the location and configuration of the infiltrates and in this way establish the source for the pulmonary abnormalities. In seven of these patients, the diagnosis was changed, and the resulting post irradiation clinical therapy was altered as a consequence of this retrospective study. PMID- 2306698 TI - The chronic expanding intracerebral hematoma. AB - Three normotensive patients presented with seizures and CT showed an intracerebral hematoma. Although these patients had no more seizures and developed no other neurological deficit, repeat CT scans (performed 2 to 3 weeks later) showed hematoma enlargement. Angiogram was performed in 2 cases and showed no evidence of vascular malformation or neoplasm. Six weeks to 6 months later, CT showed that the hematoma had changed from a hyperdense to an isodense appearance and in two cases slight enhancement occurred. During a follow-up interval of 6 to 24 months, no other neurological episodes have occurred. The etiology of the chronic expanding intracerebral hematomas was not delineated in these 3 patients. PMID- 2306699 TI - MR imaging of acute subarachnoid hemorrhage. AB - The MR appearance of acute subarachnoid hemorrhage experimentally produced in Macaca monkeys and observed in patients with clinically documented acute subarachnoid hemorrhage is presented. Subarachnoid hemorrhages were produced in two Macaca Nemestrema monkeys using the technique of Frazee. CT and MR imaging were performed immediately after the procedure and at frequent intervals up to two week post hemorrhage. MR including T1 and T2 weighted multiplanar spin echo images were obtained. The imaging studies were compared with clinical evaluations and pathological specimens of all animals. Findings in the experimental animals are correlated with those observed in patients with clinically documented subarachnoid hemorrhage. The results show that acute subarachnoid hemorrhage (SAH) can be detected with MRI as isointense signal replacing normally black CSF spaces on T1 weighted images. Signal changes most likely relate to protein water binding associated with the clotting mechanism rather than oxidative denaturation of hemoglobin. Imaging performed experimentally and clinically beyond four days, however, showed a marked increase in signal intensity on T1 weighted images which probably does result from methemoglobin formation within the clot matrix. Although CT remains the gold standard in detecting acute SAH, MR does provide some sensitivity to its presence. PMID- 2306700 TI - Age-related changes in cerebral white matter measured by computed cranial tomography. AB - Changes in the cerebral white matter in relation to aging were studied quantitatively by computed cranial tomography (CT) in 70 healthy subjects aged 30 to 94 years. There were no age-related changes in the CT number of the white matter (WMCT) in 41 younger subjects aged 30 to 65 years. But, there was a significant negative correlation between age and the WMCT in 29 elderly subjects aged 66 to 94 years. Brain atrophy was significantly correlated with the WMCT. The WMCT decreased with aging even in neurologically healthy elderly persons. PMID- 2306701 TI - Central nervous system magnetic resonance imaging findings in neuro-Behcet syndrome. AB - In a patient with neuro-Behcet (N-B) syndrome, MRI images obtained with TR 2000 msec, and TE 80 msec showed an increased signal intensity in the brain stem corresponding to the neurological symptoms. In N-B syndrome, the brain stem has been documented as a main site of the lesion, and MRI shows promise as a useful technique in the diagnosis of this disease. PMID- 2306702 TI - CT appearance of bilateral, acute thrombosis of the main cerebral arteries. AB - Acute thrombosis within the lumen of the intracranial artery may occasionally be demonstrated on precontrast CT. The hyperdensity follows the course of the occluded segment of the vessel and an area of low attenuation in the territory of the involved artery is usually present, consistent with infarction. Usually, a single vessel is involved; occlusion of multiple branches occurs less commonly. This report demonstrates a case of diffuse bilateral thrombosis of the main arteries of the anterior circle of Willis. PMID- 2306704 TI - Antitumour principles from Ixora javanica. AB - The antitumour agent from Ixora javanica flowers shows broad activity against transplantable solid tumours (DLA) in mice by inhibiting the growth of tumour and arresting the growth of already formed tumours; with lesser activity against Ascites tumours. In vitro cytotoxic studies showed 50% cytotoxicity to Dalton's lymphoma (DLA) and Ehrlich Ascites tumour cells at a concentration of 12 micrograms and 65 micrograms, respectively, with no activity against normal lymphocytes but preferential activity for lymphocytes derived from leukemia patients (ALL) (CML), and K 562 suspension cell culture. Tritiated thymidine incorporation studies indicated the mechanism of action of the agent at the site of DNA synthesis. The purified fractions contained Ferulic acid, Pyrocatacheuic acid and caffeic acid. PMID- 2306703 TI - Suramin blocks intracellular Ca2+ release and growth factor-induced increases in cytoplasmic free Ca2+ concentration. AB - Suramin, a polysulfonated naphthylurea with antitumor activity, has been shown to be an inhibitor of the release of Ca2+ from non-mitochondrial stores induced by the putative intracellular second messengers inositol 1, 4, 5-trisphosphate and GTP in saponin permeabilized Swiss 3T3 fibroblasts. The IC50 for the effect of suramin was about 40 microM in both cases. Suramin did not block Ca2+ release induced by the Ca2+ ionophore 4-bromo A23187 or by the membrane perturbing agent halothane. Suramin, 7 x 10(-5) M, caused a 49% decrease in the elevation of intracellular free Ca2+ concentration ([Ca2+]i) caused by platelet derived growth factor (PDGF) in intact Swiss 3T3 fibroblasts but did not block the increases in [Ca2+]i caused by bradykinin or vasopressin. Suramin decreased PDGF binding to its receptor on intact Swiss 3T3 fibroblasts but had no effect on the binding of bradykinin and vasopressin. The results show that the effect of suramin in decreasing the [Ca2+]i response to growth factors may be mediated by a block of growth factor-receptor binding, but an effect on intracellular Ca2+ release cannot be ruled out. PMID- 2306706 TI - Antitumor activity of brequinar sodium (Dup-785) against human head and neck squamous cell carcinoma xenografts. AB - The effect of Brequinar sodium on the growth of xenografts established from head and neck squamous cell carcinomas (HNSCC) was assessed. Brequinar sodium is a novel drug, known to inhibit dihydroorotic acid dehydrogenase (DHO-DH), resulting in a decrease of the pyrimidine de novo synthesis. The drug was administered i.p. to tumor-bearing nude mice, once a day, during 5 days at a maximum tolerated dose of 50 mg/kg/day. Statistically significant growth delaying effects were observed in 4 out of 5 lines tested. In 3 of these lines the effect was moderate and short lasting, whereas in one line (HNX-LP) tumor growth rate was totally inhibited for a 17-day period. In this line, Brequinar sodium was superior to 5 drugs known to be active in HNSCC patients. In two tumor lines DHO-DH activity could be measured and the results are in agreement with the concept that there is a relation between Brequinar sodium sensitivity and enzyme activity. PMID- 2306705 TI - Modulatory interaction between initial clofibrate treatment and subsequent administration of 2-acetylaminofluorene or sodium phenobarbital on glutathione S transferase positive lesion development. AB - The effects of 2-acetylaminofluorene (2-AFF) or sodium phenobarbital (PB) treatment subsequent to clofibrate (CF) administration in terms of preneoplastic lesion development and induction of hepatocellular carcinomas (HCC) were studied using Fischer 344 rats. Animals received CF (0.3% in diet) for the initial 30 weeks, and then either 2-AAF (0.01% in diet), PB (0.05% in diet) or basal diet until week 78. Further groups were initially given basal diet, and then treated with 2-AAF or PB week 30. Two-thirds partial hepatectomy was carried out on all animals at week 3, sacrifice of representative groups being performed at weeks 30, 48 and 78. No glutathione S-transferase placental form positive (GST-P+) or negative focal or nodular lesions were apparent at the cessation of CF administration. The induction of GST-P+ focal lesions by 2-AAF was markedly decreased at week 48 in the group previously given CF (P less than 0.05) and furthermore, the respective incidences of HCC at week 78 were 4/17 (23.5%) in the CF----2-AAF group and 7/17 (41.2%) in the 2-AAF alone case. No significant differences between CF----PB and PB alone groups were evident with regard to either GST-P+ lesions and HCC at weeks 48 and 78. No CF-specific GST-P negative neoplastic nodules or HCC were observed in any of the experimental groups. These results suggest that pretreatment with CF may inhibit the induction of GST-P+ focal lesions and HCC by subsequently administrated 2-AAF and that CF demonstrates no initiating activity for liver carcinogenesis under the present condition. PMID- 2306707 TI - Dose response of N-butyl-N-(4-hydroxybutyl)nitrosamine on urinary bladder carcinogenesis in mutant ODS rats lacking L-ascorbic acid synthesizing ability. AB - With a daily intake of 250 ppm total ascorbic acid, ODS and F344 male rats were given 0.0125%, 0.025% or 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 12 weeks, and additional groups received 0.05% BBN for 2, 4 or 8 weeks. The experiment was terminated after a total of 36 weeks. A greater response to urinary bladder carcinogenesis was observed in both strains with increasing dose of BBN or longer treatment period. However, the magnitude of urinary bladder carcinogenesis in ODS rats given the higher BBN concentrations and/or long periods of BBN treatment was less than in comparably treated F344 rats, but not with lower concentrations of BBN and/or shorter periods of BBN treatment. PMID- 2306708 TI - Carcinogenicity studies with deltamethrin in mice and rats. AB - The pesticide Deltamethrin, a synthetic pyrethroid, was studied for carcinogenicity in long-term experiments in mice and rats. Mice were given Deltamethrin by gavage in arachis oil at 0, 1, 4 or 8 mg/kg body wt for 2 years. A group of untreated controls was also available. Rats received 0, 3 or 6 mg/kg body wt. Deltamethrin in arachis oil for 2 years. In mice, an increased incidence of lymphomas was observed in the groups receiving 1 and 4 mg/kg body wt., but not in the group treated with 8 mg/kg body wt. Deltamethrin. In rats, an increased incidence of thyroid tumours was noted, but, no clear dose-response relationship was shown. Deltamethrin does not appear to be carcinogenic in mice or rats, but further studies are needed on the group of compounds to which this substance belongs. PMID- 2306709 TI - Identification of a proteolytic activity which responds to anticarcinogenic protease inhibitors in C3H-10T1/2 cells. AB - Untransformed and malignantly-transformed mouse embryo fibroblasts were found to contain an enzymatic activity which hydrolysed the synthetic substrate, Suc-Ala Ala-Pro-Phe-AMC. This activity, of approximate molecular weight 55,000, which has been partially purified by ion-exchange and gel-filtration chromatography, was maximally active at neutral pH, associated with subcellular organelles or membranes and inhibited by EDTA, EGTA, phosphoramidon and 1,10 phenanthroline, but not by PMSF or pepstatin, indicating that it may be a metalloprotease. Several other protease inhibitors, such as chymostatin, TPCK and the BBI from soybean, were also potent inhibitors of the activity; these same inhibitors are known to suppress the malignant transformation of mouse embryo fibroblast cells in vitro induced by X-irradiation or chemical carcinogens. In contrast, SBTI and pepstatin, which did not inhibit this activity, also do not suppress malignant transformation. These results suggest that this enzyme may be involved in attainment of the transformed state. PMID- 2306710 TI - Enhancing effect of oxymetholone, an anabolic steroid, on development of liver cell foci in rats initiated with N-diethylnitrosamine. AB - The promoting potential of oxymetholone (OXM) administration on development of liver cell foci was investigated in male F344 rats previously treated with N diethylnitrosamine (DEN). One week after a single injection of DEN (100 mg/kg, i.p.), rats were given OXM at a dietary level of 0.2% for the first 4 weeks and then at a concentration of 0.1% for an additional 35 weeks. All rats were killed at week 40 for histopathological and immunohistopathological examination of liver tissue. The numbers and areas of both clear cell and glutathione S-transferase placental form (GST-P) positive foci were significantly increased in the group treated with DEN and OXM as compared with the respective values for the DEN alone group. The results thus suggested that OXM possesses promoting potential for rat liver carcinogenesis. PMID- 2306711 TI - Enhanced in vitro cytotoxicity of 1,3-bis-(2-chloroethyl)-1-nitrosourea or buthionine sulfoximine combined with a reactive oxygen-generating enzyme immunotoxin. AB - The glutathione inhibitor drugs, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and buthionine sulfoximine (BSO), were tested in vitro in order to assess their cytotoxic effectiveness when combined with an enzyme immunotoxin (eIT) composed of a T-cell reactive monoclonal antibody (mAb) 097 coupled to the reactive oxygen generating enzyme, glucose oxidase (GO) (EC 1.1.3.4). As targets of this eIT we used mature human T-cells or leukemia cells that expressed the 097 epitope. We found that treatment of the cells with subtoxic amounts of mixtures of both a drug and the 097 eIT markedly potentiated cytotoxicity compared to either drug or eIT alone. PMID- 2306712 TI - Chemopreventive action of garlic on methylcholanthrene-induced carcinogenesis in the uterine cervix of mice. AB - The present paper reports the chemopreventive action of garlic on 3 methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of virgin young adult Swiss albino mice. Insertion of sterile cotton thread impregnated with beeswax containing approximately 600 micrograms of MCA inside the canal of uterine cervix results in the appearance of precancerous and cancerous lesions in the cervical epithelium. In this experimental cervical carcinogenesis model system, if garlic was administered orally at the dose level of 400 mg/kg body wt./day for 2 weeks before and 4 weeks following carcinogen thread insertion. The cervical carcinoma incidence, as compared with that of the positive control (73%), was 23%. This decline in the incidence of carcinoma was highly significant (P less than 0.01). Hyperplastic and dysplastic changes did not show any definite correlation with the garlic treatment. PMID- 2306714 TI - Clonal chromosomal changes in chronic lymphocytic leukemia. AB - Cytogenetic analysis was carried out in 28 B-CLL patients (21 males and 7 females, 38-85 years old, with median age 64 years, disease stage O-IV). Peripheral nominator cells (1 x 10(7)) or isolated B-lymphocytes were incubated in vitro for 5-7 days. The cells were stimulated by pokeweed mitogen (PWM), or phorbol myristate-acetate (PMA), with or without 10% conditioned medium (CM) derived from a T cell leukemia line or 10% B-cell growth factor (BCGF). Twenty two patients (79%) responded to PWM + CM; 5 out of 5 patients responded to PWM + BCGF. The average mitotic index (+/- S.E.M.) for PWM, PMA, PWM + CM, PMA + CM, PWM + BCGF were 0.13 +/- 0.01, 0.24 +/- 0.13, 0.51 +/- 0.11, 0.14 +/- 0.06 and 0.63 +/- 0.15, respectively. Cytogenetic analysis revealed the presence of abnormal karyotypes in 22 patients. Fourteen patients (50%) had clonal chromosome aberrations which included: monosomy 1, 9, 17, 18, 21, and X chromosome, and trisomy of chromosomes 7, 9, 20, 21 and 22. The clonal structural aberrations were i(6q), inv(12) (q15q24), del(5) (p13p15), del(10) (q24). No homogeneously staining regions (HSR) were observed. Four patients with resistance to anti neoplastic drugs showed the presence of double minute chromosomes (dmin) ranging in frequency from 5 to 50%. PMID- 2306715 TI - A new decade. PMID- 2306713 TI - Carcinogenicity tests of fecapentaene-12 in mice and rats. AB - Fecapentaenes, a class of direct-acting bacterial mutagens, have been isolated from the feces and intestinal tract of humans on a Western meat-containing diet. Two bioassays to test pure fecapentaene-12 (FP-12) for carcinogenicity were performed. FP-12 in dimethylsulfoxide (DMSO) solution was injected i.p. into newborn ICR/MA mice on days 1, 3, 7, 10, 14 and 21. The mice killed after 21 months had neoplasms in liver, lung, glandular stomach and subcutaneous fibrosarcoma. Intrarectal (i.r.) infusion of FP-12 in an aqueous vehicle into male F344 rats for 71 weeks, and killing the rats after 21 weeks more, displayed no evidence of neoplasia associated with FP-12 exposure. The positive control, N nitrosomethylurea (NMU), given i.r. as 4 2-mg doses in 2 weeks, as expected, yielded multiple colonic neoplasms in less than 11 months. Fecapentaene may exert its effect in bacteria and in newborn mice through the generation of hydroxy radicals. However, adult rodent and human colon may have adequate biochemical defense mechanisms against low level, even continuous exposures to chemicals like FP-12, and thus be at low risk of neoplasia, as was found. PMID- 2306716 TI - Lasting impressions. A psychosocial support program for adolescents with cancer and their parents. AB - Adolescents with cancer undergo numerous stresses due to their disease, its treatment, and its potential late effects. These patients may experience delayed mastery of developmental tasks, intimacy, and independence and may have long-term psychological sequelae. Parents of adolescents with cancer also encounter many stresses related to coping with their child's illness. Lasting Impressions, a support program for adolescent cancer patients and their parents, was developed to help overcome these problems. The purpose of the program is to promote positive mental health and adaptation in participants. This article describes the program's goals and methods for accomplishing them, including components and therapeutic activities. The activities include a scrapbook, a newsletter, peer visitation, and a speakers' bureau. The most recent project is a video that is shown to newly diagnosed cancer patients. This program could be easily replicated by other oncology nurses who work with adolescents or young adults with cancer. PMID- 2306717 TI - Nurses' knowledge of opioid analgesic drugs and psychological dependence. AB - Inadequate knowledge of opioid analgesic drugs and the incidence of psychological dependence are major barriers to nursing management of patients in pain. This study analyzed data obtained from 27 workshops on pain across 14 states (2,459 nurses) to determine current nursing knowledge of pharmacological management of pain. Results indicate that nurses lack knowledge in classification of opioids ranging from 23 to 98% correct response across seven analgesic drugs. Less than 25% of nurses correctly identified the frequency of psychological dependence. Further analysis revealed significant differences in basic versus advanced learners and geographical differences in knowledge. Implications are made for nursing education and practice. PMID- 2306718 TI - Attitudes to increased involvement of relatives in the care of cancer patients. Evaluation of an activation program. AB - The present study explored whether an "activation program" for relatives of cancer patients increases the frequency and duration of the relatives' visits at the hospital. It also explored the willingness of relatives to participate in patient care at the hospital and at home. Similarly, the patients' willingness to contribute to this process was examined. Relatives offered an activation program were compared by interview with relatives subjected to a routine program. Interviews were repeated at intervals of 3-4 weeks. The attitude of 67 relatives (31 in the activation group and 36 in the comparison group) were examined twice during the patient's treatment period. Of these relatives, a subgroup of 42 (22 in the activation group and 20 in the comparison group) experienced the death of the patient during the study period. At the time of the last interview, there was a difference between the groups in relatives' willingness to care for the patient at home. Contrary to expectations, more of the relatives (of all patients receiving treatment as well as the subgroup of patients who died) in the activation group were "completely unwilling" to care for the patient at home (p less than 0.05 and p less than 0.01, respectively). PMID- 2306719 TI - A modified cancer education program. Effect on cancer knowledge and beliefs of the elderly. AB - This pilot study examines the effect of a cancer education program on the knowledge and beliefs of elderly adults. The program, developed for this age group, was based on principles of adult education and on an understanding of changes related to aging. It focused on cancer risks and early diagnosis of cancer for older adults. The sample included 21 elderly adults from three retirement centers. The questionnaire used to determine knowledge and beliefs about cancer included seven scales based on the Health Beliefs Model: knowledge, severity, susceptibility, utility, barriers, behavioral intentions, and cues to action. A week following administration of the questionnaire, a program was presented: the modified cancer education program, a conventional cancer education program, or a program not related to cancer. The questionnaire was then readministered as a posttest. Findings were insignificant except that the group receiving the modified cancer program had increased scores on the knowledge scale from pretest to posttest; and the level of education accounted for 25% of the variability of posttest utility scores. The pilot study was useful for identifying problems with the questionnaire, the testing procedure, and the educational program that need to be corrected before a larger study can be undertaken. PMID- 2306720 TI - Isolation of a complementary DNA encoding the catalytic subunit of protein kinase A and studies on the expression of this sequence in rat hepatomas and regenerating liver. AB - A complementary DNA (cDNA) clone (B4) encoding the catalytic subunit of a cAMP dependent protein kinase (PKAc) was isolated from a lambda gt10 rat brain cDNA library, using a synthetic oligonucleotide probe whose sequence was based on the known amino acid sequence of a bovine cardiac PKAc. Sequence analysis of this clone revealed a region of 1002 nucleotides which encodes a protein that is 92% homologous to amino acids 17-350 of the bovine cardiac PKAc protein. This clone lacks coding sequences for amino acids 1-16 of the latter protein. Nevertheless, it provided a useful probe to analyze expression of the related gene in a variety of systems. Northern blot analyses using a 32P-labeled probe prepared from a 0.6 kilobase PstI fragment of clone B4 revealed an abundant 4.6-kilobase band in rat brain RNA and lesser amounts of this 4.6-kilobase RNA in rat heart and liver. A 4.6-kilobase RNA was also detected in RNA samples obtained from mouse fibroblasts. This probe also detected homologous RNA in a variety of nonrodent species. In subsequent experiments, this cDNA was used as a probe to elucidate the role of PKAc in post-surgical hepatic regeneration and diethylnitrosamine induced hepatomas in the rat. These experiments revealed that, following partial hepatectomy, PKAc mRNA is decreased 3-fold by 12 h, returning to normal by 72 h; hepatomas showed no consistent pattern of change in PKAc mRNA levels as compared to controls. Our results indicate that this cDNA encodes an isoform of PKAc which is distinct from PKAc-alpha isolated by Uhler et al. (Proc. Natl. Acad. Sci. USA, 83: 1300-1304, 1986) but highly homologous to PKAc-beta isolated by Showers and Maurer (J. Biol. Chem., 261: 16288-16291, 1986), that depression of cAMP dependent protein phosphorylation may be an important mechanism in the regeneration of mature rat liver but is not a consistent alteration in chemically induced hepatoma, and that this cDNA is useful as a probe for the study of the role of PKAc gene expression in growth control, particularly in rodent species. PMID- 2306721 TI - Assessment of tumor energy and oxygenation status by bioluminescence, nuclear magnetic resonance spectroscopy, and cryospectrophotometry. AB - The energy and oxygenation status of tumors from two murine sarcoma lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) were assessed using three independent techniques. Tumor energy metabolism was investigated in vivo by 31P nuclear magnetic resonance spectroscopy. After nuclear magnetic resonance measurements, tumors were frozen in liquid nitrogen to determine the tissue ATP concentration by imaging bioluminescence and to register the intracapillary oxyhemoglobin (HbO2) saturation using the cryospectrophotometric method. There was a positive correlation between the nucleoside triphosphate beta/total resonance ratio or a negative correlation between the Pi/total resonance ratio and the model ATP concentration obtained by bioluminescence, respectively. This was true for small tumors with no extended necrosis irrespective of tumor type. Moreover, a positive correlation was obtained between the HbO2 saturations and the ATP concentration measured with bioluminescence. The results demonstrate the potential of combined studies using noninvasive, integrating methods and high-resolution imaging techniques for characterizing the metabolic milieu in tumors. PMID- 2306722 TI - Generation of human lymphokine-activated killer cells following brief exposure to high dose interleukin 2. AB - Current laboratory lymphokine-activated killer (LAK) cell activation procedures require culture of peripheral blood mononuclear cells (PBMC) in the presence of 1000-1500 units/ml of interleukin 2 (IL-2) for 3-7 days. However, we have observed that a brief exposure (15 min-1 h) of PBMC to a high concentration of IL 2 results in the maturation of LAK precursor cells to cytolytic effector cells over the course of 1-3 days. These IL-2-pulsed LAK cells express cytolytic activity comparable to that of nonpulsed PBMC (cultured continuously in IL-2) at 3 days of culture. The acquisition of cytolytic activity followed the same kinetics for both pulsed and nonpulsed mononuclear cells and was maintained when tested at day 7. The pulsed LAK cells were capable of significantly lysing 11 different tumor targets tested and flow cytometric analysis revealed that pulsed LAK cells were phenotypically similar to nonpulsed LAK cells. Serum obtained from cancer patients undergoing IL-2/LAK cell therapy did not inhibit the maturation of the pulsed mononuclear cells into LAK cells. Interestingly, only PBMC obtained from cancer patients receiving in vivo IL-2 infusions could be induced to generate the same levels of cytolytic activity as those in nonpulsed cells using this pulse procedure. PBMC obtained from healthy, normal donors could not be pulsed to the same levels of activation as nonpulsed LAK cultures. Our study demonstrates that for the generation of maximum LAK cell cytolytic activity, LAK cell precursors must be primed in vivo with IL-2. Implementation of this procedure could eliminate the high cost of cell culture which normally accompanies IL-2/LAK cell therapy. Such an approach could make IL-2/LAK cell therapy more accessible for cancer patients. PMID- 2306723 TI - Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer. AB - Adriamycin (ADR), an anthracycline anticancer drug, was bound to the poly(aspartic acid) chain of poly(ethylene glycol)-poly(aspartic acid) block copolymer by amide bond formation between an amino group of Adriamycin and the carboxyl groups of the poly(aspartic acid) chain. The polymeric drug thus obtained was observed to form a micelle structure possessing diameter of approximately 50 nm, with a narrow distribution, in phosphate-buffered saline and to show excellent water solubility despite a large amount of ADR introduction. Further, it was able to be stored in lyophilized form without losing its water solubility in the redissolving procedure. Increased stability of the bound Adriamycin molecules in phosphate-buffered saline and elimination of binding affinity for bovine serum albumin due to the micelle formation were further advantages of this polymeric drug. In vivo high anticancer activity of this micelle-forming polymeric drug against P 388 mouse leukemia was obtained with less body weight loss than that seen with free ADR, due to low toxicity as compared with free ADR. PMID- 2306724 TI - Characteristics of a novel transport system for folate compounds in wild-type and methotrexate-resistant L1210 cells. AB - The growth requirements and transport characteristics of folate compounds in a methotrexate-resistant L1210/R81 cell line were compared with parental cells. Concentrations for half-maximal growth of the resistant cells with folate (350 nM) and 5-formyltetrahydrofolate (20 nM) were found to be higher by 2.7-fold and 20-fold, respectively, relative to the parent, suggesting that changes had occurred in the transport of these folate compounds. Transport measurements revealed that the resistant cells have lost the capacity to transport methotrexate and other folate compounds via the reduced-folate transport system but that a second previously undescribed transport system is present. Uptake of folate via this second route is energy dependent, exhibits saturation kinetics, can be inhibited by substrate analogues, and is activated by a reduction in pH. The pH effect is substantial since uptake at 5.0 microM folate can be increased 10-fold by decreasing the pH from 7.4 to 6.2. The observed Kt for half-maximal influx of folate at pH 6.8 was 5.2 microM, and the Vmax was 0.55 pmol/min/mg of protein. Ki values for methotrexate, 5-methyltetrahydrofolate, and 5 formyltetrahydrofolate were 10.2, 3.2, and 2.7 microM, respectively. Transport activity was not affected by depleting internal stores of folate by growth in folate-free medium, and this same transport system was also present in comparable amounts in wild-type cells. In the latter case, interfering uptake via the reduced-folate transport system was blocked by bromosulfophthalein and thiamine pyrophosphate. Methotrexate and 5-formyltetrahydrofolate were also transported via this alternative, pH-dependent route, whereas little or no uptake of 5 methyltetrahydrofolate could be detected. The results indicate that antifolate resistance in L1210/R81 cells was induced by inactivating the reduced-folate transport system and by utilizating a secondary route which has a low capacity for transporting methotrexate but whose activity is sufficient to permit cell growth in medium supplemented with folate or 5-formyltetrahydrofolate. PMID- 2306725 TI - Metabolism and pharmacokinetics of the camptothecin analogue CPT-11 in the mouse. AB - A new water-soluble derivative of camptothecin, 7-ethyl-10-[4-(1-piperidino)-1 piperidino]carbonyloxycamptothecin (CPT-11), did not exhibit potent antitumor activity in vitro against experimental tumor cells. The 50% effective doses of CPT-11 against KB and L1210 cells were 1100 and 5500 ng/ml, respectively. These values were markedly higher than those of camptothecin (CPT, 0.98 and 3.7 ng/ml) or 7-ethyl-10-hydroxycamptothecin (SN-38, 0.37 and 3.6 ng/ml). CPT-11 was found to be converted into SN-38 in mouse serum. In vitro incubation of CPT-11 in mouse serum or tissue homogenate enhanced the growth-inhibitory activity much more than that expected from the concentration of CPT-11. This enhancement of the activity coincided with that expected from the SN-38 concentration in incubated serum or homogenate, though the contribution of CPT-11 could not be refuted. SN-38 is considered to play a major role in the antitumor activity when CPT-11 is incubated in serum or homogenate. The plasma CPT-11 concentration decreased biexponentially after i.v. administration of CPT-11 into mice with a biological half-life of 0.8 to 1.1 h. The area under the plasma CPT-11 concentration-time curve showed dose dependency. The SN-38 concentration decreased for the first 30 min after administration and was then maintained for a few hours at about 0.1 microgram/ml after i.v. administration of 20 and 40 mg/kg of CPT-11 followed by the log-linear terminal phase with a half-life of about 2 h which was independent of the dose. It is suggested that the maintenance of plasma SN-38 concentration might be necessary for it to exhibit antitumor activity in vivo. PMID- 2306726 TI - Nonlinear pharmacokinetics of CPT-11 in rats. AB - The pharmacokinetics of a new water-soluble derivative of camptothecin. 7-ethyl 10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), and its major metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), was investigated after i.v. administration of 1 to 40 mg/kg of CPT-11 to rats. The plasma concentration of CPT-11 decreased biexponentially. The area under the concentration-time curve increased nonlinearly as the dose increased. SN-38 was found in the plasma, bile, urine, and feces. The SN-38 level was maintained at 0.06 to 0.08 micrograms/ml for 0.5 to 5.5 h depending on the dose, followed by exponential decay. Thirty three to 58% of the CPT-11 was excreted without metabolism into the bile and urine for 24 h. SN-38 was mainly excreted into the bile. Analysis of the clearance has shown nonlinear pharmacokinetics which was due to metabolic processes such as the conversion of CPT-11 to SN-38. PMID- 2306727 TI - Biochemical and growth inhibition studies of methotrexate and aminopterin analogues containing a tetrazole ring in place of the gamma-carboxyl group. AB - The biological activities of novel analogues of methotrexate (MTX) and aminopterin (AMT) in which the gamma-carboxyl was replaced by a 1H-tetrazol-5-yl ring, an isosteric group with acidic properties similar to a carboxyl group, were investigated. The tetrazolyl analogues of MTX and AMT were more potent inhibitors of the growth of CCRF-CEM and K562 human leukemia cell lines during continuous (120 h) and 24-h pulse exposure than were the respective parent drugs; only when the exposure time was reduced to 6 h were the parent drugs more potent. These inhibitory effects on growth correlated with the onset of and recovery from inhibition of de novo thymidylate biosynthesis. Growth inhibition by the analogues was protectable by leucovorin. MTX-resistant CCRF-CEM sublines with decreased transport or increased dihydrofolate reductase (DHFR) levels were cross resistant to the analogues. The analogues were as potent as their parent drugs in inhibiting DHFR activity in vitro and at displacing [3H]MTX from intracellular DHFR. Each analogue was more effective than its parent drug at inhibiting uptake of [3H]MTX into CCRF-CEM cells. The tetrazole analogue of AMT was a linear competitive inhibitor (Kis = 50 microM) of CCRF-CEM folylpolyglutamate synthetase, while the tetrazole analogue of MTX, unlike all other inhibitors, was linear noncompetitive (Kis = 51 microM, Kii = 321 microM). The data suggest that, compared with MTX or AMT, the tetrazole substituent, in place of the gamma carboxyl group, allows more efficient transport into cells via the reduced folate/MTX carrier and the resulting greater uptake of the analogues leads to inhibition of DNA synthesis and cell death at lower extracellular concentrations during long exposures. The mechanism of cell death could involve inhibition at folypolyglutamate synthetase, but DHFR is the primary target. The low potency of the analogues during short exposure is presumably related to the inability to form the poly-gamma-glutamyl metabolites required for intracellular retention. PMID- 2306728 TI - Homozygous deficiency at autosomal locus aprt in human somatic cells in vivo induced by two different mechanisms. AB - Associations between germinal and somatic mutations at autosomal loci play an important role in the development of some tumors, including retinoblastoma. In an attempt to determine whether equivalent events occur in vivo at other loci, we cloned and enumerated somatic T-cells with mutations at the aprt locus, by taking advantage of both the presence of a human disease caused by genetic defects at this locus and an effective selection procedure for the deficient mutants. T cells homozygously deficient at this locus (aprt-/-) were found in all four heterozygotes (aprt+/-) studied, at an average frequency of 1.3 x 10(-4). From 310 normal individuals, we identified only one aprt-/- clone, and the calculated frequency of aprt-/- T-cells in aprt+/+ individuals was 5.0 x 10(-9). These results confirm that a two-step process (aprt(+/+)----aprt(+/-)----aprt-/-) is functional through two different mechanisms (germinal-somatic and somatic somatic) in vivo. Our data suggest that the two-step mutations leading to homozygous deficiencies at the somatic cell level, as proposed for the carcinogenic mechanisms for retinoblastomas and other human tumors, generally occur at rather high frequencies at various autosomal loci in humans. PMID- 2306729 TI - Effect of a calcium-enriched diet on the colonic epithelial hyperproliferation induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats on a low calcium and fat diet. AB - We examined whether hyperproliferation of colonic crypt epithelium during cancer induction by N-methyl-N-nitro-N-nitrosoguanidine (MNNG), in rats on a low fat and calcium diet could be reduced by added calcium p.o. From the age of 4 weeks, 104 male Sprague-Dawley rats received a low fat (3.5%), low calcium (0.05% calcium ion), and low vitamin D (0.4 IU/g) diet. Sixty-four also had calcium salts, derived from either calcium lactate or solubilized calcium carbonate, added to their drinking water; therefore their total calcium intake was about 1% of daily diet. At age 12 weeks the rats were divided into 4 treatment groups: 8 rats, not receiving added calcium, had rectal saline instillations weekly (saline control group) and were sacrificed after a further 28 weeks; 3 groups of 32 rats each received intrarectal MNNG (1.5 mg) weekly. One group, not receiving added calcium, was the MNNG control group; while the second group also received added calcium lactate, and the third group received calcium carbonate. Groups of 24 were sacrificed periodically until 28 weeks of treatment. Rats were sacrificed and epithelial proliferation was estimated, 1 week after the last intrarectal instillation, by in vivo labeling with tritiated thymidine and measuring the ratio of labeled to total colonic crypt epithelial cells. The mean labeling index of the MNNG treated and added calcium groups were significantly higher (8.7-9.5%) than that of the saline controls (2.8%) only at week 28; however, it was then still significantly less than that of the MNNG controls not having added calcium (17.9%). Hyperproliferation, during induction of colonic cancer by MNNG in rats on a low calcium diet, can be reduced by a calcium enriched diet even in the presence of a low fat intake. PMID- 2306730 TI - Inhibition of DNA excision repair by methotrexate in Chinese hamster ovary cells following exposure to ultraviolet irradiation or ethylmethanesulfonate. AB - Previous results have suggested that methotrexate (MTX) could interfere with the repair of spontaneous DNA damage. To determine its effects on induced DNA damage, MTX was compared to hydroxyurea and arabinofuranosylcytosine (H/A), a drug combination known to block the DNA polymerase step of excision repair, for its ability to cause the accumulation of single-strand breaks (SSB) following exposure to either UV light or the alkylating agent ethylmethanesulfonate in Chinese hamster ovary cells. SSB were measured by alkaline elution 1, 2, and 6 h after exposure to either 1.8 mg/ml of ethylmethanesulfonate or 10 J/m2 of UV in cells pretreated with MTX or H/A. Following exposure to ethylmethanesulfonate, significant accumulation of SSB occurred in cells pretreated with either H/A or MTX. Coadministration of hypoxanthine and thymidine in MTX-treated cells prevented SSB accumulation, indicating that nucleotide depletion by MTX had inhibited repair synthesis. After UV irradiation, SSB accumulation was much less in MTX- than in H/A-treated cells. MTX was found to have no effect on the incision of UV damage. These results indicate that nucleotide depletion by MTX can affect the repair of DNA damage by exogenous agents, and that the extent of inhibition is dependent on the type of damage induced. PMID- 2306731 TI - Antitumor activity of L/1C2-4-desacetylvinblastine-3-carboxhydrazide immunoconjugate in xenografts. AB - The murine IgG3 monoclonal antibody L/1C2 is reactive with a high percentage of human carcinomas and has preferentially strong reactivity with tumors of squamous differentiation. This antibody was tested for antitumor activity in vitro and in xenograft models as a carbohydrate-linked immunoconjugate with the Vinca derivative 4-desacetylvinblastine-3-carboxhydrazide (DAVLBHYD). The conjugate retained good immunoreactivity and was highly active in a cytotoxicity assay. In human tumor nude mouse xenograft studies, L/1C2-DAVLBHYD antitumor activity was superior to that seen with free drug, free antibody, mixtures of free drug and free antibody, or control DAVLBHYD conjugates prepared with non-tumor-binding IgGs. With well-established tumors, potent antitumor activity was observed, including the ability to specifically regress greater than 400-mg tumors to 0 mg. In some cases, apparent long-term cures were effected. In studies using six different human tumor xenografts, the level of potency of L/1C2-DAVLBHYD was related to L/1C2 antigen expression, although the growth rate probably also contributes to the conjugate sensitivity of the tumors. PMID- 2306732 TI - Oxidation and DNA binding of (+)-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene in mouse epidermis in vivo and effects of coadministration of catechol. AB - Using a stereochemical probe as described by Marnett (Carcinogenesis (Lond.), 8: 1365-1373, 1987), we have investigated the mechanism of oxidation of (+)-[3H]BaP 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene [(+)-[3H]BaP-7,8-diol] in mouse epidermis in vivo. Groups of mice were topically treated with (+)-[3H]BaP-7,8-diol (60 nmol/mouse) and sacrificed at intervals from 1/2 to 8 h post treatment. (-)-Anti- and (+)-syn-7,8-[3H]dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) were formed as metabolites in a ratio of about 4 to 1, respectively, as determined by HPLC analysis of the hydrolysis products. Pretreatment of mice with indomethacin, an inhibitor of prostaglandin H synthase, did not alter the ratio of anti- to syn-BPDE-derived hydrolysis products. Pretreatment of mice with the cytochrome P-450 inducer, beta-naphthoflavone, yielded twice the level of syn [3H]BPDE in mouse skin at the 1/2-h survival point. However, this enhancing effect diminished over time. Coadministration of 1,2-dihydroxybenzene (catechol) with (+)-[3H]BaP-7,8-diol decreased the formation of (-)-anti-[3H]BPDE and also decreased lipid peroxidation, as measured by the extent of formation of thiobarbituric acid-reactive material in mouse epidermis. Analysis of mouse epidermal DNA adducts 24 h after topical application (+)-[3H]BaP-7,8-diol indicated that the major adduct is not formed from the major metabolite (-)-anti BPDE. Acid hydrolysis of the major adduct resulted in the formation of a small amount of r-7,c-9,c-10,t-8-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene and two unidentified products different from 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydro BaP. Coadministered catechol suppressed the formation of this adduct by 30%. The present observation suggests that a peroxyl radical-mediated epoxidation pathway is involved in the oxidation of (+)-[3H]BaP-7,8-diol in mouse skin in vivo. PMID- 2306733 TI - Detection of pS2 messenger RNA in gynecological cancers. AB - Estrogen-inducible pS2 mRNA was previously detected in human cancer cell lines the growth of which was sensitive to estrogen. In the present study, the expression of the pS2 gene was analyzed in 111 gynecological carcinomas. The pS2 message was detected in greatest abundance in 6 primary carcinomas of the ovary (6 of 29), 4 of these being mucinous cystadenocarcinomas. A secondary carcinoma of the ovary, and another of the omentum (1 of 4), also contained detectable levels of pS2 mRNA. Weak pS2 mRNA signals were occasionally observed in endometrial (2 of 55) and cervical carcinomas (2 of 33) as well. There was a poor correlation between estrogen receptor and pS2 mRNA in ovarian carcinomas. PMID- 2306734 TI - Metabolism and DNA single strand breaks induced by 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone and its analogues in primary culture of rat hepatocytes. AB - Previous studies have shown that the tobacco specific nitrosamine, 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is hepatocarcinogenic and results in alkylation of hepatic DNA in F344 rats. In this study, we have characterized the metabolism of NNK in cultured rat hepatocytes and have established the relationship between various metabolic pathways and the induction of DNA single strand breaks. DNA fragmentation by NNK and two other related N nitrosamines, N'-nitrosonornicotine and nitrosodimethylamine, were compared. Metabolism of [5-3H]NNK (4.5 microM) by carbonyl reduction, alpha-carbon hydroxylation, and pyridine N-oxidation was linear from 0 to 6 h and with 0 to 2 x 10(6) hepatocytes. Using the alkaline elution assay, we observed that NNK induces DNA single strand breaks (SSB) in a dose (1-10 mM) and time (0.5-6 h) dependent manner. SSB induced by NNK (5 mM; rate of elution between 3 and 9 h, 0.117) are rejoined partially within 2 h (rate, 0.039) and totally 12 h after exposure. NNK N-oxide (5 mM) produces a smaller number of SSB (rate, 0.017) than NNK (rate, 0.105) suggesting that pyridine N-oxidation of NNK is a deactivation pathway. Hydrolysis of carbethoxy-nitrosaminomethane and 4-(N-carbethoxy-N nitrosamino)-1-(3-pyridyl)butanone yields methyldiazohydroxide and 4-(3-pyridyl) 4-oxobutyl-diazohydroxide, respectively. These two alkylating intermediates are generated during alpha-carbon hydroxylation of NNK. After treatment of hepatocytes with 5 microM carbethoxynitrosaminomethane and 1 mM 4-(N-carbethoxyl N-nitrosamino)-1-(3-pyridyl)butanone, the rates of DNA elution were 0.092 and 0.120, respectively. Carbonyl reduction of NNK leads to 4-(methylnitrosamino)-1 (3-pyridyl)butan-1-ol (NNAl). Reaction of NNK with methyl magnesium iodide gives 1-MeNNAl with 82% yield, NNAl but not 1-MeNNAl can be reoxidized to NNK. Both 5 mM NNAl (rate, 0.073) and 5 mM 1-MeNNAl (rate, 0.054) induce SSB indicating that NNAl does not require reconversion to NNK to be activated to DNA damaging intermediates. alpha-Methylene hydroxylation of NNK results in an equimolar formation of methyldiazohydroxide and 4-oxo-4-(3-pyridyl)-butanal. This aldehyde, at a concentration of 1 mM, induces the same frequency of SSB (rate, 0.116) as 5 mM NNK (0.105) and could possibly play a role in the carcinogenicity of NNK.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2306735 TI - Transport and metabolism of 9-beta-D-arabinofuranosylguanine in a human T lymphoblastoid cell line: nitrobenzylthioinosine-sensitive and -insensitive influx. AB - Nitrobenzylthioinosine (NBMPR), dipyridamole, and dilazep, potent inhibitors of nucleoside transport, were found to be ineffective in preventing 9-beta-D arabinofuranosylguanine (ara-G)-induced inhibition of MOLT 4 and CCRF CEM cell growth, ara-G (2.0 microM) was metabolized to 9-beta-D-arabinofuranosylguanine 5' triphosphate in MOLT 4 cells, and the levels of this metabolite were not affected by the presence of 5.0 microM NBMPR in the incubation medium. Permeation of the MOLT 4 cell membrane by ara-G occurred primarily by means of the NBMPR-sensitive nucleoside transport system. However, a residual transport component accounting for 10-20% of the total transport activity was demonstrated in the presence of NBMPR. This component was inhibited by adenine and hypoxanthine but not by dilazep, dipyridamole, or other nucleosides. In contrast, inhibitors of nucleoside transport readily reversed the cytotoxic effect of 7-deazaadenosine (tubercidin) in both MOLT 4 and CCRF CEM cells. The levels of tubercidin 5' triphosphate formed from 2.0 microM tubercidin in MOLT 4 cells were reduced by 80% in the presence of 5.0 microM NBMPR. The influx of tubercidin into MOLT 4 cells was found to occur primarily by means of the NBMPR-sensitive nucleoside transport system. This same system mediated the transport of ara-G into human erythrocytes. PMID- 2306736 TI - Role of asialo-GM1 positive liver cells from athymic nude or polyinosinic polycytidylic acid-treated mice in suppressing colon-derived experimental hepatic metastasis. AB - Liver-derived (LD) murine colon adenocarcinoma MCA-38 cells injected into the ileocolic vein (ICV) of C57BL/6 mice developed distinct hepatic foci within 14-21 days and survived for an average of 19-35 days. In contrast, C57BL/6-nu/nu mice given injections of LD-MCA cells by the same route did not develop hepatic lesions. Furthermore, 111In-labeled LD-MCA-38 tumor cells were rapidly taken up by the liver of conventional mice within 1 h and 73% of the radioactivity remained after 24 h. However, about 60% of the 111In-labeled LD-MCA-38 tumor cells were cleared from the liver of nude mice after 24 h. Nonparenchymal liver cells isolated from untreated conventional mice displayed little cytotoxicity against freshly excised 51Cr-labeled LD-MCA-38 cells but did lyse the standard natural killer target, YAC-1 tumor cells, in 4 h chromium release assays. On the other hand, nonparenchymal liver cells but not spleen cells from nude mice were cytotoxic to 51CR-labeled LD-MCA-38 in vitro. The nonparenchymal liver cell population responsible for tumor killing was phenotypically nonadherent and asialo-GM1 (AsGM1) positive. C57BL/6 mice treated with polyinosinic-polycytidylic acid [poly(IC)] also displayed cytotoxic activity against LD-MCA-38 tumor cells in vitro. Furthermore, poly(IC) treatment of mice 1-8 days after tumor inoculation suppressed the number of hepatic foci and also significantly increased the life span of tumor-bearing mice. Treatment of athymic nude mice or poly(IC)-treated conventional mice with anti-AsGM1 induced significant numbers of foci and significantly decreased the life span of MCA-38-bearing mice suggesting that AsGM1-positive cells in the liver of these mice may inhibit tumor growth in vivo. In conclusion, the host defense system of the liver from athymic nude or poly(IC)-treated mice possess AsGM1-positive cells that can suppress tumor implantation or tumor growth in the early stages of metastasis in liver. PMID- 2306737 TI - Increased local antitumor effects of interleukin 2 liposomes in mice with MCA-106 sarcoma pulmonary metastases. AB - The effects of liposome formulations of interleukin 2 (IL-2) and local route were studied in C57BL/6 mice with MCA-106 sarcoma pulmonary metastases. IL-2 liposomes made by hydration of powdered dimyristoyl-phosphatidylcholine with aqueous recombinant IL-2 had 95% of the IL-2 associated with the lipid fraction. When mice with pulmonary micrometastases were treated once daily with free cytokine on days 5, 6, and 7 after tumor inoculation, the intrathoracic route was superior to the i.p. or s.c. routes. When IL-2 liposomes were administered by the local intrathoracic route, significantly better antitumor effects (P less than 0.01) were seen compared to empty liposomes or free IL-2 as determined by (a) increased survival and (b) reduced numbers of pulmonary metastases. Minimal toxicity was observed. Results indicate that local route and incorporation of IL-2 in liposomes may enhance therapeutic efficacy and facilitate more practical daily dosing regimens. PMID- 2306738 TI - Increased removal of DNA-bound platinum in a human ovarian cancer cell line resistant to cis-diamminedichloroplatinum(II). AB - A human ovarian cancer cell line resistant to cis-diamminedichloroplatinum(II) (DDP) (2780CP) was compared with its DDP-sensitive parental cell line (A2780) to determine whether differences in the removal rate of DNA-bound platinum were related to resistance. Both cell lines were treated in vitro with various doses of DDP for 2 h and subsequently incubated in arginine-deficient Eagle's minimum essential medium with 2.5% dialyzed fetal bovine serum in the presence or absence of aphidicolin. After 0, 12, and 24 h, DNA was isolated from the cells and DNA bound platinum was determined by flameless atomic absorption spectrophotometry. Binding of platinum to DNA of either cell line was a linear function of concentration ranging from 20 to 80 microM DDP. Platinum binding was almost equal at each dose in both cell lines. 2780CP cells that were 3-fold resistant to DDP lost 30.5 to 40.1% of their total DNA-bound platinum, compared with a 1.3 to 16.1% loss for A2780 cells, 12 to 24 h after a 2-h exposure to 40 microM DDP, respectively. Aphidicolin (3.0 micrograms/ml) increased the cytotoxicity in 2780CP cells by about 2-fold and caused a significant delay in the time required for platinum removal in the resistant cells (14.6 and 18.9% at 12 and 24 h). These studies indicate that the mechanism of DDP resistance in the 2780CP cell line is related to an increased ability to remove platinum-DNA adducts, and not to a difference in initial DDP binding to DNA. PMID- 2306740 TI - Marital status and the incidence of sarcomas of the uterus. AB - To explore further the descriptive epidemiology of sarcomas of the uterus, we examined the distribution of marital status among 1479 white women diagnosed as having one of these tumors between January 1, 1973, and December 31, 1986, in 7 geographically defined areas of the United States. We estimated incidence rates based on the distribution of marital status of the female population of these seven areas as of 1980; adjustment for the prevalence of intact uteri in the estimated population-at-risk was performed using data from a survey of a representative sample of the United States population in 1982-1984. The incidence of uterine sarcoma was higher among never-married compared to ever-married women (rate ratio, 1.5; 95% confidence intervals, 1.3, 1.8). The association with marital status was similar for each of the three major histological categories (leiomyosarcomas, malignant mixed mullerian tumors, and endometrial stromal sarcomas). These results provide evidence that one or more characteristics associated with a woman's marital status may play a role in the etiology of one or more histological types of uterine sarcoma. PMID- 2306739 TI - Conjugation of 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 with intracellular glutathione and enhancement of its antiproliferative activity by glutathione depletion. AB - The major dehydration product of prostaglandin D2, 9-deoxy-delta 9,delta 12(E) prostaglandin D2, is a potent cytotoxic compound. Like other cytotoxic prostaglandins, this compound possesses an alpha, beta-unsaturated ketone group to which cytotoxic activity has been attributed. This prostaglandin was found to readily conjugate with glutathione (GSH) in vitro. When 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 was incubated with Chinese hamster ovary or hepatoma tissue culture cells, it was rapidly taken up and was recovered in the cell lysate primarily as a GSH conjugate in which the keto group at C-11 and the delta 12 double bond had been reduced. Identification of the GSH conjugate was accomplished by analysis by fast atom bombardment mass spectrometry following purification by high performance liquid chromatography. This GSH conjugate and its cysteinylglycinyl and cysteinyl metabolites were also identified in the cell culture medium. 9-Deoxy-delta 9,delta 12(E)-prostaglandin D2 inhibited cell proliferation of these two cell lines in a concentration dependent manner. Depletion of intracellular glutathione by treatment with diethyl maleate and buthionine sulfoximine decreased the amount of intracellular conjugated prostaglandin recovered, and significantly enhanced the antiproliferative effect of 9-deoxy-delta 9-delta 12(E)-prostaglandin D2 on the growth of these cell lines in a concentration dependent fashion. We conclude that intracellular GSH may modulate the antiproliferative activity of 9-deoxy-delta 9,delta 12(E) prostaglandin D2 and, possibly, of other cytotoxic prostaglandins. PMID- 2306741 TI - Suppression of tumorigenicity of a human lung carcinoma line by nontumorigenic bronchial epithelial cells in somatic cell hybrids. AB - Hybrid cell lines between HuT292-DM, a human lung carcinoma line resistant to 6 thioguanine and ouabain, and either normal human bronchial epithelial cells (NHBE) or an SV40 "immortalized" but nontumorigenic derivative thereof (BEAS-2B), have been isolated by double selection. Hybrids of NHBE and HuT292-DM cells senesced after 40-43 population doublings in culture. In contrast, hybrids of BEAS-2B and HuT292-DM showed no sign of a culture "crisis" and have an indefinite life span. HuT292-DM cells produced tumors in 100% of athymic nude mice with a mean latency of 27 days, whereas tumorigenicity was totally suppressed in 76% of the BEAS-2B x HuT292-DM hybrids, with a 2- to 3-fold increased tumor latency in the remaining 24% of these hybrids. While the hybrids are hypotriploid to hypotetraploid, the parental lines are hypodiploid. The growth of HuT292-DM cells is stimulated, whereas NHBE and BEAS-2B cells are inhibited by serum. The growth response of the BEAS-2B x HuT292-DM hybrids to serum is similar to that of HuT292 DM cells. Thus, tumorigenicity and culture longevity are dominantly controlled by the nontumorigenic parent (NHBE or BEAS-2B). On the other hand, serum responsiveness is more similar to that of the tumorigenic parent (HuT292-DM). PMID- 2306742 TI - Effects of microinjected photoreactivating enzyme on thymine dimer removal and DNA repair synthesis in normal human and xeroderma pigmentosum fibroblasts. AB - UV-induced thymine dimers (10 J/m2 of UV-C) were assayed in normal human and xeroderma pigmentosum (XP) fibroblasts with a monoclonal antibody against these dimers and quantitative fluorescence microscopy. In repair-proficient cells dimer specific immunofluorescence gradually decreased with time, reaching about 25% of the initial fluorescence after 27 h. Rapid disappearance of dimers was observed in cells which had been microinjected with yeast photoreactivating enzyme prior to UV irradiation. This photoreactivation (PHR) was light dependent and (virtually) complete within 15 min of PHR illumination. In general, PHR of dimers strongly reduces UV-induced unscheduled DNA synthesis (UDS). However, when PHR was applied immediately after UV irradiation, UDS remained unchanged initially; the decrease set in only after 30 min. When PHR was performed 2 h after UV exposure, UDS dropped without delay. An explanation for this difference is preferential removal of some type(s) of nondimer lesions, e.g., (6-4) photoproducts, which is responsible for the PHR-resistant UDS immediately following UV irradiation. After the rapid removal of these photoproducts, the bulk of UDS is due to dimer repair. From the rapid effect of dimer removal by PHR on UDS it can be deduced that the excision of dimers up to the repair synthesis step takes considerably less than 30 min. Also in XP fibroblasts of various complementation groups the effect of PHR was investigated. The immunochemical dimer assay showed rapid PHR-dependent removal comparable to that in normal cells. However, the decrease of (residual) UDS due to PHR was absent (in XP-D) or much delayed (in XP-A and -E) compared to normal cells. This supports the idea that in these XP cells preferential repair of nondimer lesions does occur, but at a much lower rate. PMID- 2306743 TI - Photosensitization of human leukemic cells by anthracenedione antitumor agents. AB - 1,4-Diamino-substituted anthraquinone antitumor agents (mitoxantrone and ametantrone) and structurally related 1,5- and 1,8-diamino-substituted compounds (AM1 and AM2) were tested for their ability to photosensitize human leukemic cells in culture. Viability was measured using the 3,4,5-dimethylthiazol-2,5 diphenyl tetrazolium bromide assay, and DNA and membrane damage were assessed. Following a 1-h exposure to AM2, a dose of drug required to give 50% loss of cell viability (53 microM) was obtained in the dark, which was reduced to approximately 2.4 microM following illumination for 2 min (lambda greater than 475 nm), a dose of light that was completely nontoxic to the cells in the absence of drug. A shift in the cell viability curve was also observed for AM1 but, under identical conditions, the dose modification was only 8.9. In contrast, neither ametantrone nor mitoxantrone gave a decreased viability upon illumination. DNA single-strand breaks as measured by alkaline elution correlated with cell viability. Frank DNA single-strand breaks were produced by AM2 and light, suggesting the production of free radicals. The strand breaks produced by AM2 in the dark and by mitoxantrone (with or without illumination) were protein concealed. No evidence of photo-induced membrane damage, as determined by transport of the model amino acid cycloleucine, could be observed even at supralethal doses. PMID- 2306744 TI - Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis. AB - Neoplastic meningitis can result from leptomeningeal dissemination of a variety of cancers. We now report the development of animal models of human neoplastic meningitis and activity of intrathecal 4-hydroperoxycyclophosphamide (4-HC) against the human rhabdomyosarcoma cell line TE-671 and the human glioma cell line D-54 MG grown in the subarachnoid space of athymic rats. The injection of 5 x 10(5) TE-671 or D-54 MG cells resulted in leptomeningeal tumor growth from the base of the brain to the cauda equina. Daily weights and neurological examinations revealed progressive neurological deficits and weight loss, with death occurring between Days 21 and 27 for TE-671 and Days 14 and 26 for D-54 MG. 4-HC toxicity in non-tumor-bearing rats was assessed at dose levels of 2.0, 10.0, 15.0, and 20.0 mM, with clinical and histological evidence of neurotoxicity observed at the 2 highest dose levels. Intrathecal treatment with 4-HC on Day 8 following injection of TE-671 resulted in an increase in median survival of 20% (P = 0.04) at 1.0 mM 4-HC and 41% (P less than 0.001) at 2.5 mM 4-HC. Intrathecal treatment with 4-HC (2.5 mM) on Day 5 following injection of D-54 MG resulted in an increase in median survival of 23% (P = 0.009). These studies show the usefulness of the athymic rat model of human neoplastic meningitis and demonstrate the efficacy in vivo of intrathecally administered 4-HC against a human glioma and a human rhabdomyosarcoma cell line and the lack of toxicity at therapeutic levels of 4-HC in normal athymic rats. PMID- 2306745 TI - Pathobiology of lung tumors induced in hamsters by 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone and the modulating effect of hyperoxia. AB - Neuroendocrine lung cancer is among the most common types of lung cancers in smokers. We have recently shown that exposure of hamsters to N nitrosodiethylamine and hyperoxia causes a high incidence of this tumor type. In this study, we show that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone also causes neuroendocrine lung tumors in hyperoxic hamsters. Animals maintained in ambient air while being treated with 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone developed pulmonary adenomas composed of Clara cells and alveolar type II cells. Pathogenesis experiments provide evidence for the tumors caused by 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone in ambient air being derived from Clara cells. In the hyperoxic hamsters, the neuroendocrine carcinogenesis appears to involve two stages: (a) transformation of focal alveolar type II cells into neuroendocrine cells and (b) development of neuroendocrine lung tumors from such foci. PMID- 2306746 TI - Response to a standard oral levodopa test in parkinsonian patients with and without motor fluctuations. AB - The acute dose-response profile of a standard oral levodopa dose was followed, over a maximum 8-h period, in 13 patients with and 10 patients without motor fluctuations using a battery of motor quantitative tests (tapping and walking speed, and multiple choice reaction and movement times). Thirteen age-matched normal controls performed tapping and psychomotor tests, at the same time intervals, over a 4-h period. Tapping test and movement times proved significantly impaired in all patients and were the best indicator of levodopa effect, while walking speed and reaction times were apparently of less value, except in severely affected patients. The duration of the levodopa antiparkinsonian effect differed markedly between the two groups, since fluctuating patients returned to prelevodopa dose values within 4 h (mean +/- SEM: 203 +/- 16 min), while in the stable group motor scores remained significantly higher than baseline values up to at least 7 h postdose. The magnitude of the effect was similar in the two groups, but response was complicated by mild to severe dyskinesias in 9 of 13 fluctuating subjects. The pharmacokinetic parameters of levodopa were almost identical in the two groups. Our data add further weight to the hypothesis that cerebral pharmacokinetic or pharmacodynamic factors are responsible for motor fluctuations. Oral levodopa doses coupled with objective tests of motor performance may prove a practical clinical tool to assess and optimize the relationship between drug dose and therapeutic effect. PMID- 2306747 TI - Lack of cardiovascular side effects of the new tricyclic antidepressant tianeptine. A double-blind, placebo-controlled study in young healthy volunteers. AB - In a double-blind, placebo-controlled, crossover study, the effects of therapeutic doses of the new tricyclic antidepressant tianeptine on cardiovascular function were closely monitored in 21 healthy volunteers during a 2-week treatment period. Blood pressure measurements, ECG recording, 24-h Holter monitoring, and echocardiography were carried out at 1-week intervals. Isotopic ventriculography was measured twice under each treatment. Tianeptine did not produce orthostatic hypotension or increase heart rate. No ECG changes could be observed and the cardiac conduction time remained unchanged. One subject presented with an increase in frequency of ventricular premature beats that could not be definitely attributed to the drug. Cardiac output assessed at rest and after a bicycle exercise stress test was not altered. The present study suggests that tianeptine is a tricyclic antidepressant endowed with less cardiac toxicity than classical tricyclic antidepressants. PMID- 2306748 TI - Influence of tetrahydro-9-aminoacridine on excitatory amino acid release. AB - Alzheimer's disease may be associated with an early and clinically relevant degeneration of some cortical excitatory amino acid-releasing neurons. Tetrahydro 9-aminoacridine (tacrine) might be an effective drug for the treatment of the disease. Various pharmacological paradigms (in rats) related to amino acid release are shown here to be modified both in vivo and in vitro by the drug. These effects are only observed with high concentrations, so it is unlikely that tacrine acts through amino acid release in humans. PMID- 2306749 TI - Primidone in the long-term treatment of essential tremor: a prospective study with computerized quantitative analysis. AB - The long-term efficacy of primidone (375-750 mg/day) in essential tremor was evaluated prospectively in 11 patients who had shown a favorable response to 4 week treatment with the drug under placebo-controlled conditions. On accelerometric evaluation, the magnitude of tremor after 3, 6, and 12 months on primidone was still significantly reduced compared with the initial placebo period. After discontinuation of primidone, tremor amplitude reverted to the placebo levels. Some loss of efficacy during long-term administration, however, was suggested by the results of self-assessment, physician's assessment, and performance tests. Three patients discontinued prematurely the drug because the sedative effects outweighed the potential therapeutic benefit. Side effects (especially drowsiness and sedation) were common at 4 weeks and 3 months but tended to subside thereafter. It is concluded that primidone retains at least part of its tremorolytic effect for up to 1 year, although the overall clinical benefit is limited in most patients. PMID- 2306750 TI - Treatment of Tourette's syndrome with calcium antagonists. AB - Six males and one female with chronic tic disorders, whose ages ranged from 12 to 31 years, were evaluated before treatment, after 1 month on placebo, after a single 10 mg nifedipine dose (three patients), and monthly while on flunarizine 10-15 mg (mean dose of 13 mg). None of the patients receiving nifedipine improved, but treatment with flunarizine significantly decreased both motor and phonic tic severity and frequency in all but one patient. Side effects included mild transient headaches in one patient, depression in one, and bradykinesia in two. Although a double-blind study is essential to validate our findings, results suggest that flunarizine is a useful drug in the treatment of Gilles de la Tourette syndrome. PMID- 2306751 TI - Effects of long-term amantadine treatment on clinical symptoms and EEG of a patient in a vegetative state. PMID- 2306752 TI - Interleukin-2-dependent long-term cultures of low-density lymphocytes allow the proliferation of lymphokine-activated killer cells with natural killer, Ti gamma/delta or TNK phenotype. AB - We have developed a culture system for "long-term" growth of human lymphokine activated killer (LAK) cells exhibiting an elevated, wide-spectrum antitumor cytotoxicity. The system allows the exponential growth of monocyte-depleted low density lymphocytes in the presence of human serum and recombinant human interleukin-2 (10(3) U/ml), alone or in combination with interleukin-1 alpha or beta (both at 10 U/ml). Eighteen cultures were established from 18 normal adult donors. The membrane phenotypes of the final LAK cell population, assessed by a panel of monoclonal antibodies (mAb), consist of three main types: (a) NKH-1+, Ti alpha/beta-, Ti gamma/delta-, and CD3- lymphocytes; (b) NKH-1+, Ti alpha/beta-, Ti gamma/delta+, and CD3+ lymphocytes and (c) NKH-1+, Ti alpha/beta+, Ti gamma/delta- and CD3+ lymphocytes. Northern blot analysis showed that all these cell populations express relatively high levels of perforin RNA, particularly cells exhibiting the first phenotype. This culture system may provide a tool for cellular and molecular studies on the mechanisms of antitumor cytotoxicity, as well as the basis for new adoptive immunotherapy protocols in advanced center. PMID- 2306753 TI - Adoptive immunotherapy of a mouse colon carcinoma with recombinant interleukin-2 alone or combined with lymphokine-activated killer cells or tumor-immune lymphocytes. Survival benefit of adjuvant post-surgical treatments and comparison with experimental metastases model. AB - We have used a BALB/c colonic adenocarcinoma (C-26) to evaluate the therapeutic potential of recombinant interleukin-2 (rIL-2) at high and low dosages in combination with or without lymphokine-activated killers (LAK) or tumor-specific, immune lymphocytes in either an adjuvant spontaneous or an artificial metastasis system. Most (approximately 80%) of the mice that underwent s.c. C-26 tumor excision systemic treatment with low-dose rIL-2 (3 x 10(4) U/day, i.p.) increased the survival rate to 31% as compared to 21% (not significant) in excised controls while administration of high-dose rIL-2 (8 x 10(4) U/day) led to 53% survival (P less than 0.001). Both LAK cells and C-26-tumor-immune lymphocytes given during rIL-2-treatment significantly increased the effects of rIL-2 at the low but not at the high-dose, with tumor-immune effectors resulting in the highest percentage (63%) of cures. When mice bearing 3-day artificial lung metastases of C-26 cells were treated wtih low- or high-dose rIL-2, in combination with or without LAK or tumor-immune lymphocytes, a highly significant reduction or abrogation of the number of lung foci was observed with all treatments, including those involving or tumor-immune lymphocytes alone. Assessment of survival benefit in these mice, however, showed survival prolongation, with 20% cures achieved by low-dose rIL-2 alone and up to 65% cures by LAK in combination with low-dose rIL-2. In this system of artificial metastasis high-dose rIL-2 alone increased the survival time but failed to cure the animals, and the addition of LAK was ineffective whereas that of tumor-immune lymphocytes led to 80% cure. These results suggest that tumor-immune lymphocytes are more effective than LAK when combined with rIL-2 and that caution is necessary in extrapolating findings obtained in artificial metastasis models. PMID- 2306754 TI - Mouse tumors are heterogeneous in their susceptibility to syngeneic lymphokine activated killer cells and delineate functional subsets in such effectors. AB - We have analyzed whether lymphokine-activated killer (LAK) cells, generated from C57BL/6J (B6) spleen cells at different times after recombinant interleukin-2 (rIL-2) culture, could be heterogeneous in their ability to lyse a variety of tumor targets. When tested 3 days after exposure to 250 U/ml rIL-2 (day-3 LAK cells) a significant lysis was detected with the natural-killer(NK)-sensitive YAC lymphoma, the NK-resistant P815 mastocytoma, three different syngeneic melanomas and a syngeneic fibrosarcoma (group 1 targets), whereas no lysis was observed with a reticulum cell sarcoma, two different lymphomas or concanavalin A blasts, all of B6 origin (group 2 targets). LAK cells cultured for 5 days, however, lysed group 2 targets and showed a parallel increase of cytotoxic activity against group 1 targets. At day 7, LAK activity declined on all targets examined. In cold target inhibition studies, the lysis of group 1 tumor targets by day-3 or day-5 LAK cells could be inhibited only by group 1 and not by group 2 unlabelled tumor cells. All group 1 tumors could effectively compete each other. Conversely, the lysis of group 2 tumor targets by day-5 LAK cells was inhibited by both group 1 and group 2 targets. These data indicate the presence of separate LAK effectors that appear to arise with different time kinetics and have different recognition structures. In vitro antibody depletion at the effector level showed that day-3 LAK cells with cytotoxic activity against group 1 tumors were ASGM1+. Day-5 LAK cells included both ASGM1+ and Lyt2+ effectors and both populations, although to a different extent, contributed to the lysis of all targets. Our results indicate that LAK cells are functionally heterogeneous. This heterogeneity is defined by their susceptible target cells and cannot be ascribed to different (Lyt2+ versus ASGM1+) lineages. PMID- 2306755 TI - Natural killer and lymphokine-activated killer cell functions in chronic myeloid leukemia. AB - The natural killer (NK) and lymphokine-activated killer (LAK) cell activities of peripheral blood lymphocytes from chronic myeloid leukemia (CML) patients in remission and from healthy donors have been studied. Regression analysis to compare both cytotoxic responses in individual donors and the frequency of LAK cell precursors was also carried out. About 42% of CML patients in remission showed low NK activity (less than the mean percentage NK activity of healthy donors--2 SD) and were categorised as low NK responders. The stage of remission or the drugs used to bring about remission did not influence the NK status. The LAK activity of low NK as well as normal NK responder CML patients was significantly low against the NK-sensitive K562 cell line and the NK-resistant VIP (melanoma) and T-24 (bladder carcinoma) tumor targets, as assessed by linear regression analysis. Allogeneic leukemic cells were more resistant to killing, especially by patients' LAK cells. The frequency analysis of LAK cell precursors revealed a significant reduction in the LAK cell progenitor frequency in CML patients in remission. PMID- 2306757 TI - Selection and management of heart transplant patients. PMID- 2306758 TI - Nonselective preoperative digital subtraction angiography of internal mammary arteries. AB - In preparation for coronary bypass surgery, digital subtraction angiography (DSA) was used to assess the caliber of the left and right internal mammary arteries and to exclude stenoses of their feeding arteries. In 100 patients (86 males, mean age 56 +/- 9 years) DSA was performed with a Siemens Digitron 2 device. A frontal projection was used in 18 patients, and a 10-20 degree right anterior oblique projection was used in 82 patients. The flow was 10 to 25 ml/sec; 20 ml was injected in 45 patients, 30 ml in 41, 40 ml in 5, 50 ml in 8, and 60 ml in 1 patient. Judged on the proximal third, visualization of the left and the right internal mammary artery was good in 80 and 72, fair in 17 and 20, and bad in 3 and 8 arteries, respectively. The diameter (mm) was 2.7 +/- 0.4 (range 1.8-3.4) and 2.7 +/- 0.3 (range 2.0-3.5), and visible length (cm) was 8 +/- 5 (range 1-24) and 9 +/- 4 (range 2-22) for the two arteries, respectively. The 10-20 degree right anterior oblique view separated the left internal mammary artery better from the descending aorta than the frontal view. In more pronounced right anterior oblique views the ascending aorta interfered with the right internal mammary artery. The quality was not different with 20 ml or 30 ml injections. The feeding arteries could not be assessed in 4 patients. One left subclavian artery was found occluded at the orifice. Incidentally, 2 distal right subclavian stenoses and 2 carotid stenoses were detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306756 TI - Addition of interleukin-2 in vitro augments detection of lymphokine-activated killer activity generated in vivo. AB - The in vivo administration of repetitive weekly cycles of interleukin-2 (IL-2) to patients with cancer enhances the ability of freshly obtained peripheral blood lymphocytes (PBL) to lyse both the natural-killer(NK)-susceptible K562 and the NK resistant Daudi targets. Lysis of both targets is significantly augmented by inclusion of IL-2 in the medium during the cytotoxicity assay. This boost is much greater for cells obtained following the in vivo IL-2 therapy than for cells obtained prior to the initiation of therapy or for cells from healthy control donors. In addition to direct lytic activity, the PBL obtained following in vivo IL-2 show a rapid increase in lymphokine-activated killer (LAK) activity with more prolonged in vitro IL-2 exposure, indicating that LAK effectors primed in vivo respond with "secondary-like" kinetics to subsequent IL-2 in vitro. Lymphocytes from healthy control individuals, cultured in IL-2 under conditions attempting to simulate the in vivo IL-2 exposure, function similarly to PBL obtained from patients following IL-2, in that low-level LAK activity was significantly boosted by inclusion of IL-2 during the cytotoxic assay and the cells also responded with secondary-like kinetics to subsequent IL-2 in vitro. The augmentation of the LAK effect was also dependent on the dose of IL-2 added during the 4-h 51Cr-release cytotoxicity assay, with higher doses of IL-2 having a more pronounced effect. While continuous infusion of IL-2 induces a greater cytotoxic potential per milliliter of blood obtained from patients, the peak serum IL-2 levels attained are greater with bolus IL-2 infusions. These pharmacokinetic results, together with the IL-2 dose dependence of LAK activity generated in vivo shown in this report, suggest that a combination of treatment with bolus IL-2 infusions superimposed on continuous IL-2 infusion may transiently expose IL-2 dependent LAK cells, activated in vivo, to higher concentrations of IL-2, facilitating their in vivo cytotoxic potential. PMID- 2306759 TI - Restenosis after transluminal coronary angioplasty: a risk factor analysis. AB - In order to determine the relationship of restenosis following percutaneous transluminal coronary angioplasty (PTCA) to risk factors such as hypercholesterolemia, hyperglycemia, smoking, and weight, we performed a univariate analysis to test the association of these variables with restenosis in 723 patients who had percutaneous transluminal coronary angioplasty and follow-up catheterization. Cholesterol levels were higher in younger and female subjects (less than 0.0001). Initial cholesterol did not predict restenosis, and follow-up cholesterol levels showed an inverse relationship with restenosis (P less than .02). There was a trend (P less than .09) toward decreased restenosis in those who were active smokers at the time of follow-up catheterization. No differences were seen in diabetics with hyperglycemia, in both treated and untreated groups (P = NS). A stepwise multiple logistic regression was used to simultaneously test the association of the above risk factor variables to restenosis. None of the interactions were found to be significant, except cholesterol at follow-up (P = .001). Therefore, the status of serum cholesterol, blood sugar, smoking, and weight during the time of PTCA and at follow-up catheterization may be unimportant in predicting restenosis. Thus, we conclude 1) that to better determine the effect of these variables on restenosis, they should be estimated at times other than follow-up and 2) that the pathophysiological mechanism of restenosis may have different risk factors than progression of atherosclerotic coronary artery disease. PMID- 2306760 TI - Balloon entrapment in a coronary artery: potential serious complications of balloon rupture. AB - We report a case of balloon catheter rupture with subsequent entrapment during percutaneous transluminal coronary angioplasty. The presence of a calcified, distal lesion is believed to have prevented withdrawal of the broken catheter. A nonsurgical retrieval technique, using a second dilation system, was used to free the catheter. PMID- 2306761 TI - Coronary artery dissection caused by angioplasty balloon rupture. AB - Three cases of coronary angioplasty balloon rupture complicated by coronary artery dissection are described. Factors that may predispose to this previously undescribed and potentially devastating complication are discussed. PMID- 2306762 TI - False coronary dissection with the new Monorail angioplasty balloon catheter. AB - During percutaneous transluminal coronary angioplasty, the appearance of persistent staining in the vessel by contrast media suggests coronary dissection. We report seven patients in whom a false image of severe coronary dissection was observed during angioplasty performed with the new Monorail balloon catheter. This image emerges at the moment of balloon inflation, is distally located to the balloon, and disappears with balloon catheter deflation. No complications were associated with the appearance of this image. PMID- 2306763 TI - Angioplasty of recent total coronary occlusions: cardiac death can occur in "low risk" cases. AB - Revascularization by angioplasty of total coronary artery occlusions is generally thought to be relatively safe in experienced hands. Although success rates are lower than with diseased but patent vessels, reasonable success can be expected. In this report, different events led to a sudden and fatal outcome in two patients with total coronary occlusions subtending recently infarcted, but still viable, areas of myocardium. The cases and procedural details are presented. PMID- 2306764 TI - Percutaneous balloon valvuloplasty of a stenosed mitral bioprosthesis. AB - A 62-year-old woman with disabling mitral prosthetic stenosis underwent percutaneous balloon valvuloplasty. The transvalvular gradient preoperatively was 22 mm Hg and was reduced to 6 mm Hg after the valvuloplasty. the valve area was increased from an initial value of 0.77 cm2 to 1.53 cm2. No complications occurred related to the Further studies are necessary to ascertain the indications and long-term results of percutaneous valvuloplasty on bioprosthesis in the mitral position. PMID- 2306765 TI - Ventricular fibrillation during coronary angiography: reduced incidence with nonionic contrast media. AB - Ventricular fibrillation during coronary angiography with Renografin-76 has been attributed to the high osmolar ionic and calcium binding additive properties. Isovue-370 is a new low osmolar nonionic contrast medium lacking calcium binding additives. The present investigation compared the incidence of contrast media induced ventricular fibrillation in patients undergoing coronary angiography with Renografin-76 to that with Isovue-370. Group I consisted of 2,000 consecutive patients undergoing coronary angiography with Renografin-76, and group II consisted of 2,000 subsequent consecutive patients in whom Isovue-370 was employed as the contrast medium. There was no significant difference between groups I and II with respect to volume of contrast media used per patient (125 +/ 35 vs. 140 +/- 45 ml), age (63.5 +/- 15 vs. 60 +/- 17 years), sex (74% male vs. 76% male), ejection fraction (55% vs. 55%), valvular heart disease (8% vs. 9%), prior coronary artery bypass graft surgery (5.8% vs. 5%), or extent of coronary artery disease. Contrast media-induced ventricular fibrillation occurred in 20 patients in group I (incidence 1%), whereas eight episodes occurred in group II (incidence 0.4%) (P less than 0.03). Thus the present investigation suggests that the incidence of ventricular fibrillation during coronary angiography can be significantly decreased by using low osmolar nonionic contrast media lacking calcium binding additives. PMID- 2306766 TI - Single coronary artery associated with annuloaortic ectasia and ventricular septal defect. AB - A 60-year-old man with a single left coronary artery associated with an annuloaortic ectasia and a ventricular septal defect is described. He presented with severe heart failure and underwent open-heart surgery during which all these entities were confirmed. PMID- 2306767 TI - Anomalous aortic origin of the left anterior descending coronary artery with dilated cardiomyopathy. AB - Serious complications such as angina pectoris and myocardial infarction in patients with anomalous origin of a coronary artery have been documented. However, this anomaly with dilated cardiomyopathy is very rare. We present the first case of anomalous origin of the left anterior descending coronary artery with dilated cardiomyopathy. PMID- 2306768 TI - Venobronchial fistula: a complication associated with central venous catheterization for chemotherapy. AB - We report a case in which a venobronchial fistula developed 4 months after insertion of a silicone rubber chronic central venous catheter for chemotherapy administration. In retrospect, the tip of the catheter was in the azygous vein rather than in the superior vena cava. The suboptimal position of the catheter tip, in combination with the infusion of sclerosing chemotherapeutic agents and hyperalimentation solution, may have predisposed the patient to this complication. Accurate localization of the tip of central venous catheters at the time of placement should minimize catheter-related complications, including the rare complication of venobronchial fistula. After placement of chronic central venous catheters, biplanar chest X-rays should be obtained to determine catheter tip location prior to the instillation of chemotherapeutic agents. Any residual questions concerning the catheter tip location after biplanar X-rays should be addressed by prompt venography through the catheter. PMID- 2306769 TI - Atrialization of right ventricular pressure during acute cardiac allograft rejection. AB - We describe a patient who, during an episode of acute cardiac rejection, developed such severe systolic dysfunction that there was transient near-adynamic function of the right ventricle. This right ventricular dysfunction was reflected hemodynamically by the unusual finding of atrialization of right ventricular pressures. The patient's cardiac function returned to normal after treatment with extensive immunotherapy. PMID- 2306770 TI - Antegrade catheter snare for retrograde catheterization of the left ventricle: a new technique to facilitate balloon aortic valvuloplasty. PMID- 2306771 TI - Guiding catheter selection for right coronary artery angioplasty. PMID- 2306772 TI - Re: "Percutaneous Transluminal Angioplasty of Stenotic Saphenous Vein Right Coronary Bypass Grafts Utilizing a Peripheral Balloon Dilatation Catheter without a Guiding Catheter". PMID- 2306773 TI - Emergency cardiopulmonary bypass support in patients with cardiac arrest in the catheterization laboratory. AB - Cardiac arrest in the catheterization laboratory is fatal if unresponsive to advanced cardiac life support (ACLS). Seven patients not responding to ACLS following cardiac arrest in the catheterization laboratory underwent percutaneously instituted cardiopulmonary bypass support. Cardiac arrest occurred following abrupt closure postcoronary angioplasty in three patients, during cardiogenic shock in three patients, and during diagnostic angiography in one patient. Cardiopulmonary bypass was instituted 10-45 min (mean, 21 min) following the onset of cardiac arrest. Flows on bypass ranged from 4.0 to 5.2 liter/min. Mean blood pressure ranged from 70 to 110 mm Hg on bypass. Six of the seven patients regained consciousness after the institution of bypass. Acid-base balance was normalized in all patients. Coronary bypass surgery was subsequently performed in three patients and coronary angioplasty in two. Four patients survived. One patient died following coronary bypass surgery. Two patients, who were not suitable candidates for revascularization, expired. Total bypass time was 1.5-8.5 hr (mean, 2.7 hr). At a mean follow-up of 6 months, all four survivors are alive and asymptomatic or NYHA class 1. We conclude that cardiopulmonary bypass support 1) can stabilize patients following cardiac arrest in the catheterization laboratory, 2) can facilitate emergency coronary angioplasty or transfer to the operating room for coronary bypass surgery, and (3) can improve survival in patients unresponsive to ACLS when instituted early following cardiac arrest in the catheterization laboratory. PMID- 2306774 TI - Spontaneous reversal of flow through jeopardized collateral vessels during non-Q wave myocardial infarction. AB - This case report documents that, when a severely diseased donor artery occludes, sufficient spontaneous reversal of flow through the collaterals can occur to prevent an extensive and possibly fatal transmural infarction. PMID- 2306775 TI - Assessment of the "long sheath" technique for percutaneous aortic balloon valvuloplasty. AB - A 100 cm-long 16.5 F valvuloplasty catheter introducer was assessed as an adjunct for percutaneous transluminal aortic valvuloplasty (PTAV) via the femoral artery in 31 patients with severe aortic stenosis. Observed improvements in peak systolic gradient (81.6 +/- 29.9 mm Hg vs. 35.5 +/- 16.0 mm Hg, P less than 0.000001) and aortic valve area (0.6 +/- 0.4 cm2 vs. 1.0 +/- 0.6 cm2, P less than 0.00001) were similar to those achieved in a control group (C) of 17 patients in which no femoral sheath was used. However, a shorter procedure duration (211 +/- 81 min vs. 117 +/- 30 min, P less than 0.001) and a reduced rate of vascular complications at the femoral puncture site (41% vs. 6.5%) were observed in patients in whom the long sheath (LS) technique was used. The frequency of other PTAV-related complications was comparable (C = 35%, LS = 29%, P = n.s.). Other technical advantages of this device are: 1) prevention of looping and bending of the balloon catheter in tortuous vessels and easy positioning of the balloon across the aortic orifice provided by the LS trackability, 2) stabilisation of the balloon during inflation, 3) monitoring of supravalvular aortic pressure provided by the side-arm of the LS and reliable measurement of systolic gradient, and 4) the ability to perform aortograms without the need of another catheter in the ascending aorta. Thus, in our experience, the long sheath technique is a valuable adjunct for PTAV. PMID- 2306776 TI - Effectiveness of the Arani double-loop guiding catheters in angioplasty of aorto coronary vein grafts. AB - Double-loop guiding catheters have been used for angioplasty of aorto-coronary vein grafts (VG) or grafted arteries through the VG in 31 cases. A catheter with a 90 degrees primary curve was usually the best choice for angioplasty of the VG to the right coronary artery (RCA). For angioplasty of the VG to the left coronary artery branches (LCA), a 90 degrees primary curve was used when the proximal segment of the VG was oriented horizontally and a 75 degrees (USCI, C.R. Bard, Inc., Billerica, MA) was used when the proximal segment was directed superiorly. Angioplasty of 32 lesions was attempted in 31 patients. These catheters provided good "back-up" in angioplasty of 30 lesions (94%). The lesions were crossed with balloon catheters in 29 cases (91%). There was one acute VG occlusion requiring coronary artery bypass graft (CABG) surgery, a complication not attributed to the guiding catheter. We conclude that Arani guiding catheters provide strong back-up, are helpful in angioplasty of the vein grafts, and could be used as the primary choice for VG angioplasties. PMID- 2306777 TI - New steerable, ultra-low-profile, fixed-wire angioplasty catheter: initial experience with the Cordis Orion Steerable PTCA Balloon Catheter. PMID- 2306778 TI - Doubtful arterial puncture during cardiac catheterisation in cyanotics. PMID- 2306779 TI - Ruptured aneurysm of the sinus of Valsalva. PMID- 2306780 TI - Mitral valve rupture during percutaneous dilatation of aortic valve stenosis: an avoidable complication. PMID- 2306781 TI - Coronary angioplasty--unstable lesions and prolonged balloon inflation time. AB - One of the most important complications after percutaneous transluminal coronary angioplasty is the abrupt closure of the dilated vessel (unstable lesion). The treatment of choice for this complication is a new dilation, but unfortunately many of these cases require immediate surgery to avoid an acute myocardial infarction. Prolonged balloon inflations have been suggested to control this kind of complication. In order to discover the effect of prolonged inflations on the incidence of unstable lesions we studied 439 patients enrolled in two groups: Group I (195 patients and 207 arteries) treated with balloon inflation time less than 40 sec per session and Group II (244 patients and 265 arteries) treated with inflation time over 60 sec since the first series of inflations. As a result there was a significantly lower incidence of unstable lesions and immediate surgery in Group II without an increase in the incidence of diffuse ischemia. PMID- 2306782 TI - Comparison of 5F and 7/8F catheters for left ventricular and coronary angiography. AB - Fifty-two patients were randomized into two groups of 26 to the use of either 5 or 7/8F catheters for their first left heart cardiac catheterization. Clinical characteristics for the two groups were similar. 5F catheters were significantly inferior to 7/8F catheters in terms of torque control (P less than .001), ease of engaging coronary ostia (P less than .001), and quality of angiograms (P less than .05). Nine patients in the 5F group required a change to 7/8F catheters for completion of the procedure. There was no difference in procedure time or fluoroscopy time between the groups. Time to haemostasis was significantly shorter in the 5F group (P less than .01), but there was no difference between groups with respect to haematoma formation or rebleed after haemostasis. We conclude the slight advantage of 5F catheters in terms of haemostasis is outweighed by many disadvantages. Their routine use in cardiac catheterization, at least at this time, cannot be recommended. PMID- 2306783 TI - Pinhole balloon rupture during coronary angioplasty causing rupture of the coronary artery. AB - We report a case of pinhole balloon rupture during percutaneous transluminal coronary angioplasty using one of the newer catheters. Pinhole balloon rupture resulted in rupture and occlusion of the vessel being dilated. PMID- 2306784 TI - Unusual guidewire maneuver to enter an acute angulation during complex percutaneous transluminal coronary angioplasty. AB - Guidewire manipulation may be the deciding factor for success in percutaneous transluminal coronary angioplasty (PTCA) A case involving a complex lesion forming an acute angle within the left anterior descending (LAD) coronary artery, which precluded guidewire advancement, is presented. Successful dilatation was achieved after an unusual guidewire maneuver. PMID- 2306785 TI - Measles in Canada--1988. PMID- 2306786 TI - The effect of hydrogen bonds on the conformation of glycosphingolipids. Methylated and unmethylated cerebroside studied by X-ray single crystal analysis and model calculations. AB - The conformation and molecular packing of permethylated beta-D-galactosyl-N octadecanoyl-D-spingosine (cerebroside) was determined by X-ray single crystal analysis at 185 K (R = 0.16). The lipid crystallizes in the orthorhombic space group P2(1)2(1)2(1) with the unit cell dimensions a = 8.03, b = 7.04 and c = 88.10 A. The four molecules in the unit cell pack in a bilayer arrangement with tilting (48 degrees) hydrocarbon chains. The direction of the chain tilt alternates in the two bilayer halves and in adjacent bilayers. In order to define the effect of hydrogen bonds on the molecular conformation the structural features of the permethylated cerebroside are compared with that of unsubstituted cerebroside (I. Pascher and S. Sundell (1977) Chem. Phys. Lipids 20, 179). It is shown that methylation of the hydrogen donor groups does not affect the conformation of the ceramide part. However, by abolishing the intramolecular hydrogen bond between the amide N--H group and the glycosidic oxygen the galactose ring changes its orientation from layer-parallel to layer perpendicular. Calculations using molecular mechanics, MM2(87), show that in natural cerebroside the intramolecular hydrogen bond stabilizes the theta 1 = syn-clinal conformation about the C(1)--C(2) sphingosine bond by 2-2.5 kcal/mol compared to other staggered conformations. The significance of the L shape of the native cerebroside, making both the carbohydrate and polar ceramide groups accessible as a binding epitope in recognition processes, is discussed. PMID- 2306787 TI - Interaction of 7,7,8,8-tetracyanoquinodimethane with diacylphosphatidylcholines and -phosphatidylglycerols. A photoacoustic Fourier transform infrared study. AB - 7,7,8,8-Tetracyanoquinodimethane (TCNQ) was incorporated in fully hydrated liposomes of the following pyrene-containing as well as non-labelled phospholipids: 1-palmitoyl-2-[10-(pyren-1-yl)decanoyl]-sn-glycero-3-phosphatid ylc holine (PPDPC), 1-palmitoyl-2-[10-(pyren-1-yl)decanoyl]-sn-glycero-3 phosphatidyl- rac'- glycerol (rac'-PPDPG), 1-palmitoyl-2-[10-(pyren-1 yl)decanoyl]-sn-glycero-3-phosphatidyl- sn-3'- glycerol (3'-PPDPG), 1-[10-(pyren 1-yl)decanoyl]-2-palmitoyl-sn-glycero-3-phosphatidyl- sn-3'- glycerol (3'-PDPPG), 1-[10-pyren-1-yl)decanoyl]-2-palmitoyl-sn-glycero-3-phosphatidyl-s n-1'- glycerol (1'-PDPPG), 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2 dipalmitoyl-sn-glycero-3-phosphatidyl-rac'-glycerol (rac'-DPPG). Lyophilized charge-transfer (CT) complexes of TCNQ with phospholipids were examined by Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS). Due to the spectral changes observed in the vibrational bands originating from the CH2 and C = O stretching vibrations, and the bands associated with the polar headgroup of the phospholipids it is evident that TCNQ has only a minor perturbing effect on the hydrocarbon chains. However, the molecular interaction between TCNQ and phospholipids is seen in the polar headgroup region. The donated electrons are most likely located on the oxygens of the phosphate group in the polar head. As judged from the present infrared data interactions of TCNQ with phosphatidylcholines (PC) and phosphatidylglycerols (PG) differ. For PG the complex formation produces a second strong C = O stretching band at approx. 1710 cm-1 in addition to the band at approx. 1735 cm-1 indicating a specific molecular interaction in the interfacial region. PMID- 2306788 TI - Palmitoyl carnitine can exist in lamellar and hexagonal phases. AB - Carnitine is a necessary cofactor for the transport of fatty acids across the inner mitochondrial membrane. The behaviour in a buffer solution of the acyl carnitine, palmitoyl carnitine, has been investigated. Palmitoyl carnitine is amphiphilic and resembles, in some structural respects, a lysolecithin. X-ray diffraction studies showed that palmitoyl carnitine in buffer at a low temperature formed a gel-phase bilayer with fully interdigitated hydrocarbon chains perpendicular to the bilayer surface. The bilayer thickness increased slightly as water content increased due to a reorientation of the carnitine portion. As temperature was increased a transition occurred to a hexagonal (H1) phase with buffer solution separating cylinders of palmitoyl carnitine. The transition occurred over a broad temperature range of approximately 20 degrees C. PMID- 2306789 TI - Thickness measurements of single walled dimyristoyl phosphatidylcholine vesicles by neutron scattering. AB - A method of deriving by neutron scattering thicknesses of lamellae in suspensions has been applied to single-walled vesicles of dimyristoyl phosphatidylcholine. The contrast variation method, based on data obtained for a range of isotope mixtures, has been used to extract a dimension Dw related to the lipid bilayer thickness and a measure alpha of the difference of density within the lamellae. Isotope mixtures for the lipid were used to optimize the information available. Dw is compared with results from multilayer stacks of lipid layers. The thickness for the low temperature L beta, structure has been observed to be higher than for the high temperature L alpha structure. Preliminary experiments on the kinetics of the mixing of the lipid isotope species are reported, and evidence is shown that the species are not segregated for lipids either above or below the transition temperature. PMID- 2306790 TI - Physicochemical and pharmacokinetic parameters of seven lipophilic chlorambucil esters designed for brain penetration. AB - This report describes the physicochemical and pharmacokinetic parameters of seven chlorambucil esters, which were compared with those of chlorambucil. These esters were designed as chlorambucil prodrugs to increase the brain penetration and concentration vs time profile of chlorambucil within the CNS for potential treatment of brain tumors. They include four aliphatic esters from one to eight carbon chains in length (chlorambucil-methyl, -propyl, -hexyl, and -octyl esters) and three aromatic esters, including the phenylmethyl, phenylethyl and prednisolone ester of chlorambucil, prednimustine. The esters were lipophilic and possessed log octanol:water partition coefficients (log P values) that ranged from 4.05 to greater than 8.0. All retained alkylating activity, which was reduced compared with that of chlorambucil. In addition, all were metabolized in vivo in the rat to yield chlorambucil alone. Measurement of the in vitro rate of ester hydrolysis of the compounds to yield chlorambucil in rat plasma demonstrated that short-chain aliphatic and aromatic chlorambucil esters were rapidly broken down to their parent compound. The plasma half-lives of the compounds increased with the increasing length and complexity of their ester chain. This may have been related to an increase in the binding of the long-chain esters to plasma proteins, protecting the ester from nonspecific plasma esterases, and to a reduced affinity of plasma esterases to these esters. Pharmacokinetic analysis of chlorambucil-hexyl, -octyl, and -prednisolone esters by HPLC demonstrated that following their intravenous administration in the rat (in doses equivalent to equimolar chlorambucil, 10 mg/kg), they yielded only low concentrations of active compounds in plasma and brain. The brain:plasma ratio of these was low and similar to that of chlorambucil, and no ester demonstrated anticancer activity superior to that obtained after the administration of equimolar chlorambucil (5 mg/kg i.v., days 1-5) against brain-sequestered Walker 256 carcinosarcoma in the rat. PMID- 2306791 TI - Pharmacokinetics of chlorambucil-tertiary butyl ester, a lipophilic chlorambucil derivative that achieves and maintains high concentrations in brain. AB - Equimolar doses of chlorambucil (10 mg/kg) and the lipophilic chlorambucil derivative, chlorambucil-tertiary butyl ester (13 mg/kg), were given i.v. to rats. Plasma and brain concentrations of chlorambucil and its active metabolites, 3,4-dehydrochlorambucil and phenylacetic mustard, as well as of chlorambucil tertiary butyl ester were then determined by HPLC between 2 and 240 min after drug administration. Chlorambucil demonstrated a monophasic disappearance from plasma following its administration, with a half-life of 28 min. Significant amounts of phenylacetic mustard were detected after 15 min, and this agent maintained high levels of active compounds in plasma throughout the study. Only low concentrations of chlorambucil and phenylacetic mustard were detected in brain between 2 and 120 min. Following equimolar chlorambucil-tertiary butyl ester administration, it rapidly disappeared from plasma, with a half-life of approximately 2 min, and maintained low plateau concentrations between 15 and 120 min after treatment. It was not detected thereafter, although significant amounts of chlorambucil and phenylacetic mustard were detected throughout the study. Significant amounts of chlorambucil-tertiary butyl ester entered and remained within the brain, achieving a peak concentration at 15 min and disappearing thereafter with a half-life of 37 min. Low levels of chlorambucil and phenylacetic mustard were also detected. Calculated from the areas under the concentration vs time curves of total active compounds derived from chlorambucil and chlorambucil-tertiary butyl ester in brain and plasma, the brain:plasma concentration integral ratios were 0.018 and 0.68, respectively. Following equimolar doses of chlorambucil and chlorambucil-tertiary butyl ester, a 7-fold greater concentration integral was achieved by chlorambucil-tertiary butyl ester in brain at a 5-fold lower plasma concentration integral. Chlorambucil-tertiary butyl ester may be of value in the treatment of brain-sequestered tumors. PMID- 2306793 TI - In vitro chemosensitivity testing of Fotemustine (S 10036), a new antitumor nitrosourea. AB - Fotemustine (S 10036) is a new anti-tumor nitrosourea characterized by a phosphonoalanine carrier group coupled to the nitrosourea moiety, which potentially increases the cellular penetration of the drug. Using human tumor cell lines, the activity of S 10036 was compared with that of the more established nitrosoureas BCNU and CCNU. Growth-inhibiting effects were evaluated by the [3H]-thymidine incorporation test. In a panel of 12 human cancer cell lines [melanoma (4), ovary (2), head and neck (3), lung (1), bladder (1), breast (1)], the dose-response curves of S 10036 (0-100 microM) were similar to those obtained with equimolar concentrations of BCNU and CCNU; they indicated a moderately more marked effect for two and an equal effect for six melanoma cell lines with S 10036 as compared with BCNU. Moderate but significant synergistic combinations were obtained when S 10036 (0-80 microM) and CDDP (0-100 microM) or DTIC (250-6,500 microM) were combined in melanoma cell lines. In conclusion, the new nitrosourea S 10036 shows promising activity, particularly against human melanoma cell lines. PMID- 2306792 TI - Protective effects of fructose-1,6-diphosphate on acute and chronic doxorubicin cardiotoxicity in rats. AB - The effects of fructose-1,6-diphosphate, an intermediate metabolite of glycolysis, on acute and chronic cardiotoxicity of doxorubicin were investigated in rats. In the acute study, urethane-anaesthetized Wistar female rats treated with 10 mg/kg i.v. doxorubicin developed a widening of the S alpha T segment, an impairment of +dP/dtmax, and tachycardia. Pretreatment with 375 and 750 mg/kg i.p. fructose-1,6-diphosphate prevented the S alpha T segment from widening, whereas only 750 mg/kg i.p. significantly attenuated the heart rate increase. Chronic cardiomyopathy was induced over a 6-week period by weekly doses of 3 mg/kg i.v. doxorubicin, being characterized in vivo by the progressive enlargement of the S alpha T segment and the occurrence of histological alterations and in vitro by a marked impairment of the inotropic response elicited by adrenaline in isolated hearts from treated rats. Concurrent treatment with 150 and 300 mg/kg i.p. fructose-1,6-diphosphate thrice a week for 6 weeks did not lessen the chronic heart damage, whereas 600 mg/kg given i.p. significantly reduced the widening of the S alpha T segment and the severity of histological damage in vivo, as well as significantly improving the contractile responses of hearts in vitro. These findings suggest that the administration of fructose-1,6-diphosphate plays a protective role in the acute and chronic cardiotoxicity of doxorubicin in the rat. PMID- 2306794 TI - Effect of whole-body hyperthermia on hepatic cytochrome P450. AB - Currently, the combination of hyperthermia with a variety of chemotherapeutic agents and cytokines for the treatment of disseminated human malignancy is being examined. In this study we investigated the effects of 41 degrees-42 degrees C whole-body hyperthermia (WBH) and the cytokine interleukin-1 (IL-1) on cytochrome P450 in mice. At 24 h following 1 h of 41 degrees-42 degrees C WBH, IL-1 or combined treatment, hepatic microsomal cytochrome b5 and aminopyrine N demethylation were assayed. Cytochrome b5 activity was not significantly diminished by WBH, IL-1 or WBH + IL-1, but N-demethylation was suppressed by the combination of WBH + IL-1 and, to a lesser extent, by WBH alone. PMID- 2306795 TI - Phase I study of Brequinar sodium (NSC 368390) in patients with solid malignancies. AB - Brequinar sodium (DUP 785, NSC 368390) is a novel quinoline-carboxylic acid derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its novel chemical structure. This compound inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHO DH), which catalyzes the conversion of dihydroorotate to orotate, leading to a blockage in the pyrimidine de novo biosynthesis. A total of 43 patients received 110 courses of Brequinar sodium by short-term intravenous (i.v.) infusion, which was repeated every 3 weeks. Dose escalation was initially based on a modified Fibonacci scheme. After pharmacokinetic data from mice and man became available, a pharmacologically guided dose escalation was used; at toxic levels, dose escalation was applied on the basis of clinical judgement. The dose-limiting toxicities were myelosuppression, mucositis, skin rash, nausea and vomiting. The maximum tolerable doses for poor- and good-risk patients were 1,500 and 2,250 mg/m2, respectively. One mixed response was observed in a patient with papillary carcinoma of the thyroid. The recommended doses for phase II studies are 1,200 and 1,800 mg/m2 Brequinar sodium, given by a 1-h i.v. infusion every 3 weeks to poor- and good-risk patients, respectively. PMID- 2306796 TI - Relationship between the pharmacokinetics and toxicity of mitozolomide. AB - The cytotoxic drug mitozolomide has been found to cause unpredictably severe thrombocytopenia during phase I and II clinical trials. In an attempt to relate dose and pharmacokinetic parameters to toxicity, we measured plasma concentrations of mitozolomide in 14 patients with a range of malignancies. There were significant correlations (Spearman rank correlation test) between drug clearance and AUC and white blood cell nadir. The pharmacokinetic and toxicity data were not normally distributed; therefore, it was not possible to construct predictive nomograms for toxicity based on linear regression analysis. PMID- 2306797 TI - Efficacy and safety of high-dose cisplatin and cyclophosphamide with glutathione protection in the treatment of bulky advanced epithelial ovarian cancer. AB - Recent efforts to improve the response rates in advanced ovarian cancer with the use of high-dose cisplatin have been limited by unacceptable toxicity. Based on experimental and clinical studies indicating that reduced glutathione (GSH) is a protective agent against cisplatin-induced toxicity, a new high-dose regimen including GSH as a chemoprotector was designed in an attempt to improve the efficacy and therapeutic index of cisplatin. A total of 40 consecutive patients with stage III (bulky) and IV ovarian carcinoma were treated with cisplatin (40 mg/m2 daily for 4 consecutive days) and cyclophosphamide (600 mg/m2 i.v. on day 4). The treatment was repeated every 3-4 weeks for five courses unless progression or severe toxicity occurred. Before each cisplatin administration, patients received GSH (1,500 mg/m2) i.v. over 15 min, with a standard i.v. hydration (2,000 ml fluid) without diuretics. Debulking surgery was initially attempted in 18 patients and, after 2-3 courses, in 16 patients; it could not be carried out in 6 patients. Three patients were not evaluable for response because they prematurely discontinued their treatment. In all, 23 patients (62%) achieved complete clinical remission (negative second-look laparotomy in 16), with an overall (complete + partial) response rate of 86%; 2 patients achieved disease free status following second surgery. Nausea/vomiting was the most severe acute toxic effect; myelosuppression was acceptable. Renal impairment was effectively prevented by GSH. Neurotoxicity that was not associated with motor dysfunction was the most significant cumulative toxicity in patients (24/32) receiving 4-5 courses. The results of this study indicate that the use of GSH is a safe new method for high-dose cisplatin administration. This regimen is well-tolerated and very effective in ovarian cancer patients with bulky disease and warrants further evaluation. PMID- 2306798 TI - High-dose cisplatin in disseminated melanoma: a comparison of two schedules. AB - A total of 38 patients with metastatic melanoma received monthly chemotherapy with cisplatin at a dose of 200 mg/m2, per cycle; 14 received 20 mg/m2 cisplatin i.v. on days 1-5 and 24 were given 100 mg/m2 i.v. on days 1 and 8. Objective responses were seen in 2/14 treated on days 1-5 and in 5 of 22 evaluable subjects receiving cisplatin on days 1 and 8, for an overall response rate of 22%. The median survival of all patients was 6 months, with no significant difference observed between the two schedules. Severe neurotoxicity and myelosuppression were more common in patients treated on days 1-5. Two patients treated in this manner were bedridden due to neurotoxicity and four developed grade 4 leukopenia after the first cycle of chemotherapy. Only one patient treated with the divided dose schedule became leukopenic during the first cycle, and none of the patients were debilitated by neurotoxicity. Thrombocytopenia was statistically more severe. Nausea and vomiting, fatigue, ototoxicity, and paresthesia were seen with equal frequency. Very high doses of cisplatin can be delivered with acceptable toxicity using a divided-dose schedule. As the response rate on this schedule appeared to be comparable with that achieved on the more toxic consecutive 5-day schedule, the former deserves to be tested in diseases known to show a dose response to cisplatin. However, in melanoma, administration of 200 mg/m2 per course did not appear to be associated with a markedly improved response rate, compared with cisplatin alone at "standard" doses. PMID- 2306799 TI - The case of Vepesid overdosage in a patient with Hodgkin's disease. PMID- 2306800 TI - Changes in intracellular calcium during mechanical alternans in isolated ferret ventricular muscle. AB - Alternans in heart is important as pulsus alternans in cardiac failure and electrophysiological alternans in myocardial ischemia. The explanation of this phenomenon is still unclear. We attempted to investigate the cellular mechanisms of alternans by measuring intracellular free calcium concentration [( Ca2+]i) with the photoprotein aequorin in isolated ferret papillary muscles. Tension and length were also recorded simultaneously. Transient mechanical alternans lasting five to 20 contractions could be reliably induced in this preparation by following a 30-second rest period with stimulation at a fast rate (2-4 Hz). Production of sustained mechanical alternans, which lasted longer than 20 contractions and could persist for several hundred contractions, required additional interventions, consisting of a lower temperature (25 degrees C), a lower external calcium concentration (1 mM), and a lower pH (6.91) than control conditions (0.33-0.5 Hz, 30 degrees C, 2 mM Ca2+, pH 7.36). Transient mechanical alternans was associated with transient in-phase alternation of aequorin light and, hence, [Ca2+]i. Sustained mechanical alternans was associated with sustained in-phase alternation of aequorin light as well as incomplete relaxation of tension. However, when muscles were switched from isometric to unloaded isotonic contraction, relaxation between stimuli was complete but contraction and the aequorin light signal continued to alternate. The addition of 10 mM caffeine or 10 microns ryanodine abolished transient and sustained mechanical alternans and also abolished the associated alternation of aequorin light. Commensurate with the action of ryanodine, which allows the sarcoplasmic reticulum to reaccumulate calcium to a limited extent after a period of rapid stimulation, sustained mechanical alternans sometimes reappeared in an attenuated form 30 to 50 contractions after the addition of ryanodine. These results demonstrate that incomplete muscle relaxation between beats need not be present for alternans to occur, and support the hypothesis that alternans is caused by intracellular calcium cycling involving the sarcoplasmic reticulum. PMID- 2306801 TI - Effects of intracellular acidosis on [Ca2+]i transients, transsarcolemmal Ca2+ fluxes, and contraction in ventricular myocytes. AB - We examined the effects of intracellular acidosis produced by washout of NH4Cl on [Ca2+]i transients (indo-1 fluorescence), cell contraction (video motion detector), and 45Ca and 24Na fluxes in cultured chick embryo ventricular myocytes. Exposure of cells to 10 mM NH4Cl produced intracellular alkalosis (pH 7.6), and subsequent washout resulted in a transient acidosis (pH 6.5). Exposure to 10 mM NH4Cl slightly decreased [Ca2+]i transients but increased the amplitude of cell contraction. Subsequent washout of NH4Cl initially increased diastolic [Ca2+]i and decreased the peak positive and negative d[Ca2+]i/dt, while the amplitude of cell contraction was markedly decreased. Subsequently, peak systolic [Ca2+]i increased with partial recovery of contraction. A similar increase in [Ca2+]i and decrease in contraction after washout of NH4Cl was observed in single paced adult guinea pig ventricular cells. Acidosis decreased 45Ca uptake by sarcoplasmic reticulum vesicles isolated from chick embryo ventricle. However, the [Ca2+]i increase caused by intracellular acidosis was also observed in the presence of 10 mM caffeine, suggesting that altered sarcoplasmic reticulum handling of calcium is not the only mechanism involved. Intracellular acidosis only slightly increased total 24Na uptake under these conditions, an effect resulting from the combination of a stimulation of amiloride-sensitive sodium influx (Na(+)-H+ exchange) and inhibition of sodium influx via Na(+)-Ca2+ exchange, manifested by a significant decrease in 45Ca efflux. Further support for a lack of involvement of an increased [Na+]i in the observed increase in [Ca2+]i during acidosis was low-sodium, nominal 0-calcium extracellular solution, an experimental condition that minimizes the possible effects of Na(+)-H+ exchange and Na(+)-Ca2+ exchange. We conclude that the [Ca2+]i increase caused by intracellular acidosis in cultured ventricular cells is primarily due to changes in [Ca2+]i buffering and [Ca2+]i extrusion, rather than to an increase in transsarcolemmal calcium influx. Intracellular acidosis also markedly decreases the sensitivity of the contractile elements to [Ca2+]i in cultured chick embryonic and adult guinea pig ventricular myocytes. PMID- 2306802 TI - Mechanisms underlying the development of ventricular fibrillation during early myocardial ischemia. AB - The mechanisms underlying the development of ventricular fibrillation (VF) during early myocardial ischemia were assessed by use of a computerized three dimensional mapping system capable of recording simultaneously from 232 intramural recording sites throughout the entire feline heart in vivo. Occlusion of the proximal left anterior descending coronary artery led to ventricular tachycardia (VT), which degenerated to VF in 1-5 minutes in four of 15 animals. Normal sinus beats immediately preceding the initiation of VT leading to VF demonstrated delayed activation (total activation time 133 +/- 14 msec), which was not significantly different from the activation time for normal sinus beats immediately preceding nonsustained VT (149 +/- 7 msec). Most of the conduction delay occurred in the subendocardial and midmyocardial regions in both groups. Initiation of VT leading to VF occurred by intramural reentry in three of the four cases. In one case, a mechanism responsible for the initiation of VT could not be assigned. The coupling interval of the initiating beats of VT ultimately leading to VF (210 +/- 15 msec) did not differ from that of nonsustained VT. Maintenance of the VT that led to VF was due primarily to intramural reentry (84% of cases) involving multiple activation sites in and around the border region of the ischemic zone. Nonreentrant mechanisms, arising in the subendocardium and subepicardium, also contributed to the maintenance of VT before development of VT. The transition from VT to VF was due exclusively to intramural reentry with initiation of the reentrant beats in the subendocardium and, occasionally, the subepicardium. Acceleration of the tachycardia by intramural reentry, along with very rapid and inhomogeneous recovery of excitability (as low as 50-60 msec), led to increased functional block and conduction delay. As a result, the total activation time for a given beat exceeded the coupling interval for that beat and led to the multiple reentrant circuits and multiple simultaneous activations characteristic of VF. Thus, the initiation and maintenance of VT leading to VF during early ischemia is due to intramural reentry, although nonreentrant mechanisms also contribute. However, the development of VF is due to continued intramural reentry and rapid recovery of excitability. PMID- 2306803 TI - Attenuation of vasopressin-mediated coronary constriction and myocardial depression in the hypoxic heart. AB - To investigate the ability of arginine vasopressin (AVP) to compete with metabolic vasodilatory factors in the coronary circulation, we examined the coronary vascular and myocardial effects of AVP in isolated working rat hearts during normoxic and hypoxic perfusion. In normoxic hearts, AVP treatment (777 +/- 67 pg/ml) reduced coronary flow by 38.4 +/- 2.6%. Myocardial function was also significantly decreased by AVP whereas efficiency significantly increased. In contrast, the same dose of AVP administered to hypoxic hearts resulted in substantially smaller effects on coronary flow (-11.5 +/- 2.8%), myocardial function, and efficiency. In hearts treated first with AVP and then with hypoxia, the greater degree of coronary vasodilation compared with that observed in hearts treated with hypoxia alone also indicated an antagonizing effect of hypoxia on AVP-mediated coronary constriction. It was also noted that the hypoxia treatment alone resulted in reductions of O2 supply and consumption identical to those produced by AVP treatment during normoxia. However, hypoxia was associated with a significantly greater effect on myocardial function and, in contrast to the effect of AVP, a marked reduction in efficiency. The rate of lactate release was greater during hypoxia alone (2.07 +/- 0.08 mumol/min) than with AVP treatment during normoxia (0.76 +/- 0.05 mumol/min). These results indicate that the effect of AVP on the coronary vessels, as well as its effect on the myocardium, is significantly attenuated during hypoxia. In addition, AVP-constricted vessels appear to retain considerable vasodilatory reserve despite evidence of ischemic conditions. Thus, although the effects of AVP resemble ischemia, the increased efficiency and the relatively small effect of AVP on contractile function, as well as the preserved vasodilatory reserve, suggest otherwise. A physiological explanation for these observations is proposed wherein the constricting effects of AVP modulate the effects of autoregulatory factors such that blood flow requirements are minimized while allowing preservation of adequate blood flow for vital tissue function. PMID- 2306804 TI - Role of oxygen-derived free radicals in acute angiotensin II--induced hypertensive vascular disease in the rat. AB - Severe experimental hypertension is associated with vascular hyperpermeability and cellular damage in small arteries and arterioles in rats. Oxygen-derived free radical production is also associated with increased vascular permeability and cellular injury in a variety of conditions, including ischemia-reperfusion and inflammation. To determine if free radicals play a role in the pathogenesis of hypertensive vascular disease, the free radical scavengers superoxide dismutase (SOD), catalase, SOD and catalase, and dimethyl sulfoxide (DMSO) were given to rats made acutely hypertensive with angiotensin II infusions. Untreated hypertensive and normotensive control animals were used for comparison. The effects of scavenger treatment were assessed by in vivo observations of intestinal small arteries by use of stereomicroscopy and videotape and light and transmission electron microscopy to identify and quantitate vascular lesions, and tracer particle injections to determine permeability changes. In vivo observations revealed that scavenger treatment did not alter vascular constriction patterns, vessel caliber, or blood pressures. Electron microscopy of arteries from untreated hypertensive rats showed more severe and more extensive endothelial and smooth muscle lesions, increased tracer particle penetration, and greater fibrin deposition than that found in scavenger-treated hypertensive groups. Quantitation of vascular lesions showed approximately equal reductions in smooth muscle necrosis (p less than 0.01) and fibrin deposition (p less than 0.05) in arteries from each of the scavenger-treated hypertensive groups. The results indicate that the free radical scavengers SOD, catalase, SOD-catalase, and DMSO inhibit (but do not prevent) vascular hyperpermeability and cellular damage during acute, angiotensin II--induced hypertension. These findings suggest that free radicals play a role in the pathogenesis of hypertensive vascular disease, probably by exacerbating the vascular changes initially triggered by an acute elevation in blood pressure. PMID- 2306805 TI - Dobutamine potentiates amrinone's beneficial effects in moderate but not in advanced heart failure. 31P-MRS in isolated hamster hearts. AB - There is controversy as to whether potent inotropic agents are beneficial or detrimental in moderate to severe heart failure. Accordingly, we studied the effects of amrinone, amrinone plus dobutamine, and dobutamine alone on mechanical performance, myocardial oxygen consumption, and high energy phosphate metabolism in different stages of congestive heart failure in the cardiomyopathic Syrian hamster. In hearts with moderate heart failure, administration of amrinone, amrinone plus dobutamine, and dobutamine alone increased developed pressure significantly, whereas the phosphorylation potential increased significantly only with amrinone and amrinone plus dobutamine. In hearts with advanced heart failure, administration of amrinone and amrinone plus dobutamine increased developed pressure significantly, whereas dobutamine alone had no effect. The phosphorylation potential improved significantly only with amrinone. Thus, amrinone improved mechanical performance and mitochondrial activity in both heart failure states. Dobutamine potentiated amrinone's beneficial effects in moderate heart failure, but negated the positive inotropic effect of amrinone in advanced heart failure. Therefore, hearts responded differently to potent inotropic agents depending on the severity of heart failure. PMID- 2306806 TI - Myocardial hibernation in the ischemic neonatal heart. AB - We explored the effects of sustained low-flow ischemia on function and metabolism in isolated neonatal hearts. The hearts were extracted from 21 piglets (1-12 days old) and set up as modified Langendorff preparations beating isometrically. They were perfused with red blood cell-enhanced buffer at controlled rates of coronary flow. Mechanical measurements, O2 usage, and substrate oxidation were determined simultaneously at 30-minute intervals for 2 hours. In control hearts, coronary flow was maintained at 1.8 ml/min/g. There was no significant change in mechanical function, diastolic compliance, or O2 or substrate metabolism after 2 hours. In the ischemia group, coronary flow was reduced to 0.2 ml/min/g and sustained for 2 hours. With the onset of ischemia, mechanical function promptly fell to 20% of control. Although O2 delivery was reduced to 11%, O2 extraction doubled so that myocardial O2 consumption was 22% of control, matching mechanical function. Glucose oxidation fell from 37 to 12 nmol/min/g, and lactate release appeared. These measures and ventricular compliance remained constant for the full 2 hours. Concentrations of glycogen and creatine phosphate did not differ from the control group; ATP was 76% of controls. These studies indicate that when myocardial O2 supply is limited, mechanical function rapidly diminishes, largely preserving critical energy stores and preventing irreversible myocellular injury. Although the signal remains to be determined, the strategy is similar to that employed by hibernating species to survive extended periods of O2 deprivation. PMID- 2306807 TI - The hyperthyroid heart. An analysis of systolic and diastolic properties in single rat ventricular myocytes. AB - Single ventricular myocytes were isolated by collagenase digestion from the hearts of 6-8-month-old male Wistar rats in either the control (euthyroid) state or after 7 days of daily injection of 0.64 mg/kg thyroxine (hyperthyroid). Myocytes were field-stimulated from slack length, and contraction was measured with an inverted microscope-photodiode array-computer apparatus. The effect of pacing rate and ouabain administration on systolic and diastolic function was examined. Single myocytes isolated from hyperthyroid hearts maintain the properties of bulk muscle, because maximal twitch velocity is augmented 98% and the time course of contraction as measured by the time to peak shortening, relaxation time, or contraction duration is abbreviated 39%. Spontaneous sarcoplasmic reticulum calcium release, as measured by the occurrence of contractile waves, is increased in the hyperthyroid myocytes. This increased frequency of spontaneous sarcoplasmic reticulum calcium release is most marked under conditions known to be associated with high intracellular calcium, such as low pacing rates or digitalis glycoside administration. It can account for the hypoperformance of the hyperthyroid myocytes noted under these conditions because it is associated with depletion of sarcoplasmic reticulum calcium stores and diminution of subsequent twitch amplitude. These observations may help explain, in part, the cellular basis of the altered cardiac performance in the hyperthyroid state. PMID- 2306808 TI - Effect of thromboxane A2/endoperoxide antagonist SQ29548 on the contractile response to acetylcholine in newborn piglet cerebral arteries. AB - Previous studies have shown that cholinergic stimulation results in a prostanoid dependent cerebral vasoconstriction in piglets. The present study specifically investigated the contribution of thromboxane A2 (TXA2)/prostaglandin endoperoxide and prostaglandin F2 alpha (PGF2 alpha) to the cerebral vascular response to exogenous acetylcholine (ACh). Effects of TXA2/prostaglandin endoperoxide receptor antagonist SQ29548 on responsiveness of pial arterioles to ACh (10(-7) and 10(-4) M), PGF2 alpha (10(-7)-10(-5) M), TXA2 mimetic 9,11-methanoepoxy prostaglandin H2 (U46619, 5 and 10 ng/ml), and norepinephrine (10(-6)-10(-4) M) were studied by use of a closed cranial window in 37 anesthetized mechanically ventilated newborn piglets. Pial arteriolar diameter was measured by intravital microscopy. Topical application of exogenous PGF2 alpha and U46619 resulted in dose-dependent cerebral vasoconstriction, and the dose-response curve for each agonist was shifted to the right by the increasing concentrations of SQ29548 (10( 6)-10(-8) M). Topical application of high concentration of ACh (10(-4) M) caused a transient 34 +/- 4% decrease in pial arteriolar diameter from 98 +/- 6 to 65 +/ 5 microns (p less than 0.05). This constriction was attenuated (16 +/- 3%) in the presence of 10(-8) M SQ29548 and abolished with 10(-6) or 10(-4) M SQ29548. SQ29548 (10(-6) M) was without effect on the vasoconstrictor response to exogenous norepinephrine. Low concentration of ACh (10(-7) M) had no consistent effect on pial arterioles in the absence or presence of TXA2/prostaglandin endoperoxide-receptor blockade. The data suggest that vascular prostaglandin/endoperoxide receptors mediate cerebral vasoconstriction upon muscarinic-receptor stimulation. PMID- 2306809 TI - Isoform distribution and tissue contents of contractile and cytoskeletal proteins in hypertrophied smooth muscle from rat portal vein. AB - Growth of the smooth muscle in the rat portal vein was initiated by an increased transmural pressure. After 7 days, the cross-sectional area of the vessel wall and the maximal active force of the longitudinal muscle layer had increased twofold. Electron microscopy showed that the cell cross-sectional area was increased, suggesting cellular hypertrophy. Increased amounts of intermediate (10 nm) filaments were observed in the hypertrophied cells. The hypertrophied vessels had decreased DNA content per unit wet weight compared with the control vessels (hypertrophied, 1.5 +/- 0.1; control, 1.9 +/- 0.1 micrograms/mg; p less than 0.01). Protein composition was studied with electrophoretic methods. Compared with control preparations the hypertrophied veins had similar myosin and actin contents per unit wet weight (myosin: hypertrophied, 4.4 +/- 0.8; control, 5.9 +/ 0.9; actin: hypertrophied 12.2 +/- 0.6; control, 11.8 +/- 1.0 mg/g). Two different forms of the myosin heavy chain were detected with 5% sodium dodecyl sulfate-polyacrylamide gels. The proportion of the lower molecular weight heavy chain relative to total heavy chain content was about 30% and similar in both preparations. The relation filamin/myosin was increased in the hypertrophied vessels. Pyrophosphate gel electrophoresis revealed two protein bands, with an increase in the slower migrating band in the hypertrophied vessels possibly reflecting an increase in filamin content in the extracts. In the control portal vein alpha-actin is the dominating isoform constituting about 55% of total actin. In hypertrophied vessels, alpha-actin decreased (by 15%) and gamma-actin increased (by 20%). The portal vein contained desmin and vimentin in a ratio of about 6:1. The hypertrophied vessels showed a marked increase in the amount of these proteins (desmin/actin: hypertrophied, 0.32; control, 0.14). In conclusion, during pressure-induced growth of the portal vein, contractile protein contents increase in proportion to the increase in weight. A change in isoforms of actin occurs but no evidence for a change in myosin isoforms was found. The structural proteins increase relative to tissue weight, possibly associated with the increased number of intermediate filaments demonstrated with electron microscopy. PMID- 2306810 TI - Coronary arteriolar myogenic response is independent of endothelium. AB - The purpose of this study was to investigate if myogenic responses of isolated coronary arterioles were dependent on an intact, functional endothelium. Arterioles were located in situ by intracoronary perfusion with india ink-gelatin solution and then dissected and cannulated at both ends with glass micropipettes. Intraluminal pressure was initially set at 60 cm H2O; then the pressure was altered in steps of 20 cm H2O over a range of 20-140 cm H2O. Arterioles developed spontaneous tone and exhibited a significant myogenic response in physiological saline solution (36 degrees -37 degrees C). Arteriolar dilation and constriction were observed at lower (20-60 cm H2O) and higher (60-140 cm H2O) pressures, respectively. The presence of a functional and automatically intact endothelium was confirmed by relaxation to the endothelium-dependent vasodilator bradykinin and by transmission electron microscopy, respectively. After mechanical denudation of the endothelium with a specially designed abrasive micropipette, spontaneous tone and myogenic responses were preserved. Denudation of the endothelium was verified functionally (no response to bradykinin) and with transmission electron microscopy. Moreover, the mechanical denudation technique did not deleteriously affect smooth muscle because vasoconstrictor and vasodilator responses to nonendothelial-dependent drugs were the same before and after denudation. In summary, the present study demonstrates that pressure dependent responses occur in isolated coronary arterioles and that this response is not dependent on the endothelium. Therefore, pressure-induced changes in coronary arteriolar tone are a true myogenic response in that they originate from smooth muscle. PMID- 2306811 TI - Accelerated thrombolysis and reperfusion in a canine model of myocardial infarction by liposomal encapsulation of streptokinase. AB - The aim of thrombolytic therapy for acute myocardial infarction with plasminogen activators such as streptokinase is to lyse the coronary thrombus and reestablish blood flow as quickly as possible so that heart tissue loss is minimized and mortality rates are improved. Streptokinase has been encapsulated in large unilamellar phospholipid vesicles and tested in an animal model of acute myocardial infarction. The time required to restore vessel patency has been reduced more than 50% when compared with findings for free streptokinase. The total dosage of streptokinase required was lower, and smaller remnant thrombi were observed with the encapsulated agent. Results from this initial unoptimized study may have significant implications for further reduction in mortality from heart attacks by therapy with plasminogen activators. PMID- 2306812 TI - Experimental balloon valvuloplasty of fibrotic and calcific mitral valves. AB - This study evaluated the mechanism of valvular area expansion during single- and double-balloon valvuloplasty in fibrotic and calcific mitral valves. Special interest was focused on the morphological features of the valves treated. Mitral valves that appeared unsuitable for commissurotomy were excised in toto at the time of mitral valve replacement in 15 patients. The excised valves were mounted in a fluid-filled chamber with a window for photographic evaluation. The chamber was perfused continuously to ensure maximal valvular opening. The valve was photographed, and the orifice area was measured before and after balloon expansion. In addition, the specimens were examined macroscopically and radiographically with regard to calcium content and degree and localization of fibrosis. These data were correlated with splitting of commissures and with rupture of leaflets. Nine valves were fibrotic, and six were calcific. Dilatation was performed first with a single-balloon catheter (diameter, 2 cm) and then with a double-balloon catheter (diameter, 2 and 1.5 cm). After dilatation with one balloon, the average mitral valve area increased from 0.79 to 1.09 cm2, and with two balloons, average area increased to 1.59 cm2. The single-balloon technique caused commissural splitting in nine valves, stretching in three, partial leaflet rupture in one, and no change in two. After the double-balloon technique, commissural splitting occurred in 12 valves and three leaflets were ruptured where severe fibrosis and calcification were mainly located within the commissures. As a rule, after dilatation with the single-balloon technique, the remaining stenosis was still severe, and after dilatation with the double-balloon technique, the remaining stenosis was moderate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306813 TI - Mechanism of cocaine-induced myocardial depression in dogs. AB - Cocaine causes pronounced depression of left ventricular function in conscious dogs immediately after intravenous administration. To examine this effect, 14 mongrel dogs were anesthetized with pentobarbital sodium (32 mg/kg) and instrumented with arterial and venous catheters and a Doppler blood flow transducer on the left circumflex coronary artery. Two weeks later, heart rate, blood pressure, coronary blood flow, and regional left ventricular ejection fraction (by two-dimensional echocardiography) were measured before and 1, 2, 5, and 10 minutes after cocaine (4 mg/kg i.v.), while the animals were fully conscious. Heart rate, blood pressure, and coronary blood flow were increased significantly at each time after cocaine. Regional ejection fraction, however, was depressed by 50 +/- 7%, 35 +/- 4%, and 21 +/- 4% at 1, 2, and 5 minutes after cocaine treatment, respectively. Ten minutes after cocaine treatment, regional ejection fraction had recovered to a level not significantly different from baseline. Because the observed myocardial depression after cocaine was accompanied by a large increase in the rate-pressure product, and presumably, myocardial oxygen consumption, this depression could have been secondary to increased myocardial oxygen demand not appropriately matched by an increase in coronary blood flow. To minimize the effects of cocaine on myocardial oxygen demand, a subset of six dogs received cocaine (4 mg/kg i.v.) while sedated with pentobarbital (25 mg/kg). In these dogs, cocaine did not significantly alter heart rate or blood pressure; however, regional ejection fraction was significantly depressed by 44 +/- 5% and 36 +/- 6% at 1 and 2 minutes after cocaine treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306814 TI - Characterization of acute experimental left ventricular thrombi with quantitative backscatter imaging. AB - Two-dimensional echocardiography is an excellent technique for detecting left ventricular thrombi, however, acute clot is sometimes difficult to differentiate from adjacent myocardium and intracavitary signals. We hypothesized that quantitative assessment of the acoustic properties of acute left ventricular thrombi using a quantitative backscatter imaging system would permit the differentiation of thrombus from adjacent myocardium and intracavitary echoes. Acute, experimental left ventricular thrombi in seven dogs were evaluated with a quantitative backscatter imaging system that allowed the measurement of relative integrated backscatter and cyclic (i.e., diastolic minus systolic) variation in integrated backscatter. Coronary ligation abolished the cyclic variation in relative backscatter that occurred in normal myocardium. The end-diastolic relative backscatter in the thrombus (16.9 +/- 1.3 dB) was significantly higher than in apical myocardium (13.2 +/- 0.6 dB, p less than 0.05). There was no significant difference in the cyclic variation in relative backscatter among thrombus, ischemic myocardium, or intracavitary blood. Thus, the quantitative assessment of the acoustic properties of left ventricular thrombi can be useful in their detection and in the differentiation from myocardium and intracavitary signals. PMID- 2306815 TI - Microcinephotography of the developing heart in neural crest-ablated chick embryos. AB - Microcinephotography was used to study heart development in a neural crest model of heart defects, that is, persistent truncus arteriosus, interrupted aortic arch, double outlet right ventricle, or single ventricle and tricuspid valve anomalies. These defects were created in chick embryos by ablation of premigratory neural crest destined for the aorticopulmonary and truncal septa, as well as the third and fourth aortic arch arteries. When embryogenesis reached the looped cardiac tube stage of development (Hamburger-Hamilton stage 18), 19 experimental and 15 control embryos were filmed at 100 frames per second under controlled environmental conditions. Analysis of the microcinephotography films showed the following significant distinguishing characteristics of the developing heart in the experimental embryos: altered conotruncal shape in 100%, depressed contractility and dilation of the primitive ventricle in 84%, decreased emptying of the bulbus cordis in 79%, incompetent truncal cushions in 68%, incomplete looping of the cardiac tube in 58%, and fourth right aortic arch artery without blood flow and third right aortic arch artery with increased flow in 53%. These abnormal characteristics suggested that there were functional and morphological changes in the developing heart of experimental embryos before the time when the predicted structural heart defects would be apparent. It is proposed that the primitive ventricle might attempt to compensate for depressed contractility by ventricular dilation. The incompetent truncal cushions could be secondary to the depressed contractility or secondary to the neural crest ablation that is known to cause persistent truncus arteriosus, an interrupted aortic arch, or both. The absence of blood flow in the right fourth aortic arch artery that will become the definitive aorta correlates with the expected incidence of interrupted aortic arches in this neural crest-ablation model of heart defects. It is speculated that the incomplete looping of the cardiac tube might hinder normal developmental alignment of the outflow and inflow tracts, producing a spectrum of lesions of maldevelopment of the tricuspid valve and dextroposition of the aorta. PMID- 2306816 TI - The dependence of the time constant of left ventricular isovolumic relaxation (tau) on pericardial pressure. AB - The purpose of this study was to investigate the dependence of tau, the time constant of left ventricular (LV) isovolumic relaxation, on pericardial pressure and to compare values of tau as determined by the methods of previous investigators and by a standard exponential curve fit. All of the more recent methods involve an additional parameter--the pressure to which the exponential relaxation finally declines (PB, the pressure intercept in the method of Craig and Murgo and the asymptote in the exponential fits). An additional purpose of the study was to determine the relation of these parameters to pericardial pressure. In eight closed-chest anesthetized dogs, tau was calculated from intracavitary (Plv) and transmural LV pressure (Plv = Plv-Pper) by each method as pericardial (Pper) and LV end-diastolic pressure were changed by pericardial infusion and intravenous volume loading. The time constant determined by the method of Weiss et al was dependent on pericardial pressure; the time constants determined by the other methods were not. PB and the asymptotes were found to be similar and to increase almost equally with pericardial pressure. When pericardial pressure was zero, these values were approximately -20 mm Hg. Thus, both these parameters seem to indicate the same baseline pressure, a pressure that increases pari passu with pericardial pressure. Reported changes in the value of tau calculated from intracavitary LV pressure by the method of Weiss et al may reflect factors other than changes in LV diastolic function. PMID- 2306817 TI - Eosinophils from hypereosinophilic patients damage endocardium of isolated feline heart muscle preparations. AB - Persistent eosinophilia in humans is often associated with endocardial damage to the heart, but a causal relation has not been established. We investigated the effect of eosinophils and eosinophil supernatants obtained from eight hypereosinophilic patients on the contractile performance and endocardial morphology of isolated, electrically stimulated cat papillary muscle preparations (n = 16). All these eosinophil suspensions contained high proportions of "hypodense" or "activated" cells. Eosinophils (5-15 x 10(6) ml organ bath) or eosinophil culture supernatants (prepared by overnight incubation at 37 degrees C) when added to papillary muscles produced acute changes in contractile behavior of these muscles identical to the previously reported effects of selective endocardial damage: a reduction in time to peak isometric twitch tension causing a reduction in peak isometric tension but with no significant reduction in rate of tension development or in maximum unloaded shortening velocity. All of these muscle preparations showed severely damaged endocardium at scanning electron microscopy. Addition of eosinophils from hypereosinophilic patients to muscles with selectively damaged endocardium (by previous transient [1-second] exposure to 1% Triton X-100) produced no further change in contractile performance. No significant change in contractile performance or endocardial morphology of papillary muscles (n = 16) was observed after addition of eosinophils (7.5-10 x 10(6] or neutrophils (8-15 x 10(6] from normal subjects or of cell-free culture medium. Thus, activated human eosinophils produce specific morphological and functional changes suggestive of specific damage to endocardium of isolated feline cardiac muscle. PMID- 2306818 TI - Aurintricarboxylic acid in a canine model of coronary artery thrombosis. AB - Platelet thrombus formation occurs at sites of severe arterial narrowing where shear stress is elevated. Shear stress appears to induce platelet aggregation in vitro by means of initiation of von Willebrand factor binding to platelet glycoprotein Ib. Recent in vitro studies have demonstrated that aurintricarboxylic acid can inhibit shear stress-induced platelet aggregation. This effect is mediated by aurintricarboxylic acid binding to von Willebrand factor; this binding results in inhibition of von Willebrand factor interaction with glycoprotein Ib. In this study, we examined the effect of aurintricarboxylic acid on platelet-dependent cyclic flow reductions (CFRs) in a canine coronary stenosis model. In dose-response experiments, six animals received 4 mg/kg aurintricarboxylic acid by bolus infusion, followed by 1 mg/kg every 10 minutes. Total inhibition of CFRs was observed in all animals after 6.7 mg/kg aurintricarboxylic acid; CFRs could not be reinitiated by the thromboxane A2 analogue U46619. Continuous infusion of epinephrine (0.4 micrograms/kg/min) caused CFRs to return; however, 3.7 mg/kg additional aurintricarboxylic acid again induced total inhibition of CFRs. In addition, five animals received a bolus infusion of 10 mg/kg aurintricarboxylic acid, which caused total inhibition of CFRs. The average area of stenosis in the constricted vessels was 83%, and shear stress at the site of constriction averaged 350 dynes/cm2. Aurintricarboxylic acid did not alter hemodynamics, thrombin time, platelet count, or ADP/epinephrine-induced platelet aggregation. These data indicate that platelet glycoprotein Ib-von Willebrand factor interactions are important during coronary occlusion and that aurintricarboxylic acid can inhibit coronary thrombosis associated with coronary constriction. PMID- 2306819 TI - Ambulant myocardial ischemia and its prognostic implications. PMID- 2306820 TI - Targeted drug therapy. PMID- 2306821 TI - Atrial flutter. New directions in management and mechanism. PMID- 2306822 TI - An artery has many masters. PMID- 2306823 TI - A model of myocarditis in humans. PMID- 2306824 TI - Prognostic importance of dipyridamole-echocardiography test. PMID- 2306825 TI - Simultaneous aortic, jugular bulb, and right atrial pressures during cardiopulmonary resuscitation in humans. PMID- 2306826 TI - Silent ischemia during daily life is an independent predictor of mortality in stable angina. AB - We prospectively examined the prognostic significance of silent myocardial ischemia detected by ambulatory electrocardiogram (ECG) monitoring during daily life in 107 patients with long-term stable angina who were symptomatically controlled on conventional antianginal agents. Forty-six patients (group 1) demonstrated one or more episodes (87% silent) of myocardial ischemia; the remaining 61 patients (group 2) had no ischemic ST segment changes. During the mean follow-up period of 23 +/- 8 months, 11 cardiac deaths (five sudden and six nonsudden) occurred in group 1, and five cardiac deaths (all nonsudden) occurred in group 2. Kaplan-Meier survival analysis between the groups confirmed that patients with silent ischemia (group 1) had worse prognoses during the follow-up period (p = 0.023). Although the higher incidence of hypertension, smoking, hypercholesterolemia, and diabetes in our patients might reflect a more sickly population of stable angina patients, the multivariate Cox's hazard function analysis of these and other variables including Q waves on ECG, exercise parameters, and ambulatory ECG findings revealed presence of silent ischemia during daily life as the most powerful and independent predictor of cardiac mortality (p = 0.01). These data indicate that, in such patients with stable angina, silent myocardial ischemia occurs frequently during treatment with conventional antianginal drugs and identifies a subset of patients who are at high risk of cardiac death. PMID- 2306827 TI - Transcoronary chemical ablation of atrioventricular conduction. AB - In seven patients with symptomatic atrial fibrillation and uncontrollable ventricular rates, selective catheterization of the atrioventricular (AV) nodal artery was performed to chemically destroy the AV node. Ethanol at a concentration of 96% and a dose of 0.5-2 ml was used after selective catheterization of the AV nodal artery had demonstrated temporary AV block after the administration of isotonic iced saline. Complete AV block was produced in five patients and AV conduction was sufficiently modified to control symptoms in the remaining two patients. A minimal enzyme rise occurred in six patients. A severe complication in the remaining patient occurred when, after 2 ml ethanol in the AV nodal artery, occlusion developed in the midright coronary artery that led to an inferior wall myocardial infarction. It is concluded that the AV nodal artery can be selectively catheterized using presently available angioplasty techniques. Ethanol can be used to destroy the AV node and block AV conduction. PMID- 2306828 TI - Catheter ablation of the atrial myocardium in human type I atrial flutter. AB - To avoid atrioventricular node-His bundle ablation, catheter ablation of the atrial myocardium was attempted in eight patients with drug refractory type I atrial flutter. In seven of eight patients, a zone of prolongation and fragmentation of the endocardial electrogram was found in the low posterior part of the right atrium. Entrainment of the atrial flutter by high right atrial pacing was accompanied by local recording of second-degree regional block in several atrial sectors but never in the low septal area. We, therefore, hypothesized that the latter represented the critical slow conduction zone of the reentrant flutter circuit. One or two cathodal DC shocks were locally delivered without immediate or late complications. One single ablation attempt was performed in five patients, whereas three patients underwent a second attempt because of early flutter recurrence. Patients were initially discharged without (and after a second session with) antiarrhythmic drugs. After a mean follow-up of 15.5 months (range, 10-23 months), five patients are free of arrhythmias without antiarrhythmic drug therapy. Two patients did not experience atrial arrhythmias while on a drug regimen that was previously found to be ineffective, and a third patient had flutter recurrences. This study suggests that patients with type I atrial flutter referred for atrioventricular node-His bundle ablation may be successfully managed by delivering the ablative shock directly on the atrial arrhythmia substrate. PMID- 2306829 TI - Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy. AB - Dilator reserve of the coronary microvasculature is diminished in patients with dilated cardiomyopathy. Although increased extravascular compressive forces, tachycardia, and increased myocardial mass can explain some impairment, recent evidence suggests the possibility of intrinsic microvascular disease. We tested the hypothesis that impairment of endothelium-dependent dilation of the microvasculature could be a contributing mechanism. We infused the endothelium dependent dilator acetylcholine (Ach) (10(-8) to 10(-6) M) and the smooth muscle vasodilator adenosine (AD) (10(-6) to 10(-4) M) into the left anterior descending coronary artery in eight patients with dilated cardiomyopathy (mean ejection fraction, 28%) and seven controls (atypical chest pain). Small vessel resistance was assessed by measuring coronary blood flow (CBF) at constant arterial pressure with a Doppler velocity catheter (corrected for cross-sectional area by angiography). With Ach, control patients increased CBF 232 +/- 40% (mean +/- SEM), whereas CBF did not significantly change in cardiomyopathy patients (41 +/- 24%) (p less than 0.0001, control vs. cardiomyopathy). With AD, control patients increased CBF 422 +/- 56% and cardiomyopathy patients increased CBF 268 +/- 43% (p = 0.13). An index of the proportion of coronary flow reserve attributable to endothelium-dependent vasodilation was obtained by standardizing each patient's Ach dose response to his maximal AD flow response. In seven control patients receiving both Ach and AD, 56 +/- 9% of the maximal AD flow response was attained with the endothelium-dependent vasodilator Ach, whereas in seven cardiomyopathy patients receiving both Ach and AD, only 23 +/- 14% of the maximal AD response was attained (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306830 TI - Prognostic significance of the electrocardiogram after Q wave myocardial infarction. The Framingham Study. AB - The prognostic value of abnormalities on the electrocardiogram (ECG) present 1 year after initial myocardial infarction (MI) is examined in relation to reinfarction and coronary death throughout 32 years (mean, 10.1 years) of follow up in the Framingham Heart Study. Resting 12-lead ECGs were available in 251 survivors (190 men and 61 women) of clinically recognized Q wave MI. The ECG reverted to normal in 31 (12.4%) cases and was abnormal but without Q waves in 37 (14.7%). Q waves persisted without other significant abnormalities in 108 (43.0%) and with other abnormalities in 75 (29.9%) cases. Electrocardiographic abnormalities at follow-up were more common in women and in those persons whose initial MI was anterior as compared with inferior. Nonspecific T wave, ST segment changes, and electrocardiographic left ventricular hypertrophy on the ECG before or after MI were powerful predictors (p less than 0.01) of coronary death. The relation of these residual post-MI electrocardiographic findings to reinfarction and coronary death was assessed by Cox regression analysis. The follow-up electrocardiographic status was unrelated to the risk of subsequent reinfarction. Subjects who lost Q wave evidence of MI but whose ECG continued to show evidence of repolarization abnormalities, left ventricular hypertrophy, or blocked intraventricular conduction were at a 3.5-fold increased risk (p less than 0.01) of coronary death as compared with those reverting to a normal ECG. Persons with a persistent Q wave MI accompanied by these abnormalities were at a 2.7-fold excess risk (p = 0.01) of coronary death as compared with those with a normalized ECG. These findings remained significant when considering age and standard coronary risk factors. The presence of other electrocardiographic abnormalities without persistent Q waves yields a worse prognosis than a Q wave persisting alone. The prognostic value of a follow-up ECG with abnormalities other than a persistent Q wave MI also remained after considering the effects of left ventricular hypertrophy and cardiac enlargement on x-ray, functional classification, and diuretic usage. Specific electrocardiographic abnormalities present before infarction, however, were potent indicators of long-term prognosis prognosis and diminished the importance of the follow-up ECG. Although survival after initial MI is improved only if the ECG reverts to normal, information on electrocardiographic abnormalities before MI can be especially useful in evaluating long-term risk. PMID- 2306831 TI - Frequency-dependent effects of quinidine on the ventricular action potential and QRS duration in humans. AB - We studied the frequency-dependent effects of quinidine on the right ventricular action potential and QRS duration in 10 patients (nine men and one woman; mean age, 57 +/- 14 years) undergoing electrophysiologic studies for clinical indications. The right ventricular monophasic action potential, electrocardiographic, and conventional intracardiac electrical signals from various sites were recorded at different pacing cycle lengths from 30 seconds to 1 minute before and after a 10-mg/kg i.v. quinidine infusion. We used the extrastimulus technique to determine the effects of quinidine on ventricular refractory periods at different pacing cycle lengths and on the abrupt changes of the action potential duration. The action potential duration progressively decreased as the ventricular pacing rate increased at baseline and after quinidine infusion. Quinidine significantly increased the action potential duration from that of control by 25 msec (p less than 0.02) at the relatively slow pacing cycle lengths of 600, 500, and 400 msec. Quinidine's effect on the action potential duration was attenuated at the pacing cycle length of 350 msec and became negligible at 300 msec. In contrast, quinidine progressively lengthened the QRS duration as the pacing rate increased (20, 18, 37, 46, and 34 msec at pacing cycle lengths of 600, 500, 400, 350, and 300 msec, respectively; p less than 0.05). There were no rate-dependent changes in the QRS duration during the control period. The relation between the ventricular refractory periods and the action potential duration at different pacing cycle lengths was also determined before and after quinidine infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306832 TI - Improving the predictive ability of the signal-averaged electrocardiogram with a linear logistic model incorporating clinical variables. AB - To improve the predictive accuracy of the signal-averaged electrocardiogram, we created a linear logistic model for predicting ventricular tachycardia during electrophysiologic testing. This signal-averaged electrocardiographic model was created from data obtained from 214 patients undergoing electrophysiologic testing (70 had ventricular tachycardia during electrophysiologic testing) by using stepwise logistic regression to rank eight clinical and nine signal averaged electrocardiographic variables. The best predictors were ejection fraction, history of infarction, ventricular ectopic pairs or nonsustained ventricular tachycardia on Holter monitoring, QRS duration after 25-Hz filtering, and root mean square voltage of the terminal 40 msec of the QRS complex after 40- and 80-Hz filtering. Cross validation (a statistical technique that can be used to accurately evaluate how a predictive model will perform on a prospective patient population) was used to validate the model. After cross validation, the model's sensitivity was 91% and specificity was 59% for predicting ventricular tachycardia during electrophysiologic testing. This model compared favorably with established 25-Hz late-potential criteria (QRS duration of more than 110 msec and root mean square voltage of less than 25 microV of the terminal 40 msec of the QRS complex; sensitivity, 64%; specificity, 85%) and with established 40-Hz late potential criteria (QRS duration of more than 114 msec or root mean square voltage of less than 20 microV of the terminal 40 msec of the QRS complex or duration of the low-amplitude signal less than 40 microV at the terminal QRS complex that is greater than 38 msec; sensitivity, 84%; specificity, 54%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306833 TI - Electrophysiological effects of adenosine in the transplanted human heart. Evidence of supersensitivity. AB - After cardiac transplantation, the denervated donor atria and ventricles demonstrate increased sensitivity to infusions of sympathomimetic amines. Recently, supersensitivity of the canine sinus and atrioventricular (AV) nodes to acetylcholine has also been demonstrated after parasympathetic denervation. Acetylcholine and the endogenous nucleoside adenosine exert similar electrophysiological effects in both the sinus and AV nodes, and share a common transduction process. We, therefore, hypothesized that after orthotopic cardiac transplantation, the donor (denervated) sinus node would demonstrate greater sensitivity to exogenous adenosine than the recipient (innervated) sinus node. The effects of incremental doses of intravenous adenosine (37-112 micrograms/kg) on changes in sinus cycle length (SCL) (delta SCLmax%), changes in PR interval (delta PRmax%), time to peak effect (sec), and duration of electrophysiological effects (sec) were prospectively measured in 28 orthotopic cardiac transplant patients and nine control subjects. The baseline SCL was 795 +/- 71 msec for the control subjects, 891 +/- 43 msec for the recipient atria, and 700 +/- 18 msec for the donor atria (p less than 0.05, donor vs. recipient). The delta SCLmax% for each dose of adenosine was similar in the innervated control and recipient atria. In contrast, the donor sinus node demonstrated a threefold to fourfold increased response to adenosine as compared with the recipient sinus node and a threefold to sixfold increased response as compared with control subjects. Similarly, the donor AV node demonstrated a threefold to fivefold increase in PR interval as compared with control subjects. The duration of sinus node slowing in the denervated atria was threefold to fivefold longer than in the recipient and control atria (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306834 TI - Serial measurement of integrated ultrasonic backscatter in human cardiac allografts for the recognition of acute rejection. AB - Cyclic variation of integrated ultrasonic backscatter (IB) was noninvasively measured in the septum and left ventricular posterior wall using a quantitative IB imaging system to assess the alterations in the acoustic properties of myocardium associated with acute cardiac allograft rejection. The study population consisted of 23 cardiac allograft recipients and 18 normal subjects. In each cardiac allograft recipient, one to eight (mean, four) IB studies were performed, each within 24 hours of right ventricular endomyocardial biopsy performed for rejection surveillance. The magnitude of the cyclic variation of IB in the posterior wall was 5.9 +/- 0.9 dB in normal subjects and 6.2 +/- 1.3 dB in the cardiac allograft recipients without previous or current histological evidence of acute rejection (n = 17, p = NS vs. normal subjects). The magnitude of cyclic variation of IB in the septum was 4.8 +/- 1.1 dB in normal subjects and 3.8 +/- 2.0 dB in the cardiac allograft recipients (n = 15, p = NS vs. normal subjects). A significant decrease in the septal IB measure was observed in cardiac allograft recipients with left ventricular hypertrophy (wall thickness of at least 13 mm) (2.6 +/- 1.7 dB, n = 8, p less than 0.05 vs. normal subjects). IB studies were done before and during moderate acute rejection in 11 recipients (14 episodes). During moderate acute cardiac rejection, the magnitude of the cyclic variation in IB decreased from 6.7 +/- 1.3 to 5.1 +/- 1.4 dB in the posterior wall (n = 14, p less than 0.05) and from 4.2 +/- 2.1 dB to 2.9 +/- 1.8 dB in the septum (n = 12, p less than 0.05). These data suggest 1) the magnitude of the cyclic variation in IB of the septum is different in cardiac allografts with cardiac hypertrophy and normal subjects, possibly reflecting regionally depressed myocardial contractile performance and 2) acute cardiac rejection in humans is accompanied by an alteration in the acoustic properties of the myocardium. This change is detectable by serial measurement of the magnitude of the cyclic variation in IB, both in the septum and in the posterior wall. PMID- 2306835 TI - Body surface mapping during percutaneous transluminal coronary angioplasty. QRS changes indicating regional myocardial conduction delay. AB - Using a radiotransparent electrode array, body surface maps (BSMs) were constructed based on simultaneous recordings from 62 leads on the entire thorax before, during, and after balloon inflation during percutaneous transluminal coronary angioplasty (PTCA). Twenty-five patients were studied, and 30 angioplasties were performed; 20 patients had one-vessel disease, and five patients had two-vessel disease. In total, 15 dilations in the left anterior descending artery (LAD), seven in the right coronary artery (RCA), and eight in the left circumflex artery (LCx) were studied. For each patient, the BSM and the QRS integral map before, during, and after the inflation was compared by subtraction of recordings "during-minus-before" inflation and "before-minus after" inflation. The subtraction was performed on the results of the QRS integral maps. The conclusions derived from the inspection of the BSMs and the difference maps show specific changes in the QRS complex during ischemia related to the corresponding ischemic segment in 21 of 25 patients in the three groups. An area of positive potentials remained present on the BSM during dilation, indicating a depolarization wave front. For the LAD group, positive potentials were seen on the anterior thorax and, for the RCA group, on the lower part of the thorax. By subtraction analysis, these changes were extracted and presented as difference maps. For the LCx group, the BSM revealed no changes in pattern but the difference map showed a difference vector pointing in a anteroposterior direction. A regional myocardial conduction delay was hypothesized as the most likely cause for the results. PMID- 2306837 TI - Do changes in pulmonary capillary wedge pressure adequately reflect myocardial ischemia during anesthesia? A correlative preoperative hemodynamic, electrocardiographic, and transesophageal echocardiographic study. AB - Pulmonary capillary wedge pressure (PCWP) is monitored during anesthesia in an attempt to detect changes in myocardial function in patients at risk of preoperative cardiac complications. Because the sensitivity with which preoperative PCWP monitoring indicates myocardial ischemia is uncertain, we monitored PCWP, 12-lead electrocardiogram, and left ventricular wall motion abnormalities as defined by transesophageal echocardiography (TEE) in 98 anesthetized patients before coronary artery bypass grafting. Measurements were made five times in each patient, before and after induction of anesthesia. Myocardial ischemia was identified by TEE in 14 patients; in 10 of these, it was associated with concomitant ST segment depression of at least 1 mm. The onset of ischemia, as defined by TEE, was accompanied by a mean increase in PCWP of 3.5 +/ 4.8 mm Hg, as compared with a mean change of 0 +/- 2.2 mm Hg between observations not associated with the onset of ischemia (p less than 0.01). An increase in PCWP of at least 3 mm Hg, tested as an indicator of ischemia, had a sensitivity of 25% and a positive predictive value of 15%; after correction for background changes associated with anesthetic induction, the sensitivity of this indicator was 33%, and its positive predictive value was 16%. These figures were not improved by selecting cutoff points higher or lower than 3 mm Hg. In this study, the onset of myocardial ischemia was associated with a small yet significant increase in mean PCWP at group level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306836 TI - Paradoxical narrowing of atherosclerotic coronary arteries induced by increases in heart rate. AB - Vasodilation in normal and vasoconstriction in atherosclerotic coronary arteries have been observed in response to complex stimuli such as exercise and the cold pressor test. To study a single parameter that changes during these activities, and to better understand the pathophysiology of ischemia associated with increases in heart rate, we studied coronary vasomotion and blood flow response to increasing heart rate alone, produced by atrial pacing, with quantitative angiographic and Doppler flow-velocity measurements in 15 patients. In five patients with angiographically smooth coronary arteries (group 1), tachycardia produced progressive dilation of the epicardial artery with increases in cross sectional area (CSA) of +15.5 +/- 3.4%, +22.4 +/- 2.1%, +28.5 +/- 3.3%, and +30.6 +/- 2.2% at 90, 110, 130, and 150 beats/min, respectively. In contrast, in five patients with mild angiographic narrowings (group 2), coronary segments failed to dilate with progressive tachycardia (-6.3 +/- 2.0%, -8.3 +/- 2.0%, -12.5 +/- 2.0%, and -11.4% at 90, 110, 130, and 150 beats/min, respectively), and progressive loss of luminal area was observed in five patients with severe angiographic narrowings (group 3) (-34.4 +/- 3.4%, -49.6 +/- 2.2%, -59.2%, and 72.8% at 90, 110, 130, and 150 beats/min, respectively). Coronary blood flow increased significantly with tachycardia in group 1 (+44.5 +/- 10.2%, +86.0 +/- 24.6%, +105.8 +/- 29.3%, and +137.5 +/- 46.0%), increased slightly in group 2 (+7.8 +/- 3.2%, +9.4 +/- 4.4%, +8.4 +/- 3.9%, and +10.0%), and decreased significantly in group 3 (-31.8 +/- 6%, -42.6 +/- 10.7%, -61.0%, and -70.0%). We conclude that an isolated increase in heart rate in patients with normal coronary arteries results in a modest increase in flow and vasodilation. In early atherosclerosis, the flow increase is blunted and dilation is replaced with paradoxical loss in luminal size. In patients with stenoses, further loss in luminal size occurs accompanied by a decrease in coronary blood flow. Thus, increasing heart rate alone in the setting of coronary stenoses could produce myocardial ischemia by a reduction in coronary supply, as well as by an increase in oxygen demand. PMID- 2306838 TI - Value of acceleration flows and regurgitant jet direction by color Doppler flow mapping in the evaluation of mitral valve prolapse. AB - To clarify the role of color Doppler echocardiography in the evaluation of mitral valve prolapse, we studied 49 consecutive patients in whom the sites of mitral valve prolapse were confirmed at the time of operation. The study group consisted of 22 patients with anterior leaflet prolapse, 24 patients with posterior leaflet prolapse, and three patients with multiple scallop prolapse (one patient with both anterior leaflet and middle scallop prolapse, and two patients with both medial and lateral scallop prolapse). Two-dimensional echocardiographic diagnosis of anterior leaflet prolapse was correct in all patients. The diagnosis of posterior leaflet prolapse by two-dimensional echocardiography, however, was mistaken as anterior leaflet prolapse in 16 (13 patients with medial scallop prolapse and three patients with lateral scallop prolapse) of the 24 patients according to current diagnostic criteria for mitral valve prolapse. Eight patients with middle scallop prolapse were diagnosed correctly by two-dimensional echocardiography. Acceleration flows in the left ventricle were observed by color Doppler echocardiography in all 49 patients. The sites of acceleration flows detected by color Doppler echocardiography coincided with those of prolapse confirmed in all at the time of operation. There was a significant correlation between the maximum area of acceleration flow signals and severity of mitral regurgitation estimated by angiography. In the 13 patients with medial scallop prolapse and the three patients with lateral scallop prolapse, a regurgitant jet originated from a bulged portion of the posterior leaflet and was directed toward the opposite left atrial cavity to the bulged portion by short-axis images of color Doppler echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306839 TI - Resting electrocardiographic abnormalities suggestive of asymptomatic ischemic heart disease associated with non-insulin-dependent diabetes mellitus in a defined population. AB - The prevalence of ischemic heart disease (IHD) in older adults by glucose tolerance status was evaluated in 2,223 white men and women, aged 50-89 years, in the Rancho Bernardo cohort who were studied between 1984 and 1987. Impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) were classified according to World Health Organization criteria. End points of ischemic heart disease were defined by Rose Questionnaire and resting electrocardiogram (ECG) according to the Minnesota Code. IHD by electrocardiographic changes was classified as asymptomatic (without history of chest pain or overt IHD) or symptomatic (with history). IHD by all criteria combined was significantly more common in men and women with NIDDM, and in women with IGT, than in those with normal glucose tolerance. The prevalence of myocardial infarction, defined by major Q wave, Rose Questionnaire chest pain criteria, or personal history, was higher in persons with NIDDM than in persons without; the difference was highly significant in women (odds ratio, 2.08 [1.22, 3.56]; p = 0.009). Angina pectoris was not significantly related to NIDDM or IGT in either sex. Electrocardiographic evidence of asymptomatic IHD was significantly more prevalent in both men and women with NIDDM as compared with those with normal glucose tolerance (odds ratios, 1.75 [1.10, 2.81] for men and 1.80 [1.07, 3.01] for women; p less than 0.05). This significant association persisted after excluding persons on digitlis or diuretic therapy and, in women, was also independent of the effect of major known IHD risk factors. These population-based data are consistent with clinical reports suggesting an association of diabetes with silent myocardial infarction or ischemia. The presence of ischemic resting electrocardiographic abnormalities in the asymptomatic diabetic patient is likely to have prognostic and therapeutic implications. PMID- 2306840 TI - Peripartum myocarditis and cardiomyopathy. AB - The clinical and pathologic features of 18 consecutive patients with peripartum cardiomyopathy at The Johns Hopkins Hospital were examined in an attempt to define the incidence of myocarditis and to determine its response to immunosuppressive agents. In addition to routine studies, patients were evaluated with echocardiography, nuclear ventriculography, right heart catheterization, and myocardial biopsy. Fourteen of the 18 patients (78%) showed evidence of myocarditis. Of these, 10 were treated with immunosuppressive therapy. Nine of the 10 treated patients with myocarditis had subjective and objective improvement. Follow-up endomyocardial biopsies in these patients showed resolution or substantial improvement in myocarditis. Four patients with myocarditis not treated with immunosuppressives also improved. All patients improving spontaneously presented with congestive heart failure within 1 month of delivery and improved dramatically within days of presentation. Four of the 18 patients showed no evidence of myocarditis. Of these, two improved, and two deteriorated (both requiring cardiac transplantation). None of these four patients were treated with immunosuppressive therapy. We conclude that in patients with peripartum cardiomyopathy, 1) the etiology remains unclear although myocarditis was present in 78% of those with this condition, 2) resolution of myocarditis is associated with significant improvement in left ventricular function, 3) myocarditis may resolve spontaneously without detectable loss of cardiac function, and 4) immunosuppressive therapy in patients with myocarditis and persistent left ventricular dysfunction may improve left ventricular function and prognosis. PMID- 2306841 TI - Fibrosis in the transplanted heart and its relation to donor ischemic time. Assessment with polarized light microscopy and digital image analysis. AB - Long-distance procurement of cardiac allografts is commonly used to increase the supply of donor organs but has recently been associated with the development of impaired diastolic function. Therefore, the effect of the total ischemic duration on myocardial fibrosis was quantitatively evaluated in 36 cardiac transplant recipients in whom the ischemic time ranged from 70 to 363 (mean, 189 +/- 83) minutes. Interstitial collagen was quantified with polarization microscopy and digital image analysis in 115 endomyocardial biopsy specimens taken 5-10 days after surgery. The technique, developed for this study, showed excellent correlation with hydroxyproline analysis (r = 0.98, p less than 0.001). Collagen volume fraction in biopsy specimens from the transplanted hearts was significantly greater than that in biopsy samples from seven normal, age-matched autopsy hearts (4.7 +/- 1.9% vs. 2.9 +/- 0.6%, p less than 0.02). The degree of fibrosis correlated with the total ischemic time (r = 0.60, p less than 0.001). Donor age ranged from 10 to 51 years and did not correlate with the degree of fibrosis. No relation was found between the corresponding collagen content and right atrial pressure, pulmonary artery wedge pressure, or cardiac output measured at the time of biopsy. Myocyte damage was observed in eight of the 36 patients and was characterized by a striking loss of muscle birefringence. We conclude that cardiac allograft fibrosis may be identified shortly after transplantation and is dependent on the total ischemic duration. PMID- 2306842 TI - Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes. AB - The incidence of fatal coronary heart disease (CHD) was determined in a population of Pima Indians from the Gila River Indian Community in Arizona. Between 1975 and 1984, 394 deaths occurred among 4,828 subjects aged 5 years or older, and 199 of these occurred in the 1,093 persons with non-insulin-dependent diabetes. Only 28 deaths were attributed to CHD; all occurred among the 689 diabetic persons 45 years of age or older. No CHD deaths occurred among the 419 nondiabetic subjects 45 years of age or older. The rate of fatal CHD among the diabetic subjects was higher in men than in women and increased with advancing age and duration of diabetes. A higher incidence of fatal CHD was associated with proteinuria, renal insufficiency, medial arterial calcification, diabetic retinopathy, insulin therapy, and an abnormal electrocardiogram. In Pima Indians aged 50-79 years, the incidence of fatal CHD was less than half that found in the Framingham population after controlling for age, sex, and diabetes (incidence rate ratio, 0.4; 95% confidence interval, 0.2-0.7). Factors protecting Pima Indians from fatal CHD may include racial heritage, low serum concentrations of total and low density lipoprotein cholesterol, and rarity of heavy smoking. Among the diabetic subjects, mortality from diabetic renal disease, which shows many of the same risk factors, may selectively compete and remove those at risk for fatal CHD. This would not, however, explain the lack of fatal CHD among the nondiabetic subjects. Fatal CHD shares many of the risk factors associated with the specific microvascular complications of diabetes, and diabetes and its associated attributes are the major predictors of fatal CHD in this population. PMID- 2306844 TI - New frontiers in interventional cardiology. A symposium. Naples, Florida, October 7-9, 1988. Proceedings. PMID- 2306843 TI - Detrimental sequelae on the hemodynamics of the upper left limb after subclavian flap angioplasty in infancy. AB - The long-term effect of two surgical techniques for repair of coarctation of the aorta in infancy, namely, resection and end-to-end anastomosis (RETE) and subclavian flap angioplasty (SFA) on the blood supply of the upper left limb, was quantified by Doppler spectrum analysis of blood flow velocities in the left brachial artery at rest and during postocclusive reactive hyperemia. Twenty-three patients participated in this study: nine patients after SFA (median age, 8 years), 14 patients after RETE (median age, 8 years), and 10 control subjects (median age, 9.5 years). At rest, a highly significant decrease of blood flow velocities in the left brachial artery was measured in all patients of the SFA group compared with those of the RETE and control groups, as documented by various Doppler spectrum parameters: maximal frequency of advancing curve (p = 0.0001), pulsatility index (p = 0.0005), and resistance index (p = 0.039). During reactive hyperemia, a moderate capacity of physiologic augmentation of blood flow velocities was observed in five patients of the SFA group. This capacity was marginal in two patients with complaints of claudication in the left upper limb during strenuous exercise, which can be related to the number of branches of the left subclavian artery ligated during operation. This study indicates that SFA in infancy may lead to compromised hemodynamics of the upper left limb with potential for symptoms of ischemia during exercise. PMID- 2306845 TI - Laser balloon angioplasty. A new approach to abrupt coronary occlusion and chronic restenosis. AB - Abrupt coronary occlusion and long-term restenosis continue to be the major problems associated with percutaneous transluminal coronary angioplasty (PTCA). Laser balloon angioplasty (LBA) is a technique designed to potentially alleviate these problems by sealing arterial dissections, smoothing the luminal surfaces, dehydrating thrombi, and reducing the elastic properties that tend to recoil the stretched artery to its original state. During LBA, laser energy is delivered circumferentially by a 100-microns optical fiber that terminates in a central diffusing tip within an angioplasty balloon. LBA is performed for 20 seconds during the final inflation of the angioplasty balloon. Achieved with decremental ramped laser dosimetry, Nd:YAG laser energy has been shown to be effective in welding experimental arterial dissections over a therapeutic temperature range of 95 degrees-120 degrees C. LBA treatment of rabbit iliac arteries has been superior to balloon angioplasty in inhibiting elastic recoil and causing acute and long-term luminal increment. LBA has also been effective for sealing acute dissections in atherosclerotic rabbit iliac arteries. Additionally, in a canine model, safety in the coronary circulation has been shown, that is, even at 1 month after LBA, angiography demonstrated a cast of the LBA balloon without luminal compromise. Since March 1988, more than 250 patients with symptomatic coronary artery disease have been treated with LBA with nearly uniform clinical success, including frequent reversal of abrupt closure. LBA seems to be a safe modality that may decrease the need for emergency operative procedures and late coronary revascularization after PTCA. PMID- 2306846 TI - Myocardial dysfunction during percutaneous transluminal coronary angioplasty. AB - Balloon inflation during percutaneous transluminal coronary angioplasty (PTCA) transiently occludes the coronary artery, causing temporary ischemia. In patients without collaterals, regional hypokinesis of the ventricular myocardium at risk occurs within the first 20 seconds and persists throughout balloon inflation. Early PTCA procedures were performed with brief balloon inflations, but the desire to improve procedural results has led many operators to extend balloon inflation times to 45 seconds or longer. Although the ischemic indicators of pain and electrocardiographic changes are commonly noted with these longer inflations, actual hemodynamic consequences are often obscured by physiological compensation. The PTCA-induced ischemic period is often too short to measure changes in cardiac output by conventional methods, but it is increasingly evident that profound regional myocardial dysfunction, in fact, occurs. Continuous two-dimensional echocardiography with quantitative assessment of regional wall motion and ejection fraction is particularly effective in detecting the location, extent, and temporal change of ischemic regional contractile dysfunction. Echocardiographic recordings during baseline, ischemia, and post-balloon deflation periods permit examination of PTCA-caused alterations in ejection fraction and ventricular volumes and allow the use of testing techniques aimed at mitigation of ischemia. PMID- 2306847 TI - Perfluorochemical perfusion during coronary angioplasty in unstable and high-risk patients. AB - Perfluorochemical perfusion during coronary angioplasty was performed in 38 patients with unstable ischemic syndromes or with high-risk lesions in a single blind crossover study. Patients received alternate 90-second balloon inflations with and without distal perfusion of oxygenated perfluorochemical (Fluosol, Alpha Therapeutic Corp., Los Angeles, California) at 60 ml/min. Efficacy was assessed by anginal intensity, hemodynamic and electrocardiographic parameters, and left ventricular function determined by two-dimensional echocardiography during balloon inflations. There was a trend toward lower anginal intensity with Fluosol perfusion at 30, 60, and 90 seconds of occlusion. Pulmonary wedge pressure increased significantly with and without Fluosol perfusion, and the magnitude of change was not different. Cardiac output decreased significantly less with Fluosol perfusion than with routine inflation for the total group (-0.8 vs. -1.2 l/min, p less than 0.01) and in the subgroup with left anterior descending coronary artery (LAD) angioplasty (-0.7 vs. -1.5 l/min, p less than 0.001). Left ventricular ejection fraction (EF) by echocardiography declined significantly less with Fluosol perfusion (-4.0 vs. -7.9 EF units, p less than 0.004) than with routine inflation for the total population and declined significantly less with Fluosol in the subgroup with LAD angioplasty (-5.5 vs. -9.7 EF units, p less than 0.008). Regional wall-motion abnormality score increased significantly with routine inflation (from 0.7 +/- 1.4 to 3.5 +/- 3.2, p less than 0.001) and did not change with Fluosol perfusion (from 0.8 +/- 1.3 to 1.3 +/- 1.1, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306848 TI - Coronary venous synchronized retroperfusion during percutaneous transluminal angioplasty of left anterior descending coronary artery. AB - Synchronized coronary venous retroperfusion was applied and studied in 16 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) balloon dilatation of proximal left anterior descending (LAD) coronary artery stenosis. The rationale for using retroperfusion support during the PTCA-induced coronary artery occlusions was to ameliorate or prevent myocardial ischemia and possibly facilitate extension of the PTCA balloon-inflation period. After therapeutic PTCA treatment, which successfully dilated the culprit coronary artery in all 16 patients, and a 5-minute recovery period, a single retroperfusion-treated LAD occlusion (101 +/- 36 seconds) was compared with equivalent untreated control LAD occlusions (86 +/- 24 seconds) before and after the retroperfusion-supported balloon occlusion. Observations and measurements encompassed 1) ease and time of coronary sinus catheterization, 2) incidence of anginal pain during LAD occlusion, 3) electrocardiographic signs of myocardial ischemia, and 4) two dimensional echocardiographic indexes of global left ventricular function. The coronary sinus was successfully catheterized within 139 +/- 140 seconds, and in 12 of the 16 patients, the tip of the special autoinflatable retroperfusion balloon catheter could be placed in the desired location of the great cardiac vein. The retroperfusion protocol interfered minimally with the PTCA procedure, and application of the support system had no deleterious effects. As compared with the pain reported 23 (72%) times during the 32 control LAD occlusions, only five (31%) of the patients indicated pain or discomfort during the retroperfused occlusions. Treated occlusions exhibited delayed or significantly lower electrocardiographic ST segment elevations (sum, 10.4 +/- 7.8 mm) as compared with the controls (sum, 16.2 +/- 7.9 mm and 18.8 +/- 10.6 mm; both p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2306849 TI - Prediction of acute closure in percutaneous transluminal coronary angioplasty. AB - Despite significant advances in the technology of percutaneous transluminal coronary angioplasty (PTCA) and the ability to perform the procedure in more complex cases, there are still problems of acute closure and resultant acute myocardial infarction. Approximately two thirds of patients who undergo acute closure will require bypass surgery. Independent factors that can be predictive of patients who will undergo acute closure include stenosis length exceeding a two-lumen diameter, female gender, stenosis at a bend of 45 degrees or more, stenosis at a branching point, stenosis-associated thrombus or filling defect, other stenoses in the vessel undergoing dilatation, and multivessel disease. Factors that can be identified only at the time of the procedure are post-PTCA percentage of stenosis, an intimal tear or dissection, and a post-PTCA gradient of 20 mm Hg or more. The outcome of abrupt closure depends on several factors. The features that have been found to be predictive of fatal outcome are female gender, collateral channels originating from the dilated vessel, a large amount of jeopardized myocardium, left ventricular hypertrophy, hypertension before PTCA, diabetes, and multivessel disease. When abrupt closure occurs, attempts should be made to reopen the artery even if a decision has been made to proceed to bypass surgery. Techniques that can help when the artery cannot be kept open include prolonged inflation (3-5 minutes), use of a bailout or perfusion catheter, and infusion of an oxygenated perfluorochemical (Fluosol, Alpha Therapeutic Corp., Los Angeles, California). Intracoronary stenting and laser balloon angioplasty are new techniques that might prove useful in the management of the dissection that commonly leads to abrupt closure. PMID- 2306850 TI - Emergency "rescue" percutaneous transluminal coronary angioplasty after failed thrombolysis with streptokinase. Early and late results. AB - Although thrombolytic therapy has been a major advance in the treatment of acute myocardial infarction, in at least 25% of patients the artery remains occluded after administration. In these patients, the strategy of "rescue" or "salvage" angioplasty is frequently used although follow-up data are limited. Sixty-three patients underwent percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction. The decision to proceed with PTCA was based on physician preference and not a specific research protocol. In 34 of these selected patients, PTCA was performed as a rescue procedure because the infarct-related artery remained occluded (group 1); in 29 of these patients, it was performed to treat a severe but subtotal residual stenosis (group 2). PTCA successfully restored patency in 71% of group 1 and in 90% of group 2. Group 1 patients had a significantly worse baseline ejection fraction than did those in group 2 (47 +/- 13% vs. 58 +/- 13%, p = 0.0015). Group 1 patients also had a significantly worse predismissal ejection fraction (36 +/- 13% vs. 50 +/- 14%, p = 0.0004). During initial hospitalization, 14 (22%) patients underwent coronary bypass surgery. In-hospital mortality was low in each group (3% in group 1 and 0% in group 2). During a mean follow-up of 4 years, 89% of group 1 patients remained alive as compared with 97% of group 2 patients. This excellent 4-year survival rate, despite the depressed predismissal ejection fraction in patients undergoing rescue PTCA, raises the issue of whether acute reperfusion has a beneficial effect aside from any impact on myocardial salvage and preservation of left ventricular function. PMID- 2306851 TI - Directional atherectomy. New approaches for treatment of obstructive coronary and peripheral vascular disease. AB - Atherectomy is defined as the controlled removal of atherosclerotic tissue from vessel walls. The directional atherectomy catheter consists of a cup-shaped cutter within a housing unit and a small balloon. It was developed to perform transluminal atherectomy for the treatment of atherosclerotic vascular disease. This new procedure was performed on 195 lesions in peripheral arteries of lower limbs in 134 procedures, and 52 lesions in coronary arteries in 50 procedures. A successful angiographic outcome was obtained in 89% of procedures and 90% of lesions in peripheral experience, and 60% of procedures and 62% of lesions in coronary experience. A higher success rate (81%) was achieved in our more recent experience with coronary atherectomy, as compared with a 42% success rate in our earlier experience. The incidence of major complications was infrequent in both peripheral and coronary experiences. In the peripheral experience, one patient had delayed occlusion that required bypass surgery, and two patients had distal embolization. In the coronary experience, one patient had acute occlusion that required emergency bypass surgery. There were no vessel perforations. Conclusively, transluminal atherectomy is a feasible, predictable, and safe procedure for the treatment of peripheral and coronary artery disease. Further studies, however, are necessary to evaluate the long-term efficacy of this new procedure. PMID- 2306852 TI - Intracoronary stenting during percutaneous transluminal coronary angioplasty. AB - A flexible, balloon-mounted, coil stent was developed to address the problems of acute closure and long-term restenosis, which currently limit the safety and efficacy of percutaneous transluminal coronary angioplasty. The device is made of 0.006-in. stainless steel suture material and is mounted on balloons, 2.5-4.5 mm in diameter, for use in the coronary circulation. Results of studies in canine coronary arteries have demonstrated long-term patency and stability, and studies in the atherosclerotic arteries of rabbits have suggested late results with stenting that might be superior to those obtained with balloon angioplasty alone. Initial clinical studies have focused on the use of the device as a "bridge" to surgery if closure occurs. The stent appears to have been successful in this application. A phase 2 study is now examining the stent as definitive therapy for acute closure in certain anatomic subsets of patients. Information on long-term patency is pending. If this is favorable, the device will be studied to see if it reduces the incidence of restenosis in the subset of patients in whom balloon dilatation alone fails to produce an optimal hemodynamic result. PMID- 2306853 TI - Microbial keratitis and corneal ulceration associated with therapeutic soft contact lenses. AB - We reviewed the records of 22 patients whose corneal ulcers were associated with therapeutic soft contact lens wear. The patients required hospitalization on the Cornea Service at Wills Eye Hospital between January 1, 1978 and September 1, 1988. A majority of the ulcers were associated with pseudophakic or aphakic bullous keratopathy (9 of 22 cases; 41%); neurotrophic/exposure keratitis was the second most common diagnosis (7 of 22; 32%). Most patients used topical antibiotics (15 of 22; 68%) and/or corticosteroids (13 of 22; 59%). Cultures were positive in 15 of 22 cases (68%). Gram-positive organisms were isolated in 60% the culture-positive cases (9 of 15). Streptococcus was the most common organism isolated (6 of 15 culture positive-cases; 40%). Gram-negative organisms were found in four of 15 culture-positive ulcers (27%). There was only one Pseudomonas infection in the series. Uncommon organisms--including Candida, atypical mycobacteria, Achromobacter, Acinetobacter and Micrococcus--were isolated in five cases. Therapeutic soft contact lens wearers are at risk for developing corneal ulcers; most often these are caused by gram-positive bacteria, especially streptococci, and uncommon organisms. PMID- 2306854 TI - Fluoroperm extended wear RGP contact lenses: II. Front toric fitting. AB - Seventeen eyes (10 patients) were fit with front toric rigid gas permeable (RGP) Fluoroperm lenses as part of an extended wear study. These 17 eyes required 40 fittings (an average of 2.35 fittings per eye); only six eyes were fit successfully the first time. What occasioned the large number of fittings was unacceptable visual acuity due to incorrect lens axis. Most fittings had been done with a polymethylmethacrylate (PMMA) fitting set; and it became obvious that the final Fluoroperm lenses rotated differently from the PMMA diagnostic lenses. Ultimately, the use of a Fluoroperm prism-ballasted fitting set resulted in 16 of 17 eyes (94%) seeing well with a front toric lens. We advise that, for front toric fittings, the diagnostic lens be of the same material as the final lens. PMID- 2306855 TI - Tear volume in relation to contact lens wear and age. AB - We examined the tear volume of the inferior conjunctival sac in relation to patient age and complications of contact lens wear using a special phenol red thread test. Records of patients who had undergone this test between 1984 and 1987 were reviewed. Based on the wet length of the thread, three groups were defined: 9 mm or less, 10-14 mm, and 15 mm or more. Those patients who showed consistent results over three or more separate testings were selected for this study. A total of 11,336 eyes met this criterion. A confidence interval of 95% was established as a basis for comparison of the groups. We found that the percentage of eyes with 9 mm or less of wet length increased with the age of the subject group. Likewise, the percentage of each age group with 15 mm or more of wet length steadily decreased among progressively older groups. Eyes wearing PMMA lenses with 9 mm or less of wet length showed the highest incidence of superficial punctate keratitis (SPK) and erosion. The group of eyes wearing high DK lenses with 15 mm or more of wet length showed the lowest incidence of SPK and erosion. PMID- 2306856 TI - Personality and keratoconus. AB - We studied personality traits of patients with keratoconus in a controlled prospective study using the Minnesota Multiphasic Personality Inventory (MMPI). Whereas four of 16 (25%) control patients with herpes simplex keratitis had scores indicative of psychological abnormality, 15 of 28 (54%) keratoconus patients had scores indicative of abnormality (P less than .05). Keratoconus patients who had undergone penetrating keratoplasty had a lower rate of abnormal scores (3 of 9; 33%) than unoperated keratoconus patients (12 of 19; 63%) (P less than .05). Patients who considered themselves moderate or severely limited by their eye condition were more likely to have abnormal scores (7 of 8; 87%) than patients who thought they were mildly affected (8 of 20; 40%) (P less than .05). PMID- 2306857 TI - Ulcerative keratitis and the future of contact lens wear. PMID- 2306858 TI - Hydrogen peroxide in anterior segment physiology and contact lens care: a 20th anniversary roundtable. September 17, 1989. Proceedings. PMID- 2306859 TI - Effect of hydrogen peroxide on epithelial light-scattering and stromal deturgescence. AB - The anterior epithelium of the cornea is particularly sensitive to toxic solutions. A zone of increased light-scattering in the anterior epithelium, the anterior bright band (ABB), increases in thickness when exposed to toxic substances, but is not affected by benign solutions. With some solutions the thickness of the stroma also increases. The endothelial surfaces of rabbit corneas were perfused in vitro at 35 degrees C with various solutions, and the ABB and stromal thickness determined by specular microscopy. With glutathione bicarbonate Ringer as control, the epithelium was bathed with concentrations of hydrogen peroxide (H2O2) at 72, 153, and 235 ppm with either a 10-minute pulse dose or a sustained dose of 150 minutes. In the 10-minute pulse-dose experiment, the H2O2 concentrations caused no significant changes in the ABB or stroma when compared with the control. In the 150-minute sustained-dose experiment, significant changes in both the ABB and stroma thickness were noted at the 153 and 235 ppm concentrations, but the 72 ppm dose caused no significant change. Exposure to benzalkonium chloride for 150 minutes produces a greater increase in both ABB and stromal thickness than does exposure to 235 ppm hydrogen peroxide. PMID- 2306860 TI - Cellular injury from sustained vs. acute hydrogen peroxide exposure in cultured human corneal endothelium and human lens epithelium. AB - The duration of hydrogen peroxide (H2O2) exposure was examined in confluent monolayers of human corneal endothelium (HCE) and human lens epithelium (HLE) by comparing 3-minute, 15-minute, 30-minute, and 90-minute treatment protocols. The cells showed remarkable ability to withstand high doses of H2O2 (1 mM, approximately 30 ppm) for up to 30 minutes without noticeable morphologic alterations or decreases in rubidium-86 chloride (86RbCl) uptake (a marker used to evaluate damage to the cells' active transport properties). In contrast, when H2O2 levels were maintained for 90 minutes, a substantially lower dose (0.1 mM, approximately 3 ppm) produced cell death, morphologic alterations, and depression of 86RbCl uptake. The marked difference in the dose-response for injury also appeared to be associated with a decrease in cells' abilities to remove H2O2 from the tissue culture medium. Knowledge of the time-dependency for H2O2 damage may be useful in the design of future in vitro studies concerning H2O2 effects, and may help explain the apparent lack of major cellular damage in vivo if topical H2O2 solutions are removed rapidly from the eye. PMID- 2306862 TI - Common physical presentations of psychiatric disorders. PMID- 2306861 TI - Biocompatibility of hydrogen peroxide in soft contact lens disinfection: antimicrobial activity vs. biocompatibility--the balance. AB - Critical factors of soft contact lens care include adequate disinfection and neutralization of the chemical constituents of the disinfecting system before reinsertion. Three cases of microbial keratitis are described that exemplify the critical nature of disinfection with adequate antimicrobial activity. Disinfection rates are described for a 3% solution of hydrogen peroxide (H2O2) against multiple microorganisms. The results indicate that H2O2 is equivalent to heat disinfection when used for appropriate lengths of time. Problems associated with chemical disinfection include lens fit alterations, which may lead to epithelial trauma. However, unless antimicrobial chemicals can be rinsed, neutralized, or degraded, they can also injure the corneal and conjunctival epithelium. Repeated exposure of the corneal epithelium to oxidizing agents renders it vulnerable to complications. PMID- 2306863 TI - Septic sternoclavicular arthritis: diagnostic clues and management. PMID- 2306864 TI - Treatment strategy for coronary artery disease: a balancing act. PMID- 2306865 TI - Development of policies on brain death, care of the hopelessly ill, and do not resuscitate. PMID- 2306866 TI - Policy statements: do not resuscitate, care of the hopelessly ill, and brain death. Ethics Committee of the Cleveland Clinic Foundation. PMID- 2306867 TI - Octreotide: a hormone for all diseases? AB - Octreotide is a new agent with many documented useful applications and a huge number of possible applications. Each documented therapeutic effect will require careful analysis. Particular care must be taken to design controls, use double blind tests for objective study of subjective benefits, and frame questions to elicit precise answers. The most important guide is to keep an open mind when attempting to discern a mechanism of action. PMID- 2306868 TI - Early exercise testing following percutaneous transluminal coronary angioplasty. AB - The value of early symptom-limited stress electrocardiography following percutaneous transluminal coronary angioplasty in assessing late outcome was evaluated in 218 patients. All subjects were tested using the Bruce or Sheffield Protocols, 2.5 +/- 1.3 days after percutaneous transluminal coronary angioplasty. Repeat coronary angiography was performed after percutaneous transluminal coronary angioplasty because of symptoms (58%) or as routine follow-up (42%). Stress electrocardiography results were compared to coronary angiography. The sensitivity and specificity were 35.3% and 52.6%, respectively. The positive and negative predictive values were 39.6% and 48.0%. Two acute myocardial infarctions and one coronary angiographic-proven restenosis occurred within hours of the stress electrocardiogram in three patients (1.4%). It is concluded that symptom limited stress testing immediately following percutaneous transluminal coronary angioplasty has no prognostic value and may carry increased risk for immediate negative coronary events. PMID- 2306869 TI - Patient-controlled analgesia for postcholecystectomy pain: a pilot study. AB - Patient-controlled analgesia (PCA) is designed to avoid both excessive and inadequate analgesia in postoperative pain by allowing the patient self administration of intravenous narcotics within a range of parameters established by the physician. Of 24 patients undergoing elective cholecystectomy referred to our study over a 12-month period, 11 were assigned to PCA and eight successfully completed the study. Most of them had good analgesia, were satisfied with PCA, and had no evidence of confusion, psychic distress, or visual-motor impairment. Serum morphine concentrations of 10-30 ng/mL were sufficient to obtain good analgesia in six of eight patients. Complications included severe respiratory depression and abdominal cramps. PMID- 2306870 TI - Treatment of psoriasis with chronic subcutaneous administration of somatostatin analog 201-995 (sandostatin). I. An open-label pilot study. AB - Increased levels of human growth hormone (HGH) may correlate with the severity of psoriasis and native somatostatin (SRIF) may improve it by inhibiting HGH release. The synthetic SRIF analog, SMS 201-995, is a potent and long-lasting HGH inhibitor. Nine patients with chronic plaque psoriasis completed 12 weeks of open treatment with SMS 201-995. Overall improvement was minimal to marked in six patients and unchanged in three; none worsened. Means of 24-hour pooled HGH (1.7 +/- 0.7 micrograms/L) and fasting plasma somatomedin-C (SM-C) (0.45 +/- 0.22 U/mL) were normal at baseline and were not significantly altered by treatment. A high frequency of gastrointestinal side effects occurred, but no patient discontinued treatment because of them. SMS 201-995 may be a useful therapy for psoriasis, but its mechanism of action is unknown. Double-blind placebo controlled trials are currently in progress to confirm the efficacy of SMS 201 995 in psoriasis. PMID- 2306871 TI - Distal hypospadias in the adult. AB - The majority of patients with distal hypospadias undergo surgical reconstruction in childhood for social, emotional, and technical reasons. Rarely, patients with hypospadias do not receive repair during childhood and seek surgical treatment as adults. The authors recently performed reconstruction on two adult patients with primary distal hypospadias. One patient had voiding problems, necessitating sitting, and the other patient desired repair for cosmetic reasons. In performing the surgical repair, the authors observed that the amount, as well as the elasticity, of the redundant foreskin was less in adults than in children. Urologists with a full repertoire of surgical skills can expect excellent results in patients with primary distal hypospadias. PMID- 2306872 TI - Extralobar pulmonary sequestration. AB - A neonate presenting with a density of the right mid-thorax was found, at thoracotomy, to have an extralobar pulmonary sequestration. The sequestration was resected, and the infant made an uneventful recovery. The morphogenesis, diagnosis, and management of this uncommon lesion are discussed. PMID- 2306873 TI - Rapid identification of the external jugular vein. AB - The authors describe a rapid technique to identify the course of the external jugular vein based on the location of the cephalic vein or the deltopectoral groove. PMID- 2306874 TI - Re: Carcinoma of the prostate presenting as inguinal adenopathy. PMID- 2306875 TI - Re: Facial fuzz and funny findings. PMID- 2306876 TI - Effects of dopamine on blood pressure and heart rate after microinjection into the hypothalamus of spontaneously hypertensive and normotensive Wistar-Kyoto rats. AB - In anaesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats, 0.0125-0.4 mg/kg dopamine (DA) given intracerebroventricularly (icv) produced dose-related decreases in mean arterial blood pressure (MAP) and heart rate (HR), whereas intravenous DA produced dose-related increases in MAP and HR. SHR was significantly more responsive to icv DA compared with the normotensive controls. DA (0.02 mg/kg) significantly reduced MAP in a biphasic manner, when microinjected into the arcuate nucleus or third ventricle of SHR, with no significant changes in HR. No such effect occurred in WKY rats. Metoclopramide given concurrently with DA into the third ventricle attenuated the hypotensive response to DA. Saline injection had no significant effect on MAP and HR. The hypotensive responses to DA were not confounded by the spread of injected DA into the adjacent hypothalamic areas. These results support the hypothesis that there exists an abnormal sensitivity in SHR to centrally administered DA and that the arcuate appears to be the brain site involved in this abnormality. PMID- 2306877 TI - Highly sensitive microplate-ELISA for angiotensin I using 3,3', 5,5' tetramethylbenzidine. AB - A microplate-ELISA was established for angiotensin (Ang) I using Ang I-peroxidase conjugate, antiAng I antibodies which could distinguish Ang I from Ang II and Ang III, and 3,3', 5,5'-tetramethylbenzidine. Ang I could be quantified in amounts as low as 1 pg by the spectrophotometric method. The present assay system was the most sensitive and rapid in all Ang I assay systems described so far. The assay system was applicable to determination of Ang I concentration in human plasma and abdominal fluid. PMID- 2306878 TI - Interleukin 1 enhances the development of spontaneous arthritis in MRL/lpr mice. AB - We previously reported that treatments with human recombinant interleukin-1 beta (rIL-1 beta) in DBA/1 mice which were suboptimally immunized with native chick type II collagen (NcII) markedly accelerated the onset of collagen-induced arthritis (CIA). In the present study, we further characterized this IL-1 mediated enhancement of murine arthritis by examining the in vivo effects of rIL 1 beta in another arthritis model, namely, the spontaneous arthritis of the MRL/lpr mouse strain. The results of these studies demonstrated that IL-1 treatments also enhanced the onset and progression of the spontaneous arthritic disease in MRL/lpr mice. A substantial proportion of the IL-1-treated MRL/lpr mice that were between 3 and 3.5 months of age exhibited swelling in either the hind or front paws. Moreover, histopathologic studies demonstrated the presence of striking alterations within the various joints of these IL-1-treated MRL/lpr mice. Such abnormalities were not detected in the non-IL-1-treated, age-matched MRL/lpr mice. Therefore, as in the experimentally induced disease of CIA, IL-1 may also be capable of contributing to the pathogenesis of the spontaneous arthritis of MRL/lpr mice. PMID- 2306879 TI - Combined complete C5 and partial C4 deficiency in humans: clinical consequences and complement-mediated functions in vitro. AB - A family is described with two siblings who suffered at different times from a single episode of meningococcal meningitis by Neisseria meningitidis groups B and C, respectively. In the two subjects, hemolytically active fifth component of complement (C5) was not detectable and antigenic C5 was less than 0.05% and less than 0.7% of normal, respectively. Repletion of sera by purified human C5 (70 micrograms/ml) restored total complement hemolytic activities. The asymptomatic first degree family members had C5 levels compatible with a heterozygous state of C5 deficiency. C4 allotyping revealed an inherited partial deficiency (Q0) of C4A and C4B in the family with a combined C4AQ0 and C4BQ0 heterozygous condition in one and C4BQ0 heterozygosity in the other C5 deficient (C5D) subject. To our knowledge, this is the first human kindred with recognized combined C5 and C4 deficiency. No other defect of the humoral and cellular immune system was found in this family, including specific immune response to tetravalent meningococcal vaccine. The effect of partial C4 deficiency on classical pathway function was assessed by inhibition of immune precipitation (IIP) of forming bovine serum albumin (BSA)/anti-BSA immune complexes. Sera from all family members showed normal IIP values, with exception of the subject with combined partial deficiency in C4A, C4B, and complete deficiency in C5. Despite undetectable functional C5 in the C5D sera, the titration of the alternative pathway indicated intact but deficient hemolytic activities when rabbit erythrocytes (EC) were used as indicator cells in the presence of Mg2+ and EGTA in an end-point or kinetic assay. Preincubation of the two sera at 0 degrees C for 60 min with rabbit ECs reduced alternative pathway hemolytic activity by 24 and 100%, respectively. When rabbit ECs were replaced by guinea pig ECs no alternative pathway function could be measured. The results indicate that the apparent functional activity of the alternative pathway in C5D sera strongly depends on a factor(s) present in such serum and/or on the detection system used. We conclude that the two C5D individuals of the family reported here may not have sufficient C5 activity to provide efficient protection against Neisserial infections in conditions where complement functions beyond C3 opsonic activity are required in vivo. PMID- 2306880 TI - Correction of human immunodeficiency virus-associated depression of delayed-type hypersensitivity (DTH) after zidovudine therapy: DTH, CD4+ T-cell numbers, and epidermal Langerhans cell density are independent variables. AB - Twenty-four patients with various degrees of human immunodeficiency virus (HIV) associated immunodeficiency were treated with zidovudine for up to 6 months. Nineteen of these patients had persistent depression of delayed-type hypersensitivity (DTH) responses prior to commencing therapy. In 11 of these 19 patients (58%) there was sustained improvement of DTH responses with the maximal effect occurring at approximately 3 months after therapy was started. DTH declined after 3 months but remained significantly higher than baseline at 6 months. Patients who did not have a sustained increase in DTH responses had more severe disease than those that did. Blood CD4+ T-cell counts increased in the majority of patients on zidovudine therapy, but varied independently of DTH responses. Epidermal Langerhans cell density was lower in HIV-infected patients than controls but also varied independently of DTH responses before and after zidovudine therapy. We suggest that sequential measurement of DTH responses is a valuable means of monitoring the restoration of cell-mediated immune responses by zidovudine in some HIV-infected patients. Our findings also demonstrate the need to define the processes involved in the restoration of DTH responses as this may lead to new approaches to the therapeutic manipulation of cell-mediated immune responses in HIV-infected patients. PMID- 2306881 TI - Dendritic cells and class II MHC expression on thyrocytes during the autoimmune thyroid disease of the BB rat. AB - The BB rat is a well-established model for spontaneous thyroid autoimmune disease. Since antigen presentation in thyroid autoimmunity is still a matter of debate, we studied the presence of antigen-presenting dendritic cells in the thyroid of the BB/O rat during the development of the disease in relation to the presence of other leucocytes and the aberrant expression of class II MHC determinants by thyrocytes. Thyroid glands, as well as thyroid-draining lymph nodes, were investigated in enzyme histochemistry and immune histochemistry. The appearance of anti-colloid antibodies in the circulation at 6 weeks of age was accompanied by an increase in the weight of the thyroid-draining cervical lymph nodes, which contained many anti-thyroglobulin-producing plasma cells. The only noteworthy event in the thyroid gland in this early stage of the disease was an increase in the number of dendritic cells. T cells, B cells, and plasma cells were virtually absent from the thyroid, and thyrocytes were invariably negative for class II MHC determinants. Only after 18 weeks of age, when large accumulations of dendritic cells, B lymphocytes, and T lymphocytes were seen in 40% of the BB thyroids, could some class II MHC positive thyroicytes be observed. At this stage the thyroid also contained some anti-thyoglobulin-producing plasma cells. Our observations suggest that dendritic cells play a role in antigen presentation in the early stages of the thyroid autoimmune response. PMID- 2306882 TI - Long-term prognosis in children with hypertrophic cardiomyopathy: an analysis of 37 patients aged less than or equal to 14 years at diagnosis. AB - The relation of clinical, electrocardiographic, and hemodynamic findings at diagnosis to presenting features and prognosis of hypertrophic cardiomyopathy in childhood was evaluated in 37 consecutive patients below 14 years of age at time of diagnosis (24 males and 13 females, mean age 7 +/- 4 years). A left ventricular out-flow tract gradient (mean 42 +/- 27 mmHg) was detected at cardiac catheterization in 13 (35%) patients. Clinical, electrocardiographic, and hemodynamic features in patients with and without a pressure gradient were similar. Patients who had moderate to severe functional limitation had a higher incidence of syncopal episodes (p less than 0.001), lower ejection fraction (p less than 0.01), raised pulmonary artery pressure (p less than 0.001), and left ventricular end-diastolic pressure (p less than 0.01). During a follow-up of 9.2 +/- 5.1 years (range 2-18), 9 (24%) patients died suddenly (2 with a recorded left ventricular outflow tract gradient). Univariate analysis showed that reduced ejection fraction (p = 0.0001), syncopal episodes (p = 0.003), increased left ventricular end-diastolic pressure (p = 0.03), and severe dyspnea (p = 0.04) were associated with a poor prognosis. However, multivariate analysis revealed ejection fraction (p = 0.0001) and syncopal episodes (p = 0.0097) as independent predictors of survival. In conclusion, sudden cardiac death was common and was well predicted by the combination of left ventricular dysfunction and syncope at time of diagnosis. PMID- 2306883 TI - Role of transmitral blood flow velocity by Doppler echocardiography in the evaluation of coronary artery disease. AB - To determine the relation between presence and severity of coronary artery disease and diastolic filling abnormalities by Doppler echocardiography, recordings of transmitral inflow velocity were made at rest in 90 patients with coronary artery disease and 28 normals. At the time of the Doppler examination, 81 patients with coronary artery disease (90%) and 10 normals (36%) were treated with antianginal medications. No difference was found in the ratio between early (E) and late (A) diastolic filling velocity (E/A ratio) when comparing patients with greater than 70% obstruction of at least one coronary artery to age-matched normals, regardless of the presence or absence of wall motion abnormalities. The E/A ratio was 1.3 +/- 0.46 in coronary patients with normal wall motion, 1.2 +/- 0.47 in coronary patients with abnormal wall motion, and 1.3 +/- 0.53 in both samples of age-matched normals. Multivariate analysis of the relation between E/A ratio and other variables showed that heart rate (F = 24.46, p less than 0.00001) and age (F = 19.51, p less than 0.00001) were significant independent determinants of the E/A ratio, while the presence or severity of coronary artery disease, the presence of hypertension, the magnitude of wall motion abnormalities, and end-diastolic dimension by echocardiography were not. These data suggest that transmitral inflow velocity recordings by Doppler have limited value for the recognition of coronary artery disease, since the E/A ratio is profoundly influenced by other factors, such as heart rate and age. PMID- 2306884 TI - Two unusual manifestations of aortic aneurysms. AB - Pain and pulsation are common presenting features of aortic aneurysms. Massive hematemasis and ureteral obstruction represent rare clinical presentations. This report describes a patient with massive hematemesis in whom a thoracic aneurysm ruptured into the esophagus, and a second patient in whom a large abdominal aortic aneurysm caused bilateral ureteral obstruction. PMID- 2306885 TI - Fatal massive pulmonary hemorrhage complicating mitral stenosis. AB - Mitral stenosis is a well known cause of hemoptysis; however, sudden death due to fatal massive pulmonary hemorrhage is an extremely rare complication. In this report, we describe a 28-year-old female with severe mitral stenosis who died suddenly due to such complication. A review of the literature shows such complication is extremely rare and unpredictable. We recommend that patients with severe mitral stenosis and history of hemoptysis be considered as candidates for early surgical intervention. PMID- 2306886 TI - Hereditary long QT syndrome in the postoperative cardiac patient. AB - The purpose of the present article is to evaluate the diagnostic implications of the long QT syndrome presenting in postoperative cardiac patients. Diagnosis of long QT syndromes may be complicated by an inability to measure the QT interval correctly due to postoperative electrocardiographic changes such as right bundle branch block. For this reason, a study of the effect of right bundle-branch block on the QT interval was undertaken. Electrocardiograms of 17 randomly selected patients undergoing a right ventriculotomy for repair of tetralogy of Fallot were evaluated for QT prolongation pre- and postoperatively. Preoperatively, no patient demonstrated QT interval prolongation. After surgery, however, right bundle-branch block created an apparent prolongation of the QT interval in 9 of the 17 patients (53%). These results suggest that in postoperative cardiac patients QT prolongation and familial long QT syndromes may be difficult to diagnose. It is, therefore, important to exclude the long QT syndrome in patients with ventricular tachycardia even if a more obvious explanation such as previous cardiac surgery is present. Usually a careful family history and preoperative electrocardiogram are all that is required. PMID- 2306887 TI - Giant P wave in a patient with right ventricular cardiomyopathy. AB - A P wave of 7.5 mm in lead I and 12.5 in V1 was detected in a 28-year-old man, with a progressive cardiomegaly since the age of 14 years. At last admission he had minor symptoms, and a systolic murmur consistent with tricuspid regurgitation. The electrocardiogram showed an extremely tall P wave and a QRS of a very low amplitude; T waves were inverted on the precordial leads. These ECG features, and subsequent investigations, were consistent with right ventricular cardiomyopathy with massive tricuspid regurgitation, and right atrial abnormality. PMID- 2306888 TI - Can coronary angiography be justified as the initial step for evaluating patients with known or suspected coronary disease? An opinion. PMID- 2306889 TI - Human immunodeficiency virus within the brains of children with AIDS. AB - Infants and children with symptomatic human immunodeficiency virus (HIV) infection frequently develop neurologic disease with symptoms and signs of acquired microcephaly, developmental delays, encephalopathy, pyramidal tract signs, and less often, movement disorders and ataxia. However, clinical courses vary and, based upon progression of neurologic findings, we have classified them into 2 broad categories; progressive (loss of previously acquired language and cognitive skills) and plateau (failure to acquire additional developmental skills). We have used immunocytochemistry to localize HIV within the brains of neurologically involved children with AIDS. Interestingly, the brains of those children with a progressive neurologic course showed readily detectable HIV antigen, while those with a plateau course showed little or no detectable HIV. These findings suggest that in children with symptomatic HIV infection, the progressive neurologic deterioration is due to continued presence of HIV within deep white matter and gray matter, while the plateau neurologic course is due to HIV induced damage followed by either limited penetration of virus into the central nervous system, or clearance of virus below detectable limits. PMID- 2306890 TI - Brain stem encephalitis in a patient with gastroduodenal and cardiovascular dysfunction: a case report. AB - The authors describe a case of a 38-year-old woman suffering from long-standing epigastric pain, abdominal fullness and vomiting due to functional alteration of gastroduodenal motility. Following a surgical procedure, a supraventricular tachyarrhythmia and hemodynamic disturbances suddenly appeared and led to death in a few hours. A histopathological study carried out on the brain stem revealed inflammatory lesions suggestive of a viral infection, whereas the study of the conduction system of the heart did not show any alterations. A clinicopathological correlation is suggested between the clinical picture and anatomical lesions of the tegmental region. PMID- 2306891 TI - Immunohistochemical demonstration of the KI-67-antigen in paraffin-embedded tumor biopsies. AB - 10 tumor specimens were processed according to a modification of the AMeX method, which allows for paraffin embedding plus immunostaining of the slices. We used this method to determine the growth fraction of tumors using the monoclonal antibody KI-67. Results were essentially the same as those obtained when studying frozen sections. The quality of the histological slices is equal to frozen sections, but greater areas of tumor can be examined. Furthermore, this method allows for compilation of a stock of tumor specimens which can be used for further immunohistochemical studies whenever needed. PMID- 2306892 TI - Multiple coarctations of the pulmonary artery: scintigraphic appearance. AB - A case of angiography-proven multiple coarctations of the pulmonary arteries is presented. The patient had a history of long-standing exertional dyspnea and intranasal cocaine use. A chest radiograph suggested oligemia in the left lung and enlargement of the right pulmonary artery, prompting ventilation and perfusion radionuclide lung imaging. The combined scintigraphic and radiographic findings were indistinguishable from those caused by pulmonary emboli. Although rare, this entity should be included in the differential diagnosis of multiple unmatched perfusion defects on pulmonary ventilation-perfusion studies. PMID- 2306893 TI - Reproducibility of radionuclide left ventricular ejection fraction in patients awaiting cardiac transplantation. AB - Radionuclide-derived left ventricular ejection fraction (LVEF) is used to assess LV systolic function, to follow trends in the natural history of dilated cardiomyopathy, and to prioritize patients waiting for cardiac transplantation. Reproducibility of LVEF at extremely low levels has not, however, been reported. To assess the reproducibility of radionuclide LVEF at levels below 0.30 EF U, 17 highly symptomatic patients (NYHA Class III/IV) with dilated cardiomyopathy were studied on two occasions, 72 hours apart. Sequential scans were analyzed by two independent observers. Mean LVEF was 0.18 +/- 0.06 U (scan 1) and 0.17 +/- 0.06 U (scan 2). Interoperator reproducibility (SD) was 0.03 U (R = 0.76), interscan reproducibility (SD) was 0.03 U (R = 0.62), and overall reproducibility (SD) was 0.04 U (R = 0.50). The interobserver variation of 0.03 (actually 0.027) was just over one half that seen in normal volunteers (variation 0.05, n = 29) studied previously in this department. A change of greater than or equal to 0.08 U (2SD) in either direction is highly likely to represent a real change in LV function in those with LVEF less than or equal to 0.30 units, compared with the change of at least 0.10 units required in those with normal LV function. Lower interobserver and interscan reproducibility should be taken into account when interpreting sequential scans in patients with severe LV dysfunction. PMID- 2306895 TI - Intracerebral uptake of Tc-99m labeled antimelanoma antibodies. AB - A patient with an intraocular tumor showed accumulation of Tc-99m labeled antimelanoma antibodies in the head. This was not due to a metastatic lesion but proved to be a benign intracranial osteoma. The reasons for this false-positive result are discussed. PMID- 2306894 TI - Iodine-131 uptake in a patient with thyroid cancer and rheumatoid arthritis during acupuncture treatment. AB - A patient with thyroid carcinoma had abnormal accumulation of I-131 in the areas of both feet and hands on whole body scan. The sites of abnormal accumulation of I-131 were similar to those on bone scintigraphy. The radiographic examination of the lesions showed characteristic findings of rheumatoid arthritis, and the presence of small gold needles for acupuncture treatment was demonstrated. There were no findings of bone metastases. Although the mechanism of accumulation of I 131 in this patient is unknown, interpreters of I-131 whole body scintigraphs should keep this case in mind when acupuncture treatment has been done. The authors can only speculate on a common blood flow mechanism for enhanced HMDP and I-131 uptake in this arthritic patient who had been treated by acupuncture. PMID- 2306896 TI - I-123 HIPDM planar brain images demonstrating crossed cerebellar diaschisis. AB - I-123 HIPDM or IMP brain planar images, as well as SPECT images, have been useful in the detection of large lesion(s) of the cerebral cortex. Planar imaging may be useful not only for cerebral lesions, but also for a cerebellar abnormality and in certain clinical situations, such as phobia to a gantry or being too heavy for the imaging table, when SPECT imaging cannot be performed. The authors concur that a large cerebral lesion can be detected by planar images; in addition, cerebellar lesions, such as the presence of crossed cerebellar diaschisis (CCD), may be detectable by planar imaging using I-123 HIPDM. This article presents a patient with a large cerebral infarct detected by planar imaging whose CCD has been demonstrated by planar images. PMID- 2306897 TI - Gallium-67 imaging in candidal esophagitis. AB - Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis. PMID- 2306898 TI - Bone densitometry of osteopetrosis in an adolescent girl. PMID- 2306899 TI - Transient nonvisualization of gallbladder in an asphyxiated neonate. PMID- 2306900 TI - Nail-patella syndrome: hereditary onchyo-osteodysplasia diagnosis by Tc-99m MDP bone scan. PMID- 2306901 TI - Epigastric vein visualization on liver scan in severe bilharzial portal hypertension. PMID- 2306902 TI - Munchausen syndrome by proxy and apnea (MBPA). A survey of apnea programs. AB - The authors sent questionnaires to 127 apnea monitoring programs asking whether they had treated patients whose apnea appeared to have been induced by a parent (Munchausen syndrome by proxy-apnea, or MBPA). Fifty-one programs (40%) reported 54 cases of this kind from among their 20,090 monitored patients (0.27%). The authors obtained further information on 32 of these patients, 83% of whom presented with infantile apnea before the third month of life. Although medical problems were documented, including apnea, the clinical condition of these infants was inconsistent with the multiple life-threatening episodes typically reported by parents. Twenty-one of the infants reportedly received cardiopulmonary resuscitation at home, 15 had ambulance calls to the home, and 24 were rehospitalized. Child Protective Service agencies were consulted for 12 patients, 5 of whom were placed in foster homes. Three index infants and five siblings are known to be dead, and one additional infant is severely brain damaged from abuse. PMID- 2306903 TI - Palpebral fissure length. In Chinese newborn infants. Comparison with other ethnic groups. AB - The palpebral fissure length was measured in 60 normal Chinese term infants in the first 48 hours of life. The measurement of the palpebral fissure length was performed with a vernier caliper by placing it across the greatest horizontal axis of the eye from the medial to the lateral canthus. The head circumference was measured by placing a tape anteriorly just above the eyebrows and posteriorly at the maximum point of the occiput. There was no difference according to sex or between the measurements in the right and the left eye. The palpebral fissure length was 1.94 +/- 0.17 cm (mean +/- standard deviation (SD)) and the head circumference was 34.0 +/- 1.3 cm (mean +/- SD). These data suggest that Chinese neonates have a shorter palpebral fissure length than do black American neonates and a longer palpebral fissure length than do white American and Turkish neonates. PMID- 2306904 TI - Chronic, episodic thrombocytopenia. A case report with long-term observation. AB - A male patient with chronic idiopathic thrombocytopenic purpura (ITP) did not fit into any of the known risk groups for chronic ITP. He was unique in that he manifested a cyclic increase of platelet counts each winter followed by a nadir in the summer, without having other hematologic abnormalities. PMID- 2306905 TI - Transient lymphoblastosis and thrombocytopenia in Gianotti-Crosti syndrome. AB - Gianotti-Crosti Syndrome, or papular acrodermatitis of childhood, represents a characteristic rash that is irregularly associated with hepatitis B infection. The authors report papular acrodermatitis in a 10-month-old child with leukopenia, thrombocytopenia, circulating lymphoblasts, and acute anicteric hepatitis B. Physical examination revealed a densely distributed papular rash on the patient's extremities and face and neck, but not on his trunk, buttocks, palms, or soles. Laboratory investigation revealed a normal bone marrow and positive hepatitis B serology. This case reinforces the fact that hematologic findings should not dissuade the work-up of papular acrodermatitis for hepatitis B or other less commonly associated viruses. PMID- 2306907 TI - Should educators accept medical jargon? PMID- 2306906 TI - Management of attention deficit hyperactivity disorder (ADHD). A continuing dilemma for physicians and educators. AB - The American Academy of Pediatrics (AAP) has recommended that the initial treatment of attention deficit hyperactivity disorder (ADHD) should be educational and behavioral. The authors surveyed the directors of special education in the United States to determine whether these services are available to children with ADHD. They determined that the diagnosis of ADHD qualifies a child for services in only 1 out of 51 departments of special education surveyed. ADHD and classroom underachievement qualifies a child for special education services in 2 out of 51 departments. Thus, in most areas of the United States, special educational services are not available to meet the guidelines of the AAP. PMID- 2306908 TI - Reactions to weaning. PMID- 2306909 TI - Hypertrophic pyloric stenosis. PMID- 2306910 TI - Cinnamon oil: kids use it to get high. PMID- 2306911 TI - Computed tomography in adult obliterative bronchiolitis. AB - Fifteen adults with obliterative bronchiolitis (OB) were investigated with computed tomography (CT). CT was considered to be abnormal in 13/15 patients (87%) showing widespread areas of increased attenuation of a patchy nature and variable proportion. CT revealed more extensive changes than the chest radiograph or bronchogram. It is a non-invasive well-tolerated and easily repeatable technique and may have an important role in the radiological evaluation of adults with OB. PMID- 2306912 TI - Role of magnetic resonance (MR) in the diagnosis and management of intracranial tuberculomas. AB - Thirty-one patients with intracranial tuberculomas were diagnosed on the basis of magnetic resonance (MR) imaging. The diagnosis was confirmed in 30; one case was a false-positive. A total of 44 tuberculomas was found in these patients of which 41 were distributed in the cerebral hemispheres, two in the brainstem and one in the cerebellum. No correlation was found between the type of lesion seen on CT and those seen on MR imaging. CT was negative in one patient with a low brainstem tuberculoma. The final diagnosis was based on the response to antituberculous drug treatment as judged by serial MR imaging in 29 patients and by biopsy in one; and one was false-positive. Thirty-nine tuberculomas, all under 2.5 cm in size, showed complete resolution after 5-8 months of treatment. The remaining five lesions were larger than 2.5 cm; four showed a 50% reduction in size after 12 months of treatment and one was completely excised. Three types of response are described to the treatment with anti-tuberculous drugs. The diagnosis of intracranial tuberculomas can be made more objectively with MR imaging. PMID- 2306913 TI - Technical development: a modified pigtail catheter for transbrachial aortography. AB - A high flow right angled 5 gauge polyethylene pigtail catheter was used in 24 patients for aorto-femoral angiography via the transbrachial approach. Its small size and right angled configuration allow easy, rapid introduction of the catheter into the abdominal aorta. PMID- 2306914 TI - Technical problem: impacted retained distal common duct stone. AB - We report a three-stage technique for use when impacted, retained distal common bile duct stones are encountered. It minimises instrumentation of the ampullary region during any one interventional session, provides drainage of biliary and pancreatic ducts between sessions and, in our opinion, maximises the chances of safely extracting such a stone. PMID- 2306915 TI - Renal excretion of enteral gastrografin in the absence of free intestinal perforation. AB - The renal excretion of orally administered water-soluble contrast medium has been described in intestinal perforation (Mori and Barret, 1962). We present a case in which orally administered Diatrizoate methylglucamine (Gastrografin, Schering) was detected in the renal collecting system on computed tomography in a man with an ischaemic segment of small bowel associated with abscess formation but no evidence of intra-peritoneal perforation. PMID- 2306916 TI - Delayed cardiac tamponade following accidental injection of non-ionic contrast medium into the pericardium. AB - A case of cardiac tamponade developing over 10 hours after accidental injection of 80 ml iohexol (350 mg i/ml) during an intravenous digital subtraction arteriography (DSA) examination is described. PMID- 2306917 TI - Gastrobronchial fistula. AB - Gastrobronchial fistula is an extremely rare condition. Trauma, subphrenic abscess and gastro-oesophageal surgery are the most commonly reported causes. We describe a case of gastrobronchial fistula occurring due to a peptic ulcer within a hiatus hernia six years following fundoplication. PMID- 2306918 TI - Clinical diagnosis from digital displays. PMID- 2306919 TI - Computed tomography of folded lung. AB - Computed tomography (CT) scans of 22 examples of folded lung in nine patients were reviewed. The most important CT criteria of folded lung are the presence of vessels and bronchi running in a smooth curvilinear fashion towards a peripheral mass with an ill defined central edge associated with pleural thickening. These features were seen in all 22 examples. The lesions are frequently multiple (eight out of nine patients). When these features are present the diagnosis can be made without recourse to biopsy or thoracotomy. Enhancement with intravenous contrast medium is unnecessary and does not provide any extra useful information. Various other previously described criteria such as air bronchograms are not necessary for the diagnosis. PMID- 2306920 TI - Primary pulmonary artery sarcoma--a report of two cases, with special emphasis on the diagnostic problems. AB - Two cases of primary sarcoma of the pulmonary artery are presented. The variable clinical and radiographic features of this rare tumour are described with particular emphasis on its ability to mimic pulmonary thrombo-embolic disease. PMID- 2306921 TI - Record release--an attorney's perspective. PMID- 2306922 TI - Medical records--sometimes you need to let go. PMID- 2306923 TI - U.S. physician gives view of the Soviet Union from Chernobyl experience. PMID- 2306924 TI - Method for assessing the probability of toxicity from drug interactions having a pharmacokinetic basis. PMID- 2306925 TI - Adenosine approved for treatment of paroxysmal supraventricular tachycardia. PMID- 2306926 TI - Caution urged in interpretation of zidovudine carcinogenicity study results. PMID- 2306927 TI - Studies reach opposite conclusions regarding role of vitamins in preventing neural-tube defects. PMID- 2306928 TI - Survey suggests Alzheimer's disease is common problem among elderly Americans. PMID- 2306929 TI - Oral betaxolol approved for once-daily therapy of hypertension. PMID- 2306930 TI - Use of intraosseous infusions in infants and children. PMID- 2306931 TI - Patient-controlled analgesia with meperidine after cesarean section. PMID- 2306932 TI - Stability of computer ECG amplitude measurements in the presence of noise. The CSE Working Party. AB - An important feature of an ECG analysis program is its ability to provide reliable measurements under various operating conditions, e.g., on noise-free and noisy ECGs. Therefore, within the European cooperative project "Common Standards For Quantitative Electrocardiography" (CSE), the accuracy and stability of ECG measurements obtained by several computer programs has been compared. To investigate the stability of measurements two sets of 10 ECGs with and without seven different high- and low-frequency types of noise--altogether 160 electrocardiograms and 160 vectorcardiograms--have been analyzed by eight electrocardiographic and five vectorcardiographic computer programs. The stability of measurement was tested with respect to results obtained for the noise-free recordings. In a previous paper, the influence of noise on wave boundary recognition has been reported. In the present paper, the effect of noise on amplitude measurements and on problems of waveform definitions within the QRS complex are described. The results indicate that programs analyzing an averaged beat exhibit less variability than programs which measure every complex or a selected beat. Comparability and stability of measurements could be improved if a standardized procedure for amplitude references were to be introduced. In addition, the stability of QRS waveform labelling could be improved if waveforms' minimum amplitude and duration were to be validated against the noise level which itself should be determined by a standardized procedure. PMID- 2306933 TI - A new method for three-dimensional reconstruction from serial sections by computer graphics using "meta-balls": reconstruction of "hepatoskeletal system" formed by Ito cells in the cod liver. AB - A new method is described for three-dimensional reconstruction from serial ultrathin sections, using "meta-balls" as a primitive of object modeling in computer graphics (CG). We take advantage of the meta-ball's blobbiness characteristic and its rendering system for reconstructing images. The two dimensional outline data from serial sections are converted into three dimensional meta-ball data with a graphic editor, "Metack," by which we can check the correctness of the data conversion. Then the converted data are visualized on a color display with a CG rendering software, "Tracy". This reconstruction method is applied in studying the spatial distribution of Ito cells (fat storing cells) in the cod liver in relation to the blood capillary. By observing the reconstructed images, we can easily understand the three-dimensional relationship between the Ito cells and the blood capillary. The Ito cells surround the blood capillary and extend their cytoplasmic processes into the inter-parenchymal space to make a well-developed network system. These findings would support a concept of "hepatoskeletal system" formed by Ito cells in the cod liver. Therefore, we think that the meta-ball reconstruction method is useful in morphological study. PMID- 2306935 TI - Connection, a microcomputer program for storing and analyzing structural properties of neural circuits. AB - The application of a microcomputer-based system (the Connection system) designed to deal with neuroanatomical information commonly analyzed by researchers and involved in the study of structural properties of neural circuits is presented. This system can be employed at first as a readily-accessible database containing physiological and anatomical data from nuclei of the central nervous system which define a network with up to 45 elements and their subdivisions and connections. Once the database from a specific network is built and stored in a file, routines of this system can be used to classify the nuclei in term of their afferents and efferents and also to display all possible pathways linking any pair of nuclei and their respective length (number of synapses). The role of such a system as an auxiliary tool in neuroanatomical and electrophysiological research is discussed by presenting the results obtained from the analysis of the neural circuits involved in cardiovascular function control in higher vertebrates. PMID- 2306934 TI - Predicting 1-year outcome following acute myocardial infarction: physicians versus computers. AB - Whether decision rules derived statistically from patient data can produce better decisions than an expert clinician or a model of the expert clinician (expert system) is controversial. We examined this issue in the context of predicting cardiac death by 1 year for patients discharged from the hospital following acute myocardial infarction. Decision rules were derived from a base sample of 781 patients. These decision rules and three experienced cardiologists then estimated probability of death by 1 year for each patient in a separate test sample (n = 400). In our evaluation of the performance of the decision rules and physicians, we detected no differences, although the decision rules and physicians tended to classify the patients somewhat differently. Further multivariate analyses on the physicians' predictions showed that two of the physicians paid attention to somewhat different variables than the third physician. Lack of agreement among expert cardiologists would complicate modeling of a consensual decision-making process within the framework of an expert system. PMID- 2306936 TI - An object oriented user interface for analysis of biological data. AB - In a previous paper we described a self-documented file and a collection of general purpose programs or tools that facilitates the management and analysis of biological data. The tools can be specified in a pipeline to accomplish a specific analysis task. However, we found that it was difficult for investigators to learn the UNIX command language for specifying pipelines, specify selection tasks through a command language, and visualize the data as they were transformed and rearranged. To alleviate these problems we developed an object-oriented user interface for the pipeline programs. The system consists of four major programs for visualization: Vedit, Vgraf, Vscan, and V spread. Vedit is a simple text editor, Vgraf is a flexible graphics program, Vscan facilitates scanning graphically through large files, and Vspread provides spreadsheet-like capabilities. To demonstrate how the visualization programs are used together to accomplish the needed analysis we describe two case studies and then discuss how well the system accomplished the goals of visualization, short learning curve, and user adaptability. PMID- 2306937 TI - Speculating with nature. PMID- 2306938 TI - Whose embryo is it? PMID- 2306939 TI - Childhood injuries in Hartford, Connecticut. AB - Vital statistics and hospital discharge data were analyzed to provide a detailed epidemiologic profile of injury among Hartford residents 0 to 19 years of age. During 1980-86, 76 death certificates identified injury as the cause of death, resulting in an annual age-specific death rate of 2.3 per 10,000 persons. Injuries caused more deaths among one to 19 year olds (58%) than all other diseases combined. During 1982-86 injury was listed as the principal diagnosis leading to hospitalization for 2,220 Hartford residents 0 to 19 years. The hospitalization rate was 95 per 10,000 persons. Injuries accounted for 16% of all hospital discharges. For ages 0 to 19, homicide was the leading injury-related cause of death accounting for 43% of fatalities. Falls were the leading cause of injury-related hospitalizations accounting for 22% if all discharges. Clay Arsenal (23%) and the Northeast (17%) neighborhoods accounted for the largest proportion of injury deaths. Actual inpatient hospital charges for 1986 were reviewed. The total cost for 420 injury discharges utilizing 2,208 hospital days exceeded $1.4 million dollars. Fifty-one percent of the injury discharges listed Medicaid as the primary expected payment source for acute care injury-related discharges. The statistical patterns identified in this report will help public health professionals establish goals for injury control efforts such as a reduction in morbidity, mortality, severity, and/or medical costs. PMID- 2306940 TI - Microvascular free-flap reconstruction of a large defect of the scalp. Experience in a community hospital. AB - The authors present a patient who had postradiation necrosis of the skull and scalp measuring over 300 cm square which was reconstructed with a free latissimus dorsi muscle flap with overlying skin grafts. The procedure was performed in a community hospital with a team comprising two plastic surgeons and a neurosurgeon, with backup from physicians assistants and nursing staff. The successful outcome of this procedure was a direct result of the concerted effort of the surgical team. We believe that microvascular free-flap reconstruction, although a complicated procedure, can be performed at the community hospital as long as appropriate measures for the care of the patient are planned and carried out. PMID- 2306941 TI - Severe neutropenia with procainamide therapy. PMID- 2306942 TI - Management of digitalis intoxicated patients following the administration of digoxin FAB antibodies (Digibind). PMID- 2306943 TI - How to comply with the Medical Waste Tracking Act of 1988. PMID- 2306944 TI - Low-level radioactive wastes. AMA Council on Scientific Affairs. AB - Under a federal law, each state by January 1, 1993, must provide for safe disposal of its low-level radioactive wastes. Most of the wastes are from using nuclear power to produce electricity, but 25% to 30% are from medical diagnosis, therapy, and research. Exposures to radioactivity from the wastes are much smaller than those from natural sources, and federal standards limit public exposure. Currently operating disposal facilities are in Beatty, Nev, Barnwell, SC, and Richland, Wash. National policy encourages the development of regional facilities. Planning a regional facility, selecting a site, and building, monitoring, and closing the facility will be a complex project lasting decades that involves legislation, public participation, local and state governments, financing, quality control, and surveillance. The facilities will utilize geological factors, structural designs, packaging, and other approaches to isolate the wastes. Those providing medical care can reduce wastes by storing them until they are less radioactive, substituting nonradioactive compounds, reducing volumes, and incinerating. Physicians have an important role in informing and advising the public and public officials about risks involved with the wastes and about effective methods of dealing with them. PMID- 2306945 TI - The right to die, as with death itself, is a private matter. PMID- 2306946 TI - A child-oriented emergency medical services system. AB - Although the principles of emergency care may be relatively easy to state, it is their promulgation that is so difficult. The development of EMS-C is the challenge. How do we take these principles of preserving children's lives and translate them into services for everyone who needs them? How do we organize a large, diverse health care system which will be responsive to this group of patients in need? How do we prioritize pediatric emergency care among the many other funding needs, both medical and nonmedical? The answer lies with the initiative and advocacy of each of us as child advocates. Providing all the aforementioned elements of the EMS-C will save children's lives. These are lives which are usually responsive to therapy, uncomplicated by interlocking disease states, and filled with potential for future achievement. The challenge is ours. PMID- 2306947 TI - T-cell paradigms in parasitic and bacterial infections. PMID- 2306948 TI - Medical aspects of torture. PMID- 2306949 TI - Tobacco trade sanctions and a smoke-free chest conference at Bangkok. PMID- 2306950 TI - Psychobiological aspects of asthma and the consequent research implications. PMID- 2306951 TI - When does bronchial arterial embolization fail to control hemoptysis? PMID- 2306952 TI - Needle aspiration in lung cancer. Risk of tumor implantation is not negligible. PMID- 2306953 TI - Perspectives on older smokers. PMID- 2306954 TI - Alterations in serum creatine kinase and lactate dehydrogenase. Association with abdominal aortic surgery, myocardial infarction and bowel necrosis. AB - Experimental studies have shown that peripheral serum creatine kinase and lactate dehydrogenase change with bowel infarction. Some clinical reports have suggested that similar changes occur in patients. This prospective study documents the changes in these enzymes associated with acute myocardial infarction, acute bowel necrosis (MES INF), and uncomplicated abdominal aortic reconstruction. Analysis of 15 patients with AMI, 13 patients undergoing major AAS, and eight patients with MES INF has shown that these conditions may be differentiated by analysis of serum CK and LD isoenzymes. The study suggests that in the absence of electrocardiographic changes, a patient with epigastric distress with elevated levels of serum CK and either CK-MB or CK-BB bands present may well have a mesenteric rather than a myocardial infarction. Acute myocardial infarction can be ruled out further through analysis of serum LD1/LD2 ratios. PMID- 2306955 TI - Bronchial hyperresponsiveness in patients with chronic congestive heart failure. AB - To investigate the relationship between pulmonary congestion and bronchial responsiveness, we measured bronchial responsiveness to acetylcholine in 51 patients with left heart disorders. The measurement of bronchial responsiveness was performed by inhaling doses of acetylcholine chloride (0.08 to 20 mg/ml) and calculating the PC20-FEV1. The median value for PC20-FEV1 was above 20 mg/ml in the subjects without history of congestive heart failure (n = 18), was 5.29 mg/ml in the subjects with clinical evidence of congestive heart failure in the past days (n = 18; p less than 0.01), and was 5.74 mg/ml in the subjects with clinical evidence of congestive heart failure at the time of study (n = 15; p less than 0.01). The hemodynamic variables by cardiac catheterization and the clinical symptoms were not correlated with the grade of bronchial responsiveness. These results suggest that the bronchial responsiveness was increased in most of the patients with chronic congestive heart failure. We concluded that continuous pulmonary congestion may contribute to the pathogenesis of bronchial hyperresponsiveness. PMID- 2306956 TI - Pneumothorax following transbronchial biopsy. Low diagnostic yield with routine chest roentgenograms. AB - A chest roentgenogram is commonly obtained after a transbronchial biopsy to exclude a pneumothorax. We hypothesized that these routine chest roentgenograms rarely demonstrate a pneumothorax in patients who have neither symptoms nor fluoroscopic findings of lung collapse. To test this hypothesis, we studied 305 consecutive patients undergoing bronchoscopy with fluoroscopically guided TBB. No patient without symptoms and fluoroscopic findings suggesting lung collapse had a pneumothorax demonstrated on the post-biopsy chest roentgenogram. At the University of Virginia, routine chest roentgenograms failed to demonstrate a single unsuspected pneumothorax among all patients undergoing TBB during a period of nearly six years. Given this low incidence of unsuspected pneumothorax, we conclude that routine chest roentgenograms have a low diagnostic yield and may not be necessary in all patients after fluoroscopically guided TBB. PMID- 2306957 TI - Recurrent bleeding after arterial embolization in patients with hemoptysis. AB - Thirty-three patients with hemoptysis caused by nonmalignant diseases underwent arterial embolization. In seven (21.2 percent) of 33 patients, hemoptysis recurred after initial embolization in a follow-up period ranging from one day to four years. Although there was no difference in age and daily quantity of bleeding among patients with and without recurrences, those with mycetoma suffered the highest recurrence of bleeding after initial embolization (three [75 percent] of four patients). In the initial arteriograms of the seven patients were found six cases of markedly increased vascularity, three of increased vascularity in the bilateral lung, and three of nonbronchial systemic arterial supply to the diseased lung. Of six patients who received reexamination at the time of recurrent bleeding, the arteriogram demonstrated recanalization of previously embolized artery in five and revascularization by collateral circulation in five. In addition, hemoptysis recurred in three (60 percent) of five patients after second embolization and in one (50 percent) of two after third embolization. Four patients underwent surgical therapy: two after the initial embolization, one after the second, and one after the third, and these patients had no recurrence. While arterial embolization as initial treatment of hemoptysis is a highly useful procedure, this is a palliative procedure and potential for recurrence of hemoptysis exists as the lesion that has initially caused hemoptysis is not cured by the embolization. We emphasize that a combination therapy of repeated embolization and surgery will probably improve the efficacy of treatment of recurrent bleeding after initial embolization. PMID- 2306958 TI - The older smoker. Status, challenges and opportunities for intervention. AB - Smoking is a significant cause of morbidity and mortality among older adults. Cessation of smoking benefits older adults almost immediately. Little is known, however, about how older adults quit and how to help them. No smoking cessation programs have been designed for this population. Here we report the findings of a random survey of American Association of Retired Persons members conducted to learn more about older smokers, their smoking and health characteristics, their quitting motivations and experiences, and the role of physicians' advice to quit. We obtained data on 339 current smokers aged 50 to 102. Current smokers were more likely to be heavy, highly addicted smokers. They also reported more smoking related symptoms and conditions and fewer preventive tests and check-ups than never-smokers or former smokers. Although 44 percent of smokers were interested in quitting, only 39 percent reported that they had been advised to stop smoking by their physicians in the previous year. Physicians who treat older patients can have a significant impact on helping them to stop smoking by giving them a strong recommendation to quit and by providing appropriate interventions. PMID- 2306959 TI - R- and S-wave amplitude changes with acute anterior transmural myocardial ischemia. Correlations with left ventricular filling pressures. AB - The value of R- and S-wave amplitude changes as electrocardiographic (ECG) markers of myocardial ischemia and dysfunction was evaluated using coronary angioplasty as a model of acute transmural ischemia and ST segment elevation. Hemodynamic data and 12-lead ECGs were recorded at baseline and during coronary occlusion in 34 patients with left anterior descending artery angioplasty. In the precordial leads V1 through V4, the sum of R-wave amplitude increased in 17 patients, was unchanged in ten, and decreased in seven; the sum of S-wave amplitude decreased in 33 patients (including two patients with complete loss of S wave) and increased in one. Mean R-wave change was 2.7 +/- 6.2 mm, mean S-wave change was -12.9 +/- 9.0 mm, and mean precordial ST elevation was 12.5 +/- 8.7 mm. Absolute R-wave change correlated directly with ST elevations (p = .013), while S-wave change correlated inversely (p less than .007). Only ST elevations correlated with changes in pulmonary capillary wedge pressure (PW) (p less than .007). In the precordial lead with maximum ST elevations, only R-wave changes correlated with ST elevations (p = .002), and both R-wave changes and ST elevations correlated with changes in PW (R:p = .027; ST:p = .007). The presence of large increases in R waves or decreases in S wave, or of high-magnitude ST elevations identified patients with the highest elevations in PW. In conclusion, decreases in S waves and, less commonly, increases in R waves are seen with diagnostic ST elevations and may have some limited clinical value. The correlation between magnitude of acute anterior ST elevations and changes in left ventricular filling pressures may have important clinical consequence. PMID- 2306960 TI - Right chest electrocardiographic patterns in normal subjects. AB - Right-sided chest lead ECGs (V3R to V6R) were recorded in 110 normal male subjects who were between the ages of 17 and 22 years old (mean, 17.9 years). The prevalence of the rS pattern decreased from V3R (89 percent) to V6R (37 percent). However, the opposite was the case for the rSr pattern (10 percent in V3R and 36 percent in V6R). The amplitudes of the r wave, S wave and secondary r wave all progressively decreased from V3R to V6R. The prevalence of the qr and qS patterns was 0 and 1 percent, respectively in V3R and 14 and 2 percent, respectively in V6R. A positive ST segment deviation of 0.5 to 1 mm was present in 13 percent of subjects in V3R and 5 percent in V4R. T wave inversion was common and the prevalence increased from V3R (60 percent) to V6R (79 percent). PMID- 2306961 TI - Diagnostic fiberoptic bronchoscopy and protected brush culture in patients with community-acquired pneumonia. AB - A model for performing fiberoptic bronchoscopy as a supplement to noninvasive diagnostic methods, in patients with community-acquired pneumonia, was prospectively studied. Twenty-four patients underwent bronchoscopy, seven pilot patients and 17 of 277 (6 percent) consecutive patients with CAP. Indications for FOB were early therapy failure (less than or equal to 72h)(n = 7), late therapy failure (greater than 72h)(n = 11), or before start of antibiotic therapy in severely ill or immunocompromised patients (n = 6). Samples were obtained by aspiration of bronchial secretion and with a protected brush catheter from which quantitative cultures with a detection level of 10(4) colony forming units per ml were performed. Results concluded that FOB, with the use of quantitative PB cultures, offered a safe and specific diagnostic tool, which on special indications, can be of great value in the management of patients with CAP. PMID- 2306962 TI - Persistent hypoxemia and excessive daytime sleepiness in chronic obstructive pulmonary disease (COPD). AB - Fourteen patients with chronic obstructive pulmonary disease (COPD) and chronic hypoxemia were studied to evaluate the relationship between hypoxemia and objective and subjective daytime sleepiness. Patients were selected with a waking PaO2 of less than 70 mm Hg and less than 50 percent predicted FEV1. Clinically, none of these patients had complaints of significant daytime sleepiness. Each patient underwent standard all-night polysomnographic evaluation followed by a multiple sleep latency test (MSLT). There was no significant correlation between the mean sleep onset latency for the MSLT and the waking PaO2, PCO2, FEV1, or spontaneous desaturations during sleep. Patients with COPD exhibited a mean MSLT that was within normal limits, despite a short total sleep time and numerous arousals from sleep. We conclude that there appears to be no relationship between chronic daytime hypoxemia and subjective reports and objective measures of daytime sleepiness. PMID- 2306963 TI - Smell and taste function in subjects with chronic obstructive pulmonary disease. Effect of long-term oxygen via nasal cannulas. AB - It was hypothesized that subjects with chronic obstructive pulmonary disease (COPD) receiving long-term oxygen via nasal cannulas have an impaired sense of smell and/or taste. To objectively evaluate the sense of smell and taste, this study used the University of Pennsylvania Identification Test (UPSIT), a 40-item "scratch-n-sniff" test and a 20-item taste test using the four basic taste sensations of sweet, salt, sour, and bitter. Twenty subjects (15 male, 5 female) with severe COPD receiving long-term oxygen therapy (group 1), and an equal number of age- and sex-matched subjects with COPD not receiving oxygen therapy (group 2), and a healthy control group (group 3) were studied. Twelve subjects (seven male, five female) from group 1 subsequently underwent transtracheal oxygen catheter installation. Mean +/- SD for the basic smell test was significantly greater in group 3 (35.35 +/- 3.58) as compared with group 1 (27.70 +/- 6.07) or group 2 (31.10 +/- 4.95) (p less than 0.005). The difference between group 1 and 2 was not significant (p = 0.066). However, when adjusted for pack years of smoking, there were no significant differences between the three groups. Mean +/- SD correct responses for the basic taste test were significantly greater in group 3 (15.75 +/- 1.81) as compared with group 2 (12.8 +/- 2.78) (p less than 0.005) and group 1 (14.00 +/- 2.33) (p less than 0.05). There was no significant difference between group 1 and 2. The corrected data for taste, adjusted for years since quitting smoking, did not alter the basic differences between the groups. Mean smell and taste test scores were essentially unchanged in 12 subjects after six months of transtracheal oxygen therapy. Long-term oxygen use via nasal cannulas in this group of subjects with COPD did not appear to impair their sense of smell and taste. Smoking had a significant but variable effect on the sense of smell and taste. PMID- 2306964 TI - Comparison of flow-resistive work load due to humidifying devices. AB - There are many kinds of humidifying devices. We evaluated six humidifiers from the viewpoint of AWLs. The AWL was obtained by calculating the area difference between pressure-volume tracings obtained without and with humidifiers. To examine the effect of pressure monitoring sites on AWL when a humidifier is placed, we measured AWL at three different pressure monitoring sites. The AWL was affected significantly by the pressure monitoring site for the ventilator. When a pressure monitor sensor was placed on the inspiratory limb between the inspiratory valve and humidifiers, the ventilator was not able to compensate for the pressure drop caused by impedance characteristics of the humidifier equipment. This resulted in significant inspiratory AWL on the patient. Thus, humidifying devices should be carefully selected from the viewpoint of not only humidifying capability but also AWL. Furthermore, we must recognize the importance of the pressure monitoring site for the ventilator. PMID- 2306965 TI - Variation in maximum inspiratory and expiratory pressure after application of inspiratory loads in patients with COPD. AB - We studied eight men with chronic obstructive pulmonary disease (COPD) (age, 60.57 +/- 7.59 years; height, 162 +/- 10.43 cm; weight, 65 +/- 9.7 kg). Functional values of the sample were as follows: FEV1, 46 percent; FVC, 67 percent; PO2, 72.4 mm Hg; and pH, 7.41. We used a modification of the Nickerson and Keens method. Patients were required to perform 65 percent of maximal inspiratory pressure (MIP). We counted the time from the start of the test to exhaustion of the patient (TLIM). We measured basal MIP and maximal expiratory pressure (MEP) (TLC) at the TLIM and 10, 20, and 30 minutes and MIP was different from the basal value (MIP basal, 85.7 cm H2O; MIP 10 minutes, 79.1 cm H2O; MIP 20 minutes, 78.6 cm H2O; MIP 30 minutes, 79.6 cm H2O. The MEP was not different from the basal value. We concluded that in patients with COPD, MIP decreases significantly after inspiration through umbral inspiratory weight equal to 65 percent MIP and does not return to basal value for 30 minutes. The MEP does not change with respect to basal determination. PMID- 2306966 TI - Pentoxifylline improves pulmonary gas exchange. AB - Pentoxifylline is a xanthine derivative with hemorrheologic and vascular properties that may improve gas exchange in patients with chronic obstructive pulmonary disease (COPD). We tested this hypothesis in 12 patients with COPD (mean FEV1 = 40 percent predicted; mean DCO, 8.6 ml/min/mm Hg) randomly divided into a treatment and control group and six healthy volunteers. Following establishment of baseline DCO and maximum expiratory flow volume (MEFV) curve values, each subject in the treatment and healthy groups took 400 mg of pentoxifylline three times a day for 12 weeks. Weekly DCO and MEFV curves were measured before treadmill exercise in both COPD groups and before and after exercise in the healthy group. The MEFV curve parameters from the final three weeks of therapy did not differ significantly from baseline values. During this time, however, the treatment COPD group's resting DCO rose by 8.2 +/- 2.4 percent over baseline level (p less than 0.01). Treadmill walk time increased from 17.7 +/- 2.9 minutes to 23.2 +/- 2.9 minutes (p less than 0.02). This was accompanied by improved exercise oxygen saturation measured by oximetry (SoxiO2). Premedication SoxiO2 fell from 92.8 +/- 1.2 percent to 88.6 +/- 2.5 percent during exercise, and from 94.4 +/- 1.1 percent to only 91.8 +/- 1.0 percent after 12 weeks of medication (p less than 0.05). No such improvement was noted in the control COPD group. Although the healthy group's resting SoxiO2 and DCO did not change during treatment, their exercise DCO increased significantly from 36.3 +/- 3.1 ml/min/mm Hg to 41.8 +/- 3.5 ml/min/mm Hg (p less than 0.001). These data demonstrate that pentoxifylline improves gas exchange, possibly by increasing cardiac output, and/or by raising mixed venous PO2, and/or by improving blood flow to underperfused alveoli. PMID- 2306967 TI - Increases in HLA-DQ, DP, DR, and transferrin receptors on alveolar macrophages in sarcoidosis and allergic alveolitis compared with fibrosing alveolitis. AB - We have used flow cytometric methods to detect and quantify HLA-DR, DQ, and DP antigens and transferrin receptors on alveolar macrophages in lavage samples from 36 patients with granulomatous lung diseases (extrinsic allergic alveolitis [EAA], n = 13; sarcoidosis, n = 23), and 12 patients having fibrosing alveolitis (FA) (cryptogenic fibrosing alveolitis, n = 3; FA and scleroderma, n = 8; FA and primary biliary cirrhosis, n = 1). HLA-DR, DQ, and DP antigens were expressed on the majority of alveolar macrophages in all the patients, and the percentages of positive cells were similar to those in control subjects without lung disease. However, the amounts expressed were higher in those with EAA and sarcoidosis than in the FA group or control subjects, the most significant differences being in HLA-DQ and HLA-DP expression. Transferrin receptor expression was also higher in the granulomatous lung diseases. In sarcoidosis, higher levels of HLA-DQ correlated with lower lung function measurements (Dco p less than 0.025, FVC p less than 0.025, FEV1 p less than 0.005), suggesting this may be a marker of disease activity. HLA-DP levels also showed a trend (p less than 0.1) of inverse correlation with lung function. Levels of HLA-DQ (p less than 0.005) and HLA-DP (p less than 0.001) correlated more closely than HLA-DR with numbers of lymphocytes in the lavage fluids, and HLA-DQ levels correlated with increasing proportions of lymphocytes in proliferation (p less than 0.05). We suggest that high levels of HLA-DQ and DP on alveolar macrophages may be more relevant than HLA-DR to the enhanced antigen-presenting function of these cells in sarcoidosis, and possibly also in EAA. PMID- 2306968 TI - Effect of endobronchial radiation therapy on malignant bronchial obstruction. AB - We evaluated the effect of endobronchial radiation therapy in 52 patients with malignant airway occlusion. Fifty-five endobronchial applications of the radioisotope iridium 192 were carried out. Response was assessed by change in performance status, symptom resolution, duration of symptom relief, roentgenographic reaeration, pulmonary function tests, and postimplant bronchoscopy. Thirty-three patients showed at least a one-level improvement in performance status. Of a total of 166 symptoms present prior to therapy, 131 resolved or improved. Approximately 70 percent of a patient's lifetime was rendered symptom improved or symptom free. A roentgenographic reaeration response of 30/41 (73 percent) was achieved. The average FEV1 and FVC improved from 1.5 to 2.1 L and from 2.3 to 2.9 L, respectively. Posttherapy bronchoscopy was performed between one and two months following the implant in 15 patients who agreed to undergo the procedure. Eleven (73 percent) of 15 had complete tumor regression. Major long-term complications were noted in seven patients. Endobronchial radiation, therefore, appears to be a safe and effective technique to palliate malignant airway occlusion. PMID- 2306969 TI - Fluconazole in the treatment of persistent coccidioidomycosis. AB - Fluconazole is one of the new antifungal triazoles undergoing clinical trials. We used fluconazole at a dose of 50 or 100 mg/day in an open trial for the treatment of patients with persistent coccidioidomycosis. Fourteen patients were enrolled and treated for a mean of 13 +/- 7 months. Two failed to respond. Of the 12 who responded, one reactivated while being treated, and one died of myocardial infarction after successful treatment of his fungal infection; six had relapses from nine days to 15 months after treatment was stopped. Only four patients are asymptomatic at a mean of 14 +/- 3 months after cessation of treatment. Fluconazole is well tolerated at this dose. In view of its low toxicity, the partial clinical efficacy observed, and the high recurrence rate of chronic coccidioidal infection, it would be justified to try higher doses. PMID- 2306970 TI - Physiologic effects and side effects of prostaglandin E1 in the adult respiratory distress syndrome. AB - Because PGE1 previously has been reported to increase survival of patients with ARDS, we evaluated physiologic effects and side effects of PGE1 in a prospective open-label study of patients with ARDS. Seventeen patients with ARDS who did not have significant renal or hepatic dysfunction received PGE1 by continuous central venous infusion (30 ng/kg/min). Seventeen control patients with ARDS without renal or hepatic dysfunction who had similar APACHE II and ARDS scores and causes of ARDS did not receive PGE1. Prostaglandin E1 significantly decreased the SVRI and oxygen extraction ratio. Concentrations of total and polymorphonuclear leukocytes, but not platelets, increased significantly during PGE1 infusion, but did not change in control patients. There was no change in the Do2I and Vo2I during the course of the PGE1 infusion. There were no differences in Do2I and Vo2I during PGE1 infusion between survivors and nonsurvivors. Prostaglandin E1 was infused for a mean of 5.9 +/- 1.8 days (+/- SD) and was discontinued on ten occasions in seven patients because of supraventricular dysrhythmias (n = 4), hypotension (n = 3), thrombocytopenia (n = 3), and cardiac arrest (n = 2). Nonsurvivors had PGE1 discontinued prematurely more frequently than survivors (56 percent [5/9] vs 25 percent [2/8], respectively). The prevalence of multiple system organ failure and the in-hospital mortality of both PGE1-treated and control patients were not different. Although PGE1 causes significant systemic vasodilation and possibly decreased intrapulmonary polymorphonuclear leukocyte sequestration, PGE1 does not influence multiple-system organ failure or mortality of patients with ARDS without renal or hepatic dysfunction. PMID- 2306971 TI - Continuous nebulization of albuterol (salbutamol) in acute asthma. AB - We studied the safety and efficacy of albuterol (salbutamol) delivered by continuous nebulization (CN) in the initial emergency department treatment of asthma. In a randomized fashion 21 patients received 5 mg of albuterol by bolus nebulization (BN) at time 0 and again 60 minutes later. Twenty-one others received albuterol (0.2 mg/ml) by CN using a calibrated nebulizer with a known output of 25 ml/h. Thus, each patient had received 10 mg of albuterol over two hours. FEV1, blood pressure (BP), heart rate (HR), respiratory rate (RR), and hand tremor were recorded at 30-minute intervals. The FEV1 was 1.48 +/- 0.64 L prior to BN and increased to a maximum of 2.20 +/- 0.94 L (p less than 0.05) 90 minutes later. The FEV1 prior to CN was 1.13 +/- 0.51 L and improved to 2.20 +/- 1.02 L (p less than 0.05) at 120 minutes. The FEV1 did not differ significantly between regimens over the 2-hour period. Both modes of therapy were well tolerated. There was a slight but significant increase in HR at 30 and 90 minutes in the BN group when compared with CN. There was no significant difference in BP, RR, or tremor between the groups. Thus, albuterol by CN was found to be equally effective as the same medication by BN in the early treatment of asthma in patients seen in the emergency department. PMID- 2306972 TI - Isoflurane therapy for status asthmaticus in children and adults. AB - Two adults and two children with life-threatening asthma refractory to maximal standard therapy were treated with the inhalational anesthetic agent isoflurane. In each case, the temporal response to the initiation of therapy was striking. All patients survived and none experienced adverse reactions attributable to the drug. Rapid therapeutic benefit, minimal side effects, absence of cumulative toxicity, and ease of administration are factors supporting the use of isoflurane for patients with severe asthma. PMID- 2306973 TI - Aggressive intensive care treatment of very elderly patients with tetanus is justified. AB - Tetanus is now rare in industrialized countries, occurring mainly in elderly patients. To assess whether aggressive therapy of these patients in the intensive care unit is justified, we retrospectively studied all patients with tetanus hospitalized in our institution between 1968 and 1989. Patients over the age of 70 years fared as well as those under 70 years and recovered without sequelae. These results favor aggressive treatment of elderly patients with tetanus in the intensive care unit. PMID- 2306974 TI - Postoperative pneumothorax. Real or pseudo? Gastrothorax simulating postoperative pneumothorax. PMID- 2306975 TI - Immediate drainage is not required for all patients with complicated parapneumonic effusions. AB - We retrospectively investigated if the clinical course of complicated parapneumonic effusions was altered by treatment with immediate drainage plus antibiotics vs antibiotics alone. The two groups of patients had no significant differences in age, duration of symptoms prior to hospitalization, initial maximum temperature, WBC count, or characteristics of the pleural fluid. There were no differences in the duration of hospitalization, fever, elevated WBC count, intravenous antibiotic therapy, or the time for roentgenographic resolution of the effusions. There was one death in each group. The infection of the pleural space resolved in 13 of 16 patients treated with antibiotics alone. No recurrence of the infection of the pleural space occurred in these patients. Antibiotics alone were not sufficient in two cases which eventually required chest tube drainage. Therefore, not all complicated parapneumonic effusions require drainage. A prospective study is required to determine if chest tube drainage should be part of the initial management of complicated parapneumonic effusions. PMID- 2306976 TI - The pathophysiology of carbon monoxide poisoning and acute respiratory failure in a sheep model with smoke inhalation injury. AB - A smoke inhalation model was created in 22 adult male sheep with pine smoke inhalation through an endotracheal tube for 6 min. Arterial blood gases, HbCO, HbO2 and pulmonary compliance (Cdyn) were monitored, and the morphology of the tracheobronchial tree and pulmonary parenchyma were studied by light and electron microscopy. Severe carbon monoxide poisoning with fatal levels of HbCO (greater than 50 percent) was found at the end of smoke inhalation. Acute respiratory distress, progressive hypoxemia, decreased pulmonary compliance and increased P(A a)O2 and Qs/QT occurred after injury. Tracheobronchial blockade by pseudomembrane cast, pulmonary edema, atelectasis and necrosis of pulmonary epithelia were demonstrated pathologically. The mechanisms of CO poisoning and ARF are discussed. PMID- 2306977 TI - Yellow nails, lymphedema and pleural effusion. Treatment of chronic pleural effusion with pleuroperitoneal shunting. AB - Pleural effusion secondary to lymphedema may be chronic, symptomatic and refractory to treatment, occasionally requiring invasive and painful procedures such as chemical pleurodesis, open pleural abrasion or pleurectomy to achieve control of the effusion and gain symptomatic relief. We report a patient with yellow nail syndrome and chronic pleural effusion successfully treated with pleuroperitoneal shunting. PMID- 2306978 TI - Anomalous inferior vena cava with azygos continuation, dysgenesis of lung, and clinically suspected absence of left pericardium. AB - We report a case of anomalous continuation of the inferior vena cava with azygos vein, defect of left pericardium, and dysgenesis of lobes of the lungs. A 43-year old man came to our hospital, complaining of dyspnea and cough with blood in the sputum. The chest roentgenogram showed moderate cardiomegaly with deviation to the left side of the thorax. Therapy with diuretics and bronchodilators reduced his complaints. A bronchogram and fiberoptic bronchoscopy showed double bronchial branches to the right upper lobe, one from the trachea and the other from the right main bronchus, and a blind pouch of the left lobe. Thoracic computed tomography showed the heart just behind the sternum. Venography showed anomalous continuation of the inferior vena cava and dilated azygos vein. We could not find such a complicated anomaly of the thoracic vessels and bronchus in an adult in the literature, so we believe that it is important to reconfirm the position of major vessels or organs before a thoracic procedure. PMID- 2306979 TI - Chronic pleural effusion following coronary artery revascularization with the internal mammary artery. AB - Two patients developed chronic symptomatic pleural effusions following coronary artery revascularization with the IMA. Both patients had evidence of left ventricular dysfunction and pleural effusions which only involved the side corresponding to the harvested IMA. PMID- 2306980 TI - Perforated aneurysm of the anterior mitral valve. A Doppler and two-dimensional echocardiographic report. AB - Antemortem diagnosis of a perforated MV aneurysm by Doppler echocardiography, as well as two-dimensional echocardiography (2-DE), has not been reported. Herein we present such a case. PMID- 2306981 TI - Systemic embolization following thrombolytic therapy for acute myocardial infarction. AB - We describe a patient with acute inferior myocardial infarction who developed a "saddle" aortic embolus during streptokinase infusion. Three months previously, this patient had sustained an anterior infarction, and an apical aneurysm was found. This patient's embolus had most probably originated from a left ventricular mural thrombus that had been dislodged by streptokinase. As fibrinolytic treatment is gaining wide acceptance, physicians should be aware of this rare, but possible, complication. PMID- 2306982 TI - Tension pneumothorax complicating small-caliber chest tube insertion. AB - We report two patients who developed tension pneumothorax as a result of improper attachment of a Heimlich valve to a chest tube. PMID- 2306983 TI - Cardiac pheochromocytoma originating in the interatrial septum. AB - A 36-year-old woman with classic clinical and biochemical features of pheochromocytoma was found to have a cardiac pheochromocytoma originating in the interatrial septum and a significant obstructive lesion in the left anterior descending coronary artery. Complete resection of the pheochromocytoma and an aortosaphenous vein graft were performed. This is the first reported case of successful resection of an interatrial pheochromocytoma. PMID- 2306984 TI - Diagnosis of tracheopathia osteochondroplastica. PMID- 2306985 TI - Sleep apnea, hypothyroidism and pulmonary edema. PMID- 2306986 TI - An earlobe lesion and a lung nodule. PMID- 2306987 TI - Doppler evaluation. PMID- 2306988 TI - Morphology of ductus arteriosus and of the pulmonary arteries in patients with pulmonary atresia and complex congenital heart disease. PMID- 2306989 TI - Diagnostic value of carcinoembryonic antigen in bronchoalveolar lavage fluid of peripheral lung cancer. PMID- 2306990 TI - Chest roentgenograms. PMID- 2306991 TI - Endobronchial metastasis from Hurthle cell thyroid carcinoma. PMID- 2306992 TI - Effects of theophylline (T) on diaphragmatic contractility in dogs. PMID- 2306993 TI - Histopathologic effect of corticosteroids on respiratory muscles in the rabbit. PMID- 2306994 TI - The effects of short- and long-term corticosteroid treatment on rat diaphragm contractility and fatigue. PMID- 2306995 TI - Home care rehabilitation and perception of dyspnea in chronic obstructive pulmonary disease (COPD) patients. PMID- 2306996 TI - Lung transplantation for end-stage pulmonary disease. Effects of donor lung size on pulmonary function. PMID- 2306997 TI - Single-lung transplantation in hyperinflated patients. PMID- 2306998 TI - Negative-pressure ventilation improves respiratory center drive in patients with chronic obstructive pulmonary disease (COPD). PMID- 2306999 TI - 32nd annual Aspen Lung Conference: Chronic respiratory failure. Proceedings. PMID- 2307000 TI - Contribution of rib cage and abdominal expiratory muscles to tidal volume in head up dogs. PMID- 2307001 TI - Neck and pectoral girdle muscle contribution to intrathoracic pressure. PMID- 2307002 TI - Inspiratory reflexes in diabetes mellitus. PMID- 2307003 TI - Mechanism of detection of added respiratory loads. PMID- 2307004 TI - The respiratory and vascular responses evoked by chemical activation of small fiber phrenic nerve afferents in dogs. PMID- 2307005 TI - Electromyographic response of the diaphragm to a sudden increase in operating length. PMID- 2307006 TI - Comparison of zolpidem (Z), triazolam (T), and flunitrazepam (F) effects on arterial blood gases and control of breathing in patients with severe chronic obstructive pulmonary disease (COPD). PMID- 2307007 TI - Differential activation of respiratory muscles by CO2 and hypoxia in man. PMID- 2307008 TI - Carotid bodies and expiratory muscle recruitment. PMID- 2307009 TI - Hypoxic exposure and activation of the after-discharge mechanism. PMID- 2307010 TI - Role of inspiratory muscle dysfunction in chronic hypercapnia. PMID- 2307011 TI - Factors determining the pattern of ventilatory muscle recruitment (VMR) in patients with chronic obstructive pulmonary disease (COPD). PMID- 2307012 TI - Effect of lung volume and respiratory impedance on transdiaphragmatic pressure and muscle tension in dogs. PMID- 2307013 TI - Hyperinflation is associated with reduced strength and efficiency of the respiratory muscles in asthmatic and normal subjects. PMID- 2307014 TI - Incidence and clinical correlates of nocturnal awakening secondary to dyspnea in chronic obstructive airway disease (COAD). PMID- 2307015 TI - Pulmonary artery pressure during sleep apnea. PMID- 2307016 TI - Right ventricular pressure/volume relationship at rest and during exercise in patients with chronic lung disease. PMID- 2307017 TI - Interaction of O2 and CO2 on respiratory drive (RD) in severe chronic obstructive pulmonary disease (COPD). PMID- 2307018 TI - A possible role for mixed venous blood changes in the hyperventilation of exercise in heart-lung transplant recipients. PMID- 2307019 TI - Effect of chronic malnutrition on rat diaphragm contractility and fatigue. PMID- 2307020 TI - Effects of inspiratory loading on 31phosphorus magnetic resonance (PMR) spectroscopy of the inspiratory intercostal muscles in normal humans. PMID- 2307021 TI - Maximal inspiratory pressure in respiratory failure. PMID- 2307022 TI - Intracellular oxidant production by isolated diaphragm. PMID- 2307023 TI - Aminoglycoside dosing regimen and pharmacokinetic parameters in the guinea pig. AB - To complement a study on aminoglycoside dosing regimen and ototoxicity in the guinea pig, we designed an experiment to examine: (1) the effect of dosing regimen on guinea pig pharmacokinetic parameters, and (2) possible differential accumulation after repeated intramuscular administrations of netilmicin and amikacin (150 mg/kg/day) for 7 days by 1 or 3 daily injections. The area under the curve (AUC infinity) and the maximum plasma concentration (Cmax) were dose dependent. Within each regimen, no significant difference was observed between days 1 and 7. Little or no accumulation was observed after 21 days of treatment. The results show a good dose-dependence of AUC infinity and Cmax and are in accordance with data from human studies. Moreover, the fact that no accumulation occurred in the guinea pig suggests that it is a suitable animal model to evaluate the relation between aminoglycoside ototoxicity and dosing regimen. PMID- 2307024 TI - Relation of dosing regimen to aminoglycoside ototoxicity: evaluation of auditory damage in the guinea pig. AB - Groups of guinea pigs were injected intramuscularly for 21 days with netilmicin or amikacin 150 mg/kg/day by one or three daily injections. Amikacin was also tested at 225 mg/kg/day with each dosing regimen. Auditory function was evaluated during the experiment by reflexological and electrophysiological tests. Morphological damage to the inner ear was also evaluated. Netilmicin had no effect on the auditory function nor did it damage the organ of Corti. Conversely, amikacin impaired the auditory function and produced loss of hair cells in a dose related manner. The effect was equally marked with both dosing regimens of 225 mg/kg/day, whereas a slight decrease of auditory impairment was observed with 150 mg/kg administered once a day. The data suggest that administration of a single daily dose of aminoglycosides does not increase the risk of ototoxicity specifically associated with each compound. PMID- 2307025 TI - Triple combination of retinoic acid, low concentration of cytarabine and dimethylformamide induces differentiation of human acute myeloid leukaemic blasts. AB - Differentiation induction therapy provides an alternative for treatment of patients with acute myeloid leukaemia (AML) who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + low concentration of cytarabine (Ara-C) + dimethylformamide (DMF) on the differentiation of blasts from 24 AML patients was studied. Nonadherent mononuclear cells were cultured at a concentration of 5 x 10(5) cells/ml in 24-well tissue culture plates containing RPMI 1640 culture medium with 20% fetal calf serum, 10% autologous serum and 10% 5637-conditioned medium and incubated with 10(-6) M RA, 10(-6) M Ara-C and/or 100 mM DMF alone and in combination with each other for 6 days in primary culture at 37 degrees C in a humidified incubator under 5% CO2. The triple combination of 10(-6) M RA + 10(-6) M Ara-C + 100 mM DMF induced 90% of blasts from 22 out of 24 AML patients to differentiate. These highly effective results justify a clinical trial of this triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. PMID- 2307026 TI - Randomized comparison of ofloxacin and doxycycline for chlamydia and ureaplasma urethritis and cervicitis. AB - Fifty-eight males and 34 females with nongonococcal urethritis and/or cervicitis were treated to compare the efficacy and safety of 7-day regimens of oral ofloxacin 300 mg twice daily and doxycycline hyclate 100 mg twice daily. Forty seven patients were randomized to receive ofloxacin and 45 patients to receive doxycycline. The microbiologic response rate was 97% (32/33) for both ofloxacin and doxycycline; the combined microbiologic and clinical cure rates were 98% for both treatment groups (ofloxacin 46/47, doxycycline 44/45). Ofloxacin was as effective as doxycycline in the treatment of chlamydial infections (96% vs. 100%). In patients with Ureaplasma urealyticum, the initial response was complete with either drug, but recurrence of infection was observed with both treatment groups (1 of 4 patients in the ofloxacin group and 2 of 11 patients in the doxycycline group). In the treatment of mixed Chlamydia trachomatis and U. urealyticum infections, all 5 patients treated with ofloxacin and 3 of 4 patients treated with doxycycline were cured. In symptomatic patients whose initial cultures were negative, clinical cures were complete with both drugs, but Ureaplasma was isolated at 3 or more weeks post-treatment in 2 patients treated with ofloxacin. In a study of single-dose ofloxacin treatment of uncomplicated gonorrhea, Neisseria gonorrhoeae was eradicated in all subjects, but C. trachomatis was not reliably eradicated. Both drugs were well tolerated with only minimal adverse effects reported in either treatment group. A multiple-dose regimen of ofloxacin appears to be a highly effective and well-tolerated alternative to doxycycline in nongonococcal sexually transmitted disease. PMID- 2307027 TI - Evaluation of a controlled-released membrane infusion device for delivery of gentamicin. AB - A new controlled-release membrane infusion device has been developed which consists of a drug and a fluid chamber separated by a 0.2-microns proprietary membrane. Drug transfer is based on electrodiffusion across the membrane. The objective of this study was to determine the feasibility of using this device to achieve adequate serum concentrations of gentamicin in adult healthy volunteers. Ten subjects (age 20-40 years) received a single dose of gentamicin, 1.7 mg/kg through the device. Multiple blood samples were collected and gentamicin was measured by EMIT. Peak serum concentrations of gentamicin ranged from 4.8 to 10.5 micrograms/ml. The mean total clearance, apparent distribution volume and elimination half-life were 0.96 ml/min/kg, 0.16 l/kg and 1.9 h, respectively. No adverse events occurred. These data suggest that a simple membrane device can be used for gentamicin delivery using gravity flow. The device should be evaluated in patients to define its role in therapy. PMID- 2307028 TI - Adolescent abuse forums: improving services for maltreated adolescents. PMID- 2307029 TI - Specialized foster care: treating seriously emotionally disturbed children. PMID- 2307030 TI - Early intervention keeps medically fragile babies at home. PMID- 2307031 TI - Vulnerability in research: a developmental perspective on research risk. AB - Assessing potential risks to children who participate in developmental research is a challenging task because children are a heterogeneous population, varying in developmental competencies and in background characteristics. This essay offers a developmental perspective on research risk, emphasizing that children's vulnerability to research risk changes in complex ways: some risks decrease with increasing age, some increase as the child matures, others change in a curvilinear fashion, while some remain essentially stable with development. Because vulnerability in research does not simply decline linearly with age, assessments of research risk must entail multidimensional considerations that vary over developmental time. In a similar manner, individual characteristics of children at any age (e.g., maltreatment, at-risk status, etc.) may also heighten their vulnerability to certain risks which require special consideration by researchers. Finally, this discussion of developmental vulnerability and the principles underlying research ethics suggests that in addition to the conventional risk/benefit analysis, researchers are in an optimal position to establish and maintain standards of decent treatment of children in research that safeguard their rights as research participants. Suggestions for fostering this process in the research community are outlined. PMID- 2307032 TI - Patterns of compliance from eighteen to thirty months of age. AB - 31 children at 18 months, 32 children at 24 months, and 36 children at 30 months of age were observed in 2 separate 2-hour laboratory sessions with their mother and father to study behavioral responses to demands for compliance. Patterns of compliance to parental commands and requests were examined in 5 laboratory situations. The data revealed no differences in compliance depending upon which parent was present or across the 2-week time interval between the 2 visits, although there was considerable variability in behavior across the 5 situations. Developmental analyses revealed few linear progressions with age, with 24 months signaling an important transition characterized by behavioral reorganization. Taken together, the results encourage reexamining traditional assumptions regarding the development of compliance since it may be most adaptive for children to be responsive to environmental demands and interpersonal constraints. PMID- 2307033 TI - Maternal regulation of children's problem-solving behavior and its impact on children's performance. AB - This study focused on a social interaction theory of the development of cognitive self-regulation. Specifically, the effect of mother-child interaction on the child's ability to problem solve was investigated. The general predictions were (1) children who interacted with their mothers throughout a problem-solving task would subsequently exhibit improved independent performance over practice-control children, who received corrective feedback from a female experimenter at the end of the task; (2) mothers would be more responsible for task activities, would more often regulate their child's task behaviors, and offer more specific verbal content when task demands on child competence increased than when they decreased. 60 3- and 5-year-olds either worked with their mothers or practiced alone and were given corrective feedback on a sorting task in which miniature pieces of furniture were placed in a doll house. As predicted, children who interacted with their mothers subsequently created more correct, adult-like groupings independently than children who received corrective feedback. Mothers displayed more task responsibility and regulation with younger children and when task demands on children of both age groups increased. Maternal verbal content became less specific when task demands decreased. Child performance was related to (1) variation in maternal regulation of the child; and (2) degree of specificity of maternal verbal content. PMID- 2307034 TI - Children's expectations of the outcomes of social strategies; relations with sociometric status and maternal disciplinary styles. AB - To explore relations between maternal disciplinary styles, children's expectations of the outcomes of social strategies, and children's peer status, 144 mothers and their first- (N = 59) and fourth- (N = 85) grade children (ages = 70-86 months and 116-129 months, respectively) participated in home interviews prior to the beginning of the school year. Measures of children's sociometric status were obtained in classrooms after the school year began. Results indicated that children of mothers who were more power assertive in their disciplinary styles tended to be less accepted by peers and tended to expect successful outcomes for unfriendly-assertive methods for resolving peer conflict (e.g., threatening to hit another child). In addition, children who expected unfriendly assertive strategies to lead to self-oriented gains were less accepted by peers. Moreover, maternal disciplinary styles and outcome expectations for unfriendly assertive strategies were found to make separate and independent contribution to peer status. PMID- 2307035 TI - Child-mother attachment of six-year-olds and social competence at school. AB - 89 children and their mothers participated in a study examining the association between attachment and peer social competence. During the summer following kindergarten, quality of attachment was assessed from reunion episodes following a 1-hour separation. In the fall, measures of sociometric status, peer behavior nominations, and peer liking ratings were collected. Teachers completed liking ratings and ratings of behavior problems and competence. Consistent with longitudinal studies of infant attachment and peer relations, insecurely attached boys were less well liked by peers and teachers, were perceived as more aggressive by classmates, and were rated by teachers as less competent and as having more behavior problems than were their secure counterparts. No such associations emerged for girls. Possible explanations for unanticipated differences in the pattern of results for boys and girls are discussed. PMID- 2307036 TI - Change in family work status: effects on parent-adolescent decision making. AB - The interactions of parental work status, family integration, and sex of child on parent-adolescent decision making were examined in a 4-wave study of 504 adolescents and their mothers. 3 work status groups were compared. Deprived families reported a layoff or demotion at Time 1 and no recovery by Time 4. Recovery families reported similar work status losses at Time 1 and reemployment by Time 4. Nondeprived families reported stable employment at both times. Adolescents in deprived households, especially boys, reported the highest conflict with parents. Adolescents in recovery families reported high conflict when parents were unemployed, but levels declined when parents were reemployed. According to mothers, daughters in deprived households enjoyed the highest level of autonomy of any adolescent group. PMID- 2307038 TI - The effects of training in social perspective taking on socially maladjusted girls. AB - A paucity of research exists concerning training programs for the development of interpersonal functioning in socially maladjusted or delinquent adolescent females. Females in a residential institution participated in a role-play program designed to enhance social perspective-taking ability. In 15 sessions girls were coached in specific social skills and acted multiple role perspectives in typical problem situations. Compared to girls in a fitness training program, girls in the role-play training program showed enhanced performance on a measure of social perspective taking. Generalized effects were also found for performance on tests of interpersonal problem analysis, empathy, and the acceptance of individual differences. Additionally, observational data indicated that role-play training resulted in increased prosocial behaviors. Role-play training had no effect on a measure of referential communication. PMID- 2307037 TI - American conceptions of infant development from 1955 to 1984: what the experts are telling parents. AB - The efforts of the child development movement to understand development and the factors influencing it have been the basis of 2 interrelated tasks: the scientific study of children, and the dissemination of this knowledge to parents. Content analysis is used to assess the extent to which psychological theories and research about infants have been communicated to parents from 1955 to 1984 in 2 popular publications, the Infant Care manual and Parents magazine. Results indicated that there is not a singular relation between what experts know and what is communicated to parents. Information reflecting scientific advances about the biological components of infant development (perception, cognition, and temperament) have been most accurately communicated to parents, whereas discussions of the mother-infant relationship, child care, feeding, and fathers appeared to be related to the broader cultural context and demographic changes over the past thirty years. This study reveals an interaction between science and culture in our theories of infant development and child rearing. PMID- 2307039 TI - Development differences in decoding the meanings of the appraisal actions of teachers. AB - Teachers convey evaluations through such "appraisal actions" as ability versus effort attributions for children's performance, spontaneous displays of warmth versus matter-of-fact acceptance, and attention versus inattention. Some appraisal actions (e.g., ability-effort) require an understanding of multiplicative relations to arrive at an "adult" interpretation. Others (e.g., attention-inattention) do not. First through sixth graders watched videotaped scenes in which teachers attributed one child's performance to ability but chided another for lack of effort even though he had given an equivalent performance, hugged one child but not another for equivalent performance, and paid attention to one child's oral report but not another's. Younger students (ages 5-9 to 7-10) rated the ability-attributed and hugged children as smarter; older students (ages 9-9 to 11-10) rated the effort-attributed and unhugged children as smarter. In contrast, no age differences were found in decoding attention versus inattention. The results suggest that younger children use a different strategy in decoding the meanings of complex appraisal actions. PMID- 2307040 TI - The effects of mastery and competitive conditions on self-assessment at different ages. AB - It was hypothesized that self-evaluative accuracy will increase with age in a competitive condition, while even young children will appraise their performance quite accurately in a mastery condition. Children at ages 5, 7, and 10 working in either a match-the-standard or a competitive condition copied a drawing and then evaluated their copies. As hypothesized, competing 5-year-olds overestimated the quality of their copies, and self-assessments became less positive and better correlated with adult judgments with age. There were no age differences in self evaluative accuracy in the mastery condition. Examination of children's explanations for their ratings and their interest in the task supported the interpretation that young children are guided by a nonnormative concept of ability, which can lead to overoptimistic perceptions of competence under competition. Older children tended to adopt normative goals and criteria for self assessment in competition and mastery ones in the match the standard condition, and were realistic about their performance in both. PMID- 2307041 TI - Lies and truth: a study of the development of the concept. AB - This study examined the developmental questions of when children begin to use the terms lie and truth, how they understand them, and when their understanding approaches that of adults. 150 subjects in 5 groups (nursery schoolers, preschoolers, first graders, fifth graders, and adults) were presented a series of 8 short puppet plays that systematically varied the presence of absence of the 3 prototype elements: factuality of a statement, the speaker's belief in the factuality or falsity of the statement, and the speaker's intent to deceive the listeners. The interactions of age, factuality, and belief most fully accounted for the use of the terms lie and truth. Persons at different ages differentially weighed the prototypic elements. Responses of fifth graders were transitional between those of the younger children and adults. The results are interpreted as supporting the development of definitional prototypes for these moral concepts. PMID- 2307042 TI - Affective bias in children's perceptions of dominance relationships. AB - This study investigated children's perceptions of the relative strength of themselves and their peers, in 2 classes of 8-year-olds and 2 classes of 11-year olds. Each child ranked his or her entire class in terms of strength and liking. Previous investigators have assumed that such strength perceptions reflect the dominance structure of the group. The present results, replicating previous findings, indicate that children consistently overestimate their place in this hierarchy in relation to their peers' perceptions. In addition, it was found that bias in perceptions of strength extended in a systematic way to the peer group, with liked peers being overranked and disliked peers being underranked. For most children, this result could be explained in terms of an enhanced evaluation of liked, but not disliked, peers, or in terms of liked, but not disliked, peers being perceived as similar to themselves. The theoretical and methodological implications of these results for the concept of dominance in children's groups are discussed. PMID- 2307043 TI - Concept availability in the causal inferences of children and adults. AB - What supplies the concepts in causal inferences in story comprehension? This question was examined in 5 experiments. Elementary school children and college students listened to stories containing a "premise" sentence describing a character's intent in initiating a series of actions, followed by an unexpected "outcome." After each story, the subjects were asked inference questions about the reason for the outcome (Experiments 1-4) or asked to explain the outcome (Experiment 5). In the various experiments, the availability of object concepts for an inference was manipulated by providing 0 or 2 clues preceding the outcome, additional filler information that diluted the clue information, a mention of an object in the premise or no mention, and an object title for each story or no title. The results suggested that the availability of an object concept in sentences prior to the outcome was a critical determinant of whether an object inference occurred, especially for children. Given availability, the thematic prominence of the object influences whether the object will be used in an inference. PMID- 2307044 TI - The development of text evaluation and revision skills. AB - Children in elementary school settings generally do not revise frequently or skillfully, but relatively little is known about the source of their difficulty with revision. 3 studies were conducted to investigate children's developing ability to evaluate and revise problematic texts. In the first 2 studies, fourth grade (10 years) and sixth-grade (12 years) students were asked to evaluate 3 types of problematic texts and suggest changes to make the texts easier to understand. In the third study, children were asked whether 4 types of revisions improved the comprehensibility of problematic stories. The results showed, first, that older children detected more of the text problems; second, that when younger children spontaneously detected a text problem they were as likely as older children to revise the text adequately; third, that younger children were less able than older children to revise text problems that they had originally overlooked; and, fourth, that younger children overestimated the informativeness of several types of revisions. The results suggest that developmental differences in constructive processing contribute to children's ability to detect and revise text problems. PMID- 2307045 TI - Long-term effects of food supplementation and psychosocial intervention on the physical growth of Colombian infants at risk of malnutrition. AB - 280 Colombian infants at risk of malnutrition were randomly assigned to 1 of 4 experimental groups formed by the presence/absence of 2 interventions: (1) food supplementation for the entire family, from mid-pregnancy until the target child was 3 years old, and (2) a twice-weekly home-visiting program to promote cognitive development, from birth until age 3. All families received free medical care and were studied prospectively. At 3 years of age, children who had received food supplementation averaged 2.6 cm and 642 grams larger than controls. Home visiting and supplementation together reduced the number of children with severe growth retardation. 3 years after intervention (age 6), supplementation effects remained. Children in the home visit condition had become larger than controls, by 1.7 cm and 448 grams. The interactive effect to reduce stunting was marginally significant at this age, and the overall distribution of scores was improved. Other results suggest that changes in family functioning as well as biological mechanisms account for the observed pattern of results. PMID- 2307046 TI - Cortisol release in infants in response to inoculation. AB - Using a cross-sectional design, salivary cortisol was obtained from infants aged 2, 4, and 6 months, prior to and 15 min following an inoculation. Cortisol rose significantly following inoculation. Behavioral responses to inoculation were consistent with the observed patterns of cortisol release. Cortisol base level was significantly and negatively related to the cortisol change score. At 6 months the basal levels also were influenced by an adult-like circadian rhythm; infants tested shortly after awakening had higher basal levels than those tested later in the day. These data provide strong evidence that studies of stress and cortisol release in infants must be sensitive to basal level, circadian rhythm, and behavioral effects, and that appropriate statistical procedures should be employed. PMID- 2307047 TI - Long-term stability of individual differences in sustained attention in the early years. AB - The goal of this longitudinal study was to explore whether early measures of attention and inattention would be predictive of later attentiveness and whether there was any evidence of stable individual differences in attentiveness. Both full-term and preterm children were observed at 1, 2, and 3.5 years in free play and in more structured situations. For the group as a whole, and for full-terms separately, quantitative measures of inattention at 2 years were predictive of comparable measures at 3.5 years. For preterms separately, quantitative measures of inattention at 1 year were predictive of both behavior and the mothers' rating on the Conners Hyperactivity subscale at 3.5 years. Global, qualitative ratings of attentiveness at 1 and 2 years were predictive of mothers' ratings on the Conners at 3.5 years for the group as a whole and for full-terms separately. For full-terms only, the global ratings of attentiveness at 1 and 2 years were also predictive of 3.5-year quantitative measures of behavior. These data provide an encouraging base for further investigation of early individual differences in attentiveness and of possible early precursors of later attention deficits. PMID- 2307048 TI - Infants at social risk: maternal depression and family support services as mediators of infant development and security of attachment. AB - 31 infants at high social risk due to the combined effects of poverty, maternal depression, and caretaking inadequacy were assigned to weekly home-visiting services. At 18 months infant age, the home-visited infants were compared with 2 groups of socioeconomically similar unserved infants on measures of infant development, infant attachment, mother-infant interaction, maternal depression, and maternal social contacts. Home-visited infants of depressed mothers outperformed unserved infants of depressed mothers by an average of 10 points on the Bayley Mental Scale and were twice as likely to be classified as securely attached, with unserved high-risk infants showing a high rate of insecure disorganized attachments. Duration of services was positively correlated with maternal involvement at 12 months. Results of the study point both to the negative developmental consequences associated with severe social risk conditions and to the buffering effects of developmentally oriented home-visiting services for infants at greatest social risk. PMID- 2307049 TI - Effects of maternal behavior on toddler behavior during separation. AB - The influence of maternal preseparation behavior on children's separation behavior was investigated. 72 (36 female, 36 male) 15-18-month-olds met with same gender age-mates for an 8-min play and 4-min separation session. During the play period, mothers were instructed to interact extensively or minimally with their children, or were given no instructions except to interact normally. The noninstructed group was later divided into an extensive and a minimal group. During the separation period, the effect of previous amount of maternal interaction varied according to mothers' instructions and the gender of the children. Children with mothers who were instructed to interact minimally displayed distress sooner and played less with their age-mates than children with noninstructed minimally interacting mothers. Males with minimally interacting mothers spent more time unoccupied and less time playing alone than did females. The findings demonstrate the varying influence that different instructions to mothers may have on children's separation behavior. PMID- 2307050 TI - Direct nonradioactive in situ hybridization of somatic cell hybrid DNA to human lymphocyte chromosomes. AB - Biotinylated DNA from various human-rodent hybrids was hybridized to human lymphocyte spreads after preannealing of the repeated sequences with sonicated total human DNA. Fluorescent labeling was achieved by successive treatments with fluorescein-labeled avidin and biotinylated antiavidin antibody. The use of labeled total DNA from hybrids with known chromosome composition permits the fluorescent staining-("painting") of specific chromosomes, or parts thereof, in human lymphocyte metaphases. Alternatively, the human chromosome content of cell hybrids with unknown chromosome composition is directly assessed from the labeling pattern of human lymphocyte spreads using the total hybrid DNA as probe. PMID- 2307051 TI - Rapid metaphase and interphase detection of radiation-induced chromosome aberrations in human lymphocytes by chromosomal suppression in situ hybridization. AB - Chromosomal in situ suppression (CISS)-hybridization of biotinylated phage DNA library inserts from sorted human chromosomes was used to decorate chromosomes 1 and 7 specifically from pter to qter and to detect structural aberrations of these chromosomes in irradiated human peripheral lymphocytes. In addition, probe pUC1.77 was used to mark the 1q12 subregion in normal and aberrant chromosomes 1. Low LET radiation (60Co-gamma-rays; 1.17 and 1.33 MeV) of lymphocyte cultures was performed with various doses (D = 0, 2, 4, 8 Gy) 5 h after stimulation with phytohaemagglutinin. Irradiated cells were cultivated for an additional 67 h before Colcemid arrested metaphase spreads were obtained. Aberrations of the specifically stained chromosomes, such as deletions, dicentrics, and rings, were readily scored after in situ hybridization with either the 1q12 specific probe or DNA-library inserts. By the latter approach, translocations of the specifically stained chromosomes could also be reliably assessed. A linear increase of the percentage of specifically stained aberrant chromosomes was observed when plotted as a function of the square of the dose D. A particular advantage of this new approach is provided by the possibility to delineate numerical and structural chromosome aberrations directly in interphase nuclei. These results indicate that cytogenetic monitoring of ionizing radiation may be considerably facilitated by CISS-hybridization. PMID- 2307052 TI - Localization of a mouse centromeric DNA repeat in interphase nuclei. AB - The position of a mouse DNA repeat located near the centromere of mouse chromosomes X, 11, 13, and 17 was examined in interphase nuclei of bone marrow and fibroblast cells by in situ hybridization of 3H- or biotin-labeled DNA probe 70-38. In most laboratory mouse strains this probe recognizes a single repeat cluster (DXWas70) close to the centromere of the mouse X chromosome. In a few mouse strains, a second locus (D11Was70, D13Was70, or D17Was70, depending on the mouse strain) is located near the centromere of an autosome. In interphase nuclei from mouse strains with the X-linked locus only, two distinct sites of hybridization were found in female mice and one in male mice. These two sites remained separated during the different phases of the cell cycle (G1, early S, late S, and G2) as demonstrated by in situ hybridization of the probe to flow sorted nuclei. In interphase nuclei from mouse strains with both the X-linked locus and an autosomal locus, four distinct sites of hybridization were found in female mice and three in male mice. Further analysis of loci DXWas70 and D17Was70 showed that these loci were often located in the outer region of nuclei from bone marrow and fibroblast cells. PMID- 2307053 TI - Multiple fluorescence in situ hybridization. AB - A method for multiple fluorescence in situ hybridization is described allowing the simultaneous detection of more than three target sequences with only three fluorescent dyes (FITC, TRITC, AMCA), respectively emitting in the green, red, and blue. This procedure is based on the labeling of (DNA) probes with more than one hapten and visualisation in multiple colors. The possibility to detect multiple targets simultaneously is important for prenatal diagnosis and the detection of numerical and/or structural chromosome aberrations in tumor diagnosis. It may form the basis for an in situ hybridization based chromosome banding technique. PMID- 2307054 TI - Flow cytometric detection of beta-globin mRNA in murine haemopoietic tissues using fluorescent in situ hybridization. AB - The novel method for flow cytometric detection of cellular RNA species in suspended cells by fluorescent in situ hybridization (FC-FISH) was applied in the evaluation of beta-globin expression in murine haemopoietic tissues. Normal murine bone marrow cells and regenerating bone marrow cells obtained after lethal irradiation and bone marrow transplantation as well as murine 15 d fetal liver were examined. Furthermore, spleens and bone marrow of phenylhydrazine-induced anaemic mice were studied. Biotinylated sense- and antisense single strand RNA probes, obtained by transcription of a 510 nucleotides murine beta-globin cDNA sequence subcloned into the pGEM1 plasmid were used as hybridization probes. For detection of the hybrids formed, avidin-FITC was used. Only the antisense beta globin probe gave strongly positive fluorescence signals in a defined population of cells in each of the tissues examined, whereas the sense probe did not give signals higher than control samples. Melting characteristics of the hybrids showed the specificity of the in situ hybridization reaction. Forward light scatter distributions, reflecting cell size of the positive cells were as expected from erythroid cells. Within the erythrocyte subpopulation both beta globin-negative and -positive cells were detected. The percentages of positive cells determined flow cytometrically correlated with the percentages observed in May-Grunwald/Giemsa stained preparations. Differences observed in fluorescence intensity between positive cells of different organs were no larger than about a factor of two, indicating a rather constant beta-globin mRNA content over the entire differentiation range. An exception was 15 d fetal liver, which was shown biochemically to contain about eight times more beta-globin RNA and which had a 2.4 times higher fluorescence intensity. We estimate that the sensitivity of the present method is such that as little as 500 copies per cell of a specific mRNA of 1 kb length would be detectable. PMID- 2307055 TI - High resolution mapping of Xenopus laevis 5S and ribosomal RNA genes by EM in situ hybridization. AB - We have developed a modification of in situ hybridization at the electron microscope level that permits simultaneous detection of at least two sequences. Probes are labelled with either biotin or AAF and detected with two distinct sizes of colloidal gold. This protocol has been applied to map the positions of Xenopus laevis oocyte-type 5S genes relative to ribosomal precursor genes in several independently derived cell lines. The results for the line TRXO, which expresses some oocyte 5S RNA, indicate that this inappropriate expression is not due to translocation from telomeric sites into the nucleolus organizer, as previously hypothesized. In addition we found that four other Xenopus cell lines, none of which express these genes, also contain distinct 5S oocyte translocations. These results suggest that an alteration in chromosome position is insufficient to result in gene activation and that sequences which are telomeric-proximal are exceptionally prone to translocation. PMID- 2307056 TI - Flow cytometric quantification of human chromosome specific repetitive DNA sequences by single and bicolor fluorescent in situ hybridization to lymphocyte interphase nuclei. AB - Fluorescent in situ hybridization allows for rapid and precise detection of specific nucleic acid sequences in interphase and metaphase cells. We applied fluorescent in situ hybridization to human lymphocyte interphase nuclei in suspension to determine differences in amounts of chromosome specific target sequences amongst individuals by dual beam flow cytometry. Biotinylated chromosome 1 and Y specific repetitive satellite DNA probes were used to measure chromosome 1 and Y polymorphism amongst eight healthy volunteers. The Y probe fluorescence was found to vary considerably in male volunteers (mean fluorescence 169, S.D. 35.6). It was also detectable in female volunteers (mean fluorescence 81, S.D. 10.7), because 5-10% of this repetitive sequence is located on autosomes. The Y probe fluorescence in males was correlated with the position of the Y chromosome cluster in bivariate flow karyotypes. When chromosome 1 polymorphism was studied, one person out of the group of eight appeared to be highly polymorphic, with a probe fluorescence 26% below the average. By means of fluorescent in situ hybridization on a glass slide and bivariate flow karyotyping, this 26% difference was found to be caused by a reduction of the centromere associated satellite DNA on one of the homologues of chromosome 1. The simultaneous hybridization to human lymphocyte interphase nuclei of biotinylated chromosome 1 specific repetitive DNA plus AAF-modified chromosome Y specific DNA was detected by triple beam flow cytometry. The bicolor double hybridized nuclei could be easily distinguished from the controls. When the sensitivity of this bicolor hybridization is improved, this approach could be useful for automatic detection of numerical chromosome aberrations, using one of the two probes as an internal control. PMID- 2307057 TI - System for flow sorting chromosomes on the basis of pulse shape. AB - Sorting on the basis of the complex features resolved by chromosome slit-scan analysis requires rapid and flexible pulse shape acquisition and processing for determining sort decisions before droplet breakoff. Fluorescence scans of chromosome morphology contain centromeric index and banding information suitable for chromosome classification, but these scans are often characterized by variability in length and height and require sophisticated data processing procedures for identification. Setting sort criteria on such complex morphological data requires digitization and subsequent computation by an algorithm tolerant of variations in overall pulse shape. We demonstrate here the capability to sort individual chromosomes based on their morphological features measured by slit-scan flow cytometry. To do this we have constructed a sort controller capable of acquiring an 128 byte chromosome waveform and executing a series of numerical computations resulting in an area-based centromeric index sort decision in less than 2 ms. The system is configured in a NOVIX microprocessor, programmed in FORTH, and interfaced to a slit-scan flow cytometer data acquisition system. An advantage of this configuration is direct control over the machine state during program execution for minimal processing time. Examples of flow sorted chromosomes are shown with their corresponding fluorescence pulse shapes. PMID- 2307058 TI - Clinical applications of flow karyotyping in myelocytic leukemia by stimulation of different subpopulations of cells in blood or bone marrow samples. AB - Examples are presented in which normal as well as abnormal chromosome distributions could be obtained from the same individual by means of bivariate flow karyotyping. Selective stimulation of T-lymphocytes obtained by E-rosetting from the blood of a patient with acute myelocytic leukemia resulted in a normal flow karyogram. The specific stimulation of myelocytic leukemia cells with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL 3) yielded flow karyograms displaying the leukemia-associated chromosome abnormalities. The resulting flow karyograms could be used to discriminate between homolog differences, which appear normally in virtually every individual, and leukemia-associated chromosomal aberrations. In the case of a female chronic myelocytic leukemia patient who received bone marrow form an HLA-identical male donor, specific stimulation of various subsets of cells enabled to discriminate between leukemic host cells and non-leukemic donor cells. Both the leukemia specific translocations and sex chromosomes were used as markers to analyse the flow karyograms obtained from the same sample. PMID- 2307059 TI - Construction of gene libraries for each human chromosome. AB - We describe the construction of two complete sets of small insert, complete digest DNA libraries for each of the 24 human chromosomal types by the National Laboratory Gene Library Project. Flow sorting was used to purify the chromosomes which provided the DNA for cloning. One set of libraries was cloned into the HindIII site of the lambda vector Charon 21A, and the other set was cloned into the EcoRI site of the same vector. Characterization information from both in house experiments and user feedback is presented. These chromosome-specific libraries are available to the general scientific community from a repository at the American Type Culture Collection, Rockville, MD. The second phase of the project, the construction of large insert, partial digest libraries in both lambda and cosmid vectors, is underway. PMID- 2307060 TI - Automatically inferred Markov network models for classification of chromosomal band pattern structures. AB - A structural pattern recognition approach to the analysis and classification of metaphase chromosome band patterns is presented. An operational method of representing band pattern profiles as sharp edged idealized profiles is outlined. These profiles are nonlinearly scaled to a few, but fixed number of "density" levels. Previous experience has shown that profiles of six levels are appropriate and that the differences between successive bands in these profiles are suitable for classification. String representations, which focuses on the sequences of transitions between local band pattern levels, are derived from such "difference profiles." A method of syntactic analysis of the band transition sequences by dynamic programming for optimal (maximal probability) string-to-network alignments is described. It develops automatic data-driven inference of band pattern models (Markov networks) per class, and uses these models for classification. The method does not use centromere information, but assumes the p q-orientation of the band pattern profiles to be known a priori. It is experimentally established that the method can build Markov network models, which, when used for classification, show a recognition rate of about 92% on test data. The experiments used 200 samples (chromosome profiles) for each of the 22 autosome chromosome types and are designed to also investigate various classifier design problems. It is found that the use of a priori knowledge of Denver Group assignment only improved classification by 1 or 2%. A scheme for typewise normalization of the class relationship measures prove useful, partly through improvements on average results and partly through a more evenly distributed error pattern. The choice of reference of the p-q-orientation of the band patterns is found to be unimportant, and results of timing of the execution time of the analysis show that recent and efficient implementations can process one cell in less than 1 min on current standard hardware. A measure of divergence between data sets and Markov network models is shown to provide usable estimates of experimental classification performance. PMID- 2307061 TI - Stylized chromosome images. AB - Stylized chromosome images 1) serve as a format to test effects of preprocessing algorithms used in automated karyotyping; 2) enhance the ability of humans to perform quantitative analysis of chromosomal aberrations; 3) provide an alternative format for karyotype hard copies produced by automated systems. Stylized chromosomes are two-dimensional computer-generated images based on information extracted from one-dimensional width and density profiles. These profiles correspond to what cytogeneticists observe through the microscope as the shape and banding patterns of stained chromosomes. Stylized presentation sharpens chromosome band boundaries and perimeters, reduces "noise," and enhances gray level variations, which are difficult to distinguish by humans on photographic or computer generated karyotypes. Karyotyping accuracy using stylized images was used to detect difficult areas for automated chromosome identification. Landmark bands sufficient to classify chromosomes were identified; shapes of chromosomes reflected in width profiles were said to aid classification. A two-step automated karyotyping strategy proposed is: 1) classify chromosomes by landmarks, minimum information needed for identification; 2) subsequently employ the full banding pattern with maximum resolution to detect aberrations. Stylized images of abnormal chromosomes have potential for testing hypothesis regarding breakpoints and quantitative analysis, but improvements are needed in homologue normalization and definition of termini of chromosomes. PMID- 2307062 TI - The Athena semi-automated karyotyping system. AB - In this article we describe Athena, a system that provides for semi-automated karyotyping of metaphase spreads. The system is based upon the Macintosh II computer. It uses software that is written entirely in C and consists of approximately 200 Kbytes of executable code. Athena provides automated segmentation of metaphase images into individual chromosomes, automated measurements on each banded chromosome, and automated classification into the standard Paris-convention karyotype. Furthermore, the system provides the ability to construct one or more chromosome data bases to represent the types of metaphase spreads and staining techniques that may be used in a given laboratory. Because we believe that it is impossible to construct a system that can achieve perfect segmentation, perfect separation of touching and overlapping chromosomes, perfect localization of the centromeres, and perfect classification, the system offers the possibility for interaction at each of the above stages using the well accepted Macintosh user interface. PMID- 2307063 TI - Experience with the Athena semi-automated karyotyping system. AB - The traditional analysis and assembly of metaphase chromosomes into a karyogram is a slow and tedious process requiring intermediate photographic steps and manual manipulation of the chromosome images. Much of this task is highly repetitive and readily lends itself to partial automation. Semi-automated karyotyping systems now are being used increasingly in both clinical and research cytogenetic laboratories. Digital image processing techniques are used to capture, manipulate, and make an initial classification of chromosome images. The Athena system uses commercially available components based on a Macintosh II personal computer. Digital image processing procedures automatically isolate chromosome images from the metaphase and arrange them into a karyogram, using information about relative chromosome length, centromeric index, and banding pattern. The operator uses the intuitive graphics interface of the Macintosh computer to monitor each phase of the analysis, to resolve any problems in isolating chromosome images, and to rearrange the individual chromosome images while assembling the final karyogram. Athena is designed as a semi-automated karyotyping system that is easy to learn and has sufficient power and versatility for routine use in the analysis of human metaphase chromosomes. PMID- 2307064 TI - Automatic detection of fragile X chromosomes using an X centromere probe. AB - In order to score for the fragile X syndrome, blood samples are prepared with absorption stain labeling by in situ hybridisation of the X chromosome centromeres. Metaphases are located, digitised at high resolution, and segmented fully automatically. A three stage adaptive classification scheme for labeled X chromosomes is then applied. This consists of a simple box classifier to identify plausible X and false positive X chromosomes, followed by a quadratic discriminant classifier that is re-trained for each sample. The modal number of X chromosomes is then determined for each sample and used to refine the classification. A simple fragile site detector is applied to the distal portion of the detected X chromosome long arms. From the results we estimate computer and operator time requirements for a screening system in which the operator reviews only the apparently fragile X chromosomes detected by the computer. PMID- 2307065 TI - A unified model of eukaryotic chromosomes. AB - A revised model of DNA packaging into chromosomes is presented. Its features are consistent with observed structural dimensions and the molecular periodicities related to transcription, replication and matrix attachment domains. The transitions between euchromatic, heterochromatic and metaphase states are explained simply. Molecular and physical properties of chromosomal bands, and their correlation with specific DNA sequence motifs are discussed. PMID- 2307066 TI - Discrepancies between flow cytometric and cytogenetic studies in the detection of aneuploidy in human solid tumors. AB - Parallel flow cytometric (FCM) cell DNA studies and cytogenetic studies were performed on clinical samples from twenty human solid tumors of various types and on cell lines established in tissue culture from three of these tumors. Six of twenty clinical samples (30%) showed concordance between flow cytometry and cytogenetics with respect to the presence or absence of aneuploidy. Among the fourteen cases with discrepancies between the two methods, 8 (40% of all cases) showed hypodiploidy by cytogenetics and had diploid DNA histograms. Three cases (15%) had prominent discrete peaks in the triploid to tetraploid region by cytogenetics but had only barely discernible corresponding peaks in the DNA histogram. In two cases (10%) cytogenetic studies revealed diffuse aneuploidy. Cytogenetic studies demonstrated near-tetraploidy in three samples, but only one of these was detected by FCM; all three cases exhibited other numerical chromosomal abnormalities. In one case aneuploidy was demonstrated by FCM and not by cytogenetics. Among the tumor cell lines established in culture, the DNA Index was often higher than the cytogenetic index. Overall, 13/20 or 65% of patients with solid tumors in this study had numerical chromosomal abnormalities that were not detected by flow cytometry. Eleven of these patients had distant metastases at the time of tumor sampling, and nine of these died of their disease within 1 11 months of the time of study. PMID- 2307067 TI - Coprophilous mite communities as affected by concentration of plastic and glass particles. AB - The community and trophic structure of mites was examined in cattle manure and their response to treatment of manure with solid-waste particles was investigated. Mites were collected from artificial dung pats exposed to natural colonization in the field for 16 days. The pats were composed of manure alone or manure separately mixed with waste-material particles of four types and concentrations. Mites were the numerically dominant taxon among arthropods in manure. The Prostigmata was the most abundant suborder, mainly represented by the families Pygmephoridae and Ereynetidae. The common families of Mesostigmata were all cosmopolitan. Correlations with other arthropods suggest that Mesostigmata are opportunistic predators, preying upon dipteran larvae, Collembola and other mites, and preyed upon by larger predatory insect larvae. Cryptostigmata and Astigmata were a numerically minor community component. The species composition and abundance upon treatment of manure with polyethylene, polystyrene and glass particles was similar to that of the treatment control, i.e. natural and inert sand. Relatively low concentrations, 5 and 30% (v/v), of particles in manure did not alter the mite communities despite important differences with untreated manure in final moisture content. These findings may be relevant to proposed methods of solid-waste disposal. High particle concentrations of 60 and 90% had detrimental effects to the abundance of mites in manure and were caused by the very low final moisture content and probably nutrient deficiency of these treatments. The persistence of members of the prostigmatid families Tydeidae, Nanorchestidae and Tarsonemidae in the moisture-deficient 90%-concentration treatments supports previous evidence of adaptations to low-water-content habitats. PMID- 2307068 TI - Fine structure of the fat body and nephrocytes in the life-stages of Dermacentor variabilis. AB - The fine structure of the fat body and associated nephrocytes of the American dog tick, Dermacentor variabilis (Say), was described in unfed larvae, unfed nymphs, and in unfed and fed adults of both sexes. The fat body consisted of one type of cell, the trophocyte. Morphological changes that occurred in the trophocytes of both sexes were dependent on feeding. The ultrastructure of feeding male trophocytes was distinct from trophocytes of feeding females. In the feeding female, the trophocyte developed an ultrastructure characteristic of cells that produce secretory proteins. A type of scalariform cell junction was found associated with rough endoplasmic reticulum of the trophocytes. Nephrocytes were closely associated with trophocytes but were not part of the fat body. Nephrocyte ultrastructure was unaltered throughout the life-stages we examined, except at the end of oviposition. Organelles in the nephrocytes were not randomly distributed, but were found in distinct regions of the cytoplasm. Slit diaphragms at the surface of the nephrocytes were extracellular specializations that had a periodic ultrastructure. PMID- 2307069 TI - Environmental actions of agrochemicals. 1. Side-effects of the herbicide 3-amino 1,2,4-triazole on a laboratory acarine/host-plant interaction (Tetranychus urticae/Phaseolus vulgaris) as revealed by electron microscopy. AB - Foliar and soil application in concentrations below the recommended rate of the herbicide 3-amino-1,2,4-triazole to the host plant Phaseolus vulgaris L. results in structural alterations of the protein-synthesizing apparatus of midgut and salivary-gland cells of the phytophagous spider mite Tetranychus urticae Koch (Acari: Tetranychidae) independent of its mode of application. With prolonged incubation times cytological defects become more intense, and spread to more cells and tissues. Resultant effects on yolk and egg formation were expressed as an inhibition of egg deposition that led to a decrease in the reproduction rate of T. urticae. Consequences of 3-amino-1,2,4-triazole action on T. urticae are discussed with regard to its value to a host-plant/parasite model, agricultural practices and environmental impacts. PMID- 2307070 TI - Attempted transmission of Ehrlichia risticii, causative agent of Potomac horse fever, by the ticks, Dermacentor variabilis, Rhipicephalus sanguineus, Ixodes scapularis and Amblyomma americanum. AB - Dermacentor variabilis, Rhipicephalus sanguineus, Amblyomma americanum, and Ixodes scapularis ticks were investigated for their ability to transmit Potomac horse fever. Larval and nymphal ticks were exposed to Ehrlichia risticii by feeding on mice inoculated with the organism. Molted exposed ticks were then allowed to feed on susceptible ponies or mice. No evidence of transmission, either clinically or by detection of antibodies to E. risticii in mice or ponies, was observed for any tick species examined. PMID- 2307071 TI - Immunity of the ox to the brown ear tick Rhipicephalus appendiculatus. AB - Controlled repeated infestation of Bos taurus and Bos indicus cattle resulted in a decline in the recovery of all R. appendiculatus instars. Resistance to infestation varied between individuals although all individuals manifested severe hypersensitivity at the attachment site, which was reflected in the grooming reflex. PMID- 2307072 TI - An Australian record of the American dog tick Dermacentor variabilis, and the risk of its establishment outside North America. AB - A living female of Dermacentor variabilis (Say) was collected in Canberra, Australia, on a human who had recently returned from the U.S.A. Climatic data indicate that this could become established in eastern Australia and many other parts of the world, with serious consequences for human and animal health. PMID- 2307073 TI - Differentiation of mite species by using cellulose acetate and equilibrium polyacrylamide gel electrophoresis of isoenzymes. AB - The isoenzymes of various species of medically and economically important mites were studied using cellulose acetate and equilibrium polyacrylamide gel electrophoresis. Interspecific differences in isoenzymes were found, which were species-specific. Intraspecific differences in isoenzymes were also found when individual mites were examined. The efficiency of each technique, and their use in various fields of acarology, are discussed. In addition, possible phylogenetic relationships as revealed by these techniques are suggested. PMID- 2307074 TI - Diagnosis of chest pain of esophageal origin. A guideline of the Patient Care Committee of the American Gastroenterological Association. PMID- 2307075 TI - Comparison of esophageal manometry, provocative testing, and ambulatory monitoring in patients with unexplained chest pain. AB - Prolonged ambulatory esophageal pH and pressure monitors are being developed to evaluate noncardiac chest pain. This new technology needs comparison with conventional esophageal tests before determining which studies are most useful in diagnosing and treating esophageal chest pain. Therefore, we studied 45 patients with esophageal manometry, acid perfusion and edrophonium tests, and 24 hr pH and pressure monitoring. Manometry was abnormal in 20 patients (44%) with nutcracker esophagus, the most common motility disorder. Fifteen (33%) had positive acid perfusion test and 24 (55%) positive edrophonium test. During ambulatory monitoring, all patients experienced chest pain with a total of 202 individual events: 32 events (15%) secondary to acid reflux, 15 (7%) secondary to motility abnormalities, 7 (3%) to both pH and pressure changes, and 149 events (74%) occurred in the absence of any abnormal pH or motility changes. Patients with normal manometry were significantly (P less than 0.01) more likely to have acid reflux chest pain events than did nutcracker patients, who had an equal frequency of pH and motility events. A positive acid perfusion test was significantly associated with abnormal pressure events (P = 0.02; odds ratio 5.95), while a positive edrophonium test more likely predicted acid reflux chest pain during 24 hr monitoring (P = 0.007; odds ratio 7.25). Therefore, abnormal manometry and positive provocative tests point to the esophagus as the likely source of chest pain. However, ambulatory pH and pressure monitoring are required to accurately define the relationship between chest pain and acid reflux or motility disorders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307076 TI - Gastric emptying for solids in patients with duodenal ulcer before and after highly selective vagotomy. AB - In a series of 31 duodenal ulcer patients (23 males and 8 females), who underwent a highly selective vagotomy, gastric emptying characteristics of a solid meal, labeled with [99mTc]stannous colloid, were assessed before, two weeks and six months after operation. The clinical diagnosis was confirmed by endoscopy and x ray; failure of treatment with H2 antagonists or antacids during 1-18 (mean 5) years was the direct indication for operative treatment. A temporary delay in gastric emptying is noted two weeks after operation (T1/2: 124 vs 57 min). After six months, gastric emptying time has practically normalized. It appears that this is the result of the preservation of the antropyloric vagal nerve supply. In these patients, a 10% recurrence rate is noted, comparable to the results in the literature. Highly selective vagotomy proves to be a safe and effective procedure with few side effects. It does not impair gastric motility. PMID- 2307077 TI - Effect of mucosal thickening near gastric carcinoma on the endoscopic diagnosis of malignancy. AB - Gastric mucosal thickening of variable degree occurs in the vicinity of gastric carcinomas and is possibly related to simultaneous tumor expression of epidermal growth factor and its receptor. Seventeen cases in which both endoscopic biopsy and subsequent resection for gastric carcinoma had been performed were studied to see if putative tumor-related mucosal thickening had an effect on endoscopic biopsy sensitivity. Biopsy fragment positivity rate was greater in cases with exophytic, protruding tumor masses (46.8 +/- 8.5%) than in all other cases (17.0 +/- 4.7%; P = 0.02). Thickness of nontumorous mucosa adjacent to carcinomas did not significantly affect the biopsy fragment positivity rate in cases with exophytic masses ("thin" subgroup, 51.0 +/- 16.2%; "thick" subgroup, 44.0 +/- 10.8%; P = 0.7) but did reduce the positivity rate significantly (P = 0.05) in ulcerative or infiltrative tumors without exophytic components ("thin" subgroup, 23.3 +/- 4.1%; "thick" subgroup, 8.4 +/- 2.1%). This reduction in biopsy sensitivity related to mucosal thickening occurring adjacent to nonprotuberant lesions may explain, at least in part, the variable rates of positive biopsies observed with gastric cancers. PMID- 2307078 TI - Prevalence of duodenal ulcer in cirrhotic males referred for liver transplantation. Does the etiology of cirrhosis make a difference? AB - The prevalence of symptomatic duodenal ulcer (DU) assessed primarily in alcoholic males with cirrhosis is estimated to be approximately fivefold increased compared to the normal population. Little information is available, however, as to the prevalence of DU in nonbleeding, nonalcoholic subjects with cirrhosis. In order to estimate the prevalence of DU in males with various types of cirrhosis and its relation to the degree of portal hypertension, 216 male cirrhotic patients (165 with parenchymal liver disease and 51 with cholestatic liver disease) being evaluated for liver transplantation at the University of Pittsburgh between January 1985 and June 1987 underwent pan-upper gastrointestinal endoscopy. The prevalence of DU in each group was 7.8%. However, among the various subgroups it was as follows: chronic active hepatitis due to HBV: 9.4%, alcoholic: 12.2%, cryptogenic: 3.5%, autoimmune chronic active hepatitis: 6.6%, primary sclerosing cholangitis (PSC): 9.5%. The reference data for this study consist of data reported in the literature obtained in 355 healthy asymptomatic male volunteers. The prevalence of DU in this group is significantly less than in the study group (2.2% vs 7.8%; P less than 0.005). While the estimated risk for a DU is increased 3.71-fold (95% CI: 8.74, 1.57; P less than 0.005) in cirrhotic males in general as compared to normal males, only the subgroups with CAH due to HBV, alcoholism, and PSC were found to have an increased estimated risk of DU (all at least P less than 0.01). No association between the prevalence of DU and degree of portal hypertension could be demonstrated in either group. PMID- 2307079 TI - Uptake of L-carnitine by rat jejunal brush border microvillous membrane vesicles. Evidence of passive diffusion. AB - We have previously described apparent active transport of carnitine into rat intestinal mucosa with intracellular accumulation against a concentration gradient in a process dependent upon the presence of sodium ions, oxygen, and energy. In the work described here, we sought to define the interaction between carnitine and the brush border membrane, which we presumed contained the transport mechanism. Using isolated rat jejunal brush border microvillous membrane vesicles, we found evidence of passive diffusion alone. We found no evidence of carrier-mediated transport--in particular no saturation over a concentration range, inhibition by structural analogs, transstimulation phenomenon, and no influence of sodium ions, potential difference or proton gradients. We conclude that a carnitine transporter does not exist in the brush border membrane of enterocytes and that other cellular mechanisms are responsible for the apparent active transport observed. PMID- 2307080 TI - Dysplasia and cancer complicating strictures in ulcerative colitis. AB - Previous studies have found a widely variable prevalence of dysplasia and cancer in colonic strictures in patients with ulcerative colitis. Consequently, therapeutic recommendations are conflicting. To better assess the prevalence, we reviewed the clinical and pathological findings in all 27 patients with ulcerative colitis complicated by stricture who were entered into our Inflammatory Bowel Disease Registry. A true stricture was defined as a persistent localized narrowing of the colon found on air-contrast barium enema or on colonoscopy. Upon careful review, 12 of 27 patients were found to have transient colonic spasm, not a stricture, and were excluded. The remaining 15 patients with true strictures represented 3.2% of all ulcerative colitis patients in the registry. Strictures were identified at 13.3 +/- 9.9 years following the diagnosis of ulcerative colitis. Eleven patients had multiple strictures that were principally located in the left colon. Of the 15 patients, 11 had dysplasia and two had cancer found on colonoscopic biopsy. Ultimately, six patients had carcinoma found at colonoscopy or colectomy (three modified Dukes' stage A, one stage B, and two stage D). All cancers were at the site of a stricture. These findings indicate that a true colonic stricture in ulcerative colitis is frequently associated with dysplasia and cancer, which can be diagnosed with colonoscopic biopsy. A stricture should be considered a strong risk factor for cancer, requiring intensive colonoscopic surveillance. If dysplasia is discovered, or if the stricture cannot be adequately biopsied, consideration should be given to total colectomy. PMID- 2307081 TI - Effect of cholera toxin on small intestinal motor activity in the fed state. AB - We sought to determine the effect of cholera toxin on small intestinal transit and motor activity in the fed state. Mean transit time increased after cholera toxin, but there was no change in mean amplitude, duration, and area of contractions. In contrast, there was a reduction in the total amplitude, duration, and area of contractions, and this was due to a decrease in frequency of contractions. The reduction in the total parameters of all contractions could be accounted for by a reduction in the same parameters for propagating contractions. The parameters of nonpropagating contraction were not different after cholera toxin. Also, there was a decrease in the distance of propagation of contractions. Our findings demonstrate that during the secretory state due to cholera toxin the small intestinal motor activity works in a compensatory mode to decrease transit and allow more time for absorption. PMID- 2307082 TI - New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. AB - We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr. The contents of pancreatic protein, DNA, and digestive enzymes were markedly reduced after the arginine injection and reached their nadirs at 72 hr. After 14 days these levels were almost normal. Histologic examination revealed a number of small vesicles within acinar cells at 6 hr, which were identified as markedly swollen mitochondria by the electron microscope. Other intracellular organelles and nuclei also showed degenerative changes. At 12 hr interstitial edema appeared, and acinar cell necrosis was seen after 24 hr. The extent and severity of necrotic changes of pancreatic exocrine tissue with inflammatory cell infiltration were maximal at 72 hr. At seven days, pancreatic acinar cells began to regenerate, and pancreatic architecture appeared almost normal after 14 days. The present study has demonstrated that the administration of excessive doses of arginine induces a new, noninvasive experimental model of acute necrotizing pancreatitis. PMID- 2307083 TI - Hospital discharges for inflammatory bowel disease. Time trends from England and the United States. AB - The present study analyzes time trends of inflammatory bowel disease (IBD) in England-Wales and the United States based on nationwide hospitalization statistics. Because these statistics cover the total population of each country, they may give a more representative picture of the true trends than previous analyses concerning only one region or health center. The Hospital In-patient Enquiry was used to evaluate time trends in England-Wales from 1962 to 1985, data from the National Hospital Discharge Survey and the Commission on Professional Activities were used for trends in the United States from 1970 to 1987. A rise of Crohn's disease persisted unabated in the old age groups throughout the observation period. It was less marked in those aged under 35 and reached a plateau during the most recent decade. In ulcerative colitis, discharge rates increased in the older age groups, but remained constant or declined in the middle or younger age groups, respectively. Similar trends were observed in all three surveys. The hospitalization data confirm similar age-specific trends of mortality. The difference between younger and older age groups suggests that generations born 60-80 years ago have become more likely to be affected by IBD leading to hospitalization and mortality. As these high-risk generations grow older, there is a relative rise of hospitalization and mortality from IBD in these subjects. PMID- 2307084 TI - Pancreoscopic diagnosis of intraductal cystadenoma of the pancreas. PMID- 2307085 TI - Effect of ranitidine on acetaminophen-induced hepatotoxicity in dogs. AB - The effect of ranitidine administration upon the hepatotoxic effect produced by a multidose acetaminophen administration regimen was examined. Seventy-two dogs received three subcutaneous injections of acetaminophen (750, 200, 200 mg/kg body wt) in DMSO (600 mg/ml) at time zero, 9 hr later, and 24 hr after the first dose. Ten control animals (group I) were not given ranitidine, the remaining 62 dogs received an intramuscular injection of ranitidine 30 min before each acetaminophen dose. Three different doses of ranitidine were used (mg/kg body wt): 50 mg, group II (33 dogs); 75 mg, group III (14 dogs); 120 mg, group IV (15 dogs). Ranitidine reduced the expected acetaminophen-induced hepatoxicity in a dose-response manner. Moreover, a significant correlation was found between the ranitidine dose and the survival rate, as evidenced by transaminase levels in the serum and histology of the liver. This model of fulminant hepatic failure induced by acetaminophen and its modulation with ranitidine provides clinical investigators with a research tool that will be useful in the future investigation of putative medical and surgical therapies being investigated for use in the clinical management of fulminant hepatic failure. Because of the size of the animal used in this model, frequent and serial analyses of blood and liver were available for study to determine the effect of therapy within a given animal as opposed to within groups of animals. PMID- 2307086 TI - Cyclosporine augments hepatic regenerative response in rats. AB - A number of mechanisms participate in the hepatic injury that occurs during and following liver transplantation. A normal allograft regenerative response is probably essential for a successful transplant outcome. In this study, the effect of cyclosporine, a potent immunosuppressant used routinely after liver transplantation, on the regenerative response of the liver after partial hepatectomy was investigated. Male Wistar rats were pretreated for one week with either cyclosporine or the olive oil vehicle and were subjected to either a two thirds partial hepatectomy or a sham operation. Animals were sacrificed at various times postoperatively and the remnant livers were weighed to determine the liver weight to body weight ratio, two biochemical measures of a regenerative response (cytosolic ornithine decarboxylase activity and thymidine kinase activity), and the hepatic content of estrogen and androgen receptors, as the content of these receptors has been shown to modulate, at least in part, the subsequent hepatic regenerative response. The preoperative hepatic cytosol content of ornithine decarboxylase, thymidine kinase, and estrogen receptor was significantly greater (P less than 0.05) in rats pretreated with cyclosporine than in those treated with the vehicle alone. A significant increase in ornithine decarboxylase and thymidine kinase activities occurred after partial hepatectomy in both the cyclosporine-pretreated and vehicle-pretreated animals. The absolute levels for each parameter were also greater in the cyclosporine-treated animals than in the vehicle-treated controls at 24 hr after partial hepatectomy (P less than 0.05). The pattern of change in the hepatic cytosolic content of estrogen and androgen receptors in both groups of animals was comparable with those described previously for regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307087 TI - Relationship between small intestinal fasting motility and vomiting in dogs. AB - Preceding vomiting, several changes in small intestinal motility have been described. They consist mainly of high-amplitude retrograde contractions and inhibition of motility before and after these contractions. The recordings of 94 episodes of emesis occurring spontaneously, during manometric studies of intestinal motility by means of infused catheters in dogs with gastric and duodenal cannulae, showed that 95.7% of all episodes developed during phase II of the migratory motor complex. In order to establish whether different phases of the fasting cyclic activity are associated with a different sensitivity to emetic stimulus, two agents, apomorphine, a centrally acting drug and copper sulfate, a peripherally acting agent, were administered at the beginning of phases I and II of the migratory motor complex. Coincident with spontaneously occurring vomiting, a statistically significative greater number of responses to both emetic agents was observed during phase II as compared to phase I. This finding suggests that cyclic changes of the small bowel motility are related to changes in the threshold of the vomiting center. PMID- 2307088 TI - Noncardiac chest pain, the crumbling of the sphinx. PMID- 2307089 TI - Diabetes mellitus and molecular biology. An international symposium. San Antonio, Texas, 24-27 September 1989. Proceedings. PMID- 2307090 TI - Effect of a new lente insulin on diabetics. AB - Thirty diabetics who had been receiving ordinary insulin were switched to S-lente insulin, a new mixture of four parts semilente and six parts ultralente insulin. Eight times a day, we measured the glucose, insulin, and C-peptide (CPR) in their blood. Those with more than 250 mg/dl postprandial glucose were designated group A (18 patients) and the other were designated group B (12 patients). Group A diabetics experienced a significant decrease in fasting blood glucose levels whereas group B did not. S-lente improved the daily blood glucose profiles of 72% of group A and 25% of group B. It slightly reduced the sum of the daily blood glucose in group A and did not affect those of group B. The M-value fell significantly in group A but not in group B. Changes in this value correlated significantly with those of blood glucose determination sums. The sums of the determinations of free plasma insulin and CPR remained unaffected by the new insulin. It is concluded that S-lente insulin controls the blood glucose of diabetics whose postprandial blood glucose cannot be controlled by ordinary insulin. PMID- 2307091 TI - Relationship between glycemic control and orthostatic hypotension in type 2 diabetes mellitus--a survey by the Fukuoka Diabetes Clinic Group. AB - We examined the prevalence of orthostatic hypotension and its association with glycemic control, as assessed by hemoglobin A1 (HbA1) concentration, in type 2 diabetic patients. The prevalence of orthostatic hypotension in 886 diabetics who were referred to our study and in 587 diabetics who were not given any antihypertensive drugs was 7% and 6%, respectively. The relationship between orthostatic hypotension and HbA1 levels was evaluated only in subjects not receiving antihypertensive drugs, since antihypertensive agents might induce orthostatic hypotension. HbA1 levels were 11.0 +/- 2.1% in the diabetic patients with orthostatic hypotension, which was significantly higher than the HbA1 levels of 9.9 +/- 2.2% in the diabetic patients without orthostatic hypotension. Multivariate analysis also revealed that the association remained significant after adjustment for the treatment and duration of diabetes, age, sex and body mass index. These findings suggest that glycemic control contributes to the development of orthostatic hypotension in type 2 diabetic patients. PMID- 2307092 TI - The prevalence of micro-albuminuria and glomerular hyperfiltration in young patients with IDDM. AB - We have assessed the prevalence of two risk factors for diabetic nephropathy, i.e., micro-albuminuria and a raised glomerular filtration rate (GFR), in 127 insulin-dependent diabetic patients aged 13-36 years. Micro-albuminuria (albumin excretion rate (AER) 20-200 micrograms/min) was found in 46 subjects (36%) and GFR was elevated (greater than 135 ml/min/1.73 m2) in 43 (34%). The prevalence of supranormal GFR declined and that of micro-albuminuria rose progressively with the increasing duration of diabetes. While age and sex distribution were similar in subjects with and without raised AER, duration of diabetes was significantly longer, blood pressure (BP) was significantly greater and age of onset was lower in the micro-albuminuria group. Blood pressure was significantly elevated only in the patients with AER of 70-200 micrograms/min; there was a linear trend for BP to rise as AER increased. Stepwise logistic regression analysis indicated that duration of diabetes (P less than 0.0001), age of onset of diabetes (P less than 0.005) and current glycaemic control (HbA1) (P less than 0.01) were risk factors for micro-albuminuria. The association with a rising blood pressure appears to be secondary to the renal involvement. In this cross-sectional study an association of micro-albuminuria with a raised GFR could not be demonstrated. PMID- 2307093 TI - Fibrocalculous pancreatic diabetes and obesity. AB - Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes secondary to chronic pancreatitis that is found in tropical countries. Most patients with FCPD are lean and many are frankly undernourished. Four patients with FCPD who were obese are reported in this paper and this is the first report of obesity in FCPD patients. PMID- 2307094 TI - Prevention of overt diabetes and insulitis in NOD mice by a single BCG vaccination. AB - A single intravenous injection of 0.25-1 mg of live BCG organisms at approximately 10 weeks of age produced a potent suppression of insulitis and overt diabetes in non-obese, diabetes-prone (NOD) female mice. Injection of 1 mg of BCG into younger mice, aged 5 weeks, was also very suppressive but the injection into older mice of 15 weeks was somewhat less suppressive. Spleen cell transfer from the BCG-vaccinated NOD mice prevented the occurrence of overt diabetes in the recipients, while the transfer from untreated donors did not. This indicates the generation of some type of suppressor cells in the BCG vaccinated mice. PMID- 2307095 TI - Cardiac function and sympathetic activity in young diabetics. AB - This study was aimed at evaluating cardiac function, both systolic and diastolic, in young type 1 diabetics with a mean duration of the disease of 10.9 +/- 6 years and without evidence of cardiac autonomic neuropathy and micro- or macroangiopathy. Thirteen diabetics, with good metabolic control, and 10 normal matched subjects were studied by echocardiography at rest and by radionuclide ventriculography both at rest and during effort. The level of plasma catecholamines was also determined. The echocardiographic data were comparable in the two groups. Scintigraphic data showed an increased peak ejection and peak filling rate (P less than 0.001) in diabetics while the other indices of cardiac function were comparable. Norepinephrine (P less than 0.01) and epinephrine (P less than 0.001) were higher in diabetics. A hypothesis is formulated that the higher indices of flow velocities in type 1 diabetics are supported by a sympathetic overactivity. PMID- 2307096 TI - [Malaria prophylaxis of West German travelers to Africa]. AB - From May 1985 to July 1988, 11,445 German residents who had travelled to Africa filled in a questionnaire during the return flight and a second questionnaire sent to them 3 months later. 92.6% of the travellers had been on holiday and 99.3% of these holiday-makers were aware of the risk of malaria. Before and during their stay in the tropics 10,955 travellers (95.7%) had taken the chemoprophylaxis correctly, though in some instances the drugs prescribed were not in accordance with the guidelines existing at the time. However, 3227 of them (35.5%) discontinued the drugs too early, i.e. less than four weeks after their return. Only 4.3% of the travellers had taken proper precautions against mosquito bites. In view of the ever increasing numbers of people travelling to countries where malaria is endemic, doctors and travelers should be provided with more information and should be given more consistent advice on malaria prophylaxis. PMID- 2307098 TI - [Plant immunostimulants]. PMID- 2307097 TI - [Fatal complications in endoscopic papillotomy]. AB - Medicolegal investigations for possible malpractice were instituted into the death of three patients (two women, aged 59 and 75 years, one man, aged 81 years) after endoscopic papillotomy. In one case the accusation of malpractice had been made by a relative, in the other two the enquiry had been undertaken because the attending doctors had entered the cause of death as "unexplained" on the death certificate. In one patient oesophageal rupture had occurred; in the other two papillary bleeding, with perforation in one, had taken place. Forensic expert opinion failed to find malpractice as the cause of death. There had been the correct indications for the procedure and the patients had been fully informed. Taking into consideration the possible complications of this procedure, it is important to note that insufficient explanations and inadequate experience of the doctor, as well as insufficient capacity for undertaking an emergency operation, may lead to damages being awarded, especially under civil law. PMID- 2307099 TI - [The plastic laryngoscope]. PMID- 2307100 TI - [Chronic ventricular aneurysm. The sensitivity and specificity of persistent ST-T elevations on the electrocardiogram]. AB - The value of persistent ST-T elevations in the standard 12-lead ECG for the diagnosis of left-ventricular aneurysm (VA) was retrospectively analysed for 200 patients (171 males and 29 females) who had sustained a myocardial infarction at least 12 weeks previously. 105 patients (group 1) had a left-ventricular aneurysm confirmed by ventriculography; in 95 patients (group 2) an aneurysm had been excluded by ventriculography. Persistent ST-T elevations were present in 98 patients of group 1 (sensitivity 93.3%) and in 26 of group 2 (specificity 72.6%). In the 26 patients without VA, ST-T elevations occurred in at most three leads, but in 60 with aneurysm in four to nine leads. In addition, the area under the ST T elevations and its height 1 mm after onset of the elevation and its maximal height were measured. The sums of the values in the limb and chest leads were statistically significantly different between the two groups for all three parameters. These measurements thus contribute to a reliable differentiation between patients with and without VA. The results also emphasize the importance of the 12 standard leads in the diagnosis of VA. PMID- 2307101 TI - [Cushing's syndrome in CRF-producing mediastinal carcinoid]. AB - A 36-year-old patient developed marked pigmentation, marked myopathy and severe hypokalaemic alkalosis which at first pointed towards an ectopic ACTH syndrome. The dexamethasone test at a high dose indicated cortisol suppression. A mediastinal tumour was seen radiologically, but the sella was of normal size. Computed tomography provided indirect signs of a sellar space-occupying lesion which suggested an ectopic production of corticotropin-releasing factor (CRF) as cause of the Cushing's syndrome. CRF concentration in antecubital venous blood was markedly elevated to 280 ng/l. The mediastinal tumour was excised and proved to be a carcinoid histologically. Postoperatively the CRF concentration fell to 70 ng/l. An extract of the carcinoid contained 15.5 ng/g wet-weight of CRF and 254 ng/g wet-weight of beta-endorphin. The patient died 5 weeks postoperatively of sepsis with bilateral pneumonia. At autopsy the hypophysis was of normal size but showed nodular ACTH-cell hyperplasia. This was thus a case of Cushing's syndrome resulting from ectopic CRF production in a mediastinal carcinoid tumour. PMID- 2307102 TI - [Abnormal regulation of carnitine palmitoyltransferase in monozygotic twins as the cause of rhabdomyolysis]. AB - Severe myalgias, accompanied by reddish brown discolouration of the urine, occurred after strenuous exercise (all-day hockey competition) in a 21-year-old competitive athlete. Creatine kinase concentration was 1914 U/l, but there were no abnormal physical findings. The myalgias disappeared within three days. A biopsy from the lateral vastus muscle in the patient and his monozygotic twin brother showed normal total activity of carnitine palmitoyltransferase (CPT), but residual activity after inhibition with malonyl-CoA and Triton X-100 was clearly reduced in both brothers. Thus the illness was a rhabdomyolysis due to a, presumably inherited, abnormal regulation of CPT. The symptoms can be precipitated by fasting, marked physical exertion, cold or viral infection. PMID- 2307103 TI - [The understanding of sepsis in clinical medicine]. PMID- 2307104 TI - [Indications for lung transplantation]. PMID- 2307105 TI - Cardiovascular considerations in hypertension: effects of the angiotensin system. A seminar in print. PMID- 2307106 TI - [Primary venous thrombosis of the upper limbs]. PMID- 2307107 TI - [Myocardial sarcoidosis--glucocorticoid management of cardiomyopathy]. PMID- 2307108 TI - Characterization of antibodies to androgen-dependent secretory proteins of the mouse dorsolateral prostate. AB - The mouse prostate is an attractive model for studying the relationship between epithelial-mesenchymal interactions and the mechanism of androgen action because of the volume of information on tissue interactions in the development of the prostate of this species and the existence of a mutant mouse lacking functional androgen receptors (Tfm mouse). In this paper the major proteins of the mouse dorsolateral prostate (DLP) have been described, and antibodies to these proteins have been characterized. The two most abundant secreted proteins were of 110,000 115,000 (Mj1) and 55,000-62,000 (Mj2) mol wt. They were glycosylated, androgen dependent, and appeared to exist in an oligomeric complex. Antibodies raised against mouse DLP secretion reacted mainly with Mj1, Mj2, and a minor protein of 140,000 mol wt (Mn1). The antibodies were of a high titer and recognized these three mouse DLP proteins by Western blotting, immunoprecipitation, and immunocytochemical techniques. Mj1 and Mj2 were antigenically similar to proteins in the mouse coagulating gland and in the rat DLP, but were not found in other organs. Immunocytochemical staining of the DLP from intact mice revealed many ducts that were lined by a tall columnar epithelium whose cells stained intensely. However, ducts that were distended with luminal secretion had a low columnar epithelium that rarely showed intracellular staining. These marker proteins and the antibodies to them will be useful for detecting androgen dependent functional activity in tissue recombinant studies with a variety of experimental tissues. PMID- 2307109 TI - Effect of restricted feeding on the concentrations of growth hormone (GH), gonadotropins, and prolactin (PRL) in plasma, and on the amounts of messenger ribonucleic acid for GH, gonadotropin subunits, and PRL in the pituitary glands of adult ovariectomized ewes. AB - The effects of long term restricted feeding on the synthesis, storage, and release of GH, LH, FSH, and PRL were examined in adult ovariectomized ewes. Two groups of six ewes were fed a diet of either 1000 g/day (normal feeding) or 400 600 g/day (restricted feeding) hay for 20 weeks. Restricted feeding increased mean plasma GH concentrations and the amplitude of GH pulses, but did not affect GH pulse frequency. In contrast, mean plasma LH and FSH concentrations and LH pulse frequency were decreased by restricted feeding. Mean plasma PRL concentrations were unaffected by treatment. The levels of mRNA for GH in pituitary cytosol were increased by restricted feeding, but no changes were seen in mRNA levels of alpha-subunit, LH beta, FSH beta, or PRL. The pituitary contents of hormones measured did not change with the level of feeding. In conclusion, these data show that long term restricted feeding affects anterior pituitary function in adult ewes, presumably reflecting alterations in the secretion of hypothalamic releasing and inhibiting factors. PMID- 2307110 TI - Disparate effects of the prostaglandin synthesis inhibitors, meclofenamate, and flurbiprofen on monkey luteal tissue in vitro. AB - Intraluteal infusion of the prostaglandin (PG) synthesis inhibitor, sodium meclofenamate (Mec) causes premature luteolysis in rhesus monkeys. To evaluate further the actions of PG synthesis inhibitors in primate luteal function, we examined the in vitro effects of Mec and another inhibitor, flurbiprofen (Flur), on PG, cAMP, and progesterone (P) production by macaque luteal tissue obtained at midluteal phase of the menstrual cycle. First, collagenase dispersed luteal cells were incubated with 0-100 microM Mec or Flur, either alone or in the presence of 10 microM arachidonic acid (AA) to assess PGF2 alpha and PGE2 synthesis. Levels of both PGF2 alpha and PGE2 were stimulated (P less than 0.05) by AA (3.3- and 5.8-fold, respectively). Maximal suppression (P less than 0.01) of basal and AA stimulated PGF2 alpha and PGE2 synthesis was elicited by 1 microM Mec and Flur. Second, adenylate cyclase activity, measured by the conversion of alpha 32P-ATP to alpha 32P-cAMP, was monitored in luteal homogenates exposed to increasing doses of Mec and Flur either alone or with maximal stimulatory doses of hCG, PGE2, or PGI2. Mec elicited a dose-dependent reduction (P less than 0.01) in control activity (incubated with 50 microM GTP), as well as inhibiting hCG- and PG-stimulated activity. The presence of 100 microM Mec suppressed (P less than 0.01) hCG-, PGE2- and PGI2-stimulated activity to control levels, but had no effect on activity stimulated by GMP-P(NH)P or forskolin. In contrast, Flur at any dose did not alter control activity or that stimulated by hormonal or nonhormonal activators. Third, P production by dispersed luteal cells was quantified during exposure to 0, 1, and 100 microM Mec or Flur alone or with maximal stimulatory doses of hCG, PGE2, PGD2, 6 beta PGI1, PGA2, or dibutyryl cAMP (dbcAMP). All hormones and dbcAMP stimulated (P less than 0.01) P synthesis 2-3 fold over basal levels, except PGA2, which had no effect. The presence of 100 microM Mec reduced (P less than 0.01) basal P production by 62% and abolished (P less than 0.05) hCG-, PG-, and dbcAMP-induced stimulation. Conversely, neither 1 microM Mec nor either dose of Flur affected P synthesis in the absence or presence of hormones or dbcAMP. These data indicate that: 1) Mec and Flur are potent inhibitors of PG synthesis in primate luteal cells in vitro and 2) higher doses of Mec suppress PG- and gonadotropin-sensitive adenylate cyclase activity and P production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307111 TI - Interaction of three monoclonal antibodies with the nonactivated and activated forms of the estrogen receptor. AB - The 9S nonactivated oligomeric estrogen receptor from fetal guinea pig uterus interacts with the H222 monoclonal antibody (whose epitope is located in the hormone-binding domain) to yield an 11S complex and with the H226 monoclonal antibody (whose epitope is located in the A/B region, just N-terminal to the DNA binding domain) to yield a 9.4S complex. No reaction was detected with the D547 monoclonal antibody (whose epitope is located between the hormone-binding and DNA binding domains). In high salt gradients, the 11S oligomeric receptor-H222 complex dissociates to a 8S monomer-H222 complex and the 9.4S oligomeric receptor H226 complex to a 7S monomer-H226 complex plus the 4.5S monomer receptor not bound to the antibody. These observations suggest that the nonactivated oligomeric receptor contains more than one estradiol-binding subunit with a structure such that the H222 epitopes are fully accessible, the H226 epitopes are partially accessible, and the D547 epitopes are masked. The temperature-activated receptor reacts with the H226 antibody to yield two complexes that sediment at 7S and 9S in high salt gradients. The 9S complex corresponds to a receptor form complexed with more than one antibody molecule; therefore, this suggests the formation of a receptor homodimer where the two H226 epitopes are exposed. However, a single 8S peak is observed when the H222 antibody reacts with the activated receptor, suggesting that only one H222 epitope is accessible in the dimeric receptor. In addition, binding to the H222 antibody before activation prevents dimerization. Thus, the H222 appears to be close to the dimerization domain. The activated receptor reacts with the D547 antibody to yield a 8S complex that apparently contains only one antibody molecule. On the other hand, the receptor extracted from nuclei was found to be a single 5.5S form with the same immunological characteristics as the receptor activated in cytosol. In conclusion, interaction of these monoclonal antibodies with the different forms of the estrogen receptor reveals a structural transformation during activation, with a concomitant change in the exposure of the receptor functional domains. PMID- 2307112 TI - The stimulation of uterine complement component C3 gene expression by antiestrogens. AB - We have previously demonstrated that complement component C3 is regulated by estradiol in the rat uterus. The antiestrogens tamoxifen, LY117018, and LY156758 exert both agonist and antagonist effects on the immature rat uterus. In this study, these three antiestrogens also stimulated an increase in the synthesis and secretion of C3. The combination of LY117018 and estradiol did not increase C3 to a greater extent than LY117018 alone, which suggests a similar mechanism of regulation. The regulation may be transcriptional since both estradiol and tamoxifen increase the concentration of C3 mRNA. Results of in situ hybridization revealed that the increase in C3 mRNA occurred in the luminal epithelial cells. Although the induction by estradiol and the antiestrogens was similar in most aspects, the time course for tamoxifen-stimulated synthesis differed from estradiol in that the time required to achieve maximal concentrations of C3 was delayed by 12 h with tamoxifen. This pattern did not appear to be related to the time it took to convert tamoxifen to 4-hydroxytamoxifen since the C3 response for these antiestrogens were identical. The antiestrogen-stimulated increase in C3 synthesis and mRNA concentration was prevented by the co-administration of progesterone lending support to the hypothesis that the antiestrogens regulate C3 synthesis via a mechanism similar to estrogen. PMID- 2307113 TI - The proliferative effect of "anti-androgens" on the androgen-sensitive human prostate tumor cell line LNCaP. AB - The effect of steroidal and nonsteroidal "anti-androgens" on the proliferative capacity of androgen-sensitive LNCaP-FGC human prostate tumor cells in culture was studied using charcoal-dextran stripped human serum-supplemented media. Cyproterone and medroxyprogesterone acetates, flutamide, hydroxyflutamide, and anandron (R23908) were administered alone at concentrations between 3 X 10(-12) and 3 X 10(-6) M. Results indicated that although medroxyprogesterone induced maximal proliferation at 3 X 10(-9) M, the other "anti-androgens" (with the exception of flutamide that was ineffective) were effective at 3 X 10(-8) M and higher concentrations; the amplitude of the proliferative response by these compounds was comparable to that elicited by estradiol-17 beta (3 to 5-fold over control). None of the anti-androgens tested triggered the shutoff effect characteristic of androgen action. When 3 X 10(-10) M DHT and the above mentioned anti-androgens were administered simultaneously, a synergistic pattern was seen; on the contrary, 3 X 10(-8) M DHT cancelled the proliferative effect of each of the anti-androgens when administered simultaneously. The relative binding affinity of these anti-androgens to androgen receptors present in LNCaP-FGC cells did not correlate well with their proliferative efficiency. The data collected were interpreted within the premises of the negative control hypotheses for the regulation of cell proliferation in metazoans. Within those premises, results became compatible with the notion that first, "anti-androgens" elicited the proliferation of androgen-sensitive cells by neutralizing the effect of a serum borne inhibitor (androcolyone-I); this event seems not to be mediated by androgens receptors. Second, anti-androgens did not trigger a proliferative shutoff response like androgens do, i.e. the proliferative pattern induced by anti-androgens was comparable to that elicited by estrogens and progestins. Third, when administered simultaneously with 3 X 10(-10) M DHT, anti-androgens behaved synergistically. Fourth, the DHT-induced shutoff effect consistently overrode the proliferative effect generated by anti-androgens and estrogens when added alone. Finally, taken together these results raise important questions regarding the therapeutic role of anti-androgens in prostate cancer. PMID- 2307114 TI - Structure-function relationships for full-length recombinant parathyroid hormone related peptide and its amino-terminal fragments: effects on cytosolic calcium ion mobilization and adenylate cyclase activation in rat osteoblast-like cells. AB - PTH-related peptide (PTHrP) may be a major cause of the humoral hypercalcemia of malignancy. The circulating form of PTHrP is unknown, but mRNA analysis of tumor tissue suggests that multiple forms of PTHrP may exist. Therefore, we examined the ability of the full 141-amino acid protein as well as 2 amino-terminal fragments, PTHrP-(1-34) and PTHrP-(1-74), to increase cytosolic calcium ion concentrations ([Ca2+]i; assessed by aequorin luminescence) and stimulate cAMP accumulation in osteoblast-like rat osteosarcoma cells (ROS 17/2.8). PTH and all PTH-related peptides examined increased [Ca2+]i and cAMP in a concentration dependent manner. The [Ca2+]i response to PTHrP-(1-34) closely resembled that to rat PTH-(1-34); both peptides produced biphasic responses. However, the responses to the longer PTHrP fragments generally were not biphasic. There were no significant differences among the three PTHrP forms in increasing [Ca2+]i or stimulating cAMP accumulation, although PTHrP-(1-74) was consistently weaker than the other two PTHrP peptides. PTHrP-(1-34) was more potent than rPTH-(1-34), which, in turn, was more potent than human PTH-(1-34) in increasing [Ca2+]i. However, PTHrP-(1-34) was not consistently more potent than either human PTH-(1 34) or rat PTH-(1-34) in stimulating cAMP accumulation. The inhibitory PTH analog bovine PTH-(3-34) attenuated both cAMP and [Ca2+]i responses to PTHrP-(1-34), but bovine PTH-(7-34) only reduced the [Ca2+]i response. Our data are generally consistent with PTHrP's acting through the PTH receptor, but differences in the effects of inhibitory PTH analogs on PTH and PTHrP action suggest as yet unexplained complexities, such as the existence of a PTH/PTHrP receptor family. PMID- 2307115 TI - Localization of vasopressin binding sites in rat tissues using specific V1 and V2 selective ligands. AB - Arginine vasopressin (AVP) acts on at least two receptor types, classified on the basis of their second messengers. The V1 receptor acts via mobilization of intracellular calcium through phosphatidylinositol hydrolysis and influences blood pressure and hepatic glycogenolysis. The V2 receptor acts via cAMP through activation of adenylate cyclase and causes antidiuresis. Previous studies of the different AVP receptors have been hampered by the use of nonselective radioligands, such as [3H]AVP (which binds to all types of V1 and V2 receptors, certain oxytocin receptors, and neurophysins) as well as the difficulty of measurement of second messengers. This paper describes the use of selective V1 and V2 radioligands with in vitro autoradiography to study V1 and V2 binding sites in rat tissues. [125I][1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 7-sarcosine] arginine vasopressin ([125I][d(CH2)5,Sarcosine7]AVP), a selective V1 antagonist radioligand, bound to regions of the brain, testis, superior cervical ganglion, liver, blood vessels, and renal medulla. Pharmacological characterization of [125I][d(CH2)5,Sarcosine7]AVP binding was consistent with that expected for binding to V1 receptors. There was no specific binding demonstrable to pituitary, renal glomeruli, gut, heart, spinal cord, ovary, adrenal medulla, or adrenal cortex. [3H]1-deamino [8-D-arginine] vasopressin [( 3H]DDAVP), a potent V2 receptor agonist radioligand, was used to study V2 receptors. Specific binding was only identified in the kidney consistent with the known distribution of antidiuretic V2 receptors on renal collecting tubules. No binding was demonstrated on endothelium or liver where DDAVP might influence clotting factor release, nor in the brain, spinal cord, sympathetic ganglia, heart or vascular smooth muscle, regions where DDAVP might cause vasodilatation. These studies demonstrate the use of these radioligands to study V1 and V2 receptors in a variety of tissues. Also, since these ligands are selective they are of particular use to study the different receptor subtypes in tissues where V1 and V2 receptors coexist, such as in the kidney. PMID- 2307116 TI - Reduced adipsin expression in murine obesity: effect of age and treatment with the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. AB - Adipsin gene expression is greatly diminished in certain forms of genetic and acquired obesity. In the present study we evaluate the time course for the development of adipsin deficiency in obesity and its regulation by the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. Previously, it was unknown whether adipsin deficiency occurred before or after the development of massive obesity. In the first series of experiments in which mice were treated with monosodium glutamate (MSG) for the first week of life, we demonstrate that adipsin deficiency occurs early in the development of MSG-induced obesity as evidenced by decreased circulating adipsin concentrations by 1 week of age and deficient adipsin mRNA levels in white adipose tissue (WAT) by 2 weeks. In db/db mice, diminished circulating adipsin was noted at 2 weeks of age. In both models, decreased adipsin gene expression precedes the development of marked obesity. Little is known about the factors which regulate adipsin gene expression in obesity. Common to the ob/ob, db/db and MSG models is diminished thermogenesis and sympathetic nervous system activity. In a second series of experiments we sought to determine whether adipsin deficiency in obesity could be corrected by treatment with ephedrine and caffeine (E+C), a sympathomimetic-thermogenic mixture previously shown to increase thermogenesis and reverse obesity in some models. In the present study, E+C treatment of MSG obese mice reversed obesity and markedly increased serum adipsin and adipsin mRNA levels in WAT and brown adipose tissue (BAT). In ob/ob mice, however, E+C treatment produced a negligible increase in adipsin mRNA levels in WAT and BAT as well as serum adipsin concentrations and this correlated with only a very small decrease in obesity. Thus, the ability of E+C to increase adipsin gene expression correlated with its ability to reverse obesity in these two models. Finally, the effect of E+C on adipsin gene expression may not be exerted directly on the fat cell since treatment of cultured 3T3-F442A adipocytes and isolated rat adipocytes in primary culture produced no effect on adipsin mRNA or secreted protein despite a lipolytic effect as measured by increased glycerol release. In summary, decreased adipsin gene expression occurs early in the development of MSG and db/db obesity and is markedly increased in the MSG model by the sympathomimetic-thermogenic drug mixture, E+C, which also reverses obesity. Elucidation of the factors responsible for these effects may enhance our understanding of fat cell gene regulation and obesity. PMID- 2307117 TI - Further characterization of protein kinase-C subspecies in the hypothalamo pituitary axis: differential activation by phorbol esters. AB - Three forms of protein kinase-C were resolved from rat hypothalamus: types I, II, and III, which correspond to the brain subspecies gamma, beta, and alpha, respectively. The rat pituitary contains the type II and type III enzymes but not type I. The hypothalamic type II enzyme is a mixture of beta I (24%) and beta II (76%), whereas the pituitary type II enzyme contains most likely only the beta II enzyme. The hypothalamic type I enzyme is relatively resistant to activation by the tumor-promoting phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) or diacylglycerol (DG). Both type II and type III enzymes of hypothalamus and pituitary were responsive to TPA or DG stimulation, with the hypothalamic subspecies being less responsive. Binding of [3H]phorbol 12,13-dibutyrate revealed different binding properties among the various subspecies, with the pituitary enzymes displaying higher affinities than the respective hypothalamic counterparts. The results demonstrate heterogeneity in protein kinase-subspecies expression and responsiveness to TPA and DG and suggest specific roles for the subspecies in the hypothalamo-pituitary axis. PMID- 2307118 TI - The effects of sexual maturation and altered steroid synthesis on the production and route of secretion of inhibin-alpha from the rat testis. AB - This study has determined the route of secretion of inhibin-alpha into blood by the rat testis during sexual maturation, and in adult animals in which Leydig cell steroidogenesis was stimulated with human CG (hCG) or suppressed with aminoglutethimide. In each rat, inhibin-alpha levels were measured in samples of testicular (TV), spermatic (SV), and peripheral (PV) venous blood plasma, and in testicular interstitial fluid (IF). The IF and TV plasma reflect inhibin-alpha secretion via the base of the Sertoli cell while that secreted via the apex of the Sertoli cell (which is resorbed from the rete testis) was determined from the difference between SV and TV levels of inhibin-alpha. During sexual maturation, inhibin-alpha levels in IF and all plasma samples declined from maximal values at 28 days of age to minimal values at 100 days of age, in contrast to testosterone levels which showed the reverse pattern. There was a major change with age in the route of secretion of inhibin-alpha from the testis into blood. In immature (28 35 days) rats, most inhibin-alpha (58-65%) leaving the testis in blood was derived from that secreted via the base of the Sertoli cell with a relatively small contribution (35-42%) from apically-secreted inhibin-alpha. However, the latter made a progressively increasing contribution between 45 and 100 days of age (adults) and in adult rats the vast majority of inhibin-alpha (95%) leaving the testis in blood was derived from apically-secreted inhibin-alpha. This change was due primarily to a progressive reduction with age in the secretion of inhibin alpha via the base of the Sertoli cell, a change which was confirmed by inhibin bioassay. Stimulation of steroidogenesis in the adult testis with hCG significantly increased inhibin-alpha and testosterone levels in IF and all plasma samples. The concomitant administration of hCG and aminoglutethimide (to block steroidogenesis) prevented the hCG-induced increase in testosterone levels, but still led to significant increases in inhibin-alpha secretion which were comparable to those seen with the use of hCG alone. The administration of aminoglutethimide (AMG) on its own did not alter the inhibin-alpha secretion profile from that seen in controls, but it did significantly reduce the levels of testosterone in all fluids. In rats treated with hCG +/- AMG there was a small change in the route of secretion of inhibin-alpha into blood, with an increased contribution (24-37%) from inhibin-alpha secreted via the base of the Sertoli cell, when compared with controls (7-16%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2307119 TI - Cortisol enhances the anabolic effects of insulin-like growth factor I on collagen synthesis and procollagen messenger ribonucleic acid levels in cultured 21-day fetal rat calvariae. AB - We examined the ability of cortisol to modulate the stimulatory effects of recombinant human insulin-like growth factor-I (IGF-I) on collagen synthesis, procollagen messenger RNA (mRNA) levels and DNA synthesis in 21-day fetal rat calvariae maintained in serum-free organ culture for 24-96 h. Collagen synthesis was quantitated by measuring the incorporation of [3H]proline into collagenase digestible protein (CDP) and alpha-1(I) procollagen mRNA transcripts were assessed by Northern blot analysis. Cell replication was quantitated by measuring the incorporation of [3H]thymidine into bone. As described previously, 100 nM cortisol had a biphasic effect on CDP labeling, increasing CDP after 24 h and decreasing CDP after 48, 72, and 96 h of culture. IGF-I alone increased CDP labeling by 1.6-fold after 24 h and by 2-fold after 48 or 72 h of culture, and cortisol potentiated this anabolic effect. In the presence of 100 nM cortisol, IGF-I increased CDP labeling by 2.6-fold after 24 h, by 5-fold after 48 h, and by 8-fold after 72 h of culture. A higher concentration of cortisol (1000 nM) also potentiated the IGF-I response on CDP labeling after 96 h of culture. In the presence of 100 nM cortisol, concentrations of IGF-I lower than 10 nM consistently increased CDP labeling and the percent collagen synthesized whereas these concentrations were not always effective without cortisol. PTH, which like cortisol decreased basal CDP labeling, did not enhance the stimulatory effects of IGF-I. Cortisol also enhance the stimulatory effects of IGF-I on alpha-1(I) procollagen mRNA levels indicating that the potentiation of CDP labeling occurs via a pretranslational mechanism. IGF-I had little effect on the incorporation of [3H]thymidine into bone except in the presence of cortisol. Nevertheless, the ability of cortisol to potentiate the stimulatory effect of IGF-I on CDP labeling was independent of cell replication since the enhancement persisted in the presence of aphidicolin, a DNA synthesis inhibitor. Our findings show that physiological concentrations of cortisol can modulate the responsiveness of cells within cultured fetal rat calvariae to the anabolic effects of exogenous IGF-I. PMID- 2307120 TI - Neuromedin-N is not released with neurotensin from rat ileum. AB - Neuromedin-N (NN) and neurotensin (NT) were shown recently to be encoded in the same precursor molecule. Colocalization and corelease of ileal NT and NN have not yet been demonstrated and were investigated in the rat using antisera that separately recognized intact NT and NN in ileal extracts. Immunofluorescence labeling of full thickness ileal wall revealed that NN-positive fluorescence was only found in the N-cells. However, only 50% of the N-cells also contained NN like immunoreactivity (NN-LI). This was associated with a level of extractable NN that was 5-fold lower than that of NT. Corelease of NN- and NT-LI was investigated with the isolated, vascularly perfused jejunoileum model by using various substances that were described as potent stimulants of NT release in vivo. Luminal infusion of mixed nutrients, oleic acid (100 mM), glucose (5%), and taurocholic acid (1%) induced a well sustained release of NT, with plateau secretion of about 200%, 120%, 300%, and 700% above basal, respectively. Vascular bombesin (10(-7) M) and carbachol (10(-5) M) provoked a biphasic release of NT, consisting of a transient rise (approximately 600% above basal) followed by a less pronounced but sustained response. HPLC analysis of portal effluent revealed that 70-80% of NT-LI was intact NT. NN-LI was not coreleased with NT even upon vascular coinfusion of phenanthroline, which markedly protected exogenously infused NN. The coexistence but lack of corelease to any significant degree of NN with NT suggests different fates of these two precursor-related peptides within the ileal mucosa. PMID- 2307121 TI - Effect of 1,25-dihydroxyvitamin D3 on induction of chondrocyte maturation in culture: extracellular matrix gene expression and morphology. AB - Chondrocytes, derived from a tissue that remains as permanent hyaline cartilage in vivo (embryonic chicken caudal sterna) were treated with 10(-8) to 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. These nonadherent rounded chondrocytes acquired an adherent, polygonal morphology in a dose-dependent fashion with 1,25(OH)2D3 treatment. During the first 4 days of 1,25(OH)2D3 treatment cell flattening was associated with a 10-fold increase in beta-actin and fibronectin and their corresponding messenger RNAs (mRNAs). After adherence over the 12 days of continuous hormone treatment, a 2- to 4-fold increase in DNA synthesis and DNA accumulation were observed for the highest hormone dose (10(-8) M). Over the same time course total collagen synthesis decreased 35-50% primarily due to decreased type II collagen synthesis, which accompanied comparable decreases in its mRNA. In contrast, both alpha 1(I) and alpha 2(I) showed a continuous 5- to 10-fold increase; however, type I collagen protein synthesis remained undetectable, indicating translational control of the type I collagen synthesis. alpha 1(X) mRNAs showed a 2- 3-fold increase after 12 days of hormone treatment, and its polypeptide was clearly detected by sodium dodecyl sulfate polyacrylamide gel analysis. Type IX collagen synthesis showed a 2-fold increase in synthesis and its mRNA levels during the first 4 days of 1,25(OH)2D3 treatment but thereafter had levels comparable to control cultures. Analysis of proteoglycan synthesis and core protein mRNA levels showed there was a 2-fold increase in core protein mRNAs while proteoglycan synthesis, as assessed by 35S incorporation, showed only a 10 20% increase. Direct hormone effects vs. those secondary to altered cellular morphology were determined by blocking cell adherence by growth of the 1,25(OH)2D3-treated cultures on bacteriological petri dishes. All of the observed effects on cytoskeletal and collagen mRNAs were blocked except the elevations observed in proteoglycan core protein and alpha 1(IX) mRNAs. DNA contents in hormone-treated cultures also remained elevated. These results suggest that 1,25(OH)2D3 both activates and suppresses specific genes, promoting chondrocyte maturation toward a more hypertrophic phenotype. However, prevention of the initial morphological alterations that are induced by 1,25(OH)2D3 blocks many of the subsequent changes in connective tissue expression. PMID- 2307122 TI - Growth hormone aggregates in the rat adenohypophysis. AB - Although it has been known for some time that GH aggregates are contained within the rat anterior pituitary gland, the role that they might play in pituitary function is unknown. The present study examines this issue using the technique of Western blotting, which permitted visualization of 11 GH variants with apparent mol wt ranging from 14-88K. Electroelution of the higher mol wt variants from gels followed by their chemical reduction with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. With the blot procedure we found 1) that GH aggregates greater than 44K were associated with a 40,000 x g sedimentable fraction; 2) that GH aggregates were not present in glands from thyroidectomized rats, but were in glands from the thyroidectomized rats injected with T4; 3) that GH aggregates were uniquely associated with a heavily granulated somatotroph subpopulation isolated by density gradient centrifugation; and 4) that high mol wt GH forms were released from the dense somatotrophs in culture, since treatment of the culture medium with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. Taken together, the results show that high mol wt GH aggregates are contained in secretory granules of certain somatotrophs and are also released in aggregate form from these cells in vitro. PMID- 2307123 TI - Generation of intercellular heterogeneity of growth and function in cloned rat thyroid cells (FRTL-5). AB - The most characteristic hallmarks of human nodular goiters are nodular growth and heterogeneity of structure and function between different areas of the same goiter. In search of the earliest detectable stage of thyroid heterogeneity we have observed doubling times, TSH dependency, and thyroglobulin production in colonies formed from individual FRTL-5 cells growing as monolayers in slide flasks. Single cells and the colonies derived thereof were followed on photographs taken daily until confluence. We observed that each cell had its individual stable multiplication rate throughout the observation period. This was true for all TSH doses tested (0.625-10 mU/ml). A wide range of doubling times (20 h to almost infinite) in the individual cells was observed. The mean growth velocity of subcloned cell lines was highly reproducible in consecutive passages, although a minority of cells escaped this rule. Cells with either high or low thyroglobulin content occurred in clusters, indicating again that specific traits tend to remain stable in the offspring. We conclude that a highly individual growth program, unrelated to mutation, appears to be switched on at the very moment a cell is generated and that this program is passed on to the majority of the offspring, with a minority of cells acquiring qualities differing from those of their sister cell. Therefore, goiter heterogeneity may be the in vivo amplification of a natural phenomenon occurring in all growing cells. Monoclonal adenomas in vivo and nontransformed immortal cell lines in vitro may represent the far end of the large spectrum of individual growth potency among normal thyrocytes. PMID- 2307124 TI - 5'-Deiodination in rat hepatocytes: effects of specific flavonoid inhibitors. AB - 5'-Deiodination of T4 or rT3 in the presence of flavonoids was studied in freshly isolated suspended rat hepatocytes. Flavonoids, a novel group of synthetic deiodinase inhibitors, were designed to act as T4 antagonists. 5'-Deiodination of the prohormone T4 to the thyromimetically active T3 is an essential first step in controlling thyroid hormone action. Hepatocytes were incubated with either 2 microM T4 or 2 microM [125I]rT3 as 5'-deiodinase substrates in the absence and presence of inhibitors (0.1-100.0 microM). T3 production from T4 was determined by T3 RIA, and [125I]iodide release from [125I]rT3 was alternatively used as a technically more simple and rapid but sensitive deiodinase assay. Aurones and flavones inhibited both T4 5'-deiodination and rT3 5'-deiodination, with half maximal inhibitor concentrations from 3-45 microM. Aurones were equally potent in both assays. 3-Methyl-flavones, designed as rT3 analogs, were more active by a factor of 3-5 with T4 5'-deiodination than with rT3 5'-deiodination, with the exception of one relatively cell-toxic compound. Hepatocyte viability was controlled by trypan blue dye exclusion as well as by measuring gluconeogenesis from exogenously added 10 mM lactate. Some of the flavonoids inhibited gluconeogenesis at concentrations that had no effect on trypan blue dye exclusion. Flavonoid inhibitors reduce 5'-deiodinase activity in intact hepatocytes in concentrations equimolar to those of substrates. Therefore, synthetic flavonoids may be suitable substances for further study of iodothyronine physiology or, after modification, could be useful as a new class of antiiodothyronine drugs. PMID- 2307125 TI - Characterization of the transferrin receptor in UMR-106-01 osteoblast-like cells. AB - The accumulation of iron or aluminum can cause metabolic bone disease, but the mechanisms by which these agents affect bone metabolism remain uncertain. Since transferrin (Tf) can bind several different metals in plasma, equilibrium radioligand binding studies were performed to identify and characterize the Tf receptor in UMR-106-01 osteoblast-like cells; the role of Tf as a modifier of metal-induced changes in cell proliferation was also examined. Osteoblast-like cells grown in serum-free medium have approximately 40,000 Tf receptors on the cell membrane. Tf receptor expression increases during iron depletion and decreases with iron supplementation; the number of Tf receptors was also inversely related to both cell density and the rate of cell proliferation in vitro. Physiological levels of unsaturated Tf (5 microM) enhanced DNA synthesis in osteoblast-like cells maintained in serum-free medium, as measured by the incorporation of tritiated thymidine into DNA. Although neither 10 microM iron (Fe) nor 10 microM gallium (Ga), a known antiproliferative agent, altered DNA synthesis in UMR-106-01 cells during 48-h incubations in serum-free medium, both agents reduced the rate of DNA synthesis when added to serum-free medium containing 5 microM apo-Tf. Decreases in the incorporation of [3H] thymidine into DNA were also noted in osteoblast-like cells incubated for 48 h with 3 microM partially saturated iron Tf or gallium Tf. The results indicate that osteoblast like cells have a single class of membrane receptors for Tf and that the regulation of Tf receptor expression in UMR-106-01 cells is similar to that in other cell types. The uptake of iron and gallium via the Tf-receptor complex can affect osteoblast proliferation, and such a mechanism may contribute to the bone cell toxicity of various metals. PMID- 2307126 TI - Analysis of the role of basic fibroblast growth factor in growth and differentiation of transplanted fetal rat paws and intestines. AB - Paws and intestinal segments from 16-day-old rat fetuses were transplanted bilaterally under the kidney capsule of adult female hosts and grown there for different periods of time. The direct effects of an antiserum to bovine basic fibroblast growth factor (bFGF) and of recombinant bFGF on growth and tissue differentiation in the transplants were evaluated by infusing them into the right renal artery via a catheter attached to an osmotic minipump. Infusion of the antiserum into the right kidney of intact hosts for 6 or 10 days did not affect either growth of the paws or bone differentiation in them. By contrast, the anti FGF serum significantly inhibited the growth of intestinal transplants and caused slight retardation of villus differentiation. We presume that this inhibition resulted from neutralization of the bFGF produced within the transplants, as infusion of nonimmune rabbit serum had no such effects on the intestinal segments. In hypophysectomized hosts growth of both types of transplants was greatly reduced, and tissue differentiation was retarded, presumably reflecting low serum insulin-like growth factor-I levels. Infusion of the recombinant bFGF (5 micrograms/rat.day) into the hypophysectomized hosts stimulated growth of the paws and promoted ossification of the phalanges, but not the carpals. Intestinal growth was not affected by bFGF, and villus development was not restored. These results indicate that fetal rat structures are differentially dependent on and responsive to bFGF for growth and differentiation. These findings, when considered in relation to our previous results with transplanted 10-day-old rat embryos, indicate that growth and tissue differentiation during the embryonic period of rat development are more dependent on bFGF than are these processes in the fetal period. PMID- 2307127 TI - The parathyroid hormone-related protein stimulates human osteoblast-like cells to secrete a 9,000 dalton bone-resorbing protein. AB - The mechanism by which parathyroid hormone-related protein (PTH-RP) stimulates bone resorption is not known. Like certain other resorbing agents it may act to release bone-resorbing cytokines from the osteoblast. To examine this hypothesis, we used serum-free conditioned media (CM) from SAOS II cells incubated with 10( 8) M h(1-74) PTH-RP for 48 h. Treated CM contained substantially more bone resorbing activity (BRA) in the fetal-rat long-bone assay than CM from untreated cells (2.17 +/- 0.21 vs 1.38 +/- 0.16 fold stimulation over basal [f]; p less than 0.05]. After centrifugation and dialysis, 1 liter of treated CM contained a total BRA of 7102 ngeq b(1-34) PTH with a specific activity (SA) of 447 ngeq b(1 34) PTH/mg protein. Treated CM did not stimulate the ROS assay and the cytokines PGE2, TGF-alpha, EGF, GM-CSF and IL-1 were present in low concentrations. The BRA was heat sensitive. Ultrafiltration revealed that 97% of the BRA was in a 3-30 kD fraction. Further purification was achieved by sequential reverse phase HPLC and size exclusion-HPLC (SE-HPLC). A single fraction containing BRA from SE-HPLC was purified 277-fold to a SA of 123,810 ngeq b(1-34) PTH/mg protein and had an apparent MW of 9 kD. SDS-PAGE revealed 4 bands in this SE-HPLC fraction with 1 band at 9 kD unique to that fraction. PTH-RP may cause bone resorption in part by stimulating the release of a 9 kD protein from osteoblasts which is responsible for activating osteoclasts. PMID- 2307128 TI - Role of Lugol dye endoscopy in the diagnosis of early esophageal cancer. AB - To evaluate the role of Lugol dye endoscopy in diagnosing early esophageal cancer, we reviewed findings of dye endoscopy and those of conventional endoscopy in 17 early esophageal cancers that were demonstrated as unstained areas on dyeing with Lugol solution. Histologically, all 17 lesions were squamous cell carcinomas; 10 lesions being mucosal carcinomas, the remaining 7 lesions mucosal carcinomas spreading beyond the epithelial layer. The lesions ranged from 0.7 to 4.0 cm in size. Abnormal findings were noted under conventional endoscopy in all but 3 lesions diagnosed only by postoperative pathohistology, regardless of the size and depth of the invasion. Under conventional endoscopy, the following types of morphological changes were noted in 8 (57.1%) of the 14 lesions: slight elevation (1 lesion), depression (6 lesions), and deformed arc (1 lesion). A color change was noted endoscopically in 12 of the 14 lesions (85.7%), this change being redness in all 12 lesions. The unstained area on the resected specimen was consistent with the size of the lesion that was determined by using serially sectioned blocks in all cases. Moreover, the former completely (100%) coincided with the histological area where PAS reaction was weak. In conclusion, under conventional endoscopy, a color change such as redness is an important indicator of minute or superficial esophageal cancer, as is such morphological change as depression, elevation or deformed arc. On the other hand, Lugol dye endoscopy is very helpful in detecting esophageal cancer unassociated with any morphological or color change. It also provides accurate information about the extent of the cancer. PMID- 2307129 TI - Endoscopic placement of biliary endoprostheses in patients with endoscopically unextractable common bile duct stones. A long-term follow up study of 26 patients. AB - Endoscopic sphincterotomy for removal of stones from the common bile duct, in particular in high-risk patients is an established procedure. However, the size of the stones and the appearance of the terminal bile duct prior to sphincterotomy have an influence on the outcome. In the period 1984-1987, thirty four patients considered to be at high risk for surgery were treated endoscopically by insertion of a biliary endoprosthesis (15 cm long, 3.2 mm diameter) after unsuccessful attempts to remove common bile duct (CBD) stones following endoscopic sphincterotomy. These patients were admitted to the hospital with biliary colic, obstructive jaundice and/or cholangitis. Eight patients were lost to follow-up. The remaining patients comprised 20 females and 6 males, with a mean age of 81 years (range: 60-96). Five patients underwent surgical treatment for perforation (one patient, 11 months after insertion), persistent jaundice (one patient) or recurrent obstructive jaundice (endoprosthesis clogging in one, endoprosthesis dislodgement in two patients) 2 to 40 months after insertion. In one patient, recurrent obstructive jaundice was successfully treated by replacing the clogged endoprosthesis 4 months after the initial treatment. Ten patients died of unrelated causes (myocardial infarction, accident, etc.) 2 to 28 months after insertion. The remaining ten patients were still alive without symptoms after a median follow-up of 26 months. On the basis of these findings we therefore conclude that endoscopic insertion of a biliary endoprosthesis is a safe and effective treatment for huge CBD stones in high-risk patients in whom endoscopic sphincterotomy and attempts to remove the stones are not successful. PMID- 2307130 TI - Parietal cell carcinoma. A new differential diagnosis for submucosal gastric tumors. PMID- 2307131 TI - Detection of large intrahepatic cholangiectases in patients with primary sclerosing cholangitis by endoscopic retrograde cholangiography. AB - Cholangiographic features of primary sclerosing cholangitis are multiple strictures and alternating dilated and normal segments of both intra- and extrahepatic bile ducts. Formerly, intrahepatic cholangiectases have been shown only in explanted livers, but we now describe the presence of large intrahepatic cholangiectases in a 22-year-old male patient with primary sclerosing cholangitis, visualized using a balloon catheter at endoscopic retrograde cholangiography. Cholangiectases in this patient appear to have been caused by the disease and not as a result of prestenotic dilatations. To treat possible early complications of this condition, we recommend looking for these cholangiectases when diagnostic endoscopic retrograde cholangiography is performed in primary sclerosing cholangitis. PMID- 2307132 TI - Hemorrhage in the upper digestive tract caused by an aorto-esophageal fistula. AB - The case of a 75-year-old patient admitted to our Center with hematemesis is presented. At oral endoscopy a pulsating vegetative mass was found in the distal third of the esophagus, which aroused suspicion of an aortic aneurysm fistulized to the esophagus; this was confirmed by arteriography. He underwent two surgical procedures, the aneurysm being resected and replaced by an aortic prosthesis, and esophagectomy performed. The patient died of postoperative complications. The endoscopic appearance is shown. PMID- 2307133 TI - A 19-year-old female with blue rubber bleb nevus syndrome. Endoscopic laser photocoagulation and surgical resection of gastrointestinal angiomata. AB - A case of a blue rubber bleb nevus syndrome in a 19-year-old female patient with multiple cutaneous and gastrointestinal hemangiomata is described. Recurrent GI bleeding resulted in severe chronic anemia, which was successfully treated by endoscopic laser photocoagulation and surgical resection. Both forms of therapy had to be repeated 4 years later, the patient having been well in the meantime. This combined endoscopic and surgical approach might also improve the survival of patients with severe GI hemorrhage due to blue rubber bleb nevus syndrome. PMID- 2307134 TI - Tuberculous mediastinal adenopathy mimicking esophageal leiomyoma. PMID- 2307135 TI - Hiatal hernia causing an unusual complication of gastroscopy. PMID- 2307136 TI - What kind of non-bleeding visible vessel in a peptic ulcer needs aggressive therapy? Long-term clinical observation. AB - A total of 57 patients with peptic ulcers showing non-bleeding visible vessels were followed for 1-26 months (mean +/- SEM: 13.8 +/- 1.7 months). The age was 56.2 +/- 2.1 years (mean +/- SEM). Blood transfusion with a mean volume of 3.89 units was given. Twenty-five (25/57, 43.9%) patients had rebleeding episodes within one month. Seventeen (17/57, 29.8%) patients were submitted to operation or therapeutic endoscopy due to failure of hemostasis. We analyzed eight clinical parameters on admission of these patients with the aid of a stepwise logistic regression test. Advanced age (over 60), blood transfusion of more than 500 ml and shock were found to be independent predictors of rebleeding. Advanced age (over 60) and coffee ground material in the stomach were found to be independent predictors of ultimate failure of conservative management. We recommend aggressive (either operation or therapeutic endoscopy) rather than conservative management in a patient with a non-bleeding visible vessel who has any of the following characteristics on admission: age over 60, volume of blood transfusion over 500 ml, shock and coffee ground material in the stomach. PMID- 2307137 TI - Photoacoustic studies of non-radiative relaxation of excited states in melanin. AB - Photoacoustic measurements made at various chopping frequencies on dense acqueous melanin suspensions have revealed a significant dependence upon pH and redox state. It is shown that such behaviour, differing from the simple predictions of the Rosencwaig-Gersho theory, can be explained in terms of finite carrier diffusion and recombination times. The implications of these findings with respect to the amorphous semiconductor model proposed to describe the dynamic role of epidermal melanin are discussed. From the experimental data, values of physical parameters were calculated which allow a qualitative correlation between chemical states and electronic behaviour and, consequently, some aspects of the molecular biology of the melanosome, founded on a rigorous base. PMID- 2307138 TI - A network thermodynamic method for numerical solution of the Nernst-Planck and Poisson equation system with application to ionic transport through membranes. AB - Simple techniques of network thermodynamics are used to obtain the numerical solution of the Nernst-Planck and Poisson equation system. A network model for a particular physical situation, namely ionic transport through a thin membrane with simultaneous diffusion, convection and electric current, is proposed. Concentration and electric field profiles across the membrane, as well as diffusion potential, have been simulated using the electric circuit simulation program, SPICE. The method is quite general and extremely efficient, permitting treatments of multi-ion systems whatever the boundary and experimental conditions may be. PMID- 2307139 TI - The fluorescence properties of a DNA probe. 4'-6-Diamidino-2-phenylindole (DAPI). AB - Steady-state and dynamic fluorescence measurements have been performed on DAPI in solution and in complexes formed with a number of synthetic and natural polydeoxynucleotides. The decay of DAPI in buffer at pH 7 was decomposed using two exponentials having lifetime values of approximately 2.8 ns and 0.2 ns. The double exponential character of the decay was maintained over a large pH range from 3 to 9. At pH 1 the short component dominated, whereas at pH 12, only the long component was detectable. Two distinct spectra were associated with the two lifetime components; the short component was shifted to the red. The short lifetime component occurs in the presence of water. In water the excitation spectra depended on the emission wavelength and there was no viscosity dependence of the two forms. To explain these results we propose that there is a ground state conformer in which preferential solvation of the indole ring allows proton transfer in the excited state. DAPI complexed with polydeoxynucleotides retained most of the features of the decay of DAPI in solution. However, the complexes with fully AT-containing polymers stabilized the longer lifetime form of DAPI because the stronger binding enhanced solvent shielding. A gradual increase of the short lifetime component, which monitors dye solvent exposure, was obtained as the AT content was decreased. For polyd(GC) the decay was similar to that of free DAPI. PMID- 2307140 TI - SAXS study of the snake toxin alpha-crotamine. AB - alpha-crotamine is a small toxic protein (42 amino acid residues with three disulphide bridges) present in the venom of Crotallus durissus terrificus. Molecular parameters (Rg = 13.7 A, S = 3,000 A2, V = 9,200 A3 and Dmax = 40 A) were derived from SAXS curves obtained from a solution of this protein at pH = 4.5. An excellent agreement between the experimental distance distribution curve and that calculated from a model consisting of two lobes linked by the Cys(18) Cys(30) disulphide bridge. PMID- 2307141 TI - A note on sequence-dependence of DNA structure. AB - A circular dichroism study was conducted on the solution structure of several different oligonucleotides, whose X-ray structures have been solved. It is suggested that in aqueous solution the oligonucleotides can form structures that maintain geometrical elements which are typical of B-DNA, A-DNA, and their intermediate forms. It is shown that 5'GGATGGGAG:5'CTCCCATCC, which forms an A DNA helix in the crystal state (McCall et al. 1986), in aqueous solution maintains an A-DNA like structure at temperatures below 10 degrees C. At temperatures between 10 degrees C and 25 degrees C it shows a tendency to form an intermediate structure between A-DNA and B-DNA. Also, it is shown that TFE does not cause a transition from B-DNA to A-DNA helix in short DNA fragments, but instead disrupts the helix. PMID- 2307142 TI - Pure and mixed lipid black foam films as models of membrane fusion. AB - Black foam films (BFF) from water solutions of the phospholipid dilauroyl lecithin (DLL) with admixtures of palmitoyl lysolecithin (Lyso) were formed. Microscopic BFF were studied by the method of Scheludko and Exerowa. The formation probability for BFF and the BFF lifetime in a black state before film rupture were measured as functions of the film composition. At a fixed overal lipid concentration it was shown that an increased percentage of Lyso exponentially increased the lifetime of the film up to the CMC of Lyso. This stabilizing Lyso effect nicely corresponds with its stabilizing action on the waiting time for fusion of two contacting black lipid membranes (BLM), as found by Chernomordik et al. In contrast, Lyso is known to destabilize a single BLM. In this way we have found experimental proof of our earlier prediction that Lyso should have opposite effects on the lifetimes of BLM and BFF. In addition, we have shown for the first time that foam films made of lipids are a convenient model for monolayer membrane fusion studies. This model is characterized by its simplicity and experimental reliability and provides a means for quick screening of the fusogenic capacity of various amphiphilic and hydrophilic admixtures. PMID- 2307143 TI - Binding of Cu(II), Tb(III) and Fe(III) to chicken ovotransferrin. A kinetic study. AB - The kinetics of binding of Cu(II), Tb(III) and Fe(III) to ovotransferrin have been investigated using the stopped-flow technique. Rate constants for the second order reaction, k+, were determined by monitoring the absorbance change upon formation of the metal-transferrin complex in time range of milliseconds to seconds. The N and C sites appeared to bind a particular metal ion with the same rate; thus, average formation rate constants k+ (average) were 2.4 x 10(4) M-1 s 1 and 8.3 x 10(4) M-1 s-1 for Cu(II) and Tb(III) respectively. Site preference (N site for Cu(II) and C site for Tb(III] is then mainly due to the difference in dissociation rate constant for the metals. Fe(III) binding from Fe nitrilotriacetate complex to apo-ovotransferrin was found to be more rapid, giving an average formation rate constant k+ (average) of 5 x 10(5) M-1 s-1, which was followed by a slow increase in absorbance at 465 nm. This slow process has an apparent rate constant in the range 3 s-1 to 0.5 s-1, depending upon the degree of Fe(III) saturation. The variation in the rate of the second phase is thought to reflect the difference in the rate of a conformational change for monoferric and diferric ovotransferrins. Monoferric ovotransferrin changes its conformation more rapidly (3.4 s-1) than diferric ovotransferrin (0.52 s-1). A further absorbance decrease was observed over a period of several minutes; this could be assigned to release of NTA from the complex, as suggested by Honda et al. (1980). PMID- 2307145 TI - Symposium on Health Effects of Occupational Exposure to Inorganic Dusts. Maastricht, The Netherlands, March 1989. Proceedings. PMID- 2307144 TI - Time-resolved fluorescence studies of flavodoxin. Fluorescence decay and fluorescence anisotropy decay of tryptophan in Desulfovibrio flavodoxins. AB - The time-resolved fluorescence characteristics of tryptophan in flavodoxin isolated from the sulfate-reducing bacteria Desulfovibrio vulgaris and Desulfovibrio gigas have been examined. By comparing the results of protein preparations of normal and FMN-depleted flavodoxin, radiationless energy transfer from tryptophan to FMN has been demonstrated. Since the crystal structure of the D. vulgaris flavodoxin is known, transfer rate constants from the two excited states 1La and 1Lb can be calculated for both tryptophan residues (Trp 60 and Trp 140). Residue Trp 60, which is very close to the flavin, transfers energy very rapidly to FMN, whereas the rate of energy transfer from the remote Trp 140 to FMN is much smaller. Both tryptophan residues have the indole rings oriented in such a way that transfer will preferentially take place from the 1La excited state. The fluorescence decay of all protein preparations turned out to be complex, the parameter values being dependent on the emission wavelength. Several decay curves were analyzed globally using a model in which tryptophan is involved in some nanosecond relaxation process. A relaxation time of about 2 ns was found for both D. gigas apo- and holo-flavodoxin. The fluorescence anisotropy decay of both Desulfovibrio FMN-depleted flavodoxins is exponential, whereas that of the two holoproteins is clearly non-exponential. The anisotropy decay was analyzed using the same model as that applied for fluorescence decay. The tryptophan residues turned out to be immobilized in the protein. A time constant of a few nanoseconds results from energy transfer from tryptophan to flavin, at least for D. gigas flavodoxin. The single tryptophan residue in D. gigas flavodoxin occupies a position in the polypeptide chain remote from the flavin prosthetic group. Because of the close resemblance of steady-state and time-resolved fluorescence properties of tryptophan in both flavodoxins, the center to center distance between tryptophan and FMN in D. gigas flavodoxin is probably very similar to the distance between Trp 140 and FMN in D. vulgaris flavodoxin (i.e. 20 A). PMID- 2307146 TI - Epidemiologic studies of inorganic dust-related lung diseases in The Netherlands. AB - The results of two epidemiologic investigations on dust-related lung diseases are presented. The two studies had different aims and designs. A cross-sectional study was done to investigate the silicosis prevalence in Dutch fine ceramic workers. In the small ceramic workshops in the Gouda region, simple pneumoconiosis is still commonly present (13.3%), whereas the silicosis prevalence in the highly mechanized industries is low (1.7%). Furthermore, heavy smoking seems to enhance the risk for silicosis after long-term exposure to quartz. A case-control study was performed to analyze the relation between dust exposure in the fine ceramic and coal mining industries and lung cancer. No relation between a work history in the dusty trades and lung cancer emerged, and a correlation with a specific histologic tumor cell type could not be demonstrated. Apparently, workers in the Dutch fine ceramic or coal mining industry have no increased risk of developing lung malignancies. PMID- 2307147 TI - Total respiratory impedance measurement by forced oscillations: a noninvasive method to assess bronchial response in occupational medicine. AB - The forced oscillation technique is a noninvasive and effort-independent test to characterize the mechanical impedance of the respiratory system. By applying a complex signal, the frequency-dependent behavior of the respiratory system can be measured over an extended spectrum. For clinical practice, the input impedance is used most frequently; pressure and flow are measured at the same place. The impedance can be partitioned into a real part or resistance and an imaginary part or reactance. At low frequencies, reactance is determined by the capacitance of the system and at high frequencies by the inertial properties of the system. Equipment and impedance data in normal subjects and patients with chronic obstructive pulmonary disease are discussed. The frequency-dependent behavior of the respiratory system is described with the use of an electrical model characterized by partitioning of airway resistance and the presence of shunt compliance represented by the compliance of the intrathoracic airway walls. Influences of peripheral resistance, airway compliance, lung volumes, chest wall and pulmonary resistance, and resistance of the cheeks and upper airways are analyzed. Input impedance can be applied to the detection of bronchoconstriction and bronchodilation, but this technique is suitable for detecting early airway abnormalities caused by smoking or occupational hazards. PMID- 2307148 TI - Molecular epidemiology of coal worker's pneumoconiosis: application to risk assessment of oxidant and monokine generation by mineral dusts. AB - It is generally accepted that fibrotic lung diseases are mediated by macrophage derived cytokines and growth factors. Basic research continues to find new factors involved in these disease processes to incorporate into new hypotheses. Two hypotheses implicitly generated by recent findings were tested in an epidemiologic approach among workers in coal mines. This approach is described as molecular epidemiology and is exemplified by two studies focused on different mechanistic aspects of coal workers' pneumoconiosis (CWP): antioxidants in red blood cells of miners with CWP and generation of tumor necrosis factor (TNF) by blood monocytes of miners with CWP. Most findings in the antioxidant study may merely be reflections of pulmonary inflammatory processes. Some data in the TNF study indicate, however, that TNF release is a risk factor for the development of lung fibrosis after prolonged exposure to coal mine dust. PMID- 2307150 TI - Aspects of chromosome preparation. PMID- 2307149 TI - Abnormal secretion of interleukin-1 and tumor necrosis factor alpha by alveolar macrophages in coal worker's pneumoconiosis: comparison between simple pneumoconiosis and progressive massive fibrosis. AB - The aim of this study was to compare the secretion of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by alveolar macrophages (AMs) harvested from patients with coal worker's pneumoconiosis (CWP) and control subjects. We observed higher levels of spontaneous TNF alpha and IL-1 secretion by AMs from patients with CWP than in those from healthy controls. We did not find any significant difference between the two groups in the incidence of simple pneumoconiosis and progressive massive fibrosis. In the group of coal miners without radiologic signs of pneumoconiosis, we found high levels of both cytokines in a subgroup of subjects still exposed to the mineral dust but not in the subgroup of subjects removed from exposure. These results indicate that AMs are involved in chronic lung inflammatory reactions to mineral dusts, partly by way of cytokine secretion. Moreover, cytokine secretion by AMs appears to be an early event that is detectable at the moment of mineral dust exposure. The results open new perspectives in the study of the mechanisms leading to CWP. PMID- 2307151 TI - Sodium fluoride is a less efficient human cell mutagen at low concentrations. AB - Sodium fluoride was found to induce gene-locus mutations at the thymidine kinase (tk) and hypoxanthine guanine phosphoribosyl transferase (hgprt) loci in human lymphoblastoid cells. A single, 28 hr exposure to up to 600 micrograms/ml sodium fluoride induced a concentration-dependent increase in mutant fraction at both gene loci and reduced cell survival to 12% relative to negative control cultures. When cells were exposed to sodium fluoride concentrations that were only minimally toxic using a 20 day treatment protocol, no detectable induction of mutation was ob-served at the hgprt locus, and induction of mutation was observed at the tk locus only for treatment with 65 micrograms/ml sodium fluoride; exposure to 50 and 35 micrograms/ml sodium fluoride did not induce detectable mutation. The assay protocol used was of sufficient statistical sensitivity to detect the level of mutation predicted based on a linear extrapolation of data obtained from a 28 hour exposure. The implications of these observations with regard to the extrapolability of mutagenicity data to low concentrations are discussed. PMID- 2307152 TI - Genotoxic effects of five polycyclic aromatic hydrocarbons in human and rat mammary epithelial cells. AB - Five polycyclic aromatic hydrocarbons (PAHs) of different carcinogenic activities were evaluated for their effects on DNA synthesis (3HTdR labeling index (L.I.] of rat and human mammary epithelial cells (MEC) and for their effects on chromosomes in MEC-mediated sister chromatid exchange (SCE) assays. When compared with DMSO treated cells, exposures of rat MEC to the two most potent carcinogens (5 micrograms/ml for 24 hr), i.e., 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (B[a]P), resulted in a 45-62% reduction in the L.I. of rat MEC. Another carcinogen, 20-methylcholanthrene (MCA), produced a 35-48% reduction in L.I., while the noncarcinogenic PAHs, 1,2-benzanthracene (BA) and benzo(e)pyrene (B[e]P), showed no effect. Similarly, exposures of human MEC to DMBA and B[a]P resulted in a 50-90% depression in L.I. while BA was significantly less effective (30% reduction). When co-cultivated with Chinese hamster V-79 cells in the presence of PAH, both rat and human MEC can activate and release the active metabolites to induce SCE in V-79 cells. In the rat MEC-mediated assay for all 5 PAHs, the frequencies of SCE per chromosome in DMBA-, B[a]P-, MCA-, BA-, B[e]P-, and DMSO (solvent control)-treated groups were 6, 3, 1.4, 0.7, 0.4, and 0.3, respectively. DMBA was most effective in increasing SCE, while B[e]P was ineffective. In the human MEC-mediated assay, B[a]P was more effective than DMBA in inducing SCE, and the frequencies of SCE per chromosome were 4.5 and 3.6 in B[a]P- and DMBA-treated groups, respectively. Comparing depression of L.I., SCE, and in vivo carcinogenicity for the 5 PAHs, SCE mediated by rat MEC is better correlated with carcinogenicity in rat than L.I. depression. PMID- 2307153 TI - Nutritional status of young adult Ethiopians before onset and after treatment of diabetes mellitus. AB - Young diabetics in tropical countries are often undernourished, insulin-requiring and ketosis-resistant, and are sometimes considered to have a distinct type of diabetes. Therefore, a survey of young adult diabetics attending Yekatit 12 Hospital, Addis Ababa, was made to determine clinical features and the relation between their diabetes and their nutritional state. In May, 1988, 894 of 1490 registered diabetic patients were attending regularly, of whom 248 became diabetic between the ages of 15 and 35 years. Many had been followed for 6 years or more. Of the 248,69 males and 29 females (39.5%) had body mass index (BMI) of less than 18 kg/m2 at diagnosis of diabetes. However, only 3.5% of the 199 who knew their pre-diabetic weight had been less than 18 kg/m2; 13.8% of males and 48.5% of females had been obese. At their last attendance, 50% of those whose BMI at diagnosis was less than 18 were of normal weight and only 13% had gained no weight. Of the 98 with BMI less than 18 at diagnosis, and the further 18 less than 18 kg/m2 by the time insulin was started, ketosis occurred at some time in 22%. Only 1 patient takes more than 1.5 units of insulin per kg per day, and 30% of those needing 1.0 to 1.5 U/kg have had tuberculosis. Only 15 of the 116 patients who had BMI less than 18 failed to gain weight on treatment. It is concluded that, in most, the malnutrition at presentation was due to the diabetic state and did not precede the diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307154 TI - Analysis of surgical admissions to the Ethio-Swedish Children's Hospital (1984 1988) in Addis Ababa. AB - Surgical problems in children result in significant morbidity and mortality. A retrospective analysis of all surgical patients admitted to the Ethio-Swedish Children's Hospital (ESCH) over a five year period from 1984 to 1988 was made. There were a total of 2,281 surgical patients admitted, accounting for 22% of all hospital admissions (total = 10,364). The gastrointestinal and musculoskeletal systems were the most common systems involved. Acute appendicitis accounted for 13.9% (N = 318), cleft-lip and palate 8% (N = 183), and burns 6.9% (N = 157) of all surgical admissions. Accidents and trauma accounted for 25% of the surgical admissions (N = 564). Of these, the most common conditions were burns, car accidents, accidental falls, and foreign body aspirations. The over all mortality rate was 4% (N = 98). Acute appendicitis, intussusception, acute laryngotracheobronchitis (ALTB), and burns were associated with a high mortality. Of the neonatal admissions, one third died shortly after surgery, probably due to anaesthetic, fluid and electrolyte imbalance. Examination of the general pattern of surgical admissions revealed that many of the conditions were preventable, or amenable to medical therapy if detected early. Health education of the public is therefore necessary in order to reduce the morbidity and mortality of these conditions. PMID- 2307155 TI - Plasma level distribution, effect and toxicity of antiepileptic drugs among Ethiopian epileptics. AB - Plasma phenytoin and phenobarbitone levels were estimated in 123 adult Ethiopian epileptics by gas-liquid chromatography. Thirty four (38.2%) of the patients on phenytoin, and 52 (52%) of those on phenobarbitone, had plasma levels in the conventional therapeutic ranges of 10-20 micrograms/ml and 10-30 micrograms/ml respectively. Of the 89 patients who were taking phenytoin either singly or combined with phenobarbitone, motor disturbances (ataxia and nystagmus) were seen in 31 (34.8%) and dysmorphic and idiosyncratic side effects including gum hypertrophy, hirsutism, acne and skin rash in 37 (41.6%). Subnormal serum calcium levels were noted in 15 (30.6%) and high alkaline phosphatase was found in 13 (26.5%). Phenobarbitone was found to be an effective anticonvulsant (78.1% seizure control rate), with adverse effects of sedation and intellectual depression. Seizure control was achieved in 77.1% of patients on a single drug as opposed to 55.6% on combination of phenytoin and phenobarbitone (p less than 0.05). The overall seizure control rate was 66%. PMID- 2307156 TI - Leukaemia in adult Ethiopians. AB - The pattern of leukaemias in adult Ethiopians admitted to Tikur Anbessa (Black Lion) Hospital, a teaching and referral hospital in Addis Ababa, Ethiopia, from January 1982 to December 1987 [corrected] is analyzed. There were a total of 7969 medical admissions, of which 180 (2.3%) were for leukaemia. The age range was 14 to 80 years, with a mean of 37.6 years. The male:female ratio was 2.3:1. The commonest type of leukaemia was chronic myeloid leukaemia (CML) 57.8%, acute leukaemias and chronic lymphatic leukaemia (CLL) accounted for 21.1% each. Of the acute leukaemias, 53.3% were lymphoblastic (ALL) while 46.7% were acute myeloblastic (AML). Most patients came from Addis Ababa (30.6%) and Shoa (28.9%) regions. The overall incidence of leukaemia in Addis Ababa population was estimated at 1.95 +/- 0.79/100,000/year at 95% confidence interval. The purpose of this study is to attempt a detailed description of leukaemias in Ethiopian patients and compare the findings with similar studies from other countries. Leukaemias are commoner than previously thought, and warrant further study in the community so that management, especially of acute forms, can be improved. PMID- 2307157 TI - Tuberculous polyp in the middle ear of an infant. AB - A five-month old infant presented with purulent discharge from the right middle ear. On examination the child had a weight less than 50% of Harvard standard and a polyp in the right middle ear. Histological examination of the polyp showed tuberculosis. Tuberculous polyp of the middle ear is presented and discussed. PMID- 2307158 TI - Actinomycosis of the ear. AB - A case of primary actinomycosis of the ear in a 15 year old Ethiopian girl is described and discussed. PMID- 2307159 TI - The association of serum proteins with preeclampsia. AB - In 239 pregnant women, 107 with preeclampsia and 132 controls, phenotype frequency distribution of serum group-specific component (Gc) and haptoglobin (Hp) was studied by disc-electrophoresis in polyacrylamide gel. The results demonstrate a significant statistical difference in phenotype frequency distribution of the Gc-system. Gc 2-1 phenotype was expressed significantly in women with preeclampsia compared to controls. Gc 2-1 phenotype may be useful as a genetic marker for early detection of preeclampsia. PMID- 2307160 TI - The effect of habitual sustained endurance exercise on cardiac structure and function. AB - We performed echocardiographic evaluation of 20 male veteran endurance runners (mean age 56 +/- 7 years) and compared them with a group of age-matched controls. All the runners had run at least 25 miles per week for more than 25 years. Although only four athletes showed voltage ECG evidence of left ventricular hypertrophy, using echocardiography, 10 athletes had evidence of left ventricular hypertrophy. Thus electrocardiography is insufficiently sensitive to detect LVH in this group (10%). Left ventricular posterior wall thickness and left ventricular mass were significantly greater in the athletes, the difference becoming more marked when LV mass was corrected for body surface area and, consequently, the wall thickness: cavity diameter ratio was increased (P less than 0.04). There was no difference between the two groups in left ventricular performance and no correlation between left ventricular mass and running ability. Thus, veteran runners develop structural cardiac changes similar to younger power trained athletes and do not show characteristics normally expected of 'volume overload' which is thought to occur in running. PMID- 2307161 TI - Relative survival of patients after heart valve replacement. AB - Long-term results after prosthetic heart valve replacement are usually presented in actuarial terms, which do not take into account the background mortality of the general population. The calculations of the relative survival, which is the ratio between the observed survival in a group of patients during a specified time interval and the survival expected from the general population experience, permit correction for important demographic variables. We have analysed the long term relative survival rates in a consecutive series of 841 Norwegian patients who, on the basis of clinical symptoms, underwent aortic (AVR, n = 617), mitral (MVR, n = 146), and double (AVR + MVR, n = 78) valve replacement between June 1977 and January 1985. The follow-up was closed on May 1st 1986, was 100% complete and included 2056 patient-years. The actuarial survival data for the total cohort was 75.1%, and for AVR, MVR and DVR, 77.9, 69.7 and 63.0%, respectively. The corresponding figures for the relative survival were 83.5, 87.0, 76.6 and 69.1%, respectively. Within the subgroup undergoing AVR, our analysis demonstrated a poor prognosis in those who were operated for pure aortic regurgitation or endocarditis, as well as in those who received the smallest valve size prosthesis due to a narrow aortic root. In this analysis, as in the analysis of the total material, we observed that the differences between survival in the patients and in the general population were of smaller magnitude when based on relative survival rates than when analysed in the standard (actuarial) way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307162 TI - The results of surgery for atrial septal defect in patients aged fifty years and over. AB - We examined the cases of 31 patients over the age of 50 years undergoing operative closure of isolated ostium secundum atrial septal defect. The lesion had been diagnosed in all cases prior to cardiac catheterization. To assess the importance of pre-operative data on surgical outcome, the patients were first divided into three groups according to mean pulmonary artery pressure (PAP): less than 16 mmHg (Group A), 16-30 mmHg (Group B) and greater than 30 mmHg (Group C). Symptomatic improvement occurred in all groups but more patients in Group C, although symptomatically improved, remained short of breath and in atrial fibrillation than in Group A. Patients in Group A had a higher actual forced vital capacity expressed as a percentage of the predicted value (FVCa/FVCp) than patients in Group B or Group C (P less than 0.015). There was a good correlation between FVCa/FVCp and percentage oxygen saturation of the arterial blood (P less than 0.0009). This simple non-invasive investigation was therefore found to correlate with previously documented parameters, pulmonary artery pressure and percentage oxygen saturation of the arterial blood, affecting surgical outcome. Patients were also divided into groups according to FVCa/FVCp: less than 75% (Group 1), 50-75% (Group 2) and less than 50% (Group 3). Postoperative symptoms were more common in Group 3 than in Group 1. We conclude that respiratory function tests, as well as measurement of pulmonary artery pressures, are useful in predicting improvement following atrial septal repair. PMID- 2307163 TI - Early appearance of left ventricular thrombi after anterior myocardial infarction: a marker of higher in-hospital mortality in patients not treated with antithrombotic drugs. AB - Left ventricular thrombus may develop both early and late after acute anterior myocardial infarction. To assess the possible prognostic implication of the time of thrombus appearance, 125 patients (87 males; age ranging from 35 to 92 years, mean: 65 +/- 10 years) consecutively admitted to our coronary care unit within 24 h of a first acute anterior myocardial infarction, untreated with antithrombotic drugs, underwent serial two-dimensional echocardiographic studies during hospitalization, then monthly for a follow-up of 1-48 (mean: 23 +/- 16) months among survivors. Left ventricular thrombi, detected in 71 patients (57%), appeared from 1 to 362 (mean: 13 +/- 44) days after acute infarction. In 40 patients (56%), early thrombus development, within 48 h of symptom onset, was noted. During the study period, 52 patients (42%) died. Global mortality rate was similar in patients with thrombi compared with those without thrombi (32/71: 45%, vs 20/54: 37%; P = ns). However, in-hospital mortality of patients who developed left ventricular thrombi within 48 h (17/40: 42.5%) was significantly higher compared with both patients with later thrombus appearance (4/31: 13%; P less than 0.008) and those without thrombi (10/54: 20%; P less than 0.01). Embolic events were more frequent in patients with thrombi (9/71, 13% vs 1/54, 2%; P less than 0.02), but there was no relationship with the time of thrombus appearance. The values of peak CPK levels and the degree of left ventricular wall motion abnormalities observed in patients with early left ventricular thrombus were significantly higher than the values detected in patients without thrombi, but similar to those obtained in patients with later thrombus occurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307164 TI - New bundle branch block after coronary artery bypass grafting--evaluation by CK MB isoenzyme analysis and transoesophageal echocardiography. AB - Twelve patients with a new complete bundle branch block after coronary artery bypass grafting underwent transoesophageal echocardiography (TEE). The results of TEE were compared with the pre-operative ventriculography, CK-MB isoenzyme time release curves and clinical course. In eight patients with transient right bundle branch block or bifascicular block, low CK-MB activities and an uncomplicated postoperative course, transoesophageal echocardiography showed no new segmental wall motion abnormalities apart from a paradoxical septal movement in five. A persistent right or left bundle branch block was associated with either elevated isoenzyme activities, transoesophageal echocardiographic evidence of new segmental wall motion disturbance or both in four patients. One patient died because of fatal arrhythmia and one suffered from a prolonged low cardiac output syndrome. A transient bundle branch block is usually a benign electrocardiographic finding. In case of a persistent bundle branch block associated with elevated CK MB isoenzymes, new left ventricular wall motion disturbances indicating a peri-operative myocardial injury are easily detected by transoesophageal echocardiography. PMID- 2307165 TI - Inheritance of heart structure and physical exercise capacity: a study of left ventricular structure and exercise capacity in 7-year-old twins. AB - The maximal aerobic power of endurance athletes is high and their heart is characterized by a larger left ventricular internal dimension than in non athletes, and a proportional increase of wall thickness; these traits may be inherited and/or the consequence of intense physical training. To assess the influence of inheritance on physical exercise capacity and on echocardiographically determined cardiac structure, and to limit the effect of environmental factors as much as possible, we studied 15 monozygotic and 19 dizygotic 6- to 8-year-old twin pairs. Exercise capacity was expressed as the times at which the heart rates of, respectively, 150 and 170 beats min-1 were reached during a progressive exercise test on the treadmill. For these exercise times the within-pair variance was significantly larger in dizygotic compared with monozygotic twins. Therefore significant genetic variance was inferred, both when the exercise times were expressed as absolute values and after adjustment for body weight and gender. As for cardiac structure at rest, the results did not suggest a significant influence of genetic endowment on left ventricular internal diameter or on wall thickness; genetic variance was significant, however, for calculated left ventricular mass (P less than 0.05) and left ventricular mass adjusted for body weight and gender. The results are compatible with the notion that the high aerobic power of endurance athletes is at least partly inherited. Left ventricular internal dimension and wall thickness, which distinguish an athlete's heart at rest from the heart of a non-athlete, do not show a significant genetic component, suggesting that the qualities characteristic of an athlete's heart, at least as assessed at rest, are not inherited. The inheritance of aerobic power may be due to inheritance of non-cardiac factors or to cardiac features which are only expressed during exercise. PMID- 2307166 TI - Transcatheter ablation of the sinus node in dogs using high-frequency current. AB - Sinus node ablation by high-frequency current (HFC) (0.7 MHz. 5-10 W), delivered through the distal electrode of a conventional endocavitary catheter, was induced in seven thoracotomized dogs under autonomic blockade. The HFC was delivered for variable periods of time under ECG monitoring, while sinus tachycardia was produced or after attaining sinus arrest. The procedure was repeated until a stable non-sinus rhythm was obtained. Sinus rhythm was abolished in all seven dogs after a variable number (7-20) of discharges. The escape rhythm obtained after the last discharge, characterized by means of epicardial electrodes and analysis of P-wave morphology, length of PR interval and the rate, showed an atrial activation pattern different from sinus rhythm in all cases. The P-wave was retrograde in two cases, and in one case no atrial activity was detected after the last discharge; however, atrial activity recovered after 35 min, the activation pattern being different from the controls. After 2 h, sinus rhythm had not returned in any case. In no case was there perforation of the atrial wall. Acute histological findings showed coagulation necrosis of the endocardium, extending to the muscle fibres and affecting the sinus cells. PMID- 2307167 TI - Calcific aortic stenosis in twins: a clue to its pathogenesis? AB - A pair of identical twins presented almost simultaneously at age 62 years with calcific aortic stenosis requiring surgery, one with bicuspid and one with tricuspid aortic valve. This suggests that bicuspid morphology may perhaps not be the cause, but may be a genetically linked marker of an inherited predisposition to calcific stenosis. PMID- 2307168 TI - Technically suboptimal first-pass radionuclide angiographic studies. AB - First-pass radionuclide angiography (FPRNA) has proven to correctly assess left ventricular function, however, technical difficulties do occur. One hundred and thirty one patients had contrast angiography and resting radionuclide angiography within 24 h. Of the 131 patients, 86 (66%) had adequate studies and 45 (34%) were technically suboptimal studies. In the latter group, low counts affected the quality of the images but did not change the left ventricular ejection fraction (LVEF) or regional wall motion (RWM) scores. Patients with high background activity showed overestimation of LVEF, however, by using a formula that was derived from the linear regression the LVEF could be calculated accurately in most cases. Multiple technical problems were noted in 14 patients in whom the best correlation was between contrast LVEF and background uncorrected LVEF from FPRNA (r = 0.87). In the latter group, FPRNA showed overestimation of RWM in 8 patients (57%), mainly in the inferior wall. We conclude that for most technically compromised first-pass radionuclide angiographic data, accurate LVEF values can be achieved but errors in regional wall motion interpretation will occur, especially when multiple technical problems exist. PMID- 2307170 TI - External quality control of gamma cameras--results of an inter-laboratory comparison study in Austria. AB - Some 28 nuclear medicine departments out of a total of 40 participated in a nationwide Austrian interlaboratory comparison of the imaging quality of gamma cameras. The participation was voluntary, and confidentiality of the individual results was guaranteed. The survey was completed within 2 months, employing instructors to administrate the tests. An emission phantom simulating a flood field with non-uniformities was imaged by 43 cameras, and 54 images were evaluated. The test images were read by the participants using a graded rating scale to indicate the probability of the presence of a non-uniformity in the various parts of the image. The rating data were used to construct individual ROC curves for each image. The area under the ROC curve was used as the ranking parameter for image quality. The results show a spread of the ROC areas between 0.6 and 0.99, with a median of 0.81. A correlation was found between the year of installation and the ROC area obtained from the gamma camera, indicating improvements of performance in more recent cameras, which accounts for part of the variation of the ROC areas. The remaining variations are due to differences in the performance of the gamma cameras. Feedback was provided to the participants by describing individual performance with respect to the true structure of the phantom and by comparing this performance with that of the group. A questionnaire accompanying the test phantom yielded information about the practice of routine quality control and about details of the acquisition and analysis of images.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307169 TI - "Luxury perfusion" with 99mTc-HMPAO and 123I-IMP SPECT imaging during the subacute phase of stroke. AB - To compare the merits of 123I-isopropyl-iodoamphetamine (123I-IMP) and 99mTc HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with 123I-IMP and 99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal 99mTc-HMPAO SPECT and abnormal 123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on 99mTc-HMPAO in areas corresponding to defects on the 123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination, 99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on 123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with 99mTc-HMPAO and was absent for both 123I IMP and 99mTc-HMPAO in 3. We suggest that SPECT with 99mTc-HMPAO could show transient hyperemia not demonstrated by 123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with 99mTc-HMPAO than with 123I IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism. PMID- 2307171 TI - Methoxyisobutylisonitrile (MIBI) Tc 99m SPECT to establish a correlate to coronary flow reserve, the perfusion reserve, from global and regional myocardial uptake after exercise and rest. AB - With 99mTc-MIBI SPECT and a 4 h exercise (E: 150 MBq iv) and rest (R; 800 MBq iv) protocol, global and regional left ventricular (LV) myocardial uptake was determined in 70 patients with angiographically confirmed coronary heart disease (CHD) and in 10 controls. The aim was to establish an E/R ratio as a correlate to coronary vascular reserve, representing perfusion reserve (PR). E/R ratios, obtained from total LV myocardium or from normal or impaired regions, were greater than 1.19 under all conditions, indicating the presence of higher flow during exercise than at rest (even in areas of low flow). Global PR separated (P less than 0.01) controls (1.63 +/- 0.21; mean +/- SD) from severely diseased patients (1.29 +/- 0.14 in 2- or 3-vessel disease) only. Improved differential diagnosis was gained from calibrating the regional E/R ratio to regional differences (E minus R) of uptake. For the left ventricle regional PRs (RPR) for 25 ROIs of the target, framing the myocardium, were determined. RPR at the regional maximum of 99mTc-MIBI uptake was similar in both controls (1.66) and patients (1.63), indicating a high probability of meeting some areas with functionally normal perfusion in patients with CHD. RPR allowed sufficient separation (P less than 0.025) concerning the degree of coronary artery stenosis (RPR in occlusion, 0.26; stenosis greater than 75%, 0.39; less than 75%, 0.56). In controls, the overall value for RPR was 1.14 +/- 0.28 (P less than 0.001). LV global PR and RPR were useful in separating patients with CHD vs controls and in classifying the severity of vascular stenosis. PMID- 2307172 TI - Low levels of serum thyroglobulin after withdrawal of thyroid suppression therapy in the follow up of differentiated thyroid carcinoma. AB - We evaluated the reliability of very low serum thyroglobulin (Tg) levels (less than 3 ng/ml) obtained after withdrawal of thyroid suppression therapy in 224 patients without anti-Tg antibodies, who had undergone total thyroidectomy (125 patients) or thyroidectomy followed by 1 or more courses of 131I therapy (99 patients), by performing whole body scans after a therapeutic course of 131I given at the same time of Tg measurement. In 79 patients (35%) a positive scan, associated with a very low level of Tg, was noted. The 131I uptake was limited to the thyroid bed in 60 patients, but metastases were demonstrated in 19 patients (8.5%). These results are mainly explained by the much improved performance of scintigraphy after administration of therapeutic doses of 131I. In the majority of patients, especially those whose 131I uptake was limited to the thyroid bed, further scans were negative. Therefore, in these cases, negative Tg values can generally be considered an early indication of satisfactory evolution. However, in 8.5% of all cases, very low Tg levels were associated with metastases. Thus the follow up of thyroid cancer should not rely only upon Tg determination, even after suppression therapy withdrawal. PMID- 2307174 TI - Annual meeting of the Deutsche Gesellschaft fur Zellbiologie. Bremen, 19-23 March 1990. Abstracts. PMID- 2307173 TI - On an alternative method of estimating effective dose equivalent. PMID- 2307175 TI - Complement regulation on the surface of cultured schistosomula and adult worms of Schistosoma mansoni. AB - Cercaria and freshly prepared schistosomula of Schistosoma mansoni are highly sensitive to complement. However, early in their maturation, the schistosomula become resistant to complement killing. This conversion is preceded by a rapid and massive release of several acetabular proteases and of the glycocalyx coat. Thus, shedding of the glycocalyx which is a major immunogen and a strong activator of the alternative pathway of complement permits the parasite to escape immune damage. Mechanically transformed schistosomula, which were cultured in a defined synthetic medium and developed complement resistance, could be converted by proteolysis to complement sensitivity. Trypsin and pronase markedly increased the susceptibility of cultured schistosomula to complement. The trypsin-induced complement sensitivity persisted for at least 19 h without recovery of resistance. Similar treatment with trypsin produced complete killing of adult worms by complement in absence of antibodies. Efficient killing was obtained with normal human serum (NHS), with normal guinea pig serum (GpS), and with C4 depleted HS and C4-deficient GpS indicating that the killing was mediated by the cytolytic alternative pathway of complement. Larger quantities of C3b with intact alpha' chain could be demonstrated on trypsin-treated than on non-treated schistosomula. Antibodies which were raised in rabbits by immunization with the trypsin-released material bound to cultured (non-treated) schistosomula and to adult worms, and induced their killing in GpS and C4-deficient GpS. These results suggest that following release of the glycocalyx, the transforming schistosomula of S. mansoni spontaneously express a complement regulatory protein(s). A similar regulator is postulated to be present on the surface of adult worms. Such regulatory molecules may serve as good targets for immunotherapy, since antibodies directed to them will inhibit their regulatory activity and thus potentiate in vivo the lytic action of complement. PMID- 2307176 TI - Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis. AB - Interleukin 6 (IL6) is one of the major inflammation-associated cytokines. Elevated serum or tissue levels of IL6 have been reported to occur in several human diseases, including infections of the central nervous system (CNS), but not in non-infectious CNS inflammation, e.g. multiple sclerosis. While studying experimental autoimmune encephalomyelitis (EAE) as an animal model for autoimmune inflammation of the CNS, we found increased IL6 levels in the CNS of mice suffering from a lethal form of the disease. IL6 levels in the spleens and sera were not significantly increased. These findings are indicative of local production of IL6 in the CNS during EAE, and represent the first demonstration of IL6 production in non-infectious CNS inflammatory disease. PMID- 2307177 TI - Glucocorticoid hormones reduce the expression of major histocompatibility class I antigens on human epithelial cells. AB - Expression of a critical level of major histocompatibility complex (MHC) class I antigens on epithelial cells is a prerequisite for the action of specific cytolytic immune response cells. Glucocorticoid hormones have strong immunosuppressive effects. Therefore, we investigated the influence of the synthetic glucocorticoid dexamethasone on the expression level of MHC class I antigens on human epithelial cell lines. Long-term treatment with dexamethasone leads to reduced MHC class I surface antigen expression and to decreased total membrane-bound MHC class I protein. The steady-state mRNA level is significantly decreased and the transcription rate of MHC class I genes is reduced. PMID- 2307178 TI - Immigration of thoracic duct B lymphocytes into established germinal centers in the rat. AB - Immigration of B lymphocytes into established germinal centers in the rat was studied by transferring genetically marked thoracic duct B cells to non irradiated congenic hosts at various times between 3 days before and 6 days after host immunization. Seven days after host immunization, the distribution of donor B cells to lymph node germinal centers (relative to their distribution to non germinal center lymph node areas) was measured by two-color flow cytometry in which (a) donor and host B cells were distinguished by their Ig kappa chain allotypes, and (b) germinal center B cells were distinguished by their lack of labeling with the monoclonal antibody HIS22. Thoracic duct B cells from long-term antigen-primed rats were found to immigrate into host germinal centers much better than B cells from unprimed donors. This effect was antigen specific: primed B cells only immigrated well into host germinal centers induced by the priming antigen. Although B cells localized in germinal centers most efficiently when injected before immunization, specifically primed donor B cells injected after immunization were still found to be at least as evenly distributed to germinal centers as to other lymph node areas, whereas unprimed B cells transferred after immunization localized poorly in host germinal centers. These findings are discussed in light of recent suggestions that memory B cell clones are maintained by continued antigenic stimulation within secondary lymphoid follicles. PMID- 2307179 TI - R 56865 and flunarizine displace Ca2+ from phosphatidylserine monolayers in a stoichiometric manner. AB - The monovalent cationic drugs, R 56865 and flunarizine added to the subphase, displaced Ca2+ from phosphatidylserine (PS) monolayers at pH 5 with EC50 values of 1.2 X 10(-6) and 1.3 X 10(-6) mol/l. The EC50 of flunarizine for the increase in surface pressure due to incorporation of the drug into the PS film was 1.8 X 10(-6) mol/l. The maximal binding of both drugs to PS monolayers was estimated from experiments in which the drug was added to the spreading solution for the monolayer. The maximal molar binding ratio of R 56865 was identical to twice the maximal Ca2+ binding (2 X 0.13 Ca/PS) to the monolayer. The uptake of [14C]R 56865 into PS monolayers could be measured directly and was well described by a Langmuir isotherm in which the EC50 for 45Ca displacement was taken as the concentration for half-maximal binding, and the molar ratio for twice the Ca2+ binding was taken as maximal molar binding ratio. These results show that two molecules of the univalently charged R 56865 displace one molecule of Ca2+. Maximal binding of the cationic drug flunarizine to PS monolayers showed a similar stoichiometry. 45Ca displacement data may thus be useful for predicting monolayer and perhaps also membrane concentrations of the charged species of cationic drugs. PMID- 2307180 TI - Horizontal transmission of Campylobacter jejuni amongst broiler chicks: experimental studies. AB - Horizontal transmission of Campylobacter jejuni was investigated in campylobacter free broiler chicks. One hundred and twenty chicks housed individually, were provided with water containing 10(2)-10(9) c.f.u./ml C. jejuni. Colonization was rapid [47 of 73 (64%) positive cloacal cultures within 3 days and 65 of 73 (89%) within 7 days], dependent on C. jejuni strain and inoculum size but independent of chick age. Groups of 5-24 chicks in isolators were exposed to C. jejuni contaminated water or colonized seeder chicks. Transmission occurred in 2-7 days concurrent with a gradual increase of C. jejuni in litter, water and feed. Environmental samples were culture-negative within 3 days following removal of colonized chicks. Treatment of 1-day-old chicks with adult caecal microbiota did not affect colonization. Treated and control chicks were all C. jejuni-positive within 3 days of seeder challenge. PMID- 2307181 TI - Prevention of hepatitis B in Italy: lessons from surveillance of type-specific acute viral hepatitis. SEIEVA Collaborating Group. AB - The relative contribution of various risk factors to the incidence of acute hepatitis B in Italy was estimated using a special surveillance system (SEIEVA) for type-specific acute viral hepatitis. At present 146 health departments (USLs) which contain 21% of the Italian population participate in SEIEVA out of the total of 650. Data on 2460 hepatitis B cases and 708 hepatitis A cases were compared. Hospitalization, surgical intervention, dental therapy, other percutaneous exposures, barber shop shaving, i.v. drug abuse and household contact with HBsAg carriers were associated with acute hepatitis B and a large number of cases were attributable to these risk factors. Because the control programme based on vaccination will not be effective in the short term at reducing hepatitis B incidence, other additional interventions are recommended. PMID- 2307182 TI - High incidence of subacute sclerosing panencephalitis in south India. AB - During 1983-7 a clinical diagnosis of subacute sclerosing panencephalitis (SSPE) was confirmed by the detection of measles virus haemagglutination inhibiting antibody in the cerebrospinal fluid (CSF) in 81 subjects resident in Tamilnadu. The antibody titre (reciprocol of the end-point dilution) in the CSF ranged from 2 to 32 and in the sera from 8 to 2048. The CSF:serum ratios of titres were 1:4 1:64 in 80 cases and 1:128 in one case. The median age at onset of SSPE was 10 years and 97% of cases were diagnosed at stage 2 and beyond. Based on the geographic distribution of 72 cases in an estimated population of 8.4 million, the annual incidence of SSPE was calculated to be 2.14 per million population, or 4.3 cases per million children below 20 years. Assuming that only 10% of all cases would have reached the level of laboratory diagnosis, the incidence may be as high as 21 cases per million population. PMID- 2307183 TI - Maintenance of cooling towers following two outbreaks of Legionnaires' disease in a city. AB - This survey assessed the maintenance of evaporative cooling towers in Glasgow, following two Legionnaires' disease outbreaks. Information was obtained from 76 of 81 premises and a maintenance score was calculated for each of 174 towers. The quality of maintenance was extremely varied (range of maintenance scores, 8-30; mean, 22 (S.D., 5.0); median, 23; maximum possible, 33) and some towers were neglected. Breaches of maintenance principles were mainly structural and organizational, e.g. inadequate drift control, rather than failure to use chemicals. Low maintenance scores were associated with no log book, no guidelines, no change in procedures in last 5 years, solitary cooling towers, and towers on industrial premises. Despite intense publicity the standard of cooling tower maintenance in Glasgow remained a concern. Information campaigns directed at those responsible for cooling-tower maintenance are necessary. PMID- 2307185 TI - A prospective study of genital infections in a family-planning clinic. 2. Chlamydia infection--the identification of a high-risk group. AB - During a study of genital infection in inner-city family-planning patients we examined 452 women for Chlamydia trachomatis. The prevalence of infection was 7.3%. There was no significant difference between patients attending because of genital symptoms and those who were attending for routine family-planning advice. Infection was found to be correlated with five main demographic parameters; age less than 25, no stable partnership, hormonal contraception, nulliparity and West Indian Ethnic origin. Using these parameters a simple scoring system was devised which allowed a high-risk population to be defined in whom screening would be economically justified. PMID- 2307184 TI - A prospective study of genital infections in a family-planning clinic. 1. Microbiological findings and their association with vaginal symptoms. AB - A prospective study of genital infection was conducted in four inner-city family planning clinics. Fifteen per cent of routine attenders had symptoms and signs of vaginal infection and many more women attended primarily because of symptoms. Among the women with both signs and symptoms, 70% had positive laboratory findings, Trichomonas vaginalis, Candida albicans and bacterial vaginosis being equally prevalent. Measurement of vaginal pH in the clinic was the single most useful clinical finding for directing empirical therapy. Among patients with a discharge confirmed on examination and an abnormally high pH, 72% had either T. vaginalis or bacterial vaginosis. Neisseria gonorrhoeae was isolated from 4% of women with, and 1% of those without, symptoms. We believe that it is worthwhile to investigate patients presenting to family-planning clinics with vaginal symptoms. No single specimen was found ideal for all pathogens, a cervical swab is better for gonococci and also for T. vaginalis but a vaginal swab is needed for candida and bacterial vaginosis. PMID- 2307186 TI - Experimental observations on the pathogenesis of necrobacillosis. AB - Earlier studies showed that the minimum infective dose (greater than 10(6) organisms) of a virulent strain of Fusobacterium necrophorum could be greatly reduced by suspending the fusobacteria in sub-lethal doses of cultures of other bacteria such as Escherichia coli before inoculating mice subcutaneously. In the present study the infective dose of the same strain of F. necrophorum was reduced by a factor of greater than 10(3) by suspending the fusobacteria in sub-lethal doses of 5% homogenate of gaur or wallaby faeces. Sterile faecal filtrate had no such effect. The sites of low grade infection produced by the prior subcutaneous injection of E. coli culture or gaur faecal suspension were susceptible to superinfection by doses of F. necrophorum far below those required to infect normal tissue. This work helps to explain the production of necrobacillosis by the faecal contamination of small wounds. It proved impossible, however, to produce necrobacillosis in mice by the subcutaneous injection of faecal suspensions from 33 farm cattle. This suggests that the proportion of cattle with virulent F. necrophorum in their faeces is low. PMID- 2307187 TI - Bacterial contamination of weaning foods and drinking water in rural Bangladesh. AB - The aim of this study was to determine what weaning foods and food preparation practices expose children to a high risk of diarrhoeal disease through exposure to a contaminated diet. Bacterial contamination of 897 food and 896 drinking water samples was assessed in a water and sanitation intervention project. The geometric mean of faecal coliforms per g or ml was 7.5 x 10(3) in left-over rice. 1.4 x 10(2) in other types of boiled rice, 2.5 x 10(2) in milk, 4.8 in household drinking water, and 3.5 in bread. Multiplication of faecal coliforms occurred when there was a delay of more than 4 h between preparation and consumption of food. All samples were more contaminated in the rainy than in the dry season. Strategies to reduce contamination should therefore focus on 'wet' foods, early consumption after preparation, and re-heating of left-over foods. Understanding the reasons for the faulty practices is also essential to the formulation of effective measures. PMID- 2307188 TI - Evidence of melanogenesis in porcine retinal pigment epithelial cells in vitro. AB - Several weeks after porcine retinal pigment epithelial (RPE) cell cultures attain confluence, macroscopically visible brown foci appear. The cuboidal cells that form the foci contain numerous phase dark granules that do not exhibit the autofluorescence characteristic of lipofuscin. The data described here indicate that the granules are melanosomes. Electron microscopy revealed three types of electron-dense granules in these cells: simple spheres 0.3-0.5 microns in diameter, large spheres 1-2 microns in diameter, and lysosomal aggregations of the smaller spheres. The matrix of both spheres is composed of 40-nm microvesicles that were also found free in the cytoplasm and aggregated within vacuolar structures. Reversed-phase high-performance liquid chromatography of RPE cells and their media detected melanogens, i.e. intermediates of melanin biosynthesis, including several indole derivatives. The porcine RPE cultures therefore may be a useful system for studying melanogenic regulation. PMID- 2307189 TI - Aqueous humor of cat contains fibroblast growth factor and transferrin similar to those in man. PMID- 2307190 TI - Cytolysis of corneal epithelial cells by hydrogen peroxide. AB - Superoxide radicals or products generated by these radicals in a xanthine/xanthine oxidase system lyse cultured rat and human corneal epithelial cells as measured in a chromium-51 release assay. Partial protection from this lysis is afforded by superoxide dismutase and complete protection is obtained with catalase. Hydrogen peroxide, a product of the dismutation of superoxide radicals, lyses these cells directly and is implicated as the toxic agent in the xanthine/xanthine oxidase reaction. Hydrogen peroxide also decreases cell proliferation and decreases the intact DNA. Therefore, hydrogen peroxide appears to be toxic to corneal epithelial cells. The implications of these data on the safety of hydrogen peroxide as a contact lens disinfectant are discussed. PMID- 2307191 TI - Alpha crystallin from human cataractous vs. normal lenses: change in binding to lens membrane. PMID- 2307192 TI - Glutathione levels in human lens: regional distribution in different forms of cataract. AB - The content of glutathione is high in the anterior lens cortex (plus epithelium) and the posterior lens cortex, whereas it is substantially lower in the lens nucleus. A decrease of glutathione in the lens cortex does not occur with lenses from adults up to the highest age. The glutathione content is highest in the cortex of clear fresh lenses and shows a decrease with deep supranuclear cataract, primary nuclear cataract (cataracta brunescens nigra) and clear lenses post-mortem (approximately 20 hr). The subcapsular cataract, especially with additional secondary nuclear cataract, with cataracta matura or intumescens, shows a rapid and pronounced progressive decrease in the glutathione content. PMID- 2307193 TI - Chemical and pharmacological properties of MK-927, a sulfonamide carbonic anhydrase inhibitor that lowers intraocular pressure by the topical route. AB - A large number of sulfonamides have now been tested by the topical route for the lowering of intraocular pressure in the normal albino rabbit. Certain compounds with favorable balance between lipid and water solubility, and high activity against carbonic anhydrase, do lower pressure as much as 3 mmHg. MK-927, a thienothiopyrane-2-sulfonamide carrying an alkylamino group of pK 5.8, has desirable physicochemical properties: good water solubility below pH 5.8, a CHCl3/buffer ratio of 0.6 at pH 5.4, and a KI value against carbonic anhydrase of 2-7 nM, depending on assay conditions. Inhibition of CO2 hydration is non competitive. By comparison with other candidate topically active sulfonamides, it is the most effective in terms of pressure lowering times duration of action. There are no apparent systemic effects or ocular toxicity. The concentration of drug reaching the ciliary process and aqueous humor is of the same order as that following parenteral sulfonamides, so that inhibition of the enzyme exceeds 99%. MK-927 is therefore a candidate for the clinical treatment of glaucoma. PMID- 2307194 TI - Sialic acid in human tear fluid. AB - A simple assay for the determination of sialic acid (N-acetylneuraminic acid) in human tear fluid was evaluated. Sialic acid, terminally bound on carbohydrate side-chains of glycoproteins, was released after treatment with neuraminidase and measured by an enzymatic colorimetric test. Tear fluid samples were collected from ten healthy adults, using glass capillaries and cellulose sponges. Sialic acid levels in tears collected with sponges (0.8-1.8 mmol l-1) did not differ significantly from those found in capillary tears (0.9-1.8 mmol l-1). Sialic acid, expressed as mmol g-1 protein, was significantly lower in tears collected with sponges (0.18-0.32 mmol g-1) than with capillaries (0.19-0.42 mmol g-1). Recovery of sialic acid and protein after incubation of cellulose sponges with tears was more than 99%. Sialic acid levels in human tears, which had been centrifuged to remove insoluble material, remained unchanged. Furthermore, tear sialic acid activity did not pass a filter with a molecular weight cut-off point of 10,000. Our data indicate that with the assay used in this report, sialic acid in tears is not due to secretory immunoglobulin A (sIgA), lactoferrin and lysozyme. The fact that the major tear proteins do not contribute to the sialic acid levels detected in tears suggests that other as yet unknown soluble glycoproteins are involved. PMID- 2307195 TI - Age-dependent changes in monkey lenticular gangliosides. AB - The content, composition, and distribution of gangliosides were examined in the lenses of normal rhesus monkeys aged 6-16 years. Gangliosides were isolated by organic solvent extraction. DEAE-Sephadex ion-exchange column chromatography, and thin-layer chromatography (TLC). Ganglioside contents determined by the thiobarbituric acid method increased in the lens with aging. TLC analysis of gangliosides showed a much more complex pattern with aging, and the predominant gangliosides were tentatively identified as GM3, GM1, and GD1a. Individual lenticular gangliosides were identified by TLC-immunostaining procedures using anti-GM1 and anti-asialoGM1 antisera. PMID- 2307196 TI - Cohesive strength of corneal lamellae. AB - Strips of rabbit stroma were prepared, and the force required to tear them apart along their length was determined. This amounted to an average of 10 g mm-1 width of tissue and it is independent of the depth of the plane in which the splitting of the cornea takes place. It could not be determined, however, whether the cohesive strength of the tissue is due to occasional collagen fibrils binding it together, interweaving of the lamellae or enmeshing of the collagen fibrils by ground substances. Other corneas were split by blunt dissection in vivo and allowed to recover for various periods of time, when the reformed strength of the split was measured. It was found to be negligible for about 5 days and rose quickly to 0.25-0.5 of the value of the untouched cornea. No increase in the force of adhesion of the split stroma was observed if an extract of corneal epithelium or a suspension of platelets was injected into the wound. PMID- 2307197 TI - On the etiology of subcapsular lenticular opacities produced in dogs receiving HMG-CoA reductase inhibitors. AB - The administration of high dosages of various hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors has resulted in the development of subcapsular lenticular opacities in dogs. While dogs receiving cataractogenic doses of HMG-CoA reductase inhibitors experienced profound decreases in circulating serum cholesterol concentrations (40-60% reductions in total serum cholesterol), a causal relationship between serum cholesterol lowering and cataractogenesis was not established. A strong relationship was demonstrated, however, between the systemic exposure to inhibitor (plasma drug levels) and the cataractogenic potential of the various compounds studied. Analysis of lenses from dogs chronically dosed with various HMG-CoA reductase inhibitors revealed the presence of low drug levels in the lens (less than 500 ng equivalents g-1), but no correlation was observed between the amount of drug associated with the lens after chronic treatment and cataract development. In addition, no abnormalities in cholesterol content or sterol composition were observed in clear and/or cataract containing lenses from dogs chronically dosed with HMG-CoA reductase inhibitors. The kinetics of drug appearance in the aqueous and lens cortex was assessed after doses of various HMG-CoA reductase inhibitors, and suggested somewhat higher but not statistically significant peak concentrations of inhibitor were achieved by compounds which produced a higher incidence of cataracts. These data have suggested that high doses of HMG-CoA reductase inhibitors may increase lenticular exposure to drug via the aqueous humor by producing a substantial systemic exposure to drug substance. This may result in an increased concentration of inhibitor in the outer cortical region of the lens where cholesterol synthesis is critical, thereby resulting in the development of opacities. The production of lenticular changes by a HMG-CoA reductase inhibitor of diverse chemical structure establishes, with reasonable assurance, that these lens changes are mechanism based (i.e. a product of the biochemical mechanism of action of this class of compounds). An extrapolation of these findings to patients receiving therapeutic dosages enables a favorable risk evaluation since the doses to be employed clinically are much lower and result in a far lower systemic exposure to drug substance. PMID- 2307198 TI - Photoreceptor survival-promoting activity in interphotoreceptor matrix preparations: characterization and partial purification. AB - It is well established that many types of cells are dependent on trophic factors for their survival. We are investigating whether photoreceptor survival may also be dependent upon such a factor, as well as the possibility that the interphotoreceptor matrix (IPM), which lies between the outer retina and the RPE, may be a source of photoreceptor survival-promoting activities. Well characterized cultures of embryonic chick retinal neurons and photoreceptors, in which the photoreceptors spontaneously degenerate between 7 and 10 days in culture, were used to test this hypothesis. Crude extracts of IPM were found to support three- to fourfold increases in photoreceptor survival in 10-day cultures. This response was dose-dependent, saturable, and specific for photoreceptors, since there was no difference in the number of non-photoreceptor neurons between treated and control cultures. This photoreceptor survival promoting activity (PSPA) may function when present either as a substratum-bound molecule or as a medium supplement. PSPA is heat labile, sensitive to freeze thawing, and stable only within a very narrow pH range. The activity binds to heparin affinity columns but, in contrast to the behavior of growth factors such as FGF, it can be eluted from the columns at low salt concentrations (0.5 M NaCl). PSPA is eluted from a Sephacryl S-200 gel filtration column in two regions with Mr = 400-450 kDa and 33 kDa, respectively. SDS-gel electrophoresis suggests that the high molecular weight activity is composed of aggregates of lower molecular weight molecules. While this factor has not been purified to homogeneity, the combination of heparin-agarose affinity chromatography and hydrophobic interaction chromatography on phenyl-Sepharose columns results in 720 fold purification of the activity, with one unit of PSPA activity corresponding to 40 ng protein. This partial purification is accompanied by substantial reduction in the complexity of protein patterns in silver-stained SDS-gels. These findings are potentially important since a macromolecular factor promoting photoreceptor survival could play a role in the normal development of the retina, and could also further our understanding of retinal degenerations such as retinitis pigmentosa. PMID- 2307199 TI - Metabolic labeling of rod outer segment phospholipids in miniature poodles with progressive rod-cone degeneration (prcd). AB - The recessive genetic defect in miniature poodles which results in progressive rod-cone degeneration (prcd) has been investigated in an attempt to determine the biochemical abnormality involved. In the present study, the rod outer segments of young prcd affected miniature poodles and normal dogs have been compared with respect to the incorporation of intravitreally injected [3H]palmitic acid. [14C]linolenic acid, and [14C]docosahexaenoic acid into neutral lipids and phospholipids as well as [3H]palmitate and [14C]leucine into rhodopsin. In addition, 3 mm trephined punches of retinas were incubated with [3H]palmitic acid, [3H]arachidonic acid, [14C]linolenic acid, [3H]serine, [14C]glycerol and [14C]leucine. No difference in incorporation of labeled precursors into lipids or rhodospin was noted between prcd affected and normal retinas. Phosphatidyl choline appeared to function as a carrier of fatty acids to the rod outer segment where they were redistributed to other phospholipids. An interesting lack of conversion of the essential fatty acid linolenic acid to docosahexaenoic acid was noted in both normal and affected retinas. This conversion involves elongation and desaturation of linolenic acid and may take place primarily in extraretinal tissues such as the liver. This finding, in conjunction with a parallel study of plasma fatty acids which has shown significantly lower levels of docosahexaenoic acid in prcd affected poodles, points to a possible systemic defect in the metabolism or transport of docosahexaenoic acid, a fatty acid uniquely enriched in the photoreceptor outer segments. PMID- 2307200 TI - Metabolic inhibitors reversibly alter the basal membrane potential of the gecko retinal pigment epithelium. AB - The effects of metabolic inhibitors on the apical and basal membrane potentials were studied in the isolated retinal pigment epithelium of the lizard Gekko gekko. Adding dinitrophenol or cyanide or cooling the tissue to 15 degrees C first depolarized the apical membrane and then hyperpolarized the basal membrane. The basal hyperpolarization was accompanied by an apparent increase in basal resistance. These effects were fully reversible. Adding ouabain to inhibit specifically the apical Na(+)-K+ pump irreversibly depolarized the apical membrane but did not produce a basal membrane hyperpolarization. Dinitrophenol, cyanide and azide also reversibly inhibited a basal membrane response that was evoked by changing the apical potassium concentration. Ouabain did not inhibit this potassium-evoked basal response. These results suggest that metabolic inhibitors will be useful tools to study RPE basal membrane function. PMID- 2307201 TI - Limited recovery of striatal dopaminergic fibers by adrenal medullary grafts in MPTP-treated aging mice. AB - Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages the dopaminergic (DA) nigrostriatal system in C57BL/6 mice. We have investigated the effect of MPTP neurotoxicity and subsequent adrenal medullary grafts into the striatum of young (2-3 months) and aging (12 months) mice. MPTP treatment (4 X 20 mg/kg ip given 3 or 12 h apart in young mice and 12 h apart in aging mice) resulted in 80-90% depletion of striatal DA and virtual disappearance of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in both young and aging mice 1 week following treatment. Only partial recovery of TH-IR fibers was seen 5 weeks after MPTP treatment in young mice, while virtually no recovery was seen in aging mice. Adrenal medullary minced pieces were grafted into the striatum of young and aging mice 1 week after MPTP treatment. In young mice, dense TH-IR fibers were observed in the striatum on the grafted side 4 weeks later, far denser than those in sham operated striatum. Although this staining was most prominent around the grafts, many TH-IR fibers also were found in the ventral striatum close to the nucleus accumbens. No such increase in TH-IR fibers was found on the nongrafted side. DA concentration on the grafted side recovered to 45% of the control level. In aging mice receiving similar grafts, TH-IR fibers also were observed in the grafted striatum, but were less dense and more restricted around the site of the graft compared with young mice. DA concentration on the grafted side was 29% of the control level. We conclude that the MPTP-depleted nigrostriatal DA system in aging mouse brain can recover partially following adrenal medullary grafts, but the degree of recovery is more limited compared with that in young brain. PMID- 2307202 TI - Analysis of axonal regeneration through the silicone regeneration chamber: a retrograde tracing study in the rabbit facial nerve. AB - Transected facial nerve buccal branches in the adult rabbit were sutured to a silicone growth chamber and regeneration was observed at 3, 5, and 7 weeks postoperation. Using the retrograde axonal transport of horseradish peroxidase technique the soma in the facial motor nucleus were counted and the number was correlated with the number of axons found in the mid-cross section of the regenerating buccal branch and with the number of axons in the original nerve. The somatotopic reorganization in the facial motor nucleus was examined. The mean number of facial motoneuron soma labeled with HRP in the control was 68.0% (+/- 18.6, SE) of the axons counted at periphery. In the regenerating nerves, the labeled soma represented 2.4% of the preoperative controls after 3 weeks and rose to 8.6 and 43.9% at 5 and 7 weeks, respectively. At 3 weeks postoperative time, four of six regenerating nerves did not contain any myelinated axons at the center cross section. The ratios of labeled soma to the regenerating myelinated axons counted at the center cross section at 5- and 7-week time points were 42.2 and 61.1%, respectively. The location of the soma found in the early regeneration phase was similar to the normal distribution except in the dorsal subnucleus. After 7 weeks the proportion of labeled soma in the intermediate subnucleus declined but the general pattern replicated the distribution found in normal control preparations. PMID- 2307203 TI - Putrescine content and structural defects in isolated fractions of rat brain after reversible cerebral ischemia. AB - Reversible cerebral ischemia was produced in rats by occluding both vertebral and both carotid arteries. Following 30 min of ischemia, brains were recirculated for 24 h. The hippocampus, the striatum, and the cortex were sampled, homogenized, and fractionated on a discontinuous sucrose gradient. The fractions were evaluated morphologically by electron microscopy and biochemically by measuring the activity of marker enzymes. Putrescine was extracted from the isolated fractions and measured quantitatively using HPLC and a fluorescence detector. In the total tissue homogenate of control animals putrescine content amounted to 72.0 +/- 3.1, 70.2 +/- 7.6, and 72.7 +/- 2.1 pmol/mg protein in samples prepared from the cortex, the hippocampus, and the striatum, respectively. In the mitochondrial fraction the content was lower, while in the synaptosomal fraction and in myelin it was higher than that in total tissue homogenate. Following cerebral ischemia there was a 6- to 10-fold increase in putrescine in tissue homogenate: In the cortex it increased to 429 +/- 24 pmol/mg protein, in the hippocampus to 585 +/- 70 pmol/mg protein, and in the striatum to 718 +/- 98 pmol/mg protein. Among the isolated fractions the highest levels of putrescine were found in synaptosomes from the striatum (663 +/- 196 pmol/mg protein), followed by the hippocampus (500 +/- 125 pmol/mg protein) and the cerebral cortex (349 +/- 45 pmol/mg protein). This order correlated to the degree of morphological injury which was most pronounced in the striatum and the hippocampus and less in the cerebral cortex. The results of the present study provide further evidence of a relationship between postischemic putrescine levels and the extent of ischemia-induced neuronal injury. PMID- 2307204 TI - The effects of acidosis on chronically hypoxic neurons in culture. AB - Neuropathologic changes associated with perinatal hypoxic-ischemic events in the human infant most often result from chronic hypoxia rather than from acute asphyxia. To characterize the effects of acidosis associated with chronic hypoxia in developing neurons, cerebral cortical cultures obtained from fetal mice were exposed to 5% O2 continuously for either 24 or 48 h at 10 days after plating. At the conclusion of the hypoxic insult (HI), neuronal morphology was relatively intact for both conditions even though culture medium reflected significant reductions in pH and bicarbonate with elevation of lactate; cultures exposed to the longer HI manifested statistically greater aberrations from control values. Total benzodiazepine (BDZ) binding and clonazepam (CLO)-displaceable BDZ binding, reflecting the neuronal component of the receptor, were only modestly reduced immediately after HI, but were thereafter significantly and progressively lower over the 72 h normoxic recovery period. Although neuronal integrity was progressively diminished with both insults, morphology was always more normal and CLO higher in cultures subjected to 48-h HI compared to the 24-h HI (34.0 +/- 9.8 vs 1.8 +/- 1.1% of control values at 72 h, respectively; P less than 0.001). In contrast, values obtained for the glial marker Ro5-4864-displaceable BDZ binding were higher than control values for both conditions. Outcome was not influenced by removal of acidotic medium, nor by normalization of lactate. These data suggest that, with time, neurons in vitro adapt to severe hypoxia and that alterations in pH, lactate, and bicarbonate by themselves are probably not neurotoxic since the most acidotic cultures exhibited improved survival. PMID- 2307206 TI - 22nd annual meeting of the Swiss Societies for Experimental Biology (USGEB/USSBE). March 15/16, 1990, Zurich, ETH-Honggerberg. PMID- 2307205 TI - The midsagittal area of the corpus callosum and total neocortical volume differ in three inbred strains of mice. AB - Differences in the midsagittal area of the corpus callosum have been reported between human males and females, between handled and nonhandled rats, and both within and between various strains of mice. This measure has, in addition, been related to handedness in humans and "pawedness" in certain strains of mice. The present study investigated the between- and within-strain differences in three inbred strains of mice, two with autoimmune disorders and spontaneously occurring developmental neuropathology, in the midsagittal area of the corpus callosum, the total neocortical volume, and the asymmetry of the neocortex. These morphometric measures were obtained from coronally sectioned celloidin-embedded material from New Zealand Black (NZB/BINJ), BXSB/MpJ, and DBA/2J mouse strains. NZB mice had a total neocortical volume larger than that of either the BXSB or DBA strains, whereas the BSXB mice had a midsagittal area of the corpus callosum larger than that of either of the other two strains. In addition, there was a positive correlation between these two measures. There was no correlation between total neocortical asymmetry and midsagittal area of the corpus callosum in any of the three strains. Finally, there were no differences in any morphometric measure between animals with or without developmental neuropathology in any given strain. PMID- 2307207 TI - Effect of hyperlipidemic serum and irradiation on wound healing in primary quiescent cultures of vascular cells. AB - After 8 weeks in culture, outgrowths from explants of aortic media of rhesus monkeys and New Zealand rabbits result in circular colonies of mature smooth muscle cells, quiescent in 10% serum. Such cultures were wounded by cutting out a 1.5-mm-wide strip. Migration of cells into the wound area was measured daily, and proliferation was assessed by [3H]thymidine incorporation. Migration began within 24 hr and at 7 days the defect was filled by proliferates of migrated cells. The cumulative labeling index was highest in the cells in the wound gap but was also increased in the remaining part of the culture. Wounding thus stimulated the uninjured portion of these primary cultures to proliferate, while in subcultures of these cells increase in [3H]thymidine incorporation was confined to the wound area. While hyperlipidemic serum has been shown to induce proliferation in unwounded cultures, it did not enhance cell replication elicited by wounding but reduced cell density and labeling index in the wound gap. Irradiation prior to wounding reduced cell proliferation to control values, while migration of cells was not significantly affected. In irradiated cultures, the inhibitory action of hyperlipidemic serum on cell migration became evident. Such quiescent cultures thus allow us to separate the effects of a specific injury on the proliferative and migratory responses of vascular smooth muscle. PMID- 2307208 TI - Survival of rabbit platelets exposed to immune complexes. AB - Rabbits injected with human serum albumin (HSA) formed detectable immune complexes after 5 days; complex formation was maximal between 11 and 14 days after which the complexes were cleared from the circulation. Platelets from control rabbits or HSA-injected rabbits had a reduced survival upon injection into rabbits in which complexes were forming. Platelets from HSA-animals tended to survive for a longer period upon injection into control rabbits than when they were injected into HSA-rabbits, raising the possibility that some of the immune complexes may have eluted from their surface. Platelets prepared from either control animals or from HSA-treated animals at the time when complexes were being cleared from the circulation (14-21 days) did not have a shortened life span in HSA- or control rabbits. When platelet survival was reduced, it could not be attributed to platelet accumulation at sites of vessel wall injury or to accumulation in kidneys damaged by immune complexes, since the tissues (aorta and kidney) appeared to be morphologically normal and free of thrombi. The reduction in platelet survival likely results from the interactions of immune complexes with the surface of platelets leading to the platelets being recognized as "foreign" and cleared from the circulation by the reticuloendothelial system. PMID- 2307209 TI - Quantitative X-ray microanalysis of alveolar macrophages after long-term treatment with amiodarone. AB - Treatment with the iodine-containing antiarrhythmic drug, amiodarone, can cause pulmonary toxicity. Alveolar macrophages are particularly susceptible to formation of lipidrich lamellar bodies in amiodarone-treated animals. Amiodarone and several of its metabolites accumulate in the cell. Previously, we have reported that the technique of X-ray microanalysis is useful in monitoring the distribution of iodine in freeze-dried cryosections of alveolar macrophages from Fischer 344 rats 24 hr after a single dose of amiodarone. In the present study, we examine the effects of longer term amiodarone treatment of 1 or 9 weeks. Substantial changes in iodine distribution occur in the cells with increasing length of drug treatment. High concentrations of iodine are found early in the lamellar bodies. The iodine levels in the nuclei slowly increase with the length of treatment, and after 9 weeks of treatment, approach those found in the lamellar bodies. It is possible that this accumulation of iodine in the nuclei is due to the presence of polar metabolites. In addition, the potassium concentration in the cell decreases and the sodium increases with treatment duration. These changes in cations are most likely due to altered ion transport in the macrophages by the inhibition of membrane Na-K-ATPase by the drug and its principal metabolite, desethylamiodarone. PMID- 2307210 TI - Abnormal accumulation of elastin-associated microfibrils during elastolysis in the arterial wall. AB - We examined the correlation between elastolysis and abnormal accumulation of microfibrils in the arteries of rabbits using light and electron microscopic and tissue culture techniques. Partial constriction of the common carotid arteries of rabbits gave rise to gradual atrophy of the media with elastolysis and an unusual accumulation of microfibrils. With advancing experimental atherosclerosis in cholesterol-fed rabbits, the elastofibrotic intima generally became thick and hyalinized and was replaced by bundles of microfibrils lacking elastin or associated with only tiny elastin aggregates and disrupted elastic fibers. Organ cultures of aortic explants from rabbits with or without pancreatic elastase supplementation for 5 days disclosed that there was complete loss of medial elastic fibers and increasing deposition of microfibrils, morphologically identical to elastin-associated microfibrils, around viable smooth muscle cells only in the elastase supplemented group. These observations suggest that abnormal accumulation of microfibrils in the elastic tissue is closely associated with excessive elastolysis of preformed or newly formed elastic fibers during elastic tissue remodeling. Enhanced synthesis of microfibrils may occur in response to elastolysis as a reparative phenomenon. PMID- 2307212 TI - The effects of lathyrogens on intestinal anastomoses in the rat. AB - Submucosal collagen provides strength to the intestinal wall. In order to assess the importance of collagen fibers for the developing strength of intestinal anastomoses we have sought to prevent postoperative collagen crosslinking by administration of lathyrogens. Rats, receiving both an ileal and a colonic anastomosis, were treated with either D-penicillamine or beta-aminopropionitrile from 1 day before operation. Animals were sacrificed 7 days postoperatively and bursting pressures, bursting sites, and anastomotic collagen (hydroxyproline) content and solubility were determined. D-Penicillamine, in a dose of 500 mg/kg/day and administered orally, had no effect at all. beta-Aminopropionitrile, in a dose of 625 mg/kg/day and given orally or intraperitoneally, significantly increased the acid solubility of anastomotic hydroxyproline in both ileum and colon without affecting total hydroxyproline content or concentration. Bursting pressures of the anastomotic segments were lowered, more significantly in colon than in ileum. Also, the bursting site was found more frequently in the anastomotic area in these animals. By inhibiting the formation of crosslinks in intestinal wounds with beta-aminopropionitrile, the anastomotic strength was reduced. These results demonstrate the importance of collagen in maintaining anastomotic integrity and at the same time emphasize that not only the quantity but also, and perhaps even more so, the quality of the collagen should be taken as an index of healing. PMID- 2307211 TI - Changes in myofibrillar components after skeletal muscle necrosis induced by a myotoxin isolated from the venom of the snake Bothrops asper. AB - The effects of a myotoxic phospholipase A2 isolated from the venom of the crotaline snake Bothrops asper on skeletal muscle myofibrils were studied by histological, ultrastructural, immunohistochemical, and biochemical parameters. Myotoxin induced a rapid and prominent muscle necrosis after intramuscular injection in mice. In this process, myofibrils were affected and three main changes were observed: (A) Initially, they were hypercontracted, eventually forming "clumped," dense masses which alternated with spaces devoid of myofilaments in the cytoplasm. This initial stage is probably due to hypercontraction resulting from a calcium influx after toxin-induced sarcolemmal damage. (B) A second change occurred between 3 and 6 hr, when the clumped or hypercontracted pattern changed to a "hyaline" pattern in which myofilaments were relaxed and had a more uniform distribution in the cellular space. Although there was not a widespread degradation of myofibrillar components at this stage, desmin started to be lost in samples obtained as early as 15 min after toxin injection, and alpha-actinin was almost absent by 7 hr. Thus, it is proposed that this shift may be due to a selective proteolytic degradation of structurally relevant components, particularly alpha-actinin. As a consequence, the mechanical integration of myofilaments is impaired, precluding hypercontraction. (C) Finally, at later time periods (24, 48, and 72 hr), there was widespread degradation of myofibrillar proteins, probably caused by proteases derived from inflammatory cells such as neutrophils and macrophages, whose numbers in necrotic muscle increased markedly at these time periods. PMID- 2307213 TI - Serum antielastase deficiency in tight-skin mice with genetic emphysema. AB - The tight-skin (Tsk) mouse is a model of genetically determined emphysema. The cause for the development of the lung lesion is unknown. In the present study we investigated the lung morphometry and the serum elastase inhibitory capacity (EIC) of Tsk mice. Mean interalveolar distance was significantly greater (+60%) in Tsk mice than in C57 Bl/6J, NMRI, and Balb/c mice, which have similar values. Serum of Tsk mice against mouse leukocyte elastase (MLE) has significantly lower EIC values than that of NMRI, Balb/c (-64%), and C57 Bl/6J (-50%) mice. Similar results were obtained when porcine pancreatic elastase (PPE) was used. Against human leukocyte elastase (HLE), however, there was no difference among the strains, all of which had high EIC values. Preincubation of mouse (C57 Bl/6J) serum with chloramine-T (CT) resulted in an almost complete inhibition of EIC against MLE and PPE but only in a 20% inhibition against HLE using a synthetic substrate. Using elastin Congo Red as substrate, CT inhibited EIC against MLE and PPE by approximately 70% but did not affect the EIC against HLE. These results indicate that (1) the Tsk mouse can be considered a model of severe inborn deficiency of serum antielastase activity which is associated with emphysema; and (2) MLE and PPE can be considered interchangeable in studies of serum EIC in the mouse. On the other hand, the differences between MLE and HLE preclude the use of HLE for EIC determination in this species. PMID- 2307214 TI - Determination of desmosines in elastin-related skin disorders by isocratic high performance liquid chromatography. AB - Abnormalities in the amount of skin elastin occur in several cutaneous disorders. The number of elastic fibers is increased in elastotic disorders such as pseudoxanthoma elasticum (PXE) and cutis rhomboidalis nuchae (actinic elastosis, AE) and is decreased in elastolytic disorders such as cutis laxa (CL). We describe a procedure to quantify desmosines and elastin in small amounts of skin using high-performance liquid chromatography (HPLC). Biopsies were obtained from normal, nonsolar exposed skin and from the lesional skin of patients with PXE, cutis rhomboidalis nuchae, and CL. Specimens were subjected to hot alkali treatment and the desmosines were released by acid hydrolysis and quantified by HPLC. The mean value for normal skin was 252 +/- 28 ng desmosines per milligram wet weight (SD, n = 5). The disorders of elastosis (PXE and AE) demonstrated a two- to fivefold increased content of desmosines. In contrast, the elastolytic disorder (CL) had only 20% of the normal content of desmosines. Furthermore, PXE and normal skin elastins had the same amount of desmosines per milligram purified elastin. This method could be used to evaluate the extent of elastosis or elastolysis in a particular lesion. PMID- 2307215 TI - Extracellular matrix changes following blunt trauma to rat skeletal muscles. AB - Myofiber injury-repair was studied in the rat following blunt trauma to the lower leg in order to understand how the inflammatory and regenerative responses of muscles are altered when myofiber rupture is accompanied by bleeding and clotting reactions. A contusion injury to the muscles of the lower hindlimb of the rat was induced by applying an impact force of 4.7 N-m/cm2 to one leg. The gastrocnemius and soleus muscles were removed bilaterally and evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations for several days following insult (6-120 hr). A significant increase in wet weight of the gastrocnemius muscle was noted 24 hr postinjury as fluid accumulation and bruising were evident in the muscles resulting from bleeding and inflammation. Vascular disruption was confirmed by the localization of some plasma constituents (fibrinogen, albumin, and complement C3) throughout the interstitial space and even inside some of the damaged myofibers. Inflammation was present and persisted for 5 days as evidenced by continued mast cell degranulation and increased vascular permeability. Using antibodies to identify specific proteoglycans which appear or disappear at various times during muscle regeneration, muscle repair could be followed. The repair process required approximately 10 days for restoration of morphologically intact myofibers. Thus, myofiber repair processes appear to be maintained even after disruption of the vascular system and ischemia following blunt trauma. PMID- 2307216 TI - Effects of vinblastine, leucine, and histidine, and 3-methyladenine on autophagy in Ehrlich ascites cells. AB - The microtubule inhibitor vinblastine causes accumulation of autophagic vacuoles in many cell types. In hepatocytes, many of the accumulated vacuoles are nascent, which has been interpreted to suggest that vinblastine acts by inhibiting the fusion of hydrolase-containing lysosomes with early autophagic vacuoles. However, our previous results suggested that, in Ehrlich ascites cells, vinblastine causes accumulation mainly of older autophagic vacuoles (AVs). This study was undertaken to further characterize the mode of action of vinblastine in these cells. The vinblastine-accumulated AVs were quantified by electron-microscopic morphometry. In addition, the effects of inhibitors of autophagic segregation (leucine, histidine, and 3-methyladenine) on the vinblastine-induced accumulation of autophagic vacuoles were studied. Protein degradation was measured using [14C]valine. Vinblastine caused accumulation of advanced autophagic vacuoles but did not increase the rate of protein degradation. The volume density of early vacuoles remained at the control level. The amino acids retarded but did not prevent the accumulation of autophagic vacuoles, whereas 3-methyladenine almost completely prevented the accumulation. The results suggest that in Ehrlich ascites cells vinblastine acts by inhibiting the maturation of advanced autophagic vacuoles into residual bodies and by stimulating the formation of new autophagic vacuoles. However, 3-methyladenine almost completely prevents the formation of new autophagic vacuoles in the presence of vinblastine. In conclusion, in Ehrlich ascites cells, vinblastine does not prevent the entry of hydrolases into autophagic vacuoles. This calls into question the importance of microtubules in the transport of lysosomal enzymes into autophagic vacuoles. PMID- 2307217 TI - Serum erythropoietin and erythropoiesis in patients with myelodysplastic syndromes. AB - Ineffective erythropoiesis is an early feature of the myelodysplastic syndromes (MDS), usually accompanying an hypercellular marrow. In a previous study, concentrations of serum erythropoietin (EPO) in MDS have been shown to correlate inversely both with haemoglobin concentration and with % bone marrow erythroblasts. We have measured erythroid production using a radioisotopic technique in 20 patients with MDS. Although haemoglobin concentration shows a weak inverse relationship with serum EPO concentration there is considerable variation in EPO concentration at a given haemoglobin level. There is no correlation between serum EPO and total erythroid production, though there is a weak correlation with effective erythropoiesis. The data suggests that control mechanisms of erythropoiesis in patients with MDS are complex. PMID- 2307218 TI - Reversal of myelofibrosis by hydroxyurea. AB - Bone marrow morphology in 39 symptomatic patients with myeloproliferative disorders (polycythaemia vera 15, essential thrombocythaemia 14, idiopathic myelofibrosis 9, myeloproliferative syndrome 1) and elevated platelet counts was studied before and after a median of 18 months of continuous treatment with hydroxyurea. We found a significant reduction of bone marrow fibrosis, believed to be mediated by suppression of thrombopoiesis by hydroxyurea. PMID- 2307219 TI - Platelet calmodulin correlates with platelet turnover. AB - We measured the calmodulin content in platelets in 13 normal persons and in 62 patients with hematological diseases. The level of platelet calmodulin was higher in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus, myeloproliferative disorders, acute leukemia in a recovery phase, aplastic anemia, thrombosis and hypersplenism as compared to the controls. Among the patients with ITP, calmodulin was lower in responders than in nonresponders and those at the initial diagnosis. We also measured the volume, life-span and aggregation of the platelets and demonstrated a significant relationship between the calmodulin level and the platelet volume, and a negative relationship between the calmodulin level and platelet life-span, there was no correlation between the calmodulin level and platelet aggregation. We thus conclude that platelet calmodulin is inversely correlated with platelet turnover. PMID- 2307220 TI - Hypoxia and deposition of iron in liver and spleen of mice given iron supplement. AB - Iron-related changes in peripheral blood and variations in liver and spleen iron concentrations during alternating periods of hypoxia and normoxia have been investigated in iron-supplemented mice by chemical and histological methods. During hypoxia, packed cell volume increased from 40 to 70%. The iron content of the liver increased during the first hypoxic and the following normoxic period, while an increase in spleen iron started after the first hypoxic period. Transferrin saturation fell from about 60 to about 20% during hypoxia and normalized during normoxia. Hypoxia together with iron supplementation led to increased erythropoiesis and parenchymal iron deposition in liver. The reduction in transferrin saturation may be attributed to the effective uptake of iron by hepatocytes simultaneously with the erythropoiesis. The spleen seemed to participate in the production of red cells during hypoxia. The increase in spleen iron during normoxia can be explained by the role of the spleen in the catabolism of excess erythrocytes. PMID- 2307221 TI - An immunomorphometric study on megakaryocyte precursor cells in bone marrow tissue from patients with chronic myeloid leukemia (CML). AB - An immunomorphometric study was performed on trephine biopsies of the bone marrow in 41 patients with chronic myeloid leukemia (CML) to determine number and size of megakaryocytic precursor cells (pro- and megakaryoblasts). For specific staining, a monoclonal antibody against platelet glycoprotein IIIa (Y2/51) was employed which is applicable on routinely fixed and paraffin embedded tissue. In comparison with control specimens from 15 patients, in CML morphometric analysis revealed an increase in the total amount of megakaryocytes per square and cubic millimeter marrow tissue, but particularly in patients with thrombocythemia. Moreover, a non-disorderly expansion of the megakaryocyte precursor pool was recognizable by showing a relative frequency of pro- and megakaryoblasts in congruence with the normal value. In this context a significant correlation between the counts for Y2/51-positive megakaryocytic elements and promegakaryoblasts with the corresponding platelet values was encountered. The more mature stages of megakaryopoiesis (pro- end megakaryocytes) disclosed a relevant shift to smaller cell forms with rounded cell perimeters and a more compact aspect of their nuclei. Additionally, in 6 patients with CML, evolution into a subacute and manifest (micro)-megakaryoblastic transformation accompanied by myelofibrosis could be demonstrated by a retrospective review of file material. PMID- 2307222 TI - White-cell counts in childhood acute lymphoblastic leukemia. PMID- 2307223 TI - Treatment of cytophagic histiocytic panniculitis with combination chemotherapy. PMID- 2307224 TI - Systemic lupus erythematosus associated with refractory anemia with excess of blasts. PMID- 2307226 TI - Structure of the DNA binding wing of the gene-V encoded single- stranded DNA binding protein of the filamentous bacteriophage M13. AB - The structure in solution of a beta-loop in mutant Y41H of the single-stranded DNA binding protein encoded by gene-V of the filamentous phage M13 has been elucidated using 2-dimensional 1H-nuclear magnetic resonance techniques. Furthermore, these studies enabled us to demonstrate that an identical structural element is present in wild-type gene-V-protein and that this element intimately is involved in the binding of gene-V-protein to single-stranded DNA. It is shown that the structure of the DNA binding wing deviates from that proposed for the same amino acid sequence on the basis of X-ray diffraction data. The structure is, however, identical to that of the DNA binding wing present in the single stranded DNA binding protein encoded by the genome of the evolutionary distantly related filamentous phage IKe. The latter observations support our current view that in the binding of these proteins to single-stranded DNA a common structural motif is involved. PMID- 2307225 TI - Characterization of a new malignant human T-cell line (PFI-285) sensitive to ascorbic acid. AB - A new malignant human T-cell line-labelled PFI-285-has been isolated from a boy with malignant lymphoma. Morphologically, the cells had characteristics of malignant lymphoid cells. The cells presented surface antigens as early cortical lymphocytes and proliferated non-adherently as single cells, independent of T cell growth factor (IL-2), in liquid culture. The cells had undetectable levels of receptors for IL-2, were not clonogenic in soft agar, but did form tumors in nude mice. Their establishment and continuous growth in vitro was dependent on the number of cells inoculated and on the growth medium used. Cytogenetic alteration, HTLV-1 or reverse transcriptase activity were not detected. The production of known T-cell derived lymphokines such as IL-2, B-cell growth factor(s), alpha-interferon or granulocyte/macrophage colony stimulating or inhibiting factor(s) was not detected. The cells had 5-8% natural killer (NK) cell activity against NK-cell sensitive target cells (K562) and were not sensitive for NK cells. A most unusual characteristic was the pronounced sensitivity of the cells to ascorbic acid. Concentrations down to 50 mumol/l killed the cells within hours. PMID- 2307227 TI - Partial processing of the neuropeptide Y precursor in transfected CHO cells. AB - The activation of regulatory peptides by post-translational modification of their biosynthetic precursors is generally thought to occur only in neuroendocrine cells. We have selected clones of Chinese hamster ovary cells, a non neuroendocrine cell line, which were transfected with a eukaryotic expression vector coding for the precursor for neuropeptide Y. Although the majority of the immunoreactive NPY was found in the form of pro-NPY, some degree of intracellular proteolytic processing of the precursor occurred in all clones. Part of the intracellular NPY immunoreactivity was even correctly amidated. Extracellular degradation of pro-NPY in the tissue culture medium generated immunoreactivity which corresponded in size to NPY. It is concluded that precursor processing can occur in non-neuroendocrine cells both as a biological process within the cells and as apparent processing, degradation in the tissue culture medium. PMID- 2307228 TI - Synthetic phosphopeptides are substrates for casein kinase II. AB - Casein kinase II is a protein serine/threonine kinase that exhibits a preference for acidic substrates. Previous studies have demonstrated that a glutamic acid 3 amino acids C-terminal (+3) to a serine or threonine is required for phosphorylation. To examine the ability of phosphoserine and phosphothreonine residues to serve as specificity determinants for casein kinase II, phosphopeptides containing either of these phosphoamino acids in the +3 position were synthesized and tested as substrates. Phosphopeptides containing phosphoserine in the +3 position were readily phosphorylated. In contrast, corresponding phosphothreonine-containing peptides were very poorly phosphorylated. These results imply that prior phosphorylation of substrate proteins on serine, but not threonine residues, may II. PMID- 2307229 TI - Polyamines improve Ca2+ transport system of the yeast mitochondria. AB - Spermine at concentrations of 12-100 microM considerably activates the Ca2+ transport system of the Endomyces magnusii yeast mitochondria. As a result, in the presence of spermine the mitochondria are able to decrease extramitochondrial Ca2+ to the physiological level. At Ca2+ concentrations up to 200 microM, spermine enhances the initial rate of Ca2+ uptake (a half-maximal effect at 12 microM spermine). The Ca2+ concentrations required for half-maximal Ca2+ uptake rate to be achieved were 160 and 60 microM Ca2+ without and with spermine, respectively. Spermidine is shown to be less effective (a half-maximal effect at 50-100 microM spermidine). The polyamines do not change the parameters of energy coupling of mitochondria. The data obtained enabled the yeast mitochondria to be considered to take part in regulation of cytoplasmic and matrix Ca2+. PMID- 2307230 TI - A pseudosubstrate peptide inhibits protein kinase C-mediated phosphorylation in permeabilized Rat-1 cells. AB - Activation of protein kinase C (PKC) in Rat-1 fibroblasts leads to rapid phosphorylation of an 80-kDa protein, a major substrate of PKC. Digitonin permeabilized cells perfectly supported this early response. Introduction of a PKC pseudosubstrate peptide inhibited 80 kDa phosphorylation with an IC50 of 1 microM, while a control peptide had no effect. The results indicate that this semi-intact cell system can be used in combination with the inhibitory pseudosubstrate peptide to study the involvement of PKC in cellular processes. PMID- 2307231 TI - Transforming growth factor-beta regulates the splicing pattern of fibronectin messenger RNA precursor. AB - Fibronectin (FN) polymorphism is caused by alternative splicing patterns in at least three regions (ED-A, ED-B and IIICS) of the primary transcript of a single gene. Using monoclonal antibodies, we previously demonstrated that transforming growth factor-beta (TGF-beta) preferentially increases the accumulation of the FN isoforms containing the ED-A sequence in cultured normal human fibroblasts [Balza et al., (1988) FEBS Lett. 228, 42-44]. To determine the basis of this effect, we have examined through S1 nuclease analysis, the levels of ED-A- and ED-B containing mRNAs in cultured normal human skin fibroblasts before and after TGF beta treatment. These experiments have shown that TGF-beta increases the relative amount of m-RNA for ED-A- and ED-B-containing FN isoforms. These data demonstrate that a growth factor may regulate the splicing pattern of a pre-mRNA. PMID- 2307232 TI - Further studies on the human pancreatic binary complexes involving procarboxypeptidase A. AB - In contrast to procarboxypeptidase B which has always been reported to be secreted by the pancreas as a monomer, procarboxypeptidase A occurs as a monomer and/or associated to one or two functionally different proteins, depending on the species. Recent studies showed that, in the human pancreatic secretion, procarboxypeptidase A is mainly secreted as a 44 kDa protein involved in at least three different binary complexes. As previously reported, two of these complexes associated procarboxypeptidase A to either a glycosylated truncated protease E or zymogen E. In this paper, we identified proelastase 2 as the partner of procarboxypeptidase A in the third complex, thus reporting for the first time the occurrence of a proelastase 2/procarboxypeptidase A binary complex in vertebrates. Moreover, from N-terminal sequence analyses, the 44 kDa procarboxypeptidase A involved in these complexes was identified as being of the A1 type. Only one type of procarboxypeptidase B, the B1 type, has been detected in the analyzed pancreatic juices, thus emphasizing the previously observed genetic differences between individuals. PMID- 2307233 TI - Mitogen-induced oscillations of membrane potential and Ca2+ in human fibroblasts. AB - Using the whole-cell technique, we have measured recurring hyperpolarizations induced by fetal calf serum and bradykinin in human fibroblasts. By coupling fura 2 microfluorimetry to electrophysiology, we have also measured directly cytosolic Ca2+ and found that Ca2+ oscillations occur in synchrony with membrane currents. Mitogen stimulation of cells in which intracellular K+ had been replaced with Cs+ resulted in the abolishment of the outward current. We conclude then that the mitogen-induced recurring hyperpolarizations in human fibroblasts are due to the opening of Ca2(+)-activated K+ channels. PMID- 2307234 TI - The monocarboxylate carrier from rat liver mitochondria. Purification and kinetic characterization in a reconstituted system. AB - The monocarboxylate (pyruvate) carrier was extracted from rat liver mitochondria with Triton X-100 in the presence of asolectin and partially purified by chromatography on HTP. The HTP eluate reconstituted in liposomes was shown to catalyze active pyruvatein/acetoacetateout and acetoacetatein/pyruvateout counter exchange. Kinetic characterization of the reconstituted pyruvate carrier was achieved by an original spectrophotometric method consisting of determination of substrate release from proteoliposomes with a coupled enzymatic assay. PMID- 2307235 TI - Inactivation of the uterine estrogen receptor binding of estradiol during P-450 catalyzed metabolism of chlorotrianisene (TACE). Speculation that TACE antiestrogenic activity involves covalent binding to the estrogen receptor. AB - Chlorotrianisene (TACE) exhibits in vitro little or no binding to the uterine estrogen receptor (ER) but demonstrates potent estrogenic activity in vivo, indicating that TACE is a proestrogen/proantiestrogen. Our earlier studies demonstrated that the incubation of TACE with rat liver microsomes and NADPH generates a reactive intermediate (T*) which binds covalently to proteins. The current study examined the possibility that T* may inactivate the uterine ER. The incubation of TACE with rat liver microsomes and NADPH in the presence of rat uteri, under conditions which generate T*, markedly decreased the binding capacity of the ER for [3H]estradiol (E2). The evidence indicates that ER inactivation was probably due to irreversible (covalent) binding of T* to the E2 binding site. The possibility that the antiestrogenic action of TACE and of other triphenylethylenes involves such a novel mechanism is discussed. PMID- 2307236 TI - Stimulation of nerve growth factor synthesis/secretion by 1,4-benzoquinone and its derivatives in cultured mouse astroglial cells. AB - Previously we reported that astroglial cells cultured from mouse brain synthesize and secrete nerve growth factor (NGF) and that, in quiescent cells, catecholamines markedly increase the NGF content in the conditioned medium (CM). We wished to further assess the structural properties required for exhibition of such effect of compounds containing a ring structure analogous to that of catechol on astroglial NGF synthesis. During our study, we found that hydroquinone, which was confirmed not to stimulate NGF synthesis in mouse fibroblast cells in another of our investigations, is a potent stimulator of NGF synthesis in astroglial cells and that 1,4-benzoquinone, an oxidized form of hydroquinone, is a more effective stimulator than hydroquinone itself. In addition, the results of experiments with 1,2-benzoquinone derivatives indicated that the presence of a long aliphatic side chain in the molecule eliminates the stimulatory effect of 1,4-benzoquinone on NGF synthesis in astroglial cells. PMID- 2307237 TI - Characterization of the locomotor depression produced by an A2-selective adenosine agonist. AB - Adenosine analogs, such as N6-cyclohexyladenosine (CHA) that are selective for A1 adenosine receptors, and analogs, such as 5'-N-ethylcarboxamidoadenosine (NECA) that are active at both A1 and A2 receptors, cause a profound depression of locomotor activity in mice via a central mechanism. The depression is effectively reversed by non-selective adenosine antagonists such as theophylline. We report that 2-([2-aminoethylamino) carbonylethylphenylethylamino]-5'-N ethylcarboxamidoadenosine (APEC), an amine derivative of the A2-selective agonist, CGS21680, is a potent locomotor depressant in mice. The in vivo pharmacology is consistent with A2-selectivity at a central site of action. Two parameters indicative of locomotor activity, horizontal activity and total distance travelled, were measured using a computerized activity monitor. From dose-response curves it was found that APEC (ED50 16 micrograms/kg) is more potent than CHA (ED50 60 micrograms/kg) and less potent than NECA (ED50 2 micrograms/kg). The locomotor depression by APEC was reversible by theophylline, but not by the A1-selective antagonists 8-cyclopentyltheophylline (CPT) and 8 cyclopentyl-1, 3-dipropyl-2-thioxanthine, nor by the peripheral antagonists 8-p sulfophenyltheophylline (8-PST) and 1,3-dipropyl-8-p-sulfophenylxanthine. The locomotor activity depression elicited by NECA and CHA was reversed by A1 selective antagonists. These results suggest that the effects of APEC are due to stimulation of A2 adenosine receptors in the brain. PMID- 2307238 TI - Members of the alpha-amylase inhibitors family from wheat endosperm are major allergens associated with baker's asthma. AB - We have identified the major antigens or IgE binding components from wheat flour. Thirty-five sera from patients with baker's asthma were used to analyze the reaction with wheat salt-soluble proteins. We found a 15 kDa SDS-PAGE band which reacted with all sera tested. Purified members of the alpha-amylase inhibitor family, which are the main components of the 15 kDa band, were recognized by specific IgE when tested with a pool of reactive sera. Immunodetection after two dimensional electrophoretic fractionation of crude inhibitor preparations from wheat endosperms also detected several inhibitor subunits as major low-molecular weight allergens. PMID- 2307239 TI - FAM chemotherapy +/- aminoglutethimide in the treatment of pancreatic carcinoma. AB - Human pancreas contains receptors for estrogens and androgens as well as aromatase activity. FAM chemotherapy was administered to 14 patients with pancreatic cancer (seven at Stage IV). The median survival of these patients was 24.4 +/- 4.8 weeks. FAM chemotherapy plus aminoglutethimide/hydrocortisone (AG/HC) (250 mg bid AG + 20 mg bid HC) was administered to 14 patients (seven at stage IV). The median survival of this group was 17.3 +/- 2.9 weeks (P = 0.74 vs FAM alone). We conclude that addition of AG/HC does not add to the survival of patients with carcinoma of the pancreas treated with chemotherapy. PMID- 2307240 TI - The role of parotidectomy in the treatment of nodal metastases from cutaneous melanoma of the head and neck. AB - Forty-six patients affected by head and neck melanoma were submitted to elective or therapeutic parotidectomy associated with laterocervical dissection from 1980 to 1983 at the National Cancer Institute of Milan. The study showed that parotidectomy is indicated in the presence of clinically palpable nodes or where primaries originate in the temporo-zygomatic area. It also demonstrated that survival is not affected by type of dissection performed and that cervical lymphadenectomy must always be associated with parotidectomy because of the high incidence of occult metastases in other nodal groups in these cases. PMID- 2307241 TI - Adenocarcinoma of the stomach following radical radiotherapy for testicular cancer. AB - Two male patients who underwent curative surgery and adjuvant radiotherapy (with further chemotherapy in one) for testicular cancer developed adenocarcinoma of the stomach 5 and 19 years after treatment. The stomach is included in the field of radiotherapy used to treat the para-aortic lymph nodes and this may lead to dysplastic changes in the stomach mucosa which can lead to frank malignancy. Early endoscopy should be offered to patients with dyspeptic symptoms after adjuvant radiotherapy for testicular cancer. PMID- 2307242 TI - Reflections on the new guidelines for the use of semen donor insemination. PMID- 2307243 TI - Surgical treatment of symptomatic colorectal endometriosis. AB - The approach to the treatment of bowel endometriosis has varied greatly. In this paper we present 77 consecutive patients with deep colorectal endometriosis treated with a full-thickness resection. Gynecologic procedures included conservative laparotomies for preserving fertility (39 patients); hysterectomy with bilateral salpingo-oophorectomy (29 patients); bilateral salpingo oophorectomy (2 patients); left salpingo-oophorectomy (1 patient) and resection of pelvic endometriosis in patients with previous ablative surgery (6 patients). A low anterior bowel resection was performed in 68 patients (88.3%); a disc excision of the anterior rectal wall in 5 (6.5%); sigmoid resection in 3 (3.9%), and partial cecal resection in 1 (1.3%). The postoperative febrile morbidity was 10.4%, with no apparent anastomotic leaks. Of 33 patients who attempted to conceive postoperatively, 13 achieved a term pregnancy (39.4%). Complete relief of pelvic symptoms was obtained in 38 patients (49.4%); improvement in 30 (39%); no improvement in 8 (10.4%); and worsening of symptoms in 1 (1.2%). There has been no recurrence of symptomatic bowel endometriosis during 1 to 9 years of follow-up. Full-thickness resection of the colon for the treatment of deep bowel endometriosis is a safe procedure with low morbidity, good postoperative relief of symptoms, and favorable pregnancy rates. PMID- 2307244 TI - Hysterosalpingography in the preoperative evaluation of tubal anastomosis candidates. AB - The value of the hysterosalpingogram (HSG) in the investigation of women requesting reversal of tubal sterilization has never been established. Accordingly, we reviewed the preoperative HSGs performed on 54 women and the surgical findings of these and 27 additional patients who underwent laparoscopy and/or laparotomy for tubal anastomosis. The observation of interstitial, isthmic, and ampullary obstruction by HSG correctly correlated with surgical findings in 12%, 94%, and 69% of cases, respectively. The decision to perform an anastomosis was made in 14 of 17 (82.4%) tubes with interstitial obstruction, 45 of 51 (88.2%) tubes with isthmic occlusion, and 26 of 36 (72.2%) tubes with ampullary occlusion. When distal tubal occlusion was demonstrated by HSG (36/104 tubes, 34.6%), 10 had no repairable ampullary segments. The site of tubal occlusion on HSG was not predictive of a repairable tube. We conclude that the routine HSG is not warranted in the preoperative evaluation of candidates for tubal anastomosis. PMID- 2307245 TI - Are human luteinizing granulosa cells a site of action for progesterone and relaxin? AB - Specific nuclear staining for progesterone receptor (PR) was detected by immunocytochemistry in human granulosa cells (GCs) obtained from in vitro fertilization protocols. The percent of PR-positive cells (60% to 80%) remained unchanged during 7 days of culture in media containing fetal calf serum, in the absence or presence of human chorionic gonadotropin (hCG) or the progesterone antagonist RU486. Progesterone (P) production by GCs cultured on extracellular matrix from bovine corneal endothelial cells was stimulated by hCG and prostaglandin E2 (PGE2). However, addition of RU486 or human relaxin had no effect on control, hCG-, or PGE2-stimulated P production. Thus, the receptor data are consistent with an autocrine action of P in luteinizing GCs, but initial experiments in cell culture did not define a role for P or relaxin in modulating luteal steroidogenesis. PMID- 2307246 TI - Survival and pregnancy outcome after ultrarapid freezing of human embryos. AB - Contrary to the belief that rapid cooling and thawing of mammalian embryos is detrimental to survival, it has been shown that under certain conditions mammalian embryos can survive rapid freezing-thawing. In this study, 237 human fertilized oocytes (93 pronucleates, 20 multipronucleates, and 124 cleaved embryos) were frozen for a period of 1 day to 7 months using the ultrarapid freezing system. After thawing, 94% of the embryos in the pronucleate group and 89.5% in the multipronucleate group showed normal morphological features, and 79% and 71%, respectively, started to cleave. Forty cleaved embryos were also frozen thawed, but only 15 (37.5%) survived at thawing. Thirty-four frozen-thawed cleaved embryos were transferred to 20 patients during spontaneous cycles. Four patients became pregnant. PMID- 2307247 TI - Luteal rescue in in vitro fertilization-embryo transfer. AB - The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization (IVF) program were compared. A control group (group I) consisted of 28 women (28 cycles) who received our standard ovulation induction regimen (no luteal phase support). The treatment group (group II) consisted of 40 women (42 cycles) who were prospectively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin (hCG) 5 days after the initial hCG dose. The groups were matched for age and cause of infertility. Estradiol (E2) and progesterone (P) were measured on the day of embryo transfer and every 3 to 4 days thereafter. Luteal phase hCG support significantly augmented (1) E2 and P levels in the conception cycles of group II compared with group I and (2) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II. An ongoing pregnancy rate of 19% was achieved in group II. This was not statistically different from the 13% ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our standard ovulation induction regimen during the period of the study. In summary, the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG. It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri implantation hormonal milieu. PMID- 2307248 TI - Improved pregnancy rates and outcome with gamete intrafallopian transfer when follicular fluid is used as a sperm capacitation and gamete transfer medium. AB - Follicular fluid (FF) is a dynamic medium rich in steroids, polypeptide hormones, and growth factors. Preovulatory FF can stimulate spermatozoal acrosome reaction. Moreover short preincubation of washed sperm with FF improves sperm performance in the hamster egg penetration assay. In the current study, FF was used to capacitate sperm and as a transfer medium in 131 gamete intrafallopian transfer (GIFT) procedures. Ham's F-10 medium (GIBCO, Grand Island, NY) with 50% maternal serum was used in another 29 GIFT procedures. In the Ham's F-10 group, 29 GIFT procedures were performed in 25 patients with a pregnancy rate of 21% per laparoscopy and 24% per patient. In the FF group, 131 GIFT procedures were performed in 100 patients with a pregnancy rate of 50% per laparoscopy and 66% per patient, with a 59% ongoing pregnancy rate per patient. The most significant improvement was in the male factor group with a pregnancy rate of 0% in the Ham's F-10 group and 44% per procedure in the FF group. We conclude that the use of FF for sperm capacitation and as a gamete transfer medium significantly improves GIFT pregnancy rates and outcome. PMID- 2307249 TI - A prospective randomized study of pregnancy rates following intrauterine and intracervical insemination using frozen donor sperm. AB - Cryopreserved sperm have lowered fertility when compared with fresh sperm in artificial insemination by donor programs. The purpose of this study was to compare pregnancy rates following intrauterine insemination (IUI) and intracervical insemination (ICI) with cryopreserved sperm in a prospective trial using the patient as her own control. A total of 154 patients were randomized into alternating treatment cycles and underwent 238 cycles of IUI and 229 cycles of ICI. The pregnancy rate per treatment cycle was 9.7% following IUI and 3.9% following ICI. Treatment outcome was influenced by patient age, ovulatory status, and endometriosis. Pregnancy success correlated well with the post-thaw survival of sperm and the number of motile cells inseminated. In spite of having normal semen parameters, some donors were found to have markedly reduced sperm fecundity. We conclude that IUI with cryopreserved sperm can be an effective treatment for couples with infertility, genetic indications, or other reasons. PMID- 2307250 TI - Electrophoretical patterns of seminal plasma proteins in patients with cystic fibrosis. AB - Seminal plasma (n = 12) from cystic fibrosis (CF) patients were analyzed by gel electrophoresis using seminal plasma and expressed prostatic secretion from fertile men as controls. Heavy precipitation at the entering position of the gel and streaking in the gel matrix was observed, demonstrating a reduced solubility of seminal proteins in CF. Comparison of the protein patterns evidenced that CF seminal plasma (CF-SP) mainly consisted of prostatic components. Although lactoferrin was undetectable in all samples, trace amounts of low molecular weight proteins were observed in two patients. This latter finding could imply that CF-SP may contain proteolytic fragments of prostatic and/or vesicular proteins or de novo synthesized components. PMID- 2307251 TI - Optimizing the sperm penetration assay with human follicular fluid. AB - Major limitations of the conventional sperm penetration assay are the inability to assess several aspects of sperm function (zona binding and penetration) and the absence of human ovulatory products known to influence fertilization. We therefore modified the sperm penetration assay by the addition of human follicular fluid (FF) to induce the acrosome reaction in an attempt to improve the false-negative rate of the conventional technique. In 26 patients with negative results, results became positive in 20 with human FF and the acrosome reaction increased fourfold. In 19 different men, we compared the results of the conventional and modified assays with outcome of in vitro fertilization. The false-positive rate was the same, but the false-negative rate was reduced from 40% to 7% with the addition of human FF. PMID- 2307252 TI - A survey of the ultrastructural defects associated with absent or impaired human sperm motility. AB - The sperm tails of 400 patients having absent or impaired sperm motility were examined by electron microscopy. A wide variety of fine-structural defects were observed although all of the patients fell into clearly defined groups. Total or partial dynein arm deficiency was observed in 12 patients (3%). Ninety-one patients (23%) had sperm with a spectrum of fine-structural defects, whereas 90 patients (23%) were necrospermic. Subjects with low motility, but with at least a few tails of normal structure, had a 5% pregnancy rate, whereas those patients with similar overall motility, but in whom no normal sperm were seen, produced no pregnancies. The results confirm the importance of making an electron microscopical examination of the sperm of patients with asthenozoospermia. PMID- 2307253 TI - Percutaneous absorption of 17 beta-estradiol in ovariectomized rhesus monkeys: skin and serum pharmacokinetics. AB - The skin and serum kinetics of percutaneous estradiol (E2) gel (Oestrogel; Besins Iscovesco Laboratories, Paris, France) absorption in 11 ovariectomized rhesus monkeys (3 pretreated with diethylstilbestrol [DES]) was studied. The gel (1.5 mg E2) mixed with 7.5 x 10(5) cpm tritiated E2 (3H-E2) was applied to abdominal skin. Serial skin biopsies were taken from the application area and at 1 and 3 cm beyond, as well as from perineum and dorsal skin; and radioactivity measured to estimate tissue levels of E2 derived from percutaneous delivery. Simultaneous femoral serum samples were taken for RIA of E2. Skin 3H-E2 reached a peak at approximately 60 minutes, which was sustained for about 10 hours. Lateral diffusion of the radiolabeled E2 was limited to about 1 cm. Serum E2 levels reached a peak at 60 minutes and remained elevated for 20 hours after a single application. A strong correlation existed between skin and serum E2 levels: r = 0.828. DES did not modify the E2 skin absorption kinetics, but in 2 of 3 monkeys DES reduced the E2 serum levels, suggesting an effect after skin absorption. We conclude that percutaneously delivered E2 manifests a sustained entry into serum. The steady state of continuous release of E2 into circulation derives from a postabsorption skin reservoir of estrogen product. PMID- 2307254 TI - New guidelines for the use of semen donor insemination: 1990. The American Fertility Society. PMID- 2307255 TI - [An inhibitory influence of porcine vasoactive intestinal peptide upon mouse oocyte meiosis in culture]. AB - The germinal vesicle (GV) of follicle-enclosed oocytes in mice remains arrested at the dictyate state of meiosis. Upon releasing the oocytes from the follicles, the meiotic process resumes, leading to dissolution of the GV, suggesting that factors in the follicular constituents sustain the meiotic arrest of oocytes. Vasoactive intestinal peptide (VIP) was demonstrated in the ovary and found to have a wide range of biological effects. In this study, the possibility of VIP to be a factor which induces meiosis-arrest of oocytes was evaluated. Porcine VIP inhibited resumption of meiosis of cumulus-enclosed mouse oocytes in vitro. Germinal vesicle breakdown (GVBD) was prevented in more than 50% of the oocytes treated by VIP at a concentration of 30 microM. The inhibiting effect of VIP was dose-dependent and reversible. Spontaneous resumption of meiosis of isolated oocytes in vitro was reported to be inhibited by dibutyryl cAMP (dbcAMP) added to the medium, indicating that meiotic arrest can be sustained by maintaining intra oocyte cAMP above a critical level. It was further reported that follicular fluid contains substances that maintain meiotic arrest in association with exogenous dbcAMP. In the present study, the blocking activity of dbcAMP for the spontaneous resumption of meiosis was not potentiated by the addition of VIP in the medium. The present results suggest that VIP may play a role in the regulation of resumption of oocyte meiosis, and that VIP is not a substance which maintains meiotic arrest in association with cAMP. PMID- 2307257 TI - [An unusual association of transient resolving thyrotoxicosis due to painless thyroiditis, hypopituitarism and central diabetes insipidus associated with spontaneous pituitary apoplexy]. AB - Pituitary apoplexy is characterized by a wide spectrum of clinical features. A quite rare case of painless thyroiditis, hypopituitarism and central diabetes insipidus (DI) followed by pituitary apoplexy was presented. A 61-year-old woman was admitted to our hospital in May, 1986 because of marked general malaise, polydipsia and weight loss which became progressively worse. Four months earlier she had experienced episodes of abrupt onset of severe headache associated with nausea and blurring vision. Physical examinations revealed a fine tremor, dry skin and nervousness. The thyroid gland was not palpable. Visual fields were intact. Her blood pressure was 105/64 mmHg with variable tachycardia. The routine laboratory studies were normal or negative except for hypoalbuminemia, hypocholesterolemia and hypernatremia. Erythrocyte sedimentation rate was 12 mm/hr. An impairment in corticotropin secretion was suspected from the low plasma cortisol and the low urinary excretion of 17-OHCS and the sufficient response to ACTH. Basal levels of GH and gonadotropin were also low, and responses to the stimulation tests (Insulin-stress, L-DOPA, and LH-RH) were all blunted. Brain computed tomographic scan and magnetic resonance imaging demonstrated a suprasellar mass that, after infusion, developed peripheral ring-like enhancement and large hyperintense pituitary mass, respectively. A diagnosis of pituitary apoplexy with anterior pituitary failure was made. However, the initial levels of thyroid hormones showed elevated as follows: Free T3 7.6 pg/ml, Free T4 3.3 ng/dl and T3-resin uptake 41.1%. TSH responses to TRH were all suppressed. TSH receptor antibody (TBII) was negative. Both antithyroglobulin and antimicrosomal antibodies were repeatedly positive. A thyroid scan with 99mTc revealed no uptake in the thyroid area. These findings led us to the diagnosis of "painless autoimmune thyroiditis". She had become hypothyroid without any medication. At that time radioactive 99mTc and 123I uptakes increased significantly. When hydrocortisone was substituted, daily urine output abruptly increased to about 10 liters with low osmolality, and the presence of DI was suspected. This diagnosis was confirmed by water deprivation and hypertonic saline infusion tests and subsequent pitressin test. She is currently quite well on L-thyroxine, hydrocortisone and desmopressin (1988). This association with pituitary apoplexy must be a rare occurrence, as a literature search has failed to find a similar case. The pathogenetic trigger of "painless thyroiditis" in this case may be responsible for some immunological change due to secondary adrenal insufficiency after pituitary apoplexy. PMID- 2307256 TI - [A comparative study of C19 steroid-induced hypertension and deoxycorticosterone acetate (DOCA)-salt hypertension]. AB - In order to evaluate the hypertensinogenic action of 19-hydroxyandrostenedione (19-OH-AD), which has been reported to be an amplifier of mineralocorticoid, the changes in several humoral factors were observed in 19-OH-AD treated rats as compared to those in DOCA hypertensive rats. Twenty-five male Wistar rats were castrated at 11 weeks of age, and the experiments were begun at 12 weeks of age. The rats were divided into 3 groups. The control group (n = 8) was given an s.c. injection of 0.2 ml of sesame oil. The 19-OH-AD group (n = 10) was injected s.c. with 10 mg of 19-OH-AD dissolved in 0.2 ml of sesame oil, and the DOCA group (n = 8) was injected s.c. with 10 mg of DOCA dissolved in 0.2 ml of sesame oil three time weekly. The urine was collected for a period of 24 hours, and the urine volume, and urinary excretions of electrolytes, prostaglandin E2 (PGE2), kinin and catecholamine were measured before and after the start of the experiment. The systolic blood pressure (S.B.P.) was measured by the tail-cuff method. The S.B.P. values before and at 9 weeks after the start of the experiments were 136.7 +/- 3.8 and 156.0 +/- 2.6 mmHg in the 19-OH-AD group, and 140.6 +/- 5.6 and 179.3 +/- 5.5 mmHg in the DOCA group, respectively. Body weight, which was elevated in both groups, was higher in the 19-OH-AD group than in the DOCA group. Water intake and urine volume were significantly (p less than 0.001) increased only in the DOCA group. The urinary Na/K ratio was significantly (p less than 0.001) elevated in the DOCA group as compared to that in the other two groups. However, there was no significant difference in urinary Na/K ratio between the control and 19-OH-AD groups. The urinary PGE2 and kinin excretions were significantly (p less than 0.01) increased in the DOCA group but did not change appreciably in the 19-OH-AD group. The urinary catecholamine excretion was significantly increased in the DOCA group. However, there were no differences in the catecholamine excretion between the control and 19-OH-AD groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2307258 TI - Identification of [14C]carmoisine metabolites in bacterial suspension of rat faeces. AB - An in vitro system consisting of a bacterial suspension of human or rat faecal microflora brought about the biological reduction of the red azo dye [14C]carmoisine to 1-naphthyl-amine-4-sulphonic acid (NA) and 2-amino-1-naphthol 4-sulphonic acid (ANA). These metabolites have been unequivocally identified by radio-HPLC, spectroscopic methods, dilution with cold authentic standards and evidence that the specific activity of the diluted compounds remained constant throughout repeated crystallization, acetylation and purification. The results clearly indicated that samples derived from anaerobic incubations have to be processed for analysis in the complete absence of oxygen. In the presence of oxygen, the formation of a complex pattern of compounds in addition to NA was observed as a consequence of the chemical decomposition of ANA. PMID- 2307259 TI - The aluminium content of infant formula and tea. AB - Tea and infant formulae have been examined for the presence of aluminium. Concentrations in 13 different tea infusions ranged from 2.2 mg/l to 4.5 mg/l. In cow's milk-based infant formulae as made up for consumption, aluminium levels of between 0.03 mg/l and 0.20 mg/l were detected. Higher amounts were present in soya-based formulae with concentrations ranging from 0.64 mg/l to 1.34 mg/l. PMID- 2307260 TI - Isotope ratio and isotope dilution analysis of lead in wine by inductively coupled plasma-mass spectrometry. AB - The lead content of 12 wine samples was measured by inductively coupled plasma mass spectrometry using the methods of standard addition and isotopic dilution analysis. An additional wine sample was analysed by external calibration, standard addition and isotopic dilution analysis. The lead content of the wine samples was in the range 30-150 ng ml-1 and good agreement between the different techniques was observed. Analysis of lead isotope ratios revealed significant differences between Australian and European wines, reflecting the different isotopic composition of Australian lead. PMID- 2307261 TI - Determination of residues of deltamethrin in milk and butter. AB - A method is described for the determination of deltamethrin, particularly in mild and dairy products. Residues and fat were co-extracted with acetone and light petroleum, partitioned with acetonitrile-methylene chloride and centrifuged (-10 degrees C). The extract was purified by gel permeation chromatography. A Florisil clean-up method was tested but did not seem effective enough. Analysis was performed by gas-liquid chromatography with a 63Ni electron-capture detector on 3% SE-30 using a short column (40 cm). Confirmation was effected by gas chromatography-mass spectrometry with an SE-30 capillary column (10 m). Recoveries from fortified samples ranged from 72 to 88% for milk spiked with 0.06 ppm and butter spiked with 2 ppm and was 94% for milk spiked with 0.016 ppm of deltamethrin. PMID- 2307262 TI - Release of formaldehyde and melamine from tableware made of melamine-formaldehyde resin. AB - The relationship between the concentrations of formaldehyde and melamine released into 4% acetic acid from dishes and bowls made of melamine-formaldehyde resin was determined. The average concentrations in the migration solution after the sample had been treated at 60, 80, and 95 degrees C for 30 min with 4% acetic acid were 0.0 +/- 0.1, 0.5 +/- 0.4 and 3.0 +/- 2.2 ppm, respectively for formaldehyde and 0.04 +/- 0.07, 0.21 +/- 0.20 and 1.19 +/- 1.18 ppm, respectively for melamine. The correlation between the concentrations of formaldehyde and melamine released at 95 degrees C was y=0.4858x-0.2728 (r=0.8860), where y is melamine concentration (ppm), x is formaldehyde concentration (ppm) and r is the correlation coefficient. The molar concentration ratios of formaldehyde to melamine (F/M ratio) were 15.4 +/- 11.6 at 80 degrees C and 14.9 +/- 10.1 at 95 degrees C. Hence the release of both migrants was affected by temperature but the F/M ratio was not affected. The release of both compounds was was increased on repetition of the migration test at 95 degrees C but their concentrations remained constant after the tenth and seventeenth repetitions of the treatment. During this period, the F/M ratio decreased according to the equation 1n y= 1.4344 1n x+3.7814 (r=-0.9984) for a sample before the tenth repetition of the treatment and remained between 1.7 and 1.9 after the twelfth repetition, where y is the F/M ratio and x is the number of repetitions of the treatment. PMID- 2307263 TI - Migration of epoxidised soya bean oil into foods from retail packaging materials and from plasticised PVC film used in the home. AB - Epoxidised soya bean oil (ESBO) is used as a plasticiser and heat stabiliser in a number of feed contact materials, in particular in poly(vinyl chloride) (PVC) films and gaskets. The level of ESBO migration into foods has been determined using a combined gas chromatographic/mass spectrometric (GC/MS) analytical procedure. The study has included both the use of ESBO-containing materials for retail packaged foods and the domestic use of plasticised PVC films for applications such as wrapping food and covering food for re-heating in a microwave oven. Levels of ESBO in fresh retail meat samples wrapped in film ranged from less than 1 to 4 mg/kg, but were higher (max. 22 mg/kg) in retail cooked meat. Migration into sandwiches and rolls from 'take-away' outlets ranged from less than 1 to 27 mg/kg depending on factors such as the type of filling and the length of the contact time prior to analysis. The levels of migration of ESBO into cheese and cakes were consistent with previous experience with plasticiser migration--direct contact with fatty surfaces leading to the highest levels. When the film was used for microwave cooking in direct contact with food, levels of ESBO from 5 to 85 mg/kg were observed, whereas when the film was employed only as a splash cover for re-heating foods, ESBO levels ranged from 0.1 to 16 mg/kg. For a variety of baby foods there was no significant difference in ESBO levels between foods packaged in glass jars with PVC gaskets and foods in cans containing ESBO in the can lacquer. In both cases ESBO levels were low, ranging from less than 0.1 to 7.6 mg/kg. It is not clear for these retail samples, if the low levels observed (average 1.9 mg/kg) result solely from migration or contain some contribution from naturally occurring epoxides. PMID- 2307264 TI - Effect of cooking on availability and in vitro nitrosation of precursors of volatile N-nitroso compounds in seafood. AB - Aqueous extracts of uncooked and cooked samples of squid and shrimp, characterized by their high amine content, were exposed to nitrate. The samples were cooked following traditional Italian recipes: stewing, grilling and deep frying for squid; boiling, grilling and deep-frying for shrimp. Incubation of the aqueous extracts with nitrite in acidic medium yielded appreciable amounts of N nitrosodimethylamine. Ascorbic acid and alpha-tocopherol were effective in preventing nitrosation of seafood amines only in the presence of molar excesses of these vitamins. An attempt at modulating nitrosation through the use of food ingredients naturally rich in vitamin C was unsuccessful. PMID- 2307265 TI - Assay of N-nitrosamines in foodstuffs produced in the USSR by gas-liquid chromatography with a thermal energy analyser. AB - The content of volatile N-nitrosamines in over 4000 samples of domestic foodstuffs of plant and animal origin were studied. It was found that 88% of the samples studied contained N-nitrosamines, the greatest amounts being detected in some samples of malt and beer, fish products and some meat products. The impact of food processing technologies on the formation of N-nitrosamines is discussed. Possibilities of preventing the accumulation of N-nitrosamines during the process of food production are discussed. PMID- 2307266 TI - Volatile nitrosamines in microwave-cooked bacon. AB - Bacon was analysed for volatile nitrosamines after microwave cooking, and the results were compared with those obtained after frying bacon in a pan. Microwave cooking gave statistically significantly lower levels of all three volatile nitrosamines detected in the bacon. NPYR was found in all 20 samples fried in a pan, but in only five microwave-cooked samples. The average volatile nitrosamine levels (micrograms/kg) in microwave-cooked bacon and pan-fried bacon were: NDMA, 0.3 and 1.2; NPIP, 0.04 and 0.2; NPYR, 0.1 and 4.5. PMID- 2307267 TI - Incidence of mycotoxins in maize grains in Bihar State, India. AB - A regular survey of some maize-growing areas of Bihar state, India, for three consecutive years (September 1984 to September 1986) revealed heavy infestations of mycotoxin-producing fungi with different maize samples. Aflatoxin-producing fungi had the highest frequency of occurrence in all the cases and aflatoxins were the most common mycotoxins elaborated by these fungi. Maize samples of the Kharif crop had a greater incidence of aflatoxins (47%) than the samples of rabi crop (17%). Stored maize grains also had a high incidence of aflatoxins (43%). Most of the contaminated samples contained aflatoxins at levels above 20 micrograms/kg. PMID- 2307268 TI - Effect of ammoniation on the carcinogenicity of aflatoxin-contaminated groundnut oil cakes: long-term feeding study in the rat. AB - The efficacy of detoxication by ammoniation of aflatoxin-contaminated groundnut oil cakes was determined in long-term (18 months) feeding experiments with rats. The aflatoxin content of the cake was reduced very considerably by the pressurized application of ammonia, dropping from 1000 to 140 ppb at a gas pressure of 2 bar and to 60 ppb at 3 bar. No reversion was noted during the experiment. The percentage of hepatic tumours obtained was very high for the untreated cakes, but fell sharply with medium treatment and was reduced to zero by the treatment at 3 bar. A satisfactory dose-effect relationship was shown between the residual aflatoxin content of the cakes and the observed incidence of tumours. The results show that ammonia treatment is a practical solution to the problem of the carcinogenic potency of contaminated oil cakes. PMID- 2307269 TI - Determination of ivermectin residues in swine tissues--an improved clean-up procedure using solid-phase extraction. AB - A rapid and sensitive HPLC method has been developed for the determination of ivermectin in swine tissues. The clean-up procedure is based on solid-phase extraction on a Bond-Elut C8 cartridge. The average recovery from spiked swine muscle tissue was 87% in the concentration range 2-20 micrograms/kg. The method has a limit of detection of 0.5-1 microgram/kg. A survey of the levels in muscle tissues from 35 sanitary slaughtered sows was made. Five samples were found to contain ivermectin at concentrations between 3.4 and 27.6 micrograms/kg. A good correlation (r = 0.9696) was found between these results and those obtained using another established method. PMID- 2307270 TI - Cadmium and lead in muscle tissue and organs of broilers, turkeys and spent hens and in mechanically deboned poultry meat. AB - Cadmium and lead levels have been determined in meat, livers and kidneys of turkeys, in livers and kidneys of spent hens, in kidneys of broilers and in mechanically deboned poultry meat (MDPM), by dry ashing of the sample with Mg(NO3)2 followed by differential pulse anodic stripping voltammetric analysis. The possible age-dependent cadmium and lead accumulation in livers and kidneys of turkeys was also studied. The cadmium concentrations in meat and organs of poultry are in good agreement with data reported for other countries, but lead concentrations were low compared with most data reported in the literature. The cadmium levels in kidneys and livers of turkeys increased with age, whilst the lead concentrations were unrelated to age. The cadmium and lead concentrations in industrially prepared MDPM from broiler carcasses were very low (less than 0.001 0.004 mg/kg and less than 0.01-0.06 mg/kg, respectively). In MDPM prepared from backs (including the kidneys) and necks, elevated cadmium concentrations were found. The increase was related to the cadmium concentrations in the kidneys. In MDPM prepared from broilers, turkeys and spent hens the cadmium concentrations varied between 0.001 and 0.002 mg/kg, 0.005 and 0.006 mg/kg and 0.007 and 0.028 mg/kg, respectively. For lead the concentrations in meat and MDPM were similar. It can be concluded from the results that in MDPM prepared from spent hens and possibly turkeys, when incorporating the kidneys, cadmium concentrations greater than 0.05 mg/kg, (the legal limit for cadmium in poultry meat in The Netherlands) may occur. PMID- 2307271 TI - The effects of dietary methylcellulose in man. AB - Following a 7-day control period, five male volunteers consumed, on each of 23 consecutive days, a weight of methylcellulose (MC) equal to ten times the acceptable daily intake (25 mg/kg b.w.) approved by the EEC and the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The MC was well tolerated; no allergic responses were reported. Measurements before and at the end of the test period showed that the ingestion of MC, as a pre-hydrated gel, acted as a bulking agent in terms of increased faecal wet (p less than 0.05) and dry weight, with intestinal transit time increasing for three but decreasing for two of the volunteers. Small changes, well within the normal ranges, occurred in some haematological indices, serum lipids and a few plasma biochemistry parameters. There were no changes in urinalysis parameters or breath hydrogen concentrations. There were small (p less than 0.05) reductions in faecal volatile fatty acids and neutral sterols (mumol/g dry weight). The decreases in blood glucose and plasma insulin after 60 min were also within the normal clinical range. The data provide no indications of any adverse effects of methylcellulose resulting from its ingestion for 23 days at the level of 250 mg/kg b.w. PMID- 2307272 TI - Lead in alcoholic beverages: a second survey. AB - Results are presented of a survey of lead in beers and wines. Evidence of low level lead contamination of draught beer was found in an earlier survey conducted previously but remedial action initiated by the Brewers' Society has apparently been successful in reducing this contamination. The position in respect of lead contamination of wine is less satisfactory. Wine poured from bottles which have been fitted with tin-coated lead closures may sometimes become contaminated by deposits of lead salts produced by corrosion of the lead closure. Results of a survey of wines from lead-capped bottles show that for bottles sampled during 1985/1986 the lead concentration in 20 out of 100 samples exceeded 1000 micrograms/l (equivalent to the statutory limit for lead in wine of 1 mg/kg as sold). Such contamination could give rise to undesirably high intakes of lead. Action being taken to reduce exposure from this source is described. PMID- 2307273 TI - Kaposi's sarcoma: retrospective study of 67 cases with the classical form. AB - The records of 67 Israeli patients with classical Kaposi's sarcoma treated at Rambam Medical Center were analyzed retrospectively for clinical and laboratory data. As expected, all except 1 patient were of Jewish origin. There was a male predominance with a ratio of 2.2:1. The age of onset was mostly during the 5th to 7th decades of life. The course of the disease was usually slow and indolent. As has been already noted, we found a higher frequency of diabetes mellitus (16.4%). Although a high frequency of second primary malignancy was seen in our patients, this was less so than that described in an American series, 15% as compared to 37%, respectively. The most frequent second malignancy was that of the lymphoreticular system. No serologic evidence for an association with types of herpes virus infection has been found. No alterations in humoral and cellular immunity were demonstrated. These data show similar clinical findings with those described in other series, besides the lower frequency of a second primary malignancy. Some discordance with that described before concerning the relationship with cytomegalovirus infection and T cells subsets was also noted. PMID- 2307274 TI - Properties of acid phosphatase in human stratum corneum. AB - Sheets of stratum corneum were prepared by a trypsinization procedure from human skin samples, homogenized with a freeze press and then fractionated into a soluble fraction and a sediment by centrifugation at 50,000 g. Acid phosphatase (AcP) activity was found in both fractions but the bulk of the activity was detected in the supernatant. Highest activities were observed after treatment with Triton X-100. The bulk of the AcP activity remained bound to the pellet, if suspension and fractionation of the homogenized stratum corneum were performed in acetate buffer in the range between pH 4.0-5.0, probably due to ionic or hydrophobic interactions. AcP activity was totally lost if homogenates or fractions were stored frozen at -20 degrees C in buffers with pH values lower than 4.0. Triton X-100 extracts from whole skin, epidermis, stratum corneum, cultured skin fibroblasts and leukocytes were compared by isoelectric focusing. Extracts from whole skin, epidermis and stratum corneum yielded almost identical patterns with one main AcP activity band at pI of 5.65, whereas a second pronounced band from whole skin behaved similarly to one band from cultured skin fibroblasts and leukocytes (pI 6.1). The prominent band from extracts of stratum corneum and epidermis was not observed in extracts of skin fibroblasts and leukocytes. Hence, we conclude that stratum corneum and epidermis contain a tissue-specific AcP. PMID- 2307275 TI - Percutaneous absorption of zinc from zinc oxide applied topically to intact skin in man. AB - The penetration of zinc through normal skin treated with a zinc oxide (25%) medicated occlusive dressing was studied. The mean release rate of zinc to the skin was 5 micrograms/cm2/h. After 48 h of treatment suction blisters were raised by the "Kiistala method." The zinc concentration of the epidermis, blister fluid and dermis was increased beneath the zinc dressing compared to control-treated skin. The study shows that zinc permeates intact human skin from topically applied zinc oxide in vivo. PMID- 2307276 TI - Desmoplastic trichoepithelioma nosology. Reappraisal about a case developed on a varicella scar. AB - We report the case of a 51-year-old woman who presented with a progressive elevation of the border of an old varicella scar. The lesion which was clinically diagnosed as a basal cell carcinoma turned out to be a typical desmoplastic trichoepithelioma. The development of desmoplastic trichoepithelioma in an area of scarring has not been previously reported. The nosology of this tumor is discussed with particular emphasis on its possible relationship to morphoeic basal cell carcinoma, thus questioning it as a true tumor sui generis. PMID- 2307277 TI - Factor-XIIIa-positive dendrocytes and the dermal microvascular unit. AB - We present an immunohistochemical study with factor XIIIa antibody performed in a variety of cutaneous diseases. Our observations suggest that factor-XIIIa positive dendrocytes, in noninflammatory conditions, may be resident phagocytic cells intimately associated with the microvascular units of the skin. PMID- 2307278 TI - Creatine kinase values during isotretinoin treatment. PMID- 2307279 TI - Psoriasis and atopy. PMID- 2307280 TI - Diseased skin models in the hairless guinea pig: in vivo percutaneous absorption. AB - We observed hydrocortisone and benzoic acid absorption in relation to experimentally induced in vivo damaged skin models in the hairless guinea pig. Radioactivity of the drugs in urine was calculated as absorbed dose. Both drugs have different patterns of excretion in urine. Damaging the skin abolished some barrier function and increased the absorption of both model drugs. With cellophane-tape-stripped skin, the absorption was increased 3 times and 2 times for each drug, respectively. Irritation with 2% sodium lauryl sulfate increased absorption by a ratio of 2-4 times. Defatting with chloroform/methanol (2:1) mixture increased absorption to the greatest extent (5- and 2.7-fold). The possible mechanism of a delipidization effect was considered in view of a visible skin lesion and inflammatory reaction. Precautions are proposed for those with damaged/diseased skin in dealing with topical medications or handling solvents. PMID- 2307281 TI - Induction of target-directed optic axon outgrowth: effect of retinae transplanted to anophthalmic mice. AB - In previous work using neural transplants (Hankin and Lund, 1987) we demonstrated two basic components of optic axon outgrowth in the mammalian retinotectal system: one category of outgrowth utilizes the subpial margin of the rostral brain stem as a preferential substrate (as do normal retinotectal axons); the other type of outgrowth, from retinae embedded deep within the midbrain parenchyma, is distance-dependent and highly target-oriented, but shows little apparent substrate specificity. One explanation for this directed outgrowth is that it is in response to a diffusible factor emanating from cells in the superior colliculus. In the present study we use congenitally anophthalmic mice as recipients for retinal transplants to test whether prior optic innervation of the superior colliculus plays a role in establishing either component of outgrowth. We show that outgrowth along the subpial pathway from a graft placed on the surface of the brain stem can take place in the absence of prior innervation of the superior colliculus. The target-directed outgrowth exhibited by embedded grafts only occurs if the tectum is also innervated by a second graft placed on the surface of the brain stem. It is proposed that tectal cells produce a factor in response to optic innervation and that this directs the growth patterns of embedded grafts. This suggests that optic innervation is a necessary prerequisite for the superior colliculus to produce the proposed diffusible chemotropic signal. In normal development such a factor could function to improve the efficiency of target-finding by later growing optic axons, but it might serve a quite different role, encouraging branching and trophic maintenance of the optic pathway once it has reached the tectum. PMID- 2307282 TI - Enzymatic and envelope-converting activities of pars recta oviductal fluid from Xenopus laevis. AB - Conversion of the coelomic egg envelope to the vitelline envelope of the Xenopus laevis egg is known to take place in the pars recta (PR) region of the oviduct. A method for collecting fluid generated from PR cultured in vitro was devised which enhanced the recovery of envelope-converting factors. By the criteria of melting temperature analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, 125I labeling, ferritin binding, and in vitro fertilization assays, the secretions collected from PR cultured in vitro were capable of modifying the envelope in a manner analogous to that which occurred in vivo, including the limited hydrolysis of one envelope glycoprotein. Hydrolytic activities present in PR fluid were assayed with a number of peptide and carbohydrate substrates. Enzymes which hydrolyzed t-butyloxycarbonyl-Leu-Ser-Thr-Arg-methylcoumarylamide, t-butyloxycarbonyl-Phe-Ser-Arg-methylcoumarylamide, and t-butyloxycarbonyl-Val Leu-Lys-methylcoumarylamide were found to be present in PR fluid at levels elevated by threefold or more over amounts found in a comparable volume of blood plasma. PMID- 2307283 TI - Regulation of carbon flux from amino acids into sugar phosphates in Xenopus embryos. AB - Xenopus laevis oocytes and embryos are glycogenic cells, metabolizing sugar phosphates into glycogen. These cells have very low pyruvate kinase activity in vivo and, consequently, make little pyruvate and lactate through glycolysis. Nevertheless, oocytes and embryos do contain significant pyruvate and lactate levels. To determine the source of carbon for sugar phosphates and pyruvate, 14C labeled intermediary metabolites were injected into fertilized eggs and their metabolism examined by thin-layer chromatography. Alanine, pyruvate, and lactate form a pool of carbon that fluxes into sugar phosphates. Cytosolic (nonmitochondrial) aspartate, oxaloacetate, and malate form a pool of carbon which is largely blocked in the short-term from entering the smaller alanine/pyruvate/lactate pool. The data indicate that the major source of carbon for sugar phosphates in fertilized eggs and rapidly cleaving embryos is the alanine/pyruvate/lactate pool. Pyruvate from this pool is converted in the mitochondria to phosphoenolpyruvate, which in turn is metabolized outside the mitochondria to sugar phosphates. A key enzyme in regulating flux from amino acid carbon to pyruvate is malic enzyme. Three malic enzyme isozymes, one soluble and two mitochondrial, were partially isolated and kinetically characterized from total ovarian tissue. Full-grown oocytes and eggs, however, have very low soluble malic enzyme activity, which results in the separation of the cytosolic aspartate/oxaloacetate/malate and alanine/pyruvate/lactate pools. PMID- 2307284 TI - The "lecithotrophic" sea urchin Heliocidaris erythrogramma lacks typical yolk platelets and yolk glycoproteins. AB - The sea urchin Heliocidaris tuberculata undergoes typical development, forming an echinoid pluteus larva, whereas H. erythrogramma undergoes direct development via a highly modified, nonfeeding larva. Using a polyclonal antibody prepared against yolk glycoproteins from the typical developer Stronglyocentrotus purpuratus, we found that H. tuberculata contains cross-reactive proteins in abundance, but H. erythrogramma does not. In addition, we used immunoelectron microscopy to demonstrate that unfertilized eggs of H. tuberculata contain yolk platelets, but those of H. erythrogramma do not. PMID- 2307286 TI - Terminal differentiation of head- and foot-specific epithelial cells occurs at the same location in Hydra tissue without polarity. AB - The reappearance of terminally differentiated ectodermal epithelial cells was studied in reaggregates of Hydra cells. These cells first occur separated from undifferentiated gastral tissue in mixed clusters consisting of cells which in normal animals are restricted to opposite body poles. Tentacles containing foot specific basal disc cells as well as feet containing head-specific battery cells were formed from these clusters. This indicates that a positive cross-reaction of head- and foot-forming mechanisms exists at the cellular level and that induction of terminal differentiation precedes the establishment of polarity. PMID- 2307285 TI - Changes in voltage-dependent currents and membrane area during maturation of starfish oocytes: species differences and similarities. AB - Full grown starfish oocytes are arrested at meiotic prophase I in the ovary. The natural hormone 1-methyladenine triggers oocyte maturation which involves meiosis reinitiation along with a variety of morphological, biochemical, and electrical changes. In studying oocytes of two species, Henricia leviuscula and Asterina miniata, using the voltage-clamp technique, we found interesting differences and similarities in the electrophysiological changes which occurred during maturation. Oocytes of both species have three major voltage-dependent currents: an inward Ca2+ current, an inwardly rectifying K+ current, and a transient outward K+ current (A-current). The Ca2+ current and the A-current were similar in the two species but the inward rectifier in Henricia had activation kinetics that were more than 10-fold slower than in Asterina. Nonetheless, all three currents were affected similarly during maturation: the inward Ca2+ currents remained constant in both species, while the two K+ currents decreased in amplitude. In Henricia the membrane surface area decreased substantially during maturation, while in Asterina it remained constant. This may be explained by the more highly infolded state of the membrane in the immature Henricia oocyte. The selective loss of K+ current followed the time course of the area decrease in Henricia, but the same percentage decrease in current occurred in Asterina without a net membrane loss. PMID- 2307287 TI - The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. AB - Mutations in the genes ced-3 and ced-4 prevent almost all of the programmed cell deaths that occur during Caenorhabditis elegans development. To determine the sites of action of these two genes, we performed genetic mosaic analyses. We generated C. elegans animals that carried a free chromosomal duplication bearing either ced-3(+) or ced-4(+) in an otherwise homozygous ced-3 or ced-4 genetic background. We used other genes on the duplication as markers to identify genetic mosaic animals in which the duplication was present in some but not all cells. The patterns of cell death survivors in these mosaic animals indicated that the products of both ced-3 and ced-4 function within dying cells to cause cell death. PMID- 2307288 TI - Effects of beta-D-xyloside on differentiation of the respiratory epithelium in the fetal mouse lung. AB - Differentiation of respiratory endings in the fetal lung appears to be controlled by its surrounding mesodermal capsule. The capsule may exert its influence by controlling the composition of the epithelial basal lamina or of the extended extracellular matrix that is deposited during the period when alveolar sacs are formed. As a first step in testing this hypothesis, the effects of the drug, rho nitrophenyl-beta-D- xylopyranoside (beta-xyloside), an inhibitor of proteoglycan synthesis, and its inactive alpha anomer (alpha-xyloside) were examined. Lung primordia from mice at 16 days of gestation were tested for inhibition of morphological and functional differentiation as a result of drug treatment. Pseudoglandular lung epithelium did not form respiratory endings, contained fewer specialized cells, and accumulated little additional surfactant when treated with beta-xyloside but developed normally when treated with alpha-xyloside or grown in control medium. The results are interpreted to suggest that deposition of an extracellular matrix rich in proteoglycan is required to support maturation of the respiratory epithelium. PMID- 2307289 TI - Immunoelectron microscopy of type X collagen: supramolecular forms within embryonic chick cartilage. AB - To determine the supramolecular forms in which avian type X collagen molecules assemble within the matrix of hypertrophic cartilage, we performed immunoelectron microscopy with colloidal gold-labeled monoclonal antibodies. In addition double labeled analyses were performed for the molecule and type II collagen, employing two monoclonal antibodies attached to different size gold particles. Both in situ limb cartilages and the extracellular matrix of chondrocyte cultures were examined. We observed in both systems that the type X collagen is present in two forms. One is as fine filaments (less than 5 nm in diameter) within mats which are found predominantly in the pericellular matrix of the hypertrophic chondrocytes. The second form is in association with the fibrils (10-20 nm in diameter) which also react with the antibody for type II collagen. It seems that the filamentous mats represent a form in which the type X collagen is initially secreted from the cell. The type X associated with the striated fibrils most likely represents a secondary association of the molecule with preexisting type II/IX/XI fibrils. The data are consistent with our previously proposed hypothesis that type X collagen is involved in, and perhaps even "targets," certain matrix components for degradation and removal. PMID- 2307290 TI - Spatial and temporal patterns of interstitial cell migration in Hydra vulgaris. AB - Interstitial cell migration was characterized in Hydra vulgaris (formerly H. attenuata) and the effects of axial position and tissue injury on migration were investigated. Migrating cells were labeled with the thymidine analog, bromodeoxyuridine, and grafted into unlabeled host polyps. Alternatively, cells were labeled directly in hosts with the fluorescent, carbocyanine dye, DiI. The results show that cell migration appeared constrained to proximal (toward the basal disk) or distal (toward the tentacles) movements, but were never lateral. Some cells moved bidirectionally. The fastest migrating cells moved an average of 28 microns/hr. Two to six percent of the gastric region interstitial cells migrated in 1 day and accumulated throughout the body column. In grafted polyps, an average of eight cells emigrated from midgastric regions every hour. Tissue injury had no observed effect on the amount of cell migration. Cells emigrating from midgastric regions showed a preference for distal accumulation, and this bias was enhanced when migrating cells originated from more distal positions in the polyp. Proximally derived tissue grafted to a more distal position also showed similar, preferential distal migration, indicating that interstitial cell migration patterns are dependent upon their position in the body column and not upon their origin. Migrating interstitial cells are slower moving and less numerous than migrating nematocytes in H. vulgaris, but since their migration patterns are similar, the migration of both cell types may be influenced by the same directional cues. PMID- 2307291 TI - Morphallaxis in an aquatic oligochaete, Lumbriculus variegatus: reorganization of escape reflexes in regenerating body fragments. AB - We describe functional and anatomical correlates of the reorganization of giant nerve fiber-mediated escape reflexes in body fragments of an aquatic oligochaete, Lumbriculus variegatus, a species that reproduces asexually by fragmentation. Since fragments from any axial position always regenerate short heads (seven or eight segments long) and much longer tail sections, segments originating from posterior fragments become transposed along the longitudinal axis and acquire, by morphallaxis, features of escape reflex organization that conform to their new anterior position. Using noninvasive electrophysiological recordings we have quantified, on a day-to-day and a segment-by-segment basis, the reorganization that occurs in sensory field arrangements of the medial (MGF) and lateral (LGF) giant nerve fibers, as well as changes in giant fiber conduction velocity and morphometry. Our results show that (1) posterior fragments, originally subserved by the LGF sensory field gradually become subserved by the MGF sensory field; (2) appropriate increases in the ratio of MGF:LGF cross-sectional area, perimeter, and conduction velocity accompany the reorganization in giant fiber sensory fields; and (3) sensory field reorganization can be repeatedly reversed by additional amputations. These results demonstrate that the functional organization of escape reflexes is highly plastic and that morphallaxis may result from the counterbalance of morphogenic influences localized within the anterior and posterior ends of regenerating body fragments. PMID- 2307292 TI - Effects of maternal diabetes on placental transfer of glucose in rats. AB - In situ perfusion of the fetal side of the anesthetized rat placenta was used to monitor glucose fluxes in nondiabetic, streptozocin-induced diabetic (STZ-D), acutely hyperglycemic nondiabetic, and acutely normoglycemic STZ-D rats. STZ-D resulted in increased accumulation of glucose in the perfusate during a single passage through the fetal vasculature compared with nondiabetic rats, and this increase was maintained in normoglycemic STZ-D rats, indicating glucose release from placental stores. The fractional clearance of 3-O-[14C]methylglucose, a nonmetabolizable glucose analogue, across the placenta was decreased in both STZ D groups compared with nondiabetic rats but unchanged in hyperglycemic nondiabetic rats, implying a reduction in glucose transporters in diabetic placentas. The difference between the transfer of D-[3H]glucose and 3-O [14C]methylglucose indicated that 17% of the glucose was retained while traversing the placenta of nondiabetic rats, whereas a smaller percentage (8%) but a larger absolute amount (9 vs. 6 mumol/h) of glucose was retained by the placentas of the severely STZ-D rats. This retention was markedly enhanced in hyperglycemic nondiabetic rats and STZ-D rats when rendered normoglycemic. The net accumulation of perfusate glucose was less than that predicted from radiolabeled transfer data, indicating that glucose is also back transferred from the perfusate to the mother's placenta. We conclude that maternal diabetes markedly affects placental glucose flux. PMID- 2307293 TI - Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol. AB - To assess the potential of myo-inositol-supplemented diets to prevent diabetes induced vascular functional changes, we examined the effects of diets supplemented with 0.5, 1, or 2% myo-inositol on blood flow and vascular filtration function in nondiabetic control rats and rats with streptozocin induced diabetes (STZ-D). After 1 mo of diabetes and dietary myo-inositol supplementation, 1) 131I-labeled bovine serum albumin (BSA) permeation of vessels was assessed in multiple tissues, 2) glomerular filtration rate (GFR) was estimated as renal plasma clearance of 57Co-labeled EDTA, 3) regional blood flows were measured with 15-microns 85Sr-labeled microspheres, and 4) endogenous albumin and IgG urinary excretion rates were quantified by radial immunodiffusion assay. In STZ-D rats, 131I-BSA tissue clearance increased significantly (2- to 4 fold) in the anterior uvea, choroid-sclera, retina, sciatic nerve, aorta, new granulation tissue, diaphragm, and kidney but was unchanged in skin, forelimb muscle, and heart. myo-Inositol-supplemented diets reduced diabetes-induced increases in 131I-BSA clearance (in a dose-dependent manner) in all tissues; however, only in new granulation tissue and diaphragm did the 2% myo-inositol diet completely normalize vascular albumin permeation. Diabetes-induced increases in GFR and in urinary albumin and IgG excretion were also substantially reduced or normalized by dietary myo-inositol supplements. Increased blood flow in anterior uvea, choroid-sclera, kidney, new granulation tissue, and skeletal muscle in STZ-D rats also was substantially reduced or normalized by the 2% myo inositol diet. myo-Inositol had minimal if any effects on the above parameters in control rats. These observations indicate that diabetes-induced increases in regional blood flow, 131I-BSA permeation, GFR, and urinary protein excretion can be markedly reduced or normalized by consumption of myo-inositol-supplemented diets that raise plasma myo-inositol levels approximately fivefold. The failure of the 2% myo-inositol diet to normalize GFR and blood flow and albumin permeation in several tissues despite markedly elevated plasma myo-inositol levels and normal or elevated tissue myo-inositol levels indicates that if vascular functional changes in these tissues are linked to altered myo-inositol levels, they are resistant to normalization by elevation of plasma myo-inositol levels. These results suggest that other factors independent of changes in relative or absolute tissue myo-inositol levels may play an important role in the pathogenesis of diabetes-induced vascular functional changes in these tissues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2307294 TI - Diabetes-related changes in chromatin structure of brain, liver, and intestinal epithelium. AB - To determine whether diabetes alters chromatin structure in vivo, fluorometric analysis of alkali-induced DNA unwinding was carried out in various tissues of streptozocin-induced diabetic rats and genetically obese diabetic (db/db) mice. When zero-order kinetics were used to analyze the data, the percentage of double stranded DNA (%dsDNA) unwinding in brain, liver, and intestinal epithelium of diabetic rats maintained for 4 wk was significantly reduced compared with vehicle injected control rats (%dsDNA 0.37 +/- 0.05 vs. 0.73 +/- 0.02 for brain, 0.59 +/- 0.1 vs. 0.84 +/- 0.02 for liver, and 0.58 +/- 0.07 vs. 0.90 +/- 0.13 for intestinal epithelium). Insulin treatment of diabetic rats normalized the rate of DNA unwinding in liver (0.82 +/- 0.09 %dsDNA/min) and intestinal epithelium (1.05 +/- 0.09 %dsDNA/min), but the increase in the unwinding rate of brain DNA (0.51 +/- 0.06 %dsDNA/min) did not achieve control values. Similarly, alkali-induced DNA unwinding was significantly slower in brain and liver of db/db mice compared with homozygote controls. When first-order kinetics were used to analyze the data, fractional rate constants of DNA unwinding in brain and liver of diabetic rats or mice were significantly smaller than observed in nondiabetic control animals. The fractional rate constant of DNA unwinding in intestinal epithelium was not altered with diabetes. We conclude that chronic uncontrolled hyperglycemia can alter chromatin structure in vivo. PMID- 2307295 TI - Operation of Randle's cycle in patients with NIDDM. AB - It has been suggested that the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) may be caused by substrate competition between glucose and free fatty acids (FFAs) (Randle's cycle). We measured substrate oxidation and energy metabolism in 10 nonobese untreated NIDDM patients with fasting glucose levels of 7-8 mM with indirect calorimetry in the basal state and during an isoglycemic-hyperinsulinemic (approximately 100 mU/L) clamp without (control) and with a concomitant infusion (approximately 0.35 mmol/min) of Intralipid, a triglyceride emulsion. In the control study, fasting rates of total glucose turnover [( 3-3H]glucose) and glucose and lipid oxidation (9.4 +/- 1.4, 7.3 +/- 1.3, and 3.0 +/- 0.4 mumol.kg-1.min-1, respectively) were comparable with those of nondiabetic individuals. After insulin administration, lipid oxidation was normally suppressed (to 1.3 +/- 0.3 mumol.kg-1.min-1, P less than 0.01), as were the circulating levels of FFA, glycerol, and beta-hydroxybutyrate, whereas glucose oxidation doubled (14.1 +/- 1.8 mumol.kg-1.min-1, P less than 0.01). Because glycemia was clamped at 7.5 mM, endogenous glucose production (EGP) was completely suppressed, and total glucose disposal was stimulated (to 25.7 +/- 5.2 mumol.kg-1.min-1, P less than 0.01 vs. baseline), but glucose clearance (3.6 +/- 0.8 ml.kg-1.min-1) was 30% reduced compared with normal. With concomitant lipid infusion, FFA, glycerol, and beta-hydroxybutyrate all rose during the clamp; correspondingly, lipid oxidation was maintained at fasting rates (3.6 +/- 0.2 mumol.kg-1.min-1, P less than 0.01 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307296 TI - High prevalence of NIDDM and impaired glucose tolerance in Indian, Creole, and Chinese Mauritians. Mauritius Noncommunicable Disease Study Group. AB - Mauritius, a multiethnic island nation in the southwestern Indian Ocean, has one of the world's highest diabetes mortality rates. The prevalence of both impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) was investigated in 5080 Muslim and Hindu Indian, Creole (mixed African, European, and Indian origin), and Chinese Mauritian adults aged 25-74 yr who were selected by random cluster sampling. Based on a 75-g oral glucose tolerance test and World Health Organization criteria, the age-standardized prevalence of IGT was significantly greater in women (19.7%, 95% confidence interval [CI] 18.1-21.2) than in men (11.7%, CI 10.5-12.8). By contrast, the prevalence of NIDDM was similar in men (12.1%, CI 10.9-13.4) and women (11.7%, CI 10.5-12.8) for all ethnic groups combined. The sex difference in IGT prevalence was seen in all ethnic groups, but for NIDDM, the sex difference was not consistent across ethnic groups. However, age- and sex-standardized prevalence of IGT and NIDDM was remarkably similar across ethnic groups (16.2 and 12.4% in Hindu Indians, 15.3 and 13.3% in Muslim Indians, 17.5 and 10.4% in Creoles, and 16.6 and 11.9% in Chinese, respectively). Three new cases of diabetes were diagnosed for every two known cases. The high prevalence of abnormal glucose tolerance in Indian subjects is consistent with studies of other migrant Indian communities, but the findings in Creole and, in particular, Chinese subjects are unexpected. Potent environmental factors shared between ethnic groups in Mauritius may be responsible for the epidemic of glucose intolerance. PMID- 2307297 TI - The effect of tinnitus on ABR latencies. AB - Comparisons were made of the ABR latencies of tinnitus (T) and nontinnitus (NT) patient groups balanced for age and gender and matched for acoustic reflex threshold (ART)s, 1000 to 4000 Hz and 4000 Hz auditory thresholds, and normal hearing. In the ART match, prolongations of wave I [t(94) = 4.42, p less than 0.001], wave III [t(94) = 2.72, p less than 0.01], and wave V [t(94) = 3.32, p less than 0.01] and the III-V interval [t(94) = 2.48, p less than 0.02) were seen in T subjects. Wave I in 1 to 4 kHz matched [t(62) = 3.13, p less than 0.005] and normal-hearing subjects [t(30) = 2.58, p less than 0.01] was prolonged in T females. The utility of using wave I as a diagnostic indicator for tinnitus in females is discussed. PMID- 2307298 TI - Dichotic listening in a child with a cerebral lesion: the "paradoxical" ipsilateral ear deficit. PMID- 2307299 TI - Transient elevation of threshold of the neonatal auditory brain stem response. AB - Auditory brain stem responses (ABRs) of 33 high risk, full term or near term newborns with transient elevation of ABR threshold (transient group) were compared with those of normal infants (normal group) and high-risk infants with known conductive (conductive group) and known sensorineural hearing loss (sensorineural group). ABRs of infants in the transient group initially were not significantly different from those of the conductive group in terms of wave I latency, wave V latency, and the slope of the latency-intensity (L-l) function of wave V. In infants with transient unilateral threshold elevation, significantly shorter interpeak latencies were recorded in the affected ear than in the ear that passed. This finding has been previously described in infants with conductive disorders. On follow-up, ABRs in the transient group closely resembled those of the normal group with respect to the same measures. Otologic histories in the transient group were unremarkable in the majority of cases. Increased slope of the L-l function in infants with confirmed conductive disorders was an unexpected finding. Previous studies of patients with conductive loss had not revealed a significant deviation from normal for this measure. An age interaction for the effect might explain the discrepancy between this and previous studies. PMID- 2307300 TI - Directionality in the interpretation of clinical auditory brain stem response measures. AB - Clinical auditory brain stem response latency measures are conventionally evaluated for abnormality by reference to normative laboratory values in standard deviation units. This note suggests that the directionality of the test hypothesis should be considered when the clinical ABR is evaluated for abnormality at a predetermined level of confidence. PMID- 2307301 TI - Evaluation of an in-situ output probe-microphone method for hearing aid fitting verification. AB - Several hearing aid prescription procedures specify frequency gain functions in terms of the desired levels of amplified speech. The most direct method for verifying hearing aid fittings based on these procedures requires a measurement of amplified speech in the ear canal. This paper describes the evaluation of a probe microphone measurement procedure designed to measure amplified speech to verify hearing aid fittings using the MSUv3 prescription procedure. With minor modifications, the same protocol could be used with other prescriptive procedures. Hearing aids were fitted to a group of subjects with sensorineural hearing impairment. Data derived from the fittings were analyzed to assess several issues relating to the procedure itself and to prescriptive fittings in general. The main results were: (1) with over the ear hearing aids, most prescriptions can be matched with an RMS error of 5 dB or less through the frequency range from 500 to 2500 Hz; (2) even though actual fittings usually do not perfectly correspond with their prescriptions, differences among frequency gain prescriptions are preserved in hearing aid fittings if the RMS error of the fitting is 5 dB or less; (3) if sound field stimuli presented to the hearing aid are precisely controlled, an in situ output verification method produces valid results; (4) when hearing aids are fitted with gain similar to that prescribed by the MSUv3 procedure, the maximum comfortable speech input level is typically about 72 dB; (5) the SSPL90 prescription generated by the MSUv3 procedure overestimates desired SSPL90 by 7 dB on average. PMID- 2307302 TI - Hearing aid gain and frequency response requirements for the severely/profoundly hearing impaired. AB - The optimal frequency response slope, from the low frequencies (250 or 500 Hz) to 2000 Hz, was estimated for each of 46 severely or profoundly hearing-impaired adults. The estimates were derived from paired comparison judgments of speech filtered to simulate different frequency response conditions, from home trials and ratings of different tone settings of high-powered, behind-the-ear hearing aids, and for 28 subjects, from speech recognition testing. The estimated optimal response, expressed as the slope from 250 to 2000 Hz and as the slope from 500 to 2000 Hz, was compared with the response prescribed by the National Acoustic Laboratories (NAL) procedure and its relationship to audiometric variables was analyzed. Insertion gain was measured for the preferred volume setting with the best frequency response. Preferred gain was typically about 10 dB higher than the NAL prescribed gain. Considering these results in relation to other data, it appears that the "half-gain" rule ceases to apply when HTL exceeds about 70 dB. The estimated optimal frequency response agreed with the NAL response for some subjects but relatively more low frequencies were required for between a third and half of the subjects, depending upon how frequency response is expressed. Generally, more low frequencies were required if HTL at 2000 Hz exceeded 95 dB, whereas the NAL response was usually appropriate for other cases. PMID- 2307303 TI - Electrically evoked auditory brain stem responses (EABR) and middle latency responses (EMLR) obtained from patients with the nucleus multichannel cochlear implant. AB - Electrical auditory brain stem responses (EABR) and electrical middle latency responses (EMLR) were recorded from patients who had received the Nucleus multichannel cochlear implant system. Twenty-five sequential patients had either intraoperative or outpatient EABR testing. We also recorded EMLRs from several outpatients. EABR results were consistent among all patients tested. Wave V mean latencies were the shortest (3.82 msec) for the most apical electrode (E20) and increased slightly for the medial (E12) and basal (E5) electrodes (3.94 and 4.20 msec, respectively). Absolute latencies for all EABR component waves were observed to be 1 to 1.5 msec shorter than typical acoustic auditory brain stem response (ABR) mean latencies. We have examined the relationships between patients' EABR/EMLR and their behavioral responses to electrical stimulation. Generally, the behavioral threshold and comfort current levels were lower than the predicted values based on EABR/EMLR findings. This observation may be due in part to psychophysical loudness differences noted for pulse rates of 10 to 500 pulses per second in some of the patients that we have studied in greater detail. PMID- 2307304 TI - Perception of speech pattern contrasts using a multichannel cochlear implant. AB - The ability to perceive for suprasegmental and eight segmental speech pattern contrasts was measured on 16 adult cochlear implantees using the Nucleus multichannel prosthesis with either F0-F2 (n = 9) or F0-F1-F2 (n = 7) coding. The results of this study indicated the following: (1) The Nucleus device provided significant access to the majority of suprasegmental and segmental speech contrasts. (2) Both one- and two-format coding strategies provided good access to speech pattern contrasts. (3) Considerable intersubject differences in performance were observed, but there was no evidence to suggest that these were related to either processing scheme. (4) Although the accessibility of speech contrasts varied, the pattern of perceptual performance was interpreted in terms of an acoustic/phonetic hierarchy. (5) The Speech Pattern Contrast (SPAC) test appears to be a practical procedure for analyzing the perception of phonologically salient information about the suprasegmental and segmental components of speech. PMID- 2307305 TI - A critical reevaluation of the Quantified Denver Scale of Communication Function. AB - The Quantified Denver Scale of Communication Function (QDS) is a 25 item questionnaire developed to measure communication difficulties in adults with hearing impairment. This study reassessed the constructs, reliability, and validity of the scale, and developed a 5 item short version. The QDS was administered to 238 elderly individuals (137 with and 101 without hearing loss). Factor analysis using this sample identified only two subscale constructs as opposed to four originally proposed constructs. The validity of the new revised two-construct model was verified by four independent investigators who labeled the two constructs as measuring self isolation and communication function. The internal reliability of the revised scale was 0.97 and of both construct subscales was 0.95. Overall test-retest reliability was 0.73. Validity examined by comparing the revised scale with another well-known handicap measure, the Hearing Handicap Inventory for the Elderly, was adequate: overall scale correlations were 0.73 and subscale correlations ranged from 0.64 to 0.72. The accuracy of the revised QDS for discriminating between individuals with and without hearing loss was 73%. Stepwise discriminant analysis generated a 5 item short version scale which contained two questions from the long communication subscale and three from the long self-isolation subscale. The accuracy of the short QDS was 74%. We conclude that the revised QDS is a reliable and valid scale that can be used to assess self isolation and communication function in elderly individuals with hearing loss, and that a new 5 item short version performs as well as the original 25 item scale. PMID- 2307306 TI - Diagnostic value of vertical nystagmus recorded from ENG. AB - A patient with a cerebellar hemorrhage was evaluated using electronystagmography (ENG). Data obtained on the horizontal channel were only mildly abnormal. However, vertical nystagmus was clearly evident when the patient was tested in a darkened room with eyes open. This additional procedure may have saved the patient severe complications. With eyes open in darkness vertical nystagmus is more easily differentiated from eye blinks and clinicians are encouraged to look for this valuable central vestibular system sign. PMID- 2307307 TI - Interaural attenuation using etymotic ER-3A insert earphones in auditory brain stem response testing. AB - Click interaural attenuation (IA) was measured behaviorally and with the auditory brain stem response (ABR) in two unilaterally deaf adults with Etymotic ER-3A insert earphones, and TDH-39P and TDH-49P supraaural earphones. Stimulus crossover for each set of earphones was also determined with pure-tone audiometry. Pure-tone results agreed with previous research, showing that the ER 3A provided substantially greater IA than the supraaural earphones, particularly for low frequencies. For click stimuli, behavioral and ABR results revealed only modest, if any, improvement in IA with the ER-3A relative to the supraaural earphones. The results of this study suggest that while the ER-3A earphones provide a clear IA advantage for behavioral pure-tone audiometry, they do not eliminate the need for contralateral masking of click stimuli in ABR testing. PMID- 2307308 TI - Attenuation provided by four different audiometric earphone systems. AB - The attenuation provided by TDH earphones in MX-41/AR and P/N 51 cushions, Audiocup earphone enclosures and ER-3A insert earphones with ER3-14 foam earplugs was determined for 30 normally hearing subjects using a real-ear attenuation at threshold paradigm. The MX-41/AR and P/N 51 cushions provided about the same amount of attenuation which was less than the attenuation provided by the Audiocup enclosures. The ER-3A/ER3-14 provided the highest amount of attenuation. The MX-41/AR and ER-3A/ER3-14 attenuation values were in agreement with other studies using similar methodology. However, the attenuation provided by the Audiocup enclosures was considerably less, in the lower frequencies, than reported in two other studies. ANSI S3.1-1977 supra-aural earphone cushion attenuation values, which were determined using pure-tones presented in a free field, should be replaced by earphone cushion attenuation values determined with 1/3 octave bands of noise presented in a diffuse sound field. PMID- 2307309 TI - Subchronic toxicity evaluation of tridecyl acetate in rats. AB - Tridecyl acetate was administered to male and female Sprague-Dawley rats by oral gavage, 5 days per week for 13 weeks (90 days). Treated rats received daily doses of 0.1, 0.5, or 1.0 g/kg/day and control rats received distilled water at a dose of 1.0 g/kg/day. After 45 days an interim termination was made to evaluate potential hematologic or hepatic effects of tridecyl acetate. Blood samples were collected for routine hematology and serum chemistry determinations and liver tissue was obtained for histological examination. After 90 days all animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examination. Treatment-related effects observed in the mid and high dose groups consisted of (1) increased liver weights and/or liver/body weight ratios in both sexes at the interim and 13 week termination, (2) increased kidney weights and/or kidney/body weight ratios in both sexes at the terminal necropsy, (3) histopathologic evidence of hydrocarbon nephropathy in males, and (4) a slight decrease in serum glucose levels in male rats at both the interim and terminal necropsies. The increases in liver weight are believed to be a normal physiological response to a chemical challenge. The nephropathy produced by tridecyl acetate is characteristic of that produced by a diverse group of hydrocarbons and, to date, appears to be limited to male rats. The low dose in this study was a no observed effect level. These results are indicative of an overall low degree of systemic toxicity following subchronic oral administration of tridecyl acetate at doses up to 1 g/kg body weight. PMID- 2307310 TI - The use of in vitro fertilization to detect reductions in the fertility of male rats exposed to 1,3-dinitrobenzene. AB - 1,3-Dinitrobenzene (DNB) is an intermediate chemical in the manufacture of dyes and explosives and its toxic effects include specific damage to the Sertoli cells of the testis. This investigation determined the effect a toxic insult to Sertoli cells had on the functional capacity of developing germ cells as assessed by in vitro fertilization. Male rats were given a single, oral dose of 5, 15, or 25 mg DNB/kg. At selected times after treatment, spermatozoa recovered from the cauda epididymidis were tested for fertilizing capacity using in vitro fertilization techniques and the testicular response to DNB was determined by histological examination. Treatment with 15 and 25 mg DNB/kg resulted in substantial exfoliation of germ cells between 0.5 and 3.5 weeks after exposure and again after 4.5 weeks; seminiferous tubules which were not depleted showed signs of disrupted spermatogenesis. Reduced sperm fertilizing capacity in vitro was observed from 1.5 to 5 weeks and between 7.5 and 8.5 weeks after treatment with 15 and 25 mg DNB/kg. There were slight, but significant, reductions in fertility at 3, 5.5, 7.5, and 8.5 weeks after dosing with 5 mg DNB/kg. These data suggested that DNB did not affect all Sertoli cells equally, but acted in a stage-specific manner. Stages III, IV, XII, and XIV were most vulnerable to the toxicant. Germ cells associated with an affected Sertoli cell were usually sloughed off, resulting in lowered fertility at the time when these cells should have reached maturity in the epididymis. The extent of the testicular lesions and the loss of fertility were dose dependent. This investigation confirmed the use of in vitro fertilization to detect the effects of testicular toxicants. PMID- 2307311 TI - Effects of chronic treatment with the leukotriene D4 antagonist compound LY171883 on Fischer 344 rats and rhesus monkeys. AB - One-year toxicity studies were done to evaluate potential toxic effects associated with chronic exposure of rats and monkeys to the leukotriene antagonist LY171883. Rats were fed dietary doses of 0.0, 0.01, 0.03, or 0.1%, equivalent to approximately 0, 5, 15, or 50 mg/kg of body weight/day. Monkeys were given daily nasogastric gavage doses of 0, 30, 75, or 175 mg/kg of body weight. No treatment-related effects occurred in physical, behavioral, ocular, food consumption, or urinalysis parameters in either species. Mild dose-related hepatotoxicity occurred in rats given approximately 15 or 50 mg/kg of LY171883. The hepatotoxicity was characterized by liver enlargement associated with induction of hepatic peroxisomal beta-oxidation and microsomal drug metabolism. Male rats also had hepatocellular fatty change, centrilobular hypertrophy of hepatocytes, and increased levels of serum alanine transaminase and total bilirubin. Other effects in rats included minimal decreases in hematocrit values, decreases in serum triglycerides and cholesterol, and increased kidney weight. The monkeys tolerated daily oral doses of LY171883 up to 175 mg/kg with only minor increases in hepatic microsomal enzyme activity and slightly increased liver and kidney weights in males. No effects occurred in monkeys given 30 mg/kg. There was no induction of hepatic peroxisomal enzymes or pathologic abnormalities in monkeys treated with LY171883. The peroxisomal inductive effect was apparently a species-related effect separate from the pharmacologic activity of leukotriene antagonism. PMID- 2307312 TI - Teratological, neurochemical, and postnatal neurobehavioral assessment of METASYSTOX-R, an organophosphate pesticide in the rat. AB - The purpose of this study was to assess the embryotoxic, fetotoxic, and teratogenic potential of METASYSTOX-R (MSR) in the rat. Furthermore, the study was designed to determine if maternally toxic doses of MSR altered fetal brain acetylcholinesterase (AChE), compromised neonatal survival, growth, and development, or affected neurobehavioral development. Inseminated female rats (45/dose group) received single daily oral doses of 0, 0.5, 1.5, or 4.5 mg/kg of MSR from Days 6 to 15. Dose groups were subdivided into three termination phases: Phase I, 5 females terminated on Day 16 of gestation; Phase II, 28 females terminated on Day 20 of gestation; Phase III, 12 females terminated on Day 21 postpartum. MSR produced a dose-related reduction in maternal plasma (30-72%), red blood cell (18-56%), and brain (21-68%) cholinesterase (ChE) activity, when measured on Day 16 of gestation. The high dose of MSR significantly (p less than or equal to 0.05) reduced food consumption, suppressed body weight gain, and produced tremors in 98% of the dams. MSR administered at maternally toxic doses as high as 4.5 mg/kg was devoid of embryotoxic, fetotoxic, and teratogenic effects. Fetal brain AChE was not substantially different from control for any dose level in Day 20 fetuses. Furthermore, neonatal survival, growth, and development were unaffected and an extensive neurobehavioral testing scheme demonstrated no alteration of sensory or reflex functions, maze learning ability, or open field activity for neonates. PMID- 2307313 TI - Enhancement of pancreatic and hepatic glutathione levels in rats during cyanohydroxybutene intoxication. AB - 1-Cyano-2-hydroxy-3-butene (CHB), a cruciferous plant product, is hepatotoxic, pancreatotoxic, and elevates glutathione (GSH) in liver and pancreas. Whether GSH elevation is preceded by a depletion related to toxic insult, or whether toxicity and GSH elevation are unrelated, is not known. To evaluate the temporal relationship between toxicity and GSH levels, male Fisher 344 rats (6/group) were given CHB (200 mg/kg po) and killed up to 96 hr after dosing. At death, histological and ultrastructural evaluations and GSH/GSSG determinations were performed on liver and pancreas. In pancreas, dilatation of the cisternae of the rough endoplasmic reticulum (RER) was evident from 2 hr, becoming progressively more severe 4 and 6 hr after CHB. Frank apoptosis and loss of zymogen granules was evident by 6 hr, becoming widespread by 12 hr. Recovery had commenced by 72 hr, and 50% of treated rats had normal pancreata by 96 hr. No hepatic lesions were observed at this dose. Pancreatic GSH was depressed below 20% at 2 and 4 hr, rose to a maximum of 540% by 12 hr, and remained elevated in treated rats throughout the study (275% at 96 hr). Hepatic GSH only fell to 50%, rose to 150 180%, and returned to normal by 96 hr. While this pattern of depletion and rebound following exposure to hepatotoxins is common, the exaggerated and persistent elevation of pancreatic GSH is unprecedented. PMID- 2307314 TI - Pharmacological and toxicological properties of arotinoids SMR-2 and SMR-6 in mice. AB - Studies were conducted to define primary pharmacological and toxicological properties of two arotinoids, SMR-2 and SMR-6, in male B6D2F1 mice. Mice were gavaged daily for up to 22 days with retinoids in corn oil (0.1, 0.2, or 0.4 mg/kg day SMR-2 or SMR-6 or 2.5, 10, or 30 mg/kg all-trans-retinoic acid as a reference control). Toxicological and biochemical endpoints were assayed after 8, 15, and 22 days. At toxic doses, i.e., those inducing weight loss, morphological changes were observed in skin, lymph nodes, spleen, bone marrow, liver, thymus, forestomach, adrenal, bone, and testes. Biochemical alterations included elevated serum alkaline phosphatase, corticosterone, and interleukins-1, -2, and -3. Additional immune alterations included increased responsiveness of spleen cells to both thymus-dependent and thymus-independent mitogens and increases in the total number of B cells in the spleen. At doses not inducing weight loss, target organ effects included the appearance of plasma cells and infiltration of polymorphonuclear cells in lymph nodes; myeloid cell hypercellularity in bone marrow; hematopoiesis in spleen; subacute inflammation in forestomach; and periportal cytoplasmic vacuolization in liver. At the low doses, SMR-2 resulted in decreased responsiveness of spleen cells to mitogens and SMR-6 caused increased responsiveness. SMR-6 also increased interleukin-1 and-2 production at low doses. Biochemical effects included reduced activities of liver aryl hydrocarbon hydroxylase (AHH) and soluble brain protein kinase C. Overall, the results suggest that leukopoiesis and reduced liver AHH and reduced soluble protein kinase C activities are the primary and initial pharmacological and toxicological effects of retinoids. PMID- 2307315 TI - Disposition and elimination of BIOLF-143, an antiviral agent, in the rabbit. AB - BIOLF-143, (N-(dimethylamino)methylene-9- [[2-hydroxy-1 (hydroxymethyl)ethoxy]methyl]guanine), an experimental, purine-based, acyclic nucleoside was administered by iv or ip injection to adult, male and female, albino New Zealand rabbits in order to determine: (1) the pharmacokinetic disposition, (2) the route and rate of excretion, (3) the biotransformation, and (4) the acute toxicity of the agent. HPLC analysis of blood plasma concentrations of BIOLF-143 was conducted following iv injections of 50 or 100 mg/kg and ip injections of 250 mg/kg. Tissue levels of BIOLF-143 were analyzed at 60 min following an ip injection of 100 mg/kg. Metabolism/excretion studies were conducted over a 48-hr period following ip injections of BIOLF-143 (100 mg/kg). The nucleoside was rapidly distributed in the body, with the dose-dependent, estimated plasma half-life being 21-44 min. The drug molecule was not extensively bound to proteins, being quantitatively recovered from plasma (94.4 +/- 3.2%) and a variety of tissues (85-100%). The bulk of the drug (80-87%) was recovered in the urine within 48 hr of treatment, with no metabolites or unique, unidentifiable peaks being detected in HPLC chromatograms. No drug residue was found in feces. No overt toxicity or untoward signs of latent toxicity were observed in animals receiving acute doses of BIOLF-143 up to 250 mg/kg ip. A potential target organ might be the kidney since high levels of drug residue were detected 60 min post-treatment and this appeared to be the route of elimination from the body. PMID- 2307316 TI - Chronic toxicity and carcinogenicity of methylmercury chloride in B6C3F1 mice. AB - A 2-year feeding study of methylmercury chloride (MMC: 0, 0.4, 2, or 10 ppm) was conducted in B6C3F1 mice (60 mice of each sex/group) to compare chronic toxicity and carcinogenicity results with those for ICR mice from our previous study in which males of the 10-ppm group showed an increased incidence of renal tumors without any abnormal in-life parameters. In B6C3F1 mice of the 10-ppm group, neurotoxic signs characterized by posterior paralysis were observed in 33 males after 59 weeks and in 3 females after 80 weeks. In males, a marked increase in mortality and a remarkable decrease in body weight gain were observed after 60 weeks. Toxic encephalopathy consisting of neuronal necrosis of the brain and toxic peripheral sensory neuropathy were induced in both sexes in this group. Chronic nephropathy, testicular atrophy, and glandular stomach ulcer increased in incidence in the males; chronic nephropathy also increased in incidence in females. In proliferative lesions, there were significant increases in the incidence of renal adenoma and/or carcinoma (16/60) and tubular cell hyperplasia (14/60) in males of the 10-ppm group, as compared to the control group. The incidence of chronic nephropathy also increased in males of the 2-ppm group. The results of this study indicate that the susceptibility of B6C3F1 mice to renal toxicity and renal carcinogenicity is comparable to that of ICR mice, and B6C3F1 mice are more sensitive to the chronic neurotoxic effects of MMC than are ICR mice. PMID- 2307317 TI - Modulation of m-dinitrobenzene and m-nitrosonitrobenzene toxicity in rat Sertoli- germ cell cocultures. AB - Previous work has shown that m-dinitrobenzene is a testicular toxicant in rats in vivo, and in vitro produces comparable morphological changes in rat testicular Sertoli-germ cell cocultures. m-Dinitrobenzene is metabolized both in vivo and in the in vitro system to m-nitroaniline m-nitroaniline and m-nitroacetanilide. These metabolites do not provoke testicular toxicity in vivo or in vitro. We have therefore proposed a pathway for the metabolism of m-dinitrobenzene to m nitroaniline and m-nitroacetanilide, which involved the intermediate m nitrosonitrobenzene (1-nitroso-3-nitrobenzene, NNB). When tested, m nitrosonitrobenzene, at equimolar doses to m-dinitrobenzene, produced similar morphological changes in the culture system to those exhibited by m dinitrobenzene. However, m-nitrosonitrobenzene produced a greater toxicity than did m-dinitrobenzene (as measured by germ cell detachment). When the intracellular thiol levels were reduced in the cocultures pretreated with diethyl maleate, the toxicity of both m-dinitrobenzene and m-nitrosonitrobenzene was enhanced. In contrast, pretreatment of cocultures with agents known to increase cellular thiol (cysteamine) or scavenge reactive intermediates (cysteamine or ascorbate) reduced the toxicity of m-dinitrobenzene and m-nitrosonitrobenzene. We propose that m-dinitrobenzene requires metabolic activation before it can exert its toxicity to Sertoli cells, and it appears that the toxic species is m nitrosonitrobenzene or a further metabolite of m-nitrosonitrobenzene. PMID- 2307318 TI - Toxicology in the future: will the challenge be met? PMID- 2307319 TI - Paraquat pharmacokinetics using a subcutaneous toxic low dose in the rat. AB - The pharmacokinetics of paraquat were examined at a dose which produced lung disease but avoided renal damage. Following single sc injections of 14CH3 paraquat (72 mumols/kg) in male Sprague-Dawley rats, blood was sampled via indwelling jugular cannulas. Noncannulated rats were exsanguinated by cardiac puncture during a 7-day test period. Blood, liver, kidney, lung, brain, heart, spleen, gi tract, injection site, adrenals, body, urine, and feces were analyzed for total radioactivity. Histology of lung after 7 days revealed (+1) paraquat lung disease. No evidence of renal damage was observed. Paraquat was rapidly absorbed. Peak blood concentrations of 58 nmol/ml were measured at 20 min. Peak lung and kidney paraquat concentrations at 40 min were 65 and 359 nmol/g, respectively. Paraquat pharmacokinetics (NONLIN) were best described by a two compartment open model; the mean biological half-life was 40.9 hr. Eighty-five percent of the dose was eliminated in urine by 7 days. The body contained 79% of the remaining radioactivity. The residual radioactivity is associated with prolonged paraquat excretion and, perhaps, progressive lung disease. PMID- 2307320 TI - The toxicopathology of Prudhoe Bay crude oil in chicken embryos. AB - Microliter amounts of Prudhoe Bay crude oil were applied to the shell of fertile leghorn chicken eggs on Day 9 of incubation. Gross and microscopic pathological changes were examined in embryos surviving 4 days after exposure. Gross lesions seen consistently were extensive edema, superficial zones of pale hepatic tissue, distension of the heart, and enlargement of the spleen. Histologically, the pale liver tissue corresponded to areas of hepatocyte necrosis. Additional histological lesions were cellular casts and mineralization in the renal tubules, distension of the glomerular capillaries, and accumulation of hematopoietic tissue in the liver and spleen. Dose-related increases in the number of mitotic figures in hepatocytes and in weights of liver, spleen, and heart were observed. PMID- 2307321 TI - Pharmacological and toxicological evaluation of orally administered pyridostigmine in dogs. AB - Pyridostigmine bromide, a reversible cholinesterase inhibitor, was administered orally (capsule gavage) to beagle dogs (10-15 months of age) of both sexes once daily at 5, 10, or 20 mg/kg for 14 days; every 8 hr at 2 or 5 mg/kg for 28 days; or every 8 hr at 0.05, 0.5, or 2 mg/kg for 3 months as part of its preclinical safety assessment. A small portion of the dogs receiving pyridostigmine for 3 months were allowed an untreated recovery period of an additional 3 months. Daily doses of 10 or 20 mg/kg were lethal to some of the dogs when given for up to 14 days and caused severe intestinal distress, including diarrhea, emesis, and reddened feces in all animals. The cause of death was intestinal intussusception. Signs of systemic toxicity apparent at these doses included hypersalivation and tremors. Similar but less severe effects were produced by 5 mg/kg per day; plasma cholinesterase activities were inhibited by all three doses in a dose-related manner. Signs of toxicity in the 28-day and 3-month studies were generally limited to the gastrointestinal tract and included diarrhea or soft stools and reddened or mucoid-containing stools; these signs appeared to reverse upon discontinuation of the drug. A single dog at 2 mg/kg every 8 hr developed an apparent intussusception. There were no pathological changes in clinical chemistry, hematology, or urinalysis parameters associated with doses of 0.05, 0.5, or 2 mg/kg every 8 hr for up to 3 months, nor were any drug-related lesions observed upon gross necropsy and microscopic evaluation of the major tissues and organs. Red blood cell (RBC) acetylcholinesterase (AChE) activities in the 3 month study were inhibited by approximately 10, 50, and 70% in the 0.05, 0.5, and 2 mg/kg every 8-hr dose groups, respectively, and these degrees of inhibition were maintained throughout the period of treatment. These data suggest that prolonged oral administration of pyridostigmine at doses sufficient to cause profound and sustained inhibition of RBC AChE activity (i.e., as high as 70%) cause mainly local, gastrointestinal distress related to altered intestinal motility. At the extreme, this can be manifested as a life-threatening intestinal intussusception. Systemic anticholinesterase effects (other than enzyme inhibition) were observed only at doses of 2 mg/kg and greater, while local (gastrointestinal) effects and inhibition of RBC AChE were observed at doses as low as 0.05 mg/kg. PMID- 2307322 TI - Acute inhalation toxicity of T-2 mycotoxin in the rat and guinea pig. AB - In this study, concentration-response parameters were determined for rats and guinea pigs systematically exposed to an aerosol of T-2 toxin. The LC50 for a 10 min exposure to T-2 toxin aerosol was 0.02 mg T-2/liter air for rats and 0.21 mg T-2/liter air for guinea pigs. Data from total T-2 deposition in rats and guinea pigs exposed to their respective LC50 aerosol concentration gave an LD50 of 0.05 mg T-2/kg body weight for the rat and 0.4 mg T-2/kg body weight for the guinea pig. These data show that inhaled T-2 toxin is approximately 20 times more toxic to the rat (0.05 mg T-2/kg body wt inhaled vs 1.0 mg T-2/kg body wt ip) and at least twice as toxic to the guinea pig (0.4 mg T-2/kg body wt inhaled vs 1-2 mg T 2/kg body wt ip) than ip administered T-2 toxin. Histopathologic examination of major organs in both the rat and guinea pig after respiratory exposure to T-2 toxin indicated that lesions were similar to those described after systemic administration of the toxin. Gross and microscopic alterations of respiratory tract tissue after T-2 aerosol exposure were minimal and could not account for the increase in toxicity. PMID- 2307323 TI - Biphasic changes in mouse motor activity during exposure to toluene. AB - There are few careful studies of the effects of solvents on unlearned animal behavior during acute exposure, despite the importance of the prevention of acute behavioral or neurological effects in the workplace. To examine the effects of toluene on the locomotor activity of mice, we divided a plastic vacuum desiccator into six wedge-shaped compartments with diffusing plena above and below. A phototransistor in each wedge measured the movement of individual mice, thus each mouse could serve as its own control. Six groups of six mice were exposed to each of five concentrations of toluene (300-3000 ppm) or air in a Latin-square design for 1 hr on Tuesdays and Fridays. Individual animals differed in their sensitivity to toluene, and the use of each subject as its own control permitted the detection of effects at lower concentrations. The magnitude of the effect was related to concentration, the duration of exposure, and the control rate of activity. Activity increases were obvious at 560 ppm, and decreases at 3000 ppm. The concentrations at which these reversible activity increases occurred are the lowest reported to date and are only slightly greater than those that have been reported to alter human reaction time. This preparation displays sensitivity comparable to that observed in published studies of the effects of toluene on learned behavior in the rat. PMID- 2307324 TI - The distribution of [14C]acrylamide in rainbow trout studied by whole-body autoradiography. AB - The distribution of [2,3-14C]acrylamide was studied in fingerling rainbow trout by whole-body autoradiography. Fish weighing approximately 7 g were injected ip with 3.2 mg/kg [14C]acrylamide (0.1 microCi/g). One group of fish was kept in a fresh flowing water tank and frozen in dry ice/hexane 22 hr after injection; another group was placed in a separate tank of fresh flowing water and frozen 120 hr after treatment. A third group of fish served as nontreated controls. The autoradiographs of the fish at 22 hr show the highest concentration of radioactivity in the kidney, urinary bladder, blood, gallbladder, intestinal contents, and lens of eye. Lesser amounts of radioactivity are seen in the CNS, liver, and gills. Very low concentrations are seen in muscle. By 120 hr the only high concentrations are seen in gallbladder and lens of the eye. Lesser amounts are seen in the sclera, vertebrae, CNS, kidney, wall of intestine, and discrete spots in subcutaneous tissue presumed to be chromatophores. Low amounts are seen in muscle, the tissue usually consumed by man. PMID- 2307325 TI - Effectiveness of chelation therapy with time after acute uranium intoxication. AB - The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5 aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy. PMID- 2307327 TI - The Human Genome Initiative: a different type of research. PMID- 2307326 TI - Effects of physostigmine on the cardiopulmonary system of conscious pigs. AB - Physostigmine, as a pretreatment candidate for nerve agent poisoning, was examined for cardiopulmonary side effects. Cardiovascular and pulmonary parameters were monitored in unanesthetized domestic pigs which received pulmonary arterial infusion of 5 micrograms/kg/min physostigmine salicylate for 2 hr. A level of 74% inhibition of red blood cell (RBC) acetylcholinesterase (AChE) activity was attained in 45 min, and this level of carbamylation increased only slightly during the remaining infusion period. In addition to this large change in AChE activity, minor changes were observed in hematocrit, heart rate, body temperature, mean aortic pressure, pulmonary arterial wedge pressure, and pulmonary artery pressure. Typically, these parameters showed a trend toward elevated levels. Blood gases, pH, respiratory rate, tidal and minute volume, cardiac output, nonelastic resistance, and dynamic compliance were not significantly different from baseline values. The unanesthetized pig responds to physostigmine in a manner similar to that reported for other species and appears to be a suitable model for evaluating cardiopulmonary effects of cholinesterase inhibitors. PMID- 2307328 TI - Fractal geometry in mosaic organs: a new interpretation of mosaic pattern. AB - Fractal geometries have been widely observed in nature. The formulation of mathematical treatments of non-Euclidean geometry has generated models of highly complex natural phenomena. In the field of developmental biology, branching morphogenesis has been explained in terms of self-similar iterating branching rules that have done much toward explaining branch patterns observed in a range of real tissue. In solid viscera the problem is more complicated because there is no readily available marker of geometry in parenchymal tissue. Mosaic pattern provides such a marker. The patches observed in mosaic liver are shown to be fractal, indicating that the pattern may have arisen from a self-similar process (i.e., a process that creates an object in which small areas are representative of, although not necessarily identical to, the whole object). This observation offers a new analytical approach to the study of biologic structure in organogenesis. PMID- 2307329 TI - Glutathione correlates with lipid peroxidation in liver mitochondria of triiodothyronine-injected hypophysectomized rats. AB - The temporal relationship of changes in state 3 respiration, lipid peroxidation, and glutathione (GSH) content was investigated in liver mitochondria of hypophysectomized rats after an injection of 3,3',5-triiodo-L-thyronine (T3). Lipid peroxidation induced by ADP/Fe3+/NADPH was determined by the amount of malondialdehyde formed. Hypophysectomy decreased respiration and lipid peroxidation (from 19.88 +/- 3.04 to 14.19 +/- 1.14 nmol malondialdehyde.mg protein-1.10 min-1) but increased GSH content (from 7.06 +/- 2.08 to 12.46 +/- 3.58 nmol/mg protein). Daily injections of a low dose (5 micrograms/100 g) of T3 for 7 days restored the parameters. Time course (up to 96 h) of these changes was followed after one injection of a moderate (100 micrograms/100 g) and high (1000 micrograms/100 g) dose of the hormone. Respiration showed a significant increase at 24 h and declined slightly at 96 h. There was a slow loss of respiratory control ratio after 24 h. Lipid peroxidation remained unchanged at 24 h and showed a gradual increase, becoming significantly higher at 72-96 h depending on the hormone dosage. Changes in GSH content followed a time course similar to that of lipid peroxidation except that it showed a decrease instead of an increase. There was a high degree of inverse linear correlation between lipid peroxidation and GSH (correlation coefficient = 0.95). Because GSH is required for detoxification of hydroperoxides generated by the respiratory chain, it is suggested that lipid peroxidation may play a major role in the modulation of intramitochondrial GSH. PMID- 2307330 TI - Calcium waves in mammalian heart: quantification of origin, magnitude, waveform, and velocity. AB - A dual, digital, indo-1 fluorescence imaging system was used to obtain high-speed ratiometric images of [Ca2+]i waves in single voltage-clamped mammalian cardiac cells. The spatiotemporal origin of [Ca2+]i waves in depolarized cells was detected as the spontaneous appearance, over 100-300 ms, of domelike regions of elevated [Ca2+]i, approximately 20 microns in diameter and 300 nM at the center. Images of [Ca2+]i taken at 67-ms intervals during propagation of [Ca2+]i waves revealed that the [Ca2+]i wave front was 1) constant in shape, 2) spatially steep, typically rising from 500 to 1200 nM in about 10 microns, and 3) propagating at constant velocity, typically 100 microns/s at 22 degrees C. The observed spatial and temporal patterns of origin and propagation of [Ca2+]i waves are consistent with the hypothesis that [Ca2+]i waves arise from propagating Ca2(+)-induced release of Ca2+ mediated by diffusion of cytosolic Ca2+. The [Ca2+]i waves are smaller in peak magnitude and can occupy a larger fraction of the cell than thought previously on the basis of indirect observations. PMID- 2307331 TI - COBIOTECH's role in biotechnology worldwide. PMID- 2307332 TI - Animal rights. PMID- 2307333 TI - Dental silver tooth fillings. PMID- 2307334 TI - Distribution of microfold cells (M cells) in human follicle-associated epithelium. PMID- 2307335 TI - Vitamin K protects cultured rat hepatocytes against carbon tetrachloride-induced damage. PMID- 2307336 TI - Simultaneous production of hepatic lesions and circulating antimitochondrial antibody in an experimental animal model of primary biliary cirrhosis. PMID- 2307337 TI - Prevalence of IgM anti-HBc among HBsAg carriers in Okinawa, Japan. AB - To evaluate the presence of IgM antibody to hepatitis B core antigen (IgM anti HBc) in hepatitis B surface antigen (HBsAg) carriers, serial serum specimens of 698 carriers in Okinawa, Japan, from infants to adults, were studied by radioimmunoassay. IgM anti-HBc was detected in 7.6% of these carriers, with no difference between the sexes. The prevalence of IgM anti-HBc was higher in the age groups 0-9, 50-59 and over 60 than in the age group 20-29 and 30-39 years. In hepatitis B e antigen (HBeAg) positive carriers, the prevalence of IgM anti-HBc was 15.4%, a value significantly higher than in the HBeAg-negative carriers at 6.6%. In carriers with liver damage, the prevalence of IgM anti-HBc was 33.3%, a level significantly higher than the 6.3% in carriers without liver damage. However, IgM anti-HBc was detected in 34 carriers with neither HBeAg nor liver damage. These carriers are being closely followed. We discussed the presence of IgM anti-HBc in association with HBeAg or liver damage. The presence of IgM anti HBc among HBsAg carriers was closely associated with liver damage. PMID- 2307338 TI - Effects of a concanavalin A-binding biliary glycoprotein on nucleation time of gallbladder bile. AB - A study was performed to determine quantitative differences in the total protein concentration of gallbladder bile from gallstone patients and to isolate nucleation-promoting factors from the bile. Total protein concentrations in cholesterol gallstone bile (3.6 +/- 0.6 mg/ml, mean +/- SD, n = 10), calcium bilirubinate gallstone bile (4.2 +/- 1.1 mg/ml, n = 10), black pigment gallstone bile (1.9 +/- 0.6 mg/ml, n = 4) and control gallbladder bile (2.3 +/- 0.5 mg/ml, n = 9) were not significantly different. Also no statistically significant differences in cholesterol saturation index were found among these groups. Gallbladder bile from cholesterol gallstone patients showed significantly faster nucleation than that of controls, calcium bilirubinate gallstone, or black pigment gallstone patients. We partially purified biliary glycoproteins proteins from cholesterol gallstone bile or calcium bilirubinate gallstone bile by chromatography on concanavalin A Sepharose. Nucleation time was measured following the addition of these proteins to control bile in vitro. The glycoproteins obtained from cholesterol gallstone bile had significant nucleation promoting activity, but nucleation time was not changed following the addition of biliary glycoproteins from calcium bilirubinate gallstone patients. These results suggest that qualitative differences in individual proteins of gallbladder bile are responsible for nucleation-promoting activity in vitro. PMID- 2307339 TI - Gallbladder contractility and gallstone formation in the Richardson Ground Squirrel. AB - The pathogenesis of cholesterol cholelithiasis in man is probably multifactorial and the mechanism by which gallbladder stasis occurs in gallstone patients has not been studied in detail. In the present study, time-dependent changes in gallbladder motility of the Richardson Ground Squirrels were investigated. 100 of animals were examined for their contractile responses of gallbladders to CCK-OP and Ach in vitro. Also, biochemical changes of serum and bile were investigated. There were no significant differences in motility of gallbladders to CCK-OP or Ach between control and cholesterol-fed animals. The results of this study indicate that gallbladder muscle contractility remains unchanged during the dietary induction of cholesterol gallstones in the Richardson Ground Squirrel. PMID- 2307340 TI - Effects of steroids and human chorionic gonadotrophin on in vitro oocyte final maturation in two marine flatfish: the dab, Limanda limanda, and the plaice, Pleuronectes platessa. AB - This study investigated the role of gonadotrophin and steroids in the induction of in vitro oocyte maturation in dab (Limanda limanda) and plaice (Pleuronectes platessa), two marine flatfish (Pleuronectiformes) in which the oocytes mature and ovulate in groups (or batches). Clusters of folliculated oocytes were incubated for 3 days with a range of doses of either human chorionic gonadotrophin (HCG) or synthetic steroids with a wide range of structures. They were also incubated with extracts from cultures of HCG-stimulated ovaries. Oocytes were always more responsive to HCG than to steroids, and the median efficient doses obtained with HCG were negatively correlated with oocyte diameters. Bioassay sensitivity to steroids was low when compared with other teleosts, and intraassay variability was high, particularly in plaice. Despite the high variability, a common pattern in specificities to steroids was obtained for the two species, which was also similar to other teleost species. Among the most effective steroids found were 17 alpha,20 beta-dihydroxy-4-pregnen-3-one and 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one. Extracts from incubates were ineffective. The significance of these findings and possible ways to reduce assay variability and improve sensitivity are discussed. PMID- 2307341 TI - Plasma levels of ovarian steroids, including 17 alpha-20 alpha-dihydroxy-4 pregnen-3-one and 3 beta,17 alpha,20 alpha-trihydroxy-5 beta-pregnane, in female dabs (Limanda limanda)--marine flatfish--induced to mature and ovulate with human chorionic gonadotrophin. AB - Human chorionic gonadotrophin (HCG) effectively stimulated oocyte final maturation and ovulation in female dabs (Limanda limanda) within 5 days of injection, and this was accompanied by significant changes in blood plasma steroid levels. The steroids which showed the greatest responses to the HCG injections were the ones previously found to be the major products of the ovaries in vitro: 17 alpha-20 alpha-dihydroxy-4-pregnen-3-one (17,20 alpha-P) and 3 beta,17 alpha,20 alpha-trihydroxy-5 beta-pregnane (3 beta,17,20 alpha-P-5 beta). 17,20 alpha-P responded more rapidly with peak levels after 32 hr of injection (115 ng ml-1), but 3 beta,17,20 alpha-P-5 beta reached higher levels ca. 12 hr later (320 ng ml-1). Levels of both steroids were not significantly different from initial values by the time of ovulation. 17 alpha,20 beta-Dihydroxy-4 pregnen-3-one, which is likely to be the oocyte maturation-inducing steroid (MIS) in the dab, showed a significant but very variable rise in levels (between 1 and 10 ng ml-1 in individual fish). 17 alpha-Hydroxy-4-pregnene-3,20-dione levels peaked at 6 ng ml-1 between 30 and 36 hr after HCG injection. Of the other C21 steroids identified in the ovaries of teleosts, 17 alpha,20 beta-21-trihydroxy-4 pregnen-3-one could not be detected, and 17 alpha,21-dihydroxy-4-pregnene-3,20 dione (11-deoxycortisol) showed nonsignificant changes compared to the saline injected controls. HCG caused a decrease in estradiol-17 beta levels within 24 hr, but levels then rose again to a maximum of 8.2 ng ml-1 at ovulation time, possibly caused by the presence of vitellogenic oocytes in the ovaries. Changes in testosterone levels, however, were not significantly different between HCG- and saline-injected females. The role of HCG-responsive C21 steroids in the dab is discussed. PMID- 2307342 TI - Seasonal changes in serum gonadotropin, testosterone, 11-ketotestosterone, and estradiol-17 beta levels and their relation to tumor burden in gonadal tumor bearing carp x goldfish hybrids in the Great Lakes. AB - The hybrids of carp (Cyprinus carpio) and goldfish (Carassius auratus) collected from the lower Great Lakes between 1978 and 1981 exhibited a high frequency of gonadal neoplasms and apparent sterility, conditions which were rare in the parental species. A pronounced hyperplasia of gonadotropic cells in hybrids resulted in the accumulation of large stores of biologically active gonadotropin (GtH) in the pituitary gland. Serum GtH levels were generally higher in hybrids than in carp collected from the same areas, but seasonal trends were similar for both species. Among hybrids, tumored individuals had higher serum GtH levels than nontumored individuals. Serum levels and seasonal trends for testosterone (T), 11 and ketotestosterone (11-KT), and estradiol-17 beta (E2) were, for the most part, similar when carp and nontumored hybrids of the same gender were compared. Serum levels of T and 11-KT (but not E2) were generally higher in tumored hybrids when compared to nontumored individuals. High serum steroid levels were related to a specific tumor type, possibly of Sertoli cell origin. Although the etiology of the gonadal tumors is not yet known, the serum levels of gonadal steroids in hybrids make it unlikely that a lack of steroidal feedback is responsible for the gonadotrop hyperplasia. PMID- 2307343 TI - Gonadal hormones inhibit the induction of metamorphosis by thyroid hormones in Xenopus laevis tadpoles in vivo, but not in vitro. AB - Although the major hormones controlling amphibian metamorphosis are those of the thyroid, other hormones, notably prolactin and the adrenal steroids, modulate the effects of thyroid hormones (TH). Some authors report that the gonadal steroids stimulate the metamorphic actions of TH whereas others report inhibition. The aims of the present study were to determine the effects of gonadal steroids on TH induced metamorphosis in Xenopus laevis and to determine the site of action of these steroids. In all cases, hormones were added to the water in which the tadpoles were swimming. The gonadal steroids, testosterone and 17 beta-estradiol, inhibited triiodothyronine (T3)-induced metamorphosis in living, premetamorphic tadpoles of X. laevis. Both steroids, at 3.4 microM, prevented the reduction in body weight and the shrinkage of head and alimentary canal brought about by 1 nM T3. In contrast, 3.4 microM corticosterone stimulated T3-induced metamorphosis. Addition of 100 nM T3 to the medium induced a large reduction in size of X. laevis tails cultured in vitro. The antagonistic effects of testosterone were not reproduced in such cultures, whereas the synergistic action of corticosterone was maintained. Testosterone had no effect upon the specific binding of T3 to X. laevis tail tissue, whereas corticosterone increased such binding. These findings indicate that, while corticosterone stimulates the metamorphic actions of T3 by acting directly in the peripheral tissues, the gonadal steroids, particularly testosterone, inhibit T3 by acting at a more central site. Prolactin is known to antagonize the metamorphic actions of T3 and one such central action could be the stimulation of prolactin synthesis. However, testosterone inhibited the prometamorphic actions of bromocriptine, which stimulates metamorphosis by inhibiting production of prolactin. Thus the central action of testosterone is unlikely to be a stimulation of prolactin production. PMID- 2307344 TI - Ontogeny of the effect of purified chicken growth hormone on the liver 5' monodeiodination activity in the chicken: reversal of the activity after hatching. AB - The ontogeny of the effect of chicken growth hormone (c-GH) on the liver 5' monodeiodination (5'-D) activity was studied in chickens starting from 14-day-old embryos until 5-week-old chickens. Ten micrograms of the purified hormone was injected intravenously and after 2 hr, blood and liver samples were taken. In all embryonic stages tested, c-GH stimulated the peripheral thyroxine (T4) to triiodothyronine (T3) conversion as demonstrated by the increased plasma T3 level and liver 5'-D activity while the plasma reverse T3 (rT3) level was decreased. In chicks 1 day after hatching, GH was still able to increase the plasma T3 level and the liver 5'-D activity. However, in 2-day-old chicks, this stimulation had completely disappeared, while the control value of the plasma T3/T4 ratio was considerably higher than the day before. The effect of c-GH injection gradually turned into a decrease of 5'-D activity and plasma T3 in 5- and 7-day-old chicks. Further on, no effect of c-GH could be found in 2- to 4-week-old growing chickens, but in 5-week-old GH-injected animals the plasma T4 and rT3 level decreased again, although no significant effect on T3 or liver 5'-D activity could be demonstrated. PMID- 2307345 TI - Circulating estradiol and the activation of male and female copulatory behavior in Japanese quail (Coturnix japonica). AB - Previous experiments using systemic and preoptic area (POA) hormone treatments have shown that aromatization of testosterone (T) to estrogen (E) is essential for activation of male-typical copulatory behavior in castrated male Japanese quail (Coturnix japonica). Two experiments were conducted to determine whether circulating estrogen levels characteristic of normal intact males are high enough to activate male-typical or female-typical copulatory behavior. In Experiment 1, blood samples were drawn every 4 hr from groups of sexually active male quail housed under a 16L:8D light-dark cycle, and assayed for estradiol (E2) concentration. The mean +/- SEM serum E2 was 54.2 +/- 3.6 pg/ml, and no daily cycle in serum E2 was seen. The males were then tested for sexual behavior; 88% mounted females, and 23% crouched when mounted by males. In Experiment 2, 51 males were castrated and implanted with Silastic tubes containing estradiol benzoate (EB) and/or cholesterol designed to produce five different levels of serum E2, then tested for male- and female-typical copulatory behavior and bled. The serum E2 in EB-implanted quail which mounted (253 +/- 30 pg/ml) was significantly higher than that of intact quail in Experiment 1, and only 10.2% of intact males had serum E2 as high as the minimum associated with mounting in EB implanted males. These results show that serum E2 levels in intact males are not high enough to support male-typical copulation, and that aromatization in the POA to produce locally high E2 levels may be required. In addition, it was found that the threshold serum E2 to elevate receptivity significantly was 3.6 times the intact male level, and only slightly higher than serum E2 reported for intact females. Thus the lack of receptivity in intact males is probably due to insufficient circulating E2, and the male is not defeminized with respect to sensitivity to E2 for activation of receptivity. PMID- 2307346 TI - Endocrine and behavioral responses to aggression and social dominance in the green anole lizard, Anolis carolinensis. AB - Adult males of the small arboreal iguanid lizard, Anolis carolinensis, will fight and form social dominance hierarchies when placed in habitats with limited resources. The relationships between time since initial aggressive interaction, relative social dominance, reproductive activity, and corticosterone and androgen levels were determined for 34 pairs of lizards. A discriminant analysis established a "dominance index" which indicated that over 90% of the difference between individuals who had won or lost aggressive interactions (putative social dominants and subordinates) was attributable to a single discriminant function reflecting altered body color, perch site selection, and circulating androgen. Animals that had darker body color also selected lower perch sites and had depressed rates of courtship relative to winners of fights and were thus designated as social subordinates. These animals also had levels of circulating androgen significantly lower than that of dominants, but circulating corticosterone was not significantly affected. Winners of fights showed a dramatic surge in circulating androgen at 1 hr but returned to near control values by 1 week; losers, however, showed depressed circulating androgen levels at 1 week. PMID- 2307347 TI - Vitellogenin synthesis in andrectomized males of the terrestrial isopod, Armadillidium vulgare (malacostracan Crustacea). AB - When adult females of Armadillidium vulgare were ovariectomized, the fat body continued to synthesize vitellogenin. On the other hand, females transplanted with androgenic glands decreased the synthetic activity for vitellogenin in their fat body. In order to elucidate effect of the androgenic hormone for vitellogenin synthesis, the occurrence of vitellogenin was studied with andrectomized males. Vitellogenin was estimated, using rocket immunoelectrophoresis. Vitellogenin synthesis in the fat body was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography. After andrectomy, males ceased elongation of the endopods (copulatory organs) and then vitellogenin was present in their hemolymph. Their vitellogenin titer continued to rise until it reached approximately three times higher than that of normal females. The accumulation level of vitellogenin was comparable with that of ovariectomized females. However, the activity of vitellogenin synthesis was at a low level in the fat body culture of andrectomized males, similar to ovariectomized females. These results indicate that andrectomized males are capable of vitellogenin synthesis, so one of the effects of the androgenic hormone is to inhibit vitellogenin synthesis. In A. vulgare, ovarian factors may not be involved in the induction of vitellogenin synthesis. PMID- 2307348 TI - Effects of depolarizing concentrations of K+ and reduced osmotic pressure on 45Ca2+ accumulation by the rostral pars distalis of the tilapia (Oreochromis mossambicus). AB - The accumulation of 45Ca2+ into tilapia prolactin (PRL) tissue was examined under conditions which alter prolactin release. In initial experiments, PRL tissue was incubated in medium containing 12 microCi/ml 45Ca2+ in hyperosmotic medium (355 mOsmolal). Under these conditions, 45Ca2+ accumulated steadily, reaching a plateau within 15-20 min. Subsequent exposure to La3+, which displaces Ca2+ from superficial pools in a wide variety of tissues, rapidly (within 5 min) removed nearly 70% of the 45Ca2+ associated with the tissue. Following this initial removal of 45Ca2+, the level of 45Ca2+ in the PRL tissue remained constant, and is referred to as the La3(+)-resistant pool of Ca2+. This pool of Ca2+ is thought to reflect the entry rate of Ca2+ from extracellular sources. Prolactin tissue exposed to hyposmotic medium or to depolarizing [K+], which stimulates PRL release, significantly increased 45Ca2+ accumulation in this La3(+)-resistant pool. These results indicate that reduced osmotic pressure and depolarization may alter release from tilapia PRL cells, in part, through their ability to increase the entry of extracellular Ca2+. PMID- 2307349 TI - Immunohistochemical localization of the peptide sauvagine in the skins of phyllomedusine frogs. AB - We have immunohistochemically localized immunoreactive sauvagine (ir-SV) in the skins of two species of frogs of the genus Phyllomedusa. Using rabbit antiserum against synthetic sauvagine conjugated to keyhole limpet hemocyanin, sauvagine like immunoreactivity (SVLI) was detected in the lumina of all serous glands observed and in a few mucous glands in skin sections of adult P. sauvagei and P. trinitatus. SVLI was not detected in the skin of a third species, P. azurea. In P. trinitatus tadpoles, the presence of cutaneous SVLI was first observed at the onset of metamorphosis. Larval SVLI was evident in forming serous glands, but was not seen in mucous or lipid glands. Patchy SVLI was also observed in the dermis around the chromatophores in one tadpole. Preincubation of the antiserum with synthetic SV blocked SVLI; preincubation of the antiserum with urotensin I or rat or ovine corticotropin-releasing factor reduced but did not obliterate SVLI. The presence of SV in serous and mucous glands suggests that the release and function of SV may be different for each gland type, and the presence of SVLI in some mucous glands but not others suggests that biochemically discrete populations of mucous glands exist in the frog skin. PMID- 2307350 TI - Sex differentiation in the hagfish Eptatretus stouti. AB - A detailed study was made of sex differentiation in three anteroposteriorly distributed body regions of the long gonadal fold in young Pacific hagfish (Eptatretus stouti) from 12.4 to 45 cm in length. In general, the posterior region, adjacent to the cloaca, remained undifferentiated, and only in specimens more than 28 cm long was there development of this region into a differentiated testis. On the other hand, the anterior gonadal region of all specimens under 20 cm developed continually and progressively through stages that included cystic nests of cells derived from the germinal epithelium, acquisition of follicular investments around these cells, growth of these young oocytes and break-up of their original follicular groupings, and, finally, in larger specimens, vitellogenesis. Although the earliest oocytes formed in cyst-like nests of cells, later oocytes were derived individually directly from the germinal epithelium. In larger specimens, in which testicular development occurred in the posterior part of the gonad, the anterior gonad involuted, leaving a thin structure that lacks germ cells. There were numerous exceptions to this general description of events, indicating a certain degree of lability of determination of a particular gonadal region to either male or female differentiation. Some earlier stages of female differentiation could occur in the posterior gonadal region of a few smaller animals. Some posteriorly located ovotestes (differentiated elements of both sexes) developed in a few specimens between 16 and 21 cm in length, but were not seen in larger animals. Some testicular follicles appeared in the anterior gonadal regions of three specimens between 20 and 25 cm in length, but not in specimens larger than that. Three hermaphroditic specimens between 29 and 33 cm in length were found in which there was a well-differentiated testis posteriorly and a well-differentiated ovary (vitellogenic eggs) anteriorly. Questions of hermaphroditism, lability of sex determination, and possible epigenetic influences on these phenomena are taken up in the discussion. Since this study provides the first correlation of stages of sex differentiation with animal length, it forms the basis for experimental approaches in E. stouti to analysis of mechanisms of sex determination and differentiation. PMID- 2307351 TI - Chromosome I duplications in Caenorhabditis elegans. AB - We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left half of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome. PMID- 2307352 TI - The pattern of mammalian evolution and the relative rate of molecular evolution. AB - The rates of nucleotide substitution at four genes in four orders of eutherian mammals are compared in relative rate tests using marsupial orthologs for reference. There is no evidence of systematic variation in evolutionary rate among the orders. The sequences are used to reconstruct the phylogeny of the orders using maximum likelihood, parsimony and compatibility methods. A branching order of rodent then ungulate then primate and lagomorph is overwhelmingly indicated. The nodes of the nucleotide based cladograms are widely separated in relation to the total lengths of the branches. The assumption of a star phylogeny that underlies Kimura's test for molecular evolutionary rate variation is shown to be invalid for eutherian mammals. Excess variance in nucleotide or amino acid differences between mammalian orders, above that predicted by neutral theory is explained better by variation in divergence time than by variation in evolutionary rate. PMID- 2307353 TI - Fluctuation analysis: the probability distribution of the number of mutants under different conditions. AB - In the 47 years since fluctuation analysis was introduced by Luria and Delbruck, it has been widely used to calculate mutation rates. Up to now, in spite of the importance of such calculations, the probability distribution of the number of mutants that will appear in a fluctuation experiment has been known only under the restrictive, and possibly unrealistic, assumptions: (1) that the mutation rate is exactly proportional to the growth rate and (2) that all mutants grow at a rate that is a constant multiple of the growth rate of the original cells. In this paper, we approach the distribution of the number of mutants from a new point of view that will enable researchers to calculate the distribution to be expected using assumptions that they believe to be closer to biological reality. The new idea is to classify mutations according to the number of observable mutants that derive from the mutation when the culture is selectively plated. This approach also simplifies the calculations in situations where two, or many, kinds of mutation may occur in a single culture. PMID- 2307354 TI - The evolution of latent genes in subdivided populations. AB - We define latent genes as phenotypically silent DNA sequences which may be reactivated by various genetic mechanisms. Of interest is how they and their functional counterparts can be maintained at high frequency in the face of mutation and selection pressure. We propose a two-deme, three-allele model incorporating viability selection, mutation and migration in haploid populations. It is shown that polymorphism for the three alleles can be easily maintained for a wide range of biologically meaningful parameter values. Computer simulations were employed to gain qualitative insight into the global dynamics of the system. It was found that the dynamics of the latent allele is closely correlated with that of the functional allele. In addition, bias in the migration rates can strengthen or weaken selective conditions for preservation of the functional and latent alleles. PMID- 2307355 TI - Quantitative genetics of doubled haploid populations and application to the theory of line development. AB - The line value of a genotype is defined as the expected value of all lines that can be derived from this genotype. Specific genetic effects are defined for this value: only additive and additive by additive epistatic effects are necessary. There is no dominance effect for such a value. A general expression for the covariances between related lines is given. From a design with several lines per haplodiploidized plant taken at random from a population it is possible to estimate the additive variance for line value and the variance of additive by additive epistasis for line value. Variances of higher order epistasis can be estimated with a two-factor mating design in which a cross is replaced by the population of lines that can be derived from it. With a diallel or a factorial design a direct test for the presence of homozygous by homozygous epistasis is possible. The application of the concept of line value to the theory of line development leads to simple expressions of genetic advance in one cycle of recurrent selection according to the testing system. A brief consideration of these expressions leads to the conclusion that single doubled haploid descent recurrent selection will be one of the most efficient methods for low heritabilities and with a rapid development of doubled haploid lines. PMID- 2307356 TI - The role of sdc-1 in the sex determination and dosage compensation decisions in Caenorhabditis elegans. AB - Our previous work demonstrated that mutations in the X-linked gene sdc-1 disrupt both sex determination and dosage compensation in Caenorhabditis elegans XX animals, suggesting that sdc-1 acts at a step that is shared by the sex determination and dosage compensation pathways prior to their divergence. In this report, we extend our understanding of early events in C. elegans sex determination and dosage compensation and the role played by sdc-1 in these processes. First, our analysis of 14 new sdc-1 alleles suggests that the phenotypes resulting from the lack of sdc-1 function are (1) an incompletely penetrant sexual transformation of XX animals toward the male fate, and (2) increased levels of X-linked gene transcripts in XX animals, correlated with XX specific morphological defects but not significant XX-specific lethality. Further, all alleles exhibit strong maternal rescue for all phenotypes assayed. Second, temperature-shift experiments suggest that sdc-1 acts during the first half of embryogenesis in determining somatic sexual phenotype, long before sexual differentiation actually takes place, and consistent with our previous proposal that sdc-1 acts at an early step in the regulatory hierarchy controlling the choice of sexual fate. Other temperature-shift experiments suggest that sdc-1 may be involved in establishing but not maintaining the XX mode of dosage compensation. Third, a genetic mosaic analysis of sdc-1 produced an unusual result: the genotypic mosaics failed to display the sdc-1 sexual transformation phenotypes. This result suggests several possible interpretations: (1) sdc-1 is expressed immediately, in the one- or two-celled embryo; (2) sdc-1 acts non-cell autonomously, such that expression of the gene in either the AB or P1 lineage can supply sdc-1(+) function to cells of the other lineage; (3) the X/A ratio is assessed immediately, in the one- or two-celled embryo; or (4) the X/A signal directs the choice of sexual fate in a non-cell-autonomous fashion. Finally, examination of the classes of sexual phenotypes produced in sdc-1 mutant strains suggests that different cells in the organism may not choose their sexual fates independently. PMID- 2307357 TI - Genetic evidence for two protein domains and a potential new activity in bacteriophage T4 DNA polymerase. AB - Intragenic complementation was detected within the bacteriophage T4 DNA polymerase gene. Complementation was observed between specific amino (N) terminal, temperature-sensitive (ts) mutator mutants and more carboxy (C) terminal mutants lacking DNA polymerase polymerizing functions. Protein sequences surrounding N-terminal mutation sites are similar to sequences found in Escherichia coli ribonuclease H (RNase H) and in the 5'----3' exonuclease domain of E. coli DNA polymerase I. These observations suggest that T4 DNA polymerase, like E. coli DNA polymerase I, contains a discrete N-terminal domain. PMID- 2307358 TI - Cytoplasmically inherited reproductive incompatibility in Tribolium flour beetles: the rate of spread and effect on population size. AB - This paper reports on the effects of a cytoplasmically inherited reproductive incompatibility in different genetic strains of the flour beetle, Tribolium confusum. We measured the rate of spread and the effect of host population size using different initial frequencies of infection with a cytoplasmic factor that mediates reproductive incompatibility. There were two experiments, in one the infected and uninfected lines were from the same genetic strain, b-Yugoslavia. In the other, the infected line was from the "high cannibalism" bIV strain and the uninfected line from the "low cannibalism" bI strain. We estimate that the fitness ratio of infected to uninfected in b-Yugoslavia is 0.63 and the observed rate of spread for this strain corresponds to a model of cytoplasmic inheritance that takes into account the productivity differences between the infected and cured lines. In the bI-bIV experiment, because the uninfected and infected lines are from different genetic strains, we cannot partition the effects of the cytoplasmic factor from other factors. The rate of spread in the bI-bIV experiment is faster in males and slower in females than predicted from a model of cytoplasmic inheritance. In both experiments, productivity varies with initial infection frequency; however, the relationship is not explained by a simple model that predicts lower population size at intermediate infection frequencies. PMID- 2307359 TI - Genetic variation for sex ratio traits within a natural population of a parasitic wasp, Nasonia vitripennis. AB - By analyzing isofemale strains extracted from a natural population of Nasonia vitripennis, we detected variation for the sex ratios produced in fresh hosts (first sex ratios) and in previously parasitized hosts (second sex ratios). Under simple assumptions of population structure, this between-strain heterogeneity of first sex ratios results in heterogeneity of fitnesses. There is approximately ten percent difference in average fitnesses between the strains. (The fitnesses of second sex ratios are analyzed in the accompanying paper.) Average first and average second sex ratios are uncorrelated. There is significant between-female heterogeneity within some strains for first sex ratios but not for second sex ratios. In addition, the average direct-developing and diapause first sex ratios (but not second sex ratios) are significantly correlated. There are significant correlations between the direct-developing and diapause sex ratios produced by the same female. The strains differ in their effects on the sex ratio and size of another female's brood in the same host. Data on these types of variation for sex ratio traits are essential for further progress in the study of sex ratio evolution. PMID- 2307360 TI - The comparative biology of second sex ratio evolution within a natural population of a parasitic wasp, Nasonia vitripennis. AB - Correlation and regression analyses indicate that isofemale strains extracted from a population of the parasitic wasp, Nasonia vitripennis, differ in the fit of their second sex ratios (those produced in previously parasitized hosts) to the predictions of the theory of optimal facultative sex ratio adjustment. Under the theory's simple assumptions about population structure, there is significant heterogeneity of fitnesses among the isofemale strains. The reasons underlying these types of heterogeneity must be understood before we can make statements about the nature of sex ratio evolution in this species. These results suggest that comparative analyses are essential for testing the qualitative predictions of optimality models. PMID- 2307361 TI - Statistical genetics of an annual plant, Impatiens capensis. I. Genetic basis of quantitative variation. AB - Analysis of quantitative genetics in natural populations has been hindered by computational and methodological problems in statistical analysis. We developed and validated a jackknife procedure to test for existence of broad sense heritabilities and dominance or maternal effects influencing quantitative characters in Impatiens capensis. Early life cycle characters showed evidence of dominance and/or maternal effects, while later characters exhibited predominantly environmental variation. Monte Carlo simulations demonstrate that these jackknife tests of variance components are extremely robust to heterogeneous error variances. Statistical methods from human genetics provide evidence for either a major locus influencing germination date, or genes that affect phenotypic variability per se. We urge explicit consideration of statistical behavior of estimation and testing procedures for proper biological interpretation of statistical results. PMID- 2307362 TI - Statistical genetics of an annual plant, Impatiens capensis. II. Natural selection. AB - Measurement of natural selection on correlated characters provides valuable information on fitness surfaces, patterns of directional, stabilizing, or disruptive selection, mechanisms of fitness variation operating in nature, and possible spatial variation in selective pressures. We examined effects of seed weight, germination date, plant size, early growth, and late growth on individual fitness. Path analysis showed that most characters had direct or indirect effects on individual fitness, indicating directional selection. For most early life cycle characters, indirect effects via later characters exceed the direct causal effect on fitness. Selection gradients were uniform across the experimental site. There was no evidence for stabilizing or disruptive selection. We discuss several definitions of stabilizing and disruptive selection. Although early events in the life of an individual have important causal effects on subsequent characters and fitness, there is no detectable genetic variance for most of these characters, so little or no genetic response to natural selection is expected. PMID- 2307363 TI - The mitochondrial genome organization of a maize fertile cmsT revertant line is generated through recombination between two sets of repeats. AB - The mitochondrial genome (mtDNA) organization from a fertile revertant line (V3) derived from the maize cytoplasmic male sterile type T (cmsT) callus tissue culture has been determined. We report that the sequence complexity can be mapped on to a circular "master chromosome" of 705 kb which includes a duplication of 165 kb of DNA when compared to its male sterile progenitor. Associated with this event is also a 0.423-kb deletion, which removed the cmsT-associated urf13 gene. As found for the maize normal type (N) and cmsT mitochondrial genomes, the V3 master chromosome also exists as a multipartite structure generated by recombination through repeated sequences. PMID- 2307364 TI - DNA methylation in eukaryotes: kinetics of demethylation and de novo methylation during the life cycle. AB - We present a model for the kinetics of methylation and demethylation of eukaryotic DNA; the model incorporates values for de novo methylation and the error rate of maintenance methylation. From the equations, an equilibrium is reached such that the proportion of sites which are newly methylated equals the proportion of sites which become demethylated in a cell generation. This equilibrium is empirically determined as the level of maintenance methylation. We then chose reasonable values for the parameters using maize and mice as model species. In general, if the genome is either hypermethylated or hypomethylated it will approach the equilibrium level of maintenance methylation asymptotically over time; events occurring just once per life cycle to suppress methylation can maintain a relatively hypomethylated state. Although the equations developed are used here as framework for evaluating events in the whole genome, they can also be used to evaluate the rates of methylation and demethylation in specific sites over time. PMID- 2307365 TI - The opportunity for natural selection on multigene families. PMID- 2307366 TI - How much genetic variation can be maintained by genotype-environment interactions? PMID- 2307367 TI - Effect of inpatient psychiatry training on internal medicine residents. Results of a survey. AB - Forty-two residents in internal medicine completed an attitudinal survey at the beginning and end of a 2-month inpatient psychiatry rotation. Residents noted a significant increase in their confidence regarding the management of various psychiatric problems and personality problems, the conducting of supportive counseling, the making of psychiatric referrals, the usefulness of psychotherapy, and the ability to discuss emotionally difficult subjects with patients. The rotation was perceived as being worthwhile and enjoyable. Areas of uncertainty that remained included concern regarding the time demands, the perception that psychiatric patients are anxiety-provoking and difficult to treat, and that psychiatric knowledge was an extension of common sense. PMID- 2307368 TI - Development of an optically scanned consultation-liaison data base. AB - Every clinical service must record certain data about its patient care activities. In low-volume services, such as Psychiatric Inpatient Services, with perhaps 20-30 admissions per month, and an average patient stay of 2-4 weeks, a large amount of data on each patient can be obtained during the contact time with the patient. On the other hand, very large-volume psychiatric services, such as Emergency and Consultation-Liaison (C-L) Services, may not need or be able to gather such a large amount of data on every patient seen. This article describes the development of a brief, optically scannable, and computerized minimal data base form for patients seen by a very large division of C-L Psychiatry. The system is feasible and easily auditable for completeness and reliability. This data base has already served many important functions beyond providing an administrative statistical summary of services rendered. It is presented as a model for the development of similarly efficient data collection methods for other high-volume psychiatric services. PMID- 2307369 TI - Impact of psychiatric comorbidity on length of hospital stay in gastroenterology patients. AB - The impact of psychiatric comorbidity (PCM) on hospital length of stay (LOS) was prospectively examined in 110 patients admitted to a gastroenterology unit. Patients with and without PCM had a mean LOS of 8-9 days. Within the largest subgroup of medical diagnosis (peptic ulcer disease), patients with PCM had a mean LOS 2 days longer than those without PCM. The relationship between PCM and LOS varied substantially between physicians, suggesting their responses differ to patients who present psychiatric symptoms. PMID- 2307370 TI - A two-base change in a POU factor-binding site switches pituitary-specific to lymphoid-specific gene expression. AB - The structurally related POU homeo domain proteins Pit-1 and Oct-2 activate pituitary- and lymphoid-specific transcription, respectively, by binding to similar AT-rich motifs in their target genes. In this study we identify bases critical for recognition and activation by Pit-1 and examine how small differences in Pit-1 and Oct-2-binding sites can impart differential transcriptional responses in pituitary and B-lymphoid cells. Scanning mutagenesis of Pit-1 response elements in both the rat prolactin and growth hormone genes reveals a critical binding motif recognized in an identical manner by the native Pit-1 protein and cloned Pit-1 gene product. This motif, ATTATTCCAT, differs by only two bases from the octamer element, ATTTGCAT, required for Oct-2-dependent activation of immunoglobulin genes. Cross recognition of Pit-1 and Oct-2 sites by both factors can be demonstrated in competitive binding assays, in which an oligometric Pit-1 site from the prolactin gene is converted to an Oct-2 site by a double point mutation. In contrast to the binding data, no cross activation of transcription is detectable in cultured cell lines. When inserted immediately 5' to a prolactin TATA box, the wild-type prolactin element enhances transcription strongly in pituitary cells but is inactive in B cells, whereas the octamer variant of the prolactin site activates expression in B cells but is silent in pituitary lines. Both elements are nonfunctional in heterologous cell lines that lack Pit-1 and Oct-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307371 TI - The block to transcription elongation is promoter dependent in normal and Burkitt's lymphoma c-myc alleles. AB - Aberrant c-myc expression patterns occur in human Burkitt's lymphoma cells, which consistently exhibit c-myc chromosomal translocations, mutations within and flanking the translocated allele, a loss of the block to transcription elongation in exon 1, and a promoter shift to use of the upstream P1 promoter. To define the mechanism responsible for the loss of transcription elongation blockage and resulting c-myc deregulation in Burkitt's lymphoma, we analyzed transcription patterns after transfer of normal and Burkitt's lymphoma c-myc alleles into murine cells and Xenopus oocyte germinal vesicles. We have determined that although the mutations within and surrounding several Burkitt's lymphoma c-myc alleles are not sufficient, in themselves, to abrogate the transcription elongation block, transcription initiation from the P2 promoter may be necessary to obtain the block to transcription elongation. To test directly the role of c myc promoters in programming transcription elongation blockage, we analyzed transcription patterns from in vitro mutagenized c-myc genes containing deletions of either the P1 or P2 promoter. These data confirm that P1-initiated c-myc transcripts do not terminate at discrete sites near the 3' end of exon 1, whereas P2-initiated transcripts either terminate or read through the transcription block signals. Therefore, overexpression and/or constitutive expression from the c-myc P1 promoter may contribute to increased readthrough transcription in Burkitt's lymphoma cells and, hence, to aberrant expression patterns or levels of c-myc steady-state transcripts. In addition, the ability of normal cells to modulate c myc P2-initiated transcription to either read through or to block elongation provides a fine control mechanism over c-myc steady-state RNA levels. PMID- 2307372 TI - Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA. AB - The rat beta-tropomyosin gene encodes two isoforms, termed skeletal muscle beta tropomyosin and fibroblast last tropomyosim 1 (TM-1), via an alternative RNA processing mechanism. The gene contains 11 exons. Exons 1-5 and exons 8 and 9 are common to all mRNAs expressed from the gene. Exons 6 and 11 are used in fibroblasts, as well as smooth muscle, whereas exons 7 and 10 are used only in skeletal muscle. In the present studies we focused on the mutually exclusive internal alternative splice choice involving exon 6 (fibroblast-type splice) and exon 7 (skeletal muscle-type splice). We have identified two distinct elements in the intron, upstream of exon 7, involved in splice site selection. The first element is comprised of a polypyrimidine tract located 89-143 nucleotides upstream of the 3' splice site, which specifies the location of the lariat branchpoints used, 144-153 nucleotides upstream of exon 7. The 3' splice site AG dinucleotide has no role in selection of these branchpoints. The second element is comprised of intron sequences located between the polypyrimidine tract and the 3' splice site of exon 7. It contains an important determinant in alternative splice site selection, because deletion of these sequences results in the use of the skeletal muscle-specific exon in nonmuscle cells. We propose that the use of lariat branchpoints located far upstream from a 3' splice site may be a general feature of some alternatively excised introns, reflecting the presence of regulatory sequences located between the lariat branch site and the 3' splice site. The data also indicate that alternative splicing of the rat beta tropomyosin gene is regulated by a somewhat different mechanism from that described for rat alpha-tropomyosin gene and the transformer-2 gene of Drosophila melanogaster. PMID- 2307373 TI - When 'something is wrong': a case for investigating vague health complaints. AB - When a chronically ill elderly woman complained that she felt something was wrong, close attention and follow-up by physician and nursing home staff paid off. PMID- 2307374 TI - Salvage of Lisfranc's tarsometatarsal joint by arthrodesis. AB - Sixteen patients with fractures or fracture-dislocations of the tarsometatarsal (Lisfranc) joint who failed initial treatment were salvaged by arthrodesis using a technique of rigid internal fixation. Preoperative symptoms included local pain in all patients, progressive flatfoot deformity with forefoot abduction in 12 patients, and ankle or lateral impingement pain in five. The technique involved exposing the joint, denuding it of cartilage and scar, and reduction and fixation with lag screws. A total of 49 joints were fused. When significant deformity was present, reduction was performed before arthrodesis. Clinically symptomatic and radiographically proven nonunion occurred in four sites in three patients. One healed after revision. Good to excellent results were obtained in 11 patients (69%). Five patients had a fair or poor results. All but one of the patients were subjectively improved. Four patients were symptom free and returned to their preinjury lifestyles. Accurate reduction and early treatment had a significant positive relationship with outcome. Injuries that occurred in the workplace and those that incurred a long delay until treatment showed a significant negative correlation to outcome. Neither the age of the patient nor the number of joints fused had a significant impact on result. PMID- 2307375 TI - Keller's arthroplasty and Mitchell osteotomy: a comparison with first metatarsal osteotomy of the long-term results for hallux valgus deformity in the younger female. AB - We have made a retrospective comparison between the results of 37 Keller's arthroplasties and 36 distal transverse first metatarsal osteotomies performed in female patients between the ages of 25 and 50 years, for the treatment of hallux valgus. The choice of operation depended on the policy of the consultant responsible for treatment, but analysis of the preoperative findings showed that the two groups were similar, allowing comparative assessment of Keller's procedure in the younger middle-aged patient. All patients were assessed 3 to 5 years after operation using an objective scoring system of symptoms, clinical examination, anteroposterior standing radiographs and walking footprints from a Harris Beath mat. The results following a Keller's arthroplasty were excellent in 7 (19%), good in 22 (60%), poor in 6 (16%), and needed revision in 2 cases (5%). In the osteotomy group, 11 (30.5%) were excellent, 19 (52.5%) were good, 5 (14%) were poor, and 1 (3%) required revision. PMID- 2307376 TI - Subtalar arthrodesis in children with cerebral palsy: results using iliac bone plug. AB - Twenty-six extra-articular subtalar arthrodeses were performed on 15 patients with flexible planovalgus feet due to cerebral palsy. Following muscle balancing procedures, an iliac bone plug was used to stabilize the sinus tarsi. A review of the results up to 12 years, average 6.8, is presented. Overall satisfactory results were achieved in 88.4% of the patients, unsatisfactory in 11.6%. All children were immobilized in short-leg walking casts for 6 to 8 weeks. The surgical technique is described. The procedure gave good stability to the subtalar joint and was found to be reliable. Graft acquisition was simple and there were no complications. PMID- 2307377 TI - Foot growth in children age one to five years. AB - As part of the protocol on the Development of the Child's Arch, foot growth studies were monitored prospectively in 107 children from 1 year of age till 5 years of age. Under 15 months of age, growth necessitated a 1/2 size footwear change in less than 2 months; from 15 months to 2 years of age, 1/2 size increase occurred every 2 to 3 months; from 2 to 3 years of age, 1/2 size change every 3 to 4 months; and from 3 to 5 years of age, 1/2 size change every 4 months. Although foot growth in boys and girls is parallel, boys' feet tend to average one size longer and one size wider. Width growth remained proportional to length growth throughout the study. PMID- 2307378 TI - Normal magnetic resonance anatomy of the tarsal tunnel. AB - Images of five cadaver ankles and three normal volunteers were obtained in an attempt to delineate magnetic resonance (MR) anatomy of the tarsal tunnel. Multiplanar T1-weighted (TE 20 msec, TR 600 msec) scans were obtained of the cadaver specimens while T1 and T2 weighted (TE 20, 80 msec, TR 2000 msec) scans were obtained of the volunteer ankles. After imaging, the cadaver ankles were frozen, sectioned, photographed, and compared to the MR images in the transverse plane. The anatomical structures seen on the MR images correlated closely with the cadaver sections. The bony and soft tissue boundaries and contents of the tarsal tunnel could be imaged with detail easily sufficient to delineate all the major structures within it, including the posterior tibial nerve and its branches. PMID- 2307379 TI - Silastic implant arthroplasty with proximal metatarsal osteotomy for painful hallux valgus. AB - First metatarsophalangeal joint arthrosis may be associated with hallux valgus deformity. In an attempt to address the pain and deformities of this disorder, silastic implant arthroplasty combined with soft tissue balancing and proximal first metatarsal osteotomy has been performed on 17 feet in 11 patients. A retrospective review of the results at an average followup of 29.5 months is presented. Subjective pain relief has been satisfactory, and loss of correction of deformity has been minimal. Infection remains as a significant postoperative complication. This technique may be a treatment option in the low demand patient with a hallux valgus deformity, painful arthritis of the first metatarsophalangeal joint, and a wide first intermetatarsal angle. PMID- 2307380 TI - An anatomic study of subtalar instability. AB - Subtalar instability has been recognized as a cause of ankle symptoms. The purpose of this anatomic study is to determine the ligament damage required to produce subtalar instability, and to define a radiographic technique to demonstrate it. Ten fresh adult cadaver ankles were dissected. Selective sectioning of the calcaneofibular ligament, capsule, and interosseous ligaments of the subtalar joint were done. Radiographic documentation of subtalar opening was recorded, using a lateral and Brodan's view. Sectioning of the calcaneofibular ligament alone produced a 5-mm opening of the subtalar joint. When combined with sectioning of the interosseous ligament, a 7-mm opening was produced. This was reproduced with a plantar flexion-supination load to the foot. Instability of the ankle joint (talar tilting) was produced only when loading caused additional tearing of the anterior talofibular ligament. This study suggests that surgical repairs to correct lateral ankle instability should include repair or substitution of the calcaneofibular ligament if subtalar instability is a consideration. PMID- 2307381 TI - Use of isolated cold stress testing in determining normal lower extremity thermoregulation. AB - Isolated cold stress testing was performed on 72 healthy subjects in order to evaluate the normal thermoregulatory potential of vessel beds in the acral areas of the lower extremity. Two patterns of response were demonstrated: a cool response in approximately 80% of subjects, and a warm pattern in approximately 20%. In the former, the responses to cold stress were more active and the temperatures lower; in the latter, there was little change in temperature in response to the cold stress. Both patterns correlated strongly with initial temperature, and neither pattern correlated with age, sex, or smoking habits. No subjects reported pain, numbness, or discomfort during the test. This study demonstrated that wide variations in thermoregulatory flow were possible without clinical symptoms, and suggested that nutritional blood flow was adequate to meet metabolic demands despite thermoregulatory modulation. PMID- 2307382 TI - Fracture of the entire posterior process of the talus: a case report. AB - A 31-year-old man sustained a displaced fracture of the entire posterior process of the talus. Despite anatomic reduction and internal fixation, limitation of ankle and subtalar joint motion persisted at follow-up, 32 months after the injury. Great toe dorsiflexon was also limited, presumably from flexor hallucis longus tethering behind the ankle joint. The fracture healed without evidence of avascular necrosis of either the talar body or the posterior fragment. PMID- 2307383 TI - Leiomyosarcoma of the os calcis. AB - A primary leiomyosarcoma of the os calcis, occurring in a 68-year-old woman and treated by below-the-knee amputation, is reported. The diagnosis was confirmed by electron microscopy, and supported by immunochemistry. These techniques can be performed in a primary spindle cell osseous neoplasm to distinguish leiomyosarcoma from fibrosarcoma and malignant fibrous histiocytoma. A total of 28 cases of primary leiomyosarcoma of extragnathic bones have been reported in the literature with one occurring in the foot. This is the first reported case involving the os calcis and the first reported leiomyosarcoma of the foot in the English literature. PMID- 2307384 TI - Redirecting K-wires and Steinmann pins. PMID- 2307385 TI - [Extended application potential for Esser's speech-color image transformation in the phoniatrics clinic: initial report]. AB - The SFT system developed by Esser is an electronic device primarily used for visualizing speech sounds in the therapy of severely hearing-impaired patients. This paper discusses first results in the diagnostic and therapeutic application of the SFT on persons with no hearing handicap. The range of application includes the articulation, its malfunctions, speech coordination and voice functions. Observations have shown that SFT representation supplementary to listener judgement permits a clear description of a series of features from the categories mentioned above. Phonetic disorders, speech coordination and certain voice functions can thus also be compared and documented directly. Its application as an optical feedback device in the course of articulatory and voice therapy as well as the adjustment of the SFT system to certain fields of application are discussed. PMID- 2307386 TI - Information processing, cognition, attention, and communication following closed head injury. PMID- 2307387 TI - Voice disorders among players of wind instruments? PMID- 2307388 TI - Consideration of the relationship between the fundamental frequency of phonation and vocal jitter. PMID- 2307389 TI - [The evaluation of stroboscopic criteria]. AB - The evaluation of stroboscopic findings and their comparison require the utmost experience of the examiner. Methods leading towards a more objective evaluation have been published but are not yet available in many phoniatric departments as routine procedures and can also fail as in the case of the mucosal wave for example. A procedure for judging each stroboscopic criterion separately is presented in this paper, the criteria being symmetry (symmetry of movement, synchronism), amplitudes, mucosal wave, vibratory closure (sufficiency, duration) and special findings such as aperiodic vibrations or longitudinal waves. For most of these criteria an index can be given thus making possible quasi-statistical calculations as long as the examination is performed by the same person. PMID- 2307390 TI - [Atypical forms of syringomyelia--a case report]. AB - The introduction of magnetic resonance imaging (MRI) has made the diagnosis of syringomyelia safer and more exact. Moreover, the lack of correlation between the clinical picture and the MRI findings was demonstrated, and unsuspected cases could be identified as pertaining to syringomyelia. The three cases reported should point at the variable symptomatology in syringomyelia. A more frequent occurrence of unusual symptoms and courses of the disease than previously assumed is discussed. PMID- 2307391 TI - Sequence of prolactin effects on phospholipid synthesis in mouse mammary gland explants. AB - In cultured mouse mammary gland explants derived from 12-14 day pregnant mice, the effect of prolactin (PRL) on the rate of incorporation of several precursors into neutral lipids and phospholipids was determined. Employing [14C]-acetate as a substrate, PRL stimulates its incorporation into a) neutral lipids by 4-6 hours, b) phosphatidyl choline (PC) and phosphatidyl inositol-phosphatidyl serine (PI-PS) by 1-2 hours, and c) phosphatidyl ethanolamine (PE) by 2-4 hours. Using [3H]-glycerol as a substrate, the temporal response to PRL for its incorporation into the neutral lipids was the same as that for [14C]-acetate, however, PRL did not enhance the rate of [3H]-glycerol incorporation into the phospholipids at any time through 16 hours. PRL similarly had no effect on the rates of [3H]-choline, [3H]-serine, [3H]-ethanolamine, or [32P]O4 incorporation into the phospholipids at hormone exposure periods of 8 hours or more. And finally, PRL had no effect on the rates of [3H]-arachidonate or [14C]-linoleate incorporation into neutral lipids or phospholipids at culture periods up to 18 hours. These data suggest that the early effect of PRL on [14C]-acetate incorporation into the phospholipids is due to either the insertion of newly synthesized fatty acids and/or the extension of fatty acids contained in the phospholipids. PMID- 2307392 TI - Human pancreatic polypeptide in children and young adults. AB - Measurement of human pancreatic polypeptide may be useful for assessment of gastrointestinal function, integrity of the parasympathetic nervous system or screening for endocrine neoplasia. In adults hPP levels have been reported to increase with age. However hPP levels throughout childhood have not been well characterized in comparison with the adult range. We studied fasting human pancreatic polypeptide (hPP) from 45 pediatric patients, from infancy - 15 years, and 18 older adolescents and adults aged 16-45 years. The mean hPP level of children (233 +/- 147 pg/ml) was significantly higher than that (113 +/- 35 pg/ml) of adults (P less than .0001). There was no difference in mean hPP levels of children with normal growth hormone secretion compared to growth hormone deficient patients. There was no effect of gender or body mass index on hPP levels. We conclude that fasting hPP levels must be interpreted with respect to the age of the subject, children particularly, in that preteens may have higher fasting levels than older teenagers and adults. PMID- 2307393 TI - Behaviour and physiology of castrated rats with different episodic schedules of testosterone restoration. PMID- 2307394 TI - Orthotopic liver transplantation for alcoholic liver disease. AB - Alcohol abuse is the most common cause of end-stage liver disease in the United States, but many transplant centers are unwilling to accept alcoholic patients because of their supposed potential for recidivism, poor compliance with the required immunosuppression regimen and resulting failure of the allograft. There is also concern that alcohol-induced injury in other organs will preclude a good result. From July 1, 1982, to April 30, 1988, 73 patients received orthotopic liver transplants at the University of Pittsburgh for end-stage alcoholic liver disease. Fifty-two (71%) of these were alive at 25 +/- 9 mo (mean +/- S.D.) after transplantation, when a phone survey of these patients, their wives/husbands, and their physicians was performed to evaluate their subsequent use of alcohol, current medical condition and employment. Data obtained were compared with those for nonalcoholic patients selected as transplant controls. The recidivism rate has been 11.5%, with most patients drinking only socially. Fifty-four percent of the survivors are employed, 21% classify themselves as homemakers and only 11 (21%) are unable to work. Twenty-one patients died after transplantation; the most frequent cause of death was sepsis (43%), and intraoperative death was the next most common cause (28.6%). These data demonstrate that alcoholic patients can be transplanted successfully and achieve good health not significantly different from that of individuals transplanted for other causes. Thus orthotopic liver transplantation is a therapeutic option that should be considered for individuals with end-stage alcoholic liver disease who desire such therapy. PMID- 2307395 TI - S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. AB - Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S-adenosyl-L-methionine concentration: 74.6 +/- 2.4 nmol/gm vs. 108.9 +/- 8.2 nmol/gm liver in controls (p less than 0.005). The depletion was corrected with S-adenosyl-L-methionine (0.4 mg/kcal) administration (102.1 +/- 15.4 nmol/gm after S-adenosyl-L methionine-ethanol, with 121.4 +/- 11.9 nmol/gm in controls). Ethanol also induced a depletion of glutathione (2.63 +/- 0.13 mumol/gm after ethanol vs. 4.87 +/- 0.36 mumol/gm in controls) that was attenuated by S-adenosyl-L-methionine (3.89 +/- 0.51 mumol/gm in S-adenosyl-L-methionine-methanol vs. 5.22 +/- 0.53 mumol/gm in S-adenosyl-L-methionine controls). There was a significant correlation between hepatic S-adenosyl-L-methionine and glutathione level (r = 0.497; p less than 0.01). After the baboons received ethanol, we observed the expected increase in circulating levels of the mitochondrial enzyme glutamic dehydrogenase: 95.1 +/- 21.4 IU/L vs. 13.4 +/- 1.8 IU/L; p less than 0.001, whereas in a corresponding group of animals given S-adenosyl-L-methionine with ethanol, the values were only 30.3 +/- 7.1 IU/L (vs. 9.6 +/- 0.7 IU/L in the S adenosyl-L-methionine controls). This attenuation by S-adenosyl-L-methionine of the ethanol-induced increase in plasma glutamic dehydrogenase (p less than 0.005) was associated with a decrease in the number of giant mitochondria (assessed in percutaneous liver biopsy specimens), with a corresponding change in the activity of succinate dehydrogenase, a mitochondrial marker enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307396 TI - Sensitization of hepatic lipocytes by high-fat diet to stimulatory effects of Kupffer cell-derived factors: implication in alcoholic liver fibrogenesis. AB - A high-fat diet has previously been shown to be a key factor for induction of alcoholic liver fibrosis in a rat model of intragastric ethanol infusion. To explore a possible mechanism by which the high-fat diet facilitated such an effect, the present study examined how the high-fat diet with or without ethanol affected proliferation and collagen formation of hepatic lipocytes, perisinusoidal cells that have been suggested to be involved in liver fibrogenesis. We also evaluated effects of the high-fat diet on the sensitivity of lipocytes to stimulatory effects of Kupffer cell-derived factors. Intragastric infusion of ethanol and the high-fat diet for 9 to 10 wk resulted in induction of a varying degree of perivenular fibrosis in 75% of animals. Lipocytes isolated from these animals (A) had significantly higher basal rates of proliferation (three to four times) and collagen formation (1.5 times) than those isolated from control animals, which were isocalorically infused with the high-fat diet (H) or the low-fat diet (L), or those that were fed chow ad libitum (C). Lipocytes from the H group exhibited significantly higher relative production of collagen than those from the L group, but their net collagen production was not enhanced. The dialyzed Kupffer cell-conditioned medium from the A group markedly stimulated proliferation and collagen formation of lipocytes from the groups given the high fat diet (A and H) but had minimal effects on those from the L and C groups, establishing the order of decreasing lipocyte sensitivity from the A, H, L to C group. Similarly, lipocytes from the H and A groups exhibited a more profound responsiveness to the stimulatory effect of transforming growth factor beta 1 on collagen formation. These results demonstrate (a) that lipocytes isolated from the rats given the high-fat diet and ethanol are markedly proliferative and produce more collagen; and (b) that the Kupffer cells derived from these animals release factors that stimulate proliferation and collagen formation of lipocytes and (c) that the high-fat diet sensitizes lipocytes for stimulatory effects of the Kupffer cell-derived factors and transforming growth factor beta 1. PMID- 2307397 TI - Role of endotoxin-responsive macrophages in hepatic injury. AB - Although administration of 100 mg galactosamine caused severe hepatic injury in C3H/HeN mice, splenectomy reduced the grade of this hepatotoxicity. However, this hepatic injury was scarcely detected in the endotoxin-resistant C3H/HeJ mice. In addition, in contrast to high lethality in C3H/HeN mice with a combined administration of galactosamine and endotoxin, splenectomy rendered C3H/HeN mice slightly resistant to this treatment. Further resistance was demonstrated in C3H/HeJ mice. In an attempt to clarify the role of endotoxin-responsive spleen cells in the pathogenesis of hepatic injury, we investigated galactosamine induced hepatic injury by transfer of lipopolysaccharide-treated C3H/HeN or C3H/HeJ spleen cells. Both oxygen-derived free radical production and the proportion of macrophages in spleen cells were markedly enhanced in C3H/HeN mice after an intraperitoneal injection of lipopolysaccharide. Further increase in oxidative free radical production was found in the dish-adherent cells (macrophages). These enhancements were not demonstrated in lipopolysaccharide treated C3H/HeJ spleen cells. Although hepatic injury was not demonstrated in both C3H/HeN and C3H/HeJ mice treated with 35 mg galactosamine alone, severe hepatotoxicity was found in these galactosamine-treated mice when they received lipopolysaccharide-activated C3H/HeN spleen cells, especially macrophages. Simultaneous administration of superoxide dismutase with the activated spleen cells reduced the grade of hepatic injury. On the other hand, hepatic injury was not demonstrated in the galactosamine-treated C3H/HeN or C3H/HeJ mice when they received lipopolysaccharide-treated C3H/HeJ spleen cells, although 3H galactosamine incorporation into hepatocytes was nearly identical in both C3H/HeN and C3H/HeJ mice. These results suggest that oxidative free radicals of lipopolysaccharide-responsive macrophages could contribute to the pathogenesis of galactosamine-induced hepatic injury. PMID- 2307398 TI - N-acetylglucosamine-6-phosphate deacetylase in hepatocytes, Kupffer cells and sinusoidal endothelial cells from rat liver. AB - The activity of N-acetylglucosamine-6-phosphate deacetylase, a key enzyme in the pathway of N-acetylglucosamine catabolism, was measured in hepatocytes, Kupffer cells and sinusoidal endothelial cells from rat liver and cultured human skin fibroblasts. Kupffer cells and endothelial cells had similar high levels of deacetylase activity that were more than twice the level observed in fibroblasts. In contrast, hepatocytes had extremely low activity (several hundredfold less than Kupffer cells and endothelial cells). A major implication of deacetylase deficiency in hepatocytes is that N-acetylglucosamine generated as a result of the catabolism of complex carbohydrates in these cells cannot enter glycolysis and must be largely reused for the synthesis of plasma glycoproteins and other N acetylglucosamine-containing macromolecules. PMID- 2307399 TI - The effect of liver dysfunction on colchicine pharmacokinetics in the rat. AB - Recent work has shown that colchicine may benefit patients with primary biliary or alcoholic cirrhosis. However, very little is known about its pharmacokinetics in the presence of impaired liver function. To study this we examined the effects of three models of experimental liver dysfunction and one of cytochrome P-450 inhibition on colchicine elimination in the rat. The models of experimental liver dysfunction included bile duct ligation (with sham-operated controls), alpha naphthylisothiocyanate-induced intrahepatic cholestasis and galactosamine-induced diffuse hepatocellular necrosis. The control group had a colchicine clearance of 77.33 ml/min.kg +/- 8.27 ml/min.kg, a half-life of 16.68 min +/- 0.97 min and a volume of distribution of 1.84 L/kg +/- 0.15 L/kg. Cimetidine administration, 120 mg/kg intraperitoneally 15 min before colchicine administration, caused clearance to decrease by 32% (p less than 0.05) and half-life to increase by 38% (p less than 0.05). Volume of distribution did not change. At 48 hr after bile duct ligation, colchicine clearance decreased by 84% (p less than 0.05), terminal half life increased to 513.7 min +/- 106.6 min (p less than 0.05) and volume of distribution increased by 175% (p less than 0.05). Colchicine pharmacokinetics in sham-operated rats were not statistically different from the above mentioned controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307400 TI - Inactivation and dissociation of S-adenosylmethionine synthetase by modification of sulfhydryl groups and its possible occurrence in cirrhosis. AB - Catalytically active human and rat liver S-adenosylmethionine synthetase exists mainly in tetramer and dimer form. In liver biopsy samples from cirrhotic patients a marked reduction in total S-adenosylmethionine synthetase activity and a specific loss of the tetrameric form of the enzyme exist. We have investigated the possible role of sulfhydryl groups in maintaining the structure and activity of S-adenosylmethionine synthetase. Both forms of S-adenosylmethionine synthetase are rapidly inactivated by N-ethylmaleimide, and the loss of enzyme activity correlates with the incorporation of approximately 2 moles N-ethylmaleimide per mole of subunit. In addition, reaction with N-ethylmaleimide resulted in displacement of the tetramer-dimer equilibrium of the enzyme toward the dimer, but no monomer was detected under these conditions. A catalytically active monomeric S-adenosylmethionine synthetase was detected in the cytosolic extract from a liver biopsy sample from a cirrhotic patient, supporting our model for the structure of S-adenosylmethionine synthetase. Because treatment of S adenosylmethionine synthetase with N-ethylmaleimide resembles the situation of this enzyme in cirrhotic patients, it is proposed that impaired protection of the enzyme from oxidizing agents caused by a decreased synthesis of glutathione can explain the diminished synthesis of S-adenosylmethionine in liver cirrhosis. PMID- 2307401 TI - Enhancement of portal pressure reduction by the association of isosorbide-5 mononitrate to propranolol administration in patients with cirrhosis. AB - This study investigated whether oral doses of isosorbide-5-mononitrate, a preferential venous dilator that decreases portal pressure, could enhance the effects of propranolol on portal hypertension. Taking part in the study were 28 patients with cirrhosis and portal hypertension. Twenty patients (group 1) had hemodynamic measurements in baseline conditions after beta-blockade by intravenous administration of propranolol and after receiving oral doses of isosorbide-5-mononitrate. The remaining eight patients (group 2) were given oral isosorbide-5-mononitrate while receiving chronic propranolol therapy. In group 1, propranolol significantly reduced portal pressure (estimated as the gradient between wedged and free hepatic venous pressures) from 21.5 +/- 3.9 to 18.6 +/- 4.2 mm Hg (-13.7%, p less than 0.001), azygos blood flow (-38%, p less than 0.001), hepatic blood flow (-12.8%, p less than 0.05), cardiac output (-24.5%, p less than 0.001) and heart rate (-18.4%, p less than 0.001) without significant changes in mean arterial pressure. Addition of oral isosorbide-5-mononitrate caused a further and marked fall in portal pressure (to 15.7 +/- 3.1 mm Hg, p less than 0.001), without additional changes in azygos blood flow but with significant additional reductions in hepatic blood flow (-15.5%, p less than 0.05), cardiac output (-11.5%, p less than 0.001) and mean arterial pressure ( 22%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307402 TI - Hemodynamic evaluation of molsidomine: a vasodilator with antianginal properties in patients with alcoholic cirrhosis. AB - Organic nitrates were reported to reduce portohepatic venous pressure gradient in patients with cirrhosis. However, these drugs lower arterial pressure and are well known to induce tolerance. The aim of the present study was to assess the hemodynamic effects of molsidomine, an antianginal agent, which does not induce tolerance and has little effect on arterial pressure in patients with normal liver, in 13 patients with alcoholic cirrhosis. Wedged hepatic vein pressure ( 11%, p less than 0.01), portohepatic venous pressure gradient (-15%, p less than 0.005), hepatic blood flow (-17.4%, p less than 0.005), mean arterial pressure ( 13.5%, p less than 0.01) and cardiac output (-17%, p less than 0.001) were significantly reduced by molsidomine. Free hepatic vein pressure, intrinsic hepatic clearance indocyanine green, heart rate and systemic vascular resistances were not significantly modified. There was no correlation between the decrease in portohepatic venous pressure gradient and the reduction in mean arterial pressure on one hand and the decrease in cardiac output on the other hand. We therefore conclude that in patients with cirrhosis, molsidomine has effects similar to nitrates on systemic and splanchnic hemodynamics. PMID- 2307403 TI - Volume regulation in liver: further characterization by inhibitors and ionic substitutions. AB - The present study has been performed to elucidate the mechanisms of volume regulation in isolated perfused liver. Reduction of extracellular osmolarity by 80 mOsm/L leads to a release of potassium and a sustained alkalinization of effluent. Reexposure to isotonic perfusate leads to reuptake of potassium by the liver and acidification of effluent. Part of the alkalinization could be due to release of bicarbonate parallel to potassium release. Carboanhydrase inhibition and replacement of bicarbonate/CO2 by HEPES buffer, however, do not significantly modify volume regulatory potassium release or reuptake. Reduction of perfusate chloride to 37 mmol/L by replacement of NaCl with raffinose leads to a decrease of liver weight indicative of shrinkage of liver cells. Subsequent omission of 180 mmol/L raffinose leads to potassium and chloride release and to alkalinization of effluent. Volume regulatory release of potassium is impaired in 1 mmol/L quinidine, 1 mmol/L SITS and 5 mmol/L barium. Volume regulatory reuptake of potassium is impaired by 1 mmol/L amiloride. Volume regulatory release of potassium is not appreciably affected by either; 1 mmol/L furosemide, 1 mumol/L verapamil, 1 mmol/L amiloride or 1 mmol/L barium and volume regulatory potassium reuptake proved insensitive to 1 mmol/L furosemide or 1 mmol/L barium. The data suggest that the cells release potassium and chloride during regulatory volume decrease by quinidine, SITS and weakly barium-sensitive transport systems and that regulatory volume increase is accomplished by activation of Na/H exchange. PMID- 2307404 TI - Unusual trihydroxy bile acids in the urine of patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and those with cirrhosis. AB - Urinary bile acids from 20 patients treated with chenodeoxycholate, 18 treated with ursodeoxycholate, 15 treated with rifampicin and 8 patients with advanced cirrhosis were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. Occurrence rates and amounts of three so-called unusual trihydroxy bile acids, hyocholate, ursocholate and omega-muricholate, were increased in patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and decreased in cirrhotic patients as compared with those in untreated healthy adults. These data suggest that chenodeoxycholate and ursodeoxycholate are hydroxylated to produce unusual trihydroxy bile acids in bile acid-loaded humans and that this metabolism may be related to the induction of hepatic microsomal enzymes by rifampicin. In contrast, the hydroxylation of chenodeoxycholate and ursodeoxycholate may be impaired by severe hepatic damage. Because the urine is a secretory pathway for internal bile acids, the occurrence of unusual trihydroxy bile acids in the urine may be used as an indicator of hepatic ability to metabolize "hydrophobic" dihydroxy bile acids to their secretory forms. PMID- 2307405 TI - Role of cholecystokinin and the cholinergic system in intestinal stimulation of gallbladder contraction in man. AB - To determine the role of cholecystokinin and the cholinergic system in intestinal stimulation of gallbladder contraction, we studied the effects of atropine on plasma cholecystokinin and gallbladder contraction in six healthy volunteers (four men and two women aged 20 to 27 yr). Effects were noted after intraduodenal fat instillation and after dosage with exogenous cholecystokinin inducing plasma cholecystokinin concentrations similar to those after intraduodenal fat instillation. At regular intervals before and after administration of each stimulus, plasma cholecystokinin concentrations and gallbladder volumes were measured by radioimmunoassay and real-time ultrasonography, respectively. Intraduodenal infusion of 250 ml 20% Intralipid induced a peak plasma cholecystokinin increment of 10.2 +/- 1.6 pmol/L compared with 10.7 +/- 0.7 pmol/L during infusion of 1 Ivy dog unit per kilogram per hour of cholecystokinin. The increases in plasma cholecystokinin after fat and exogenous cholecystokinin administration were accompanied by similar decreases in gallbladder volume. Integrated gallbladder contraction after fat instillation was 3,939% +/- 288%.min compared with 3,301% +/- 359%.min during cholecystokinin infusion (NS). Atropine (0.015 mg/kg as bolus followed by 0.005 mg/kg/hr) did not change plasma cholecystokinin concentrations but induced similar inhibition of gallbladder contraction to 2,296% +/- 511%.min (p less than 0.05) after intraduodenal fat instillation and to 1,756% +/- 456%.min (p less than 0.05) during cholecystokinin infusion. We conclude that cholecystokinin is of major importance in intestinal stimulation of gallbladder contraction. Atropine inhibits the gallbladder response to intraduodenal fat. This inhibition is not due to a reduction in cholecystokinin secretion but to a diminished gallbladder response to cholecystokinin. PMID- 2307406 TI - Molecular characterization of a new variant of hepatitis B virus in a persistently infected homosexual man. AB - Based on the diversity of nucleotide sequences of cloned hepatitis B virus DNA genomes, we have predicted possible replication of genetic variants of human hepatitis B virus. This prediction is exemplified by studies of a chronic carrier of HBsAg/adw2, who lacked anti-HBc but carried exceedingly high levels of hepatitis B virus DNA in serum. Molecular characterization of a number of clones revealed a restriction map that deviated significantly from the typical pattern of the adw2 subtype, especially around the EcoRI site commonly used as a reference point. Mutations appearing consistently in the precore and core regions included (a) mutation in the precore region resulting in a termination codon after the initiation codon, (b) mutation of the core initiation codon and (c) an inframe insert of 36 nucleotides in the precore region with a new initiation site for the core protein. The 36-nucleotide insertion resulted in a new core protein with 12 extra amino acids at its amino-terminal end. A few scattered point mutations were clustered in the amino-terminal half of the core gene. Although the core protein of this hepatitis B virus variant carried immunologically detectable HBcAg, the absence of a humoral immune response to HBcAg could have been caused by previous infection with human immunodeficiency virus. This naturally occurring human hepatitis B virus variant replicated efficiently without expressing the precore region, confirming previous observations made of the artificial mutants of duck hepatitis B virus. PMID- 2307407 TI - Increase in hepatocyte and nuclear volume and decrease in the population of binucleated cells in preneoplastic foci of rat liver: a stereological study using the nucleator method. AB - Gamma-glutamyltranspeptidase-positive hepatocyte foci were produced in female rats given a single dose of diethylnitrosamine neonatally after birth and, after weaning, a diet containing phenobarbitone for 30 wk. The nucleator method, a new stereological approach, provided an efficient, unbiased estimate of mean cell volume in focal lesions and extrafocal areas. It also provided an unbiased sample of cells to estimate hepatocyte nuclear volume and the percentage of binucleated cells. The results showed an increase in the mean volume of mononucleated cells- from 4,700 micron3 in extrafocal areas to 12,700 micron2 in foci--and of binucleated cells--from 6,900 micron3 to 25,000 micron3. This demonstrated the hypertrophic effect of the carcinogenic treatment in focal lesions. A striking reduction in the proportion of binucleated cells was also observed in the preneoplastic lesions. Nuclear volume measurements from mononucleated and binucleated hepatocytes were used to assess ploidy. An apparent increase in nuclear ploidy, with no change in cellular ploidy, was noted in focal tissue when compared with nonfocal tissue. This appeared to be caused by an increase in mononucleated tetraploid cells and a reduction in binucleated cells with two diploid nuclei, indicating an altered mitotic mechanism in focal lesions. The significance of these changes in cell volume, apparent ploidy levels and binuclearity in preneoplastic foci is discussed in relation to the hepatocarcinogenic process. PMID- 2307408 TI - Should patients with end-stage alcoholic liver disease have a new liver? PMID- 2307409 TI - Histogenesis of vascular spiders. PMID- 2307410 TI - Multiple atypical adenomatous hyperplasia of type II pneumonocytes and bronchiolo alveolar carcinoma. PMID- 2307411 TI - Dysplastic naevi. PMID- 2307412 TI - Sarcomatoid carcinoma mimicking sarcoma. PMID- 2307413 TI - Pulmonary endocrine cells in hypertensive pulmonary vascular disease. AB - A study was made of the number of pulmonary endocrine cells, immunoreactive for gastrin-releasing peptide (bombesin) or calcitonin, in the terminal bronchioles of 39 cases of pulmonary vascular disease. In 25 of these, the form of vascular disease was plexogenic pulmonary arteriopathy, primary in 12 and secondary in 13, while the remaining 14 subjects had a wide range of other varieties of hypertensive pulmonary vascular disease. We found that pulmonary endocrine cells, especially those containing bombesin, were increased in number in both the primary and secondary forms of plexogenic pulmonary arteriopathy but not in other varieties of pulmonary hypertension. The prominent bombesin-containing cells were found in cases with cellular plexiform lesions but occurred even more prominently at an earlier stage when vascular smooth muscle cells were migrating from the inner media into the intima. PMID- 2307414 TI - Mucins in prostatic carcinoma. AB - Mucin production by prostatic carcinomas is not unusual and the identification of acidic mucin with an appropriate stain may be a useful adjunct in routine diagnostic surgical pathology. In our series of 53 cases of prostatic carcinoma, 20 (38%) showed significant acidic mucin production. This may allow differentiation from benign, hyperplastic tissues which produce neutral mucins only. A case of colloid carcinoma of prostate is described which satisfies Elbadawi's criteria for this uncommon variant. Some suggestions are made which, if rigorously applied, will permit the recognition of genuine cases of colloid carcinoma and of the prognostic significance of mucin-rich tumours. PMID- 2307415 TI - Basement membrane continuity in benign, premalignant and malignant epithelial conditions of the uterine cervix. AB - The pattern of basement membrane deposition in the uterine ectocervix was assessed in benign, premalignant and malignant conditions, using an indirect immunoperoxidase technique to detect laminin, an intrinsic basement membrane component. A semi-quantitative approach was used to assess the frequency of small breaks in the basement membrane. The cervical squamous epithelium in benign epithelial conditions has an almost completely continuous basement membrane, but the development of viral atypia or cervical intraepithelial neoplasia (CIN) is associated with the appearance of small basement membrane breaks. There is a correlation between increasingly severe CIN and increasing numbers of breaks, and there is a concurrent increase in the numbers of subepithelial inflammatory cells. The development of invasive neoplasm is associated with a sudden change to a fragmented pattern of basement membrane deposition, a finding which is of potential diagnostic use. PMID- 2307416 TI - Ultrastructural localization of extracellular matrix proteins in liver biopsies using ultracryomicrotomy and immuno-gold labelling. AB - We describe a technique for the localization of extracellular matrix proteins in wedge and needle biopsy specimens of human liver. Using ultra-thin (50-70 nm) sections of puncture perfusion fixed tissue, extracellular matrix proteins were localized using a protein A-gold labelling procedure. We obtained good preservation of ultrastructural detail and specific labelling for collagen types I, III and IV and fibronectin. The method represents a sensitive means of identifying the extracellular distribution and the cellular origin of these proteins in normal and diseased human liver. PMID- 2307417 TI - Parosteal osteogenic sarcoma of the hand. AB - Osteosarcomas of the tubular bones of the hands and feet are rare tumours and the initial biopsies are frequently misdiagnosed. We report a case of parosteal osteosarcoma arising in the metacarpal of a female patient aged 53 at first presentation. The tumour recurred three times over two decades and eventually metastasized to the lungs. The differential diagnosis includes florid reactive mesenchymal proliferation and bizarre parosteal osteochondromatous proliferations of the tubular bones of the hand. PMID- 2307418 TI - Immunosuppression and thrombosis in renal transplantation: an immunohistological study. AB - Renal biopsies were taken from 42 patients at seven and 21 days after renal transplantation. Paraffin sections from these specimens were examined immunocytochemically for the presence of platelet microthrombi in glomerular capillaries using the monoclonal antibody Y2/51. Patients were treated by one of four different immunosuppressive regimes, three of which included cyclosporin A, either alone or in combination with steroids and azathioprine. Microthrombi were detected in approximately 30% of biopsies and were much commoner in patients receiving multi-drug therapy. We conclude that, contrary to previous suggestions, glomerular capillary thromboses are not frequent in patients on cyclosporin A alone. They are found mainly in patients on multiple drug therapy, particularly when steroids are included. The detection of microthrombi is unlikely to be of assistance in the earlier detection of cyclosporin toxicity. PMID- 2307419 TI - Epithelioid angiomatosis in the acquired immunodeficiency syndrome: morphology and differential diagnosis. AB - A rare vascular proliferation found as a skin lesion in patients suffering from the acquired immunodeficiency syndrome and sometimes referred to as epithelioid angiomatosis is believed to be a manifestation of infection by the cat scratch bacillus or a related organism. We describe the histological findings from eight lesions seen in two cases. In all cases the diagnosis could be confirmed by demonstration within the lesions of groups of gram-negative rod-shaped organisms staining positively with the Warthin-Starry stain. This condition needs to be distinguished from a variety of reactive and neoplastic vascular proliferations. PMID- 2307420 TI - Broad ligament mucinous cystadenoma of borderline malignancy. PMID- 2307421 TI - The histopathology of 36 cases of plexogenic pulmonary arteriopathy. AB - A detailed histopathological study was made of the lungs of 36 cases of plexogenic pulmonary arteriopathy coming to combined heart-lung transplantation. It revealed two dissimilar processes involved in the pathogenesis of this disease. One comprised histological appearances consistent with constriction of muscular pulmonary arteries, a condition that would be likely to be reversed by pulmonary vasodilators. The other was the proliferation of myofibroblasts in the intima and lumen of pulmonary arteries, a disorder of growth unlikely to be influenced by this type of therapy. In previous ultrastructural studies we have shown that the source of these cells of muscular pedigree is muscle cells from the inner half of the media which migrate into the intima through gaps in the inner elastic lamina. In the present study we found a similar proliferation of myofibroblasts in the intima, not only of pulmonary arteries, but also of pulmonary veins, in plexogenic pulmonary arteriopathy. Arterial thrombi found were considered to be a complication rather than a cause of plexogenic pulmonary arteriopathy. Siderophages, cholesterol granulomas and focal fibrosis in the lung were considered to be a consequence of intrapulmonary haemorrhage early in the course of the disease. It is concluded that, while plexogenic pulmonary arteriopathy has an important vasoconstrictive element, it is also based on a disorder of growth of cells of muscular pedigree. This view has clear implications for the therapy of primary plexogenic pulmonary arteriopathy. PMID- 2307422 TI - Follicular myometritis: a previously undescribed component of pelvic inflammatory disease. PMID- 2307423 TI - The appendix as a 'skip lesion' in ulcerative colitis. PMID- 2307424 TI - Alveolar soft part sarcoma of the uterus. PMID- 2307425 TI - Adenomyoma of the stomach presenting as an antral polyp. PMID- 2307426 TI - Hospital supply expenses up 28.2% since 1984. PMID- 2307427 TI - Hospital prenatal care programs are an ounce of prevention. AB - The lack of adequate prenatal care exacts a high price from our nation's infants and hospitals. Reports put this as a cause of approximately two-thirds of infant deaths. And a significant percentage of hospitals' uncompensated care bills are the result of care delivered to mothers and their infants. However, health care executives in a number of communities have devised some unique programs to improve women's access to high-quality prenatal care. PMID- 2307428 TI - Systems fight uphill battle to gain physician loyalty. AB - Being part of a multihospital system has distinct advantages for physicians. But parlaying these advantages into physician loyalty to the system is difficult. To strengthen their relationships with physicians, some systems try to involve physicians in more management decisions. But system executives report that it's an uphill battle. PMID- 2307430 TI - Employee orientations should stress core values. PMID- 2307429 TI - Transfer centers save lives, minimize bad debt. AB - Tampa (FL) General Hospital is one of a handful of hospitals around the country that has set up transfer centers to resolve inappropriate-transfer problems. Hospital executives say that such centers save lives by coordinating transfers through a central point, and that they have reduced incidents of patients dumping by allowing only medically appropriate transfers. PMID- 2307431 TI - Automation: the key to lab profitability. PMID- 2307432 TI - Is competition driving CEOs out of health care? PMID- 2307433 TI - Expert discusses trauma care. PMID- 2307434 TI - Using credit as a marketing tool. PMID- 2307435 TI - Screening builds in safety for pet visits. PMID- 2307436 TI - UR oversight may ease provider woes. PMID- 2307437 TI - A plan for rewarding physician commitment. PMID- 2307438 TI - The autopsy: a professional obligation dissected. PMID- 2307439 TI - Medical uncertainty and the autopsy: occult benefits for students. AB - The autopsy has been of great importance in educating students regarding medical uncertainty. The marked decline in the use of the autopsy in medical education and continuing education has contributed significantly to the current discomfort among physicians regarding medical uncertainty and medical errors, which, in turn, has furthered the decline of the autopsy. Inordinate guilt, denial, and other defensive behaviors that many physicians marshall in response to uncertainty and error prevent these individuals from learning from their mistakes. The autopsy experience during medical school, properly utilized, helps students to confront fallibility and sets the stage for later successful management of uncertainty and error. PMID- 2307440 TI - An unintentional irony: the autopsy in modern medicine and society. AB - Autopsy rates continue to decline despite abundant evidence of the autopsy's value. Such an extraordinary contradiction requires that we look beyond issues of education to consider our basic moral and political commitments; to consider, in other words, the kind of society in which we live, and the kind of people we are. In a heterogeneous culture, we should not be surprised to find that even our most basic obligations may be in conflict. This essay draws on social and ethical perspectives to examine a peculiar phenomenon: the reluctance of physicians to have autopsies performed on themselves or their family members. Such behavior reflects an unintentional irony, a conflict between our societal commitments to treat dead persons properly and our professional commitments to remain self critical. The resources needed to resolve medicine's unintentional irony are to be found in our traditional language of medicine as a moral praxis, an uncertain but honorable craft devoted to the care of those who suffer. Autopsies remain the best way to learn whether or not clinical judgments are made correctly. Therefore, the autopsy is not an option; it is a professional obligation. We simply cannot hope to maintain our professional integrity as long as we proclaim the value of autopsies for our patients, but deny for ourselves and our families the same privilege. PMID- 2307441 TI - The changing role of the autopsy: a social environmental perspective. AB - Over the past decade, the declining autopsy rate has been the subject of much debate. Many articles in professional journals have explored both the cause of the decline as well as its desirability. Explanations for the declining rate of autopsies have typically been of two types, specifically "professional" and "technical." The former implicate declining professional standards, while the latter point to the emergence of new diagnostic technologies as the cause of the lower autopsy rate. This paper argues that both of these explanations are better understood as two components of a larger explanation known as the "social environmental perspective." Applied to the autopsy debate, the environmental perspective focuses on social, political, and economic forces that influence research hospitals and the different groups of people practicing within them. By placing the debate in a larger social framework, a more complete understanding of the declining autopsy rate may be reached. More important, it is hoped that the illumination of social processes affecting the work of medical professionals will encourage explicit discussions of those forces and possible ways of dealing with them. PMID- 2307442 TI - Perceptions of the autopsy: views from the lay public and program proposals. AB - The autopsy has historically served as a critical research and teaching tool in medicine as well as a means to ensure control over the quality of health care. In recent years, however, the autopsy has lost favor among the public and fallen into disuse within the medical community. This paper offers some insights into the reasons behind the decline of the autopsy as viewed by the lay public. Programs to help revitalize use of the autopsy are suggested. PMID- 2307443 TI - Toward a population-based assessment of death due to pulmonary embolism in New Mexico. AB - During a 5-year period (1981 through 1985), 586 of 46,512 (1.26%) deaths in New Mexico had pulmonary embolism (PE) listed on the death certificate. The frequency of death due to PE was mentioned more frequently in the autopsied than in the non autopsied component of the study (2.4% v 1.1%). This observation, together with published data on the accuracy of clinical diagnostics among persons dying with autopsy-documented PE, suggests that the frequency of death due to this disease is considerably higher than previously thought. Among autopsied persons who died of PE, risk factors and associated diseases are not appreciably different for those who die in or out of the hospital. Important associations with respect to persons dying of PE include male gender, advanced age, serious medical or surgical disease, immobilization, and trauma. PMID- 2307444 TI - The autopsy and vital statistics. AB - Vital statistics in the United States are collected through a decentralized, cooperative system of various levels of government administrated by the National Center for Health Statistics. Although registration of all deaths is virtually complete and demographic items are accurate, the reliability of cause of death data is hampered by the current state of medical knowledge, the incompleteness of information available at the time of death, the way in which physicians complete death certificates, and the system of classification of underlying cause. The need for quality assurance in national cause of death statistics can be met in large part by connecting the autopsy to the mainstream of vital statistics. Through case by case individual linkage of death certificates and autopsies in designated demographic and/or geographic areas, a representative, continuously collected, population-based system of aggregated autopsy data would be created. Demographic and clinical selection bias should be checked and adjusted through traditional methods of epidemiologic standardization. Such a use of autopsy information could further pathology's goals of understanding disease and improving the public health. PMID- 2307445 TI - A model for the autopsy-based quality assessment of medical diagnostics. PMID- 2307446 TI - Detection of specific t(14;18) chromosomal translocations in fixed tissues. AB - The present study was undertaken to establish the incidence of t(14;18) (q32:q21) chromosomal translocations detectable by a polymerase chain reaction (PCR) assay on fixed lymphoma biopsies. DNA samples from 113 formalin-fixed, paraffin embedded tissue biopsies (non-Hodgkin's lymphomas, 96 cases; Hodgkin's disease, six cases; reactive, 11 cases) were amplified by the PCR. Of the 96 non-Hodgkin's lymphoma cases, 56 had a follicular pattern and 40 had a diffuse pattern. Polymerase chain reaction-amplifiable t(14;18) chromosomal translocations were detected in 23 of 43 follicular low-grade lymphomas, one of eight follicular intermediate grade lymphomas, one of five follicular high-grade lymphomas, and one of 10 diffuse large-cell lymphomas. The remaining 30 diffuse lymphomas represented the spectrum of the Working Formulation classification. There were six biopsy specimens of Hodgkin's disease and 11 biopsy specimens of follicular hyperplasia; all were negative. The translocation was not detected in 16 biopsies (non-Hodgkin's lymphomas, seven cases; follicular hyperplasia, nine cases) from patients infected with the human immunodeficiency virus. Since this procedure uses the widely available fixed paraffin-embedded material, correlative studies between histology and genetic aberrations can be readily undertaken. PMID- 2307448 TI - Interactive morphometry of normal and hyperplastic peritoneal mesothelial cells and dysplastic and malignant ovarian cells. AB - This study used computerized interactive morphometry to evaluate the differential characteristics of mesothelial normal cells, mesothelial hyperplastic cells, and carcinomatous cells, and also compared hyperplastic mesothelial cells with ovarian dysplastic cells from a previous study. The procedure included extraction of multiple descriptors of the nuclear profile: perimeter length, area, longest chord, circularity factors, standard deviations of these characteristics, and a 10-bin size distribution table of the nuclear area. The final classification is achieved by stepwise discriminant analysis of these variables. The analysis classified all cases correctly with high posterior probabilities. PMID- 2307447 TI - Cytoskeletal properties of alveolar soft part sarcoma. AB - The immunohistochemical expression of cytoskeletal proteins in alveolar soft part sarcoma (ASPS) was studied by light and electron microscopy. Of the five cases examined by the avidinbiotin-peroxidase complex method, variable numbers of immunoreactive cells for desmin were found in three, for vimentin in two, for muscle-specific actins in three, and for alpha-smooth muscle actin in four. Immunoelectron microscopic study demonstrated that desmin and vimentin were localized on whorled bundles of intermediate filaments in the perinuclear cytoplasm. In addition, a few dispersed intermediate filaments became evident in specimens treated with saponin and fixed with tannic acid. These immunohistochemical results indicate that a few tumor cells of ASPS may express some properties of the cytoskeleton of smooth muscle cells in addition to those of skeletal muscle cells. Considering the discrepancies reported in the actin isoforms demonstrated in myogenic tumors, we conclude that ASPS is probably a peculiar, primitive myogenic tumor that does not show any distinctive features of rhabdomyogenic or leiomyogenic differentiation. PMID- 2307449 TI - Mitotically active leiomyomas of the uterus. AB - Seventy-three smooth-muscle tumors of the uterus, with five to nine mitotic figures per 10 high-power fields but lacking cytologic atypia, were studied. Pathologic features assessed included necrosis, hemorrhage, vascular intrusion, abnormal mitoses, and the number of mitotic figures. Vascular ingrowth by the tumor was present in 11 neoplasms. Follow-up ranged from 23 months to 15 years, with all patients alive and well at last contact. In 14 patients, myomectomy was the only treatment. Thirteen of these patients demonstrated no subsequent residual or recurrent tumor. One woman developed a persistent or recurrent mitotically active leiomyoma 8 years after myomectomy. We conclude that mitotically active smooth-muscle tumors of the uterus, having five to nine mitoses per 10 high-power fields and no cellular atypia, have a metastatic rate too low to be regarded as sarcomas. Hysterectomy need not automatically follow myomectomy if follow-up is done. PMID- 2307450 TI - Primary papillary hyperplasia of the gallbladder and cystic and common bile ducts. AB - A unique case of primary papillary hyperplasia of the gallbladder and cystic and common bile ducts occurring in a young female without calculi, ulcerative colitis, or primary sclerosing cholangitis is reported. The papillary lesion involved the mucosa of the entire gallbladder and of the cystic and common bile ducts. Histologically, the gallbladder mucosal folds were close to one another and taller than normal. They were lined by normal-appearing columnar cells and pencil-like cells. The papillary projections of the common bile duct were lined only by columnar cells with prominent subnuclear vacuoles. No endocrine cells or cytologic atypia were noted. The differential diagnoses, including secondary hyperplasia, multiple adenomas, and papillomatosis of the gallbladder, are discussed. PMID- 2307451 TI - Class II major histocompatibility antigen expression on coronary arterial endothelium in a patient with Kawasaki disease. AB - To investigate the class II major histocompatibility antigen expression on coronary arterial endothelium of Kawasaki disease and immunophenotypes of the infiltrating cells in the coronary vascular lesions, myocardial sections from a patient who died during the acute stage of Kawasaki disease were studied using an immunoperoxidase technique. The mononuclear cells in the lesions mainly consisted of macrophages and T cells, whereas B cells and NK/K cells were not seen. The majority of T cells reacted with Leu-3a antibodies, and only a few reacted with Leu-2a antibodies. Cells bearing the interleukin-2 receptor, indicative of activated T cells, were also found in the lesions. To determine the distribution of class II antigen, we used anti-HLA-DR antibodies. The massive expression of HLA-DR antigen on mononuclear cells was found in the lesions. In addition, the HLA-DR activation antigen was expressed on the coronary arterial endothelium at the infiltrates in which macrophages and T cells coexisted. In contrast, coronary arterial endothelium did not express HLA-DR antigens in the myocardial tissues of controls (n = 4). HLA-DR+ endothelial cells may play an important role in the development of Kawasaki vasculitis. PMID- 2307452 TI - Parathyromatosis in hyperparathyroidism. AB - Recurrent hyperparathyroidism after parathyroidectomy may present a difficult diagnostic problem. A rare etiology is parathyromatosis (multiple nodules of hyperfunctioning parathyroid tissue scattered through the neck and mediastinum) due to spillage of otherwise benign parathyroid tissue during surgery. We present a case of recurrent hyperparathyroidism and parathyromatosis due to tissue spillage during surgical removal of probable double adenomas, a rare cause of primary hyperparathyroidism. Thus, parathyromatosis must be included in the differential diagnosis of recurrent or persistent hyperparathyroidism, distinguished from parathyroid carcinoma by histologic criteria. The surgeon must be careful of parathyroid spillage during surgery, even of benign tumors of the parathyroids. PMID- 2307453 TI - Adenocarcinoid (goblet cell carcinoid) of the duodenum presenting as gastric outlet obstruction. PMID- 2307454 TI - A new glucose-6-phosphate dehydrogenase variant with congenital nonspherocytic hemolytic anemia (G6PD Genova). Biochemical characterization and mosaicism expression in the heterozygote. AB - A new deficient variant of glucose-6-phosphate dehydrogenase (G6PD) causing severe congenital nonspherocytic hemolytic anemia (CNSHA) is described. The variant enzyme, characterized by slow electrophoretic mobility, extreme in vivo and in vitro lability, high Km for G6P and strongly acidic pH optimum, appears to be unique, and has been designated G6PD Genova. Investigation of an obligate heterozygote using various cytochemical, biochemical and recombinant-DNA techniques showed G6PD mosaicism in the erythrocytes and leukocytes. Therefore, the presence of a disadvantageous mutation at one Gd locus did not determine selection in favor of the normal allele in the heterozygote's hemopoietic cells. PMID- 2307455 TI - Frequency and effect of human apolipoprotein A-IV polymorphism on lipid and lipoprotein levels in an Icelandic population. AB - Human apolipoprotein A-IV (apo A-IV) exhibits a genetic polymorphism with two common alleles, A-IV1 and A-IV2, in Caucasian populations. We have investigated this polymorphism in the Icelandic population. The frequencies of the two alleles are significantly different from middel European populations with a higher frequency of the A-IV2 allele (0.117 versus 0.077) occurring in Iceland. The alleles at the apo A-IV locus have significant effects on plasma high density lipoprotein cholesterol (HDL-C) and triglyceride levels. The average effect of the A-IV2 allele is to raise HDL-C by 4.9 mg/dl and to lower triglyceride levels by 19.4 mg/dl. We estimate that the genetic variability at the apo A-IV gene locus accounts for 3.1% of the total variability of HDL-C and for 2.8% of the total variability of triglycerides in the population from Iceland. This confirms and extends our previous observations on apo A-IV allele effects in Tyroleans in an independent population. PMID- 2307456 TI - Unusual X chromosome inactivation in a mentally retarded girl with an interstitial deletion Xq27: implications for the fragile X syndrome. AB - A de novo interstitial deletion (X)(q27.1q27.3), between the loci DXS 105 and F8, has been found in a mentally retarded female. The deleted X chromosome is preferentially early replicating in fibroblasts, B cells and T cells, suggesting that the missing region plays a role in inactivation of the X chromosome. None of the available DNA probes except DXS 98 maps to the deleted region of about 10,000 kb. The locus FRAXA is either included in the deletion, or located close to the distal break point. PMID- 2307457 TI - Lymphocyte and sperm chromosome studies in cancer-treated men. AB - To evaluate the reliability of the quantitative extrapolation of the long-term effect of cancer therapies from somatic cells to germ cells, we compared the frequency of chromosome abnormalities in 303 lymphocytes from four individuals treated with radio- and/or chemotherapy 5-18 years earlier with the frequency in 422 spermatozoa from the same individuals. The mean frequency of structurally abnormal complements was much higher in germ cells than in somatic cells (P = 2.08 x 10(-6)). The fact that spermatogenic cells share cytoplasm is suggested as a possible factor in the increased viability of germ cells with chromosome aberrations. In addition, in spermatozoa the incidence of structural chromosome abnormalities was much higher in treated individuals than in controls (P less than 0.00060), while in lymphocytes no statistically significant differences could be observed. This observation and the apparent lack of relationship between individual frequencies in the two kinds of cells suggest that the long-term effect of anti-tumor treatments on germ cells cannot be extrapolated from the analysis of somatic cells. PMID- 2307458 TI - A possible common origin of "Y-negative" human XX males and XX true hermaphrodites. AB - We have studied nine patients aged 1 month to 16 years with 46, XX karyotypes and testicular tissue. Some of these patients were followed through puberty. Phenotypically, two presented normal and seven abnormal external genitalia (AG). Among this latter group, four showed hypospadias and three true hermaphroditism (TH). The endocrine data were similar in all three groups: testosterone levels were within normal limits during puberty, decreasing in adulthood; gonadotrophin levels were above the control values at mid puberty. Histologies of the two sub groups of AG patients were identical up to 5 years of age and presented differences when compared with controls, regardless of the ovarian part of the ovotestis. However, in patients older than 8 years, germ cells disappeared and dysgenesis became obvious. In one patient, the ovarian zone of the gonad was detected only after complete serial sections of the removed gonad were examined. Southern blot analysis with Y-DNA probes displayed Y-specific material for the classic 46 XX males and a lack of such sequences for all patients with AG and TH. Based on these findings, we postulate that 46, XX males with AG and 46, XX TH may represent alternative manifestations of the same genetic defect. These data together with those concerning familial cases of 46, XX males with AG and 46, XX TH suggest an autosomally (or pseudoautosomally) determined mechanism. PMID- 2307459 TI - Mitotic disturbance associated with mosaic aneuploidies. AB - The association of various unsystematic aneuploidies with premature centromere division (PCD) was observed in a patient with conspicuous clinical features and combined immunodeficiency. Trisomies and monosomies of almost all autosomes and gonosomal aberrations were found separately or in combination in a majority of the proband's lymphocytes and fibroblasts. The chromosome number varied from 44 to 50. A high proportion of the metaphases showed PCD or had the appearance of C anaphases. These findings probably represent a new mutant affecting mitosis and causing mosaic aneuploidies. PMID- 2307460 TI - Hb D Los Angeles (D-Punjab) and Hb Presbyterian: analysis of the defect at the DNA level. AB - Amplification of the beta-globin gene by the polymerase chain reaction (PCR) and direct sequencing were used for a fast and reliable identification of the beta globin variant Hb D Los Angeles and revealed the predicted G----C substitution in codon 121. The same method showed the molecular defect in Hb Presbyterian to be a C----G substitution in codon 108; this eliminates a MaeII restriction site. PMID- 2307461 TI - Replication studies in the 16p+ variant. AB - We report a further case of the 16p+ chromosome studied by replication banding. The extra euchromatic material was shown to be uniformly light staining, indicating that it is late replicating. PMID- 2307462 TI - An insertion deletion polymorphism in the signal peptide of the human apolipoprotein B gene. AB - In this communication we report the genetic properties of an insertion/deletion polymorphism in the signal peptide of the human apolipoprotein B (apo b) gene. There are two alleles of the apo B signal peptide; one codes for a peptide 27 amino acids in length and the other a peptide only 24 amino acids in length. Using the polymerase chain reaction the difference of nine nucleotides between the two alleles is readily detectable after electrophoresis of the amplification products. The relative frequencies of the Ins and Del alleles are 0.655 and 0.345, respectively. The apo B signal peptide genotypes are transmitted in a manner consistent with an autosomal codominant mode of inheritance with two alleles. PMID- 2307463 TI - Definition of an acquired 11q deletion in a tumorigenic human monocytic cell line. PMID- 2307465 TI - Organization of DYZ2 repetitive DNA on the human Y chromosome. AB - The location of the human Y-specific repetitive DNA sequence DYZ2 with HaeIII cleavage sites spaced at 2.1 kb was reexamined. Previous reports had mapped the 2000 DYZ2 copies to the very distal end of the heterochromatic Yq12 band. In the present study, a cloned DYZ2 fragment (pHY2.1) was used for Southern and slot blot analyses of male DNA as well as for nonradioactive in situ hybridization to chromosomes. DNA and metaphase preparations from 79 individuals with polymorphic or aberrant Y chromosomes were examined. DYZ2 repeats are not confined to the distal tip of Yq12, but extend through the entire heterochromatin of Yq12. In the naturally occurring length polymorphisms of Yq, the amount of DYZ2 sequence varies in proportion to the measured sizes of band Yq12. Explanations are presented for the fact that previous studies restricted the location of DYZ2 to the telomeric end of Yq12. PMID- 2307464 TI - Identification of two human ferritin H genes on the short arm of chromosome 6. AB - We have found by analyses of human-hamster hybrid cells that two human ferritin H genes lie near the locus of the iron storage disease idiopathic hemochromatosis on chromosome 6p. One of these genes was isolated and shown to be a processed pseudogene. Comparison of its sequence with those of other ferritin H pseudogenes indicates that they may be derived from a functional H gene other than that on chromosome 11. PMID- 2307466 TI - Molecular analysis of deletions in the human beta-globin gene cluster: deletion junctions and locations of breakpoints. AB - DNA fragments that contain the deletion junction regions of four independent deletions involving the human beta-globin gene cluster have been isolated and cloned. The fragments were isolated from individuals with the conditions referred to as Sicilian (delta beta)zero-thalassemia, Turkish G gamma+(A gamma delta beta)zero-thalassemia, Black G gamma+(A gamma delta beta)zero-thalassemia, and HPFH-2. The sequences of the deletion junctions and of the normal DNA surrounding their 3' breakpoints were determined and compared to the previously determined sequences of normal DNA surrounding their 5' breakpoints. These comparisons show that the deletions were the result of nonhomologous recombinational events. Two of the deletion junctions contain "orphan" nucleotides, while the other two show very limited amounts of "junctional homology." Both types of junctions are common among recombination events in mammalian cells and we discuss a simple joining scheme that could account for the junctions reported here. Unlike other deletions in this cluster and in other gene clusters, none of the eight deletion breakpoints examined here occurred within Alu family repeats. To examine the significance of deletion breakpoints within various sequence categories, we analyzed the data from a well-defined set of deletions within this locus. In contrast to deletions in the alpha-globin gene cluster, the occurrence of breakpoints in Alu family repetitive sequences is not statistically significant within the beta-globin gene cluster. However, breakpoints do occur within transcriptional units of the beta-globin gene cluster more frequently than expected by chance alone. We conclude from our analysis that the mechanisms of DNA joining are not locus or location specific, but at least a portion of the mechanisms of chromosomal breakages do show locus specificity. PMID- 2307467 TI - Identification of a closely linked DNA marker, DXS178, to further refine the X linked agammaglobulinemia locus. AB - X-linked agammaglobulinemia (XLA) is an inherited recessive disorder in which the primary defect is not known and the gene product has yet to be identified. Utilizing genetic linkage analysis, we previously localized the XLA gene to the map region of Xq21.3-Xq22 with DNA markers DXS3 and DXS17. In this study, further mapping was performed with two additional DNA probes, DXS94 and DXS178, by means of multipoint analysis of 20 families in which XLA is segregating. Thirteen of these families had been previously analyzed with DXS3 and DXS17. Three crossovers were detected with DXS94 and no recombinations were found between DXS178 and the XLA locus in 9 informative families. Our results show that XLA is closely linked to DXS178 with a two-point lod score of 4.82 and a multipoint lod score of 10.24. Thus, the most likely gene order is DXS3-(XLA,DXS178)-DXS94-DXS17, with the confidence interval for location of XLA lying entirely between DXS3 and DXS94. In 2 of these families, we identified recombinants with DXS17, a locus with which recombination had not previously been detected by others in as many as 40 meiotic events. Furthermore, DXS178 is informative in both of these families and does not show recombination with the disease locus. Therefore, our results indicate that DXS178 is linked tightly to the XLA gene. PMID- 2307468 TI - A complex of serine protease genes expressed preferentially in cytotoxic T lymphocytes is closely linked to the T-cell receptor alpha- and delta-chain genes on mouse chromosome 14. AB - A complex of genes encoding serine proteases that are preferentially expressed in cytotoxic T-cells was shown to be closely linked to the T-cell receptor alpha- and delta-chain genes on mouse chromosome 14. A striking difference in recombination frequencies among linkage crosses was reported. Two genes, Np-1 and Tcra, which fail to recombine in crosses involving conventional strains of mice, were shown to recombine readily in interspecific crosses involving Mus spretus. This difference in recombination frequency suggests chromosomal rearrangements that suppress recombination in conventional crosses, recombination hot spots in interspecific crosses, or selection against recombinant haplotypes during development of recombinant inbred strains. Finally, a mutation called disorganization, which is located near the serine protease complex, is of considerable interest because it causes an extraordinarily wide variety of congenital defects. Because of the involvement of serine protease loci in several homeotic mutations in Drosophila, disorganization must be considered a candidate for a mutation in a serine protease-encoding gene. PMID- 2307469 TI - A physical map of the human salivary proline-rich protein gene cluster covers over 700 kbp of DNA. AB - By using a linking library, we have experimentally linked, ordered, and spaced four of the six loci that constitute the human salivary proline-rich protein (PRP) multigene family. The methods used for mapping these four PRP genes may be useful in other multigene systems in which no probes unique to each member of genes are available, but in which some enzyme site that occurs only once in each member of the family can be found. The remaining two PRP loci have been provisionally mapped and linked within the gene cluster primarily on the basis of the resulting order giving a simple map. The order of the six loci that most simply accounts for our data is PRB2, PRB1, PRB4, PRH2, PRB3, and PRH1. The PRP gene cluster spans at least 700 kbp on chromosome 12 at p13.2. A scheme for the evolution of the cluster that requires an initial gene duplication followed by three unequal but homologous crossovers is given. PMID- 2307470 TI - Isolation and chromosomal localization of the human glutathione peroxidase gene. AB - We have isolated cDNA clones for the gene, termed GPX1, encoding the major human selenoprotein, glutathione peroxidase. Sequence analysis confirmed previous findings that the unusual amino acid seleno-cysteine is encoded by the opal terminator codon UGA. Southern blot analysis of human genomic DNA with the GPX1 cDNA showed that restriction endonucleases without sites in the probe sequence produced three hybridizing bands at standard stringency, diminishing to one strongly and one weakly hybridizing band at high stringency. In situ hybridization localized the human GPX1 gene to a single site on chromosome 3, at region 3q11-13.1. Thus, three genomic sites bear sequence homology to the GPX1 cDNA, and the one most homologous maps to 3q11-13.1. PMID- 2307471 TI - A physical map around the retinoblastoma gene. AB - The gene predisposing to retinoblastoma, RB1, has been mapped to 13q14 and a cDNA clone has been isolated. Alterations of this chromosomal region are found not only in retinoblastoma, but in other tumor types including bone and soft tissue sarcomas, gastric tumors, small cell lung cancer, hematologic malignancies, rhabdomyosarcoma, and breast cancer. Genetic alterations implicating RB1 in some of these cancers have been observed. A long-range, overlapping restriction map around RB1 has been derived to provide a basis for study of rearrangements in tumors. Putative CpG islands closely linked to RB1 were identified, the effect of methylation was investigated, and RB1 transcriptional direction was determined. Using data in the literature, the map was oriented with respect to the centromere and it was determined that the distance between esterase D, a nearby gene, and RB1 was greater than 200 kb. PMID- 2307472 TI - Mapping of the two mouse engrailed-like genes: close linkage of En-1 to dominant hemimelia (Dh) on chromosome 1 and of En-2 to hemimelic extra-toes (Hx) on chromosome 5. AB - The mouse genome contains two genes, En-1 and En-2, with sequence similarity to the engrailed gene of Drosophila. Using conventional linkage crosses, we have shown that En-1 maps approximately 0.28 cM distal to the dominant hemimelia (Dh) gene on chromosome 1 and that En-2 maps approximately 1.1 cM proximal to the hemimelic extra-toes (Hx) gene on chromosome 5. We have also shown by Northern blot analysis that En-1 transcripts in Dh homozygotes and En-2 transcripts in Hx homozygotes are of normal size and abundance. These data, in conjunction with previously published studies of the patterns of En-1 and En-2 expression in developing mouse embryos, suggest that Dh and Hx are very unlikely to be mutant alleles of En-1 or En-2, respectively. Instead, we suggest that En-1-Dh and En-2 Hx represent paralogous linkage groups that evolved following duplication of a common ancestral chromosome segment. PMID- 2307473 TI - A primary linkage map of the human chromosome 11q22-23 region. AB - We have constructed a genetic map of the human chromosomal region 11q22-23 by multipoint linkage analysis of 13 DNA polymorphisms that we have condensed into eight loci. An analysis for linkage disequilibrium between tightly linked probe/enzyme systems allows us to make specific recommendations for future DNA typing at these loci. The resulting sex-averaged multipoint map spans approximately 80 cM and differs considerably from previously reported genetic maps of this region. Our mathematically derived "most likely order" of the markers is compatible with physical mapping data using somatic cell hybrids. The known localizations of at least 14 functional genes and several disease loci to 11q22-23, including ataxia telangiectasia, make the mapping of this region especially relevant to studies of disease pathogenesis. PMID- 2307474 TI - The syntenic relationship of proximal mouse chromosome 7 and the myotonic dystrophy gene region on human chromosome 19q. AB - The syntenic relationship of the myotonic dystrophy (DM) gene region on human chromosome 19q and proximal mouse chromosome 7 was examined using an interspecific backcross between C3H/HeJ-gld/gld mice and Mus spretus. Segregation analyses were used to order homologs of nine human loci linked with the DM gene. Their order from the centromere was Prkcg, [Apoe, Atpa-2, Ckmm, D19S19h, Ercc-2], Cyp2b, Mag, Lhb. Two other murine loci, D7Rp2 and Ngfg, were also positioned within this interval. Homologs for five human chromosome 11 and 15 loci (Calc, Fes, Hras-1, Igflr, Tyr) were localized within an 18-cM span telomeric to Lhb. Comparison of the gene orders indicates an inversion extending from Prkcg through the interval between Mag and Lhb. This study establishes a detailed map of proximal mouse chromosome 7 that will be useful in identifying and determining whether new human chromosome 19 probes are linked to the DM region. PMID- 2307475 TI - A molecular genetic linkage map of mouse chromosome 13 anchored by the beige (bg) and satin (sa) loci. AB - A molecular genetic linkage map of mouse chromosome 13 was constructed using cloned DNA markers and interspecific backcross mice from two independent crosses. The map locations of Ctla-3, Dhfr, Fim-1, 4/12, Hexb, Hilda, Inhba, Lamb-1.13, Ral, Rrm2-ps3, and Tcrg were determined with respect to the beige (bg) and satin (sa) loci. The map locations of these genes confirm and extend regions of homology between mouse chromosome 13 and human chromosomes 5 and 7, and identify a region of homology between mouse chromosome 13 and human chromosome 6. The molecular genetic linkage map of chromosome 13 provides a framework for establishing linkage relationships between cloned DNA markers and known mouse mutations and for identifying homologous genes in mice and humans that may be involved in disease processes. PMID- 2307476 TI - Monochromosomal rodent-human hybrids from microcell fusion of human lymphoblastoid cells containing an inserted dominant selectable marker. AB - An improved system for the production of a series of rodent-human hybrids selectively retaining single human chromosomes marked in known locations is described. Such hybrids have significant applications in gene mapping and other genetic studies. Human lymphoblastoid lines were infected with the retroviral vector SP-1, which contains the bacterial his-D gene allowing mammalian cells to grow in the presence of histidinol. Microcell fusion of the infected lymphoblastoid cells with CHO cells was used to produce hybrids containing single human chromosomes retained by histidinol selection. Hybrids containing a single human chromosome 9 and a single human chromosome 19 are described. These have been characterized cytogenetically by G-banding, in situ hybridization, and Southern blot analysis. PMID- 2307477 TI - Localization of the choline acetyltransferase (CHAT) gene to human chromosome 10. AB - A cDNA clone encoding the complete sequence of porcine choline acetyltransferase (CHAT) isolated by S. Berrard et al. (1987, Proc. Natl. Acad. Sci. USA 84: 9280 9284) was hybridized to TaqI digests of a panel of 25 human-rodent somatic cell hybrids and to a complementary panel of 10 human-rodent hybrids in order to determine the chromosomal localization of human CHAT. To enhance the detection of the human signal, hybridization and washings were performed under low stringency conditions on membranes presaturated with sonicated DNA from parental rodent strains. All informative human fragments had the same distribution among the hybrids, mapping CHAT to a single human chromosome. CHAT was assigned to chromosome 10 because all other chromosomes were eliminated by exclusion based on the analysis of the signal segregation. This result indicates that mutation of the CHAT gene cannot be responsible for the primary defect in familial Alzheimer's disease. PMID- 2307478 TI - The gene for the microsomal glutathione S-transferase is on human chromosome 12. AB - The microsomal glutathione S-transferase (GST) is a unique membrane-bound GST structurally distinct from the cytosolic GSTs. A cDNA encoding this 154 amino acid protein has recently been isolated and characterized. Using the cDNA as the hybridization probe, we now report the assignment of the human microsomal GST gene to chromosome 12 through the use of a panel of mouse-human somatic cell hybrid lines. This locus has recently been designated as GST 12. In addition, genomic Southern blotting data suggest that the human microsomal GST is encoded by a single- or very-low-copy gene. Therefore, the human GST gene superfamily resides on at least four separate chromosomes: 1 (GST 1), 6 (GST 2), 11 (GST 3), and 12 (GST 12). PMID- 2307479 TI - Chromosomal localization of the gene encoding GTPase-activating protein (RASA) to human chromosome 5, bands q13-q15. PMID- 2307480 TI - The serum polymeric IgA antibody response to typhoid vaccination; its relationship to the intestinal IgA response. AB - The relationship between the IgA antibody response in serum (total and polymeric IgA) and intestinal secretions was examined in volunteers subjected to oral and parenteral typhoid vaccination. After oral vaccination (three doses of 10(11) live Ty21a vaccine given at 48-hr intervals), serum pIgA antibody to typhoid lipopolysaccharide (LPS) was detected in seven of the 14 subjects (46.4 +/- 59 U/100 microliters, mean +/- SD). However, all 14 showed a significant intestinal IgA response (993 +/- 2516 and 9349 +/- 6754 U/mg pre- and post-vaccine; t = 5.25, P = 0.0002). The level of pIgA antibody declined rapidly, whereas intestinal IgA antibody levels remained elevated. Serum pIgA antibody was also found after parenteral immunization (two doses of 5 X 10(8) heat-killed bacteria given 14 days apart to six subjects), but an intestinal IgA antibody response was detected in these individuals only after a subsequent course of the oral vaccine given 1 month after initial parenteral immunization. Changes in serum pIgA antibody followed those of total serum IgA antibody rather than those of intestinal antibody. The results indicate that a serum pIgA response can be induced by an antigenic stimulus delivered either orally or parenterally, whereas an intestinal IgA response is induced only by a local antigen stimulus. The regulation of serum pIgA and intestinal IgA appear to be independent. PMID- 2307482 TI - The genetic regulation of the induction of experimental SLE. AB - We have recently reported the induction of systemic lupus erythematosus (SLE) in C3H.SW female mice by their immunization with a human monoclonal anti-DNA antibody that bears a common idiotype termed 16/6 Id. In the present study, the ability to induce experimental SLE in seven inbred mouse strains by immunization with the 16/6 Id was examined. Two out of the seven strains failed to develop the disease. These two strains did not produce antibodies specific to the 16/6 Id, while the other five strains produced high titres of anti-16/6 Id antibodies. The anti-16/6 Id antibody response, followed by the induction of the disease, was not found to be MHC or Ig heavy chain allotype linked. F1 hybrids between a resistant strain and two of the susceptible strains were found to be resistant to the induction of the disease, indicating that susceptibility is inherited as a recessive trait. In the autoimmune NZB/W F1 female mice, immunization with the 16/6 Id resulted in an early onset of the SLE-like disease. The results of the present study indicate the role of the anti-16/6 Id antibodies in the induction of experimental SLE, and provide direct evidence for the importance of the genetic background in determining susceptibility to SLE. PMID- 2307481 TI - Interleukin-2-dependent control of disease development in spontaneously diabetic BB rats. AB - Long-term treatment with recombinant interleukin-2 (IL-2) of diabetes-prone BB rats had contrasting effects in two different BB rat sublines. Diabetes development was enhanced in the subline with a low intrinsic diabetes risk and suppressed in the subline with a high diabetes risk. IL-2 treatment started between 35 and 42 days of age and lasted for 3 months. In subline 1, diabetes incidence increased from 23% to 53% (P less than 0.01), in subline 2 it decreased from 73% to 32% (P less than 0.01). The two sublines differed in serum levels of factors controlling IL-2 synthesis and activity. Mean IL-2 inhibitory activity was higher in subline 2 (between 140% and 290% of levels in subline 1, P less than 0.01). Conversely, mean concentrations of thymosin alpha 1 and beta 4 were higher in subline 1 (between 140% and 200% of levels in subline 2, P less than 0.01). Thus the two sublines differ in their response to exogenous IL-2 and also in serum levels of mediators affecting availability of IL-2. We conclude that an internal network of hormonal factors, including IL-2, contributes to the control of diabetes development in the BB rat. PMID- 2307483 TI - The effect of human placental protein 14 (PP14) on the production of interleukin 1 from mitogenically stimulated mononuclear cell cultures. AB - Crude human decidual tissue extracts containing placental protein 14 (PP14) were shown to inhibit the production of interleukin-1 beta (IL-1) from mitogenically stimulated mononuclear cell cultures. The inhibition was dose-dependent over the range of PP14 concentrations investigated (0-8.0 mg/l) and was effective on both phytohaemagglutinin-(PHA) and lipopolysaccharide- (LPS)-induced IL-1 secretion. Using these culture systems, a PP14 concentration of 1.0 mg/l induced a 34% suppression of IL-1 secretion following LPS stimulation and 22% following PHA stimulation. For PHA stimulation the suppression of IL-1 secretion was effective throughout the culture period investigated (0-89 hr). Individual crude decidual extracts inhibited the incorporation of [3H]thymidine into PHA-stimulated lymphocytes, such inhibition being partially reversed by the addition of exogenous recombinant IL-1 to the cultures. These results suggest that the previously reported immunosuppressive activity of PP14 may be mediated by the suppression of IL-1 secretion. PMID- 2307484 TI - Three B-cell surface molecules associating with membrane immunoglobulin. AB - Three cell-surface molecules associated with surface Ig on murine B cells have been identified. Surface-iodinated resting B cells were lysed in digitonin or Nonidet P-40. The lysates were then examined by immunocoprecipitation with anti Ig reagents and SDS-PAGE. By this procedure, a 73,000 MW heterodimer, composed of 35,000 and 38,000 MW disulphide-linked subunits, was found to be associated with both mIgM and mIgD. This association was detectable in the detergent digitonin, but not Nonidet P-40. As an alternative approach, resting B cell mIg was capped and internalized by anti-Ig induced mIg cross-linking. The resulting 'modulated' cells were then screened for surface reactivity with a panel of monoclonal antibodies. Most antibodies tested (anti-class I, -class II, -LFA, -FcR gamma, FcR epsilon) reacted equally well with control and modulated B cells. With two, however, there was a significant reduction in surface representation on modulated B cells. One determinant corresponds to a previously undescribed 90,000 MW murine surface marker, and the other was a polydisperse glycoprotein recognized by the mAb J11D. PMID- 2307485 TI - Growth of murine thymocytes in vitro in chemically defined medium. AB - Immature T cells proliferate, diversify their repertoire of antigen specificity, are selected for MHC-restricted function, are selected for non-self reactivity and undergo maturation in the thymus. The mechanisms underlying thymic development are poorly understood. One reason for this is that murine thymocytes generally die when cultured in vitro under conditions which normally support lymphocyte growth. We describe conditions under which CD4-CD8- thymocytes proliferate at a high rate and acquire maturation-associated markers in vitro in the absence of exogenous mitogenic stimuli. CD4+CD8- cells also multiplied in the absence of added lymphokines while CD4-CD8+, but not CD4+CD8+, cells proliferated in the presence of exogenous IL-2. Proliferation of CD4-CD8- cells was associated with production of both IL-1 and IL-2. Proliferation of unfractionated, CD4-CD8- and CD4+CD8- thymocytes was dependent upon interaction of IL-2 with its receptor. CD4-CD8- cells acquired CD4 and/or CD8 markers during culture, indicating that, in addition to the proliferation, some maturation occurred. Proliferation occurred in complexes containing one or more central stromal cells. The results are discussed in relation to their possible relevance to thymocyte development. PMID- 2307486 TI - Human rTNF alpha augments anti-bacterial resistance in mice: potentiation of its effects by recombinant human rIL-1 alpha. AB - Treatment with human recombinant tumour necrosis factor-alpha (rTNF alpha) significantly enhanced resistance to Listeria monocytogenes infection in mice. The level of protection (which was dose-dependent and maximal at approximately 1.0 microgram per mouse) was similar to that previously reported for the monokine rIL-1 alpha, although somewhat greater amounts of rTNF alpha than rIL-1 alpha were required. Combined administration of suboptimal concentrations of rTNF alpha and rIL-1 alpha resulted in significant enhancement of resistance beyond that obtained with either monokine alone, whereas further increases in anti-listeria resistance were not observed at doses of rTNF alpha or IL-1 alpha that were themselves capable of inducing substantial protection. Combined administration of rTNF alpha and rIL-1 alpha was associated with a delay in onset and lessening in severity of the lymphopenia that accompanied L. monocytogenes infection. The reduced bacterial burden in the spleens and livers of mice treated with rTNF alpha and rIL-1 alpha was associated with a more rapid decline in serum colony stimulating activity. Peritoneal macrophages from rTNF alpha- and rIL-1 alpha treated listeria-infected mice did not demonstrate enhanced anti-listeria activity in vitro. These results provide further evidence for the potential benefits of rTNF alpha and other cytokines in promoting anti-bacterial resistance. They further suggest that use of combinations of cytokines is a strategy worthy of further consideration. PMID- 2307487 TI - Location of membrane-bound hapten with different length spacers. AB - Immunogenic activity of a lipid hapten is strongly dependent of the length and nature of the linker chain (spacer) connecting the hapten to the head group of the lipid. A derivative containing a very short or a long spacer is known to be less effective for antibody binding than that of an intermediate length. In the present experiment, this was confirmed first by experiments of antibody binding to TNP lipid haptens with different length of spacers and of antibody-dependent macrophage binding to them. Second, we determined the location of the TNP haptens in lipid bilayer membranes by fluorescence energy transfer. It was found that vertical distances between TNP groups (acceptors), which were assumed to be randomly distributed in a plan parallel to the membrane surface, and a pyrene fluorophore (donor), which was embedded in the middle of lipid membranes, were 10.2-10.5 A in the DMPC membranes and 13.2-13.9 A in the DPPC membranes. The vertical distances were about 3 A longer in the DPPC membranes than in the DMPC membranes. However, they were almost independent of the length of spacers. This indicates that TNP residues of the lipid haptens locate at the similar vertical position on the membrane surfaces even if they have different length spacers. From these results we suggested that the affinity of the spacer groups to the bilayer surfaces can modulate the binding affinity of antibody to lipid hapten on the membrane surfaces. This was partly supported by the binding experiments of TNP spacers to the bilayer membranes. PMID- 2307488 TI - Enhanced production of interleukin 1 by mouse peritoneal macrophages after aclacinomycin administration. AB - The peritoneal cells of mice injected with aclacinomycin (ACM), an oncostatic drug of the anthracyclin family, were found to secrete more interleukin (IL-1), after two successive 24-h periods of in vitro LPS stimulation than those of control mice. This measured IL-1 production is one of the signs of enhanced macrophage activity. The cells of ACM-injected mice also contained more intracellular IL-1 than those of controls. In contrast, macrophages from ACM injected mice only increased their IL-1 production after the first 24-h incubation with PMA, and not after the second 24-h incubation. The response to ACM was dose- and time-dependent. We have also compared the IL-1 production by macrophages from mice injected with other anthracyclins, at doses equimolar to that of 4 mg/kg ACM and we have observed that adriamycin, 4'-epiadriamycin and aclacinomycin had similar activity, while THP-adriamycin an daunorubicine were slightly more active. Exploitation of this increased IL-1 production by macrophages could be beneficial in the design of tumor treatment protocols. PMID- 2307489 TI - Modifications of sialidase activity during the monocyte-macrophage differentiation in vitro. AB - Human mononuclear cells were isolated from peripheral blood by centrifugation over Ficoll Hypaque, followed by adherence to plastic dishes. Monocyte-derived macrophages were obtained after culture for 3 or 5 days of the adherent cells in RPMI medium containing 20% heat-inactivated foetal calf serum. The sialidase activities were assayed in the whole homogenate using sodium 4-methyl umbelliferyl-alpha-D-neuraminate as substrate, at various pHs, ranging from 3.6 to 6. The in vitro differentiation of monocytes into macrophages from day 0 up to day 5 was accompanied by a significant (P less than or equal to 0.01) increase in the sialidase activity on both a per-cell (+360%) and a per-mg protein in the homogenate (+125%) basis. PMID- 2307490 TI - Anti-phospholipid antibody isotypes in normal human sera. AB - Heat-sensitive serum masking cofactor(s) of antiphospholipid antibody (aPL) in normal human sera (NHS) are specifically inactivated at 56 degrees C. The degree of binding in ELISA by unmasked aPL in NHS was equivalent to that in non-heated, aPL-reactive autoimmune SLE sera. Previously "negative" SLE sera also reacted equally strongly in the aPL ELISA when similarly heat-inactivated. Isotype studies by ELISA of the heat-potentiated aPL in 36 NHS revealed the presence of specific IgG (34/36), IgM (11/36) and IgA (24/36) aPL antibodies. 11/36 (31%) NHS had all three aPL isotypes while 13/36 (36%) had both IgG and IgA antibodies to phospholipid. PMID- 2307491 TI - Interpretation of the cross-reactivity of anti-DNA antibodies with cell surface proteins: the role of cell surface histones. AB - The putative cross-reaction of anti-DNA antibodies with "lupus-associated membrane proteins (LAMP)" on the surface of intact Raji cells was examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analyses. Cell surface proteins of 14, 17, 18, 33 and 34 kDa were detected by monoclonal anti-double-stranded (ds) DNA antibodies and the sera of patients with systemic lupus erythematosus (SLE) in active states, but were not detected by the sera of SLE patients in inactive states, nor in healthy controls. However, pre-treatment of these anti-DNA antibodies with DNase I markedly reduced the reactivity to the cell surface proteins. Judging from the electrophoretic mobility, these proteins were identical with histones, and purified histones inhibited the reaction of anti-DNA antibodies with the cell surface proteins. Moreover, affinity-purified antihistone antibodies could demonstrate histones in the Raji cell surface proteins. Thus, we conclude that "cross-reaction" of anti DNA antibodies with LAMP is due to DNA-anti-DNA immune complexes which could react with cell surface histones. PMID- 2307492 TI - Immunological specificity of monoclonal antibodies to Chlamydia psittaci ovine abortion strain. AB - Fifty-one monoclonal antibodies were prepared by two different techniques against Chlamydia psittaci strain A22 isolated from an ovine abortion. These antibodies were tested for reactivity by the indirect immunofluorescent antibody technique with eleven reference Chlamydia strains (nine C. psittaci, one Chlamydia trachomatis and one Chlamydia pneumoniae). Four classes of specificity were recognized for monoclonal antibodies: genus, species, subspecies and type specificity. The type-specific monoclonal antibodies were non-reactive with ovine arthritis isolates. Twenty monoclonal antibodies were specific for two mammalian strains: ovine abortion A22 and K mouse. Some monoclonal antibodies were reactive with C. pneumoniae strains and non-reactive with C. trachomatis strains. All these monoclonal antibodies were very useful for improving the diagnosis of chlamydial infection, the antigenic analysis and the serotyping of C. psittaci. PMID- 2307493 TI - Mitogen-induced initiation of DNA synthesis by lymphocytes cultured in serum-free media. PMID- 2307494 TI - Fatal strongyloidiasis in India. PMID- 2307495 TI - Surgery in uncomplicated duodenal ulcer: are we close to the ideal operation? PMID- 2307496 TI - Anterior seromyotomy with posterior truncal vagotomy in chronic duodenal ulcer. AB - Anterior seromyotomy with posterior truncal vagotomy was carried out on 25 patients with chronic duodenal ulcer to evaluate its effectiveness as an acid reducing procedure. There was a 76.7% and 76.8% reduction in basal and maximal acid output respectively (augmented histamine test). Twenty-three patients were asymptomatic at 4-6 years' follow-up, while two patients had delayed gastric emptying not necessitating reoperation. There was no mortality. This procedure is a reasonable alternative to highly selective vagotomy. PMID- 2307497 TI - Ischemic bowel disease. AB - Twenty-five cases with ischemic bowel disease seen over a period of 4 years are presented. Of these, 20 cases presented with acute symptoms and five with chronic symptoms. In the majority of patients, the diagnosis was established at operation and on histopathology. Occlusive disease of the superior mesenteric artery was the commonest cause of acute ischemia. Non-occlusive ischemia was not observed in any case. All the patients were treated by resection and anastomosis of the involved bowel. Vascular procedures were not carried out in any. No planned second-look procedures were carried out. Of the 20 acute cases, eight patients died and three developed complications. One chronic case died and there were no other complications in this group. We suggest that ischemic bowel disease should be considered while dealing with cases presenting as acute abdomen or with chronic abdominal pain. PMID- 2307498 TI - Comparison of stool microscopy and serology (enzyme linked immunosorbent assay) in epidemiology of amebiasis. AB - Stools from 634 individuals from Varanasi were examined for Entamoeba histolytica (EH). Serology was done in these subjects by enzyme linked immunosorbent assay (ELISA) employing filter paper technique. Stools were positive for EH in 16.9%, and serology in 15.9%. Both the tests were positive in only 5.2%. In 72.4% both the tests were negative. In 11.7% of stool positive cases, serology was negative, and in 10.7% with positive serology stool examination did not reveal EH. A majority (92.5%) of stool positive subjects had only cysts. Additional parasites were detected in 15.3%. PMID- 2307499 TI - Neuroticism in patients with irritable bowel syndrome. AB - Employing a Hindi adaptation of the Middlesex Hospital Questionnaire (MHQ), neuroticism level was assessed in 133 subjects with irritable bowel syndrome and compared with that in patients with organic bowel disease (33), healthy population (140) and known neurotics (110). Compared with healthy controls and patients with organic bowel disease, significantly higher scores were found among irritable bowel syndrome patients in all the subscales except obsession. The total of scores was midway between those of the normal population and known neurotics. Neurotic disorder was detected in 51% of irritable bowel syndrome patients compared to 24% of organic bowel disease subjects (P less than 0.05) and 7.8% of the healthy population. Cut-off points, calculated as mean + 2 SD of scores in the healthy population, were found to be reliable as shown by clinical interview. PMID- 2307500 TI - Endoscopic polypectomies in upper gastrointestinal tract. AB - Nine polyps retrieved from the upper gastrointestinal tract by endoscopic polypectomy in nine patients are reported. Polyps were removed from the distal esophagus (1), stomach (7) and duodenum (1). Dysphagia, obstructive jaundice and upper gastrointestinal bleeding were the presenting features in four patients. In five patients gastric polyps were detected incidentally at endoscopy. Of the nine polyps, six were adenomas, two were hyperplastic polyps and one in the esophagus was inflammatory. All the polyps could be retrieved completely and there were no complications. Thus polyps do occur in the upper gastrointestinal tract in India; their electrosurgical removal is easy and safe and allows histopathological examination of the entire polyp. PMID- 2307501 TI - Effect of various doses of medroxyprogesterone acetate on intestinal functions in rats. AB - The dose relationship between medroxyprogesterone acetate (MPA), a long acting contraceptive, and rat intestinal digestive and absorptive functions has been investigated. The study revealed that the activities of brush border sucrase, lactase and leucine aminopeptidase were stimulated only at high doses, viz 70 mg/kg (180 mumol/kg) body weight and above, whereas the activity of alkaline phosphate was depressed at comparatively low dose (17.5 mg/kg; 45 mumol/kg body weight). This decrease was found to be significant (p less than 0.001) at all the doses tested. The inhibition in the intestinal uptake of calcium paralleled the decrease in alkaline phosphatase activity. Relatively high amount of MPA (140 mg/kg; 360 mumol/kg) was required to augment the uptake of glucose and amino acid. The results obtained do not indicate a close relationship between the dose of the drug and the extent of alteration in the rat intestinal digestive and absorptive functions. The study appears to confirm the association between brush border enzymes activities and uptake of nutrients in rat intestine. PMID- 2307502 TI - Hemostatic alterations in non-cirrhotic portal fibrosis, extrahepatic portal venous obstruction and Budd-Chiari syndrome. AB - We studied the coagulation function in ten patients each with non-cirrhotic portal fibrosis (NCPF), extrahepatic portal venous obstruction (EHPO) and Budd Chiari syndrome (BCS), conditions where venous thrombosis in the hepatic vasculature is a common denominator. Prothrombin time, partial thromboplastin time with kaolin (PTTK) and thrombin time were normal in patients with NCPF and EHPO. However, in BCS the PTTK was prolonged, with a mean test/control ratio of 1.68 +/- 0.11. Fibrin degradation products were absent in all patients. Platelet aggregation tests showed hypoaggregability in all patients with NCPF. They were normal in patients with EHPO. However, two of ten BCS patients showed hyperaggregability, coinciding with a recent onset of illness in one patient. In conclusion, coagulation abnormalities appear unlikely to be the cause of thrombosis in patients with NCPF and EHPO. Further studies are required to substantiate the findings of hyperaggregability of platelets in BCS. PMID- 2307503 TI - Antipyrine clearance: prognostic marker for obstructive jaundice. AB - A prospective study was undertaken to determine prognostic markers for patients with obstructive jaundice. Along with routine liver function tests, antipyrine clearance was determined in 20 patients. Four patients died after basal investigations. Five patients underwent definitive surgery. The remaining 11 patients were subjected to percutaneous transhepatic biliary decompression. Four patients died during the drainage period, while surgery was carried out for seven patients within 1-3 weeks of drainage. Of 20 patients, only six patients survived. Basal liver function tests were comparable in survivors and nonsurvivors. Discriminant analysis of the basal data revealed that plasma bilirubin, proteins and antipyrine half-life taken together had a strong association with mortality. A mathematical equation was derived using these variables and a score was computed for each patient. It was observed that a score value greater than or equal to 0.84 indicated survival. Omission of antipyrine half-life from the data, however, resulted in prediction of false security in 55% of patients. This study highlights the importance of addition of antipyrine elimination test to the routine liver function tests for precise identification of high risk patients. PMID- 2307504 TI - Adaptative changes in terminal ileum after total colectomy, mucosal proctectomy and straight ileo-anal anastomosis in chronic ulcerative colitis. AB - Total colectomy, mucosal proctectomy and straight ileo-anal anastomosis was performed in four adult patients with chronic ulcerative colitis (three males, one female; mean age 27.4 years). During a follow-up period of one to five years, all patients were continent, had spontaneous bowel evacuation (average 4-5 per day), and had normal bladder and sexual function. Sequential per rectal ileoscopies revealed loss of ileal folds and gradual transformation to a colonic type of mucosa. On barium studies, the anastomosed terminal ileum showed progressive ballooning and assumed a rectosigmoid appearance with complete disappearance of ileal characteristics. The histology showed a progressive transformation from ileal to colonic type of mucosa, with blunting and ultimate disappearance of villi, increasing goblet cell population, and increase in mononuclear cells in the lamina propria. Histochemical studies (high iron diamine and alcian blue stains) revealed a change from small intestinal to colonic mucin, progressing proximally from just above the anastomotic site. Two patients had a single recurrence with ileal histology resembling that of active ulcerative colitis; both responded to short term steroid therapy. The results of straight ileo-anal anastomosis compare well with Western reports of ileal reservoirs. Adaptative changes of 'colonisation' can be consistently demonstrated in the anastomosed ileum on follow-up; these start just above the anastomotic site and ascend proximally. The colonised ileum appears to be susceptible to the ulcerative disease. PMID- 2307505 TI - Spontaneous rupture of prolapsed rectum. PMID- 2307506 TI - Paroxysmal nocturnal hemoglobinuria with hepatic vein thrombosis presenting as hepatic encephalopathy. AB - We present a patient with paroxysmal nocturnal hemoglobinuria with diffuse hepatic central vein thrombosis who presented with encephalopathy and recovered from the hepatic manifestations with antihepatic coma measures alone. PMID- 2307507 TI - Hematemesis: a rare presentation of gastric volvulus. AB - Gastric volvulus is a rare condition. Upper gastrointestinal bleeding in gastric volvulus is extremely rare. We describe two patients with gastric volvulus who presented with upper gastrointestinal bleeding. PMID- 2307508 TI - Severe duodenal candidiasis in a patient with IgA deficiency and T cell defects. AB - Candida albicans was found to repeatedly colonise and invade the duodenal ulcer base in a 45 years old otherwise healthy patient receiving H2 receptor antagonists for a prolonged period. He had no delayed hypersensitivity to Candida skin test, and had T cell deficiency, abnormality in T cell blast transformation, defective macrophage migration inhibition factor (MIF) and IgA hypogammaglobulinemia. When treated with ketoconazole alone his ulcer healed completely. Ulcer scar biopsy and aspirates revealed no Candida and anti candidal antibodies disappeared from his serum. His T cell blastoid transformation, MIF and skin DTH to Candida were restored to normal levels, but IgA levels remained unchanged. Thus H2 receptor antagonists probably caused abnormalities in T helper cells leading to lymphokine unresponsiveness and subsequently loss of cellular immunity to candidal antigen. This combined with prior IgA immunodeficiency resulted into severe invasive candidiasis. PMID- 2307510 TI - Longitudinal shortening of esophagus in advanced corrosive injury. PMID- 2307509 TI - Obstructive jaundice due to chronic duodenal ulcer disease. PMID- 2307511 TI - Bile ascites following percentaneous trucut needle liver biopsy. PMID- 2307512 TI - In vitro association of leptospires with host cells. AB - Interactions of Leptospira interrogans with cultured endothelial and kidney epithelial cells were assayed by examining (i) cytoadherence of intrinsically radiolabeled leptospires to eucaryotic cell monolayers and (ii) penetration of leptospires through cell monolayers grown on polycarbonate filters in chemotaxis chambers. L. interrogans serovars attached to cultured cells in a dose- and time dependent manner. Adherence was diminished following pretreatment of organisms with proteases, rabbit immune serum, or heat. When observed by scanning electron microscopy, most leptospires attached by both ends, rather than just one tip like Treponema pallidum. In penetration assays, 9.7% of added L. interrogans migrated through the monolayer-filter barrier, while only 0.3% of L. biflexa penetrated in the same time interval. Transmission electron microscopy revealed that organisms entered the host cell cytoplasm. These in vitro results indicate that leptospires have an invasive capacity that may be related to pathogenicity in vivo and suggest that further investigation of interactions with host cells may enhance knowledge of leptospiral virulence. PMID- 2307513 TI - Transmembrane diffusion channels in Mycoplasma gallisepticum induced by tetanolysin. AB - The permeability properties of Mycoplasma gallisepticum cells treated with a purified preparation of tetanolysin were investigated by determining the initial swelling rates of cells suspended in an isoosmotic solution of electrolytes or nonelectrolytes. The swelling, initiated by the tetanolysin, depended on the tetanolysin concentration and was markedly affected by the molecular size of the various osmotic stabilizers utilized. Thus, the initial swelling rates in an isoosmotic solution of monosaccharides were much higher than those in isoosmotic solutions of di-, tri-, or tetrasaccharides. Cell swelling induced by tetanolysin was much lower with energy-depleted M. gallisepticum cells, with arsenate-treated cells, or when the membrane potential (delta psi) was collapsed by valinomycin (10 microM) plus KCl (100 mM). Swelling was not affected by the proton-conducting ionophore carbonyl cyanide-m-chlorophenylhydrazone (1 to 10 microM) or by nigericin (5 microM). These results support the concept that the damage induced by tetanolysin is due to the formation of water-filled pores within the membranes of energized M. gallisepticum cells. Such pores allow the diffusion of hydrophilic molecules into the cells and may vary in size, depending on the tetanolysin concentration utilized. PMID- 2307514 TI - Characterization of and human serologic response to proteins in Helicobacter pylori broth culture supernatants with vacuolizing cytotoxin activity. AB - Helicobacter pylori infection is strongly associated with histologic gastritis and peptic ulcer disease. Broth culture supernatants from a subset of H. pylori strains induce vacuolization in cultured cells, a phenomenon that has been attributed to cytotoxin activity. Concentrated culture supernatants from 15 of 28 (53.6%) H. pylori strains tested induced vacuolization in HeLa cells in titers ranging from 1:10 to 1:180. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining of supernatants from these 28 strains and 2 control strains demonstrated an 82-kilodalton (kDa) protein band in 3 of 16 supernatants with vacuolizing activity, but in none of 14 supernatants without vacuolizing activity. By immunoblotting with human sera, a 128-kDa band was recognized in all 16 supernatants with vacuolizing activity, compared with 9 of 14 (64%) supernatants without vacuolizing activity (P = 0.014). Serologic recognition of the 128-kDa band in H. pylori culture supernatants was more prevalent among persons infected with vacuolizing H. pylori strains than among persons infected with nonvacuolizing strains, but the difference was not statistically significant (80 versus 45%; P = 0.079); human serologic recognition of the 82-kDa band was less common. The 128-kDa band was recognized by 100% of 31 serum samples from H. pylori-infected patients with duodenal ulcer disease, compared with 60.8% of 74 serum samples from H. pylori-infected persons without peptic ulcer disease (P = 0.0001). These data indicate that antigenic 128- and 82 kDa proteins are present in H. pylori broth culture supernatants with vacuolizing activity and that serologic responses to the 128-kDa protein are more prevalent among H. pylori-infected persons with duodenal ulceration than among infected persons without peptic ulceration. PMID- 2307515 TI - Mortality and bacteriology of sepsis following cecal ligation and puncture in aged mice. AB - Epidemiologic data suggest that elderly adults are more susceptible to invasive bacterial infection by indigenous gut flora than are younger adults. The purpose of this investigation was to characterize a murine model of clinically encountered peritonitis in the aged. We subjected three different age groups (young, 16 weeks; mature, 12 months; senescent, 24 months) of C57BL/6NNia mice to surgically induced peritonitis by the cecal ligation and puncture procedure. Senescent mice died in a significantly shorter time following surgery than mature mice (median time to death, 24.4 versus 38.5 h, respectively; P less than or equal to 0.001). Blood, liver, spleen and occasionally, ceca were obtained at 2 and 12 h after the cecal ligation and puncture procedure and immediately following death, to characterize the bacterial kinetics of the model. Qualitative and quantitative aerobic, anaerobic, and coliform cultures were performed. No age related differences were found in the types of bacteria isolated throughout the time course of progressive sepsis. In mice in the mature and senescent age groups, at 2 and 12 h postsurgery, gram-negative anaerobes and gram-positive aerobes predominated in all tissues that were cultured. At the time of death, however, blood and tissue isolates consisted predominantly of coliform bacteria. The shift from mixed infection during sepsis to predominantly gram-negative bacterial infection reflected a similar progressive shift in bacterial types found in the cecum. At death, senescent mice had 100-fold fewer coliform bacteria in the bloodstream than those found in mature mice (2.5 x 10(9) versus 4.6 x 10(11), respectively). The increased sensitivity of aged mice to invasive bacterial infection documented in this series of experiments accords well with human epidemiologic experience and demonstrates the appropriateness of the model for continued investigations of sepsis in the aged. PMID- 2307516 TI - Sequence analysis of the gene for the glucan-binding protein of Streptococcus mutans Ingbritt. AB - The nucleotide sequence of the gbp gene, which encodes the glucan-binding protein (GBP) of Streptococcus mutans, was determined. The reading frame for gbp was 1,689 bases. A ribosome-binding site and putative promoter preceded the start codon, and potential stem-loop structures were identified downstream from the termination codon. The deduced amino acid sequence of the GBP revealed the presence of a signal peptide of 35 amino acids. The molecular weight of the processed protein was calculated to be 59,039. Two series of repeats spanned three-quarters of the carboxy-terminal end of the protein. The repeats were 32 to 34 and 17 to 20 amino acids in length and shared partial identity within each series. The repeats were found to be homologous to sequences hypothesized to be involved in glucan binding in the GTF-I of S. downei and to sequences within the protein products encoded by gtfB and gtfC of S. mutans. The repeated sequences may represent peptide segments that are important to glucan binding and may be distributed among GBPs from other bacterial inhabitants of plaque or the oral cavity. PMID- 2307518 TI - The 96-kilodalton antigen as an integral membrane protein in pathogenic Entamoeba histolytica: potential differences in pathogenic and nonpathogenic isolates. AB - A surface antigen (EH-96) of Entamoeba histolytica was demonstrated to be a plasma membrane antigen by immunoprecipitation of metabolically 35S-labeled antigen from live trophozoites, Triton X-114 detergent extracts, and plasma membrane-enriched fractions prepared by concanavalin A membrane stabilization and differential centrifugation. In addition, the antigen was localized to the plasma membrane by electron microscopy with colloidal gold. Antigen from E. histolytica strains immunoprecipitated with specific immunoglobulin M (IgM) or IgG2b monoclonal antibody was identical by one-dimensional peptide mapping with N chlorosuccinimide. Additionally, antigen from different axenically cultivated amebae was demonstrated to be identical by N-chlorosuccinimide peptide mapping, as were peptide maps of IgG and IgM monoclonal antibody-purified antigen. The 96 kilodalton (kDa) surface antigen was identified on four axenically cultivated pathogenic isolates and on three polyxenically cultivated pathogenic isolates (zymodeme II) of E. histolytica but was absent or present in lesser quantity on six nonpathogenic polyxenically cultivated isolates. The 96-kDa antigen was detected in liver abscess fluid from four patients with amebic abscesses by enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation. Two dimensional gel electrophoresis profiles of the 96-kDa antigen purified from abscess material or from polyxenically cultivated trophozoites demonstrated that the antigens were related to the 96-kDa antigen found in axenically cultivated organisms. PMID- 2307517 TI - Cryptosporidiosis in guinea pigs: an animal model. AB - Cryptosporidia from natural cryptosporidiosis in guinea pigs were experimentally transmitted to both adult and juvenile guinea pigs. Cryptosporidia were associated with the villi of the ileum, jejunum, and duodenum. Both juveniles and adults were equally susceptible to cryptosporidia, as determined by decreases in villus height, increases in crypt depth, and decreases in villus height/crypt depth ratios, when compared with uninoculated animals. When multiple paired comparisons were made between 2 and 10 days postinoculation, there were significant decreases in villus height/crypt depth ratios with time. A dose study showed that 6-week-old guinea pigs were all infected with doses as low as 325 oocysts per animal. When sampled at weekly intervals postinoculation, guinea pigs had significant evidence of infection up to 2 weeks but had recovered completely by 4 weeks. Guinea pigs mounted a specific humoral immune response against cryptosporidia, as measured by an immunoperoxidase technique. Guinea pigs challenged by reinoculation with cryptosporidial oocysts were completely refractory to reinfection. These studies show that cryptosporidiosis in guinea pigs is a useful small animal model of this disease. PMID- 2307519 TI - Nonreciprocal complementation of the hlyC and lktC genes of the Escherichia coli hemolysin and Pasteurella haemolytica leukotoxin determinants. AB - The genetic organization of the Pasteurella haemolytica leukotoxin operon (lktCABD) is similar to that of the Escherichia coli hemolysin (hlyCABD). Their gene products share a sequence similarity of 66, 62, 90.5, and 75.6%, respectively. We investigated the role of the C proteins (LktC and HlyC) by performing reciprocal transcomplementation analyses in an E. coli recombinant background. In the absence of the C genes, neither LktA nor HlyA had their respective cytotoxic activities. When hlyC was provided in trans to lktA, the toxin that was produced had the same activity and target cell specificity as the wild-type leukotoxin; it was leukotoxic for bovine lymphoid cells but not human lymphoblast cells when it was evaluated by a 51Cr-release assay. We also detected a weak hemolytic activity for the active form of LktA against sheep erythrocytes. In contrast, an E. coli strain containing lktC with hlyA produced a form of HlyA which was neither hemolytic nor cytotoxic. A monoclonal antibody (D12) against HlyA which recognized an epitope specific to the active form of HlyA did not cross-react in immunoblots with LktA that was activated by either LktC or HlyC. We conclude that the mechanism for activation of leukotoxin and hemolysin by their respective C proteins (LktC and HlyC) is mechanistically similar but that the exact structural requirements involved in the process are different. PMID- 2307520 TI - Muramic acid is not detectable in Chlamydia psittaci or Chlamydia trachomatis by gas chromatography-mass spectrometry. AB - By using the powerful separation technique of capillary gas chromatography combined with the selectivity of mass spectrometric detection, muramic acid was not detectable in purified elementary bodies of Chlamydia psittaci Cal 10 (less than or equal to 0.006%) or C. trachomatis serovar E (less than or equal to 0.02%). This confirms previous reports which suggested the absence of a typical peptidoglycan in Chlamydia spp. PMID- 2307521 TI - Size of the Streptococcus mutans GS-5 chromosome as determined by pulsed-field gel electrophoresis. AB - Rare cutting restriction endonucleases were used to cut the Streptococcus mutans chromosome into large fragments. Restriction enzymes utilizing recognition sites containing 6-, 7-, or 8-base-pair sequences with only G and C nucleotides produced few fragments, most of which were greater than 100 kilobase pairs in size. Addition of the fragments from digests of SmaI, NotI, ApaI, RsrII, and EagI yielded a molecular size for the S. mutans GS-5 genome of 2,819 +/- 60 kilobase pairs. PMID- 2307522 TI - Electron microscopic evidence for in vivo extracellular localization of Yersinia pseudotuberculosis harboring the pYV plasmid. AB - Electron microscopic evidence is presented that bacteria harboring the virulence plasmid pYV from Yersinia pseudotuberculosis are localized in extracellular sites during the course of infection in mice, often unambiguously undergoing active replication. Virulent pYV+ bacteria, often seen adherent to platelets, severely restricted granuloma formation, creating necrotic microabscesses poorly populated with inflammatory cells. This contrasts with granulomas produced by pYV- bacteria, which appear to be composed mainly of polymorphonuclear and mononuclear cells. Our results therefore strongly suggest that active replication of pYV+ bacteria predominantly, if not exclusively, occurs in vivo in extracellular sites. PMID- 2307523 TI - Motivating your patients: marketing dental services. AB - In most industrialized countries the issues of unemployment or under-employment are becoming more critical for the members of the dental associations. In some countries this is creating greater competition between the private practitioners and public health dentists as well as between private dental practitioners themselves. Modern marketing, especially service marketing theory and models, can provide dentists and dental associations with tools to improve their position in relation to patients, political decision makers and other public agencies. However, marketing has to be understood correctly as a philosophy providing a means of approaching the establishing, maintaining and enhancing patient or customer relationships and not as a narrowly defined set of tools. As long as marketing is considered to be external campaigns, such as advertising and not much else, it is bound to fail. Other dimensions of marketing, such as interactive marketing and internal marketing, are of much greater importance to dental practitioners. PMID- 2307524 TI - A radiographic four-year follow-up study of asymptomatic mandibular third molars in young adults. AB - Fifty-five asymptomatic mandibular third molars (M3) in 34 dental students (mean age 20.6 years at the start of the study) were followed radiographically for 4 years. Based on clinical evaluation the 55 teeth included 20 almost erupted, 13 partly erupted and 22 non-erupted M3. The following were assessed on the radiographs: root development, level of eruption, sagittal angulation, resorption, pericoronitis/bony pockets/paradental cysts and widening of the periodontal space/dentigerous cysts. The state of 21 teeth (38 per cent) was radiographically changed at the end of the observation period. The most remarkable finding was that 15 teeth changed their sagittal angulation, all in a distal direction; five mesioangular to vertical, five vertical to distoangular, five mesioangular to distoangular. Radiographically, 13 M3 moved to a more advanced level of eruption. No real pathological osseous lesions and no root resorption were observed at initial or follow-up examinations. It is concluded that there are frequent essentially unpredictable changes in the position of M3 after the age of 19 years which may influence decisions on their removal or preservation. PMID- 2307525 TI - Prevalence of dental fear in young adult Singaporeans. AB - One-hundred-and-fifteen male military recruits and 176 mostly female first- and second-year students in the National University of Singapore were surveyed regarding their fear of the dentist. Nine of 115 recruits and 36 of 176 university students were classified as having high fear, giving a population prevalence rate between 78 and 208 fearful young adults per 1000 population. Higher educational levels were associated with fear of the dentist. There were no significant racial differences in the prevalence rate in either sample. Higher fear scores were associated with longer intervals between dental visits for the university but not the military population. Efforts are needed to prevent and ameliorate the development of dental fears. Trust and control appear to be major factors associated with dental fears. PMID- 2307526 TI - Towards one dental world: systems and formatting for the electronic dental journal. AB - This paper discusses systems and format guidelines that can be used as a basis for evolving an agreement for publishing dental journal material on a compact laser read only memory (CD-ROM) disc. PMID- 2307527 TI - Alternative casting alloys for fixed prosthodontics. Federation Dentaire Internationale. Technical Report No. 34. PMID- 2307528 TI - Anthropometric variables and risk of breast cancer. AB - The role of anthropometric variables in the risk of breast cancer has been investigated using pooled data from 2 hospital-based case-control studies conducted in Italy for a total data-set of 3,247 cases and 3,263 controls. No association was observed in pre-menopausal women between breast cancer risk and height, weight, indices of body mass (W/H2; W/H1.5) and surface area. In post menopausal women, the risk of breast cancer was inversely related to height, being 0.8 in taller women (greater than 165 cm) compared with women 155 cm tall or less; the trend in risk, although not constantly decreasing, was statistically significant (p trend = 0.03). A direct, statistically significant association emerged with weight and indices of body mass and post-menopausal breast cancer risk. Considering 2 indices of body weight (W/H2 and W/H1.5) and relative to thinner women, the respective estimated risks of post-menopausal breast cancer increased to 1.4 and 1.3 for grossly obese women, and the corresponding p values for trend were respectively 0.002 and 0.02. The role of overweight was more evident in women with early age at menopause, thus suggesting a duration-risk effect. PMID- 2307529 TI - Cytosolic NAD(P)H:(quinone-acceptor)oxidoreductase in human normal and tumor tissue: effects of cigarette smoking and alcohol. AB - NAD(P)H:(quinone-acceptor)oxidoreductase (QAO), previously known as DT diaphorase, catalyzes the reduction of quinones to hydroquinones. Enhanced activity of the enzyme has been suggested to protect cells against the cellular toxicity and carcinogenicity of quinones, but may activate some cytotoxic anti tumor quinones. Cytosolic levels of QAO, carbonyl reductase (CR) and total quinone reductase activity have been measured in normal and tumorous human tissues. QAO was the major component of the total cytosolic quinone reductase activity in all the tissues investigated. CR represented 10 to 28% of the total cytosolic quinone reductase activity in normal tissue. Normal tissue QAO was high in the stomach and kidney, and lower in the lung, liver, colon and breast. Primary tumor from lung, liver, colon and breast had elevated levels of QAO compared to normal tissue, while tumor from kidney and stomach had lower levels. CR was not significantly altered in tumor tissue, except in the case of lung and colon tumor which showed an increase compared to normal tissue. A major determinant of the variability of human lung tumor QAO was the cigarette-smoking history of the donor. Non-smokers and past smokers had high levels of tumor QAO compared to normal tissue. Smokers had levels of tumor QAO that were not significantly different from those of normal tissue QAO. Smokers had a small increase in normal lung QAO compared to non-smokers. Alcohol use was associated with an increase in lung tumor QAO but had no effect on QAO in normal lung. The function of QAO in tumors is not known but the elevated activity of QAO in some tumors and the apparent depressant effect of smoking could influence the response of these tumors to quinone drugs or toxic agents that are metabolized by QAO. PMID- 2307530 TI - Metallothionein gene expression and resistance to cisplatin in human ovarian cancer. AB - Intracellular thiols have been proposed as mediators of resistance to alkylating agents and cisplatin. As metallothionein is the predominant protein thiol, we examined its relationship to cisplatin resistance in human ovarian cancer cell lines. A human ovarian carcinoma cell line, A2780, derived from an untreated patient, was treated with cisplatin in several ways and the induced resistance to cisplatin ranged from 13- to 68-fold. The degree of resistance was dependent upon the method of selection. The drug-resistant cell lines also developed low levels of cross-resistance to cadmium. Additional cell lines established from untreated patients or ovarian cancer patients refractory to cisplatin- and/or carboplatin containing combination chemotherapy were studied. The most cisplatin-resistant cell lines, OVCAR-8 and -10, were from patients previously treated with intensive chemotherapy. OVCAR-8 was relatively cross-resistant to cadmium while OVCAR-10 appeared relatively sensitive. Cell lines were examined for expression of metallothionein mRNA to evaluate the relationship between cisplatin resistance, cadmium cross-resistance and metallothionein expression. Only two of the cell lines with in vitro-induced resistance to cisplatin, 2780E80 and 2780CP70B3, had detectable metallothionein mRNA. The other cell lines selected in vitro for cisplatin resistance, as well as the parental A2780 ovarian cancer cell line, showed no expression at our level of detection. There was variable expression of metallothionein among the OVCAR cell lines. Cell lines from untreated patients, OVCAR-5 and -7, did express metallothionein, while the most cisplatin-resistant cell lines, OVCAR-8 and -10, did not. We also examined cisplatin induction of metallothionein mRNA in the cell lines. Only 2780CP70B3 among the cell lines with in vitro-induced cisplatin resistance showed increased expression after short term exposure to cisplatin. OVCAR-4 also had a slight increase in expression after exposure to cisplatin. Mouse C127 cells transfected with a bovine papilloma virus-metallothionein gene construct were compared for cisplatin sensitivity to the same cell type transfected with bovine papilloma virus alone. In this model system, metallothionein expression did not influence cisplatin cytotoxicity. On the basis of these studies, we conclude that there is no causal relationship between metallothionein expression and cisplatin resistance. PMID- 2307531 TI - Hodgkin's disease in adults: association with social factors and age at tonsillectomy. A case-control study. AB - The relationship between socio-economic characteristics, previous tonsillectomy, family history of cancer and risk of Hodgkin's disease (HD) was investigated in a case-control study. One hundred and sixty patients, aged 15-78, with histologically confirmed HD, and 185 hospital controls were interviewed. A statistically significant decrease in risk of HD was observed among subjects with large sibship size (RR = 0.63, C.I. 0.46-0.86) and among those who underwent tonsillectomy prior to the age of 10 (RR = 0.46, C.I. 0.22-0.94). High educational level was associated with an increased risk of HD (RR = 6.68, C.I. I.94-23.08). Analysis by age-group (15-39 yrs and 40 yrs or more) confirmed the role of high educational level as a risk factor in both young and old subjects, while the protective effect of tonsillectomy at an early age seems to be confined to young subjects. Analysis by histological subtype showed a statistically significant decrease in risk of HD in large sibship size for both nodular sclerosis (NS) and mixed-cell subtypes; the role of education and tonsillectomy was observed only for NS. These data confirm the role of social factors in HD risk and suggest a protective effect of tonsillectomy performed early in life that needs to be confirmed in larger population-based studies. PMID- 2307532 TI - Age at first and second births and breast cancer risk in biparous women. AB - The role of age at first and at second birth on subsequent breast cancer risk was analyzed using pooled data from 2 hospital-based case-control studies conducted in Italy, for a total of 1,200 biparous cases and 987 controls. Compared with women who gave birth for the first time below age 20, the relative risks were above unity for those with later first birth, even after allowance for age at second birth, although the trend was inconsistent across subsequent strata. A similar direct trend in risk was observed in relation to age at second birth: compared with less than 25 years and after allowance for age at first birth, the point estimates were 1.2, 1.4 and 1.4 for 25-29, 30-34 and greater than or equal to 35 (p for linear trend = 0.04). The results for age at first and at second birth were similar in the 2 studies pooled in this analysis. A significant interaction with age was observed in relation to age at first and at second birth. In younger women (below age 50) a strong and direct association with age at first birth was found, while no apparent protection was conveyed by earlier second birth. Among older women (aged 50 or over), there was no apparent relationship with age at first birth after allowance for age at second, but the role of age at second birth was independent and statistically significant. Thus, our study confirms an independent and significant role of age at second birth in biparous women, after allowance for age at first birth, and indicates that, after reciprocal allowance, the role of first and second birth was not apparently different. The relative risks for both variables were quantitatively moderate, and may be influenced by age or other temporal variables. PMID- 2307533 TI - The locus of the polymorphic epithelial mucin (PEM) tumour antigen on chromosome 1q21 shows a high frequency of alteration in primary human breast tumours. AB - Tumour and blood leukocyte DNAs from sporadic breast cancer patients were examined for chromosome 1 loss of heterozygosity using a probe for a polymorphic epithelial mucin, PEM, which is expressed in greater than 92% of breast carcinomas as well as in normal lactating breast tissue. Expression is detected by the monoclonal antibodies (MAbs) HMFG-1, -2 and SM-3 which react with epitopes in the 20 amino-acid repeat unit of the core protein. The PEM probe has been mapped to the chromosome band 1q21, a region that is often incriminated in chromosomal rearrangements in breast tumours. Loss of heterozygosity or alteration at the PEM locus was detected in 34% of the 70 informative patients examined. Twenty of the 24 individuals showed loss of an allele, whereas 4 showed gain of an additional allele or amplification of an existing allele. Twenty-eight percent of informative cases exhibited alterations at the MS32 locus, 1q42-43, and 20% had alterations at the short arm locus MS1 at 1p33-35. These findings identify the long arm of chromosome 1 and in particular the region around the PEM gene for localization of a gene whose loss or alteration may, in some tumours, contribute to the progression of disease in breast cancer patients. PMID- 2307534 TI - Cancer mortality among Japanese residents of the city of Sao Paulo, Brazil. AB - Death certificates of Japanese residents of the city of Sao Paulo, Brazil from 1979 to 1981 were analyzed for cancer deaths by means of the standardized mortality ratio (SMR) and the standardized proportional mortality ratio (SPMR). Compared with residents of Japan, a significantly higher SMR value was obtained from Japan-born residents of Sao Paulo for prostate cancer, whereas lower values were obtained for cancer of the liver and gall-bladder in both sexes, of the esophagus and rectum in males, and of the lung in females. SMR values were higher for cancer of the stomach in both sexes but lower for those of the esophagus and prostate in males and of the gall-bladder and breast in females, when compared with the general population of Sao Paulo. Among Japan- and Brazil-born residents, stomach cancer in women revealed a significant stepwise decrease by generation when SPMR was used as an indicator. The high proportion of stomach cancer in males, however, was as high among the Brazil-born generation as in Japan. The SPMR of liver cancer decreased to the low level of the general population of Sao Paulo, even among the first generation. These changes in cancer patterns are discussed in relation to those among Japanese residents in the United States. PMID- 2307535 TI - Body mass index and risk of breast cancer. A prospective study of 23,826 Norwegian women. AB - The association between body mass index (BMI) and the incidence rate of breast cancer has been examined in 236 cases of breast cancer that developed among 23,826 Norwegian women during 11 to 14 years of follow-up. At the time of height and weight measurement they were 35 to 51 years of age, and at the end of follow up their age was between 46 and 63 years. There was an overall age-adjusted incidence rate ratio (IRR) of 0.52 (95% confidence limits, 0.34 and 0.77) for women in the highest quartile of BMI compared to women in the lowest quartile, which was confined to an effect observed among women who were diagnosed at age 50 or earlier (IRR = 0.36). The association with BMI displayed an inverse dose related trend (chi 2 for trend = 14.22, p less than 0.001). The negative trend was particularly pronounced among non-smoking women (chi 2 = 14.63), and no clear trend associate with BMI was observed among women who smoked 10 or more cigarettes per day (chi 2 = 0.41), indicating an interaction between BMI and cigarette smoking (chi 2 interaction = 3.86, p = 0.05). We thus suggest that there is a negative association between body mass index and risk of breast cancer among premenopausal women. PMID- 2307536 TI - Lymphocytic infiltration and cytotoxicity under hypoxic conditions in the EMT6 mouse mammary tumor. AB - Infiltration of lymphocytes, neutrophils and macrophages was evaluated in hypoxic and well-oxygenated areas of the EMT6 mouse mammary adenocarcinoma, by in vivo staining with the fluorescent dye Hoechst 33342 followed by cell sorting on the basis of fluorescence intensity. Tumors were grouped by days post-injection (days 11-14, 15-17 and 20-27). As lymphocytes are the only host cell population in this tumor model to possess lytic activity against EMT6 tumor cells, the ability of sensitized T lymphocytes to lyse syngeneic EMT6 cells was examined under conditions of varying oxygen concentrations. Infiltrating lymphocytes were detected to the same extent in cell fractions from both areas in all tumors. In contrast, neutrophils were found in significantly higher percentages in the hypoxic population than in the well-oxygenated cell fraction of all but the largest tumors. Macrophages were present in significantly higher percentages in the well-oxygenated fraction than in the hypoxic fraction of day-11 to -14 tumors. Extreme radiobiological hypoxia (0% O2) resulted in a significant decrease in T-cell-mediated lysis of EMT6 tumor cells, compared to lysis in room air (20% O2), but lysis was not impaired under conditions of mild radiobiological hypoxia (1% O2). Our study indicates that host-cell infiltration into areas of differing oxygenation may be quantitated via in situ Hoechst staining followed by cell sorting; in the EMT6 tumor, lymphocytes appear to infiltrate hypoxic areas to the same extent as well-oxygenated areas, and T-lymphocyte killing of syngeneic tumor cells is significantly reduced, although still present, under these hypoxic conditions. PMID- 2307537 TI - Transcriptional down-regulation of the rearranged C-myc expression in murine cell hybrids between a plasmacytoma and a T-cell lymphoma. AB - Regulation of the rearranged and non-rearranged c-myc expression was studied in murine cell hybrids (SBWI and SBWII) between plasmacytoma (S194) and T-cell lymphoma (BW5147) cells. Expression of the rearranged c-myc of heterogeneous mRNA sizes (1.8 approximately 2.4 kb) was markedly down-regulated in these hybrids regardless of retention of the gene. On the other hand, expression of the non rearranged c-myc (2.4 kb) was not significantly affected in these hybrids. Treatment of SBWI hybrid cells with cycloheximide enhanced the non-rearranged c myc 2- to 4-fold but did not release the down-regulation of the rearranged c-myc at all, suggesting that the down-regulation of the rearranged c-myc in the hybrid cells was mainly at a transcriptional rather than a post-transcriptional level. This was supported by the results of nuclear run-on assay: the high level of run on transcripts in S194 cells declined in SBWI hybrid cells comparable to the level in BW5147 cells. The rearranged c-myc was hemi-methylated in S194 cells and the pattern was the same in SBWI hybrid cells. Furthermore, down-regulation of the rearranged c-myc in the hybrid was also not restored by treatment with 5 azacytidine (5-AzaC), 12-O-tetradecanoylphorbol-13-acetate (TPA) or forskolin, suggesting no causative involvement of DNA methylation or protein phosphorylation in down-regulation. Higher DNase I sensitivity of the rearranged c-myc in S194 cells decreased to a similar extent to that of the non-rearranged c-myc after cell fusion with BW5147 cells. These results suggest that expression of the rearranged c-myc is down-regulated at the level of transcription in murine cell hybrids between a plasmacytoma and a T-cell lymphoma, probably by changing chromatin configuration around the gene from the open to the closed state. PMID- 2307538 TI - Disseminated or localized growth of a human B-cell tumor (Daudi) in SCID mice. AB - A human Burkitt lymphoma (Daudi) has been grown in the mutant mouse called C.B-17 SCID. Twenty-eight days after s.c. injection of Daudi cells, a palpable tumor grew only at the site of injection in all injected mice. In contrast, after intravenous (i.v.) or intraperitoneal (i.p.) injection, macroscopic, disseminated tumors developed. Following i.v. inoculation, tumors grew in the lungs, kidneys, ovaries and adipose tissue, and microscopic tumor infiltrates were observed in the spleen, bone marrow, spinal column and femur, whereas after i.p. injection, the tumors were localized in the abdomen, liver, spleen, ovaries and muscular tunics of the gut, but did not disseminate into the lung or bone marrow. The growth pattern and phenotype of the Daudi cells were similar whether the inoculated tumor cells were derived from the in vitro cell line or from in vivo passaged tumors. The survival time of the tumor-bearing animals was dependent on the dose of i.v.-administered Daudi cells; as few as 100 cells caused death. All mice injected i.v. showed paresis or paralysis of the hind legs just prior to death. This was associated with the presence of neoplastic nodules within the spinal canal. Two surface antigens on Daudi cells (CD19 and CD22) were stably expressed in all the neoplastic lesions. Radiolabelled anti-CD22 antibodies localized in organs infiltrated with tumor, but did not penetrate primary s.c. tumors. This model of disseminated vs. solid tumor should prove useful for evaluating the efficacy of different types and doses of therapeutic antibodies, immunoconjugates and immunotoxins prepared from anti-human B-cell antibodies. PMID- 2307539 TI - Inhibitory effects of 9-(2-phosphonylmethoxyethyl)adenine and 3'-azido-2',3' dideoxythymidine on tumor development in mice inoculated intracerebrally with Moloney murine sarcoma virus. AB - 9-(2-Phosphonylmethoxyethyl)adenine (PMEA), a potent inhibitor of human immunodeficiency virus (HIV), caused a dose-dependent suppression of tumor formation, and mortality associated therewith, in 6-day-old NMRI mice inoculated intracerebrally with Moloney murine sarcoma virus (MSV). Even at a dose as low as 1 mg/kg/day, PMEA effected a significant delay in tumor formation. When evaluated in parallel with PMEA, 3'-azido-2',3'-dideoxythymidine (AZT) conferred a comparable tumor-inhibitory effect at a 5- to 10-fold higher dose than PMEA. Prolonged treatment of MSV-infected mice with PMEA resulted in long-term survivors without apparent signs of tumor development. In view of the propensity of HIV to spread to the central nervous system (CNS), the marked activity shown by PMEA against experimental retrovirus infection of the brain in mice points to its potential in the treatment of AIDS and other retrovirus infections of the CNS. PMID- 2307541 TI - Cessation of autonomous proliferation of mouse lymphoma EL4 by fusion with a T cell line. AB - Benzanthracene-induced C57BL/6 (H-2b) mouse T-cell lymphoma EL4 (a thymidine kinase-deficient cell line) was fused by using polyethylene glycol with an Mlsa (Mls for minor lymphocyte stimulatory) antigen-dependent T cell line, which was designated G4 and had been derived from a C3H/He mouse (H-2k), and the fused cells were cultured in HAT medium. Although no growing cells appeared in most of these fusions, we consistently obtained growth-arrested H-2Kb-positive cells from the fused cell populations by the panning method. The cells were tetraploid and were able to proliferate in response to Mlsa antigen. Three H-2Kb-positive clones, isolated by limiting dilution from three different fusions, were shown to be EL4 x G4 hybrids, because (1) they had both H-2k and H-2b antigens; (2) each of the clones had one submetacentric chromosome which was a marker chromosome of EL4, and they were tetraploid with modal chromosome numbers of 74, 78, and 79, respectively; (3) they had 4 isozymes of both parental cells. These results indicate that EL4 lymphoma cells cease to proliferate when fused with T cell line G4. The malignant phenotype of lymphoma EL4 is thus suppressed at the level of cell transformation by the introduction of the G4 cell genome. PMID- 2307540 TI - Differences in c-myc and pvt-1 amplification in SEWA sarcoma sublines selected for adherent or non-adherent growth. AB - Conversion of solid sarcomas and carcinomas into ascites tumors depends on the in vivo selection of phenotypically altered tumor cell variants that can grow in the dissociated form. Once selected, they retain this property even after prolonged s.c. growth as solid tumors. From an s.c.-passaged subline of an ascites converted murine sarcoma (SEWA-AS12), we were able to separate cells adapted to the ascites form of growth from cells that can only grow in the solid form on the basis of their differential adherence to plastic. Both c-myc and pvt-1 were amplified approximately 63- to 77-fold in the nonadherent subline (SEWA-AS12-NA), but only 5- to 8-fold in the adherent subline (SEWA-AS12-ADH). This suggests that c-myc and/or pvt-1 amplification may provide a selective advantage to cells that can grow in the dissociated form. PMID- 2307542 TI - DEL cell line: a "malignant histiocytosis" CD30+ t(5;6)(q35;p21) cell line. AB - A new cell line DEL, established in vitro, was isolated from a pleural effusion of a boy who died of malignant histiocytosis. Its principal characteristics are: strong positivity with monoclonal antibodies (MAbs) to CD25, CD30, CD45R, KiM7, EMA, HLA Cl I and II; constant presence of acid phosphatase, ANAE, alpha-anti trypsin, alpha-anti-chymotrypsin and NBT reductase activity; rearrangement of the immunoglobulin heavy-chain gene (JH) and a germ-line configuration of the T-chain gene; and finally a translocation between chromosomes 5-6 with a breakpoint in 5q35. The DEL cell line is appropriate for studying the role of the 5q localized c-fms oncogene and of the genes of the mononuclear phagocyte growth factor (CSFI) and of their receptors in the dynamics and etiology of malignant hemopathies associated with a 5q35 breakpoint. PMID- 2307543 TI - Suramin inhibits proliferation of rat glioma cells and alters N-CAM cell surface expression. AB - Suramin, a drug used in the treatment of trypanosomiasis and onchocerciasis inhibits growth-factor-induced mitogenesis. We have investigated the effect of suramin on the growth rate and the morphology of C6 glioma cells cultured in the presence of serum or in a serum-free defined medium. Exponentially growing cells were seeded in multi-dish plates (5 x 10(4) cells/2 cm2 well) in DMEM supplemented with 5% fetal calf serum and were continuously exposed to 1 microgram/ml to 1,000 micrograms/ml suramin. Growth rate (determined 9 days after seeding) was reduced by 5%, 33%, 56% and 97%, respectively for suramin concentrations of 1, 10, 100 and 1000 micrograms/ml. Similar results were obtained in serum-free defined medium (DMEM/F12, 1:1, v:v, EGF 5 ng/ml, transferrin 5 micrograms/ml, selenium 10 ng/ml). Moreover, the concentration of suramin in the culture medium remained constant, demonstrating that the drug was not actively metabolized by the cells. Suramin also induced marked changes in cell morphology: the usual bipolar shape of C6 cells evolved toward a more differentiated appearance, with numerous cellular processes allowing a wide number of cell-cell contacts. In parallel, we monitored expression of an adhesion molecule (N-CAM) at both the mRNA and protein levels. Indirect immunofluoresence technique showed an important increase in cell surface N-CAM expression, starting from a dose of 10 micrograms/ml suramin, whereas total cellular content of N-CAM protein as well as its mRNA levels were unaffected. We also observed that the levels of expression of actin and N-CAM mRNAs decreased by a factor of two in cells maintained in defined medium. However, the relative ratio of N-CAM mRNA over actin mRNA was virtually unchanged following suramin treatment. Taken together, our results suggest that suramin (i) exerts a blocking effect of autocrine growth factors, (ii) interferes with the turn-over mechanisms of N-CAM expressed at the cell surface, either by impairing its endocytosis and/or the process of release of the N-CAM 120 isoform. PMID- 2307544 TI - Further characterization, isolation and identification of the epithelial cell surface antigen defined by monoclonal antibody AUA1. AB - The human epithelial antigen recognized monoclonal antibody (MAb) AUA1 has been characterized as a cell-surface glycoprotein. It has been isolated from human colonic mucosa by AUA1 affinity separation. N-terminal peptide sequence of this purified material has revealed a 17 amino acid sequence which identifies it with one of a group of similar epithelial/tumor-associated glycoproteins defined by a variety of MAbs. Using the polymerase chain reaction to map the gene encoding this antigen, our previous AUA1 antigen assignment to chromosome 2 has been confirmed. PMID- 2307545 TI - Evidence of loss of N-myc amplification during the establishment of a human neuroblastoma cell line. PMID- 2307546 TI - Gene transcription: a role for nuclear protein kinase C? PMID- 2307547 TI - Incidence of colo-rectal cancer in Moscow. PMID- 2307548 TI - A distribution-free procedure for the statistical analysis of bioequivalence studies. AB - In bioequivalence assessment, the consumer risk of erroneously accepting bioequivalence is of primary concern. In order to control the consumer risk, the decision problem is formulated with bioinequivalence as hypothesis and bioequivalence as alternative. In the parametric approach, a split into two one sided test problems and application of two-sample t-tests have been suggested. Rejection of both hypotheses at nominal alpha-level is equivalent to the inclusion of the classical (shortest) (1-2 alpha) 100%-confidence interval in the bioequivalence range. This paper demonstrates that the rejection of the two one sided hypotheses at nominal alpha-level by means of nonparametric Mann-Whitney Wilcoxon tests is equivalent to the inclusion of the corresponding distribution free (1-2 alpha) 100%-confidence interval in the bioequivalence range. This distribution-free (nonparametric) approach needs weaker model assumptions and hence presents an alternative to the parametric approach. PMID- 2307549 TI - Antihypertensive therapy with ketanserin: effects on central and renal hemodynamics, and microalbuminuria. AB - Ten patients with essential hypertension and normal renal function were treated with ketanserin (20-40 mg twice a day), administered for 8 weeks. In all patients, the changes in systemic and renal hemodynamics, and in urine albumin excretion, were assessed. Ketanserin monotherapy effectively lowered blood pressure in all patients. No change in cardiac output, pulse rate and stroke volume was observed; peripheral vascular resistance was significantly decreased. Plasma volume was unaltered. Renal plasma flow, glomerular filtration rate and filtration fraction were stable, with a slight but not significant reduction in renal vascular resistance. Urine albumin excretion remained unchanged. No relevant side effects were observed during the treatment period. In conclusion, our results confirm that ketanserin alone is an effective antihypertensive agent in patients with uncomplicated essential hypertension. The blood pressure lowering effect is mainly due to the systemic vasodilatation; renal hemodynamics and function are well preserved. PMID- 2307550 TI - Analysis of uric acid transport in renal tubules using benzbromarone and pyrazinamide. AB - Both the benzbromarone loading test alone and the pyrazinamide suppression test combined with the benzbromarone loading test were performed in four healthy male volunteers to examine the renal handling of uric acid and to demonstrate whether benzbromarone selectively blocks postsecretory reabsorption. On the basis of the four-component theory, equations of four states of fractional uric acid clearance were constructed: 1) the control state, the states of 2) benzbromarone loading, 3) pyrazinamide suppression and 4) both pyrazinamide suppression and benzbromarone loading. As a result, presecretory reabsorption, tubular secretion and postsecretory reabsorption of uric acid were calculated to be about 93-98%, 30-44% and 79-92%, respectively. In addition, it was calculated that benzbromarone inhibited postsecretory reabsorption selectively. Because of the selectivity of the action site of benzbromarone in renal tubules, this loading test is considered to reflect uric acid transport more precisely than tests using probenecid. PMID- 2307551 TI - Beyond our means: patterns of variability of physiological traits. AB - Epidemiologists usually employ measures of variability of physiological traits such as blood pressure and cholesterol only to determine confidence intervals or statistical significance. For evolutionary biologists population variability per se has proven of interest. This article explores the applicability of this perspective to the analysis of human physiology, using data from the Framingham Heart Disease Study and the National Health and Nutrition Examination Surveys. The nonrandom patterns of variability observed suggest that examination of the degree and pattern of heterogeneity within a population may provide information not evident from the analysis of mean values. PMID- 2307552 TI - The effects of system characteristics on policy implementation and functioning of care for the elderly in France. AB - In the early 1960s, old age in France was replaced by the notion of "troisieme age," a new definition stressing the possibility of pursuing social and leisure activities and greater independence. Old age itself was postponed to a later age, and acquired a purely negative image and one confused with that of incurable illness. As a result, a living-at-home policy was elaborated, and also a program of adapting institutions to the problems of those now defined as being in the "quatrieme age." This dual-faceted medicosocial policy was originally intended to be comprehensive and coordinated. Analysis of the structural characteristics of the care providers and of the agencies responsible for organization and financing of services shows fragmentation at the levels of service delivery and policy development. This prevents the coordination of service provision, gives rise to a mismatch between people and provision, and leads to a lack of coherent regulation and of adequate financing, in particular with regard to domiciliary care and social services. External factors, such as scarcity of funds related to the economic crisis, reinforce system dysfunctions. PMID- 2307553 TI - Tuberculosis and social stratification in South Africa. AB - Tuberculosis (TB) continues to be a barometer of poverty, determined by racial classification, in both town and countryside in the Republic of South Africa. Despite the fact that whites with the disease stand a greater chance of being diagnosed than their black counterparts, because they have very much better access to health care, the risks of TB for people classified by the state as black and colored are 27 and 16 times, respectively, the risk for whites. Black gold miners, the nutritional elite of the workforce, have also experienced an increase in TB rates. Tuberculosis accounts for 50 percent of all black compensation cases and some 2.5 percent of white cases. The risks of TB have increased over recent years among colored and blacks. Rates of tuberculous meningitis have also increased over the past decade, and show the dramatically worse health care available to people classified as black and colored. Although about 60,000 new TB cases are reported in the country each year, there have been cutbacks in the resources available for TB control and treatment. PMID- 2307554 TI - Planning for primary health care: the case of the Sierra Leone National Action Plan. AB - The National Action Plan for Primary Health Care, a planning document of the Sierra Leonean Ministry of Health for the restructuring of the country's rural health services, is analyzed in its social, economic, and historical context. It appears to be an attempt of the national government to gain control over the highly devolved health care delivery system, but the state has neither the political will nor the power to achieve this goal. The utility of the document is therefore in doubt, which raises two important questions: Whose interests does this plan serve, and at whose cost? PMID- 2307555 TI - The World Medical Association serves apartheid. PMID- 2307556 TI - Structural changes, ill health, and mortality in Sweden, 1963-1983: a macroaggregated study. AB - An exploratory time series analysis was performed on selected indicators of structural change, health behavior, and ill health in Sweden in the years 1963 1983. Both synchronic (nonlagged) and asynchronic (lagged) analyses were made. The synchronic analysis of variations in the suicide rate reveals two main contributory factors: level of employment and overtime work. For cardiovascular mortality in men, the synchronic and the two-year time lagged analyses reveal that the sale of alcohol and, to a certain extent, the length of the period of unemployment play a major role. In an analysis with a three-year time lag, only one significant factor for both men and women is revealed, namely the level of employment. In the synchronic analysis of cirrhosis mortality in men, the sale of alcohol plays a dominant role. The results of the synchronic analysis of the variations in sick leave show a similar pattern for both men and women. In both cases, the sale of alcohol is positively associated and the proportion of unemployed industrial workers negatively associated with sick leave. The results give rise to a number of questions. For example, how should these findings be interpreted and how should they be related to existing knowledge about the links between business cycles and changes in the health of the population? The answers to such questions are of importance both from a scientific viewpoint and with regard to health policy. We argue that the answers require further studies of the characteristics of the periods in the business cycle and of how these periods affect people's lives, living conditions, and behavioral patterns in general. PMID- 2307557 TI - [Arthritis following sexual contact]. PMID- 2307558 TI - [Recurrent hypertensive crises and dyspnea following unilateral adrenalectomy in pheochromocytoma in a 44-year-old patient. Successful combination chemotherapy of malignant pheochromocytoma]. PMID- 2307559 TI - [Treatment of arthrosis]. PMID- 2307560 TI - Efficient recovery of clonogenic stem cells from solid tumors and occult metastatic deposits. AB - We describe the use of enzymes combined with brief, sequential mechanical disruptions in a Tekmar Stomacher blender for the recovery of clonogenic neoplastic cells from solid tumors, lungs, and livers. The method has yielded 3 X 10(8) to 5 X 10(8) total cells and 1.2 X 10(6) to 17 X 10(6) clonogenic cells per gram of tissue from three different mouse mammary tumor subpopulations growing in the subcutis. The clonogenic cell yields represent a 4- to 13-fold increase over our previous best method of tumor disaggregation. The increase in total cells recovered, while not as dramatic (up to 3-fold), was statistically significant for two of the three tumor lines. We were also able to efficiently recover 125I iododeoxyuridine labelled neoplastic cells from lungs and livers after injecting the cells intravenously. Over half of the total radiolabel present in these organs prior to disaggregation could be recovered in the cell suspensions obtained. PMID- 2307561 TI - Interactions between human glioma cells and fetal rat brain aggregates studied in a chemically defined medium. AB - The in vitro invasive growth of two continuous human glioma cell lines (D-54Mg and GaMg) into aggregates of fetal rat brain cells is described. The tumor cells were first cultured as multicellular tumor spheroids and thereafter cocultured with brain aggregates in medium agar cultures. Two different types of culture media were used for the propagation of spheroids and for coculture experiments: Dulbecco's modified Eagle's medium supplemented with 10% newborn calf serum, and Costar SF-X chemically defined hybridoma medium. Both cell lines showed invasive growth into brain tissue in both types of media. Apart from progressive destruction caused by the malignant cells, the brain aggregates maintained characteristics of neural tissue. One cell line (D-54Mg) showed reduced invasiveness in chemically defined medium as measured with a grading system to quantify invasion. The coculture system may represent a basis for studying invasion of human glioma cells in brain tissue under defined chemical conditions. PMID- 2307562 TI - Association between MHC class I antigen expression and malignancy of murine T lymphoma variants. AB - Tumor cell variants were derived from an AKR T-cell lymphoma cell line (BW5147, H 2k haplotype). These variants differed in their malignant potential and in their membrane expression of class I MHC antigens. High tumorigenic and spontaneous metastatic capacity was found to be predominantly associated with a decrease of H 2Kk class I major histocompatibility complex (MHC) antigen expression. In contrast, high experimental metastatic capacity correlated strongly with an increased H-2Dk antigen expression. The in vitro invasive potential and the LFA-1 expression of the BW variants showed no correlation with the differential MHC antigen expression and the differential metastatic and tumorigenic capacity of the BW variants. Furthermore, the susceptibility of the BW 5147 variants to TNF and NK-mediated cytotoxicity was not related to the differential metastatic potential and the expression of the class I MHC antigens. PMID- 2307564 TI - Peer education IPS goal. PMID- 2307563 TI - A new test to measure homotypic aggregation of human tumour cells. AB - A method is described for quantitative measurements of homotypic aggregation by sequential passaging of cells through several gauze nets with different mesh width. This method allows rapid and simple determination of the size distribution of the formed aggregates with little cost. Time course and the effects of divalent cations, sugars and of enzyme treatment on homotypic aggregation were examined in detail for the human colon carcinoma line HT29, but also aggregation of human neuroblastoma, leukemic promyelocytes HL60, and of murine lymphoma cells was studied. Crude membrane fractions prepared from several colon carcinoma cells and from dissociated human colon tumour tissue showed strong aggregation promoting effects when incubated with HT29 cells. Determination of lectin-induced agglutination of HT29 cells by means of the proposed method demonstrated that HT29 carries high numbers of binding sites for Ricinus communis agglutinin, wheat germ agglutinin, Ulex europeus agglutinin and Griffonia simplicifolia I isolectin A4. These results were supported by direct microanalytical determination of membrane-bound sialic acid and total fucose. PMID- 2307565 TI - Peer review: indictment, trial and beyond. PMID- 2307566 TI - Late life psychoses. AB - The need for new diagnostic tools is illustrated in this discussion of elderly patients who develop psychoses secondary to organic brain syndromes. PMID- 2307567 TI - Cholinesterase risk for Iowa farmers. AB - Exposure to organophosphate insecticides may pose a significant risk in rural populations. The study involved 71 Iowa farmers and 28 agribusiness workers who underwent serial measurements of serum cholinesterase levels prior to and following exposure to organophosphate containing pesticides. PMID- 2307568 TI - The case of the man with bleeding gums. PMID- 2307569 TI - Concern for the mentally ill. PMID- 2307570 TI - Ethics in CME. PMID- 2307571 TI - Severity ratings and quality concerns. PMID- 2307572 TI - The geriatric market. PMID- 2307573 TI - Sustained-release dosage forms. PMID- 2307574 TI - Annual immunization audit. PMID- 2307575 TI - Artificial intelligence: a technology review. PMID- 2307576 TI - Artificial neural systems. PMID- 2307577 TI - Multivariable alarming using neural networks. AB - The monitoring and alarming of processes is normally done in one dimension. Each measurable parameter is treated as independent of all others. The only time this is not true is when the dynamics of a multivariable process are "modeled" using equations that predict the chemical, physical, and/or thermodynamic properties of the process in terms of these parameters. Unfortunately, this requires that the relationship be known and accurately describable in mathematical terms. Using neural networks to map the "N"-space relationship among a set of "N"-variables, it is possible to create experience-based "models" of the multivariable relationships. This technique does not require that the relationship even be known, only that a "live" process be available to "teach" the neural network the various safe and unsafe states of the process. PMID- 2307578 TI - Hydralazine causes nonspecific binding of antibodies to human lymphocytes in vitro. AB - In vitro incubation of human lymphocytes or a continuous human Jurkat T cell line with hydralazine (1-hydrazinophthalazine), a widely used antihypertensive agent, produced a nonspecific binding of various antibodies to the cells. This phenomenon was found to produce increases in staining of mitogen-stimulated and mitogen-unstimulated human lymphocytes and Jurkat cells with a variety of antibodies recognizing T and B cell antigens. The increase in nonspecific binding was greatest at 10(-2) M hydralazine, but was seen with concentrations as low 10( 7) M, which is comparable to the serum concentrations of patients prescribed hydralazine. The binding of antibodies is not connected with significant decreases in the cell viability. This property of hydralazine may cause misinterpretation of certain immunological tests employing the antibodies. PMID- 2307579 TI - Rheumatoid factor induction in the mouse: sex differences and the effect of the sex steroids. AB - Female CBA mice produced a significantly higher plasma rheumatoid factor (RF) response to Salmonella typhosa lipopolysaccharide than did male mice. The peak level in females was observed on day 5-6 after injection and in males on day 7-8. Elevated RF levels continued to be detected more than 30 days later. A second injection of LPS, 38 days after the first, to assess the secondary response, had no more than an additive effect on plasma RF concentration, although the day of peak response was earlier by two days in both sexes. Administration of oestradiol 17 beta by Silastic implant brought forward the day of peak response by two days in both sexes although it reduced its amplitude considerably. Testosterone had little effect on the peak concentrations achieved in both sexes, but did produce a slower decay in plasma RF level. This investigation indicates that the sex hormones can influence the response to LPS, a polyclonal B cell activator. This may have implications for the sex differences seen in autoimmune diseases. PMID- 2307580 TI - Inhibition of interleukin 1 (IL-1)-elicited leukocytosis and LPS-induced fever by soluble immune response suppressor (SIRS). AB - IL-1-induced leukocytosis was inhibited or blocked in a dose-dependent manner by SIRS, an antigen-nonspecific suppressive lymphokine, when administered intravenously or per os to CBA mice. Timing experiments showed that SIRS effectively inhibited the leukocytosis when administered within 30 minutes of the IL-1. An antipyrogenic activity of SIRS was observed in rabbits injected intravenously with LPS. SIRS, given intravenously in one or two doses, markedly reduced LPS-induced fever. SIRS (2000 units) was a more effective antipyretic agent than aspirin (3 mg/kg body weight, intramuscularly). The results suggest that SIRS may be a potential drug for use in IL-1-mediated disorders. PMID- 2307581 TI - Elucidation of cellular targets responsible for tetrachlorodibenzo-p-dioxin (TCDD)-induced suppression of antibody responses: II. The role of the T lymphocyte. AB - Various immunological assays have been applied by our laboratory in an attempt to assess the role of the T-cell in the TCDD-induced suppression of the antibody response by murine B6C3F1 splenic lymphocytes. Animals were treated in vivo (via gavage) with 1.0 microgram/kg TCDD in corn oil for 5 days before in vitro analysis of splenocyte immunocompetence and T-cell function. To study the effects on T-helper cell function, alterations in the proliferative responses of T-cells following TCDD exposure were investigated. Results show no significant difference in [3H]thymidine uptake between vehicle- and TCDD-treated whole splenocytes 24 h after in vitro stimulation with the T-cell mitogen Con A. This is consistent with the finding that IL-2 production at either 24 or 48 h after Con A stimulation of TCDD-treated lymphocytes was not significantly different from that of vehicle treated controls. The possibility of the induction of a suppressor T-cell by TCDD was also investigated. Titration of T-cells from TCDD-treated mice into naive splenocyte cultures did not suppress the humoral response to either a T-dependent (SRBC) or a T-independent (DNP-Ficoll) antigen. In contrast, titration of cells stimulated in vitro with Con A for 48 h (a positive control for the induction of a suppressor T-cell) inhibited humoral responses of naive cells to both types of antigen. Likewise, T-cells plus macrophages from TCDD-treated mice did not suppress the in vitro humoral responsiveness of naive B-cells plus macrophages to a T-independent antigen (DNP-Ficoll). These results would indicate that an alteration in T-cell function following TCDD exposure does not play a role in the suppression of the antibody response elicited by antigen stimulation of murine B6C3F1 splenocytes. PMID- 2307582 TI - Radiopharmaceutical basis of nuclear medicine. Proceedings of a symposium. Farmington, Connecticut, U.S.A., 10-12 March 1989. PMID- 2307583 TI - Metabolic basis of nuclear medicine. PMID- 2307584 TI - All patients deserve respect as human beings. PMID- 2307585 TI - The human immunodeficiency virus (HIV) has been found to infect heart cell tissues. PMID- 2307586 TI - Correcting the misperceptions surrounding osteopathic medicine. PMID- 2307587 TI - Mandatory in-flight medical equipment earns high marks. PMID- 2307588 TI - Physician awareness of elevated cholesterol. AB - Recent studies suggest a heightened awareness of the association between elevated cholesterol and heart disease. Physician awareness of an elevated cholesterol level was investigated at a university-affiliated, 200-bed community hospital. All cholesterol levels greater than 240 mg/dL on a multichemistry profile were evaluated regarding physician awareness. Criteria for awareness included any notation in the patient's chart indicating the physician's recognition of the abnormal cholesterol level or therapeutic intervention (dietary or pharmacologic). During March 1986, an awareness level of 20% was found. A similar review in March 1988 revealed no change despite a redefinition of the normal laboratory range of serum cholesterol from 133 to 298 mg/dL to 130 to 240 mg/dL. On April 12, 1988, a 1-hour lecture sponsored by the Physician Cholesterol Education Program was presented at a hospital general staff meeting. Physician cholesterol awareness rose to 51.6% for the remainder of April through May 1988, and was 48.3% at 6-month post-CME follow-up. Chart reviews showed no heightened physician awareness related to the patient's age, sex, or diseases secondarily associated with increased cholesterol; however, increased physician awareness was associated with the primary diagnosis of atherosclerotic vascular disease and severity of hypercholesterolemia. Physician awareness of an elevated serum cholesterol level was poor during two retrospective prevalence surveys but improved considerably after delivery of an educational program. PMID- 2307589 TI - General practice residency training and the osteopathic profession: trends and issues for the 1990s. AB - With the 1989-1990 training year, the length of postinternship residency training in osteopathic general practice will increase from 1 to 2 years. The longer residency is expected to give trainees a more complete and more competitive education and to protect them against discrimination regarding hospital privileges. With this change comes the opportunity to evaluate the current status of residency training in the field and to use the data as the basis for making rational predictions and recommendations for the future of the specialty. The author considers the effect of curriculum changes on the operation of training residents in osteopathic general practice. He examines the structure of the new training program and discusses issues pertaining to osteopathic general practice. PMID- 2307591 TI - Television and teens: health implications. Los Angeles, California, June 22-24, 1988. Proceedings. PMID- 2307590 TI - Transient acantholytic dermatosis treated with isotretinoin. AB - Transient acantholytic dermatosis is a self-limiting benign disease. It is characterized by multiple pruritic erythematous papules and papulovesicles found predominantly on the trunk and extremities. This primary acantholytic dermatosis affects individuals older than 40 years. We present a case study of an individual who received a regimen of isotretinoin (Accutane) for treatment of severe pruritus after conventional forms of therapy failed to alleviate his condition and abate the formation of new lesions. PMID- 2307592 TI - Effects of televised alcohol messages on teenage drinking patterns. AB - This paper presents an overview of theoretical perspectives applicable to the effects of television drinking portrayals on adolescent audiences, focusing on the influence of beer and wine advertising and entertainment depictions of drinking behavior. A critical review of survey research evidence indicates that alcohol commercials contribute to a modest increase in overall consumption by teenagers and may have a slight impact on alcohol misuse and drunk driving. There are no studies measuring the effects of entertainment programming on adolescents, but content analyses suggest the potential for increased prodrinking attitudes and behaviors. Policy implications for addressing the deleterious effects of televised drinking are discussed, and priorities for future research are identified. PMID- 2307593 TI - Television and teens: health implications. Introduction. PMID- 2307594 TI - Study group report on the impact of televised drinking and alcohol advertising on youth. PMID- 2307595 TI - Study group report on the impact of television violence on adolescents. PMID- 2307596 TI - Study group report on the impact of television portrayals of gender roles on youth. PMID- 2307598 TI - Study group report on the impact of television on adolescent views of sexuality. PMID- 2307597 TI - Television and adolescent sexuality. AB - Existing studies of the sexual content of television programming and advertising and the effects of this content on adolescent viewers are reviewed. Content studies show that the frequency of sexual references have increased in the past decade and are increasingly explicit. Studies of the effects of this content, while scarce, suggest that adolescents who rely heavily on television for information about sexuality will have high standards of female beauty and will believe that premarital and extramarital intercourse with multiple partners is acceptable. They are unlikely to learn about the need for contraceptives as a form of protection against pregnancy or disease. Suggestions for future research and trends in television programming policies are explored. PMID- 2307599 TI - You are what you eat--what you eat is what you are. AB - Eating disorders among adolescents in the United States constitute the most frequent nutritional problems in this age group, and their prevalence appears to be increasing. A causal relationship of television viewing to obesity is strongly suggested for children and adolescents. Perhaps as much as 25% of the recent increase in obesity among adolescents may be attributable to increases in television viewing. Associations between television viewing and anorexia and bulimia are less explicit than they are for obesity. Nonetheless, because children and adolescents spend more time viewing television than they do in any activity other than sleep, the world shown on television may acquire a greater reality than the world that is experienced. The low frequency of obesity among televised characters, combined with the frequent food-related references that are contained in both commercials and programming, may promote unrealistic conclusions regarding eating and body weight. Television reflects a cultural contradiction by promoting food consumption and leanness. In this context, bulimia may be viewed as an adaptive response, because only bulimics can eat everything they wish and remain thin. PMID- 2307600 TI - Study group report on the impact of television on adolescent nutritional status. PMID- 2307601 TI - Television and teens: health implications. Executive summary. AB - Throughout the study group deliberations, there were issues that cross-cut all discussions and suggestions. While the focus of the conference was on television, it is not possible to talk about television without including advertising, cable, and independent stations as well as the networks. In addition, television cannot be discussed in isolation from movies, for with VCRs and television reruns, movies are an integral part of the television scene. A second theme that transcended most discussion was a reluctance to call upon external regulatory mechanisms to control what many see as the excesses of television. There was sensitivity and concern for striking a balance between safeguarding basic freedoms, on one hand, and assuring the health and well being of the nation on the other. In terms of specific recommendations, there were some key general agreements: 1. Need for Interdisciplinary Dialog. Repeatedly, concern was voiced on how little understanding there is among and between those who are primarily concerned with the health and development of young people and those who develop programs viewed by that population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307602 TI - TV and teens. PMID- 2307604 TI - More on "speciesism is the natural order". PMID- 2307603 TI - Ear trimming in dogs. PMID- 2307606 TI - National Pet Week commemorative resolution moves through Congress. PMID- 2307605 TI - Sulfonamides and blood dyscrasias. PMID- 2307607 TI - Animal rights and the veterinarian. PMID- 2307608 TI - The Congressional Science Fellowship: a first. PMID- 2307609 TI - Viewpoints on dairy herd fertility. PMID- 2307610 TI - ECG of the month. Heart rhythm disturbance after IV administration of anticholinergic drugs. PMID- 2307611 TI - Adverse effect of orally administered magnesium hydroxide on serum magnesium concentration and systemic acid-base balance in adult cattle. AB - Two cows, 1 with diarrhea and 1 with signs of forestomach outflow obstruction, were treated in part with repeated doses of a commercially available antacid/cathartic preparation containing magnesium hydroxide. Both cows subsequently were determined to have hypermagnesemia, along with severe metabolic alkalosis. In addition, each cow was comatose at the time of death. A clinical study was initiated to investigate the causal relationship between the ingestion of magnesium hydroxide and the generation of hypermagnesemia and metabolic alkalosis in adult cows. Twelve healthy mature cross bred beef cows were allotted at random to a fed or fasted (simulated anorexia) group, with 2 untreated and 4 treated cows in each group. A single dose of magnesium hydroxide (1.5 g/kg of body weight, suspended in 3.8 L of warm water) was administered per os to each treated cow, whereas each control cow was given only water. Individual determinations of selected venous blood gas values (plasma bicarbonate ion [HCO3 ] concentration, and base excess [BE]), serum magnesium (Mg) concentration, and urine magnesium fractional clearance ratio (Mg-FCR) were made immediately before drug administration, and at 2, 4, 8, 12, 24, and 36 hours after treatment. Compared with control values at the conclusion of the study, mean serum Mg concentration, urine Mg-FCR, plasma HCO3- concentration, and BE were significantly higher (P = 0.0001, P = 0.0015, P = 0.028, and P = 0.021, respectively) in treated cows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307612 TI - Prevalence of antithyroglobulin antibodies detected by enzyme-linked immunosorbent assay of canine serum. AB - Antithyroglobulin antibody (ATA) values were higher in dogs with low total serum thyroxine (T4) and triiodothyronine (T3) values than in dogs with T3 and T4 values within reference value limits. In the population studied, Doberman Pinschers were predisposed to the development of ATA; there was no sex predilection for development of ATA. Antithyroglobulin antibodies and thyroid status were evaluated in 2 groups of healthy dogs (n = 30) and in 470 canine serum samples submitted for T3 and T4 value determination. Antithyroglobulin antibodies were evaluated by ELISA, and thyroid status was evaluated by measurement of total serum T3 and T4 by radioimmunoassay. PMID- 2307613 TI - Effect of dietary iron content on hematologic and other measures of iron adequacy in dogs. AB - Eighteen 9- to 10-week old Beagles were fed casein-based diets (4,710 kcal of metabolizable energy/kg of body weight) containing either 12, 80, or 160 mg of iron/kg of diet. Growth and feed consumption were monitored throughout the 47-day study. Hematocrit (Hct), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), RBC numbers, erythrocyte protoporphyrin (EP) concentration, serum iron concentration, serum total iron-binding capacity (TIBC), and serum ferritin concentration were determined weekly. Growth rate and feed efficiency were not significantly influenced by dietary iron content. At 14 days, Hb concentration, Hct, MCV, MCH, RBC numbers, and serum iron concentration were significantly (P less than 0.05) lower in dogs fed the 12 mg/kg diet, and remained significantly low for the remainder of the study. Erythrocyte protoporphyrin concentration increased significantly (P less than 0.05) by 14 days in dogs fed the basal diet, and remained significantly high relative to that in dogs of the other dietary groups for the remainder of the study. Serum ferritin concentration decreased in dogs of the group fed the basal diet, with a significant (P less than 0.05) difference beyond day 42. Differences in Hct, MCH, MCV, or hemoglobin, serum iron, serum ferritin, or EP concentration were not found between groups fed 80 and 160 mg of iron/kg of diet. Liver nonheme iron content was significantly (P less than 0.05) affected by dietary iron content. PMID- 2307614 TI - Long-term survival after surgical excision of a schwannoma of the sixth cervical spinal nerve in a dog. AB - A schwannoma of the sixth cervical spinal nerve in a 5-year-old Shetland Sheepdog was surgically excised, sparing the thoracic limb and resulting in long-term survival. The dog had been referred because of slowly progressive left thoracic limb lameness. The lesion was localized to the left suprascapular and musculocutaneous nerves or the C6 and C7 spinal nerves on the basis of neurologic examination, electrodiagnostic examination, and myelography. Surgical exploration revealed a mass, which was excised and identified histologically as a schwannoma. Three and a half years later, the dog was normal except for mild gait abnormality, focal muscle atrophy, and a focal area of decreased cutaneous sensation of the left thoracic limb. PMID- 2307615 TI - Cutaneous mucinous vesiculation in a dog with hypothyroidism. AB - Hypothyroidism was documented in an overweight dog with bilateral entropion, blepharoptosis, and multiple, non-inflammatory papular and vesicular lesions on the head. Histologic evaluation of skin biopsy specimens confirmed the diagnosis of mucinous vesiculation. All skin and eyelid abnormalities resolved in response to thyroid hormone supplementation. PMID- 2307616 TI - Megaesophagus in two cats. AB - Megaesophagus was diagnosed in 2 cats. Both had a history of regurgitation, and one was dyspneic. Radiography of the thorax and abdomen revealed generalized megaesophagus and gastric distention with gas. There was no esophageal motility during fluoroscopic observation. The prognosis for cats with megaesophagus is guarded. Although they may be satisfactory pets, cats with this condition should not be used for breeding because the condition is believed to be inherited through recessive genes. PMID- 2307617 TI - Third-degree perineal lacerations and rectovestibular fistulae in cattle: 20 cases (1981-1988). AB - The case records of 20 cows with either a third-degree perineal laceration or rectovestibular fistula were reviewed to ascertain the signalment, history, treatment, and long-term result of treatment. Fifteen cows, including 10 first calf cows, had third-degree perineal lacerations that occurred at calving. Surgery was done in 14 of 15 cows; 10 of the 14 (71%) remained fertile. The cow that was not treated surgically was culled after 24 months because of infertility. Five cows had a rectovestibular fistula; 4 of these were treated surgically. The cow that did not have surgery healed by second intention and remained fertile, and 3 of the 4 cows in which surgery was performed were fertile. None of the cows that produced calves after the initial injury suffered a perineal laceration at subsequent calvings. Single-stage surgical repair of third-degree perineal laceration or rectovestibular fistula appeared to have a good prognosis for subsequent fertility in cows. PMID- 2307618 TI - What is your diagnosis? Swelling of spinal cord associated with dural tear between segments T13 and L1. PMID- 2307619 TI - American Society of Andrology. 15th annual meeting. Program and abstracts. April 6-9, 1990, Columbia, South Carolina. PMID- 2307620 TI - FR109615, a new antifungal antibiotic from Streptomyces setonii. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity. AB - FR109615, a new antibiotic active against Candida, was isolated from Streptomyces setonii No. 7562. Based on the spectroscopic data, the structure of FR109615 was elucidated as cis-2-aminocyclopentane-1-carboxylic acid (1). The compound showed the excellent in vivo efficacy in a generalized infection test of mice. PMID- 2307621 TI - Two novel phenolics from Actinomadura verrucosospora. PMID- 2307622 TI - Isolation and structures of mono- and di-deacetyl chromomycin antibiotics 02-3D and 02-3G from Streptomyces avellaneus. PMID- 2307623 TI - Synthesis and beta-lactamase inhibitory activity of 7 alpha-hydroxyethyl cephem sulfone and sulfoxide derivatives. PMID- 2307624 TI - Isolation and structure of phosphazomycin C. PMID- 2307625 TI - Cyclic acetal derivatives of mitomycin C. PMID- 2307626 TI - Water soluble derivatives of rebeccamycin. PMID- 2307627 TI - New biosynthetic anthracyclines related to barminomycins incorporating barbiturates in their moiety. AB - Three new anthracyclines, FCE 21424 (2), FCE 24366 (3) and FCE 24367 (4), were isolated from culture broths of Streptomyces peucetius and its mutant strains after addition of sodium barbiturates during the fermentation. Structural assignment, achieved through spectroscopic and degradative studies, that the new anthracyclines had a common barminomycin-like structure incorporating different barbiturate moieties. The new anthracyclines were found to display outstanding cytotoxicity and remarkable potency "in vivo" against P388 ascitic leukemia. PMID- 2307629 TI - Studies on new dehydropeptidase inhibitors. II. Structural elucidation and synthesis of WS1358A1 and B1. AB - The structures of WS1358A1 and B1, new dehydropeptidase inhibitors isolated from Streptomyces parvulus subsp. tochigiensis No. 1358, have been established to be 2 hydroxy-2-hydroxyaminocarbonyl-3-methylglutaric acid (1) and 2-hydroxy-2 hydroxyaminocarbonylglutaric acid (2), respectively, on the basis of spectroscopic evidence and synthesis of the racemates. PMID- 2307628 TI - Studies on new dehydropeptidase inhibitors. I. Taxonomy, fermentation, isolation and physico-chemical properties. AB - WS1358A1 (FR104007) and B1 (FR104008), new potent inhibitors of renal dehydropeptidase, were isolated from the culture broth of strain No. 1358 which was identified as Streptomyces parvulus subsp. In vitro inhibitory activities (IC50 value) of WS1358A1 and B1 against porcine renal DHP were 3 and 600 nM, respectively. PMID- 2307630 TI - The absolute configuration of decilonitrose, a sugar component of decilorubicin, is undoubtedly 2,3,6-trideoxy-3-C-methyl-3-nitro-L-ribo-hexopyranose. AB - The absolute structure of decilonitrose, a sugar component of an antitumor antibiotic decilorubicin was decided to be 2,3,6-trideoxy-3-C-methyl-3-nitro-L ribo-hexopyranose by synthesis of its methyl beta-glycoside starting from L rhamnose through the 3-ulose. In the synthetic route, any configurational ambiguities do not exist. PMID- 2307631 TI - 6-(substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase. I. Racemic 6-ethylidenepenems. AB - The dehydration of various 6-(1-hydroxyethyl)penems to give E- and Z-6 ethylidenepenems is described. Both isomers have been shown to be potent broad spectrum inhibitors of bacterial beta-lactamases capable of reducing the MIC values of beta-lactam antibiotics such as amoxycillin and cephaloridine against a wide range of resistant organisms. PMID- 2307632 TI - Site of regulation of nanaomycin biosynthesis by inorganic phosphate. AB - The site of regulation of nanaomycin biosynthesis by inorganic phosphate was studied with washed cells previously grown in a chemically defined medium containing a high- or low-phosphate concentration. The former mycelia produced only about one-tenth the amount of nanaomycin A from acetate as did the latter mycelia. On the other hand, the bioconversions of nanaomycin D to A and nanaomycin A to E were only slightly affected. It is suggested that the site of regulation of nanaomycin biosynthesis by inorganic phosphate lies within steps between acetate and nanaomycin D. PMID- 2307633 TI - An examination of age and cognitive test performance across job complexity and occupational types. AB - In this study, job complexity and occupational type were examined as potential moderators of the relationship between age and cognitive ability. Data included general, verbal, and numerical ability scores for 21,646 individuals in the General Aptitude Test Battery (GATB) data base. These individuals comprised 102 unique samples and 10 major occupational groups. Differences in the relationship between age and cognitive ability test scores were observed across occupational types but not for different levels of job complexity. Findings were discussed in terms of a need for research that examines specific life and work experiences and how such experiences may influence an individual's cognitive abilities across the life span. PMID- 2307634 TI - Occupational attainment as a function of abilities and interests: a longitudinal analysis using project TALENT data. AB - Ability, interest, gender, and family socioeconomic status of 13,248 tenth-grade participants in Project TALENT were studied as they relate to occupational attainment by using discriminant analysis. Individuals were classified into 12 broad categories reported 11 years after graduation. Accuracy analyses indicated correct classifications significantly above chance for all except the Technical and Sales categories. Within-category classification percentages were higher for all groups except Construction. Five canonical discriminant functions that jointly accounted for 96.8% of the between-groups variance were interpreted. The first 2 accounted for 81.9% of the variance. Function 1 was a general ability function; Function 2 differentiated the categories on the basis of mathematics ability and gender. Functions 3 through 5 accounted for 14.9% of the between groups variance. Some implications of these findings are discussed. PMID- 2307635 TI - Marked sex differences on a fine motor skill task disappear when finger size is used as covariate. AB - Purdue Pegboard performance of 16 male and 25 female right-handed college students were compared, and results were replicated with 25 male and 28 female subjects. In agreement with the literature, women performed significantly better than men. When measures of index finger and thumb thickness were used as covariate, all significant sex differences in performance disappeared. Negative correlations between performance and finger size were observed in both sexes. Sex differences in fine manual dexterity tasks may therefore be confounded by sex differences in finger size. PMID- 2307636 TI - In the interest of clearer communication. PMID- 2307638 TI - Cell proliferation on hydrogels. AB - The adhesion and proliferation of mammalian fibroblasts (Flow 7000) on the surface of hydrophilic (copolymer of N-vinyl-2-pyrrolidone and methyl methacrylate) and hydrophobic [polymethylmethacrylate (PMMA) stereocomplex] hydrogels with a wide range in water content were studied morphologically and quantitatively. It was demonstrated that cell proliferation on hydrogels by a static culture method decreased as the water content of the gels increased. However, it is remarkable that the cell proliferation on PMMA hydrogels with a high water content is equivalent to that on glass Petri dishes. The results obtained in the proliferation of cells on the surface of these hydrogels closely correspond to the state of cell adhesion. When fresh medium or air was perfused from the opposite side of the PMMA hydrogel membrane on which the cells were proliferating (perfusion method), the cells continued to grow into a higher density than with the conventional static culture method. In the case of fresh medium perfusion, the amount of proliferated cell was dependent on both the permeability of the membrane and the density of the membrane "scaffolding." Virus multiplication in the cultured cells increased in proportion to the cell density, whereas the cell function was similar in both culture methods. PMID- 2307637 TI - Effect of vitamin E on 2-deoxy-D-glucose uptake in human fibroblast cultures. AB - 2-Deoxy-D-glucose (2-DOG) uptake was tested in human fibroblast cultures in the presence and absence of vitamin E. Addition of 10 micrograms/ml vitamin E to the culture medium significantly reduced this uptake for 2-DOG concentrations of 0.005 to 10 mmol/liter (P less than or equal to 0.01). The decrease of 2-DOG uptake was inversely proportional to the rise in 2-DOG concentration (P less than or equal to 0.01). The presence of vitamin E reduced by 71% the average cellular level of lipid peroxides (expressed as thiobarbituric acid reactive substances) and caused a small but significant decrease in the cholesterol concentration (P less than or equal to 0.01). These last results might explain the decrease in 2 DOG uptake observed in the presence of vitamin E. PMID- 2307639 TI - Cell-mediated contraction of collagen lattices in serum-free medium: effect of serum and nonserum factors. AB - This study was conducted to identify a defined, serum-free culture medium that supports cell dependent contraction of a collagen lattice. Collagen lattices were found to contract in cultures containing human foreskin fibroblasts (HFF) or rabbit aortic smooth muscle (RASM) cells incubated in serum-free medium. HFF and RASM cells required different supplements to contract the collagen gels. HFF cultured in Dulbecco's modified Eagle's (DME) medium supplemented with bovine serum albumin (BSA) and either endothelial cell growth supplement (EnGS), insulin (In), or platelet derived growth factor (PDGF) supported collagen lattice contraction. Replacement of BSA with casein without the addition of other supplements improved contraction. In contrast, RASM cells supplemented with BSA, EnGS, In, and PDGF were able to contract collagen gels only minimally. Similar to HFF, RASM cells cultured in DME medium supplemented with casein, but without the addition of other supplements, contracted collagen lattices. HFF-mediated collagen contraction was inhibited by prostaglandins E1 or E2, fibronectin, or ascorbic acid. The reported serum-free model provides a useful in vitro method to investigate the role of serum and nonserum factors regulating cell mediated contraction of insoluble collagen fibrils. PMID- 2307640 TI - Immortal clones of NM1 keratinocytes contain an isochromosome of the long arm of chromosome 8. PMID- 2307641 TI - Rat primary hepatocyte cultures are a good model for examining metallothionein induced tolerance to cadmium toxicity. AB - The effect of Zn-induced metallothionein (MT) on the toxicity, uptake, and subcellular distribution of cadmium (Cd) was examined in rat primary hepatocyte cultures and compared to results obtained earlier in this laboratory from intact animals. Hepatocytes were isolated and grown in monolayer culture for 22 h and subsequently treated with ZnCl2 (100 microM) for 24 h, which increased MT concentration about 15-fold. After Zn pretreatment, hepatocytes were exposed to Cd for 24 h. Cytotoxicity was assessed by enzyme leakage, intracellular potassium loss, and cellular glutathione content. The toxicity of Cd was much less in Zn pretreated cells than in control cells, similar to that previously demonstrated in the intact animal. Zn pretreatment had no appreciable effect on the hepatocellular uptake of 109Cd, but markedly altered its subcellular distribution, with more Cd accumulating in the cytosol and less in the nuclear, mitochondrial, and microsomal fractions. In the cytosol of Zn-pretreated cells, Cd was associated mainly with MT; in contrast, cytosolic Cd in control cells was mainly associated with non-MT macromolecules. Zn-induced changes in the subcellular distribution of Cd in vitro are identical to those observed in vivo in Zn-pretreated rats challenged with Cd. In summary, Zn pretreatment of rat primary hepatocyte cultures protects cells against Cd toxicity. Protection seems to be due to MT-promoted sequestration of Cd and reduction of the amount of Cd associated with critical organelles and proteins. These observations are similar to those noted in the whole animal. These results indicate that cultured hepatocytes are an ideal model for examining MT-induced tolerance to Cd hepatotoxicity. PMID- 2307643 TI - Terminology associated with cell, tissue, and organ culture, molecular biology, and molecular genetics. Tissue Culture Association Terminology Committee. PMID- 2307642 TI - Microbiological cultivation of Mycoplasma hyorhinis from cell cultures. AB - The failure of many cell culture isolates of Mycoplasma hyorhinis to grow on microbiological media has stressed the need for alternate assays to detect these organisms. The use of freshly prepared yeast extract in mycoplasmal media together with incubation in 5% CO2/air successfully detected M. hyorhinis in 12 of 12 infected cultures. These were not detected by the use of conventional mycoplasmal media using aerobic or anaerobic incubation. This assay may also be helpful in detection of other mycoplasmal species commonly isolated from cell cultures. PMID- 2307644 TI - Sinusitis and asthma. PMID- 2307645 TI - Effect of verapamil inhalation on bronchial asthma. AB - The effect of inhaled verapamil 20 mg on pulmonary functions and arterial blood gases in 15 patients with extrinsic bronchial asthma was studied in single-blind fashion. A significant decrease (p less than 0.05) in airway resistance and a significant increase (p less than 0.01) in specific conductance was observed after verapamil inhalation. A small increase (p less than 0.1) was observed in forced vital capacity and peak expiratory flow rate after verapamil inhalation; however, this was not statistically significant. None of the parameters of pulmonary function tests showed a significant change after normal saline inhalation. A significant fall in PaO2 (p less than 0.05) and PaCO2 (p less than 0.05) was noted after normal saline inhalation. PaCO2 showed a significant fall (p less than 0.01) after verapamil inhalation. Alveolar arterial oxygen gradient P(A-a)O2 widened significantly (p less than 0.001) after normal saline inhalation. A larger dose (20 mg) of verapamil inhalation produces a significant bronchodilator effect on large airways, but does not produce a significant change in arterial oxygen tension from the baseline value in patients with bronchial asthma. PMID- 2307646 TI - Description of a delivery method for continuously aerosolized albuterol in status asthmaticus. AB - The use of continuously nebulized beta agonists may be considered in the treatment of status asthmaticus, particularly when conventional therapy is failing. Methods of administration of continuously nebulized beta agonists may be cumbersome. We describe a delivery method which allowed simplification of this process, yielded accurate delivery of a specified dose of albuterol, and was beneficial in a reported case of status asthmaticus. PMID- 2307648 TI - Outer membrane polysaccharide deficiency in two nongliding mutants of Cytophaga johnsonae. AB - Phenol-extractable polysaccharides firmly associated with the outer membrane of the gliding bacterium Cytophaga johnsonae could be resolved by gel filtration in sodium dodecyl sulfate (SDS) or by SDS-polyacrylamide gel electrophoresis into a high-molecular-weight (H) fraction (excluded by Sephadex G-200) and a low molecular-weight (L) fraction. Fraction L was rich in components typical of lipid A and the core region of lipopolysaccharide (P, 3-hydroxy fatty acids, and 2-keto 3-deoxyoctonate) and evidently was a lipopolysaccharide with a limited number of distal, repeating polysaccharide units, as judged by SDS-polyacrylamide gel electrophoresis. In relation to total carbohydrate, the H fraction was rich in amino sugar but poor in (possibly devoid of) the lipid A and core components. Two nongliding mutants were highly deficient in the H fraction; one of these was deficient in sulfonolipid but could be cured by provision of a specific sulfonolipid precursor, a process that also resulted in the return of both the H fraction and gliding, as well as the ability to move polystyrene latex spheres over the cell surface. Hence, the polysaccharide may be the component that is directly involved in motility, and the presence of sulfonolipids in the outer membrane is necessary for the synthesis or accumulation of the polysaccharide. This conclusion was reinforced by the fact that the second nongliding, polysaccharide-deficient mutant had a normal sulfonolipid content. PMID- 2307647 TI - virG, an Agrobacterium tumefaciens transcriptional activator, initiates translation at a UUG codon and is a sequence-specific DNA-binding protein. AB - The Agrobacterium tumefaciens Ti plasmid virG locus, in conjunction with virA and acetosyringone, activates transcription of the virulence (vir) genes. Insertional and deoxyoligonucleotide-directed mutagenesis studies showed that both octopine and nopaline Ti plasmid virG genes initiate translation at a UUG codon. VirG protein initiated at this UUG codon was found to be 241 amino acid residues in length and had an apparent molecular mass of 27.1 kilodaltons. A Salmonella typhimurium trp-virG transcriptional fusion was constructed to overproduce VirG. Agrobacterium cells containing this gene fusion showed a large increase in virG activity in the presence of virA and acetosyringone. Since the trp promoter is not under virA-virG control, this result indicates that modification of VirG is necessary for its full activity. VirG overproduced in Escherichia coli was purified from inclusion bodies. It was found to be a DNA-binding protein that preferentially bound DNA fragments containing the 5' nontranscribed regions of the virA, -B, -C, -D, and -G operons. Significant specific binding to the 5' nontranscribed region sequences of virE was not detected. DNase I footprinting of the upstream regions of virC-virD and virG showed that VirG binds to sequences around the vir box region. PMID- 2307649 TI - Protein content and enzyme activities in methanol- and acetate-grown Methanosarcina thermophila. AB - The cell extract protein content of acetate- and methanol-grown Methanosarcina thermophila TM-1 was examined by two-dimensional polyacrylamide gel electrophoresis. More than 100 mutually exclusive spots were present in acetate- and methanol-grown cells. Spots corresponding to acetate kinase, phosphotransacetylase, and the five subunits of the carbon monoxide dehydrogenase complex were identified in acetate-grown cells. Activities of formylmethanofuran dehydrogenase, formylmethanofuran:tetrahydromethanopterin formyltransferase, 5,10 methenyltetrahydromethanopterin cyclohydrolase, methylene tetrahydromethanopterin:coenzyme F420 oxidoreductase, formate dehydrogenase, and carbonic anhydrase were examined in acetate- and methanol-grown Methanosarcina thermophila. Levels of formyltransferase in either acetate- or methanol-grown Methanosarcina thermophila were approximately half the levels detected in H2-CO2 grown Methanobacterium thermoautotrophicum. All other enzyme activities were significantly lower in acetate- and methanol-grown Methanosarcina thermophila. PMID- 2307650 TI - Conserved structures of cell wall protein genes among protein-producing Bacillus brevis strains. AB - Bacillus brevis HPD31 contains a surface (S)-layer protein, termed the HWP, which forms a hexagonal array in the cell wall. The 5' region of the HWP gene was isolated from a DNA library constructed in bacteriophage vector EMBL3 from a partial BamHI digest of the chromosomal DNA. The 3' region contained in a 2.7 kilobase BglII fragment of the DNA was cloned into Escherichia coli, using pUC118 as a vector. On the basis of the chemically determined N-terminal amino acid sequence, the HWP gene was found to encode a polypeptide consisting of 1,087 amino acid residues with a signal peptide of 53 or 23 amino acid residues. The deduced amino acid composition was similar to the chemical amino acid compositions of other S-layer proteins in the predominance of acidic relative to basic amino acids and in the very low content of sulfur-containing amino acids. The deduced amino acid sequence showed high homology (78%) with that of the middle wall protein of B. brevis 47. Furthermore, the multiple 5' ends of the HWP gene transcripts detected on S1 nuclease analysis closely resembled those of the middle wall protein gene transcripts. This complex structure was also conserved (greater than 85%) in the regulatory regions of two other cell wall protein genes isolated from B. brevis HPD52 and HP033, suggesting that the synthesis of the cell wall proteins is intricately regulated through a similar mechanism in protein-producing B. brevis. PMID- 2307651 TI - Specific inhibition of antenna bacteriochlorophyll synthesis in Chlorobium vibrioforme by anesthetic gases. AB - The green sulfur bacterium Chlorobium vibrioforme contains two types of bacteriochlorophyll (Bchl). The minor pigment, Bchl a, is associated primarily with the cell membrane and its reaction centers; and the major light-harvesting antenna pigment, Bchl d, is found primarily in the chlorosomes, which are attached to the inner surface of the cell membrane. Anesthetic gases, such as N2O, ethylene, and acetylene, were found to inhibit the synthesis of Bchl d, but not of Bchl a, thus allowing the cells to grow at high light intensities with a greatly diminished content of antenna pigment. Chlorosomes were absent or sparse in inhibited cells. Porphyrins accumulated in the inhibited cells. The major one was identified as the Bchl precursor magnesium-protoporphyrin IX monomethyl ester (Mg-PPME) by comparative absorption and fluorescence spectroscopy and thin-layer chromatography of the porphyrin and its derivatives with those of authentic protoporphyrin IX. Small amounts of Mg-PPME were present in control cells, but the addition of inhibitor caused a rapid increase in the Mg-PPME concentration, accompanying the inhibition of Bchl d synthesis. Cells grown in the presence of ethephon (as a source of ethylene) and allowed to stand in dim light for long periods accumulated large amounts of PPME and other porphyrins and excreted or released porphyrins, which accumulated as a brown precipitate in the culture. Inhibition of Bchl d synthesis was relieved upon removal of the inhibitor. These results suggest that the gases act at a step in pigment biosynthesis that affects the utilization of Mg-PPME for isocyclic ring formation. Synthesis of Bchl d and Bchl a may be differentially affected by the gases because of compartmentation of their biosynthetic apparatus or because competition for precursors favors Bchl a synthesis. An ethephon-resistant mutant strain was isolated by selection for growth in dim, long-wavelength light. The mutant cells were also resistant to acetylene, but not to N2O. The ability to reversibly generate viable Chlorobium cells that lack antenna pigments may be useful in photosynthesis research. The ethephon- and acetylene-resistant strain may be useful in the study of the enzymes and genes that are involved in the biosynthetic step that the gases affect. PMID- 2307652 TI - Symbiotic pseudorevertants of Rhizobium meliloti ndv mutants. AB - Nodule development (ndv) mutants of Rhizobium meliloti cannot invade alfalfa to establish a nitrogen-fixing symbiosis and instead induce the formation of small, white, unoccupied nodules on alfalfa roots. Such mutants also fail to produce the unusual cyclic oligosaccharide beta-(1----2)-glucan and show defects in several aspects of vegetative growth and function. Here we show that ndv mutants are severely reduced, although not totally deficient, in the ability to attach to and initiate infection threads on alfalfa seedlings, and we demonstrate that the symbiotic deficiency can be separated from the rest of the mutant phenotype by isolating second-site pseudorevertants. Pseudorevertants selected for restoration of motility, a vegetative property, regained a substantial amount of attachment capability but only slight infection thread initiation and symbiotic ability. Such strains also regained partial tolerance to growth at low osmolarity, even though they did not recover the ability to synthesize periplasmic beta-(1----2) glucan. Pseudorevertants selected on alfalfa for restoration of symbiosis were unrestored for beta-(1----2)-glucan production or any other vegetative property and regained little or no attachment or infection thread initiation capability. We take these data to indicate that wild-type R. meliloti normally has considerable excess capability for both attachment and infection thread initiation and that the symbiotic block in ndv mutants lies further along the developmental pathway than either of these processes, probably at the level of infection thread extension. Further, the fact that neither type of pseudorevertant recovered the ability to produce periplasmic beta-(1----2)-glucan raises the possibility that this oligosaccharide is not directly required for nodule development. PMID- 2307653 TI - Permeability barrier to hydrophilic solutes in Mycobacterium chelonei. AB - In order to define the permeability barrier to hydrophilic molecules in mycobacteria, we used as a model a smooth, beta-lactamase-producing strain of Mycobacterium chelonei. The rates of hydrolysis of eight cephalosporins by intact and sonicated cells were measured, and the permeability coefficient (P) was calculated from these rates by the method of Zimmermann and Rosselet (W. Zimmermann and A. Rosselet, Antimicrob. Agents Chemother. 12:368-372, 1977). P ranged from (0.9 +/- 0.3) x 10(-8) (benzothienylcephalosporin) to (10 +/- 3.3) x 10(-8) cm/s (cephaloridine); i.e., the P values were lower than those reported for Pseudomonas aeruginosa and Escherichia coli by 1 and 3 orders of magnitude, respectively. The permeability barrier was shown to reduce drastically the stream of drug molecules entering the cell, allowing the rather low level of beta lactamase (0.1 U/mg of protein with penicillin G) to decrease radically the concentration of the drug at the target; this explains the poor in vitro activities of the beta-lactams against M. chelonei. We also estimated P for small, hydrophilic molecules (glucose, glycerol, glycine, leucine), by studying their uptake kinetics. The values found, ranging from 15 x 10(-8) to 490 x 10(-8) cm/s, were consistent again with a very low permeability of M. chelonei cell wall. The permeation of cephalosporins was not very dependent on the hydrophobicity of the molecules or on the temperature, suggesting a hydrophilic pathway of penetration for these molecules. PMID- 2307654 TI - Generation of a membrane potential by sodium-dependent succinate efflux in Selenomonas ruminantium. AB - When Selenomonas ruminantium HD4 was grown in a chemostat, maximal succinate production and the highest molar growth yield values were both observed at a dilution rate of roughly 0.2 h-1. To determine the possible relationship between succinate efflux and high molar growth yields, the generation of a membrane potential by succinate efflux was studied in whole cells and vesicles (inside-out and right-side-out) prepared from S. ruminantium. Washed whole cells took up succinate in the absence of an exogenous energy supply; uptake was completely abolished by brief treatment with dinitrophenol or with nigericin and valinomycin. High levels of sodium ions (with respect to the intracellular sodium concentration in the assay buffer had a stimulatory effect on succinate uptake. When succinate was added to inside-out vesicles, a membrane potential (inside positive) was generated, as indicated by fluorescence quenching of the anionic lipophilic dye Oxonol V. Fluorescence quenching was sensitive to uncoupling by gramicidin D but only partially sensitive to the uncoupler carbonyl cyanide-p trifluoromethoxyphenylhydrazone. In right-side-out vesicles, succinate uptake could be driven by an artificially imposed sodium gradient but not by a potassium diffusion potential; imposition of both a sodium gradient and potassium diffusion potential resulted in improved succinate uptake. The generation of a membrane potential (inside negative) upon succinate efflux was demonstrated directly in right-side-out vesicles when succinate-loaded vesicles were diluted into succinate-free buffer, and the lipophilic cationic probe tetraphenylphosphonium accumulated in the vesicles. Results indicate that an electrogenic succinate sodium symporter is present in S. ruminantium. Transport of succinate out of the cell via the symporter might be responsible for the high molar growth yields obtained by this organism when it is grown at dilution rates where maximal succinate production occurs. PMID- 2307655 TI - Attachment of the adhesive holdfast organelle to the cellular stalk of Caulobacter crescentus. AB - Caulobacters attach to surfaces in the environment via their holdfasts, attachment organelles located at the base of the flagellum in swarmer cells and later at the end of the cellular stalk in the stalked cells which develop from the swarmer cells. There seems to be little specificity with respect to the types of surfaces to which holdfasts adhere. A notable exception is that the holdfast of one cell does not adhere to the cell surface of another caulobacter, except by joining holdfasts, typically forming "rosettes" of stalked cells. Thus, the localized adhesion of the holdfasts to the cells is in some way a specialized attachment. We investigated this holdfast-cell attachment by developing an adhesion screening assay and analyzing several mutants of Caulobacter crescentus CB2A selected to be defective in adhesion. One class of mutants made a normal holdfast by all available criteria, yet the attachment to the cell was very weak, such that the holdfast was readily shed. Another class of mutants made no holdfast at all, but when mixed with a wild-type strain, a mutant of this class participated in rosette formation. The mutant could also attach to the discarded holdfast produced by a shedding mutant. In addition, when rosettes composed of holdfast-defective and wild-type cells were examined, an increase in the number of holdfast-defective cells was correlated with a decrease in the ability of the holdfast material at the center of the rosette to bind colloidal gold particles. Gold particles are one type of surface to which holdfasts adhere well, suggesting that the stalk end and the colloidal gold particles occupy the same sites on the holdfast substance. Taken together, the data support the interpretation that there is a specialized attachment site for the holdfast at the base of the flagellum which later becomes the end of the stalk, but not a specialized region of the holdfast for attachment to this site. Also, attachment to the cell is accomplished by bond formations that occur not only at the time of holdfast production. Thus, we propose that the attachment of the holdfast to the cell is a true adhesion process and that the stalk tip and base of the flagellum must have compositions distinctly different from that of the remainder of the caulobacter cell surface. PMID- 2307656 TI - Characterization of superoxide dismutases purified from either anaerobically maintained or aerated Bacteroides gingivalis. AB - Superoxide dismutases (SODs) were purified from extracts of either anaerobically maintained or aerated Bacteroides gingivalis. Each purified enzyme (molecular weight, 46,000) was a dimer composed of two subunits of equal sizes. SOD from anaerobically maintained cells (anaero-SOD) contained 1.79 g-atom of Fe and 0.28 g-atom of Mn, and SOD from aerated cells (aero-SOD) contained 1.08 g-atom of Mn and 0.36 g-atom of Fe. Spectral analysis showed that anaero-SOD had the characteristic of Fe-SOD and that aero-SOD had that of Mn-SOD. Both enzyme preparations contained three isozymes with identical isoelectric points. On the basis of inactivation of SOD by H2O2, it was found that aero-SOD consisted of one Mn-SOD and a small quantity of two Fe-SODs, whereas anaero-SOD contained only Fe SOD. However, each apoprotein from anaero-SOD and aero-SOD, prepared by dialysis in guanidinium chloride plus 8-hydroxyquinoline, showed only one protein band each with the same isoelectric point on an isoelectric focusing gel. Subsequent dialysis of both apoenzymes with either MnCl2 or Fe(NH4)2(SO4)2 restored the activity. These reconstituted SODs showed only one protein band with SOD activity on native polyacrylamide gel electrophoresis. Furthermore, the two enzymes had similar amino acid compositions, and their amino-terminal sequences were identical through the first 12 amino acids. These results suggest that the three isozymes of anaero-SOD and aero-SOD in B. gingivalis are formed from a single apoprotein. PMID- 2307657 TI - Chloride transport pathways and their bioenergetic implications in the obligate acidophile Bacillus coagulans. AB - The protonophore-mediated collapse of the large delta pH that acidophiles maintain across their cytoplasmic membranes was augmented by the presence of Cl-, and Cl- influx into the cells occurred evidently in response to the protonophore induced increase in the inside-positive membrane potential (+ delta psi). In respiring cells, the addition of Cl- but not SO4(2-) salts caused a rapid and precipitous decrease in the + delta psi. A Nernstian relationship between the imposed transmembrane K+ gradient and the valinomycin-induced K+ diffusion potentials was observed when everted membrane vesicles were loaded with K2SO4 or KH2PO4 but not when loaded with KCl or KNO3. Thus, electrogenic Cl- transport occurred in Bacillus coagulans. In addition, a nonelectrogenic temperature sensitive Cl- transport mechanism, with the net Cl- efflux coefficient (PCl-) ranging from 1.5 x 10(-4) to 6.1 x 10(-6) cm/s, accounted for the massive Cl- efflux from Cl(-)-loaded cells. Thus, B. coagulans, despite its dependence on the + delta psi and therefore the need to exclude anions, apparently possesses specific mechanisms for Cl- permeation. Active cells of B. coagulans prevented Cl accumulation from attaining an electrochemical equilibrium, maintaining a delta micro Cl- of ca. -63 mV. B. coagulans therefore also possesses an energy dependent mechanism for Cl- exclusion from the cells. PMID- 2307658 TI - Genetic analysis of the yopE region of Yersinia spp.: identification of a novel conserved locus, yerA, regulating yopE expression. AB - The yopE gene of Yersinia pseudotuberculosis was recently sequenced, and YopE was identified as an indispensable virulence determinant when tested in a mouse model (A. Forsberg and H. Wolf-Watz, Mol. Microbiol. 2:121-133, 1988). In the study described here, the DNA sequences of the yopE genes of Yersinia pestis EV76 and Yersinia enterocolitica 8081 were determined and compared with that of the Y. pseudotuberculosis gene. Only two codons were found to differ, both leading to amino acid replacements, when the gene from Y. pestis was compared. These two replacements were also present in the gene from Y. enterocolitica; in addition, 18 other codons were found to differ. Thirteen of these substitutions led to amino acid replacements. Downstream of the yopE gene, the plasmid partition locus par was found to be conserved in all three species. In Y. enterocolitica 8081, the sequence homology was interrupted by a putative insertion sequence element inserted between the yopE gene and the par region at a position only 5 base pairs downstream of the yopE stop codon. Upstream of the yopE gene, 620 base pairs were conserved in the three species. This region contained a 130-amino-acid-long open reading frame reading in the opposite direction to the yopE gene and expressed a 14-kilodalton protein in minicells. An insertion mutation in this region constructed in Y. pseudotuberculosis expressed significantly lower amounts of YopE protein in vitro than did the corresponding wild type. The expression level could be restored by transcomplementation. This new locus was designated yerA, for yopE-regulating gene A. The yerA mutant was avirulent when mice were challenged by oral infection. PMID- 2307659 TI - Molecular cloning, expression, and characterization of endo-beta-1,4-glucanase genes from Bacillus polymyxa and Bacillus circulans. AB - Endo-beta-1,4-glucanase genes from Bacillus circulans and from B. polymyxa were cloned by direct expression by using bacteriophage M13mp9 as the vector. The enzymatic activity of the gene products was detected by using either the Congo red assay or hydroxyethyl cellulose dyed with Ostazin Brilliant Red H-3B. The B. circulans and B. subtilis PAP115 endo-beta-1,4-glucanase genes were shown to be homologous by the use of restriction endonuclease site mapping, DNA-DNA hybridization, S1 nuclease digestion after heteroduplex formation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the protein products. Analysis of the nucleotide sequence of 3.1 kilobase pairs of cloned B. polymyxa DNA revealed two convergently transcribed open reading frames (ORFs) consisting of 398 codons (endoglucanase) and 187 codons (ORF2) and separated by 374 nucleotides. The coding region of the B. polymyxa endoglucanase gene would theoretically produce a 44-kilodalton preprotein. Expression of the B. polymyxa endoglucanase in Escherichia coli was due to a fusion of the endoglucanase gene at codon 30 with codon 9 of the lacZ alpha-peptide gene. The B. polymyxa endoglucanase has 34% amino acid similarity to the Clostridium thermocellum celB endoglucanase sequence but very little similarity to endoglucanases from other Bacillus species. ORF2 has 28% amino acid similarity to the NH2-terminal half of the E. coli lac repressor protein, which is responsible for DNA binding. PMID- 2307660 TI - Identification and characterization of plasmids from the western aster yellows mycoplasmalike organism. AB - Supercoiled double-stranded DNA molecules (plasmids) were isolated from plants infected with three laboratory strains of western aster yellows mycoplasma-like organism (AY-MLO) by using cesium chloride-ethidium bromide density gradients. Southern blot analysis, using plasmids from the severe strain of AY-MLO (SAY-MLO) as the probe, identified at least four plasmids in celery, aster, and periwinkle plants and in Macrosteles severini leafhopper vectors infected with either the dwarf AY-MLO, Tulelake AY-MLO, or SAY-MLO strain. Plasmids were also detected in two California field isolates of AY-MLO but not in plants infected with the beet leafhopper-transmitted virescence agent, western X, or elm yellows MLOs. SAY-MLO plasmids were 5.2, 4.9, 3.4, and 1.7 kilobase pairs in size. Plasmids isolated from dwarf AY- and Tulelake AY-MLOs were 7.4, 5.1, 3.5, and 1.7 kilobase pairs in size. No evidence was obtained for integration of SAY-MLO plasmids into the MLO chromosome. PMID- 2307662 TI - A stable variant of Simonsiella muelleri with unusual colonial and cellular morphology. AB - The unusual morphology and cellular arrangement of a member of the genus Simonsiella is described. The organism is characterized by the formation of very long trichomes, which can be greater than 1,000 microns in length. PMID- 2307661 TI - Biochemical characterization of avirulent exoC mutants of Agrobacterium tumefaciens. AB - The synthesis of periplasmic beta(1-2)glucan is required for crown gall tumor formation by Agrobacterium tumefaciens and for effective nodulation of alfalfa by Rhizobium meliloti. The exoC (pscA) gene is required for this synthesis by both bacteria as well as for the synthesis of capsular polysaccharide and normal lipopolysaccharide. We tested the possibility that the pleiotropic ExoC phenotype is due to a defect in the synthesis of an intermediate common to several polysaccharide biosynthetic pathways. Cytoplasmic extracts from wild-type A. tumefaciens and from exoC mutants of A. tumefaciens containing a cloned wild-type exoC gene synthesized in vitro UDP-glucose from glucose, glucose 1-phosphate, and glucose 6-phosphate. Extracts from exoC mutants synthesized UDP-glucose from glucose 1-phosphate but not from glucose or glucose 6-phosphate. Membranes from exoC mutant cells synthesized beta(1-2)glucan in vitro when exogenous UDP-glucose was added and contained the 235-kilodalton protein, which has been shown to carry out this synthesis in wild-type cells. We conclude that the inability of exoC mutants to synthesize beta(1-2)glucan is due to a deficiency in the activity of the enzyme phosphoglucomutase (EC 2.7.5.1), which in wild-type bacteria converts glucose 6-phosphate to glucose 1-phosphate, an intermediate in the synthesis of UDP-glucose. This interpretation can account for all of the deficiencies in polysaccharide synthesis which have been observed in these mutants. PMID- 2307663 TI - Retrospective assessment of DSM-III attention deficit disorder in nonreferred individuals. AB - Using criterion-based structured interview techniques and blind assessment, the authors reported high rates of DSM-III childhood attention deficit disorder (ADD) in nonpatient first-degree relatives (parents and siblings) of 6- to 17-year-old clinically referred probands with ADD compared with rates found in relatives of normal comparison children of the same age. To further examine the validity of the ADD diagnosis in these nonreferred relatives, the authors examined whether the diagnosis was associated with antisocial disorders known to co-occur with ADD. As predicted, they found that relatives with childhood ADD (32% of relatives) were at a significantly higher risk for antisocial disorders (61% vs. 19%, p less than .01) compared with relatives without childhood ADD. In addition, the retrospective diagnosis of ADD among these nonreferred relatives resulted in a pattern of observations that is consistent with the literature on ADD in clinically referred children and adolescents: (1) ADD was more common among males than females; (2) the rate of ADD in a control group was consistent with the known risk of ADD in the general population (5.7%); and (3) 71% of ADD relatives reported levels of symptomatology within the range found in clinically referred children. These findings in a group of unselected and blindly evaluated relatives of ADD children provide indirect support for the validity of the diagnosis of ADD using standardized instruments and operational criteria. PMID- 2307664 TI - The relationship of gender to violent behavior in acutely disturbed psychiatric patients. AB - On the basis of extensive review of the medical records of 253 patients hospitalized in a locked psychiatric unit, the authors found that before hospitalization, men engaged in significantly more physical attacks and fear inducing behavior than did women. During short-term psychiatric hospitalization, although men continued to engage in more fear-inducing behavior, women engaged in proportionately more physical attacks. To control for possible confounding variables, the authors repeated the analyses after stratifying by demographic and diagnostic variables that were distributed differently among men and women. The same pattern of relationships between gender and violence was found. The authors give case examples and discuss possible explanations and implications of the findings. PMID- 2307665 TI - Compliance, the LAQ, and a new laboratory method of measuring RBC lithium. PMID- 2307666 TI - Schizophrenic individuals with bipolar first-degree relatives: analysis of two pedigrees. AB - During the course of a family-interview study of probands with psychotic disorders, the authors encountered two pedigrees in which schizophrenic individuals had first-degree relatives with bipolar disorder. The authors describe the members of both families in detail and discuss several hypotheses that might account for the co-occurrence of schizophrenia and bipolar disorder in the same family. PMID- 2307667 TI - Elicitation of an oxidase activity in bacterial luciferase by site-directed mutation of a noncatalytic residue. AB - Flavin-dependent external monooxygenases and oxidases could catalyze the same flavin oxidation reaction involving distinct mechanisms. To gain insights into enzyme structure-function relationship, site-directed mutagenesis was carried out for Vibrio harveyi luciferase, a monooxygenase. The substitution of the alpha subunit cysteine 106 by alanine shows unambiguously that the alphaCys106 is not essential to catalysis. The corresponding substitution by valine resulted in a substantial reduction of the bioluminescence activity correlatable with the induction of a new flavin oxidation activity typical for oxidases. These findings indicate that mutation of a single noncatalytic residue at the active center of a flavoenzyme could transform one enzyme type to another, thus highlighting the subtlety of enzyme active site structure in relation to catalysis and the versatility of enzyme evolution. PMID- 2307668 TI - Lipoprotein ApoC-II activation of lipoprotein lipase. Modulation by apolipoprotein A-IV. AB - Lipoprotein lipase (LPL)-mediated hydrolysis of triglycerides (TG) contained in chylomicrons requires the presence of a cofactor, apolipoprotein (apo) C-II. The physiological mechanism by which chylomicrons gain apoC-II necessary for LPL activation in whole plasma is not known. Using a gum arabic stabilized TG emulsion, activation of LPL by lipoprotein apoC-II was studied. Hydrolysis of TG by LPL was greater in the presence of serum than with addition of either high density lipoproteins (HDL) or very low density lipoproteins (VLDL). LPL activation by either VLDL or HDL increased with addition of the lipoprotein-free fraction of plasma. A similar increase in LPL activity by addition of the lipoprotein-free fraction together with HDL or VLDL was observed when another TG emulsion (Intralipid) or TG-rich lipoproteins from an apoC-II deficient subject were used as a substrate. Human apoA-IV, apoA-I, apoE, and cholesteryl ester transfer protein were assessed for their ability to increase LPL activity in the presence of VLDL. At and below physiological concentrations, only apoA-IV increased LPL activity. One hundred percent of LPL activity measured in the presence of serum was achieved using VLDL plus apoA-IV. In the absence of an apoC II source, apoA-IV had no effect on LPL activity. Removal of greater than 80% of the apoA-IV from the nonlipoprotein-containing fraction of plasma by incubation with Intralipid markedly reduced its ability to activate LPL in the presence of VLDL or HDL. Gel filtration chromatography demonstrated that incubation of the nonlipoprotein-containing fraction of plasma with HDL and the TG emulsion caused increased transfer of apoC-II to the emulsion and association of apoA-IV with HDL. Our studies demonstrate that apoA-IV increases LPL activation in the presence of lipoproteins. We hypothesize that apoA-IV is required for efficient release of apoC-II from either HDL or VLDL, which then allows for LPL-mediated hydrolysis of TG in nascent chylomicrons. PMID- 2307669 TI - Metabolism of 15-hydroxy-5,8,11,13-eicosatetraenoic acid by MOLT-4 cells and blood T-lymphocytes. AB - MOLT-4 lymphocytes metabolize 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15 HETE) via beta-oxidation with retention of the hydroxyl group at the omega 6 carbon atom. 15-HETE oxidation is accompanied by the time-dependent accumulation of both beta-hydroxy acids and metabolites produced by repetitive cycles of the beta-oxidation spiral. Detection of 7-hydroxy-5-dodecenoic acid shows that these cells continue to beta-oxidize the substrate when the conjugated diene is allylic to a hydroxyl group. When 15-HETE was the substrate, it was also possible to detect 12-hydroxy-5,8,10-heptadecatrien-1-al and 3,15-dihydroxy-8,11,13 eicosatrienoic acid. The former product may be produced by alpha-oxidation of 13 hydroxy-6,9,11-octadecatrienoic acid followed by its decarboxylation. Detection of a 20-carbon metabolite, lacking a double bond at position 5, suggests that an intermediate of beta-oxidation was used as a substrate for chain elongation. When 13-hydroxy-6,9,11-octadecatrienoic acid was used as a substrate, it was indeed possible to detect 3,15-dihydroxy-8,11,13-eicosatrienoic acid as well as 15 hydroxy-8,11,13-eicosatrienoic acid. In addition, 13-hydroxy-6,9,11 octadecatrienoic acid was a precursor for the biosynthesis of both 14-hydroxy 7,10,12-nonadecatrien-1-al and 1,14-dihydroxy-7,10,12-nonadecatriene. These studies with MOLT-4 cells as well as with T-lymphocytes isolated from blood show that products of the 15-lipoxygenase pathway are metabolized with the accumulation of a variety of compounds. Since 15-HETE has been implicated as a modulator of T-cell function, these findings raise the possibility that the newly described metabolites may be involved in regulating lymphocyte function. PMID- 2307670 TI - Microtubule oscillations. Role of nucleation and microtubule number concentration. AB - Microtubules are capable of performing synchronized oscillations of assembly and disassembly which has been explained by reaction mechanisms involving tubulin subunits, oligomers, microtubules, and GTP. Here we address the question of how microtubule nucleation or their number concentration affects the oscillations. Assembly itself requires a critical protein concentration (Cc), but oscillations require in addition a critical microtubule number concentration (CMT). In spontaneous assembly this can be achieved with protein concentrations Cos well above the critical concentration Cc because this enhances the efficiency of nucleation. Seeding with microtubules can either generate oscillations or suppress them, depending on how the seeds alter the effective microtubule number concentration. The relative influence of microtubule number and total protein concentrations can be varied by the rate at which assembly conditions are induced (e.g. by a temperature rise): Fast T-jumps induce oscillations because of efficient nucleation, slow ones do not. Oscillations become damped for several reasons. One is the consumption of GTP, the second is a decrease in microtubule number, and the third is that the ratio of microtubules in the two phases (growth competent and shrinkage-competent) approach a steady state value. This ratio can be perturbed, and the oscillations restarted, by a cold shock, addition of seeds, addition of GTP, or fragmentation. Each of these is equivalent to a change in the effective microtubule number concentration. PMID- 2307671 TI - Generation of diversity in nonerythroid spectrins. Multiple polypeptides are predicted by sequence analysis of cDNAs encompassing the coding region of human nonerythroid alpha-spectrin. AB - Nonerythroid alpha-spectrin (alpha-fodrin) is a major component of the membrane skeleton in diverse cell types. Overlapping cDNAs have been isolated which encompass the coding region of human lung fibroblast nonerythroid alpha-spectrin. The composite sequence of 7,787 nucleotides encodes a polypeptide of 2,472 amino acids (predicted Mr of 283,964). This sequence has 58% amino acid identity with human erythroid alpha-spectrin, which is encoded on a different gene, and 96% amino acid identity with the full-length sequence of chicken brain alpha spectrin. We previously reported the variable expression in human fibroblast alpha-spectrin of 20 amino acids between repeats 10 and 11 (McMahon, A. P., Giebelhaus, D. H., Champion, J. E., Bailes, J. A., Lacey, S., Carritt, B., Henchman, S. K., and Moon, R. T. (1987) Differentiation 34, 68-78). In this study, we report additional heterogeneity in fibroblast alpha-spectrin near the carboxyl-terminal end. One of the fibroblast cDNAs (clone 3D) has an in-frame deletion of 18 nucleotides within spectrin repeat 21 when compared to an overlapping fibroblast cDNA (clone 7). As this heterogeneity in amino acid sequence occurs near domains of nonerythroid alpha-spectrin suggested to bind calcium or actin, it is possible that fibroblasts express functionally distinct isoforms of nonerythroid alpha-spectrin. PMID- 2307672 TI - Hormonal discrimination among transcription start sites of aspartate aminotransferase. AB - The promoter of the gene coding for the rat cytosolic aspartate aminotransferase was cloned from a Charon 4A genomic library. We have sequenced a 1.1-kilobase PstI-PstI fragment which contains the first exon of the gene, the beginning of the first intron and 682 base pairs of the 5' regulatory region (+1 being the A of the first ATG codon), which exhibits promoter activity. The promoter region is G + C rich, does not include any TATA-like element, but has 4 putative Sp1 binding sites and 6 regularly spaced CCAAT boxes. The promoter activity of the 5' regulatory region, as well as its sensitivity to glucocorticoids, were assessed by transient gene expression assays after fusion to the chloramphenicol acetyltransferase gene in the hepatoma cell lines HepG2 and Fao. Multiple transcription start sites were found on the gene over a short distance (55 base pairs), but they were differentially regulated by glucocorticoids as determined by both primer extension analysis and S1 mapping. In particular, transcription from 2 start sites was increased 15- to 18-fold, whereas transcription from the 3 other ones was increased 3-fold. In addition, three new start sites, below the detection limit in control cells, were highly induced. Therefore, a hormonal regulatory element can discriminate among closely related transcription start sites. PMID- 2307673 TI - Dynamics and reactivity of HbXL99 alpha. A cross-linked hemoglobin derivative. AB - Resonance Raman spectroscopy, transient absorption, and fluroescence techniques have been employed to investigate the structure and dynamics of the alpha-cross linked hemoglobin derivative, HbXL99 alpha. The resonance Raman spectra of the deoxy form of HbXL99 alpha are identical to those of native NbA (VFe-His approximately 222 cm-1), which exhibit a T-state (low affinity) structure regardless of solvent conditions. The resonance Raman spectra of the transient heme photoproduct resulting from CO photolysis from HbXL99 alpha appear to have structures intermediate between deoxy-T and ligand-bound R structures (VFe-His approximately 222 cm-1). Time-resolved resonance Raman data of HbXL99 alpha-CO show that complete CO recombination occurs after approximately 5 ms, with only a small amount of the CO-bound species reforming within approximately 200 ns (geminate recombination). Transient absorption spectra of HbXL99 alpha-O2 indicate that the extent of sub-nanosecond geminate recombination of O2 is also reduced in the cross-linked derivative relative to native HbA. The decrease in tryptophan fluorescence of HbXL99 alpha upon oxygenation further indicates that tertiary structural changes at the alpha 1-beta 2 interface upon ligation are apparently reduced, but not eliminated in the cross-linked derivative relative to HbA. PMID- 2307674 TI - Alternative ribosomal initiation gives rise to chicken brain-type creatine kinase isoproteins with heterogeneous amino termini. AB - In higher eukaryotes three different types of creatine kinases (CK) are expressed: the muscle-specific M-CK, the ubiquitous cytoplasmic B-CKs, and the mitochondrial Mi-CKs. They fulfill multiple tasks in cells with an intensive energy metabolism. Isolated chicken B-CK can be resolved by two-dimensional gel electrophoresis into a major acidic Ba-CK and a major basic Bb-CK protein species which are very likely produced from the unique chicken B-CK gene (Wirz, T., Hossle, J. P., Soldati, T., and Perriard, J.-C. (1989) Experientia (Basel) 45, 32 (abstr.]. However, close inspection of the gels indicates the presence of additional B-CK species. This additional heterogeneity is generated by two distinct post-transcriptional processes. Post-translational phosphorylation was shown to contribute to heterogeneity of both Ba- and Bb-CK isoproteins and appears to modulate their enzymatic activity (A. F. Q. Quest, H. M. Eppenberger, and T. Wallimann, manuscript in preparation). Alternative ribosomal initiation of Bb-CK synthesis at multiple sites was shown to occur in cell free systems as well as in vivo, resulting in proteins differing in the length of their amino termini. Using site-directed mutagenesis to "switch off" each of the first four methionine codons of a full length Bb-CK cDNA, we were able to correlate each protein product with one distinct translational start site. An additional protein species appears to be produced by initiation at a noncanonical start codon. We propose that a leucine codon may be used as a translational start site. Evidence is presented to support the role of these amino-terminal truncated subunits in the regulation of the enzyme. PMID- 2307675 TI - Purification, crystallization, and preliminary X-ray diffraction analysis of rat kidney annexin V, a calcium-dependent phospholipid-binding protein. AB - We have purified annexin V, a monomeric 35-kDa protein, from rat kidney using calcium-dependent phospholipid chromatography. The identity of annexin V was confirmed by immunoblot analysis using monospecific anti-annexin V antibody. Large single crystals of annexin V in the presence of calcium have been grown from ammonium sulfate under a variety of conditions, with an optimum pH range of 7.5-8.0. The crystals diffract to at least 2.2 A Bragg spacing and are stable to x-rays. Preliminary crystallographic analysis reveals the space group to be R3, with hexagonal cell dimensions of a = b = 156.8 A and c = 36.9 A, and there is one molecule/asymmetric unit. PMID- 2307676 TI - The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation. AB - The regulation of adipose tissue lipoprotein lipase (LPL) was examined in rats fed or fasted overnight, and was found to be controlled posttranslationally. LPL catalytic activity decreased by 50% after fasting while LPL mRNA levels and rates of synthesis increased nearly 2-fold; enzyme mass remained unchanged. The distribution of LPL within the endoplasmic reticulum (ER) and Golgi/post-Golgi secretory pathway was assessed by differentiating between LPL high mannose and complex forms. After fasting, the majority of LPL is in the high mannose ER form (65%, 0.97 micrograms/g wet weight tissue), whereas the LPL complex form comprises only 35% (or 0.52 micrograms/g). After refeeding, however, the Golgi derived LPL complex form predominates (65%, 1.03 micrograms/g) over the high mannose ER form (35%, 0.55 micrograms/g). Kinetic analysis suggests that high mannose LPL disappears with a half-life of t0.5 = 40 min in both fed and fasted rats, indicating that the redistribution of LPL mass during feeding/fasting does not arise by differential retention within ER. Instead, the fractional catabolic rate of complex LPL within the Golgi/post-Golgi secretory compartment can be calculated to be 3.5-fold greater in fasting. In heart, changes in LPL activity in response to feeding/fasting are also not due to differences in mRNA levels or rates of synthesis. Based on these findings, a model of LPL posttranslational regulation is proposed and discussed. PMID- 2307677 TI - Amino acid sequence and characterization of a protein inhibitor of protein kinase C. AB - The complete primary structure has been determined for an inhibitor protein of protein kinase C. The bovine brain-derived inhibitor has a pI of 6 and its N terminal alanine residue is blocked by acetylation. Fragments obtained by chemical and enzymatic cleavage of the purified inhibitor were analyzed by Edman degradation, fast atom bombardment mass spectrometry, and tandem mass spectrometry. The results establish that the protein has a calculated average molecular mass of 13,690 daltons and contains 125 amino acid residues with the following sequence: (sequence: see text) The inhibitor does not show significant homology with any other known protein. Circular dichroism of the freshly prepared apoprotein indicated a secondary structural content of 23% alpha-helix, 31% beta sheet, and 11% beta-turn. Immobilization on nitrocellulose followed by exposure to a 65Zn2(+)-containing overlay solution showed that, like protein kinase C itself, the inhibitor is a zinc-binding protein, although the sequence does not reveal a "zinc finger" structure. Competition with 10-fold molar excess Ca2+ or Mg2+ did not reduce the zinc-binding specificity of this inhibitor. PMID- 2307678 TI - The transcription complex of the Xenopus somatic 5 S RNA gene. A functional analysis of protein-DNA interactions outside of the internal control region. AB - We have defined protein-DNA interactions associated with the transcription complex of a Xenopus somatic 5 S RNA gene under efficient in vitro transcription conditions. Transcription factor IIIA, the internal control region of the 5 S RNA gene and specific DNA sequences 5' and 3' of the internal control region are all involved in the formation of a multiprotein complex. Specific protein-DNA interactions outside of the 5 S RNA gene itself, revealed by DNase I footprinting, have no apparent role in the transcription process. Sequences within the 5 S RNA gene, 5' of the internal control region, are not essential for transcription by RNA polymerase III in vitro, but do contribute to its efficiency. PMID- 2307679 TI - Rat peroxisomal 3-ketoacyl-CoA thiolase gene. Occurrence of two closely related but differentially regulated genes. AB - We isolated and analyzed the genes for rat peroxisomal 3-ketoacyl-CoA thiolase. Two active genes (termed A and B), both likely to be coding for the peroxisomal thiolase, were identified per haploid rat genome. These genes span approximately 9 and 11 kilobases, respectively, and both contain 12 exons and 11 introns, with overall similar organizations. The nucleotide sequences are highly conserved in the coding regions and in many introns. The A and B genes code for slightly different amino acid sequences, and the known cDNA sequence (Hijikata, M., Ishii, N., Kagamiyama, H., Osumi, T., and Hashimoto, T. (1987) J. Biol. Chem. 262, 8151 8158) corresponds to the B gene product. By in vitro transcription/translation, the A gene was shown to produce a thiolase precursor having a 10-residue longer amino-terminal presequence than that of the B gene product. Primer extension analysis revealed that the A gene is constitutively expressed and is not influenced by the administration of a peroxisome proliferator, whereas the B gene is markedly activated by the same treatment. Several common sequences were noted in the 5'-flanking regions of the B gene and in the genes of two other peroxisomal beta-oxidation enzymes, induced in parallel by peroxisome proliferators. PMID- 2307680 TI - Nucleotide sequence and estrogen induction of Xenopus laevis 3-hydroxy-3 methylglutaryl-coenzyme A reductase. AB - We have isolated and sequenced overlapping cDNA clones encompassing the entire protein coding region of Xenopus laevis 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). This 3-kilobase cDNA codes for an 883-amino acid protein, which exhibits extensive amino acid sequence homology to mammalian HMG CoA reductases. The highly conserved 341-amino acid membrane spanning domain exhibits 89% amino acid sequence identity with hamster HMG-CoA reductase. In contrast to the high degree of homology in the coding regions of the mRNAs, the nucleotide sequences of the 5'- and 3'-untranslated regions of Xenopus and mammalian HMG-CoA reductase mRNAs exhibit negligible homology. Primer extension data suggests that Xenopus HMG-CoA reductase mRNA is transcribed from multiple initiation sites. The Xenopus HMG-CoA reductase cDNA clones were used as hybridization probes to examine estrogen regulation of hepatic HMG-CoA reductase mRNA levels. Northern blot analysis demonstrates that estradiol-17 beta induced HMG-CoA reductase mRNA in livers of male X. laevis 10-fold within 24 h. Reductase mRNA levels reach a plateau 23-fold higher than basal levels between 5 and 8 days after initial estrogen administration. In contrast to the vitellogenin and retinol binding protein genes whose transcription is induced by estrogen in Xenopus liver, the runoff transcription rate of HMG-CoA reductase does not increase significantly on administration of estradiol-17 beta. These data suggest that the estrogen induction of HMG-CoA reductase mRNA may be achieved through posttranscriptional mechanisms. PMID- 2307681 TI - Role of upstream sequences in the expression of the staphylococcal enterotoxin B gene. AB - The staphylococcal enterotoxin B gene (seb) is positively regulated at the transcriptional level (Gaskill, M. E., and Khan, S. A. (1988) J. Biol. Chem. 263, 6276-6280). The sequences involved in the regulation of transcription of the seb gene have been studied by deletion analysis. A multicopy Staphylococcus aureus plasmid carrying the cloned seb gene was used to generate a series of mutants that are deleted in the upstream region of this gene. The levels of enterotoxin B protein and mRNA produced by the deletion mutants were analyzed. A region between 59 and 93 nucleotides upstream of the transcription initiation site was found to be required for transcription and expression of the seb gene. Deletion of this sequence greatly reduced or eliminated transcription of the seb gene. DNA-protein binding experiments showed that cell-free extracts made from an staphylococcal enterotoxin B-producing strain contain protein(s) that specifically bind to the upstream region. This protein may be involved in the transcriptional activation of the seb gene. PMID- 2307682 TI - DNA damage promotes jumping between templates during enzymatic amplification. AB - Pairs of templates and primers were designed so that only recombination events would lead to amplification via the polymerase chain reaction. This approach reveals that lesions such as breaks, apurinic sites, and UV damage in a DNA template can cause the extending primer to jump to another template during the polymerase chain reaction. By comparing sequences of amplification products that were determined directly or via bacterial cloning, it was shown that when the thermostable Thermus aquaticus DNA polymerase encounters the end of a template molecule, it sometimes inserts an adenosine residue; the prematurely terminated product then jumps to another template and polymerization continues, creating an in vitro recombination product. Consequently, amplification products from damaged templates such as archaeological DNA are made up of a high proportion of chimeric molecules. The illegitimate adenosine and thymidine residues in these molecules are detected when cloned molecules are sequenced, but are generally averaged out when the amplification product is sequenced directly. However, if site-specific lesions exist in template DNA or if the amplification is initiated from very few copies, direct sequencing also may yield incorrect sequences. The phenomenon of the "jumping polymerase chain reaction" can be exploited to assess the frequency and location of lesions in nucleic acids. PMID- 2307683 TI - Leiurotoxin I (scyllatoxin), a peptide ligand for Ca2(+)-activated K+ channels. Chemical synthesis, radiolabeling, and receptor characterization. AB - Leiurotoxin I (scyllatoxin) is a 31-amino acid polypeptide from the venom of the scorpion Leiurus quinquestriatus hebraeus which has been previously isolated and sequenced by others. This paper reports (i) the total synthesis of this scorpion neurotoxin as well as some aspects of its structure-function relationships; (ii) the synthesis of the analog [Tyr2]leiurotoxin I (scyllatoxin) that has been monoiodinated at high specific radioactivity (2000 Ci/mmol) and has served for the characterization of the properties of 125I-[Tyr2]leiurotoxin I binding sites (Kd = 80 pM, molecular mass of 27 and 57 kDa for two polypeptides in the leiurotoxin I binding protein); (iii) the similarity of physiological actions between leiurotoxin I and apamin. Both toxins contract Taenia coli previously relaxed with epinephrine, both toxins block the after-hyperpolarization due to Ca2(+)-activated K+ channel activity in muscle cells in culture; (iv) the probable identity of binding sites for apamin and leiurotoxin I. In spite of a different chemical structure apamin competitively inhibits 125I-[Tyr2] leiurotoxin I binding and vice versa. Moreover, the peculiar effects of K+ on 125I-[Tyr2]leiurotoxin I binding are identical to those previously observed for 125I-apamin binding. PMID- 2307685 TI - Correction: characterization of the virB operon from Agrobacterium tumefaciens Ti plasmid. PMID- 2307684 TI - The effects of foreign transmembrane domains on the biosynthesis of the influenza virus hemagglutinin. AB - Eleven chimeric proteins were created in which the transmembrane, the cytoplasmic, or both topological domains of the influenza virus hemagglutinin (HA) were replaced with those from five other glycoproteins. All of the chimeric HAs reached the cell surface but appeared to differ in the degree to which they were stably folded. Comparisons of the rates of folding, passage into the Golgi, and arrival at the plasma membrane of wild-type HA and the chimeric proteins suggest that formation of a stable HA trimer is not an absolute requirement for export from the endoplasmic reticulum. In addition, there appear to be at least two steps at which the rate of transport can be altered during exocytosis, one occurring before and the other after the trimming of oligosaccharides by Golgi mannosidases. Certain of the chimeras differed from HA in their ability to pass through each of these steps. Replacement of the HA transmembrane domain with the analogous sequences from other proteins affected folding and transport of the chimeric HAs in ways that suggest that the HA transmembrane sequences form a specific structure in the membrane that differs from that formed by analogous sequences from the other proteins. PMID- 2307686 TI - Femoral head apparent density distribution predicted from bone stresses. AB - A new theory relating bone morphology to applied stress is used to predict the apparent density distribution in the femoral head and neck. Cancellous bone is modeled as a self-optimizing material and cortical bone as a saturated (maximum possible bone density) response to stress in the bone tissue. Three different approaches are implemented relating bone apparent density to: (1) the von Mises stress, (2) the strain energy density in the mineralized tissue and (3) a defined closed effective stress (spherical stress). An iterative nonlinear three dimensional finite element model is used to predict the apparent density distribution in the femoral head and neck for each of the three approaches. It is shown that the von Mises stress (an open effective stress) cannot accurately predict bone apparent density. It is shown that strain energy density and the defined closed effective stress can predict apparent density and that they give predictions consistent with the observed density pattern in the femoral head and neck. PMID- 2307688 TI - Study of stress concentration in the walls of the bovine coronary arterial branch. AB - The intramural stress concentration in the arterial wall is studied at the bovine circumflex coronary arterial branch. The material properties, geometry, and strains in the arterial branch are determined from experiments. The stresses are determined using a finite element analysis. The arterial branch is modeled as two interesecting thin cylindrical shells incorporating local variations in the branch geometry, thickness, and material properties. The artery is considered orthotropic and loaded with an incremental pressure of 40 mmHg. The highest intramural stresses are found to be localized at the proximal and distal regions of the ostium and are not significantly affected by the elastic properties. The stresses are 3 to 4 times greater in the branch at the inner surface than in the straight segment. The strains are twice as large at the branch than in the straight segment. We speculate that this stress concentration could injure the artery and make the branch region susceptible to atherosclerosis. PMID- 2307689 TI - A new theoretical model for noninvasive quantification of mitral regurgitation. AB - The most common objective assessments of mitral regurgitation are limited by their invasive or semiquantitative nature. Recent attempts at correlation with jet size from Doppler flow maps have failed to produce a direct measure of regurgitant volume and are fundamentally limited by the dependence of jet dimensions on factors other than flow volume. The purpose of this paper was to develop an equation, based on the physics of turbulent regurgitant jets, for calculating regurgitant volume from quantities that can be measured by Doppler ultrasound. The result is an equation forw flow rate Q as a function of orifice velocity Uo, a downstream centerline velocity Um and the intervening distance chi: Q = pi U2m chi 2/160Uo. This equation can also be modified to obtain total regurgitant volume in clinical pulsatile flow. The assumptions made demand a free turbulent jet for which momentum is conserved, but should otherwise be physiologically applicable. The advantage of this technique compared to correlations with jet size are its theoretical justification and ability to quantify regurgitant volume directly. PMID- 2307687 TI - Deviatoric and hydrostatic mode interaction in hard and soft tissue. AB - It has been established that many hard and soft tissues have anisotropic material symmetry. It is noted here that the deviatoric and hydrostatic modes interact with each other in a general anisotropic elastic material. In the special case of isotropic, linear elastic, materials these modes are non-interactive. As a consequence of the interaction of these modes encountered in anisotropic materials, the decomposition into hydrostatic and deviatoric modes, and deviatoric mode concepts such as the von Mises effective stress are not appropriate for anisotropic materials in general. The implications of this observation for the presentation of computationally generated stress contours for hard and soft tissues are discussed. It is also pointed out that the mode coupling and mode interaction raise the question of whether anisotropic living tissues respond directly to stress or to some other physical quantity such as strain or strain energy, in view of the recent hypothesis concerning the proliferation and ossification of cartilage. PMID- 2307690 TI - In vitro analysis of a model of intracardiac jet: analysis of the central core of axisymmetric jets. AB - In order to provide physical information supporting the clinical use of flow mapping, an in vitro model was designed to measure the velocity fields in a pulsatile hydraulic turbulent jet. We used a peak velocity ranging from 2.5 to 5.5 m.s-1, an orifice diameter ranging from 5.8 to 11.3 mm and confined the jet in a receiving tube whose diameter ranged from 16 to 30 mm, thus simulating a large variety of valvular leaks. In steady flow conditions, our results agreed with previously reported descriptions. Under pulsatile conditions, the same structure was found at peak velocity and during the beginning of the deceleration. Below a threshold velocity, the length of the central core was independent of the peak velocity and proportional to about six times the orifice diameter. Above the threshold velocity, this relationship was no longer true, the threshold value being related to the ratio of the orifice diameter to the diameter of the receiving tube. PMID- 2307691 TI - Prediction of total knee motion using a three-dimensional computer-graphics model. AB - Twenty-three knees were sectioned, digitized, and standardized to determine the 'average' three-dimensional bony geometry and ligamentous attachments. Data on normal knee motion were obtained from a cadaveric study. An algorithm was written to simulate three-dimensional patella motion. Verification of the knee model was achieved by determining femoro-tibial and patello-femoral contact locations, as well as ligament length patterns, and comparing the results with published data. The criterion for maximum predicted knee motion with a prosthesis in place was the length of the posterior cruciate ligament. Three total knee replacement surfaces were mathematically generated: flat, laxity and conforming. A greater flexion angle was obtained with a flat tibial surface than for the laxity or conforming. Posterior tibial component displacement increased the range of motion, but only slightly. For all tibial surfaces, increased range of motion was achieved with a 10 degrees posterior tilt of the tibial tray. Anterior femoral component displacement increased motion due to reduction in posterior cruciate tension during flexion. The results are applicable to the design and surgical technique of total knee replacement. PMID- 2307692 TI - The simulation of aerial movement--I. The determination of orientation angles from film data. AB - Quantitative mechanical analyses of human movement require the time histories of the angles which specify body configuration and orientation. When these angles are obtained from a filmed performance they may be used to evaluate the accuracy of a simulation model. This paper presents a method of determining orientation angles and their rates of change from film data. The stages used comprise the synchronization of data obtained from two camera views, the determination of three-dimensional coordinates of joint centres, the calculation of an angle from a sequence of sine and cosine values and the curve fitting of angles using quintic splines. For each stage, other possible approaches are discussed. Original procedures are presented for obtaining individual error estimates of both the film data and the calculated angles to permit the automatic fitting of quintic splines for interpolation and differentiation and for deriving the time history of an angle as a continuous function from a sequence of sine and cosine values. The method is applied to a forward somersault with 1 1/2 twists and the average error estimate of 17 orientation angles is obtained as 2.1 degrees. PMID- 2307693 TI - The simulation of aerial movement--II. A mathematical inertia model of the human body. AB - A mathematical inertia model which permits the determination of personalized segmental inertia parameter values from anthropometric measurements is described. The human body is modelled using 40 geometric solids which are specified by 95 anthropometric measurements. A 'stadium' solid is introduced for modelling the torso segments using perimeter and width measurements. This procedure is more accurate than the use of elliptical discs of given width and depth and permits a smaller number of such solids to be used. Inertia parameter values may be obtained for body models of up to 20 segments. Errors in total body mass estimates from this and other models are discussed with reference to the unknown lung volumes. PMID- 2307694 TI - The simulation of aerial movement--III. The determination of the angular momentum of the human body. AB - A method is presented for determining the angular momentum of the human body about its mass centre for general three-dimensional movements. The body is modelled as an 11 segment link system with 17 rotational degrees of freedom and the angular momentum of the body is derived as a sum of 12 terms, each of which is a vector function of just one angular velocity. This partitioning of the angular momentum vector gives the contribution due to the relative segmental movement at each joint rather than the usual contribution of each segment. A method of normalizing the angular momentum is introduced to enable the comparison of rotational movements which have different flight times and are performed by athletes with differing inertia parameters. Angular momentum estimates were calculated during the flight phases of nine twisting somersaults performed on trampoline. Errors in film digitization made large contributions to the angular momentum error estimates. For individual angular momentum estimates the relative error is estimated to be about 10% whereas for mean angular momentum estimates the relative error is estimated to be about 1%. PMID- 2307695 TI - The simulation of aerial movement--IV. A computer simulation model. AB - A computer simulation model of human airborne movement is described. The body is modelled as 11 rigid linked segments with 17 degrees of freedom which are chosen with a view to modelling twisting somersaults. The accuracy of the model is evaluated by comparing the simulation values of the angles describing somersault, tilt and twist with the corresponding values obtained from film data of nine twisting somersaults. The maximum deviations between simulation and film are found to be 0.04 revolutions for somersault, seven degrees for tilt and 0.12 revolutions for twist. It is shown that anthropometric measurement errors, from which segmental inertia parameters are calculated, have a small effect on a simulation, whereas film digitization errors can account for a substantial part of the deviation between simulation and film values. PMID- 2307696 TI - Muscle fiber architecture in the human lower limb. PMID- 2307697 TI - Correction for skin displacement errors in movement analysis of the horse. AB - In movement analysis of the horse, large errors result from movements of the skin with respect to the underlying bones. A generally applicable, two-dimensional, method for correction of these skin-movement errors in kinematic data has been developed. It was tested on a kinematic analysis of the hindlimb in a walking pony. The results indicate that without correction for skin-movement errors, misreadings of up to 15 degrees in the knee angle and 30% in the moment arm of the gastrocnemius muscle can be expected. PMID- 2307698 TI - An N-ethylmaleimide-sensitive cytosolic factor necessary for nuclear protein import: requirement in signal-mediated binding to the nuclear pore. AB - We described previously an assay for authentic nuclear protein import in vitro. In this assay, exogenous nuclei are placed in an extract of Xenopus eggs; a rhodamine-labeled protein possessing a nuclear localization signal is added, and fluorescence microscopy is used to measure nuclear uptake. The requirement in this system for a cytosolic extract suggests that nuclear import is dependent on at least one cytosolic factor. We now confirm this hypothesis. Treatment of the cytosol with N-ethylmaleimide (NEM) abolishes nuclear protein import; readdition of a cytosolic fraction to the NEM-inactivated extract rescues transport. Thus, at least one NEM-sensitive factor required for transport is supplied by the cytosol. This activity, called nuclear import factor-1, or NIF-1, is ammonium sulfate-precipitable, protease-sensitive, and heat-labile; it is therefore at least partly proteinaceous. NIF-1 stimulates, in a concentration-dependent manner, the rate at which individual nuclei accumulate protein. The effect of NIF 1 is enhanced by a second cytosolic NEM-sensitive factor, NIF-2. Earlier we identified two steps in the nuclear import reaction: (a) ATP-independent binding of a signal-sequence-bearing protein to the nuclear pore; and (b) ATP-dependent translocation of that protein through the pore. We now show that NEM inhibits signal-mediated binding, and that readdition of NIF-1 restores binding. Thus, NIF 1 is required for at least the binding step and does not require ATP for its activity. NIF-1 may act as a cytoplasmic signal receptor that escorts signal bearing proteins to the pore, or may instead promote signal-mediated binding to the pore in another manner, as discussed. PMID- 2307699 TI - Nucleocytoplasmic transport is enhanced concomitant with nuclear accumulation of epidermal growth factor (EGF) binding activity in both 3T3-1 and EGF receptor reconstituted NR-6 fibroblasts. AB - Measurements of nucleocytoplasmic transport of fluorescent-labeled macromolecules were performed in both an EGF-nonresponsive mutant fibroblast line (3T3-NR6) and in the same cell line reconstituted with active EGF receptors derived from rat hepatic membrane fraction. Immunolocalization studies of exogenously incorporated EGF receptors in reconstituted 3T3-NR6 fibroblasts demonstrated predominantly intracellular localization. The EGF receptor constructs also showed EGF stimulated incorporation of [3H]thymidine, providing biochemical evidence for functional integration of the exogenously supplied EGF receptors into the reconstituted fibroblasts. Additional support for the functional incorporation of receptor may be inferred from the enhanced cellular accumulation of 125I-EGF in cells treated with chloroquine and leupeptin. 125I-EGF binding and transnuclear macromolecular transport measurements in mutant and reconstituted cells, in conjunction with such measurements on nuclei isolated from these cells, provide data consistent with a growth factor/nuclear signaling mechanism dependent on the nuclear acquisition of EGF binding activity from the plasma membrane. PMID- 2307700 TI - Core filaments of the nuclear matrix. AB - The nuclear matrix is concealed by a much larger mass of chromatin, which can be removed selectively by digesting nuclei with DNase I followed by elution of chromatin with 0.25 M ammonium sulfate. This mild procedure removes chromatin almost completely and preserves nuclear matrix morphology. The complete nuclear matrix consists of a nuclear lamina with an interior matrix composed of thick, polymorphic fibers and large masses that resemble remnant nucleoli. Further extraction of the nuclear matrices of HeLa or MCF-7 cells with 2 M sodium chloride uncovered a network of core filaments. A few dark masses remained enmeshed in the filament network and may be remnants of the nuclear matrix thick fibers and nucleoli. The highly branched core filaments had diameters of 9 and 13 nm measured relative to the intermediate filaments. They may serve as the core structure around which the matrix is constructed. The core filaments retained 70% of nuclear RNA. This RNA consisted both of ribosomal RNA precursors and of very high molecular weight hnRNA with a modal size of 20 kb. Treatment with RNase A removed the core filaments. When 2 M sodium chloride was used directly to remove chromatin after DNase I digestion without a preceding 0.25 M ammonium sulfate extraction, the core filaments were not revealed. Instead, the nuclear interior was filled with amorphous masses that may cover the filaments. This reflected a requirement for a stepwise increase in ionic strength because gradual addition of sodium chloride to a final concentration of 2 M without an 0.25 M ammonium sulfate extraction uncovered core filaments. PMID- 2307701 TI - Heterogeneity of mRNA and protein products arising from the protein 4.1 gene in erythroid and nonerythroid tissues. AB - Immunologically cross-reactive isoforms of the cytoskeletal element protein 4.1 have been identified in many tissues in which they exhibit heterogeneity of molecular weight, abundance, and intracellular localization. To examine the basis for isoform production in erythroid and nonerythroid tissues, we have compared the structure and expression of cDNAs isolated from human erythroid and nonerythroid sources. We have encountered cDNAs representing many distinct mRNA sequences. These exhibit complete nucleotide sequence homology along most of their lengths. Differences were confined to five sequence blocks designated Motifs I-V, which were present or absent in each mRNA moiety. Motif I was expressed only in erythroid cells; it encodes 21 amino acids in a well characterized spectrin/actin binding domain. Motif II, located near the COOH terminus of the 80-kD "erythroid" protein 4.1 molecule is present in the vast majority of transcripts from both erythroid and nonerythroid cells. Motifs IV and V alter the 5' untranslated region: simultaneous insertion of Motif IV and deletion of Motif V in the untranslated region inserts a new initiator methionine and establishes a contiguous open reading frame encoding a novel 135-kD protein 4.1 molecule. By immunochemical analysis we have identified the longer isoform in cells. Our results are most consistent with tissue-specific alternative mRNA splicing of transcripts of the protein 4.1 gene to yield numerous isoforms. These isoforms exhibit tissue specificity and alter strategic portions of the molecule. Moreover, we describe a novel high molecular weight form of protein 4.1 that arises by splicing events which allow translation at an upstream site. PMID- 2307702 TI - Membrane-enclosed crystals in Dictyostelium discoideum cells, consisting of developmentally regulated proteins with sequence similarities to known esterases. AB - Developing cells of Dictyostelium discoideum contain crystalline inclusion bodies. The interlattice spaces of the crystals are approximately 11 nm, and their edge dimensions vary in aggregating cells from 0.1 to 0.5 micron. The crystals are enclosed by a membrane with the characteristics of RER. To unravel the nature of the crystals we isolated them under electron microscopical control and purified the two major proteins that cofractionate with the crystals, one of an apparent molecular mass of 69 kD, the other of 56 kD. This latter protein proved to be identical with the protein encoded by the developmentally regulated D2 gene of D. discoideum, as shown by its reactivity with antibodies raised against the bacterially expressed product of a D2 fusion gene. The D2 gene is known to be strictly regulated at the transcript level and to be controlled by cAMP signals. Accordingly, very little of the 56-kD protein was detected in growth phase cells, maximal expression was observed at the aggregation stage, and the expression was stimulated by cAMP pulses. The 69-kD protein is the major constituent of the crystals and is therefore called "crystal protein." This protein is developmentally regulated and accumulates in aggregating cells similar to the D2 protein, but is not, or is only slightly regulated by cAMP pulses. mAbs specific for either the crystal protein or the D2 protein, labeled the intracellular crystals as demonstrated by the use of immunoelectron microscopy. The complete cDNA-derived amino acid sequence of the crystal protein indicates a hydrophobic leader and shows a high degree of sequence similarity with Torpedo acetylcholinesterase and rat lysophospholipase. Because the D2 protein also shows sequence similarities with various esterases, the vesicles filled with crystals of these proteins are named esterosomes. PMID- 2307704 TI - Differential distribution of myosin isoforms among the myofibrils of individual developing muscle fibers. AB - Myosin was localized in situ in the posthatch chicken pectoralis using isoform specific mAbs. The distribution among myofibrils was demonstrated by immunofluorescence and by immunogold EM. Fluorescein- or rhodamine-labeled antibody (12C5) specific for the head region (S1) of myosin was used as a marker to identify "embryonic" myosin. In longitudinal semithin frozen sections, a minority population of myofibrils stained intensely with 12C5. All other myofibrils in the same cell stained only weakly. Similarly, in Lowicryl-embedded ultrathin sections prepared for EM, a minority population reacted preferentially with gold-labeled 12C5. An antibody (5B4) specific for the rod portion of "neonatal" myosin reacted strongly with nearly all myofibrils, and this was evident by light and electron microscopy. A few of the fibrils that reacted strongly with 12C5 reacted weakly with 5B4. These observations demonstrate that an epitope reacting with 12C5 is more abundant in some myofibrils than in others within the same cell. Three categories of myofibrils can be identified by their relative proportions of embryonic and neonatal forms of myosin: in nearly all fibrils, a neonatal isoform predominates; in a minority population, embryonic and neonatal isoforms are both abundant; and in a few fibrils, an embryonic isoform predominates. It is concluded that there are distinct populations of myofibrils in which specific isoforms are segregated within an individual cell. PMID- 2307703 TI - Dictyostelium discoideum plasma membranes contain an actin-nucleating activity that requires ponticulin, an integral membrane glycoprotein. AB - In previous equilibrium binding studies, Dictyostelium discoideum plasma membranes have been shown to bind actin and to recruit actin into filaments at the membrane surface. However, little is known about the kinetic pathway(s) through which actin assembles at these, or other, membranes. We have used actin fluorescently labeled with N-(1-pyrenyl)iodoacetamide to examine the kinetics of actin assembly in the presence of D. discoideum plasma membranes. We find that these membranes increase the rate of actin polymerization. The rate of membrane mediated actin polymerization is linearly dependent on membrane protein concentrations up to 20 micrograms/ml. Nucleation (the association of activated actin monomers into oligomers) appears to be the primary step of polymerization that is accelerated. A sole effect on the initial salt-induced actin conformational change (activation) is ruled out because membranes accelerate the polymerization of pre-activated actin as well as actin activated in the presence of membranes. Elongation of preexisting filaments also is not the major step of polymerization facilitated by membranes since membranes stripped of all peripheral components, including actin, increase the rate of actin assembly to about the same extent as do membranes containing small amounts of endogenous actin. Acceleration of the nucleation step by membranes also is supported by an analysis of the dependence of polymerization lag time on actin concentration. The barbed ends of membrane-induced actin nuclei are not obstructed by the membranes because the barbed end blocking agent, cytochalasin D, reduces the rate of membrane-mediated actin nucleation. Similarly, the pointed ends of the nuclei are not blocked by membranes since the depolymerization rate of gelsolin-capped actin is unchanged in the presence of membranes. These results are consistent with previous observations of lateral interactions between membranes and actin filaments. These results also are consistent with two predictions from a model based on equilibrium binding studies; i.e., that plasma membranes should nucleate actin assembly and that membrane-bound actin nuclei should have both ends free (Schwartz, M. A., and E. J. Luna. 1988. J. Cell Biol. 107:201-209). Integral membrane proteins mediate the actin nucleation activity because activity is eliminated by heat denaturation, treatment with reducing agents, or proteolysis of membranes. Activity also is abolished by solubilization with octylglucoside but is reconstituted upon removal or dilution of the detergent. Ponticulin, the major actin-binding protein in plasma membranes, appears to be necessary for nucleation activity since activity is not reconstituted from detergent extracts depleted of ponticulin. PMID- 2307705 TI - Nucleus-specific translation and assembly of acetylcholinesterase in multinucleated muscle cells. AB - Multinucleated skeletal muscle fibers synthesize cell surface and secreted oligomeric forms of acetylcholinesterase (AChE) that accumulate at specialized locations on the cell surface, such as sites of nerve-muscle contact. Using allelic variants of the AChE polypeptide chains as genetic markers, we show that nuclei homozygous for either the alpha or beta alleles residing in chimeric myotubes preferentially translate their AChE mRNAs on their respective ERs. These results indicate that the events of transcription, translation, and assembly of this membrane protein are compartmentalized into nuclear domains in multinucleated cells, and provide the structural basis for the possible localized expression and regulation of synaptic components at the neuromuscular junctions of vertebrate skeletal muscle fibers. PMID- 2307706 TI - Sorting during transport to the surface of PC12 cells: divergence of synaptic vesicle and secretory granule proteins. AB - PC12 cells, a cell line derived from a rat pheochromocytoma, have both regulated and constitutive secretory pathways. Regulated secretion occurs via large dense core granules, which are related to chromaffin granules and are abundant in these cells. In addition, PC12 cells also contain small electron-lucent vesicles, whose numbers increase in response to nerve growth factor and which may be related to cholinergic synaptic vesicles. These could characterize a second regulated secretory pathway. We have investigated the trafficking of protein markers for both these organelles. We have purified and characterized the large dense core granules from these cells using sequential velocity and equilibrium gradients. We demonstrate the copurification of the major PC12 soluble regulated secretory protein (secretogranin II) with this organelle. As a marker for the synaptic vesicle-like organelles in this system, we have used the integral membrane glycoprotein p38 or synaptophysin. We show that the p38-enriched fraction of PC12 cells comigrates with rat brain synaptic vesicles on an equilibrium gradient. We also demonstrate that p38 purifies away from the dense core granules; less than 5% of this protein is found in our dense granule fraction. Finally we show that p38 does not pass through the dense granule fraction in pulse-chase experiments. These results rule out the possibility of p38 reaching the small clear vesicles via mature dense granules and imply that these cells may have two independently derived regulated pathways. PMID- 2307707 TI - RGD-independent cell adhesion to the carboxy-terminal heparin-binding fragment of fibronectin involves heparin-dependent and -independent activities. AB - Cell adhesion to extracellular matrix components such as fibronectin has a complex basis, involving multiple determinants on the molecule that react with discrete cell surface macromolecules. Our previous results have demonstrated that normal and transformed cells adhere and spread on a 33-kD heparin binding fragment that originates from the carboxy-terminal end of particular isoforms (A chains) of human fibronectin. This fragment promotes melanoma adhesion and spreading in an arginyl-glycyl-aspartyl-serine (RGDS) independent manner, suggesting that cell adhesion to this region of fibronectin is independent of the typical RGD/integrin-mediated binding. Two synthetic peptides from this region of fibronectin were recently identified that bound [3H]heparin in a solid-phase assay and promoted the adhesion and spreading of melanoma cells (McCarthy, J. B., M. K. Chelberg, D. J. Mickelson, and L. T. Furcht. 1988. Biochemistry. 27:1380 1388). The current studies further define the cell adhesion and heparin binding properties of one of these synthetic peptides. This peptide, termed peptide I, has the sequence YEKPGSP-PREVVPRPRPGV and represents residues 1906-1924 of human plasma fibronectin. In addition to promoting RGD-independent melanoma adhesion and spreading in a concentration-dependent manner, this peptide significantly inhibited cell adhesion to the 33-kD fragment or intact fibronectin. Polyclonal antibodies generated against peptide I also significantly inhibited cell adhesion to the peptide, to the 33-kD fragment, but had minimal effect on melanoma adhesion to fibronectin. Anti-peptide I antibodies also partially inhibited [3H]heparin binding to fibronectin, suggesting that peptide I represents a major heparin binding domain on the intact molecule. The cell adhesion activity of another peptide from the 33-kD fragment, termed CS1 (Humphries, M. J., A. Komoriya, S. K. Akiyama, K. Olden, and K. M. Yamada. 1987. J. Biol. Chem., 262:6886-6892) was contrasted with peptide I. Whereas both peptides promoted RGD independent cell adhesion, peptide CS1 failed to bind heparin, and exogenous peptide CS1 failed to inhibit peptide I-mediated cell adhesion. The results demonstrate a role for distinct heparin-dependent and -independent cell adhesion determinants on the 33-kD fragment, neither of which are related to the RGD dependent integrin interaction with fibronectin. PMID- 2307708 TI - Binding properties of detergent-solubilized NCAM. AB - An assay has been designed for the identification of NCAM-binding proteins present in an NP-40 detergent extract of brain membranes. This method, which is capable of analyzing both heterophilic and homophilic interactions, uses species specific antibodies against NCAM in combination with radioiodination, so that after unlabeled chicken and iodinated frog brain membrane proteins were allowed to interact, the chicken NCAM could be specifically isolated by immunoaffinity adsorption. The radiolabeled frog proteins coisolated with chicken NCAM were then characterized by one- and two-dimensional gel electrophoresis in combination with immunoblotting. The only detectable NCAM-binding proteins were identified as the 140- and 180-kD forms of NCAM. The presence and absence of polysialic acid on NCAM did not change the amount or nature of the frog proteins immunopurified under these conditions. As an alternative for detecting heterophilic ligands, a simplified immunoprecipitation method was employed using either iodine or sulfate radiolabels. Again under these conditions only NCAM was detected. These results are consistent with the hypothesis that the major binding protein for NCAM is NCAM itself, and suggest that differences in polysialic acid content do not directly alter the properties of NCAM's homophilic binding site. PMID- 2307709 TI - Terminal short arm domains of basement membrane laminin are critical for its self assembly. AB - Laminin self-assembles into large polymers by a cooperative two-step calcium dependent mechanism (Yurchenco, P. D., E. C. Tsilibary, A. S. Charonis, and H. Furthmayr. 1985. J. Biol. Chem. 260:7636-7644). The domain specificity of this process was investigated using defined proteolytically generated fragments corresponding to the NH2-terminal globule and adjacent stem of the short arm of the B1 chain (E4), a complex of the two short arms of the A and B2 chains attached to the proximal stem of a third short arm (E1'), a similar complex lacking the globular domains (P1'), and the distal half of the long arm attached to the adjacent portion of the large globule (E8). Polymerization, followed by an increase of turbidity at 360 nm in neutral isotonic TBS containing CaCl2 at 35 degrees C, was quantitatively inhibited in a concentration-dependent manner with laminin fragments E4 and E1' but not with fragments E8 and P1'. Affinity retardation chromatography was used for further characterization of the binding of laminin domains. The migration of fragment E4, but not of fragments E8 and P1', was retarded in a temperature- and calcium-dependent fashion on a laminin affinity column but not on a similar BSA column. These data are evidence that laminin fragments E4 and E1' possess essential terminal binding domains for the self-aggregation of laminin, while fragments E8 and P1' do not. Furthermore, the individual domain-specific interactions that contribute to assembly are calcium dependent and of low affinity. PMID- 2307712 TI - Purification of transforming growth factor type e. AB - Transforming growth factor type e (TGFe) is a heat- and acid-stable polypeptide with an apparent molecular weight of 22,000, which stimulates the proliferation of certain epithelial and mesenchymal cells in monolayer and soft agar. TGFe has been purified to homogeneity. Initial acid-ethanol extraction of bovine kidney was followed by batch ion-exchange chromatography utilizing Bio Rex 70 resin. The activity eluted from the Bio Rex 70 resin was concentrated and diafiltered using an Amicon concentrator equipped with an S1Y10 spiral membrane, then was further purified by Bio-Gel P-60 molecular sieve chromatography. Active fractions from molecular sieve chromatography were pooled and purified by heparin-Sepharose affinity chromatography, followed by reverse-phase high-performance liquid chromatography using a microbore C-8 column. The final purification step involved electro-elution of TGFe separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Purity of TGFe was assessed to be greater than 90%. PMID- 2307710 TI - Retroviral expression of alternatively spliced forms of rat fibronectin. AB - We describe the construction in retroviral vectors and the expression of recombinant rat fibronectin (FN) cDNAs corresponding with the various alternatively spliced forms of FN. In NIH 3T3 cells, the exogenous rat FN subunits are efficiently secreted as heterodimers with endogenous mouse subunits. In contrast, in lymphoid WEHI231 cells, there is no endogenous FN synthesis and the recombinant FNs are secreted and can be purified as homogeneous proteins. We show that the purified recombinant FNs are biochemically and biologically functional. In basic assays for adhesion, spreading, cytoskeletal organization, and migration using various established adherent cell lines, different forms of FNs containing the different alternatively spliced segments show no marked differences in activity. We have used these recombinant FNs to investigate three systems in which earlier results had suggested potential differences between different forms of FN. First, all forms tested appear equally active in restoring normal morphology to a transformed cell line. Second, we detect minor differences in their ability to assemble into preexisting extracellular matrices. Finally, we report that only those forms of FN that contain the V segment will promote the spreading of a lymphoid cell line indicating that this segment confers additional biological functions for some cell types, a result that confirms and extends earlier data. These homogeneous, biologically active recombinant FNs will allow further studies of the role of the alternatively spliced segments of FN. PMID- 2307711 TI - Type IV collagen mRNA accumulates in the mesenchymal compartment at early stages of murine developing intestine. AB - The expression of type IV collagen mRNA during mouse intestinal morphogenesis was examined by in situ hybridization using a cDNA probe corresponding to mRNA for alpha 1 (IV) chain. Type IV collagen mRNA is detected in the embryonic mesenchymal cells at early stages of development (12 d of gestation). A segregation of mesenchymal cells expressing high levels of type IV collagen mRNA in close vicinity of the epithelium occurs just before villus formation. During villus outgrowth, type IV collagen mRNA, still confined to mesenchyme-derived tissues, is progressively restricted to the mucosal connective tissue (the lamina propria) and to a lesser extent to the muscular layers. In the adult, the amount of messenger is quite low as compared to the level found in the developing intestine and the in situ hybridization signal, indistinguishable from the background, is uniform throughout the whole intestinal wall. At all developmental stages no detectable specific hybridization signal is virtually observed over the epithelium cell layer. These results show that high amounts of the type IV collagen messenger are detected during phases of intensive morphogenetic events. Furthermore, they reinforce the notion already gained previously (Simon-Assmann et al. 1988) that the mesenchymal compartment is the principal endogenous source of type IV collagen. They also indicate that the continuous migration of epithelial cells along the basement membrane of intestinal villi in the mature organ is not accompanied by a significant remodeling of the collagen IV network. PMID- 2307713 TI - Inhibition of epidermal growth factor receptor activity by retinoic acid in glioma cells. AB - The growth inhibitory effects of exogenously added retinoic acid (RA) on various cultured human glioma cells was observed to be heterogenous, with an ID50 ranging from 10(-7) M to no response. The protein tyrosine kinase activity of epidermal growth factor receptor (EGF-receptor) appeared to parallel the cell's growth responsiveness to RA. Cells sensitive to RA-induced growth inhibition exhibited a dose-dependent decrease in EGF-receptor activity, whereas RA-resistant cells showed no alterations in EGF-receptor protein tyrosine kinase activity or expression. The modulation of EGF-receptor by RA was further examined with RA sensitive (LG) and -resistant (NG-1) cell lines. Both cell lines were approximately equal in their ability to bind and internalize epidermal growth factor in the presence or absence of RA. Several independent assays suggested that the inhibition of EGF-receptor activity was independent of protein kinase C modulation as mediated by phorbol myristate acetate. However, alterations in associated glycoconjugates of EGF-receptor were observed among the sensitive cells but not the resistant cells. These results suggest RA-induced growth inhibition in sensitive cells may arise, at least in part, through alterations in EGF-receptor and structure. PMID- 2307714 TI - Androgenic control of N-acetyltransferase activity in the harderian glands of the Syrian hamster is mediated by 5 alpha-dihydrotestosterone. AB - N-acetyltransferase (NAT) activity in the Harderian glands of intact and gonadectomized male and female Syrian hamsters was evaluated. The exogenous administration of 5 alpha-dihydrotestosterone (DHT) to castrated males and intact females produced an increase in NAT values, which reached the values present in the glands of intact males. The administration of a 5 alpha-reductase inhibitor to intact males led to a decrease in NAT activity, suggesting that testosterone is converted in DHT within the glands. It is concluded that NAT activity in the Syrian hamster Harderian glands is under androgenic control, the active steroid being DHT. PMID- 2307715 TI - Separation and determination of the ingredients of a cold medicine by micellar electrokinetic chromatography with bile salts. AB - The separation of fourteen active ingredients used in a cold medicine was investigated by micellar electrokinetic chromatography (EKC) employing bile salts. Basic drugs were also successfully separated by micellar EKC using bile salts with high theoretical plate numbers (2.0 x 10(5)-3.5 x 10(5)) within a relatively short time (ca. 20 min). The separation of these solutes by micellar EKC was not successful using sodium dodecyl sulphate. The effects of micellar concentration, pH and organic modifier content on migration times and selectivity were investigated. This technique was also applied to the determination of several active ingredients combined in commercial preparations by an internal standard method. PMID- 2307716 TI - Computerized capillary gas chromatographic analysis of hydrocarbon mixtures in workplace air. AB - The quantitative composition of white spirit vapours in workplace air may differ considerably from the solvent being used, although all components are the same. By calculating the hygienic effect from the threshold limit value (NGV) of each component, a more reliable estimate is obtained of the occupational hazard than by using the NGV for white spirit. In this method the analyses were performed by on-column injection onto a temperature-programmed capillary column. Retention indices based on n-paraffins and isooctane were calculated using spline functions. Index tables were established for different hydrocarbon mixtures. The validity of the retention indices was found to be satisfactory, depending on the stability of the column and the possibility of optimizing the indices when replacing one column by another of the same type and dimensions. Comparisons were made with alternative methods for determining the concentration of white spirit vapours in air samples. A polar column was used to check the total content of aromatics. PMID- 2307717 TI - Association of logistic and Poisson models of infection with some physical characteristics of a single component plant virus. AB - A logistic model was recently formulated to describe the relationship between concentration of a single component plant virus and infections produced by inoculation to a local lesion host. In this paper the logistic is combined with a Poisson model. The logistic makes accurate fitting possible for a variety of infection-dilution series; and the Poisson acts as a base line, indicating whether lesion numbers are compatible with the hypothesis that random infection of similar infection sites has occurred. A logarithmic form of the logistic equation gives a straight line with negative slope (logit slope) which is useful in characterizing dilution series to which the logistic is fitted. A modified Poisson equation can also be fitted to a range of dilution series; it provides an independent estimate of slope for curves not widely divergent from the standard Poisson. Models have also been developed to define the limits of concentration within which single virions are likely to be randomly dispersed in inoculum without immediate contact with other virions, and are therefore more likely to enter inoculated tissue independently and cause random infections. Models are formulated for aggregation of tobacco mosaic virus in monolayers, crystals, and lenticular aggregates. Published and unpublished data are fitted and analyzed using some of these models. PMID- 2307718 TI - An automatic modified polymerase chain reaction procedure for hepatitis B virus DNA detection. AB - In order to perform an efficient and reproducible diagnostic test for hepatitis B virus (HBV) infection using the polymerase chain reaction (PCR), sixteen primer couples specific for the HBV genome were selected. Primers 15-31 nucleotides in length containing between 31-73% GC permitted amplification of fragments corresponding to the whole HBV genome. The specificity and efficiency of PCR amplification were studied in detail using DNA extracted from either a viral particle preparation or from the liver of a patient with chronic active hepatitis. Three primer couples in the X, C and PreS regions, i.e. MD24/MD26, MD27/MD31 and MD19/MD18, respectively, gave satisfactory results and performed efficiently under highly stringent hybridization conditions. A modified PCR procedure was then developed using only two thermal steps with a temperature shift of 16 degrees C. This simple method was as efficient as conventional PCR and permitted detection of a single HBV DNA molecule with the X region specific primer couple. The automatization of this PCR-based procedure permitted 40 amplification cycles in 105 min. PMID- 2307719 TI - Comparison of neuraminidases of the same subtype but from different species using a new method of titration. AB - Neuraminidase is one of the two surface glycoproteins of influenza virions. In order to compare neuraminidases of the same subtype but isolated from different species (man, birds, pig), a new and simple method was adapted and optimized using peanut hemagglutinin. Results were very similar to those obtained with the classical method recommended by the WHO, using fetuin as a substrate. The technique was used to examine the relationship between animal and human neuraminidases belonging to serotypes N1 and N2. The results confirm the possible role of ducks as a reservoir for influenza viruses and the eventuality of interspecific exchanges. PMID- 2307720 TI - The growing spectrum of HIV-related endocrine abnormalities. PMID- 2307721 TI - Serum immunoreactive inhibin levels before and after luteectomy in the cynomolgus monkey (Macaca fascicularis). AB - Whereas studies in women have demonstrated that serum immunoreactive inhibin concentrations peak during the luteal phase of the menstrual cycle and that the corpus luteum (CL) encodes mRNA for the inhibin subunits, a clear link between the presence of the CL and circulating inhibin has not been established in primates. Therefore, we measured serum immunoreactive inhibin levels in monkeys before and after luteectomy as well as immunoreactive inhibin concentrations and mRNA encoding the alpha-inhibin subunit in luteal tissue. Monkeys were assigned to one of four groups depending on which day of the luteal phase luteectomy was performed: group A, days 4-5; group B, days 7-8; group C, days 9-10; and group D, days 11-12 (the day after the estrogen surge = day 1 of the luteal phase). Daily blood samples were obtained for 3 days before luteectomy, immediately before surgery, and for 2 days after luteectomy. Immunoreactive inhibin concentrations were measured with a double antibody RIA using an antiserum to bovine 31-kDa inhibin, bovine 31-kDa inhibin for iodination, and a human follicular fluid inhibin preparation as standard. Total RNA was isolated from luteal tissue and transferred by Northern blot onto a Zeta-probe membrane. The probe used for hybridization was the PstI/NcoI restriction enzyme fragment (381 basepairs) of alpha-inhibin DNA generated from a human ovarian cDNA library. Serum inhibin concentrations decreased (P less than 0.05) 24 h after removal of the corpus luteum in each of the four groups studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307722 TI - Certain large forms of circulating immunoreactive human growth hormone are in fact immunoglobulins. AB - To explain frequent discordances between serum GH levels and clinical manifestation of acromegaly, we investigated the possibility that certain immunoglobulins G (IgGs) might be responsible for the displacement of [125I]human (h) GH in the hGH RIA. We incubated dilute sera from seven active acromegalics (basal immunoreactive hGH, 22-313 micrograms/L) with rat adipocyte plasma membranes adsorbed on polystyrene plates. IgGs that bound to GH receptor sites in the absence and presence of 250 nM hGH (for nonspecific binding) were detected using anti-hIgG (Fc-specific) antibody conjugated with alkaline phosphatase. In this system two of the seven sera studied tested positive for IgGs against GH binding sites (serum 4 in 1:400 dilution, and serum 7 in 1:10 dilution). We studied further the serum with the highest titer. On Sephadex G-100, most of the GH-like immunoreactivity (assayed by RIA) present in serum 4 coeluted with IgGs (assayed by immunodiffusion) as a high mol wt (greater than or equal to 150 kDa) component. To confirm its IgG nature, this material was then adsorbed on protein A-Sepharose and eluted with 0.1 M sodium citrate, pH 3.0. The protein-A-purified IgGs from serum 4 bound specifically to GH receptor sites in adipocyte membranes and displaced [125I]hGH in the hGH RIA. In contrast, IgGs purified from another acromegalic patient (313 micrograms/L hGH) repeatedly tested negative in the membrane binding assay and hGH RIA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307723 TI - Retinoic acid inhibition of hyaluronate synthesis in cultured human skin fibroblasts. AB - The effects of all-trans retinoic acid on glycosaminoglycan (GAG) accumulation were determined in cultured primary human skin fibroblasts. Confluent cultures treated with retinoic acid accumulated less [3H]GAG than those without the compound, an effect with an apparent threshold of 10 nM which was dose dependent in the concentration range tested (0-10 microM). At 10 microM, the inhibition was 54%. Greater than 80% of the labeled macromolecular material was streptomyces hyaluronidase digestible in cultures labeled with [3H]acetate. The incorporation of H2[35S]O4 into chondroitin sulfate and dermatan sulfate was unaffected, as was total protein synthesis. Retinol also inhibited accumulation of [3H]GAG, but was far less potent. T3 and dexamethasone can inhibit [3H]hyaluronate synthesis. When retinoic acid was added to cultures treated with either of these hormones at concentrations that maximally inhibit [3H] GAG accumulation, there was a further decrease in the rate of macromolecular accumulation. The retinoic acid effect evolved over 24-48 h after addition to the culture medium. A pulse-chase study failed to demonstrate any effect on [3H]GAG degradation. PMID- 2307724 TI - A second, lower affinity growth hormone-binding protein in human plasma. AB - In our previous description of the circulating GH-binding protein (GH-BP) we observed, in addition to the main GH-BP complex, a second macromolecular component designated peak I during gel filtration of [125I]GH-plasma mixtures. This component was not further characterized because of its small magnitude, seeming nonsaturability, and suspected artifactual nature. We have now characterized peak I as the complex of a low affinity BP with GH. To gain a better knowledge of the nature of peak I, whole plasma or plasma fractions containing isolated peak I-BP (ammonium sulfate precipitated or prepared by gel filtration of plasma) were incubated with monomeric [125I]GH and varying concentrations of unlabeled GH. The mixtures were then analyzed by Sephadex G-100 chromatography to separate free from protein-bound GH. Peak I-associated radioactivity was saturable at high concentrations of human GH, but not with animal GHs. Saturation/Scatchard analysis yielded an association constant of 10(5) M-1 and a maximum binding capacity of 15 mg/L plasma. Chemically cross linked complexes of [125I]GH with isolated peak I BP were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, and two dimensional electrophoresis. These experiments yielded a mol wt of 124 kD and a pI of 7 for the cross-linked complex. This is in contradistinction to the previously reported high affinity GH-BP complex, which when cross-linked has a mol wt of 76 kD and a pI of 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307726 TI - Dual energy radiography versus quantitative computer tomography for the diagnosis of osteoporosis. AB - In this study we compared dual energy radiography (DER), a new, highly precise x ray densitometric technique recently devised for measurements of vertebral mineral density and quantitative computer tomography (QCT), a densitometric technique that selectively measures the trabecular compartment of the vertebra. DER and QCT measurements were obtained in 56 healthy (H) and 48 fractured osteoporotic (OP) women using a Hologic QDR 1000 bone densitometer and a GE 9800 scanner, respectively. DER was significantly correlated with QCT in both the H (r = 0.75; P less than 0.0001) and the OP subjects (r = 0.58; P less than 0.0001). DER decreased significantly with age in the H (P less than 0.05), but not in the OP women, whereas QCT was related to age in both the H (P less than 0.0001) and the OP subjects (P less than 0.01). The rate of bone loss with age was also higher with QCT than with DER in both normal and osteoporotic women. The difference in bone density between the H and the OP subjects was larger (P less than 0.05) with QCT than with DER. Receiver operating characteristic analysis revealed that QCT was a better predictor of vertebral fractures than DER. A larger percentage of OP subjects were 2 SD or more below the normal predicted value with QCT (41%) than with DER (29%). Furthermore, the slopes of the regressions of bone density with age for normal and osteoporotic women were significantly different (P less than 0.05) with QCT but not with DER. These findings are consistent with a disproportionate loss of trabecular bone with age in osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307725 TI - Human fetal adrenal definitive and fetal zone metabolism of pregnenolone and corticosterone: alternate biosynthetic pathways and absence of detectable aldosterone synthesis. AB - In the rhesus monkey and ovine fetus in utero, aldosterone concentrations do not rise in response to surgical stress, ACTH, or angiotensin-II, all of which are secretagogues for this mineralocorticoid in the adult. To assess the mechanism of this phenomenon in the human fetus, metabolism of pregnenolone and corticosterone by second trimester human fetal adrenal definitive zone and fetal zone tissue was studied. After incubation of fresh tissue with trace amounts of [3H]pregnenolone or [3H]corticosterone, the products of metabolism were separated using high performance liquid chromatography and quantified. The delta 5-3 beta hydroxysteroids 17-hydroxypregnenolone and dehydroepiandrosterone and their sulfates comprised 85-90% of metabolized pregnenolone. In the fetal zone, cortisol was the predominant secreted delta 4-3-ketosteroid, accounting for 6-8% of the metabolized pregnenolone. In the definitive zone, progesterone and corticosterone were the predominant secreted delta 4-3-ketosteroids, each accounting for about 2% of the metabolized pregnenolone. 11-Dehydrocorticosterone and sulfates were the only metabolites detected after incubation of fetal adrenal tissue with corticosterone. 11-Dehydrocorticosterone accounted for more than 80% of the metabolized corticosterone in the definitive zone and 50% in the fetal zone. Incubations with secretagogues or antioxidants (10 nmol/L ACTH, 10 nmol/L angiotensin-II, 21 mmol/L potassium, 100 mmol/L dimethylsulfoxide, 5 mumol/L metyrapone, or 100 mumol/L butylated hydroxyanisole) did not change the pattern or extent of precursor metabolism. No aldosterone, 18-hydroxycorticosterone, or 18-hydroxydeoxycorticosterone was detected in baseline or stimulated incubations of human fetal tissue. In contrast, adult human zona glomerulosa metabolized corticosterone to aldosterone, 18-hydroxycorticosterone, and 11 dehydrocorticosterone under similar conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307727 TI - Somatomedin-C, physical fitness, and bone density. AB - Somatomedin-C (Sm-C) or insulin-like growth factor-I, GH and physical fitness decline with age. Physical fitness and muscle strength are important determinants of bone density, and the age-related decline in bone density may be related in part to a decline in fitness and muscle strength. Also, Sm-C has been shown to stimulate osteoblasts in vitro and may effect skeletal muscle mass. We postulated that the age-related decline in GH and Sm-C levels may be related to an age related decline in physical fitness and/or muscle strength, and the effect of physical fitness and muscle strength on bone may be mediated by Sm-C. We, therefore, examined the relationship between circulating GH and Sm-C levels and physical fitness, as determined by predicted maximal oxygen uptake (VO2max) in 134 normal women, 34 of whom were postmenopausal. In a subgroup of 62 women overall muscle strength was estimated as the sum of the Z-sores for biceps, quadriceps, and grip strength. Overall muscle strength correlated with GH levels (r = 0.28; P less than 0.02), but not with Sm-C levels. There was a significant positive relationship between plasma Sm-C levels and VO2max in all women (r = 0.47; P less than 0.001) and in the postmenopausal group alone (r = 0.05; P less than 0.01). Although there was a significant negative relationship between Sm-C and age (r = -0.36; P = 0.001), VO2max was a better independent predictor than age (r = 0.47; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307728 TI - Autosomal dominant transmission of autoantibodies to thyroglobulin and thyroid peroxidase. AB - The inheritance of autoantibodies to thyroglobulin and thyroid peroxidase (thyroid microsomal antigen) has been reevaluated with newly developed ultrasensitive assays that depend on the direct interaction between antibody and radiolabeled antigen. In a study of 16 families with autoimmune thyroid disease, autoantibodies to thyroid peroxidase (TPO) were found to be inherited as a dominant Mendelian trait in females with reduced penetrance in males. Similar results were obtained with thyroglobulin (Tg) autoantibodies. Genetic linkage analysis of the loci for TPO and Tg autoantibodies with 28 polymorphic serological markers (including HLA and Gm allotypes) was carried out in 9 families. LOD scores for some serological markers (such as Gm) were uninformative, but linkage with other markers, notably the HLA antigens -A, B, DR, -DQ, and BF on chromosome 6, could be excluded. Further studies using a comprehensive panel of gene probes to analyze DNA from families with autoimmune thyroid disease should permit the localization of the gene cluster responsible for regulating the ability to produce autoantibodies to TPO and Tg in man. PMID- 2307729 TI - Studies with purified human thyroid peroxidase and thyroid microsomal autoantibodies. AB - We have isolated highly purified thyroid peroxidase (TPO) from human thyroid tissue to study further the relationship between TPO and the thyroid microsomal antigen that elicits the production of microsomal autoantibodies in patients with autoimmune thyroid disease. Serum samples were obtained from 24 patients with suspected autoimmune thyroid disease, and from 7 normal subjects. Microsomal autoantibodies in the patient sera, as determined by the microsomal hemagglutination assay (MCHA), varied between 1:100 and 1:102,400. Antithyroglobulin antibodies, however, were very low (less than 1:100). Binding of serum autoantibodies to purified human TPO, as determined by enzyme-linked immunosorbent assay, correlated fairly well with MCHA titers (r = 0.72; P less than 0.001). An immunoblot procedure was developed to study the binding of serum antibodies to the major active fragment of TPO (93 kDa), after sodium dodecyl sulfate-polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. Binding under both conditions correlated very well with MCHA titers (r = 0.80-0.84; P less than 0.001). Studies were performed to determine the inhibitory effect of patient serum on the enzymatic activity of purified human TPO. A marked inhibitory effect on guaiacol activity was observed when TPO was preincubated with as little as 10 microL high titer serum. There was a significant correlation (r = 0.47; P less than 0.01) between MCHA titer and inhibitory effect. The addition of 2 micrograms purified human TPO completely or almost completely inhibited the binding of serum antibodies to thyroid microsomes (enzyme-linked immunosorbent assay) in 10 of 11 patient sera with high MCHA titers (1:25,600 or greater). PMID- 2307730 TI - Negative correlation between the change in bone mineral density and serum osteocalcin in patients with hyperthyroidism. AB - To assess the changes in bone mineral density and osteoblastic activity in patients with hyperthyroidism and to investigate the relationship between those changes, we measured bone mineral density and serum osteocalcin in 109 patients with Graves' disease, comprising 75 untreated patients and 34 patients under treatment, and 200 normal controls. The degree of change in bone mineral density was quantified with Z transformation, in which we used means and SDs of bone mineral densities obtained in the process of age- and sex-matched 1:1 pairing developed by ourselves. Bone mineral density was low in female patients with hyperthyroidism in the spine, femur neck, trochanter, and Ward's triangle, but was not low in male patients. Serum osteocalcin was elevated in patients with untreated Graves' disease and correlated negatively with the Z values of bone mineral densities of the spine, femur neck, and trochanter. In conclusion, indices of osteoblastic activity were elevated in patients with hyperthyroidism, probably secondary to a thyroid hormone-induced increase in bone resorption which resulted in reduced bone mineral density. Quantification of the change in bone mineral density by using the parameters derived in the process of age- and sex matched pairing seems to be an efficient method for statistical analyses. PMID- 2307731 TI - Erythrocyte zinc concentration in patients with subacute thyroiditis. AB - We have recently reported that red blood cell (RBC) zinc (Zn) in patients with hyperthyroidism reflects a patient's integrated thyroid hormone level over the previous few months. In the present paper RBC Zn concentrations were measured in 10 patients with subacute thyroiditis whose total plasma T4 and T3 levels were elevated. The values were compared with those obtained in 10 patients with untreated Graves' disease, whose plasma T4 concentrations were elevated to the same level as in the former group. The RBC Zn concentration was normal in 9 of 10 patients with subacute thyroiditis, but was depressed in all patients with Graves' disease. The mean (+/- SE) RBC Zn in patients with subacute thyroiditis was 162 +/- 9 mumol/L, significantly (P less than 0.001) higher than that in Graves' disease (87 +/- 5 mumol/L). During prednisolone treatment the RBC Zn in patients with subacute thyroiditis remained at the normal level and did not change significantly, although it was slightly decreased at 2 and 4 weeks of treatment. On the other hand, the RBC Zn in patients with Graves' disease was significantly increased at 8 weeks of treatment and reached the normal range in 12 weeks. These results suggest that elevation of plasma thyroid hormone concentrations in patients with subacute thyroiditis is transient and does not cause any significant change in the RBC Zn concentration. PMID- 2307732 TI - Testosterone replacement therapy and sleep-related erections in hypogonadal men. AB - Hypogonadal men usually have diminished libido and erectile dysfunction, and testosterone replacement therapy in these men increases sexual activity, erotic thoughts, and self-reported nocturnal erections. The polygraphic assessment of nocturnal penile tumescence (NPT) provides an objective index of erectile capability and is useful for differentiating psychogenic from organic erectile dysfunction. In this study we evaluated NPT in six hypogonadal adult men during and after termination of androgen therapy. Multinight sleep studies were conducted within 1 week and 7-8 weeks after each man received 20 mg testosterone cypionate, im. The mean serum testosterone level 4-7 days after testosterone injection was 35.9 +/- 3.4 (+/- SE) nmol/L, and it fell to 2.3 +/- 0.9 nmol/L after 7-8 weeks. Significant declines (P less than 0.05) in the number of NPT episodes (3.7 to 2.0), maximum penile circumference increase (24 to 13 mm), and total tumescence time (107 to 55 min) accompanied the fall in the serum testosterone level. No androgen-related changes in the amount or integrity of rapid eye movement sleep were found. Finally, the mean penile rigidity (buckling pressure) decreased from 770 +/- 98 to 590 +/- 81 g (P less than 0.05). Comparison of these results to those in normal men revealed that none of these men met all diagnostic criteria for organic impotence, even 7-8 weeks after discontinuation of testosterone administration. While men with androgen deficiency may have normal NPT, sleep-related erections increase in response to testosterone administration. PMID- 2307734 TI - Evidence for an intracerebral action of phenylalanine in stimulation of prolactin secretion: interaction of large neutral amino acids. AB - Phenylalanine stimulates PRL secretion when given orally or iv to normal individuals. To differentiate between hypothalamic and pituitary sites of action, we examined the effects of concurrent infusion of valine on the PRL response to iv phenylalanine in eight normal men. Since large neutral amino acids share the same high affinity blood-brain barrier transport system, entry of phenylalanine into the brain will be diminished by the simultaneous presence of high serum concentrations of valine; the pituitary, lying outside the blood-brain barrier, is not subject to these competitive effects. Valine significantly blunted the PRL response to phenylalanine, supporting an effect of phenylalanine within the blood brain barrier to stimulate PRL release. PMID- 2307733 TI - T-lymphoblast cell lines from Laron dwarfs augment basal colony formation in response to extremely high concentrations of growth hormone. AB - The clinical entity of Laron dwarfism is characterized by resistance to both endogenous and exogenous GH and may be due to a deficiency or absence of functional GH receptors. We previously showed that two types of hematopoietic cells derived from these patients are resistant to the in vitro growth-promoting action of GH at concentrations below 500 micrograms/L. In the current study we found that Laron T-cell lines had a mean peak augmentation of basal colony formation of 22 +/- 3.4% above baseline in response to a GH concentration of 10,000 micrograms/L. Since cloned cDNAs for human and rabbit GH receptors and rat PRL receptors show a high degree of sequence homology, we undertook studies of PRL action in cells from patients with Laron dwarfism to determine if the Laron defect was also associated with PRL unresponsiveness. Quantitating the augmentation of colony formation by T-lymphoblast cell lines established from three Laron dwarfs, we found normal responsiveness to PRL at concentrations of 25 10,000 micrograms/L. It is, thus, possible that the responsiveness of Laron T cell lines to very high concentrations of GH could be mediated through an intact PRL (or other lactogenic) receptor based on the known affinity of GH for these receptors in other systems. These data suggest that cells from patients with Laron dwarfism have normal in vitro responsiveness to PRL and that the defect in Laron dwarfism appears to be specific to the GH receptor-effector pathway. It remains to be determined whether intact alternative lactogenic receptor mechanisms subserve any clinical effects of GH in patients with Laron dwarfism. PMID- 2307735 TI - Carbamazepine in the prophylaxis of mood disorders. AB - Alternatives to lithium are desirable in the prophylaxis of affective disorders, especially in patients who are intolerant of or do not respond to that drug. In the past few years the anticonvulsant carbamazepine has been in the foreground of discussion. Twenty-four patients with affective disorders (17 unipolar depressed, six bipolar, and one unipolar manic) were included in a comparative trial of lithium and carbamazepine; 12 had been pretreated with lithium without a satisfactory effect. All patients received carbamazepine (four received it in combination with lithium) over a mean time span of 20.2 months. Eighty percent of the patients improved with carbamazepine treatment. Side effects were infrequent. PMID- 2307736 TI - Lorazepam as an adjunct in the treatment of catatonic states: an open clinical trial. PMID- 2307737 TI - The aphrodisiac effect of fenfluramine: two case reports of a possible side effect to the use of fenfluramine in the treatment of bulimia. PMID- 2307738 TI - An open trial of glycine as an adjunct to neuroleptics in chronic treatment refractory schizophrenics. PMID- 2307739 TI - Electroconvulsive therapy complicated by insecticide ingestion. PMID- 2307740 TI - Prescribing practices for fluoxetine: a brief survey. PMID- 2307741 TI - Fluoxetine in chronic schizophrenia. PMID- 2307742 TI - Buspirone for attention deficit hyperactivity disorder? PMID- 2307743 TI - Marijuana (cannabis) use is anecdotally said to precipitate anxiety symptoms in patients with panic disorder. Is there any research evidence to support this? Also, can marijuana use precipitate or expose paranoia in patients with an underlying bipolar disorder? PMID- 2307744 TI - Studies of human gastric mucosa after application of 0.42% fluoride gel. AB - Dental prophylaxis with APF gels (1.23%) may cause gastric distress as a side effect. This gastric irritation is probably due to a direct toxic effect of fluoride (F), swallowed in conjunction with the treatment, on the gastric mucosa. The aim of the present study was to investigate whether--and to what extent--a dental treatment with 3 g of a 0.42%-F gel could affect the gastric mucosa due to inadvertent swallowing of the gel. Ten subjects underwent a control gastroscopy, and two weeks later, a second gastroscopy was performed two h after a F gel treatment. During the gastroscopy, the mucosa was examined and the injuries graded according to an arbitrary scale. Four biopsies of the antral and corpus regions of the stomach were taken and evaluated histologically. The mean (+/- SD) amount of F retained after the application was 5.1 +/- 2.1 mg, i.e., 40% of the applied amount of F. Petechiae and erosions were found in the mucosa in seven of the ten patients. The histopathological evaluation revealed changes in nine of ten patients, with the surface epithelium as the most affected component of the mucosa. The present study clearly shows that a treatment with a F gel of rather low F concentration may result in injuries to the gastric mucosa. The importance of current recommended guidelines so that the amount of F swallowed during a gel application can be minimized is emphasized. From a toxicological standpoint, the use of a low-F gel instead of a 1.23%-F gel in small children is recommended for avoidance of adverse gastric effects. PMID- 2307745 TI - Prevention of population shifts in oral microbial communities in vitro by low fluoride concentrations. AB - A continuous culture system has been used to study the effects of low (sub-MIC) levels of sodium fluoride on the stability and metabolism of a defined oral microbial community. The microflora was also subjected to glucose pulses at pH 7.0, with and without subsequent pH control. At pH 7.0, a continuous supply of 1 mmol/L NaF reduced slightly the viable counts of the oral microflora, although their proportions were relatively unaffected. At pH 7.0, during glucose pulsing, 1 mmol/L NaF prevented the rise in proportions of A. viscosus and reduced the levels of B. intermedius. Glucose pulsing without pH control and in the absence of fluoride markedly inhibited the growth of many species, and L. casei, V. dispar, and S. mutans predominated in the culture. Fluoride (1 mmol/L), either pulsed with the glucose or provided continuously, reduced both the rate of change and the degree of fall in pH, and in doing so prevented the enrichment of S. mutans in the culture. Fluoride also reduced the pH-mediated inhibition of other members of the oral community, although S. sanguis was inhibited even further. Thus, even sub-MIC levels of fluoride may have a beneficial anti-bacterial effect on dental plaque by interfering with acid production. This would reduce the pH mediated disruption to the balance of the microflora and suppress the selection of S. mutans. PMID- 2307746 TI - Sorbitol adaptation of dental plaque in people with low and normal salivary secretion rates. AB - Caries-related bacteriological and biochemical factors were studied in 12 persons with low and 11 persons with normal salivary-secretion rates before and after a four-week period of frequent mouthrinses with 10% sorbitol solution (adaptation period). After the adaptation period, an increase in total numbers of sorbitol fermenting bacteria and mutans streptococci was found in plaque samples from both groups. The pH drop in dental plaque in situ after a mouthrinse with sorbitol was more pronounced after the adaptation period, especially in the group with the low salivary-secretion rate. Increased acid production in plaque from sorbitol was also observed in the two groups in vitro. The composition of the fermentation end products was affected by the sorbitol exposure. It is suggested that in subjects with diminished natural protection against caries development, such as patients with low salivary-secretion rate, a cariogenic potential of sorbitol should be considered when this polyol is included in products that might be used frequently. PMID- 2307747 TI - Measurement of dietary and dentifrice effects upon calculus accumulation rates in the domestic ferret. AB - Most animal models for the study of calculus accumulation and control currently use rodents or dogs. In an effort to overcome limitations inherent in the use of these species, we investigated calculus formation in domestic ferrets, a species used by King et al. in the 1940's and 1950's. Ferrets are much smaller than dogs, and, unlike rodents, can be scored while alive. In this study, we examined the kinetics of calculus formation in female ferrets fed with moist canned cat food- either plain or supplemented with sucrose--and two combinations of mineral salts. An additional group given supplemented cat food was treated twice daily with regular Crest toothpaste. Animals were sedated with a 1:1 mixture of ketamine and xylazine solutions and given a mechanical prophylaxis prior to the trial period, then scored for area and extent of calculus accumulation at two, four, six, and eight weeks thereafter. The data showed that the mineral-supplemented groups accumulated calculus at a significantly faster rate than the unsupplemented or dentifrice-treated groups, but the differences were no longer significant at eight weeks. This demonstrated that the ferret is a suitable model for the study of calculus, that dietary mineral content influenced calculogenesis, and that the application of regular dentifrice initially slowed, but did not prevent, calculus accumulation. PMID- 2307748 TI - Transient and residual stress in a porcelain-metal strip. AB - Porcelain-fused-to-metal (PFM) restorations may develop cracks during processing or in-mouth service if the relative physico-mechanical properties of the porcelain and metal are highly mismatched. Precise conditions when this might occur are not known. Many processing and property variations can affect the stresses developed throughout a porcelain-metal system. To understand this, we conducted a computer simulation of stress developed in a PFM beam. The simulation considers cooling from temperatures higher than the porcelain sagpoint. The following temperature-dependent factors were incorporated: the elastic modulus, shear viscosity (porcelain), and coefficients of thermal expansion. The cooling rate dependencies of the glass transition temperature, (Tg), and the temperature distribution during cooling were also included. The results suggest that transient tensile stress at the porcelain alloy interface may result in cracks in the porcelain during cooling. Occlusal forces may set up stresses to cause cracking at the surface of the porcelain if the compressive residual stress is not high enough. PFM restorations with an alloy of high thermal expansion coefficient require rapid cooling; on the contrary, PFM restorations with the alloys of lower coefficients require slow cooling. A high cooling rate can make up for thermal expansion mismatches between the alloy and the porcelain up to 2 x 10(-6)/degrees C. Finally, the results indicated that curvature was not a sensitive indication of stress for a multimaterial beam when visco-elastic relaxation and high cooling rates are involved. For the case modeled here, curvature varied inversely with a 1/2 to 1/7th power of the stress. PMID- 2307749 TI - Hysteresis in jaw positioning following lateral stretches. AB - The purpose of this study was to examine hysteresis of the masticatory system following brief, voluntary lateral positioning of the mandible. Hysteresis was studied in ten healthy subjects, as a function of both time and distance that the mandible was held laterally off the midline. So that the effects of distance of lateral stretch on hysteresis could be studied, subjects positioned their jaws to the left or right of the midline distances of 2, 4, 6, 8, and 10 mm for ten s. So that the effects of time could be studied, the distance of lateral stretch was held a constant 8 mm for durations of two, four, six, 12, 16, and 20 s. Following each voluntary lateral stretch, subjects relaxed the muscles using EMG biofeedback and allowed the mandible to reposition itself passively. Hysteresis was defined as the difference in the mandibular resting position between pre- and post-stretch recordings. Mean hysteresis effects ranged from 0.7 mm to 1.8 mm. Hysteresis effects were found to increase with both distance and time; after eight s, however, no additional effect of time was noted. PMID- 2307750 TI - Characteristics of mandibular masticatory movement in young and elderly dentate subjects. AB - Dimensions and velocity of mandibular movement are important variables in the evaluation of masticatory and speech patterns. However, little information is available concerning elderly dentates and their oral motor function and behavior. Double recordings of a chewing period, from start to swallowing, were performed in 14 elderly (mean age, 80 years) and 30 young (mean age, 26 years) dentate subjects chewing crispbread. Three-dimensional records of mandibular movements were obtained by means of the Selspot movement analysis system, which monitors infrared light pulses from light-emitting diodes attached to the test subject. There was no difference in the duration of the total chewing cycle between the two groups. Mandibular velocity was significantly lower in the elderly group, in both the opening and the closing phases. Despite great inter-individual variations, significantly smaller mean vertical displacements of the mandible were found in the elderly than in the younger group. The lateral component in the vertical opening movement was similar for both the elderly and younger subjects. The similar chewing rates in the two groups might imply that the function of the central pattern generator was unaffected by old age. Aging was, however, associated with reduction of vertical mandibular displacement and velocity. PMID- 2307751 TI - Colonization resistance of defined bacterial plaques to Streptococcus mutans implantation on teeth in a model mouth. AB - We investigated the ability of Streptococcus mutans C67-1 to colonize simple bacterial plaques and the effects of age and stability of the pre-formed plaque on colonization resistance. Mixed-plaques of Actinomyces viscosus WVU627, 'Streptococcus mitior' LPA-1, and Veillonella dispar OMZ193 were grown on tooth segments, mounted back to back for simulation of approximal sites in a model mouth for 66 h. S. mutans C67-1 was either included in the original inoculum or super-inoculated onto the developing plaque. Inclusion of S. mutans C67-1 did not alter the total viable counts, but the proportional composition changed due to inter-species interactions. Colonization resistance of the mixed-plaque samples developed within 24 h, although S. mutans C67-1 was always able to colonize these stagnation sites. Colonization resistance of 24-hour plaque against a fresh isolate, S. mutans CP3, was also studied. There was greater colonization resistance by the basic plaque to this organism, compared with S. mutans C67-1, although the reasons for this were not clear. These initial experiments demonstrate the way in which the factors involved in bacterial colonization resistance in microbial films on teeth can be studied under controlled conditions. PMID- 2307752 TI - Taurodontism in 45,X females. AB - Orthopantomograms of 87 45,X females, 61 first-degree female relatives of these females, and a population sample of 113 normal females and 44 normal males were examined for the occurrence of taurodontism in mandibular molars. In the sample of 45,X females, two showed taurodont lower molars. In one of them, a hypotaurodont second molar was detected, while hypotaurodont third molars were found in the other. Three of the females' relatives and four of the population control females showed taurodontism, three unilaterally and four bilaterally. In all cases, the affected teeth were hypotaurodont. The results suggest that taurodontism occurs in 45,X females with a frequency similar to that in normal females. This result is not in accordance with the hypothesis that low mitotic activity of the chromosomally abnormal cells is an etiological factor in the development of taurodontism. The present findings, together with earlier results, suggest that the gene content of the X chromosome, rather than the amount of heterochromatin, is the cause of taurodontism in individuals with chromosome aneuploidy. PMID- 2307753 TI - Observations on the elastic behavior of a synthetic orthodontic elastomer. AB - The study focused on changes in elasticity that accompany water storage of a synthetic orthodontic elastomer. We plotted loading and unloading curves to permit the direct measurement of instantaneous elastic recovery (IER) and permanent set (PS) and the calculation of delayed recovery (DR). We obtained baseline data by testing dry as received material. Comparable tests were performed on material that had been stored in water at 37 degrees C for one, seven, 14, 42, and 70 days. Gas chromatography-mass spectrometry was used for analysis of organic substances leached from the elastomer by water. A two-way ANOVA revealed that extension distance and water storage duration affected load requirement, IER, PS, and DR. The presence of leachable organic substances in 14 , 42-, and 70-day storage water was evidence of time-dependent matrix decomposition. Findings from tests of elastic performance and analysis of specimen storage water indicate that exposure of the elastomer to water leads first to weakening of noncovalent forces and subsequently to degradation. PMID- 2307754 TI - Petri dish to operatory: bridging the gap. PMID- 2307755 TI - Dental hygiene curriculum model for transition to future roles. PMID- 2307756 TI - Dental implantology in U.S. dental schools. PMID- 2307757 TI - An analysis of community service activities in U.S. dental schools. PMID- 2307758 TI - Bulimia and anorexia nervosa in dental and dental hygiene curricula. PMID- 2307759 TI - Assignment of dental school patients using periodontal treatment need indices. PMID- 2307760 TI - Smoking policies of U.S. dental schools. PMID- 2307761 TI - Literalism as a marker of hypnotic "trance": disconfirming evidence. AB - The responses given by highly hypnotizable, hypnotic subjects and those of unhypnotizable subjects who simulated hypnosis to questions of the type, "Do you mind telling me your name?" and "Do you mind standing up?" were contrasted. The purpose was to examine Erickson's (1980) assertion that literalism (answering "yes" or "no" verbally or nonverbally without any cognitive elaboration) is a marker of hypnotic "trance." Simulators exhibited a greater rate of literalism than hypnotic "virtuosos" (i.e., extreme scorers on both group and individual hypnotizability measures). Hypnotized subjects and nonhypnotized subjects approached in the campus library responded comparably. Because less than a third of hypnotic virtuosos responded literally, our results strongly refuted Erickson's assertion that literalism is a cognitive feature of hypnosis. PMID- 2307762 TI - Regional brain electrical asymmetries discriminate between previously depressed and healthy control subjects. AB - Baseline resting electroencephalogram (EEG) activity was recorded from 6 normothymic depressives and 8 controls using three different reference montages. Power in all frequency bands was extracted by Fourier transformation. Significant Group X Region X Hemisphere interactions were found consistently for alpha band power only. Previously depressed subjects had less left-sided anterior and less right-sided posterior activation (i.e., more alpha activity) than did never depressed subjects. Previously depressed subjects had no history of pharmacological treatment and did not differ from controls in emotional state at the time of testing. The pattern of anterior and posterior asymmetry in the previously depressed subjects is similar to that found in acutely depressed subjects and suggests that this may be a state-independent marker for depression. PMID- 2307763 TI - Controlled prospective study of postpartum mood disorders: comparison of childbearing and nonchildbearing women. AB - A controlled prospective study was undertaken to determine the extent to which pregnancy and the puerperium are associated with increased risk for minor and major depression, depressive symptom-atology, and poor social adjustment. A large sample of childbearing (CB) women were recruited during the second trimester of pregnancy along with an equal sized, matched sample of nonchild-bearing (NCB) women. Ss were assessed multiple times during pregnancy and after delivery by questionnaire and through personal interview on measures of depression and other mood states and marital and social adjustment. There were no differences between CB and NCB Ss with respect to rates of minor and major depression during pregnancy or after delivery. However, CB women experienced significantly higher levels of depressive symptomatology and poor social adjustment than NCB women during late pregnancy and the early puerperium. PMID- 2307764 TI - Bulimia and taste: possible interactions. AB - Potential abnormalities of taste were examined in bulimic subjects who purged by vomiting and in controls. When spatial testing of the tongue and palate was performed by direct local application of sweet, salty, sour, and bitter solutions, bulimics showed a selective spatial loss on the palate. The palate may be affected by purging because vomit is directed toward the roof of the mouth where the palate receptors are located. The data suggest that the acid in vomit damages these receptors. Bulimics and controls did not differ in their basal ratings of intensity or pleasantness of sweet, salty, sour, and bitter stimuli when these were sipped rather than directly applied to the tongue. However, after ingesting a glucose load, controls found sweet taste significantly less pleasant, whereas bulimics did not. The results suggest that bulimics may also have an abnormal experience of satiety. PMID- 2307765 TI - Categorical versus dimensional status of borderline personality disorder. AB - One of the many controversies concerning the borderline personality disorder (BPD) diagnosis is whether the construct refers to a categorical or dimensional variable. The current study used Meehl's (1973) maximum covariance analysis to investigate this issue. The charts of 409 psychiatric inpatients were systematically reviewed for the presence of BPD and dysthymic symptoms. Charts of 244 inpatients were also reviewed to assess the presence of indicators of male sex, a categorical variable. The results for BPD and dysthymia were consistent with a dimensional model, whereas those for male sex were consistent with a categorical model. A dimensional model of classification of BPD is recommended, and suggestions for future research are provided. PMID- 2307766 TI - Psychophysiologic responses to combat imagery of Vietnam veterans with posttraumatic stress disorder versus other anxiety disorders. AB - We used psychophysiologic techniques to assess responses to imagery of psychologically stressful past experiences in medication-free Vietnam combat veterans classified, on the basis of DSM-III-R criteria into posttraumatic stress disorder (PTSD; n = 7) or non-PTSD anxiety disorder (anxious; n = 7) groups. Scripts describing each individual's combat experiences were recorded and played back in the laboratory. Ss were instructed to imagine the events the scripts portrayed while heart rate, skin conductance, and frontalis electromyogram were recorded. PTSD Ss' physiologic responses were higher than those of anxious Ss. A discriminant function derived from a previous study of PTSD and mentally healthy combat veterans identified 5 of the 7 current PTSD Ss as physiologic responders and all 7 of the anxious Ss as nonresponders. Results of this study replicate and extend results of the previous study and support the validity of PTSD as a separate diagnostic entity. PMID- 2307767 TI - Sex differences and adolescent depression. AB - This study investigates the role of certain psychosocial variables--sex, age, body image/self-esteem, self-consciousness, stressful life events, and the degree to which an individual identifies with the cultural stereotype of masculinity--as correlates and antecedents to depression in adolescents and explores possible intraindividual mediators of the stress-depression relationship in adolescents. A battery of self-report measures was administered to public high school students in Grades 9-12 in their classrooms at two different times 1 month apart. Female adolescents reported more depressive symptoms, self-consciousness, stressful recent events, feminine attributes, and negative body image and self-esteem; no age effects were obtained. Results suggest a model of adolescent depression in which body/self-esteem and stressful recent events are significant contributors. PMID- 2307768 TI - The prevalence of nightmares and their independence from anxiety. AB - Although several studies have examined the prevalence of nightmares and their relationship to anxiety, this is the first to have used daily dream logs, rather than retrospective self-reports, to monitor nightmare frequency. 220 undergraduates were administered self-report measures of anxiety and for 2 weeks recorded the number of their nightmares in logs. 47% of Ss reported at least one nightmare during the study period. The dream logs yielded an estimated mean annual nightmare frequency of 23.6, which is 2.5 times as great as the estimate yielded by retrospective reports (p less than .01). Nightmare frequency and anxiety were uncorrelated. The findings indicate that nightmares are more prevalent than has been reported, and their frequency unrelated to self-reported anxiety. PMID- 2307769 TI - Nonpsychotic postpartum depression among adolescent mothers. AB - This study examined the extent to which childbearing increases vulnerability to clinical depression and depressive symptomatology among primiparous adolescent girls (ages 14 to 18). Childbearing Ss (n = 128) were assessed during pregnancy, 6 weeks postpartum, and 1 year postpartum. Matched nonchildbearing Ss (n = 114) were assessed at corresponding time points. Six weeks postpartum, 6% of the childbearing adolescents met Research Diagnostic Criteria for major depression and 20% for minor depression. These rates were not significantly different from those found for nonchildbearing Ss (4% major depression, 10% minor depression). However, higher rates of somatic symptoms of depression were found among the childbearing Ss than among the nonchildbearing Ss. PMID- 2307770 TI - Effects of alcohol on psychophysiological hyperreactivity to nonaversive and aversive stimuli in men at high risk for alcoholism. AB - Psychophysiological reactivity to nonaversive (1-KHz, 70-db tones) and aversive stimuli (shock) was examined in nonalcoholic men with multigenerational family histories (MFH) of alcoholism and family history negative (FH-) men, while sober and after consuming alcohol. In comparison with FH- Ss, sober MFH Ss had significantly larger skin conductance (SC) orienting responses (ORs), shorter OR latencies, slower habituation rates to the tones, and larger increases in heart rate and vasoconstriction to the shock. Alcohol dampened the magnitude of the SC OR to the tones and the degree of cardiovascular reactivity to the shocks and increased the habituation rate to the tones in MFH Ss only. Alcohol consumption also increased the SC-OR recovery time in FH- Ss only. The MFH Ss' pattern of psychophysiological hyperreactivity is discussed in terms of a potential dysfunction in stimulus-response regulation. PMID- 2307771 TI - A longitudinal study of antisocial behaviors in early adolescence as predictors of late adolescent substance use: gender and ethnic group differences. AB - Data from the National Longitudinal Youth Survey (NLSY) were analyzed to study interrelationships between antisocial behaviors in early adolescence (ages 14-15) and late adolescent alcohol and drug use 4 years later (when adolescents were 18 19). Correlations between classes of antisocial behaviors in early adolescence and substance use in late adolescence were of higher magnitude and more uniform for men than for women; for women, property offenses (e.g., vandalism) in early adolescence were more highly associated with alcohol use, alcohol-related problems, and illicit drug use in late adolescence than with either status offenses or transgressions against persons. Multiple regression analyses indicated that early-adolescent substance involvement was a significant predictor of late-adolescent alcohol and drug use. Additional significant predictors included early adolescent general delinquency, male gender, and non-Black ethnicity. PMID- 2307772 TI - Ecology of depression in late childhood and early adolescence: a profile of daily states and activities. AB - This study investigated daily states and time use patterns associated with depression. Four hundred eighty-three 5th to 9th graders reported on their experience when signalled by pagers at random times. Depressed youth reported more negative affect and social emotions, lower psychological investment, lower energy, and greater variability in affect. These differences were weaker for 5th and 6th graders, suggesting that self-reported feeling states are a poor indicator of depression prior to adolescence. No differences were found in the daily activities of depressed youths nor in the amount of time spent alone, but depressed youths experienced other people as less friendly and more often reported wanting to be alone, especially when with their families. They also spent less time in public places and more time in their bedrooms. Finally, depressed boys, but not girls, spent much less time with friends, particularly of the same sex, suggesting that social isolation is more strongly associated with depression for boys. PMID- 2307773 TI - Acoustic radiation pressure on a rigid cylinder: an analytical theory and experiments. AB - Simple and general analytical expressions are derived for the acoustic radiation force on a long rigid cylinder with a small diameter, whose axis is perpendicular to the wave propagation. Results are expressed in terms of the time-averaged densities of kinetic and potential energies of the incident sound field. For the case of a standing-wave field, which was used in these experiments, the theoretical results agree well with the experimental observations. PMID- 2307774 TI - Direction-dependent spectral properties of cat external ear: new data and cross species comparisons. AB - Free-field to eardrum transfer functions were measured in anesthetized cats inside an anechoic chamber. Direction-dependent transformations were determined by measurement of sound-pressure levels using a small probe tube microphone surgically implanted in a ventral position near the tympanic membrane. Loudspeaker and probe microphone characteristics were eliminated by subtraction of the signal recorded in the free field with no animal present. Complexities of the transfer function, which include the presence of prominent spectral notches in the 8- to 18-kHz frequency region, are due primarily to the acoustical properties of the pinna. Differential amplification of frequency components within the broadband stimulus occurs as a function of source direction. Spectral features vary systematically with changes in both elevation (EL) and azimuth (AZ). The contrast between a notch and its shoulders is enhanced in the interaural spectral records. Spectral data from single source locations and spatial data for single frequencies at many locations are presented and comparisons with other species are drawn. It is suggested that spectral features in the 8- to 18-kHz region provide some of the necessary spectral information for sound localization and that the contrast in spectral energy between the frequencies at the notch and its shoulders is a potential directional cue. PMID- 2307775 TI - Inner hair cell responses to the 2f1-f2 intermodulation distortion product. AB - Recordings of dc and ac receptor potentials from pigmented guinea pig inner hair cells indicate strong responses to the 2f1-f2 intermodulation tone when f1 and f2 are greater than the hair cell characteristic frequency and do not cause a response when given individually. The effective magnitude of this cubic distortion product (CDP) was about 25-30 dB below equal sound level primaries over a 20-30-dB range of their sound levels. The relative strength of the CDP declined at a rate greater than 180-dB/oct separation of the primaries. When magnitude of f1 or f2 was held constant, the growth of CDP was nonmonotonic, exhibiting a distinct maximum. With a constant level of f1 or f2, optimal CDP was produced when the level of f2 was 10-15 dB greater than f1. Strong two-tone suppression from the primaries has a role in shaping the CDP growth. The ac receptor potentials of the CDP show a 150 degrees-200 degrees phase shift when the primaries are increased over a 50-dB range. These results support the hypothesis of a propagated CDP in the cochlea and are consistent with the major features of related studies of human psychoacoustic experiments, afferent nerve neural rate functions, and ear canal distortion products. PMID- 2307776 TI - Physiological mechanisms of psychophysical masking: observations from auditory nerve fibers. AB - Masking might be due either to the spread of the excitation produced by the masker to the place of the tone signal along the cochlea or to the suppression of the response to the signal by the masker. In order to identify the contributions of these two mechanisms to tone-on-tone masking, masked thresholds of auditory nerve fibers were measured in anesthetized cats using the same stimulus paradigms and detection criteria as in psychophysics. Suppressive masking was identified by comparing thresholds for simultaneous masking with those for a nonsimultaneous masking technique resembling pulsation thresholds. These nonsimultaneous thresholds do not include the contribution of suppression to masking because suppression only occurs for stimuli that overlap in time. For each masker and signal frequency, the fibers with the lowest (or "best") masked thresholds had characteristic frequencies (CF) slightly on the opposite side of the masker frequency with respect to the signal frequency, consistent with the psychophysical phenomenon of off-frequency listening. Patterns of best masked thresholds against signal frequency resembled psychophysical masking patterns in that they showed a maximum for signal frequencies close to the masker, and a skew toward high frequencies. Masking was found to be both excitatory and suppressive, with the relative contribution of the two mechanisms depending on the frequency separation between signal and masker. Suppressive masking was large for signal frequencies well above the masker. For these conditions, simultaneous thresholds grew more rapidly with masker level than did nonsimultaneous thresholds, suggesting that the upward spread of masking is largely due to the growth of suppression rather than to that of excitation. PMID- 2307777 TI - Detectability of interaural delays over select spectral regions: effects of flanking noise. AB - Zurek [P. M. Zurek, J. Acoust. Soc. Am. Suppl. 1 78, S18 (1985)] noted what he termed "spectral dominance" in sensitivity to interaural delay for broadband stimuli. He found that interaural delays presented solely within high-frequency spectral regions were difficult, if not impossible, to detect in the presence of spectrally flanking, gated, diotic noise. In order to see if spectral dominance is a general result of the processing of interaural delays in broadband stimuli, similar experiments were conducted utilizing both gated and continuous flanking noises that were interaurally identical (diotic) or completely uncorrelated. Beyond replicating Zurek's basic findings, the data strongly suggest that the processing of interaural delays was largely unaffected when the flanking sounds were continuous and diotic. When the flanking sounds were interaurally uncorrelated, sensitivity was affected, but not drastically, for both gated and continuous conditions. Consequently, it appears that any inability to cope with conflicting interaural cues across spectral regions may be observed only under restricted conditions. PMID- 2307778 TI - Sharpness and amplitude envelopes of broadband noise. AB - This paper discusses how amplitude envelope shapes, sound-pressure level, and duration of broadband noise affect sharpness and brightness. In the first experiment, sharpness, brightness, and similarity were judged for paired stimuli by 13 subjects. The stimuli consisted of broadband noise with different types of amplitude envelopes, sound-pressure levels, and duration. Experimental results were analyzed with a multidimensional scaling technique. In addition, the second experiment measuring the point of subjective equality (PSE) of sharpness was carried out for four subjects. The results of these two experiments showed large individual differences in sharpness judgment, difficulty in brightness judgment for the stimuli used in the experiments, and influence of the amplitude envelope shapes on sharpness. The individual differences observed in sharpness judgment were explained by the differences between weights given to two psychological dimensions: loudness and subjective duration. This study forms a basis for understanding sharpness of nonsteady sounds. PMID- 2307779 TI - Evaluation of a spectrum target prediction model in speech perception. AB - A model of a spectrum target prediction mechanism is proposed and evaluated by comparing predicted values with results of psychoacoustic experiments. When the trajectory of the cepstrally smoothed LPC spectrum is approximated by a second order critically damped system, the proposed model can estimate target values using short-period spectrum sequences (50 ms) without being given the onset positions of the spectral transition. Additionally, this model decreases the length of transitional sounds and recovers vowel characteristics neutralized by coarticulation. Moreover, this model compensates for the transitions of syllables and extracts stable characteristics from syllable transitions. This model is applicable to coarticulation recovery in speech signal processing. PMID- 2307780 TI - Vowel-onset detection. AB - An algorithm is presented that correctly detects the large majority of vowel onsets in fluent speech. The algorithm is based on the simple assumption that vowel onsets are characterized by the appearance of rapidly increasing resonance peaks in the amplitude spectrum. Application to carefully articulated, isolated words results in a high number of false alarms, predominantly before consonants that can function as vowels in a different context such as another language or as a syllabic consonant. After applying some modifications in the setting of some parameters, this number of false alarms for isolated words can be reduced significantly, without the risk of a large number of missed detections. The temporal accuracy of the algorithm is better than 20 ms. This accuracy is determined with respect to the perceptual moment of occurrence of a vowel onset as determined by a phonetician. PMID- 2307781 TI - Ultrasonic spectroscopy in bovine serum albumin solutions. AB - Ultrasonic absorption and velocity spectra in bovine serum albumin (BSA) aqueous solutions have been measured at 20 degrees C over the broad frequency range 0.1 1600 MHz in the pH range 1.5-13.2. Five different techniques were used: the plano concave resonator, plano-plano resonator, pulse-echo overlap, Bragg reflection, and high-resolution Bragg reflection methods. The absorption spectrum at neutral pH was well fitted to the relaxation curve assuming a distribution of relaxation frequency with a high-frequency cutoff and long low-frequency tail. The relaxation behavior was interpreted in terms of various degrees of hydration of BSA molecules. At acid pH's, excess absorption over that at pH 7 was explained by double relaxation. The pH dependences of the relaxation frequency and maximum absorption per wavelength showed that the relaxation at about 200 kHz was related to the expansion of molecules and that at 2 MHz resulted from the proton transfer reaction of carboxyl group. At alkaline pH's, the excess absorption was explained by triple relaxation. The relaxation at about 200 kHz was associated with a helix coil transition, and the two relaxations at 2 and 15 MHz were attributed to the proton transfer reactions of phenolic and amino groups, respectively. The rate constants and volume changes associated with these processes were estimated. PMID- 2307782 TI - A comparison among three measures of cross-spectral processing of amplitude modulation with tonal signals. AB - Results were obtained from three paradigms used to study cross-spectral processing of envelope modulation [comodulation masking release (CMR), comodulation detection difference (CDD), and modulation detection interference (MDI)]. When tonal carriers separated by two octaves (flanking tone at 1000 Hz and target tone at 4000 Hz) were amplitude modulated at 20 Hz, there was no evidence of a cMR or CDD effect, but there was substantial MDI. PMID- 2307783 TI - Voyager flight crew hearing threshold levels resulting from 5- and 9-day continuous in-flight noise exposure. AB - The flight crew of the Voyager aircraft were continuously exposed to a broadband noise for nearly 5 days during a trial flight, and for over 9 days during their nonstop flight around the world. Evaluation of the threshold shifts resulting from these exposures represents a unique opportunity to study the effect of human exposure to intense continuous noise for long durations. Postflight audiometry demonstrated that the 9-day flight did not result in larger hearing threshold shifts than those following the 5-day flight. Neither crewmember incurred a permanent threshold shift from these exposures. PMID- 2307784 TI - A computer interface for psychophysical and speech research with the Nucleus cochlear implant. AB - A computer interface has been designed and implemented that allows presentation of biphasic pulse stimuli to patients with the Nucleus Ltd./Cochlear Corporation cochlear implant. The one version of the interface connects to a standard parallel output port of a PC or AT compatible computer, and another version plugs directly into a standard PC/XT bus slot. The host computer sends a stream of bytes to the parallel port that specifies the configuration of the desired output pulses. Upon receipt of the data, the interface generates the appropriate burst sequence that is delivered to the patient's external transmitter coil. The coded information is interpreted by the internal receiver that delivers the pulse to the specified electrodes at the specified amplitude and pulse width. This interface makes it possible to interleave pulses on two or more electrode pairs, to modulate the amplitude or timing of a pulse sequence, or to sweep a stimulus across the electrode array. Investigators can achieve stimulus control with this interface that allows them to conduct psychophysical, electrophysiological, and speech experiments not possible through the patient's speech processor or with available clinical interfaces. PMID- 2307785 TI - The spectrum of diseases of small coronary arteries and their physiologic consequences. AB - There is a wide spectrum of abnormalities in the structure of small coronary arteries, with regard both to the portion of the arterial wall involved and to the histologic nature of the disease. A fuller understanding of this spectrum permits more useful interpretation of the pathophysiologic basis for the functional consequences of small coronary artery disease. In this review based on personal observations during examination of more than 1,000 human hearts postmortem there is initially a description of the wide variety of structural abnormalities, then a discussion of the functional consequences of these abnormalities and finally a section of general comments to weave together the structural and functional discussion in the context of clinical evaluation of patients who have small coronary artery disease. Future studies should apply fractal analysis and quantitative topology, methods that lend themselves particularly well to an investigation of the progressively smaller branching of the human coronary tree. PMID- 2307786 TI - The significance of coronary reserve in clinical heart disease. AB - The clinical syndrome "coronary insufficiency with normal coronary arteriogram" is found in approximately 10% to 20% of patients with exercise-induced coronary insufficiency. In most of these cases, disturbances of the coronary microcirculation are present. They can appear in vascular diseases (arterial hypertension, systemic immunopathies, immune complex vasculitis), in rheologic diseases (paraproteinemia, hyperlipoproteinemia, polyglobulia) and in disturbances of transport and diffusion of oxygen (carbon monoxide intoxication, methemoglobinemia). The clinical diagnosis is based on the usual diagnostic procedures (electrocardiogram, exercise electrocardiogram, responsiveness to nitroglycerin), as well as on newer functionally oriented diagnostic procedures (determinations of coronary blood flow and coronary vascular reserve, production of lactate, serologic findings, histology and immune histology of peripheral arteries, measurements of viscosities in both plasma and blood). Many clinically relevant disturbances in the coronary microcirculation can thus be detected and treated on a rational basis by management of the underlying main disease, that is, by treatment of the vascular, rheologic and metabolic disorders. Persistent angina pectoris in the presence of a normal coronary arteriogram does not represent an end to coronary diagnostic procedures, but introduces the clinical task of using all diagnostic possibilities to enable functional and therapeutic assessment of the coronary microcirculation. PMID- 2307787 TI - Arteriographic evaluation of small coronary arteries. AB - The purpose of this study was to determine the accuracy of imaging small coronary arteries with current radiographic equipment. Phantom assessments were performed using a phantom that comprises a large array of circular objects of varying diameter and contrast density. More objects could be identified in the moving cinearteriogram than in single cine frames. Using the largest object as the calibration standard, diameters less than 1 mm were markedly overestimated. A simple morphometric method showed that arteriographic visualization of small vessels was better by digital processing than by cine recording. However, there was no statistically significant difference in the average size of the smallest identifiable vessel by either method (0.5 versus 0.51 mm). After correcting for overestimation and the inaccurate imaging of the smallest detectable vessels, the practical arteriographic threshold is approximately 0.5 mm. Parametric imaging holds promise, but its significance for evaluating small vessel disease has yet to be determined. PMID- 2307788 TI - Natural history of left ventricular thrombi: their appearance and resolution in the posthospitalization period of acute myocardial infarction. AB - A series of 198 consecutive patients with acute myocardial infarction were prospectively studied before hospital discharge and during 24.0 +/- 8.6 months of follow-up. A predischarge thrombus was found in 38 (31%) of 124 patients with anterior infarction but in none of 74 patients with inferior infarction (p less than 0.001). Early thrombolytic therapy in 34 patients did not decrease the rate of thrombus occurrence. Acute anterior infarction, ejection fraction less than or equal to 35% and apical dyskinesia or aneurysm (but not akinesia) were significantly related to the appearance of thrombus during hospitalization by stepwise logistic regression analysis. Echocardiographic follow-up of 159 patients for at least 6 months (mean 26.6 +/- 8.4) revealed that thrombus disappeared in 14 (48%) of 29. Disappearance of thrombus was related to predischarge apical akinesia (but not dyskinesia) and to warfarin therapy during the follow-up period. A new thrombus first appeared after hospital discharge in 13 of 130 patients, and in 7 of the 13 it resolved during further follow-up. Thus, 30% (13 of 42) of thrombi in these patients appeared after discharge from the hospital. Three factors were related to occurrence of new thrombi during the follow-up period: deterioration in left ventricular ejection fraction, predischarge ejection fraction less than or equal to 35% and ventricular aneurysm or dyskinesia. Systemic embolism occurred in six patients, all with a predischarge thrombus (p less than 0.001). Mobility of the thrombus was the only variable significantly related to subsequent embolic events (p = 0.001) by logistic regression analysis. Thus, the predischarge echocardiogram identifies patients with thrombus and those at highest risk of embolic events. It can indicate patients who are likely to have thrombus resolution and those at risk of developing a new thrombus after hospital discharge. Follow-up echocardiograms may help in guiding the length of long-term anticoagulant therapy. Four additional patients with a predischarge apical mobile thrombus (not part of the consecutive series) received thrombolytic therapy. In two of the four, lysis of thrombus was achieved without complications, but systemic embolism occurred in the other two, and proved fatal in one. PMID- 2307789 TI - Inversion of the normal interatrial septum convexity in acute myocardial infarction: incidence, clinical relevance and prognostic significance. AB - Inversion of the normal interatrial septum convexity has been described in patients with right atrial pressure or volume overload, but there is no reference to this abnormality in acute myocardial infarction. A group of 576 consecutive patients with acute infarction and serial echocardiographic studies were prospectively evaluated during a mean follow-up period of 406 days. Inverted interatrial septum convexity was found in 30 patients (5.2%); 29 of the 30 presented with inferior infarction with right ventricular involvement (29 [24.4%] of 119) and the remaining presented with cardiac tamponade secondary to heart rupture. The incidence of inverted interatrial septum convexity rapidly decreased, and after 3 months it was present in only five patients. All patients with inverted interatrial septum convexity had a right atrial pressure greater than or equal to pulmonary capillary pressure, a relation found in only 2 of 43 patients with right ventricular involvement and normal septal convexity. In patients with right ventricular infarction, right atrial pressure was higher in the presence of inverted septal convexity (15.9 +/- 4.1 versus 10.5 +/- 4.1 mm Hg, p less than 0.0001) and the incidence of hypotension (10 [34.4%] of 29 versus 15 [17.4%] of 90, p = 0.04) and third degree atrioventricular block (10 [34.4%] of 29 versus 11 [12.2%] of 90, p = 0.006) as well as the mortality rate after 3 months (9 [31%] of 29 versus 11 [12.2%] of 90, p = 0.04) were higher in the presence of inverted convexity than in patients with normal septal convexity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307790 TI - The interatrial septum in acute myocardial infarction. PMID- 2307791 TI - Relation between extent of left ventricular hypertrophy and diastolic filling abnormalities in hypertrophic cardiomyopathy. AB - In hypertrophic cardiomyopathy, the relation between left ventricular diastolic impairment and magnitude of left ventricular hypertrophy has not been clearly defined. In the present study, Doppler echocardiographic indexes of left ventricular diastolic filling were compared in 78 patients with hypertrophic cardiomyopathy and in 72 normal control subjects of similar age, and the relation between abnormalities of diastolic filling and magnitude of left ventricular hypertrophy was assessed. In patients with hypertrophic cardiomyopathy, isovolumic relaxation was prolonged (94 +/- 25 ms); peak early diastolic flow velocity (53 +/- 18 cm/s), deceleration of flow velocity in early diastole (341 +/- 142 cm/s2) and the ratio between early and late peaks of flow velocity (1.6 +/- 0.9) were reduced; and peak late diastolic flow velocity was increased (38 +/ 15 cm/s) compared with values in control subjects (76 +/- 12 ms, 65 +/- 12 cm/s, 512 +/- 131 cm/s2, 2.3 +/- 0.8 and 30 +/- 7 cm/s, respectively; p less than 0.001). Individual patient analysis showed that diastolic filling was abnormal in 52 (67%) of the 78 patients with hypertrophic cardiomyopathy. However, within the patient group, none of the Doppler diastolic indexes showed a significant correlation with maximal left ventricular wall thickness or the wall thickness index (correlation coefficients ranged from -0.15 to 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307792 TI - Impaired left ventricular relaxation in hypertrophic cardiomyopathy: relation to extent of hypertrophy. PMID- 2307793 TI - Determination of aortic valve area by two-dimensional and Doppler echocardiography in patients with normal and stenotic bioprosthetic valves. AB - To assess the feasibility and accuracy of determining bioprosthetic aortic valve area from two-dimensional and Doppler echocardiographic measurements, three partially overlapping groups were selected from 55 patients with such bioprosthetic valves and adequate Doppler studies. These were Group 1, 37 patients with recent aortic valve replacement surgery and no clinical or echocardiographic evidence of valve dysfunction; Group 2, 12 patients with prosthetic valve stenosis documented by cardiac catheterization; and Group 3, 22 patients with both Doppler and catheterization studies in whom noninvasive and invasive determinations of aortic valve area could be directly compared. Left ventricular outflow tract diameter was measured from two-dimensional still frame images. Flow velocity proximal to the aortic valve, transvalvular velocity and acceleration time were determined from pulsed and continuous wave Doppler spectra. Aortic valve gradient was calculated with the modified Bernoulli equation and valve area by the continuity equation. In the 37 patients with a normally functioning valve, the calculated mean gradient ranged from 5 to 25 mm Hg (average 13.6 +/- 5.2) and valve area from 1.0 to 2.3 cm2 (mean 1.6 +/- 0.31). Linear regression analysis of prosthetic aortic valve area determined by Doppler imaging and cardiac catheterization demonstrated a high correlation (r = 0.93) between the two techniques. Comparison of the patients with and without prosthetic valve stenosis revealed statistically significant differences in mean gradient (42.8 +/- 12.3 versus 13.6 +/- 5.2 mm Hg; p = 0.0001), acceleration time (116 +/- 15 versus 80 +/- 13 ms; p = 0.0001) and valve area by the continuity equation (0.80 +/- 0.16 versus 1.6 +/- 0.31 cm2; p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307794 TI - Doppler echocardiographic evaluation of stenotic bioprosthetic aortic valves. PMID- 2307795 TI - Characterization of double potentials in human atrial flutter: studies during transient entrainment. AB - Double potentials, defined as atrial electrograms with two discrete deflections per beat separated by an isoelectric interval or a low amplitude baseline, have been observed during right atrial endocardial mapping of human atrial flutter. In this study, bipolar atrial electrograms were recorded during atrial flutter (mean cycle length 235 +/- 27 ms [+/- SEM]) from the high right atrium, the His bundle region, the coronary sinus and at least 30 right atrial endocardial mapping sites in 10 patients. Double potentials were recorded from the right atrium in all patients during atrial flutter. Double potentials were evaluated during transient entrainment of atrial flutter by rapid high right atrial pacing in 5 of the 10 patients. In four of these five patients during such transient entrainment 1) one deflection of the double potential was captured with a relatively short activation time (mean interval 89 +/- 45 ms) and the other deflection was captured with a relatively long activation time (mean interval 233 +/- 24 ms), producing a paradoxical decrease in the short interdeflection interval from a mean of 75 +/- 20 ms to a mean of 59 +/- 24 ms; and 2) the configuration of the double potential remained similar to that observed during spontaneous atrial flutter. On pacing termination 1) the two double potential deflections were found to be associated with two different atrial flutter complexes in the electrocardiogram (ECG); 2) the previous double potential deflection relation resumed; and 3) when sinus rhythm was present, the double potentials were replaced by a broad, low amplitude electrogram recording at the same site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307796 TI - Assessment of the intrapulmonary ventilation-perfusion distribution after the Fontan procedure for complex cardiac anomalies: relation to pulmonary hemodynamics. AB - In 12 patients who underwent the Fontan procedure for complex cardiac anomalies, lung scanning with xenon-133 was performed to assess the intrapulmonary ventilation-perfusion distribution, and comparison was made with a control group. All data were then analyzed in relation to either pre- or postoperative pulmonary hemodynamic data. In ventilation scans, the intrapulmonary distribution in the right lung was almost normal. In perfusion scans, an abnormal increased upper to lower lobe perfusion ratio greater than the normal value found in the control group was noted in seven patients (58.3%). There was a significant correlation (p less than 0.02) between the upper to lower lobe perfusion ratio and postoperative pulmonary vascular resistance. Furthermore, this perfusion ratio correlated inversely with the preoperative (p less than 0.005) and postoperative (p less than 0.02) right pulmonary artery area index, defined as the ratio of cross sectional area to the normal value. Of five patients with less than 90% arterial oxygen saturation, four showed an abnormal distribution of pulmonary blood flow greater than the normal perfusion ratio. No patient had evidence of a pulmonary arteriovenous fistula by the echocardiographic contrast study. These results suggest that abnormal distribution of pulmonary blood flow to the upper lung segment may develop in patients after the Fontan procedure, and that insufficient size of the pulmonary artery before operation and the consequent postoperative elevation of pulmonary vascular resistance may be responsible for this perfusion abnormality. PMID- 2307798 TI - Coronary angioplasty for total occlusion: ongoing problems despite improving results. PMID- 2307797 TI - Procedural outcome of angioplasty for total coronary artery occlusion: an analysis of 971 lesions in 905 patients. AB - This study analyzes the results of angioplasty in 905 consecutive patients with 971 total occlusions. The procedures were performed by five cardiologists from January 1980 to January 1989 at one institution. The overall success rate per lesion was 72%. Even the most experienced operator (524 occlusions attempted) has continued to improve on a learning curve, with 83% of his most recent 100 occlusions successfully dilated. Procedural death occurred in seven patients (0.8%), five patients (0.6%) sustained a myocardial infarction and seven patients (0.8%) required urgent coronary bypass surgery. Complications were significantly more likely to occur in the elderly, in women and in patients with triple vessel disease and depressed left ventricular function. Compared with angioplasty in 6,950 patients with nonoccluded stenoses, angioplasty of total occlusions had a lower success rate (72% versus 96%, p = 0.001), although the complication rate was also lower (1.9% versus 3.5%, p = 0.01). Multivariate analysis of 20 clinical and angiographic variables in 100 consecutive patients undergoing angioplasty of 104 total occlusions in 1988 identified only bridging collateral vessels (85% success rate if absent versus 18% if present, p less than 0.001) and a tapered occlusion morphology (88% success rate if present versus 59% if absent, p = 0.01) as independent correlates of procedural outcome. Other variables, including the estimated duration of occlusion, lesion length and location, and extent of disease were unrelated to technical success. With present techniques and sufficient operator experience, 70% to 80% of total occlusions can be successfully recanalized by coronary angioplasty with a complication rate of less than 2%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307799 TI - The thromboxane receptor antagonist SQ 30,741 reduces myocardial infarct size in monkeys when given during reperfusion at a threshold dose for improving reflow during thrombolysis. AB - The threshold dose of the selective thromboxane receptor antagonist SQ 30,741 for increasing reflow during thrombolysis was identified and then evaluated in a model of myocardial ischemia with reperfusion. In anesthetized cynomolgus monkeys, stenotic carotid arteries were occluded with a platelet-rich thrombus by electrical stimulation and recanalized with streptokinase (680 U/min intraarterially for 1 h) and heparin (200 U/kg + 120 U/h intravenously for 3 h). Concurrent administration of SQ 30,741 (2.1 mg/kg + 0.5 mg/kg per h intravenously for 3 h; n = 4) enhanced the extent of reflow 174% compared with saline solution (n = 4; p less than 0.05) during the third hour, when lower doses were ineffective. This threshold dose was tested in anesthetized African green monkeys subjected to 90 min of left circumflex coronary artery occlusion and 5 h of reperfusion. SQ 30,741 (n = 8) or saline solution (n = 11) was administered 2 min before reperfusion and continued throughout reperfusion. The heart was removed on termination of reperfusion and perfused in vitro with Evans blue and triphenyltetrazolium chloride dyes to stain tissue at risk and infarcted tissue, respectively. The percent of left ventricle at risk did not differ between saline (37 +/- 4%) and SQ 30,741-treated (35 +/- 3%) monkeys. In contrast, infarcted tissue expressed as percent of the left ventricle at risk was less (p less than 0.01) in monkeys receiving SQ 30,741 (31 +/- 2%) than in those receiving saline solution (49 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307800 TI - Bradycardia and syncope as manifestations of partial epilepsy. AB - Although transient increases in heart rate typically occur, bradycardia has infrequently been noted in association with partial seizures. Five patients with temporal lobe epilepsy are described in whom sinus bradyarrhythmias and syncope were prominent manifestations of seizure activity. Partial improvement occurred in one of two patients in whom a permanent pacemaker was implanted before a diagnosis of epilepsy was established. Treatment with phenytoin or carbamazepine resulted in nearly complete resolution of symptoms in all five patients. Because pacemaker implantation does not prevent recurrent symptoms, but anticonvulsant therapy does, this experience underscores the importance of considering the diagnosis of partial epilepsy in selected patients with sinus bradyarrhythmias and syncope. PMID- 2307801 TI - The American College of Cardiology and our affiliate-in-training members. PMID- 2307802 TI - Millimolar obscurity: implementing SI units. PMID- 2307803 TI - Hypothesis and case reports: possible thiamin deficiency. AB - Three family members are reported with functional symptoms considered to be caused by intracellular deficiency of thiamin. Persistence of desaturation of erythrocyte transketolase in the face of megadose thiamin hydrochloride (THCl), accompanied by a balanced multivitamin and mineral formula, suggested a familial thiamin dependency state. Each of three individuals responded clinically to the administration of thiamin tetrahydrofurfuryl disulfide (TTFD), and erythrocyte transketolase (TKA) became fully saturated with thiamin pyrophosphate (TPP). Dysautonomic symptoms observed are compared with those seen in classical beriberi, the nutritional prototype for dysautonomia, and changes in blood pressure are described which support this premise. Although there is no proof from the laboratory, it is hypothesized that the biochemical lesion might be due either to malabsorption of thiamin or its inadequate phosphorylation. PMID- 2307804 TI - Nutrition and aging: nutritional status of "apparently healthy" elderly (Dutch nutrition surveillance system). AB - In a nationwide survey the nutritional status was assessed of 539 apparently healthy, independently living elderly aged 65-79 years. Anthropometric data showed no energy deficits. The prevalence of anemia was 4 and 1% among men and women, respectively. Many elderly showed a low level of 25-hydroxyvitamin D in plasma (less than 31 nmol/L: men 35%; women 43%), indicating a marginal status. Although the prevalence of low blood levels of folate, pyridoxal-5'-phosphate, and total carotenoids was higher among the elderly than among younger adults, clear (clinical) signs of nutritional deficiencies were not observed. Prevalence of obesity (13%), hypercholesterolemia (38%), and hypertension (63%) was found to be high, the percentages being higher for women than for men. Several indicators of the nutritional status appeared to differ among age groups. It is concluded that few differences can be considered as being due to physiological aging, which finding should be reflected in reference values for elderly people. PMID- 2307805 TI - Effect of increased dietary calcium on the development of reduced renal mass saline hypertension in rats. AB - A diet fortified with calcium carbonate has been reported to reduce blood pressure in low-renin and salt-sensitive hypertensive patients. We have therefore examined the effect of increased dietary calcium on the development of reduced renal mass-saline hypertension in rats, a classical, low-renin, volume, and sodium-dependent model of hypertension. Rats with 70-75% reduction in renal mass were divided into experimental and control groups. The experimental rats were fed a sodium-free diet supplemented with calcium carbonate (2.0% calcium) and drank 1% saline for 5 weeks. Control rats consumed the salt-free diet and drank 1% saline for the same period. In control rats, as previously observed, blood pressure progressive increased from a control value of 120.0 +/- 1.2 to 174.2 +/- 1.2 mm Hg by the fifth week. In contrast, in the calcium-supplemented rats the development of hypertension was significantly attenuated; the blood pressure only increased from 117.0 +/- 1.2 to 134.0 +/- 3.8 mm Hg by the fifth week. This was associated with a 30% decrease in saline intake by the fifth week, with proportionate decreases in urine volume and sodium excretion but not potassium excretion. Urinary magnesium excretion increased. No such changes were seen in control rats. At the end of the treatment period, plasma levels of sodium, potassium, calcium, creatinine, BUN, and protein were not different, but plasma chloride and magnesium were lower in experimental rats; vascular smooth muscle cell membrane potentials were also not different. These data show that dietary calcium carbonate can attenuate the development of reduced renal mass-saline hypertension in the rat, possibly in part by altering sodium and water intake. PMID- 2307806 TI - Similarity assessment and attribute scaling of sucrose and aspartame in grape drink. AB - The present study investigated the perception of sweetness of aspartame in comparison to various concentrations of sucrose. Twenty-seven subjects were randomly assigned to taste a chilled or room temperature Kool-Aid beverage sweetened with either aspartame or five different concentrations of sucrose. Subjects assessed the perceived similarity in sweetness of an aspartame-aspartame pair and five different aspartame-sucrose pairings and rated each beverage on five bipolar adjectives. Analysis of the similarity ratings revealed that subjects did not perceive the pairs of beverages to differ in perceived sweetness. Analysis of the adjective ratings revealed that aspartame and the lower sucrose concentrations were perceived as being less sweet and more sour than the higher sucrose concentrations. PMID- 2307807 TI - Effects of hypomagnesemia on reactivity of bovine and ovine platelets: possible relevance to infantile apnea and sudden infant death syndrome. AB - Blood platelet function and possible involvement in death of hypomagnesemic ruminants was investigated with 26 Angus cows, 15 mature Hampshire wethers, eight Finnish-Hampshire ewes, and 36 growing Dorset lambs. Hypomagnesemia was induced by feeding vegetative spring tall fescue to 13 cows and semipurified diets low in Mg to nine wethers, four ewes, and 18 lambs. In comparison with controls, dietary treatments reduced plasma Mg concentrations 55% in cows, 36% in wethers, 66% in ewes, and 78% in lambs. Hypomagnesemia reduced in vitro reactivity of cow and lamb platelets to thrombin, ADP, and platelet active collagen, but in vitro tests may not accurately reflect in vivo platelet reactivity. Microscopic examination of platelet-rich plasma revealed a threefold increase in clumped platelets from four hypomagnesemic ewes compared to four normomagnesemic ewes. This suggests that in vivo activation and exhaustion of platelets may have contributed to reduced in vitro platelet reactivity. Six of 18 hypomagnesemic lambs died spontaneously in tetany after 2-12 months on low-Mg diets. Heart and lung lesions were markedly similar to pathological changes induced in other lambs by intravascular activation of platelets with 500 micrograms of vascular collagen fibrils per kg body weight injected intravenously. These results suggest the possibility of abnormal blood platelet activation as a significant mortality risk factor in severe hypomagnesemia. PMID- 2307808 TI - Update: mechanisms by which magnesium modulates intracellular potassium. PMID- 2307810 TI - Organic foods: are they better? PMID- 2307809 TI - Increased contribution of protein oxidation to energy expenditure in head-injured patients. AB - Six patients with acute head injury (initial GCS 4.8 +/- 1.7) were studied to determine the contribution of protein oxidation to resting energy expenditure (REE). Patients were studied on the second or third day post-injury and prior to implementation of nutritional support. Variables measured included REE by indirect calorimetry (normalized to percent predicted energy expenditure calculated from the Harris-Benedict equation). 24-hr urinary nitrogen excretion, calorie, and nitrogen intake. All patients received dexamethasone (39 +/- 2 mg/day) and three received pentobarbital. Mean REE was widely variable, ranging from 43 to 128% of predicted (mean, 90 +/- 31%). Mean 24-hr urinary nitrogen excretion was 16.5 +/- 5.8 g. The contribution of protein oxidation to REE was 30 +/- 4%. The contribution of protein oxidation to REE did not parallel REE (r = 0.237, p = NS) or REE expressed as percent predicted (r = -0.258, p = NS). The contribution of protein oxidation to energy expenditure is greater in acute heat trauma than previously described soft tissue injury and sepsis. The observed excessive nitrogen catabolism and increased contribution of protein oxidation to resting energy expenditure suggest accentuated protein requirements in respect to energy needs in head-injured patients. PMID- 2307811 TI - Organic apple juice no antidote for alar. PMID- 2307812 TI - Communicating the concepts of good nutrition in the 1990s. PMID- 2307813 TI - Daily intakes of nine nutritional elements: analyzed vs. calculated values. AB - The daily intakes for eight age-sex groups (infants, young children, and male and female teenagers, adults, and older adults) of nine nutritional elements (sodium, potassium, calcium, phosphorus, magnesium, iron, zinc, copper, and manganese) were obtained by laboratory analysis of the Food and Drug Administration's 234 Total Diet Study (TDS) foods and by use of the USDA Nutrient Data Base for Standard Reference. Food substitutions were required for eight TDS foods that had no direct counterparts in the USDA database. When corrections were made for missing values for magnesium, zinc, copper, and manganese in the USDA database, average percent differences between the two methods (USDA-TDS) for the age-sex groups were -2.6 for iron, 0.6 for manganese, 0.9 for zinc, 5 for potassium and phosphorus, 7 for magnesium, 8 for sodium and calcium, and 11.0 for copper. Data in the USDA database (when corrected for missing values) provided estimates of daily intakes of nine nutritional elements that were similar to those obtained by use of data from laboratory analysis in the TDS. PMID- 2307814 TI - Accuracy of visual estimates of plate waste in the determination of food consumption. AB - A six-point visual estimation scale developed by Comstock was used by qualified dietitians to rate amounts of 978 servings of 117 different food items remaining as plate waste. Consumption of the food items was estimated as the difference between the weight of a randomly selected full serving of each item and the score on the visual estimation scale, which had been expressed as a proportion of that full-serving weight. The bias of the visual estimates averaged 2.2 gm; their imprecision averaged 13.7 gm. The small amount of bias in these estimates only slightly influences the results of studies using them as a substitute for weighed data. However, the much larger amount of imprecision must be accounted for. Sample size requirements for the detection of a statistically significant difference in food consumption between two or more groups using visual estimates of plate waste will be greater than those required when exact weighing techniques are used. In addition, the accuracy of dietary self-report data will be underestimated when such visual estimates are used as criterion measures of food consumption unless statistical adjustments are made to correct for the impact of the documented imprecision. PMID- 2307816 TI - Anthropometric measurements of white and black southern adolescent girls. AB - Anthropometric measurements of 691 white and 550 black 12-, 14-, and 16-year-old girls from three income groups, residing in the southern United States, were evaluated, Heights, weights, mid-upper arm circumferences, and arm muscle areas of 14-year-old girls were significantly higher than those of 12-year-old girls and significantly lower than those of girls 16 years of age; triceps skinfolds, arm fat areas, and body mass indexes of 12-year-olds were significantly lower than those of older subjects. Blacks had significantly higher weights, body mass indexes, and arm muscle areas than whites. Black 12-year-old girls were significantly taller than white 12-year-old girls but significantly shorter than older girls of either race; white 16-year-old girls were significantly taller than blacks of that age. Body mass indexes of black 12-year-olds and white 14 year-olds were significantly higher than those of white 12-year-olds, and significantly lower than those of black 14- and 16-year-olds. Medium-income blacks and whites of all income levels had lower (usually significantly) weights, body mass indexes, mid-upper arm circumferences, arm muscle areas, and arm fat areas than low- and high-income blacks did. Anthropometric values of white, but not of black, girls were generally similar to those reported in surveys of primarily white girls. PMID- 2307815 TI - An evaluation of food group intakes by Mexican-American children. AB - Food group daily servings were examined for 3,436 children who participated in the Mexican-American portion of the 1982-1983 Hispanic Health and Nutrition Examination Survey (HHANES). Mean daily servings of 40 foods and food groups were calculated for four age groups: 1 to 2 years, 3 to 5 years, 6 to 11 years, and 12 to 17 years. The HHANES food servings data were combined into four major groups and compared with recommended servings for children. Mean daily servings of the milk group exceeded the recommended two to three servings for younger children but were low for teenagers. Meat group servings (including eggs and nuts/legumes) exceeded the recommended two daily servings for all age groups, whereas bread group intakes averaged 70% to 80% of a recommendation of four servings but only half of a recommendation of six servings. Intakes of fruits and vegetables were lowest, averaging only 33% to 47% of a recommended four servings, or 26% to 38% of a recommended five servings. Servings of all four groups were lowest for teenagers. A dietary score, based on the number of servings from each of the four groups, was developed for each child. Mean dietary scores ranged from 55% (teenagers) to 70% (toddlers and preschoolers) of the recommended score. According to these analyses, dietary guidance for Mexican-American children should focus on increasing intakes of fruits and vegetables and on encouraging more nutritious food choices by teenagers. PMID- 2307817 TI - Dietary assessment in children using electronic methods: telephones and tape recorders. AB - Selection of dietary assessment methodology is important in dietary intervention studies. Few studies have reported the relative merits of various assessment methods or the feasibility of electronic methods in pediatric populations. Parent child dyads performed telephone recalls (no. = 32) and tape recorded dietary records (no. = 33). Traditional recalls were first conducted to familiarize parents and children with the telephone recall procedure, to introduce two dimensional food models, and to instruct on the use of the tape recorder. Parents monitored and documented as unobtrusively as possible the child's intake on the day before the telephone recall and also on the day of the taped record. Children were called at random to reduce bias. Simple correlation coefficients (r) were calculated for nine nutrients and calories for both methods. For telephone recalls, values ranged from a low of r = .64 for saturated and polyunsaturated fat to r = .85 for cholesterol and r = .93 for iron. Tape-recorded data yielded r = .80 or above, except calories with r = .68 (p less than .001 for all values, 1 tail tests). Mean nutrient values were within expected ranges, e.g., 1,800 kcal +/- 500, with saturated fat about 14% of calories per day. Comparisons between parents and childrens reports of food frequencies and portion sizes revealed the best correlations for beverages, bread-cereals-crackers, meat-fish-poultry, and mixed dishes. We conclude that preadolescent children are able to provide dietary intake data using electronic methods in a manner that compares favorably with their parents' written records. PMID- 2307818 TI - Client perceptions of dietetic students and registered dietitians at a university based nutrition clinic. AB - Client perceptions of students enrolled in a nutrition counseling practicum were compared with client perceptions of those students' clinical instructors, who were registered dietitians. One hundred forty-two clients who had either a student (no. = 81) or a dietitian (no. = 61) as primary counselor completed a postcard evaluation or a telephone interview. Students were rated significantly more positively (p less than .01) than their instructors for the item "I would recommend the clinic to others" and (p less than .05) for the items "The counselor helped me with my problem" and "I learned at the clinic what I did not know before." Seventy-two of the 89 clients interviewed by telephone replied to the question "Did students enhance or detract from services provided?" Sixty-one percent replied that students enhanced, but 25% replied that students detracted in some way, primarily because of concerns about having an additional observer during counseling sessions. In general, clients receiving nutrition counseling evaluated student dietitians very positively. PMID- 2307819 TI - Food choices of Air Force Academy cadets as reflected by the Food Choice Inventory. PMID- 2307820 TI - Self-reports of salt intake by 10- to 18-year-olds: relationship to urinary sodium excretion. AB - Our data indicated that self-reports of consumption of salty foods by children and adolescents were associated with 24-hour urinary sodium excretion. Specifically, youths 10 to 18 years of age who selected a poster depicting high sodium foods excreted significantly more sodium than youths who selected a poster depicting low-sodium foods. Future research is needed to refine simplified self report measures, to corroborate the validity of the measures, and to extend the studies to other samples, e.g., younger children. PMID- 2307821 TI - Vitamin and mineral supplement use by women with school-age children. PMID- 2307822 TI - Factors affecting the dietary habits of adolescents with cystic fibrosis. PMID- 2307823 TI - Acceptance and consumption of crystalline fructose menu items by institutionalized elderly persons. PMID- 2307824 TI - Evaluation of a new nutritional supplement for patients with Alzheimer's disease. PMID- 2307825 TI - Serum concentrations of the carboxyterminal cross-linking domain of procollagen type IV (NC1) and the aminoterminal propeptide of procollagen type III (PIIIP) in chronic liver disease. AB - Serum concentrations of both the carboxyterminal cross-linking domain (NC1) of procollagen type IV and the aminoterminal propeptide of procollagen type III (PIIIP) were measured by specific radioimmunoassays in 60 patients with chronic liver disease and 50 healthy controls. Compared with controls (5.3 +/- 1.3 ng/ml, mean +/- S.D.), NC1 concentrations were significantly elevated in patients with chronic active hepatitis (10.2 +/- 2.0 ng/ml) and liver cirrhosis (13.5 +/- 3.0 ng/ml), but not in chronic persistent hepatitis (6.0 +/- 0.9 ng/ml). The concentrations in patients with active liver cirrhosis were significantly higher than those in patients with inactive cirrhosis. Serum concentrations of PIIIP in controls, parients with chronic persistent hepatitis, chronic active hepatitis and cirrhosis were 5.8 (4.3-7.9), 5.3 (3.5-7.9), 17.5 (10.6-28.9), 16.7 (10.4 26.7) ng/ml, respectively (logarithmic mean and range of mean +/- S.D. after retransformation). Patients with liver cirrhosis had significantly higher concentrations of NC1 in serum than those with chronic active hepatitis, but there was no difference in serum PIIIP concentrations between the two groups. These data suggest an alteration of type IV collagen metabolism in chronic liver disease. In liver cirrhosis, the metabolism of collagen IV is apparently different from that of collagen type III; serum NC1 determinations may therefore provide additional information on chronic liver disease, particularly in patients with cirrhosis with a normal level of serum PIIIP. Further follow-up studies as well as investigations related to the basic mechanism of the elevation of these peptides in serum are needed in order to understand their clinical significance fully. PMID- 2307826 TI - Diffuse biliary tract involvement mimicking primary sclerosing cholangitis after bone marrow transplantation. PMID- 2307827 TI - Acute exacerbations in Chinese patients with chronic hepatitis B virus (HBV) infection. Incidence, predisposing factors and etiology. AB - Three hundred and eighty-six Chinese patients (262 men and 124 women), age 5-74 years, with chronic hepatitis B virus (HBV) infection were prospectively followed for 1-5 years to determine the incidence, predisposing factors and etiology of acute exacerbations that occurred during the course of chronic HBV infection. Group I consisted of 334 patients with serum alanine aminotransferase (ALT) levels below 200 IU/l at presentation. Of these, 29 (8.7%) patients developed 32 episodes of acute exacerbation during follow-up. The cumulative probabilities of developing exacerbations were 6.3% and 15% at the end of 1 and 4 years, respectively. Group II included 52 patients with ALT levels above 200 IU/l at presentation. Of these, 19 (37%) patients developed 26 episodes of exacerbation during follow-up. The cumulative probabilities of developing eacerbations were 24% and 47% at the end of 1 and 4 years, respectively. In both groups, the probability of developing exacerbations was slightly higher in men and significantly higher in those above the age of 20 and those who were HBeAg positive. Logistic regression analysis showed that HBeAg positivity (p less than 0.00001), elevated ALT levels (greater than 200 IU/l) at presentation (p less than 0.0001) and male sex (p = 0.03) were associated with a significantly higher probability of developing exacerbations. Twenty eight (48%) episodes of exacerbation were accompanied by symptoms of acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307828 TI - Increase in the relative amount of bilirubin diconjugates in rat bile and serum under infusion of phthaleins and indocyanine green. AB - The effect of organic anions on bilirubin metabolism and excretion was investigated in rats. Biliary excretion of bromosulfophthalein, bromcresol green and indocyanine green led to a significant decrease in excretion of bilirubin pigments and to an increase of their concentration in serum. This was concomitant with a marked increase in the ratio of bilirubin diconjugates to monoconjugates in bile and serum. These changes were unrelated to either bile flow, biliary lipid output, or hepatic activity of bilirubin UDP-glucuronyl transferase. Following bolus injection of [14C]bilirubin, peak excretory rate of radioactivity was markedly delayed in rats infused with bromosulfophthalein, as compared to controls. It is concluded that administration of the organic anions increased the ratio of bilirubin diconjugates to monoconjugates in bile and serum, by slowing down the intrahepatic transit of bilirubin pigments. This, in turn, allowed more efficient enzyme-catalyzed formation of bilirubin diconjugates from the intermediate bilirubin monoconjugates. PMID- 2307829 TI - Acute hepatitis delta virus superinfection in patients with liver cirrhosis. AB - A clinicopathologic study in a total of 164 patients with acute hepatitis delta virus (HDV) infection showed that nine male patients (5.5%) had evidence of liver cirrhosis prior to or during the episode of acute hepatitis. All nine patients had typical clinical presentations and laboratory findings of acute viral hepatitis. Four of them had prolonged prothrombin time, three developed ascites and one finally died of hepatic failure. Clinical ascites occurred more frequently in cirrhotic patients with severe but non-fulminant hepatitis than their non-cirrhotic counterparts (p less than 0.05). In addition, histologic studies in five patients with cirrhosis disclosed diffuse lobular necrotizing inflammatory activity, with four showing bridging hepatic necrosis, which also occurs more frequently in cirrhotic than in non-cirrhotic patients (p less than 0.05). The data suggest that HBsAg positive patients with cirrhosis are susceptible to acute HDV infection which may lead to extensive necrosis or even decompensation and failure, simulating decompensation of the underlying liver disease. Therefore, careful clinicopathologic work-ups are required for accurate diagnosis and correct assessment of their outcomes. PMID- 2307830 TI - Glucagon increases hepatic efficacy for urea synthesis. AB - The effect of glucagon on the relation between urea synthesis and blood amino acid concentration was studied in seven healthy volunteers. Alanine was given as prime-continuous infusions and, after 1 hr for equilibration, the urea nitrogen synthesis rate was measured in two periods of about 2 hrs as urinary excretion corrected for accumulation and intestinal hydrolysis. During one of the periods, glucagon was infused to obtain a constant concentration of 200-1200 ng/l. The spontaneous urea synthesis during the alanine infusion was 86-141 mmol/hr and linearly related to the alanine concentrations of 1.33-2.99 mmol/l. The hepatic clearance of alanine-nitrogen to urea-nitrogen, assessed by the ratio between the increase in the urea synthesis rate and alanine concentration, was 23 +/- 4 l/hr (mean +/- S.D.). Glucagon increased the rate of urea synthesis by 35 +/- 11 mmol/hr (p less than 0.02) and decreased the alanine concentration by 0.22 +/- 0.06 mmol/l (p less than 0.01). Glucagon increased the hepatic nitrogen clearance to an average of 42 +/- 13 l/hr (p less than 0.01). The difference between infusion of amino-nitrogen and appearance of urea-nitrogen was +15 +/- 10 mmol/hr during alanine infusion alone and -11 +/- 25 mmol/hr during exogenous glucagon. The loss of nitrogen could be accounted for by depletion of non-alanine amino acids from the blood. Glucagon increases the efficacy of urea synthesis, which may be of importance for catabolism by changing the hepatic contribution to nitrogen homeostasis. PMID- 2307831 TI - Diclofenac associated hepatitis. AB - Diclofenac is a widely used non-steroidal anti-inflammatory drug, being the most commonly prescribed of its kind in the world. This paper describes five cases of hepatitis with clinical features indicating a direct link with diclofenac. All the patients presented with an acute hepatitis, three being jaundiced. They gave a history of taking diclofenac up to the time of presentation, four of the five having started the drug within the previous 3 months. There were no other features in the histories to suggest alternative causes for the liver dysfunction. Liver function tests were grossly abnormal in all cases, showing a hepatitic picture. A liver biopsy was performed in 4 cases, and showed features of an acute hepatitis with inflammation and hepatocyte damage dominating. The liver dysfunction returned to normal on drug withdrawal in four of the five cases, with full recovery by 3 months. One patient developed steroid-responsive chronic active hepatitis. Hepatotoxicity associated with diclofenac is documented, but previously only a few isolated cases have been described. The occurrence of five cases in one gastroenterology unit over a 12-month period suggests that hepatitis associated with diclofenac may be commoner than previously supposed. PMID- 2307832 TI - Immunization in adults I. PMID- 2307833 TI - The Ba fragment of complement factor B inhibits human B lymphocyte proliferation. AB - Normal human B lymphocyte function is finely regulated by both positive and negative signals at each stage of activation, proliferation, and differentiation. Activation signals include antigen and surface Ig cross-linking agents such as anti-mu or anti-delta. Signals inducing proliferation include IL-2, high m.w.-B cell growth factor (BCGF), and low m.w.-BCGF. IL-2 as well as IL-6 and other partially characterized B cell differentiation factors can induce terminal differentiation of proliferating B cells into Ig-secreting plasma cells. Various C components have been described to regulate B cell function including Bb that enhances proliferation, C5a that enhances Ig production, and C3a that inhibits Ig production. In our study, we examined the ability of the factor B cleavage fragment Ba to influence human B cell function. Ba did not affect the activation of resting B cells but inhibited the proliferation of activated B cells stimulated with either high m.w.-BCGF or low m.w.-BCGF. The inhibition occurred with doses of Ba as low as 1 microgram/ml (29 nM). Ba was found to bind to activated human B lymphocytes in a saturable manner with an apparent K of approximately 25 nM and an apparent Bmax of 56,000 sites/cell. A peptide made of the carboxy terminal 10 amino acids of Ba (GHGPGEQQKR), was also found to inhibit growth factor induced proliferation of activated B cells but at an ID50 of approximately 5 microM. Finally, Ba was found to inhibit the terminal differentiation of Staphylococcus aweus Cowan-activated B cells stimulated with B cell differentiation factors but not Ig secretion by the partially differentiated EBV-transformed cell line SKW.6. Thus, concentrations of Ba achievable in vivo at sites of active inflammation were found to act on human B lymphocytes by inhibiting their proliferation. This may act to limit the immune response to a specific antigenic challenge. PMID- 2307834 TI - Antigen presentation by resting B cells. Effectiveness at inducing T cell proliferation is determined by costimulatory signals, not T cell receptor occupancy. AB - Resting B cells stimulated the proliferation of two T cell clones much less efficiently than T cell-depleted low-density APC. In contrast, low-density cells and resting B cells stimulated the clones to produce similar levels of inositol phosphates, a rapid biochemical event dependent only on occupancy of the TCR. The inefficient stimulation of T cell proliferation by resting B cell APC was dramatically improved by the addition of allogeneic low-density accessory cells incapable of being recognized by the TCR on the responding T cells. The results are most consistent with a model where low-density and resting B cell APC display similar amounts of Ag/Ia molecule complexes capable of being recognized by the TCR on the responding T cells but differ in the provision of costimulatory signals that, together with TCR occupancy, are required for IL-2 production. PMID- 2307835 TI - Constitutive competition by self proteins for antigen presentation can be overcome by receptor-enhanced uptake. AB - The cells recognize a bimolecular ligand composed of a self Ia molecule and a fragment of foreign Ag that has been processed by an APC. The effect of self proteins on the processing and presentation of foreign Ag was examined in order to ascertain the mechanisms for competition between foreign and self Ag. How this competition can be overcome to allow an efficient immune response was also examined. Normal mouse serum proteins (NMS) compete for the processing and presentation of the foreign Ag bovine RNase by APC. This competition could have occurred at any of three levels in the APC: 1) Ag uptake, 2) Ag processing, or 3) the binding of Ag to an Ia molecule. No competition for either the uptake or the processing of RNase by self proteins could be demonstrated. However, self peptides do compete with foreign Ag by binding directly to Ia molecules, as has been shown previously. Thus, the observed inhibition by NMS of Ag presentation occurred because of competition for binding to the Ia molecule. We hypothesized that during the generation of an immune response this competition is overcome by enhanced uptake of foreign Ag. To test this, we compared the ability of NMS to compete for the presentation of RNase when it entered the APC via fluid-phase pinocytosis or through receptor-mediated uptake via the mannose receptor. When the RNase entered the APC through the mannose receptor, the ability of NMS to compete was dramatically reduced. Thus, self proteins constitutively compete for the presentation of foreign Ag at the level of binding to an Ia molecule, and this competition can be overcome by receptor-mediated uptake of the Ag. PMID- 2307836 TI - Anti-CD9 monoclonal antibodies induce homotypic adhesion of pre-B cell lines by a novel mechanism. AB - Anti-CD9 mAb are known agonists of platelet aggregation, but have not been implicated in cell-cell adhesion. We show here in an experimental system that the anti-CD9 mAb 50H.19, ALB6, and BA-2 can induce rapid, and irreversible, homotypic aggregation of the CD9-positive pre-B lymphoblastoid cell lines NALM-6 and HOON, but not of the CD9-negative B cell line Raji. The specificity of the response is indicated by the failure to effect aggregation with mAb directed to CD24, or to HLA class I Ag. The initiation of strong homotypic aggregates of lymphoid cells is a property ascribed to lymphocyte function-associated Ag-1 (LFA-1), a member of the beta 2 subfamily of leukocyte integrins. We show that CD9-induced aggregation is an active process which proceeds at 37 degrees C, but not at 4 degrees C, requires the expenditure of metabolic energy, and a functioning cytoskeleton, and is not inhibited by Arg-Gly-Asp-Ser peptide. These are properties described for LFA-1-mediated aggregation. However, because beta 2 integrins are not expressed on NALM-6 or HOON cells, they are not the mediators of CD9-induced aggregation. In contrast to LFA-1-mediated adhesion which is Mg2+ dependent, CD9-induced adhesion has an absolute requirement for Ca2+, but not Mg2+, indicating that a Ca2(+)-dependent event is sufficient for adhesion. However, Mg2+ enhances adhesion even at optimal concentrations of Ca2+, implicating an additional Mg2(+)-dependent event which requires Ca2+ to be effective. These findings suggest that CD9 Ag regulates a novel mechanism for promoting tight cell-cell adhesion which requires both Ca2+ and Mg2+ for optimal expression. PMID- 2307837 TI - Both ongoing suppression and clonal elimination contribute to graft-host tolerance after transplantation of HLA mismatched T cell-depleted marrow for severe combined immunodeficiency. AB - Lymphocytes from children with severe combined immunodeficiency who had been immunologically reconstituted with haploidentical T cell-depleted bone marrow were analyzed with regard to their immunologic recognition of donor, host, or third party alloantigens. When compared with freshly isolated donor lymphocytes, the engrafted donor cells exhibited markedly reduced to absent responses toward host Ag in primary or secondary MLC and cell-mediated lympholysis assays. However, under limiting dilution conditions, cytotoxic responses to host Ag could be demonstrated, indicating that small numbers of host reactive cells were present, although down-regulated at high responder cell doses. These results are consistent with prior observations in limiting dilution cultures that indicate that cells with the potential to lyse autologous target cells exist in the peripheral blood of all normal individuals. The number of host reactive cells present in these patients is significantly less than that present in cells isolated directly from the marrow donors, and is also less than the number of autocytotoxic cells normally seen in peripheral blood. Together, these observations indicate that two mechanisms contribute to donor host tolerance in these patients. The majority of host reactive cells appear to have undergone clonal deletion or inactivation, whereas the small residual host-reactive population appears to be under ongoing immunoregulatory control. PMID- 2307838 TI - Autoantibodies to aminoacyl-transfer RNA synthetases for isoleucine and glycine. Two additional synthetases are antigenic in myositis. AB - Autoantibodies to three of the aminoacyl-transfer RNA (tRNA) synthetases have been reported (for histidine, threonine, and alanine). Most patients with these autoantibodies have polymyositis, and the majority also have interstitial lung disease. This study examined the question of whether autoantibodies to other aminoacyl-tRNA synthetases occur in the sera of myositis patients. We tested sera from patients with myositis with unidentified anticytoplasmic antibodies that immunoprecipitate tRNA for the ability to inhibit the aminoacyl-tRNA synthetases for the remaining 17 amino acids. Three sera showed strong inhibitory activity for a synthetase. OJ and NJ sera (and IgG) significantly inhibited isoleucyl-tRNA synthetase activity, each with 94% inhibition at the screening dilution, whereas other test sera and controls all inhibited less than 50%. OJ and NJ sera immunoprecipitated identical patterns of tRNA, and identical, complex patterns of high m.w. polypeptides that were consistent with the multienzyme synthetase complex of which isoleucyl-tRNA synthetase is a part. EJ serum (and IgG) significantly inhibited glycyl-tRNA synthetase, and immunoprecipitated a unique pattern of transfer RNA, and a strong predominant protein band of 77 kDa. These data strongly suggest that OJ and NJ have autoantibodies to isoleucyl-tRNA synthetase, and that EJ has antibodies to glycyl-tRNA synthetase. The findings of signs of muscle involvement in all three patients, and severe interstitial lung disease in OJ, strengthens the association of antisynthetases with these conditions. PMID- 2307839 TI - Effects of recombinant murine tumor necrosis factor-alpha on immune function. AB - TNF-alpha is a macrophage-derived cytokine with diverse biologic activities, including potent immunomodulatory effects. In vitro studies have implied that TNF alpha has predominantly proinflammatory and immunostimulatory effects, but paradoxically in vivo studies have demonstrated that administration of TNF-alpha suppresses murine lupus. To assess the effects of TNF-alpha on immune function in normal mice, we treated C57BL/6 mice with recombinant murine TNF-alpha (10 micrograms i.p.) or PBS on alternate days for up to 8 wk. Administration of TNF alpha decreased the percentage of splenic T and B cells and increased the percentage of splenic macrophages without significantly altering the total number of mononuclear cells. Administration of TNF-alpha also caused progressive inhibition of splenic lymphocyte function, out of proportion to the quantitative reduction in B and T cells. After 8 wk of therapy, the proliferative responses of splenic lymphocytes to Con A, PHA, and LPS were reduced by 100, 90, and 60%, respectively, in treated mice compared with control mice. The reduction in T cell proliferation was due primarily to alteration of accessory cell function rather than direct inhibition of T cell function. Treatment with TNF-alpha markedly inhibited T cell cytotoxicity induced by immunization with allogenic target cells, and it virtually ablated NK cell activity. Inhibition of these in vitro tests of lymphocyte function correlated with inhibition of delayed type hypersensitivity in vivo. In contrast, treatment with TNF-alpha did not impair humoral immunity. These findings imply that TNF-alpha may affect cell-mediated immunity more profoundly than humoral immunity. This observation may be relevant to the mechanism whereby TNF-alpha suppresses murine lupus. PMID- 2307840 TI - IL-3-induced activation of protein kinases in the mast cell/megakaryocyte R6-XE.4 line. AB - A role for second messenger-regulated protein kinases in the early post-IL-3 receptor signal transduction pathway was investigated in the mast cell/megakaryocyte line R6-XE.4. The activity of the calcium- and phospholipid dependent protein kinase C (PKC) was assessed by the ability of the enzyme to phosphorylate histone H1 in the presence of calcium, diacylglycerol, and phosphatidylserine or after proteolytic activation of PKC with trypsin. In high serum-supplemented cells, but not in cells that were preincubated in serum deficient media for 6 h, subsequent treatment for 15 min with synthetic IL-3 (10 micrograms/ml) caused up to a sixfold increase in the calcium- and lipid stimulated histone H1 phosphorylating activity of particulate-associated PKC after fractionation on MonoQ. However, there was no corresponding reduction of cytosolic PKC activity. Therefore, IL-3 appeared to modify the activity of preexisting membrane-associated PKC rather than eliciting its recruitment from the cytoplasm in R6-XE.4 cells. This was in contrast to the situation with FDC-P1 cells, where IL-3 induced PKC translocation. IL-3 also stimulated a cytosolic protein kinase that phosphorylated a synthetic peptide patterned after a phosphorylation site in ribosomal protein S6, but this IL did not alter the activity of cAMP-dependent protein kinase. PMID- 2307841 TI - The human lung fibroblast cell line, MRC-5, produces multiple factors involved with megakaryocytopoiesis. AB - The human lung fibroblast cell line MRC-5 constitutively produces a megakaryocyte potentiator activity, identified in murine bone marrow liquid culture assays for acetylcholinesterase and megakaryocyte colony assays in the presence of low concentrations of IL-3. The production levels of this activity were increased after stimulation with the phorbol ester analog, mezerein, and the calcium ionophore, A23187. Complete purification of a protein having this activity from conditioned media of induced MRC-5 cells was achieved using gel filtration and ion exchange chromatography. The first 14 residues of the purified protein identified by amino-terminal sequencing were identical to the first 14 residues of IL-6. Recombinant human IL-6 was tested and found to promote megakaryocyte growth. IL-1 beta, another component detected in MRC-5 conditioned media, was unable to promote megakaryocyte colony formation but did reduce the concentration of IL-6 necessary to support megakaryocyte colony formation. Immunoprecipitation using rabbit antiserum prepared against IL-6 removed the megakaryocyte growth activity found in MRC-5 conditioned media. Thus, connective tissue cells such as fibroblasts in the bone marrow may co-stimulate thrombocytopoiesis via IL-6 and, possibly, via IL-1 production. PMID- 2307842 TI - Purification of 1F5 antigen that prevents complement attack on homologous cell membranes. AB - A mAb, 1F5, has the ability to cause hemolysis by human serum of human E treated with neuraminidase via the alternative C pathway. By Western blotting, this mAb reacts with a glycoprotein having a molecular mass of 20 kDa (1F5Ag). 1F5Ag was isolated from human E by affinity chromatography with mAb-coupled Sepharose. Purified 1F5Ag was then adsorbed to guinea pig E rendering them resistant to human C attack by both the classical and the alternative pathways. Furthermore, experiments with isolated C components revealed that 1F5Ag interferes with both homologous human C8 and C9 in the terminal stage of the C reaction, whereas it has little effect on hemolysis by rabbit C8 and C9. Therefore, 1F5Ag can be called HRF20, which stands for homologous restriction factor of 20 kDa. PMID- 2307843 TI - On the dissociation and reassociation of MHC class II-foreign peptide complexes. Evidence that brief transit through an acidic compartment is not sufficient for binding site regeneration. AB - The stability of a specific complex between the peptide Ag representing residue 323-339 of OVA and the MHC class II protein, I-Ad, in a lipid bilayer was investigated as a function of pH and temperature. The complex is much more stable in a lipid bilayer than previously reported for detergent micelles. Measureable dissociation was detectable only after several hours at a pH below 5. The results show that a purified preparation of MHC class II molecules can sequentially bind, release, and rebind peptide, indicating that, in principle, MHC class II molecules could be used more than once for peptide binding. However, the time and pH required for peptide-MHC dissociation suggests that, in an Ag presenting cell, either a prolonged residence in an acidic compartment or other factors will be required for regeneration of the peptide binding site. PMID- 2307844 TI - High-affinity binding of an influenza hemagglutinin-derived peptide to purified HLA-DR. AB - Immunogenic peptides have been shown to bind detergent-solubilized class II (Ia) molecules from mice. In this investigation, we report that highly purified HLA-DR (DR) molecules in detergent solution are capable of binding a synthetic peptide (HAp) derived from the influenza hemagglutinin sequence. Although the presentation of this peptide has been demonstrated only to DR1-restricted Th cells, the association rate constants for the formation of HAp-DR1, -DR5, and DR8 complexes were essentially identical (ka = 1.1 x 10(2) to 1.6 x 10(2) M-1 s 1). By contrast, the value of the rate constants for the dissociation of preformed HAp-DR1, -DR5, and -DR8 complexes varied nearly threefold (kd = 1.6 x 10(6) to 4.4 x 10(-6) s-1). The value of the equilibrium dissociation constants (KD) derived from these rate constants were 13 nM, 24 nM, and 28 nM, for HAp-DR1, -DR5, and -DR8 complexes, respectively. Scatchard analysis demonstrated that the KD obtained from the rate constants for the HAp-DR1 reaction was in excellent agreement with that obtained under equilibrium conditions. SDS-PAGE confirmed that the HAp-DR complexes were remarkably stable, as HAp remained associated with the DR alpha beta heterodimer after treatment of the complexes with SDS and beta mercaptoethanol. Steady-state binding studies demonstrated that 18% of all DR1 molecules had bound HAp at equilibrium, whereas only 3.8% of all DR8 molecules had bound HAp under identical conditions. The slight differences in the KD for HAp-DR complexes suggest that differences in the affinity of a peptide for DR alleles alone may not always explain the process of MHC restriction. PMID- 2307845 TI - The THP-1 cell line is a urokinase-secreting mononuclear phagocyte with a novel defect in the production of plasminogen activator inhibitor-2. AB - Mononuclear phagocytes regulate the generation of plasmin by secreting urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-2 (PAI-2). We investigated the production of plasminogen activator (PA) and PA inhibitor by the human monocytic leukemia cell line, THP-1. Similar to U937 monoblast-like cells and peripheral blood monocytes (PBM), THP-1 cells produce a PA that is specifically neutralized by anti-uPA antibody and comigrates with human high molecular mass uPA (54 kDa) on casein-plasminogen zymogaphy. PA activity could be dissociated from intact THP-1 cells by brief treatment with a weak acid-glycine buffer, indicating that the uPA is secreted and bound to receptors on the plasma membrane. Regulation of uPA proceeds normally in THP-1 cells, with cell associated PA activity increasing from 77 +/- 20 to 163 +/- 26 and 325 +/- 30 mPU/10(6) cells in response to PMA and LPS, respectively; parallel increases in steady state levels of uPA mRNA were observed. In contrast to normal expression of uPA activity, functional PAI-2 could not be demonstrated in either the conditioned media or cell lysates of THP-1 under basal or stimulated conditions. Both U937 and PBM secrete low levels of PA inhibitor activity that increase substantially in response to stimulation with PMA and LPS. Immunoreactive PAI-2, measured by ELISA, was undetectable in THP-1 lysates or conditioned medium, but was consistently present in U937 and PBM, paralleling the presence of PA inhibitor activity. THP-1 cells express low levels of an abnormally sized mRNA for PAI-2 and demonstrate a regulatory defect whereby steady state levels of PAI 2 mRNA are markedly reduced upon stimulation with PMA or LPS. By contrast, U937 and PBM respond to identical stimulation with increases in PAI-2 mRNA. We conclude that THP-1 cells express a structurally abnormal species of PAI-2 mRNA, with complete loss of inhibitory activity as well as altered function of PMA- and LPS-responsive regulatory elements. PMID- 2307846 TI - Complement C5a activation of phospholipase D in human neutrophils. A major route to the production of phosphatidates and diglycerides. AB - The contribution of phospholipase D (PLD) to the production of phosphatidic acid (PA) and diglyceride (DG) by C5a-stimulated human neutrophils has been studied. Membrane-associated 1-O-alkyl-phosphatidylcholine (alkyl-PC) was double labeled with 3H and 32P by incubating neutrophils with [3H]alkyl-lysoPC and alkyl [32P]lysoPC. Upon stimulation with recombinant C5a, these labeled neutrophils produce 1-O-alkyl-phosphatidic acid (alkyl-PA) and, in the presence of ethanol, 1 O-alkyl-phosphatidyl-ethanol (alkyl-PEt), containing both 3H and 32P. Formation of radiolabeled alkyl-PEt parallels that of radiolabeled alkyl-PA and requires both extracellular Ca2+ and cytochalasin B. Furthermore, the 3H/32P ratios of alkyl-PA and alkyl-PEt formed during stimulation are very similar to that of th substrate alkyl-PC. These results demonstrate that, in C5a-stimulated neutrophils, alkyl-PA and alkyl-PEt are formed from alkyl-PC almost exclusively by PLD-catalyzed hydrolysis and transphosphatidylation, respectively. Upon C5a stimulation, neutrophils labeled with 3H and 32P also produce 1-O-[3H]alkyl diglyceride [( 3H]alkyl-DG) and [32P]orthophosphate [( 32P]PO4), but not [32P]phosphocholine. [3H]Alkyl-DG and [32P]PO4 are formed in parallel, although temporally lagging behind alkyl-PA. Propranolol, a PA phosphohydrolase (PPH) inhibitor, decreases the formation of both [3H]alkyl-DG and [32P]PO4, although increasing alkyl-PA accumulation. These data support the conclusion that alkyl-DG is formed from alkyl-PC by the combined activities of PLD and PPH and not by phospholipase C (PLC). Furthermore, by using [3H]acyl-PC-labeled neutrophils, it is demonstrated that, like alkyl-PC, 1-acyl-PC is also degraded sequentially by PLD and PPH to 1-acyl-DG. Propranolol does not inhibit phosphoinositide-specific PLC and yet it causes almost complete inhibition of the total DG mass accumulation in C5a-stimulated neutrophils. We conclude that, in cytochalasin B treated neutrophils stimulated with C5a, PLD-catalyzed hydrolysis of PC determines the levels of both PA and DG with potentially important ramifications for neutrophil-mediated defense functions. PMID- 2307847 TI - Identical D region sequences expressed by murine monoclonal antibodies specific for a human tumor-associated antigen. AB - Sequence analysis has revealed significant structural similarities among murine mAb specific for the human tumor-associated Ag GA733. Antibodies generated in independent immunizations, either with Ag-positive tumor cells or with anti idiotypic antibodies produced by immunization of goats with a GA733-specific antibody, all use members of the same gene families; remarkably, they also express identical amino acid sequences in their H chain CDR3. Inasmuch as this region normally exhibits considerable sequence variability, the identity displayed by the antibodies indicates a requirement for this particular sequence in the generation of their specificity for the GA733 antigen. Moreover, this homology suggests that the antibodies recognize a common determinant on the Ag, and that the polyclonal anti-idiotypic antibodies can functionally mimic the Ag at the level of the structure of the Ag-specific antibody that is induced. PMID- 2307848 TI - The murine complement receptor gene family. III. The genomic and transcriptional complexity of the Crry and Crry-ps genes. AB - The murine CR genes Crry (previously termed mCRY) and Crry-ps (previously termed mCRX) are two distinct, but related, sequences which are the evolutionary homologs to sequences contained within the human CR1 gene. Screening a BALB/c genomic DNA library with the Crry/Crry-ps specific cDNA resulted in the isolation of two clusters of genomic sequences: those specific for Crry and those specific for Crry-ps. The coding sequences of the Crry gene encompass over 25 kb of DNA, whereas the Crry-ps sequences are included within a single 5.6-kb Eco-R1 fragment. The Crry gene consists of 10 separate exons. The first of these contains both the signal sequence and an alternatively spliced 129 bp present in approximately 10% of the Crry transcripts. Of the remaining exons, two encode a single sixty amino acid repeat domain each (A and E), two encode a split sixty amino acid repeat (B), and another encodes two 60 amino acid domains (C and D) fused as one exon. The transmembrane and cytoplasmic regions are both split into two exons each. RNA protection analysis indicates that although there is alternative splicing in the 5' region of the gene, the 3' exons encoding the terminal 60 amino acid repeat, the transmembrane region and cytoplasmic exons are used in the same order in all Crry transcripts. This suggests that the Crry gene product is not found as a secreted protein, but only as a cell surface bound protein. DNA sequence analysis of the Crry-ps gene indicates that this sequence most likely represents a pseudogene resulting from a processed mRNA transcript from the Crry gene. This conclusion is based on the lack of intervening sequences in the Crry-ps gene and the observation that the Crry-ps gene sequence contains both an 11-bp deletion within the "coding" region and a degenerate poly A tail at the 3' end of the homologous sequence. Additionally, RNA protection analysis indicates that mRNA cannot be detected which matches the Crry-ps sequence. PMID- 2307849 TI - Rearrangement of VHa1-encoding Ig gene segment to the a2 chromosome in an a1/a2 heterozygous rabbit. Evidence for trans recombination. AB - VDJ genes were cloned from leukemic B cells of an a1/a2 heterozygous Emu-cmyc transgenic rabbit. Restriction mapping and nucleotide sequence analysis indicated that one clone, 5C3, had a VHa1-encoding gene segment functionally rearranged to a JH gene segment from the a2 chromosome. This VDJ gene may be the result of a trans recombination between a VH gene on the a1 chromosome and a JH gene segment on the a2 chromosome or, it may be the result of a cis recombination if the a2 chromosome contains VHa1-encoding gene segments. PMID- 2307850 TI - RNKP-1, a novel natural killer-associated serine protease gene cloned from RNK-16 cytotoxic lymphocytes. AB - From an RNK-16 lambda-gt11 library, we have isolated and sequenced a novel cDNA rat NK cell protease 1 (RNKP-1) that has characteristics unique to serine proteases. The cDNA clone is 1102 bp and contains a complete open reading frame with an AUG start codon and a TAA stop codon. The open reading frame translates into a protein of 248 amino acids that has one glycosylation site. The characteristic N-terminal Ile-Ile-Gly-Gly and the His, Asp, and Ser amino acid residues that form the catalytic triad of serine proteases are present. The nucleotide and amino acid sequences have 87 and 80% identity, respectively, with the murine CTL-specific serine protease CCPI. However, there are extensive differences in the substrate binding regions of these proteases. Comparison of hydropathic profiles and amino acid sequences of other proteases indicate that RNKP-1 is distinct and belongs to the subfamily of serine proteases of bone marrow origin. Northern blot analysis of poly A+ RNA from rat splenocytes cultured with Con A showed 1000 and 1400 nucleotide mRNA are detected with RNKP-1 after 1 day of Con A-stimulation. The expression of the two mRNA bands continues through day 5 of culture with the lectin and may represent RNKP-1 mRNA plus related sequences due to cross-hybridization. RNKP-1 is also expressed in RNK-16 cells, but is not expressed in freshly isolated rat splenocytes, brain, lung, or lymph node tissues. The induction of RNKP-1 expression in the Con A-cultured spleen cells is accompanied by increases in both NK and lymphokine-activated killer lymphocyte activities. These data indicate that RNKP-1 is a unique serine protease that may be preferentially expressed in NK cells. PMID- 2307851 TI - Measurement of nonradioactive isotopes of copper in hair with inductively coupled plasma mass spectrometry. AB - A method is reported for tracing dietary enriched (99.61 atom %) nonradioactive 65Cu in rat hair. The method is based on the measurement of the two nonradioactive isotopes of copper (i.e., 63Cu and 65Cu) in rat hair by using inductively coupled plasma mass spectrometry (ICP-MS). Sodium, known to cause interferences in ICP-MS analyses, was removed by using an ion-exchange procedure. Correlation between the diet and hair element concentration levels have been reported. Controversy in the literature exists about the validity of elemental analyses of hair because elements may be incorporated in hair from the diet and body stores during growth, as well as from environmental sources. Tracing dietary elements in hair during growth would eliminate the uncertainness of this procedure. In nature, copper exists as 69.174 atom % 63Cu and 30.826 atom % 65Cu expressed as the 63Cu/65Cu ratio of 2.2400. Enriched (99.61 atom %) 65Cu was obtained and used to label the dietary source of copper. Data showed that 50% of the copper in the rat hair of rats gavaged with the enriched 65Cu isotope was due to 65Cu and 50% was natural isotope-abundant copper. PMID- 2307852 TI - Detection of pemphigus vulgaris and pemphigus foliaceus antigens by immunoblot analysis using different antigen sources. AB - In an immunoblot analysis with human epidermal extract as a source of antigens, all (28/28) pemphigus vulgaris (Pv) sera showed a specific reactivity with a 130 kD protein. Several, but not all, Pv sera reacted with similar antigens in both a bovine muzzle desmosome preparation and extract of cultured human squamous carcinoma cells. On the other hand, some pemphigus foliaceus (Pf) sera exhibited reactivity with a 150-kD protein, which is most likely desmoglein I, in both the human epidermal extract and the bovine desmosome preparation, but no Pf serum reacted with this antigen in the squamous carcinoma cell extract. Furthermore, 4/16 Pv sera also reacted with a 150-kD protein in the desmosome preparation, which seemed to be the same as Pf antigen. These results show a relationship between antigens of both Pf and Pv and desmosomes, as well as heterogeneities of both Pv and Pf antigens in terms of antigenic molecules or epitopes. Furthermore, this study presents the possibility that immunoblot analysis can be routinely used for differentiation of Pv and Pf antibodies. PMID- 2307853 TI - An optimized freeze-fracture replication procedure for human skin. AB - This in vitro study aimed at substantial modification of the freeze-fracture replication technique (FFRT) which should result in an optimal visualization of the ultrastructure of human skin. The technique was modified in two ways: firstly, the conventional sample holders such as gold cups and copper plates were replaced by silver cylinders (83.5% silver, 16.5% copper) resulting in almost perpendicular cross fractures through the skin. Secondly, the replica cleaning procedure was optimized through the following sequence of treatments. Firstly, a mild tissue destruction was obtained by simultaneous lipid solvation and water extraction with absolute methanol (20 h), followed by protein denaturation with dimethyl sulfoxide (DMSO, 24 h). Subsequently, a final treatment was given using an alkaline sodium hypochlorite solution (20% KOH/13% NaClO; 1:3 v/v, 4 d). After rinsing the replicas for 45 min in aqua bidest, they were mounted on copper grids and examined in the transmission electron microscope (TEM). The combination of the unorthodox fracturing method and the optimized cleaning procedure yielded large, practically undamaged and very clean replicas of near perpendicular cross fractures through human skin. Common handicaps related to current freeze-fracture procedures when applied to skin, such as incomplete cleaning and fragmentation of replicas and oblique or irregular fracturing planes, can largely be avoided in this way. In this paper a complete description of the method is given, and a number of advantages are illustrated with the aid of TEM micrographs. PMID- 2307854 TI - Properties of transdermal histamine iontophoresis: differential effects of season, gender, and body region. AB - Histamine iontophoresis is demonstrated to be a reliable model for the study of inflammatory skin responses. It has the advantage of a non-invasive and uniform mode of application and is free of unwanted side effects. The wheal and flare responses to histamine are linearly related to dose over a wide range of stimulus strengths (r = 0.88). In summer, wheal responses were smaller, probably due to increased thickness of the epidermis. Female subjects generally expressed larger wheal responses than males, presumably due to differences in epidermal thickness and structure. There were significant regional differences in wheal, flare, and laser Doppler recorded flux responses. Ratings of itch sensations also showed clear, but less pronounced, differences of body regions. Significant regional differences of wheal and flare responses existed. Sensory discrimination of different stimulus levels was demonstrated with visual analogue scale ratings. PMID- 2307855 TI - Evaluation of transforming growth factor beta and type I procollagen gene expression in fibrotic skin diseases by in situ hybridization. AB - Full thickness biopsies of affected skin and fascia from one patient with diffuse fasciitis and eosinophilia (DF), two patients with generalized morphea (GM), and five patients with progressive systemic sclerosis (PSS) of recent onset were examined for the expression of transforming growth factor beta 1 (TGF beta 1) and type I procollagen genes by in situ hybridization with human sequence-specific cDNA. An increased number of fibroblasts showing clearly detectable expression of pro alpha 1(I)collagen gene was found in all fibrotic lesions when compared with unaffected skin from the patient with DF and skin from two normal individuals examined in parallel. Expression of the TGF beta 1 gene was noted in a fibroblast subpopulation of the affected tissues from the patients with DF and GM. In contrast, the TGF beta 1 gene was not expressed at a detectable level in affected skin from the five patients with PSS. The results suggest that TGF beta 1 may play a role in the development of skin fibrosis in cases of DF and GM. However, from these studies, we cannot implicate TGF beta 1 in the pathogenesis of skin fibrosis in PSS. PMID- 2307856 TI - Water permeation of reaggregated stratum corneum with model lipids. AB - Corneocytes were prepared from stratum corneum after extraction of the lipids and then were reaggregated with model lipids to form a membrane. The transport of water through the membrane was found to be similar to earlier published values for reaggregated stratum corneum formed with the indigenous lipids. Similar values were also obtained when only partially saponified free fatty acids were present as lipids. These results support an earlier hypothesis, that the lipid barrier to water penetration of the stratum corneum is determined by the structural organization of the lipids, not by the exact chemical structure of individual species. PMID- 2307857 TI - Establishment of a human cutaneous T-cell lymphoma in C.B-17 SCID mice. AB - Investigation into the immunobiology of cutaneous T-cell lymphomas (CTCL) would be facilitated by the development of a suitable experimental system. The recent use of mice with severe combined immune deficiency (SCID) as a vehicle to study the human immune system prompted us to try to establish CTCL in SCID mice. We found that a CD4+ lymphocytic infiltrate characteristic of CTCL was maintained within patient skin grafts in place on natural killer cell depleted SCID mice for the month of observation. CTCL cells were not found outside the human skin graft. This chimeric model using SCID mice and patient lesional skin should provide a useful tool to characterize CTCL/skin microenvironmental interactions and to test new therapeutic approaches. PMID- 2307858 TI - Constitutive expression of Ia molecules by murine epithelial cells: a comparison between keratinocytes and enterocytes. PMID- 2307860 TI - Abstracts of the 1989 annual meeting of the Societe Francophone de Recherche Dermatologique. Reims, France, September 19 and 20, 1989. PMID- 2307859 TI - Antigen-presenting cells in the induction of contact hypersensitivity in mice: evidence that Langerhans cells are sufficient but not required. PMID- 2307861 TI - [42d meeting of the Japan Society of Obstetrics and Gynecology. 14-17 April 1990, Tokyo. Abstracts]. PMID- 2307863 TI - English abstracts of proceedings of the twenty-seventh congress of the Japan Society for Cancer Therapy. Nagoya, Oct. 25, 26, 27, 1989. PMID- 2307862 TI - [Proceedings of the 63d meeting of the Japanese Orthopaedic Association. Nagoya, 13-15 April 1990. Abstracts]. PMID- 2307864 TI - Carpal tunnel syndrome in association with vibration white finger. AB - In a prospective study, eight patients with 15 hands affected by both vibration white finger and carpal tunnel syndrome were treated by surgical decompression of the carpal tunnel. On review six months later, the symptoms of carpal tunnel syndrome were improved in all cases and the symptoms of white finger were improved in half of the cases. Nerve conduction studies and palmar skin histology are discussed. PMID- 2307865 TI - Perineural tumour spread: an unusual cause of carpal tunnel syndrome. AB - We describe the development of the carpal tunnel syndrome in a 58-year-old man, from perineural spread of a previously-excised cutaneous malignancy. PMID- 2307866 TI - Predictive factors in the non-surgical treatment of carpal tunnel syndrome. AB - To identify which patients are likely to respond the medical management of carpal tunnel syndrome, 331 hands in 229 patients were evaluated. They were then treated with a wrist splint and anti-inflammatory medication. Follow-up averaged 15.4 months (minimum six months). Treatment was successful in 18.4%. Statistical evaluation identified five factors which were important in predicting response to treatment: age over 50 years, duration over ten months, constant paraesthesiae, stenosing flexor tenosynovitis, and a Phalen's test positive in less than 30 seconds. When none of these factors was present, two-thirds of patients were cured by medical therapy. 59.6% of patients with one factor, 83.3% with two factors, and 93.2% with three factors failed. No patient with four or five factors present was cured by medical management. PMID- 2307867 TI - Use of a flap of flexor retinaculum to cover bone after osteophyte removal within the carpal tunnel. AB - We describe three instances of ruptured flexor pollicis longus tendons due to bony spurs within the carpal tunnel. In each case, the bony spur was excised and the remaining exposed bone was covered with a flap of flexor retinaculum. PMID- 2307868 TI - Incidence of post-traumatic arthrosis after primary healing of scaphoid fractures: a clinical and radiological study. AB - In a retrospective study of 229 patients with healed fractures of the waist of the scaphoid, the incidence and development of post-traumatic radiocarpal arthrosis was studied. With a minimum follow-up period of seven years, 5.2% of patients showed radiological evidence of radiocarpal arthrosis. It is concluded that an alteration of the carpal dynamics, due to deformation and shortening of the scaphoid, is the most likely cause of post-traumatic arthrosis after primary healing of scaphoid fractures. PMID- 2307869 TI - Foreign body in the median nerve: a complication of acupuncture. AB - Fracture of an acupuncture needle resulted in a foreign body within the carpal tunnel of a patient who then developed median neuropathy. The needle fragment was recovered from within the median nerve during carpal tunnel release, with rapid post-operative relief of symptoms. Development of peripheral neuropathy is a potential complication of acupuncture. PMID- 2307870 TI - Mucous cyst of the distal interphalangeal joint: treatment by simple excision or excision and rotation flap. AB - Thirty-five patients who had thirty-seven mucous cysts excised from the distal interphalangeal joints were reviewed not less than one year later. Seven out of 25 which had been treated by simple excision recurred, whereas only one out of twelve treated by excision and skin closure with a rotation flap recurred. PMID- 2307871 TI - Sequential forearm intravenous regional and infiltration anaesthesia: value for haemostasis. AB - Intravenous regional anaesthesia using 0.5% lignocaine with a forearm tourniquet is a satisfactory technique for operations on the distal forearm, wrist and hand. Since recovery of pain sensation is rapid, haemostasis after release of tourniquet becomes difficult and sometimes impossible. Local wound infiltration or metacarpal block with 1% lignocaine just before release of the tourniquet can allow subsequent haemostasis and wound closure to be carried out without causing pain. 55 patients received this sequential forearm intravenous regional and infiltrative anaesthesia. Subsequent haemostasis and wound closure could be carried out without pain in 51 patients (92.7%); three patients (5.5%) noticed mild discomfort but the operations could be finished without any additional anaesthetic agent. No complications were encountered with this modified technique. PMID- 2307872 TI - Acute ischaemia of the hand following accidental radial artery infusion of Depo Medrone. AB - Acute ischaemia of the hand following the accidental intra-arterial injection of steroid has not, to our knowledge, been previously reported. We present such a case of the injection of Depo-Medrone with Lidocaine (Upjohn) into the right radial artery during attempted treatment of stenosing tenosynovitis of the right thumb. The resultant acute ischaemia was successfully managed after 20 hours by a combination of surgical thrombectomy, intra-arterial streptokinase and intravenous heparin and thymoxamine. PMID- 2307873 TI - Non-union of Colles' fracture: report of two cases. AB - There are few reports in the literature concerning non-union of Colles' fractures or its treatment. We describe two cases in which the fractures had been treated in the standard manner by reduction and plaster immobilisation for six weeks. The wrists of both patients were mobilised free of external support for several months before the complication of non-union was diagnosed. A simple radiographic technique for the diagnosis of non-union is described, using flexion and extension views of the wrist, and a method of treatment is outlined. PMID- 2307875 TI - Complete detachment of the epiphysis of the distal phalanx. AB - A case of fracture-separation of the distal phalanx epiphysis, with complete detachment from soft tissue, is reported and discussed. PMID- 2307874 TI - Rotational deformity following metacarpal fracture. AB - Ninety-one consecutive patients with 98 metacarpal fractures were looked at prospectively for rotational deformity. Whilst a quarter had minor rotation of the fracture of less than 10 degrees, only five had more than this. In just two cases, was there rotational instability requiring operative intervention. Assessment of rotational deformity must include an end-on view of the finger nail, as there is often restricted movement at the metacarpal phalangeal joint following fracture. PMID- 2307876 TI - Deep palmo-plantar wart causing extensive bone erosion: brief report. AB - A case is described in which a deep palmo-planar wart (myrmecia) caused erosion of the underlying phalanx. PMID- 2307877 TI - The validation of measures of outcome following suture of divided peripheral nerves supplying the hand. AB - Erik Moberg pioneered the idea of validating measures of sensory function following peripheral nerve suture by correlating their results with those of functional tests. However it is important that powerful prior variables (age at suture, time elapsed since suture and delay between injury and suture) be controlled. Failure to do this may result in spurious correlations, as illustrated by analysis of two sets of data, one collected by the author and the other given in the classic paper of Onne (1962). PMID- 2307878 TI - Liquid silicone as a lunate prosthesis. AB - Eleven patients with lunatomalacia were treated by excision of the lunate and instillation of liquid silicone. The silicone vulcanised and formed an in-situ molded prosthesis. The patients were reexamined after a mean of 7.1 years. Four patients were pain-free and two had pain only at work; three had not been improved by the operation and two had undergone arthrodesis. The patients with good results all belonged to group IV pre-operatively. Surprisingly, no patient showed any sign of silicone synovitis, although all the prostheses except one had either fractured or deformed. The reasons for this are discussed and the indications for the operation established. PMID- 2307879 TI - Radial shortening for Kienbock's disease: factors affecting the operative result. AB - The operative results of radial shortening in 23 patients with Kienbock's disease were analysed on the basis of age, stage of disease, ulnar variance and the amount of radial shortening. The patient's age was found to be the factor which affected the operative result most and unsatisfactory results were obtained in patients over 30 years old. However, neither the clinical stage nor ulnar variance affected the results significantly and the results in patients with ulnar zero or plus were no worse than in patients with ulnar minus. The risk of ulnar wrist pain was increased when the radius was shortened more than 4 mm in patients with positive or zero ulnar variance. This was an important cause of unsatisfactory operative results. PMID- 2307880 TI - Excessive radial shortening in Kienbock's disease. AB - Two patients with Kienbock's disease who had been treated by radial shortening developed ulnar wrist pain post-operatively due to excessive radial shortening. In both cases, ulnar shortening was required to improve symptoms and function. Excessive radial shortening can cause ulnar wrist pain and compromise the improvement of grip strength and range of motion of the wrist. PMID- 2307881 TI - Clinical and microangiographic studies on rupture of the E.P.L. tendon after distal radial fractures. AB - The authors have treated 14 cases of spontaneous rupture of extensor pollicis longus tendon after fractures of the distal end of the radius, most of which were undisplaced or only slightly displaced. A microvascular study on five cadavers revealed that this tendon is subject to mechanical bending and attrition, has no mesotenon and has a poorly vascularised portion about 5 mm in length, which may be a cause of spontaneous rupture of the tendon. PMID- 2307882 TI - Bennett's fracture. AB - The relationship between the quality of reduction and the occurrence of arthritic changes, symptoms and disability was studied in 41 Bennett's fractures. Excellent position was obtained in five of nine fractures treated by closed reduction and plaster immobilisation, in four of six fractures treated by percutaneous K wire fixation and in 18 of 26 fractures treated by open reduction. After a median interval of 7.3 years, 15 of 18 reviewed patients with fractures healed in excellent position were free of symptoms, but this was so in only six of 13 fractures with residual displacement. The remainder had intermittent slight pain. Radiographic signs of arthritis was found in ten of 24 patients: three of 14 patients with excellent reduction and seven of ten patients with residual displacement. PMID- 2307883 TI - Neurovascular island flap by the disconnecting-reconnecting technique. AB - The authors report nine cases of hetero-digital neurovascular island flaps raised by the "disconnecting-reconnecting" technique for defects of the tactile pad of the thumb. At an average follow-up of 25 months, all cases had good restoration of sensibility without any "double sensibility" phenomenon and patients regained good dexterity. No tender neuromata developed and donor site complications were not troublesome. PMID- 2307884 TI - Interphalangeal dislocations of the fingers treated by an elastic double-finger bandage. AB - A prospective trial of dislocations of the interphalangeal joints of fingers treated by elastic double-finger bandage showed good final results with an almost normal range of motion. The method is found pleasant by the patient, being hygienic and causing no kind of skin reaction. PMID- 2307885 TI - The dorsal plate of the proximal interphalangeal joint. AB - There exists on the articular surface of the central slip of the extensor tendon slip overlying the P.I.P. joint a constant structure which is morphologically similar to the patella of the knee joint and histologically similar to the fibro cartilaginous palmar plate of the P.I.P. joint. It has been termed the dorsal plate. A study of 70 fingers, including 30 examined under magnification and 20 examined histologically, confirmed its constant presence and structure. Its functions appear to include stabilisation of the central extensor tendon and participation in stabilisation of the proximal interphalangeal joint. PMID- 2307886 TI - Extensor tendon repair: an animal model which allows immediate post-operative mobilisation. AB - In adult rabbits, an experimentally transected digital extensor tendon was repaired. The technique employed a tongue, created from the proximal tendon, folded over to bridge the transection and reattached distally. Animals were allowed immediate post-operative mobilisation. Tendon material, 14-120 days post operatively, was examined ultrastructurally in control and experimental animals from four different zones within the repaired tendon. The operation was well tolerated and adhesion free. Associated with the repair, two types of collagen fibril populations were observed. Firstly, in areas where tendon tissue had been removed, there was a population of fibrils with a narrow range of diameters. Secondly, in areas where tendon tissue was subjected to an increased level of stress per unit cross-sectional area, a population of fibrils with a range of diameters similar to that of controls but with a marked increase in the percentage of small diameter fibrils. The relevance of these observations to human tendon repair is discussed. PMID- 2307887 TI - The hand in psoriasis. AB - Fifty-six patients with psoriatic arthropathy have been reviewed to asses the extent and severity of their hand involvement. The hand was affected in 84% of cases. Although the distal interphalangeal joints are said to be classically affected, we found the proximal interphalangeal and metacarpophalangeal to be more frequently involved. Many other findings often associated with rheumatoid arthritis (e.g. boutonniere and swan-neck deformities, or tenosynovitis) can be seen in psoriatic arthropathy. PMID- 2307888 TI - The Chinese forearm flap in reconstruction of the hand. AB - A Chinese flap, based on the radial artery, has been used in 29 patients who presented with problems of reconstruction in the hand. The merits and complications of this procedure are discussed. PMID- 2307889 TI - Location of impaired sensory conduction of the median nerve in carpal tunnel syndrome. AB - Sensory conduction of the median nerve at the carpal tunnel for eight consecutive 1 cm segments of the nerve was evaluated in 217 hands of 153 of our patients with carpal tunnel syndrome. Impairment was found to be highly focal and often confined to a single 1 cm segment of the nerve. The section of the nerve at or just distal to the distal margin of the carpal tunnel was affected most frequently, the section within the tunnel was affected less often, and the section proximal to the tunnel at the level of the mid-carpal and radio-carpal joints was affected least. The greatest contrast between frequencies of slowing at adjacent segments occurred at the proximal and distal margins of the carpal tunnel. The distribution of the nerve impairment was similar between the sexes; however, among the men the segment affected most frequently was located 1 cm distal to the segment affected most frequently among the women. The general pattern of slowing which we found does not substantiate some commonly-held opinions about the aetiology of carpal tunnel syndrome. PMID- 2307890 TI - Carpal tunnel syndrome in pregnancy and lactation. AB - A retrospective study of 40 women with carpal tunnel syndrome developing in pregnancy and 18 women with carpal tunnel syndrome in the puerperium was undertaken. All the cases that developed in pregnancy occurred in the third trimester and resolved within two weeks of delivery. Those cases developing in the puerperium affected women who had breast-fed their infants and their symptoms lasted a mean of 5.8 months. These patients were older and more likely to be primiparous than if the condition occurred in pregnancy. All the pregnant women and none of the lactating women had symptoms of peripheral oedema. Spontaneous resolution with a good response to conservative measures occurred in both groups; only three cases were treated surgically. Residual clinical evidence of median nerve damage was present in 40% of all cases. Carpal tunnel syndrome which develops in pregnancy appears to be a separate clinical entity to that developing in the puerperium. PMID- 2307891 TI - Carpal tunnel syndrome in black South Africans. AB - The incidence and the aetiology of chronic carpal tunnel syndrome in black South Africans was evaluated. This study showed that the incidence of idiopathic carpal tunnel syndrome was very low in this population group and that most patients who presented with symptoms and signs of chronic carpal tunnel syndrome had a specific pathology. A rare case of tumoral calcinosis causing carpal tunnel syndrome is presented. A case of perineural lipofibroma causing carpal tunnel syndrome is also described. PMID- 2307892 TI - Heerfordt syndrome: a cause of facial paralysis. AB - Heerfordt syndrome is an unusual manifestation of systemic sarcoidosis and is characterized by parotitis, uveitis, and facial nerve paralysis. A case is presented and the clinical manifestations are discussed. Angiotensin converting enzyme assays along with tissue biopsy demonstrating noncaseating granulomas confirm the diagnosis. PMID- 2307893 TI - Pennington Biomedical Research Center. Philanthropy refocuses nutrition thinking. AB - Pennington Biomedical Research Center (PBRC) is a $26 million facility constructed as the initial component of a generous gift from Baton Rouge oilman and philanthropist Claude B. "Doc" Pennington. The US Department of Agriculture provided a $9.4 million grant for equipment for the center. The Louisiana Public Facilities Authority provided $4.1 million for initial operating capital, and the center received a $3.5 million grant from the US Army for military nutrition research. The Pennington Center Foundation, a non-profit support organization, has so far raised $4.6 million from individuals, corporations, and private foundations. Traditional academic funding sources such as the National Institute of Health are also providing funding for research. PMID- 2307894 TI - Louisiana the sportsman's paradise: fishing lure of the esophagus. AB - Foreign bodies in the esophagus, such as coins, meat, marbles, buttons, and chicken bones, are quite commonly encountered. We present the case of a fishing lure that was retrieved from the esophagus of a child. Since Louisiana is the "Sportsman's Paradise," it seemed appropriate to report this case in the Journal of the Louisiana State Medical Society. PMID- 2307895 TI - Leukopenia secondary to mycobacterium leprae. AB - Hansen's disease (HD) is one of the major infectious diseases in the world with an estimated total of 12 million cases. Physicians in North America, however, rarely see HD or its manifestations. Hematological manifestations of HD have been reported but are not well appreciated. We report a patient with leukopenia while under treatment for active HD who demonstrated mycobacterial involvement of the bone marrow. PMID- 2307896 TI - The delayed diagnosis of invasive carcinoma of the uterine cervix. AB - While an effective method of screening for uterine cervical cancer is available, utilization of that method has been less than satisfactory in the high-risk indigent population of Louisiana. From 1984 through 1987, 171 new cases of invasive squamous cell carcinoma and 149 new cases of squamous carcinoma in situ of the uterine cervix were examined and/or treated at the Charity Hospital of Louisiana in New Orleans. In the 1984 group, 23 patients of the invasive and no patients of the in situ group died, giving a 5-year survival of 43% and 100% respectively. During the 4 years in question, 84 (49%) patients in the invasive group and 2 (1.3%) in the in situ group had no record of having had a previous cervical cytologic examination. Participation by nongynecology staff physicians, nurses, and nurse's aides in the charity hospitals and clinics in New Orleans and throughout the state could possibly remedy this problem. PMID- 2307898 TI - Prioritizing health care. PMID- 2307899 TI - Economic impact of motor vehicle restraints in Kentucky: a trauma center's experience. AB - Motor vehicle seat belts save lives and decrease the cost of care. Victims involved in motor vehicular accidents requiring ED evaluation and in-patient care were evaluated for seat belt usage. In addition to outcome parameters, the economic impact was assessed. During the five month study period, 38 (14%) restrained drivers and 238 (86%) unrestrained drivers were entered. Unrestrained drivers were more likely to be killed or disabled. The average cost of medical care for unrestrained drivers ($18,165) was significantly higher than that for restrained drivers ($7,634) (p less than .02). Twenty-eight percent of the unrestrained drivers' bills were paid with public funds. Assuming mandatory seat belt legislation would alter usage patterns as demonstrated in other states, the Commonwealth of Kentucky could save not only lives but millions of tax dollars. PMID- 2307897 TI - ECG of the month. Hand-made. Pseudoarrhythmia. PMID- 2307900 TI - Surgical repair of atypical coarctation of the abdominal aorta in an infant. AB - A seven-week-old infant with multiple areas of coarctation of the abdominal aorta and renal artery pathology underwent staged surgical repair of his malformations in our medical center. The clinical and routine echocardiographic evaluations suggested the diagnosis of atypical coarctation of the aorta. The exact anatomical characteristics of his vascular malformations were established by repeated angiocardiographic studies, which should be performed in any patient in which the diagnosis of atypical coarctation of the aorta is suspected. PMID- 2307901 TI - Hot tub (Pseudomonas) folliculitis. AB - Folliculitis caused by Pseudomonas aeruginosa is a rare, adverse effect of the therapeutic or recreational use of hot tubs, whirlpools, and occasionally swimming pools. The condition is characterized by painful, papulopustular skin lesions often accompanied by low-grade fever, malaise, and other systemic symptoms. Prompt recognition and treatment may shorten the duration of the disease and, more importantly, prevent further cases by identifying the source of exposure. PMID- 2307902 TI - Kentucky Medical Association assumes role to protect youth from tobacco. PMID- 2307903 TI - Needle localization and biopsy of mammographic abnormalities. PMID- 2307904 TI - Back to the future. PMID- 2307905 TI - Kupffer cell proliferation and glucan-induced granuloma formation in mice depleted of blood monocytes by strontium-89. AB - In mice with prolonged severe monocytopenia induced by selective irradiation of the bone marrow with the bone-seeking isotope 89Sr, the proliferative capacity of Kupffer cells was studied by immunohistochemistry with an anti-mouse macrophage monoclonal antibody, F4/80, ultrastructural peroxidase (PO) cytochemistry, and tritiated thymidine (3HTdR) autoradiography. The number and 3HTdR uptake of Kupffer cells were significantly increased in the splenectomized mice after severe monocytopenia had continued for more than 4 wk, and almost all the Kupffer cells showed a localization pattern of PO activity similar to that of resident macrophages in the liver of normal mice. In the glucan-induced granuloma formation in similar monocytopenic mice, Kupffer cells proliferated, conglomerated, and transformed into epithelioid cells, which fused together to become multinuclear giant cells. These results suggest that Kupffer cells are a self-renewing population by their own cell division and can participate actively in granulomatous inflammations in severely monocytopenic and intact mice. PMID- 2307906 TI - Cooperation between platelets and neutrophils for paf-acether (platelet activating factor) formation. AB - Association of platelets and neutrophils is frequently observed within thrombi or inflammatory sites. Interactions between these two cell populations have been reported for the production of several mediators of inflammation such as hydrogen peroxides or leukotrienes. Another potential mediator of thrombosis and inflammation is paf-acether, which is synthesized by activated platelets and neutrophils. Since platelets form and release large amounts of the paf-acether precursor lyso paf-acether, platelet and neutrophil cooperation for paf-acether biosynthesis was investigated. Purified human neutrophils (4 x 10(6)/ml) stimulated by opsonized zymosan (ZC, 1 mg/ml) formed 4.5 +/- 2.5 ng/ml paf acether. Human washed platelets (3 x 10(8)/ml) stimulated with thrombin (1 IU/ml) formed 0.60 +/- 0.43 ng/ml paf-acether. Platelets and neutrophils, incubated together and both stimulated by their specific agonist, formed more than twice as much paf-acether as did platelets and neutrophils separately (10.90 +/- 4.25 ng/ml, n = 6, P less than .001). The formation of lyso paf-acether and the release of lysozyme and LDH were unchanged under the cooperation conditions. The formation of paf-acether almost doubled (10.24 +/- 3.81 ng/ml paf-acether vs. 5.30 +/- 2.23, P less than .05, n = 4) when ZC-stimulated neutrophils were incubated with supernatants from thrombin-stimulated platelets as well as with synthetic lyso paf-acether. Extracted and purified lyso paf-acether from thrombin stimulated platelets led to an increase of biosynthesis of paf-acether by neutrophils (13.86 +/- 2.26 ng/ml paf-acether vs. 5.76 +/- 0.38, P less than .05, n = 3). These results indicate that a cooperation between platelets and neutrophils exists for paf-acether formation. The phenomenon depends on a platelet-derived soluble factor, possibly lyso paf-acether. This cell-to-cell interaction is of interest since paf-acether is formed by and acting on platelets and neutrophils and represents a molecular basis for potent amplification of inflammatory reactions. PMID- 2307908 TI - Dispersion population models discrete in time and continuous in space. AB - We analyze a discrete-time model of populations that grow and disperse in separate phases. The growth phase is a nonlinear process that allows for the effects of local crowding. The dispersion phase is a linear process that distributes the population throughout its spatial habitat. Our study quantifies the issues of survival and extinction, the existence and stability of nontrivial steady states, and the comparison of various dispersion strategies. Our results show that all of these issues are tied to the global nature of various model parameters. The extreme strategies of staying-in-place and going-everywhere uniformly are compared numerically to diffusion strategies in various contexts. We approach the mathematical analysis of our model from a functional analysis and an operator theory point of view. We use recent results from the theory of positive operators in Banach lattices. PMID- 2307907 TI - Simultaneous flow cytometric measurements of cytoplasmic Ca++ and membrane potential changes upon FMLP exposure as HL-60 cells mature into granulocytes: using [Ca++]in as an indicator of granulocyte maturity. AB - Treatment of human leukemic HL-60 cells with N,N-dimethylformamide (DMF) induces them to mature until they reach granulocytoid morphology 3-6 d later. We have reported a maturation-dependent ability of these cells to respond to phorbol myristate acetate (PMA), as evaluated by membrane depolarization and by oxidative burst product formation (Newburger et al.: J. Biol. Chem. 259,3771, 1984). More recently we have attempted to develop techniques for simultaneous evaluation of these parameters during HL-60 cell maturation. Here, we compare the cytoplasmic [Ca++] and membrane potential changes elicited by the chemotactic peptide fMLP via simultaneous measurement of individual cells in a fluorescence-activated cell sorter (FACS), as done previously for mature granulocytes (Lazzari et al.: J. Biol. Chem. 261,9710, 1986). The stimulus-induced [Ca++]in changes are detected with the fluorescent probe Indo-1 and reproducibly increase in magnitude for a subpopulation of cells as the cells mature into granulocytes. Ca++ responsiveness to formyl peptide is restricted to a subpopulation of HL-60 granulocytes which expresses receptors for chemotactic peptide and consistently increases in magnitude (in response to the same concentration of agonist) with maturation. In contrast, there is less consistency in the direction or magnitude of membrane potential changes elicited under the same circumstances from the same maturing HL 60 cells. PMID- 2307909 TI - The storage and recall of auditory memory. AB - The architecture of the auditory memory is investigated. The auditory information is assumed to be represented by f-t patterns. With the help of a psycho-physical experiment it is demonstrated that the storage of these patterns is highly folded in the sense that a long signal is broken into many short stretches before being stored in the memory. Recognition takes place by correlating newly heard input in the short term memory to information previously stored in the long term memory. We show that this correlation is performed after the input is accumulated and held statically in the short term memory. PMID- 2307910 TI - Inconsistencies in standard approximations for selection coefficients at loci affecting a polygenic character. AB - Inconsistencies exist in the standard expansions used to approximate selection coefficients for alleles at a locus underlying a quantitative character. Allelic (marginal) fitnesses obtained from expansions based on average excesses differ from allelic fitnesses obtained from expansions based on genotypic values. Similarly, W, the mean population fitness based on summing over either allelic or genotypic fitnesses usually differs mean population fitness obtained by averaging over the unrestricted phenotypic distribution. A consistent value of W requires no variation in genotypic values. If, as suggested by Nagylaki (1984), expansions are corrected for the decrease in phenotypic variance resulting from conditioning on the presence of a particular allele or genotype, inconsistencies still exist. Unless integral of W(z)[Vzp"(z) + zp'(z) + p(z)] dz = 0, where p(z) is the phenotypic probability density function, Vz the phenotypic variance, W(z) the fitness of phenotypic value z, the primes denote differentiation with respect to z, allelic fitnesses based on average effects differ from allelic fitnesses based on genotypic values. This condition must also be satisfied in order for either expansion to give a consistent W, as first shown by Nagylaki. For arbitrary W(z), this is satisfied if and only if phenotypes are normally distributed. PMID- 2307911 TI - A deterministic approach to survival statistics. AB - Survival functions of the form p(t) = exp[-(lambda t) gamma], gamma greater than 0 can be generated by deterministic nonlinear, asymptotically stable (chaotic) dynamical systems. These systems thus provide an alternative to stochastic interpretations of failure time data. We use this approach to analyze cancer patient survival statistics. In this manner we are able to obtain fresh insights into the implications of negative and positive clinical trials. PMID- 2307912 TI - Modelling human power and endurance. AB - A generalised three component hydraulic model has been proposed to represent the human bioenergetic processes relating internal energy stores to performance during exercise, and into recovery. Further development of the model allows testable predictions to be made. In particular in this paper I examine certain hypotheses of chemical fuel shortage as a subgroup of the potential causes of fatigue, and their implications for maximal power and for endurance. The assumption that the limitation to sustainable power is direct proportionality to the glycogen store remaining, appears the most feasible. Based on this assumption, equations for the decline in maximum attainable power over time, the endurance at fixed workrates and the endurance at incremental tests (as a function of the increment slope) are obtained. Using published data for fit males, the maximum exertable power declines after about 6 s at 972 W to very low levels after about 2 min. For constant powers selected between 208 and 927 W, endurance declines from ad infinitum to only 6 s. Endurance at VO2max is predicted to be about 9 min. For incremental exercise tests of slope ranging from 30 W/min to 60 W/min, endurance lessens from 14 to 9 min. In these tests the anaerobic threshold is reached in times between 6 and 3 min. Although the power at termination of a test increases with incremental slope, terminal oxygen consumption is effectively constant. Almost all these model predictions are observed to correspond well with published experimental findings. These results suggest that the model can be used to represent an adequate overview of the operation of the human bioenergetic system. PMID- 2307913 TI - Population models for diseases with no recovery. AB - An S----I epidemic model with a general shape of density-dependent mortality and incidence rate is studied. The asymptotic behaviour is global convergence to an endemic equilibrium, above a threshold, and to a disease-free equilibrium, below the threshold. The effect of vaccination is then examined. PMID- 2307914 TI - Convergence to spatial-temporal clines in the Fisher equation with time-periodic fitnesses. AB - The asymptotic behavior as t----infinity of the solutions with values in the interval (0, 1) of a reaction-diffusion equation of the form (Formula: see text) is studied. Conditions on m which are satisfied when m is nonincreasing in mu and which imply that every solution converges to some periodic limit function are found. Except in some very special and well-defined circumstances, the limit is the same for all solutions, so that it is a global attractor. This global attractor may be one of the trivial solutions 0 or 1, or it may be a spatial temporal cline. The linear stability properties of the trivial states serve to distinguish between these cases. PMID- 2307915 TI - Stability in chemostat equations with delayed nutrient recycling. AB - The growth of a species feeding on a limiting nutrient supplied at a constant rate is modelled by chemostat-type equations with a general nutrient uptake function and delayed nutrient recycling. Conditions for boundedness of the solutions and the existence of non-negative equilibria are given for the integrodifferential equations with distributed time lags. When the time lags are neglected conditions for the global stability of the positive equilibrium and for the extinction of the species are provided. The positive equilibrium continues to be locally stable when the time lag in recycling is considered and this is proved for a wide class of memory functions. Computer simulations suggest that even in this case the region of stability is very large, but the solutions tend to the equilibrium through oscillations. PMID- 2307916 TI - The patient, the practitioner, and wellness: paradigm lost, paradigm gained. PMID- 2307917 TI - A comparison of patients and patient complaints at six chiropractic teaching clinics. PMID- 2307918 TI - Protection of practice rights. PMID- 2307919 TI - Effects of chiropractic treatment on blood pressure and anxiety: a randomized and controlled trial. PMID- 2307920 TI - Effects of a chiropractic adjustment on changes in pupillary diameter: a model for evaluating somatovisceral response. PMID- 2307921 TI - 'Snapping hip' and sacroiliac sprain: example of a cause-effect relationship. PMID- 2307922 TI - Questions of authorship and financial conflict of interest. PMID- 2307923 TI - The role of experience in clinical accuracy. AB - A randomized controlled trial was performed to study the effect of various teaching techniques on students performing sacroiliac motion palpation tests. This trial assessed the interexaminer reliability of interns in their final year at a chiropractic college, and compared their results prior to and following 1 year of clinical experience. The study also compared the intra- and interexaminer reliability of experienced clinicians. The results were analyzed via the Kappa coefficient. Kappa values for interns ranged from 0.00 to 0.30, with no significant differences noted at the end of 1 year of clinical experience. The interexaminer reliability of experienced clinicians was 0.00 to 0.167, whereas their intraexaminer reliability ranged from 0.15 to 1.00. These results question the role of experience in improving clinical accuracy between examiners performing sacroiliac motion palpation. Results analyzed for intraexaminer agreement were moderate to almost perfect. We conclude that experience does not play a significant role in the diagnostic test analyzed, but rather that clinicians may establish their own criteria by which to determine the standards of a given test. PMID- 2307924 TI - Manual therapy considerations at the thoracolumbar junction: an anatomical and functional perspective. AB - Anatomically, the human thoracolumbar junction demonstrates considerable resistance to rotary motion in an effort to decrease torsional stress through an area of marked functional transition. Despite this, rotational manipulation and mobilization procedures have been advocated in the treatment of painful mechanical disorders originating from the thoracolumbar junction. The rationale behind vigorous manipulative techniques, particularly those incorporating extension, is challenged in light of cadaveric histological studies of this region, as well as both in vivo and experimental biomechanical investigations. Judicious use of traction and mobilization procedures are recommended. PMID- 2307925 TI - Mechanics of six-legged runners. AB - Six-legged pedestrians, cockroaches, use a running gait during locomotion. The gait was defined by measuring ground reaction forces and mechanical energy fluctuations of the center of mass in Blaberus discoidalis (Serville) as they travelled over a miniature force platform. These six-legged animals produce horizontal and vertical ground-reaction patterns of force similar to those found in two-, four- and eight-legged runners. Lateral forces were less than half the vertical force fluctuations. At speeds between 0.08 and 0.66 ms-1, horizontal kinetic and gravitational potential energy changes were in phase. This pattern of energy fluctuation characterizes the bouncing gaits used by other animals that run. Blaberus discoidalis attained a maximum sustainable stride frequency of 13 Hz at 0.35 ms-1, the same speed and frequency predicted for a mammal of the same mass. Despite differences in body form, the mass-specific energy used to move the center of mass a given distance (0.9 J kg-1m-1) was the same for cockroaches, ghost crabs, mammals, and birds. Similarities in force production, stride frequency and mechanical energy production during locomotion suggest that there may be common design constraints in terrestrial locomotion which scale with body mass and are relatively independent of body form, leg number and skeletal type. PMID- 2307926 TI - Interactions of light and gravity reception with magnetic fields in Xenopus laevis. AB - Tadpoles of Xenopus laevis are shown to respond to magnetic fields using a gravity-related test paradigm. They exhibit a directional selectivity with respect to angular variations of the inclination of low-intensity magnetic fields. This response is abolished when the optic nerves of the tadpole are transected, indicating that the peripheral optical system is involved in the detection of magnetic fields. PMID- 2307927 TI - Glucose transport in fish erythrocytes: variable cytochalasin-B-sensitive hexose transport activity in the common eel (Anguilla japonica) and transport deficiency in the paddyfield eel (Monopterus albus) and rainbow trout (Salmo gairdneri). AB - Erythrocytes from individual common eels (Anguilla japonica Temminck and Schlegel) exhibited widely variable initial rates of cytochalasin-B-sensitive 3-O methyl-D-glucose (3-OMG) zero-trans influx, in the range of 0-19.5 mmol l-cells-1 h-1 (5 mmol l-1 extracellular concentration at 20 degrees C, 50 animals tested). Storage of cells at 4 degrees C in a glucose-containing medium for up to 72 h had no effect on 3-OMG uptake, and there was no correlation between the sugar permeabilities of erythrocytes from different fish and intracellular ATP levels. Adrenaline and noradrenaline increased cytochalasin-B-sensitive 3-OMG transport activity; half-maximal stimulation occurred at catecholamine concentrations in the region of 1 mumol l-1. This catecholamine-induced stimulation of sugar transport appeared to be independent of the basal cytochalasin-B-sensitive 3-OMG permeability of the cells. Kinetically, catecholamines increased the Vm of transport without changing the apparent Km (approx. 1.4 mmol l-1). Saturable 3 OMG influx was inhibited by phloretin, D-glucose, D-deoxyglucose and D-galactose, but not by D-fructose and L-glucose. Transporter stereoselectivity was confirmed by direct measurements of D- and L-glucose uptake. Erythrocytes from two other fish species, Monopterus albus Richardson (paddyfield eel) and Salmo gairdneri Richardson (rainbow trout), unlike those from the common eel, were uniformly deficient with respect to cytochalasin-B-sensitive 3-OMG and D-glucose transport activity. Catecholamines had no effect on sugar uptake in these species. PMID- 2307928 TI - Cytoplasmic pH recovery in acid-loaded haemocytes of squid (Sepioteuthis lessoniana). AB - Cytoplasmic pH (pHi) of haemocytes of bigfin reef squid (Sepioteuthis lessoniana Lesson) was determined with the fluorescent probe, 2',7'-biscarboxyethyl-5,6 carboxyfluorescein (BCECF). The pHi of haemocytes suspended in nominally HCO3(-) free medium (extracellular pH 7.4) averaged (+/- S.E.) 7.32 +/- 0.02. Intracellular pH was independent of external Na+ concentration and varied only slightly with changes in extracellular pH (pHe) (delta pHi/delta pHe = 0.16 over the pHe range 6.8-7.8). Addition of weak acids (sodium propionate, potassium acetate) to haemocyte suspensions resulted in a rapid decrease in pHi. Haemocyte pHi then recovered with an average half-time of 3-4 min. Recovery of pHi was independent of external Na+ concentration and insensitive to amiloride, but was abolished by N-ethylmaleimide (NEM). These results argue against the involvement of plasma membrane Na+/H+ exchange or other Na(+)-dependent transport mechanisms in the pHi recovery of acid-loaded haemocytes. The results suggest that there is an NEM-sensitive proton extrusion mechanism in the plasma membrane of squid haemocytes. PMID- 2307929 TI - Structural requirements for pairing of alpha and beta chains in HLA-DR and HLA-DP molecules. AB - To test for the assembly of human MHC class II molecules having an alpha chain from one isotype (HLA-DR, -DQ, or -DP) and the beta chain of another (mixed isotypic pairs), murine fibroblasts were transfected with expressible cDNAs encoding the different class II alpha and beta chains. A rapid and efficient transient transfection system was developed using a polyoma virus-based vector. Typically, 30-50% of cells transfected using this system expressed high levels of class II molecules on their surface, but only with matched isotypic pairs. Biochemical analysis of cells transfected with matched or mixed isotypic pairs of the DR and DP molecules revealed that only matched chains could pair efficiently inside the cell. Thus, the lack of expression of the two mixed isotypic pairs is due to inefficient primary assembly of the class II molecule and not to a processing or transport defect. To define what region of the beta chains controlled their assembly with alpha chains, a series of chimeric cDNA molecules containing both DR and DP beta chain sequences were constructed. Expression of these chimeric beta chains with DR and DP alpha chains was determined by cytofluorimetry and biochemical analysis. Both alpha chains paired with beta chains in which only the beta 1 domain was isotypically matched. In contrast, the pattern of expression of chimeras made at other points within the beta 1 domain was different for DR and DP. These data show that different areas of primary sequence are important for the assembly of different human class II isotypes, and suggest that HLA-DR and -DP molecules have different secondary or tertiary structures in their NH2-terminal domains. PMID- 2307930 TI - Antitumor activity of recombinant interleukin 6 in mice. AB - IL-6 possesses multiple biologic activities that affect a broad range of cells including those directly involved in immune responses as well as cells important in the systemic response to infection or trauma. We now show that purified human rIL-6, when administered alone at relatively high doses that are comparable to therapeutic levels of IL-2, mediated substantial reductions in the number of pulmonary and hepatic micrometastases from four distinct syngeneic tumors. Unlike IL-2, IL-6 injections resulted in neither observable toxicity nor death of the treated mice at the dose regimens used. Host immunosuppression by sublethal total body irradiation before the initiation of therapy prevented the IL-6 antitumor effect, thus suggesting that IL-6 acted through a radiosensitive host component rather than directly on the tumor itself. Moreover, the systemic administration of relatively low doses of IL-6 in combination with subtherapeutic doses of TNF to mice bearing an established weakly immunogenic, syngeneic tumor at a subcutaneous site resulted in marked tumor regression and cure rates. These studies represent the first demonstration of tumor regression mediated by recombinant IL-6 in vivo. PMID- 2307931 TI - In vivo administration of interleukin 2 plus T cell-depleted syngeneic marrow prevents graft-versus-host disease mortality and permits alloengraftment. AB - Previous work from this laboratory has demonstrated that T cell-depleted (TCD) syngeneic marrow can delay, but not prevent, the mortality from acute graft-vs. host disease (GVHD) caused by MHC-mismatched lymphoid cells administered to lethally irradiated mice. We demonstrate here that a protective effect against GVHD is also observed after in vivo treatment with IL-2. Administration of 10,000 50,000 U of IL-2 twice daily for the first 5 d after bone marrow transplantation markedly reduced the mortality from both acute and chronic GVHD induced across complete MHC barriers in lethally irradiated mice, and frequently led to long term survival. Complete allogeneic reconstitution was demonstrated in all long term survivors of this treatment regimen. While either IL-2 or TCD syngeneic marrow administered alone was protective in some experiments, the maximal protective effect was observed after administration of both IL-2 and TCD syngeneic marrow, especially when the effects of IL-2 were suboptimal. The timing of IL-2 administration was critical to this beneficial effect, since a delay of 7 d in commencing IL-2 treatment was associated with accelerated GVHD mortality. This new approach to the prevention of GVHD permits the administration of allogeneic T cells, and may therefore avoid the increased incidence of graft failure and loss of antileukemic effects associated with the T cell depletion of allogeneic marrow, which is otherwise required for the prevention of GVHD. PMID- 2307932 TI - Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes. AB - Essential fatty acid (EFA) deficiency exerts a striking protective effect in several animal models of autoimmune disease. We now report that EFA deprivation prevents diabetes in the BB rat, an animal model of human insulin-dependent diabetes mellitus. In diabetes-prone (DP)-BB rats, the incidences of spontaneous diabetes and insulitis (the pathological substrate of autoimmune diabetes) were greatly reduced by EFA deficiency. This beneficial effect of the deficiency state was also seen in diabetes-resistant (DR)-BB rats that, after treatment with antibody to eliminate RT6+ T cells, would otherwise have become diabetic. The susceptibility of EFA-deprived DP-BB rats to spontaneous diabetes was restored when they were given dietary supplements of linoleate at 70 d of age (during the usual period of susceptibility), but not when they were repleted beginning at 120 d (after the peak incidence of diabetes). EFA deficiency did lead to growth retardation, but calorically restricted control rats demonstrated that the protective effect of the deficiency state was not a function of decreased weight. To examine the relationship between the biochemical changes of EFA deficiency and its physiological effects in this system, we compared the fatty acid changes that occurred in EFA-deficient animals that did and did not develop diabetes. Nondiabetic animals had significantly lower levels of (n-6) fatty acids (i.e., linoleate and arachidonate) and higher levels of oleate, an (n-9) fatty acid, than did diabetic animals. Levels of 20:3(n-9), the fatty acid that uniquely characterizes EFA deficiency, were similar in both groups, however. Among diabetic EFA-deficient rats, the age at onset of diabetes was found to correlate inversely with the level of (n-6) fatty acids, the least depleted animals becoming diabetic earliest, whereas there was no correlation with levels of 20:3(n-9). Among animals repleted with linoleate beginning at 70 d, restoration of susceptibility to diabetes correlated with normalization of the level of arachidonate. In summary, EFA deprivation reduced the frequency of diabetes in both DP and RT6-depleted DR-BB rats. This protective effect was strongly associated with depletion of (n-6) fatty acids, particularly arachidonate, but not with accumulation of the abnormal 20:3(n-9). Conjecturally, arachidonate and/or a metabolite may play a key role in mediating inflammatory injury in this animal model of autoimmune diabetes. PMID- 2307933 TI - Naive and memory T cells show distinct pathways of lymphocyte recirculation. AB - In this report, we have addressed two questions concerning immunological memory: the way in which naive and memory T cells recirculate through the body, and the intrinsic rate of division within the naive and memory populations. We identified naive and memory T cells in sheep by their cell surface phenotype and their ability to respond to recall antigen. Memory T cells were CD2hi, CD58hi, CD44hi, CD11ahi, and CD45R-, as pertains in man. T cells that crossed from blood to the tissues of the hind leg and accumulated in the popliteal afferent lymph were all of memory phenotype. Conversely, T cells in efferent lymph, 90% of which entered the lymph node (LN) via high endothelial venules (HEV), were mostly of the naive phenotype (CD2lo, CD58lo, CD44lo, CD11alo, and CD45R+). The marked enrichment of these two phenotypes in different recirculatory compartments indicated that memory T cells selectively traffic from blood to peripheral tissues to LN (via afferent lymph), whereas naive T cells selectively traffic from blood to LN (via HEV). We argue that the differential use of these two recirculation pathways probably optimizes lymphocyte interactions with antigen. The nonrandom distribution of T cell subsets in various recirculatory compartments may be related to the relative proportion of memory cells in each subset. In particular, gamma/delta T cells in blood were almost exclusively of memory phenotype, and accumulated preferentially in afferent, but not in efferent, lymph. Finally, using the bromo-deoxyuridine labeling technique, we found that at least a sizeable proportion of memory T cells, whether in blood or afferent lymph, were a dividing population of cells, whereas naive T cells were a nondividing population. This result supports an alternative model of lymphocyte memory that assumes that maintenance of memory requires persistent antigenic stimulation. PMID- 2307934 TI - Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily. AB - IL-4, a pleiotropic cytokine produced by T lymphocytes, plays an important role in immune responsiveness by regulating proliferation and differentiation of a variety of lymphoid and myeloid cells via binding to high affinity receptors. In this report we describe the isolation and functional expression of a human IL-4-R cDNA. When transfected into COS-7 cells, the cDNA encodes a 140-kD cell-surface protein. After transfection into a murine T cell line, the cDNA encodes a protein that binds human IL-4 with high affinity and can confer responsiveness to human IL-4. The predicted extracellular domain of the IL-4-R exhibits significant amino acid sequence homology with the beta subunit of the IL-2-R (p75), and the receptors for IL-6, erythropoietin, and prolactin. These receptors comprise a novel superfamily with extracellular domains characterized by four conserved cysteine residues and a double tryptophan-serine (WSXWS) motif located proximal to the transmembrane region. PMID- 2307935 TI - Association between protective efficacy of anti-lipopolysaccharide (LPS) antibodies and suppression of LPS-induced tumor necrosis factor alpha and interleukin 6. Comparison of O side chain-specific antibodies with core LPS antibodies. AB - Two-core LPS antibodies, the rabbit J5 polyclonal antiserum and the human anti lipid A IgM mAb HA-1A, did not improve the survival of mice challenged with E. coli O111 or P. aeruginosa 3, or with the LPS extracted from them, and did not decrease the incidence of Shwartzman reactions in rabbits challenged with O111 LPS. In contrast, O side chain-specific rabbit antisera were protective in these models. The protection afforded by O side chain-specific antisera against endotoxin lethality was associated with decreased LPS-induced serum TNF and IL-6 levels, whereas core LPS antibodies had no effect on TNF or IL-6 levels. The absence of reduction of LPS-induced cytokines levels by core LPS antibodies suggests that these antibodies are not able to prevent the interactions between LPS and target cells. PMID- 2307936 TI - Specialized functions of MHC class I molecules. I. An N-formyl peptide receptor is required for construction of the class I antigen Mta. AB - Maternally transmitted factor (Mtf) is a mitochondrial gene that controls the antigenic polymorphism of the MHC class I maternally transmitted antigen (Mta). Synthetic peptides from the NH2 terminus of the mitochondrially encoded NADH dehydrogenase subunit 1 (ND1) mimic Mtf peptide activity in an allele-specific manner. We show that the minimal ND1-alpha peptide length recognized by Mtaa specific polyclonal CTLs was between 8 and 12 amino acids, while some Mtaa specific CTL clones recognized a six amino acid peptide. The N-formyl group at the NH2 terminus of ND1 was essential for Mta activity. Competition experiments using N-substituted ND1-alpha peptides showed that an N-formyl peptide receptor on the target cell, which differs from the chemotactic peptide receptor, was required for Mta expression. The specificity of this receptor can account for the distinct immune restriction of Mta in which Mtf peptides are uniquely restricted by Hmt. It is possible that the Hmt gene product is the N-formyl peptide receptor itself and that it represents a class I antigen presentation molecule specialized for binding, transport, and immune presentation of N-formyl-peptide antigens of mitochondrial and prokaryotic origin. PMID- 2307937 TI - Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities. AB - The present study demonstrates that immune tolerance can be achieved in the thymus both by clonal deletion and by clonal inactivation, but that the two tolerant states are induced by cellular elements with different radiation sensitivities. TCR engagement of self antigens on bone marrow-derived, radiation sensitive (presumably dendritic) cells induces clonal deletion of developing thymocytes, whereas TCR engagement of self antigens on radiation-resistant cellular elements, such as thymic epithelium, induces clonal anergy. The nondeleted, anergic thymocytes can express IL-2-Rs but are unable to proliferate in response to either specific antigen or anti-TCR antibodies, and do develop into phenotypically mature cells that emigrate out of the thymus and into the periphery. PMID- 2307939 TI - Early toilet training. PMID- 2307938 TI - A novel addition to the T cell repertory. Cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells. AB - Expression of the pluripotent molecule TNF in a focused and antigen-restricted fashion might provide an advantage to the host organism. Given the central role of T cells in antigen-specific immunity, we examined whether activated T cells express TNF on their cell surface. FACS analysis of highly purified normal human T cells labeled with an anti-TNF mAb revealed that T cells express cell surface TNF when signaled with the synergistic combination of a calcium ionophore, ionomycin, and a protein kinase C activator, 12-o-tetradecanoyl phorbol acetate. Cell surface radioiodination studies of stimulated T cells demonstrated the presence of 26-kD transmembrane protein, a size predicted by TNF cDNA and different from that of the 17-kD secreted TNF molecule. The induced cell surface expression of TNF could be blocked with cyclosporine and/or methylprednisolone, and Northern analysis for TNF-specific transcripts revealed that this inhibitory effect occurs pretranslationally. Our demonstration for the first time that stimulated normal human T cells display cell surface TNF provides a mechanistic basis for the realization of effects of TNF in an antigen-specific fashion. PMID- 2307940 TI - Reducing the exposure of children to environmental tobacco smoke. An office-based intervention program. AB - It is important for the family physician to consider a spectrum of screening tests, counseling topics, and childhood immunizations when providing acute and chronic care, in addition to well-child care. The effectiveness of specific clinical preventive services in eliciting positive health outcomes and age related guidelines to prioritize health promotion activity have recently been reviewed by the US Preventive Services Task Force. Given recent studies identifying environmental tobacco smoke as a risk factor for children by being associated with an increase in the incidence and severity of respiratory tract and ear infections, family physicians should be routinely screening parents, especially during visits that provide teachable moments for counseling and intervention. Family physicians need to be aware of possible responses parents may have to their counseling and provide nonjudgmental information and guidance throughout a child's early years of development. PMID- 2307941 TI - The validation of the biopsychosocial model. PMID- 2307942 TI - Lack of difference in neonatal mortality between blacks and whites served by the same medical care system. AB - To study the influence of health care systems on racial differences in low birthweight and neonatal mortality, an historical cohort analysis was conducted using birth and linked birth and death certificates of infants delivered in Pierce County, Washington, between 1982 and 1985. Overall, black infants had significantly higher rates of low birthweight than white infants. Black infants served by civilian medical care had approximately twice the neonatal mortality of white infants; however, black infants born in the military hospital had a neonatal mortality rate comparable to white infants. Controlling for marital status, age, parity, and income status did not appreciably change these patterns. Military care appeared to be associated with a protective effect for neonatal mortality for blacks. This effect was not due to differences in birthweight distribution or to the quantity of prenatal care received. The effect was most prominent for normal weight black infants, especially for those from low-income census tracts. The findings have possible implications for pediatric access issues for the poor and for the family practice model of perinatal care continuity. PMID- 2307943 TI - Have you been taking your pills? The adherence-monitoring sequence in the medical interview. AB - This paper employs qualitative, sociolinguistic techniques to identify and describe the kinds of conversational strategies that primary care physicians use to assess patient adherence to antihypertensive regimens. Three general approaches are described: indirect inquiry, simple direct questions, and information-intensive inquiry. The strengths and weaknesses inherent in these discourse categories are discussed. Qualitative assessment, coupled with the results of a pilot study investigating the effectiveness of naturally occurring instances of these three general styles, leads to the conclusion that how one asks "Have you been taking your medications?" is consequential for the accurate diagnosis and management of adherence problems. PMID- 2307944 TI - Focusing the preparticipation sports examination. AB - Athletic preparticipation evaluations are among the most common routine health screening tools, yet no standardized approach to these evaluations has been adopted. This paper presents a focused preparticipation examination form developed by the authors with the assistance of the North Carolina Academy of Family Physicians' Task Force on Sports Medicine. After reviewing the major studies of preparticipation examinations, 11 basic questions that identify specific risks for sports participation were selected. Three specific components form the core of the physical examination: blood pressure measurement, a comprehensive orthopedic examination, and cardiovascular auscultation. Other portions of the physical examination may be included because of sport-specific risks or problems identified in the history, but are not routine. The rationale for this form and guidelines for the physician to make recommendations for sports participation and timing of reevaluation are discussed. PMID- 2307945 TI - Family physician beliefs about cancer screening. Development of a survey instrument. AB - To improve rates at which physicians provide cancer control procedures, it is first necessary to identify physician and environmental characteristics that explain variations in those rates. This study used an attitude-behavior model as a guiding framework to identify beliefs, sources of influence, facilitating conditions, and critical events that may be important determinants of physicians' rates for providing eight cancer control activities. Open-ended, semistructured interviews were conducted with 26 family physicians to discuss the factors that may have affected their policies for providing each of the eight cancer control activities. Content analysis of those interviews produced unique lists of beliefs, sources of influence, facilitating conditions, and critical events for each activity. These lists of factors are more comprehensive than those identified in previous studies. A questionnaire has been developed based on these findings, and a validation study is being conducted to identify the factors that best explain variation in rates at which cancer control activities are performed. PMID- 2307946 TI - Development of a psychosocial concern index from videotaped interviews of nurse practitioners and family physicians. AB - The delivery of primary health care involves a complex interactive process between the provider and patient. One important feature of this interaction is provider concern for psychosocial issues. A study was undertaken to examine provider's actions with the patient and to describe the factors influencing the provider's concern with psychosocial issues. A total of 412 provider-patient clinic visits, including 276 with physicians and 136 with nurse practitioners, were videotaped and analyzed using a provider psychosocial concern index developed specifically for this study. Data from exit and follow-up interviews with patients plus a provider questionnaire were analyzed to identify factors associated with a provider's psychosocial concern. The results show that an interactional analysis focusing on clinician activities can be useful in describing important process-outcome relationships such as psychosocial concern. Factors such as type of visit, visit history, type of provider, and sex of patient and provider were associated with the amount of psychosocial concern displayed by providers and perceived by patients. PMID- 2307947 TI - Withdrawal from maternity care. A comparison of family physicians in Ontario, Canada, and the United States. AB - To determine the relative importance of factors influencing the withdrawal of family physicians from maternity care, two studies, one done in Ontario, Canada, and the other done in the United States, were compared. The proportion of residency-trained family physicians who provide maternity care at the initiation of their careers and the proportion who have given up maternity care are nearly identical in the United States and Canada. Both studies found that about one half of the family physicians who currently provide maternity care were giving consideration to stopping. The reasons underlying this withdrawal were multifactorial. Malpractice issues were the predominant concern of United States family physicians, but the data from the studies indicate that other issues, such as interference with lifestyle and office practice and the effect of attitudes of obstetricians, should not be overlooked. PMID- 2307948 TI - Thioridazine-induced non-icteric hepatotoxicity. Report of a case. PMID- 2307949 TI - The family physician and smoking in pregnancy. PMID- 2307950 TI - The perceived need for physician management training. PMID- 2307951 TI - Treatment of hemorrhoids. PMID- 2307952 TI - Citywide neonatal program. Ten years experience. AB - A citywide neonatal program initiated in Jacksonville, Florida, in July 1978 through December 1988 had incorporated all six hospitals that provide obstetrical services in the metropolitan area. Admissions, occupancy rate, as well as patient care days served by the Regional Perinatal Intensive Care Center (RPICC) and the Level II nurseries have increased to capacity. More "step-down" care beds are made available by this program which has also proved to be cost effective. Areas of concern are discussed. PMID- 2307954 TI - Are we becoming a police state? PMID- 2307953 TI - Trimming the excess of the health care system. PMID- 2307955 TI - Doctors eat quiche and they become wimps and grunts. PMID- 2307956 TI - Correction of reentrant atrioventricular tachycardia by surgical ablation of accessory pathways. AB - Patients with reentrant atrioventricular (AV) tachycardia have an accessory connection in addition to the normal conduction pathway, AV node and His-Purkinje system. This pathway predisposes some patients to recurrent, disabling supraventricular tachyarrhythmias. Although it is found with other associated cardiac conditions, most patients are healthy with no underlying structural heart disease. Interest has developed in surgically dividing the accessory pathway in patients with arrhythmias poorly controlled with medications or at risk for potentially fatal tachyarrhythmias. Surgery is safe and effective and should be considered for patients with rapid AV conduction during atrial fibrillation, those refractory to pharmacologic therapy, and young patients who otherwise would require lifelong antiarrhythmic therapy. This report describes surgical correction of reentrant AV tachycardia in five patients ranging in age from six months to 23 years. PMID- 2307957 TI - Inadvertent cervical cord puncture during myelography via C1-C2 approach. AB - C1-C2 puncture is a procedure commonly performed to assure satisfactory cervical myelography. Cord injury with neurological deficit has been reported following intramedullary injection of myelographic contrast material. We report a case of inadvertent intramedullary injection of metrizamide which was initially discovered during postmyelographic CT scanning. The patient had very minimal symptoms during the procedure and had no immediate or long-term complications. PMID- 2307958 TI - Efferent control of temporal response properties of the Limulus lateral eye. AB - The sensitivity of the Limulus lateral eye exhibits a pronounced circadian rhythm. At night a circadian oscillator in the brain activates efferent fibers in the optic nerve, inducing multiple changes in the physiological and anatomical characteristics of retinal cells. These changes increase the sensitivity of the retina by about five orders of magnitude. We investigated whether this increase in retinal sensitivity is accompanied by changes in the ability of the retina to process temporal information. We measured the frequency transfer characteristic (FTC) of single receptors (ommatidia) by recording the response of their optic nerve fibers to sinusoidally modulated light. We first measured the FTC in the less sensitive daytime state and then after converting the retina to the more sensitive nighttime state by electrical stimulation of the efferent fibers. The activation of these fibers shifted the peak of the FTC to lower frequencies and reduced the slope of the low-frequency limb. These changes reduce the eye's ability to detect rapid changes in light intensity but enhance its ability to detect dim flashes of light. Apparently Limulus sacrifices temporal resolution for increased visual sensitivity at night. PMID- 2307959 TI - Phosphorylation modulates potassium conductance and gating current of perfused giant axons of squid. AB - The presence of internal Mg-ATP produced a number of changes in the K conductance of perfused giant axons of squid. For holding potentials between -40 and -50 mV, steady-state K conductance increased for depolarizations to potentials more positive than approximately -15 mV and decreased for smaller depolarizations. The voltage dependencies of both steady-state activation and inactivation also appears shifted toward more positive potentials. Gating kinetics were affected by internal ATP, with the activation time constant slowed and the characteristic delay in K conductance markedly enhanced. The rate of deactivation also was hastened during perfusion with ATP. Internal ATP affected potassium channel gating currents in similar ways. The voltage dependence of gating charge movement was shifted toward more positive potentials and the time constants of ON and OFF gating current also were slowed and hastened, respectively, in the presence of ATP. These effects of ATP on the K conductance occurred when no exogenous protein kinases were added to the internal solution and persisted even after removing ATP from the internal perfusate. Perfusion with a solution containing exogenous alkaline phosphatase reversed the effects of ATP. These results provide further evidence that the effects of ATP on the K conductance are a consequence of a phosphorylation reaction mediated by a kinase present and active in perfused axons. Phosphorylation appears to alter the K conductance of squid giant axons via a minimum of two mechanisms. First, the voltage dependence of gating parameters are shifted toward positive potentials. Second, there is an increase in the number of functional closed states and/or a decrease in the rates of transition between these states of the K channels. PMID- 2307960 TI - Basolateral membrane Na(+)-independent Cl-/HCO3- exchange in the inner stripe of the rabbit outer medullary collecting tubule. AB - The inner stripe of the outer medullary collecting tubule is a major distal nephron segment in urinary acidification. To examine the mechanism of basolateral membrane H+/OH-/HCO3- transport in this segment, cell pH was measured microfluorometrically in the inner stripe of the rabbit outer medullary collecting tubule perfused in vitro using the pH-sensitive fluorescent dye, (2',7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein. Decreasing peritubular pH from 7.4 to 6.8 (changing [HCO3-] from 25 to 5 mM) caused a cell acidification of 0.25 +/- 0.02 pH units, while a similar luminal change resulted in a smaller cell acidification of only 0.04 +/- 0.01 pH units. Total replacement of peritubular Cl with gluconate caused cell pH to increase by 0.18 +/- 0.04 pH units, an effect inhibited by 100 microM peritubular DIDS and independent of Na+. Direct coupling between Cl- and base was suggested by the continued presence of peritubular Cl- removal-induced cell alkalinization under the condition of a cell voltage clamp (K(+)-valinomycin). In addition, 90% of basolateral membrane H+/OH-/HCO3- permeability was inhibited by complete removal of luminal and peritubular Cl-. Peritubular Cl(-)-induced cell pH changes were inhibited two-thirds by removal of exogenous CO2/HCO3- from the system. The apparent Km for peritubular Cl- determined in the presence of 25 mM luminal and peritubular [HCO3-] was 113.5 +/- 14.8 mM. These results demonstrate that the basolateral membrane of the inner stripe of the outer medullary collecting tubule possesses a stilbene-sensitive Cl /HCO3- exchanger which mediates 90% of basolateral membrane H+/OH-/HCO3- permeability and may be regulated by physiologic Cl- concentrations. PMID- 2307961 TI - Apical membrane Na+/H+ exchange in Necturus gallbladder epithelium. Its dependence on extracellular and intracellular pH and on external Na+ concentration. AB - Intracellular microelectrode techniques and extracellular pH measurements were used to study the dependence of apical Na+/H+ exchange on mucosal and intracellular pH and on mucosal solution Na+ concentration ([Na+]o). When mucosal solution pH (pHo) was decreased in gallbladders bathed in Na(+)-containing solutions, aNai fell. The effect of pHo is consistent with titration of a single site with an apparent pK of 6.29. In Na(+)-depleted tissues, increasing [Na+]o from 0 to values ranging from 2.5 to 110 mM increased aNai; the relationship was well described by Michaelis-Menten kinetics. The apparent Km was 15 mM at pHo 7.5 and increased to 134 mM at pHo 6.5, without change in Vmax. In Na(+)-depleted gallbladders, elevating [Na+]o from 0 to 25 mM increased aNai and pHi and caused acidification of a poorly buffered mucosal solution upon stopping the superfusion; lowering pHo inhibited both apical Na+ entry and mucosal solution acidification. Both effects can be ascribed to titration of a single site; the apparent pK's were 7.2 and 7.4, respectively. Diethylpyrocarbonate (DEPC), a histidine-specific reagent, reduced mucosal acidification by 58 +/- 4 or 39 +/- 6% when exposure to the drug was at pHo 7.5 or 6.5, respectively. Amiloride (1 mM) did not protect against the DEPC inhibition, but reduced both apical Na+ entry and mucosal acidification by 63 +/- 5 and 65 +/- 9%, respectively. In the Na(+)-depleted tissues mean pHi was 6.7. Cells were alkalinized by exposure to mucosal solutions containing high concentrations of nicotine or methylamine. Estimates of apical Na+ entry at varying pHi, upon increasing [Na+]o from 0 to 25 mM, indicate that Na+/H+ exchange is active at pHi 7.4. Intracellular H+ stimulated apical Na+ entry by titration of more than one site (apparent pK 7.1, Hill coefficient 1.7). The results suggest that external Na+ and H+ interact with one site of the Na+/H+ exchanger and that cytoplasmic H+ acts on at least two sites. The external titratable group seems to be an imidazolium, which is apparently different from the amiloride-binding site. The dependence of Na+ entry on pHi supports the notion that the Na+/H+ exchanger is operational under normal transport conditions. PMID- 2307962 TI - Protection against rabies in mice by a cytotoxic T cell clone recognizing the glycoprotein of rabies virus. AB - By the use of liposomes containing the purified surface glycoprotein (G) of rabies virus and the haemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of Sendai virus, the target antigen of anti-rabies virus cytotoxic T lymphocyte (CTL) clones isolated in a previous study was identified as the G protein. Recognition of the H-2K determinant of the class I major histocompatibility complex (MHC) was necessary for target lysis by the CTL clones. One of the CTL clones was examined for the ability to protect mice against a lethal rabies virus infection. CTL were transferred into syngeneic mice which had been infected in the hind footpad with the ERA strain of rabies virus. The infection was converted into a lethal infection by cyclophosphamide treatment 1 day after virus infection. Transfer of CTL 2 to 3 days after virus infection protected approximately 50% of mice during the observation period of 4 weeks. Greater protection was obtained in mice receiving both anti-rabies virus antibodies and CTL cells. PMID- 2307963 TI - Sequence of the large double-stranded RNA segment of the N1 strain of infectious pancreatic necrosis virus: a comparison with other Birnaviridae. AB - The cDNA sequence of the large dsRNA segment (segment A) of the N1 strain of infectious pancreatic necrosis virus (IPNV) has been determined. The nucleotide and deduced amino acid sequences were compared to the sequences of segment A of the Jasper strain of IPNV and to the sequences of segments A and B (5' and 3' flanking regions) of the 002-73 strain of infectious bursal disease virus (IBDV). The comparison demonstrated that the precursor protein of the major structural polypeptide, pVP2, is highly conserved at the N and C termini, whereas the amino acid sequence of an internal segment shows greater diversity between the strains. This internal segment probably carries the serotype-specific epitopes of birnaviruses. An alternative open reading frame (ORF) (444 bp) partly overlapping with the large ORF (2916 bp) of segment A was found to be conserved among the IPNV strains and is probably also present in the 002-73 strain of IBDV. This small ORF may encode a novel birnavirus polypeptide with an Mr of 17K. SDS-PAGE of radiolabelled purified IPNV particles revealed a band corresponding to the possible novel 17K polypeptide. Short terminal inverted repeats are found in segment A of the N1 and Jasper strains of IPNV and in segment B of the 002-73 strain of IBDV. Segment A of IPNV and segment B of IBDV also contain adjacent inverted repeats at their 5'-terminal flanking regions. PMID- 2307964 TI - Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis. AB - Twelve long-term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-1) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long-term interleukin-2-dependent cell lines exhibited a pattern characteristic of CD4(+)-activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were never detected in uncultured PBMC, but they were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50% of the cells exhibited HTLV-I antigens by IF. However, numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high Mr polypeptides were detected by Western blot in cell lysates when comparing TSP- or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46. PMID- 2307965 TI - Molecular cloning and physical mapping of the DNA of bovine adenovirus serotype 4; study of the DNA homology among bovine, human and porcine adenoviruses. AB - The DNA of bovine adenovirus (BAV) serotype 4, a member of the subgroup 2 BAVs, has been cloned and mapped with 11 restriction enzymes. Southern blot hybridizations probed by a clone containing about 50% of the BAV-4 genome revealed a very strong and extended DNA sequence homology amongst the members of subgroup 2, but no homology was detectable to the subgroup 1 bovine, or any of those human (HAV) and porcine adenovirus serotypes examined. These findings were strengthened by reciprocal hybridizations. When using the cloned hexon gene region of BAV-3 (subgroup 1) or the total genome of HAV-2 as probes, again no homology could be shown to the bovine subgroup 2 serotypes. The extent of DNA homology detectable between the members of bovine subgroup 1, the porcine and the human serotypes was variable, but in general less expressed than that observed within the bovine subgroup 2. PMID- 2307967 TI - The DSM-IV (depression) classification: to be or not to be? AB - In 1958, when I started my residency training in psychiatry, diagnostic confusion reigned in the realm of depressive disorders. Diagnostic concepts were not operationalized, nomenclature was not standardized, and no taxonomy was generally accepted. What is the situation today, some 30 years later? Today we work under the patronage of the DSM-III classification of depression, a system in which diagnostic concepts are operationalized, nomenclature is standardized, and this nomenclature is officially accepted in the United States and de facto accepted in numerous countries all over the world. Did that system provide order where chaos reigned? The answer has to be in the negative. PMID- 2307966 TI - Sequence comparison of the phosphoprotein mRNAs of antigenic subgroups A and B of human respiratory syncytial virus identifies a highly divergent domain in the predicted protein. AB - The sequences of the P mRNA and protein of strain 18537 of antigenic subgroup B of human respiratory syncytial virus were determined by sequencing cloned cDNAs of intracellular mRNA. Comparison with the corresponding sequences of the A2 strain of subgroup A showed that there was extensive sequence identity at both the nucleotide (80% identity) and amino acid (90% identity) levels. The P proteins contained a single divergent region (52% amino acid identity) flanked by highly conserved domains (96% identity). The previously observed differences in electrophoretic mobilities between the P proteins of subgroup A strains and certain subgroup B strains could not be attributed to differences in the polypeptide Mr of the primary translation product. PMID- 2307968 TI - Immigration, stress, and depressive symptoms in a Mexican-American community. AB - This study assessed levels of depressive symptomatology in a household probability sample of Mexico-born (N = 706) and U.S.-born (N = 538) Mexican Americans. We hypothesized that immigration status differences in acculturation, strain, social resources, and social conflict, as well as differences in the associations of these variables with depression, would account for differences in depression between U.S.-born and Mexico-born respondents. U.S.-born Mexican Americans had higher depression scores than those born in Mexico. When cultural and social psychological variables were controlled in a multiple regression analysis, the immigrant status difference persisted. Tests of interaction terms suggested greater vulnerability to the effects of low acculturation and low educational attainment among the U.S.-born relative to those born in Mexico; however, the immigrant status difference persisted after controlling for these interactions. Unmeasured variables such as selective migration of persons with better coping skills, selective return of depressed immigrants, or generational differences in social comparison processes may account for the immigration status difference. PMID- 2307969 TI - DSM-III-R subtypes of social phobia. Comparison of generalized social phobics and public speaking phobics. AB - Social phobic patients who fear most or all social interaction situations are labeled generalized social phobics in DSM-III-R. Thirty-five patients who met this criterion were compared with 22 social phobic patients whose fears were restricted to public speaking situations. Generalized social phobics were younger, less educated, and less likely to be employed, and their phobias were rated by clinical interviewers as more severe than those of public speaking phobics. Generalized social phobics appeared more anxious and more depressed and expressed greater fears concerning negative social evaluation. They performed more poorly on individualized behavioral tests and differed from public speaking phobics in their responses to cognitive assessment tasks. The two groups showed marked differences in their patterns of heart rate acceleration during the behavioral test. The implications of these findings for the classification and treatment of social phobic individuals are discussed. PMID- 2307970 TI - Panic attacks and related disorders in alcohol-dependent, depressed, and nonclinical samples. AB - Although several studies have indicated that a substantial portion of alcoholics have an anxiety disorder, relatively little information exists specifically regarding panic disorders. In addition, prior studies have been marred by the absence of appropriate contrast groups. The present investigation compared the lifetime prevalence of panic attacks and panic-related disorders diagnosed according to DSM-III criteria in a group of 79 alcohol-dependent patients, 64 depressed patients, and 70 nonclinical subjects. Panic attacks, panic disorder, and agoraphobia with panic attacks were more prevalent in the alcohol-dependent and depressed samples than among nonclinical subjects. Men in both clinical samples were more likely than women to have had nonagoraphobic panic disorder, but male alcoholics were less likely to have developed agoraphobia than were female alcoholics or depressed patients of either sex. No consistent chronological relationship between onset of panic attacks and alcohol abuse was found. Results indicate that there is an unusually high prevalence of panic attacks and panic-related disorders among alcoholics, but comparable prevalence rates can be found in depressed and perhaps some other psychiatric populations. Implications for the assessment and treatment of alcohol-dependent and panic disordered patients are discussed. PMID- 2307971 TI - Backward masking as a function of spatial frequency. A comparison of MMPI identified schizotypics and control subjects. AB - The present investigation relied upon a neurophysiological explanation of visual masking and compared the backward masking susceptibility of hypothetical schizotypal individuals with that of control subjects. Masking functions were assessed within two masking conditions: high spatial frequency (HSF) and low spatial frequency (LSF). Schizotypal subjects (those with a 2-7-8 or an 8-9 MMPI profile type) were compared with "psychiatric" control subjects (those with a spike 9 or a 4-9 profile type) and normal control subjects. Group differences were expected only in the transient-facilitating, LSF masking condition in this study's assessment of the hypothesis that a transient channel abnormality underlies the schizophrenia spectrum backward masking deficit. As predicted, schizotypal subjects displayed greater masking susceptibility in the LSF transient-facilitating condition as compared with the HSF, sustained-facilitating condition that produced no group differences. These results suggest that multichannel neurophysiological models of masking may help to direct research designed to gain an increased understanding of the specific nature of the spectrum masking deficit. PMID- 2307972 TI - Diagnosing personality disorders in recent-onset schizophrenia. AB - The present study aimed to determine the prevalence of personality disorders (PDs) and personality disorder traits in 40 recent-onset schizophrenic patients, to establish the degree of concordance between the Structured Interview for DSM III Personality Disorders (SIDP) and the Million Multiaxial Clinical Inventory (MCMI-I), and to examine the interrater reliabilities for the diagnosis of SIDP disorders and traits. During their recovery phase, patients underwent the SIDP and completed the MCMI-I, a self-report inventory. Results showed that 57% of all patients had PDs according to the SIDP. The most common PDs were antisocial, borderline, and schizotypal, whereas the most common according to the MCMI-I were dependent, narcissistic, and avoidant. Both instruments indicated that multiple PD diagnoses were common. Paranoid and schizotypal traits were found to be ubiquitous across instruments. The level of agreements between the two instruments was poor on diagnostic assignment but better when trait scores were considered. PMID- 2307973 TI - Gender differences in the clinical features of unipolar major depressive disorder. AB - Gender differences in the presence or absence and the severity of forty-seven clinician-rated features of depression were examined, controlling for the sex of the rater. Subjects consisted of 498 moderately to severely depressed patients coming for treatment and diagnosed as suffering from nonpsychotic, unipolar major depressive disorder. Significant differences were found only for increased appetite and weight. No differences were observed in endogenous symptoms, global severity of depression, or impairment in functioning. The results indicate that, although the rate of major depressive disorder is greater in women, its symptomatology is relatively homogeneous with regard to gender. PMID- 2307974 TI - Alprazolam and withdrawal seizures. PMID- 2307975 TI - Ocular dominance stripe formation by regenerated isogenic double temporal retina in Xenopus laevis. AB - In lower vertebrates such as frogs and fish, long ocular dominance stripes with anterior-posterior (A-P) orientation can be produced by causing both eyes to innervate one optic tectum during the course of development. Similar experiments on adult animals usually produce patches rather than stripes. During development, new retinal fibers from the nasal retina segregate into appropriate stripes at the growing edge of the posterior (P) tectum while new temporal fibers segregate at the non-growing anterior (A) tectal edge. Fiber segregation into long A-P oriented stripes might depend upon a template produced by new nasal fibers initiating stripe orientation in the vicinity of new tectal cells; new nasal fibers would orient to the nascent (posterior) edge of the template while temporal fibers would orient to the anterior (non-growing) end of the template. To test the dependence of stripe formation on the matching of nascent retinal cells with nascent tectal cells, we compared stripe orientation in animals with isogenic double nasal innervation and isogenic double temporal innervation of the tectum. In double nasal innervation, the oldest retinal cells innervate the anterior tectum; new fibers from the entire retinal periphery always innervate the newest tectal cells at the posterior tectum. Stripes are oriented A-P, consistent with a maturation front model. In contrast, the oldest retinal cells innervate the newest (posterior) tectal cells in double temporal innervation of the tectum; the growing retinal periphery innervates the non-growing anterior tectum. Stripes are also oriented A-P, indicating that the production of long stripes does not depend upon maturation front matching of nascent retinal fibers and nascent tectal cells. PMID- 2307976 TI - Depolarization regulates expression of a synaptic vesicle protein in rat superior cervical ganglia in vitro. AB - The role of membrane depolarization in the regulation of expression of a neuron specific protein was evaluated by culturing superior cervical ganglia from neonatal rats in defined medium and manipulating neuronal activity by depolarizing agents. P65 is an integral membrane protein of synaptic vesicles and can be used as a marker for general neuronal maturation. P65 antigen levels were quantified by indirect radioimmunoassay, using monoclonal antibodies. The expression of p65 in ganglion explants increased by 40-100% when the cultures were treated with the depolarizing agents, veratridine or high potassium. The veratridine effect could be blocked by simultaneous treatment with the sodium channel blocker, tetrodotoxin (TTX). The rise in p65 was not evident until 36 h after depolarizing treatment had begun and reached peak levels after 48 h, with no further increases observed with sustained treatment. After removal of the depolarizing treatment, p65 levels returned to control values after 24 h. P65 joins a growing number of molecules whose expression is regulated by membrane depolarization. PMID- 2307977 TI - Development and survival of thoracic motoneurons and hindlimb musculature following transplantation of the thoracic neural tube to the lumbar region in the chick embryo: anatomical aspects. AB - Thoracic spinal cord transplanted to the lumbar region at the time of neural tube closure in the chick embryo survives and initially differentiates normally similar to in situ thoracic cord. Normal numbers of motoneurons are produced that innervate the host hindlimb musculature. In control thoracic cord approximately 70% of the motoneurons are lost by normal cell death between embryonic day (E) 6 and E11-E12. By contrast, the transplanted thoracic cord loses only about 30% of the motoneurons during this period. Transplantation of one hindlimb to the thoracic region also reduces the normal loss of in situ thoracic motoneurons. We conclude that some factor(s) associated with the increased target size provided by the hindlimbs promotes the survival of thoracic motoneurons. In contrast, by E16-E18 motoneuron numbers in the thoracic transplants decrease to below control levels. Dorsal root ganglion cells in the transplant were also initially increased (on E8) but later decreased to below control values. Hindlimb muscles innervated by thoracic motoneurons in the transplant also differentiated normally up to E10 to E12. Myotube size and numbers, muscle size and myotube types (fast versus slow) all developed normally in several thoracically-innervated hindlimb muscles. However, beginning on E14 myotube numbers and muscle size were markedly decreased resulting in muscle atrophy. Injections of horseradish peroxidase (HRP) into the thoracic transplants labelled neurons in the host spinal cord and brainstem rostral to the transplant thereby indicating an anatomical continuity between host and transplant neural tube. Injections of HRP into specific thoracically innervated hindlimb muscles on E8 labelled distinct pools of motoneurons in the transplants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2307978 TI - Development and survival of thoracic motoneurons and hindlimb musculature following transplantation of the thoracic neural tube to the lumbar region in the chick embryo: functional aspects. AB - Following heterotopic transplantation of the thoracic neural tube to the lumbar region on embryonic day (E) 2, the transplanted cord differentiates normally and establishes neuroanatomical connections with the host central nervous system and hindlimb muscles. Beginning on about E12, however, the neuromuscular system begins to undergo regressive changes resulting in motoneuron degeneration and muscle atrophy (O'Brien and Oppenheim, 1990). In the present paper, we have examined the development of neuromuscular function in thoracic transplant embryos from E6 to the time of hatching on E20-21. The onset of hindlimb movements and reflexes occurred at the same time (E6-E8) in both control and thoracic transplant embryos. Further, both the nature (pattern) and frequency of these movements appeared normal in the thoracic transplants up to E10-E12, after which there was a gradual and marked reduction in the frequency, and an alteration in the pattern, of both spontaneous and reflex-evoked hindlimb movements. After E16 normal movements were virtually absent in many of the thoracic transplant cases. By contrast, movements of the head, trunk and wings were normal in these embryos throughout the observation period. Hindlimbs innervated partly by the thoracic transplant and partly by remaining host lumbar cord did not exhibit the regressive changes in function after E10 that occurred in hindlimbs innervated exclusively by the thoracic transplant. EMG recordings from specific hindlimb muscles innervated solely by thoracic motoneurons demonstrated that the activation pattern of both flexors and extensors was similar to the repetitive pattern observed in normal thoracically innervated intercostal muscles (i.e., extensor-like). Muscles did not show distinguishable EMG burst patterns with inhibitory periods as do control lumbar innervated muscles. We conclude that the development of the pattern generating circuitry in the transplanted thoracic cord was similar to normal thoracic cord and thus appeared to be uninfluenced by having contacted the foreign hindlimb muscle targets early in development. Activity blockade with curare from E6 to E14 suppressed the loss of motoneurons that occurs in the thoracic transplant after E10. Thus, the abnormal thoracic like activation pattern of thoracically innervated hindlimbs may be a critical signal in the initiation of the neuromuscular regression that occurs after E10 in these preparations. Finally, although the innervation and formation of neuromuscular endplates in thoracic transplants appeared normal up to E12, by E14 both the intramuscular nerves and the endplates exhibited signs of degeneration and regression. Thoracic motoneurons are initially able to innervate and functionally activate hindlimb muscles in a manner similar to that of thoracically innervated intercostal muscles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2307979 TI - Establishment and characterization of multipotent neural cell lines using retrovirus vector-mediated oncogene transfer. AB - Neural cell lines were produced by retroviral vector-mediated transduction of the avian myc oncogene. Target cells were mitotic progenitor cells of postnatal mouse olfactory bulb and cerebellum, and postnatal rat cerebral cortex. Infection of the first two areas, where neurogenesis and gliogenesis occur postnatally, produced multipotent clonal lines that exhibited phenotypes of both neuronal and glial cells, and one line with a stable neuronal phenotype. Infection of cerebral cortex, where gliogenesis, but not neurogenesis, occurs postnatally, generated mortal clones that exhibited cells of glial phenotype. These lines should prove valuable for both in vitro and in vivo studies aimed at understanding the control of cell fate and differentiation of neural progenitors. PMID- 2307980 TI - Multiple sclerosis: a role for astroglia in active demyelination suggested by class II MHC expression and ultrastructural study. AB - Central nervous system (CNS) tissue was studied by immunocytochemistry and electron microscopy from three cases of multiple sclerosis (MS) in which evidence of ongoing myelin breakdown could be documented. The study focussed upon the role of glial cells in the pathogenesis of demyelination. In acute MS, demyelination involved the vesicular dissolution of myelin from intact axons and a paucity of fibrillary astrogliosis. Foamy macrophages, many of them probably derived from transformed and recently proliferated microglia, contained recognizable myelin debris and lipid droplets and were abundant throughout the lesions. These cells formed the major phagocytic population and stained positively for class II major histocompatibility complex antigens (HLA-DR; Ia). In acute MS lesions, rounded astrocytes were encountered which possessed membrane-bound compartments enclosing phagocytosed fragments of myelin basic protein-positive debris. Despite the superficial resemblance of these cells to foamy macrophages, the presence of intermediate filaments, glycogen granules and diffuse glial fibrillary acidic protein positivity supported an astroglial identity. Astrocyte processes were involved in myelin removal and invested recently demyelinated axons. Hypertrophic fibrous astrocytes were common in chronic active lesions, were capable of myelin degradation and on occasion, contained myelin debris attached to clathrin-coated pits. These astrocytes were sometimes Ia+. Oligodendrocytes were depleted from the center of active lesions but were numerous at the lesion margin, suggesting survival and proliferation. They stained positively for myelin-associated glycoprotein, a marker for immature oligodendrocytes. However, they were invariably Ia-. The findings confirm and further support a role for the astrocyte as both an antigen presenting cell and a phagocyte in the CNS during MS. PMID- 2307981 TI - Ultrastructural and immunohistologic characterization of guanethidine-induced destruction of peripheral sympathetic neurons. AB - Repeated daily injections of the adrenergic blocking agent guanethidine in high doses (50 mg/kg) to either newborn or adult rats produces a permanent sympathectomy which is thought to involve an immune-mediated mechanism. Ultrastructural examination of the acute phase of guanethidine-induced neuronal degeneration in the superior cervical ganglion demonstrated a prominent lymphocytic infiltrate in the ganglionic parenchyma and perivascular spaces. Within the satelliting cell sheath there were lymphocytes with delicate processes in intimate contact with abnormal or degenerating principal sympathetic neurons. The lymphocytic infiltrate and early evidence of neuronal degeneration developed within three days of onset of treatment and reached a maximum on the 7th day. Immunocytochemical studies of the ganglion demonstrated that the mononuclear infiltrate was composed primarily of CD-8 positive, OX-19 negative lymphocytes, which may represent a natural killer (NK) or NK-like effector cell, as well as scattered monocytes and macrophages. Guanethidine showed little effect on the prevertebral (superior mesenteric and celiac) sympathetic ganglia compared to the paravertebral (superior cervical) chain ganglia of the same animals. Considerable rat strain selectivity was noted with Lewis and Sprague-Dawley strains showing a greater degree of neuronal destruction than Fischer 344 rats. Neonatal thymectomy failed to prevent neuronal degeneration and the lymphocytic infiltrate. These features of immune neuronal killing are not typical of a characterized antibody or T-lymphocyte mediated effector mechanism, but may represent a selective NK cell or NK-like cell mediated pathogenetic pathway. Guanethidine-induced neuronal destruction appears to be a unique type of drug-induced, cell-mediated, autoimmune attack on sympathetic neurons and may provide insight into autoimmune disorders and possibly into diseases characterized by selective neuronal degeneration. PMID- 2307982 TI - Selective disconnection of specific visual association pathways in cases of Alzheimer's disease presenting with Balint's syndrome. AB - During a recent clinical and neuropathological evaluation of a large autopsy population of brains our attention was drawn to a subset of patients with Alzheimer's disease (AD) presenting with a major impairment of visuospatial skills referred to as Balint's syndrome. In this subset a shift in the distribution of certain pathological profiles had occurred in that the visual areas of the occipital and posterior parietal regions had an increased number of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in AD. Previous quantitative analyses have shown that generally in AD, primary sensory cortical areas are less damaged than association areas of the frontal and temporal lobes, as demonstrated by the laminar and regional distribution of two neuropathological features of the disease, neurofibrillary tangles and neuritic (senile) plaques. The distribution of pathological lesions in the AD cases with Balint's syndrome revealed that specific visual association pathways were disrupted, which are normally spared in AD. These data suggest that in some cases of AD, the particular psychological and neurological symptomatology may be caused by the selective loss of specific corticocortical systems, as reflected in the differential distribution of the neuropathological markers of the disease. PMID- 2307983 TI - The brain in aged elephants. PMID- 2307984 TI - Choroid plexus carcinoma in siblings. PMID- 2307985 TI - Multiple sclerosis with evidence of remyelination. PMID- 2307986 TI - The role of adjuvant surgery in the combined modality therapy of small-cell bronchogenic carcinoma after a chemotherapy-induced partial remission. AB - Twenty-six patients with a limited-disease presentation of small-cell bronchogenic carcinoma (SCBC) had surgery after achieving a partial remission with three cycles of chemotherapy. Persistent SCBC was found in 15 patients (58%), non-small-cell bronchogenic carcinoma (NSCBC) in six patients (23%), and no malignancy in five patients (19%). Twelve patients have died since surgery. Tumor-node-metastasis (TNM) staging prior to or after chemotherapy was not predictive of outcome, but an N0 status found at pathological examination of the surgical specimen was predictive of long-term survival. Median survival for this group of patients was 25 months. Adjuvant surgery is feasible and may be beneficial. PMID- 2307987 TI - Prognostic significance of surface marker expression on blasts of patients with de novo acute myeloblastic leukemia. AB - The prognostic significance of the expression of surface membrane antigens on the blasts of 123 consecutive patients with de novo acute myeloblastic leukemia (AML) was evaluated. For this purpose, reactivity of monoclonal antibodies (mAbs) CLB ERY3 (antiblood-group H antigen), VIM-D5 (CD15), WT1 (CD7), MY7 (CD13), MY9 (CD33), VID-1 (antihuman leukocyte antigen locus DR [anti-HLA DR]), VIM-2 (CDw65L), VIM-13 (CD14), 63D3 (CD14) and anti-TdT with leukemic blast cell populations was prospectively analyzed with respect to the rates of complete remission (CR), continuous complete remission (CCR), and survival. The overall rate of CR was 65%, the 6-year rates of overall CCR and survival were 23% and 13%, respectively (median period of patient observation, 30 months). Of all Abs tested, four (CLB-ERY3, MY7, anti-TdT, and VIM-D5) were found to be of prognostic value. Reactivity of CLB-ERY3, MY7, and anti-TdT was predictive for CR (CLB ERY3+, 43% v CLB-ERY3-, 73%, P less than .02; MY7+, 59% v MY7-, 91%, P less than .003; TdT+, 28% v TdT-, 71%, P less than .001, respectively) and probability of survival (significantly lower survival rates: CLB-ERY3+, P less than .02; MY7+, P less than .03; and TdT+ cases, P less than .001, respectively). Reactivity of VIM D5 was significantly associated with a higher probability of CCR (P less than .01). Our results confirm earlier reports on the prognostic significance of expression of CD13 and TdT in AML and indicate CLB-ERY3 (antiblood-group H antibody) and VIM-D5 (CD15) as further markers predictive for the clinical outcome in patients with de novo AML. PMID- 2307988 TI - Characterization of immunoglobulin and T-cell receptor gene patterns in B-cell precursor acute lymphoblastic leukemia of childhood. AB - Immunoglobulin (Ig) and T-cell receptor (TCR) genes were examined in the lymphoblasts of 70 children with immunophenotypically defined B-cell precursor acute lymphoblastic leukemia (ALL). The most frequent genes to rearrange were Ig heavy (H) chain (93%) and TCR delta (79%), followed by TCR gamma (49%), Ig kappa and/or lambda light (L) chain (46%), TCR alpha (46%), and TCR beta (29%). Thus, despite their putative "B-cell precursor" lineage, these leukemias manifest a remarkably high incidence of TCR gene rearrangements. While certain patterns predominate, there is considerable heterogeneity in Ig and TCR genotypes in this disease. No significant associations were found between Ig and TCR genotype and commonly used prognostic factors including age, sex, race, WBC, French-American British (FAB) subtype, or cytogenetics. However, the lymphoblasts of three of six patients who failed to achieve initial remission had germline patterns of every Ig and TCR gene, a genotype not observed in the leukemic cells from any of the 64 patients who achieved complete remission (p2 = .0007). This study suggests that particular Ig and TCR genotypes may be of clinical relevance in childhood B-cell precursor ALL. The finding of rearranged TCR genes in a large proportion of cases raises fundamental questions about early lineage commitment and lymphocyte differentiation along B-cell and T-cell pathways. PMID- 2307989 TI - Septicemia in pediatric oncology patients: the significance of viridans streptococcal infections. AB - One hundred nine consecutive episodes of septicemia were retrospectively evaluated in 61 children with malignancy. In addition, the records of all pediatric oncology patients who received high-dose cytarabine (HDAC) chemotherapy were reviewed. Gram-positive organisms accounted for 82.6% of the septicemic episodes. In the total group, coagulase-negative staphylococci and viridans streptococci accounted for 35.8% and 28.4% of the episodes, respectively. In granulocytopenic patients, viridans streptococci were the most common pathogens (36.8%). In the subset of patients who received HDAC, 62.5% of the septicemic episodes were caused by viridans streptococci. Pulmonary complications developed in nine (29%) of the total cases of viridans streptococcal sepsis, whereas these complications occurred in only eight (10.3%) of the septic episodes caused by other organisms. In patients who had viridans septicemia, prior treatment with HDAC did not increase the incidence of pulmonary complications. In septic children with malignancy, our results demonstrate a high incidence of gram positive organisms, including viridans streptococci, which were once regarded as culture contaminants. PMID- 2307990 TI - High-dose cytotoxic therapy and bone marrow transplantation for relapsed Hodgkin's disease. AB - Patients with Hodgkin's disease who have failed two or more chemotherapy regimens or who have relapsed after an initial chemotherapy-induced remission of less than 12 months are seldom cured with conventional salvage therapies. We studied the effect of high-dose cytoreductive therapy followed by bone marrow transplantation in 50 such patients with relapsed Hodgkin's disease. Twenty-one patients with histocompatibility locus antigen (HLA)-matched donors had allogeneic marrow transplants, one patient received marrow from an identical twin, and 28 patients without a matched donor received autologous grafts purged with 4 hydroperoxycyclophosphamide. Busulfan plus cyclophosphamide was the preparative regimen for the 25 patients who had received extensive prior irradiation, and the other 25 patients received cyclophosphamide plus total body irradiation. The overall actuarial probability of event-free survival at 3 years was 30%, with a median follow-up of 26 months. The event-free survival following transplantation was influenced by the number of chemotherapy failures and the patient's response to conventional salvage therapy prior to transplant. The 16 patients who were transplanted at first relapse, while still responsive to standard therapy, had a 64% actuarial probability of event-free survival at 3 years. Age, presence of extranodal disease, preparative regimen, and type of graft (autologous v allogeneic) were not significant prognostic factors. The majority of transplant related deaths were from interstitial pneumonitis; inadequate pulmonary function, multiple prior chemotherapy regimens, and prior chest irradiation all appeared to increase the transplant-related mortality. These results suggest a role for marrow transplantation in a subset of patients with relapsed Hodgkin's disease who are unlikely to be otherwise cured but are still responsive to conventional dose cytoreductive therapy. PMID- 2307992 TI - The American Society of Clinical Oncology and American Society of Hematology Recommended Criteria for the Performance of Bone Marrow Transplantation. AB - Both autologous and allogeneic bone marrow transplantation involve the management of severely immunosuppressed patients for extended periods of time. Both the extent and the duration of the immunosuppression and certain unique technical issues (eg, cryopreservation and the management of graft v host disease) require special preparation and commitment in any organization undertaking bone marrow transplantation. Participation in clinical trials is important. The following criteria are those minimally necessary for the safe and successful performance of the procedure. PMID- 2307991 TI - Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. AB - The purpose of this study was to determine which factors were associated with an increased risk of thrombo-hemorrhagic complications in a historical cohort of 100 consecutive and unselected patients with essential thrombocythemia (ET) in whom busulfan treatment was given when platelets were more than 1,000 x 10(9)/L and/or a major thrombotic or hemorrhagic event occurred. The incidence of major hemorrhagic complications was very low (0.33%/person-time at risk [pt-yr]) in comparison with that of thrombotic episodes (6.6%/pt-yr). In an adequate and appropriate control historical group of 200 patients, no severe hemorrhages were recorded and the incidence of thrombotic events was 1.2% pt-yr. Thus, the analysis of risk factors was restricted to this latter group of events. Age, a previous thrombotic event, and long duration of thrombocytosis were identified as major risk factors for thrombosis, while smoking, diabetes mellitus, hyperlipidemia, and hypertension did not influence the rate of thrombotic episodes. PMID- 2307994 TI - Energy agency examines radioisotope needs in preparation for the future. PMID- 2307993 TI - The missing era of breast cancer chemotherapy. PMID- 2307995 TI - Lines from the president. Alliance not reliance. PMID- 2307996 TI - Noninvasive assessment of coronary collaterals in man by PET perfusion imaging. AB - At present, coronary collateralization cannot be identified or assessed noninvasively in patients. In animal studies, coronary collaterals are associated with coronary steal, defined as a regional fall in perfusion during coronary arteriolar vasodilation. To determine the effect of coronary arteriolar vasodilation on collateral bed perfusion in man, myocardial perfusion imaging was performed before and after pharmacologic coronary vasodilation in patients with coronary artery disease (CAD). Regional myocardial activity of 82Rb or 13N ammonia was measured by positron emission tomography (PET) at rest and with intravenous dipyridamole/handgrip stress in 28 patients with angiographic collaterals and in 25 control patients with similar CAD severity by quantitative arteriography. Regional myocardial activity decreased after dipyridamole, indicating coronary steal, in 25 of 28 patients with angiographic collaterals and in only 4 of 25 control patients without angiographic collaterals. These findings suggest that developed collaterals are associated with myocardial steal in patients with CAD, allowing potential use of PET for non-invasive identification of coronary collateralization. PMID- 2307997 TI - The acetabulum: a prospective study of three-phase bone and indium white blood cell scintigraphy following porous-coated hip arthroplasty. AB - Although few studies address the use of three-phase bone scanning (TPBS) and indium-111-labeled white blood cell scintigraphy (111In-WBC) in hip arthroplasty utilizing a porous-coated prosthesis, the literature suggests that scintigraphic patterns in the uncomplicated patient may differ form that seen with the cemented prosthesis. In an attempt to determine the scintigraphic natural history, 25 uncomplicated porous-coated hip arthroplasties in 21 patients were prospectively studied with serial TPBS and 111In-WBC at approximately 7 days, and 3, 6, 12, 18, and 24 mo postoperatively. This report deals with findings related to the acetabulum. All 25 prostheses (144 of 144 scans) demonstrated increased uptake on the bone-phase images. Although this activity decreased with time, 76% had persistent uptake at 24 mo. Twenty-three of 25 prostheses (126 of 140 scans) showed increased uptake on 111In-WBC scintigraphy, invariably decreasing with time, but with 37% having significant uptake at 24 mo. Scintigraphic patterns in the uncomplicated porous-coated hip arthroplasty patient appear to differ from patterns described in cemented prostheses. PMID- 2307998 TI - Measurement of skin-to-kidney distance in children: implications for quantitative renography. AB - Variation in skin-to-kidney center distance has been shown to have a significant influence on quantification of renal function with the gamma camera. Several techniques to compensate for this variability have been proposed in adults, yet it has been suggested that depth correction is not necessary for quantitative renography in children. Skin-to-kidney center distances were measured from computed tomograms in 53 supine pediatric patients. Nearly 40% of the kidneys examined varied more than 1 cm from the average renal depth, and 8% deviated more than 2 cm. Right kidney depth differed from left kidney depth by more than 1 cm in less than 10% of the patients. Measurements were in agreement with regression equations based on lateral scintigraphy in children, but were consistently underestimated by nomograms developed for skin-to-kidney center distance in adults. Failure to recognize interindividual variability in skin-to-kidney center distance can introduce significant errors in quantitative pediatric renography. PMID- 2307999 TI - Utility of gallium imaging of the kidneys in diagnosing primary amyloid nephrotic syndrome. AB - We undertook a study to determine the value of gallium imaging of the kidneys in patients who had primary amyloidosis that was manifest clinically by nephrotic syndrome. We studied 28 patients with gallium-67 (67Ga) citrate scans performed 48 hr after injection. Intense (3+ to 4+) uptake was noted in both kidneys in 25 of 28 patients. Renal amyloidosis should be considered in the differential diagnosis when diffuse bilateral renal uptake of [67Ga]citrate is seen in the setting of nephrotic syndrome. Gallium uptake did not differentiate amyloid nephrotic syndrome from other causes of nephrotic syndrome. Renal gallium uptake showed a weak correlation with 24-hr urine protein excretion (p = 0.06). PMID- 2308000 TI - Single perfusion defect and pulmonary embolism: angiographic correlation. AB - One hundred and thirty-three ventilation-perfusion scans (V-P) with angiographic correlation were retrospectively reviewed to evaluate the frequency of pulmonary emboli (PE) in single perfusion defects (SPD), regardless of ventilation or radiographic findings. By angiography, 15 of 30 SPD cases had PE. Demographic data and clinical presentation were similar for PE and non-PE patients. However, 9 out of 15 patients with PE had recent surgery compared to none of the non-PE patients. SPD were seen in areas of ventilation and chest x-ray abnormalities in 12 of 15 PE and 11 of 19 non-PE cases. Size of the actual lesion was underestimated by scintigraphy in most cases. In 7 of 15 PE cases, the perfusion defect was larger than the corresponding ventilation abnormality. Most SPD were located at the bases. Twelve of 15 SPD in the PE group were at the posterior basilar segment. In the appropriate clinical setting, SPD carries at least a moderate probability for PE. When the clinical suspicion is high, a pulmonary angiography will be needed to confirm the diagnosis. PMID- 2308001 TI - Positron emission tomography of fluorine-18-deoxyglucose and image-guided phosphorus-31 magnetic resonance spectroscopy in brain tumors. AB - Positron emission tomography (PET) of 2(18F)-fluoro-2-deoxy-D-glucose (FDG) and volume-selective phosphorus-31 magnetic resonance spectroscopy (31P-MRS) are methods used to assess the energy metabolism of the brain. Both methods were studied with respect to their contribution to differential diagnosis in 23 patients with various brain tumors. The various neuroectodermal tumors differed with respect to their metabolic rate for glucose (MRGL). Benign and malignant tumors could be better differentiated by using tumor metabolism relative to contralateral brain and by evaluating heterogeneities in tumors. Low-grade gliomas usually showed normal 31P-MR spectra; high-grade gliomas were characterized by reduced and often split phosphodiester peaks and alkaline pH. Meningiomas, which had variable MRGL, typically showed extremely low phosphocreatine levels, reduced phosphodiesters, and alkaline pH. We concluded that FDG-PET and 31P-MRS examine different aspects of tumor metabolism. Therefore, both can contribute independently and complementarily to the differential diagnosis of brain tumors. PMID- 2308002 TI - In search of the hot appendix--a clinician's view of inflammation imaging. PMID- 2308003 TI - Osteoporosis in women with eating disorders: comparison of physical parameters, exercise, and menstrual status with SPA and DPA evaluation. AB - Osteoporosis has been reported in anorexia nervosa (AN), but not in other eating disorders. Thirty-three patients, 8 AN, 17 bulimia nervosa (BN), and 8 eating disorder not otherwise specified (EDNOS), were evaluated by bone densitometry (radius, spine, femur) to determine the prevalence and distribution of osteoporosis and the role of physical parameters, exercise and estrogen. All three diagnostic subgroups had evidence of decreased bone density, worst in the EDNOS subgroup and least in the BN subgroup. The most affected site was the femur, least the spine; the radius was intermediate. Age, body surface area, age of onset, and length of illness weakly correlated with the femur and spine density in the BN and EDNOS subgroups. Exercise was related to bone density in the AN subgroup in the femur, moderate exercise having a protective effect and strenuous exercise being detrimental. No significant correlation of bone density measurements with estradiol levels and/or history of amenorrhea was identified. Eating disorder patients are at risk for osteoporosis, which has multiple contributing factors including physical parameters and exercise. Estrogen deficiency by itself may not be a major causative factor. PMID- 2308004 TI - Tumor visualization with a radioiodinated phospholipid ether. AB - The known ability of phospholipid ethers to accumulate in certain tumors prompted the synthesis and evaluation of a radioiodinated phospholipid ether analog as a potential tumor imaging agent. Tissue distribution studies with [125I]-rac-1-0 [12-(m-iodophenyl)dodecyl-2-0-methylglycero-3- phosphocholine in rats bearing the Walker 256 carcinosarcoma showed the tumor to contain the highest concentration of radioactivity at 24 hr (15% of the dose) and a tumor-to-blood ratio of 13. Scintigraphic images taken at 24 hr compared favorably with those obtained with (67Ga)-citrate. In contrast with the latter, however, the phospholipid ether showed little propensity to accumulate in an inflammatory lesion in the rat. Tumor visualization was also accomplished in a rabbit bearing the V x 2 adenocarcinoma. We conclude that phospholipid ethers may represent a new class of carrier molecules for the transport of radionuclides to tumors. PMID- 2308005 TI - Utilization of labeled thymidine in DNA synthesis: studies for PET. AB - Carbon-111-thymidine and positron emission tomography (PET) have the potential for noninvasively measuring DNA synthesis in tumors and tissues. In order to validate this potential, one needs to construct accurate biochemical models that reflect the metabolism of thymidine, including its uptake and degradation as well as its incorporation into DNA. Our studies employed thymidine labeled in the methyl position using 11C, 14C, and 3H. Studies with rapidly proliferating tissues of mice demonstrated that most of the activity, 60 min after injection of labeled thymidine, was present in DNA, with smaller amounts found in metabolites. Studies in dogs, however, reveal that more activity was present in metabolites, rather than in the DNA of tumors and spleen tissue. HPLC analysis of canine blood after the injection of thymidine revealed rapid conversion of thymidine to thymine and other metabolites. We have found significant differences in the metabolism of [3H]thymidine versus thymidine labeled with radioactive carbon. These differences, which were not found when comparing 14C and 11C, indicate that [3H]thymidine is not an appropriate standard for comparison with PET studies employing [11C] thymidine. To accurately interpret images of [11C]thymidine as representations of DNA synthesis we are developing kinetic models that take into account the metabolism of thymidine and the contribution of degradation products to the 11C images. PMID- 2308006 TI - Indium-111-labeled LDL: a potential agent for imaging atherosclerotic disease and lipoprotein biodistribution. AB - Radiolabeling of low-density lipoprotein (LDL) and external imaging with a gamma camera would offer a means of taking advantage of the metabolic activity of developing atherosclerotic lesions in order to noninvasively detect and determine the extent of atherosclerotic cardiovascular disease. Indium-111-(111In) labeled LDL was prepared and its purity demonstrated by agarose electrophoresis and ultracentrifugation. In vitro studies with cultured human fibroblasts demonstrated significant inhibition of iodine-125-(125I) LDL binding to LDL receptors by 111In-LDL, although this was less than the inhibition produced by unlabeled LDL. Adrenal gland uptake of 111In-LDL by hypercholesterolemic rabbits was reduced by 86% compared to the level of uptake observed in normal rabbits. These results were compatible with downregulation of adrenal LDL receptors in the hypercholesterolemic rabbits. Uptake of 111In-LDL in the atherosclerotic proximal aorta of hypercholesterolemic rabbits was 2.5 times higher than in normal rabbits. These results suggest that 111In-LDL has the potential to be a useful agent for external imaging of atherosclerotic lesions and lipoprotein biodistribution. PMID- 2308007 TI - Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM. AB - Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.6 days) and 64Cu (t1/2 = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM2 continued to clear. Cu-PTSM and Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of [64Cu]-Cu PTSM. For comparison with the 64Cu brain image, a CBF (15O-labeled water) image (40 sec) was first obtained. Qualitatively, the H2(15)O and [64Cu]-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H2(15)O and 2.67 for Cu-PTSM. No redistribution of 64Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H2(15)O. This data suggests that [62Cu] Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET. PMID- 2308008 TI - Residual mass and negative gallium scintigraphy in treated lymphoma. AB - Two patients with treated lymphoma demonstrated a residual mass on CT following treatment. In both cases gallium-67 (67Ga) scintigraphy demonstrated increased uptake in the original tumor mass and no uptake in the mass after treatment. In both cases the entire residual tumor mass was resected and found to contain no cancer tissue. This is further evidence of the role 67Ga scintigraphy may play in monitoring response of lymphoma patients to treatment. In contrast, other imaging modalities such as ultrasound, plain film x-rays, or CT only show the presence of a mass but not its nature. PMID- 2308009 TI - Residual mass and negative gallium scintigraphy in treated lymphoma: when is the gallium scan really negative? PMID- 2308010 TI - Increased lung uptake on technetium-99m-sulfur colloid liver-spleen scans in patients with hepatic venoocclusive disease following bone marrow transplantation. AB - Three patients who developed signs and symptoms of liver dysfunction following autologous bone marrow transplantation showed varying degrees of increased lung uptake on technetium-99m-sulfur colloid (99mTc-SC) liver-spleen-scans and were subsequently demonstrated to have hepatic venoocclusive disease (VOD) at autopsy. Although increased lung uptake of labeled colloid has been noted in solid organ and bone marrow transplant patients, an association between this phenomenon and VOD has not been previously reported. PMID- 2308011 TI - Ocular melanoma: detection using iodine-123-iodoamphetamine and SPECT imaging. AB - Uptake of iodine-123-iodoamphetamine has been demonstrated in malignant melanoma using planar imaging techniques and has been used to detect an ocular melanoma at 12 hr postinjection. Using SPECT technique, an ocular melanoma is identified in a 64-yr-old male at 1 hr postinjection. PMID- 2308012 TI - MIRD Dose Estimate Report No. 14: radiation absorbed dose from technetium-99m labeled red blood cells. PMID- 2308013 TI - Human antimurine antibodies (HAMA) in vivo complex formation and the outcome of immunoscintigraphy. PMID- 2308014 TI - Splenic dynamics of indium-111-labeled platelets in idiopathic thrombocytopenic purpura (ITP) PMID- 2308015 TI - The effect of carrier on reaction rates. PMID- 2308017 TI - Another complication of intravenous catheterization: a case report. AB - The list of possible complications following central vein catheterization has been well described. A technique for placement of a catheter into a central vein has to be learned by the individual following guidelines dictated by anatomical understanding, literature reporting, and other practitioners' previous experience. We report here another complication of intravenous catheterization where the first catheter is severed completely by a second, larger needle. PMID- 2308016 TI - Uptake of trimethoprim and metronidazole in the seminal vesicle: experimental study. AB - A rat model for determining drug levels in the seminal vesicle was developed. In separate studies, trimethoprim and metronidazole were injected intravenously into rats and assays of seminal vesicle, plasma, and prostate performed. Drug levels were detected early in both the seminal vesicle and prostate. This appears to be the first study to report drug levels in the seminal vesicle. Metronidazole levels in the seminal vesicle were very low and short lived. PMID- 2308018 TI - On the epidemiology of child abuse. PMID- 2308019 TI - Treatment of venomous bite by high voltage direct current. AB - Between September 1988 and September 1989, 21 cases of confirmed or suspected spider bite were treated with high voltage direct current electric shock. In every case, tissue damage was arrested with the first treatment, and none of the cases required excision or graft. PMID- 2308020 TI - On cranberry juice. PMID- 2308021 TI - Methicillin-resistant Staphylococcus aureus: a descriptive analysis on veterans. AB - Concern over complications of a potentially large outbreak of methicillin resistant Staphylococcus aureus (MRSA) prompted intensive monitoring and establishment of effective communication lines between infection control practitioners, nurses, physicians, and microbiology personnel. From October, 1986, through September, 1987, 77 patients at the Veterans Administration Medical Center in Oklahoma City had MRSA. Charts were available for review on 63 of these patients. When those with charts available were reviewed, 41 patients had nosocomial (NC) and 22 had community-acquired (CA) MRSA. Of the 41 NC patients, 34 were infected (of which 17 died during hospitalization) and 7 colonized (3 died). Of the 22 CA patients, 15 were infected (4 died) and 7 colonized (2 died). Length of stay was NC-infected, mean 51.8 days; NC-colonized, 38.9 days; CA infected, 14.9 days; and CA-colonized, 16.1 days. This study shows the importance of NC MRSA, especially as it relates to hospital costs and care of many extended stay patients. PMID- 2308022 TI - Cocaine babies in Oklahoma. AB - Recreational use of cocaine has resulted in a dramatic increase in the incidence of fetal exposure to cocaine. Increased awareness by health professionals is needed to determine the extent of the problem in Oklahoma. PMID- 2308023 TI - Use of extracorporeal membrane oxygenation in the treatment of respiratory syncytial virus bronchiolitis: the national experience, 1983 to 1988. AB - In an effort to obtain data to provide the basis for the design of controlled clinical trials, we contacted all U.S. participants in the National ECMO Registry to assemble the national experience on the use of extracorporeal membrane oxygenation in respiratory syncytial virus bronchiolitis during the past 5 years. Twelve infants were treated at nine centers between 1983 and 1988. Eight had been born prematurely, and five had bronchopulmonary dysplasia. The mean age at onset of infection with respiratory syncytial virus was 108 +/- 102 days. The mean length of ventilator management before extracorporeal membrane oxygenation was 7.8 +/- 7.1 days. All infants had persistent hypoxemia with a mean arterial oxygen pressure of 39.2 +/- 11.7 torr (5.3 +/- 1.6 kPa) despite high ventilator pressures (mean airway pressure 19.7 +/- 6.4 cm H2O) and 100% inspired oxygen; six had air leak syndrome. Seven infants survived (58%). The mean duration of extracorporeal membrane oxygenation for survivors was 233 +/- 139 hours. Preexisting chronic lung disease did not predict a poor outcome: four of the five infants with bronchopulmonary dysplasia survived. Six of the survivors have subsequently achieved expected developmental milestones and one has slight motor delay. We conclude that, for infants with severe respiratory syncytial virus bronchiolitis whose condition deteriorates despite maximal ventilator management, extracorporeal membrane oxygenation may provide lifesaving support. The duration of successful treatment with this therapy may be longer than that for conventional neonatal indications, but excellent neurologic outcome may be expected in survivors. PMID- 2308024 TI - Value of the postmortem examination in a pediatric population with leukemia. AB - Because of concerns about the declining autopsy rate, an attempt was made to evaluate the contributions from the postmortem examination in a pediatric population with leukemia. Accordingly, 161 autopsies performed between 1970 and 1985 were reviewed and the diagnoses compared with those listed in the clinical records of the same patients. New diagnoses were grouped into diagnoses of diseases thought to have contributed to the death of the patient, those of diseases thought to have contributed to the morbidity of the patient, those of presumed toxic reactions to drug therapy, and diagnoses of academic interest. The newly diagnosed diseases thought to have contributed to the patient's death either had been totally unsuspected by the clinician or had been suspected but incorrectly diagnosed. The most common revelation was the identification of mycotic infections that were thought by the clinician to have been bacterial in origin. The clinical diagnosis of these kinds of infections progressively improved during the study period. Because the changes in diagnoses and therapy, particularly the increasing use of antimycotic therapy, could be directly attributed to autopsy findings and, more recently, because of the expanding use of more toxic multiagent chemotherapy, we believe that the postmortem examination remains an important procedure, even in clinical situations where much is known about the patient. PMID- 2308025 TI - A comparative study of virus isolation, polymerase chain reaction, and antigen detection in children of mothers infected with human immunodeficiency virus. AB - We report on an investigation designed to compare the polymerase chain reaction (PCR) with culture and p24 measurement for the diagnosis of human immunodeficiency virus (HIV) infection in infants and children. Forty-five children born of mothers with antibodies to HIV type 1 were studied; P24 antigen was measured in plasma, and HIV-1 proviral DNA was sought in peripheral blood mononuclear cells after amplification by PCR. In 26 cases, blood specimens were cultured for HIV; in all but two instances cultures were established at the same time that the PCR test was performed. Primer pairs in three regions of the proviral genome were used for the PCR test. There was good agreement between the results obtained from PCR tests and from cultures; of 24 children in whom both tests were done at the same time, 10 had positive results on both the culture and the PCR test, 1 had positive results on the PCR test but negative culture results, and 13 had negative results on both tests (concordance 96%). Measurement of p24 antigen in plasma was, in contrast, an insensitive marker of infection: 6 of 12 infants with positive cultures had positive p24 test results, and 8 of 18 infants had positive PCR test results. Sixteen children with subsequent seronegativity for HIV-1 had negative PCR results. This study provides further evidence that the PCR test is a valid alternative to viral culture for the diagnosis of pediatric HIV infection. PMID- 2308026 TI - Chronic mucocutaneous candidiasis in childhood and complications of non-Candida infection: a report of the Pediatric Immunodeficiency Collaborative Study Group. AB - We reviewed the clinical course in 43 patients from eight medical centers who were given the diagnosis of chronic mucocutaneous candidiasis, a rare disorder of unknown cause that may occur in childhood. Recurrent or severe infections with organisms other than Candida were seen in 80% of the patients. There were nine cases of septicemia. Seven patients have died; six of these deaths were directly related to non-Candida infectious complications. Endocrine dysfunction, including Addison disease (11 patients) and hypothyroidism (9 patients), was seen in 19 of 43 patients. Immunologic studies failed to reveal a consistent abnormality, although two of five patients with reversed T4/T8 ratios are among those who have died. Ketoconazole was effective in controlling symptoms of candidiasis in most patients. The findings from this study indicate that non-Candida infections cause serious morbidity and may result in death in patients with chronic mucocutaneous candidiasis. PMID- 2308027 TI - Fetal brain disruption sequence. AB - The fetal brain disruption sequence is a recognizable pattern of defects that includes moderate to profound microcephaly, overlapping sutures, occipital bone prominence, and scalp rugae. The condition is postulated to arise from partial brain disruption during the second or third trimester with subsequent fetal skull collapse resulting from decreased intracranial hydrostatic pressure. Proposed causes include prenatal viral or parasitic infections and vascular disruptions. We report seven infants with the fetal brain disruption sequence. Two of these patients died. A changing phenotype with time was seen in three. Recognition of this phenotype is critical because the condition has a uniformly poor prognosis for infants but the recurrence risk in future pregnancies is low. PMID- 2308028 TI - 3-Hydroxydicarboxylic aciduria--a fatty acid oxidation defect with severe prognosis. AB - We describe five patients with a suspected defect in the beta-oxidation of fatty acids characterized by a massive excretion of 3-hydroxydicarboxylic acids in the urine and accumulation of 3-hydroxy fatty acids in serum during acute illness. Long-chain and medium-chain acyl-coenzyme A dehydrogenases in fibroblasts were normal in all patients. Four of them died of cardiomyopathy and liver insufficiency at 3 to 14 months of age. Two of the patients had elder siblings who had died unexpectedly in early infancy. These patients differ from previously described patients with beta-oxidation defects. PMID- 2308029 TI - Pediatric applications of extracorporeal membrane oxygenation. PMID- 2308030 TI - The disappearing autopsy. PMID- 2308031 TI - Slipped capital femoral epiphysis during treatment with recombinant growth hormone for isolated, partial growth hormone deficiency. PMID- 2308032 TI - Localized tracheomalacia or bronchomalacia in children with intractable cough. PMID- 2308033 TI - Hormone-producing ganglioneuroblastoma simulating intestinal pseudoobstruction. PMID- 2308034 TI - Intellectual and functional status at school entry of children who weighed 1000 grams or less at birth: a regional perspective of births in the 1980s. AB - The intellectual and functional status of a regional cohort of children who weighed 501 to 1000 gm when born between 1980 and 1982 was evaluated at a mean age of 5 1/2 years by standard psychometric tests. Of 90 long-term survivors (survival rate 49%), 78 children (87%) had the full test battery, 5 children (6%) had other tests (4 were blind), and one child was untestable. Most of the mean scores were within 1 SD of the test norms; the lowest scores were in the McCarthy Motor scale and in the Beery Test of Visual-Motor Integration. Children without neurologic impairments and those with an IQ greater than or equal to 68 (n = 60) had higher overall scores but still performed poorly on the Motor subscale and the Beery test. Children who weighed less than 800 gm at birth (n = 28) were similar to those who weighed greater than 800 gm (n = 50), except in the Memory and Motor subscales, in which they performed significantly less well. At a functional level, determined by the Vineland Adaptive Behaviour Scales, two thirds of the children were performing in the adequate range and the remainder in the moderately low to low range. Of the 43 children with no neurosensory impairments and an IQ greater than or equal to 84, 49% were identified (by the Florida Kindergarten Screening Battery) to be at mild to high risk for future learning disabilities. The data from this unselected population provide an unbiased estimate of the prevalence of intellectual and functional problems in children who weighed less than or equal to 1000 gm at birth. PMID- 2308035 TI - Vitamin D and mineral metabolism in the very low birth weight infant receiving 400 IU of vitamin D. AB - STUDY OBJECTIVE: To examine (1) the effect of vitamin D intake (380 to 480 IU daily) on plasma 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25 (OH)2D) concentrations and (2) the relationship of 1,25-(OH)2D to calcium and phosphorus absorption and retention in the very low birth weight infant receiving a preterm infant formula. SUBJECTS: Eleven "well" infants with a birth weight and gestational age (mean +/- SD) of 1078 +/- 128 gm and 29 +/- 1.9 weeks, respectively, were studied for a 3-week period. Weight and postnatal age (mean +/ SD) at the beginning of the study were 1132 +/- 56 gm and 16 +/- 6 days, respectively. All infants were fed a preterm infant formula and tolerated a full enteral intake (120 kcal/kg/day) for the duration of the study. INTERVENTIONS: Plasma 25-OHD and 1,25-(OH)2D concentrations were measured at the beginning of the study and at the beginning of each 48-hour balance period. Calcium and phosphorus balance studies (n = 33) were performed weekly. MAIN RESULTS: Plasma 25-OHD (30 +/- 10 ng/ml) and 1,25-(OH)2D (54 +/- 14 pg/ml) concentrations were normal at the beginning of the study. Plasma 25-OHD values did not change, but 1,25-(OH)2D values increased (p less than 0.001) throughout the study. Plasma 1,25-(OH)2D concentrations were not related to calcium or phosphorus absorption and retention, but were a linear function of postconceptional age. CONCLUSIONS: Normal vitamin D status and activity are maintained in the very low birth weight infant fed a high calcium formula (380 to 480 IU of vitamin D daily). Plasma 1,25 (OH)2D concentrations are not related to calcium absorption but are linearly related to maturity. PMID- 2308036 TI - Longitudinal evaluation of polymorphonuclear leukocyte chemiluminescence in premature infants. AB - A chemiluminescence (CL) microassay was used to evaluate polymorphonuclear leukocyte (PMN) function in premature newborn infants longitudinally during a 2 month period and in healthy adult control subjects. At postnatal ages of 12, 26, 40 and 54 days the infants' mean peak CL activity was significantly lower than that of the adults. Infants with one or more low CL responses were more severely ill than those with normal CL activity. The infants with low CL responses had longer hospital stays and a higher frequency of serious infections, as well as more days of level 3 care, antimicrobial therapy, supplemental oxygen, assisted ventilation, and total parenteral nutrition. The PMN CL activity before, during, and after episodes of serious infection did not differ. In addition, a high frequency of depressed CL activity was observed at the time of infection. Our findings are consistent with previous studies suggesting that defective PMN oxidative metabolic responses are more common in neonates undergoing stress. Our results further suggest that defective PMN function may persist for the first 2 months of life and during the course of serious infection. Enhancement of PMN host defense may be an important strategy in the management of neonatal sepsis. PMID- 2308037 TI - Surfactant protein A concentrations in tracheal aspirate fluid from infants requiring extracorporeal membrane oxygenation. AB - To understand the lung abnormalities leading to respiratory failure in infants, we measured 35,000-dalton surfactant protein A concentrations in tracheal aspirate fluid collected daily from 25 infants receiving extracorporeal membrane oxygenation (ECMO). Surfactant protein A concentrations were standardized per milligrams of total protein present in the aspirate. Among the 23 survivors with complete data, the surfactant protein A concentration increased significantly with time (p less than 0.0001). Concurrent increases in lung compliance (p less than 0.0001) and radiographic scores (p less than 0.0001) were also observed. This increase in surfactant protein A content may reflect lung recovery from barotrauma and oxygen toxic effects or be a response to the primary pulmonary disease process. The two infants who did not survive extracorporeal membrane oxygenation failed to demonstrate these trends. PMID- 2308038 TI - Leukopenia associated with extracorporeal membrane oxygenation in newborn infants. PMID- 2308039 TI - Prenatal diagnosis of nonketotic hyperglycinemia: enzymatic analysis of the glycine cleavage system in chorionic villi. PMID- 2308040 TI - Effects of lactose intake on nutritional status in premature infants. PMID- 2308041 TI - Computer-assisted detection and intervention in adolescent high-risk health behaviors. AB - Because adolescents avoid bringing sensitive issues, such as substance abuse, suicide, and sexual activity, to pediatricians, and may fail to realize that they need health education or services, a computer program was designed to facilitate reporting of high-risk psychosocial and health behaviors and to provide specific health advice and referral for timely professional intervention. Computer printouts done anonymously by a random sample of 265 adolescents after a physical examination were compared with those of a matched group of 294 who were predirected to share the printout with the clinician at their examinations. The former elicited more positive responses to sensitive health problems, but both computer groups responded significantly more often about most high-risk issues than a matched written questionnaire group of 251. Almost all adolescents said that they reported true information to the computer and read all the information it printed. Experience with 3327 teenagers demonstrated that 89% preferred the computer over a questionnaire or personal interview, but nearly all were willing to share the printout with the pediatrician, which should facilitate clinical evaluation. The nonjudgmental computer can identify problem areas and deliver automated medical advice and referral. Automated health assessment and education may become a useful adjunct for addressing adolescent health issues. PMID- 2308043 TI - Regulation of working hours for pediatric residents. PMID- 2308042 TI - Adolescent contraceptive behavior: an assessment of decision processes. AB - The utility of a rational model of contraceptive use in adolescents was evaluated in a cohort of 325 sexually active adolescents aged 14 to 19 years. Adolescents were interviewed regarding their beliefs about the consequences of using each of four methods of contraception, evaluation of those consequences, perception of the wishes of others regarding use of each method, motivation to comply with those wishes, general attitude toward using the method, view of general social expectations regarding their use of the method, and their intention to use the method during the next year. They were reinterviewed 1 year later to determine actual use. The results support the utility of this model for understanding adolescent behavior. Significant associations were found between intentions to use contraceptive methods and their actual use. Intentions were significantly related to adolescents' attitudes toward using the methods and their perception of social expectations regarding use. General attitudes were significantly related to a summary score reflecting the adolescents' beliefs about specific consequences of use weighted by their evaluations of them. General social perceptions were significantly related to a summary score of perceived desires of specific individuals multiplied by the adolescent's desire to comply with those desires. These findings indicate that physicians can be more effective in clinical practice by querying adolescents about their beliefs and intentions and about their perceptions of significant individuals in their lives. PMID- 2308045 TI - Ceftriaxone versus cefuroxime for treatment of bacterial meningitis. PMID- 2308044 TI - Cefuroxime versus ceftriaxone for bacterial meningitis. PMID- 2308046 TI - Carrier state in pertussis. PMID- 2308047 TI - Scrotal hair in infant with empty sella turcica. PMID- 2308049 TI - Histologic appearance of varioliform gastritis. PMID- 2308048 TI - Serum triglyceride concentrations in infants with bronchopulmonary dysplasia. PMID- 2308050 TI - Phase separation modulation and aggregation prevention: mechanism of the non solvent addition method in the presence and absence of polyisobutylene as an additive. AB - The mechanism by which microcapsule aggregation is diminished in the presence of low concentrations of adjunct non-walling polymers such as polyisobutylene (PIB) in organic solvents is uncertain. It is here investigated by phase separation studies employing the non-solvent addition method (cyclohexane) in parallel with microencapsulation experiments, using Eudragit wall polymers and tetrahydrofurane (THF) as solvent with and without PIB. Polymer incompatibility leads to formation of two dilute liquid phases and emulsification from the outset. Progressive solvent transfer to the PIB phase modulates the rate of wall polymer desolvation and maintains the concentrated wall polymer phase in a fluid state during the critical microencapsulation stages of wall polymer entrapment--and spreading. A three-phase system is formed when gelling ensues (L1 + L2 + gel). In the absence of PIB, phase separation leads immediately to deposition of the wall polymer in gel form (L1 + gel) leading to adhesion. Phase diagrams are presented. PMID- 2308051 TI - High performance liquid chromatographic analysis of liposome stability. AB - Two techniques have been studied for their suitability for the analysis of the stability of liposomes: (1) High Performance Gel Permeation Liquid Chromatography (HPGPLC), a TSK G5000PW Ultrogel column; (2) Gel Permeation Chromatography (GPC), a Sepharose 4B column. The stability of dual radio-labelled, cholesterol-poor and cholesterol-rich, negatively charged liposomes in vitro (in saline and in serum), and in vivo, have been investigated using these two techniques. The HPGPLC TSK G5000PW column proved to be the superior technique for the analysis of liposome stability with the advantages of rapid run times, increased sample recovery, and smaller sample volumes were required. The results obtained confirm that inclusion of a high ratio of cholesterol into the liposome structure prevents phospholipid loss when exposed to serum, and that the cholesterol-poor liposome structure is dramatically altered under the same conditions. In conclusion, the TSK G5000PW column is ideal for monitoring movement of phospholipid between liposomes and serum proteins and for detecting changes in liposome size. PMID- 2308052 TI - Microencapsulation using poly (L-lactic acid) II: Preparative variables affecting microcapsule properties. AB - Poly (L-lactic acid) [L-PLA] microcapsules containing phenobarbitone were prepared from a w/o emulsion system, using light liquid paraffin as the continuum and a solution of phenobarbitone and L-PLA in acetonitrile as the disperse phase. Increasing stirring rate and emulsifying agent concentration were found to reduce microcapsule size. Spans (sorbitan esters of fatty acids) and Brijs (polyoxy ethylene ethers of fatty acids) with different physicochemical properties have been found to produce microcapsules of differing size. An attempt has been made to correlate emulsifier properties and the corresponding microcapsule size. It was found that the emulsifiers had little or no effect on the interfacial tension between light liquid paraffin and acetonitrile and there was no correlation between HLB of the emulsifiers and the resulting microcapsule size. It was postulated that microcapsule size would be affected by the packing of the emulsifier at the interface which would depend on the structure of the emulsifier. Closer, more uniform packing by the straight chain saturated fatty acid containing emulsifiers produced smaller microcapsules than when lose packing, which existed when emulsifiers containing either three fatty acid chains or a 'V' shaped cis-double bond containing fatty acid chain, were used. Microcapsule size was found to increase rapidly with an increase in polymer concentration, if this polymer concentration was increased in conjunction with an increase in the total solid content of the dispersed phase. Increases in polymer concentration by reducing the quantity of solvent for the dispersed phase caused little increase in mean microcapsule size. The phenobarbitone content in the microcapsules was not affected significantly by variations in the preparative parameters. PMID- 2308053 TI - Microencapsulation using poly (L-lactic acid) III: Effect of polymer molecular weight on the microcapsule properties. AB - Poly (L-lactic acid) microcapsules were prepared using an emulsification and organic solvent evaporation technique (w/o system) with phenobarbitone as a reference core. Three polymers of different molecular weight (61,300; 43,200, 2400), were used to prepare different core loaded microcapsules. Microcapsule size increased with increase in polymer molecular weight. Microcapsule size was also found to increase with increase in core loading with the two high molecular weight polymers, whilst the low molecular weight polymer tended to aggregate to form larger microcapsules than expected. The calculated microcapsule density was found to decrease with an increase in the polymer molecular weight and core loading. 'Encapsulation efficiency' was reduced with the decrease in initial theoretical core loading. However, the phenobarbitone content of the microcapsules was not affected by the difference in polymer molecular weight. Significant morphological differences were observed due to variations in the polymer molecular weight. The two high molecular weight polymers were found to produce non-uniform, porous microcapsules, whilst low molecular weight polymer formed a uniform non-porous surface when core loading was low. With increasing core loading, an increasing number of phenobarbitone crystals were observed on the surface and microcapsules became increasingly porous. This was more evident after release of the drug. Differential scanning calorimetry of the microcapsules showed thermal events for both the polymer and phenobarbitone. PMID- 2308054 TI - Microencapsulation using poly(L-lactic acid) IV: Release properties of microcapsules containing phenobarbitone. AB - Microcapsules containing phenobarbitone were prepared from poly(L-lactic acid), using a water/oil emulsification and evaporation process. Polymers of three different molecular weights were used. Particle size was found to increase with an increase in core loading and polymer molecular weight. Release studies were carried out at buffer pHs of 2 and 9 at 37 degrees C. The release mechanism was found to follow a square root of time relationship. Almost 90 per cent of the phenobarbitone was released within 2 h. The release rate was not a direct relationship with the phenobarbitone content of the microcapsules because of the differing size and surface area of the microcapsules. However, normalized release rates (release rate/specific surface area) were found to increase linearly with the increase in phenobarbitone content. First order release plots of the data were not found consistent with the core loading. The release at a buffer pH of 9 was very rapid and with some microcapsules was faster than solution of the uncoated crystalline phenobarbitone. At pH 2 release was also very rapid, due to the presence of large pores in the microcapsules of high molecular weight polymers. Release from the microcapsules prepared from low molecular weight polymer was slower than those from high molecular weight polymers. Microcapsules from the low molecular weight polymer were found to swell in the dissolution medium and finally disintegrated into smaller fragments. PMID- 2308055 TI - Freeze substitution technique for identifying liposomes incorporated in emulsion and gel preparations. AB - The freeze-substitution technique was utilized for identifying unilamellar and multilamellar liposomes incorporated in gel or emulsion preparations. Samples of each preparation were rapidly frozen in liquid propane and the ice formed in the process was substituted with acetone containing 2 per cent osmium tetroxide at 70 degrees C. Electron micrographs obtained by both freeze-fracture and freeze substitution methods showed the presence of either small unilamellar or multilamellar vesicles in all the liposome preparations. Results clearly demonstrated that freeze-substitution is a simple and cost-effective technique in comparison to the traditional freeze-fracture method and can be successfully used to characterize liposomes incorporated in dermatological or cosmetic vehicles. PMID- 2308056 TI - Targeted delivery of low dose doxorubicin hydrochloride administered via magnetic albumin microspheres in rats. AB - The efficacy of magnetic albumin microspheres in the targeted delivery of an anti cancer agent, doxorubicin hydrochloride, has been investigated in rats. Using the tail as a target organ, the animals were intra-arterially administered with either 0.12 mg/kg of free drug, or 0.04 mg/kg of microsphere entrapped drug in the presence of a 8000 Gauss magnet applied for 30 min at the target-site. In each group, the animals were sacrificed over a 48 h period and their various tissues analysed for drug concentration using HPLC. It was found that compared to the free drug, a one-third dose of microsphere entrapped drug resulted in almost eight times higher drug exposure (AUC0-infinity) at the target site. In addition, the drug delivery to all the non-target tissues, including liver and heart, was substantially reduced. The study confirms the efficacy of magnetic albumin microspheres in the targeted delivery of chemotherapeutic agents. PMID- 2308057 TI - Pharmacokinetics of small unilamellar liposomes and incorporated lonazolac after i.m. administration. AB - The nonsteroidal anti-inflammatory drug lonazolac [3-(p-chlorophenyl)-1 phenylpyrazole-4]-acetic acid was incorporated into the bilayer of liposomes. The unilamellar and homogeneously sized liposomes with a diameter of 45 +/- 7 nm were prepared by controlled detergent dialysis. The maximal amount of lonazolac incorporation is 0.140 mg per mg egg phosphatidylcholine (egg PC). The liposomes were stable over a year. Pharmacokinetics of the 3H- and 14C-labelled liposomes and of the 14C-labelled lonazolac was investigated after i.v. and i.m. administration to rabbits. The i.m. injected liposomes showed a terminal half life of 74 h and after 24 h 7 per cent of the administered lecithin was still in the plasma. Eight hours following the i.m. injection of the liposomes, the plasma levels of lonazolac were significantly higher compared to the reference. A portion of the liposomes was released from the muscle into the circulation. A great share of lonazolac was quickly interchanged between the liposomes and the surrounding tissue. In additional experiments small oligolamellar liposomes should be used to decrease the interchange of lonazolac and to enhance the plasma levels of liposomal incorporated lonazolac. PMID- 2308059 TI - Understanding family response to childhood chronic conditions. PMID- 2308058 TI - Management behaviors: day-to-day adjustments to childhood chronic conditions. AB - To understand how families who have children with chronic conditions make daily adjustments to accommodate the children's special needs, the concept of management behaviors is explored. On a theoretical level, the adjustments are linked to an emerging conceptual model, family management style (FMS). As such, the management behaviors component of the FMS model is highlighted and developed to guide further clinical exploration and research. PMID- 2308060 TI - Family management style in juvenile diabetes: a case illustration. AB - A case analysis of a family's experience with juvenile diabetes is used to illustrate the three interactive components of the family management style (FMS) model proposed by Knafl and Deatrick. Family members' definition of the situation, management behaviors, and their sociocultural context are described and related. A shared family management style was derived from these descriptions and relationships. PMID- 2308061 TI - Interactional styles of parents following the birth of a high-risk infant. AB - Using the concept of family management style (FMS) proposed by Knafl & Deatrick (1990), this article illustrates three configurations of defining and managing styles used by dyads in response to the birth of a high-risk infant. The analysis includes a discussion of the applicability of the framework to an acute illness situation. PMID- 2308062 TI - Family management style: concept analysis and development. AB - Consistent with nursing's ongoing emphasis on theory development is the recognition of concept analysis's contribution to the advancement of theory. Following Sartori's framework for concept analysis, the authors analyzed the concept family management styles (FMS) as it relates to families in which there is a chronically ill or disabled child. The analysis includes both a review of existing conceptualizations of FMS and a model for reconceptualizing the concept. The systematic conceptualization of family response to chronic illness provides an essential foundation for developing effective, sensitive interventions that promote the growth of individual family members and the family unit as a whole. PMID- 2308063 TI - Using interpretive methods to understand family caregiving when a child is blind. AB - Interpretive research methods can enhance nursing practice with families caring for a child with a chronic illness or handicapping condition by providing an understanding of the family caregiving experience based on an interpretation of the meanings, practices and concerns of family caregivers themselves. In this article, the authors give an introductory overview to interpretive research and a discussion of its contributions to family nursing, using an illustration taken from an interpretive study of the family experience of caring for a blind child. PMID- 2308065 TI - Forgiveness. PMID- 2308064 TI - Creative strategies for pediatric nursing research: data collection. AB - As the researcher contemplates the design and methodology of a study involving children, the age and maturity of the child are key factors for consideration. A good understanding of the child's cognitive and developmental level of functioning will greatly facilitate the explanation to the child and the process of obtaining data from the child. The successful outcome of a study may depend on how well the investigator uses this knowledge and is able to make appropriate adaptations in data collection to meet the requirements of the study design. PMID- 2308066 TI - The federal government and child health. PMID- 2308067 TI - Nonshared environmental influences and personality differences in adult twins. AB - The twin design was used to examine the importance of different experiences of siblings within the family and to identify relations between twins' personality differences and their differential experiences. A sample of 161 monozygotic and 74 dizygotic twin individuals between the ages of 18 and 75 years retrospectively reported on their different experiences when growing up. The Sibling Inventory of Differential Experience (SIDE) was used for the first time with a sample of twin siblings. In addition, the twins provided self-report measures of affect and personality. In contrast to results from a sibling adoption design, this study of twins showed greater evidence for genetic variance in the SIDE scales. Nevertheless, the SIDE showed significant associations with differences in personality and affect for monozygotic twins, which reflect pure environment behavior relations. PMID- 2308069 TI - Self-esteem and perceptions of conveyed impressions: is negative affectivity associated with greater realism? AB - Two studies examined the notion that negative affectivity (Watson & Clark, 1984) is associated with more accurate perceptions of conveyed impressions in social interactions. In Study 1 (n = 160), low self-esteem (LSE) and high self-esteem (HSE) subjects were paired with either an LSE or an HSE partner. After a 15-min interaction, they rated themselves, their partners, and how they believed their partners would rate them on 20 adjectives related to social competence. Study 2 (n = 40) was identical except that each interaction was observed by 2 observers who rated each participant, and participants also rated how they believed an observer would rate them. LSE subjects exhibited greater accuracy only with respect to the elevation component of observers' ratings; HSE subjects overestimated the positivity of observers' evaluations, whereas LSE subjects were relatively accurate. However, LSE subjects exhibited less overall accuracy with respect to their partners' ratings. We argue that when these results are considered with earlier research, there is no support for the notion of depressive realism in assessing conveyed impressions. PMID- 2308068 TI - Psychoticism as a dimension of personality: a multivariate genetic test of Eysenck and Eysenck's psychoticism construct. AB - In this study, we applied multivariate genetic analysis, a generalization of factor analysis and behavior genetic analysis, to responses to items of the Psychoticism scale of the Eysenck Personality Questionnaire by 2,903 adult same sex Australian twin pairs. Item loadings on genetic, shared environmental, and nonshared environmental common and specific factors were estimated. The genetic factor structure differed considerably from the environmental structures, particularly in men. The genetic correlation between suspiciousness items and items reflecting unconventional or tough-minded attitudes or hostility to others was negative, but the environmental correlation was positive. Thus, conventional behavior genetic studies that have reported significant heritability of psychoticism, on the basis of analyses of scale scores, are misleading as to what trait is being inherited. PMID- 2308070 TI - Stereotypic and nonstereotypic sex role trait and behavior orientations, gender identity, and psychological adjustment. AB - This study examines the relations among sex role trait and behavior orientations, gender identity, and psychological adjustment in order to test traditional and contemporary perspectives regarding the adjustment implications of stereotypic and nonstereotypic sex role trait and behavior orientations. Measures of sex role personality traits and behaviors and scales assessing depression, anxiety, and social maladjustment were administered to 235 college men and women. In addition, subjects completed measures of gender identity and gender adequacy. Contrary to traditional perspectives, androgynous men and women and cross-sex-typed women were no less well adjusted than sex-typed individuals. However, consistent with traditional perspectives, men who were low in masculine characteristics (and men and women low in both masculine and feminine characteristics) did appear less well adjusted on measures of depression, anxiety, and social maladjustment. Furthermore, low masculinity men had less secure gender identities. No such gender identity disturbances were found in women. PMID- 2308071 TI - Self-other differences in children's perceptions about the causes of important events. AB - Three studies examined differences between children's (ages 8-15) beliefs about the effectiveness of multiple internal and external causes for producing outcomes in their own lives versus in those of their peers. Differences specific to the school domain were found: Starting at age 11 or 12, children perceived internal causes as more important for others than for themselves; and only beliefs about the self related to perceived control. More strikingly, a sample of gifted children, who presumably receive social feedback that they are different from their peers, reported that (a) they exerted more control and possessed more ability than their peers and (b) other children knew less about the causes of school performance and had to rely more on effort and powerful others; only beliefs about the self correlated to cognitive performance. These results suggest that self-other differences are produced by both developmental change and environmental opportunities. PMID- 2308072 TI - Role of cognitive-emotional mediators and individual differences in the effects of media violence on aggression. AB - Two experiments were conducted to test the hypothesis that observation of media violence elicits thoughts and emotional responses related to aggression. In Experiment 1, highly violent videotapes elicited more aggressive cognitions than did a less violent tape. This effect was moderated by the trait of stimulus screening. In Experiment 2, aggressive cognitions increased with the level of violence in the videotape, and physical assaultiveness influenced this effect. Hostility and systolic blood pressure were higher in response to the most violent video than in response to the other two. Hostility was influenced by emotional susceptibility and dissipation-rumination, and systolic blood pressure was influenced by emotional susceptibility and assaultiveness. PMID- 2308073 TI - Individual differences in entrainment of mood to the weekly calendar. AB - This study addressed two questions: Do daily fluctuations in mood exhibit a 7-day (circaseptum) cycle, and are there reliable individual differences in how entrained people's moods are to such a weekly cycle? Spectral analysis of daily mood over 84 occasions revealed a strong weekly rhythm in the temporal organization of mood in a sample of 74 undergraduates. A sine wave with a period of 7 days accounted for 40% of the variance in the daily mood data. Individual differences were also found in how entrained subjects' moods were to this weekly rhythm. We predicted that extraverts (compared with introverts) should be less entrained to a weekly cycle. Results suggest that the novelty- and sensation seeking behavior of extraverts most likely serves to lessen the cyclical predictability of their day-to-day moods. The origin and psychological meaning of the 7-day week are discussed. PMID- 2308074 TI - Perceptions of social responsibilities in India and in the United States: moral imperatives or personal decisions? AB - Indian and American adults' and children's (N = 400) moral reasoning about hypothetical situations in which an agent failed to help someone experiencing either life-threatening, moderately serious, or minor need was compared. For 1/3 of Ss, the agent's relationship to the needy other was portrayed as that of parent; for another 1/3, as that of best friend; for the rest, as that of stranger. Indians tended to regard the failure to aid another in moral terms in all conditions. In contrast, Americans tended to view it in moral terms only in life-threatening cases or in cases of parents responding to the moderately serious needs of their children. The results imply that Indian culture forwards a broader and more stringent view of social responsibilities than does American culture. Discussion centers on theoretical implications of the various cultural, need, role, and developmental effects observed. PMID- 2308075 TI - Victims' perceptions of social support: what is helpful from whom? AB - Although research has demonstrated that social interactions influence psychological well-being, little is known about what specific actions victims of stressful life events experience as helpful or unhelpful. Wortman and Dunkel Schetter (1979) previously suggested that victims frequently experience rejection, withdrawal, and communication problems with those close to them. To address these issues, 55 cancer patients were interviewed concerning the specific actions they found to be helpful or unhelpful from several potential support providers: spouse, other family members, friends, acquaintances, others with cancer, physicians, and nurses. The data indicated that the Wortman and Dunkel Schetter victimization model applied better to interactions with friends and acquaintances than to interactions with close family members. In addition, support was found to be partially dependent on the source: Particular actions were perceived to be helpful from some but not other network members. Implications for theory and research on social support are discussed. PMID- 2308076 TI - Functional and dysfunctional impulsivity: personality and cognitive correlates. AB - The 3 studies reported here were designed to clarify the nature of the personality trait of impulsivity. Two types of impulsivity were distinguished. Dysfunctional impulsivity is the tendency to act with less forethought than most people of equal ability when this tendency is a source of difficulty; most previous work on impulsivity appears to have focused on this trait. Functional impulsivity, in contrast, is the tendency to act with relatively little forethought when such a style is optimal. The present work indicates that these two tendencies are not highly correlated and that they bear different relations both to other personality traits and to the manner in which certain basic cognitive processes are executed. PMID- 2308077 TI - The perioperative experience of cesarean birth: preparation, considerations, and complications. PMID- 2308078 TI - Challenges of the obstetric operating room: trials and trends in management and programs. PMID- 2308079 TI - Transport of the surgical neonate. PMID- 2308080 TI - The infant with cleft lip or palate: more than a surgical problem. AB - In summary, children with cleft lip or palate require multidisciplinary, long term care that presents a challenge for the child, family, and health care providers. Helping the patient achieve satisfactory function, appearance, and sense of well-being by his or her young adulthood is a realistic goal for these individuals. PMID- 2308081 TI - Kinematics of sport wheelchair propulsion. AB - Eight international caliber wheelchair male athletes (3 basketball, 5 distance track) performed an all-out propulsion effort from a standing start for 10 seconds on a wheelchair ergometer. Comparisons between the basketball and track athletes on linear wheelchair and push rim velocity during the first 3 pushes and the peak value indicated that the basketball players had a significantly (p less than .05) higher push rim velocity throughout the effort and a higher wheelchair velocity only at the end of the first push. The track athletes attained a significantly higher peak wheelchair velocity. Graphical comparison of the best individual basketball and track athletes' performances indicated that the track athletes caught up to the basketball players after about 3.7 seconds or 12 meters and travelled 49 meters in the 10 seconds, compared to 37 meters for the basketball players. Differences in push rim and wheel diameter are considered the major factor in the noted differences in propulsion kinematics of basketball and track wheelchairs. PMID- 2308082 TI - Preventing occupied wheelchairs from falling down stairs. AB - The hypothesis was tested that wheelchairs could be prevented from accidentally falling down stairs. A rigid post was attached to the wheelchair frame immediately behind the caster (clearance of 13 mm) such that it would strike the floor just after the casters dropped off an edge. The device was tested by means of a 3-degree ramp at the lower end of which was a level surface that ended with a 11-cm vertical drop. Twenty able-bodied subjects descended the ramp, by gravity alone, from progressively greater distances up the ramp, to determine the threshold at which the speed of the occupied wheelchair (with and without the device in place) was sufficient to induce a forward tip down the step. Forward tips occurred at a mean (+/- 1 SD) threshold speed of 0.77 (+/- 0.06) m/s with the device and at 0.38 (+/- 0.04) m/s without it, a mean difference of 0.39 (+/- 0.07) m/s (p less than 0.0005). This preliminary study suggests that such a wheelchair feature might improve the safety of wheelchairs in conditions involving inadvertent loss of caster support, as when they drop off a stair or ledge. PMID- 2308083 TI - The effects of hearing aids on speech discrimination in noise by normal-hearing listeners. AB - This investigation measured the degree to which hearing aids degrade speech discrimination in noise. Ten normal-hearing subjects were tested for speech reception thresholds (SRT) in noise. The tests were repeated under two aided conditions: one used binaural behind-the-ear (BTE) aids, the other an experimental binaural high-fidelity aid fitted with in-the-ear transducers. To assess the loss of any directional cues under aided conditions, a test environment producing directional cues in both horizontal and vertical planes was employed. Results indicated a 3 dB deterioration of speech-to-noise ratio for frontal speech with the BTE aids. Despite this, mean SRTs, when averaged over several listening directions, differed by less than 1 dB from unaided levels under both aided conditions. This suggests that improvements in hearing aid fidelity and directional performance beyond that available in current BTE aids will do little to improve speech discrimination in noise, although other benefits may accrue. PMID- 2308084 TI - Articulated cadaveric bones as a structural endoskeleton in an ankle-foot prosthesis: a preliminary report. AB - This report describes the construction and evaluation of an ankle-foot prosthesis using human cadaveric bones as the endoskeleton inside a fiber-reinforced vulcanized rubber shell. Cadaveric bones and exhumed skeletal bones were used. Three designs were fabricated, subjected to radiographic evaluation, and underwent 4-week field trials of normal daily use by a unilateral below-knee amputee. The rubber shell retained the position of the bones, permitted movements at the joints in various stages of the stance phase, and restored the bones to their neutral position when the foot was unloaded. The cadaveric prosthesis provided for plantar flexion of the foot when the heel was loaded and for locking of the joints to restrain excessive movement when the foot came to rest. While fresh cadaveric bones withstood all the stresses of active walking, exhumed macerated bones fractured and fragmented with use. PMID- 2308085 TI - Operator performance in myoelectric control of a multifunction prosthesis stimulator. AB - In this paper, a microcomputer-based system is described which facilitates the evaluation of different myoelectric control strategies. The system is based on an IBM-PC/AT microcomputer which generates and develops tracking targets, processes and displays the operator's response, and computes tracking performance. The dynamics of the prosthetic elbow, hand, and forearm are simulated in software which drives a stick figure in response to the operator's input. Performance is measured in terms of integral absolute error in target-response match. Control strategies to simulate different systems are easily modified through software and are evaluated under identical conditions. As a test of this evaluation system and to obtain some comparative data on control strategies, four strategies which are either in use or proposed for use are evaluated. The test procedure is divided into a control training session and a control evaluation session. Data collected from groups of three normally-limbed subjects per strategy over a period of five control evaluation sessions are presented. The results of this evaluation are discussed and improvements in the evaluation system suggested. PMID- 2308086 TI - Cuspal flexure associated with amalgam restorations. AB - Cavity preparation causes cuspal flexure under simulated occlusal loads. During amalgam condensation, the dentist exerts forces on the tooth. After condensation, dental amalgam undergoes dimensional changes. We measured possible changes in the cuspal position of premolars during and after their restoration with dental amalgam. Strain gauges were attached to the buccal surfaces of the teeth, and a direct reading of the strain and a simultaneous time-strain curve were obtained. Measurements were taken at the onset of amalgam condensation and continued for 24 hours. The amalgam was then removed from the teeth, and a subsequent reading was made. On the basis of this model, we found that the use of amalgam as a restorative material caused a static load on the cusps of the teeth brought about their consequent permanent deformation. After amalgam removal, we observed complete elastic recovery for all the treated teeth. PMID- 2308088 TI - The tear resistance of various impression materials with and without modifiers. AB - In this study, we measured the tear resistance of several commonly used impression materials. In the first part, a trouser-leg tear test was used to determine tear energies for 15 impression materials in three major groups (polysulfides, addition-reaction silicones, and polyethers). One brand of polysulfide demonstrated the highest tear resistance. In general, generic types of impression material could not be ranked according to tear energy. In the second part of the study, we measured the effect of the addition of a system modifier (retarder/thinner) on the tear resistance of four addition-reaction silicones and two polyethers. Retarder/thinners significantly reduced the tear resistance of five of the six materials tested. PMID- 2308087 TI - An experimental study on the influence of the derived casts on the accuracy of different recording materials. Part I: Plaster, impression compound, and wax. AB - An experimental study was conducted to analyze the accuracy of transferring jaw relations with recording materials and the derived casts. A specific measuring system was designed to determine three-dimensional deviations of the condyles of an articulator. Four interocclusal recording materials were analyzed after various storage periods. The results indicated that the accuracy of the derived cast had a critical influence on the accuracy of the transferred jaw relations. None of the materials were reliable; the most accurate material generated deviations of approximately 300 microns. PMID- 2308090 TI - Sex difference in intercondylar distance. AB - Intercondylar distances that had been determined by means of the Minigraph and Simulator instruments were statistically compared for 130 men and 130 women. The mean intercondylar distance for men was 108 mm (SD = 7.2, SE = 0.6) and for women, 102 mm (SD = 7.4, SE = 0.6). The difference was highly significant (p less than 0.0001). It was hypothesized that adjustable articulators that have a lower limit of 90 mm for the intercondylar distance adjustment will not be adjustable for 5% of women having a smaller intercondylar distance. An articulator with a lower limit of 96 mm will not be adjustable for 20% of women and 5% of men. An adjustment range of 80 to 130 mm is suggested that, on the basis of the data gathered from this study, would miss only one woman in 10,000 at the lower limit and one man in 10,000 at the upper limit. PMID- 2308089 TI - Influence of ceramic thickness on the polymerization of light-cured resin cement. AB - The curing of two light-activated resin cements under two ceramic materials was examined to assess the influence of ceramic thickness on polymerization. The degree of resin cure was determined by microhardness measurements (Knoop) on resin cement samples cured under five ceramic thicknesses with light exposures of 30 to 120 seconds. These cements cured under thin ceramic specimens with recommended exposures. With thick ceramics, both cements cured better under the glass-ceramic, but neither reached a level of maximum cure under the porcelain. PMID- 2308091 TI - The influence of clinical variables on patients' satisfaction with complete dentures. AB - The effect of the technical quality of complete dentures and the physical condition of the mouth on patients' satisfaction was investigated in 130 patients who received new complete dentures. A moderately positive correlation was found between satisfaction of the patient and quality of the dentures. However, no correlation was found between the satisfaction of the patient and the physical condition of the mouth. PMID- 2308092 TI - Prosthetic and surgical management of osteogenic sarcoma of the maxilla. AB - Maxillary surgical defects resulting from resection of oral neoplasms vary in size from small perforations of the hard and soft palate to complete removal of these structures. Osteogenic sarcoma is of unknown etiology and is a rapidly growing tumor that may produce pain, paresthesia, and anesthesia. The recommended treatment of radical resection often results in defects that produce significant orofacial disfigurement. These defects, regardless of size, present significant functional disability, with compromised esthetics, mastication, and deglutition. Restoration with a maxillary obturator prosthesis can reestablish the physical separation between oral and nasal cavities and, in soft palate defects, enable normal palatopharyngeal function. Most patients can be rehabilitated successfully with restoration of speech and swallowing to normal levels and significant improvement in appearance. PMID- 2308093 TI - An evaluation of the surface characteristics of a facial prosthetic elastomer. Part II: The surface texture. AB - Silicone elastomers do not have an inherent surface texture but take on the surface texture of the surface against which they are processed. This study compares the surface texture of Cosmesil material, a purpose-designed facial prosthetic elastomer, and Molloplast-B material, which is a well-established material for use in the clinic. We used a profilometer to determine the roughness average, maximum roughness, and waviness of the dies, control, gypsum, and silicone test surfaces. Statistical analyses of results involved multivariate analyses of variance and Tukey's procedures to compare roughness average, maximum roughness, and waviness (in all cases p less than 0.05). The results showed that the silicone elastomers, Cosmesil and Molloplast-B, have similar surface characteristics. The only statistically significant difference was in waviness (Molloplast-B, means = 10.82 microns; Cosmesil, means = 12.82 microns). The gypsum surface yielding the most satisfactory result was the surface that had been treated with silicone paste separator. On the basis of surface characteristics, Cosmesil material is likely to cause no more surface trauma of the tissue against which it is placed than the use of Molloplast-B material. PMID- 2308094 TI - Use of protrusive splint therapy in anterior disk displacement of the temporomandibular joint: a 1- to 3-year follow-up. AB - Sixty-eight patients, who were determined clinically (by the presence of audible and palpable-joint sounds) and arthrographically to have meniscus displacement with reduction, had protrusive splints constructed, and the results were evaluated for a minimum of 1 year to a maximum of 3 years. Eighteen additional patients, arthrographically determined to have meniscus displacement with reduction, served as a nontreatment group for comparison. Odds ratios were calculated to compare the proportions of subjects who experienced follow-up symptoms on the two regimens. Results indicated that with splint therapy there was a statistically significant reduction of the intensity of jaw joint pain, temporal headache, ear pain, and pain in front of the ear, and there was a decrease in the probability of a closed lock condition developing. Splint therapy is less likely to reduce frontal headache, neck pain, and clenching of teeth. PMID- 2308095 TI - Surface electromyographic electrode pair with built-in buffer-amplifiers. AB - By means of a surface electrode with an operational amplifier, a new electrode unit suitable for an electromyographic-biofeedback apparatus and for portable electromyography used outside a Faraday cage was developed. The operational amplifier, which has an output impedance lower than 10 ohms, functions as an efficient buffer amplifier and is able to protect the EMG signals from background noises. This new electrode unit is small (32 x 12 x 5 mm), waterproof, and inexpensive. Because its structure is simple, it can be built in any laboratory. PMID- 2308096 TI - Multidimensional internal setting expansion of a phosphate-bonded casting investment measured with strain gauges. AB - Strain gauges were used to determine the setting expansion of phosphate-bonded casting investments. The gauges were placed at the approximate site of the wax pattern. The isotropy of the expansion was evaluated with multidirectional strain gauges that measured the difference in expansion in two orthogonal directions. A large difference was found between the setting expansion measured externally (1% to 1.5%) and the method described here (0.01%). For casting rings lined with a nonasbestos layer, no statistically significant differences were found in the setting expansion parallel to the long axis of the ring and the expansion in the direction perpendicular to the long axis. PMID- 2308097 TI - Modification of a crown remover. PMID- 2308098 TI - Enlightening article by Drs. Rieger, Adams, Kinzel, and Brose. PMID- 2308099 TI - Report of the Committee on Scientific Investigation of the American Academy Restorative Dentistry. PMID- 2308100 TI - Management and care of pregnant psychiatric patients. PMID- 2308101 TI - Exploring expressed emotion. Does it contribute to chronic mental illness? PMID- 2308102 TI - Ethical guidelines for the Colorado Society of Clinical Specialists in Psychiatric Nursing. PMID- 2308103 TI - Licensed psychosocial technicians (LPT) PMID- 2308104 TI - Professions, professional associations, and professionals. PMID- 2308105 TI - At risk: children of the mentally ill. PMID- 2308106 TI - Use of the pronoun "her" when indicating a possessive nature for the generic noun nurse. PMID- 2308107 TI - Anorexia nervosa support group: providing transitional support. PMID- 2308108 TI - Research involving patients. Summary and recommendations of a report of the Royal College of Physicians. AB - The careful study of disease as it occurs in patients, and the equally careful scrutiny of the effects of treatment, are an indispensable part of the continuing process of improving the efficiency of diagnosis and the effectiveness of treatment. Most patients realise that experience gained from their own case may contribute to their personal benefit or to that of society and, if asked, readily agree to take part in research into their condition. Accordingly, a patient who willingly participates in research has the status of a volunteer similar to that of a healthy person so that some of the questions relating to selection, consent, conduct of research and compensation in the event of injury are similar to those addressed in the College's report on Research in healthy volunteers, published in 1986. It is important to realise, however, that the patient is in a position of at least partial dependence which may affect the degree of voluntariness of collaboration, and also that there is a risk that enthusiasm on the part of the researcher could lead to undue persuasion or incomplete declaration of the facts. Furthermore, the patient's ability to give consent to participate in research may be impaired by illness. For these and other reasons, the College has prepared a separate report addressing the special problems of Research involving patients. A balance has to be struck between the benefits which may flow from properly conducted research, and the risk of infringing the autonomy, or of causing harm to the individual patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308109 TI - Stroke. Towards better management. Summary and recommendations of a report of the Royal College of Physicians. AB - All doctors, and most of their patients, are familiar with the consequences of stroke. In 1985 more than 70,000 men and women over the age of 65 died after a stroke and only one third of the survivors of stroke made a good recovery. It is thus a major source of chronic disability, placing a very heavy burden on patients' relatives and friends and consuming a great deal of NHS resources. The purpose of this Report is to set out guidelines for the clinical, radiological and pathological assessment of stroke, to suggest how to care for and rehabilitate patients who have suffered a stroke, and to evaluate and recommend measures for its prevention. The Report emphasises the need to use standard terms for the clinical description and classification of stroke, and the assessment of degrees of disability. It traces its changing epidemiology in the UK and in other countries and assesses the significance of putative risk factors such as hypertension, smoking, obesity, alcohol, diabetes, serum cholesterol, oral contraceptives and ischaemic heart disease. It sets out the indications for admitting patients to hospital and how they should be investigated, including the value of CT scanning at different intervals after the stroke has occurred. The Report describes the organisational aspects of the care of stroke patients during the acute phase, in the early recovery phase and in the longer term rehabilitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308110 TI - Proposed taxonomy of audit and related activities. AB - The quality of the current debate on medical audit has been compromised by semantic confusion. A simple taxonomy is suggested for six frequently cited terms: review, audit, evaluation, surveillance, appraisal and monitoring. Review is usually a clinically based professional scrutiny of a particular service. Continuous peer review is audit, which may be internal or external. Evaluation involves measuring health indices in relation to a reference point, such as an objective or a control group, and has a strong statistical or epidemiological flavour, as has surveillance which may be regarded as continuous evaluation. Appraisal is the managerial form of evaluation, while monitoring is its routine counterpart. Thus, review and audit are primarily clinically oriented activities, evaluation and surveillance tend to be more epidemiological, and appraisal and monitoring are largely managerial. Review, evaluation and appraisal may be described as one-off quality assessment methods, and audit, surveillance and monitoring as routine ones. This classification attributes a distinct theoretical identity to each of the six categories though they are not mutually exclusive. It also delineates boundaries between the necessarily separate professional worlds inhabited by clinicians, public health staff and managers, and places various quality assessment methods within appropriate time-frames. The scheme preserves the fundamental integrity of the six activities which collectively comprise the intelligence gathering arm of quality assurance. PMID- 2308111 TI - Acute medical admissions: changes following a sudden reduction in bed numbers at Northwick Park Hospital. AB - The aim of this study was to gather information on the consequences of hospital bed closures on acute admission patterns. Each November during 1986-1988 we carried out a survey of requests and referrals for acute medical admission to Northwick Park Hospital (NPH). Between the first study in 1986 and the second study in 1987, 15 acute medical and 16 surgical beds were closed. In 1986 the hospital was 'full' and closed overnight to admissions from general practitioners (GPs) on 3/25 days. In 1987 this had increased to 16/27 days and in 1988 it was closed overnight on 20/31 days. Because GPs found it unreasonably difficult to admit patients to NPH, the number of patients referred by them fell from 55.8% of all admissions to 49.8% and 44.3%, while the number of self-referred patients rose from 27.1% to 34.5% and 39.1%. An increasing proportion of elderly patients had to be admitted to acute medical beds: those over 75 years of age represented 24.8% of admissions in 1986, 43.7% in 1987, and 43.8% in 1988. These changes have had important effects on our medical practice, and we suggest that audits of this type are necessary to quantify these changes. We make suggestions for improving such medical audits in the future. PMID- 2308113 TI - Quality of life following liver transplantation: a preliminary report. AB - Although the quality of life attained after heart transplantation has been assessed, there is no equivalent information for recipients of liver grafts in this country. In this paper we report a cross-sectional survey of 81 adult patients in the Cambridge/King's College Hospital joint programme using the Nottingham Health Profile which is a validated measurement of the quality of life. The results show the quality of life to be high, and broadly similar to the levels expected in the general population. The data suggest an increase in the problems related to physical mobility (two-fold) and a reduction in problems of emotional reaction (a halving). PMID- 2308112 TI - Clinical outcome and costs of care in radioiodine treatment of hyperthyroidism. AB - The long-term clinical outcome and costs of treatment of hyperthyroidism with radioiodine have been examined in two cohorts of patients from Sheffield and Scotland. The majority of patients in both series were considered to have Graves' disease. The Sheffield patients (660) were included in a trial of three radioiodine dose regimens of 3,500 (312), 7,000 (323) and 14,000 (25) rad determined using a formula for accurate dosimetry. The Scottish patients (3,920) drawn from five centres in Aberdeen, Dundee, Edinburgh, Glasgow and Inverness were treated using an arbitrary scale, for the activity of radioiodine administered, related to goitre size. Their results are grouped into five MBq 'dose' bands: 37-185, 186-370, 371-555, 556-740 and 741+. The proportion of patients with persistent hyperthyroidism was higher in both cohorts for low-dose radioiodine regimens, but 15-25% of patients who received high doses showed persistent hyperthyroidism. Early and late onset hypothyroidism was lower after low doses but differences between the treatment groups were small in terms of clinical benefit. Total morbidity at 10 years follow-up, in terms of hyperthyroidism, and hypothyroidism, was highest after low-dose therapy. There was little variation in total costs, but patient costs were lowest for the Scottish regimen and highest for low-dose therapy. A dose of at least 370-555 MBq which will ensure early elimination of hyperthyroidism will also limit the medical workload and total costs. PMID- 2308114 TI - Orthopaedic geriatric care--is it effective? A prospective population-based comparison of outcome in fractured neck of femur. AB - Orthopaedic geriatric care has become widely accepted despite relatively little formal evaluation. In the East Dorset health authority all patients with fractured neck of femur initially share common orthopaedic facilities but only those from one geographical sector have subsequent access to an orthopaedic geriatric unit, patients from the other sector receiving standard care. We have carried out a prospective population-based comparison of the outcome of 155 consecutive incident cases of fractured neck of femur aged over 65 years. On admission to hospital the two populations were similar in respect of age, sex, fracture type, social status, medical and orthopaedic problems, mental status and dependency (Clifton assessment procedure for the elderly). Multiple regression analysis showed that the mean length of stay was 9.5 days shorter in patients from the sector with access to orthopaedic geriatric care (p less than 0.05, 95% confidence interval 0.6 to 18.4 days). This reduction was not due to any difference between the two groups as regards dependency or the level of support provided on discharge. There was no difference in outcome at 6 months post operatively in terms of mortality, functional outcome (pain and mobility), change in dependency or social status. We conclude that in the East Dorset health authority this combined approach has resulted in a significant reduction in the length of inpatient stay without any other apparent effect on patient outcome. PMID- 2308115 TI - An advanced resuscitation training course for preregistration house officers. AB - Preregistration house officers need to be able to manage the first 5-10 minutes of a cardiac arrest. A course has been designed based on the recommendations of the Resuscitation Council UK 1984 and the format of the American Heart Association advanced cardiac life support course. Fifty-nine newly qualified doctors from the same medical school class were studied in two consecutive groups: Group 1 (n = 31) were commencing their first post and Group 2 (n = 28), whose first preregistration post had been at other hospitals without practical resuscitation training, were commencing their second post. They were pretested and taught in three 2-hour sessions. Five months later they were tested to measure retention of knowledge and skills. Before training there was no difference in knowledge between the two groups but Group 1 were more skilled. The knowledge and skills of both groups immediately after training were significantly improved and at 5 months skills were subject to modest decay only. Experience of managing cardiac arrests was not a substitute for formal practical training. PMID- 2308116 TI - Medicine and ethics. PMID- 2308117 TI - Black looks ... at when life begins. PMID- 2308119 TI - Right ventricular outflow obstruction caused by primary cardiac neoplasia. Clinical features in two dogs. AB - Obstruction to pulmonary blood flow as a result of neoplasia in the right ventricular outflow tract is described in two dogs. Whereas one dog had exertional syncope and a systolic ejection murmur, the other had signs of congestive failure and hypoxia. In both animals the mass was detected in the right ventricle with two-dimensional echocardiography and confirmed angiographically. Although rare, primary right ventricular neoplasia represents a potentially treatable form of cardiac disease and should be considered as a cause of acquired outflow tract obstruction. PMID- 2308118 TI - Long-term survival of a cat receiving a renal allograft from an unrelated donor. AB - A 6-year-old, spayed female Persian cat in terminal renal failure was referred to the Veterinary Medical Teaching Hospital for renal transplantation. An allograft from an unrelated donor was placed in the right iliac fossa and cyclosporine and prednisolone were administered as immunosuppressive agents. More than 18 months after surgery the cat was clinically normal and azotemia was absent. PMID- 2308120 TI - Therapy of immune mediated thrombocytopenia. A retrospective study of 15 dogs. AB - Fifteen dogs with immune mediated thrombocytopenia (IMT) were studied retrospectively. All dogs had a thrombocyte count below 50,000/microliters when response to therapy was studied. Platelet counts greater than 50,000/microliters were present in all dogs within 2-9 days of initiating medical therapy. Eight dogs experienced a single episode of thrombocytopenia and seven dogs relapsed over the following 5 to 24 months. Clinical parameters from dogs that experienced a single episode of IMT were compared with data from dogs that relapsed to determine whether any information would identify dogs that were prone to relapse. Signalment, severity of thrombocytopenia, and time to achieve a platelet count above 50,000/microliters were found not to differ (P greater than 0.05) between these two groups. Five of the seven dogs with relapsing IMT were splenectomized after 2 to 4 episodes (mean, 2.8 +/- 0.8) of thrombocytopenia over 2 to 14 months. The postoperative progress of these five dogs was followed for 6 to 17 months. Platelet counts were sustained above 200,000/microliters in 4/5 after splenectomy and it was possible to discontinue medical therapy in these dogs. In comparison, the 2 relapsing IMT cases that were not splenectomized continued to require intermittent immunosuppressive therapy. We conclude that signalment and routine pretreatment laboratory test results are not useful in distinguishing dogs with relapsing IMT from those that will experience one episode of IMT. Seemingly, splenectomy is useful in the management of dogs with relapsing IMT. PMID- 2308121 TI - Partial masking of the canine electroretinogram by oscillatory potentials. The problem of frequency bandwidth. AB - Recording the electroretinogram (ERG) in dogs has become a standard procedure in clinical ophthalmology. The ERG provides highly objective information about retinal function that is otherwise unobtainable from dogs. However, problems may be encountered in measuring the latencies amplitudes of the a and b waves, depending upon the amplifier bandwidth used to record the potential. Superimposed on the canine ERG are other complex retinal potentials, some of which have higher frequency spectra than those that give rise to a and b waves. Whereas an amplifier bandwidth of 1.0 to 100 Hz or more insures that the slower components of the ERG are recorded, it also allows higher frequency oscillatory potentials (OP) to be recorded on the b wave. The OP cause a notching in the peak of the b wave thus necessitating a decision about how to measure the b wave. Bandwidth characteristics of the ERG and OP are presented and some possible methods for measuring the OP-contaminated ERG are discussed. PMID- 2308122 TI - Transfer of free vascularized bone and skin-bone autografts: experiences in the application of external fixation apparatus. AB - The results of transfer of free vascularized bone and skin-bone autografts in 95 patients with defects (54) and nonunions (41) of tubular bones of different genesis are presented. In 71 cases, an external fixation apparatus was used for purposes of osteosynthesis. In 50 cases, the Ilizarov apparatus was applied prior to osteoplasty to correct deformity and fully or partially to correct a shortening of the extremity bone segment. In seven cases, lengthening of the bone segment was performed using an external fixation apparatus after osteoplastic reconstruction of the defect. Treatment was completed in 76 cases (80.0 percent); of these, the outcome was positive in 89.5 percent of cases. Failure was recorded in 10.5 percent of cases. The advantages of using an external fixation apparatus in combination with vascularized bone and osteocutaneous autografts are discussed. PMID- 2308123 TI - Resurfacing difficult wounds: selective use of the posterior tibial flap. AB - The posterior tibial flap is a type C fasciocutaneous flap from the medial calf with the posterior tibial vascular bundle as its pedicle. Most of the skin perforators, 1 to 3 in number, can be found in the middle third of the leg, with an average diameter of 0.8 mm and an average length of 22 mm. The posterior tibial artery ranges between 1.5 and 2.0 mm in diameter, although it is absent in 8 percent of limbs. Since the saphenous nerve is taken with the flap, this is an innervated flap. The flap can be transferred as a free flap or a pedicled flap. The reversed-flow pedicled flap has an average pedicle length of 8 cm. The posterior tibial flap is a reliable, large, thin, innervated flap and can be raised with the patient supine. Case reports are presented of six patients who received a free flap transfer and of one patient who received a reversed-flow pedicled flap. There were two cases of heel ulcerations, two crushed hands, one chronic ulceration and osteomyelitis of the tibia, one burn contracture of the neck, and one salvage flap for diabetic gangrene of the hand. PMID- 2308124 TI - Deltoid sensory flap. AB - Eight patients were treated using the deltoid sensory flap for soft-tissue injury of the extremities. The results were one-stage reconstructions of soft tissue extremity injuries. Protective sensibility was provided to the reconstructed area; there was no limitation of motion of the shoulder after the procedure; and primary closure of the donor site was feasible. The advantages of the deltoid sensory flap exceed those of other reconstructive procedures that are used in areas where sensibility is essential. PMID- 2308125 TI - Increased flap survival after sensory denervation with capsaicin accompanied by delay. AB - The effect of capsaicin, combined with delayed surgical procedures, was studied in adult rats. After denervation of the experimental subjects' cutaneous nerves with capsaicin, the time required for the flaps to become completely necrotic was prolonged; when accompanied by delayed flap raising for a period of up to eight weeks, the flap survival rate was increased. Although there were no significant differences in flap survival between the control and the capsaicin animals undergoing flap raising with no delay, increased vascularity and flap survival were confirmed in capsaicin animals in whom procedures had been delayed. Maximum flap survival was found in capsaicin animals undergoing a six-week delay in the procedures. These results suggest that sensory nerves play an important role in flap survival, perhaps in the areas of flap vascular supply and tension control of the A-V shunt in the microcirculation of a flap. PMID- 2308126 TI - Patterns of recovery of sensibility in free flaps transferred to the foot: a prospective study. AB - In a prospective study, the recovery of mechanical sensibility in five free flaps transferred to the foot was assessed qualitatively and measured with a quantitative method. The detection thresholds for 20, 80, and 240 Hz vibration frequencies were determined preoperatively from the recipient area and postoperatively from the flap at intervals of two to six months up to 14 to 21 months. Detection thresholds to mechanical vibration could be measured in the flaps immediately after operation before any sensory innervation could have taken place. The immediate postoperative thresholds were similar to the preoperative values obtained from an existing full-thickness defect; and where surgery had created a considerably deeper defect, they were elevated. The recovery of mechanical sensibility in the transferred flaps was found to be slow and incomplete. In three patients, after one year of follow-up, the flaps showed qualitative improvement in sensibility accompanied by a moderate lowering of detection thresholds obtained with 240 Hz vibration frequency. In two other flaps, there was no improvement in sensibility. In the reconstructions that had good soft-tissue stability, the flap was resistant to breakdown even before sensory recovery. PMID- 2308127 TI - The histochemical study of rat sciatic nerve cholinesterase in degeneration and regeneration. AB - With a modified, less time-consuming, Karnovsky-Roots method, this study evaluated the reduction and recovery of rat sciatic nerve cholinesterase (ChE) in degeneration and regeneration. Characteristics of motor fascicles included not only partial staining of acetylcholinesterase (AchE) in the axon, but also a small amount of more intense staining of butyrylcholinesterase (BuchE) in the unmyelinated fibers, scattered between the myelinated fibers in a spot or fleck form. Characteristics of sensory fascicles included more intense staining of BuchE in the unmyelinated fibers, (appearing as irregular balls or pieces), and a scattering between unstained myelinated fibers. Mixed fascicles had characteristics of both motor and sensory fascicles. Unmyelinated fibers exhibited BuchE activity, but myelinated fibers exhibited AchE activity. Preparation time for a specimen to react to ChE-positive staining was about 1 to 2 hr; the method is very suitable for diagnosis during surgery. After nerve transection, AchE activity at the distal nerve end began to reduce gradually; no AchE could be tested after two weeks. But BuchE activity in unmyelinated fibers could be found until 30 days after transection. After epineurial suturing of the peripheral nerve transection, new AchE activity could be found at the anastomosis site until about two weeks and at 1 cm distal to the anastomosis site until about three weeks. It became more intense with the passage of time and, at about six weeks, regenerated AchE-positive myelinated fibers could be seen at the distal end of the nerve. PMID- 2308128 TI - Perfusion of free flaps with heparinized whole blood during ischemic storage. AB - This study was designed to investigate the use of heparinized whole blood as a perfusate for extending the tolerable ischemic interval of free flaps. Unilateral free groin flaps stored at 20 degrees for 30 hr were used in four groups of 12 rats each. One group served as a control while a second involved systemic heparinization immediately prior to raising the flap for storage. The third and fourth groups underwent a brief perfusion (10-30 min) with anticoagulated whole blood midway through the ischemic interval (15 hr); one of these groups involved temporary revascularization to the arterial system of a donor heparinized rat. The fourth group received hand-perfused anticoagulated (with heparin and citrate) whole blood administered through a cannula placed in the flap artery. After the 30-hr interval, flaps were replanted to the original groin site with standard microvascular technique. Percentages of the numbers of surviving flaps were: 8 percent for controls, 58 percent for both preheparinized and donor-perfused flaps, and 92 percent for the hand-perfused group. The authors conclude that anticoagulated blood within the flap vasculature during ischemic storage can improve the chance for viable reperfusion after replantation, and may offer a safeguard against the no-reflow phenomenon after extended ischemia. PMID- 2308129 TI - Laser-assisted microsurgical anastomoses in traumatized blood vessels. AB - Technological advances have made CO2 laser-assisted microvascular anastomoses (LAMA) feasible. This study seeks to compare results of LAMA versus CSMA (conventional suture microsurgical anastomosis) in traumatized vessels. Using a rat model, femoral arteries and veins were either crushed and transected or divided by avulsion and then repaired by either LAMA or CSMA. LAMA resulted in higher patency rates than CSMA at early postoperative observation periods. With time, the patency rates improved in both groups and, by the end of the study, the patency rates were equivalent. These findings indicate that the laser technique may be a better option when working with traumatized vessels because of the critical nature of early patency rates. The improved results may be due to a reduction of suture material at the anastomotic site when using the laser technique. Some physiologic aspects of vessel thrombosis, recanalization, and the role of collateral circulation are discussed. PMID- 2308130 TI - The relationship of functional return to varying methods of nerve repair. AB - This experimental study correlated varying methods of nerve repair with the degree of functional return using the rat sciatic nerve as a model. Six groups of adult male Sprague-Dawley rats (300 to 350 g) had their left sciatic nerve crushed (Group 1), transected and not repaired (Group 6), or transected and repaired using four methods that varied the degree of axonal alignment (Groups 2, 3, 4, and 5). Functional return was evaluated weekly using the sciatic functional index (SFI) and histology. Group 1 (crush) had a significantly better functional return than the other groups (p less than .001). Group 6 (no repair) had a significantly worse functional return than the other groups (p less than .001). Groups 2, 3, 4, and 5, regardless of the precision of axonal alignment, experienced the same degree of functional return (p less than .05). In all groups, with the exception of Group 1 (crush), the degree of functional return was poor. As multiple modifications in conventional microsurgical neurorrhaphy have not resulted in a significant functional improvement, factors not addressed by current techniques apparently compromise clinical results. Further improvement in the results of neurorrhaphy will require modifications in our techniques beyond presently conventional microsurgical methods. PMID- 2308131 TI - Preoperative cooling and storage of amputated digits. PMID- 2308132 TI - Two-dimensional oblique cut: a simple method helps anastomosing small vessels. AB - A simple method involving a two-dimensional oblique cut is introduced to help anastomosing tiny vessels. This method can enlarge the cut ends, reduce vessel constriction, make the lumen easier to see, and stagger the front and back edges. PMID- 2308133 TI - NMR studies of the conjugation of mechlorethamine with glutathione. AB - Many cancer cells are resistant to chemotherapeutic treatment with mechlorethamine and other alkylating agents. These drug-resistant cells often show an increase in the intracellular concentration of glutathione and an increase in the activity of glutathione-S-transferase when compared to the sensitive cells. Both of these components are thought to be involved with inactivation of the drug either through conjugation with glutathione or by hydrolysis. NMR spectroscopy was used to monitor the nonenzymatic conjugation of mechlorethamine with glutathione. Several intermediates along the pathway to the doubly glutathione substituted mustard, including both mustard-aziridinium adducts, can be observed. The assignment of the 1H NMR spectrum of these adducts are presented. At 30 degrees C, pH 7.0, no hydrolyzed mustard was detectable. With the use of 13C-labeled mustard, the conjugation reaction can be shown to proceed through an aziridinium intermediate rather than by direct nucleophilic substitution. PMID- 2308134 TI - Synthesis of N-[N-(4-deoxy-4-amino-10-methylpteroyl)-4-fluoroglutamyl]- gamma glutamate, an unusual substrate for folylpoly-gamma-glutamate synthetase and gamma-glutamyl hydrolase. AB - N-[N-(4-Deoxy-4-amino-10-methylpteroyl)-4-fluoroglutamyl]-ga mma-glutamate has been synthesized and its ability to serve as a substrate for folylpolyglutamate synthetase and gamma-glutamyl hydrolase has been investigated. It was anticipated that this compound would be a substrate for both of these enzymes. Although the title compound proved to be a good substrate for folylpolyglutamate synthetase, hydrolysis catalyzed by gamma-glutamyl hydrolase was unexpectedly slow. These results suggest the use of fluoroglutamate-containing peptides as hydrolase resistant folates or antifols in a variety of chemotherapeutic regimens. PMID- 2308135 TI - A structure-affinity study of the binding of 4-substituted analogues of 1-(2,5 dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors. AB - With [3H]ketanserin as the radioligand, structure-affinity relationships (SAFIRs) for binding at central 5-HT2 serotonin receptors (rat frontal cortex) were examined for a series of 27 4-substituted 1-(2,5-dimethoxyphenyl)-2-aminopropane derivatives (2,5-DMAs). The affinity (Ki values) ranged over a span of several orders of magnitude. It appears that the lipophilic character of the 4-position substituent plays a major role in determining the affinity of these agents for 5 HT2 receptors, 2,5-DMAs with polar 4-substituents (e.g. OH, NH2, COOH) display a very low affinity (Ki greater than 25,000 nM) for these receptors, whereas those with lipophilic functions display a significantly higher affinity. The results of these studies prompted us to synthesize and evaluate examples of newer lipophilic derivatives and several of these (e.g. n-hexyl, n-octyl) bind with very high (Ki values = 2.5 and 3 nM, respectively) affinities at central 5-HT2 sites. Although, 2,5-DMAs are generally considered to be 5-HT2 agonists, preliminary studies with isolated rat thoracic aorta suggest that some of the more lipophilic derivatives (e.g. the n-hexyl and n-octyl derivatives) are 5-HT2 antagonists. PMID- 2308136 TI - Binding of cis(1,2-diaminocyclohexane)platinum(II) and its derivatives to duplex DNA. AB - A theoretical study is presented for the binding of RR, SS, SR, and RS isomers 1,2-diaminocyclohexane (DAC) or cis-PtII(DAC) to DNA. cis-PtII(DAC) is ligated to N7(G) on two adjacent intrastrand guanine bases in a kinked pentamer duplex of DNA (AT, CG*, CG*, GC, AT). The relative stability of the complexes is determined by calculating the relative conformational energy of the cis-PtII(DAC)(DNA) complexes with molecular mechanics (MM) and the intrinsic binding or ligation energy with quantum mechanics (QM). The results suggest that the RR and SS isomers of PtII(DAC) adducts with DNA are more stable than the SR/RS isomer by 1.7 kcal/mol relative to the cis-PtII(DAC(H2O)2 aquated species. Calculations on the overall stability of these isomers show that the SS and RR isomers are 6.5 8.2 kcal/mol more stable than the SR/RS isomers when bound to DNA, and this is attributed to differences in the strain energy in the DAC rings. The theoretical analyses of these compounds correlate a small differential activity with the trend in intrinsic binding energies. The RR isomer is more active in B16 melanoma cells, and the SS is most active in L1210 leukemia, and in general the RR and SS isomers are more active than the SR and RS in most cell types. The fact that the activity is DNA dependent suggests that excision or repair mechanisms may be taking place and that additional mechanistic steps beyond molecular modeling and quantum mechanical calculations are required to fully understand the activity. These studies of molecular fit of cis-PtII(DAC) to DNA are used to suggest substituted DAC compounds that may yield similar binding characteristics. Modifications to yield DAC derivatives are recommended in anticipation that they may also exhibit activity. PMID- 2308137 TI - High potency dipeptide sweeteners. 1. L-aspartyl-D-phenylglycine esters. AB - Twenty esters of L-aspartyl-D-phenylglycine, as well as two substituted analogues, an o-fluoro and a p-hydroxy-phenylglycine ester, were prepared. The L aspartyl-D-phenylglycine (-)-alpha- and (+)-beta-fenchyl esters had the highest sweetness potency at 1200 and 3700 times that of sucrose, respectively. The high potency of these sweeteners is surprising as the phenyl group occupies a position previously believed to accommodate only much smaller groups. PMID- 2308138 TI - 4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent, selective, bioavailable class III antiarrhythmic agents. PMID- 2308139 TI - Neural networks applied to structure-activity relationships. PMID- 2308140 TI - Antioxidant-based inhibitors of leukotriene biosynthesis. The discovery of 6-[1 [2-(hydroxymethyl)phenyl]-1-propen-3-yl]-2,3-dihydro-5- benzofuranol, a potent topical antiinflammatory agent. AB - The leukotrienes, metabolites of arachidonic acid produced through the action of the enzyme 5-lipoxygenase, are important mediators of immediate hypersensitivity and inflammation. Among the variety of diseases in which the leukotrienes may play a symptomatic or causative role is the dermatological condition psoriasis, a chronic proliferative disease of the skin. This study reports the synthesis and comparative biological activities of various ortho-substituted phenols including 4-methoxyphenols, 6-hydroxy-1,2,3,4-tetrahydrobenzopyrans, 2,3-dihydro-5 benzofuranols, and 5-benzofuranols. The phenols prepared in this study were evaluated for their ability to inhibit the production of leukotriene B4(LTB4) in isolated human polymorphonuclear leukocytes (PMNs) and to inhibit a topical inflammatory response in the topical mouse ear (TME) model. In the former case, when the log IC50 was plotted versus the log of the octanol/water partition coefficient (log P), to eliminate the effect of lipophilicity, the 2,3-dihydro-5 benzofuranol ring system was shown to be more potent than the other ring systems examined throughout the range of partition coefficients studied. The ability to inhibit leukotriene production in vitro in human PMNs can be rationalized on the basis of a model that suggests that the observed inhibition is dependent on the kinetic ability of the inhibitor to reduce a radical species and on the fraction of inhibitor that is partitioned into the cell membrane. While the in vivo antiinflammatory activity as measured by the TME did not correlate with the in vitro data, it was felt that the TME represented a valuable measure of the ability of a compound to penetrate the skin to the site of an ongoing inflammatory response. Of the compounds synthesized in this study, 6-[1-[2 (hydroxymethyl)phenyl]-1-propen-3-yl]-2,3-dihydro-5-benzof uranol (1, L-651896) was chosen for further development. PMID- 2308141 TI - Preparation and anticonvulsant activity of a series of functionalized alpha aromatic and alpha-heteroaromatic amino acids. AB - We recently reported the potent anticonvulsant activity of (R,S)-alpha-acetamido N-benzyl-alpha-phenylacetamide (2b). Selectively substituted derivatives of this compound have now been prepared (23 examples) and evaluated in the maximal electroshock seizure (MES) and horizontal screen (tox) tests in mice. In several key cases, replacement of the alpha-phenyl substituent in 2b by a relatively small, electron-rich, heteroaromatic moiety led to a substantial improvement in the anticonvulsant potency of the drug candidate. The most active compounds were (R,S)-alpha-acetamido-N-benzyl-2-furanacetamide (2g) and (R,S)-alpha-acetamido-N benzyl-2-pyrroleacetamide (2i). After ip administration, the MES ED50 values for 2g (10.3 mg/kg) and 2i (16.1 mg/kg) compared well with phenytoin (9.50 mg/kg). Evaluation of the two individual enantiomers of 2g demonstrated that the anticonvulsant activity resided in the R stereoisomer. The low ED50 value (3.3 mg/kg) for (R)-2g contributed to the large protective index (TD50/ED50) observed for this drug candidate, which approached that of phenytoin. PMID- 2308143 TI - Selective inhibition of gamma-aminobutyric acid aminotransferase by (3R,4R),(3S,4S)- and (3R,4S),(3S,4R)-4-amino-5-fluoro-3-phenylpentanoic acids. AB - (3R,4R),(3S,4S)- and (3R,4S),(3S,4R)-4-amino-5-fluoro-3-phenylpentanoic acid (1a and 1b) were synthesized and studied as selective inactivators of gamma aminobutyric acid (GABA) aminotransferase. Neither compound caused time-dependent inactivation of the enzyme. Neither compound underwent enzyme-catalyzed transamination nor was fluoride ion eliminated from either compound by the enzyme. No 3-phenyllevulinic acid, the product of elimination of HF followed by enamine hydrolysis, was detected. However, both 1a and 1b were competitive reversible inhibitors of GABA aminotransferase; the Ki for 1a was smaller than the Km for GABA. These results suggest that 1a and 1b bind to the active site of GABA aminotransferase, but gamma-proton removal does not occur. Whereas (S)-4 amino-5-fluoropentanoic acid (AFPA) is a potent inhibitor of L-glutamic acid decarboxylase (GAD), neither 1a nor 1b at concentrations 40 times the Ki of AFPA caused any detectable competitive inhibition of GAD. Therefore, the incorporation of a phenyl substituent at the 3-position of AFPA confirms selective inhibition of GABA aminotransferase over GAD. PMID- 2308142 TI - Synthesis and anticonvulsant activity of 2-benzylglutarimides. AB - A series of 2-benzylglutarimides (4) and their N-methyl analogues (5) were prepared according to the Topliss scheme for the selection of benzyl substituents to maximize anticonvulsant activity. A total of 22 such compounds were subjected to initial (phase I) screening in mice against seizures induced by maximal electroshock (MES) and pentylenetetrazol (scMet) and in the rotorod assay for neurotoxicity. From this series of test compounds, 10 were advanced to quantitative (phase II) testing. Of these, 2-(4-chlorobenzyl)glutarimide (4b) emerged as the most promising anticonvulsant drug candidate by demonstrating both good anti-scMet and anti-MES activity combined with low neurotoxicity after intraperitoneal administration in mice. In drug differentiation tests, 4b was also effective in nontoxic doses against seizures induced by bicuculline, picrotoxin, and strychnine. When compared with the clinically useful drugs phenytoin, carbamazepine, phenobarbital, valproate, and ethosuximide, 4b exhibited an overall pharmacological profile most closely resembling that of valproate. PMID- 2308144 TI - Steroidal A ring aryl carboxylic acids: a new class of steroid 5 alpha-reductase inhibitors. AB - A series of 17 beta-carbamoyl-1,3,5(10)-estratriene-3-carboxylic acids has been prepared and evaluated in vitro as inhibitors of human and rat prostatic steroid 5 alpha-reductase (EC 1.3.1.30). Potent inhibition of the human enzyme, in particular, was observed and preliminary studies using rat enzyme suggest that the inhibition results from the formation of an enzyme-NADP(+)-inhibitor complex. The compounds were synthesized from estrone, generally employing a differentiated bis-triflate carbonylation strategy. PMID- 2308145 TI - Inhibition of steroid 5 alpha-reductase by unsaturated 3-carboxysteroids. AB - A series of unsaturated steroids bearing a 3-carboxy substituent has been prepared and assayed in vitro as inhibitors of human and rat prostatic steroid 5 alpha-reductase (EC 1.3.1.30). It is proposed that the observed tight binding of the 3-androstene-3-carboxylic acids is due to mimicry of a putative, high-energy, enzyme-bound enolate intermediate formed during the NADPH-dependent conjugate reduction of testosterone by steroid 5 alpha-reductase. These compounds were prepared through palladium(0)-catalyzed carbomethoxylations of enol (trifluoromethyl)sulfonates derived from 3-keto precursors. Modification of A and B ring unsaturation and substitution at C-3, -4, -6, and -11 was explored. Mono- and dialkylcarboxamides were employed as 17 beta side chains to enhance inhibitory activity with the human enzyme. PMID- 2308147 TI - Small peptide inhibitors of smooth muscle myosin light chain kinase. AB - The pentapeptide Ser-Asn-Val-Phe-Ala-OBzl has been identified as the smallest inhibitory peptide of myosin light chain kinase (MLCK) derived from the primary sequence of the light chain phosphorylation site. The specific contributions of individual amino acid side chains and backbone elements of this pentapeptide toward the stabilization of the enzyme-inhibitor (E-I) complex have been evaluated. The potency of these peptides as inhibitors of MLCK has been enhanced by the incorporation of synthetic nonnatural amino acids into the sequence. Finally, it has been demonstrated that these peptide sequences could be converted into pseudopeptides with synthetic nonpeptide subunits designed to mimic peptide bonds, and that certain pseudopeptides retained the high-affinity inhibition of the parent pentapeptides. PMID- 2308146 TI - Neuronal mapping of the heart with 6-[18F]fluorometaraminol. AB - The false neurotransmitter metaraminol labeled with fluorine-18 has been used to noninvasively assess regional adrenergic nerve density in the canine heart. Intravenous administration of 6-[18F]fluorometaraminol (FMR) results in high, selective accumulation of radioactivity in the heart; drug blocking studies with desipramine and reserpine confirm the neuronal locus of FMR. Iodine-125 labeled metaraminol, however, shows no selective accumulation in the canine heart. Positron emission tomography (PET) analyses with FMR of closed-chest dogs bearing left ventricular neuronal defects clearly delineate the region of neuronal impairment; blood perfusion in the left ventricle wall was homogeneous as determined by [13N]NH3 tomograms. The accumulation of FMR in regionally denervated dog heart correlates closely (r = 0.88) with endogenous norepinephrine concentrations. PET-generated 18F time-activity curves demonstrate marked kinetic differences between normal and denervated myocardium. FMR/PET analysis could be used to assess the heterogeneity of sympathetic innervation in human heart disease contingent on the development of FMR with sufficiently high specific activity to clearly avoid pressor activity. PMID- 2308149 TI - Hydroxamic acid inhibitors of 5-lipoxygenase: quantitative structure-activity relationships. AB - An evaluation of the quantitative structure-activity relationships (QSAR) for more than 100 hydroxamic acids revealed that the primary physicochemical feature influencing the in vitro 5-lipoxygenase inhibitory potencies of these compounds is the hydrophobicity of the molecule. A significant correlation was observed between the octanol-water partition coefficient of the substituent attached to the carbonyl of the hydroxamate and in vitro inhibitory activity. This correlation held for hydroxamic acids of diverse structure and with potencies spanning 4 orders of magnitude. Although the hydrophobicity may be packaged in a variety of structural ways and still correlate with potency, the QSAR study revealed two major exceptions. Specifically, the hydrophobicity of portions of compounds in the immediate vicinity of the hydroxamic acid functionality does not appear to contribute to increased inhibition and the hydrophobicity of fragments beyond approximately 12 A from the hydroxamate do not influence potency. The QSAR study also demonstrated that inhibitory activity was enhanced when there was an alkyl group on the hydroxamate nitrogen, when electron-withdrawing substituents were present and when the hydroxamate was conjugated to an aromatic system. These observations provide a simple description of the lipoxygenase-hydroxamic acid binding site. PMID- 2308148 TI - Synthesis and biological activity of novel quaternary ammonium derivatives of alkylglycerols as potent inhibitors of protein kinase C. AB - Alkylglycerols such as rac-1-O-octadecyl-2-O-methylglycerophosphochocholine (Et 18-OMe) have shown an inhibitory effect on the metastasis and growth of various cancer cell lines. Alkyl phospholipids have been shown to accumulate at the surface in several cell lines, the selectivity of which is still not clearly understood. A consequence of this action may lead to the inhibition of cell membrane related protein kinase C (PKC). The goal of this research was to develop ether lipid inhibitors of PKC to augment antineoplastic activity. This led to the synthesis and in vitro testing of a series of novel quaternary ammonium derivatives of alkylglycerols. The biological testing of these analogues on PKC stimulated with rac-1-O-oleoyl-2-O-acetylglycerol showed several analogues with inhibition comparable to that of Et-18-OMe. PMID- 2308150 TI - Synthesis, conformation, and immunosuppressive activities of three analogues of cyclosporin A modified in the 1-position. AB - The syntheses of three new cyclosporin A (CsA) analogues that contain novel MeBmt derivatives in the 1-position are described. The MeBmt analogue that contains an additional methyl group on C4, (2S,3R,6E)-4,4-dimethyl-3-hydroxy-2-(N methylamino)-6-octenoic acid (MeBm2t), was synthesized in four steps beginning with the reaction of Pmz-Sar-OtBu with (4E)-2,2-dimethyl-4-hexenal. The C4 desmethyl analogue of MeBmt, (2S,3R,6E)-3-hydroxy-2-(N-methylamino)-6-octenoic acid (MeBth), was synthesized in nine steps by a route based on the Sharpless chiral epoxidation procedure. The alkynyl derivative of MeBmt, (2S,3R,4R)-4 methyl-3-hydroxy-2-(N-methylamino)-6-octynoic acid (MeByt), was synthesized by a modification of the procedure described by Tung et al. for the synthesis of MeBmt. Each MeBmt analogue was protected as the N,O-acetonide and coupled with the hexapeptide Abu-Sar-MeLeu-Val-MeLeu-Ala-OBzl. The resulting heptapeptide was deprotected and coupled with Fmoc-D-Ala-MeLeu-MeLeu-MeVal-OH. The resulting undecapeptides were deprotected and cyclized to give the corresponding CsA analogues. Conformational analysis by 1D and 2D NMR methods was carried out for each analogue in chloroform, and the results are compared with the corresponding solution conformations of CsA and dihydrocyclosporin. The immunosuppressive activities of each analogue, determined in concanavalin A stimulated thymocytes, are lower than obtained for CsA. The results establish the important effect the methyl group and the double bond in MeBmt have on the solution conformation of the 1-position residue in CsA and on immunosuppressive activity. PMID- 2308152 TI - A family study of congenital X linked sideroblastic anaemia. AB - We report on the cytogenetic findings in a family study of pyridoxine responsive, X linked sideroblastic anaemia. An increase in the number of X chromosomes was observed in a small proportion of metaphases prepared from five female members, but these findings did not strictly correlate with the carrier status of the condition. No consistent cytogenetic abnormality could be identified or associated with this rare familial condition. The diagnosis and counselling of carriers of this condition is discussed. PMID- 2308151 TI - Search for consanguinity within and among families of patients with trichothiodystrophy associated with xeroderma pigmentosum. AB - The association of two rare hereditary disorders, trichothiodystrophy (TTD) and xeroderma pigmentosum (XP), was found in four patients from three families, apparently unrelated but living in the same geographical area. In order to test the hypothesis of a common ancestor, consanguinity within and among the families was checked using three different approaches: reconstruction of genealogical trees, typing of blood markers, and surname analysis. The results of the three types of analyses strengthen the hypothesis that, in at least two out of the three families, the genetic defect determining the TTD/XP phenotype is identical by descent, as a consequence of remote inbreeding. This implies that if two mutations are responsible for the two diseases they are at linked loci or affect the same gene. PMID- 2308153 TI - An epidemiological and genetic study of congenital profound deafness in Tunisia (governorate of Nabeul). AB - An epidemiological and genetic study of profound deafness has been undertaken in the governorate of Nabeul in Tunisia. This paper deals with sensorineural deafness with no associated abnormalities. The prevalence was estimated to be 0.0007 and four clusters could be identified, two of which represent 51% and 34% respectively of the total number of cases. Segregation analysis performed in 29 pedigrees containing 415 subjects with 129 affected cases provided evidence for simple recessive inheritance with no sporadic cases. PMID- 2308154 TI - DNA markers near the cystic fibrosis locus: further analysis of the British population. AB - Genetic analysis of the CF locus in the British Caucasian population has been extended using six DNA probes detecting nine polymorphic loci. Data are presented on (1) diagnostic usefulness of probes, and (2) allele frequencies for each probe in this population. For the probes pXV2C and KM19 (those closest to the CF locus) allele frequencies are further subdivided into male and female derived chromosomes 7. The allele frequencies for both probes on non-CF bearing chromosomes 7, but not on CF carrying chromosomes 7, are substantially different in males and females. Combined haplotypes for pXV2C and KM19 show that, as has been observed in other northern European populations, almost 90% of CF chromosomes in this population carry the pXV2C/KM19, 1/2 (2.1 kb/6.6 kb) haplo type. PMID- 2308155 TI - The acrocallosal syndrome in a Turkish boy. AB - A 6 month old Turkish boy with the acrocallosal syndrome is reported. The patient, born to consanguineous, healthy parents, presented with macrocephaly, a prominent forehead, hypertelorism, polydactyly of the fingers and toes, severe motor and mental retardation, hypotonia, and absence of the corpus callosum. The mode of inheritance is discussed and our case is compared with previously reported cases of the syndrome. PMID- 2308156 TI - De novo deletion of Xp22.2-pter in a female with linear skin lesions of the face and neck, microphthalmia, and anterior chamber eye anomalies. AB - A female infant is described with an unusual combination of eye and skin findings. Raw linear skin lesions on the face and neck were present at birth, healing to leave pigmented streaks. In addition she had left sided microphthalmia and bilateral sclerocornea. Chromosome analysis showed a terminal deletion of the short arm of the X chromosome (Xp22.2--pter). Clinical findings were similar to three previously described children with translocations involving Xp22.3. The condition probably represents a new syndrome distinct from incontinentia pigmenti and Goltz syndrome. PMID- 2308158 TI - Interstitial deletion of chromosome 4, del(4)(q12q21.1), in a child with multiple congenital abnormalities. PMID- 2308157 TI - Two 46,XX,t(X;Y) females with linear skin defects and congenital microphthalmia: a new syndrome at Xp22.3. AB - We describe two females with de novo X;Y translocations, who presented at birth with irregular linear areas of erythematous skin hypoplasia involving the head and neck, along with eye findings that included microphthalmia, corneal opacities, and orbital cysts. The features in these children are similar to but distinct from those seen in females with Goltz syndrome and incontinentia pigmenti. Cytogenetic analysis has shown the X chromosome breakpoint in both females to be at Xp22.3. We suggest that this syndrome is the result of a deletion or disruption of DNA sequences in the region of Xp22.3. PMID- 2308159 TI - A consortium approach to molecular genetic services. Scottish Molecular Genetics Consortium. AB - The four Scottish university medical genetics centres formed a consortium in 1985 to provide a DNA based service in prenatal diagnosis, carrier detection, and predictive testing for a range of Mendelian disorders. Each centre took sole responsibility for laboratory analyses of an assigned set of disorders, while families continued to be investigated and patients counselled within their own areas. DNA was extracted from relevant tissues in the centre most convenient to the family member and then dispatched to the appropriate laboratory for analysis. Results were interpreted and risks assessed by discussion between laboratory staff and the clinical geneticist in charge of the case. In the first three years of the consortium 92 prenatal diagnoses or exclusion tests were carried out, the majority being for cystic fibrosis (35), Duchenne muscular dystrophy (21), and Huntington's disease (11). Carrier testing was carried out in 271 X linked recessive disorders, the most common indications being Duchenne and Becker muscular dystrophies (198) and haemophilias A and B (48). Predictive testing was attempted in 41 consultants at risk for Huntington's disease, 37 at risk for myotonic dystrophy, and 32 at risk for developing adult polycystic kidney disease. The total of all carrier tests, including those for autosomal recessives, was 543. A consortium or supraregional approach to molecular genetics services has a number of advantages. Constituent laboratories need hold only those probes and enzymes relevant to their assigned disorders and can gain maximum experience with these systems. Scattered families may often be linked into single kinships, thus allowing rapid confirmation of diagnosis when an urgent request is made for a prenatal diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308160 TI - Crystallization of serine carboxypeptidases. AB - Crystallization of three different serine carboxypeptidases has been achieved by the method of hanging-drop vapor diffusion. Serine carboxypeptidases II from wheat bran and malted barley crystallize isomorphously from polyethylene glycol solutions at room temperature (pH 4 to 7) in space group P4(1)2(1)2 or enantiomorph with cell dimensions of a = b = 98.2 A and c = 209.5 A. The crystals diffract to about 2.3 A resolution using rotating-anode X-ray generators. Assuming a dimer of Mr 120,000 in the asymmetric unit, Vm = 2.1 A3/dalton. These crystals appear suitable for structural studies. A genetically engineered serine carboxypeptidase from yeast, which lacks three of four glycosylation sites present in the wild-type, has also been crystallized by vapor diffusion against methylpentanediol at 4 degrees C, pH 6.4 to 8.0. PMID- 2308161 TI - Generation of skeletal, smooth and low molecular weight non-muscle tropomyosin isoforms from the chicken tropomyosin 1 gene. AB - We have determined the organization of the chicken tropomyosin 1 gene by sequencing the cloned genomic DNA. The single-copy gene spans approximately 11,000 bases and includes 12 exons. Comparison of cDNA and genomic sequences demonstrates that three tissue-specific tropomyosins are encoded by the gene: a 284 amino acid skeletal muscle beta-tropomyosin, a 284 amino acid smooth muscle tropomyosin, and a 248 amino acid non-muscle (fibroblast) beta-tropomyosin. Skeletal and smooth muscle transcripts use the same putative promoter and transcription initiation site. However, they are alternatively spliced to generate mRNAs that differ in the region giving rise to amino acids 188 to 213 and 258 through the poly(A) site. The fibroblast transcript uses a promoter, initiation site and first exon that is distinct from that used for both the smooth and the skeletal muscle transcripts. However, beyond the first exon the fibroblast transcript undergoes splicing and polyadenylation that is identical with the smooth muscle transcript. PMID- 2308162 TI - Molecular analysis of human acatalasemia. Identification of a splicing mutation. AB - To search for the molecular defect of Japanese-type acatalasemia, we cloned the mutant catalase gene from a person with this deficiency. The nucleotide sequence of the mutant gene was determined for all exons, exon/intron junctions, and 5' and 3' flanking regions, and the findings were compared with the sequence from the normal gene. Seven base differences were found between the two genes. Among them, a G to A substitution at the fifth position of intron 4 (a splicing mutation) seemed most likely to be responsible for the defective catalase synthesis in the subject. To obtain suggestive evidence, we constructed chimeric genes that contained a segment of either the normal or mutant catalase gene, encompassing a 3' part of exon 4, the entire intron 4 and a 5' portion of exon 5, within the third exon of the human alpha-globin gene. When this chimeric gene construct was introduced into simian virus 40-transformed simian cells (COS-7), the transcript of the normal catalase/alpha-globin chimeric gene was spliced correctly, as revealed by Northern blotting and RNase mapping techniques. In contrast, the splicing of the mutant chimeric pre-mRNA occurred between the 5' donor site of the preceding intron and the 3' acceptor site of the intron containing the substitution, thereby skipping one entire exon sequence. Thus, the G to A transition at the fifth position of intron 4 of the catalase gene indeed severely limits the correct splicing of the RNA product. The same splice site mutation was found in the genomic DNA of another acatalasemic individual from an unrelated family. We suggest that this base substitution is the causal mutation of these cases of Japanese-type acatalasemia. PMID- 2308163 TI - Heterogenic mRNAs with an identical protein-coding region of the human embryonic myosin alkali light chain in skeletal muscle cells. AB - The formation of human myotubes in culture is accompanied by the induction of developmentally regulated, muscle-specific genes. We have studied the expression of human myosin light chain proteins and mRNAs during myogenesis in culture, in particular the skeletal embryonic myosin light chain 1 (MC1emb), which is indistinguishable from MLC1 of adult atrial cardiac muscle (MLC1A) as has been shown for rodent and bovine MLC1emb. We have identified distinct MLC1emb/MLC1A mRNAs in cultured human skeletal muscle cells that differ in their 5' and 3' untranslated regions but contain identical protein-coding regions. The alternative 3' untranslated region is detectable also in RNA of human atria. The different MLC1emb RNAs are likely to be encoded by one gene. It appears that the two MLC1emb 5' untranslated regions of the human gene are specific for man. In the mouse, only one 5' untranslated region of the MLC1emb gene has been detected. PMID- 2308164 TI - Stereochemistry of carbon monoxide binding to normal human adult and Cowtown haemoglobins. AB - The structures of carbonmonoxyhaemoglobins A and Cowtown (His146 beta----Leu) have been refined at 2.2 A (1 A = 0.1 nm) and 2.3 A resolution, respectively. The least squares fit to the Fe-C-O line makes an angle to the haem normal of about 6 degrees. The Fe-C-O group is bent from linearity by about 7 degrees. The porphyrins in the CO liganded haemoglobins are ruffled. This deformation of the haem and the distortion of the Fe-C-O group may explain the low CO affinity of haemoglobin. The electron density for the C-terminal residues is low but sufficient to distinguish the histidyl and leucyl residues clearly. The similarity between these two structures, apart from 146 beta, means that the reduced alkaline Bohr effect is due solely to the replacement of histidine by a leucine. PMID- 2308165 TI - Conserved sequences flank variable tandem repeats in two alleles of the G surface protein of Paramecium primaurelia. AB - We describe the cloning and the sequencing of a macronuclear DNA fragment of Paramecium primaurelia, strain 168, encompassing the entire coding region of the 168G surface protein gene. Comparison of its nucleotide and its deduced amino acid sequences to those of the allelic surface protein 156G, previously described, reveals the rigorous conservation of a highly periodic structure. This structure is based on the presence of 37 periods of about 75 residues, each period containing eight cysteine residues. The differences between the two proteins are clustered in the central part of the sequence, which is itself made of quasi-identical tandem repeats. We propose that these repeats constitute the domain exposed on the surface of the cells and present the characteristics of concerted evolution. PMID- 2308166 TI - Deletion-tolerance and trans-splicing of the bacteriophage T4 td intron. Analysis of the P6-L6a region. AB - Non-directed mutagenesis and phylogenetic comparison suggest that certain elements of the bacteriophage T4 td group Ia intron are dispensable to self splicing. The L6-P6a-L6a region was identified as a potential non-essential element, and was removed by sequential deletions extending from the L6a loop toward the P6 pairing. Assays for splicing indicate that as long as the P6 pairing is maintained, the 1016 nucleotide td intron can be reduced to less than 250 nucleotides while maintaining function in vivo and in vitro. The P6 pairing appears to be essential for splicing while P6a is not. In addition, a spontaneous pseudorevertant of a splicing-defective deletion was isolated and shown to result from a single nucleotide change in the predicted L6a loop. This genetic suppressor mimics the ability of Mg2+ to reverse the phenotype of the deletion, suggesting that function is restored by structural stabilization of P6. The tolerance of this region to deletion prompted us to split the ribozyme core in L6a, to generate precursors that might function in trans. Indeed, the two half molecules do associate to form a bimolecular complex that yields accurately ligated exons both in vitro and in vivo. The biological implications of these results, as well as the usefulness of trans-splicing for generating unprocessed precursors in vitro are discussed. PMID- 2308167 TI - D-periodic assemblies of type I procollagen. AB - The solubility limit of purified chick type I procollagen, incubated at 37 degrees C in phosphate-buffered saline, was found to be in the range 1 to 1.5 mg/ml. At higher concentrations large aggregates formed. These comprised: (1) D periodic assemblies; (2) narrow filaments with no apparent periodicity; and (3) segment-long-spacing-like aggregates. The D-periodic assemblies, which predominated at high concentrations, were separated from the other types of aggregate and found to be ribbon-like. Ribbons were uniform in thickness (approximately 8 nm) and up to 1 micron wide. Staining patterns showed features similar to those in native-type collagen fibrils. Immunolabelling indicated that the carboxyl-terminal propeptide domains were close to the carboxyl-terminal gap overlap junction, and that the amino-terminal propeptide domains were folded over into the amino-terminal side of the overlap zone. Both propeptide domains appeared to be located on the surface of the assemblies. These observations show that intact propeptide domains hinder, but do not prevent, the formation of D periodic assemblies. The presence of the propeptide domains on the surface of a growing assembly could restrict its lateral growth and limit its final thickness. PMID- 2308168 TI - SIRIUS. An automated method for the analysis of the preferred packing arrangements between protein groups. AB - Automated methods have been developed to determine the preferred packing arrangement between interacting protein groups. A suite of FORTRAN programs, SIRIUS, is described for calculating and analysing the geometries of interacting protein groups using crystallographically derived atomic co-ordinates. The programs involved in calculating the geometries search for interacting pairs of protein groups using a distance criterion, and then calculate the spatial disposition and orientation of the pair. The second set of programs is devoted to analysis. This involves calculating the observed and expected distributions of the angles and assessing the statistical significance of the difference between the two. A database of the geometries of the 400 combinations of side-chain to side-chain interaction has been created. The approach used in analysing the geometrical information is illustrated here with specific examples of interactions between side-chains, peptide groups and particular types of atom. At the side-chain level, an analysis of aromatic-amino interactions, and the interactions of peptide carbonyl groups with arginine residues is presented. At the atomic level the analyses include the spatial disposition of oxygen atoms around tyrosine residues, and the frequency and type of contact between carbon, nitrogen and oxygen atoms. This information is currently being applied to the modelling of protein interactions. PMID- 2308169 TI - Crystal structure of plastocyanin from a green alga, Enteromorpha prolifera. AB - The crystal structure of the Cu-containing protein plastocyanin (Mr 10,500) from the green alga Enteromorpha prolifera has been solved by molecular replacement. The structure was refined by constrained-restrained and restrained reciprocal space least-squares techniques. The refined model includes 111 solvent sites. There is evidence for alternate conformers at eight residues. The residual is 0.12 for a data set comprising 74% of all observations accessible at 1.85 A resolution. The beta-sandwich structure of the algal plastocyanin is effectively the same as that of poplar leaf (Populus nigra var. italica) plastocyanin determined at 1.6 A resolution. The sequence homology between the two proteins is 56%. Differences between the contacts in the hydrophobic core create some significant (0.5 to 1.2 A) movements of the polypeptide backbone, resulting in small differences between the orientations and separations of corresponding beta strands. These differences are most pronounced at the end of the molecule remote from the Cu site. The largest structural differences occur in the single non-beta strand, which includes the sole turn of helix in the molecule: two of the residues in a prominent kink of the poplar plastocyanin backbone are missing from the algal plastocyanin sequence, and there is a significant change in the position of the helical segment in relation to the beta-sandwich. Several other small but significant structural differences can be correlated with intermolecular contacts in the crystals. An intramolecular carboxyl-carboxylate hydrogen bond in the algal plastocyanin may be associated with an unusually high pKa. The dimensions of the Cu site in the two plastocyanins are, within the limits of precision, identical. PMID- 2308170 TI - Prenatal detection of simian crease. AB - We present the prenatal detection of a simian crease (transverse palmar line) in seven fetuses. Three fetuses had trisomy 21, four had normal chromosomes but another anomaly (meningomyelocele, thanatophoric dysplasia, achondroplasia [2]). The technique used and normal anatomy are described. PMID- 2308171 TI - Thalidomide's back in the news, but in more favorable circumstances. PMID- 2308172 TI - Research focuses on immunosuppressive effect, unknown teratogenic mechanism of thalidomide. PMID- 2308173 TI - Investigational new drug (US) 'orphan' trials now use thalidomide from two sources. PMID- 2308174 TI - From the Food and Drug Administration. PMID- 2308175 TI - Cesarean section guidelines: the Maryland experience. PMID- 2308176 TI - Surgeon volume vs hospital volume: which matters more? PMID- 2308177 TI - More yellow ovaries. PMID- 2308178 TI - Tumor necrosis factor in sepsis. PMID- 2308179 TI - Public health policy on varicella infection. PMID- 2308180 TI - Intravenous substance abuse and a presacral mass. PMID- 2308181 TI - Spinal anesthesia and mini-dose heparin. PMID- 2308182 TI - Tryptophan-associated eosinophilic connective-tissue disease. A new clinical entity? AB - Seven patients who developed a syndrome of eosinophilia, connective-tissue disease, and cutaneous abnormalities while ingesting tryptophan were examined. Other clinical manifestations commonly seen were pulmonary symptoms, fever, lymphadenopathy, and the development of myopathy. Laboratory features included mild elevations of aldolase and lactate dehydrogenase levels, with essentially normal creatine kinase levels, erythrocyte sedimentation rates, and C-reactive protein levels. Biopsy findings included features of scleroderma, small-vessel vasculitis, fasciitis, and myopathy. Discontinuation of tryptophan administration and implementation of corticosteroid therapy were of some benefit in relieving the intense myalgias and cutaneous findings that developed. Although temporally related to tryptophan ingestion, it is unclear whether this substance, a metabolite, or a contaminant were causal. We speculate that the pathogenesis of this syndrome may relate to abnormalities in tryptophan metabolism. PMID- 2308183 TI - Farr's law applied to AIDS projections. AB - Farr's Law of Epidemics, first promulgated in 1840 and resurrected by Brownlee in the early 1900s, states that epidemics tend to rise and fall in a roughly symmetrical pattern that can be approximated by a normal bell-shaped curve. We applied this simple law to the reported annual incidence of cases of acquired immunodeficiency syndrome in the United States from 1982 through 1987. The 6 years of incidence data closely fit a normal distribution that crests in late 1988 and then declines to a low point by the mid-1990s. The projected size of the epidemic falls in the range of 200 000 cases. A continuing incidence of endemic cases can be expected to emerge, but we believe it will occur at a low level. PMID- 2308184 TI - Thyroidectomy for amiodarone-induced thyrotoxicosis. AB - Amiodarone hydrochloride, an iodine-rich drug used in the treatment of tachyarrhythmias, is responsible for the development of thyrotoxicosis in approximately 10% of patients who reside in areas of moderate iodine deficiency. Treatment of amiodarone-induced thyrotoxicosis is difficult since the drug has a prolonged half-life, cardiac decompensation due to underlying heart disease occurs often, and discontinuation of amiodarone therapy may not be possible. We report a patient with severe thyrotoxicosis who received amiodarone for 34 months. Prolonged treatment with methimazole, potassium perchlorate, iopanoic acid, and dexamethasone was unsuccessful in controlling the hyperthyroid state. A near-total thyroidectomy resulted in rapid amelioration of thyrotoxicosis. Since surgery results in rapid control of thyrotoxicosis and permits continued therapy with amiodarone, we suggest that near-total thyroidectomy warrants consideration as definitive treatment for resistant amiodarone-induced thyrotoxicosis. PMID- 2308185 TI - American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. AB - Selection of appropriate laboratory determinations will enable the clinician to diagnose thyroid dysfunction readily in the majority of patients. At the present time, estimation of free thyroxine and a "sensitive" thyrotropin assay are recommended as the principal laboratory tests for thyroid disease. A decrease in serum free thyroxine estimate and a raised level of serum thyrotropin confirm the diagnosis of hypothyroidism caused by thyroid gland failure. An increase in free thyroxine estimate combined with a serum sensitive thyrotropin level suppressed to less than 0.1 mU/L establishes the diagnosis of thyrotoxicosis. In sick patients, a normal or raised serum free thyroxine estimate together with a normal level of serum thyrotropin suggests that the patient has neither hypothyroidism nor thyrotoxicosis. Patients with severe illnesses, generally in the intensive care unit, and those treated with certain drugs, as well as individuals with unusual thyroid disorders, may present with confusing laboratory findings. An understanding of the regulation of the thyroid hormone system and/or judicious consultation with an endocrinologist should enable the clinician to diagnose thyroid disease, if present, in such patients. PMID- 2308186 TI - Projecting the incidence of AIDS. PMID- 2308187 TI - The future course of AIDS in the United States. PMID- 2308188 TI - From the Office of the General Counsel. Practice parameters and the malpractice liability of physicians. PMID- 2308189 TI - Controversy continues as experts ponder zidovudine's role in early HIV infection. PMID- 2308190 TI - From the Agency for Health Care Policy and Research. PMID- 2308191 TI - Community-based medical education in the Philippines. PMID- 2308192 TI - Doing a combined residency. PMID- 2308193 TI - Fifty hours for the poor. PMID- 2308194 TI - History and examination should precede tests. PMID- 2308195 TI - Potassium iodide stockpile for nuclear accidents. PMID- 2308196 TI - Pimping. PMID- 2308197 TI - Ibuprofen and aspirin in acute rheumatic fever. PMID- 2308198 TI - Comparative longevity of Christian Scientists. PMID- 2308199 TI - Prolonged zidovudine therapy: confounded by Pneumocystis carinii prophylaxis? PMID- 2308200 TI - JAMA's covers: if Van Cleven rates 13, is it all Rembrandts for 50 years? PMID- 2308201 TI - Potomac fever or White House wisdom? PMID- 2308202 TI - A piece of my mind. Mysterium tremendum et fascinans. PMID- 2308203 TI - Risk of seizures and encephalopathy after immunization with the diphtheria tetanus-pertussis vaccine. AB - We evaluated the risks of seizures and other neurological events following diphtheria-tetanus-pertussis (DTP) immunization for 38,171 Tennessee Medicaid children who received 107,154 DTP immunizations in their first 3 years of life. There were 2 children with encephalitis; both had disease onset more than 2 weeks following DTP immunization. There were 277 children who had febrile seizures, 42 with afebrile seizures, and 37 with seizures associated with other acute neurological illness (acute symptomatic). The risk of febrile seizures in the 0 to 3 days following DTP immunization (n = 6) was 1.5 (95% confidence interval, 0.6 to 3.3) times that of the control period 30 or more days following DTP immunization. There was no evidence that in the 0 to 3 days following DTP immunization the risk of afebrile seizures (n = 1) or acute symptomatic seizures (n = 0) was increased. No child who was previously normal without a prior history of seizures had a seizure in the 0 to 3 days following immunization that marked the onset of either epilepsy or other neurological or developmental abnormality. PMID- 2308204 TI - Treatment of resistant herpes simplex virus with continuous-infusion acyclovir. AB - Two patients with acquired immunodeficiency syndrome who developed severe ulcerative proctitis caused by herpes simplex virus type 2 that was resistant to acyclovir were successfully treated with 6 weeks of high-dose, continuous infusion acyclovir sodium (1.5 to 2.0 mg/kg per hour). Viruses cultured from the lesions were resistant to acyclovir in vitro after the patients had received prolonged therapy with oral and intravenous acyclovir in traditional divided doses. Investigation into the mechanism of the acyclovir resistance revealed changes in the thymidine-kinase activity of both isolates. This viral enzyme phosphorylates acyclovir and is necessary for drug activation. The first patient's isolate was deficient of all thymidine-kinase activity, while the second patient's isolate had a thymidine kinase with altered substrate specificity for acyclovir. The continuous infusion was safe, well tolerated, and done in an outpatient setting with weekly clinic visits and monitoring of creatinine and acyclovir levels. PMID- 2308205 TI - Computed tomography and magnetic resonance imaging comparisons in boxers. AB - The efficacy of computed tomography (CT) and magnetic resonance imaging (MRI) in identifying traumatic injuries of the brain was compared in a referred population of 21 amateur and professional boxers. Three boxers displayed CT scans with equivocal findings that were verified as artifacts by MRI. Eleven boxers had both CT and MRI scans with normal findings, and 7 boxers had both CT and MRI scans with abnormal findings. There were no instances where abnormalities demonstrated on CT scanning were not detected by MRI. However, some abnormalities detected on MRI were not detected on CT scans. These included a subdural hematoma, white matter changes, and a focal contusion. Magnetic resonance imaging appears to be the neuroradiodiagnostic test of choice compared with CT. PMID- 2308206 TI - 'Pertussis vaccine encephalopathy': it is time to recognize it as the myth that it is. PMID- 2308207 TI - [A phase 2 study of recombinant interleukin 2 (S-6820) for head and neck cancer]. AB - To evaluate the clinical efficacy and safety of a recombinant interleukin-2 (S 6820) therapy for head and neck cancer, a phase 2 study was conducted in a cooperative endeavor that has involved 23 institutions throughout Japan. Of the 81 patients in this study, 46 were eligible for an evaluation of the efficacy of this therapy. Two patients achieved a complete response (CR), and 4 patients achieved a partial response (PR). The overall efficacy rate was 13.0% (6/46), and good responses were obtained following a local injection either intratumorally or about the tumor. In contrast, a good result was not obtained from systemic administrations. WBC and lymphocyte counts in the peripheral blood increased and NK activity and LAK cells were seen to develop after treatment. Side effects were observed in 70.9% of 55 evaluable patients. These effects included fever (61.8%) or general fatigue (14.5%). In the laboratory findings, abnormalities such as eosinophilia were noted in 65.5% of patients. PMID- 2308208 TI - [The relation of the DNA ploidy pattern to lymphatic permeation in pure-type diffuse infiltrative carcinomas of the stomach]. AB - Lymphatic permeation (ly) is considered an important prognostic factor, even in the case of a diffuse infiltrative carcinoma (DICA) of the stomach, which generally has the poorest prognosis among the various types of gastric carcinomas. Our previous study has revealed that the ly in DICA is strongly related to the histological type of carcinoma that infiltrates the tumor tissue: the "mixed type", i.e., a type that includes tubular/trabeculoacinar element in 10% or more of the tumor tissue presents a significantly higher incidence of ly than the "pure type", i.e., a type that consists almost exclusively of anaplastic/mucocellular carcinoma. However, even in the "pure type" cases, some show a high ly incidence. To clarify this discrepancy, the DNA ploidy pattern in the "pure type" DICA was investigated, since the DNA ploidy has been reported to correlate well with the invasiveness or the metastatic tendency of the tumor. Although most of the cases (70%) showed a heteroploidy, such an incidence was significantly higher in the cases with a marked ly (86%) than in the cases without ly. (60%). As a result, we have concluded that in cases of a DICA, the lymphatic permeation (ly) is remarkably influenced not only by the histological type seen but also by the DNA ploidy pattern of the carcinoma. PMID- 2308209 TI - [Incidence of multiple myeloma in Nagasaki City, with special reference to those subjected to atomic bomb exposure]. AB - In order to observe the incidence of multiple myeloma in the population of Nagasaki City from 1973 to 1982, and to assess any influence caused by A-bomb exposure, 85 cases of myeloma have been collected and analysed. Informatively, 48 cases of this number were A-bomb survivors. Among the middle-aged cases, the crude incidence rates of myeloma in the exposed group were found to be higher than those in the non-exposed group. Further, the relative risk of myeloma was higher in A-bomb survivors and this tendency become more pronounced in the those who were within 2 km of the epicenter of the blast. The age-adjusted relative risk in male and female A-bomb survivors was 1.59 and 1.68 respectively, but no significant differences were noted. PMID- 2308210 TI - [Infarctions in fibroadenomas of the breast during pregnancy--a case report and a review of the literature]. AB - Described is a case of infarctions in fibroadenomas of the breast that occurred during pregnancy, with a review of the pertinent literature and a brief discussion on the difficulty of achieving a cytologic diagnosis. A 24-year-old female presented tender lumps that increased in size in her breast during the 7 months of her pregnancy. A subsequent cytologic examination revealed many typical cells with clustered nude nuclei. The cytologic diagnosis indicated a Group V, poorly differentiated adenocarcinoma. Following delivery of her infant, the lumps were excised. Microscopic examination revealed extensive infarcted fibroadenomas with lactational changes. PMID- 2308212 TI - [A case of retroperitoneal mucinous cystadenocarcinoma]. AB - We reported is the histogenesis of a case of a primary retroperitoneal cystadenocarcinoma that was resected surgically in a 42-year-old woman who was admitted to hospital for SLE. On echographic examination, she was found to have a right abdominal tumor and underwent an operation for the complete removal of an abdominal tumor located in the right retroperitoneal cavity. A histological examination of the tumor revealed it to be compatible with a mucinous cystadenocarcinoma of the ovary. Only four cases of a primary retroperitoneal mucinous cystadenocarcinoma have been reported in the literature. This rare lesion was studied histopathologically and its histogenesis is discussed. PMID- 2308213 TI - [Treatment of malignant lymphoma of the small intestine in aged patients over 70]. AB - Case histories of three elderly patients with a malignant lymphoma of the small intestine are described. Case No. 1 involved a 80-year-old male with a diffuse malignant lymphoma of medium size that was associated with a jejunal perforation. On the 64th day after surgery, he died of heart failure during the course of chemotherapy. Case No. 2 was a 76-year-old male with a diffuse malignant lymphoma of medium size in the ileocecum. He left hospital after surgery had relieved his symptoms, although 8 months after he developed active pulmonary tuberculosis during the course of chemotherapy. Case No. 3 involved a 76-year-old female with a diffuse malignant lymphoma of the mixed cell type in the terminal ileum. She died of heart failure complicated by a pulmonary disease on the 36th postoperative day. The therapeutic results of treating the malignant lymphoma in these 3 aged patients were all unfavorable. Thus, it is felt that special care should be taken in treating aged patients with this kind of disease. PMID- 2308211 TI - [A primary adenosquamous carcinoma of the stomach difficult to differentiate from gastric ulcer]. AB - The case involves a 57-year-old male who complained of an upper abdominal pain when hungry. An adenosquamous carcinoma of the stomach, however, is rare, and to make such an initial preoperative diagnosis endoscopically from a biopsied specimen is extremely unusual. Thus, as can be expected, on first examination, that the patient had a grade II adenosquamous carcinoma of the stomach was not determined. Two months later, however, on second diagnosis, a primary adenosquamous carcinoma of the stomach in the interior part of the angle region was made after an endoscopic study of a biopsied specimen. PMID- 2308214 TI - [An aggressive angiomyxoma of the vulva]. AB - A case of an aggressive angiomyxoma of the vulva in a 38-year-old lady is reported. The tumor was gelatinous and 12 x 8 x 7 cm in size. Histologically, spindle or stellate-shaped tumor cells and blood vessels were found distributed in a myxoid stroma. It was found that the tumor cells were immunoreactive to vimentin but negative to desmin and smooth muscle specific actin. Ultrastructurally the tumor cells had an intercellular junction, an abundant, rough endemic reticulum, and intracytoplasmic filaments, but no focal densities of the filaments and the basal lamina. These findings have revealed that this tumor consisted of myofibroblastic cells resembling fibroblasts rather than myofibroblasts. PMID- 2308215 TI - [Radiation-induced malignant skin tumors in the hands of five doctors]. AB - Radiation-induced malignant skin tumors in the hands in 3 surgeons, one physician, and one dentist are reported. The latent period of the irradiation ranged between 16 years and 34 years. Clinically, small keratotic lesions were seen in 4 doctors and a large tumor the remaining doctor. On histological examination, one of the tumors was a squamous cell carcinoma, 3 were carcinomas in situ, and the fifth was a basal cell carcinoma with a squamous cell carcinoma. While the occupational hazard of developing malignant skin tumors following irradiation have decreased recently, this paper emphasizes precautions should be taken when diagnosing and caring for cancer patients. PMID- 2308216 TI - [Evaluation of agar media for growth of Campylobacter pylori]. AB - The supporting ability for the growth of Campylobacter pylori was tested on various agar plates. C. pylori grew on media supplemented with blood, serum or egg-yolk, and it showed good growth on Mueller Hinton agar with horse blood, and on brain-heart infusion agar with yeast extract and horse blood. The organism grew moderately on Mueller Hinton agar, but could not grow on the other unsupplemented media. Mueller Hinton medium may be of use as a proper base of blood agar for growth of C. pylori. Egg-yolk may be substituted as a low-priced enrichment material for blood. PMID- 2308217 TI - [Correlation between intracellular alkaline phosphatase activities and incidence of toxic granules in neutrophilia]. AB - We examined the intracellular alkaline phosphatase (NIAP) activities in peripheral neutrophils in 15 healthy subjects and 15 patients with inflammatory diseases, and compared them with the percentages of neutrophils with cytoplasmic toxic granules (NTG), which is thought to be induced by infection. NIAP activities were markedly increased in patients and significantly correlated with the percentages of NTG. These data indicate that measurement of NIAP activity is useful for the diagnosis of infections and/or inflammatory diseases. PMID- 2308218 TI - [In vitro chemosensitivity test: succinate dehydrogenase inhibition (SDI) test]. AB - The succinate dehydrogenase inhibition (SDI) test was used for determining chemosensitivity of various human tumors. This test was based on the correlation between the cellular succinate dehydrogenase activity as determined by 3-(4,5 dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT), and cell viability. The chemosensitivity varied in the tissue. Some factors are involved in the chemosensitivity, that is origin of a tumor, tissue differentiation and tissue DNA synthetic activity. This test is a convenient method for clinical use and provides important information about chemosensitivity. PMID- 2308219 TI - [Steroid hormone receptors in breast cancer]. AB - The significance of hormone receptor (estrogen(ER)- and progesterone receptor (PgR) assay was described with special reference to the treatment of advanced and early breast cancer. Fifty to sixty percent of ER-positive breast cancer responds to endocrine treatment, while only about 10% of ER-negative cancer do. Advanced breast cancer patients with ER-positive tumors survive longer than those with ER negative tumors, mainly because of better response to therapy. The clinical benefit of assaying the hormone receptors in primary breast cancer was discussed, particularly concerning with the relapse-free and overall survivals of the patients after primary operation. The findings suggest the possibility of selecting operable breast cancer patients for the most appropriate adjuvant using ER and PgR. PMID- 2308220 TI - [Laboratory tests on cancer]. AB - Extensive research on "Cancer" have been undertaken using inovative techniques. However, the knowledge and techniques gained from this research has not fully been introduced into clinical laboratories, except for analysis of tumor markers in the blood or in the cells and some oncogenes. In this symposium, we show some possibilities in transferring the new knowledge and techniques from research laboratories to clinical laboratories. These lectures will inspire us to introduce more tests on "Cancer" into the laboratories. PMID- 2308221 TI - [Basic and clinical aspects of tumor markers--with special reference to CEA]. AB - Recent advances in carcinoembryonic antigen (CEA) research were reviewed. The primary structure of CEA peptide, mode of membrane anchoring of CEA, heterogeneity of carbohydrate chains, which seemed to be a main cause of the variations in CEA titers of patient's sera, and a newly established monoclonal radioimmunoassay system that revealed very homogeneous reactions with all CEA preparations and improved results on clinical applications were described. Furthermore, a recent finding that CEA is produced by normal colon mucosa as actively as by cancerous tissue was discussed. PMID- 2308222 TI - [Laboratory tests on cancer--cytology]. AB - A comparative study was performed on needle aspiration cytology and the histological grading of 34 cases of small liver cancers. According to the Edmondson-Steiner's classification, 9 of the 34 cases were Grade I, 10 cases were a mixture of Grades I and II and 15 were Grade II or a mixture of Grades II and III or Grades I, II and III. The group consisting of Grade II and mixtures of Grades II and III or Grades I, Ii and III were diagnosed by needle aspiration cytology using cytological criteria described previously, but cases consisting of Grade I and mixtures of Grades I and II were very difficult to diagnose because of the relative lack of cellular atypia, and the diagnostic accuracy in this group was low. Retrospectively, ceLlularity, cellular architecture and the nuclear-cytoplasmic ratio were the most valuable cytological findings in the cases of Edmondson-Steiner's Grade I and the mixture of Grades I and II. In addition, some cases of small liver cancers had characteristically large lipid vacuoles which resembled a signet ring cell. Imprint cytology of neuroblastomas is a rapid diagnostic test which is very useful for differential diagnosis of neuroblastoma from other childhood solid tumors. Recently, flow cytometric DNA analysis and the N-myc oncogene have been proposed as important factors in the estimation of the prognosis of neuroblastomas. Three of fore patients with aneuploid DNA under the age of 1.5 years at diagnosis survive, while five of eight patients with diploid DNA over the age of 1.5 years at diagnosis died during a 12 to 120 month follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308223 TI - [Role of HPLC in separation analysis in laboratory medicine]. AB - The principle, theory and analytical application of high performance liquid chromatography (HPLC) in laboratory medicine was described. The importance of separation analysis was focussed with respect to accuracy, precision, short-time assay and easy operation. The pretreatment of samples such as deproteinization was also important for the accurate results and the analysis of plasma catecholamines and hemoglobin A1c were described as examples with use of column switching technique, step-wise separation, gradient elution method on TSK gels. We demonstrated the results of plasma free amino acids, gamma-carboxyglutamic acid and catecholamines in the aged which had been engaged in our laboratory as routine test and application with use of HPLC connected to chemiluminescent analyzer. Catecholamine analysis showed the importance of reproducibility and recovery. The reproducibility was within 2% as CV and 93-96% as recovery %. In the case of plasma free amino acid analysis, ASP, GLU, ALA showed decreases in the aged, but CYS did increase with age. Concerning about the drug monitoring of cyclospolin A in the infant whole blood after liver transplantation, the serum levels of cyclospolin A showed the lower concentration than whole blood. The extraction of cyclospolin A was required after deproteinization of whole blood as pretreatment. PMID- 2308224 TI - [Clinical application of fast protein liquid chromatography (FPLC) system]. AB - FPLC system is a high-performance liquid chromatography system, designed specifically for separation of proteins, peptides and polynucleotides. Many kinds of column have been prepared, including Mono Q, Mono S, Mono P, Superose, etc. for ion exchange chromatography, chromatofocussing, gel filtration, hydrophobic chromatography, reversed phase chromatography and affinity chromatography. It is a fast and simple system for separation of proteins in various body fluids, particularly plasma, urine and cerebrospinal fluid. PMID- 2308225 TI - [Clinical laboratory application of HPLC]. AB - In clinical laboratory tests, high performance liquid chromatography (HPLC) has been widely used because of good reproducibility of data and easy automatization. In this workshop, separation of IgG and albumin in commercially available IgG preparation and determination of blood theophylline and serum uric acid levels were conducted by the HPLC method. In separation of IgG and albumin, HPLC analysis was carried out within 10 minutes by using the high-performance gel filtration column (TSK gel G 3,000 SWXL). Blood theophylline was fully automatically determined by using the pretreated column to separate small molecular material before application of the analytical column. A good correlation of blood theophylline levels between HPLC and ordinary EIA method was observed. In determination of serum uric acid, pretreatment for deproteinization of samples by acid was done to measure exactly the whole blood uric acid content. Eluent was adjusted to pH 2.2 to increase affinity to ODS phase of the reversed column (TSK gel ODS-80 TM). There was a good correlation of values of uric acid between HPLC and uricase-catalase method. PMID- 2308226 TI - [Principal component analysis for microalbuminuria in patients with noninsulin dependent, maturity-onset diabetes mellitus]. AB - To determine causal mechanism(s) of microalbuminuria seen in patients with noninsulin-dependent diabetes mellitus (NIDDM), multivariate analysis (principal component analysis) was applied, using patient's age, disease length, fasting blood sugar level (FBS), hemoglobin A1c (HbA1c %), and presence of hypertension as variables. Albumin concentration in the first morning urine was determined by the Latex Photometric Immunoassay (LPIA), and was expressed as albumin index (AI, albumin excretion per gram creatinine). Sixty five cases who had been continuously negative or equivocal (+/-) for urinary protein by an usual paper test method were analysed. The result indicated these patients could be separated into following three groups. Group A (12 cases) showed the highest AI value, was characterized by longer disease length (greater than 10 yrs), and was thought to be in transitional phase into clinical proteinuric stage. Group B (7 cases) was characterized by poor diabetic control and normalization of the microalbuminuria might be possible by strict control measures. In Group C (14 cases), patients were in relatively early stage of the disease, and were under good diabetic control, but presence of hypertension was thought to be a provocative factor. PMID- 2308227 TI - [Influence of the anti-T4 autoantibody cross-reacting with T3 on serum T3 level determined by RIA]. AB - We encountered a patient who showed remarkably high binding capacities of both 125I-T4 and 125I-T3, which suggests the presence of antithyroid hormone autoantibody. However, the serum level of T3 in the patient was not abnormal. Study of the specificity of anti-thyroid autoantibody revealed that the antibody present in the patient was the anti T4 antibody, which cross-reacted with T3. In addition, the binding capacity of the T4 autoantibody with T3 was inhibited by T4. Endogenous T4 is always present when T3 is determined by radioimmunoassay. Our findings indicate that the normal T3 level in the patient was because endogenous T4 inhibited the autoantibody binding with T3. PMID- 2308228 TI - [Studies on transient hyperphosphatasemia]. AB - We found 39 cases of transient hyperphosphatasemia (TH) from 8 primary medical care institutions over a 2.5 year period, beginning in 1986, and 36 cases were available for this analysis. The maximum activity of serum alkaline phosphatase (ALP) was 318 K.A unit, and 16 cases showed 100 K.A unit or more. Ages of the TH cases were ranged from 8 to 92 months and average of 25.4 months. There were no seasonal fluctuation of the incidence. Although high fever was noticed in 21 cases (58%), and diarrhea and upper respiratory infections were observed in 9 cases (25%) each, no common characteristic features in underlying diseases or laboratory abnormalities were noticed. All of those clinical signs were returned to normal within one month, except for 3 cases in which we could not make follow up study. ALP levels were re-examined within one week in 14 cases (39%) but re examination was not requested in another 14 cases. ALP levels were returned to normal within one month but characteristic isoenzyme patterns for TH were detectable for up to 3 months from the onset. According to the investigation over 1.5 year period at Kumagaya pediatric hospital, 28 out of 7,287 samples (0.38%) were found to have TH. The mechanism to develop TH is not known, but sugar chain aberrations of ALP are more likely the cause, since viral infections were seen only a few occasions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308229 TI - [Interference in endotoxin and fungal polysaccharide assays from blood products and antimicrobial agents]. AB - A conventional chromogenic limulus test (CCLT, normal plasma value: less than 10 pg/ml) detects both of endotoxin and beta-1,3-glucan, while a chromogenic endotoxin-specific test (EST: less than 3 pg/ml) detects only endotoxin. Two sources of pseudo-positive result in CCLT and/or EST were studied; (1) factor G activating material found in blood products, which is indicative of fungal infections, and (2) interaction in diazo-coupling process of the tests by antibiotics or sulfonamides. CCLT and EST values obtained from 13 vials of blood products including human albumin, antithrombin III, and antihemophilic globulin were 284.6 +/- 284.6 pg/ml and 20.2 +/- 26.4 pg/ml (mean +/- SD), respectively. High CCLT values accompanied by low EST values indicate factor G-activating material in the blood products rather than endotoxin. Sample blanks of 42 plasma specimens obtained from 19 patients were 23.7 +/- 34.7 pg/ml by CCLT and 19.2 +/- 31.5 pg/ml by EST. All the patients were administered Sulfamethoxazole/Trimethoprim (SMX/TMP), Aztreonam (AZT), Ceftazidime (CAZ), Imipenem/Cilastatin (IPM/CS), or Silver sulfadiazine. SMX/TMP, AZT, CAZ, IPM/CS, and Cefmenoxime were demonstrated to react with the diazo-coupling reagents used in CCLT and EST, and to cause false-positive result in the tests. Thus the investigation of blood product and sample blank is required for the assay of endotoxins or fungal polysaccharides using CCLT and EST. PMID- 2308230 TI - [Clinical reference values for laboratory hematology tests calculated using the iterative truncation method with correction: Part 1. Reference values for erythrocyte count, hemoglobin quantity, hematocrit and other erythrocyte parameters including MCV, MCH, MCHC and RDW]. AB - Age and sex dependent differences in the clinical reference values for erythrocyte count (RBC), hemoglobin quantity (Hb), hematocrit (Ht) and other erythrocyte parameters including MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration) and RDW (red cell distribution width), were calculated by the iterative truncation method with correction (Usui's method) using the results from tests on 6,300 patients' specimens obtained at Kyoto University Hospital. For RBC, Hb and Ht, the data obtained from the individuals below 13 years old showed the normal or sometimes log-normal distribution, but adjustment by the Xn-type variable transformation was often necessary to obtain the normal distribution for the data taken from the populations containing individuals over the age of 14. For the clinical reference values of RBC, Hb and Ht, no sex difference was observed below the age of 12. The values for males were significantly higher than those of females in the age range 13-79, and the values showed no significant sex-dependent difference at ages above 80. In females, age-dependent change of values for RBC, Hb and Ht was less prominent than in males; especially the upper limit values for females were very stable for all ages. MCV and MCH gradually increased with age both in males and females, and the MCHC remained constant in all age populations of male and female. The reference value for RDW was generated by the percentile method instead of the iterative truncation method because of the strong deviation in the distribution pattern, and the RDW values showed a gradual increase with age in both males and females. PMID- 2308231 TI - Effects of Ca2+ blockers on the various types of stimuli-induced acetylcholine release from guinea pig ileum myenteric plexus. AB - In the present study, we investigated the effects of various Ca2+ blockers on the release of acetylcholine (ACh) induced by nicotine, electrical field stimulation (EFS) and high-K+. Cd2+ markedly depressed the ACh release due to these stimuli. Verapamil inhibited the nicotine-induced ACh release remarkably and the EFS- or the high-K(+)-induced ACh release to a lesser extent. Since the nicotine- and the EFS-induced ACh releases were inhibited by procaine, the local anesthetic property of verapamil likely contributes in part to the inhibition. Diltiazem abolished the nicotine-induced ACh release completely but did not affect the EFS induced release and significantly increased the high-K(+)-induced ACh release. These results suggest the absolute requirement for extracellular Ca2+ in the release of ACh induced by nicotine as well as EFS and high-K+. In addition, these stimuli may open the same Ca2+ channel to evoke ACh release. PMID- 2308232 TI - Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (8): Protective effect of pyridoxal-5'-phosphate against tobramycin nephrotoxicity. AB - We investigated the effect of pyridoxal-5'-phosphate (PALP) on tobramycin (TOB) induced nephrotoxicity in rats. Paper electrophoretic analysis showed that in the mixture of TOB and PALP, the spot corresponding to TOB alone almost disappeared and the spot associated with TOB overlapped with that associated with PALP, although the spots of TOB alone and PALP alone were observed as single spots on the cathode and anode sides, respectively. The overlapping of both compounds indicated that TOB could directly interact with PALP in vitro. In the assay of TOB binding to renal brush border membranes (BBMs), PALP significantly inhibited the binding of TOB to BBMs by interacting with TOB outside of BBMs vesicles. Intrarenal TOB levels in rats receiving TOB and PALP were lower than those in rats given TOB alone. Combination with PALP markedly suppressed the urinary protein content, urinary N-acetyl-beta-D-glucosaminidase activity and blood urea nitrogen content elevated by TOB, and also reduced the degree of TOB-induced renal tubular cell necrosis. These results indicate that PALP protects the rat kidneys from TOB-induced nephrotoxicity and that the protective effect of PALP may be due to the reduced intrarenal TOB concentration and less binding to TOB to BBMs induced by the interaction of PALP with TOB. PMID- 2308233 TI - Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine (3): Effects on crescentic-type anti-GBM nephritis in rats. AB - We investigated the antinephritic effects of TJ-8014, in comparison to dipyridamole, on crescentic-type anti-GBM nephritis in rats. When administration of test drugs was started from the heterologous phase (from the day after the anti-GBM serum injection), TJ-8014 at 2.0 g/kg/day, p.o., markedly inhibited the urinary protein excretion and elevations of plasma cholesterol and urea nitrogen levels as well as glomerular histopathological changes (i.e., crescent formation, adhesion and fibrinoid necrosis) throughout the 40-day observation period. TJ 8014 at 0.1 and 0.5 g/kg/day, p.o., and dipyridamole at 0.4 g/day, p.o., inhibited only the histopathological changes. When treatment was started from the autologous phase (from the 22nd day after the anti-GBM serum injection) after the disease had been established, only the high dose of 5.0 g/kg/day of TJ-8014, p.o., was effective in improving the histopathological changes of the established nephritis, as assessed on the 53rd day. The low doses of TJ-8014 and dipyridamole were ineffective. These results suggest that TJ-8014 may be a useful Japanese herbal medicine against rapidly progressive glomerulonephritis, which is characterized by severe glomerular lesions with the extensive formation of crescents. Furthermore, the mechanisms of action of this medicine will be discussed. PMID- 2308234 TI - S-adenosyl-L-methionine ameliorates reduced local cerebral glucose utilization following brain ischemia in the rat. AB - The average values of the local cerebral glucose utilization (LCGU) were approx. 35-110 mumols/100 g/min in various nuclei in the brain of sham-operated animals. The values, however, were decreased by 25-75% in all areas examined at 24 hr after 4-vessel occlusion (forebrain ischemia) for 0.5 hr. Particularly, the LCGU values in the forebrain nuclei such as the cerebral cortices and thalamus were severely reduced, while that in the nuclei in the midbrain and hindbrain such as the red nucleus, chochlear nucleus and vestibular nucleus were slightly reduced. In rats treated with S-adenosyl-L-methionine (SAM, 100 mg/kg, i.p.) every 1 hr for 6 times from the recirculation, however, the LCGU values were increased in all brain structures by 35-195% in the forebrain ischemic rat. A significant increase was observed in the cerebral neocortices, caudate-putamen, lateral septal nucleus, thalamic nuclei, substantia nigra, cerebellum and some other nuclei. In some forebrain structures whose LCGU were mildly reduced to approx. 60 70% by the ischemia, SAM recovered the LCGU to more than 90% of the value in the sham-operated group. Thus it was concluded that SAM ameliorated widely ischemia induced reduction of LCGU in the rat. PMID- 2308235 TI - Enhancement by L-methionine on the contractile response of uterine segments to acetylcholine and high KCl is mainly due to enhancement of Ca uptake. AB - Acetylcholine (ACh)- and high KCl-stimulated 45Ca uptake into rat uterine segments was inhibited by 3-deazaadenosine (3-DAA) plus homocysteine thiolactone (HCTL), and this inhibitory effect was attenuated by L-methionine (L-Met). Ca depleted Ringer solution in which uterine muscle had been incubated with L-Met did not enhance the contractile response of another uterine segment to ACh and high KCl in the presence of 3-DAA plus HCTL. These findings together with previous results suggest that the enhancing effect of L-Met on the contractile responses to ACh and high KCl is mainly due to an increase in Ca2+ uptake into the uterine muscle. PMID- 2308236 TI - Effects of orally administered human epidermal growth factor on natural and delayed healing of acetic acid-induced gastric ulcers in rats. AB - We examined the effects of orally administered human epidermal growth factor (hEGF) on healing of acetic acid-induced gastric ulcers in rats. hEGF, given twice daily at 30 and 100 micrograms/kg for 2 weeks or at 100 micrograms/kg for 4 weeks to rats with ulcers, had no effect on natural healing or the gastric secretion, delayed one caused by indomethacin. Oral hEGF had no effect on basal histamine-stimulated gastric secretion, and stomach weight. These results indicate that oral hEGF has no biological activity on the pathophysiology of the stomach. PMID- 2308237 TI - Nitroarginine inhibits endothelium-derived relaxation. AB - Effects of NG-nitro-L-arginine (NO2Arg), a guanidinonitro arginine derivative, on acetylcholine-induced relaxation of rabbit thoracic aorta ring preparation were studied. Relaxation by acetylcholine was inhibited by NO2Arg dose-dependently and the maximum relaxation with 10(2) microM NO2Arg was reduced to 10.1 +/- 4.3% (n = 5). L-arginine (10(2) microM) did not affect the acetylcholine-induced relaxation. Relaxation by glyceryltrinitrate or papaverine was not affected by NO2Arg. These results indicate that NO2Arg is a novel inhibitor of endothelium derived relaxation. PMID- 2308238 TI - Modification by L-NG-monomethyl arginine (L-NMMA) of the response to nerve stimulation in isolated dog mesenteric and cerebral arteries. AB - Treatment with L-NG-monomethyl arginine (L-NMMA) increased the vasoconstriction induced by adrenergic nerve stimulation in perfused dog mesenteric artery segments and suppressed the relaxant response to transmural nerve stimulation in dog cerebral artery strips, the effects of L-NMMA being reversed by L-arginine. The observed changes in nerve function may be associated with the inhibition of synthesis of nitric oxide. PMID- 2308239 TI - L-dopa methyl ester antagonizes competitively L-dopa-induced facilitation of noradrenaline release from rat hypothalamic slices. AB - In rat hypothalamic slices, antagonism by L-DOPA methyl ester and (-)-propranolol against L-DOPA-induced facilitation of endogenous noradrenaline (NA) release was characterized under the inhibition of dopadecarboxylase. L-DOPA at 10 nM to 1 microM facilitated the evoked NA release in a concentration-dependent manner. L DOPA methyl ester (3, 10 and 30 nM) progressively shifted the concentration release curve for L-DOPA to the right: Schild plots gave a straight line with a slope of 1.00 and pA2 was 8.9. This antagonistic action was not mimicked by L phenylalanine, a substrate for L-DOPA transport system. In contrast, 10 and 100 nM propranolol concentration-dependently reduced the maximal effect of L-DOPA without rightward shift of the concentration-release curve. L-DOPA methyl ester is a potent competitive antagonist for the action of L-DOPA, and the recognition site of L-DOPA differs from presynaptic beta-adrenoceptors. PMID- 2308241 TI - The Japanese Journal of Pharmacology. The 63rd annual meeting. March 25-28, 1990, Tokyo. Abstracts. PMID- 2308240 TI - A simple in vito cytotoxicity test using the MTT (3-(4,5)-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide) colorimetric assay: analysis of eugenol toxicity on dental pulp cells (RPC-C2A). AB - A simple colorimetric assay using MTT has been developed to monitor mammalian cell survival and proliferation in vitro. In this study we used a clonal fibroblastic cell line (RPC-C2A) from, rat incisal dental pulp to examine the effectiveness of the colorimetric assay to test for the toxicity of eugenol, which is frequently used to treat inflammed dental pulp. A technical problem encountered was the insolubility of MTT formazan, produced by the activity of mitochondria dehydrogenases. Dimethyl sulfoxide (DMSO) seemed to be the best solvent. Doses of eugenol causing a 50% inhibition in the colorimetric assay were calculated as 0.6 mM and 1 mM for cells in the growing phase and for cells at confluence, respectively. These values exist in the concentration range reported in the previous studies. Although the correlation between spectrophotometric absorbance and cell number was not completely linear, this method could be used effectively as a simple preliminary assay to test for the toxicity of dental drugs and materials. PMID- 2308242 TI - [The diagnostic value of cine-MR imaging in diseases of great vessels]. AB - The diagnostic value of cine magnetic resonance imaging (cine-MRI) was evaluated in 10 patients with disease of great vessels. The parameters necessary to decide the appropriate treatment, such as presence and extension of intimal flap, DeBakey type classification, identification of the entry, differentiation between true and false lumen, and between thrombosis and slow flow were demonstrated in all patients with dissecting aortic aneurysm. However, abdominal aortic branches could not be demonstrated enough by cine-MRI, therefore conventional AOG was necessary to choose the operative procedure in these cases. In patients with thoracic aortic aneurysm (TAA), cine-MRI was valuable in demonstrating both blood flow and thrombus in the lumen of aneurysm, and AOG was thought to be unnecessary in most cases. Cine-MRI is a promising new technique for the evaluation of diseases of great vessels. PMID- 2308243 TI - [Surgical management of open lung biopsy in Eizenmenger's syndrome]. AB - Three of 254 patients with Eizenmenger's syndrome had complications, namely bleeding during and after surgery of open lung biopsy. Histopathologic study of the lung in patients suffering from complications revealed that destruction of the collateral vessels characterized by wide lumen and weak walls is responsible for the postoperative bleeding. Such complications can be prevented by using the TA stapler which cuts off the lung tissue with little or no damage to the other lung tissues. PMID- 2308244 TI - [A case of successful closure of multiple lung fistulae by omental pedicle flap after intrapleural sponge plombage 34 years before]. AB - A case of successful closure of pulmonary fistulae by omental pedicle flap is reported. A 58-year-old female with chronic empyema as a sequela of pulmonary tuberculosis was referred with complaints of fever and purulent sputa. After extirpation of spongy "Plombs" (Vinylsponge) which had filled pleural space in previous operation done 34 years before, omental pedicle flap was fixed by sutures to multiple lung fistulae. Omental pedicle was not filled up all the empyema cavity. We anticipate that an omental pedicle flap covering the lung fistulae will be a simpler but promising method of closing lung fistulae, while simultaneously preventive of infection of residual cavity. PMID- 2308245 TI - [Valve thrombosis of St. Jude Medical prosthesis; report of three cases]. AB - Three cases with valve thrombosis of St. Jude Medical prosthesis (SJM valve) are reported. Incidence of valve thrombosis of SJM valve was 0.15%/patient-year. Cineradiography was useful to make the diagnosis. SJM valves were implanted with the hinges anatomically oriented in mitral position, and in both aortic and tricuspid positions with the leaflet opening parallel to the ventricular septum. Therefore, we recommend that SJM valve should be placed with the hinge antianatomically oriented in mitral position, and in both aortic and tricuspid positions with the leaflet opening to be perpendicular to the interventricular septum, respectively. PMID- 2308246 TI - [A case of ruptured pseudoaneurysm of the aortic arch associated with hemoptysis and hoarseness]. AB - We experienced a case of the ruptured pseudoaneurysm of the aortic arch. Patient complained left anterior chest pain, back pain and hoarseness. Considering the past history of pulmonary tuberculosis, emergency operation was performed median sternotomy approach and using aortic occlusion balloon catheter method and selective cerebral perfusion. Woven dacron graft was anastomosis intraluminal aneurysm. Postoperative course was good. Median sternotomy approach and AOBC method were better than intercostal approach method, because of a little bleeding, short operative time and method. PMID- 2308247 TI - [A case of aorto-coronary bypass surgery in a hypophysectomized male patient]. AB - A 53-year-old hypophysectomized male patient who had been on adjuvant therapy with cortizol and thyroxin, underwent aorto-coronary bypass surgery for angina pectoris with 3 vessel obstruction. Following revascularization surgery, he had an uneventful course until 8th post-operative day, when he experienced about of unconsciousness which was relieved by intravenous hydrocortizon supplement. Simultaneously complicated bradycardia and peripheral coldness were considered to be due to lowered serum T3 and T4 values. By the time the thyroid function stabilized, three times as much as preoperative dosage of thyroxin had to be administered for 34 days. The control of the hypothyroidism plays an important role in the postoperative management of the patient with panhypopituitarism after the cardiac surgery. PMID- 2308248 TI - [A case of modified Fontan operation for complete atrioventricular canal of right dominance with double-outlet right ventricle, common atrioventricular valve regurgitation]. AB - A 6-year-old boy was diagnosed to have complete atrioventricular canal (CAVC) with double-outlet right ventricle (DORV), common atrium and common atrioventricular valve regurgitation. The atrioventricular junction predominantly connected to the right ventricle (right dominance) and the left ventricle was hypoplastic (LVEDV = 64% of normal). The combination of DORV with right dominant CAVC makes more difficult to make intra-ventricular rerouting. A modified Fontan procedure, atrial partition and DeVega's annuloplasty were successfully performed. It is concluded that Fontan procedure might be preferable rather than intra-ventricular rerouting in this case. PMID- 2308249 TI - [A case of primary mediastinal liposarcoma which presents a singular appearance]. AB - An operated case of primary mediastinal liposarcoma is reported. A 71-year-old male who was asymptomatic was unexpectedly pointed out a huge abnormal mass shadow in the mediastinum on the chest roentgenogram, when he caught a common cold. The CT scan showed the singular horseshoe-shaped tumor in the posterior mediastinum which was adjacent to the antero-lateral phase of the vertebrae. MRI was useful to our recognition of its whole shape and localization. Extirpation of the tumor via right postero-lateral thoracotomy was performed successfully. The pathological diagnosis was liposarcoma; well differentiated, lipoma-like type. Primary mediastinal liposarcoma is a very rare mediastinal tumor (0.2%). Thirty six cases of primary mediastinal liposarcoma including our case have been reported at present in Japan, so far as we surveyed. It is generally known that liposarcoma has the low sensitivity to the radiotherapy and chemotherapy and has high incidence of recurrence. We think that this case needs the strict postoperative follow-up. PMID- 2308250 TI - [A case of Marfan syndrome with recurrent bilateral pneumothorax and anuloaortic ectasia]. AB - A 17-year-old male patient with Marfan syndrome was admitted due to recurrent bilateral pneumothorax which had recurred totally 11 times during the past 3 years. For the treatment of obstinately continuing right pneumothorax resection of bullae in combination with pleuropexy using OK 432 was effective. Two months thereafter Bentall operation with a composite graft consisting of a woven Dacron tube and a Bjork-Shiley 27 mm aortic valve prosthesis was performed for his anuloartic ectasia. Left pneumothorax recurred 2 weeks after Bentall operation. But it was treated successfully with OK 432 injection into the left pleural cavity. Now, he is doing well as a student. PMID- 2308251 TI - [A case of mitral stenosis with free floating ball thrombus]. AB - A free floating thrombus in the left atrium is a rare complication of the mitral valvular disease. A 56-year-old woman with mitral stenosis was admitted for cerebral infarction and abdominal pain. A free floating ball thrombus was detected in the left atrium by echocardiography. We performed the emergent open heart surgery for removal of ball thrombus and mitral commissurotomy successfully. The size of thrombus was 4 x 3 x 2 cm. Postoperative course was uneventful. PMID- 2308252 TI - [A case of traumatic hernia of right diaphragma]. AB - A patient with traumatic diaphragmatic hernia at right side was treated surgically. He was 63-year-old male. His illness was caused by a traffic accident one year ago. The major symptoms due to the injury were short breathness and pain at right lateral chest wall. One year later he complained of the nausea and abdominal discomfort. At the right thoracotomy, the herniation of liver and colon through the ruptured diaphragma was found. After the return of herniated organ into the abdominal space, ruptured diaphragma was closed directly. PMID- 2308253 TI - [Technical considerations for the epicardial approach in Wolff-Parkinson-White syndrome]. AB - Epicardial approach consists of meticulous dissection of the annular fat pad of the Kent bundle site and subsequent cryocoagulation from the epicardial side. This technique obviates the need of atriotomy and makes ablation without cardiopulmonary bypass possible. In performing this approach for patients with the left parietal or posteroseptal pathway through median sternotomy, special technical strategies are necessary to keep hemodynamic status stable during dissection and cryoablation procedures, because in these cases apex of the heart has to be retracted upward to approach the Kent bundle site. For this purpose, the use of an ultrasonic surgical aspirator for dissection of the annular fat pad is required. With this instrument fat tissue is emulsified and aspirated by stroking the fat pad gently, easy dissection is possible without injury to major coronary vessels, even through a narrow operative field. Another point is to dissect the annulus fat below the coronary sinus (i.e., at the space between the coronary sinus and circumflex coronary artery), not above it. By doing this extensive retraction of the apex is no longer necessary. In performing cryocoagulation care has to be taken not to involve the coronary artery into the lesion. However, too tight retraction of the coronary artery may cause another risk of thrombosis. Sometimes moderate systemic heparinization should be performed during coronary retraction and cryocoagulation procedure. PMID- 2308254 TI - [A successful repair of post-infarction left ventricular free wall rupture]. AB - Left ventricular free wall rupture secondary to acute myocardial infarction is almost invariably fatal. This report is the case presentation of a successful repair of left ventricular free wall rupture. A 55-year-old man, with a diagnosis of acute infero-lateral myocardial infarction, was transferred from another hospital to our CCU having recurrent chest pain on the fourth day after infarction. Shortly after admission, he lost his consciousness and fell into cardiogenic shock. Echocardiography showed a large pericardial fluid. He was immediately transferred to the operating room with the diagnosis of the heart rupture. After opening the pericardium containing 200 cc of blood, cardiac tamponade was relieved. The posterolateral portion of the left ventricle was found to be bluishly discolored, with a 8 mm-long tear of epicardium. Using cardiopulmonary bypass, the tear was closed with Teflon-reinforced sutures. The post-operative course was uneventful. PMID- 2308255 TI - A method for removing the acrochordon (skin tag). PMID- 2308256 TI - An unusual case of pelvic pain. PMID- 2308257 TI - Aluminum inhibits hemoglobin synthesis but enhances iron uptake in Friend erythroleukemia cells. AB - Aluminum (Al) overload in dialysis patients and experimental animals is associated with the development of anemia. However, the precise mechanisms of erythrocyte Al uptake and toxicity are poorly understood. Al accumulation, hemoglobin (Hb) synthesis and cell growth were evaluated in dimethylsulfoxide (DMSO)-induced Friend erythroleukemia cells (FEC), a model system for erythroid differentiation. FEC were grown in media containing either Al citrate, transferrin-aluminum (Tf-Al), Tf or no additions. Al accumulation occurring only in cells grown in Tf-Al containing media was detected at 24 hours and increased linearly up to 96 hours after induction. By 96 hours, 200 +/- 36 micrograms Al/liter lysed cells were detected in Tf-Al grown cells versus 5 +/- 1 micrograms Al/liter lysed cells in cells grown in Al citrate (P less than 0.001). Tf-Al inhibited Hb synthesis at 72 hours after induction. At 96 hours 50 +/- 15% cells were benzidine positive when grown in Tf-Al compared to 76 +/- 15% in Al citrate (P less than 0.001). FEC grown in increasing concentrations of Tf-Al (100 to 500 micrograms/ml) showed inhibition of Hb synthesis at lower concentrations of Tf-Al at 100 micrograms/ml than for cell growth at 300 micrograms/ml. Higher concentrations of Tf-Al (greater than 300 micrograms/ml) did not further inhibit Hb synthesis or cell growth. Iron (Fe) and Tf uptake were increased in Al loaded FEC compared to control cells. The increased Tf uptake was probably the result of increased Tf receptor expression on FES since Tf cell cycling time was unchanged. These data indicate that Al utilizes the Tf uptake pathway for entry into erythrocyte precursors. Al is toxic at sites distal to Fe uptake, possibly at the heme and/or globin synthetic pathways, resulting in decreased Hb synthesis and cell growth. PMID- 2308258 TI - Protein kinase C in mouse kidney: effect of the Hyp mutation and phosphate deprivation. AB - To test whether protein kinase C plays a role in the regulation of renal brush border membrane phosphate transport and mitochondrial vitamin D metabolism, we examined the activity, distribution and endogenous substrates of protein kinase C in renal subcellular fractions derived from two mouse models exhibiting perturbations in both renal functions. The X-linked Hyp mouse is characterized by reduced phosphate transport and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis relative to normal, whereas the phosphate-deprived mouse exhibits elevated phosphate transport and vitamin D hormone synthesis. Protein kinase C activity was higher in renal cytosol of Hyp mice, when compared to normal littermates (358 +/- 11 vs. 244 +/- 31 pmol 32P/mg prot/min, P less than 0.02), whereas genotype differences in brush border membrane and mitochondrial kinase were not apparent. Phosphate deprivation of normal mice elicited a 50% reduction in brush border membrane protein kinase C (from 819 +/- 56 to 460 +/- 48 pmol 32P/mg prot/min, P less than 0.03), an increase in mitochondrial kinase (from 57 +/- 7 to 87 +/- 10 pmol 32P/mg prot/min, P less than 0.03), and no change in cytosolic kinase activity. Phosphate deprivation of Hyp mice led to an increase in mitochondrial protein kinase C (from 72 +/- 7 to 98 +/- 9 pmol 32P/mg prot/min, P less than 0.03) and no change in either brush border membrane or cytosolic kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308259 TI - Activation of the inflammatory response of neutrophils by Tamm-Horsfall glycoprotein. AB - The activation of human polymorphonuclear leukocytes (PMN) by particulate Tamm Horsfall glycoprotein (THG) represents an interaction hitherto unrecognized. The potential pathophysiological effect of this phenomenon within the interstitium of the kidney is highlighted by the activation of the respiratory burst, as well as by comprehensive PMN degranulation. Products of the interaction are expressed in terms of phagocytosis, luminol-dependent chemiluminescence, granule marker enzyme release and arachidonic acid metabolism. Significant quantities of the primary, secondary and tertiary granule markers, myeloperoxidase, vitamin B12 binding protein and N-acetyl-beta-D-glucosaminidase, respectively, were secreted in a dose and time-dependent manner. Phagocytosis of the glycoprotein was accompanied by the generation of significant quantities of leukotriene B4. Furthermore, the ability of such a particulate ligand to activate the alternative pathway of complement clearly represents a capacity to augment the inflammatory response. Should the interaction of THG with PMN take place within the interstitium of the kidney, augmented by the deposition of complement proteins on the surface of insoluble aggregates, the resulting inflammatory response may lead to marked tissue damage and eventually result in interstitial fibrosis. PMID- 2308260 TI - Glomerular platelet-activating factor levels and origin in experimental glomerulonephritis. AB - The content of platelet activating factor (PAF) in glomeruli isolated from rats with nephrotoxic serum glomerulonephritis (NSGN) was quantified at various stages of the disease and the role of complement, platelets and neutrophils in mediating changes in glomerular PAF levels was evaluated. PAF content was assessed following extraction, isolation and quantification of this alkyl ether lipid using a bioassay based on [3H]-serotonin release from labelled rabbit platelets. Following induction of NSGN using proteinuric doses of rabbit immune serum raised against rat glomerular basement membrane, enhanced glomerular PAF levels were observed at 3 hours, 24 hours and on day 15 following induction of the disease. In complement depleted rats and at three hours following induction of NSGN, glomerular PAF levels were significantly lower than in complement replete controls studied in parallel. At the same time point of the disease, platelet depleted rats with NSGN demonstrated significantly lower glomerular PAF levels than parallel controls, whereas in neutrophil depleted rats glomerular PAF levels were no different than controls. These observations indicate that in infiltrative and complement dependent forms of glomerular immune injury, glomerular PAF levels are increased via a complement mediated mechanism. Infiltrating platelets, but not neutrophils, partially account for the enhanced glomerular PAF levels. The observations are of potential importance in the pathophysiology of glomerulonephritis. PMID- 2308261 TI - Relationship of glomerular hypertrophy and sclerosis: studies in SV40 transgenic mice. AB - We previously described the development of glomerulosclerosis in mice transgenic for large T-antigen, a gene whose in vitro expression markedly increases proliferation of cultured cells. In the current study we sought to determine the effect of unilateral nephrectomy on these sclerosis-prone animals which have a genetically defined potential for increased renal growth. In comparison with sham nephrectomy animals, nephrectomized transgenic female mice had significantly larger kidneys, larger glomeruli (5886 mu2 npx vs. 3796 mu2 sham), more cells per glomerulus and more severe glomerulosclerosis. Nephrectomized transgenic male animals had variable increases in kidney size, no significant increase in glomerular size (4750 mu2 npx vs. 4502 mu2 sham) or cellularity, and no worsening of glomerulosclerosis. In non-transgenic female animals nephrectomy induced an increase in kidney size but not in glomerular size (2640 mu2 npx vs. 2625 mu2 sham) and failed to induce glomerular lesions. A close correlation (r = 0.91) was found between glomerular size and severity of glomerulosclerosis in these animals. This finding supports the hypothesis that a pathophysiologic link exists between glomerular enlargement and glomerulosclerosis. We also found that increases in total kidney size and glomerular size did not consistently parallel each other, that is, renal hypertrophy may occur without an increase in glomerular size. This finding suggests that total kidney growth and glomerular growth may be independently regulated or may have different thresholds for activation following unilateral nephrectomy. PMID- 2308262 TI - Hyperplasia precedes increased glomerular filtration rate in rat remnant kidney. AB - Using 3H-thymidine (3H-T), we examined DNA synthesis in rats subjected to either uninephrectomy (UNI), five-sixths nephrectomy (R) or sham (S) surgery. Twenty four, 48, or 72 hours later, animals were infused with 14C-inulin, PAH and 3H-T and clearances obtained. Prior to sacrifice, India ink was injected for glomerular counting. By 24 hours, glomerular filtration rate per nephron was significantly increased in UNI. However, in R, glomerular filtration rate per nephron was significantly lower than S until 72 hours. Total micrograms DNA per nephron was unchanged in UNI but significantly increased in R compared to S at all times. 3H-T incorporation into DNA was twice as great in UNI as in S was over five-fold greater at 24 hours in R than in S; this marked increase persisted in R at 48 and 72 hours. Autoradiographs confirmed that DNA was synthesized predominantly by renal tubular cells and not infiltrating cells. These results indicate that hyperplasia in compensatory renal growth is related to the quantity of tissue removed and that, in the remnant kidney, DNA synthesis precedes the compensatory increase in glomerular filtration rate per nephron. PMID- 2308263 TI - Adrenergic modulation of potassium metabolism in uremia. AB - The effect of chronic beta adrenergic blockade on potassium homeostasis during moderate intensity exercise (40% of VO2 max) was examined in seven end-stage renal patients who were being maintained on chronic dialysis treatment. Subjects participated in three study protocols: 1) exercise alone, 2) exercise plus propranolol (a nonselective beta-1, beta-2 antagonist), and 3) exercise plus metoprolol (a specific beta-1 antagonist). The basal potassium concentration was similar in all three studies and averaged 4.95 +/- 0.12 mEq/liter. During Study 1 (exercise alone), plasma potassium rose by 0.26 +/- 0.09 mEq/liter. During exercise with propranolol, plasma K concentration rose significantly higher (delta plasma K = 0.44 +/- 0.26 mEq/liter; P less than 0.05 vs. exercise alone). In contrast, the rise in plasma K during exercise with metoprolol (delta plasma K = 0.20 +/- 0.08 mEq/liter) was similar to that observed with exercise alone. Differences in potassium homeostasis between metoprolol and propranolol could not be explained by differences in hemodynamic parameters, levels of potassium regulatory hormones, or acid base status. Thus, the higher rise in potassium concentration during exercise with propranolol could only be explained by adrenergic blockade at the beta-2 receptor site. These results support the concept that adrenergic control of extrarenal potassium homeostasis in dialysis patients is mediated at the beta-2 receptor. Since a deterioration in potassium homeostasis during exercise is observed with beta-2, but not beta-1 blockade, selective beta-1 adrenergic blocking agents may be safer in dialysis patients. PMID- 2308265 TI - Analysis of magnesium in tubular fluid using flameless atomic absorption spectrophotometry. PMID- 2308264 TI - Use of modified fine needle aspiration for study of glomerular pathology in human kidneys. AB - In routine fine needle aspiration (FNA) of the kidney, the glomeruli are seldom visualized. They appear as multi-layered, cellular conglomerates and, therefore, are unsuitable for morphological analysis. A novel plasma-clot technique for collection of glomeruli from FNA samples was used in a study of 6 native and 24 transplanted human kidneys with suspected glomerular lesions. This technique produced a satisfactory yield of well preserved glomeruli and enabled the identification of glomerular pathology with the accuracy comparable to that of renal core biopsy. The FNA plasma clot method may prove useful in the study of glomerular pathology under conditions where the use of percutaneous biopsy is conventionally limited or avoided. PMID- 2308266 TI - Class differentiation of immunoglobulin-containing cerebrospinal fluid cells in inflammatory diseases of the central nervous system. AB - An immunocytochemical technique allowing repeated use of antisera is applied to identify immunoglobulin-containing cells (ICC) of the IgG, IgA, and IgM class in the cerebrospinal fluid (CSF) of 298 patients with various neurological disorders. The demonstration of ICC in the CSF is highly indicative of an inflammatory disease (p less than 0.0001; Chi-square test). In the group of noninflammatory disorders ICC are only found in three cases of lymphomas, two dysgerminomas, and one glioblastoma. ICC of all classes are seen in acute viral and bacterial infections of the CNS including tick-borne meningopolyneuritis Bannwarth. IgG-positive ICC predominate in chronic inflammatory disorders like multiple sclerosis and HIV encephalitis. In HIV-positive patients IgA- or IgM positive cells are strongly indicative of an opportunistic infection of the brain. Persistent high levels of ICC in three patients with bacterial meningitis are associated with a fatal outcome. PMID- 2308267 TI - Treatment of polycythemia vera by isovolemic large-volume erythrocytapheresis. AB - Excess red blood cells (RBC) in patients with polycythemia vera (PV) are usually removed by repeated phlebotomy. In order to improve the efficacy of this treatment, we used isovolemic large-volume erythrocytapheresis (EA) by a cell separator. A retrospective analysis of our experience with 69 PV patients (206 EA procedures) is reported. EA induced a rapid, well-tolerated, and long-lasting reduction of Hct, Hb, and RBC counts, as well as an immediate disappearance or reduction of clinical symptoms of PV, while tissue oxygen tension - as measured in 8 patients - increased. Hct was reduced by EA from 56.8% +/- 5.6% to 41.9% +/- 6.6%, Hb from 17.5 +/- 2.3 to 12.7 +/- 2.4 g%, RBC counts from 7.4 +/- 0.9 to 5.4 +/- 0.9 x 10(6)/mm3. The mean volume of the apherisate was 1410 +/- 418 ml, (mean Hct 79.7% +/- 9.3%), and the actual RBC volume removed 1113 +/- 367 ml. The isovolemic procedure was well tolerated and the acceptance by patients seemed to be better than with repeated phlebotomy. In 21 patients whose Hct values (Hct before and after EA 58% +/- 5.7% and 41.5% +/- 4.9%) were regularly followed after EA the mean period with Hct less than 50% after a single EA procedure was 6.1 +/- 4.1 months (median, 6); in 14 out of these 21 patients a Hct of less than 43% after EA was reached and their mean period with Hct less than 50% after EA was 7.6 +/- 4.0 months (median, 7.5). For three patients this period was 11, 13, and 15 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308268 TI - Plasma plasmalogens of the phosphoethanolamine type and angiopathy in diabetic patients. PMID- 2308270 TI - A second chance. PMID- 2308269 TI - Gastrointestinal type 1 hypersensitivity to azathioprine. AB - We report the case of a 49-year-old patient with progressive sensomotor polyneuropathy who developed nausea, vomiting, and diarrhea after 2 1/2 months of azathioprine therapy. Administration of the drug was interrupted. These symptoms recurred immediately after rechallenge with azathioprine. A duodenal biopsy demonstrated a massive local eosinophilia without peripheral blood eosinophilia. Cutane testing with azathioprine showed a positive type 1 reaction. We diagnosed a hypersensitive reaction type 1 in the duodenal mucosa on the basis of the histological features, the history, and the cutane reaction. PMID- 2308271 TI - Screening tests identify the prevalence of alcohol use among freshman medical students and among students' family of origin. PMID- 2308272 TI - PWI: practicing while intoxicated addictions and the State Board of Medical Examiners. PMID- 2308273 TI - Bright lights in dark places: physician recognition of alcoholism. PMID- 2308274 TI - Intervention: raising the bottom. PMID- 2308275 TI - Two ships in the night. Physician usage of community drug and alcohol treatment centers. PMID- 2308276 TI - Observations on the management of alcohol withdrawal syndrome. PMID- 2308277 TI - Never try to carry a drunk by yourself. Effective use of self-help groups. PMID- 2308278 TI - Baby bottles and family rattles. Children and substance abuse. AB - Research shows that problem behaviors manifested early tend to persist into later life. Problem drinking does not necessarily commit the young adolescent to a life course of this behavior, but it does alter the probabilities. Conversely, early abstinence is a strong predictor of later healthful behavior. An important observation is that alcohol and other drug use tends to decrease along with smoking decreases. Young adolescents tend to believe that most of their peers engage in a particular type of behavior whether that is the actual case or not. There is a tendency across populations of adolescents to overestimate such behaviors by a factor of six or eight. In one study, school children estimated that about two-thirds of their peers smoked while the actual figure was about one tenth. Adolescents tend to have weak orientation to the future, especially in regard to consequences of risk-taking behavior. College-bound adolescents tend to have a longer view of the future than those who do not pursue college, but in general adolescents think, "It can't happen to me," or, "It's so far off that I just can't think about it." They are focused on the here and now. Many youngsters when they think about it have a dismal view of the future. They are doubtful about their own ability to influence events in ways that build toward a rewarding life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308279 TI - One big happy family and other myths. PMID- 2308280 TI - Staying off the merry go round: prescribing habits for recovering patients. PMID- 2308281 TI - Was superman a junky? The fallacy of anabolic steroids. PMID- 2308282 TI - What'd he say? Street drug terminology. PMID- 2308283 TI - Alcoholism and other drug abuse. The South Carolina Story. Introduction. PMID- 2308284 TI - Educational factors in substance abuse for physicians. PMID- 2308285 TI - Why bother? Reasons for action. PMID- 2308286 TI - I am a chemical. PMID- 2308287 TI - Who heals the healer? The history and purpose of the Physicians Assistance and Advocacy Committee. PMID- 2308288 TI - The fate of the foreskin. PMID- 2308290 TI - High tech, high touch. PMID- 2308289 TI - Fast medicine and high-tech healing. PMID- 2308291 TI - Collagenous colitis. PMID- 2308292 TI - How good is the Pap smear? PMID- 2308293 TI - Testing for inhalant allergies. PMID- 2308294 TI - Mechanical ventilation: weaning problems and techniques. PMID- 2308295 TI - Gonococcal endocarditis: report of a case and review of the literature. AB - Gonococcal endocarditis may appear in the extremes of cardiogenic and septic shock. These patients must be quickly stabilized and evaluated by echocardiography and cardiac catheterization where possible. Urgent surgical intervention for valve replacement may be necessary before complete stabilization of the patient's cardiac hemodynamics status is accomplished. Although the aortic valve is most commonly involved with gonococcal endocarditis, the mitral valve is involved as well and may present as a true emergency situation. Right-sided valve infections may be treated by a more conservative medical means if the patient does not deteriorate into a hemodynamic instability. Deterioration of the patient requires immediate intervention with catheterization and surgery in the absence of positive blood cultures to confirm the diagnosis of gonococcal endocarditis. Once the need for emergency surgical valve replacement has been determined the rules of complete debridement of all infected tissues, insertion of sutures into healthy annular tissue, and selection of an appropriate mechanical valve apply. Long-term antibiotic therapy is included in post-operative management. PMID- 2308296 TI - Identification of a frequency response model of joint rotation. AB - A second order, linear oscillator transfer function model is fit to the measured transfer function relating the abduction-adduction rotation of the first finger to the applied moment. Nearly constant isometric contractions of the first palmar and dorsal interossei are maintained by the subjects during the measurements. The stiffness and damping components of the identified models increase significantly with increasing isometric contraction when compared to those recorded under relaxed contraction. Muscle fatigue causes the natural frequency, damping ratio and stiffness of the joint rotation to decrease under full isometric contraction, and it causes the natural frequency and stiffness to increase when the muscles are relaxed. PMID- 2308297 TI - Numerical study on the unsteady flow of non-Newtonian fluid. PMID- 2308298 TI - A robust, accurate load cell for use in training above-knee amputees. PMID- 2308299 TI - Stiffness characteristics of the circular Ilizarov device as opposed to conventional external fixators. AB - Ilizarov proposes the use of a special circular fixation device for treatment of bone defects and nonunions or for limb lengthening. Supposition was that the success of this method has to do with the specific mechanical behavior of the device. This behavior is a result of the configuration of the fixation elements. Therefore, a mechanical study of the sensitivity of the circular compression and distraction device (CDD) to configuration parameters was performed. The CDD was found to exhibit a nonlinear stiffness behavior, in particular under axial load. This may be favorable for the induction and tolerance of bone formation. Among the different parameters tested the ring radius was the most important with respect to stiffness. In general, the stiffness of the CDD allows adjustment during postoperative management. In magnitude, it is equal or lower when compared to other fixator types. PMID- 2308300 TI - Cracks emanating from circular voids or elastic inclusions in PMMA near a bone implant interface. AB - Mechanical fracture is believed to be a primary reason for loss of fixation at the bone-cement-implant interface. In addition to the expected cracks at the bone cement interface, cracks are also observed to be formed at voids and inclusions within the cement. An analytical solution is presented for cracks emanating from circular voids or elastic inclusions under uniaxial tension using the solution for a single dislocation as a Green's function. Stress intensity factors are calculated for arbitrary orientations of the cracks, and for varying relative stiffnesses of the inclusion and the matrix, to determine the most favorable combination of parameters for crack growth. PMID- 2308301 TI - Large deformation analysis of orthodontic appliances. AB - The deformations of orthodontic appliances used for space closure are large so that any mathematical analysis will require a nonlinear approach. Existing incremental finite element and finite difference numerical methods suffer from excessive computational effort when analyzing these problems. An accurate segmental technique is proposed to handle these difficulties in an extremely efficient fashion. The segmental technique starts by assuming that an orthodontic appliance is composed of a number of smaller segments, the ends of which undergo small relative rotation. With an appropriate choice of local coordinate system the equilibrium equations for each segment are linearized and solved in a straightforward manner. The segments are then assembled using geometric and force compatibility relations similar to the transfer matrix method. Consequently, the original nonlinear boundary value problem is solved as a sequence of linear initial value problems which converge to the required boundary conditions. As only one segment need be considered at a time, the computations can be performed accurately and efficiently on a PC type computer. Although an iterative solution is used to match the boundary conditions, the time required to solve a given problem ranges from a few seconds to a couple of minutes depending on the initial geometric complexity. The accuracy of the segmental technique is verified by comparison with an exact solution for an initially curved cantilever beam with an end load. In addition, comparisons are made with existing experimental and numerical results as well as with a new set of experimental data. In all cases the segmental technique is in excellent agreement with the results of these other studies. PMID- 2308302 TI - Surface strain variation in human patellar tendon and knee cruciate ligaments. AB - Local surface strains in bone-fascicle-bone subunits from human patellar tendon and anterior and posterior cruciate ligaments were measured between markers using low-speed photography during low rate subfailure testing. A simple stress-strain relationship of the power form was found to describe the bone-to-bone responses up to four percent strain for all three tissue types examined. The regional material behavior were best fit using an inverted strain-stress relationship, however. The power model, fitted to the experimental data, conformed to the expected stress-strain relationship better than either the quadratic or cubic models. With few exceptions, for a given stress, the strains near the proximal and distal bone ends were not significantly different from each other, but were significantly higher than the strains in the tissue midregions. Local strain patterns generally varied among subunits from the same tissue. PMID- 2308303 TI - Measurement of changes in ligament tension with knee motion and skeletal maturation. AB - This study was designed to determine the in situ strains, stresses, and loads in the medial collateral ligament (MCL) of skeletally immature and mature rabbits. Using a noncontact method, the magnitudes of the in situ strains were first determined as a function of knee flexion angle. The MCL was divided into three anatomical regions (anterior, middle, and posterior) across its width. For strain measurements, the variation of a gauge length in these regions was obtained in the intact knee at 60, 90, and 120 deg of flexion. Subsequently, all soft tissues around the knee were dissected away, leaving the femur-MCL-tibia (FMT) complex. The MCL was allowed to retract freely and the new length, called the zero length, was measured. From this, the in situ strains were determined. To obtain the stress-strain relationship of the FMT complex, the specimens were subjected to tensile testing. Knowing the in situ strains and the stress-strain relationship, the in situ stresses in the three anatomical regions of the MCL were determined as a function of knee flexion angle. Multiplying these stresses by 1/3 of the cross-sectional area and summing the loads thus calculated, the in situ loads of the MCL were obtained. Our data suggest that the in situ load in the MCL is not large within the range of knee flexion angles studied, i.e., 1.4 to 2.7 N for the skeletally immature animals and 3.0 to 5.8 N for the skeletally mature animals. An increase in the in situ load with skeletal maturation was demonstrated. PMID- 2308304 TI - Muscle activation and contraction: constitutive relations based directly on cross bridge kinetics. AB - This paper reviews recent work aimed at deriving tractable constitutive relations for skeletal muscle from biophysical cross-bridge theories. Discussion is focused on a model proposed previously by the first author (the Distribution-Moment Model), which emphasizes the important role of the moments of the actin-myosin bond-distribution function. The theory leads to a relatively simple third order state variable model for contraction dynamics in which the state variables are the three lowest order moments of the bond-distribution function; further, these three moments have simple macroscopic interpretations as muscle stiffness, force, and elastic energy. New results are presented on the formulation of a compatible model for excitation-contraction coupling, and this model requires the introduction of only one more state variable--the free calcium concentration. PMID- 2308305 TI - In-vivo indentation of human skin. AB - Indentation tests were carried out on the forehead skin of volunteers under loading pressures of 0-5 KPa. The indentation was found to increase asymptomatically with loading pressure. In an attempt to develop a quantitative index for aging of the skin, its response to indentation loading was analyzed in reference to its glycosaminoglycan (GAG) containing ground substance and fibers' network microstructure. An analytic model that considers the skin as an incompressible solid-fluid mixture was developed and utilized to simulate the skin's indentation response. Following parameter fitting, the predicted results are in close agreement with the data. The model can thus serve as a tool for evaluating the effect of changes in the dermis components which accompany aging. PMID- 2308306 TI - Effect of hypertension on elasticity and geometry of aortic tissue from dogs. AB - Inflation-extension experiments were carried out on segments of the descending thoracic aortas from 4 normotensive and 4 hypertensive dogs rendered hypertensive using either unilateral or bilateral renal artery constriction. Intravascular pressures up to 200 mm Hg and axial forces up to 200 g were used. The external diameter of the segment and the distance between two longitudinally spaced gage marks were recorded photographically at each pressure-force level combination. Dimensions in the underformed configuration were measured at the end of the inflation-extension experiment. Data were analyzed for changes in geometry and force-deformation response. Results indicate that: 1. Under sustained hypertension the wall thickness in the underformed configuration increases with a concurrent reduction in the in-situ longitudinal extension ratio. 2. This dual tissue response accomplishes substantial reductions in the circumferential and longitudinal stresses from the levels that would be reached at equivalent pressures in the absence of these geometric changes. 3. At comparable intravascular pressures the extensibility in the circumferential direction is slightly greater for the hypertensive aortas as compared to normals. However, the stress-extension ratio relationship in the circumferential direction is similar in the two groups. 4. The stress-extension ratio relationship in the longitudinal direction indicates that the hypertensive aorta is stiffer than its normotensive counterpart. PMID- 2308307 TI - Experimental analysis of pulsatile flow through elastic collapsible tubes: application to cardiac assist device. AB - This study presents a simulated analysis of Phased Compression Cardiac Assist Device (PCCAD) and evaluation of its applicability as a non-invasive temporary assist for a failing heart. The new technique is based on the chest pump mechanism for blood flow augmentation during external massage by phased compression of the abdominal and thoracic cavities. A semi-closed hydraulic system to simulate the systemic circulation was constructed; the system includes a left ventricle which functions according to the Starling principle and a pneumatic system which controls the pressures applied to the thoracic and abdominal cavities, in complete synchronization with the beating normal or failing heart. The possibility of manipulating the three pumps in series (venous, heart, and arterial) has been checked, and the principal parameters which effect the efficiency of the PCCAD were evaluated. This in vitro analysis shows the high potential of a non-invasive temporary cardiac assist device. It points to the necessary measures one has to take in order to achieve good synchronization and to interfere externally with the augmentation of cardiac output or with the augmentation of root aortic pressure. PMID- 2308308 TI - An evaluation of the Weinbaum-Jiji bioheat equation for normal and hyperthermic conditions. AB - The predictions of the simplified Weinbaum-Jiji (WJ) bioheat transfer equation in one dimension are compared to those of the complete one-dimensional three equation model that represented the starting point for the derivation of the WJ equation, as well as results obtained using the traditional bioheat transfer equation of Pennes [6]. The WJ equation provides very good agreement with the three-equation model for vascular generations 2 to 9, which are located in the outer half of the muscle layer, where the paired vessel diameters are less than 500 microns, under basal blood flow conditions. At the same time, the Pennes equation yields a better description of heat transfer in the first generation, where the vessels' diameters are greater than 500 microns and epsilon, the vessels' normalized thermal equilibration length, is greater than 0.3. These results were obtained under both normothermic and hyperthermic conditions. A new conceptual view of the blood source term in the Pennes equation has emerged from these results. This source term, which was originally intended to represent an isotropic heat source in the capillaries, is shown to describe instead the heat transfer from the largest countercurrent microvessels to the tissue due to small vessel bleed-off. The WJ equation includes this effect, but significantly overestimates the second type of tissue heat transfer, countercurrent convective heat transfer, when epsilon greater than 0.3. Indications are that a "hybrid" model that applies the Pennes equation in the first generation (normothermic) and first two to three generations (after onset of hyperthermia) and the Weinbaum Jiji equation in the subsequent generations would be most appropriate for simulations of bioheat transfer in perfused tissue. PMID- 2308309 TI - Secondary flow velocity patterns in a pulmonary artery model with varying degrees of valvular pulmonic stenosis: pulsatile in vitro studies. AB - The objective of this study was to characterize in detail the secondary flow velocity patterns in an in vitro model of a human (adult) pulmonary artery with varying degrees of valvular pulmonic stenosis. A two-dimensional laser Doppler anemometer (LDA) system was used to map the flow fields in the main (MPA), left (LPA), and right (RPA) branches of the pulmonary artery model. The study was conducted in the Georgia Tech right heart pulse duplicator system. A pair of counter-rotating secondary flows were observed in each daughter branch in which the fluid moved outwardly along the side walls and then circled back inwardly toward the center of the vessel. For the case of the "normal" valve, the two counter-rotating secondary flows were symmetric about the centerline. The strength of secondary flows in the RPA was much stronger than in the LPA. However, as the pulmonic valve became more stenotic, the two counter-rotating secondary flows in both the LPA and RPA were no longer symmetric. In addition, the strength of secondary flows in both daughter branches increased with increasing degree of valvular stenosis. The increment in the LPA was, however, greater than in the RPA. The study demonstrates the importance of analyzing complex biological flows from a three-dimensional viewpoint. PMID- 2308310 TI - The dynamics of the subtalar joint in sudden inversion of the foot. AB - The human subtalar joint was modelled as a quasi-linear second-order underdamped system to simulate sudden inversion motion of the foot relative to the shank. The model was fed with experimental data obtained from six subjects on a specially constructed apparatus. A total of 35 deg inversion was produced on the tested leg rapidly enough (lasting less than 40 ms) in order to ensure that the protective muscles are not activated. The parameters of the joint were evaluated and the following ranges were obtained at 35 deg inversion: elastic stiffness 14-52 Nm rad-1, damping coefficient 1.4-2.9 Nms rad-1, and natural frequency 78-125 Hz. The effects on the test parameters of weight bearing amount, foot dominance, and protective footwear were studied on one subject. PMID- 2308311 TI - The foul-smelling, removable tonsillar concretion: a poorly appreciated manifestation of colonization with Actinomyces. PMID- 2308312 TI - Trauma in pregnancy. PMID- 2308313 TI - CT scan of the abdomen in the evaluation of splenic infarction. PMID- 2308314 TI - A fatal case of hiccups. PMID- 2308315 TI - A case of Goodpasture's disease and interstitial pulmonary infiltrates. PMID- 2308316 TI - Tuberculosis in Tennessee: current trends and program update. PMID- 2308317 TI - Continuing supervision of staff--a necessity. PMID- 2308318 TI - Looking for a silver lining. PMID- 2308319 TI - Solidarity. PMID- 2308320 TI - Effects of fetal alcohol exposure on brain 5 alpha-reductase/aromatase activity. AB - The local formation of the testosterone metabolites 5 alpha-dihydrotestosterone and 17 beta-estradiol within the hypothalamic-preoptic area (HPOA) is essential for the normal sexual differentiation of the male central nervous system (CNS) during a perinatal critical period in the rat. Testosterone, the substrate for these reactions, is derived primarily from synthesis within the fetal testis. Fetal alcohol exposure (FAE) during this critical period profoundly affects fetal testicular steroidogenesis as well as the sexual differentiation of the CNS. The present study was conducted to determine whether FAE directly affects the local metabolism of androgens within the developing CNS or whether reduced androgen substrate, via a testicular lesion, is a more likely explanation for the known effects of FAE on the CNS. The enzymatic activities of 5 alpha-reductase and aromatase were simultaneously quantitated in the newborn rat HPOA following FAE. Neither the enzymatic activity of 5 alpha-reductase, aromatase nor their ratio were significantly influenced (P greater than 0.05) by FAE with respect to controls. FAE apparently does not alter the disposition of the androgens within the newborn rat HPOA. These results support the hypothesis that FAE alters the sexual differentiation of the CNS through inhibition of androgen biosynthesis at the level of the perinatal rat testis. PMID- 2308321 TI - Inhibition of microbial cholesterol oxidases by dimethylmorpholines. AB - Cholesterol oxidase is a potentially important enzyme in steroid transformations, catalysing the conversion of 3-hydroxy-5-ene steroids to 3-keto-4-ene derivatives via a 3-keto-5-ene intermediate. Morpholine derivatives, especially fenpropimorph and tridemorph, were found to block selectively the isomerisation activity of cholesterol oxidases isolated from Nocardia erythropolis, Streptomyces sp., Pseudomonas testosteroni and Schizophyllum commune. These enzymes differ strongly in physical characteristics and catalytic behaviour. The effectiveness of the inhibitors varied with the cholesterol oxidase tested. Fenpropimorph was most effective with each of the 4 enzymes, 50 mg/l inhibiting about 50% of the enzyme activity. Inhibition was instantaneous and followed a reversible competitive mechanism in Streptomyces sp. and a reversible non-competitive mechanism in Nocardia erythropolis and Schizophyllum commune. An irreversible type of inhibition was observed for P. testosteroni cholesterol oxidase. PMID- 2308322 TI - Microbial transformations of steroids--VI. Transformation of testosterone and androstenedione by Botryosphaerica obtusa. AB - The 7 beta progesterone-hydroxylating microorganism Botryosphaerica obtusa was tested for its ability to hydroxylate at this site the C-19 androstene-based compounds, androstenedione (androst-4-ene-3,17-dione) and testosterone (17 beta hydroxyandrost-4-en-3-one). Only very limited 7 beta hydroxylation of both substrates was observed. The products included traces of 7 beta monohydroxytestosterone and 6 beta,7 beta-dihydroxyandrostenedione from testosterone, and of 6 beta,7 beta-dihydroxyandrostenedione from androstenedione. 6 beta,7 beta-Dihydroxyandrostenedione does not appear to have been reported previously as a microbial transformation product. Both substrates were monohydroxylated in significant amounts at the isomeric 7 alpha site and at the 6 beta site. Testosterone was also significantly monohydroxylated at the 15 alpha site and in minor amounts at the 11 alpha and 12 beta sites. Some monohydroxytestosterones had also been oxidised at their 17-OH group, converting them into the corresponding monohydroxy androstenediones. The 7 alpha-hydroxy metabolites and 15 alpha-hydroxytestosterone being chemically demanding to synthesis are valuable microbial transformation products. PMID- 2308323 TI - Concentration decrease of corticosteroid binding globulin (CBG) in plasma of the mare throughout pregnancy. AB - A significant decrease of CBG binding capacity in plasma of the mare throughout pregnancy was demonstrated using equilibrium dialysis and gel equilibration methods. As indicated with immunoelectrophoresis experiments, the pregnancy related fall of CBG binding capacity was linked to an actual decrease in blood CBG concentration. This result contrasts sharply with data on most other mammalian species, with the exception of the gestating rhesus monkey. PMID- 2308324 TI - Aromatase inhibition by 4-thiosubstituted-4-androstene-3,17-dione derivatives. AB - The synthesis and evaluation of 4-thiosubstituted-4-androstenedione analogs as inhibitors of estrogen synthetase (aromatase) is described. All compounds were prepared by the addition of various thiol reagents to 4 beta,5 beta epoxyandrostanedione. Inhibitory activity of synthesized compounds was assessed using a human placental microsomal preparation as the enzyme source and [1 beta 3H]4-androstene-3,17-dione as substrate. Synthesized compounds exhibiting high inhibitory activity were further evaluated under initial velocity conditions to determine apparent Ki values. Several compounds were effective competitive inhibitors, and have apparent Ki values ranging from 34 to 52 nM, with the apparent Km for androstenedione being 54 nM. The results of these studies demonstrate a tightly fitted enzyme pocket that can accommodate bulky substituents at the C-4 position of androstenedione not to exceed 4.3 A in width and 5.5 A in length. PMID- 2308326 TI - A novel chromatographic resolution of 21-hydroxysteroid metabolites of progesterone. AB - 21-Hydroxysteroid metabolites of both progesterone and deoxycorticosterone are excreted in rabbit urine and are eluted from an alumina adsorption column after 21-deoxysteroids. The separation is independent of polarity and dependent on the interaction of the 21-hydroxyl function with the adsorbent. The group separation of these steroids allowed further analysis by high performance liquid chromatography and revealed different proportions of metabolites. This is the first report of the excretion of 21-hydroxysteroid metabolites of progesterone in rabbit urine. PMID- 2308325 TI - Testosterone metabolism in peripheral nerves: presence of the 5 alpha-reductase-3 alpha-hydroxysteroid-dehydrogenase enzymatic system in the sciatic nerve of adult and aged rats. AB - Previous reports from this laboratory indicate that the 5 alpha-reductase, the enzyme which converts testosterone into its "active" metabolite 5 alpha-androstan 17 beta-ol-3-one (dihydrotestosterone, DHT) is highly concentrated in the white matter structures of the CNS, which are mainly composed of myelinated fibers. No studies have been performed up to now, in order to evaluate the possible presence of the 5 alpha-reductase activity in peripheral myelinated nerves. To this purpose the 5 alpha-reductase activity has been evaluated in the sciatic nerve of the rat and compared to that present in the cerebral cortex and in the subcortical white matter, a central structure mainly composed of myelinated fibers. The study has been performed in normal adult male rats (60-90-day-old) and in aged (20-month-old) animals. The data obtained in 60-90-day-old animals indicate the presence of an active metabolism of testosterone at the level of the sciatic nerve. In this structure, testosterone is actively transformed into DHT and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); in the sciatic nerve, the formation of DHT is equal to that found in the subcortical white matter and higher than that found in the cerebral cortex. Moreover, at variance with what happens in CNS structures, where 3 alpha-diol is produced only in small amounts, in the sciatic nerve this metabolite is produced in amounts similar to those of DHT. The study in aged rats has shown that in the sciatic nerve, the formation of DHT and particularly that of 3 alpha-diol are much lower than in younger animals. No age-related variations in the 5 alpha-reductase activity in the cerebral cortex and in the subcortical white matter have been observed. PMID- 2308327 TI - Progesterone side-chain degradation beside hydroxylation with Rhizopus nigricans depends on the presence of nutrients. AB - In the absence of nutrients, Rhizopus nigricans transforms progesterone into a mixture of 11 alpha-hydroxy-4-androstene-3,17-dione and 11 alpha-hydroxy-1,4 adrostadiene-3,17-dione. The same mixture is obtained by the transformation of testosterone and its acetate. PMID- 2308329 TI - The relationship of free fatty acids with the binding of oestradiol to SHBG and to albumin in women. AB - Free fatty acid concentration, sex hormone binding globulin (SHBG) concentration, % free oestradiol and % SHBG-bound oestradiol were measured in fasting and non fasting serum samples from 48 women. Free fatty acids were 128% higher (P less than 0.001) and % SHBG-bound oestradiol was 11% lower (P = 0.001) in fasting than non-fasting samples, but these changes were not significantly correlated (r = 0.16, P = 0.287). Mean SHBG concentration and % free oestradiol did not differ significantly between fasting and non-fasting samples. Between subject correlations were calculated for measurements from 30 premenopausal women: % free oestradiol was inversely correlated with SHBG and free fatty acids and positively correlated with Quetelet's Index; % SHBG-bound oestradiol was positively correlated with SHBG but was not consistently or significantly related to free fatty acids or Quetelet's Index. It was concluded that physiological increases in free fatty acid concentrations do not increase % free oestradiol and that free fatty acids are less important than SHBG concentration and perhaps other variables in determining differences between individuals in oestradiol binding to SHBG. PMID- 2308328 TI - sn-1,2 dioctanoylglycerol mimics the effects of angiotensin II on aldosterone production and potassium permeability in isolated bovine glomerulosa cells. AB - In order to elucidate the possible role in glomerulosa cells of diacylglycerol released by angiotensin II we have studied the action of a synthetic diacylglycerol, sn-1,2-dioctanoylglycerol (DiC8), on aldosterone production and potassium permeability in bovine adrenal cells. DiC8 elicited an increase in 86Rb efflux from cells previously equilibrated with the isotope. The action of DiC8 on the rate coefficient for 86Rb efflux was similar to that previously described for angiotensin II (Am. J. Physiol. 254 (1988) E144-149), i.e. DiC8 induced an immediate increase in 86Rb efflux followed by a sustained decrease in potassium permeability. This DiC8 induced inhibition was observed even in the presence of depolarizing concentrations of potassium. The effect of DiC8 on aldosterone secretion from adrenal glomerulosa cells was measured using a perifusion system. DiC8 (300 microM) caused a significant increase of aldosterone production, comparable to that seen with angiotensin II (100 nM). These results indicate that DiC8 has similar effects to angiotensin II on both potassium permeability and steroidogenesis, which suggests that activation of protein kinase C is involved in the changes of ionic permeability induced by this hormone in bovine adrenal glomerulosa cells. PMID- 2308330 TI - Microsomal dexamethasone binding sites identified by affinity labelling. AB - Binding studies with [3H]dexamethasone identified a class of binding sites on male rat liver microsomes. The binding sites were glucocorticoid-dependent and specific for glucocorticoids and progestins. Scatchard binding parameters, competition studies with triamcinolone acetonide, a synthetic glucocorticoid which competes well for the glucocorticoid receptor, and immunoblotting with an antiglucocorticoid receptor antibody indicated that these sites are distinct from the cytosolic glucocorticoid receptor. Affinity labelling experiments with [3H]dexamethasone 21-mesylate revealed two specifically labelled peptides, one at approx. 66 kDa and a doublet at 45 kDa. The 66 kDa peptide had been previously identified in serum and may be present as a result of serum contamination of the microsomal preparation. The 45 kDa doublet, on the other hand, had been shown to be absent from rat serum. The characteristics of the 45 kDa peptide(s) were identical to those of the dexamethasone binding site identified in the binding studies. [3H]Dexamethasone binding characteristics and affinity labelling of microsomal subfractions, separated by isopycnic centrifugation, showed that the binding sites are located in the endoplasmic reticulum. The identification and role of the 45 kDa peptide doublet remain to be determined. PMID- 2308331 TI - Steroid determinations in human ovarian follicular fluid using capillary gas chromatography. AB - A method is presented based on capillary GLC using both a thermionic and a flame ionization detector to simultaneously analyse all major unconjugated steroids in ovarian follicular fluids (FF). Although specificity can not always be guaranteed for the smaller concentrations of androstenedione and cortisol, accuracy and reproducibility are excellent for the major progestagens and estrogens (progesterone, 17- and 16 alpha-hydroxyprogesterone, pregnenolone, 20 alpha dihydroprogesterone, estradiol and estrone). Above all the analysis is performed with relatively cheap instrumentation and products. Apart from the "profiles" of unconjugated steroids, a semi-quantitative analysis of steroid conjugates is possible if a preliminary group separation with disposable anion exchanger columns is included. PMID- 2308332 TI - Androgen and estrogen dynamics: stability over a two year interval in peri menopausal women. AB - As part of a study on hormones and bone density in peri-menopausal women, metabolic clearance rates (MCR), and interconversions of androgens and estrogens and the peripheral aromatization of androgens were measured twice 2 yr apart. Measurements of clearance rates and interconversions were made from blood samples obtained during constant infusions of [3H]androgens and [14C]estrogens. Measurements of peripheral aromatization were made from the estrogen glucuronides in a pooled 4-day urine collection timed from the start of the infusions. The women were divided into 3 groups: Group A (n = 15) were having menstrual cycles throughout the 2 yr interval; Group B (n = 11) were having menstrual cycles at the time of Study 1 but had been amenorrheic for at least 1 yr at the time of Study 2; Group C (n = 28) were amenorrheic for at least 1 yr at the time of Study 1 and had remained amenorrheic through Study 2. The MCRs for testosterone, androstenedione, estrone and estradiol were not different for Study 1 and Study 2 in any of the groups. The interconversions of the androgens were similar in both studies for all groups. The conversion of estrone to estradiol decreased in Group A, otherwise the interconversions of the estrogens did not vary between the studies for the other groups. The peripheral aromatization of androstenedione, but not of testosterone, was significantly greater at study 2 compared to Study 1 for all groups. We conclude that the MCRs and interconversions of androgens and of estrogens are stable over time, but that the peripheral aromatization of androstenedione increases over a 2 yr interval. This increase may be menopausal and/or age related. PMID- 2308333 TI - Kinetic properties of the 5 alpha-reductase of testosterone in the purified myelin, in the subcortical white matter and in the cerebral cortex of the male rat brain. AB - The 5 alpha-reductase, the enzyme which converts testosterone into dihydrotestosterone (DHT), is present in several CNS structures of the rat. Recent reports from this laboratory indicate that the subcortical white matter and the myelin possess a 5 alpha-reductase activity several times higher than that present in the cerebral cortex. Moreover, previous ontogenetic observations indicate that in all cerebral tissues examined (including the myelin) the 5 alpha reductase has a higher activity in immature animals. This study was performed in order to verify whether the differences in the 5 alpha-reductase activity on the various brain components might be due to the presence of different concentrations of the same enzyme or to different isoenzymes. To this purpose, the kinetic properties Km and Vmax were measured in the purified myelin as well as in homogenates of the subcortical white matter and of the cerebral cortex, obtained from the brain of adult (60-90-day-old), immature (23-day-old), and aged (greater than 20-month-old) male rats. The results indicate that the enzymes present in the myelin, in the subcortical white matter and in the cerebral cortex of adult male rats possess a very similar apparent Km (1.93 +/- 0.2, 2.72 +/- 0.73 and 3.83 +/- 0.49 microM respectively). On the contrary, the Vmax values obtained in the myelin (34.40 +/- 5.54), in the white matter (19.57 +/- 2.36) and in the cerebral cortex (6.47 +/- 1.03 ng/h/mg protein) of adult animals have been found to be consistently different. Very similar Km values were found in the myelin obtained from the brain of immature and very old rats (2.14 +/- 0.11 and 3.39 +/- 0.75 microM respectively). The Vmax measured in the myelin purified from the immature rat brain (62.25 +/- 4.52) showed a value which was much higher than that found in the myelin of adult animals (34.40 +/- 5.54); a Vmax (34.31 +/- 9.41) almost identical to that of adult animals was found in the myelin prepared from the brain of aged rats. PMID- 2308334 TI - Differential regulation of DNA methylation in rat testis and its regulation by gonadotropic hormones. AB - Eukaryotic DNA methylation occurs exclusively at the 5'-position of cytosine and has been implicated in the regulation of gene expression. Using high-performance liquid chromatography, the methylation of testis DNA during its development, in different cell populations and during regulation by gonadotropic hormones, were studied. The 5-mC content of testis DNA increased significantly from days 30 to days 150, while in 2-yr-old testis 5-mC content decreased significantly. Among various populations of testicular cells, pachytene spermatocyte DNA contained a significantly high amount of 5-mC when compared to spermatogonia, spermatids and mature sperm DNA. However, the 5-mC content of elongated spermatids was significantly less when compared to the above four fractions. Administration of follicle stimulating hormone to immature rats caused hypomethylation of seminiferous tubular DNA while luteinizing hormone caused similar effects in Leydig cells. These results indicate that in testis, DNA methylation is differentially regulated during development and is controlled by gonadotropic hormones. PMID- 2308335 TI - [3H]DU41165: a high affinity ligand and novel photoaffinity labeling reagent for the progesterone receptor. AB - 17 alpha-Acetoxy-6-fluoro-16-methylene-(9 beta, 10 alpha)pregna-4,6-dien- 3,20 dione (DU41165), a retroprogestin (9 beta, 10 alpha) embodying a fluorine substituted dienone system, has been prepared in high specific activity tritium labeled form (4 Ci/mmol) and shown to be a high affinity ligand for the progesterone receptor (PgR) and a highly selective photoaffinity labeling reagent for PgR. The radiosynthesis involved conversion of DU41231 (the 17 alpha-hydroxy analog of DU41165) to DU41165 by treatment with tritium-labeled acetic anhydride. The binding affinity of DU41165 for PgR was determined by both a competitive binding assay and a direct binding assay (Scatchard analysis) to be 1.6-2.2-times higher than that of the high affinity synthetic progestin promegestone (R5020). In unlabeled form, DU41165 demonstrates photoinactivation of PgR to the extent of 60% at 60 min. In radiolabeled form [3H]DU41165 demonstrates specific covalent attachment with an efficiency of 5-7%. SDS-polyacrylamide gel electrophoresis of photoattached [3H]DU41165 confirms that there is covalent labeling of both the B subunit (Mr = 118,000), and the A subunit (Mr = 88,000) of PgR in a molar ratio of approximately 1:3. PMID- 2308336 TI - Synthesis of 1,25-dihydroxyvitamin D3 by spleen cells isolated from two patients with myelofibrosis and a normal subject. AB - The ability to synthesise [3H]1,25(OH)2D3 was studied in spleen cells incubated in short-term primary culture with [3H]25(OH)D3 which were isolated from two patients with idiopathic myelofibrosis and from one normal subject. Formation of a metabolite co-chromatographing with authentic 1,25(OH)2D3 on three different high-performance liquid chromatography systems was observed for cells from all three patients. [3H]1,25(OH)2D3 synthesis was 0.37 and 1.6 fmol/10(6) cells/incubation for cells with a density below that of lymphocyte separating media (1.077 g/ml) for the two myelofibrotic patients respectively and 0.15 fmol/10(6) cells/incubation for the normal subject. The most likely cell type capable of this synthesis were those of the monocyte-macrophage lineage which would have been present in abnormally high numbers in the patients with myelofibrosis. However, the exact identity of the cell-type responsible could not be determined because of the heterogeneity of cell types present. The observation that spleen cells from two patients with myelofibrosis and from a normal accident victim could metabolise [3H]25(OH)D3 to its active form [3H]1,25(OH)2D3 suggests a possible role for this metabolite in spleen haematopoiesis. PMID- 2308337 TI - Binding, X-ray and NMR studies of the three A-ring isomers of natural estradiol. AB - The effect of the position of the phenolic hydroxyl on the conformations of the three A-ring isomers of estradiol, namely, estra-1,3,5(10)-trien-1,17 beta-diol (10), estra-1,3,5(10)-trien-2,17 beta-diol (3), and estra-1,3,5(10)-trien-4,17 beta-diol (6), has been analyzed by X-ray crystallography. The results of these analyses were correlated with the absorptions of the angular methyl groups in the [1H]NMR spectra of these isomers and natural estradiol (E2). It was observed that the changes in chemical shift of protons at C18 corresponded to skeletal modifications in the steroid structure which changed the anisotropic effect of the hydroxyl group at C17. Examination of the affinity of these A-ring isomers of E2 for the estrogen receptor has shown the 2-hydroxylated isomer 3 to retain 1/5th the affinity of E2 for its binding protein. The 1- and 4-hydroxylated derivatives (10 and 6, respectively) bound to a much lesser extent. The receptor affinities of these estrogen analogues may be related to the angle between the 18 methyl and the 17 beta-hydroxyl groups (or the dihedral angle between the planar A-ring and the angular C18 methyl) as well as the position of the A-ring hydroxyl group. PMID- 2308338 TI - Wide spectrum of steroids serving as substrates for the formation of lipoidal derivatives in ZR-75-1 human breast cancer cells. AB - Recently, several natural steroids have been found to be esterified to long-chain fatty acids (FAE) in various mammalian tissues. The purpose of the present study was to determine the ability of a series of 3H-labeled steroids to serve as substrates for the formation and accumulation of such non-polar derivatives in intact cells, using the hormone-responsive ZR-75-1 human breast cancer cell line as model. All 14 steroids tested were found to be converted, directly or following further metabolism, to lipoidal ester derivatives. The percentage of intracellular steroids recovered as FAE derivatives was usually substantial (14 90%), especially in the case of C-19 steroids (75-90%). The composition of the lipoidal steroid fractions recovered from the labeled cell extracts was characterized by chromatographic comparison with synthetic steroid FAEs and by saponification of the steroid FAEs and identification of the released steroidal moieties. Following metabolism, most steroid substrates were converted into multiple lipoidal esters. Furthermore, 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstane-3 beta, 17 beta-diol, as well as androst-5-ene-3 beta, 17 beta diol formed lipoidal diesters in addition to the monoester form. The high level of intracellular steroid FAE accumulation reported in this study suggests that these yet poorly known steroid derivatives may play important functions in the regulation of steroid hormone metabolism and action. PMID- 2308339 TI - The influence of steroidal and nonsteroidal estrogens on the 5 alpha-reduction of testosterone by the ventral prostate of the rat. AB - The 5 alpha-reduction of testosterone to dihydrotestosterone (DHT) correlates with the androgen-mediated growth of the prostate under different experimental and clinical conditions. The aim was to study the regulation of the prostatic growth and enzyme activity by steroidal and nonsteroidal estrogens. Estrogens did not activate the androgen-dependent 5 alpha-reductase activity in cultured prostate of the rat. The direct inhibition of the enzyme activity by estrogens at the concentrations achievable in the male is not probable either. However, early estrogenization of the male rats in utero (on Day 17 of pregnancy) with diethylstilbestrol (DES) resulted in a persistent decrease of the enzyme activity and growth of the prostate indicating a critical estrogen-sensitive period in the regulation of the ultimate enzyme activity. The similar DES-like inhibitory effect on the growth of the prostate was achieved by keeping animals from fertilization throughout the pregnancy until weaning on diet containing soy, rich in environmental estrogens. Zearalenone (Zeranol) and coumestrol, two nonsteroidal estrogens found in human and animal food mimicked estradiol action in culture, but they were not estrogenic or antiestrogenic when administered to normal adults. PMID- 2308341 TI - In vitro metabolism of testosterone on hepatic tissue of chicken (Gallus domesticus). AB - Among the subcellular fractions of chicken liver homogenates, the microsomal and cytosol fractions were most active in metabolism of testosterone with mutually different enzymological features. On the other hand, the nuclear and mitochondrial fractions had far lower activity of metabolizing the steroid. Metabolism by the cytosol fraction: the following steroids were identified as the metabolites of testosterone. 5 beta-Dihydrotestosterone (17 beta-hydroxy-5 beta androstan-3-one), 5 beta-androstane-3 alpha,17 beta-diol and its 3 beta-epimer, 3 alpha-hydroxy-5 beta-androstan-17-one and its 3 beta-epimer and 5 beta androstanedione. Metabolism by the microsomal fraction: from testosterone under aerobic condition, androstenedione was obtained as the major metabolite, besides the minor polar metabolites, production of which diminished when incubated in the atmosphere of carbon monoxide. From the results, testosterone was accepted to be firstly converted by the cytosol fraction into 5 beta-dihydrotestosterone which was then reduced to 5 beta-androstane-3 alpha,17 beta-diol and its 3 beta-epimer. These diols were further converted partially to 3 alpha -and 3 beta-hydroxy-5 beta-androstan-17-ones. These pathways were supported by the results of our incubation study with 5 beta-dihydrotestosterone and 5 beta-androstanedione as substrates. By the microsomes, testosterone was aerobically and anaerobically transformed to androstenedione as the major metabolite. Throughout our incubation experiments, no 5 alpha-reduction of a delta 4-3-oxo-steroid was detected in the chicken liver. PMID- 2308340 TI - Relationship between adenohypophyseal and steroid hormones and variations in serum and urinary melatonin levels during the ovarian cycle, perimenopause and menopause in healthy women. AB - Morning levels of serum melatonin, FSH, LH, prolactin (PRL), progesterone and estradiol were studied by RIA during the ovarian cycle, perimenopause and menopause in 79 healthy women. FSH and LH levels showed a slight nonsignificant increase from the fertile period to perimenopause, exhibiting a significantly greater increase during menopause. PRL, progesterone and estradiol showed parallel changes, reaching lower levels during menopause. Serum melatonin levels decreased with age, attaining minimum levels in menopause. FSH and estradiol were significantly correlated with melatonin in the follicular phase, while in the luteal phase a negative correlation was found between melatonin, progesterone and estradiol. No significant correlations were noted between serum hormone levels during the perimenopausal period. In menopause, as during the follicular phase, melatonin and FSH were negatively correlated. As expected, a significant positive correlation was found between morning serum levels of melatonin and nocturnal urinary excretion of this indoleamine in all groups studied. PMID- 2308342 TI - Steroidogenesis in the testes and the adrenals of adult male rats after gamma irradiation in utero at late pregnancy. AB - Pregnant rats were irradiated with 2.1 Gy gamma-ray of 60Co at day 20 of gestation. Seventy days after birth, the body weight of the fetally irradiated male pups was significantly lower than the control. The testes, ventral prostates and seminal vesicles were atrophied by irradiation, whereas no decreased weight of the adrenals was observed. Histological examination of the testes of the irradiated rats revealed a complete disappearance of germinal cells. Sertoli cells and Leydig cells appeared normal, and no apparent histological difference was observed in the adrenals between the control and the irradiated rats. Activities of microsomal delta 5-3 beta-hydroxysteroid dehydrogenase (HSD) + isomerase, 17 alpha-hydroxylase/C17,20-lyase, 17 beta-HSD and 7 alpha-hydroxylase per pair of testes were decreased in the irradiated rats (36-86% of the control). In contrast, no decreased activity of 20 alpha-HSD in the cytosol fraction was observed by irradiation. No decreased activity of adrenocortical enzymes, such as delta 5-3 beta-HSD + isomerase, 21-hydroxylase, 11 beta-/18-hydroxylase and 5 alpha-reductase, was also observed in the irradiated group. Concentrations of LH, FSH, TSH, prolactin, testosterone, progesterone and aldosterone in serum were measured by radioimmunoassay. Only the FSH concentration was significantly increased by the irradiation, while no difference was found in the concentration of other hormones. It was concluded that irreversible damage was induced in spermatogenesis and androgen production by the fetal irradiation, whereas corticoidogenesis was not affected. PMID- 2308343 TI - Partial purification of androgen binding protein from bull epididymis. AB - An androgen binding protein (ABP), with an equilibrium dissociation constant of 4.2 nM and a molecular weight of about 100 kDa, has been purified from bull epididymal extracts using a four-step procedure. These preliminary results underline the main difficulties encountered in the purification of this protein present at a very low concentration (i.e. 50-fold less than in rat or rabbit epididymides). Ammonium sulfate precipitation is not a suitable step due to the formation, in presence of salt, of insoluble material leading to a loss of ABP. Lipids, particularly phospholipids, might be implicated in this phenomenon. Several steps, including anion exchange in batch followed by concentration, affinity chromatography and HPLC gel filtration allowed us to obtain a 7667-fold purified protein with a 9% yield. PMID- 2308344 TI - Protein binding of the contraceptive steroids gestodene, 3-keto-desogestrel and ethinylestradiol in human serum. AB - The protein binding of ethinylestradiol (EE2), gestodene (GEST) and 3-keto desogestrel (KDG) has been determined by ultrafiltration in the serum of women who had either taken a gestodene (n = 37) or desogestrel (n = 28) containing oral contraceptive for a time period of at least 3 months. GEST and KDG were analyzed in individual serum pools whereas EE2 was repeatedly measured in two serum pools, each one representing one treatment group. The respective free fractions of the three steroids were 0.6 +/- 0.1% (GEST), 2.5 +/- 0.2% (KDG), 1.7 +/- 0.6% (EE2, in the gestodene-group) and 1.5 +/- 0.2% (EE2, in the desogestrel-group). EE2 was exclusively bound to albumin, whereas GEST and KDG were also bound to sex-hormone binding globulin (SHBG). The distribution of the two progestins over the serum binding proteins was determined after heat-treatment of serum samples. For GEST, the contribution of albumin and SHBG was 24.1 +/- 9.1 and 75.3 +/- 9.1%, respectively and for KDG it was 65.9 +/- 11.9 and 31.6 +/- 12.0%, respectively. SHBG and corticosteroid-binding globulin (CBG) concentrations were measured in the serum samples obtained from both treatment groups. In the gestodene-group 180 +/- 61 nmol/l (SHBG) and 89 +/- 13 mg/l (CBG) were measured, the corresponding values in the desogestrel-group were 226 +/- 64 nmol/l (SHBG) and 93 +/- 14 mg/l (CBG). SHBG concentrations were correlated with the total concentration of GEST and its free fraction and a positive (r = 0.395) and negative (r = -0.491) correlation respectively was found. Only a weak negative correlation (r = -0.291) was found for SHBG and the free fraction of KDG in the serum. These data demonstrate that the three contraceptive steroids EE2, GEST and KDG were all bound extensively to serum proteins, however, with pronounced differences concerning their distribution over the various binding proteins. PMID- 2308345 TI - Coordinated induction of estrogen hydroxylase and catechol-O-methyl transferase by xenobiotics in first trimester human placental explants. AB - The estrogen phenol A-ring metabolism was investigated in the first trimester placenta using radioenzymatic techniques. In untested explants cultured for 16 h, estrogen hydroxylase (EH) but not catechol-O-methyl transferase (COMT) activity was increased significantly 1.8-fold (P less than 0.05). Cultures made in the presence of chemoprotectors, 25 microM of 1-phenylazo-2-naphthol (Sudan I) and coumarin but not 2(3)-tert-butyl-4-hydroxyanisole (BHA) caused a significant increase in EH activity, 1.8- and 2.2-fold, respectively (P less than 0.05). This was coupled with a significant, P less than 0.05, increase in the COMT activity by 25 microM of all three chemoprotectors, BHA, Sudan I, and coumarin, 2.7-, 2.3 , and 2-fold respectively. The carcinogens benzo(a)pyrene and 20 methylcholanthrene at 50 microM concentration, however, had no effect upon both enzymes' activity. Finally, the two enzymes's activities were correlated under the experimental conditions tested. Except for zero time where no correlation was found (r2 = 0.3), in all other experimental conditions, a significant (r2 = 0.75) correlation was observed. In conclusion, EH and COMT enzyme activities appear to undergo a coordinated induction in cultured placental explants in the first trimester. The implications of catechol metabolism for embryonal development are discussed. PMID- 2308346 TI - Measurement of ethanol in the human brain using NMR spectroscopy. AB - Ethanol in the human brain is readily observable by noninvasive 1H NMR spectroscopy. We have made such observations in a human subject with a time resolution per measurement of 6.5 min and volume resolution of 16 cc. The ethanol methyl proton signal is well separated from signals of other metabolites in 1H spectra from human brain and it is one of the most intense signals in such spectra when blood ethanol concentration is 0.1% (21.7 mM)--the legal definition of alcoholic intoxication in many jurisdictions. These properties, plus the fact that the ethanol signal can be further isolated from other resonances by spectral editing, open several possibilities for further investigation. PMID- 2308347 TI - Effect of alcohol on sensory and sensorimotor visual functions. AB - The literature on the effect of alcohol on sensory and sensorimotor visual functions is extensive. The findings are often contradictory and early studies did not correlate the effects with blood alcohol levels. This study was designed to test the effects of alcohol on various visual functions using equipment that is freely available to the clinician. A significant loss of visual field, accommodation and convergence that correlated with increasing blood alcohol levels was found. Visual acuity, color vision and stereoacuity were not significantly altered by alcohol. PMID- 2308348 TI - Acute alcohol intoxication and cognitive functioning. AB - Acute alcohol intoxication produces changes in the cognitive functioning of normal individuals. These changes appear similar prima facie to those exhibited by individuals who sustain prefrontal lobe damage during adulthood. In order to test the validity of this observation, and to control for the confounding effects of expectancy, 72 male subjects were administered a battery of neuropsychological tests, within the context of a balanced-placebo design. Each subject received one of three widely different doses of alcohol. Analysis of the results of the cognitive test battery demonstrated that a high dose of alcohol detrimentally affects a number of functions associated with the prefrontal and temporal lobes, including planning, verbal fluency, memory and complex motor control. Expectancy does not appear to play a significant role in determining this effect. The implications of this pattern of impairment are analyzed and discussed. PMID- 2308349 TI - Male and female differences in liver cirrhosis mortality in the United States, 1961-1985. AB - Changes in the social roles of American women have led to questions about convergence in drinking practices and alcohol-related problems between men and women. To address this issue, we utilized mortality data for liver cirrhosis derived from United States death certificates for the years 1961 to 1985. Using age-adjusted rates, we found no evidence of a major shift toward convergence in cirrhosis mortality over this time period for the total population. When age specific rates were examined, we found evidence for increasing divergence in liver cirrhosis mortality rates for those under the age of 55, whereas the general trend among the older age groups was toward convergence. Straightforward interpretation of the results is hampered by the lack of research in related areas, but the findings do suggest that greater public and professional education may serve a preventive purpose for older U.S. females. PMID- 2308350 TI - Alcoholism and smoking. AB - A case-control study compared the natural history of cigarette smoking in alcoholic and nonalcoholic populations to determine why alcoholism and smoking are closely associated. Eighty-three percent of alcoholics were smokers compared to 34% of the nonalcoholic subjects. Compared to other children, children who later became alcoholic were more likely to become regular users of tobacco once they had tried it. Only 7% of alcoholic smokers were successful in their attempts to quit smoking compared to 49% of the nonalcoholic smokers. More research comparing the smoking cessation efforts of alcoholics and nonalcoholics is needed to confirm these findings. Alcoholism is estimated to be 10 times more common among smokers than among nonsmokers. Possible explanations for this include a susceptibility on the part of some individuals to addictive drugs in general, and/or for some individuals tobacco smoking and alcoholism are both sequelae of a propensity to behave irresponsibly. PMID- 2308351 TI - Bad drivers: identification of a target group for alcohol-related prevention and early intervention. AB - Individuals arrested for driving while intoxicated (DWI) have been targeted for preventive intervention of alcohol-related problems. However, high rates of diagnosed alcoholism among DWI arrestees suggest a need to identify individuals at risk earlier in the developmental process. The present study investigates one such group, namely male "bad drivers" with a history of multiple nonalcohol related driving convictions. Over 11% of a sample of 254 men identified as bad drivers during an index year received an initial DWI arrest over a subsequent 3 year follow-up period. This was over five times greater than the rate of initial DWI arrest among a representative sample of men from the general driving population over the same time period. The same high rate of subsequent DWI arrest among drivers having four or more driving offenses within the index year was replicated in a 1% probability sample of over 39,000 drivers from the general driving population. Those individuals from the original group of 254 bad drivers who received an initial DWI had significantly higher levels of drinking at the time of their original identification as bad drivers than did those who did not receive a DWI. The results were discussed in terms of early identification and preventive interventions within the population of bad drivers. PMID- 2308352 TI - Personality characteristics of sons of alcohol abusers. AB - Studies of personality characteristics of sons of alcohol abusers who are at high risk for alcoholism have yielded equivocal results. Although differences in personality attributes have been identified in clinical samples, similar differences have not been found in nonclinical samples, raising the possibility that these dispositional differences do not characterize the majority of offspring of alcoholics. This study investigated personality characteristics of sons of alcohol abusers (n = 199) and controls (n = 601) in a nonclinical sample of college-aged men. Analyses revealed that scores of sons of alcohol abusers differed significantly from controls on all 10 Clinical scales and 7 of 13 Wiggins Content scales of the Minnesota Multiphasic Personality Inventory. Replicating earlier studies with clinically identified male offspring of alcoholics, these results show that parental alcohol abuse is related to reliable but relatively small elevations of MMPI personality profiles in well-functioning sons of alcohol abusers. PMID- 2308353 TI - The structure of depression in alcoholic women. AB - This study examines depression that is manifest at the time of an alcoholic woman's admission to treatment by describing indices of depression that were constructed by submitting interview items to factor analysis. Alcoholic women (N = 301) and nonalcoholic women (N = 137), who served as controls, responded to 48 depression items taken from several interview schedules, including the Diagnostic Interview Schedule, the Center for Epidemiological Studies Depression Scale and the Personal Attributes Questionnaire. These 48 items were submitted to exploratory principal components analysis. Four factors, Current Mood, Low Self Esteem, Negative Perceptions of Childhood and Somatic Symptoms emerged in the rotated solution, with coefficient alphas ranging from .83 to .92. Internal reliabilities for the depression indices remained sufficiently high across age and sample subgroups, suggesting that the structure of alcohol-induced depression in women does not differ from depression in nonalcoholic control women. PMID- 2308354 TI - Labeling the child of an alcoholic: negative stereotyping by mental health professionals and peers. AB - Although the establishment of programs for children of alcoholics (COAs) is laudable for those who are in distress, the effects of identifying and labeling COAs have largely been unknown. These studies investigated the possibility of negative stereotypes toward COAs emanating from peers and from the mental health community. In Study 1, 570 high school students were asked to rate six separate roles (typical teenagers--male and female; teenagers with an alcoholic parent- male and female; and mentally ill teenagers--male and female) using 11 bipolar adjective pairs. Subjects rated "COAs" as significantly different overall from both "typical teenagers" and "mentally ill teenagers." When individual nonsignificant differences occurred, COAs were more often grouped with mentally ill teenagers. These correlational findings were extended in an experimental study (Study 2) using mental health workers (N = 80). Subjects watched videotapes of an adolescent who was described as having either a positive or negative family history of alcoholism and as having either a high degree of social success (school leader) or social problems (behavior problems). The adolescent targets labeled COA were judged as more pathological than those labeled non-COA in terms of current and predicted psychological health and psychopathology. These judgments held regardless of the teenagers' labeled current behavior. Both studies demonstrated robust negative stereotypes about COAs both from the COAs' peers and from those responsible for treating COAs. The potentially harmful consequences of labeling COAs--especially those who are currently well-adjusted- are discussed. PMID- 2308355 TI - Additive independent factors that predict risk for alcoholism. AB - Pedigree and adoption studies have supported a genetic heterogeneity model for alcoholism. Lifetime alcoholism diagnosis in medical-surgical inpatients was reported to increase additively with the presence of Antisocial Personality Disorder (ASP) diagnosis, male gender and family history of alcoholism (FHA). These three risk factors have been shown to have separate genetic transmission. This study tested the predictive strength of these factors in a prospective sample of untreated, nonhospitalized young male (n = 98, mean = 25.2 years) and female (n = 121, mean = 25.5 years) offspring of alcoholic (n = 131) and nonalcoholic (n = 88) parents. NIMH-Diagnostic Interview Schedule items were used to diagnose blindly DSM-III alcohol or drug abuse or dependence. No alcohol- or drug-related behavioral items were used in ASP diagnosis. Parental alcoholism was rated using proband information and Family History Research Diagnostic Criteria. ASP, then gender and finally FHA but not age were significant predictors of DSM III alcoholism. The log linear analysis improvement chi square was significant at p less than .05 for each variable and the overall goodness of fit of the model was substantial (chi 2 = 13.3, p = .78). Prediction of lifetime alcohol abuse/dependence rates for young adults in a prospective sample was highly significant. These three factors with separate genetic vulnerability increased risk over a lifetime. Male gender increased the risk for alcoholism 1.5 times, FHA 1.5 times and ASP diagnosis 3 times in an independent and additive manner. PMID- 2308356 TI - The relation of alcohol expectancies to drinking patterns among alcoholics: generalization across gender and race. AB - Results of laboratory and psychometric research indicate that beliefs about the behavioral effects of alcohol are related to patterns of alcohol use and abuse. These findings also suggest that expectancy-drinking behavior associations are moderated by several variables, such as gender. The purpose of this study was to determine whether the correspondence of alcohol-related expectancies and drinking patterns was different for black and white men and women undergoing residential treatment for alcoholism using a hierarchical multiple regression algorithm. Relatively few gender- or race-specific expectancy-drinking behavior relations were found, and most of these were identified for beliefs that alcohol enhances sexuality and induces relaxation. Expectations that alcohol improves sociability and elevates mood were the best predictors of multiple, negative drinking-related consequences of drinking for all subjects. PMID- 2308357 TI - The use of extracorporeal circulation for circulatory support during PTCA. PMID- 2308358 TI - Primary repair of tetralogy of Fallot in infancy. AB - From June 1983 to April 1988, 100 consecutive infants with symptomatic tetralogy of Fallot (without pulmonary atresia) were operated on. Ages ranged from 0.5 to 12 months (mean 7.3 +/- 3.7). Twenty patients were 0.5 to 3 months, 21 were 3 to 6 months, and 59 were 6 to 12 months of age. Mean weight was 6.5 kg +/- 1.7. Seventy patients received a transannular patch. The hospital mortality rate was 3% and there were no late deaths. Cumulative follow-up was 180 patient-years. Causes of death included hypoplastic pulmonary arteries (4 and 5 months old) and right ventricular failure (4 months old). The most important factors influencing right ventricular outflow tract reconstruction were neither weight (p = 0.90) nor age (p = 0.05) but rather were the ratio between weight and pulmonary arterial outflow tract diameter (p = 0.0005) and the ratio between body surface area and pulmonary arterial outflow tract diameter (p less than 0.0001). The last 48 patients were operated on with no deaths. During this period, operative management differed essentially in myocardial protection with blood cardioplegia. The predicted 30-day survivorship after repair was 90% to 99% (95% confidence limits). No ventricular arrhythmias have been detected after repair (mean follow up 22.2 months). Mean right ventricular/left ventricular end-diastolic dimension ratio was (0.53 +/- 0.10 with M-mode echocardiography. These early results encourage us to proceed with primary repair of infants with symptomatic tetralogy of Fallot thanks to improved surgical management and enhanced myocardial protection. PMID- 2308359 TI - A new technique for one-stage radical eradication of long-standing chronic thoracic empyema. AB - The surgical treatment of chronic long-standing thoracic empyema remains a challenging subject. A simple technique that consumes less operative time, accompanying less bleeding, and that enables eradication of the disease in one stage was devised by the senior author. The technique requires only three major steps: (1) decortication limited to the parietal sides of the peel's sac, (2) cleansing the empyemic cavity, and (3) drainage. To date, six patients have been treated by this method; complete cure was achieved in all. Neither death nor recurrence of the disease has been noted during the follow-up period averaging 24.5 months. The mean operative time was 3.06 hours, mean bleeding volume was 1262 ml, and the mean hospital stay period was 1.14 months. The methods and results of the technique are discussed. PMID- 2308360 TI - Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. III. Long-term changes and their modification by platelet inhibition with aspirin and dipyridamole. AB - The objectives of this study were to elucidate the long-term influence on vein bypass grafts of platelet inhibition and its late discontinuation. Cephalic vein grafts were interposed bilaterally in the femoral arteries of stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Fifteen animals were divided into three groups of five animals each. Group I received no medications and served as a control group. Group II received for the full duration of the study a combination of aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Group III received the same regimen of platelet inhibition as in group II during the first 9 months, but were not treated during the subsequent 9-month interval. Grafts were excised for analysis from groups I and II at both 9 and 18 months and from group III at 18 months. Cholesterol content in group I grafts was 470 +/- 89 micrograms/100 mg at 9 months and 388 +/- 127 micrograms/100 mg at 18 months. In group II grafts, cholesterol content was 208 +/- 72 micrograms/100 mg at 9 months (p less than 0.001 compared with group I) and 266 +/- 84 micrograms/100 mg at 18 months. In group III grafts, cholesterol content was 249 +/- 71 micrograms/100 mg at 18 months. Differences in cholesterol content among the three groups of grafts at 18 months were not found to be statistically significant. Stepwise regression analysis at 18 months showed that cholesterol content was best predicted by medial fibrosis (r2 = 0.66) followed by abundance of foam cells (increase in r2 = 0.26) in group I, by fibrin in group II (r2 = 0.63), and by prevalence of macrophages in group III (r2 = 0.74). In all groups, platelets, fibrin, and polymorphonuclear leukocytes were less abundant than they had been at 3 months. Cross-sectional area occupied by the intima was not influenced by platelet inhibition. PMID- 2308362 TI - Perinodal cryosurgery for atrioventricular node reentry tachycardia in 23 patients. AB - Atrioventricular node reentry tachycardia is the most common cause of paroxysmal supraventricular tachycardia. Available nonpharmacologic therapies include (1) catheter ablation or cryosurgical ablation of the His bundle and insertion of a permanent pacemaker and (2) surgical dissection around the atrioventricular node or discrete cryosurgery of the perinodal tissues, in an attempt to divide or ablate only one of the dual atrioventricular node conduction pathways responsible for the tachycardia while leaving the other intact. This report describes 23 consecutive patients who underwent the discrete cryosurgical procedure between August 13, 1982, and March 16, 1989. The first patient in this series, a 38-year old woman, is the first patient in whom refractory atrioventricular node reentry tachycardia was cured surgically by a procedure designed to treat this arrhythmia. The ages of the 13 female and 10 male patients ranged from 12 to 56 years with an average age of 29 years. Fourteen of the 23 patients (61%) had the Wolff-Parkinson-White syndrome. Other associated arrhythmias included atrial flutter/fibrillation (n = 2), right atrial reentrant tachycardia (n = 1), junctional tachycardia (n = 1), and a Mahaim fiber (n = 1). Associated anatomic abnormalities included Ebstein's anomaly in two patients and a large right atrial aneurysm in one patient. The perinodal cryosurgical procedure was performed through a right atriotomy in the normothermic beating heart. Multiple 3 mm diameter cryolesions were placed around the borders of the triangle of Koch on the lower right atrial septum to alter the input pathways of the atrioventricular node. There were no operative deaths in this series of patients. Postoperatively, all 23 patients had normal atrioventricular conduction, and no heart block has occurred in any patients during the follow-up period. All patients have remained free of atrioventricular node reentry tachycardia (and of the Wolff-Parkinson White syndrome) and none has required postoperative antiarrhythmic drugs for either of these arrhythmias. We consider this simple, safe, easily performed, and uniformly successful operation to be the procedure of choice for the treatment of medically refractory atrioventricular node reentry tachycardia. PMID- 2308361 TI - Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts. AB - A pig model of autologous saphenous vein to common carotid artery bypass grafting was developed. An end-to-end anastomotic technique led to lower middle graft and distal turbulence. Saphenous veins were surgically prepared with or without distention at 600 mm Hg, implanted into the arterial circulation, and removed 2 hours later. Medial integrity was then assessed by adenosine triphosphate/adenosine diphosphate concentration ratio, and endothelial integrity, leukocyte and platelet adhesion by scanning electron microscopy. In grafts made with undistended vein adenosine triphosphate/adenosine diphosphate concentration ratio was not significantly lower (3.0 +/- 0.1, n = 32) than in freshly isolated vein (3.3 +/- 0.1, n = 26), endothelial cover was 98% +/- 1%, n = 6, and there was little platelet or leukocyte adhesion. In distended grafts adenosine triphosphate/adenosine diphosphate concentration ratio was reduced to 2.2 +/- 0.2 (n = 7, p less than 0.005), endothelial cover was reduced to 38% +/- 14% (n = 6, p less than 0.001), and there was extensive platelet and leukocyte adhesion to exposed subendothelium. In separate experiments graft patency measured at 1 to 5 weeks was significantly greater (96%, n = 25) when undistended vein was used than when distended vein was used (64%, n = 25, p less than 0.005). The data show that distention leads to medial and endothelial damage and that this is associated with increased platelet and leukocyte adhesion and with reduced early patency. PMID- 2308363 TI - Role of lung biopsy in patients undergoing a modified Fontan procedure. AB - Fifty-six patients undergoing a modified Fontan procedure from 1977 to 1985 had lung tissue available from the perioperative period (n = 51) or recent palliative procedure (n = 5) (37 biopsy, 12 autopsy, 7 biopsy and autopsy). Twenty-six patients had tricuspid atresia, and 30 had other causes of functional univentricular heart. Pulmonary arterial structure was classified by both the Heath-Edwards and morphometric scales. Biopsy and autopsy grades were identical except for a minor difference in Heath-Edwards scale in one case. Elevated preoperative mean pulmonary artery pressure (greater than 15 mm Hg) was associated with medial hypertrophy (p = 0.04), although six patients with normal pulmonary artery pressure had medial hypertrophy and six patients with mean pulmonary artery pressure greater than 15 mm Hg did not have medial hypertrophy. Medial hypertrophy was a possible risk factor in patients with univentricular heart: Patients with medial hypertrophy had a ninefold greater risk of death (p = 0.08). Controlling for confounding variables did not alter this result (0.06 less than or equal to p less than or equal to 0.10). Medial hypertrophy was not a risk factor for death in patients with tricuspid atresia: Four had this feature and each survived. Four patients with tricuspid atresia died and none had medial hypertrophy. A mean transpulmonary pressure gradient was measured on the first postoperative day in 45 patients. In patients with medial hypertrophy there was a trend toward a higher gradient (p = 0.13). All patients with medial hypertrophy who had this measurement (n = 9) had a transpulmonary pressure gradient of 7 mm Hg or greater, whereas this was true in only 18 of 36 without medial hypertrophy (p = 0.007). On the basis of an evaluation of medial hypertrophy, we conclude that biopsy does not aid in selection of patients with tricuspid atresia for a Fontan procedure; its role in patients with univentricular heart is uncertain. PMID- 2308364 TI - Augmenting intracellular adenosine improves myocardial recovery. AB - The objective of this study was to determine if augmentation of myocardial adenosine levels during global ischemia improves functional recovery after reperfusion. Isolated adult rabbit hearts were subjected to 120 minutes of mildly hypothermic ischemia (34 degrees C) with modified St. Thomas' Hospital cardioplegic solution used to provide myocardial protection. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegic solution or by inhibiting adenosine degradation with 2 deoxycoformycin, a noncompetitive inhibitor of adenosine deaminase. Four groups of hearts were studied: (1) control (n = 23)--cardioplegia alone; (2) adenosine group (n = 10)--adenosine 200 mumol/L added to the cardioplegic solution; (3) 2 deoxycoformycin group (n = 8)--2-deoxycoformycin 1 mumol/L added to the cardioplegic solution; and (4) a combined adenosine/deoxycoformycin group (n = 10). Recovery of developed pressure 45 minutes after reperfusion in the control group averaged only 38% +/- 4% of baseline values. Significantly better recovery was evident in the adenosine (66% +/- 7%), deoxycoformycin (59% +/- 2%), and adenosine/deoxycoformycin (75% +/- 2%) groups. The slope of the relationship between end-diastolic pressure and volume was used as an index of diastolic stiffness. The slope averaged 85 +/- 2 mm Hg/ml in the control group 45 minutes after reperfusion, significantly higher than that in the adenosine (31 +/- 6), deoxycoformycin (75 +/- 5), and adenosine/deoxycoformycin (58 +/- 5) groups; this suggests better diastolic function in the adenosine-augmented groups. During ischemia, adenosine levels were significantly elevated in the adenosine-augmented groups, whereas adenosine triphosphate decreased equally in all four groups, which indicates that augmenting myocardial adenosine had no effect on depletion of adenosine triphosphate during ischemia. After reperfusion, adenosine triphosphate levels were depressed in the control group but increased in the other groups above baseline values, which suggests that improvement in functional recovery was due to accelerated repletion of adenine nucleotide stores in the adenosine-augmented groups. PMID- 2308365 TI - Calcium paradox in an in vivo model of multidose cardioplegia and moderate hypothermia. Prevention with diltiazem or trace calcium levels. AB - The production and prevention of calcium paradox injury in myocardium was studied in a canine model of cardiopulmonary bypass with multidose, moderately hypothermic, crystalloid cardioplegic solution. During 4 1/2 hours of global ischemia, three groups of six dogs each received one of three histidine-buffered cardioplegic solutions (500 ml initially and 250 ml every 30 minutes) at 27 degrees C. Group 1 cardioplegic solution was calcium free, group 2 solution contained a trace amount of calcium chloride (70 mumols /L), and group 3 cardioplegic solution was calcium free but contained diltiazem (150 micrograms/kg body weight). Left ventricular function measured as percent control of developed pressure revealed significantly greater (p less than 0.05) recovery in groups 2 and 3. Triphenyltetrazolium chloride staining showed 35% +/- 9% (mean +/- standard error) of heart mass necrosis in group 1 versus 0% and 0.5% +/- 0.4% in groups 2 and 3, respectively (p less than 0.001). Electron microscopy revealed ultrastructural changes characteristic of calcium paradox injury in group 1 myocardium. Calcium paradox injury was produced in an in vivo model of global myocardial ischemia and multidose cardioplegia despite moderate hypothermia and non-coronary collateral flow. The addition of either trace levels of calcium or diltiazem to the cardioplegic solution was effective in preventing this injury. PMID- 2308366 TI - Orthotopic heart transplantation for complex congenital heart disease. AB - Orthotopic heart transplantation has become standard therapy for end-stage cardiomyopathy in children and adults, but there has been much less experience with transplantation for complex congenital heart disease. In this report experience with orthotopic transplantation in seven children with various forms of complex congenital heart disease is reviewed. Diagnoses included hypoplastic left heart syndrome in two (after stage I palliation), left ventricular diverticulum in one, single ventricle in two (dextrocardia, atrial situs inversus, and total anomalous pulmonary venous return in one patient and post Fontan repair in the second), D-transposition of the great arteries and ventricular septal defect (post-Senning repair and ventricular septal defect closure) in one, and Ebstein's anomaly with biventricular dysplasia in one. Six of the seven were hospital survivors and there has been one late death at 2 1/3 years. Modifications of the standard operative technique to fit the anatomic variations in these defects are reviewed. PMID- 2308367 TI - Cardiac transplantation in situs inversus. AB - Transplantation of the heart was successfully performed in a patient with situs inversus of the viscera and atria. Anatomic constants common to all patients allowed the left atrium, pulmonary artery, and aorta to be joined as usual in the transplant operation. Systemic venous reconstruction was the crux of the operation. A composite superior vena cava was reconstructed on the right side from the recipient translocated superior vena cava, donor superior vena cava and innominate vein, and recipient in situ pericardium. The inferior vena cava was rerouted from the left side across the midline to the right through a composite conduit consisting of the recipient night atrium and in situ pericardium over the diaphragm. These reconstructed venous passageways have remained patent and unobstructed for 1 1/2 years after the operation. PMID- 2308368 TI - Eight-year results of cyclosporine-treated patients with cardiac transplants. AB - To elucidate the long-term effects of cyclosporine, we retrospectively studied 310 consecutive patients who have undergone cardiac transplantation at our institution since December 1980 and in whom immunosuppression has been maintained with cyclosporine. The ages of recipients ranged from 1 month to 64 years and of donors from 1 month to 48 years. The actuarial survival rates for cyclosporine treated patients were 80.7% at 1 year and 59.7% at 5 years and were significantly greater than those for previous patients not treated with cyclosporine (p less than 0.005). Their actuarial prevalence of rejection was 60.0% at 1 month and 86.9% at 1 year; 206 patients are living. The actuarial prevalence of lymphoma development was 4.6% at 5 years but has been significantly lower with the current immunosuppression protocol of lower doses of cyclosporine, and OKT3 in place of rabbit anti-thymocyte globulin (p less than 0.005). Infection remains the most common cause of death. Recipients less than 50 years of age had a significantly higher actuarial survival than older recipients (p less than 0.01). Male and female recipients had similar overall prevalence of survival and rejection, but men died of graft atherosclerosis significantly more frequently (p less than 0.005). Rehabilitation has been successful in 85% of patients surviving 1 year after transplantation. Of those surviving 1 year, 96.5% were in New York Heart Association class I. Thus the results of orthotopic cardiac transplantation have improved since the introduction of cyclosporine and have allowed measured liberalization of the criteria for recipient selection. PMID- 2308370 TI - Heparin dosing and monitoring for cardiopulmonary bypass. A comparison of techniques with measurement of subclinical plasma coagulation. AB - Subclinical plasma coagulation during cardiopulmonary bypass has been associated with marked platelet and clotting factor consumption in monkeys. To better define subclinical coagulation in man, we measured plasma fibrinopeptide A concentrations before, during, and after cardiopulmonary bypass. Patients were assigned to one of three groups of heparin management: group 1 (n = 10)--initial heparin dose 300 IU/kg, with supplemental heparin if the activated coagulation time fell below 400 seconds; group 2 (n = 6)--initial heparin dose 250 IU/kg, with supplemental heparin if activated coagulation time was less than 400 seconds; and group 3 (n = 5)--initial heparin dose 350 to 400 IU/kg, with supplemental heparin if whole blood heparin concentration was less than or equal to 4.1 IU/ml. Activated coagulation time and heparin concentration were measured every 30 minutes during cardiopulmonary bypass, and fibrinopeptide A was measured at hypothermia, normothermia, and whenever activated coagulation time was less than 400 seconds. Quantitative and qualitative blood clotting competence was assessed after cardiopulmonary bypass, including mediastinal drainage for the first 24 hours. Fibrinopeptide A values were markedly elevated during cardiopulmonary bypass but were well below the levels present before and after cardiopulmonary bypass. Fibrinopeptide A correlated inversely with heparin concentration during cardiopulmonary bypass (r = -0.46, p = 0.03), but higher fibrinopeptide A levels during cardiopulmonary bypass did not correlate with post cardiopulmonary bypass coagulopathy. Group 3 patients received the highest heparin doses (p less than 0.05) and had the greatest postoperative blood loss (p less than 0.05). Protamine dose and heparin concentration during cardiopulmonary bypass correlated best with postoperative mediastinal drainage. Our findings support the following conclusions: (1) compensated subclinical plasma coagulation activity occurs during cardiopulmonary bypass despite activated coagulation time greater than 400 seconds or heparin concentration greater than or equal to 4.1 IU/ml; (2) post-cardiopulmonary bypass mediastinal drainage correlates strongly with increased heparin concentration during cardiopulmonary bypass (p less than 0.05) and protamine dose (p less than 0.05); and (3) during cardiopulmonary bypass at both normothermia and hypothermia, activated coagulation times greater than 350 seconds result in acceptable fibrinopeptide A levels and post cardiopulmonary bypass blood clotting. PMID- 2308369 TI - L-aspartate improves the functional recovery of explanted hearts stored in St. Thomas' Hospital cardioplegic solution at 4 degrees C. AB - Explanted rat hearts were subjected to cardioplegic arrest by 3 minutes' perfusion with oxygenated St. Thomas' Hospital solution no. 2 and then were stored by immersion in the same solution at 4 degrees C. Prearrest and postischemic left ventricular functions were compared by means of an isolated working heart apparatus. Hearts (n = 8 per group) arrested and stored for up to 8 hours all resumed the spontaneous rhythm of contraction during reperfusion for 30 minutes at 37 degrees C. There was good recovery of aortic flow rate (105% +/- 3%) against a pressure of 100 cm H2O, of heart rate (102% +/- 2%), and of aortic pressure (86% +/- 5% of prearrest values). Hearts stored for 10 and 20 hours showed poor or no postischemic recovery of cardiac pump function (aortic flow, 16% +/- 11% and 0%, respectively). Enrichment of St. Thomas' Hospital solution with L-glutamate (20 mmol/L) also failed to improve functional recovery of hearts subjected to 10 hours of storage, but hearts treated with St. Thomas' Hospital solution containing L-aspartate (20 mmol/L) or L-aspartate plus L-glutamate (20 mmol/L each) reestablished aortic flow rates of 99% +/- 5% and 93% +/- 4%, respectively. These results indicate that the addition of L-aspartate to St. Thomas' Hospital solution improves the functional recovery and extends the safe preservation of explanted hearts stored at 4 degrees C. PMID- 2308371 TI - Further morphologic studies on tetralogy of Fallot, with particular emphasis on the prevalence and structure of the membranous flap. AB - We have investigated 158 hearts from patients with tetralogy Fallot so as to probe the precise anatomy of so-called membranous flaps and their relationship to the ventricular septal defect, the tricuspid valve, and the atrioventricular conduction axis. A membranous flap was detected in 61 hearts (38.6%) of the 158, all being found when the ventricular septal defect was perimembranous. Two types of flap were discovered. A remnant of the interventricular membranous septum (or a real flap) was seen in 32 and reduplication of the leaflets of the tricuspid valve (pseudoflap) was present in 32. The pseudoflaps either were connected to the anteroseptal commissure of the tricuspid valve or were attached to the medial papillary muscle complex. The medial papillary muscle was abnormally attached more frequently in those hearts with flaps (31%, 52%) than in the ones lacking a flap (5%) (p less than 0.01). An anomalous arrangement of the leaflet of the tricuspid valve was significantly more prevalent in those hearts with a pseudoflap (41%) than in those with a real flap (14%) and in those without a flap (9%). There was a tendency for real flaps to be smaller (p less than 0.05) and thinner than pseudoflaps. A few flaps were considered too tiny to warrant placement of sutures within their structure during surgical repair. During our investigation, we noted also the morphologic arrangement of the rest of the hearts. PMID- 2308372 TI - Intraoperative perfusion contrast echocardiography. Initial experience during coronary artery bypass grafting. AB - Intraoperative evaluation of the effectiveness of myocardial revascularization has been limited by an inability to assess regional myocardial perfusion. Microbubbles of sonicated diatrizoate sodium and diatrizoate meglumine (Renografin) have been an effective echocardiographic contrast agent and have been employed clinically during cardiac catheterization. This recent development in contrast-enhanced two-dimensional echocardiography permits real-time imaging of transmural myocardial blood flow but has not been evaluated in the operating room. This study represents the initial surgical application of this directed technique and was designed to evaluate the safety and efficacy of intraoperative perfusion contrast echocardiography in assessing the results of coronary artery bypass grafting. Twenty men with significant coronary artery disease ranging in age from 49 to 73 years were studied. Direct contrast agent injection into completed saphenous vein bypass grafts caused the myocardium supplied by each graft to be well delineated and provided a tomographic view of contrast distribution. The enhanced region was well correlated with the size and distribution of the native vessel. Rapid contrast washout (less than 20 seconds) indicated satisfactory regional perfusion. Contrast echocardiography prolonged the operation less than 10 minutes and did not result in any perioperative complications. PMID- 2308373 TI - The Carpentier-Edwards standard porcine bioprosthesis. A first-generation tissue valve with excellent long-term clinical performance. AB - The Carpentier-Edwards standard porcine bioprosthesis was implanted in 1190 patients (1201 operations, 1303 valves) between January 1975 and June 1986; most implants were before 1982. The mean age of the patients was 57.2 years (range 8 to 85 years). The early mortality was 7.6% (aortic valve replacement 5.1%, mitral valve replacement 8.8%, and multiple valve replacement 15.3%). Late mortality was 3.9% per patient-year (aortic valve replacement 3.6%, mitral valve replacement 4.2%, and multiple valve replacement 3.8%). The total cumulative follow-up period was 6737 years. Thromboembolism was 1.5% per patient-year (fatal 0.4% per patient year) (minor 0.6%, major 0.9%); antithromboembolic therapy-related hemorrhage was 0.5% (fatal 0.1%); prosthetic valve endocarditis was 0.6% (fatal 0.2%); nonstructural dysfunction was 0.5% (fatal 0.2%); and structural valve deterioration and/or primary tissue failure was 1.5% per patient-year (fatal, 0.2% per patient-year). Thromboembolism and structural valve deterioration were the significant complications, structural valve deterioration occurring primarily between the sixth and 10th year of evaluation. The overall patient survival was 65.0% for aortic valve replacement and 54.8% for mitral valve replacement (p less than 0.05) at 10 years. The patients were classified as 92.9% New York Heart Association functional classes III and IV preoperatively and 92.3% classes I and II postoperatively. Freedom at 10 years from thromboembolism was 84.3% for aortic valve replacement and 76.5% for mitral valve replacement (p = 0.05); structural valve deterioration was 78.6% for aortic valve replacement and 71.6% for mitral valve replacement (p less than 0.05); reoperation was 74.4% for aortic valve replacement and 67.1% for mitral valve replacement (p less than 0.05). Freedom from all valve-related complications at 10 years was 58.9% for aortic valve replacement and 46.8% for mitral valve replacement (p less than 0.05); valve related mortality was 89.5% for aortic valve replacement and 82.6% for mitral valve replacement (p = not significant); mortality and reoperation was 58.9% for aortic valve replacement and 46.8% for mitral valve replacement (p less than 0.05); mortality and residual morbidity (treatment failure) was 87.2% for aortic valve replacement and 75.1% for mitral valve replacement (p = not significant); mortality, residual morbidity, and reoperation were 66.3% for aortic valve replacement and 54.9% for mitral valve replacement (p less than 0.05). The standard Carpentier-Edwards porcine bioprosthesis has provided satisfactory clinical performance and has afforded patients excellent quality of life. PMID- 2308374 TI - Malignant primary pulmonary paraganglioma with hilar metastasis. PMID- 2308376 TI - Total cavopulmonary connection. PMID- 2308375 TI - Limb ischemia induced by intraaortic balloon pumping. PMID- 2308377 TI - Fiberoptic intracranial pressure monitoring in rats. AB - An adaptation of a fiberoptic intracranial pressure monitoring system for clinical use is described. The method allows easy and reliable acute and chronic intracranial pressure registration in anesthetized as well as conscious rats. The disposable fiberoptic probes, originally designed for human use, can be re-used limitlessly. The fiberoptic method is compared with conventional monitoring procedures under different experimental conditions. The validity of intraparenchymal and epidural measurements is discussed. The importance of chronic intracranial pressure registration in conscious laboratory animals is stressed. PMID- 2308378 TI - The cone field: a spatial discrimination task for the automatic and simultaneous assessment of working and reference memory in rats. AB - A cone field apparatus was developed in which spatial working memory (WM) and reference memory (RM) can be assessed automatically and simultaneously. The cone field is a large open field with 16 cones in it. A configuration of four cones was baited with a food pellet. In the holeboard, the predecessor of the cone field, no clear criteria exist to distinguish between accidental and directed orientations toward the target (hole). In the cone field the visit to the target (cone) is unambiguously defined. We found that senescent rats were impaired on both the WM and the RM. The development of a fixed pattern of visiting the baited cones was effectively prevented by starting the rats randomly from four different positions. When only one start position was used, rats developed a fixed pattern of visiting the baited cones. This pattern was more pronounced in the young than in the senescent animals. In the last experiment we explored whether the task might be suited for the assessment of WM and RM performance in longitudinal studies. Rats performed like naive animals on both memory components when re acquisitions were separated by 4-month intervals without training. PMID- 2308379 TI - Evaluation of horseradish peroxidase as an intracellular stain in electrophysiological recording. AB - Iontophoresis of horseradish peroxidase into cells during intracellular electrophysiological recording to visualize the neurons recorded from is a powerful technique, but its success depends on a number of critical factors. The described agar injection technique is a simple method for the evaluation of several parameters at once, using procedures which closely resemble recording from, fixing, and processing to visualize the HRP in experimental tissue. PMID- 2308380 TI - Progressive incorporation of propidium iodide in cultured mouse neurons correlates with declining electrophysiological status: a fluorescence scale of membrane integrity. AB - We describe a visual assay of neuronal electrophysiologic status for use with cultured neurons, based on the exclusion of propidium iodide (PI) by intact cellular membranes. We use this fluorescent dye, which binds to nucleic acids, at concentrations suitable for long-term exposure to neurons without toxicity. We correlate the progressive loss of resting membrane potential and the progressive inability to generate stimulated action potentials by cultured mouse dorsal root ganglion neurons with increasing incorporation of PI. The scoring system used to gauge incorporation of PI is rapid and highly reproducible using a standard fluorescence microscope. Applications exist for studies of neuronal toxicity, survival, and electrophysiology in vitro. PMID- 2308381 TI - Automated determination of excitatory amino acid neurotoxicity in cortical culture. AB - We used a commercially available robotic laboratory workstation to quantitatively study excitotoxic neuronal injury in cell culture. A Beckman Instruments Biomek 1000 was programmed to perform both timed exposures to excitatory amino acid agonists, and kinetic assay of the resultant efflux of lactic dehydrogenase from damaged neurons, using 96-well culture plates. Examination of homocysteate neurotoxicity utilizing this automated method produced results similar to those obtained earlier using manual techniques. The method described here may facilitate the characterization of neurotoxic agonist or antagonist activity. PMID- 2308382 TI - Purification and polypeptide composition of corpora amylacea from aged human brain. AB - Corpora amylacea (CA) accumulation in the brain is a normal correlate of ageing. The presence of a small amount of protein in these polyglucosan bodies is a consistent finding, although the nature of this protein material remains unknown. Using sucrose gradient fractionation and density centrifugation on Percoll, a method was developed to obtain highly pure preparations of CA from human brain. The protein content of isolated CA was estimated to be approx. 4% of the total fraction by weight. SDS-PAGE analysis of CA fractions showed several polypeptide bands with molecular weights ranging from 24 to 133 kDa. Four of these bands with molecular weights of 133, 94, 42 and 24 kDa are more abundant. Thus, pure preparations of CA can be obtained that are suitable for protein analysis. PMID- 2308383 TI - Post-fixation horseradish peroxidase tracing in rat fetus and pups. AB - Horseradish peroxidase (HRP) has been shown to be applicable to fixed tissue in tracing projections in adult animals. This technique has several advantages in studying short projections in difficult attainable brain areas, especially with fetuses in utero. We have used this method to trace developing fibers (e.g., vestibulo-cerebellar connections) in rat fetuses and pups. It has been possible to make discrete and precise injections in any location. The quality of labeling by this method is distinctly related to the grade of fixation. Fixation grade determines how well HRP is anchored inside fibers and cell bodies. In optimally fixed preparations fibers and cell bodies are intensively stained with HRP up to over 3 mm from the center of an injection site. HRP is probably only taken up by damaged fibers so that the amount of fibers labeled is determined by the extent of the lesion caused by the injection pipette. PMID- 2308384 TI - A statistical test for demonstrating a presynaptic site of action for a modulator of synaptic amplitude. AB - A statistical technique for demonstrating a presynaptic site of action for a modulator of synaptic amplitude was developed and tested. It requires that multiple measurements of peak synaptic amplitude be made under control and test conditions. The ratio of the coefficients of variation (CV) obtained under test and control conditions is calculated. A method was developed for determining the confidence interval for the CV ratio (CVR) statistic based on the null hypothesis that the synaptic modulation is purely postsynaptic. If the measured CVR falls outside the confidence interval, this implies that the modulator of synaptic amplitude is, at least in part, acting at a presynaptic site. The effectiveness of the technique and its limitations were investigated using Monte Carlo simulations. It was found to be sensitive and reliable under a variety of realistic recording conditions. The test was effective even in the presence of simulated presynaptic rundown of the synaptic response. Conventional deconvolution analysis was also applied to the Monte Carlo simulations and was found to be an inadequate indicator of the site of synaptic modulation when the discrete amplitude components were not well resolved. The CVR technique was applied to excitatory postsynaptic currents (epsc) recorded between pairs of cultured hippocampal neurones in control and test media containing 1 mM Ca2+ and 2 mM Ca2+, respectively. Test conditions increased the average synaptic amplitude, and the statistical analysis indicated that this modulation was produced by an action at a presynaptic site. PMID- 2308385 TI - Association of Academic Health Centers (AHC) recommends actions to alleviate nursing shortages. AHC points to unresolved problems in nursing supply and education. PMID- 2308386 TI - A day in the life. "Will it hurt?". Interview by Linda DeMeb Hummel. PMID- 2308387 TI - Age-related changes of the ciliary muscle in comparison with changes induced by treatment with prostaglandin F2 alpha. An ultrastructural study in rhesus and cynomolgus monkeys. AB - The relationship between individual ciliary muscle cells and the surrounding connective tissue was studied in the eyes of three normal, young (3-4 years) cynomolgus monkeys (Macaca fascicularis), three aged (34-36 years) rhesus monkeys (Macaca mulatta) and seven young (3-7 years) cynomolgus monkeys topically treated with prostaglandin F2 alpha (PGF2 alpha) for 4-8 days. In normal eyes, collagen fibrils and microfibrils are in places in continuity with the muscle cells' basal lamina, which is connected to the cell membrane by fine fibrillous material. In old eyes, the basal lamina is markedly thickened, masking the connection of fibrils with the muscle cells' membrane. A distinctive finding in several muscle cells of old eyes are electronlucent clefts, 60-80 nm wide, between basal lamina and cell membrane, which are not transversed by fibrils or fibrillous material. The cell membrane of these muscle cells shows large folds filled with disarranged myofilaments. Additionally, these cells contain inclusion bodies consisting of concentrically arranged double membranes. Following treatment with PGF2 alpha, similar changes are seen in young animals, too. Here, the muscle cells have lost their connection to the extracellular fibrils due to a PGF2 alpha-induced lysis of extracellular material. Lack of attachment between basal lamina and altered muscle cells in aged eyes might indicate an involvement of the extracellular matrix in age-related changes of the individual ciliary muscle cells. PMID- 2308388 TI - Effects of donor age on osteogenic cells of rat bone marrow in vitro. AB - The effect of donor age on the production of bone-like tissue and expression of cellular alkaline phosphatase was examined in cultures of cells obtained from rat bone marrow. Stromal cells were obtained from the bone marrow of young (5-6 weeks) and old (18 months) rats and cultured in vitro. After 28 days in first subculture, the following were quantified: (1) the total number of mineralised nodules and the size distribution of nodules and (2) the density of osteoblasts and osteocytes associated with nodules in histological sections. The doubling times of the cultures and the numbers of cells in cultures which expressed alkaline phosphatase activity were determined in separate experiments. Cells from young cultures produced three times more bone-like nodules than old cultures, although no differences were seen in the size distribution of nodules, or on osteoblast and osteocyte density. Doubling times for both groups were similar. The numbers of alkaline phosphatase (AP) positive cells was reduced by half in old cultures. These data show that this model may be useful for the study of the mechanisms of ageing on osteogenesis, and demonstrate a reduced osteogenic capacity in old cultures. The results suggest that this effect may be due to a reduction in the generation of cells of osteoblast lineage during ageing. PMID- 2308389 TI - Effects of ethanol on microsomal drug metabolism in aging female rats. II. Inhibition. AB - The effect of aging on the inhibition by ethanol of drug metabolism activity was examined in liver microsomes of female Fischer 344 rats aged 4, 14 and 24 months. Inhibition of aniline hydroxylase activity in microsomes from 4-month-old females occurred at low concentrations of ethanol (0.1 mM) and was predominantly competitive. Aging was associated with a significant increase in apparent Km for aniline in the absence of ethanol (24 +/- 2, 20 +/- 2 and 32 +/- 1 microM in microsomes from 4-, 14- and 24-month-old rats, respectively) and a change from competitive to non-competitive inhibition by ethanol. Inhibition of benzphetamine N-demethylase activity occurred only at high concentrations of ethanol (100 mM) and was non-competitive in nature. There were no significant effects of aging on the kinetics of the reaction or the type of inhibition produced by ethanol. Microsomal ethanol oxidation rates were measured in liver microsomes of 4-, 15- and 25-month-old Fischer 344 rats of both sexes. Ethanol oxidation in males was greater than in females and was decreased significantly in old age. Ethanol oxidation in female rats was unaffected by aging. The results suggest that significant changes in drug/ethanol interactions can occur as a consequence of aging. PMID- 2308390 TI - Age related changes in the effect of electroconvulsive shock on the blood brain barrier permeability in rats. AB - Age-related changes in blood-brain barrier permeability to macromolecules were investigated during electrically induced seizures. Evans-blue was used as the barrier tracer. There was no change in the permeability of the blood brain barrier associated with aging in the rats. However, the extravasation of Evans blue albumin was most pronounced in the brain after ten repeated electroshocks in old rats. In the adult group that was given a single electroconvulsive shock, there was no coloration of the brain tissue, whereas the group given ten repeated electroconvulsive seizures showed slight staining of the thalamic nuclei, hypothalamus, and midbrain in 5 out of 13 rats. In 30-day-old rats, Evans-blue leakage was similar to that of adults, except that the frequency and intensity of blood-brain barrier breakdown was less after ten repeated electroshocks. In 15 day-old rats, the blood-brain barrier breakdown to Evans-blue albumin was the same after a single and ten electroshocks and the same in control and electroshocked rats. According to our results ten repeated electroshocks have a more pronounced effect on the old animals and have less effect on the young animals in comparison to adult ones. PMID- 2308391 TI - The ageing hypothalamo-neurohypophysial system. An analysis of the neurohypophysis in normal hydration, osmotic loading and rehydration. AB - Age-associated changes in the structure and function of the neurohypophysis may contribute to the decreased ability to conserve water in older animals. We investigated the neurohypophyses of 6 and 28-month-old male mice using radioimmunoassay and quantitative morphological techniques. The dry-weight and volume of the neurohypophysis increased significantly with age but the quantity of vasopressin in the gland remained constant. Oxytocin levels decreased with age. A quantitative morphological analysis was performed on the compartments of the neurohypophysis from male mice of 6 and 28 months of age which were either normally hydrated, osmotically loaded, or osmotically loaded and rehydrated. The absolute volumes of the axon endings, swellings, their constituent organelles and the axon terminals containing degenerating subcellular components were determined. The design of the analysis allowed us to examine both age-related changes and statistical interactions between the age of the animal and the behaviour of a variable during the osmotic loading/rehydration phase of the experiment. There was a significant age-related reduction in the volume of the neurohypophysis occupied by the endings and swellings. The diameters of the neurosecretory granules found in the endings were significantly smaller than those in the swellings in both age groups but the size difference was greater in the young animals. Dehydration and subsequent rehydration of old male mice leads to extensive re-modelling of the neurohypophysial compartments and subcellular organelles to the configuration found in the adult animal. PMID- 2308392 TI - Appearance of the terminal senescent cell population in human diploid fibroblasts analyzed by flow cytometry. AB - We studied changes in the distribution pattern of relative RNA content during the in vitro aging of TIG-3 cells by flow cytometry (FACS III). Propidium iodide (PI) does not stain total cellular RNA, but it intercalates specifically into double helical regions of both DNA and RNA. In applying this principle to RNA, we stained double-stranded RNA (dsRNA) in whole cells with PI after DNA digestion with DNase. The results showed that dsRNA distribution patterns were relatively constant at 7-75 population doublings (PD) but were significantly altered after 77 PD. The distribution patterns were similar as those for cell volume measured with a Coulter Counter. The total cellular dsRNA contents increased linearly at the senescent phase of their in vitro life span. In contrast, the mean dsRNA contents (50% dsRNA contents) rapidly increased to 77-79 PD, but decreased somewhat at 81-83 PD. Two-dimensional histograms of the dsRNA contents versus cell size were little altered from 25 PD to 75 PD. However, a population with relatively larger cell volume and weaker fluorescence intensity appeared and increased after 79 PD. This cell population group may be categorized as "terminal senescent cells" that no more divide in respect that the dsRNA content decreases in spite of the increase of total RNA content. PMID- 2308393 TI - Age-related changes of erythrocyte membrane in the senescence-accelerated mouse. AB - Age-related changes in erythrocytes in senescence-accelerated mice (SAM-P) and control mice with normal aging characteristics (SAM-R) were examined. A significant decrease in the number of erythrocytes and significant increases in MCV and ATP levels were observed with aging in SAM-P, while no significant changes were seen in SAM-R. Erythrocytes in aged SAM-P were less fragile than those in aged SAM-R. The contents of cholesterol and phospholipids in erythrocyte membranes increased significantly in aged SAM-P, but the molar ratio of cholesterol/phospholipid decreased. The plasma cholesterol level of SAM-P decreased with aging. Changes such as those observed in SAM-P were not seen in SAM-R during the period of observation. PMID- 2308394 TI - Phenotypic and functional properties of B lymphocytes from aged mice. AB - Phenotypic and functional properties of B lymphocytes from individual young and old mice of different inbred strains were studied. B lymphocyte subpopulations defined by the ratios of the densities of cell surface IgM and IgD were found to be altered with age. However, such alterations in B cell subsets were found only in 30-40% of the old mice. B cell mitogenic responses to anti-mu and anti-Lyb2 antibodies were decreased in a majority of DBA/2 mice. Proliferative responses to LPS and anti-mu were reduced only in a minority of CBA/Ca mice but there was a very good correlation in the responsiveness of the old mice to LPS and anti-mu. The anomalous properties of the individual old mice of these inbred strains may be due to a heterogeneity in the effects of aging or due to environmental influences. PMID- 2308395 TI - Age differences on ileal glucose absorption in rats. AB - Ileal absorption of D-glucose was studied in fasted 21-day-old and 18-month-old rats for a 5-min period using a perfusion technique in vivo. D-Glucose initial concentrations were: 2.5, 5, 10, 20 and 40 mmol/l. Phloridzin (0.5 mmol/l) was used as inhibitor of the active transport mechanism, inducing a 65 and 70% inhibition in the ileum of the young and old rats, respectively, at 40 mmol/l initial sugar concentration. Saturation was at 10 mmol/l in the two groups studied. A reduction in the rate of total sugar absorption, active transport and diffusion coefficient was observed with aging. PMID- 2308396 TI - Respiratory activity of isolated rat liver mitochondria following in vitro exposure to oxygen species: a threshold study. AB - Respiratory activity of isolated rat liver mitochondria was assayed following in vitro exposure to oxygen radicals. Our results show that mitochondrial respiration is more sensitive to O2.(-) than to H2O2. However, ferrous ions drastically enhance the toxicity of the enzymatic system generating H2O2 because of the production of the hydroxyl radicals. A protection against those oxygen species could be given by SOD in the xanthine/xanthine oxidase system and by catalase with the glucose/glucose oxidase system. The most damaging system was the combination of Fe2+ with H2O2. In this case, OH. is formed in a Fenton-like reaction. The fact that the OH. is the most damaging molecule accounts for the finding that catalase and desferrioxamine were efficient protectors in this system. Threshold levels of O2.(-) and H2O2 able to inhibit the mitochondrial respiration have been estimated. It is concluded that under normal respiration such thresholds are not reached in vivo and that the impairment of the mitochondrial respiratory activity does not seem to originate only from the natural free radical production in those organelles. However, if the production of free radicals is such to exceed the defense capability, like under oxidative stress, then the critical threshold can be surpassed and the respiration impaired leading to irreversible damages. PMID- 2308397 TI - Age-related changes in adrenaline content of rat splanchnic blood vessels. AB - The influence of ageing on the adrenaline content of the superior mesenteric artery and vein, renal artery and vein and portal vein was studied in 3-month- (young), 12-month- (adult) and 24-month-old (old) male Wistar rats using radioenzymatic assay for the measurement of catecholamine levels. Adrenaline concentrations were unchanged in the vascular wall of the blood vessels examined in adult rats, but were significantly decreased in the vascular wall of the superior mesenteric, renal and portal veins of old rats. In contrast, no age dependent changes of adrenaline levels were found in the vascular wall of the superior mesenteric or renal arteries. The possibility that the loss of adrenaline concentrations in the venous vascular wall may be in some way related to the cardiovascular impairment occurring with age is discussed. PMID- 2308399 TI - [A model is investigated at the Karolinska Institute: increased interest in keeping records of research material]. PMID- 2308398 TI - Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. AB - Glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase are the most important enzymes of the cell antioxidant defense system. However, these molecules are themselves susceptible to oxidation. The aim of this work was to estimate to what extent this system could be inactivated by its own substrates. We tested the effect of hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide and hydroxyl and superoxide radicals on GPX, SOD and catalase. For GPX, a 50% inactivation was observed at 10(-1) M (30 min, 37 degrees C) for hydrogen peroxide, 3 x 10(-4) M (15 min, 37 degrees C) for cumene hydroperoxide and 5 x 10(-5) M (11 min, 37 degrees C) for t-butyl hydroperoxide. Unlike the hydroxyl radicals, superoxide anions did not inactivate this enzyme. Catalase was inactivated by hydroxyl radicals and by superoxide anions but organic peroxides had no effect. SOD was inactivated by 50% by hydrogen peroxide at 4 x 10(-4) M (20 min, 37 degrees C), but organic peroxides and hydroxyl radicals were ineffective on this enzyme. Since the three enzymes of the antioxidant system are susceptible to at least one of the oxidative reactive molecules, in the case of high oxidative stresses such an inhibition could take place, leading to an irreversible autocatalytical process in which the production rate of the oxidants will continuously increase, leading to cell death. PMID- 2308400 TI - [Ovarian cancer]. PMID- 2308401 TI - [Beware of bubble-pools]. PMID- 2308402 TI - [Vaginal discharge--hazardous self-care using over-the-counter drugs]. PMID- 2308403 TI - [Better to generalize than to include all chlamydia infections in venereology]. PMID- 2308404 TI - [Don't underestimate the information given by midwives about contraception]. PMID- 2308405 TI - [An analysis of the debate on the concept of death as an instrument to unravel controversy]. PMID- 2308406 TI - [Testicular torsion must be dealt with immediately]. PMID- 2308407 TI - [Treatment of bacterial vaginosis--an acid gel as an alternative to antibiotic treatment]. PMID- 2308408 TI - [Analyses of alcohol performed at hospitals are not quite reliable. External quality control should be performed at least once a year]. PMID- 2308409 TI - [The National Board of Health and Welfare prohibits Ecomer. Shark liver oil is suspected of adverse effects]. PMID- 2308410 TI - [Risk of myocardial infarction is increased among transportation and industry workers]. PMID- 2308411 TI - [Increased risks of cancer can be explained by the type of occupation and life style]. PMID- 2308412 TI - [Studies based on registries can give a wrong picture. Morbidity in physically light occupations will increase]. PMID- 2308413 TI - [Paroxysmal supraventricular tachycardia--always benign?]. PMID- 2308415 TI - [Child abuse and custody disputes: when should the caregiver report the case to police and social services, and when is there an obligation to do so?]. PMID- 2308414 TI - [Spontaneous coronary artery dissection treated by bypass surgery]. PMID- 2308416 TI - [The CHAD project: society-oriented medical education in India]. PMID- 2308417 TI - [Venous thromboembolism--practice and consensus. A great number of thromboses do not need surgery]. PMID- 2308418 TI - [Uncertainties about the climacteric syndrome]. PMID- 2308419 TI - [Psychotherapy of psychoses--research according to valid ethical standards?]. PMID- 2308420 TI - [Wrong conclusions based on blood pressure measured intra-arterially and using a standard cuff]. PMID- 2308422 TI - [Intermittent spinal claudication--renaissance of an old syndrome]. PMID- 2308421 TI - [Reactions of men after sterilization. All satisfied with the consultation at the Maternal Health Center]. PMID- 2308423 TI - [A visit to the Fetal Treatment Program in San Francisco: the only place where open fetal surgery is done]. PMID- 2308424 TI - [There is great interest in research on fetal medicine and fetal surgery]. PMID- 2308425 TI - [Heart Beat Wales: a wide-spread cardiovascular project]. PMID- 2308426 TI - [Understanding the problem concerning the occupational environment of physicians during their internship]. PMID- 2308427 TI - [Not much news for Sweden in new international hypertension guidelines]. PMID- 2308428 TI - [Even adoptive parents should be screened for HIV!]. PMID- 2308429 TI - [What role does the metabolic effect have after changing to a lacto-vegetarian diet?]. PMID- 2308430 TI - [Difficulties in replacing mercury as a preservative in bacterial vaccines]. PMID- 2308431 TI - [Para-malignant phenomena in liver cancer]. PMID- 2308432 TI - [Positive results of a care program for patients with hip fractures in New York]. PMID- 2308433 TI - [Shortening of life during adequate care--legislate to prevent uncertainties!]. PMID- 2308434 TI - [Shortening of life during adequate care is not a question suitable for legislation]. PMID- 2308435 TI - [An education model in Linkoping: professional patients teach students the gynecologic examination technic]. PMID- 2308436 TI - [The gynecologic examination technic: students are more competent to do palpation after teaching by professional patients]. PMID- 2308437 TI - [Orphan drugs--competing for a better name in Sweden]. PMID- 2308438 TI - [Endoscopic microsurgical dissection of the esophagus: a contribution to the reduction of pulmonary complications following esophageal resection? A comparative animal experiment study]. AB - A new endoscopic microsurgical technique for dissection of the esophagus has been developed and tried out in animals. With this technique the esophagus is dissected and removed via a cervical approach by means of a new operating endoscope. In a randomized animal study we compared endoscopic versus blunt dissection and versus abdominothoracic resection. During endoscopic dissection we saw significantly lower bleeding and no laceration of the pleural cavity or damage to the recurrent laryngeal or to the vagus nerve. Significant changes of hemodynamics or gas exchange were observed in the blunt dissection group: increase of heart frequency, decrease of arterial pressure and decrease of paO2. In contrast these parameters did not change in the endoscopic group. PMID- 2308440 TI - [Limited esophageal surgery?]. PMID- 2308439 TI - [Topography of the upper biceps tendon segment]. AB - 26 shoulders are studied by polariscopic and histologic examination. It can be confirmed that the origin of the long biceps tendon is not only at the supraglenoid tubercle, but also y-shaped in the glenoid labrum. This finding can be explained by phylogenetic means. Further details are found during the course of the tendon through the bicipital groove. A mesotenonium is seen regularly. This is fixed either to the roof or the ground of the sulcus by a band of connective tissue. It is shown also, that the roof of the groove is not a ligament (ligamentum transversum humeri) but consists of collagen fibers continuing from the subscapularis and capsular attachment at the lesser tubercle. PMID- 2308441 TI - Fibromatosis--a rare retroperitoneal tumour. AB - A case of retroperitoneal fibromatosis in a 28-year-old white male is presented. The soft tissue tumor, with a weight of 8000 g, was resected by laparotomy. Because of adhesions to the ascending colon and the right ureter, a hemicolectomy and partial resection of the right ureter had to be performed additionally. Intraabdominal fibromatoses are very infrequent tumorous lesions of the connective tissue, occurring retroperitoneally only in isolated cases. Their etiology is presumed to be a hereditary or gene-associated defect in the regulation of connective tissue growth. In addition, trauma and hormonal influences often appear as inductive cofactors. PMID- 2308442 TI - [Complex trauma of the perineum, especially the anorectal continence organ. Experiences and results in 27 patients 1956-1988]. AB - This report is based upon 27 patients with severe perineal injuries treated in a 30-year-period. Four groups of injuries could be identified. Severity of the trauma, correct diagnosis of concomitant injuries, right usage of antibiotics and protection of the perineal wound by a temporary colostomy represented key factors for a favorable outcome. There is evidence from our data that primary repair should be carried out immediately for tears of the anorectal sphincter. Even if the organ of continence as a whole is separated from the pelvic floor, good functional results can thus be achieved. Extensive scar formation must be prevented as secondary sphincter reconstruction (gracilis muscle transposition) was never successful in our patients. All these cases required a permanent colostomy. Concomitant tears of the membranous urethra frequently caused urethral stenoses and irreversible impotence. Mortality rates were low in patients with severe perineal injuries. PMID- 2308443 TI - Size variations in the lateral intercellular spaces of the endolymphatic sac induced by dietary factors. AB - Since much evidence suggests that the endolymphatic sac is responsible for endolymph resorption, and that the endolymphatic sac lateral intercellular spaces which are lined by the energy-dependent transport complex NA+,K(+)-ATPase are important in this process, we sought to evaluate the effects of dietary salt and a food extract that inhibits the activity of Na+,K(+)-ATPase on lateral intercellular space size. Animals fed this food factor and a high-sodium diet had significantly smaller endolymphatic sac lateral intercellular spaces than those animals fed only a high-sodium diet (analysis of variance with Scheffe's multiple comparison test, P less than 0.001). Animals fed a high-sodium diet had significantly larger endolymphatic sac lateral intercellular spaces than those animals fed a control diet only (analysis of variance with Scheffe's multiple comparison test, P less than 0.001). Results of this study suggest that dietary sodium affects endolymphatic sac fluid dynamics and that other food factors may regulate sodium metabolism, and therefore endolymphatic sac function. PMID- 2308444 TI - Speech recognition ability as a function of duration of deafness in multichannel cochlear implant patients. AB - Surgical implantation of a multichannel cochlear prosthesis has become a widespread treatment for profound hearing loss. The relationship between duration of hearing loss and speech recognition ability was examined in 20 postlinguistically deafened adults using the Nucleus 22-Channel Cochlear Prosthesis. Data analysis indicated statistically significant negative correlations between duration of profound hearing loss and postoperative performance on the Central Institute for the Deaf Everyday Sentence Test and the Northwestern University Monosyllabic Word Test (NU-6). Age at implantation and age at onset of profound hearing loss were not found to be significantly correlated with performance on the two measures. These findings are discussed in terms of patient counseling and prediction of potential benefit to the patient. PMID- 2308445 TI - Autoimmune hypothesis of acquired subglottic stenosis in premature infants. AB - Acquired subglottic stenosis is a devastating additional burden for nearly 4% of premature infants receiving neonatal intensive care. The duration of endotracheal intubation is considered the most important etiologic factor. Surprisingly, most premature infants do not acquire subglottic stenosis. Infants with similar clinical characteristics and care have varying laryngeal outcomes. We hypothesized an autoimmune mechanism to type-II collagen to explain the varying laryngeal outcomes of these infants. A retrospective study of premature infants of comparable birth weight, gestational age, and duration of endotracheal intubation was conducted. The eight control children, who did not manifest symptoms of airway obstruction, had longer durations of intubation than did the infants who developed subglottic stenosis. Three of five affected infants had serum antibodies to type-II collagen, in contrast to none of the control infants (P = .035). This finding warrants additional study, and might lead to new diagnostic and therapeutic measures for these patients. PMID- 2308446 TI - Head and neck sequelae of cardiac transplantation. AB - Cardiac transplantation has become the treatment of choice for end-stage cardiomyopathies. In 1987, nearly 2000 cardiac transplants were performed in the United States. Otolaryngologists will be asked with increasing frequency to evaluate and treat these patients. The otolaryngology service at Loyola University Medical Center has been involved in the follow-up and treatment of head and neck complications in 100 transplant patients. Sixty percent of these patients manifest head and neck sequelae. The results of this review are presented. The otolaryngologist should be aware of the special features of this patient population that require modification of the treatment approach, such as 1. the need to avoid the drugs erythromycin, trimethoprim/sulfamethoxazole, and ketoconazole, 2. the need to preserve the right internal jugular vein, and 3. the high risk of silent myocardial infarction. A discussion of these treatment modifications is provided. All patients should be treated in close communication with the medical transplant treatment team. PMID- 2308447 TI - Improvement in speech perception and production abilities in children using a multichannel cochlear implant. AB - Nine children received the Nucleus multichannel cochlear prosthesis. The preoperative evaluation consisted of assessments of auditory function, speech recognition, linguistic skills, and speech production. There were no surgical complications, and recovery in all patients was uneventful. The device was programmed 4 to 5 weeks following surgery, and all children were conditioned to the task. Postoperative training began immediately following device stimulation and is ongoing. Auditory skills and speech production scales were devised to monitor each child's progress. All children have shown varying degrees of improvement in auditory skills and speech production using the implant alone. PMID- 2308448 TI - Composite autograft for tympanoplasty and tympanomastoid surgery. AB - In 1982, 40 composite cartilage perichondrial autografts performed to prevent recurrent cholesteatoma secondary to canal wall defects were reviewed. A follow up of those cases, plus 62 new cases, as well as the composite autografts for severe tympanic membrane retractions (55 cases) and selected tympanoplasties (22 cases) is presented. No recurrent cholesteatomas or retraction pockets developed at the graft sites, with one graft failure in the latter group. PMID- 2308449 TI - Upper airway measurements predict response to uvulopalatopharyngoplasty in obstructive sleep apnea. AB - Although uvulopalatopharyngoplasty relieves obstructive sleep apnea in the majority of patients, the factors that determine a successful response are not well defined. To determine whether preoperative awake upper airway measurements predict the response to uvulopalatopharyngoplasty, presurgical lateral cephalometric radiographs were evaluated on 60 consecutive patients with symptomatic obstructive sleep apnea. Patients underwent overnight polysomnograms before uvulopalatopharyngoplasty and 3 months afterwards. Forty-eight (80%) patients had a good response as defined by a postoperative apnea index of less than or equal to 4 apneas/hour or a reduction in apnea index of greater than or equal to 60%. Responders had a significantly narrower inferior airway space (P less than .0005) and a smaller ratio of inferior airway space to tongue length (P less than .001). Improvement in apnea severity following uvulopalatopharyngoplasty was related to the degree of airway narrowing (r = 0.36; P less than .01). This study shows that upper airway measurements help predict response to uvulopalatopharyngoplasty in patients with obstructive sleep apnea. Patients with a narrow airway, particularly relative to tongue size, have good responses to uvulopalatopharyngoplasty. PMID- 2308450 TI - The use of injectable collagen to correct velopharyngeal insufficiency. AB - The use of Gax collagen is proposed for correcting velopharyngeal insufficiency with posterior pharyngeal wall augmentation. The indications for this procedure are velopharyngeal insufficiency that remains after surgery and treatment by a speech pathologist. The procedure is also valuable after velum paralysis. Collagen (2.5-5cc) is injected through a device designed for vocal-fold and laryngeal rehabilitation. Several injection points are necessary to raise a good Passavant's ridge. The muscular activity of the posterior pharyngeal wall models the collagen pad for the first 3 weeks; afterwards, the collagen shape remains unchanged due to its integration in the host tissues. At this time, five patients have been injected with Gax collagen and have improved. The oldest case dates from 28 months ago; the most recent dates from 8 months ago. There were no adverse reactions, and the results remain stable at the present time. PMID- 2308451 TI - Production rate and composition of cerumen: influence of sex and season. AB - The production rate and composition of cerumen have been studied in 11 participants (5 men and 6 women), 25 to 42 years old. The cerumen was obtained in January, May, July, and November to investigate the possible influence of the season. Only the triglyceride content decreased from November to July. Sex was not a factor, which supported the hypothesis that sex hormones play a minor role in the production rate of the lipid component of cerumen. PMID- 2308452 TI - Chronic pediatric stridor: etiology and outcome. AB - Stridor in children is usually acute. This paper represents a chart review and telephone survey of 60 patients with chronic pediatric stridor. The most common etiology was laryngomalacia, which required airway intervention in 22% of the patients. The symptoms persisted beyond 18 months of age in 17% of the patients. Twelve percent of the patients had multiple lesions; 65% of the second lesions were below the vocal cords. It appears that the presence of cyanosis should increase physician suspicion of multiple lesions. There was not a higher risk of recurrent upper respiratory infections with any of the diagnoses. PMID- 2308453 TI - Clinical application of an implantable bone conduction hearing device. AB - For some patients, the transcutaneous bone-conduction implant offers a viable alternative to conventional amplification. However, this option should be employed only after considering the relative advantages and disadvantages of conventional medical management and, when feasible, the fitting of air-conduction amplification. The cases presented here illustrate some important factors to consider in the selection and fitting of bone-implant candidates. PMID- 2308454 TI - Rhinosurgical experience with the transseptal-transsphenoidal hypophysectomy: technique and long-term results. AB - Many modifications of extracranial transsphenoidal hypophysectomy exist, but knowledge of the rhinological implications of these procedures is rare. At our institution the transseptal approach is performed as a joint rhinosurgical and neurosurgical procedure. Three hundred nineteen patients were operated on from 1979 to 1984, 113 of whom had a rhinological follow-up for 5 years. Most of the complications were asymptomatic. Thirteen percent of the patients had septal perforations, 3.5% epistaxis, and 36% complained of mild dryness of the nose. An improvement in breathing was noted in 24% of the patients. There was no difference in rhinological complaints between patients who underwent the sublabial approach and those operated via a transnasal approach. Twenty percent of the patients operated on with the sublabial approach had additional temporary complaints in the upper lip; therefore, the transnasal-transseptal approach is currently our procedure of choice. PMID- 2308455 TI - Laryngeal brainstem evoked response: a developmental study. AB - A developmentally receding laryngeal chemoreflex (LCR) has been described in infant animals of several species characterized by vocal cord adduction in response to laryngeal stimulation as well as a potentially fatal cardio respiratory response. Age-related differences in the brainstem respiratory centers may account for differences in the LCR and play a role in such disorders as Sudden Infant Death Syndrome (SIDS) and infant apnea. Study of the LCR at the brainstem level could provide insights into normal maturation of respiratory centers and eventually the pathophysiology of these disorders. The present study evaluated the laryngeal brainstem response (LBR) evoked by electrical stimulation of the superior laryngeal nerve in kittens using a far-field technique similar to auditory brainstem response testing. Recordings were obtained via posterior pharyngeal and posterior cervical recording sites and compared to results previously obtained in our laboratory for adult cats. The LBR in kittens demonstrated differences in threshold, latencies, and morphology which suggests that postnatal maturation of laryngeal function at the brainstem level does occur. PMID- 2308456 TI - Pharyngeal myotomy for voice restoration: a midline approach. PMID- 2308457 TI - Clinical applications of tissue expansion in head and neck surgery. AB - Tissue expansion offers a new frontier in head and neck reconstruction in that it provides the capability of creating additional new skin for restoration of defects with skin of identical color, thickness, and appendages. The applicability of tissue expansion is only beginning to be appreciated as it is used in various aspects of head and neck surgery. Currently, the technique is most frequently used in scalp surgery for correction of male pattern baldness. Other uses of tissue expansion are in cranial facial surgery and expansion of distant, regional, or microsurgical flaps. Perhaps its greatest value from a reconstructive perspective, however, is in providing new skin for reconstruction of various facial defects through the use of primary wound closure or a multitude of local flaps. PMID- 2308458 TI - Management of congenital preauricular pit and sinus tract in children. PMID- 2308459 TI - Laser medicine: great possibilities, guarded prognosis. PMID- 2308460 TI - Nd:YAG laser-induced interstitial hyperthermia using a long frosted contact probe. AB - The heating potential of a closed loop interstitial hyperthermia system employing 1,064 nm laser light in conjunction with a long frosted contact probe was investigated in hind limb muscle of anesthetized dogs. The laser system was an Nd:YAG surgical laser modified with a single channel thermometry unit, a computer, a printer, and a computer-controlled laser exposure shutter. The long frosted laser probe was implanted into the muscle, and 3.12-5.00 Watts of laser power was delivered interstitially. Temperature distribution was measured in three dimensions around the frosted probe. The temperature distributions generated by this technique were satisfactory for producing desired hyperthermia temperatures in an approximately 3.5 cm3 cylindrical tissue volume. A multiple laser delivery system is needed to induce interstitial hyperthermia in large tumors. A significant potential for the long frosted contact probe may be its use in combining interstitial hyperthermia and interstitial photodynamic therapy. Using this technique, both modalities may be delivered while employing the same treatment setup. PMID- 2308461 TI - Thermally induced optical property changes in myocardium at 1.06 microns. AB - Light in the visible and near-infrared region is diffusely scattered in tissues by macromolecules. It was therefore hypothesized that tissue coagulation caused by high-power continuous wave laser irradiation might significantly alter tissue optical properties, resulting in a redistribution of laser energy during the laser ablation process. Infrared transmittance studies confirmed the hypothesis by demonstrating an irreversible decrease in light transmittance (45%) during heating of a 0.75 mm thick slice of tissue. Absorption and scattering coefficients were then determined from transmittance and reflectance measurements on thin slices of raw and coagulated myocardium irradiated with a Nd:YAG laser (1.06 microns). The scattering coefficient was found to increase fourfold (0.427 mm-1----1.74 mm-1) during tissue coagulation, while the absorption coefficient remained relatively unchanged (0.044 mm-1----0.051 mm-1). Calculations indicate that the coagulation-induced changes in tissue optical properties substantially increase surface back-scattering and reduce tissue penetration. PMID- 2308462 TI - Does low-intensity helium-neon laser irradiation alter sensory nerve active potentials or distal latencies? AB - The effect of 1 mW helium neon continuous-wave (0.633 microns) laser irradiation on superficial radical sensory and median sensory nerve function was examined in a double-blind, controlled study involving 40 volunteers. No differences in action potential amplitudes, distal latencies, or forearm skin temperatures were found between the treated and control groups either at the time of irradiation or at subsequent evaluations 15 and 30 minutes later. As a result, we are unable to confirm reports that low-energy lasers of this power and wavelength alter nerve function. PMID- 2308463 TI - Helium-neon laser irradiation inhibits the growth of kidney epithelial cells in culture. AB - We have investigated the in vitro action of helium-neon (He-Ne) laser light on the cell cycle and the growth of rat kidney epithelial cell cultures. Dose response studies showed that repeated He-Ne irradiation (dose rate 40 mW/cm2) once a day in a dose range between 11.9 and 142 J/cm2 significantly inhibited cell growth, while daily irradiation with 4.7 J/cm2 had no effect. Microscopic examination of nuclear spreads revealed an increased number of cells in mitosis after a single irradiation with 142 J/cm2. These results support previous observations suggesting that laser light of low thermal energy interferes with cell cycling and may inhibit cell growth when irradiation is performed at doses of 11.9 J/cm2 or more. PMID- 2308464 TI - Ablation of recurrent and metastatic intraabdominal tumor with the CO2 laser. AB - A retrospective study was carried out to determine the usefulness of the CO2 laser in the management of patients with recurrent and metastatic intraabdominal tumors. Twenty-six intraabdominal procedures utilizing the laser were carried out on 24 patients at The Ohio State University between 1984 and 1988. This included 11 patients with recurrent adenocarcinoma of colonic origin, 3 patients with malignant carcinoid tumors, 3 patients with ovarian carcinomas, and one patient each with metastatic pheochromocytoma, appendix, breast, stomach, and lung carcinoma. In addition, there was one patient with pseudomyxoma peritoneii and one patient with both colonic and ovarian carcinoma. Tumors were located in the retroperitoneum (3), pelvis (2), liver (11), bowel serosa (5), diaphragm (4), mesentery (3), and peritoneal implants (3). The laser was used as an adjunct to standard surgical techniques and in most instances was combined with other operative procedures. Its use was greatest in cases where en bloc resection was impossible, as with hepatic lesions located near the hepatic veins or vena cava. Additional benefit was derived in cases where cytoreductive or debulking surgery was useful as in ovarian carcinoma and metastatic neuroendocrine tumors. All four patients with neuroendocrine tumors are still alive 3, 7, 12, and 56 months after surgery. In addition, symptom relief was apparent in all after surgery. All patients with ovarian carcinoma are also alive 9-29 months after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308465 TI - Irradiation of pigmented melanoma cells with high intensity pulsed radiation generates acoustic waves and kills cells. AB - Photokilling of pigmented mouse melanoma cells (B-16) was investigated using pulsed high intensity visible radiation. Melanin acts as an endogenous chromophore, and 694 nm radiation with 40 nsec pulse duration and 0.5-3 X 10(7)w/cm2 intensity causes cell death. Irradiation of non-pigmented human melanoma cells (U1) or human squamous carcinoma cells (FaDu) under similar conditions did not kill the cells. Also, irradiation of B-16 cells with 300 microsec laser pulses (10(3)W/cm2) or with continuous wave (CW) radiation (10( 3)W/cm2) did not kill the cells. These data indicate that pigmented cell killing is due to absorption of radiation by melanin and that the pulsewidth and intensity of radiation play important roles in cell killing. The generation of acoustic waves due to absorption of the pulsed radiation by pigmented cells and by isolated melanosomes was demonstrated at 532 and 625 nm and 8.5 nsec pulse duration (10(7)-10(8) W/cm2); the amplitudes of the acoustic signals were approximately 2.5-3.0-fold higher at 532 nm compared with 625 nm, and they increased with increasing fluence. In contrast, irradiation of U1 or FaDu cells with comparable fluences and intensities did not generate acoustic waves. A possible correlation between the generation of photoacoustic waves and pigment cell death is proposed. Since the thermal relaxation time of melanosomes is 0.5 1.0 microsec, the mechanism proposed is that thermal confinement of high intensity, short-pulse visible radiation generates acoustic waves by thermal expansion, leading to mechanical damage to the cells. PMID- 2308466 TI - Assessment of laser-induced release of drugs from liposomes: an in vitro study. AB - We evaluated the characteristics of laser-induced release of an antimetabolite (cytosine arabinoside) from temperature-sensitive liposomes. Previous work had shown that a laser would induce breakdown of liposomes when a dye was encapsulated within the liposomes. The present investigation was performed to determine if release could be induced from liposomes that did not contain dye. In vitro, dynamic studies of the release of the drug from liposomes diluted in blood (flowing in a capillary tube at 40 microns/min) were conducted using an argon dye laser operating either in the blue-green mode (488/514 nm) or in the dye mode (577 nm). A radio-labeled marker was used to monitor the drug release. The results showed that the drug could indeed be released from liposomes that did not contain dye, at energy levels that are not likely to be harmful to the tissue. At identical power levels, the release of the drug was greater at 577 nm than at 488/514 nm, probably owing to the greater light absorbance of hemoglobin at the longer wavelength. The results indicate the potential for the site-specific release of a variety of molecules in the ocular vasculature. PMID- 2308467 TI - Endometrial laser ablation in rabbits: a comparative study of three laser types. AB - Endometrial laser ablation is one of the alternatives to hysterectomy in cases of intractable uterine bleeding. It is currently performed using the Nd:YAG laser at 1.06 microns. The aim of this study was to compare the tissue effect of three types of laser irradiation (Nd:YAG laser at 1.06 and 1.32 microns and holmium laser at 2.12 microns) on the rabbit endometrium. Crater formation, coagulation necrosis, and muscle necrosis were evaluated at the time of ablation, as well as at 1 week and 4 weeks postablation. The results were assessed by determining the depth and width of the affected portion in the uterine wall (lumen to serosa). It was shown that Nd:YAG laser at 1.32 microns caused more generalized and extended effects as compared with the other laser types examined. Endometrial regeneration was faster after ablation by the Nd:YAG laser at 1.06 microns and the holmium laser than by the Nd:YAG laser at 1.32 microns. The widest range of "ablation energy" (defined as that causing ablation without muscle damage) was achieved by applying the holmium laser. Further evaluation of the holmium laser for this indication is recommended. PMID- 2308468 TI - Thermal damage produced by high-irradiance continuous wave CO2 laser cutting of tissue. AB - Thermal damage produced by continuous wave (cw) CO2 laser ablation of tissue in vitro was measured for irradiances ranging from 360 W/cm2 to 740 kW/cm2 in order to investigate the extent to which ablative cooling can limit tissue damage. Damage zones thinner than 100 microns were readily produced using single pulses to cut guinea pig skin as well as bovine cornea, aorta, and myocardium. Multiple pulses can lead to increased damage. However, a systematic decrease in damage with irradiance, predicted theoretically by an evaporation model of ablation, was not observed. The damage-zone thickness was approximately constant around the periphery of the cut, consistent with the existence of a liquid layer which stores heat and leads to tissue damage, and with a model of damage and ablation recently proposed by Zweig et al. PMID- 2308469 TI - Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer. AB - 4-Hydroxytetrahydroisoquinoline (4OH-TIQ) was detected as a metabolite of a possible parkinsonism-inducing substance, tetrahydroisoquinoline (TIQ), in rat liver microsomes and rat urine. Urinary excretion of 4OH-TIQ was significantly reduced in female DA rat, an animal model of a poor debrisoquine metabolizer. The female DA rat also showed significantly higher brain accumulation of TIQ. These results suggest that the metabolic detoxication process is depressed and TIQ accumulation in the brain is enhanced in a poor debrisoquine metabolizer, which may be one possible explanation for poor debrisoquine metabolizers being susceptible to Parkinson's disease. PMID- 2308470 TI - Effect of cytochalasin B on the uptake of ascorbic acid and glucose by 3T3 fibroblasts: mechanism of impaired ascorbate transport in diabetes. AB - Hyperglycemia and/or hypoinsulinemia have been found to inhibit L-ascorbic acid cellular transport. The resultant decrease in intracellular ascorbic acid may de inhibit aryl sulfatase B and increase degradation of sulfated glycosaminoglycans (sGAG). This could lead to a degeneration of the extracellular matrix and result in increased intimal permeability, the initiating event in atherosclerosis. The present studies show that the glucose transport inhibitor cytochalasin B blocked the uptake of 3H-2-deoxy-D-glucose (2.5 mg%) by mouse 3T3 fibroblasts. Cytochalasin B also blocked the uptake of 14C-L-ascorbic acid (1.25 mg%). The results of these studies further support the hypothesis that glucose and ascorbate share a common transport system. This may have important implications concerning the vascular pathology associated with diabetes mellitus. PMID- 2308471 TI - Growth hormone and prolactin response to methylphenidate in children with attention deficit disorder. AB - Utilizing a double-blind, drug-placebo design, we examined growth hormone (GH) and prolactin (Pro) response to oral administration of methylphenidate (MPH) in 14 boys (ages 7.0-12.4 years) with Attention Deficit Disorder (ADD). Four conditions representing three different MPH doses (0.3 mg/kg O.D., 0.3 mg/kg B.I.D., 0.6 mg/kg O.D.) and Placebo were compared in each subject, each condition lasting for a period of 3 weeks. GH and Pro response were measured both as maximum peak GH (DGH) or nadir of Pro (DPro) as well as area under the curve for the first four hours after MPH administration (AUCGH, AUCPro). Behavioral measures included parent ratings on the Yale Children's Inventory and teacher ratings on the Yale and Conners Behavior Rating Scales and Kagan's Matching Familiar Figures Test (MFFT). Prolactin response as measured by AUCPro was significantly increased after MPH compared to placebo (t = 2.04, p less than 0.05, placebo vs all doses MPH). This difference observed for AUCPro between placebo and MPH was evident as well when we considered the number of times AUCPro declined after MPH as compared to placebo (p = .018, Fisher's exact test). Within subjects analysis of covariance demonstrated significant correlations between the improvement in reaction time on the MFFT and 1) GH response (AUCGH, r = .58, p less than .001) and 2) prolactin response (AUCPro, r = .40, p less than .05) and between improvement in attention as measured on the Yale BRS and GH response (AUCGH, r = .57, p less than .05). Our findings suggest that measures other than GH and prolactin may be more desirable measures of brain catecholaminergic functioning. PMID- 2308472 TI - Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: a structure-activity study. AB - Structure-activity relationships for cocaine and analog binding at the dopamine, norepinephrine and serotonin transporters were determined. Cocaine inhibition of ligand binding to each of these sites has a stereospecific requirement for the levorotatory isomer. Binding potencies of cocaine derivatives involving N substitution, C2 and C3 substituent modifications, however, revealed differences in structure-activity relationships for cocaine binding at the transporters. Removal of the N-methyl groups produced little change in binding potency at the dopamine transporter site but produced increases in binding potency at norepinephrine and serotonin transporter sites. Changes in structure at the C2 substituent produced changes in binding potency at the dopamine transporter which were generally similar in direction, but not necessarily in magnitude at the norepinephrine and serotonin transporters. Modifications to the C3 substituent, especially substitution of a hydroxyl moiety, produce changes in affinity at norepinephrine and serotonin transporters which are much larger than those observed at dopamine transporters. In general, our results indicate that unique structural requirements exist for each transporter site, but that cocaine binding at norepinephrine and dopamine transporters can be described by more similar structure-activity relationships than those found for the serotonin transporter. Requirements for cocaine binding to the dopamine transporter, which we have previously shown to be associated with the reinforcing effects of cocaine, include levorotatory stereospecificity, the benzene ring at C3, at least some portions of the tropane ring, and the presence of the C2 methyl ester group in the beta conformation. PMID- 2308473 TI - Determination of circulating blood volume by measurement of indocyanine green dye in hemolysate: a preliminary study. AB - In 8 emergency care patients blood volume was determined using Cr5I labelled erythrocytes and indocyanine green (ICG). Prior to measurement of ICG in blood with a spectrophotometer, the blood was hemolyzed with Triton-X. A close correlation of r = 0.97 between the Cr51 and the ICGTR-X estimates was found; the ICGTR-X volume was about 3% lower than the Cr51 volume. In five additional in vitro experiments the ICGTR-X method was found to reflect real volumes with an insignificant error of less than 1%. Blood volume determination with ICGTR-X cannot be applied in cases of circulatory failure. ICG should be administered in a dose of 0.5 mg/kg of body weight. For calibration purposes, a two point calibration curve (point 1: point of intersection of x and y axis; point 2: 5 mg ICG/1 of blood) is sufficient. From these preliminary experiments it is concluded that the ICGTR-X method is a rapid and simple technique of blood volume determination with multiple reproducibility which can be carried out in any clinical laboratory. PMID- 2308474 TI - Morphine metabolism in the naturally morphine-tolerant afghan pika: a preliminary study. AB - The afghan pika (Ochotona rufescens), a lagomorph which is naturally tolerant to the analgesic action of morphine, metabolizes morphine into morphine 3 glucuronide apparently faster than does the rabbit, another lagomorph which is however normally responsive to morphine. In the two species, following morphine administration, another unidentified component appears very soon (5 min) in pika blood plasma and much later (60 min) in rabbit blood plasma. This unknown component which appears not to be morphine derived might be involved in the natural resistance of the Afghan pika to morphine. PMID- 2308475 TI - Sirius red histophotometry and spectrophotometry of sections in the assessment of the collagen content of liver tissue and its application in growing rat liver. AB - By means of staining with Sirius Red F3BA in a saturated picric acid solution, the collagen contents of rat livers with varying degrees of fibrosis have been measured quantitatively in fixed and sectioned material, using both histophotometry in situ and extraction of bound dye with colorimetric analysis. These findings have been correlated with chemical assays of the hydroxyproline content in homogenates from the same livers. It appears that a highly significant correlation exists between both section-based analysis methods and the hydroxyproline content, the Spearman-Rank correlation coefficients being virtually identical. For analysis of collagen accumulation in rat liver, both section-based methods seem to be useful and reliable, the extraction method giving the quickest results for large-scale screening, and the histophotometric method being more appropriate to take readings in selected areas. With human liver material, indications have been obtained for the existence of large sampling errors due to inhomogeneous distribution of collagen deposits. Using the extraction method, no significant changes could be observed in the volume density of collagen during postnatal growth from 1 week to 21 months in rat liver: only on the third day after birth was a higher value of collagen/total protein obtained, possibly due to a higher water content of the hepatocytes. Partial hepatectomy was found to have no influence at all on the collagen content of rat liver during the period of restorative growth or after it. PMID- 2308476 TI - Effect of parathyroid hormone on portal pressure in portal hypertensive rats. AB - Conflicting results have been common in the pharmacological treatments of portal hypertension. In an attempt to seek better management of portal hypertension, we studied the effect of the synthetic parathyroid hormone (PTH) fragment, [bPTH-(1 34)], in portal hypertensive rats (partial portal vein ligation). PTH, 10 U/kg, administered via the jugular vein resulted in a reduction of both mean arterial blood pressure (MAP) and portal pressure (PP) to a similar extent (18.9% and 16.9%, respectively). A higher dose (40 U/kg) of PTH lowered the PP by 27.8% and MAP by 43.2%. Hemodynamic experiments, performed with labelled microspheres, demonstrated that PTH decreased the blood flow of the splanchnic and hepatic portal collateral vascular beds. To determine whether there is a direct vasodilatory effect on the venous vasculature, the effect of PTH on the isolated portal vein was examined. PTH was capable of inhibiting both spontaneous and drug (methacholine 10(-7) mol/l or KCl 40 mmol/l-induced contraction in a dose dependent manner. Therefore, it can be assumed that some of the effect of PTH on portal pressure is due to a selective effect on the portal vein. PMID- 2308477 TI - Immuno-light and electron microscopic features of chronic hepatitis D. AB - A morphologic study with immunohistochemical detection of the viral antigens of hepatitis B and Delta was performed on 36 liver specimens from patients with delta positive chronic viral hepatitis B. Electron microscopy was performed in 9 cases. No light microscopic or ultrastructural features specific for hepatitis D were observed. Lymphocytic infiltration occurred more often close to hepatocytes containing either hepatitis Delta antigen or hepatitis B core antigen in the cytoplasm, suggesting an involvement of cellular immune mechanisms in chronic hepatitis D as well as in hepatitis B. The simultaneous expression of both HBcAg and Delta antigen in occasional specimens over longer time periods indicates the possible co-existence of both viruses without mutual inhibition. PMID- 2308478 TI - Comparative sequential changes in serum and biliary levels of bile acid components after a single dose of D-galactosamine or partial hepatectomy in the rat. AB - In order to characterize changes in bile acid profile during liver cell damage and regeneration, levels of bile acids in serum and bile were determined by high performance liquid chromatography (HPLC) in F344 rats treated with a single dose of D-galactosamine (galactosamine, 300 mg/kg, i.p.) or subjected to two-thirds partial hepatectomy (PH). In the serum, galactosamine caused elevation of conjugated bile acids such as taurocholic acid (TCA) and tauro-beta-muricholic acid (T beta MCA) at the 24 and 48-h time points, whereas unconjugated bile acids including cholic acid (CA) at 24 h and hyodeoxycholic acid (HDCA) at 48 h were increased after PH. In the bile, elevation of TCA showed most remarkable elevation at the 24-h time point in the galactosamine-treated group. All components of biliary bile acids showed rapid decreases from 24 to 48 h. The results demonstrated that while liver tissue damaged by galactosamine is able to conjugate bile acids it allows leakage into the blood stream. In contrast, the results for rats subjected to PH indicated that liver cells during DNA synthesis are not capable of conjugating all free bile acids with taurine although a similar leakage occurs. It is concluded that obvious elevation of serum TCA or CA and biliary T beta MCA could be a useful indicator of hepatocellular proliferation. PMID- 2308481 TI - Persistence of hepatitis B virus DNA after serological clearance of hepatitis B virus. AB - Using Southern blot technique, the state of hepatitis B virus (HBV) DNA in liver tissue was investigated in 16 patients who were sero-negative for hepatitis B surface antigen (HBsAg) but positive for its antibody (anti-HBs). In only one case, was HBV DNA found in liver tissue in a heterogeneously integrated form. In this case, digestion with Taq I demonstrated integrated HBV DNA as two definite bands at 1.8 and 0.5 kbp. This suggests that HBV DNA in some cases persists even after HBV infection has been cleared serologically. It is possible that this persistence of HBV DNA plays an important role in hepatocarcinogenesis. PMID- 2308480 TI - Reactivation of viral replication in anti-HBe positive chronic HBsAg carriers. AB - Reactivation of hepatitis B virus replication was investigated in an unselected group of 44 HBV DNA negative, anti-HBe positive chronic HBsAg carriers. Twenty five patients (54%) were intravenous drug addicts and 7 (16%) were male homosexuals. Sixteen patients had evidence of delta infection and five of the seven male homosexuals had human immunodeficiency virus infection. The patients were followed for 1 to 180 months (median, 24 months) while HBV DNA negative, anti-HBe positive. Reactivation, defined as reappearance of HBV DNA or HBeAg, or both, was detected in six patients corresponding to an annual reactivation rate of 5%. Reactivation in four patients was detected by reversion to HBV DNA positivity only, whereas HBeAg/anti-HBe status remained unchanged. Two patients became both HBV DNA and HBeAg positive. None of the patients developed hepatitis like symptoms and transaminase elevation was only observed in two patients. Reactivation in two patients was ascribed to human immunodeficiency virus infection and in one patient to chronic lymphatic leukaemia. It is concluded that HBV DNA seems to be superior to HBeAg in the detection of reactivation of HBV replication and that reactivation associated with clinical symptoms leading to progression in chronic liver disease is a rare event in the population studied. PMID- 2308482 TI - SMRI. Society for Magnetic Resonance Imaging. Eighth annual meeting. February 24 28, 1990, Washington, D.C. Abstracts. PMID- 2308479 TI - Evidence for the involvement of organelles in the mechanism of ketone-potentiated chloroform-induced hepatotoxicity. AB - Ketones can potentiate the hepatotoxicity of haloalkanes in animals. This may be due, in part, to changes in organelle susceptibility. Male Sprague-Dawley rats were administered 15 mmol/kg (po) acetone, 2-butanone, 2-hexanone or 50 mg/kg (po) chlordecone or mirex (a nonketonic analog of chlordecone). Eighteen hours later, tests of organelle structure/function were performed (osmotic stress, respiration, and calcium pump activity). Other rats were given 14CHCl3 (0.5 or 1.0 ml/kg, po) 18 h after chlordecone or mirex administration. Three hours later, the organelle distribution of 14C was evaluated. In a final experiment, ketone pretreated (chlordecone or 2-hexanone) animals were killed 6 h after CHCl3 administration and evaluated morphologically for evidence of modified organelle response. Acetone and chlordecone, when given alone, enhanced lysosomal fragility to osmotic stress; no changes in functional capacity of mitochondria or microsomes were observed. CHCl3-derived 14C in the mitochondrial fraction increased 2-fold in chlordecone-treated rats. Morphological evaluation suggested mitochondria respond differently to CHCl3 in ketone-pretreated (chlordecone or 2 hexanone) animals compared to corn oil-pretreated controls. These results support the concept that modifications of organelles contribute to the mechanism of ketone-potentiation of CHCl3-induced hepatotoxicity. PMID- 2308483 TI - Inflammatory carcinoma of the breast: Part II. PMID- 2308485 TI - Med Chi ... our best defense in Annapolis. AB - Last September Med Chi's Council entered into a five-year contract with the law firm of Rifkin, Evans, Silver, and Lamone. The contract requires the firm to provide legislative and legal advice on all matters facing the Faculty. PMID- 2308484 TI - Antitrust's recent attack on the peer review practitioner: is the Health Care Quality Improvement Act a viable remedy? AB - Peer review, an increasingly important function in the hospital setting, is unique in that physicians are granted the task of evaluating and supervising the actions of their counterparts. Regardless of the consequences resulting from the peer-review system now operating within the hospitals, it will continue to be a mainstay until a more workable alternative is proved successful. PMID- 2308486 TI - A.I.D.S. PMID- 2308487 TI - Cholesterol testing. PMID- 2308488 TI - Prescription drug control and dispensing. AB - This paper is formulated to discuss the issues of prescription drug control and dispensing, particularly as it relates to the problem of drug abuse in general, which is the purview of the Committee on Drugs, The issues are several: 1. The large morbidity and mortality associated with the use of prescription and nonprescription drugs in this country. 2. The issue of recreational use of drugs, most important numerically being alcohol, and the many other drugs which are both licit and illicit, primarily illicit. 3. The issue of drug addition and how to prevent and treat it. 4. The issue of law enforcement with regard to both illicit drugs and the diversion of licit drugs and the increasing mortality associated with the trafficking and law enforcement of drug abuse. 5. The issue of restricting the rational use of medicines. The question of whether a governmental system which totally proscribes certain drugs and provides extreme restrictions on the prescription of others will reduce deaths and morbidity is an open one. There seems little doubt that our country has extremely prohibitive and restrictive laws and yet has a huge mortality associated with distribution networks of illicit drugs and also more than ten thousand deaths a year from drug overdose. PMID- 2308489 TI - The problem of the uninsured. PMID- 2308490 TI - January 1990. Current treatment guidelines for sexually transmitted diseases. PMID- 2308491 TI - The epidemiology of AIDS in Maryland, 1981-1987. AB - From 1981 through 1987, a total of 1,068 AIDS cases were diagnosed in Maryland; 62.8 percent occurred in the homosexual/bisexual male cohort followed by intravenous drug abusers, 21.8 percent. Time trends suggest that proportionally fewer cases of AIDS will occur among homosexual/bisexual males and transfusion patients, and more cases will appear among intravenous drug abusers and heterosexuals. PMID- 2308492 TI - Diabetic retinopathy. PMID- 2308493 TI - [Approaches to the individual prognosis of tumor reaction to radiation and drug exposures]. AB - The problem in individual prediction can be viewed in two aspects: 1. to define the nature of tumor response to antitumor therapy; 2. to determine whether a specific therapeutic method is sufficient for a patient's cure. Individual prediction cannot solve the problem of therapy of cancer patients, however it will noticeably improve the results of routine cancer therapy and will help to use correctly uncommon therapeutic methods. The choice of patients with radioresistant malignant tumors out of the whole population will enable one to select correctly radiomodifiers. PMID- 2308494 TI - [The absorbed dosage and its fractionation in the radiation treatment of tumors in children]. AB - Radiation therapy is widely used in pediatric oncology. Its use emphasizes the problems of the protection of growing tissues and organs. The paper is concerned with the problem of effective distribution of an ionizing radiation dose delivered to a locally advanced tumor in children. Analysis of the literature and authors' data show that the growing organs of a child are 2-2.5-fold more sensitive than the same organs of an adult. Besides some organs and tissues at various ages of a child possess a various degree of maturity. Therefore it is proposed that small single doses (0.6-1 Gy) that can be delivered 2-3 times a day, should be used in pediatric oncology. A scheme of dynamic irradiation of radiosensitive and resistant tumors of children was prepared and tested under clinical conditions. PMID- 2308495 TI - [The efficacy of gamma teletherapy in the combined treatment of medulloblastomas in the posterior cranial fossa of children]. AB - The results of radiation therapy conducted after various schemes were compared in 77 patients operated on for medulloblastoma of the posterior cranial fossa: 1. irradiation of the posterior cranial fossa area; 2. irradiation of this area and the entire length of the spinal marrow; 3. total irradiation of the CNS. Stages in a metastatic process necessitate irradiation in stages, i.e. irradiation of the posterior cranial fossa and the length of the spinal marrow followed by irradiation of the cerebral hemispheres one year after the operation. Total irradiation of the CNS shortly after the operation is recommended only in the presence of early metastases. PMID- 2308496 TI - [The effect of normobaric hypoxia on the functioning of links in the endocrine system]. AB - The paper is concerned with the data on change in the blood level of ACTH, STH, TSH, cortisol, T3, insulin, C-peptide during a 25-minute session of respiration using a gaseous hypoxic mixture with 10% oxygen (GHM-10). The investigation was performed in 23 healthy volunteers. Change in the hormonal status, characteristic of a moderate stress-reaction, was observed in 60% of the examinees. It was found out that during a GHM-10 session a degree of change in function of the studied factors of the endocrine system showed correlation with change in the activity of the autonomic nervous system. PMID- 2308497 TI - [The myocardial function of the left ventricle in hypertension based on data from radionuclide ventriculography]. AB - Radionuclide ventriculography was used in 145 patients with stage I and II essential hypertension and in 20 healthy persons to investigate systolic and diastolic function of the left ventricular myocardium. Quantitative analysis of myocardial function was performed on the basis of indices of total and local contractility, cardiac output, time and rate values of contraction and filling. A decrease in total ejection fraction, rate values of contraction and filling combined with increased cardiac outputs was noted in stage II essential hypertension. An exercise tolerance test in some of these patients revealed signs of the limited myocardial reserve. PMID- 2308498 TI - [The microcirculatory reorganization of the lesser circulation during the rehabilitation of myocardial infarct patients]. AB - A study was made of the regional distribution of the pulmonary blood flow by means of perfusion scintigraphy of the lungs with 99mTc-albumin macroaggregates with relation to a clinical course of CHD, the state of intracardiac and pulmonary hemodynamics. The time course of microcirculation in the lesser blood flow during rehabilitation of patients after myocardial infarction was assessed. Redistribution of the pulmonary blood flow was shown to be connected with the clinical features of a course of CHD, severity of myocardial lesion, and a degree of disorder of intracardiac and pulmonary hemodynamics. Therefore these changes can be of important prognostic value in patients after myocardial infarction. PMID- 2308500 TI - [A method for calculating the distribution in biological tissue of an absorbed dose of a fast-neutron beam from the U-120 cyclotron]. AB - The author proposed a method for calculation of the distribution of an absorbed dose of a fast neutron beam on Y-120 cyclotron in biological tissue. The method ensured the coincidence of the results with average experimental data with the accuracy no less than 3%, and could be used for dosimetric design of cancer therapy with fast neutrons. PMID- 2308499 TI - [241Am body distribution in dogs after its intravenous administration and early complexon therapy]. PMID- 2308501 TI - [Aneurysmal bone cyst of the visceral cranium]. PMID- 2308502 TI - [A statement by a group of scientists working in the field of radiation safety and radiation medicine in connection with the situation caused by the accident at the Chernobyl Atomic Electric Power Station]. PMID- 2308503 TI - Maryland MIRRORS/II: a connectionist model simulator. AB - Developing and evaluating connectionist models (also called neural models) is a difficult and time-consuming task. To address this issue, we designed a software system called Maryland MIRRORS/II for the construction of connectionist models in biomedicine and other fields. Maryland MIRRORS/II is distinguished from previous and current related systems by its support of a high-level nonprocedural language, a general-purpose event-handling mechanism, and an indexed library of system resources. These features make Maryland MIRRORS/II a convenient software tool for use in biomedicine. This paper describes Maryland MIRRORS/II and provides a simple example in which it uses error back propagation learning to select the appropriate treatment for a given set of manifestations. PMID- 2308504 TI - Computer-assisted soliloquy as an approach to psychotherapy. AB - Schools of talking therapy generally consider the doctor-patient relationship to be essential to the therapeutic process. Yet studies reveal that the presence of a therapist can sometimes inhibit frank disclosure and that patients will speak alone, in the absence of a therapist, about matters of importance to them. We have programmed a computer interview to facilitate soliloquy and have studied its effectiveness. Encouraged by the computer, subjects talked into a microphone first about anxiety-provoking circumstances and then about relaxation. Both mean heart rate and State anxiety scores fell significantly between the beginning and the end of the interview. PMID- 2308506 TI - Current Contents on Diskette and Reference Update. AB - Both Current Contents on Diskette and Reference Update provide an excellent mechanism for keeping abreast of the biomedical literature with a personal computer. Both systems are compatible with the two major database management programs for manipulating reprint files. Reference Update exports directly to Reference Manager (a choice on the main menu). Exporting to a file can also be done with one of four formats: Table of Contents, MEDLINE, Full, and One Line. To export Reference Update records into Pro-Cite, for example, the records must first be downloaded into MEDLINE format. Current Contents on Diskette also exports in four different formats: MEDLINE, Comma Delimited, Screen Image, and DIALOG. MEDLINE corresponds to Reference Manager format, and Comma Delimited corresponds to Pro-Cite format. Both products include reprint request systems that can be used directly from the programs. The two products share many features and differ primarily in terms of journal coverage. Current Contents on Diskette provides document delivery by means of the Genuine Article service, and Reference Update offers a synonym feature. Both programs are attractive alternatives to manual or on-line searching of the biomedical literature. PMID- 2308505 TI - Lessons from a doctoral thesis. AB - The production of a doctoral thesis is a time-consuming affair that until recently was done in conjunction with professional publishing services. Advances in computer technology have made many sophisticated desktop publishing techniques available to the microcomputer user. We describe the computer method used, the problems encountered, and the solutions improvised in the production of a doctoral thesis by computer. The Apple Macintosh was selected for its ease of use and intrinsic graphics capabilities. A scanner was used to incorporate text from published papers into a word processing program. The body of the text was updated and supplemented with new sections. Scanned graphics from the published papers were less suitable for publication, and the original data were replotted and modified with a graphics-drawing program. Graphics were imported and incorporated in the text. Final hard copy was produced by a laser printer and bound with both conventional and rapid new binding techniques. Microcomputer-based desktop processing methods provide a rapid and cost-effective means of communicating the written word. We anticipate that this evolving technology will have increased use by physicians in both the private and academic sectors. PMID- 2308507 TI - Neural networks in plants? PMID- 2308508 TI - The Larry P. decision a decade later: problems and future directions. PMID- 2308509 TI - Reactions of black, Hispanic, and white mothers to having a child with handicaps. AB - Black, Hispanic, and white mothers (N = 60) of young children with disabilities were interviewed to explore their feelings and reactions to their child. Trends reveal that Hispanic mothers reported an attitude of self-sacrifice toward the child and greater spousal denial of the disability more often than did the other mothers. Stages of reaction from strong negative feelings to later periods of adjustment were most often reported by both Hispanic and white subjects. Although severity of retardation was not predictive of parental reporting of stages, parents of children who received a diagnosis within a month of birth were more likely to report subsequent adjustment stages. PMID- 2308510 TI - "Excuse me: I'll have...": teaching appropriate attention-getting behavior to young children with severe handicaps. AB - Procedures to teach two young children with severe handicaps to get an adult's attention when needing to make a request were developed. Both children were already capable of making requests in the presence of an adult, but not capable of getting the attention of the adult if not in close proximity. Both children acquired the response of getting out of his or her seat, walking over to the adult in the classroom, and exhibiting appropriate attention-getting behavior after training. This behavior maintained at a 3-week follow-up. PMID- 2308511 TI - Impact of interdisciplinary team review on psychotropic drug use with persons who have mental retardation. AB - The process of medication and behavior review used at the Wyoming State Training School was described. The review team, a multidisciplinary group that included representatives from medicine, psychology, and residential living, examined each resident's entire regimen of medications every 6 months, with emphasis on psychotropic medications. Data on psychotropic drug usage in the individual patient was correlated with graphs indicating frequency of target behaviors. The goal was to find the least restrictive method of behavior management, evaluating effectiveness of medications and reducing dosages whenever possible. Significant reductions in use of psychotropic medications since 1979 was documented. Cost savings were also noted. PMID- 2308512 TI - Training and education of persons with disabilities in the Soviet Union: report by a Very Special Arts delegation. PMID- 2308513 TI - Integrating children with severe disabilities for intensified outdoor education: focus on feasibility. AB - The feasibility of an intensified (i.e., all-day-for-2-weeks) integrated camping experience for children with and without severe disabilities was evaluated as was the impact of integrated programming on camp staff members' attitudes. Procedures employed for promoting social interactions included positive reinforcement and cooperative learning strategies. Task-analytic procedures were used to teach campers with severe disabilities a domestic skill and a life-long leisure activity. By the end of the 2 weeks, children with severe disabilities demonstrated substantially improved skills in targeted activities. Furthermore, campers without disabilities substantially increased their prosocial interaction bids, and ratings reflective of friendship increased significantly. Also, staff members' perceptions of operating an integrated camp versus a segregated one and their perceptions of the presence of participants with disabilities as facilitative of camp operations improved significantly. PMID- 2308514 TI - Dietary fish oils limit adipose tissue hypertrophy in rats. AB - Total body mass, fat pad mass, and fat cell size were examined after feeding rats diets containing 20% triglycerides from fish oil or lard. Although food consumption, weight gain, and fat balance on the two diets were similar, lard-fed rats had 77% more fat in perirenal fat pads and 51% more fat in epididymal fat pads compared with fish oil-fed rats. There was no difference between the two groups in fat cell number in each region; however, adipocytes were significantly smaller in fish oil-fed rats. Thus dietary fish oil appears to limit triglyceride accumulation in adipose tissue and thereby limit fat cell trophic growth. PMID- 2308516 TI - Influence of thyroid hormones on gluconeogenesis from glycerol in rat hepatocytes: a dose-response study. AB - The role of L-3,3'-5 triiodothyronine (T3), in a pathophysiological range, on gluconeogenesis from low concentration of glycerol (2 mmol/L), was investigated in isolated liver cells from 24-hour fasted rats either thyroidectomized, normal, or treated by a T3 dose ranging from 1, 5, or 10 micrograms/d/100 g body weight (BW) during 3 days to 50 micrograms during 7 days. Gluconeogenesis from glycerol was decreased by 63% in hypothyroid rats and increased by 35% in severely hyperthyroid rats. However, in cells from mild hyperthyroid rats no increase of gluconeogenesis was observed. Nevertheless, in mild hyperthyroidism, alpha glycerophosphate (G3P) was significantly decreased and gluconeogenesis from glycerol was not inhibited by the addition of ethanol (10 mmol/L), both of which have a drastic effect in cells from thyroidectomized rats. The decrease of gluconeogenesis observed in cells from thyroidectomized rats was reversed by the addition of pyruvate (10 mmol/L). Thus, when the cells were in a "reduced state" (addition of ethanol) the differences between the group were magnified, and when the cells were in an "oxidized state" (addition of pyruvate) the differences were suppressed. These findings suggest that alteration of the capacity of reducing equivalents transfer from the cytoplasmic compartment to the mitochondria is the main mechanism by which mild hyperthyroidism can stimulate gluconeogenesis. PMID- 2308515 TI - Plasma lipid transfer activities in hyper-high-density lipoprotein cholesterolemic and healthy control subjects. AB - The relationships between plasma lipid transfer protein (LTP) activity and various lipid or lipoprotein concentrations were studied in 14 hyper-high-density lipoprotein (hyper-HDL) cholesterolemic subjects and 152 healthy controls. We measured plasma LTP activity by our sensitive assay method, using radiolabeled proteoliposomes as the lipid donor, low-density lipoprotein (LDL) as the acceptor, and a very small amount of untreated plasma (typically 1 to 2 microliters) as the sample. Control subjects had the mean of LTP activity at 206 +/- 45 nmol/mL/h. The difference of LTP activity between men and women was not statistically significant. In the control subjects, the activity of plasma LTP had a significantly positive correlation with the concentrations of total cholesterol (r = .639, P less than .01) and LDL cholesterol (r = .634, P less than .01), but not with those of HDL cholesterol and total triglyceride, nor with percent ideal body weight. One of 14 patients with hyper-HDL cholesterolemia had no detectable LTP activity, and three others had very low LTP activity. From these data, LTP activity may be one of the important factors to influence plasma LDL concentration, and the lack of LTP activity may be related to a subclass of hyper-HDL cholesterolemias. PMID- 2308517 TI - Modulation of chylomicron remnant metabolism by an hepatic hydroxymethylglutaryl coenzyme A reductase inhibitor. AB - This study was designed to test the hypothesis that in patients with elevated plasma low-density lipoprotein (LDL) apolipoprotein-apoB, chylomicron remnant clearance can be modulated by therapy with a hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitor. Accordingly, chylomicron triglyceride and remnant clearance were determined following a vitamin-A fat load in 12 such patients, before and after therapy with Lovastatin (Merck, Sharp & Dohme, Rahway, NJ). Such therapy had no significant overall effect on plasma triglyceride clearance, although there was a trend to lower levels of Sf greater than 400 triglycerides at the later time points. By contrast, retinol clearance in plasma and Sf greater than 400 lipoproteins was markedly increased (30% and 40%, respectively). The data indicate, therefore, that following therapy with Lovastatin in this group of patients, chylomicron plasma remnant clearance was significantly enhanced. The exact mechanisms responsible remain to be explicated. PMID- 2308518 TI - A high carbohydrate-fat free diet alters the proportion of heparin-bound VLDL in plasma and the expression of VLDL-apoB-100 epitopes. AB - High carbohydrate-fat free diets (CHO-diet) induce the secretion of increased numbers of very-low-density lipoprotein (VLDL) particles and alter the composition and metabolism of VLDL. The aims of this study were to examine VLDL in greater detail, specifically to document any CHO-diet-induced alterations of apolipoprotein B-100 (apoB-100) epitope expression of VLDL, and any changes induced in subclasses of VLDL, as defined by heparin Sepharose chromatography. Fifteen normolipidemic subjects participated in the study by eating a basal typical American diet for 7 days and high carbohydrate diet (85% carbohydrate, less than 1% fat) for another 7 days. The sequence was changed in seven subjects. Fasting blood samples were analyzed for lipoprotein lipid and apoprotein concentrations. Heparin affinity VLDL subclasses were characterized chemically and electrophoretically [sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE)]. Immunoreactivities of apoB in VLDL were tested in solid phase competitive-binding radioimmunoassays (RIAs) using five monoclonal anti-B antibodies that react with defined epitopes of apoB-100. The CHO diet produced consistent increases of plasma triglycerides in all subjects by a mean of 66% and decreases in plasma cholesterol by 18%. ApoB in plasma decreased by 21% and apoA I by 17%; however, apoE and ApoA-II did not change. VLDL was enriched with triglycerides (55.0% +/- 0.8 v 57.0% +/- 0.7, P less than .05) and apoE (3.7% +/- 0.5 to 5.9% +/- 0.7, P less than .007) and the ratio between apoE and apoC in VLDL increased (0.15 +/- 0.03 to 0.25 +/- 0.03, P less than .002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308520 TI - Measurement of composition changes using dual-photon absorptiometry in obese patients undergoing semistarvation. AB - The changes in total fat mass (TFM) and lean body mass (LBM) under semistarvation treatment were measured by dual-photon absorptiometry (DPA) in this study. Three females with massive obesity were followed over two periods consuming a very-low calorie diet (VLCD). Although LBM changes attributed to water shifts related to sodium balance were observed, DPA proved sensitive enough to measure LBM and TFM changes in semistarvation treatment. LBM measured by DPA did not change significantly following 4 weeks of VLCD. However, TFM decreased significantly (70.9 +/0 24.1 kg to 62.4 +/- 21.7 kg) and paralleled body weight. PMID- 2308519 TI - Glycogen repletion and exercise endurance in rats adapted to a high fat diet. AB - It is well accepted that exercise endurance is directly related to the amount of carbohydrate stored in muscle and that a low carbohydrate diet reduces glycogen storage and exercise performance. However, more recent evidence has shown that when the organism adapts to a high fat diet endurance is not hindered. The present study was designed to test that claim and to further determine if animals adapted to a high fat diet could recover from exhausting exercise and exercise again in spite of carbohydrate deprivation. Fat-adapted (3 to 4 weeks, 78% fat, 1% carbohydrates) rats (FAT) ran (28 m/min, 10% grade) as long as carbohydrate fed (69% carbohydrates) animals (CHO) (115 v 109 minutes, respectively) in spite of lower pre-exercise glycogen levels in red vastus muscle (36 v 54 mumols/g) and liver (164 v 313 mumols/g) in the FAT group. Following 72 hours of recovery on the FAT diet, glycogen in muscle had replenished to 42 mumols/g (v 52 for CHO) and liver glycogen to 238 mumols/g (v 335 for CHO). The animals were run to exhaustion a second time and run times were again similar (122 v 132 minutes FAT v CHO). When diets were switched after run 1, FAT-adapted animals, which received carbohydrates for 72 hours, restored muscle and liver glycogen (48 and 343 mumols/g, respectively) and then ran longer (144 minutes) than CHO-adapted animals (104 minutes) that ate fat for 72 hours and that had reduced glycogen repletion. We conclude that, in contrast to the classic CHO loading studies in humans that involved acute (72 hours) fat feedings and subsequently reduced endurance, rats adapted to a high fat diet do not have a decrease in endurance capacity even after recovery from previous exhausting work bouts. Part of this adaptation may involve the increased storage and utilization of intramuscular triglycerides (TG) as observed in the present experiment. PMID- 2308521 TI - Hematoporphyrin can inhibit the metabolism and growth of embryonic chicken cartilage in vitro. AB - Hematoporphyrin (HP) derivatives have been recognized chiefly as growth inhibitors of neoplastic tissues within the context of tumor phototherapy. We investigated the possibility that HP may also modify the growth potential of rapidly growing nonneoplastic tissues and describe the effect of HP on the metabolism and growth of embryonic chick cartilage in vitro. In the embryonic chick pelvic rudiment prolonged organ-culture bioassay, pelvic rudiment growth was significantly inhibited when HP 0.01 mmol/L was added to the culture medium (after 5 days in organ culture, weight increment in presence of serum + 136% +/- 12% v + 90% +/- 8% in presence of serum plus HP 0.01 mmol/L and + 43% +/- 10% in presence of serum plus HP 0.025 mmol/L, P less than .001). Inhibition of cartilage growth was irreversible if HP was added to the culture medium without serum for 2 days, but partial reversibility was observed when hypophysectomized rat serum was present during that period. Therefore, the protective effect of serum was apparently unrelated to pituitary-dependent growth factors. Binding of HP to albumin did not eliminate its inhibitory effects. Uridine incorporation into RNA and, to a lesser extent, sulfate incorporation into proteoglycans were reduced in cartilage incubated overnight with HP. Our study shows that HP can exert partially reversible inhibition of cartilage metabolism and growth suggesting potentially novel tissue actions for this compound. PMID- 2308522 TI - On the measurement of pathways of glycogen synthesis. PMID- 2308523 TI - Hepatic glucose-6-phosphate cycling has no bearing on recently used isotopic procedures to investigate the pathways of glycogen synthesis. PMID- 2308524 TI - Comparative diagnostic performance of three radiological procedures for the detection of lumbar disk herniation. AB - Literature data on the diagnostic performance of phlebography, myelography, and CT scan applied to patients with suspected lumbar disk herniation (LDH) are analyzed to extract maximal information about their relative discriminatory power. Seventeen papers meeting the selection criteria contain 13 reports on myelography, 6 on phlebography, and 5 on CT. Sensitivity and specificity are considered simultaneously in logistic ROC space. The reports of each procedure are effectively summarized by a linear regression in logistic ROC space. Taking into account the individual confidence regions of sensitivity and specificity obtained from each report, the slope of the regression line is estimated by Generalized Least Squares (ML). This approach also allows to test the assumption of a common odds ratio (i.e., of a unit slope). The simply to determine common odds ratio as well as the perpendicular distance between the origin and the regression line (as a good approximation to the area under the ROC curve) are used as a measure for the discriminatory power of the procedures. For CT, homogeneity of sensitivity turns out to be much more likely than a common odds ratio. Based on the available, retrospective data, phlebography appears to have the highest performance in visualizing an LDH, followed by myelography and CT. PMID- 2308525 TI - Data-screening and retrieval of medical data by the system WAREL. AB - The paper presented here deals with the computer system WAREL, a system for analyzing medical patient data. It is a patient-oriented medical data-screening system which automatically points out medical risk factors. Referring to all patients, it is a retrieval system for selecting groups of patients from the clinical data base; the explorative statistical analysis concerning medical data of these selected groups can give an essential impulse to clinical research. The most important components of the system such as the relational data base and the system for defining and activating logical conditions are discussed. These conditions (IF-THEN rules) are the basis of both the patient oriented data screening and the retrieval of patient groups. They may refer to data in formatted or in natural language form; furthermore conditions of the course of illness can also be formulated. Thus, the data-screening system may also indicate risk situations due to the course of an illness. PMID- 2308526 TI - Development of an instrument for the management of computer user attitudes in hospitals. AB - Measuring and managing user attitudes toward various aspects of computer systems is an important part of making those systems effective. In this paper, results of an effort to adapt and test a technique for measuring user satisfaction in hospitals are presented. These results include extensive empirical tests of the technique. Comparison norms for hospital computer user satisfaction are also presented and interpreted. Analysis software for using the technique as a management tool is presented. Finally, experiences using the concept are presented. PMID- 2308527 TI - Detecting hidden relations between time series of mortality rates. AB - In the present report a method is described which may help to decide if a disease is influenced by an environmental factor which fluctuates in time: For each of two naturally arising subgroups of a population (such as males and females) an ARIMA model (autoregressive integrated moving average model) is identified. These models are used as filters to remove the autocorrelation in each series. If the resulting crosscorrelation function between the two filtered series shows a marked peak at time lag 0 this may indicate that such an environmental factor is present. The procedure is demonstrated using yearly data of mortality rates among the elderly. PMID- 2308528 TI - Information content of diagnostic tests in the medical literature. AB - Diagnostic tests provide information about the presence or absence of disease. However, even after application of diagnostic tests, significant uncertainty about the state of the patient often remains. This uncertainty can be quantified through the use of information theory. The "information" contained in diagnostic tests published in the medical literature of the years 1982 through 1986 was evaluated using Shannon information functions. Information content, averaged over all prior probabilities of disease, ranged from 0.002 bits to 0.720 bits of information; the tests therefore provided from 0.3% to 100% of the information needed for diagnostic certainty. Median average information was 0.395 bits, corresponding to only 55% of the information required for diagnostic certainty. Reclassifying test results into multiple mutually exclusive outcome categories allowed extraction of a median of 14% and a maximum of 109% more average information than that obtained using a dichotomous positive/negative classification. We conclude that the "information" provided by many of the tests published in the medical literature is insufficient to overcome diagnostic uncertainty. Information theory can quantify the uncertainty associated with diagnostic testing and suggest strategies for reducing this uncertainty. PMID- 2308529 TI - Isolation and antimicrobial susceptibility of Campylobacter coli and Campylobacter jejuni from slaughter hogs. AB - Cultural examination of cecal contents from 109 market weight hogs slaughtered in Prince Edward Island during May-July 1988 yielded 62 isolates of Campylobacter coli and seven Campylobacter jejuni. A commercial latex agglutination test helped to confirm the identification of Campylobacter. When tested against four drugs: erythromycin, tetracycline, kanamycin and ampicillin, 11 isolates showed multiple resistance. Resistance to erythromycin was seen in 19% and 28.6% of Campylobacter coli and Campylobacter jejuni respectively. All the isolates were susceptible to nitrofurans, gentamicin and chloramphenicol. PMID- 2308530 TI - Cholera-like enterotoxin in certain Campylobacter jejuni strains: some observations. AB - Fourteen human isolates of Campylobacter jejuni (13 pathogenic + 1 non pathogenic) and two animal isolates were studied for the production of a toxin immunologically related to the heat-labile enterotoxin (LT) produced by a strain of Escherichia coli of human (H) origin using an immuno-dot-blot assay with immunoaffinity purified antibodies against H-LT. Polymyxin-B sulfate extracts of 72 hrs growth in eight of the 15 pathogenic strains were positive in immuno-dot blot. Six of these positive extracts also exhibited delayed permeability factor activity in rabbit skin. PMID- 2308531 TI - Fusarium peritonitis in peritoneal dialysis: report of two cases. AB - This report describes two cases of peritoneal dialysis-related peritonitis caused by Fusarium species which have been incriminated in a variety of disease conditions. Treatment with 5-Fluorocytosine was unsuccessful, but removal of the catheter resulted in a rapid resolution of the infections. PMID- 2308532 TI - Survival of Borrelia burgdorferi in different electroporation buffers. AB - Electroporation consists in the application of an electric field through a cell membrane until the membrane itself develops transient pores. This technique has been used to insert external macromolecules into both eukaryotic and prokaryotic cells. In this study we investigated the survival ratio of Borrelia burgdorferi, the Lyme disease spirochete, under different electroporation conditions. PMID- 2308533 TI - Adolescents & AIDS. An outlook for the 1990s. PMID- 2308534 TI - Adolescents & AIDS. Three Michigan physicians reach out to educate youth about AIDS/HIV. AB - Three Michigan doctors are taking promising new approaches to bring home the tough health care issues facing adolescents in the 1990's--most importantly, AIDS. All three approaches, which range from a school-based clinic to a questionnaire, attempt to solve specific, and difficult problems--like HIV infection--by improving the broader health care education and treatment needs of all adolescents. Only one of the approaches singles out HIV infection as its sole target. But all three provide new avenues to deal with this problem--avenues adolescents are willing and capable of traveling. PMID- 2308535 TI - MSMS offers a physician's guide to AIDS/HIV in Michigan. PMID- 2308536 TI - Competition. Here's what physicians can do to meet it. PMID- 2308537 TI - Sen. Richard Posthumus. A fighter for West Michigan. PMID- 2308538 TI - PROM. Physician's Review Organization of Michigan. An unbiased voice for patients. PMID- 2308539 TI - Measurement of dose distributions of linear energy transfer in matter irradiated by fast neutrons. AB - A detector has been developed and used to measure dose distributions versus linear energy transfer to thin gas targets in spherical geometry from fast neutron irradiation of tissue-equivalent plastic and carbon. The detector is a hemispherical proportional counter with a Cs(T1) scintillator at the center of the hemisphere. The coincidence of the proportional counter signals constrain the measurements to charged particles traversing the radius of the hemisphere. The charged particle energy deposition distributions are directly measured for a known pathlength. The A-150 kerma factor was measured at a neutron energy of 14.8 MeV and is in agreement with tabulated values. The carbon kerma factor measurements are less than the tabulated value at 14.8 MeV. The alpha-particle production in carbon was measured for neutron energies from 14.1 to 14.8 MeV and is compared with existing data. PMID- 2308540 TI - A quality assurance program for monitor unit calculators. AB - A quality assurance protocol has been developed to assess the relative accuracy of computerized monitor unit calculations. Results from this testing reveal that errors (defined as the difference between the computer results and those obtained using a standard formula with manual calculation) in monitor unit calculators are possible when they are tested over a wide range of clinically relevant field sizes (including blocked fields), source-to-surface distances, and depths. It is suggested that computerized monitor unit calculators be checked against hand calculations and that this be permanently documented both at the time of initial implementation and following any subsequent changes in the program. PMID- 2308541 TI - Evaluation of analog contrast enhancement and digital unsharp masking in low contrast portal images. AB - An experimental high-contrast sensitivity storage phosphor imaging system was used to produce double-exposure localization portal images of abdominal and pelvic treatment fields. The images were contrast enhanced by using an analog windowing technique and edge enhanced with a digital unsharp masking routine. A laser printer was used to print the storage phosphor images onto film. Conventional images were obtained by placing film in the cassette with the storage phosphor plates prior to exposure. Four radiation oncologists rated the storage phosphor and conventional films for perceptibility of anatomical detail needed to verify the placement of the treatment field. Contrast enhancement alone did not result in a significant improvement in perceptibility over unprocessed conventional film (p greater than 0.20). However, the combination of contrast and edge enhancement did result in a significant improvement over conventional film (p less than 0.05). PMID- 2308542 TI - A method for obtaining an approximate Wiener filter. AB - The Wiener restoration filter yields the minimum mean-square error between the restored image and the true object function. However, it has found limited use because, in its usual formulation, it requires information about the object power spectrum which is generally unknown. In this paper, it is shown that the Wiener filter can be derived from the noise-free image power spectrum, and a method is presented for estimating this from the observed data. From this estimate an approximate Wiener filter was calculated. The method was tested on three sets of simulated data which included a constant background, rectangular defects, and Gaussian defects at varying contrast and noise levels. The performance of the approximate Wiener filter was compared both to the true Wiener filter and to the standard 1-2-1 three-point smooth. The results confirmed that the approximate Wiener filter adapted to the information content of the observed data and closely matched the performance of the true Wiener filter. The approximate Wiener filter outperformed the three-point smooth in all cases, especially at low contrast and high noise levels. The approximate Wiener filter can be calculated without operator intervention and requires little additional computation time over conventional Wiener filter techniques. PMID- 2308544 TI - The influence of grid size on accuracy in radiotherapy dose plotting. AB - The recent article by Niemierko and Goitein [Med. Phys. 16, 239-247 (1989)] illustrates well the errors which are occurring in plotting isodose lines. We wish to augment their analysis with similar work done at Cardiff a few years ago; to indicate some practical treatment outcomes they have omitted; to propose even more stringent requirements of the grid size used; and thus to further alert users and software manufacturers to this problem. PMID- 2308543 TI - Rapid measurement of T1 with spatially selective pre-inversion pulses. AB - A method is described for rapidly obtaining a multipoint estimate of T1 from a sample that is homogeneous over a few millimeters. An image of the longitudinal recovery curve is produced through the application of successive "pre-inversion" slices that are perpendicular to the imaging slice. These pre-inversion pulses are analogous to pre-saturation pulses, but they are much thinner and the tip angle is 180 degrees. The baseline for the recovery is measured from sections of the sample that have not been perturbed by the slice selective pre-inversion pulses. The existence of the baseline value and the lack of slice profile effects allows a quick T1 estimate (QT1) to be made with a simple linear regression algorithm. The QT1 values are found to correlate very well with T1 values measured with the scanner in "spectrometer' mode, for volumes as small as 5 x 5 x 5 mm. Possible applications are T1 estimates in homogeneous samples and tissues, and scouting the T1 range of a tissue to be measured with higher resolution volume localization techniques. PMID- 2308545 TI - An algorithm for generation of implant plans for high-dose-rate irradiators. AB - An algorithm is described for generating a treatment plan with minimal input from the user for a remote high-dose-rate afterloading irradiator. The algorithm generates a plan after locating all catheters involved and an area of interest on each catheter, and two additional numbers are specified: a radial distance and a target dose. The treatment volume becomes the locus of all points that are within the specified radial distance from any point within the area of interest on any catheter (except for the end points). For a single catheter, the volume may be alternately outlined on an x-ray film of the implant. The routine uses a linear programming formulism to compute which dwell positions are to be used, as well as the dwell time at each position, to irradiate the treatment volume to the target dose while minimizing the total volume integrated dose to the patient. PMID- 2308546 TI - Transillumination imaging performance: spatial resolution simulation studies. AB - Monte Carlo calculations were used to simulate the propagation of visible and near-infrared light through homogenous tissue in order to quantitate the potential spatial resolution performance for transillumination imaging. Specifically, the relative effectiveness of coaxial collimation and time of flight (TOF) detection for improving spatial resolution was investigated. The results demonstrate that significant improvements in spatial resolution can be achieved through these techniques, with TOF methods offering superior performance for a given level of detected signal intensity. PMID- 2308547 TI - Wiener noise power spectra of radiological television systems using a digital oscilloscope. AB - Measurement of spatial noise power spectra from television based radiographic and fluoroscopic systems is essential to the understanding of their operation and optimization. However, conventional methods require acquisition and processing of large numbers of complete images, thus confining such measurements to special applications where accessible frame buffers already exist or elaborately equipped laboratories. We have developed a method which only requires storage of single TV lines or point scans. A digital oscilloscope captures these point scans and a laboratory microcomputer facilitates manipulation of the data to separate out different components of the noise power spectra. The x-ray dependent component of the noise power spectrum so produced is not the ordinary Wiener spectrum. However, it is shown that reconstruction of the full Wiener spectrum from this is possible subject only to the requirement that the x-ray noise spectrum at the output of the imaging system is circularly symmetric. PMID- 2308548 TI - An application of multivariate moment-generating functions to the analysis of signal and noise propagation in radiographic screen-film systems. AB - Previous studies [J. Opt. Soc. Am. 4A 895-901 (1987)] have shown the utility of multivariate moment-generating functions for analyzing the influence of stochastic amplifying and scattering mechanisms on the transfer of signal and noise through multistage imaging systems. Recently, these studies were extended to include cases in which the amplification or scattering parameters are themselves stochastic variables [J. Opt. Soc. Am. 6A, 1156-1164 (1989)]. In this paper we consider a special case in which amplification is followed by scattering such that the same random variable which characterizes the parameters of each amplification process also characterizes the parameters of the subsequent scattering of the amplified output events. In radiographic imaging, this can be used to describe the physics of the depth dependence of emission efficiency and light scatter in x-ray intensifying screens, which was originally treated by Lubberts [J. Opt. Soc. Am. 58, 1475-1483 (1968]). In this work Lubberts' original results are rederived in a more general form. They are then illustrated in terms of a diffusion model [Appl. Opt. 12, 1865-1870 (1973)] for light scatter within the intensifying screen. PMID- 2308550 TI - Determination of primary dose in 60Co gamma beam using a small attenuator. AB - A measurement technique previously proposed for determining dose from primary radiation has been tested using 60Co gamma rays. It is shown that the dose from primary radiation is reliably determined for field sizes of 10 X 10 and 20 X 20 cm2 at depths of 0.5, 5, and 10 cm in water. With further development this technique may be useful for verifying dose from primary radiation that may be calculated using a variety of methods. PMID- 2308549 TI - Validity of microsphere model in cerebral blood flow measurement using N isopropyl-p-(I-123) iodoamphetamine. AB - A microsphere model is sometimes used when calculating cerebral blood flow (CBF) using N-isopropyl-p-[I-123]iodoamphetamine (IMP), and is based on the assumption that there is essentially no washout of IMP. The validity of a microsphere model was investigated by comparison with the values of CBF obtained by means of a model which takes into consideration the diffusion of IMP from brain tissue to blood (nonmicrosphere model). When calculating CBF by the latter model, the look up table method was used with expression of the double integral in the model equation by the recursion relations, a method which is useful for obtaining pixel by-pixel values. The average rate constants for diffusion from brain to blood of gray and white matter were 0.021 and 0.0016 min-1, respectively. The values of CBF obtained by applying a microsphere model to the data acquired from 0 to 3.2 min after IMP injection were overestimated by approximately 23% compared with those values obtained using a nonmicrosphere model. This is considered to be due to the effect of the IMP activity in the vascular space. Values obtained using the data acquired from 3.2 to 6.4 min were underestimated by approximately 15%. When the values of CBF obtained by a microsphere model were interpolated, they became nearly equal to those obtained using a nonmicrosphere model at about 4 to 5 min after injection. This is suggested to be the reason why the underestimation due to diffusion from brain to blood is cancelled out by the overestimation due to the IMP in the vascular space. Our preliminary results suggest that it is necessary to take the diffusion of IMP from brain tissue to blood into account for the quantification of CBF using IMP. PMID- 2308551 TI - Testing of a medical linear accelerator's computer-control system. AB - In August of 1987, the Radiation Oncology Center at the Mallinckrodt Institute of Radiology became the first academic-medical-center user of Varian's computer controlled therapy accelerator, a prototype version of the 2100C. Installation was accomplished by the retrofit of a computer system to our two-year-old Clinac 1800. Being well aware of the malfunctions that occurred in other computer controlled accelerators, we took extraordinary measures to assure proper operation of the new, computerized, system. Our acceptance procedure included tests of (i) mechanical systems (isocentricity, digital readouts, etc.); (ii) radiation parameters (flatness, symmetry, output, etc.); (iii) manual safety systems (emergency off switches, etc.); (iv) the computer console systems (communications integrity, state integrity, etc.); and (v) the interlock systems (some 50 electrical, mechanical, and/or computer-controlled interlocks). As items (i), (ii), and (iii) do not differ significantly from the tests for a non computer-controlled machine, they will not be discussed here. Rather, this report will concentrate on the methods that were devised to test the computer-control and interlock systems. PMID- 2308552 TI - An advocate for Minnesotans' health. Interview by Richard L. Reece. PMID- 2308553 TI - A human services advocate. Interview by Richard L. Reece. PMID- 2308554 TI - Cost shifting and the uninsured. Symptom cured, malady worsens. PMID- 2308555 TI - Physician executives. Can they manage both worlds? PMID- 2308556 TI - Where to go for management training. PMID- 2308557 TI - Drinking water contaminants. Sources, health considerations, and removal. PMID- 2308558 TI - State health plan concerns patients, physicians. PMID- 2308559 TI - Medical Assistance reimbursement. An MMA legislative priority for 1990. PMID- 2308560 TI - Admission to the neonatal intensive care unit: reducing the risks. PMID- 2308561 TI - Evaluation of a multidisciplinary perinatal bereavement program. PMID- 2308562 TI - Use of live video transmission in the NICU. PMID- 2308564 TI - The very low-birthweight infant as an early social partner: exploring maternal reactions, expectations, and attitudes. PMID- 2308563 TI - The Plains Indians: cultural considerations in the use of apnea monitors. PMID- 2308565 TI - Values: directional signals for life choices. PMID- 2308566 TI - Vitamin E (alpha-tocopherol). PMID- 2308567 TI - Candidiasis in the premature infant. PMID- 2308568 TI - Medicine and technology. PMID- 2308569 TI - Just compensation. AB - The old saying about the squeaky wheel is true in politics. If physicians are not heard from, our share of the reimbursements will certainly be diminished or cut out. PMID- 2308570 TI - Battling illiteracy: each one, teach one. PMID- 2308571 TI - Pneumocystis carinii pneumonia: advances in diagnosis and therapy. AB - As the AIDS epidemic has evolved, so have improvements been made in diagnosis and treatment of Pneumocystis carinii pneumonia, the most common opportunistic infection in AIDS. Advances, changes, and current research are discussed. PMID- 2308572 TI - Hyperthermia treatment of brain tumors. AB - Hyperthermia is a promising new therapy for malignant glioma, a brain tumor with grim prognosis. The authors describe their work with hyperthermia delivered directly to tumor tissue via heating catheters. PMID- 2308573 TI - Angioplasty of persistent "stump" of internal carotid artery. AB - An unusual sequela of internal carotid artery occlusion is the development of cerebral ischemia caused by emboli in a residual stump of the internal carotid artery. Five patients with transient ischemic attacks due to this condition are presented. Stump angioplasty was employed successfully in each case. PMID- 2308574 TI - Risks of viral transmission by blood products: current status of preventive measures. AB - Patients are likely to ask their physicians about the safety of blood transfusions in the present era of AIDS fear. The authors address these concerns and discuss the risks of acquiring viral disease from a transfusion. PMID- 2308575 TI - Reflections on an old man, moods, life and death. PMID- 2308576 TI - Influenza vaccination coverage levels in selected sites--United States, 1989. PMID- 2308577 TI - Effect of platelet-activating factor (PAF) on sodium calcium exchange in cardiac sarcolemmal vesicles. AB - The effects of platelet-activating factor (PAF) on Na(+)-dependent calcium uptake in myocardial sarcolemmal vesicles were examined in order to clarify its mechanism of inotropic action on the heart. PAF (40 and 20 microM) significantly inhibited Na(+)-Ca2+ exchange by 61% and 37%, respectively. Both initial rate of exchange and maximal exchange were inhibited. The Km for the reaction was not altered but Vmax was lowered 55% by PAF. Lyso-PAF inhibited Na(+)-Ca2+ exchange to a similar degree as PAF. CV-3988, a specific PAF receptor antagonist, failed to diminish the inhibitory effect of PAF on Na(+)-Ca2+ exchange, suggesting that the effect of PAF on Na(+)-Ca2+ exchange is not via a receptor mechanism. The passive permeability of sarcolemmal vesicles to Ca2+ was markedly elevated after PAF treatment. However, this effect could not account for the decrease in Na(+) Ca2+ exchange. Interestingly, passive Ca2+ binding to cardiac sarcolemma was increased by 40 microM PAF. This study indicates that a depression of Na(+)-Ca2+ exchange probably does not play a role in the negative inotropic effect of PAF on the myocardium under physiological conditions. Its mechanism of action on Na(+) Ca2+ exchange is discussed. PMID- 2308578 TI - The characteristics of purified HL60 tuftsin receptors. AB - The purification and characteristics of purified HL60 tuftsin receptors are described. Purification was accomplished by affinity chromatography similar to that described earlier, wherein a tuftsin analog Thr-Lys-Pro-Pro-Arg, is covalently linked at the N alpha group to a solid support. The receptor consists presumably of two subunits approximately 66 KDa and 57 KDa. The dissociation constant of the receptor complex is 4.7 X 10(-8) M with 5 X 10(4) receptors per cell. It can form oligomers with an Mr of about 560 KDa suggesting an octomeric structure, assuming the same number of each subunit is associated. PMID- 2308579 TI - Organic cations substituted for sodium are toxic to cultured rat glioma cells. AB - As a prelude to studying the sodium dependence of choline-transport systems, a number of organic compounds plus LiCl, CsCl and RbCl as sodium substitutes were tested for toxicity to maintain isoosmolality or ionic strength on cultured rat astrocytoma cells. In short term experiments (1 hour), tetramethylammonium chloride, triethanolammonium chloride, guanidinium chloride, tris hydrochloride, mannitol, sucrose, LiCl, RbCl and CsCl were well tolerated. In long term exposure (4 days), no compound was completely nontoxic as a sodium substitute, but sucrose, mannitol, LiCl, and RbCl allowed maximum cell survival. PMID- 2308580 TI - Modulation of adenylate cyclase activity by Ca2+, phospholipid-dependent protein kinase in rat brain striatum. AB - The effects of purified Ca2+, phospholipid-dependent protein kinase (C-kinase) were studied on adenylate cyclase activity from rat brain striatum. C-kinase treatment of the membranes stimulated adenylate cyclase activity, the maximal stimulation between 50-80% was observed at 3.5 U/ml, whereas the catalytic subunit of cAMP dependent protein kinase did not show any effect on enzyme activity. The inclusion of Ca2+ and phosphatidyl serine did not augment the percent stimulation of adenylate cyclase by C-kinase, however EGTA inhibited the stimulatory effect of C-kinase on enzyme activity. Furthermore, the known inhibitors of C-kinase such as polymyxin-B and 1-(5-Isoquinoline sulfonyl)-2 methylpiperazine dihydrochloride (H-7) also inhibited the stimulatory effect of C kinase on adenylate cyclase activity. In addition, in the presence of GTP the stimulatory effects of C-kinase on basal and N-Ethylcarboxamide adenosine- (NECA ), dopamine-(DA) and forskolin- (FSK) sensitive adenylate cyclase activities were augmented. On the other hand, the inhibitory effect of high concentrations of GTP on enzyme activity was attenuated by C-kinase treatment. In addition, oxotremorine inhibited adenylate cyclase activity in a concentration dependent manner, with an apparent Ki of about 10 microM and C-kinase treatment almost completely abolished this inhibition. These data suggest that C-kinase may play an important role in the regulation of adenylate cyclase activity possibly by interacting with a guanine nucleotide regulatory protein. PMID- 2308581 TI - Short DNA fragments induce site specific recombination in mammalian cells. AB - A defective hprt gene was corrected by homologous recombination in a lymphocyte cell line deficient in Hypoxanthine-phosphoribosyl-transferase activity (hprt). In a novel approach, only a fragment of a cDNA clone of the functional hprt gene was used to induce homologous recombination. The mutation that was corrected corresponds to a single base change in exon III of the hprt gene. Two transfection methods, electroporation and the previously unreported use of polyoma capsids containing only short DNA fragments, were able to induce the recombinational event. After transfection cells with a functional hprt gene were selected and homologous recombination events were identified using polymerase chain reaction. Double stranded fragments and both coding and non-coding single stranded fragments resulted in conversion to a functional gene. Analysis of the resulting hprt positive cells revealed that most cells had undergone a simple replacement reaction. Interestingly, however, some cells had lost an intron adjacent to the site of mutation. Potential mechanisms for this phenomenon, including the possible involvement of RNA in DNA repair, are discussed. PMID- 2308582 TI - Stimulation and inhibition of cardiac myocyte proliferation in vitro. AB - We have examined the effect of crude cardiac tissue extracts as well as that of several growth factors and triiodothyronin (T3) on DNA synthesis of cardiac myocytes in culture. Extracts from embryonic and adult cardiac tissue stimulated DNA synthesis of myocytes. Atrial myocytes exhibited overall higher degree of stimulation than their ventricular counterparts and extracts from adult atrial tissue had the highest apparent mitogenic activity for atrial myocytes. We have shown that adult heart contains basic fibroblast growth factor (bFGF), especially in the atria. Transforming growth factor beta (TGF beta) and insulin-like growth factors (IGFs) are also accumulated in cardiac tissues. We found that bFGF and the IGFs stimulate myocyte cell proliferation and DNA synthesis. These factors also stimulate cardiac non-muscle proliferation, especially in the presence of serum. TGF beta inhibited proliferation and DNA synthesis and cancelled the effect of bFGF or IGFs on the myocytes. T3 also diminished the bFGF-induced mitogenic stimulation of cardiomyocytes. Our data suggest that these factors may be involved in the regulation of cardiomyocyte proliferation in vivo. PMID- 2308583 TI - Studies on the effect of ketoconazole on the fusion of L6 myoblasts. AB - The effect of ketoconazole on the fusion of L6 myoblasts was studied. Ketoconazole was a potent inhibitor of myoblast fusion at concentrations as low as 0.1 microM, but fusion was restored when the inhibitor was removed. The inhibitor resulted in decreased binding of conA and WGA to cell surface oligosaccharides showing that it was inhibiting N-linked cell surface glycoproteins. Inhibition of fusion by ketoconazole was accompanied by reduced creatine phosphokinase activities showing that it is affecting biochemical differentiation. Incorporation of labelled mannose from GDP-mannose into lipid sugar and lipid-oligosaccharide complexes involved in the synthesis of N-linked oligosaccharides was also inhibited by ketoconazole, but the inhibition was reversed by addition of exogenous dolichol phosphate to the incorporation mixture. The main conclusion from these studies was that ketoconazole inhibited fusion of L6 myoblasts by affecting the synthesis of dolichol-phosphate required for the synthesis of lipid-oligosaccharides needed for the synthesis of fusogenic cell surface N-linked glycoproteins. PMID- 2308584 TI - [Unity of diagnostic pathology, continuing education and research at our institute]. AB - Authors give a brief view on the activity in Institute of Pathology and Histopathology of Post-graduate University of Medicine. In its frame, close relation of diagnostic, post-graduate education and research activity is illustrated by examples of different fields (intestinal, cardiac, vascular system, respiratory tract, organ of locomotion, urological diseases, electronmicroscopic tumor diagnostics, endocrinology). Importance of modern morphological methods and their place both in practical and scientific activity are dealt with. PMID- 2308585 TI - [Malignant lymphomas: pathomorphology and experiment]. AB - The last fifteen years have provided a significant development in pathomorphological diagnosis of malignant lymphomas (ml), in clinical fellow-up of patients and in its therapy. Diagnosis is built on functional morphological basis (immunohistology). New methods have reslited in identification of new types of mls. On the basis of high number of cases registered in Lymphoma Reference Centre, specific organic distribution new entities can be determined. Perifollicular B-cellular mls of MALT type are frequent in gastrointestinal tract and are rare in Waldeyer ring and in lymph nodes. Flow cytometric determination of DNA content of cells proved to be very useful in diagnostics of mls, so the probably determination of aneuploid and proliferative activity, respectively. These parameters are of prognostic significance. Recirculation of lymphocytes may play a role in dissemination os nHmls. It can be studied in immunomorphological (in vitro) test ased on the interaction (adherence) of lymphocytes and of endothelial cells of high endothelial postcapillary venule. Our observations present that B-cellular CLL and clonal cells of plasma cellular leukemia show endothelial adherence, while multiple cells of myeloma do not. PMID- 2308586 TI - [Morphology of cardiac myxomas]. AB - Author describes her experiences gained by light microscopic, immunohistochemical and electronmicroscopic studies of 11 cardiac myxomas. New data on debated histogenesis of myxomas were tried to be gained by her studies. A part of myxoma cells was poor in organelles ultrastructurally, mostly settled by one, in the other part more organelles and intra-cytoplasmatic filaments could be detected, majority of them was of process. Glandular structures, showing mucous production, were in a tumor. Majority of tumor cells showed vimentin immunoreactive by immunohistochemical studies. In addition, lysozyme immunoreactive cells could also be observed; 8th factor associated antigen, however, could be detected in glandular structures. On basis of studies, the assumption seems to be probably, according to which the cardiac myxomas originate from embryonal cells, capable to endodermal and mesodermal cytogenesis. PMID- 2308587 TI - [The damaged environment. Heart and lung changes]. AB - Author evaluates cardiac and pulmonary changes developed by environmental pollution, from the point of view of forensic expert. The myocardium and parenchyma are the target organs of multicasual damages. Attention is called to the role of forensic expert in prevention of environmental damages and in the evaluation of the effects. PMID- 2308588 TI - [Variabilities of kinetics of alcohol catabolism]. AB - The resorption, distribution and elimination of ethanol vary individually. The differences in the resorption deficit and elimination coefficient can be of great extent. Though the generally accepted average of resorption deficit is 20%, which is calculated with in forensic practice, this value can occasionally be a lot higher. The elimination coefficient (beta value) depends on the blood alcohol level. Beta value was found higher than 0.15%o/h, the generally accepted one, even below 1.5% blood alcohol content, above 2.5% the beta value was found to be as high as 0.33%o h. This faster rate of ethanol clearance is due to induction of alcohol elimination systems. The ethanol metabolism at higher blood alcohol levels is characterized by Michaelis-Menten kinetics. PMID- 2308589 TI - Biochemical and cytogenetical characterization of Chinese hamster ovary X-ray sensitive mutant cells xrs 5 and xrs 6. VI. The correlation between UV-induced DNA lesions and chromosomal aberrations, and their modulations with inhibitors of DNA repair synthesis. AB - The role of UV-induced DNA lesions and their repair in the formation of chromosomal aberrations in the xrs mutant cell lines xrs 5 and xrs 6 and their wild-type counterpart, CHO-K1 cells, were studied. The extent of induction of DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) due to UV irradiation in the presence or absence of 1-beta-D-arabinofuranosylcytosine (ara C) and hydroxyurea (HU) was determined using the alkaline and neutral elution methods. Results of these experiments were compared with the frequencies of induced chromosomal aberrations in UV-irradiated G1 cells treated under similar conditions. Xrs 6 cells showed a defect in their ability to perform the incision step of nucleotide repair after UV irradiation. Accumulation of breaks 2 h after UV irradiation in xrs 6 cells in the presence of HU and ara-C remained at the level of incision breaks estimated after 20 min, which was about 35% of that found in wild-type CHO-K1 cells. In UV-irradiated CHO-K1 and xrs 5 cells, more incision breaks were present after 2 h compared with 20 min post-treatment with ara-C, a further increase was evident when HU was added to the combined treatment. The level of incision breaks induced under these conditions in xrs 5 was about 80% of that observed in CHO-K1 cells. UV irradiation itself did not induce any detectable DNA strand breaks. Accumulation of SSBs in UV-irradiated cells post-treated with ara-C and HU coincides with the increase in the frequency of chromosomal aberrations. These data suggest that accumulated SSBs when converted to DSBs in G1 give rise to chromosome-type aberrations, whereas strand breaks persisting until S-phase result in chromatid-type aberrations. Xrs 6 appeared to be the first ionizing-radiation-sensitive mutant with a partial defect in the incision step of DNA repair of UV-induced damage. PMID- 2308590 TI - Differential cell cycle modulation of human DNA glycosylases against oxidized pyrimidines. AB - Cellular DNA is continuously subject to damages by both endogenous and exogenous oxidizing agents. Excision repair of oxidized bases in human cells is initiated by DNA glycosylases which remove them from DNA. 5-Hydroxymethyluracil-DNA glycosylase excises 5-hydroxymethyluracil from DNA. A different enzyme, termed a redoxyendonuclease, has glycosylase activity against many modified DNA pyrimidines. The regulation of these enzymes in proliferating human cells was examined. Both glycosylases were assayed in serum-stimulated WI-38 cells by measurements of direct release of modified free bases from their respective DNA substrates. There was no significant variation of 5-hydroxymethyluracil-DNA glycosylase activity during the cell cycle. However, the glycosylic activity of the redoxyendonuclease was stimulated with DNA synthesis. This activity again increased at the beginning of a second cell cycle. Therefore, the glycosylases that initiate excision repair of oxidized DNA are subject to different controls during the cell cycle. PMID- 2308591 TI - Evidence to support the existence of efficient DNA double-strand break rejoining in a radiosensitive mutant of V79-4 following irradiation with 250 kVp X-rays or neutrons. AB - The repair of ionising-radiation-induced DNA double-strand break type damage was measured by Kohn neutral elution in an X-ray-sensitive mutant of V79-4, irs1. This was done in order to investigate further the likelihood that irs1 carries a defect which leads to error-prone repair of DNA damage, and not simply a reduced ability to rejoin DNA double-strand breaks. The mutant displayed an equal increase in sensitivity to the lethal effects of neutrons, as compared to X-rays. Both irs1 and V79-4 showed an increased sensitivity to the killing effects of neutrons of around 2 at 10% survival. irs1 also showed an exponential survival after either X-rays or neutrons. The induction of DNA double-strand breaks was measured in both cell lines over a dose range of 10-40 Gy using Kohn neutral filter elution. Induction of breaks by X-rays in irs1 seemed to increase slightly with dose, relative to induction in V79-4, so that at 40 Gy 1.5 times more DNA double-strand breaks were measured in irs1 cells than in V79-4. Neutron irradiation resulted in a more similar level of induction in either strain after 10-40 Gy. This difference in induction of damage may be due to a different cell cycle composition in either cell line. The rejoining of X-ray induced double strand breaks showed a very similar pattern (on a percentage rejoined basis) in both cell lines, although from the induction data at 40 Gy, the dose at which rejoining was measured, fewer breaks were rejoined in V79-4 but also fewer breaks remained unsealed. Neutron-induced breaks, however, were rejoined more efficiently in irs1 again on a percentage basis, but also in absolute terms since similar induction was seen after 40 Gy. This data, together with the differences seen in the rejoining of X-ray compared to neutron induced breaks, may indirectly support the proposal that irs1 is a misrepair mutant. PMID- 2308592 TI - DNA-break repair, radioresistance of DNA synthesis, and camptothecin sensitivity in the radiation-sensitive irs mutants: comparisons to ataxia-telangiectasia cells. AB - Induction and rejoining of DNA single-strand breaks (ssb) and double-strand breaks (dsb) after gamma-irradiation were measured, respectively, by alkaline and neutral sucrose gradient sedimentation methods. The radiosensitive mutants irs1, irs2, and irs3 showed no significant difference from wild-type V79 hamster cells in ability to rejoin either ssb or dsb, while the previously-described xrs-1 mutant showed the expected defect in rejoining dsb. The resistance of DNA synthesis to gamma-irradiation was measured in the 3 irs mutants and, for comparative purposes, in transformed human cell lines from normal and ataxia telangiectasia (A-T) individuals. The irs2 mutant was found to be very similar in response to the A-T lines, showing a marked decrease in inhibition of DNA synthesis, compared to V79 cells, in both time-course and dose-response experiments. However, irs1 also had some decrease in inhibition at the higher doses used, while irs3 was similar to the wild-type V79 cells. Both irs1 and irs2 were found to be considerably more sensitive to the DNA topoisomerase I-inhibitor camptothecin, while irs3 was only slightly more sensitive than the parent V79 line. These data place the irs mutants in a similar category of radiosensitive phenotype to A-T cells, but we view this as only the beginning of a useful classification of this type of mutant. The irs2 mutant has the strongest links to A-T cells, through its sensitivity profile to DNA-damaging agents and radioresistant DNA synthesis, but irs1 in particular has other similarities to A T. PMID- 2308593 TI - Chromatin-associated DNA endonucleases from xeroderma pigmentosum cells are defective in interaction with damaged nucleosomal DNA. AB - The influence of nucleosome structure on the activity of 2 chromatin-associated DNA endonucleases, pIs 4.6 and 7.6, from normal human and xeroderma pigmentosum, complementation group A (XPA), lymphoblastoid cells was examined on DNA containing either psoralen monoadducts or cross-links. As substrate a reconstituted nucleosomal system was utilized consisting of a plasmid DNA and either core (H2A, H2B, H3, H4), or total (core plus H1) histones from normal or XPA cells. Both non-nucleosomal and nucleosomal DNA were treated with 8 methoxypsoralen (8-MOP) plus long-wavelength ultraviolet radiation (UVA), which produces monoadducts and DNA interstrand cross-links, and angelicin plus UVA, which produces monoadducts. Both normal endonucleases were over 2-fold more active on both types of psoralen-plus-UVA-damaged core nucleosomal DNA than on damaged non-nucleosomal DNA. Addition of histone H1 to the system reduced but did not abolish this increase. By contrast, neither XPA endonuclease showed any increase on psoralen-treated nucleosomal DNA, with or without histone H1. Mixing the normal with the XPA endonucleases led to complementation of the XPA defect. These results indicate that interaction of these endonucleases with chromatin is of critical importance and that it is at this level that a defect exists in XPA endonucleases. PMID- 2308594 TI - Unscheduled DNA synthesis after treatment with 20-methylcholanthrene and N nitrosodimethylamine in primary culture of human gallbladder epithelial cells. AB - Unscheduled DNA synthesis (UDS) induced by treatment with 20-methylcholanthrene (MCA) and N-nitrosodimethylamine (DMN) was measured in cultured human gallbladder epithelial cells. MCA induced UDS very efficiently, while DMN was far less effective than MCA. Addition of rat S9 mixture did not affect the amount of UDS by the chemicals. Differences between the present results in human cells and our previous findings in bovine cells could be due to species and tissue specificity. PMID- 2308595 TI - Differential poly(ADP-ribose) metabolism in repair-proficient and repair deficient murine lymphoma cells. AB - The UV254nm-sensitive, tumorigenic murine lymphoma cell line LY-R undergoes spontaneous conversion into a UV254nm-resistant, non-tumorigenic LY-S subline after prolonged culture in vitro. Here we describe that this conversion leads to distinct changes in several features of intranuclear ADP-ribose polymer metabolism, which may contribute to the altered processing of DNA damage in these cells. The UV254nm-resistant LY-S cells contain 3-fold higher levels of ADP ribose polymers than LY-R cells. The initial catabolic rate of degradation of these polymers is more than 6-fold higher in LY-S cells. UV254nm irradiation raises the catabolic rates of ADP-ribose polymers in both cell lines. As a consequence, the polymer half-lives decrease from 15 min to 4 min in LY-S cells, and from 96 min to 19 min in LY-R cells. In addition, the rapidly turning over fraction of polymers is much larger in the UV254nm-resistant LY-S cells. These data suggest that the catabolism of poly(ADP-ribose) may be an important factor in the biological expression of DNA damage. PMID- 2308596 TI - Clastogenic effects of cis-diamminedichloroplatinum. II. Induction of chromosomal aberrations in primary spermatocytes and spermatogonial stem cells of mice. AB - The clastogenic effect of the anticancer drug cis-diamminedichloroplatinum (II) (cisplatin) on meiotic prophase in primary spermatocytes and on spermatogonial stem cells of male (101/E1 x C3H/E1)F1 mice was studied. The intraperitoneal doses of cisplatin tested were 5.0, 7.5 and 10.0 mg/kg. Chromosomal aberrations were examined at diakinesis-metaphase 1 of meiosis 1-13 days after treatment, representing cells treated at diplotene, pachytene, zygotene, leptotene an preleptotene. Reciprocal translocations were evaluated 63-70 days after treatment, representing treated stem-cell spermatogonia. Cisplatin had a toxic effect in zygotene to preleptotene of meiosis, as indicated by the significant reduction in testicular weight. At diplotene, pachytene and zygotene no enhancement of aberrations was found. An increase in aberrant cells was observed during leptotene with preleptotene being the most sensitive stage. The dose response relationship for aberrant cells was linear on day 13 after treatment. It is concluded that, like mitomycin C (Adler, 1976), cisplatin primarily caused aberrations during the premeiotic phase of DNA synthesis. No significant increase of translocation multivalents was found after treatment of stem-cell spermatogonia. PMID- 2308597 TI - DNA repair and chromosomal stability in the alkylating agent-hypersensitive Chinese hamster cell line 27-1. AB - 27-1 is a mutant of Chinese hamster ovary cells (CHO cells) that is hypersensitive to the toxic effects of ultraviolet light, N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and other monofunctional alkylating agents. We show here that the enhanced MNNG sensitivity of these cells is not due to alterations in the amount of DNA methylation products introduced nor by a defect in the first step of removal of the main alkylation products 7-methylguanine and 3 methyladenine. However, these mutant cells perform more DNA repair synthesis after treatment with MNNG than normal CHO-9 cells. This observation might indicate a possible defect of a ligase involved in sealing DNA repair patches. 27 1 cells did not show elevated frequencies of sister-chromatid exchange and chromosomal aberration induced by MNNG. The data show that MNNG-induced cell killing is not necessarily related to increased chromosomal instability. PMID- 2308598 TI - The effect of glutathione depletion on sister-chromatid exchange induction by cytostatic drugs. AB - Using sister-chromatid exchanges (SCEs) as an indicator for DNA damage, we investigated the role of glutathione (GSH) as a determinant of cellular sensitivity to the DNA-damaging effects of the cytostatic drugs adriamycin (AM) and cyclophosphamide (CP). Exposure of V79 cells to buthionine sulfoximine (BSO) resulted in a complete depletion of cellular GSH content without toxicity and without increasing the SCE frequency. Subsequent 3-h treatment of GSH-depleted cells with AM or S9-mix-activated CP caused a potentiation of SCE induction. In Chinese hamster ovary (CHO) cells, which showed a higher GSH level compared to V79 cells, BSO treatment led to a depletion of GSH to about 5% of the control and increased SCE induction by AM and CP. Compared to V79 cells, the effect of AM on SCE frequencies was less distinct in CHO cells, while CP exerted a similar effect in both cell lines. Pretreatment of V79 cells with GSH increased the cellular GSH content, but had no effect on the induction of SCEs by AM, and pretreatment with cysteine influenced neither GSH levels nor SCE induction by AM. The study shows that SCEs are a suitable indicator for testing the modulation of of drug genotoxicity by GSH. The importance of different GSH contents of cell lines for their response to mutagens is discussed. PMID- 2308599 TI - Thymidylate synthetase gene as a quantitative mutation marker in Chinese hamster cells. AB - A quantitative mutation marker for cultured mammalian cells is presented which uses a selective medium containing folinic acid, aminopterin and thymidine (the 'FAT' medium) to select for mutants deficient in thymidylate synthetase (TS) activity. Optimization of FAT medium was carried out using Chinese hamster V79 cell lines having 3 levels of TS activity. By manipulating the concentration of folinic acid in FAT medium, TS-deficient mutants can be readily selected. TS mutation is inducible in a dose-dependent manner by either ethyl methanesulfonate or ultraviolet light irradiation. Expression time for TS mutation was also determined using two concentrations of ethyl methanesulfonate and found to be very short, being 1 or 2 days. This newly characterized TS mutation marker should be useful in the study of both spontaneous and induced mutagenesis. PMID- 2308600 TI - Impaired function of macrophage Fc gamma receptors in end-stage renal disease. AB - Infection is a frequent complication in patients undergoing hemodialysis for end stage renal disease and is the primary cause of mortality among such patients. Macrophages are important in host defense against infection largely because their Fc gamma receptors recognize antibody-coated bacteria. We therefore studied macrophage Fc gamma-receptor function in vivo and in vitro in 56 patients with end-stage renal disease who were on hemodialysis and in 20 healthy volunteers. The clearance of IgG-coated (sensitized) autologous red cells was decreased in 53 patients. The inhibition of clearance in the 56 patients was 52 +/- 3 percent at 1 hour, 41 +/- 5 percent at 1 1/2 hours, and 29 +/- 5 percent at 2 hours (P less than 0.001). The clearance of unsensitized erythrocytes and heat-altered autologous erythrocytes was normal. The impairment of clearance was not correlated with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The recognition of these IgG-sensitized red cells in vitro by Fc gamma RI (an Fc gamma-receptor protein that binds monomeric IgG) on blood monocytes from the patients was also significantly decreased (P less than 0.001) but was partially improved by hemodialysis. Nine patients had severe infections during a two-year follow-up period. The clearance of IgG-coated cells in these patients (half-time, 12.9 +/- 1.7 hours) was significantly impaired, as compared with that in the 47 patients without severe infections (half-time, 4.4 +/- 1.8 hours; P less than 0.001). We conclude that macrophage Fc gamma-receptor function is impaired in patients with end-stage renal disease who are undergoing hemodialysis, and that this impairment probably contributes to the observed immunodepression and high prevalence of infection among such patients. PMID- 2308601 TI - Results of single-lung transplantation for bilateral pulmonary fibrosis. The Toronto Lung Transplant Group. AB - Between November 1983 and August 1989, we performed single-lung transplantation for end-stage pulmonary fibrosis in 20 patients. Nine patients (45 percent) who survived for more than one year form the basis of this report. Before surgery, the nine survivors had severe restrictive lung disease, with a mean (+/- SD) vital capacity (VC) of 43 +/- 9 percent, a forced expiratory volume in one second (FEV1) of 50 +/- 9 percent, and a single-breath diffusing capacity (DLCO) of 36 +/- 9 percent of predicted values. One year after transplantation, the patients' VC had reached 69 +/- 10 percent, FEV1 79 +/- 15 percent, and DLCO 62 +/- 16 percent of predicted values. Relative perfusion to the transplanted lung rose from 63 +/- 14 percent (three days after surgery) to 77 +/- 7 percent within three months and stayed constant or increased slightly thereafter. Before surgery, despite supplemental oxygen at flow rates varying from 1 to 9 liters per minute, none of the patients could exercise beyond stage 1/2 (2.7 km [1.7 miles] per hour, 5 percent grade) on a modified Bruce treadmill-exercise protocol. All eight patients tested one year or more after transplantation achieved at least stage 1 (2.7 km [1.7 miles] per hour, 10 percent grade), and usually a higher stage, without supplemental oxygen. Arterial oxygen tension returned to normal values in most patients (87 +/- 13 mm Hg), and supplemental oxygen, which all patients required before surgery, was no longer needed by any patient after transplantation. We conclude that in carefully selected patients with end-stage pulmonary fibrosis, single-lung transplantation is an effective treatment. PMID- 2308602 TI - Small-bowel length and the dose of cyclosporine in children after liver transplantation. AB - Children, particularly infants, require large oral doses of cyclosporine to achieve immunosuppression after liver transplantation. In 53 children who had received liver transplants, we examined the relation of height, weight, residual small-bowel length, and (in 17 children) the terminal plasma clearance rate of cyclosporine to the dose of cyclosporine required to achieve blood levels of 200 ng per milliliter. The required intravenous dose of cyclosporine (expressed as milligrams per day) increased steeply as body size and bowel length increased, whereas the required oral dose declined with increasing bowel length. When expressed as milligrams per square meter of body-surface area per day, the required intravenous dose did not change with body size, but the required oral dose declined with increasing body size. Small-bowel length correlated closely and inversely with the log of the oral dose of cyclosporine (r = -0.77, P = 0.0001). The rate of clearance was also related to the log of the oral dose (r = 0.57, P = 0.017) but was independent of age and size. Multiple regression analyses that included height and weight showed that only small-bowel length and the rate of clearance from plasma were independently related to the required oral dose of cyclosporine. We concluded that the length of the small bowel is the chief determinant of the required dose of orally administered cyclosporine in children after liver transplantation. Children and infants require large oral doses of cyclosporine because of the limited absorptive surface area of their intestines. PMID- 2308603 TI - Declining American representation in leading clinical-research journals. AB - To determine the national origins of high-quality clinical research we looked at research articles published during the past decade in three leading general clinical-research journals, the New England Journal of Medicine, the Journal of Clinical Investigation, and the Lancet, and in a specialty journal, Blood. We found that the proportion of non-U.S. papers published annually in these journals increased between two- and almost threefold, irrespective of whether the total number published per year rose (the Journal of Clinical Investigation and Blood), fell (the Lancet), or remained constant (the New England Journal of Medicine). Most non-U.S. research published in these periodicals originated in Western Europe or Japan. The limited available data on papers sent to the journals revealed a decline in the number of U.S. papers submitted in recent years (the New England Journal of Medicine) or a slower rate of increase relative to that of non-U.S. submissions (Blood), indicating that the increase in the number of non U.S. papers published reflects an increase in the amount of high-quality research originating abroad as compared with the amount originating in the United States. The explanation for this phenomenon is unclear, but it coincides with the slowed growth of funding from the National Institutes of Health for U.S. clinical research. PMID- 2308604 TI - Uremia and host defenses. PMID- 2308605 TI - Lung transplantation comes of age. PMID- 2308606 TI - Sex, lies, and HIV. PMID- 2308607 TI - Transfusion-associated HIV infection. PMID- 2308608 TI - Use of anabolic-androgenic steroids by athletes. PMID- 2308609 TI - Should Jehovah's Witnesses be denied intensive chemotherapy for acute leukemia? PMID- 2308610 TI - Treatment of benign essential blepharospasm with cyproheptadine. PMID- 2308611 TI - Unusual esophageal obstruction. PMID- 2308612 TI - Centrifugal forces on the medical profession. PMID- 2308613 TI - The alpha and beta errors in randomized trials. PMID- 2308614 TI - The new academic medical center. PMID- 2308615 TI - Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. AB - Recent neuroradiologic and neuropathological studies indicate that at least some patients with schizophrenia have slightly enlarged cerebral ventricles and subtle anatomical abnormalities in the region of the anterior hippocampus. Using magnetic resonance imaging (MRI), we studied 15 sets of monozygotic twins who were discordant for schizophrenia (age range, 25 to 44 years; 8 male and 7 female pairs). For each pair of twins, T1-weighted contiguous coronal sections (5 mm thick) were compared blindly, and quantitative measurements of brain structures were made with a computerized image-analysis system. In 12 of the 15 discordant pairs, the twin with schizophrenia was identified by visual inspection of cerebrospinal fluid spaces. In two pairs no difference could be discerned visually, and in one the twin with schizophrenia was misidentified. Quantitative analysis of sections through the level of the pes hippocampi showed the hippocampus to be smaller on the left in 14 of the 15 affected twins, as compared with their normal twins, and smaller on the right in 13 affected twins (both P less than 0.001). In the twins with schizophrenia, as compared with their normal twins, the lateral ventricles were larger on the left in 14 (P less than 0.003) and on the right in 13 (P less than 0.001). The third ventricle also was larger in 13 of the twins with schizophrenia (P less than 0.001). None of these differences were found in seven sets of monozygotic twins without schizophrenia who were studied similarly as controls. We conclude that subtle abnormalities of cerebral anatomy (namely, small anterior hippocampi and enlarged lateral and third ventricles) are consistent neuropathologic features of schizophrenia and that their cause is at least in part not genetic. Further study is required to determine whether these changes are primary or secondary to the disease. PMID- 2308616 TI - Sexual behavior of college women in 1975, 1986, and 1989. AB - To compare sexual practices in college women before and after the start of the current epidemics of Chlamydia trachomatis, genital herpesvirus, and human immunodeficiency virus type 1 infection, we surveyed 486 college women who consulted gynecologists at a student health service in 1975, 161 in 1986, and 132 in 1989 at the same university. There were no statistically significant differences in age, age at menarche, or reason for visiting the gynecologist. The percentages of women in this population who were sexually experienced were the same in all three years (88 percent in 1975, 87 percent in 1986, and 87 percent in 1989). Oral contraceptives were used by 55 percent of the women in 1975, 34 percent in 1986, and 42 percent in 1989; the use of condoms as the usual method of birth control increased (6 percent in 1975, 14 percent in 1986, and 25 percent in 1989; P less than 0.001). In 1975, only 12 percent reported the regular use of condoms during sexual intercourse, in some cases in conjunction with other methods of contraception, as compared with 21 percent in 1986 and 41 percent in 1989 (P = 0.0014). No significant differences were found in the three surveys in the number of male sexual partners or the frequency of fellatio, cunnilingus, or anal intercourse. An additional sample of 189 college women who did not consult the health service was surveyed in 1989, and similar sexual behavior was reported by those who were sexually experienced (65 percent). We conclude that in this population there has been little change in sexual practices in response to new and serious epidemics of sexually transmitted diseases, with the exception of an increase in the use of condoms (which still does not reach 50 percent). PMID- 2308617 TI - Schizophrenia and the brain. PMID- 2308618 TI - Fluoride and bone--quantity versus quality. PMID- 2308619 TI - Licorice, tobacco chewing, and hypertension. PMID- 2308620 TI - Matching for age in renal transplantation. PMID- 2308621 TI - Secondary cancers after bone marrow transplantation. PMID- 2308622 TI - Locus for susceptibility to melanoma on chromosome 1p. PMID- 2308623 TI - Growth hormone-receptor gene in Laron dwarfism. PMID- 2308624 TI - Repeated type E botulism in an Alaskan Eskimo. PMID- 2308625 TI - Treatment of an impacted fecalith with electrohydraulic lithotripsy. PMID- 2308626 TI - MRI--a patient's perspective. PMID- 2308627 TI - Pathobiology training for basic scientists. PMID- 2308628 TI - Gene targeting: tapping the cellular telephone. PMID- 2308629 TI - Ecology: stability from variability. PMID- 2308630 TI - SIV grows unchanged in human cells. PMID- 2308631 TI - Evolution of tetrapod hearing. PMID- 2308632 TI - Transparency and coherence in human motion perception. AB - When confronted with moving images, the visual system often must decide whether the motion signals arise from a single object or from multiple objects. A special case of this problem arises when two independently moving gratings are superimposed. The gratings tend to cohere and move unambiguously in a single direction (pattern motion) instead of moving independently (component motion). Here we report that the tendency to see pattern motion depends very strongly on the luminance of the intersections (that is, to regions where the gratings overlap) relative to that of the gratings in a way that closely parallels the physics of transparency. When the luminance of these regions is chosen appropriately, pattern motion is destroyed and replaced by the appearance of two transparent gratings moving independently. The observations imply that motion detecting mechanisms in the visual system must have access to tacit 'knowledge' of the physics of transparency and that this knowledge can be used to segment the scene into different objects. The same knowledge could, in principle, be used to avoid confusing shadows with real object boundaries. PMID- 2308633 TI - Neuropeptide fusion of two motor-pattern generator circuits. AB - Animals make many different movements as circumstances dictate. These movements often involve the coordination of several neural networks, the output of which can be changed by modulatory substances. Here we report that the neuropeptide red pigment concentrating hormone modulates the interactions between two rhythmic pattern-generating networks in the lobster stomatogastric nervous system. Red pigment concentrating hormone markedly enhances the amplitude of synaptic interactions between elements of two pattern-generating networks--the cardiac sac and the gastric mill. Consequently, two networks operating under some circumstances virtually independently can be fused into one functional unit operating differently from either of the two original networks. These results show how a neuropeptide can alter the functional configuration of a neural network so that widely disparate outputs can be produced by the same neurons. PMID- 2308634 TI - Self-tolerance to transgenic gamma delta T cells by intrathymic inactivation. AB - During their intrathymic differentiation, T lymphocytes expressing alpha beta T cell receptors (TCR) are negatively and positively selected. This selection contributes to the establishment of self-tolerance and ensures that mature CD4+ and CD8+ cell populations are restricted by the self major histocompatibility complex. Little is known, however, about gamma delta T-cell development. To investigate whether selection operates in the establishment of the gamma delta T cell class, we have generated transgenic mice using gamma- and delta-transgenes encoding a TCR that is specific for a product of a gene in the TL-region of the TLb haplotype. Similar numbers of thymocytes expressing the transgenic TCR were generated in mice of TLb and TLd haplotypes. But gamma delta thymocytes from TLb and TLd transgenic mice differed in cell size, TCR density and in their capacity to respond to TLb stimulator cells or interleukin-2 (IL-2). In contrast to gamma delta T cells from TLd transgenic mice, gamma delta T cells from TLb transgenic mice did not produce IL-2 and did not proliferate in response to TLb stimulator cells, but they did proliferate in the presence of exogenous IL-2. These results indicate that functional inactivation of self-antigen-specific T cells could contribute to the establishment of self-tolerance to thymic determinants. PMID- 2308635 TI - Gene targeting in normal and amplified cell lines. AB - Targeted recombination in mammalian cells is rare compared with non-homologous integration. In Saccharomyces cerevisiae the reverse is true. Differences in targeting efficiency could arise because a target of unique DNA is 200 times more dilute in mammalian genomes than it is in yeast. We tested this possibility by measuring gene targeting in normal CHO cells with two copies of the dihydrofolate reductase (DHFR) gene and in amplified CHOC 400 cells, which carry 800 copies. If the concentration of the target gene is critical, amplified cells should show an enhanced frequency of targeted recombination relative to non-homologous integration. Using a positive/negative selection protocol, we demonstrated that the efficiency of targeting into DHFR genes is indistinguishable in normal and amplified CHO cells. As targeting does not depend on the number of targets, the search for homology is not a rate-limiting step in the mammalian pathway of gene targeting. Thus, the difference in genome size is not the basis for the different outcomes of targeting experiments in S. cerevisiae and mammals. PMID- 2308636 TI - Dependence of the torsional rigidity of DNA on base composition. AB - The Escherichia coli phage 434 repressor binds as a dimer to the operator of the DNA helix. Although the centre of the operator is not in contact with protein, the repressor binding affinity can be reduced at least 50-fold by changing the sequence there: operators with A.T base pairs near their centre bind the repressor more strongly than do operators with G.C base pairs at the same positions. To explain these observations, it has been proposed that the base composition at the centre of the operator affects the affinity of the operator for repressor by altering the ease with which operator DNA can undergo the torsional deformation necessary for complex formation. In this model, the variation in binding affinity would require the torsion constant to have specific values and to change in a sequence-dependent manner. We have now measured torsion constants for DNAs with widely different base compositions. Our results indicate that the torsion constants depend only slightly on the overall composition, and firmly delimit the range of values for each. Even the upper-limit values are much too small to account for the observed changes in affinity of the 434 repressor. These results rule out simple models that rely on substantial generic differences in torsion constant between A.T-rich sequences and G.C-rich sequences, although they do not rule out the possibility of particular sequences having abnormal torsion constants. PMID- 2308637 TI - Pollution as Czech public enemy number one. PMID- 2308638 TI - Health risks: DoE to give up studies? PMID- 2308639 TI - Japanese science: polite bows to the West. PMID- 2308640 TI - AIDS meeting: WHO to aid Eastern Europe. PMID- 2308641 TI - Animal rights: new laws divide lawmakers. PMID- 2308642 TI - Conflict of interest: fierce debate at Harvard. PMID- 2308643 TI - Current opinion. PMID- 2308644 TI - Review needed of risks. PMID- 2308645 TI - Sexual attitudes. PMID- 2308646 TI - Fetus research. PMID- 2308647 TI - FDA pressure? PMID- 2308648 TI - Ovchinnikov defended. PMID- 2308649 TI - Conjoint report to the North Carolina Medical Society and the North Carolina Commission for Health Services. PMID- 2308651 TI - The present and future role of the county medical society. Where shall we go from here? PMID- 2308650 TI - The establishment of a population-based Cancer Registry for North Carolina. AB - In 1984 the North Carolina Medical Society's House of Delegates adopted Report S, which called for the North Carolina Legislature to fund a statewide cancer incident reporting system. The Cancer Committee continues to be advisory to the Division of Adult Health. A subcommittee of the Cancer Committee advises the Central Cancer Registry. PMID- 2308652 TI - Management of cerebrospinal fluid. AB - In traditional practice, doctors order tests and the laboratory performs them. A series of tests are requested before the results of any of the tests are known. The authors of this paper examine the interface between the clinicians and the laboratory. They produce a cost effective and clinically useful routine for handling spinal fluid. They bring to their practice an excellent example of quality assurance which is genuine, improves practice and is not "busy work." The editor heard Dr. Albright present this material and urged him to make it available to North Carolina doctors. PMID- 2308653 TI - Activated charcoal aspiration. PMID- 2308654 TI - Too many cesarean sections? PMID- 2308655 TI - How to cope with the peer review organization. PMID- 2308657 TI - Tornado trauma down on the farm. PMID- 2308656 TI - Hepatitis B: a preventable killer. PMID- 2308658 TI - Refractory congestive heart failure after ribavirin in infants with heart disease and respiratory syncytial virus. AB - Although treatment with ribavirin has been known to be associated with a decreased mortality in infants with congenital heart disease (CHD) who have respiratory syncytial virus (RSV), few data are available regarding morbidity. We reviewed records of 10 consecutively hospitalized infants with CHD during a recent RSV epidemic. Despite the presence of left-to-right shunt in each patient, symptoms of RSV were respiratory at presentation. After ribavirin, decreased respiratory symptoms were found in 8 infants but in 2 assisted ventilation were required 1 and 3 days after admission. Congestive heart failure worsened in 8 patients, 6 of whom had improved respiratory status after ribavirin. Of the 8 patients with worse CHF (pulmonary edema), 3 responded to medical management but 5 were refractory and 4 required surgical repair of CHD. One patient died of pulmonary hemorrhage. Medically refractory CHF may develop in infants with CHD who become infected with RSV and are treated with ribavirin. Further studies are needed to determine whether the pulmonary edema is caused by RSV, ribavirin, or combination of effects on pulmonary capillary function or some other unrecognized mechanism. PMID- 2308659 TI - [The DSM-III diagnostic inventory in patients with severe sleep disorders]. PMID- 2308660 TI - [Post-herpetic neuralgia: clinical predictors and psychopathologic findings]. AB - 48 patients, who had had acute Herpes zoster were screened for a retrospective investigation concerning the development of post-herpetic neuralgia. Subjects with and without neuralgia were compared with respect to medical, demographic and psychological variables. Nine patients were excluded from the investigation because of reported pain, which was not due to Herpes zoster. From the 39 subjects who remained in the analysis, 59% had postherpetic neuralgia for at least three months, and 28% for more than a year. No medical or demographic risk factor was sufficient for a prediction of the pain group. By applying objective criteria to psychometric test protocols, an index was constructed which differed between the groups. The pain-group showed a higher frequency of psychopathological impairment than those without post-herpetic neuralgia. However, the psychopathology was not consistently related to the length of neuralgia or the intensity of persistent pain. PMID- 2308661 TI - [Charles Bonnet syndrome in a Parkinson patient with bilateral visual loss]. PMID- 2308662 TI - [Anorexia nervosa, epileptic seizures and schizophreniform psychosis in temporo basal angioma]. PMID- 2308663 TI - [Responsibility of proof in research exemplified by the theory of the prevalence of early childhood experiences]. PMID- 2308664 TI - [Response to the letter by H. f. Durwen [Nervenarzt (1989) 60: 370] on the contribution by L. Hermle and G. Oepen. Hemispheric laterality and early childhood autism. Nervenarzt (1987) 58: 644-647]. PMID- 2308665 TI - The relationship between ventricular fluid pressure and body position in normal subjects and subjects with shunts: a telemetric study. AB - Using a chronically implanted telemetric pressure sensor, we have determined the quantitative relationship between changes in body position and ventricular fluid pressure in normal subjects and subjects with shunts. The method allows accurate, reliable measurement of negative as well as positive pressures. We describe the derangement of postural intraventricular pressure regulation caused by placement of a shunt, as well as the influence of various shunt systems and the antisiphon device on this problem. Ventriculoatrial, ventriculoperitoneal, and ventriculopleural shunts all caused similar severely abnormal postural intracranial pressure relationships. The antisiphon device was generally effective in restoring normal pressures in patients in the upright position. We discuss the implications of our findings for understanding the mechanisms of postural intracranial pressure regulation in patients without hydrocephalus. PMID- 2308666 TI - A study of the reactivity of feeding vessels to arteriovenous malformations: correlation with clinical outcome. AB - Isolated segments from the feeding arteries to arteriovenous malformations (AVMs) from 24 patients were studied in vitro. In a perfusion chamber, isometric contraction of these arterial rings to various vasoactive substances was recorded and correlated with the following: spontaneous activity, spasm as seen in the operating room; radiographic evidence of ectasia preoperatively and postoperatively; and postoperative course. Of the 24 patients studied, four patients had nonreactive AVM nutrient vessels upon in vitro testing. In addition, these vessel segments displayed no spontaneous activity although all of the other vessels tested developed spontaneous activity while in the perfusion chamber. The patients with "unreactive vessels" had an increased incidence of postoperative edema and hemorrhage in the surrounding brain, consistent with the symptoms of normal perfusion pressure breakthrough. Thus, our study utilizes an in vitro technique to evaluate a specific segment of the AVM complex, the feeding vessel, which permitted us to assess abnormalities of reactivity in these vessel segments. This method may be useful for future evaluations of the pathophysiology of AVMs. PMID- 2308667 TI - Neurosurgical applications of fibrin glue: augmentation of dural closure in 134 patients. AB - In a wide variety of neurosurgical procedures performed on 134 patients over a 3 year period, fibrin glue has been applied as an adjunct to dural closure. Overall success at preventing cerebrospinal fluid (CSF) leakage was 90% (121 of 134, 90% effective). In patients considered to be at high risk for CSF leakage intraoperatively but without pre-established fistulae (Group 1), the success rate was higher (111 of 119, 93% effective). In patients with pre-established CSF fistulae (Group 2), the success rate was lower (10 of 15, 67% effective). As single donor sources of concentrated fibrinogen are now available with reduced risks of blood-borne disease transmission, fibrin glue may be a valuable clinical tool for the neurosurgeon. PMID- 2308668 TI - Peri-epineurial tissue to supplement laser welding of nerve. AB - The principal difficulty with laser repair of nerves has been the inability to provide enough initial tensile strength to prevent separation of nerve ends. In previous experimental studies, dehiscence rates of laser-repaired nerves ranged between 12 to 25% whereas that for conventional epineurial suture repair was 0%. In our study, sciatic nerves of rats were transected bilaterally. Results of anastomosis by conventional epineurial suture on one side were compared with those of tissue welding by the CO2 laser using peri-epineurial sheath as a structural adjunct on the other side. At the time of reexploration at 7, 12, and 16 weeks, there was no dehiscence in nerves of either the laser with peri epineurial sheath group or the suture repair groups. Electrophysiological and morphometric values after use of peri-epineurial tissue as an adjunct to tissue welding by the CO2 laser were comparable to those of conventional suture repair. PMID- 2308669 TI - Magnetic resonance imaging and cervical spondylotic myelopathy. AB - Nineteen patients were examined for cervical spondylotic myelopathy with magnetic resonance imaging. Pre- and postoperative magnetic resonance scans were obtained in most cases. Surgical confirmation of the pathological condition was obtained for all 19 patients. On the T2-weighted scans, there was increased signal intensity within the spinal cord at the point of maximal compression. The exact cause of the increased signal intensity on the T2-weighted images is not known, but is suspected to represent edema, inflammation, vascular ischemia, myelomalacia, or gliosis. The increased signal intensity diminished postoperatively in the patients who improved clinically, and remained the same or increased in those whose conditions remained unchanged or worsened after decompression. The authors suggest that these T2-weighted images carry prognostic significance. PMID- 2308670 TI - Percutaneous automated biopsy in the diagnosis of primary infectious spondylitis. AB - Three cases of primary infectious spondylitis, two caused by Staphylococcus aureus and one by tuberculosis, were diagnosed using the method previously described for automated percutaneous discectomy. All three patients, in whom biopsy using fine needle techniques previously was unsuccessful, had positive cultures from specimens obtained using the automated method. The method combines the advantages of local anesthesia and minimal morbidity with the obtaining of adequate material for culture and pathological examination. PMID- 2308671 TI - The effect of pin location on the rigidity of the halo pin-bone interface. AB - Optimal insertion of halo fixation pins to maximize the rigidity of the interface between the halo pins and the outer table of the skull is important in reducing the incidence of pin loosening. An in vitro biomechanical study was performed using cadaver skulls to investigate the effects of pin location on the rigidity of this pin-bone interface. Halo pins were inserted at nine positions within a recommended "safe zone" for pin insertion. It was found that the rigidity of the pin-bone interface progressively decreased as pins were inserted more superiorly on the calvaria. The rigidity of the interface did not change significantly when the location of the pins was varied in the horizontal axis. This reduction in interface rigidity associated with inserting pins more superiorly on the skull may be related to an increase in the angle of insertion of the pins with respect to the surface of the calvaria. Based on this study, a change in the technique of halo pin insertion is recommended. Pins should be placed as inferiorly as possible, close to the supraorbital ridge, to achieve the most perpendicular angle of insertion and thus the most rigid fixation. The improved rigidity obtained with perpendicular pin insertion may minimize the rate of pin loosening and other complications associated with use of the halo orthosis. PMID- 2308672 TI - Management of hypothalamic gliomas in children: an analysis of 33 cases. AB - The cases of 33 children with hypothalamic-chiasmatic gliomas are reviewed. Radiation therapy produced clinical or radiographic improvement in 11 (46%) of 24 patients. Progression was documented in 18 patients (54%). Overall, the median time to tumor progression was 60 months; it was 70 months in patients who received radiation therapy and 30 months in those who did not (P less than 0.05). Chemotherapy, either given initially or at the time of progression, caused the tumor to respond or to stabilize in 10 patients. Partial resection of the tumor led to improvement in 3 of 12 patients, obviating the need for a shunt in 2 of them; there were no deaths and postoperative morbidity was transient and minimal (diabetes insipidus, intraventricular hemorrhage, and left hemiparesis in one patient each). The 5- and 10-year survival probabilities were 93 and 74%, respectively. Patients with neurofibromatosis had a better prognosis. PMID- 2308673 TI - L-buthionine-sulfoximine-mediated radiosensitization in experimental interstitial radiotherapy of intracerebral D-54 MG glioma xenografts in athymic mice. AB - An intracranial (i.c.) interstitial radiotherapy model in athymic nude mice bearing i.c. D-54 MG human glioma xenografts was developed, allowing evaluation of the therapeutic benefits seen after L-buthionine-S,R-sulfoximine (L-BSO) mediated depletion of tumor glutathione levels. Administration of L-BSO [2.5 mmol/kg intraperitoneal injections x 4 doses plus concomitant availability in acidified (pH 3.0) drinking water at a concentration of 20 mM] resulted in depletion of tumor glutathione levels to 0.15 mumol/g wet weight (7.9% of control). The therapeutic activity of i.c. interstitial radiotherapy with an 125I seed was enhanced after L-BSO-mediated glutathione depletion, with increases in median survival of 13.4 to 30.5% over that seen with 125I seeds alone. These studies demonstrate a potential role for BSO in enhancing the therapeutic activity of interstitial radiotherapy. PMID- 2308674 TI - Cerebral gliosarcomas: correlation of computed tomographic findings, surgical aspect, pathological features, and prognosis. AB - The cases of 5 patients with cerebral gliosarcomas examined by computed tomography are reported and the correlations among the computed tomographic (CT) findings, the surgical and histological aspects, and the prognosis are discussed. In some patients, these tumors appear on CT scan as intracerebral lesions, with large necrotic areas and peripheral contrast enhancement; this CT aspect, similar to that of glioblastomas, corresponds to a diffusely infiltrating growth of the tumor and the prevalence of a gliomatous component. In other patients, the tumor appears on the CT scan as a hyperdense mass with well-defined margins and homogenous contrast enhancement; this CT finding, which may mimic that of a meningioma, corresponds to a rather well-demarcated surgical aspect and the prevalence of sarcomatous component. In our series, we have also noticed a more prolonged survival in a patient with a CT aspect that suggested a meningioma and prevalence of the sarcomatous component. PMID- 2308675 TI - The effects of anesthesia on osmotic blood-brain barrier disruption. AB - To evaluate the effect of various anesthetic agents on hyperosmolar blood-brain barrier disruption (BBBD), Sprague-Dawley rats were given pentobarbital (PB), ketamine-xylazine (KX), isoflurane (IF), methoxyflurane (MF), or fentanyl droperidol (FD) before intracarotid infusion of mannitol or saline. Physiological monitoring showed that the effects of mannitol infusion differed significantly from those of saline infusion and were associated with transient bradycardia, hypotension, metabolic acidosis, and electroencephalographic depression. With PB, KX, or IF anesthesia, we obtained excellent BBBD as evidence by 3+ Evans blue staining of the mannitol-infused cerebral hemisphere. FD anesthesia was associated with tachycardia and MF anesthesia resulted in hypotension; both showed poor Evans blue staining. Radioisotope delivery to the disrupted hemisphere averaged 0.80% of the administered 125I-albumin compared to 0.03% in the contralateral and 0.06% in control (saline-infused) hemispheres. 99mTc glucoheptonate delivery measured 0.49% of the administered dose after BBBD, 0.03% contralaterally, and 0.05% in control hemispheres. Pharmacological manipulation to normalize the cardiac index in the FD and MF groups resulted in 3+ Evans blue staining and significantly increased delivery of albumin and glucoheptonate. This study suggests that the cardiovascular changes of these specific anesthetic agents are important in obtaining optimal hyperosmolar BBBD. PMID- 2308676 TI - Somatosensory and auditory brain stem conduction after head injury: a comparison with clinical features in prediction of outcome. AB - Evoked potential conduction times in brain stem auditory (BCT) and central somatosensory pathways (CCT) were recorded from 23 normal subjects and 101 patients with severe head injury. Abnormalities in the CCT and the BCT findings correlated with the clinical indices of brain damage (coma score, motor response, pupil response, and spontaneous and reflex eye movements) in the head-injured patients and each correlated with outcome at 6 months from the injury. The CCT in the "best" hemisphere produced the strongest correlation with outcome (P less than 0.001). The correlation of the CCT with outcome was stronger in the 47 patients examined 2 to 3 days after the injury (P less than 0.001) compared to the 34 patients examined within 24 hours after the injury (P less than 0.02). No such difference was noted for the BCT. Serial studies within the first 2 weeks of injury did not show a consistent pattern and repetition of the investigation over this period did not provide any additional information. We used an INDEP-SELECT discriminant analysis program to determine whether information from the evoked potential data could improve prediction of outcome based on clinical data alone. With the addition of the CCT, the predictive accuracy (expressed as the correct classification probability) increased only slightly from 77 to 80%, and the difference was not significant. We conclude that central somatosensory and auditory brain stem conduction times provide useful prognostic information in paralyzed or sedated patients, but when neurological examination is feasible the benefits of evoked potential analysis do not justify the effort involved in data collection. PMID- 2308677 TI - Transcranial magnetic stimulation of the facial nerve: recording technique and estimation of the stimulated site. AB - We compared transcranial magnetic and conventional electrical stimulation in 20 facial nerves of 10 normal subjects. A magnetic coil was placed tangentially over T5 or T6 (10-20 electroencephalogram electrode placement system) and electrical stimulation was applied 1 cm below the anterior tragus. Compound muscle action potentials recorded from the ipsilateral nasalis muscle showed onset latencies (mean +/- SD) of 4.48 +/- 0.50 ms with magnetic stimulation and 3.15 +/- 0.40 ms with electrical stimulation, a mean difference of 1.33 +/- 0.14 ms. Stimulation of the extracranial facial nerve at two sites yielded a conduction velocity of 59.6 +/- 4.5 m/s. Based on these findings, the magnetically stimulated site was estimated to fall 79.0 +/- 8.6 mm proximal to the point of electrical stimulation. Taking the average length of the nerve trunk and histological specificity of the root exit zone into consideration, evidence indicates that the root exit zone of the facial nerve is the most likely initiating site of excitation with magnetic stimulation. PMID- 2308678 TI - Recordings from human dorsal column nuclei using stimulation of the lower limb. AB - Responses from the surface of the dorsal column nuclei and the dorsal surface of the spinal cord were recorded using monopolar electrodes after stimulation of the lower limbs (common peroneal nerve at the knee and posterior tibial nerve at the ankle) in patients undergoing neurosurgical operations for spasmodic torticollis. Those responses were smaller in amplitude than responses to stimulation of the upper limbs (median nerve at the wrist), and the waveforms differed. The negative deflection that is prominent in the response to stimulation of the upper limbs is more variable, broader, and relatively smaller in amplitude than the response to upper limb stimulation. Another difference between responses to upper and lower limb stimulation was that multiple peaks were superimposed on the initial response to stimulation of the lower limbs, but were not as consistently seen in the responses to upper limb stimulation. The negative peak in the response from the dorsal column nuclei to lower limb stimulation was of about the same latency as the P27 peak in the far-field response (somatosensory evoked potential) to stimulation of the peroneal nerve. PMID- 2308679 TI - The management of paralytic spasticity. AB - The treatment of spasticity in severely paralyzed patients undergoing rehabilitation constitutes a significant neurosurgical challenge that requires comprehensive management. In this study, 118 patients were treated with invasive modalities when medical therapy failed. The results of percutaneous radiofrequency foraminal rhizotomy were initially successful in 95% of the 77 patients who underwent this procedure; the rate of minor complications was 5%. This procedure was satisfactorily supplemented with percutaneous radiofrequency sciatic neurectomy in 32 of these 77 patients. Four myelotomies were performed with complete success and no major complications in patients in whom percutaneous techniques had proven inadequate. In 35 instances of focal spasticity and incomplete paralysis, intramuscular neurolysis by phenol injection was used. The success rate was 89%. In 9 patients with persistent recurrent spasticity of the lower limb, open tenotomies and peripheral neurectomies were done. Success was complete and without complications. Multiple modalities must be available for the comprehensive management of patients with paralytic spasticity. PMID- 2308680 TI - Traumatic pseudoaneurysm of the cervical carotid artery: the value of arteriography. AB - A patient who sustained a gunshot wound to the neck and subsequent blunt trauma is presented. No angiogram was performed after the initial injury. Subsequently, the patient developed a cerebral embolus from a thrombus dislodged from a pseudoaneurysm of the cervical carotid artery, resulting in complete occlusion of the distal internal carotid artery. After antiplatelet therapy, the distal internal carotid artery recanalized, and the pseudoaneurysm occluded spontaneously. We stress the need for the use of arteriography in the initial evaluation of penetrating injuries to the neck and the utility of repeated arteriograms for further treatment planning as these traumatic lesions can change with time. PMID- 2308681 TI - Treatment of a giant aneurysm of the cavernous internal carotid artery associated with a persistent primitive trigeminal artery: case report. AB - A case of an unruptured giant aneurysm of the cavernous portion of the left internal carotid artery associated with a persistent primitive trigeminal artery (PTA) is presented. The usual surgical approach to giant aneurysms at this site, including ligation of the ipsilateral internal carotid artery (ICA) and an extracranial-intracranial (EC-IC) bypass, was inadequate because of continued blood supply to the aneurysm via the PTA from the vertebrobasilar system. The patient was successfully treated with a combination of EC-IC bypass surgery, ICA ligation, and simultaneous intravascular balloon obliteration of the ICA just distal to the junction of the PTA and immediately proximal to the aneurysmal neck. Follow-up radiological investigations showed thrombosis of the aneurysm. PMID- 2308682 TI - Congenital aneurysmal dilatation of the petrous-cavernous carotid artery and vertebral basilar junction in a child. AB - The occurrence of intracranial aneurysms in the pediatric population is a rare phenomenon. An unusual case of aneurysmal dilatation of both petrous and cavernous carotid arteries and the vertebral-basilar junction in a child is presented. The underlying etiology, natural history, and possible modes of management are reviewed and discussed. PMID- 2308683 TI - Arterial graft reconstruction in an aneurysm of the middle cerebral artery. AB - A case of a large aneurysm of the middle cerebral artery that was treated by resection of the aneurysm sac and reconstruction of the vessel is presented. The middle cerebral artery was reconstructed using a graft from the superficial temporal artery (STA). Cerebral vessel reconstructions are usually carried out with veins as grafts. This paper shows the possibility of using the STA as a graft. When a vessel reconstruction is contemplated, the skin flap should be planned in order to save the STA. PMID- 2308684 TI - Cerebral aspergillosis after burr-hole surgery for chronic subdural hematoma: case report. AB - We report a case of aspergillosis in the subdural space and frontal lobe in an 83 year-old man. The clinical course simulated that of a brain tumor. The source for the infection was considered to be the previous burr-hole surgery for chronic subdural hematoma, which was performed 2.5 years before the onset of symptoms. The patient was treated by removal of the abscess and granuloma. The clinical features and treatment of aspergillosis after neurosurgical procedures are discussed. PMID- 2308685 TI - Hyperprolactinemia in a patient with a pituitary and an ovarian dermoid tumor: case report. AB - A patient with galactorrhea, amenorrhea, and hyperprolactinemia caused by a dermoid tumor of the pituitary gland is presented. The patient had a prior history of an ovarian dermoid tumor. The pathology of dermoid tumors is discussed along with the management of pituitary tumor-associated hyperprolactinemia. This is the first reported case of an intracranial and an ovarian dermoid tumor occurring in the same patient. PMID- 2308686 TI - Management of cerebral astrocytomas in the adult. PMID- 2308687 TI - Pontine hemorrhage and trigeminal nerve impairment. PMID- 2308688 TI - Titanium for reconstruction of cranial defects. PMID- 2308689 TI - Sexual harassment and discrimination. Impact on physical and mental health. AB - Sexual harassment and sexual discrimination continue to be pervasive problems for women in business, academia, and medicine, with widespread and often serious health, emotional, and economic consequences. It is important that health care providers become aware of the common physical and emotional symptoms associated with these victimization experiences and serve as supportive and informed resources to their patients. PMID- 2308690 TI - Spacer-induced atrial fibrillation. AB - Inhaled sympathomimetics, studied extensively for treatment of asthma, have been found to be safe from cardiac arrhythmias. We discuss a case report of albuterol used with a spacer device that induced atrial fibrillation. We review relevant literature. PMID- 2308691 TI - Medical waste regulations. AB - Medical waste generators are subject to federal and state waste tracking and reporting regulations. Failure to comply with regulations can result in the imposition of significant penalties. PMID- 2308692 TI - Cutaneous malignant melanoma. AB - From January 1973 to December 1985, 136 patients with primary cutaneous malignant melanoma were treated at Englewood Hospital. Pathologic types, methods of treatment, and results are discussed and a comparison of results is made with other institutions. PMID- 2308693 TI - Strategic planning. PMID- 2308694 TI - Nursing education via the airwaves. PMID- 2308695 TI - Summer course for post RN students: fast-track options. PMID- 2308696 TI - Scholarly productivity of nurse educators with different types of doctorates. PMID- 2308697 TI - Recruiting the brightest and best for nursing--an honors program can help. AB - The severe shortage in nursing and significant decline in enrollments in schools of nursing present unique challenges. One way the University of Minnesota School of Nursing responded to this challenge was by initiating an honors program. The development and implementation throughout the first year are described. Funding, admission and graduation requirements, faculty work load, and the difficulties of introducing flexibility into typically highly structured undergraduate professional degree programs are addressed. Implications for the future are presented. PMID- 2308698 TI - A practical plan for teaching oral communication skills. AB - The authors describe an effective method of incorporating public speaking skills into a senior level nursing course. The topics included in the 5 hours devoted to communication strategies are listed. The method of student practice and the comprehensive manner of providing feedback are described. Recommendations are included for incorporating public speaking skills at the undergraduate level. PMID- 2308700 TI - Empowerment of nursing students. PMID- 2308699 TI - Pain content in the curriculum--a survey. AB - Freedom from pain is a basic human right and demands effective pain management. This survey reports what content related to pain management is being taught, where, and how. The author discusses minimal and essential content needed on pain management in baccalaureate nursing programs. PMID- 2308701 TI - Nursing issues: selection and analysis. AB - The authors describe the use of two strategies for selecting and analyzing issues. These systematic approaches provide a foundation not only for determining and studying issues, but also for implementing resolutions. Use of both processes makes dynamic, meaningful issues courses possible in nursing education. PMID- 2308702 TI - The use of hand-held calculators for solving pharmacology problems. PMID- 2308703 TI - Providing spiritual care. AB - Nurse educators are concerned about helping their students assess and meet their patients' spiritual needs. But how effective are we in doing this? This author wondered if professional nurses perceived themselves as being expected to provide spiritual care, believed it was part of the professional nurse role, and felt inadequately prepared educationally to provide spiritual care. The results of this study demonstrated a need for spiritual care content in basic nursing programs. The author differentiates between psychosocial/emotional needs and spiritual needs and presents strategies for teaching students and practicing nurses how to provide spiritual care. PMID- 2308704 TI - RN students teach generic students. AB - Faculty must develop teaching strategies that accommodate both generic and RN students. The author describes how she successfully integrated generic nursing students and RN students into the same physical assessment course. The teaching strategy described in this article resulted in satisfaction for the RN students, the generic students, and the instructor. PMID- 2308705 TI - Developing student confidence: the post clinical conference. PMID- 2308707 TI - Factors influencing food intake in man. The Thirteenth Marabou Symposium. Stockholm, June 16-18, 1989. Proceedings. PMID- 2308706 TI - Managing your academic career. Item analysis. PMID- 2308708 TI - Abstinence should take priority in 'critical messages' to send. PMID- 2308709 TI - Case study analysis of pseudocyesis: consideration of the diagnosis of child sexual abuse. AB - Pseudocyesis is a condition in which an individual has the symptoms of true pregnancy and believes that he or she is pregnant, but pregnancy does not exist. Pseudocyesis is not confined to one nationality, race, social class or sex, and clinicians may encounter this condition in practice. Physiologic, psychodynamic and social components of pseudocyesis are described. A case study is presented that illustrates the correlation between pseudocyesis and childhood sexual abuse. The importance of accurate assessment of childhood sexual abuse in successful resolution of the condition is emphasized. PMID- 2308710 TI - Identifying and helping children of alcoholics. AB - Though alcoholism is generally recognized as a disease, it is not widely recognized as a family disease reaching far beyond the alcoholic to affect the spouse, children and others with devastating consequences. It is estimated that 28 million Americans are children of alcoholics; 7 million are under age 18. These individuals are at high risk for developing alcohol-related physical and emotional problems. Current literature on children of alcoholics is relatively sparse, reflecting the limited amount of research and professional attention that has been given to this group. The treatment of alcoholism has focused primarily upon the alcoholic, while the children of alcoholics have been virtually ignored. This article describes the characteristics and roles of children of alcoholics in order to assist the health care provider in the identification of these individuals. A management approach is provided that can be used within a primary care setting for children of alcoholics. PMID- 2308711 TI - Nurse practitioners creating new horizons for the 1990s. PMID- 2308713 TI - Environmental challenges reduce eosinophils, produce symptoms. PMID- 2308712 TI - 'Duty to warn' vs. 'patient confidentiality': the ethical dilemmas in caring for HIV-infected clients. AB - An ethical dilemma that health professionals working with HIV-infected clients currently face is the issue of maintaining patient confidentiality vs. the professional's duty to warn persons at potential risk for acquiring the virus. Multiple factors are involved when trying to resolve what a health professional's obligations are when he or she becomes aware of a risk to another individual. Professional standards require that patient confidentiality be maintained in order to promote a helping relationship. Yet, the well-being of the one at risk must be considered. Legal precedents with other sexually transmitted diseases have been established that place the burden upon the clinician to warn in order to prevent litigation. Yet, an action on the part of the clinician should not be carried out just to prevent litigation. Actions that are taken should consider what is healthiest for all parties involved. Two cases are presented that cite specific instances in which a sexual partner was put at risk. A flow chart is presented that should assist in decision-making. PMID- 2308715 TI - Philosophical choices. PMID- 2308714 TI - We need more research. PMID- 2308716 TI - How to conduct a literature search. PMID- 2308717 TI - Types of research. PMID- 2308719 TI - Nursing needs nurses. PMID- 2308718 TI - Management in the private sector. PMID- 2308720 TI - The consultation liaison nurse. PMID- 2308721 TI - Nursing in Medway. PMID- 2308722 TI - The coronary patient and his spouse. PMID- 2308723 TI - The needs of visitors in intensive care. PMID- 2308724 TI - Cancer incidence in New Zealand born residents of New South Wales. AB - Cancer incidence in New Zealand born residents of New South Wales (NSW) has been compared with that in the Australian born population using data from the NSW Central Cancer Registry for the period 1972-84. Indirectly age-standardised incidence ratios (SIR) showed that New Zealand born women living in NSW had higher rates of cancer at all sites combined (SIR = 112) and a significant excess of colorectal cancer (SIR = 126). Although overall cancer rates were similar in men born in New Zealand to those in the Australian born men, the New Zealanders had a significantly higher risk of colorectal (SIR = 124) and testicular cancer (SIR = 227), cancers which are more common in New Zealand than in Australia. While the SIRs for lung cancer in men and melanoma of skin in both sexes were low, no cancer was significantly less common in New Zealand born residents of NSW than in the Australian born. PMID- 2308725 TI - Prevalence of chlamydial antibodies in women with tubal disease: impact of Chlamydia trachomatis on the demand for in vitro fertilisation. AB - Serum IgG and IgA antibodies to Chlamydia trachomatis were measured in 102 in vitro fertilisation (IVF) patients with tubal disease and in 102 infertility patients without tubal disease to assess the impact of chlamydial infection on the demand for IVF treatment in New Zealand. Sixty-five percent of the IVF patients had IgG titres greater than or equal to 1:64, compared to 24% of the controls; 29% of the IVF patients had IgA titres greater than or equal to 1:32 compared to 0% of the controls. The proportion of IVF patients with IgG antibodies increased from 39% for those from socioeconomic group 1 to 79% of those from groups 4 to 6. The difference in prevalence of IgG antibodies between the tubal and nontubal patients suggests that about 40% of the tubal infertility currently being treated by IVF has chlamydia as a causal agent. The presence of IgG or IgA antibodies did not seem to affect the chance of pregnancy in the IVF programme, nor the chance of subsequent miscarriage. PMID- 2308726 TI - National bioethics committees: developments and prospects. PMID- 2308727 TI - The extent of breast feeding in Dunedin 1974-83. AB - This study examined breast feeding practices in Dunedin, and aimed to identify determinants of breast feeding in this population. Infants' records were used for a 10 year period (1974-83) from the Royal New Zealand Plunket Society. An upward trend in breast feeding prevalence was observed. Breast feeding was more common in mothers of high socioeconomic status (p less than 0.001), in those who were living with a spouse (p less than 0.001) and when mothers attended parental classes (p less than 0.025). First time mothers tended to breast feed for a shorter time (p less than 0.05). Early introduction of other foods shortened the duration of breast feeding (p less than 0.001). The increase in breast feeding which has occurred in many parts of the western world was also found in Dunedin. PMID- 2308728 TI - How do Christchurch parents keep young babies warm on cold nights? AB - To find out how sleeping babies are kept warm on cold nights, the parents of 235 babies born during June 1986, and under Plunket supervision, completed a questionnaire during August/September of that year, detailing the clothing, bedding and heating arrangements for their baby for the previous night. One hundred and twelve (52%) babies slept in rooms with thermostatically controlled heating on all night and 65 (28%) slept in essentially unheated houses. The combined amount of clothing and bedding (number of layers over the torso) covering infants ranged from three to 12 layers with a mean of 7.0 layers (SD 1.79). There was no relationship between the number of total coverings and the use of heating so that babies in rooms heated directly were just as likely to be covered by a lot of clothing and bedding as babies in rooms with no direct heating. An unexpected finding was the wide range of practices between Plunket clinics. The mean number of total coverings for babies grouped by clinic attended ranged from 5.2 layers (n = 5) to 9.1 layers (n = 16). The finding that the use of heating in a baby's room is not related to the amount of total coverings, suggests that this practice could put some babies at risk of thermal stress. PMID- 2308729 TI - Fenoterol and asthma mortality in New Zealand. PMID- 2308730 TI - Blood lipids and meals. PMID- 2308731 TI - Lead exposure in a general practice. PMID- 2308732 TI - Informed consent and economic efficiency. PMID- 2308733 TI - Waitangirua health centre and the provision of services. PMID- 2308734 TI - Solo general practice. PMID- 2308735 TI - Monitoring noise levels. Interview by Michael Bangs. PMID- 2308736 TI - Racial tolerance--what is the law? PMID- 2308737 TI - Stress sickness. Prison riots and absentee counselling--an unexpected bonus. PMID- 2308739 TI - What makes a good occupational first-aider? PMID- 2308738 TI - Biohazards: micro-organisms. Interview by Rosemary Cox. PMID- 2308740 TI - COSHH: adverse side effects. Interview by G Nagle. PMID- 2308741 TI - Pulmonary function tests, histories keys to recognizing lung disorders. PMID- 2308742 TI - Protection from asbestos exposure includes personal and area monitoring. PMID- 2308743 TI - Occupational risks of chemical use may be greater in small businesses. PMID- 2308744 TI - Electronic work-place surveillance threatens dignity, quality of life. PMID- 2308745 TI - The growth of professional optometry. PMID- 2308746 TI - Effect of induced dynamic aniseikonia on fixation performance during oblique gaze. AB - This is a sequel to other papers dealing with the effect of induced aniseikonia and optical anisophoria on fixation eccentricity during bifixation. To stimulate the effect of induced anisophoria, controlled amounts of differential prism were induced in the vertical meridian. At the same time, stimuli were presented at various angles from the subject's straight ahead orientation. As demonstrated in other studies, it was found that a vertical prismatic difference will cause the eyes to fixate slightly eccentrically in the horizontal meridian. The eccentricity was measured with the border enhancement method, described and tested in other studies. In addition, it was found that the fixation deviation is increased further by oblique gaze, the greatest obliquity having the greatest effect. It was also found that whereas short-term adaptation reduces the prism effect somewhat, it has less influence on the effect of oblique gaze. In general, the study demonstrates the potential oculomotor problems inherent in optical anisophoria. PMID- 2308747 TI - Rigid lens base curve stability upon hydrogen peroxide disinfection. AB - Because of the possibility of transmitting communicable diseases, in particular the HIV virus, it has been recommended that all diagnostic contact lenses, including rigid lenses, be disinfected after each use. Hydrogen peroxide is a recommended disinfection agent, but its effect on rigid lens polymers is relatively unknown. We soaked 50 lenses of 5 different polymers in 3% hydrogen peroxide for 10 min and measured the base curves to determine if any changes occurred. Our results showed no statistically significant change in base curve for the lenses measured, but 22% of the lenses did exhibit a small amount of warpage (mean 0.0382 mm) of the base curve. We were not able to determine what caused these lenses, and not all the lenses, to warp. Under the conditions of this study, hydrogen peroxide does not appear to cause clinically significant parameter changes, but lenses should be checked for warpage before use. PMID- 2308748 TI - Proximal vergence and perceived distance. AB - Proximal vergence was measured haploscopically in response to a change in physical distance of a large screen of blurred horizontal lines. These responses were compared to proximal vergence measurements made using a clinical method. Perceived distance of the horizontal stripes was estimated according to the perceived size of a projected afterimage. For 18 normal observers the change in vergence measured haploscopically (in prism diopters per meter angle change in test distance) averaged 2.59 (SD = 1.44) binocularly and 2.11 (SD = 1.22) monocularly. Clinical measures averaged 2.88 (SD = 1.57) binocularly and 2.10 (SD = 1.27) monocularly. Haploscopic and clinical measures of proximal vergence correlated only when the clinical technique was modified by viewing through pinholes. Taking estimated perceived distance into consideration only partially reduced the differences between proximal vergence measured haploscopically and clinically as well as binocularly and monocularly. Both haploscopic and clinical measures of proximal vergence were sizeable, indicating that this vergence component can contribute significantly to the normal vergence response. PMID- 2308749 TI - Effects of dioptric blur on Snellen and grating acuity. AB - We compared the effects of dioptric blur on Snellen acuity and grating acuity. Dioptric blur had a strong negative effect on Snellen acuity, consistent with previous studies, but had little effect on grating acuity. Between 1 and 12 D both types of acuity were reduced as a linear function of blur. However, 12 D of blur reduced grating acuity to only 6/24 (20/80), whereas letter acuity was worse than 6/300 (20/1000). We suggest that these differences are due to the presence of "spurious resolution" in which phase-reversed gratings are readily detectable. But the phase reversals so distort the relative positions of linear segments within the letters that the letters become unrecognizable. These results indicate that Snellen letters are more sensitive than gratings to a patient's refractive errors, emphasize the differences between Snellen and grating acuity, and indicate that the minimum angle of resolution (MAR) concept is not applicable to letters. PMID- 2308750 TI - Elements of the dioptric power matrix and the concept of torsional power: a reinterpretation. AB - The elements of the dioptic power matrix have previously been interpreted in terms of power along particular meridians with the off-diagonal elements interpreted as a new form of dioptric power called torsional power. This paper shows that such new concepts are not necessary. Decomposition of the matrix provides an interpretation in terms that are quite familiar. The elements represent three component powers: the diagonal elements are two cylinders and the off-diagonal elements a crossed-cylinder with axes at 45 degrees and 135 degrees. The component crossed-cylinder obviates the need for the concept of torsional power. The concept of meridional power is avoided. PMID- 2308751 TI - Visual characteristics of low vision children. AB - A retrospective survey of pediatric clinical files from the Kooyong Low Vision Clinic (LVC) showed that the major causes of low vision were congenital or inherited conditions and most children had 6/60 (20/200) or better distance acuities. A classroom evaluation of these children showed that overall, the clinically determined visual acuity corresponded with classroom performance. A high rate of use of prescribed low vision aids was found, and a reading evaluation on a standardized test showed poor performance with respect to reading speed and comprehension, but almost all the children had adequate reading accuracy. Considering the importance of reading in education, greater emphasis on reading evaluations in routine low vision examinations is recommended. PMID- 2308752 TI - Visual acuity for optotypes made visible by relative motion. AB - There are several visual mechanisms for analyzing spatial information additional to the much researched mechanism sensitive to luminance contrast. We describe a Snellen-type acuity test for motion-defined (MD) letters. Acuity for these MD letters collapsed at dot speeds slower than 0.05 deg/s, but acuity for contrast defined (CD) letters was unaffected by speed over the entire 0 to 0.3 deg/s range used. Acuity was a power function of presentation duration for both kinds of letter, but the exponent was higher for MD than for CD letters. Acuity for MD letters was comparatively unaffected by dot density from 50 to 0.05%, below which it suddenly collapsed to zero. On the other hand, acuity for CD letters progressively fell as dot density was reduced from 50%, and below about 0.5% approximated acuity for MD letters. PMID- 2308753 TI - Oligodendroglioma--a case presentation. AB - Cerebral oligodendroglioma is a rare form of malignant tumor. Oligodendroglioma represents 5% of all gliomas. Our patient is a 12 1/2-year-old white female who presented with suddent onset of disc edema, esotropia, and field loss, who 2 weeks before had a normal fundus. The diagnosis is right occipital oligodendroglioma. PMID- 2308754 TI - The Photographic Method for Bruckner and Hirschberg Testing. PMID- 2308755 TI - Statistics notebook: entry I.I., fine points of distribution shape, (1) skewness and (2) kurtosis. PMID- 2308756 TI - Effects of dioptric blur on the Vistech contrast sensitivity test. AB - We studied the effect of dioptric blur on contrast sensitivity using the Vistech Vision Contrast System Chart. One diopter of blur affected the Vistech gratings by an amount consistent with expectations; sensitivity loss was greatest with higher spatial frequencies. However, a second diopter of blur induced an equal sensitivity loss for all spatial frequencies. A third diopter induced the greatest loss at the lowest frequency and an actual increase in sensitivity at the highest frequencies. This surprising finding is due to an interaction between "spuriously resolved" gratings and the border of the grating disc which resulted in the finest grating discs appearing to contain low frequency borders aligned with the fine gratings. Actually the fine gratings in the disc were invisible. When performing scanning photometry on the Vistech chart, we found that the contrasts of the unblurred gratings with higher contrast levels are 2.7 to 5.4 times higher than those stated by the manufacturer. The presence of this aliasing artifact indicates that the Vistech Vision Contrast System may produce erroneous results when used under conditions of high dioptric blur. PMID- 2308757 TI - Department of Health needs your help in 'getting the word out'. PMID- 2308758 TI - Self-administration of morphine in bone marrow transplant patients reduces drug requirement. AB - Bone marrow transplant recipients were randomly assigned to receive morphine by either continuous infusion (32 patients) or self-administration of small boluses (patient-controlled analgesia (PCA), 26 patients) for control of chemoradiotherapy-induced oral mucositis pain. All patients received morphine for a minimum of 9 days and most required morphine for at least 14 days. Patients rated their pain and side-effect intensity daily using visual analogue scales. Patient pain ratings did not differ between the groups although PCA patients used only 53% as much morphine as the continuous infusion group. Tolerance did not develop in the PCA group; in patients receiving continuous infusion morphine dosage continued to increase throughout the study while pain scores remained constant, indicating that tolerance had developed. Nausea, alertness and respiratory rate measurements did not differ between groups. PCA appeared more effective than the hospital staff determined treatment at delivering the least amount of morphine required to produce maximal pain relief. Patients self administering morphine did not appear to restrict morphine intake in order to minimize opioid side-effects. PMID- 2308759 TI - Benzydamine cream for the treatment of post-herpetic neuralgia: minimum duration of treatment periods in a cross-over trial. AB - In a double-blind multiple-dose cross-over study benzydamine 3% cream was compared with placebo for the treatment of post-herpetic neuralgia. Pain relief, pain intensity, sleep, escape analgesic consumption and side effects were assessed by diary methods for the 2 week treatment periods, with 1 week run-in and 1 week wash-out. There were no significant differences between the 2 treatments. The implications of the results for other antiprostaglandin remedies recommended for treatment of post-herpetic neuralgia are discussed. An important observation with methodological significance for similar studies of chronic conditions was that short treatment periods may produce false positive results. Patients' expectations are high, and if the first study treatment is ineffective, initial significant benefit may be noted when crossing over to the next treatment; this may not last longer than 1 week. Cross-over studies in which neither treatment is effective may, therefore, produce erroneous results if treatment periods are shorter than 2 weeks. PMID- 2308760 TI - A comparison of the effects of intrathecal fentanyl and lidocaine on established postamputation stump pain. AB - Eight patients with established lower limb postamputation stump pain were given lumbar intrathecal fentanyl 25 micrograms and lidocaine 70 mg 2 weeks apart in an attempt to better understand the role of peripheral and central mechanisms in this condition. Baseline pain was recorded and then analgetic and side effects and their duration were assessed. Three self-administered questionnaires with appropriate psychometric proprieties were given to the patients. Intrathecal fentanyl always abolished the pain. Its onset was rapid being heralded within 1 2.5 min by a pleasant sensation of warmth involving the lower trunk and legs. Analgesia was complete by 5-10 min and had a median duration of 8 h. The patients had a sense of well being and were unable to elicit discomfort by pain aggravating maneuvers. Normal motor and sensory functions were retained. Pruritus was the only adverse effect unique to intrathecal fentanyl. Intrathecal lidocaine usually relieved the discomfort but was unable to abolish it in 3 of 8 patients despite adequate neural blockade. Its onset of action was slower and duration of effect shorter than fentanyl. Intrathecal fentanyl provided profound analgesia associated with normalization of stump sensations and euphoria, probably due to a segmental spinal action. The effects of lidocaine were inferior to fentanyl due to the associated motor and sensory paralyses as well as the absence of euphoria. This study suggests that, while peripheral mechanisms played a role, central mechanisms involving the spinal cord were more important in the modulation of established stump pain in the 8 subjects evaluated. PMID- 2308761 TI - Comparisons between patients' and nurses' assessment of pain and medication efficacy in severe burn injuries. AB - In order to provide burn patients with adequate pain relief, the nurses must be able to accurately evaluate the patients' pain levels and to assess whether sufficient analgesia is achieved or not. The present study examined this issue by comparing the pain ratings in 42 patients hospitalized for burn injuries and 42 nurses. The patient and the attending nurse were asked to rate, independently of each other, the intensity of the pain felt by the patient during a therapeutic procedure and at rest. When analgesic medication was given prior to the procedure, both the patients and the nurses were asked to estimate the degree of pain relief. All ratings were obtained using visual analogue and verbal scales. The results revealed significant but small correlations between the nurses' and patients' ratings. Frequently, the nurses underestimated or overestimated the patients' pain. Discrepancies were also observed in the evaluation of pain medication efficacy, the nurses showing a tendency to overestimate the degree of pain relief. The accuracy of the nurses' perception did not vary as a function of the patients' age, socioeconomic status or burn severity. However, the number of years of experience in burn-nursing had a significant influence on the nurses' estimation of the patients' pain during therapeutic procedures. Theoretical and clinical implications of these results are discussed with a particular emphasis on the need to implement systematic procedures to assess pain and success of analgesia. Additional recommendations to optimize pain management in burn patients are also made. PMID- 2308762 TI - Psychological defence mechanisms in patients with pain. AB - There is a long standing position that pain, and especially chronic pain, may arise from psychological mechanisms of defence. We have compared a group of chronic pain patients with a sample of psychiatric patients attending for reasons other than pain. The pain group had less evidence of poor care in childhood (measured by the Parental Bonding Instrument) and tended to use more mature psychological defence mechanisms (assessed with the Defense Mechanisms Inventory), compared with the other group. The pain group also had fewer current psychiatric diagnoses but more evidence of anxiety and depression on the Hospital Anxiety and Depression Scale. We conclude that in general the patients with chronic pain had more normal childhoods and more mature defences than the psychiatric control group. They showed an increase in the diagnosis of depression, attributable to reactive factors. In the sample of patients with pain the majority of the psychological change cannot be attributed to the operation of primitive psychological defences. PMID- 2308763 TI - The Pain Disability Index: psychometric properties. AB - This paper reports two studies of chronic pain patients (n = 444) relevant to the psychometric properties of the Pain Disability Index (PDI), a self-report instrument that has been used to assess the degree to which chronic pain interferes with various daily activities. In the first study, patients with high PDI scores reported more psychological distress (P less than 0.001), more severe pain characteristics (P less than 0.001), and more restriction of activities (P less than 0.001) than patients with low PDI scores, findings supportive of the construct validity of the measure. Further, a multiple regression showed that a linear combination of 9 variables predicted PDI scores (R = 0.74): time spent in bed, psychosomatic symptoms, stopping activities because of pain, work status, pain duration, usual pain intensity, quality of life, pain extent, and education. This study also showed differences for age and gender on disability. The second study involved 46 patients who had undergone inpatient treatment for their pain conditions. The study revealed modest test-retest reliability for the instrument. It also showed the PDI to be associated with the levels of pain behavior exhibited by these patients. The findings of both studies generally support the reliability and validity of the PDI as a brief measure of pain-related disability. Questions regarding its test-retest reliability and lack of association with certain pain behaviors are discussed, as are suggestions for future research. PMID- 2308764 TI - Non-institutional treatment of chronic pain by field management: an outcome study with comparison group. AB - Field management, through the use of specially trained field consultants, is a mechanism by which interdisciplinary interventions can be implemented in non institutional settings. Management of the real environmental determinants (home, work, social) of pain and disability should improve the effectiveness of behaviorally based interventions and make these treatments more accessible. Over a 6 year period, 261 patients having various chronic somatic complaints (e.g., pain, fatigue, gastrointestinal complaints) underwent interdisciplinary outpatient treatment based on medical and behavioral sciences. Comparison of patients having field management with patients receiving office-based treatment found a significantly greater reduction in disability with field management. 84% of field managed patients had a successful outcome as defined by: (a) return to regular work, or (b) reduced limitations on work, exercise, and daily living activities, depending on functional status at assessment. Only 61% of patients with office-based treatment were successful. Compliance, defined as the frequency with which treatment was mutually terminated, was significantly higher with field management. The availability of long-term disability benefits was highly predictive of a poorer outcome. However, field management remained effective for improving functional status regardless of the availability of benefits. Finally, determination of the cost of non-institutional treatment indicated that field management is a cost-effective modality. Implications of these findings for the treatment of disability in chronic pain and other chronic illness syndromes are discussed. PMID- 2308765 TI - The effect of GABA and its antagonists on midbrain periaqueductal gray neurons in the rat. AB - Injection of GABA into the midbrain periaqueductal gray (PAG) activates medullary neurons that are involved in pain inhibition and potentiates morphine-induced analgesia. These observations suggest that GABAergic mechanisms in the PAG may modulate the descending pain inhibitory system that arises from this structure. In the present study, the effects of GABA and GABA antagonists on membrane properties and baseline activity of PAG neurons were examined using both in vitro and in vivo preparations. Application of bicuculline methiodide (BICM), at a dose that blocked the response to GABA, potently increased the baseline firing rate in 53% of cells recorded in vitro and 74% of cells recorded in the intact preparation. Application of BICM often yielded multiple or burst spiking episodes in both preparations. In 69% of cells the effect of BICM was diminished or totally abolished when the slice was perfused with high-magnesium, calcium-free, physiological saline solution. Intracellular recordings revealed that bicuculline caused depolarization of the membrane (70% of cells), increased the firing frequency (94% of cells) and increased the frequency of excitatory postsynaptic potentials (18% of cells). The effect of bicuculline on membrane resistance was not pronounced and in 64% of neurons it did not cause any measurable change in the resting membrane resistance. PAG neurons responsive to GABA and its antagonists were observed in all regions of the PAG. However, the highest number of neurons that responded to GABA and its antgonists was found in the medial and medioventral parts of the PAG. These results indicate that PAG may contain a tonically active GABAergic network that operates, at least in part, through GABAA receptors. This GABAergic system may modulate activity in descending pain inhibitory pathways emanating from PAG. PMID- 2308766 TI - Tonic 5-HT modulation of spinal dorsal horn neuron activity evoked by both noxious and non-noxious stimuli: a source of neuronal plasticity. AB - The influence of tonic serotonergic modulation on the responses of spinal dorsal horn neurons to natural peripheral stimulation was examined in physiologically intact, awake, drug-free cats. Systemically administered methysergide (maximum cumulative dose 2 mg/kg) caused significant changes in responses of some dorsal horn neurons to both mildly noxious and non-noxious stimulation. Individual changes provide evidence, in this model, for tonic 5-HT modulation of many aspects of sensory transmission at the level of the spinal cord. Taken together, the changes demonstrate the significant degree of plasticity that exists for some spinal dorsal horn neurons. It is clear that the plasticity of some spinal dorsal horn neurons allows for a much broader response profile than would be apparent under the restricted circumstances of a normal neurophysiologic study. Removal of tonic inhibition on responses to noxious stimuli may be an aspect of neuronal plasticity that functions to provide an immediate change in the way that the nervous system responds to a noxious stimulus. PMID- 2308767 TI - The effects of bradykinin agonists and antagonists on visceral polymodal receptor activities. AB - The endogenous algesic agent bradykinin (BK) is a consistent stimulant for the polymodal receptor, a type of nociceptor. Two types of BK receptor, B1 and B2, have been proposed in smooth muscles by Regoli. The type of BK receptor mediating the BK response of the polymodal receptor was studied using 3 BK analogs, des Arg9-BK (a B1 agonist), des-Arg9-[Leu8]-BK (a B1 antagonist), and [Thi5,8, D Phe7]-BK (a B2 antagonist). Single- and multi-fiber activities from testicular polymodal receptors were recorded in vitro using testis-spermatic nerve preparations excised from dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Neither des-Arg9-BK, des-Arg9-[Leu8]-BK, nor [Thi5,8,D-Phe7]-BK induced discharges in nociceptors at concentrations up to 9.4 x 10(-6) M. Des-Arg9-[Leu8] BK (up to 9.4 x 10(-6) M) did not suppress responses to BK (9.4 x 10(-8 approximately -9) M), whereas [Thi5,8,D-Phe7]-BK (above 2.8 x 10(-7) M) suppressed the BK response in a concentration-dependent manner and shifted the concentration-response curve of BK to the right. It was ascertained that [Thi5,8,D-Phe7]-BK had no effect on responses to noxious heat and high K+ solution. These results suggest that the BK receptor mediating the nociceptor response to BK is of the B2 type. PMID- 2308768 TI - The rat paw formalin test: comparison of noxious agents. AB - A comparison was made of the spontaneous nociceptive behaviors elicited by s.c. injection into the rat hind paw of the following 8 irritants: acetic acid, carrageenan, formalin, kaolin, platelet-activating factor, mustard oil (given topically), serotonin, and yeast. Two distinct quantifiable behaviors indicative of pain were identified: flinching/shaking of the paw and hindquarters and licking/biting of the injected paw. These behaviors were prolonged and intense after formalin and acetic acid. Formalin-induced flinching was biphasic across time, a finding potentially useful for the study of both acute and tonic pain. Of the remaining test agents, only yeast caused significant spontaneous behavioral activity, which was of low intensity but long duration. Different time-courses for nociceptive behavior and development of edema were demonstrated for formalin, acetic acid and yeast. It is therefore unlikely that these endpoints are causally related. Overall, the present data strongly support the use of formalin as a noxious stimulus in tonic pain research. PMID- 2308770 TI - Abstracts of the Sixth World Congress on Pain. Adelaide, Australia, 1-6 April 1990. PMID- 2308769 TI - Comments on 'A dorsolateral spinothalamic tract in macaque monkey' by Apkarian and Hodge. PMID- 2308771 TI - Troubleshooting arthroscopic equipment. PMID- 2308772 TI - Self-care needs of patients in the halo brace. AB - This retrospective, descriptive study examined the wishes, concerns, and experiences of patients who had been placed in a halo brace to treat a cervical fracture. Thirty-eight subjects who had a halo brace applied during the past 8 years completed the questionnaire. Data obtained reflected physiologic as well as psychosocial needs of these patients. Responses were categorized based on nursing diagnoses. Results demonstrated the need for more specific information given to patients before discharge from the hospital to facilitate adjustment to the halo brace and activities of daily living. PMID- 2308773 TI - Collaborative development of a standardized order form for orthopaedics. AB - Standardization of treatment parameters is key to facilitating accurate initiation of orthopaedic patient care. A standard "Postop Orthopaedic Orders" form was developed via a collaborative effort among orthopaedic nurses, physicians, and unit secretaries. Its purpose was to improve the completeness of physicians' orders, efficiency of order transcription, and speed initiation of the therapeutic regime. PMID- 2308774 TI - In-hospital case management. Responses to common questions and concerns. PMID- 2308775 TI - An interview at Robert Wood Johnson University Hospital. ProACT model. AB - In its deliberations on the shortage of nurses, the Executive Board of NAON charged the Orthopaedic Nursing journal with bringing information to our readers concerning innovations in nursing care which have resulted partly in response to the current nursing crisis. This article presents an innovative care model implemented on an orthopaedic unit at Robert Wood Johnson University Hospital in New Brunswick, New Jersey. It describes not only the developed system but also the process that was used in implementing the design. PMID- 2308776 TI - Disabled on two shores. AB - When the author arranged to study anthropology in England in 1988, little did he suspect the vast differences in societal attitudes toward disabled people. This article highlights many of the situations he encountered during the year he and his wife spent in England. PMID- 2308777 TI - Valsalva maneuver as a possible risk factor for pulmonary embolism. AB - Valsalva maneuver has been suspected of precipitating pulmonary embolism (PE), but the association of the two variables has not been studied. The purpose of this retrospective study was to begin to investigate whether Valsalva behavior is associated with subsequent PE. The frequency of Valsalva behaviors prior to confirmed PE in 30 patients was compared to the frequency of Valsalva behaviors in 60 non-PE patients, randomly selected from patients matched with the study group for age, sex, and year of hospitalization. PMID- 2308778 TI - [Interleukins and inflammation]. AB - Interleukins (IL) are a heterogeneous class of cytokines involved in activation of T lymphocytes (IL-1, 2, 4, 6 and 7), B lymphocytes (IL-1, 2, 4, 5, 6 and 7), and macrophages (IL-1 and 4), and hematopoiesis (IL-1, 2, 3, 4, 5, 6 and 7), acting either by themselves, or as co-stimulator factors. Interleukin-1 (IL-1 alpha and IL-1 beta) is induced by different signals including microbial products; it mediates various events occurring during inflammation (e.g. fever, osteolysis, leucopenia, hypotension, hyperalgia, etc...). Such mechanisms are often the consequences of the induction by IL-1 of lipid mediators (e.g. prostaglandins, platelet activating factor, etc). IL-1 often acts synergistically with Tumor Necrosis Factor during the pro-inflammatory process. IL-1 as well as microbial products induces the production of interleukin-6 and interleukin-8. IL 6 also plays a role in inflammation, mainly as an inducer of acute phase proteins synthesis by hepatocytes. IL-8 has chemotactic and activating properties for neutrophils. PMID- 2308779 TI - [Regulation of antibody production by monokines and glucocorticoids]. AB - The antibody production by B lymphocytes is regulated by a number of interleukins produced by T lymphocytes and/or monocytic cells: IL-1, IL-2, IL-4, IL-5, IL-6 and interferons. This response is also under the influence of other mediators such a glucocorticosteroid hormones. The in vivo administration of pharmacological doses of steroids do not markedly suppress the in vivo antibody response to exogeneous antigens. This is due to a contrasting effect: they prefoundly inhibit the production of most interleukins whereas they directly stimulate B lymphocyte response. We recently analyzed the mechanisms of this latter phenomenon and showed that glucocorticosteroids synergize with the monocyte-derived cytokines IL-1 and IL-6 to potentiate the in vitro B lymphocyte differentiation. PMID- 2308780 TI - [Involvement of tumor necrosis factor in the generation of LAK killer cells]. AB - The effect of Tumor Necrosis Factor (TNF) alpha on LAK generation was investigated. TNF was found to act synergistically with low concentrations of IL 2 (15 pM), which were ineffective by themselves to promote the differentiation of Large granular lymphocytes (LGL) into LAK effectors. The IL-2/TNF driven generation of LAK activity involves the induction of high affinity IL-2 receptors on LGL and occurs without promoting a significant proliferation, suggesting a functional activation rather than a proliferative expansion of LAK precursors. Our studies also indicate the existence of a correlation between the generation of LAK activity and the increase in TNF binding sites on LGL. Furthermore we demonstrate that the failure of low doses of IL-2 to induce LAK activity were related to their incapacity to induce TNF production by LGL and suggest that TNF alpha may be a physiologic mediator in the sequential activation stages of LGL into LAK effectors. PMID- 2308781 TI - [Viruses and malignant hemopathies]. AB - Review on general problems raised by the role of some viruses: parvoviruses, herpes viruses, retroviruses, in the physiopathology of human malignant blood diseases. PMID- 2308782 TI - [THP-adriamycin: status of the clinical development of a new anthracycline in France]. AB - THP-adriamycin (pirarubicin) is a new anthracycline-analogue. In France, the drug is achieving the phase II studies and the step of phase III studies is going on. As this point of its development, it is already possible to conclude that the drug probably shares the same efficacy as adriamycine, especially in breast cancer, but exhibits a better tolerance in term of alopecia and cardiac toxicity, as predicted by preclinical studies. Its pharmacological properties make the drug an original compound, exciting for investigations in the field of loco-regional therapy. PMID- 2308783 TI - [Application of derivative spectrophotometry for determining plasma hemoglobin and semi-quantitative evaluation of urinary porphyrins]. AB - We described a method using second-derivative spectrophotometry with a spectrophotometer Uvikon (Kontron) for the assay of plasma hemoglobin and urinary porphyrins. We evaluated the procedure for sensitivity, linearity, analytical recovery. Non specific interference is not significant and reproductibility is excellent. This simple, rapid, sensitive, not expansive method can be adapted for use in a clinical laboratory. PMID- 2308784 TI - [Promoting French participation in the experimentation on neuronal grafts for therapeutic purposes]. PMID- 2308785 TI - A pediatrician's view. PMID- 2308786 TI - A practical approach to dysmorphology. AB - Accurate diagnosis is essential to providing appropriate care for children with congenital anomalies. PMID- 2308787 TI - Congenital heart disease. PMID- 2308789 TI - Care: the imperative of nursing education and service. PMID- 2308788 TI - Value and limitations of auscultation in the management of congenital heart disease. AB - With advances in technology, especially that of ultrasonography, the art and science of auscultation could become relegated to that of an obsolete technique. Physicians in a cardiovascular training program involved in learning modern instrumentation diagnostic techniques often become expert in these areas before they have mastered the use of the stethoscope. Although the technology of ultrasonic examination, cardiac catheterization, and angiocardiography must be learned, the value of auscultation of the heart cannot be ignored. Many highly competent physicians who are responsible for diagnosis and treatment of the pediatric patient, including some pediatric cardiologists, may not be aware that they have not yet become experts at auscultation. The skill of auscultation of the heart must be learned by supervised experience with patients in whom a wide variety of normal and abnormal heart sounds and murmurs can be heard. Once learned, the skill can be maintained only by frequent practice in hearing and evaluating both subtle and obvious sounds emanating from the heart and from the pulmonary and systemic blood vessels. PMID- 2308790 TI - Caring in nursing education: a theoretical blueprint. PMID- 2308792 TI - Make room for care: challenges for faculty of undergraduate nursing curricula. PMID- 2308791 TI - The experience of caring in the teaching-learning process of nursing education: student and teacher perspectives. PMID- 2308793 TI - Knowing care in the clinical field context: an educator's point of view. PMID- 2308794 TI - The marginal. PMID- 2308795 TI - Creative strategies for teaching care. PMID- 2308796 TI - Teaching care as the essence of nursing administration. AB - Not all nurses in managerial positions care for their clients (nursing departments). It is imperative that nurses in managerial positions implement strategies that will enable all nurses to value care. By focusing a nursing management curriculum on care, nurse-managers will value care and incorporate care into their nursing departments. "Health care delivery systems of this nation are currently dominated by an industrial management model. . . . Such a model presents serious conflict with a care culture and nursing, having mastered the current management model, must now move to merge it with the essentials of a care culture. Only then will we create new nursing models which will be responsive to the health care needs of the 21st century". PMID- 2308797 TI - Virtue, ethics, and care: developing the personal dimension of caring in nursing education. PMID- 2308798 TI - Theoretical directives for care value conflict resolution. PMID- 2308799 TI - Using the arts in clinical practice. PMID- 2308800 TI - Deciding to care: a way to knowledge. PMID- 2308801 TI - A caring community. PMID- 2308802 TI - Using photography with families of chronically ill children. PMID- 2308803 TI - The moral dimension: humanism in education. PMID- 2308804 TI - Creating a caring environment: moral obligations in the role of dean. AB - Mayeroff (1971) states "from a loose stringing together of ideas a tight fabric emerges; ideas intertwine and tend to reinforce each other, making for a mutual deepening of meaning and gain in precision". The fabric throughout this discussion is nursing. Commitment, compassion, confidence, competence, and conscience represent the ideas that, when uniquely and beautifully woven together, create the aesthetic experience of caring in nursing. The dean of a caring-based nursing program is morally obligated to foster an environment that reflects a commitment to caring. PMID- 2308805 TI - Caring as the central focus in nursing curriculum development. AB - Nursing literature and conferences are advocating a return to the humanistic values and caring approach to people that has been a hallmark of nursing. A theory base for caring in nursing is emerging. Over the past 10 years several research studies in nursing have focused on the concept of caring. Most studies have dealt with defining and understanding the concept of caring and identifying attributes of caring from the perspective of the patient/client and from that of the nurse. New work on caring is looking at teaching of the concept in schools of nursing (Bauer, 1988), the economics of caring (Buerhaus, 1986), the relationship between caring and nurse burnout (Gustafson, 1984), issues of ethics and caring (Fry, 1988 & 1989), to name just a few. The concept of caring is being legitimized as an area appropriate for nurses to study. As nursing educators know, building a program on a strong philosophical base with faculty committed to implementation of the program philosophy is crucial for success of program outcome. Using a caring framework for teaching nursing exposes nursing students to more than an empirical basis for practice. An holistic approach to really understanding people as human beings of value, worth, and having needs becomes the focus of content. To effectively teach caring, faculty must role model the attributes of caring to nursing students. This involves accepting and treating students as having value, worth, and the potential for growth. Faculty must also feel good about themselves and their abilities as teachers. Faculty need to feel confident and comfortable in their role as educators, master their subject matter, and be willing to get involved with students. Faculty development programs, recruitment of faculty espousing a caring philosophy, and mentoring new faculty into their modeling role are important considerations for the effective teaching of caring. Promoting a caring framework for nursing and faculty modeling of caring behaviors and attitudes could affect student recruitment. In our highly technologic society, great emphasis is being placed on person-to-person relationships. Reaffirming the caring nature of nursing to the public and actively promoting these behaviors may make the nursing profession a more attractive and appealing career choice. PMID- 2308806 TI - Phenomenology of self: an experiential approach to the teaching and learning of caring. PMID- 2308807 TI - Learning caring behavior in an integrated manner. AB - We can see that by transferring caring behaviors from previous experiences, by imitation of role models, and by multiple experiential activities, learners form and utilize schemata of caring. By finding ways to stimulate learners to think about the feeling of caring and to imagine caring for others, caring becomes a psychophysiological or psychokinesthetic experience. A broad aim or high-level purpose, that is, to care, to have interest in and concern for others, or union and separation toward growth could serve as an inner context that would automatically evoke associated networks of learned, integrated caring actions. The caregiver would not usually be aware of each separate action. These broad aims would organize procedural knowledge, or "know how," in the motor areas of the brain. Let us return to Gardield's predicament. Can we help him walk again? Perhaps someone will call him in a friendly voice, someone whom he knows will give him a little chow and lots of stroking on his head. I suspect he would forget about his feet and just hurry over. PMID- 2308808 TI - The lived experience of nursing education: a phenomenological study. PMID- 2308809 TI - The tensions and passions of caring. PMID- 2308810 TI - Toward a theory of professional nursing caring: a unifying perspective. AB - This paradigm of professional nursing caring unifies aspects of humanistic and scientific perspectives. Through interconnections of the holistic nursing perspective, person-environment interactions, and the caring ethic, fusion occurs that reorganizes old orders and structures. From this dynamic, creative energies are generated and used in being, relating, and acting by the nurse through therapeutic use of self. Through professional nursing caring, the wholeness and integrity of a patient-client is maintained and assisted toward actualization, with wellness and illness outcomes altered, and more caring health-related environments restructured that preserve and support the humanness of patients and people in those environments. The professional nursing paradigm has been guided in organization by a holographic perspective of reality, a perspective that envisions two realms: the implicate and the explicate, with the implicate available to the explicate realm in dealing with reality. The two realities have been unified into a holonomic order in which the essences (qualities) and entities (actions) of professional nursing caring have been restructured into a new order. The paradigm opens avenues for constructing a nursing theory in which caring is systematically embedded in concepts, structure, and relations. The imperative for nursing education is to reconceptualize professional nursing caring and undertake the effort and energy required to place this essence in the heart of nursing theory, practice, education, and research. This is the profession's challenge for the coming decade. PMID- 2308811 TI - Dependent and authentic care: implications of Heidegger for nursing care. PMID- 2308812 TI - Nursing education as authentic nursing care. PMID- 2308813 TI - Serendipity. PMID- 2308814 TI - The meaning of human care and the experience of caring in a university school of nursing. PMID- 2308815 TI - The essential structure of a caring and an uncaring encounter with a teacher: the perspective of the nursing student. PMID- 2308816 TI - Point mutation analysis of the Xenopus laevis RNA polymerase I core promoter. AB - The core region of the Xenopus laevis pre-ribosomal RNA promoter was subjected to point mutation analysis. A total of 27 point mutants within a 78 base pair region from -64 to +14, (relative to the start of transcription at +1), were assayed by oocyte microinjection. The results locate the 3' boundary of the core promoter at +4 and the 5' boundary at between -33 and -39 and suggest that this region of the Xenopus promoter is generally similar in organisation to mammalian core promoters. In particular, the conserved guanidine nucleotides at -7 and -16 are clearly essential for promoter function. The data suggest that interactions between the transcription machinery and the promoter occur in four distinct regions around +2 to +4, -7, -17 to -20 and -28 to -33. This particular periodicity of functionally important nucleotides is consistent with a model in which all protein-DNA interactions take place from predominantly one side of the DNA helix. PMID- 2308817 TI - A functional splice site in the 5' untranslated region of a zein gene. AB - Zein genes, the genes coding for the zein storage proteins of maize, have a unique gene structure where at least two promoters lie upstream of the coding region. Between the P1 promoter (900 base pairs upstream of the coding region) and the translation initiation AUG codon are 18 short reading frames. A discrepancy between the signals obtained by S1-mapping and primer extension and the DNA sequence in the region of one of these signals suggests the presence of a 3' splice site lying 40 nucleotides upstream of the coding region. A splicing event removing all of the short reading frames from the mRNA transcribed from the P1 promoter would bring this mRNA into a translatable form. Further evidence for a functional 3' splice site has been obtained from sequencing of primer extension products and in vitro splicing of a hybrid intron in the HeLa cell in vitro splicing system. PMID- 2308818 TI - Analysis of the rearrangements associated with carcinogen-induced activation of the hamster thymidine kinase gene. AB - We have previously shown that chemical carcinogen treatment of RJK92 hamster cells activates the quiescent thymidine kinase (TK) gene and that 20% of the TK+ variants have a rearrangement in the region 5' to the TK gene (Barr et al. (1986) Mol. Cell. Biol. 6, 3023-3033). After cloning the wild type 5' region to obtain detailed mapping data and hybridization probes, we localized the rearrangement breakpoints by Southern blot analysis to a 1.5 kb region 6 kb 5' to the origin of transcription. This analysis also demonstrated that the rearrangements consist at least partly of a deletion of wild type sequences 5' to this breakpoint region. The region near the transcription origin in the rearranged TK genes has a DNase I sensitive chromatin conformation and a DNase I hypersensitive site as well as the previously described domain of demethylation (Ibid.). Though this domain of demethylation extends into the breakpoint region, the rearranged region is not associated with DNase I sensitivity nor hypersensitive sites. The rearrangement also does not detectably alter the growth-related regulation of TK activity in these cells. PMID- 2308819 TI - Purification to apparent homogeneity and partial amino acid sequence of rat liver O6-alkylguanine-DNA-alkyltransferase. AB - O6-alkylguanine-DNA-alkyltransferase (ATase) activity was increased in rat liver from 80 to 320 fmoles/mg total protein 48 h after administration of 2 acetylaminofluorene at 60 mg/kg body weight. This tissue was used as a source of ATase which was purified by ammonium sulphate precipitation and DNA-cellulose, molecular exclusion and ion exchange chromatography (IEC). IEC purified material showed a major 24 kDa band after polyacrylamide gel electrophoresis (PAGE) with silver staining. Fluorography of purified ATase following incubation with [3H] methylated substrate DNA and PAGE showed a single band at 24 kDa suggesting that, as with bacterial ATases, the protein itself accepts the alkyl group from O6 alkylguanine in substrate DNA during the repair reaction. Further purification of the protein using reverse phase HPLC resulted in a single peak representing approximately 125,000 fold purification. This was subjected to amino-terminal sequencing and it was found that the protein was blocked at the amino-terminal end: it was cleaved using trypsin or cyanogen bromide and the amino acid sequence of several reverse phase HPLC purified fragments was determined. PMID- 2308820 TI - Splicing of a C. elegans myosin pre-mRNA in a human nuclear extract. AB - Splicing of mammalian introns requires that the intron possess at least 80 nucleotides. This length requirement presumably reflects the constraints of accommodating multiple snRNPs simultaneously in the same intron. In the free living nematode, C. elegans, introns typically are 45 to 55 nucleotides in length. In this report, we determine whether C. elegans introns can obviate the mammalian length requirement by virtue of their structure or sequence. We demonstrate that a 53 nucleotide intron from the unc-54 gene of C. elegans does not undergo splicing in a mammalian (HeLa) nuclear extract. However, insertion of 31 nucleotides of foreign, prokaryotic sequence into the same intron results in efficient splicing. The observed splicing proceeds by the same two-step mechanism observed with mammalian introns, and exploits the same 3' and 5' splice sites as are used in C. elegans. The branch point used lies in the inserted sequence. We conclude that C. elegans splicing components are either fewer in number or smaller than their mammalian counterparts. PMID- 2308821 TI - Site-specific inhibition of EcoRI restriction/modification enzymes by a DNA triple helix. AB - The ability of oligopyrimidines to inhibit, through triple helix formation, the specific protein-DNA interactions of the EcoRI restriction and modification enzymes (EcoRI and MEcoRI) with their recognition sequence (GAATTC) was studied. The oligonucleotides (CTT)4 and (CTT)8 formed triplexes in plasmids at (GAA)n repeats containing EcoRI sites. Cleavage and methylation of EcoRI sites within these sequences were specifically inhibited by the oligonucleotides, whereas an EcoRI site adjacent to a (GAA)n sequence was inhibited much less. Also, other EcoRI sites within the plasmid, or in exogenously added lambda DNA, were not inhibited. These results demonstrate the potential of using triplex-forming oligonucleotides to block protein-DNA interactions at specific sites, and thus this technique may be useful in chromosome mapping and in the modulation of gene expression. PMID- 2308822 TI - Active site amino acid sequence of the bovine O6-methylguanine-DNA methyltransferase. AB - An O6-methylguanine-DNA methyltransferase has been partially purified from calf thymus by conventional biochemical techniques. The enzyme was specifically radioactively labelled at the cysteine residue of the active site and further purified by attachment to a solid support. Following digestion with trypsin, a radioactive peptide containing the active site region of the protein was purified by size fractionation, ion exchange chromatography and reverse phase HPLC. The technique yielded an essentially homogeneous oligopeptide which was subjected to amino acid sequencing. The sequence adjacent to the acceptor cysteine residue of the bovine protein exhibits striking homology to the C-terminal methyl acceptor site of the E. coli Ada protein and the proposed acceptor sites of the E. coli Ogt and the B. subtilis Dat1 proteins. PMID- 2308824 TI - The nucleotide sequence of pathogenesis-related (PR) 1b protein gene of tobacco. PMID- 2308823 TI - Nucleotide sequence of the mitochondrial genome of Paramecium. AB - The nucleotide sequence for 40,469 bp of the linear Paramecium aurelia mitochondrial (mt) genome is presented with the locations of the known genes, presumed ORFs, and their transcripts. Many of the genes commonly encoded in mt DNA of other organisms have been identified in the Paramecium mt genome but several unusual genes have been found. Ribosomal protein genes rps14, rps12, and rpl2 are clustered in a region that also contains two other genes usually found in chloroplasts, but rpl14 is over 16 kbp away. The ATP synthase gene, atp9, is encoded in this mt genome, but the atp6, atp8, and COIII genes have not been identified. All of the identified genes are transcribed. Many mono- and poly- cistronic transcripts have been detected which cover most of the genome, including large regions where genes have yet to be identified. Based on sequence comparisons with known tRNAs, only those for phe, trp, and tyr are encoded in Paramecium mt DNA. PMID- 2308825 TI - The nucleotide sequence of pathogenesis-related (PR) 1c protein gene of tobacco. PMID- 2308826 TI - Nucleotide sequence of the chloroplast rbcL gene from cotton Gossypium hirsutum. PMID- 2308827 TI - Nucleotide sequence of the Zymomonas mobilis alcohol dehydrogenase II gene. PMID- 2308828 TI - Alternative splicing in the human cytochrome P450IIB6 gene: use of a cryptic exon within intron 3 and splice acceptor site within exon 4. PMID- 2308829 TI - Novel short interspersed repeat in human DNA. PMID- 2308830 TI - The TTV1-encoded viral protein TPX: primary structure of the gene and the protein. PMID- 2308831 TI - Nucleotide sequence of the infectious cloned DNA components of African cassava mosaic virus (Nigerian strain). PMID- 2308832 TI - Primary structure of guinea pig apolipoprotein E. PMID- 2308833 TI - A simple discontinuous buffer system for increased resolution and speed in gel electrophoretic analysis of DNA sequence. PMID- 2308835 TI - New synthetic routes to protected purine 2'-O-methylriboside-3'-O phosphoramidites using a novel alkylation procedure. AB - A highly selective alkylation procedure has been developed enabling new synthetic routes to be established for protected purine 2'-O-methylriboside-3'-O phosphoramidites; building blocks for the assembly of 2'-O methyloligoribonucleotides. The new procedure avoids the use of the highly toxic and potentially explosive reagent diazomethane and is far superior to the use of silver oxide/methyl iodide. Moreover, the use of highly versatile key intermediates will enable the synthesis of a wide variety of base modified analogues as well as other 2'-O-alkylriboside derivatives. PMID- 2308834 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2308836 TI - Nuclear factor-I and activator protein-2 bind in a mutually exclusive way to overlapping promoter sequences and trans-activate the human growth hormone gene. AB - Transcription of the human growth hormone (hGH) gene and its regulation are controlled by trans-acting factors that bind to hGH gene promoter sequences. Several DNase I footprints have been described within 500 bp of this promoter, one of which (-289 to -267) has not yet been ascribed to a defined factor. By DNase I footprinting, gel mobility shift, and methylation interference assays with extracts from HeLa cells and GH-producing pituitary tumor (GC) cells, we show that this factor belongs to the NF-I family. When NF-I was competed out of the cell extracts, the trans-acting factor AP-2 bound to the same site as NF-I. AP-2 was present not only in HeLa cells, but also in GC cells albeit at a much lower concentration. Consistent with the mutually exclusive binding of NF-I and AP-2, their methylation interference patterns included four guanine residues that were crucial for binding of both NF-I and AP-2. Cell-free transcription from the hGH gene promoter showed that these two factors can transactivate this gene. PMID- 2308837 TI - Chloroplast genes transferred to the nuclear plant genome have adjusted to nuclear base composition and codon usage. AB - During plant evolution, some plastid genes have been moved to the nuclear genome. These transferred genes are now correctly expressed in the nucleus, their products being transported into the chloroplast. We compared the base compositions, the distributions of some dinucleotides and codon usages of transferred, nuclear and chloroplast genes in two dicots and two monocots plant species. Our results indicate that transferred genes have adjusted to nuclear base composition and codon usage, being now more similar to the nuclear genes than to the chloroplast ones in every species analyzed. PMID- 2308838 TI - In vitro suppression of an amber mutation by a chemically aminoacylated transfer RNA prepared by runoff transcription. AB - An amber suppressor tRNA was prepared in vitro by runoff transcription with T7 RNA polymerase. Both full-length tRNA and truncated tRNA lacking the 3' terminal pCpA from the acceptor stem could be synthesized from the same DNA template. Truncated runoff suppressor tRNA could be enzymatically ligated to phenylalanyl pCpA to generate aminoacylated full-length suppressor tRNA (Phe-tRNA(CUA)). Phe tRNA(CUA) is capable of suppressing an amber (UAG) mutation in vitro with equivalent efficiency as suppressor prepared by anticodon-loop replacement of a naturally-isolated tRNA. The ease of suppressor tRNA preparation using this method, compared to anticodon-loop replacement, greatly facilitates the use of chemically acylated suppressor tRNA's for site-specifically incorporating unnatural amino acids into proteins. PMID- 2308839 TI - Structure and transcription of a human gene for H1 RNA, the RNA component of human RNase P. AB - The gene coding for H1 RNA, the RNA component of human RNase P, has been isolated and characterized from a human genomic DNA library. The sequence corresponding to the mature H1 RNA is almost identical to that previously identified using H1 RNA and a cDNA clone corresponding to it. The nucleotide sequence of the genomic clone contains an array of potential transcriptional control elements, some characteristic of transcription by RNA polymerase III and some characteristic of RNA polymerase II, as is also the case for U6 and certain other small stable RNAs. The transcription in vitro of the genomic clone shows that the gene is functional and is transcribed by RNA polymerase III. Southern hybridization analysis indicates that there is very likely only one copy of the gene for H1 RNA in the human genome. PMID- 2308840 TI - Organization of the 3'-boundary of the chicken alpha globin gene domain and characterization of a CR 1-specific protein binding site. AB - The sequence of a DNA fragment about 1 Kbp long located at the 3' boundary of the chicken alpha globin gene domain, including the 3'-side matrix attachment point and the site of transcription termination, was determined. It contains a repetitive DNA element and the AT-rich (easily denaturable) DNA segment conserved at the same position in the duck genome. The repetitive sequence was identified by computer analysis as being a member of the CR1 family. Within the non repetitive part of the AT-rich DNA fragment, four topoisomerase II recognition sites were found which might be indicative of matrix attachment. Furthermore, two distinct regions were identified, possessing strong homology to a number of noncoding consensus sequences, one of them to a limited part of the LTR of HTLVIII, and the other to the replication origin of Polyoma virus JC. DNA shift experiments showed that the CR1 repeat binds specifically an abundant nuclear protein factor. The binding site for this factor was identified by footprinting and turned out to be closely related to the previously described recognition site for the TGGCA-binding protein, the chicken analog of nuclear factor 1 (NF-1). Finally, the CR1 repeats within the chicken alpha and beta globin gene domains were mapped. All these observations are discussed in terms of the organization of the 5' and 3' boundaries of the functional genomic domains forming a chromatin loop including all avian alpha type globin genes. PMID- 2308842 TI - The residual repair capacity of xeroderma pigmentosum complementation group C fibroblasts is highly specific for transcriptionally active DNA. AB - We have measured removal of pyrimidine dimers in defined DNA sequences in confluent and actively growing normal human and xeroderma pigmentosum complementation group C (XP-C) fibroblasts exposed to 10 J/m2 UV-irradiation. In normal fibroblasts 45% and 90% of the dimers are removed from the transcriptionally active adenosine deaminase (ADA) gene within 4 and 24 hours after irradiation respectively. Equal repair efficiencies are found in fragments located entirely within the transcription unit or partly in the 3' flanking region of the ADA gene. The rate and extent of dimer removal from the dihydrofolate reductase (DHFR) gene is very similar to that of the ADA gene. Repair of the transcriptionally inactive 754 locus is less efficient: 18% and 52% of the dimers are removed within 4 and 24 hours respectively. In spite of the limited overall repair capacity, confluent XP-C fibroblasts efficiently remove dimers from the ADA and DHFR genes: about 90% and 50% within 24 hours respectively. The 3' end of the ADA gene is repaired as efficiently as in normal human fibroblasts, but less efficient repair occurs in DNA fragments located in the DHFR gene and at the 5' end of the ADA gene. Repair of the inactive 754 locus does not exceed the very slow rate of dimer removal from the genome overall. Confluent and actively growing XP-C cells show similar efficiencies of repair of the ADA, DHFR and 754 genes. Our findings suggest the existence of two independently operating pathways directed towards repair of pyrimidine dimers in either active or inactive chromatin. XP-C cells have lost the capacity to repair inactive chromatin, but are still able to repair active chromatin. PMID- 2308841 TI - Organization of the mitochondrial genome of Atlantic cod, Gadus morhua. AB - The mitochondrial DNA (mtDNA) from the Atlantic cod, Gadus morhua, was mapped using 11 different restriction enzymes and cloned into plasmid vectors. Sequence data obtained from more than 10 kilobases of cod mtDNA show that the genome organization, genetic code, and the overall codon usage have been conserved throughout the evolution of vertebrates. Comparison of the derived amino acid sequences of proteins encoded by cod mtDNA to the ones encoded by Xenopus laevis mtDNA revealed that the amino acid identity range from 46% to 93% for the different proteins. ND4L is most divergent while COI is most conserved. GUG was found as the translation initiation codon of the COI gene, indicating a dual coding function for this codon. The sequences of the 997 base pair displacement loop (D-loop)-containing region and the origin of L-strand replication (oriL), are presented. Only few of the primary and secondary structure features found to be conserved among mammalian mitochondrial D-loops, can be identified in cod. Presence of CSB-2 in the D-loop-containing region and the conserved hairpin structure at oriL, indicates that replication of bony fish mtDNA may follow the same general scheme as described for higher vertebrates. PMID- 2308843 TI - The synthesis of polyamide-oligonucleotide conjugate molecules. AB - We have developed methods for the synthesis of peptide-oligodeoxyribonucleotide conjugate molecules in particular, and polyamide-oligonucleotide conjugates in general. Synthesis is carried out by a solid-phase procedure and involves the assembly of a polyamide on the solid support, conversion of the terminal amino group to a protected primary aliphatic hydroxy group by reaction with alpha, omega-hydroxycarboxylic acid derivatives, and finally oligonucleotide synthesis using phosphoramidite chemistry. The conjugate molecules can be used as DNA probes, with the polyamide component carrying one or more non-radioactive markers. These conjugates also have the potential to be used as anti-sense inhibitors of gene expression, with the peptide segment acting as a targeting moiety. PMID- 2308844 TI - RNA dependent RNA polymerase activity associated with the double-stranded RNA virus of Giardia lamblia. AB - Giardia lamblia, a parasitic protozoan, can contain a double-stranded RNA (dsRNA) virus, GLV (1). We have identified an RNA polymerase activity present specifically in cultures of GLV infected cells. This RNA polymerase activity is present in crude whole cell lysates as well as in lysates from GLV particles purified from the culture medium. The RNA polymerase has many characteristics common to other RNA polymerases (e.g. it requires divalent cations and all four ribonucleoside triphosphates), yet it is not inhibited by RNA polymerase inhibitors such as alpha-amanitin or rifampicin. The RNA polymerase activity synthesizes RNAs corresponding to one strand of the GLV genome, although under the present experimental conditions, the RNA products of the reaction are not full length viral RNAs. The in vitro products of the RNA polymerase reaction co sediment through sucrose gradients with viral particles; and purified GLV viral particles have RNA polymerase activity. The RNA polymerase activities within and outside of infected cells closely parallel the amount of virus present during the course of viral infection. The similarities between the RNA polymerase of GLV and the polymerase associated with the dsRNA virus system of yeast are discussed. PMID- 2308845 TI - Recombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNA. AB - Large-scale deletions of mitochondrial DNA (mtDNA) have been described in patients with progressive external ophthalmoplegia (PEO) and ragged red fibers. We have determined the exact deletion breakpoint in 28 cases with PEO, including 12 patients already shown to harbor an identical deletion; the other patients had 16 different deletions. The deletions fell into two classes. In Class I (9 deletions; 71% of the patients), the deletion was flanked by perfect direct repeats, located (in normal mtDNA) at the edges of the deletion. In Class II (8 deletions; 29% of patients), the deletions were not flanked by any obviously unique repeat element, or they were flanked by repeat elements which were located imprecisely relative to the breakpoints. Computer analysis showed a correlation between the location of the deletion breakpoints and sequences in human mtDNA similar to the target sequence for Drosophila topoisomerase II. It is not known how these deletions originate, but both slipped mispairing and legitimate recombination could be mechanisms playing a major role in the generation of the large mtDNA deletions found in PEO. PMID- 2308846 TI - B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)3X4(CG)3] (X = A, T, G, C). AB - Circular Dichroism (CD) spectra were collected as a function of sodium perchlorate concentration [NaClO4] for the set of DNA hairpins formed from the oligomer sequences d[(CG)3X4(CG)3] where X = A, T, G or C. Over the range in salt concentration from 0 to 4.0 M NaClO4, the CD spectra invert in a manner characteristic of the B to Z transition. A factor analysis routine is described and employed to determine the least number of basis spectra required to fit the measured spectra of each hairpin over the entire salt range examined. In every case, linear combinations of only two sub-spectra fit the experimental spectra of the hairpins with greater than 98% accuracy, indicating the spectrally monitored structural transitions are two-state. From the relative weights of the individual sub-spectra, B-Z transition curves are constructed. The transitions are analyzed in terms of a simple two-state equilibrium model which yields an evaluation of the transition free-energy, delta GB-Z, as a function of NaClO4 concentration. At 1.0 M NaClO4 and 21 degrees C, delta GB-Z = 5.4, 4.9, 3.6 and 2.3 kcal/mole for the G4, T4, A4 and C4 loop hairpins, respectively. PMID- 2308847 TI - A new model for the bending of DNAs containing the oligo(dA) tracts based on NMR observations. AB - The conformations of double-stranded d(GGAAATTTCC) x 2, d(GGTTTAAACC) x 2, d(CGCAAAAAAGCG)d(CGCTTTTTTGCG) and d(GCATTTTGAAACG)d(CGTTTCAAAATGC) have been studied by NMR spectroscopy. Analyses of cross peaks in NOESY spectra between the H2 of an adenine and the H1' of a deoxyribose in the 3'-neighbouring residue on the complementary strand revealed that the minor groove of the oligo(dA) tract is compressed gradually from 5' to 3' in each duplex. In view of this gradual compression of the minor groove along the oligo(dA) tract, it can be understood clearly why d(GGAAATTTCC)n x 2 and d(GAAAATTTTC)n x 2 are bent, and d(GGTTTAAACC)n x 2 and d(GTTTTAAAAC)n x 2 are not bent. The relative extents of bending of a series of d(AjN10-j)nd(N10-jTj)n sequences can also be understood systematically. Additionally, it was found that the TA step disturbed the compression of the minor groove of the oligo(dA) tract to some extent. PMID- 2308848 TI - Detection of a novel minisatellite-specific DNA-binding protein. AB - We describe the detection of a ubiquitous DNA-binding protein which appears to interact specifically with tandem-repeated minisatellites. The murine 40 kd protein, which we term Msbp-1, was found to be present in all mouse tissues tested. This protein was bound specifically and with high affinity by double stranded DNA containing a repeat sequence related to the minisatellite 'core' sequence, and binding required the presence of multiple repeat units. Corresponding minisatellite-specific DNA-binding proteins could also be detected in species ranging from Drosophila to man. This analysis represents the first direct evidence that minisatellites can function as a specific recognition signal for an endogenous DNA-binding protein. PMID- 2308849 TI - Nucleotide sequence of the PA gene of influenza A/WSN/33(H1N1). PMID- 2308850 TI - Nucleotide sequence of an A-type legumin gene from pea. PMID- 2308851 TI - Complete cDNA sequence of sorghum phosphoenolpyruvate carboxylase involved in C4 photosynthesis. PMID- 2308852 TI - Nucleotide sequence of the isopenicillin N synthase gene (pcbC) of the gram negative Flavobacterium sp. SC 12,154. PMID- 2308853 TI - Nucleotide and derived amino acid sequence of rps2 from maize chloroplasts. PMID- 2308854 TI - The primary structure of 5S ribosomal RNAs from Magnolia cobus and Magnolia stellata. PMID- 2308855 TI - Sequence of cbh-1 gene of Humicola grisea var. thermoidea. PMID- 2308856 TI - Nucleotide sequence of a novel transcript confined in HeLa cell nucleus. PMID- 2308857 TI - Nucleotide sequence of the alternatively spliced human thyroid peroxidase cDNA, TPO-2. PMID- 2308858 TI - Nucleotide sequence of the bovine insulin-like growth factor 1 (IGF-1) and its IGF-1A precursor. PMID- 2308859 TI - Sequence of the cDNA encoding ITF-1, a positive-acting transcription factor. PMID- 2308860 TI - Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor. PMID- 2308861 TI - Nucleotide sequence of a cDNA clone of Xenopus platelet-derived growth factor A chain. PMID- 2308862 TI - Human cDNA sequence homologous to the mouse LLRep3 gene family. PMID- 2308863 TI - Nucleotide sequence of a cloned rice genomic DNA fragment that encodes a 10 kDa prolamin polypeptide. PMID- 2308864 TI - The sequence of an adrenal specific human cDNA, pG2. PMID- 2308865 TI - A new type II restriction endonuclease, BsmA I, from Bacillus stearothermophilus. PMID- 2308866 TI - Transformation of Schizosaccharomyces pombe by electroporation. PMID- 2308867 TI - An anonymous DNA probe E20 [D4S143] on chromosome 4 detects a TaqI polymorphism. PMID- 2308869 TI - Correlations of dietary intake and blood nutrient levels with esophageal cancer mortality in China. AB - Using dietary, blood nutrient, and esophageal cancer mortality data from 65 Chinese counties, we examined several correlations to help provide clues to the influence of diet and nutrition on the geographic variation of esophageal cancer in China. Esophageal cancer mortality was significantly inversely related to reported fruit consumption and to plasma ascorbic acid concentration. The age adjusted mortality rates were more than three times higher for counties in the lowest compared with the highest quartile of fruit intake or plasma vitamin C. Positive correlations with intake of moldy vegetables were observed but not with tobacco and alcohol consumption. There were suggestive inverse associations with blood selenium and riboflavin but little effect of fat-soluble vitamins. Limitations of ecological data preclude causal inferences, but the relationships provide leads to dietary factors that may contribute to the exceptionally high rates of esophageal cancer in several areas of China. PMID- 2308868 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2308870 TI - Reproducibility of a diet history in older men in Hawaii. AB - A diet history method was tested for reproducibility among 106 older men from the five major ethnic groups (Japanese, Caucasian, Hawaiian, Filipino, and Chinese) of Hawaii. The questionnaire, administered by trained interviewers, was designed to estimate the dietary intakes of total and saturated fat, cholesterol, vitamin A, beta-carotene, vitamin C, and zinc. Subjects were asked to recall their usual frequencies and amounts of consumption during a usual month of more than 100 food items, along with the intake of seasonal foods with a high vitamin A content. A second interview was conducted 1-14 months later to obtain a diet history covering the same time period as the first interview. The same questionnaire was utilized in both interviews. The effects of ethnicity, age, and recall interval (period between the diet reference date and initial interview) on the reproducibility of nutrient intakes were examined. The intraclass correlation coefficient (rI) and the weighted kappa statistic (Kw) were used to assess agreement. The overall levels of reproducibility were relatively good. Neither ethnicity, age, nor length of recall period had a major effect on reproducibility. The data suggested that this diet history method is an appropriate instrument for estimating the usual dietary intakes of a healthy heterogeneous group of older men in Hawaii. PMID- 2308871 TI - Effects of dietary fat and protein on DMH-induced tumor development and immune responses. AB - Although in three different mouse tumor systems with corn oil as dietary fat we previously found that milk protein decreased tumor development compared with beef, the results were reversed in 1,2-dimethylhydrazine (DMH)-injected mice. The purpose of this study was to determine if the latter result was due to the protein source. BALB/c mice (n = 280) were divided into five diet groups and injected 10 times at weekly intervals with DMH (20 mg/kg wt) or saline. Four diets contained 11% protein (casein, milk, or beef) and 5% fat (corn oil or beef tallow), and the AIN-76A diet was used as a control diet. The source of fat was a significant modulator of tumor development. Corn oil markedly increased total tumor volume and the number of tumors per mouse compared with beef tallow. Its tumor-enhancing effects were evident when it was combined with milk but not with casein. In addition, significantly lower lymphoproliferation and T-cell cytotoxicity against colon tumor cell targets was associated with corn oil consumption, whereas nonfat milk as the protein source was related to normal oxidative burst capacity of phagocytes. These results demonstrate that the source of dietary fat, in addition to the protein source, has a profound effect on both tumor development and immune responsiveness in this animal tumor system. PMID- 2308872 TI - The influence of pre- and postnatal caloric intake on colon carcinogenesis. AB - Mother rats were allowed to litter under conventional conditions. They were fed a complete, semipurified diet during gestation, and at time of littering the numbers of pups were reduced to either eight per litter or four per litter in two additional groups. At weaning, all rats were continued on the same diet that their mothers had consumed. One group of those reduced to four per litter at birth was allowed to continue to eat ad libitum while the other group, reduced to four per litter, was pair fed to the ad libitum eight per litter group. The group reduced to four per litter at birth and allowed to eat ad libitum during postnatal life gained the most weight and were heaviest at the termination of the study. This group also had the greater incidence and frequency of colon tumors when exposed to dimethylhydrazine (DMH). The group pair fed to rats fed conventional diets, eight rats per litter, had an incidence and frequency of tumors between the other two groups. These data demonstrate that early exposure to excess calories increased risk for cancer and that early and late excess caloric intake further increased risk. Thus, pre- and perinatal caloric intake may have a significant influence on susceptibility to cancer later in life. Mechanisms are only speculative but may include differences in metabolism and modulation of hormonal balance. PMID- 2308873 TI - Husband-wife diet concordance and changes in dietary practices by surviving spouses of cancer cases. AB - Diet concordance and changes in dietary practices by surviving spouses of cancer cases were investigated by studying 69 husband-wife pairs during an eight-year period spanning the death from cancer of one spouse. The data base consisted of reports for each cancer case from the Adventist Health Study (AHS) where a surviving spouse was available. Two questions were addressed. 1. Do husbands and wives eat similar diets? 2. Did survivors change their diet practices during the eight-year period? Three sets of dietary data were compared with the AHS food frequency questionnaire: reports made in 1976 by cases; reports made in 1976 by their spouses (initial); and the spouses' reports in 1984 (current). Diet concordance and dietary changes for 35 key food groups were evaluated both for individual foods and across foods by computing recall scores. The results were analyzed with univariate and multivariate methods. Comparison of means and Spearman rank-order correlations revealed good initial concordance between the spouses, which was not significantly related to age, sex, or education. However, eight years later subsequent to the deaths of the cases, the agreement was poor because the surviving spouses had changed their diets. The changes in dietary practices were significantly related to education and body mass index in univariate analysis but not in analysis of covariance. These results indicate that retrospective recall by spouses for the cases rather than the spouses' own current reports should be used as an estimate for the deceased cases. Repeated recalls are necessary to increase reliability. PMID- 2308874 TI - Changes in intestinal function of rats initiated with DMH and fed varying levels of butterfat, calcium, and magnesium. AB - The effects of dietary calcium, magnesium, and butterfat on intestinal function and flora in rats initiated with 1,2-dimethylhydrazine (DMH) were studied. Male weanling rats were assigned to six isocaloric diets that varied in their levels of calcium and magnesium (0.25% Ca with 0.05% Mg, 1.0% Ca with 0.05% Mg, or 0.625% Ca with 0.50% Mg) and butterfat (5% or 20%). One-half of the rats in each treatment were injected subcutaneously with DMH weekly for four weeks. This short term exposure to DMH increased colonic ornithine decarboxylase (ODC) activity and the mass of cecal contents. Ingestion of the high levels of either calcium or magnesium depressed colonic ODC activity and depressed apparent absorption of organic matter, calcium, magnesium, and phosphorus. Ingestion of excess magnesium increased the mass of the cecal contents by twofold, caused hypertrophy of cecal walls, and increased the total amount of protein and total nitroreductase and beta-glucuronidase activity in the ceca of rats. Ingestion of supplemental calcium had less dramatic effects and increased the mass of cecal contents by only 28% and decreased the total amount of protein in the ceca. On the basis of their different effects on cecal microflora, magnesium appears to have less potential than does calcium as a protective agent against colon cancer. PMID- 2308875 TI - Chemoprotection of garlic extract toward cyclophosphamide toxicity in mice. AB - The effect of the administration of an extract of garlic (Allium sativum) was studied in mice that were treated with a chronic lethal dose of cyclophosphamide (50 mg/kg body wt, 14 days). The intraperitoneal administration of garlic (50 mg/animal, 14 days) along with cyclophosphamide reduced the toxicity of the latter considerably with an increase in life span of more than 70%. The administration of garlic extract did not improve the lymphopenia produced by cyclophosphamide or liver alkaline phosphatase, but there was a significant reduction in liver glutamic-pyruvic transaminase. Moreover, garlic extract reduced the level of lipid peroxidation induced in the liver by cyclophosphamide administration. Administration of garlic extract did not interfere with the tumor reducing activity of cyclophosphamide. PMID- 2308876 TI - The temporomandibular joint: the forgotten articulation. AB - Fifty-seven patients (79 temporomandibular joints) whose symptoms did not respond to conservative treatment subsequently underwent surgery to correct the internal derangement and obtain relief. This 8-year study emphasizes etiology, the diverse nature of the symptoms, clinical diagnosis, radiographic diagnostic features, surgical findings technique, postoperative treatment, complications, and long term results. Special attention is given to a heretofore undescribed bilaminar posterior ligament repair technique which appears to provide greater strength of repair and more natural joint function. PMID- 2308877 TI - A new technique for harvesting the patella tendon in patients undergoing anterior cruciate ligament reconstruction. AB - A new technique for harvesting the patella tendon for anterior cruciate ligament reconstruction is described. A circular oscillating saw is used to harvest the bone plugs. We feel that this technique offers reproducibility that is difficult to obtain with more conventional methods of graft harvesting. PMID- 2308878 TI - The use of magnetic resonance imaging in the diagnosis of pigmented villonodular synovitis. AB - Although the clinical and radiographic features of pigmented villonodular synovitis (PVS) have been well described, diagnosis is often delayed and high rates of recurrence after synovectomy are reported. Magnetic resonance imaging (MRI) has been shown to be useful in the diagnosis of soft tissue masses. Three patients with biopsy-proven PVS and radiographs showing only effusion underwent MRI in the axial, coronal, and sagittal planes. The margins of the diseased synovium were best demonstrated on long TR/TE (T2-weighted) images. The synovium contained areas of void signal intensity felt to be due to hemosiderin, interspersed with increased signal from both inflammation and fat. In all cases, the margins of the diseased synovium were clearly delineated, allowing classification as nodular or diffuse. No appreciable change in signal intensity was seen when comparing nodular and diffuse forms. MRI is useful but not specific for PVS, since rheumatoid synovitis may show a similar signal pattern. However, MRI in patients with suspected PVS may decrease the time until diagnosis, aid in preoperative planning and obtaining adequate margins of resection, and may be a non-invasive method of long-term follow up for possible recurrence. PMID- 2308879 TI - Correction of rotary malunion of the fingers by metacarpal rotational osteotomy. AB - Metacarpal rotational osteotomy was performed in 12 patients to correct rotary malunion following fractures of the phalanges and metacarpals. All but one patient obtained excellent correction of their preoperative deformities. The procedure is simple and gives predictable results. PMID- 2308880 TI - Overuse syndromes of the upper extremity in interpreters for the deaf. AB - Fourteen of 80 interpreters (18%) for deaf students at a national center on deafness sought medical care for painful conditions of the upper extremity; 11 others (14%) had less severe or transient symptoms. The conditions were brought on by repetitive use and were relieved by rest. All represented overuse syndromes. Tendinitis, fasciitis, synovitis, and nerve entrapment were encountered most often. Conservative treatment (eg, physical therapy, splinting, medications) was of little or no value. Only rest relieved symptoms. Surgery was rarely indicated. The most reasonable approach to treatment would, therefore, seem to be prevention. Suggested methods for avoidance of pain include limiting the duration of interpreting sessions, technique modification, and resistance exercises to increase endurance. PMID- 2308881 TI - Closed intramedullary pinning of metacarpal and phalanx fractures. AB - The surgical technique for closed intramedullary pinning of metacarpal and phalanx fractures is described. Commonly available 0.045 K-wires are used in a manner similar to Ender or Rush nailing of long bone fractures. This technique avoids impaling soft tissue structures--a drawback to more commonly used percutaneous K-wire techniques--and provides sufficient stability to allow early, protected motion. PMID- 2308882 TI - Closed versus open reduction of congenital hip dislocation in patients under 2 years of age. PMID- 2308883 TI - Anterior knee dislocation: case report and discussion. PMID- 2308884 TI - Diagnosis of oblique fractures of the distal ulna using an extended pronated view of the wrist. PMID- 2308885 TI - Cervical spondylolysis. PMID- 2308886 TI - Polymicrobic septic arthritis caused by Kingella kingae and enterococcus. PMID- 2308887 TI - Fulminant fat embolism. PMID- 2308888 TI - Literacy and the pediatrician. PMID- 2308889 TI - Point-counterpoint. PMID- 2308890 TI - Percolation theory and compactibility of binary powder systems. AB - Defined size fractions of polyethyleneglycol powder (MW = 10,000) were mixed with defined size fractions of alpha-lactose monohydrate in order to study the effect of compaction as a function of the weight ratios of the two excipients. For a precise control of the compression cycle, tablets were compressed on a Universal Testing Machine (Zwick 1478). Tablet tensile strength sigma T was quantified as a function of compressional stress sigma c and relative density rhor r using a two parameter model with sigma Tmax = maximal tensile strength at zero porosity and gamma = compressibility. The results have been analyzed on the basis of the percolation theory. As soon as the component with the lower mechanical stability is percolating the powder system, tablet hardness is controlled entirely by this component. The percolation threshold is a function of the geometrical arrangement of the particles in the compressed powder system. The expected two percolation thresholds can be distinguished as a function of the composition weight ratios if the particle size distributions of the two components differ enough. PMID- 2308891 TI - Transport mechanisms in iontophoresis. I. A theoretical model for the effect of electroosmotic flow on flux enhancement in transdermal iontophoresis. AB - Bulk fluid flow or volume flow in the direction of counterion flow is a probable mechanism for enhanced flux of uncharged species by iontophoresis. Both the electrical volume force effect, resulting from the interaction of the "ion atmosphere" and the electric field, and an induced osmotic pressure effect produce volume flow in the same direction as counterion flow through the membrane. Since each of these effects is proportional to the membrane charge and the imposed electric field, we classify both as electroosmotic flow. This research develops a detailed theoretical model which allows the effect of volume flow on flux enhancement to be evaluated. A detailed theoretical result for the electroosmotic flow coefficient also results from the analysis. The model assumes that transport occurs in three types of aqueous pores: positively charged, neutral, and negatively charged. For hairless mouse skin (HMS), pore size, charge, and number are evaluated from transference number, volume flow, and electrical resistance data. The flux enhancement ratio is J1/J1D = sigma Ai alpha i/[1-exp(-alpha i)], where i = pore type, and the summation runs over the three pore types. Ai is the area fraction of pore type i effective for transport; J1 and J1D are flux of species 1 with and without the electric field, respectively; and alpha i is given by alpha i = F(-delta phi/RT)[zeta 1 + (-zeta mi)Bari2Cmi(Gi + F)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2308893 TI - DC electrical properties of frozen, excised human skin. AB - DC current-voltage relationships and sodium ion transport measurements for human allograft skin immersed in saline buffers have been determined using a four terminal potentiometric method and diffusion cells of our own design. About three fourths of the skin samples were deemed suitable for study on the basis of their high resistivities and similar j-V characteristics. Most of these samples yielded sodium ion permeability coefficients less than or equal to those reported for human skin in vivo. The current-voltage relationship in these tissues was time dependent, highly nonlinear, and slightly asymmetric with respect to the sign of the applied potential. Skin resistance decreased as current or voltage increased. For current densities less than 15 microA/cm2 and exposure times of 10-20 min, this decrease was almost completely reversible; at higher current densities, both reversible and irreversible effects were observed. The overall dependence of current on voltage was nearly exponential and was satisfactorily described by an equation of the form j approximately sinh V. Diffusion potentials, sodium ion membrane transference numbers, and sodium ion flux enhancement factors during iontophoresis were measured for skin immersed both in normal saline solutions and in saline solutions of differing concentrations. The sign of the diffusion potentials and the value of the sodium ion transference number (0.51 in normal saline at pH 7.4) indicated a weak permselectivity of the skin for transport of sodium ion versus chloride. At a current density of 71 microA/cm2 and transmembrane potentials in the range of 1.1-1.6 V, the flux enhancement for sodium ion was three to five times greater than that predicted for an uncharged homogeneous membrane according to electrodiffusion theory. For transmembrane potentials less than 0.17 V, agreement of this theory with the data was better but still incomplete. PMID- 2308892 TI - Bile salt-fatty acid mixed micelles as nasal absorption promoters of peptides. I. Effects of ionic strength, adjuvant composition, and lipid structure on the nasal absorption of [D-Arg2]kyotorphin. AB - Bile salts and synthetic surfactants have been used to promote nasal absorption of peptide drugs. Although a marked increase in nasal absorption has been achieved, this may not be adequate and the possibility of adjuvant-induced membrane toxicity exists. The present study employs a rat in situ nasal perfusion technique and mixed micelles between sodium glycocholate (NaGC) and various lipids as potential nasal absorption enhancers of a stable model dipeptide, [D Arg2]kyotorphin. NaGC alone enhanced the nasal absorption of the dipeptide in a concentration-dependent manner. When linoleic acid was added to form mixed micelles with NaGC, the absorption was further enhanced (P less than 0.01). The effect of mixed micelles was synergistic and much greater than with single adjuvants. Increasing ionic strength was found to increase the adjuvant activity of both NaGC and NaGC-lipid mixed micelles. Structure of the lipid component of the mixed micelles also affected the adjuvant potency. Oleic acid, a cis unsaturated fatty acid, was more effective than elaidic acid, the trans-isomer, whereas cis-linoleic acid and trans-linolelaidic acid were equally effective (alpha = 0.05). Mixed micelles of mono-glycerides such as monoolein and monolinolein were also more effective than NaGC alone (alpha = 0.05). Micellar solubilization of these polar lipids by NaGC appears to be important for nasal absorption enhancement to occur. Reversal of the membrane permeability was also observed within approximately 20-40 min after removal of the adjuvants from the rat nasal cavity. These observations are similar to the effects of mixed micelles on the rectal mucosa and may involve the same mechanism. PMID- 2308894 TI - Solid-state chemistry and crystal structure of cefaclor dihydrate. AB - Cefaclor [7-(D-2-amino-2-phenylacetamido)-3-chloro-3-cepham-4-carboxy lic acid] crystallizes as the dihydrate. Crystals belong to space group P21, with a = 10.626(3), b = 7.1288(9), c = 14.124(3), and beta = 121.6(2). The structure was solved using direct methods and refined to an R of 0.0535. The bond lengths, angles, and conformation determined are as expected for cephalosporins. The two water molecules are held in the crystal differently. The 13C solid-state NMR spectrum of cefaclor dihydrate is also reported and is consistent with its crystal structure. PMID- 2308895 TI - Method validation revisited: a chemometric approach. AB - A validation procedure is presented that satisfies the FDA requirements of accuracy (including precision repeatability), sensitivity, linearity, dynamic range, and homoscedasticity, all with a single set of data. The procedure utilizes the corrigible error correction (CEC) technique comprised of three response curves--standard, Youden one-sample, and method of standard additions (MOSA) plots, from a total of 15 to 18 X,Y data pairs. For the bias component of accuracy, the systematic bias error of the method is quantitatively separated into its constant and proportional error components. The overall constant systematic error is further separated into the system (blank) and analyte-matrix (sample) components. The CEC data also provide an internal, i.e., in situ corrected assay for the sample for comparison with alternative method data. Statistical diagnostic tests are used for the final evaluation of the method acceptability, specifically in deciding whether or not the systematic error indicated requires a root source search for its removal or is simply a calibration constant of the method. PMID- 2308896 TI - Bioavailability improvement of mycophenolic acid through amino ester derivatization. AB - The potential bioavailability improvement of mycophenolic acid (MPA), 1, through ester derivatization was evaluated in monkeys at a dose of 20 mg/kg in this study. The acetyl solketal ester 3 was found to have excellent partition properties but poor aqueous solubility. Thus, even though it can be converted rapidly to MPA by plasma and liver enzymes, it showed poor oral bioavailability (56% of MPA) in monkeys. The bioavailability of the morpholinoethyl ester 4 and the acetyl morpholinoethyl ester 5, on the other hand, was found to be 236 and 150% that of MPA, respectively. Since ester 5 has greater aqueous solubility, but similar chemical stability and enzymatic hydrolysis rates compared to ester 4, the better bioavailability of ester 4 may result from its greater partitioning into the gastrointestinal membranes. PMID- 2308898 TI - Quantitation of the relative amounts of anhydrous carbamazepine (C15H12N2O) and carbamazepine dihydrate (C15H12N2O.2H2O) in a mixture by solid-state nuclear magnetic resonance (NMR). AB - The application of solid state nuclear magnetic resonance (NMR) for the quantitation of the relative amounts of carbamazepine anhydrate (I) and carbamazepine dihydrate (II) in a mixture is presented. The techniques of cross polarization, dipolar decoupling, and magic angle spinning have been used to obtain high-resolution NMR spectra of the samples in the solid state. Although the chemical shifts of I and II were similar, the proton spin lattice relaxation time of II was much shorter than that of I. A delay time of 10 sec between pulses resulted in saturation of the signal from I and in a spectrum arising solely from II. The dependence of the observed signal intensity on the contact time was evaluated for II and glycine, the internal standard, to allow theoretical estimation of the peak area ratios. Various molar ratios of I and II were then mixed with glycine, and the resulting peak area ratios of II to the area of the alpha and the carbonyl carbons of glycine was linearly related to the relative proportion of II in the mixture. PMID- 2308897 TI - Mechanism of ethanol-enhanced estradiol permeation across human skin in vivo. AB - The influence of ethanol on the permeation of 17 beta-estradiol (estradiol) across viable human skin in vivo was investigated with the human skin sandwich flap model. Maintaining continuous delivery of a constant concentration of the solute in phosphate-buffered saline, pH 7.4 (PBS), or mixtures of ethanol in PBS to the skin surface revealed that steady-state flux of estradiol was achieved within 30-60 min and maintained throughout 4 hr. The 10-fold decrease in in vivo flux and permeability coefficient (Kp) of tracer estradiol solutions in ethanol or ethanol solutions compared with PBS vehicle reflected the 10-fold difference in the apparent partition coefficients (Km) of estradiol from the respective vehicles into isolated human stratum corneum. Neither the stratum corneum thickness nor the diffusion coefficient of estradiol was significantly different among the vehicles tested. In vivo flux of estradiol in ethanol or ethanol solutions across viable human skin was increased with saturated solutions of estradiol. Further, in vivo flux of estradiol from vehicles such as PBS, ethanol, and ethanol mixtures, which minimally alter the rate-limiting barrier, can be successfully predicted with knowledge of only two physicochemical parameters, the estradiol concentration in the vehicle and the Km of estradiol from the vehicle into isolated human stratum corneum. PMID- 2308899 TI - Disposition of bismuth in the rat. I. Red blood cell and plasma protein binding. AB - The plasma protein and red blood cell binding profile of bismuth was investigated as a function of bismuth concentration. The binding of bismuth to human serum albumin, bovine serum albumin, and human plasma was also evaluated by ultrafiltration and the data analyzed by nonlinear regression techniques. The binding of bismuth to plasma proteins was nonlinear and decreased as a function of incubation concentration and appeared to be limited by the number of ionized l cysteine residues available for binding. In the concentration range studied, bismuth was associated primarily with the red blood cell fraction of whole blood obtained from male Sprague Dawley rats. The data indicated that binding to proteins was of moderate affinity, and in whole blood it was present primarily in the red blood cell compartment. PMID- 2308900 TI - Microbial metabolism studies of the antimalarial drug arteether. AB - Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized by a number of microorganisms. Large-scale fermentation with Aspergillus niger (ATCC 10549) and Nocardia corallina (ATCC 19070) have resulted in the isolation of four microbial metabolites which have been characterized using two-dimensional nuclear magnetic resonance (2D-NMR) techniques. These metabolites have been identified as "AEM1" (2), 3 alpha hydroxydeoxyarteether (3), 3 alpha-hydroxydeoxydihydroartemisinin (4), and deoxydihydroartemisinin (5). PMID- 2308901 TI - Disposition of antipyrine and acetaminophen given alone and in combination to human subjects. PMID- 2308902 TI - Class III antiarrhythmic action linked with positive inotropy: acute electrophysiological and inotropic effects of amiodarone in vitro. AB - Negative inotropy is an adverse feature of most antiarrhythmic drugs. Positive inotropy, however, has been demonstrated for some drugs with class III antiarrhythmic action. Although amiodarone exerts its antiarrhythmic effect by an interplay of different actions on cardiac cells, it has been regarded to be the prototype class III drug due to its prolongation of action potential duration. The present study was designed to test the hypothesis that class III antiarrhythmic action and positive inotropy may be linked. We compared the effects of amiodarone in Cordarone and its solvent Tween 80 on automaticity, refractoriness and inotropy. Two series of experiments were done; one with spontaneously beating rat atria to study the effects on sinus node function, and one with electrically stimulated left atria to study the effects on excitability, refractoriness and inotropy. Amiodarone 1 x 10(-4) M decreased spontaneous heart rate by 13% and prolonged sinus node recovery time by 105%. Without affecting the excitability amiodarone prolonged the effective refractory period by 12%. At the same time contractile force increased by 12%. Lower concentration of amiodarone (5 x 10(-6) M) or Tween 80 had no significant effects. In conclusion, amiodarone exerts acute electrophysiological and inotropic effects in vitro. The class III antiarrhythmic action of amiodarone is linked with positive inotropy. PMID- 2308903 TI - The in vitro and in vivo effects of lead on delta-aminolevulinic acid dehydratase and pyrimidine 5'-nucleotidase. AB - The in vitro and in vivo effects of lead on the activity of pyrimidine-5' nucleotidase (P5N, E. C. 3.1.3.5) and delta-aminolevulinic acid dehydratase (ALA D, E.C. 4.2.1.24) were studied. Incubation of blood with lead at concentrations of up to 3 mumol/l (about 60 micrograms/dl) did not appear to affect the activity of P5N, while the activity of ALA-D decreased dose-dependently with lead. Administration of lead caused a marked and rapid suppression of ALA-D in rats. The suppression of lead on P5N appeared to be a rather slow process. The decrease of its activity only came into effect 20 days after administration with lead. these findings suggest that lead induced P5N inhibition is a slow process while the suppression of ALA-D activity occurs much earlier. PMID- 2308904 TI - Aminotriazole effects on lung and heart H2O2 detoxifying enzymes and TBA-RS at two pO2. AB - In order to clarify the physiological role in vivo of H2O2-detoxifying enzymes at low and high levels of O2 tension we studied catalase (CAT), glutathione peroxidases (GP), and in vivo peroxidation (TBA-RS) in the lung and heart of Rana perezi frogs chronically treated with hyperoxia, aminotriazole (AT) -a CAT inhibitor-, or both. Hyperoxia did not change CAT, GP or TBA-RS. Aminotriazole caused an almost complete depletion of CAT, a 30% decrease of GP and a 132% (lung) to 200% (heart) increase of TBA-RS. Changes similar to these were found in the group treated with AT in hyperoxia. No mortality or changes in total or organ weight occurred in the experimental groups. Main conclusions are: (1) The maximal hyperoxia tolerance showed by frogs among vertebrates does not need antioxidant enzyme induction from lung or heart and is probably related to the presence of high constitutive levels of GP in relation to metabolic rate. (2) Even in normoxia the tissues present significant amounts of H2O2, and CAT is needed to avoid oxidative damage. GP does not compensate its absence. The implications of these results in relation to oxygen toxicity in man is discussed. PMID- 2308906 TI - Tissue distribution and elimination of perfluorodecanoic acid in the rat after single intraperitoneal administration. AB - Tissue distribution, metabolism, and excretion of perfluorodecanoic acid (PFDA) after a single intraperitoneal dose (20 mg/kg) were studied in female and male Wistar rats. PFDA accumulated in the serum and tissues of the rats. In the serum, more than 99% of PFDA was bound by the serum proteins. In the liver, anionic and esterified PFDA were detected. Metabolic oxidation of PFDA was not observed. PFDA was not excreted in urine either by females or males during 14 days after the administration. At the same time, about 0.5% of the administered PFDA dose was excreted daily in the faeces by both sexes. In spite of the analogical structure with perfluorooctanoic acid (PFOA), which is rapidly eliminated in urine by the female rats, PFDA accumulated similarly in females and males. The reduced elimination of PFDA partially explains its greater toxicity to rats in comparison with PFOA. PMID- 2308905 TI - The rhesus monkey as a model for studies of pregnancy induced changes in metoprolol metabolism. AB - Five pregnant Rhesus monkeys were catheterized in the hepatic and femoral veins. They were simultaneously given 168 or 176 micrograms of 3H-metoprolol intravenously, and 9 mg of metoprolol per kg body weight orally. The same procedure was repeated a few months after delivery. Analyses of the unlabelled drug in blood were made by gas-chromatography and of the 3H-labelled metoprolol, by liquid scintillation. The apparent volume of distribution as well as the terminal half-lives of metoprolol were in the same range during pregnancy and in non-pregnancy. The oral bioavailability of metoprolol was lower (6-22%) during pregnancy than in non-pregnancy (9-49%). The apparent oral clearance and the intrinsic hepatic clearance were in a similar range although there was a greater variation in the intrinsic clearance values. The former clearance estimate was lower in the non-pregnant state only for three of the five animals. The systemic clearance varied very little and was in the same range during pregnancy and in non-pregnancy. The changes in apparent oral clearance and in oral bioavailability of metoprolol between the pregnant and non-pregnant Rhesus monkey are similar to the changes observed in pregnant women, although the absolute values are different. PMID- 2308907 TI - Cyclosporin metabolism in human liver microsomes and its inhibition by other drugs. AB - The metabolism of cyclosporin was studied in human liver microsomes. There was no metabolism in the presence of cytochrome C or carbon monoxide or in the absence of cofactors, suggesting metabolism by cytochrome P-450 enzymes. The metabolism was inhibited by ketoconazole and erythromycin, by the steroids methylprednisolone and oestradiol, and by the calcium antagonists diltiazem, nifedipine, prenylamine and verapamil. These in vitro findings correlate well with previously published clinical reports suggesting that these drugs may inhibit the metabolism of cyclosporin in vivo. Our observations suggest that metabolic interactions between cyclosporin and other drugs in vivo may be predicted in vitro under proper experimental conditions. PMID- 2308908 TI - A sulfate conjugate of cyclosporin. AB - A metabolite of cyclosporin A was isolated from human bile and plasma. The material was identified as a sulfate conjugate by plasma desorption time-of flight mass spectrometry and by in vitro technique using human liver preparations and radiolabeled substrates. A sulfate ester at the beta-carbon on the amino acid no. 1, the methylbutenyl-threonine amino acid, of cyclosporin was synthesized as a reference, and found to have the same plasma desorption time-of-flight and direct chemical ionization mass spectrum as the isolated metabolite. It also had the same chromatographic properties on both an ion-pair reversed phase system and an ion-exchanger. Hydrolysis with sulfuric acid on the purified and synthetic metabolite gave free cyclosporin. The amino acids in the metabolite, analyzed by gas chromatography/mass spectrometry, were the same as those in cyclosporin. Free cyclosporin was not found upon hydrolysis with commercial sulfatases. PMID- 2308910 TI - Metabolic interaction between endogenous methanol and exogenous ethanol studied in human volunteers by analysis of breath. AB - Ethanol was administered to 5 healthy volunteers by intravenous infusion to maintain a constant blood-alcohol concentration (BAC) of about 0.8 mg/ml (17.4 mmol/l) for 3-4 hr. Before starting the infusion and at 15 min. intervals thereafter, we analysed end-expired air by a highly sensitive gas chromatographic method. The presumed concentrations of ethanol and methanol in blood were estimated indirectly from measurements in the breath. The liquid/air partition coefficients of methanol were determined for whole blood, plasma, water, and corn oil when dilute solutions were equilibrated at 34 degrees and 37 degrees. The results at 37 degrees were 2709 +/- 165, 3400 +/- 86, 2948 +/- 221 and 44.5 +/- 6.3 for whole-blood/air, water/air, plasma/air and corn-oil/air respectively. During infusion of ethanol, the concentrations of endogenous methanol in blood rose from being between 0.4-0.8 mg/l to reach between 1.2-3.4 mg/l with a substantial inter-subject variation in rate of increase. Our results confirm the existence of endogenous methanol in human blood and breath and demonstrate that the concentrations present can rise to abnormally high levels when the body is flooded with exogenous ethanol. PMID- 2308909 TI - Effect of N-acetyl-cysteine, D-penicillamine and buthionine sulfoximine on glutathione levels and CNS oxygen toxicity in rats. AB - The effect of glutathione (GSH) synthesis modulators - L-buthionine sulfoximine (BSO), N-acetyl cysteine (NAC) and D-penicillamine (DPA) - on the susceptibility of rat CNS to O2 toxicity was investigated. The animals were given 5% sucrose or 40 mM solutions of BSO, NAC or DPA in 5% sucrose as drinking water for one week and sacrificed prior to or after exposure to 4.5 ATA O2. The GSH content in brain, liver, lung and blood, and the activity of glutathione peroxidase (GSH Px), glutathione reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PD) and superoxide dismutase (SOD) in brain and lungs were measured. The brain GSH content and the enzyme activities were not changed by any of the drugs. BSO decreased the GSH content in all the other tissues; NAC and DPA treatments increased the GSH content in lungs, blood and/or liver. The CNS toxicity threshold as measured by the time of appearance of first electrical discharge (FED) on ECoG recording was not changed by NAC or DPA, but BSO brought about a significant delay in FED time. It is suggested that increased extracerebral GSH levels do not protect against CNS oxygen toxicity, and that BSO provides some protection, probably via a glutathione-independent mechanism. PMID- 2308911 TI - The mauve factor of porphyria, 3-ethyl-5-hydroxy-4,5-dimethyl-delta-3-pyrroline-2 one: effects on behaviour of rats and mice. AB - The monopyrrole, 3-ethyl-5-hydroxy-4,5-dimethyl-delta 3-pyrroline-2-one (HPL), was given by intraperitoneal injection to rats (0.65 mmol/kg) and to mice (0.98 and 1.95 mmol/kg). Behaviour of the rats was assessed for 1.5 hr after injection by monitoring their spontaneous activity, while behaviour of the mice was examined by ethological procedures during dyadic encounters over a 5 min. period at 50-60 min. following injection. Activity of the rats, once habituated to the cage, was reduced by HPL. No other abnormalities were discernible. In mice, HPL at 1.95 mmol/kg increased the frequency of "head twitch" and evoked a smaller increase of "backward locomotion". There were no changes in overall agonistic, social or non-social behaviour in the HPL treated mice. Plasma concentrations of HPL in mice treated with the highest dose level amounted to 0.3 +/- 0.1 mmol/l, many-fold above its plasma concentrations during acute porphyric attacks in man. It thus appears that in rodents HPL has slight behavioural activity, but that it is unlikely to play any significant role in the psychiatric disturbances of acute porphyria. PMID- 2308912 TI - Antinociceptive effects and spinal distribution of two adenosine receptor agonists after intrathecal administration. PMID- 2308913 TI - [Results of the epidemiology of lung cancer in females]. AB - In the context with an extensive pilot study investigating risk factors for lung cancer, aetiological and clinical questions were analysed for lung cancer mortality in women. In a first step all available data sources about the prevalence of smoking in the FRG were used to determine the correlation between the prevalence of smoking and lung cancer mortality. 88% of the variance (R2) of lung cancer mortality for women could be explained by smoking. In a second step medical records of 133 female lung cancer patients from three hospitals were analysed with regard to the histological types of lung cancer and smoking. Small cell lung cancers were more frequent among female smokers while adenocarcinoma was more prevalent among non-smokers. Survival analysis for 421 men and 97 women showed a significantly longer survival time for women as compared to men, taking into account other relevant prognostic factors. The association between smoking and lung cancer is discussed and analysed in greater detail. PMID- 2308915 TI - United States and Canadian Academy of Pathology. Annual meeting. Boston, March 4 9, 1990. Abstracts. PMID- 2308916 TI - The undifferentiated malignant tumor, a continuing challenge. PMID- 2308914 TI - [Bronchiolitis obliterans following nitrogen dioxide (NO2) inhalation: clinical roentgenologic-histologic study]. AB - A case of bronchiolitis obliterans after prior inhalation of NO2 is described. The diagnosis was confirmed histologically following diagnostic thoracotomy and biopsy by means of pulmonary wedge resection. The clinical course of the case was compatible with the typical phases described in the literature, and the condition underwent complete remission following treatment with corticoids. PMID- 2308917 TI - Disseminated Pneumocystis carinii infection causing extrapulmonary organ failure: clinical, pathologic, and immunohistochemical analysis. AB - Pneumocystis carinii pneumonia is an important infection in the immunocompromised host, and the rate of symptomatic infections has risen dramatically with the advent of immunosuppressive therapies and infections with the human immunodeficiency virus (HIV). However, dissemination of P. carinii is thought to be an unusual event, and it is rarely suspected of causing extrapulmonary symptomatology. We have recently examined the cases of patients with acquired immunodeficiency syndrome (AIDS) who demonstrated at autopsy extrapulmonary infection with P. carinii. Three of these patients had widespread pneumocystosis, and in one patient dysfunction in several organs could be directly attributed to effects of P. carinii, which contributed to his death. The possible factors leading to dissemination of P. carinii are discussed. We also describe the use of a newly developed monoclonal antibody to P. carinii in detecting extrapulmonary infections. PMID- 2308918 TI - Mucosal defense and concept of cytoprotection. PMID- 2308919 TI - Assessment of proliferative rate of breast cancer by Ki-67 monoclonal antibody. AB - The proliferative activity of 163 primary breast cancers was assessed by immunocytochemistry with the mouse monoclonal antibody Ki-67, which recognizes a nuclear antigen expressed in all phases of the cell cycle except for Go. The overall frequency distribution of Ki-67 staining was of exponential type, with percentage of positive staining cells ranging from 0.3 to 88.3%, with a median value of 10.1%. No relationship was observed between Ki-67 values and menopausal status of patients. A significant positive correlation was found between Ki-67 values and tumor grade, especially mitotic grade. Estrogen Receptors (ER) were assayed by immunocytochemistry with ER-ICA method and by dextran-coated charcoal method (DCC) in 129 and 141 tumors, respectively. A negative correlation was found between the ER content by both methods and Ki-67 score. Eighty-nine percent of cases with Ki-67 value less than 10.1% contained more than 10% ER-ICA-positive cells. Progesterone receptors (PgR) were assayed by immunocytochemistry with PgR ICA method and by DCC in 62 and 141 tumors, respectively. A negative correlation was observed between the PgR content by both methods and Ki-67 score. No correlation was found between Ki-67 score and lymph node involvement by tumor. These findings suggests that Ki-67 score could be used as an independent prognostic marker, useful to distinguish different risk for recurrence within the two clinically heterogeneous groups of N- and N+ patients. PMID- 2308920 TI - The spectrum of pancreatic pathology in patients with AIDS. AB - Clinical studies have indicated that pancreatitis is a common cause of morbidity in patients with acquired immunodeficiency syndrome (AIDS). In order to assess the morphologic basis of this pancreatic disease, we reviewed 82 autopsies performed on AIDS patients at The Johns Hopkins Hospital. Pancreatic lesions were detected in 52 (65%) of these, and could be classified into three broad categories: acinar dilatation by inspissated secretions (24 cases), acute pancreatitis (recent or remote, 18 cases), and opportunistic infections or cancers affecting the pancreas (23 cases). To better assess the importance of these lesions, particularly the acinar dilatation, 82 age-race-sex-matched controls were evaluated in a blinded comparison. The frequency of acinar dilatation and acute pancreatitis was similar in cases and controls. Only one control was found to have an opportunistic infection, and no opportunistic cancer was detected in controls. There were no unexplained lesions found in the AIDS cases which might be attributed to direct human immunodeficiency virus (HIV) infection. These data confirm clinical reports that the pancreas is frequently affected in AIDS patients. We propose that the clinical evidence of pancreatitis reported in these patients may be due to the frequent opportunistic lesions demonstrated by this series. PMID- 2308921 TI - Allergy-related proctocolitis in infants: diagnostic usefulness of rectal biopsy. AB - To evaluate the diagnostic utility of rectal mucosal biopsies in infants with proctocolitis, we compared the clinical and histologic features of an allergy related group (N = 36) with those of normal (N = 12) and inflammatory (N = 8) controls. Clinical features were nondiscriminatory among the three groups of patients, except for an increased absolute peripheral eosinophil count in the allergic group. Similarly, morphologic evidence of proctitis (cryptitis and crypt abscesses) and small or moderate numbers of eosinophils (less than or equal to 60 per ten high power fields) in the lamina propria of the biopsies did not discriminate among the three groups. However, large numbers of eosinophils (greater than 60 per ten high power fields) and eosinophils located in the muscularis mucosae or as the predominant cell in crypt abscesses were significantly associated with allergy-related disease. No histologic features of chronic colitis were noted in the allergy-related group. Thus, in tandem with the remainder of the clinical data, rectal mucosal biopsy is a useful adjunct in the diagnosis of allergic proctocolitis. PMID- 2308922 TI - Histology of early lesions of AIDS-associated Kaposi's sarcoma. AB - The original cutaneous biopsy specimens of 93 patients who presented themselves to the Memorial Sloan-Kettering Cancer Center with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) were systematically reviewed for 23 histologic variables. KS was the initial manifestation of AIDS in all of the patients. The vast majority of patients presented with plaque histology of KS. Early lesions of KS were characterized by the presence of dilated vascular spaces haphazardly arranged in the biopsy specimen, a sparse inflammatory cell infiltrate composed of lymphocytes (usually without plasma cells), and aggregates of cuboidal cells with the appearance of epithelioid cells. Individually necrotic tumor cells were present in nearly every case. Spindle cells arranged in fascicles or nodules were seen in a minority of cases. These data provide an overview of the different histologic patterns seen in initial lesions of AIDS associated KS and may lead to better understanding of the pathogenesis of this tumor. PMID- 2308923 TI - Detection of occult CNS involvement of follicular small cleaved lymphoma by the polymerase chain reaction. AB - A patient with follicular small cleaved lymphoma presented with an unusual clinical relapse in the central nervous system (CNS) without morphologic evidence of lymphoma cells in the cerebral spinal fluid (CSF). Molecular genetic analysis of the small number of cells in the CSF after in vitro DNA amplification by the polymerase chain reaction demonstrated the presence of an abnormal translocation sequence between chromosomes 14 and 18. A similar translocation could be detected from the original fixed archival lymph node biopsy and from a small proportion of circulating mononuclear cells. These results indicated that occult lymphoma cells were present in the CSF and peripheral blood. Secondary CNS lymphoma involvement was identified at autopsy. This case demonstrates the enhanced sensitivity of lymphoma diagnosis from poorly cellular specimens after in vitro DNA amplification. PMID- 2308924 TI - Polymorphous low grade adenocarcinoma of minor salivary gland: a clinicopathologic and comparative immunohistochemical study. AB - Retrospective review of seven cases of polymorphous low grade adenocarcinoma (PLGA) revealed that the original histologic diagnosis in five instances was mixed tumor (four benign and one malignant). Comparison of PLGA tumors with eleven representative cases of benign pleomorphic adenoma of minor salivary gland (BPA) showed marked similarity in cytologic features. PLGA and BPA also exhibited similar mucohyaline and/or fibromyxoid stromal components. In contrast, tumor margins of the two neoplasms were quite different; margins of PLGA were consistently infiltrative, whereas those of BPA were generally well circumscribed and encapsulated. Immunophenotypic comparison confirmed the glial fibrillary acidic protein (GFAP) positivity in BPA reported by others, whereas cases of PLGA were uniformly nonreactive with this antibody. Although previous reports have emphasized the histologic similarities of PLGA and adenoid cystic carcinoma, our findings indicate that differentiation of PLGA from BPA may represent a more common diagnostic problem. Awareness of comparative histologic features is important in the differential diagnosis of these minor salivary gland neoplasms. Also, monoclonal GFAP may be useful in distinguishing cases of PLGA from BPA where histologic features are otherwise similar. PMID- 2308925 TI - Re: A. R. Rhodes, M. C. Mihm, and M. A. Weinstock. Dysplastic Melanocytic Nevi: a Reproducible Histologic Definition Emphasizing Cellular Morphology. Mod Pathol 2:306, 1989. PMID- 2308926 TI - Host regulation of the cauliflower mosaic virus multiplication cycle. AB - The DNA genome of cauliflower mosaic virus (CaMV) replicates in the cytoplasm of infected plant cells by reverse transcription of an RNA template. Viral RNA is generated in the nucleus by transcription of an episomal minichromosome containing supercoiled DNA. We have assessed the relative activities of the nuclear and cytoplasmic phases of the CaMV multiplication cycle by monitoring unencapsidated viral DNA forms and polyadenylylated RNAs in different organs of one host plant and in different host species. Systemically infected leaves of a highly susceptible host, turnip (Brassica rapa), contained abundant 35S RNA and 19S RNA transcripts and unencapsidated reverse transcription products but relatively little supercoiled DNA. In contrast, supercoiled DNA accumulated in roots and other tissues of turnip plants but without significant amounts of steady-state viral RNA. Infected but asymptomatic leaves of a less susceptible CaMV host, kohlrabi (Brassica oleracea), contained supercoiled DNA almost exclusively but negligible viral RNA and DNA products of reverse transcription. An allotetraploid species, rape (Brassica napus), exhibited infection characteristics and minichromosome expression levels intermediate between the other two species from which it was derived. We conclude that expression of the CaMV minichromosome is a key phase of the virus multiplication cycle, which is regulated differentially in organs of a highly susceptible host species. Furthermore, this regulation exhibits genetic variation among different Brassica species and controls host susceptibility to CaMV infection. PMID- 2308927 TI - Reversible and irreversible labeling and autoradiographic localization of the cerebral histamine H2 receptor using [125I]iodinated probes. AB - Iodoaminopotentidine (I-APT)--i.e., N-[2-(4-amino-3-iodobenzamido)ethyl]-N'-cyano N''-(3-[3- (1-piperidinylmethyl)phenoxy]propyl)guanidine--represents one of the most potent H2-receptor antagonists known so far. In membranes of guinea pig brain 125I-APT bound reversibly, selectively, and with high affinity (Kd = 0.3 nM) to a homogeneous population of sites unambiguously identified as H2 receptors by inhibition studies conducted with a large panel of antagonists. 125I-APT binding was also inhibited by histamine, and the effect was modulated by a guanyl nucleotide, which is consistent with the association of the H2 receptor with a guanine nucleotide binding regulatory protein. The low nonspecific binding of 125I-APT generated high contrast autoradiographic pictures in brain sections and established the precise distribution of H2 receptors. Their highly heterogeneous distribution and laminated pattern in some areas--e.g., cerebral and hippocampal cortices--suggest their major association with neuronal elements. These localizations were more consistent than those of H1 receptors with the distribution of histaminergic projections, indicating that H2 receptors mediate a larger number of postsynaptic actions of histamine--e.g., in striatum. Colocalizations of H1 and H2 receptors in some areas account for their known synergistic interactions in cAMP formation induced by histamine. The distribution of 125I-APT binding sites did not strictly parallel that of the H2-receptor linked adenylate cyclase activity, which may reflect heterogeneity among H2 receptors. After UV irradiation and SDS/PAGE analysis, [125I]iodoazidopotentidine (125I-AZPT), a photoaffinity probe derived from 125I-APT, was covalently incorporated in several peptides, among which the labeling of two peptides of 59 and 32 kDa was prevented by H2 antagonists, suggesting that they correspond to H2 receptor binding peptides or proteolysis products of the latter. These probes should be useful for sensitive radioassays, localization, purification, and molecular studies of the H2 receptor, which were previously impracticable. PMID- 2308928 TI - 1H NMR visibility of mammalian glycogen in solution. AB - High-resolution 1H NMR spectra of rabbit liver glycogen in 2H2O were obtained at 500 MHz, and several resonances were assigned by comparison with the chemical shifts of alpha-linked diglucose molecules. The NMR relaxation times T1 and T2 of glycogen in 2H2O were determined to be 1.1 and 0.029 s, respectively. The measured natural linewidth of the carbon-1 proton (12 +/- 2 Hz) is in excellent agreement with that calculated from T2. The visibility measurements made by digesting glycogen and comparing glucose and glycogen signal intensities demonstrate that in spite of the very high molecular weight, all of the proton nuclei in glycogen contribute to the NMR spectrum. The result is not unexpected, since 100% NMR visibility was previously observed from the carbon nuclei of glycogen, due to the rapid intramolecular motions. PMID- 2308929 TI - Comparison of human ZFY and ZFX transcripts. AB - ZFY is a candidate for the primary sex-determining gene (TDF, testis-determining factor) on the human Y chromosome. We have isolated cDNA clones of ZFY and its homologue on the X chromosome, ZFX. The transcripts of these genes are very similar to each other and encode predicted proteins of equal size. The conceptual amino acid sequence of both proteins contains an acidic domain, similar to the activation domain of transcription factors, and a potential nucleic acid-binding domain of 13 "zinc fingers." We have used the polymerase chain reaction to demonstrate the expression of ZFY and ZFX in a wide range of adult and fetal human tissues and to show that ZFX is expressed from the inactive X chromosome present in human-mouse hybrids. PMID- 2308930 TI - Vitamin D-mediated modifications in protein-DNA interactions at two promoter elements of the osteocalcin gene. AB - By the combined use of DNase I footprinting, electrophoretic mobility-shift assay, and methylation interference analysis, we have identified a series of sequence-specific protein-DNA interactions in the 5' flanking region of the rat osteocalcin gene. Stimulation of osteocalcin gene expression by 1,25 dihydroxyvitamin D3, a physiologic mediator of this bone-specific gene in vitro and in vivo, is associated with modifications in the binding of ROS 17/2.8 cell nuclear factors to two promoter segments that up-regulate transcription. One segment located between -462 and -437 exhibits a vitamin D-dependent increase in sequence-specific binding of nuclear factors. This element (CTGGGTGAATGAGGACATTACTGACC), identified at single nucleotide resolution, contains a region of hyphenated dyad symmetry and shares sequence homology with consensus steroid-responsive elements and with the sequence that has been identified as the vitamin D receptor binding site in the human osteocalcin gene. We have also observed that vitamin D stimulation of osteocalcin gene expression results in a 5-fold increase in protein binding to the region of the osteocalcin box, a 24-nucleotide segment in the proximal promoter with a CCAAT motif as the central core. Our results demonstrate protein-DNA interactions in a vitamin D responsive element and in a second sequence, the osteocalcin box, both of which are involved in the physiologic regulation of the osteocalcin gene in response to 1,25-dihydroxyvitamin D3. PMID- 2308932 TI - Phospholipids enhance the binding of peptides to class II major histocompatibility molecules. AB - The binding of a lysozyme and ovalbumin peptide to purified class II major histocompatibility molecules in detergents was increased by the addition of certain lipids. Natural lipids from B lymphoma cells enhanced the binding and so did phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and cardiolipin. Phosphatidylethanolamine, sphingomyelin, and cholesterol had no effect. There was no major difference between the effects of a phospholipid and its lyso derivative. As studied with phosphatidylcholine, the increase in peptide binding was also dependent on the fatty acid composition of the lipid. The binding affinity was increased 10- to 50-fold in the presence of lipid as a result of an increase in the association rate while the off-rate remained essentially unchanged. Our results suggest that lipids, directly or indirectly, induce conformational changes in class II molecules that favor their peptide binding property. PMID- 2308933 TI - Application of scanning electrochemical microscopy to biological samples. AB - The scanning electrochemical microscope can be used in the feedback mode in two dimensional scans over biological substrates to obtain topographic information at the micrometer level. In this mode, the effect of distance between a substrate (either conductive or insulating) and a scanning ultramicroelectrode tip on the electrolytic current flowing at the tip is recorded as a function of the tip x-y position. Scans of the upper surface of a grass leaf and the lower surface of a Ligustrum sinensis leaf (which show open stomata structures) immersed in aqueous solution are shown. Scans of the upper surface of an elodea leaf in the dark and under irradiation, where the tip reaction is the reduction of oxygen produced by photosynthesis, demonstrate the possibility of obtaining information about the distribution of reaction sites on the substrate surface. PMID- 2308931 TI - Glutathione is required for intestinal function. AB - Glutathione (GSH) deficiency produced in mice by giving buthionine sulfoximine leads to severe degeneration of the epithelial cells of the jejunum and colon. This is prevented by giving GSH monoester (orally or i.p.) and also by giving GSH (orally, but not i.p.). The i.p. administration leads to high plasma levels of GSH but does not appreciably increase GSH levels in intestinal mucosa or pancreas. These and previous studies on lens, lung, lymphocytes, liver, heart, and skeletal muscle indicate that there is very little, if any, transport of intact GSH from plasma to these tissues. Cells can use extracellular GSH by a pathway involving its cleavage, uptake of products and intracellular GSH synthesis. Epithelial cells of the gastrointestinal tract may use this pathway and can also take up lumenal GSH (which arises partly from the bile) by a mechanism(s) that may involve transport of dipeptides or of GSH. It is suggested that biliary GSH normally functions in the protection of intestinal mucosa. Administration of GSH may be protective of the gastrointestinal epithelium and may also serve as a good source of cysteine moieties for intracellular GSH synthesis in the gastrointestinal tract and in other tissues. Administration of GSH delivery agents such as GSH esters is more effective than administration of GSH in increasing cellular and mitochondrial levels of GSH. PMID- 2308935 TI - Chromosome ends in Drosophila without telomeric DNA sequences. AB - We have recovered terminal chromosome deletions of the X chromosome of Drosophila [Df(1)RT; RT = receding tips] that break in various positions of the yellow gene (y) region and delete all distal DNA sequences. Terminal DNA fragments are heterogeneous in length. Molecular cloning and sequencing of the terminal DNA fragments revealed that the broken ends of the deleted chromosomes do not carry any telomeric DNA sequences, yet the broken chromatids do not fuse to one another. Moreover, we confirmed by sequence analysis of 49 independently cloned terminal DNA fragments from two RT lines collected at different times that they lose DNA sequences from their distal ends at a rate of 70-75 base pairs per fly generation. We calculate that the rate of loss from these ends is consistent with the removal of an octanucleotide RNA primer at each round of DNA replication in the germ line. PMID- 2308934 TI - Regulation of mRNA abundance in activated T lymphocytes: identification of mRNA species affected by the inhibition of protein synthesis. AB - Inhibition of protein synthesis has often been observed to increase the concentration of mRNAs that encode proteins associated with the regulation of cell division. As two-dimensional gel electrophoresis permits the simultaneous monitoring of individual elements in large populations of gene products, we have used this technique to assess the effect of cycloheximide treatment on the mRNA complement of activated mouse T cells in an objective fashion. Two-dimensional gels of proteins generated by cell-free translation of mRNA from T-cell blasts display about 400 spots; only 5 of these are reproducibly enhanced by cycloheximide treatment and about 4 are diminished. The cDNA cloning vector lambda jac allows analysis of large arrays of molecular clones by cell-free expression, and we have used it in a sibling selection scheme to isolate a clone of one of the prominently induced mRNA species, which we refer to as chx1. chx1 mRNA concentration is increased by cycloheximide treatment of activated B cells, as well as T cells, and it is rapidly and transiently induced, in a cycloheximide enhanced manner, upon serum stimulation of resting 3T3 fibroblastoid cells. The chx1 protein is hydrophilic, is slightly basic, and has patches of homology with the Jun-D gene product. The chx1 gene is remarkable in its lack of detectable introns and of strong bias against CpG dinucleotides. PMID- 2308936 TI - Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane bound alloantigen. AB - The properties of transmembrane and soluble transplantation antigens were compared with respect to the induction of tolerance and the selection of the T cell repertoire. For this purpose, transgenic (H-2b x H-2d)F1 mice were constructed that carry integrated copies of a modified H-2Kk gene resulting in the secretion from various cell types including thymocytes of soluble H-2Kk molecules. Despite the presence of H-2Kk antigen, these mice were still able to generate an H-2Kk-specific T-cell response. This response was comparable to that produced by normal littermates when stimulated with cells expressing membrane H 2Kk in a mixed lymphocyte reaction. In contrast, only transgenic mice failed to generate a cytolytic T-cell response to soluble H-2Kk antigen expressed by recombinant vaccinia virus and presented by the H-2Db molecule. These data imply the presence of two populations of alloreactive cytolytic T cells. A small fraction of T cells recognizes alloantigen as antigenic peptide(s) presented by other major histocompatibility complex class I molecules and tolerance can be induced in this population by soluble alloantigen. The majority of T cells, however, require the whole cell membrane-expressed class I molecule for recognition. This population is not affected by tolerance induction to the soluble major histocompatibility complex class I molecule. PMID- 2308937 TI - Isolation and characterization of cDNA encoding the 80-kDa subunit protein of the human autoantigen Ku (p70/p80) recognized by autoantibodies from patients with scleroderma-polymyositis overlap syndrome. AB - Anti-Ku (p70/p80) autoantibodies in patients with scleroderma-polymyositis overlap syndrome recognize a 70-kDa/80-kDa protein heterodimer which binds to terminal regions of double-stranded DNA. In the present study, we isolated full length cDNAs that encode the 80-kDa Ku subunit. Initial screening of a human spleen cDNA library with anti-Ku antibodies yielded a cDNA of 1.0 kilobase (kb) (termed K71) encoding a portion of the 80-kDa Ku polypeptide (identification based on immunological criteria). In RNA blots, this cDNA hybridized with two mRNAs of 3.4 and 2.6 kb. In rescreening of a cDNA library constructed from simian virus 40-transformed human fibroblast mRNA with the K71 cDNA as a hybridization probe, three positive clones were isolated, and that bearing the longest insert (termed Ku80-6) was selected for further characterization. In vitro transcription and translation experiments produced an immunoprecipitable polypeptide which comigrated with the 80-kDa Ku subunit. The Ku80-6 cDNA proved to be 3304 nucleotides in length, with an additional poly(A) tail, closely approximating the size of the larger mRNA. It contains a single long open reading frame encoding 732 amino acids (Mr = 82,713). The putative polypeptide has a high content of acidic amino acids and a region with periodic repeat of leucine in every seventh position which may form the "leucine zipper" structure. In genomic DNA blots, probes derived from the opposite ends of cDNA Ku80-6 hybridized with several nonoverlapping restriction fragments from human leukocyte DNA, indicating that the gene encoding the 80-kDa Ku polypeptide is divided into several exons by intervening sequences. PMID- 2308939 TI - Zones of sharp genetic change in Europe are also linguistic boundaries. AB - A newly elaborated method, "Wombling," for detecting regions of abrupt change in biological variables was applied to 63 human allele frequencies in Europe. Of the 33 gene-frequency boundaries discovered in this way, 31 are coincident with linguistic boundaries marking contiguous regions of different language families, languages, or dialects. The remaining two boundaries (through Iceland and Greece) separate descendants of different ethnic or geographical provenance but lack modern linguistic correlates. These findings support a model of genetic differentiation in Europe in which the genetic structure of the population is determined mainly by gene flow and admixture, rather than by adaptation to varying environmental conditions. Of the 33 boundaries, 27 reflect diverse population origins at often distant locations. Language affiliation of European populations plays a major role in maintaining and probably causing genetic differences. PMID- 2308938 TI - DNA amplification is rare in normal human cells. AB - Three types of normal human cells were selected in tissue culture with three drugs without observing a single amplification event from a total of 5 x 10(8) cells. No drug-resistant colonies were observed when normal foreskin keratinocytes were selected with N-(phosphonacetyl)-L-aspartate or with hydroxyurea or when normal mammary epithelial cells were selected with methotrexate. Some slightly resistant colonies with limited potential for growth were obtained when normal diploid fibroblast cells derived from fetal lung were selected with methotrexate or hydroxyurea but careful copy-number analysis of the dihydrofolate reductase and ribonucleotide reductase genes revealed no evidence of amplification. The rarity of DNA amplification in normal human cells contrasts strongly with the situation in tumors and in established cell lines, where amplification of oncogenes and of genes mediating drug resistance is frequent. The results suggest that tumors and cell lines have acquired the abnormal ability to amplify DNA with high frequency. PMID- 2308940 TI - Regeneration of a functional RNA virus genome by recombination between deletion mutants and requirement for cowpea chlorotic mottle virus 3a and coat genes for systemic infection. AB - RNAs 1 and 2 of the tripartite cowpea chlorotic mottle virus (CCMV) genome are sufficient for RNA replication in protoplasts, whereas systemic infection of cowpea plants additionally requires RNA3, which encodes the 3a noncapsid protein and coat protein. By using biologically active CCMV cDNA clones, we find that deletions in either RNA3 gene block systemic infection. Thus, though some plant RNA viruses are able to spread systemically without encapsidation, both the coat and 3a genes are required for systemic infection of cowpeas by CCMV. When plants were coinoculated with CCMV RNAs 1 and 2 and both the 3a and coat deletion mutants of RNA3, 30-60% rapidly developed systemic infection. Progeny RNA recovered from systemically infected leaves in such infections contained neither of the starting deletion mutants but rather a single full-length RNA3 component with both genes intact. Nucleotide substitutions introduced into the coat protein deletion mutant as an artificial marker were recovered in the full-length progeny RNA, confirming its recombinant nature. Intermolecular RNA recombination in planta can, therefore, rescue a complete infectious genome from coinoculated mutants independently disabled for systemic spread. These results have implications for the repair of defective genomes produced by frequent natural replication errors, the possible emergence of newly adapted RNA viruses upon coinfection of new hosts, and further studies of RNA virus recombination. PMID- 2308941 TI - Modulation of constitutive cytochrome P-450 expression in vivo and in vitro in murine keratinocytes as a function of differentiation and extracellular Ca2+ concentration. AB - A procedure was developed for the per cell estimation of cytochrome P-450 dependent monooxygenase activities in cultures and whole cell suspensions of murine epidermal keratinocytes (MEKs). Murine keratinocytes cultured in medium containing less than or equal to 0.04 mM Ca2+ can be induced to differentiate by raising medium Ca2+ concentrations to 1.2 mM. The per cell activities of the monooxygenases 7-ethoxyresorufin O-deethylase (7-ER) and 7-ethoxycoumarin O deethylase (7-EC) were elevated greater than or equal to 2090% and approximately 460%, respectively, within 13-24 hr of Ca2+ shift. These increases could be completely suppressed by supplementation of culture medium with actinomycin D or cycloheximide immediately prior to Ca2+ shift. After prolonged culture in low Ca2+ medium, some MEKs detached from the monolayer. These detached cells had the characteristics of differentiating MEKs but did not have elevated 7-EC or 7-ER activities. Percoll gradient centrifugation of freshly isolated dorsal skin MEKs was used to prepare four subpopulations that differed in their stages of terminal differentiation. 7-EC and 7-ER activities varied among these subpopulations and correlated with the degree of MEK differentiation. Specifically, the lowest and highest per cell activities (greater than 7-fold difference) were in the basal and most differentiated spinous cell populations, respectively. Collectively, the current studies demonstrate that in vivo P-450 activities are markedly different in proliferating and differentiating MEKs and suggest that constitutive P-450 expression may be modulated as a function of changes in Ca2+ concentration that occur during keratinocyte terminal differentiation. PMID- 2308942 TI - The same target sequences are differentially important for activation of the interleukin 2 receptor alpha-chain gene in two distinct T-cell lines. AB - High-affinity receptors for interleukin 2 (IL-2) are expressed on T cells following activation. These receptors are composed of both alpha and beta chains. Expression of alpha chains and, therefore, expression of high-affinity receptors are critically regulated at the level of transcription initiation. We have further dissected the regulatory elements involved in controlling transcription of the IL-2 receptor alpha-chain (IL-2R alpha) gene. The IL-2R alpha promoter contains a kappa B site and binding sites for additional nuclear factors within a 50-base-pair region (positions -290 to -240 relative to the major transcription start site). These include one upstream of the kappa B site and one similar to the c-fos serum response element (SRE), which is downstream of the kappa B site. Mutation of the kappa B site decreases IL-2R alpha promoter activity in MT-2 cells (a T-cell line that has been transformed with human T-cell lymphotropic virus type I), but not in Jurkat cells (a T-cell leukemia line) that have been activated by phorbol 12-myristate 13-acetate (PMA). In contrast, mutation of a region upstream of the kappa B site decreases activity in PMA-induced Jurkat cells but increases activity in MT-2 cells. Mutation of the SRE-like site decreases activity in both cell types but the effect in PMA-induced Jurkat is more pronounced. Thus, these distinct cis-acting elements play different physiological roles in IL-2R alpha gene activation in MT-2 cells and PMA-induced Jurkat T cells. These studies provide direct evidence for a functionally significant SRE-like sequence in a gene other than c-fos and the actin genes and identify other elements that are critical for IL-2R alpha gene expression. PMID- 2308943 TI - Allelic diversification at the class II DQB locus of the mammalian major histocompatibility complex. AB - The allelic diversity at HLA class II loci either arose after the divergence of hominoid lineages or, alternatively, the polymorphism was present before speciation and has been maintained by selection. Here, we report the use of oligonucleotide primers to amplify, by the polymerase chain reaction, and sequence the polymorphic second exon of the DQB locus from 11 species, spanning more than 40 million years of mammalian evolution. Phylogenetic analysis reveals that of the four human DQB allelic types (DQB1-B4), three (DQB1-3) were found in chimpanzee and gorilla and two (DQB3 and -4) were identified in the rhesus monkey, suggesting that some of these types are 5-20 million years old. The ratio of replacement to silent substitutions was calculated between members of the same allelic type from different species. These results suggest that the evolution of the DQB3 allelic type is more constrained than that of the DQB1 allelic type; both evolve more slowly than the DXB locus, a linked but presumably nonexpressed locus. Further, the clustering of allelic subtypes by species in the phylogenetic tree indicates that allelic diversification has occurred subsequent to the divergence of hominoids. Finally, some haplotype combinations of DQA and DQB alleles are common to several hominoid species and may have been maintained for at least 5 million years. PMID- 2308944 TI - Magnesium dietary intake modulates blood lipid levels and atherogenesis. AB - In this study, we have examined the effects of variation in dietary Mg on the atherogenic process. Oral supplementation of rabbits fed a high cholesterol diet (1% or 2%) with the Mg salt magnesium aspartate hydrochloride (Magnesiocard) (i) lowers the level of serum cholesterol and triglycerides in normal (25-35%) as well as atherosclerotic (20-40%) animals and (ii) attenuates the atherosclerotic process markedly. In addition, we found that dietary deficiency of Mg augments atherogenesis markedly and stimulates (or activates) macrophages of the reticuloendothelial system. Evidence is presented to indicate that the hypercholesterolemic state may cause the loss of Mg from soft tissues to the serum, thereby masking an underlying Mg deficiency. PMID- 2308945 TI - Observation of single influenza virus-cell fusion and measurement by fluorescence video microscopy. AB - We have used intensified video fluorescence microscopy and digital image processing to observe and quantitate influenza virus (A/PR8/34/H1N1) fusion to human erythrocyte membranes. Viruses labeled with the lipid probe octadecylrhodamine B (R18) were seen to undergo fluorescence dequenching and eventual disappearance after exposure to pH levels known to induce virus-cell membrane fusion. Quantitative intensity measurements of single individual particles were possible. From these fluorescence data it has been possible to calculate the fraction of R18 dye molecules transferred from the virus to the cell. The redistribution of the lipid probe upon fusion at pH 5.0 had a t1/2 of 46 s, longer than expected for a free-diffusion model. The R18 loss was approximately twice as fast at pH 5.0 as at pH 5.1. No obvious delay until the start of fluorescence dequenching was observed after the pH changes, suggesting that activation processes are faster than the time resolution, 1-5 s, of the current method. PMID- 2308946 TI - Schwann cells promote the survival of rat retinal ganglion cells after optic nerve section. AB - Schwann cells (SCs) are known to play an important role for the regeneration of mammalian peripheral nerves. Their effect is likely due to the production of neuronotrophic and/or supportive factors. Here we study the effect of intraocular transplant of SCs on the survival of rat retinal ganglion cells (RGCs) after the intracranial section of the optic nerve. SCs were injected intraocularly in adult hooded rats. Surviving RGCs were retrogradely labeled with horseradish peroxidase applied to the proximal stump of the optic nerve. Results show that intraocular transplants of SCs promote the survival of a large number of RGCs for periods as long as 9 and 14 weeks after optic nerve section. In experimental retinae, surviving RGCs were 2- to 8-fold more numerous than in controls. This finding suggests that SCs are the source of factors that promote the survival of RGCs. Nerve growth factor is produced by SCs, and the intraocular injection of nerve growth factor has been previously shown to promote RGC survival. The rescuing effect of SCs on RGCs is greater than that obtained by intraocular injection of nerve growth factor. This greater effect may be due to the action of other neurotrophic factors produced by SCs or by transplanted SCs producing NGF in a sustained fashion. PMID- 2308947 TI - "Collective coding" of correlated cone signals in the retinal ganglion cell. AB - The signals in neighboring cones are partially correlated due to local correlations of luminance in the visual scene. By summing these partially correlated signals, the retinal ganglion cell improves its signal/noise ratio (compared to the signal/noise ratio in a cone) and expands the variance of its response to fill its dynamic range. Our computations prove that the optimal weighting function for this summation is dome-shaped. The computations also show that (assuming a particular space constant for the correlation function) ganglion cell collecting area and cone density are matched at all eccentricities such that the signal/noise ratio improves by a constant factor. The signal/noise improvement factor for beta ganglion cells in cat retina is about 4. PMID- 2308948 TI - Isothermal, in vitro amplification of nucleic acids by a multienzyme reaction modeled after retroviral replication. AB - A target nucleic acid sequence can be replicated (amplified) exponentially in vitro under isothermal conditions by using three enzymatic activities essential to retroviral replication: reverse transcriptase, RNase H, and a DNA-dependent RNA polymerase. By mimicking the retroviral strategy of RNA replication by means of cDNA intermediates, this reaction accumulates cDNA and RNA copies of the original target. Product accumulation is exponential with respect to time, indicating that newly synthesized cDNAs and RNAs function as templates for a continuous series of transcription and reverse transcription reactions. Ten million-fold amplification occurs after a 1- to 2-hr incubation, with an initial rate of amplification of 10-fold every 2.5 min. This self-sustained sequence replication system is useful for the detection and nucleotide sequence analysis of rare RNAs and DNAs. The analogy to aspects of retroviral replication is discussed. PMID- 2308949 TI - HLA- and H-2-associated variations of intra- and extracellular magnesium content. AB - Erythrocyte and plasma magnesium (EMg, PMg) levels have been shown to be genetically controlled in human and mouse. The possible association of these genetic factors with the major histocompatibility complex (MHC) (HLA and H-2) was investigated. Among unrelated adult male blood donors, HLA-B35 carriers have PMg (P less than 0.01) and EMg (P less than 0.0005) levels lower than those of noncarriers, while HLA-B38 carriers exhibit a significant (P less than 0.05) increase of both PMg and EMg levels when compared to the other individuals. Furthermore, HLA identical sibs have EMg values more similar than those of HLA different sibs. In the mouse, erythrocyte (P less than 0.001), plasma (P less than 0.001), liver (P less than 0.03), and spleen (P less than 0.04) Mg contents vary significantly according to H-2, with higher values being found in H-2k than in H-2q or H-2b congenic strains. However, non-MHC genes also have an influence on erythrocyte (P less than 10(-10], plasma (P less than 10(-10], spleen (P less than 10(-5], and kidney (P less than 10(-6] Mg contents as shown by differences between H-2 identical strains, which differ by the C3H and B10 genetic backgrounds. In conclusion, genetic factors controlling intra- and extracellular Mg levels are composed of at least three components: MHC (HLA and H-2)-associated genes, non-MHC genes, and tissue factors modulating the respective importance of the first two sets of factors. The mechanisms underlying this genetic system are discussed. PMID- 2308950 TI - Physical mapping of a low-copy DNA sequence in rye (Secale cereale L.). AB - A 900-base-pair (bp) sequence from a cDNA clone of the rye endosperm-storage protein gene Sec-1 was labeled with biotin and hybridized to Secale cereale 'Blanco' chromosomes. Hybridization was seen on the satellite part of the short arm of chromosome 1R, where the Sec-1 gene has been genetically mapped, in approximately 8.5% of the cells analyzed. The clone cross-hybridized at a lower frequency to rye chromosome arms 1R (long) (4.4%) and 2R (short) (2.6%), where two additional rye storage-protein loci, Sec-3 and Sec-2, respectively, have been mapped. A fourth hybridization site was observed on the short arm of chromosome 6R at a frequency of 3.0%. The cross-hybridization is attributed to a combination of residual sequence homology between the protein loci and the low-stringency conditions used in in situ hybridization. In situ hybridization mapping, in combination with chromosome walking by using molecular techniques, is suggested as an excellent approach to physical mapping of chromosomes. PMID- 2308952 TI - Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. AB - Enzyme replacement has been under consideration as a therapeutic strategy for patients with Gaucher disease for more than two decades. Previous studies indicated that single injections of purified glucocerebrosidase reduced the amount of storage material in the liver. It was important to determine whether administration of exogenous enzyme on a regular basis would be of clinical benefit. We report here that weekly i.v. infusions of a macrophage-targeted preparation of human placental glucocerebrosidase in a child with type 1 Gaucher disease increased hemoglobin from 6.9 +/- 0.8 g/dl (+/- 1 SD) to 10.2 +/- 0.4 g/dl (+/- 1 SD) over a 20-week period. The platelet count also increased from a pretreatment value of 30,000 +/- 7000/mm3 (+/- 1 SD) to 54,000 +/- 11,000/mm3 (+/ 1 SD). Phagocytic activity in the spleen decreased during the period of enzyme administration, and there was radiographic evidence of skeletal improvement. These observations document objective clinical responses to enzyme supplementation in a patient with a sphingolipid storage disorder. PMID- 2308951 TI - Biochemical identification of glycosylation inhibiting factor. AB - Rat monoclonal antibody against mouse glycosylation inhibiting factors was obtained, and radiolabeled glycosylation inhibiting factors from the mouse T-cell hybridoma, 231F1 cells, were purified by using the monoclonal antibody and antilipomodulin antibody. Analysis of the affinity-purified lymphokine by PAGE demonstrated two proteins of 14.4 kDa and 41 kDa. Both proteins migrated similarly under the reduced and unreduced conditions, indicating that each of the two species consist of a single polypeptide chain. Biologic activity of the lymphokine was recovered by extraction of the proteins from gel slices followed by renaturation. Evidence was obtained that suggested the 14.4-kDa peptide was a degradation product of the 41-kDa molecules. The 14.4-kDa peptide was also recovered by extraction of the surface-labeled 231F1 cells with Ca2+ chelator, indicating that the glycosylation inhibiting factor is associated with the cell surface. PMID- 2308953 TI - Limited sequence heterogeneity among biologically distinct human immunodeficiency virus type 1 isolates from individuals involved in a clustered infectious outbreak. AB - Human immunodeficiency virus type 1 isolates were obtained over a 3-year period from blood, brain, and lung of three patients in a clustered infectious outbreak. This included a blood donor who was initially asymptomatic but subsequently developed AIDS-related complex and two neonatal transfusion recipients who developed AIDS. Isolates from brain and lung replicated to greater than 30-fold higher levels in primary monocyte cultures than did those from blood; no growth differences on primary lymphocytes were observed. Thirteen clones were obtained from seven isolates, and env sequences were determined. The predicted amino acid sequences among these clones differed by only 0.01% but differed by 15-27% when compared to previously sequenced isolates from other patients. The level of envelope amino acid sequence divergence noted among these isolates is considerably lower than that previously reported for other human immunodeficiency virus isolates. No differences in the envelope unique to lung or brain isolates compared to blood isolates were noted. This study provides evidence that mutations in the envelope may not be necessary for disease progression and that other portions of the viral genome may contribute to cell-specific tropism. PMID- 2308954 TI - Cannabinoid receptor localization in brain. AB - [3H]CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9 tetrahydrocannabinol are not lethal. PMID- 2308955 TI - Structural analysis of the (dA)10.2(dT)10 triple helix. AB - The existence of DNA triple helices in vitro has been known for some time. Recent evidence suggesting that DNA triplexes exist in vivo and showing their potential for chemotherapeutic applications has renewed interest in these triple-strand conformations. However, little structural information is currently known about these unusual nucleic acid forms. We have induced and stabilized triple-helical (dA)10.2(dT)10 with MgCl2 at neutral pH. UV mixing curves demonstrate a 1:2 (dA)10 to (dT)10 stoichiometry at suitable MgCl2 concentrations. Thermal denaturation profiles establish a melting mechanism characterized by the initial loss of the third strand, followed by dissociation of the remaining duplex. The circular dichroic spectrum of the triplex form is distinct from that of a duplex equimolar in (dA)10. NMR studies show that magnesium-induced triplex formation is accompanied by an upfield shift of several imino proton resonances present before stabilization of the triplex form with MgCl2 and the induction of new upfield imino proton resonances. Nuclear Overhauser effect spectroscopy measurements on both undeuterated and C8--H-deuterated (dA)10.2(dT)10 triplexes demonstrate dipolar contacts between resolvable imino proteins and both adenine C8--H and C2- H aromatic protons. Hence, MgCl2 stabilizes a triplex structure in which thymine N3--H imino protons are involved in both Watson-Crick and Hoogsteen base pairing. PMID- 2308956 TI - A single chicken oocyte plasma membrane protein mediates uptake of very low density lipoprotein and vitellogenin. AB - Specific cell-surface receptors mediate the uptake of plasma proteins into growing oocytes of oviparous species, thereby forming yolk. Quantitatively the most important yolk precursors are the lipoproteins, very low density lipoprotein, and vitellogenin. We show that a single major chicken oocyte plasma membrane protein with an apparent molecular mass of 95 kDa as determined by SDS/PAGE under nonreducing conditions is the receptor for both of these ligands. Binding activities for the two ligands copurified on ligand affinity matrices and were inhibited by the same antibody preparations, and the ligands competed with each other for binding to the 95-kDa protein. In addition to these biochemical and immunological lines of evidence for the identity of the vitellogenin receptor with the very low density lipoprotein receptor, genetic proof was obtained. We have previously shown that the mutant nonlaying "restricted-ovulator" hen carries a defect in the gene responsible for functional expression of the oocyte 95-kDa protein. Here we demonstrate that this single gene defect in the restricted ovulator hen has detrimental consequences for the binding not only of very low density lipoprotein but also of vitellogenin to the 95-kDa receptor normally present in oocytes. The intriguing bifunctionality of this chicken oocyte membrane protein possibly relates to its crucial role in receptor-mediated control of oocyte growth. PMID- 2308957 TI - Pahhph-5: a mouse mutant deficient in phenylalanine hydroxylase. AB - Mutant mice exhibiting heritable hyperphenylalaninemia have been isolated after ethylnitrosourea mutagenesis of the germ line. We describe one mutant pedigree in which phenylalanine hydroxylase activity is severely deficient in homozygotes and reduced in heterozygotes while other biochemical components of phenylalanine catabolism are normal. In homozygotes, injection of phenylalanine causes severe hyperphenylalaninemia and urinary excretion of phenylketones but not hypertyrosinemia. Severe chronic hyperphenylalaninemia can be produced when mutant homozygotes are given phenylalanine in their drinking water. Genetic mapping has localized the mutation to murine chromosome 10 at or near the Pah locus, the structural gene for phenylalanine hydroxylase. This mutant provides a useful genetic animal model affected in the same enzyme as in human phenylketonuria. PMID- 2308958 TI - Charge isoforms of the adrenocortical pregnenolone-binding protein: influence of phosphorylation on isoformation and binding activity. AB - Isoelectric focusing of the Mr 34,000 pregnenolone-binding protein (PBP) isolated from the guinea pig adrenal cortex has revealed multiple charge isoforms. Alkaline phosphatase treatment resulted in the disappearance of the pI 5.4 isoform associated with the appearance of pI 5.9 and pI 6.1 isoforms; this alteration in the charge-isoform pattern of the PBP correlated with a loss in pregnenolone-binding activity. This finding appears to be novel for intracellular steroid-binding proteins and has not been demonstrated for steroid receptors, a well-studied group of phosphoproteins. Resolution of the PBP by nondenaturing polyacrylamide gel electrophoresis produced two radioactive peaks of [3H]pregnenolone in an equilibrium system, while only one peak was present in a nonequilibrium system, suggesting high- and low-binding affinity forms of PBP. Isoelectric focusing of highly purified PBP resolved multiple forms of Mr 34,000 proteins with pI values ranging from 6.4 to 5.2. Two of the Mr 34,000 charge isoforms were isolated, and each was used to generate polyclonal antibodies; both antisera were crossreactive against all forms of Mr 34,000 PBP. Western blot analysis revealed that the PBP was present in both the fasciculata and reticularis of the adrenal cortex, though the isoform patterns were not identical for the two zones. Additionally, the pregnenolone-binding activity was approximately 10-fold greater in the zona reticularis. In vitro alkaline phosphatase treatment of the PBP abolished pregnenolone-binding activity and caused an alteration in the charge-isoform pattern for PBP in the zona reticularis, where pregnenolone binding is high, to resemble the pattern found for the zona fasciculata, where pregnenolone binding is low. The results indicate that phosphorylation/dephosphorylation regulates pregnenolone-binding activity and influences the pattern of the PBP isoformation. The data further suggest that the pI 5.4 isoform may be the active steroid-binding molecule. PMID- 2308959 TI - Two-locus autosomal sex determination: on the evolutionary genetic stability of the even sex ratio. AB - In two-locus models of sex determination, there are two kinds of interior (polymorphic) equilibria. One class has the even sex ratio, and the other has equal allele frequencies in the two sexes. Equilibria of the second class may exhibit linkage disequilibrium. The condition for external stability of these second-class equilibria to invasion by a new allele is that the appropriately averaged sex ratio near the equilibrium be moved closer to the even sex ratio than the average among the resident genotypes. However, invasion by a new chromosome depends on the recombination fraction in a way that appears to preclude general results about the evolutionary genetic stability of the even sex ratio in this situation. PMID- 2308960 TI - Components of fitness become effectively neutral in equilibrium populations. AB - If, because of trade-offs or similar considerations, components of fitness are negatively correlated in equilibrium populations, they may then exhibit no correlation with total fitness. Lack of correlation with fitness is a fundamental characteristic of selective neutrality. Hence, selectively important traits become subsumed under neutral traits when the definition of neutrality is extended to include factors (genetic or phenotypic) that "behave as if they are neutral." PMID- 2308961 TI - Nuclear myxovirus-resistance protein Mx is a minor histocompatibility antigen. AB - Minor histocompatibility antigens (MiHAgs) cause slow-to-rapid organ transplant rejection by immunocompetent hosts and mild-to-severe graft-versus-host reactions in immunosuppressed hosts. MiHAgs are allelic forms of major histocompatibility complex (MHC) class I-restricted self-antigens recognized by cytotoxic T cells and usually are defined immunogenetically. Although structurally not identified as yet, it is assumed that MiHAgs are internal cell antigens that are processed and then presented by MHC class I proteins similar to viral antigens. To define a MiHAg both molecularly and functionally, we took advantage of the allelic difference of the structurally characterized intracellular myxovirus-resistance protein (Mx) and investigated its antigenicity. Skin grafts from congenic Mx+ mice carrying the functional Mx1 gene were rejected by mice lacking a functional Mx1 gene (Mx- mice). In parallel, cytotoxic MHC class I-restricted effector T cells specific for Mx protein and the H-2Kk antigen (but not for several other allelic H-2 antigens) were strongly induced in Mx- mice immunized with spleen cells from interferon-treated Mx+ mice. These data show that allelic forms of cell internal proteins presented by MHC class I may act as MiHAgs. PMID- 2308962 TI - Nonsense mutation in the glycoprotein Ib alpha coding sequence associated with Bernard-Soulier syndrome. AB - Three distinct gene products, the alpha and beta chains of glycoprotein (GP) Ib and GP IX, constitute the platelet membrane GP Ib-IX complex, a receptor for von Willebrand factor and thrombin involved in platelet adhesion and aggregation. Defective function of the GP Ib-IX complex is the hallmark of a rare congenital bleeding disorder of still undefined pathogenesis, the Bernard-Soulier syndrome. We have analyzed the molecular basis of this disease in one patient in whom immunoblotting of solubilized platelets demonstrated absence of normal GP Ib alpha but presence of a smaller immunoreactive species. The truncated polypeptide was also present, along with normal protein, in platelets from the patient's mother and two of his four children. Genetic characterization identified a nucleotide transition changing the Trp-343 codon (TGG) to a nonsense codon (TGA). Such a mutation explains the origin of the smaller GP Ib alpha, which by lacking half of the sequence on the carboxyl-terminal side, including the trans-membrane domain, cannot be properly inserted in the platelet membrane. Both normal and mutant codons were found in the patient, suggesting that he is a compound heterozygote with a still unidentified defect in the other GP Ib alpha allele. Nonsense mutation and truncated GP Ib alpha polypeptide were found to cosegregate in four individuals through three generations and were associated with either Bernard-Soulier syndrome or carrier state phenotype. The molecular abnormality demonstrated in this family provides evidence that defective synthesis of GP Ib alpha alters the membrane expression of the GP Ib-IX complex and may be responsible for Bernard-Soulier syndrome. PMID- 2308965 TI - Recent advances in hemophilia care. Proceedings of a symposium. Los Angeles, April 13-15, 1989. PMID- 2308963 TI - Habituation in the single cell: diminished secretion of norepinephrine with repetitive depolarization of PC12 cells. AB - Neuronally differentiated PC12 cells secrete decreasing amounts of [3H]norepinephrine when repetitively stimulated by depolarizing concentrations of potassium ion. The decreasing response shows attributes that have been classically ascribed to response habituation, a behavior commonly observed in nervous systems but found here in a homogeneous cell type. Alteration of the habituation pattern was caused by activators of the protein kinase C pathway and of voltage-gated calcium channels. PMID- 2308964 TI - The molecular basis of hemophilia A (factor VIII deficiency) in man; progress report from the Johns Hopkins University Hemophilia Project. PMID- 2308966 TI - Prenatal diagnosis of hemophilia in the United States. PMID- 2308967 TI - A review of clinical studies evaluating the efficacy of HIV inactivation methods. AB - Seroconversion surveillance is informative and must be continued. The level of safety is now so high that individual candidate cases of seroconversion need exquisite investigation to exclude the possibility of another source of the HIV infection. Consequently, we must be mindful that the inappropriate assignment of an HIV seroconversion incident to a blood product not only misrepresents the risk associated with currently available blood products, but may unfairly and devastatingly damage the reputation of a necessary and precious biological product. Inappropriate anxiety about a product, with resultant abandonment of its therapeutic benefit, may drastically reduce available factor concentrates, encourage price escalations associated with shortages, and lead unsettled patients to reduce their levels of prescribed therapy--with life threatening consequences. By monitoring the HIV-antibody testing records for all collection sites of a company's source plasma procurement network, the number and percent of donors found to be confirmably HIB-antibody positive might provide a clue to possible changes in the level of the undetected virus burden introduced into the source plasma supply. However, the combined efforts to develop higher purity products, combined with stringent inactivation methods has resulted in a product mix in use in the U.S. and elsewhere that seems to carry a risk of HIV seroconversion of less than 1 per 1000 patient-years of therapy. PMID- 2308968 TI - Arthroscopy of the knee in hemophilia. AB - Arthroscopic synovectomy for chronic hemophilic arthropathy has been performed since June of 1980, giving a 4 to 8 year follow-up of eight knees. The procedure was very successful in decreasing the incidence of hemarthroses. Only one patient had a recurrence of bleeding with synovitis. Joint flexion and extension returned to the preoperative status or improved in five knees. Only one patient lost significant motion. This loss occurred secondary to postoperative complications. Although arthroscopic synovectomy proved to be effective in synovial removal and decreasing the incidence of recurrent hemarthroses, the problem of postoperative bleeding with potentially very serious sequelae must be considered a very real threat to a successful result. PMID- 2308969 TI - The hemophilic pseudotumor. PMID- 2308970 TI - Evolution of methods for carrier detection in hemophilia. PMID- 2308971 TI - Hemophilia care in the near future. PMID- 2308972 TI - Perspectives in marrow purging. PMID- 2308973 TI - Purging leukemia remission marrows with alkyl-lysophospholipids, preclinical and clinical results. AB - Alkyl-lysophospholipids are unique compounds which have selective anti-cancer activity with relative sparing of normal bone marrow stem cells. Thus, they would appear to be ideal candidates for marrow purging. In contrast to most anti-cancer drugs, these compounds act on the cell membrane resulting in inhibition of phosphatidylcholine biosynthesis. In addition, these compounds inhibit protein kinase C activity and may interfere with signal transmission. In low doses in in vitro systems, they have been shown to induce differentiation in leukemic cell lines. Lethally irradiated Balb/c mice were injected with normal bone marrow cells containing 1-2% leukemic cells (WEHI III-B) to simulate a remission marrow after the cells were incubated in vitro for 24 hours with 0-100 ug/ml of 1-0 octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (ALP). All the mice given cells not treated with ALP succumbed to leukemia, whereas there was a dose-response increase in survival in those given ALP treated cells. Similar results were observed when the cells were cryopreserved and thawed before injection. Very little effect of ALP was noted on stem cells as measured by the spleen colony assay. In vitro studies using human marrow progenitor assays (CFU-GEMM) were undertaken in which marrow was mixed with 0.1% HL60 cells and exposed for 1 or 4 hours to ALP at 0, 25 and 50 ug/ml. The cells were plated and assayed for CFU GEMM and leukemic colonies. At 50 ug/ml, HL60 colonies were eliminated and there was no significant reduction in normal marrow progenitor cells. Clinical trials were initiated. Eleven patients with acute leukemia in remission who were candidates for autologous bone marrow transplantation had marrow harvested, incubated with 50 ug/ml of ALP and cryopreserved. CFU-GEMM assays before and after purging showed no differences. There was a similar significant reduction after cryopreservation regardless of whether marrows were purged. Two patients were transplanted with purged marrow, one in early relapse and one in a marrow remission, but had evidence of CNS leukemia. In both, ablative therapy consisted of cytosine arabinoside, 3 gm/m2 x 12 doses, followed by fractionated TBI to a total of 12 Gy prior to reinfusion of thawed marrow. The patient in early relapse had progression of leukemia by day 28. The patient in marrow remission is disease free 9 months after transplantation. These studies indicate that purging marrow with ALP is a promising approach and further clinical studies are indicated. PMID- 2308974 TI - Bone marrow purging and processing. Proceedings of the Second International Symposium on Bone Marrow Purging and Processing. Cancun, Mexico, April 27 and 28, 1989. PMID- 2308975 TI - Breast cancer and laser photoradiation therapy: an in vitro model for autologous bone marrow purging. PMID- 2308976 TI - Radioisotope-mediated purging in bone marrow transplantation. PMID- 2308977 TI - Lymphokine-activated killer (LAK) cell purging of bone marrow. AB - The in vitro incubation of NK cells with the lymphokine IL-2 stimulates the development of a population of activated cytotoxic lymphocytes (LAK cells). These activated cells have the capacity to recognize and kill a wide range of neoplastic cells. The cytotoxic activity of LAK cells does not appear to be directed against normal, non-neoplastic cells and we have recently examined the potential for using LAK cells as a method of purging bone marrow for autologous transplantation in patients with widespread neoplastic diseases. We have utilized an experimental system consisting of the incubation of LAK cells from inbred F344 rats and normal bone marrow and demonstrated that this procedure does not interfere with the ability of the treated bone marrow to reconstitute lethally conditioned recipients. The frequency and rate of reconstitution is the same in treatment and control groups, including incubation periods that extend up to 18 hours. When RNK-16 leukemia cell line (a spontaneous large granular lymphocyte leukemia that is syngeneic to the F344 strain) is added to the incubation mixture, the LAK cells have the ability in vitro to recognize the neoplastic cells and prevent the transmission of the leukemia to naive animals following bone marrow transplantation. As expected from the in vitro LAK cytotoxic activity, these activated cells are capable of recognizing and eliminating a variety of neoplasms. To date we have tested three different hematopoietic tumor lines derived from the F344 strain and one that was induced in an unrelated BN strain. In each case, the F344 LAK cells demonstrated an ability to prevent the transmission of a fatal leukemia and significantly prolong the survival of animals that had received larger numbers of neoplastic cells. The tumor lines examined included the RNK-16 line (NK cells), the Dunning leukemia (monocyte lymphoblastic leukemia), a T-lymphocyte lymphoma and the acute myelogenous leukemia of BN rats (BN AML). Comparison of the results of these purging experiments to those seen when control animals are injected with graded doses of the individual tumors indicate that the LAK cells are eliminating approximately 2 3 logs of neoplastic cells. The ability of LAK cells to kill a wide range of tumors without damage to the ability of the recipient stem cells to reconstitute the bone marrow may allow for an important application for this type of purging technique in patients with neoplasms for which specific immunological or chemical therapies do not exist. PMID- 2308978 TI - Purging in auto- and allografts: monoclonal antibodies which use human complement and other natural effector mechanisms. AB - CAMPATH-1M is a rat IgM monoclonal antibody which binds to an antigen on all human lymphocytes and monocytes, but which is not present on marrow stem cells (Hale et al., 1983). Lymphocytes can be efficiently killed in bone marrow buffy coat preparations using the antibody and donor human serum as a means to avoid graft versus host disease (GVHD) (Waldmann et al., 1984). An analysis of 520 matched sibling bone marrow transplants (BMT) for leukaemia demonstrates that T cell depletion using CAMPATH-1M markedly reduces the incidence and severity of GVHD, but there is an increased risk of graft rejection. In the case of CGL in chronic phase, there is also an associated extra risk of relapse, particularly in patients where engraftment may have been compromised (Hale et al., 1988a). A rat IgG2b antibody of the same specificity as CAMPATH-1 (CAMPATH-1G) was developed which is able to both fix human complement and opsonize lymphocytes in vivo (Dyer et al., 1989). Initial studies for the prophylaxis of bone marrow rejection in 55 mismatched and matched unrelated donor (MUD) BMTs suggest that CAMPATH-1G treatment of the recipient may reduce, but not eliminate, marrow graft rejection. The broad CAMPATH-1 specificity means that it is also ideal for purging a range of lymphoid malignancies prior to autologous BMT, or even for direct serotherapy of leukaemic patients. However, there may be limitations of monoclonal antibody purging using complement or other natural effector mechanisms either in vivo or in vitro; in particular, antigenic modulation and an antiglobulin response. Phase 1 studies of "in vivo purging" with a monovalent CD3 antibody (Clark et al., 1989), and also with a genetically engineered humanized IgG1 (CAMPATH-1H) (Hale et al., 1988b) suggest that these limitations can be overcome. PMID- 2308979 TI - Elimination of chemoresistant myeloma clonogenic cells from human bone marrow by monoclonal antibody and complement. AB - We examined the effectiveness of a previously characterized plasma cell-reactive monoclonal antibody (MoAb), MM4, in eliminating multi-drug resistant (MDR1) multiple myeloma (MM) clonogenic colony-forming cells (CCCs). MDR1 sublines with 6-fold (RPMI8226/DOX6) and 40-fold (RPMI 8226/DOX40) resistance to doxorubicin (DOX) were selected from the chemosensitive MM parent line RPMI 8226/S. Both sublines remained reactive with plasma cell MoAbs MM4 and PCA-1, as measured by flow cytometric immunophenotype analysis. MM4 and rabbit complement (C') were cytotoxic to MDR DOX6 (74 +/- 8.5%) and DOX40 (75 +/- 11.3%) cells as well as to chemosensitive 8226/S (80 +/- 5.6%) cells. Treatment with MM4 + C' depleted up to 3 logs of chemosensitive and MDR myeloma CCCs (8226/S: 99.26 +/- 0.52%; DOX6 99.91 +/- 0.08%' DOX40 99.15 +/- 0.55%). In addition, this approach abrogated the selfrenewing capacity of chemoresistant and MDR1 myeloma cell lines, according to doubling time analyses. By comparison, the P-glycoprotein-reactive MoAb MRK-16 and C' was effective in deleting MDR1 CCCs (DOX10: 95.71 +/- 2.51%; DOX40: 99.61 +/- 0.43%) but affected chemosensitive myeloma CCCs only slightly (5.93 +/- 14.52%). When DOX40 cells were mixed with normal bone marrow (BM) in a ratio of 10:90 (MM:BM), treatment with MM4 plus C' deleted MM CCCs (98.80 +/- 0.71%) without affecting the majority of normal BM progenitors. The combination of MM4 and MRK-16 did not enhance MDR myeloma CCC depletion. These observations suggest that MM4 + C' may be useful for depleting MDR as well as chemosensitive myeloma clonogenic cells from human bone marrow. PMID- 2308980 TI - Efficacy of bone marrow purging in AML using monoclonal antibodies and complement. PMID- 2308981 TI - Bone marrow purging with immunotoxins for treatment of T cell acute lymphoblastic leukemia (T-ALL). PMID- 2308982 TI - Pharmacological-mediated purging with mafosfamide in acute and chronic myeloid leukemias. The Italian Study Group. AB - The success of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) in complete remission (CR) is limited by the high relapse rate. It is generally accepted that minimal residual disease (MRD) plays a major role in determining the relapse of disease. In our study we investigated in adult acute leukemia and in chronic myelogenous leukemia (CML), the efficacy of ex vivo marrow purging with mafosfamide (an in vitro derivative of cyclophosphamide). We also describe an improved purging approach ("programmed method") based on the evaluation of sensitivity to the drug measured in each individual patient prior to ABMT. The analysis of clinical data in terms of disease-free survival (DFS) shows that the "programmed method" gives significantly better results than those obtained using the standard dose of mafosfamide (80% DFS in 18 AL patients vs. 44% in 33 ANLL patients and 33% in 56 ALL patients). The evaluation of the CR to purging interval in ALL and ANLL shows that a period of greater than 6 months is necessary to obtain longer DFS. Considering pre-transplant regimens, busulfan cyclophosphamide is more effective in ANLL, and cyclophosphamide-fractionated total body irradiation is the best treatment for ALL. The studies using mafosfamide marrow purging in CML demonstrate that the drug is able to achieve a decrease of the Ph1+ marker. Three patients who showed conversion of this cytogenetic marker have been autografted with interesting clinical results. PMID- 2308983 TI - Specific killing of neuroblastoma cells in vitro by immunotoxins. PMID- 2308984 TI - Persistent suppression of granulo-erythropoietic precursor cells in alpha interferon treated CML patients undergoing autologous stem cell transplantation: in vitro and clinical results. PMID- 2308985 TI - Elimination of clonogenic leukemic cells from bone marrow using monoclonal antibodies and magnetic immunobeads. PMID- 2308986 TI - Isolation of hemopoietic precursor cells from human marrow by negative selection using monoclonal antibodies and immunomagnetic beads. AB - A purified or enriched population of human marrow hemopoietic precursor cells may be produced by using a monoclonal antibody to specifically bind to the desired cell population (positive selection), or by removing undesired cell populations contaminating the mixture (negative selection). We describe a simple negative selection technique using commercially available monoclonal antibodies and immunomagnetic beads to produce a mononuclear marrow cell fraction which comprises no more than 2% of the initial cell population yet contains all the BFU E and CFU-GM present originally. This procedure is an efficient method for producing hemopoietic precursor cells appropriate for studying cell-substrate adhesions, homing mechanisms, and response to growth factors without interference by contaminating accessory cells. PMID- 2308987 TI - The efficiency of a new cell separation technique in bone marrow purging without damaging the purged tumor cells. PMID- 2308988 TI - Purging of myeloma cells from bone marrow using monoclonal antibodies and magnetic immunobeads in combination with 4-hydroperoxycyclophosphamide. PMID- 2308989 TI - Immunopharmacologic purging of breast cancer from bone marrow for autologous bone marrow transplantation. PMID- 2308990 TI - The use of immunorosettes for purging of bone marrow in childhood cancer. PMID- 2308991 TI - Density-gradient separation for 4-hydroperoxycyclophosphamide purging of autologous bone marrow grafts. AB - We studied density-gradient separation of autologous bone marrow grafts in preparation for ex vivo 4-hydroperoxy-cyclophosphamide (4-HC) purging. A two-step procedure of buffy coat isolation followed by Ficoll-diatrizoate separation was used. Buffy-coat cells were isolated primarily either using the COBE 2991 Blood Cell Processor or Haemonetics 30 Cell Separator. All density-gradient separations were performed using the COBE 2991. The nucleated cell recoveries after buffy coat isolation were 44.3 +/- 10.4% and 85.1 +/- 10.5% (+/- standard deviation, P less than 0.001) for the Haemonetics 30 and COBE 2991 isolated grafts, respectively. The final nucleated cell recoveries after density-gradient separation for these two buffy-coat techniques were 24.2 +/- 10.1% and 29.5 +/- 14.7% (p = 0.30). Compared to manual density-gradient separation, the techniques using the COBE 2991 recovered slightly higher numbers of nucleated cells and CFU GM. The red blood cell concentration of the 4-HC incubation mixture was 1.0 +/- 0.6% and the CFU-GM survival after treatment was 2.4 +/- 2.6%. The variability in CFU-GM survival after 4-HC incubation of the density-gradient separated grafts appears less than previous experience treating buffy-coat cells. Density-gradient separation of autologous bone marrow appears to provide a more uniform treatment with 4-HC and may improve the clinical transplant course of the autograft recipient. PMID- 2308992 TI - Automated isolation of mononuclear cells using the Fenwal CS3000 blood cell separator. AB - We describe a method for in vitro isolation of mononuclear cells from peripheral blood or bone marrow using a Fenwal CS3000 Apheresis device without employing density gradients or sedimenting agents. The automatic processing program requires minimal operator intervention and no subjective operator decisions. A mean of 67% of starting mononuclear cells were recovered in a 100 ml product having 95% mononuclear cells and less than 1% of the original red blood cells. The average processing time was 35 minutes. PMID- 2308993 TI - Bone marrow purging with glucocorticoids. PMID- 2308994 TI - A three-dimensional culture system for the growth of hematopoietic cells. AB - A physiological three-dimensional culture system was developed for the growth of human bone marrow. Bone marrow stromal cells were established on a nylon filtration screen template, suspended in liquid medium and grown to 70% confluence, and inoculated with hematopoietic cells. An intricate microenvironment is established to support hematopoiesis, which proceeds in a three-dimensional orientation. Analysis of the adherent zone of these cultures with flow cytometry and progenitor cell assays reveals multilineage hematologic expression and active proliferation of immature cells for the 12 week experimental period. Similar results were obtained with rat bone marrow cultures using this methodology. The suspended nylon mesh system is novel in that it supports the growth of several hematologic lineages concurrently. This system may lend itself to the growth of purged or untreated bone marrow for transplantation. PMID- 2308995 TI - Combination chemotherapy and verapamil to purge drug resistant leukemia cells from human bone marrow. PMID- 2308996 TI - Efficacy of T cell depletion of surgically resected cadaveric marrows by monoclonal antibodies: considerations in HLA-mismatched marrow transplantation. AB - The potential therapeutic benefits of allogeneic bone marrow transplantation (BMT) remain generally unavailable to patients who have diseases amenable to treatment by allogeneic BMT, but who lack an identifiable HLA-matched marrow donor. If graft versus host disease and graft rejection can be controlled, then the possibility of expanding allogeneic BMT to minimally HLA-matched or fully mismatched combinations exists and a "universal" donor marrow bank might be established. Towards this end, we have evaluated surgical harvest of cadaveric marrow, T cell depletion of such marrow (for prevention of graft-versus-host disease), influence of surgical harvest on final T cell content, and final cell yield. Marrow harvest was coordinated with the donation of other tissues or organs of cadaveric origin. In a series of twenty-two surgical vertebral body harvests, the initial marrow yield per vertebral body was 4.5 x 10(9) with four to six vertebral bodies per harvest. T cell depletion was evaluated by a limiting dilution assay. Since a combination of multiple monoclonal antibodies with specificity for T cell surface molecules provided greater reproducibility in the depletion of T cells from marrow than the utilization of any single antibody, a pool of monoclonal antibodies and complement were used to treat the marrow. The final cell yield per vertebral body was 2.1 x 10(9) for an average total yield of 9.3 x 10(9) cells per harvest. T cell content for each marrow following T cell depletion was less than 0.001%. These marrow have been cryopreserved as a bank of characterized donor marrow for use in HLA minimally matched or unmatched marrow transplantation. PMID- 2308997 TI - Gene transfer by electroporation: a model for gene therapy. AB - We examined electroporation for the introduction of DNA into hematopoietic cells in order to develop an in vitro model for human gene therapy. We demonstrated that electroporation is a relatively efficient and reproducible method of gene transfer in permanent hematopoietic lines. Characterization of DNA transfer revealed that genes are integrated in single or low copy number. We showed that human normal granulopoietic progenitors can express the transferred gene at a frequency of more than two percent. Although the progeny of erythroid progenitors failed to express transferred genes, the frequency of transfer to erythroid clones, as detected by the polymerase chain reaction, was moderately high (16%). In order to improve efficiency of expression, we examined the effect of different viral and cellular promoters in the hematopoietic lines K562 and KG1a as well as in marrow stromal cells. We found that Rous Sarcoma virus LTR was the most active promoter in K562 while the murine cytomegalovirus immediate early promoter was highly active in KG1a and marrow stromal cells. Further improvements in the efficiency of DNA transfer and expression with electroporation are likely to result in a successful hematopoietic model for gene therapy. PMID- 2308998 TI - Cryopreservation and storage of human bone marrow: a survey of current practices. AB - As bone marrow transplantation is being used with increasing frequency, problems of storage space and cost, inventory control and disposal have arisen. Issues such as maximum storage time and acquisition of consent for marrow disposal need to be addressed before a large inventory is accumulated. Consideration should also be given to using non-infused marrows for research purposes. Eighty-three bone marrow transplant centers were surveyed in an attempt to establish a data base with regard to guidelines for storage of cryopreserved human bone marrow. Fifty-two centers (62.7%) responded to the questionnaire, 5 of which did not have an active cryopreservation program. The remaining 47 centers freeze and store autologous marrow from patients with leukemia, lymphoma, neuroblastoma and a large diversity of other conditions including solid tumors. Twelve centers (25.5%) specify maximum storage times of up to 5 years, but only 9 centers (19.1%) require the donor to sign a specific consent form for marrow disposal if it is not used for transplantation within a given time. Eighty-five percent of the responding centers reinfuse at least half of the marrows they freeze within 12 months of harvesting. It appears that at least 90% of marrows that are being reinfused have been stored for three years or less. However, the storage time of non-infused marrows extends even further, and autologous marrow has been reinfused successfully as long as eight years after storage. PMID- 2308999 TI - Toxicity of autologous bone marrow graft infusion. AB - We prospectively evaluated infusion-related toxicities in 70 patients undergoing autologous bone marrow transplantation. We studied symptoms, vital signs, forced vital capacities, and serum chemistry changes associated with the infusion. The bone marrow grafts were cryopreserved in 10% dimethylsulfoxide (DMSO) and stored in liquid nitrogen. All grafts were concentrated by centrifugation and the buffy coat cells collected. Additionally, 20 grafts had mononuclear cells collected using density-gradients. Before infusion, the patients were medicated with hydration, mannitol, hydrocortisone, and diphenhydramine. The grafts were rapidly thawed and immediately infused without further manipulation. The mean volume infused to patients who received buffy-coat grafts was 6.3 +/- 1.7 ml/kg containing 0.7 +/- 0.2 gm/kg of DMSO. Patients who received density-gradient separated grafts received a product with a volume of 2.9 +/- 1.3 ml/kg containing 0.3 +/- 0.1 gm/kg DMSO. Symptoms included nausea, abdominal cramping, and flushing; patients who received buffy-coat grafts had more complaints. These patients also had mild increases in AST, ALT, and total bilirubin. Forced vital capacities were decreased in this group after the graft infusion; this change was not associated with the infusion of the density-gradient separated products. There was a significant difference (p less than 0.01) in heart rate and blood pressure changes associated with the infusions. Patients who received the larger product had a minimum heart rate of 63.3 +/- 12.4 BPM as compared to 80.7 +/- 18.0 BPM for the other patients. We found minor to moderate toxicities associated with the graft infusions, which were more severe in patients who received buffy coat grafts. This could have resulted from the greater amounts of DMSO, cell lysis products, or volumes infused. PMID- 2309000 TI - Transporting bone marrow for in vitro purging before autologous reinfusion. AB - We describe the procedures employed for transporting bone marrow to and from a central facility. Marrow has been harvested from 80 patients with neuroblastoma, at 16 centers which are geographically dispersed throughout North America. Marrow from the outside transplant centers was packed on wet ice or cold packs in insulated containers, and transported by commercial carriers or chartered aircraft to the central processing laboratory. Post processed marrows were frozen in liquid nitrogen and returned by commercial carrier to the referring institution. In comparing transported with non-transported but similarly treated marrows, no differences were found in any of the following parameters: (1) CFU-GM recovery, (2) fraction viable cells at thawing, or (3) time to engraftment in patients. We conclude the transportation of harvested marrows to a central purging facility is safe. Based on this experience, we propose a set of standards, which, if adhered to, will insure the continued safe processing, shipping, and storage of bone marrow in all centers so engaged. PMID- 2309001 TI - Combinations of 4-hydroperoxycyclophosphamide (4-HC) and cisplatin for bone marrow purging in autologous marrow transplantation: an update. AB - We are studying the usefulness of combinations of 4-HC and cisplatin as a potential purging regimen for autologous bone marrow transplantation. In all of our studies, in vitro cytotoxicity was determined by clonogenic assay, and drug interaction was quantitated using the multiple drug-effect analysis method. The cells were incubated for one hour (4-HC) and/or 4 hours (cisplatin). We found that the drugs in combination had cytotoxic synergism against human leukemia cell lines (K-562 and Raji). The synergism was sequence-dependent (cells must be exposed to 4-HC first), was present at various molar ratios of the drugs, and most pronounced at high levels of cell kill. We also found that the drugs had cytotoxic synergism against normal human marrow progenitors (CFU-GM). However, the leukemic cells were approximately 55 times more sensitive to the combination than CFU-GM. In a murine system, the drugs were synergistic against L1210 leukemia cells and normal murine CFU-GM, but L1210 cells were at least 130 times more sensitive to the combination than CFU-GM. To determine the ability of L1210 cells to grow in vivo after exposure to the drugs, BDF1 mice were injected with 2 x 10(4) cells which had been incubated with 4-HC and/or cisplatin. The survival time of untreated controls was 13 +/- 2.8 days. For treated groups, the cure rates after 50 days of observation were 33% (4-HC, 40 uM), 0% (cisplatin, 8 uM), and 100% (4-HC + cisplatin). Finally, at concentrations resulting in equivalent toxicity to marrow CFU-GM, cisplatin seemed to be more toxic to murine spleen blast colony forming cells (CFC-BC) than 4-HC. The drugs in combination appeared to have at least additive toxicities against CFC-BC. PMID- 2309002 TI - Selective eradication of leukemic (L-CFU) versus normal (CFU-GM) myeloid progenitors in suspension culture utilizing a prolonged exposure to 1-B-D arabinofuranosylcytosine (Ara-C) and deoxycytidine (dCyd). PMID- 2309003 TI - Effect of methylprednisolone and VP-16 on acute lymphocytic leukemia cells. PMID- 2309004 TI - Potassium channels: basic function and therapeutic aspects. Proceedings of the 29th annual A.N. Richards Symposium. Valley Forge, Pennsylvania, May 16-17, 1988. PMID- 2309005 TI - Comparison of K+ channels in mammalian atrial and ventricular myocytes. PMID- 2309007 TI - Biophysics of memory. PMID- 2309006 TI - K(+)-channel activators in vascular smooth muscle. PMID- 2309008 TI - Carbachol depolarizes and evokes an inward current in heart muscle: a novel action of muscarinic agonist. PMID- 2309009 TI - Measurement, block, and modulation of potassium channel currents in the heart. AB - The results with the K+ channel blocking compounds are encouraging because they show a slight structural change in a parent blocking compound can dramatically alter the type of K+ channel blocked by a drug. Our work continues in an effort to determine a more detailed relationship between structural features of a blocker and the type of K+ channel effected. We hope to be able to reveal the requirements for potent and specific blockers of each of these channel types. Selective blockade of these, and other, K+ channels in heart and smooth muscle cells, a goal suggested by the preliminary results presented here, may provide useful tools for more detailed studies of K+ channels. Our experiments also show that temperature can be used to separate the beta-adrenergic regulation of ICa and IDR suggesting different modulatory mechanisms. The results with forskolin show this separation exists at the level of elevated cAMP. This suggests that the K+ and Ca++ channel proteins may be phosphorylated by the same cAMP-dependent protein kinase but with different temperature-sensitive kinetics. It will be interesting to see if this temperature-sensitivity extends to phosphorylation of the channel during intracellular application of cAMP-dependent protein kinase. PMID- 2309010 TI - Evolution of subterranean mammals at the organismal and molecular levels. Proceedings of the Fifth International Theriological Congress. Rome, Italy, August 22-29, 1989. PMID- 2309011 TI - Brains of mole rats from Africa and North America. AB - The total brain size and quantitative brain composition have been analyzed in four bathyergids and two geomyids in comparison with those in two spalacids. These mole rats show encephalic features corresponding to their phyletic descent from the cricetids. Their diversity in brain organization suggests that, in spite of the seeming uniformity of their habitat the world over, they are narrowly adapted, a quantitative-to-qualitative relationship which only detailed eco ethological information will be able to explain. The special case of the naked mole rat raises once again the problem of distinguishing evolution from specialization and relating brain development to social life. PMID- 2309012 TI - Genetic diversity and its ecological correlates in nature: comparisons between subterranean, fossorial, and aboveground small mammals. AB - We have reanalyzed the levels of observed heterozygosity based on old and new material of small mammals in attempt to retest the environmental theory of genetic diversity or the niche-width variation hypothesis. This study involves old and new material of 184 small mammalian species both insectivores and rodents; 111 living aboveground and 73 species living partly (fossorial, N = 28) or totally (subterranean, N = 45) underground. The results indicated that (i) in general, insectivores harbor significantly lower levels of heterozygosity than rodents, and (ii) both overall, and in insectivores and rodents separately, the narrow-niche fossorial and subterranean species displayed significantly lower levels of observed heterozygosity than small mammalian species living aboveground. This is true in almost all parametric and nonparametric analyses. Subterranean and fossorial small mammals are more homozygous in protein diversity, primarily isozymes, compared with aboveground species. This pattern corroborates the environmental theory or niche-width variation hypothesis of genetic diversity. PMID- 2309013 TI - Ribonuclease in different chromosomal species of the mole rat, superspecies Spalax ehrenbergi: concentration in the pancreas and primary structure. AB - Ribonucleases are found in considerable quantities in the pancreas of a number of mammalian taxa and a few reptiles. The ribonuclease content varies greatly in different species. Large quantities are found in ruminants and species that have a ruminant-like digestion and in a number of species with coecal digestion. This is a response to the necessity of digesting large amounts of RNA derived from the microflora of the stomach of ruminants or species with ruminant-like digestion or of the coecum of species with coecal digestion. The amino acid sequence of pancreatic ribonuclease from the chromosomal species 2n = 60 of the mole rat, superspecies Spalax Ehrenbergi was determined. From the comparison of the sequence with those of other mammalian species we found that Spalax diverged from the myomorph rodent branch before the divergence of the Muridae (mouse, rat) from the Cricetidae (hamster, muskrat). Spalax ribonuclease shares several amino acid residues with other myomorph rodent species. These are not or only rarely observed outside this rodent suborder. Although the ribonuclease content varies greatly in different mammalian species, the variation in content between individuals within a species is small. Spalax is an exception to this with ribonuclease contents varying over more than an order of magnitude in different individuals. Ribonucleases isolated from the chromosomal species 2n = 52, 2n = 58 and 2n = 60 have identical elution positions on reversed-phase HPLC. The enzyme from the 2n = 54 species, however, elutes at a slightly earlier elution position. No amino acid sequence differences have been found hitherto between the ribonucleases of the four chromosomal species of Spalax ehrenbergi occurring in Israel. However, due to lack of material we were unable to determine more than about 20% of the sequence of the enzyme from the 2n = 54 species, which is the oldest offshoot. PMID- 2309015 TI - The thin red line. PMID- 2309014 TI - An M.D.-J.D.'s response to the medical malpractice crisis. PMID- 2309016 TI - To challenge the chess master. PMID- 2309017 TI - Discovering prevention: one chief's odyssey. PMID- 2309018 TI - Care for the dying--the end of a continuum. PMID- 2309019 TI - Past and present. The two faces of altruism. PMID- 2309020 TI - Ourselves and patients who are dying. PMID- 2309022 TI - Taking the high road. PMID- 2309021 TI - Fatal poisoning by cyclic antidepressants. AB - In a seven-year period (1979-1985), 151 fatal cases of poisoning by cyclic antidepressants were registered at the Institute of Forensic Chemistry in Copenhagen. Amitriptyline was by far the most frequently occurring compound. An increase in the number of fatal poisonings by cyclic antidepressants was seen over the seven years, also compared to the total number of fatal poisonings registered at the Institute in the same period. The increase was seen mostly in men, the number of women remaining fairly constant over the period. Altogether there were 91 women and 60 men. Most cases were found in the 30-39 age group closely followed by the 40-49 age group, both groups including twice as many women as men. Men dominated only in the 20-29 age group. One hundred and twenty one of the cases were found to be suicides, while thirteen of the cases were more dubious and were registered as "accident/suicide?" Seventeen of the cases were apparent accidents; of these, thirteen (76%) had a mention of alcohol abuse in their case histories. PMID- 2309023 TI - Deja vu all over again. PMID- 2309024 TI - On acquiring knowledge about people and the capacity to pretend: response to Leslie (1987) AB - Leslie (1987) has proposed a cognitivist model for the young child's "theory of mind" and capacity to pretend. Serious shortcomings in Leslie's nondevelopmental, nonsocial, and restrictively cognitive account are noted, and an alternative thesis is proposed: A young child's knowledge about people is grounded in the experience of affectively charged interpersonal relations, and the child's capacity for pretend play develops on the basis of prior abilities to perceive the nature of other people's relatedness to the world. Clinical phenomena associated with autism and congenital blindness provide evidence for this thesis. PMID- 2309025 TI - Prospects for a cognitive neuropsychology of autism: Hobson's choice. AB - Leslie (1987b) proposed a new, metarepresentational model for the cognition of pretense. This model identified a cognitive component necessary for the normal development of a "theory of mind." In this article, the relation of the child's early affective sensitivities to this component is considered. Early affective sensitivities seem to be cognitively distinct from the metarepresentational component. Childhood autism provides an interesting opportunity to study this problem. Three theoretical possibilities for the pathogenesis of this condition are presented: (a) a basic affective disorder as proposed by Hobson (this issue, p. 114), (b) a basic affective disorder and a basic cognitive disorder jointly, and (c) a basic cognitive disorder. There is little evidence for Option a, and a growing body of evidence supports Option c. Option b is sidelined for the time being on grounds of parsimony. Leslie's original theoretical proposals are revised, and some resulting implications are presented for the future investigation of the cognitive neuropsychology of autism. PMID- 2309026 TI - Gravitoinertial force versus the direction of balance in the perception and control of orientation. AB - Curthoys and Wade (1990) appeal to land-based data in defending the traditional view that stimulation of the otolith organs leads to perception of the direction of gravitoinertial force. However, such data do not permit rejection of the hypothesis that the perception of orientation is based on the dynamically defined direction of balance, which is qualitatively different from the kinetically defined direction of gravitoinertial force. Furthermore, the approach of Curthoys and Wade is compromised by their failure to consider relations between the perception and control of orientation. Such relations must be considered in developing a general theory of orientation. PMID- 2309027 TI - [Research activity in the psychosomatic medicine/psychotherapy specialty at West German universities--a 1978-1988 status report]. AB - The documentation of research activities in the discipline of psychosomatics/psychotherapy at the Federal German universities during the past 10 years includes scientific papers and monographs as well as research projects. In addition, a list of theses submitted by candidates wishing to qualify for lecturing at a German university ("Habi,-litationsschrift") has been set up for the same period. The emphasis is on psychosomatic/psychotherapeutic care, specific psychosomatic diseases and the management of chronic diseases, whereas less research activity was seen in the areas of psychophysiology and epidemiology. The data represent considerable research activity in this discipline, but it would be advisable to see to it that in the future such data are better documented and coordinated. PMID- 2309028 TI - [Typical combinations of personal satisfaction and their relation to symptoms, diagnosis and indications for therapy. II: Relation of personal satisfaction, symptoms and indications for psychotherapy]. AB - In our sample of psychotherapy outpatients (n = 562) age, gender and education do not influence satisfaction measured by questionnaire. Patients with low satisfaction showed more depressive symptoms, conflict reactions, psychotic/borderline symptoms and come into therapy more often. Patients with higher satisfaction showed to be more hysteric and had more psychosomatic symptoms. Indication for therapy depends more on (dis)satisfaction than on diagnosis. Dissatisfaction with a certain area affects indication for therapy less than statistically evaluated types of answers. Those types (satisfaction or dissatisfaction with all areas) are interpreted as a sign of psychological dedifferentiation. Satisfaction is a subjective phenomenon and does not depend on objective facts. PMID- 2309029 TI - [Transference and countertransference at a therapeutic community for young adult psychiatric patients]. AB - Transference and countertransference especially occur in therapeutic communities. Different forms of transference are described here. Experiences and possibilities to deal with are discussed by the example of the work in a therapeutic community. Results of research are considered as well. Finally the course of treatment of an inhabitant with borderline disorders will be recorded with regard to transference and countertransference. PMID- 2309030 TI - [Genetic counseling: values orientation of the counselor and his effect on the decision process of clients]. AB - Counseling sessions, post-counseling questioning and interviews with four counselors of a genetic counseling centre in the Federal Republic of Germany were investigated to work out the counselor's intended and real influence taking upon the counselee's decision making, the reflections of these counselors about the influence, they possibly take, and the values, the counselor's "manner of advising" is based on. PMID- 2309031 TI - [The field of tension between "psychotherapy" and "psychoanalytic therapy" exemplified by West Berlin]. PMID- 2309032 TI - [Typical combinations of personal satisfaction and their relation to symptoms, diagnosis and indications for therapy. I: Various areas of personal satisfaction and their typical combinations]. AB - An empirical investigation (questionnaire) of satisfaction with the professional, financial and sexual situation, relationships and life in general of psychotherapy out patients (n = 562) showed high dissatisfaction with all areas. Life satisfaction showed to be the lowest, financial satisfaction was comparably high. Two main types were found by statistical analysis: one showed satisfaction in all areas, the other one showed dissatisfaction in all areas, both types covering approximately 40% of the sample. The other three types and the antitypes are of lower importance. Satisfaction with relations is a necessary, but not sufficient condition for life satisfaction, professional and sexual satisfaction is also of albeit lower importance. PMID- 2309033 TI - Orthopedics. PMID- 2309034 TI - Pharmacokinetics and adverse effects of single doses of dothiepin in young and elderly subjects. AB - 1. The pharmacokinetics and side-effects of Dothiepin (DOT) were studied for four days after administration of a single oral dose of 75 mg to young adult and elderly subjects. 2. In the elderly DOT is absorbed, distributed and eliminated with half-lives about the same as in young adults but it is cleared less efficiently. 3. This difference of clearance in the elderly, after single-dose administration, is not reflected in increased incidence of side-effects. PMID- 2309036 TI - Effects of haloperidol on recall and information processing in verbal and spatial learning. AB - 1. Normal male subjects were tested with either a multi-trial word list learning test or a spatial analogue prior to administration of either 4 mg. or 10 mg. of oral haloperidol. Six hours after drug administration subjects who had previously received the verbal test were administered the spatial test, and vice versa, so for each test there was a no-drug control group, a group tested after receiving 4 mg. of haloperidol, and a group tested after a 10 mg. dose. 2. Both the verbal and spatial learning tests yield multidimensional measures of components of memory and learning, including measures sensitive to effort-demanding and more automatic information processing operations. 3. Results showed no differences for either test among the pre-drug control group and the 4 mg. and 10 mg. groups, with only one minor exception. 4. The lack of significant results cannot be attributed to insensitivity of the test instruments used, since previous studies have documented sensitivity to a number of clinical conditions and to aging. 5. Results have implications regarding clinical effects of haloperidol. A theory that links dopaminergic functioning with effortful information processing underlying memory and learning was not supported. PMID- 2309035 TI - A pilot study of magnesium aspartate hydrochloride (Magnesiocard) as a mood stabilizer for rapid cycling bipolar affective disorder patients. AB - 1. Nine severe rapid cycling manic-depressive patients were treated with a magnesium preparation, Magnesiocard 40 mEq/day in an open label study for a period up to 32 weeks. 2. Magnesiocard was found to have clinical results at least equivalent to those of lithium in about 50% of these patients. These results were obtained in an exploratory study and should be interpreted with caution. 3. The possibility that Magnesiocard could replace or improve the efficacy of lithium as a preventive treatment of manic-depressive illness merits further clinical investigation. PMID- 2309037 TI - Seasonal stability of water balance among schizophrenic patients subject to water intoxication. AB - 1. Diurnal weight gain, afternoon hyponatremia, and polyuria were assessed for one year among eight male schizophrenics subject to water intoxication. 2. The authors normalized the diurnal weight gain (NDWG) as a percentage by subtracting the 7 a.m. weight from the 4 p.m. Weight, multiplying the difference by 100, and then dividing the result by the 7 a.m. weight. 3. NDWG ranged between 2.69 +/- .99 and 3.34 +/- 1.32 percent (F [3, 5] = .885, p = .509) during the four seasons of the year. 4. The seasonal decrease in afternoon serum sodium compared to its morning counterpart ranged between 4.23 +/- 1.96 and 6.14 +/- 2.82 mmol/l (F [3, 5] = 2.212, p = .205). 5. Seasonal polyuria ranged between 8.2 +/- 3.5 and 8.8 +/ 3.2 liters (F [3, 5] = .228, p = .873). 6. Among schizophrenics subject to water intoxication, the seasonal stability in our three parameters of water imbalance suggest they may be used to follow patients with altered water homeostasis over time. This finding has both clinical and research implications. PMID- 2309038 TI - The long-term effects of diazepam, lorazepam, and buspirone on behavioral suppression by a shock signal. AB - 1. Two experiments examined the long-term effects of treatment with buspirone (a nonbenzodiazepine anxiolytic), diazepam, or Lorazepam (two pharmacokinetically distinct benzodiazepines) on the capacity of a shock cue to disrupt appetitively conditioned behavior. 2. In Experiment 1, rats were injected with diazepam (5 mg/kg), buspirone (1.5 mg/kg or .75 mg/kg), or saline shortly before each of 12 bar press training sessions. Injections were suspended and three days later the rats received five days of Pavlovian fear conditioning (bars removed) in which a tone signaled shock. The capacity of the tone to disrupt bar pressing was then assessed. 3. Bar pressing of rats previously injected with diazepam was more suppressed by the shock cue than that of rats previously injected with buspirone or saline. The long-term effects of buspirone and saline did not differ. 4. In Experiment 2, Lorazepam had effects different from diazepam during bar press training. Nonetheless, rats previously injected with Lorazepam were also more disrupted by a shock cue than were controls. 5. The results suggest that one long term consequence of treatment with benzodiazepines may be hypersensitivity to behavioral disruption by stimuli that presumably elicit fear or anxiety. PMID- 2309039 TI - An EEG and behavioural study on the interactions of clonidine with phencyclidine and ketamine in rats. AB - 1. Clonidine, an alpha-2 adrenergic agonist, induced in rats a synchronization of the electrical activity of the brain (EEG) accompanied by sedation starting from the dose of 0.05 mg/kg, i.p. 2. This drug (0.05 mg/kg, i.p.) was also able to influence both the EEG and behavioural effects elicited by two "dissociative anaesthetics", PCP and KT. 3. At low and moderate doses of these two drugs, clonidine fully inhibited the EEG and behavioural effects, whereas at high doses of both drugs clonidine potentiated these effects. 4. Yohimbine was able to revert the inhibitory and potentiating effects produced by clonidine. It was also able to revert sedation accompanied by EEG synchronization. 5. Prazosin, on the other hand, was not able to produce such effects. This fact suggests that the alpha-2 adrenoceptors are involved in these effects. 6. Based on our findings, the interaction of the dissociative anaesthetics (PCP-KT) with the central adrenergic receptors seems to be very complex. The possible relevance of clonidine on both the improvement of KT-induced anaesthesia and the treatment of PCP-intoxication is also discussed. PMID- 2309040 TI - [Molecular assembly of proteins for creating higher functions--a strategy and tactics for developing next-generation materials]. PMID- 2309041 TI - Concentrations of 13, 14-dihydro-15-keto prostaglandin F2 alpha after pulsatile progesterone administration at the time of luteolysis of heifers. AB - Progesterone was administered in pulses to 12 dairy heifers from days 17.5 to 22.5 post-estrus in order to determine its ability to modify secretion of PGF2 alpha around the time of luteolysis. Control heifers exhibited pulses of PGFM concomitant with a sharp decline in progesterone concentrations and thus these pulses were temporally associated with luteolysis. Additional pulses of PGFM were observed in heifers receiving exogenous progesterone, but these were not statistically predictable by either dose of progesterone (50 or 100 micrograms) or time of administration (3 or 6 hour intervals). However, all heifers (4/4) treated with progesterone at 3 hour intervals had additional pulses of PGFM as compared to only one heifer (1/4) treated at 6 hour intervals. When pulses of PGFM were induced by exogenous progesterone there was a substantial lag time between the initiation of progesterone treatment and their occurrence. The limited response to progesterone administration and the lack of synchrony is not consistent with an ability of exogenous progesterone to directly stimulate secretion of PGF2 alpha at the time of luteolysis. PMID- 2309042 TI - Arginine vasotocin-induced prostaglandin synthesis in vitro by the reproductive tract of the viviparous lizard Sceloporus jarrovi. AB - Two experiments were performed to determine whether arginine vasotocin (AVT) stimulates synthesis of prostaglandins (PGs) in reptilian oviducts. Homogenized oviducal tissue from female Sceloporus jarrovi in early and late pregnancy were cultured with radiolabeled (14C) prostaglandin precursor, arachidonic acid (AA). In late pregnancy, oviducts exposed to AVT exhibited a greater conversion of AA to PGF2 alpha than did controls, whereas in early pregnancy there was no difference. The conversion of AA to other prostaglandins (PGA2, PGD2, PGE2, PGI2) was not influenced by AVT. The second experiment examined whether endogenous in vitro synthesis of PGF and PGE2 from intact, pregnant oviducts was stimulated by AVT (50 ng/ml; 100 ng/ml). Both doses of AVT induced a similar, significant rise in PGF concentrations within 30 min whereas no significant increase was noted in PGE2 concentrations until 90 min after treatment. Indomethacin pretreatment blocked synthesis of both PGF and PGE2 for 30 min following AVT treatment. These data indicate that AVT induces a highly specific rise in the synthesis of PGF from the oviduct of female S. jarrovi in late pregnancy. Furthermore, the prostaglandin-stimulating effect of AVT in reptiles appears homologous with the effect of oxytocin in mammals and AVT in birds. We hypothesize that this interaction is an evolutionarily conserved relationship found in all amniote vertebrates. PMID- 2309043 TI - Prostaglandin E2 and thromboxane B2 levels in rats subjected to pancreas transplantation. AB - This work undertakes the study of changes in urinary, plasmatic and tissue levels of Thromboxane B2 (TXB2) as well as in tissue Prostaglandin E2 (PGE2) after pancreas transplantation and the effect of superoxide dismutase (SOD) on these changes. For this purpose, streptozotocine induced diabetic rats were subjected to pancreas transplantation. Experimental groups were classified as follows: Group I: Control; Group II: Animals subjected to 15 min of pancreas arterial flow occlusion followed by reperfusion; Group III: Syngenic pancreas transplantation after 12 hours of organ preservation; Group IV: Same as III, but with additional SOD (13 mg/kg) pretreatment. The results indicate that significant increases of PGE2 and TXB2 levels occur as a consequence of the surgical removal, preservation and implantation of the organ. For TXB2 these increases, immediate in plasma and tissue, are not detected in urine until 24 hours after transplantation of the pancreas. The release of TXB2 and PGE2 was effectively prevented in the SOD treated group supporting the role of oxygen free radicals and lipid peroxidation in the processes of ischemia-reperfusion associated to transplantation of the pancreas. PMID- 2309044 TI - Intratesticular injection of [D-Met2-Pro5]enkephalinamide suppresses testosterone secretion of the testis of immature rat. AB - The possible role of enkephalin in the local control of testicular function was studied in neonatal rats. 5- and 10-day old hemicastrated rats were treated intratesticularly with an enkephalin analog [D-Met2-Pro5]enkephalinamide. In 5 day-old rats local injection of different doses (0.1-0.3 micrograms/testis) of the peptide suppressed basal testosterone secretion in vitro in a dose-dependent manner 2 h posttreatment. Intratesticular administration of naloxone prior to enkephalin treatment prevented the decrease in basal testosterone production induced by the opioid agonist. In 10-day-old animals intratesticular injection of 1.0 and 3.0 micrograms/testis of enkephalinamide reduced serum testosterone concentration and basal testosterone secretion in vitro. Systemic injection of the peptide produced no change in steroidogenesis. These results suggest that enkephalins might be among the intratesticular factors regulating Leydig cell functions. PMID- 2309045 TI - Effects of pancreatic polypeptide on biliary flow and bile acid secretion stimulated by secretin and cholecystokinin in the conscious pig. AB - Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with biliary and duodenal fistulae for biliary secretion studies. Furthermore, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Bile was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8 day recovery period, infusion studies were performed after an overnight fast. After a 30 min basal period, sustained biliary flow and bile acid output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin plus CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Biliary flow was not affected by PP except for the dose of 400 pmol/kg/h. On the contrary, bile acid concentration and output decreased with the lowest dose of PP (200 pmol/kg/h). As soon as the first dose of PP was infused, bile acid concentration and output fell to about 60% of values obtained with secretin plus CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Bile acid concentration and output did not return to values obtained with secretin plus CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases bile acid output whereas biliary flow remains unaffected. PMID- 2309046 TI - Cholecystokinin binding and degradation by isolated rat liver cells. AB - The present studies were directed to examine and quantify binding and degradation of radiolabelled cholecystokinin (CCK) peptides by isolated rat liver cells. After incubation with liver cells (4.5 x 10(6) cells/ml) at 14 degrees C, minimal binding (less than 5%) of labelled CCK33 was detected. When labelled nonsulfated (nsCCK8) and sulfated CCK8 (sCCK8) were incubated, 16.2 +/- 1.8% (mean +/- S.E.) and 7.2 +/- 0.1% of 125I-nsCCK8 and 125I-sCCK8, respectively, were bound to the cell fraction. However, no inhibition of binding of either labelled nsCCK8 or sCCK8 was observed when incubated in the presence of excess unlabelled peptide (10 ng-10 micrograms). Preferential binding of labelled sCCK8, the biologically active form of the octapeptide, appeared to be to the nonparenchymal liver cell, rather than the hepatocyte, fraction; when corrected for cell size and protein content, binding of sCCK8 was approximately 15-times greater by the nonparenchymal cell population. When incubated with hepatocytes at 37 degrees C for 60 min, no degradation of labelled sCCK8 was detected by high pressure liquid chromatography. In contrast, progressive degradation of sCCK8 was observed when the peptide was incubated with the nonparenchymal cells. The results of these studies confirm previous observations that CCK33 is not bound by the liver. They further demonstrate that to some degree CCK8 is preferentially bound and degraded by hepatic nonparenchymal cells; however, this binding appears to be noncompetitive and, therefore, probably not receptor-mediated. PMID- 2309047 TI - Differential rates of glucose metabolism across subregions of the subfornical organ in Brattleboro rats. AB - We applied [14C]deoxyglucose autoradiography and imaging techniques to determine rates of glucose metabolism in distinct subdivisions of the subfornical organ (SFO) of conscious Brattleboro rats. Seven anatomically-defineD SFO subregions were discerned having metabolic activities that differed from one another by as much as 29% in water-sated Brattleboro rats. The highest metabolic activity was found in the ventromedial zone of central and caudal subregions where previous studies identified the greatest densities of neurons, capillaries, putative angiotensin receptors, and angiotensin-immunoreactive fibers. Homozygous Brattleboro rats had rates of glucose metabolism that were 39-68% greater than those in corresponding SFO subregions of Long-Evans rats; these differences were accentuated by about 50% following 18 h of water deprivation. Exogenous treatment of Brattleboro rats with vasopressin uniformly normalized subregional glucose metabolism in the SFO. In Sprague-Dawley rats, water deprivation over 120 h provoked greater increases in metabolism of ventromedial than of dorsolateral SFO zones in amounts similar to the differences between Long-Evans and Brattleboro rats. The findings identify focal areas of high metabolic activity within subregions of the SFO where central responses are likely initiated to defend against homeostatic disturbances. The data represent further evidence for the probability that angiotensin II, as both hormone and neurotransmitter, is a metabolic stimulant of its target cells in the nervous system. PMID- 2309048 TI - Fibroblast mitogens in swine milk include an epidermal growth factor-related peptide. AB - Mammary secretions obtained from lactating sows can support in vitro growth of mammalian cells when added to Dulbecco's Modified Eagle Medium. In order to identify the growth factors present within, sow milk was fractionated and fractions having mitogenic activity were identified by their ability to stimulate DNA synthesis in density-arrested, quiescent (murine) AKR-2B fibroblasts. A prominent mitogenic activity (peak III) was observed in the 3,000-5,000 Mr range. This activity was partially purified by (1) preparative Sephadex G-200 chromatography, (2) gel-filtration in Sephadex G-50 columns and (3) DEAE cellulose anion exchange chromatography. The last step resolved peak III activity into at least two distinct components. One component was highly-purified by use of reverse-phase high-performance liquid chromatography (RP-HPLC). This activity was identified as an epidermal growth factor (EGF)-related peptide based on its inactivation by polyclonal antibody (IgG fraction) specific for murine EGF (mEGF) and proteolytic agents. The other component is unrelated to EGF. Using cloned mEGF cDNA as a probe, the presence of EGF-related mRNA in lactating mammary tissues and newborn pig small intestine was also demonstrated. These factors may contribute to the preferential growth of gastrointestinal tissues in neonatal pigs. PMID- 2309049 TI - Chemical structure of phospholipids in the lungs and airways of sheep. AB - Experiments on phospholipids from the alveolar lining, bronchi and trachea were conducted to support the concept that different lipid complexes are synthesized and released at different sites in the pulmonary system. Tracheal, bronchial and bronchioalveolar lavages were obtained from healthy adult Merino breed ewes following euthanasia and a structural analysis of the phospholipid fraction made by fast atom bombardment mass spectrometry. The major components in tracheal lavage were: 72% phosphatidylcholines (PC), 8% phosphatidylethanolamines (PE) and 11% phosphatidylglycerols (PG) compared to 78% PC, 13% PE and 3% PG in bronchioalveolar lavage. The fatty acid profile of tracheal lavage showed that 73% of the PG and 3% of the PC contained an arachidonic acid side chain. These species were not found in bronchioalveolar lavage. The nearly four-fold increase in PG, and the different molecular species identified in tracheal compared to bronchioalveolar lavage, suggest local synthesis and release of phospholipids by tracheal epithelial cells. The distribution of these phospholipids may have functional properties desirable for normal mucociliary function and are consistent with published measurements from cultured tracheal epithelia cells. PMID- 2309050 TI - The role of lung perfusate PO2 in the control of the pulmonary vascular resistance of exteriorized fetal lambs. AB - The isolated perfused lower left lung lobe of the exteriorized fetal lamb was used to define quantitatively the relationship between pulmonary perfusate oxygen tension and pulmonary vascular resistance (PVR) in the fetus at multiple oxygen tensions over the range from 8.3 to 433 mm Hg. This allowed variation of the perfusate PO2 over the range of partial pressures from less than 10 mm Hg to over 400 mm Hg while constant values of PCO2, temperature and perfusate flow were maintained. In all animals, calculated pulmonary vascular resistance varied in an inverse manner with the perfusate PO2. The relationship between PVR and perfusate oxygen tension is described by the equation: PVR = 7.67 - 1.54 (log PO2) R2 = 0.70. While others have shown that a single, large increase in blood oxygen tension will decrease the PVR in fetal lambs, these data present the first quantitative description of the role of oxygen tension in the modulation of fetal pulmonary vascular resistance as determined at multiple perfusate oxygen tensions over a fifty-fold range. PMID- 2309052 TI - Human red cell age, oxygen affinity and oxygen transport. AB - The [2,3-DPG]/[Hb] ratio and the P50 were found to be lower in the 10% denser (old) than in the 10% lighter (young) red blood cell (RBC) fractions (0.57 +/- 0.13 vs 0.96 +/- 0.13 and 23.02 +/- 0.85 vs 27.47 +/- 1.05 Torr, respectively, mean +/- SD, P less than 0.0005 for both, n = 6). The RBC aging processes appear thus to affect the RBC oxygen affinity. However, the [2,3-DPG] changes do not fully explain the drop of not fully explain the drop of P50 as measured at constant [H+], [CO2] and [HbCO]. It is therefore postulated that an additional factor is involved in the regulation of the oxygen affinity in the ageing RBC. The RBC density in 59 normal individuals matched for age (infants, adult, and aged) and for sex was found to be younger in adult females than in all other groups (P less than 0.0005), including an age-matched group of pregnant women. Correspondingly, the [2,3-DPG]/[Hb] ratio and the P50 are higher in adult females than in adult males (0.92 +/- 0.10 vs 0.82 +/- 0.09, P less than 0.009, and 29.03 +/- 1.07 vs 27.72 +/- 0.82 Torr, P less than 0.002, respectively). These data are evaluated in terms of the efficiency of the oxygen transport calculating the circulatory load required to transport a given amount of oxygen to the tissues. The results indicate that the lower oxygen affinity (due to the younger RBC population) in adult females partially compensates for their lower [Hb]. PMID- 2309051 TI - Water-responsive laryngeal receptors in the dog are not specialized endings. AB - The primary purpose of this study was to ascertain whether laryngeal receptors activated by water are specialized endings or whether they also respond to other stimuli, such as pressure, temperature and laryngeal motion as they occur during the breathing cycle. In 35 anesthetized mongrel dogs, breathing spontaneously through a lower cervical tracheostomy, water and other test solutions at approximately 37 degrees C were injected into the functionally isolated larynx with a small catheter. Of the 130 receptors studied, none of the cold receptors (N = 13) responded to water, whereas approximately 60% of all laryngeal mechanoreceptors (72 of 117) responded with either a short delay, short duration or a long delay, long duration response. In general the former pattern of response was exhibited by nonrespiratory-modulated receptors, whereas the latter was typical of respiratory-modulated receptors. The specific nature of the stimulus (hypotonicity or lack of chloride ion) of the water response was further studied in 53 receptors with isoosmotic solutions of dextrose and sodium gluconate. The long delay, long duration response was dependent on a decreased osmolality, while the short delay, short duration response was dependent on the lack of chloride ion of the test solutions. All water-responsive receptors tested (N = 17) were blocked within 50 sec by topically applied 2% lidocaine and thus presumed to be superficial. However, 10 receptors which did not respond to water were also blocked within 50 sec, suggesting that not all superficial receptors are stimulated by water. Based on these observations, we propose that changes in osmolality or ionic composition of the laryngeal surface liquid could play an important role in modifying reflexes involved in the maintenance of upper airway patency. PMID- 2309053 TI - Series distribution of mucociliary clearance of magnetized iron particles in anesthetized dogs. AB - Clearance of magnetic iron particles placed in the trachea, peripheral airway and alveoli was studied in anesthetized dogs. A retrograde catheter was inserted into a peripheral airway 2 mm in diameter. A thin vinyl tube was inserted into the peripheral airway from the chest wall through the retrograde catheter and 0.05 ml of saline containing 30 mg of iron oxide (Fe3O4) was instilled into either the peripheral airway or the trachea. Further, 30 mg of Fe3O4 solution was instilled with an injection needle into the alveoli. After magnetization from outside the chest wall, remanent magnetic fields (RMF) generated in the trachea, peripheral airway and alveoli were sequentially measured with a flux-gate magnetometer. The decay of RMF immediately after sequential magnetization shows clearance of Fe3O4 particles. Relaxation of RMF just before sequential magnetization is related to random misalignment of the particles. The fastest clearance was observed in the trachea, followed by the peripheral airway and the slowest was that in the alveoli. Exposure to isoproterenol resulted in increased clearance in the trachea and peripheral airway. However, relaxation was of similar magnitude and was not altered by isoproterenol throughout the entire airway. These results suggest that mechanisms responsible for clearance and relaxation in vivo are different and that clearance accelerates toward the central airway from alveoli and relaxation may be due to properties of the airway surface lining layer. PMID- 2309054 TI - Prevention and treatment of ligamentous sports injuries to the hand. AB - Sports-related injuries to the intricate small joints of the hand are quite frequent. The majority of such injuries result in joint contusions, partial tears or ligament sprains which do not jeopardise the basic stability of the joint and readily respond to a short course of protective splinting with rapid recovery of motion, strength and function. In fact, many patients never seek medical attention unless persisting pain, chronic swelling or restriction of motion persuade them to do so. Partial tears or sprains need to be distinguished from more serious injuries that cause profound ligamentous and capsular disruption resulting in dislocations, articular incongruency, joint instability or fracture dislocations. While simple dislocations are readily reducible and generally stable, a complex dislocation by definition implies irreducibility by closed means. This category of complex joint injury requires prompt diagnosis, as optimal management warrants active surgical intervention to achieve a stable and congruous reduction. Following surgical repairs the injured joint is immobilised for a variable length of time, determined by the type, extent and the nature of the specific injury, prior to initiating remobilisation efforts. A supervised and well-executed rehabilitation programme should encompass all the various modalities of physical therapy that are effective in increasing mobility, correcting deformity and restoring strength and function to the injured hand. The ultimate goal of treatment is to enable the athlete to resume sports, unimpaired with the same skill, dexterity and competitive edge as before. PMID- 2309055 TI - [What is your diagnosis? Exertion-induced ventricular tachycardia]. PMID- 2309056 TI - [Callosal disconnection syndrome caused by left hemisphere infarction]. AB - A 49-year old right-handed taxi-driver experienced right upper limb weakness and global aphasia following internal carotid artery occlusion. Five months later, aphasia and hemiparesis had resolved but he complained of difficulties in his daily activities, termed "inner conflict". Specific testings disclosed typical features of a callosal syndrome: left unilateral ideomotor apraxia, left hand agraphia, left tactile dysnomia, right hand constructional difficulties, and left ear extinction on dichotic listening. Naming and recognition of tachistoscopically presented images or words was similar to that of classical split-brain studies. MRI showed a left-hemisphere periventricular increased signal involving the callosal outflow of the whole posterior half of the corpus callosum and partially destroying the splenium. Fibers from the anterior half of the body and the genu were spared. According to clinical and MRI findings in this case and other documented cases of callosal syndrome, localization of callosal transfer of various hemisphere functions is discussed. The relevance of callosal symptoms to the diagnosis of watershed infarcts is emphasized. PMID- 2309057 TI - [Paroxysmal kinesigenic choreoathetosis: autonomic disease or reflex epilepsy?]. AB - Motor attacks induced by voluntary movements are infrequent. Paroxysmal kinesigenic choreoathetosis (PKC) is rare and has only recently been individualized (Kertesz, 1967). We report the case of an 8 year-old boy who developed unilateral or bilateral attacks of abnormal, choreoathetotic movements during certain voluntary movements, especially when rising after a rest. The attacks were short (13 to 18 seconds) and frequent. Neurological examination was normal, as were the intelligence quotient, the inter-critical and critical EEG: CT and MRI. The patient's mother had suffered from the same disorder. The attacks disappeared during treatment with phenytoin but reappeared when it was stopped. This case is concordant with data from the literature, with male predominance, age from 6 to 15 years at the onset, shortness of the attacks (less than 1 minute in 80% of the cases) and normality of investigations in almost every patient. A familial factor has been found in 50% of the cases. The frequency of epilepsy in the family is above average. PKC can easily be distinguished from Mount and Reback' syndrome where the attacks are choreoathetotic but longer and unprovoked by movements and where there is also a familial factor. The relationship of PKC with epilepsy is asserted by some authors and denied by others, and in the literature the distinction between movement-induced tonic seizures and PKC is not always clear. Some authors have blamed a disturbance in the maturation of basal ganglia. To sum up, PKC is a very rare condition which is easy to diagnose, has a good prognosis and readily responds to antiepileptic drugs. PMID- 2309058 TI - [Bilateral paresis of the superior oblique muscle caused by hematoma of the mesencephalic tegmentum]. AB - Primary hematomas of the brain stem are rare. We report the case of a small spontaneous mesencephalic hematoma which occurred in a 50 year-old normotensive male patient. The hematoma produced paresis of the superior oblique muscle and a lesion of the left spinothalamic tract. The outcome was favourable. PMID- 2309059 TI - [A new method of quantitative analysis of parkinsonian gait: report of 6 patients]. AB - A simple quantitative method of gait analysis in parkinsonism is presented. In this method, spatial and temporal parameters (stride length and duration, stance duration and double support duration) and cinematic parameters (velocity) were evaluated. A pilot trial performed in 6 patients highlighted the pathological aspect of the parkinsonian gait as compared to the gait of healthy elderly subjects. A significant degradation (reduced speed, diminished stride length, short duration of the double support stage) was noted, even when parkinsonians were compared with the oldest of the control subjects. PMID- 2309060 TI - [Lobar holoprosencephaly associated with heterotopic gray matter. A case disclosed in adulthood by epilepsy]. AB - A case of lobar holoprosencephaly associated with heterotopias of the grey matter is reported. The patient was a young woman whose cerebral malformation was revealed by epileptic seizures at the age of 22. There was no intellectual deficit. Computerized tomography and, chiefly, magnetic resonance imaging, enabled the study of the malformation. PMID- 2309061 TI - [Communicating hydrocephalus disclosing neurosyphilis]. AB - A case of normal pressure hydrocephalus associated with neurosyphilis is reported. The outcome was favourable after penicillin therapy and subtraction of CSF. PMID- 2309062 TI - [Conference at the Salpetriere. February 1988. Muscular weakness and respiratory distress in a 40-year-old woman]. PMID- 2309063 TI - Recent developments concerning the carcinoembryonic antigen gene family and their clinical implications. Report on the XVIIth meeting of the International Society for Oncodevelopmental Biology and Medicine, Freiburg, FRG (September 18-22, 1989). PMID- 2309064 TI - Characterization of monoclonal antibodies reactive with normal resting, lactating and neoplastic human breast. AB - Mouse monoclonal antibodies reacting with human mammary gland constituents have been generated and characterized in an attempt to raise breast- or breast-cancer specific antisera. The immunogens used in these studies included fractionated human milk fat globule membrane, the human breast cancer cell line MCF7 and a crude membrane preparation derived from an axillary nodal metastasis from a patient with breast cancer. Of the antibodies obtained, 8 were characterized and found to bind to different structures in the normal breast. The antibody LICR-LON LC28 recognizes secretory component and binds strongly to normal resting and lactating breast, but only focally to a minority of breast carcinomas. The antibodies LICR-LON-14.1 and 32.2 react strongly with the lactating breast and recognize kappa- and beta-casein, respectively. Caseins are not produced by breast tumors. The antibodies LICR-LON-TW19.5, H10A and 39.8 all react with carbohydrate epitopes and bind heterogeneously to normal resting breast luminal epithelium and cellular subsets of breast carcinomas. LICR-LON-59.2 and 19.2 react with normal breast myoepithelial cells and the basement membrane, respectively. LICR-LON-59.2 is unusual as a myoepithelial marker in that it stains cells in the majority of breast carcinomas. LICR-LON-19.2 shows extensive reactivity to tumor cell lines in culture but has no reactivity with carcinoma cells from breast biopsies. PMID- 2309065 TI - Serine proteinase inhibitors produced by human melanoma cell lines. AB - The human melanoma cell lines M21 and MSM-M2 are shown to produce two similar competitive inhibitors of trypsin, a serine proteinase. These proteinase inhibitors inhibited the serine proteinases trypsin and kallikrein with similar efficiency but did not inhibit plasmin (a serine proteinase) or papain (a thiol proteinase). Active synthesis of the inhibitors during cell culture was indicated by the requirement for cell viability, the increase in inhibitory activity of the supernatant with time, and the incorporation of 35S-methionine into the inhibitors. The two inhibitors were stable to heat (70 degrees C) and extremes of pH. Their molecular weights were estimated at 670 and 250 kD, respectively. A screening of the supernatants of five other human melanoma cell lines by HPLC showed that they all released a similar trypsin inhibitory factor not detected in human or bovine serum. The isolation of these proteinase inhibitors facilitates a study of their putative role in tumor growth. PMID- 2309067 TI - Workshop report: proposed nomenclature for the carcinoembryonic antigen (CEA) gene family. PMID- 2309066 TI - Mechanism of clearance of circulating CA19-9 in rats. AB - Molecules bearing the carbohydrate antigen 19-9 (CA19-9) epitope were prepared from serum and ascites of a patient with colon cancer or from the SW 1116 cell culture supernatant. Their plasma clearance mechanism was investigated in rats. The clearance curves of the molecules from three different sources showed a biphasic decrease. The coexistence of epitopes of CA19-9 and desialylated CA19-9 (Lea) in the same molecule was demonstrated by double-determinant enzyme immunoassays. CA19-9-bearing molecules with a low expression of Lea epitope, which were derived from the serum of a patient with colon cancer, showed mainly a slow disappearance, while the molecules with a high expression of Lea epitope from SW 1116 cells showed mainly a rapid disappearance. Thus, the clearance rate of the CA19-9-bearing molecules might be determined by their degrees of sialylation. This observation will be helpful for understanding the in vivo metabolism of CA19-9-bearing molecules. PMID- 2309068 TI - Abstracts presented by members of the ISOBM. International Society for Oncodevelopmental Biology and Medicine. XVIIth meeting. Freiburg, September 18 22, 1989. PMID- 2309069 TI - [Menstrual migraine]. AB - The cyclic fall in oestrogen level associated with the beginning of menstruations produces common migraine in 10 to 20 p. 100 of women in the general population. In women who already have migraine, the menstruations coincide with triggering or worsening of the attacks in 60 p. 100 of the cases. About 1 out of 10 women who do not have spontaneous menstrual migraine begin to suffer regularly as soon as they take an oral combination contraceptive. High doses of antigonadrotropic progestogens make the attacks worse because they herald or enhance the hypoestrogenaemia. Insufficient doses of oestrogens administered orally induce brief daily episodes of increased, then decreased oestrogenic stimulation, and they also facilitate the occurrence of migrainous attacks. The best available preventive treatment consists of cyclic percutaneous administration of oestradiol in doses that are sufficient to stabilize blood oestradiol levels at 60-80 pg/ml during the critical week. This treatment is the only one that prevents migrainous attacks and preserves the menstrual cycle. Obviously, it only benefits women with menstrual migraine, and fluctuations in oestradiolaemia are only one of the multiple precipitating factors of migrainous attacks. PMID- 2309070 TI - [Headache of cervical origin]. AB - Neck disorders implicated as causes of headache fall into two groups: a) those in which the cervical lesions are unequivocally demonstrable, and in which treatment of those lesions helps the headache; these are widely accepted as causes of headache, and include: congenital and acquired craniovertebral junction disorders, rheumatoid arthritis and ankylosing spondylitis of the upper cervical spine, and dissection or trauma to the carotid or vertebral arteries; b) those in which the neck disorder is either banal or not objectively demonstrable, and which seldom improve following treatment of the neck; these are not widely accepted as causes of headache; they include whiplash syndrome, segmental hypomobility-hypermobility syndrome, the posterior cervical sympathetic syndrome, cervical migraine, third occipital nerve headache, and cervicogenic headache. Features of a headache suggesting its cervical origin are: 1) abrupt onset following sudden excessive movement of the head; 2) persistent unilateral suboccipital or occipital pain; 3) consistent reproduction by neck movements and by nothing else; 4) abnormal postures of head and neck; 5) significant painful limitation of movement of upper cervical spine; 6) abnormal mobility at craniovertebral junction; 7) C2 sensory abnormalities or lower medulla or upper cervical cord signs. PMID- 2309071 TI - [Tension headache and psychogenic headache]. AB - Psychogenic headache in the French nosology and the Anglo-Saxon concept of tension headache have many points in common but are not quite identical. Tension headache includes headaches in which the psychic element may be associated with muscular, articular or other causes. Subjects with this type of headache feel as though their skull was compressed by a tight helmet and was heavy, or as though the back of their neck and the occipital region were under tension. The condition is chronic and often lasts for long periods. Psychological and psychopathological analysis discloses the genesis of this tension headache which may simply be a response to a more or less repetitive stress or to anxiety and/or depression, but may also be the somatic expression of a neurotic state with a more consistent structure. This analysis leads to a treatment which includes psychotropic drugs, but where the relational component remains fundamental in the management of these patients. PMID- 2309072 TI - [Unusual headaches]. AB - Cluster headache, ice pick headache, cough and effort headaches, and headaches related to sexual activity are unusual forms of headaches which are not treated elsewhere in this Revue du Praticien. They are briefly described. PMID- 2309073 TI - [Headaches after lumbar puncture and their treatment]. AB - The principle mechanism of post lumbar puncture headache is the leakage of CSF from the dural puncture site. This leads to a state of low sub-arachnoid pressure, causing traction on pain-sensitive intracerebral structures. The operator can minimise the risk of headache by selecting a needle of small diameter and ensuring that the bevel is aligned parallel to the longitudinal fibers of the dura. Current evidence suggests that the patient may be allowed to mobilise immediately. Traditional therapies such as bed rest and rehydration are usually ineffective when headache is severe. If this is the case, and the diagnosis is certain, a blood patch procedure can be performed, and repeated if necessary. PMID- 2309074 TI - [Headaches, cranial neuralgias, facial pain, classification and diagnostic criteria. International Headache Society]. PMID- 2309075 TI - [Biocompatibility of membranes: long-term effects]. PMID- 2309076 TI - [5th meeting of the French Pancreas Club. Paris, 28 October 1989]. PMID- 2309077 TI - [Anti-arrhythmia drugs. Drugs one must know to prescribe]. PMID- 2309078 TI - [Loss of consciousness, convulsive seizure. Diagnostic orientation and procedures to follow]. PMID- 2309079 TI - [Acute respiratory failure. Principles of emergency treatment]. PMID- 2309080 TI - [Suicide. Risk factors and prevention]. PMID- 2309081 TI - [Arthrography of the temporomandibular joint]. AB - In 1989, opaque contrast arthrography of temporomandibular joint is still seldom used. A brief historical review of the procedure is presented here, and the technique of puncturing the menisco-condylar and menisco-temporal compartments is discussed. The value of injecting opaque contrast material into the lower compartment and carrying out kinetic and tomographic studies as well as bilateral examinations is stressed. Normal aspects are described with their variants, as well as pathological ones (reducible and non-reducible luxations, perforations, distension of the bilaminar zone, adhesions, etc.). Both the place of arthrography in relation to other investigations (TDM, IRM) and its indications for visualization of menisco-condylar problems are discussed. PMID- 2309082 TI - The indications of arthroscopic sweep for the patient with internal derangements of the temporomandibular joint (T.M.J.). AB - The arthroscopy of the temporomandibular joint (TMJ) is recently recognized as the useful diagnostic manner as well as the alternative surgical procedures in the treatment of TMJ internal derangements. Arthroscopic surgery of the TMJ, which consists of arthroscopic sweep with lysis of adhesion and lavage of the upper joint compartment, is simple and less surgical invasive manner for the patient with closed lock. The instrumentation, procedure, patient management, and clinical evaluation are described. PMID- 2309083 TI - Diagnostic approach in temporal mandibular joint (T.M.J.) internal derangements using CT-scan. AB - The use of CT-scan diagnostic method in cases with internal derangements of TMJ is discussed. The applied technique, the findings in our series of patients and the advantages and disadvantages are described. The axial tomography seems to be of a high-interest diagnostic method and very useful for the majority of patients. PMID- 2309084 TI - Magnetic resonance imaging of the temporomandibular joint (TMJ) meniscus. AB - By means of surface coils, magnetic resonance makes it possible to achieve high resolution images of the temporomandibular joints. An outstanding tissue contrast with direct imaging of the Discus articularis and changes in its placement can be obtained by choosing adequate sequences. PMID- 2309085 TI - [Contribution of air computerized tomography of the joint in the assessment of algo-dysfunctional syndromes of the mastication system]. AB - The prospective study of evaluation temporomandibular dysfunction by air computerized tomography of the joint are reported. The authors propose a new injection technique of both articular compartments by CT Scan location. With thin sagittal computed tomography sections, closed mouth and open mouth position, this study is made. Preliminary data from air computerized tomography of the joint imaging show directly the disk with anterior and posterior attachments. The authors present the normal results and major pathology found in the evaluationof temporomandibular dysfunction. CT Scan puncture is more precise. The air computerized tomography imaging of the joint was undoubtedly superior to that of conventional opaque joint tomography, but dynamic notion is much less than in the absence of videoscopy. PMID- 2309086 TI - [Comparative study of the temporomandibular joint using conventional radiology and radioisotope scanning]. PMID- 2309087 TI - [Trans-zygomatic approach to the temporomandibular joint]. AB - The articular eminence of the temporal bone may be removed and resect without modifying substantially joint function. Such temporal resection allows for complete exploration and renders surgical treatments easier. The technique which is described here has been carried out on over one hundred patients with a follow up period spanning 5 years or less. Indications are specified and the approach of interest seems to be complementary to the conventional lateral approach of the temporomandibular joint. PMID- 2309088 TI - Arthroscopy and arthroscopic surgery of the temporomandibular joint (T.M.J.). AB - Arthroscopy consist of the insertion of a rigid endoscope into a joint compartment for observation and therapeutic purposes. Since the joint space of TMJ is small, the Indications for arthroscopy in the TMJ were very limited, but with the development of a needle type rigid arthroscope in 1974 in Japan, we began applying this instrument clinically. When arthroscopy is performed, decisions should naturally be made with careful consideration given to the indications. The reason for this is that, in cases where arthroscopy is performed for the purpose of diagnosis, the invasion required for arthroscope perforation might cause more damage than the lesion in the joint. In such cases, consideration must also be given to the after-effects of the damage resulting from the arthroscopy. Therefore, preoperative tests for arthroscopy should be carefully performed and thorough consideration should be given to the indications for arthroscopy based on an understanding of the degree of the lesion in the joint. The indications for arthroscopy should again be carefully considered in cases where diagnosis is made by arthroscopy but it is assumed that the lesion cannot be treated. We first perform arthroscopy on cases considered to be indicated for operations under arthroscopy from preoperative diagnosis, and then perform the operation under arthroscopy once the lesion has been confirmed. Care must be taken that the joint is not damaged uselessly when arthroscopic diagnosis is performed without treatment. Before performing arthroscopy of the TMJ it is extremely important to perform arthrography, especially double contrast arthrotomography and contrast CT, in order to evaluate the condition of the joint space.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309089 TI - [The place of mandibular condylectomy in surgery of temporomandibular joint dysfunction]. AB - Mandibular condylectomy is one of the methods to which one must sometimes resort when treating temporomandibular joint dysfunction. As emphasized by Merville, this is the conventional method used whenever dealing with condylar hypertrophy , as well as in certain grade-III cases with deep bite. However, another interesting indication for it is the horizontal configuration of the occlusal plane, leading to pain and/or luxation. This type of surgical joint operation presents no risk whatsoever, provided the meniscus is respected. PMID- 2309090 TI - Surgery on temporomandibular joint (T.M.J.) in cases with internal derangements. AB - In this work the surgical intervention in cases with internal derangements in T.M.J. is discussed. The cases where the surgery is applied, the surgical technique and the results taken out of our own patients are referred. The final conclusion is that the surgery gives good results only in well and carefully selected cases. PMID- 2309091 TI - Possibilities of conservative treatment of some temporomandibular joint (T.M.J.) diseases on the basis of our clinical material. AB - The aim of this paper is to present our experience in the conservative treatment of T.M.J. diseases during the past 13 years. PMID- 2309092 TI - [Reconstruction of the temporomandibular joint and its alternatives]. AB - Reconstruction of the temporomandibular joint is always quite problematic. --Use of a prosthesis. Many prostheses have been propounded to deal with the operational problems. As, in our opinion, these seem not to meet the usual orthopaedic surgery requirements, we developed a totally intermediate prosthesis with non-sealed cupula. The use of this prosthesis, whenever feasible, provides the solution for the problems with which we have to contend during reconstruction surgery in traumatology and degenerative or tumoral disease. Nonetheless, its use remains limited to adults. --Utilization of biological material: following numerous attempts made with the conventional osteocartilagenous grafts (metatarsal, rib), we believe that the proper orientation, walking in Chang's footsteps, is toward the use of the head of the second metatarsal bone as a microanastomotic transfer. It seems to us that this technique must be used in children, particularly those with malformation syndromes or ankylosis. PMID- 2309093 TI - Development and clinical application of the total temporomandibular joint (T.M.J.) endoprosthesis. AB - In the course of designing a T.M.J. endoprosthesis we performed biomechanical analysis for testing the stress relationships of the condyle. The photoelastic stress analysis showed that the compressive force in the glenoid fossa varied from 90 to 270 N. The experiments showed also that the selected shape of the prosthetic condyle absorbs the forces of the mandible in a way similar to the natural condylar process. Therefore, we developed a total T.M.J. endoprosthesis. The condyle is made of a Titanium--alloy, the socket of high density polyethylene. From 1978 to 1987 we implanted 25 endoprostheses in 18 patients. The mean age of the patients at the time of the operations was 33 years. Indications for the implantation of total T.M.J. endoprostheses in adults are ankylosis, tumours, multiple fractures and, after all possibilities of conservative treatment have been exhausted, severe deforming arthropathy. PMID- 2309094 TI - [Prosthetic rehabilitation in temporomandibular joint dysfunction based on electromyographic and radiological findings]. AB - The authors present four clinical cases for which they used the same diagnostic approach as for the study of craniomandibular disturbances. The clinical examination provides a diagnostic clue and, consequently, orients toward the proper selection of paraclinical tests for neuromuscular and radiological investigations. After some time, prosthetic rehabilitation will also be controlled by the same means. PMID- 2309095 TI - [Symposium on the temporomandibular joint. Toulouse, 28-30 September 1988. Proceedings]. PMID- 2309096 TI - [Tomographic aspects of the temporomandibular joint (TMJ). Comparative study of 30 subjects with rheumatoid arthritis and 30 normal subjects]. AB - From a prospective study, two populations are compared: 30 Healthy subjects with 30 subjects suffering from rheumatoid arthritis. Two conclusions are statistically significant: --The temporo-mandibular joint is affected like the other joints in the rheumatoid arthritis, --the lesions are often bilateral. Two radiographic aspects, are most often observed: the erosion and the lacuna. PMID- 2309097 TI - [The value of mandibular kinesiography and of T-scanning in the diagnosis and treatment of algo-dysfunctional syndrome of the temporomandibular joint]. AB - The application of T-Scan and kinesiographic techniques in combination with electromyography is of great value to the clinician for substantiating certain clinically hard-to-evidence factors, such as chronology and strength of contact points, muscular activity, or certain mandibular movements. The utilisation of these methods is of benefit for diagnosis, treatment and objective patient follow up. PMID- 2309098 TI - [Condylar retrusion in the algo-dysfunctional syndrome of the mastication apparatus]. AB - Although T.M.J. dysfunction-pain syndrome is a multicausal affection, it is obvious that occlusal disturbance is one of the greater etiologic factors. In order to evaluate the role of condylar position in the glenoid fossa, a statistical study has been made on a 16 patients series. These patients presented an uni- or bilateral T.M.J. dysfunction-pain syndrome without arthrosis, ankylosis or traumatologic deformation. The vertical and horizontal relationships of the mandibular condyle to the temporal were quantitatively evaluated from lateral tomographs. Pain and clicking were noted (Y or N) for each of the 32 T.M.J. Condylar position doesn't seem to have any relation with clicking, which is present in cases of meniscus anterior displacement. On the contrary, condylar horizontal retrusion is statistically connected with pain (p less than 0.05) even if one can see condylar retroposition without pain. On the other hand, vertical changes in condylar position cannot be connected with pain. The importance of condylar retrusion in the pain-group can surely be related to inflammatory histologic injuries at the level of the posterior disc attachment. Then, in these cases, the etiologic treatment must be focused on anterior mandibular release by orthodontics, prosthetics or orthognathic surgery. PMID- 2309099 TI - apo-SAA1/apo-SAA2 isotype ratios during casein- and amyloid-enhancing-factor induced secondary amyloidosis in A/J and C57BL/6J mice mice. AB - A/J mice are resistant while C57BL/6J are susceptible to casein-induced secondary amyloidosis. One mechanism responsible for this phenotypic expression of resistance/susceptibility was shown to operate at the level of production of the 'amyloid-enhancing factor' (AEF). AEF and processing of the apo-SAA protein appear almost concomitantly during amyloidogenesis. In order to determine if AEF played a role in the processing of the apo-SAA protein, three major parameters (apo-SAA1/apo-SAA2 ratios, level of AEF, and fibril formation) were determined during casein-induced secondary amyloidosis. Kinetics of AEF production and serum levels of the two major apo-SAA isotypes were compared in A/J and C57BL/6J animals. Both strains showed equal relative amounts of the two isotypes after seven, 15 and 21 casein injections, irrespective of the fact that the A/J strain had no detectable level of AEF and no amyloid deposition; while C57BL/6J mice had a high AEF level and were amyloidotic after 15 and 21 injections. An increased apo-SAA1/apo-SAA2 ratio due to a decrease in apo-SAA2 was noted after 38 days of casein injections when both strains had extensive deposits of amyloid fibrils. Involvement of AEF as an effector molecule was determined by following the ratio of the two major serum apo-SAA isotypes and fibril formation during an accelerated protocol of amyloid induction in C57BL/6J animals. AEF had no direct effect on apo-SAA isotype ratios in the serum. PMID- 2309100 TI - Effects of heat shock on cytolysis mediated by NK cells, LAK cells, activated monocytes and TNFs alpha and beta. AB - We have recently shown that a heat treatment of a murine target cell line, WEHI 164, induces resistance to lysis mediated by tumour necrosis factors alpha (TNF alpha) and beta (TNF-beta). In the present study the effect of the heat shock of target cells on cytotoxicity mediated by natural killer cells (NK cells), lymphocyte-activated killer cells (LAK cells), activated monocytes, TNF-alpha, and TNF-beta was investigated. First, WEHI 164 cell line and six human cell lines (ME 180, K 562, U 937, HeLa, MCF7, and SK-OV 3) were screened for their sensitivity to different forms of lysis, and then sensitive cell lines were heat treated. Pretreatment of target cells at 42 degrees C for 45-60 min also rendered human target cell lines more resistant to lysis by rTNFs, and the acquired resistance was accompanied by an increased resistance to activated monocytes, but not to NK cells or LAK cells. Thus, the heat-induced resistance mechanisms capable of protecting target cells from lysis by rTNFs and by activated monocytes do not elicit resistance to lysis by NK cells and LAK cells, supporting the hypothesis that mediators other than TNFs are involved in NK cell- and LAK cell mediated killing. PMID- 2309101 TI - Differential activation of monocytes in haemodialysis patients exposed to different types of membranes. AB - Peripheral blood mononuclear cells (PBMC) from haemodialysis patients treated with different types of membranes were isolated, incubated in vitro, and extracellular and cell-associated interleukin I (IL-1) assayed by radioimmunological methods. Extracellular IL-1 was low and not different from controls, regardless of the dialyser used. In contrast, cell-associated IL-1 was increased in patients treated with dialysers containing low-flux Cuprophan (CU, n = 5) and polyacrylonitrile sheet membrane (AN69, n = 5). Patients treated with dialysers containing high-flux polysulphone (PS, n = 7), and polymethylmethacrylate (PMMA, n = 8), exhibited no increase in cell-associated IL 1 under these conditions. To elucidate the mechanism of the activation, aqueous extracts of dialysers containing CU, PS, and AN69 were tested for their ability to induce IL-1 generation in PBMC from healthy donors. Extracts from unrinsed CU containing dialysers caused significant IL-1 synthesis and release, whereas incubation with extracts from dialysers containing PS and AN69 sheet membranes did not. Hence, although both CU and AN69 sheet-type dialysers result in activation of blood monocytes the mechanism of action appears to be different. We speculate that functional signs of PBMC activation as evidenced by increased spontaneous IL-1 production observed in some patients on long-term haemodialysis may result from extractable dialyser membrane material while in other instances direct cell membrane interactions or endotoxin transfer from the dialysate may be relevant. PMID- 2309102 TI - Dynamic versus static training in patients with rheumatoid arthritis. AB - Sixty-seven patients with classical or definite rheumatoid arthritis (RA) were studied concerning the effects of standardized physical training on muscle function in the lower extremities. The patients were randomly assigned to four different training groups and were given 6 weeks of training supervised by a physiotherapist at a health care centre. The groups differed according to type (dynamic or static) and extent (12 or 4 times) of training. During this training period as well as for an additional 3 months, the patients carried out programs of exercise at home (either dynamic or static). A significantly greater increase in function during the 6-week period as regards muscle strength, endurance, aerobic capacity, and functional ability was found for the dynamic as compared with the static groups. The findings at follow-up 3 months later were similar. The effectiveness of the programs did not vary with the extent of training. In conclusion, in RA patients, dynamic training gives a greater increase in physical capacity than does static training. PMID- 2309103 TI - A retrospective clinical and neuroimmunohistochemical study of rheumatoid arthritic patients with atlanto-axial subluxation. AB - In a retrospective study of 87 RA patients with radiographically documented anterior atlanto-axial subluxation (AAS) in flexion-extension radiographs, 40 had been studied radiographically before they developed AAS. Of these 40 patients, 34 had had occipitocervical pain already before the subluxation. This shows that pain early in the course of the rheumatoid cervical spine is not caused by or associated with AAS itself. In a separate operatively treated group of 5 patients, ligament neuroanatomy in AAS was more closely studied, using specific heteroantisera to cytoskeletal neurofilaments and various transmitter neuropeptides as neural markers and the highly sensitive avidin-biotin-peroxidase complex (ABC) immunohistochemical staining procedure. These specimens were obtained from the ligamentous structures between the posterior arch of the atlas and the spinous process of C2, corresponding to the C1-C2 interspinal non inflammatory ligament, during atlanto-axial stabilizing operations. This ligamentous tissue contained, in addition to focal inflammatory cell infiltrates, neurofilament and/or neuropeptide immunoreactive neural elements. This finding may suggest that pain early in anterior AAS could be caused not only by synovitis, for example, but also by local ligamentary involvement leading to irritation of local neural elements. This phenomenon may have contributed to the local occipitocervical pain experienced by 34/40 patients who later developed AAS. PMID- 2309104 TI - Sjogren's syndrome in systemic sclerosis. A clinical study of 26 patients. AB - Features of Sjogren's syndrome were sought in 26 patients with systemic sclerosis and in age- and sex-matched control subjects. The assessments included a structured history to establish symptoms of dry eyes and dry mouth. Schirmer's I and II tear tests. Rose Bengal staining with slit lamp microscopy of the eyes, measurement of basal and stimulatory salivary secretion. We measured sweat secretion rates from the skin. Salivary scintigraphy and skin biopsies were performed on the patients. Only one patient showed the complete picture of Sjogren's syndrome with both clinical and investigational evidence of lacrimal and salivary gland involvement. A further patient had an abnormal Schirmer's II test and xerostomia with reduced salivary secretion and an abnormal scan, but no ocular symptoms and no keratoconjunctivitis sicca on ophthalmological examination. Two patients had reduced salivary flow and a dry mouth. A number of patients and control subjects showed various individual symptoms and signs of lacrimal and salivary disorders. These features alone are not sufficient for the diagnosis of Sjogren's syndrome. There is a clear need to adopt strict criteria for diagnosing the condition. The association of Sjogren's syndrome with systemic sclerosis seems doubtful and if it does occur it is very much less common than previously suggested. PMID- 2309105 TI - Reduced strength of skin in Ehlers Danlos syndrome, type III. AB - The biochemical properties, ratio collagen type I/type III and the pattern of reducible collagen crosslinks were studied in skin biopsy samples from 10 patients with Ehlers Danlos syndrome type III (ED III) and 10 age- and sex matched controls. The ED III patients had marked reductions in skin strength and stiffness (42% and 22%, respectively). The ultimate extensibility of the skin, however, was not different from that of the controls. Consequently, a certain load applied to the skin of these patients results in greater deformation than in that of the controls, due to reduced stiffness. The bursting limit is no different from that of the controls. Thus the skin in the ED III patients is not hyperextensible, it merely has reduced strength and stiffness. The reduction in strength could not be explained by differences in skin thickness or collagen content. Skin thickness, collagen content and ratio collagen type I/type III were the same as in the controls, as also was the pattern of reducible collagen crosslinks. These alterations in the mechanical properties of the skin of patients with ED III may be attributable to the molecular structure of the mature collagen or the arrangement of the collagen fibres. PMID- 2309106 TI - Lyme borreliosis among Danish patients with arthritis. PMID- 2309107 TI - Influence of specific anti-salmon calcitonin antibodies on biological effectiveness of nasal salmon calcitonin in Paget's disease of bone. PMID- 2309108 TI - Scleroderma after therapy with appetite suppressants. Report on four cases. PMID- 2309109 TI - High-dose immunoglobulin therapy in pericarditis caused by SLE. PMID- 2309110 TI - [The treatment of anemia of hemodialysis patients using recombinant human erythropoietin: comparison between intravenous and subcutaneous administration]. AB - Recombinant human erythropoietin (r-huEPO) is now an established therapy for anemia of hemodialysis patients. However, questions remain concerning the optimal maintenance dose as well as the route and frequency of administration. This prospective study was designed to determine whether subcutaneous r-huEPO at a reduced dosage was as effective as intravenous r-huEPO in maintaining constant hemoglobin levels. It involved 12 patients on hemodialysis, previously treated with intravenous r-huEPO for 11.8 +/- 7 months (mean +/- SD). For 3 months hemoglobin was kept at a stable level of 10-13 g/dl with individually titrated intravenous r-huEPO administered thrice weekly after each hemodialysis. Patients were then switched to subcutaneous r-huEPO. Initially, approximately 50% of the previous weekly dose was given as twice weekly subcutaneous injections. During the following 3 months the r-huEPO dosage was adapted to maintain the target hemoglobin level. 3 patients did not complete the second period due to acute intercurrent complications not related to therapy. 9/12 patients completed the study. The hemoglobin concentration was kept at a constant level of (mean +/- SD) 10.5 +/- 1.1, 10.6 +/- 0.9 and 11.1 +/- 0.6 g/dl with 233 +/- 110, 246 +/- 118 and 233 +/- 116 U/kg/week of intravenous r-huEPO for the first 3 months. In the second period hemoglobin was kept at 11.5 +/- 1.2, 11.3 +/- 1.4 and 11.1 +/- 0.9 g/dl with 119 +/- 61, 118 +/- 60 and 137 +/- 78 U/kg/week of subcutaneous r huEPO. 2 patients required an increase in the r-huEPO dose during the third month of the second period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309111 TI - [Acute hepatitis following administration of fansidar]. AB - Since 1971 pyrimethamine-sulfadoxine (Fansidar, Roche) has been used worldwide for prophylaxis and therapy of chloroquine resistant Plasmodium falciparum malaria. The drug monitoring team of the producing firm has received reports of a number of cutaneous adverse reactions, some severe, and a few even with fatal outcome. Liver reactions were also encountered, with severe cases only in the recent literature. We report on two patients with hepatitis in temporal relationship to pyrimethamine-sulfadoxine, the first with a second event after later exposure to the same drug. After discontinuing the medication the liver function abnormalities returned to normal limits within a few weeks. Liver biopsy and a positive lymphocyte transformation test against sulfadoxine, a component of Fansidar, strongly suggest that Fansidar was the cause of hepatic injury. PMID- 2309112 TI - [Results of biliary surgery in a teaching center]. AB - The last few years have seen the introduction of new medical approaches to treatment of gallstone disease. To investigate whether this was the consequence of disappointing results following surgical treatment, we undertook a one-year prospective study at the Clinic of Digestive Surgery in Geneva, a training center with an unselected patient population. From October 1986 to September 1987, 306 biliary operations were performed for calculous disease by 20 surgeons, most of whom were under training. Juniors were supervised by senior surgeons. Operative indications and management were based on the strict criteria established at our center. Over half the patients had suffered one or more complications of gallstone disease. Overall mortality and morbidity were 0.3% and 11.7% respectively. In conclusion, gallstone surgery, which is a definitive treatment, has provided us with very acceptable results and therefore should not be a reason for encouraging other conservative approaches in the treatment of gallstone disease. PMID- 2309113 TI - [At-risk pregnancies--at-risk childbirth]. PMID- 2309114 TI - The asbestos removal fiasco. PMID- 2309116 TI - Dallas AIDS survey raises expectations. PMID- 2309115 TI - Academy sued on "plagiarized" diet report. PMID- 2309117 TI - Democratizing the DNA sequence. PMID- 2309118 TI - Interparticle collisions driven by ultrasound. AB - Ultrasound has become an important synthetic tool in liquid-solid chemical reactions, but the origins of the observed enhancements remained unknown. The effects of high-intensity ultrasound on solid-liquid slurries were examined. Turbulent flow and shock waves produced by acoustic cavitation were found to drive metal particles together at sufficiently high velocities to induce melting upon collision. A series of transition-metal powders were used to probe the maximum temperatures and speeds reached during such interparticle collisions. Metal particles that were irradiated in hydrocarbon liquids with ultrasound underwent collisions at roughly half the speed of sound and generated localized effective temperatures between 2600 degrees C and 3400 degrees C at the point of impact for particles with an average diameter of approximately 10 microns. PMID- 2309119 TI - HTLV-I trans-activator protein, tax, is a trans-repressor of the human beta polymerase gene. AB - Human T cell leukemia virus type I (HTLV-I) is the etiological agent for adult T cell leukemia (ATL). The HTLV-I trans-activator protein Tax can activate the expression of its own long terminal repeat (LTR) and many cellular and viral genes. Tax down-regulated the expression of human beta-polymerase (hu beta-pol), a cellular enzyme involved in host cell DNA repair. This finding suggests a possible correlation between HTLV-I infection and host chromosomal damage, which is often seen in ATL cells. PMID- 2309120 TI - Enhancement of SIV infection with soluble receptor molecules. AB - The CD4 receptor on human T cells has been shown to play an integral part in the human immunodeficiency virus type 1 (HIV-1) infection process. Recombinant soluble human CD4 (rCD4) was tested for its ability to inhibit SIVagm, an HIV like virus that naturally infects African green monkeys, in order to define T cell surface receptors critical for SIVagm infection. The rCD4 was found to enhance SIVagm infection of a human T cell line by as much as 18-fold, whereas HIV-1 infection was blocked by rCD4. Induction of syncytium formation and de novo protein synthesis were observed within the first 24 hours after SIVagm infection, whereas this process took 4 to 6 days in the absence of rCD4. This enhancing effect could be inhibited by monoclonal antibodies directed to rCD4. The enhancing effect could be abrogated with antibodies from naturally infected African green monkeys with inhibitory titers of from 1:2,000 to 1:10,000; these antibodies did not neutralize SIVagm infection in the absence of rCD4. Viral enhancement of SIVagm infection by rCD4 may result from the modulation of the viral membrane through gp120-CD4 binding, thus facilitating secondary events involved in viral fusion and penetration. PMID- 2309121 TI - Calcium-sensitive cross-bridge transitions in mammalian fast and slow skeletal muscle fibers. AB - The fundamental mechanism underlying the differing rates of tension development in fast and slow mammalian skeletal muscle is still unknown. Now, in skinned (membrane-permeabilized) single fibers it has been shown that the rate of formation of the strongly bound, force-producing cross-bridge between actin and myosin is calcium-sensitive in both fast and slow fibers and that the rate is markedly greater in fast fibers. The transition rates obtained at high calcium concentrations correlated with myosin isoform content, whereas at low calcium concentrations the thin filament regulatory proteins appeared to modulate the rate of tension development, especially in fast fibers. Fiber type-dependent differences in rates of cross-bridge transitions may account for the characteristic rates of tension development in mammalian fast and slow skeletal muscles. PMID- 2309122 TI - A voltage-dependent chloride current linked to the cell cycle in ascidian embryos. AB - A voltage-dependent chloride current has been found in early ascidian embryos that is a minor conductance in the oocyte and in interphase blastomeres but that increases transiently in amplitude by more than tenfold during each cell division. Repeated cycles in the density of this chloride current could be recorded for up to 6 hours (four cycles) in cleavage-arrested embryos, whether they were activated by sperm or calcium ionophore. These data suggest that there is a direct link between the cell cycle clock and the properties of this channel, a link that results in pronounced cyclical changes in the electrical properties of early blastomeres. PMID- 2309123 TI - Trends in the geographic inequality of cardiovascular disease mortality in the United States, 1962-1982. AB - Substantial geographic variation of cardiovascular disease (CVD) mortality within the U.S. has been recognized for decades. Analyses reported here address the question of whether relative geographic inequality has increased or decreased during the period of rapidly declining CVD mortality 1962-1982. Trends in geographic inequality, as measured by the weighted coefficient of variation of State Economic Area rates, are analyzed for whites and blacks by sex for 10-year age groups 35-44 to 85 and over. The average annual percent change in the coefficient of variation for each demographic group is presented for all cause mortality, all CVD, stroke and ischemic heart disease. In general, geographic inequalities declined in total mortality for all except the youngest age group. This is consistent with reports of a strong convergence of age-adjusted cancer mortality in U.S. counties. By contrast, increasing geographic inequality dominates in the CVD categories, especially for whites in heart disease and stroke. At younger ages, increases in the coefficient of variation for all race sex groups exceeded 1% per year in stroke and 2% per year in heart disease. These results suggest that factors influencing the percent decline of CVD mortality are not reaching communities of the U.S. equally. Since increases in relative inequality are strongest in the younger age groups, the pattern of inequality may be accentuated as these cohorts move into ages of higher mortality. PMID- 2309124 TI - HIV/AIDS and school boards: a policy approach. AB - In general, there is a low incidence of HIV infection in members of school communities. Moreover, all available evidence supports the conclusion that HIV is not transmitted by the everyday contacts which occur in family, social, employment and educational settings. Despite this, the presence, in a school community, of persons infected with HIV or who have an HIV related disease have been perceived by some as presenting a threat to their children's, and even to their own health and well-being, which, in turn, has led to serious conflicts between various participants in that community. Experience, however, has shown that the fears of many persons and the risks of conflict and confrontation can be minimized, if not negated, if a school board has adopted policies and procedures in relation to HIV/AIDS. Such policies and procedures must be based on current medical knowledge and clearly identified ethical and legal principles, including identification of the rights, interests and needs of all persons and development of appropriate analyses, especially where these are required to resolve conflicts. In this text, educational authorities and their advisors are provided both with a comprehensive model HIV/AIDS policy, and a commentary which examines, amongst other matters, the fundamental ethical and legal considerations which have guided its formulation and the justifications for each of the principles contained therein. PMID- 2309125 TI - Community health workers in Bolivia: adapting to traditional roles in the Andean community. AB - Community health workers (CHW) constitute an outreach program where community members become involved in their health concerns and elect someone to be trained and administer primary health care. A major problem is that CHWs do not fit into leadership roles of either modern or traditional medicine. CHWs of Oruro, Bolivia, are discussed to examine the success of this program in which CHWs adapted to political, economic, and cultural patterns of Andean communities. PMID- 2309126 TI - Prenatal screening of pregnant mothers for parenting difficulties: final results from the Queen Mary Child Care Unit. AB - This paper reports the results of 10 years of research into the prenatal identification of mothers likely to have major parenting problems. Previous published research reported the development of a set of criteria for determining risk status. These criteria were used to classify into four levels of risk a sample of mothers who were consecutive enrollments for prenatal care. The sample was monitored through various social agencies for 2 years. Results of this monitoring indicate the predictive validity of the risk code in an unselected sample. The value of prenatal identification of the 'at risk' is discussed together with the procedures adopted for implementing routine screening in the maternity hospital. The issue of causation, as distinct from prediction, is addressed. PMID- 2309127 TI - Patient outcomes and regional planning of coronary care services: a location allocation approach. AB - We explore the use of patient outcome criteria in planning the locations of critical care health services. Two attributes of the regional distribution of health services which influence health outcomes are: (1) the geographical accessibility of services and (2) the number of patients served by each facility (the patient volume). A model incorporating both factors is developed to determine the number, sizes, and locations of coronary care services in a region in order to maximize patient outcomes. We examine the implications and use of the model in an investigation of the location of coronary care units in rural upstate New York. The results indicate that a system consisting of fewer, well-located coronary care units would be superior for patient survival than the existing system of many dispersed units. Disparities in access to services between urban and rural areas are discussed. PMID- 2309128 TI - Gender differences in tobacco use in Kenya. AB - This study has assessed gender differences in smoking and the use of smokeless tobacco for younger adults and their parents in samples from five ethnic groups in Kenya. These samples were from two groups of pastoralists (the Maasai and the Samburu), a group engaged in fishing and farming (the Luo), and two groups of relatively Westernized Kenyans primarily involved in commercial occupations (from the Kisii and the Gikuyu ethnic groups). In four of the five study groups, there was little or no difference in the prevalence of smokeless tobacco use in either the younger or older generation. Similarly, in four of the study groups there was little or no gender difference in the prevalence of smoking for the older generation. In contrast, for the younger generation in every study group except the Luo, men were much more likely than women to smoke cigarettes. The attitudes toward tobacco use reported by the younger generation showed similar patterns. In every study group except the Luo, the younger adults reported that smokeless tobacco use was socially acceptable for both men and women, but smoking was acceptable only for men. Many of the younger women reported that they did not smoke because it would not be socially acceptable. The interview data suggest that the social prohibition against women's smoking was one component of more general restrictions on women's behavior, and the absence of restrictions on men's smoking was related to men's greater social power. The Luo were the only study group in which respondents reported that women should have as much influence as men in decision making. Correspondingly, the Luo were the only study group in which most respondents considered it acceptable for women to smoke and women were as likely as men to smoke cigarettes. PMID- 2309129 TI - Spiritual and natural etiologies on a Polynesian outlier in Papua New Guinea. AB - Several writers have challenged recently the long-held contention that non Western peoples tend to emphasize spirits, sorcerers, and other supernatural forces in their explanations for the cause of illness. Here, I examine indigenous theories of illness-causation on Nukumanu, a Polynesian outlier atoll in Papua New Guinea. Although Nukumanu invoke mundane as well as supernatural explanations, their major preoccupation is with spirits as etiological agents. In this light, I suggest a number of potential reasons for the difference between my findings on Nukumanu and those of commentators who have emphasized naturalistic etiologies among the peoples they have studied. In addition to real ethnographic variation, I argue that a major reason for the difference lies in the level of causality (instrumental as opposed to efficient and ultimate) sought by various investigators. PMID- 2309130 TI - Breast feeding promotion in an urban and a rural Jamaican hospital. AB - Breast feeding promotion has been a national priority in Jamaica since the mid 1970s. Despite this effort, breast feeding rates have continued to decline there, especially in urban areas. Studies of the role of health professionals in promoting breast feeding have shown that specific practices encourage breast feeding, while others discourage it. In the context of declining breast feeding in a nation committed to promoting it, the goal of this study was to explore the relationship between specific health professional practices, mothers' breast feeding, and mothers' knowledge of breast feeding in rural and urban Jamaica. To accomplish this goal, a structured interview was administered to 113 mothers of infants age 0-6 months at one urban (n = 62) and one rural (n = 51) hospital, regarding (1) physician and nurse practices known to affect breast feeding, (2) mothers' own breast feeding practices, and (3) mothers knowledge of breast feeding issues. Physician and nurse visits were also directly observed to confirm responses given to the questionnaire and to assess the resources devoted to teaching mothers about breast feeding. While extensive lectures, posters and pamphlets promoting breast feeding were provided for mothers at the urban hospital, far fewer educational resources were available for mothers at the rural hospital. Overall, however, health professional practices discouraging breast feeding were observed more frequently at the urban hospital than at the rural hospital, whereas practices promoting breast feeding were more common at the rural hospital. At the rural hospital, mothers' breast feeding practices more closely approximated recommendations than at the urban hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309131 TI - Male and female physicians: family and career comparisons. AB - This article compares career and family characteristics for male and female physicians aged 30-49 in the United States. Despite women's increased presence in the profession, male physicians still out-earn and work more hours than their female counterparts. Males are also more often involved in families than are females. Compared with the U.S. population, male physicians are more likely to marry and parent, while the opposite is true for female physicians. The work family interface also provides dramatic gender differences. Marriage and parenting, which might be expected to impinge on physicians' careers, actually seem to spur men's work commitment and earnings, but have the reverse effect for women. A review of research findings from other industrialized countries reveals similar gender differences in physicians' work and family patterns. The consequence of women's increased presence in the medical profession are discussed in light of these marked gender contrast in work and family life. PMID- 2309132 TI - Determinants of partial participation in the immunization programmes in Iran. AB - Results of 45 cluster sample surveys to evaluate the immunization coverage in Iran during 1986 is reported. Overall, 55% of children between the ages of 12-23 months have complete immunization. Apart from mothers' knowledge and motivations, residence in the rural areas and utilization of antenatal care show positive association with immunization coverage. On the other hand, maternal tetanus immunization, hospital delivery and education of birth attendants for deliveries outside hospital, and the sex of the child do not seem to be associated with the child's immunization status. These and other results are discussed. PMID- 2309133 TI - The structure of readjustment after heart attack. AB - A comprehensive multivariate framework aimed at predicting the factors that enhance or impede readjustment after a heart attack, has been developed and empirically supported by a study among convalescents after heart attack. Application of multivariate techniques of data analysis revealed a 'structure' highlighting the relative weight of various 'demands' in impeding readjustment, and the relative significance of the individual's self-controlled resources in coping with these demands and thus enhance readjustment. The data further show the crucial role of the spouse in both enhancing resources and furthering readjustment. By distinguishing between three dimensions of readjustment--the affective, the instrumental, and the cognitive--the data further the understanding of the differential effects of various demands, resources, and spouse support on readjustment. The herein theoretically justified and empirically supported structure expands the earlier developed structure of readjustment of traumatically irreversible disabled persons, taking into consideration the peculiar situation of the convalescents after heart attack, the trilateral conceptualization of readjustment. PMID- 2309134 TI - Towards a typology of general practitioners' attitudes to general practice. AB - Current knowledge about the origins of variations in general practitioners' (GPs') prescribing and referral behaviour is limited. Differences are as yet unexplained by demographic factors such as list size or geographic location. Drawing on social psychological theory it is suggested that attitudes towards general practice held by GPs may be predictive of GP behaviour. A classification of GP types on the basis of expressed attitudes may represent the first step towards this goal. This research demonstrates that GPs in Avon have identifiable attitudes to general practice which can be classified into separate types. Uses of such a classification and implications for further research are also discussed. PMID- 2309135 TI - Attitudes to AIDS: a comparative analysis of a new and negative stereotype. AB - Two propositions about attitudes, which have previously been supported with respect to the mentally ill, were examined with respect to AIDS patients. The first, that people attach a stigma to the AIDS patient, was strongly supported, and two quite independent components of the stigma were found. One of these components identified as dependence, was closely related to the attributes of typical cancer patients and coronary heart patients, while the other, identified as low moral worth, clearly distinguished the AIDS patient from the other two groups of patients. The second proposition, that attitudes to AIDS are not strongly related to age, sex and occupational background, was largely supported. However there was some evidence that males rated AIDS patients lower on moral worth than did females. PMID- 2309136 TI - Physician utilization and urban native people in Saskatoon, Canada. AB - This paper compares the physician utilization patterns of similarly disadvantaged urban native and non-native people in the western Canadian city of Saskatoon. Through the administration of a large survey instrument to 142 native and 84 non native respondents, the author demonstrates the extensive utilization by native residents of a particular 'walk-in' clinic located in the area which has come to be viewed by many natives as their regular source of medical care. Non-natives, in contrast, demonstrated a greater utilization of physicians in private practice. Beyond the actual location of the physician providing the service, the data demonstrate few differences between natives and non-natives in the extent of their physician utilization. The paper suggests that socio-economic rather than cultural factors better explain the observed patterns of behaviour. PMID- 2309137 TI - Self care--who does best? AB - A clinically evaluated study to assess the benefits of a self care programme in general practice is described. There was significant improvement in psychiatric morbidity at the 6-month follow up, which was maintained at one year. The capacity of Multidimensional Health Locus of Control scales to predict long term clinical improvement was demonstrated, suggesting that a predominantly internal control of reinforcement appears to be crucial to the successful adoption of self care practices. The clinical and educational benefits of such programmes in dealing with a wide range of psychophysical problems in primary care is discussed. PMID- 2309139 TI - Ghost illness in a north Indian village. AB - The substantial number of ghost possessions that came to our attention during fieldwork in a North Indian village in 1977-78 led to a thorough study of ghost beliefs as part of a holistic study of village life. Ghosts are not phantoms floating on the periphery of village life, the concern only of children and the credulous. Rather, the study shows that ghosts are linked with basic Hindu beliefs, village lore, ancient curing practices and theories, the diagnosis of illness and treatment of disease, individual stress and anxiety, and family, lineage, and village histories. Ghost possession, a subsidiary and dramatic form of ghost illness, is behavior in which the ghost speaks from its victim who undergoes a range of alternate states. Unpredictable events and heightened personal stress generally precede episodes of ghost possession. Cases of ghost illness and ghost possession include children and adults of both sexes and a range of ages. Our data contradict the village stereotype that only women suffer from ghost possession. Villagers have recourse to both traditional remedies and Western biomedicine to treat ghost illness. PMID- 2309138 TI - Psychosocial influences on new born outcomes: a controlled prospective study. AB - This paper reports the results of a prospective investigation of 100 women during their pregnancies to test the hypothesis that social and psychological factors influence pregnancy outcome after controlling for demographic, biomedical, and lifestyle variables. Subjects completed questionnaires that assessed family social supports, life events, and anxiety. In addition, data were collected on general biomedical and pregnancy risk, lifestyle practices including smoking and drinking, as well as demographic information. Four infant outcomes, birthweight, gestational age, and 1 and 5 min Apgar scores, were studied via hierarchical multiple regression analyses for their relationship to the social and psychological variables, after controlling for all other sets of variables. The results of these analyses showed that life events stress accounted for significant variation in birthweight, and social supports and anxiety were associated with the two pediatric Apgar scores. Gestational age bore a simple relationship to anxiety, with higher anxiety predictive of lower gestational age. Further analyses revealed that women with either low social supports or high anxiety were, on the average, younger, more often single, of lower education level, had less income, smoked more, and had higher general biomedical risk than women with adequate social supports or lower anxiety. This suggests the multiple ways in which social and psychological risk factors may be related to pregnancy outcome and emphasizes the need for well controlled studies in this area. PMID- 2309140 TI - The relationship of social support and health. AB - The objective of this research note is to challenge the research community to develop a cumulative body of knowledge on the relationship between social support and health. Fruitful approaches to this end include further explication of the concept of social support and its measurement, studies of the causal pathways between social supports and health, and further understandings of the relationship between the different dimensions of support and mental and physical health. PMID- 2309142 TI - Molecular genetics of PKU in eastern Europe: a nonsense mutation associated with haplotype 4 of the phenylalanine hydroxylase gene. AB - Phenylketonuria (PKU) is a genetic disorder secondary to a deficiency of hepatic phenylalanine hydroxylase (PAH). Several mutations in the PAH gene have recently been reported, and linkage disequilibrium was observed between RFLP haplotypes and specific mutations. A new molecular lesion has been identified in exon 7 of the PAH gene in a Hungarian PKU patient by direct sequencing of PCR-amplified DNA. The C-to-T transition causes the substitution of Arg243 to a termination codon, and the mutant allele is associated with haplotype 4 of the PAH gene. The mutation is present in two of nine mutant haplotype 4 alleles among Eastern Europeans and is not present among Western Europeans and Asians. The rarity of this mutant allele and its restricted geographic distribution suggest that the mutational event occurred recently on a normal haplotype 4 background in Eastern Europe. PMID- 2309143 TI - Chromosomal evolution in secretory and nonsecretory subline of MOPC 21. AB - Murine myeloma cell lines are noted for the instability of their immunoglobulin genes and the production of nonsynthesizing variants. In this study, the synthesizing line P3-X63-Ag8 (P3) and its nonsynthesizing subline X63-Ag8-653 (653) were karyotyped and rearrangements of the immunoglobulin carrying chromosomes were investigated. Loss of immunoglobulin synthesis was associated with a reduction in the number of immunoglobulin-carrying chromosomes. When these findings were analyzed in light of published molecular data, it appeared that loss of immunoglobulin synthesis in 653 probably occurred as a result of immunoglobulin gene loss. An unusual finding was the absence of the t(12;15) chromosome in both P3 and 653 cell lines. It was concluded that the t(12;15) chromosome, carried by MOPC 21, has evolved into an unrecognizable form. PMID- 2309141 TI - Driving experience and the risk of traffic accident among motorcyclists. AB - In a case-control study on the risk of traffic accidents among motorcyclists in Singapore, we demonstrated an inverse monotonic relationship between accident risk and driving experience. As compared to drivers with less that 1 yr of driving experience, the odds ratios (adjusted for race, age and frequency of riding) for those with driving experience of 1-4, 5-9 and 10 yr or more were 0.60, 0.50 and 0.36, respectively. We propose that intensive in-circuit training of learner motorcyclists should replace the conventional on-the-road training on the basis that the former serves to increase their driving experience without subjecting the learner motorcyclists to the risk of sustaining road accident. PMID- 2309144 TI - Recent advances in the repair of hypospadias. PMID- 2309145 TI - Cytophotometrically determined DNA content, mitotic activity, and lymph node metastasis in clinical gastric cancer. AB - Analyses of cytophotometrically determined DNA content and mitotic rate were carried out in 37 cases of gastric carcinoma to identify biologic significance of DNA abnormalities. Lymph node metastasis was also evaluated by DNA content and mitotic rate. According to the linear regression analysis, there were statistically significant correlations of mitotic rate with DNA variants such as the peak value, the mean value, and the frequency of cells with values exceeding tetraploid or hexaploid chromosome complement. There were significantly higher values for these DNA parameters in patients with lymph node metastasis compared with those without metastasis. Similarly, higher mitotic rates were observed in tumors with metastatic disease. Thus abnormal DNA fractions appear to be indicative of tumors with a high mitotic activity. The quantitative detection of the DNA abnormalities will provide pertinent biologic information required to predict the occurrence of metastasis in patients with gastric cancer. PMID- 2309146 TI - Severe acute cholangitis: the role of emergency nasobiliary drainage. AB - The role of emergency endoscopic nasobiliary drainage (NBD) in the management of severe acute cholangitis was evaluated by comparing the outcome of 15 patients who underwent the procedure as an initial treatment with that of 20 patients who underwent emergency surgery. Biliary sepsis was successfully controlled without complication in all 15 patients by the insertion of a 7F nasobiliary catheter through a limited papillotomy. Subsequent definitive elective treatment included endoscopic stone clearance (n = 6), common duct exploration (n = 8), and bili enteric reconstruction (n = 1). Among the 20 patients who had surgical treatment, cholecystectomy (n = 11), cholecystostomy (n = 1), and transhepatic intubation (n = 1) were done in addition to common duct exploration. Although patients undergoing endoscopic NBD were significantly older (75.3 years vs 60.1 years; p less than 0.05) and more jaundiced (total bilirubin, 120.3 mmol/L vs 70.4 mmol/L; p less than 0.05), comparable morbidity (40% vs 65%) and mortality (6.7% vs 20%) was observed. Initial endoscopic NBD provides a safe and effective therapeutic option for the management of fulminant biliary sepsis. Among patients with complicated ductal anatomy, endoscopic NBD should first be attempted because, when successful, definitive reconstruction may be performed on an elective basis. The value of its routine application for all patients, however, remains to be validated by further clinical studies. PMID- 2309147 TI - Prognostic implications of postoperative suppression of arterial ketone body ratio: time factor involved in the suppression of hepatic mitochondrial oxidation reduction state. AB - To determine the tolerance limit of the liver in the critically suppressed mitochondrial oxidation-reduction state, the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), which reflects hepatic mitochondrial oxidation reduction potential, was measured 1319 times in 161 patients during the postoperative critical period. Because patients who showed arterial ketone body ratios between 0.40 and 0.25 had a higher incidence of postoperative complications than had those who showed ratios above 0.40, this was designated as the critical zone of the arterial ketone body ratio. When duration in the critical zone was less than 2 days, 90% of the patients were able to tolerate the condition and survive. By contrast, when an arterial ketone body ratio below 0.40 was prolonged for more than 5 days, there was a high incidence of multiple organ failure and a 100% mortality rate, with the average survival period after a 5-day suppression being estimated as 5.7 +/- 2.4 days. It is suggested that the arterial ketone body ratio in the critical zone must be returned to normal values within 2 days to obtain a good prognosis. PMID- 2309148 TI - Hepatic blood flow and splanchnic oxygen consumption measurements in clinical sepsis. AB - In an effort to characterize the hemodynamic response of the liver to sepsis, hepatic blood flow (HBF) was measured in 10 normal volunteers and compared with that of 9 patients with sepsis. Flow was determined according to two different indicators and three methods of analysis including indocyanine green dye clearance (HBFICG), galactose clearance (GC), and galactose clearance with splanchnic galactose gradient measurement (HBFGG). For normal subjects, these three analytic methods provided essentially identical results (HBFICG = 0.74 +/- 0.18, GC = 0.72 +/- 0.14, and HBFGG = 0.76 +/- 0.16 L/min-m2). With hepatic venous sampling, HBF in patients with sepsis was significantly higher than normal levels (HBFICG = 1.28 +/- 0.50 and HBFGG = 1.17 +/- 0.52 L/min-m2) (p less than 0.025), but HBF by the GC technique (0.89 +/- 0.41 L/min-m2), which uses peripheral venous sampling, was not significantly increased because of reduced splanchnic galactose extraction, which appears to be characteristic of sepsis. Thus HBF estimates based on peripheral venous sampling must be interpreted with caution in view of the reduced extraction fraction in sepsis. HBF in clinical sepsis tends to increase in response to this inflammatory stress. PMID- 2309149 TI - Pericystectomy for the treatment of hepatic hydatid cysts. AB - Management of the pericystic membrane is still a major problem in the treatment of hepatic hydatid disease. In a series of 23 patients with 45 cysts, complicated forms constituted 51% of all cysts. Radical removal, mainly by pericystectomy, was achieved in two thirds of cysts and in 50% of cases. Pericystectomy, if carried out in the correct plane of cleavage, is a safe procedure that ensures complete and rapid cure in appropriately selected cases. PMID- 2309150 TI - Cutaneous thermal injury alters macromolecular permeability of rat small intestine. AB - The intestinal epithelium normally provides a barrier function that prevents absorption of potentially harmful materials from the intestinal lumen. It has been postulated but never demonstrated that a cutaneous thermal injury will result in increased small-intestinal permeability. In a standardized 20% body surface area full-thickness scald injury, with polyethylene glycol 3350 and horseradish peroxidase used as permeability probes, small-intestinal permeability was examined regionally in an everted intestinal sac model. In the normal animals, the upper (proximal) and lower (distal) small intestine were less permeable to these probes than the middle segment. Within 6 hours after the injury, an increase in the mucosal uptake and transmural permeability was seen in all three small-intestinal segments; the most dramatic increase in permeability occurred in the ileum, p less than 0.01. The maximum increase in permeability was seen at 18 hours, and permeability was normal by 72 hours after the injury. This increase in intestinal permeability may represent a transient failure of the intestinal barrier function and may allow absorption of potentially toxic macromolecules from the intestinal lumen into the portal circulation early after thermal injury. Absorption of these macromolecules, such as endotoxin, may be potentially harmful by direct toxic actions or potentially helpful by activation of the immune system. PMID- 2309151 TI - Superior mesenteric vein inflow for liver transplantation when the portal vein is occluded. AB - An alternative solution to the problem of liver transplantation in the patient with an occluded portal vein is described. It uses a bridge graft of donor iliac vein from the superior mesenteric vein at the base of the colonic mesentery. The graft is tunnelled over the pancreas and under the stomach to the region of the liver hilum to provide portal inflow. This procedure was employed successfully in four patients, with patency for more than 2 years in the patient with the longest follow-up. By this approach it is routinely possible to perform a transplant procedure in a recipient with an occluded portal vein. PMID- 2309152 TI - Vascular reconstruction after extended resection of a retroperitoneal fibromatosis. AB - We report the case of a 25-year-old man who underwent successful en-bloc resection of a retroperitoneal fibromatosis, extended to the right kidney and testis, with excision of the right iliac arteries and veins. Arterial replacement was done by means of a right iliofemoral prosthetic graft. A right femorocaval prosthetic graft with a temporary arteriovenous fistula was used for venous replacement. The patient is still alive and after 3 years shows no sign of recurrence on successive computed tomographic scans. He has preserved patency of the right arterial and venous iliac grafts. To our knowledge, this is the first documented case of simultaneous arterial and venous iliac replacement successfully performed after excision of a retroperitoneal tumor. PMID- 2309153 TI - Isolated iliac vein injury from blunt trauma. AB - A case of isolated iliac vein disruption from blunt abdominal trauma is described. Hypotension and the presence of a massively swollen lower extremity suggested the diagnosis. Dissection of the femoral vein allowed us to use venography to delineate the injury and to gain proximal inflow control. A 4 cm longitudinal tear of the external iliac vein was identified and repaired. No other cases of isolated iliac vein injury from blunt trauma could be identified. PMID- 2309154 TI - Intraoperative removal of pancreatic duct calculus with a rigid ureterorenoscope and ultrasonic lithotripsy. AB - A 51-year-old man with chronic relapsing pancreatitis and recurrent episodes of acute attacks had an impacted ductal stone deep in the head of the pancreas. A staghorn calculus, 1 cm in diameter, was successfully disintegrated and removed intraoperatively with use of a visual endourologic technique and ultrasonic lithotripsy. Because of a dilated pancreatic duct and pseudocyst formation near the tail of the pancreas, distal pancreatic resection and longitudinal pancreaticojejunostomy were performed. Postoperatively, no pancreas irritation has been verified, and the patient has remained without symptoms. PMID- 2309155 TI - Massive hemoperitoneum from transhepatic perforation of gallbladder. PMID- 2309156 TI - Axillary compression syndrome. PMID- 2309157 TI - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in the rat: characterization and age-dependent effects. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent dopaminergic toxin that has been found to produce Parkinson's disease-like symptoms in humans and monkeys. The neurotoxic effects of MPTP appear to be reduced in rodents where multiple dosing procedures are required to demonstrate long-lasting neuronal deficits. In the present study, the neurotoxic effects of MPTP were further characterized in the rat. Following the repeated administration of MPTP, pronounced (60-80%) and dose-dependent depletions of striatal dopamine and serotonin concentrations were found in the rat brain. Time-course studies revealed that while striatal dopamine concentrations remained consistently reduced for at least 8 weeks following MPTP treatment, striatal serotonin depletions as well as MPTP-induced monoamine depletions in other brain regions were transient in nature. Pretreatment with the MAO-B inhibitor pargyline afforded a selective and complete protection of striatal dopamine levels without significantly affecting MPTP-induced striatal serotonin depletions. Similarly, treatment with ascorbic acid was found to selectively attenuate MPTP-induced dopamine depletions in rats. The neurotoxic effects of MPTP were also found to increase in the developing rat. No significant brain monoamine depletions were observed in neonatal rats following the repeated administration of MPTP. However, MPTP-induced neurotoxicity progressively increased in older rats. The present results indicate that when appropriate treatment procedures are used, a pronounced, selective, age-dependent, and long-lasting MPTP-induced reduction in striatal dopamine concentrations can be observed in the rat brain. The present results are discussed in reference to the putative mechanisms and species differences of MPTP-induced neurotoxicity. PMID- 2309158 TI - Morphological correlates of long-term potentiation imply the modification of existing synapses, not synaptogenesis, in the hippocampal dentate gyrus. AB - This report evaluates two morphological markers of synaptogenesis following the induction of long-term potentiation (LTP) in the dentate gyrus of the anesthetized rat. These two morphological features, polyribosomes and multiple synaptic contacts, are known to increase in number with synaptogenesis in the mature hippocampus. The analysis focused on the middle third of the dentate molecular layer. As shown previously, this is the region of primary synaptic activation in our electrophysiological protocol and the region of localized morphological changes with LTP. Here the incidence of a polyribosome at the base of a dendritic spine declined 57% with LTP. In addition, the number of multiple synaptic contacts decreased 18% there with LTP. Both decreases were more pronounced immediately following conditioning stimulation than at later intervals. Because both morphological features decrease with LTP but increase with synaptogenesis, the data do not support the hypothesis that new synapses form with LTP. Instead, the data add further support to the view that the strengthening of existing excitatory synapses underlies LTP. PMID- 2309159 TI - Direct effect of 17 beta-estradiol on striatum: sex differences in dopamine release. AB - The nigrostriatal dopamine (DA) system is sexually dimorphic. In female but not male rats, striatal DA activity is modulated by gonadal steroid hormones. Ovariectomy (OVX) decreases striatal DA release and turnover. Estrogen replacement restores the response to that of the intact female in estrus. In contrast, castration (CAST) of male rats has no effect on the stimulated release of DA from striatal tissue. This report addresses the question: Does estrogen act directly on the striatum to induce changes in DA release? Physiological concentrations of 17 beta-estradiol and other steroids or a nonsteroidal estrogen analog were applied directly to striatal tissue maintained in an in vitro superfusion system. The effect of hormonal treatments on the responsiveness of striatal DA terminals to stimulation was examined in tissue from OVX females and intact and CAST male rats. The results are summarized as follows: (1) Infusion of 17 beta-estradiol (p less than 0.01) and diethylstilbestrol (p less than 0.05) increased amphetamine (AMPH)-stimulated striatal DA release from striatal tissue of OVX female rats compared with the effect of cholesterol. 17 alpha-Estradiol also tended to potentiate the striatal DA response to AMPH, but this result was not statistically significant (p less than 0.062). 17 beta-Estradiol had no effect on AMPH-stimulated DA release from striatal tissue of intact male rats. (2) The KCl-stimulated release of DA from striatal tissue of OVX rats exposed in vitro to 100 pg/ml 17 beta-estradiol (a physiological dose) was significantly greater (p less than 0.05) than the response after exposure to vehicle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309160 TI - Nigrostriatal lesion alters neurophysiological responses to selective and nonselective D-1 and D-2 dopamine agonists in rat globus pallidus. AB - The effects of the selective D-1 dopamine agonist SKF 38393, the selective D-2 agonist quinpirole, and the nonselective D-1/D-2 agonist apomorphine on spontaneous activity of globus pallidus neurons were compared in normal control rats and rats with unilateral 6-hydroxydopamine induced lesions of the nigrostriatal pathway. In control, unlesioned rats, SKF 38393 (0.4 and 10 mg/kg, i.v.) caused no significant net change in the activity of globus pallidus neurons, although some individual cells showed significant increases or decreases in discharge rates following 10 mg/kg SKF 38393 administration. In animals with unilateral 6-hydroxydopamine induced lesions, SKF 38393 caused greater increases and decreases in the discharge rates of a larger percentage of pallidal cells recorded on the ipsilateral side than in control, unlesioned animals. These rate changes were effectively reversed by the D-1 antagonist SCH 23390, but not by the D-2 antagonist YM-09151-2. Quinpirole (0.3 mg/kg, i.v.) produced modest rate increases in control, unlesioned animals and significantly larger rate increases in nigrostriatal lesioned animals. YM-09151-2, but not SCH 23390, effectively reversed quinpirole's effects in the lesioned animals. As previously reported, the nonselective D-1/D-2 agonist apomorphine (0.3 mg/kg, i.v.) produced large increases in discharge rates of pallidal cells in control, unlesioned rats. In contrast, in nigrostriatal lesioned rats, the discharge rates of some ipsilateral pallidal neurons were markedly increased, others were decreased, and some were unaffected following apomorphine administration. The dopamine antagonist spiroperidol partially to fully reversed these rate changes. In summary, apomorphine's neurophysiological profile appears to be an exaggeration of the D-1 agonist profile in the globus pallidus of these lesioned animals. The degree of change observed after apomorphine administration is consistent with results from other studies that have indicated that a synergistic interaction between effects triggered by stimulation of the two receptor subtypes can occur in these animals, as in control, unlesioned animals. However, these results further show that in rats with unilateral nigrostriatal lesions, the denervated dopamine receptors or the processes they mediate are altered so that they no longer have the requirement seen in controls for concurrent stimulation of the complementary dopamine receptor subtype for expression of the selective agonist effects. PMID- 2309161 TI - Gallstones and obesity: observations from 352 autopsied patients. AB - Obesity has been considered a risk factor for gallstones, but the association remains controversial. To test this possible association we studied autopsy reports of 352 adult patients. These included 248 obese and 104 non-obese patients. The body mass index, defined as body weight in kg/m2, was used to assess and measure the degree of obesity and to divide patients into two groups: Group 1 (normal weight and mildly obese individuals) and Group 2 (moderately and severely obese individuals). The comparative frequency of gallstones in these two groups was statistically analyzed by the Mantel-Haenzel method with stratification for age, sex, and diabetes mellitus. No significant association between gallstones and obesity (p less than 0.2) was found. PMID- 2309162 TI - Childhood and adolescent cancer in a southwestern region of Texas: 1976-1980. AB - The Cancer Registry Division of the Texas Department of Health identified 349 malignant tumors among Anglo and Hispanic children and adolescents less than 20 years of age who lived in a southwestern region of Texas during the period 1976 1980. The ethnic distribution of cases consisted of 184 Anglos (53%) and 165 Hispanics (47%). The total cancer incidence rate per million for Anglos was 198.2 for males and 141.2 for females; for Hispanics the rate was 130.7 for males and 142.0 for females. The rates for all sites combined were higher for Anglo males than for US white (Anglo and Hispanic) males. Anglo females, Hispanic males, and Hispanic females had all sites combined rates that were similar to the rates for US white males and females. Anglo males were at increased risk for brain/central nervous system and kidney tumors. Leukemia was the most frequent cancer seen. All ethnic/sex groups were at increased risk for leukemia; however, only females had significantly higher rates. PMID- 2309164 TI - Preventing child abuse and neglect in Texas. AB - The rising prevalence of child abuse and neglect in Texas underscores the need to encourage innovative programs across the state. Primary prevention efforts catalyzed by the Children's Trust Fund of Texas demonstrate such projects. Specific evaluation techniques are also reviewed with some explanation of why some programs may be more effective than others. PMID- 2309163 TI - Thiopental attenuates dysrhythmias in children: comparison of induction regimens. AB - Anesthesia was induced in 91 children using one of three induction regimens: (a) thiopental, atropine, and succinylcholine (T group); (b) halothane, atropine, and succinylcholine (H group); and (c) halothane, thiopental, atropine, and succinylcholine (H/T group). The incidence of dysrhythmias was significantly greater in the H group (85%) than in the T group (6%) and H/T group (20%). Fewer dysrhythmias occurred in the H/T group compared to the H group despite similarly prolonged QTc intervals in both groups. We conclude that induction of anesthesia with thiopental is appropriate and reduces the incidence of cardiac rhythm disturbances in children and that administration of thiopental to children during induction of anesthesia with halothane, atropine, and succinylcholine may reduce the incidence of cardiac dysrhythmias. PMID- 2309165 TI - New peer review reporting and disclosure requirements--Part I. AB - This article reviews the reporting and disclosure provisions of the Health Care Quality Improvement Act of 1986, the Medicare and Medicaid Patient and Program Protection Act of 1987, the Texas Medical Practice Act, and federal regulations promulgated in late 1989 to establish the operating rules and policies of the National Practitioner Data Bank. A table on pages 56-57 outlines the reporting requirements of these laws and regulations. Discussion focuses on the requirements the new federal regulations place on physicians and other health care practitioners, health care entities, and insurers. PMID- 2309166 TI - Let's revive hospital medical risk management programs. PMID- 2309167 TI - [Experiences after the Chernobyl accident]. PMID- 2309168 TI - [Hospital infections]. PMID- 2309169 TI - [How hazardous is cesarean section?]. PMID- 2309170 TI - [Alcohol]. PMID- 2309171 TI - [Kidney transplantation]. PMID- 2309172 TI - [Kidney transplantation in Norway]. AB - Twenty years ago, in 1969, a national kidney transplant program was established, based on uniform indications and preparations for transplantation. Since 1983, all transplants have been performed at one centre. We describe the organization, development, treatment policies and results of the program. The national transplant rate of 42 patients per million population per year (p.m.p.) keeps up with the demand. In contradiction to the international experience of rapidly expanding waiting lists and dialysis populations, a balance has been achieved in Norway, with a high transplant rate, a restricted and stable waiting list (mean 23 p.m.p.), waiting time (mean 5 months) and dialysis population. Approx. 80 per cent of all patients requiring long term renal replacement therapy actually receive a transplant, as against approx. 50% in Western Europe. Seventy-five to 100 per cent of the transplants function for more than a year, and 55-80 per cent for more than five years, depending on the donor and HLA compatibility. Other significant risk factors are age and HLA sensitization. Since 1983, 46 diabetics with renal failure have been treated by combined renal and pancreatic transplantation. PMID- 2309173 TI - [Treatment of chronic kidney failure with dialysis and transplantation. Development, need and organization in Norway]. AB - Treatment of chronic renal failure by dialysis and renal transplantation has been developed over the last 20 years in Norway. 17 local nephrological units with dialysis departments cooperate with one transplantation center in Oslo. The number of new patients starting renal replacement therapy has increased only slightly during the last five years. The mean number of new patients in the period was 52 per million inhabitants per year. The proportion of elderly patients accepted for renal replacement therapy was high (39% above 60 years of age) and approximately 15% of the patients had diabetic nephropathy. Due to an active transplantation policy, the proportion of patients alive on dialysis is low (18%), compared with 82% alive with a functioning graft. The number of patients on dialysis has declined slightly the last four years. The proportion of patients on chronic ambulatory peritoneal dialysis (CAPD) is low (13%), and the number of patients on home hemodialysis has declined in the last five years. Predialytic transplantation has been performed in 18% of the patients starting renal replacement therapy during the last five years. Due to a high transplantation rate and a large number of predialytic transplantations, it has not been necessary to increase the capacity for dialysis in the last five years. PMID- 2309174 TI - [Organ donations from recently decreased donors]. AB - Annually there are slightly more than 50 cadaveric donors in Norway. This corresponds to an average rate of 12.4 donations per million inhabitants per year during the period 1985-88. This does not meet the demand for hearts, livers, and kidneys for transplantation. In Norway, only a fraction of patients who die of disease leading to brain death become cadaveric donors. There are striking and unexplained differences in donation rates between regions. We discuss strategies to improve the supply of cadaveric organs. PMID- 2309175 TI - [Costs of care in uremia. How much does kidney transplantation cost?]. AB - The cost of kidney transplantation and hemodialysis have been recorded (in 1986). Tissue typing, operation and initial stay in hospital cost NOK 103,000 per patient, and further treatment for the first year after operation NOK 114,000. Subsequent annual costs were NOK 70,000, mainly for drugs. Hemodialysis costs NOK 287,000 per year. Transplantation was cost-effective by almost NOK one million per patient over a five-year period. If the current high national rate of transplantation (42 patients per million), which keeps both the national waiting list (23 patients per million) and the dialysis population at a low level, is sustained over the next five years, then total national expenditures for dialysis and transplantation are predicted to be approx. NOK 400 millions. If no transplants were performed during this period the waiting list would increase to 175 patients per million, and expenditures (for dialysis) to approx. NOK 750 millions. Additional huge investments would be needed in order to expand the facilities for dialysis. Because of high transplant rate, only 18 per cent of all treated uremics in Norway are now on dialysis, versus 73 per cent in Western Europe. Since transplantation is much cheaper than dialysis, national expenditures per treated patient are lower in Norway than in any other country. PMID- 2309176 TI - [Enterobacter cloacae infections at the Regional Hospital in Tromso]. AB - Enterobacter cloacae was isolated from 69 patients hospitalized at the University Hospital of Tromso, Norway, during a period of 18 months. The total lethality was 11.6% (8/69) and death occurred most often in patients with a serious underlying condition. Death due to septicaemia occurred in 4/10 patients. Multiple beta lactam resistant strains were present in 15 patients and were associated with septicaemiae (7/10, p less than 0.0005). Cephalosporin treatment had been given to every third patient (24/69), and nearly half of them (10/24) were infected by multiple beta-lactam resistant E cloacae. E cloacae occurred mainly as a nosocomial infection, since more than 70% of all patients infected had been treated by an invasive procedure prior to isolation of the bacterium. A high number of E cloacae strains were from operation wounds, especially among patients at the Department of Surgery (22/30). At this Department, the total number of E cloacae, and especially the number of multiresistant strains, was markedly reduced during restricted use of cefalosporins. PMID- 2309177 TI - [Preventive antibiotics in emergency cesarean section. A prospective comparison of benzylpenicillin and ampicillin plus cloxacillin]. AB - Emergency cesarean section, especially when performed more than ten hours after rupture of the membranes, involves a high risk of postoperative infection. Different antibiotic regimens have been shown to reduce these infections substantially. In this prospective study a combination of ampicilling (2 g) plus kloxacillin (2 g) given as a single-dose infusion directly after division of the cord reduced the post-operative infection rate to 13% in a group of high-risk emergency cesarean section cases. Benzylpenicillin only (2 g) was less efficient. No side-effects were observed, and this prophylaxis may have certain advantages over cephalosporins, especially with respect to enterococcus-induced endometritis. PMID- 2309178 TI - [Complications following cesarean section]. AB - During a seven-years period, 898 women (9.9% of all deliveries) had a cesarean section at the Department of Obstetrics and Gynecology, University Hospital of Tromso. 29.3% of the women suffered one or more complications (8.5% intraoperative, 23.1% postoperative). The most common complication was infection (22.3%). The following factors were associated with the occurrence of complications: emergency operation, obesity, labor prior to surgery, increased duration of labor or rupture of fetal membranes prior to operation, low gestational age, and station of the presenting part of the fetus below the ischial spinal plane. The same tendency was found for intra- and postoperative complications. Hb levels less than 12.0 g/100 ml increased the risk of infection. We suggest ways of reducing both the number of cesarean sections and the number of complications. PMID- 2309179 TI - [Children with congenital heart defects in Vestfold 1982-88. Increase in the incidence resulting from improved diagnostics methods]. AB - In the population of live born children in the County of Vestfold, Norway, during the seven-year period 1982-88 (N = 15,307), 138 cases of congenital heart defects were diagnosed (patent ductus arteriosus in preterm infants excluded), an incidence of 0.9%. In 114 infants (83%) the defect was diagnosed before discharge from hospital after birth (nursery, neonatal unit), in 20 infants (14%) it was diagnosed later during the first year of life, and in four (3%) during the second year of life. In 24 children (17%) congenital heart defect was associated with a syndrome (Down syndrome eight, Edwards syndrome three, other syndromes three), or other congenital malformations (single eight, multiple two). Diagnosis was made clinically only (including ECG, phonocardiography and X-ray pictures) in 15 patients (11%). 13 were classified as having ventricular septal defects, and two were unclassified. Echocardiography was performed in 120 children (87%), heart catheterization in 44 (32%), surgery in 47 (34%), and autopsy in 12 (9%). 15 children (11%) died, all during the first year after birth. 45 children (33%) are healthy after spontaneous closure of a ventricular (41 children) or atrial septal defect (four children), and 15 (11%) after surgical repair. 63 (46%) are alive with a defect. We found a tendency towards increasing incidence of congenital heart defects. This increase was explained by echocardiographic diagnosis of small muscular ventricular septal defects in the early neonatal period, with spontaneous closure of the defect during the first year of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309180 TI - [Pregnancy outcome in some Norwegian counties before and after the Chernobyl accident]. AB - The outcome of pregnancies in six countries in Norway has been studied during 12 months prior and subsequent to the Chernobyl accident. The accident took place in a period with an annual increase of births of approximately 3%. However, the year after the accident a decrease of 0.7% was observed with particularly low numbers during February--April 1987. Concomitantly, the miscarriage fraction of all pregnancies increased by 16.3% and particularly during November 1986--January 1987. The same pattern was found when observations from Haukeland Hospital were analyzed separately. When the time of conception was taken into consideration we found that conceptions during the period May--July 1986 ended more often as miscarriages. We have no explanation of the observations. The external radiation exposure seems too small to have produced these effects. The internal radiation from food may have played a role. People may also have changed their food intake, using less vegetables, due to fear of these being polluted by radioactive fallout. PMID- 2309181 TI - [Magnetic tomography at Rikshospitalet]. AB - During the first 18 months of operation of the magnetic resonance unit at Rikshospitalet, 1,453 MR examinations have been performed on 1,431 patients. 64% of the time has been devoted to examinations of the central nervous system and spine in children and adults, nine % of the time has been used on non neuroradiology pediatric patients, while the rest of the time has been spent equally on ear, nose and throat, thoracic (including cardiac) and abdominal examinations in adult patients. The indications for doing MRI at Rikshospitalet are listed and discussed, and it is concluded that MRI has proved to be useful at several conditions in most organ systems. However, the capacity of our single MR unit is much smaller than the need for examinations. The author discusses reasons. PMID- 2309182 TI - [Body temperature measurement. A comparison of rectal measurement using a mercury thermometer with oral axillary measurement using a new electronic thermometer]. AB - New methods for measuring body temperature are marketed regularly. In our department we used an electronic thermometer (Craftemp) which measured oral or axillary temperature. Since we doubted the accuracy of the measurements made with this device, we compared the values found using this thermometer with values from a conventional mercury thermometer, both in a thermostatic regulated water bath and when used clinically. There was good conformity between the results in the water bath. However, when the thermometer was used clinically, in half the patients there was a difference of 0.5 degrees C or more from the rectal temperature measured with a mercury thermometer. Most of the beds in our department are occupied by geriatric patients with age-related diseases. Many of them also have mental disturbances (e.g. dementia), which makes adequate cooperation during the measuring procedure uncertain. This study indicates that the electronic thermometer (Craftemp) is not suitable in a department like ours with many old disabled patients. PMID- 2309183 TI - [Trends in alcohol-related damages in Norway]. AB - Like most other countries Norway has experienced a substantial increase in alcohol consumption since world war II, particularly in the 1960s and 1970s. This development has been accompanied by an increase in the prevalence of heavy drinkers, and an increase in the frequency of drunkenness. The effects on mortality rates have been substantial. It is estimated that alcohol-related mortality from diseases due to long-term abuse have increased fourfold since world war II. Violent deaths due to alcohol intoxication have increased too. Furthermore, the increase in crimes of violence experienced after the mid-1960s is partly due to the increase in alcohol consumption. PMID- 2309184 TI - [Alcohol-related admissions to a district hospital]. AB - This is a retrospective study of alcohol-related admittances to the medical department of Molde District Hospital. All cases with certain diagnoses where alcohol is mentioned as a possible cause were recorded, and compared with a reference group of matched, non-alcohol-related cases. During the period 1980-86, 228 patients were admitted 350 times to the medical wards of the hospital. These patients had a significantly higher number of admittances than the reference patients, both to the medical ward and to other wards. They also had a higher frequency of emergency admittances. The average age of patients admitted for alcohol-related causes was much lower than that of the general patient population. The relative number of recorded alcohol-related admittances to the medical ward increased over the seven year period, from 3.8 to 5.5% for men and from 0.7 to 1.6% for women. PMID- 2309185 TI - [Duplex examination of the carotid artery]. AB - Duplex sonography is an accurate and non-invasive method of detecting carotid arterial disease. It has a good sensitivity and specificity for detection of stenosis and ulcerations. It is preferred as the primary investigation when atherosclerotic disease of the carotid artery is suspected. The method is reviewed briefly and the results of eight months use referred. PMID- 2309186 TI - [Diagnosis of dementia]. PMID- 2309187 TI - [Injuries among soccer players in lower division clubs]. AB - Soccer is said to cause frequent injuries among players in lower division clubs. We therefore followed three teams for 17 months, and registered all training and match activities. We registered several risk factors associated with a prevalence of injuries. Our records indicate moderate incidence of injuries, few serious injuries, minimal absence from school and work because of the injury, and insufficient use of protective equipment by the injured players. PMID- 2309188 TI - [Health protection after the Chernobyl accident. The relation of costs and reduction of radioactive dosage level]. AB - This article describes the nutritional measures introduced to protect health after the Chernobyl accident, and the associated costs. The total value of the reindeer meat, mutton, lamb and goat meat saved as a result of such measures in 1987 amounted to approx. NOK 250 million. The measures cost approx. NOK 60 million. The resulting reduction in the radiation dose level to which the population was exposed was 450 manSv. In 1988, mutton/lamb and goat meat valued at approx. NOK 310 million was saved from condemnation by similar measures, which cost approx. NOK 50 million. The resulting dose level reduction was approx. 200 manSv. The relationship (cost/benefit ratio) between the overall cost of the measures taken to reduce radioactivity levels in food and the dose level reduction achieved was acceptable. PMID- 2309190 TI - [Professional competence of the notification service]. PMID- 2309189 TI - [From social medicine to public health science]. PMID- 2309191 TI - [Life with and without Halcion]. PMID- 2309192 TI - [Hemostasis in hemorrhagic peptic ulcer]. PMID- 2309193 TI - [Medical or surgical castration in prostatic cancer? Experience of 100 orchiectomies]. AB - The mean age of 100 patients who underwent orchiectomy for carcinoma of the prostate was 76.4 years. 50% of the patients had distant metastases. Almost all had a locally advanced tumour. 49 patients were operated by orchiectomy only. On 51 occasions, a transurethral resection of the prostate was carried out under the same anesthesia. In 22 patients, operation of the prostate was done without previous planning, "because the patient was already on the operating table". Mean stay in hospital varied from 11.2 to 15.6 days, depending on the extent of the operative treatment. Social factors were the most important reason for prolonged hospitalization. Patients who are offered castration in the treatment of prostatic cancer have a great latent need for medical service and social care. PMID- 2309194 TI - [Incidence of extrauterine pregnancy in Norway in 1986. A population based overview from 15 counties]. AB - Hospitalization for ectopic pregnancy was examined in 15 out of 19 Norwegian counties in 1986. The incidence of ectopic pregnancy was 1.5 per 1,000 women aged 15-44 years. The incidence was highest in the five northernmost counties and Oslo. Women aged 25-34 years, who had the highest rate of conception, also had the highest rate of ectopic pregnancy. Measured as a ratio per 100 live births, ectopic pregnancy increased with the patient's age and was six times as high among women aged 35-44 compared to women aged 15-24. The overall ratio was 2.5 ectopics per 100 live births. The age-specific rates and ratios were consistent with varying overall incidence of ectopic pregnancy in the counties. PMID- 2309195 TI - [Injuries in handball players]. AB - The study involves 421 patients who had suffered injury while playing handball. It describes mechanism and trauma, the injuries and their consequences, and data on training and technical conditions. 2/3 of the injured were female and one half belonged to the younger age-classes. The incidence of injury was highest among senior players. Distortion was the most frequent type of injury, followed by contusions and fractures. Half of the injuries were to the upper limbs, but the most frequent single injury was injury to the ankle joint. Many fractures were seen in fingers, forearm, hand and ribs. Wounds occurred most frequently to the face. The most serious injuries were ruptures of the ligaments in the knee joint. Protective equipment, such as braces, was seldom used. A small minority of the players were given adequate first aid. Important measures to prevent injury include better basic training, better technical training conditions, good first aid, and some changes in the rules of competition. PMID- 2309196 TI - [The back and neck in healthy young Norwegians. A radiologic examination of the spine of 232 applicants for air force pilot education]. AB - Neck pain and neck injuries are common complaints among aviators flying modern fighter aircraft. For this reason all candidates for military flying training in the Air Force have to undergo a radiological examination of the spine as part of the selection procedure. Nine films are produced, with particular emphasis on cervical structures. Altogether 527 positive findings were made among 232 applicants, an average of 2.27 diagnoses per x-rayed spine. Since the candidates had been medically screened prior to the radiological examination, it is not unlikely that the results reported in this highly selected group represent minimum figures for young adult Norwegians. PMID- 2309197 TI - [Furosemide capsules in the treatment of hypertension or heart failure in the elderly in general practice]. AB - The article reports the efficacy and tolerability of a new slow-release formulation of furosemide (Lasix Retard) given to an elderly (mean: 72 years, range 48-92) population (n = 115, 77 females) suffering from hypertension or heart failure. In 34 of 52 patients with heart failure the clinical condition improved. Lasix Retard reduced blood pressure significantly from 187/99 to 166/93 after one year on 30 mg/day (n = 19). It was found that Lasix Retard replaces thiazide diuretics without causing any significant change in blood pressure. There were no significant changes in metabolic indicators (S-potassium, S-urate, S-glucose). Side effects were in the same range as reported for thiazide diuretics. There were 33 (29%) drop-outs. PMID- 2309198 TI - [Chloroquine poisoning]. AB - Chloroquine poisoning has profound effects, chiefly on contractility and conduction of the heart. No treatment has been proven effective, and most cases of serious poisoning are fatal. We describe one case of chloroquine poisoning and discuss its treatment. PMID- 2309199 TI - [Use of pleuradren]. PMID- 2309200 TI - [Occupational physicians' roles and ethics]. AB - Occupational physicians work in close contact with individuals and groups within an organization. Professional secrecy is best taken care of by defining the different tasks as physician/patient relationship, adviser and expert. The occupational physician is independent in medical issues. When necessary he should influence the process of decision in the organization, but be loyal when a decision is final. In the event of conflicts between an individual and the organization concerning medical issues, he should consider the interests of the individual. Knowledge and awareness of social legislation is essential. PMID- 2309201 TI - [Cooperation between the general practitioner and occupational physician]. PMID- 2309203 TI - [Contact lenses]. PMID- 2309202 TI - [Manipulation treatment by physicians, physiotherapists and chiropractors]. PMID- 2309204 TI - [Continent urostomy using Kock's method]. PMID- 2309205 TI - [Renewed interest in Thorkildsen's operation]. PMID- 2309206 TI - [Urothelial carcinoma of the upper urinary tract. 10 years' material from a central hospital]. AB - During the last ten years, 16 patients have been treated for urothelial carcinoma of the upper urinary tract, ten carcinomas of the renal pelvis and six carcinomas of the ureter. Mean age at the time of diagnosis was 64.3 years. The most common symptoms were hematuria, flank pain and loss of weight. The diagnosis was established by intravenous pyelography and retrograde ureteropyelography. Ureteral carcinomas were operated with local resection of the ureter, while carcinomas of the renal pelvis were treated with a nephroureterectomia. Most tumours were highly malignant. Four tumours were non-invasive and, in retrospect, could have been treated with a local resection only. Only 35% of patients with urothelial carcinoma in the upper urinary tract are alive five years after diagnosis. PMID- 2309207 TI - [Jejunal diverticulitis]. AB - A patient with a history of 15 years of abdominal discomfort got acute localized peritonitis due to an inflamed jejunal diverticulum. The condition was successfully treated by resection of the diverticulum. PMID- 2309208 TI - [Myocardial 99mTc-pyrophosphate scintigraphy in acute heart infarct]. AB - 50 consecutive patients hospitalized because of suspected myocardial infarction were examined by 99mTc-pyrophosphate scintigraphy. The scans were interpreted blind by one of the authors. There were positive results in 17 of 21 patients with myocardial infarction (sensitivity 0.81). However, scintigraphy was also positive in 13 patients with no evidence of myocardial infarction as assessed by ECG and enzyme criteria (specificity 0.55). We conclude that, in our hospital, 99mTc-pyrophosphate myocardial scintigraphy did not contribute valuable information to the routine diagnosis of myocardial infarction. PMID- 2309209 TI - [Cardiogenic cause of cerebral embolism]. AB - Cerebral insults of cardiac origin are often of great functional importance. The most common cause is atrial fibrillation. Other sources of cerebral embolies, even if rare, such as cardiac tumors, must not be ignored. Many of these patients present neurologic symptoms. The diagnosis is established on ecco-cardiography. Surgical management is the treatment of choice. We discuss a young patient with multiple cerebral insults and a papillary cardiac tumor. PMID- 2309210 TI - [Cerebral gigantism--Sotos' syndrome]. AB - A review of three children who attended a school for the mentally retarded shows that they have Sotos' syndrome. Sotos syndrome, or cerebral gigantism, was first described in 1964. This syndrome is characterized by rapid growth from 1-4 years of age, advanced osseous maturation, large size at birth, macrocephally and a high forehead. The head also grows fast from infancy to two years of age. The children have mild dilatation of lateral ventricles, large hands and feet. They also have dysmorphic features, such as hypertelorism, down slanting palpebral fissure, higharched palate, non progressive neurological disorder and variable degrees of mental retardation. The etiology is unknown, but autosomal recessive cases have been reported. Some cases have subsequently shown a fragile x chromosome. Typically, the final height of the children is normal. PMID- 2309211 TI - [Neonatal asphyxia in full-term infants]. AB - This study includes 57 children born at term with asphyxia and admitted to Children's Department, Rikshospitalet, during the period 1981-85. The mortality in this study was 14% which proves that asphyxia represents a serious illness in newborn infants. The results of this investigation confirm that Apgar score is not a very precise parameter and offers limited information when estimating prognosis after birth. 17% of the newborn infants suffered from neonatal seizures during their first day in the neonatal period, and this symptom appears to indicate a high risk of subsequent mortality and morbidity. Nearly 44% of the newborns needed mechanical ventilation. PMID- 2309212 TI - [Alcoholics Anonymous. A society which greatly helps alcoholics]. AB - Alcoholics Anonymous is a society of men and women who share their experience, strength and hope with each other in order to solve common problems and help others to recover from alcoholism. The only requirement for membership is a desire to stop drinking. There are no dues or fees for a AA membership. The organization is self-supporting through its own contributions from members. AA is not allied to any sect, denomination, politics, organization or institution. It does not wish to become involved in any controversy, nor endorse or oppose any cause. The primary purpose is to stay sober and help other alcoholics to achieve sobriety. (The AA Preamble). This often quoted introductory statement of AA sets out the primary purpose, the requirement for membership and the general operational policy of an organization that has just recently celebrated its 50th anniversary, and has enjoyed a hegemony in the field of treatment of alcoholism for several decades. AA members seem to achieve a higher rate of abstinence than persons treated professionally. PMID- 2309213 TI - [Al-Anon. A resource for families and friends of alcoholics]. AB - Al-Anon, which includes Alateen, is a worldwide organization with a membership of some half million men, women and young people. The programme provides an accessible community resource, helping anyone who is deeply affected by the family disease of alcoholism. Al-Anon has a very special part to play for families whose alcoholic members are achieving sobriety through the AA programme. Through participation in Al-Anon's programme, family members are able to obtain a recovering and growing experience parallel to that of the alcoholic. Al-Anon is also helpful for families where the alcoholic does not want to stop drinking. They, too, are surrounded by warmth, understanding, concern and support while recovering. Al-Anon came to Norway in 1960, and today there are 40 groups. PMID- 2309214 TI - [Continent urostomy using Kock's method]. AB - Urinary diversion via a continent ileal reservoir ad modum Kock was performed in eight patients. There was no operative mortality. Early complications necessitated reoperation in three patients, two patients were reoperated due to leakage from the uretero-enteric anastomosis and one patient because of postoperative acute acalculous cholecystitis. Late complications were seen in two patients who were reoperated because of stenosis in the uretero-enteric anastomosis. All patients had excellent functional results with continence without reflux to the upper urinary tract. PMID- 2309215 TI - [Percutaneous lung puncture]. PMID- 2309216 TI - [Do calcium antagonists protect the heart?]. AB - There are several well-documented mechanisms by which calcium antagonists might reduce the size of an infarct and the complications that may result from it. They can improve flow, reduce demand, prevent calcium-induced damage and have an antiarrhythmic effect. In a large number of animal studies calcium antagonists have been shown to be cardioprotective, and some clinical trials have yielded encouraging results. These trials must be interpreted with some caution, however, since the relationship between various measures of infarct size, such as ECG changes and enzyme release, the amount of myocardial damage and the prognosis, may not be close. Furthermore, some trials yielded a negative result and further data are needed, based on large-scale double-blind controlled trials. Nevertheless, taken overall, the evidence suggests that calcium antagonists may play a cardio-protective role, and interest in this subject is certain to continue, and will probably increase. PMID- 2309217 TI - [Urinary incontinence and health insurance]. AB - We interviewed 187 women and 150 men with urinary incontinence. The majority of the patients had consulted their doctor about the problem (women 55%, men 83%), but had received inadequate information about the compensation provided under the National Insurance Act. Our findings suggest that the system of compensation provided for by the Act is by no means fully exploited. We review the provisions in the National Insurance Act which refer to urinary incontinence. PMID- 2309218 TI - [Are prosecuted parents allowed the benefit of the doubt in cases of child abuse?]. AB - The justified campaign against child abuse has unfortunately had a side effect. It has ruined the lives of some innocent parents of children with undiagnosed osteogenesis imperfecta. For 15 years, Colin Paterson and co-workers have studied a large number of patients with type IV of osteogenesis imperfecta, and have found that more than 50 per cent of them have normal radiographs of the bones at the time of the first fracture. Paterson and co-workers have also found that fractures of the ribs and skull are by no means uncommon in osteogenesis imperfecta type IV. These important observations should help, in the future, to prevent prosecution of innocent parents of children with osteogenesis imperfecta type IV, provided that the observations are not overlooked by pediatricians. PMID- 2309219 TI - [A shortage of organs for transplantation]. PMID- 2309220 TI - [More than genes--but less than a man?]. PMID- 2309221 TI - [Accidental hypothermia]. PMID- 2309222 TI - Trauma metabolism and the heart: studies of heart and leg amino acid flux after cardiac surgery. AB - Flux of plasma amino acids was measured across the heart and the leg (reflecting mainly skeletal muscle) in 18 patients 1 hour after completion of aorto-coronary bypass surgery. There was a net loss of amino acids from the leg (-324.9 +/- 39 nmol/min/100 ml tissue) while amino acid flux across the heart was not statistically different from zero. There were however positive intertissue correlations between leg and myocardial flux of tyrosine and most other amino acids, suggesting that protein metabolism of both tissues were affected in the same catabolic direction by the trauma response. Alanine and glutamine accounted for 50% of the amino acid release from the leg, which is in accordance with observations in association with other types of trauma. Alanine and glutamine also dominated amino acid release from the heart. Glutamate and aspartate were taken up by both tissues. The principal difference between the tissues was a myocardial uptake of leucine and isoleucine, in contrast to a leg release. PMID- 2309223 TI - Myocardial protective effects of lidoflazine during ischemia and reperfusion. AB - The myocardial protective effect of intravenous (i.v.) lidoflazine with potassium cardioplegia and hypothermia (28 degrees C) was investigated in 21 greyhounds. Animals were injected a single dose of cardioplegia (30 ml/kg body weight) and subjected to 120 minutes of ischaemia and 60 minutes of reperfusion. Ten dogs served as controls (Group C) and 11 dogs received i.v. lidoflazine (1.25 mg/kg b.w.) (Group L). Myocardial drill biopsies for the adenosine triphosphate (ATP) and the creatine phosphate (CP) levels were obtained. Hemodynamic measurements were made at intervals. In Group C, no dog could be weaned from bypass, whereas all 11 dogs in Group L came off bypass and maintained their circulation for 15 minutes. After a 120 minute ischemic period, the ATP and CP contents diminished significantly in both groups. Following reperfusion, the ATP level was 28% of the control level in Group C (p less than 0.005) and 38% in Group L (p less than 0.01). The CP levels showed an overshoot in both groups. There was no significant difference between the groups. In Group L animals, cardiac output (CO) and mean aortic pressure (MAP) were significantly reduced after bypass; from 5 +/- 1/min to 3.2 +/- 1, from 156 +/- 26 mmHg to 82 +/- 11 mmHg respectively (p less than 0.005). Left ventricular minute work (LVMW) also deteriorated markedly from 9.7 +/- 2 kg-m to 3.2 +/- 1 (p less than 0.005). The use of lidoflazine achieved considerable protection in terms of survival, but did not prevent the severe loss of high-energy phosphates in this experimental model. PMID- 2309225 TI - Uncommon type of mitral insufficiency caused by perivalvular communication between left ventricle and left atrium. AB - This case report describes a patient with an uncommon type of mitral incompetence caused by a perivalvular communication between the left ventricle (LV) and the left atrium (LA) masked by a considerable fibrotic subvalvular aortic stenosis, endocarditis and congestive heart failure (CHF). A 64 year old farmer with a history of a systolic murmur since childhood complaining of increasing fatigue and dyspnoea, temperature over 39 degrees C, and signs of CHF was admitted and transferred to a cardiological unit. Invasive examination and continuing clinical deterioration caused urgent transfer for surgery under suspicion of a decompensated hypertrophic obstructive cardiomyopathy. Clinical investigation revealed a decompensated subvalvular aortic stenosis and a mild mitral insufficiency. At surgery the advanced fibrotic subvalvular stenosis was resected. After coming off bypass severe mitral insufficiency was detected by intraoperative analysis of the simultaneous intracavitary-pressure tracings. A midsystolic maximum of a high V-wave of the LA-pressure tracing was suggestive of an unusual reason of the mitral insufficiency. Reexploration indicated a perivalvular broad communication from the LA groove to the LV with an otherwise normal mitral valve. The communication was closed using buttressed mattress sutures. This uncommon type of mitral incompetence via a perivalvular LA-LV communication was probably caused by endocarditis and an intramyocardial abscess in the LA-wall which subendocardially led to LV-LA communication. PMID- 2309224 TI - Coronary artery fistula as source of pulmonary circulation in pulmonary atresia with ventricular septal defect. AB - Four patients are described with pulmonary atresia and ventricular septal defect, in whom the pulmonary circulation was dependent on a fistula from the left coronary artery to the pulmonary artery. The issue in this complex anomaly is complete preoperative diagnosis, including anatomic information on the coronary artery fistula and the pulmonary vasculature. This was achieved in the last 2 patients. In the last patient echocardiography turned out to be an important diagnostic tool in this rare anomaly and facilitated selective angiocardiography. All 4 patients were successfully operated by closing the fistula, closing other aortopulmonary connections and inserting a valved conduit between right ventricle and pulmonary artery. The ventricular septal defect was closed in 3 patients with a patch. In the setting of an already existing pulmonary hypertension and a possibly inadequate pulmonary arterial system at surgery, a perforated patch was inserted in the ventricular septal defect of the remaining patient. PMID- 2309226 TI - Delayed surgical removal of a guide-wire fragment following coronary angioplasty. AB - Guide-wire fragments retained in the coronary artery system after PTCA are removed either immediately by means of catheter techniques or by urgent operation. We report on a case of a fractured guide wire which was left in a side branch of the right posterior descending coronary artery for 18 months due to the absence of any adverse effect. The small fragment was removed during an elective aorto-coronary bypass procedure. PMID- 2309228 TI - Tracheal stenosis caused by congenital vascular ring anomaly misinterpreted as asthma for 45 years. AB - Dyspnoeic conditions simulating asthma are not uncommon in adult and paediatric practice. Vascular ring anomalies in particular may be misdiagnosed, resulting in unnecessary delay before corrective surgery. We report a rare case of symptomatic double aortic arch in an adult which emphasises the above points. PMID- 2309227 TI - Intrapleural bupivacaine for early post-thoracotomy analgesia--comparison with bupivacaine intercostal block and cryofreezing. AB - 54 patients who had posterolateral thoracotomy were prospectively studied to compare the efficacy of intrapleural bupivacaine with that of bupivacaine intercostal block and cryofreezing. Patients were randomized into three groups. The intrapleural catheter group included 16 patients who had intermittent intrapleural instillation of 20 ml of 0.25% bupivacaine for forty-eight hours postoperatively. The second group included sixteen patients who were given perioperative bupivacaine intercostal block. The third group included fifteen patients treated by cryofreezing of the intercostal nerves. Visual analogue four hourly pain score was compared between the three groups during the first forty eight hours postoperatively. The analgesic requirements during the first postoperative week were also assessed. There was no significant difference between the three groups in the average pain score (3.61 +/- 1.37, 3.54 +/- 1.15, and 3.33 +/- 1.47 respectively). During the first forty-eight hours postoperatively, the percentage of patients who required papaveretum in the intrapleural catheter group (56.3%) was significantly less than that in the other two groups (both 100%). The average papaveretum requirement (mg per patient) in the intrapleural catheter group (27.33 +/- 25.27) was significantly less than that in the second group (52.66 +/- 26.85) but the difference was not statistically significant from that in the third group (37.66 +/- 20.95). No complications related to the use of the intrapleural catheter or to bupivacaine toxicity were encountered. In conclusion, the technique of intermittent intrapleural bupivacaine is safe and comparable in efficacy to bupivacaine intercostal block and cryofreezing. Narcotic requirements may be reduced when this technique is used. PMID- 2309229 TI - The hydatid cyst of the lung in children and results of surgical treatment. AB - Between 1976 and 1986 one hundred and ten children with pulmonary hydatid disease were treated surgically. Sixty five of the patients were males and 45 were females. We diagnosed hydatid cyst in 36 cases submitted in our clinic with hemoptysis. Thirty of the patients had cough, 16 had chest pain and dyspnea, 12 had purulent sputum and 8 cases had fever and anaphylactic phenomena. In most of the patients hydatid cysts were localised in the right lung. However, they had affinity for the lower lobes of both lungs, rather than the upper lobes. The radiological examination was found to be the most reliable diagnostic method. In the majority of our cases we performed thoracotomy + cystotomy + capitonnage, while in some cases we performed resection, like cystectomy, wedge resection and lobectomy. We did not encounter any serious operative and postoperative complications, except for one pleural empyema and a single case of mortality. PMID- 2309230 TI - Vascular injuries and amputation following limb fractures. AB - Sixty-seven cases treated for peripheral vascular injuries associated with fractures between the years of 1977 and 1988 in the Department of Thoracic and Cardiovascular Surgery of the Dicle University, Faculty of Medicine, were reviewed retrospectively. The cause of injury was blunt trauma in 37 cases (55%) and penetrating wounds in the others, 29 gunshot injuries and one case with a stab wound. The maintenance of vessel continuity was aimed at in all patients. The ratio of limb amputation was 13% in patients operated upon within the first 8 hours after the injury. The same ratio was 39% in cases where the surgical intervention was delayed beyond 8 hours. PMID- 2309231 TI - Haemodynamic effect of supraaortic ridge enhancement on the closure mechanism of the aortic valve and its implications in aortic valve repair. AB - The presence of the sinus of valsalva plays an essential part in the closing mechanism of the aortic valve. High-energy vortices are initiated at the upper limit of each sinus or supraaortic crest, and last during the whole valve closing time. An attempt was made to prove this hypothesis in vivo by intermittent augmentation of each supraaortic ridge. In a series of five dogs without cardiopulmonary bypass, pledgeted sutures were placed at the level of each crest and passed through tourniquets. In a series of three sheep, similar sutures were placed under direct vision with cardiopulmonary bypass. The supraaortic crests were augmented or maintained normal by tightening or loosening the tourniquets repeatedly. Simultaneous aortic and ventricular pressures and 2D- and M-mode echocardiography were recorded. In the dog series the results were unpredictable due to variability in the supraaortic crest enhancement because the sutures did not correspond to the anatomical crest. In the sheep series the sutures were correctly placed and M-mode echocardiography demonstrated a significant (p less than 0.01) shortening in systolic time. These results suggest the use of enhancement of the supraaortic crest as an adjunct technique in aortic valve repair. PMID- 2309232 TI - Effect of lead on the activity of erythrocyte porphobilinogen deaminase in vivo and in vitro. AB - The effect of lead on the activity of erythrocyte porphobilinogen deaminase (PBGD) in vivo and in vitro was investigated using blood specimens obtained from controls and lead-exposed workers. When lead nitrate was added to the incubation mixture at a final concentration of 10(-4) M, 83% inhibition of erythrocyte PBGD activity was found. However, in workers occupationally exposed to lead, no inhibition of erythrocyte PBGD activity was detected. This finding indicates that the erythrocyte PBGD test is not useful for evaluating exposure to lead in workers. In addition, the in vitro study confirmed that mercuric chloride strongly inhibits erythrocyte PBGD activity. PMID- 2309233 TI - In vitro cyto- and genotoxicity of organomercurials to cells in culture. AB - The sequence of cytotoxic effects for a series of mercury compounds to the BG/F epithelioid cells derived from fin tissue of bluegill sunfish was phenyl mercuric chloride greater than methyl mercuric chloride greater than ethyl mercuric chloride much greater than mercuric chloride. This sequence of in vitro cytotoxicity was similar to that observed in a 48-h LC50 in vivo acute toxicity assay with rainbow trout. Using induction of micronuclei as an indicator of genetic damage, the organomercurials, but not mercuric chloride, were noted to be clastogenic to the BG/F cells. PMID- 2309234 TI - Effect of ethanol on fatal carbon monoxide poisoning in awake mice [correction of rats]. AB - The effect of ethanol on fatal carbon monoxide (CO) poisoning was investigated in mice injected intraperitoneally with ethanol. Ethanol (1.5 and 3.0 g/kg) was injected 15 min prior to exposure to gas containing 6.6% CO. The survival period was significantly lengthened with ethanol in proportion to the doses injected, although the carboxyhemoglobin (CO-Hb) saturation level in postmortem blood was almost the same in all groups. On the other hand, the CO-Hb level in the blood of mice injected with ethanol was significantly lower than that of control mice during the early exposure period when all mice were still alive. Our results showed that the acute ethanol injection did not influence the CO-Hb saturation level in blood at death, but did affect the duration of survival, probably because of ethanol's ability to decrease blood flow and CO intake. PMID- 2309235 TI - Absorption of methylmercury compounds from rat intestine. AB - Intestinal absorption of methylmercury complexed with non-protein sulfhydryl compounds (NPSHs) as occurs in bile was studied by means of direct injection of mercury compounds into ligated intestinal segments of rats. The extent of absorption of methylmercury-cysteinylglycine (MM-CysGly) was similar to that of methylmercury-cysteine (MM-Cys) and 1.5 times larger than that of methylmercury glutathione (MM-GSH). This results suggested that MM-CysGly, which is recognized as a major component of methylmercury in rat bile, can be easily reabsorbed from the intestine. These results indicate that not only MM-GSH and MM-Cys but also MM CysGly may play important roles in the intestinal reabsorption of methylmercury during its enterohepatic circulation. When the ligated intestine was pretreated with probenecid and acivicin, the intestinal absorption of MM-GSH was depressed much more than in the case of treatment with acivicin alone. This indicates the possibility that there are at least two systems for intestinal transport of MM GSH, i.e. gamma-glutamyltranspeptidase (GGT)-dependent and -independent systems. PMID- 2309236 TI - Lack of covalent binding to DNA of di-n-octyltin dichloride (DOTC) in vivo and in vitro. AB - [14C]Di-n-octyltin dichloride ([14C]DOTC) was administered by oral gavage to male and female rats. After 96 h hepatic and thymic DNA was isolated. All DNA fractions were radioactive, but analysis of DNA hydrolysates by HPLC revealed that the radioactivity was incorporated via biosynthesis and was not due to adduct formation. The limit of detection for adduct formation, expressed in units of the covalent binding index (CBI = mumol chemical bound per mol nucleotides/mmol chemical applied per kg body wt.) was approximately 0.2 for liver DNA and about 0.7 for thymus DNA. This maximum possible DNA-binding ability is about 30,000 times lower than the corresponding value for the strong carcinogen, aflatoxin B1. In addition, [14C]DOTC did not bind covalently to calf thymus DNA in the presence or absence of rat liver S9 or to DNA of V79 Chinese hamster cells. This study therefore gives no indication for genotoxic activity of DOTC mediated by DNA binding. PMID- 2309237 TI - Evaluation of the teratogenic potential of the dopamine agonist bromocriptine in rats. AB - Single subcutaneous injections of bromocryptine (BCR; 2 mg/kg) to rats on days 5, 7 or 10 of gestation caused a lowering of the serum prolactin (PRL) concentration and, on days up to and including day 8 of gestation, abortion of entire litters. Coincident with the end of the PRL-dependent phase of gestation (approximately day 9), BCR was no longer abortifacient, allowing higher doses of the drug to be administered from this time without the risk of abortion. Treatment at 50 or 100 mg/kg from day 10 to 16 of pregnancy, despite affecting the dams (increased water consumption), had no adverse effects on pregnancy or fetal development. PMID- 2309238 TI - Dose-dependent kinetics of inhaled methylethylketone in man. AB - Physiologically based stimulation of earlier human inhalation exposure to methylethylketone (MEK) at a concentration of 200 ppm for 4 h suggested that the kinetics were dose-dependent. Two male volunteers were therefore exposed to MEK for 4 h at 3 exposure concentrations: 25, 200 and 400 ppm. Blood MEK concentrations were monitored during and after exposure. The results showed clearly that the kinetics of MEK were dose-dependent at higher exposure concentrations. Simulated exposure to MEK for 8 h suggests that saturation kinetics are reached at an exposure concentration of 50-100 ppm, depending on the physical work load. PMID- 2309239 TI - The effect of cadmium on the composition and metabolism of hepatic fatty acids in zinc-adequate and zinc-deficient rats. AB - Exposure to cadmium (Cd) caused changes in the fatty acid composition of phospholipids, such as increases in levels of saturated and (n-6) fatty acids and decreases in levels of (n-9) fatty acids, in the liver phospholipids of rats fed a fat-free diet. These changes were similar to those caused by dietary zinc deficiency. The changes in fatty acid composition after administration of Cd were greater in zinc-deficient (ZD) rats than zinc-adequate (ZA) rats. When [14C]18:0 was injected intravenously in order to examine the metabolism of (n-9) fatty acids, a decrease in the rate of conversion of [14C]18:0 to [14C]18:1 was observed in liver phospholipids after treatment of ZD rats with Cd. These results suggested that Cd can affect the metabolism of fatty acids in relation to zinc status and, in particular, causes a reduction in the activity of delta 9 desaturase which converts 18:0 to 18:1. PMID- 2309240 TI - Detection and quantitative determination of 3-nitropropionic acid in bovine urine. AB - The separation and determination of 3-nitropropionic acid (NPA) in bovine urine by reverse-phase HPLC is described. The method utilizes a rapid ethyl acetate extraction and this clean-up step also improves the chromatographic resolution of NPA in bovine plasma. A simple colorimetric method is also developed for the rapid detection and estimation of NPA in urine and the data indicate that it is in good agreement with the HPLC procedure. PMID- 2309241 TI - Plasma electrolyte changes after ingestion of bile extract of the grass carp (Ctenopharyngodon idellus) in rats. AB - Some Chinese people believe that eating the gallbladder of the grass carp (Ctenopharyngodon idellus) may improve their visual acuity. However, ingestion of grass-carp bile, in severe cases, may kill human beings and experimental animals. The cause of death after eating grass-carp bile was studied in rats. The bile acid fraction was prepared from the n-hexane-insoluble and alcohol-soluble parts of grass-carp and hog bile. The bile extract (6 ml/kg, 15%) was administrated by gastric intubation to conscious female Long-Evans rats. Ingestion of grass-carp bile extract killed all the experimental rats in 2-8 h and was associated with a decrease in blood pressure and an increase in plasma potassium, hydrogen ions, blood urea nitrogen and hematocrit. However, rats that ingested hog bile or saline showed no significant changes in the measured parameters. If the rats were fed cholestyramine-treated grass-carp bile extract, they survived without significant change in the measured parameters. This report demonstrates that a drastic increase in plasma potassium and hydrogen ions probably caused the death of the rats, and also shows that bile acid (alcohol) in grass-carp bile is related to the toxicity. PMID- 2309242 TI - Protection by exogenous glutathione against hypoxic and cyanide-induced damage to isolated perfused rat livers. AB - In experiments with isolated perfused livers from fasted rats, addition of 2 mmol/l glutathione (GSH) to the perfusion medium protected against hepatic damage induced by cyanide or hypoxia and reoxygenation as evidenced by leakage of lactate dehydrogenase and hepatic calcium accumulation. In control experiments as well as in experiments with cyanide or hypoxia and reoxygenation, exogenous glutathione resulted in an augmentation of cellular glutathione content, indicating either direct uptake of GSH or stimulation of its intracellular synthesis. The protective effects of glutathione against hypoxic and cyanide induced hepatotoxicity substantiate the role of oxidative stress in both types of injury. PMID- 2309243 TI - Cisplatin nephrotoxicity in lead-pretreated rats: enzymatic and morphological studies. AB - Treatment of rats with cisplatin or with cisplatin after chronic pre-exposure to lead induced a decrease in cytochrome P-450, reduced glutathione (GSH), GSH-S transferase, reductase and peroxidase activities, and an increase in N-glucuronyl transferase, lipid peroxidation and oxidized glutathione (GSSG). On histological examination, rats treated by lead or cisplatin and by lead + cisplatin revealed significant proximal tubular lesions which varied from minimal changes to severe necrosis. Lead toxicity was characterized by irregularity and thickening of glomerular basement membranes, and by tubular mitochondrial alterations associated with the presence of intranuclear inclusions. Cisplatin injury showed more extensive lesions with cellular disorganization. Except for an increase in N glucuronyl transferase activity, lead did not exert any significant effect on these biochemical and histological parameters and did not significantly modify the deleterious effects of further therapy by cisplatin. PMID- 2309244 TI - Embryotoxic evaluation of bis(tri-n-butyltin)oxide (TBTO) in mice. AB - Pregnant mice were treated on days 6-15 of gestation with 5, 20 and 40 mg/kg/d bis(tri-n-butyltin)oxide (TBTO), and sacrificed on gestational day 17. At the highest dose TBTO caused a significant reduction of maternal body weight gain and also proved to be highly embryotoxic. Necropsy showed a dose-related decrease in spleen weight while a dose-dependent increase in placental weight was observed. PMID- 2309245 TI - Effect of methoxyethanol, cyclophosphamide and cadmium on metallothionein levels during prenatal development in the mouse. AB - Three known teratogenic agents--methoxyethanol (ME), cyclophosphamide (CP) and cadmium (Cd)--are possible inducers of metallothionein (MT) in the embryo and/or in the fetus. Their effect on the MT levels of forelimbs, brain and liver during prenatal development and in dam's liver was studied in the mouse to elucidate whether MT could be used as an early biochemical indicator of teratogenicity. Pregnant mice were injected with 2 doses of each teratogen at different days of the middle gestational phase and their embryos and fetuses were obtained thereafter. Quantitative estimation of MT in the S9 from homogenates of the embryo/fetal tissues and organs and maternal liver showed major alterations in the dam's hepatic MT content but only small changes in prenatal MT levels. These results do not support MT as an early indicator of teratogenicity. However, a causal relationship between the maternal MT changes induced by the tested agents and their teratogenic effect could be possible. PMID- 2309246 TI - Relative distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in human hepatic and adipose tissues. AB - Paired human hepatic and adipose tissues from 26 people were assayed for 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). On a whole tissue weight basis, TCDD concentration in the liver was about one-tenth that in the adipose tissue. When expressed in total tissue lipid basis, the TCDD concentrations in the liver and adipose tissue were about equal. At low levels of exposure, presumably below those necessary to cause hepatic enzyme induction, TCDD appeared to be partitioning into the human liver predominantly on the basis of its lipid solubility in that tissue store. The partitioning behavior of TCDD in the livers of humans exposed to higher levels of TCDD is currently unclear. PMID- 2309247 TI - Cocaine toxicity in cultured rat hepatocytes. AB - Cocaine hydrochloride was added to primary cultures of hepatocytes isolated from naive and phenobarbital-induced (80 mg/kg i.p. for 3 d) Sprague-Dawley rats. Cocaine was cytotoxic, as measured by lactate dehydrogenase release, to cells from naive rats in concentrations of 1 mM or greater. Phenobarbital induction greatly increased the cytotoxic potency of cocaine in vitro, with nearly complete loss of cell viability at cocaine concentrations in culture as low as 0.01 mM. The addition of 10 microM SK&F-525-A to the cultures blocked cocaine cytotoxicity in cells from both naive and phenobarbital-induced rats. These results suggest that the metabolic pathways leading to cocaine hepatotoxicity identified in the mouse also exist in the rat hepatocyte. PMID- 2309248 TI - Susceptibility to cyclophosphamide and thalidomide of fetal rat limb buds grafted in athymic (nude) mice. AB - Limb buds of day-14 rat fetuses were cut into pieces and transplanted into athymic (nude) mice. On the 7th and 9th days after grafting, the host nude mice were given cyclophosphamide intraperitoneally (10-120 mg/kg) or thalidomide orally (30-240 mg/kg). On the 20th day, the grafted tissue was examined macroscopically and histiologically. The grafts maintained in vehicle-treated nude mice showed considerable growth and tissue differentiation similar to in vivo. Growth and histogenesis of the grafts were significantly inhibited by treatment with cyclophosphamide (greater than or equal to 20 mg/kg). There was no indication that treatment with thalidomide (less than or equal to 240 mg/kg) adversely affects the development of grafted limbs. Thus, the susceptibility of transplanted rat limb buds to these two human teratogens was identical to the susceptibility of living rat fetuses. The heterotransplantation method of embryonic tissues may be of potential use for the study of teratogenic mechanisms and for the screening of human teratogens. PMID- 2309249 TI - Transient hypothermia and hyperphagia induced by selenium and tellurium compounds in mice. AB - The effects of sublethal doses of selenite, selenate, selenocystine (Se-Cys) and selenomethionine (Se-Met) as well as of tellurite on body temperature and feeding behavior were examined in male ICR mice. Ten or 30 mumol/kg of chemicals were injected subcutaneously and body temperature was measured up to 4 h. In a separate experiment, the gastric content was weighted 4 h after injection. All chemicals except Se-Met induced both hypothermia and hyperphagia, suggesting that: (a) these two effects are related to each other; (b) among the chemicals tested, Se-Cys appears to be the most potent hypothermia inducer; (c) Se-Met is unique in that it has neither effect. PMID- 2309250 TI - An assessment of the genotoxicity of vanadium. AB - The activities of vanadium oxide (V2O3), vanadyl sulfate (VOSO4) and ammonium metavanadate (NH4VO3) in inducing sister chromatid exchange (SCE) and chromosomal aberrations (CAb) were assayed in Chinese hamster ovary cells. The toxic concentrations (TC50) for these compounds were found to be 25, 23 and 16 micrograms elemental vanadium/ml, respectively. At does 1/50-1/4 TC50, vanadium compounds were able to induce significant increases (P less than 0.01) in the SCE frequency with or without the addition of rat hepatic S9 mix. These compounds also induced CAb in the cells at doses closely equivalent to the TC50. PMID- 2309251 TI - A physiological pharmacokinetic model describing the disposition of lead in the absence and presence of L-ascorbic acid in rats. AB - The influence of L-ascorbic acid (As-Ac) on the multiple-tissue disposition of lead has been evaluated. Lead concentrations in femur, liver, kidney and plasma of rats were monitored over a 120h period after its intravenous bolus administration (1.0 mg/kg) in the absence and presence of As-Ac at steady state. The observed lead concentration-time data in different tissues of the rats, in the absence and presence of As-Ac, have been simulated using a physiological pharmacokinetic modelling technique. In both cases, the predicted lead concentrations in various tissues were in adequate agreement with the observed data. The model developed in the present investigation supports the previous finding that As-Ac may be useful as a prophylactic agent for lead poisoning. PMID- 2309252 TI - The induction of dominant lethal mutations upon chronic administration of khat (Catha edulis) in albino mice. AB - The mutagenicity of a methanolic extract of khat has been evaluated on male germ cells using the dominant lethal test in albino mice. An aqueous solution of khat extract was administered orally in doses of 50, 100 and 200 mg/kg body wt., respectively, to 3 different groups of male mice for a period of 6 weeks. At the end of treatment each male mouse was allowed to mate with 2 different groups of 3 females each, on 2 consecutive weeks. These females were necropsied on the 13th day of their presumptive mating, and the number of implants in each female and the ratio of live and dead embryos were determined. The results of this study showed that the treatment of male mice over a period of 6 weeks produced a dose dependent reduction in the rate of fertility in the first week after mating, which was irreversible in the second week at the highest dose (200 mg/kg). Khat extract also induced post-implantation loss during the first week following treatment. However, a comparison of the results of the first and second weeks showed a reversible pattern of dominant lethality. PMID- 2309253 TI - Microbiologic transformation of progesterone by Curvularia clavata Jain. AB - Progesterone was transformed microbiologically by the fungal strain Curvularia clavata Jain. Progesterone (I) was added as substrate when the microorganism reached its exponential growth phase. Three substances were isolated after the fermentation: a non-steroidal substance, radicinin (II), which has been established to be a metabolic product of the fungus and acts as a phytotoxin, and two steroidal substances which resulted from fungal enzymatic action on the progesterone molecule. The structure of each microbial metabolite was elucidated by 1H-nuclear magnetic resonance, mass spectrometry, and infrared and UV analyses, and the yields were determined by high-pressure liquid chromatography. The progesterone metabolites were characterized as 7 alpha,14 alpha dihydroxypregn-4-ene-3,20-dione (III) and 11 beta, 14 alpha-dihydroxypregn-4-ene 3,20-dione (IV). Evidence for the structure of these steroidal products came from derivatives resulting from acetylation and dehydration. PMID- 2309254 TI - Effects of exogenous thyroxine on C-2 and C-16 alpha hydroxylations of estradiol in humans. AB - Thyroid dysfunction in humans is known to alter the excretory pattern of estrogen metabolites, suggesting that thyroid hormone directly influences the oxidative metabolism of estradiol. We examined the extent to which a brief period of hyperthyroidism specifically affected estradiol hydroxylation at C-2 and C-16 alpha, the two primary and competing sites of estrogen oxidation, using an in vivo radiometric assay in healthy male volunteers. Hydroxylation at C-2 was increased by a 2-week course of thyroxine (4.3 micrograms/kg/d) from 29.9% +/- 2.6% to 35.9% +/- 3.1% (P = 0.04), while 16 alpha-hydroxylation was unchanged (10.3% +/- 0.8% versus 9.3% +/- 0.5%). The greater extent of oxidation at C-2 was evidenced by a twofold increase in the urinary excretion of 2-hydroxyestrone (2.88 +/- 0.32 versus 5.30 +/- 0.85 micrograms/g creatinine), while the excreted products of 16 alpha-hydroxylation were unchanged. At the same time, significant reductions in total cholesterol (173.8 +/- 7.9 versus 139.4 +/- 8.9 mg/dl), low density lipoprotein cholesterol (110.0 +/- 5.3 versus 83.8 +/- 7.7 mg/dl), and apolipoprotein B (68.2 +/- 3.3 versus 53.1 +/- 3.6 mg/dl) were observed. Serum levels of estrone, estradiol, sex hormone-binding globulin, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, and apolipoprotein A-I were not significantly affected. This study adds to the growing evidence that catechol estrogen production in humans is more readily regulated than 16 alpha-hydroxylation, which is relatively refractory to treatment. PMID- 2309255 TI - Influence of rete testis fluid deprivation on the kinetic parameters of goat epididymal 5 alpha-reductase. AB - A surgical technique to cannulate the rete testis of the goat was utilized to examine the effects of rete testis fluid (RTF) deprivation on the enzymatic activity of epididymal 5 alpha-reductase. Kinetic techniques were used to determine whether the regional enzymatic effect of RTF deprivation is to decrease the apparent number of 5 alpha-reductase active sites or the catalytic activity of each active site within the epididymal epithelium. Paired comparisons of (Vmax)app and (Km)app values between control and RTF-deprived epididymides indicated that RTF deprivation affected the value of (Vmax)app with no apparent change in the values of (Km)app in caput, corpus, and cauda epididymal regions. We conclude that RTF deprivation in the goat epididymis for 7 days results in a decreased number of apparent 5 alpha-reductase active sites within the epididymal epithelium. PMID- 2309256 TI - Long-acting contraceptive agents: testosterone esters of unsaturated acids. AB - The synthesis of 13 new esters of testosterone is described, with the esterifying acids bearing acetylenic, olefinic, or polyunsaturated functions in the chain, for evaluation as long-acting androgens. PMID- 2309257 TI - Effects of serum proteins on estrogen action in the perfused rat liver. AB - To determine the effects of serum proteins on the biologic activity of estrogens, we perfused isolated livers from ovariectomized female rats with oxygenated Krebs Henseleit-bicarbonate buffer (KHBB), with and without 4% human serum albumin (4% HSA), with and without added estrogens, or with charcoal-stripped human serum (CSHS) with and without added estradiol. At the end of the perfusions, the cytosolic and nuclear estrogen receptors were measured by an exchange assay. When added to KHBB, estradiol 10(-9) or 10(-8) M or estrone 10(-8) M did not cause any significant increase in the percent of receptors measured in the nucleus. When the livers were perfused with KHBB containing 4% HSA and estradiol 10(-9) to 10( 7) M or estrone 10(-8) M, there was an increase in nuclear receptors. Perfusion with estradiol 10(-8) M in CSHS resulted in significantly less receptor in the nucleus than after estradiol in KHBB plus 4% HSA. We conclude that the presence of 4% HSA in the perfusion medium increases the biologic activity of estradiol and estrone on the isolated rat liver, and this increase is inhibited in the presence of sex hormone-binding globulin. The exact mechanism by which HSA increases the biologic activity is uncertain, but may be due in part to better diffusion of estrogen through the liver. PMID- 2309259 TI - The decade of the brain: challenge and opportunities in stroke research. PMID- 2309258 TI - Synthesis of 19-hydroxy-[7-2H2]androstenedione for human metabolism studies. AB - 19-Hydroxyandrostenedione (19-OHA), highly labeled with deuterium at position 7, was synthesized from unlabeled androstenediol diacetate. The deuterium labels were introduced into the 7-keto compound with dichloroaluminum deuteride to obtain [7-2H2]androstenediol. The labeled androstenediol diacetate was converted to the labeled 19-OHA by a five-step sequence without appreciable loss of deuterium. The labeled 19-OHA is useful as an internal standard for gas chromatography-mass spectroscopy analysis of the endogenous levels and as a tracer for in vivo metabolic studies. PMID- 2309260 TI - Are hypertension or cardiac embolism likely causes of lacunar infarction? AB - We tested the hypothesis that hypertension is more common and cardiac embolism less common in patients with lacunar infarction than in patients with other types of cerebral infarction. We studied risk factor profiles in a series of 102 consecutive patients with a lacunar infarct and 202 consecutive patients with a carotid artery-distribution infarct involving the cortex registered in the Oxfordshire Community Stroke Project, a community-based study of first-ever stroke. The two groups did not differ in the prevalence of prestroke hypertension (defined in a number of ways) or in the prevalence of markers of sustained hypertension. The presence of atrial fibrillation and a history of myocardial infarction, particularly during the 6 weeks before the stroke, were significantly more common in the group with carotid-distribution infarcts involving the cortex. There was no significant difference in the prevalence of other accepted risk factors for ischemic stroke, including previous transient ischemic attack, cervical bruit, diabetes mellitus, peripheral vascular disease, or cigarette smoking. Our results suggest that hypertension is no more important in the development of lacunar infarction than it is in the development of other types of ischemic stroke that are presumed to be due to atherosclerotic thromboembolism in a major cerebral artery. Our data support the autopsy evidence that cardioembolic occlusion is an unusual cause of lacunar infarction. PMID- 2309261 TI - Stroke in young adults. AB - Strokes in young adults are uncommon and often a diagnostic challenge. A retrospective study of strokes due to intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction was undertaken. We reviewed the medical records of 113 young patients aged 15-45 years who were admitted to the Medical Center Hospital of Vermont with a diagnosis of stroke between 1982 and 1987. This group comprised 8.5% of patients of all ages admitted for stroke, 2.3 times the proportion observed in the National Survey of Stroke. Nontraumatic intracerebral hemorrhage was diagnosed in 46 young patients (41%); the main causes included aneurysms, arteriovenous malformations, hypertension, and tumors. Subarachnoid hemorrhage was found in 19 young patients (17%); the majority were due to aneurysms. The remaining 48 young patients (42%) had cerebral infarction, the majority due to cardiogenic emboli and premature atherosclerosis. Mitral valve prolapse, the use of oral contraceptives, alcohol drinking, and migraine were infrequent sole causes of cerebral infarction in the absence of other risk factors. The case-fatality rate for this group of young patients with stroke was 20.4% compared with 23.9% for the National Survey of Stroke. Young adults with stroke deserve an extensive but tailored evaluation, which should include angiography and echocardiography. PMID- 2309262 TI - Circadian variation in the frequency of ischemic stroke. AB - The frequency of myocardial infarction and sudden death is increased between 6 AM and noon. To determine whether the same is true for the onset of ischemic stroke, we studied 426 consecutive patients within 12 hours after the onset of their first hemispheric stroke. The frequency of onset of hemispheric stroke was significantly (p = 0.0001) higher from 6:01 AM to noon (56.1%) than from 12:01 PM to 6 PM (20.2%), from 6:01 PM to midnight (8.2%), and from 12:01 AM to 6 AM (15.5%). The identification of periods of high risk for vascular events may have important therapeutic implications, such as matching drug effects with vulnerability. PMID- 2309263 TI - Epidemilogy of stroke in the Poznan district of Poland. AB - The incidence of cerebrovascular disease was established in the Poznan district in Poland for 1985. Mortality from cerebrovascular disease during this year was compared with mortality during 1977. The autopsy material from the years 1925 to 1985 was analyzed to differentiate ischemic from hemorrhagic stroke. The incidence of stroke was 198.3 per 100,000 inhabitants greater than 20 years of age. Mortality from cerebrovascular disease decreased significantly in both males and females from 1977 to 1985. Analysis of the pattern of cerebrovascular disease in the autopsy material from 1925 to 1965 demonstrated an overwhelming percentage of hemorrhagic stroke. In the years that followed, an inversion was noticed in the ratio of ischemic to hemorrhagic stroke. It should be assumed that the growing efficacy of antihypertensive therapy largely explains the decreasing incidence of stroke-induced mortality. PMID- 2309264 TI - Deep cerebral infarcts in the People's Republic of China. AB - We reviewed computed tomograms and clinical characteristics for 1,124 consecutive stroke patients from Shanghai, People's Republic of China. While there were many similarities between lacunar syndromes in these patients and patients from Europe and the United States, several differences were noted. Deep cerebral infarcts identified by computed tomography were more common in patients from Shanghai and accounted for 27% of all ischemic infarcts. Small deep infarcts occurred more commonly in women from Shanghai (44%) than in women from the West. Deep cerebral infarcts in patients from Shanghai were larger than those usually seen in patients from the West. The mean infarct volume in patients from Shanghai was 2.4 ml, and 49% were giant lacunes (greater than 15 mm in maximal diameter). PMID- 2309265 TI - Wallerian degeneration of the pyramidal tract in capsular infarction studied by magnetic resonance imaging. AB - Using magnetic resonance imaging, we studied 24 patients with ischemic infarction of the internal capsule. Magnetic resonance imaging detected wallerian degeneration of the pyramidal tract below the capsular lesion in 11 patients (45.8%); all 11 had clinical evidence of pyramidal tract damage. In six additional patients magnetic resonance imaging findings, present only on axial slices, were considered to indicate possible wallerian degeneration. When motor deficit was associated with posterior limb lesions, magnetic resonance imaging detected wallerian degeneration of the pyramidal tract in 78.6% (11) of 14 patients. PMID- 2309266 TI - Noninvasive study of arterial hypertension and carotid atherosclerosis. AB - We noninvasively evaluated the prevalence and severity of atherosclerotic lesions of the internal carotid artery in 146 nonobese, nondiabetic hypertensive patients who were free of cardiovascular symptoms. We found internal carotid artery disease in 63 patients (43%), 26 (18%) with unilateral disease and the other 37 (25%) with bilateral disease. Disease severity was correlated with age but not duration of hypertension, cholesterol level, or current smoking habit. We also followed disease progression and clinical outcome with respect to cardiovascular events for 3 years in a subgroup of 95 unselected patients. In 20 of the 93 survivors (21.5%) we noted progression of the atherosclerotic lesions that was predicted by neither risk factors nor initial status of the internal carotid artery. New neurologic symptoms developed in four survivors (4%) and symptoms of cardiac ischemia in six (6%). No survivor who developed new cerebrovascular symptoms showed progression of carotid disease. These data provide useful elements for a rational approach to prevention of the atherosclerotic complications of hypertension. PMID- 2309267 TI - Neuropathologic consequences of internal carotid artery occlusion and hemorrhagic hypotension in baboons. AB - We studied eight anesthetized and physiologically monitored adult baboons (Papio cyanocephalus); four were subjected to hemorrhagic hypotension alone and four to hemorrhagic hypotension plus unilateral carotid artery occlusion. Cerebral blood flow was measured using xenon-133, the electroencephalogram was recorded using silver-silver chloride epidural electrodes, and histologic examination was carried out after perfusion-fixation. In the baboons subjected to hypotension alone (mean arterial blood pressure of 28 mm Hg) cerebral blood flow was 28.5 +/- 5.0 ml/100 g/min, whereas in the baboons subjected to hypotension plus unilateral carotid artery occlusion it was 21.8 +/- 1.8 ml/100 g/min at a mean arterial blood pressure of 27 mm Hg. There was no ischemic damage in the former group, but in the latter group there was necrosis in the arterial boundary zones of three baboons and in the distribution of the middle cerebral artery in one. We conclude that, when combined with hypotension, unilateral carotid artery occlusion may lead to hemodynamic ischemia accentuated in the arterial boundary zones of the ipsilateral cerebral hemisphere. PMID- 2309268 TI - Perivascular blood attenuates noradrenergic but not cholinergic effects on piglet pial arterioles. AB - We examined the chronic and acute effects of perivascular blood on cerebrovascular responses to norepinephrine and acetylcholine in 35 piglets. In the chronic experiment, fresh autologous blood (n = 15) or cerebrospinal fluid (n = 14, control) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to 4 days later, a closed cranial window was placed over the parietal cortex and baseline pial arteriolar responses and responses to topical application of the neurotransmitters norepinephrine (10(-6) and 10(-4) M) and acetylcholine (10(-4) M) were determined. We also sampled cerebrospinal fluid from under the window during baseline conditions and during application of the neurotransmitters, and we measured the concentrations of prostanoids (6-ketoprostaglandin F1 alpha, thromboxane B2, prostaglandin F2 alpha, and prostaglandin E2) via radioimmunoassay. Pial arterioles in the chronic control group (n = 13) constricted by 20 +/- 2% (mean +/- SEM) in response to 10(-4) M norepinephrine and by 28 +/- 2% in response to 10(-4) M acetylcholine. In the chronic blood group (n = 14), pial arterioles did not constrict significantly in response to 10(-4) M norepinephrine but constricted normally (23 +/- 4%) in response to 10( 4) M acetylcholine. In the acute experiment, six other piglets had blood placed on the brain surface for 30 minutes and then removed; pial arterioles constricted by 21 +/- 1% in response to 10(-4) M norepinephrine (n = 5) and by 28 +/- 4% in response to 10(-4) M acetylcholine (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309269 TI - Effect of hyperglycemia on neuronal changes in a rabbit model of focal cerebral ischemia. AB - In clinical medicine, cerebral ischemia is frequently due to a focal, rather than global, insult. The effect of hyperglycemia in focal cerebral ischemia is not well defined. We studied the effect of hyperglycemia on neuropathologic changes in a rabbit model of focal cerebral ischemia. Rabbits were randomized to receive saline (n = 12) or glucose (n = 12) infusions. The left anterior cerebral and left internal carotid arteries were clipped after the infusion began. After 6 hours of occlusion, the area of severe ischemic neuronal damage in the left neocortex and striatum on two standard sections of brain was calculated and expressed as a percentage of the total area of the left cortex or striatum. The mean +/- SEM cortical area of severe ischemic neuronal damage was 22.1 +/- 2.8% in the glucose-treated rabbits and 34.0 +/- 4.6% in the saline-treated rabbits (p less than 0.05). The cortical area of severe ischemic neuronal damage was inversely correlated with plasma glucose concentration at the time of arterial clipping (p less than 0.05). We conclude that hyperglycemia is associated with decreased histologic neuronal injury in this model of focal cerebral ischemia and may be protective when cerebral ischemia occurs from a focal insult. PMID- 2309270 TI - Endogenous platelet activating factor does not modulate blood flow and metabolism in normal rat brain. AB - Both platelet activating factor and eicosanoids participate in the cerebrovascular response to ischemia. Eicosanoids also modulate cerebrovascular tone under normal physiologic circumstances, but a similar role for platelet activating factor has not been investigated. Therefore, using 16 rats, we studied the effects of the platelet activating factor receptor blockers BN 52021 (10 mg/kg, n = 4 or 30 mg/kg, n = 2) and WEB 2086 (5 mg/kg, n = 6) on global cerebral blood flow and the cerebral metabolic rate for oxygen and compared them with the effect of indomethacin (10 mg/kg, n = 4). Neither antagonist altered cerebral blood flow (112 +/- 16 and 107 +/- 14 ml/100 g/min at baseline versus 108 +/- 16 and 105 +/- 18 ml/100 g/min after BN 52021 and WEB 2086, respectively). In contrast, indomethacin significantly (p less than 0.05) decreased cerebral blood flow from 106 +/- 8 to 69 +/- 4 ml/100 g/min. No treatment altered the cerebral metabolic rate for oxygen compared with baseline. These data suggest that in normal rat brain, concentrations of platelet activating factor, unlike those of eicosanoids, are subthreshold and do not modulate cerebral blood flow or the cerebral metabolic rate for oxygen. PMID- 2309271 TI - Chronic cerebral intracellular alkalosis following forebrain ischemic insult in rats. AB - We measured cerebral intracellular pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy during 1 week after forebrain ischemia or sham operation in eight and seven rats, respectively. Mean maximum pH was significantly higher (p less than 0.003) in the ischemic group than in the sham operated group (7.34 +/- 0.03 and 7.19 +/- 0.02, respectively). The difference between mean maximum pH and baseline pH (7.08 +/- 0.01 in each group) was significantly greater (p less than 0.02) in the ischemic group than in the sham operated group. In the ischemic group, alkalosis occurred primarily after 48-72 hours of recirculation. We speculate that brain tissue alkalosis occurring chronically after ischemia is associated with delayed ischemic neuronal death. PMID- 2309272 TI - Impairment of metabolic recovery with increasing periods of middle cerebral artery occlusion in rats. AB - We examined the consequences of reflow on metabolic recovery following increasing periods of focal ischemia. The middle cerebral artery of 21 Sprague-Dawley rats was occluded with a snare ligature for 1, 2, or 6 hours followed by 5, 4, or 0 hours of reflow, respectively (seven rats in each group). All animals were injected with neutral red for visual confirmation that the affected regions were reperfused. The brains were frozen in situ, and the concentrations of adenosine triphosphate, phosphocreatine, glycogen, and lactate were determined in those areas corresponding to the normally perfused medial ipsilateral cortex, the perifocal region, and the ischemic focus. Values for the 6 hours' occlusion with no reflow group served as a control to demonstrate restoration of metabolite concentrations. In both groups with reflow, the levels of high-energy phosphates were greater than control, but this effect of reflow was primarily significant for the group with 1 hour's occlusion (p less than 0.05). The levels of glycogen and lactate provided additional evidence that the extent of metabolite restoration was graded; following 2 hours of occlusion, metabolite recovery was compromised (p less than 0.05). Our data strongly support the concept that the window of opportunity for effective treatment of focal ischemia by reperfusion is narrow (of short duration). PMID- 2309273 TI - Neurologic complications of late prosthetic valve endocarditis. AB - We reviewed the records of 20 patients with late prosthetic valve endocarditis who were hospitalized at the University of Iowa between 1985 and 1988. There were 14 men and six women, aged 20-80 (mean 57.9) years. The infected valves were mechanical in 11 patients (six aortic and five mitral) and bioprosthetic in the other nine. Echocardiography in 12 patients demonstrated vegetations in one. Among the 20 patients, neurologic complications occurred in eight (40%), six of whom had mechanical valves (five mitral and one aortic). Infection with Staphylococcus aureus occurred in four of the eight patients (50%) with neurologic complications. Of the eight patients with neurologic complications, ischemic stroke was diagnosed in four, transient ischemic attacks in one, and intracranial hemorrhage in three. Prothrombin times at the time of the intracranial hemorrhage were 2.2, 1.5, and 1.3 times control in these three patients. Cerebral angiography done in four of the eight patients with neurologic complications failed to show mycotic aneurysms. Nine of the 20 patients (seven men and two women, mean age 66.8 years) died less than or equal to 90 days after the diagnosis of late prosthetic valve endocarditis. Half of the eight patients with neurologic complications died (three men and one woman, mean age 62.3 years), and all three patients with intracranial hemorrhage died. Our data suggest that the neurologic complications of late prosthetic valve endocarditis are more common with mechanical valves, particularly in the mitral position, and are associated with a high mortality. PMID- 2309274 TI - Cerebral amyloid angiopathy as a cause of subarachnoid hemorrhage. AB - Cerebral amyloid angiopathy is a pathologic condition characterized by the deposition of amyloid in the walls of small vessels in the cerebral cortex and meninges. Intracerebral hemorrhage is common in persons with this condition, but pure subarachnoid or subdural hemorrhage is rarely seen. Recently, the existence of two types of amyloid proteins related to cerebral amyloid angiopathy, beta protein and cystatin C, has been reported, and immunohistochemical methods using antisera to these proteins have become available. We describe a patient with fatal subarachnoid hemorrhage presumably caused by beta protein-type cerebral amyloid angiopathy, which was demonstrated immunohistochemically by using a monoclonal antibody to a synthetic peptide corresponding to residues 8-17 of beta protein. We suggest that beta protein-type cerebral amyloid angiopathy is a possible etiologic factor in subarachnoid hemorrhage of unknown cause. PMID- 2309275 TI - Cerebral venous thrombosis in a child with iron deficiency anemia and thrombocytosis. AB - We describe a 22-month-old boy with iron deficiency anemia and reactive thrombocytosis who developed vomiting, headache, mental status changes, and seizures. Computed tomography showed infarction of the basal ganglia and thalami. Magnetic resonance imaging revealed cerebral venous thrombosis, delineated the extent of the vascular and associated parenchymal involvement, showed the infarcts to be hemorrhagic (a finding not imaged by computed tomography due to our patient's depressed hemoglobin level), and obviated the need for invasive angiography. PMID- 2309276 TI - Leukoaraiosis and dementia. PMID- 2309277 TI - Acute basilar artery occlusive disease. PMID- 2309278 TI - Proceedings of the Fifteenth Congress of the Scandinavian Transplantation Society. Helsinki, May 18-20, 1989. PMID- 2309279 TI - Difference in B cell-induced transplantation tolerance to major histocompatibility complex antigens in irradiated and cyclophosphamide-treated chickens. PMID- 2309280 TI - Rat aortic allografts: a model for chronic vascular rejection. PMID- 2309281 TI - Lymphocytes bind to capillary endothelium during heart allograft rejection. PMID- 2309282 TI - Cytotoxic lymphocytes and lymphokine-activated killer cell-mediated lysis against rat kidney components. PMID- 2309283 TI - The specificity of B cells in rats rejecting kidney allograft. PMID- 2309284 TI - Peritubular capillary endothelium controls lymphocyte homing into rejecting kidney allograft. PMID- 2309285 TI - Chronic renal lesions in rats after long-term treatment with cyclosporine A. PMID- 2309286 TI - Up to 22 hour preservation of small bowel using a transplantation model in the pig. PMID- 2309287 TI - Artificial blood/intracellular-like solution for lung preservation in porcine single-lung allotransplantation: a morphologic study. PMID- 2309288 TI - Single lung allotransplantation in pigs: computed tomography in monitoring lung allografts. PMID- 2309289 TI - Heterotopic cardiac xenograft transplantation from mouse to rat. PMID- 2309290 TI - Cardiac transplantation from a blood group ABO-incompatible donor: a case report. PMID- 2309291 TI - The significance of repeated HLA-A, -B, and -DR mismatches in renal transplantation. PMID- 2309292 TI - Donor-specific transfusions in HLA-one haplotype-matched kidney transplantation. PMID- 2309293 TI - The role of HLA compatibility in renal transplantation from living donors: an analysis of 379 grafts. PMID- 2309294 TI - Lymphocele following renal transplantation: a clinical study. PMID- 2309295 TI - Renal replacement therapy in the cyclosporine era: results of a national transplantation program. PMID- 2309296 TI - Kidney transplantation in children in Gothenburg. PMID- 2309297 TI - Renal transplantation in children with congenital nephrotic syndrome of the Finnish type. PMID- 2309298 TI - Renal transplantation in children: renal functional follow-up of cyclosporine treated children. PMID- 2309299 TI - Central nervous system complications in renal transplantation in children. PMID- 2309300 TI - Kidney transplantation in the elderly in Finland. PMID- 2309301 TI - Soluble interleukin-2 receptor: a novel parameter of renal graft rejection. PMID- 2309302 TI - Breakthrough of liver transplantation in the Nordic countries. PMID- 2309303 TI - Hypoxemia cured by liver transplantation. PMID- 2309304 TI - Inferior mesenteric vein cannulation for veno-venous bypass during liver transplantation: alternative access in difficult hilar dissection. PMID- 2309305 TI - Percutaneous transhepatic cholangioscopy in biliary complications after liver transplantation. PMID- 2309306 TI - Ultrastructure in liver preservation with Eurocollins and UW solutions. PMID- 2309307 TI - Benefits and drawbacks with the use of pancreatico-duodenal grafts in pancreatic transplantation with enteric drainage. PMID- 2309308 TI - Heart transplantation: state-of-the-art in 1989. PMID- 2309309 TI - Evaluation and selection of the heart transplantation patient. PMID- 2309310 TI - Heart transplantation in Gothenburg, 1988 through 1989. PMID- 2309311 TI - Heart transplantation in Finland, 1985 through 1989. PMID- 2309312 TI - Surgery after heart transplantation. PMID- 2309313 TI - Improved survival in marrow recipients above 30 years of age with better prevention of graft-versus-host disease. PMID- 2309314 TI - Bone marrow transplantation for metabolic disorders at Huddinge Hospital. PMID- 2309315 TI - Serum erythropoietin levels after bone marrow transplantation. PMID- 2309316 TI - Which bone marrow transplant recipients are at risk of acquiring life-threatening fungal infections? PMID- 2309317 TI - Predisposing factors for development of oral lesions after allogeneic bone marrow transplantation. PMID- 2309318 TI - Immunologic properties of a sulphate conjugate of cyclosporine A. PMID- 2309319 TI - Five-year follow-up of graft function and urinary protein excretion in kidney transplant patients immunosuppressed with cyclosporine or azathioprine. PMID- 2309320 TI - Steroid-resistant rejection: the effect of ATG on renal allograft survival. PMID- 2309321 TI - The incidence and diagnosis of invasive fungal infections in liver transplant recipients. PMID- 2309322 TI - Infections in cyclosporine-treated kidney graft recipients: beneficial effect of cotrimoxazole prophylaxis. PMID- 2309323 TI - Change in intrarenal sodium reabsorption following donor nephrectomy. PMID- 2309324 TI - Are older donors acceptable for heart transplantation? PMID- 2309325 TI - Multiple organ donation does not influence kidney quality. PMID- 2309326 TI - The physician's role as asker in obtaining organ donations. PMID- 2309327 TI - Procurement of liver allografts from non-heart beating donors. PMID- 2309328 TI - Atheromatous embolization as a cause of increasing creatinine levels in a renal transplant patient. PMID- 2309329 TI - A study of cadaveric fetal adrenal used for adrenal transplantation to treat Addison's disease: thirteen cases reported. PMID- 2309330 TI - Raised plasma levels of tumor necrosis factor in heart allograft rejection. PMID- 2309331 TI - Binding of cyclosporine A to human serum lipoproteins. PMID- 2309332 TI - Temporal T cell suppression and impaired host responsiveness to nonvascularized neonatal cardiac allografts in experimental hepatic failure. PMID- 2309333 TI - Decreased kallikrein excretion in renal transplant treated with cyclosporine A. PMID- 2309334 TI - TiPS receptor nomenclature supplement. PMID- 2309335 TI - Too early to subtype imidazoline receptors. PMID- 2309336 TI - [Evaluation of the early screening for breast cancer using self examination]. PMID- 2309337 TI - [The exfoliation syndrome in Tunisia]. PMID- 2309338 TI - [Results of a study of nicardipine (YC 93) in arterial hypertension in cardiology practice]. PMID- 2309339 TI - [Mother's attitude and behavior in acute diarrhea]. PMID- 2309340 TI - [A case of diffuse pulmonary fibrosis in a diamond cutter]. PMID- 2309341 TI - [Sickle cell anemia and pregnancy]. PMID- 2309342 TI - [Cerebral toxoplasmosis in AIDS: apropos of a case]. PMID- 2309343 TI - [Budd-Chiari syndrome and total villous atrophy in children: apropos of 3 case reports]. PMID- 2309344 TI - [Osteosynthesis of patellar fractures using the principle of support wires of 126 cases]. PMID- 2309345 TI - [Endotoxinemia--clinical significance]. PMID- 2309346 TI - [Blood sedimentation rate in healthy persons]. AB - The erythrocyte sedimentation rate was determined using the Westergren method in 4,202 consecutive blood donors aged 18-65 years. The distribution of the values was log normal for both females and males. The median value was highest in females for all age classes and although both the median and the range rose in both sexes with increasing age, the increase was most pronounced in females. Used as a screening test, the fraction of false positives showed a marked rise after age 45 years using cut-off values of 15 and 20 mm/hr, while the increase took place after age 55 years when 25 mm/hr was applied. The results point to increasing the most frequently used cut-off values and one cut-off value for premenopausal women and another, higher, value for postmenopausal women may be considered. For men a single cut-off value seems adequate. PMID- 2309347 TI - [Cerebral apoplexy. Incidence and duration of hospitalization]. AB - The incidence rates of hospitalization for acute stroke (subarachnoid haemorrhage not included) in three municipalities in Copenhagen County, Denmark, were assessed in order to provide a basis for estimating the current need for hospital care and rehabilitation. The crude annual incidence rate was 2.61 per 1,000 population. Adjusted for age and sex by direct standardization to the Danish population, the annual incidence rate was 1.88 per 1,000 population. If hospitalizations, caused by sequelae from former strokes are included, the crude and adjusted rates were 3.00 and 2.16, respectively. The average time spent in hospital was 33.7 days (median: 20 days). If these figures are extended to the entire Danish population of over 5 million, 1,000 hospital beds are estimated to be occupied by stroke patients at any given time. PMID- 2309348 TI - [Alternative possibilities to emergency admissions to a medical department]. AB - On the basis of a questionnaire to general practitioners who had referred 200 patients greater than or equal to 60 years as emergencies to a non-specialized medical ward, possible alternative possibilities to the emergency hospitalization are assessed. It proved possible to obtain information and replies about 175 patients who were, therefore, included in this investigation. As a considerable proportion of the socially-conditioned admissions occurred during daytime hours and these were referred by practitioners who knew their patients well (40% described themselves as knowing these patients very well) it was found that the referring practitioners were well aware of alternatives to emergency hospitalization. The practitioners referring the patients described 36 out of the 175 patients as socially-conditioned and 2/3 of these as sociomedically conditioned. In agreement with this, the authors found that 70% of the socially conditioned admissions had a concurrent somatic diagnosis most frequently in the form of pulmonary of cardiac disease. Nevertheless, the referring physicians considered that 33 (93%) of the admissions could either be be entirely avoided (81%) or that admission could be postponed (12%). The requisites for this were primarily easy access to nursing homes or to emergency home nursing facilities. PMID- 2309349 TI - [Exposure of Danish workers to trichloroethylene during the period 1947-1987]. AB - Trichloroethylene, an organic solvent from the group of chlorinated hydrocarbons, has been employed throughout the greater part of this century particularly for degreasing of metals, dry cleaning and as a content in glue and lacquer. Biological monitoring of workers exposed to trichloroethylene as current health supervision has been employed in Danish factories since 1947 as the metabolite trichloroacetic acid in the urine provides an indication of the degree of exposure during the preceding week. In the present investigation, a review was undertaken of all measurements of trichloroacetic acid notified to the Danish Labour Inspection Service during the period 1947-1987 in order to obtain an impression of the historical development in the level of exposure. A total of 2,272 biological measurements distributed among 330 factories, reveal exposure of about the same level from the middle of the fifties to the middle of the seventies but with a distinct fall during the period, as the average value during the first five-year period was 82 mg/l as compared with 18 mg/l at the end of this 40-years period. These data are supplemented by case-histories from the earliest part of the period described by doctors from the Danish Labour Inspection Service. PMID- 2309350 TI - [Treatment of esophageal achalasia using Heller's method]. AB - The long-term results after Heller's myotomy for oesophageal achalasia were illustrated by questionnaire sent to 38 out of the original 47 patients submitted to operation during the ten-year period 1.7.1973-30.6.1983. Nine patients had died from other causes during the follow-op period. The minimum period of observation for the remaining patients was five years and the mean period of observation was 10.3 years. Thirty-six questionnaires were returned (95%). 75% of the patients were satisfied with the results of operation but only 25% were symptom-free. The commonest symptom was dysphagia (56%) followed by reflux problems (50%). Every third patient had discomfort from the scar. All of the 25% of the patients who were not satisfied with the result of operation had dysphagia. On the basis of these observations, the authors consider that Heller's myotomy should be reserved for patients on whom dilatation treatment has proved unsatisfactory. PMID- 2309351 TI - [The clinical relevance and reproducibility of pedal pulse palpation]. AB - The object of the present investigation was to investigate the diagnostic information which can be obtained by pedal pulse palpation. This is done by relating the findings on pulse palpation to the measured distal systolic blood pressure and comparison of these results with those of previous examinations where the connection between the distal systolic blood pressure and the prognosis is illustrated. In addition, the reliability of pulse palpation was assessed by an inter-observer investigation. Fifty four patients (average age 66 years) suspected of occlusive arterial disease participated in the investigation. Three observers undertook pulse palpation on the foot in a randomized sequence. The pulse in a foot was defined as the pulse in the dorsalis pedis artery and/or the pulse in the posterior tibialis artery. After this, the distal systolic blood pressure was measured in the patients with the strain gauge technique. Considerable inter-observer agreement was found (kappa-values between 0.66 and 0.76). Provided an observer found the pulse present, severe occlusive arterial disease could be excluded (ankle index less than 50%, toe pressure less than or equal to 30 mmHg). Absence of pulse in a foot provides a high probability for an ankle index less than or equal to 90% and thus a high probability for presence of occlusive arterial disease, but the extent of this cannot, however, be described. PMID- 2309352 TI - [Induction of early first trimester abortion with a prostaglandin E1 analogue. A pilot study]. AB - A pilot investigation employing prostaglandin (PG) induced early abortion (maximal 56 days of menostasia) was planned with the object of investigation whether this non-surgical method was as effective, safe and acceptable as vacuum aspiration. The investigation was planned to include 20 women to be treated with 1 mg PGE1-vagitories at intervals of three hours up to five times in 24 hours. If abortion did not occur after 24 hours as assessed by gynaecological examination and sonography, the uterus was evacuated. After seven women had participated, the investigation was abandoned because of complications and violent pain in several women and because very few of the woman ashed to participate desired to do so, i.e. they preferred vacuum aspiration under general anaesthesia. It is concluded that the method employed here did not prove acceptable for Danish women on account of the severe pain involved and the protracted course of the procedure. PMID- 2309353 TI - [Glycosylated hemoglobin (HbA1c) and acute hemolytic anemia]. AB - The concentrations of glycosylated haemoglobin (HbA1c) were determined in eight patients with acute haemolytic anaemia and were found to be significantly lower than in a control group of 16 patients. A case history is presented in which HbA1c was employed as longitudinal parameter of haemolysis. It is concluded that in haemolytic anaemia in non-diabetic patients, HbA1c is a specific parameter of haemolysis which may be employed as a supplement to the traditional parameters of haemolysis. PMID- 2309355 TI - [Candidiasis of the stomach as a complication of hiatal hernia surgery]. AB - Candidiasis in the stomach after hiatus hernia sac operation has not previously been reported in the literature. We present a case in which a 46 year old woman developed candidiasis of the stomach, two months after hiatus hernia sac operation. The disease was primarily diagnosed radiologically and was later confirmed by gastroscopy and culture of gastric fluid. The pentagastrin test was performed six months after the operation and showed significantly reduced acid production. The most probable explanation for the condition is peroperative accidental lesion of branches of the vagus nerve resulting in reduced acid production thus facilitating growth of gastric candidiasis. PMID- 2309354 TI - [Inverted papilloma of the nose and nasal sinuses. Incidence, long-term course, therapeutic results]. AB - Inverted papilloma is an unusual tumour in the nose and nasal sinuses with a marked tendency to recurrence following surgical treatment and with a greatly increased risk for synchronous or metachronous development of carcinoma. A retrospective investigation comprising 42 patients with histological revision revealed an incidence of 0.6/100,000 per annum. Two patients had also carcinomata. No significant differences were observed between the recurrence rates following simple excision, excision via the maxillary sinus or via lateral rhinotomy. Follow-up control for ten years is recommended. PMID- 2309356 TI - [Compulsory admissions]. PMID- 2309357 TI - [Occupational risk of HIV infection among health personnel]. PMID- 2309358 TI - [The medical school at the University of Copenhagen]. PMID- 2309359 TI - [Diagnosis of ascites]. PMID- 2309360 TI - [Assessment of the risk of cardiovascular disease on the basis of total serum cholesterol in a population of young Danish women and men]. AB - In this investigation the distribution of total cholesterol in the serum in a population of 364 medical students in the age group 22-32 years is assessed. The average value was 5.27 mmol/l for women and 5.08 mmol/l for men. 5% of the women and 2% of the men had values which exceeded 7.0 mmol/l and were thus in a group where treatment with diet or medicine may be considered, according to the recommendations from the Danish Association for Internal Medicine. In the group investigated here, the authors did not find any significant change in total cholesterol with age and, similarly, no significant seasonal variation was encountered. PMID- 2309361 TI - [Bacteremia caused by zoonotic Salmonella types in greater Copenhagen in 1984 1988]. AB - The five departments of clinical microbiology in Greater Copenhagen have together carried out a retrospective review of bacteraemia caused by the zoonotic Salmonella serotypes in the period 1984-1988 in the municipalities of Copenhagen and Frederiksberg and in the County of Copenhagen. A gradual increase in frequency was observed from 11 cases in 1984 to 58 cases in 1988. The serotype most commonly isolated was Salmonella dublin followed by Salmonella enteritidis and Salmonella typhimurium. S. dublin was found to be more invasive and more virulent than the other serotypes. Predisposing factors were present in 56% of the patients; the commonest of these was malignant disease. Fatal or complicated course of the disease were observed more frequently in predisposed patients than in persons who had previously been healthy. A total of 17% of the patients died and one fourth of these had ruptured aortic aneurysm probably on account of Salmonella arteritis. 20% developed recurrence of bacteraemia while in the remaining patients the disease ran an uncomplicated course. It is concluded that the marked increase in the number of cases and the serious course taken by the infection demonstrate a definite need for increased prophylactic efforts in the food industry. PMID- 2309362 TI - [Nodular pulmonary amyloidosis]. AB - Amyloidosis limited to the lower respiratory tract is a relatively rare condition. It may be either tracheobronchial or parenchymal, and the parenchymal form may be either nodular or diffuse. A case of nodular pulmonary amyloidosis is presented. PMID- 2309363 TI - [Isolated sphenoid sinusitis]. AB - A case of isolated sphenoid sinusitis following an influenza-like illness in a woman aged 34 years is presented. The importance of the diagnosis and treatment is emphasized. PMID- 2309364 TI - [Cholesterol should be treated seriously]. PMID- 2309365 TI - [Benefits of cholesterol reduction]. PMID- 2309366 TI - [Cholesterol--once again]. PMID- 2309367 TI - [What does the reduction of cholesterol benefit?]. PMID- 2309368 TI - [Drug therapy of symptoms in peripheral diabetic neuropathy. Tricyclic antidepressive agents and other drugs]. PMID- 2309369 TI - [Levothyroxine in the treatment of hypothyroidism]. PMID- 2309370 TI - [Whooping cough epidemiology in Denmark prior to and after the introduction of whooping cough vaccination. Protective effect of the vaccine and herd immunity]. AB - The epidemiology of whooping cough in Denmark is described on the basis of the notified cases of the disease. The frequency of whooping cough has decreased to approximately one sixteenth of the previous level in children following the introduction of vaccination for whooping cough in 1961. Following change to a programme with only three vaccinations with a weaker, non-aluminium-adsorbed pure whooping cough vaccine in 1970, whooping cough became again slightly more frequent in the nineteen seventies and eighties. No definite reduction in the proportion of cases of whooping cough among infants could be detected although this was what the 1970 programme was particularly aimed at. Isolated deaths from whooping cough still occurred in the eighties, all of these among unvaccinated infants. The risk of whooping cough in an unvaccinated child is approximately one sixth of the risk prior to introduction of vaccination. In a vaccinated child, the risk, as judged from the notified cases, is one twentieth of the risk during the time prior to introduction of vaccination. In all age groups "herd immunity" is considered to have contributed considerably to the reduced incidence. The incidence in Denmark is, however, high compared with the incidence in some other industrialized countries. A vaccination programme with more numerous whooping cough vaccinations and possibly with a more immunogenic vaccine may be recommended on the basis of the strategy aimed at keeping the incidence of whooping cough, and thus the risk of exposure, as low as possible. PMID- 2309371 TI - [Delayed diagnosis of epiphysiolysis capitis femoris]. AB - The prognosis in epiphysiolysis of the head of the femur (ECF) depends on immediate treatment in the earliest stage of the disease. The reasons for and the extent of delayed diagnosis of slipping of the epiphysis in the hip were analysed in 56 children (72 hips) with ECF. The median total delay was six months with a delay of one month due to the patient and delay of three months due to the doctor. Pain in the lower limbs not related to the hip, including pain in the knee, occurred in 1/3 of the patients and resulted in more extensive delays due to the doctor (median four months). Other reasons for delay due to the doctor were erroneous interpretation of the x-ray films (14 patients). The most characteristic clinical finding was limited internal rotation of the affected hip. Comparison with the literature revealed that delay in the diagnosis of ECF has not been reduced during the past 35 years. Clinical examination of the hips should be undertaken in any child who complains of pain in the knee or thigh. If internal rotation is limited, x-ray examination including Lauenstein's projection should be carried out or the child should be referred to a department of orthopaedic surgery on account of suspected hip disease. PMID- 2309372 TI - [Body temperature measurement. Rectal--oral?]. AB - The reliability of daily routine oral temperature measured by the nursing staff with an electronic thermometer was tested by comparing the measurements with rectal temperature measured with a mercury thermometer. In each patient, rectal temperature was measured by the author just after the oral temperature measurement. The nursing staff was not informed about the investigation. In a small group of 12 patients with clinical suspicion of fever, six patients had normal oral temperatures (less than or equal to 37 degrees C). Three of these had rectal temperatures greater than or equal to 38 degrees C. In another group of 11 patients selected because of a normal oral morning temperature (less than or equal to 36.5 degrees C) seven had slightly elevated rectal temperatures (37.1 37.3 degrees C). Thus, a significant number of patients in the two groups had false normal oral temperatures. In five of the 12 and four of the 11 patients, the rectal temperature was 1 degree C or more above the oral temperature. The reason for measuring too low oral temperatures seems to be difficulties in avoiding external influence. The use of different measuring points each with its own lower limit of fever might lead to misinterpretation of the patients' temperature curve. Abolition of the mercury thermometer represents environmental progress. Unfortunately the sensor of the electronic thermometer, which is discarded after use, contains considerable amounts of different metals, mainly copper but also heavy metals. The rectum should remain the site of measurement of body temperature and the digital reuse thermometer the measuring device. PMID- 2309373 TI - [Total hip prosthesis infected with Salmonella dublin]. AB - In 1983, the bovine-specific Salmonella Dublin was demonstrated in man in Denmark. The organism is frequently isolated from blood but rarely causes gastroenteritis. The frequency of infection following hip replacement is less than 2% with Staphylococcus aureus as the commonest agent while Gram-negative rods are rarer but are considered to be more serious. Infection around a hip replacement frequently implies that the prosthesis must be removed. A case in which a hip replacement was infected with Salmonella Dublin is described here. The patient had looked after infected calves until operation and it is presumed that the prosthesis was infected haematogenically, either primarily or later. The infection was controlled surgically without removal of the prosthesis which was stable. Even although the condition is satisfactory six months after revision, the long-term prognosis is poor. PMID- 2309374 TI - [Gluteal compartment syndrome]. AB - The gluteal compartment syndrome is a condition which has rarely been described. Most frequently, it is caused by violent injury. A case which was precipitated by intramuscular injection in connection with anticoagulation treatment and which involved the sciatic nerve is described. PMID- 2309375 TI - [Gastric banding in the treatment of severe obesity]. PMID- 2309376 TI - Measurements of frequency spectra of transmission coefficients to ultrasound through trapped microbubbles. AB - Techniques which use hydrophobic polycarbonate thin sheets containing randomly spaced, fairly uniform small pores immersed in water to trap air bubbles have been found to be useful in biophysical experiments. The utilization of broadband polyvinylidene fluoride transducers in this work made it possible to measure a continuous frequency spectrum of the transmission coefficient of the trapped bubbles. The results of the measurements show: (1) the frequency response curve of the bubble ensemble is much broader than that of a single bubble predicted by theory; and (2) as the incident sound pressure at a micropore membrane increases from 110 to 660 Pa the resonance frequency of bubbles shifts to lower values by as much as 7%. PMID- 2309378 TI - Ovine mesangiocapillary glomerulonephritis type I and crescent formation. AB - Morphologic examination of four Finnish Landrace mixed-breed lambs, 27 to 35 days of age, affected with mesangiocapillary glomerulonephritis type 1, demonstrated a progressive glomerulonephritis. By 27 days of age, three lambs had crescents in 58 to 93% of glomeruli. These three lambs were also uremic. The accelerated rate of crescent formation was attributed to infiltrating polymorphonuclear leukocytes and monocytes, the result of discontinuities (gaps) in the glomerular basement membrane, and to the loss of the integrity of Bowman's capsule. In the three lambs, platelets were identified adjacent to the endothelium or denuded glomerular basement membrane. Two distinctly different types of crescents were noted, apparently dependent on the integrity of Bowman's capsule. One type resulted from the influx of inflammatory cells and dissociation of parietal epithelial cells from Bowman's capsule. The other type was more extensive and contained collagen and was associated with damage to Bowman's capsule resulting in cellular infiltration from the interstitium and sclerosis. Based on morphologic similarities, ovine mesangiocapillary glomerulonephritis is a suitable model for studying the pathogenesis and treatment of mesangiocapillary glomerulonephritis type 1 in human beings. PMID- 2309377 TI - Congenital spinal stenosis in beef calves in western Canada. AB - Nineteen calves with a clinical history of posterior weakness or ataxia were examined at necropsy. Dorsoventral narrowing of the vertebral canal and myelopathy were found in the thoracic and lumbar areas of the spinal cord; vertebral metaphyseal growth plates had focal areas of premature closure. Malformation of the cranial base and hydrocephalus were also observed. Shortening of long bones and malformation of long bone epiphyses were prominent findings and were associated with focal premature closure of metaphyseal growth plates. The cause of these lesions is unknown; possible causes, including a maternal deficiency of manganese, are discussed. PMID- 2309379 TI - The causes of glaucoma in cats. AB - The cause of glaucoma in 131 enucleated eyes from 128 cats was determined in a retrospective histologic study. Obliteration of the ciliary cleft by diffuse iridal melanoma (38 eyes), or other neoplasms (14 eyes), or by the presence of idiopathic lymphocytic-plasmacytic anterior uveitis (53 eyes) were the most frequent lesions likely to explain the development of glaucoma. Secondary changes of inner retinal atrophy, optic disc cupping, scleral thinning with megaglobus, and atrophy of ciliary processes were similar to those described in dogs and human beings with chronic glaucoma. In light of the duration and severity of the glaucoma, the degree of inner retinal atrophy was often less than expected. Diffuse corneal edema and breaks in Descemet's membrane, changes typical of glaucoma in other species, were rarely detected. Eyes with chronic uveitis and glaucoma had collapsed ciliary clefts, iridoscleral adhesions, and posterior displacement of the iris. We were unable to determine whether these changes were consequences of the uveitis and thus responsible for the development of glaucoma, or if they were merely the result of the chronic glaucoma itself. PMID- 2309380 TI - The pathogenesis and significance of pre-iridal fibrovascular membrane in domestic animals. AB - Histologic examination was made of 1,419 globes from domestic animals (964 dogs, 374 cats, 41 horses, and 40 cattle) with ocular disease; pre-iridal membranes (rubeosis iridis) were found in 98. The membranes originated as endothelial budding from the anterior iridal stroma and seemed to mature into fibrous or fibrovascular membranes that were often followed by hyphema or, occasionally, glaucoma. Pre-existent disease in the 98 affected globes included chronic endophthalmitis (27/98), chronic glaucoma (24/98), anterior uveal melanoma (15/98), ciliary body adenoma (14/98), neoplasms metastatic to the eye (8/98), and chronic retinal detachment (6/98). In terms of likelihood of occurrence, pre iridal membranes seen in 21% (6/21) of globes with retinal detachment, 19% (14/75) of those with ciliary body adenomas, 14% (24/167) of those with chronic glaucoma, and 10% (15/158) of those with anterior uveal melanoma. They were detected with greatest relative frequency in horses (9/41) followed by dogs (83/964), cats (5/374) and cattle (1/40). These membranes, which are rarely detected by clinical examination, probably form in response to angiogenic factors released by ischemic retina, by neoplasms, or by leukocytes involved in ocular inflammation. PMID- 2309381 TI - Canine extraskeletal osteosarcoma and chondrosarcoma: a clinicopathologic study of 14 cases. AB - Canine extraskeletal osteosarcomas are extremely rare tumors. Over a period of 25 years at the Animal Medical Center, approximately 1,000 cases of skeletal osteosarcomas have been diagnosed. During the same period 11 cases of extraskeletal osteosarcomas and three extraskeletal chondrosarcomas were diagnosed. Tumors of the mammary gland were excluded. Extraskeletal osteosarcomas were found in the adrenal gland, eye, gastric ligament, ileum, kidney, liver, spleen, testicle, and vagina. The chondrosarcomas were found in the mitral valves, lungs, and omentum. The mean age of the dogs with extraskeletal osteosarcoma was 11 years, and the mean age of the dogs with extraskeletal chondrosarcoma was 14 years. The The sizes of the tumors ranged from 3 cubic centimeters to 8,315 cubic centimeters. Osteoblastic osteosarcomas were the most common histologic type (7/11, 63.6%); there was a single case of each of the following: fibroblastic, fibrous histiocytic, chondroblastic, and mixed osteo chondroblastic osteosarcoma. Two of the dogs with chondrosarcomas had mesenchymal chondrosarcomas involving the lungs and omentum. The remaining dog had a regular chondrosarcoma involving the mitral valve. Distant metastases were present in seven of 11 dogs with extraskeletal osteosarcoma and in none of the dogs with chondrosarcoma. In contrast to human beings, in which most extraskeletal osteosarcomas occur in the soft tissues and the extremities, most canine extraskeletal osteosarcomas develop in the visceral organs. PMID- 2309382 TI - Congenital portosystemic shunts in three pigs and one calf. PMID- 2309383 TI - Spleno-mesenteric-renal venous shunt in two dogs. PMID- 2309384 TI - Amputation neuroma of docked tails in dogs. PMID- 2309385 TI - Clinical and morphologic features of post-traumatic ocular sarcomas in cats. PMID- 2309386 TI - Naturally occurring malignant melanoma in the South American opossum (Monodelphis domestica). PMID- 2309387 TI - Use of a tiletamine-zolazepam mixture to immobilise wild grey seals and southern elephant seals. AB - A mixture of tiletamine and zolazepam at a combined dose of 1 mg/kg was a reliable and safe agent for immobilising wild grey seals (Halichoerus grypus) and southern elephant seals (Mirouga leonina). The agent had a number of advantages over all the other agents used previously. PMID- 2309388 TI - Field trials of the anthelmintic efficacy of nitroscanate and mebendazole in dogs. AB - The efficacies of nitroscanate and mebendazole against nematodes and Dipylidium caninum were compared by the examination of the faeces of 155 dogs. In unweaned puppies nitroscanate acted significantly faster and was significantly more effective than mebendazole against Toxocara canis. In adult dogs, both drugs had a low efficacy against Trichuris vulpis but a similarly good efficacy against other nematodes, with a tendency for nitroscanate to be more effective in reducing the prevalence of Ancylostoma caninum. Nitroscanate reduced the prevalence of D caninum infections considerably more than mebendazole. PMID- 2309389 TI - Aspergillosis in gentoo penguins (Pygoscelis papua) at Edinburgh Zoo, 1964 to 1988. AB - Aspergillosis was the commonest cause of death in gentoo penguins (Pygoscelis papua) at Edinburgh zoo from 1964 to 1988. Chicks were the most susceptible group and 14 per cent of hatched birds died of the disease (47 per cent of post mortem diagnoses) although in two years no cases were recorded and in two other years there were outbreaks which killed more than 50 per cent of the birds hatched. There was no correlation between the size of the colony and the prevalence of the disease but the climate during the rearing and weaning periods may have influenced the prevalence. The majority of cases of aspergillosis occurred between July and September and affected two- to three-month-old chicks shortly after they had been moved from their parents to a creche area for hand-feeding. No links were found between the occurrence of the disease and the date of hatching or the nest site, or whether the chicks were single, first or second hatched twins, or with their weights, but the progeny of one parental pair were found to be overrepresented and more males than females died of the disease. Adult cases occurred sporadically and males were significantly more susceptible than females (P less than 0.05). Neither vaccination with a killed suspension of Aspergillus fumigatus nor therapeutic treatment with ketoconazole were effective in reducing the incidence of aspergillosis, although the late diagnosis of the disease was probably the main cause for the failure of these treatments. PMID- 2309390 TI - Clinical response of cattle to experimental infection with bovine ephemeral fever virus. AB - As part of a study of the pathology and pathogenesis of bovine ephemeral fever virus infection 44 cattle were infected by the intravenous injection of virulent virus. Thirty-eight animals responded clinically and detailed haematological and serological data were obtained from 10 of them. Inappetence was the only clinical sign observed before the onset of fever. The temperature response was characteristically biphasic, with the second peak occurring 12 to 24 hours after the first. The only consistent haematological response was an increase in the numbers of circulating neutrophils with a concurrent decline in the numbers of mononuclear leucocytes. There were no detectable changes in plasma or blood volume, packed cell volume, red cell count, haemoglobin concentration, serum calcium, magnesium, phosphorus and creatinine concentrations, or aspartate aminotransferase activity. Viraemia was demonstrated on either the first or second day of clinical disease and lasted for at most 48 hours. Low levels of neutralising antibody could be detected within one or two days after the cessation of viraemia. Six antibody-free animals did not respond clinically to injection with virulent virus, and did not develop detectable viraemia or a serum neutralising antibody response. PMID- 2309391 TI - Dermatitis in a cat associated with Spilopsyllus cuniculi. PMID- 2309392 TI - Atypical nodular leishmaniasis in two dogs. PMID- 2309393 TI - BSE in Oman. PMID- 2309394 TI - Caesarean sections on BSE cows. PMID- 2309395 TI - Inheritance of BSE. PMID- 2309396 TI - Monensin and ovine toxoplasmosis. PMID- 2309397 TI - Definition of progressive atrophic rhinitis. PMID- 2309398 TI - Lameness in kittens after vaccination. PMID- 2309399 TI - Testing blood lead levels. PMID- 2309400 TI - Alternative medicine. PMID- 2309401 TI - COSHH regulations: the vet's responsibility in law. PMID- 2309402 TI - Trade in rodents. PMID- 2309403 TI - Clinical, haematological and biochemical findings and the results of treatment in cattle with acute functional pyloric stenosis. AB - The clinical features and changes in blood and rumen fluid, and the results of therapy are described in 10 cows suffering from acute functional pyloric stenosis. The general condition of the cows was moderately to severely disturbed. The abdomen of most of them was distended on one or both sides and the rumen was excessively full. Defecation was reduced or absent. In most of them there was moderate or severe abomasal reflux-syndrome. Exploratory laparotomy or slaughter revealed a grossly distended abomasum which was filled with ingesta but not displaced. The omasum, reticulum and rumen of most of the cows were dilated secondarily and filled with ingesta. Six of the cows were treated by the administration of a solution of sodium chloride, glucose and potassium chloride intravenously, and metoclopramide intramuscularly. Five cows recovered within a short time, general condition, appetite and defecation were again normal and the abomasal and ruminal function returned within three days. PMID- 2309404 TI - Dietary transmission of bovine spongiform encephalopathy to mice. PMID- 2309405 TI - Preliminary evidence of the experimental transmissibility of bovine spongiform encephalopathy to cattle. PMID- 2309406 TI - Reduction of sulphadimidine contamination in pig feedingstuffs. PMID- 2309407 TI - Digital dermatitis control. PMID- 2309408 TI - Evaluation of acid-base disturbances. PMID- 2309409 TI - Bovine fetal encephalitis and myocarditis associated with protozoa. PMID- 2309410 TI - Urinary incontinence due to urovagina. PMID- 2309411 TI - Use of phenolic and chlorocresol disinfectants near dairy premises. PMID- 2309412 TI - 'A woman is not only a woman'. PMID- 2309413 TI - Certificate examination in veterinary radiology. PMID- 2309414 TI - Puppy farms. PMID- 2309415 TI - Hypercalcaemia and soft tissue mineralisation associated with lymphosarcoma in two horses. AB - Two horses with deposits of lymphosarcoma, one in the spleen, the other in the mediastinum, several lymph nodes and kidneys, lost weight rapidly and became depressed and weak. They were hypercalcaemic and post mortem examination revealed extensive calcification of the heart and major vessels. There was no evidence of bone marrow metastases in the one horse whose marrow was examined, and the thyroid and parathyroid glands of both horses were grossly normal. PMID- 2309416 TI - COSHH regulations and the veterinary practitioner. PMID- 2309417 TI - Effect of preslaughter experience on behaviour, plasma cortisol and muscle pH in farmed red deer. AB - Three groups of farmed red deer were shot in the field, three groups were slaughtered on the farm and three groups were transported to commercial slaughterhouses. The behaviour of the animals was observed and peripheral plasma cortisol concentrations were measured immediately after slaughter and neck muscle pH was measured 24 hours after slaughter. The deer could be handled and herded without agitation when only one unhindered direction was open to them and nothing in the environment caused alarm. Shallow angled loading ramps were preferable. Deer shot in the field and deer penned without handling had low average plasma cortisol concentrations (less than 7 ng/ml) and a muscle pH less than 5.74 whereas deer which had been herded on the farm, or transported to a slaughterhouse, had high cortisol concentrations (greater than 20 ng/ml) and a muscle pH above 5.74. However, only four of 66 male deer transported to a slaughterhouse had a muscle pH above 6.0, the pH associated with dark cutting meat in red deer. PMID- 2309418 TI - Weak calf syndrome and parenteral selenium supplementation. PMID- 2309419 TI - Bovine digital dermatitis. PMID- 2309420 TI - Idiopathic megaoesophagus in a pregnant heifer. PMID- 2309421 TI - Bovine spongiform encephalopathy. PMID- 2309422 TI - Salmonella: time for a change. PMID- 2309423 TI - Evaluation of acid-base disturbance. PMID- 2309424 TI - Anaesthesia following medetomidine. PMID- 2309426 TI - Neutering cats and dogs. PMID- 2309425 TI - Lameness in kittens after vaccination. PMID- 2309427 TI - Puppy farms. PMID- 2309428 TI - Tail docking. PMID- 2309429 TI - Treatment of pyometra in the bitch. PMID- 2309430 TI - Porcine parvovirus survey. PMID- 2309431 TI - Dystocia in British cattle. PMID- 2309432 TI - Inheritance of BSE. PMID- 2309433 TI - Alternative medicine. PMID- 2309434 TI - Meat hygiene. PMID- 2309435 TI - Review of product licences. PMID- 2309436 TI - Welfare of draught animals. PMID- 2309437 TI - Nucleotide sequence of the tick-borne, orthomyxo-like Dhori/Indian/1313/61 virus envelope gene. AB - The complete nucleotide sequence of the fourth largest segment of single-stranded RNA of the tick-borne, orthomyxo-like Dhori/Indian/1313/61 virus was determined by using cloned cDNA derived from infected cell mRNA. The fourth RNA contains 1586 nucleotides and can code for a protein of 521 amino acids with a molecular weight of 58,675 Da. The predicted polypeptide possesses an amino-terminal hydrophobic region that may function as a signal sequence to initiate translocation across the endoplasmic reticulum membrane and a carboxyl-terminal hydrophobic region that could serve as a stop transfer sequence for anchoring this protein in the membrane. The envelope protein of Dhori virus does not display significant amino acid sequence homology with any of the envelope proteins (hemagglutinin or neuraminidase) of the influenza virus family members (or any other virus group) suggesting that the Dhori envelope protein is unique and may at least in part account for its divergent biological properties with other orthomyxoviruses. PMID- 2309438 TI - Protection against tobacco mosaic virus infection in transgenic plants requires accumulation of coat protein rather than coat protein RNA sequences. AB - Transgenic tobacco plants which express a chimeric gene encoding the tobacco mosaic virus (TMV) coat protein (CP) and the TMV 3' untranslated region are protected against infection by TMV. In this study chimeric genes that encode the sequences representing the TMV CP subgenomic RNA, but do not produce protein (because of removal of the initiation codon), and RNA that lacks the tRNA-like sequence of the TMV 3' end were expressed in transgenic plants. Only plants that accumulated CP, regardless of the presence of absence of the 3' end of TMV-RNA, were protected against infection by TMV. The results indicate that the CP per se, rather than TMV RNA, is responsible for the resistance to infection by TMV. Furthermore, the degree of protection is dependent upon the level of accumulated CP. PMID- 2309439 TI - Consolidation of intramolecular disulfide bonds in influenza virus hemagglutinin as an element of intracellular maturation. AB - Electrophoretic behavior of influenza virus hemagglutinin during SDS electrophoresis in polyacrylamide gel is critically dependent on the life time in the infected cells and also on the conditions of sample preparation and analysis. During electrophoresis of total cell lysate proteins under nonreducing conditions the short-labeled hemagglutinin is detected as multiple bands, electrophoretic mobility of most of them being lower than that of hemagglutinin of viral particles. This heterogeneity failed to be detected during electrophoresis under reducing conditions which is indicative of the differences in the number or direction of intramolecular disulfide bonds between short-labeled and mature hemagglutinin molecules. After chasing at 37 or 20 degrees hemagglutinin gradually assumes an electrophoretic character identical to that of virion protein. Chasing at 0 degrees or the substitution of parafluorophenyl alanine for phenylalanine in the maintenance medium during labeling prevents maturation. At the same time, both iodacetamide perfusion of infected cells and the preparation of nuclei-free extract prior to SDS lysis result in a marked increase in the yield of disulfide mature short-labeled hemagglutinin. These results suggest that disulfide maturation in hemagglutinin proceeds in two stages: a relatively rapid (with respect to synthesis completion) formation of intramolecular disulfide bonds as such followed by a much slower consolidation of bridges against the action of endogenous cell reductants which activate during lysis. Consolidation may be caused by two factors: trimerization of hemagglutinin monomers or their covalent post-translational modifications. PMID- 2309440 TI - Nucleotide sequence analysis of the S genomic segment of Prospect Hill virus: comparison with the prototype Hantavirus. AB - The genomic S RNA segment of Prospect Hill virus (PHV), a member of the Hantavirus genus, was molecularly cloned and the nucleotide sequence of the cDNA determined. The PHV S RNA segment is 1675 nucleotides long. A long open reading frame was identified in the viral complementary-sense RNA that could encode a 433 amino acid (49K) nucleocapsid (N) protein. Comparison with the sequence of the related Hantavirus (Hantaan 76-118) S RNA segment indicated that there was 57% nucleotide sequence homology between the two S RNA segments. A higher degree of conservation in amino acid sequence homology (62%) was observed in the N proteins of these viruses. At the N-terminus 147 of 225 amino acids are homologous, while approximately 82% of the 124 amino acids at the C-terminus are homologous between the two N proteins. The longest stretch of homologous amino acid sequence is found in this region, and is 17 amino acids in length. Also, many of the differences in amino acid sequence between the two N proteins resulted from conservative substitutions. Hydropathy plots of the two N proteins also reveal many similarities including a conserved potential antigenic site. Unlike Hantaan virus, a second smaller overlapping open reading frame was observed in the viral complementary-sense RNA of PHV and could potentially encode a 90 amino acid (10.5K) protein. Our data indicate that the N proteins of PHV and Hantaan virus are closely related despite divergence in the nucleotide sequence of their S RNA segments. PMID- 2309441 TI - A 14,500 MW protein is coded by region E3 of group C human adenoviruses. AB - There is an ORF in the early region E3 transcription unit of human adenovirus 5 (Ad5) which could encode a protein of 14,500 MW (14.5K). This ORF is conserved in Ad5 and Ad2, both group C adenoviruses, and also in Ad3 and Ad7, both group B adenoviruses. To address whether the 14.5K protein is synthesized, we prepared antisera against synthetic peptides corresponding to residues 19-34 or 118-132 in the Ad5 version of 14.5K, and also against a TrpE-14.5K fusion protein expressed in Escherichia coli. These antisera immunoprecipitated the [35S]Met-labeled 14.5K protein from KB cells infected with rec700 (an Ad5-Ad2-Ad5 recombinant), Ad2, and a variety of E3 mutants. Mutants in the 14.5K ORF did not produce the 14.5K protein. The 14.5K is coded in large part, although probably not exclusively, by E3 mRNA f, as indicated by immunoprecipitation of 14.5K from cells infected with mutants that overproduce or underproduce mRNA f. The 14.5K migrated as five to six bands on SDS-PAGE after immunoprecipitation or Western blot, suggesting that it undergoes post-translational modification. Two bands of 14.5K were obtained by cell-free translation of 14.5K from mRNA purified by hybridization from infected cells. PMID- 2309442 TI - Susceptibility to virus infection of transgenic tobacco plants expressing structural and nonstructural genes of tobacco rattle virus. AB - Tobacco plants were transformed with the coat protein (CP) genes and several nonstructural genes of tobacco rattle virus (TRV) strains PLB and TCM. Accumulation of RNA transcripts from the integrated viral genes was detectable in all types of transformants. Plants expressing CP were resistant to infection with virions of the homologous strain but susceptible to infection with RNA of the homologous strain or nucleoprotein of the heterologous strain. No resistance was detectable in plants transformed with the nonstructural 13K and 16K genes of strain PLB, or with the 29K gene that is unique to RNA-2 of strain TCM. When protoplasts from plants expressing TCM-CP were inoculated with TCM virions, there was a normal production of genomic RNAs and CP but the synthesis of mRNA and protein corresponding to the 16K gene was selectively defective. Because this defect was not observed when protoplasts from plants expressing PLB-CP were inoculated with PLB virions, it probably plays no role in the coat protein mediated protection observed in transgenic plants. PMID- 2309443 TI - The role of the viroid central conserved region in cDNA infectivity. AB - The effect of sequence duplication upon the infectivity of plasmid DNAs containing monomeric tomato apical stunt viroid cDNAs has been determined. Two factors appear to control the specific infectivity of the different plasmid constructions tested: the presence of a subset of a palindromic sequence located within the central conserved region and the orientation of the viroid cDNA within the recombinant plasmid. Deletions which disrupt the integrity of the putative processing site abolished cDNA infectivity, a result that is consistent with the involvement of this site in the cleavage/ligation of viroid RNAs during replication. PMID- 2309444 TI - Construction of novel viroid chimeras containing portions of tomato apical stunt and citrus exocortis viroids. AB - Several novel tomato apical stunt viroid (TASV) recombinants were isolated after inoculation of tomato seedlings with monomeric viroid cDNAs. Two intraspecific recombinants were constructed by exchanging the left and right sides of the closely related Ivory Coast and Indonesian strains of TASV, and a third, interspecific, recombinant was constructed by similar manipulations involving TASV and citrus exocortis viroid (CEV) cDNAs. Characterization of these TASV recombinants by RNA protection assays and nucleotide sequence analysis of polymerase chain reaction-amplified cDNAs revealed no evidence for sequence instability. The symptoms induced by replication of the CEV-TASV chimera in tomato were milder than those induced by either TASV or the TASV chimeras and resembled those induced by the CEV isolate which provided its pathogenicity domain. PMID- 2309446 TI - African swine fever virus: purification of capsomeres released by lipase. AB - The virus capsomeres of the outer and inner layers of capsids were effectively released simultaneously from purified virions by lipase digestion and were purified by a linear gradient ultracentrifugation. The capsid consisted of an array of double layers of uniformly arranged individual capsomeres where a lipid(s) served as a matrix in between the capsomeres. PMID- 2309445 TI - Intracellular processing, glycosylation, and cell-surface expression of the measles virus fusion protein (F) encoded by a recombinant adenovirus. AB - The membrane fusion protein of measles virus (MVF) is a surface glycoprotein which is essential for initiation of viral infection. The F protein mediates penetration of the host cell through a process of membrane fusion between the viral envelope and the host cell plasma membrane. To study the structure-function relationship of the MVF protein, a recombinant adenovirus, Ad5MVF, was constructed which expressed the F protein in mammalian cells. The MVF gene was inserted into the Ad5 genome by homologous recombination, which resulted in replacement of most of the E1 region. This recombinant virus was stable and replicated efficiently in the 293 cell line which complemented the deleted E1 functions. Human 293 cells infected with Ad5MVF synthesized an authentic MVF protein precursor (F0) which appeared to be cleaved efficiently to the F1 and F2 polypeptides. This recombinant F protein was glycosylated, transported to the cell surface, and found to be capable of inducing syncytia formation and hemolysis of monkey erythrocytes. The hemagglutinin protein (HA), provided by a coinfecting adenovirus, was not able to increase the biological activity of the F protein. Treatment of MV or Ad5MVF-infected cells with tunicamycin, an inhibitor of N-linked glycosylation, abolished processing of the F protein. This observation suggests that glycosylation might play an important role in cleavage dependent activation of the precursor F0 protein or in its transport to the subcellular region where proteolytic cleavage occurs. PMID- 2309447 TI - Site-directed mutations in the Sindbis virus 6K protein reveal sites for fatty acylation and the underacylated protein affects virus release and virion structure. AB - A small hydrophobic polypeptide of 55 amino acids, noted as the 6K protein, is formed during processing of the polyprotein translated from the Sindbis virus subgenomic 26 S mRNA. In the accompanying paper we show that this 6K protein can be found in purified preparations of virions and that it is palmitoylated via thioester bonds with about four covalently bound fatty acids per molecule. To determine acylation sites on 6K and define a role for these fatty acids, we used site-directed mutagenesis to alter cysteine codons in the 6K gene of Sindbis virus cDNA. One of these mutants had a single cysteine replaced with a serine and the second had two adjacent cysteines replaced with an alanine-serine sequence. Transfection of the transcribed RNA from these two cDNAs produced infectious virus which contained 6K proteins that had decreased amounts of fatty acids. Intracellular formation and maturation of virus glycoproteins appeared to be unaffected by the mutations but the release of virus particles from mutant infected cells was decreased about 70 to 90% from that observed with wild-type virus. Electron microscopy of virus-infected cells and of isolated virions showed that the 6K mutations led to large numbers of aberrant enveloped particles containing multiple nucleocapsids. These results indicate that the 6K protein and its state of acylation are important factors in Sindbis virus assembly and budding. Additional phenotypic changes are reported for virions released from cells infected with the mutationally altered viruses. PMID- 2309448 TI - Replication, stability, and gene expression of tobacco mosaic virus mutants with a second 30K ORF. AB - A series of tobacco mosaic virus (TMV)-hybrids containing a second 30K open reading frame (ORF) inserted into different positions of the genome 3' region were constructed. These insertional mutants were used to evaluate the effects of a modified viral genome organization on replication and gene expression. They were evaluated for stability upon systemic infection and subsequent host passage using RNase protection assays. A mutant with the second 30K ORF fused in frame to two-thirds of the coat protein reading frame replicated as a free-RNA virus and produced increased amounts of the hybrid protein compared to the wild-type 30K protein, but substantially reduced amounts compared to the wild-type coat protein. A mutant with the second 30K ORF inserted between the native 30K and coat protein ORFs produced reduced amounts of 30K protein but replicated efficiently and was maintained for weeks of systemic infection before the population gradually shifted to progeny wild-type TMV. Mutants with the second 30K ORF fused behind different lengths of the coat protein subgenomic RNA promoter/leader region and inserted between the coat protein gene and the 3' nontranslated sequences replicated poorly and the mutations were not maintained during continued replication in plants. PMID- 2309449 TI - Molecular cloning of the rinderpest virus matrix gene: comparative sequence analysis with other paramyxoviruses. AB - The nucleotide sequence of the gene encoding the matrix or membrane (M) protein of the virulent (Kabete-O) strain of rinderpest virus (RPV) has been determined. The M gene is 1457 nucleotides long with a single, large open reading frame. The derived polypeptide has 335 amino acids, corresponding to a calculated molecular weight of 38,289 and contains both small hydrophobic regions and many basic residues. The predicted amino acid sequence was compared to the M proteins of paramyxoviruses. Sequence comparison and hydropathy profiles among the morbilliviruses revealed that the M protein of RPV exhibits features similar to those of the M protein of MV and CDV. There is 78.2% homology at the amino acid level between the M protein of RPV and MV, and 77.6% between RPV and CDV. This indicates that a high degree of homology exists among the members of the genus Morbillivirus. In contrast, there is only 37.3 and 18% homology between RPV and bovine parainfluenza type 3 (BPV3), and RPV and Newcastle disease virus (NDV) M proteins, respectively. Thus the M proteins of the morbilliviruses are highly conserved whereas the M proteins of the genus Paramyxovirus show more divergence. PMID- 2309450 TI - Antigenic and genetic characterization of Sindbis virus monoclonal antibody escape mutants which define a pathogenesis domain on glycoprotein E2. AB - The Sindbis virus mutant SB-RL, in contrast to its parent, Sindbis strain AR339 (SB), is attenuated in neonatal mice, has an increased rate of penetration in tissue culture cells, and is more sensitive to neutralization by E2-specific monoclonal antibodies (MCAbs) R6 and R13. These phenotypic differences are controlled by substitution of an arginine for serine at amino acid 114 of the E2 glycoprotein. To explore these relationships further, MCAb R6 and R13 neutralization escape mutants of both SB and SB-RL were isolated and characterized. All mutants bound both MCAb R6 and R13 significantly less effectively in ELISA, and were more resistant to complement-mediated neutralization than their respective parental strains. Single coding changes in the E2 glycoprotein gene of each 11 mutants were identified. SB/R6, SB/R13, and SB-RL/R13 mutants contained a mutation at either E2 codon 96 or 159. SB-RL/R6 mutants contained changes at E2 codon 62, 96, or 159. These coding changes included two intragenic suppressor mutations. Mutation of E2 codon 159 from lysine to glutamate or codon 62 from asparagine to aspartate suppressed the attenuated phenotype conferred by E2 arginine 114 in SB-RL. However, only the change at E2 codon 62 significantly suppressed the rapid penetration phenotype of SB-RL. Mutation in E2 codon 96 of SB, replacing tyrosine with histidine, reduced the virulence of SB for neonatal mice but had no effect on penetration of cultured cells. Therefore, mutation in E2 codons 62, 96, 114, or 159 affected both virulence in animals and the binding or biological activity of these E2c specific MCAbs. These results suggest that an E2 antigenic site (E2c), defined by MCAbs R6 and R13, is conformational in nature and may constitute a surface domain on Sindbis virions important for virulence in neonatal mice. PMID- 2309451 TI - Characterization of the 5' and 3' ends of viral messenger RNAs isolated from BHK21 cells infected with Germiston virus (Bunyavirus). AB - The 3' ends of the S and M messenger RNAs isolated from BHK21 cells infected with Germiston virus were analyzed by mapping with RNase T2 or nuclease S1. The transcription termination signal was found to be located approximately 115 and 80 nucleotides upstream from the 3' end of the S and M genomic RNA templates, respectively. Both mRNAs were found to possess several adenosine residues at their 3' ends, but were not polyadenylated. They have acquired at their 5' end a heterologous 12- to 18-nucleotide-long sequence, which is not coded for by the virus. Sequencing of the 5' terminal region from single molecules cloned into pBR327 revealed that these primers are rich in C and G residues and possess a U or a C adjacent to the viral sequence. PMID- 2309452 TI - Cocirculation of two distinct evolutionary lineages of influenza type B virus since 1983. AB - During 1988-1989 two highly distinct antigenic variants of influenza type B were recognized in hemagglutination-inhibition tests with postinfection ferret serum. These viruses were antigenically related to either B/Victoria/2/87, the most recent reference strain, or B/Yamagata/16/88, a variant that was isolated in Japan in May 1988. All influenza B viruses isolated in the United States during an epidemic in the winter of 1988-1989 were antigenically related to B/Victoria/2/87. However, in several countries in Asia, both B/Victoria/2/87-like viruses and B/Yamagata/16/88-like viruses were isolated. Sequence analysis of the hemagglutinin (HA) genes of several influenza B isolates from 1987 to 1988 indicated that the HA1 domains of the B/Yamagata/16/88-like viruses and B/VI/87 like viruses isolated in 1988 differed by 27 amino acids. Evolutionary relationships based on this sequence data indicated that the B/Yamagata/16/88 like viruses were more closely related to epidemic viruses from 1983 (B/USSR/100/83-like viruses) than to more recent reference strains such as B/Victoria/2/87. All other Asian strains, as well as selected isolates from the United States in 1988, were confirmed by sequence analysis as being genetically related to B/Victoria/2/87. These data provide clear evidence that two parallel evolutionary pathways of influenza type B have existed since at least 1983 and that viruses from each of the separate lineages were isolated from cases of influenza B in 1988. This finding is similar to earlier observations for type A H1N1 and H3N2 influenza viruses. PMID- 2309453 TI - Transcription of orthopoxvirus telomeres at late times during infection. AB - The telomeres of orthopoxvirus DNAs consists largely of short repeated sequences organized into at least two separate sets. Although the sequence composition of the orthopoxvirus telomeres is highly conserved, these regions do not appear to encode any proteins. At late times during infection, the telomeres of vaccinia virus are transcribed. A promoter in the region between the two sets of repeats directs transcription towards the hairpin-loop end of the viral DNA. This promoter resembles the promoters of other poxvirus late genes, and directs the synthesis of RNAs whose structure is consistent with the presence of 5' poly(A) sequences typical of late RNAs. The lengths of these late transcripts suggest that some transcription extends through the hairpin-loop region. This might occur either when the genome is in a monomeric form or when the genome is in the concatemeric form of the DNA replication intermediate. The function of late transcription of the telomeres is unclear, but similar transcription of the telomeres of vaccinia virus, cowpox virus, and raccoonpox virus suggests that such transcription may have a role in viral replication. PMID- 2309454 TI - The optical transverse chromatic aberration on the fovea of the human eye. AB - The horizontal component of optical transverse chromatic aberration (TCA) at the fovea between 486 and 656 nm is measured in a sample of 8 eyes by two novel methods, both using vernier adjustment tasks with a retinal illumination of approx. 780 td and for a pupil size of approximately 5.5 mm dia. Initially, in an indirect method, TCA is derived along the line of sight from chromatic parallax. Secondly, TCA is measured directly using a semi-Maxwellian view and compensating for longitudinal chromatic aberration (LCA). Both techniques are unaffected by coma or by the Stiles-Crawford effects, thus optical TCA rather than the TCA perceived in normal view is measured. On average, optical TCA is in the same direction but less than previously predicted by eye models and predictions of the optical quality of the eye in white light are modified. Factors underlying the lower average value of optical TCA and variability among subjects, especially pupil centration and foveal position, are discussed. The relationship of optical TCA to TCA perceived in normal view and to chromostereopsis is analysed. The results suggest that the optical design of the human eye is optimized to reduce the wavelength dependent phase shift in the optical transfer function, which could be produced by optical TCA. PMID- 2309455 TI - A late receptor dystrophy in the Labrador retriever. AB - Dark adapted single flash and light adapted 30 Hz photopic flicker ERGs were recorded from a litter of seven Labrador Retrievers bred from parents affected with generalized progressive rod-cone dystrophy. After an initial increase of b wave amplitudes from 5 weeks to 4 months similar to the controls, the b-wave amplitudes of the litter were significantly decreased (P less than 0.005) at 7 months. At 21 months the b-wave amplitudes were very low, although some response to 30 Hz photopic flicker was still left. The ERG changes indicated a late onset progressive rod-cone dystrophy which developed after maturation of the retina. The development of this photoreceptor dystrophy has not previously been described. PMID- 2309456 TI - Distributions of choline acetyltransferase and acetylcholinesterase activities in the retinal layers of pigeon red and yellow fields. AB - The activities of choline acetyltransferase and acetylcholinesterase were assayed in submicrogram samples from layers of pigeon retina. Red and yellow fields were sampled separately to investigate quantitatively the relationship between these enzymes of acetylcholine metabolism and the gradient of inner plexiform layer complexity, increasing from the yellow field to the red. Choline acetyltransferase and acetylcholinesterase activities were concentrated in and near the inner plexiform layer, within which two peaks of activity for each enzyme were obtained. The distributions of enzyme activities indicate that populations of amacrine cells in the pigeon retina are cholinergic. The quantitative similarities between the enzyme activities in red and yellow fields suggest that the cholinergic system may not be specifically involved in the increase in inner plexiform layer complexity across the pigeon retina. PMID- 2309457 TI - The visual pigment basis for cone polymorphism in the guppy, Poecilia reticulata. AB - Long-wavelength visual pigment polymorphism, similar to that found in primates, was found in the guppy using microspectrophotometry (MSP). Guppies have a rod pigment with a wavelength of maximal absorbance (lambda max) at 501 nm and cone pigments with peak absorbance at 408 and 464 nm. In addition individuals may have one, two or three cone classes in the yellow-green region of the spectrum with mean lambda max values of 533, 543 and 572 nm. Unlike primates this variation is not sex-linked and may be based on only two visual pigments which occur either on their own in outer-segments of the 533 nm and 572 nm cone classes or as a mixture in the 543 nm cone class. PMID- 2309458 TI - Responses of visual cortical neurons to curved stimuli and chevrons. AB - Single cells were recorded in area 17 of anaesthetized and paralyzed cats and their responses to curved stimuli and chevrons compared. Striate cells exhibited three different response patterns. A first group responded optimally to a straight line (i.e. zero curvature) and responded similarly to chevrons and to curved lines. A second group responded to all curvatures and was broadly tuned for the straight line when tested with chevrons. A third group responded only to large curvatures, many (2/3) to both signs of curvature and a number (1/3) to only one sign. Cells in this group responded differently to chevrons and curved lines. Cells in these three classes differed both in length-response curve and in width of orientation tuning. Laminar analysis revealed that the three classes are distributed differently across cortical layers. These data shed new light on the finding of Malpeli and coworkers that orientation is extracted at least twice in a cortical column. PMID- 2309459 TI - The two-dimensional spatial structure of nonlinear subunits in the receptive fields of complex cells. AB - We have estimated the second-order response properties of complex cells in two spatial dimensions by cross-correlating their spike trains with a binary approximation of a Gaussian white noise stimulus ensemble. Wiener-like kernels were computed and generally consisted of two or three parallel, elongated subregions alternating between augmented and suppressed response. These subunits were scattered across the receptive fields of complex cells and their axes of elongation agreed with the optimal orientation determined with drifting gratings. PMID- 2309460 TI - Evaluation of retinal orientation and gaze direction in the perception of the vertical. AB - The orientation of the median plane of the eye with respect to the head varies with gaze direction according to Listing's Law. The subjective vertical (SV), however, is known to be only partially affected by these involuntary variations of eye orientation. In order to learn more about the compensatory process underlying this finding, six normal-sighted young subjects were tested monocularly and binocularly in eight directions of gaze. The results show that: (1) the SVs, determined monocularly for both eyes, fall on corresponding retinal meridians, the binocular SV-settings generally lie between the monocular ones; (2) the tilt of the SV is not linearly related to the tilt angle of the median plane of the eye, as hitherto assumed. On theoretical considerations, the dependence of ocular tilt on gaze direction may be decomposed into three components, which are all treated differently in the compensation process. We interpret these results in the following way: the SV is determined from the sensorially fused image of both eyes and the tilts of the eyes are accounted for by an extra-retinal signal which is common to both eyes. The characteristics of the compensation mechanism may be explained by an extra-retinal signal which relies on information about gaze direction and Listing's Law. Such a signal might be derived from an efference copy of gaze direction commands. PMID- 2309461 TI - Spatial-filter selection in large-scale spatial-interval discrimination. AB - Spatial-interval discrimination thresholds were measured for a pair of bars in the presence of other parallel bars placed far enough from the targets as to be outside the range of neural and optical blurring. Thresholds were elevated when the targets were embedded in an array of four parallel bars (two between and two flanking the targets), but not when there were only two parallels, whether the parallels were between the target bars or flanking them. The threshold elevation was larger with a 100-msec than with a 500-msec exposure duration. Attenuating the high spatial frequencies magnified the threshold elevation. The data indicate that the process responsible for spatial-interval discrimination automatically selects which spatial filters to use; it does not have to scan through all ranges of spatial filters. PMID- 2309462 TI - Perceived direction of moving two-dimensional patterns. AB - When two drifting cosine gratings are superimposed, they will, under appropriate conditions, form a coherently moving two-dimensional pattern whose resultant direction of motion may either be between (type I), or outside (type II) the directions of the two components. We have previously shown that type I patterns produce much stronger masking than either of their components, while type II patterns do not. In this study, we measured perceived direction of motion and thresholds for discrimination of motion direction. We found that type II patterns had a perceived bias of about 7.5 deg toward the direction of their components, and had discrimination thresholds around 6.5 deg, whereas type I patterns had discrimination thresholds around 1.0 deg and no significant bias. We conclude that the neural mechanisms which compute two-dimensional image motion do not strictly implement the intersection-of-constraints construction proposed by Adelson and Movshon (1982). PMID- 2309463 TI - Motion mechanisms have only limited access to form information. AB - We investigate the roles of spatial frequency content, flicker and higher-order elements of form ("features") in the generation of motion percepts. These cues are separated through the use of dynamic visual stimuli based on stochastic textures. Flicker alone and spatial frequency content alone suffice to generate a strong motion percept, but higher-order elements of form alone generate a much weaker motion percept. Thus, even for achromatic stimuli, all pattern information is not equally available for motion processing. Furthermore, higher-order form information, which by itself does not provide a strong cue to motion, is shown to interact with other visual information to facilitate determination of direction of motion. PMID- 2309464 TI - Direction discrimination for band-pass filtered random dot kinematograms. AB - When an array of random dots is displaced, the ability to report the direction of apparent motion is subject to an upper spatial limit (dmax). As the size of the displacement is increased, direction discrimination errors show a monotonic increase that becomes asymptotic at a chance level. We have measured direction discrimination using spatially band-pass filtered random dots. These stimuli do not yield a monotonic increase in errors. Rather, for displacements greater than around 1 cycle of the stimulus centre frequency (Fc), performance oscillates about chance, with displacements of 1 1/4 cycles of Fc yielding systematic errors in perceived direction. We analyse this pattern of performance in terms of the stimulus autocorrelation function and conclude that dmax can be taken as lying on the initial rising portion of the displacement versus error function. Using this definition we find, in line with the results of Chang and Julesz (1985), that dmax scales inversely with Fc. Contrary to the results of Chang and Julesz, we find that this scaling holds beyond 4 c/deg. PMID- 2309465 TI - Masking of low frequency information in short-range apparent motion. AB - When an array of random dots is displaced, the ability to report the direction of apparent motion is subject to an upper spatial limit (dmax). Using spatially low pass filtered random dot kinematograms we show that dmax is dependent on the upper cut-off frequency of the stimulus (Fh). The extent of this dependence is critically dependent on the size of the stimulus. Our results suggest a process whereby low spatial frequency motion information is masked by the presence of high spatial frequencies in the same region of the field, analogous to phenomena occurring in the perception of static form (e.g. the Abraham Lincoln effect). The effects of stimulus size on dmax, found for broad-band stimuli by ourselves and others, result from a loss of high frequency sensitivity at increased retinal eccentricities; this loss reduces the masking effect of high frequencies, as stimulus size increases. PMID- 2309466 TI - Applications of the EVE software for visual modeling. AB - EVE, the Early Vision Emulation software, is a system for the stimulation of early visual processing. EVE has the ability to carry out the operations of a wide variety of models of spatial vision, motion detection and processing, and spatial sampling. We introduce the EVE software and illustrate some of its applications for models of pattern detection, pattern discrimination, and motion detection. PMID- 2309467 TI - Health of black and white Americans, 1985-87. PMID- 2309468 TI - Giant single anastomotic aneurysm arising from both iliac limbs of an aorto-bi iliac reconstruction. AB - Anastomotic aneurysms can occur at all sites of arterial revascularization. Recurrent aneurysmal disease, both true and anastomotic, is the third leading cause of late mortality after aortic aneurysm resection behind coronary artery disease and neoplastic disease (8). For this reason, long-term follow-up after resection is mandatory. If an anastomotic aneurysm is found at one site, a search should be undertaken at other sites. If a heretofore unrecognized intraabdominal anastomotic aneurysm is found, it should be repaired promptly. PMID- 2309469 TI - Alzheimer's disease as a diagnosis of exclusion. AB - Although dementia is frequent among the elderly, and usually the result of Alzheimer's disease, other illnesses may be responsible. A diagnostic approach to discover such treatable disorders is detailed in this paper. PMID- 2309470 TI - Your responses pour in. PMID- 2309472 TI - Best interest of dying patient. PMID- 2309471 TI - Foreign example. PMID- 2309473 TI - N-of-1 clinical trials. A technique for improving medical therapeutics. AB - This discussion was selected from the weekly Grand Rounds in the Department of Medicine, University of Washington School of Medicine, Seattle. Taken from a transcription, it has been edited by Paul G. Ramsey, MD, Associate Professor of Medicine, and Philip J. Fialkow, MD, Professor and Chair of the Department of Medicine. PMID- 2309475 TI - N-of-1 randomized trials--where do we stand? PMID- 2309474 TI - Physician risk and responsibility in the HIV epidemic. AB - These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Homer A. Boushey, MD, Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143. PMID- 2309476 TI - Are vitamin A supplements needed during pregnancy? PMID- 2309477 TI - Health care--where are the problems and where are the solutions? PMID- 2309478 TI - Neonatal cardiac allotransplantation facilitated by in utero diagnosis of hypoplastic left-sided heart syndrome. The Loma Linda University Heart Transplant Group. PMID- 2309479 TI - Carcinoid tumors of the thymus. PMID- 2309480 TI - Confidential versus anonymous human immunodeficiency virus antibody testing. PMID- 2309481 TI - The cost of medicine. PMID- 2309482 TI - Alopecia universalis in autoimmune polyglandular syndrome type I. PMID- 2309483 TI - Dialysis disequilibrium syndrome. PMID- 2309484 TI - Electroconvulsive therapy use during pregnancy. PMID- 2309485 TI - Vitamin A--a pregnancy hazard alert. AB - Vitamin A is essential to human health, but concerns have arisen recently regarding its potential teratogenicity. Human and animal birth defects have been associated with the use of the vitamin A analogue, isotretinoin, or Accutane, for acne treatment, although the association of such defects with vitamin A itself is unclear. The federal Food and Drug Administration is evaluating the health issues surrounding vitamin A and, together with the manufacturer, has developed restrictions and label warnings to ensure the appropriate use of Accutane. We also have evaluated these issues, with concerns about the possible teratogenicity of high vitamin A intake during pregnancy. Practitioners should be familiar with the possible hazard of excessive dosages of vitamin A and its analogues. Vitamin A daily doses of higher than 8,000 IU for pregnant woman are not necessary for good health and are not recommended. Foods high in beta-carotene can provide the necessary amounts of vitamin A and, in contrast to the synthetic analogues, their use has not been associated with vitamin A toxicity or teratogenicity in humans or animals. PMID- 2309486 TI - Sleep deprivation and cognitive testing in internal medicine house staff. AB - There is increased concern about the effects of sleep deprivation on physician performance. We administered four standard tests of cognitive function to 23 university hospital house staff. Each physician served as his or her own control, and the tests were administered at rest, after a night on call, and after a night of sleep for recovery. The study was designed so that normal learning would minimize any deterioration in the post-on-call test performance. Statistically significant deterioration occurred in 3 of the 4 tests after a night on call. Even physicians acclimated to sleep deprivation on a regular, every-third-or fourth-night basis showed functional impairment. The results have implications for patient care under conditions where house staff are stressed by sleep deprivation and prolonged fatigue. PMID- 2309488 TI - After shock. PMID- 2309487 TI - Perceived health quackery use among patients. A physician survey. PMID- 2309489 TI - Left hilar mass without pulmonary disease. Pulmonary artery aneurysm. PMID- 2309490 TI - Who are you? PMID- 2309491 TI - [Steroid therapy in subarachnoid hemorrhage]. AB - Increase in intracranial pressure due to brain oedema is one of the most frequent complications of subarachnoid hemorrhage (SAH), apart from vasospasm and hydrocephalus. Up to now the administration of corticosteroids at various dosages has been the standard therapy for brain oedema. With this retrospective study we tried to answer the question whether the administration of dexamethasone at high dosage in patients with SAH bears an increased risk of medical complications such as infections, gastrointestinal bleeding and diabetes mellitus. 171 consecutive patients of our intensive care unit, 51 men and 120 women (average age 52.4 +/- 13.6 years) were included in the study. 107 patients received dexamethasone in high doses according to Gobiet's scheme. 64 patients who were not given any steroids formed the control group. Almost the same frequency of gastrointestinal bleeding was registered in the steroid group (2.8%) and in the control group (3.1%). No increase in diabetic problems was found in the steroid group, either. The steroid group showed an increase in infections (38.3% compared with 28.1% in the control group; p less than 0.001). The increase, however, was entirely due to the more frequent occurrence of urinary tract infections (14.0% vs. 4.7%). Dexamethasone therapy at high dosage bears no increased risk of medical problems in patients with SAH, except for a greater number of urinary tract infections. However, stomach ulcer prophylaxis and monitoring of blood sugar levels and electrolytes are deemed necessary. PMID- 2309492 TI - [HIV infection and AIDS in Austria]. AB - AIDS is a notifiable disease in Austria. Until August 31, 1989, a total of 324 cases were recorded, with 145 deaths. Since 1988, the annual doubling of cases that was initially found is no longer observed. Centralization of confirmatory testing of samples that are positive in the ELISA permits us to follow up the incidence and prevalence of HIV infections. By September 15, 1989, a total of 3,071 persons were found to be infected. The highest rates of AIDS patients and seropositive individuals were recorded in Vienna (151/1,712), followed by Upper Austria (63/606) and the Tyrol (29/367). Among those found to be positive since October 1987, 28% are homo- or bisexual and 42% are i.v. drug addicts. About 4% of men and women report heterosexual contacts as the likely mode of infection. Since 1986 the yearly incidence of HIV infection appears to be decreasing. This development corresponds with a decline in other sexually transmitted diseases (gonorrhoea, hepatitis B) and indicates a change in the sexual behaviour of the population. PMID- 2309493 TI - Personal health practices. PMID- 2309494 TI - The eating patterns and problems of homeless women. AB - While inadequate nutrition has been identified as a factor affecting the health of the homeless, there has been little research to identify the extent to which inadequate nutrition is a problem. The goal of this paper is to document the eating patterns and problems of single homeless women and to locate the determinants of nutritional adequacy in their diets. Our findings are based on a random sample of 84 single homeless women using hostels and drop-in centers. For 85.5% of the women food was provided primarily by hostels and supplemented by the drop-ins. When their daily food intake was compared to the Canada's Food Guide recommendations, the average number of servings in each of the four food groups was below the recommended. The women in our sample indicated that their problems with food consumption were rooted in their poverty and further analysis indicated that the provision of food by social agencies was an important factor in the nutritional adequacy of their diets. Hostels and drop-in centers not only provide shelter, they have also assumed most of the responsibility for feeding the homeless. It is their poverty which burdens these women and structures their eating patterns. PMID- 2309495 TI - A causal analysis of employment and health in midlife women. AB - According to the "healthy worker" hypothesis, good health selects women into the employment role; conversely, the social causation hypothesis argues that important social roles such as employment can contribute to health. The relationship between these two variables may be of special concern to women at midlife, as both issues become increasingly salient. In this paper a model hypothesizing a nonrecursive (reciprocal) causal relationship between employment (hours employed) and health was presented. Because of the importance of both employment and health for women at midlife, the model was tested in a sample of 463 women ages 40-64 from a national cross-sectional dataset. Two-stage least squares regression supported the hypothesis that employment and health have a positive reciprocal relationship for women at midlife. In addition, married women and those with a child had better health but were likely to work fewer hours for pay. The same model tested in 21 to 39-year-old women was not significant. The results serve to emphasize the importance of examining assumptions about direction of causality in research on work and well-being at midlife. PMID- 2309496 TI - Religious influence on menstrual attitudes and symptoms. AB - Menstrual attitudes and symptoms of 18 Orthodox Jewish Mikvah attenders, 23 Orthodox Jewish Mikvah non-attenders, 35 Protestant women, and 45 Catholic women were compared. When age, education, number of pregnancies, and religiosity were controlled, Mikvah non-attenders and Protestants most strongly endorsed a view of menstruation as a bothersome event. No significant differences were found, however, in expected or retrospectively reported menstrual symptoms. Correlational analyses indicated that attitudes, expectancies, and symptoms were significantly correlated only for the Catholic women. Differences between groups in religiosity and socialization were found. The Jewish women endorsed doctrines such as "menstruation makes women unclean" more than Catholic or Protestant women. Results support the hypothesized differential religious training regarding menstruation, but only offer weak support for the effects of this training on menstrual attitudes, expectancies, and symptoms. PMID- 2309497 TI - Dioxin levels in adipose tissues of hospitalized women living in the south of Vietnam in 1984-89 with a brief review of their clinical histories. AB - Agent Orange, a phenoxyherbicide consisting of 50% 2,4-D and 50% 2,4,5-T, the latter contaminated in the parts per million range with the highly toxic dioxin, 2,3,7,8-TCDD, was sprayed in the south of Vietnam from 1962 to 1971. The chemicals are of concern because of their potential to be causally involved in cancer, adverse reproductive outcomes, immune deficiency and other illness. Because exposed women would be especially involved in the adverse reproductive outcomes, specifically spontaneous abortions and congenital malformations, as well as developmental deficiencies in children, we elected to conduct a pilot study in Vietnam to determine whether elevated 2,3,7,8-tetrachloro-p-dioxin (TCDD), the dioxin characteristic of Agent Orange could still be found in some women between one and two decades after exposure, and whether the types of illness characteristic of dioxins was present in women with elevated dioxin levels. We were easily able to find some women with increased TCDD from Agent Orange, A surprisingly high level of dioxins from industrial sources was also found in these women in the south. Much lower levels of all dioxins were found in patients in the north of Vietnam. No obvious relation between elevated dioxins and disease was noted in this pilot study, which is meant to precede epidemiology studies which will test the hypotheses that elevated dioxins in humans may lead to an increase in adverse reproductive outcomes and in rates of certain cancers. PMID- 2309498 TI - Fake abortion clinics: the threat to reproductive self-determination. AB - The establishment of "fake abortion clinics" poses a great threat to women's ability to make free and informed procreative decisions. Such clinics intentionally deceive pregnant women into believing that they provide a full range of women's health services when, in reality, they provide only a pregnancy test, accompanied by intense anti-abortion propaganda. Because fake abortion clinics threaten women's interests in "privacy" and decisional autonomy, state attorneys general should challenge them under deceptive business practice statutes. Successful challenges can be brought without violating anti-abortion groups' First Amendment rights. PMID- 2309499 TI - Arbitration as an alternative to torts. PMID- 2309500 TI - A victim of misinformation. PMID- 2309501 TI - The 80-hour work week revisited. PMID- 2309502 TI - Liver cancer in Wisconsin: the potential for prevention. AB - In this study liver cancer deaths that could be attributed to certain risk factors were calculated. Applying population attributable risk methodology, the attributable risk of liver cancer was estimated for alcohol use, hepatitis B viral exposure, and occupational and industrial exposures. We found that these three risk factors accounted for 38% of liver cancer mortality in Wisconsin; 29% was attributable to alcohol consumption, 7% to occupational exposures, and 2% to hepatitis B viral infection. More than half of liver cancer mortality, however, was not accounted for by the three risk factors studied. PMID- 2309503 TI - Cardiac involvement in metastatic breast cancer. AB - Metastatic disease is the most common cause of death in breast cancer. Although cardiac involvement has been reported in 12% to 30% of cases, intra-atrial involvement is rare. In this report we describe a 41-year-old woman with metastatic breast cancer whose left atrium was invaded by a metastatic tumor that resulted in intermittent left ventricular in-flow obstruction. Such a presentation has not been described previously in metastatic breast cancer. The pertinent literature is reviewed. PMID- 2309504 TI - Wisconsin's clean indoor air act. PMID- 2309505 TI - Aspects of food production, consumption and energy values. PMID- 2309506 TI - Lack of effect of piroxicam on theophylline clearance in healthy volunteers. AB - This study was conducted to determine if piroxicam alters the clearance or metabolism of theophylline in healthy adults. Six male volunteers were given aminophylline 6 mg/kg iv before and after piroxicam treatment. Piroxicam 20 mg/d po was administered for seven days. Serum samples were collected before and for 24 hours after each aminophylline dose. Theophylline serum concentrations were determined using the Abbott TDx automated immunoassay system. Theophylline and its 1,3-dimethyluric acid metabolite were measured in 24-hour urine collections. Serum theophylline concentration versus time curves were plotted and pharmacokinetic parameters determined for each subject. None of the derived parameters differed as a result of piroxicam exposure. Theophylline metabolites, clearance, half-life, and volume of distribution were compared during the baseline and piroxicam phases and were found to be similar. It was concluded that piroxicam does not alter the clearance, distribution, volume, or metabolism of theophylline in healthy adult volunteers. PMID- 2309507 TI - Prospective evaluation of liver function tests in patients treated with aminoglycosides. AB - We investigated the relationship between therapy with aminoglycoside antibiotics and alterations in serum liver enzymes and bilirubin. One hundred fourteen patients treated with aminoglycosides and 96 treated with other antibiotics were assessed prospectively during eight days. No elevation in serum alanine aminotransferase, lactic dehydrogenase, or bilirubin was detected in the aminoglycoside and control groups. Alkaline phosphatase increased significantly in the aminoglycoside group (average elevation of 28 +/- 16 units/L on day 6), but no patient had an elevation greater than twice the upper limit of the normal range. We conclude that the abnormality in liver enzymes during aminoglycoside therapy is a mild elevation in alkaline phosphatase, probably with no clinical significance. PMID- 2309508 TI - Potential neurologic toxicity related to ciprofloxacin. AB - A 74-year-old woman with multiple medical problems including chronic renal failure was admitted for treatment of a diabetic foot infection. On day 12 of therapy with oral ciprofloxacin and metronidazole, the patient experienced generalized myoclonus and muscle twitching. At that time it was realized that although the ciprofloxacin regimen prescribed was a usual dose for a skin and soft-tissue infection, it was excessive for her degree of renal function. This was thought to be the most likely cause of the patient's neurotoxicity. Seizure activity has been reported to occur with the quinolone antibiotics and, with the increasing use of these agents, dose reductions should be kept in mind to avoid potentially serious adverse reactions. PMID- 2309509 TI - Severe reversible thrombocytopenia resulting from butoconazole cream. AB - A 54-year-old woman with a 19-year history of rheumatoid arthritis developed life threatening thrombocytopenia one week after beginning butoconazole therapy for a vaginal yeast infection. This was complicated by upper gastrointestinal hemorrhage that probably resulted from ibuprofen and methotrexate therapy. Sepsis, myelophthisic anemias, and other potential etiologies were ruled out. Once stabilized, the patient was rechallenged with other medications without incident. These findings indicate that a potentially serious thrombocytopenia may result from the administration of butoconazole vaginal cream or in combination with methotrexate and/or ibuprofen. PMID- 2309510 TI - Hydrochlorothiazide dosage in hypertension. PMID- 2309511 TI - Topical aminocaproic acid in hemophiliac patients undergoing dental extraction. PMID- 2309512 TI - Pharmacotherapy. Part IV. The future of specialization and certification in pharmacy. PMID- 2309513 TI - Selecting cost-effective antimicrobial prophylaxis in surgery: are we getting what we pay for? AB - The acquisition, administration, and infection-related expenses associated with the use of cefazolin or cefamandole during a prospective randomized comparison of antimicrobial prophylaxis in cardiac surgery were compared. Although the acquisition cost and administration charges related to the use of cefamandole were in excess of those incurred with cefazolin, differences in the charges associated with treating the wound infections that failed prophylaxis with each regimen made cefamandole the more cost-effective prophylactic agent (mean total of $766 per cefazolin recipient vs. $315 per cefamandole recipient). Analysis of prophylactic antimicrobials should include the expenses associated with "prophylactic failures." The agent that is least expensive for the pharmacy may not be the most cost-effective choice for the institution. PMID- 2309515 TI - Nonthrombocytopenic purpura induced by cefoxitin. PMID- 2309514 TI - A team approach to reduce antibiotic costs. AB - After partial success in reducing antibiotic drug costs by traditional methods (i.e., closed formulary, use of generic drugs, retrospective drug usage review, continuing education), a study of a new "team approach" was implemented. The study involved a clinical pharmacist and physicians working together to select the most appropriate antibiotic therapy. The clinical pharmacist reviewed the culture and sensitivity data and the pattern of infectious disease over the six month period prior to the initiation of the study and prepared a list of the most appropriate antibiotics based on clinical efficacy and cost effectiveness. He then joined the physicians on morning rounds to monitor therapy and help in the selection of the most appropriate drug regimen. At the end of the study period, antibiotic cost savings of 58.6 percent were achieved. PMID- 2309516 TI - Drug utilization evaluation of cefotetan versus cefoxitin in large teaching hospital. PMID- 2309517 TI - Exacerbation of myasthenia gravis by norfloxacin. PMID- 2309518 TI - Clinical pharmacy as perceived by a foreign physician. PMID- 2309519 TI - Estimating pharmacokinetic values. PMID- 2309520 TI - Smoked tuna, sliced and vacuum packed, a relatively new product. AB - The possibility of storing vacuum packed, smoked and sliced tuna fish was studied. The microbiological and chemical analyses demonstrated that hygienic conditions and organoleptic properties remain unaltered after storage at 5 degrees C for 60 days. PMID- 2309521 TI - Separation of phospholipids in bovine tissue with disposable silica gel extraction columns. AB - A simple and elegant method using disposable silica gel columns has been developed to separate the phospholipid fraction in beef muscles from other fatty acid containing lipids. By this method, 10 samples can be cleaned up simultaneously in less than 2 h. It does not require complicated equipment. The separation of the phospholipid fraction is necessary in order to characterize it by chemical means, for instance to determine the fatty acid pattern. Recovery and reproducibility were proved with a model meat system. Purity was proved with a model system and biological samples. PMID- 2309522 TI - Methods for detection of irradiation of spices. AB - Three types of methods for the identification of irradiation of spices were tested as potential control methods. The methods were microbiological, combining a direct epifluorescent filter technique (DEFT) with a total aerobic plate count (APC), a chemiluminescence method and chemical gas-chromatographic (GC) and GC mass-spectrometric (MS) methods for analysis of volatile oils of spices isolated by steam distillation. Twelve samples of spices, mainly peppers, were analysed before and after gamma-irradiation with doses of 10 and 50 kGy. The chemiluminescence measurements were performed before the irradiation and 10 and 100 days after the irradiation. The best methods for control purposes were the microbiological (DEFT + APC) methods combined with chemiluminescence measurements. No differences were detected between the irradiated and non irradiated samples with the chemical methods. PMID- 2309523 TI - Projected impact of the trend toward delayed childbearing on breast cancer incidence in the Saarland/FRG. AB - The potential impact of the trend toward delayed childbearing or nulliparity on future breast cancer incidence is quantitatively assessed for the Saarland/FRG. Distribution of age at first birth is estimated from vital statistics for seven five-year birth cohorts from 1936-40 to 1966-70. Estimates of the relative risks associated with age at first birth or nulliparity are based on median results of 23 controlled epidemiologic studies conducted in Europe and North America. Compared to the birth cohorts around 1940, a steady increase in incidence up to about +15% is projected for the younger cohorts indicating a substantial public health impact. Using data of the population based cancer registry of the Saarland, the cumulative incidence of breast cancer up to age 50 is calculated as 1.52% for the 1936-40 birth cohort and is projected to rise to 1.75% in the 1966 70 cohort. Similar changes in fertility patterns have been observed in other parts of the FRG. Given the continuing rise in mortality from breast cancer in the FRG this stresses the need for more effective screening procedures. PMID- 2309524 TI - The effect of involuntary smoking on the occurrence of chronic obstructive pulmonary disease. AB - One hundred and three ever-married women with newly diagnosed Chronic Obstructive Pulmonary Disease (COPD), who have never smoked, and 179 ever-married women who were visiting friends or relatives at the same hospital during the same period and have never smoked, were interviewed regarding the smoking habits of their husbands. There was statistically marginally significant difference between the COPD cases and the controls with respect to their husband's smoking habits. The association was irregular with respect to daily number of cigarettes smoked but there was a smooth dose response curve with respect to life long total number of cigarettes smoked, with women whose husband smoked more than 300 thousand cigarettes having a relative risk of 1.8 (90% confidence interval of 0.9-3.6) compared to women whose husband has never smoked. These findings, and converging related evidence, indicate that exposure to environmental tobacco smoke may be a risk factor for the development of COPD. PMID- 2309525 TI - [Mortality analysis: when is single evaluation of the basic cause of death allowable, when should multi-causality be assessed?]. AB - Data quality is often a critical point in mortality studies. The purpose of the present report is to present criteria for assessing the value of death certificate-based mortality studies. For this purpose all 57,454 Swiss death certificates of the year 1979 were analysed. Reliability of the diagnosis listed on the death certificate was investigated by comparing for each case of a linked sample of 12,478 deaths the cause of death with medical information available from the hospital record. Retrieval rates (percentage of cases for which the given diagnosis appears in both registries) were calculated for the primary diagnoses named in each data set. These can be considered as measures of reliability of diagnoses. The graphs given indicate a high reliability for cancers and accidents. Reliability was lower for other causes of death such as cardiovascular diseases, diabetes mellitus, rheumatic diseases. Restriction to the primary cause of death can be accepted for most cancers, accidents and violent deaths. For other causes of death, decisions must be made individually and multicausal analysis may be indicated. In addition, knowledge of the reliability of the diagnoses of interest is necessary for the interpretation of results derived from death certificate-based mortality studies. PMID- 2309526 TI - [Patients in ambulatory care]. AB - A study on ambulatory medical care has been conducted in the cantons of Vaud and Fribourg in february-march 1987. The characteristics of patients visiting a private doctor and those of outpatients in hospitals are described. At private offices women older than 15 years consult more often than men; children (0-4 years) and elderly are the groups of population who consult most. In ambulatory services of hospitals, men are more present than women; children aged 0 to 4 years and adults aged 15 to 39 years use most these services. Use of ambulatory care varies with regions and days of the week. In urban regions, people have more medical visits. On Thursdays and weekends, there are less consultations but they are more often urgent. PMID- 2309527 TI - [Epidemiology of hypertension and hypercholesterolemia: results of a mass screening in the framework of "a week in Kiel" 1988]. AB - A screening for total cholesterol levels and blood pressure was conducted in Kiel during the sailing competition 1988 following the suggestion of the American Health Foundation. During the ten days of the testing 2063 visitors were screened, aged 5 to 88 years. Two thirds of the participants had no idea about the connection between high blood pressure, elevated cholesterol levels and the risk of coronary heart disease. The percentage of subjects with normotonic blood pressure decreased from 98 to 63% by age. Concerning the cholesterol levels the percentage of subjects at moderate risk for coronary heart disease increased from 20 to 80% by age and beyond fifty years of age the persons had cholesterol levels above 240 mg/dl. The total cholesterol levels increased by cigarette smoking. Our results demonstrate the need to improve the efforts of health education for lowering the cholesterol levels in the population, and thereby lead to a reduction in the morbidity and mortality of coronary artery disease. PMID- 2309528 TI - [Roentgenologic heart volume determination for the diagnosis of fatal heart failure]. AB - In order to investigate the connection between the cardiac volume and the cardiac shadow plane, 385 anterior-posterior radiographs of the thorax have been selected comparing their cardiac shadow plane with the corresponding cardiac volumes determined by the autopsy of the cadavers. The comparison showed a connection of both magnitudes by means of the formula Hvol = 0.49 x Fa x square root of Fa (Hvol = cardiac volume in cm3, Fa = cardiac shadow plane of the anterior posterior radiograph in cm2, corrections were made from the radiation divergence). A verification of the formula showed a very high correlation (r = 0.984) in 25 cadavers to be dissected. The comparing volume of the cardiac shadow plane has been investigated by means of the water displacement method, in which the cardiac vessels were ligated and the heart taken out of the cadaver. The cardiac volume, evaluated from the cardiac shadow plane showed a significant correlation at the cardiac death by internal natural cause. The comparison of the mathematical evaluated cardiac blood volumes of the symptoms causing death showed that the cardiac blood volumes in the group of poisonings and the group of drowning, suffocations and hanging with 231 ml and 211 ml in the men collective were at the same level as the cardiac death (246 ml). About the same applied to the women collective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309529 TI - Polymorphism of plasminogen in Tuscany (Italy). AB - The distribution of PLG phenotypes in the population of Tuscany (Central Italy) has been investigated by means of isoelectric focusing followed by immunofixation of desialyzed sera. In a random sample of 383 unrelated healthy blood donors registered at the Hospital of Pisa, three common phenotypes, PLG A, A-B, and B, and two rare variants were found. The allele frequencies calculated in our study were: PLG*A = 0.6749, PLG*B = 0.3225, and PLG*rare = 0.0026. The theoretical exclusion rate in cases of disputed paternity is 17.42%. PMID- 2309530 TI - [Resuscitation measures and petechial thymus hemorrhages in sudden infant death]. AB - In 45 cases of sudden infant death syndrome (SIDS) in which unsuccessful attempts at resuscitation had been made and in 21 cases without attempted resuscitation, systematic histological investigations were carried out on the thymus. In these investigations, petechial hemorrhages were detected in 82% of the cases with attempted resuscitation and in 76% of the cases without attempted resuscitation. The histological distribution pattern of the petechial thymus hemorrhages did not differ notably between the two groups. The pattern of findings indicates that the hemorrhages had already developed during the death agony and that the typical histological distribution pattern with an increased occurrence of petechial in the cortical zone was altered by massive attempts at resuscitation in individual cases. PMID- 2309531 TI - [Atypical ventricular septal defect]. AB - A case of a congenital cardiac malformation in form of a single ventricular septal defect is reported and histopathologic findings are presented. The possible origin with regard to its untypical localisation is discussed. PMID- 2309533 TI - [A heat gelatinized subdural hematoma in a burned cadaver as an indication of a vital accident]. AB - The autopsy of a carbonized male cadaver revealed a subdural hematoma which permitted by absence of soot aspiration and carbon monoxid intoxication to think of a crime with following fire setting. This was confirmed later by detective investigations. The most impressive finding of this case was a heat-gelatinized subdural hematoma highly resembling to a postmortem epidural burn hematoma, which could easily lead to an error conclusion. The problems in the diagnosis of the causes of death in carbonized bodies are discussed and the taking into account of crimes is accentuated. PMID- 2309532 TI - [Sudden infant death--fatal poisoning with pheniramine]. AB - A case of unintentional fatal intoxication of a 10 month-old baby with the anti histamine Pheniramine (Avil) is reported. On the face value and without an autopsy this case parallels familiar cases of SIDS and had for this reason been certified as such. Autopsy, however, revealed 32 partly dissolved tablets which proved to be Phenyramine. High concentrations of Pheniramine were found in body fluids and various tissues. According to official investigations, the tablets were offered to the baby by his 3 1/2 year old sister who probably believed they were sweets. PMID- 2309534 TI - [Comments on: "Determination of calcium and magnesium in postmortem human vitreous humor as a test to ascertain the cause and time of death" by R. Nowak and S. Balabanova]. PMID- 2309535 TI - Humanism in nursing science. PMID- 2309536 TI - Pain corner: back to the basics. PMID- 2309537 TI - Effects of thoracic epidural anaesthesia on central haemodynamics compared to cardiac beta adrenoceptor blockade in conscious rats with acute myocardial infarction. AB - The study aimed to compare the effects of thoracic epidural anaesthesia (TEA) with those of the beta-adrenoceptor blocker, metoprolol, on central haemodynamics in conscious rats with acute myocardial infarction. During methohexital anaesthesia, appropriate vascular catheters were inserted, a thoracic epidural catheter was implanted and the left coronary artery was ligated. A recovery period of 1-2 h elapsed after termination of surgery and anaesthesia. Experiments were performed on four separate groups of animals (A-D). In Group A (n = 10) mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO) were measured, and stroke volume (SV) and systemic vascular resistance (SVR) were calculated before and 10-15 min after the induction of TEA (bupivacaine 5 mg.ml-1). In Group B (n = 6) left ventricular end-diastolic pressure (LVEDP) and maximal dP/dt were recorded as in Group A. In Group C (n = 10) central haemodynamics were measured 10 min after i.v. metoprolol (0.5 mg.kg-1) and again 10-15 min after the addition of TEA. In Group D (n = 6) LVEDP and max dP/dt were measured as in Group C. The reduction in CO, SV, HR and max dP/dt was of the same magnitude with TEA and metoprolol. TEA lowered MAP by 17%, while metoprolol did not change MAP. Metoprolol caused an increase in LVEDP from 20.8 +/- 1.8 to 27.5 +/- 2.7 mmHg (2.8 +/- 0.2 to 3.7 +/- 0.4 kPa) (P less than 0.01), while TEA induced a decrease in LVEDP from 24.2 +/- 1.4 to 17.8 +/- 1.6 mmHg (3.2 +/- 0.2 to 2.4 +/- 0.2 kPa) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309538 TI - Analgesia for appendectomy: comparison of fentanyl and alfentanil in children. AB - During etomidate-N2O vecuronium anaesthesia for appendectomy, three groups of 13 children received fentanyl as a 10 micrograms.kg-1 loading dose and 2 micrograms.kg-1 increments in Group F, alfentanil as a 100 micrograms.kg-1 initial loading dose and either 20 micrograms.kg-1 increments in Group AB or 1 microgram.kg-1.min-1 continuous infusion in Group AI. On the basis of intraoperative heart rate changes, the opioid regimen was less efficient in Group AB (P less than 0.05). Based upon equianalgesic cumulative dosage, the alfentanil/fentanyl potency ratio was in the range of 1/10 to 1/13. The awakening time was similar in all groups, as were the duration of postoperative analgesia, the incidence of postoperative pain and the incidence of nausea and vomiting. We conclude that high-dose alfentanil is as efficient as fentanyl for intra and postoperative analgesia in children undergoing appendectomy. PMID- 2309539 TI - Thiopental binding to human serum albumin in the presence of halothane. AB - In vitro thiopental binding (substrate concentration 0.04.10(-3) M = 10 micrograms/ml) to 1% human serum albumin (HSA) increased significantly from 40.2% (= control) to 47.3% in the presence of 1.18.10(-3) M = 2.84 vol% halothane. A 4 fold higher halothane concentration (4.71.10(-3) M) had an even greater effect with an increase in the thiopental fraction bound to 55.5%. With a constant HSA concentration (1% or 5%) and thiopental concentrations in the range 0.01-1.5.10( 3) M or 0.01-0.38.10(-3) M, respectively, the halothane effect (increase in thiopental binding) was always evident, as well as in other experiments with constant thiopental concentration (0.04.10(-3) M) and variation in the HSA concentration (0.5-10%). Two classes of binding sites for thiopental were apparent at the HSA molecule. In the control experiments the following binding parameters were found: n1 = 0.01, k1 = 181.10(3) M-1; n2 = 45.73, k2 = 0.08.10(3) M-1, K = 5.47.10(3) M-1. In the presence of halothane the binding parameters changed as follows: n1 = 0.14, k1 = 29.4.10(3) M-1; n2 = 11.68, k2 = 0.42.10(3) M 1, K = 9.02.10(3) M-1. PMID- 2309540 TI - Circulatory monitoring of children during anaesthesia in low-field magnetic resonance imaging. AB - Anaesthesia for patients in a Magnetic Resonance Imaging (MRI) scanner provides some problems for the design of both the anaesthetic and the monitoring equipment. This report presents a technique for continuously displaying the heart rate during anaesthesia for children in an MRI scanner. The monitoring system used light to detect differences in skin capillary circulation, and the light was transferred to and from the patient via fiberoptic cables. After amplification, the signal was displayed "on line" on a cardioscope, thus continuously presenting heart rate and, in part, a qualitative view of the skin vascular resistance. PMID- 2309541 TI - The influence of midazolam on the plasma concentrations of bupivacaine and lidocaine after caudal injection of a mixture of the local anesthetics in children. AB - Twenty children undergoing surgery received a caudal block using 1 ml per kg of a mixture of 50% lidocaine (1%) and 50% bupivacaine (0.25%). They were randomly allocated to two groups, one of which received midazolam 0.4 mg/kg rectally as premedication. Midazolam administration resulted in a significantly lower AUC value for lidocaine but did not influence the plasma concentrations of bupivacaine. PMID- 2309542 TI - Muscle relaxants change myocardial metabolism in patients with ischemic heart disease during high-dose fentanyl anesthesia. AB - Although not unanimously accepted, high-dose fentanyl anesthesia has been associated with hemodynamic stability and little derangement of myocardial oxygen balance. This apparent inconsistency inspired us to investigate the effects on cardiac function and myocardial metabolism of stepwise increasing doses of fentanyl, accumulating to 15, 30, and 50 micrograms.kg-1, with the least possible interference from other drugs. Subjects were unpremedicated patients with ischemic cardiac disease scheduled for coronary artery bypass grafting or major vascular surgery. In an initial study employing succinylcholine for muscle relaxation, we found that heart rate (HR), coronary sinus blood flow (CSF) and coronary vascular resistance (CVR) remained unchanged, while systemic arterial pressure (SBP), rate-pressure product (RPP), coronary perfusion pressure (CPP) and left ventricular work (LVW) decreased. Myocardial uptake of oxygen (MVO2) and free fatty acids (FFA) both decreased in a dose-dependent manner. Arterial lactate concentration and myocardial lactate uptake both increased. These findings opposed the postinduction myocardial ischemia noted by some other investigators. In most of these studies pancuronium bromide had been used for muscle relaxation. Since the latter agent has been claimed to increase cardiac work, a second group of correspondingly diseased patients was studied in which succinylcholine was replaced by pancuronium bromide. In this group HR, RPP, CSF and MVO2 all increased at the lowest dose of fentanyl and HR additionally also at 30 micrograms.kg-1. The cardiac index was higher in the pancuronium group at the lowest and middle dose steps of fentanyl. Lactate uptake decreased with higher doses of fentanyl and relative myocardial lactate extraction declined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309543 TI - Metabolites of methohexitone do not contribute to its prolonged action on the central nervous system. AB - Methohexitone has been reported to have a prolonged action on the central nervous system (CNS) despite its relatively short elimination half-life. A hydroxy metabolite of methohexitone was identified, purified and isolated from the urine collected from eight surgical patients and five mongrel dogs anaesthetized with methohexitone. Using a rotarod device, the CNS-activity of the human and canine metabolites was tested in mice and compared to that of methohexitone. In this test, the metabolites showed CNS-depressant activity, but the ED50 (dose needed to affect 50% of the animals) of the metabolites was ten times higher than the ED50 of the parent drug. Because in patients, no traces of the hydroxy metabolite could be found in blood, and in dogs the plasma concentration of the metabolite was about two-thirds of that of the parent compound, it is unlikely that the residual CNS-effects of methohexitone are due to its major metabolite, hydroxymethohexitone. PMID- 2309544 TI - Effects of alfentanil on the responses to awake fiberoptic nasotracheal intubation. AB - Intubation conditions and pressor response were assessed in 30 healthy patients undergoing awake nasotracheal intubation. The patients were premedicated with peroral diazepam. All the patients were sedated with intravenous diazepam 0.1 mg/kg. Alfentanil 20 micrograms/kg or saline was administered in a double-blind fashion. Alfentanil caused moderate respiratory depression but significantly improved conditions for fiberoscopy. In the control group, arterial pressures and heart rate increased significantly immediately after tracheal intubation. These responses were attenuated by alfentanil. PMID- 2309545 TI - Sublingual buprenorphine as postoperative analgesic: a double-blind comparison with pethidine. AB - Buprenorphine and pethidine as postoperative analgesics were compared in 96 women having gynaecological operations by lower laparotomy. A fixed dose of the respective drug was given in a double-blind and double-dummy manner, initially intramuscularly and thereafter by sublingual buprenorphine (0.4 mg) or intramuscular pethidine (75 mg) at the request of the patient during the first 24 h postoperatively. Patients receiving buprenorphine had longer dose intervals and thus needed fewer doses. The analgesic effect, as assessed by a visual analog scale, was similar with both drugs. There were no significant differences between the groups regarding respiratory depression and nausea. It appears that sublingual buprenorphine is as effective and safe as intramuscular pethidine in the postoperative period. PMID- 2309546 TI - Dose-response to pancuronium in identical twins. AB - The dose-response to pancuronium was determined in identical twins within an hour with the same anesthetic technique. The dose-response curves did not differ from parallelism, but one infant was more sensitive to pancuronium than the other. The recovery rates were also different. The variation in the dose response to pancuronium seems to extend to identical twins. PMID- 2309547 TI - Epidural anesthesia for cesarean section in a patient with severe pulmonary hypertension. AB - The case of a parturient previously operated on for transposition of the great arteries is reported. On account of Eisenmenger's syndrome with high pulmonary vascular pressures, she was admitted to hospital with hemoptysis in the 27th week of gestation. At the end of the 34th week the child was delivered by elective cesarean section under epidural block. Bupivacaine 0.75% was administered as local anesthetic, and small incremental doses of local anesthetic proved capable of maintaining hemodynamic stability for the duration of the operative procedure. PMID- 2309548 TI - Does ephedrine influence newborn neurobehavioural responses and spectral EEG when used to prevent maternal hypotension during caesarean section? AB - The recovery of 16 infants born by elective caesarean section with spinal anaesthesia, in which either ephedrine or fluid load was used to prevent maternal hypotension, were studied using Scanlon's neurobehavioural tests and a computerized EEG. Neurobehavioural testing showed no differences between the ephedrine and the non-ephedrine groups of infants at ages of 3 h, 1 day, 2 days and 4-5 days, whereas the spectral EEG showed significant differences between the two groups during the first 2 h after delivery, which had disappeared 24 h later. It is suggested that small doses of ephedrine given to the mother i.v. to prevent hypotension during spinal anaesthesia have short-lived effects on the neonate's central nervous system, which will be detected in the spectral EEG, but not in neurobehavioural tests. PMID- 2309549 TI - Caloric nystagmus decay during parabolic flight. AB - In human subjects the caloric test was conducted during parabolic flight. The slow-phase velocity (SPV) of the caloric nystagmus increased proportionally to the value of the g-force. The nystagmus disappeared in microgravity, after an exponential SPV decay that showed a specific time constant (Tc). The average Tc value of this SPV decay is on a lower level than the one found after a sudden stop-test in the laboratory in a 1-g condition. Because of the exponential characteristics of the SPV decays and their Tc values, evoked in both conditions, a common working mechanism of cupular stimulation is likely. Most probably a fluid movement, caused either by a sudden stop in a 1-g condition or by weightlessness after a calorization, provokes a cupula flexion followed by a reflexion. The results support the Barany convection theory with regard to the endolymph movement following the caloric test. PMID- 2309550 TI - The effect of external stimuli on cultured rat middle ear epithelium. I. Extracellular calcium concentration. AB - The effect of the extracellular calcium concentration on serially cultured rat middle ear epithelium was investigated with phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy, as well as by a method to induce cornified envelope formation with a calcium ionophore. The results show that calcium concentration affects cell morphology and terminal differentiation. Furthermore, a role in the proliferation rate, secretory activity and migration seems likely. Since the extracellular calcium concentration may fluctuate locally during osteoresorption or osteodeposition, both of which occur during otitis media, this concentration might be an important factor in the pathogenesis of both acute and chronic otitis media. PMID- 2309551 TI - Inflammatory cells in chronic middle ear disease. Value of lymphocyte subset determination in ear surgery. AB - Lymphoid cell subsets were studied in biopsy specimens of uninfected and infected ear canal epidermis, tympanic membrane, cholesteatoma epithelium, and middle ear and antrum granulation tissue. All specimens showing uninfected squamous epithelium, including those of cholesteatoma membrane, contained only a few lymphoid cells. Biopsies of infected squamous epithelium showed enhanced Ts/c activity in the subepithelial layer. Granulation tissue showed normal Th/i activity. B-cells and NK cells appeared in small numbers. Lymphoid cell subset analysis is indicated in ears reconstructed with allograft material to detect signs of rejection. It is of little value in cases of chronic inflammatory middle ear disease which have not previously been operated upon. PMID- 2309553 TI - The influence of leukotrienes and platelet activating factor on mucociliary activity in the rabbit maxillary sinus. AB - Inflammatory mediators released in the airways during allergic reactions can affect the mucociliary system. Leukotrienes and platelet activating factor have been shown to affect the mucociliary activity in various cell preparations. The in vivo effects of these inflammatory mediators on mucociliary activity in rabbit maxillary sinus were investigated using a photoelectric technique. Leukotrienes C4 and D4 in the dose range 0.01-10.0 nmol/kg did not alter mucociliary activity significantly, either when given as bolus injections or as intraarterial infusions. Platelet activating factor had no effect in the dose range 0.001-0.1 nmol/kg. A dose of 1.0 nmol/kg increased mucociliary activity by 20.2 +/- 5.5% but produced adverse respiratory and circulatory effects at the same time. It is concluded that the inflammatory mediators leukotrienes C4, D4 and platelet activating factor have no essential regulatory influence on mucociliary activity in the upper airways of the rabbit. PMID- 2309552 TI - A comparative study of enzyme histochemical features in the gerbilline and human cholesteatoma. AB - Spontaneous and experimentally induced cholesteatoma in the Mongolian gerbil has been found to exhibit histopathological similarities to human aural cholesteatoma and has been suggested as an experimental model for studies of the clinical situation. In an attempt to further characterize this model, we compared experimentally induced cholesteatomas in the external auditory canal from gerbils with those of the human ear by means of a correlated histopathologic and enzyme histochemical study. The human and gerbilline cholesteatomas revealed similar histopathologic features. Even enzyme histochemically, the human and experimentally induced cholesteatomas demonstrated similar features. Thus glucose 6-phosphate dehydrogenase activity, an indicator of oxidative metabolism, was demonstrated especially in the stratum granulosum cells of the heavily orthokeratinizing squamous epithelium adjacent to the cholesteatomas. The human ear canal skin also revealed enzyme histochemical characteristics similar to the squamous epithelium lining the human cholesteatoma. The hydrolytic enzyme activity (leucyl-aminopeptidase) was strong in the connective tissue surrounding human cholesteatoma when compared with that of ear canal skin. In the gerbilline cholesteatoma, this activity was demonstrated especially in the connective tissue adjacent to eroded bone, which possibly may facilitate cholesteatoma progression. We conclude that experimentally induced cholesteatoma has both histophatological and enzyme histochemical similarities to human aural cholesteatoma and therefore it is suggested that the gerbilline model may be used for studies on the development of human cholesteatoma. Our results support the view that cholesteatoma may originate from migrated hyperkeratinizing cells from the epidermis of the tympanic membrane or the meatus. PMID- 2309554 TI - The plasticity of compensatory eye movements in rotatory tests. I. The effect of alertness and eye closure. AB - Fifteen voluntary subjects with a mean age of 26 years (17-39), participated in two rotatory experiments. The rotatory test used was sinusoidal harmonic acceleration (SHA) test at frequencies of 0.01-0.32 Hz. Compensatory eye movements were measured by means of EOG. Experiment A included rotation in darkness during alerting tasks (day 1), rotation in darkness with no tasks (day 2) and rotation in darkness during alerting tasks (day 3). In the alertness tests, the gain varied between 0.5 and 0.77. Phase values decreased with increasing frequency. The alertness results between days 1 and 3 did not differ in gain or phase. The gain of day 2 (no tasks) displayed significantly reduced gain at all frequencies, and a more pronounced decrease in phase than in the alertness tests. Experiment B comprised testing with eyes open (day 1) and eyes closed (day 2) during alerting tasks. These tests displayed significantly decreased gain at all frequencies with eyes closed compared with eyes open and with more negative phase at 0.08-0.32 Hz with eyes closed. The results indicate a central effect of the alertness level on compensatory eye movements, and the effect of eye closure might be explained by bio-mechanical and possibly even central effects on the eye movements. In low-frequency testing, as short a test time as possible should be used, and due to different alertness levels, the results should be evaluated with great caution. PMID- 2309556 TI - Short vestibulo-ocular reflex time constants associated with oculomotor pathology in multiple sclerosis. AB - Significantly short vestibulo-ocular reflex (VOR) time constants were found in significant high numbers in patients with multiple sclerosis who had oculomotor dysfunction, especially when this dysfunction comprised both the smooth pursuit/optokinetic and the saccadic systems. Some time constants were in the range of 2.5-6 s, i.e. shorter than the presumed time constant of the primary afferent canal neuron. Increase in oculomotor impairment was accompanied by a decrease in time constants in some patients, whereas others showed a combined renormalization of previously disturbed oculomotor function and short time constants. Significantly high numbers of combinations of asymmetry in oculomotor dysfunction and a directional preponderance in time constant were observed, with the shorter time constant on the side of the (more severe) defect. PMID- 2309555 TI - Image cytometry DNA analysis of diethylnitrosamine-induced dysplasias and invasive squamous cell carcinomas of the esophagus in mice. AB - The nuclear DNA content was assessed by image cytometry in squamous epithelial dysplasias and invasive squamous cell carcinomas of the esophagus induced by diethylnitrosamine (DEN) in mice. The study comprises 48 lesions: 27 lesions with low grade (i.e. slight and moderate) dysplasia, 18 with high grade dysplasia (i.e. severe dysplasia and CIS), and 3 with invasive squamous cell carcinoma. In addition, 5 parallel run control specimens were also investigated. The results demonstrated that only 3.7% (or 1/27) low grade dysplasias but as much as 72.2% (or 13/18) high grade dysplasias, and all three invasive squamous cell carcinomas displayed non-diploid DNA values. Three of 18 high grade dysplasias and all three invasive squamous cell carcinomas demonstrated aneuploid cell nuclei. The results of the present work indicate that the esophageal mucosa of the mouse permit investigation--under controlled conditions--of the nuclear DNA alterations occurring during carcinogenesis in this organ. The results presented herein thus substantiate the theory of increasing DNA aberrations occurring during carcinogenesis in the human esophagus. PMID- 2309557 TI - Sequence of exposure to noise and toluene can determine loss of auditory sensitivity in the rat. AB - Rats were exposed to noise (100 dB Leq, 10 h/d, 7 d/w, 4 w), or to toluene (1,000 ppm, 16 h/d, 7 d/w, 2 w), or to noise followed by toluene. Auditory sensitivity was tested before exposure, and 1 to 4 weeks after exposure, by brainstem audiometry using a 1/3-octave filtered sine wave stimulus at the frequencies 1.6, 3.15, 6.3, 12.5 and 20.0 kHz. Some auditory impairment was observed after all exposures. The sensitivity loss after exposure to noise followed by toluene was greater than that recorded after exposure to noise alone or toluene alone, but did not exceed the summated loss caused by noise alone and toluene alone at any frequency. This result contrasts with the earlier reported effect of the same exposures in the reversed order. It is concluded that the exposure sequence can determine the extent of auditory impairment. PMID- 2309558 TI - Right-left correlation in guinea pig ears after noise exposure. AB - In order to investigate whether experimental material consisting of noise-exposed animals should be regarded as 'ears' or 'animals', a comparison was made between the permanent threshold shifts in the right and left ears in 53 groups of noise exposed guinea-pigs, with 5 animals in each group. The action potential (N1) thresholds were measured at fourteen frequencies in both ears. In the noise exposed animals, the threshold elevations were up to 40 dB. The average right left correlation coefficient within each group was about 0.79, regardless of noise energy. The degree of correlation was significantly greater after impact noise than after continuous noise. As a consequence of the high right-left correlation, the informative value of measuring a second ear in the same animal was, in our experiments, only 11% of that of the first one. No correlation could be found between the degree of skin pigmentation and the threshold elevation. PMID- 2309559 TI - Effect of furosemide upon morphology of hair bundles in guinea pig cochlear hair cells. AB - Furosemide was administered by intraperitoneal injection and intracochlear perfusion. The peak-to-peak amplitude of the cochlear microphonic at high sound intensities was reduced however the drug was administered. After a period of time ranging from 1-4 h following drug application, cochleae were fixed and prepared for scanning electron microscopy to examine the hair cells. Changes in the hair bundles from basal turns tended to be more extensive than those of more apical turns. Initially there was an increase in the granularity of the surface of the stereociliary membrane and a tendency for cross-links to swell, stretch and break. Later, the surface texture of stereocilia became smoother than normal, and hair cells in the basal turns showed extensive erosion and fracture of cross links. Tip links could survive even when extensively stretched. It is possible that the morphological changes in stereocilia reported here do not arise from direct actions of furosemide, but indirectly, from perturbations of the ionic composition of cochlear fluids induced by effects of the drug upon the stria vascularis. PMID- 2309560 TI - Intermediate filament proteins in the embryonic inner ear of mice under normal conditions and after exposure to ototoxic drugs. AB - The expression of the intermediate filament subclasses cytokeratins (CKs), vimentin, and neurofilament triplet proteins (NFs) was analysed in the embryonic inner ear of the CBA/CBA mouse, in vivo and in vitro, using well-defined monoclonal antibodies. Some of the cultured inner ears were exposed to 1-10 micrograms/ml of the ototoxic drugs gentamicin, ethacrynic acid or cisplatin. There was no difference in the expression of IF pattern in the cultured inner ears as compared with the in vivo developed labyrinths. Exposure to the ototoxic drugs did not affect the expression of CKs, vimentin, or NFs. CKs 8 and 18 were identified in all inner ear epithelia. In the mature hair cells, only the apical surfaces showed immunoreactivity to CKs. In addition, CKs 7 and 19 were visualized in the epithelia involved in maintaining endolymph homeostasis. The ganglion cells showed co-expression of CKs, vimentin and NFs, each having a characteristic localization in the cells. PMID- 2309561 TI - Rotated stereociliary bundles and their relationship with the tectorial membrane in the guinea pig cochlea. AB - Hair cells with rotated stereociliary bundles have been observed in the cochleae of control and kanamycin-treated guinea pigs. The affected outer hair cell bundles have a variable degree of rotation, with some being completely reversed. The inner hair cells are more rarely affected, and only small areas of an individual inner hair cell bundle are abnormal. In counts from ten cochleae, the number of outer hair cells with rotated bundles was most commonly between 10% and 20%, with almost 27% of all outer hair cells affected in the most extreme case. The rotated outer hair cell bundles often have distorted outlines but in other respects closely resemble normal bundles. In particular, they have the usual gradation in stereociliary height, intracellular cross-links and intercellular links to adjacent normally-orientated bundles. There are also corresponding imprints in the tectorial membrane which match the pattern of the stereocilia. In kanamycin-treated guinea pigs, imprints of both normal and rotated hair bundles are present, even when the corresponding bundle is absent, and there are frequently remnants of stereocilia inserted in the imprints. These observations suggest that, apart from their abnormal orientation, the rotated bundles are similar to normal bundles in both their organization and association with the tectorial membrane. The implications of this with respect to transduction and cochlear mechanics are discussed. PMID- 2309562 TI - The role of macrophages in the disposal of degeneration products within the organ of corti after acoustic overstimulation. AB - We analysed the ultrastructure of scavenger cells in the organ of Corti of 10 guinea pigs at five different intervals (5 min, 4 h, 24 h, 5 days and 28 days) after acoustic overstimulation. There was evidence of phagocytic cells only at 5 days after noise exposure. Dendritic macrophages were seen phagocytosing degenerating cells and debris in the tunnel of Corti and in the region of the outer hair cells. Transforming monocytes in this area and leukocytic accumulation within the spiral lamina vessel suggest that these cells may be derived from blood-borne monocytes. These cells may contribute to local disposal of intracochlear cell degeneration products and thus to healing of organ of hearing after induction of noise-induced damage. PMID- 2309563 TI - The clinical significance of head-shaking nystagmus in the dizzy patient. AB - The clinical significance of horizontal head-shaking nystagmus (HSN) was evaluated in 85 patients who complained of dizziness and vertigo. This was done by comparison of the horizontal head-shaking test with routine rotatory and caloric vestibular testing. We found that HSN evoked by horizontal head-shaking is a highly sensitive way to detect unilateral vestibular hypofunction. Except in patients with additional central vestibular imbalance or in patients with Meniere's disease, the direction of horizontal HSN is highly significant in indicating the side of the lesion, with the fast phase beating toward the intact side. However, horizontal HSN is not specific in distinguishing peripheral hypofunction from more central vestibular imbalances. Peripheral vestibular hypofunction as well as a central asymmetry of the vestibular velocity storage mechanism can each separately or in combination produce horizontal HSN. Thus, while the head-shaking manoeuvre is an excellent bedside-test to detect unilateral vestibular hypofunction, further rotatory and caloric testing is still necessary to clarify the patient's condition. PMID- 2309564 TI - Pressure relationship between perilymph and endolymph in guinea pigs. AB - The pressure difference between the perilymph and the endolymph was studied in guinea pigs, using two sets of a servo-nulling system. Asphyxia caused characteristic pressure changes both in the perilymph and in the endolymph, but no pressure difference was seen between them. When the perilymphatic space was opened to the atmosphere, asphyxia did not cause such dynamic pressure changes either on the perilymph or the endolymph. An increase in the perilymphatic pressure induced by the infusion of artificial cerebrospinal fluid into the subarachnoid space resulted in an increase in the endolymphatic pressure, but no pressure difference between the endolymph and the perilymph was evident, regardless of the patency of the vestibular aqueduct. The authors conclude that the endolymphatic pressure is dependent on the perilymphatic pressure and there is no pressure difference between them. PMID- 2309565 TI - Mechanism of erythrocyte trapping in ischaemic acute renal failure. AB - Forty-five minutes of warm ischaemia and 20 min of recirculation in the rat kidney was found to result in (1) a massive transient extravasation of plasma upon recirculation and (2) an increase in plasma-lymph transport of proteins during the first hours after onset of circulation. This was accompanied by trapping of erythrocytes, as determined with 51Cr-labelled erythrocytes, in the capillaries, mainly in the inner stripe of the outer medulla. At scanning electron microscopy of vibratome sections, the trapping appeared as aggregates of polygonally shaped erythrocytes. It is concluded that 45 min of ischaemia and 20 min of recirculation results in an increase in the permeability of the renal capillaries. This increase leads to extravasation of capillary plasma with consequent local haemoconcentration, causing an increase in vascular resistance and in capillary hydrostatic pressure. This elevated pressure will, in turn, lead to perpetuating extravasation of plasma, further haemoconcentration and so on, eventually resulting in dense packing of polygonal erythrocytes, obstructing the blood flow. It is believed that oxygen-derived free radicals generated in the early recirculation phase contribute to the increase in macromolecular permeability, since the scavenger bovine superoxide dismutase and allopurinol, a xanthine oxidase inhibitor, were found to prevent this unfavourable chain of events. PMID- 2309566 TI - The long-term outcome of post-ischaemic acute renal failure in the rat. I. A functional study after treatment with SOD and sucrose. AB - The long-term outcome in rat kidneys subjected to 45 min of warm ischaemia with no treatment and after administration of 20 mg superoxide dismutase (SOD) and of SOD combined with 2 ml of a 12% sucrose solution was studied by the micropuncture technique. It was found that, although in the acute phase SOD prevented trapping of erythrocytes in the medullary vasculature and that SOD + sucrose also prevented the formation of tubular obstruction, the long-term results as studied 1 week and 1 month after the primary ischaemic insult were virtually identical. This was due to the formation of new obstructions, during the first week, mainly in the thick ascending limb of Henle's loop. After 1 month the proximal tubular free-flow pressure and the single-nephron filtration rate had returned to normal. However, since the total glomerular filtration was only one-third of that under normal conditions, it would seem that two-thirds of the nephrons had undergone complete degeneration. This degeneration was probably the result of persistent tubular obstruction. The tubular degeneration was also accompanied by a reduction in urine osmolality and potassium secretion. PMID- 2309567 TI - The long-term outcome of post-ischaemic acute renal failure in the rat. II. A histopathological study of the untreated kidney. AB - Histopathological changes in kidneys subjected to 45 min of isothermic unilateral ischaemia in the acute phase and 1 week and 1 month after primary damage were studied at the electron microscopic level. During the first week after recirculation long homogeneous cylinders, probably consisting of Tamm-Horsfall protein, developed in the medullary parts of the nephron, and after 1 month of recirculation there were two types of nephrons: (1) nephrons with a normal histological appearance and (2) degenerated nephrons. The latter group gave rise to crypts in the outer cortical area. It is hypothesized that the generation of the long Tamm-Horsfall cylinders in the thick ascending limb of the loop of Henle plays an important role in the long-term outcome of the kidney after the primary damage. The persistent blockade caused by these cylinders will lead to precipitation of the ultrafiltrate, resulting in long cell-protein cylinders in the proximal parts of the nephron. This precipitation will proceed in the retrograde direction, reaching the mother glomeruli, eventually leading to total degeneration of the nephron. PMID- 2309569 TI - Effect of papillary exposure on intrarenal distribution of glomerular filtration rate and of plasma flow. AB - Removal of the renal pelvis in order to expose the renal papilla has been shown to cause impairment of the renal concentrating ability by an unknown mechanism. To study this phenomenon, urine osmolality (Uosm), single-nephron glomerular filtration rate (SNGFR) in outer and inner cortical nephrons and the inner and outer medullary plasma flow were determined. Measurements were performed on groups of rats before (control) and 15, 45 and 90 min after exposure of the left renal papilla. Rats with an intact ureter were studied in parallel to see whether the variables varied within the 90-min period of the study. In all groups of animals with an exposed papilla, Uosm was lower than in non-exposed animals. Outer cortical SNGFR in rats with exposed papillae, regardless of time, was not different from that in control rats. Inner cortical SNGFR after 45 and 90 min of exposure did not differ from that in controls, but after 15 min of exposure it was lower than in control animals. Outer and inner medullary plasma flow did not differ between rats with exposed papillae and controls, irrespective of exposure time. In conclusion, papillary exposure results in a permanent decrease in urine osmolality. This impairment of the concentrating ability cannot be attributed to prolonged changes in renal haemodynamics. PMID- 2309568 TI - Capsaicin and histamine antagonist-sensitive mechanisms in the immediate allergic reaction of pig airways. AB - The airway vascular and bronchial responses were studied in pigs sensitized with Ascaris suum. Ascaris, histamine (H) and capsaicin aerosol all induced a clear cut increase in blood flow in the nasal, laryngeal and bronchial circulation with a decrease in vascular resistance of 20-40%. When delivered to the lung both ascaris and histamine, but not capsaicin, caused pulmonary airflow obstruction with increase in resistance and a fall in dynamic compliance of 40-70%. After pretreatment of pigs with a combination of the H1- and H2-receptor antagonists terfenadine and cimetidine, the vascular and bronchial responses were strongly reduced to both histamine (by greater than 77%) and ascaris (by greater than 58%), but not to capsaicin aerosol. The bronchoconstriction to histamine was found to be mediated by H1-receptors only, while both H1- and H2-antagonists were necessary to block the vasodilatory response, with H2-receptors being more important in the bronchial circulation and H1-receptors being more important in the laryngeal and nasal circulation. Furthermore, when pigs were pretreated with capsaicin systemically 2 days before the experiment, the vasodilation was decreased upon capsaicin (by 80%), ascaris (by greater than 40%) and histamine (by greater than 50%) aerosol challenge. When histamine was administered intravenously the desensitizing effect of capsaicin pretreatment was much less pronounced. The effect of capsaicin desensitization on the pulmonary obstruction upon ascaris and histamine challenge was limited to a 60% reduction of the fall in dynamic compliance and a delayed peak in resistance upon ascaris challenge. We conclude that histamine is one of the main vasodilatory mediators released upon allergen challenge at three different levels of the pig airways. A considerable part of the histamine effect is indirect and probably due to activation of capsaicin-sensitive sensory nerves. PMID- 2309570 TI - Influence of mild sodium depletion upon peripheral and centrally mediated effects of intravenous angiotensin II in the goat. AB - Previous evidence for cerebral sodium/angiotensin interaction concerning centrally mediated effects of angiotensin II (AII) provided the incitement to compare in goats effects of i.v. AII during sodium repletion (SR) with those obtained during mild sodium depletion (SD). The experiments were performed in the euhydrated as well as hyperhydrated animals, and AII was infused for 10 min at 40 pmol kg-1 min-1. It was confirmed that SD is associated with elevated plasma aldosterone concentration (PA) and (as regards aldosterone secretion) a sensitization of the adrenal cortex. In contrast to PA, the plasma cortisol (PC) response to i.v. AII was significantly reduced during SD, apparently due to diminished cerebral sensitivity to circulating AII. A similar SD-associated attenuation was observed during euhydration as regards release of arginine vasopressin (AVP) in response to i.v. AII, and during hyperhydration as regards the antidiuretic effect of the octapeptide. It was confirmed that the pressor effect of i.v. AII becomes markedly reduced during SD. However, in spite of this, the associated bradycardia remained the same during SR and SD, suggesting that SD also attenuated the centrally mediated chronotropic effect of AII. PMID- 2309571 TI - Studies of cholera toxin-induced changes of alkaline secretion and transepithelial potential difference in the rat intestine in vivo. AB - A pH-stat technique was used to investigate the effects of cholera toxin (CT) on alkaline secretion from denervated intestines (jejunum, ileum, colon) in anaesthetized rats. Transepithelial potential difference (PD) was also followed in some experiments. CT, given intraluminally, caused a marked increase in jejunal alkaline secretion, whereas only a small effect was observed in the ileum and no apparent effect was noted in the proximal colon. The pronounced increase in jejunal alkaline secretion was found to be inhibited by 10-25% by hexamethonium (10 mg kg-1 body wt i.v.) and similarly by serosal application of lidocaine, whereas atropine (0.25 mg kg-1 body wt i.v.) had no effect. Thus the cholera toxin-induced alkaline secretion in the jejunum is attributed mainly to a non-nervous mechanism. The small effect of CT on ileal alkaline secretion observed in this study contrasts with the high ileal bicarbonate concentration reported in cholera by authors who estimated the concentration from the total carbon dioxide/bicarbonate contents. This discrepancy may be explained by a CT evoked increased transport of the coupled Na+/H+ and Cl-/HCO3- exchangers, which cannot be measured with the pH-stat technique used in this study. PMID- 2309572 TI - Water intake and changes in plasma and CSF composition in response to acute administration of hypertonic NaCl and water deprivation in sheep. AB - Water intake and changes in plasma and cerebrospinal fluid (CSF) composition were measured in response to intracerebroventricular (i.c.v.) and intracarotid infusions of hypertonic NaCl solutions and after 48 h of water deprivation in sheep. Significant interindividual differences in dipsogenic sensitivity to i.c.v. NaCl were found, whereas no such differences were observed in response to intracarotid infusion of hypertonic NaCl. In the more sensitive animals, the increase in CSF [Na] at initiation of drinking during i.c.v. infusion did not differ significantly from the increase in plasma [Na] seen at the thirst threshold during intracarotid infusion of 1 M NaCl. The thirst-eliciting infusions of hypertonic NaCl into the carotid arteries were associated with a small, significant, increase in CSF [Na], which however did not differ from that caused by an i.c.v. non-dipsogenic 'control' infusion of a slightly hypertonic (0.154 M) NaCl solution. Water deprivation for 48 h induced increases in CSF and plasma [Na] similar to those observed at the onset of drinking in response to i.c.v. and intracarotid infusions of hypertonic NaCl. However, the dehydrated animals drank about four times the amount of water consumed in response to the separate treatments with hypertonic NaCl. It is concluded that significant interindividual differences in dipsogenic sensitivity to osmotic stimuli are present in sheep, and that these differences may not necessarily be simultaneously expressed on both sides of the blood-brain barrier. The thirst eliciting effect of intravascular infusion of hypertonic NaCl may be induced without concomitant increase in CSF [Na] and/or osmolality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309573 TI - A study of the effect of narcosis on oviductal activity using a method for continuous monitoring of this activity. PMID- 2309574 TI - Further evidence for a prejunctional action of neuropeptide Y on cholinergic motor neurons in the rat uterine cervix. PMID- 2309575 TI - Alteration of vitamin D metabolism in Mexican-Americans. AB - Studies were performed to investigate vitamin D metabolism in Mexican-Americans. Groups of 15 whites and 16 Mexican-Americans ranging in age from 18 to 41 years were evaluated. All of them were within 25% of their ideal body weight. Each of them was admitted to the Clinical Research Center of the University of Texas Health Science Center and placed on a daily diet estimated to contain 400 mg calcium and 900 mg phosphate. It was found that whereas serum vitamin D (1.8 +/- 0.5 versus 7.6 +/- 1.3 ng/ml, P less than 0.001) and serum 25-hydroxyvitamin D (9 +/- 1 versus 17 +/- 2 ng/ml, P less than 0.01) were significantly lower and serum 1,25-dihydroxyvitamin D (37 +/- 2 versus 28 +/- 2 pg/ml, P less than 0.001) was significantly higher in the Mexican-Americans than in the whites, serum calcium (9.1 +/- 0.1 versus 9.2 +/- 0.1 mg/dl), magnesium (1.84 +/- 0.07 versus 1.80 +/- 0.07 mEq/liter), and Gla protein (19 +/- 3 versus 21 +/- 2 ng/ml) were not different in the two groups. Urinary calcium (144 +/- 14 versus 124 +/- 16 mg/day), phosphate (672 +/- 51 versus 683 +/- 44 mg/day), sodium (110 +/- 8 versus 99 +/- 9 mEq/day), potassium (43 +/- 4 versus 49 +/- 3 mEq/day), and magnesium (7.3 +/- 0.7 versus 7.7 +/- 0.5 mEq/day) and creatinine clearance (173 +/- 14 versus 154 +/- 7 liters/day) were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309576 TI - Validation of the bone Gla protein (osteocalcin) assay. PMID- 2309577 TI - Concentration of bone elements in osteoporosis. AB - In aging and in osteoporosis, decreased bone density is associated with decreased bone mass. However, changes in the bone mineral phase remain a matter for investigation. In particular, it is unknown whether bone mineral loss is directly related to reduction in bone mass or associated with changes in the concentration of mineral elements in mineralized bone tissue. In this study, the cortical bone concentration of elements was determined in biopsies of the ilium from 33 subjects (12 controls and 21 individuals with untreated severe osteoporosis). Calcium and phosphorus concentrations were evaluated in cortical and trabecular bone using energy-dispersive x-ray (EDX) microanalysis and inductively coupled plasma optical emission spectrometry (ICPOES). Bone concentrations of Na, K, Mg, Cu, Zn, Fe, Sr, Al, B, and Si were also determined in cortical bone using ICPOES. Additionally, the concentration of F in cortical bone was measured with a specific ion electrode and the concentration of Pb was determined by atomic absorption spectrometry. In mineralized bone tissue there was no significant age dependent variation in the concentration of Ca, P, or other elements either in controls or in osteoporotic subjects. Moreover, the concentration of elements in bone tissue did not differ in the two groups. These results suggest that the decrease in bone density in osteoporosis is directly related to evolution of the bone mass, without detectable changes in the concentration of elements in bone. PMID- 2309578 TI - Characterization of the latent transforming growth factor beta complex in bone. AB - Transforming growth factor beta (TGF-beta) is a 25 kD multifunctional polypeptide with pronounced effects on the proliferation and differentiation of a variety of cells in vitro. TGF-beta is a potent regulator of the activity of cells with the osteoblast phenotype and of isolated osteoclasts. It is released in increased amounts by bone cultures stimulated to resorb. Organ cultures of neonatal mouse calvaria produce TGF-beta as an inert large-molecular-weight complex that must be dissociated to release biologically active TGF-beta (5-8 ng/ml). We have shown recently that stimulated isolated avian osteoclasts release active TGF-beta from this bone-derived biologically latent form. In this report we have characterized this bone latent form of TGF-beta. Only small amounts of active TGF-beta (less than 0.5 ng/ml) and no free binding protein are detectable in conditioned medium from bone cultures. Active TGF-beta can be detected in acid-treated calvarial conditioned media in which none or only minute amounts could previously be detected. Following incubation at 37 degrees C, this activated TGF-beta gradually loses activity. Cross-linking studies using 125I-labeled TGF-beta show that this loss of activity is due to TGF-beta binding to a protein of approximately 300 kD. The TGF-beta latent complex accumulates in a linear manner and is stable in the presence of serum and the protease trypsin. Increases in temperature and pH extremes dissociate the complex to release active TGF-beta. Decreases in pH result in an exponential increase in TGF-beta activity. Significant activation of the latent TGF-beta was detectable at pH values as high as 4 and 5. Since the osteoclastic microenvironment is acidic during bone resorption, these data suggest that this acidic microenvironment may regulate TGF-beta activity by releasing active TGF-beta from its latent complex. PMID- 2309579 TI - Bone Gla protein (osteocalcin) assay standardization report. AB - The major conclusion of this study is that the different laboratory assays for serum BGP give a reasonably consistent picture of bone metabolism in the metabolic bone diseases examined only if the results are expressed as a percentage of serum BGP levels in normal individuals. This requires that all laboratories establish a mean control serum BGP value in an appropriate population of normal individuals. Since BGP levels determined by different laboratories on the same serum sample can vary by more than fourfold, the absolute serum BGP levels determined in one laboratory cannot be compared directly with the serum BGP levels determined in another. Although we cannot comment on the efficacy of different laboratory assays for serum BGP as measures of bone metabolism in disease states that were not examined, such as osteoporosis, it is clear that the large differences between laboratory assays make it imperative that all interlaboratory comparisons be based on values expressed as a percentage of serum BGP in an appropriate population of normal individuals. PMID- 2309580 TI - Aluminum administration in the rat separately affects the osteoblast and bone mineralization. AB - Aluminum administration in the experimental animal results in osteomalacia as characterized by osteoid accumulation and decreased mineralization. Previous in vivo and in vitro studies have indicated that either aluminum directly inhibits mineralization or is toxic to the osteoblast. In the present study, PTH was continuously infused in rats with aluminum-induced osteomalacia to evaluate whether aluminum administration decreased mineralization without a concomitant decrease in osteoblasts. Four groups of rats were studied: chronic renal failure (CRF); CRF + aluminum (AL); CRF + PTH; and CRF + PTH + AL. Rats were sacrificed 5 and 12 days after aluminum or diluent administration; in the PTH groups, bovine PTH (1-34) was administered at 2 units/h via a subcutaneously implanted Alzet pump. Aluminum administration decreased osteoblast surface, increased osteoid accumulation, and produced a cessation of bone formation. The infusion of PTH alone increased osteoblast surface and bone formation. The simultaneous administration of aluminum and PTH resulted in an osteoblast surface intermediate between aluminum and PTH alone; however, despite a PTH-induced restoration of osteoblast surface, bone formation did not increase. These findings indicate (1) aluminum is toxic to osteoblasts and also directly inhibits mineralization even when osteoblasts are not decreased; (2) PTH is capable of increasing osteoblasts even in the presence of aluminum; and (3) despite a PTH-induced increase in osteoblast surface, mineralization of osteoid was not improved. PMID- 2309581 TI - Parathyroid hormone is not required for normal milk composition or secretion or lactation-associated bone loss in normocalcemic rats. AB - To determine if parathyroid hormone (PTH) is essential for lactation in rats, the parathyroid glands were removed surgically during the first week of lactation and the rats were given a diet containing a high calcium-phosphorus ratio to maintain a normal serum calcium concentration. Lactating rats were placed on diet containing 1.2% calcium (Ca) and 0.8, 0.6, or 0.4% phosphorus (P) on day 2 postpartum (PP) and were parathyroidectomized (PTX) at 4-6 days PP. At 10 days PP serum Ca was 10.5 +/- 0.2 mg/dl (mean +/- SEM) for PTX rats and 10.4 +/- 0.3 mg/dl in sham-operated lactating rats when the diet contained 0.6% P. When the diet P was 0.8%, the litters gained little or no weight and serum Ca fell to 6.9 +/- 0.6 mg/dl by day 10 PP in PTX rats compared with 10.2 +/- 0.2 mg/dl in sham rats. PTX rats fed the diet containing 1.2% Ca and 0.6% P maintained a normal serum Ca level until at least day 18 PP, but their serum P levels fell gradually from approximately 5 mg/dl at 10 days to 3 mg/dl at 18 days PP. In spite of this hypophosphatemia, the litters of PTX and sham rats had gained the same amount of weight by age 16 days, indicating equal milk production in the two groups. Milk Ca, P, and total solids were not significantly different between PTX and sham rats on day 11 PP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309582 TI - Production of both interleukin-1 alpha and beta by newborn mouse calvarial cultures. AB - The conditioned medium (CM) from 4-6 day newborn mouse calvarial cultures was found to contain thymocyte comitogen proliferation activity. This activity was blocked by an antiserum to murine interleukin-1 alpha (IL-1 alpha) but not by an antiserum to murine interleukin-1 beta. The release of thymocyte comitogen proliferation activity from the cultures did not appear dependent on endotoxin and was not associated with detectable interleukin-2 activity in the CM. Activity in the CM eluted from a gel filtration column with a peak Mr of 16-18 kD (the Mr of mature murine IL-1 alpha and beta is 17 kD). Western immunoblots of 100-fold concentrated CM demonstrated only a single 33 kD band with an antiserum to murine IL-1 beta and no bands with an antiserum to murine IL-1 alpha. However, this assay was relatively insensitive (limit of detection 1-10 ng compared with 1-10 pg for the thymocyte comitogen proliferation assay). Immunoprecipitation of [35S]methionine-labeled CM with three different anti-IL-1 alpha antisera, a more sensitive assay, demonstrated 15-17 kD bands in all cases. These results demonstrate that 4-6 day newborn mouse calvarial cultures spontaneously release 17 kD IL-1 alpha and 33 kD IL-1 beta into their conditioned medium. It appears that although 17 kD IL-1 alpha is the major bioactive form in the CM, 33 kD IL-1 beta is present in greater amounts. These results also suggest that local production of IL-1 can regulate bone cell function and may play a role in bone growth and remodeling. PMID- 2309583 TI - Long-term organ culture of embryonic chick femora: a system for investigating bone and cartilage formation at an intermediate level of organization. AB - Bone organ culture is an experimental system in which skeletal cells remain within their extracellular matrix but are removed from systemic influences. Femurs from 14-day-old chick embryos, which contain bone and cartilage matrix in approximately equal proportions, were cultured for up to 9 days in a serum-free medium. Cell proliferation, differentiation into chondrocytes and osteoblasts, formation of bone and cartilage matrix, and in vitro mineralization as well as bone and cartilage resorption were assessed using histologic and analytic methods. Particular attention was paid to the differences between cartilage and bone growth and to interpreting analytic data in the light of histologic observations. The first 2 days of culture represented an "adaptation" period, characterized by the release of intracellular enzymes into the culture medium, probably as a consequence of cell breakdown. Days 3-9 in culture represented a period of "steady growth" during which skeletal cells continued to multiply in the absence of fetal serum and to secrete large amounts of bone and cartilage matrix. De novo mineralization could be induced by Ca-beta-glycerophosphate, but calcium deposits in tissues other than bone and cartilage were also induced. Resorption of bone or cartilage matrix was virtually absent. Bone organ culture facilitates the study of bone and cartilage formation at an intermediate level of organization and thereby provides the necessary link between in vivo studies and investigations at the cellular level. PMID- 2309584 TI - [Consideration on transfusion in urologic surgery--a retrospective study on homologous and autologous transfusions]. AB - To obtain data for promoting autologous transfusion in urologic surgery, the cases of perioperative homologous transfusions in the past 5 years are reviewed. Although the mean perioperative homologous blood transfusion rate was not so high (10.2%), the rate in common urological surgery was comparatively high (eg. radical nephrectomy 39.4%, simple or palliative nephrectomy 21.6%, total nephroureterectomy 33.3%, renal allotransplantation 82.8%, total cystectomy 96.2%). Mean homologous transfusion volume in these surveys was 982 ml. Two successful cases of autologous blood transfusion by the predeposit method or intraoperative collecting method are presented. Transfusion-associated adverse effects, especially viral infection and immunosuppression, were discussed and the value of autotransfusion was stressed. PMID- 2309585 TI - [A case of adrenal myelolipoma associated with adrenogenital syndrome]. AB - Myelolipoma is a benign non-functioning tumor, and the number of documented cases is increasing in recent years. We report a case of adrenal myelolipoma associated with adrenogenital syndrome. A 65-year-old woman presented with a complaint of abdominal discomfort. CT showed a mass with abundant fatty density in the left adrenal gland suggesting myelolipoma. She was small and thin. External genitalia had a female appearance, but showed type III abnormality in Prader's classification with clitoral hypertrophy. She had a history of primary amenorrhea. Endocrinological examination revealed marked increase in the 17 alpha hydroxyprogesterone (or 17-OHP) and pregnanetriol levels. On the basis of clinical features and laboratory values, simple virilizing type congenital adrenal hyperplasia due to 21-hydroxylase deficiency was made. The left adrenal tumor was surgically removed and histologically proved to be myelolipoma. Tumor uninvolved adrenal area adjacent to myelolipoma showed adrenocortical hyperplasia. To our knowledge, this is the first reported case of adrenal myelolipoma to be associated with congenital adrenal hyperplasia, due to 21 hydroxylase deficiency in Japan. The etiology of myelolipoma remains to be not clarified but our case suggests involvement of endocrine disorder in the development of this tumor. PMID- 2309586 TI - [Two cases of idiopathic retroperitoneal fibrosis effectively treated with steroid therapy]. AB - Two cases of idiopathic retroperitoneal fibrosis (IRPF) were reported. The first case, in a 72-year old man, was admitted for hydronephrosis with indistinct origin. Following percutaneous nephrostomy, biopsy of retroperitoneal tissue was performed, and IRPF was diagnosed. The treatment consisted of bilateral ureterolysis, intraabdominal transposition of ureters and oral administration of prednisolone for 3 months. The second case, in a 51-year-old woman, was admitted for the evaluation of severe azotemia. As ovarian carcinoma and its ureteral invasion was suspected, simple hysterectomy and bilateral ovariectomy were performed. Typical histological finding of IRPF was also observed. Oral administration of prednisolone has been continued for two years. Recurrence of IRPF has not been observed in these two cases for over two years. PMID- 2309587 TI - [A case of acute focal bacterial nephritis]. AB - Acute focal bacterial nephritis refers to a renal mass caused by acute focal infection. We report a case of acute focal bacterial nephritis, herein. The case was in a 56-year-old woman, who was hospitalized with the chief complaint of left flank pain, chills and fever. Intravenous pyelography suggested the presence of a mass in the upper pole of the left kidney. Ultrasonography showed a hypoechoic mass, CT scan revealed a round, low density mass. Antibiotic therapy resulted in resolution of symptoms, and a follow-up CT scan and ultrasonography showed complete resolution of the renal mass. PMID- 2309588 TI - [Two case reports of hydronephroureterosis associated with complete double pelvis ureter accompanied by pyuria and hematuria]. AB - We report two cases of hydronephroureterosis of the upper moiety in the complete duplex kidney disclosed by urological examination for pyuria and hematuria. The first case was in a 64-year old female and the second case was in a 68-year old female. Urinary incontinence was not seen in either case. Heminephrectomy was performed because the upper moiety was non-functioning and the upper ureter opened at the vesical neck in these cases. The postoperative course was uneventful. PMID- 2309589 TI - [Bladder augmentation in three patients with contracted bladder caused by neurogenic bladder]. AB - Three patients with contracted bladder caused by neurogenic bladder underwent ileocystoplasty. The primary diagnosis was meningomyelocele for all of them. The operative procedure adopted was Goodwin's Cup-patch method. All cases have obtained increased bladder capacity with improvement of bladder compliance and have been free from urinary incontinence. They were followed up by using clean intermittent self catheterization. Ileocystoplasty combined with clean intermittent self catheterization offers a successful method in patients with contracted bladder caused by neurogenic bladder. PMID- 2309590 TI - [A trial of the bladder assist device (BLADMAN) on Kock continent ileal urinary reservoir]. AB - A patient, who underwent total cystectomy and urinary diversion with the Kock pouch, was trained to use the Bladder Assist Device (BLADMAN) to augment the Kock continent ileal urinary reservoir. BLADMAN is a device to provide an intermittent drainage system, which simulates the normal periodic filling and emptying of the bladder of a patient with indwelling catheter. On the 16th day after starting the pouch augmentation with BLADMAN, the pouchgram of the patient revealed a pouch capacity of 450 ml. BLADMAN is considered to be a useful device for the augmentation of Kock continent ileal reservoir. PMID- 2309591 TI - [Atresia hymenalis with acute urinary retention: a case report]. AB - We report a case of atresia hymenalis in a 14-year-old girl presenting with a clinical symptom of acute urinary retention. On physical examination she was found to have a lower abdominal mass and an imperforate bulging hymen. She underwent hymenal incision, and subsequently the symptom disappeared. It is very uncommon for atresia hymenalis to manifest itself with acute urinary retention as the first clinical sign, but we should consider this disease if a pubertal girl seeks medical opinion for acute urinary retention. PMID- 2309592 TI - PTCA of the left coronary artery when the right coronary artery is chronically occluded. AB - Angioplasty of the left coronary artery was undertaken in 65 patients with a chronic total occlusion of the right coronary artery (CLOSED RCA) and in 105 patients with no significant disease in the right coronary artery (OPEN RCA). No patient had attempted dilatation of the right coronary artery. CLOSED RCA versus OPEN RCA patients differed with respect to presence of poor left ventricular (LV) function (12% versus 4%, p = 0.07), number of stenoses per patient (2.2 versus 1.8, p less than 0.05), and stenoses in both left anterior descending and left circumflex artery (39% versus 23%, p less than 0.05). Procedural complications were low for both CLOSED RCA (one death) and OPEN RCA (one emergency bypass surgery) patients. At late follow-up (mean = 17 months), there was no difference in survival between CLOSED RCA and OPEN RCA patients (95% versus 93%, p = NS). Late cardiac events (death, bypass surgery, or myocardial infarction) occurred in 26% of CLOSED RCA patients and in 16% of OPEN RCA patients (p = ns). The absence of angina at follow-up was more frequent in OPEN RCA compared with CLOSED RCA patients (84% versus 61%, p less than 0.01). Angioplasty of the left coronary artery can be performed in CLOSED RCA patients without excessive procedural risk; however, at follow-up continued anginal symptoms are common. PMID- 2309593 TI - Short- and long-term outcome of percutaneous transluminal coronary angioplasty in chronic dialysis patients. AB - Accelerated atherosclerosis occurs in chronic renal failure. The role of percutaneous transluminal coronary angioplasty (PTCA) in chronic renal failure patients requiring dialysis has not been characterized. We studied 17 chronic dialysis patients requiring PTCA over a 6-year period. Their mean age was 60 years, four were diabetic, eight had severe hypertension, and seven had unstable angina. Angiographic success was achieved in 47 of 49 (96%) stenoses attempted, including multivessel PTCA in 12 patients. There was one procedural death, two non-Q wave myocardial infarctions following PTCA, and one additional in-hospital noncardiac death. The 15 survivors were asymptomatic on discharge (mean stay 11 days), but recurrent angina developed within 6 months in 12 patients. Angiography in 11 of these 12 patients demonstrated restenosis of 26 of 32 (81%) dilated sites. Repeat PTCA in six patients was followed by return of angina in four patients with restenosis in 11 of 12 sites. Bypass surgery was ultimately performed in four patients with long-term angina relief. During follow-up (mean 20 months), seven patients died (five from chronic renal failure, two cardiac deaths). Thus although PTCA in chronic dialysis patients is technically feasible and provides relief of angina, aggressive restenosis limits the long-term benefit. Coronary bypass surgery may be the preferred therapy for this unique patient group. PMID- 2309594 TI - ST deviation in right chest leads V3R to V7R during percutaneous transluminal coronary angioplasty. AB - ST elevation in right chest leads during evolving inferior myocardial infarction indicates right ventricular involvement. Theoretically, such changes may be due to reversible or irreversible myocardial ischemia. Whether similar ST elevations can be recorded in patients with myocardial ischemia without infarction is unknown. To clarify this, right chest leads V3R to V7R were recorded during percutaneous transluminal coronary angioplasty in 43 patients who had a total of 45 arteries dilated. Balloon occlusion of the right coronary artery caused transient ST elevation, whereas closure of the left anterior descending coronary artery or the left circumflex artery was associated with transient ST depression. These findings were 100% discriminative in leads V5R and V6R. Furthermore, ST elevation greater than or equal to 1 mm in one or more of leads V4R to V7R was seen only when the right coronary artery was occluded. Thus transient myocardial ischemia without infarction may cause ST elevation in the right chest leads and ST elevation greater than or equal to 1 mm in one or more leads V4R to V7R is seen exclusively with occlusion of the right coronary artery. PMID- 2309595 TI - Coronary heart disease in Massachusetts: the years of change (1980-1984). AB - During this decade, diagnosis and treatment of coronary heart disease (CHD) have become far more aggressive and invasive than in prior decades. This study documents rates of hospitalization, use of various treatment options, a case fatality in the state of Massachusetts during 4 of the first 5 years of this decade (1980, 1982, 1983, and 1984). The data base was that of the Massachusetts Health Data Consortium (MHDC), covering all hospital discharges in the state, a total of 3.8 million discharge records for this period. Of these, about 190,000 (5%) fell into two active symptomatic categories of CHD: chronic active coronary disease (CACD) and acute myocardial infarction (AMI). Total hospitalization rate for these CHD categories increased by 17%; this was due both to an increased rate of hospital transfers (or readmissions) and to a larger cohort of patients under care. The case fatality rate for hospitalized CHD decreased approximately 16%, from 9.7% (1980) to 8.1% (1984). In CACD the frequency of coronary angiography (CA) rose; the use of percutaneous transluminal coronary angioplasty (PTCA) increased much faster than the rate of coronary artery bypass grafting (CABG), with a resultant increase in PTCA as a fraction of total interventions. Similar findings were recorded for AMI, but with much more marked changes, the total intervention rate increasing almost twenty-fold from 1980 to 1984. The statewide mortality rate for hospitalized CHD patients remained essentially unchanged at 71 to 74 hospital deaths per 100,000 population. PMID- 2309596 TI - Effect of stenosis on exercise-induced dilation of large coronary arteries. AB - The effects of a flow-limiting stenosis on external circumflex coronary arterial diameter during treadmill exercise were studied in 10 instrumented dogs. Coronary arterial diameter was measured by sonomicrometry proximal to the stenosis producing hydraulic occluder so that the effects of a post-stenotic pressure drop were excluded. With no stenosis, heart rate increased (116 +/- 7 to 183 +/- 10 beats/min, p less than 0.001), aortic pressure increased (97 +/- 3 to 105 +/- 5 mm Hg. p less than 0.005), circumflex coronary blood flow increased (48 +/- 8 to 72 +/- 8 ml/min, p less than 0.001), and circumflex coronary diameter increased (3.82 +/- 0.29 to 3.93 +/- 0.27 mm, p less than 0.01). In the presence of a flow limiting stenosis, heart rate increased (120 +/- 6 to 176 +/- 9 beats/min, p less than 0.001), aortic pressure did not change significantly (95 +/- 4 to 92 +/- 4 mm Hg), circumflex coronary blood flow increased slightly (39 +/- 8 to 46 +/- 9 ml/min, p less than 0.005), and circumflex coronary arterial diameter did not change significantly (3.78 +/- 0.29 to 3.80 +/- 0.28 mm). The stenosis prevented the increase in aortic pressure, blunted the increase in circumflex coronary blood flow (24 +/- 4 versus 7 +/- 2 ml/min, p less than 0.005), and prevented the increase in circumflex coronary arterial diameter. Therefore normal coronary arteries dilated during exercise and a flow-limiting stenosis prevented exercise induced coronary dilation proximal to the stenosis, possibly due to both the failure of aortic pressure to increase and less flow-induced endothelium dependent dilation. PMID- 2309597 TI - Beneficial effect of residual flow to the infarct region on left ventricular volume changes after acute myocardial infarction. AB - To determine the relationship between alterations in left ventricular (LV) volumes and residual flow to the infarct region after myocardial infarction (MI), 57 patients with a first acute transmural MI underwent two-dimensional echocardiography within 48 hours of infarction and after 1 month. A reduction in ST segment elevation by greater than or equal to 35% of the peak value of ST segment elevation within the initial 6 hours was used as an indirect indicator for early reperfusion of the infarct-related artery (IRA). IRA patency and collateral circulation were assessed by coronary arteriography performed at 1 month. LV volumes increased in patients with a persistent ST segment elevation within the initial 6 hours of infarction and in those with a totally occluded IRA without collaterals. However, LV volumes were unchanged in patients with early reperfusion and in those who had subtotally occluded IRA or who had collateral circulation. LV dilation (greater than or equal to 20% increase in end-diastolic volume) occurred less often when early reperfusion and angiographically patent IRA or collateral supply to the infarct zone were present. This prospective study indicates that residual flow to the infarct region may exert a beneficial effect on LV volume changes after acute MI. PMID- 2309598 TI - Exercise-induced silent myocardial ischemia in patients with vasospastic angina. AB - To clarify the incidence and clinical characteristics of exercise-induced myocardial ischemia in patients with vasospastic angina, we performed exercise thallium computed tomography in 25 patients who had no significant coronary artery stenosis greater than 70%. Coronary artery spasm was documented by coronary angiography in all patients. Eleven patients (44%) developed exercise induced perfusion defects, but only four of them had anginal pain (36%). Diltiazem (90 mg, administered orally) prevented the development of exercise induced perfusion defects in all patients. Multivessel coronary spasm was documented by coronary angiography in 11 patients, and nine of them (82%) showed exercise-induced perfusion defects (p less than 0.05). CONCLUSION: (1) Exercise induced myocardial ischemia was demonstrated in 44% of patients who had vasospastic angina without fixed coronary stenosis, and 64% of them were asymptomatic. (2) Patients with multivessel spasm had a greater prevalence of exercise-induced myocardial ischemia than those with single-vessel spasm. PMID- 2309599 TI - Exercise-induced silent myocardial ischemia: evaluation by thallium-201 emission computed tomography. AB - Factors associated with silent myocardial ischemia (SMI) during exercise testing were studied by means of thallium-201 emission computed tomography (ECT) in 471 patients. Coronary angiography was done in 290, of whom 167 were found to have significant coronary artery disease (CAD). Exercise-induced ischemia and its severity were defined with ECT. During exercise 108 (62%) of 173 patients with ischemia and 57 (50%) of 115 with ischemia and angiographically documented CAD had no chest pain. One third of the patients showed an inconsistency between scintigraphic ischemia and ischemia ST depression. Age, sex, prior myocardial infarction, and diabetes mellitus were not related to SMI. Patients with SMI had less severe ischemia despite a higher peak double product compared to those with painful ischemia. Among 91 with prior myocardial infarction and exercise-induced ischemia, 51 with periinfarction ischemia had a higher frequency of SMI than did 14 with ischemia remote from the prior infarct zone despite similarities in the severity of ischemia. In conclusion, factors localized within ischemic myocardium such as less severe ischemia or adjacency to a prior infarct made SMI more prevalent. PMID- 2309600 TI - Atrial septal defect resulting from mitral balloon valvuloplasty: relation of defect morphology to transseptal balloon catheter delivery. AB - Percutaneous balloon mitral valvuloplasty has been shown to be an effective means of reducing mitral valve gradient and increasing mitral valve area in patients with mitral stenosis. Most techniques currently employed for performing this procedure involve delivery of one or two balloon valvuloplasty catheters through the interatrial septum en route to the mitral valve orifice. To determine the morphology of the resultant atrial septal defect (ASD), particularly as a function of the technique employed, we performed a series of in vitro experiments designed to simulate a variety of technical approaches. Ninety-eight experiments in total were performed in 19 normal adult hearts obtained in the fresh, nonpreserved state at necropsy. Transseptal delivery and withdrawal of two conventional, elliptical balloon catheters through two, individual septostomy sites was found to produce the largest ASD (combined area of two defects = 21.4 +/- 2.2 mm2). The defect resulting from transseptal delivery and tandem withdrawal of two elliptical balloon catheters through a single septostomy site measured 14.8 +/- 1.1 mm2, significantly (p = 0.0043) smaller than that produced by two septostomies. Transseptal delivery and withdrawal of a single, segmentally inflating (Inoue) balloon catheter produced a defect of intermediate size (17.5 +/- 1.2 mm2). ASD size was exacerbated by improper balloon withdrawal compared with tandem withdrawal of two completely deflated balloon catheters. Simultaneous withdrawal of two completely deflated balloon catheters through the same septostomy site increased ASD size from 14.8 +/- 1.1 mm2 to 23.6 +/- 2.3 mm2 (p = 0.0004). Simultaneous withdrawal of two incompletely deflated balloon catheters further increased ASD size to 45.8 +/- 2.6 mm2 (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309601 TI - Participation of a concealed nodoventricular fiber in the genesis of paroxysmal tachycardias. AB - An unusual form of tachycardia circuit is described. The circuit incorporates a concealed nodoventricular fiber that conducts in a retrograde path, connects the atrioventricular node and the right ventricle, and also includes the distal portion of the atrioventricular node, the His-Purkinje system, and the ventricle. The study patient was first seen with paroxysmal tachycardias of normal QRS duration, complete right bundle branch block, and complete left bundle branch block. Electrophysiologic studies disclosed poor anterograde atrioventricular nodal conduction with a block proximal to His deflection that occurred at an atrial paced cycle length of 600 msec with no ventriculoatrial conduction. The tachycardias were inducible with two ventricular extrastimuli, had a His deflection that preceded each QRS complex and an HV interval identical to that during sinus rhythm, and revealed ventriculoatrial dissociation. Tachycardia with QRS patterns of right bundle branch block had a cycle 30 to 35 msec longer than tachycardias with either normal QRS duration or complete left bundle branch block. Tachycardias could be entrained by appropriate right ventricular pacing at rates slightly faster than the rate of tachycardia. Tachycardias could be terminated abruptly by an intravenous bolus of either adenosine triphosphate or verapamil. PMID- 2309602 TI - Comparative accuracy of the vectorcardiogram and electrocardiogram in the localization of the accessory pathway in patients with Wolff-Parkinson-White syndrome: validation of a new vectorcardiographic algorithm by intraoperative epicardial mapping and electrophysiologic studies. AB - The scalar electrocardiograms (ECGs) and vectorcardiograms (VCGs) of 41 patients with Wolff-Parkinson-White (WPW) syndrome were used to compare the accuracy of these techniques in the identification of the site of preexcitation. The location of the accessory pathway (AP) was determined by endocavitary electrophysiologic studies in all patients and the location was confirmed during intraoperative epicardial mapping in 28 of them. The ECGs were classified according to Gallagher's criteria and with Milstein's algorithm, whereas the VCGs were classified according to a new two-step algorithm. The presence of multiple accessory pathways and coexisting myocardial infarctions were major limitations in both the VCG and ECG classification procedures. In patients with a single accessory pathway, three AP localizations (right free ventricular wall, posterior, or left free ventricular wall) were identified with the first step of the VCG algorithm, with an overall sensitivity (96.5%), specificity (90.7%), and positive predictive values (80%) that were greater than those obtained with the ECG Milstein algorithm (77.1%, 91.5%, and 75%, respectively). The second step of the VCG algorithm made it possible to identify an AP location in one of the following sites: anterior right, lateral right, posterior right, posterior left, lateral left, or anterior left ventricle. The overall sensitivity, specificity, and positive predictive values were greater for the second step of the VCG algorithm than for the ECG criteria proposed by Gallagher (43.6% versus 39.3%, 92.1% versus 87.4%, and 51.5% versus 33.3%, respectively). It was concluded that the VCG seems to be more specific and sensitive than the ECG in the identification of the preexcitation site and should be given preference in the initial evaluation of the WPW syndrome. PMID- 2309603 TI - Effects of multipolar electrode radiofrequency energy delivery on ventricular endocardium. AB - This study examined the effects of radiofrequency energy applied in a bipolar fashion with single as compared with multiple sequential applications at the canine endocardium. In this closed-chest model, radiofrequency energy (750 kHz) was delivered between two adjacent poles of an electrode catheter. Single applications were performed at distinct sites in the left (n = 30) and right ventricles (n = 29) of 13 normal dogs. A multiple sequential technique, which enlarges the ablated endocardial surface, was applied in the left (n = 13) and right ventricles (n = 4) of seven normal dogs and six dogs with remote myocardial infarction. Single applications (199 +/- 200 joules) resulted in lesions with a volume of 0.12 +/- 0.06 cm3 (range 0.03 to 0.31 cm3) and an endocardial surface area of 0.29 +/- 0.15 cm2 (range 0.06 to 0.63 cm2). Changes at the catheter/tissue interface led to a rise in impedance, restricting further enlargement of the necrosis. Sequential delivery of radiofrequency energy between poles 1 and 2, 2 and 3, and 3 and 4 of a quadripolar electrode catheter repeated 9 to 11 times in slightly different positions allowed a cumulative energy of 6571 +/- 3857 joules to be applied to the endocardium, resulting in a lesion volume of 0.84 +/- 0.38 cm3, with an endocardial lesion surface area of 3.7 +/- 1.2 cm2 (range 2.9 to 5.1 cm2). Histologically, all radiofrequency lesions were restricted to the endocardium/subendocardium with a small border zone of injury. Aggressive stimulation techniques did not induce ventricular tachycardia in any of the dogs before and 19 +/- 11.4 days after multiple sequential ablations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309604 TI - Left ventricular filling at elevated diastolic pressures: relationship between transmitral Doppler flow velocities and atrial contribution. AB - The relationship between transmitral Doppler blood flow velocities and atrial contribution to left ventricular (LV) filling was investigated in seven open chest dogs. At LV filling pressures greater than 15 to 20 mm Hg, LV volume approaches a maximum. Thus we hypothesized that when LV pressure before the onset of atrial systole exceeds this level, the atrial contribution would decrease and the ratio between peak early (E) and atrial-induced (A) mitral velocities would increase. Atrial contribution was measured as LV diameter increase during atrial contraction expressed as a percentage of the total LV diameter change during diastole (sonomicrometry). When left ventricular end-diastolic pressure (LVEDP) was progressively increased from 10 +/- 1 (mean +/- standard deviation) to 28 +/- 3 mm Hg by intravenous saline solution, the atrial contribution decreased from 34 +/- 14% to 8 +/- 10% (p less than 0.001). Concomitantly the A velocity decreased from 39 +/- 7 to 24 +/- 8 cm.sec-1 (p less than 0.01), and the E/A ratio increased from 1.8 +/- 0.3 to 3.6 +/- 1.5 (p less than 0.001). The E/A ratio and the atrial contribution were constant until LVEDP exceeded 17 to 20 mm Hg, at which level marked changes in both parameters were noted. Thus when LV filling pressure was increased, the E/A ratio increased, indicating a filling shift towards early diastole. The reduced atrial contribution during increased preload was explained by the curvilinear shape of the LV pressure-volume curve. At markedly elevated filling pressures, near-maximum LV diameter was achieved before atrial contraction; hence the atrial contribution decreased and the E/A ratio increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309605 TI - Significance of laminar systolic regurgitant flow in patients with tricuspid regurgitation: a combined pulsed-wave, continuous-wave Doppler and two dimensional echocardiographic study. AB - To define the significance of laminar systolic tricuspid regurgitant (TR) flow, pulsed-wave and continuous-wave Doppler (PWD, CWD), and two-dimensional and M mode echocardiography (2-DE, M-mode) were performed in 68 patients with TR, which included five patients with tricuspid valvectomy. The pattern of TR flow (laminar versus turbulent), TR severity (the distance that the regurgitant flow extended into the right atrium [1+ to 4+ as measured by PWD]), the peak flow velocity of TR by CWD, the presence or absence and the amount of systolic tricuspid cusp separation by 2-DE, and the dimension of the right ventricle and the inferior vena cava by M-mode, were assessed. A laminar pattern of TR flow in systole was obtained in 21 patients, five of whom had undergone tricuspid valvectomy. Fourteen of 21 had visible tricuspid cusp separation in systole on 2-DE; of the seven who had no visible tricuspid cusp separation during systole, five had undergone tricuspid valvectomy. All 47 patients with a turbulent pattern of TR flow had no visible systolic tricuspid cusp separation. Severe 4+ TR was present in 14 of 21 (67%) patients with laminar TR flow and in 4 of 47 (9%) patients with turbulent TR flow (p less than 0.001). The peak flow velocity of TR in patients with laminar TR flow (2.0 +/- 0.7 m/sec) was lower (p less than 0.001) than in those with turbulent TR flow (3.1 +/- 0.7 m/sec).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309606 TI - Verapamil but not nifedipine impairs left ventricular function during exercise in hypertensive patients. AB - Calcium antagonists are popular therapeutic agents in the treatment of systemic hypertension. Although these agents have similar antihypertensive efficacy, they have varied effects on left ventricular function at rest in hypertensive patients. The effect of different calcium antagonists on left ventricular function during exercise and on exercise performance in patients with hypertension, however, is less clear. Fifteen patients with essential hypertension (diastolic blood pressure = 95 to 110 mm Hg) were enrolled in a placebo-controlled, single-blinded crossover study comparing nifedipine with verapamil for rest/exercise heart rate and blood pressure, exercise performance, and rest/exercise left ventricular function. Each drug was titrated to achieve resting diastolic pressures less than 90 mm Hg. All patients underwent maximal exercise testing and rest/exercise gated radionuclide ventriculography at the end of 3-week placebo, nifedipine, and verapamil treatment periods. Both calcium antagonists significantly reduced blood pressure at rest and during exercise compared with placebo. Neither calcium antagonist altered resting heart rate; however, both verapamil and nifedipine significantly reduced heart rate at maximal exercise. Verapamil but not nifedipine impaired left ventricular peak emptying rate and left ventricular peak filling rate during exercise but not at rest. Neither verapamil nor nifedipine, however, significantly altered rest or exercise global left ventricular ejection fraction (LVEF) compared with placebo. There was a trend, however, for impairment in the LVEF response to exercise (delta LVEF) in the verapamil treatment group. Exercise capacity was not significantly altered by either calcium antagonist compared with placebo. Thus verapamil but not nifedipine impairs left ventricular function during exercise in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309607 TI - Successful percutaneous balloon valvuloplasty of a stenotic tricuspid bioprosthesis. PMID- 2309608 TI - Delayed recovery of revascularized myocardium after referral for cardiac transplantation. PMID- 2309609 TI - Is dipyridamole-thallium imaging preferable to submaximal exercise thallium testing for risk stratification after thrombolysis? PMID- 2309610 TI - Congenital aneurysm of the right coronary artery with fistulous connection to the right atrium. PMID- 2309611 TI - Acute coronary thrombosis following head trauma in a young man. PMID- 2309612 TI - Coronary artery-to-left ventricle communication with abnormal regional coronary flow demonstrated by ultrafast computed tomography. PMID- 2309613 TI - The echocardiographic recognition of an atrial myxoma vegetation. PMID- 2309614 TI - Anterolateral myocardial rupture following mitral valve replacement: transesophageal echo documentation of ischemic etiology. PMID- 2309615 TI - Noninvasive evaluation of pulmonary artery systolic pressures during dynamic exercise by saline-enhanced Doppler echocardiography. PMID- 2309616 TI - Aortic thrombosis and peripheral embolization after thoracic gunshot wound diagnosed by transesophageal echocardiography. PMID- 2309617 TI - Atypical creatine kinase MB isozyme in an elderly patient without evidence of myocardial infarction or underlying malignancy. PMID- 2309618 TI - Asynchronous leaflet closure in the normally functioning bileaflet mechanical valve. PMID- 2309619 TI - Cholesterol pericarditis and cardiac tamponade with congenital hypothyroidism in adulthood. PMID- 2309620 TI - The effects of exercise during viremia on the signal-averaged electrocardiogram. PMID- 2309621 TI - Myocardial hibernation and "embalmment". PMID- 2309623 TI - A symposium: Hormone-electrolyte interactions in congestive heart failure. Atlanta, Georgia. Proceedings. PMID- 2309622 TI - Appraisal of false positive results in nuclear cardiac imaging. PMID- 2309624 TI - Interaction of diuretics and electrolytes in congestive heart failure. AB - Diuretic drugs have been the mainstay of treatment for heart failure. Specific elucidation of the effects of diuretics on electrolytes, however, has been difficult, since the heart failure state itself may alter the electrolyte balance. Nevertheless, it is noteworthy that the natriuretic effect of loop diuretics is greater in edematous patients than in healthy volunteers; yet, the initial kaliuresis is minimal--perhaps because aldosterone levels are low. With continued treatment (or after the edema has been cleared), however, the natriuretic action of loop diuretics is less than that seen in controls, but loss of potassium occurs. The addition of a thiazide to a loop diuretic enhances its natriuretic effect. Both loop and thiazide diuretics can induce depletion of magnesium. Potassium-sparing diuretic drugs augment the natriuresis induced by loop or thiazide diuretics but limit or prevent the loss of potassium or magnesium in the urine, at least in the short term. However, potassium-sparing diuretics can exacerbate the development of hyponatremia. PMID- 2309625 TI - Interaction of the sympathetic nervous system and electrolytes in congestive heart failure. AB - Congestive heart failure is characterized by both disturbances in electrolyte homeostasis and neuro-hormonal regulation. Total body potassium is reduced, and this reduction bears a modest relation to activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Patients with decompensated heart failure show increases in both plasma epinephrine and plasma norepinephrine, whereas patients with chronic stable heart failure usually have an increase only in plasma norepinephrine. High levels of circulating epinephrine may contribute to the development of hypokalemia by activating skeletal muscle and liver membrane beta 2-adrenergic receptors, which in turn stimulate intracellular cyclic adenosine monophosphate to activate the membrane-bound Na+K(+)-adenosine triphosphatase pump. The net result is that potassium flux across the cell membrane from the extracellular to the intracellular space increases, setting the stage for hypokalemia and possibly serious ventricular arrhythmias. Other mechanisms that may contribute to the development of hypokalemia in heart failure include the kaliuresis brought on by excessive levels of aldosterone. Moreover, it is likely that the activity of facilitated by concomitant activation of the renin-angiotensin system. Increased sympathetic nerve activity may then release additional renin from the kidney (by way of a beta 2-adrenergic mechanism). Therefore, both the sympathetic nervous system and the adrenal medulla may interact to cause hypokalemia in patients with heart failure. Because hypokalemia is known to predispose patients to ventricular arrhythmias, it may be prudent to aggressively maintain serum potassium levels in patients with heart failure in the range of 4 to 5 mEq/liter. PMID- 2309626 TI - Influence of anterograde flow in the infarct artery on the incidence of late potentials after acute myocardial infarction. AB - In patients after myocardial infarction, survival is influenced by the presence or absence of anterograde flow in the infarct artery, and late potentials on signal-averaged electrocardiography identify those at risk for tachyarrhythmias and sudden death. To assess the frequency of late potentials in survivors of first infarction, coronary arteriography and signal-averaged electrocardiography were performed in 109 subjects (64 men, 45 women, aged 30 to 77 years), 49 with (group I) and 60 without (group II) anterograde flow in the infarct artery. The groups were similar in age, sex, infarct artery, severity of coronary artery disease and left ventricular function. However, only 4 (8%) of group I had late potentials, whereas 24 (40%) of group II had late potentials (p less than 0.001). Thus, anterograde flow in the infarct artery after myocardial infarction is associated with a low incidence of late potentials on signal-averaged electrocardiography, whereas the absence of anterograde flow is more often associated with late potentials. PMID- 2309627 TI - Early estimation of risk by echocardiographic determination of wall motion index in an unselected population with acute myocardial infarction. AB - In a prospective series of 201 consecutive patients with creatine kinase-MB- documented acute myocardial infarction (AMI), postadmittance and predischarge echocardiographic wall motion indexes (WMI) were determined (median 45 hours vs 14 days after AMI). No significant change of left ventricular systolic performance was found between postadmittance and predischarge examinations in 179 survivors (WMI 1.3 +/- 0.4 vs 1.4 +/- 0.4, p greater than 0.05). Hospital mortality was 11% (22 of 201), cumulated 2-month mortality 15% (31 of 201) and cumulated 1-year mortality 26% (52 of 201). Mortality increased rapidly with decreasing left ventricular function as determined by WMI. When early WMI was less than 1.0, 1-year mortality was 51% (28 of 55) versus 8% (7 of 83) when WMI was greater than 1.3 (p less than 0.0001). Ventricular fibrillation (n = 24) and cardiogenic shock (n = 27) carried a much better prognosis when WMI showed good left ventricular function. When WMI was less than 1.0, 1-year mortality was 83% (10 of 12) versus 93% (13 of 14) in ventricular fibrillation and cardiogenic shock, respectively, whereas it was 0% (0 of 4) versus 33% (2 of 6) when WMI was greater than 1.3. In 15% of patients major discrepancies between early Killip class and WMI were noted. WMI showed much smaller fluctuations during the hospital course of AMI than did Killip class and appeared to be a more stable prognostic marker. Large-scale, early risk stratification by echocardiography has now become available and appears to facilitate a rational, individualized discharge policy in the coronary care unit and to provide an improved basis for randomization of patients in controlled studies aimed at tailoring new treatment in AMI. PMID- 2309628 TI - Value of right-sided cardiac catheterization in patients undergoing left-sided cardiac catheterization for evaluation of coronary artery disease. AB - The value of right-sided cardiac catheterization was assessed prospectively in 200 patients undergoing left-sided catheterization for evaluation of known or suspected coronary artery disease. Before catheterization, data from right-sided catheterization was not felt to be necessary for clinical management. There were 6 +/- 2 extra minutes of procedure time and 86 +/- 63 extra seconds of fluoroscopy time used. Abnormalities were detected in 69 (35%) patients. These findings were unexpected in 37 of these patients and in 3 patients, further evaluation was prompted. However, management was altered in only 3 (1.5%) patients as a result of data obtained by right-sided catheterization. In conclusion this additional procedure rarely adds clinically useful information about patients undergoing left-sided catheterization and angiography for coronary artery disease without a clinical indication for right-sided catheterization. PMID- 2309629 TI - Value of electrophysiologic testing in patients with previous myocardial infarction and nonsustained ventricular tachycardia. Philadelphia Arrhythmia Group. AB - Previous studies of the value of electrophysiologic studies in patients with nonsustained ventricular tachycardia (VT) have been hampered by the inclusion of a small number of patients with various types of heart disease. This retrospective study was designed to assess the value of programmed stimulation in 205 asymptomatic patients who had had an acute myocardial infarction greater than 1 month before study. Inclusion was based on 24-hour Holter monitoring during which patients had to manifest greater than or equal to 3 consecutive ventricular beats at a rate greater than 135 beats/min. Forty-seven (23%) patients had normal, 70 (34%) mildly impaired and 88 (43%) severely impaired left ventricular function. Programmed stimulation, using up to 3 extrastimuli, was used in each. Seventy-five patients (36%) were noninducible, 59 (29%) had nonsustained VT (less than 30 seconds), 67 (33%) had sustained monomorphic VT and 4 (2%) had either polymorphic VT or ventricular fibrillation. Eighty-two patients were not treated with antiarrhythmic drugs, 57 others were placed on a program selected empirically and 66 had therapy guided by electrophysiologic testing. Satisfactory follow-up information was gathered in 187 of the 205 patients, with a mean follow up of 18 months. One hundred forty-two patients are alive and well, 39 had sustained VT or sudden death and 6 others had a cardiac death. Only left ventricular function discriminated those who had a sustained arrhythmia or died from those who did not. Thus, programmed stimulation did not have independent predictive value in patients with nonsustained VT. However, definitive conclusions can be reached only with a large prospective study carried out in untreated patients. PMID- 2309630 TI - Effects of transdermal scopolamine on heart rate variability in normal subjects. AB - A decrease in cardiac parasympathetic tone is a recognized finding in patients with ischemic heart disease, sudden cardiac death and heart failure, correlating closely with disease severity and overall survival. To study the clinical potential of vagomimetic intervention, the effect of transdermal scopolamine on fluctuations in heart rate was studied in 32 healthy adult subjects using both time-domain (mean RR interval, standard deviation of the mean RR interval, mean of the differences between consecutive RR intervals) and frequency-domain measures (spectrum analysis of 128 consecutive RR intervals) of heart rate variability. After an exposure of 24 hours, transdermal scopolamine resulted in a significant increase in all indexes tested. The increase was most pronounced in the 0.25-Hz respiratory peak of the RR interval power spectrum, compatible with a strong vagomimetic mode of action of transdermal scopolamine. Results indicate that transdermal scopolamine may have potential merit as a selective vagotonic agent in certain patients with myocardial infarction, heart failure or ventricular arrhythmias. PMID- 2309631 TI - Programmed ventricular stimulation using up to two extrastimuli and repetition of double extrastimulation for induction of ventricular tachycardia: a new highly sensitive and specific protocol. AB - The sensitivity and specificity of a new protocol of programmed ventricular stimulation were evaluated in 71 consecutive patients who were divided into 2 groups: group 1 included 41 patients, of whom 25 had sustained ventricular tachycardia (VT) not associated with cardiac arrest and 16 had ventricular fibrillation (VF) not precipitated by any obvious factor; group 2 included 30 patients without demonstrable heart disease and no suspected or documented sustained ventricular tachyarrhythmias. The study consisted of a standard protocol (up to 2 extrastimuli given only once for each extrastimulus prematurity, 2 right ventricular sites and 3 basic pacing cycle lengths, as well as rapid ventricular pacing) in which double extrastimulation at the shortest coupling intervals that allowed ventricular capture was repeated 10 times. A stimulus current of 3 mA was used. Sustained ventricular tachyarrhythmias were induced in 23 of 25 (92%) patients who presented with sustained VT, 14 of 16 (88%) patients who presented with VF and 2 of 30 (7%) group 2 patients. Eighteen of 25 (72%) patients with sustained VT but only 4 of 16 (25%) with VF had arrhythmias inducible at "immediate" trials of single or double extrastimulation (p less than 0.01). Repetition of double extrastimulation increased the yield of inducible sustained ventricular tachyarrhythmia to 92% in patients with sustained VT (+20%, p = 0.14) and 75% (+50%, p = 0.013) in patients with VF. Rapid right ventricular pacing added a 13% increase in the overall yield in patients with VF. This new protocol of programmed ventricular stimulation has both high sensitivity (90%) and specificity (93%) for induction of sustained VT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309632 TI - Effects of upright posture on atrioventricular accessory pathway conduction. AB - The electrophysiologic effects of 45 degrees head-up tilt were studied in 19 patients with atrioventricular accessory pathways. Upright posture enhanced both anterograde and retrograde accessory pathway conduction when compared to the supine position: the anterograde block cycle length decreased from 374 +/- 52 ms (mean +/- standard error) (supine) to 303 +/- 33 ms (tilt) (p less than 0.05); anterograde effective refractory period decreased from 286 +/- 17 to 249 +/- 10 ms (p less than 0.05); retrograde block cycle length shortened from 331 +/- 36 to 291 +/- 35 ms (p less than 0.05); retrograde effective refractory period decreased from 312 +/- 26 ms to 274 +/- 15 ms (p less than 0.05). During induced atrial fibrillation the mean RR interval and the shortest RR interval between preexcited beats decreased approximately 10% with head-up tilt. During orthodromic reciprocating tachycardia, tachycardia cycle length shortened 15%. Tachycardia rate during electrophysiologic study in the head-up position more closely approximated the rate of clinical tachycardia than did the rate in the supine position. Head-up tilt significantly enhances anterograde and retrograde accessory pathway conduction, increases the rate of arrhythmias using an accessory pathway and may be clinically useful in the assessment of patients with an accessory pathway. PMID- 2309633 TI - Electrophysiologic effects and efficacy of cibenzoline on stimulation-induced atrial fibrillation and flutter and implications for treatment of paroxysmal atrial fibrillation. AB - The effects of intravenous cibenzoline (1.5 mg/kg) on atrial vulnerability and electrophysiology were assessed in 25 patients with documented paroxysmal atrial fibrillation (AF), in whom sustained (greater than 30 seconds) AF was induced by atrial stimulation with up to 2 extrastimuli and paced rates between 100 and 180 beats/min. In 7 patients AF persisted despite the application of cibenzoline, and in 8 patients the induction of sustained AF was prevented by cibenzoline. Intraatrial conduction time, flutter cycle length and shortest ventricular cycle length during AF were increased by cibenzoline (p less than or equal to 0.01). Sinus cycle length was decreased (p less than or equal to 0.05), whereas sinus node recovery time remained unchanged. The effective refractory period of the right atrium was not significantly affected. Eight patients with frequent episodes of paroxysmal AF received oral cibenzoline for control of paroxysmal AF irrespective of the efficacy of intravenous cibenzoline. Prevention of stimulation-induced AF predicted successful treatment of paroxysmal AF (p = 0.018). Cibenzoline could be effective in the treatment of atrial arrhythmias, and selection of an antiarrhythmic therapy for recurrent AF seems to be useful. PMID- 2309635 TI - Percutaneous balloon mitral valvuloplasty by retrograde left atrial catheterization. AB - A new technique was developed for percutaneous mitral valve balloon valvuloplasty, using a retrograde approach to the left atrium via the left ventricle. A newly designed externally steerable guiding catheter is used for the introduction of 1 or 2 guidewires to the left atrium and the balloon catheters are advanced along these guidewires into the mitral orifice. The technique was used successfully in 10 adult patients with rheumatic mitral stenosis. After the procedure there was a significant reduction in mitral valve pressure gradient and an increase in the mitral valve area in all cases. There were no serious complications during or after the procedure. This technique should prove to be a useful nonsurgical treatment for mitral stenosis and could provide an alternative to the transseptal method. PMID- 2309634 TI - Relation of moderate alcohol consumption and risk of systemic hypertension in women. AB - The relation between alcohol consumption and the risk of development of hypertension was studied among 58,218 US female registered nurses aged 39 to 59 years who were free of diagnosed systemic hypertension and other major diseases. In 1980, all of these women completed an independently validated dietary questionnaire, which included use of alcoholic beverages. During 4 years of follow-up, 3,275 women reported an initial diagnosis of hypertension; validity of the self-report measure was demonstrated in a subsample. When compared to nondrinkers, women drinking 20 to 34 g of alcohol per day (about 2 or 3 drinks) had a significantly elevated relative risk of 1.4; the 95% confidence interval (CI) was 1.2 to 1.7 after adjustment for age and Quetelet's index. For women consuming greater than 35 g/day, the relative risk was 1.9 (95% CI 1.6 to 2.2). Adjustment for smoking and dietary variables did not alter these results. Independent significant associations were observed for the consumption of beer, wine and liquor. These prospective data suggest that alcohol intake of up to about 20 g/day does not increase the risk of hypertension among women, but beyond this level, the risk increases progressively. PMID- 2309636 TI - Growth of the human heart relative to body surface area. AB - To determine the growth rate of the human heart in relation to body surface area, normal data obtained by echocardiography and angiocardiography were analyzed with respect to changes in body size occurring between infancy and adulthood. Published data were used to determine the following for 7 theoretical subjects ranging in size from 0.2 m2 (normal newborn) to 2.2 m2 (large adult): average left ventricular (LV) end-diastolic diameter; aortic root diameter; right pulmonary artery diameter; aortic valve area; LV end-diastolic volume; and LV mass. Linear dimensions (LV, aortic and right pulmonary artery diameter) increased as a square root function of surface area and could not be described by a constant "index" of dimension to surface area. Aortic valve area was linearly related to surface area and equalled 3.4 cm2/m2 for subjects of all sizes. LV volume and mass were exponentially related to surface area. This study indicates that intracardiac areas may be indexed for body surface area, but that linear dimensions and volumes have a nonlinear relation to surface area and are more appropriately indexed by surface area to the 0.5 and 1.5 power, respectively. PMID- 2309637 TI - Significance of a lateral Q wave following first anterior wall acute myocardial infarction. PMID- 2309638 TI - Percutaneous transluminal coronary angioplasty in patients 80 years of age and older. PMID- 2309639 TI - Paradoxical paroxysmal nocturnal congestive heart failure as a severe manifestation of the pacemaker syndrome. PMID- 2309640 TI - Albumin and labile-protein serum concentrations during very-low-calorie diets with different compositions. AB - Circulating concentrations of albumin and the labile proteins prealbumin (PA) and retinol-binding protein (RBP) were evaluated over 20 d in five groups of obese patients. The patients were given four types of very-low-calorie diets (VLCDs) (less than 500 kcal/d) that provided different amounts of protein or carbohydrate (CHO) plus protein and a conventional 1200-kcal/d hypocaloric diet. Serum albumin concentrations did not vary significantly during any of the diets whereas PA and RBP remained unchanged only during the conventional 1200-kcal/d diet. Similar and significant decreases of serum PA and RBP were observed during the VLCDs studied. The molar ratio of RBP to PA did not vary during dieting. Thus, when less than 500 kcal/d are given, changes of serum short-half-life visceral proteins are not affected by either the addition of CHO to protein or the changes in protein intake. Moreover, serum albumin concentration and RBP/PA do not vary during VLCDs. PMID- 2309641 TI - Undernutrition among Bedouin Arab infants: the Bedouin Infant Feeding Study. AB - Two hundred seventy-four healthy Bedouin Arab newborns in 1981 were followed for 18 mo to examine the relationship between infant-feeding practices and growth during planned social change. Although wasting was not prevalent, the prevalence rate of stunting (less than or equal to -2 SDs) increased from 12% to 19% to 32% at 6, 12, and 18 mo, respectively. After multiple-logistic-regression adjustment for covariates, the odds ratio (OR) of stunting at 6 mo was reduced among infants breast-fed only or fed with supplement compared with weaned infants. Infant feeding practices were not associated with stunting in later infancy; however, those stunted at 6 mo had an OR of 13 of stunting at 12 mo and those stunted at 12 mo had an OR of 14 of stunting at 18 mo. In a multiple-linear-regression analysis, seasonality, duration of breast-feeding, hospitalized morbidity, and residual of height at 6 mo were negatively associated with daily average linear growth from 6 to 12 mo; these factors only explained 12% of the variation in daily linear growth. PMID- 2309642 TI - Energy utilization of breast-fed and formula-fed infants. AB - Breast-fed and formula-fed infants (n = 65) were studied at 1 and 4 mo of age to elucidate differences in energy utilization between feeding groups. Gross energy intake at 1 mo was comparable between groups but was statistically different at 4 mo. Weight, length, and weight gain were not different between groups. Energy expenditure 0-4 h postprandially did not differ between feeding groups. Sleeping metabolic rates (SMRs) were not different but minimal observable energy expenditures standardized by weight were lower among 4-mo-old breast-fed infants (p less than 0.03). No differences were found between feeding groups in thermic effect of feeding (TEF). Activity patterns revealed that breast-fed infants slept less than formula-fed infants (p less than 0.04). Disparities in energy intake observed between breast-fed and formula-fed infants at 4 mo of age did not result in statistically significant differences in growth rate, SMR, or TEF. PMID- 2309643 TI - Age-specific responsiveness of weight and length to nutritional supplementation. AB - Evaluation of the responsiveness of weight and length to supplementary feeding shows that the two periods of greatest response coincide with weaning (ages 3-6 mo) and peak incidence and duration of diarrheal disease (ages 9-12 mo). Analyses were done for seven consecutive nonoverlapping intervals comparing children randomly assigned to receive supplemental feeding from birth to age 36 mo or to serve as control subjects. Absolute responsiveness was greatest between ages 3-6 mo; supplemented infants grew 0.61 cm more and gained 162 g more than did unsupplemented infants (p less than 0.005). Relative to rates of growth, responsiveness was greatest between ages 9 and 12 mo (the period of peak diarrheal prevalence), followed by ages 3-6 mo (the period of weaning). Responsiveness to supplementation is thus directly related to age-dependent risk patterns for malnutrition. Targeting supplementation programs to coincide with periods of high nutritional risk should maximize their effectiveness in reducing malnutrition, though caution should be exercised to avoid disruption of breast feeding. PMID- 2309645 TI - Dietary-fish effects on serum lipids and apolipoproteins, a controlled study. AB - In Maastricht and Zeist, The Netherlands, and Tromso, Norway, a well-controlled study was performed on the effect of a fish-enriched diet on serum lipids, apolipoproteins A-1 and B, and fatty acid compositions of serum triglycerides and cholesterol esters. For 6 wk healthy male volunteers were given a daily dietary supplement consisting of 135 g mackerel paste (experimental group, n = 42) or meat paste (control group, n = 42). Dietary adherence was calculated on the basis of urinary excretion of a standard amount of lithium added to the supplements. Average compliance was 80%. Low-density-lipoprotein (LDL) and total serum cholesterol concentrations were unaffected. High-density-lipoprotein (HDL) cholesterol increased to a comparable degree in both groups. Triglyceride content of serum decreased in the fish group. Apolipoproteins A-1 and B (both in Maastricht subjects only) were only slightly affected. In the mackerel group the n-3 fatty acids increased significantly in serum cholesterol esters and triglycerides; the n-6 fatty acids decreased in cholesterol esters only. PMID- 2309644 TI - Dietary protein and nitrogen balance in lactating and nonlactating women. AB - Adaptive responses of body protein metabolism to dietary protein intakes of 1.0 g.kg body wt-1.d-1 were determined by nitrogen balance and urinary 3 methylhistidine excretion in lactating and nonlactating women. Despite higher energy intakes (p less than 0.04), lactating women had lower nitrogen balances compared with nonlactating postpartum and nulliparous women (p less than 0.001). Nitrogen losses in milk did not account entirely for these differences. Nitrogen balance showed linear (p less than 0.04) and quadratic (p less than 0.03) trends over time postpartum among the lactating women. Urinary 3-methylhistidine excretion also was reduced (p less than 0.05) in lactating compared with nonlactating women. These observations suggest that protein intakes of 1.0 g.kg body wt-1.d-1 in lactating women are associated with adaptive responses that promote the conservation of skeletal muscle protein stores and that currently recommended dietary protein allowances may be insufficient to meet the nutritional needs of well-nourished lactating women. PMID- 2309646 TI - Fish oils in hypertriglyceridemia: a dose-response study. AB - The effects of three supplemental doses of fish oil on plasma lipids, lipoproteins, and bleeding times were studied in ten hypertriglyceridemic patients. After a 3-wk baseline period each patient was given 15, 25, or 40 mL fish oil/d (containing 4.5, 7.5, and 12 g n-3 fatty acids) for three successive 6 wk periods, each separated by a 4-wk period of no supplementation. Plasma cholesterol concentrations decreased from 7.40 mmol/L to 6.35, 6.55, and 6.40 mmol/L with increasing doses of fish oil (p less than 0.01 vs baseline for each). Plasma triglyceride concentrations decreased from 6.10 mmol/L to 2.90, 2.80, and 2.35 mmol/L (p less than 0.01 vs baseline for each). Low-density-lipoprotein cholesterol concentrations increased significantly (by 23% and 28%) with the two higher doses, respectively. Bleeding times increased only with the largest dose. The lowest dose was the most hypolipidemic per gram n-3 fatty acids. PMID- 2309647 TI - Plasma and red blood cell carnitine and carnitine esters during L-carnitine therapy in hemodialysis patients. AB - Plasma and red blood cell (RBC) carnitine and acylcarnitines were determined in 20 hemodialysis (HD) patients during three different L-carnitine dosages (1, 5, and 15 mg/kg body wt), each for 3 mo. Before L-carnitine treatment, free carnitine was significantly lowered in plasma but elevated in RBCs compared with healthy subjects. Short-chain acylcarnitines were elevated in plasma and normal in RBCs. HD therapy decreased plasma free and acylcarnitines markedly but did not influence RBC values. Low-dose L-carnitine treatment normalized both plasma- and RBC-free carnitine. Dosages of 5 and 15 mg/kg body wt increased plasma and intracellular carnitine and carnitine esters impressively. Plasma and RBC carnitine fractions remained elevated even after a 6-wk washout period. Low-dose L-carnitine treatment is sufficient to correct disturbed plasma and RBC carnitine and carnitine esters of HD patients. Elevated RBC carnitine esters decreased very slowly, suggesting low RBC carnitine turnover. Carnitine overdosage should be prevented in those patients who benefit from carnitine therapy. PMID- 2309648 TI - Utilization for protein synthesis of leucine and valine compared with their keto analogues. AB - Fasting rats were given [3H]leucine plus [14C]2-ketoisocaproate or [3H]valine plus [14C]2-ketoisovalerate, plus 33 micromol of each compound. The ratio of 14C to 3H (R) in protein 6 h after injection of these isotopes is a measure of the extent to which extracellular keto acid, as compared with extracellular amino acid, serves as the source of the intracellular amino acid used for protein synthesis. R for 2-ketoisocaproate (KIC) vs leucine was 0.45 +/- 0.03 for whole body protein after oral injection and 0.83 +/- 0.02 after iv injection. R values for 2-ketoisovalerate (KIV) vs valine were similar. R, measured in the protein of various organs and in albumin, fibrin, and globin, varied more than twofold. We conclude that at least half of KIC and KIV given orally in this dosage is oxidized in splanchnic organs during first pass but that, nevertheless, these keto acids given orally serve as significant sources of the intracellular amino acids used for protein synthesis in most organs, particularly brain and heart. PMID- 2309649 TI - Questioning riboflavin recommendations on the basis of a survey in China. AB - Riboflavin status was surveyed in adults aged 35-64 y in 65 counties (two communes per county) in the People's Republic of China by erythrocyte glutathione reductase activity coefficients (EGRACs), by urinary excretion of riboflavin 4 h after the oral administration of 5 mg riboflavin (one commune per county), and by direct measurement of food intake over a 3-d period (one commune per county). EGRAC data were highly correlated between sexes (p less than 0.001) and between neighboring communes within the same county (p less than 0.001) and with riboflavin intake (p less than 0.001). The urinary-riboflavin-load test data were not correlated either with EGRAC or with riboflavin intake. Approximately 90% of the survey subjects were found to be deficient by Western and Chinese reference standards and allowances. Upon reconsideration of the Western experimental data originally used to establish these recommendations, it is suggested that riboflavin allowances are set too high both in China and in Western countries. PMID- 2309650 TI - Aging and vitamin B-6 depletion: effects on plasma pyridoxal-5'-phosphate and erythrocyte aspartate aminotransferase activity coefficients in rats. AB - Plasma pyridoxal-5'-phosphate (PLP) and erythrocyte aspartate aminotransferase activity coefficients were longitudinally determined in rats. Blood was obtained at weeks 0, 1, 2, 4, 6, 9, and 11 from rats initially aged 3 wk, 3 mo, 12 mo, and 23 mo (weeks 0, 1, 4, 6, and 9 only). The diet groups were ad libitum control (ALC), deficient (DEF), and pair-fed control (PF). Plasma PLP concentrations of controls were highest at 3 mo, intermediate at 3 wk and 12 mo, and lowest at 23 mo. When an additional group of 22-mo-old rats was fed a high-vitamin B-6 diet for 4 wk, their low baseline plasma PLP concentrations did not increase significantly. Plasma PLP decreased significantly within 1 wk and activity coefficients increased significantly by week 4 in all DEF rats. Depletion was most rapid and severe in the youngest DEF rats and least in 12-mo-old DEF rats. Mechanisms for the low plasma PLP control values and resistance to depletion in aged rats remain to be determined. PMID- 2309651 TI - Plasma ferritin concentrations in anemic children: relative importance of malaria, riboflavin deficiency, and other infections. AB - Anemia (hemoglobin less than 110 g/L) was documented in 36 children of both sexes aged 1-12 y who were divided into two groups: malaria and other infections. The control subjects were 10 children of similar age with no anemia and without any apparent infections. Plasma ferritin concentrations (median, range) were higher in the anemic patients (203 micrograms/L, 21-5000 micrograms/L) than in control children (52 micrograms/L, 25-239 micrograms/L) although ferritin concentrations in those with malaria were still within the normal range (99 micrograms/L, 21-205 micrograms/L). In the rest of the anemic group, five patients had plasma ferritin concentrations greater than 1000 micrograms/L. There was no difference in riboflavin status between control subjects and patients or between the two anemic groups. Severity of anemia was no different between the two anemic groups either. The data indicate that riboflavin deficiency makes no contribution to the infection-induced elevation in plasma ferritin and that the contribution of malaria is smaller than that of other unidentified factors. PMID- 2309652 TI - Intake, serum concentrations, and urinary excretion of manganese by adult males. AB - Nutritional status of manganese in 10 adult males was monitored through a 47-d period by measuring manganese in serum and urine and by chemically analyzing duplicate portions of all foods and beverages consumed on 3 d, with computer analysis of dietary records for 10 additional days. Subjects consumed 0.52-5.33 mg Mn/d; 50% of the time they consumed less than the 1980 Estimated Safe and Adequate Daily Dietary Intake for manganese. Subjects on average (+/- SEM) excreted 7.0 +/- 0.5 nmol Mn/g creatinine; their average serum manganese concentration was 19.3 +/- 1 nmol/L. These potential indices of manganese exposure were not correlated with the subjects' dietary intakes of manganese or other minerals. However, serum manganese concentrations tended to be elevated (p less than 0.064) in five subjects who consumed 15 mg chelated Mn/d for 7 d. PMID- 2309653 TI - Zinc, magnesium, copper, and protein concentrations in human saliva: age- and sex related differences. AB - Normal concentrations of trace elements in parotid saliva, supernatant- and sediment-mixed saliva, plasma, and hair were determined in 278 healthy adults grouped as young (18-29 y), middle-aged (30-64 y), and elderly (65-93 y). Age related increases (p less than 0.05) were observed in concentrations of zinc in the supernatant of mixed saliva and parotid saliva, copper in plasma, and protein in all fractions of saliva studied. Concentrations of zinc in salivary sediment and plasma did not vary with age. Age-related decreases (p less than 0.05) were found in concentrations of magnesium in mixed-saliva supernatant, copper in salivary sediment, and zinc and copper in hair. Males had higher concentrations of zinc in plasma (p less than 0.05) and of copper in sediment (p less than 0.01) than did females but lower amounts of copper in plasma and of protein in parotid saliva (p less than 0.05). Concentrations of zinc in saliva were not correlated with those in plasma or hair. Copper in mixed-saliva supernatant was positively associated with concentrations in plasma but negatively related to concentrations in hair. PMID- 2309654 TI - Validation of a new computerized technique for quantitating individual dietary intake: the Nutrition Evaluation Scale System (NESSy) vs the weighed food record. AB - A validation study was conducted in which food intake recorded by research volunteers using a new computerized technique, the Nutrition Evaluation Scale System (NESSy), was compared with food intake obtained from a weighed food record concurrently measured and recorded by metabolic unit dietary staff. Nine women between ages 23 and 35 y resided in the metabolic research unit and recorded their food intake with NESSy for 16 consecutive days. The mean of the differences between NESSy and the manual technique was not significant on a group basis (p less than 0.05) for food energy or any other nutrient. All mean differences were less than 5% and Pearson correlation coefficients ranged from 0.81 to 0.98 (p less than 0.0001), with all but iron, potassium, sodium, and preformed niacin having correlations greater than 0.92. For the majority of the individuals, accuracy within 10% of their actual dietary intake was found for energy and selected nutrients. NESSy is a new computerized approach to dietary intake assessment that yields accurate data on both a group and individual basis. PMID- 2309655 TI - Use of p-aminobenzoic acid to monitor compliance with prescribed dietary regimens during metabolic balance studies in man. AB - A new method is described for simultaneously monitoring compliance with prescribed-diet and urine-collection regimens during metabolic balance studies. It involves incorporation of the potassium salt of p-aminobenzoic acid (PABA) into provided foods and measurement of its extent of recovery in urine. A validation study was conducted in 10 healthy adults. During three consecutive 24 h periods, subjects consumed four foods per day that had each been supplemented with 72.0 mg PABA and also made complete urine collections. An additional 24-h urine collection was made by each subject for determination of baseline PABA excretion. The PABA was easily incorporated into the test foods and was not detected by taste. The recovery of the PABA in urine, determined by colorimetric assay, was 98.7 +/- 3.7% (means +/- SD) of intake. Thus, in metabolic studies for greater than or equal to 3 d, PABA can be used to provide a sensitive index of dietary compliance. PMID- 2309656 TI - Cow milk and insulin-dependent diabetes mellitus: is there a relationship? AB - Various cow-milk preparations have, with some variation, been reported to be diabetogenic in two animal models of insulin-dependent diabetes mellitus (IDDM), the BioBreeding (BB) rat and the nonobese diabetic (NOD) mouse. However, the suggestion of an inverse relationship between breast-feeding and IDDM based on epidemiological studies, remains controversial. There is a significant positive correlation between consumption of unfermented milk protein and incidence of IDDM in data from various countries. Conversely, a possible negative relationship is observed between breast-feeding at age 3 mo and IDDM risk. Diet may be an important permissive factor in the development of IDDM. PMID- 2309657 TI - Amino acid requirements in adult man. PMID- 2309658 TI - The effect of sodium chloride concentration, water content, and protein on the gas chromatographic headspace analysis of ethanol in plasma. AB - The authors used gas chromatographic headspace analysis to study the sodium chloride concentration dependence of the partitioning of acetonitrile, ethanol, n propanol, and t-butanol from water and plasma to headspace vapor. Increasing the sodium chloride concentration caused logarithmic increases in the partitioning. At 25 degrees C the slopes (log10[peak height]/mol sodium/L) obtained with the use of water or plasma were as follows: acetonitrile, 0.064 (0.059); ethanol, 0.126 (0.125); n-propanol, 0.152 (0.149); and t-butanol, 0.200 (0.183). Differences in water content between the two liquids may contribute to the small differences in the regression data. More importantly, saturation with sodium chloride at 25 degrees C produced solutions with different sodium molarities: 5.2 mol/L for water and 4.8 mol/L for plasma. This difference in salt concentration at saturation and the volatile dependent slopes can account for a large part of the error in plasma ethanol concentrations when measured with the use of aqueous external standardization and internal standardization with any of the other volatiles. Deproteinization of the plasma abolished the liquid phase-dependent differences in saturated salt concentration and partitioning. PMID- 2309659 TI - Histoplasmosis in patients with acquired immunodeficiency syndrome. Hematologic and bone marrow manifestations. AB - In areas where Histoplasma capsulatum infections are endemic in the United States, there is an increasing frequency of progressive disseminated histoplasmosis (PDH) as an opportunistic infection in patients with acquired immune deficiency syndrome (AIDS). The bone marrow and peripheral blood (PB) specimens in 13 patients with AIDS and PDH were reviewed. Anemia, leukopenia, and thrombocytopenia were found in 12, 10, and 7 patients, respectively. Circulating organisms were detected in the blood smears or buffy coat preparations from five patients and were associated with PB nRBCs and severe absolute monocytopenia. Morphologically, the marrow specimens showed one of four patterns: (1) no morphologic evidence of infection (two patients, one with a positive marrow culture); (2) discrete granulomas (two patients, both with positive marrow cultures); (3) lymphohistiocytic aggregates (six patients, four with positive marrow cultures); and (4) diffuse macrophage infiltrates (three patients, all with positive marrow cultures). Morphologic examination of the bone marrow combined with cultures is useful in diagnosing disseminated histoplasmosis in patients with AIDS. However, the morphologic findings in the bone marrow may be different in patients with AIDS compared with non-AIDS patients, and seemingly nondiagnostic morphologic features must be approached with a high degree of suspicion in diagnosing infections with H. capsulatum in this population. PMID- 2309660 TI - The effect of bacteremia on automated platelet measurements in neonates. AB - Platelet volume measurements have been used to differentiate consumptive and hypoplastic thrombocytopenia. Since thrombocytopenia is a frequent complication of neonatal sepsis, the authors explored the utility of correlating mean platelet volume (MVP) and platelet distribution width (PDW) with bacteremia. In a sample of 156 infants, there was a significantly increased presence of bacteremia in those infants with MPV greater than 10.8 fL and/or PDW greater than 19.1%. High MPV and PDW showed high specificity for detecting bacteremia (95% and 79%, respectively), and had good negative predictive value. Neonates with blood cultures positive at birth (early infection) tended to have normal platelet volumes, while those infected after three days of age (late infection) had dramatic increases in MPV and PDW. Changes in MPV and PDW should be noted when the diagnosis of late sepsis is considered. PMID- 2309661 TI - Measurement of platelet von Willebrand factor is dependent on method of platelet isolation. AB - The authors have compared platelet von Willebrand factor antigen and ristocetin cofactor activity measurements in a normal population, using two different previously published platelet isolation techniques. Preparation of a platelet lysate by platelet washes using Tyrode's albumin solution and inhibitors yielded a threefold higher vWF antigen and a twofold higher ristocetin cofactor activity measurement as compared to platelets isolated by tris buffered saline washes containing 0.1% (weight/volume) Na2EDTA. Contamination by plasma von Willebrand factor to account for the higher values found by the first method was excluded by monitoring the presence of added purified I125 von Willebrand factor to platelet rich plasma. vWF multimer analysis showed the same distribution of multimers in both preparations but suggested a relative decrease in lower molecular weight multimers with the second method. Platelet isolation can result in significant loss of platelet von Willebrand factor, with a preferential loss of lower molecular weight multimers, likely resulting from unintentional platelet release. PMID- 2309662 TI - Rapid differentiation of subarachnoid hemorrhage from traumatic lumbar puncture using the D-dimer assay. AB - The D-dimer assay of 40 cerebral spinal fluid (CSF) samples accurately differentiated subarachnoid hemorrhage (SAH) from traumatic lumbar puncture. The D-dimer assay was positive in all six patients with subarachnoid hemorrhage. Negative D-dimer values were obtained in control groups of 14 patients with hemorrhagic CSF secondary to traumatic lumbar puncture (LP) and in 20 patients with normal CSF. The D-dimer assay proved to be a better test than xanthochromia or the decline in erythrocyte count in sequentially collected tubes in differentiating subarachnoid hemorrhage from traumatic LP. PMID- 2309663 TI - Evaluation of the Behring Nephelometer for detection of low level urinary albumin. AB - Mildly increased urinary albumin excretion rates and concentrations, below the quantity normally detected by conventional urinary protein and albumin methods, have prognostic significance for the development of nephropathy in patients with diabetes mellitus. The authors evaluated the automated Behring Nephelometer using Behring reagents for the detection of low level urinary albumin. Within run coefficients of variation (CVs, N = 20) are 1.7%, 1.3%, and 2.4% at mean urinary albumin levels of 16, 70, and 217 mg/L, respectively. Between run CVs (N = 20) are 4.5%, 2.6%, and 4.4% at mean albumin levels of 19, 71, and 239 mg/L, respectively. The method is sensitive to 3 mg/L. Hemoglobin, immunoglobulins, bilirubin, urea, and radiographic contrast media beyond a few hours of injection show no significant interference at levels normally expected from clinical specimens. Analysis is unaffected by pH within the physiologic range. Most urine specimens are stable for at least eight days when refrigerated at 4 degrees C. Specimen centrifugation before analysis is essential to avoid a negative bias that occurs when analyzing uncentrifuged refrigerated samples. Preanalytical freezing produces results higher than those observed in fresh or refrigerated samples. The authors conclude that automated nephelometry using the Behring Nephelometer is a convenient, simple, and accurate technique for the determination of low level urinary albumin. PMID- 2309664 TI - Abstracts of paper and poster presentations, scientific sessions of the spring meeting of the American Society of Clinical Pathologists and the College of American Pathologists. March 24-29, San Francisco, California. PMID- 2309665 TI - An American Board of Orthodontics case report. AB - A case report is presented of a Class III, right subdivision malocclusion in the permanent dentition. There were significant arch form asymmetries, crossbite, crowding, and a midline discrepancy. The case was treated to the standards of the American Board of Orthodontics. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirements for the certification process conducted by the Board.] PMID- 2309666 TI - Facial growth in males 16 to 20 years of age. AB - Postpubertal craniofacial skeletal and dental changes were examined from lateral cephalograms taken when subjects were 16, 18, and 20 years of age. The sample consisted of males with no previous orthodontic treatment who had Class I skeletal and dental characteristics. Mandibular growth was found to be statistically significant for the age periods of 16 to 18 years and 18 to 20 years. Growth from 16 to 18 years was greater than that from 18 to 20 years. Maxillary and mandibular growth were highly correlated at each age period. However, overall mandibular growth was approximately twice that of overall maxillary growth. Mandibular growth was found to involve an upward and forward rotation, a result of posterior vertical growth exceeding anterior vertical growth. Lower incisors were found to tip lingually with increasing age. Incremental changes in mandibular cephalometric measurements were found to be equivalent when measured from either articulare or condylion, indicating the interchangeability of the landmarks for growth estimates. PMID- 2309667 TI - External nasal morphology and respiratory function. AB - Clinicians have been known to characterize nasal respiratory function on the basis of subjective appraisal of external facial morphology. Certain nasal morphologic features have been assumed to be associated with impaired nasal function. The purpose of this study was to develop measures of anterior external nasal morphology and to determine whether any of these measures correlate with nasal function. Nasal casts were produced from impressions of 60 postpubertal white subjects from which four measures were made to characterize nasal morphology: (1) nasal base shape, (2) minimum nasal orifice width, (3) nasal orifice shape, and (4) nasal orifice area. Nasal function was evaluated by measuring nasal airway resistance by means of posterior rhinomanometry and by measuring the air respired nasally and orally by means of the simultaneous nasal and oral respirometric technique. No significant correlations were found between external nasal morphology and nasorespiratory function. These findings underscore the necessity of avoiding assumptions about breathing function on the basis of clinical appraisal of external nasal form. PMID- 2309668 TI - Effects of orthodontic bands on microbiologic and clinical parameters. AB - The aim of this study was to evaluate the effect of placement of orthodontic bands on the gingival tissues and the microbial composition of dental plaque. Ten subjects undergoing orthodontic treatment completed the study. In each subject four sites were examined: two test sites with orthodontic bands and two control sites free of bands. Clinical and bacterial examinations were performed before the beginning of the treatment and 5, 7, 47, 72, and 90 days after placement of the orthodontic appliances. Plaque index (Pl I) and bleeding scores increased significantly on banded teeth as compared with control sites. Probing depth remained within normal values for both test and control groups. The composition of dental plaque determined by dark-field microscopy showed significant shifts in the test sites after banding. Changes consisted of an increase in the percentage of spirochetes, motile rods, filaments, and fusiforms; conversely, a decrease in cocci was noted. During the same period no significant changes in the bacterial distribution were observed in the control group. PMID- 2309669 TI - The influence of the SPEED bracket's self-ligating design on force levels in tooth movement: a comparative in vitro study. AB - In the SPEED bracket system the arch wire is retained in the arch wire slot by means of a built-in, escape-proof, flexible spring clip. Unlike the traditional edgewise bracket, it requires no ligature tie, thus ostensibly reducing the frictional force generated by the more-established elastomeric or steel-tie ligature systems. An in vitro study was designed to compare the level of force required to move four distinct arch wires a similar distance, on six occasions, through four ligated bracket systems and the self-ligated SPEED bracket. The results consistently demonstrated a significant decrease in the force level required for the SPEED bracket with all four arch wires when compared with elastomeric and steel-tie ligation in both metal and plastic bracket systems. PMID- 2309670 TI - The malpractice morass and practice activities of orthodontists. AB - This study examined the association between malpractice, measured by perception and experience scores, and practice activities of orthodontists. Data from 184 Florida orthodontists were obtained in the form of continuous/ordinal responses to survey questions in five areas: demographic, work load, personality, perception of the malpractice environment, and practice activities (malpractice experience, record taking, disclosure, and rapport). Mutually exclusive recency categories were selected on the basis of when an activity was last performed. Descriptive statistics and plots of the data were examined. A malpractice experience score for each respondent was determined by means of factor analysis procedures on the activity question responses. The association between perception/experience scores and responses to activity, demographic, work load, and personality questions were examined with the use of stepwise multiple regression procedures. The results indicated that practice activities, in the areas of record taking and doctor-patient rapport, were moderately associated with both experience scores (R2 = 0.47, p = 0.08) and perception scores (R2 = 0.29, p less than 0.06). Perception of the malpractice environment was associated with practice activities of orthodontists but to a lesser extent than active experiences in that environment were. PMID- 2309671 TI - Legal aspects of orthodontic practice: risk management concepts. Second opinions. PMID- 2309672 TI - Educational malpractice: a look in the mirror. PMID- 2309673 TI - Reply to Ahlin's comments in August issue. PMID- 2309674 TI - Computer analysis of wire function: clarification. PMID- 2309675 TI - Meeting of the Food and Drug Administration Gastroenterology-Urology Device Section Advisory Panel on Extracorporeal Shock-Wave Lithotripsy for Gallbladder Stones. October 19, 1989. PMID- 2309676 TI - On-demand treatment for duodenal ulcers: has its time come? PMID- 2309677 TI - Rapid insorption of small particles in the gut. AB - Little is known about the uptake of small particles by the epithelium of the gastrointestinal tract. In our study, we investigated the absorption and transport of synthetic and natural particles by means of scanning electron microscopy (SEM). In Wistar rats, closed loops of jejunum with intact mesenteric blood supply were established in ether anesthesia so that we might study the absorption of latex particles of different sizes. After variable absorption times, loops were removed and prepared for examination by microscopic techniques. The average surface of M-cells was 35 +/- 2 microns2, whereas the total number was dependent on follicle size. The proportion of M-cells to absorptive-like enterocytes on follicle epithelium was 1:12. Latex particles were found easily on the surface of M-cells, and for the most part they were surrounded by microfolds. In only 10 min from the time of application, latex beads were concentrated or even included within macrophages of the dome of lymph follicles. The results indicate that primary insorption of small particles occurs in M-cells of Peyer's patches, and time of insorption is dependent on particle size. PMID- 2309678 TI - Results of a repeat television-advertised mass screening program for colorectal cancer using fecal occult blood tests. AB - The results of a 1987 television-advertised colorectal screening program using fecal occult blood tests (FOBT) are compared with the initial 1986 program (results in parentheses). In the 1987 program, 73,508 fecal occult blood test (FOBT) kits were distributed free of charge, of which 63% were returned for analysis (57,000, 53%). Twenty-five percent of persons from the initial screening participated again in the 1987 program: 1,303 or 2.8% of persons had a positive screen (1,165, 3.9%). The predictive value of a positive screen was 23% for an adenomatous polyp and 8% for colorectal cancer (22%, 8%). Seventy-nine percent of the cancers detected were Dukes A or B or carcinoma in situ (78%). In order to promote a more thorough diagnostic work-up in positive screenes, a suggested diagnostic algorithm for the work-up of a positive FOBT was sent to participating physicians. Despite this, 35% of positive screenees had a diagnostic work-up limited to a repeat FOBT, and/or sigmoidoscopy only (32%). In conclusion, television-advertised mass screening programs consistently enroll large numbers of participants. The rate of compliance (percent of kits returned) and the limited diagnostic evaluation of persons with a positive screen appear to be the major factors limiting the success of our screening program. PMID- 2309679 TI - Impairment of autonomic reflexes in cirrhosis. AB - Autonomic dysfunction may contribute to the hemodynamic disturbances in cirrhosis. Tests of autonomic function were performed in 20 patients with cirrhosis and 20 healthy subjects. The patients with severe cirrhosis (Child's grade B or C) had significant reductions in the Valsalva ratio, the heart rate variation during both facial immersion in water and deep breathing, the pressor response to forearm isometric exercise, and the heart rate response to dynamic exercise. The cold pressor test and the heart rate response to lying down were unaffected. These results indicate impairment of both sympathetic and parasympathetic reflexes in severe cirrhosis which may contribute to the hemodynamic disturbances of cirrhosis. Further studies are required to define the site of these defects. PMID- 2309680 TI - Bacterial esophagitis: an often forgotten cause of odynophagia. AB - Bacterial esophagitis is uncommon and has not been well characterized. We present a patient who fulfills the strict definition of bacterial esophagitis set forth by Walsh: "histopathologically demonstrable bacterial invasion of esophageal mucosa or deeper layers with no concomitant fungal, viral, or neoplastic involvement or previous surgery of the esophagus." Bacterial esophagitis should be considered in all immunocompromised patients presenting with odynophagia; however, its occurrence in association with human immunodeficiency virus infection has not yet been reported. Bacterial esophagitis can be a source of occult sepsis and requires different therapy than the other forms of infectious esophagitis. PMID- 2309681 TI - Familial multiple upper gastrointestinal leiomyoma. AB - This report describes three adult members of a family who developed leiomyomas in the muscularis propria of their upper gastrointestinal tract. When in their thirties, numerous leiomyomas were present in ileum and jejunum. In their sixties, multiple and confluent esophageal leiomyomas formed the clinical picture of esophageal leiomyomatosis. Presenting symptoms were esophageal obstruction and hemorrhage. This is the first case in the published literature describing an association of familial multiple upper gastrointestinal leiomyomas with esophageal leiomyomatosis. PMID- 2309682 TI - Multiple hepatic abscesses: cholangiographic changes simulating sclerosing cholangitis and resolution after percutaneous drainage. AB - A 59-yr-old man developed multiple hepatic abscesses following an episode of diverticulitis. A percutaneous transhepatic cholangiogram (PTC) showed changes typical of sclerosing cholangitis complicated by multiple hepatic abscesses. No biliary tract stones were seen either on ultrasound or PTC. A single drain left in the right biliary tree and a course of intravenous antibiotics resulted in complete normalization within 14 days of the previously involved biliary tree. PMID- 2309683 TI - Multiple actinomycotic abscesses of the liver. PMID- 2309684 TI - Gastrointestinal bleeding in Crohn's disease: the role of acquired factor deficiency. PMID- 2309685 TI - Gastrointestinal symptoms in diabetic patients: association or lack of association with neuropathy? PMID- 2309686 TI - Esophageal cancer mimicking squamous cell carcinoma of the lung: presentation with positive sputum cytology. PMID- 2309687 TI - Gastric bezoar complicating gastric stapling. PMID- 2309688 TI - Adenocarcinoma in hyperplastic polyp of the stomach. PMID- 2309689 TI - Successful treatment of refractory post-vagotomy syndrome with verapamil (Calan SR) PMID- 2309690 TI - Reasons for the removal of an enteric-coated slow-release potassium preparation from the market in France. PMID- 2309691 TI - 5-Aminosalicylic acid and its metabolite in breast milk during lactation. PMID- 2309692 TI - Reverse correlation between extent of colon involvement and number of affected joints in patients with ulcerative colitis and arthritis. PMID- 2309693 TI - Pericardial effusion during treatment with 5-aminosalicylic acid in a patient with Crohn's disease. PMID- 2309694 TI - Ileus as a complication of colonoscopy. PMID- 2309695 TI - Gallbladder papilloma causing right upper quadrant pain. PMID- 2309696 TI - The human genome project--some implications of extensive "reverse genetic" medicine. AB - Impressive progress has been made during the past several decades in understanding the pathogenesis of human genetic disease. The tools of molecular biology have allowed the isolation of many disease-related genes by forward and a few by reverse genetics, and the imminent completion of a complete human genetic linkage map will accelerate the genetic characterization of many more genetic diseases. The major impacts of the molecular characterization of human genetic diseases will be 1. To increase markedly the number of human diseases that we recognize to have major genetic components. We already understand that genetic diseases are not rare medical curiosities with negligible societal impact, but rather constitute a wide spectrum of both rare and extremely common diseases responsible for an immense amount of suffering in all human societies. The characterization of the human genome will lead to the identification of genetic factors in many more human diseases, even those that now seem too multifactorial or polygenic for ready understanding. 2. To allow the development of powerful new approaches to diagnosis, detection, screening and even therapy of these disorders aimed directly at the mutant genes rather than at the gene products. This should eventually allow much more accurate and specific management of human genetic disease and the genetic factors in many human maladies. The preparation of a fine structure physical map of the entire human genome together with an overlapping contiguous set of clones spanning entire chromosomes or large portions of chromosomes is rapidly becoming feasible, and the information that will flow from this effort promises eventually to affect the management of many important genetic diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309697 TI - Population genetic consequences of the fragile-X syndrome, based on the X inactivation imprinting model. AB - We have examined the population genetic consequences of the model of Laird (Genetics 117:587-599, 1987) in which the fragile-X syndrome is caused by "imprinting" of a mutant chromosome. The imprinting event in this model results from a block to reactivation of an inactive X chromosome prior to oogenesis. If it is assumed that males carrying the imprinted chromosome never reproduce, the frequencies of females and males carrying the imprinted chromosome are expected to be equal. When a mutation-selection balance is established, there are expected to be somewhat more than twice as many females carrying the nonimprinted fragile X as carry the imprinted fragile-X chromosome, the excess depending on the fertility of fragile-X females. Nonpenetrant (transmitting) males, i.e., those with the nonimprinted fragile-X chromosome, are expected to be present at about the same frequency as are males with the syndrome. More than one-third of the nonimprinted chromosomes in the population are expected to be newly arisen in each generation. We have considered possible alternatives to the model of a mutation-selection balance. Nonimprinted carrier females would need to have 100% fertility excess to avoid postulating a high mutation rate to account for the very high prevalence of the syndrome. PMID- 2309698 TI - The red-green visual pigment gene region in adrenoleukodystrophy. AB - Although recent data established that a specific very-long-chain fatty acyl-CoA synthetase is defective in X-linked adrenoleukodystrophy (ALD), the ALD gene is still unidentified. The ALD locus has been mapped to Xq28, like the red and green color pigment genes. Abnormal color vision has been observed in 12 of 27 patients with adrenomyeloneuropathy (AMN), a milder form of ALD. Furthermore, rearrangements of the color vision gene cluster were found in four of eight ALD kindreds. This led us to propose that a single DNA rearrangement could underlie both ALD and abnormal color vision in these patients. Study of 34 French ALD patients failed to reveal a higher than expected frequency of green/red visual pigment rearrangements 3' to the red/green color vision gene complex. The previous report of such rearrangements was based on small numbers and lack of knowledge that the frequency of "abnormal" color vision arrays on molecular analysis was twice as high as expected on the basis of the frequency of phenotypic color vision defects. The red/green color pigment (R/GCP) region was studied by pulsed-field gel electrophoresis in 14 of these patients, and we did not find any fragment size difference between the patients and normal individuals who have the same number of pigment genes. The R/GCP region was also analyzed in 29 French and seven North American ALD patients by using six genomic DNA probes, isolated from a cosmid walk, that flank the color vision genes. No deletions were found with probes that lie 3' of the green pigment genes. One of the eight previously reported ALD individuals has a long deletion 5' of the red pigment gene, a deletion causing blue cone monochromacy. This finding and the previous findings of a 45% frequency of phenotypic color vision defects in patients with AMN may suggest that the ALD/AMN gene lies 5' to the red pigment gene and that the frequent phenotypic color vision anomalies owe their origin to deleted DNA that includes regulatory genes for color vision. It is possible, however, that phenotypic color vision anomalies in AMN may be phenocopies secondary to retinal or neural involvement by the disease. The single case of blue cone monochromacy may therefore be a fortuitous coincidence of two diseases. PMID- 2309699 TI - Evaluation of birth defect histories obtained through maternal interviews. AB - Etiologic studies of birth defects often use family history information provided by parents of patients. The validity of this information has not been adequately assessed. Using data from the Atlanta Birth Defects Case-Control study, we evaluated sensitivity, specificity, and positive predictive value of mothers' responses regarding the presence of birth defects in their offspring. A total of 4929 mothers of infants with major structural defects ascertained by the Metropolitan Atlanta Congenital Defects Program and a total of 3,029 mothers of normal infants were asked whether their babies had had a birth defect or a health problem diagnosed during the first year of life. Interviewers and coders of maternal responses were blinded to the case-control status of infants. Sensitivity (the proportion of case mothers who gave responses that could be coded as denoting a major birth defect) was 61%. Specificity (the proportion of control mothers who gave responses that could not be coded as denoting a major birth defect) was 98%. The positive predictive value (the proportion of mothers who gave a major-birth-defect response who in fact had babies with major birth defects) was estimated as 47%. Sensitivity, specificity, and positive predictive value varied by maternal sociodemographic factors such as race and education, as well as by type of defect. These results suggest that family history data obtained through maternal interviews should be cautiously interpreted and, if not properly validated, may alter estimates of recurrence risks. PMID- 2309700 TI - Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq. AB - Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogenesis. As a first step in identifying genes involved in human development, we used a candidate-gene-and-region approach to look for a linkage to VWS. Six families with 3 or more generations of affected individuals were studied. Evidence for linkage (theta = 0.02, lod score = 9.09) was found between the renin (REN) gene on 1q and VWS. Other linked loci included CR1, D1S58, and D1S53. The genes for laminin B2 (LAMB2), a basement-membrane protein, and for decay-accelerating factor (DAF) were studied as possible candidate genes on 1q. Recombinants between VWS and both LAMB2 and DAF excluded these genes from a causal role in the etiology of VWS for the families studied in this report. Multipoint linkage analysis indicated that the VWS locus was flanked by REN and D1S65 at a lod score of 10.83. This tight linkage with renin and other nearby loci provides a first step in identifying the molecular abnormality underlying this disturbance of human development. PMID- 2309701 TI - A long-range restriction map of the human chromosome 19q13 region: close physical linkage between CKMM and the ERCC1 and ERCC2 genes. AB - We report on the physical ordering of genes in a relatively small area of chromosome 19, segment q13, containing the locus for myotonic dystrophy (DM), the most frequent heritable muscular dystrophy of adulthood in man. DNAs from somatic cell hybrids with der 19q products that carry a breakpoint across the muscle specific creatine kinase (CKMM) gene were analyzed by Southern blotting using probes for CKMM, APOC2, and the repair genes ERCC1 and ERCC2. Results were combined with data from CHEF and field inversion-gel-electrophoresis separation of large-sized DNA restriction fragments to establish a map localizing both DNA repair genes and the CKMM gene within the same 250 kb of DNA, the order being cen CKMM-ERCC2-ERCC1-ter, with APOC2 being at more than 260 kb proximal to CKMM. Transcriptional start sites of the CKMM and DNA-repair genes are all on the telomeric side of the genes. Our results provide a framework for the construction of a larger physical map of the area, which will facilitate the search for the DM gene. PMID- 2309703 TI - Segregation analysis of idiopathic torsion dystonia in Ashkenazi Jews suggests autosomal dominant inheritance. AB - The results of segregation analysis applied to a family study of idiopathic torsion dystonia in Ashkenazi Jews are reported. The study is based on 43 probands (with age at onset prior to 27 years) from 42 nuclear families; pedigrees were extended systematically through all available first- and second degree relatives, who were directly examined and videotaped. Final diagnoses were based on exam information and blinded videotape review. Segregation analysis demonstrated that the data are consistent with autosomal dominant inheritance with 30% penetrance. Recessive and polygenic inheritance were strongly rejected. There was no evidence for sporadic cases or new mutations. The high incidence and dominant inheritance of early-onset idiopathic torsion dystonia in Ashkenazi Jews suggests genetic homogeneity within this population, making it especially useful for linkage studies of this disorder. PMID- 2309702 TI - Genotype assignment in Gaucher disease by selective amplification of the active glucocerebrosidase gene. AB - Genomic DNA prepared from human cells in culture was amplified by the polymerase chain-reaction technique using two primers specific for the active human glucocerebrosidase gene. The 1,036-bp amplified fragment derived from the active gene was tested for the existence of three mutations--designated "370," "NciI," and "HhaI"--by allele-specific oligonucleotide hybridization. The results obtained from the cell lines examined permitted a clear distinction between homozygous affected, heterozygous, and normal genotypes. However, 28% of the possible affected loci were normal with respect to the three mutations, indicating the presence of additional mutations that remain to be elucidated. While the NciI mutation could be found in both Ashkenazi Jewish and non-Jewish type 1 patients, the only homozygotes with this mutation had the neurological (type 2 or type 3) form of the disease. The 370 mutation, on the other hand, was only present in type 1 patients and was not identified among any of the patients with neurologic forms of the disease. PMID- 2309704 TI - Determination of Y chromosome aneuploidy in human sperm nuclei by nonradioactive in situ hybridization. AB - Sperm nuclei from eight normal, healthy donors were hybridized in situ with the biotin-labeled Y-specific pHY2.1 DNA probe to evaluate the X:Y ratio, the location of the Y chromosome, and the frequency of Y aneuploidy in human sperm. The streptavidine-horseradish-peroxidase and DAB detection system used permitted the unequivocal identification of sperm heads with zero, one, or two hybridization signals and proved superior to either quinacrine staining or radioactive in situ hybridization. The low incidence of 0.27% of sperm nuclei with two Y chromosomes that was found is similar to the frequency of XYY males among newborns. The average proportions of X- and Y-bearing sperm nuclei were 50.3% and 49.4%, respectively, corresponding to the expected 1:1 ratio. The Y heterochromatin was located in the central part of the nucleus in 58% of the Y carrying sperm cells. PMID- 2309705 TI - A genetic study of Hirschsprung disease. AB - Hirschsprung disease, or congenital aganglionic megacolon, is commonly assumed to be a sex-modified multifactorial trait. To test this hypothesis, complex segregation analysis was performed on data on 487 probands and their families. Demographic information on probands and the recurrence risk to relatives of probands are presented. An increased sex ratio (3.9 male:female) and an elevated risk to sibs (4%), as compared with the population incidence (0.02%), are observed, with the sex ratio decreasing and the recurrence risk to sibs increasing as the aganglionosis becomes more extensive. Down syndrome was found at an increased frequency among affected individuals but not among their unaffected sibs, and the increase was not associated with maternal age. Complex segregation analysis was performed on these family data. The families were classified into separate categories by extent of aganglionosis. For cases with aganglionosis beyond the sigmoid colon, the mode of inheritance is compatible with a dominant gene with incomplete penetrance, while for cases with aganglionosis extending no farther than the sigmoid colon, the inheritance pattern is equally likely to be either multifactorial or due to a recessive gene with very low penetrance. A model of gene action with random effects during morphogenesis is compatible with our observations. PMID- 2309706 TI - Selecting pedigrees for linkage analysis of a quantitative trait: the expected number of informative meioses. AB - With evidence of segregation at a major locus for a quantitative trait having been found, a logical next step is to select a subset of the pedigrees to include in a linkage study to map the major locus. Ideally this subset should include much of the linkage information in the sample but include only a fraction of the pedigrees. We previously described a strategy for selecting pedigrees for linkage analysis of a quantitative trait on the basis of a pedigree likelihood-ratio statistic. For quantitative traits controlled by a major locus with a rare dominant allele, the likelihood-ratio strategy extracted nearly all the information for linkage while typically requiring marker data on only about one third of the pedigrees. Here, we describe a new strategy to select pedigrees for linkage analysis on the basis of the expected number of potentially informative meioses in each pedigree. We demonstrate that this informative-meioses strategy provides an efficient and more general means to select pedigrees for a linkage study of a quantitative trait. PMID- 2309707 TI - Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1). AB - We have determined that two infants with perinatal lethal osteogenesis imperfecta in one family had the same new dominant point mutation. Although not detected in his dermal fibroblast DNA, the mutation was detected in somatic DNA from the father's hair root bulbs and lymphocytes. The mutation was also detected in the father's sperm, demonstrating that mosaicism in the father's germ line explains recurrence. The presence of both germ-line and somatic mosaicism indicates that the mutation occurred prior to segregation of the germ-line and somatic cell progenitors. About one in eight sperm carry the mutation, which implies that at least four progenitor cells populate the germ line in human males. The observation that the mosaic individual is clinically normal suggests that genetic diseases can have both qualitative and quantitative components. PMID- 2309708 TI - Molecular analysis of the gene of the alpha 1-antitrypsin deficiency variant, Mnichinan. AB - Mnichinan, a variant of alpha 1-antitrypsin (alpha 1-AT) was detected in a Japanese individual with serum alpha 1-AT deficiency (18 mg/dl), associated with aggregated alpha 1-AT molecules in the hepatocytes. Cloning and sequencing of the 10,627-bp-long region containing the Mnichinan gene and the normal M1(Val213) alpha 1-AT gene revealed all five exons of the Mnichinan gene to be identical with the M1(Val213) alpha 1-AT gene, except for two changes: a TTC trinucleotide deletion in the codon for amino acid Phe52 and a G-A substitution, by which the normal Gly148 (GGG) became Arg148 (AGG). Dot blot analysis of the polymerase chain-reaction-amplified DNA derived from the proband and other family members showed both mutations to be associated with an alpha 1-AT deficiency phenotype. Ninety-eight alpha 1-AT alleles were all negative for both changes. Comparison of the region, except for five exons between the Mnichinan and M1(Val213) genes, demonstrated one base difference in the 5' flanking region and 14 base changes in the introns. All exon-intron junctions were identical, and base changes in the 5' flanking region did not seem significant. The G-A substitution in codon 148 of the Mnichinan gene could not be responsible for the alpha 1-AT deficiency phenotype because Arg- and not Gly- was located at the corresponding position of the protein C inhibitor belonging to the serine protease inhibitor superfamily. The deletion of Phe52 may cause the newly synthesized alpha 1-AT protein to aggregate, resulting in alpha 1-AT deficiency. Comparison of the alpha 1-AT gene sequences available indicated that the C-T substitution at the CpG dinucleotide has an important role in generation of variants and nucleotide changes in the noncoding regions of the alpha 1-AT gene. PMID- 2309709 TI - Individual identification by DNA analysis: points to consider. Ad Hoc Committee on individual identification by DNA analysis, The American Society of Human Genetics. PMID- 2309710 TI - Lymphoblastoid cell lines from frozen whole blood: a quick and economical safeguard for linkage analysis. PMID- 2309712 TI - Collaborative approach to external consulting. PMID- 2309711 TI - Identifying sources of i.v. product waste. PMID- 2309713 TI - How much caffeine is too much in athletes? PMID- 2309714 TI - Coding and searching for adverse drug reactions. PMID- 2309715 TI - Pharmacy practice leadership in the 1990s. PMID- 2309716 TI - Prescriptions for ambulatory patients. PMID- 2309717 TI - Turbulence and tranquility in the new decade: pharmacy leader--managers in patient care. AB - Management challenges that face pharmacy in the 1990s are described. Tichy's rope metaphor--intertwined cultural, technical, and political strands of an organization--is applied to problems faced by pharmacy managers; effective managers keep the organization strong by preventing the strands from working at cross-purposes to unravel the rope. Pharmacy's culture--its shared beliefs and values--is changing as "altruistic" institutional pharmacists form home care businesses, pharmacists identify more strongly with the profession than with their institutions, clinical pharmacists identify more strongly with the medical team, and cost control becomes more important. Institutional pharmacy must identify its desired outcomes and apply technology to achieve them. The patient's bedside is the best place for pharmacists to influence prescribing and monitor drug therapy; technology could be used to process patient information at the bedside and to dispense medications there. Current unit dose distribution systems isolate the functions of physician, pharmacist, and nurse, which must be integrated to make the system efficient and responsive. Standardized doses and dosage forms could be developed that are consistent with patient-care protocols; use of protocols allows the effectiveness of treatment methods to be evaluated and eliminates unnecessary therapy. Pharmacy can further its patient-care goals through political success with the medical staff; a pharmacy practice plan developed for a specific clinical area and presented to the medical staff is an example. Collaboration of pharmacists and physicians in a unified institutional strategy for drug use helps ensure appropriate decisions about therapy and prevents manufacturers from attempting to isolate an institution's pharmacists from its medical staff.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309718 TI - Empowering pharmacy through a collective vision. PMID- 2309719 TI - Three challenges: redefining production, embracing pharmaceutical care, and empowering staff. PMID- 2309720 TI - Our mission and our message: "safe use of drugs". PMID- 2309721 TI - Therapeutic risk-assessment model for identifying patients with adverse drug reactions. AB - The association between factors that place patients at risk for adverse drug reactions (ADRs) and the occurrence of ADRs was examined, and a therapeutic risk assessment model was developed. Theoretical risk factors for ADRs to digoxin and theophylline were identified through the literature by researchers at a private tertiary-care hospital. Data were then collected from two groups of 67 patient charts each during a 15-month period. One group of charts represented patients who had experienced an ADR to digoxin or theophylline. The other group represented matched control patients who had not experienced an ADR to either drug. ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modifications) ADR codes were assigned by medical records department personnel, and the ADRs were verified by using the Naranjo algorithm. Seven risk factors for each drug were found to be significantly associated with ADRs. A serum digoxin concentration greater than 2.5 ng/mL and elevated blood urea nitrogen were the two best predictors of an ADR to digoxin. The probability of experiencing an ADR to digoxin was 94.1% for a patient with both of these risk factors. A serum theophylline concentration greater than 25 micrograms/mL was the greatest predictor of an ADR to theophylline; the probability of experiencing an ADR to theophylline was 85.2% if a patient had that risk factor. The sensitivity and specificity of the therapeutic risk-assessment model were 92.9% and 61.8%, respectively, for digoxin and 95.8% and 84.0%, respectively, for theophylline. Several laboratory-based screening criteria demonstrated an ability to predict ADRs to digoxin and theophylline. PMID- 2309722 TI - Therapeutic outcome of elderly and nonelderly patients receiving home intravenous antimicrobial therapy. AB - The therapeutic outcomes of elderly patients receiving home i.v. antimicrobial therapy were compared with those of younger patients receiving the same therapy. Using predetermined inclusion and exclusion criteria, 150 consecutively referred patients were accepted into the study. These patients were receiving home i.v. antimicrobial therapy from three home-health-care pharmacies (HHCPs). Referred patients were classified as elderly (greater than or equal to 62 years old) or nonelderly. Data for these patients were compiled retrospectively using interviews and chart reviews. Outcome of the i.v. antimicrobial therapy was rated as either adequate or inadequate based on predetermined criteria. Outcomes were analyzed for each HHCP and for the pooled data. The mean age of the pooled nonelderly group was 38 +/- 14 years, and the mean age of the pooled elderly group was 71 +/- 6 years. Adequate outcomes were noted in 70% of the pooled samples of elderly patients and 76% of the pooled samples of nonelderly patients. The difference between the outcomes of patients in the two age groups was not significant. In this carefully selected population, elderly and nonelderly patients receiving home i.v. antimicrobial therapy had similar therapeutic outcomes. PMID- 2309723 TI - Comprehensive pharmaceutical services in the outpatient surgery center of a health maintenance organization. AB - The pharmaceutical services provided to the outpatient surgery center of a health maintenance organization (HMO) are described. The satellite pharmacy is managed by the nearby central pharmacy. The satellite pharmacist prepares and dispenses all needed medications and i.v. admixtures, maintains the inventory of all drugs and i.v. supplies, and supplies clinical and drug information. The pharmacist ensures that i.v. admixtures are made according to guidelines, that drug interactions and drug allergies are guarded against, and that each patient has access to oral pain medications and medication counseling while still in the recovery room. The tighter inventory control created by this arrangement helps to reduce costs, and the surgical nursing staff has been relieved of many medication related activities. The presence of the pharmacist in the surgery center also allows for more accurate documentation of controlled-drug dispensing. The presence of a pharmacist in the surgery center has ensured strict control of drug use and enabled nurses to spend more time on direct patient care. PMID- 2309724 TI - Outpatient pharmacy redesign to improve work flow, waiting time, and patient satisfaction. AB - An outpatient pharmacy redesign in which a pharmacist located outside the dispensing area speaks with each patient before the prescription is processed is described, and the effect of patients' waiting time and satisfaction is reported. Adoption of an open pharmacy plan at a Veterans Administration outpatient pharmacy allows patients to present their prescriptions to pharmacists in consultation booths equipped with computer terminals. The pharmacist promptly identifies and resolves any problem associated with a prescription or medication profile. The prescription then enters the dispensing work area, which was also redesigned to improve efficiency; patients now pick up their medications at a window on the opposite end of the dispensing area from where the pharmacist initially receives the prescription. Workload data and waiting times before and after implementation of the open pharmacy showed that prescriptions could be processed more quickly under the new system; average waiting times decreased from more than one hour to 30 minutes. Interviews of randomly selected patients indicated that the reduced waiting times led to increased patient satisfaction. The open pharmacy design appeared to improve work flow and to improve patient satisfaction by decreasing waiting times. PMID- 2309725 TI - Pharmacist involvement in a thyroid clinic. AB - The patient-care activities of a pharmacist in a thyroid clinic are described. Since 1978 a pharmacist has been an active member of the staff of a thyroid clinic associated with a 500-bed university hospital. More than 1500 patients are referred to the clinic each year. The pharmacist initiates, maintains, or modifies the drug therapy of selected patients with physician-diagnosed thyroid disorders under the guidance of written protocols approved by the chief endocrinologist. Most patients treated by the pharmacist are receiving thyroid suppression therapy, antithyroid drugs for Graves' disease, or thyroid hormone supplementation after surgery or after radioactive iodine therapy. The pharmacist assesses patients, prescribes medications, orders laboratory tests, charts visits and therapeutic plans, and educates patients about their conditions. Major changes in thyroid status and drug therapy are always discussed with the chief endocrinologist. The pharmacist also participates in educational programs to influence prescribing by physicians, provides drug information, serves as a preceptor to pharmacy students, and is investigating the equivalence of levothyroxine preparations in vivo and in vitro. An audit of patient outcomes showed that the pharmacist is highly effective in her role as a giver of direct patient care. A pharmacist's role in a thyroid clinic can consist of clinical practice, education, preceptorship, and research. PMID- 2309726 TI - Computerized ambulatory-care pharmacy information system for direct order entry by prescribers. AB - A computer system that links prescribers in a diabetes center to an ambulatory care satellite pharmacy is described. In 1988 an ambulatory-care center serving the diabetic patients of a 437-bed university teaching hospital moved to a new location. To maintain efficient communication of prescription information from the diabetes center to a designated ambulatory-care satellite pharmacy, a program that enables diabetes center prescribers to enter their orders directly into the satellite pharmacy computer system was implemented. The pharmacy department's prescription-entry screen was reprogrammed so that it could be more easily used by prescribers, and a "default" list of the most frequently prescribed drugs was generated to simplify direct order entry. Prescription information entered at the diabetes center is transmitted to the satellite pharmacy; the filled prescriptions are usually ready by the time patients arrive. The average number of prescriptions entered into the computer per week remained steady during the first 14 weeks that the system was in use but increased substantially after diabetes center personnel were given a summary of use data and other information pertaining to the new system. However, because of the availability of only one terminal for order entry and the inherent ease and speed of writing prescriptions on paper, use of the system has not met expectations despite the benefits it offers. Prescribers in a diabetes center did not frequently enter prescription information into a computer system linked to the hospital's ambulatory-care pharmacy because the traditional method of writing prescriptions remained available and convenient. PMID- 2309727 TI - Hospital pharmacy-based service for patient-controlled analgesia. AB - A hospital pharmacy-based patient-controlled analgesia (PCA) service is described. The pharmacy department at a 255-bed community hospital instituted a comprehensive PCA service in 1985. Pharmacists were given thorough training in the clinical aspects of pain management and were taught how to use the PCA device; nurses also received instruction. An order for PCA is issued by a physician, who may then delegate decisions about medication choice, duration of therapy, and device settings to a clinical pharmacist. The pharmacist reviews the order and evaluates the patient's status. If PCA is appropriate, the pharmacist selects the analgesic agent and PCA device settings and prepares a pharmacy monitoring card. Orders for syringes are filled in the central pharmacy or by the decentralized pharmacist. Each order is entered into the i.v. drug profile and the i.v. drug computer file, and a narcotics control card is completed. The nurse programs the device, instructs the patient, and records the patient's level of pain control on a PCA-monitoring record. The pharmacist observes patients daily and records observations and changes on the pharmacy monitoring card. Use of the PCA service has grown from an average of 56 patient days per month in 1985 to 919 in 1989, and pharmacy department revenue has increased accordingly. A moderate increase in workload has been absorbed without the need for an increase in staff. Surveys show broad acceptance of the service by physicians, nurses, and patients. A hospital pharmacy-based PCA service offered patients better control of pain, allowed pharmacists to demonstrate competence in non-distributive functions, increased the visibility of the pharmacy department, and was a source of revenue. PMID- 2309728 TI - Sorption of various drugs in polyvinyl chloride, glass, and polyethylene-lined infusion containers. AB - The sorption of chloroquine sulfate, diazepam, isosorbide dinitrate, lorazepam, midazolam, nitroglycerin, promethazine hydrochloride, thiopental sodium, and warfarin sodium to three types of containers was studied. Appropriate amounts of the drugs were added to 500 mL of 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags, glass bottles, and Clear-Flex bags composed of a laminate of polyethylene, nylon, and polypropylene. The containers were stored in the dark at room temperature for 24 hours. Samples were taken at various intervals and assayed for drug concentration by high-performance liquid chromatography. There were no appreciable changes in pH after 24 hours, and all the admixtures remained clear and colorless. The potency of chloroquine sulfate, lorazepam, midazolam, promethazine hydrochloride, and thiopental sodium remained unchanged in glass, PVC, and Clear-Flex containers. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium did not show any sorption to glass bottles and Clear-Flex bags. In PVC bags, however, up to 55% of diazepam, 23% of isosorbide dinitrate, 51% of nitroglycerin, and 24% of warfarin sodium was lost during the 24-hour study period. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium in 0.9% sodium chloride injection showed a loss of potency when stored in PVC containers for 24 hours at room temperature, but none of the drugs studied lost potency when stored in glass bottles and Clear-Flex bags. PMID- 2309729 TI - Recovery of phenytoin suspension after in vitro administration through percutaneous endoscopic gastrostomy Pezzer catheters. AB - Various methods of administering phenytoin suspension through a percutaneous endoscopic gastrostomy (PEG) Pezzer catheter were evaluated in vitro to determine which method resulted in the most complete recovery of phenytoin. To determine the effect of temperature on phenytoin recovery, 12 mL of phenytoin suspension (Dilantin-125, 125 mg/5 mL) was administered through three separate 35.5-cm 20 French latex PEG Pezzer catheters under each of three temperature conditions (suspension 11.8 degrees C and catheter 22 degrees C, suspension and catheter 22 degrees C, and suspension 22 degrees C and catheter 37 degrees C). To determine the effect of the administration method, 12-mL aliquots of phenytoin suspension were injected into the catheter by seven methods that varied with respect to catheter temperature, dilution of suspension, and irrigation of catheter. Each method was tested in triplicate, and samples were assayed by high-performance liquid chromatography. Varying the temperature of the catheter or suspension had little effect on the recovery of phenytoin. There was no appreciable loss of phenytoin when the suspension was undiluted, regardless of whether the catheter was irrigated. The greatest losses were seen when the suspension was diluted before administration. Irrigation also caused a decrease in recovery, but to a lesser extent than dilution. Until the effects of administering multiple doses of phenytoin through PEG Pezzer catheters are investigated, phenytoin suspension should not be diluted before administration because of decreased recovery and increased administration time. PMID- 2309730 TI - Stability of heroin hydrochloride in infusion devices and containers for intravenous administration. AB - The stability of heroin hydrochloride in various drug-administration devices was studied. Heroin hydrochloride was supplied as the bulk powder by the National Institute on Drug Abuse and in the formulated dosage form by Evans Medical, Ltd. Stability was determined at concentrations of 1 and 20 mg/mL at room temperature (23-25 degrees C) and at 4 degrees C in a polyvinyl chloride (PVC) bag, a disposable glass syringe, and two disposable infusion devices. Studies at both concentrations also were conducted at 31 degrees C in the disposable infusion devices. All experiments were conducted in triplicate. A validated, stability indicating, high-performance liquid chromatography assay was used. Heroin hydrochloride remained stable for a minimum of 15 days in the PVC bag and the Infusor infusion device at the tested temperatures and concentrations. In the glass syringe, heroin hydrochloride was shown to be stable for a minimum of 15 days at both 1 mg/mL and 20 mg/mL if refrigerated at 4 degrees C, whereas at room temperature it was stable for a minimum of 7 days at 1 mg/mL and for 12 days at 20 mg/mL. In the Intermate 200 infusion device, heroin hydrochloride was stable for a minimum of 15 days at both concentrations and all temperatures except for the 1 mg/mL concentration at 31 degrees C. In the latter case, stability was for a minimum of two days. No substantial changes in physical appearance or pH were observed in any of the containers under the conditions studied. Heroin hydrochloride can be repackaged in the disposable glass syringe, PVC bag, and each of the disposable infusion devices for routine clinical use. PMID- 2309731 TI - Outcome-oriented approach to inspection of medication areas. PMID- 2309732 TI - Pharmacist monitoring of the timing of preoperative antibiotic administration. PMID- 2309733 TI - Potential effect of oral antimicrobial therapy on nurse staffing requirements. PMID- 2309734 TI - Physicians' attitudes toward drug-use evaluation interventions. PMID- 2309735 TI - Development and implementation of clinical pharmacokinetic services. AB - The basic issues involved in the development and implementation of pharmacokinetic dosing services are presented. A quality pharmacokinetic dosing service is activated by pharmacists immediately upon receipt of a consultation request or medication order. The patient's status is assessed, and recommendations are made for initial dosage, timing of blood sampling, and laboratory tests. Serum drug concentration data are interpreted and a maintenance dosage recommended. The patient is then monitored. The personnel selected for a dosing service need not have advanced pharmacy degrees but must be highly trainable. Their training should address basic pharmacokinetic concepts, the pharmacokinetics of specific drugs, and details on running the service and should be reinforced by extensive on-the-job training. As with other services, staffing should be tailored to workload. Continuous oral and written communication among the dosing service pharmacists and between the pharmacists and the medical and nursing staffs is essential to the smooth and expeditious operation of the service, as are complete and well-written policies and procedures. A quality dosing service cannot exist without commitment from hospital administration and the director of pharmacy and responsiveness of the nursing department and laboratory to the service's exacting requirements. Ongoing research is necessary to evaluate the pharmacokinetic models and software packages used and to find ways of conserving time. High-quality pharmacokinetic dosing services enhance patient care and the image of hospital pharmacy. PMID- 2309736 TI - Must a Catholic hospital inform a rape victim of the availability of the "morning after pill"? PMID- 2309737 TI - Salt-sensitive blood pressure and exaggerated vascular reactivity in the hypertension of diabetes mellitus. AB - PURPOSE: This study evaluates the effects of dietary salt restriction and loading on blood pressure in normotensive and hypertensive patients with non-insulin dependent diabetes mellitus (NIDDM). Salt sensitivity of blood pressure responses is compared to vascular reactivity to infused angiotensin II on the two sodium diets. PATIENTS AND METHODS: We studied 19 patients with NIDDM (seven normotensive, 12 hypertensive) and seven nondiabetic control subjects under metabolic balance after 6 days on a constant low- (20 mEq) sodium diet and again after 6 days on a high- (250 mEq) sodium diet. Salt sensitivity of blood pressure was determined by the increment in integrated 24-hour blood pressure values on changing from the low- to the high-sodium diet. Blood pressure and plasma aldosterone responses to a graded-dose infusion of angiotensin II were also examined on both sodium diets. RESULTS: Eight of 12 hypertensive patients with NIDDM displayed salt-sensitive blood pressure responses, whereas none of the normotensive patients with NIDDM or control subjects were salt-sensitive. Patients with NIDDM also had augmented blood pressure responses to infused angiotensin II on both sodium diets when compared to control subjects. Whereas controls had reduced vascular responses to angiotensin II on the low-sodium diet, these responses were not decreased in patients with NIDDM. Patients with NIDDM also retained more sodium on the high-sodium diet than did the control subjects. CONCLUSION: Hypertension in patients with NIDDM is frequently salt-sensitive, which may be due to sodium retention and enhanced vascular reactivity to angiotensin II. Since sodium restriction does not normally reduce vascular reactivity to angiotensin II in NIDDM, salt-restricted diets may be less effective in blood pressure control in hypertensive NIDDM. PMID- 2309738 TI - Coronary flow reserve, esophageal motility, and chest pain in patients with angiographically normal coronary arteries. AB - PURPOSE AND METHODS: To ascertain the relative prevalence of abnormalities of coronary flow reserve and esophageal function in patients with chest pain despite angiographically normal coronary arteries, 87 patients underwent invasive study of coronary flow reserve and, during the same week, esophageal testing. RESULTS: Sixty-three of the 87 patients (72%) demonstrated abnormalities of coronary flow reserve, as evidenced by an increase in coronary resistance during the stress of rapid atrial pacing after administration of ergonovine 0.15 mg intravenously (1.33 +/- 0.36 mm Hg.minute/mL), compared with pacing at the same heart rate before ergonovine administration (1.10 +/- 0.33 mm Hg.minute/mL). This higher coronary vascular resistance occurred in the absence of significant epicardial coronary artery luminal narrowing. Fifty-seven of these 63 patients (90%) with a coronary vasoconstrictor response to ergonovine described their typical chest pain during pacing stress, compared with only six of 24 patients (25%) who demonstrated no coronary flow abnormality (p less than 0.001). After administration of dipyridamole 0.5 to 0.75 mg/kg intravenously to 65 patients, the 48 patients with ergonovine-induced vasoconstriction had a significantly higher minimum coronary resistance, compared with the 17 patients without a coronary vasoconstrictor response to ergonovine (0.65 +/- 0.21 versus 0.47 +/- 0.13 mm Hg.minute/mL, p less than 0.03). Twenty of 87 patients (23%) had abnormal esophageal motility [nutcracker esophagus (11), nonspecific motility disorder (seven), and diffuse esophageal spasm (two)], including 16 of the 63 patients (25%) with abnormal coronary flow reserve. Twenty-four (28%) patients experienced their typical chest pain during motility testing, but only five of these patients met criteria for abnormal esophageal motility. Nine of 75 patients tested (12%) had their typical chest pain during Bernstein testing, and 18 of 38 patients (47%) tested had their typical chest pain provoked by intraesophageal balloon distention. CONCLUSIONS: Seventy-one of 87 patients (82%) with anginal-like chest pain and normal epicardial vessels in our series had a disorder of either coronary flow reserve, esophageal motility, and/or reproduction of typical chest pain during acid infusion. Of interest, chest pain was commonly encountered during cardiac and esophageal testing (85% of patients), regardless of the ability to demonstrate an abnormality of coronary flow reserve or abnormal esophageal function. This suggests that pain experienced by these patients may be a consequence of myocardial ischemia, esophageal dysfunction, abnormal visceral nociception, or a combination of any or all of these entities. PMID- 2309739 TI - Effects of diuresis on the characteristics of pleural fluid in patients with congestive heart failure. AB - PURPOSE: The pleural fluid that accumulates secondary to congestive heart failure is almost always a transudate based upon its level of protein and lactic acid dehydrogenase (LDH). Previous work has suggested that the characteristics of the fluid may change into those of an exudate with diuresis. The purpose of the present study was to determine whether aggressive diuresis does result in this change in pleural fluid characteristics. PATIENTS AND METHODS: Twelve patients with severe congestive heart failure (ejection fraction 23.9 +/- 9.6%) and pleural effusions were studied serially as they underwent diuresis. After an initial thoracentesis was performed, the patients then underwent aggressive diuresis for 12 to 48 hours with one or two follow-up thoracentesis. RESULTS: The mean weight loss during the study period was 4.5 +/- 2.8 kg. With diuresis the LDH level, LDH ratio, protein level, and protein ratio all increased significantly (p less than 0.05). All 12 patients had transudative pleural effusions at the onset of diuresis. However, despite the increases in the levels of protein and LDH with diuresis, only one patient's pleural fluid attained values compatible with an exudate. CONCLUSION: From this study we conclude that it is uncommon for a transudative pleural effusion due to congestive heart failure to develop the characteristics of an exudative pleural effusion with rapid diuresis. PMID- 2309740 TI - Skin necrosis associated with acquired protein C deficiency in patients with renal failure and calciphylaxis. AB - PURPOSE: To determine if the natural anticoagulant protein C plays a role in the pathogenesis of systemic calciphylaxis, a syndrome characterized by extensive vascular and soft tissue calcification and skin necrosis, which is similar to that seen in warfarin-induced skin necrosis. PATIENTS AND METHODS: The study population included five patients with end-stage renal disease and systemic calciphylaxis undergoing hemodialysis, 12 patients without evidence of calciphylaxis undergoing dialysis, eight patients with nephrotic syndrome, and eight normal healthy volunteers. Protein C antigen levels were measured by rocket immunoelectrophoresis, and functional activity was quantitated by a chromogenic assay and an anticoagulant assay utilizing the venom of Agkistrodon contortrix. RESULTS: Skin biopsy specimens of involved areas in three patients showed thrombotic occlusion of venules identical to that seen in warfarin-induced skin necrosis. Protein C antigen levels were normal in all groups. However, protein C activity was significantly reduced as measured by chromogenic (p less than 0.01) or anticoagulant assays (p less than 0.01) in patients with calciphylaxis compared with the other three groups. CONCLUSION: These findings suggest that hypercoagulability due to functional protein C deficiency may contribute to thrombosis, resulting in skin necrosis and digital gangrene in systemic calciphylaxis. PMID- 2309741 TI - Fatal nonthyroidal illness may impair nocturnal thyrotropin levels. AB - PURPOSE: This study was undertaken to assess whether circadian variation of thyrotropin (TSH) is affected by the severity of a nonthyroidal illness. PATIENTS AND METHODS: On the second day of admission to a medical intensive care unit, 20 consecutive patients with the major diagnosis of acute respiratory failure underwent TSH measurements at 8 A.M., 9 P.M., 11 P.M., and 1 A.M., with two sensitive assays. RESULTS: Six patients died, five of whom had hypothyroxinemia (thyroxine [T4] less than 5.5 micrograms/dL) (83%) on the day of the study, whereas only three of the 14 survivors had low T4 (21%; p less than 0.05). Baseline 8 A.M. TSH measured with the two assays was similar in both groups and there was a progressive increase in TSH in survivors and a decrease in nonsurvivors at 9 P.M. and 11 P.M. However, the difference at these time points was not statistically significant. At 1 A.M., TSH levels were significantly lower among nonsurvivors (0.75 +/- 0.34 microU/mL with assay 1, and 0.7 +/- 0.4 microU/mL with assay 2) than in survivors (2.3 +/- 0.46 microU/mL with assay 1, and 2 +/- 0.5 microU/mL with assay 2; p less than 0.005; Wilcoxon test). Five of the nonsurvivors and none of the survivors had a suppressed 1 A.M. TSH level (p less than 0.001), suggesting a good correlation between suppressed 1 A.M. TSH and mortality. After exclusion of patients receiving drugs known to affect TSH levels (two nonsurvivors and four survivors), the same dissociation in TSH changes was observed, and significantly lower 1 A.M. TSH levels were observed in nonsurvivors than in survivors (0.13 +/- 0.08 microU/mL versus 2.7 +/- 0.6 microU/mL with assay 1; p less than 0.01). Cortisol levels were significantly higher only at 8 A.M. in nonsurvivors whether patients receiving drugs were included in the analysis (41.6 +/- 3.2 versus 28.4 +/- 2.7 micrograms/dL; p less than 0.01) or not (45.3 +/- 4.6 versus 30.5 +/- 3.6 micrograms/dL; p less than 0.01). At other times, cortisol levels were similar in both groups. The 24-hour TSH areas under the curve were also lower in nonsurvivors than in survivors whether patients receiving drugs known to affect TSH levels were included or not. However, cortisol areas under the curve were similar in both groups. CONCLUSION: It is concluded that fatal illness is associated with a suppression of the late night TSH surge. PMID- 2309742 TI - Career development in academic medicine. AB - Clinical academic medicine desperately needs the continued infusion of talented young academicians, but many young faculty are not pursuing strategies that optimize their chances for academic survival. Many junior faculty are overburdened with clinical demands and do not have a well-focused research agenda. Such situations will hinder the full development of many talented young persons. In order to optimize chances for success, young faculty should clearly define their goals, carefully negotiate the terms of their employment, practice sound principles of time management, identify a mentor, and develop a focused research agenda. PMID- 2309743 TI - Fever, rash, and lung infiltrates in a 47-year-old woman. PMID- 2309744 TI - Functional laryngeal obstruction: a somatization disorder. PMID- 2309745 TI - Use of immunosuppressive agents in the treatment of severe ocular and vascular manifestations of Cogan's syndrome. PMID- 2309747 TI - Hypothyroidism and functional bowel disease. PMID- 2309746 TI - A structurally aberrant immunoglobulin paraprotein in a patient with multiple myeloma and corneal crystal deposits. PMID- 2309748 TI - A hyperdense intracranial metastatic carcinoid tumor. PMID- 2309749 TI - Cocaine-associated rhabdomyolysis and hemoptysis mimicking pulmonary embolism. PMID- 2309750 TI - Syncope and human immunodeficiency virus disease in the elderly. PMID- 2309751 TI - Bacteremia in patients with acquired immunodeficiency syndrome. PMID- 2309752 TI - Transabdominal and transcervical chorionic villus sampling: efficiency and risk evaluation of 2,411 cases. AB - Efficacy and risks of transcervical and transabdominal chorionic villus sampling (CVS) methods were evaluated in 1,501 and 910 cases, respectively. We reported a success rate of more than 99% for both sampling procedures and obtained an adequate amount of chorionic tissue in more than 96% of cases on the first attempt. However, the transcervical method was more difficult to learn and was contraindicated by a higher number of unfavorable clinical and anatomical conditions. Transabdominal sampling proved to be a less time-consuming procedure and could also be used after the 12th week of gestation. Bleeding/spotting (10.1%) and uterine cramping (2.5%) were the most frequent early complications following transcervical and transabdominal sampling, respectively. Uterine infection was rare (0.13%) and was reported only after cervical aspiration. No significant effects on fetal growth, preterm delivery, placenta disorders, congenital defects, and perinatal mortality following transcervical and transabdominal sampling, and for both procedures total fetal loss rate was less than 4%. This experience suggests that transabdominal needle sampling is the method of choice; however, transcervical aspiration appears more likely to succeed in a limited number of well-defined conditions. PMID- 2309753 TI - Current assessment of fetal losses as a direct consequence of chorionic villus sampling. AB - Chorionic villus sampling has been developed as a method of first trimester prenatal diagnosis. In order to evaluate this new approach, accurate risk figures for the procedure must be obtained. This has been difficult for a number of reasons, including establishment of baseline fetal loss rates in the first trimester, procedural "learning curves," and reporting biases. This review will discuss these problems and use data from the chorionic villus sampling program at the University of California, San Francisco, to illustrate difficulties in data interpretation. PMID- 2309754 TI - Fetal loss rate after chorionic villus sampling and subsequent amniocentesis. AB - Here we review a group of 82 patients who underwent both chorionic villus sampling (CVS) and amniocentesis in the same pregnancy during the period May 1984 May 1988. A fetal loss rate of 2.5% is documented. This is not essentially different from the sum of fetal loss rates following each of the procedures separately (CVS, 1.9%; amniocentesis, 1.0%) established during the same period. PMID- 2309755 TI - Direct chromosome preparation and culture using chorionic villi: an evaluation of the two techniques. AB - We present a comparison between direct chromosome preparation and cell culture for first trimester fetal chromosome study using chorionic villi. The 2 techniques have advantages and disadvantages and are demonstrated to be appropriate for routine diagnostic work. The combined use of both methods may optimize the quality of the chromosome study and minimize the possibility of false-positive and false-negative findings. PMID- 2309756 TI - Chromosome abnormalities in older women by maternal age: evaluation of regression derived rates in chorionic villus biopsy specimens. AB - Maternal age-specific rates of chromosome abnormalities in women undergoing chorionic villus sampling (CVS) were evaluated. These were rates derived from regression equations of the form rate = ln(b[age] + c) where age varied from 35 to 48 years; and b and c are parameters. For Down syndrome (47, + 21), b = 0.29 and c = -15.53; for other nonmosaic abnormalities, b = 0.25 and c = -14.11; and, for all abnormalities, b = 0.27 and c = -14.22. The predicted rates per 1,000 varied, respectively, from 4.2, 4.6, and 8.8 at age 35 years to 180.0, 120.0, and 300.0 at age 48 years. The predicted numbers of abnormalities were compared with those observed in an overlapping data set reported in the literature. For 47, + 21, the ratio of observed (O) to expected (E) numbers was 54/56.4 = 0.96, suggesting that these rates are at least not grossly erroneous. For non-47, + 21 chromosome abnormalities, the ratio of O to E was 66/51.1 = 1.29. The possibility of geographic variation in rates of non-47, + 21 chromosome abnormalities cannot be dismissed. Finally, if 1) the regression derived rates are correct, 2) there is no difference in selective loss of chromosome abnormalities between younger and older mothers, and 3) the ratio of rates at ages 35 and 40 years to those in the women of all ages are the same for all abnormalities at CVS as for 47, + 21 in live births, then the proportion of all women with viable conceptuses at time of CVS who have an embryo or fetus with cytogenetic abnormality is 3.8-4.4 per 1,000 conceptuses. PMID- 2309757 TI - Prospective study of amniocentesis performed between weeks 9 and 16 of gestation: its feasibility, risks, complications and use in early genetic prenatal diagnosis. AB - This paper demonstrates that the outcome of amniocenteses performed between the 9th and the 14th weeks is similar to that of amniocenteses performed between the 15th and 20th weeks. We have performed and prospectively followed 615 amniocenteses between the 9th and 16th weeks of gestation. The outcome, risks, and complications are similar to those of amniocenteses at the usual time (after 15 weeks) and to the other groups of early amniocentesis (before 15 weeks). Early amniocentesis differs from amniocentesis at the usual time in that it carries higher rates of fetal losses and of amniotic fluid leakage, more confined cytogenetic abnormalities, and an increased number of patients who have the procedure postponed. Two cultures (0.32%) failed to produce results, 595 (96.7%) samples were obtained at the first tapping, 20 (3.3%) at the second attempt. alpha-Fetoprotein levels reach their maximum at 13 weeks. Amniocenteses between 15 and 16 weeks (293, or 47%) constitute the control group, those between 9 and 14 weeks (322) the experimental group. Early amniocentesis appears to be a safe early genetic prenatal diagnosis technique, an alternative to chorionic villi sampling. PMID- 2309758 TI - Preimplantation sexing and diagnosis of hypoxanthine phosphoribosyl transferase deficiency in mice by biochemical microassay. AB - Hypoxanthine phosphoribosyl transferase (HPRT)-deficient male embryos derived from heterozygous (carrier) female mice were diagnosed by biochemical microassay of X-chromosome-coded HPRT activity in a single cell taken from the 8-cell embryo or in 5-10 cells sampled from the blastocyst. In the latter procedure, carrier female blastocysts could also be distinguished from affected males, and normal males and females, as having intermediate HPRT activity in the sampled trophectoderm cells. During the assay procedures, the operated preimplantation embryos were cultured. They were then transferred, in batches as diagnosed, to recipient females. The resulting fetuses were sexed by gonad morphology and assayed for HPRT activity. All those identified as HPRT-negative embryos by biopsy at the 8-cell or blastocyst stages were indeed HPRT-negative males. The heterozygous females were also correctly identified by the trophectoderm biopsy procedure. The sex of an embryo can also be diagnosed by HPRT activity dosage in a single blastomere taken from 8-cell embryos from a normal mating and cultured for 12 hours before assay. Both X chromosomes are active in female morulae and the blastomeres sampled from female preimplantation embryos have twice the X coded HPRT activity compared to those from the male embryos. The accuracy of this procedure for sexing was again verified by transfer of the putative male and putative female embryos into recipient females. PMID- 2309759 TI - Legal and ethical implications of fetal diagnosis and gene therapy. AB - With rapidly expanding capabilities in prenatal diagnosis and treatment resulting from new technologies, the medical profession is increasingly being confronted with legal uncertainties and ethical dilemmas. In this paper, we review current acceptable standards of care in the area of medical practice as related to genetic counseling and prenatal diagnosis. We emphasize that any attempts at therapeutic genetic intervention be carried out only 1) when there is reasonable scientific evidence that it will cure or prevent a disabling disease, and b) with the informed, voluntary, competent, and understanding consent of the individuals involved. PMID- 2309760 TI - Spondylocostal dysostosis: dominant type. AB - We report on a father and daughter who have spondylocostal dysostosis. The girl's ribs are more severely abnormal than those of the 2 previously reported cases of dominant spondylocostal dysostosis and are rather suggestive of the autosomal recessive type. The differential diagnosis of both forms is discussed. PMID- 2309761 TI - Transcobalamin II deficiency presenting with methylmalonic aciduria and homocystinuria and abnormal absorption of cobalamin. AB - An infant with deficiency of transcobalamin II (TCII) presented with virtually complete failure to thrive and life-threatening pancytopenia. Methylmalonic acid and homocystine were found in the urine. The concentration of B12 in the serum was 26 pg/ml. Fibroblasts derived from the patient failed to take up labeled cobalamin in the absence of a source of TCII. Uptake was normal in the presence of TCII. Treatment with parenteral cobalamin reversed the clinical and hematological manifestations of the disease but she developed glossitis when the interval between injections was lengthened. Intestinal absorption of 57Co cobalamin was less than 1% and remained abnormal when highly purified human intrinsic factor was given along with the labeled B12. Absorption improved when the labeled B12 was given together with rabbit TCII. The data suggest that TCII as well as intrinsic factor is required for transport of cobalamin from the intestine to the blood. PMID- 2309762 TI - Mirror polydactyly: pathogenesis based on a morphogen gradient theory. AB - We report on an infant with 7 toes of the left foot in a mirror configuration in association with ipsilateral duplication of the calcaneus and fibula, tibial aplasia, femoral hypoplasia, and a teratomatous sacrococcygeal tumour. The possible pathogenetic mechanisms leading to this limb abnormality are discussed with special emphasis on a field morphogen gradient hypothesis. PMID- 2309763 TI - Carpenter syndrome: marked variability of expression to include the Summitt and Goodman syndromes. AB - Here we report on two sibs with Carpenter syndrome showing marked intrafamilial variability. One patient had craniosynostosis of the sagittal suture, normal intelligence, and no abnormalities of hands and feet. The second patient had polysyndactyly of hands and feet, normal intelligence, and no craniosynostosis. The diagnosis of Carpenter syndrome was made after the second affected child in the family was born. This report emphasizes previous suggestions that acrocephalopolysyndactyly, type II, has variable clinical expression. It is suggested that polysyndactyly of feet is not an absolute requisite for the diagnosis of Carpenter syndrome. This allows the inclusion of Summitt and Goodman syndromes within the clinical spectrum of this disorder. PMID- 2309764 TI - Congenital hypoplastic (Diamond-Blackfan) anemia in seven members of one kindred. AB - Congenital hypoplastic (Diamond-Blackfan) anemia is a rare macrocytic anemia, generally presenting during infancy or childhood. The condition usually occurs sporadically or in a pattern consistent with autosomal recessive inheritance, although autosomal dominant transmission has been proposed in some kindreds. We report the largest known kindred of congenital hypoplastic anemia, with at least 7 affected individuals over 3 generations, and propose that studies of this kindred may be useful for identifying the mechanism by which their genetic abnormality results in congenital hypoplastic anemia. Erythropoietic investigations on relatives show no inhibitors of erythropoiesis in serum, T lymphocytes, or macrophages. Their erythroid progenitor cells (CFU-E and BFU-E) were generally quantitatively normal, and were capable of rapid proliferation, as judged by cell-cycle shortening. However, their erythroid progenitors displayed a relative insensitivity to recombinant erythropoietin, and produced relatively few normoblasts per erythroid progenitor cell. We propose that these and subsequent studies may be helpful in selecting candidate genes responsible for the molecular defect in this kindred. PMID- 2309765 TI - Comparison of education and occupation of adults with achondroplasia with same sex sibs. AB - We compared the education and occupation of 20 adults with achondroplasia with their same-sex sibs. While the mean number of years of formal education reported by affected males and females was comparable to that of their same-sex sib, we found differences in the level of occupation between the groups. In general, affected females had a significantly lower occupational level compared to their unaffected sisters. In males and females the number of years of formal education and whether or not individuals had achondroplasia were the 2 most important factors determining occupational level when contrasting affected persons with their unaffected sibs. Education alone accounted for 28 and 42% of the observed variance in occupational level, respectively, for females and males. PMID- 2309766 TI - Distal deletion of the short arm of chromosome 6. AB - We report on a patient with deficiency of distal 6p and compare the clinical and cytogenetic findings in this child with those of three previously reported patients who had similar deletions. Distal del(6p) appears to be associated with a relatively non-specific phenotype, with the possible exception of unusual congenital eye findings. This apparent association of congenital eye defects with distal del(6p) was supported by comparison with patients having other deletions of chromosome 6, particularly those with ring chromosome 6. PMID- 2309767 TI - Aspartoacylase deficiency and Canavan disease in Saudi Arabia. AB - We found defective aspartoacylase activity in fibroblasts cultured from 12 patients with leukodystrophy clinically diagnosed as spongy degeneration of the brain (Canavan disease), three confirmed by brain biopsy. The activity of aspartoacylase ranged between 1 and 13% of two groups of control individuals, normals, and those with other leukodystrophies. The present report confirms the study of Matalon et al. [1988] in a totally different ethnic group and provides independent verification that aspartoacylase activity is the first documented specific biochemical marker in Canavan disease and plays an important role in pathogenesis. Considering that only some 75 cases had been reported up to 1982, our group of 12, accumulated within 3 years, is inordinately large and suggests that Saudi Arabia provides a promising venue in which to study the biochemical and molecular genetics of Canavan disease. PMID- 2309768 TI - Nonimmunologic hydrops fetalis: an etiopathogenetic approach through the postmortem study of 59 patients. AB - Aiming at increasing our understanding of the various causative factors of nonimmunologic hydrops fetalis (NIHF) and their pathogenetic mechanisms, we have reviewed 59 cases of this condition from a total number of 4,175 pediatric post mortem studies performed at the Department of Pathology of the Hospital La Paz from 1967 to 1987. We found eight cases (13.5%) without clinical, biochemical, or post-mortem findings justifying the development of hydrops fetalis, seven cases (12%) associated with certain pathologic findings that by themselves do not explain the development of hydrops and, finally, 44 cases (74.5%) in whom pathological findings may explain the development of the condition. Notwithstanding the etiological diversity of this last group, in 31 of these cases (70%), some common pathogenetic features may be recognized, basically a failure of the right ventricle of the heart in the fetus or newborn, due to a primary heart condition, to intracardiac tumors, or to obstructive phenomena at the level of the right venous drainage. In our opinion, whenever NIHF is diagnosed or suspected, causes of right cardiovascular failure should be investigated, since about 50% of all cases seem to be due to this pathogenetic mechanism. PMID- 2309769 TI - Mild form of Jeune syndrome in two sisters. AB - Jeune syndrome is characterized by respiratory distress, osseous dysplasia, and short stature. Patients generally die during the first months of life. However, some cases with milder clinical manifestations have been described; these cases show characteristic renal involvement of different severity. The authors report on two cases of the mild form of Jeune syndrome in sisters. PMID- 2309770 TI - Proteus syndrome: course of a severe case. AB - We report on the course of a 4 1/2-year-old boy with Proteus syndrome who was first described 3 years ago. Details are given on the phenotypic changes, the complications of corrective surgery on tissue overgrowth, and the development of a mesothelioma of the tunica vaginalis of the testis. PMID- 2309771 TI - Chromosome 7 abnormalities in parents of children with holoprosencephaly and hydronephrosis. AB - At least nine cases of holoprosencephaly (HPE) found in patients with confirmed loss of 7q34----7qter or 7q36----7qter have been reported in the literature. In the present report, balanced rearrangements involving chromosome 7q [inv(7)(p22.1q34) and t(4;7)(q31;q36)] were shown in two mothers examined after the birth of their non-karyotyped infants with HPE and hydronephrosis. In both cases, del(7q) was the most probable imbalance. The available data confirm the association between HPE and del(7q). Predominance of cyclopia and cebocephaly, the severest forms of HPE, suggests that del(7q) may be an important factor in arresting prosencephalon development at the earliest stages. PMID- 2309773 TI - Bannayan-Riley-Ruvalcaba syndrome: renaming three formerly recognized syndromes as one etiologic entity. PMID- 2309772 TI - Craniosynostosis in the Ullrich-Turner syndrome. PMID- 2309774 TI - Mutation rate estimate in hereditary cutaneous malignant melanoma/dysplastic nevi. PMID- 2309775 TI - Reply: the dysplastic nevus "syndrome" is not a dichotomic, but a continuous phenotype. PMID- 2309776 TI - Excess of females in chromosomally normal spontaneous abortuses. PMID- 2309777 TI - Chromosome abnormality in Kallmann syndrome. AB - We report on an individual with Kallman syndrome (KS) and a balanced de novo translocation (7;12)(q22,q24). None of 6 full sibs, 3 half-sibs, or parents have KS or this chromosome translocation. This is the only known report of KS with a chromosome abnormality. This may represent a spurious association or genetic heterogeneity vis-a-vis the reported linkage of KS to the steroid sulphatase gene on the X chromosome. The pathophysiology and genetics of KS are discussed. PMID- 2309778 TI - Cytogenetic and molecular study of Angelman syndrome. AB - Six patients, including two sibs, with Angelman syndrome (AS; three females and three males, aged 11 to 18 years) were studied cytogenetically. Molecular analysis was also performed. Using high-resolution banding technique, we detected a microdeletion in the proximal region of chromosome 15q in four cases. The deleted segment was heterogenous between these patients, and the common deleted region appeared to be 15q11.2. Four patients with deleted 15q were all sporadic cases, whereas in the sib cases we could not detect a visible deletion in the long arm of chromosome 15. However, there was no clinical difference between sporadic cases and sib cases. Densitometric analysis of autoradiographic bands of Southern hybridization using two DNA segments, pML34 and pTD3-21, as probes demonstrated that two patients had only one copy for each of the probes. In the remaining four patients, including the sibs, two copies of each sequence were retained. The probes used here detect a molecular deletion in most Prader-Willi syndrome patients. Thus the segment causing AS is localized adjacent to the critical segment of Prader-Willi syndrome. There seemed to be heterogeneity for the molecular deletion within AS individuals. PMID- 2309780 TI - Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences. AB - It has recently been shown that apparently similar deletions of chromosome 15q occur commonly in the Prader-Willi and Angelman syndromes. The distinctness of the syndromes suggests that the deletions are not identical. To address this possibility, the specific bands involved and the sizes of the deletions were compared in seven patients with Prader-Willi syndrome and 10 patients with Angelman syndrome using high-resolution G-, Q-, and fluorescent R-banding techniques. The parental origin of the nine cases of Angelman syndrome for which parents were available for study was determined. The same proximal band was deleted (q11.2) in both syndromes. In general, the deletion in patients with Angelman syndrome was larger, though variable, and included bands q12 and part of q13. All of the studied deletions in patients with Angelman syndrome were of maternal origin. This contrasts with the predominant paternal origin of the deletion in patients with Prader-Willi syndrome. Two possible reasons for these observations are postulated: 1) the deleted regions are different at the cytologic and/or molecular level because of different exchange points in meiosis in males and females or to different mechanisms of breakage in males and females, resulting in differing breakpoints; 2) the deleted regions are essentially the same, but differential expression of the genes in the homologous chromosome 15 has occurred (imprinting). PMID- 2309779 TI - Prader-Willi syndrome: current understanding of cause and diagnosis. AB - Prader-Willi syndrome (PWS) is characterized by hypotonia, obesity, hypogonadism, short stature, small hands and feet, mental deficiency, a characteristic face, and an interstitial deletion of the proximal long arm of chromosome 15 in about one-half of the patients. The incidence is estimated to be about 1 in 25,000, and PWS is the most common syndromal cause of human obesity. DNA abnormalities, usually deletions or duplications of chromosome 15, have been identified in individuals with PWS with or without recognizable chromosome 15 deletions. Paternal origin of the chromosome 15 deletion by cytogenetic and DNA studies has been found in nearly all PWS individuals studied. No cytogenetic evidence for chromosome breakage has been identified, although an environmental cause (e.g., paternal hydrocarbon-exposed occupations) of the chromosome 15 abnormality has been proposed. PWS patients with the chromosome 15 deletion are more prone to hypopigmentation compared with PWS individuals with normal chromosomes, but no other clinical differences are consistently identified between those with and without the chromosome deletion. Anthropometric, dermatoglyphic, and other clinical findings indicate homogeneity of PWS patients with the chromosome deletion and heterogeneity of the nondeletion patients. A review of our current understanding of the major clinical, cytogenetic, and DNA findings is presented, and clinical manifestations and cytogenetic abnormalities are summarized from the literature. PMID- 2309781 TI - Maternal origin of 15q11-13 deletions in Angelman syndrome suggests a role for genomic imprinting. AB - Six persons with the classical Angelman syndrome (AS) phenotype and de novo deletions of chromosome 15q11-q13 were studied to determine the parental origin of the chromosome deletion. Four of the 6 patients had informative cytogenetic studies and all demonstrated maternal inheritance of the deletion. These findings, together with other reported cases of the origin of the chromosome 15 deletion in AS, suggest that deletion of the maternally contributed chromosome leads to the AS phenotype. This contrasts with the Prader-Willi syndrome (PWS) in which a similar deletion of the paternally contributed chromosome 15 is observed. In deletion cases, a parental gamete effect such as genomic imprinting may be the best model to explain why apparently identical 15q11-q13 deletions may develop the different phenotypes of AS or PWS. PMID- 2309782 TI - Segregation distortion in inheritance of progressive rod cone degeneration (prcd) in miniature poodle dogs. AB - Segregation distortion was observed in inheritance of progressive rod-cone degeneration (prcd) in a colony of Miniature Poodle dogs. Breeding results, from both retrospective records and prospectively planned matings, were classified into five mating types: (1) affected to affected, (2) homozygous normal sire to any dam, (3) heterozygous to heterozygous, (4) heterozygous sire to affected dam, and (5) affected sire to heterozygous dam. For all but the last category, results were in accord with mendelian expectations for autosomal-recessive inheritance. However, litters of mating type 5 had fewer affected pups (20/77) than expected. The observed segregation ratio for this mating type (0.26) was significantly (P less than 0.001) less than the expected (0.50). The segregation distortion could not be accounted for by either pre- or postnatal loss of affected pups, as litter size and litter survivability were uniform among litters of different mating types. Either the prcd locus, or a linked locus, would appear to influence either gametic or zygotic fitness in the heterozygous mother. Comparison is drawn to the inheritance of retinitis pigmentosa in humans, in which decreased segregation ratios are also recognized. PMID- 2309783 TI - Oral-facial-digital syndrome type VI (Varadi syndrome): further clinical delineation. AB - Cerebellar anomalies are consistent findings in patients with the oral-facial digital syndrome type VI (Varadi syndrome) in addition to variable facial and oral changes, and polysyndactyly of hands and feet. We report 3 unrelated patients with this entity who have a hypoplastic cerebellar vermis shown by magnetic resonance imaging (MRI), as well as clinical signs of cerebellar defect. Polydactyly of the hands is characterized by a central Y-shaped metacarpal. Clinically recurrent episodes of tachypnea and hyperpnea are remarkable. Postnatal growth is delayed with short stature in all 3 patients possibly due to growth hormone deficiency in one of them. In contrast to reported patients who are all severely mentally retarded, one of our patients is of normal intelligence. Type VI oral-facial-digital syndrome is an autosomal-recessive trait and may be detected prenatally. PMID- 2309784 TI - Mild phenotypic abnormalities in combined del 9p2 and dup 3p2. AB - Clinically recognizable syndromes have been reported in association with both del 9p2 and dup 3p2. We report on a girl with combined del 9p2 and dup 3p2 with manifestations of both syndromes but who is less severely affected than one would expect. PMID- 2309785 TI - Adenine nucleotides, serotonin, and aggregation properties of platelets of blue foxes (Alopex lagopus) with the Chediak-Higashi syndrome. AB - Bleeding times, concentrations of serotonin in whole blood, and concentrations of adenine nucleotides as well as aggregation properties of platelets were examined in 18 blue foxes with Chediak-Higashi-like syndrome (CHS) and 16 controls. A claw of each ketamine-sedated fox was cut until bleeding started and the bleeding time was recorded as the time from the first to the last drop. The bleeding time was greatly increased in CHS foxes. Platelet counts of CHS foxes were normal, but aggregation induced by adenosine diphosphate (ADP), serotonin, collagen, and arachidonate was impaired. Adrenaline and serotonin was impaired. Adrenaline and serotonin potentiated the aggregatory effect of ADP on control as well as on CHS platelets. The mean concentration of ADP in CHS platelets was about one-third that in controls, whereas adenosine triphosphate (ATP) was approximately one-half that in controls. Serotonin could not, in most cases, be detected in blood of CHS foxes. These findings suggest that the prolonged bleeding time in the CHS foxes is, at least partly, due to a storage pool deficiency. The drastically reduced, and in some cases absent, aggregation of CHS platelets in response to arachidonate suggests that defective arachidonate metabolism contributes to the impaired hemostasis. PMID- 2309786 TI - Previously unrecognized congenital progeroid disorder. AB - We report on a 5-year-old girl with a progeroid disorder and compare her to a previously reported woman now in her forties, whom she resembles to a striking degree. Common manifestations include pre- and post-natal growth retardation, markedly diminished subcutaneous fat, wrinkled skin, abnormally scant hair growth, hypoplastic distal phalanges with hypoplastic nails, umbilical hernia, large open anterior fontanelle, and normal cognitive and motor development. Both patients have had a prematurely aged appearance since birth. These 2 patients appear so different from previously reported patients with progeroid disorders that they may represent a separate entity. PMID- 2309787 TI - A "new" skeletal dysplasia in two unrelated boys. AB - We report on 2 unrelated boys with similar physical and radiographic findings that may represent a "new" skeletal dysplasia. Findings in common include early speech delay, short stature, frontal bossing with a depression over the metopic suture, a narrow nasal root with beaked nose, midfacial hypoplasia with relatively prominent eyes, and brachydactyly with blunt fingers. Radiographic findings include mild irregularities of the vertebral bodies, hypoplasia of the odontoid process, short phalanges with increased distal width, coning and sclerosis of several epiphyses, and overtubulation of the long bones. Although these patients share some manifestations with the floating-harbor syndrome (Robinson et al.: J Pediatr 113:703-706, 1988), their radiographic changes are distinctive and are not suggestive of a recognized skeletal dysplasia syndrome. PMID- 2309788 TI - Neural tube defects: are neurulation and canalization forms causally distinct? AB - Neural tube defects (NTD) may be separated according to the overall location and probable embryological origin into 2 groups: upper or neurulation defects, and lower or canalization defects. Evidence as to whether these 2 forms are causally related or distinct was sought from 2 sources. Families with more than one NTD individual were studied to examine whether there was concordance within sibships for these 2 types of lesion. Seven of the 38 sibships were discordant (18%). Eight of the 10 cases of NTD that had arisen despite maternal periconceptional vitamin supplementation were neurulation defects and 2 were canalization defects. Both observations suggest that upper and lower types of NTD are causally related, and offer no support for the suggestion that they are distinct. PMID- 2309789 TI - Apparent Smith-Lemli-Opitz syndrome in a child with a previously undescribed form of mucolipidosis not involving the neurons. AB - A diagnosis of Smith-Lemli-Opitz syndrome was made shortly after birth in a small for-dates infant, on the basis of a characteristic face, penoscrotal hypospadias, bilateral postaxial hexadactyly, and bilateral syndactyly of toes 2-3. The clinical course was marked by failure to thrive, severe delay, refractory myoclonic jerks beginning at age 2 months, and increasing hepatosplenomegaly. He developed corneal clouding and increased gingival hypertrophy and died at age 18 weeks. Autopsy disclosed widespread storage of mucopolysaccharides and lipids within the macrophages and, to a lesser extent, parenchymal cells, of all organ systems. There was extensive demyelination of the cerebral white matter, and dystrophic calcification in the cerebrum, cerebellum, and brainstem. There was no evidence of primary neuronal involvement in the storage. Although the chance concurrence of 2 uncommon diseases is rare, a causal link between the clinical anomalies and the storage disorder cannot be argued convincingly on the basis of one case. Careful pathologic studies of other children who die with clinical signs compatible with Smith-Lemli-Opitz syndrome are indicated. PMID- 2309791 TI - Pathogenesis of the lethal multiple pterygium syndrome. AB - We present autopsy studies in 4 unrelated fetuses with the lethal multiple pterygium syndrome (LMPS) with special emphasis on the neuromuscular system. The data suggest that LMPS combines the manifestations of a jugular lymphatic obstruction sequence with those of an early severe fetal akinesia sequence. The jugular lymphatic obstruction sequence with resultant edema and cystic hygroma colli causes fetal lethality usually in the second trimester of pregnancy. Generalized amyoplasia appears to be an important mechanism in the pathogenesis of fetal akinesia as part of LMPS and is not associated with dysgenesis or degeneration of the central nervous system (CNS) but is apparently the result of an early fetal muscular "dystrophy." We propose a genetically determined insult affecting the early embryonic development of both lymph vessels and muscles as the basic defect in LMPS. Placental structure, studied in all 4 cases, demonstrated that triploidy-like placental lesions are specific to LMPS. The present findings suggest that LMPS may be a less heterogeneous entity than previously proposed. PMID- 2309790 TI - Familial renal hypophosphatemia, minor facial anomalies, intracerebral calcifications, and non-rachitic bone changes: apparently new syndrome? AB - We report on two brothers with renal hypophosphatemia, intracerebral calcifications, minor facial anomalies, and short distal phalanges. The children presented with recurrent dental abscesses; one had premature closure of the anterior fontanelle. Biochemical findings included hypophosphatemia and elevated serum alkaline phosphatase with normocalcemia. Blood levels of parathyroid hormone, 1,25(OH)2 and 25(OH) vitamin D levels were normal; TRP (the fractional tubular reabsorption of PO4) and TmP/GFR (the tubular maximum rate of PO4 reabsorption in relation to GFR) were low. Both parents had a normal serum phosphate and brain CT scan without evidence of calcifications. This apparently new syndrome of renal hypophosphatemia associated with intracerebral calcifications appears to be inherited as either an autosomal recessive or an X linked trait. PMID- 2309792 TI - Hypomelanosis of Ito--a nonspecific marker of somatic mosaicism: report of case with trisomy 18 mosaicism. AB - We report on a patient with hypomelanosis of Ito (HI), developmental delay, recurrent pneumonia, and facial asymmetry. Chromosome analysis done on blood and on one of three skin biopsies showed trisomy 18 mosaicism. This is the first report of HI associated with trisomy 18 mosaicism. This neuroectodermal disorder appears to be a nonspecific manifestation of chromosome mosaicism. PMID- 2309794 TI - Neuroblastoma in a child with Wiedemann-Beckwith syndrome. AB - We report on a patient with Wiedemann-Beckwith syndrome (WBS) who developed abdominal neuroblastoma. Although WBS patients are known to have a higher incidence of embryonal tumors, this is only the 4th known case of neuroblastoma associated with this syndrome. Chromosomes on peripheral lymphocytes and tumor cells were normal. Children with WBS should be screened for a variety of embryonal neoplasms, not only Wilms tumor. PMID- 2309793 TI - Stepwise oligogenic segregation and linkage analysis illustrated with dopamine beta-hydroxylase activity. AB - A stepwise oligogenic method is developed that can be used to adjust the phenotype of a quantitative trait for the effects of a previously identified single-locus component. This method assumes that a single-locus component can be adequately identified through the use of segregation and/or linkage analysis under a 1-locus model and that the variation due to that locus can be removed from the phenotype leaving a residual that can be parameterized in terms of an additional single-locus component. Segregation and/or linkage analysis can then be used in an attempt to identify an additional single-locus component in the residual phenotype. This stepwise process can be repeated until no further single locus effects are identified. The method is illustrated using family data on the specific activity of dopamine-beta-hydroxylase (DBH), which a number of studies have suggested may be due either to the combined effects of single-locus and multifactorial components or to the combined effects of 2 loci. PMID- 2309795 TI - Myelodysplasia and leukemia syndrome with monosomy 7: a genetic perspective. AB - Acquired monosomy 7 is a frequent finding in myelodysplastic syndromes, including acute myelogenous leukemia. A subset of these patients has been described with an apparently distinct condition: myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7). We report 2 brothers, 3 and 5 years of age, with MLSM7 and review other reports of familial occurrence. Genetic factors appear to be important in the cause of MLSM7, but the reported families do not fit neatly into any monogenic pattern. Recognition of the frequently familial nature of this condition requires hematological evaluation and genetic counseling for the families of patients with MLSM7. PMID- 2309797 TI - 'Protect nurses from needles,' OSHA is told. PMID- 2309796 TI - Acrocallosal syndrome. AB - Acrocallosal syndrome is an autosomal recessive disorder of brain malformation and complex polydactyly. We report on an additional patient with this disorder. It is suggested that increased birth weight and cerebellar hypoplasia occur in acrocallosal syndrome. The finding of an extra bone within the anterior fontanel in our patient suggests similarity to the Xt mouse mutant, which is homologous to Greig syndrome in man. This provides additional support for the hypothesis of allelism of the Greig and acrocallosal syndromes. PMID- 2309798 TI - Managing fatigue. PMID- 2309799 TI - The fairness doctrine. PMID- 2309800 TI - Clues: bruised, torn skin. PMID- 2309801 TI - 'Maid to order'? PMID- 2309802 TI - Myth breaker. PMID- 2309803 TI - Agency nurse vs. IRS: are you an employee, an independent contractor, or both? PMID- 2309804 TI - RNs urge AIDS curriculum. PMID- 2309805 TI - 56 ways to get certified. PMID- 2309806 TI - Midwest jobfocus. Grand Central, USA. PMID- 2309807 TI - Michigan jobfocus. Making it in Michigan. PMID- 2309808 TI - "Caregiver" system pays for a caregiving corporation. PMID- 2309809 TI - Military nurse chiefs fight for federal nursing college. PMID- 2309810 TI - Clinical guides to preventing ethical conflicts between pregnant women and their physicians. AB - We provide a justification for preventive ethics in obstetric practice. Four clinical guides to resolving ethical conflicts between pregnant women and their physicians can be identified: (1) informed consent as an ongoing dialogue between the pregnant woman and her physician, (2) negotiation as a clinical strategy, (3) respectful persuasion as a clinical strategy, and (4) the proper use of ethics committees. PMID- 2309811 TI - The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? AB - The question of whether the HELLP syndrome exists as a distinct entity or is part of a spectrum of pregnancy complications, which have in common hemolysis, elevated liver enzymes, and thrombocytopenia, has long been a source of speculation and debate among obstetricians and internists. A review of the literature indicates a definite need for a uniform definition, diagnosis, and management of this syndrome. Patients manifesting this syndrome usually are seen before term (less than 36 weeks' gestation) complaining of malaise (90%), epigastric or right upper-quadrant pain (90%), and nausea or vomiting (50%), and some will have nonspecific viral-syndrome-like symptoms. Hypertension and proteinuria may be absent or slight. Thus some of these patients may have a variety of signs and symptoms, none of which are diagnostic of classic preeclampsia. In consideration of the high maternal and perinatal mortality and morbidity reported with the presence of this syndrome, I recommend that all pregnant women having any of these symptoms should have a complete blood cell count with platelet and liver enzyme determinations irrespective of maternal blood pressure. PMID- 2309812 TI - Infections complicating low-risk cesarean sections in community hospitals: efficacy of antimicrobial prophylaxis. AB - A prospective study of women with low-risk cesarean sections was conducted in four community hospitals to determine the frequency of postoperative infections and identify factors predisposing to endometritis and wound infection. Low-risk cesarean section was defined as a scheduled procedure without an urgent indication, with any duration of ruptured membranes being less than or equal to 12 hours. In a cohort of 1863 patients, 26 (1.4%) developed endometritis and 21 (1.1%) had wound infections. Primary cesarean section was associated with endometritis in the cohort (p less than 0.01) and in a retrospective study with the same cases as in the cohort (p = 0.01). Absence of antibiotic prophylaxis was associated with endometritis (p less than or equal to 0.013) or endometritis with wound infection (p less than 0.01) in both studies. Without prophylaxis 37 such infections occurred in 957 (3.7%) women; with prophylaxis eight infections occurred in 906 (0.9%) women. Routine timely antibiotic prophylaxis in low-risk cesarean sections could lead to an annual national savings of approximately $9 million. PMID- 2309813 TI - Treatment-dependent and treatment-independent pregnancy among women with periadnexal adhesions. AB - In an attempt to evaluate the efficacy of salpingoovariolysis we studied 147 women who were found to have periadnexal adhesions on laparoscopic examination. Among these women, 69 were treated by laparotomy and salpingoovariolysis and 78 were not treated. There was no significant difference between the degree of adhesions in the treated group and in the nontreated group. With the use of life table analysis, the cumulative pregnancy rate at 12 and 24 months follow-up was 32% and 45% in the treated group and 11% and 16% in the nontreated group, respectively (p less than 10(-6)). We suggest that although pregnancy might occur in infertile women who have periadnexal adhesions, treatment with salpingoovariolysis is associated with a higher pregnancy rate. PMID- 2309814 TI - Increased plasma levels of ED1+ cellular fibronectin precede the clinical signs of preeclampsia. AB - To evaluate alterations in fibronectin homeostasis in preeclampsia we measured the plasma concentrations of fibronectin bearing an extra type III domain in 33 preeclamptic and 36 control patients at varying gestational ages. This fibronectin variant is concentrated in the endothelium of blood vessels and has been shown to be released at sites of vascular injury. In addition, total circulating fibronectin levels, composed primarily of hepatic-derived fibronectin lacking the extra type III domain, were also determined. Significant elevations in the average circulating concentrations of fibronectin with an extra type III domain (5.5 micrograms/ml [95% confidence interval, 4.7,6.2] versus 3.2 micrograms/ml [95% confidence interval, 2.9,3.5]; p = 0.0001) as well as total fibronectin (387 micrograms/ml [95% confidence interval, 357,417] versus 327 micrograms/ml [95% confidence interval, 305,348]; p = 0.036) were observed in preeclamptic versus control patients. Significant elevations in fibronectin levels with an extra type III domain occurred in the first trimester before clinical evidence of preeclampsia. In addition, multivariate logistic regression demonstrated a 5.4-fold increase in the risk of preeclampsia with each 1 microgram/ml elevation in concentration of fibronectin with an extra type III domain. These findings lend support to the hypothesis that endothelial-vascular injury is a primary event in the genesis of preeclampsia. PMID- 2309815 TI - Labetalol pharmacokinetics in pregnancy-induced hypertension. AB - Pharmacokinetic parameters of oral labetalol were studied in eight women with pregnancy-induced hypertension in the third trimester of pregnancy. Labetalol exhibited rapid absorption; peak serum concentrations of 881 +/- 219 ng/ml occurred at 20 minutes after labetalol ingestion. The terminal elimination half life (mean, 1.7 +/- 0.27 hours) was found to be shorter than that reported for normotensive volunteers or nonpregnant hypertensive patients (mean, 6 to 8 hours). A mean apparent oral elimination clearance of 21.8 ml/min/kg compared favorably with that seen in other pregnant and nonpregnant populations. Food delayed the time to peak serum concentration to approximately 60 minutes. Labetalol was detected in fetal cord samples and amniotic fluid samples at concentrations approximately 50% and 16% that of simultaneous maternal vein samples, respectively. PMID- 2309816 TI - Proteinuria and outcome of 444 pregnancies complicated by hypertension. AB - The purpose of this study was to determine the role of proteinuria on pregnancy outcome in 444 hypertensive women with singleton pregnancies. The patients were divided into three hypertensive groups: 98 with chronic hypertension, 199 with nonproteinuric gestational hypertension, and 147 with proteinuric preeclampsia and chronic hypertension with superimposed proteinuric preeclampsia. The presence of increased proteinuria (greater than 0.3 gm/L) predicted an adverse pregnancy outcome. Furthermore, the majority of small-for-gestational-age infants occurred in the group with proteinuric preeclampsia (52%), whereas the rate of small-for gestational-age infants was 18% and 12% in the group with nonproteinuric gestational hypertension and chronic hypertension, respectively. The group with chronic hypertension did not show any increased risk for fetal outcome. Perinatal mortality rate was extremely poor in the group with proteinuric preeclampsia at 129 per 1000, four times higher than those of the other two groups. PMID- 2309817 TI - Maternal death caused by HELLP syndrome (with hypoglycemia) complicating mild pregnancy-induced hypertension in a twin gestation. PMID- 2309818 TI - Effects of birth weight and sociodemographic variables on mental development of neonatal intensive care unit survivors. AB - Neonatal intensive care unit survivors (N = 494) from 10 tertiary care centers were evaluated over the first 4 to 5 years of life to determine the relative contributions of birth weight and sociodemographic factors to mental development. Six sociodemographic factors were studied: sex, race, family income, and mother's marital status, age, and educational level; the last five factors also are known to be associated with premature birth. Mental development was measured with the Bayley Scales of Infant Development (12 to 24 months) and the Stanford Binet Intelligence Test (4 to 5 years). Each factor's influence was assessed by multivariate analysis. Birth weight had limited long-term implications; at 4 to 5 years, only infants with birth weights less than 1000 gm had significantly lower scores than those in other birth weight categories. Sociodemographic variables had a greater impact on mental development, with age-dependent differences found between nonwhite and white children and between children with mothers of low, medium, and high educational levels. PMID- 2309819 TI - Intrapartum asphyxia in the preterm fetus less than 2000 gm. AB - The incidence of intrapartum asphyxia in the preterm fetus less than 2000 gm (6%) is greater than that in the mature fetus (2%). Severe antepartum hemorrhage is the only clinical marker predictive of asphyxia in the preterm fetus. Marked deceleration patterns and particularly late decelerations may be of predictive value for asphyxia. However, many intrapartum asphyxial episodes are not identified on the basis of clinical observations. Consistent diagnosis of intrapartum asphyxia in the preterm fetus requires routine umbilical cord blood gas and acid-base assessment at delivery. PMID- 2309820 TI - Hypertriglyceridemia and hypoxemia in small-for-gestational-age fetuses. AB - Plasma triglyceride concentration and blood oxygen tension were measured in samples obtained by cordocentesis from 35 small- and 54 appropriate-for gestational-age fetuses at 18 to 36 weeks' gestation. In the appropriate-for gestational-age fetuses there was an exponential decrease in plasma triglycerides with gestation. Some small-for-gestational age fetuses were hypertriglyceridemic and the degree of this biochemical disturbance was significantly correlated with the degree of fetal hypoxemia. PMID- 2309821 TI - Relation of rate of urine production to oxygen tension in small-for-gestational age fetuses. AB - Hourly fetal urine production rate was determined by real-time ultrasonography immediately before cordocentesis for blood gas analysis in 27 small-for gestational-age fetuses at 20 to 37 weeks' gestation; in 14 cases there was associated oligohydramnios. The values were compared with those of 101 appropriate-for-gestational-age fetuses. The hourly fetal urine production rate was significantly lower in the small-for-gestational-age fetuses than in the appropriate-for-gestational-age fetuses. Furthermore, there was a significant correlation between the degree of decrease in urine production and both the degree of fetal hypoxemia and the degree of fetal smallness. There was no significant difference between the oligohydramnios and nonoligohydramnios groups in either the degree of decrease in urine production or the degree of fetal hypoxemia. PMID- 2309822 TI - Severe symmetric intrauterine growth retardation associated with the topical use of triamcinolone. AB - Triamcinolone acetonide, a fluorinated glucocorticoid, when given in large parenteral doses has produced structural anomalies and severe growth retardation in nonhuman primates. We present a case report of a gravid patient who applied 40 mg/day of triamcinolone cream because of atopic dermatitis from 12 to 29 weeks' gestation. The infant was symmetrically growth retarded, possibly from exposure to triamcinolone acetonide. There was no evidence of hypoxic, chromosomal, or infectious cause of the growth delay. PMID- 2309823 TI - Fetal assessment based on fetal biophysical profile scoring. III. Positive predictive accuracy of the very abnormal test (biophysical profile score = 0). AB - The relationship between complete absence of all components of the fetal biophysical profile score (biophysical profile score = 0) and adverse perinatal outcome was examined. Twenty-nine of 28,655 fetuses studied (0.092%) had a last biophysical profile score of 0; 48.3% of these perinates died (14 of 29 fetuses), the majority of whom (11 of 14) were stillborn, with death occurring as early as 30 minutes to as long as 11 days after the last test. Three asphyxia-related neonatal deaths occurred despite aggressive and immediate intervention. All survivors exhibited at least one of the five discrete markers used to assess perinatal morbidity. The positive predictive accuracy of a biophysical profile score of 0, with mortality and morbidity used as end points, was 100%. These data indicate the very abnormal fetal biophysical profile score to be a perinatal emergency. PMID- 2309824 TI - Evaluation of unfavorable histologic subtypes in endometrial adenocarcinoma. AB - A retrospective review of 388 patients who presented to the Mayo Clinic for treatment of endometrial carcinoma between 1979 and 1983 was performed and the surgical and pathologic observations were documented. An uncommon histologic subtype was detected in 52 patients (13%): 20 adenosquamous, 14 serous papillary, 11 clear cell, 7 undifferentiated. In contrast to the survival of patients with endometrioid lesions (92%), the overall survival in these patients was only 33%. Each of the individual abnormal histologic subtypes exhibited a survival of less than 50%. At the time of surgical staging, 62% of patients with unfavorable histologic subtypes had extrauterine spread of disease. Despite liberal utilization of postoperative adjuvant therapy in 42 of the 52 patients (81%), only 10% of these patients survived 5 years. Fifty-five percent had a component of recurrence outside of the abdominal/pelvic cavity. Subsequent treatment considerations should incorporate regimens addressing systemic and local tissue control. PMID- 2309825 TI - Use of serum CA 125 measurement in posttreatment surveillance of early-stage endometrial carcinoma. AB - Serum CA 125 levels were normal preoperatively in 123 of 125 (98.4%) patients with clinical and surgical stage I or II endometrial adenocarcinoma, and remained so in all patients who remained without evidence of either isolated vaginal recurrence or postoperative radiation enteritis. Recurrent disease developed in 13 patients. All of those who had pelvic (1), abdominal (4), or pulmonary (2) metastases had elevated serum CA 125 levels. None of the six patients with isolated vaginal recurrences had elevated CA 125 levels. Four patients had small bowel obstruction as a result of postoperative pelvic radiation, and all had elevated CA 125 levels during these episodes, although no evidence of recurrent disease was found during exploratory laparotomy for intestinal bypass. Serum CA 125 levels may have a role in the posttreatment surveillance of patients with early-stage endometrial carcinoma, but may be falsely elevated in the presence of severe radiation injury and at a normal level in the presence of isolated vaginal metastases. PMID- 2309826 TI - Pharmacokinetics of ritodrine administered intravenously: recommendations for changes in the current regimen. AB - We define the pharmacokinetics of ritodrine in 13 pregnant women who received the drug intravenously. With constant infusion of 50 micrograms/minute, steady state ritodrine concentrations reached 28 +/- 11 ng/ml (SD) with a range of 15 to 45 ng/ml. This wide variation is a result of differences in plasma clearance, which ranged from 1.0 to 3.3 L/min, mean 1.94 +/- 0.71 L/min. The apparent volume of distribution was 6.95 +/- 3.54 L/kg, indicating that ritodrine is extensively bound to extravascular tissue. When an infusion of ritodrine is stopped, plasma concentrations fall rapidly initially with a distribution half-life of 5.9 +/- 6.0 minutes. After the initial rapid fall, plasma concentrations decrease more slowly with a mean disposition half-life of 156 +/- 51 minutes. On the basis of the pharmacokinetic parameters defined, we recommend that the current infusion regimen for ritodrine be changed. The infusion rate of ritodrine should start at 50 micrograms/minute rather than 100 micrograms/minute. The maximal infusion rate of 350 micrograms/minute should be increased and once labor is inhibited, the infusion rate should be reduced. PMID- 2309827 TI - A study of combined continuous ethinyl estradiol and norethindrone acetate for postmenopausal hormone replacement. AB - In a blinded, prospective, dose-response pilot study of continuous estrogen progestin replacement therapy, 77 thin, nonsmoking, white women, who were 12 to 60 months postmenopausal and had normal medical histories, were randomly assigned to receive one of five dose combinations of daily ethinyl estradiol and norethindrone acetate (20 micrograms and 1.0 mg, 10 micrograms and 1.0 mg, 10 micrograms and 0.5 mg, 5 micrograms and 1.0 mg, and 5 micrograms and 0.5 mg) or conjugated estrogens 0.625 mg on days 1 to 25 and medroxyprogesterone acetate 10 mg on days 16 to 25. An additional 10 women meeting the same criteria served as a comparison group by taking calcium only. During 12 months of therapy, continuous users had significantly less vaginal bleeding and spotting than did sequential users. As compared with baseline values, bone metabolism and computerized tomographic measurements of vertebral trabecular bone density at month 12 indicated reduced bone turnover and increased density in hormone users. Endometrial biopsy specimens were negative for hyperplasia and neoplasia. The continuous ethinyl estradiol-norethindrone acetate tablet, even at the lowest doses studied, provided the same salutary effects on bone, endometrium, and postmenopausal symptoms as sequential therapy while minimizing annoying vaginal bleeding and spotting. PMID- 2309828 TI - Conservative management of cervical pregnancy with subsequent fertility. AB - The reported incidence of cervical pregnancies with subsequent fertility is extremely low. We report a case managed conservatively that allowed for future fertility, and ultimately the delivery of a viable infant at term. The conservative management and a review of the literature are discussed. PMID- 2309829 TI - Oligohydramnios in each sac of a triplet gestation caused by Motrin--fulfilling Kock's postulates. AB - A triplet gestation was treated with Motrin for oral tocolysis. A significant reduction of amniotic fluid was observed, but this was corrected by stopping the drug. A cause-and-effect relationship was established by restarting the Motrin and observing the same development of oligohydramnios, which again returned to normal with discontinuation of the drug. PMID- 2309830 TI - Patient-recorded domiciliary fetal monitoring. AB - Domiciliary fetal monitoring via a telephone link has been in clinical use at the Royal Free Hospital for 2 years, during which time 858 traces of 134 patients who were moderately at risk have been transmitted to the hospital. All recognized abnormal heart rate patterns were detected during the study period. In seven patients obstetric intervention took place on the basis of the domiciliary fetal monitoring recording and subsequent hospital monitoring. There were no intrauterine or neonatal deaths, and there was no overall increase in obstetric operative intervention. There appeared to be a significant reduction in the inconvenience suffered by the patient and her family, compared with conventional monitoring. Fetal heart recordings performed solely by the patient were of a high quality and reduced the demand on midwifery resources. To allow this only 3 hours of midwifery time daily was required and no additional demands on obstetric staff were made. It is anticipated that domiciliary fetal monitoring, performed by patients, will become an essential and established service throughout the United Kingdom (and probably Europe) as the principal means of monitoring fetal well being. PMID- 2309831 TI - Epidural analgesia and autonomic hyperreflexia: a case report. AB - Autonomic hyperreflexia is a serious complication for paraplegic patients. A paraplegic woman in early labor presented with autonomic hyperreflexia. After epidural analgesia was established, hyperreflexia resolved. When the analgesic wore off, hyperreflexia returned. Continuous epidural analgesia may be helpful for pregnant women who are susceptible to autonomic hyperreflexia. PMID- 2309832 TI - Spontaneous resolution of Cushing's syndrome after pregnancy. AB - Pregnancy is a rare occurrence in women with Cushing's syndrome. Even more uncommon is the exacerbation of Cushing's syndrome during pregnancy and spontaneous resolution post partum. We report one such case in which biochemical and radiologic findings suggested adrenocorticotropic hormone-dependent disease. PMID- 2309833 TI - Insulin-dependent diabetes mellitus associated with danazol. AB - Insulin-dependent diabetes mellitus developed in a young woman 8 weeks after the initiation of danazol for treatment of pelvic endometriosis. After discontinuation of danazol the diabetes completely resolved. We suspect a possible cause-and-effect relationship, which has not previously been reported in the literature. PMID- 2309834 TI - Perinatal factors associated with the respiratory distress syndrome. AB - Perinatal factors related to the incidence of respiratory distress syndrome were analyzed by the multiple logistic regression statistical method in 263 mothers and their 298 offspring delivered between 24 and 35 weeks' gestation in a 1-year period in a regional referral perinatal center. The risk of respiratory distress syndrome in white infants rose with decreasing gestational age (p less than 0.0001) while prolonged rupture of membranes of greater than 24 hours in the absence of maternal infection (28% of cases) was highly protective (p less than 0.0001). Compared with vaginal delivery, cesarean delivery without labor increased the risk of respiratory distress syndrome (p = 0.03). The administration of tocolytic drugs was unrelated to the incidence of respiratory distress syndrome, but corticosteroid therapy given at least 72 hours before delivery was protective (p = 0.03). Male and female infants were equally at risk for respiratory distress syndrome as were black and white infants, but other races had a lower incidence (p = 0.004). Infants with respiratory distress syndrome were on mechanical ventilators longer than those with other respiratory illnesses. PMID- 2309835 TI - The effect of disopyramide on uterine contractions during pregnancy. AB - To evaluate the effect of disopyramide on uterine contractions during pregnancy, the drug was given for 48 hours to 10 women with indications for labor induction. Placebo was given to 10 other women with the same indications for induction. During the study period, regular uterine contractions occurred in 10 women in the study group, as compared with none in the control group (p less than 0.0001). Eight women in the study group were delivered of infants within 48 hours, as compared with none in the control group (p less than 0.0001). The mean time until the appearance of regular uterine contractions in the study group (4.15 +/- 1.76 hours) was significantly shorter (p less than 0.001) than that in the control group (56.13 +/- 5.28 hours). Patients who were not delivered of infants within 48 hours received other medications (prostaglandin E2, oxytocin). The mean maternal blood level of disopyramide at the time of appearance of uterine contractions was 1.52 +/- 0.9 mg/ml. The mean maternal level at delivery was 0.93 +/- 0.43 mg/ml and the cord blood level at the time of delivery was 0.33 mg/ml (cord blood/maternal level ratio = 0.36, r = 0.73, p less than 0.05). These results indicate that disopyramide should not be used in pregnancy for antiarrhythmic purposes because it may induce uterine contractions and delivery. PMID- 2309836 TI - Macrosomia: influence of maternal overweight among a low-income population. AB - Macrosomia (birth weight greater than 4000 gm) is associated with a wide variety of adverse intrapartum and perinatal outcomes. To evaluate the effect of pregravid obesity on infant birth weight, we examined data from a low-income population of women (n = 127,879). The population was divided into five groups on the basis of pregravid body mass index (weight/height) designated by the National Health and Nutrition Examination Survey II reference population (less than 25th percentile, 25th to less than 75th percentile, 75th to less than 85th percentile, 85th to less than 95th percentile, and greater than or equal to 95th percentile). The prevalence of infant macrosomia ranged from 5% for the lowest group to 17% for the highest group. With the use of the second group (25th to less than 75th percentile) as a reference, odds ratios (adjusted for maternal age, smoking status, race, height, parity, gestational age, and infant sex) for macrosomia for the five sequential weight groups were 0.6, 1.0, 1.3, 1.6 and 2.2. We conclude that pregravid overweight had a significant independent effect on birth weight outcome. PMID- 2309837 TI - Cytogenetic results of chorionic villus sampling: high success rate and diagnostic accuracy in the United States collaborative study. AB - Cytogenetic results of first-trimester chorionic villus sampling are reported from seven U.S. medical centers. For 6033 patients who had a successful chorionic villus sampling procedure, the rate for obtaining a cytogenetic diagnosis was 99.6% with the direct method, long-term culture, or both. There were no incorrect sex predictions and no diagnostic errors involving trisomies 21, 18, or 13, sex chromosome aneuploidies, or structural abnormalities. There were no cases of normal cytogenetic diagnosis followed by birth of a cytogenetically abnormal infant. Three cases of unusual aneuploidies (tetraploidy, trisomy 16, and trisomy 22) detected by the direct method only were not confirmed by cytogenetic follow up. Mosaic cytogenetic abnormalities were observed in 0.83% of all cases in which chorionic villus sampling was done but were confirmed by amniocentesis or in fetal tissues in only 7 of 30 cases (23.3%). Maternal cell contamination occurred in 1.9% of long-term cultures, although this did not present any cytogenetic diagnostic difficulties. Overall, a very high degree of laboratory success and diagnostic accuracy was observed with either cytogenetic method, although fewer predictive errors were observed with the long-term culture method and none were observed when both methods were used. PMID- 2309838 TI - Orosomucoid in human pregnancy serum diminishes bioavailability of the progesterone antagonist RU 486 in rats. AB - Bioavailability of the progesterone antagonist RU 486 was examined in vivo by measurement of first-pass uptake by hepatic and uterine tissues in rats. Presence of human pregnancy serum or alpha 1-acid glycoprotein (orosomucoid) in injection vehicles diminished uptake of this steroid, which suggests limited bioavailability. These data indicate that elevated human serum orosomucoid levels may account for some failures of RU 486 in early pregnancy termination. PMID- 2309839 TI - Detection of platelet-activating factor in amniotic fluid of complicated pregnancies. AB - The ether phospholipid PAF (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was originally described as a potent bioactive lipid associated with inflammatory responses. More recently, we have suggested a functional role for PAF in fetal lung maturation and the initiation of parturition. Previously, PAF was detected in the amniotic fluid of women at term during labor. A significant proportion of this PAF was associated with a lamellar body-enriched fraction. In addition, the PAF concentration was elevated in fetal rabbit lung during the latter stages of gestation and in human fetal lung in organ culture. It was therefore concluded that the PAF present in amniotic fluid during labor was, in part, of fetal lung origin. In the reported study, amniotic fluid samples were obtained from a group of patients with uncomplicated pregnancies at term "not in labor" and "in labor" and a group with complicated pregnancies. We found an eightfold greater concentration of PAF in amniotic fluid obtained from the "term, in labor" samples compared with that of the "term, not in labor" samples (40 vs. 312 fmol/ml). A twentyfold elevation in PAF (838 fmol/ml) was evident in the amniotic fluid of patients incurring "preterm labor" with an average gestational age of 32 weeks compared with the "term, not in labor" group. PAF concentrations also were elevated to 756 fmol/ml amniotic fluid in a group of patients with an average gestational age of 31.5 weeks who had premature rupture of membranes. We have previously suggested that a second autacoid, PAF, in addition to eicosanoids, may function in the initiation of parturition at term in uncomplicated pregnancies. On the basis of our findings of a severalfold increase in the PAF concentration in amniotic fluid from complicated pregnancies, it is suggested that this potent activator of myometrial contraction, together with the eicosanoids, may be a contributing factor associated with premature labor. PMID- 2309840 TI - Pregnancy increases cardiovascular toxicity to cocaine. AB - The effects of intravenous cocaine on heart rate and blood pressure were studied in pregnant and oophorectomized nonpregnant ewes. In response to intravenous cocaine doses of 1.0 and 2.0 mg/kg, both pregnant and nonpregnant ewes demonstrated dose-dependent increases in systolic, diastolic, mean arterial, and pulse pressures with return to baseline by 30 to 60 minutes after cocaine administration. However, at both doses (1.0 and 2.0 mg/kg) pregnant ewes demonstrated greater increases in mean arterial pressure (+29.6%, +48.7%) than nonpregnant ewes (+15.6%, +27.7%) during the first 5 minutes after cocaine administration. Thereafter the responses were similar. Thus pregnancy increases the cardiovascular toxicity to cocaine. PMID- 2309841 TI - Placental transfer of indomethacin in the human pregnancy. AB - Little is known about the placental transfer of indomethacin in the human pregnancy. Twenty-six pregnant patients (gestational age, 29.4 +/- 0.5 weeks) were given a 50 mg oral dose of indomethacin 6.08 +/- 0.07 hours before 42 cordocenteses undertaken for standard indications. Maternal serum, fetal serum, and amniotic fluid levels were measured at the time of each procedure. Maternal indomethacin levels were not significantly different from corresponding fetal levels (218 +/- 21 vs 219 +/- 13 ng/ml). The maternal/fetal serum ratio (0.97 +/- 0.07) was not found to vary with gestational age (R = -0.07, p = 0.66). Fetal serum levels were significantly higher than corresponding amniotic fluid levels (219 +/- 16 vs. 21 +/- 2 ng/ml; p less than 0.001). The fetal/amniotic fluid ratio (10.0 +/- 1.2) did not vary with gestational age (R = 0.33, p = 0.11). Indomethacin crosses the human placenta easily throughout gestation; only small amounts of the unchanged drug are found in the amniotic fluid. PMID- 2309842 TI - Transcapillary fluid dynamics during ovarian stimulation for in vitro fertilization. AB - Transcapillary fluid dynamics were studied in 10 women during ovarian stimulation for in vitro fertilization. The examinations were done on the first day of stimulation (day 3 of the menstrual cycle, mean serum estradiol concentration 0.2 nmol/L), and the day before oocyte aspiration (day 10 to 12, mean serum estradiol concentration 6.8 nmol/L). Interstitial colloid osmotic pressure was measured on the thorax at heart level by the "wick" method, and interstitial hydrostatic pressure by the "wick-in-needle" method. Plasma colloid osmotic pressure decreased (mean, 2.0 mm Hg; p less than 0.002) and interstitial colloid osmotic pressure increased (mean, 1.0 mm Hg; p less than 0.02) during hormonal stimulation. This implies a reduced transcapillary colloid osmotic gradient (plasma colloid osmotic pressure--interstitial colloid osmotic pressure), probably because of increased capillary permeability to plasma proteins. Hemoglobin and hematocrit were significantly reduced, and body weight and foot volume significantly increased. These results demonstrate that during ovarian stimulation there are both water retention and augmented filtration of fluid from the vascular to the interstitial compartment. This may be of significance for the pathophysiologic condition in the ovarian hyperstimulation syndrome. PMID- 2309843 TI - Nuchal muscle activity at different levels of hypoxemia in fetal sheep. AB - The effects of hypoxemia on nuchal muscle activity, a parameter of gross body movements, were studied during 12 experiments in five chronically instrumented fetal lambs. Hypoxemia was accomplished by tracheal infusion of nitrogen and did not result in significant changes in fetal arterial pH and PCO2. Fetal arterial blood gases and pH were continuously measured with an extracorporeal flow-through cuvette. Nuchal muscle activity was measured by electromyography and was expressed as the percentage of time spent moving. A decrease in fetal arterial oxygen saturation to three fourths of the initial value for 2 hours was not associated with significant changes in nuchal muscle activity. When fetal arterial oxygen saturation was further reduced for 2 hours to one half, fetal nuchal muscle activity fell significantly from 34.6% +/- 10.5% during normoxemia to 20.9% +/- 13.9% during hypoxemia. However, the most pronounced changes in fetal nuchal muscle activity occurred in the first 15 minutes after the changes in arterial oxygen saturation. A considerable transient increase in nuchal muscle activity was observed during the first 15 minutes after recovery from hypoxemia. During hypoxemia there was a relative predominance of short-lasting (less than 3 minute) movements. PMID- 2309844 TI - Etiology and epidemiology of endometriosis. AB - The true prevalence of endometriosis remains undetermined because diagnostic laparoscopy cannot be performed on large, random, population-based samples of women. However, available evidence suggests that the disease occurs in approximately 1% to 7% of women in the United States. The cause of endometriosis is though to be associated with mechanical factors (such as retrograde menstrual flow) or estrogen production. Recent research also has suggested that regular exercise may help to protect against the disease by decreasing the rate of estrogen production. PMID- 2309845 TI - Calculation of fetoplacental volume. PMID- 2309846 TI - Is sampling technique beneficial to fetus? PMID- 2309847 TI - Evaluation of hysteroscopic management of the septate uterus. PMID- 2309848 TI - Need for plasma volume estimation. PMID- 2309849 TI - Pulmonary artery catheterization in severe preeclampsia. PMID- 2309850 TI - Caution regarding fetal acoustic stimulation in oligohydramnios. PMID- 2309851 TI - A nested case-control study of oxytocin and sudden infant death syndrome. PMID- 2309852 TI - Effects of relaxin on calcium concentrations. PMID- 2309853 TI - Cesarean salpingectomy rare but not first. PMID- 2309854 TI - Use of digoxin in pregnancy. PMID- 2309855 TI - Feedback mechanism of human chorionic gonadotropin secretion. PMID- 2309856 TI - Presumed small choroidal melanomas with serous macular detachments with and without surface laser photocoagulation treatment. AB - We reviewed the records of 22 patients (22 eyes) who had presumed small choroidal melanomas associated with a serous macular detachment. In 13 eyes, the tumor surface was treated with laser photocoagulation to reattach the retina and improve vision. After photocoagulation, the retina reattached in 11 eyes (85%), and the visual acuity improved in eight eyes (62%), returning to 20/25 or better in six eyes (46%). Twelve of the tumors (92%) that received surface photocoagulation grew after treatment. Seven of these tumors (54%) developed a collar-button configuration and showed evidence of basal expansion. Of the nine tumors that did not receive surface photocoagulation, seven (78%) eventually grew, but none developed a collar-button configuration. Surface photocoagulation applied to a growing melanoma appears to increase the likelihood of tumor extension through Bruch's membrane in a collar-button configuration. The impact of such growth on tumor metastasis is unknown. PMID- 2309857 TI - Age-related macular changes in humans over 90 years old. AB - The macula lutea of 23 donors aged 90 to 101 years were examined by light and electron microscopy and compared to maculas from a 49- to 68-year-old age group. The number of foveal photoreceptors and retinal pigment epithelial cells, the presence of macular pigment, and lipofuscin fluorescence were assessed. Pathologic characteristics typical of age-related macular degeneration occurred in nine of the 90- to 101-year-old group with changes ranging from early neovascularization to fully developed disciform scars, geographic atrophy, and macular holes. Several retinas had pigment epithelial and photoreceptor cell numbers equal to those of the younger group, but most showed cell loss. Thickened, debris-filled Bruch's membrane and choriocapillary atrophy, although common, were not an invariable accompaniment to old age. Clinicians should advise elderly patients that their chances of maintaining macular structure, and hopefully function, are better than 50%. PMID- 2309858 TI - The pattern electroretinogram in diabetes. AB - In 27 normal subjects and 64 insulin-dependent diabetic patients, we evaluated the pattern electroretinogram, which may reflect the neural activity of the spatially sensitive retinal ganglion cells. The amplitude of the pattern electroretinogram was reduced in diabetic patients who had no observable retinal changes. The amplitude was further reduced with increasing retinopathy. The pattern electroretinogram amplitude change was a more sensitive indicator of retinal change among the diabetic subpopulations than the statistically significant changes in latency. A significant correlation between pattern electroretinogram amplitude and the duration of diabetes were found in diabetic patients with either no observable retinopathy or minimal background retinopathy. The pattern electroretinogram may be useful as a quantitative, dependent variable to establish and monitor short-term metabolic and physiologic changes in diabetic patients. PMID- 2309859 TI - Twin vessels in familial retinal cavernous hemangioma. AB - We investigated the presence of twin vessels in two patients and in four of their relatives at risk from one family with autosomal-dominant hereditary cavernous hemangioma of the retina associated with central nervous system involvement. Twin vessels were detected in four of the six patients examined. The proband had bilateral retinal vascular hamartomas with central nervous system involvement but no twin vessels. The proband's mother had vascular hamartomas of the retina and brain with twin vessels. In the other three family members, twin vessels were associated either with retinal cavernous hemangiomas (one patient) or with normal fundi (two patients). Because twin vessels may be an ocular manifestation of von Hippel-Lindau disease, their presence in one of our two patients and in the otherwise healthy three family members suggests that twin vessels may be associated with different retinal vascular hamartomas, including capillary and cavernous hemangiomas. PMID- 2309860 TI - Helicoid peripapillary chorioretinal degeneration. AB - Study of a father and son who had helicoid peripapillary chorioretinal degeneration suggests that a progressive tearing and retraction of the retinal pigment epithelium or of Bruch's membrane around the optic disk may be involved in the disorder's pathogenesis. We presume that this tearing results primarily from dysplastic abnormalities of the retinal pigment epithelium that surrounds the optic disk. The dystrophic lesions progress slowly and may affect the macula and even the peripheral retina. PMID- 2309861 TI - Posterior vitreous cyst. AB - We observed two patients who had unilateral posterior vitreous cysts; one patient had been observed for 17 years. Both patients were young females who reported transient, infrequent obscurations of vision that were not disabling. One involved eye was emmetropic, and the other was highly myopic. No other ocular abnormalities were present. In the patient observed for 17 years, the physical characteristics of the posterior vitreous cyst remained unchanged. With this stable clinical course, posterior vitreous cyst that does not visually disable the patient may be managed by periodic observation. PMID- 2309862 TI - Anatomy of arteriovenous crossings in branch retinal vein occlusion. AB - We studied the photographic records of 292 eyes, including 103 eyes with branch retinal vein occlusion, 90 fellow eyes, and 99 control eyes without branch retinal vein occlusion. All arteriovenous crossings within three disk diameters of the optic disk, including the crossings at the sites of branch retinal vein occlusions, were studied. The relative positions of the crossing artery and vein could be determined at 1,939 crossings in all eyes. Crossings at which a vein crossed over an artery were a common finding (22.3% to 33.0% of crossings), but were rare at the crossings where branch retinal vein occlusions were found (2.4%). A greater proportion of arterial overcrossings was found in eyes with branch retinal vein occlusions (77.7%) compared to fellow eyes (70.6%) or control eyes (67.0%). Our data indicate that arterial overcrossings are at relatively higher risk of branch retinal vein occlusion than venous overcrossings, and that the risk of branch vein occlusion in an eye is proportional to the number of arterial overcrossings in the eye. PMID- 2309863 TI - Glaucoma in oculo-dento-osseous dysplasia. AB - Two patients with oculo-dento-osseous dysplasia developed glaucoma in infancy or early childhood. Aggressive surgical management resulted in the preservation of vision in both patients in at least one eye. A review of published reports disclosed that glaucoma in oculo-dento-osseous dysplasia develops at different ages and is possibly secondary to a variety of mechanisms. Glaucoma is the main cause of visual loss in this syndrome, for which patients otherwise have a good prognosis for life and intellect. Early screening for glaucoma in oculo-dento osseous dysplasia is mandatory, especially when there are symptoms that suggest high intraocular pressure. PMID- 2309864 TI - Blepharoptosis repair by fascia lata suspension with direct tarsal and frontalis fixation. AB - Nine patients with blepharoptosis and no levator palpebrae superioris muscle function were treated by fixating irradiated fascia lata to the tarsus and frontalis muscles under direct visualization. No recurrences were noted on follow up, which ranged from four to 24 months. There were no postoperative infections or granuloma reactions. Cosmetically, the height, contour, and symmetry of the eyelid margin and eyelid crease were predictable and satisfactory. This modified method of frontalis suspension may provide a more predictable and cosmetically pleasing result in the treatment of blepharoptosis when minimal or no levator muscle function is present. PMID- 2309865 TI - A gas-permeable scleral contact lens for visual rehabilitation. AB - We evaluated the use of a highly gas-permeable, fluid-filled scleral lens for patients with diseased corneas for whom conventional contact lens strategies failed. Fifteen patients were successfully fit with individually fabricated scleral lenses. Significant corneal hypoxia, which limited the use of previous polymethylmethacrylate scleral lenses, was not encountered. Preliminary results suggest that a gas-permeable scleral lens may offer therapeutic as well as visual benefit to some patients with severe corneal disease. PMID- 2309866 TI - Recurrence of posterior polymorphous corneal dystrophy after penetrating keratoplasty. AB - Recurrence of a corneal dystrophy after keratoplasty can occur in multiple dystrophies, including macular, granular, and lattice dystrophies. We treated two unrelated patients who had documented posterior polymorphous dystrophy and who, in previously clear grafts, developed haziness in the zone of Descemet's membrane, which led to graft failure. Histologic examination of the keratoplasty specimen showed changes typical of posterior polymorphous dystrophy. PMID- 2309868 TI - Competition and ophthalmology. PMID- 2309867 TI - Listeria monocytogenes keratitis. AB - We treated a farmer who had Listeria monocytogenes bacterial keratitis. Therapy with topical antibiotics was unsuccessful; it was necessary to treat the patient with topical and systemic penicillin and gentamicin. To elucidate the pathogenesis of this infection, we developed a rabbit model. Using the patient's strain of L. monocytogenes, we determined that the severity of the rabbit infection was dose-related. If we used an inoculum of more than 10(7) organisms, many of the features of the human Listeria keratitis were mimicked. We also found that treatment with either penicillin or gentamicin did not control the infection as well as using both antibiotics simultaneously, a combination which resulted in relatively rapid resolution of infection and no corneal scarring. The human and animal data indicate that L. monocytogenes can be a virulent corneal pathogen. Listeria corneal infections must be treated aggressively with both penicillin and gentamicin to prevent permanent visual loss. PMID- 2309870 TI - Acquired Brown's syndrome after peribulbar anesthesia. PMID- 2309869 TI - Combined superior oblique paresis and Brown's syndrome after blepharoplasty. PMID- 2309871 TI - Capnocytophaga keratitis associated with poor dentition and human immunodeficiency virus infection. PMID- 2309872 TI - Retinoblastoma associated with holoprosencephaly. PMID- 2309873 TI - Floppy eyelid syndrome in a child. PMID- 2309874 TI - Presumed sarcoid choroidopathy mimicking birdshot retinochoroidopathy. PMID- 2309875 TI - Shadow- and reflex-free use of combined fiberoptic manipulators and illuminators in vitreous surgery. PMID- 2309876 TI - A new instrument for ab interno drainage of subretinal fluid. PMID- 2309877 TI - Glaucomalike disks without increased intraocular pressure or visual field loss. PMID- 2309878 TI - Automated perimetry, tonometry, and questionnaire in glaucoma screening. PMID- 2309879 TI - Collaborative relationships: opportunities for occupational therapy in the 1990s and beyond. PMID- 2309880 TI - Evaluating level I fieldwork students: a job model. AB - This article describes how a job model, a behavioral engineering concept used to improve employee performance, was developed to evaluate the clinical performance of occupational therapy students in Level I fieldwork. The job model emphasizes accomplishments and provides immediate feedback on specific skills needed for the successful completion of Level I fieldwork. In a pilot study of 137 students from the Occupational Therapy Teaching Clinic at Western Michigan University, 68 of the students were evaluated with the job model and 69 were evaluated with Western Michigan University's traditional Level I fieldwork evaluation. The results showed that the job model provided a method by which to identify standard values for measuring accomplishments in Level I fieldwork. PMID- 2309881 TI - Occupational therapy intervention with an adolescent with brain injury and behavioral disorders. PMID- 2309882 TI - Employment of occupational therapists in nontraditional settings. AB - From my personal experience as a therapist employed in a nontraditional setting, I have identified the skills and abilities of experienced occupational therapists that are germane to work in nontraditional settings or beyond the clinic walls. Our profession can benefit from therapists working in nontraditional settings by gaining recognition and influencing decision makers in ways that will benefit the clientele that occupational therapists serve. PMID- 2309883 TI - Can we delimit the discipline of occupational therapy? PMID- 2309884 TI - Addition to home health care role. PMID- 2309885 TI - Abstracts of symposia and other special sessions to be presented at the fifty ninth annual meeting of the American Association of Physical Anthropologists. Miami, Florida, April 3-7, 1990. PMID- 2309886 TI - Xanthine oxidase: evidence against a causative role in renal reperfusion injury. AB - The conversion rates of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) were compared with the time course of in vivo lipid peroxidation (LPO) in an ischemia-reperfusion model of acute renal failure in the rat. LPO, measured as the renal release of malondialdehyde (MDA), was found to be markedly elevated only during the first 5 min of blood reflow following a 45-min interval of ischemia (arteriovenous MDA difference -277.3 +/- 53.5 vs. 3.7 +/- 5.7 nmol/l in controls, n = 14). After 30 min of reperfusion, arteriovenous MDA differences nearly reached control values (9.7 +/- 31.8 nmol/l, n = 7). In contrast to enhanced LPO, no significant conversion of XDH to XO was found (XO activity in controls: 23 +/- 1% of XO plus XDH activity vs. 26 +/- 3% after 45 min of ischemia, n = 7). Therefore XO-derived superoxide anion radicals cannot be considered causative for LPO in the reperfusion interval of experimental ischemic acute renal failure. PMID- 2309887 TI - Apical membrane vesicles of ADH-stimulated toad bladder are highly water permeable. AB - Antidiuretic hormone (ADH) stimulation of the toad urinary bladder causes intracellular vesicles called aggrephores to fuse with the apical plasma membrane of granular cells. Aggrephore membranes contain particle aggregates. Particle aggregates are believed to be water channels that cause large increases in the water permeability (PF) of the granular cell apical membrane. Removal of ADH causes the retrieval of particle aggregate-containing apical membrane via endocytosis and a decline in PF. We have previously shown that fluid phase markers are sequestered in these particle aggregate-containing vesicles during retrieval of the apical membrane and that these vesicles can be recovered in cell homogenates. We have now loaded these vesicles with the self-quenching fluorophore carboxyfluorescein (CF) to measure and compare their PF with that of CF-loaded resealed human erythrocyte ghosts. The membranes of these retrieved vesicles have a very high water permeability. The minimum PF of 99% of these vesicles is 4.5 X 10(-2) cm/s. This PF is comparable with that of erythrocyte ghosts (5.4 X 10(-2) cm/s) measured under identical conditions. We conclude that these vesicles are highly permeable to water, and this is consistent with their postulated function of retrieving water channels that have been inserted into the apical membrane in response to ADH. PMID- 2309888 TI - A potassium channel in the apical membrane of rabbit thick ascending limb of Henle's loop. AB - We used the patch-clamp technique to study the activity of single potassium channels in the apical membrane of isolated thick ascending limbs of Henle's loop (TAL) of rabbit kidneys. In cell-attached patches with NaCl Ringer or high-K+ solution in the bath and 140 mM K+ in the pipette, an inwardly rectifying K+ channel was observed with an inward slope conductance of 22.0 +/- 0.5 pS and outward slope conductance of 10.2 +/- 0.3 pS at 22 degrees C (n = 15). The channel was highly selective for K+, with a calculated permeability ratio for K(+)-to-Na+ of 20:1 (n = 4). The open probability (Po) of the channel was 0.89 +/ 0.03 (n = 15) and was not voltage dependent. In inside-out patches with 140 mM K+ in both the bath and the pipette solutions, both Po and conductance of the channel were similar to that in cell-attached patches. Addition of 0.1 mM Ba2+ to the pipette solution reduced Po of the channel in a voltage-dependent manner. Lowering the pH of the bath solution from 7.4 to 6.9 or increasing Ca2+ concentration from 0 to 0.5 mM in inside-out patches did not alter either Po or conductance of the channel. Addition of 2 mM ATP to the bath solution completely inhibited channel activity. This ATP-induced inhibition was fully reversible and was found to be dependent on the ratio of ATP to ADP, since adding 1 mM ADP to the bath solution relieved the ATP-induced blockade. The property of this small conductance K+ channel make it a likely candidate for recycling of K+ across the apical membrane of TAL of the rabbit kidney. ATP and ADP are possible intracellular regulators of the channel's activity. PMID- 2309889 TI - Cell swelling increases intracellular free [Ca] in cultured toad bladder cells. AB - We examined the effect of cell swelling on intracellular free calcium concentration ([Ca]i) in cultured toad bladder cells (TB-M) grown as a polarized monolayer on collagen-coated filters. [Ca]i was measured by use of fura-2, fluorescence microscopy, and simple video imaging. In preliminary experiments we determined that reducing ionic strength by 15% had no effect on the Kd of fura-2, indicating that the dye could be used to examine the effects of cell swelling on [Ca]i. Reducing the osmolality of the serosal bathing medium by 15% caused [Ca]i to increase within 10 s from 97 +/- 9 to 354 +/- 88 nM (n = 5). By 2 min [Ca]i had declined to 163 +/- 22 nM. The increase in [Ca]i was not caused by a fall in Na concentration ([Na]) because isosmotic reduction of serosal [Na] did not result in an increase in [Ca]i. The swelling-induced increase in [Ca]i could be abolished by lowering serosal [Ca] to 200 nM and by addition of lanthanum. The calcium-channel blockers nitrendipine and verapamil also inhibited the swelling induced increase in [Ca]i, although to different degrees. These experiments demonstrate that swelling of cultured toad bladder cells results in a significant increase in [Ca]i by enhancing the rate of calcium entry across the basolateral membrane, possibly through a calcium channel. PMID- 2309890 TI - D-penicillamine and the transport of L-cystine by rat and human renal cortical brush-border membrane vesicles. AB - Brush-border membrane vesicles (BBMV) were prepared from rat and human renal cortical tissue by magnesium aggregation and differential centrifugation, and the uptake of L-cystine, L-cysteine, and L-cysteine-D-penicillamine were assessed by a rapid-filtration technique. L-Cystine uptake was relatively sodium independent and associated with membrane binding. Sodium-stimulated uptake was sensitive to a cation but not anion diffusion potential. Both sodium-independent and sodium stimulated uptake rates were inhibited by the cationic L-amino acids and by some neutral L-amino acids. The uptake rates of L-cysteine and L-cysteine-D penicillamine were more sodium dependent, and sodium-stimulated uptake rates were more sensitive to cation and anion diffusion potentials. Neither the sodium independent nor the sodium-stimulated uptake rates of L-cysteine or L-cysteine-D penicillamine were inhibited by the cationic L-amino acids. L-Cysteine-D penicillamine showed relatively little membrane binding. It is concluded that L cystine is transported into renal cortical BBMV by pathways distinct from those concerned with the transport of L-cysteine and L-cysteine-D-penicillamine, and it is postulated that these differences may account for some of the effects of D penicillamine in cystinuria. PMID- 2309891 TI - Influence of acute hyponatremia on renal ammoniagenesis in dogs with chronic metabolic acidosis. AB - The purpose of this study was to determine how acute hyponatremia might augment the excretion of ammonium in dogs with chronic metabolic acidosis. The excretion of ammonium was higher during hyponatremia because the proportion of ammonium produced that was excreted in the urine increased from 66% in controls to 77%. Effects on the production of ammonium are more complex. The rate of renal ammoniagenesis was not increased during hyponatremia in absolute terms nor when expressed per millimole of oxygen consumption. In contrast, this rate was somewhat higher during hyponatremia if expressed per millimole of sodium reabsorbed (9.8 vs. 10.3 mumol). The rate of oxygen consumption by the kidney did not fall, as anticipated, during hyponatremia; when this rate was expressed per millimole of sodium reabsorbed it rose from 46 to 55 mumol. There was no significant change in the rate of extraction of glutamine by the kidney, but there was a significant decrease in the rate of release of alanine during hyponatremia. Hence there appears to be more oxidation (yielding more ammonium) and less transamination of glutamine. We conclude that the renal events which led to a higher rate of excretion of ammonium during hyponatremia were a larger than expected rate of ammonium production owing to a greater rate of oxygen consumption together with lesser rate of transamination of the glutamine extracted by the kidney. In addition, more of the ammonium produced was transferred to the urine. PMID- 2309892 TI - Membrane crosstalk in the mammalian proximal tubule during alterations in transepithelial sodium transport. AB - The present paper examines the effects of reduced transepithelial Na transport (JNa) on membrane electrophysiological parameters in proximal convoluted tubules and the possible role of cytosolic calcium concentration ([Ca]i) in the regulation of basolateral membrane K conductance (GK). When JNa was reduced by elimination of glucose and alanine and replacement of 100 mM sodium with N-methyl D-glucamine from the luminal perfusate, basolateral membrane potential (VBL) hyperpolarized transiently by 12.6 mV and the ratio of apical to basolateral membrane resistance (RA/RBL) doubled. The apparent transference number for K at the basolateral membrane (GK/Gcell) decreased from 0.13 to 0.08 in the first 4 min following reductions in JNa. The elimination of Na-alanine and Na-glucose cotransport was responsible for the initial hyperpolarization and increase in RA/RBL, whereas the resultant decrease in the cellular concentrations of glucose and alanine, together with the reductions in GK, could elicit the secondary VBL depolarization. Measurement of [Ca]i with the fluorescent probe fura-2 during reductions in JNa revealed that [Ca]i increased by an average of 12%, a value very similar to the average reduction in cellular volume (13%) measured using morphometric techniques. The observation that [Ca]i increased while GK was decreasing is inconsistent with the effect of [Ca]i on putative basolateral Ca activated K channel. We believe that [Ca]i changes passively (at least in the first few minutes) in response to a decrease in cell volume occurring as a consequence of reductions in JNa and that some as yet unidentified volume sensitive mechanism is responsible for the regulation of GK. PMID- 2309893 TI - Sympathetic modulation of renal autoregulation by carotid occlusion in conscious dogs. AB - The effects of a moderate reflex activation of the sympathetic nervous system on renal blood flow (RBF) and glomerular filtration rate (GFR) were studied in 29 experiments on seven conscious foxhounds. Autoregulation parameters were derived by a stepwise reduction of renal artery pressure of 10-mmHg decrements. An occlusion of both common carotid arteries (CCO) was used as a moderate sympathetic stimulus. This procedure did not influence the basal levels of RBF and GFR. However, the lower limits of autoregulation were considerably shifted (RBF, control 63 +/- 3 mmHg vs. CCO 91 +/- 8 mmHg, P less than 0.01; GFR, control 77 +/- 5 mmHg vs. CCO 102 +/- 5 mmHg, P less than 0.01). CCO also affected the rate by which RBF and GFR decreased below the autoregulatory range (subautoregulatory function: RBF, control y = 0.056x - 1.4 vs. CCO y = 0.037x - 0.9 ml.mmHg-1.g-1, P less than 0.05; GFR, control y = 0.0089x - 0.4 vs. CCO y = 0.0054x - 0.28 ml.mmHg-1.g-1, P less than 0.05). An alpha-blockade via intrarenal prazosin infusions markedly inhibited these effects of CCO. These findings demonstrate the failure of autoregulation below 102 mmHg for GFR and 91 mmHg for RBF during sympathetic activation, and they may be of clinical importance for situations that are characterized by a high sympathetic tone. PMID- 2309894 TI - Morphological and functional comparisons of normal and hypertrophied kidneys of adult domestic fowl (Gallus gallus). AB - Similar to mammals, kidneys of domestic fowl undergo compensatory hypertrophy after loss of functional renal mass. Because this species continues to develop new nephrons for up to 12-wk posthatch, renal hyperplasia might play a significant role in compensatory growth. Either transient or permanent loss of approximately 60% of the right kidney was produced in 2- to 3-wk-old roosters by simple ureteral transection or by removing a 1-mm segment of ureter at the level of the ischiadic artery, respectively. In the latter (experimental) group, right anterior and medial divisions atrophied leaving only the posterior division intact. Spontaneous reanastomosis occurred in the former (reconnected) group, and all three divisions were present at death. Control birds were untouched as were the left kidneys of experimental and reconnected birds. At 40-50 wk, renal function was measured separately in right and left kidneys of all groups during five different infusion protocols. Compared with control kidneys, experimental kidneys had a 50-60% weight gain, and their glomerular size distribution profile was shifted to the right (larger glomeruli). Reconnected kidneys were not hypertrophied, and their profile was shifted to the left (smaller glomeruli). Neither group had significant formation of new nephrons. Once variations in kidney weight were taken into account, there were no differences between hypertrophied (experimental) and control kidneys in urine flow rate (UFR), glomerular filtration rate (GFR), paraaminohippuric acid (PAH) clearance, UFR/GFR, urine osmolality, urine/plasma osmolality, osmolal clearance, free water clearance, Na and K load, absolute Na and K excretion, and fractional Na and K excretion except as follows: 1) during infusion of isotonic mannitol-dextrose at 0.1 ml.min-1.kg body wt-1 experimental kidneys had a lower fractional excretion of K than control kidneys, and 2) during brisk osmotic diuresis (isotonic mannitol-dextrose at 0.4 ml.min-1.kg body wt-1) experimental kidneys had higher UFR and free water clearance and lower urine osmolality and urine/plasma osmolality than control kidneys. Reconnected kidneys differed from control kidneys in only 1 of 210 comparisons. Permanent loss of functional renal mass in young birds produces significant compensatory renal hypertrophy that is due to enlargement of existing nephrons rather than formation of new nephrons. Hypertrophied kidneys function like normal kidneys except under conditions of brisk osmotic diuresis. PMID- 2309895 TI - Angiotensin II control of the renal microcirculation in rats with reduced renal mass. AB - It has been suggested that angiotensin II (ANG II) activation after renal ablation contributes to the altered glomerular dynamics and proteinuria that characterizes this model of chronic renal failure. In the present study, male Munich-Wistar rats underwent 75% renal ablation (Nx group). Two weeks later, micropuncture studies were performed in sham-operated rats (sham group) and Nx group rats during intravenous infusion of either a vehicle or two ANG II inhibitors, namely [Sar1, Ala8]ANG II or MK-421 administered at a rate of 0.3 and 1 mg.kg body wt-1.h-1, respectively. Acute ANG II inhibition in sham group had no effect on mean arterial pressure (MAP), glomerular dynamics, or proteinuria. In contrast, in Nx group ANG II inhibition lessened glomerular hypertension (from 64.7 +/- 1.0 to 55.4 +/- 1.7 mmHg, P less than 0.0001) the result of postglomerular vasodilation (P less than 0.01), normalized the glomerular ultrafiltration coefficient (from 0.038 +/- 0.002 to 0.005 +/- 0.002 nl.s-1.mmHg 1, P less than 0.0001), and attenuated proteinuria (from 42.1 +/- 6.5 to 28.1 +/- 5.4 micrograms/min, P less than 0.01). MAP, single-nephron GFR and plasma flow were unaffected. These results suggest that ANG II activity is enhanced in nephrectomy, contributing in a major way to altered glomerular dynamics and proteinuria. PMID- 2309896 TI - Luminal calcium regulates potassium transport by the renal distal tubule. AB - We examined the effect of changes in lumen calcium concentration on net potassium transport by distal tubules in anesthetized rats. Tubules were perfused with a control solution that resembled interstitial fluid but lacked calcium. Experimental solutions were prepared by adding varying amounts of CaCl2 to the control solution to produce solutions with free ionic calcium concentration ([Ca2+]) of 0.2, 0.4, and 0.8 mM. In paired comparisons 0.2 mM Ca2+ did not affect net potassium transport, whereas 0.4 and 0.8 mM Ca2+ each reduced potassium secretion by approximately 30%. Unidirectional potassium fluxes using 86Rb as a tracer for potassium and transepithelial voltage (VTE) were measured to characterize further the effect of calcium on potassium transport. Presence of 0.8 mM Ca2+ in the lumen did not affect unidirectional absorptive potassium flux; therefore, the decrease in net potassium flux was accounted for entirely by a decrease in unidirectional secretory potassium flux. The lumen negative VTE measured in the late distal tubule decreased during perfusion with 0.8 mM Ca2+. These results are consistent with the hypothesis that increases in lumen (extracellular) calcium concentration in the range normally present in the distal tubule reduce net potassium secretion by decreasing the electrochemical gradient for potassium secretion. PMID- 2309897 TI - Synthesis and characterization of a new fluorescent probe for measuring potassium. AB - A new fluorescent probe, 6,7-(4-methyl)coumaro-[2.2.2] cryptand, has been developed for measuring K+. This compound was made by fusing [2.2.2] cryptand with 4-methylcoumarin through 2 ethoxy bridges at the 6 and 7 positions. The probe has a fluorescent excitation peak at 340 nm and an emission peak at 420 nm. In aqueous solutions, increasing the K+ concentration from 0 to 10 mM causes the fluorescence intensity to increase by 143%. The dissociation constant (Kd) for K+ in aqueous solutions is 1.9 mM. In 100% methanol, the Kd for K+ decreases to 0.012 mM, making it possible to measure K+ concentrations in the micromolar range. Na+, tetramethylammonium, NH4+, Ca2+, and Mg2+ have a minimal affect on the fluorescence of the probe in the absence of K+. The coefficient of variation for the measurement of K+ by use of this new dye is less than 1%. In this report, the synthetic procedure is described and the spectral properties of the probe are characterized. Experiments are described demonstrating the use of this probe 1) in measuring K+ in aqueous solutions from 0 to 10 mM and in a microfluorometric assay to measure K+ from 0.0005 to 0.003 mM and 2) in monitoring K+ transport in rabbit proximal tubule brush-border membrane vesicles. PMID- 2309898 TI - Sarcolemmal integrity and metabolic competence of cardiomyocytes under anoxia reoxygenation. AB - In tissue, mechanical cell-to-cell interactions may contribute to cardiomyocyte injury in anoxia-reoxygenation. In the present study, the disturbance of energy metabolism and cell injury were investigated in isolated cardiomyocytes, free of external mechanical constraints. Cardiomyocytes from adult rat, attached to culture dishes, were exposed to 120 min of anoxia and 15 min of reoxygenation in a substrate-free modified Tyrode solution. The energetic state of the cells in anoxia-reoxygenation was characterized by the free-energy change of ATP hydrolysis (delta GATP), amounting to 57 kJ/mol ATP in normoxia. After 120 min of anoxia, all cells were contracted to 65% of their length and delta GATP decreased to 41 kJ/mol. No lactate dehydrogenase was released. Reoxygenation caused a partial oxygen paradox: immediate hypercontracture of the cells, but no release of lactate dehydrogenase. delta GATP recovered to 51 kJ/mol within 15 min. The results demonstrate that anoxic cardiomyocytes can be energy depleted without losing sarcolemmal integrity. They can undergo hypercontracture, elicited by reoxygenation, and yet an almost normal delta GATP can be reestablished. PMID- 2309899 TI - Wavefront myocyte injury and relationship to function in right ventricular ischemia. AB - Past studies of acute canine right ventricular (RV) ischemia have failed to demonstrate early irreversible injury or decreased function. However, the dog frequently has an extensive collateral circulation not found in all humans. The aim of this study was to measure RV global and regional function after right coronary occlusion in 32 closed-chest pigs. RV function was assessed by biplane ventriculography, and myocardial injury was examined by immunohistochemical localization of creatine kinase (CK) and by electron microscopy. Global RV ejection fraction and apical and midventricular regional function declined significantly after 10 min of occlusion. Injury to the myocardium progressed from the endocardium to the epicardium. Significant injury was observed in myocytes of the endocardium, midmyocardium, and epicardium at 10, 30, and 60 min of occlusion, respectively. Regional RV function and the extent of myocardial injury showed a high correlation (r = 0.96, P less than 0.01). The strong CK immunostaining seen in control hearts was diminished in myocytes along the endocardium at 15 min of occlusion. Depletion of immunoreactive CK in myocytes progressed toward the epicardium with longer ischemic times. These findings demonstrate that RV ischemic injury progresses in a wavefront fashion in the pig, which has similar coronary anatomy to humans, and irreversible myocardial injury occurred after 15-30 min of ischemia. PMID- 2309900 TI - Baroreflex attenuates pressor response to graded muscle ischemia in exercising dogs. AB - Graded reductions in hindlimb perfusion in dogs exercising at 2 miles/h (0% grade) elicited reflex pressor responses by what is referred to as the "muscle chemoreflex." To determine the extent to which arterial baroreceptor reflexes oppose the muscle chemoreflex, we elicited pressor responses to muscle ischemia before and after chronic surgical denervation of the arterial baroreceptors. The muscle chemoreflex showed a threshold beyond which systemic pressure rose approximately 3 mmHg for each 1-mmHg decrease in hindlimb perfusion pressure when the arterial baroreceptors were intact. Arterial baroreceptor denervation approximately doubled the pressor responses, i.e., systemic pressure rose by approximately 6 mmHg for each 1-mmHg fall in hindlimb perfusion pressure, without alteration in threshold. We conclude that during mild dynamic exercise, the arterial baroreflexes oppose the pressor response to graded reductions in hindlimb perfusion, reducing it by approximately 50%. When unopposed by the arterial baroreflexes the muscle chemoreflex exhibits a gain (ratio of change in systemic pressure to change in hindlimb perfusion pressure) of approximately -6; thus this reflex can correct by 85% the decrease in muscle perfusion pressure caused by partial vascular occlusion. PMID- 2309902 TI - Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs. AB - We studied the effects of metabolic and respiratory acidosis (pH 7.20) and alkalosis (pH 7.60) on pulmonary vascular tone in 32 pentobarbital-anesthetized dogs ventilated with hyperoxia (inspired oxygen fraction, FIO2 0.40) and with hypoxia (FIO2 0.10). Ventilation, pulmonary capillary wedge pressure (Ppw), and cardiac output (3 l.min-1.m-2) were maintained constant to prevent passive changes in pulmonary arterial pressure (Ppa). Metabolic acidosis and alkalosis were induced with HCl (2 mmol.kg-1.h-1) and NaHCO3-Na2CO3 (5 mmol.kg-1.h-1) infusions, respectively, and respiratory acidosis and alkalosis by modifying the inspiratory CO2 fraction. The hypoxia-induced rise in Ppa-Ppw gradient increased from 5 to 9 mmHg in metabolic acidosis (P less than 0.001), decreased from 6 to 1 mmHg in metabolic alkalosis (P less than 0.001), remained unchanged in respiratory acidosis, and decreased from 5 to 2 mmHg in respiratory alkalosis (P less than 0.001). Linear relationships were found between pH and Ppa-Ppw gradients. These data indicate that in intact anesthetized dogs, metabolic acidosis and alkalosis, respectively, enhance and reverse hypoxic pulmonary vasoconstriction (HPV). Respiratory acidosis did not affect HPV and respiratory alkalosis blunted HPV, which suggests an pH-independent vasodilating effect of CO2. PMID- 2309901 TI - Activity of in vivo canine ventricular neurons. AB - The spontaneous activity of 113 neurons located in the ganglionated plexus in the epicardial fat overlying the cranial portion of the ventral intraventricular groove and the origin of the circumflex coronary artery was recorded in ten anesthetized dogs. Ganglia that contained varying numbers of neurons, some with two or more nucleoli, were subsequently identified anatomically in the vicinity of the recording sites. Spontaneous activity was correlated with the cardiac cycle in 81% and with the respiratory cycle in 17% of the identified neurons. The spontaneous cardiovascular-related activity occurred in relation to specific phases of the cardiac cycle when arterial pressure was between approximately 80 and 175 mmHg. When systolic pressures fell below approximately 80 mmHg or increased above approximately 175 mmHg, neurons displaying cardiovascular-related activity were inactive. The activity of 62% of all identified neurons was altered when discrete regions of the heart or pulmonary tissue were mechanically distorted by gentle touch. In many instances mechanical distortions of tissues were still able to alter neuronal activity following acute decentralization. Single stimuli or trains of stimuli delivered to the vagosympathetic complexes, stellate ganglia, or cardiopulmonary nerves generated bursts of activity in ganglionic neurons. Spontaneous activity occurred whether the ganglia were connected to the central nervous system or acutely decentralized. It is concluded that some neurons located on the canine ventricle display spontaneous activity that is related to cardiovascular or respiratory dynamics. The results also demonstrate that ventricular neurons can be influenced by sympathetic or parasympathetic efferent axons as well as cardiac mechanoreceptors. PMID- 2309903 TI - Vascular washout reduces Ca2+ overload and improves function of reperfused ischemic hearts. AB - Relationships between myocardial Ca2+ uptake, recovery of ventricular function, and restoration of tissue metabolites were determined during 30 min of reperfusion following ischemic and anoxic perfusion with either zero or low coronary flow, zero flow with intermittent perfusion, and low-flow perfusion without substrates. When zero-flow ischemia was maintained for 30 or 40 min, tissue lactate levels increased approximately 100-fold; with reperfusion of these hearts, developed pressure recovered to only 70 and 40% of preischemic function, respectively, and Ca2+ uptake increased by 7- and 15-fold. In contrast, 30 min of low-flow (1 ml/min) anoxic perfusion resulted in accumulation of less lactate (15 fold increase), less reperfusion Ca2+ uptake, and recovery of developed pressure to the preanoxic level. Omission of energy substrates during the low-flow anoxic perfusion caused a reduced recovery of heart rate with lower high-energy phosphate levels and increased Ca2+ uptake, but contractile function recovered to the same extent as in low-flow perfusion with substrate. Even very low flow rates (0.06-0.16 ml/min) of oxygen-deficient perfusate increased high-energy phosphate content and contractile function and decreased Ca2+ uptake. Intermittent perfusion with either oxygenated or anoxic buffer between four 10-min episodes of ischemia reduced lactate accumulation, maintained function, and left Ca2+ uptake essentially unchanged. Recovery of developed pressure during reperfusion was negatively correlated with the amount of lactate that accumulated during ischemia or anoxia and with reperfusion Ca2+ uptake, regardless of the duration or type of ischemia or anoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309904 TI - Effect of human recombinant superoxide dismutase on canine myocardial infarction. AB - To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) "low-dose" h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) "high-dose" h SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion. PMID- 2309905 TI - Relation between left ventricular systolic resistance and contractile rate processes. AB - To test the hypothesis that left ventricular (LV) systolic resistance is determined by the intrinsic rate processes of the contractile system, we studied 40 spontaneously hypertensive male rats (SHR). Thyroid hormone manipulation was used to alter isomyosin composition and consequently the rate processes of the contractile system. Seven groups of rats were studied: control (SHRC, n = 9); propylthiouracil (PTU) treated for 10 days (SHRP-10, n = 5), 20 days (SHRP-20, n = 5), and 30 days (SHRP-30, n = 6); and thyroxine treated for 5 days (SHRT-05, n = 5), 10 days (SHRT-10, n = 5), and 15 days (SHRT-15, n = 5). In situ (n = 40) and isolated (n = 14; 5 SHRP-30, 5 SHRC, and 4 SHRT-15) heart experiments were performed. In comparison to SHRC, we observed the following: 1) LV pump performance was not different in any of the thyroxine-treated groups, whereas with PTU, pump performance was significantly depressed in rats with greater than 80% slow myosin. 2) Normalized LV peak elastance (Emaxn) was significantly increased in the SHRP-30, whereas it was not altered after thyroxine. These observations were further confirmed in the isolated heart on the basis of peak isovolumetric stress-strain relations. 3) Thyroxine increased and PTU decreased theoretical maximum flow (Qmax; a measure of LV resistance); thus an inverse relation between Qmax and percent slow myosin was observed (r2 = 0.86). 4) The time to peak isovolumetric pressure was increased in SHRP-30 and decreased in SHRT-15. The relaxation process was significantly slower for SHRP-30 group and was unchanged for SHRT-15 group. These observations support our hypothesis that LV systolic resistance quantifies an intrinsic rate-dependent property of the myocardium and that isomyosin composition is one of its determinants. In addition, with changes in isomyosin composition toward predominantly slow myosin, the responses in Emaxn and Qmax are discordant, which may be responsible for the preservation of pump performance. This underscores the importance of quantifying both LV systolic resistance and elastance in the assessment of the functional status of the LV as a mechanical pump. PMID- 2309906 TI - Changes in microvascular permeability with acceleration of edema in dog lungs. AB - Elevation of left atrial pressure to 25-40 mmHg causes continuous pulmonary edema formation in dog lungs. However, after 5-120 min, the rate of edema formation often increases (acceleration of edema). Acceleration of edema could be associated with an increase in microvascular membrane permeability because an increase in permeability would cause fluid to filter through the microvascular membrane more rapidly. To test the hypothesis that acceleration is associated with increased permeability, we used the continuous weight-gain technique to estimate the pulmonary microvascular membrane filtration coefficient (Kf) before and after acceleration of edema in 10 dogs. Acceleration occurred 36 +/- 38 (SD) min after elevation of left atrial pressure to 35.2 +/- 5.4 mmHg. Rate of weight gain increased from 0.47 +/- 0.17 g/min before acceleration to 0.88 +/- 0.26 g/min (P less than 0.05) after acceleration of pulmonary edema. Kf was increased from initial values of 0.058 +/- 0.027 to 0.075 +/- 0.029 ml.min-1.mmHg-1 (P less than 0.05) after acceleration. In five additional dogs we cannulated lung lymphatics and determined the lymph to plasma protein concentration ratio (CL/CP) before and after acceleration. CL/CP increased from base-line values of 0.37 +/- 0.07 to 0.44 +/- 0.06 (P less than 0.05) after acceleration. Both the increase in Kf and CL/CP data support the hypothesis that acceleration of edema is due, in part, to a slight increase in microvascular membrane permeability. However, the findings could also have been caused by an increase in interstitial conductance, washout of interstitial proteins, or alveolar flooding. PMID- 2309907 TI - Vasopressin and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs. AB - The interaction between vasopressinergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious hypotensive newborn pig was investigated. Indomethacin treatment (5 mg/kg) of hypotensive piglets caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 52 and 198% 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.58 +/- 0.32 ml.100 g-1.min-1 to 1.01 +/- 0.12 and 0.29 +/- 0.08 ml.100 g-1.min-1 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Treatment with the putative vascular (V1) receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine]arginine vasopressin (MEAVP) had no effect on regional cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or during hemorrhagic hypotension. However, decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were blunted markedly in animals treated with MEAVP. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn pig, as reported previously, and implicate removal of vasopressinergic modulation by prostanoids as a potential mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets. PMID- 2309908 TI - Effects of angiotensin II on blood flow to choroid plexus. AB - The choroid plexus contains receptors for angiotensin II and a very high concentration of angiotensin-converting enzyme. The goal of this study was to test the hypothesis that angiotensin II decreases blood flow to the choroid plexus. In rabbits anesthetized with chloralose, blood flow (microspheres) to the choroid plexus was 438 +/- 46 (mean +/- SE) ml.min-1.100 g-1 under control conditions. Angiotensin II (10, 30, and 100 ng.kg-1.min-1 iv) decreased blood flow to the choroid plexus by 12 +/- 8, 39 +/- 7, and 57 +/- 5%, respectively, with aortic pressure maintained at control levels. Cerebral blood flow was not affected by angiotensin II. Blood flow to the kidney decreased by 15 +/- 7, 30 +/ 3, and 49 +/- 5%, respectively, during infusion of the three doses of angiotensin II. The angiotensin II antagonist saralasin (1 micrograms.kg-1.min-1 iv) did not affect blood flow to the cerebrum or the choroid plexus under control conditions. Saralasin blocked the vasoconstrictor effect of angiotensin II on the choroid plexus and the kidney. Thus circulating angiotensin II has important and parallel effects on blood flow to the choroid plexus and kidney that are mediated by angiotensin II receptors. We speculate that circulating and perhaps locally produced angiotensin II may play an important role in regulation of blood flow to the choroid plexus. PMID- 2309909 TI - Influence of adenosine on left ventricular performance in conscious dogs. AB - Adenosine, a potent vasodilator of both the peripheral and coronary vasculature, is increasingly used to produce controlled hypotension in the clinical and experimental setting. To define the influence of adenosine on left ventricular (LV) performance in conscious closed-chest dogs were studied six chronically instrumented autonomically blocked animals before and after the administration of 0.3, 0.6, and 1.2 microM.kg-1.min-1 infusions of adenosine. Systolic performance was quantified by the end-systolic pressure-volume (Pes-Ves) and stroke work end diastolic volume (SW-EDV) relations. Active diastolic performance was quantified by the time constant of LV relaxation (T), whereas passive diastolic properties were assessed by comparing LV pressures at a common LV volume. Despite a decrease of mean arterial pressure of 51 mmHg, adenosine did not change the slope of the Pes-Ves relation or the end-systolic volume at a pressure of 100 mmHg. The slope of the SW-EDV relation was also unchanged, and its volume axis intercept was slightly reduced. There were no differences in T or in the diastolic pressure at a common LV volume. Thus adenosine appears to have little influence on systolic or diastolic LV performance aside from its marked affect on afterload, indicating it is a useful agent for producing controlled hypotension. PMID- 2309910 TI - Force measurements from voltage-clamped guinea pig ventricular myocytes. AB - We describe the first observations of isolated mammalian guinea pig ventricular myocytes that combine measurements of contractile force with the voltage-clamp method. The myocytes were attached by poly-L-lysine to the beveled ends of a pair of thin glass rods having a compliance of 0.76 m/N. The contractile force of a cell caused a 1- to 3-microm displacement of the rods; the motion of which was converted to an output voltage by phototransistors. By the use of the whole cell patch-clamp technique, the cells were depolarized at 1 Hz with 200-ms-long clamp pulses from -45 to +5 mV (35 degrees C, 3.6 mM CaCl2). Isometric force began after a latency of 7 +/- 2 ms, peaked at 93 +/- 21 ms, and relaxed (90%) at 235 +/- 63 ms. The time course of force was always faster than that of isotonic shortening (time to peak 154 +/- 18 ms). With 400-ms-long depolarizations, a tonic component was recorded as either sustained force or sustained shortening that decayed on repolarization. Substitution of Ca by Sr in the bath increased the inward current through Ca channels but slowed down the time course of force development. The results are consistent with the hypothesis that activator calcium derives mainly from internal stores and that Ca release needs Ca entry through channels. PMID- 2309911 TI - Hepatic microvascular changes associated with development of liver fibrosis and cirrhosis. AB - Quantitative data defining basic microvascular parameters are needed for better understanding of the relationship between liver blood flow and function under normal and pathological conditions. The present study was undertaken to quantitate the following microvascular parameters: flow velocities in sinusoids and terminal hepatic venules; the range of sizes of terminal hepatic vessels; and acinar sizes in both normal rat livers and during the development of liver cirrhosis. Fibrosis and cirrhosis were induced by either weekly administration of carbon tetrachloride (CCl4) or by choline-deficient diet. Microcirculation was observed using intravital epifluorescent video microscopy and recorded on a videotape for subsequent analysis. It was found that even early stages of liver disease, when only mild hepatic fibrosis was present, are associated with profound changes in the hepatic microvasculature. These changes include the appearance of highly fluorescent cells in the liver parenchyma (mainly in the areas where collagen is being deposited), a marked dilatation of the terminal hepatic venules, an increase in hepatic venous outflow, and appearance of sinusoids with very high flow velocities. As fibrosis progresses to cirrhosis, the proportion of these "fast sinusoids" increases from 7% in fibrotic livers to 33% in cirrhotic livers. These results demonstrate the presence of functional intrahepatic shunts in cirrhotic livers and support the hypothesis that hyperdynamic splanchnic circulation may be an important factor in the etiology of portal hypertension in liver disease. PMID- 2309912 TI - Epicardial serotonin receptors in circulatory control in conscious Sprague-Dawley rats. AB - To investigate cardiac chemoreceptors in rats a catheter was chronically implanted into the pericardial sac via the thymus. Intrapericardial (ipc) injection of 200 microliters isotonic saline vehicle did not alter arterial blood pressure, heart rate, right atrial pressure, or respiratory rate. Phenyl biguanide (PBG) and nicotine (NIC) were injected into the pericardial sac. In intact rats anesthetized with methohexital sodium, 90 micrograms PBG ipc decreased blood pressure (BP), heart rate (HR), and renal nerve activity (RNA), whereas 300 micrograms NIC ipc increased BP and decreased HR and RNA. Sinoaortic baroreceptor denervation (SAD) did not affect the responses to PBG and abolished only the HR response to NIC. When vagotomy was added to SAD, all responses to intrapericardial PBG were abolished, but the increase in BP and decrease in RNA resulting from intrapericardial NIC persisted. In SAD rats anesthetized with methohexital, PBG produced dose-dependent decreases in BP and RNA, whereas NIC produced dose-dependent increases in BP and decreases in RNA; the serotonin (5 HT3) antagonist MDL 72222 (80 micrograms ipc) abolished the responses to PBG but not to NIC. MDL 72222 inhibited BP and RNA responses to PBG to a similar extent in conscious and anesthetized SAD rats. Anesthesia attenuated the magnitude and time course of BP and RNA responses to PBG compared with the conscious state. In conclusion, 1) sympathoinhibitory responses to intrapericardial PBG and NIC are mediated by epicardial receptors with different afferent neural pathways, PBG by cardiac vagal afferents and NIC by nonvagal, possibly cardiac sympathetic afferents; 2) PBG exerts its effects via epicardial 5-HT3 receptors; 3) anesthesia attenuates the responses to PBG. PMID- 2309913 TI - Interaction between left ventricular end-diastolic and end-systolic volumes in normal humans. AB - The extent to which the end-systolic volume (ESV) "follows" the end-diastolic volume (EDV) when the latter changes in response to various perturbations is a major determinant of the cardiac ejection fraction (EF) and has not been studied in humans. We measured EDV, ESV, and EF, determined by gated blood pool scans, during a change in posture from the supine to the upright seated position and during graded upright bicycle exercise. The experimental group consisted of 119 healthy individuals (79 males and 40 females) ranging in age from 21 to 81 yr and in physical-conditioning status (75-225 W maximum work load); rigorous screening excluded cardiac disease. Multiple regression analysis showed that the change in ESV (delta ESV) during a postural shift or during graded exercise was highly statistically correlated with the change in EDV (delta EDV) that occurred (r2 ranged from 0.34 to 0.49, correlation is positive) regardless of age, sex, or exercise work load. The correlation of delta ESV with delta EDV observed in this large sample, heterogeneous with respect to age, sex, and physical fitness, was also present in additional 31 subjects who exercised during beta-adrenergic blockade (propranolol 0.15 mg/kg). The delta EF with posture change and exercise in all subjects under all conditions was highly and inversely correlated with the delta ESV (r2 ranged from 0.38 to 0.81). Thus the delta ESV during the circulatory adaptive response to orthostatic and exercise stresses in humans is related to the delta EDV, and this relationship modulates the delta EF in response to these stresses. PMID- 2309914 TI - Ejection- and isovolumic contraction-phase wall thickening in nonischemic myocardium during coronary occlusion. AB - During acute regional ischemia in open-chest anesthetized dogs, contraction is augmented in nonischemic myocardium. The effectiveness of enhanced contraction, however, has been questioned based on recent studies (using midwall segment length measurements) that reported that most of the increase occurred only during the isovolumic contraction phase (ICP) and not the ejection phase (EP) of systole. We evaluated this issue retrospectively using a different means of measuring regional myocardial function, systolic wall thickening (measured with sonomicrometers). In open-chest anesthetized dogs we observed a significant increase in both ICP and EP wall thickening. With circumflex occlusion, ICP and EP thickening each contributed an average of 50% to the augmentation in total thickening. With left anterior descending occlusion, ICP thickening contributed a significantly greater proportion (71%) to the total increase, but the change in EP thickening was also significant (29%). Therefore, in open-chest dogs we observed evidence of intraventricular unloading (in that ICP thickening increased), but we also observed an increase in effective (EP) thickening. In a series of conscious dogs, however, we observed no significant change in total nonischemic thickening after circumflex coronary occlusion. There was a statistically significant increase in the ICP component acutely after coronary occlusion, but its contribution to total wall thickening was small. In a group of dogs studied at intervals for 2 wk after circumflex occlusion, there was no evidence of intraventricular unloading beyond 3-5 days postocclusion. Therefore, we conclude that significant intraventricular unloading is restricted to the acute phases of myocardial infarction, and we suggest that its functional importance is smaller in conscious closed-chest chest dogs than in open-chest dogs. PMID- 2309915 TI - Coronary hyperperfusion and ventricular function in intact and isovolumic pig hearts. AB - This study characterized the effect of coronary hyperperfusion on left ventricular (LV) geometry and myocardial vascular and tissue volumes in intact hearts, and tested the hypothesis that ventricular function is significantly enhanced only under isovolumic conditions. Randomized 10-min trials of coronary perfusion pressures at approximately 100-110, approximately 150-160, and approximately 180-190 mmHg were performed in extracorporeally perfused pig hearts. First, ultrasonic crystals were used to measure LV wall thickness and major and minor epicardial diameters. LV pressures, maximum dP/dt, and myocardial O2 consumption were not significantly different despite increases in the end diastolic and end-systolic wall thickness. There were either no changes or small decreases in epicardial major and minor axis dimensions. Second, intramyocardial small vessel vascular and extracellular volumes were measured using radiolabeled dextran and inulin. There was no significant difference in small vessel plasma volume or extracellular space. Finally, pigs were placed on cardiopulmonary bypass and LV volume was fixed with a ventricular balloon. In this isovolumic preparation, coronary hyperperfusion significantly increased peak LV pressure. We conclude that coronary hyperperfusion in hearts with intact peripheral circulations results in small changes in LV geometry but no physiologically significant changes in LV performance. Only under the rigid conditions of an isovolumic preparation is LV function enhanced, and thus the "garden-hose" effect is a model-dependent phenomenon. PMID- 2309916 TI - Role of blood volume expansion in Dahl rat model of hypertension. AB - Continuous measurement and servo control (SC) of total body weight of unrestrained rats were used to investigate the role of volume expansion in the development of hypertension in Dahl salt-resistant (SR) and Dahl salt-sensitive (SS) rats. A change in sodium intake from 1 to 20 meq/day was associated with an increase in total body weight of 7.2% in both SS and SR rats over 96 h. Plasma sodium (pNa) increased from 145.0 to 147.4 meq/l in both SS (n = 10) and SR (n = 10) rats. Only in the SS rats was the volume expansion associated with an increase in arterial pressure of 27 +/- 3 mmHg. Prevention of the volume expansion by SC blocked the rise in arterial pressure in the SS rats (n = 10) but increased pNa from 143.5 to 152.4 meq/l. Hematocrit fell from 36.6 to 27.5% in both non-SC groups but decreased less in SC groups (35.7 to 32.0%). Plasma volume expansion from 17.6 +/- 0.6 to 25.2 +/- 0.8 ml in non-SC rats was greatly blunted by SC. In non-SC rats, SS (n = 10) and SR (n = 9) rats an increase in salt intake was associated with a rise in cardiac output from 413 +/- 6 to 507 +/- 12 ml.min 1.kg-1 in both groups. These results indicate that fluid retention is required to trigger the rise of pressure in Dahl SS rats. PMID- 2309917 TI - Effects of atherosclerosis on the coronary microcirculation. AB - We tested the hypothesis that atherosclerosis potentiates coronary vasoconstriction to serotonin and ergonovine. Coronary microvascular pressures and diameters were measured in the beating left ventricle in normal and atherosclerotic cynomolgus monkeys. Pressures were measured in arteries (190-350 microns diam) that were distal to atherosclerotic lesions. Microvascular pressure and simultaneous measurements of aortic pressure and myocardial blood flow were used to calculate segmental vascular resistance (large artery resistance and microvascular resistance) during serotonin, phenylephrine, and ergonovine dosages. Aortic pressure was maintained constant during all interventions. Administration of phenylephrine (50 micrograms.kg-1.min-1 iv) produced a similar increase in microvascular resistance from base line (P less than 0.05) in atherosclerotic and normal animals, 26 +/- 5 and 14 +/- 9 mmHg.min.g.ml-1, respectively. Serotonin (50 micrograms/min) did not influence coronary resistance in normal animals but produced a significant increase in both large artery (8 +/- 3 mmHg.min.g.ml-1) and microvascular resistance (21 +/- 6 mmHg.min.g.ml-1) in atherosclerotic animals (P less than 0.05). A higher dose of serotonin (200 micrograms/min) produced a modest increase in large artery resistance from base line in normal animals (3 +/- 1 mmHg.min.g.ml-1) and a greater increase in atherosclerotic animals (9 +/- 4 mmHg.min.g.ml-1) (P less than 0.05 vs. normals). Ergonovine (10 micrograms.kg-1.min-1 iv) elevated microvascular resistance in both normal and atherosclerotic animals (P less than 0.05) but increased large artery resistance only in atherosclerotic animals (10 +/- 4 mmHg.min.g.ml-1) (P less than 0.05). In summary, coronary vasoconstrictor responses to serotonin and ergonovine were potentiated by atherosclerosis. Because augmented constrictor responses to serotonin were observed in both the diseased arteries and the microcirculation of atherosclerotic animals, we speculate that the pathophysiological consequences of atherosclerosis extend into the microcirculation. PMID- 2309918 TI - Spatial distribution of protein in interstitial matrix of rat mesenteric tissue. AB - Interstitial matrix protein has been measured by collecting fluid from implanted capsules and wicks. If the interstitial matrix is well mixed, then these measurements provide an accurate indication of perivascular protein concentration. However, there is increasing evidence suggesting that interstitial protein distribution is nonuniform. To test this hypothesis, a combined light scattering and protein absorbance image of mesenteric tissue in a pentobarbital anesthetized rat was obtained by using an ultraviolet-sensitive television camera to perform videomicrospectrophotometry. In avascular tissue regions protein was organized into periodic nonuniform ridges and valleys. On a smaller scale, the protein along a ridge was organized into clusters. Similar clusters were seen along the wall of small tortuous microvessels and were accompanied by radial gradients in protein distribution. High protein concentration tunnels were occasionally seen extending from a microvessel into the interstitial matrix. A two-way analysis of variance shows that macromolecular spatial distribution is nonuniform (P less than 0.001). Thus the hypothesis that the extracellular matrix is well mixed fails for macromolecules in rat mesenteric loose connective tissue. PMID- 2309919 TI - Simultaneous measurement of Ca2+, contraction, and potential in cardiac myocytes. AB - A system is described that can simultaneously record cytosolic Ca2+ concentration ([Ca2+]i), cell length, and either membrane potential or current in single cardiac myocytes loaded with the fluorescent Ca2+ indicator indo-1. Fluorescence is excited by epi-illumination with 3.8-microsecond flashes of 350 +/- 5 nm light from a xenon arc. Indo-1 fluoresence is measured simultaneously in spectral windows of 391-434 nm and 457-507 nm, and the ratio of indo-1 emission in the two bands is computed as a measure of [Ca2+]i for each flash. With cells loaded with the permeant acetoxymethyl ester of indo-1, quantitation of [Ca2+]i is not precise, owing to subcellular compartmentation of indo-1; however, the instrument would allow full quantitation if indo-1 free acid was introduced by microinjection. Simultaneously, cell length is measured on-line from the bright field image of the cell. Because fluorescence collection is time gated during the brief flash, and red light (650-750 nm) is used for the bright-field image, cell length and [Ca2+]i measurements are obtained simultaneously without cross talk. Membrane potential or current can be recorded simultaneously with indo-1 fluorescence and cell length via standard patch-clamping techniques. PMID- 2309920 TI - Noise reduction in estimating cardiac deformation from marker tracks. AB - Deformation of the cardiac wall is measured by using optical or radiopaque markers attached to the wall. When digitized images are used, the accuracy of the measurement of a marker position is limited by pixel resolution and the size of the marker. The spatial accuracy is improved by singular value decomposition (SVD) filtering. This filtering procedure is based on the assumption that displacements of markers are mutually related because they are embedded in a common continuum. In a computer stimulation with 48 markers in 51 video frames, the accuracy of the measurement of a marker position improved from 0.14 to 0.045 (SD) pixel. In an open-chest animal experiment, with markers on the surface of the heart, the deformation patterns were extracted more clearly using SVD filtering, while mutually related high-frequency components were not suppressed. In a 50-frame sequence of 256 X 256 video images of a 45 mm X 35 mm deforming surface with 50 markers of 8 pixels in diameter, the marker position resolution improves from 0.1 to 0.03 (SD) pixel (6 microns). Strain is determined with an accuracy of 0.002 over a distance of 30 pixels (6 mm). PMID- 2309921 TI - Calcium release from cardiac sarcoplasmic reticulum induced by photorelease of calcium or Ins(1,4,5)P3. AB - The ability of Ca2+ or inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to release Ca2+ from cardiac sarcoplasmic reticulum (SR) was investigated using saponin skinned ventricular trabeculae from rats. To overcome diffusion delays, rapid increases in the concentrations of Ca2+ and Ins(1,4,5)P3 were produced by laser photolysis of "caged Ca2+" (Nitr-5) and "caged Ins(1,4,5)P3". Photolysis of Nitr 5 to produce a small jump in [Ca2+] from pCa 6.8 to 6.4 induced a large and rapid force response (t1/2 = 0.89 s at 12 degrees C); the source of the Ca2+ that activated the myofibrils was judged to be the SR, since it was blocked by 0.1 mM ryanodine or 5 mM caffeine. A smaller, slower, and less consistent release of SR Ca2+ was produced by photorelease of Ins(1,4,5)P3. The results demonstrate that these caged compounds can be used to study excitation-contraction coupling in skinned multicellular preparations of cardiac muscle. The data are consistent with a major role for Ca2(+)-induced Ca2+ release in cardiac activation, whereas the role for Ins(1,4,5)P3 may be to modulate, rather than directly stimulate, SR Ca2+ release. PMID- 2309922 TI - Body size, medullary thickness, and urine concentrating ability in mammals. AB - B. H. Blake (Comp. Biochem. Physiol. A Comp. Physiol. 58: 413-419, 1977.) and W. A. Calder and E. J. Braun (Am. J. Physiol. 244 (Regulatory Integrative Comp. Physiol. 13): R601-R606, 1983.) have predicted that urine concentrating ability of mammals should decline with increasing body mass (M, in kg) as M-0.08. Edwards (29), on the other hand, speculated that concentrating ability should be independent of body mass. Using information compiled from the literature for 245 species of mammals, I examined the scaling of urine concentrating ability with body mass. Maximum urine concentration (Uosm, in mosmol/kgH2O) declined exponentially with body mass as Uosm = 2,564 M-0.097, and generally only the smallest species (less than 400 g) could produce urine with an osmolality greater than 4,000 mosmol/kgH2O. Medullary thickness (MT, in mm) and, therefore, the length of the loop of Henle, increased with body mass as MT = 8.147 M0.129. The thickness of the medulla relative to the size of the kidney (RMT), however, declined with body size (RMT = 5.408 M-0.108). The relative thickness of the medulla accounted for only 59% of the variability among species in concentrating ability, indicating that there are other morphological or physiological factors that significantly influence urine concentrating ability. PMID- 2309923 TI - Effects of hyperosmolality and diuretics on heat-induced limb vasodilation in baboons. AB - Dehydration attenuates the increase in limb skin blood flow elicited by environmental heating (EH). This study sought to determine which of the two primary effects of dehydration, increased body fluid osmolality or decreased body fluid volume, was primarily responsible for this cutaneous vasoconstrictor bias in baboons. Unanesthetized chronically instrumented baboons were exposed to EH while in euhydrated state, after 65-69 h of water deprivation (dehydration), after infusion of a small volume of hypertonic (20%) saline to raise plasma osmolality and sodium concentration to dehydration levels, and after injections of the diuretic furosemide over a 64-h period to produce an isosmotic fall in extracellular fluid volume. EH consisted of an acute elevation of ambient temperature to 39.5-42.0 degrees C until internal temperature reached 39.5-39.8 degrees C. The normal increases in external iliac artery blood flow and iliac vascular conductance during EH were unchanged by hyperosmolality but were attenuated by 39 and 31%, respectively, after furosemide treatment and by 42 and 46%, respectively, during dehydration. Thus the fall in extracellular fluid volume is the component of dehydration that attenuates the increase in hindlimb blood flow during EH in the same way as dehydration itself. PMID- 2309924 TI - Effect of water or saline intake on heat-induced limb vasodilation in dehydrated baboons. AB - Dehydration markedly attenuates the increase in hindlimb blood flow elicited by environmental heating (EH) in baboons. This study sought to determine the importance of gradually produced increases in body fluid osmolality and decreases in body fluid volume in producing this attenuation. The hindlimb blood flow increases during EH of seven unanesthetized chronically instrumented baboons were examined during euhydration, dehydration (64-68 h of water deprivation), and after ad libitum oral rehydration with either water or a hyperosmotic saline solution. EH consisted of acute exposure to ambient temperatures of 38-42 degrees C until internal temperature reached 39.5 degrees C. Dehydration depressed the maximal external iliac artery blood flow (MIBF) and iliac vascular conductance (IVC) attained during EH in the euhydrated state by 37 and 43%, respectively. Rehydration with either water or saline solution, however, restored maximal MIBF and IVC to euhydrated levels. Because plasma osmolality remained at dehydrated levels after rehydration with saline, hyperosmolality does not produce the dehydration-induced attenuation in hindlimb blood flow. PMID- 2309925 TI - Antiserum against tumor necrosis factor enhances lipopolysaccharide fever in rats. AB - The role of tumor necrosis factor (TNF, cachectin), a putative endogenous pyrogen, was investigated by comparing fever and plasma TNF levels after the intraperitoneal and intramuscular injection of 10 micrograms/kg lipopolysaccharide (LPS) into male Sprague-Dawley rats and by neutralization of endogenous TNF using TNF antiserum. An intraperitoneal injection of LPS caused a biphasic fever that lasted approximately 6.5 h. TNF levels in these rats peaked at 657 +/- 222 U/ml at 1 h then declined to virtually undetectable levels by the fourth hour. The intramuscularly injected animals showed a lower monophasic fever and low sustained TNF levels (40 +/- 10 U/ml at 1 h, 18 +/- 11 U/ml at 4 h). In a second study, an antiserum that had been shown to neutralize rat TNF was injected intraperitoneally 2 h before the intramuscular injection of 10 micrograms/kg LPS. Control rats were injected with normal rabbit serum before LPS. During the second hour after the injection of LPS, the animals that received the antiserum developed fevers that tended to be lower than those seen in the rats that were injected with control serum (0.33 +/- 0.06 vs. 0.58 +/- 0.1), although this difference was not significant. However, during the third through eighth hours after LPS, the antiserum-injected rats had mean body temperatures that were significantly higher than those of the control rats (1.62 +/- 0.11 vs. 1.07 +/- 0.09; P = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309926 TI - Thyroxine transport from blood to brain via transthyretin synthesis in choroid plexus. AB - The transport of thyroxine from the bloodstream to the brain and the synthesis and secretion of transthyretin (formerly called prealbumin) were studied in rats and in sheep choroid plexus perfused in vitro. Rat choroid plexus contained 4.4 micrograms and rat liver 0.39 micrograms transthyretin mRNA per gram wet tissue. The specific radioactivity of transthyretin isolated from cerebrospinal fluid of rats 60 min after intravenous injection of [14C]leucine was greater than 50 times that of transthyretin from serum. After adding [14C]leucine to the perfusion medium of an in vitro perfused sheep choroid plexus, highly radioactive transthyretin was isolated from freshly secreted cerebrospinal fluid collected from the exposed choroid plexus surface. Secretion of newly synthesized transthyretin into the perfusion medium could not be demonstrated. After intravenous injection of [125I]-thyroxine into rats, a maximum in the curve of radioactivity in tissue plotted against time after injection was observed first for choroid plexus, thereafter for cerebrospinal fluid, and still later for cortex and striatum. Based on the obtained data, a hypothesis is derived for the mechanism of the transport of thyroid hormones from the bloodstream to the brain involving transthyretin synthesized in choroid plexus and secreted into the cerebrospinal fluid. PMID- 2309927 TI - Apparent influence of metabolism on cardiac isomyosin profile of food-restricted rats. AB - In addition to thyroid hormone, carbohydrate oxidation appears to influence the relative distribution of rodent cardiac isomyosin (V1, V2, V3), especially in diabetic, thyroid-deficient, and food-restricted animals. To determine whether metabolic variations within the myocardium itself contribute to cardiac isomyosin distribution, food-restricted rats (predominantly V3) were treated with oxfenicine, a cardiospecific inhibitor of fatty acid metabolism. Animals received a mixed diet (50% carbohydrates) ad libitum (FE-M) or in restricted quantities (45% of FE-M; FR-M). Additional food-restricted animals received oxfenicine (75 mg/kg, twice daily) and either a mixed diet (FR-M-OXF) or a high-carbohydrate diet (75% carbohydrates, FR-HC-OXF). After 3 wk, hemodynamic and metabolic measurements were taken, serum 3,5,3'-triiodothyronine (T3) levels were measured, and cardiac citrate synthase (CS) activity and isomyosin distribution (percent V1, V2, V3) was determined. Relative to the FE-M group, thyroid status (CS, T3) was reduced only in the FR-M-OXF and the FR-HC-OXF groups (P less than 0.05). Oxfenicine treatment of food-restricted animals partially preserved the isomyosin profile of the FE-M group (P less than 0.05), suggesting that, within the context of food restriction, cardiac metabolism can influence cardiac isomyosin distribution independently of thyroid status. PMID- 2309928 TI - Evidence of a slow-to-fast fiber type transition in skeletal muscle from spontaneously hypertensive rats. AB - The histochemical, biochemical, and electrophysiological properties of selected muscles were evaluated in spontaneously hypertensive rats (SHR) and compared with their normotensive Wistar-Kyoto (WKY) counterparts. As early as 4 wk of age, slow muscles (soleus) of SHR displayed a significant alteration in fiber type distribution with a decrease of slow-twitch fibers (from 64 to 53%) and a simultaneous increase of type IIA-fibers (from 19 to 39%). In addition, soleus from young SHR had a significant enhancement of both oxidative (citrate synthase, 3-hydroxyacyl-CoA dehydrogenase) and glycolytic [lactate dehydrogenase (LDH)] capacities, which could be partly related to a capillary rarefaction. During development (from the 4th to the 12-14th wk), in the soleus muscle the histochemical differences between SHR and WKY were amplified, whereas most of the enzymatic differences between strains were abolished, except for a significantly higher LDH activity. These histochemical changes had only marginal repercussions on soleus electrophysiological properties. SHR animals had a significantly higher basal metabolic rate, which could not be accounted for by elevation of thyroid hormones. The origin of the slow-to-fast fiber type transition in slow muscle remains unclear but could be related to the increased level of plasma catecholamines in SHR. Indeed, chronic treatment of rats with a beta 2-receptor agonist has been reported to cause slow-to-fast muscle fiber transition [R. J. Zeman, R. Ludemann, T. G. Easton, and J. D. Etlinger. Am. J. Physiol. 254 (Endocrinol. Metab. 17): E726-E732, 1988]. PMID- 2309929 TI - Parabrachial nucleus modulation of vasopressin release. AB - The present studies examine the contribution of the ventrolateral lateral parabrachial nucleus (VLLPBN) to the regulation of plasma arginine vasopressin (PAVP) release in response to either a baroreceptor or osmotic stimulus. These studies were carried out in rats with bilateral electrolytic lesions of the VLLPBN. Baroreceptor-induced stimulation of PAVP was achieved by decreasing blood pressure with combined blockade of the renin-angiotensin system with captopril (3 mg/kg iv) and the sympathetic nervous system with chlorisondamine, (11 mg/kg sc). Osmotic release of vasopressin was elicited by a 2-h intravenous infusion of hypertonic saline, (3.0 meq/ml, 0.01 ml/min). Blood pressure and heart rate were monitored throughout the experiments. Blood samples for determination of PAVP, plasma osmolality (posm), plasma sodium (PNa), and plasma potassium (PK) were taken before (base line) and after treatment in each study. The VLLPBN-lesioned rats secreted significantly more vasopressin in response to hypotension produced by combined renin-angiotensin and sympathetic nervous system blockade than did control rats. There was no significant difference between groups in Posm, PNa, or PK, or cardiovascular changes. In contrast, hypertonic saline infusion did not produce any differential changes between groups. PMID- 2309930 TI - Brain glucoprivation and ketoprivation do not promote ingestion in the suckling rat pup. AB - We examined the possibility that brain glucose or ketone availability may control suckling or precocious feeding in the preweanling rat. Brain glucoprivation induced by 5-thio-D-glucose injection into the 4th ventricle did not increase feeding on orally infused milk until 30 days of age, although hyperglycemia was evoked as early as 9 days by the same treatment. Plasma ketone levels varied with suckling status, but pharmacological blockade of hepatic free fatty acid oxidation, which restricts ketone availability (ketoprivation), failed to increase suckling. Because the suckling rat can switch energy substrates under nutritional duress, we combined glucoprivation and ketoprivation. Feeding was suppressed, and suckling was not affected. Finally, we injected ketones into the 3rd brain ventricle and found that they increased feeding. Thus, in contrast to the adult rat, reduced glucose or ketone utilization by the brain does not increase food intake in the preweanling, but increased circulating and brain ketone concentrations may arouse feeding. PMID- 2309931 TI - Neuropeptide Y in the hypothalamus: effect on corticosterone and single-unit activity. AB - The purpose of the present study was to determine whether neuropeptide Y (NPY) acts within the hypothalamic paraventricular nucleus (PVN) or the suprachiasmatic nucleus (SCN) to alter circulating levels of corticosterone and to evaluate the effects of NPY on the single-unit response of PVN and SCN neurons using the hypothalamic slice preparation. Blood levels of corticosterone were determined in groups of rats that received microinjections of NPY or saline (Sal) into the PVN or SCN. NPY injected into the PVN 4 h after light onset resulted in corticosterone levels of 13.15 +/- 2.18 (SE) micrograms/dl within 1 h, which were significantly higher than the corticosterone levels of 4.08 +/- 1.78 micrograms/dl seen in rats receiving Sal injections. In contrast, no significant differences were observed in circulating levels of corticosterone between groups of rats 1 or 4 h after NPY or Sal microinjection into the SCN. In the hypothalamic slice, NPY was found to produce primarily inhibitory responses in both SCN and PVN neurons. Forty-nine percent of the SCN units examined were inhibited. In addition, another 20% of the neurons tested in the SCN displayed excitation followed by more sustained inhibition. In the PVN, 45% of the units examined were inhibited by NPY, however, nearly 30% of the remaining neurons were significantly excited by NPY. In summary, NPY alters the electrical activity of both SCN and PVN neurons but appears to act only within the PVN to influence circulating levels of corticosterone. These and other data indicate that NPY acts as an important neurochemical messenger within several hypothalamic sites. PMID- 2309932 TI - Inhibitory effect of renal nerve activity during canine anaphylactic hypotension. AB - We have examined baroreceptor regulation of renal nerve activity (RNA) during anaphylactic hypotension that affects renal nerve activity. In anesthetized dogs, mean blood pressure (MBP), heart rate (HR), and RNA were simultaneously measured. To test for a normally functioning baroreceptor reflex in each animal, a transient hypotension was induced by an intravenous injection of sodium nitroprusside (4 micrograms/kg). Nitroprusside produced a reflex increase in RNA (+63 +/- 12% at -20 mmHg and +139 +/- 8% at -40 mmHg) and HR (+13 +/- 1 beats/min at -20 mmHg and +21 +/- 2 beats/min at -40 mmHg). However, intravenous administration of Ascaris suum antigen in animals with an intact neuraxis caused a decrease in RNA (-15 +/- 14% at -20 mmHg and -42 +/- 11% at -40 mmHg blood pressure during the antigen-induced hypotension) in parallel with a fall in systemic blood pressure. HR responses were -5 +/- 2 beats/min at -20 mmHg and -10 +/- 1 beats/min at -40 mmHg during the hypotension induced by the antigen. In animals with combined denervation of the carotid sinus and vagal nerves, HR did not change significantly during anaphylactic hypotension. However, a decrease in RNA remained (-60 +/- 4% at -20 mmHg and -72 +/- 4% at -40 mmHg of hypotension). The decrease in RNA after antigen administration was significantly greater after denervation than in animals with an intact neuraxis. These results indicate that systemic baroreceptor reflex control of RNA is reduced during anaphylactic hypotension. Impaired reflex control of sympathetic nerve activity may result from an impairment of sympathetic outflow through the central nervous system. PMID- 2309933 TI - Diazepam inhibits stimulating effect of cooling preoptic area on antibody production. AB - To clarify the mechanism of the stimulating effect of fever on the primary antibody response, rats were immunized with sheep erythrocytes, and a fever-like response was induced by cooling the preoptic area for five days. Diazepam, 0.5 mg/kg, given daily during the cooling time, did not affect the normal antibody response of the control animals nor did it prevent the rise in body temperature elicited by cooling the preoptic area but it did, nevertheless, strongly reduce the stimulating effect of this procedure on antibody production. A smaller reduction of this effect was also seen in adrenalectomized rats in which a physiological and stable plasma level of corticosterone was maintained. Because diazepam suppresses some sympathetic and endocrine responses to stress, these data suggest that the effect of cooling the preoptic area on the primary antibody response, and, by inference, that of fever, is to a large extent mediated by the adrenal and other stress response or responses to the cold stimulus. The results do not, however, exclude the possibility of an additional, direct effect of the elevated body temperature on immunocompetent cells. PMID- 2309934 TI - Diluting segment in kidney of dogfish shark. II. Electrophysiology of apical membranes and cellular resistances. AB - Diluting segments from the bundle zone of the dogfish shark kidney were perfused in vitro and the electrophysiological characteristics of this segment investigated using conventional microelectrodes and cable analysis. In 21 tubules perfused with symmetrical Ringer solutions the average transepithelial voltage (Vte), transepithelial conductance (Gte), and equivalent short circuit current (Isc) were 8.7 +/- 0.6 mV, 91.3 +/- 10.2 mS/cm2, and 641 +/- 48 microA/cm2, respectively. Microelectrode impalements in 52 cells yielded values for the basolateral membrane voltage (Vb) and an estimated apical membrane fractional resistance (fRa) of -57.5 +/- 1.3 mV and 0.896 +/- 0.008, respectively. All of these parameters were distributed in a Gaussian manner. Liminal furosemide (10( 4) M) abolished Isc, hyperpolarized apical membrane voltage (Va) and Vb, increased Gte, and reduced fRa. The apical membrane was predominantly conductive to K+: increasing luminal K+ from 5 to 49.7 mM resulted in an apical depolarization of 41.2 mV and a fall in fRa and luminal Ba2+ (1 mM) depolarized Va by 14.3 mV and increased fRa. The apical transference number for K+ was 0.74 +/- 0.07. The cellular and paracellular resistances were estimated from the effects of luminal Ba2+ on fRa and Gte. The cell conductance represented approximately 45% of Gte, with the primary resistance barrier located at the apical membrane: apical membrane resistance was 59.7 +/- 16.0 and basolateral membrane resistance was 5.9 +/- 2.3 omega.cm2. From these resistance values together with the passive permeability (PNa/PCl) of 2.5 determined previously, the ratio of net Cl- absorption to net transcellular Na+ absorption was determined to be 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309935 TI - Hemodynamic effects of calcitonin gene-related peptide in spontaneously hypertensive rats. AB - Systemic and regional hemodynamic effects of intravenously injected calcitonin gene-related peptide (CGRP), 220 and 650 pmol, were compared in nine Wistar-Kyoto (WKY) and nine spontaneously hypertensive rats (SHR). CGRP (higher dose) reduced mean arterial pressure (from 135 +/- 2 to 83 +/- 2 and from 179 +/- 4 to 116 +/- 3 mmHg; P less than 0.01, each, in WKY and SHR, respectively) through a fall (-38 +/- 4 and -40 +/- 3%; P less than 0.01) in total peripheral resistance associated with an unchanged cardiac output and an increased heart rate. The decreases in arterial pressure and total peripheral resistance were not different between these two strains. Of particular significance were the highly selective reductions in organ vascular resistances, being greatest in the cutaneous (-78 +/ 3 and -67 +/- 4%) and gastric (-80 +/- 3 and -84 +/- 2%) circulations in WKY and SHR, respectively (P less than 0.01). Reduction in coronary, cerebral, and hepatic vascular resistances, although significant (P less than 0.05, at least), were only moderately reduced compared with the two former circulations. These effects were similar in WKY and SHR and demonstrate that CGRP is a highly selective and potent natural vasodilating peptide that has the most striking effects in skin and stomach, suggesting possible modulator functions in regulating certain regional hemodynamics. PMID- 2309936 TI - Adrenergic effects on thyroxine 5'-deiodinase in brown adipose tissue of lean and ob/ob mice. AB - Genetically obese, ob/ob, mice have an impaired capacity to increase the level of thyroxine 5'-deiodinase (T5'D) in their brown adipose tissue (BAT) when they are exposed to cold. Yet they are able to secrete norepinephrine (NE) from the nerves of their BAT in response to cold and are apparently refractory to this action of NE. The principal objective was to find out whether injected NE could increase T5'D in BAT of the ob/ob mouse. A secondary objective was to elucidate the nature of the adrenergic receptor(s) involved in this response in lean and ob/ob mice. Injection of NE increased T5'D in BAT of lean mice within 3 h. It also increased T5'D in BAT of ob/ob mice but to a lesser extent. Basal T5'D activity in BAT of ob/ob mice was greater than that seen in BAT of lean mice because of the greater size of the tissue. Neither isopropylnorepinephrine nor phenylephrine alone could increase T5'D activity, but a combination increased it almost as well as did NE, although to a lesser extent in ob/ob mice than in lean mice. Both a beta adrenergic antagonist (propranolol) and an alpha 1-adrenergic antagonist (prazosin) could inhibit the effect of NE. The acute effect of NE on metabolic rate of intact mice also involves an action of both beta- and alpha 1-adrenergic receptors. The beta-adrenergic component appears to be defective in the ob/ob mouse. PMID- 2309937 TI - Ventromedial hypothalamic lesions abolish compensatory reduction in energy expenditure to weight loss. AB - Weight loss through caloric restriction produces compensatory reductions in the whole body energy expenditure of normal rats. The present experiment determined whether rats who had become obese after ventromedial hypothalamic (VMH) lesions displayed this metabolic defense of body weight. Obese VMH-lesioned and normal weight control female rats were assigned to one of three weight maintenance conditions (100, 90, and 80% of previously maintained body weight). Postabsorptive oxygen consumption was then measured by open-circuit respirometery while, simultaneously, behavioral activity was measured by stabilimeter. A marked decline in resting energy expenditure and behavioral activity, seen in control rats after weight loss, was absent in VMH-lesioned rats. These results suggest that VMH lesions impair the ability to adjust energy expenditure in response to alterations in nutritional status, a response that normally serves to stabilize body weight at a regulated level. PMID- 2309938 TI - Osmotic regulation of vasopressin and oxytocin release is rate sensitive in hypothalamoneurohypophysial explants. AB - Explants of the hypothalamoneurohypophysial system (HNS) from rats were maintained in perifusion culture and exposed to 15-18 mosmol/kgH2O changes in the osmolality of the culture medium achieved by increasing or decreasing the NaCl concentration. The rate of change in osmolality was either 0.14 +/- 0.01 mosmol/min (2%/h), 0.27 +/- 0.02 mosmol/min (5%/h), or 1.7 +/- 0.2 mosmol/min (30%/h). Vasopressin (VP) and oxytocin (OT) release into the culture medium was determined. Increased VP release was detected after all three rates of increase, but the peak response occurred sooner and in response to a smaller increment in osmolality during the 5% rate of increase compared with the 2% rate of increase. Peak VP release occurred during the first 10 min of the 30% pulse and was significantly greater than the response to the 2 and 5% rates (P less than 0.05). The increase in VP release was sustained throughout the 3 h of hypertonicity during the 2% pulse, but not during the 5 and 30% osmotic pulses. A significant decrease in VP release was observed on returning the osmolality to basal at both the 2 and 5% rate, but this inhibition was followed by a rebound in VP release that started during the decrease in osmolality and significantly exceeded basal VP release. A significant inhibition of VP release also was observed when explants were exposed to hypotonic pulses at the 2 and 5% rate. At both rates, the inhibition of VP release corresponded to a 5- to 7-mosmol/kgH2O decrease in osmolality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309939 TI - Generation of vasoactive substances in trout and rat plasma by trypsin and kallikrein. AB - In the preceding study we demonstrated kallikrein-like enzymatic activity in trout tissues and showed that kallikrein incubated with trout plasma (T60K) produces a vasopressor substance(s). The present study further examines the effects of T60K in fish and mammals in vitro and in vivo. T60K produced a dose dependent pressor response in both trout and rats, whereas kallikrein-activated rat plasma (R60K) was pressor in trout and depressor in rats. Captopril did not affect the response of rats to T60K or R60K. Phenoxybenzamine attenuated the T60K response in trout but not in rats, thus T60K effects in trout are partially mediated through catecholamines. Blockade of angiotensin II (ANG II) receptors in rats with [Sar1,Ala8]-ANG II abolished the pressor effects of T60K. T60K produced dose-dependent contractions in isolated trout and rabbit arteries; ANG II was ineffective in trout arteries. T60K-contracted trout arteries were relaxed by atrial natriuretic peptide and forskolin, whereas diltiazem and sodium nitroprusside were without effect. [Sar1,Ala8]ANG II inhibited T60K-induced contractions of rabbit arteries and relaxed rings previously contracted with T60K. The active component of T60K has a molecular weight less than 10,000, is heat stable, and is inactivated by peptidases. It is immunologically different than mammalian angiotensins but binds to and displaces radiolabeled ANG II from ANG II receptors. These results suggest that kallikrein forms a vasoactive substance(s) in trout plasma that is neither bradykinin nor ANG II but is similar to the latter in its pharmacological effects. PMID- 2309940 TI - Somnogenic, pyrogenic, and hematologic effects of experimental pasteurellosis in rabbits. AB - Previous work has demonstrated that intravenous inoculation of rabbits with various microorganisms induces complex time-dependent alterations in sleep as well as other pathophysiological effects typically associated with infectious disease. To evaluate the effects of bacterial challenge that more closely resembles naturally developing disease, we inoculated rabbits with Pasteurella multocida, a common pathogen of this species, using routes of administration that mimic normal routes of exposure. Biphasic sleep alterations characterized initially by enhanced slow-wave sleep and later by decreased slow-wave sleep occurred after intravenous, intramuscular, subcutaneous, or intranasal inoculation. Rapid-eye-movement sleep was inhibited for most of the 48-h period after inoculation. Inoculation by all four routes also induced fever and qualitatively similar hematologic changes. However, the magnitude and specific temporal patterns of both somnogenic changes and other pathophysiological effects varied with the route of inoculation. PMID- 2309941 TI - Effect of gastrointestinal flora on body temperature of rats and mice. AB - The purpose of these experiments was to test the hypothesis that gut flora influences the body temperature of rodents. Rats and mice were implanted with biotelemetry transmitters that enabled us to record both abdominal temperature and activity for long periods of time. Rats given nonabsorbable antibiotics in their drinking water, which reduced their gut flora, had a marked decrease in both their daytime and nighttime temperatures. Similar results were found with germfree mice. The circadian rhythms in body temperature of germfree and conventionalized mice were not different. However, the body temperatures of the germfree mice were lower than those of the conventionalized mice during both the daytime and nighttime. The decrease in body temperature in the germfree mice was not related to changes in activity. These results support the hypothesis that gut flora has a tonic stimulatory effect on both the daytime and nighttime body temperature of rodents. PMID- 2309942 TI - Toward a clinical model of psychotherapy for depression, II: An integrative and selective treatment approach. AB - This is the second in a two-part series on psychotherapy for depression. Considering depression as a spectrum phenomenon, the author goes beyond manual based diagnosis to suggest criteria for the use of psychodynamic, cognitive, or interpersonal psychotherapy, with or without pharmacotherapy. He proposes a clinical model that is both integrative and selective and recommends shifting and sharing different therapeutic perspectives in tailoring treatment to the depressed individual. PMID- 2309943 TI - Clinical correlates of the deficit syndrome of schizophrenia. AB - The authors propose using primary and enduring negative or deficit symptoms for dichotomizing schizophrenic patients into two groups, deficit and nondeficit. The validity of this approach was examined by comparing 17 deficit and 17 nondeficit patients for differences in premorbid adjustment and degree of neurological impairment. Deficit patients were characterized by poorer premorbid adjustment and greater neurological impairment. Neurological impairment was not related to premorbid adjustment in either group or in the total patient population. These findings support the utility of deficit symptoms for defining a more homogeneous subgroup of schizophrenia. PMID- 2309944 TI - Subjective awareness of abnormal involuntary movements in chronic schizophrenic patients. AB - The authors examined the effects of verbal and visual feedback on subjective awareness of involuntary movements in 20 chronic schizophrenic patients. At initial evaluation only 25% of the patients were fully aware of their movement disorder. Both verbal and visual feedback resulted in significant immediate enhancement of awareness. However, assessment of awareness 2 weeks later showed a return to prefeedback baseline levels. Lack of awareness of involuntary movements was associated with a lack of awareness of psychiatric disorder, and both were associated with a longer duration of illness. PMID- 2309945 TI - Delusions in newly admitted residents of nursing homes. AB - Two psychiatrists, using standardized clinical examinations, found that 21% of 125 patients newly admitted to nursing homes had delusions. The psychiatric disorders associated with these delusions are described. Delusional patients were more behaviorally disturbed before admission than nondelusional patients. These behavior problems were often the reason for admission, and they persisted after admission. Nursing home staff members infrequently identified and often inappropriately treated delusional patients. Since delusions are an important potentially treatable cause of behavior problems in nursing home residents, the authors suggest ways to improve the recognition and management of delusions. PMID- 2309946 TI - Personality and emotional disorder in a community sample of migraine headache sufferers. AB - To investigate whether individuals who suffer from chronic, severe headaches have more personality abnormalities or emotional disorders than their healthy counterparts, 162 young adults with classical migraine, ascertained by community survey, were compared to matched control subjects without migraine. On the General Health Questionnaire, the prevalence of psychological symptoms among the migraine subjects was 2.5 times the prevalence among the control subjects. The migraine sufferers also had significantly higher scores on the psychoticism (women only), neuroticism, and lie scales of the Eysenck Personality Questionnaire. Frequency of migraine attacks was not related to scores on any of the scales. These results suggest that classical migraine is associated with psychological abnormalities. PMID- 2309947 TI - Greater left cerebral hemispheric metabolism in bulimia assessed by positron emission tomography. AB - Eight women with bulimia and eight age- and sex-matched normal control subjects were studied with positron emission tomography using [18F]-fluorodeoxyglucose (FDG) as a tracer of brain metabolic rate. Subjects performed a visual vigilance task during FDG uptake. In control subjects, the metabolic rate was higher in the right hemisphere than in the left, but patients with bulimia did not have this normal asymmetry. Lower metabolic rates in the basal ganglia, found in studies of depressed subjects, and higher rates in the basal ganglia, reported in a study of anorexia nervosa, were not found. This is consistent with the suggestion that bulimia is a diagnostic grouping distinct from these disorders. PMID- 2309948 TI - A community study of anxiety in children and adolescents. AB - The authors used an epidemiologic approach to investigate rates, symptoms, and behavioral concomitants of anxiety across the child and adolescent age span. They drew 210 children aged 8, 12, and 17 in equal numbers from a community sample and evaluated them with structured diagnostic assessments. They found anxiety to be the most frequently reported type of psychopathology across all three age groups. Although the prevalence of any anxiety symptom remained constant, specific types of anxiety varied with age. Age differences in nonanxiety behavior were found between subjects with and without anxiety, particularly with regard to interpersonal dysfunction. PMID- 2309949 TI - Correlates of anxiety in psychiatrically hospitalized children and their parents. AB - The authors separated 100 children hospitalized in a child psychiatry service into three groups according to their level of anxiety on the basis of the responses of the children and their parents to diagnostic interviews. Differentiation of the groups of children was validated by independent test instruments. Results of tests administered to the children and their parents revealed significant relationships between anxiety in the adults and in the children. In addition, parents of anxious children reported more SCL-90-R symptoms as well as more negative family relations than parents of nonanxious children and the more severely anxious children had higher rates of dysthymia and negative life events. PMID- 2309950 TI - Evaluation of a Mental Illness Awareness Week program in public schools. AB - The authors evaluated the impact of a Mental Illness Awareness Week program on the attitudes of adolescents attending public school toward seeking help for mental health problems and toward psychiatrists. Most students involved in the program liked it and indicated that they were interested in learning more about mental health topics. Students in the program showed more favorable attitudes toward seeking help and toward psychiatrists than a comparison group of students who did not participate in the program. The authors discuss the evidence for enduring effects of the program. The results support continued development of Mental Illness Awareness Week programs for adolescents in the public schools. PMID- 2309951 TI - Transethnic adoption and personality traits: a lesson from Japanese orphans returned from China to Japan. AB - The authors interviewed 25 Japanese who had been left as orphans in China at the end of World War II and who had recently returned to Japan with their Chinese spouses after almost four decades. It was found that even though they had been raised as Chinese culturally for almost their entire lives, most of these subjects had retained certain Japanese personality traits and social behavior from early childhood, and these characteristics distinguished them from their Chinese counterparts. PMID- 2309952 TI - Sexual assault and psychiatric disorders among a community sample of women. AB - The authors examined the relationships between sexual assault and psychiatric disorders in a sample of 1,157 women 18-64 years old in the North Carolina site of the NIMH Epidemiologic Catchment Area Program. The results suggest that sexual assault is a risk factor for a number of psychiatric disorders. In addition, several characteristics of the assault among sexual assault victims were significantly related to one or more psychiatric disorders. However, there was no clear pattern relating characteristics of the assault to the risk of specific psychiatric disorders. PMID- 2309953 TI - Guns and suicide: possible effects of some specific legislation. AB - The authors describe suicide rates in Toronto and Ontario and methods used for suicide in Toronto for 5 years before and after enactment of Canadian gun control legislation in 1978. They also present data from San Diego, Calif., where state laws attempt to limit access to guns by certain psychiatric patients. Both sets of data indicate that gun control legislation may have led to decreased use of guns by suicidal men, but the difference was apparently offset by an increase in suicide by leaping. In the case of men using guns for suicide, these data support a hypothesis of substitution of suicide method. PMID- 2309954 TI - Patterns of sex differences in negative symptoms and social functioning consistent with separate dimensions of schizophrenic psychopathology. AB - In 220 schizophrenic twins, men had greater asociality-withdrawal and poorer premorbid social competence than women but there were no sex differences in symptoms, suggesting that negative symptoms and social functioning reflect different processes in the development and manifestation of schizophrenia and that they should be examined separately. PMID- 2309955 TI - Relationship of cognitive factors to CSF corticotropin-releasing hormone in depression. AB - The authors investigated the relationship between items on the Beck Depression Inventory and CSF levels of corticotropin-releasing hormone (CRH) in 17 depressed patients. Linear regression analysis showed that self-accusation, expectation of punishment, and crying accounted for 82% of CRH variance. PMID- 2309956 TI - Is the carbamazepine-phenelzine combination safe? PMID- 2309957 TI - Affective disorder following use of phenylpropanolamine. PMID- 2309958 TI - Change in response to pemoline at puberty. PMID- 2309959 TI - An atypical responder to clozapine. PMID- 2309960 TI - An unusual case of Capgras' syndrome. PMID- 2309961 TI - Fluoxetine for the treatment of compulsive facial picking. PMID- 2309962 TI - Fluoxetine for adolescents with obsessive-compulsive disorder. PMID- 2309963 TI - Antidepressants and mania. PMID- 2309964 TI - Bulimia associated with sexual trauma. PMID- 2309965 TI - ECT as prophylactic treatment for bipolar disorder. PMID- 2309966 TI - Sleep disturbance in posttraumatic stress disorder. PMID- 2309967 TI - Differential diagnosis of schizophrenia and multiple personality disorder. PMID- 2309968 TI - Oxazepam and carbamazepine for alcohol withdrawal. PMID- 2309969 TI - Childhood panic disorder with agoraphobia. PMID- 2309970 TI - Children with panic disorder. PMID- 2309971 TI - Biases in family assessments of depression in patients with Alzheimer's disease. PMID- 2309972 TI - Late luteal phase dysphoric disorder and DSM-III-R. PMID- 2309973 TI - Duty to protect and gun control. PMID- 2309974 TI - An occupational hazard of psychiatrists. PMID- 2309975 TI - Buildup of proactive inhibition as a function of temporal spacing and adult age. AB - Glenberg's theory of temporal distinctiveness (Glenberg, 1987; Glenberg & Swanson, 1986) was used to examine whether the buildup of proactive inhibition (PI) may be interpreted as an overloading of temporal retrieval cues. The Brown Peterson task was selected on the basis of the assumption that successful performance on such a task requires the use of a recency rule where the subject must use temporal cues to retrieve the contents of the most recent study list. Two variables were manipulated that were presumed to affect the utilization of temporal cues: length of intertrial interval (ITI) (0 or 90 s) and adult age (young or elderly). Glenberg's theory suggests that temporal spacing improves memory by enhancing the distinctiveness of temporal retrieval cues. Thus, it was predicted that PI buildup should be less in the 90-s condition than in the 0-s condition. Assuming that older adults are more sensitive to the overloading of temporal cues, it was anticipated that older adults would experience a greater buildup of PI than younger adults at the 0-s condition. Results showed that although PI buildup varied with length of ITI, it did not vary with adult age. Analysis of delayed measures of recall, recognition, and temporal memory suggested that a retrieval interpretation based on Glenberg's theory is insufficient as an explanation of the current results; encoding difficulties also appear to contribute to the buildup of PI. PMID- 2309976 TI - Gestalts are more closely associated with performance on a discrimination task than are component stimuli. AB - Distance, similarity, and other components of the physical stimulus but also gestalts are associated with the ability to discriminate between two objects. The present research bears on this confound. Identical lines were added to the opening and closing bracket of a pair of brackets to form two identical rectangles. A stimulus consisted of either one or two of these brackets, lines, or rectangles. Subjects indicated as quickly as possible whether one or two objects occurred. The discriminations between two near brackets and two near lines were more difficult than the discrimination between two near rectangles. A large distance between two objects improved the bracket and line discriminations more than the rectangle discrimination. Single brackets and lines did not result in poorer performance than did single rectangles. These results disconfirm the distance, similarity (including relational similarity), good continuation, location of geometric centers, size, closedness, symmetry, spatial frequency, redundancy, and number of lines component stimulus predictions at least twice. Both the two near brackets and the two near lines produce single gestalts, whereas each remaining 2-object stimulus results in two gestalts. Therefore, gestalts predicted performance better than did component stimuli. Another result was that the 2-object responses were faster than the 1-object responses for far objects. PMID- 2309977 TI - Need to educate cancer survivors. PMID- 2309978 TI - Heterogeneity of acute "undifferentiated" leukemia of childhood: ultrastructural, immunophenotypic, and karyotypic analyses. AB - The present study was undertaken in an attempt to reclassify the 19 cases of childhood acute undifferentiated leukemia (AUL) diagnosed at our institution during the past 12 years. Based on ultrastructural and immunophenotypic data, seven of the cases were reclassified as lymphoid, nine as myeloid, and three remain unclassifiable. Clinical features, clonal karyotypes, and responses to treatment were also examined. Abnormal clonal karyotypes were found in 16 of 17 cases, including eight cases with translocations, three with monosomy 7 or 7q, and one with numerous complex structural rearrangements. Fourteen patients had greater than 10% French-American-British L2 blasts in bone marrow. Although nine of 15 patients who initially received induction therapy for acute lymphoblastic leukemia (ALL) achieved remission, only one patient is a long-term survivor. Only one of 10 patients who received therapy for acute nonlymphoblastic leukemia during the course of their disease remains a long-term survivor. These data suggest that the majority of cases of AUL can be reclassified as either myeloid or lymphoid leukemias, that AUL is associated with a high frequency of chromosomal abnormalities, and that AUL carries a very poor prognosis. PMID- 2309979 TI - Treatment of meningeal relapse in childhood acute lymphoblastic leukemia: II. A prospective study of intellectual loss specific to CNS relapse and therapy. AB - Changes in intellectual function during the course of treatment for acute lymphocytic leukemia were studied. Twenty-four children had baseline psychological evaluations and annual reevaluations for 3-6 years postdiagnosis. Treatment in all patients included combination chemotherapy, 2,400 cGy prophylactic cranial irradiation, and intrathecal methotrexate. Central Nervous System (CNS) relapse occurred in eight of these children. It was then treated with 3,000 cGy cranial plus 1,800 cGy spinal irradiation. Patients who remained in continuous complete remission showed no decline in global intelligence quotient (IQ). Patients who experienced CNS relapse had a mean decline of 16 IQ points by 3 years postdiagnosis and the long-term survivors displayed a mean loss of 25 IQ points 5-6 years postdiagnosis. Three of the five long-term survivors of CNS relapse function within the retarded range of mental ability and require special education. The other two have learning problems and display poor academic performance relative to same-age peers. There was no association noted between age at diagnosis and ultimate loss of IQ points. This prospective study suggests that children who receive a second course of cranial irradiation for treatment of CNS relapse are at high risk for significant and progressive intellectual loss. PMID- 2309980 TI - Chelation therapy and cardiac status in older patients with thalassemia major. AB - Cardiac dysfunction is the most common cause of death in patients with homozygous beta-thalassemia. We studied a group of 10 older patients (mean age 17.5 years) with and without preexisting cardiac dysfunction who had begun chelation therapy on the average of 10 years after regular transfusions were initiated. Over the 4 year study period, two patients were noncompliant with deferoxamine therapy. Their clinical status and cardiac function deteriorated, and both died with evidence of arrhythmia and congestive heart failure. The remaining eight patients were compliant. Despite a drop in mean serum ferritin from 3,814 +/- 577 (SE) ng/ml to 1,056 +/- 146 ng/ml (p less than 0.01), two patients with preexisting cardiac problems and one patient without preexisting heart disease developed further abnormalities. Of the three patients whose status declined, one ultimately improved with alternative chelation therapy. These data suggest that for a few older patients, improvement or stabilization of cardiac status may not be achieved with improved compliance and reduced serum ferritin levels. For these patients, new approaches appear to be warranted. On the other hand, we have demonstrated that in most cases, older patients who began chelation therapy years after transfusions began have benefited from compliance with standard subcutaneous deferoxamine regimens. PMID- 2309981 TI - Childhood myelodysplasia: suggested classification as myelodysplastic syndromes based on laboratory and clinical findings. AB - Fourteen children with a primary myelodysplastic syndrome (MDS) were seen at this center over a 10-year period. Six of the patients, including two pairs of siblings, had a monosomy 7 population in their bone marrow. Seven patients had the clinical and laboratory features of "juvenile chronic myeloid leukemia." Three patients could be considered to have either the monosomy 7 syndrome or "juvenile chronic myeloid leukemia," indicating that these two entities are not mutually exclusive. All patients fulfilled the French-American-British (FAB) criteria for a myelodysplastic syndrome. Clonal chromosomal abnormalities were detected in 13 of the 14 patients, and consistently involved either monosomy 7, multiple abnormalities, and/or multiple clones. Hematopoietic progenitor assays of blood and marrow samples obtained from most patients showed abnormal progenitor frequencies, or differentiation patterns in culture (or both), often affecting the erythroid as well as the granulopoietic lineages. In particular, granulopoietic progenitors from four to six patients in the "juvenile chronic myeloid leukemia" category generated predominantly abnormal appearing macrophage colonies. Clinical outcomes were poor with rapid transformation to acute myeloid leukemia in most patients. All treated patients responded poorly to conventional chemotherapy, although in two cases remission was achieved with intensive therapy and allogeneic bone marrow transplantation. Childhood myelodysplasia includes a group of diseases that are clinically heterogeneous, and current terminology is confused and inconsistent. Until a better understanding of the biologic and molecular basis of these diseases is obtained, it is proposed that the use of the FAB categories developed for adult MDS might help to improve diagnostic precision and therapeutic comparisons. PMID- 2309982 TI - Pulmonary hypertension and Gaucher's disease: logical association or mere coincidence? AB - A 17-year-old boy with Gaucher's disease died suddenly 2 days after femoral osteotomy. At autopsy, in addition to extensive infiltrates of Gaucher cells in the cirrhotic liver, lymph nodes, and bone marrow, there were high-grade pulmonary arterial hypertensive changes but virtually no Gaucher cells in the lung. Although previous reports have stressed lung infiltrates with capillary plugging by Gaucher cells as important in the pathogenesis of pulmonary hypertension, the present case raises the question of a different mechanism- possibly a circulating vasoactive substance that bypasses the diseased liver. PMID- 2309983 TI - Aluminum-induced microcytosis in a child with moderate renal insufficiency. AB - A child with moderate renal failure, on high doses of aluminum compounds for treatment for hyperphosphatasemia, presented with unexplained microcytosis. The patient also had psychomotor delay. On discontinuation of aluminum, microcytosis reversed in 2 months. Four months later, psychomotor development improved. Children with renal failure, on aluminum supplementation, should be carefully monitored for toxicity. Microcytosis may be a clue to aluminum toxicity in such patients. PMID- 2309984 TI - Pediatric oncology in the Czech lands: past and present. PMID- 2309985 TI - Growth of pediatric hematology/oncology in India. PMID- 2309986 TI - Evaluation of a capsulated hydrophilic carrier polymer (the ImmunoCAP) for measurement of specific IgE antibodies. AB - The Pharmacia CAP System is a new assay for serum specific IgE, utilising a solid phase capable of binding more antigen than conventional systems. The CAP System has been evaluated in 69 consecutive patients referred to one allergy clinic in relation to skin prick test (SPT), radioallergosorbent test (Phadebas RAST) and specific allergy diagnosis for five inhalant allergens, D.pteronyssinus, timothy grass pollen, cat epithelium/dander, Cladosporium and Alternaria. Good correlation was obtained between RAST and CAP for all allergens, e.g. r = 0.974 for D.pteronyssinus and r = 0.964 for grass pollen. When sensitivity and specificity were examined for both CAP and RAST versus SPT, CAP was usually found to be of greater sensitivity than RAST, and of similar or slightly lower specificity. SPT gave more positive reactions than either in vitro test, but CAP gave more positives than RAST. Twenty-two of 336 (6.6%) tests were CAP positive/RAST negative, whereas a negative CAP with a positive RAST occurred in only 2/336 (0.6%) tests. Of patients with any test (SPT or RAST or CAP) for specific IgE positive, up to 20-30% did not have clinical allergy, confirming the importance of the history in interpreting these tests. Our results suggest that, for the allergens tested, the Pharmacia CAP System is more sensitive than the RAST, identifying more positive tests and approximating more closely to the SPT. It offers the additional advantages of speed and efficiency. PMID- 2309987 TI - Comparative analysis of bovine extracts by immunoblotting and ELISA inhibition. Rabbit and human responses against cow epithelial and urine antigens. AB - Bovine epithelial and urine antigen extracts were compared using enzyme-linked immunosorbent (ELISA) inhibition assay and sodium-dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with immunoblotting. According to ELISA inhibition results, the two extracts share about 2% of their antigenic components. Urine derived antigens seem to be antigenically closer to serum proteins than epithelial antigens, as determined by rabbit immune sera. The IgG responses of allergic farmers against epithelial antigens were directed mainly against a protein of 20 kD, while non-allergic farmers had only very weak reactions. Generally, the IgG response against urinary antigens seemed to be more heterogeneous than against epithelial antigens. Almost all cow-allergic farmers reacted with a band at 20 kD in IgE immunoblotting against urinary and epithelial antigen while all non-allergic farmers showed negative results. PMID- 2309988 TI - Risk factors for sensitization to furred pets. AB - The risk factors for sensitization to pets was investigated in 169 male pupils. A recent or former contact with cats, dogs, and guinea pigs in own home was reported in 52 (30.8%), 42 (24.9%), and 20 (11.8%) study subjects, respectively. Clinically manifested allergy was found in two probands to cats and in two others to guinea pigs, three of them had formerly had pets and one proband with allergic rhinitis to cats had never had any pet. Sensitization to animals and aeroallergens was investigated with Phadezym-RAST. Only owners of cats had a higher incidence of cat sensitization than probands without direct contact (26.9% versus 10.3%, P less than 0.01). No statistically significant difference in sensitization to dogs and guinea pigs was found in groups with and without these pets. A strong correlation existed between sensitization to pets and other aeroallergens (house dust mite: P less than 0.025, birch pollen: P less than 0.0001, mugwort: P less than 0.0001, and grass pollens: P less than 0.0001). No association was found between sensitization to pets and smoking history, bronchial hyperreactivity to methacholine or radiological findings of the paranasal sinus. PMID- 2309989 TI - [Mixed venous versus central venous oxygen saturation in intensive medicine]. AB - Mixed venous oxygen saturation (SvO2) has been established as a useful guide in observing whole body oxygenation. Since SvO2 provides limited information about adequate tissue oxygenation for a specific organ, the usefulness of central venous saturation (ScvO2) as a guide was analysed, which is a less invasive parameter. In 19 ICU patients 44 pairs of blood samples were drawn from a separate central venous catheter and from the tip of an SG-catheter. The correlation of oxygen partial pressures was 0.687 and the correlation of the saturation reached 0.779. The calculation of venous admixture showed a correlation of 0.901. It is concluded that ScvO2 yields adequate information on the oxygen saturation of venous return. PMID- 2309990 TI - [Characteristics of the relative humidity and temperature in the inspiratory part of the Drager circle system and their influence on the function of the ciliary epithelium]. AB - Changes in relative humidity and temperature of the anaesthetic gases were measured in the inspiratory limb of the Drager circle system next to the carbon dioxide absorber in 29 patients requiring ENT surgery under general anaesthesia. Immediately following intubation and prior to extubation, nasal and tracheal cytologic samples were taken with a brush technique and ciliary beat frequency was determined. At a fresh gas flow of 6 l/min, relative humidity increased from 57.6 +/- 1.5 to 62.5 +/- 1.8% (p less than 0.05) after 110 minutes. Temperature increased continuously from 21.96 +/- 0.97 degrees C to 23.83 +/- 0.48 degrees C after 200 minutes. The number of vital ciliated cells in the tracheal samples decreased from 24.4% following induction of anaesthesia to 6% at the end of anaesthesia (p less than 0.05), and from 35.7% to 26.8% (p less than 0.05) in the nasal samples. Ciliary beat frequency remained unchanged at the end of anaesthesia as compared to control in tracheal as well as in nasal samples. It is concluded that the output of relative humidity and temperature in the circle system is not sufficient to prevent broncho-epithelial damage. Ciliary beat automaticity appears to behave according to an all or nothing principle. PMID- 2309991 TI - [Total intravenous anesthesia using propofol and alfentanil in comparison with balanced anesthesia in neurosurgery]. AB - Anaesthesia for neurosurgical patients should provide haemodynamic stability, reduce cerebral metabolism, preserve cerebral autoregulation, avoid increases of intracranial pressure and guarantee rapid recovery without respiratory depression. A commonly used Balanced Anaesthesia (BA, n = 20) (thiopental and fentanyl bolus induction and maintenance with repetition boluses of fentanyl and droperidol, thiopental infusion, and isoflurane in N2O/O2) was compared to Total Intravenous Anaesthesia (TIVA, n = 20) with propofol and alfentanil infusion. Pancuronium was employed for muscle relaxation in both groups. The TIVA evinced more haemodynamic stability during induction; notably, there was no increase in blood pressure after intubation, as seen in the BA group. Another advantage of TIVA is that it obviates the use of N2O. Quality of recovery after the procedure was determined by standardised psychometric tests. The time span between awakening of patients to orientation and concentration was significantly shorter in the TIVA group compared to the BA group. There was also a smaller deviation of these parameters in the TIVA group indicating a more predictable recovery. PMID- 2309992 TI - [Organ failure in patients with multiple trauma. The effect of early osteosynthesis of fractures on complications]. AB - The course of 225 multiple traumatized patients in our ICU with a mean age of 35 +/- 16.8 years, a mean ISS of 30 +/- 8.3 and an overall mortality of 18.2% was evaluated retrospectively. For comparable ISS the mortality was higher in patients over 65 years, and increased further with age. The most common causes of death were MOF (41.5%), severe head injury (34.1%), and acute respiratory failure (ARF) (19.5%). The mortality increased when two or more organ failures were present. 105 patients had fractures of the long bones; in 28 of these all fractures were stabilized primarily (during the first 24 hours). Organ failure was seen less frequently in these patients compared to those with secondary stabilization: ARF 10.7% vs. 51.9% (p less than 0.0004), acute renal failure 3.6% vs. 11.7%, liver failure 3.6% vs. 11.7%, sepsis 14.3% vs. 29.9%. Mortality was significantly lower in the patient with primarily stabilized fractures (7.1% vs. 24.7%, p less than 0.05). The study demonstrates that early stabilization of long bone fractures results in a more favourable course, and that this should be carried out whenever feasible. PMID- 2309993 TI - [Fresh gas flow and artificial respiration in anesthesia. Technical requirements for the adequate use of rebreathing systems]. AB - The majority of modern anaesthetic machines is designed for the rebreathing method. But frequently high fresh gas flows are employed, thus minimising the rebreathing fraction of expiratory gases. However, only by reducing the fresh gas flow substantially, the advantages of the rebreathing technique can be obtained. To evaluate the practicability of flow reduction, minimal flow anaesthesia was carried out with four different anaesthetic machines: AV 1 (Dragerwerk AG, Lubeck), ELSA (Gambro Engstrom AB, Bromma, Sweden), SULLA 808 V (Dragerwerk AG, Lubeck) und VIVOLEC (Hoyer Medizintechnik, Bremen). Fresh gas flow was reduced to 0.5 l/min after an initial phase of 15-20 min, during which the fresh gas flow was kept at a high level of 4.4 l/min. The minute volumes before and after fresh gas flow reduction were compared. The minute volume decreased markedly and significantly in the SULLA 808 group, whereas it remained nearly unchanged in the AV 1, the ELSA, and the VIVOLEC groups. The differences result from different modes of fresh gas delivery into the breathing circuit. If anaesthetic apparatus that maintain their tidal volume with different fresh gas flow rates are employed, rebreathing systems may be used judiciously by changing the fresh gas flow according to the individual uptake or any particular clinical requirement. PMID- 2309994 TI - [Computer-assisted documentation and performance data processing in the intensive care unit. Description of a custom development]. AB - Computer-aided documentation of medical and performance data processing seems to be imperative for every intensive-care unit in the future. It is the rational approach to deal with therapy-related information management as well as organizational and administrative tasks. This custom-made program is based on data collected from 3600 intensive-care patients. It serves 3 objectives: 1. documentation of relevant therapeutic data, 2. information exchange with other departments, 3. thorough analysis of topics related to intensive-care medicine. Based on a microsoft disc operating system, the programme contains not only the data base but also word processing and statistical capacities. Optional choice by menu guarantees easy handling and helps to create a high acceptance. PMID- 2309995 TI - [The effect of staged lavages in peritonitis on the vital functions]. AB - In 16 consecutive patients with diffuse peritonitis 93 staged lavages were undertaken. In a retrospective study the changes of some vital functions due to transport in the operating room and staged lavage were evaluated. 9 patients (56%) survived the diffuse peritonitis. The vital parameters showed no significant changes following staged lavages. Intraabdominal specimen cultures were positive in 62% of cases, showing no correlation of the underlying disease and mortality. Only an elevation of C-reactive protein and rise of thrombocyte count correlated significantly with the outcome of diffuse peritonitis. PMID- 2309996 TI - [Pharmacokinetic studies of a new 20% fat emulsion containing 70% medium-chain triglycerides]. AB - The aim of the study was to acquire basic knowledge on pharmacokinetic, metabolism and tolerance of a new 20% fatty emulsion with a 70% proportion of medium-chain triglycerides (MCT) and a 30% proportion of long-chain triglycerides (LCT) in the postoperative phase after a trauma of medium severity. - 12 female patients who had an elective rectal amputation and who needed parenteral nutrition postoperatively, were studied. The nutritional regime consisted of 4.8 g/kg/day of glucose and 1 g/kg/day of amino acids. On the second postoperative day the patients were given 0.06 g/kg body weight/h and on the third day 0.12 g/kg body weight/h of new 20% fatty emulsion during a time period of eight hours. Blood samples for the evaluation of triglycerides, free fatty acids, phospholipids, beta-hydroxybutyrate (beta-OHB), acetoacetate, cholesterol, glucose, pyruvate and lactate were taken before and after the fat application. Ketone were measured semiquantitatively. Side effects and complications were not observed. Simultaneously to the administrated triglycerides an increase in serum triglycerides was observed. After four hours fat emulsion was infused under steady state conditions. Under the graphically measured half-life of 17 minutes for the MCT/LCT emulsion, rapid and complete elimination could be seen after the infusion had been stopped. Simultaneously with the high clearance of the infused triglycerides, free fatty acids increased significantly in the plasma without reaching a plateau; 30 minutes after the fat application the laboratory results returned to the initial levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2309997 TI - [Nosocomial infections in surgical intensive medicine. Results of a 5-year prospective study]. AB - All the ICU patients were continuously studied during the first quarter of 5 consecutive years for infections according to a standard protocol. The investigators--the infection control officer and a well-trained infection control nurse--decided if the patient was infected by referring to medical and nursing record, temperature charts, laboratory and x-ray reports and, where necessary, by clinical examination. Definitions and criteria for infections comply with the CDC and the algorithms of the Senic Project. Only the first quarter of each year from 1980-1984 was analysed. The first quarter of 1980 was analysed retrospectively, the following years were examined prospectively. In 1984 a new ICU (ICU I) in addition to the old ICU (ICU II) was opened. The two ICUs differ in building construction but have similar patients, nursing staff and medical standards. The frequency of nosocomial infection was not affected by the different building constructions. The number of patients surveyed was 1009, 60% were males and 40% females. The average age was 45.5 years and the average period of stay about 4 days. 733 patients (72.6%) were intubated and artificially ventilated for 3 days. A fatal outcome resulted in 13.2% of all patients. 1129 nosocomial infections were registered in 311 patients, which means an infection rate of 32.8%. The most frequent nosocomial infections were those of the respiratory tract. Wound infections developed in 16.6%. The urinary tract was affected in 8.8%. Nosocomial septicaemias were observed in 8.7%. Catheter-associated infections were noticed in 6.7% of the patients. A fatal outcome resulted in 26% of the patients with nosocomial infections and in 6.9% of the non-infected patients, respectively. PMID- 2309998 TI - [Perioperative morbidity and mortality of geriatric patients. A retrospective study of 3905 cases]. AB - 3905 patients of more than 60 years of age who underwent surgical, urological, orthopaedic or opthalmologic interventions, were retrospectively investigated with respect to preoperative condition, intraoperative peculiarities and postoperative complications. Only 3.2% of the old patients (of more than 75 years of age), but 7.2% of elderly patients (between 60 and 74 years of age) had no coexisting disease. Preexisting diseases were myocardial (54.5%) and respiratory diseases (41.3%), hypertension (32.6%), dysrhythmia (30.8%) and diabetes mellitus (17.6%). From the old patients, 58.1% were classified into ASA physical status III to V but only 43.2% from the elderly patients. Peculiarities during anaesthesia and recovery period were (in total): dysrhythmia (8.3%), blood pressure decrease (5.9%) and increase (1.6%) that were significantly more often seen in old than in elderly patients whereas bleeding (4.5%) in the old was not different from the elderly. Independent of age, 11.6% of patients were monitored postoperatively on an intensive-care unit. 47.3% of all patients did not develop any postoperative complication. The incidence of postoperative cardiac, respiratory, central nervous, and lethal complications was not significantly higher in old than in elderly patients. However, the incidence of complications increased significantly with ASA physical status. Mortality of elderly and old patients after emergency interventions was 17.8% and 24.7% respectively and about 10 times that high as after elective surgery (2% in both groups.) PMID- 2309999 TI - [Nalbuphine as compared with pethidine for postoperative pain therapy]. AB - Nalbuphine is a new partly agonistic antagonistic opioid, that may offer some advantages especially in postoperative pain relief. We compared meperidine (1 mg kg-1) in 100 patients and nalbuphine (0.3 mg kg-1) in 70 patients, administering both agents intravenously after gynaecological operations. Standardised halothane anaesthesia without any opioid was used. After arrival in the recovery room, vigilance (sedation), quality and duration of pain relief were measured by different methods at four different times (0, 15, 30, and 60 minutes). Sedation was significantly more pronounced in the nalbuphine group, but no difference could be found in pain relief and duration between both groups. 6 patients of the n-group showed a short lasting wake-up reaction due to receptor antagonism. 36 patients had to be reinjected at the end of the first hour. We consider nalbuphine to be a safe opioid, however, the marked sedation should be taken into account. PMID- 2310000 TI - [Cricothyreotomy using the Quicktrach coniotomy instrument set]. AB - Percutaneous cricothyroidotomy may be a lifesaving procedure for airway obstruction, which cannot be relieved by endotracheal intubation and can be performed with specially designed instruments. A new device, the "Quicktrach", was evaluated by an anatomical preparation, flow and resistance measurements, and puncture of the cricothyroid membrane in 55 corpses. The size of the parts of the instrument (needle, plastic cannula, depth gauge) in relation to the size of the larynx is adequate, thus there is little likelihood of perforation of the posterior wall of the larynx. Resistance of the plastic cannula is sufficiently low to allow for adequate ventilation. The duration of time until the cannula is positioned properly in the trachea is significantly shorter, when an incision prior to the puncture is done (83 +/- 88 seconds without incision versus 35 +/- 41 seconds with incision; mean +/- SD). The "Quicktrach" is easy to apply even by inexperienced persons. The incidence of damage to the larynx (lesions including fractures of the thyroid, cricoid and 1. tracheal cartilage in 18%; soft tissue injury in 9%) is relatively high, however considering the live saving character of the procedure these numbers appear to be acceptable. Technical problems which occur with the use of the device are discussed and suggestions for improvement are made. PMID- 2310001 TI - [The pharmacokinetics of lidocaine in resuscitation conditions. Results of experimental studies on swine]. AB - To re-evaluate dosage requirements for i.v. and endobronchial (e.b.) lidocaine therapy under the conditions of cardiac arrest, we investigated the pharmacokinetics of lidocaine after i.v. and e.b. administration in an animal cardiopulmonary resuscitation (CPR) model. METHODS. We induced cardiac arrest by ventricular fibrillation in 16 normoventilated pigs under i.v. anesthesia. Resuscitation started after 3 min with resumed ventilation and internal cardiac compressions. Simultaneously, 8 animals received 10 micrograms epinephrine/kg and 2 mg lidocaine/kg via peripheral i.v. injection and another 8 received 100 micrograms epinephrine/kg and 2 mg lidocaine/kg via e.b. instillation. During CPR and the 1st hour of restored spontaneous circulation the ECG, heart rate, and mean arterial pressure were continuously recorded. Plasma concentrations of lidocaine were measured by gas chromatography in venous blood, which was collected automatically at intervals of 30 s. RESULTS. All animals were resuscitated successfully after 3.7 +/- 1.6 min (i.v.) and 3.8 +/- 1.1 min (e.b., means +/- SD). With no differences during CPR, the hemodynamic situation of the e.b. medicated animals was characterized by higher arterial pressures from 10-15 min and higher heart rates from 10-60 min of restored spontaneous circulation. Median maximum concentrations of lidocaine after i.v. (3.2 range 1.3-9.6 micrograms/ml) and e.b. administration (3.1 range 1.1-8.6) were measured after 5.5 min (range i.v. = 4-10 min, e.b. = 3-7 min). Mean concentrations within a therapeutic range of 2-5 micrograms/ml were reached after 2-3 min and remained within these limits for 20-25 min after both routes of administration. Individual lidocaine concentrations below the therapeutic level of 2 micrograms/ml were measured in one experiment after i.v. application and in three experiments after e.b. administration. The individual time concentration profiles were mathematically approximated using an open two - compartment model with first order absorption. The absorption half-life of e.b. lidocaine was 3.9 min, and mean bioavailability was 90%. Elimination pharmacokinetics of i.v. and e.b. lidocaine were nearly identical, with elimination half-lives of 25 min (e.b.) and 42 min (i.v.). Total body clearances were 401 ml/min (e.b.) and 362 ml/min (i.v.). CONCLUSION. An i.v. bolus of lidocaine during CPR should not exceed 2 mg/kg. During CPR without i.v. access the e.b. instillation of lidocaine can be recommended, but to ensure therapeutic concentrations a minimum dosage of 2 mg/kg is suggested. PMID- 2310002 TI - [Free intraabdominal air following an isolated gunshot injury to the trachea]. AB - This case report describes a 21-year-old male patient suffering from a close range suprajugular blank-cartridge injury, i.e. a gunshot injury without a projectile. On arrival at the hospital a cutaneous lesion of 5 mm in diameter was seen 2 cm above the jugular notch with traces of gunpowder in the surrounding skin. The cardiovascular status and spontaneous breathing were sufficient. On attempts to answer questions air was seen to escape from the lesion, indicating a tracheal defect. The patient was rapidly intubated and subjected to further diagnostic procedures. A chest X-ray film revealed bilateral pneumothoraces, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and marked subcutaneous emphysema of the chest and abdominal wall. After insertion of bilateral chest tubes, both lungs promptly reinflated and no air leakage could be demonstrated. As free intra-abdominal air has its source in a ruptured viscus in about 90% of cases, close attention was paid to possible abdominal symptoms. Contrast radiography and computer tomography (1st postoperative day) failed to demonstrate intestinal rupture. As there was no clinical evidence of peritonitis, exploratory laparotomy was not performed. Revision of the cervical lesion revealed locally extended destruction of tissues, including the pyramidal thyroid lobe and the anterior tracheal wall. After anastomosis of the trachea the endotracheal tube was left in place as an intraluminal splint for 8 days. Bronchoscopy at this time showed no evidence of tracheal stenosis and the patient was extubated. Two days later he left the hospital. The underlying pathophysiological mechanisms of free intra-abdominal air in the absence of gastrointestinal lesions are discussed and the literature is reviewed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310003 TI - [Anesthesia and intensive therapy of pregnant women with the HELLP syndrome]. AB - The HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) is a severe complication of pre-eclampsia with high risk for mother and fetus. During the last 40 months 27 parturients met the diagnostic criteria for HELLP syndrome in the University Hospital of Kiel (Tables 1-3). In 24 cases cesarean section was performed. Fetal mortality was 17.2%. In 13 women an uneventful clinical course resulted, all other patients developed complications: renal insufficiency (11 cases), disseminated intravascular coagulation (DIC) (4), intracerebral hemorrhage (1), cerebrovascular ischemia (1), eclamptic convulsions (3), reoperation due to intra- or extra-abdominal hemorrhage (4), severe blood loss ex vagina following spontaneous delivery (1), and liver rupture (1). Despite these severe complications no maternal death was observed. DIC, intrauterine death, and a rapid increase in liver enzymes are considered to be serious prognostic factors that could help to identify high-risk patients. The following recommendations for therapy of parturients suffering from HELLP syndrome are given: epidural anesthesia is not an appropriate method in HELLP syndrome because of the risk of epidural hemorrhage due to thrombopenia. At the present time general anesthesia seems to be the method of choice. Inhalation anesthetics such as halothane, enflurane, or isoflurane should probably be omitted in view of the preexisting hepatopathy. The high risk and the unpredictable postpartum course strongly indicate intensive care for parturients with HELLP syndrome. Antihypertensive, antieclamptic therapy and prophylactic measures to avoid renal insufficiency or hemorrhage (e.g. early substitution of erythrocytes, thrombocytes, and coagulation factors) deserve special attention. Co-operation between obstetrician and anesthesiologist is essential to obtain optimal therapy for these high-risk patients. PMID- 2310004 TI - [The double mask]. AB - While the consequences of occupational exposure to anesthetic gases and volatile agents on morbidity in operating room staff are controversial (survey in Swiss investigations show a distinct correlation with subjective complaints, e.g. tiredness and headache on the day of exposure (Table 1). In Sweden, rigorous control of occupational exposure to anesthetic gases has prompted development of various scavenging systems, among which the double mask (Fig. 1) is the latest and most advanced. During mask anesthesia, escaping anesthetic gases are evacuated at the point of leakage via a thin slot between a flexible silicone inner mask and a rigid plastic outer mask. A small plate in the mask produces turbulence in the otherwise laminar flow of anesthetic gases, thus reducing the speed of gas leakage. A silicone chamber is mounted on the mask and connected to a fan, requiring a flow of 35 m3/h for optimal function. This chamber does, however, also associate the system with two practical problems: the system with its evacuation tube is heavier to hold than conventional masks, and it is associated with increased dead-space that is only partly minimized by a modification of the Y-connector. While the handling is largely a matter of routine and the weight of the system is minimized when the evacuation tube is arranged to draw slightly upward, the increased dead space may reduce the practicality of the double mask in infants. PMID- 2310005 TI - [Determination of hemoglobin concentration using the hemoglobin azide method in traumatic emergencies]. AB - The present study examined the clinical practicability of a new hemoglobin measurement device based on a modified azide-methemoglobin reaction (HiN3 method) in trauma patients. The accuracy of the HiN3 method was compared to the internationally well accepted hemiglobincyanide method (HiCN method) in arterial, capillary, and venous blood samples. PATIENTS AND METHODS: 1. Comparison of the methods. In 62 trauma patients, hemoglobin measurements using the HiN3 method were compared to results obtained by the HiCN method. Blood samples were taken simultaneously from the same patient to evaluate each measurement procedure in arterial (group 1), capillary (group 2), and venous blood samples (group 3). 2. Accuracy. To evaluate the accuracy of both methods we compared two venous blood samples taken simultaneously from the same patient. 3. Reproducibility. For measurement of the reproducibility of the HiN3 method, the first two results of each three-time-measurement were compared. Statistical analysis of the results was performed using regression analysis. RESULTS: 1. Comparison of the methods. Comparing the results of hemoglobin measurements resulting from the HiN3 and HiCN methods, a strong correlation was found in arterial (Fig. 2), capillary (Fig. 3), and venous blood (Fig. 4). 2. Accuracy. The HiN3 method had an accuracy of +/- 1.47% and the HiCN method +/- 2.55%. 3. The reproducibility of the HiN3 method was +/- 1.25% (Fig. 5); however, one pair of samples did show a significantly different initial value (Hb 8.4 g/dl in I, but 10.4 g/dl in I and III). DISCUSSION: From our examinations in trauma patients, we can recommend this easy to handle device, particularly for acute diagnostic purposes in emergency patients and for trend evaluations both in the hospital and in the prehospital period for rapid and precise hemoglobin determinations. PMID- 2310006 TI - [Preoperative risk assessment: long-term electrocardiography for directed diagnosis of arrhythmias]. AB - The role of ambulatory electrocardiography for detection, confirmation, or exclusion of severe forms of arrhythmias was investigated in our preoperative anesthesia clinic. In a prospective study over a period of 21 months, 30 of 8935 preoperatively evaluated patients (0.3%) scheduled for noncardiac surgery were monitored by 24-h ambulatory ECG. Indications included common clinical reasons for ordering an ambulatory ECG and additional specific "anesthesiologic" indications: Syncopes, dizziness, or other manifestations possibly related to cardiac arrhythmias; Rhythm disturbances under antiarrhythmic drug therapy; Suspected paroxysms of supraventricular tachycardia; Q-T syndrome, R- on-T phenomenon; Insignificant rhythm disturbances in patients with significant cardiac disease such as cardiomyopathy, aortic stenosis, mitral valve prolapse; Rhythm disturbances in patients with poor general medical status; Recent myocarditis with arrhythmias; Previous known or suspected intraoperative cardiac complications; Suspected sick sinus syndrome. The mean age of the patients was 63.9 years; most (24/30) were classified as ASA III. In 4 patients with suspected bradycardic rhythm disturbances the ambulatory ECG proved a useful method for further decision-making compared to the routine resting ECG. According to the long-term ECG recordings 22 patients were classified as Lown IV. After effective antiarrhythmic therapy--usually with propafenon--none of these patients (n = 13) or those classified as Lown 0 to III (n = 8) showed intraoperative arrhythmias or other hemodynamic problems. In contrast, of the patients with complex rhythm disturbances refractory to antiarrhythmic drug therapy (n = 4) or those in whom emergency operations were performed without antiarrhythmic drug therapy (n = 2), 4 developed severe arrhythmias or other intraoperative hemodynamic problems. Two died on the 1st postoperative day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310007 TI - [The choice of the method of anesthesia as a risk factor in the femoral fracture near the hip joint in elderly patients]. AB - Between January 1983 and December 1988, 317 patients with fractures near the hip joint were operated upon. In a retrospective study we compared 180 patients with general anesthesia (AN) and 137 patients with spinal anesthesia (RA). The average age of patients with RA was 80.5 and with AN 79.8 years. The preoperative management was done by an internist. The operation followed at an average of 2.8 days (Tables 1, 2). All patients were placed into 3 risk groups, based on after preoperative cardiac and pulmonary risk scores, as modified by Goldman (Table 3). Spinal anesthesia was performed with 2 ml 4% hyperbaric mepivacaine (80 mg mepivacaine hydrochloride, 190 mg glucose monohydrate). The AN was induced with thiopental (3-5 mg/kg) and maintained with N2O and enflurane. Fentanyl (0.05-0.15 mg) was given for analgesia. The statistical examination was done using the chi square test (Fisher-exact or Pearson). The groups were compared for age, time of operation, and risk score (Table 4). The mortality in operations with protection of the femoral head (FP) (Ender pinnings, Bohler pinnings and dynamic hip screws) was significantly higher after RA (13.8%), than with AN (6.5%). In operations with hip prostheses (HP), the mortality for RA (19.0%) was also significantly higher then for AN (4.2%) (Fig. 1). The mortality in group I (4-20 points) was 1.7% in patients with AN (FP 1.4%, HP 2.1%) and 3.7% for RA (FP 4.1%, HP 0%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310008 TI - [The origin of non-emulsified fat during autotransfusions in elective hip surgery]. AB - In addition to hemodilution and preoperative blood donations, mechanical intraoperative autotransfusion (MAT) is an important method of preventing or minimizing the transfusion of homologous blood in operations with major blood loss. Using cell separators allows most of the problems of MAT to be solved, but the processed red cell concentrates of patients having hip joint replacement contain fat. Due to the high risk of fat embolism during bone surgery, as well as other circulatory problems, it is of interest whether the infusion of up to 15 ml of fat does not expose patients to an even higher risk. This study aimed to research the pathogenesis of fat embolism and possibly support one of the existing theories. METHODS. Semiquantitative oil measurement: in 45 cases with first insertion of hip joint prosthesis and 16 cases with change of prosthesis MAT was used intra- and postoperatively. For comparison, 10 patients with aortic aneurysm repair were checked for fat as well. In these cases MAT was only used intraoperatively. After the red cell concentrate was processed there was a time lag of 10 min to allow better sedimentation of fat. At the end of retransfusion 50 ml of blood were saved. They were then separated into 10-ml plastic tubes, centrifuged, and fat content was measured using a mm-scale. The results were transformed to ml by means of a previously determined calibration. Analogous to hematocrit values, it was thus possible to establish a lipocrit for these patients. In another 16 cases of hip surgery we carried out cholesterol/triglyceride investigations in red cell concentrates, and in 5 cases analysis of the fatty acids by gas chromatography was performed. RESULTS. The lack of an emulsifier causes biochemical analysis of cholesterol-triglyceride levels to be impossible. Therefore, triglycerides and cholesterol in MAT blood were below normal levels although a high quantity of fat could be seen in the blood. No oil was found in any of the patients in the vascular surgical group. There were 61 patients in the orthopedic group; no oil was found in 34.4%, we found 1-2 ml in 16.4%, and in 49.2% there was more than 2 ml of oil. With regard to age, sex, weight, height, and deviation from Broca index no significant difference in lipocrit could be seen. Differences in lipocrit were observed depending on the type of operation (i.e. new insertion/change of hip prosthesis), these were not significant possibly due to the small number of patients undergoing a change of prosthesis. The more MAT blood was transfused, the more significant were the rises in lipocrit level. The rinsing solution itself (1000 ml NaCl 0.9% with heparin 30,000 IU) does not influence the oil concentrations. Gas chromatography revealed that there was more than 40% oleic acid and 20% palmitic acid. Combined with linoleic acid, this comprised 4/5 of the total amount of oil (Table 3)... PMID- 2310009 TI - Protocol for liquid chromatography/mass spectrometry of glutathione conjugates using postcolumn solvent modification. AB - A novel protocol for thermospray liquid chromatography/mass spectrometry (LC/MS) analysis of mixtures of glutathione conjugates is reported. Solvent conditions for optimal high-performance liquid chromatography are not always the same as for optimal thermospray ionization mass spectrometry. Labile glutathione conjugates that give poor spectra in aqueous ammonium acetate yield more intense molecular ion signals with increased percentages of acetonitrile. Direct injection thermospray ionization using 30-60% acetonitrile in aqueous ammonium acetate produced protonated molecular ions for glutathione conjugates of menadione, styrene oxide, pentachlorophenyl methyl sulfone, chlorodinitrobenzene, and chlorambucil. Since, the high percentages of organic modifier needed for good molecular ion intensity preclude chromatographic separation of these polar compounds, successful graphic separation of these polar compounds, successful LC/MS was facilitated by postcolumn addition of organic modifiers to the mobile phase. This new methodology allowed excellent chromatographic separations and thermospray ionization mass spectra to be obtained for a mixture of haloalkane glutathione conjugates. Moreover, cleavage of the gamma-glutamyl-cysteine amide bond of glutathione results in class-characteristic fragment ions. Changes in the fragmentation pathways in spectra acquired with and without organic modifiers shed light on the importance of the desolvation process in obtaining good molecular ion sensitivity in thermospray. PMID- 2310010 TI - Simultaneous enhancement of separation selectivity and solvent strength in reversed-phase liquid chromatography using micelles in hydro-organic solvents. AB - The role of micelles and organic solvents as the modifiers of the aqueous mobile phase in reversed-phase liquid chromatography (RPLC) in controlling retention and selectivity is discussed. Elution strength increases in RPLC with an increase in organic solvent or micelle concentration. Simultaneous enhancement of separation selectivity with elution strength in the hybrid eluents of water-organic solvent micelles was observed. This selectivity enhancement occurs systematically, i.e. peak separation increases monotonically with volume fraction of organic solvent added to micellar eluent, and is observed for a large number of ionic and nonionic compounds with different functional groups and for two surfactants (anionic and cationic). For two test mixtures, 13 amino acids/peptides and 15 phenols, it is shown that a better separation and shorter analysis time are observed at stronger hybrid eluents. This selectivity enhancement can be attributed to the competing partitioning equilibria in micellar LC systems and/or to the unique characteristics of micelles to compartmentalize solutes and organic solvents. PMID- 2310011 TI - Effect of wet decomposition methods on the determination of cobalt, copper, selenium, and zinc in biological samples using electrophoresis. AB - A method combining radiotracer techniques with paper electrophoresis to investigate the optimal decomposition conditions for cobalt, copper, selenium, and zinc in rat liver samples is described. After oral and intraperitoneal administration of the respective nuclides of 60Co, 64Cu, 75Se, and 65Zn solutions, the livers of the tested rats are removed and decomposed with a nitric and sulfuric acid mixture. The completeness of decomposition is investigated by measuring the respective radionuclide-containing species in the decomposed samples by electrophoretic analysis. The results indicate that the Co- and Se containing liver samples are more easily decomposed than those containing Cu and Zn under the specific conditions. The same decomposition effects are observed for ingested radioisotopes as for intraperitoneally injected ones. The possible connection of decomposition with the analytical error is discussed. PMID- 2310012 TI - Laser-excited atomic fluorescence in a pulsed hollow-cathode glow discharge. AB - A pulsed glow discharge with low background noise is evaluated as an atom reservoir for laser-induced atomic fluorescence spectroscopy. Aqueous solutions are dried in graphite electrodes that are used as disposable hollow cathodes. Atomic vapor is produced in a flowing-gas glow discharge with a water-cooled cathode holder. A dye laser triggers a switching circuit that pulses that glow discharge, and fluorescence measurements are made 100 microseconds after the discharge is extinguished. The atomic population is large during this dark period, while the background emission is negligible. Linear calibration curves are obtained by nonresonance fluorescence for two elements, Pb and Ir. The detection limits for Pb are 100 pg/mL and 500 fg, and for Ir are 6 ng/mL and 20 pg. The experimental detection limit for Pb is compared to the intrinsic detection limit. PMID- 2310013 TI - Automated instrumentation for comprehensive two-dimensional high-performance liquid chromatography of proteins. AB - A comprehensive two-dimensional (2-D) liquid chromatographic separation system is presented. The system uses a microbore cation exchange column, operated under gradient conditions, as the first dimension separation. Effluent from this first column alternately fills one of two loops on a computer-controlled eight-port valve. A second pump then forces loop material onto a second column, a size exclusion column. UV detection is used, and the system is applied to the separation of protein standards and serum proteins. The 2-D system has a higher resolving power and peak capacity than either of the two columns used alone. The entire first column effluent is analyzed on the second column in virtually the same time it takes to complete the first column separation, without the use of stopped flow methods. The entire system is automated and operated under computer control. Three-dimensional (3-D) data representation provides a means of viewing peak profiles in either separation dimension and contour mapping of the 3-D data provides a more reliable means of peak identification from run to run than that provided by single-column elution times. PMID- 2310014 TI - Bayesian versus Fourier spectral analysis of ion cyclotron resonance time-domain signals. AB - The frequency-domain spectrum obtained by Fourier transformation (FT) of a time domain signal is accurate only for a continuous noiseless time-domain signal of infinite duration. For discrete noisy truncated time-domain signals, non-FT (e.g., Bayesian analysis) methods may provide more accurate spectral estimates of time-domain signal frequencies, relaxation time(s), and relative abundances. In this paper, we show that Bayesian analysis of simulated and experimental ion cyclotron resonance (ICR) time-domain noisy signals can produce a spectrum with mass accuracy improved by a factor of 10 or more over that obtained from a magnitude-mode discrete fast Fourier transform (FFT) spectrum. Moreover, Bayesian analysis offers the useful advantage that it automatically estimates the precision of its iteratively determined spectral parameters. The main disadvantage of Bayesian analysis is its lengthy computation time compared to that of FFT (hours vs seconds on the same hardware for approximately 4K time domain data points); the Bayesian computation time increases rapidly with the number of spectral peaks and (less rapidly) with the number of time-domain data points. Bayesian analysis should thus prove useful for those FT/ICR applications involving relatively few data points and/or requiring high mass accuracy. PMID- 2310015 TI - Reversing enantioselectivity in capillary gas chromatography with polar and nonpolar cyclodextrin derivative phases. PMID- 2310016 TI - Binding studies using ion-selective electrodes. Examination of the picrate albumin interaction as a model system. AB - We are studying the binding of ligands to macromolecules by using ligand ion selective electrodes as transducers. The picrate-bovine albumin interaction is examined in detail as a model system. A picrate ion selective electrode is used to monitor the free picrate concentration directly in the presence of albumin and bound ligand. The binding parameters are estimated and the effect of protein concentration, ionic strength, pH, and temperature is studied. The experimental data are interpreted with a specially designed computer program that performs nonlinear least-squares fitting of the generalized Scatchard model with an infinite number of classes of binding sites directly to the raw potentiometric data. The binding parameters (binding constant and maximum number of ligands that can be bound), the nonspecific binding as well as their standard deviations are estimated by this program. The principles described can be used for the potentiometric study of any ligand-binder interaction. PMID- 2310017 TI - Optimization of multienzyme flow reactors for determination of acetylcholine. AB - Immobilized enzyme reactors have been used with high-performance liquid chromatography (HPLC) and electrochemical detection to detect acetylcholine and choline in brain tissue samples. Acetylcholine and choline eluting from the LC column are introduced into a reactor containing immobilized acetylcholinesterase, which hydrolyzes acetylcholine to choline. The product is converted by a second enzyme, choline oxidase, to hydrogen peroxide, which is determined amperometrically. Several novel immobilization techniques including immobilization through enzyme-specific antibodies were used to immobilize these enzymes to retain maximum activity. Improved detection limits were observed when the enzymes were immobilized through the avidin-biotin linkage. Better sensitivity and detection limit were obtained when both enzymes were immobilized together on the same support through the avidin-biotin linkage than when they were separately immobilized and used in two columns. The postcolumn system was applied to brain tissue extracts. PMID- 2310018 TI - How far can we go with compartmental models? PMID- 2310019 TI - The relationship of age to the pharmacokinetics of early drug distribution: the concurrent disposition of thiopental and indocyanine green. AB - The optimal dose of thiopental depends both on its initial distribution kinetics, which determine its concentrations at sites of action after iv administration, and on its pharmacodynamics. The disposition of concomitantly administered thiopental and indocyanine green (ICG), a marker of intravascular space, was determined in 21 patients, aged 20-80 yr, to determine the pharmacokinetic basis of increased reactivity of the elderly to thiopental. Data obtained from frequent early arterial blood samples and the simultaneous modelling of thiopental disposition with that of ICG allow a rigorous description of early drug distribution. Their disposition is described by a two-compartment ICG model and a four-compartment thiopental model that have a common central volume, V1, the central blood pool. ICG distributes, by intravascular mixing, from V1 to a peripheral blood volume that is a subset of a rapidly equilibrating (fast) peripheral thiopental compartment; elimination clearance of both drugs is modelled from these peripheral compartments. In contrast to the results of others, the results of this study demonstrate that V1 does not decrease with increasing age. The only pharmacokinetic variable that changed with age is the intercompartmental clearance (Cl21) from V1 to the rapidly equilibrating peripheral volume, V2, which decreased 35% between the ages of 20-80 yr. The authors suggest that V1 and the intercompartmental clearances may be used together to explain smaller dose requirements in individuals with increased reactivity to thiopental; such an analysis does not predict that dose adjustments should be made on the basis of age alone. PMID- 2310020 TI - Population pharmacokinetics and pharmacodynamics of thiopental: the effect of age revisited. AB - The authors have previously attributed the mechanism for the 50-67% decrease in the required dose of thiopental for induction of anesthesia in aged human patients to a decrease in the initial distribution volume for thiopental. Using a larger group of patients and volunteers studied in the laboratory, the authors have re-examined thiopental pharmacokinetics and EEG pharmacodynamics relative to age. A population data analysis approach (NONMEM), using a three-compartment model, was used to analyze bolus and rapid iv infusion thiopental serum concentration versus time data from 64 subjects. A one-compartment model was also used on the first 10 min of serum concentration data to focus only on the initial distribution phase. The population pharmacokinetic analysis demonstrated that when thiopental is administered via an iv bolus injection, traditional pharmacokinetic models limit the accurate characterization of thiopental distribution phenomena. Using the rapid iv infusion data, the pharmacokinetic mechanism for the decreased thiopental dose requirement in the elderly was a decreased rapid intercompartment clearance. Thiopental distribution from the central compartment of the three-compartment model to the rapidly equilibrating compartment (rapid intercompartment clearance) decreased 27% between the ages of 35-80 yr and decreased 34% in the one-compartment analysis. EEG spectral edge versus time data from 37 subjects was analyzed with a semiparametric modelling approach to remove the disequilibrium between thiopental serum concentration and the spectral edge. A population data analysis (NONMEM) was performed with several pharmacodynamic models. There was no age-related change in brain responsiveness or pharmacodynamics when the spectral edge is used as a measure of drug effect. PMID- 2310021 TI - Binding of thiopental in neonatal serum. AB - Protein binding of thiopental was studied in 21 samples of neonatal serum (from placental blood) and compared with protein binding in ten healthy volunteers. These infants ranged between 32 and 43 weeks of gestational age (mean, 37.7 weeks) and the adult age range was from 27 to 54 years (mean, 35.4 years). Because the unbound fraction of the drug is responsible for its pharmacologic effect, a marked difference in the protein binding between neonates and adults may be relevant to the clinician. Blood obtained from freshly delivered placentas or from adult volunteers was allowed to clot and the serum separated from the sample. A portion of the serum was sent for protein and bilirubin analysis and the remainder retained for study. This latter serum was combined with four concentrations of thiopental. These specimens were then ultrafiltered and the amount of thiopental in the ultrafiltrate (unbound) compared with the prefiltered amount (total), as measured by reverse-phase high-performance liquid chromatography. The binding studies were repeated at pH 7.2, 7.4, and 7.6 in both the adult and neonatal serum. Total protein and albumin are significantly less in neonatal serum, whereas bilirubin (total and direct) is significantly higher in neonatal serum than in adult serum (P less than 0.01). Neonatal serum was associated with significantly more unbound thiopental than adult serum at all levels of pH studied (P less than 0.005). Increasing the pH resulted in less free drug in both groups, but this reached statistical significance only in the adult group (P less than 0.025). Drug concentration had no effect on binding in the range examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310022 TI - Preoperative and intraoperative echocardiography to detect right-to-left shunt in patients undergoing neurosurgical procedures in the sitting position. AB - In patients undergoing neurosurgical procedures at high risk for venous air embolism (VAE), the presence of a right-to-left shunt adds an additional risk for paradoxical air embolism (PAE). Although this is a rare complication, it can have devastating results. The most common form of right-to-left shunt is a patient foramen ovale (PFO), which can be detected by contrast echocardiography. This study evaluates the efficacy of preoperative precordial and intraoperative transesophageal echocardiography (TEE) to detect right-to-left shunting in patients undergoing neurosurgical procedures while in the sitting position. In 101 patients precordial contrast echocardiography was performed prior to surgery. The Valsalva maneuver was utilized as a provocative maneuver to facilitate demonstration of right-to-left shunting. Fifty-one of these patients also had intraoperative TEE monitoring. Right-to-left shunting was demonstrated in only six of the 101 patients examined. Of these, four were detected by TEE. This is less than the expected incidence based on the known incidence of PFO in the general population. The usefulness of preoperative ECHO as a screening test for PFO in patients undergoing neurosurgical procedures is limited, but when a PFO is found, valuable information is acquired to help manage these patients. PMID- 2310023 TI - The position and the state of the larynx during general anesthesia and muscle paralysis. AB - Based on a chance observation in two patients in whom the larynges could be visualized during direct laryngoscopy using topical anesthesia but not after general anesthesia and muscle paralysis, the authors postulated that there will be a shift in the position of the larynx with the onset of general anesthesia and muscle paralysis. To verify this the authors measured the position of larynx in lateral radiographs of necks taken in human volunteers when they were awake, and after induction of general anesthesia and muscle paralysis. The authors found that the hyoid bone and epiglottis were shifted anteriorly and the supraglottic region or the vestibule of the larynx was enlarged with the onset of general anesthesia and muscle paralysis. In addition, the larynx was also stretched longitudinally with wide separation of the vestibular and vocal folds. The authors conclude that consciousness is associated with tonic muscular activity that folds the larynx and partially closes it and that onset of general anesthesia and muscle paralysis opens the larynx wider and shifts it anteriorly, which might make visualization of the larynx during direct laryngoscopy difficult in some patients. PMID- 2310024 TI - Influence of local anesthetic solution on postdural puncture headache. AB - A total of 2,511 patients who received spinal anesthesia for cesarean delivery were observed for the development of postdural puncture headache (PDPH); 804 patients received a mixture of tetracaine and procaine, 942 received bupivacaine glucose, and 765 received lidocaine-glucose. They were observed for the development of PDPH for a minimum of 72 h. PDPH occurred in 9.54% of patients who received lidocaine-glucose during the first 36 h compared with 7.64% of patients who received bupivacaine-glucose and 5.85% of patients who received tetracaine procaine. The differences between all groups was statistically significant. No differences were found in the percentage of patients who ultimately required epidural blood patch for relief of symptoms after 36 h. PMID- 2310025 TI - Chronic alcohol intake does not change thiopental anesthetic requirement, pharmacokinetics, or pharmacodynamics. AB - The anesthetic requirements of chronic alcoholics for induction of anesthesia with thiopental were investigated using an electroencephalographic (EEG) measure of thiopental's CNS drug effect and pharmacodynamic modeling to relate thiopental serum concentrations to drug effect. Eleven patients with a history of excessive alcohol intake were studied from an inpatient alcohol rehabilitation program and compared with nine control patients or volunteers who were social drinkers. The alcoholic population had consumed ethanol 9-17 days prior to the study. They had no evidence of acute intoxication or acute withdrawal at the time of the study. Five of the 11 alcoholic patients were restudied after 1 month of abstinence from alcohol consumption. Each study consisted of a thiopental infusion until EEG burst suppression (1-3 s of isoelectric signal) was achieved. Timed arterial and then venous blood samples were obtained for measurement of thiopental serum concentrations for up to 36 h. Pharmacokinetic differences between groups were analyzed using a three-compartment model. Power spectral analysis of the EEG allowed determination of spectral edge frequency. An inhibitory sigmoid Emax pharmacodynamic model combined with an effect compartment was used to analyze concentration-response relationships and to provide an estimate of brain sensitivity to thiopental in the study populations. The thiopental anesthetic dose requirement using the EEG was not different between alcoholics and nonalcoholics. The mean dose requirement (+/- SD) of alcoholics was 823 +/- 246 mg and the mean dose requirement of nonalcoholics was 733 +/- 218 mg. There were no differences in thiopental pharmacokinetic and pharmacodynamic parameters between alcoholics and nonalcoholics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310026 TI - Peripheral vascular effects of halothane and isoflurane in humans with an artificial heart. AB - The peripheral vascular effects of isoflurane and halothane were compared in five critically ill patients in whom a Jarvik-7 artificial heart had been implanted. The lungs of all patients were mechanically ventilated in the postoperative period and the patients were monitored with an arterial catheter and with catheters that had been surgically inserted into the right and left atria and into the pulmonary artery. Norepinephrine and epinephrine plasma concentrations were measured using a radioenzymatic assay. The Jarvik-7 settings were modified to render the artificial heart "preload independent" and to maintain cardiac output constant. Each patient was anesthetized twice using halothane and isoflurane at two different MAC levels, 1 and 1.5 (Datex vapour analyzer), with the interval between each anesthetic ranging from 12 to 26 h. Both anesthetics significantly decreased mean arterial pressure (from 100 +/- 11 mmHg to 66 +/- 13 mmHg for halothane and from 102 +/- 17 mmHg to 48 +/- 11 mmHg for isoflurane; mean +/- SD) and systemic vascular resistance index (from 27 +/- 11 Wood units/m2 to 18 +/- 6 Wood units/m2 for halothane and from 30 +/- 6 Wood units/m2 to 13 +/- 3 Wood units/m2 for isoflurane; mean +/- SD), but with isoflurane to a significantly greater extent than with halothane (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310027 TI - The laryngeal mask airway in pediatric radiotherapy. AB - The use of the laryngeal mask airway, a new form of airway, is described in infants and young children receiving radiotherapy under general anesthesia. The laryngeal mask airway consists of a tube, at the distal end of which is attached an elliptically shaped cuff resembling a miniature face mask. The laryngeal mask is inserted blindly into the pharynx, and its cuff forms a low pressure seal around the larynx through which the patient can breathe spontaneously. No complications occurred during use of the laryngeal mask in 25 children who received 312 anesthetics. This experience suggests that the laryngeal mask airway has a valuable role in this situation and may contribute to the safety of anesthesia. PMID- 2310028 TI - Patient variables and the subarachnoid spread of hyperbaric bupivacaine in the term parturient. AB - To determine if age, height, weight, body mass index, or vertebral column length significantly influence the distribution of sensory analgesia or anesthesia after subarachnoid injection of hyperbaric bupivacaine, 52 women presenting for cesarean section were studied. All received 15 mg hyperbaric bupivacaine via subarachnoid injection at L-2 or L-3. Fifteen minutes after injection, while the women lay supine on a horizontal operating table, the maximum cephalad extent of sensory analgesia (loss of sensation of sharpness to pin prick) and anesthesia (loss of sensation of light touch) was determined. Age (20-42 yr), height (146.9 174.0 cm), weight (55.5-136.4 kg), body mass index (19.2-50.0 kg/m2), and vertebral column length (49.6-67.0 cm) did not correlate with the spread of sensory blockade. In conclusion, in parturients of age, height, weight, body mass index, and vertebral column length within the aforementioned ranges, it is not necessary to vary the dose of injected hyperbaric bupivacaine with changes in any of the patient variables studied. PMID- 2310029 TI - Uptake and distribution of lidocaine in fetal lambs. AB - The fetal uptake of lidocaine was measured continually and quantitatively during and after a constant rate intravenous (iv) maternal infusion into five chronically prepared pregnant ewes. Lidocaine, 6 mg/kg (base), was infused at a constant rate for 1 h and measurements continued to 5 h. Rate of fetal uptake was determined from the product of the umbilical venous (UV) and fetal aortic (FA) concentration difference and umbilical blood flow (Qu). Total fetal uptake was determined by integrating fetal uptake rate with respect to time. Maternal and fetal protein binding was determined, and its effect on fetal blood concentrations was evaluated. Mean total fetal uptake as it related to time and infused dose increased linearly (r = 0.998, P less than 0.001) with a constant, weight-normalized fetal-maternal dose fraction of 0.45 during the infusion. Despite rapidly declining blood concentrations after the infusion, uptake increased an additional 17%. The sevenfold variation in uptake appeared to be inversely related to the biodegradation rate of lidocaine. Fetal-maternal concentration ratios (F/M) increased during declining blood concentrations. Protein binding determinations for maternal and fetal blood were 43.6 +/- 2.48% and 26.9 +/- 1.59%, respectively. These values were used to calculate the F/M in conjunction with the maternal and fetal pH. At maternal-fetal equilibrium the calculated F/M, 1.0 +/- 0.05, closely approximated the observed, 1.0 +/- 0.03. Variations in lidocaine concentrations among the vital organs 4 h after the infusion were small, but high concentrations of metabolites were found in the lungs and kidneys. The results challenge the validity of placental transfer estimates commonly based on the F/M and umbilical cord blood concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310030 TI - Effect of increased intracranial pressure on regional hypoxic pulmonary vasoconstriction. AB - The effects of increased intracranial pressure (ICP) and increased cardiac output (QT) on the pulmonary vascular response to regional alveolar hypoxia were compared in pentobarbital-anesthetized, closed-chested dogs. A bronchial divider was inserted, the right lung (RL) was continuously ventilated with 100% O2, and the left lung (LL) was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Sulfur hexafluoride (SF6) was used to measure differential lung blood flow and the multiple inert gas technique assessed gas exchange. The response to LL alveolar hypoxia (hypoxic pulmonary vasoconstriction, HPV) was studied in each animal prior to, during, and after the ICP was increased by infusing mock cerebrospinal fluid (CSF) into a lateral ventricle so that cerebral perfusion pressure was 25 mmHg. During both control periods, QT was randomly altered by opening (high QT) or closing (normal QT) two arteriovenous fistulas. Increasing ICP significantly increased QT (P less than 0.01), pulmonary artery pressure (PAP) (P less than 0.05), and mixed venous oxygen tension (PVO2) (P less than 0.05), compared with normal QT controls. Opening the arteriovenous fistulas achieved similar increases in QT (P less than 0.01), PAP (P less than 0.05), and PVO2 (P less than 0.05). The percentage of blood flow to the LL (QL/QT%) during hyperoxia was 43.9 +/- 0.8% (mean +/- SE) and did not vary with manipulation of QT or ICP. QL/QT% during LL hypoxia was significantly increased by both increased ICP (24.6 +/- 3.5%) and high QT (23.1 +/- 1.0%) compared with normal QT (16.8 +/- 2.1) controls (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310031 TI - Comparison of anticholinesterases and their effects on acetylcholine-activated ion channels. AB - Single-channel recording techniques have been used to examine interactions between anticholinesterases and ion channels activated by acetylcholine. Single channel currents activated by 200 nM acetylcholine were recorded from cell attached patches of BC3H1 mouse tumor cells grown in culture. Channels were recorded in the absence and presence of edrophonium (1-20 microM), neostigmine (2 20 microM), or pyridostigmine (10-200 microM). All three drugs shortened channel open time but did not alter single-channel current amplitude. Effects on channel open time were not secondary to inhibition of cholinesterase but appeared to involve direct interactions between anticholinesterase drugs and acetylcholine activated channels. Drug concentrations calculated to reduce the time constant of open time distributions by 50% were 3.8 microM edrophonium, 4.6 microM neostigmine, or 97 microM pyridostigmine. Channel open time was decreased by edrophonium at concentrations comparable to those occurring during reversal of neuromuscular block, but it was reduced by neostigmine and pyridostigmine only at levels higher than those encountered clinically. Differences in interactions between anticholinesterases and acetylcholine-activated channels at the end plate may possibly account for some of the clinical differences between these drugs. PMID- 2310032 TI - The effects of volatile anesthetics on Ca++ mobilization in rat hepatocytes. AB - This study provides direct evidence that in hepatocytes, intracellular Ca++ is released from internal stores by halothane, enflurane, and isoflurane. Hepatocytes isolated from rat livers were used fresh or treated with saponin and then incubated in 45Ca++ media. The uptake of 45Ca++ by hepatocytes was maximal following 13-16 min of incubation (untreated or saponin-treated) and the effects of various agents on the release of 45Ca++ was studied following maximal loading. The agents used included halothane, enflurane, isoflurane, and several putative intracellular second messengers. The anesthetics, to various degrees, all stimulated a significant release of 45Ca++ from internal stores at concentrations that were at or less than clinical concentrations. The release of intracellular 45Ca++ by each of the anesthetic agents was dose-dependent with halothane and enflurane being equally potent at concentrations equivalent to 1 MAC exposure. The halothane-induced release was only somewhat suppressed by preincubation in either 2 mM LaCL3 or 10 microM dantrolene, both suggested Ca++ channel blockers. Transient increases in intracellular Ca++ regulates a number of enzyme systems, including glycogenolysis, while prolonged elevation in Ca++ concentrations have been implicated in the mechanism of hepatotoxicity. PMID- 2310033 TI - Oxygen delivery and consumption during hypothermia and rewarming in the dog. AB - Changes in oxygen consumption (VO2) and oxygen delivery (DO2) were compared in three groups of paralyzed, sedated dogs: 1) a group (n = 5) cooled to 29 degrees C and immediately rewarmed to 37 degrees C; 2) a group (n = 5) cooled to and maintained at 29 degrees C for 24 h, and then rewarmed; and 3) a group (n = 5) maintained at 37 degrees C for 24 h. During the cooling phase, in both the acute and prolonged hypothermia animals, VO2 and DO2 decreased significantly from control values (P less than 0.05). The decrease in DO2 occurred as a result of a similar decrease in cardiac index (CI; P less than 0.05) that was associated with a significant increase in systemic vascular resistance index (SVRI; P less than 0.05). Arteriovenous oxygen content difference (C(a-v)O2), O2 extraction ratio, mixed venous oxygen tension (PVO2), pH, and base deficit (BD) were not different from control values even during prolonged hypothermia. Normothermic control dogs also demonstrated a significant decrease in CI (P less than 0.05) at 24 h. Surface rewarming increased VO2 back to control values in the acute hypothermia group and to values above control (P less than 0.05) in the prolonged hypothermia group. DO2 remained below control in both groups, resulting in a significant increase in O2 extraction (P less than 0.05) and a decrease in PVO2 (P less than 0.05) in the prolonged hypothermia animals. Following rewarming administration of sodium nitroprusside returned DO2, CI, and SVRI to control values but did not increase VO2. All animals survived the study without need for inotropic support.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310034 TI - Myocardial ischemia in a canine model of pulmonary hypertension and right coronary artery stenosis. AB - This study was performed to study the effects of acute pulmonary embolization (injection of autologous muscle) on global and regional (ultrasonic dimension technique) right ventricular (RV) performance, coronary hemodynamics (electromagnetic flow probes), and gas exchange during underlying critical stenosis (cuff occluder) of the right coronary artery (RCA) in eight open-chest dogs. Resting coronary blood flow (CBF) and regional myocardial performance remained unaffected by the induction of RCA stenosis. Following embolization pulmonary artery (PA) pressure, pulmonary vascular resistance, end-diastolic dimensions and pressure increased, and PA flow, stroke volume (SV), and aortic pressure (AoP) decreased (P less than 0.05). There was a marked decline (60%) in CBF accompanied by severe myocardial dysfunction suggestive of ischemia (akinesis, systolic lengthening, postsystolic shortening) in the area supplied by the stenosed RCA. Gas exchange, lung compliance, and pH worsened. Release of the RCA constriction led to a fourfold increase in CBF, return of PA flow, SV, and AoP to baseline values, and disappearance of regional myocardial dysfunction despite continued pulmonary hypertension. These data indicate that RV function may deteriorate in response to even small increases in afterload if coronary vascular reserve is absent and aortic pressure is allowed to decrease. PMID- 2310035 TI - Effects of halothane on human and rat hepatocyte cultures. AB - The aim of this study was to investigate direct cytotoxicity to human and rat hepatocytes in primary culture from halothane and compare it with that of isoflurane, which is known to be minimally metabolized and less toxic in vivo. Both human and rat parenchymal cells were isolated by the two-step collagenase perfusion method and after attachment to plastic were incubated with either volatile anesthetic for 24 h. All the cultures were maintained in 20% O2 condition and were not induced prior to anesthetic treatment. Temperature, atmosphere conditions, and anesthetic concentrations were kept constant during the study period. Evaluation of cytotoxicity was based on morphologic, biologic (determination of both extracellular and intracellular lactate dehydrogenase activity), and metabolic (protein synthesis and secretion) end points. Protein synthesis and secretion rates were found to be the most sensitive parameters in hepatocyte cultures from both species. Protein synthesis was inhibited by 18% and protein secretion by 50% in the presence of 1 and 1.25 mM halothane, respectively, in human cell cultures (P less than 0.05). With 1.25 mM halothane intracellular lactate dehydrogenase was also decreased; lactate dehydrogenase leakage and morphologic alterations were detected only beyond 5 mM halothane. By contrast, in rat hepatocyte cultures protein secretion was inhibited by 26% and protein synthesis by 20% in the presence of 0.1 and 0.75 mM halothane, respectively, whereas morphologic alterations and a 37% lactate dehydrogenase leakage increase were observed with the concentration of 1 mM (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310036 TI - Fentanyl is devoid of major effects on coronary vasoreactivity and myocardial metabolism in experimental animals. AB - Experiments were designed to determine the effects of fentanyl on coronary vascular tone and energetic state of the heart. Both arterial and arteriolar responses were assessed; particular attention was directed to epicardial vessels. Four experimental methods and three animal species were used. Isolated canine coronary artery rings with and without endothelium were suspended in organ chambers, and changes in their tension were measured. Fentanyl (100 ng/ml) had no effect on resting tension of unstimulated rings on a contraction evoked by serotonin 10(-8) to 10(-4) M. In rings with endothelium, the opioid had a minimal depressant effect on the contractile response to phenylephrine. Tension of vessels precontracted with serotonin (3 x 10(-7) M), or phenylephrine (10(-5) M) was unchanged following fentanyl at 10, 30, 70, or 150 ng/ml. Computerized quantitative angiography was used in intact pigs anesthetized with ketamine to determine the effects of fentanyl on coronary artery diameters of vessels with or without endothelium. Intravenous fentanyl 50 and 250 micrograms/kg had no effect on vessel diameters. Isolated perfused rat hearts were used to assess fentanyl effects upon coronary flow and arteriolar tone and upon myocardial energy state. Coronary blood flow was not altered by fentanyl (100 ng/ml) and was unchanged following washout of the drug. The heart maintained a normal energy status prior to and following fentanyl treatment. These data demonstrate that, under the conditions tested, fentanyl is devoid of major effects on the coronary circulation and upon myocardial metabolism. PMID- 2310037 TI - What is the safest foil tape for endotracheal tube protection during Nd-YAG laser surgery? A comparative study. AB - Metallic tapes have been shown to protect combustible endotracheal tubes from the CO2 laser; however, no adequate means of protecting such tubes from the Nd-YAG laser has yet been found. In this investigation, five different metallic tapes were evaluated as protection for red rubber endotracheal tubes from an Nd-YAG laser set to 50 W. Radio Shack no. 44-1155 and 3M no. 1430 were quickly perforated by the laser. Laser contact with the adhesive side of 3M no. 433 resulted in combustion. The nonadhesive side of the Venture copper tape was not affected by the laser; however, when its adhesive side was struck, a fire occurred. 3M no. 425 tape provided the best protection: no effect was seen when the laser was aimed at its nonadhesive side for 1 min, with only smoking of the tape evident when its adhesive side was tested. Finally, 3M no. 425 and Venture copper foil tapes were shown to be resistant to an Nd-YAG laser set to 110 watts in an atmosphere of 98% O2. PMID- 2310038 TI - Methylprednisolone acetate does not cause inflammatory changes in the epidural space. AB - Few studies have examined the possible adverse effects that epidural injection of depot corticosteroid preparations may have on meningeal membranes and nervous tissue. Thirty-six healthy adult white rabbits received 0.3 ml/kg epidural injections of either lactated Ringer's solution (negative control group), 1% lidocaine containing methylprednisolone acetate (study group), or normal saline containing talc (positive control group). Animals were killed either 4 or 10 days after injection and stained sections of the spinal cord and meningeal membranes were examined by light microscopy. In all animals that received either lactated Ringer's solution or lidocaine with methylprednisolone acetate, microscopic examination of specimens taken from the L5-L6 interspace revealed no white cell infiltrates and no fibroblastic activity. All animals that received epidural injections of normal saline containing talc had marked infiltration of tissue macrophages in the epidural space. There was no thickening of the meningeal membranes or nerve roots in any animal. The complete lack of inflammatory changes and meningeal thickening demonstrated in this pilot study helps to confirm the safety of methylprednisolone acetate when injected into the epidural space. PMID- 2310039 TI - Severe dynamic left ventricular outflow tract obstruction following aortic valve replacement diagnosed by intraoperative echocardiography. PMID- 2310040 TI - Caudal anesthesia and intravenous sedation for repair of giant bilateral inguinal hernias in a ventilator-dependent premature infant. PMID- 2310041 TI - A new double-angle blade for direct laryngoscopy. PMID- 2310042 TI - A contingency plan for tracheal intubation. PMID- 2310043 TI - All subjects of a study should provide informed consent. PMID- 2310044 TI - Humidification of inspired gas. PMID- 2310045 TI - Preoperative fasting of children. PMID- 2310046 TI - Suprascapular nerve block: a safer technique. PMID- 2310047 TI - Skin perfusion pressure assessed by measuring the external pressure required to stop blood cell flux. AB - Laser Doppler flowmetry (LDF) was used to determine the point at which blood flow cessation is achieved under circumferentially applied external counter pressure at the ankle level. In 13 individuals with a normal ankle index, the flow of cessation external pressure (FCEP) was, on average, 28 mmHg lower than the systolic ankle pressure (range: 7-62). In 19 patients with an ankle index below 1.0, FCEP correlated with the ankle pressure (rs = 0.76) and even more closely with the ankle index (rs = 0.82). In patients with a more pronounced degree of arterial occlusive disease, FCEP can be equal to or even higher than the ankle pressure. This may be due to a release of sympathetic vasoconstrictor tone and possibly to the presence of a collateral circulation supplying the skin. Individual LDF values from the skin at rest do not reflect the degree of peripheral circulatory insufficiency. PMID- 2310048 TI - An angiographic study of intracardiac coronary arteries from human autopsy hearts: their clinicopathologic significance and characterization during transmural myocardial infarction. AB - In this study of human autopsy hearts, coronary arteries were divided by morphologic criteria into classes A (branching-type) and B (straight-type) arteries. Infarcted hearts and normal hearts were investigated mainly by means of coronary angiography, as well as by gross and histologic examinations. Transmural myocardial infarction originated in the inner half of the myocardial layer, which was predominantly supplied by class A arteries, followed by gradual extension to the outer layer. The early infarcted focus revealed an angiographically avascular state. This may have been the result of shrinkage of the peripheral branches of class A arteries due to increased extravascular resistance rather than to arteriolar obstruction by small thrombi and/or leukocyte plugs. By contrast, class B arteries remained patent and were almost entirely free from such phenomena. They usually penetrated the infarcted focus to drain into the papillary muscles and trabeculae carnae. As the process of myocardial infarction progressed, various patterns of vascular reactions corresponding to the healing phase were demonstrated by these branches within the infarcted foci. The passive response of class A arteries during acute ischemia characterized the early myocardial lesion. Subsequently, neovascularization from the surviving class B arteries in the infarcted focus occurred as a part of the formation of granulation tissue. Newly formed small arteries from class A arteries also participated in this reaction at the marginal area of the lesion. These well coordinated vascular reactions revealed in greater detail the initiation and progression of the healing process and were reflective of the clinical prognosis. PMID- 2310049 TI - The ST segment axis as a differential diagnostic feature between acute pericarditis and acute inferior myocardial infarction. AB - The ST segment electrical axis in the frontal plane was calculated in 20 patients with an acute inferior myocardial infarction (AIMI) and another 20 patients with the acute phase of pericarditis (AP). The ST segment axis of patients with AIMI ranged from 100 degrees-120 degrees (mean 114 degrees). The ST segment axis of patients with AP ranged from 30 degrees-60 degrees (mean 45 degrees). Thus, the ST segment axis can be used for the differential diagnosis in the early acute phase, especially when there are no other important distinguishing factors between these two conditions. PMID- 2310050 TI - Do vasospasms provoke ocular diseases? AB - Vasospasms in the eye are often combined with digital vasospasms, as can be diagnosed with a nailfold capillaroscopic local cooling test. In 16 patients with a history of cold hands and feet the presence of peripheral vasospasms without any underlying disease was demonstrated by means of nailfold video capillaroscopy. These patients showed the phenomenologic diagnosis of low-tension glaucoma with visual field defects characteristic of glaucoma even though intraocular pressure above 21 mmHg was excluded. The visual field defects were not homonymous, indicating a prechiasmal location of the vascular disturbance. Ocular vasospasms cause visual field damage that can be aggravated or provoked by cooling one hand in cold water and that often improves after treatment with the calcium channel blocker nifedipine. The results suggest that vasospasms not only are present in Raynaud's disease, migraine, and Prinzmetal's variant angina but also may be an important factor in the genesis of low-tension glaucoma. This is a new finding and may be related to a general vasospastic syndrome. PMID- 2310051 TI - Lower extremity amputation: open versus closed. AB - Wound breakdown was assessed in 117 amputations for nonhealing lesions and peripheral vascular closure (chi 2 10.34). Nonhealing occurred in 10/63 amputations with primary skin closure when compared with those not closed (p less than .01). All 54 amputation sites treated by the open technique healed without revision. Of 22 toe amputations, the open technique performed in 14 patients required a mean of nine postoperative days; the closed-toe amputation technique performed in 8 patients needed a mean of 5.8 days; the closed-toe amputation requiring revision needed a mean of 36.3 days. Healing rates were significantly different when the wound was left open versus primarily closed (chi 2 8.56 p less than .01). Nineteen transmetatarsal amputations (TMA) were completed; 10 open TMAs required a mean of twenty-four days; 9 closed TMAs required a mean of fifteen days; and revision a mean of eighteen days. Of 51 below-the-knee amputations (BKA), 20 open BKAs required a mean of thirteen days; 3 closed BKAs required a mean of 18.5 days; and 1 revision required two hundred fifty-eight days postoperatively. Twenty-five above-the-knee amputations (AKA) were performed; the 10 open AKAs required a mean of sixteen days; the 15 closed AKAs required a mean of eleven days. There was no significant difference in healing rates of TMA, BKA, or AKA. Healing rates of toe amputations and amputation overall are, however, significantly different. Closed lower extremity amputation wounds require fewer hospital days than open, except if problems in wound healing require revision. PMID- 2310052 TI - Prevalence and risk factors of varicose veins in Japanese women. AB - The prevalence and risk factors of varicose veins in Japan were investigated in 541 Japanese women. Varicose veins were defined as any dilated, tortuous, and elongated veins of the lower extremity and classified into four types. The total prevalence rate was 45%. Saphenous type was observed in 22%, segment type in 35%, reticular type in 28%, and web type in 16%. Varicose veins in Japan seem to be less common than in the United States and Europe but more prevalent than in Africa. Concerning risk factors for varices, age, sex, heredity, and childbirth were related to the incidence of varicosities, as reported by others. However, these risk factors were shown to differ according to type of varicose veins. PMID- 2310053 TI - Permeability of intracranial blood vessels to endogenous serum albumin. AB - The blood-brain barrier to endogenous serum albumin labeled with Evans blue was studied by standard fluorescence microscopic techniques in cats. Systematic studies confirm that, except in certain well-known loci (hypothalamic median eminence, subfornical organ, area postrema, etc.), blood vessels within brain tissue are impermeable to endogenous albumin. But studies also demonstrate that in virtually all arteries at the base and over the surface of the brain and brain stem, labeled albumin passes readily through endothelium and the vascular wall to the adventitia. These observations are discussed in the context of current concepts of intracranial vascular permeability and, in terms of general biology, the possible consequences of the permeability to serum albumin of intracranial, extraparenchymal blood vessels on the composition and physiology of cerebrospinal fluid and in the pharmacokinetics of antibiotics, anticonvulsants, and antineoplastic and vasoactive agents. PMID- 2310054 TI - Pulsed and color Doppler analysis of normal carotid bifurcation flow dynamics using an in-vitro model. AB - An anatomically accurate model of the human carotid bifurcation was studied by using color Doppler flow mapping and pulsed Doppler signal analysis. In concordance with dye injection studies, a zone of flow separation was clearly demonstrated at the origin of the internal carotid artery opposite the flow divider. This zone of flow reversal was detected when the ratio of external to common carotid flow rates was greater than 0.27 and became progressively larger as the ratio increased, finally evolving into a zone of heterogenous flow at a ratio greater than 0.5. The authors conclude that the zone of flow reversal seen in the human carotid artery is a geometric property of the bifurcation and that its size depends on the relative flow between both branches. Doppler color imaging can be used to noninvasively map out its extent. PMID- 2310055 TI - Management of multiple cholesterol embolization syndrome--a case report. AB - A sixty-two-year-old man who underwent coronary angiography and received acute thrombolytic and anticoagulant therapy for acute myocardial infarction developed multisystemic injury, including renal insufficiency and cutaneous manifestations. Fundoscopic examination and skin biopsy specimen led to the diagnosis of multiple cholesterol embolization syndrome (MCES). Discontinuation of anticoagulants and administration of hemostatic (carbazochrome, tranexamic acid, reptilase, and vitamin K) and antihyperlipidemic (cholestyramine and probucol) drugs resulted in temporary improvement of cutaneous and renal disorders and extended survival for about one year. Besides severe aortic atherosclerosis, postmortem examination revealed numerous cholesterol emboli to multiple organs. MCES is a rare but serious complication of left heart catheterization and anticoagulant therapy, and the optimal treatment remains to be established. The authors suggest here that the above-mentioned therapy might be effective for management of MCES. PMID- 2310056 TI - Drug dependence in the differential diagnosis of allergic respiratory disease. PMID- 2310057 TI - IgE antibodies to hydrolysates of cow milk proteins in children with cow milk allergy. AB - Milk substitutes such as protein hydrolysates are largely used in children with cow milk allergy. The clinical benefit of these preparations is still a matter of debate. In the present study, IgE directed against protein hydrolysates was detected in 6/13 in children with cow milk allergy. PMID- 2310059 TI - Parietaria: an unrecognized cause of respiratory allergy in the United States. AB - Parietaria is considered the ragweed of the Old World. There are no prior reports of respiratory allergy due to Parietaria (P.) in North America. Following the identification of a lead case, 100 grass-sensitive patients who suffered from seasonal respiratory allergy were skin tested to P. judaica (P.j.) and P. officinalis (P.o.). Eight percent reacted. Five of 42 females (12%) and three of 58 males (5%) demonstrated skin test reactivity to extracts of P.j. and P.o. All reacted to P.j. There was a greater incidence (P less than .05) and reaction size (P less than .05) in females. PMID- 2310058 TI - Predictive value of monitoring expiratory peak flow rates in hospitalized adult asthma patients. AB - This prospective single-blind study monitored the progress and outcome of 18 hospitalized asthmatic patients on intravenous corticosteroids by daily peak expiratory flow rate (PEFR) measurements to determine whether daily flow monitoring was useful as a guide for predicting response to therapy over the short- and long-term course posthospitalization. Daily monitoring of PEFR was helpful in demonstrating the response to therapy during hospitalization and at follow-up visit (1 to 2 weeks) posthospitalization. This change in PEFR during acute hospitalization and at initial follow-up visit did not correlate well with relapse or repeat hospitalization during the 5- to 17-month follow-up period. PMID- 2310060 TI - Evaluation of partially purified salivary gland allergens from the Australian paralysis tick Ixodes holocyclus in diagnosis of allergy by RIA and skin prick test. AB - Two diagnostic assays that detect IgE specific to I. holocyclus were developed using purified sources of allergens. Salivary gland extract was superior to whole body extract in both the radioimmunoassay and the skin prick test. Of the partially purified salivary gland allergens, the 28-KD protein fraction gave the most promising results. PMID- 2310061 TI - Lack of preventive measures given to patients with stinging insect anaphylaxis in hospital emergency rooms. AB - A survey of patients receiving venom immunotherapy revealed that at the time of emergency treatment of their anaphylactic reaction, a significant percentage had not received appropriate avoidance instruction, a prescription for epinephrine, or referral to an allergist. Emergency room personnel must be instructed in giving appropriate advice after insect sting anaphylaxis. PMID- 2310062 TI - Epidemiology of immunoglobulin E levels in a defined population. AB - Age-adjusted geometric mean IgE levels in 621 older subjects were higher in men (26.3 kU/L) than in women (19.1 kU/L), and decreased with age. The higher levels in men were largely a result of a strong positive association with cigarette smoking. Among allergic conditions, a personal history of asthma was associated with the highest IgE levels. In multiple linear regression models in men, cigarette smoking was the single strongest correlate of IgE levels, while a personal history of allergy was the strongest correlate in women. Our results suggest important nonallergic as well as allergic determinants of IgE levels in populations. PMID- 2310063 TI - Caveat emptor: allergic rhinitis. AB - This case report illustrates that the typical symptoms of allergic rhinitis- rhinorrhea, itchy eyes, nose and throat--should not be taken as a routine phenomenon without consideration of other differential diagnoses. Caveat Emptor: "allergic rhinitis." PMID- 2310064 TI - Effects of epinephrine and norepinephrine on cerebral oxygen delivery and consumption during open-chest CPR. AB - The effect of epinephrine and norepinephrine on cerebral oxygen delivery and consumption after five minutes of cardiopulmonary arrest and three minutes of open-chest cardiac massage was studied in 21 pigs. Norepinephrine, like epinephrine, has a marked alpha- and beta 1-sympathomimetic activity, but compared with epinephrine, the degree of beta 2-stimulation is weak. Epinephrine probably stimulates cerebral oxygen and glucose consumption by its beta 2 adrenergic effect. After three minutes of CPR, three groups of seven animals each blindly received either placebo (control group), 45 micrograms/kg epinephrine, or 45 micrograms/kg norepinephrine. During CPR but before drug administration, cerebral blood flow was 23 +/- 14 mL/min/100 g in the control group, 30 +/- 7 mL/min/100 g in the epinephrine group, and 30 +/- 11 mL/min/100 g in the norepinephrine group. At 90 seconds after epinephrine, cerebral blood flow increased to 54 +/- 14 mL/min/100 g and after norepinephrine, to 58 +/- 22 mL/min/100 g (P less than .05). Cerebral perfusion pressure for both drugs was significantly higher than the control group. Compared with mechanical measures alone, cerebral oxygen delivery rose from 4.3 +/- 1.2 to 7.4 +/- 1.7 mL/min/100 g after epinephrine and from 3.7 +/- 1.4 to 7.3 +/- 2.7 mL/min/100 g after norepinephrine (P less than .05). There was no increase in cerebral oxygen consumption after both catecholamines, and cerebral oxygen extraction ratio decreased. Cerebral glucose delivery increased in relation to glucose consumption, and extraction ratio did not change significantly after both catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310065 TI - Refusing care to patients who present to an emergency department. AB - In July 1988, our emergency department adopted a policy of refusing to treat patients in the ED if they failed to have what was considered an emergency condition. Screening examinations were performed by triage nurses to determine whether patients were eligible to be seen in the ED. Patients whose vital signs fell within specific categories and who had one of 50 minor chief complaints were refused care in the ED and referred to off-site clinics. The referral of these patients out of the ED after a screening examination falls within the scope of legislation governing ED care and transfer (federal COBRA, Cal SB-12, and Title 22) as determined by the University of California legal counsel. In the first six months of this new triage system, 4,186 patients were referred from the ED; this represented 19% of total ambulatory patients who presented to the triage area. Of the 4,186 patients refused care, 84% were referred to off-site nonuniversity clinics, and 15% were referred to a university-affiliated faculty-staffed clinic. Follow-up letters and telephone calls to their clinics identified no patients who needed retriage to an ED, and only 54 patients (1.3%) complained about their referral out of the ED. Only 42 patients returned to the ED within 48 hours of initial triage, and none had a deterioration of their condition. In conclusion, a selective triage system may be used to effectively decompress an ED, although further study is needed to identify potential rare adverse outcomes. PMID- 2310066 TI - Relative bradycardia in patients with isolated penetrating abdominal trauma and isolated extremity trauma. AB - A relative bradycardia is sometimes seen in patients with hemorrhagic shock. The phenomenon of relative bradycardia in civilian patients with isolated penetrating abdominal trauma and isolated severe extremity trauma who presented to an urban trauma center was studied retrospectively. Relative bradycardia was defined as a pulse rate of less than 100 with a concomitant systolic blood pressure of less than 100 mm Hg. There were 256 patients with isolated penetrating abdominal trauma and 938 patients with isolated severe extremity trauma. The incidence of relative bradycardia was 3.1% (eight of 256) in the group with abdominal trauma and 1.8% (17 of 938) in the group with extremity trauma. A pulse rate less than 100 was documented in 35.2% of all patients presenting with a systolic blood pressure less than 100 mm Hg (25 of 71). A pulse rate of less than 100 was documented in 45.8% of all patients presenting with a systolic blood pressure less than 90 mm Hg (11 of 24). No increased mortality was seen in the patients who evidenced relative bradycardia. The effect of intraperitoneal bleeding on the normal tachycardic response to hemorrhage also was studied. After controlling for volume status using various operational definitions of shock, no statistically significant (P less than .01) difference in pulse rates was noted between patients with isolated penetrating abdominal trauma and isolated extremity trauma. This result suggests that the previously theorized vagal-mediated bradycardia unique to intraperitoneal bleeding may not exist. PMID- 2310067 TI - Prehospital cricothyrotomy: an investigation of indications, technique, complications, and patient outcome. AB - The records of all patients who presented to a Level 1 trauma center during a two year period for whom a prehospital cricothyrotomy was attempted or ordered were reviewed. Twenty patients met the study criteria. The average age was 37 years (range, 11 to 65 years). Indications for prehospital cricothyrotomy were massive facial trauma (eight), failed oral intubation (seven), and suspected cervical spine injury (one). Cricothyrotomy was attempted in 16 patients (80%), with the remaining four having the procedure ordered but not attempted. A successful airway was achieved in 14 patients (88%). Horizontal incisions were used in all cases and were anatomically correct in 15 of 16 attempts (94%). The overall immediate complication rate was 31%. Two patients (12%) sustained major complications (failure to obtain an airway). No hemorrhagic complications occurred, but 16 of the 20 were in cardiac arrest in the field. Long-term complications were not evaluated. All patients sustained major injuries (mean Injury Severity Score, 53.7), except one patient who suffered airway obstruction from food. Three patients (15%) survived; two of the three suffered permanent, severe brain dysfunction. These preliminary findings demonstrate that prehospital cricothyrotomy is being used chiefly in massively injured patients who are already beyond recovery. It is thus difficult to assess whether the procedure is either safe or effective. There is a need for further investigation to determine whether prehospital cricothyrotomy has any beneficial effect on outcome and, if so, in what setting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310068 TI - A computer-assisted quality assurance audit in a multiprovider EMS system. AB - Prehospital care delivered by multiple agencies and their paramedics in a suburban emergency medical services (EMS) system was compared to assess the impact of a receiving hospital quality assurance audit on paramedic and agency performance. A committee of physicians, nurses, and paramedics developed performance criteria based on a county EMS protocol. Run tapes were reviewed to assess accuracy of runsheets. Deviations were categorized and tabulated with Lotus 1-2-3 software. A profile was developed for each agency and paramedic. Results were returned to supervisors of each agency on an intermittent basis with subsequent feedback to paramedics. Four agencies and 100 paramedics were audited during the 18-month study period, with a total of 2,406 runsheets reviewed. Average deficiencies per run per quarter for all paramedics decreased from 0.47 to 0.34 (P less than .006). For one agency, deficiencies per run declined from 1.98 to 1.06, although this was not statistically significant (P = .068). During the second nine-month segment of the study, the records of 62 paramedics were reviewed. A mean deficiency per run of 0.39 +/- 0.55 was found, with four paramedics performing more than two standard deviations from the mean. This receiving hospital EMS quality assurance audit has helped document problems in agency procedure performance and individual paramedic performance. It also has improved compliance with county protocol on patients delivered to our institution. PMID- 2310069 TI - Intravenous verapamil in the prehospital treatment of paroxysmal supraventricular tachycardia. AB - The prehospital treatment of paroxysmal supraventricular tachycardia (PSVT) with verapamil alone or in comparison with other interventions has not been studied. A sequential protocol consisting of Valsalva maneuver, ice packs, pneumatic antishock garment inflation, and verapamil 0.5 mg IV was implemented in an urban emergency medical services system after appropriate paramedic education. On-line physician discretion could alter the protocol in specific clinical situations. Inclusion criteria required a narrow-complex regular tachycardia at a rate of between 150 and 250. Of 43 patients identified, the protocol was applied sequentially in 26 (60%) and with valid physician discretion in 15 patients (35%) (due to hypotension, chest pain, or dyspnea). Conversion to a more stable rhythm occurred in 25 patients (59%). Of these, all but one achieved a sinus mechanism. The Valsalva maneuver and ice pack application were ineffective in achieving rhythm conversion, being successful in only two of 33 (6%), one of 31 (3%), and four of 24 (17%) attempts, respectively (P greater than .05). Verapamil, however, was significantly more effective (18 of 24 attempts, 75%) than any of the other interventions either singly (P less than .01) or in combination (P less than .0001). No clinically important adverse effects occurred with any intervention, but application of the protocol increased mean on-scene time to 30.6 minutes. We conclude that verapamil is an effective agent for the prehospital termination of PSVT but that careful on-line physician supervision and a system for confirming rhythm identification are both essential. PMID- 2310070 TI - Introduction to biostatistics: Part 2, Descriptive statistics. AB - Descriptive statistics include measures of central tendency and variability. Measures of central tendency include mean, median, and mode. The mean is the arithmetic average of data from interval or ratio scales. The median reflects the 50th percentile score. The mode is the most frequently occurring value of a data distribution. Measures of variability include range, interquartile range, standard deviation, and standard error of the mean. The range describes the spread between the extreme values of data. Interquartile range is data included between the 25th and 75th percentile of a distribution. Standard deviation describes variability of data about the sample mean, while standard error of the mean helps describe the distribution of several sample means about a true population mean. Finally, confidence intervals, which are derived from the standard error of the mean, define an interval likely to include a true population value, based on sample statistical values and probability charceristics of data distributions. PMID- 2310071 TI - Dissecting thoracic aortic aneurysm in a 22-year-old man. AB - A 22-year-old man presented with a 12-hour history of acute epigastric pain associated with hematochezia. Emergency echocardiography and aortography were diagnostic of a bicuspid aortic valve and dissection of the thoracic aortic aneurysm. Surgical intervention included repair of the aneurysm, partial small bowel resection, and revascularizations of the superior mesenteric artery. An eventful hospital course ended in the patient's death on the eighth postoperative day. Dissecting aortic aneurysm is a rare condition in young adults. Prompt diagnosis with aggressive medical management and urgent surgical consultation affords the best outcome. PMID- 2310072 TI - Four case studies: high-dose epinephrine in cardiac arrest. AB - Animal and human studies have suggested that higher doses of epinephrine than currently recommended may improve resuscitation rates after prolonged cardiac arrest. Because of our failure to resuscitate four patients with the standard American Heart Association protocol for cardiac arrest, we used a larger dose of epinephrine in an attempt to enhance resuscitative efforts. All patients required CPR and had nonperfusing rhythms for at least 20 minutes. The four patients received from 0.12 to 0.22 mg/kg epinephrine. Within five minutes of high-dose epinephrine, all four patients developed perfusing rhythms with maximum systolic blood pressures ranging from 134 to 220 mm Hg. Cardiac dysrhythmias did not occur after these doses of epinephrine. Only one of four patients had ECG evidence of an acute myocardial infarction. In this patient, the history suggested that the myocardial infarction was a primary event, not the consequence of epinephrine. All four patients sustained severe brain injury leading to their demise. This injury was probably due to prolonged cardiopulmonary arrest and global brain ischemia. Pharmacologic and potential pathophysiologic mechanisms of high-dose epinephrine are reviewed. PMID- 2310073 TI - Pathological laughter. AB - A man experienced one hour and 40 minutes of continual, inappropriate, uncontrollable laughter. The onset was preceded by a single-inhalation exposure to an insecticide of very low toxicity. The episode was terminated by a single dose of IV diazepam. A discussion of pathological laughter, including its proposed pathophysiology, differential diagnosis, clinical relevance, and management, is presented. PMID- 2310074 TI - Models for teaching emergency medicine skills. AB - Teaching and retaining psychomotor skills presents problems in emergency medicine. A variety of models, including animals, plastic models, paid or unpaid volunteers, patients recently pronounced dead, and cadavers (the bodies of people who donate their bodies to science), have been developed to alleviate this problem. Practical and ethical concerns in using these models are discussed, with an emphasis on the cadaver model and on those procedures that are best taught on cadavers. PMID- 2310075 TI - Hospital and emergency department overcrowding. PMID- 2310076 TI - Principles of appropriate patient transfer. PMID- 2310077 TI - Analysis of return visits. PMID- 2310078 TI - Prehospital cardiac arrest therapy. PMID- 2310079 TI - Studies on prehospital pharmacologic therapy. PMID- 2310080 TI - Tympanic membrane thermometers. PMID- 2310081 TI - Saliva teststrips for alcohol testing. PMID- 2310082 TI - Mediationism and the obfuscation of memory. AB - Memory theorizing is going nowhere. The reason is that it is rooted in mediationism, the doctrine that memory is mediated by some sort of memory trace. Mediationism is the basic tenet of those who seek the substrate of memory; for students of memory per se it is merely a metaphor, and moreover an unfruitful one, for it cannot be penetrated by the methods of psychology. The rejection of mediationism would serve both to replace mechanistic theories with laws or other modes of explanation and to focus research on the actual experience of memory and on the context in which it occurs. The ensuing advantages are discussed and illustrated. PMID- 2310083 TI - Use of inpatient mental health services by members of ethnic minority groups. AB - National data on psychiatric hospitalization point to marked ethnic-related differences. Blacks and Native Americans are considerably more likely than Whites to be hospitalized; Blacks are more likely than Whites to be admitted as schizophrenic and less likely to be diagnosed as having an affective disorder; Asian Americans/Pacific Islanders are less likely than Whites to be admitted, but remain for a lengthier stay, at least in state and county mental hospitals. These differences are clear-cut, but they ignore a major source of care: psychiatric hospitalization in placements other than psychiatric units and hospitals. Explanations for observed minority-White differences in hospitalization can be evaluated only partially or not at all: Such explanations include ethnic-related differences in socioeconomic standing and in the prevalence of major psychopathology; differential stigma, or capacity to tolerate or support a dysfunctional significant other; access and use of alternative services; and bias in the behavior of gatekeepers, especially practitioners assigning diagnostic labels and making involuntary commitment decisions. More research is needed to help explain these striking differences in utilization. PMID- 2310084 TI - Overview: forging research priorities for women's mental health. AB - After a decade of reports underscoring the inadequacy of existing scientific knowledge for understanding gender differences in mental disorder and its treatment, the National Institute of Mental Health has developed a women's mental health research agenda with five priority areas for research: diagnosis and treatment of mental disorder, mental health issues for older women, violence against women, multiple roles, and poverty. This overview highlights some of the major findings in each of these five areas and introduces the more in-depth treatment given in this Psychology in the Public Form section to the areas of violence, poverty, and multiple roles. It also underscores the importance of identifying sources of gender bias in all mental health research. Women's mental health issues have become officially recognized as part of the NIMH research agenda. Only time and continued monitoring will determine how these official policy priorities will become translated into actual funding and research initiatives. PMID- 2310085 TI - The women's mental health research agenda. Violence against women. AB - The focus of this article is violence against women: scope, impact, community response, clinical treatment, and prevention. Conclusions include the following: (a) Nationally representative data on the scope of violence are lacking. (b) The mental health implications of violence are not currently addressed by the practices of mental health professionals. (c) Discontinuity exists between clinical understanding of the impact of violence and empirical treatment research. (d) Victim services are proceeding in program development without direction from empirical data. (e) Prevention efforts have been isolated from the social context in which violence against women occurs. Nine directions for future research are highlighted that intersect with the stated priorities of the National Institute of Mental Health. PMID- 2310086 TI - Understanding AIDS developmentally: a comment on the November 1988 special issue on psychology and AIDS. PMID- 2310087 TI - Corticosteroids--their biologic mechanisms and application to the treatment of asthma. PMID- 2310088 TI - Evidence that neutrophils do not participate in the late-phase airway response provoked by ovalbumin inhalation in conscious, sensitized guinea pigs. AB - Inhalation of ovalbumin by conscious, sensitized guinea pigs induced two phases of airway obstruction measured at 2 h (EAR) and at 17 h (LAR), respectively. In addition to causing airway obstruction, allergen challenge induced an accumulation in the bronchial lumen of eosinophil and neutrophil polymorphonuclear leukocytes at 17 h. Intraperitoneal injection of guinea pigs with a specific rabbit anti-guinea pig neutrophil serum 24 h before challenge reduced the number of circulating neutrophils by 94% and the airway neutrophilia after challenge by 90%, but it had no effect on the magnitude of either the EAR or the LAR. The observation that the LAR was not effected by neutropenia supports previous conclusions derived from experiments using the anti-allergic drugs, cromolyn sodium and nedocromil sodium, and the beta 2-adrenoceptor stimulant, albuterol, that, although there is a temporal relationship between neutrophil accumulation in the airways and the peak of the LAR, this polymorphonuclear leukocyte does not play a central role in the pathophysiologic processes that give rise to the late-phase response to guinea pig airways. PMID- 2310089 TI - The effect of endotoxin inhalation on airway responsiveness and cellular influx in rats. AB - Studies in humans suggests that airway inflammation may modulate nonspecific airway responsiveness. We studied in a rat model the effect of the inhalation of endotoxin on the cellular composition of the bronchoalveolar lavage (BAL) fluid and airway responsiveness. The exposure to an aerosol of endotoxin caused a rapid influx of neutrophils in the airways. The neutrophils persisted up to 24 h after exposure. Elastase activity in lavage fluid became detectable 30 min after the endotoxin exposure and peaked 9 h later. The exposure to the endotoxin aerosol was followed 1 to 2 h later by a significant increase in the airway responsiveness to 5-hydroxytryptamine (5HT). However, the increase in responsiveness disappeared, and 9 to 12 h following the end of the exposure a significant decrease in airway 5HT responsiveness was observed at the moment that more than 80% of the cells contained in the BAL fluid were neutrophils. The effect of endotoxin on airway responsiveness and inflammation was dose dependent. We also compared in three different inbred rat strains the effect of endotoxin inhalation. The aerosol exposure induced in all three strains a comparable neutrophil influx in the airways, but only two of the three strains became hyperresponsive to 5HT. We conclude that the inhalation of endotoxin causes a neutrophilic airway inflammation in rats. The relationship between this airway inflammation and airway responsiveness is dependent on the time following the exposure and the animal strain used. PMID- 2310090 TI - Abnormalities in airway smooth muscle in fatal asthma. AB - The characteristics of asthmatic airway smooth muscle are poorly described. Using standard organ bath techniques, the in vitro isometric contractile and relaxant responses of tracheal strips obtained from seven asthmatics (A) (mean age, 48 +/- 6 SEM yr) dying during severe asthma attacks outside hospital were studied 7.6 +/ 1.3 h after death. Drug therapy had varied, but it had always included inhaled beta 2-agonists. Control data (C) were obtained from 31 subjects (54 +/- 2 yr) studied 9.5 +/- 0.4 h after sudden nonrespiratory death. Cholinergic contractile and nonadrenergic noncholinergic inhibitory (NANCI) neural responses were studied with electrical field stimulation (EFS); histamine, isoproterenol (ISO), and theophylline (THEO) responses were studied using cumulative techniques. The maximal response (Tmax, g/g tissue) to histamine, cholinergic EFS (A = 61.3 +/- 13.2, C = 33.6 +/- 3.6, p less than 0.0001), (A = 70.3 +/- 11.8, C = 47.3 +/- 4.5, p = 0.041), and acetylcholine (ACh) (A = 101.9 +/- 17.4, C = 62.7 +/- 7.5, p = 0.012) was greater in the asthmatics but NANCI responses were similar. Cholinergic Tmax (EFS) as a percentage of Tmax (ACh), EC50 (histamine), and EF50 (EFS) were similar in the two groups. With tissues contracted to 60% of maximum with histamine, the concentrations of ISO (A = 60.3 nM, C = 12.7, p = 0.01) and THEO (A = 31.9 microM, C = 5.7, p = 0.041) to reduce tension by 50% (IC50) were greater in asthmatics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310091 TI - Pulmonary gas exchange in severe chronic asthma. Response to 100% oxygen and salbutamol. AB - Ventilation-perfusion (VA/Q) inequality has been evaluated using the multiple inert gas technique in nine nonsmoking patients (mean +/- SD, age 56 +/- 10 yr) with stable, severe, chronic asthma (partially reversible airway obstruction; baseline FEV1, 39 +/- 10% predicted) before and during 100% O2 breathing and then 15 min after three puffs (300 micrograms) of inhaled salbutamol. The aim of this study was to investigate whether this type of asthma was associated with a different pattern of VA/Q inequality from that observed in acute episodes and in particular to determine whether the VA/Q pattern was fixed or could be altered by bronchodilator agents or O2 breathing. The predominant pattern of VA/Q distribution was broad and unimodal but without shunt (VA/Q = 0) or low VA/Q areas (VA/Q less than 0.1 to greater than 0.005). The amount of VA/Q inequality as assessed by the dispersion of the distribution of pulmonary bloodflow (log SDQ) was not great (log SDQ, 0.77 +/- 0.09), and no correlation was found with the degree of airway obstruction, PaO2 or AaPO2. During 100% O2 breathing, VA/Q inequality worsened (from log SDQ of 0.77 +/- 0.09 to 1.11 +/- 0.21, p = 0.01) with an increase in the perfusion of low VA/Q units (from 0.43 +/- 0.66% to 6.3 +/- 6.5%, p = 0.02) but still no development of shunt. This suggests the presence of hypoxic pulmonary vasoconstriction breathing air, possibly contributing to the preservation of VA/Q relationships.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310092 TI - Pulmonary rehabilitation in lung disease other than chronic obstructive pulmonary disease. AB - The benefit of pulmonary rehabilitation is well documented for patients with chronic obstructive pulmonary disease (COPD). However, such benefit has not been demonstrated for severely impaired patients with other chronic pulmonary diseases. Occasional non-COPD patients have been admitted to our 4-wk inpatient program. We compared the improvement of these non-COPD patients with that of COPD patients in the same program. Improvement is assessed by a 6-min walk test done at admission and discharge. On the admission 6-min walk test, 32 non-COPD patients had an ambulation distance of 276 +/- 219 ft (SD). At completion of the program, their ambulation distance increased to 574 +/- 367 ft (increase in ambulation 298 +/- 290 ft, P less than 0.0001). Diagnostic subgroups improved to essentially the same extent. The increase in ambulation was not statistically different between non-COPD patients and a series of 317 patients with COPD. Patients severely impaired with chronic pulmonary disease other than COPD benefit from intensive pulmonary rehabilitation, and the degree of improvement is similar to that of COPD patients. PMID- 2310093 TI - Acute and long-term amiloride inhalation in cystic fibrosis lung disease. A rational approach to cystic fibrosis therapy. AB - Cystic fibrosis (CF) is the most common inherited fatal disorder among Caucasians. Bronchial mucus in CF contains more potassium and less sodium, which may be due to increased sodium absorption, resulting in a reduced airway water content. We studied 23 patients with CF after inhalation of normal saline or amiloride (10(-3) M), a sodium transport blocker. Mucociliary clearance (MC) and cough clearance (CC) were determined with a gamma camera that traced the movement of 99mTc-labeled, hardened erythrocytes over a 1-h period after the patients inhaled these particles as an aerosol. Before and after each investigation pulmonary function tests (PFT) and blood pressure (BP) were measured. Sputum thread formation was measured by means of a filancemeter. Six of the patients also completed a 3-wk trial of amiloride inhalation therapy. MC increased significantly (p less than 0.001) after acute amiloride inhalation (bronchial deposition, 0.07 mg amiloride) compared with that in the saline control. CC also increased, but not as much as MC. After 3 wk of amiloride inhalation (2 times a day) clearance values (both MC and CC) were markedly enhanced (p less than 0.01); after a similar period of saline inhalation, clearance values were not different from baseline. Sputum filance values also decreased significantly after amiloride inhalation. There were no adverse effects of the amiloride inhalation compared with saline. We conclude that amiloride inhalation administered as a single dose or as long-term therapy is able to increase MC and CC in CF airways and that the effect of 10(-3) M amiloride inhalation on MC lasts at least 40 min. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310094 TI - Ventilatory function and chronic mucus hypersecretion as predictors of death from lung cancer. AB - The relation of ventilatory function and chronic mucus hypersecretion to death from lung cancer has been studied in 13,946 subjects randomly selected from the general population of the city of Copenhagen, Denmark. During the 10-yr follow up, 225 subjects died from lung cancer. Percent predicted FEV1 (%FEV1) and presence of chronic phlegm were used to characterize ventilatory function and chronic mucus hypersecretion, respectively. Mortality analysis employed the multiple regression model of Cox and included age, sex, pack-years of smoking, and inhalation as confounding factors. %FEV1 and chronic phlegm were found to be significant predictors of death from lung cancer. In both men and women with chronic phlegm, the risk of dying from lung cancer was 1.5 greater than in those without phlegm. Compared with subjects with %FEV1 greater than or equal to 80, the subjects with %FEV1 less than 40 and those with %FEV1 between 40 and 79 had a 3.9 and 2.1 higher risk of lung cancer death, respectively. A similar regression model in which %FEV1 was replaced with the ratio of FEV1 to FVC (FEV1/FVC) showed that lowered FEV1/FVC was also a significant predictor of lung cancer death, the subjects with FEV1/FVC less than 0.6 (0.6 to 0.7) having a 2.6 (1.5) higher risk for lung cancer death than those with FEV1/FVC greater than or equal to 0.7. It is concluded that lowered ventilatory function and chronic mucus hypersecretion are both significant predictors of death from lung cancer, even after standardization for smoking. PMID- 2310095 TI - Exercise dysfunction in patients seropositive for the human immunodeficiency virus. AB - To confirm the presence of exercise dysfunction in patients seropositive for the human immunodeficiency virus (HIV), 32 such patients without AIDS were evaluated with cardiopulmonary exercise testing, pulmonary function testing, bronchoalveolar lavage, chest roentgenography, and gallium scanning. No evidence of pulmonary opportunistic infection was found. When compared to an otherwise similar group of HIV-seronegative controls, the patients exercised to a significantly lower workload (195 +/- 30 versus 227 +/- 31 W, p less than 0.001). The ventilatory anaerobic threshold (VAT) values were also significantly lower for the patients (49.2 +/- 13.0 versus 61.9 +/- 9.1% of maximum predicted VO2, p less than 0.001). Nine of the patients had VAT values less than the 95% confidence interval for the controls. This subgroup exercised to a significantly lower maximum VO2 (69.9 +/- 11.2 versus 95.9 +/- 17.5% of maximum predicted VO2, p less than 0.001) and workload (165 +/- 21 versus 227 +/- 31 W) when compared to the control group. These patients demonstrated a mild tachypnea throughout exercise relative to the controls and had a significant increase in the slope of the heart rate to VO2 relationship. These findings are most consistent with a limitation of oxygen delivery to exercising muscles, which may represent occult cardiac disease in this group. PMID- 2310096 TI - Oxygen delivery and consumption and ventricular preload are greater in survivors than in nonsurvivors of the adult respiratory distress syndrome. AB - In patients with adult respiratory distress syndrome (ARDS), oxygen consumption (VO2) is pathologically dependent on oxygen delivery (DO2). Because of alterations in ventricular function, DO2 may be inadequate to satisfy oxygen demand and may contribute to multiple-system organ failure (MSOF). To determine whether there are differences in DO2, VO2, ventricular function, and MSOF, between survivors and nonsurvivors of ARDS, we studied 29 patients without cardiac disease early in the course of ARDS (hypoxemia, diffuse bilateral pulmonary infiltrates, and pulmonary artery occlusion pressure less than 18 mm Hg). Simultaneous hemodynamic, radionuclide cineangiographic, and oxygen transport measurements were made within 24 h of onset of ARDS. Thirteen survivors had greater DO2 and VO2 than did 16 nonsurvivors (p = 0.004 and 0.001, respectively). MSOF developed in no survivors and in 63% of nonsurvivors. In four survivors and in six nonsurvivors in whom DO2 was changed acutely, VO2 was dependent on DO2 (p = 0.014). Survivors had greater stroke volume index and right and left ventricular end-diastolic volume indices than did nonsurvivors despite similar right atrial and pulmonary artery occlusion pressures. There were no differences between survivors and nonsurvivors in biventricular ejection fractions. We conclude that survivors of ARDS have greater DO2 and VO2 than do nonsurvivors. Survival may be explained by the strong inverse relation between DO2 and development of MSOF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310097 TI - A comparison of alpha 1-proteinase inhibitor methoxysuccinyl-Ala-Ala-Pro-Val chloromethylketone and specific beta-lactam inhibitors in an acute model of human polymorphonuclear leukocyte elastase-induced lung hemorrhage in the hamster. AB - A pharmacokinetic model is described for testing of polymorphonuclear leukocyte (PMN) elastase inhibitors administered by intratracheal or aerosol dosing of hamsters. Acute lung injury, measured as hemorrhage occurring within hours after intratracheal instillation of human PMN elastase, correlated directly with the amount of active enzyme instilled. Hemorrhage began within minutes of elastase instillation, was maximal within 1 h, and remained constant for up to 5 h subsequently. Therefore, inhibition of hemorrhage was used as an assay of the effectiveness of various PMN elastase inhibitors given by the intratracheal route. Lung hemorrhage could also be induced by intratracheal instillation of other elastolytic enzymes, such as thermolysin, and inhibition of hemorrhage was seen only with inhibitors active against the type of elastase used. Methoxysuccinyl-alanyl-alanyl-prolyl-valine-chloromethylketone (MeOSuc-AAPV-CMK), as well as alpha 1-proteinase inhibitor (alpha 1PI) but not tosyl-lysine chloromethylketone (tosyl-lysine-CMK), inhibited the hemorrhage caused by human PMN elastase, but the specific inhibitors of this enzyme had no effect on thermolysin-induced lung hemorrhage. The duration of activity of these compounds as elastase inhibitors in this model correlated directly with the extent of their persistence in lung lavage fluid as determined by HPLC analysis of compound recovered by bronchoalveolar lavage. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310098 TI - Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters. AB - Oxidants from cigarette smoke or those produced by phagocytes are implicated in the pathogenesis of emphysema. We reasoned that augmentation of antioxidant enzymes in cigarette smokers may be important in restricting direct and indirect oxidant damage to alveolar structures. Accordingly, we studied the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx), in alveolar macrophages (AM) from cigarette smokers and from smoke-exposed hamsters. The activities of these antioxidant enzymes were compared with the activities found in AM from nonsmoking control subjects. The activities of SOD and CAT from AM of smokers and smoke-exposed hamsters were twice that found in control subjects (p less than 0.01), but there was no change in the activity of GSHPx. Using the hamster model, we found that filtration of smoke attenuated the increase in antioxidant activities, and that after smoking cessation, the increased activities had returned to those found with control subjects. An adaptive response was further suggested by prolonged survival of smoke-exposed hamsters in normobaric hyperoxia (O2 greater than 95%). Chronic smoke exposure in humans or hamsters causes increased SOD and CAT activities in AM. This augmented activity may serve as a mechanism to limit oxidant-mediated damage to alveolar structures. PMID- 2310099 TI - Identification of cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro. AB - The major inhibitor of the cysteine class of proteinases found in human body fluids, such as spinal fluid, milk, and seminal plasma, is cystatin C. In this study we show that human bronchoalveolar fluid also contains cystatin C and examine cystatin C expression by alveolar macrophages in vitro. Immunoprecipitation of extracts of metabolically labeled cells and immunoblotting of cellular extracts and culture media show that cystatin C is synthesized as a 14 (+/- 0.5) kilodalton (kD) protein and that greater than 90% of the protein is released as the 14 kD product into the culture supernatant (26.5 +/- 6.8 ng per 10(6) cells per 24 h). Cystatin C is not one of the most abundant proteins secreted during the first 24 h in vitro, representing approximately 10 to 12% of the total protein released by normal nonsmoker macrophages. Alveolar macrophages obtained from cigarette smokers or nonsmoker macrophages exposed to zymosan in vitro released 10 to 55% less cystatin C than nonsmoker macrophages. We also assayed culture supernatants from macrophages of smokers and nonsmokers for functional cystatin C. Supernatants of nonsmoker macrophages inhibited cathepsin B-like amidolytic activity in a fluorometric assay at pH 5.5. The inhibition was blocked by adsorption with Sepharose-coupled cystatin C antibodies and the inhibitor subsequently recovered from the Sepharose beads. In contrast, supernatants from smoker macrophages had obvious cathepsin B-like activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310100 TI - Sphincters in pulmonary veins. An anatomic study in rats. AB - To better understand blood flow and edema formation in the lung, anatomic evidence for venous sphincters was sought by a scanning electron microscopic investigation of vascular casts in the rat. In the first study, indentations in the casts of veins and arteries were compared. Casts of the pulmonary veins had narrow (1 to 3 microns) circumferential constrictions about every 30 microns in length (range 20 to 50 microns) and before and after accepting tributaries. Most arteries had no constriction. Infrequently, arterial narrowing occurred over long distances (greater than 30 microns). To determine if these indentations could be altered by a neural stimulus, a second study tried to cast the pulmonary microcirculation after the rats were given a blow to the head, but was unsuccessful. In a third study, the pulmonary vasculature of anesthetized rats was cleared and cast. As the resin began to harden and the animals' circulation ceased, half the animals were given a sharp blow on the head. The casts of the veins in the animals that received the blow had deeper bands than the control animals (p less than 0.001). Pulmonary veins have annular constrictions (sphincters) that are strategically located to influence blood flow. They deepen in response to the neural discharge of a head blow and should be considered in the study of neurogenic pulmonary edema. PMID- 2310101 TI - Interstitial lung disease in polymyositis and dermatomyositis. Clinical features and prognosis as correlated with histologic findings. AB - Open lung biopsies from 14 patients and autopsy tissue from one patient with polymyositis/dermatomyositis were reviewed in an attempt to correlate histologic features with clinical, radiographic, and prognostic variables. Three major groups based on histologic patterns were identified: bronchiolitis obliterans organizing pneumonia (BOOP), usual interstitial pneumonia (UIP), and diffuse alveolar damage (DAD). Patients with BOOP had a more favorable prognosis than did patients with UIP. Patients with DAD had a uniformly poor prognosis. One patient had a cellular interstitial pneumonia and did well. Histologic subclassification of the interstitial lung disease proved to be a better predictor of survival than did the radiographic appearance or the clinical presentation. These findings suggest that there is a broader range of histologic findings in polymyositis dermatomyositis than is suggested in the literature and subclassification may be useful for prognosis. PMID- 2310103 TI - Nerve stimulation releases mucosa-derived inhibitory factors, both prostanoids and nonprostanoids, in isolated ferret trachea. AB - The influence of an intact mucosa layer in isolated ferret trachea on the contractile responses to repeated, short-lasting (20 s, every 2 min) nerve stimulations was studied in a nerve-muscle preparation stimulated to cholinergic evoked contractions by either direct vagal nerve stimulation (DNS) or transmural electrical field stimulation (EFS). The contractile responses were monitored by three strain gauges connected to the proximal, middle, and distal segments of the trachea. The mucosa was either left intact (M+) or removed from the membranous part by dissection (M-). The successive decrease in contractile responses was studied for 60 min using repeated DNS and for a further 60 min using alternating EFS and DNS. During the first period, in which DNS alone was used, there was a significantly more pronounced decrease in the M+ preparation compared with the M . This effect was most prominent in the proximal part of the trachea and was not blocked by indomethacin. During the subsequent stimulation period in which alternating EFS and DNS were used, the rate of decrease was significantly greater in all segments. In this phase, however, the inhibitory mucosa-dependent effect was significantly attenuated by indomethacin treatment. In conclusion, this study demonstrates that the mucosa-dependent inhibition or relaxation in ferret trachea is mediated by both a prostanoid and a nonprostanoid factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310102 TI - Effect of volume and dose on the pulmonary distribution of exogenous surfactant administered to normal rabbits or to rabbits with oleic acid lung injury. AB - Administration of exogenous lung surfactant to infants with or at risk for respiratory distress syndrome has been demonstrated to improve gas exchange and survival; administration of surfactant to patients with the adult respiratory distress syndrome is currently undergoing clinical evaluation. Although it is currently assumed the optimal effect will occur when administered surfactant is distributed homogeneously throughout the lung, little is known of the influence of variables inherent in the administration procedure on subsequent distribution. To address this question, we studied the effect of the volume size in which the surfactant is suspended for instillation, and demonstrated a marked relationship in the normal rabbit lung between this volume and the subsequent homogeneity of surfactant distribution. In the rabbit lung that was acutely injured by oleic acid, this relationship was not evident. Concentration of administered surfactant was not demonstrated to be of major influence on its distribution after administration. Our results focus attention on the importance of parameters of the administration procedure, and also demonstrate the usefulness of the techniques used for determination of surfactant distribution. PMID- 2310104 TI - Exercise tolerance during nasal cannula and transtracheal oxygen delivery. AB - Previous studies have reported that exercise tolerance improves with transtracheal oxygen delivery. However, patients were not blinded to the delivery technique used, introducing a potential source of bias. The purpose of this study was to compare exercise tolerance during nasal cannula and transtracheal delivery using a randomized double-blinded technique. Subjects (n = 11) performed 12-min walks on the same day while receiving nasal cannula and transtracheal delivery. Nine of 11 subjects walked farther with transtracheal delivery, a significant increase (p less than 0.01). Mean increase in walk distance was 95 +/- 86 feet. In addition, a trend was seen toward greater improvement in walk distance with greater flows through the catheter (r = 0.58, p less than 0.06). Time into the walk when desaturation (SaO2 less than 90%) first occurred was not significantly different. We conclude that exercise tolerance improves when oxygen is delivered by transtracheal catheter. This improvement is unrelated to an increase in SaO2. We speculate that the increase in exercise tolerance may be related to other physiologic effects of flow through the catheter. PMID- 2310105 TI - Congenital unilateral absence of a pulmonary artery: a report of two adult cases. AB - Congenital unilateral absence of a pulmonary artery (UAPA) is a rare anomaly that is generally diagnosed in childhood and frequently associated with other cardiovascular abnormalities. Two patients with unilateral absence of a pulmonary artery first diagnosed as adults are reported. Our two cases demonstrate that presentation of UAPA may range from an incidental finding to chronic, life threatening symptoms. Because UAPA may require urgent intervention, physicians should be alerted to the possibility of this entity presenting later in life. PMID- 2310106 TI - Effect of opposite changes in cardiac output and arterial PO2 on the relationship between mixed venous PO2 and oxygen transport. PMID- 2310107 TI - The effects of heat and water exchange in the recovery period after exercise in children with asthma. PMID- 2310108 TI - Aphthous ulceration of the gastrointestinal tract in patients with the acquired immunodeficiency syndrome (AIDS). PMID- 2310109 TI - Hyperkalemia associated with diarrhea. PMID- 2310110 TI - Ulcerative colitis and marijuana. PMID- 2310111 TI - Ethical questions about pay for research. PMID- 2310112 TI - Diclofenac sodium and bruising. PMID- 2310113 TI - Heparin-associated thrombocytopenia and immunoglobulin therapy. PMID- 2310114 TI - Danazol and idiopathic thrombocytopenic purpura. PMID- 2310115 TI - Measles vaccine and travelers. PMID- 2310116 TI - Iritis and papillitis as a primary presentation of Lyme disease. AB - A 9-year-old boy had iridocyclitis and papillitis. Laboratory evaluation revealed a positive Lyme titer. Institution of therapy with intravenous ceftriaxone resulted in regression of the ocular inflammation. Ophthalmologists should consider Lyme disease in the differential diagnosis of iridocyclitis in conjunction with papillitis. PMID- 2310117 TI - Ketamine anesthesia in pediatric ophthalmic office procedures (October 1985 October 1986). AB - We describe a prospective study of 18 pediatric ophthalmic patients given low dose intramuscular ketamine hydrochloride as the sole or adjunct anesthetic agent. Our results indicated that there was a low incidence of side effects with successful operative outcomes. PMID- 2310118 TI - The treatment of foveal central serous choroidopathy by krypton red laser. AB - We present 24 patients with recent foveal central serous choroidopathy. Only those in whom the leakage site was located within a radius of 250 microns from the foveal center were included in this study. All patients were treated with the krypton red laser (647 nm) within a week of the clinical diagnosis. At the end of the follow-up, 70.8% of the patients had a visual acuity of 6/8.5 or better, and an overall visual improvement was found in 83.3%. In 90% of the patients whose vision improved, significant absorption of subretinal fluid was seen within three weeks and in 10% within four weeks. No evidence of any macular pathology complicating the laser treatment was found at the end of the follow-up period of at least 36 months. PMID- 2310119 TI - Isolated unilateral hemichoroidal melanosis. AB - Ocular melanosis is usually diffuse but may be sectoral. An unusual case of isolated unilateral hemispheric choroidal melanosis is presented in a patient with uveitis. Details of the embryologic basis for this condition remain speculative. PMID- 2310120 TI - Retinochoroidal coloboma: varieties of clinical presentations. AB - Several presentation and associated clinical problems can be seen with retinochoroidal colobomas. We review five cases of retinochoroidal coloboma with no specific clinical problems and present five cases with clinical visual impairment. The five symptomatic cases include: one with extensive bilateral involvement; one with associated rhegmatogenous detachment and peripheral tears; one with retinal detachment and apparent holes in the intercalary membrane; one with subretinal neovascularization; and a case with diabetic retinopathy, optic nerve coloboma, and peripheral retinochoroidal coloboma in one eye and a total coloboma in the other eye. PMID- 2310122 TI - [Endoscopy of the eustachian tube. 1st evaluation]. AB - The authors present a novel, original method for exploration of the middle ear cavity using Eustachian tube endoscopy. The diameter of the fibre optic tube was only 0.9 mm, hence the term micro-endoscopy. This endoscopic procedure was used during surgery for chronic otitis, where there was evidence of tubal etiology which required confirmation. The preliminary results are presented. PMID- 2310121 TI - [Value of preserving mandibular continuity in transmandibular bucco pharyngectomy. Apropos of 11 cases]. AB - 84 transmandibular bucco-pharyngectomies were carried out over 6 years between 1983 and 1988. Eleven, i.e. 13%, were performed with preservation of mandibular continuity. Histological examination of resected bone fragments did not demonstrate any bony invasion in 65 cases; in contrast, in 8 cases, extension of the tumour to involve bone was likely due to the topography of the tumour and the results of pre-operative X-ray examination. PMID- 2310123 TI - [A new endonasal therapy: the endoscopic YAG laser]. AB - Therapeutical fiberscopy permits ambulatory treatment of benign lesions of the nose and cavum with the use of a flexible endoscope on a patient in the sitting position. YAG gives access to the nasal fossa and, more particularly, to the cavum conchae where it is of the utmost value, since this area is normally inaccessible under local anesthesia. In the cavum, we have been able to treat primarily inflammatory lesions of the adenoids, bridles, cysts, and cases of epipharyngitis and tubal catarrh. In the nasal fossa, although the YAG method provides a means for resorbing hypertrophic conchae, it is of special values for the management of polyposis. The removal of polyps allows to withhold the utilization of adrenal corticosteroids; to delay surgery; or even to reoperate patients with early recurrences. Two ventilation middle meatotomy operations have also been performed. Results from this destructive but precise method are promising. PMID- 2310124 TI - [Transposition of the temporal muscle and surgery of the middle third of the face. Technic, indications and results]. AB - The authors reemploy the technique using the temporal muscle to fill in large surgical cavities after tumoral surgery of the middle 1/3 of the face. The purpose of this technique is to prevent crust formation after radiotherapy, and to improve esthetic results by preventing further cutaneous retraction. They expose their own technique, the results and the indications from 8 cases. PMID- 2310125 TI - [Spontaneous rhinorrhea of a rare etiology (apropos of empty sella turcica)]. AB - The authors report a case of non traumatic rhinorrhea due to an empty sella turcica. Such an intra sellar arachnoidocele compress the pituitary gland against the posterior wall, erode the floor and lead to CSF rhinorrhea through the sphenoidal sinus. Diagnosis and treatment are best accomplished by a team approach involving otolaryngologist, neurosurgeon and neuroradiologist. CT Scan and IRM explain the diagnosis. Treatment can be accomplished by a transeptal transphenoidal approach with localization and repair of the leak in the absence of increased intracranial pressure. PMID- 2310126 TI - [Transeptal approach to the pituitary fossa. A simplified technic via an exclusively endonasal approach]. AB - An updated Segura operation, this technique combines a pure endonasal septal approach and the insertion of a compact adapted autostatic retractor. It has the benefit of simplicity, has fewer disadvantages and represents an appreciable gain in time. Difficulties have not been encountered provided the usual landmarks associated with transeptal surgery are taken into account. PMID- 2310127 TI - [Use of madreporic material in ear surgery. An initial study]. AB - Numerous surgical techniques now call for biomaterials. Included in this term is material foreign to the receiver, of natural or artificial origin, which is implanted in a living organism in order to repair the impaired function of the organ. By using a recent material, coral, the authors here by relate their experience within the scope of ear surgery. The analysis of the preliminary results encourages the further use of this material, bio-compatible, easily-used and giving excellent functional results. PMID- 2310128 TI - [Isolated ankylosis of the malleus]. AB - Certain cases of apparently isolated conductive deafness, the etiology of which remains uncertain after clinical examination and impedance measurement, can be found in younger patients and adults. Surgical exploration is necessary: this involves, first of all, an inspection of the anatomy of the ossicles and then precise study of their mobility at the level of the tympanic cavity and attic. Various forms of malleus ankylosis, due to blockage or malformation, are presented. Ossiculoplasty gives good auditory results. PMID- 2310129 TI - [Amalgamated and reinforced bone powder graft in the correction of the nasal ridge]. AB - A number of surgical procedures have been described to correct irregularities of the consequences of excessive resection of the nasal ridge. Among these procedures the authors propose a bone powder graft mixed with tissue glue and reinforced with surgicel. The graft is in the form of a sheet of variable thickness which is malleable and can be perfectly shaped to fit the nasal ridge. It is positioned between the osteo-cartilagenous supporting structures and the skin. It smoothes out rough areas and compensates for any underlying loss of substance. It may be combined with a bone or cartilage graft which serves as a support and also acts to smoothe out the irregular form of the latter. PMID- 2310130 TI - Reinnervation of the canine posterior cricoarytenoid muscle with sympathetic preganglionic neurons. AB - This experiment investigated the reinnervation of the canine posterior cricoarytenoid (PCA) muscle with preganglionic neurons of the sympathetic nervous system. Six dogs had their right recurrent laryngeal nerve (RLN) sectioned. Four of these dogs had the sympathetic cervical trunk (SCT) implanted into the right PCA muscle, and the two remaining dogs served as denervated controls. Four months later all dogs underwent videolaryngoscopy, electromyography, and electrical stimulation of the SCT. The PCA muscles were excised, sectioned, and stained for glycogen and ATPase. All four experimental PCA muscles demonstrated electrically evoked abduction and tonic electromyographic activity. In two of the specimens, staining (ATPase and PAS) revealed areas of reinnervation with fiber type grouping and glycogen depletion. These results are consistent with the successful reinnervation of the PCA muscle. Further refinement of this technique could be of benefit to patients with bilateral vocal cord paralysis. PMID- 2310131 TI - Use of nasal valve stent with anterior rhinomanometry to quantitate nasal valve obstruction. AB - Some patients have increased resistance in the nasal valve area that is static and does not collapse. Anterior rhinomanometry is unable to document nasal valve disorders in these instances. A simple stent was devised to open the nasal valve area during anterior mask rhinomanometry. Three groups of subjects were studied with and without the stent. These groups were 1) patients with anatomic findings of nasal valve obstruction, 2) normal control subjects, and 3) normal control subjects with artificially created midseptal nasal obstructions. At peak inspiration the median decrease in resistance with the stent in place when compared to nonstented values was 0.91 Pa.cm-3.s-1 for group 1, 0.27 Pa.cm-3.s-1 for group 2, and 0.25 Pa.cm-3.s-1 for group 3. Comparisons using the nonparametric Wilcoxon test had a significance level of p less than .001. An easily fashioned, well-tolerated nasal valve stent can be readily incorporated in anterior mask rhinomanometry technique. With use of the stent, nasal valve obstruction can be accurately diagnosed and quantitated. PMID- 2310133 TI - Laryngeal granulomatous polyp after short-term intubation of a child. AB - It is well known that prolonged endotracheal intubation may result in formation of laryngeal granulomata. It is rare to find such lesions following short-term intubation. Furthermore, the virtual absence of such granulomata in children has been attributed to certain characteristics of the pediatric larynx. We report a 7 year-old child who developed a laryngeal granulomatous polyp following endotracheal intubation for less than 12 hours. A discussion of the incidence, pathogenesis, and treatment of this and other postintubation laryngeal lesions follows. PMID- 2310132 TI - Approach for oxygenation of the newborn with airway obstruction due to a cervical mass. AB - Large congenital cervical neck masses present major difficulties in management of the neonatal airway at delivery and in the perinatal period. With ultrasound, these lesions can be predicted prenatally. An airway treatment plan can then be formulated and modified in relation to the airway presentation at birth. We describe a case of a massive cervical-mediastinal teratoma and our management plan. Preparation involved a multidisciplinary approach including endoscopy to secure the airway while the neonate remained on fetal circulation and an extracorporeal membrane oxygenation system was available. Once the infant's condition was stable, a cervical approach with resection of the massive teratoma with mediastinal dissection without sternotomy was successful. A differential diagnosis of cervical neck masses and review of cervical teratomas is presented. PMID- 2310134 TI - Experience of a permanent ventilation and drainage system in the management of purulent maxillary sinusitis. AB - Fifty patients with purulent maxillary sinusitis, 11 patients with pressure induced maxillary pain, and 14 patients undergoing maxillary sinus surgery were treated with a new type of permanent ventilation and drainage tube. With use of local anesthesia and as an office procedure, an inferior meatus antrostomy was performed with a circular-bore trephine, and a medical-grade, x-ray-dense silicone tube was inserted to secure the ventilation and drainage. Experience of 14 months of clinical use demonstrated a high success rate (92%) in cases of recurrent and chronic purulent sinusitis. All patients with pressure-induced pain were free from symptoms throughout the observation time. Only a few minor complications were observed. Among the advantages of the method is a more aggressive and early treatment in cases of purulent maxillary infections, possibly prior to the development of irreversible mucosal damage. PMID- 2310135 TI - Surgeons' reported attitudes and practices regarding alaryngeal speech. AB - Attitudes and practices of 50 prominent laryngologic surgeons were surveyed to determine current trends and implications for postoperative speech rehabilitation. Data are available for 1,003 laryngectomy operations performed over the past 3-year period by the 22 responders (44%). Those surgeons responding indicated a preference toward tracheoesophageal shunt procedures. A negative correlation was noted between the increased number of tracheoesophageal shunt procedures and the age of the surgeon. Additional responses provided information regarding personal preferences for postlaryngectomy speech types, opinions regarding artificial device use, and speech rehabilitation referral practices. PMID- 2310136 TI - Daily fluctuations of middle ear pressure in atelectatic ears. AB - The position of the drum of 84 atelectatic ears, of patients 5 to 79 years old, was examined with the help of the operating microscope at different times of the day. All ears were found to be atelectatic during the daytime, yet on the patients' awakening in the morning, 37.73% of the drums of the adolescents' and adults' ears were found to be inflated, usually even hyperinflated. None of the children showed an inflated eardrum in the morning. All eardrums that were inflated in the morning returned to their original atelectatic position within an average of 54.56 minutes after awakening. This observation illustrates another fluctuating aspect of the atelectatic condition. PMID- 2310137 TI - Quantitation of tubotympanal mucociliary clearance in otitis media with effusion. AB - In an attempt to analyze the tubotympanal mucociliary function in otitis media with effusion (OME), human serum albumin labeled with technetium 99m was instilled into 36 ears with effusion and 16 without. The clearance function of the tubotympanum was measured quantitatively. The viscoelasticity of the effusions was measured and was compared with the clearance rate. The clearance rate was significantly lower in ears with effusion than in those without. A significant negative correlation was observed between clearance rate and dynamic viscosity at dynamic viscosities above 2 poise. It is concluded that ears with effusion have significantly lower mucociliary clearance than those without, and that the viscosity of the effusions plays an important role in the mucociliary dysfunction in OME. PMID- 2310138 TI - Morphology of synapses at the base of hair cells in the organ of Corti of the chimpanzee. AB - The synaptic morphology of inner and outer hair cells of the organ of Corti of the chimpanzee was evaluated by serial section electron microscopy. The morphology of nerve terminals and synapses at both sites was very similar to that of human and other mammalian species. Two types of nerve terminals, nonvesiculated and vesiculated, with distinct synaptic morphology were found. In addition, between some nonvesiculated endings and outer hair cells, a reciprocal synaptic relationship was seen. In such terminals there was morphologic evidence for transmission from hair cell to neuron and from neuron to hair cell between a single neuron and an outer hair cell. PMID- 2310139 TI - Fatigue resistance of canine vocal fold muscle. AB - The objective of the experiment was to provide data from dogs, the best nonprimate model for the contractile properties of laryngeal muscles, on the fatigue characteristics of vocal fold muscle. Isometric muscle force was recorded from a transducer attached to the section of the thyroid cartilage on which the muscle inserted. Twitch contractions were recorded during supramaximal indirect electrical stimulation by DC pulses for at least 30 minutes. At 5 pulses per second (p/s), potentiation was observed in all records, peaking at an average of 7.5 minutes after stimulation onset. At 10 p/s, the peak of the potentiated average trace was earlier. One third of these records did not show potentiation. Where moderate or large potentiation was observed, the peak twitch tension declined and reached an asymptote above the initial tension, while when potentiation was small or absent, the final force was smaller than initially. Canine vocal fold muscle was observed to be fatigue-resistant, but in phonation other factors may produce fatigue. PMID- 2310140 TI - Adult rhabdomyoma of the base of the tongue. PMID- 2310141 TI - [A simplified surgical approach in choledochal lithiasis reducing the complexity and severity of this surgery. Study of a series of 153 cases]. AB - The surgical treatment of stones of the common bile duct by transcystic extraction of stones without biliary and peritoneal drainage greatly simplifies biliary surgery. Postoperative course and average hospital stay are similar to those encountered after conventional cholecystectomy. This surgical option was successfully achieved in almost 60% of the 153 patients with stones of the common bile duct of our series, operated between 1981 and 1987. Other patients were treated more conventionally because of failure or impossibility of complete transcystic extraction of stones. A choledochoduodenostomy was performed in 28 patients. In a limited number of patients (n = 12) endoscopic sphincterotomy was associated pre or postoperatively with the surgical treatment. Although 25% of the patients were older than 75 years, there was no operative mortality, which demonstrates that biliary surgery can be performed safely without any vital risk. Successful transcystic extraction of stones simplifies the course of stones of the common bile duct and should be attempt more often. PMID- 2310142 TI - [Laser treatment of rectosigmoid villous tumors. Study of a series of 313 patients]. AB - Endoscopic laser treatment is reported in 313 patients with benign rectosigmoid villous adenomas. Total tumor destruction was achieved in 92% of them, without any major complications. The circumferential extension of the tumor base was the only factor affecting this result. During the average 37-month follow-up period of the patients with total tumor destruction, 14% had a tumor recurrence. The recurrence rate after initial treatment was higher a) in patients treated for a recurrence after a previous non laser treatment, b) when the initial histology was low-grade dysplasia and c) when the tumor was located in the lower or middle rectum. Because treatment is long and difficult with a high cancer rate, laser treatment for patients with a circumferential villous adenoma should be limited to nonsurgical candidates. In the other cases, laser is well adapted to old and fragile patients, when transanal resection seems difficult or in case of recurrence after a previous non-laser treatment. PMID- 2310143 TI - [Crohn disease: results of a series of 42 intestinal resections]. AB - Forty-two patients underwent a resection for acute or chronic complications of Crohn's disease during the years 1983-1987. The colon was involved in 38% (16 patients), the small bowel in 31% (13 patients) and the ileocaecal region in 31%. In small bowel disease, the indication for operation was either an intestinal obstruction or an internal abscess. In colonic locations, poor response to medical therapy was the indication for operation in 10 patients (63%), and an acute complication in the remaining cases. The operations performed were always "radical resections": 13 resections of small bowel, 13 ileocaecal resections, 7 ileocolectomies with ileosigmoidostomies, 6 ileocolectomies with ileorectostomies, 2 left side hemicolectomies with colorectostomies and one total coloproctectomy. There was no operative mortality. A post-operative complication occurred in two patients (4.8%). The recurrence rate was 12% after 30 months average follow up in the 34 patients with only one operation for Crohn's disease. There was no second recurrence in the 8 patients operated for a first recurrence. The factors affecting recurrence after resection were: a short pre-operative time interval since first clinical symptoms: 4.6 years versus 5.3 years without recurrence (p less than 0.01); the colonic location of the Crohn's disease (p less than 0.02). Colonic location rate of the disease was found to be higher in this study as compared to others. Since "radical resection" fails to cure all patients, surgery should be restricted to acute on chronic complications. PMID- 2310144 TI - [Sigmoid diverticular pathology. Apropos of a homogeneous series of 82 cases]. AB - The authors report a retrospective series of 82 cases of sigmoid diverticulosis which revealed the following points: surgery is rarely performed on "cold" disease but for acute or chronic complications, diverticular disease is very often present for a very long time and the doctor or the patient has refused operation for various reasons, whenever possible, infection must be eradicated as first line treatment and continuity must be restored under protection of a right transverse colostomy which is closed 4 to 6 weeks later. The authors prefer this approach to Hartmann's operation, in which the restoration of colonic continuity appears to be more delicate and which tends to prevent the surgeon from performing a sufficiently low inferior section, the source of poor long-term results. There was no postoperative mortality in this series, which may be due to the special environment in which surgery was performed. It is preferable to operate patients with "cold" diverticulosis before the development of complications, which allows simpler one-stage surgery requiring a shorter and therefore less expansive hospital stay. PMID- 2310145 TI - [Injury of the azygos vein. A new complication of upper digestive endoscopy]. AB - A patient presented with a ruptured azygos vein following esophagoscopy. The diagnosis was difficult. Selective angiography was helpful and surgical treatment ensured good result. This is the first case of this type to be reported in the literature. PMID- 2310147 TI - [Surgical indications in pancreatic pseudocysts]. PMID- 2310146 TI - [Pulmonary metastasis with left intra-atrial extension of liposarcoma. Apropos of a case]. AB - The direct extension of a neoplastic thrombus of the pulmonary veins into the left atrium is extremely rare. The authors report the case of a pulmonary metastasis from a liposarcoma of the thigh extending into the pulmonary veins and prolapsing into the left atrium. The patient was successfully treated by tumorectomy under cardiopulmonary bypass then by left upper lobectomy. PMID- 2310148 TI - [Endoscopic treatment of pancreatic cysts and pseudocysts]. PMID- 2310149 TI - [The role of interventional radiology in the treatment of pancreatic pseudocysts]. PMID- 2310150 TI - A new interpeduncular screw fixation system: biomechanics, radiologic appearances and complications of the Steffee spine-plate implant. AB - A newly developed spinal fixation system, designed to assist spinal fusion, is described and case histories are reported to illustrate some radiologic appearances and complications. The biomechanical concepts underlying its use are briefly presented, with the advantages of transpeduncular fixation being emphasized. PMID- 2310151 TI - [Lymphadenectomy in the treatment of intrathoracic esophageal cancer. A series of 240 cases]. PMID- 2310152 TI - Distribution of haemoglobin in patients presenting to their general practitioner, and its correlation with serum ferritin. AB - We have conducted a survey in the United Kingdom in order to evaluate the prevalence of anaemia and of iron deficiency in elderly male and female patients and in female patients of child-bearing age presenting to their general practitioner. Although haemoglobin values were approximately normally distributed, there was evidence of a bimodal distribution of serum ferritin values, particularly in elderly men. A correlation between serum ferritin and haemoglobin values was found to exist, both in the elderly and in younger women. The overall prevalence of anaemia in the study population was 14.3%, although it was higher for elderly men (20.1%) than either elderly women (13.7%) or women of child-bearing age (11.9%). Iron deficiency associated with anaemia was more common in elderly men (45.2% of those anaemic) than elderly women (28.6%) or women of child-bearing age (25.6%). This survey indicates that the prevalence of anaemia among certain groups of high risk patients presenting for consultation to their general practitioner is about 1 in 7, although the prevalence is as high as 1 in 5 in elderly men. PMID- 2310153 TI - Urinary aluminium excretion following renal transplantation and the effect of pulse steroid therapy. AB - Urinary aluminium was measured in 48 patients with primary graft function for 14 days following renal transplantation. The plasma aluminium prior to transplantation was greater in those prescribed aluminium-containing phosphate binders (1.7 +/- 0.2 vs 0.6 +/- 0.2 mumol/L, P less than 0.05) and correlated with the duration of dialysis therapy (r = 0.42, P less than 0.008). After an initial reduction the plasma aluminium returned to pre-transplant values by the fifth day. The 24 h urinary aluminium excretion, aluminium clearance and fractional aluminium excretion all increased during the first week to a maximum around the sixth postoperative day, thereafter returning to values obtained during the first postoperative days, suggesting an early 'wash-out' of a readily accessible aluminium pool followed by a lower steady state determined by the rate of release of aluminium from tissue stores. For the whole group, aluminium excretion, at this steady state, was five times that of urinary aluminium excretion in normal subjects. Acute allograft rejection was diagnosed in 25 patients, who were treated with pulsed methyl prednisolone. Apart from improving graft function, no additional effect was observed on aluminium excretion, suggesting that the readily accessible aluminium pool does not come from lysosomal release, but probably from aluminium bound to small molecular weight protein. PMID- 2310154 TI - Serum prolactin bioactivity and immunoactivity in hyperprolactinaemic states. AB - Serum prolactin concentrations were measured using a sensitive bioassay (Nb2 assay) and by radioimmunoassay in 11 patients with prolactin-secreting pituitary tumours (median serum immunoactive prolactin 5150 mU/L), and in 58 normal control subjects (median prolactin 190 mU/L). The mean ratio of serum prolactin bioactivity to immunoactivity was significantly lower in patients with prolactinomas than in normoprolactinaemic controls. Ten lactating women in the early post-partum period (median prolactin 3800 mU/L), studied as a model of physiological hyperprolactinaemia, also had reduced bioactivity to immunoactivity ratios. Overall, there was a significant negative correlation between bioactivity:immunoactivity ratio and serum immunoactive prolactin. The change in relative bioactivity of prolactin in serum samples from patients with prolactinomas and in women with physiological hyperprolactinaemia may reflect changes in the molecular heterogeneity of the hormone. Such changes may affect activity in both bioassays and radioimmunoassays. PMID- 2310155 TI - Colorimetric glucose assay using thermostable glucokinase. AB - A method for assaying glucose in serum or plasma samples using a thermostable glucokinase was developed. Glucokinase from Bacillus Stearothermophilus was coupled with glucose-6-phosphate dehydrogenase to produce NADPH, which reduced the tetrazolium dye MTT to its formazan. Detection of the product at 660 nm allowed samples containing up to 30 mmol/L glucose to be assayed with an endpoint method. Use of the optimal wavelength for formazan detection, 570 nm, increased sensitivity for NADPH detection by over threefold compared to UV detection. The stability of glucokinase assay mixtures was extensively studied, with variation in buffers, salt and enzyme stabilizers. Maximal half life for reagent stability at room temperature was approximately 30 days, with storage of assay mixtures in two solutions. Various drugs and metabolites were tested for interference in the method and no significant interferences were found. PMID- 2310156 TI - Erythrocyte membrane stearic acid: oleic acid ratios in colorectal cancer using tube capillary column gas liquid chromatography. AB - Erythrocyte fatty acids were measured in 32 patients with colorectal cancer (four with recurrent disease), four patients with large colorectal adenomas, and 42 hospitalised patients without cancer. No significant differences were found with respect to any of the fatty acids between these groups. In particular there was no difference between the erythrocyte stearic acid: oleic acid ratios (mean +/- SD) between the cancer cases (1.07 +/- 0.31) and the control cases (1.09 +/- 0.31, 2-tailed Mann-Whitney U test). No difference in this ratio was observed with respect to age or sex and in the case of colorectal cancer, to the Dukes' stage, degree of tumour differentiation, or recurrence. A significant correlation was found between stearic acid concentrations in plasma and erythrocytes from fasting individuals (r = 0.477, n = 24, P less than 0.05). This study provides further evidence that the erythrocyte stearic acid: oleic acid ratio is of no value for diagnosing primary or recurrent colorectal cancer. PMID- 2310157 TI - Mucosal digestion studies of whole gliadin fractions in coeliac disease. AB - Wheat gliadin was chromatographed on carboxymethyl cellulose and the major fractions (alpha-, beta- and gamma-gliadin) digested with pepsin, trypsin and pancreatin. The digests from each fraction were chromatographed on SP Sephadex and the fractions corresponding to the one previously shown to be toxic by oral feeding tests (fraction 9) were incubated with homogenates of small intestinal mucosa from children with coeliac disease in remission and from normal children. Electrophoretic patterns of the coeliac mucosal digests of fraction 9 from the alpha-, beta- and gamma-gliadin fractions all showed that appreciable amounts of undigested peptides were present in each of the three digests. In contrast, patterns of all digests prepared using normal mucosa showed only small amounts of undigested peptides. The results suggest that all three of these whole gliadin fractions contain substances which may be causative agents in coeliac disease. PMID- 2310158 TI - Modification to a commercial immunoradiometric assay permitting intraoperative monitoring of parathyroid hormone levels. AB - We describe a modification to a commercially available immunoradiometric assay which reduces the turnaround time for parathyroid hormone (PTH) measurement to 1 h and permits intraoperative monitoring during parathyroidectomy. Alterations in PTH concentrations following removal of parathyroid tissue are compared with those of calcium, ionised calcium and phosphate. PTH measurements obtained intraoperatively permit definitive conclusions about the success of the operation within 1 h of sampling, allowing re-exploitation of the gland to take place immediately if necessary. PMID- 2310159 TI - Immunoradiometric assay for intact human parathyroid hormone: characteristics, clinical application and comparison with a radio-immunoassay. AB - Circulating immunoreactive intact human parathyroid hormone (PTH) was measured by a direct immunoradiometric assay (IRMA) and the results compared with a radio immunoassay (RIA) which required extraction and concentration prior to assay. The sensitivity of the IRMA was better than that of the RIA (0.6 vs 2.0 pmol/L). In control subjects the hPTH concentrations ranged between 0.6 and 6.7 pmol/L and in patients with hypercalcaemia due to malignant diseases, sarcoidosis and hypoparathyroidism none could be detected. In patients with primary hyperparathyroidism the concentrations ranged from 5.2 to 27.0 pmol/L. In patients with renal osteodystrophy serum human PTH concentrations ranged from 7.6 to 285 and in those with chronic renal failure but without evidence of renal osteodystrophy from 0.5 to 5.2 pmol/L. The major advantages of the IRMA are its much simpler performance and its higher sensitivity which makes studies of the physiology of PTH secretion in humans possible. PMID- 2310160 TI - Effect of delay in separating plasma for glucose measurement upon the interpretation of oral glucose tolerance tests. PMID- 2310161 TI - Predictive value of D-xylose absorption test and erythrocyte folate in adult coeliac disease: a parallel approach. PMID- 2310162 TI - Ferrochelatase activity in human lymphocytes: effect of storage on haem formation. PMID- 2310164 TI - Are the positive interferences in the benzethonium chloride method for urine protein real? PMID- 2310163 TI - Congenital hypothyroidism with spuriously increased FT3 concentrations in infant and mother. PMID- 2310165 TI - Can we measure C-reactive proteins? PMID- 2310166 TI - Serum protein electrophoresis: Italian survey 1986. PMID- 2310167 TI - Lack of effect of overnight storage of heparinised blood at 4 degrees C on plasma phosphate concentration. PMID- 2310168 TI - Hirsutism: free and bound testosterone. PMID- 2310169 TI - Diagnostic pitfalls in the diagnosis of soft tissue bladder tumors in pediatric patients. AB - This is a case report of a low-grade leiomyosarcoma of the bladder in a four-year old girl. The pitfalls in diagnosing a soft tissue tumor of the bladder in pediatric patients are discussed. This case is particularly instructive because the differential diagnosis was broad, difficult, and of serious consequence. This report discusses the process by which histologic, immunohistologic and ultrastructural data were used to sidestep the pitfalls in diagnosing this unusual tumor. Clinical follow-up data bearing out our conclusion are also presented. PMID- 2310170 TI - Trace element status in alcoholism before and during disulfiram treatment. AB - Trace element status was ascertained in 19 alcoholic patients under long-term treatment with disulfiram and in 12 alcoholic patients treated for the first time; the latter group was re-examined after four weeks of treatment. Both groups were compared to matched controls with a moderate alcohol intake. The copper/zinc ratio in serum was increased in the patients under long-term treatment, and a significant decrease occurred during the first four weeks of treatment in the second group. Blood lead was slightly increased in the second group, but not in the patients under long-term treatment. Blood cadmium was high in both groups, perhaps related to excessive tobacco smoking. Blood mercury concentrations were uniformly low. Urinary nickel excretion in the first group was above reference values, and an increase was seen in the second group during the treatment period. Although trace element concentrations in body fluids may not reflect tissue levels, the results support the notion that trace element balances are influenced by alcoholism and disulfiram treatment. PMID- 2310171 TI - Chromosomal abnormalities and gene amplification in renal cancers induced in rats by nickel subsulfide. AB - Nickel subsulfide (alpha Ni3S2) was administered to male Fischer-344 rats by unilateral intrarenal (i.r.) injection (20 mg per rat) to establish the time course of alpha Ni3S2-induced erythrocytosis and to identify chromosomal abnormalities and molecular genetic aberrations in ensuing renal cancers. Blood hematocrit values were increased in alpha Ni3S2-treated rats during two to 36 weeks post-injection, attained a maximum of 77 percent (SD +/- 5) at 16 weeks (vs 51 +/- 3 percent in vehicle controls), and returned to baseline at 40 weeks. Within 21 months, malignant neoplasms (five sarcomas, one carcinoma) occurred in the injected kidneys of 6/28 alpha Ni3S2-treated rats (vs 0/13 controls). Cytogenetic analyses of direct preparations or primary cell cultures showed prominent chromosomal aberrations in three neoplasms, with rearranged marker chromosomes, polyploidy, and in one case an homogeneously staining region (HSR). Assays for gene amplification were performed with probes for murine erythropoietin (EPO) gene and H-ras, c-fos, c-myc, and N-myc oncogenes, using deoxyribonucleic acid (DNA) samples isolated from injected kidneys and renal neoplasms, as well as from the contralateral, non-injected kidneys. No consistent pattern was found; in one sarcoma, N-myc was amplified six-fold and c-fos was amplified two-fold; in another sarcoma, H-ras, c-fos, and EPO were amplified two fold. This study shows that (a) karyotypes of 3/6 renal neoplasms of alpha Ni3S2 treated rats contained prominent marker chromosomes, (b) oncogene amplification was noted in 2/6 renal neoplasms, and (c) the EPO gene was not consistently amplified in DNA from the injected kidneys of alpha Ni3S2-treated rats during the initiation of erythrocytosis, or in subsequent renal neoplasms. PMID- 2310173 TI - Impaired platelet function associated with parenteral nafcillin. AB - A 44-year-old Caucasian female was admitted with a subarachnoid hemorrhage owing to a multilobular tubular anterior communicating artery aneurysm. Eleven days after the original craniotomy, an epidural hematoma was evacuated. The patient was placed on empiric nafcillin antimicrobial coverage (two g every six hours). Within 24 hours, the onset of epistaxis and oozing of blood from the endotracheal tube and craniotomy site was noted. Recurrent subdural and epidural hematomas necessitated a third emergent craniotomy. The development of an acquired qualitative platelet defect was suggested by the findings of a prolonged template bleeding time and markedly abnormal platelet aggregation/ATP release studies despite a normal platelet count. Nafcillin therapy was immediately discontinued. Clinical bleeding resolved. Subsequent bleeding times and platelet aggregation studies confirmed the nafcillin-induced platelet dysfunction. PMID- 2310172 TI - A comparison of two macroscopic platelet agglutination assays for von Willebrand factor. AB - Plasma drawn from 22 patients with a broad range of von Willebrand factor (vWF) levels, including one patient with rare, severe type III von Willebrand's disease, was used to investigate the adaptability of the Bio/Data Corp. vW Factor Assay, a ristocetin cofactor-based kit developed for use with a platelet aggregometer, to a macroscopic platelet agglutination technique. The results were compared to those obtained using the General Diagnostics von Willebrand Factor Assay, another ristocetin cofactor-based kit developed for use as a macroscopic platelet agglutination procedure. No significant difference (p greater than 0.5) existed between results obtained by these two kits. The mean and standard deviation of the vWF levels (as percent of normal) were 132 +/- 66.7 by the General Diagnostics kit and 133 +/- 59.0 by the Bio/Data Corp. kit. The correlation coefficient (r) was 0.81. The Bio/Data Corp. kit is more costly per test than the General Diagnostics kit. However, it was shown to be compatible with the macroscopic agglutination technique and required no modification to be used in that manner. PMID- 2310174 TI - Choosing a beverage: comparison of preferences and beliefs related to the reported consumption of regular vs. diet sodas. AB - In a survey conducted among American females (N = 100, mean age = 20.8 years), consumption of regular and diet sodas and related beliefs and concerns were measured. Based on reported frequencies of consumption, 30 could be classified as users of regular and 44 as users of diet sodas, while 20 subjects did not use either. Both user groups reported liking for their "own" sodas and dislike for the "other" sodas, and non-users did not like either. Beliefs best differentiating among the three groups were: (1) superiority of taste of their "own" sodas, (2) perceived efficiency to quench thirst, and (3) perceived compatibility with other menu items. Users of diet sodas and the non-users were more concerned about weight-related issues than users of regular sodas, who had less concerned attitudes. The users of regular sodas also reported a significantly higher frequency of consumption of several foods high in sugar, fat and/or sodium. Thus, the selection of one's principal soda is not only a choice between two beverages but may be an indication of a particular consumption style and reflect a whole set of attitudes towards one's own body. PMID- 2310175 TI - Effects of food snacks on cognitive performance in male college students. AB - The effects of food snacks consumed in the late afternoon on cognitive performance in college-aged men were investigated in two experiments. The effects of the snacks were tested in the same subjects after they either consumed or skipped lunch. In the first experiment, the calorie-rich snack was a confectionery product, while in the second experiment, the snack was fruit flavored yogurt. In both experiments, performance on cognitive tasks following consumption of the calorie-rich snack was compared to performance following consumption of a very low calorie snack (lemon-lime flavored diet soda without caffeine). Four cognitive tasks were employed: digit span recall (forward and backward), arithmetic reasoning, reading, and attention. In both experiments, subjects recalled significantly more digits in the backward digit span test and responded significantly faster in the attention task when they had consumed the calorific snack than when they had consumed the diet soft drink. Additionally, in Experiment 2, subjects solved significantly more arithmetic problems and solved these problems in significantly less time after eating a fruit-flavored yogurt than after consuming the diet soft drink. Results of these experiments suggest that a late afternoon energy-containing snack can have positive effects on cognitive performance on tasks that require sustained attention. PMID- 2310176 TI - Flavor preferences and fructose: evidence that the liver detects the unconditioned stimulus for calorie-based learning. AB - Previous work suggests that fuel oxidation in the liver provides an unconditioned stimulus for "calorie-based" flavor preference learning. To investigate this possibility in more detail, we manipulated liver metabolism by taking advantage of the greater specificity to the liver of fructose than glucose. Intact rats preferred flavored food ingested with a drink of 35% fructose solution to flavored food eaten with either no sweet drink (Experiment 1) or an equicaloric drink of glucose (Experiment 2). The effect on food preference did not depend on the taste of the sugar solutions: when given a choice between glucose and fructose solutions, the rats drank the same volume of each. Moreover, a preference for fructose-paired flavored food was obtained when fructose and glucose solutions were given by gavage (Experiment 3). Unlike intact rats, rats with hepatic vagotomy preferred equally flavored food paired with fructose solution and flavored food paired with no sugar solution (Experiment 1). They also avoided flavored food paired with gavage of fructose slightly, relative to flavored food paired with gavage of glucose (Experiment 3). These results suggest that the unconditioned stimulus for calorie-based conditioning is transduced in the liver, and that an intact hepatic vagus nerve is required for conditioning to occur. PMID- 2310177 TI - Development of eating behavior and its relation to physical growth in normal weight preschool children. AB - In order to examine whether some characteristics of eating behavior are related to physical growth and weight increment in young children, a longitudinal prospective study was conducted. The eating behaviors of 11 age-matched normal weight preschool children were observed at lunchtime on 18 consecutive days. The same set of observations was carried out three times when the children were 40, 52 and 59 months old, on average. MANOVA procedures for repeated measures design revealed that the eating behavior of the subjects changed considerably between the first and second observation stages, whereas it did not change significantly between the second and third stages. It was considered that eating behaviour developed mostly between the first and second observation stages and that the subjects were able to eat completely independently by the second observation stage. The increment in the children's weight per month began to show individual variation at the age of 48 months between the first and second observation stages. Coincidentally, the relationship between eating behavior and physique first appeared at the second observation stage and a similar relationship was observed at the third stage. The partial correlation coefficients and the multivariate multiple regression of MANOVA were performed for this analysis. Meal duration was the factor most strongly related to weight and BMI, whereas in contrast, growth history and familial factors influenced the eating behavior at the first observation stage. The present results indicate that eating behavior was one of the factors related to the rapid increase in weight soon after or just at the time of initiation of complete self-feeding in normal-weight children. PMID- 2310178 TI - Differences in food-choice frequencies between restrained and unrestrained eaters. AB - Reported frequency of consumption for certain food items was studied in young normal-weight women, classified into 19 unrestrained and 20 restrained eaters by the Three-Factor Eating Questionnaire of Stunkard & Messick (1985). Neither group differed in the consumption of basic foods and snacks but restrained eaters showed a strong tendency to avoid fat. A large percentage of this group was used to consuming artificial sweeteners and other calorie-reduced foodstuffs. These qualitative alterations in the everyday eating behavior of restrained eaters may be one of the links between dietary restraint and binge eating. PMID- 2310179 TI - A synthetic oligonucleotide probe and a cloned polynucleotide probe based on the yopA gene for detection and enumeration of virulent Yersinia enterocolitica. AB - We compared a synthetically produced 19-mer oligonucleotide probe with a polynucleotide probe consisting of a cloned fragment of the virulence gene yopA for their relative efficiencies in identification and enumeration of virulent Yersinia enterocolitica. The probes were used in DNA-DNA colony hybridization assays to differentiate 70 Yersinia strains with known plasmid profiles. All 19 strains harboring the 40- to 50-megadalton virulence plasmid were positive in the hybridization assay, whereas their isogenic derivatives lacking this plasmid were negative. Both probes correctly identified plasmid-bearing variants of Y. enterocolitica serogroups O:3, O:5,27, O:8, O:9, O:13, and O:21 from three continents. In contrast, none of the probes hybridized with DNA from 32 environmental yersiniae belonging to 26 serogroups not associated with disease. Colony hybridization was used to detect and enumerate virulent Y. enterocolitica in three artificially contaminated food samples. Despite a large background of indigenous bacteria (3 x 10(4) CFU), the efficiency of enumeration ranged from 33 to 82%. The use of nylon filters did not impair the growth of virulent yersiniae. Both probes showed a perfect concordance in their specific differentiation and enumeration of virulent Y. enterocolitica. DNA colony hybridization with these two probes permitted rapid and reliable identification of all common pathogenic serogroups without the need for enrichment or esoteric identification protocols. PMID- 2310180 TI - Development and application of oligonucleotide probes for molecular identification of Xenorhabdus species. AB - Synthetic deoxyoligonucleotide probes that hybridized against the region at positions 455 through 480 of 16S rRNA were developed for the identification of all five Xenorhabdus species. Sequence variation in the respective rRNA region between two strains of Xenorhabdus luminescens in addition allowed the construction of two strain-specific probes. Of 27 isolates determined to be Xenorhabdus strains by phenotypic characterization, 24 could be assigned to four of the five species. Two strains (HL-1 and HL-2) isolated from a Heterorhabditis sp. and a single strain (D-1.1) isolated from Steinernema affinis showed no hybridization signal with any of the five species-specific probes. With regard to the available species descriptions of nematodes, the results presented here confirm that, except for Steinernema affinis, the individual nematode hosts harbor only a single Xenorhabdus species. PMID- 2310181 TI - Isoverrucarol production by Fusarium oxysporum CJS-12 isolated from corn. AB - Isoverrucarol (3,15-dihydroxy-12,13-epoxy-trichothec-9-ene) was isolated and purified from wheat cultures of a toxic strain of Fusarium oxysporum CJS-12. The toxin was characterized by thin-layer chromatography, gas chromatography-mass spectrometry, and 1H and 13C nuclear magnetic resonance spectrometry. Isoverrucarol caused toxic effects in rats, including loss of appetite, bodily weakness, severe mucosae of the stomach, and death, when administered orally at 10 and 20 mg/kg of body weight. The toxin also caused a definite dermatitic reaction of epidermis and an edematic-necrotic response of the dermis. PMID- 2310182 TI - Model for inactivation and disposal of infectious human immunodeficiency virus and radioactive waste in a BL3 facility. AB - A method is described for autoclaving low levels of solid infectious, radioactive waste. The method permits steam penetration to inactivate biologic waste, while any volatile radioactive compounds generated during the autoclave process are absorbed. Inactivation of radiolabeled infectious waste has been problematic because the usual sterilization techniques result in unacceptable radiation handling practices. If autoclaved under the usual conditions, there exists a high probability of volatilization or release of radioisotopes from the waste. This results in the radioactive contamination of the autoclave and the laboratory area where steam is released from the autoclave. Our results provide a practical method to inactivate and dispose of infectious radioactive waste. For our research, Bacillus pumilus spore strips and vaccinia virus were used as more heat resistant surrogates of the human immunodeficiency virus (HIV). These surrogates were used because HIV is difficult to grow under most conditions and is less heat tolerant than the surrogates. In addition, B. pumilus has defined cell death values, whereas such values have not been established for HIV. Both B. pumilus and vaccinia virus are less hazardous to work with. The autoclave method is time efficient and can be performed by laboratory personnel with minimal handling of the waste. Furthermore, waste site handlers are able to visually inspect the solid waste containers and ascertain that inactivation procedures have been implemented. PMID- 2310184 TI - New plate medium for facilitated differentiation of Salmonella spp. from Proteus spp. and other enteric bacteria. AB - A new agar medium for the differentiation of Salmonella spp. from other members of the family Enterobacteriaceae is described. This medium exploits a novel phenotypic characteristic of Salmonella spp.: the formation of acid from propylene glycol. This characteristic may be used in combination with a chromogenic indicator of beta-galactosidase to differentiate Salmonella spp. from Proteus spp. and the other members of the Enterobacteriaceae. Desoxycholate may be included in the plate medium as an inhibitor of gram-positive organisms. Non typhi Salmonella spp. yield distinct, bright red colonies on this medium, allowing facilitated identification and unambiguous differentiation from Proteus spp. PMID- 2310183 TI - New pathway for the biodegradation of indole in Aspergillus niger. AB - Indole and its derivatives form a class of toxic recalcitrant environmental pollutants. The growth of Aspergillus niger was inhibited by very low concentrations (0.005 to 0.02%) of indole, even when 125- to 500-fold excess glucose was present in the medium. When 0.02% indole was added, the fungus showed a lag phase for about 30 h and the uptake of glucose was inhibited. Indole was metabolized by a new pathway via indoxyl (3-hydroxyindole), N-formylanthranilic acid, anthranilic acid, 2,3-dihydroxybenzoic acid, and catechol, which was further degraded by ortho cleavage. The enzymes N-formylanthranilate deformylase, anthranilate hydroxylase, 2,3-dihydroxybenzoate decarboxylase, and catechol dioxygenase were induced by indole as early as after 5 h of growth, and their activities were demonstrated in a cell-free system. PMID- 2310185 TI - Organomercurial-volatilizing bacteria in the mercury-polluted sediment of Minamata Bay, Japan. AB - A total of 4,604 bacterial strains isolated from the sediments of Minamata Bay and nearby low-level-mercury stations (control stations) were screened for the ability to volatilize mercury from inorganic and organic mercurial compounds. The strains that volatilize mercury from several kinds of organomercurials were found only in the sediments of Minamata Bay. PMID- 2310186 TI - Supernatant protein and cellulase activities of the anaerobic ruminal fungus Neocallimastix frontalis EB188. AB - Protein and cellulose activities were measured in culture supernatants of the anaerobic ruminal fungus Neocallimastix frontalis EB188 established in glucose medium and switched to either glucose, cellobiose, or cellulose media. Polyacrylamide gel electrophoresis was used to show differences caused by changing medium carbon source. Culture supernatants contained proteins with molecular weights ranging from greater than 116,000 to about 19,000. Low levels of cellulose activity were evident in glucose-grown cultures. Increased amounts of slowly migrating cellulase activities appeared in the supernatants of glucose grown cultures switched to cellulose. Cellulase activities which reacted differentially during colorimetric and in situ assays were produced. Isoelectric points of cellulase activities varied from 3.7 to 8.3, and activities possessed optimal pHs of between 5.9 and 6.5. PMID- 2310187 TI - Differential effects of sodium on hydrogen- and glucose-dependent growth of the acetogenic bacterium Acetogenium kivui. AB - Acetogenium kivui could not be revived or maintained in a sodium-deficient medium (0.2 mM sodium) under H2-dependent conditions, and neither lithium nor potassium replaced the sodium requirement of H2-cultivated cells. Conversely, the revival and maintenance of glucose-cultivated cells did not display a dependency on supplemental sodium. In the absence of growth, formate became a major end product in both sodium-deficient and metabolically impaired H2-grown cultures of A. kivui. Harmaline, a putative inhibitor of Na+/H+ antiporters, uncoupled acetogenesis from H2-dependent growth but was less effective when growth was at the expense of glucose. Significantly, carbon monoxide (CO) stimulated H2 dependent growth of A. kivui but inhibited glucose-dependent growth. Collectively, these findings demonstrate that sodium plays a critical role in the H2-dependent bioenergetics of A. kivui and indicate that autotrophic and heterotrophic cells may utilize dissimilar mechanisms of energy conservation. In contrast to the growth of A. kivui, supplemental sodium was not required for the glucose-, H2-, and CO-dependent growth of Clostridium thermoaceticum. PMID- 2310188 TI - Efficiency of bacterial protein synthesis during anaerobic degradation of cattle waste. AB - The rate of [15N]ammonia (15NH3) uptake or incorporation into bacterial cells was studied, using stirred, 3-liter benchtop digestors fed on a semicontinuous basis with cattle waste. The fermentations were carried out at 40 and 60 degrees C and at four different loading rates (3, 6, 9, and 12 g of volatile solids per liter of reactor volume per day). The rate of NH3-N incorporation for the period 1 to 5 h after feeding at the four different loading rates was 0.49, 0.83, 1.05, and 1.08 mg/liter per h in the mesophilic digestor and 0.68, 1.07, 1.17, and 1.21 mg/liter per h in the thermophilic digestor. Values were lower 7 to 21 h after feeding in both digestors and were related to the rate of fermentation or CH4 production. In the mesophilic digestors, the rate of bacterial cell production ranged from 3.97 to 8.72 mg of dry cells per liter per h, 1 to 5 h after feeding at the different loading rates. Corresponding values for the thermophilic digestors ranged from 5.46 to 9.77 mg of dry cells per liter per h. Cell yield values ranged from 2.3 to 3.1 mg of dry cells per mol of CH4 produced in the mesophilic and thermophilic digestors at the two lower loading rates. The values were higher (2.8 to 3.4) in the mesophilic digestors at the two higher loading rates because of the accumulation of propionate and a consequent reduction in CH4 production. Low cell yields such as those measured in this study are characteristic of low-specific-growth rates under energy-limited conditions. PMID- 2310189 TI - Possible mechanism of mannose inhibition of sucrose-supported growth in N2-fixing Azotobacter vinelandii. AB - When mannose was added to a sucrose-supported culture of Azotobacter vinelandii under N2-fixing conditions, cell growth was inhibited. The degree of inhibition was proportional to the amount of mannose and to the aeration rate (T.-Y. Wong, Appl. Environ. Microbiol. 54:473-475, 1988). In this report, we demonstrate that once inside the cell, mannose was phosphorylated to mannose 6-phosphate. It was then isomerized to fructose 6-phosphate and to glucose 6-phosphate. Mannose inhibited sucrose uptake noncompetitively. The decrease in sucrose uptake after mannose addition coincided with a lower rate of respiration and a decrease in nitrogenase activity. The decrease in sucrose uptake and in the ATP pool may decrease the electron flow and reduce protection of the nitrogenase from O2. Cells became very sensitive to O2, and therefore, cell growth was inhibited under high aeration conditions. PMID- 2310190 TI - Characterization of molecular species of liver microsomal carboxylesterases of several animal species and humans. AB - Seven carboxylesterase isozymes were purified to electrophoretic homogeneity from liver microsomes of mouse, hamster, guinea pig, rabbit, and monkey by the same procedure used previously to obtain three isozymes from the rat, and their physical, enzymological, and immunological properties were compared with those of the rat isozymes. The substrate specificity and immunological reactivity of liver microsomal carboxylesterases from pig, cow, beagle dog, and human were also examined for comparison, though these enzymes were not purified. The ten purified preparations have similar subunit weight (57,000-64,000), but their isoelectric points differ widely (4.7-6.5). The purification procedure of all isozymes included concanavalin A-Sepharose column chromatography. The isozymes were not eluted from the column with a high concentration of sodium chloride, but were efficiently eluted with alpha-methylmannoside. This observation suggested that the carboxylesterases studied are glycoproteins. All the isozymes except rat RL1 and RL2 possess a high hydrolytic activity toward all the substrates examined. Long-chain monoglyceride was hydrolyzed by the purified carboxylesterase isozymes. Anti-rat RH1 immunoglobulin G was found to possess high cross reactivity with all isozymes tested, except monkey MK2, by immunoblotting analysis. The amino acid compositions of carboxylesterase isozymes showed considerable similarities, except for monkey MK2. The amino-terminal amino acid sequences showed a striking homology, except for monkey MK2, though the amino terminal amino acid itself was different in every isozyme. Hepatic microsomal carboxylesterases in mammals play an important role in drug and lipid metabolism in the endoplasmic reticulum, and it is noteworthy that the isozymes from various species examined here showed considerable similarities in physical, enzymatic, and immunochemical properties. PMID- 2310191 TI - Alteration of aminoacyl-tRNA synthetase with age: heat-labilization of the enzyme by oxidative damage. AB - Active oxygens have been suggested to be involved in age-related alterations of organelles and molecules. In this study we investigated the influence of active oxygen on aminoacyl-tRNA synthetases partially purified from rat liver. Treatment of leucyl-tRNA synthetase with Fe3(+)-ascorbate resulted in the increased heat lability of the enzyme. The inactivation was inhibited by radical scavengers such as mannitol and benzoate, suggesting that hydroxyl radicals are responsible for heat-labilization of the enzyme. On the other hand, a considerable part of tyrosyl-tRNA synthetase was converted to heat-labile forms without added iron and ascorbate under aerobic conditions but not under anaerobic conditions. These and other findings suggested that the heat-labilization of this enzyme is caused by active oxygens probably generated by the reaction of dioxygen and transition metal ions present in the enzyme preparations. Heat-inactivation curves of the enzymes modified as described above were similar to those observed for the enzymes from aged animals in that these enzymes exhibited higher percentages of heat-labile forms than the unmodified enzymes from young animals [Takahashi and Goto, 1987, Arch. Gerontol. Geriatr. 6, 73-82; Takahashi and Goto, 1987, Arch. Biochem. Biophys. 257, 200-206]. The present findings are consistent with the theory that active oxygens are involved in the age-related alterations of enzymes. PMID- 2310192 TI - Modeling of the electrostatic potential field of plastocyanin. AB - The DelPhi computer program is used to calculate the electrostatic potential field of the photosynthetic electron transport protein plastocyanin. Knowledge of the potential field is important for understanding the mechanisms by which plastocyanin interacts with other charged reagents. The program uses a macroscopic, continuum approach in which the protein and solvent are assigned different dielectric constants, the crystal structure of the protein defines the dielectric boundary, and the ionic strength of the solvent is taken into account. The potential field is determined by numerically solving the Poisson-Boltzmann equation. The field surrounding plastocyanin is characterized by a region of positive potential over the copper center active site, and a region of negative potential over the adjacent association site containing tyrosine 83. The shape and magnitude of the potential field shows a strong dependence on the ionic strength and pH of the solvent. The program is able to accurately predict the effect of the copper center oxidation state on the pKa of a tetranitromethane derivative of tyrosine 83 using an intrinsic protein dielectric constant of 2 to 4. Evidence is also presented that the glutamate 68 side chain is exposed to the solvent to a greater extent in the solution structure of plastocyanin than in the crystal structure. PMID- 2310194 TI - NADPH- and adriamycin-dependent microsomal release of iron and lipid peroxidation. AB - In a previous study (Minotti, G., 1989, Arch. Biochem. Biophys. 268, 398-403) NADPH-supplemented microsomes were found to reduce adriamycin (ADR) to semiquinone free radical (ADR-.), which in turn autoxidized at the expense of oxygen to regenerate ADR and form O2-. Redox cycling of ADR was paralleled by reductive release of membrane-bound nonheme iron, as evidenced by mobilization of bathophenanthroline-chelatable Fe2+. In the present study, iron release was found to increase with concentration of ADR in a superoxide dismutase- and catalase insensitive manner. This suggested that membrane-bound iron was reduced by ADR-. with negligible contribution by O2-. or interference by its dismutation product H2O2. Following release from microsomes, Fe2+ was reconverted to Fe3+ via two distinct mechanisms: (i) catalase-inhibitable oxidation by H2O2 and (ii) catalase insensitive autoxidation at the expense of oxygen, which occurred upon chelation by ADR and increased with the ADR:Fe2+ molar ratio. Malondialdehyde formation, indicative of membrane lipid peroxidation, was observed when approximately 50% of Fe2+ was converted to Fe3+. This occurred in presence of catalase and low concentrations of ADR, which prevented Fe2+ oxidation and favored only partial Fe2+ autoxidation, respectively. Lipid peroxidation was inhibited by superoxide dismutase via increased formation of H2O2 from O2-. and excessive Fe2+ oxidation. Lipid peroxidation was also inhibited by high concentrations of ADR, which favored maximum Fe2+ release but also caused excessive Fe2+ autoxidation via formation of very high ADR:Fe2+ molar ratios. These results highlighted multiple and diverging effects of ADR, O2-., and H2O2 on iron release, iron (auto )oxidation and lipid peroxidation. Stimulation of malondialdehyde formation by catalase suggested that lipid peroxidation was not promoted by reaction of Fe2+ with H2O2 and formation of hydroxyl radical. The requirement for both Fe2+ and Fe3+ was indicative of initiation by some type of Fe2+/Fe3+ complex. PMID- 2310193 TI - Isolation and characterization of a second lectin (SNA-II) present in elderberry (Sambucus nigra L.) bark. AB - A second lectin (SNA-II) has been isolated from elderberry (Sambucus nigra L.) bark by affinity chromatography on immobilized asialo-glycophorin. This lectin is a blood group nonspecific glycoprotein containing 7.8% carbohydrate and which is rich in asparagine/aspartic acid, glutamine/glutamic acid, glycine, valine, and leucine. Gel filtration on Superose 12 gave a single symmetrical peak corresponding to Mr, 51,000; SDS-acrylamide electrophoresis gave a single polypeptide, Mr, 30,000. Hence SNA-II appears to be a homodimer. The lectin is a Gal/GalNAc-specific lectin which is precipitated by glycoproteins containing GalNAc-terminated oligosaccharide chains (e.g., asialo-ovine submaxillary and hog gastric mucins), and by glycoproteins and polysaccharides having multiple terminal nonreducing D-galactosyl groups as occur in asialoglycophorin, asialo laminin and Type 14 pneumococcal polysaccharide. The carbohydrate binding specificity of SNA-II was studied by sugar hapten inhibition of the asialo glycophorin precipitation reaction. The lectin's binding site appears to be most complementary to Gal-NAc linked alpha to the C-2, C-3, or C-6 hydroxyl group of galactose. These disaccharide units are approximately 100 times more potent than melibiose, 60 times more potent than N-acetyllactosamine, and 30 times more potent than lactose. Interestingly, the blood group A-active trisaccharide containing an L-fucosyl group linked alpha 1-2 to galactose was 10-fold poorer as an inhibitor than the parent oligosaccharide (GalNAc alpha 1-3Gal), suggesting steric hindrance to binding by the alpha-L-fucosyl group; this explains the failure of the lectin to exhibit blood group A specificity. PMID- 2310195 TI - Identification of 8 alpha,25-dihydroxy-9,10-seco-4,6,10(19)-cholestatrien-3-one as a product of metabolism of 25-hydroxycholecalciferol by liver microsomes. AB - The ability of liver microsomes, sites of synthesis of 25-hydroxycholecalciferol, to further metabolize 25-hydroxycholecalciferol has been assessed. When liver microsomes were incubated with 25-hydroxycholecalciferol in the presence of cytosol, a metabolite was isolated that comigrated with 8 alpha,25-dihydroxy-9,10 seco-4,6,10(19)-cholestatrien-3- one in three different chromatographic systems. The ultraviolet spectrum (220-350 nm) and mass spectrum of the purified metabolite were identical to that of synthetic 8 alpha,25-dihydroxy-9,10-seco 4,6,10(19)-cholestatrien-3-one. This study indicates that liver microsomes convert 25-hydroxycholecalciferol to 8 alpha,25-dihydroxy-9,10-seco-4,6,10(19) cholestatrien-3-one. The significance of this metabolite, which has been shown previously by others to be produced by alveolar macrophages, has yet to be determined. PMID- 2310196 TI - Aldehyde dehydrogenase heterogeneity in rat hepatic cells. AB - In normal rat liver, aldehyde dehydrogenase (Aldehyde:NAD+ oxidoreductase, EC 1.2.1.3; ALDH) is found primarily in mitochondrial and microsomal fractions. During hepatocarcinogenesis, an additional tumor-associated aldehyde dehydrogenase (T-ALDH) is detectable in the cytosol of preneoplastic and neoplastic cells. We report here differences in the ALDH distribution pattern in different rat hepatoma cell lines compared to normal rat hepatocytes. Of the four basal ALDH enzymes, one mitochondrial ALDH and one microsomal ALDH account for 96% of total ALDH molecules detectable with our probes in normal hepatocytes. The other two mitochondrial and microsomal ALDH enzymes are only detectable in the appropriate subcellular fraction from large populations of cells. The tumor associated ALDH is not detectable in normal hepatocytes. In addition to varying amounts of T-ALDH in the six different rat hepatoma cell lines examined, differences in the amounts of mitochondrial and microsomal ALDHs also occur in both high and low T-ALDH activity hepatoma cell lines. Each of five ALDH enzymes examined has a characteristic half-life varying from 45 min to 95 h. PMID- 2310197 TI - Determination of tryptophan, tyrosine, and phenylalanine by second derivative spectrophotometry. AB - Second derivative spectrophotometry has been useful for the determination of aromatic amino acids. However, published methods produce erroneous results, because those methods measure second derivative values by the vertical distance between peak and trough which is subject to variation according to the aromatic amino acid composition of proteins. This paper presents a method of second derivative spectrophotometry which measures second derivative absorbance values by means of the vertical distance from baseline to the derivative curve at a wavelength specifically assigned to each aromatic amino acid, and makes corrections for the interference from other amino acids at the same wavelength. The Appendix describes a computational method for obtaining absolute values of second derivative absorbances directly from normal absorbance values without using the spectrophotometer's derivative mode, because most commercial instruments produce completely arbitrary second derivative values which make comparison of data obtained on two different instruments impossible. PMID- 2310199 TI - Interactions of triply phosphorylated human beta-casein: monomer characterization and hydrodynamic studies of self-association. AB - The triply phosphorylated form of human beta-casein comprises about 15% of that fraction and is thus a significant component about midway between the two extremes of zero and five phosphoryls. Its partial specific volume, v, of 0.74 +/ 0.01 and absorbancy, E1% 1 cm, 280 nm, of 6.2 +/- 0.2 are almost identical to the other human beta-caseins. Equilibrium dialysis gave an average of 3.1 +/- 0.4 major Ca2+ binding sites at 37 degrees C with Kdiss = 8.6 x 10(-4) M. Sedimentation and viscosity at low temperatures or in 3.3 M urea suggested a prolate ellipsoidal monomer with 1.4 g H2O/g protein, 10 nm in length and 1.4 nm in width. The concentrated charge of the phosphoryls may be near one end of the ellipsoid, allowing the molecules to align with the flow in the viscometer at low concentration but, due to intermolecular electrostatic interactions, not when concentration is high. This would provide a reason for the heretofore unexplained curvature in the plots of reduced viscosity, eta red, vs beta-casein protein concentration. Self-association increased with temperature. At 37 degrees C in low salt buffer, s20,W was 16 S, which increased to about 33 S as ionic strength, I, was increased to 0.2 and above. At the same time, eta red in low salt buffer decreased from about 22 ml/g at 4 degrees C to a constant value of about 5 ml/g above 23 degrees C. A similar value for eta red at 37 degrees C, which was almost independent of protein concentration, was obtained at I greater than 0.25, giving an extrapolated intrinsic viscosity value of [eta] = 4.0 ml/g. Using this value and assuming a spherical aggregate, calculations suggest a radius of 9 nm with about 48 monomers and 0.86 g H2O/g protein. PMID- 2310198 TI - Presence of the cytosolic factor stimulating the import of precursor of mitochondrial proteins in rabbit reticulocytes and rat liver cells. AB - Previously we purified a cytosolic factor that stimulates the import of the extrapeptide (the synthetic peptide of the presequence of ornithine aminotransferase) into the mitochondrial matrix (Ono, H., and Tuboi, S., 1988, J. Biol. Chem. 263, 3188-3193). In this work this cytosolic factor was shown also to stimulate the import of the precursors of ornithine aminotransferase, a large subunit of succinate dehydrogenase, and sulfite oxidase. The amounts of these precursors bound to the outer mitochondrial membrane were increased by this cytosolic factor, suggesting that the cytosolic factor participates in the recognition step in the import process of the precursor protein. When the cytosolic factor was applied to an ATP-agarose column, the import-stimulating activity was recovered entirely in the unadsorbed fraction. Immunochemical studies showed that in these conditions the 70-kDa heat shock-related protein (Hsp 70) was present exclusively in the fraction adsorbed to the ATP-agarose column. The cytosolic factor is thus different from the 70-kDa heat shock-related protein, which was identified as a factor required for the import of mitochondrial proteins in yeast. The cytosolic factor was also detected in the cytosol of rat liver cells, and a considerable amount of this factor was recovered from rat liver mitochondria by washing them with high salt buffer, suggesting that the cytosolic factor has affinity to the outer mitochondrial membrane and binds to its receptor on the membrane. From these results, we conclude that the cytosolic factor forms a complex with the precursor of mitochondrial protein and then this complex binds to the outer mitochondrial membrane, probably via the receptor of the cytosolic factor. PMID- 2310200 TI - Effects of vitamin E on prostacyclin release and lipid composition of the ischemic rat heart. AB - Free radical-mediated reperfusion injury has been established as an important mechanism leading to post-ischemic reperfusion myocardial damage. The present study was undertaken to determine the protective role of vitamin E, a membrane bound free-radical scavenger, on ischemia-reperfusion myocardial injury. After 4 months of feeding a semipurified diet containing 0, 30, and 3000 ppm of R,R,R, alpha-tocopherol acetate, rat hearts were subjected to Langendorff perfusion. Myocardial damage was judged by the release of creatine phosphokinase (CPK) after 45 min of global ischemia followed by 20 min of reperfusion. Effluent CPK was significantly lowered in the two tocopherol-supplemented groups, although increasing dietary vitamin E by 100-fold above requirement did not confer further protection. However, effluent prostacyclin, detected as the stable metabolite 6 keto-PGF1 alpha by radioimmunoassay, was potentiated by dietary vitamin E in a dose-dependent manner. Analysis of lipids in cardiac subcellular fractions showed considerable enrichment of tocopherol in these membranes by diets, but the levels of polyunsaturated fatty acids, phospholipids, and cholesterol were essentially unchanged by dietary treatment or ischemia-reperfusion. These data demonstrated that requirement level of tocopherol (30 ppm) in the diet is sufficient to protect against reperfusion injury of the myocardium and suggests that tocopherol is important in maintaining cardiac prostacyclin synthesis under conditions of oxygen stress. PMID- 2310201 TI - [Anti-tumor marine natural products]. AB - In anticipation of developing new anti-cancer drugs from marine organisms of rich species, a variety of anti-tumor substances having diverse chemical structures have been discovered. Among those marine anti-tumor substances, which were reviewed in a previous paper [Jpn. J. Cancer Chemother., 16, 1-8 (1989)], several compounds promising as anti-cancer drugs are detailed in this article. They are didemnin B from marine tunicate, bryostatin 1 from marine bryozoa, and dolastatin 10 from sea hare. In addition, several anti-tumor marine sponge constituents: halichondrin B, calyculin A, and mycalamides A and B, are briefly reviewed. PMID- 2310202 TI - [Phase I clinical study of MX2 (KRN 8602)]. AB - KRN 8602 is a new antineoplastic drug with the chemical structure, 3'-deamino-3' morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. This drug was developed in an attempt to improve the clinical efficacy of currently used anthracyclines. In preclinical studies, KRN 8602 has been shown to produce less cardiotoxicity and alopecia, yet has comparable antitumor effects to adriamycin. In addition, KRN 8602 has shown antitumor effects on adriamycin-resistant tumors. A phase I clinical study was undertaken to determine the toxicity of KRN 8602 given as a single i.v. dose. Toxicity evaluation included CBC with differentials, platelet counts, SMA chemistry profile, EKG, urinalysis, plain chest X-ray and physical examination. Myelosuppression was the major side effect noted with leukopenia, and especially neutropenia, being dose-limiting. The degree of WBC suppression was dose-related and MTD appears to be 30 mg/m2. Nausea and vomiting were observed in cases who had received more than 10 mg/m2. No patient had alopecia. No obvious cardiotoxicity in this study. Maximum total cumulative dose of KRN 8602 was 450 mg/m2. Further observation is necessary to confirm this point. In this study of 10 cases, one breast carcinoma with bilateral lung metastasis revealed definite regression of metastasis for more than 18 months with this agent alone. This patient had previous chemo- and hormone therapy, containing adriamycin. The above preliminary phase I clinical study suggests strongly the usefulness of KRN 8602, and further investigations are indicated. PMID- 2310203 TI - [Organ distribution of CDDP following intra-vaginal administration]. PMID- 2310204 TI - My organ is bigger than your organ. PMID- 2310205 TI - Multiple keratoacanthomas and junctional epidermolysis bullosa. A therapeutic conundrum. PMID- 2310206 TI - Chronic actinic dermatitis. Study of the spectrum of chronic photosensitivity in 12 patients. AB - Twelve patients with photodermatitis for longer than 3 months' duration were identified: 1 patient with chronic photocontact dermatitis, 1 with persistent photosensitivity following exposure to a systemic medication, 6 with persistent light reactivity, and 4 with actinic reticuloid. There were 10 men and 2 women, ranging in age from 27 to 81 years, with a mean age of 62 years. The duration of the eruption ranged from 6 months to 20 years. Persistence of photosensitivity to quinidine, which is analogous to persistent light reactivity, was documented in 1 patient, and evolution from photocontact dermatitis to actinic reticuloid was observed in 2 others. These data, along with those reported in the literature, indicate that chronic photocontact dermatitis, persistent photosensitivity to systemic agents, persistent light reactivity, photosensitive eczema, and actinic reticuloid should be considered as entities occurring along a continuum, and the term "chronic actinic dermatitis" is suggested to refer to these entities. Eight (67%) of the 12 patients had skin type VI and 2 others (17%) had skin type V, percentages markedly higher than those of the general patient population, demonstrating that chronic actinic dermatitis is not uncommon among individuals with dark skin. PMID- 2310207 TI - Elevated plasma histamine levels in systemic sclerosis (scleroderma). AB - Systemic sclerosis is characterized by excessive deposition of collagen and other matrix proteins in the skin and internal organs. One hypothesis supports fibroblast stimulation for production of excess amounts of collagen by factors present in the blood or released by cells composing inflammatory tissue infiltrates. Increased numbers of mast cells are present in the involved skin of patients with systemic sclerosis, and histamine has been thought to be a possible mediator of fibrosis in this and other fibrotic conditions. We therefore measured plasma histamine levels in 32 patients with systemic sclerosis and found elevated levels in 18 patients (56%). Elevated plasma histamine levels were more common in patients with diffuse disease (74%), in contrast to limited disease (31%). The degree of clinical activity and the duration of disease could not be correlated with histamine levels. PMID- 2310208 TI - Photochemotherapy of generalized granuloma annulare. AB - Various forms of treatment for generalized granuloma annulare have been employed with little success. The results of treatment with topical and intralesional corticosteroids, as well as systemic therapy with corticosteroids, salicylates, aspirin, niacinamide, and chloroquine, have been generally disappointing. We describe five patients with generalized granuloma annulare of several years' duration who were treated with oral psoralen plus ultraviolet A irradiation. Lesions were present on the extremities, buttocks, and trunk in the form of macules, papules, and plaques. One patient also had perforating lesions on her thighs. Flattening of the lesions with decreased erythema and pigmentation was noted as early as 1 month after initiation of treatment. Complete clearance was achieved in all patients. Maintenance therapy has been required, resulting in prolonged disease-free intervals. Although the mechanism of action of oral psoralen plus ultraviolet A irradiation in granuloma annulare is unclear, one possibility is selective elimination of the cells that are responsible for initiating the disease. PMID- 2310209 TI - Chronic actinic dermatitis. A unifying concept. PMID- 2310210 TI - Follicular purpuric macules of the extremities. Scurvy. PMID- 2310211 TI - Rectangular reticulate patches on the pretibial areas. Erythema ab igne. PMID- 2310212 TI - Leg dermatitis. Dermatitis at vein graft site. PMID- 2310213 TI - Factitial leg ulcers associated with an unusual sleep disorder. PMID- 2310214 TI - Psoriatic alopecia. PMID- 2310215 TI - Cyclosporine therapy for bullous erythema multiforme. PMID- 2310216 TI - Single dose of albendazole in the treatment of cutaneous larva migrans. PMID- 2310217 TI - Fixed cutaneous sporotrichosis. PMID- 2310218 TI - Bilateral breast tumours in acute lymphatic leukemia. AB - We report on a patient with acute lymphatic leukemia, who developed bilateral mammary deposits. PMID- 2310219 TI - Verrucous carcinoma of the cervix. AB - Verrucous carcinoma of the cervix is a very rare variant of squamous cell carcinoma at this site. We report such a case in an 80-year-old woman because it presented difficulties with diagnosis and was successfully treated by vaginal hysterectomy. PMID- 2310220 TI - Is poor pregnancy outcome a risk factor in rheumatoid arthritis? AB - Previous work has suggested that prior poor reproductive outcome may be a risk factor in rheumatoid arthritis (RA). A case-control study of 195 women with RA and 462 control women from two different sources is presented here. No increase in rates of spontaneous abortion was seen in the women with RA; indeed a protective effect was seen with an age adjusted odds ratio of 0.6 (95% confidence interval (CI) 0.4 to 0.9). A non-significant increase in stillbirth rates was seen in women with RA, producing an age adjusted odds ratio of 1.5 (95% CI 0.7 to 3.4). No differences in rates of induced abortion were seen. Thus although hormonal and gynaecological factors are undoubtedly important in the aetiology of RA, it was not possible to confirm that prior poor reproductive outcome is a risk factor in RA. PMID- 2310221 TI - Immunogenetic heterogeneity of seronegative rheumatoid arthritis and the antiperinuclear factor. AB - HLA typing was carried out in 132 patients with rheumatoid arthritis (RA) with long term follow up, and special attention was focused on rheumatoid factor negative patients. The patients were divided into four groups: 55 patients with a seropositive RA and a positive antiperinuclear factor (group A); 39 seropositive patients but a negative antiperinuclear factor (group B); 14 patients consistently seronegative for 3-28 years (mean 11.8 years) but positive for antiperinuclear factor (group C); patients consistently negative for 3-28 years (mean 11.8) and also negative for antiperinuclear factor (group D). The prevalence of HLA-DR4 was 31/55 (56%), 29/39 (74%), 10/14 (71%), and 9/24 (37%) for groups A, B, C, and D respectively, and in all groups was significantly higher than in 277 healthy controls (55/277, 20%). No significant difference was found between seropositive (groups A and B) and seronegative (groups C and D) patients, but groups A, B, and C had higher prevalences than group D. It is concluded that in seronegative RA HLA-DR4 is preferentially associated with the antiperinuclear factor positive group. PMID- 2310222 TI - Measurement of plasma concentrations of polymorphonuclear elastase-alpha 1 proteinase inhibitor (elastase-alpha 1 antitrypsin) in patients with rheumatoid arthritis: interference by rheumatoid factor. AB - The plasma concentration of granulocyte elastase in complex with alpha 1 proteinase inhibitor was determined in 32 patients with rheumatoid arthritis and eight with seronegative spondarthritis complicated by peripheral joint synovitis. Most patients had concentrations of complex which were within the range of the control group when measured by an 'in-house' enzyme linked immunosorbent assay, though several of the patients with rheumatoid arthritis had raised concentrations. When the complexes were measured by a commercially available assay, however, much higher values were obtained for many of the patients with rheumatoid arthritis. Evidence is presented indicating that the commercially available assay may suffer seriously from interference by rheumatoid factor. The possibility is discussed that most patients with rheumatoid arthritis may have plasma concentrations of elastase-alpha 1 PI which are normal or only slightly raised, and that previously published reports using assay systems similar to that available commercially might also have produced falsely raised values for many individuals with rheumatoid arthritis. PMID- 2310223 TI - Hypercalcaemia in rheumatoid arthritis revisited. AB - The prevalence and mechanisms of hypercalcaemia were studied in a series of patients attending a regional referral centre for rheumatic diseases. In a prospective study one case of hypercalcaemia due to primary hyperparathyroidism was found in 251 consecutive patients who were screened over a three month period. In a retrospective study of 39 patients who had been discovered to be hypercalcaemic during the preceding 12 months known cases of hypercalcaemia were found in 38 (97%) cases. Primary hyperparathyroidism was the most common cause (n = 24; 62%), followed by thiazide treatment in five (13%), cancer in three (8%), immobility in three (8%), vitamin D toxicity in two (5%), and chronic liver disease in one (3%). In one case the diagnosis remained unclear after full investigation. This study shows that the causes of hypercalcaemia in rheumatological patients are similar to those in the general population. These observations contrast with previous reports, which suggested that hypercalcaemia may be a complication of rheumatoid arthritis itself. PMID- 2310224 TI - Cheiroarthropathy and long term diabetic complications in Nigerians. AB - Two hundred and fifty six consecutively ambulant diabetic patients attending a Nigerian diabetic clinic for the presence of cheiroarthropathy were examined using standard criteria. Forty eight (19%) had limited joint mobility of the hand, a prevalence higher than the 4% (2/56) observed in a non-diabetic population matched for age and sex. Limited joint mobility was twice as prevalent in the insulin treated (16/50, 32%) than in the non-insulin dependent (32/206, 16%) diabetics. Indices such as age, duration of diabetes, and glycaemic control (as assessed by integrated blood glucose concentration over the previous 12 months and glycated haemoglobin (HbA1c concentrations) were the same in the diabetics with and without limited joint mobility. The prevalence of cataracts (18/48, 38%) and background retinopathy (8/48, 17%) was higher in diabetics with limited joint mobility than in those without (respectively 6-9% and 5-6%); hypertension, peripheral neuropathy, and foot ulcers, however, were about equally common in the two groups of diabetics (with and without limited joint mobility). Nephropathy appeared commoner in diabetic subjects without limited joint mobility. Our results confirm previous observations in Caucasians of an increased prevalence of limited joint mobility in diabetes, especially those receiving insulin treatment, and also showed that limited joint mobility could predict the presence of retinopathy and cataracts in those diabetics. Neuropathy and hypertension were not commoner in our diabetics with limited joint mobility (unlike in the Caucasian population), suggesting that racial factors may underlie the predictive value of limited joint mobility in diabetic microangiopathy. PMID- 2310225 TI - Microfibrillar meshwork of the synovial lining and associated broad banded collagen: a clue to identity. AB - The surface layer of synovial interstitium lining the rabbit knee was studied by transmission electron microscopy. Over a distance of 2-3 microns normal to the surface the interstitium contained a network of fine microfibrils (diameter 9.3 (0.7) nm, mean (SEM] which was quite dense in places (fractional area of projection 0.189 (0.023], and stained with ruthenium red. Periodic collagen fibrils were relatively scanty and fine (diameter 32 (2) nm) in this surface layer. Broad cross-striated bundles occurred in association with the microfibrils and B cells. These fibrous long spacing bundles (FLS) had a single period of 92.8 (2.8) nm with a broad dark band (37.6) (1.8) nm--so called 'zebra collagen'. Both the periodicity of the FLS and the morphological characteristics of the microfibrils are typical of type VI collagen, a widespread constituent of soft connective tissues. The functional importance of the inner microfibril network is likely to be mechanical, biochemical (glycosaminoglycan and glycoprotein entrapment), and to a very minor degree hydraulic resistance. PMID- 2310226 TI - Comparison of labial and sublingual salivary gland biopsies in the diagnosis of Sjogren's syndrome. AB - This study was designed to compare labial and sublingual salivary gland biopsies in the diagnosis of Sjogren's syndrome (SS). Fourteen labial and 29 sublingual specimens were considered positive. There was a better correlation between infiltration of the ductal structure and the focus score in the sublingual salivary gland biopsy than in the labial salivary gland biopsy. Use of sublingual salivary gland biopsy as an additional diagnostic tool in SS is therefore suggested. PMID- 2310227 TI - A novel assay for neutrophil clustering activity of human sera: relation to disease activity and neutropenia in systemic lupus erythematosus. AB - A simple and reproducible method for the measurement of serum neutrophil clustering activity was developed. High clustering activity was found in 19/30 patients with active systemic lupus erythematosus (SLE), and 14/20 of those with severe disease flares. In contrast, 0/10 patients with quiescent SLE and 2/20 patients with rheumatoid arthritis had high neutrophil clustering activity. Particularly high clustering activity was found in patients with SLE with lupus glomerulonephritis and in certain patients with central nervous system disease. An inverse correlation was found between neutrophil clustering activity and peripheral blood neutrophil count in patients with SLE not treated with glucocorticoids, and clustering activity was high in all patients with low neutrophil counts in this group. A moderate correlation was found between neutrophil clustering activity and C1q binding circulating immune complexes. Non steroidal anti-inflammatory drugs and glucocorticoids had little direct effect on neutrophil clustering activity. PMID- 2310228 TI - Successful pregnancy in a woman with systemic sclerosis while taking nifedipine. AB - The case is reported of successful conception and pregnancy in a woman with systemic sclerosis while receiving continuous treatment with nifedipine 30 mg/day, after a previously poor obstetric record and involuntary secondary infertility. PMID- 2310229 TI - Reiter's cramp. AB - We report the occurrence of writer's cramp in a 31 year old B27 positive man with a recent past history of Reiter's syndrome. Although aware of the close linguistic relation between the pen and the penis, we have not previously encountered the two diseases in a single patient. PMID- 2310230 TI - Listeria monocytogenes infection in a prosthetic knee joint in rheumatoid arthritis. AB - The prosthetic knee joint of a 64 year old woman with severe rheumatoid arthritis was found to be infected with Listeria monocytogenes. After treatment with intravenous antibiotics, symptoms gradually resolved. She subsequently received prolonged treatment with oral co-trimoxazole and 18 months later remained well. PMID- 2310231 TI - Polymyositis and cyclosporin A. PMID- 2310232 TI - Toxic shock syndrome associated arthropathy. PMID- 2310233 TI - Destructive arthropathy after successful renal transplantation. PMID- 2310234 TI - Lack of serum antibodies to native type II collagen in leprosy. PMID- 2310235 TI - Magnetic resonance imaging of the shoulder in patients with rheumatoid arthritis. AB - To evaluate the ability of magnetic resonance imaging (MRI) to detect shoulder abnormalities 18 patients (36 shoulders) with rheumatoid arthritis (RA) and shoulder complaints were studied. Osseous abnormalities of the glenoid and humeral head were readily detected with MRI. The imaging planes used were not suitable for the evaluation of acromioclavicular joint involvement. Magnetic resonance imaging depicted soft tissue abnormalities that were not clearly visualised by plain film radiography, such as involvement of rotator cuff tendons and subacromial bursae, joint effusion, and muscular atrophy. Magnetic resonance imaging appears to be a sensitive method for evaluation of glenohumeral joint changes in patients with RA. PMID- 2310236 TI - 100 consecutive common duct explorations without mortality. AB - It has been suggested that the incidence of morbidity and mortality after common duct exploration no longer justifies its use in patients with a gallbladder in situ. Therefore endoscopic sphincterotomy has been advocated for removal of common duct stones before cholecystectomy in selected patients. The purpose of this study was to determine our current rate of retained common duct stones and the morbidity and mortality rates associated with common duct exploration. Charts of 100 consecutive patients who underwent cholecystectomy and common duct exploration from January 1982 through December 1986 were reviewed. Indications for duct exploration included jaundice, dilated common bile duct, gallstone pancreatitis, multiple small stones, and abnormal intraoperative cholangiogram. Common duct exploration was done by manual technique or choledochoscopy, as determined by the surgeon's preference. Only two patients required duodenotomy for extraction of difficult stones. There were no deaths in this series of consecutive common duct exploration. The total morbidity rate was 15.7%, which included a 5.3% incidence of retained common duct stones. There was a 7.4% major complication rate, including deep vein thrombosis, bleeding gastric ulcer, and pneumonia. The remaining complications were minor and did not prolong hospitalization. There was one wound infection and no postoperative pancreatitis. None of the complications were directly attributable to choledochotomy or duct exploration. All retained common duct stones were removed by endoscopic retrograde cholangiopancreatography or by angiographic basket and did not require reoperation. It is concluded that operative common duct exploration not requiring duodenotomy is safe and does not appreciably increase the incidence of complications after cholecystectomy. Endoscopic sphincterotomy continues to be the preferable alternative to operative common duct exploration for patients with retained common duct stones. PMID- 2310237 TI - Supplemental vitamin A prevents the tumor-induced defect in wound healing. AB - To test our hypothesis that supplemental vitamin A would mitigate the impaired healing that occurs in tumor-bearing animals, six groups of C3H mice, eight per group, eating a standard commercial mouse chow ad libitum that supports normal growth, reproduction, and longevity were innoculated with 200,000 C3HBA cells. When tumors measured approximately 6 mm in diameter, the mice were anesthesized and wounded (dorsal skin incisions and subcutaneous polyvinyl alcohol sponges). Twenty-four hours later, two groups (one continued on the chow and the other started on the chow supplemented with 150,000 IU vitamin A/kg chow) underwent local tumor irradiation; two groups, one ingesting the chow, the other the vitamin A supplemented chow, were started on cyclophosphamide therapy; two groups, one ingesting the chow, the other the vitamin A supplemented chow, received neither local tumor irradiation nor cyclophosphamide therapy. An additional two groups ingesting the chow, one group neither innoculated with tumor nor wounded, the other wounded by not innoculated, served as controls. Wound breaking strength and sponge reparative collagen accumulation (assessed by hydroxyproline proline measurement) were used as indicators of wound healing. The mice were killed 12 days after wounding. Tumor presence decreased wound breaking strength and sponge hydroxyproline content; these effects were largely negated by supplemental vitamin A. Local tumor irradiation diminished the adverse effect of tumor on sponge reparative collagen content but to a lesser extent than the supplemental vitamin A. Supplemental vitamin A added to the irradiation effect on healing but irradiation did not add to the vitamin A effect. Cyclophosphamide, a systemic radiomimetic anti-tumor agent, did not alter the impaired wound healing of the tumor-bearing mice. Supplemental vitamin A mitigated the impaired wound healing in the cyclophosphamide-treated tumor-bearing mice. Supplemental vitamin A also moderated the effects of wounding, tumor, and tumor therapies (local irradiation and cyclophosphamide) on the increase in adrenal size, leukopenia, thrombocytopenia, and thymic involution (except the last was not moderated in the cyclophosphamide-treated tumor-bearing rats). The splenic enlargement in the untreated tumor-bearing wounded rats and in those treated with cyclophosphamide was lessened by supplemental vitamin A. We hypothesize that these anti-stress effects of vitamin A underlie, in part, its action in mitigating the impaired wound healing of tumor-bearing mice, including those treated by local irradiation or cyclophosphamide. These findings have implications for the care of patients with malignant tumors. PMID- 2310238 TI - Exogenous transforming growth factor-beta 2 enhances connective tissue formation and wound strength in guinea pig dermal wounds healing by secondary intent. AB - The presence of transforming growth factor-beta (TGF-beta) at the site of acute injury, its ability to attract inflammatory and connective tissue cells, and its stimulatory effect on the deposition of connective tissue matrix combine to suggest that it may play a key role in the response to injury. The effect of exogenous TGF-beta form 2 on dermal wounds healing by secondary intent was investigated using a sponge composed of collagen and heparin as a delivery vehicle. Longitudinal lenticular-shaped wounds on the dorsum of adult guinea pigs were treated at the time of wounding with delivery vehicle containing 0.5, 1, or 5 micrograms of purified, bovine bone-derived TGF-beta 2, and were compared with wounds that received vehicle only or were untreated. At days 8 and 14 the amount of connective tissue in the wounds and the extent of epithelialization were determined by histomorphometric methods, and wound breaking strength was determined. At day 8, but not at day 14, wounds treated with 1 or 5 micrograms of TGF-beta 2 contained a significantly higher proportion of connective tissue than did wounds treated with vehicle only, and they also exhibited higher wound strength. No effect on wound size or re-epithelialization was detected. The observations provide evidence that a single treatment with exogenous TGF-beta 2 delivered in collagen/heparin sponge vehicle can accelerate repair in guinea pig dermal wounds allowed to heal by secondary intent. PMID- 2310239 TI - Esophagocoloplasty in the management of postcorrosive strictures of the esophagus. AB - The clinical data, technical considerations, early and late post-operative complications, and long-term follow-up results of esophagocoloplasty in the management of 176 patients with postcorrosive stricture of the esophagus are presented. All 176 colon segments were placed in the isoperistaltic position. Left colon transplants were used in 66.47% and the right colon with terminal ileum was used in 33.52% of patients. The postoperative mortality rate in the entire series was 5.68%. In the past 10 years the postoperative mortality rate was reduced to 1.96%. Long-term follow-up examinations were done for 144 patients (81.81%). Excellent results were noted in 87.50%, satisfactory results in 10.41%, and poor results in 2.08% of surgically treated patients at regular yearly check ups during a follow-up period ranging from 1 to 24 years after operation. PMID- 2310240 TI - Chronic respiratory symptoms and occult gastroesophageal reflux. A prospective clinical study and results of surgical therapy. AB - Seventy-seven patients with a primary complaint of persistent cough, wheezing, and/or recurrent pneumonia were evaluated for the presence of occult gastroesophageal reflux disease. Fifty-four patients (70%) had increased esophageal acid exposure on 24-hour pH monitoring of the distal esophagus. In 28% of these patients the respiratory symptoms were thought to be due to aspiration because they occurred during or within 3 minutes after a reflux episode. In the other patients, the respiratory symptoms were either induced by or were unrelated to reflux episodes. The number of respiratory symptoms reported by the patients with increased esophageal acid exposure was directly related to the presence of a nonspecific esophageal motility abnormality (p less than 0.05). This suggested that a motility disorder contributes to aspiration by promoting the aboral flow of refluxed gastric juice. Seventeen patients with increased esophageal acid exposure had an antireflux operation to relieve their respiratory complaints. Patients whose respiratory symptoms induced reflux episodes were not helped by the procedure. Of the other patients, symptoms were abolished by the procedure only in those with normal esophageal motility. It is concluded that the majority of patients suffering from chronic unexplained respiratory symptoms have occult gastroesophageal reflux disease, but only a minority of them are helped by surgery. Carefully performed esophageal function studies are needed to select those patients who will benefit from a surgical antireflux procedure. PMID- 2310241 TI - Perioperative multimodality management of esophageal cancer: therapeutic or investigational? PMID- 2310242 TI - Changing cardiothoracic practice patterns. PMID- 2310243 TI - Implantable rate-responsive counterpulsation assist system. AB - To apply the potential energy source available from skeletal muscle in cardiac assistance, we developed an implantable counterpulsation assist system. This study reports the results using this implantable counterpulsation assist system in an acute in vivo animal model. Twelve dogs had a dual-chambered, extraaortic counter-pulsation pump anastomosed in parallel to the thoracic aorta. The left latissimus dorsi muscle was used to power the pump. A newly developed implantable stimulator was used to make the muscle contract in synchrony with the diastolic phase. The unique feature of this stimulator is its ability to adjust timing of muscle contraction according to changing heart rates. The stimulator is also able to detect arrhythmias, and as a safety measure, shuts down until a normal rhythm is resumed. During counterpulsation assist with the implantable counterpulsation assist system, diastolic pressure increased an average of 34 mm Hg from baseline, equivalent to a 69% augmentation. Systolic peak pressure decreased an average of 10 mm Hg, equivalent to an 11% unloading. With induced heart rate changes, the implantable counterpulsation assist system readjusted its timing, maintaining optimal counterpulsation without systolic interference. Induced ventricular tachycardia resulted in immediate shutdown of the stimulator until resumption of a normal rhythm. The feasibility of using an intraaortic balloon pump console as back-up was also demonstrated. Excellent counterpulsation was obtained with either muscle power or balloon pump console. We conclude that the implantable counterpulsation assist system can provide effective counterpulsation assist and has the potential for continuous cardiac support. PMID- 2310244 TI - Survival after surgical resection for high-grade chest wall sarcomas. AB - Indications for chest wall resection of metastatic or locally recurrent sarcoma and for subsequent bony reconstruction are controversial. Twenty-eight patients had chest wall resection for high-grade primary, metastatic, or recurrent sarcoma. In all patients, resection with selective reconstruction of the bony thorax was performed without operative mortality. Since 1980, only patients with four or more ribs resected have had selective bony reconstruction. Follow-up ranged from 8 to 132 months (median follow-up, 42 months). All deaths were related to sarcoma recurrence. The overall actuarial survival rate was 85% at 1 year, 65% at 3 years, and 59% at more than 5 years. The overall actuarial proportion without disease recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years. There was no significant difference in overall or disease free survival for patients with primary, metastatic, or recurrent tumors. The most important prognostic factors were positive margins and concomitant pulmonary resection for synchronous lung metastases. These data support aggressive resection to obtain pathologically tumor-free margins for chest wall sarcomas, whether primary, metastatic or recurrent. Reconstruction can be individualized based on the extent of resection. PMID- 2310245 TI - Ten-year experience with the porcine bioprosthetic valve: interrelationship of valve survival and patient survival in 1,050 valve replacements. AB - The porcine bioprosthetic valve was used in 440 patients having isolated mitral valve replacement (MVR), 522 patients having isolated aortic valve replacement (AVR), and 88 patients having MVR + AVR between 1974 and 1981. Patients with associated surgical procedures were excluded. Mean follow-up was 8.3 years. At 10 years, there was no difference in patient survival between those having AVR and those having MVR. Reoperations were performed on 192 patients. Endocarditis was the reason for reoperation in 3.7% of patients who had MVR and 10.6% of those who had AVR. Structural valve degeneration was the reason for reoperation in 89.7% of MVR patients and 78.8% of AVR patients (p = 0.04). Hospital mortality among patients having valve reoperations was 4.7%. At 10 years, the freedom from valve reoperation for all causes and from structural valve degeneration was significantly better for the AVR group than the MVR group (74% +/- 3% versus 61% +/- 4%, p = 0.004; and 79% +/- 3% versus 63% +/- 4%, p = 0.0006, respectively). For patients in their 60s, the 10-year freedom from reoperation was 92% +/- 2% for AVR and 80% +/- 6% for MVR (p = not significant). At 10 years, freedom from cardiac-related death and valve reoperation was best for both MVR and AVR patients in their 60s. Patients 70 years old or older rarely had reoperation but died before valve failure occurred. The 10-year freedom from all major valve related events (cardiac-related death, reoperation, thromboembolism, endocarditis, and anticoagulant-related bleeding) was practically the same for both MVR and AVR patients (48% +/- 3% versus 49% +/- 3%, respectively). The porcine bioprosthetic valve is the valve of choice only for patients 60 years old or older. Patients in their 70s have an extremely low rate of reoperation but a high rate of cardiac-related death and do not outlive the prostheses. PMID- 2310246 TI - Hospital death on a cardiac surgical service: negative influence of changing practice patterns. AB - From January 1982 through December 1985, 3,772 patients underwent a cardiac surgical procedure for coronary or acquired heart disease. Operative mortality increased from 4% in 1982 to 7% in 1985 (p less than 0.001 by chi 2 analysis). There was an increase over time of patients older than 70 years (p less than 0.001). Female patients increased from 31% in 1982 to 35% in 1985 (p less than 0.001). The percentage of patients having isolated coronary artery bypass grafting decreased from 69% in 1983 to 60% in 1985 (p less than 0.001), and hospital mortality after this procedure increased (p = 0.058). Patients requiring more complex procedures including multiple-valve operations or combined valve replacement or repair plus bypass grafting increased from 1982 through 1985 (p = 0.005). Reoperations for multiple-valve procedures or combined valve repair or replacement plus coronary artery bypass grafting also increased (p = 0.02), particularly for patients more than 70 years of age (p less than 0.001). Changing practice patterns have had a negative impact on surgical results. This evolution in cardiac surgical practice has important implications related to peer review and quality-assurance screening, diagnosis-related group reimbursement, and reporting of surgical outcomes to governmental agencies. PMID- 2310247 TI - Clinical trial of nicardipine cardioplegia in pediatric cardiac surgery. AB - To clarify the effectiveness of nicardipine, one of the dihydropyridine calcium channel blockers, for myocardial protection during cold potassium cardioplegic arrest in pediatric cardiac surgery, a clinical trial of nicardipine (0.25 mg/L) added to potassium cardioplegic solution was performed in children undergoing surgical repair of congenital heart diseases. Twenty patients were selected to receive nicardipine cardioplegia and 13 patients received a standard potassium cardioplegia, serving as a control group. Nicardipine cardioplegia provided better cardiac performance in the early postoperative period and reduced release of the MB isozyme of creatine kinase, as determined during a 48-hour postoperative period. These results suggest that nicardipine added to cold potassium cardioplegic solution offers additional protection for the myocardium during ischemia and postischemic reperfusion in pediatric cardiac surgery. PMID- 2310248 TI - Reduction of myocardial injury with verapamil before aortic cross-clamping. AB - The effect of verapamil administered before aortic cross-clamping was assessed in 40 patients undergoing elective coronary artery bypass grafting. Myocardial protection consisted of cold blood potassium cardioplegia, topical ice slush, and moderate (28 degrees C) systemic hypothermia. Patients were randomly divided into two groups: group 1 (18 patients) received verapamil (0.1 mg/kg up to 10 mg) intravenously three to five minutes before aortic cross-clamping; group 2 (22 patients) did not (control). Myocardial injury was assessed by cumulative release of the cardiac-specific isoenzyme of creatine kinase (CK-MB) after release of the aortic cross-clamp. Release of CK-MB was significantly lower in the verapamil group (44.9 +/- 6.2 versus 72.2 +/- 9.0 IU at 24.5 hours, p = 0.005). Calculated total infarct size was also lower in the verapamil group (6.0 +/- 0.9 versus 8.9 +/- 1.0 g-Eq, p = 0.035). Individual CK-MB release curves showed either one or two peaks. The two-peak pattern was more frequent in control patients (18 of 21 control patients versus 6 of 18 verapamil patients, p = 0.001) and was associated with a larger infarct size. Atrioventricular pacing was not required in any verapamil patient, but was needed in 1 control patient. We conclude that verapamil administered before aortic cross-clamping protects against myocardial injury during coronary artery bypass grafting with no increase in the incidence of atrioventricular block. PMID- 2310249 TI - Transatrial relief of diffuse subaortic stenosis after ventricular septal defect closure. AB - Transatrial enlargement of the left ventricular outflow tract for serious obstruction was performed in 3 patients with previous ventricular septal defect closure. Two patients had recurrent subaortic stenosis as resection had already been performed at initial operation. In all patients, the obstruction was located below the ventricular septal defect patch. Patch enlargement of the left ventricular outflow tract was carried out by opening the ventricular septal defect patch through the tricuspid valve and extending the incision downward through the area of obstruction and the left ventricular body. All patients had uneventful postoperative course and effective relief of left ventricular outflow tract obstruction. We feel that the approach is simple and effective; it avoids a right ventriculotomy and provides a viable option in certain patients with left ventricular outflow tract obstruction. PMID- 2310250 TI - Cefamandole versus cefonicid prophylaxis in cardiovascular surgery: a prospective study. AB - We randomized 400 patients who were scheduled for an elective cardiovascular operation involving median sternotomy to receive cefamandole nafate or cefonicid in a prospective double-blind study. Three hundred fifty-seven patients were evaluable for prophylactic efficacy. Chest wound and donor site infections and early prosthetic valve endocarditis occurred more frequently with cefonicid (11 patients, 6.3%) than with cefamandole (4 patients, 2.2%) (p = 0.05). Three patients, all in the cefonicid group, required sternal debridement to control postoperative deep wound infections. Twenty-five miscellaneous postoperative infections (urinary tract infection, pneumonia, intravenous site infection, bacteremia, sepsis, Clostridium difficile diarrhea) occurred in 16 patients (9.19%) in the cefonicid group and four in 4 patients (2.19%) in the cefamandole group (p = 0.003). These data indicate that cefamandole is superior to cefonicid in preventing both surgical wound infections and miscellaneous nonsurgical infections after cardiovascular operations. PMID- 2310251 TI - Low activated coagulation time during cardiopulmonary bypass does not increase postoperative bleeding. AB - The activated coagulation time (ACT) is widely used to monitor adequacy of anticoagulation during cardiopulmonary bypass despite absence of data establishing an ACT below which adverse outcomes occur. For anticoagulation before cardiopulmonary bypass, we administered a single dose of heparin (300 U/kg) to 193 patients and measured ACT and heparin levels at intervals after administration. No additional heparin was administered to any patient. Clot formation in the cardiopulmonary bypass circuit and excessive postoperative chest tube drainage were considered outcomes indicating inadequate anticoagulation. Cardiopulmonary bypass averaged 59 +/- 23 minutes (range, 30 to 138 minutes). Activated coagulation time values at every sampling period were normally distributed. In 51 patients (26.4%) ACT values were less than 400 seconds, including 4 less than 300 seconds, at some sampling time after heparinization. Patients with low ACT values did not bleed more postoperatively than those with high ACT values, nor was bleeding related to heparin level. No clots were found in any perfusion circuit. We conclude that a minimum ACT value for adequacy of heparinization is not yet defined but that it is less than 400 seconds. PMID- 2310252 TI - Surgical excision of intracardiac myxomas: a 20-year follow-up. AB - Since November 1968, 54 patients have undergone excision of an intracardiac myxoma, which was located in the left atrium in 46 (85%), in the right atrium in 6 (11%), and in the right ventricle in 2 (4%). There were 35 female and 19 male patients with a mean age of 48 +/- 14 years (range, 7 to 68 years). Four patients were asymptomatic; the others were seen mostly with exertional dyspnea, palpitation, signs of systemic illness, and syncopal episodes. Before operation, embolic episodes occurred in 13 patients with a left atrial myxoma. There were two early (3.7%) and two late deaths (3.8). Actuarial survival at 20 years is 91% +/- 4%, and most of the current survivors are asymptomatic at a mean follow-up of 6.5 +/- 5 years (range, 0.2 year to 20 years). Noninvasive reevaluation was performed with echocardiographic studies in 44 patients and 24-hour electrocardiographic monitoring in 34. No instances of tumor recurrence were observed, and there was a low incidence of major supraventricular arrhythmias late postoperatively. We conclude that excision of intracardiac myxomas is curative and long-term survival is excellent. The transseptal approach provides adequate exposure and allows complete removal of the tumor regardless of its location. PMID- 2310253 TI - Bacteremia and sternal infection after coronary artery bypass grafting. AB - Sternal wound infection remains a source of substantial morbidity and mortality after coronary artery bypass grafting. We noted an association between bacteremias and sternal wound complications in these patients. A review of 835 consecutive coronary bypass patients showed a 3.2% incidence of bacteremia and a 1.9% incidence of deep and superficial sternal wound infection. The sternal wound was the most common source of bacteremia, accounting for 59% of the infections. Coagulase-negative Staphylococcus was responsible for one half of the sternal wound infections. Often, a positive blood culture was the first manifestation of wound infection, occurring before local signs were manifest. We recommend multiple blood cultures in postoperative coronary bypass patients with pronounced fever. If no source of infection can be identified, sternal wound aspirate may be revealing. Appropriate early wound management can then be carried out, maximizing chances for good recovery. PMID- 2310254 TI - Recent experience with major sternal wound complications. AB - During a recent 1-year period, 31 patients sustained a major sternal wound infection and sternal dehiscence developed in 6 patients. Multiple potential risk factors were tabulated in these patients and in a control group selected from 1,521 patients undergoing sternotomy during the same time period. The overall infection rate was 2.1%, and the mortality rate in the patients with sternal infection or dehiscence was 16.2%. Chronic obstructive pulmonary disease, prolonged intensive care unit stay, respiratory failure, connective tissue disease, and male sex were significantly higher in the group with sternal infection or dehiscence (p less than 0.05). Advanced age and low cardiac output episodes were more frequent in this group, but only approached statistical significance. Although several risk factors may have been interrelated, male sex and the presence of pulmonary disease were statistically independent predictors of sternal wound infection. Risk factors may be helpful in identifying high-risk patients for additional prophylactic measures. PMID- 2310255 TI - Surgical cure of automatic atrial tachycardia by partial left atrial isolation. AB - Partial left atrial isolation was performed in a 16-year-old girl with persistent atrial tachycardia refractory to antiarrhythmic agents for 3 years. Intraoperative atrial epicardial and endocardial mapping showed that the earliest atrial activation occurred in an area lateral to the junction of the right superior pulmonary vein and the left atrium. An incision isolating the right half of the left atrial body containing the area of the earliest atrial activation and both right pulmonary veins from the remainder of the left atrium was made. The incision was then reapproximated. An excision encircling the interatrial septum containing the upper anterior portion of the septum with early activation was also made, and the atrial septal defect was repaired with a pericardial patch. The patient has been in sinus rhythm and free of arrhythmia for a follow-up period of 12 months. PMID- 2310256 TI - Dissection of the left main coronary artery: diagnosis by angioscopy. AB - A 58-year-old woman with mitral valve disease was investigated with cardiac catheterization. At catheterization, a suspected dissection of the left main coronary artery occurred. This diagnosis was confirmed at urgent operation by intraoperative angioscopy. The patient underwent mitral valve replacement and coronary artery bypass grafting and made a good postoperative recovery. Coronary angioscopy at operation provides a useful means of diagnosing pathology in the left main coronary artery. PMID- 2310257 TI - Early manifestation of noncalcific aortic stenosis after porcine valve replacement. AB - Symptoms of noncalcific aortic stenosis developed in a 57-year-old man 3 months after implantation of a Carpentier-Edwards porcine heterograft. The glutaraldehyde-processed bioprosthesis was removed 7 months after implantation and replaced with a No. 3 Medtronic Hall valve. PMID- 2310258 TI - Cor triatriatum, coarctation of the aorta, and ventricular septal defect: a rare, surgically correctable anomaly. AB - A case of cor triatriatum associated with coarctation of the aorta and ventricular septal defect, successfully treated surgically by a staged approach, is reported. This combination is a very uncommon but potentially correctable cause of congestive heart failure and death in infancy. Early accurate diagnosis aided by an awareness of this combination and prompt surgical correction should yield excellent long-term results. PMID- 2310259 TI - Congenital aneurysm of the left atrial wall in infancy. AB - A 5-month-old male infant with congenital left atrial aneurysm is reported. The youngest patient previously reported was 2 1/2 years old. This case is unusual because the patient was an infant and because of the degree of mitral insufficiency and acute cardiac decompensation observed in the patient. PMID- 2310260 TI - Multiple free (aorta-coronary) gastroepiploic artery grafting. AB - The use of in situ gastroepiploic artery grafts has been reported recently. In the present case, the in situ gastroepiploic artery was too short to graft both the diagonal and the obtuse marginal branches of the coronary arteries in a patient with diffuse coronary artery disease. The free (aorta-coronary) gastroepiploic artery graft was anastomosed to both arteries to form a Y graft. PMID- 2310261 TI - Myocardial abscess in a patient with AIDS-related complex: pericardial patch repair. AB - A hemophiliac with acquired immunodeficiency syndrome-related complex was seen with sepsis related to a ventricular septal abscess. The abscess was debrided and the septum was patched with a single layer of autologous pericardium. The patient recovered and survived 6 months before dying of acquired immunodeficiency syndrome. At autopsy, the septal patch was well healed with no evidence of recurrent endocarditis. PMID- 2310262 TI - Coronary artery bypass in a 15-year-old girl with pseudoxanthoma elasticum. AB - A 15-year-old girl with pseudoxanthoma elasticum and associated severe coronary artery disease underwent double coronary artery bypass using left internal mammary artery and saphenous vein. Preoperatively the patient had life threatening syncope and positive treadmill test results. The postoperative course was uneventful, and the patient has been doing well for 3 years. Pseudoxanthoma elasticum is a rare disease that can cause premature coronary arterial obstructive disease in children and adolescents. PMID- 2310263 TI - Three-dimensional image reconstruction for planning of a complex cardiovascular procedure. AB - A rare left subclavian artery aneurysm associated with a congenital arch anomaly was difficult to visualize using standard radiographic techniques. Three dimensional computer imaging produced a clear depiction of this unusual anatomy and simplified the preoperative planning. PMID- 2310264 TI - The Killingbeck pediatric lung retractor. AB - A new series of lung retractors has been designed for use in patients ranging from premature infants to large children. Their unique shape, low profile, and light weight affords excellent exposure with a minimum of trauma to tissues. PMID- 2310265 TI - Total anomalous pulmonary venous connection: surgical repair with a double-patch technique. AB - A double-patch technique has been used to repair total anomalous pulmonary venous connection in 35 patients (mean age, 4.9 months; mean weight, 4.2 kg). In all patients with supracardiac or subdiaphragmatic type of total anomalous pulmonary venous connection, repair has been accomplished by enlarging the "new" left atrium. There were three early deaths (3 of 35 = 8.6%) and no late deaths in a mean follow-up of 30 months (3 to 71 months). We propose this double-patch technique as an alternative surgical option for total anomalous pulmonary venous connection. PMID- 2310266 TI - Transvenous pacing in infants and children with congenital heart disease. AB - A technique for transvenous pacemaker implantation in children with complex heart disease is described. The use of small positive-fixation leads, introducers, retained guidewires, and atrial lead loops to allow for growth all have an important role in management of this often challenging problem. PMID- 2310267 TI - Mitral valve annuloplasty. PMID- 2310268 TI - Cryoanalgesia for postthoracotomy pain. PMID- 2310269 TI - Oxygenator failure. PMID- 2310270 TI - Hypoxemia after intraluminal oxygen line obstruction during cardiopulmonary bypass. PMID- 2310271 TI - 'Cookbook' medicine. A legal perspective. PMID- 2310272 TI - The medical day hospital. A new concept in ambulatory medical education. AB - The shift of patients from inpatient to outpatient settings as a result of various well-known economic, technologic, and demographic forces presents a challenge for internal medicine residency training programs. In response, we developed a new ambulatory site for education of medical students and residents. The Ambulatory Diagnostic and Treatment Center functions as a medical day hospital serving the needs of patients requiring intensive diagnostic or therapeutic interventions on a short-term basis. The center maintains many of the educational advantages of an inpatient service including block rotations of house officers, easy access to consultants and specialized services, and daily attending rounds while providing experience in outpatient management skills. This unit represents a new concept in ambulatory education and, if adaptable to other institutions, may be a valuable component of a broad ambulatory medicine curriculum. PMID- 2310273 TI - The impact of thoracic computed tomography in clinically staged T1, N0, M0 chest lesions. AB - We assessed the impact of thoracic computed tomography (CT) in 38 patients considered for thoracotomy for solitary pulmonary lesions characterized as T1, N0, M0 by clinical and roentgenographic staging. False-positive lymph nodes were identified by CT in four patients prompting additional surgical staging procedures in two cases. Two of three patients with false-negative clinical, roentgenographic, and CT findings had successful complete resections. The CT scan did not correctly advance the stage of, or alter the plan for, these lesions in any patient. We conclude that CT is not helpful in patients considered for diagnostic and therapeutic thoracotomy for clinical and roentgenographic T1, N0, M0 lesions. PMID- 2310274 TI - Gynecomastia and cirrhosis of the liver. AB - Hepatic cirrhosis is frequently listed as a cause of gynecomastia. We found previously that in hospitalized men the prevalence of gynecomastia was correlated with body mass index and with age. The mean body mass index and the prevalence of gynecomastia in the cirrhotic subjects (nonedematous) did not differ from those in the overall population. Because more severely cirrhotic subjects with ascites, peripheral edema, or both usually are thin, we examined 18 more severely cirrhotic subjects and 18 nonobese (mean body mass index, 20.9 +/- 0.6 kg/m2), age-matched control subjects for the prevalence of palpable gynecomastia. Total testosterone, free testosterone, total estrogen, and estradiol concentrations also were measured. Fifty percent of the control subjects had gynecomastia. Breast tissue diameter was correlated with body mass index. The prevalence of gynecomastia in the cirrhotic subjects was 44%. In these subjects no significant correlation was noted between breast tissue diameter and body mass index, presumably because the body mass index was increased owing to fluid retention. The results could not be accounted for based on medications. Serum free testosterone concentrations were lower in the cirrhotic patients than in the controls (0.11 +/- 0.02 vs 0.22 +/- 0.03 nmol/L). The total estrogen-free testosterone ratio was higher in cirrhotic patients (10.3 +/- 2.5 vs 2.6 +/- 0.5), as was the estradiol-free testosterone ratio (2.2 +/- 0.7 vs 0.5 +/- 0.1). These ratios did not differ significantly in cirrhotic subjects with and without gynecomastia. Therefore, these data indicate that factors other than the estrogen testosterone ratio are playing a role in the development of gynecomastia in both cirrhotic subjects and controls or that breast tissue sensitivity to an elevated estrogen-testosterone ratio is highly varible. PMID- 2310275 TI - Reliability and validity of an objective structured clinical examination for assessing the clinical performance of residents. AB - Clinical performance of residents should be assessed as reliably and validly as possible. This study investigated the reliability and validity of an objective structured clinical examination (OSCE) for assessing clinical performance of internal medicine residents. Residents were required to take a 17-patient OSCE in their first and second year. Reliability of the OSCE was 0.40. Validity studies indicated second-year students were significantly better than third-year students for five of six OSCE skill scores; first-year students were significantly better for three scores. Resident's scores for diagnosis, plan, and total significantly increased on their second OSCE. Generally faculty overall ratings of residents' clinical performance did not correlate with OSCE scores. American Board of Internal Medicine certifying examination scores were consistently positively correlated only with diagnosis. This 17-case OSCE is a feasible method for obtaining moderately reliable, valid data not available from other sources about the clinical performance of residents. More cases should be added to increase its reliability. PMID- 2310276 TI - Population-based frequency of dyslipidemia syndromes in coronary-prone families in Utah. AB - The frequency of familial dyslipidemia syndromes was determined from blood tests in 33 objectively ascertained families with early coronary heart disease (CHD) (two or more siblings with CHD by the age of 55 years). Three fourths of persons with early CHD in these families had 90th percentile lipid abnormalities (cholesterol level at or above the 90th percentile, triglyceride level at or above the 90th percentile, and/or high-density lipoprotein cholesterol (HDL-C) level at or less than the 10th percentile). The HDL-C and triglyceride abnormalities were twice as common as low-density lipoprotein-cholesterol abnormalities. The most common syndromes found were familial combined hyperlipidemia (36% to 48% of families with CHD), familial dyslipidemic hypertension (21% to 54% of families with CHD), and isolated low levels of HDL-C (15%), with overlapping familial dyslipidemic hypertension with familial combined hyperlipidemia and low-level HDL-C. Well-defined monogenic syndromes were uncommon: familial hypercholesterolemia being 3% and familial type III hyperlipidemia, 3%. Another 15% of families with CHD had no lipid abnormalities at the 90th percentile. Physicians should learn to recognize and treat these common familial syndromes before the onset of CHD by evaluating family history and all three standard blood lipid determinations. Failure to recognize and treat them leaves affected family members at high risk of premature CHD. PMID- 2310277 TI - The search for an optimized treatment of hypoglycemia. Carbohydrates in tablets, solutin, or gel for the correction of insulin reactions. AB - Recommendations for the treatment of insulin reactions are based more on habit than data. We investigated the efficacy in correcting blood glucose levels and alleviating clinical symptoms of hypoglycemia of seven orally administered carbohydrates--glucose in solution, tablets, and gel; sucrose in solution and tablets; a hydrolized polysaccharide solution; and orange juice--each of which provided 15 g of carbohydrate. Forty-one type I diabetic patients recently treated with insulin agreed to submit to artificially induced hypoglycemia by an intravenous injection of insulin. Corrective therapy was given when patients experienced symptoms and asked for treatment. Mean blood glucose levels 10 minutes after ingestion were found to be similar whether correction was dispensed with the tablets and the solutions of glucose, those of sucrose, or the polysaccharide preparation. However, almost no increment was obtained at this time point with the gel or the fruit juice. Fifteen and 20 minutes after carbohydrate intake, blood glucose levels were higher with the tablet forms than with the solutions, although differences only became signifiant for sucrose. Glycemic responses were again consistently lower with the sucrose gel and the orange juice. Clinical symptoms were alleviated in 14.0 +/- 0.8 minutes (mean +/- SEM) with sucrose and glucose in solution or tablets. We conclude that in moderately severe hypoglycemia, ingestion of 15 g of carbohydrate in the form of glucose or sucrose tablets or as a solution provides an effective therapy; both sugars seem equivalent. Even if sucrose lumps are better recommended in terms of cost and availability, they may not be recommendable in terms of palatability. Glucose gel or orange juice cannot be recommended, at least in light of our experimental procedure and at the dosage used therein. PMID- 2310278 TI - Snoring in a Hispanic-American population. Risk factors and association with hypertension and other morbidity. AB - Snoring was investigated in a survey of respiratory disease in Hispanic-Americans of a New Mexico community. A population-based sample of 1222 adults was studied with questionnaires and measurements of height, weight, and blood pressure. The age-adjusted prevalence of regular loud snoring was 27.8% in men and 15.3% in women. Snoring prevalence increased with age and obesity in both men and women. Cigarette smoking was also associated with snoring, but chronic obstructive lung disease and alcohol consumption were not. Snorers more frequently had hypertension, ischemic heart disease, and excessive daytime sleepiness. In contrast to other studies, after adjustment for confounding factors, there was no effect of snoring on hypertension (odds ratio, 1.0; 95% confidence interval, 0.7 to 1.5), but an effect on myocardial infarction was still demonstrable (odds ratio, 1.8; 95% confidence interval, 0.9 to 3.6). The association of snoring with sleepiness suggests that respiratory disturbance of sleep related to upper airway obstruction, such as sleep apnea, occurs more frequently in snorers in this population. PMID- 2310279 TI - Hypoalbuminemia in patients with multiple myeloma. AB - Clinical data of 65 patients with myeloma were analyzed to identify factors associated with hypoalbuminemia. The serum albumin level was not affected by patient age and gender, type of myeloma, and the occurrence of Bence Jones protein, lytic bone lesions, or hypercalcemia, and it was not related to changes in body weight or in liver and renal function. The albumin level, lower in patients with proteinuria, was unrelated to severity of proteinuria. Albumin level correlated significantly with the monoclonal IgG levels, hemoglobin concentration, clinical stage of disease, and estimated body tumor burden. Further analysis indicated the disease stage or the tumor burden as the dominant factor in determining albumin level. An albumin level of 29.0 g/L or less identified unequivocally advanced disease. Practically all patients with stage III myeloma had a serum albumin level of 37.0 g/L or less. Thus, hypoalbuminemia is primarily related to the extent of myeloma proliferation and is therefore of diagnostic and prognostic importance. PMID- 2310280 TI - Rapid correction of hypokalemia using concentrated intravenous potassium chloride infusions. AB - There are conflicting recommendations regarding the use of intravenous potassium chloride infusions for acute correction of hypokalemia. We examined the effects of 495 sets of potassium chloride infusions administered to a medical intensive care unit population. The infusion sets consisted of one to eight consecutive individual infusions, each containing 20 mEq of potassium chloride in 100 mL of saline administered. The mean preinfusion potassium level was 3.2 mmol/L, and the mean postinfusion potassium level was 3.9 mmol/L. The mean increment in serum potassium level per 20-mEq infusion was 0.25 mmol/L. No temporally related life threatening arrhythmias were noted; however, there were 10 instances of mild hyperkalemia. Our data endorse the relative safety of using concentrated (200 mEq/L) potassium chloride infusions at a rate of 20 mEq/h via central or peripheral vein to correct hypokalemia in patients in the intensive care unit. PMID- 2310281 TI - Antithyroid drug-induced agranulocytosis. The usefulness of routine white blood cell count monitoring. AB - This study was aimed at establishing the importance of routine monitoring of white blood cell counts in patients with Graves' disease receiving antithyroid drug treatment. In the 12-year period from 1975 to 1987, 15,398 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. Of these, 55 (0.4%) were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 0.5 x 10(9)/L or less. In only 12 of the 55 patients was agranulocytosis detected after the occurrence of infection (symptomatic; classic agranulocytosis). The remaining 43 patients were asymptomatic when agranulocytosis was detected during routine white blood cell count monitoring. However, 14 of these 43 patients became symptomatic several days after withdrawal of antithyroid drug treatment despite antimicrobial treatment (asymptomatic to symptomatic). Twenty-nine patients who were treated appropriately had no symptom of infection throughout the course of the disease, despite the absence of or an extremely small number of granulocytes in circulation (asymptomatic). These results suggest that a "routine monitoring" of the white blood cell count could be the most effective way of predicting and detecting agranulocytosis due to antithyroid drug treatment. PMID- 2310282 TI - Acute leukemia and cytogenetic abnormalities complicating melphalan treatment of primary systemic amyloidosis. AB - We followed up 153 patients with biopsy-proven primary systemic amyloidosis to determine their risk for acute nonlymphocytic leukemia or a dysmyelopoietic syndrome. In 10 patients cytogenetic abnormalities developed consistent with alkylator-induced damage to hematopoietic cells. In this group, the total melphalan dose ranged from 476 to 2450 mg (median, 1764 mg) administered over 21 to 92 months (median, 38 months). Eight of the 10 patients died as a direct result of pancytopenia, 1 died of progressive renal amyloid, and 1 remains alive with persistent complex cytogenetic abnormalities. Four patients had acute nonlymphocytic leukemia; 5 had a dysmyelopoietic syndrome; and 1 had a nondiagnostic bone marrow examination. Although only 6.5% of the entire group had leukemia or a dysmyelopoietic syndrome, the actuarial risk in patients surviving 3.5 years was 21%. Median survival from onset of dysmyelopoietic syndrome or acute leukemia was 8.1 months. PMID- 2310283 TI - High-normal blood pressure and early diabetic nephropathy. AB - The relationship between high-normal blood pressure (BP) levels and early diabetic nephropathy is currently unknown. Blood pressure levels were checked longitudinally for a mean of 6.6 years in 230 subjects to determine their relationship to early diabetic nephropathy as monitored by microalbuminuria. High normal BP level correlated with the presence of microalbuminuria. Microalbuminuria was 2.8 times as common in subjects with high-normal BP levels compared with those subjects with BP levels below the 90th percentile for their age. The elevated microalbumin excretion was primarily associated with high normal diastolic BP levels. Our data suggest that either microalbuminuria or high normal BP levels can precede the other. In a logistics model, diastolic BP and mean HbA1 (over 6.6 years) entered the model at similar levels, followed by duration of diabetes. When the influence of mean HbA1 was removed using logistic regression, the diastolic BP level remained a significant associated factor for the presence of microalbuminuria. PMID- 2310284 TI - The effect of patient-carried reminder cards on the performance of health maintenance measures. AB - We designed a card that patients carried and showed to their physicians at scheduled appointments to remind them to perform six health maintenance procedures: influenza vaccination, pneumococcal vaccination, rectal examination and hemoccult test, Papanicolaou's smear, physician breast examination, and mammography. Prompt sheets were also attached to all charts to remind physicians to perform these same procedures. One hundred seventy-five patients received the card and the physician prompt sheets on their charts. Two hundred forty-eight patients received only physician's prompt sheet. The card group had significant increases in the performance of influenza vaccinations (47% vs 29%), rectal examination and hemoccult tests (59% vs 46%), Papanicolaou's smears, (30% vs 20%), and physician breast examinations (52% vs 29%). There was not a significant increase in the performance of pneumococcal vaccines (22% vs 24%) or mammography (18% vs 19%). We conclude that patient-carried health maintenance reminder cards are useful in increasing the physician performance of influenza vaccinations, rectal examinations and hemoccult tests, Papanicolaou's smears, and breast examinations. PMID- 2310285 TI - Evaluation of patient, physician, nurse, and family attitudes toward do not resuscitate orders. AB - We investigated attitudes toward resuscitation by interviewing 97 competent patients classified as do not resuscitate, 60 physicians, 80 family members, and 84 nurses. In addition, 58 family members of incompetent do not resuscitate patients were interviewed. Interview patients were generally elderly, female widows with a diagnosis of malignancy. The majority (66%) preferred that their medical decision making be shared with the physician and/or family. Only 38 patients (39%) could correctly define a "living will." After hearing the definition, 59 patients (61%) thought it was a good idea to ask noncritically ill patients at the time of hospital admission, if they had a living will. Fifty-six patients (58%) said they had discussed resuscitation with their physician, whereas 44 physicians (73%) said they had discussed it with the patient. Only 53 patients (55%) said that they thought their physician understood their wishes. Sixty-five patients (67%) wanted involvement in resuscitation decisions. Forty eight patients (49%) offered "quality of life" reasons for not wanting to be resuscitated. Sixty-four patients (66%) did not think discussing resuscitation was cruel and insensitive. Eighteen physicians (30%) said they were uncomfortable discussing resuscitation with patients. We recommend introducing the topic of resuscitation early in the patient-physician relationship before diminished competency occurs. PMID- 2310286 TI - The 10-year incidence of overweight and major weight gain in US adults. AB - We estimated the 10-year incidence of major weight gain (a gain in body mass index of greater than or equal to 5 kg/m2 and overweight (a body mass index of greater than or equal to 27.8 for men and greater than or equal to 27.3 for women) in US adults using data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Persons aged 25 to 74 years at baseline were reweighed a decade after their initial examination (men, 3727; women, 6135). The incidence of major weight gain was twice as high in women and was highest in persons aged 25 to 34 years (men, 3.9%; women, 8.4%). Initially overweight women aged 25 to 44 years had the highest incidence of major weight gain of any subgroup (14.2%). For person not overweight at baseline (men, 2760; women, 4295), the incidence of becoming overweight was similar in both sexes and was highest in those aged 35 to 44 years (men, 16.3%; women, 13.5%). We conclude that obesity prevention should begin among adults in their early 20s and that special emphasis is needed for young women who are already overweight. PMID- 2310287 TI - Hypokalemia and quadriparesis. PMID- 2310288 TI - Oral nifedipine in the treatment of hypertensive urgency: cerebrovascular accident following a single dose. PMID- 2310289 TI - Nosocomial (water bed) fever. PMID- 2310290 TI - Acute tubulointerstitial nephritis with uveitis. PMID- 2310291 TI - The risks of substitution of therapeutic modalities by cheaper and sometimes less effective agents. PMID- 2310292 TI - Hypernatremia following treatment of theophylline toxicity with activated charcoal and sorbitol. PMID- 2310293 TI - Management of cerebral infarction or transient ischemic attacks. PMID- 2310294 TI - Peptic ulcer disease, cytoprotection, and prostaglandins. PMID- 2310295 TI - Acute Q fever. PMID- 2310296 TI - Influence of age on antileukemic action, subacute toxicity and tissue distribution of ambazone in B6D2F1 mice. AB - The influence of age of experimental animals on the antileukemic activity, toxicity and distribution of ambazone, a new potential antineoplastic agent, was studied in 2- and 12-month-old B6D2F1 mice. The predominant effect observed was a significant reduction of the antileukemic action of this compound in old-aged mice. Together with a slight increase in several toxicity parameters this caused a marked reduction of the therapeutic index in 12-month-old mice compared to younger individuals. Furthermore, a general tendency to increased ambazone levels in liver, kidneys and thymus of old-aged mice was observed. Our data therefore provide further evidence that age has to be taken into consideration as one factor that may account for the variety of drug response frequently observed during clinical therapy with anticancer agents. PMID- 2310297 TI - [Sialic acid in the serum--an indicator for malignant growth?]. AB - Changes of the sialic acid content of patients sera reflect growth processes of benign and malignant character. Using an enzymatic test the value of sialic acid as a primary diagnostic parameter has been investigated. We found a poor diagnostic sensitivity with exception of lung and ovarian carcinomas where the sensitivity attained nearly 90%. In monitoring of patients with pre therapeutically elevated sialic acid content in serum dropping values indicate a successful therapeutic intervention. An increase of post-therapeutic values demonstrates recurrent processes but the reaction of the serum level may be delayed up to 2 weeks. The outcome of the studies supports the notion that sialic acid is a tumor marker of very limited value. PMID- 2310298 TI - [Symposium "Rational diagnosis in oncology". 17-18 November 1988, Berlin-Buch]. PMID- 2310299 TI - [The current value of angiography within the scope of complex tumor diagnosis]. AB - The development of noninvasive imaging methods with high diagnostic accuracy in the last decade has led to a new determination of the role of angiographic techniques in oncologic diagnosis. The disadvantages of angiography are discussed and the major indications in tumor diagnosis are delineated: preoperative vascular mapping, vascular involvement of the great vessels, CT and ultrasound equivocal, selective blood sampling and interventional procedures. The increasing importance of interventional radiology in oncology is emphasized. PMID- 2310300 TI - The value of lymphography in the tumour diagnostic--the comparison lymphography with computerized tomography. AB - The main indications for lymphography by oncological patients are primary or secondary lymph node tumours. CT also became very useful in these cases. In this study the results of lymphography and computed tomography were compared in 100 patients with lymph node tumours. An absolute concurrence of both methods was found in only one half of the material. In 18% lymphography was clearly positive and CT negative. In 6% CT was positive while lymphography was negative. In 25% CT yielded important extra useful information. Lymphography and CT complement each other. Both methods are about equal in terms of sensitivity and reliability. CT is the basic method to be performed invariably prior to lymphography. PMID- 2310301 TI - Organization of cancer control in Italy. PMID- 2310302 TI - A comparison of different cloned genome segments of epizootic haemorrhagic disease virus as serogroup-specific probes. AB - The eight largest double-stranded (ds) RNA genome segments of epizootic haemorrhagic disease virus (EHDV) serotype 2 (Alberta strain) have been cloned. Of these, segments 4, 5, 6, 7, and 8 are represented by clones that correspond in size to those predicted for full-length clones. The different clones were used as nucleic acid probes to study the nucleic acid homology of cognate genes of four different EHDV serotypes. The results indicated that the 4 isolates may be subdivided in two geographic groups which include Ibaraki virus as the sole member of one group and EHDV1 (New Jersey), EHDV2 (Alberta) and EHDV6 (XBM 67- isolated in South Africa) as a second. Genome segments 1, 3, 4, 6, and 8 were found to be highly conserved with more than 90% homology amongst cognate genes of three of the members of the EHDV serogroup. Of these, segments 1 and 3 showed the largest degree of homology with cognate genes of members of the BTV serogroup. Segment 6 and 8 probes of EHDV2 (Alberta) on the other hand did not hybridize with BTV dsRNA under conditions of moderate to low stringency and are recommended for use as EHDV group-specific probes. PMID- 2310303 TI - Characterization of the DNA of granulosis viruses isolated from two closely related moths, Chilo infuscatellus and C. saccariphagus indicus. AB - Digestion of the DNA from Chilo infuscatellus and C. saccariphagus indicus GVs with the restriction endonucleases EcoRI, BamHI, XhoI, and SalI, produced readily distinguishable profiles, with very few co-migrating fragments. The approximate size of the genome was calculated to be 112kbp for both GVs. The percent relative hybridization between the two DNAs was in the range 30 to 40%. PMID- 2310304 TI - A host-cell-selected variant of influenza B virus with a single nucleotide substitution in HA affecting a potential glycosylation site was attenuated in virulence for volunteers. AB - An influenza B virus was passaged in man (virus A) and then in human embryo trachea (C) and into embryonated eggs (D) or directly into eggs (B). Virus A, B, and C had the same (cell-like) haemagglutinin phenotype on reaction with selected monoclonal antibodies while D had an "egg-like" phenotype. The viruses were administered at a dose of 1,000 TCD50 (for MDCK cells) by intranasal inoculation to groups of 27 or 28 volunteers. Viruses A, B, and C all produced disease in six to eight volunteers, whereas D produced no illness and only four volunteers were infected. The viruses shed by the volunteers were indistinguishable from those with which they were inoculated. The haemagglutinin genes of the viruses were sequenced and changes were detected indicating amino acid substitutions at position 196-198 in the attenuated egg-grown virus D whereby a potential glycosylation site present in the other viruses was lost. PMID- 2310305 TI - Cholesterol diet followed by normal diet alters functional and metabolic responses in rabbit aorta. AB - Male New Zealand rabbits were fed a high cholesterol (1%) diet for 8 weeks followed by a normal diet for 8 additional weeks. Rabbits on normal diet were used as controls. Serum cholesterol, elevated at the end of the cholesterol feeding period, returned to normal at the time of observation. Aortic wall lesions were severe and vessel wall cholesterol in the thoracic aorta was approximately 10 times the level in control animals. In vitro, thoracic aortic rings were used to measure contractile response to noradrenaline (NOR); no difference in response was found between normal and treated rabbits. Rings pre contracted with NOR, were exposed to acetylcholine (Ach), ATP and NaNO2. Proximal and distal rings from normal animals showed a dose-dependent relaxation response to all agents, though maximal dilation occurred at an intermediate concentration of Ach. The rings from treated rabbits relaxed normally in response to NaNO2, but ATP relaxation was reduced in proximal and distal rings and Ach induced a contractile response. HPLC analysis of tissue extracts from aortic arch and distal thoracic aorta showed reduced ATP, ADP, GTP and GDP, and increased AMP. These changes resulted in a reduced energy charge and a reduction in total adenine nucleotides. The data indicate that cholesterol feeding, followed by normal diet, causes severe alterations of aortic vessel wall and that at an advanced stage of the diet-induced experimental disease energy metabolism and endothelium dependent vasodilation remain impaired even in the presence of normal serum lipids. PMID- 2310307 TI - Magnetic resonance imaging and clinical correlates of intellectual impairment in myotonic dystrophy. PMID- 2310306 TI - Influence of cholesterol oxides on endocytosis of cultured endothelial and smooth muscle cells. AB - Human umbilical vein endothelial cells and rabbit aortic smooth muscle cells in culture were incubated for intervals up to 24 hrs with varying concentrations of cholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestane-3 beta,5 alpha,6 beta-triol or cholesterol-5 alpha, 6 beta-epoxide. Endocytosis, as measured by uptake of horseradish peroxidase (HRP), was inhibited in a dose and time dependent manner in both endothelial and smooth muscle cell cultures by cholestane-3 beta,5 alpha,6 beta-triol and 25-hydroxycholesterol. Inhibition by 7 ketocholesterol in endothelial cells occurred only at higher concentrations, and cholesterol and cholesterol epoxide showed no significant inhibitory effects. The viability of the cells exposed to the cholesterol oxides at the concentrations that inhibited the uptake of HRP was not changed. Cholesterol oxides induce functional endothelial injury, not morphologically apparent, which may be involved in atherogenesis. PMID- 2310308 TI - Significantly higher levels of soluble interleukin 2 in patients with relapsing remitting multiple sclerosis compared with healthy subjects. PMID- 2310309 TI - Serum interleukin 2 and soluble interleukin 2 receptor in patients with multiple sclerosis who are experiencing severe fatigue. PMID- 2310310 TI - Heritability of cognitive performance in aging twins. The National Heart, Lung, and Blood Institute Twin Study. AB - The genetic contribution to performance on scales designed to measure mild to moderate decrements in cognitive functioning in a population at risk is unknown. In the present analysis, 134 monozygotic and 133 dizygotic male twin pairs (mean age, 63 years) were given three cognitive tests: the Mini-Mental State examination, the Iowa Screening Battery for Mental Decline, and, for comparison, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale. The primary objective of the analysis was to test for a significant heritable component to performance on these measures. A secondary objective was to determine the extent to which shared variance with significant confounders such as education, age, and depression affects the outcome of the heritability analysis. Results indicate that performance on tests intended to measure cognitive decline in the elderly does have a significant genetic component and that these estimates tend to increase after adjustment for covariates. Heritability estimates adjusted for covariates were 30% for the Iowa Screening score, 60% for the Mini-Mental State score, and 67% for the Digit Symbol Substitution score. PMID- 2310311 TI - Myotonia fluctuans. AB - Autosomal-dominantly inherited nondystrophic myotonic disorders are an interesting group of muscle diseases that provide considerable opportunity for future molecular genetic studies to identify the genes responsible for specific membrane functions. A family with such a myotonic disorder is described with features that are distinctly different from myotonia congenita and paramyotonia congenita. Five members were affected in three generations. The myotonia fluctuated to an unusual degree. It did not worsen with cold but increased markedly with potassium loading. Muscle weakness never occurred. Analysis of the contraction force of the flexor digitorum muscle showed a unique type of myotonia, namely, exercise-induced delayed-onset myotonia. Microelectrode studies done on one muscle biopsy specimen revealed a normal chloride conductance of the muscle fiber membrane. PMID- 2310312 TI - Centronuclear myopathy and type-1 hypotrophy without central nuclei. Distinct nosologic entities? AB - Four infants presented with severe hypotonia, weakness, and hypoventilation or apnea at birth. Their clinical presentations and courses resembled those of the x linked recessive form of centronuclear myopathy. Histologic examination of their muscle biopsy specimens showed patterns ranging between centronuclear myopathy and type-1 hypotrophy without central nuclei. Regardless of their gender or the appearance of their biopsy specimens, the children all had a poor outcome. The clinical and biopsy findings in these infants suggest that centronuclear myopathy and type-1 hypotrophy without central nuclei do not represent distinct nosologic entities. It seems more likely that the histologic changes represent abnormalities in fiber size distribution and development, which are nonspecific and which reflect a primary defect at one or more sites in the neuraxis. PMID- 2310313 TI - Screening for cognitive impairment in multiple sclerosis. An evaluation of the Mini-Mental State Examination. AB - The usefulness of the Mini-Mental State Examination (MMSE) as a screening test for identifying cognitive impairment in patients with multiple sclerosis (MS) has been questioned because many patients who score above the suggested cutoff score of 24 exhibit severe focal or global cognitive deficits. We reevaluated the usefulness of the MMSE by studying 85 patients with clinically definite MS who also received an extensive battery of neuropsychological tests. Although scores on the MMSE were negatively correlated with the number of neuropsychological tests on which patients with MS displayed impairment, the MMSE was not sufficiently sensitive to identify precisely defined dementia in these patients. The MMSE was nonetheless a useful predictor of focal cognitive impairment, particularly in relapsing-remitting patients with relatively minor physical disabilities. Additional analyses suggested strategies for minor modifications of the MMSE that may improve its sensitivity and specificity for identifying dementia while preserving its major advantages as a screening examination: brevity and ease of administration and scoring. PMID- 2310314 TI - Sensory impairment in the hands secondary to spondylotic compression of the cervical spinal cord. AB - In a 5-year period, 11 patients with spondylotic compression of the cervical spinal cord presented with a clinical picture dominated by glove-distribution sensory loss in the hands. Compressive lesions in each case were documented by myelography. The hand sensory loss was often global, and in some patients the involvement extended proximally as far as the elbows. Motor findings in the hands were no more than mild to moderate, as were motor and sensory findings in the legs. Nine patients improved with surgical decompression. The syndrome may result from ischemia to the intrinsic border areas of collateralization between the superficial pial network and the central arterial supply to the cervical cord, although venous stagnation may also play a role. This clinical presentation should always raise the suspicion of a cervical myelopathy, which is potentially treatable. PMID- 2310315 TI - The search for causes of idiopathic intracranial hypertension. A preliminary case control study. AB - Idiopathic intracranial hypertension (pseudotumor cerebri) is a condition that occurs predominantly in obese women. It consists of elevated spinal fluid pressure, normal spinal fluid contents, papilledema, and headaches with normal imaging studies. Long lists of putative causes and associations have arisen, many consisting of individual case reports. We did a retrospective case-control study on 40 patients and 39 age- and sex-matched control subjects to examine the incidence of these associated conditions. Our results are only suggestive due to the small sample size; however, obesity and recent weight gain occurred more commonly in patients with idiopathic intracranial hypertension than in control subjects. All forms of menstrual abnormalities, incidence of pregnancy, antibiotic use, and oral contraceptive use were equal in both groups. A larger multicenter study will be needed to more completely characterize the risk factors for this condition. PMID- 2310316 TI - The thoracic outlet syndrome is underrated. PMID- 2310317 TI - The thoracic outlet syndrome is overdiagnosed. PMID- 2310318 TI - The changing paradigm of neurologic practice and care. Implications for the undergraduate curriculum. PMID- 2310319 TI - Neuropsychological correlates of bilateral amygdala damage. AB - We conducted an extensive neuropsychological investigation in a patient with bilateral amygdala damage due to Urbach-Wiethe disease. The patient had significant defects in nonverbal visual memory, in social behavior, and in "executive control" functions, findings consistent with the proposal, based on experimental animal work, that the amygdala plays important roles in memory and in the modulation of social and emotional behavior. General intellect and language were normal. A psychophysiological study showed that she had normal electrodermal activity (skin conductance responses), an important finding in view of the role that has been attributed to the amygdala in the central control of autonomic responses. PMID- 2310320 TI - Convergence nystagmus associated with Arnold-Chiari malformation. AB - A case of convergence nystagmus associated with an Arnold-Chiari type I malformation is presented. The nystagmus appeared in the absence of fixation, was provoked during Valsalva's maneuver and neck flexion and extension, and attenuated on deep inspiration. Sagittal magnetic resonance images showed that the diameter of the cerebral aqueduct increased with the neck in full flexion and in full extension. Surgical foramen magnum decompression considerably reduced the nystagmus and abolished the postural variation of aqueduct diameter. It is postulated that this nystagmus was due to a combination of mechanical distortion and abnormal transmission of cerebrospinal fluid pressure to the aqueductal region. PMID- 2310321 TI - Functional blindness in photorefractive keratectomy. PMID- 2310322 TI - Advanced cardiac life support certification in ophthalmology. PMID- 2310323 TI - Equations for Snellen equivalent. PMID- 2310324 TI - Magnetic resonance imaging and retinal tacks. PMID- 2310325 TI - Metabolic imaging of uveal melanoma using positron emission tomography. PMID- 2310326 TI - Chlamydial conjunctivitis and genital gonorrhea in pregnancy. PMID- 2310327 TI - Cervical spine dislocation presenting as an isolated Horner's syndrome. PMID- 2310328 TI - Retinal hamartoma in neurofibromatosis 2. PMID- 2310329 TI - Outcomeology. PMID- 2310330 TI - Vitamin A deficiency and xerophthalmia. PMID- 2310331 TI - Journal peer reviewing. Anonymity or disclosure? PMID- 2310332 TI - Corneal perforation in patients with vitamin A deficiency in the United States. AB - An emaciated alcoholic 52-year-old white woman presented with an old left corneal perforation and bilateral conjunctival and corneal xerosis. The serum vitamin A level was 0 mumol/L. Laboratory and radiologic findings were consistent with the diagnosis of a fat malabsorptive syndrome secondary to chronic alcoholic pancreatitis. Histopathologic evaluation of her enucleated globe revealed conjunctival epidermidalization, corneal perforation with prolapse and loss of intraocular contents, retinal detachment, and massive choroidal hemorrhage. A second patient presented with bilateral conjunctival xerosis, corneal ulcers, and a low serum vitamin A level. Corneal perforation of one ulcer ensued during her hospitalization. Medical investigation revealed hepatic metastases of an unknown primary source. Causes of vitamin A deficiency and its ocular complications as well as medical and surgical management options are discussed. PMID- 2310333 TI - Xerophthalmia and cystic fibrosis. AB - We treated two infants with failure to thrive who presented with clinical evidence of conjunctival and corneal xerosis. One patient was referred with possible infectious corneal ulcer thought to exist because there were deep peripheral ulcerations of the cornea and associated hypopyon. The other patient was initially thought to have a nasolacrimal duct obstruction because of excessive tearing. Xerophthalmia secondary to vitamin A deficiency was suspected and led to the diagnosis and treatment of cystic fibrosis in each case. Therapy with vitamin A promptly resolved the xerosis, but it also caused a transient rise in intracerebral pressure. Xerophthalmia can still be a problem in developed countries when underlying disorders, such as cystic fibrosis, lead to vitamin A malabsorption. PMID- 2310334 TI - Visual acuity loss in retinitis pigmentosa. Relationship to visual field loss. AB - We compared visual acuity with visual field radius in 235 patients with typical retinitis pigmentosa and no evidence of other visual acuity-limiting problems (such as cataract or foveal cystoid edema). Results show a strong relationship between visual acuity loss and proximity to the fovea of the visual field border (shortest distance from the foveal center to the border of the V-4-e isopter) for these patients. Ninety-six percent of patients with central visual field radii greater than 30 degrees have visual acuities of 20/40 or better; 32% of patients with central visual field radii smaller than 10 degrees have visual acuity of 20/40 or better. PMID- 2310335 TI - Combined phacoemulsification and pars plana vitrectomy. AB - Combined phacoemulsification and pars plana vitrectomy were performed in eight eyes with cataract and vitreoretinal disease. Six eyes had tractional retinal detachment and/or nonclearing vitreous hemorrhage, one eye had a retained metallic intraocular foreign body, and one eye had a traumatic retinal detachment. In six eyes, a posterior chamber lens implant was placed in the capsular bag. Postoperative visual acuity improved in each case and ranged between 20/15 and 6/200. There were no perioperative complications, and the posterior chamber lens implant appeared well tolerated during an average follow up interval of 8 months (range, 3 to 30 months). This technique allows endocapsular fixation of a posterior chamber lens and provides rapid visual rehabilitation with a single operation. PMID- 2310336 TI - Computer-assisted corneal topography in family members of patients with keratoconus. AB - In about 6% of patients with keratoconus, there is a history of familial disease. High keratometric astigmatism and mildly irregular mires observed by placidois disc have been suggested to represent variable forms of expression of a gene in family members of patients with keratoconus. We used a computer-assisted digital videophotokeratoscope to map the corneas of 28 family members of 5 patients with keratoconus. Abnormalities observed in family members included central steepening, greater steepening of the cornea inferior to the apex, and substantial asymmetry in the central dioptric power between the two eyes of the same individual. These findings were similar to, but less severe than, those found in patients with keratoconus and may represent the variable expression of a gene contributing to the development of keratoconus. Pedigree analysis in these families suggests an autosomal dominant mode of inheritance. PMID- 2310337 TI - Electrophysiological changes in juvenile diabetics without retinopathy. AB - Several components of the electroretinogram were studied in 31 juvenile diabetics and 15 age-matched normal controls. The diabetic group consisted of 18 patients without retinopathy and 13 with mild background retinopathy. Oscillatory potentials were measured at low-stimulation energies. Significantly reduced amplitudes and component-specific delayed peak implicit times were found in both diabetic groups compared with the data from the controls. Similar results were obtained in the photopic and scotopic electroretinogram. From these findings, we suggest that retinal dysfunction is already present in juvenile diabetics without photographic evidence of retinopathy after a mean duration of diabetes of 7 years. PMID- 2310338 TI - Eye injuries in children in Israel. A nationwide collaborative study. AB - A nationwide prospective collaborative study on ocular trauma was performed in Israel during a period of 3 years (1981 through 1983). Almost half of the traumas (1127 [47%] of 2416 eyes) were sustained by children younger than age 17 years, and mainly between the ages of 6 and 12 years. Most of the injuries happened at home (38.1%) or in the street (26.8%) and during play and sport (65.1%). The male to-female ratio among the children was 4:1. Blunt injuries accounted for 59.2%; 30.5% were perforating injuries and the rest were chemical and radiation injuries. The visual acuity at the time of hospital discharge was better than 6/30 in the majority of the eyes but 122 patients (11%) had a visual acuity of less than 6/60, and no light perception was the result in 40 eyes (3%). The reasons for the severe outcome were as follows: 23 eyes (2%) owing to phthisis, 22 eyes (1.9%) were enucleated, and 16 eyes (1.4%) suffered from endophthalmitis. PMID- 2310339 TI - Critical evaluation of the cocaine test in the diagnosis of Horner's syndrome. AB - We evaluated the effectiveness of the cocaine test for diagnosing Horner's syndrome. The test was administered to 119 patients with a diagnosis of Horner's syndrome and to 50 normal subjects. We compared the cocaine-induced anisocoria in the two groups by measuring photographs of the pupils. We found the cocaine test to be highly effective in separating normal subjects from patients with Horner's syndrome. The chances of having Horner's syndrome increased with the amount of cocaine-induced anisocoria. Through the use of logistic regression analysis, we determined the odds ratio of having Horner's syndrome compared with not having it for each 0.1-mm increment of anisocoria measured after cocaine administration. A postcocaine anisocoria value of 0.8 mm gave a mean odds ratio of approximately 1050:1 that Horner's syndrome was present (lower 95% confidence limit = 37:1). We found that simply measuring the postcocaine anisocoria provided a better prediction of Horner's syndrome than taking the trouble to calculate the net change in anisocoria. Odds ratios should help the clinician decide if the result of a cocaine test is indicative of Horner's syndrome. PMID- 2310340 TI - Management of congenital lacrimal sac fistula. AB - Fourteen patients who were treated for symptomatic congenital lacrimal sac fistula were retrospectively reviewed to evaluate surgical success. Excision of the fistula alone was performed on 9 patients and excision with nasolacrimal intubation on 5 patients (to our knowledge, the latter has not been previously described in the English literature). None of the 14 patients were symptomatic postoperatively during a mean follow-up of 16 months, with a range from 3 to 39 months. We conclude that dacryocystorhinostomy is usually not necessary to successfully treat symptomatic congenital lacrimal sac fistula. PMID- 2310341 TI - Nasolacrimal duct obstruction after endoscopic sinus surgery. AB - Intranasal endoscopic sinus surgery has several potential ocular complications, including visual loss, diplopia, retrobulbar hemorrhage, and epiphora. We treated eight patients with persistent nasolacrimal duct obstruction after endoscopic sinus surgery. All patients required dacryocystorhinostomy to achieve a patent lacrimal system drainage. To our knowledge, this is a previously unreported complication in the ophthalmologic literature. The relevant anatomy of the nasolacrimal duct is discussed in addition to surgical procedures for avoidance and treatment of iatrogenic injury to the system. Endoscopic sinus surgery is a highly successful procedure that is rapidly gaining popularity among otolaryngologists. As the number of patients undergoing this type of surgery increases, an increase in the relative number of ocular complications should be anticipated. PMID- 2310342 TI - Quantitative regional structure of the normal human lamina cribrosa. A racial comparison. AB - We digitized magnified photographs of cross-sections of the laminae cribrosae of 16 normal subjects 50 or more years of age. The sample included 7 blacks and 9 age-matched whites. Connective tissue area as a proportion of the lamina cribrosa area was significantly less and pores were significantly larger in the superior and inferior than in the nasal and temporal quadrants of the lamina cribrosa. These differences were more pronounced for peripheral as compared with central regions of the lamina cribrosa. Less connective tissue support for nerve fibers in the superior and inferior quadrants of the optic nerve head could contribute to their greater susceptibility to glaucoma damage by allowing greater distortion of these regions at elevated intraocular pressures. The least connective tissue support was present in the inferoperipheral region of the lamina cribrosa, which may be related to the greater frequency of superior visual field defects in glaucoma. Blacks had larger total lamina cribrosa area, indicating a larger optic nerve head, and also a greater number of laminar pores than whites. However, the connective tissue proportion and pore size distribution in the laminae cribrosae of blacks were almost identical to those of whites. We found no evidence suggesting that the greater susceptibility of blacks to glaucoma damage is due to less connective tissue support for nerve fibers passing through their laminae cribrosae than in whites. PMID- 2310343 TI - Trazodone-induced palinopsia. AB - Palinopsia refers to the persistence or reappearance of an image of a recently viewed object. Typically, patients with palinopsia have other visual symptoms or signs, and the underlying cause is a structural lesion of the posterior portions of the cerebral hemispheres. However, we treated three patients who experienced palinopsia as an isolated symptom, apparently as a side effect of trazodone hydrochloride therapy for depression. The palinopsia was dose related and disappeared with reduction or cessation of therapy. PMID- 2310344 TI - A 32-year follow-up of the rigid Schreck anterior chamber lens. A clinicopathological correlation. AB - We describe the clinicopathological findings in an eye after 32 years of successful anterior chamber lens implantation. In 1956, a rigid Schreck total polymethylmethacrylate anterior chamber lens was implanted in the right eye of a 28-year-old white man 1 year after corneo-scleral laceration with traumatic cataract. The postoperative clinical course was subjectively unremarkable for at least 30 years. In 1988, the patient developed secondary angle closure glaucoma, associated with a cavernous Schnabel optic atrophy that was caused by peripheral anterior synechiae and fibrovascular downgrowth into the anterior chamber. The lens implant was encapsulated "cocoonlike." Secondary proliferation of corneal endothelial cells covered the fibrous membrane and the chamber angle structures. No inflammatory reaction and only a very slight foreign-body reaction in the area of the footplate of the anterior chamber lens were present. Clinical and histopathological findings indicate that polymethylmethacrylate is sufficiently inert and biocompatible to be tolerated by the surrounding ocular tissues for more than 30 years. PMID- 2310345 TI - Vitreous cefazolin levels after intravenous injection. Effects of inflammation, repeated antibiotic doses, and surgery. AB - We devised a standardized rabbit model of intraocular inflammation using heat killed Staphylococcus epidermidis as the inducing organism. We applied this model to study the effects of (1) inflammation, (2) repeated antibiotic doses, and (3) surgical status of the eye on cefazolin levels in the vitreous cavity after intravenous administration. Intravenous cefazolin sodium, 50 mg/kg, was administered every 8 hours for 48 hours. Eyes were harvested for assay of vitreous cavity antibiotic levels at various intervals from 1 to 49 hours. Drug levels were compared in inflamed and noninflamed eyes under both phakic and aphakic/vitrectomized conditions. At 1 hour, levels in phakic specimens were 3.0 mg/L in inflamed eyes vs undetectable in noninflamed eyes (P less than .01), but progressively increased to 10.6 mg/L at 49 hours (P less than .02) in inflamed eyes only. Levels in aphakic/vitrectomized eyes at 1 hour were 6.7 mg/L in inflamed eyes vs 4.2 mg/L in noninflamed eyes (P less than .1), but progressively increased to 24.9 mg/L at 49 hours (P less than .001) in inflamed eyes only. Levels at 49 hours in inflamed phakic and inflamed aphakic/vitrectomized eyes were well above the minimum inhibitory concentrations for organisms termed sensitive to cefazolin. We would conclude, therefore, that repeated doses of intravenous cefazolin may play an important adjunctive role in the treatment of endophthalmitis. PMID- 2310347 TI - Posterior corneal depression. PMID- 2310346 TI - Ultrastructural localization of extracellular matrix components in human retinal vessels and Bruch's membrane. AB - We have used the electron microscopic immunogold technique to localize precisely various extracellular matrix components in human retinal vessels and Bruch's membrane. Collagen types IV and V, laminin, and heparan sulfate proteoglycan core protein were localized in basement membranes of retinal capillaries. In addition to the capillary basement membrane components, collagen types I and III and fibronectin were found in the basement membranes of retinal arterioles and venules. The basement membranes of choriocapillaries and retinal pigment epithelial cells in Bruch's membrane also showed a similar distribution of the retinal capillary basement membrane components. Both the inner and outer collagenous layers of Bruch's membrane contained collagen types I and III along with fibronectin, whereas collagen type VI was mostly limited to the central elastic lamina. The precise localization and distribution of various extracellular matrix components in human retinal vessels and Bruch's membrane may be important for understanding their normal function as well as their alteration in disease. PMID- 2310348 TI - The tight retracted lower eyelid. AB - Grave's ophthalmopathy, anophthalmia, trauma, surgery, burns, and skin disorders can result in lower eyelid retraction. The retracted lower eyelid is tight in contrast to the lax lower eyelid of the common involutional ectropion. Cicatrization of the skin and muscle produces the prototype cicatricial ectropion. Downward traction on all layers of the lid rather than cicatrization causes lower eyelid retraction. Sixty-one retracted lower eyelids were surgically repaired without a skin graft in 40 patients. In the new technique, the retracted lower lid is repaired by releasing the lower eyelid retractors from their tarsal attachment. A lateral canthoplasty and lower lid prezygomatic flap anchored to the orbital periosteum support the released lower eyelid. PMID- 2310349 TI - Difficulties with speech intelligibility in noise in spite of a normal pure-tone audiogram. AB - A group of 15 patients with complaints of having difficulties in understanding speech, especially in noisy surroundings in spite of (nearly) normal pure-tone audiograms, was subjected to a battery of speech-audiometric tests. The results showed that these subjects had a statistically significantly higher speech reception threshold (SRT) for sentences in noise than a reference group of 10 normal-hearing subjects. This difference was most clear for a fluctuating masking noise. In conditions with much reverberation, the patients also proved to be handicapped more than the control group. Binaural hearing gain was equal for both groups. The pathogenesis of the speech-hearing loss is not known, but assessment of the SRT in noise proves to be a valuable asset in objectifying these patients' complaints. PMID- 2310350 TI - Effect of stimulus parameters on auditory brainstem response spectral analysis. AB - A recent increase of interest in spectral analysis has been prompted by the suggestion that spectral components of the ABR may contribute to differential diagnosis. Knowledge of the effects of stimulus parameters on the spectral content of the ABR is essential. The present study examined the effect of intensity, rate, and polarity on the spectral content of ABRs of 15 normal hearing subjects. The effects of intensity were significant at all spectral frequencies examined while the effects of rate and polarity were frequency specific. These results indicate that the effects of stimulus parameters must be considered in examining the ABR spectral analysis. PMID- 2310351 TI - Monaural versus binaural auditory brainstem response threshold to clicks masked by high-pass noise in normal-hearing subjects. AB - Monaural and binaural auditory brainstem response (ABR) thresholds to clicks masked by high-pass noise with a cut-off frequency of 1,590 Hz were measured in normal-hearing subjects. In sleeping normal-hearing subjects, the 1,000-Hz frequency-specific ABR threshold for binaural stimulation amounted to 12 dB nHL and for monaural stimulation to 18 dB nHL. No significant difference in latency was found between monaural and binaural stimulation. Binaural ABR threshold was 5.5 +/- 1.4 dB (mean +/- SEM) lower than the mean monaural ABR threshold. This difference is statistically significant (Student's t test; p less than 0.005). PMID- 2310352 TI - Tinnitus with normal hearing sensitivity: extended high-frequency audiometry and auditory-nerve brain-stem-evoked responses. AB - Extended high-frequency (HF) audiometry and auditory-nerve brain-stem-evoked responses (ABR) were carried out on two groups of subjects with normal hearing sensitivity. The experimental group comprised 17 subjects with tinnitus, while the control group consisted of age- and sex-matched subjects, not suffering from tinnitus. The aim of the study was to determine whether extended HF audiometry or ABR might reveal significant differences between these two groups of subjects with normal hearing sensitivity. In addition, the characteristics of tinnitus in subjects with normal audiograms were discussed. The results of extended HF audiometry showed no significant differences between the subjects with and without tinnitus. The ABR parameters considered were also within normal limits bilaterally. Based on the methods employed in this study, tinnitus in normal listeners does not appear to reflect appreciable damage in the cochlea or in the brain-stem auditory pathways. The authors present some suggestions for future research. PMID- 2310353 TI - Stapedius reflex growth function in cochlear implant patients. AB - The growth function of the contralateral stapedius reflex elicited by analog electrostimulation via cochlear implant was investigated in 9 patients and compared to reflex functions obtained for acoustic stimulation in 3 normal hearing subjects. Sinusoidal signal bursts with the same time pattern were used for the two stimulation modes, the contraction of the middle ear muscle was monitored by sampling the compliance change in the contralateral ear. The reflex amplitudes were found to increase with increasing stimulus intensity in all individuals except in 1 with electrical stimulation. The slope of the intensity function for electrostimulation ranged between 5 and 85%/dB and in the acoustical mode between 2 and 4%/dB. In case of electrostimulation a frequency effect was observed. PMID- 2310354 TI - Perilymphatic fistula in the guinea pig. AB - Clinical reports on perilymphatic fistulae (PLF) of the round window membrane (RWM) have shown different degrees of hearing loss. However, the hearing can also be entirely unaffected. Experimentally induced PLF of the RWM in animals showed results similar to those of the clinical reports, although some researchers have concluded that perforation of the RWM per se does not necessarily induce significant hearing loss. The purpose of the present study was to clarify if, and how, PLF of RWM in the guinea pig actually affects the auditory action potentials. During 1 h of observation following perforation of the RWM, the immediate and continuous effect of the PLF was evaluated. In more than 50% of the animals, different amounts of threshold shift were obtained. In another group of guinea pigs an attempt was made to clarify the findings by reducing the cerebrospinal fluid pressure before perforating the RWM. PMID- 2310355 TI - Frequency selectivity and temporal resolution in patients with various inner ear disorders. AB - Both frequency selectivity and temporal resolution were examined in patients with various inner ear disorders. These included noise-induced hearing loss (n = 24), Meniere's disease (n = 16), sudden deafness (n = 25), toxic inner ear damage (n = 14), presbyacusis (n = 38) and degenerative progressive inner ear hearing loss (n = 8). To facilitate quantitative comparison, various factors were introduced, namely, frequency resolution factor (FRF), temporal resolution factor (TRF) and a combined resolution factor (FTRF). The FRF of normal-hearing subjects in background noise conditions was found to be approximately 20% less than in comparative test conditions without noise, whereas the TRF of normal-hearing persons tested under background noise conditions showed a remarkable increase (factor 3). The frequency resolution performance and/or the temporal resolution performance were found to be impaired in all patient groups with inner ear hearing loss. This is particularly noticeable for temporal resolution in test conditions involving the addition of background noise. It can be concluded that in such cases, speech discrimination can be seriously jeopardized. PMID- 2310356 TI - Physiologic correlates of protection afforded by anti-G suits. AB - A new uniform-pressure pneumatic anti-G suit (UPS) was compared with the standard CSU-13B/P anti-G suit, using measurements of: blood lactate, heart rate changes, and segmented lower-body blood pooling (by impedance plethysmography). Subjects were exposed to a series of gradual-onset-rate (GOR) runs (0.1 G.s-1), rapid onset-rate (ROR) runs (6 G.s-1), and simulated aerial combat maneuvers (SACM) on the USAF School of Aerospace Medicine human-use centrifuge. All measured parameters and subjective reports indicated that increased protection was afforded by the UPS. The impedance plethysmography measurements indicated that prevention of blood pooling in all lower-body segments is the predominant mechanism whereby uniform pressure permits significantly longer times-to-fatigue during SACMs. PMID- 2310357 TI - Vascular response of retinal arteries and veins to acute hypoxia of 8,000, 10,000, 12,500, and 15,000 feet of simulated altitude. AB - Computerized scanning microdensitometry of fundus photographs was used to study the effect of acute hypoxia on vessel diameters of 238 retinal arteries and 227 veins in 40 men aged 18-23 years. Fundus photography was performed at sea level and at simulated altitudes in a low-pressure chamber, randomly selecting 10 men to each of four altitudes--8,000, 10,000, 12,500, and 15,000 ft (2,400, 3,000, 3,800, and 4,500 m). After 15 min of hypoxic exposure, the caliber of small arteries (less than 75 microns) increased 4% (p less than 0.01) and that of large arteries (greater than or equal to 75 microns) 7% (p less than 0.05), already at 8,000 ft (2,400 m). The caliber of large veins did not change until an increase of 6% (p less than 0.01) was observed at 15,000 ft (4,500 m). Although large arteries increased 7% (p less than 0.05) and 8% (p less than 0.01) in diameter at 10,000 ft (3,000 m) and 15,000 ft and small veins 9% (p less than 0.05) and 12% (p less than 0.01) at the same altitudes, respectively, no change was observed at 12,500 ft (3,800 m). Thus, the dilating effect of hypobaric hypoxia was nonlinear from sea level to 15,000 ft of simulated altitude. As an overall response to the four simulated altitudes the vasodilation was negatively correlated to the vessel diameter at sea level (r = -0.20) in both arteries and veins (p less than 0.01). The variability of hypoxic vascular response was as great within different parts of individual retinas as between different retinas. PMID- 2310358 TI - The role of smooth pursuit in suppression of post-rotational nystagmus. AB - Some authors have suggested that the smooth pursuit system (SPS) may be responsible for nystagmus suppression when a small visual target--stationary with respect to a subject receiving vestibular stimulation in the dark--is presented. Under five experimental conditions, post-rotational vestibular stimulations were combined in different ways with the presentation of a small visual target. The oculomotor responses of 15 normal subjects were recorded and analyzed. The characteristics of nystagmus suppression (latency, dynamics, and nonlinear behaviour) seem to be consistent with the hypothesis of SPS participation. A nonlinear mathematical model of the interaction between vestibulo-ocular reflex and SPS is presented. Computer simulation of the experimental conditions considered in this study provides theoretical results which closely approximate the actual experimental data. PMID- 2310359 TI - Effect of spectral flash on readaptation time. AB - The effects of an adapting flash of different colors on human vision were investigated with various flashes and target luminances. The readaptation time (RAT) was measured using optokinetic nystagmus elicited by a projected moving striped pattern in a hemisphere. The RATs were recorded from 26 subjects with a multichannel pen recorder. Two target luminances (1.1 X 10(-5) cd/m2 and 2.6 X 10(-5) cd/m2) and 12 flash wavelengths (449 nm, 456 nm, 468 nm, 477 nm, 498 nm, 502 nm, 520 nm, 565 nm, 580 nm, 591 nm, 622 nm, and 703 nm) were used. A spectral RAT curve was obtained, which showed that the chromatic response of RAT follows this order: green greater than blue greater than yellow greater than red. A larger influence of the variation of the target luminance on the RAT was demonstrated at shorter wavelengths. The results also showed that the energy density of the flash has a larger variation with the RAT in blue and green than in red. PMID- 2310360 TI - Trends and individual differences in response to short-haul fight operations. AB - A survey of airline pilots was undertaken to determine normative patterns and individual differences in mood and sleep during short-haul flight operations. The results revealed that over the course of a typical 2-d trip, pilots experience a decline in positive mood, or activity, and an increase in negative mood, or tension. On layovers, pilots report experiencing sleep of shorter duration and poorer quality than at home. These patterns are very similar to those reported by Gander and Graeber and by Gander et al. using high-fidelity sleep and activity monitoring equipment. Examination of the impact of two personality dimensions extracted from the Jenkins Activity Survey measure of the Type A personality, Achievement Striving and Impatience/Irritability, suggested that Impatience/Irritability may serve as a marker of individuals most likely to experience health-related problems on trips. Achievement Striving may serve as a predictor of performance in crew settings. PMID- 2310361 TI - Moderate exercise and hemodilution during sleep deprivation. AB - The effect of 52 h of sleep deprivation (SD) upon blood constituents was studied in 12 young women aged 21.5 +/- 0.4 years. Subjects were individually isolated without time cues, performing a sequence of cognitive tasks. Significant decreases in hematocrit (p less than 0.002) and red cell count (p less than 0.04) developed, mainly over the first 28 h of SD, reaching a subsequent plateau or partial recovery. The calculated plasma volume also increased by 10.7 +/- 3.1% at 52 h, with recovery to a 6.9 +/- 3.2% increase the following day. About 1 L of water was retained over the first 30 h of SD, with a subsequent partial elimination of this excess. Plasma albumin and total protein concentrations were largely sustained in the face of the plasma expansion. The plasma pH showed a progressive fall from a baseline value of 7.381 +/- 0.014 to 7.332 +/- 0.006 at 52 h, while plasma bicarbonate decreased from a baseline figure of 31.2 +/- 0.7 to 26-27 mM/L (p less than 0.05). After 8 weeks, all subjects repeated the experiment, with the introduction of 30 min of exercise in the 40th h of wakefulness. Hematocrit and plasma volume changes were similar to those of the first experiment up to the time of exercise, but hematocrit decreased and plasma volume increased after the exercise bout, rather than reaching a plateau. Plasma pH increased with exercise, but returned to the previous low level at 52 h. Any arousing effect of the exercise bout was transient. The plasma expansion reflects metabolic and/or respiratory acidosis, plus possible effects of a prolonged period without recumbency. PMID- 2310362 TI - Functional endoscopic sinus surgery in aviators with recurrent sinus barotrauma. AB - Recurrent sinus barotrauma in an aviator is difficult to treat successfully. Exacerbations frequently result in marked aviator discomfort, cycles of temporary restriction from aviation duties, or even permanent disqualification for flying duties. Medical management and standard sinus operations are often ineffective, seldom curative, and have a disappointing record in returning the aviator to flying duties. Detailed computerized tomographic scanning of the paranasal sinuses coupled with the functional endoscopic sinus surgery approach directs treatment at the causative pathology. Sinus ventilation is improved while making possible a return to active flight status without recurrence of sinus barotrauma. Initial experience with the functional endoscopic sinus surgery technique in such a patient population is reported. A discussion of recurrent sinus barotrauma, paranasal sinus anatomy, and the theory of endoscopic surgical management for sinus disease is included. PMID- 2310363 TI - Medical impact analysis for the space station. AB - Since the Space Station Health Maintenance Facility can house only a relatively limited quantity of supplies and equipment, the decisions about what should be included must be based on documented research. In this study, Space Station medical care priorities were determined by a medical impact analysis of two analog populations, U.S. Army and U.S. Navy personnel. Diseases and injuries in the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) were ranked, using a Medical Impact Score (MIS) combining modified incidence rate and a function of disease outcome. The validity of the analysis method was tested by measuring rank order correlation between the two analog populations. Despite virtually identical age and sex distributions, Army and Navy incidence rates differed significantly for half of the ICD-9-CM categories, p less than 0.05. Disability rates differed for 76%, p less than 0.05. Nevertheless, Army and Navy MIS rank orders for categories and sections were not significantly different, p less than 0.001. In critical ways, the Space Station will be a safer environment than Earth. Cardiac events, musculoskeletal injuries, affective psychoses, and renal calculi were among the highest scoring categories. PMID- 2310364 TI - Case from the aerospace medicine residents' teaching file. Case #35. Renal cell carcinoma in an aviator with a long history of renal lithiasis. AB - This case study discusses the presentation, evaluation, and aeromedical disposition of an aviator with renal cell carcinoma, a disease seldom seen in the military flying population. It emphasizes the necessity of flight surgeon awareness of preventive medicine aspects of waivered medical disorders. PMID- 2310365 TI - Bright solar system objects, and ocular sensitivity. PMID- 2310366 TI - Cerebral tissue oxygen status and psychomotor performance during lower body negative pressure (LBNP). AB - Cerebral oxygen sufficiency was studied noninvasively, using multiwavelength near infrared spectrophotometry, in eight subjects exposed to lower body negative pressure (LBNP) of up to -90 mm Hg to induce presyncopal symptoms and signs. LBNP caused only small changes in the forebrain measures until the last 60 s of the exposures, whereupon oxyhemoglobin (HbO2) and oxidised cytochrome c oxidase fell, reduced hemoglobin (Hb) rose slightly, and the tissue blood volume (HbO2 + Hb) fell. In subjects showing presyncope, these changes anticipated the onset of a terminal bradycardia by some 20 s and may provide the trigger for cardiovascular decompensation, while the cessation of LBNP led to an overshoot in cerebral blood volume suggestive of a reactive hyperemia. Psychomotor testing showed a significant slowing of reaction time with LBNP, but only for the easiest component of a complex task, while saccadic latencies were found to be shortened following LBNP exposure. PMID- 2310367 TI - The N-acetylgalactosamine residue of exogenous GM2 ganglioside is recycled for glycoconjugate biosynthesis in rat liver. AB - A metabolic recycling of N-acetylgalactosamine (GalNAc), liberated from exogenous GM2 ganglioside [nomenclature of Svennerholm (1964) J. Lipid Res. 5, 145-155; IUPAC-IUB recommendations (1977) Lipids 12, 455-468], is demonstrated in rat liver. After the injection of a GM2 ganglioside isotopically radiolabelled on the terminal GalNAc residue ([GalNAc-3H]GM2), the liver retained a large amount of radioactivity distributed among: (1) a glycoprotein/glycosaminoglycan fraction, (2) a ganglioside fraction; and (3) a free-sugar fraction. Furthermore, volatile radioactivity was also found. The relative incorporation in the above fractions was time-dependent. The glycoprotein/glycosaminoglycan fraction contained radioactivity that was located on the GalNAc and GlcNAc residues. The ganglioside fraction was composed of two main families: gangliosides formed by a recycling of the liberated GalNAc, and gangliosides derived by direct utilization of the administered GM2. The free-sugar fraction contained mainly GalNAc. We suggest that GalNAc, after being released in the course of intra-lysosomal ganglioside catabolism, crosses the lysosomal membrane and passes into the cytosol, where the part not degraded is re-utilized for the biosynthesis of the different glycoconjugate classes. PMID- 2310368 TI - The effects of tumour necrosis factor-alpha (cachectin) and tumour growth on hepatic amino acid utilization in the rat. AB - The effects of acute administration of tumour necrosis factor-alpha (cachectin) (TNF-alpha) or of malignant tumour growth (Walker-256 carcinosarcoma) on hepatic availability and uptake of individual amino acids were compared. The results show that, in spite of lowering the hepatic availability of alanine, aspartate, serine, glycine and proline, the cytokine increased both the total amino acid hepatic uptake and the individual uptakes of alanine, glutamate, serine, threonine, proline, lysine and arginine, while decreasing those of leucine, isoleucine and phenylalanine. Tumour burden resulted in an increase in the hepatic availability of glutamine, threonine, glycine, lysine, leucine, isoleucine, valine and phenylalanine. Total liver amino acid uptake was unaffected, whereas the individual uptakes of alanine, threonine and proline were increased and those of glutamate, glutamine, serine and leucine were decreased. When effects of the cytokine are compared with those induced by tumour growth, there are similar increases in net utilization for alanine, proline and leucine, and a 3-fold difference in the increase observed for threonine. Unmatched effects are seen for glutamate, glutamine, aspartate, glycine, lysine, arginine, valine, phenylalanine and serine. PMID- 2310369 TI - A new method to monitor Kupffer-cell function continuously in the perfused rat liver. Dissociation of glycogenolysis from particle phagocytosis. AB - In order to study particle phagocytosis and glycogenolysis simultaneously, this study was designed to develop a direct-read-out method to monitor Kupffer-cell function continuously, based on the uptake of colloidal carbon by the isolated perfused rat liver. Livers were perfused for 20 min with Krebs-Henseleit buffer saturated with O2/CO2 (19:1). Colloidal carbon (1-2 mg/ml) was added to the buffer, and absorbance of carbon was monitored continuously at 623 nm in the effluent perfusate. Since colloidal-carbon uptake was proportional to A623, rates of uptake were determined from the influent minus effluent concentration difference, the flow rate and the liver wet weight. Rates of colloidal-carbon uptake were 50-200 mg/h per g and were proportional to the concentration of carbon infused. Data from light-microscopy and cell-separation studies demonstrated that carbon was taken up exclusively by non-parenchymal cells and predominantly by Kupffer cells. Further, the amount of colloidal carbon detected histologically in non-parenchymal cells increased as the concentration of colloidal carbon in the perfusate was elevated. When Kupffer cells were activated or inhibited by treatment with endotoxin or methyl palmitate, carbon uptake was increased or decreased respectively. Taken together, these results indicate that Kupffer-cell function can be monitored continuously in a living organ. This new method was utilized to compare the time course of phagocytosis of carbon by Kupffer cells and carbohydrate output by parenchymal cells. Carbohydrate output increased rapidly by 69 +/- 9 mumol per g within 2-4 min after addition of carbon and returned to basal values within 12-16 min. However, carbon uptake by the liver did not reach maximal rates until about 15 min. Infusion of a cyclo oxygenase inhibitor, aspirin (10 mM), caused a progressive decrease in carbohydrate output and blocked the stimulation by carbon completely. Aspirin neither altered rates of carbon uptake nor prevented stimulation of carbohydrate release by addition of N2-saturated buffer. The data from these experiments are consistent with the hypothesis that output of mediators by Kupffer cells, presumably prostaglandin D2 and E2, occurs transiently as Kupffer cells begin to phagocytose foreign particles in the intact organ, a process which continues at high rates for hours. PMID- 2310370 TI - Inhibitory action of cyclobutyrol on the secretion of biliary cholesterol and phospholipids. AB - A number of organic anions are known to decrease biliary secretion of cholesterol and phospholipid without affecting bile acid secretion. Cyclobutyrol (CB) is a choleretic agent which also inhibits biliary lipid secretion. Using isolated perfused rat liver we have studied this inhibition in relation to possible mechanisms suggested for other anions. Shortly after its administration to the isolated perfused liver, CB decreases biliary outputs of cholesterol and phospholipid, without changes in bile acid secretion, at low (450 nmol/min), high (1350 nmol/min) and nil taurocholate infusion rates. The absolute inhibition does not appear to be decreased by elevated bile acid secretion. There is a differential effect on secretion of cholesterol and phospholipid, more marked at low bile acid secretion rates. Biliary outputs of the canalicular membrane enzymes 5'-nucleotidase and alkaline phosphodiesterase I are also depressed by CB administration, but the anion does not affect the biliary output of bovine serum albumin or the output of rat serum albumin into the perfusion fluid. Since CB does not inhibit intracellular vesicular transport or apparently inhibit intracanalicular events, its effect is different from the effect of several other anions. From these studies it appears that the most likely effect of CB is exerted at the level of the canalicular membrane. PMID- 2310371 TI - Characterization of a specific form of protein kinase C overproduced by a C3H 10T1/2 cell line. AB - Murine embryo fibroblasts (C3H 10T1/2) which were genetically engineered to overproduce the beta 1 isoform of protein kinase C (PKC-beta 1) were used to obtain homogeneous preparations of PKC-beta 1 for the purpose of characterizing the specific structural and functional properties of this isoform. Fractionation of PKC activity from these cells by hydroxyapatite chromatography produced one major peak, which represented 93% of the total cellular PKC activity and was not detected in control cells. This major peak of activity was shown by Western blotting analysis with a beta 1-specific antiserum to be the overproduced beta 1 isoform, and exhibited a band at 77 kDa. The functional properties of the overproduced PKC-beta 1 were established with regard to phospholipid-dependence, Ca2(+)-dependence, responsiveness to a phorbol ester tumour promoter, activation by arachidonic acid (plus Ca2+), and inhibition by known PKC inhibitors. From these studies we conclude that PKC-beta 1 overproduced by C3H 10T1/2 cells exhibits the structural and functional properties previously ascribed to native PKC. Furthermore, these data provide the first definitive biochemical characteristics of this isoform of PKC. PMID- 2310372 TI - The size of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores depends on inositol 1,4,5-trisphosphate concentration. AB - An explanation of the complex effects of hormones on intracellular Ca2+ requires that the intracellular actions of Ins(1,4,5)P3 and the relationships between intracellular Ca2+ stores are fully understood. We have examined the kinetics of 45Ca2+ efflux from pre-loaded intracellular stores after stimulation with Ins(1,4,5)P3 or the stable phosphorothioate analogue, Ins(1,4,5)P3[S]3, by simultaneous addition of one of them with glucose/hexokinase to rapidly deplete the medium of ATP. Under these conditions, a maximal concentration of either Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 evoked rapid efflux of about half of the accumulated 45Ca2+, and thereafter the efflux was the same as occurred under control conditions. Submaximal concentrations of Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 caused a smaller rapid initial efflux of 45Ca2+, after which the efflux was similar whatever the concentration of Ins(1,4,5)P3 or Ins(1,4,5)P3[S]3 present. The failure of submaximal concentrations of Ins(1,4,5)P3 and Ins(1,4,5)P3[S]3 to mobilize fully the Ins(1,4,5)P3-sensitive Ca2+ stores despite prolonged incubation was not due either to inactivation of Ins(1,4,5)P3 or to desensitization of the Ins(1,4,5)P3 receptor. The results suggest that the size of the Ins(1,4,5)P3 sensitive Ca2+ stores depends upon the concentration of Ins(1,4,5)P3. PMID- 2310374 TI - Primary structure of a constituent polypeptide chain (AIII) of the giant haemoglobin from the deep-sea tube worm Lamellibrachia. A possible H2S-binding site. AB - The deep-sea tube worm Lamellibrachia, belonging to the Phylum Vestimentifera, contains two giant extracellular haemoglobins, a 3000 kDa haemoglobin and a 440 kDa haemoglobin. The former consists of four haem-containing chains (AI-AIV) and two linker chains (AV and AVI) for the assembly of the haem-containing chains [Suzuki, Takagi & Ohta (1988) Biochem. J. 255, 541-545]. The tube-worm haemoglobins are believed to have a function of transporting sulphide (H2S) to internal bacterial symbionts, as well as of facilitating O2 transport [Arp & Childress (1983) Science 219, 295-297]. We have determined the complete amino acid sequence of Lamellibrachia chain AIII by automated or manual Edman sequencing. The chain is composed of 144 amino acid residues, has three cysteine residues at positions 3, 74 and 133, and has a molecular mass of 16,620 Da, including a haem group. The sequence showed significant homology (30-50% identity) with those of haem-containing chains of annelid giant haemoglobins. Two of the three cysteine residues are located at the positions where an intrachain disulphide bridge is formed in all annelid chains, but the remaining one (Cys-74) was located at a unique position, compared with annelid chains. Since the chain AIII was shown to have a reactive thiol group in the intact 3000 kDa molecule by preliminary experiments, the cysteine residue at position 74 appears to be one of the most probable candidates for the sulphide-binding sites. A phylogenetic tree was constructed from nine chains of annelid giant haemoglobins and one chain of vestimentiferan tube-worm haemoglobin now determined. The tree clearly showed that Lamellibrachia chain AIII belongs to the family of strain A of annelid giant haemoglobins, and that the two classes of Annelida, polychaete and oligochaete, and the vestimentiferan tube worm diverged at almost the same time. H.p.l.c. patterns of peptides (Figs. 4-7), amino acid compositions of peptides (Table 2) and amino acid sequences of intact protein and peptides (Table 3) have been deposited as Supplementary Publication SUP 50154 (13 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1990) 265, 5. PMID- 2310373 TI - The high content of natural suppressor serine tRNA in dystrophic mouse muscle. AB - In order to gain an insight into the pathogenesis of mouse muscular dystrophy, we investigated the natural suppressor serine tRNA. The natural suppressor seryl tRNA was distinguished from the other seryl-tRNAs on the basis of its specific property of being converted into phosphoseryl-tRNA by a tRNA kinase. On a wet weight basis, the content of total tRNA in dystrophic muscles was 47% of that in normal muscles. Although the serine-accepting activities of tRNA were similar in muscles of 3-month-old dystrophic and normal mice, the ratio of [32P]phosphoseryl tRNA (suppressor tRNA) to the total serine tRNA was significantly enhanced in dystrophic muscles compared with that in normal muscles. This high content of suppressor tRNA in dystrophic muscles was further confirmed by dot-blot hybridization experiments with the DNA probes CGTAGTCGGCAGGAT and CGCCCGAAAGGTGGAA for major tRNA(IGASer) and suppressor tRNA respectively. At the early postnatal age of 3 weeks, when only a week had elapsed since the first manifestation of the dystrophic symptom (hindleg dragging), the ratio of suppressor tRNA to major tRNAs in dystrophic hindleg muscles was abnormally increased. Thereafter it decreased with age in normal mice but remained almost unchanged in dystrophic mice. Consequently, at 3 months old, it was 1.7 times higher in dystrophic than in normal mice. The suppressor tRNA is now accepted to play a role in the synthesis of glutathione peroxidase. The present study showed that the content of this enzyme was abnormally elevated in dystrophic mice. Previously we had demonstrated that the docosahexaenoic (C22:6) acid content in phospholipids was decreased, possibly resulting from the enhanced oxidative milieu caused by the dystrophic condition. Thus far, the findings suggest that an increase in the contents of suppressor tRNA and glutathione peroxidase in dystrophic muscle may have been secondarily induced by such a highly oxidative state in the dystrophic condition. However, it is difficult to exclude the possibility that the natural suppressor tRNA plays a primary role in the pathogenesis of muscular dystrophies. PMID- 2310375 TI - Inhibition of the alpha-L-arabinofuranosidase III of Monilinia fructigena by 1,4 dideoxy-1,4-imino-L-threitol and 1,4-dideoxy-1,4-imino-L-arabinitol. AB - 1. 1,4-Dideoxy-1,4-imino-L-threitol was synthesized and the synthesis of 1,4 dideoxy-1,4-imino-L-arabinitol was improved. 2. Both compounds are competitive inhibitors of Monilinia fructigena alpha-L-arabinofuranosidase III, the additional hydroxymethyl group in the arabinitol contributing about 17.8 kj/mol (4.25 kcal/mol) to the Gibbs free energy of binding. 3. The affinities (1/Ki) of both compounds vary with pH in a classical bell-shaped way, the pKa value being that of the acid-catalytic group on the enzyme [5.9; Selwood & Sinnott (1988) Biochem. J. 254, 899-901] and the pKb values being those of the free inhibitors, 7.6 and 7.8 respectively. 4. On the basis of these and literature data we suggest that efficient inhibition of a glycosidase at its pH optimum by an appropriate iminoalditol will be found when the pKa of the iminoalditol is below that of the acid-catalytic group of the target enzyme. PMID- 2310376 TI - Calmodulin dependence of transferrin receptor recycling in rat reticulocytes. AB - Kinetic analysis of transferrin receptor properties in 6-8 day rat reticulocytes showed the existence of a single class of high-affinity receptors (Kd 3-10 nM), of which 20-25% were located at the cell surface and the remainder within an intracellular pool. Total transferrin receptor cycling time was 3.9 min. These studies examined the effects of various inhibitors on receptor-mediated transferrin iron delivery in order to define critical steps and events necessary to maintain the functional integrity of the pathway. Dansylcadaverine inhibited iron uptake by blocking exocytic release of transferrin and return of receptors to the cell surface, but did not affect transferrin endocytosis; this action served to deplete the surface pool of transferrin receptors, leading to shutdown of iron uptake. Calmidazolium and other putative calmodulin antagonists exerted an identical action on iron uptake and receptor recycling. The inhibitory effects of these agents on receptor recycling were overcome by the timely addition of Ca2+/ionomycin. From correlative analyses of the effects of these and other inhibitors, it was concluded that: (1) dansylcadaverine and calmodulin antagonists inhibit iron uptake by suppression of receptor recycling and exocytic transferrin release, (2) protein kinase C, transglutaminase, protein synthesis and release of transferrin-bound iron are not necessary for the functional integrity of the iron delivery pathway, (3) exocytic transferrin release and concomitant receptor recycling in rat reticulocytes is dependent upon Ca2+/calmodulin, (4) dansylcadaverine, dimethyldansylcadaverine and calmidazolium act on iron uptake by interfering with calmodulin function, and (5) the endocytotic and exocytotic arms of the iron delivery pathway are under separate regulatory control. PMID- 2310377 TI - Purification and characterization of heparin-binding growth factors from porcine uterus. AB - Heparin-binding growth factors present in pig uterine tissue were purified by approx. 50,000-fold using a combination of ammonium sulphate precipitation, ion exchange chromatography and heparin-affinity chromatography. Purification of the uterus-derived growth factors (UDGFs) was monitored by the stimulation of [3H]thymidine incorporation into Swiss 3T3 cells and by a radioreceptor assay using 125I-labelled epidermal growth factor (EGF) as the ligand. The latter was shown to be a novel, rapid and reliable assay for heparin-binding growth factors which utilizes their trans-modulation of EGF receptor affinity. UDGFs exhibit strong affinity for immobilized heparin and two forms, named alpha UDGF and beta UDGF, were distinguished by salt gradient elution from heparin-agarose affinity columns. beta UDGF activity was eluted from heparin-agarose between 1.5 M- and 1.8 M-NaCl, and was correlated with the elution of a protein doublet of 17.2 kDa and 17.7 kDa. Immunoblotting of heparin-purified beta UDGF indicated that the beta UDGF doublet is immunologically related to the 146-amino-acid form of bovine basic fibroblast growth factor (bFGF), and that the 17.2 kDa component is an N terminally truncated form of the 17.7 kDa component. After purification by C4 reversed-phase h.p.l.c., this doublet was biologically active and greater than 95% pure as assessed by silver-stained SDS/PAGE. Amino acid composition and sequence analysis confirmed that these beta UDGF polypeptides were microheterogeneous forms of bFGF. Fractions containing alpha UDGF activity were eluted from heparin-agarose in 1.3 M-NaCl. These fractions contained a 16.5 kDa protein which co-migrated on SDS/polyacrylamide gels with recombinant human acidic FGF (aFGF) and which which cross-reacted with an antiserum raised against aFGF. The identification of heparin-binding growth factors in porcine uterus at the time of implantation raises the possibility that they function in the reproductive tract during early pregnancy. PMID- 2310379 TI - Inactivation of pyruvate decarboxylase by 3-hydroxypyruvate. AB - Pyruvate decarboxylase from Zymomonas mobilis is inhibited by 3-hydroxypyruvate, which can also act as a poor substrate. While catalysing the decarboxylation of this alternative substrate, the enzyme undergoes a progressive but partial inactivation over several hours. The extent of inactivation depends upon the pH and upon the concentration of 3-hydroxypyruvate. After partial inactivation and removal of unchanged 3-hydroxypyruvate, enzymic activity recovers slowly. We suggest that inactivation results from accumulation of enzyme-bound glycollaldehyde, which is relatively stable, possibly because it is dehydrated to form an acetyl group. PMID- 2310378 TI - Mouse C-reactive protein. Generation of cDNA clones, structural analysis, and induction of mRNA during inflammation. AB - A full-length C-reactive protein (CRP) cDNA clone has been isolated from a CBA/J strain-mouse acute-phase liver library. The 1614-nucleotide cDNA specifies mRNA 5' and 3' untranslated regions of 81 and 858 bases respectively that flank 675 bases encoding mouse pre-CRP. The derived amino acid sequence predicts a 19 residue leader peptide followed by a 206-residue mature mouse CRP that shows considerable sequence identity with both human and rabbit CRP. Northern-blot analysis of mouse liver CRP mRNA concentrations after inflammatory stimuli and comparison with hepatic induction of mRNA for the major mouse acute-phase protein serum amyloid P component established that CRP, a major acute-phase reactant in human and rabbit, is a minor acute-phase reactant in mouse. The size and organization of the mouse CRP mRNA 5' and 3' untranslated regions are significantly different from those of human and rabbit CRP mRNA and may have implications for its anomalous minimal induction during acute inflammation. PMID- 2310380 TI - Vesicles with lactate dehydrogenase and without alkaline phosphatase present in the resting zone of epiphyseal cartilage. AB - Matrix vesicles are membrane-invested vesicles that initiate mineralization in the extracellular matrix of calcifying tissues. The epiphyseal cartilages of young-rat rib bones were divided into the growth zone and the resting zone, followed by the isolation of matrix vesicles after collagenase treatment. Matrix vesicles with both alkaline phosphatase and lactate dehydrogenase were detected in the growth cartilage found in the epiphyseal growth plates of young rabbits [Hosokawa, Uchida, Fujiwara & Noguchi (1988) J. Biol. Chem. 263, 10045-10047], but were not detected in the resting zone. By contrast, and surprisingly, lactate dehydrogenase-containing vesicles without alkaline phosphatase were found in the resting zone, but not in the growth zone. In both the growth and resting zones, isoenzyme patterns of lactate dehydrogenase in the two different vesicles were identical with those of cytosolic lactate dehydrogenase of chondrocytes, suggesting the presence of a mechanism for specific uptake of cytosolic lactate dehydrogenase. The same results as for young-rat rib bones were obtained with the resting and growth cartilages of young-dog and monkey rib bones. PMID- 2310383 TI - Quantitative analysis of human immunodeficiency virus type-1 DNA in asymptomatic carriers using the polymerase chain reaction. AB - A method for detecting human immunodeficiency virus type 1 (HIV-1) provirus DNA in lymphocytes with improved sensitivity and reproducibility was developed using the polymerase chain reaction (PCR). Amplified HIV-1 DNA was hybridized with a 32P-labeled probe and quantitated with a beta-scanner after electrophoresis. A linear relationship was obtained between the common logarithms of the counts detected and the number of HIV-1 DNA copies applied to the PCR. Detectability was from 3 copies/10(5) lymphocytes, and linearity was maintained from 10 to 10(3) copies. HIV-1 DNA was detected in all 9 asymptomatic carriers tested (18 to 2,857 copies/10(5) CD4+ T lymphocytes). The viral burden was inversely related to the CD4+ lymphocyte count, suggesting that quantitation of provirus levels may serve as a predictor of progress in early HIV infection. PMID- 2310381 TI - Theoretical approach to the steady-state kinetics of a bi-substrate acyl-transfer enzyme reaction that follows a hydrolysable-acyl-enzyme-based mechanism. Application to the study of lysophosphatidylcholine:lysophosphatidylcholine acyltransferase from rabbit lung. AB - A kinetic model is proposed for catalysis by an enzyme that has several special characteristics: (i) it catalyses an acyl-transfer bi-substrate reaction between two identical molecules of substrate, (ii) the substrate is an amphiphilic molecule that can be present in two physical forms, namely monomers and micelles, and (iii) the reaction progresses through an acyl-enzyme-based mechanism and the covalent intermediate can react also with water to yield a secondary hydrolytic reaction. The theoretical kinetic equations for both reactions were deduced according to steady-state assumptions and the theoretical plots were predicted. The experimental kinetics of lysophosphatidylcholine:lysophosphatidylcholine acyltransferase from rabbit lung fitted the proposed equations with great accuracy. Also, kinetics of inhibition by products behaved as expected. It was concluded that the competition between two nucleophiles for the covalent acyl enzyme intermediate, and not a different enzyme action depending on the physical state of the substrate, is responsible for the differences in kinetic pattern for the two activities of the enzyme. This conclusion, together with the fact that the kinetic equation for the transacylation is quadratic, generates a 'hysteretic' pattern that can provide the basis of self-regulatory properties for enzymes to which this model could be applied. PMID- 2310382 TI - Cathepsin G binding to human platelets. Evidence for a specific receptor. AB - We have shown previously that purified human neutrophil cathepsin G is a strong platelet agonist. We now demonstrate that cathepsin G exhibits saturable, reversible binding to human platelets which is characteristic of binding to a specific receptor. At room temperature, cathepsin G displayed apparent positive co-operativity of binding, as indicated by sigmoidal binding curves and a Hill coefficient greater than unity. By contrast, binding curves conducted with native enzyme at 0.5 degrees C displayed a much smaller degree of sigmoidicity, and binding studies performed with phenylmethanesulphonyl fluoride-treated enzyme at 22-25 degrees C exhibited hyperbolic binding curves. The concentrations of cathepsin G required to give half-saturation (S0.5) with inhibitor-treated enzyme or with native enzyme at either room temperature or 0.5 degrees C were all similar, suggesting that sigmoidal binding curves did not result from an alteration in the affinity of the binding sites for cathepsin G. However, platelets bound approximately twice as many molecules of native enzyme as molecules of phenylmethanesulphonyl fluoride-treated cathepsin G per cell. From these observations it can be inferred that the apparent positive co-operativity may in part reflect the exposure of binding sites due to the proteolytic activity of cathepsin G. However, this conclusion is not supported by experiments conducted with subsaturating cathepsin G concentrations, which demonstrated that ligand binding did not show an expected increase at longer time intervals. Measurement of Ca2+ mobilization and cathepsin G binding in the same platelet suspensions demonstrated that elevations in cytosolic free Ca2+ concentration had achieved near-maximal levels in the presence of 15 micrograms of cathepsin G/ml, whereas maximal binding was observed at approx. 35 micrograms/ml, indicating that only a fraction of the total binding sites need be occupied to elicit platelet activation. Pretreatment of platelets with forskolin or phorbol 12-myristate 13 acetate (PMA) decreased cathepsin G binding by approx. 60% and 40% respectively, indicating that the receptor may be desensitized or down-regulated by phosphorylation due to protein kinases. Since forskolin and PMA could diminish receptor availability by activating negative feedback mechanisms, inhibition of negative signal-transduction pathways could conversely play a role in the up regulation of cathepsin G binding. In any event, these results show that cathepsin G is an agonist that must bind to platelets to initiate processes associated with cell activation, and suggest a role for cathepsin G in platelet function. PMID- 2310384 TI - Simulation of the inhibitory cystatin surface by a synthetic peptide. AB - An inhibitory dodecameric peptide was designed which tentatively mimics the inhibitory site of cystatin C-like structures. Succinylated and mansylated derivatives were also synthesised and assayed for their inhibiting properties towards papain and rat cathepsins B, H and L. All peptides preferentially inhibit cathepsin L and papain as their naturally occurring inhibitor model. A significant increase in inhibition was obtained after mansylation of the crude peptide with Ki values in the micromolar or 0.1 micromolar range. The use and interest of such peptide inhibitors are discussed. PMID- 2310385 TI - 14, 15-Epoxyeicosatrienoic acid promotes endothelial cell dependent adhesion of human monocytic tumor U937 cells. AB - Arachidonic acid (AA) can be metabolized in endothelial cells (EC) to a series of epoxides via cytochrome P-450 epoxygenase with 14,15 epoxyeicosatrienoic acid (14,15-EET) as the major product. In this communication we report that 14,15-EET significantly enhances U937 cell attachment to EC with maximal cell attachment at 2.5 to 5 x 10(-7) M 14,15-EET. Thus, 14,15-EET may play a substantial role in inflammation and/or atherogenesis by inducing monocyte attachment to EC. PMID- 2310386 TI - Control of mitochondrial matrix calcium: studies using fluo-3 as a fluorescent calcium indicator. AB - Fluo-3, a fluorescent Ca2+ indicator, is sequestered by isolated rat liver mitochondria and is an effective probe for evaluating the concentration and kinetics of change of mitochondrial matrix ionized calcium ([Ca2+]m) under a variety of conditions. At the wavelengths employed, there is no significant interference by auto-fluorescence. There is an insignificant release of the indicator over four hours and the loading and presence of fluo-3 has no effect on respiratory rate or oxidative phosphorylation. The [Ca2+]m steady state can be altered by the assay conditions, i.e. the presence of extra-mitochondrial Ca2+, Mg2+ phosphate and respiratory inhibitors. The total matrix ionized calcium represents a small percent (less than 0.01%) of the total mitochondrial calcium. PMID- 2310387 TI - The amino-terminal sequence of lobster fibrinogen reveals common ancestry with vitellogenins. AB - The amino-terminal sequence of lobster "fibrinogen" was determined. A computer search of the sequence revealed that the lobster protein is homologous to vitellogenins (precursors of egg-yolk proteins). PMID- 2310388 TI - Identification of a region of calsequestrin that binds to the junctional face membrane of sarcoplasmic reticulum. AB - The interaction of calsequestrin (CSQ) with the channel-containing region of the sarcoplasmic reticulum (junctional face membrane, jfm) is involved in Ca2+ release, and it seemed of interest to identify the jfm-binding region of the CSQ molecule. For this purpose, CSQ was digested with trypsin, and peptides were screened for jfm binding. Partial amino acid sequencing of selected peptides allowed us to localize a critical site for jfm binding in the stretch encompassing residues 86-191. PMID- 2310389 TI - Effects of ethidium bromide treatment of mouse cells on expression and assembly of nuclear-coded subunits of complexes involved in the oxidative phosphorylation. AB - Using mouse cell lines 5P and 5PEr (ethidium bromide-resistant derivative of 5P), we examined the influence of blocking expression of mitochondrial-gene products with ethidium bromide on the expression and assemblies of nuclear-coded subunits of the complexes involved in the oxidative phosphorylation. The results suggest that in the absence of mitochondrial-coded products, the expressions of subunit VIc of complex IV and beta-subunit of F1-ATPase are not affected, but that most nuclear-coded subunits other than alpha- and beta-subunits of F1-ATPase cannot be assembled nor inserted into the inner membrane. PMID- 2310390 TI - Virosomes reconstituted from human immunodeficiency virus proteins and lipids. AB - Purified Human Immunodeficiency Virus (HIV) was solubilized in octylglucopyranoside. After centrifugation, the supernatant was added to lipid detergent mixed micelles. Formation of virosomes occurred during overnight dialysis. Centrifugation on a continuous glycerol gradient showed that envelope glycoproteins (gp120 and gp41) and matrix protein p17 but not core protein p25 were associated to virosomes. Proteolytic treatment of virosomes indicates that gp120 is oriented toward the outside as in the virus particles, whereas p17 protein is anchored on both sides of the liposomal membrane. Virosomes are spherical vesicles with approximately the size of the virus as shown by electron microscopy. PMID- 2310391 TI - Increase in calcitonin mRNA levels in rats at high risk of C cell tumours is genetically determined. AB - C-cells tumours are frequent (50%) in old WAG/Rij rats. In comparison to the original Wistar strain, three month old WAG/Rij rats are characterized by higher calcitonin synthesis and secretion, in addition to a genetically transmitted loss of calcitonin binding sites in the outer renal medulla. In order to determine if the increase of calcitonin gene expression is also of genetic origin, we quantified calcitonin and its specific messenger in the thyroid glands of second generation (Wistar x WAG/Rij) hybrids. These parameters ranged from low Wistar like to higher WAG/Rij like values. The amount of calcitonin messenger in the thyroid was highly correlated to the release of the hormone in plasma elicited by a calcium challenge and inversely correlated with the number of its binding sites in the kidney. Our results suggest that an enhanced expression of the calcitonin gene is genetically transmitted, probably as a consequence of the mutation involved in the loss of renal calcitonin binding sites. It may represent the first event leading to malignancy. PMID- 2310392 TI - Purification and characterization of a liposomal-forming tetraether lipid fraction. AB - Polar lipid E, PLE, a native tetraether lipid mixture from Sulfolobus acidocaldarius is shown to spontaneously form multilamellar liposomes in aqueous media. PLE lipids were isolated as a single fraction from the crude lipid extract of S. acidocaldarius on a reverse-phase column followed by TLC and methanol precipitation. The methanol-precipitated mixture was able to form liposomes, whereas the non-precipitated material did not. It has thus been demonstrated, for the first time, that tetraether lipids from S. acidocaldarius can form liposomes, per se, in aqueous media. PMID- 2310393 TI - Latent form of transforming growth factor-beta 1 acts as a potent growth inhibitor on a human erythroleukemia cell line. AB - Recombinant latent form of transforming growth factor-beta 1 (L-TGF-beta 1) is activated by various chemical treatments, including acidification and heating. However, cellular mechanisms that release transforming growth factor-beta (TGF beta) in an active form have not been fully elucidated. Investigated herein are the effects of L-TGF-beta 1 on various leukemic cell lines. Heat-activated L-TGF beta 1 inhibited colony formation of U937, KG-1 and HL-60, whereas untreated L TGF-beta 1 had only a marginal effect on these cells. In contrast, colony formation of human erythroleukemia cell line (HEL) was markedly inhibited by both heat-activated and untreated L-TGF-beta 1. In vitro incubation of L-TGF-beta 1 with HEL cells did not release the active form in the culture supernatants. These results suggest that HEL cells are capable of activating L-TGF-beta 1, but only in a cell-associated manner. Since HEL cells produce L-TGF-beta 1, it may act as an autocrine negative growth factor on these cells. PMID- 2310394 TI - A molluscan neuropeptide related to the crustacean hormone, RPCH. AB - A peptide that potentiates twitch contraction of the radula retractor muscle of the prosobranch mollusc Fusinus ferrugineus was isolated from the ganglia of the animal. Its primary structure is H-Ala-Pro-Gly-Trp-NH2 (APGWamide) closely related to the C-terminal tetrapeptide of the crustacean red-pigment concentrating hormone. APGWamide showed modulatory actions on contractions in various molluscan muscles. PMID- 2310395 TI - Involvement of Ca2(+)-induced Ca2+ release in the volume regulation of human epithelial cells exposed to a hypotonic medium. AB - Exposure of cultured human epithelial cells (Intestine 407) to a hypotonic solution results in initial osmotic swelling and in a subsequent volume decrease near to the original level. The regulatory volume decrease was inhibited by reduction of the extracellular free Ca2+ concentration to 90 nM. Single epithelial cells responded to a hypotonic challenge with a biphasic increase in the cytosolic free Ca2+ level from about 90 to 200 nM. Both phases of the Ca2+ rise were abolished by reducing the extracellular Ca2+ to 90 nM. In the presence of caffeine (20 mM), the second-phase Ca2+ response to a hypotonic challenge occurred earlier immediately after the first-phase response. The second-phase Ca2+ response was selectively impaired by adenine (10 mM), procaine (1 mM) or ryanodine (5 to 10 microM). These blockers for Ca2(+)-induced Ca2+ release channels inhibited volume regulation after osmotic swelling. It is concluded that Ca2(+)-induced Ca2+ release from a ryanodine-sensitive store is a prerequisite for the volume regulation of human intestinal epithelial cells under hypotonic conditions. PMID- 2310396 TI - The two mRNA forms for the type I alpha regulatory subunit of cAMP-dependent protein kinase from human testis are due to the use of different polyadenylation site signals. AB - Using a cDNA probe for the type I alpha regulatory subunit, two mRNA species (1.5 and 3.0 kb in length) were detected in human testis. From a human testis cDNA library a 3.0 kb clone, containing the entire reading frame of the protein, was isolated. Comparison of the nucleotide sequence of this clone to the sequence of a 1.5 kb cDNA clone earlier reported, showed that the longer clone was identical to the shorter but extended another 1.5 kb in the 3' end. Sequencing data together with Northern blot analysis indicated that the two mRNA species for human type I alpha regulatory subunit were generated from the same gene by the use of different polyadenylation site signals. PMID- 2310397 TI - Specific inactivation of glutathione S-transferases in class Pi by SH-modifiers. AB - Treatment of Class Pi glutathione S-transferases (GST) such as rat GST P (7-7), human GST pi and mouse GST MII with 0.05-0.1 mM N-ethylmaleimide (NEM) in 0.1 M Tris-HCl (pH 7.8) resulted in almost complete inactivation of these forms, whereas no or less inactivation occurred for GSTs in Class Alpha and Mu under the same conditions. Inactivated GST P lost its S-hexyl-GSH-Sepharose column affinity. About 0.8 mol of [14C]NEM was found to be covalently bound to 1 mol of GST P subunit when 80% of the activity was lost. Similar treatment with N dimethyl-amino-3,5-dinitrophenyl maleimide, a colored analogue of NEM, followed by trypsin digestion, HPLC and amino acid sequence analysis revealed that one cysteine residue at the 47th position from the N-terminal of the GST P subunit was preferentially modified. Subunits of GST P and GST pi are known to have 4 cysteine residues at the same corresponding positions. The present results suggest that the 47th cysteine residue may be located in the vicinity of the active site of Class Pi GSTs. PMID- 2310398 TI - Low-density lipoprotein elevates intracellular calcium and pH in vascular smooth muscle cells and fibroblasts without mediation of LDL receptor. AB - Low-density lipoprotein (7 micrograms/ml) induced in the absence or in the presence of 7, 35, 70 micrograms/ml monoclonal antibodies against the specific Low-density lipoprotein receptor an elevation of intracellular Ca2+ from 105 to approximately 210 nM in vascular smooth muscle cells from rat aorta. Moreover, in both human cultured fibroblasts from normocholesterolemic individuals and from patients with familial hypercholesterolemia homozygote class 1, Low-density lipoprotein (7 micrograms/ml) induced a rise of free intracellular calcium and a biphasic change of intracellular pH. Low-density lipoprotein (1,7,15,30 micrograms/ml) had no significant influence on the phosphatidylinositol-turnover in vascular smooth muscle cells and fibroblasts. Since homozygote class 1 fibroblasts lack specific Low-density lipoprotein receptors, and as antibodies against this receptor did not attenuate the Low-density lipoprotein-induced elevation of cytosolic calcium and pH, we conclude that these intracellular changes are independent from the classical Low-density lipoprotein receptor. PMID- 2310399 TI - Transport of glutathione across the mitochondrial membranes. AB - Transport of glutathione (GSH) into mitochondria was observed when mitochondria in state 4 respiration were incubated with high concentrations of GSH. This transport was suppressed by antimycin A or dicyclohexyl-carbodiimide, or in state 3 respiration. Upon dissipation of the proton gradient by a proton ionophore, mitochondrial GSH was released into the medium. GSH moved freely across the proton-permeated mitochondrial membrane, its movement depending only on the GSH gradient across the inner membrane. These results indicate that there is a transport system for GSH in the mitochondrial membrane, and that a proton gradient is necessary to maintain GSH in the matrix, and to transport GSH into mitochondria. PMID- 2310400 TI - Isovalerylcarnitine is a specific activator of the high calcium requiring calpain forms. AB - Isovalerylcarnitine, a product of the catabolism of L-leucine, is a potent activator of rat calpains isolated from erythrocytes, kidney, liver, skeletal and heart muscle. Only calpains II, but not calpains I, are activated by IVC, with the only exception of rat erythrocyte calpain I, the only species present in these cells which has a Ca2+ requirement higher than that of most calpain I isoenzymes. Activation by IVC involves a dual effect: 1) a ten fold increase in the affinity of calpain for Ca2+, and 2) an increase in the Vmax 1.3-1.6 fold above the values observed with the native enzymes at saturating [Ca2+] as well as with the autolyzed fully active calpain form at 5 microM Ca2+. The increased affinity for calcium results in an increased rate of autoproteolysis of calpain II. Activation by IVC is additive to that promoted by interaction (or association) to phospholipids vesicles. Together these results suggest that IVC may operate as a selective activator of calpain both in the cytosol and at the membrane level; in the latter case in synergism with the activation induced by association of the proteinase to the cell membrane. PMID- 2310401 TI - Research on the mechanism of interaction between actin and membrane lipids. AB - Using an in vitro system involving pure actin and liposomes, we have established that actin may interact with membrane lipids without any intermediate proteins, and that the mechanism of interaction depends upon the concentration of divalent cation. In the absence of divalent cation, actin increases membrane permeability. Low concentrations (1 mM) of divalent cation potentialize this interaction. In the presence of high divalent cation concentration, actin deposits on the surface of liposomes in a crystalline organization and reduces the membrane microviscosity as shown by the polarization of fluorescence of the DPH probe. We propose that actin interacts with lipids by hydrophobic association which is facilitated by initial electrostatic binding. PMID- 2310402 TI - Fast kinetic analysis of drug transport in multidrug resistant cells using a pulsed quench-flow apparatus. AB - One major feature of multidrug resistance is the reduced cellular level of drugs maintained by MDR cells. Although there is now strong evidence that drugs are actively pumped out of MDR cells, transport experiments have indicated decreased initial rates of influx at the earliest times at which measurements could be made. We have used a pulsed quench-flow apparatus to study transport characteristics of colchicine resistant MDR cells on a very fast time scale. A rapid association of daunomycin with drug sensitive cells occurred within 0.11 sec. This association is virtually absent in MDR cells. In efflux experiments performed on the same rapid time scale, greater than 50% of daunomycin efflux occurred within 0.1 sec. No substantial efflux from B1, drug sensitive cells was observed. On the other hand, vinblastine accumulation by both cell types was similar for approx. 10 seconds. Thus, kinetically, not all drugs are handled in a similar fashion by MDR cells. The pulsed quench-flow apparatus was useful in making fast time measurements of drug influx and efflux and in demonstrating the differences between drug recognition patterns by MDR cells. PMID- 2310403 TI - Hepatocytes mediate coenzyme A transfer to specific carbohydrate-derivatized surfaces. AB - Freshly isolated chicken and rat hepatocytes adhere with carbohydrate specificity to surfaces derivatized with N-acetylglucosamine and galactose respectively. Previously (Brandley, B.K. and Schnaar, R.L. (1985) J. Biol. Chem. 260, 12474 12483) we reported that metabolically radiolabeled chicken hepatocytes covalently transferred phosphate radiolabel specifically to N-acetylglucosamine-derivatized surfaces. We now report that rat hepatocytes transfer phosphate radiolabel specifically to galactose-derivatized surfaces. Transferred radiolabel from both species to their appropriate carbohydrate-derivatized surface was identified as CoASH. After specific adhesion via the appropriate carbohydrate, CoASH is apparently released from cells and undergoes disulfide exchange with the cleavable immobilization linker we used to tether the sugars to the artificial surfaces. Although CoASH from lysed cells can undergo similar disulfide exchange, the data suggest that other, perhaps physiological mechanisms may be responsible for the carbohydrate-specific radiolabel transfer. PMID- 2310404 TI - Non-specific interaction of proteoglycans with surfaces and matrices. AB - Evidence is presented that reversible non-specific adsorption of proteoglycans (PGs) to surfaces and matrices is an inherent property of the PGs. This adsorption is dependent on the intact PG structure as the glycosaminoglycans (GAGs), which are isolated after papain digestion of the PG show no such non specific adsorption. The interaction of the PG with surfaces and matrices is also highly dependent on the internal milieu and can be both inhibited and enhanced by such factors as the ionic composition and concentration, pH, detergents and chaotropic reagents such as guanidine hydrochloride (Gdn-HC1). It is suggested that this inherent stickiness of the PGs allows them to function like a reversible fluid adhesant in the connective tissues. This weak binding force thus not only aids in maintaining the integrity of the connective tissues, but its reversible nature may provide for easy movement of other materials through the connective tissue matrix. PMID- 2310405 TI - Isolation, preliminary chemical characterization, and biological activity of Borrelia burgdorferi peptidoglycan. AB - Peptidoglycan (PG), an essential cell wall polymer of most bacteria, has been isolated from many species of spirochetes. Our interest in the host response to Borrelia burgdorferi led us to isolate and characterize its PG. Extracted cells were solubilized with warm 1% SDS followed by digestion with proteases. Amino acid analysis of the isolated PG demonstrated the presence of alanine, glycine, glutamic acid, and ornithine as occurs in other spirochetes and bacteria. Intense erythematous reactions were observed after id injection of 10 micrograms of PG into normal human skin. PG was not mitogenic for human peripheral blood mononuclear cells. Murine splenocytes of certain strains responded to the PG, but only at concentrations of 25 micrograms/ml or more. PG stimulated macrophages to produce interleukin 1. Sixteen micrograms of PG injected iv into rabbits produced biphasic fevers. These observations on the in vitro and in vivo activities associated with the cellular components of the B. burgdorferi spirochete give further insight to how a small number of invading organisms can cause a multisystemic disease such as Lyme disease. PMID- 2310406 TI - Enzyme coupling method on calibrated nylon spheres: application to the selective trypsinization of histones in chromatin. AB - A new method consisting of a two-step activation was developed in order to covalently immobilize enzymes on calibrate nylon 66 spheres. This efficient method associates for the first time peptide bond cleavage and O-alkylation of the support. Optimal conditions for activation and protein coupling were defined, and immobilized trypsin was used to investigate the histone accessibility on chromatin. This approach, which allows us to degrade first progressively H1, indicates that H4 seems inaccessible both in relaxed and condensed chromatin. PMID- 2310407 TI - Thyroid function and thyroxine metabolism in hexachlorobenzene-induced porphyria. AB - The effects of hexachlorobenzene (HCB) administration on the development of porphyria and on changes in thyroid function and thyroid hormone metabolism were examined. Female Wistar rats were treated with HCB for 1 or 8 weeks. At both treatment times liver weight was notably increased with a slight change in thyroid weight at 8 weeks. Serum thyroxine (T4) levels were depressed, whereas levels of triiodothyronine (T3) were not depressed significantly at both treatment times. One or eight weeks of HCB treatment did not alter the incorporation and distribution of [125I] into intrathyroidal aminoacids. A 50% reduction in protein bound iodine (PB[125I]) was seen in both groups of animals. HCB altered [125I]T4 metabolism in rat liver slices, increasing T4 dehalogenation. HCB administration for 1 week did not affect urinary excretion of porphyrins or their precursors, or hepatic porphyrin content. The activity of aminolaevulinate synthase was not affected, but there was a 25% and 51% inhibition in porphyrinogen carboxy-lyase (PCL) activity for the uroporphyrinogen disappearance or the coproporphyrinogen formation respectively. After 8 weeks of HCB administration the rats showed a characteristic porphyria. Our results show that HCB treatment increased hepatic thyroxine metabolism, without alterations in thyroid hormone synthesis. Serum T4 and PCL activity behaved differently in both time- and dose-dependent studies, with serum T4 being the more sensitive parameter which responded at earlier times and lower doses. PMID- 2310408 TI - The inhibition of glutamate dehydrogenase by some antipsychotic drugs. AB - The phenothiazines chlorpromazine and perphenazine and the butyrophenone haloperidol were shown to be reversible inhibitors of glutamate dehydrogenase (GDH). Inhibition by chlorpromazine was found to be partial, whereas haloperidol and perphenazine would, apparently, give full inhibition at saturating concentrations. Double-reciprocal plots of the difference between activities in the absence and presence of the inhibitor against the inhibitor concentration were linear with chlorpromazine and perphenazine but parabolic when haloperidol was used as the inhibitor. Comparisons between the responses of commercially available preparations of ox liver GDH, which have been shown to have suffered limited proteolysis during purification, and the ox brain enzyme prepared by a procedure which does not result in such proteolysis, revealed the latter preparation to be more sensitive to inhibition because of a higher apparent affinity for these drugs. The apparent dissociation constants for enzyme-drug interactions were, however considerably higher than the concentrations that have been reported to occur in vivo following chronic administration of chlorpromazine and haloperidol. This casts doubt on earlier claims that inhibition of GDH may be involved in the antipsychotic actions of these drugs, although it might be a factor in the side effects associated with the use of such compounds. PMID- 2310409 TI - Biochemical mechanism of metallothionein--carbon tetrachloride interaction in vitro. AB - To elucidate the mechanism underlying the protective effect of metallothionein (MT) against carbon tetrachloride (CCl4) toxicity, in vitro experiments were carried out to study the interaction of metallothionein and CCl4. Results from this study showed that incubation of Cd,Zn-MT with CCl4 in the presence of hepatic microsomes and NADPH resulted in a time-dependent depletion of MT thiols with a concurrent reduction in the metal-binding sites of the protein. Moreover, this reaction also released Zn and Cd from MT. Results from experiments conducted to determine whether or not the CCl4-induced decrease in MT-thiol content was due to the scavenging of CCl4 metabolite(s) showed that the trichloromethyl radical, chloroform and phosgene as well as the products of CCl4-induced microsomal lipid peroxidation were not directly involved. Although covalent binding of 14CCl4 to MT was detected following incubation in the presence of a microsomal bioactivation system, it did not account for the CCl4-induced loss of MT thiol groups for the following reasons: (i) prior oxidation of sulfhydryl groups of MT by hydrogen peroxide did not alter the binding; and (ii) anaerobiosis did not alter the extent of covalent binding but obliterated the inhibitory effect of CCl4 on MT thiol content. Measurement of the thiol content of CCl4-treated MT after treatment with 1,4-dithiothreitol revealed that all the thiol groups that were lost subsequent to CCl4 treatment could be regenerated. These data suggest that CCl4-linked oxidation of MT, rather than the covalent binding of 14CCl4 metabolite(s), may be responsible for the CCl4-induced loss of metal binding sites of MT with the concurrent release of Zn and Cd. However, the precise role of the metal released during the oxidation of MT in CCl4 toxicity remains to be defined. PMID- 2310410 TI - Diethylcarbamazine, antifilarial drug, inhibits microtubule polymerization and disrupts preformed microtubules. AB - The effect of diethylcarbamazine (DEC) on microtubules was studied by using microtubule protein prepared from porcine brain. DEC inhibited assembly of microtubules and disassembled preformed microtubules in vitro. When the reassembled or disassembled products were examined in the presence of DEC by electron microscopy, ribbon-microtubules were frequently observed. Subsequently, the effect of DEC on the cytoplasmic microtubules complex was studied. The cells used in our study were LLC-MK2. DEC inhibited proliferation of these cells, and cells grown in the presence of DEC were likely to separate from each other and became round in shape. Immunofluorescence microscopy revealed that the cells exposed to DEC were devoid of the delicate pattern of the cytoplasmic microtubule complex. PMID- 2310411 TI - In vitro translational activity of messenger-RNA isolated from mice treated with the interferon inducer, polyriboinosinic acid.polyribocytidylic acid. AB - Treatment of mice with interferon and interferon inducers causes down regulation of a number of hepatic proteins. In a previous publication it was demonstrated that these treatments depress hepatic protein synthesis and increase protein degradation, particularly of the endoplasmic reticulum Gooderham NJ and Mannering GJ, Arch Biochem Biophys 250: 418-425, 1986. In the present study the effects of polyriboinosinic acid.polyribocytidylic acid (poly IC) treatment on mouse hepatic RNA levels and the translation of this RNA in a cell-free system were examined. Poly IC treatment of mice increased hepatic poly (A+) RNA levels. The translation of isolated poly(A+)RNA was evaluated at various intervals after the administration of poly IC. Translation was marginally increased at 3-6 hr after treatment and depressed after 12-18 hr. Antibodies were employed to examine the effects of poly IC treatment on specific polypeptides in order to evaluate the in vitro translation of mRNAs for tyrosine aminotransferase and albumin; translation of these proteins was biphasic with pronounced depression. These studies indicate that in vivo interferon may regulate gene expression by altering levels of hepatic proteins via increased transcription and decreased translation. PMID- 2310412 TI - Differences in the kinetic properties and sensitivity to inhibitors of human placental, erythrocyte, and major hepatic aldehyde dehydrogenase isoenzymes. AB - (i) The characteristics of the major human hepatic isoenzymes of aldehyde dehydrogenase (ALDH), ALDH I and ALDH II, were compared with the ALDH activities found in human placenta and erythrocytes, (ii) In human liver biopsies, the Km of ALDH I was approximately 7 mumol/L whereas it was 32 mumol/L for ALDH II. The Vmax for ALDH I was 2-3 times greater than the ALDH II Vmax. Human liver ALDH I and II also differed in their sensitivity in inhibitors. Namely, ALDH I was less sensitive to disulfiram than the ALDH II isoenzyme. (iii) ALDH activity in human placenta and erythrocytes was much lower than in liver tissue. Kinetic data showed that placental ALDH isoenzyme had a high Km (in the millimolar range) and increased its activity raising the pH from 7.4 to 8.8, more than the hepatic ALDH I and ALDH II isoenzymes did. Erythrocyte ALDH activity presented a dual component; the smaller one was characterized by a low Km (micromolar range), whereas most of the ALDH activity showed a high Km (millimolar range). (iv) Placental ALDH was resistant to nitrefazole inhibition and was inhibited by disulfiram in a manner similar to the hepatic ALDH I isoenzyme; erythrocyte ALDH was more sensitive to the inhibitory action of disulfiram and nitrefazole. (v) It is concluded that erythrocyte and placental ALDH isoenzymes are different from the hepatic ALDH I and ALDH II forms. It is also suggested that placental and erythrocyte ALDH isoenzymes are different high-Km isoenzymes. PMID- 2310413 TI - Activation of calcium uptake in rat liver mitochondria by aminoglucoside antibiotics. AB - Ca uptake in rat liver mitochondria is accelerated by various aminoglucoside antibiotics and, to a lesser degree, by triethylenetetramine and by protamine. With 1 mM Mg2+ and at a concentration of Ca2+ = 2 microM maximal (about six-fold) activation is achieved with 20 microM neomycin; at higher concentrations of the antibiotic the velocity of Ca uptake decreases. Activation to the same degree by gentamicin, kanamycin or streptomycin requires higher concentrations of the antibiotics. The reason for the acceleration of Ca uptake by neomycin is an allosteric alteration of the kinetics corresponding to that previously observed in the presence of spermine. The conformity with effects of spermine and possible inferences of that conformity are discussed. PMID- 2310414 TI - Comparison of graphical procedures for estimating the intrinsic molar fluorescence of protein-bound drugs for drug-binding studies. A reevaluation of existing plots and introduction of two inverse hyperbolic plots. AB - A theoretical evaluation of existing and new graphical procedures for estimating the intrinsic molar fluorescence (psi B) of a protein-bound drug has been undertaken. The results do not concord with a recent proposition that psi B should be obtained by direct reading from a graph of emitted fluorescence intensity (I) against the logarithm of the binding protein concentration ([P]) rather than by extrapolation of a double reciprocal plot. The calculated errors in estimates of psi B obtained by direct reading or by extrapolation of standard plots and of three new inverse hyperbolic plots showed that, independently of binding affinity: 1. Direct reading from the logarithmic plot gave the least accurate estimates. 2. The single reciprocal plot gave more accurate estimates than the double reciprocal plot providing the (constant) drug concentration was similar to or greater than its dissociation constant in the binding system. At lower drug concentrations the double reciprocal plot gave more accurate estimates. 3. Extrapolation of an inverse hyperbolic sine plot (sinh-1 (1/I) against 1/[P]) did not give more accurate estimates than the standard reciprocal plots. 4. If the drug concentration was close to its dissociation constant the most accurate estimates were obtained with an inverse hyperbolic cosine plot of cosh-1 (I + 1) against 1/[P]. For a low affinity binding system in which non specific binding is significant an inverse hyperbolic sine plot of 1/sinh-1I against 1/[P] gave the most accurate estimates at low drug concentrations. An experimental and theoretical procedure for optimizing the estimation of psi B is proposed on this basis. PMID- 2310415 TI - Purification of a sheep liver cytochrome P-450 from the P450IIIA gene subfamily. Its contribution to the N-dealkylation of veterinary drugs. AB - Oral administration of troleandomycin at a dose of 100 mg/kg/day for 6 days to three adult male Lacaune sheep produced a 1.6-fold increase in specific content of liver microsomal cytochrome P-450. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, microsomal preparations from treated animals exhibited a strong band in the zone of electrophoretic mobility of cytochromes P-450. This band corresponded to a cytochrome P-450 which cross-reacted with rabbit P450IIIA6 antibodies, as demonstrated by immunoblotting. The ovine isozyme was purified to electrophoretic homogeneity by means of successive DEAE cellulose, CM cellulose and hydroxylapatite chromatographic separations. This hemoprotein had an apparent molecular weight of 52 kD as determined by calibrated sodium dodecyl sulfate polyacrylamide gel electrophoresis and was characterized in terms of spectral data, NH2-terminal amino acid sequence, immunologic and catalytic properties. This study revealed some interspecies differences with the orthologous rabbit isozyme. The contribution of this form to the N-demethylation of erythromycin and of three veterinary drugs: chlorpromazine, chlorpheniramine and bromhexine was demonstrated from inhibition by TAO, from immunoinhibition studies, using polyclonal antibodies raised in rabbit and from the existence of significant correlations between its microsomal level and these N-demethylase activities. In contrast, the results suggest that ovine P450IIIA could not be predominantly involved in the N-dealkylation of benzphetamine, ephedrine, ivermectine or spiramycin. PMID- 2310416 TI - Oxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes. AB - Tienilic acid (TA) is metabolized by liver microsomes from phenobarbital-treated rats in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the regioselective hydroxylation of the thiophene ring of TA. During this in vitro metabolism of TA, reactive electrophilic intermediates which bind irreversibly to microsomal proteins are formed. 5 Hydroxylation of TA and activation of TA to reactive metabolites which covalently bind to proteins both required intact microsomes, NADPH and O2 and are inhibited by metyrapone and SKF 525A, indicating that they are dependent on monooxygenases using cytochromes P-450. Microsomal oxidation of an isomer of tienilic acid (TAI) bearing the aroyl substituent on position 3 (instead of 2) of the thiophene ring also leads to reactive intermediates able to bind covalently to microsomal proteins. Covalent binding of TAI, as that of TA, depends on cytochrome P-450 dependent monooxygenases and is almost completely inhibited in the presence of sulfur containing nucleophiles such as glutathione, cysteine or cyteamine. These results show that 5-OHTA, which has been reported as the major metabolite of TA in vivo in humans, is formed by liver microsomes by a cytochrome P-450-dependent reaction. They also show that two thiophene derivatives, TA and TAI, bind to microsomal proteins after in vitro metabolic activation, TAI giving a much higher level of covalent binding than TA (about 5-fold higher) and a much higher covalent binding: stable metabolites ratio (4 instead of 0.5). PMID- 2310417 TI - The kinetic mechanism of inhibition of human leukocyte elastase by MR889, a new cyclic thiolic compound. AB - The cyclic thiolic compound 2-[3-thiophencarboxythio]-N-[dihydro-2(3H) thiophenone-3-il] - propionamide (MR889) was investigated as inhibitor of endopeptidases. The activity of bovine pancreatic alpha-chymotrypsin, human leukocyte cathepsin G and rabbit liver cathepsin B was not affected by MR889, whereas porcine pancreatic elastase and human leukocyte elastase were inhibited. The kinetic mechanism of inhibition of human leukocyte elastase was of the reversible, slow-binding, fully competitive type. The rate constants for complex formation between MR889 and leukocyte elastase, determined by pre-steady-state kinetic analysis in the presence of a tetrapeptide substrate at 37 degrees and pH 7.40, were kon = 2363 +/- 15 M-1 sec-1, koff = 3.01 +/- 0.34 x 10(-3) sec-1. The inhibition equilibrium constant was Ki = koff/kon = 1.27 +/- 0.15 microM. Ki, calculated from steady-state kinetic experiments, was 1.38 microM. MR889 also inhibited the elastolytic activity of leukocyte elastase, as determined with insoluble elastin as the substrate. PMID- 2310418 TI - Hepatic microsomal N-hydroxylation of adenine to 6-N-hydroxylaminopurine. AB - The enzymatic N-hydroxylation of the purine base adenine to the genotoxic and mutagenic compound 6-N-hydroxylaminopurine is reported for the first time. Adenine was N-oxygenated in vitro by aerobic incubations with 3 methylcholanthrene or isosafrole induced microsomal fractions of rat liver homogenates and NADPH. The formation of 6-N-hydroxylaminopurine in the incubation mixtures under widely differing conditions was assayed using newly-developed, high-performance liquid- and thin-layer chromatographic methods. Optimal reaction conditions and kinetic parameters were determined. Neither superoxide anion nor hydrogen peroxide was directly involved in the N-hydroxylation reaction. Oxidases like xanthine oxidase and peroxidase (in the presence of hydrogen peroxide) did not catalyse this N-hydroxylation. The involvement of cytochrome P-450 isoenzymes in this reaction is supported by the observation that the N-hydroxylation is only observed after pretreatment of the rats with 3-methylcholanthrene or isosafrole. Other inducers (phenobarbital, ethanol, 5-pregnen-3 beta ol-20-one-16 alpha carbonitrile) were without effect. This is the first example of the microsomal transformation of an endogenous substance to a toxic derivative by usually foreign substances (xenobiotics) metabolizing cytochrome P-450 isoenzymes. The significance for the in vivo situation is discussed on the basis of the data obtained in this study. PMID- 2310419 TI - The strong binding of luzopeptin to DNA. AB - The effect of luzopeptin on the mobility of DNA in polyacrylamide gels has been determined. Experiments on a mixture of DNA fragments of various lengths have shown that the drug does not form intermolecular cross-links. Gel analysis of complexes of the drug with short DNA fragments (15-35 base pairs) reveals a ladder of discrete bands in which each band appears to correspond to the addition of a further drug molecule. The results suggest that luzopeptin binds very strongly to DNA, occupying about four base pairs and displays little or no sequence selectivity. Luzopeptin renders certain adenine residues hyperreactive to diethylpyrocarbonate, these occur in different positions to those affected by echinomycin. PMID- 2310420 TI - Stereoselective binding of the glucuronide conjugates of carprofen enantiomers to human serum albumin. AB - The stereoselective binding of carprofen enantiomers and carprofen glucuronide diastereomers to human serum albumin (HSA) was studied using an ultrafiltration method. Carprofen glucuronides exhibit a considerable and stereoselective affinity to HSA, although less than that seen for the parent enantiomers. The (S) glucuronide showed a higher binding affinity to HSA than the (R)-glucuronide. The (S)-enantiomer of unmetabolized carprofen was bound to fatty acid free HSA to a much greater extent than the (R)-enantiomer. Warfarin reduced the binding of the glucuronides to a greater extent than did diazepam, but diazepam displaced the unconjugated enantiomers to a greater extent than did warfarin. These results suggest differences in binding region between the carprofen enantiomers and their glucuronides on the albumin molecule. PMID- 2310421 TI - Inhibition of sodium-dependent L-leucine uptake in rat brain synaptosomes. AB - Synaptosomes isolated from adult rat cerebral cortices were used for studying the uptake of L-leucine by the Na(+)-dependent route. Three non-metabolizable amino acid analogues, which had been used previously to discriminate the Na(+) dependent A-type uptake system of animal cells, were employed in this study. It was found that Na(+)-dependent uptake of leucine was insensitive to inhibition by 2-aminoisobutyric acid (AIB) and N-methylaminoisobutyric acid (MeAIB) whereas N methylalanine (NMA) was markedly inhibitory. Inhibition by NMA was stereospecific -only the L-isomer had a pronounced effect. Na(+)-dependent uptake of leucine as well as its inhibition by L-NMA were rather insensitive to changes in pH from 6 to 9. Kinetic analysis of inhibition by L-NMA of Na(+)-dependent uptake revealed a non-competitive type of inhibition with a Ki value of approximately 0.5 mM. PMID- 2310422 TI - Staurosporine inhibition of intracellular free Ca2+ transients in mitogen stimulated Swiss 3T3 fibroblasts. PMID- 2310423 TI - Actions of morphine on histamine dynamics in the mouse brain: a strain comparison. PMID- 2310424 TI - Effects of plasmapheresis on familial type III hyperlipoproteinemia associated with glomerular lipidosis, nephrotic syndrome and diabetes mellitus. AB - A 59-year-old woman, one of 5 cases with familial type III hyperlipoproteinemia reported at our clinic to date, had nephrotic syndrome and diabetes mellitus, but had neither coronary atherosclerosis nor xanthoma. A renal biopsy specimen revealed a massive cluster of foam cells containing apolipoprotein B and E in the mesangial region of the kidney. A restricted diet intake combined with lipid lowering drugs such as cholestyramine, clinofibrate, and bezafibrate, in addition to methylprednisolone was not very effective in lowering serum triglyceride and cholesterol levels within physiological ranges. Therefore, plasmapheresis, using a dextran sulfate-cellulose column, was performed. Repeated plasmapheresis resulted in a marked decrease in both serum total cholesterol and triglyceride. A second renal biopsy specimen performed 2 years later revealed a marked reduction in foam cells with concurrent improvement in her nephrotic syndrome and glucose intolerance. These results suggest that familial type III hyperlipoproteinemia may be responsible for glomerular lipidosis resulting in nephrotic syndrome. They also indicate that plasmapheresis using a dextran sulfate-cellulose column is very effective in the removal of abnormal lipoproteins such as beta-very low density lipoprotein and intermediate density lipoprotein in a case of familial type III hyperlipoproteinemia. PMID- 2310425 TI - Probucol does not alter acetylated low density lipoprotein uptake by murine peritoneal macrophages. AB - It has been suggested that the anti-atherogenic effect of probucol (MDL 11,309) in familial hypercholesterolemic rabbits may be due in part to the inhibition of the uptake of modified low density lipoproteins by macrophages in the arterial wall. To test this hypothesis, mice were treated with dietary probucol (0.25%) for fourteen days, peritoneal macrophages were isolated and the uptake of acetylated low density lipoprotein (ALDL) was studied. In addition, peritoneal macrophages from control animals were treated with probucol (200 micrograms/ml) for 24 h in vitro prior to the ALDL uptake assay. The assay involved a fluorescent ALDL probe (dioctadecyltetramethylindocarbocyanine perchlorate labeled ALDL), and measurement of uptake with a flow cytometer. No differences in ALDL uptake were detected between the control macrophages and macrophages treated with probucol in vitro or macrophages taken from probucol-treated mice. PMID- 2310426 TI - Effects of cigarette smoking and dietary lipids on rat lipoprotein metabolism. AB - The effects of cigarette smoke inhalation on rat lipoprotein metabolism have been examined. Rats were subjected to cigarette smoke exposure over a 3-week period (two 1-h sessions/day) using a Bat-Mason inhalation machine. Rats exposed to cigarette smoke showed a decrease in total serum triglyceride and an increase in very low density lipoprotein cholesterol (VLDL-C). Administration of cigarette smoke to rats fed a saturated fat and cholesterol enriched diet also led to an increase in VLDL-C and a decrease in total serum triglycerides compared to controls. In addition, cigarette smoke exposure to animals fed the lipid enriched diet caused a decrease in high density lipoprotein cholesterol (HDL-C). Pair feeding experiments indicated that the increase in VLDL-C and the decrease in HDL C could not be solely attributed to the reduction in food intake and the small decrease in growth rate observed following cigarette smoke exposure. The changes observed in VLDL-C and HDL-C are at least qualitatively similar to the changes seen in human smokers compared to non-smokers. PMID- 2310427 TI - Investigation of lipid transfer in human serum leading to the development of an isotopic method for the determination of endogenous cholesterol esterification and transfer. AB - The rate at which radioactivity appeared in cholesteryl esters (CE) in whole serum and in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) when radioactively labelled free cholesterol (FC) was incubated with serum was investigated. At 4 degrees C equilibration of radioactive FC with native FC occurred, but there was no conversion to CE. At 37 degrees C CE mass increased in parallel with radioactivity in CE both in whole serum and VLDL/LDL. Incubation at 37 degrees C with an inhibitor of lecithin cholesterol acyl transferase (LCAT) abolished the increase in the total CE radioactivity and mass in serum. Transfer of CE from high density lipoprotein (HDL) to VLDL/LDL, however, continued to occur. An assay for LCAT and for cholesteryl ester transfer protein (CETP) was developed, which employed the increases in radioactive CE in whole serum and VLDL/LDL during a single incubation as indices of LCAT and CETP activity, respectively. Determination of the initial serum FC concentration allowed the expression of these activities in nmol/ml per h. References ranges were established in 62 fasting normolipidaemic men and women and increases in both LCAT and CETP were found following a fatty meal. The experiments thus provided further information about the carrier-mediated transfer of CE from its site of esterification on HDL to VLDL/LDL and formed the basis of a relatively simple assay, which has advantages over previously published methods and which may be used in clinical and epidemiological studies to elucidate the role of CETP and LCAT in atherosclerosis. PMID- 2310428 TI - Effects of total fat content and fatty acid composition in diet on factor VII coagulant activity and blood lipids. AB - In a strictly controlled cross-over study (twice 2 weeks) of 11 healthy adults, the effects of a low-fat diet (32% of total energy from fat) with a low or a high ratio of polyunsaturated to saturated fatty acids (0.28 and 0.89, respectively) were observed. Factor VII activity and antigen levels, serum cholesterol, HDL cholesterol and triglycerides were measured. Factor VII activity was determined in clotting assays using human and bovine thromboplastin (interacting primarily with activated factor VII, F VIIa), allowing differentiation between F VIIc and F VIIa. A significant decrease of F VII levels (median 11.0-14.5%, P less than 0.05) and triglycerides (median 0.22-0.27 mmol/l, P less than 0.05) was observed on both diets, while only the highly unsaturated diet reduced serum cholesterol levels (median 0.65 mmol/l, P less than 0.001). There were no significant correlations between changes in blood lipids and F VIIc. Low fat diets may reduce the risk for ischemic heart disease without lowering of cholesterol levels by eliminating states of hypercoagulability such as elevated factor VII coagulant activity. PMID- 2310429 TI - Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases. AB - Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques. PMID- 2310430 TI - Evaluation of atherosclerotic lesions using NMR microimaging. AB - Magnetic resonance imaging (MRI) has been proposed as a potential tool in the evaluation of atherosclerotic lesions. However, two basic difficulties have to date prevented the full exploitation of the potentials of this technique: the poor spatial resolution of the conventional tomographs and the wide variety of the lesions as well as their intrinsic dishomogeneity. In this study the in vitro morphology of normal and atherosclerotic vascular tissue specimens has been evaluated using a high resolution spectometer equipped with a microimaging device. Morphological features of the vessel walls as small as 10(-1) mm have been detected and the distribution of lipids and of calcified or necrotic regions has been evidenced in atherosclerotic plaques. Different techniques, such as local spectroscopy performed on volumes of 1 mm3 and localized magnetization recovery measurements, have been employed to characterize specific regions of the vessel walls from the chemical and the physical point of view. The good agreement of NMR findings with histological data allows us to conclude that NMR microimaging represents a suitable technique for the in vitro detection and characterization of atheromatous lesions. PMID- 2310431 TI - Linoleic acid, platelet aggregation and myocardial infarction. PMID- 2310432 TI - Attenuated SEPs with no latency shifts in a family with hereditary spastic paraplegia. AB - Five siblings with hereditary spastic paraplegia of autosomal-dominant inheritance were studied with somatosensory evoked potentials. Somatosensory evoked potentials were recorded from Cz', T12, and the left popliteal fossa following left posterior tibial nerve stimulation. The latency and amplitude of the corresponding potentials (i.e., P37, N20, and N7) were compared with normal values obtained from age- and height-matched controls. There was no significant difference in the values of N7, suggesting an intact afferent peripheral pathway; in contrast, the amplitudes of P37 and N20 were decreased with normal latencies. The degree of amplitude decrease correlated with the severity of vibration sense impairment in the lower limbs. These results appear to support selective axonopathy of the centrally directed axons of the dorsal root ganglion cells. Furthermore, our results suggest that different degrees of dorsal column involvement in hereditary spastic paraplegia can cause different types of somatosensory evoked potential abnormalities, namely, attenuated amplitudes with no latency shifts, as recorded in this family, and the prolonged latencies, as reported previously. PMID- 2310433 TI - Plasmapheresis with acute inflammatory polyneuropathy. AB - Eleven children with acute inflammatory polyneuropathy were treated with a short course of intensive plasmapheresis. The 5 males and 6 females ranged in aged from 19 months to 16 years (mean: 7.8 years). The interval from disease onset to the initiation of plasmapheresis therapy was less than 7 days in 5 patients and less than 2 weeks in the others. At the time of the first plasmapheresis, 3 patients were on respirators (Grade 5 on the Guillain-Barre syndrome scale 0-6); 7 were bedridden (Grade 4); and 1 required assisted ambulation (Grade 3). One week after the last plasmapheresis, all but 1 patient had improved by 1 or more grades on the Guillain-Barre syndrome scale. At subsequent examination 6 months later, all patients were ambulatory and 9 of 11 had no significant neurologic findings. Electrophysiologic studies performed shortly before treatment initiation revealed predominant demyelinating neuropathy in 9 and axonal changes in 2. During the 76 plasmapheresis procedures, no severe complications were encountered. Although the number of patients treated is small, the clinical response observed would indicate plasmapheresis to be a safe and effective therapy in children with acute inflammatory polyneuropathy. PMID- 2310434 TI - Epilepsy in children with attention deficit disorder: cognitive, behavioral, and neuroanatomic indices. AB - Our study examined the hypothesis that if epilepsy adversely influences the cognitive and behavioral performance of children, then children with both attention deficit-hyperactivity disorder and epilepsy (ADHD-Sz) should exhibit more severe cognitive and behavioral difficulties and be more likely to demonstrate abnormalities on cranial computed tomography than ADHD children without epilepsy. We compared ADHD-Sz and ADHD patients using a variety of psychologic, behavioral, and educational measures, as well as cranial computed tomography. ADHD-Sz children scored significantly below the ADHD group on the Wechsler Intelligence Scale for Children-Revised (performance and full scale scores). In both ADHD-Sz and ADHD groups, the prevalence of learning disabilities (LD) and a variety of behavioral features were similar. Neither seizure disorder nor ADHD was associated with an increased incidence of structural abnormalities or asymmetries of the brain. These findings support the belief that epilepsy adversely affects IQ but does not appear to affect the prevalence of LD or behavioral abnormalities in ADHD children. They further support the accumulating body of data demonstrating normal brain anatomy in ADHD by computed tomography. PMID- 2310435 TI - Moyamoya disease presenting with chorea. AB - Three children with moyamoya disease are reported whose initial and predominant manifestations were choreic movements. Two of the patients presented with unsteady gait and the other with clumsiness. Choreic movements were recurrent and were often triggered by excitement, emotional tension, or crying. They occurred unilaterally or bilaterally and often alternated between the right and left. Moyamoya disease must be considered in the differential diagnosis of acquired chorea in children. PMID- 2310436 TI - Brain death in infants: sensitivity and specificity of current criteria. AB - Guidelines for the determination of brain death in children were recently published by a multidisciplinary task force. We report a 3-month-old female who fulfilled these criteria but regained partial cortical and brainstem function for a prolonged period. This patient and similar newborn patients are analyzed with respect to sensitivity and specificity of the suggested criteria. Caution is recommended in assuming irreversibility of absent cerebral function in young infants, even beyond the neonatal period. PMID- 2310437 TI - Megalencephaly secondary to occlusion and stenosis of sigmoid sinuses. AB - Bilateral, idiopathic, essentially asymptomatic but hemodynamically significant stenosis or occlusion of the sigmoid sinuses is extremely rare. We report a child with the angiographic features of occlusion of the right sigmoid sinus and severe stenosis on the contralateral side, presenting with megalencephaly and a cranial bruit. Cranial computed tomographic scans demonstrated increased subarachnoid spaces and borderline ventricular enlargement. PMID- 2310438 TI - Etiology of intellectual impairment in Duchenne muscular dystrophy. AB - The precise etiology of intellectual impairment in Duchenne muscular dystrophy (DMD) is unknown. Histopathologic and computed tomographic studies have revealed structural brain changes; however, to our knowledge, no cranial magnetic resonance imaging (MRI) studies have been performed on DMD patients to further delineate these structural changes. We prospectively studied 4 DMD patients by cranial MRI, DNA deletion analysis, clinical evaluation, and intelligence testing. There was no significant correlation between verbal intelligence scores and MRI findings, DNA deletion, or the clinical severity of the disease. These first MRI studies of DMD did not reveal any significant anatomic brain alteration, other than mild atrophy in 2 patients. We believe these results must be considered when investigating the etiology of intellectual impairment in DMD in future studies with larger patient samples. PMID- 2310439 TI - Pituitary enlargement due to lingual thyroid gland and primary hypothyroidism. AB - Pituitary enlargement can occur as a result of primary hypothyroidism. We present a newborn with pituitary enlargement and congenital hypothyroidism secondary to a lingual thyroid gland. Thyroid hormone therapy caused a regression of pituitary enlargement. PMID- 2310440 TI - Brain death secondary to arteriovenous hemangioma of the forearm. AB - We describe the association of brain death in an infant with a large cutaneous hemangioma of the forearm. The irreversible cerebral injury is presumed to be secondary to cerebral hypoperfusion as a result of a combination of systemic hypotension and a systemic vascular "steal" phenomenon caused by the cutaneous hemangioma. PMID- 2310441 TI - Congenital myopathies. PMID- 2310442 TI - Technology: a good servant, but a bad master. PMID- 2310443 TI - Osteochondritis dissecans of the trochlea of the femur. AB - This article defines the characteristic features of osteochondritis dissecans of the trochlea of the femur, and indicates that important differences distinguish it from the more familiar femoral condylar form. The clinical features in 16 knees included: gradual onset of symptoms, pain with running and jumping, no significant history of injury; inconstant tenderness of the trochlea, and pain with resisted extension at 20 to 45 degrees. Diagnosis was usually difficult, and was often delayed because of subtle radiographic changes. Treatment depended on the stage of presentation. Nonsurgical treatment failed in four of seven knees. Drilling the lesions failed in two of the three cases. Fixation with small screws produced two good results; two others healed, but with short follow-up. Removal of the loose bodies from six knees produced one poor result and five good results. This process differs in presentation from femoral condylar osteochondritis dissecans. Although the results (average follow-up more than 5 years) were generally good, the mild symptoms probably represent incongruity of the patellofemoral joint, and probably foretell osteoarthritis. PMID- 2310444 TI - Arthroscopic synovectomy. AB - This study was undertaken to evaluate the efficacy of knee synovectomy with arthroscopic technique. Nineteen patients with 25 operated knees were studied. All 25 knees had 6-month follow-up, 21 knees had 2-year follow-up, and 14 knees were evaluated at least 4 years after operation. After operation, patients were evaluated using clinical data including pain relief, functional capacity, range of motion, recurrent synovitis, and presence of effusion. Preoperative as well as follow-up weight-bearing radiographs were also studied to assess the results of this procedure. At 6 months' postoperative clinical evaluation, 96% of patients showed good results. At 2 years, 90% of patients were considered to have good results, and at 4 years, 57% of patients continued to do well. Of those knees studied radiographically, 81% showed no progressive radiographic changes at 2 years and 61.5% showed no deterioration at 4 years. Clinical results correlated well with radiographic results. Arthroscopic synovectomy yielded results similar to those previously published for open synovectomy, with less operative and postoperative morbidity. PMID- 2310445 TI - Chondral lesions of the patella evaluated with computed tomography, magnetic resonance imaging, and arthroscopy. AB - In a small series of cadaver knees, experimentally created lesions of the patellar cartilage were compared using contrast computed tomography (CT) and magnetic resonance (MR) imaging. Contrast CT was able to recognize only 50% of the lesions smaller than 3-mm diameter at the first attempt, and none of the lesions of 0.8 mm. MR imaging detected all the lesions, even those as small as 0.8 mm, without use of contrast material. Simultaneously, a prospective clinical study comparing MR diagnoses of chondral lesions with arthroscopic findings was initiated in a series of 54 knees. This clinical study revealed that, concerning patellar chondral lesions, the accuracy of MR imaging compared with arthroscopy (the gold standard) was 81.5%. The sensitivity was 100%, but the specificity only 50% due to the false positives. Reexamination of the MR records enabled us to refine the MR diagnosis and to propose a staging of the chondral lesions. The high rate of false-positive results in our series can be explained by the hypothesis that MR imaging can possibly detect very early lesions, which appear as abnormalities in the deep cartilage layers. PMID- 2310446 TI - Precautions for arthroscopy of the wrist. PMID- 2310447 TI - The role of arthroscopy in the problem total knee replacement. AB - Fourteen patients were retrospectively reviewed to examine the role of arthroscopy in the diagnosis and treatment of the problem total knee arthroplasty (TKA), and to define parameters for indications, techniques, and results. All patients had undergone a previous TKA, and postoperatively had problems with pain and/or range of motion. Routine evaluation failed to reveal sepsis or aseptic loosening. Arthroscopy was used to evaluate and treat certain specific conditions. The arthroscope was successful in removing loose bodies, correcting patella subluxation with an arthroscopic lateral release, excising a symptomatic pseudomeniscus, and releasing intraarticular adhesions to improve motion and relieve pain. The postoperative knee score improved 73%. Arthroscopy is a valuable tool to evaluate a painful TKA, and can be used to treat certain conditions that would otherwise require an arthrotomy. The rehabilitation time is easier on the patient and much quicker. Arthroscopy of a TKA does not compromise any future procedures. However, it remains a technically demanding procedure whose indications and expectations are still being defined. PMID- 2310448 TI - Bupivacaine use after knee arthroscopy: pharmacokinetics and pain control study. AB - Bupivacaine (Marcaine) pharmacokinetics were determined in 11 patients receiving the drug intraarticularly after arthroscopic procedures performed on the knee with patients under general anesthesia. Forty milliliters of 0.25% bupivacaine (100 mg) were given as a bolus into the intraarticular space of the knee of each patient. The thigh tourniquet was released 2-3 min after injection and blood samples were obtained 5, 10, 15, 20, 30, 60, 120, 180, 250, and 300 min after tourniquet release. Pharmacokinetic parameters obtained were (mean +/- SD): Vd beta 206 +/- 88 L; Cle 0.816 +/- 0.378 L/min; t 1/2 beta 189 +/- 84 min; ka 9.92 +/- 6.79 x 10/min; Cpmax 0.48 +/- 0.20 micrograms/ml; and tmax 43.4 +/- 23.1 min. Correlations between higher peak plasma concentrations and longer tourniquet times (p = 0.02) and shorter intervals from injection to tourniquet deflation (p = 0.03) were found using multiple linear regression. Our results indicate that injections of 100 mg of bupivacaine intraarticularly after knee arthroscopy will produce peak blood levels within the 1st h after surgery and that these levels will be well below those noted to produce toxic reactions. Peak levels can be minimized with shorter tourniquet inflation times and with longer injection to tourniquet release intervals. Ninety healthy adult outpatient knee arthroscopy patients also were studied to evaluate the effectiveness of bupivacaine in relieving postoperative knee discomfort when injected immediately postoperatively. The subjects were randomized into four groups: (a) intraarticular injection of saline, (b) intraarticular injection of bupivacaine, (c) subcutaneous injection of bupivacaine at the portal sites, and (d) both intraarticular and subcutaneous injection of bupivacaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310449 TI - Blood levels of bupivacaine after arthroscopy of the knee joint. AB - Toxic levels of bupivacaine have been reported in other types of surgery, but have not been previously noted in arthroscopic procedures. The purpose of this study was to evaluate bupivacaine levels after an intraarticular bolus of bupivacaine administered after arthroscopic surgery. Blood levels of bupivacaine were found to be significantly higher in patients in whom synovial surgery had been performed compared with those patients in whom the procedure involved only meniscal or articular cartilage surgery. A reduction in the bupivacaine dosage when the synovium has been resected or divided is recommended to keep the serum level below the potentially toxic range. PMID- 2310450 TI - Rupture of the labra acetabularis as a cause of hip pain detected arthroscopically, and partial limbectomy for successful pain relief. AB - We describe two patients who had pain of unknown cause in the right hip for many years. Plain roentgenograms results were normal, and arthrography did not reveal any abnormal findings. Because clinical examinations strongly suggested internal derangement of the hip, arthroscopies of the hips were performed. The labra acetabularis were observed to be ruptured at the posterior margin of the acetabulum. Partial limbectomies were performed by the posterior approach, and the patients showed marked decrease in hip pain postoperatively. This report shows that a solitary lesion of fibrocartilaginous tissue of the hip can cause hip pain. These conditions can be easily misdiagnosed as sciatica. PMID- 2310451 TI - The lunatohamate articulation of the midcarpal joint. AB - Sixty-one cadaveric wrists were dissected to assess the frequency of a medial lunate facet as well as any associated pathologic changes in the midcarpal joint. Two types of lunate were identified: Type I (39.3%), in which no medial facet was present, and Type II (60.7%), in which there was a medial facet. The medial facets in the Type II lunates ranged from a shallow 2 mm facet to a deep 6 mm facet. Significant cartilage erosion with exposed subchondral bone at the proximal pole of the hamate, which was not identifiable by radiograph, was evident at dissection in 57% of the Type II lunates, whereas none (0%) of the Type I lunates had such associated hamate pathology. Midcarpal joint arthroscopy appears to be the diagnostic procedure of choice to assess the presence of hamate proximal pole arthrosis. PMID- 2310452 TI - Arthroscopic acromioplasty: extravasation of fluid into the deltoid muscle. AB - We studied 25 patients who underwent an arthroscopic examination of the shoulder and in whom 20 had an arthroscopic acromioplasty. In all patients there was extravasation of fluid due to the use of pressure irrigation. The pressures rose from a baseline of 12 mm up as high as 120 mm of mercury. Within 4 min of the procedure, the pressures had returned to the baseline. No patients showed evidence of muscle damage during electromyograms done at 4-6 weeks postoperatively. Pressure irrigation appears to be safe for subacromial decompression. PMID- 2310453 TI - Arthroscopic assisted rotator cuff repair: preliminary results. AB - Arthroscopic assisted rotator cuff repair is a method of performing an arthroscopic subacromial decompression with repair of the rotator cuff through a limited deltoid splitting approach. We evaluated 25 patients with a minimum of 1 year follow-up. Based on the UCLA shoulder rating, 80% of the patients were rated as excellent or good. There was significant improvement in pain, function, motion, and strength. Ninety-six percent of the patients were satisfied with the procedure. Of the patients with small or moderate size tears, 100% received a satisfactory rating. Arthroscopic assisted rotator cuff repair is presented as an attractive alternative in treating symptomatic patients with complete tears of the rotator cuff. PMID- 2310454 TI - Arthroscopic excision of synovial hemangioma of the knee. AB - A synovial hemangioma in the knee joint of a 33-year old woman was diagnosed and removed arthroscopically. Preoperatively, this rare benign soft tissue lesion had caused recurrent swelling of the knee along with persistent pain and occasional buckling. Two years after surgery, the patient has a painless range of motion with no evidence of recurrence. PMID- 2310455 TI - ACL reconstruction in animals. PMID- 2310456 TI - [Increasing chemosensitivity to cisplatin by glutathione depletion with buthionine sulfoximine. In vitro and in vivo studies with a human squamous cell cancer line]. AB - The success of antineoplastic chemotherapy in head and neck carcinoma is limited by the insufficient primary chemosensitivity of the tumor and/or the decrease of drug efficacy in the course of treatment. As regards cisplatin (CDDP) this phenomenon of chemoresistance may be closely associated with glutathione (GSH) metabolism since GSH is responsible for the detoxication of active CDDP hydrolysates. In the human squamous carcinoma cell line HLac 79, selective inhibition of GSH synthesis by buthionine sulfoximine (BSO) led to enhanced CDDP chemosensitivity both in vitro and in vivo. Using the colony-forming assay GSH depletion of HLac 79 tumor cells of more than 90% (Table 1) resulted in a dose modifying factor of 2 (Table 2). Combined treatment of HLac 79 tumor-bearing nude mice with BSO and CDDP brought about significant increase in mean survival time (p less than 0.001) as compared to the CDDP-treated group. The possible role of BSO as chemosensitizer is discussed. PMID- 2310457 TI - [Cellular immunity in 3 siblings with cancers of the upper aerodigestive tract]. AB - Although the number of carcinomas of the upper aerodigestive tract is increasing, there are not many reports in the literature about familial occurrence. Epidemiological studies have shown that the major causative factors are tobacco and alcohol abuse. But the possibility of an endogenous susceptibility is also discussed. A possible explanation is failure of the immune defense system. The author was able to examine immunologic patterns in three siblings with cancer of the upper aerodigestive tract. The results obtained so far indicate normal numbers of lymphocyte subpopulations in the peripheral blood, but with impaired function. PMID- 2310458 TI - [Drainage of the middle ear]. AB - Otitis media with effusion occurs very frequently in childhood and usually heals without therapy. The condition is thought to be due to a higher susceptibility to infections of the upper respiratory tract and the fact that the Eustachian tube is not yet functioning perfectly at that age. Many authors explain this astonishingly high rate of spontaneous recoveries by tube malfunction alone, never even considering a middle ear clearance system. It is known from the paranasal sinuses that the cavities are regularly and continually cleaned according to very precise rules. In in-vivo experiments with guinea pigs the author proved that there is an obvious similarity between the paranasal sinus and the middle ear as far as the clearance system is concerned. By applying tracer substances to the middle ear mucosa the usual drainage pathways out of the middle ear into the Eustachian tube, and the different rates of drainage were very precisely defined. PMID- 2310459 TI - [Assessment of central disorders of the statoacusticus nerve using high resolution imaging procedures (PET and MRI)]. AB - Disorders of the auditory and vestibular central nervous system can be diagnosed more precisely by high resolution magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI is mostly used for small intrameatal acoustic neuromas up to 10 mm, intracranial cholesteatomas, and multiple sclerosis. Positron emission tomography has advantages after acoustic or electric stimulation in the auditory cortex. PET is not yet a routine procedure in clinical diagnosis. PMID- 2310460 TI - [The trigemino-facial reflex in patients with essential blepharospasm. A contribution to the etiology of the disease picture]. AB - We conducted electrophysiological investigations in altogether 11 patients with an essential blepharospasm. In all patients the blink reflex - ipsi- and contralateral - was measured. We found reproducible pathologic changes (direct R1/R2 transition, contralateral early component with and without direct transition into the R2-component, increase of R2-duration). These findings point to a central genesis of blepharospasm in some cases. PMID- 2310461 TI - [Dysarthria, dysphagia or dyspnea as a reason for the initial consultation in pseudoparalytic myasthenia gravis and amyotrophic lateral sclerosis]. AB - In myasthenia gravis and amyotrophic lateral sclerosis the ENT specialist or the phoniatrician may be consulted first, because in about 30 percent of all cases the initial symptoms are dysarthria, dysphagia or dyspnea. Three typical cases of each condition are presented. The quality of life of the patients can be improved considerably by early diagnosis and treatment. Special diagnostic and therapeutic procedures are described. PMID- 2310462 TI - [Microsurgery of the nasal cavity and paranasal sinuses]. AB - Out of a total of 295 cases in which endonasal microsurgery of the nasal cavity and the paranasal sinuses was performed, 221 were submitted to a detailed analysis. Compared with transfacial sinus surgery, the rate of complications was significantly lower. Further advantages of the transnasal microsurgical technique are better functional results, considerably fewer complaints during the postoperative period, and a reduced duration of hospitalization. PMID- 2310463 TI - [Aerodynamics of respiratory flow in the nasopharynx]. AB - The authors present a new technique for studying airflow patterns and particle deposition in the nasopharynx. The nasal cavities and the nasopharynx from the head of a human cadaver were filled with siliconrubber and a "positive" model was then produced by moulding with plastic. An apparatus was constructed to provide calibrated flow of propandiol in both directions. Flow characteristics were visualized by introducing small particles in suspension or by injecting methylene blue with a needle. In addition, test aerosol was drawn in through the model to demonstrate dust deposition sites in the nasopharynx. In the future, this method will enable us to examine the nasopharyngeal airflow patterns and deposition sites of inhaled particles. PMID- 2310464 TI - [Considerations and studies of the classification of glottis cancers]. AB - Since 1972, the principles of the T classification of glottic carcinomas have remained unchanged. Nevertheless, discrepancies between T-classification and post therapeutic pT classification are reported repeatedly and doubts have been expressed about the reliability of this system. Our T classification is based on pathohistological investigations performed 20 years ago. Therefore, the origin of the above-mentioned discrepancies must be sought in the definition and the clinical diagnostics. First, problems of the T classification of glottic cancer are analyzed and discussed on the basis of conditions which must be fulfilled by each classification: (1) clearly defined boundaries of the anatomical regions; (2) clearly defined rules for classification; (3) practicability for the clinician as well for the pathologist and comparability for both, and (4) prognostic relevance. Second, a new definition of the glottic region is proposed. It should be confined to the extension of the vocal ligaments, their anterior commissure and the medial surface of the arytenoid cartilages, including Reinke's space and the epithelial layer covering all the described areas. This is because the glottic region is confined to anatomical areas with reduced lymphatic drainage and a connective tissue barrier. The proposal is based on an anatomical and morphometric investigation of 154 larynx specimens. Third, 403 glottic carcinomas, treated between 1970 and 1984 were classified by the current T classification and histologically by pT classification (UICC 1987). By comparing these two classifications it was established that the early carcinomas had been overestimated and the advanced carcinomas underestimated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310465 TI - [Removal of the sural nerve]. PMID- 2310466 TI - Breast exam--a new perspective. AB - This article is designed to help nurses differentiate normal and abnormal breast tissue. Consistency, mobility, location, size, shape, and tenderness of normal breast tissue are described. This will assist nurses with their skill, patient education and their own personal health practices. PMID- 2310467 TI - Nurse in day care. AB - This article describes the role of the day care center nurse consultant. PMID- 2310468 TI - Cardiac catheterization--before and after. What the patient should understand! What the nurse needs to know! AB - This article provides helpful cardiac catheterization information for nurses preparing patients for this procedure and administering follow-up care. Pre-cath and post-cath teaching information and discharge instructions are included. PMID- 2310469 TI - Dealing with obnoxious people. AB - Techniques and suggestions in dealing with the problem behaviors of others are presented. The importance of human power, objectivity, and a positive attitude in the work place is highlighted. PMID- 2310470 TI - Call that code! Simulated code practices. AB - This article deals with the planning and implementation of simulated code blue practice sessions for licensed staff. Use of situational role play utilizing the actual equipment is emphasized. Strategies for implementing a program as well as strengths and weaknesses of one such program are discussed. PMID- 2310471 TI - Hypothyroidism. PMID- 2310472 TI - Soviet nurses and health dignitaries arrive in the US. PMID- 2310473 TI - How to face (and defuse) an angry family. "A communication skit". PMID- 2310474 TI - So you want to float. AB - This article describes the benefits and challenges of floating. PMID- 2310475 TI - [Therapeutic approach for nasal sinus polyposis]. AB - The multiple etiologies of bilateral naso-ethmoidal polyposis (PNE) make a precise and regulated therapeutic decision difficult. The treatment is chosen after a clinical history, radiology and complete biological investigation. Medical and surgical treatments share the indications. Medical treatment is dominated by local corticotherapy. Its failures and recurrence following its end may suggest general corticotherapy, an efficacious remedy but which carries well known risks. The choice of treatment is guided by whether the characteristics of the polyposis are invalidating or not. The localised forms often respond to local medical treatment. Invalidating polyposis continues to be difficult to treat, especially where there is intolerance to aspirin. Corticotherapy by the general route, even sequential, remains insufficient to be sure of long asymptomatic periods. We suggest for these patients a clear ethmoidal once or twice under local anaesthetic with diazanalgesia. The local treatments associated with corticotherapy and anti histamines help the healing of the operated cavity. Crenotherapy is an useful aid after having obtained clean, permeable nasal fossae. The choice remains empirical and is a function of the group, but it must not include iatrogenic risks greater than those of the illness itself. We report our actual experience. PMID- 2310476 TI - [Perennial rhinitis from food allergy]. AB - Food allergy (AA) is involved in a third of subjects with perennial rhinitis (RPA). The majority of the patients are polysensitized. Isolated food allergy was only seen in 6 of 261 cases, which indicates an association of food allergy with other allergens, essentially pneumo-allergens. Immediate diagnosis of AA in RPA is difficult as it is essentially based on tests of elimination and re introduction of the food, skin tests and RAST. PMID- 2310477 TI - [Allergic rhinitis in the horse: first case]. AB - The responsibility of the artificial environment in the development of respiratory allergy in horses is well known as the most important factor for the development of asthma, chronic dry cough and pulmonary emphysema. One case of allergy to the natural environment could be observed. One allergic rhinitis with asthma could be explored. Pathology, cause, tests and specific immuno-therapy are presented. PMID- 2310478 TI - Twenty years' perspective on progress. PMID- 2310479 TI - Bottle-feeding like a breastfeeder: an option to consider. PMID- 2310480 TI - A policy for supplementary/complementary feedings for breastfed newborn infants. PMID- 2310481 TI - The galactopharmacopedia. Recreational drug use in the breastfeeding mother. Part 2: Licit drugs. PMID- 2310482 TI - The unknown human infant. AB - What is physiological? It is often difficult to answer this kind of question in the field of human reproduction. That is why we propose to take, as a reference, a population of one hundred infants whose lifestyle is, in many respects, different from the standard Western norm. They were born at home without any drugs, share the mother's bed, were breastfed for more than a year, and so on. This study raises questions such as: --Is the neonatal loss of weight physiological? --What are the physiological sleep-wake patterns of the human infant? --Are the transitional phenomena normal stages of human development? - Why are some infants ill when their mother loses weight? PMID- 2310483 TI - "Incidental" maternal dietary intake and infant refusal to nurse. PMID- 2310484 TI - Gift certificates for promoting breastfeeding. PMID- 2310485 TI - Linguistic analogies and behavior: the finite-state behavioral grammar of food hoarding in hamsters. AB - Rodger and Rosebrugh (1979) developed a method for identifying sets of rules by which discrete responses are combined to form functional sequences of behavior. In the present study, this so-called finite-state behavioral grammar method was used to analyze the food-hoarding behavior of Syrian golden hamsters (Mesocricetus auratus). Specifically, it was used to analyze 127 videotaped food hoarding sequences that were observed in 14 male, adult hamsters in an apparatus that comprised a home compartment, a foraging area, and a connecting tunnel. An integral part of grammar derivation is the development of hypotheses about the function of the observed response patterns to guide the grammar derivation. Two such hypotheses guided the present analysis: first, we hypothesized that behaviors observed in the foraging area after the hamsters' cheek pouches were filled served an exploratory function; second, we hypothesized that behaviors observed in the home compartment prior to the hamsters emptying their cheeck pouches served to assess potential food deposition sites. In addition to generating these two hypotheses and the grammars for the hoarding sequences, this study demonstrates how the finite-state grammar method can be used as a productive means of gaining insights into the organization of consummatory response sequences. PMID- 2310486 TI - Reinforced alternation performance is impaired by muscarinic but not by nicotinic receptor blockade in rats. AB - In pre-trained rats, food-rewarded reinforced alternation in a T-maze was markedly impaired by scopolamine, but unaffected by the centrally-active nicotinic antagonist mecamylamine (0.2-6.3 mg/kg s.c.). The nicotinic antagonist chlorisondamine (10 micrograms i.v.t.) was also ineffective, despite demonstrated blockade of nicotine-induced locomotor depression. These results question the extent to which central nicotinic receptors are involved in memory function. PMID- 2310487 TI - Rats exposed prenatally to alcohol exhibit impairment in spatial navigation test. AB - Prenatal exposure to ethanol causes learning disabilities and low I.Q. scores. The objective of the present studies was to investigate whether exposure of rats to ethanol in utero, would induce a deficit in spatial memory in adult life. Pregnant rats were fed with an ethanol diet from day 1 of pregnancy till parturition. Control rats were either pair-fed with an isocaloric sucrose diet or were fed with lab-chow ad libitum. On the first day of birth, offspring exposed to ethanol in utero were placed with a control mother fed with lab-chow, while offspring of the lab-chow fed dams were placed with ethanol-treated dams. At 40, 60 and 90 days postnatally, behavioral testing was performed using the Morris swim maze, a test of spatial memory. Results indicated that the offspring exposed to ethanol in utero presented deficits in spatial memory processes. Ethanol did not completely block the learning of the swim maze task but the alcohol-exposed offspring exhibited longer latencies to perform the task, swam longer distances prior to locating and climbing onto the platform, and when the platform was removed, searched for it in all 4 quadrants of the pool. Restricted caloric intake during gestation and maternal behavior in early postnatal life also induced deficits in the performance on the swim maze task. However, these deficits were mild and short-lasting being absent at 60 and 90 days of age. In contrast, the deficits induced by ethanol were more severe and longer-lasting, being present in adult life. PMID- 2310488 TI - The effects of ibotenic acid lesions of the nucleus basalis and cholinergic-rich neural transplants on win-stay/lose-shift and win-shift/lose-stay performance in the rat. AB - Rats were trained to criterion performance in 2-lever operant conditional memory tasks that required them to follow either a Win-stay/Lose-shift, or else a Win shift/Lose-stay response rule. Substantial impairments in performance of both pretrained conditional tasks were seen following ibotenic acid lesions of the nucleus basalis, but not of the globus pallidus. The deficit in both tasks was apparent at all inter-response retention intervals, indicating that nucleus basalis lesions produced a general impairment in the performance of the complex conditional operant tasks, and not a specific deficit in short-term memory. The nucleus basalis lesion rats were then divided into groups matched for equivalent performance. One group was given cell suspension grafts into neocortex of E15 cholinergic-rich forebrain tissue; a second group was given similar grafts of E17 hippocampal tissue; and a third group was given sham transplants. Testing beginning 3 months post-transplant showed that there was no evidence of recovery of performance on these tasks in the cholinergic-rich transplanted groups compared to the controls. However, the rats with cholinergic-rich transplants subsequently showed a significant improvement in retention of a step-through passive avoidance task. The results indicate that either cholinergic deafferentation of the neocortex is not critical for the observed deficits in the operant conditional tasks, or recovery of function following cholinergic-rich transplants is task-specific, in that more complex cognitive tasks may require different levels of graft-host neural integration. PMID- 2310489 TI - Behavioral characterization of intracranial self-stimulation from mesolimbic, mesocortical, nigrostriatal, hypothalamic and extra-hypothalamic sites in the non inbred CD-1 mouse strain. AB - A behavioral analysis of intracranial self-stimulation (ICSS) was provided for mesolimbic/mesocortical, nigrostriatal, hypothalamic and extrahypothalamic sites in the CD-1 mouse. Robust responding and rapid acquisition of mesocortical ICSS appeared dorsally along notably fluorescent sites in rostral and caudal planes. ICSS was diminished demonstrably in medial and ventral positions in posterior planes. Mesolimbic ICSS from the medial and ventral nucleus accumbens (Nas), was accompanied by significant elevations in locomotor activity, corresponding to regions of dopamine (DA) and cholecystokinin co-localization. Stimulation-induced seizures appeared from both the Nas as well as the mesocortex. ICSS from the ventral tegmental field (VTA) was evident along its medial, lateral and dorsal borders with longer pulse durations more likely to elicit responding. Seizure activity was absent from the VTA. Striatal ICSS was conspicuously poor in dorsal and medial locations; regions presumably devoid of tegmental innervation. ICSS emerged from both the ventrocaudal and anteromedial striatum; regions linked to innervation by the dorsolateral and ventromedial VTA. The red nucleus, a previously neglected self-stimulation site supported marked responding for ICSS. Regions supporting rubral ICSS were correlated with thalamic innervation sites; notably the ventrolateral thalamic nucleus and the parafascicular nucleus, regions found to support ICSS. The substantia nigra supported high rates of responding for ICSS when electrode placement was restricted to the dorsomedial portion of the pars compacta. Electrode deviations lateral and dorsal to the substantia nigra pars medialis induced a progressive decline in responding. Hypothalamic sites were found to support significant responding for ICSS, although such performance was frequently associated with seizure induction. Taken together these data (1) provide the first behavioral analysis of ICSS in mice responding from previously unexamined DA sites in the mesolimbic (e.g. VTA, Nas) and nigrostriatal systems (e.g. caudate, red nucleus) (2) suggest an anatomical reconsideration of the assumptions underlying the elicitation of ICSS from the frontal cortex (3) suggest that the neural circuitry underlying thalamic, caudate, rubral and frontal cortical ICSS are interrelated and (4) suggest that the Nas and the frontal cortex, like the hypothalamus, in the mouse appear to be particularly sensitive to stimulation-induced seizures. PMID- 2310490 TI - Task difficulty increases thresholds of rewarding brain stimulation. AB - The effect of increasing task difficulty on the threshold of rewarding, electrical brain stimulation was evaluated. Rats were trained to press a lever to obtain a brief burst of pulses to the lateral hypothalamus. The threshold was psychophysically scaled using a descending method of limits in which the pulse frequency was varied to yield a maximum to minimum range of self-stimulation rates. As expected, weighting the lever with 0, 15, 30, or 45 g produced progressive decreases in maximal rates, but it also caused a weight-related shift to the right of the rate-frequency ogives in each of the 7 rats. Although the degree of shift varied from rat to rat, it did not matter whether criterion performance was defined as half-maximum rate or as a constant rate of 5 responses. These results suggest that the effort required to make the operant response contributes to the position of rate-frequency curves and, further, that shifts in rate-frequency functions must be interpreted with caution when such shifts are obtained by CNS lesions or drug injections. PMID- 2310491 TI - Central catecholaminergic dysfunction and behavioural disorders following hypoxia in adult rats. AB - Wistar male rats, 3-4 months old, were made to breathe for 6 h a sub-lethal hypoxic atmosphere consisting of 8% oxygen and 92% nitrogen. Following this treatment, these rats were subjected to a series of behavioral and biochemical tests starting 30 days and ending at about 180 days after the hypoxic insult. an age-matched control group was subjected to the same series of tests. The following findings were made at the time interval indicated, relative to controls: (1) At 30-35 days, diurnal (3 h) and nocturnal (12 h) locomotor activities decreased by about 25%. (2) At 40-45 days, amphetamine in the dose range of 0.25-1 mg/kg proved less effective in eliciting an increase in motor activity and stereotypic behavior. (3) At about 50 days, apomorphine in the dose range 0.25-0.5 mg/kg caused an increase in stereotypic behavior. (4) At 60-65 days, alpha-methyl-p-tyrosine at the dose of 50 mg/kg caused a more pronounced hypoactive syndrome and a slower rate of recovery of motor activity. (5) At 75-90 days, performance in the active avoidance test was inferior to that of controls. (6) At 180 days, and one hour after a dose of 200 mg/kg alpha-methyl-p-tyrosine, the turnover rates of hippocampal norepinephrine and caudate-putamen dopamine were much below control. One may tentatively conclude that one of the effects of hypoxia in adult rats is a lesion producing long-term behavioral disorders which are partly ascribed to dopaminergic and, possibly noradrenergic, dysfunction. PMID- 2310492 TI - Visual and auditory delayed discriminations in male and female Wistar rats. AB - Different groups of male and female Wistar rats were exposed to a discrete-trial delayed discrimination procedure, in which subjects were required to discriminate between a continuously or intermittently presented visual (half of the subjects) or auditory (other half of the subjects) stimulus. The opportunity to respond was delayed for 0, 5, 10 or 20 s after stimulus presentation. Both response levers were inserted into the experimental chamber immediately upon the termination of the delay interval. A press on the left lever was followed by food if the continuous stimulus had been presented, while food was presented following a press on the right lever if the intermittent stimulus had been presented. During sessions 1-60, each incorrect response or failure to respond during the 5-s lever presentation was followed by presentation of the same visual or auditory stimulus, and the same delay interval, once the intertrial interval was terminated. This sequence was repeated until a correct response occurred. During sessions 61-90, repeated presentations of the same trial following incorrect responses or a failure to respond on initial trials were no longer presented. All other experimental contingencies remained unchanged. Response accuracy increased with prolonged training. Subjects exposed to the visual delayed discrimination procedure showed less accurate performance than subjects who were exposed to the auditory delayed discrimination procedure. Response accuracy was higher when the delay interval was short than when it was long. Males made more correct responses than females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310493 TI - The postnatal development of the air-righting reaction in albino rats. Quantitative analysis of normal development and the effect of preventing neck torso and torso-pelvis rotations. AB - The aim of this study was to describe the ontogenesis of the air-righting reaction (ARR) in rats. The first experiment was performed on 6 newborn albino rats of both sexes and followed the development of the ARR over postnatal days 1 21. The degree of rotation achieved after falling from different heights was quantified according to a rating scheme. It appeared that the air-righting reaction is effected by a spiral movement which spreads in a cranio-caudal direction. The reaction develops between postnatal day 8 and 18. On postnatal day 10 only a few animals are able to turn their heads, this being possible only from a falling height of 60 cm and corresponding to a falling time of 350 ms. A rapid development of the reaction was found between days 10 and 14. The second experiment on 8 rats involved the use of immobilization in order to isolate the mechanisms that trigger the ARR. The immobilization prevented neck-torso rotation, torso-pelvis rotation, and both rotations in different animals. Despite the disruption of important (afferent) feedback systems, the reaction developed within the same age period as in control rats. Thus, the Magnus "chain reflex hypothesis' as basis for the ARR is rejected in favor of a central motor program hypothesis. PMID- 2310494 TI - Chronic infusion of GABA and saline into the nucleus basalis magnocellularis of rats: II. Cognitive impairments. AB - In order to assess sensorimotor and/or cognitive modifications following chronic inhibition of nucleus basalis magnocellularis (NBM) neurons, rats trained in two radial maze paradigms (the classical version of the test and a modified version introducing a one-hour delay between the fourth and the fifth choice) received chronic infusion of gamma-aminobutyric acid (GABA) into the NBM area. GABA (10 and 50 micrograms/microliters/h) was infused for 3 days into the NBM contralateral to their preferred turning direction in the radial maze. Simultaneously, saline (NaCl 0.9%; 1 microliter/h) was infused into the contralateral NBM. GABA and saline infusions were alternated for the subsequent 3 day period. One week later, we investigated the rats' ability to learn a multiple trial passive avoidance task. At the dose of 50 micrograms/microliters, GABA infusion produced (1) a turning bias ipsilateral to the side first infused with GABA, (2) transitory cognitive impairments in radial maze tasks and (3) a deficit in the acquisition of the passive avoidance task. At the dose of 10 micrograms/microliters, the same behavioral deficits were observed except that (1) the turning bias was reversed by the contralateral GABA infusion and (2) cognitive impairments in the radial maze were observed only when a delay was inserted between the fourth and the fifth choice. Histologically, we found a dose dependent gliosis in the NBM area first infused with GABA. These data suggest a reactivity of the NBM to GABAergic manipulations and the intervention of this structure in both sensorimotor and cognitive processes involved in the radial maze paradigms. PMID- 2310495 TI - Hippocampus, amygdala, and memory deficits in rats. AB - Five experiments were conducted to compare the contribution of the hippocampal formation and amygdala to mnemonic processes. The performance of rats with damage to the hippocampal formation or amygdala was examined in tests of visual and olfactory non-matching-to-sample with familiar items, cross-modal association, gustatory neophobia, topographical memory, autonomic conditioning to context, and configural discriminations. Neither lesion affects non-matching-to-sample performance. An intact hippocampal formation, but not amygdala, is necessary for cross-modal association between vision and olfaction, topographical memory, conditioning to context, and configural discrimination learning. Amygdala damage disrupted gustatory neophobia and may have impaired learning an association between an auditory cue and food reward. PMID- 2310496 TI - Similar memory impairments found in medial septal-vertical diagonal band of Broca and nucleus basalis lesioned rats: are memory defects induced by nucleus basalis lesions related to the degree of non-specific subcortical cell loss? AB - The function of nucleus basalis (NB) and medial septal-vertical diagonal band of Broca (MS-VDBB) in a place navigation task requiring reference memory was investigated. Two subclasses of nucleus basalis ibotenic acid-lesioned rats could be identified: a group having both extensive non-specific subcortical damage and severely impaired learning behavior, and a less impaired group with correspondingly less subcortical damage. The depletion of cortical cholinergic enzymes was slightly higher in the group of NB-lesioned rats with extensive subcortical lesions than in the group with smaller lesioned areas. In the hippocampus of both of these NB-lesioned groups, cholinergic innervation remained unchanged. Ibotenic acid lesioning restricted to the MS-VDBB depleted hippocampal cholinergic innervation, but not the innervation of the frontal cortex, and also led to impaired learning behavior. Of all the lesioned rats, the most impaired were the NB-lesioned rats with large non-specific subcortical lesion. PMID- 2310497 TI - Caenorhabditis elegans: a new model system for the study of learning and memory. AB - The extensive information on the neuroanatomy, development and genetics of Caenorhabditis (C.) elegans make it an ideal candidate model system for the analysis of the mechanisms underlying learning and memory. A first step in this analysis is the demonstration of the capacity of C. elegans to learn. In these experiments non-associative learning in C. elegans was investigated by observing changes in reversal reflex response amplitude to a mechanical vibratory stimulus. The results from these studies of non-associative learning show that C. elegans is capable of short-term habituation, dishabituation and sensitization, as well as long-term retention of habituation training lasting for at least 24 h. These findings set the stage for detailed developmental, genetic and physiological analyses of learning and memory. PMID- 2310498 TI - Involvement of prefrontal dopamine neurones in behavioural blockade induced by controllable vs uncontrollable negative events in rats. AB - The present study was undertaken to investigate the involvement of dopaminergic (DA) neurones afferent to the prefrontal cortex in stress-related behaviours induced by controllable vs uncontrollable negative events. Rats were either sham operated or given a bilateral infusion of 6-hydroxydopamine (4 micrograms in 0.4 microliter) into the prefrontal cortex which resulted in a specific and almost complete (80%) reduction of local DA. Three weeks after surgery, sham and lesioned rats were subjected to one of the following experimental procedures involving (1) controllable or (2) uncontrollable events: (1) the punished drinking test and a FR1/FR7 schedule of food/shock presentation; (2) the forced swimming test and the learned helplessness paradigm. DA depletion in the prefrontal cortex resulted in an increase in punished responding in the drinking test and under the FR schedule; the anti-punishment effects of diazepam (2 mg/kg) were not modified. Lesions also induced a reduction in immobility duration in the forced swimming test but failed to affect the induction of escape deficits in rats trained for learned helplessness. In the latter two models, DA depletion in the prefrontal cortex did not modify the antidepressant effects of desipramine (32 mg/kg and 24 mg/kg/day, respectively). These results suggest that controllable and acute aversive situations may be modulated by DA neurones in the prefrontal cortex. DA neurones, however, may not be crucial in the modulation of delayed and uncontrollable stress-related behaviours. Taken together, the present findings suggest that an increased tendency to perseverate could be the main behavioural feature associated with DA lesion in the prefrontal cortex. Acute vs delayed consequences of negative events could be an additional relevant factor for the involvement of DA neurons in stress-related behaviours. PMID- 2310499 TI - Responses to ethanol challenge in long- and short-sleep mice prenatally exposed to alcohol. AB - Individual sensitivity to alcohol may influence the severity of functional deficits due to prenatal alcohol exposure. To examine this hypothesis, Long-Sleep (LS) and Short-Sleep (SS) mice, selectively bred for differences in ethanol induced narcosis, were intubated with either 2.9 g/kg ethanol (E) or an isocaloric amount of sucrose (S) twice per day on days 7 through 15 of pregnancy. An untreated control group (C) was maintained for each line. Offspring were fostered to lactating Rockland-Swiss mice at birth. Males and females from each litter were challenged with an acute dose of ethanol (3.8 g/kg) at 30 days of age. Measures of sleep time duration, waking blood ethanol concentrations (BEC), rectal temperatures, heart rate, and ethanol clearance were obtained to examine whether the acute effects of ethanol are altered by prenatal alcohol exposure. Prenatal alcohol exposure did not differentially affect responses to ethanol challenge within either genotype. Ethanol-induced hypothermia, heart-rate depression, and sleep time did differ between genotypes, with LS more affected than SS mice. Ethanol clearance rates were faster for SS than LS mice. These results suggest postnatal pharmacological responses to acute ethanol challenge are not altered by prenatal alcohol exposure in LS and SS mice. Prenatal alcohol exposed offspring of both mouse genotypes showed lower average heart rate responses than controls, suggesting this measure may be a sensitive indicator of prenatal alcohol effects in mice. PMID- 2310500 TI - The effects of naltrexone on cadmium-induced increases in oral ethanol self administration. AB - Adult male rats were exposed to a standard laboratory diet (N = 20), or an adulterated diet containing 100 ppm added cadmium (N = 20), for 60 days. On Day 61, half the animals from each dietary condition received subcutaneous implants of two 30 mg naltrexone pellets, and the remaining half the animals received identical implants of 30 mg placebo pellets. One week later, animals from groups created by this interaction (Groups Control-Placebo, Control-Naltrexone, Cadmium Placebo, Cadmium-Naltrexone) were tested in an ethanol self-administration paradigm that presented a 10% ethanol solution (v/v) in both a choice and nonchoice format. The results indicated that cadmium exposure increased the oral self-administration of ethanol in the choice setting where water was offered as an alternative, and the opiate antagonist naltrexone failed to attenuate this effect. PMID- 2310501 TI - Harman (1-methyl-beta-carboline) in blood plasma and erythrocytes of nonalcoholics following ethanol loading. AB - Eleven subjects having no history of substance abuse or dependence who agreed to abstain from alcohol for one week prior to the investigation were selected to participate in the present study. On two occasions, separated by four to six weeks, blood was drawn over an 8-hour period (0, 0.5, 1, 2, 4 and 8 hours). On the first occasion, subjects were given an oral dose of ethanol (1 g/kg) after the first blood sample was drawn (ethanol-loading condition). On the second occasion no ethanol was administered (control condition). On both occasions no detectable harman was found in the plasma of subjects. In the control condition harman was detected in the erythrocytes of 7 subjects which remained relatively stable over time. In the ethanol-loading condition, however, a time-dependent increase of harman in the erythrocytes was observed. The concentration of ethanol, acetaldehyde, and erythrocyte-harman showed a parallel trend over time. These findings demonstrate an increased level of harman following ethanol loading in humans. PMID- 2310502 TI - Effects of acetaldehyde on membrane potentials of sinus node pacemaker fibers. AB - The experiments reported here were performed to characterize the effects of acetaldehyde on membrane potentials (MP) of sinus node subsidiary pacemaker fibers in the absence and presence of adrenergic and cholinergic blockade. Guinea pig sinoatrial preparations were superfused with Tyrode's solution at 37 degrees C while electrically stimulated at 5 Hz. Intracellular microelectrodes were used to record the MP of sinus node subsidiary pacemaker fibers. Acetaldehyde 3 x 10( 6) M and 3 x 10(-3) M had no effect on maximum diastolic potential (MDP), while 3 x 10(-5) M and 3 x 10(-2) M exerted a depolarizing effect on the MDP, without affecting the overshoot (OS). The fall in MDP was associated with a reduction in the amplitude of the action potential (AAP) and the maximum velocity of phase 0 (Vmax 0). The depressant effect of acetaldehyde on MDP was not abolished by adrenergic blockers or atropine. Concentrations of acetaldehyde between 3 x 10( 5) and 3 x 10(-2) M prolonged the action potential duration (APD). Acetaldehyde 3 x 10(-3) M did not affect MDP even in the presence of atropine or propranolol. The APD-prolonging effect of acetaldehyde was not abolished by adrenergic blockers. In summary, the actions of acetaldehyde on MDP and APD were independent of adrenergic and cholinergic mechanisms. PMID- 2310503 TI - Changes in blood acetaldehyde levels after ethanol administration in alcoholics. AB - Serial changes in blood ethanol (Et-OH) and acetaldehyde (Ac-CHO) levels following a single oral administration of 0.8 g/kg of Et-OH were determined in order to clarify the metabolism of Ac-CHO in alcoholic liver disease (ALD). The Et-OH metabolic rate (EMR) in alcoholics either with or without liver disease was significantly higher than the rate in nonalcoholics. Peak values of blood Ac-CHO levels and the Ac-CHO/EMR ratios in ALD were significantly higher than those in subjects with nonALD or alcoholics and nonalcoholics without liver disease. In the type I aldehyde dehydrogenase isozyme deficient cases (unusual type), blood Ac-CHO levels and Ac-CHO/EMR ratios were very high and the levels remain at a plateau until 90 minutes after Et-OH administration and then decreased relatively quickly. Changes in blood Ac-CHO levels and Ac-CHO/EMR ratios in ALD were similar to those in cases of the unusual type. These results indicate that Ac-CHO metabolism in ALD is decreased relative to its production and that this decrease might be due to increased production of Ac-CHO in the nonalcohol dehydrogenase pathway located in the microsomes, in which degradation of Ac-CHO was slow. PMID- 2310504 TI - Changes in brain microvasculature resulting from early postnatal alcohol exposure. AB - The microvasculature in selected brain regions in rats was examined on postnatal day 10 following exposure to alcohol on postnatal days 4 to 10. The alcohol exposed rats were artificially reared and given 6.6 g/kg of ethanol condensed into 8 hr of each 24-hr period. A gastrostomy-control group was reared in the same manner but maltose-dextrin was substituted for ethanol in the formula. A suckle-control group was reared normally by dams. Measurements were taken from midsagittal sections of the cerebellum and sections of the hippocampal formation at a midtemporal level. Although the overall area of the vermal cerebellum was decreased as a consequence of the alcohol exposure, the capillary density was unchanged. However, cerebellar capillary diameters were increased in some lobules in the alcohol-exposed rats. In the dentate gyrus, there was a trend toward a decrease in capillary numerical density but no change in regional area or capillary diameter in the alcohol-exposed rats. In the hippocampus proper, there was a decrease in regional area, no change in capillary density, and an increase in capillary diameter due to alcohol. These results indicate that alcohol exposure during the early postnatal period affects the microvasculature differentially in the cerebellum, hippocampus proper and dentate gyrus. PMID- 2310505 TI - Pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate concentrations in blood and tissues of mice fed ethanol-containing liquid diets. AB - The effects of chronic ethanol administration on vitamin B-6 metabolism were studied in female Long-Sleep (LS) and Short-Sleep (SS) mice. Animals were fed an ethanol containing liquid diet (AIN-76) for four weeks. Concentration of ethanol in the diet increased from 10 to 25% ethanol-derived calories (EDC) during weeks 1-3 and was maintained at 30% EDC for 1 additional week. We measured concentrations of pyridoxal 5'-phosphate (PLP) in plasma, erythrocytes and whole blood, and liver and brain PLP and pyridoxamine 5'-phosphate (PMP) in ethanol-fed and pair-fed control mice. Chronic ethanol administration significantly increased PMP and total (PLP + PMP) levels in the liver of SS mice. In LS mice ethanol feeding significantly decreased PMP and total (PLP + PMP) levels in the brain, but these values were still within normal limits. These results suggest that both control and ethanol-containing liquid diets are nutritionally adequate with respect to vitamin B-6, and that chronic ethanol administration does not adversely affect vitamin B-6 metabolism in adult mice. PMID- 2310506 TI - Developmental profile of hepatic alcohol and aldehyde dehydrogenase activities in long-sleep and short-sleep mice. AB - Ethanol is metabolized primarily in the liver by a cytosolic alcohol dehydrogenase (ADH). The product, acetaldehyde, is metabolized to acetate by nonspecific aldehyde dehydrogenases (AHD). Mouse liver contains five major constitutive AHD isoenzymes: mitochondrial high Km (AHD-1), mitochondrial low Km (AHD-5), cytosolic high Km (AHD-7), cytosolic low Km (AHD-2) and microsomal high Km (AHD-3). The Long-Sleep (LS) and Short-Sleep (SS) mice differ in their sleep time response to ethanol as early as 10 days of age, and this difference increases with increasing age. Age- and genotype-related differences in metabolism could account for the pattern of responses seen in these mice. We measured the activity of hepatic ADH and the five AHD isoenzymes in LS and SS mice from 3 days of age to adulthood to determine if there were differences in the developmental profiles of these enzyme activities. We found no sex differences in the developmental profile of either ADH or AHD, and the LS and SS mice have nearly identical ADH and AHD activities with the possible exception of the high Km mitochondrial enzyme activity between days 3 and 6, and the low Km mitochondrial enzyme between days 28 and 32. Thus, it appears that differences in ethanol or acetaldehyde metabolism do not contribute significantly to the differential sensitivity to ethanol between young LS and SS mice or to the differential sensitivity between young and adult mice. PMID- 2310507 TI - Chronically administered morphine, circadian cyclicity, and intake of an alcoholic beverage. AB - Subsequent to 22 hr of deprivation of water, 40 male rats were given daily access to water and a sweetened ethanol solution for 2 hr each day for 24 days. Twenty of the rats had this opportunity to take fluids during the light-phase of the circadian cycle while the other twenty were given it during the dark. Prior to the 24 days, some rats (half of each group) were implanted subcutaneously with osmotic pumps giving them constant infusions of morphine (0.6 mg/kg/hr). Across daily sessions, all rats gradually increased their intakes of ethanol with the greatest increases among those having morphine and taking fluids during the light phase. The rats which drank during the dark gained more weight than the others and the most marked gains in weight were by those receiving no morphine. The data support the conclusion that some general disruption resulting from the schedule of presentation of fluids during the day qualifies as a setting condition for heightened intake of ethanol. PMID- 2310509 TI - Selective adsorption of apoferritin on immobilized Fe(III): demonstration of Fe(III) binding sites. AB - Immobilized metal ion affinity chromatography has been used to demonstrate and partially characterize Fe(III) binding sites on apoferritin. Binding of Fe(III) to these sites is influenced by pH, but not affected by high ionic strength. These results suggest that both ionic and coordinate covalent interactions are important in the formation of the Fe(III): apoferritin complex. This is, to our knowledge, the first demonstration of direct Fe(III) binding to apoferritin. Other immobilized metal ions, including Zn(II), Ni(II), Cu(II), Cr(III), Co(II), and Tb(III), displayed little or no adsorption of apoferritin. The analytical technique of immobilized metal ion affinity chromatography also shows great promise in the purification of apoferritin, ferritin, and other iron-binding proteins. PMID- 2310508 TI - Inhibition of testicular steroidogenesis in the neonatal rat following acute ethanol exposure. AB - We have previously reported detrimental effects of in utero ethanol exposure on testicular steroidogenic enzyme activity in newborn rats. It is now reported that in utero ethanol exposure during Day 12 of gestation through birth has no apparent morphological effect on the testes of Day 1 neonatal rats. It appears that the detrimental effects of ethanol on testicular steroidogenesis can be manifested at the biochemical level in the absence of morphological effects. However, it remained unknown as to whether acute exposure to ethanol would elicit similar biochemical effects as chronic ethanol exposure on testicular steroidogenesis. To test this possibility ethanol was injected at 0, 1, or 2 g/kg intraperitoneally (IP) into rats of various postnatal ages. Plasma ethanol and testosterone levels as well as testicular 17 alpha-hydroxylase and C17,20-lyase activities were measured. The results indicate that acute exposure to ethanol significantly (p less than 0.05) inhibits the catalytic activity of testicular 17 alpha-hydroxylase in the newborn rat testis. This inhibition was specific since the activity of testicular C17,20-lyase was not affected. In conjunction with the reduction in testicular enzyme activity, plasma testosterone levels were reduced to 30% of the control levels in newborn animals receiving ethanol. In older animals, i.e., postnatal Day 20 and 40 rats, plasma testosterone levels were reduced, but not significantly, following ethanol treatment. Furthermore, testicular enzyme activity was not significantly reduced following ethanol treatment in these same older animals. These results suggest that the newborn rat testis is especially sensitive to the effects of ethanol. PMID- 2310510 TI - Increasing cytostatic effects of ricin A chain and Staphylococcus aureus enterotoxin A through in vitro hydrophobization with fatty acid residues. AB - In order to impart an ability for receptor-independent transmembrane transfer to water-soluble proteins, it has been suggested that they be hydrophobized by lipid groups (fatty acids, etc.). To this end, systems of reversed micelles of surfactants in organic solvents were used as reaction media for protein modification. It was shown that after introduction of a hydrophobic anchor (stearic acid residue) the toxic effect of ricin A-chain (in the absence of B chain) on intact cells became very close to that of the native toxin. As a result of stearic acid acylation, the activity of Staphylococcal enterotoxin A increased by nearly 1.5-2 orders. The observed phenomena can be explained by receptor independent intracellular translocation of the hydrophobized toxins. PMID- 2310511 TI - A study of sulfite-tolerant yeasts from comminuted lamb products. AB - The sulfite tolerance of meat yeasts was shown to be determined by pH, sulfite concentration, substrate availability, and the composition of the preincubation medium. Acetaldehyde production by Candida norvegica was sulfite-induced and occurred during the exponential growth phase in sulfited (500 micrograms SO2 ml 1) lab lemco glucose broth cultures buffered at pH 5, 6, or 7. Growth at pH 4, however, was inhibited by sulfite. Acetaldehyde production occurred in sulfited medium containing fructose or ethanol but not lactate nor a range of other assimilable substrates. A non-acetaldehyde-producing yeast, Candida vini, grew in sulfited (500 micrograms SO2 ml-1) lab lemco broth containing glucose or lactate buffered at pH 6 or 7 but not at pH 4 or 5. PMID- 2310512 TI - The importance of adverse reactions in drug regulation. PMID- 2310513 TI - Could Swedish 'yellow cards' be substituted by E-coded summaries? AB - Case summaries of 2490 patients treated at the Department of Infectious Diseases, Danderyd Hospital, in 1986 were reviewed for discharge diagnoses where the International Classification of Disease (ICD) code indicated an adverse drug reaction (ADR) [E 939,9 in ICD 8]. Of 48 patients whose case summaries indicated an ADR, only 10 (21%) had been reported on 'yellow cards' to the Swedish Adverse Drug Reactions Advisory Committee. The Committee had also received from the same department 3 reports where the case summary lacked an ADR code. The information on drug treatment with respect to dosage, duration and treatment with concomitant drugs was not complete in the case summaries but sufficient for a preliminary evaluation of the suspected reactions in all but 4 of the cases. On the basis of these findings the authors do not reach an outright conclusion in favour of replacing the 'yellow card' system but the possible benefits of a system in which 'yellow cards' are supplemented by automatic referral of all case summaries containing an ICD code indicating an adverse drug reaction was judged sufficient to recommend and initiate a large field study. PMID- 2310514 TI - Solution structure of bacteriophage T4D and icosahedral capsid geometry visualized in freeze-fractured, deep-etched replicas. AB - The prolate icosahedral capsid geometry of wild type bacteriophage T4D has been determined by direct visualization of the triangular faces in stereoimages of transmission electron micrographs of phage particles. Bacteriophage T4 was prepared for transmission electron microscopy (TEM) following a protocol of freeze-fracturing, deep-etching (FDET) and replication by vertical deposition (80 degrees angle) of a thin platinum-carbon (Pt-C) metal layer of 1.01 nm. From direct statistical measurements of the ratio of the head length to width and of stereometric angles on T4 heads, we have estimated a Q number of 21. This confirms previous indirect studies on T4 and agrees with determinations on bacteriophage T2. Many of the structural features of T4 observed in FDET preparations differ significantly from those observed by classical negative staining methods for TEM imaging. Most important among the differences are the conformation of the baseplate (a closed rosebud) and the positioning of the tail fibers (retracted). The retracted position of the tail fibers in the FDET preparations has been confirmed by negatively staining phage previously fixed suspended in solution with 2% glutaraldehyde. The FDET protocols appear to reveal important structural features not seen in negative stained preparations. These have implications for bacteriophage T4 conformation in solution, viral assembly and phage conformation states prior to tail contraction and DNA ejection. PMID- 2310515 TI - The crystal structure of d(GTACGTAC) at 2.25 A resolution: are the A-DNA's always unwound approximately 10 degrees at the C-G steps? AB - The structure of the self-complementary octamer d(GTACGTAC) has been analyzed by a single crystal X-ray diffraction method at 2.25 A resolution. The crystallographic R factor was 0.184 for all 1233 reflections at this resolution. In spite of the alternating purine-pyrimidine sequence, d(GTACGTAC) adopts the A form conformation rather than the left-handed Z-form. The average helix twist and the mean rise per base pair are 32.1 degrees and 3.18 A, respectively. The d(GTACGTAC) helix is characterized by a wide open major groove and small base pair tilt (9.7 degrees). The partial unwinding of the helix is observed only at the central pyrimidine-purine C-G step, but not at the other pyrimidine-purine T A steps. Based on this study and six other X-ray studies, we propose a hypothesis that the A-DNA's are always unwound approximately 10 degrees at the C-G steps. Significant differences in base-pair stacking modes are seen between the purine pyrimidine step and the pyrimidine-purine step. All deoxyribose rings adopt the C3'-endo conformation. All backbone torsion angles fall into the range expected for the A-DNA form, except for the nucleotide G5, whose alpha and gamma torsion angles adopt the trans, trans conformation instead of the common gauche-, gauche+ conformation. PMID- 2310516 TI - Bh-DNA: variations of the poly[d(A)].poly[d(T)] structure within the framework of the fibre diffraction studies. AB - A refinement of the recent results for poly[d(A)].poly[d(T)] (Alexeev et al., J. Biomol. Struct. Dyn. 4,989 (1987)) involving additional parameters of the base pair structure and of the sugar-phosphate backbone expands the conformational potential of this polynucleotide of the B type to include the possibility of bifurcated hydrogen bonds of the kind recently discovered in crystalline deoxyoligonucleotide with lone d(A)n.d(T)n stretch (Nelson et al., Nature 330, 221 (1987)). Still, analysis of the available data and energy calculations do not seem to indicate that the bifurcated H-bonds are a crucial factor responsible for the anomalous structure of the d(A)n.d(T)n sequence. The unique structural properties of poly[d(A)].poly[d(T)] can hardly be explained without taking into account its interactions with the double-layer hydration spine in the minor groove. In view of the hydration mechanism stabilizing poly[d(A)].poly[d(T)] and of the polynucleotide's heteronomous prehistory (Arnott et al., Nucleic Acids Res. 11,4141 (1983)) we suggest that this B-type structure be called Bh. PMID- 2310517 TI - Different forms of the double helix in the pCpGpCpGpCpG crystals. AB - Four different crystal forms of the self-complementary oligonucleotide pCpGpCpGpCpG have been obtained. The space groups and the unit cell parameters of these crystals, as well as the location of the base-stacking reflections, indicate that the oligonucleotide is able to assume different double helical conformations that are dependent on the crystallization conditions. PMID- 2310518 TI - 1H NMR assignments and conformational analysis of the oligoribonucleotides CA, CAU, CAUG, ACAUG, and UCAUG: observation of pyrimidine H5-H1' long-range scalar couplings. AB - Conformational analysis and 1H NMR spectral assignments have been carried out using COSY and RELAY methods for a series of related oligoribonucleotides including two pentamers with 5'-dangling bases. Intraresidue long-range five bond scalar coupling was observed between pyrimidine H5 and H1' protons in the COSY-45 spectra and this feature was useful for both assignment purposes and conformational analysis. The ribose ring conformations were predominantly C3' endo with the C2'-endo population increasing at the 3'-terminus. The 5'-dangling bases were not stacked efficiently, exhibiting lower % C3'-endo values than their 3'-nearest neighbors. Backbone torsion angle population. beta t, gamma +, epsilon t, were determined using 1H-1H, 1H-31P, and 13C-31P coupling constants. From beta t and gamma + populations the U3-G4 step in CAUG was found to be less efficiently stacked than the C1-A2 and A2-U3 steps. This observation in solution is consistent with the fiber diffraction A-RNA model (S. Arnott, D.W.L. Hukins, S.D. Dover, W. Fuller and A.R. Hodgson, J. Mol. Biol. 81, 107-122, 1973) which also predicts poor stacking in a U-G dinucleotide. The epsilon t populations were greater than 65% for all C3'-O3' bonds and consistent with a right-handed A-RNA helix. PMID- 2310519 TI - Low frequency Raman spectra of Z-DNA. AB - We have performed a Raman study of the low frequency modes in three oligo- and polynucleotides in Z-conformation, and we compare the spectra of these samples to those of two polynucleotides in B-conformation. In Z-DNA we find 5 intrahelical modes below 200 cm-1, in addition to the interhelical mode near 30 cm-1 which is only observed in crystalline samples. The most prominent intrahelical mode has a frequency of about 105 cm-1, close to the frequency of the strongest intrahelical mode in A-and B-DNA. The sequence dependence of the frequency of this mode is considerably larger than for the same mode in B-DNA. The other modes are less pronounced, and their frequency variations with base sequence are within the experimental accuracy. PMID- 2310520 TI - Interaction of purine nucleotides with inert paramagnetic Cr(III) probes evaluated by NMR relaxation effects. Molecular mechanics calculations on Cr(III) and Co(III) polyphosphate complexes. AB - The 1H NMR relaxation effects produced by paramagnetic Cr(III) complexes on nucleoside 5'-mono- and -triphosphates in D2O solution at pH' = 3 were measured. The paramagnetic probes were [Cr(III)(H2O)6]3+, [Cr(III)(H2O)3(HATP)], [Cr(III)(H2O)3(HCTP)] and [Cr(III)(H2O)3(UTP)-, while the matrix nucleotides (0.1 M) were H2AMP, HIMP-, and H2ATP2-. For the aromatic base protons, the ratios of the transverse to longitudinal paramagnetic relaxation rates (R2p/R1p) for the [Cr(III)(H2O)6]3+/H2ATP2-, [Cr(III)(H2O)3(HATP)]/H2ATP2-, [Cr(III)(H2O)3(HCTP)]/H2ATP2 and [Cr(III)(H2O)3(UTP)]-/H2ATP2 systems were below 2.33 so the dipolar term predominates. For a given nucleotide, R1p for the purine H(8) signal was larger than for the H(2) signal with the [Cr(III)(H2O)6]3+ probe, while R1p for the H(2) signal was larger with all the other Cr(III) probes. Molecular mechanics computations on the [Cr(III)(H2O)4(HPP)(alpha,beta)], [Cr(III)(NH3)4(HPP)(alpha,beta)], [Co(III)(NH3)3(H2PPP)(alpha,beta,gamma)] and [Co(III)(NH3)4(HPP)(alpha,beta)] complexes gave calculated energy-minimized geometries in good agreement with those reported in crystal structures. The molecular mechanics force constants found were then used to calculate the geometry of the inner sphere [Cr(III)(H2O)6]3+ and [Cr(III)(H2O)3(HATP)(alpha,beta,gamma)] complexes as well as the structures of the outer sphere [Cr(III)(H2O)6]3(+)-(H2AMP) and [Cr(III)(H2O)6]-(HIMP)- species. The gas-phase structure of the [Cr(III)(H2O)3(HATP)(alpha,beta,gamma)] complex shows the existence of a hydrogen bond interaction between a water ligand and the adenine N(7)(O...N = 2.82 A). The structure is also stabilized by intramolecular hydrogen bonds involving the -O(2')H group and the adenine N(3) (O...N = 2.80 A) as well as phosphate oxygen atoms and a water molecule (O...O = 2.47 A). The metal center has an almost regular octahedral coordination geometry. The structures of the two outer-sphere species reveal that the phosphate group interacts strongly with the hexa-aquochromium probe. In both complexes, the nucleotides have a similar "anti" conformation around the N(9)-C(1') glycosidic bond. However, a very important difference characterizes the two structures. For the (HIMP)- complex, strong hydrogen bond interactions exist between one and two water ligands and the inosine N(7) and O(6) atoms, respectively (O...O = 2.63 A; O...N = 2.72, 2.70 A). For the H2AMP complex, the [Cr(III)(H2O)6]3+ cation does not interact with N(7) since it is far from the purine system. Hydrogen bonds occur between water ligands and phosphate oxygens. The Cr-H(8) and Cr-H(2) distances revealed by the energy-minimized geometries for the two outer sphere species were used to calculate the R1p values for the H(8) and H(2) signals for comparison with the observed R1p values: 0.92(c), 1.04(ob) (H(8)) and 0.06(c), 0.35(ob) (H(2)) for H2AMP; and 3.76(c), 4.53(ob) (H(8)) and 0.16(c), 0.77(ob) s-1 (H(2)) for HIMP-.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2310521 TI - Parallel double helices of DNA. Conformational analysis of regular helices with the second order symmetry axis. AB - We have performed a conformational analysis of DNA double helices with parallel directed backbone strands connected with the second order symmetry axis being at the same time the helix axis. The calculations were made for homopolymers poly(dA).poly(dA), poly(dC).poly(dC), poly(dG) poly(dG), and poly(dT).poly(dT). All possible variants of hydrogen bonding of base pairs of the same name were studied for each polymer. The maps of backbone chain geometrical existence were constructed. Conformational and helical parameters corresponding to local minima of conformational energy of "parallel" DNA helices, calculated at atom-atom approximation, were determined. The dependence of conformational energy on the base pair and on the hydrogen bond type was analysed. Two major conformational advantageous for "parallel" DNA's do not depend much on the hydrogen-bonded base pair type were indicated. One of them coincided with the conformational region typical for "antiparallel" DNA, in particular for the B-form DNA. Conformational energy of "parallel" DNA depends on the base pair type and for the most part is similar to the conformational energy of "antiparallel" B-DNA. PMID- 2310522 TI - Conformational features of DNA containing a cis-syn photodimer. AB - In an effort to understand the conformational and structural changes in DNA brought about by thymine photodimer, computer modeling and molecular mechanics energy calculations were performed on DNA hexamer and dodecamer duplexes containing a cis-syn photodimer. The conformation of the crystal structure of the cyanoethyl phosphate ester of the thymine dimer (Hruska et al., Biopolymers 25, 1399-1417 (1986)) was used in modeling the photodimer portion. Various starting conformations were used in the modeling procedure and the structures were minimized both retaining and later relaxing the crystallographic geometry of the cyclobutane ring. The results indicate that most of the deformation is restricted to the thymine dimer region, and that the conformational changes decrease rapidly on either side of the region containing the photodimer. The structural changes brought about by the introduction of the photodimer can be accommodated within six base paired duplex without significant bend in the DNA. More conformational changes are observed on the 5'-side of the photodimer than on the 3'-side. The conformational features, such as backbone torsion angles and sugar puckers, of the energy minimized structures are discussed in the context of the solution structures determined by NMR on a series of oligomers containing photodimers (Rycyna et al., Biochemistry 27, 3152-3163 (1988)). PMID- 2310523 TI - Base pair opening pathways in B-DNA. AB - Molecular modeling is used to study the opening pathways of bases within a B-DNA oligomer. It is demonstrated that many open states are possible for a single base pair, although a preference for opening towards the major groove of the double helix is found. In addition we show that opening is strongly influenced by the nature of the base involved and is also coupled in many cases to DNA bending. PMID- 2310524 TI - A refined calculation of the solution dimensions of the complex between gene 32 protein and single stranded DNA based on estimates of the bending persistence length. AB - The rotation diffusion coefficient of a complex of GP32, the single stranded DNA binding protein of the bacteriophage T4, with a single stranded DNA fragment with about 270 bases was determined to obtain further information on the flexibility of this particle. The rotation diffusion of these molecules is used as a sensitive measure of the flexibility of different DNA protein complexes. Using the theory of Hagerman and Zimm (Biopolymers 20, 1481 (1981)) and assuming a bending persistence length of about 35 nanometer it can be shown that the axial increment for GP32 complexes with single stranded DNA is close to 0.5 nm per base. The value for the bending persistence length is in agreement with values found for much larger DNA protein complexes using light scattering experiments. This value for the persistence length also implies that the complex is thin. The radius is estimated to be around 1.7 nm, which shows a moderate degree of hydration. With this set of parameters we can describe all the hydrodynamic experiments on GP32 complexes from 76 to more than 7000 bases obtained using electric birefringence, quasi-elastic light scattering and sedimentation experiments performed in our group over the last few years. PMID- 2310525 TI - Thermodynamic modeling of internal equilibria involved in the activation of trypsinogen. AB - The effect of activating dipeptides, sequentially homologous to the Ile16-Val17N terminus of bovine beta-trypsin (beta-trypsin), on equilibria involved in the binding of strong ligands (i.e., n-butylamine, the bovine basic pancreatic trypsin inhibitor (Kunitz-type inhibitor; BPTI) and the porcine pancreatic secretory trypsin inhibitor (Kazal-type inhibitor, type I; PSTI)) to bovine trypsinogen (trypsinogen) was investigated at pH 5.51 (I = 0.1 M) and T = 21.0 +/ 0.5 degrees C; under the same experimental conditions, thermodynamics for the binding of strong ligands to beta-trypsin was also obtained. The equilibria involved in the binding of activating dipeptides and/or inhibitors to beta trypsin and to its zymogen are described according to an induced-fit formalism, taking into account ligand-linked interaction(s) between different functional and structural domains of the (pro)enzyme possibly involved in the trypsinogen-to beta-trypsin activation pathway. The analysis of data is focussed on parameters describing interactions between the so-called Ile-Val pocket (where the Ile16 Val17 N-terminus of beta-trypsin or activating dipeptides bind) and the primary and/or secondary recognition subsite(s) (where strong ligands associate) present in the (pro)enzyme. Such an analysis allows to dissect the contributions due to the primary recognition subsite, where small mono-functional ligands (e.g., n butylamine) bind, from those of the secondary subsite(s), which are additional recognition clefts for macromolecular inhibitors (e.g., BPTI and PSTI). PMID- 2310526 TI - Distribution of charged residues stabilizes individual helices in myoglobins. AB - The effect of the distribution of charged residues on stability of alpha helices in isolated peptides and in globular proteins exemplified by myoglobins from 62 different species is discussed. A highly simplified set of rules is used to account for the interaction of charged groups with the dipole of an alpha helix. Only the position and sign of a charge with respect to the center of the helix and its ability to participate in intrahelical salt bridges determine its effect. These rules lead to a linear correlation between the helicity in variant C peptide helices from RNAse and the extent to which the charge distribution opposes the helix dipole. Of the sample of 496 helices in the myoglobins studied, 456 exhibit arrangements of charges which oppose the effective dipole moment of the helix according to this calculation. A number of variants occur which leave the backbone moment of helices A-D unchanged, or even add to it. However no such variants exist in the sequences of helices E-H. We suggest that the E, F, G and H helices in myoglobins which show the strongest reversal of the helix dipole participate in the structures of early intermediates in folding of the chain. Stable helix structures should be more likely to occur in these isolated sequences also, and introduction of charge alterations in helices E to H should affect the initial refolding rate of mutant myoglobins. PMID- 2310528 TI - Residential care. Home from home. PMID- 2310527 TI - Secondary structure of the human membrane-associated folate binding protein using a joint prediction approach. AB - The secondary structures of the human membrane-associated folate binding protein (FBP) and bovine soluble FBP are assessed by a joint prediction approach that combines neural network models, information theory, homology modeling and the Chou-Fasman methods. Two new profile maps are used to characterize the non regular secondary structure and to assist in assigning buried and exposed parts of secondary structure: (i) the loop potential profile and (ii) the long range contact profile. Approximately half of human FBP is predicted to form regular secondary structure (alpha-helices-35% or beta-sheets - 12%, excluding the transmembrane helices) and the rest is predicted to form coil, turns or loops. The bovine milk soluble FBP is predicted to have a similar secondary structure as expected because of the high degree of homology between the FBP's. Discriminant analysis predicts two transmembrane segments for the human FBP sequence, one at the amino terminus (a leader sequence) and the other at the carboxy terminus. These predicted transmembrane domains are absent in the bovine milk soluble FBP, further supporting these predictions. The present set of secondary structural predictions for human FBP is obtained by 'consensus' to aid in modeling the super secondary structure of the protein. PMID- 2310529 TI - Lifting: taking the strain. PMID- 2310530 TI - Community care: bill of change. PMID- 2310532 TI - Day hospital care. PMID- 2310531 TI - Osteoporosis: bone disease in the elderly. PMID- 2310533 TI - The art of growing old. PMID- 2310534 TI - What can the matter be? PMID- 2310535 TI - Direct phase determination for the molecular envelope of tryptophanyl-tRNA synthetase from Bacillus stearothermophilus by X-ray contrast variation. AB - Monoclinic crystals of Bacillus stearothermophilus tryptophanyl-tRNA synthetase grown in the presence of substrate tryptophan (space group P2(1)) display evidence of a low-resolution trigonal space group (P321). The origin and averaging transformations for the local 32 point group of this unusually clear sixfold non-crystallographic symmetry may be inferred without prior estimation of the electron density. This local symmetry was exploited in conjunction with solvent density contrast variation to determine the shape of the molecular envelope. X-ray intensities measured from crystals equilibrated in mother liquors of three different electron densities were used to estimate three parameters for each reflection: the modulus of the envelope transform, [Gh]; and components, Xh and Yh, relative to Gh, of the structure-factor vector for the transform of intramolecular density fluctuations. The moduli ([Gh]) behave somewhat like structure-factor amplitudes from small-molecule crystals, and estimation of their unknown phases was successfully carried out by statistical direct methods. Reflections to 18 A resolution, which obey rather well the symmetry of space group P321, were merged to produce an asymmetric unit in that space group. [Gh] values for the 34 strongest of these were phased using the small-molecule direct methods package MITHRIL [Gilmore (1984). J. Appl Cryst. 17, 42-46]. The best phase set was expanded back to the P2(1) lattice and negative density was truncated to generate initial phases for all reflections to 18 A resolution. Phase refinement by iterative imposition of the local 32 symmetry produced an envelope with convincing features consistent with known properties of the enzyme. The envelope implies that the tryptophanyl-tRNA synthetase dimer is an elongated structure with an axial ratio of about 4:1, in which the monomers have two distinct domains of unequal size. The smaller of these occurs at the dimer interface, and resembles the nucleotide binding portion of the tyrosyl-tRNA synthetase. It may therefore contain the amino-terminal one hundred or so residues, including all three cysteines, previously suggested to comprise a nucleotide-binding domain in the tryptophanyl enzyme. A purely crystallographic test of the overall features of this envelope was carried out by transporting it to a tetragonal crystal form of the same protein in which the asymmetric unit is a monomer. The small domain fits snugly inside three mercury and one gold heavy atom binding sites for this crystal form; and symmetry-related molecules provide excellent, but very different, lattice contacts in nearly all directions. PMID- 2310536 TI - [Are legal sanctions for improving traffic safety adequate?]. AB - Referring to the field of traffic legislation the author examines the different possibilities to improve the safety on the road, within the corresponding range of summary offence and criminal law; (1) As far as the rules of conduct are concerned he demands a uniform threshold value of at least 0.8% for blood alcohol within the limits of the German penal code Sections 315 c I, 316. He rejects the plan to introduce a criminal offence of considerable speeding if imminent danger is provoked. (2) On the level of sanctions the traditional measures of traffic legislation are to be supplied sensibly by supplementary training courses concerning alcohol abuse. The legal instruments of (temporary) suspension of a person's driving license on the part of criminal jurisdiction or public authorities ought to be utilized on a larger scale. The (Flensburg) repeated perpetration point system is to be improved with regard to special preventive measures. (3) To increase the risk of being caught the control of the traffic by the police is to be intensified--especially through a larger application of technical means. (4) The extension of the instruments of traffic legislation to immediate measures by the police--preliminary or "mini" suspension of a person's driving license by resort to preventive rights by the police?--meets with constitutional or legal scruples. PMID- 2310537 TI - [New methods of pharmacokinetic evaluation of alcohol and its metabolites in female and male probands]. AB - The Pharmacokinetics of ethanol and its metabolites were examined in 10 young healthy women and men after 1-hr intravenous ethanol application of 7.8 mmol/kg body weight. Therefore, a new pharmacokinetic model takes into account Michaelis Menten-elimination kinetics of ethanol as well as kinetics of acetaldehyde and acetate, which are defined by first order processes. The metabolite-model adequately describes the ethanol and acetate concentration courses. In fact, the observed ethanol concentrations are so close to the model-predicted values, that the metabolite-model allows an evaluation of half-life-times of acetaldehyde and acetate. The analyses of ethanol infusion studies showed, that there are no sex differences in parameters of ethanol elimination: Maximal elimination velocity Vmax was 3.41 +/- 0.61 mmol/l.h in females and 3.98 +/- 0.69 mmol/l.h in males. Michaelis-Menten-constant kM was 1.49 +/- 0.44 mmol/l and 1.69 +/- 0.88 mmol/l, respectively. In the female group, the volume of distribution of ethanol V1 was with 38.4 +/- 5.01 significant smaller than in males with 50.5 +/- 3.51. In conclusion, the new metabolite-model can be used as a basis for the investigation of the entire alcohol metabolism. PMID- 2310538 TI - [Alcohol and street traffic (critical comments from the legal and traffic medicine viewpoint)]. AB - 1. Our official traffic statistics in general and in regard to the problem "alcohol and road traffic security" is not reliable enough. It contains too many unaccounted factors, so that an objective reorganisation and supplement is badly needed. The present statistics is not suited to show the real dimension and the actual danger of the effects of "alcohol in traffic", especially in connection with relatively low blood-alcohol-concentration. 2. In connection with the problem "alcohol and road traffic" the Federal Republic of Germany is able to develop, by way of law, significant epidemiological research, which, so far, has been neglected. 3. Danger and frequency of low and high blood-alcohol concentration in road traffic participants are collectively in inverse ratio: The larger group of the less dangerous road traffic participants with low blood alcohol-concentration does not necessarily cause less damage, than the smaller group of the more dangerous ones with high blood-alcohol-concentration. 4. From the legal and traffic medical point of view the reaching and exceeding of the abstract promille limit of 0.8 shoudl be considered a violation within the meaning of penal law and should be connected with the loss of the driver's license. This was put up for discussion by Spiegel (1989). Such a legal measure would lead to a consequent and successful general and specific prevention. There should be initiated supportive side effects as for example discrimination of the drunken driver and permanent education concerning the effects of alcohol on traffic safety. 5. It seems reasonable to set the limit as low as possible, however, only if there is an sufficient police control to make it effective. 6. The concept "absolute driving incapability" has an extreme confidential value and will surely not result in any disadvantages, however, its preventive reaction is not sufficient. There is no need for this concept any more, if an abstract danger limit is connected with appropriate sanctions for an offense and with the withdrawal of the driver's license. 7. In many cases it is not without problem to assess evidence for characterizing a precise (relative) driving incapability. The valuation of driving incapability could be restricted to a blood-alcohol concentration range between the threshold of 0.3 promille and the danger limit of 0.8 promille, if point 4. were put into action. The fact that low blood-alcohol concentration leads to an increased frequency of minor mistakes, while relative high blood-alcohol-concentration is characterized by typical kinds of mistakes, makes the judgement of driving incapability more difficult. PMID- 2310539 TI - [1989 Senator Lothar Danner Gold Medal for Prof. Dr. phil. Werner Winkler]. PMID- 2310540 TI - Thermoelectric enzyme sensor for measuring blood glucose. AB - A new calorimetric sensor has been developed which employs a thin-film thermopile in association with an immobilized enzyme. The thermopile detects the minute temperature rise that occurs when a specific chemical substrate is catalyzed by the enzyme. A prototype sensor is described which generates an equivalent proportional voltage response to glucose concentrations present in either buffer solution or blood. These sensors have remained useful for up to 18 days when operated intermittently for measuring glucose in buffer solutions, or for up to 4 days when operated continuously. When implanted inside cardiovascular shunts on anesthetized dogs, the sensors responded appropriately to changes in the blood glucose concentration. PMID- 2310541 TI - Development of a potentially wearable glucose sensor for patients with diabetes mellitus: design and in-vitro evaluation. AB - A potentially wearable glucose sensor was developed, consisting of an oxygen electrode as detector and a dynamic enzyme perfusion system as selector. The selector is a hollow fibre, which can be placed subcutaneously and dialyses glucose from tissue fluid. In this design the problems of enzyme instability and oxygen limitation might be circumvented. The sensor measures glucose reliably for over two weeks, provided a new 10 ml syringe containing a glucose oxidase solution is connected to the system each day. PMID- 2310542 TI - Comparative ultrastructure of subsurface cisternae in inner and outer hair cells of the guinea pig cochlea. AB - The subsurface cisternal systems of outer hair cells (OHCs) from different cochlear regions have been compared with the subsurface cisternal system of inner hair cells. Three main observations have been made: (1) the number of cisternal layers, when there is more than one present, is reduced along the length of an individual outer hair cell; (2) basal outer hair cells may have only one fenestrated cisternal layer; and (3) the inner hair cells possess a lateral cistern and associated pillar and filament complexes which are very similar to those of some basal OHCs. These observations are discussed in relation to hypotheses regarding the role of these structures in hair cell motility. PMID- 2310543 TI - The effect of adenylate cyclase stimulation on endocochlear potential in the guinea pig. AB - Forskolin, a diterpene extracted from Coleus forskohlii, is potentially an important tool for studying the modulation of ionic currents by cAMP because it stimulates adenylate cyclase in a variety of cells. We studied the effect of forskolin on cochlear potentials and found that its perfusion of the scala vestibuli (SV) to a concentration more than 10(-5) M and the scala tympani (ST) to more than 10(-4) M produced a reversible elevation of the endocochlear potential (EP) in a dose-dependent manner. The cochlear microphonics recorded simultaneously with the EP was not depressed during the EP elevation. A large negative EP was induced by anoxia following the SV perfusion with forskolin (2 X 10(-4) M). The results suggest that the EP elevation produced by forskolin does not result from the decrease in the negative component of EP but from the increase in the positive component of EP. PMID- 2310544 TI - Laser light transmission and laser Doppler blood flow measurements on the human, rat and guinea pig cochlea. AB - In order to test the applicability of laser-Doppler flowmetry in monitoring cochlear blood flow clinically, the thickness and the helium-neon laser light transmission of specimens of human, rat and guinea pig promontory bone and human skin were determined. Furthermore, comparative laser-Doppler measurements were taken from the promontory in patients, rats and guinea pigs. Due to the different thicknesses of the promontory bone in different species, the light transmission was found to be considerably higher for the animal cochlea (rat, 15%; guinea pig, 6.6%) than the human cochlea (1.7%). However, a clearly higher laser-Doppler signal was recorded from both the human and the rat cochleas as compared with the guinea pig. The relative laser light attenuation by the human skin specimens corresponded to that of the human promontory bone. The findings are discussed with regard to the suitability of the laser-Doppler method for blood flow measurements in the human cochlea. PMID- 2310545 TI - Frequency variation in spontaneous sound emissions from guinea pig and human ears. AB - Spontaneous acoustic emissions were recorded from 7 of 15 human ears at frequencies between 900 and 4000 Hz and just above 1000 Hz in a guinea pig. The constancy or changes in the frequency composition of these emissions is of particular interest in the light of current models which implicate outer hair cell activity in their generation. In our present study, most emissions underwent continuous fluctuations in frequency over a bandwidth of 0.5-10 Hz in humans and more than 20 Hz in a young guinea pig. Jumps in frequency of emission by as much as 20 Hz occurred during test sessions in some of the human ears. Changes in emission frequency were also observed during suppression by an externally delivered tone. The frequency of the emissions at successive test sessions also varied in some human ears and in the guinea pig between the ages of 6 and 9 weeks. The guinea pig emission also underwent an increase of 50 Hz in frequency and a reduction of 25 dB in level during recovery from anaesthesia. Neely's model for the role of hair cells in the generation of spontaneous emissions suggests that changes in hair cell conductance could influence the frequency of spontaneous oscillation. The small, but continuous changes in spontaneous emission frequency seen in all ears may reflect changes in conductance at the hair cell level due to synaptic and transducer channel activity. PMID- 2310546 TI - The problem of obtaining reproducible quantitative data of the olivocochlear pathway as exemplified in the guinea pig. AB - We have tried to quantify the number of efferent neurons comprising the olivocochlear bundle in the guinea pig by using the retrogradely transported fluorescent dye, true blue. The dye was injected into numerous regions of the cochlea for various distances. The data from 14 complete experiments have been evaluated. The majority of the labelled cells were found ipsilaterally, with the lateral superior olive containing 59.2% and showing cochleotopicity. Of the 28.9% found contralaterally, the nucleus of the ventral lateral lemniscus had 16.9%, and the trapezoid body nucleus 8.0%, differing significantly from the other nuclei of the superior olivary complex. Although the distribution of the labelling was consistent, there was great variability in actual numbers. Calculations based on cell density showed no differences along the length of the basilar membrane, and resulted in a total of around 2500 efferent neurones. This figure agrees closely with the maximum counts found by other workers. However, the cause of the individual variability remains unanswered. PMID- 2310547 TI - Latencies of eighth nerve fibre responses with respect to their relative contribution to the compound action potential in the guinea pig. AB - We present a study of the latencies of click-evoked post-stimulus time histograms (PSTHs) in the guinea pig in the context of the auditory nerve fibre's contribution to the compound action potential (CAP) recorded at the round window. The latencies of the dominant PSTH peak were studied as a function of relevant physiological fibre properties, in particular the characteristic frequency (CF) and the spontaneous discharge rate (SR). We found that high-SR fibres have shorter latencies than low-SR fibres. These findings are discussed in the context of correlation between synaptic morphology and SR as described in the literature. The PSTH latency as a function of CF is described separately for low- and high-CF fibres for each of the two SR subgroups. Finally, we discuss to what extent the various subgroups of fibres contribute to the N1 peak of the CAP, the most commonly studied component. PMID- 2310548 TI - The effect of taurine supplementation on the ototoxicity of neomycin in guinea pigs. AB - Experiments have been performed to examine the effects of taurine supplementation on the ototoxicity of neomycin. It was found that concurrent administration of taurine and neomycin produced a greater degree of ototoxicity, as evidenced by increases in hearing thresholds, than with neomycin alone. The results are discussed in light of a recently proposed mechanism of aminoglycoside ototoxicity. PMID- 2310549 TI - A cytoskeletal spring for the control of cell shape in outer hair cells isolated from the guinea pig cochlea. AB - A two-dimensional cortical cytoskeletal lattice associated with the lateral plasma membranes of mammalian outer hair cells maintains cell shape and provides a restoring force to oppose active changes in cell length. The lattice is composed of two morphologically distinct filaments which are arranged to reinforce the cell circumferentially whilst allowing limited changes in cell length and diameter. This function can only be fulfilled if intracellular pressure is high enough to put the lattice under tension. PMID- 2310550 TI - Central diplacusis. AB - Although diplacusis is usually indicative of cochlear pathology, to our knowledge causes in the central nervous system ("central diplacusis") have not been mentioned in the available literature. A case of central diplacusis involving a lesion in the posterior thalamus is now reported that resulted in diplacusis binauralis. A neuro-audiological explanation is offered to explain this phenomenon. Presumably, a lesion at the geniculate-collicular level, where pain and tactile impulses are interrelated with auditory, visual and olfactory ones, leads to the phenomenon perceived. PMID- 2310551 TI - Morphologically specific vestibular hair cell degeneration in the jerker mouse mutant. AB - The vestibular organs in homozygote (je/je) and heterozygote (je/+) 1- to 12 month-old jerker mouse mutants were analyzed morphologically using light microscopy and transmission and scanning electron microscopy. The pathological changes were initially confined to the surface structure of predominantly type I hair cells. The latter cells showed disintegration of the cuticular plate, disarray of stereocilia and finally fusion of sensory hairs. The hair cells were then expelled into the endolymphatic space. A notable finding was that most expelled hair cells still showed a rather normal ultrastructure of their cytoplasm and nuclei. The morphological type of pathology was the same in je/je and je/+ mutants. However, in je/je animals the degeneration occurred within 1-3 months after birth, whereas in je/+ mutants a slowly progressive degeneration lasted for up to 1 year of age or even more. The degeneration was more extensive in the two maculae than in the three cristae ampullares. PMID- 2310552 TI - Cartilage in the bony portion of the eustachian tube. AB - The distribution of cartilage in the bony section of the eustachian tube was studied by examining histological serial sections of 50 temporal bones of infants and adults. When cartilage was found to be present in the bony segments of the eustachian tube, its cross-sectional area was measured. Cartilage was seen in the isthmic region in all specimens. In the post-isthmic region it was present in all of the specimens taken from infants and in 92.3% of the adult specimens. In the pretympanic region cartilage was found in 34.6% of the infants' eustachian tubes and in 25% of the adults'. The results indicate that cartilage is also present in the bony part of the eustachian tube at all ages but diminishes in frequency the more the eustachian tube approaches the middle ear. PMID- 2310553 TI - Viscoelastic properties of middle ear effusions from pediatric otitis media with effusion and their relation to gross appearance. AB - The viscosity and the elasticity were measured in 146 individual middle ear effusions (MEEs) from 93 children with otitis media with effusion (OME). The effusions were classified into serous or mucoid type by their macroscopic appearance. The distribution of elasticity showed two peaks, corresponding to the peaks of serous and mucoid types of effusions. There were a small number of effusions in the intermediate range of elasticity, where the effusions were most effectively transported by the cilia. These findings suggests that the MEEs of pediatric OME are accumulations of rheologically suboptimal fluid in the middle ear cavity. PMID- 2310554 TI - Auditory brainstem response thresholds in a mouse mutant with selective outer hair cell loss. AB - Mutant animals with a particular type of cochlear pathology are an excellent model for studying the functional role of various cells of the cochlea. In homozygous WV/WV mutant mice we found a selective loss of outer hair cells as a constant defect with no progressive degeneration of the organ of Corti. The mice were followed throughout their lives and exhibited auditory brainstem responses that were elevated to about 50 dB SPL as compared to normal control animals. Sequential temporal bone studies showed that there was a selective loss of outer hair cells throughout the entire cochlea as seen in surface preparations. The inner hair cells were present in normal numbers and appeared to be essentially normal. PMID- 2310555 TI - Gamma-motoneurone discharge patterns during fictive locomotion in the decerebrate cat. AB - Triceps surae gamma-motoneurones were recorded during fictive locomotion in the paralysed high decerebrate cat. Two distinctive patterns of discharge were observed which were similar to those reported for static and dynamic gamma motoneurones during locomotion in the same preparation, but without paralysis (Murphy, Stein & Taylor, 1984). These results suggest that movement-related afferent feedback is not essential for the generation of the basic patterns of static and dynamic gamma-motoneurone activity during locomotion. The results are discussed in relation to the generation of alpha and gamma locomotor rhythms. PMID- 2310556 TI - Pulmonary shunting by the bronchial artery in the anaesthetized horse. AB - In the quietly standing horse the bronchial arterial blood flow is low, 0.1-0.2% of the pulmonary arterial flow. In horses anaesthetized with halothane, the bronchial arterial flow is reduced by a greater fraction than that in the pulmonary artery. Thus the shunting through the bronchial circulation is decreased about 3-fold by anaesthesia, and cannot, therefore, contribute significantly to the increased alveolar-arterial gradient seen in dorsal recumbency. The results indicate bronchial vasoconstriction under anaesthesia. PMID- 2310557 TI - Thixotropy in frog single muscle fibres. AB - The thixotropic properties of single muscle fibres have been investigated. The effect is larger than in whole muscle and although the time course of stiffness recovery is generally similar, there is an indication that two phases may be involved. Rigor, induced chemically, eliminates thixotropic behaviour. PMID- 2310558 TI - Direct and indirect contractile responses of the human vas deferens and actions of noradrenaline and of calcium antagonists. AB - Contractile responses of the isolated human vas deferens, obtained from vasectomy operations, were measured. Large single electrical shocks gave a twitch response with short latency (0.36 s) which was insensitive to prazosin (5 microM) or TTX (0.2 microM) and was thus identified as due to direct muscle stimulation. A train of 100 low intensity shocks gave a response with a longer latency (1.9 s) which was substantially sensitive to both prazosin and TTX; we assume this response is dominated by an indirect nerve-induced contraction. Relaxations, presumably caused by activation of circular muscle, were recorded from regions of some preparations both by direct and indirect stimulation. Noradrenaline (10-20 microM) induced a tonic contracture, spontaneous contractions and a large potentiation of the response to direct stimulation--but not to indirect stimulation implying a strong presynaptic inhibition. Noradrenaline also speeded the relaxation from contractions. Verapamil (1-100 microM) and nifedipine had no effect on the direct responses but verapamil (10 microM) inhibited the indirect response. Calcium removal prevented most, and 5 mM-EDTA all, of the direct response. However, even with EDTA, noradrenaline was able to support spontaneous and stimulus-induced contractions. Thus contraction of the vas, though sustained by external calcium, does not appear to directly depend on it. PMID- 2310559 TI - Fluid absorption from the rumen during rehydration in sheep. AB - Water movements across the rumen wall were studied during rehydration in four fistulated sheep. The animals were dehydrated for 48 h which increased total plasma protein, plasma osmolality, plasma Na+, arginine vasopressin and plasma renin activity. Two series of experiments were performed: Expt I with no food available during rehydration, and Expt II where the animals were fed hay. On the rehydration day, a fluid marker (cobalt-EDTA) was administered into the rumen. To avoid water outflow from the rumen a stopper was inserted into the reticulo omasal orifice. When the animals were provided with water they immediately drank 9 l. The water offered contained the same marker concentration (Co2+) as in the rumen liquid. In Expt I, Co2+ concentration increased after drinking, and remained elevated until the stopper was removed. The highest value was obtained after 20 min, and this corresponded to at least a 11 water absorption in individual animals. In Expt II, the sheep immediately started to eat following drinking and the inflow of saliva caused a dilution of the marker. Plasma osmolality and Na+ concentration decreased in both experiments indicating that water absorption occurred in both experiments. Removal of the stopper did not cause any significant changes in the parameters measured. Vasopressin concentration fell immediately on the sight of water, and then continued to decrease. It is concluded that in the sheep, voluntary drinking is followed by an immediate and substantial absorption of water from the rumen. PMID- 2310560 TI - Water and sodium movements across the ruminal epithelium in fed and food-deprived sheep. AB - Fluid and electrolyte movements across the ruminal epithelium of sheep were studied using the temporarily isolated rumen technique. The sheep were all subjected to the following treatments: (1) fed sheep (fed twice daily), after rumen emptying, received rumen contents from a fed sheep; (2) food-deprived sheep (two meals were omitted), after rumen emptying, received rumen contents from a food-deprived sheep; (3) fed sheep, after rumen emptying, received rumen contents from a food-deprived sheep; and (4) food-deprived sheep, after rumen emptying, received rumen contents from a fed sheep. Food deprivation led to an increased Na concentration of the rumen fluid while K and Cl concentrations, as well as osmolality, decreased. Plasma Na and osmolality decreased. During the 40 min after the rumen contents were exchanged no net movements of water occurred. Then the sheep were given an intraruminal load of saline which gave rise to a significant net absorption of fluid from the rumens of those sheep which had received rumen contents from fed sheep. The change in composition of the rumen contents after food deprivation impaired the absorption of Na and water from the rumen. Furthermore food deprivation reduced the Na absorptive function of the ruminal epithelium, but not the water permeability. PMID- 2310561 TI - Contribution of lymph formation in the popliteal node to efferent lymph flow following stimulation of the sympathetic chain in the sheep. AB - Lymph flow and contraction frequency were measured in popliteal efferent lymphatics. Stimulation of the ipsilateral sympathetic chain resulted in an approximate threefold increase in lymph flow, while contraction frequency increased 28% (n = 6). Occlusion of the metatarsal afferent lymphatics with a pneumatic cuff reduced efferent flow from 18 to 4 microliters/min after 25 min (n = 5), indicating that approximately 80% of popliteal efferent lymph is derived from the foot. After occlusion of the afferent lymphatics, sympathetic stimulation failed to increase efferent lymph flow significantly, while efferent contraction frequency still showed a significant rise. It is concluded that lymph formation in the popliteal node does not contribute to the rise in efferent lymph flow following sympathetic stimulation. PMID- 2310562 TI - The effects of lower body negative pressure on baroreceptor responses in humans. AB - In healthy human subjects the immediate responses of pulse interval and the steady-state responses of arterial blood pressure and cardiac output to changes in carotid sinus transmural pressure were determined before and during the application of a subatmospheric pressure to the lower part of the body. Increases in carotid sinus transmural pressure, effected by applications of subatmospheric pressure to the neck (neck suction) resulted in prolongation of pulse interval and decrease in blood pressure; opposite responses were obtained to application of a positive pressure (neck pressure). Application of lower body negative pressure resulted in a decrease in pulse interval (heart rate increase) but little change in blood pressure. During lower body negative pressure, the responses of pulse interval to neck pressure were reduced but those to neck suction were unaffected; the responses of blood pressure to neck suction were enhanced but those to neck pressure were unaffected. From experiments in which cardiac output was also determined, it was seen that lower body negative pressure reduced cardiac output, increased calculated total body vascular resistance and augmented the resistance response to neck suction although not to neck pressure. These results are compatible with the view that application of lower body negative pressure does not change the sensitivity of the baroreceptor reflex and that the changes in the responses are due to non-linearities of the stimulus response curves. PMID- 2310563 TI - Sequences of the CyIIIa actin gene regulatory domain bound specifically by sea urchin embryo nuclear proteins. AB - Expression of the CyIIIa cytoskeletal actin gene is a marker of differential gene activation in the aboral ectoderm of the early sea urchin embryo. Gene transfer experiments have defined a 2,300 nucleotide cis-regulatory domain required for the correct spatial and temporal control of this gene. This domain includes at least 20 sites at which relatively stable DNA--protein complexes form in vitro on reaction with embryo nuclear extracts. We report the nucleotide sequence of the whole regulatory domain and map the sites at which high-specificity DNA--protein interactions occur. These were located initially by gel shift assays carried out on progressive restriction digests of given subfragments of the large regulatory domain and were located more exactly by oligonucleotide gel shift competitions. Eight of the sites of specific interaction are unique within the CyIIIa regulatory domain, and the remainder consist of five different sites that occur more than once. We observe some well known sequences also found in regulatory regions of other genes, e.g., "CCAAT" and "octamer" elements. The various sites have been classified regarding putative biological function in other work, and the present studies permit an assessment of the number and complexity of interactions constituting each functional class and of the relative locations of sites of each class. PMID- 2310564 TI - Combined effect of glycerol concentration and cooling velocity on motility and acrosomal integrity of boar spermatozoa frozen in 0.5 ml straws. AB - The interaction of glycerol concentrations of 0-10% and cooling rates from 1 to 1,500 degrees C/min with boar spermatozoa motility and acrosomal integrity (proportion of spermatozoa with normal apical ridge) was studied after thawing 0.5 ml straws at a constant rate. While increasing the glycerol concentration from 0 to 4% progressively improved motility, the percentage of spermatozoa with a normal apical ridge gradually decreased. The magnitudes of the respective changes depended on cooling rate. A peak value of 48.1% and rating 3.8 were obtained in semen protected with 4% glycerol, frozen at 30 degrees C/min. Increasing the glycerol levels above 6% resulted in a gradual decrease in motility. The proportion of spermatozoa with normal apical ridge was highest in semen protected with 0-1% glycerol after cooling at 30 degrees C/min (64.4% and 66.1%, respectively), but at these glycerol concentrations the percentage of motile spermatozoa was low. At the 30 degrees C/min cooling rate, the decline in the proportion of cells with normal apical ridge due to increasing the glycerol levels to 3 and 4% was relatively slow (57.3% and 49.4%, respectively). Cooling at 1 degrees C/min was detrimental to acrosomal integrity, which decreased with increasing glycerol concentration, in contrast to increasing motility, which even at its maximum, remained low. The direct plunging of straws into liquid nitrogen (1,500 degrees C/min) resulted in damaged acrosomes in all spermatozoa with the total loss of motility. Balancing motility and acrosomal integrity, freezing boar semen protected with 3% glycerol by cooling at 30 degrees C/min resulted in optimal survival for boar semen frozen in 0.5 ml French straws. PMID- 2310565 TI - Ultrastructural study on the spermiogenesis and spermatozoon of the metacercariae of Microphallus primas (Digenea), a parasite of Carcinus maenas. AB - The thread-like spermatozoon of the crab parasite Microphallus primas was studied by electron microscopy. A survey of the head region of the spermatozoon reveals three features hitherto unknown in Platyhelminthes spermatozoa. The first is the aberrant inclusion of the nucleus within one of the two axonemes, limited to the head end region. The second is the coexistence, in the same axoneme, of two patterns, 9 + 0 (doublets without dynein arms) and 9 + "1". The third is the presence of a layer of cortical microtubules running longitudinally from the zone where the nucleus goes from axoneme to the tail region (where the two flagella start). The sequence of events in spermatogenesis is similar to that described for most of the Digenea trematodes, and the spermiogenesis process conforms to a common plan in nearly the whole group. PMID- 2310566 TI - Culture media for mouse oocyte maturation affect subsequent embryonic development. AB - These experiments were done to determine whether the culture medium used for the spontaneous maturation of mouse oocytes can affect the subsequent capacity of the ova to become fertilized and complete preimplantation development in vitro and development to live young. Oocytes obtained from antral follicles of gonadotropin primed immature mice underwent spontaneous maturation in control medium, i.e. Eagle's Minimum Essential Medium (MEM) supplemented with 5% fetal bovine serum, or in one of eight different media which were also supplemented with serum. All of the ova were fertilized in Whitten's medium and were assessed for cleavage to the 2-cell stage and for further preimplantation development to blastocysts during culture in Whitten's medium. Three of the eight media used for oocyte maturation improved the capacity of the ova to develop to the blastocyst stage when compared with the control: Waymouth MB 752/1, MEM with non-essential amino acids, and MEM Alpha; Waymouth medium promoted the highest frequency of development of ova to the blastocyst stage. Moreover, the blastocysts derived from oocytes that matured in Waymouth medium contained more cells than blastocysts derived from oocytes that matured in control medium. Although BGJb medium promoted the cleavage of eggs to the 2-cell stage when present during oocyte maturation, it had a detrimental effect on their subsequent preimplantation developmental capacity. Following transfer to foster mothers, more 2-cell stage embryos developed to live young after oocyte maturation in Waymouth medium (21%) than in control medium (13%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310567 TI - An intercellular adhesion protein of rat testis: isolation and preliminary characterization. AB - By using biochemical and immunochemical approaches, we have isolated a rat spermatocyte surface protein of an apparent molecular weight of 80 kd involved in spermatocyte-Sertoli cell recognition in culture. Preliminary characterization of such a molecule has demonstrated that 1) it is a nonintegral membrane component; 2) it possesses a small amount of N-linked oligosaccharides of the high mannose type; and c) it is a stage-specific molecule, being present only in middle-late pachytene spermatocytes. PMID- 2310568 TI - Fertilization envelope assembly in sea urchin eggs inseminated in chloride deficient sea water: II. Biochemical effects. AB - Eggs of the sea urchin Strongylocentrotus purpuratus were fertilized in normal and in several chloride-deficient sea waters ([ Cl-]: normal greater than isethionate greater than methyl sulfonate greater than bromide). The fertilization envelopes (FE) were thinner and failed to harden, and the characteristic I-T transition did not occur. The permeability of the experimental FEs, as determined by release of protein from the perivitelline space, increased in the order of decreasing [Cl-]. Release of the enzymes beta-1,3-glucanase and cortical granule protease were not significantly altered. On the other hand, release of ovoperoxidase was increased three to four times in bromide sea water. Furthermore, a dose-response was observed in varying concentrations of bromide normal sea water. With decreasing chloride (increasing bromide) concentration, more ovoperoxidase activity was observed. Cytochemical localization of ovoperoxidase activity with diaminobenzidine revealed almost a total lack of staining of FEs from bromide-substituted sea water. The results suggest that in chloride-deficient sea waters protein incorporation into the nascent FE is impaired. At least in the case of bromide, the incorporation of ovoperoxidase into the nascent FE was also inhibited. PMID- 2310569 TI - Bovine oviductal fluid components and their potential role in sperm cholesterol efflux. AB - Bovine oviductal fluid (OF) was collected and analyzed throughout the estrous cycle, and the capacity of the protein and lipoprotein components to support cholesterol efflux from bovine sperm was evaluated. Blood was collected and assayed for progesterone (P4) to monitor the estrous cycle. Protein and lipoprotein separation was achieved by density gradient centrifugation. Two major bands were identified. The first (1.056 less than delta 20 less than 1.140 g/ml) corresponded to bovine and rabbit plasma high-density lipoprotein (HDL) based on distribution in the density gradient and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The second band (1.235 less than delta 20 less than 1.243 g/ml) consisted predominantly of oviductal fluid albumin (OFA). Oviductal fluid protein concentration increased as serum P4 decreased around the time of estrus. Mean OF protein concentration was 21.3 mg/ml when serum P4 was lower than 0.5 ng/ml and 6.9 mg/ml when serum P4 was greater than 0.5 ng/ml. An inverse log relationship was found between HDL protein concentration and serum P4. Unesterified cholesterol (UC), cholesteryl ester, and phospholipid (PL) content of HDL for HDL protein concentrations of 3-56.1 micrograms/ml were 1.35-46.2 micrograms/ml, 1.91-44.48 micrograms/ml, and 1.69-59.8 micrograms/ml, respectively. Phosphatidylcholine and -ethanolamine were the major PLs present in the HDL fraction and their molar ratio (4:1 mol/mol) was relatively constant through the estrous cycle. The OFA fraction of the same samples accounted for more than 90% of total protein and for most of the variation in OF protein. To determine the ability of OF components to serve as sperm cholesterol acceptors, OF samples were incubated 1:1 (v/v) with and without 4 X 10(8) bovine sperm in 1.0 ml of modified Tyrode's solution and OF for 2 hr at 39 degrees C. After incubation, HDL and OFA fractions were isolated and analyzed for changes in protein and lipid content. After OF, samples were incubated with sperm, an increase in UC was found in the HDL fractions. UC in HDL increased by 12.1 +/- 1.0 micrograms/ml (means +/- SE) when serum P4 was less than or equal to 0.5 ng/ml. For samples corresponding to higher serum P4, the increase in UC was 3.60 +/- 0.89 micrograms/ml. Values for UC in HDL were corrected for the contribution of UC from OFA of OF samples. Cholesterol efflux from sperm has been implicated in the process of sperm capacitation. These results indicate that HDL from OF is elevated during the follicular phase of the estrous cycle and can serve as an acceptor for bovine sperm cholesterol. PMID- 2310570 TI - Immunological characterization of K+ channel components from the Shaker locus and differential distribution of splicing variants in Drosophila. AB - Antibodies were raised to three portions of the predicted sequences of Shaker, a gene that encodes a family of K+ channel components that are produced by the alternative splicing of transcripts. On immunoblots, the protein products appear to be 65,000-85,000 daltons in size. No smaller products were detected. Immunocytochemistry has revealed a nonuniform distribution of Shaker products in the brain of the adult fly. By comparing antisera directed against regions shared by all the splicing variants to antisera that are directed against one particular group of splicing variants, we have determined that there is a differential distribution of that group of variants. Thus, the alternative splicing of Shaker transcripts appears to produce different subtypes of A-channels in different tissues. PMID- 2310571 TI - The Drosophila Shaker gene codes for a distinctive K+ current in a subset of neurons. AB - A transient K+ current coded by the Shaker gene was identified in muscle and expressed in Xenopus oocytes by injecting cRNA transcribed from a cloned cDNA. The Shaker current has not previously been identified in neurons. Mutational analysis now reveals that in neurons, Shaker is required for expression of a very rapidly inactivating K+ current with a depolarized steady-state inactivation curve. Together, these properties distinguish the Shaker-coded current from similar fast transient K+ currents coded by other genes. The Sh5 mutation further enhanced the depolarization of the Shaker current steady-state inactivation curve. Deletion of the Shaker gene completely removes the transient K+ current from a small percentage of neurons (15%) in a mixed population, and removes a portion of the whole-cell current in about 35% of neurons. The remaining 50% of neurons were apparently unaffected by deletion of the Shaker gene. The unique combination of rapid inactivation and depolarized steady-state inactivation of the Shaker current may reflect a unique functional role for this current in the nervous system such as the rapid repolarization of action potentials. PMID- 2310572 TI - Subconductance behavior in a maxi Ca2(+)-activated K+ channel induced by dendrotoxin-I. AB - Toxin I (DTX-I), a 60-residue peptide belonging to the dendrotoxin family of Mamba snake neurotoxins, is a potent inhibitor of various types of voltage-gated K+ currents. To investigate the sensitivity of another major class of K+ channels to DTX-I, the effect of this toxin was studied on single Ca2(+)-activated K+ channels from rat skeletal muscle incorporated into planar bilayers. Internal (intracellular) DTX-I was found to induce reversibly a long-lived (tau = 40 s), inwardly rectifying subconductance state with 66% of the normal open-state current at +20 mV. Analysis of the kinetics of substate formation and the current voltage behavior of the substate suggest that binding of DTX-I modifies conduction of K+ ions through the pore without affecting the Ca2+ dependence or voltage dependence of gating. These results identify a unique internal binding site for DTX-I (Kd = 90 nM in 50 mM KCl) on a ubiquitous class of high conductance, Ca2(+)-activated K+ channels. PMID- 2310573 TI - Axonal guidance in the chick visual system: posterior tectal membranes induce collapse of growth cones from the temporal retina. AB - Membranes from posterior and anterior thirds of the chick optic tectum were added to explants from nasal and temporal retina. Posterior membranes, and to a lesser extent anterior membranes, cause temporal growth cones to collapse and their axonal processes to retract. Neither tectal source has an effect on nasal growth cones. We interpret these results to mean that there is a tectal activity, stronger in the posterior than the anterior region of the tectum, which helps guide growth cones during the development of the retinotectal map. We believe that in vivo this activity helps to steer temporal growth cones away from the posterior tectum. Nasal growth cones, which must map to the posterior tectum, are resistant to it. In vitro, when posterior membranes contact temporal growth cones over their surface, filopodia and lamellipodia withdraw rapidly. This leads to loss of contact between the growth cone and the substrate, followed by collapse. PMID- 2310574 TI - Gating mechanism of a cloned potassium channel expressed in frog oocytes and mammalian cells. AB - We have cloned a cDNA coding for a delayed rectifier K+ channel from rat brain (RCK1) and rat muscle (RMK1) and expressed it in Xenopus oocytes and in a myoblast cell line (Sol-8). Stably transfected Sol-8 cells exhibited large outward K+ currents, which were indistinguishable from the K+ currents induced in Xenopus oocytes by injection of mRNA transcribed in vitro. RCK1 encodes a K+ channel with a unitary conductance of approximately 14 pS. The steep voltage dependence of channel opening resides in transitions between closed states, whereas the direct transitions into and out of the open state are very rapid and not markedly voltage-dependent. Channel inactivation is very slow, voltage independent, and occurs from the open state only. We present a simple model that incorporates our findings and is consistent with the presumed structural symmetry of a functional K+ channel. PMID- 2310575 TI - The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. AB - Three known genes guide circumferential migrations of pioneer axons and mesodermal cells on the nematode body wall. unc-5 affects dorsal migrations, unc 40 primarily affects ventral migrations, and unc-6 affects migrations in both directions. Circumferential movements still occur, but are misdirected whereas longitudinal movements are normal in these mutants. Pioneer growth cones migrating directly on the epidermis are affected; growth cones migrating along established axon fascicles are normal. Thus these genes affect cell guidance and not cell motility per se. We propose that two opposite, adhesive gradients guide circumferential migrations on the epidermis. unc-5, unc-6, and unc-40 may encode these adhesion molecules or their cellular receptors. Neurons have access to the basal lamina and the basolateral surfaces of the epidermis, but mesodermal cells contact only the basal lamina. These genes probably identify molecular cues on the basal lamina that guide mesodermal migrations. The same basal lamina cues, or perhaps related molecules on the epidermal cell surfaces, guide pioneer neurons. PMID- 2310576 TI - A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation. AB - The alpha-adrenergic agonist oxymetazoline was compared to cocaine and to lidocaine with epinephrine with respect to prevention of epistaxis on nasotracheal intubation. The nares of three groups of 14 patients each were topically pretreated with 4% lidocaine with 1:100,000 epinephrine (group 1), 10% cocaine (group 2), or 0.05% oxymetazoline (group 3) prior to nasotracheal intubation. After intubation, epistaxis was estimated on a scale of 0 to 3, with 0 indicating no bleeding, 1 representing blood on the nasotracheal tube only, 2 indicating blood pooling in the pharynx, and 3 representing blood in the pharynx sufficient to impede intubation. Only 29% of the patients in group 1 displayed no bleeding, whereas 57% of those in group 2 and 86% of those in group 3 had no bleeding. Nonparametric analysis showed a statistically significant difference (p less than 0.013) between oxymetazoline and lidocaine with epinephrine. In addition, heart rate (HR) and blood pressure (BP) were examined prior to administration of the medications; at 5 minutes, 10 minutes, and 15 minutes after administration of the medications; and after intubation. No significant differences were noted (p greater than 0.05) between the medications except for a slightly higher systolic BP for cocaine than for lidocaine with epinephrine at 15 minutes. The results of this double-blind, randomized trial demonstrate that the alpha-adrenergic agonist oxymetazoline is as effective as cocaine, and more effective than lidocaine with epinephrine, for the prevention of epistaxis associated with nasotracheal intubation. PMID- 2310577 TI - Caudal analgesia for pediatric day case surgery: assessment of motor function prior to discharge. AB - The benefits of caudal analgesia are well recognized in the prevention of postoperative pain following pediatric surgery. The possibility of motor weakness may deter anesthetists from using this technique. This study investigates motor function prior to discharge in boys who, as day case patients, received caudal analgesia for pain relief following circumcision. Motor function was assessed using a simple and clinically relevant scale. Three different dosage regimens of bupivacaine were compared. No important motor weakness was demonstrated, and there was no difference with respect to motor block in the three groups. Caudal analgesia may be recommended as a suitable technique for day case patients. PMID- 2310578 TI - Unexpected bronchospasm during spinal anesthesia. AB - Asthma and bronchospastic disease are common in patients presenting for anesthesia. Intraoperative bronchospasm can be a life-threatening problem. One approach to these patients is to use regional anesthesia because it is believed that this will reduce the complication rate. Presented here is a case of bronchospasm occurring during regional anesthesia that was unresponsive to beta agonists. The use of atropine in the treatment of bronchospasm also is discussed. PMID- 2310579 TI - Electroconvulsive therapy--induced hemodynamic changes unmask unsuspected coronary artery disease. AB - Electroconvulsive therapy (ECT) is known to produce increases in heart rate and blood pressure during seizure activity due to sympathetic stimulation and systemic catecholamine surges. These intense, brief hemodynamic changes can adversely affect myocardial oxygen supply and demand. In patients with compromised myocardial circulation, ECT can unmask undiagnosed cardiac disease. In this case report, ECT was performed on a 64-year-old white male with negative cardiac history. The patient awakened complaining of chest pain and ST wave depression was noted on the electrocardiogram. Cardiology consultation and cardiac catheterization were followed by coronary artery bypass surgery for significant coronary artery stenosis prior to resumption of ECT treatments. The physiological changes that occur during ECT are discussed, as well as pitfalls in evaluation of these patients for ECT treatment. PMID- 2310580 TI - Unilateral pulmonary edema following acute subglottic edema. AB - Presented here is a case of unilateral pulmonary edema following acute subglottic edema after removal of an endotracheal tube. A 3-year-old boy, diagnosed as having nondiphtheric croup and pectus excavatum deformity, was scheduled for repair of a cleft lip. No complication occurred during the operation. After removal of the endotracheal tube, he showed dyspnea and cyanosis and was later found to have acute subglottic edema. After reintubation of the trachea, frothy pink fluid was discharged from the tube, and chest roentgenogram showed a right sided alveolar infiltrate. Many factors may cause unilateral pulmonary edema, but it is suggested that acute subglottic edema and unilateral bronchial fragility strongly affected this episode. PMID- 2310581 TI - Application of the Grieshaber air system to maintain endotracheal tube cuff pressure. AB - The Grieshaber Air System was designed to maintain intraocular pressure during ophthalmologic surgery. It also has been used to maintain pressure in leaking endotracheal tube cuffs. It is a very useful device, especially if the intubation is difficult or the patient's position precludes replacement of the endotracheal tube. Two patients are presented in whom the system was used to maintain endotracheal tube cuff pressure. PMID- 2310582 TI - Pulse oximetry in MRI units. PMID- 2310583 TI - Pulmonary macrophages can stimulate cell growth of bovine bronchial epithelial cells. AB - Macrophages are thought to participate in tissue repair following injury by releasing growth factors into the local environment. To evaluate whether pulmonary macrophages can mediate airway epithelial repair, we attempted to determine if pulmonary macrophages can stimulate growth of bovine bronchial epithelial cells in vitro. Bronchial epithelial cells isolated by protease digestion of the bovine bronchi were plated into tissue culture dishes with and without macrophage-conditioned medium. Bronchial epithelial cells cultured with macrophage-conditioned medium showed a significantly greater cell growth than those without macrophage-conditioned medium when assessed by direct enumeration of the cell numbers and by clonal growth assay. Stimulation of proliferation was confirmed by autoradiography using [3H]thymidine uptake into cell nuclei. Co culture of pulmonary macrophages with bronchial epithelial cells also led to an increase in cell number. Immunohistochemical staining of the proliferating cells showed that these cells were positively stained by anti-keratin antibodies confirming that they were bronchial epithelial cells. Partial characterization of the activity in macrophage-conditioned medium showed that it was nondialyzable, pepsin- and acid-labile, and lipid-inextractable. Sephadex G-75 column fractionation indicated this activity existed in a high molecular fraction, thus suggesting a peptide. DEAE ion exchange chromatography revealed 3 peaks of stimulating activity. One peak resulted in a decrease in cell number, suggesting a possible inhibitory activity. The DEAE results thus suggest that macrophages may release several factors that can affect bronchial epithelial cell proliferation. In conclusion, pulmonary macrophages stimulate cell proliferation of bronchial epithelial cells in vitro. The stimulatory activity that may be heterogeneous appears to have the properties of a peptide. PMID- 2310584 TI - Inhibition of human leukocyte elastase bound to elastin: relative ineffectiveness and two mechanisms of inhibitory activity. AB - Human leukocyte elastase (HLE) has been demonstrated on lung elastic fibers in areas of pulmonary emphysema. In vitro studies in our laboratory have shown that HLE-elastin complexes may be remarkably stable. We tested the possibility that elastin-bound HLE may retain catalytic activity in the presence of inhibitors that are effective against free HLE and found: (1) alpha-1-proteinase inhibitor (alpha 1PI), antileukoprotease (ALP), and eglin C inhibited free HLE on an approximately 1:1 molar basis, measured with either 3H-elastin or a synthetic peptide substrate; (2) the ability of each inhibitor to control catalytic activity of HLE when complexed with elastin was impaired (e.g., in a 24-h assay, a 70-fold molar excess of alpha 1PI gave only 93% inhibition of HLE); and (3) a chloromethyl ketone inhibitor of HLE gave qualitatively similar results, although at the low enzyme concentrations used it was a less effective inhibitor of free and elastin-bound enzyme than were the polypeptide inhibitors. Further, we found evidence for two distinct mechanisms of inhibition of elastin-bound HLE. alpha 1PI and eglin C prevented elastin solubilization largely by enhancing net dissociation of HLE from the complexes; enzyme remaining bound to the substrate retained essentially full activity. In contrast, ALP and the chloromethyl ketone prevented elastin solubilization by binding to the complexes and inhibiting the enzyme in situ. These results may have implications regarding progressive elastin solubilization in vivo and should stimulate further investigation of enzyme activity in heterogeneous systems in which one or more reactants are insoluble. PMID- 2310585 TI - The use of quantitative two-dimensional gel electrophoresis to analyze changes in alveolar macrophage proteins in humans exposed to ozone. AB - Acute exposure of humans to 0.4 ppm ozone is known to cause production of components that mediate inflammation and damage in the lung. However, ozone may cause even more extensive changes in the lung than those currently measured by traditional enzymatic or immunologic methods. The contribution of alveolar macrophages to these processes is not well understood. Therefore we have used molecular techniques to measure changes in the total spectrum of alveolar macrophage proteins in humans exposed to ozone. In this study, 8 human volunteers were each exposed to 0.4 ppm ozone and to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage was performed and alveolar macrophages were isolated. Changes in proteins made by these cells after air or ozone exposure were analyzed by high-resolution two-dimensional gel electrophoresis, using computerized densitometry to quantify changes in individual proteins. Of the nearly 900 proteins analyzed, 45 (5.1%) were synthesized at a significantly increased rate following ozone exposure, while 78 (8.8%) were synthesized at a significantly reduced rate. These results indicate that exposure of humans to ozone causes extensive changes in the spectrum of macrophage proteins being produced. Quantitative two-dimensional gel electrophoresis is a highly sensitive technique that may reveal much more information about the in vivo effects of a pollutant than has previously been available. Furthermore, the ability to survey large numbers of macrophage proteins after exposure to various inhaled pollutants may allow a better understanding of the mechanisms of action of these agents, as well as provide new biomarkers of pollutant exposure. PMID- 2310586 TI - Guidelines for physician training in fetal echocardiography: recommendations of the Society of Pediatric Echocardiography Committee on Physician Training. PMID- 2310587 TI - Prenatal detection of restrictive foramen ovale. AB - The foramen ovale is an important communication between the two sides of the heart prenatally, allowing the left ventricle to carry its share of the prenatal circulation and providing flow for growth of left ventricular structures. Restriction of the foramen ovale appears to be a serious disorder of the fetus and can be associated with fetal hydrops, arrhythmias, and other signs of major fetal compromise. This article reviews our experience with restriction of the foramen ovale and provides a summary of the pathologic and echocardiographic literature related to the etiology and effects of restrictive foramen ovale in the fetus. PMID- 2310588 TI - Ventricular volume overload in the human fetus: observations from fetal echocardiography. AB - We examined two groups of fetuses in which echocardiography had been performed and in which ventricular volume overload eventually led to fetal hydrops. The first group (18 fetuses) had atrioventricular valve regurgitation and almost all of the fetuses had structural heart disease. No fetus in this group survived the neonatal period; only two of the pregnancies in this first group were terminated. A second group of three fetuses had ventricular volume overload from sacrococcygeal teratomas at 21 to 24 weeks' gestation. These fetuses also had nonimmune hydrops (or it developed), but they did not have structural heart disease or atrioventricular valve regurgitation. Combined ventricular output in this group was calculated by Doppler ultrasound to be greater than twice the normal output for fetuses of the expected gestational weight. The proportion of the combined output to the lower body and the placenta was increased with the increase to the teratoma, exceeding the increase to the placenta. In one fetus, serial study demonstrated increasing output and the development of hydrops. Intrauterine surgery was undertaken to control the high output failure. The abnormal variables tended to revert to normal after replacement of blood loss, and the hydrops disappeared. The pregnancy continued until the spontaneous rupture of membranes at 26 weeks' gestation forced delivery by cesarean section. The infant died from severe hyaline membrane disease. These findings suggest that, in some circumstances, fetal hydrops is a late sign of cardiac failure and heralds incipient death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310589 TI - Premature constriction of the ductus arteriosus. AB - Prostaglandin synthetase inhibition in the fetus may induce constriction of the ductus arteriosus. Clinical experience is now accumulating that proves that this potential complication is reversible and that it is easily diagnosed by Doppler echocardiography. PMID- 2310590 TI - Flow velocity acceleration in the left ventricle: a useful Doppler echocardiographic sign of hemodynamically significant mitral regurgitation. AB - Doppler echocardiography is a sensitive method to detect mitral regurgitation in patients with both native and prosthetic valves. However, estimates of the amount of mitral regurgitation remain semiquantitative, and even severe mitral regurgitation may be underestimated in the presence of markedly eccentric regurgitant jets or acoustic shadowing of the left atrium by mitral or aortic prostheses. This report describes the Doppler findings in 10 patients with severe native valve mitral regurgitation (angiographic grade III or IV) and in 15 patients with severe bioprosthetic mitral regurgitation that required valve replacement. An increase in peak mitral flow velocity above normal values was seen in eight of 10 patients with severe native valve mitral regurgitation (greater than or equal to 130 cm per second) and 11 of 15 patients with severe prosthetic valve mitral regurgitation (greater than or equal to 210 cm per second). One of 10 patients with a native valve and four of 15 patients with a bioprosthetic valve appeared to have only a localized left atrial systolic flow disturbance, incorrectly suggesting that the mitral regurgitation was mild. However, in all patients with severe mitral regurgitation, a low velocity (less than 100 cm per second) flow signal could be recorded in the left ventricle that was directed toward the mitral valve in systole. This flow signal showed a gradual increase in velocity as the sample volume was moved toward the mitral valve, with an abrupt further increase on entry into the left atrium. This signal was continuous with antegrade mitral flow and had the same orientation as mitral regurgitation recorded by continuous wave technique from the apex. A similar flow signal was not recorded in the left ventricle of any individual in a control group of 30 patients who had no mitral regurgitation or who had angiographic grade I or II mitral regurgitation. These findings suggest that acceleration of left ventricle flow toward the mitral valve in systole is only recorded when there is hemodynamically significant mitral regurgitation that is approximately equal to angiographic grade III or IV. Recognition of this Doppler finding may help in the estimation of mitral regurgitation severity, especially in difficult diagnostic situations. PMID- 2310591 TI - Fetal echocardiography: a large clinical experience and follow-up. AB - We reviewed our experience with 382 fetal echocardiograms. Complete studies were not possible for three pregnancies because of either fetal position or maternal obesity. Studies were performed for fetal arrhythmia (28%), maternal factors (21%), fetal anomaly (11%) and family history of congenital heart disease (40%). There was a recurrence of heart disease in two of 153 patients (1.3%). Arrhythmia was the most common finding (82 of 382 patients). Premature atrial and ventricular contractions were the most common arrhythmia, and structural defects were present in four of 58 patients (6.8%) with premature contractions. Fetal heart defects (n = 44) were identified in 40 of 382 (10%) referrals. The defects were complete atrioventricular block (13), ventricular septal defect (4), atrioventricular canal (5), cardiac mass (3), ectopia cordis (2), thoracopagus (2), hypoplastic left ventricle (2), hypoplastic right ventricle (2), atrial flutter (2), pulmonic stenosis (1), single ventricle (2), Uhl's anomaly (1), Ebstein's anomaly (1), mitral atresia (1), d-transposition of the great vessels (1), tetralogy of Fallot with absent pulmonary valve (1), and atrial septal defect and ventricular septal defect (1). There were three false positive (99% specificity) and two false negative (95% sensitivity) fetal echocardiograms. The survival rates for referred patients with heart defects was: live born and perinatal survivor, 54%; perinatal death, 31%; still birth, 11%; and termination of pregnancy, 4%. Fetal echocardiography is accurate, and the abnormalities detected appear to be more severe than those detected on newborn screening. PMID- 2310592 TI - Pressure half-time in aortic regurgitation: evaluation with Doppler in a cardiovascular hydromechanical simulator and in a computer model. AB - Doppler echocardiographic determination of pressure half-time has been proposed as a method of assessing the severity of aortic regurgitation. To evaluate this method, we assessed the relation between pressure half-time and simulated aortic regurgitant flow under various conditions in two models of the cardiovascular system. In a hydromechanical model we assessed the influence of total peripheral resistance and arterial compliance on the pressure half-time as measured by continuous wave Doppler echocardiography. In a computer model that used the half time of the pressure gradient between the aorta and the left ventricle as an expression of pressure half-time, we assessed the influence of total peripheral resistance and arterial compliance and also the influence of left ventricular compliance on pressure half-time. In both models, although we found an inverse relation between regurgitant orifice area and pressure half-time, changing total peripheral resistance and arterial compliance (but not left ventricular compliance) within the physiologic range significantly altered the pressure half times. We concluded that the influence of total peripheral resistance and arterial compliance limits the usefulness of Doppler echocardiographic determination of pressure half-time as a method of assessing the severity of aortic regurgitation. PMID- 2310593 TI - Age-related prevalence of valvular regurgitation in normal subjects: a comprehensive color flow examination of 118 volunteers. AB - We prospectively assessed the influence of aging on the prevalence of valvular regurgitation by using color flow imaging. One hundred eighteen healthy volunteers (21 to 82 years old) had a two-dimensional Doppler echocardiographic study that included color flow imaging to assess valvular regurgitation and that was semiquantitated by mapping the dimensions of the color flow regurgitant jet in orthogonal views. The subjects were divided into two groups: group 1 consisted of subjects who were younger than 50 years old (n = 61), and group 2 consisted of subjects who were at least 50 years old (n = 57). Mitral regurgitation was detected in 57 (48%) of the 118 subjects: 24 subjects (39%) in group 1 and 33 subjects (58%) in group 2. The severity of mitral regurgitation was trivial to mild. Aortic regurgitation was detected in 13 (11%) of the 118 subjects, all in group 2. The severity was trivial to mild. Tricuspid regurgitation was detected in 77 (65%) of the 118 subjects: 35 (57%) in group 1 and 42 (74%) in group 2. The severity was trivial to mild. Pulmonary regurgitation was detected in 24 (31%) of 78 subjects: nine (22%) in group 1 and 15 (41%) in group 2. The severity was trivial. These findings suggest that valvular regurgitation of a trivial or mild degree is a frequent finding in normal subjects and that it increases with age. PMID- 2310594 TI - Echocardiographic and hemodynamic characteristics of atrial septal defects created by percutaneous valvuloplasty. AB - Twenty-nine patients were studied by pulsed, continuous wave, and color Doppler before and after percutaneous transseptal valvuloplasty. New atrial septal defects were detected in 14 patients, and the patients were monitored for up to 320 days after the procedure. The diameter of the defect, best evaluated by the transesophageal approach, was 3 to 15 mm. A narrow, high velocity (1.4 to 3.1 meters per second) left-to-right shunt jet was detected in 13 of 14 patients. The shunt jet was continuous in nine of 14 patients, late systolic-holodiastolic in four patients, and bidirectional in one patient. Cardiac catheterization in nine patients confirmed the Doppler findings and demonstrated a peak pressure gradient of 10 to 32 mm Hg between the left and right atria. Oximetry revealed a calculated pulmonary to systemic flow ratio ranging from 2.3:1 in the patient with the largest atrial septal defect by echocardiography to 1:1 (no oxygen saturation step-up) in the patient with the smallest atrial septal defect. In the three patients who underwent cardiac surgery, the operative findings confirmed those of echocardiography. We concluded that atrial septal defects are common after transseptal valvuloplasty. Usually, their relatively small size and the underlying valvular disease that produces high left atrial pressure are responsible for the high pressure gradient between the left and right atria. This results in the high velocity and continuous shunt jet detected by Doppler echocardiography. PMID- 2310595 TI - Abbreviated aortic insufficiency in aortic dissection caused by prolapse of the intimal flap. AB - Aortic insufficiency was identified in a patient with acute ascending aortic dissection. The aortic insufficiency was limited to the first half of diastole by prolapse of the intimal flap against the regurgitant orifice. This unusual pathophysiology was well demonstrated by two-dimensional and color flow Doppler echocardiography. PMID- 2310596 TI - Incomplete left atrial appendage ligation that simulates mitral regurgitation. PMID- 2310597 TI - Mitral annular motion: physiologic significance. PMID- 2310598 TI - Cyanotic disease in the fetus. PMID- 2310599 TI - The prognostic significance of growth pattern and its relation to tumor cell nuclear DNA content in endometrial carcinoma. AB - Hysterectomy specimens from 21 endometrial carcinoma patients, who died from their disease, and 23 patients selected at random from 307 survivors, were analysed for tumor growth pattern and tumor cell nuclear DNA content. The results indicate that tumor growth pattern, reflected by the mode of infiltration, is significantly correlated to the clinical course of the disease. Patients with carcinomas exhibiting contiguous growth pattern had a better outcome than patients with discontiguously growing carcinomas. It was also found that tumor growth pattern correlated well with tumor nuclear DNA content. It is suggested that the pattern of infiltration of the tumors is a sensitive predictor of prognosis and that this prognostic information, which only can be obtained postoperatively, to a large extent is reflected by tumor cell nuclear DNA content in curetted diagnostic material, obtained prior to treatment. PMID- 2310600 TI - A phase II study of 5-fluorouracil/cisplatinum in recurrent cervical cancer. AB - Thirty-seven patients with recurrent cervical carcinoma entered a phase II study of cisplatinum and 5-fluorouracil (5-FU). They were divided into patients with recurrent lesions outside previously irradiated area (group 1) and those with at least one recurrent lesion inside this volume (group 2). The treatment schedule consisted of 5-FU 1,000 mg/m2 i.v. days 1 to 5 and cisplatinum 100 mg/m2 i.v. day 1. Thirty-two patients were evaluable for response and toxicity. In group 1, 4 out of 19 patients had complete response with a median duration of 18 months, 9 out of 19 had partial response with a median duration of 10 months. Only 2 out of 13 patients in group 2 achieved partial response. All patients suffered from nausea and vomiting. The dose limiting factor was bone marrow suppression. The response rate in group 1 (68%) is impressive and higher than previously reported after other chemotherapy regimens. We found, however, the regimen too toxic for patients with central recurrences in previously irradiated areas, though some of these patients achieved substantial pain relief. PMID- 2310601 TI - Prognosis of endometrial carcinoma stage I in two Swedish regions. A study with special regard to the effects of intracavitary irradiation with high dose-rate afterloading technique or with low dose-rate radium. AB - A high dose-rate afterloading technique (60Co) was compared with a low dose-rate packing method (226Ra) in the treatment of endometrial carcinoma stage I. In all, 1,021 patients treated during the period 1977-1986 at two Swedish gynecologic oncology centers were analyzed regarding treatment set-up, histopathologic outcome in the operative specimens, recurrence rates, survival rates and radiation side effects. Complete tumor eradication in the operative specimen was achieved in 80% after radium therapy and in 60% after irradiation by the high dose-rate technique. The overall recurrence rate was 15.7% in the radium packing series and 11.5% after cobalt afterloading treatment. The risk of pelvic recurrences increased by 2.1-2.6 if hysterectomy was replaced by dilatation and curettage. The two radiation techniques seemed to be comparable with regard to the risk of both pelvic recurrences and distant metastases. The 5-year crude survival rates were 85% in the afterloading series and 82% in the radium series. The corrected survival rates were similar (90%) for the two techniques. Age, tumor grade and uterine size were significant prognostic factors with regard to the probability of death due to cancer. Early radiation reactions had quite similar rates in the two series, whereas late radiation reactions were more frequent in the high dose-rate afterloading group in the 10-12 Gy dose fraction range, but not in the 5-8 Gy range. The radium packing method seemed to give a higher frequency of tumor-free operative specimens in this study, but with regard to recurrence rates and survival probabilities the techniques were comparable. Since the different proportion of surgery in the two series and the histopathologic evaluation might have influenced the rate of local tumor eradication in the operative specimens and the risk of pelvic recurrences the results must be assessed with great caution and only a crude comparison of the two treatment techniques could be made. PMID- 2310602 TI - Results of cystectomy with and without preoperative radiotherapy in carcinoma of the urinary bladder. AB - During a period of 13 years, 84 patients underwent total cystectomy for transitional cell carcinoma of the bladder. The corrected 5-year survival rate was 58%. The operative mortality was 5 patients (6%). The 5-year survival rate of 42 patients who were treated by surgery alone was 53%, whereas that of 42 patients who received preoperative radiation of 30-40 Gy was 65%. The prognoses of the patients were dependent on the histological differentiation and the extent of the primary tumour within each treatment group. PMID- 2310603 TI - DNA cytometric and histologic findings in mouse tumors (BP and S 180) with different response to treatment with tumor necrosis factor. AB - DNA cytometric and histopathologic investigations were performed in two tumor models (BP and S 180) which differed in their sensitivity to tumor necrosis factor (TNF). TNF induced strong necrosis in both tumors, but only the sarcoma 180 showed total regression. After TNF administration DNA cytometry revealed in the BP tumor an increase of cells in the S-phase, and in the S 180 tumor a loss of aneuploid cell populations. Histologic examination revealed a more obvious effect of TNF on tumor blood vessels in BP tumor, whereas infiltration of inflammatory cells was observed only in the S 180 tumor. We concluded that cell infiltration may be of importance for tumor regression and that aneuploid cell populations are more sensitive to TNF treatment than eudiploid cells. PMID- 2310604 TI - Radiostrontium-induced oncogenesis and the role of immunosuppression. II. Influence of 90Sr dose, adult thymectomy and antilymphocyteglobulin treatment on the development of lympho-reticular and extraskeletal, neoplastic lesions in CBA mice. AB - The significance of depressed immune function for the development and progression of tumours induced by 90Sr (mainly osteosarcomas and malignant lymphomas) was investigated in a series of experiments by comparing the tumour responses in normal mice with those in immunocompromised mice. The present paper (part II) reports on lympho-reticular (LR) and extraskeletal neoplastic lesions in male CBA/SU mice after exposure to different single doses of 90Sr with or without additional immunosuppression by adult thymectomy (ATx) and/or prolonged antilymphocyteglobulin (ALG) treatment. Neoplastic lesions in bone were reported in part I. The status of the animal's immune system and responsive ability were examined in parallel experiments. The tumour yields were analysed in relation to the dosage of 90Sr and the immunosuppressive treatments employed. Although the incidences and latency times of induced tumours were clearly dose-dependent, they were never significantly influenced by ATx/ALG treatments. Thus, no substantial support was gained for the theory that the immune system plays a controlling or modifying role in 90Sr carcinogenesis. The results, which are in agreement with the bone tumour responses, suggest that 90Sr induced tumours either do not express the antigens necessary for immune rejection or that the decline in immune responsiveness induced by ATx/ALG was of little consequence for tumour development and spread. The pathogenesis of 90Sr induced malignant lymphomas (MLs) and their immunophenotypes are discussed. PMID- 2310605 TI - Safeguard the identity of cancer nurses. PMID- 2310606 TI - Training of surgeons in oncology--a personal view. PMID- 2310607 TI - Incidence of sporadic and familial medullary thyroid carcinoma in Sweden 1959 through 1981. A nationwide study in 126 patients. Swedish MCT Study Group. AB - Medullary thyroid carcinoma (MTC) was identified in 276 patients (in 27 diagnosed at autopsy) by a review of virtually all 6,513 notifications of primary thyroid cancer ot the National Cancer Registry in Sweden 1959 through 1981. The diagnosis was confirmed in 268 of the 276 cases by histopathological and histochemical reexamination. Anamnestic data and morphological characteristics indicated that 208 (75%) patients had sporadic and 68 (25%) familial MTC. The mean ages at diagnosis of these two groups were 57.0 and 42.6 years respectively. The age standardized incidence rate per 10(5) inhabitants was 0.18 for males and 0.23 for females. The age-specific incidence of sporadic MTC increased markedly with age, whereas no unequivocal rise was found after the age of 20 for familial disease. Standardized morbidity ratios (SMR), calculated separately for each of the six Swedish health care regions, revealed a roughly two-fold and mostly non significant geographical variation in the occurrence of sporadic MTC. SMR for familial disease varied, however, between 0 and 306 and deviated highly significantly from the national average in four of the six regions. Regional differences in diagnostic intensity were considered unlikely as the sole explanation of this finding. PMID- 2310608 TI - Supplemental taurine in diabetic rats: effects on plasma glucose and triglycerides. AB - The present study has indicated that significant shifts in plasma, urinary, and tissue taurine and in non-taurine dialyzable amines occur in the STZ-induced diabetic rat, especially in the kidney. Taurine administration at relatively low dosage ameliorated only kidney taurine concentration. Anticipated alterations in plasma glucose and creatinine were observed but neither of these changes was affected by taurine administration. Similarly, urinary output of creatinine, glucose, and NAG increased significantly among diabetic rats, but none of these were detectably influenced by taurine. Increases in plasma triglycerides observed in STZ-induced diabetes appear to be attenuated by taurine administration, and although cholesterol concentrations were lower in taurine-treated rats, the differences were not statistically significant. These findings should encourage further studies of these effects in rats as a useful model for several complications of human diabetes including atherosclerosis, retinopathy, and nephropathy. PMID- 2310609 TI - Effect of clofibrate on peroxisomal lignoceroyl-CoA ligase activity. AB - The effect of a 2-week clofibrate (0.5%)-fortified diet on peroxisomal palmitoyl CoA and lignoceroyl-CoA ligases was studied. The activities of palmitoyl-CoA and lignoceroyl-CoA ligases in peroxisomes isolated from clofibrate-treated animals were 4.4- and 4.0-fold higher than those of the controls. The different degrees of increases in these two enzyme activities support the previous conclusions that in peroxisomes palmitoyl-CoA ligase and lignoceroyl-CoA ligase are different enzymes. Since clofibrate treatment increases both of these peroxisomal acyl-CoA ligase activities and normal palmitoyl-CoA ligase is the source of the partial activity for the oxidation of lignoceric acid in X-ALD, treatment with a hypolipidemic drug, which can increase human peroxisomal enzyme activities, may be helpful in lowering the amount of the pathogen, VLC fatty acids, in X-ALD. PMID- 2310610 TI - The effect of a low concentration of ATP on the glucocorticoid receptor: evidence for a novel form of the receptor. PMID- 2310611 TI - Alkaline phosphatase and phosphoamino acid phosphatases in normal and cancerous tissues of the human larynx. AB - The activities of alkaline phosphatase and phosphoamino acid phosphatases were measured in normal and cancerous regions of the human larynx. For each larynx, alkaline phosphatase and phosphotyrosine phosphatase activities were higher in the tumor than in the corresponding normal tissue. Phosphothreonine and phosphoserine phosphatase activities were relatively low and there were no consistent trends. The increased alkaline phosphatase activity in the tumors supports histological observations that ossification of cartilage seems to occur at the site of invasion; the phosphatase acting on phosphotyrosine could serve as a regulator of cell differentiation during tumorigenesis. PMID- 2310612 TI - Allylamine-induced phenotypic modulation of aortic smooth muscle cells. AB - Subchronic exposure of Sprague-Dawley rats for 20 days to allylamine resulted in a modulation of phenotypic expression of smooth muscle cells in vitro as characterized by alterations in cell morphology, ultrastructure, contractile function and synthetic/proliferative capabilities. Smooth muscle cells isolated from control animals were elongated and spindle-shaped at confluence, and contained a dense network of myofilaments. In contrast, cells isolated from treated animals were rounded and contained numerous ribosomes. Only cells obtained from control animals contracted in response to noradrenalin exposure (10 microM) in vitro. Smooth muscle cells obtained from allylamine-treated rats exhibited a 114% increase in 3H-thymidine uptake and a 204% increase in 3H proline incorporation into collagen at confluence in comparison to controls. Serially passaged cells isolated from treated animals showed a similar enhancement (100%) in 3H-thymidine uptake. These results suggest that allylamine modulates aortic smooth muscle cells in vivo from a contractile to a more synthetic phenotype. PMID- 2310613 TI - The microanatomy of the intrahepatic bile duct in polycystic disease: comparison of the cpk mouse and human. AB - The cpk mutation in mice produces a lethal recessive form of polycystic kidney disease (PKD) that, like human forms of the condition, is associated with an age related incidence of hepatic cysts. Injection of plastic into the biliary tree of affected animals revealed that these cysts arise from focal dilatations of the epithelial lining that may enlarge to the point that they obstruct the bile ducts. This concept was supported by histological and scanning and electron microscopic studies. No evidence could be found of primary obstruction of the biliary tree. The same techniques were then employed in specimens of human liver from patients with both recessive (ARPKD) and dominantly inherited PKD (ADPKD). Similar abnormalities of the biliary tree were identified. These abnormalities were not found in control liver samples from patients without PKD. The liver of the patient with ADPKD also demonstrated many von Meyenburg complexes. These were related to some cyst development, but these complexes freely communicated with bile ducts, contrary to currently held opinion. We conclude that hepatic abnormalities in the cpk mouse and human PKD arise from changes in bile ducts that are analogous to the renal lesions. PMID- 2310614 TI - Development of intrahepatic bile ducts in rat foetal liver explants in vitro. AB - The origin of intrahepatic bile ducts was investigated in organ cultures of 13, 16 and 19-day foetal rat livers embedded for up to 10 days in a semi-solid agar gel on a filter-raft assembly. Following 10 days in culture, 13-day foetal explants consisted of liver cell trabeculae lined by endothelial cells. Although maturation of the liver cells and bile canaliculi was observed, duct development was found in less than 10% of the explants. Supplementation of the media with putative inducers of bile duct development or culture of explants adjacent to other tissues did not induce regular duct development. By contrast, explants from the porta hepatis of 19-day foetuses cultured for 4 days, but not 10 days, regularly contained duct-like structures. The formation of the few ducts in cultures of 13-day foetal liver explants indicates that these cells can arise by transformation of hepatoblasts but that specific inducers of development are required for predictable and continuous differentiation of biliary epithelial cells. PMID- 2310615 TI - Epithelial regeneration in collagen-coated and uncoated patch grafts implanted into dog tracheas. AB - The paper compares ultrastructural regeneration of the tracheal epithelium on patch grafts coated or not coated with collagen. A longitudinal patch window 2 x 1 cm (four cartilaginous rings in cephalocaudal extent) was made on the ventral wall of the cervical trachea in dogs, and replaced by a polypropylene Malex mesh graft. Grafts coated with collagen allowed normal connective tissue ingrowth and subsequent epithelial spreading. From the cut edge, flat, stratified, poorly differentiated cells migrated and spread on the newly formed stroma. Six weeks after the operation, the prosthesis was thoroughly covered by pseudostratified ciliated columnar epithelium with a newly formed basal lamina. On uncoated grafts, in contrast, some regenerated ciliated cells formed compound cilia or irregular microvilli and dilated endoplasmic reticulum. At 6 weeks, no normal basal cells differentiated, although some bizarre flat cells with extremely extended cytoplasm were located in the basal area of the epithelium. The basal lamina was thick and discontinuous. The underlying stroma included abnormally elongated fibroblasts with condensed cytoplasm and curved, randomly dispersed collagen fibrils. These ultrastructural results indicate that (1) regenerated epithelial cells were derived from poorly differentiated cells; (2) a plastic implant may lead to abnormal regeneration in the connective tissues and epithelium; and (3) collagen coating of the graft may allow fibroblasts to produce normal connective tissue substances. PMID- 2310616 TI - Biliary lipid secretion during the prereplicative phase of rat liver regeneration. AB - The prereplicative phase-related changes in spontaneous and taurocholate-induced biliary lipid secretion were studied in anaesthetized male Wistar rats (250 g). Rats underwent two-thirds hepatectomy 1, 6 or 12 h before starting to collect bile samples. As compared with non-hepatectomized rats, biliary lipid secretion was increased at 1 h after hepatectomy and then restored to values similar to the control group up to 12 h after hepatectomy. In separate experiments, taurocholate was infused (200 nmol/min/g calculated liver weight) through the jugular vein over 80 min. Both taurocholate-induced bile flow and bile acid output were similar in control and hepatectomized rats, regardless of the time of the prereplicative phase considered. By contrast, taurocholate-induced lecithin and cholesterol outputs were markedly modified. The former was lowered throughout the prereplicative phase, whereas the latter increased at 6 h and decreased at 12 h. In summary, these results indicate that shortly after hepatectomy bile acid induced biliary lipid secretion is profoundly modified, probably due to changes in the plasma membrane involved in preparing the hepatocyte to enter the cell cycle. PMID- 2310617 TI - Effect of dengue virus-induced cytotoxin on capillary permeability. AB - Capillary permeability is increased in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) but its genesis is not known. Dengue type 2 virus (DV) induces production of a cytokine (CF2) by mouse macrophages. The present study was undertaken to investigate the effect of CF2 on capillary permeability. It was observed that intraperitoneal inoculation of CF2 in mice increased the capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radioactive iodine (125I) or Evan's blue dye in the peritoneal cavity. Peak leakage occurred at 30 min and the vascular integrity was restored by 1-2 h. The increase in capillary permeability was abrogated by pretreatment of mice with avil (H1 receptor blocker) but not by ranitidine (H2 receptor blocker). The findings thus show that DV-induced CF2 increases the capillary permeability via release of histamine. PMID- 2310618 TI - Histamine, histamine formation capacity and gastrin in cysteamine-induced peptic ulcer. AB - We attempted to induce chronic peptic ulcer in the rat by injection of consecutive doses of cysteamine. We investigated the incidence of peptic ulceration and measured gastric mucosal histamine, histamine formation capacity (HFC), plasma gastrin and tissue (oesophagus, duodenum, liver and lung) histamine in rats 1, 7, 14, 21, and 28 days after injection of cysteamine-HCl (300 mg/kg s.c. and 100 mg/kg 8 h later). Saline injections were used in control rats. After 24 h all rats given cysteamine had duodenal ulcers and the ulcer incidences after 7 and 14 days were 60 and 40%, respectively. After Day 21 no ulcers were found. Microscopy revealed ulcer healing seen as epithelialized scars from Day 14 onwards. A rising incidence of gastric metaplasia of the duodenal mucosa was noted from Day 7 after cysteamine treatment, which may have pathophysiological significance. Gastric mucosal histamine was higher and plasma gastrin was lower after 24 h compared with controls and values obtained later in the study. Rats with duodenal ulceration had significantly higher gastric mucosal histamine than those without lesions and control rats. A direct relationship was found between plasma gastrin and HFC in rats given cysteamine. A small but significant increase in histamine content of the liver was also observed after 24 h. No significant changes were found in other tissue specimens. Thus, a rise in gastric histamine is associated with duodenal ulcers in this model. PMID- 2310619 TI - [Generational differences in perception of menstruation and attitude to menstruation]. AB - Based upon a model of individual differences in menstrual experiences the study concerns the question of similarities and difference in menstrual experience and attitudes between mothers and their daughters. 60 mothers (mean age 46.5 years) and 60 daughters (mean age 19.9 years) were investigated using a comprehensive questionnaire which included standardized measures such as the German version of the Menstrual Attitude Questionnaire. Comparisons of both groups revealed significant differences in relation to sex education, preparation for menstruation, and the experience of menarche, which were described more positive by the generation of the daughters. Differences in menstrual cycle effects on wellbeing and behavior were less clear. Behavioral changes and restrictions both demonstrated the significance of the mothers influence on their daughters. Inspite of more positive conditions for a "menstruation related socialization" mothers and daughters showed only slight differences in their menstrual attitudes. This result could confirm the importance and persistence of cultural norms. PMID- 2310620 TI - [The hyperventilation syndrome as psychosomatic components of heart transplantation: case study]. AB - The case study presents a patient with severe disturbance of self-esteem, suicidal family-background, narcissistic trauma and psychosomatic illness in form of a hyperventilation syndrome in the light of his heart transplantation. Helplessness and hopelessness of his psychological situation, his fear of separation, his paralyzing inability to come to any decision are seen against the background of a situation of absolute stress in which he had to struggle against his anxieties and fears and presumptions about the donor organ. There also is discussed whether a patient with such severe disturbances should really be accepted as a donor organ recipient, as well as whether in this case a supportive or analytic therapy would have been the appropriate choice. Annotations of the author about personal difficulties in therapy and at last its failing are added. PMID- 2310621 TI - [Comments on the diagnostic principles of DSM-III exemplified by the borderline personality disorder]. AB - The first disputes around the DSM-III, which were charged with emotion and cathected by ideologies, are now followed by criticisms based on practical experience with the criteria used in the diagnostic approach of the DSM-III. The present paper is an attempt to show for the area of personality disorders, (and here in particular for borderline personality disorders) that the specific formulation of individual diagnostic questions is a contributory factor to the diagnostic assessment in this field, despite the descriptive approach of the DSM III. By comparing different item formulations for the same criterion we try to illustrate the problems involved in a purely quantitative registration of characteristics. When criteria, such as identity, interhuman relationship, etc. are concerned, subjective variables will always contribute to the diagnostic assessment. PMID- 2310622 TI - [Psychosocial factors of preserving health? Prospective studies of breast cancer, bronchial cancer and fibrocystic mastopathy]. AB - Do psychosocial factors affect the development of health? 156 patients were interviewed and tested before a breast biopsy or before the initial medical treatment of lung cancer. Multiple regressions examined the influence of age, diagnosis (tumor stage) and different psychosocial parameters as dependent variables the development of health after 2 or 5 years as independent variables. The breastbiopsy-group (n = 52) shows five psychological variables being effective in a positive (health promoting) manner: autonomy, emotional outlet, expression of one's needs, family support, lack of life stress. In lung cancer (n = 104) the development of health 2 years after diagnosis is only influenced by the type of tumor (small cell versus non small cell) and by the initial tumor stage. A structuralequation model (LISREL) shows for the first 3 months of illness that almost exclusively biological variables have an influence on psychological variables. Despite this family dynamics had a moderate effect on the patient's general wellbeing (Karnoffsky-Index). PMID- 2310623 TI - Should patients choose their anaesthetic? PMID- 2310624 TI - Sponsorship. PMID- 2310625 TI - 'MGDS examination'. PMID- 2310626 TI - 'Some parental views on the Community Dental Service'. PMID- 2310627 TI - Mercury vapour from aspirators. PMID- 2310628 TI - 'Changing perceptions of the requirements of cavity preparations'. PMID- 2310629 TI - Cracked tooth syndrome. PMID- 2310630 TI - Orthodontic research. PMID- 2310631 TI - Hours of surgery. PMID- 2310632 TI - The cost of goodwill. PMID- 2310633 TI - Veterinary wisdom. PMID- 2310634 TI - Oral medicine in practice: white patches. AB - The seventh article in this series deals with conditions of the oral mucosa which present as white patches. Although the majority of white patches are benign, certain lesions are associated with premalignancy or malignancy. Unfortunately, the presence of any sinister lesion cannot be assessed by clinical appearance and therefore accurate diagnosis (involving biopsy) is mandatory whenever there is uncertainty about the clinical diagnosis of an oral white patch. PMID- 2310635 TI - The benefit of dental care to an elderly population assessed using a sociodental measure of oral handicap. AB - The provision of dental care is based on the assumption that it contributes to quality of life. One hundred elderly people requesting dental care were interviewed and treated. Assessment was made using a sociodental index as well as clinical criteria. The index measured four categories of oral handicap (impairment of function, comfort, self-image and social interaction) prior to treatment and any benefit conferred by the treatment. Seventy-four per cent benefited from treatment. The greatest improvements were in self-image and social interaction. Function was the most difficult category to satisfy. One third of subjects whose oral function was compromised before treatment were still in this state after treatment. PMID- 2310636 TI - Oxygen saturation during general anaesthesia in the dental chair. A comparison of the effect of position on saturation. AB - Oxygen saturation was measured in 135 children requiring general anaesthesia for multiple dental extractions. These were dental chair anaesthetics administered in a community dental clinic. Sessions were assigned to either sitting or supine, producing two groups for comparison. Saturation was monitored continuously for the duration of the procedure. There was no significant difference in the saturation changes of the two groups. Experience and familiarity with working in either position in the dental chair was found to be a key factor in avoiding problems for both the anaesthetist and the operator. PMID- 2310637 TI - Treatment of Class II malocclusions with removable appliances. 1. Case assessment. AB - Successful correction of overbite and overjet after orthodontic treatment may be judged in terms of incisor overbite and inter-incisal angle. Removable appliances can produce worthwhile overbite reductions, but the final inter-incisal angle depends upon skeletal pattern. It is vital, therefore, to make an assessment of this factor when planning treatment for a Class II malocclusion. PMID- 2310638 TI - Dental health in residential and nursing homes for elderly people in the south Birmingham health district. PMID- 2310639 TI - Chewing gum and dental health--a review. AB - Recent evidence of the actions of chewing gum on plaque pH needs to be assessed against the background of other evidence, including clinical data. 'Sugar-free' gums are non-cariogenic and potentially beneficial in reversing early caries, while the potential cariogenicity of sucrose-sweetened gums can be modified by additives or selected patterns of use. PMID- 2310640 TI - Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion. AB - The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful. PMID- 2310641 TI - Left ventricular function during balloon dilatation of the aortic valve in elderly patients: a blind study of echocardiograms. AB - Subcostal echocardiography of the left ventricle was continuously recorded during balloon dilatation of the aortic valve in ten consecutive elderly patients. Left ventricular wall motion decreased gradually during a minute of maintained complete balloon inflation. Blind analysis of M mode echocardiograms showed a significant reduction in fractional shortening. Deflation of the balloon resulted in global left ventricular hyperkinesia. There was a transient overshoot in fractional shortening, wall thickness, and blood pressure approximately 40 s after deflation of the balloon. The myocardial reaction was similar to that known to occur regionally with brief coronary artery obstruction, whereas the timing of the events seemed to be dissociated from the timing of changes in left ventricular load. Thus it is likely that the left ventricular response during valve dilatation reflects not only changes in load but also an ischaemia reperfusion effect on the myocardium. The systolic thickening of the hypertrophied interventricular septum was slightly reduced after balloon dilatation. This finding might be a result of repeated episodes of ischaemia and reperfusion. However, the potential for myocardial injury seemed to be unimportant clinically. PMID- 2310642 TI - Open valvotomy for critical aortic stenosis in infancy. AB - Over a 5 year period open valvotomy was performed on 13 patients under the age of one year with critical aortic stenosis. All 13 survived operation. There were two late deaths--one 38 days after operation, associated with an unrelated neurosurgical procedure and the other 2 years 6 months after when aortic root enlargement and replacement of the aortic valve were performed. During this period two other infants presented with aortic stenosis. One, who was very ill before transfer, died before operation could be performed. The second patient had a hypoplastic left ventricle with a small mitral valve ring and was, therefore, considered to be part of a different subgroup. All the surviving children have been followed up (median length of follow up 2 years and 11 months, range 7 months-5 years). Left ventricular function, in terms of percentage systolic wall thickening, was shown to be significantly impaired in all age groups. Peak diastolic thinning was abnormal in those children aged from 3 to 5. The aortic valve gradient, as assessed by peak instantaneous continuous wave Doppler, was less than 40 mm Hg in five patients and between 40 and 70 mm Hg in seven patients. One patient, with appreciable restenosis, has undergone successful percutaneous balloon dilatation of the aortic valve. PMID- 2310643 TI - Doppler echocardiographic characteristics of normal and dysfunctioning prosthetic valves in the tricuspid and mitral position. AB - The Doppler echocardiographic characteristics of 70 prosthetic valves in 35 patients are reported. Twenty nine patients had a Bjork-Shiley prosthesis in both mitral and tricuspid positions and six had Carpentier-Edwards valves in both sites. Five of the patients had abnormal tricuspid prostheses on the basis of clinical and echocardiographic criteria. Pulsed wave Doppler echocardiography was used in all examinations. The pressure half times for the normal tricuspid prosthetic valves, 105 (40) ms (Bjork-Shiley) and 97 (53) ms (Carpentier Edwards), were significantly longer than those of normal mitral prosthetic valves, 75 (18) ms (Bjork-Shiley) and 83 (15) ms (Carpentier-Edwards). The range of pressure half times for the abnormal tricuspid valves (237-530 ms) was distinct from that of the apparently normal tricuspid prosthetic valves (38-197 ms). There was an increase in the peak velocity of the obstructed tricuspid prosthetic valves (1.69 (0.12) m/s) in comparison with normal prostheses (1.06 (0.26) m/s). The normal range of pressure half times for the Bjork-Shiley and Carpentier-Edwards valves in the mitral position is not applicable to the same valves in the tricuspid position. The valve appears to function well with very long pressure half times but a pressure half time of greater than 200 ms coupled with a peak velocity of greater than 1.60 ms without significant valve regurgitation indicates tricuspid obstruction of the tricuspid prosthetic valve. PMID- 2310644 TI - Changes in the pressure-volume relation of the right ventricle when its loading conditions are modified. AB - Ventricular pressure-volume diagrams were obtained from the right ventricle in patients before and after relief of right ventricular pressure load, in patients with volume loaded right ventricles, and from the left ventricle in patients after the Mustard procedure for transposition of the great arteries. The patterns of ejection during pressure development and decline were similar in patients after relief of pressure load and in those with isolated volume load. A right ventricular pressure load, however, reduced ejection during the two "isovolumic" periods, and the overall shape of the pressure-volume loop resembled that of the normal left ventricle. Pressure-volume diagrams obtained from the left ventricle after the Mustard procedure were indistinguishable from the normal right ventricle, which accords with the hypothesis that the normal right ventricular contraction pattern is a consequence of loading conditions rather than a reflection of an intrinsic property of the myocardium. PMID- 2310645 TI - Anomalous origin of the left coronary artery from the pulmonary trunk: elucidation with colour Doppler flow mapping. AB - Four infants and children with anomalous connection of the left coronary artery to the pulmonary trunk were studied with colour Doppler flow mapping. In three the diagnosis was only suspected when the colour Doppler study showed dilated intraseptal and epicardial vessels and an abnormal flow signal into the pulmonary artery in diastole; this latter signal localised the exact site of communication, which was not apparent on angiocardiography. Two of these patients had previously had operations for severe mitral regurgitation, the diagnosis of anomalous left coronary artery having been previously considered in one but missed despite aortic root angiography. The colour study in the fourth was largely confirmatory, operation without catheterisation being undertaken on the basis of the echocardiographic images. By contrast in two infants subsequently seen with congestive cardiomyopathy the demonstration of flow direction in the left coronary artery confirmed that it was normally connected to the aorta. Colour Doppler flow mapping can show flow direction in the left coronary artery and from the mouth of an anomalous coronary artery into the pulmonary artery, thus simplifying the diagnosis and allowing the site of the connection of the left coronary artery to the pulmonary artery to be determined with precision. PMID- 2310646 TI - Reversible impairment of myocardial function in hypoparathyroidism causing hypocalcaemia. AB - A 25 year old woman presented with severe myocardial dysfunction. Laboratory tests showed hypocalcaemia caused by hypoparathyroidism. After the restoration of normal concentrations of serum total and free ionic calcium indices of left ventricular function returned to normal and her symptoms disappeared. PMID- 2310647 TI - Arterial microembolisation: an unusual presentation of dilated cardiomyopathy. AB - Systemic embolisation is common in patients with dilated cardiomyopathy. Microembolisation as a presenting sign of dilated cardiomyopathy, however, has not been reported before. A 37 year old woman in whom dilated cardiomyopathy presented as arterial microembolisation to the toes is described. PMID- 2310648 TI - Pulmonary arterial occlusions and aneurysms: a forme fruste of Behcet's or Hughes Stovin syndrome. AB - A patient is reported with pulmonary arterial occlusions and aneurysms and recurrent haemoptysis. He gave a history of recurrent arthropathy and febrile illnesses; though he had had no other features of Behcet's or Hughes-Stovin syndrome his disease probably fell into this broad diagnostic category. PMID- 2310649 TI - Fatal intrathoracic haemorrhage after cardiopulmonary resuscitation and treatment with streptokinase and heparin. PMID- 2310650 TI - When does the risk of acute coronary heart disease in ex-smokers fail to that in non-smokers? PMID- 2310651 TI - Evaluation of exercise electrocardiography and thallium tomographic imaging in detecting asymptomatic coronary artery disease in diabetic patients. AB - Thallium tomographic imaging and exercise electrocardiography were performed on 136 diabetic patients without symptoms of heart disease. Thirty three patients had post-exercise thallium defects and 19 had ST 1 mm greater than or equal to segment depression during exercise electrocardiography. Both tests were positive in 13 patients. Coronary angiography was subsequently performed on 33 patients with either scintigraphic and/or electrocardiographic evidence of myocardial ischaemia. Angiographically significant coronary artery disease (greater than or equal to 50% narrowing of the coronary artery lumen) was detected in 13 patients. Six patients had minimal coronary artery stenosis (less than 50%), and 14 had normal coronary arteries. Six patients refused cardiac catheterisation. In 14 out of 27 patients with post-exercise thallium defects coronary angiography did not show any coronary artery stenoses (positive predictive accuracy 48%). Exercise electrocardiography showed only one false positive result (positive predictive accuracy 94%) but failed to detect coronary artery disease in three patients with a positive scintigraphic result. The accuracy of a positive exercise electrocardiographic test seems to be better than that of a positive thallium tomographic scan for detecting asymptomatic coronary artery disease in diabetic patients. The high number of false positive thallium defects may be the result of technical features inherent in thallium tomography and/or the possible disease of the small intramyocardial arteries in diabetic patients. PMID- 2310652 TI - The effects of a single dose of dilevalol on [3H]-noradrenaline plasma kinetics and plasma lipoprotein cholesterol concentrations. AB - 1. A single oral dose of dilevalol (200 mg or 400 mg) or placebo was administered to 15 normal male volunteers in a double-blind, random order crossover study. 2. Dilevalol had no significant effect on supine blood pressures or heart rates, but caused a significant fall in systolic blood pressure 1 and 30 min following standing, and attenuated the rise in diastolic blood pressure and heart rate that accompanies standing. 3. Dilevalol caused a dose dependent increase in plasma noradrenaline levels from arterialized blood which was due to an increase in noradrenaline spillover with no change in clearance. 4. Dilevalol increased plasma levels of the noradrenaline metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) (which is formed in sympathetic nerves following neuronal uptake of noradrenaline), indicating that the increase in noradrenaline spillover was not due to the blockade of neuronal uptake. 5. Acute dilevalol administration had no effect on total plasma cholesterol, HDL-cholesterol or LDL-cholesterol levels. PMID- 2310653 TI - The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. AB - 1. The oral and intravenous kinetics of morphine were investigated in seven cirrhotic patients with a history of encephalopathy. The plasma concentrations of morphine and its metabolites morphine-3 (M3G) and morphine-6 (M6G) were measured by h.p.l.c. 2. The mean terminal elimination half-life of morphine was 4.2 h (95% CI 3.6-4.8) the mean volume of distribution was 4.1 l kg-1 (95% CI 2.9-5.4) and the mean plasma clearance was 11.4 ml min-1 kg-1 (95% CI 8.1-14.7). The mean oral bioavailability was 101% (95% CI 56-147). 3. The plasma clearance of morphine was significantly lower, its terminal elimination half-life longer and its oral bioavailability greater in the cirrhotic patients compared with patients with normal liver function. The metabolic ratio M3G/morphine was significantly lower in the cirrhotic patients than in control subjects after oral dosing, but did not differ after intravenous dosing. 4. The average urinary recoveries of morphine plus M3G and M6G were 49.9% after i.v. and 57.7% after oral administration. There were no statistically significant differences in the urinary recovery between the two routes of administration or between the cirrhotic patients and controls. 5. Specific changes in the EEG pattern could not be detected after intravenous dosage. 6. The metabolism of morphine is impaired significantly in patients with severe cirrhosis. Clinically important findings were a high oral bioavailability and a long elimination half-life. These findings call for cautious dosing of oral and intravenous morphine in patients with severe end stage liver disease. PMID- 2310654 TI - A dose-effect study of the in vivo inhibitory effect of quinidine on sparteine oxidation in man. AB - 1. Twelve healthy extensive metabolisers of sparteine were sparteine tested daily for 6 days (19.00 h to 07.00 h). A small but statistically significant rise in sparteine metabolic ratio (MR) was observed. 2. Following 100 mg quinidine sulphate given to four of the subjects at 16.00 h, sparteine tests were carried out 19.00 h to 07.00 h on the same day and then daily for 6 days. Quinidine caused an immediate twenty-fold increase in sparteine-MR which then gradually returned to normal over the following 4-6 days. Quinidine concentrations in plasma were measurable only up to 20 h after the quinidine test dose. 3. At weekly intervals, all 12 subjects received single doses of quinidine sulphate of 5, 10, 20, 40 and 80 mg at 16.00 h, each time followed by a sparteine test 19.00 h to 07.00 h on the same day. A clear dose-effect relationship was found with a significant rise in the sparteine-MR even after 5 mg quinidine. After 80 mg quinidine, 8 of 12 subjects became phenotypically poor metabolisers (MR greater than 20). PMID- 2310655 TI - Effects of acetylsalicylic acid and paracetamol alone and in combination on prostanoid synthesis in man. AB - 1. The present study was designed to investigate the effects of acetylsalicylic acid and paracetamol given separately and in combination on total body and renal PGE2 synthesis in healthy volunteers. 2. In a randomized four-way cross-over study eleven female volunteers received for two consecutive days 3 g day-1 acetylsalicylic acid or 3 g day-1 paracetamol or a combination of 1.5 g day-1 acetylsalicylic acid and 1.5 g day-1 paracetamol, or 1.5 g day-1 acetylsalicylic acid separated by washout phases of at least 5 days. Urinary excretion of the major urinary metabolite of PGE2 (PGE-MUM), PGE2 and creatinine clearance were measured before and on day 2 of each treatment period. Compliance was tested by measuring metabolites of the two drugs in urine. 3. Paracetamol did not reduce urinary excretion of PGE2 whereas both dosages of acetylsalicylic acid caused a significant reduction. 4. The combination of both drugs did not reduce PGE2 excretion more than acetylsalicylic acid alone. 5. All four drug schedules reduced urinary excretion of PGE-MUM significantly. PMID- 2310656 TI - Acute haemodynamic effects of cromakalim in patients with angina pectoris. AB - 1. We studied the acute haemodynamic effects of cromakalim, a vasodilator which activates smooth muscle potassium channels, in 11 patients with ischaemic heart disease undergoing routine cardiac catheterisation. A similar group of six patients given placebo were studied under identical conditions. 2. There were no significant differences in baseline haemodynamic parameters between the two groups. 3. Following intravenous cromakalim (15 micrograms kg-1) cardiac output increased by 30% (P less than 0.05 vs placebo) while systolic arterial pressure decreased by 8% (P less than 0.05), systemic vascular resistance decreased by 29% (P less than 0.01) and pulmonary vascular resistance decreased by 24% (P less than 0.01) at plasma concentrations of the (+)- and (-)-enantiomers of cromakalim of 6.2 +/- 0.5 ng ml-1 and 10.0 +/- 1.0 ng ml-1 respectively. 4. There were no significant differences in diastolic arterial pressure, left ventricular dP/dt and stroke volume between the two groups. Heart rate increased by 11% following cromakalim but this did not achieve significance. 5. These findings confirm that cromakalim acts primarily as an arteriolar vasodilator producing an improvement in cardiac performance. Cromakalim may be of benefit in the treatment of patients with ischaemic heart disease. PMID- 2310657 TI - Development of tolerance to nifedipine in patients with stable angina pectoris. AB - 1. The possibility of development of tolerance to the anti-ischaemic and anti anginal effects of nifedipine during sustained administration for 2 months was studied in 15 patients with stable angina pectoris by means of repeated exercise tests on a treadmill. 2. After acute administration of nifedipine (20-30 mg) substantial anti-ischaemic and anti-anginal effects lasted for at least 4 h in all patients. 3. During sustained nifedipine treatment with a dose schedule which provided continuous anti-ischaemic effect during a day (mean daily dose 82.7 +/- 6.0 mg, range 60-120 mg) a substantial attenuation of this effect was registered. The duration of the anti-ischaemic effect was 5.4 +/- 0.3 h after acute administration, decreasing significantly to 3.6 +/- 0.4 h during sustained administration. 4. The attenuation of the nifedipine effect was not associated with worsening of the patients' condition. 5. Plasma concentrations of nifedipine and its metabolite were similar after acute administration and during sustained treatment. Protein binding of nifedipine also remained constant during the study. 6. There was marked interindividual variation in the degree of attenuation of the nifedipine effect during sustained administration. In five patients nearly complete loss of nifedipine efficacy was registered. Eight to ten days after stopping regular administration of nifedipine only partial restoration of nifedipine effect was observed. 7. We conclude that during sustained nifedipine administration tolerance to its anti-ischaemic, anti-anginal and circulatory effects develops in a substantial number of patients with stable angina pectoris. PMID- 2310658 TI - Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol. AB - 1. In patients with acute strokes entering a large ongoing randomised double blind controlled trial of intravenous glycerol therapy, the extent and pathogenesis of any ensuing haemolysis were evaluated using standard clinical investigations and in vitro techniques. 2. Twenty patients received 10% glycerol in saline (500 ml over 4 h on 6 consecutive days) and 15 received corresponding control treatment with saline. 3. Intravascular haemolysis was evident after the first infusion; compared with the controls the glycerol group had i) a greater mean reduction in serum haptoglobin concentration (P less than .05), and ii) a greater proportion exhibiting haemoglobinaemia (P = 0.03). 4. After 6 days of glycerol treatment, the mean reduction in haemoglobin concentration was only 0.8 g more than in controls; this difference being neither clinically nor statistically significant. 5. Glycerol therapy was not associated with haemoglobinuria, renal insufficiency or disseminated intravascular coagulation. 6. Exposure of red blood cells to 1-10% glycerol in vitro did not induce haemolysis per se; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present. 7. Whilst taking standard dosage regimes of glycerol, the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinically significant; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol. PMID- 2310660 TI - The effect of sulindac on dermal responses to bradykinin in normal subjects given an angiotensin converting enzyme inhibitor. AB - The ability of sulindac to modify the weal response to four doses of intradermal bradykinin in subjects given enalapril was tested in a double-blind cross-over study in normal volunteers. The dose-dependent increase in skin thickness after bradykinin was significantly reduced by prior administration of sulindac. Certain of the actions and adverse effects of angiotensin converting enzyme inhibitors may be due to the interaction of prostaglandins and bradykinin. PMID- 2310659 TI - Single doses of ritodrine delay orocaecal transit in patients with irritable bowel syndrome. AB - The lactulose hydrogen breath test was used to assess the effect of a single dose of the beta 2-adrenoceptor agonist ritodrine on orocaecal transit time in 11 patients (three men) with irritable bowel syndrome. Transit time (median values, range) was significantly longer (P less than 0.01) after ritodrine than after placebo (120, 50-200 vs 75, 40-100 min). Median heart rate was similar before treatments whereas the maximal increase in heart rate was significantly greater (P less than 0.01) after ritodrine than after placebo. PMID- 2310661 TI - Comparative haemodynamic effects of intravenous nisoldipine and hydralazine in congestive heart failure. AB - The acute haemodynamic effects of intravenous nisoldipine and hydralazine were compared in nine patients with heart failure. Both agents caused qualitatively similar effects, reducing both left ventricular preload and afterload, with reductions in systemic vascular resistance and increases in cardiac output. However, the effect of hydralazine was significantly greater and of longer duration than nisoldipine, and was associated with side effects in four patients. This, and previously reported data, suggests that nisoldipine may be useful in patients with ischaemia and concomitant heart failure. PMID- 2310662 TI - Papers from the French Society for Vascular Surgery--1989 meeting. PMID- 2310663 TI - Superior mesenteric artery embolism: eighty-two cases. AB - Eighty-two consecutive patients with superior mesenteric artery embolism were treated between 1966 and 1988. Abdominal pain was atypical or absent in 19 (23%) patients. Except for two instances of intraoperative embolism, emergency mesenteric arteriography was diagnostic in all cases. Seventeen patients were treated medically either because the site of embolism was peripheral, or because there were no life-threatening signs. Sixty-five patients underwent surgery, 31 for mesenteric infarction, and 34 for acute mesenteric ischemia without intestinal necrosis. Surgical treatment included 34 isolated embolectomies, 20 embolectomies associated with intestinal resection, two short segmental resections for limited necrosis of the small intestine, and nine exploratory laparotomies. Of the 34 patients operated on for acute mesenteric ischemia, 12 (35%) died. Of the 31 remaining patients operated on for intestinal infarction, 21 (68%) (p less than 0.05) died. The mean duration of ischemia before operation was 13 hours 20 +/- 6 min and 21 hours 24 +/- 24 min, respectively (p less than 0.05). Two patients (12%) receiving medical treatment died. This study confirms that survival is directly related to early diagnosis based on emergency mesenteric arteriography. Treatment is determined by clinical and roentgenographic criteria. Medical treatment is indicated in certain circumstances. PMID- 2310664 TI - Aortic reimplantation of the superior mesenteric artery for atherosclerotic lesions of the visceral arteries: sixty cases. AB - We report the results of a series of patients who had isolated or associated reimplantation of the superior mesenteric artery directly into the infrarenal aorta. Between 1967 and 1988, a total of 91 revascularizations for atheromatous lesions of the visceral arteries were performed in 89 patients. The superior mesenteric artery was reconstructed in 87 instances, 60 of which were direct or indirect reimplantations into the juxtarenal aorta. The procedure was isolated in 51 cases, and associated with the revascularization of another visceral artery in nine cases. These 60 patients were divided into three groups: Group A--seven patients undergoing emergency operation for acute intestinal ischemia; Group B- 30 patients operated upon for chronic intestinal angina; and Group C--22 asymptomatic patients who underwent prophylactic revascularization. Two patients died in the immediate postoperative period (3.5%). Although most of the 29 late deaths were due to vascular disorders, only one was secondary to intestinal infarction. Twenty-one patients followed had good functional results; six patients had relapse of abdominal pain. Three of these underwent repeat revascularization of the superior mesenteric artery 12 days, 18 months, and 22 months, postoperatively. Follow-up ranged from six months to 18 years. Two patients were lost to follow-up. Overall actuarial survival at five years was 69.60 +/- 15%. In our experience, isolated reimplantation of the superior mesenteric artery on the anterior aspect of the infrarenal aorta is a simple and reliable technique which affords good long-term results. PMID- 2310665 TI - Carotid artery endarterectomy in patients over seventy years-of-age. AB - Carotid artery endarterectomy in the elderly patient has been considered to be a high risk procedure. Recent reevaluation, however, showed that advanced age alone doesn't seem to increase the perioperative surgical risk. We retrospectively reviewed the records for 222 carotid artery endarterectomies, not combined with any other type of surgery, in 195 patients over 70 years-of-age. Twenty-eight patients (14.3%) were asymptomatic, 43% were seen after transient ischemic attacks, 5.1% after reversible ischemic neurologic defects, and 37.4% after stroke. A standard operative protocol was followed. We used a shunt in 45.5% of patients, a standard endarterectomy was performed in 93% of patients, using a patch in 68%. There were three perioperative deaths and seven perioperative strokes in the series; total combined morbidity and mortality was 5.1%. In the 73 patients operated after previous stroke, three died and five suffered a perioperative stroke; total combined morbidity and mortality was 10.9%. In the 122 patients operated after previous transient ischemic attack or asymptomatic, two suffered a perioperative stroke; total combined morbidity and mortality was 1.6%. Late survival was identical to the survival of a normal Belgian control population, and stroke and death-free ratio at five years was 65%, 52% for patients operated after previous stroke and 69% for asymptomatic patients or patients operated after transient ischemic attack. Carotid artery endarterectomy can be performed in patients over 70 years-of-age with perioperative results equal to those of younger patients. PMID- 2310666 TI - Primary closure of below-knee amputation stumps: a prospective study of sixty-two cases. AB - Between January 1, 1985, and December 31, 1988, we prospectively studied the outcome of 62 consecutive below-knee amputations with primary closure in 56 patients. There were 35 men and 21 women; mean age was 70 years. Above-knee amputation was performed for occlusion of the profunda femoris artery, acute thrombosis of a popliteal aneurysm with inadequate sural artery vascularity, intractable knee flexion contracture, suspended ischemia, and occasionally, when ischemia was found intraoperatively to extend proximally during below-knee amputation. Bedridden patients deemed unfit for prosthetic devices were also candidates for above-knee amputation. Fifty-four lower extremities (87%) were gangrenous and rest pain was present in eight patients (13%). Twenty-nine limbs (47%) were amputated primarily, 33 (53%) after failure of one or more revascularization procedures. Six patients had bilateral amputation. Forty patients (71%) were diabetic. Mean hospital stay was five days. Fifteen patients (27%) died during a mean follow-up period of 29 months. Eleven stumps (17.5%) required reoperation; five for postoperative infection, four for wound breakdown after a fall, and two for secondary abscess. Three secondary above-knee amputations (5%) were necessary. Of 44 below-knee amputations in diabetic patients, one had to be revised at the level of the thigh. Of 33 amputations after revascularization failure, one secondary above-knee amputation was necessary. Restoration of preischemic status was achieved after a mean of 58 days. Upon patient discharge from a rehabilitation center, 44 stumps (81%) were suitable to be fitted with prostheses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310667 TI - Calcified obstructive disease of the aortic isthmus. AB - A 52-year-old man presented with a calcified thrombus measuring 5 cm in length, which was responsible for obstruction of two-thirds of the aortic isthmus lumen. At operation the thrombus was seen to stem from an ulcerated plaque in the aortic wall, 4 mm in diameter. Six years later, his aortograms were normal. We believe the thrombus had an atheromatous origin. PMID- 2310668 TI - Occlusive disease of the renal arteries and chronic renal failure: the limits of reconstructive surgery. AB - In order to investigate the value of renal revascularization in patients with chronic renal failure and associated occlusive lesions of the renal arteries, the long-term results of 48 revascularizations in 43 patients operated upon between January 1980 and May 1988 were analyzed. There were 36 men and 7 women whose mean age was 61.8 years (range 36 to 79 years). The diagnosis of kidney failure was based on serum creatinine levels greater than 120 micromoles/L on two consecutive determinations. Patients were divided into four groups: Group I (23 patients) had a creatininemia between 120 and 200 mumoles/L, Group II (16 patients) between 200 and 350 mumoles/L, Group III (2 patients) between 350 and 800 mumoles/L and Group IV (2 patients) who had chronic renal failure requiring hemodialysis. Hypertension was found in 37 patients. Renal artery restoration was unilateral in 38 patients, 12 of whom had a solitary kidney. Restoration was bilateral in five patients. In 24 patients, renal artery surgery was associated with reconstruction of the infrarenal aorta. Three patients undergoing associated aortic procedures (7%) died after surgery. Thirty-nine patients were followed for a mean of 35.1 months; one patient was lost to follow-up. Improvement or stabilization of renal function was noted in 24 patients (62%). Deterioration was found in 15 patients (38%), six of whom presently required chronic hemodialysis. In Groups I and II, 69.5% of patients stabilized or improved their kidney function. Renal function worsened in all patients in Groups III and IV. We conclude that restorative renal surgery can improve renal function in patients whose preoperative serum creatinine levels are less than 350 mumoles/L. In this population of patients, associated aortic restoration should be performed only when absolutely necessary. PMID- 2310669 TI - The use of infrared laser therapy in the treatment of venous ulceration. AB - Management of intractable venous ulceration remains an unrewarding task which is increasingly delegated to the realm of the vascular surgeon. The purpose of this pilot study was to assess the ulcer-healing effects of the newest form of biostimulation--the low power laser. Twelve patients with chronic venous ulcers unresponsive to conservative measures were treated with infrared laser irradiation for twelve weeks. Two ulcers healed completely and there was a 27% (p less than 0.01) reduction in size of the remaining ulcers. Treatment resulted in a 44% (p less than 0.01) increase in ulcer floor area occupied by healthy granulation tissue. The most dramatic effect of laser treatment was the reduction in ulcer pain, from 7.5 to 3.5 (linear analogue scale) (p less than 0.001). Laser irradiation had no effect on TcPO2, number of skin capillaries or pericapillary fibrin deposition in the lipodermatosclerotic area around the ulcer. The results of this pilot study are encouraging and a carefully controlled randomized study is indicated to compare low power laser irradiation to conventional treatment in the management of venous ulcers. PMID- 2310670 TI - Traumatically-induced embolus to the hand from a thrombosed PTFE vascular access graft. AB - We report a case of a traumatically-induced embolus from a thrombosed PTFE vascular access graft in a patient who had undergone a successful cadaveric renal transplant. Although usually thought to be without subsequent sequelae, thrombosed PTFE grafts can be a source of emboli to the hand in active young patients. Diagnosis, etiology, and management are discussed. Therapeutic intervention includes exclusion of the graft from the arterial circulation to the hand and removal of all existing thrombus. PMID- 2310671 TI - Basic data related to cardiac testing and cardiac risk associated with vascular surgery. PMID- 2310672 TI - The effects of laser energy on the arterial wall. AB - Laser energy has been proposed as a method of resecting atherosclerotic plaque since the mid 1960s. However, only over the past several years have we come to understand some of the unique interactions of the laser with cardiovascular tissue. In laser angioplasty a major challenge has been choosing the optimal laser and duration of laser exposure to achieve adequate resection of plaque, while minimizing such complications as thrombosis, perforation, embolization, aneurysm formation, and accelerated atherosclerosis. Ultimately we must develop a more selective laser that resects plaque while leaving adjacent arterial wall uninjured. This review describes the physics of laser energy, the different lasers available for use in the cardiovascular system, laser-arterial wall interactions, and some of the limitations of laser angioplasty. PMID- 2310673 TI - Selection of HTLV-I positive clones is prevented by prostaglandin A in infected cord blood cultures. AB - Type A prostaglandins (PGA1 and 16,16-dimethyl-PGA2-methyl ester) were found to block the proliferation of HTLV-I infected cord blood lymphocytes (CBL) in vitro, thus preventing the clonal immortalisation that is considered as a predisposing condition to HTLV-I positive leukaemia. PGA1 and di-M-PGA2 did not affect the long-term survival of normal non-infected CBL, whereas they suppressed the proliferation of an established cord-blood derived HTLV-I positive cell line, MT 2. As shown by the number of HTLV-I infected p19+ cells, the block of the selection of immortalised, infected clones by PGAs did not appear to be due to an inhibition of early stages of HTLV-I infection. The possibility that the effect of PGAs could be mediated by an action on the immune response was also examined. PGAs regulated the cell-mediated cytotoxic function of CBL to a different extent when normal non-infected or HTLV-I exposed CBL were compared. In fact, PGAs down regulated the natural killing and macrophage/lymphocyte cytotoxic response of normal CBL, whereas they did not modify the already depressed immune response of CBL challenged with HTLV-I. These results suggest that the protective effect of PGAs against HTLV-I infection in vitro is mostly related to the direct suppression of the clonal expansion of virus-infected cells, rather than to the anti-viral activity or modulation of the cell-mediated immunity. PMID- 2310674 TI - Preliminary observations on the microdistribution of labelled antibodies in human colonic adenocarcinoma xenografts: relevance to microdosimetry. AB - Autoradiography with 125I-labelled antibodies 17-1-A and 11-285-14 (anti carcinoembryonic antigen) injected singly or together into nude mice carrying two distinct human colorectal cancer xenografts delineates marked changes in distribution and retention of isotope over 72 h, which are relevant to microdosimetry. The antibodies localise independently at low concentrations. Slow accumulation and retention predominantly in membranes of glands and necrotic areas suggest that therapy will succeed best with isotopes whose range, half-life and/or mode of delivery can exploit optimally the greater selectivity of the late retention. PMID- 2310675 TI - Immunoscintigraphy of human lung squamous cell carcinoma using an iodine-131 labelled monoclonal antibody (Po66). AB - Monoclonal antibody (McAb) Po66 has been obtained by immunisation of mice against a human lung squamous cell carcinoma. The in vitro reactivity of the antibody with cancer cells and its ability to localise in human lung cancer xenografts growing in nude mice have been reported earlier. Presented here is the first clinical evaluation of the antibody for scintigraphic detection of tumours. Thirty-three patients with histologically confirmed primary non-small cell lung carcinoma were investigated. Twenty-seven of them were explored at the preoperative stage and six at 6 months after surgery. Biodistribution results were obtained from seven operated patients by combining injections of 131I radiolabelled Po66 and of 125I-labelled unrelated immunoglobulin. The localisation index was three times higher for this specific antibody. Immunoscintigraphy detected 78% of primary tumours and 100% of recurrences. In this short series of patients, immunoscintigraphy proved helpful in the assessment of tumour spread in four patients by visualising localisations in the mediastinum or the contralateral lung which the CT scan had failed to demonstrate. Immunoscintigraphy was also more efficient than plain chest X-ray for the detection of local tumour recurrences. PMID- 2310676 TI - The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma. AB - The regional distribution of blood flow to the LBDS1 fibrosarcoma, transplanted into the subcutaneous site in rats, was investigated using the readily diffusible compound 14C-iodo-antipyrine (14C-IAP). Quantitative autoradiography was used to establish absolute values of specific blood flow F for 100 X 100 X 20 microns adjacent tissue volumes of the unperturbed tumour. Mean blood flow to whole tumours was found to decrease with increase in tumour size. This relationship was abolished if blood flow was only measured in sections cut from the periphery of the tumours. Detailed analysis of a sub-group of tumours showed that blood flow to individual tumours was heterogeneous. The range of blood flow was large, indicating that mean blood flow to a whole tumour is a poor reflection of the blood perfusion pattern of that tumour. Necrotic tumour regions were usually very poorly perfused. With the exception of the smallest tumours studied, blood flow was lower in the centre of tumours than in the periphery. Necrosis also tended to develop centrally. However, the peripheral to central gradient of blood flow was apparent even when densely cellular, viable tumour regions and necrotic regions were analysed separately. The decrease in blood flow with tumour size was also apparent in densely cellular, viable tumour regions when analysed separately. Qualitative comparison of tumour histology and regional blood flow showed that there were areas of very low blood flow associated with viable tumour regions. Less common were areas of rather high blood flow associated with necrotic tumour regions. A complicated relationship exists between tumour histology and blood flow. The quantitative autoradiography technique is suitable for investigating the most poorly perfused and the most well perfused viable fractions of animal tumours which may limit the efficacy of different types of therapy. PMID- 2310677 TI - 31P-NMR spectroscopy and histological studies of the response of rat mammary tumours to endocrine therapy. AB - We have shown by 31P-NMR spectroscopy that ovariectomy, in N-methyl-N-nitrosourea induced mammary adenocarcinomas, increases signals from phosphocreatine (PCr) relative to nucleoside triphosphate (NTP) before measurable regression (2 days) and for at least a further 13 days. The present study correlates the NMR changes with histological changes in the regressing tumour. Mammary tumours were examined by NMR before, and 2 and 14 days after, ovariectomy or sham-ovariectomy. Sections were taken from five tumours at each time point after operation for histology and for immunocytochemical staining of myoepithelial cells, luminal cells and basement membrane material. The histology showed typical cribriform papillary type mammary adenocarcinomas. The luminal cell population had a high mitotic activity and there was a prominent myoepithelial layer. At 2 days post ovariectomy no significant change in mitotic activity was observed and no cytological characteristics attributable to ovariectomy could be seen. At 14 days postovariectomy the tumour was indistinguishable from a tubular adenoma, had significantly reduced mitotic activity, a relative increase in myoepithelial cells and basement membrane material. The changes detected by NMR must reflect early metabolic events, perhaps related to the histological changes observed at 14 days after ovariectomy. 31P-NMR spectroscopy may permit early monitoring of endocrine therapy for mammary cancer. PMID- 2310679 TI - The 5T mouse multiple myeloma model: absence of c-myc oncogene rearrangement in early transplant generations. AB - Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM), arising spontaneously in the ageing C57BL/KaLwRij mice, was investigated in order to see whether the MM cells contain c-myc abnormalities of the MPC or RIC type. Rearrangement of the c-myc oncogene was found in the bone marrow cells only in 5T2 MM transplantation line in a mouse of the 24th generation and in none of the seven other MM of the 5T series which were of earlier generations. Since the mouse 5T MM resembles the human MM very closely, including the absence of consistent structural c-myc oncogene abnormalities, it can serve as a useful experimental model for studies on the aetiopathogenesis of this disease. PMID- 2310678 TI - The anchorage-dependent and -independent growth of a human SCC cell line: the roles of TGF alpha/EGF and TGF beta. PMID- 2310680 TI - Effect of n-3 fatty acids on spontaneous and experimental metastasis of rat mammary tumour 13762. PMID- 2310681 TI - Breast cancer screening: its impact on clinical medicine. AB - Breast cancer screening is generally accepted as an effective means of reducing breast cancer mortality in post-menopausal women. In this analysis the impact of nationwide screening on clinical medicine and the effects for the women involved are quantified. Effect estimates are based on results from screening trials in Utrecht (DOM-project) and Nijmegen, and on bi-annual screening of women aged 50 70. The consequences for health care are based on generally accepted assessment and treatment policies. The number of assessment procedures for non-palpable lesions will increase by 12% per year in the build-up period, and will remain slightly higher. The total number of biopsies in a real population is expected to decrease. Screening will lead to a shift in primary treatment modalities, as 15% of mastectomies will be replaced by breast conserving therapy. The temporary increase in the demand for primary treatment in the first years will be followed by a decrease in the demand for treating women with advanced disease. Favourable effects outweigh the inevitable unfavourable effects, with high quality screening and an appropriate invitation system. Breast cancer screening can also be recommended after considering other consequences than mortality reduction. PMID- 2310682 TI - Oestrogen binding and risk factors for breast cancer. AB - Although women with breast cancer tend to have a greater proportion of their circulating oestradiol non-protein bound and albumin bound, and less SHBG-bound, than controls, it remains uncertain whether this has an aetiological role or is an effect of the tumour. Oestradiol and its binding to serum proteins was investigated: (a) in relation to risk factors for breast cancer in a normal population; (b) in women with proliferative benign breast disease as a risk group for breast cancer, and women with non-proliferative benign breast disease as a low risk group, as well as breast cancer patients. The strongest associations were with body mass index; the greater the body mass the greater the bioavailability of oestradiol. Changes in relation to age at menarche and menopause could have been a function of body mass. An interesting change with age was noted with a fall in bioavailability over the menopausal years. There was no relationship apparent for parity, age at first full term pregnancy, family history or country of birth. Similar differences in oestradiol binding between cases and controls were seen for patients with breast cancer, benign epithelial hyperplasia and fibrocystic disease without proliferative changes, but these were not significant. This study provides limited support for the concept that oestradiol binding has an aetiological role in the development of breast cancer. PMID- 2310683 TI - Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. AB - Lumbar bone mineral density (BMD) determination by dual photon absorptiometry was used to study the influence of adjuvant chemotherapy for premenopausal breast cancer on the risk of premature osteoporosis. Six cycles of combination chemotherapy caused ovarian failure in 31 of 44 (71%) women, amenorrhoea mostly already beginning during treatment. In contrast, only seven of 44 (16%) women, who were pair-matched for age and year of breast cancer surgery and had not been treated with chemotherapy, were post-menopausal at the time of measurement. The mean interval after breast surgery was 3.5 years. The significantly decreased BMD in the treated group (1.17 compared to 1.29 g cm-2) could only be explained by the high incidence of menopause in these women, which on average occurred 10 years prematurely. Extrapolation of these findings suggests that adjuvant chemotherapy may precipitate osteoporotic fractures by some 10 years in a considerable proportion of women cured of premenopausal breast cancer. PMID- 2310684 TI - Tumour-associated trypsin inhibitor (TATI) and cancer antigen 125 (CA 125) in mucinous ovarian tumours. AB - A tumour-associated trypsin inhibitor (TATI) and the cancer antigen 125 (CA 125) were measured pre- or peroperatively in 30 patients with mucinous ovarian tumours (10 malignant, two borderline and 18 benign) to investigate the separate and combined use of the two markers as a diagnostic tool. In the malignant and borderline cases considered as a whole, TATI was elevated in 83% and CA 125 in 50%. The former marker was increased in one (6%) benign tumour and the latter in another (6%). The combined use of TATI and CA 125 ensured diagnosis of all malignant and borderline tumours. The specificity was 89% and the positive predictive value 86%. In conclusion, in the distinction of malignant and borderline mucinous ovarian tumours from benign ones TATI was a more reliable tumour marker than CA 125. The combined use of TATI and CA 125 ensured diagnosis of all malignant and borderline tumours in the present series. PMID- 2310685 TI - Lung cancer and passive smoking. PMID- 2310687 TI - Li-Fraumeni syndrome: a case report from Italy. PMID- 2310686 TI - Spinal seeding in cranial germinoma. PMID- 2310688 TI - A 'family clinic' for information exchange in an oncology unit. PMID- 2310689 TI - DNA flow cytometry of breast cancer fine needle aspirates. PMID- 2310690 TI - Interferon-alpha-induced morphological changes of megakaryocytes: a histomorphometrical study on bone marrow biopsies in chronic myeloproliferative disorders with excessive thrombocytosis. AB - Interferon(rIFN)-alpha, a successful therapeutic agent in the control of thrombocytosis, has been shown to suppress human megakaryopoiesis. We investigated bone marrow biopsies from 12 patients with thrombocytosis due to chronic myeloproliferative disorders. Prior to treatment as well as during rIFN alpha-2c therapy, several morphometric parameters of megakaryopoiesis were evaluated. Megakaryocyte density decreased significantly in all patients, megakaryocyte size decreased in polycythaemia vera, agnogenic myeloid metaplasia, and essential thrombocythaemia, but increased in chronic myeloid leukaemia. The various changes observed during therapy indicate an inhibitory effect of rIFN alpha-2c on megakaryopoiesis and suggest a selective influence on megakaryocytes at various stages of maturation. Increased numbers of pyknotic (bare) nuclei may reflect a shortening of megakaryocyte life-span. No remarkable changes were found in the fibre content of the bone marrow. PMID- 2310691 TI - Molecular heterogeneity of beta-thalassaemia in the Japanese: identification of two novel mutations. AB - Five unrelated Japanese beta-thalassaemia genes, from one homozygote and four heterozygotes, have been systematically characterized using DNA polymorphism analysis, polymerase chain reaction, dot-blot hybridization and direct sequencing of amplified genomic DNA. Four different molecular defects were observed on three different beta-globin gene frameworks. One of these, the A----G mutation in the TATA box, a previously described mutation, was detected by dot-blot hybridization in one homozygote and one heterozygote with the beta-globin gene of framework 2. The second mutation is a C----T substitution at position 654 of IVS-2, the mutation commonly found in Chinese, which was associated with the framework 1 gene. Another two mutations, both associated with framework 3 genes, are novel ones; an amber mutation in codon 90 (GAG to TAG) and a frameshift (+G) insertion in codon 54, both of which cause a beta 0-thalassaemia phenotype by premature termination of the beta-globin chain synthesis. PMID- 2310692 TI - Paroxysmal nocturnal haemoglobinuria with coexisting deficiency of the ninth component of complement: lack of massive haemolytic attack. AB - A 47-year-old woman with paroxysmal nocturnal haemoglobinuria (PNH) was found to have an inherited deficiency in the ninth complement component (C9). In complement-sensitivity lysis tests, 80% of her erythrocytes were markedly complement-sensitive (PNH-III). Laser cytofluorimetry with a monoclonal antibody against decay-accelerating factor (DAF) revealed that 95% of her erythrocytes were DAF-negative. Surprisingly, she has suffered only mild haemolysis and has never experienced massive spontaneous haemolysis. Gross haemoglobinuria and jaundice occurred only after receiving postoperative transfusion of whole blood. In her serum, C9 was not detectable either by immunological or by functional assays. Both the Ham test and the sugar water test using normal human serum or plasma yielded marked haemolysis of the patient's erythrocytes. When the patient's serum or plasma was used, only a trace of lysis was detected. Addition of purified human C9 to her plasma fully restored haemolysis. These observations indicated that C9 may play a critical role in haemolytic attacks in patients with PNH and that characteristic haemolysis in PNH may be tempered by coexisting C9 deficiency. PMID- 2310693 TI - Adoptive transfer of hyperthyroidism and autoimmune thyroiditis following allogeneic bone marrow transplantation for chronic myeloid leukaemia. PMID- 2310694 TI - Complete remission of autoimmune thrombocytopenia after extirpation of a benign adenofibroma of the ovary. PMID- 2310695 TI - The position of the M-BCR breakpoint does not predict the duration of chronic phase or survival in chronic myeloid leukemia. AB - It has been reported that patients with chronic myeloid leukemia (CML) with 5' breakpoints within the major breakpoint cluster region (M-BCR) of the BCR gene have somewhat better prognoses than those with 3' breakpoints. We studied the position of the breakpoint in 67 patients with CML in chronic phase using conventional Southern blotting. Using restriction enzymes BglII, BamHI and HindIII and two genomic probes, a 0.6 kb (3' M-BCR) probe hybridizing to a part of the intron between exons b3 and b4 and a 2.0 kb (5' M-BCR) probe hybridizing to sequences including exon b1, we localized the breakpoint in M-BCR as occurring 5' (n = 38) or 3' (n = 28) of the HindIII restriction site located just downstream of exon b3. We failed to localize the breakpoint in one patient. The median durations of chronic phase (37 versus 44 months respectively) and of survival (50 versus 51 months respectively) for patients with 5' and 3' breakpoints were not significantly different. When we analysed only patients whose DNA was collected within 4 weeks of diagnosis (5' breakpoints, n = 30; 3' breakpoints, n = 19), there was again no significant difference in duration of chronic phase or survival. The median survivals of patients divided into good, intermediate and poor prognosis categories in accordance with the prognostic index developed by Sokal and colleagues were 54, 50 and 26 months respectively. This study confirms the value of the Sokal prognostic index but provides no support for the notion that the precise genomic position of the breakpoint in M BCR correlates with prognosis. PMID- 2310696 TI - Two types of acquired idiopathic sideroblastic anaemia (AISA) AB - On cytological bone marrow examination we distinguished between pure sideroblastic anaemia (PSA), which is confined to dyserythropoiesis, and refractory anaemia with ring sideroblasts (RARS), which is characterized by additional dysplastic features of granulopoiesis and/or megakaryopoiesis. In a follow-up study of 94 patients with AISA diagnosed according to FAB criteria for myelodysplastic syndromes we found a striking difference in the risk of leukaemic transformation between PSA and RARS (5 year cumulative rate 1.9% v. 48%). Overall survival was much better in PSA than in RARS (5 year cumulative chance 69% v. 19%). Infections and haemorrhages were frequent causes of death in RARS but not in PSA. Bone marrow culture studies (CFU-GM) were performed on 10 consecutive patients with PSA and RARS, respectively. RARS patients showed grossly impaired colony growth, typical of the myelodysplastic syndromes. Patients with PSA had persisting colony formation, even if moderately decreased in frequency, with numbers of CFU-GM being inversely correlated with the degree of erythroid hyperplasia in the bone marrow. We conclude that on cytomorphological grounds AISA can be divided into pure (dyserythropoietic) sideroblastic anaemia (PSA) and a true myelodysplastic form (RARS), with both types differing considerably in terms of survival, risk of leukaemic transformation and findings on bone marrow culture (CFU-GM). PMID- 2310697 TI - Favourable outcome of patients older than 40 years of age after transplantation with marrow grafts depleted of lymphocytes by counterflow centrifugation. AB - Nineteen patients with a median age of 43 years (range 40-48) were transplanted for acute myelogenous leukaemia (AML), refractory anaemia with excess of blasts in transformation (RAEBt), acute lymphoblastic leukaemia (ALL) in first complete remission, multiple myeloma, and chronic myelogenous leukaemia (CML) in chronic or accelerated phase. Their outcome was compared with that of 35 patients with a median age of 34 years (range 30-39), and a group of patients with age younger than 30 years (median 24; range 16-29) transplanted for the same indications. Donors were human leucocyte antigen (HLA)-identical, mixed lymphocyte culture (MLC) negative siblings. All marrow grafts were depleted of lymphocytes by counterflow centrifugation. The estimated event-free survival at 3 years after allogeneic bone marrow transplantation was 60.7% for patients with age greater than 39 years, 57.8% for patients with age less than 30, and 43.0% for the intermediate age group (P greater than 0.3). The estimated transplant-related mortality showed no tendency to increase with older age of recipients. The incidence of acute GVHD greater than grade 1 was 15.7% in patients with age greater than 39 years, 9.5% in patients younger than 30 years, and 23% in the intermediate age group. The incidence of chronic GVHD was higher in the older patients (39% compared to 24% in patients younger than 30 years, 19% in the intermediate age group). Chronic GVHD resolved completely in five out of seven patients aged 40 years or more. Reduction of the incidence of acute graft-versus host disease by physical lymphocyte depletion allows allogeneic bone marrow transplantation for patients aged 40-50 years without increase of transplant related mortality resulting in similar event-free survival in patients older than 40 years compared to those younger than 40 years. PMID- 2310698 TI - A new human plasma cell line, Karpas 620, with translocations involving chromosomes 1, 11 and 14. AB - We report here the establishment of a new cell line, Karpas 620 (K620), from the peripheral blood of an elderly woman with an IgG-kappa plasma cell leukaemia (PCL). The line has the same hypotetraploid karyotype as the fresh cells from the patient. The cultured cells have the ultrastructural appearance of plasma cells with abundant rough endoplasmic reticulum (RER) and secrete kappa light chain. They are positive for surface antigens HLA DR, and WR17 (CD 37) and negative for CD1, CD3, CD4 and CD8. Using high resolution (HR) cytogenetic analysis it has been possible to identify all the marker chromosomes including several rearrangements commonly seen in malignancies of B cell lineage. These are a 14q+ marker with a typical 'Burkitt' morphology der(14)(pter----q32.3::8q24.1----qter) but with no reciprocal 8q-, and three translocations involving chromosome 11 at q13 with partners other than chromosome 14, namely 1q32.1, 8q24.22 and 13q14.3. An earlier report of molecular studies on the DNA of K620 has shown a rearrangement near the region on 11q13 designated BCL-1 (Rabbitts et al. 1988). This is the first report of a rearrangement in the region of 11q13 in a cell line originating from a case of plasma cell leukaemia. PMID- 2310699 TI - Antithrombin III and procoagulant activity: sex differences and effects of the menopause. AB - Among participants in the Northwick Park Heart Study, antithrombin III activity was lower in pre-menopausal women than in men of the same age. In the women, however, the menopause was associated with a significant increase in antithrombin III, mean levels in these older women then exceeding levels in men of the same age. The occurrence of the menopause was also accompanied by large increases in factor VII coagulant activity, VIIc, and in plasma fibrinogen, these increases being greater in those experiencing a natural menopause than in those whose menopause was artificial. Sex differences in antithrombin III may form part of the explanation for the observed differences between men and women in their experience of ischaemic heart disease (IHD) and also for the contrasting effects of oral contraceptives and of hormone replacement therapy on the risk of thromboembolic disease. PMID- 2310700 TI - Effect of warfarin on plasma concentrations of vitamin K dependent coagulation factors in patients with stable control and monitored compliance. AB - There is a discrepancy in the results of reported studies of levels of vitamin K dependent coagulation factors in patients on warfarin therapy. This may have arisen partly because of the problem of assuring compliance with therapy in outpatients. The plasma concentrations of the vitamin K dependent clotting factors II, VII, IX and X were studied in 23 outpatients whose adherence to prescribed warfarin therapy was determined using a pharmacological indicator of compliance. In these patients, who were shown to have consistently good compliance and stable anticoagulant control over a period of 3-6 months, the activities in plasma of the four coagulation factors were not equally suppressed. Factor IX levels were significantly greater than those of factor VII (P less than 0.0001) which in turn were significantly greater than the levels of factor II (P less than 0.0001) or factor X (P less than 0.0001). There was no significant difference between the levels of factors II and X which were depressed to a similar extent. The proportion of variability of the International Normalized Ratio (INR) explained by linear regression was 51-77% and a model was derived to predict the INR from the mean of the levels of the four clotting factors. The concentrations of the coagulation factors II, VII, IX and X are likely to be highly dependent on the degree of compliance with warfarin therapy which should be taken into account when investigating the behaviour of these factors. PMID- 2310701 TI - Direct activation of platelets by heat is the possible trigger of the coagulopathy of heat stroke. AB - The trigger of the coagulopathy that complicates heat stroke is obscure, but direct platelet activation by heat is a possibility we set out to study. Platelet rich plasma (PRP), prepared from blood donors, was incubated at increasing temperatures (38-45 degrees C) and then platelet aggregation was undertaken in response to decreasing low doses of ADP (less than 2.0 mumol/l). Hyperaggregability was manifested when the incubation temperature reached 43 degrees C and was maximum at 44 degrees C before complete inhibition of responses at 45 degrees C. The platelet hyperactivity induced by heating at 44 degrees C persisted after reincubating PRP samples at 37 degrees C. These platelet responses could not be triggered in PRP samples prepared from subjects after the overnight ingestion of aspirin or after the addition of aspirin to PRP before starting the heating procedure. However, aspirin was less effective when added to PRP after the appearance of the heat-induced hyperaggregability. In conclusion, these results indicate that platelets can be activated directly by heat. This mechanism which may be operational in heat stroke, is unaffected by cooling (body cooling being basic in the management of heat stroke) but can be prevented by the early administration of aspirin. PMID- 2310702 TI - Receptor-ligand complexes are cleared to the open canalicular system of surface activated platelets. AB - Human platelets were incubated with gold particles coupled to fibrinogen to label the glycoprotein IIb-IIIa (GPIIb-IIIa) receptor after initial activation of the cells by contact with formvar-coated grid and glass surfaces. Fibrinogen-gold (Fgn-Au) markers were absent on discoid platelets, but diffusely spread over the surface and extended pseudopods of early dendritic cells. Conversion to spread platelets resulted in movement of ligand-receptor complexes away from the cell margin toward cell centres. However, Fgn-Au gold did not concentrate in the central region. Rather, the Fgn-Au, GPIIb-IIIa complexes in the middle of spread platelets appeared to move toward a belt-like, intermediate zone, as did the ligand receptor complexes from the cell margin and pseudopods. The ultimate destination of the mobile receptor-ligand complexes, however, appeared to be channels of the surface-connected open canalicular system (OCS). Fgn-Au was concentrated in OCS channels of most dendritic and a small proportion of spread platelets. The decreased frequency of Fgn-Au filled channels in more transformed platelets may have been due to collapse or evagination of the OCS. Examination of platelets exposed to Fgn-Au after spreading on glass and then prepared for thin sections confirmed that the OCS was the final destination for mobile ligand receptor complexes on surface-activated platelets. Findings of this study are consistent with previous work showing clearance of mobile receptor-ligand complexes to the OCS of platelets activated in suspension. PMID- 2310703 TI - Incidence of cancer among ferrochromium and ferrosilicon workers: an extended observation period. AB - Results are presented of a cohort study on the incidence of cancers and crude death rates in ferrochromium and ferrosilicon workers. The whole cohort was observed from 1 January 1953 to 31 December 1985. Two sets of results are presented; one restricted to workers first employed before 1960 and one to workers first employed before 1965. The latter cohort consists of 1235 workers. The total mortality in the whole cohort was low (SMR = 81) as was the overall incidence of cancers (SIR = 84). There was an overall deficit of deaths and cases of cancer in the ferrosilicon group. An excess of lung cancer (SIR = 154) and cancer of the prostate (SIR = 151) was observed in the ferrochromium workers employed before 1965. Cancer of the kidney was also in excess (SIR = 273) in the ferrochromium group, with a mean "latency time" of 39 years. Two cases of malignant melanomas had occurred versus 0.19 expected in a small subgroup of workers in electrical shops and an electric power station. PMID- 2310705 TI - Inhaled particle deposition and body habitus. AB - As a result of the intrapleural pressure gradient that exists in the human lung, both ventilation and particle deposition increase from apex to base. Since the intrapleural gradient varies with the height of the subject, it was decided to compare regional particle deposition in tall, short, and obese subjects to ascertain whether it was influenced by height and weight. Surprisingly, deposition in the vertical plane was not significantly influenced by the height of the subject when corrected for ventilated lung volume. In addition, it was shown that in obese subjects there was increased deposition in the middle zones relative to the apices and bases. This finding persisted after correction for ventilated lung volume and differential attenuation resulting from non-uniform thickness of the fat layer in the obese subject's chest. In the tall and short groups there was a consistent pattern in the concentric deposition of particles with there being a gradient from the central or hilar region to the periphery of the lungs, with the latter showing the most deposition. PMID- 2310704 TI - Stress at work and mental health status among female hospital workers. AB - Relations between working conditions and mental health status of female hospital workers were studied in a sample of 1505 women: 43% were nurses, 32% auxiliaries, and 7% ancillary staff; 13% were other qualified health care staff, mainly head nurses; 5% had occupations other than direct health care; 63% worked on the morning, 20% on the afternoon, and 17% on the night shift. Data were collected at the annual routine medical visit by the occupational health practitioner, using self administered questionnaires and clinical assessments. Five health indicators were considered: a high score to the general health questionnaire (GHQ); fatigue; sleep impairment; use of antidepressants, sleeping pills, or sedatives; and diagnosis of psychiatric morbidity at clinical assessment. Four indices of stress at work were defined: job stress, mental load, insufficiency in internal training and discussion, and strain caused by schedule. The analysis was conducted by multiple logistic regression, controlling for type of occupation, shift, number of years of work in hospital, daily travel time to work, age, marital status, number of children, and wish to move house. Sleep impairment was mostly linked to shift and strain due to schedule. For all other indicators of mental health impairment and especially high GHQ scores, the adjusted odds ratios increased significantly with the levels of job stress, mental load, and strain due to schedule. This evidence of association between work involving an excessive cumulation of stress factors and mental wellbeing should be considered in interventions aimed at improving the working conditions of hospital workers. PMID- 2310706 TI - Inhibition of creatine kinase activity by ethylene oxide. AB - Exposure of rats to 500 ppm ethylene oxide for six hours a day, three times a week, for 12 weeks, lowered serum creatine kinase activity by more than 40%. The only other change was a slightly decreased triglyceride concentration. After four weeks of exposure, neither aspartate aminotransferase nor lactate dehydrogenase activity in brain, spinal cord, and muscle was affected but creatine kinase activity was clearly inhibited. In vitro, ethylene oxide inhibited creatine kinase activity in brain homogenate and in a purified muscle enzyme preparation. Dithiothreitol did not counteract the effect of ethylene oxide. Though the amount of sulphydryl groups in purified creatine kinase was decreased considerably by exposure to ethylene oxide, the enzyme still showed moderate activity. Thus ethylene oxide inhibits creatine kinase activity in vivo and in vitro and the inhibition appears to be unrelated to the disruption of sulphydryl groups in the enzyme. PMID- 2310707 TI - Analysis of chromosomal aberrations in workers exposed to low level benzene. AB - Metaphase chromosome preparations were analysed as part of a larger study from a population occupationally exposed to benzene and compared with a control group. Forty eight of the 66 exposed individuals and 29 of the 33 controls had samples in which metaphase spreads could be evaluated. The incidence of chromosomal aberrations (particularly chromatid deletions and gaps) in the exposed group were slightly increased compared with the control group. This increase was of borderline significance in parametric statistical tests but was significant using Fisher's exact test. No lifestyle factors had any consistent effect on the incidence of chromosome aberrations, although there was a small reduction in gaps with increasing cigarette smoking. Older individuals had a higher incidence of chromosome exchanges and "other" aberrations. Individuals who reported a recent viral illness had a higher incidence of aberrations particularly gaps. There was no evidence of any correlation in the incidence of chromosome aberrations with any of the other biological parameters previously reported. The increased incidence of aberrations seen in the group exposed to benzene may result from a history of exposure to benzene. Nevertheless, other explanations such as sampling, interindividual variability, and unintentional bias in the selection of two groups cannot be excluded. PMID- 2310708 TI - Exposure to toluene increases the urinary excretion of D-glucaric acid. AB - Workers at a printing plant exposed to low concentrations of toluene (43-401 mg/m3, median 155 mg/m3) had increased urinary D-glucaric acid (3.55-5.12 mmol/mol creatinine) excretion at the end of the shift compared with controls (2.45-3.35 mmol/mol creatinine). No increase was found after the summer holiday (1.92-2.89 mmol/mol creatinine) but excretion had increased two weeks later (4.05 5.55 mmol/mol creatinine). These changes in the excretion of D-glucaric acid were not correlated to levels of exposure, to changes of urinary hippuric acid and o cresol half lives (three to eight hours), nor to o-cresol/hippuric acid concentration ratios when measured at the end of daily exposure. Since a significant intra and interindividual variability of urinary D-glucaric acid was found in all groups, urinary D-glucaric acid excretion is suitable to monitor group but not individual exposure. PMID- 2310709 TI - Liquid/air partition coefficients of four terpenes. AB - The liquid/air partition coefficients of four common terpenes, alpha-pinene, beta pinene, 3-carene, and limonene, have been determined in vitro using head space technique. The liquids used were water, human blood, and olive oil. alpha-Pinene, beta-pinene, and 3-carene were practically insoluble in water and limonene was slightly soluble; all were readily dissolved in olive oil. The oil/air partition coefficients ranged from 2900 to 5700 in the order alpha-pinene, beta-pinene, 3 carene, and limonene. The blood/air partition coefficients ranged from 15 to 42 in the same order as for oil/air. PMID- 2310710 TI - Cutaneous haemangioendothelioma: a possible link with chronic exposure to vinyl chloride. AB - A patient who worked with polyvinyl chloride developed a malignant haemangioendothelioma of a toe. This rare tumour is more commonly found in the liver where it has been reported to arise in association with exposure to the vinyl chloride monomer. PMID- 2310711 TI - Pleural mesothelioma in a non-shipyard electrician. PMID- 2310712 TI - Sedentary work in middle life and fracture of the proximal femur. PMID- 2310713 TI - Cancer mortality in a northern Italian cohort of rubber workers. PMID- 2310714 TI - Effects of low exposure to inorganic mercury on psychological performance. AB - The effects of low exposure to inorganic mercury on psychological performance was investigated: the study groups included eight chronically exposed workers and 20 who were only occasionally exposed. These were compared with a control group of 22 subjects from the same plant who were not exposed to mercury. All subjects were administered the WHO test battery to detect preclinical signs of central nervous system impairment: the battery includes the Santa Ana (Helsinki version) test, simple reaction time, the Benton test, and the Wechsler digit span and digit symbol. In addition, the Gordon test was used to study personality profiles and the clinical depression questionnaire. Urinary mercury was used as indicator for internal dose. To this effect, urinary mercury observed in workers examined from 1979 to 1987 was evaluated. Of the pyschic functions explored by behavioural tests, only short term auditory memory was found to be impaired in the chronically exposed workers (p less than 0.05 compared with the controls). The chronically exposed workers were also found to be more depressed than those in the two other groups. No changes of visual motor functions were observed. The personality of the occupationally exposed workers was found to be considerably changed compared with that of the control group. On the basis of the results obtained and in view of urinary mercury mean concentrations in the exposed group which were 30-40 micrograms/l over the years, it is suggested that the TLV-TWA for mercury should be lowered to 0.025 mg/m3 and that the biological urinary exposure indicator for biological monitoring should be 25 micrograms/l. PMID- 2310715 TI - Nasal mucosa in workers exposed to formaldehyde: a pilot study. AB - This study evaluates the histological changes, especially the presence of possible precancerous lesions, in the nasal mucosa of workers exposed to formaldehyde. Nasal biopsies of 37 workers occupationally exposed to formaldehyde for more than five years and 37 age matched referents showed a higher degree of metaplastic alterations in the former group. In addition, three cases of epithelial dysplasia were observed among the exposed. These results indicate that formaldehyde may be potentially carcinogenic to man. Combination of this finding with the inconclusive epidemiological studies suggests that formaldehyde is a weak carcinogen and that occupational exposure to formaldehyde alone is insufficient to induce nasal cancer. PMID- 2310716 TI - Mortality from circulatory diseases, especially ischaemic heart disease in sea pilots and boatmen in Sweden 1951-84: a retrospective cohort study. AB - A cohort of 1455 sea pilots and boatmen employed after 1921 was established. Those identified and alive in 1951 (n = 1323) were linked to the Swedish cause of death register 1951-84. In 21 352 person-years 383 deaths were observed among sea pilots compared with 379.3 expected (SMR = 101;95% CI between 99 and 112) and in 12,127 person-years the observed number of deaths among boatmen was 136, expected 135.9 (SMR = 100) when Swedish men were used as a reference population. For ischaemic heart disease (IHD) (ICD-8: 410-414) the SMR was equal to 96 (obs = 131, exp = 137.2) for sea pilots and 91 (obs = 44, exp = 48.4) for boatmen. No trend over time or geographical differences could be observed. A healthy worker effect could not explain why there was no excess mortality from IHD. PMID- 2310717 TI - Serum lipoproteins in day and shift workers: a prospective study. AB - This study was designed to assess changes in diet and serum lipoproteins in shift workers. Twelve shift workers and 13 day workers were examined before employment and after six months at work. Total cholesterol and serum triglycerides did not change significantly. In both groups a decrease in systolic blood pressure was observed. The ratio between apoB and apoA-1 lipoproteins increased by 18% in shift workers compared with 5% in day workers. The change in the ratio between apoB and apoA-1 lipoproteins showed a significant inverse correlation with the change in intake of dietary fibres. PMID- 2310718 TI - Cardiac arrhythmias during occupational exposure to fluorinated hydrocarbons. AB - The effects of occupational exposure to chlorodifluoromethane (FC 22) and dichlorodifluoromethane (FC 12) on cardiac rhythm were examined. The subjects were six men who repaired refrigerators (age 31-56, mean 46 years) and a control group of six plumbers (age 29-54, mean 45 years). Ambulatory electrocardiograms (ECG) were recorded for 24 hours on the day of exposure and on a control day. The ECG tapes were automatically analysed with a Reynolds pathfinder 3 apparatus and all aberrant complexes recorded by the machine were checked. One person read all the tapes without knowing whether or not they were recorded during exposure. The number of ventricular ectopic beats were compared between the day of exposure and the control day and with the tape of the control. In addition, the number of ventricular ectopic beats during exposure was compared with the number occurring during the rest of the day. The concentrations of fluorocarbons were measured in four instances. High peak concentrations of fluorocarbons (1300-10,000 cm3/m3) were measured during refrigerator repair work. No clear connection between fluorocarbons and cardiac arrhythmia was found, although one subject had several ventricular ectopic beats which may have been connected with exposure. PMID- 2310719 TI - Smoking and mortality from coalworkers' pneumoconiosis. PMID- 2310720 TI - Longitudinal respiratory survey of shipyard workers: effects of trade and atopic status. AB - A respiratory sample survey of 609 shipyard workers was conducted in 1979: the men were reassessed an average of 7.2 years later. The 53 deaths between the surveys were related to age, level of lung function and smoking but not to trade as a welder or caulker/burner. Of the survivors, 488 (88%) were seen, including 425 men who had retired or been made redundant. Redundancy was related to age, smoking, and respiratory symptoms; the average reduction in duration of employment per symptom was 0.44 years. Changes in respiratory symptoms included onset of chronic bronchitis and wheeze on most days (numbers respectively 77 and 109) and increased breathlessness on exertion (n = 89); significant related factors included smoking, previous metal fume fever or pneumonia, and, for breathlessness, trade as a welder or caulker/burner. Electrocardiographic evidence for myocardial ischaemia was also associated with increased breathlessness. The annual declines in FEV1 and other spirometric indices were related to age, to being a smoker at the time of the initial survey, and to trade as a welder or caulker/burner compared with trades that did not involve welding or burning. There was significant interaction between these effects. In a subsample of 124 redundant workers there was also significant interaction between the effects of fumes and atopy (skin test positive to common antigens) or a raised serum IgE concentration. It was concluded that welding fumes interacted with smoking and an atopic constitution to cause respiratory impairment. The results related mainly to exposures in the past and were not necessarily relevant for present day conditions in the industry. PMID- 2310721 TI - Mortality and cancer incidence in chloralkali workers exposed to inorganic mercury. AB - Mortality and cancer incidence were studied in men exposed to inorganic mercury at eight Swedish chloralkali plants where individual biological monitoring data were available. Urinary mercury excretion has declined from about 200 micrograms/l during the 1950s to less than 50 micrograms/l today. These workers had also been exposed to chlorine and static magnetic fields. At some of the plants there had been a low degree of exposure to asbestos. In total, 1190 men had been monitored for at least one year between 1946 and 1984. Their mortality and cancer incidence were compared with those of the general male population. Mortality from all causes was not significantly increased (rate ratio = 1.1). Cardiovascular mortality was slightly increased (rate ratio = 1.3; 95% CI 1.0 1.5) for no known reason. An excess of lung tumours was seen (rate ratio = 2.0; 95% CI 1.0-3.8), possibly caused by previous exposure to asbestos. Mortality from non-malignant diseases of the brain and the kidneys, the main target organs in mercury poisoning, was not increased, nor was the incidence of brain tumours (3 observed v 1.1 expected) or kidney tumours (3 observed v 1.9 expected). PMID- 2310722 TI - Cyclocryotherapy: a review of cases over a 10-year period. AB - There are conflicting reports on the value of cyclocryotherapy in the management of glaucoma. This retrospective study was carried out to assess the efficacy and complication rate of this procedure. The case notes of all patients undergoing cyclocryotherapy at a single centre over a 10-year period were reviewed. Case records were available for 68 eyes of 64 people. Thirty-eight eyes had neovascular glaucoma, nine had aphakic glaucoma, nine had angle closure glaucoma, three had primary open angle glaucoma, and nine had secondary open angle glaucoma. The mean follow-up periods for these groups varied from 2.0-6.3 years. The mean reduction in intraocular pressure following treatment varied from 7.9 mm Hg in the secondary open angle glaucoma group to 24.3 mm Hg in those with angle closure glaucoma. Pressure was controlled in 29.4% overall, ranging from 66.7% in the angle closure and primary open angle groups to 0% in the secondary open angle group. Of the painful eyes 71% were rendered comfortable, indicating that pain relief from cyclocryotherapy is not due solely to pressure control. 30% of the patients lost their vision following the procedure, phthisis occurred in 11.8% and four eyes (5.9%) went on to enucleation. Our results indicate that cyclocryotherapy affords good pain relief, without good pressure control, in various types of glaucoma. While there is an apparent high complication rate, visual loss and phthisis cannot be ascribed directly to the procedure, since these are eyes with a poor prognosis. PMID- 2310723 TI - Macular recovery function (nyctometry) in diabetics without and with early retinopathy. AB - Nyctometry was used to assess macular recovery function in 234 diabetic patients; their retinopathy ranged from no retinopathy (99) to early background retinopathy (135). None had visual symptoms or macular oedema. Abnormal (reduced) nyctometry findings were significantly and directly related to the deterioration of diabetic retinopathy. There was no significant association between reduced or normal nyctometry findings and glycaemia at the time of the examination. The value of nyctometry in screening and follow-up is discussed. PMID- 2310724 TI - Infective conjunctivitis and corneal scarring in three brothers with sex linked hypogammaglobulinaemia (Bruton's disease). AB - The ocular findings in three brothers with Bruton's disease are reported. All three boys had purulent conjunctivitis, but the two older brothers also developed marked corneal scarring with visual impairment. Haemophilus influenzae was cultured from conjunctival swabs; it was resistant to neomycin but sensitive to chloramphenicol. Tear analysis showed that the three subjects had normal levels of lysozyme but no detectable IgA. PMID- 2310725 TI - Ciliary body melanoma with optic nerve invasion. AB - A case of melanoma of the ciliary body is presented. Initially the patient was diagnosed and treated for uveitis, but following CT scanning and ultrasound a tumour was detected and the eye enucleated. Histopathologically it was found that the tumour had invaded the optic nerve head, apparently via Cloquet's canal. PMID- 2310727 TI - The living contact lens. PMID- 2310726 TI - Chart for visual acuity screening. PMID- 2310728 TI - Paediatric cataract surgery. PMID- 2310729 TI - Epikeratophakia for aphakia, keratoconus, and myopia. AB - A series of 67 cases of epikeratophakia is presented with an average time from surgery of 12.2 months. For aphakia there was a delay in the recovery of vision, but by nine months 83% of 57 patients achieved an acuity equal to, or within 1 line of, the preoperative value. 57% were corrected to within 3 dioptres of emmetropia, but in the latter part of the series 75% were within this range. Astigmatism and reduced contrast sensitivity, especially in the presence of glare, were important complications. For keratoconus, 86% of seven patients with over two months of follow-up achieved a spectacle corrected acuity of 6/9 or better. One patient had surgery for myopia and obtained the desired refractive correction. PMID- 2310730 TI - Lens surgery in infancy and childhood. AB - The medical records of 224 children who had lens surgery performed at the Hospital for Sick Children during the 10-year period 1978-88 were reviewed. There were 12 children with ectopia lentis; these patients achieved a mean postoperative acuity of 0.68 (6/8.8), and no operative or postoperative complications were noted. Two hundred and twelve children had lens surgery for cataracts or for retrolental abnormalities with a clear lens. Children with bilateral congenital cataracts achieved a mean acuity in the better eye of 0.32 (6/18). In a series of carefully controlled unilateral congenital cataracts the visual results were poor. The postoperative complication rate for cataract and clear lens surgery was 4.6%. Because visual results are probably better with early surgery we emphasise that every newborn baby should be tested for media opacities. PMID- 2310731 TI - Factors relating to visual acuity in children who have been treated for convergent squint. AB - Retrospective analysis of a selected sample of children who presented with convergent squint has shown that abnormal meridional hypermetropia (3.5 D or more) at age 1 was the principal factor associated with severe amblyopia (6/24 or less) remaining after conventional treatment. Neither the reported age of onset nor delay in presentation influenced the final visual outcome. PMID- 2310732 TI - A prevalence survey of ophthalmic diseases among the Turkana tribe in north-west Kenya. AB - A prevalence survey of ophthalmic disease was conducted among the Turkana tribe in northwest Kenya. Altogether 900 people were examined in different sites of the semiarid and arid Turkana region. The findings show the prevalence of blindness to be 1.1% and the prevalence of blindness in one eye to be 6.8%. The major causes of blindness up to age 35 were corneal disease from xerophthalmia and trachoma and above age 45 cataract. Trauma was a major cause of monocular blindness. The prevalence of trachoma and its complications was 42.8% and the prevalence of cataract 5.2%. Cataract begins to form at an early age (25-35). The prevalence of xerophthalmia was 44%. These findings are similar to previously reported studies in Africa, especially in semiarid areas. The main remedy lies in improvement of education and the environment. PMID- 2310733 TI - Orbital recurrence of retinoblastoma successfully treated by combined therapy. AB - Five children with an orbital recurrence of retinoblastoma have been successfully treated by a combination of excision biopsy of the tumour mass, radical orbital radiotherapy, and systemic chemotherapy. Nine previous children, consecutive with the five presented here, died from disseminated retinoblastoma after failure of earlier treatment programmes for orbital recurrence. An aggressive therapeutic approach is justified by this improvement in survival. PMID- 2310735 TI - The Barry Project--a three-dimensional assessment of occlusal treatment change in a consecutively referred sample: the incisors. AB - The serial occlusal changes for a consecutively referred sample of malocclusion from a Welsh town are presented. The patients were assigned to one of four treatment regimes (meant to represent those commonly used in the U.K.) and treated to a rigid protocol. Twenty-five per cent of the cases were reviewed by an eight clinician panel. No bias in the original assignments was found although there was considerable interobserver variation. At defined pretreatment, post treatment, and post-retention stages, records were collected and the study casts quantitatively measured using a reflex metrograph and an occlusal analysis programme. The results found for the overjet, overbite, crown inclination, and crown angulation are presented and discussed. PMID- 2310734 TI - Anterior ischaemic optic neuropathy and intraocular pressure. AB - Anterior ischaemic optic neuropathy is a stroke syndrome of the distal optic nerve, characterised by disc oedema and optic nerve dysfunction--loss of central vision, loss of colour vision, a relative afferent pupillary defect, and nerve fibre layer field loss. We prospectively evaluated the changes of intraocular pressure throughout the day in 16 patients with non-arteritic anterior ischaemic optic neuropathy and 15 normal control subjects of similar age and race. The peak intraocular pressure exceeded 21 mm Hg in five of the ischaemic optic neuropathy patients but none of the controls. The mean peak intraocular pressure was 19.9 mm Hg for the ischaemic optic neuropathy group versus 17.6 mm Hg for controls (p = 0.034). The range of intraocular pressure was also greater for the ischaemic optic neuropathy group (p = 0.030). Eight of 16 ischaemic optic neuropathy patients had a range of intraocular pressure of 6 mm Hg or more, compared with three of 15 control subjects. The intraocular pressure exceeded 21 mm Hg during a subsequent visit in two additional patients in whom the hourly determined intraocular pressure peaked at less than 21 mm Hg. Thus, seven of 16 of our ischaemic optic neuropathy group had an intraocular pressure exceeding 21 mm Hg during the study period. Raised intraocular pressure may be a predisposing factor in some patients who develop anterior ischaemic optic neuropathy. PMID- 2310736 TI - Autotransplantation of premolar teeth to replace missing maxillary central incisors. AB - Orthodontic treatment decisions when maxillary central incisors are absent or are of poor prognosis, are discussed. Autotransplantation of mandibular first premolars to the incisor region is suggested as an approach in selected cases. The literature is reviewed, surgical technique described and case selection summarized. Cases are reported where autotransplantation of premolars to the maxillary incisor region has produced good functional and aesthetic results. PMID- 2310737 TI - Post-orthodontic splinting of periodontally-involved teeth. AB - Shortcomings of techniques presently available for the stabilization of periodontally-involved teeth following orthodontic therapy are discussed. The rationale for rigid fixation of such teeth is questioned in the light of modern concepts of tooth mobility. An inexpensive technique of tooth stabilization based on wire and composite resin is described. The technique permits fixation allowing for individual periodontal adjustment, yet with minimal interference with tooth structure and the occlusion. PMID- 2310738 TI - A cephalometric study to compare the effects of cervical traction and Andresen therapy in the treatment of Class II division 1 malocclusion. Part 1--Skeletal changes. AB - Lateral cephalometric radiographs at the beginning of treatment, end of active treatment, and post-treatment of 30 Andresen and 40 cervical traction patients were analysed, and compared with those of a control group of 22 untreated cases. The cervical traction group was divided into a non-extraction group and an extraction of maxillary second molars group. A clinically significant reduction of ANB was achieved, mainly by mandibular changes in the Andresen group and by maxillary changes in the cervical traction groups. Cervical traction was associated with a small distal positioning and anterior downward tipping of the maxilla during treatment. A more favourable sagittal position of the mandible was achieved in the Andresen group compared to the cervical traction groups, particularly the non-extraction group, where a greater transient backward rotation of the mandible occurred during treatment. A significant, but clinically small increase in mandibular body length occurred in Andresen patients compared to the control. However, in both treatment groups this was due to an increase in growth of the vertical ramus. The lower face heights, both anterior and posterior, increased in all groups, with the anterior upper face height also increasing in the cervical traction group. PMID- 2310739 TI - A posterior open bite. AB - A case of bilateral posterior open bite, treated using the 'straight wire' appliance, is reported. The diagnostic problems, associated with this type of malocclusion, are discussed. PMID- 2310740 TI - At last--a disposable articulator! AB - A simple disposable hinge articulator is described and its advantages in orthodontic clinical practice discussed. PMID- 2310741 TI - Torque-in-base: another straight-wire myth? AB - The theoretical inaccuracies of straight-wire systems which incorporate torque in the bracket face are discussed, with the conclusion that this variation from the original design is unlikely to be of any practical significance. PMID- 2310742 TI - Orthodontic continuing education in the UK. PMID- 2310743 TI - Regulation of Ca2+ transport in brain mitochondria. I. The mechanism of spermine enhancement of Ca2+ uptake and retention. AB - Spermine enhances electrogenic Ca2+ uptake and inhibits Na(+)-independent Ca2+ efflux in rat brain mitochondria. As a result, Ca2+ retention by brain mitochondria increases greatly and the external free Ca2+ level at steady-state can be lowered to physiologically relevant concentrations. The stimulation of Ca2+ uptake by spermine is more pronounced at low concentrations of Ca2+, effectively lowering the apparent Km for Ca2+ uptake from 3 microM to 1.5 microM. However, the apparent Vmax is also increased. At low Ca2+ concentrations, Ca2+ uptake is diffusion-limited. Spermine strongly inhibits Ca2+ binding to anionic phospholipids and it is suggested that this increases the rate of surface diffusion which reduces the apparent Km for uptake. The same effect could inhibit the Na(+)-independent efflux if the rate of efflux is limited by Ca2+ dissociation from the efflux carrier. In brain mitochondria (but not in liver) the spermine effect depends on the presence of ADP. In a medium that contains physiological concentrations of Pi, Mg+, K+, ADP and spermine, brain mitochondria sequester Ca2+ down to 0.1 microM and below, depending on the matrix Ca2+ load. Moreover, brain mitochondria under the same conditions buffer the external medium at 0.4 microM, a concentration at which the set point becomes independent of the matrix Ca2+ content. Thus, mitochondria appear to be capable of modulating calcium oscillations in brain cells. PMID- 2310744 TI - Regulation of Ca2+ transport in brain mitochondria. II. The mechanism of the adenine nucleotides enhancement of Ca2+ uptake and retention. AB - ADP greatly enhances the rate of Ca2+ uptake and retention in Ca2+ loaded mitochondria. Atractyloside, a specific inhibitor of the ADP/ATP translocator, completely inhibits the ADP effect, while bongkrekate, another specific inhibitor of the translocator enhances the effect of ADP. These results indicate that locking the ADP/ATP translocator in the M-state is sufficient to produce the ADP effect. Cyclosporin A, a specific inhibitor of the Ca2(+)-induced membrane permeabilization does not substitute for ADP, indicating that ADP directly affect the rate of electrogenic Ca2+ uptake. The effect of the translocator conformation on the rate of electrogenic Ca2+ uptake is independent of the concentration of Pi and is not caused by changes in membrane potential. However, locking the carrier in the M-state appears to increase the negative surface charge on the matrix face of the inner membrane. This may lead to an enhanced rate of Ca2+ dissociation from the electrogenic carrier at the matrix surface. The rate of Na(+) independent Ca2+ efflux is only slightly inhibited by locking the carrier in the M-state, presumably due to the same mechanism. In the presence of ADP, Pi inhibits the Na(+)-independent efflux. In the presence of physiological concentrations of spermine, Pi and Mg2+, the rate of Ca2+ uptake, Ca2+ retention and Ca2+ set points depend sharply on ADP concentration at the physiological range of ADP. Thus, changes of cytosolic ADP concentration may lead to change in the rate of Ca2+ uptake by mitochondria and thus modulate the excitation relaxation cycles of cytoplasmic free calcium. PMID- 2310745 TI - Quantitative analysis of uncoupling activity of substituted phenols with a physicochemical substituent and molecular parameters. AB - The uncoupling potency of a series of substituted phenols with rat-liver mitochondria was analyzed quantitatively with physicochemical substituent and molecular parameters such as log P, P being the partition coefficient in a phosphatidylcholine liposome/water system, log KA, KA being the acid dissociation constant, and the Taft-Kutter-Hansch steric constant, Es, for ortho-substituents. The potency evaluated from the concentration in the medium required for a defined response was analyzed, showing that the incorporation of compounds in terms of log P, a certain balance between neutral and ionized forms expressible by a parabolic function of log KA and the steric shielding effect of the ortho substituents on the negatively charged center of ionized form are highly significant factors governing the variations in potency. The potency was also quantitatively separated into the intrinsic potency as the protonophore inside the inner mitochondrial membrane and the incorporation factor in terms of log P. Some phenols found as outliers from the correlations and some others distorting the quality of the correlations were shown to have inhibitory effects on the respiratory chain by specific and non-specific modes of action, respectively, besides uncoupling activity. PMID- 2310746 TI - One-electron reduction of the oxy form of cobalt-substituted hemoproteins. AB - The reduction of oxy forms in cobalt-substituted hemoproteins by the hydrated electron (e(aq)-) was investigated by pulse radiolysis. The hydrated electron (e(aq)-) reacted with the oxy form of cobalt horseradish peroxidase (CoHRP) to form CoHRP. On the other hand, the initial product observed in the reaction of the oxy form of cobalt myoglobin (CoMb) with e(aq)- is neither CoMb nor Co3+ Mb. Subsequently, the product was found to convert to another form, the irreversible change in the porphyrin. In contrast to e(aq)-, both oxy forms of CoMb and CoHRP were reduced by various electron donors to form the cobaltic forms. PMID- 2310747 TI - Oxidant-induced haemoprotein degradation in rat tissue slices: effect of bromotrichloromethane, antioxidants and chelators. AB - Haemoprotein degradation and lipid peroxidation were evaluated in rat liver, kidney and heart slices incubated for 2 h in the presence and absence of bromotrichloromethane, antioxidants and chelators to obtain information about the relationship between oxidants and damage to haemoproteins. Haemoproteins were modified by bromotrichloromethane, and this modification, measured as loss of ferrohaemoproteins, generally was concurrent with lipid peroxidation measured as thiobarbituric acid-reactive substances. These two processes occurred simultaneously as a function of incubation time and oxidant concentration. Inhibition of the two processes by nordihydroguaiaretic acid, butylated hydroxyanisole and Trolox C, and lack of inhibition by mannitol, catalase and superoxide dismutase also were coincident. However, Methylene blue, EDTA, sodium fluoride, 2,4-dinitrophenol, N-ethylmaleimide and o-phenanthroline affected the two processes differently. The results suggested that haemoproteins may compete with other molecules for oxidant radicals, thus serving as protectors of cells against oxidant radicals. Products of haemoprotein degradation such as protein polymers, free amino acids and bilirubin may be indicators of in vivo oxidative stress. PMID- 2310748 TI - Characterization of ferrochelatase in kidney and erythroleukemia cells. AB - Ferrochelatase from bovine kidney mitochondria has been purified 1600-fold with a 6.5% yield, exhibiting a specific activity of 490 nmol mesoheme formed/mg of protein per min. The Km values for mesoporphyrin IX and protoporphyrin IX with iron were 12.5 and 12.7 microM, respectively. The Km values for iron and zinc with mesoporphyrin IX were 3.51 and 3.17 microM, respectively. The purified enzyme showed a single band with an apparent molecular mass of 42,000 daltons (42 kDa) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The rabbit antibody against the purified enzyme markedly inhibited activities of the enzyme from both the kidney and liver. Immunoblot analysis showed that the antibody reacted with the renal as well as the hepatic enzymes showing the same molecular weight. Peptide mapping with trypsin or alpha-chymotrypsin showed that digested peptides of renal enzyme were similar to those of hepatic enzyme. Ferrochelatase activity in mouse erythroleukemia (MEL) cells increased in parallel with an increase of heme synthesis by treatment with dimethylsulfoxide. Using immunoblotting techniques, the amount of the enzyme in the MEL cells has been shown to increase by the induction, showing a molecular mass of 41 kDa which was the same as that of the mouse hepatic enzyme. Comparative structural analysis of the enzyme of MEL cells and that of mouse liver by peptide mapping showed that the partial digestive peptides of both enzymes exhibited a similar pattern. These results strongly suggest that ferrochelatase in kidney, liver and erythroid cells can be of one type. PMID- 2310749 TI - The unfolding and attempted refolding of citrate synthase from pig heart. AB - The unfolding of the dimeric enzyme citrate synthase from pig heart in solutions of guanidinium chloride (GdnHCl) was studied. Data from fluorescence, circular dichroism (CD) and thiol group reactivity studies indicated that the enzyme was almost completely unfolded at GdnHCl concentrations greater than or equal to 4 M. On dilution of GdnHCl, essentially no reactivation of the enzyme occurred. The implications of this finding for the process of folding and assembly in vivo of this and other mitochondrial enzymes are discussed. Exposure of the enzyme to high pH (9-10) led to only a small loss of secondary structure and partial reactivation could be observed on readjustment of the pH to 8.0. PMID- 2310750 TI - Purification and partial characterization of rat macrophage Fc receptor and binding factor for IgA. AB - By using a biotinylated ligand and Western blotting techniques, a receptor (RFc alpha) and a binding factor (BF) for IgA were detected, respectively, on membrane and in the cell-free culture supernatant of rat peritoneal macrophages. Extraction of the RFc alpha was obtained by solubilization of macrophages with Nonidet P-40, and purification was performed by HPLC affinity chromatography on a column derivatized with IgA. RFc alpha is formed of two subunits, with molecular masses of 56 and 70 kDa, which are both involved in the IgA binding ability of rat peritoneal macrophages. IgABF was recovered from the cell-free supernatant of a short-term culture of rat macrophages and was affinity-purified in the same manner as RFc alpha. Like RFc alpha, IgABF retained its IgA binding activity in its native, as well as denatured form. Since the molecular masses of RFc alpha and IgABF are similar, and IgABF competes with RFc alpha for IgA binding, one can assume that IgABF probably represents a shed RFc alpha. PMID- 2310751 TI - A nuclear magnetic resonance study of axial ligation for the reduced states of chloroperoxidase, cytochrome P-450cam, and porphinatoiron(II) thiolate complexes. AB - The reduced forms of cytochrome P-450cam and chloroperoxidase were examined by proton NMR spectroscopy. The pH and temperature dependences of the proton NMR spectra of both ferrous enzymes are reported. A series of alkyl mercaptide complexes of both synthetic and natural-derivative iron(II) porphyrins was also examined. The proton NMR spectra of these complexes facilitated the assignment of resonances due to the axial ligand in the model compounds on the basis of their isotropic shifts and multiplicities. Comparison of model compound data with that for the reduced enzymes supports assignment of the methylene protons for the axial cysteinate of ferrous cytochrome P-450cam and ferrous chloroperoxidase to proton NMR resonances at 279 and 200 ppm (pH 7.0, 298K), respectively. Differences in the active site structure of the two enzymes are further demonstrated by 15N-NMR spectroscopy of the cyanide complexes of the ferric forms. PMID- 2310752 TI - Purification and characterization of a low and a high molecular weight form of epidermal growth factor from rat urine. AB - Two forms of epidermal growth factor (EGF) have been purified to homogeneity from rat urine by immunoaffinity chromatography and gel filtration. For one of the purified peptides the molecular mass has been determined to be 5891 by mass spectrometry. This peptide consists of 51 amino acid residues. The sequence of the first 48 amino acid residues is identical to the previously published sequence for submandibular rat EGF. The C-terminal three residues (49-51) are Trp Trp-Lys. The other purified peptide has a molecular mass of 45 kDa as determined by SDS-polyacrylamide gel electrophoresis. The N-terminal sequence is Asn-Tyr-Lys Asp-(Cys)-Gly-Pro-Gly-Gly-(Cys)-Gly-Ser-His-Ala. Both the high and the low molecular mass form of urinary rat EGF are able to bind to the human placenta receptor for EGF. PMID- 2310753 TI - Conformational calculations on the Ala14-Pro27 LC1 segment of rabbit skeletal myosin. AB - In order to define the conformational characteristics of a singular Ala14-Pro27 segment in myosin LC1, conformational calculations were performed using the Simplex algorithm of Nelder and Mead (Computer J. 7 (1965) 308-313) in the ACME program proposed by Tournarie (J. Appl. Cryst. 6 (1973) 309-346). The (Ala-Pro) n = 1 unit was assigned a given conformation x; the conformation energy was then minimized for n = 1 to n = 7 by adjusting structural parameters (angle values). Similarly, 13 different possible conformations were optimized and compared, showing that a (beta 2R)7 conformation is favored by about 20 kcal per mol over the next most probable conformation (C7R)7. In the beta 2R conformation, the (Ala Pro)7 segment is a wide helix, 15 A in length and 8.65 A in diameter, while the C7R conformation results in a semi-extended structure of 25 A long, with an approximate diameter of 6 A. These characteristics are in agreement with available experimental data and putative functions of the LC1 N-terminus. PMID- 2310754 TI - The complete sequence of the acidic subunit from Mojave toxin determined by Edman degradation and mass spectrometry. AB - Mojave toxin, a heterodimeric, neurotoxic phospholipase complex from Crotalus scutulatus scutulatus, is one of a group of closely related rattlesnake toxins for which much structural information is still lacking. The complete amino-acid sequence of the acidic subunit from Mojave toxin was determined. The three individual peptide chains, derived from the acidic subunit by reductive alkylation, were separated by high-performance liquid chromatography. Fragmentations of the A and B chains were done using specific proteinases and the resulting peptide mixtures were fractionated by reverse-phase high-performance liquid chromatography. Sequence analyses on the intact chains and the fragments from digests were done by automated Edman degradation, carboxypeptidase Y degradation and triple-quadrupole and tandem-quadrupole Fourier-transform mass spectrometry. The sequence for each acidic subunit chain is very similar to the corresponding chain from the related neurotoxin complex, crotoxin, and overall the sequence is similar to the sequences of group I and II phospholipases A2. The N-terminus of the B chain is blocked by pyroglutamic acid. The existence of two distinct and closely related C chains was established. It is unlikely that the small sequence difference can account for the isoforms that are present in purified Mojave toxin and in unfractionated venom. PMID- 2310755 TI - Effect of streptozotocin-induced diabetes on sex differences in biliary lipid secretion in the rat. AB - Diabetes mellitus is often associated with lipid abnormalities that may differ with sex. In this work we studied biliary lipid secretion in male and female anaesthetized Wistar rats (250 g). Diabetes was induced by a single intraperitoneal injection of streptozotocin (6 mg/100 body weight) 6 days before carrying out the studies on bile secretion. Our results confirm the existence of sex differences in bile formation and composition, most of them probably due to a higher (+27%) bile acid output in the female animals. Diabetes induced profound alterations in these sex differences. (a) Bile flow was reduced in both sexes, but more markedly so in female diabetic rats; thus the difference observed in healthy animals was reduced (from 2.22 to 1.58 and from 1.84 to 1.40 microliters/min per g liver in female and male rats, respectively). (b) Bile acid and phosphatidylcholine outputs were increased to a similar extent (bile acid output: from 46.7 to 55.8 nmol/min per g liver, in females and from 36.8 to 50.7 nmol/min per g liver, in males; phosphatidylcholine output: from 3.3 to 13.1 nmol/min per g liver, in females and from 4.5 to 12.5 nmol/min per g liver, in males), and hence the sex differences were abolished. (c) Cholesterol output was increased in both sexes, but this enhancement was significantly higher in female rats (from 0.75 to 1.31 and from 0.65 to 0.89 nmol/min per g liver, in females and males, respectively). (d) The fractional pool of phospholipid species secreted into bile was different in female compared with male rats. The percentage of phosphatidylcholine was higher in female than in male healthy rats. Streptozotocin treatment reversed this proportion, which suggests that changes in the phospholipid composition of the canalicular plasma membrane may play a role in the observed alterations in biliary lipid secretion during diabetes mellitus. Most of the above-described streptozotocin-induced changes were prevented by insulin replacement from the 3rd to the 6th days after streptozotocin injection. In summary, the present study describes alterations in sex differences in biliary lipid secretion of streptozotocin-induced diabetes. These changes are dependent on the insulin deficiency state rather than on a direct hepatotoxicity of the diabetogenic drug. PMID- 2310756 TI - Glycerophospholipids and cholesterol composition of bile in bile-fistula rats treated with monensin. AB - Data regarding the action of monensin on the concentrations of glycerophospholipids and cholesterol in bile of rats subjected to total biliary diversion for 3 h are reported. After monensin their concentration in bile drops significantly in the first 60 min collections with respect to the control. Differences seem to be produced between the rates of transport to the bile of glycerophospholipids and cholesterol, not sufficiently explained by the inhibition of bile salt uptake determined by monensin at the sinusoidal pole of the hepatocyte. PMID- 2310757 TI - Rat apolipoprotein B differs in solubility properties from human apolipoprotein B. AB - Apolipoprotein B (ApoB) in general is known as an insoluble protein in aqueous buffers without the initial aid of denaturing agents. However, following the total delipidization of rat plasma low-density lipoproteins, a considerable portion (28.2 +/- 3.0%) of rat ApoB was found directly soluble in an aqueous buffer, N-ethylmorpholine acetate (pH 7.3) as demonstrated by SDS-polyacrylamide gel electrophoresis, immunoblotting and electron microscopic analysis. On the other hand, this was not observed for human ApoB. This solubility difference may suggest some structural differences that exist between rat ApoB and human ApoB. PMID- 2310758 TI - Immunochemical detection of 'platelet type' phospholipase A2 in the rat. AB - Polyclonal antibodies were raised against rat platelet phospholipase A2. One of them, designated as R377 was prepared by immunizing a rabbit with the intact enzyme. The other antibody, designated as R385, was prepared by immunizing with the enzyme treated with 2-mercaptoethanol. The antibody R377 bound to rat platelet phospholipase A2 almost exclusively, while the antibody R385 reacted not only with rat platelet phospholipase A2 but with the enzymes obtained from snake venom or mammalian pancreas. The antibody R377 bound to the non-reduced rat platelet phospholipase A2 bearing intact intramolecular disulfide bonds, but not to the reduced enzyme. In contrast, the antibody R385 reacted with both non reduced and reduced enzymes. R377 may recognize the conformational structure of the enzyme. Both antibodies inhibited the enzyme activity. The antibody R377, but not R385, interfered with the interaction of the enzyme with heparin, which is one of the characteristic properties of rat platelet phospholipase A2. The antibody R377 reacted with phospholipases A2 of bone-marrow cells and of peritoneal exudated cells prepared from caseinate-treated rats, indicating that some myeloid cells other than platelets also contain 'platelet type' phospholipase A2. An immunochemical method for measurement of rat 'platelet type' phospholipase A2 was developed. The sensitivity of this method was 10 ng/ml of phospholipase A2 in the preparation. One of the advantages of the present immunochemical method is that the measurement was not affected by the presence of an endogenous inhibitor(s) of enzymatic activity. PMID- 2310760 TI - Competitive inhibition of lipolytic enzymes. I. A kinetic model applicable to water-insoluble competitive inhibitors. AB - It is now becoming clear from the abundant lipolytic enzyme literature that any meaningful interpretation of inhibition data has to take into account the kinetics of enzyme action at the lipid/water interface. We attempt in the present paper to provide a kinetic model applicable to water-insoluble competitive inhibitors, in order to quantitatively compare the results obtained at several laboratories. We derived kinetic equations applicable to the pre-steady state as well as steady state. By measuring the inhibitory power, as described in the present paper, it is possible to obtain a normalized estimation of the relative efficiency of various potential inhibitors. Furthermore, with the kinetic treatment developed here, it is possible to make quantitative comparisons with the same inhibitor placed under various physico-chemical situations, i.e., micellar or monolayer states. PMID- 2310759 TI - Effects of dietary fats on the fluidity of human high-density lipoprotein: influence of the overall composition and phospholipid fatty acids. AB - The present study was undertaken to analyze whether the changes induced by dietary manipulations in the chemical composition of HDL, particularly in total phospholipids, phosphatidylcholine and sphingomyelin fatty acid composition, modified their fluidity. 12 healthy women, aged 26-49 years were studied. They consumed, over periods of 5 weeks, various isocaloric diets, each containing 30% of the calories as fat. 15.6% of the total calories were provided successively by olive oil, soybean oil, corn oil, and milk fats. The HDL fluorescence anisotropy was measured with 1,6-diphenyl-1,3,5-hexatriene (DPH) by fluorescence polarization. The HDL from the monounsaturated diet, olive oil, were the most fluid particles. The HDL fluorescence anisotropy was positively correlated with their free cholesterol percentage and negatively correlated with their triacylglycerol content and their triacylglycerol/phospholipid ratio. Moreover, the HDL fluorescence anisotropy was negatively correlated with the percentage of oleic acid in their total phospholipids and particularly in the phosphatidylcholine. These results suggest that the percentages of triacylglycerol and oleic acid in phospholipids of HDL have a fluidifying effect on these lipoproteins. PMID- 2310761 TI - Competitive inhibition of lipolytic enzymes. II. Preparation of 'monoacylamino' phospholipids. AB - This paper describes the synthesis of a number of phosphatidylcholines and phosphatidylglycols, in which one fatty acyl ester group is replaced by an acylamino function. The phospholipids, both of the alpha- and beta-type, are prepared in racemic and enantiomeric pure forms. PMID- 2310762 TI - Effect of starvation on lipoprotein lipase activity in the liver of developing rats. AB - Liver lipoprotein lipase activity in neonatal (1- and 5-day-old) rats was 2-3 times than in the liver of adult rats. In mid-suckling (15-day-old) or weaned (30 day-old) animals, it was not significantly different from the low activity detected in adult rats. Starvation resulted in a 3-fold increase of lipoprotein lipase activity in the neonatal liver, but did not affect the activity in the liver of mid-suckling, weaned or adult rats. When isolated livers from both 1- and 5-day-old pups were perfused with heparin, a sharp peak of lipoprotein lipase activity appeared in the perfusate. In fed neonates, the peak area accounted for about 70% of the total (released + non-releasable) activity. In starved neonates, the proportion of heparin-releasable activity increased up to about 90%. These results indicate that neonatal rat liver lipoprotein lipase activity is markedly affected by changes in the nutritional status of the animal, and the effect is restricted to the vascular pool of the enzyme, as was reported in extrahepatic tissues from adult rats. PMID- 2310763 TI - Competitive inhibition of lipolytic enzymes. III. Some acylamino analogues of phospholipids are potent competitive inhibitors of porcine pancreatic phospholipase A2. AB - Competitive inhibition of porcine pancreatic phospholipase A2 was studied in mixed-micellar systems composed of long- and medium-chain substrates, potential inhibitors and detergents. A number of positional and stereoisomeric monoacylamino, acyloxyglycerophospholipids were investigated for their inhibitory properties, using as substrates the corresponding diacyl-sn-glycero-3 phospholipids possessing the same polar headgroup and identical acyl chain lengths. Based on a kinetic model applicable to water-insoluble inhibitors (see accompanying paper I), which allows a quantitative comparison of the inhibitory power (Z) of the various phospholipid analogues, the following results were obtained: Substitution of a single acylester bond in a diacylglycerophospholipid by an acylamino group can transform the substrate molecule in a potent competitive inhibitor. This property is acquired only when this substitution occurs on the phospholipase-susceptible ester bond of the substrate. If the acylamino group replaces an ester bond which cannot be attacked by the highly positional and stereospecific phospholipase, the resulting molecule binds with similar affinity to the active site of the enzyme as the parent substrate molecule. Because of its positional and stereospecificity, this so-called inhibitory 'amide effect' suggests that these inhibitors behave as substrate derived analogues. The inhibitory 'amide-effect' observed with several medium- and long-chain monoacyloxy-, monoacylamino-deoxyglycerophosphatides is completely lost upon specific alkaline hydrolysis of the single acylester bond. Reesterification of the free glycerol OH group in these lysoacylaminophosphoglycerides, even with an acetyl residue, restores the inhibitory properties. These observations indicate that specific binding of phospholipids to the active site of pancreatic phospholipase A2, requires the presence of two chains in substrate or inhibitor structure and suggest that those results obtained with lysophospholipids and single-chain analogues may be questionable. PMID- 2310765 TI - Loading of quin2 into the oat protoplast and measurement of cytosolic calcium ion concentration changes by phytochrome action. AB - The loading of quin2 into oat protoplasts was carried out in an incubation medium (0.6 M sorbitol, 1 mM CaCl2, 5 mM Mes, 5 mM Tris, 0.05% BSA, 1 mM KCl, 1 mM MgSO4 (pH 6.8)), in which we found the best viability of the protoplast and the highest membrane permeability of quin2/AM, compared with the results obtained from any other incubation medium we had tried to use. 50 microns of quin2/AM was added in the suspension medium containing 5 x 10(5)/ml of oat protoplasts, and incubation at 4 degrees C was performed for 24 h. From atomic absorption data, we confirmed that quin2 loading was 1.78 mmol per liter of cells. Red-light (660 nm) irradiation for 5 min caused an increase of the cytosolic Ca2+ concentration from 30 to 193 nM. On the other hand, a subsequent irradiation with far-red light (730 nm) for 5 min decreased it by about 48 nM. Even when the extracellular Ca2+ was completely chelated with 1 mM EDTA, red light increased the cytosolic Ca2+ concentration by about 51 nM and far-red light decreased it to 3 nM. These results imply that the Pfr form of phytochrome functions not only in the process of influx of Ca2+, but also in the mobilization process of Ca2+ from the intracellular Ca2+ pools. The fact that the Pr form of phytochrome lowers the cytosolic Ca2+ concentration is also presented in this report. PMID- 2310764 TI - Characterization of fatty acid elongation system in porcine neutrophil microsomes. AB - Microsomes purified from porcine neutrophils containing the fatty acid chain elongation system for long- and very-long-chain fatty acyl-CoAs, and several enzymatic characters for the elongation of palmitoyl-CoA (16:0-CoA) and arachidoyl-CoA (20:0-CoA) were examined. The heat-inactivation profile for the elongation of 16:0-CoA was different from that of 20:0-CoA, suggesting the presence of different enzyme systems for palmitoyl-CoA and arachidoyl-CoA. Contrary to the elongation system of brain microsomes, the successive synthesis of lignoceric acid (24:0) from 20:0-CoA at 60 microM was not prominent under normal conditions in the neutrophil microsomes. The synthesis of behenic acid (22:0) was slightly inhibited by 0.5 mM N-ethylmaleimide (NEM) present in the assay mixture, whereas the pre-treatment of microsomes with 0.5 mM NEM largely inhibited the synthesis of 22:0 from 20:0-CoA. The synthesis of 24:0, however, was enhanced by 0.5 mM NEM in the elongation of 20:0-CoA and the rate of 24:0 synthesis became dominant over the synthesis of 22:0. These results suggested that the elongation enzyme for very-long-chain fatty acyl-CoA, especially for 20:0-CoA elongation to 22:0 in the neutrophil microsomes contained NEM-sensitive sulfhydryl groups in the active center and the mechanism for the synthesis of 24:0 through successive elongation from 20:0-CoA was different from that of 22:0, as the former was enhanced by NEM whereas the latter was strongly inhibited. PMID- 2310766 TI - Proteolytic processing of chromogranin A in cultured chromaffin cells. AB - The prohormone chromogranin A is the major soluble component of secretory granules in chromaffin cells of adrenal medulla and in many other different endocrine cell types. The proteolytic processing of chromogranin A was studied in cultured bovine chromaffin cells using [35S]methionine to label proteins and a specific antibody to immunoprecipitate the native protein and its breakdown products. In resting cells, it was found that the degradation of chromogranin A is a slow process, since no degradation was observed after a 40 h incubation with radiolabelled methionine. Stimulation of cells with a single pulse or with successive pulses of nicotine did not significantly enhance the degree of proteolytic processing of chromogranin A. As it has recently been shown (Simon, J.P., Bader, M.F. and Aunis, D. Biochem. J. (1989) 260, 915-922) that protein kinase C may be involved in the regulation of chromogranin A synthesis, the possibility that prohormone processing may also be controlled by protein kinase C was examined using the activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA). However, incubation of cells with TPA did not significantly modify chromogranin A processing, indicating that biosynthesis and proteolytic processing of chromogranin A are two distinctly regulated mechanisms. Glucocorticoids are known to exert regulatory control of chromaffin cell metabolism; however, incubation of cells with dexamethasone did not alter slow chromogranin A processing. Stimulation of labelled cells rapidly released newly synthesized chromogranin A into external medium. In addition, released chromogranin A was found to be actively processed into its 60 kDa and 43 kDa breakdown products. This extracellular proteolytic degradation mechanism may be of importance with regard to the function of chromogranin A as a prohormone. PMID- 2310767 TI - 31P-NMR studies of glucose and glutamine metabolism in cultured mammalian cells. AB - 31P-NMR measurements of the concentrations of phosphorus-containing metabolites in mammalian cells immobilised and perifused with glucose and glutamine as sole carbon source have shown that the intracellular Pi concentration is significantly higher in cells perifused with glutamine than with glucose. The data are consistent with the proposal that the rate of glutamine utilisation may be controlled by the activity of phosphate-activated glutaminase. PMID- 2310768 TI - Cellular cholesterol metabolism in mitogen-stimulated lymphocytes--requirement for de novo synthesis. AB - The relationship between cholesterol synthesis and uptake in proliferating lymphocytes has been examined. [14C]Acetate incorporation into lymphocytes cultured under lipoprotein-deficient conditions increased initially in response to mitogen, decreased after 24 h, and increased rapidly between 72 and 96 h. Addition of LDL (10 micrograms/ml) to the culture during the 'trough' period caused [14C]acetate incorporation to return rapidly to baseline, while at peak periods LDL suppression of cholesterol synthesis was minimal. Lymphocytes cultured in the presence of the HMG-CoA reductase inhibitor, mevinolin, exhibited a time-dependent increase in their capacity to incorporate [14C]acetate into cholesterol, evident when mevinolin was removed by washing prior to assay. PHA enhanced 125I-labelled LDL receptor-mediated binding by lymphocytes cultured in lipoprotein-deficient medium over a 4 day period and mevinolin augmented the effect. [3H]Thymidine incorporation into mitogen-stimulated lipoprotein-deficient cultures was inhibited up to 75% by mevinolin (1 mumol/l). LDL (2.5-10 micrograms/ml) substantially reversed this inhibition in 72 h cultures, but only partially overcame inhibition in cells cultured for 96 h. Results suggest that endogenous cholesterol synthesis may be obligatory for lymphocyte proliferation after the initial round of cell division. PMID- 2310769 TI - Role of phosphocreatine in energy transport in skeletal muscle of bullfrog studied by 31P-NMR. AB - To evaluate the energy-shuttle hypothesis of the phosphocreatine/creatine kinase system, diffusion rates for ATP, phosphocreatine and flux through the creatine kinase reaction were determined by 31P-NMR in resting bullfrog biceps muscle. The diffusion coefficient of phosphocreatine measured by 31P-pulsed gradient NMR was 1.4-times larger than ATP in the muscle, indicating the advantage of phosphocreatine molecules for the intracellular energy transport. The flux of the creatine kinase reaction measured by 31P-saturation transfer NMR was 3.6 mmol/kg wet wt. per s in the resting muscle. The flux is equal to the turnover rate of ATP, ADP, phosphocreatine and creatine molecules, therefore, the life-times of these substrates and the average distance traversed after the life-times by the diffusing molecules were calculated using the diffusion coefficients obtained by 31P-NMR. The mean square length of one-dimensional diffusion was 22 microns in ATP molecules and the minimum diffusion length was 1.8 microns in ADP molecules. The latter was calculated using free ADP concentration, 30 mumol/kg wet wt., obtained from the equilibrium constant of the creatine kinase reaction and the diffusion coefficient assumed to be the same of ATP in muscle. Similar diffusion lengths of ADP were calculated using the reported values for the flux of the creatine kinase reaction in heart and smooth-muscle. The diffusion lengths of all substrates involved in the creatine kinase reaction were larger than the radii of myofibrils. Therefore, in the muscles with an alternating arrangement of mitochondria and myofibrils, such as heart and certain skeletal muscles, ATP and ADP molecules can move freely between myofibrils and mitochondria without the aid of the creatine kinase reaction; thus, we conclude that the energy-shuttle hypothesis is not obligatory for energy transport between the mitochondria and the myofibrils. PMID- 2310770 TI - Analysis of free inositol trisphosphate in heart tissue by FPLC and isotachophoresis. AB - Recent, increasing interest in inositol tris(1,4,5)phosphate (IP3) turnover and metabolism has led to a need for a fast and quantitative determination of this compound in various tissues. These requirements are fulfilled by separation in different steps (FPLC and Sephadex G-10) culminating in further separation and quantification by isotachophoresis. Isotachophoresis means a migration of ion species of the same sign in an electrical field with all ions moving with the same velocity. The migration takes place when an electrical field is applied to a system of electrolytes of specific design. Detection was carried out by monitoring conductivity changes. The method is highly sensitive and allows measurements of IP3 in the pmolar range. Linearity was demonstrated over a wide range, 50-4500 pmol. The total imprecision was low with a coefficient of variation of 3%. When determining in biological tissue the recovery was estimated to be close to 100%. The mean content of IP3 in 15 rat heart specimens was 44.3 pmol/mg dry weight corresponding to tissue samples in the order of 4 mg wet weight. By noradrenaline stimulation myocardial content of IP3 increased by 50%. PMID- 2310771 TI - A novel action of glucocorticosteroid in inhibition of leukotriene C4 production by rat basophilic leukemia cells: suppression of the elevation of cytosolic free Ca2+ induced by antigen. AB - Rat basophilic leukemia (RBL-2H3) cells serve as a model to examine the role of elevated internal Ca2+ concentration ([Ca2+]i), following antigen (DNP10BSA) induced stimulation of leukotriene C4 (LTC4) formation. A novel action of hydrocortisone (HC), to reduce increased [Ca2+]i and consequently inhibit LTC4 formation is assessed. Half-maximal time for elevation of [Ca2+]i induced by antigen was less than 1 min, and maximal elevation of [Ca2+]i (3-fold increase) was reached within 2-3 min. This high [Ca2+]i level waned gradually by 27% during 20 min of incubation. For induction of LTC4 formation, however, there was a refractory period of about 2 min, and half-maximal elevation was at 11 min. Following pretreatment with HC, the antigen-stimulated increase in [Ca2+]i was stunted by 41% at 2-3 min and by 73% at 20 min. LTC4 formation was almost abolished. There was a lag period of at least 2 h to observe any inhibition in both parameters, and the maximal inhibition was about 4 h. Cycloheximide, and receptor antagonist to glucocorticosteroid (RU486) completely prevented the inhibitory effects of HC on elevated [Ca2+]i and LTC4 formation. Estradiol and aldosterone (each at 2.10(-6) M) were virtually inactive, while another glucocorticosteroid, dexamethasone (2.10(-7) M) markedly suppressed antigen induction in both parameters. It is proposed that the inhibitory effect of HC on the formation of LTC4 could be attributed mainly to its ability to reduce elevated [Ca2+]i. PMID- 2310772 TI - Ca2(+)-fatty acid interaction in the control of hepatic gluconeogenesis. AB - Calcium depletion induced by perfusing livers with calcium-free buffer did not alter the rates of basal glucose production from pyruvate or from increasing concentrations of lactate. However, calcium deficiency selectively prevented the fatty acid-induced stimulation of gluconeogenesis from lactate. This effect is not related to the higher NAD redox potential consistently observed in Ca2(+) deficient livers. On the other hand, octanoate was capable of inducing dose dependent changes in the [pyruvate]0.5 in calcium-depleted livers perfused with lactate, ruling out that low cellular calcium content could perturb the mitochondrial transport of pyruvate. The observation that the effect of calcium deficiency can be overcome by supraphysiological concentrations of pyruvate supports the proposal that stimulation of the maximal capacity of the gluconeogenic pathway by fatty acid relies largely on the tricarboxylic acid cycle activity, restricted in calcium deficiency conditions. PMID- 2310773 TI - 2-Deoxy-D-glucose uptake in cultured human muscle cells. AB - Hexose uptake was studied with cultured human muscle cells using 2-deoxy-D-[1 3H]glucose. At a concentration of 0.25 and 4 mM, phosphorylation rather than transport was the rate-limiting step in the uptake of 2-deoxy-D-glucose. This was not due to inhibition of the hexokinase activity by either ATP depletion or 2 deoxyglucose 6-phosphate accumulation. In cellular homogenates, hexokinase showed a lower Km value for glucose as compared to 2-deoxyglucose. Intact cells preferentially phosphorylated glucose instead of 2-deoxyglucose. Therefore, transport instead of phosphorylation may be rate limiting in the uptake of glucose by cultured human muscle cells. These data suggest caution in using 2 deoxyglucose for measuring glucose transport. PMID- 2310774 TI - Suppression of transferrin internalization in myogenic L6 cells by dibucaine. AB - Dibucaine, a potent local anesthetic, is known to suppress myogenesis. The promotion of myogenesis requires transferrin (Tf) which transports Fe to the cells. Therefore, the effects of dibucaine on Fe uptake and Tf internalization were studied using myogenic cell line L6. Dibucaine at 200 microM suppressed 55Fe accumulation which was transported by 55Fe-transferrin to the cells. The anesthetic changed neither the number of Tf receptors nor the affinity of Tf to Tf receptors on the cell membrane. Dibucaine retarded the endocytosis and exocytosis cycle of Tf, and this retardation acted to suppress Fe accumulation. PMID- 2310775 TI - The relationship between mitogen-induced changes in the cytoplasmic pH and free Ca2+ concentration in rat thymocytes. AB - The relationship between pHi and [Ca]i signals generated in rat thymocytes by the mitogen Con A has been investigated. It is shown that the mitogen-induced [Ca]i rise is dependent on Na+/H+ exchange or some other Na(+)-sensitive process. This conclusion is based on the following findings: (i) [Ca]i response to Con A weakens upon decreasing the concentration of extracellular Na+, or inhibiting Na+/H+ exchange; (ii) agents that alkalinize the cytoplasm (the phorbol ester TPA, the Na+/H+ ionophore monensin and NH4Cl) cause an increase in [Ca]i (Klip, A., Rothstein, A. and Mack, E. (1984) Biochem. Biophys. Res. Commun. 124, 14-22; Grinstein, S. and Goetz, J.D. (1985) Biochim. Biophys. Acta 819, 267-270); (iii) The effects of Con A, TPA and monensin on [Ca]i are not additive. The last observation suggests that all these agents activate the same Na+/H+ (Na+ and/or H+)-dependent system of Ca2+ transport. It is found that the pH i and [Ca]i responses in rat thymocytes are sensitive to changes in the intracellular levels of cyclic nucleotides, ATP and in temperature. These regulatory effects on the ionic signals are different for Con A, TPA and monensin. In particular, both the stimulation of Na+/H+ antiport and the [Ca]i rise brought about by Con A or TPA are inhibited upon elevating the cellular cAMP. In contrast, the monensin-induced [Ca]i signal is almost independent of cAMP but is highly sensitive to changes in cGMP and temperature. Reducing the ATP level eliminates both the pHi and [Ca]i responses to Con A but not to monensin. These different characteristics of [Ca]i signals elicited by the mitogen and the Na+/H+ ionophore indicate that these agents use different mechanisms to activate the Na+/H(+)-dependent Ca2+ transporting system. A [Ca]i response to monensin has been obtained in some other cell types, namely, in lymphoblastoid Raji cells, Ehrlich ascites tumor cells and also in platelets. PMID- 2310776 TI - Retinoid modulation of cell-free membrane transfer between endoplasmic reticulum and Golgi apparatus. AB - Cell-free transfer of radiolabeled membrane proteins from part-rough, part-smooth transitional elements of the endoplasmic reticulum to Golgi apparatus immobilized to nitrocellulose in the presence of nucleoside triphosphate, an ATP-regenerating system and a cytosol fraction was promoted by retinol. At an optimum concentration of 1 microgram/ml, the rate and amount of transfer was approximately doubled over 1 to 2 h of incubation in the cell-free system. The transition vesicles induced to form in the cell-free system were concentrated by preparative free-flow electrophoresis in order to study separately the steps of vesicle formation from transitional endoplasmic reticulum and the steps of vesicle fusion with Golgi apparatus. The retinol effect was on vesicle formation as evidenced by an approx. 2-fold increase in transition vesicle numbers, as determined by electron microscope morphometry, and amount from protein determinations on the isolated fractions enriched in transition vesicles. The retinol response in the complete transfer could be eliminated by addition of concentrated cytosol, including cytosol depleted of retinol. An interaction of retinol with some component of the vesicle formation process, possibly involving guanine nucleotides, is indicated. PMID- 2310777 TI - Purification and biological properties of an epithelial intestinal cell growth inhibitor from a human small intestine. AB - Endogenous mitotic inhibitors act as control-mechanisms in intestinal epithelium proliferation. The presence of an inhibitor of cultured intestinal epithelial cell from a villous extract of rat jejunum has been reported in one of our papers. The object of the study now reported was to find the presence of a growth inhibitor in the villous extract from man's small intestine and to purify and characterize this factor when found. Our results reveal that: (1) Such an inhibitor was found in a supernatant preparation obtained from human intestinal epithelial cells. The inhibition of the proliferation of epithelial cells (IRD 98) it induced was seem to be dose-dependent and non-cytotoxic. (2) After chromatography on hydroxylapatite, on DEAE and then on ACA 54 (gel permeation), a low-molecular-weight protein (15 kDa) called purified intestinal inhibitor (PII) was isolated (purification factor of approx. 50,000 with respect to the supernatant fraction). This fraction proved to inhibit the IRD-98 cells in a reversible manner. When cells are incubated with this protein, cells prove to be arrested in phase G1 of the cell cycle as is revealed by the flow cytometry studies. The results obtained support the hypothesis that regulation of cell proliferation is mediated by endogenous inhibitors at the epithelial level. PMID- 2310778 TI - Hibernation activates glyoxylate cycle and gluconeogenesis in black bear brown adipose tissue. AB - Biochemical studies on brown adipose tissue removed from a hibernating black bear and a non-hibernating control animal demonstrate that this tissue: (1) can carry out cyanide-insensitive fatty acid oxidation, and (2) possesses catalase activity and the enzyme activities unique to the glyoxylate cycle, isocitrate lyase and malate synthase. These activities are all markedly increased in brown fat obtained from the hibernating animal. Additionally, hibernation enhances the ability of the tissue to synthesize glycogen in the presence of a fatty acid substrate. The glyoxylate cycle enzymes and the ability to convert fatty acid carbons to glucose have been generally regarded as being absent from vertebrate cells and tissues. PMID- 2310779 TI - Early membrane potential and cytoplasmic calcium changes during mitogenic stimulation of WEHI 231 cell line by polyene antibiotics, lipopolysaccharide and anti-immunoglobulin. AB - Changes in free cytosolic calcium concentration and in membrane voltage are thought to be important initiating events in lymphocyte activation. The antifungal agent amphotericin B (AmB) holds interesting immunomodulating properties and its N-thiopropionyl derivative (AmBSH) is a potent polyclonal B cell activator. These molecules may then exert their stimulating activity through the production of early ionic signals similar to those delivered by the classical activators lipopolysaccharide (LPS) and anti-immunoglobulin (anti-Ig). We addressed this question in a B-cell line (WEHI 231) which has previously been shown to exhibit characteristic response to LPS and anti-Ig. AmBSH protected these cells against anti-Ig-induced cell growth inhibition, providing a LPS-like response. In contrast, the parental compound AmB did not. The two polyene antibiotics did not modify the resting Ca2+i level of the cells, neither did LPS, whereas anti-Ig induced a rapid increase in the cytosolic calcium concentration. On the other hand, polyene antibiotics and LPS promoted membrane depolarization, whereas membrane voltage remained unchanged after anti-Ig treatment. Polyene antibiotics-induced depolarization originated from the increase of membrane permeability to Na+ ions and occurred independently of Ca2+i changes. The relationship between membrane potential and Ca2+i changes in lymphocyte activation are discussed on the basis of these results. Our conclusion was that constitutive Ca2+(-)dependent K+ channels are absent in the WEHI 231 cell line. PMID- 2310780 TI - A sex difference in the effect of prostaglandins on hormone-stimulated glycogenolysis in primary cultures of rat hepatocytes. AB - E series prostaglandins and their biologically active analogue, 16,16 dimethylprostaglandin E2 (dimethylprostaglandin E2), have inhibited hormone stimulated glycogenolysis in hepatocytes cultured from male rats (Okumura, T., Sago, T. and Saito, K. (1988) Biochim. Biophys. Acta 958, 179-187). However, in the case of female rat hepatocytes, it is evident that dimethylprostaglandin E2 did not inhibit the glycogenolysis stimulated by glucagon, isoproterenol (beta adrenergic response) or epinephrine (with propranolol, alpha 1-adrenergic response) in cultures on day 1. Dimethylprostaglandin E2 inhibited such hormone stimulated glycogenolysis in cultures on day 2 and 3, but to a lesser extent than in the male-derived cells. The concentration for 50% inhibition was approx. 10( 8) M; inhibition was completely blocked by a pertussis toxin. Prostaglandin E2 had the same effect as dimethylprostaglandin E2; prostaglandins D2 and F2 alpha had no effect. Additions of sex hormones, 17 beta-estradiol and testosterone, and palmitic acid (diminishing the prostaglandin catabolism) to the culture medium did not change the effect of dimethylprostaglandin E2. These data indicate that a sex difference exists in the inhibition of hepatic glycogenolysis by prostaglandin E2 and its analogue in rat cultured hepatocytes, although the factor causing such a difference is a present unknown. PMID- 2310781 TI - Stimulation of human chondrocyte prostaglandin E2 production by recombinant human interleukin-1 and tumour necrosis factor. AB - In this study we have examined the effects of recombinant cytokine preparations on the production of prostaglandin E2 (PGE2) by human articular chondrocytes in both chondrocyte monolayer and cartilage organ cultures. The cytokines chosen for this study included only those reported to be present in rheumatoid synovial fluids and which therefore could conceivably play a role in chondrocyte activation in inflammatory arthritis. Of the cytokines tested, interleukin-1 (IL 1; alpha and beta forms) consistently induced the highest levels of PGE2 production followed, to a lesser extent, by tumour necrosis factor (TNF; alpha and beta forms). The IL-1s were effective at concentrations 2-3 orders of magnitude less than the TNFs, with each cytokine demonstrating a dose-dependent increase in PGE2 synthesis for the two culture procedures. The increased PGE2 production by the chondrocytes exhibited a lag phase of 4-8 h following the addition of the IL-1 or TNF and was inhibited by actinomycin D and cycloheximide, indicating a requirement for de novo RNA and protein synthesis, respectively. Our results suggest that IL-1 may be the key cytokine involved in modulating chondrocyte PGE2 production in inflammatory arthritis; they further extend the list of human chondrocyte responses which are affected by both IL-1 and TNF. PMID- 2310782 TI - Trajectory formation of arm movement by cascade neural network model based on minimum torque-change criterion. AB - We proposed that the trajectory followed by human subject arms tended to minimize the time integral of the square of the rate of change of torque (Uno et al. 1987). This minimum torque-change model predicted and reproduced human multi joint movement data quite well (Uno et al. 1989). Here, we propose a neural network model for trajectory formation based on the minimum torque-change criterion. Basic ideas of information representation and algorithm are (i) spatial representation of time, (ii) learning of forward dynamics and kinetics model and (iii) relaxation computation based on the acquired model. The model can resolve ill-posed inverse kinematics and inverse dynamics problems for redundant controlled object as well as ill-posed trajectory formation problems. By computer simulation, we show that the model can produce a multi-joint arm trajectory while avoiding obstacles or passing through viapoints. PMID- 2310783 TI - Reticular activation and the dynamics of neuronal networks. AB - It is postulated that during arousal the cortical system is driven by a spatially and temporally noisy signal arising from non-specific reticulo-cortical pathways. An elementary unit of cortical neuroanatomy is assumed, which permits non-linear dynamics to be represented by stochastic linear equations. Under these assumptions the resonant modes of the system of cortical dendrites approach thermodynamic equilibrium. Specific sensory signals perturb the dendritic system about equilibrium, generate low frequency, linear, non-dispersive waves corresponding to the EEG, which in turn regulate action potential sequences, and instantiate internal inputs to the dendritic field. A large and distributed memory capacity in axo-synaptic couplings, resistance to interference between functionally separate logical operations, and a very large next-state function set emerge as properties of the network. The model is able to explain the close association of the EEG with cognition, the channel of low capacity corresponding to the field of immediate attention, the low overall correlation of action potentials with EEG, and specificity of action potentials in some neurons during particular cognitive activity. Predictions made from hypothesis include features of thermal equilibrium in EEG (determinable by autoregression) and expectation that the cortical evoked response can be accounted for as the response to a sensory impulse of specific time characteristics. PMID- 2310785 TI - Postural dynamics in the standing human. AB - The purpose of this study was to develop a mathematical model of the linkage dynamics in upright standing, and to use this model to study output principles for postural control. The standing human was modelled in the sagittal plane as a three-segment linkage. Mechanical disturbances were simulated as forces which could be applied at various points in this linkage. An iterative approach was used to find joint torque combinations which would restore balance within 80 ms of these mechanical disturbances. The model predicted that a specific proportional relationship was necessary between the hip, knee and ankle torques in order for balance to be restored. This proportional relationship was shown to be a function of the model structure, but independent of the location, direction and amplitude of the disturbance. These predictions were tested experimentally. A disturbance apparatus was designed to apply an impulsive force to the subjects. The joint torque responses of the subjects were in quantitative agreement with the predictions of the model. The results suggest that a fixed relationship between joint torques may be required to restore balance, and this fixed relationship may make the task of postural control simpler for the nervous system. PMID- 2310784 TI - Influence of the mechanical properties of a manipulandum on human operator dynamics. 1. Elastic stiffness. AB - An active servo-system was used to change the stiffness of a manipulandum used in a position-control pursuit-tracking task. The elastic stiffness of the manipulandum connected to the forearm was set by a computer at one of five levels ranging from 0 N/m to 2000 N/m. Subjects were required to track, either by moving their forearm or by generating a force isometrically, a visually presented target whose position changed randomly every second for 100 s. Nonparametric and parametric impulse response functions were calculated between the input (target) and output (force or position) in each tracking condition, and revealed that for all subjects force control was faster than position control when the stiffness of the manipulandum was set at 0 N/m. Subjects were also consistently faster in reaching the target when the stiffness was greater than zero, and were more accurate (steady-state response) when the stiffness of the manipulandum was set at lower rather than higher amplitudes. The parametric impulse response functions revealed that the human operator system was underdamped (0.7) with a natural frequency of approximately 8 rad/s. These findings were interpreted in terms of the responses of the various subsystems (visual, cognitive, contractile, limb mechanics) that comprise the human operator's response. PMID- 2310786 TI - Postural dynamics of walking in humans. AB - The dynamics of postural control in human biped locomotion were studied using (1) a model, and (2) experimentally applied impulsive force disturbances. The model was planar, and contained five rigid segments, articulating at frictionless pin joints. The model was used to identify joint torque combinations which would successfully correct for an impulsive force disturbance applied at different points in the walking cycle. The simulation results suggested that (1) early responses (within 80 ms) can be effective in compensating for impulsive disturbances, (2) the same strategies which successfully counteract similar disturbances during quiet standing are also effective in certain phases of the walking cycle, (3) modifications in the response strategies are needed to accommodate differences in the dynamics over the stride cycle, and (4) the swing leg is ineffective in compensating for disturbances in the short term. These model predictions were tested experimentally. Subject responses to an impulsive force disturbance applied during walking were studied. The electromyographic results generally support the model predictions. PMID- 2310787 TI - Compliant characteristics of single joints: preservation of equifinality with phasic reactions. AB - Electromyograms (EMGs) of elbow flexors and extensors, elbow joint angle and torque were recorded in healthy subjects in the "do not react voluntarily" paradigm. Random loading and unloading torque perturbations of different rise times (Tr) were applied. Perturbations with Tr less than 300 ms evoke a phasic increase (in case of loading) or decrease (in case of unloading) in the flexor EMGs. The shortest EMG latency of about 30 ms was observed with very rapid perturbations (Tr less or equal to 20 ms). Smooth torque changes (Tr of 500-800 ms) were not accompanied by noticeable phasic reactions. Two types of the compliant characteristics were recorded: those with a zone of relatively high stiffness at the starting point ("S-shaped" curves) and those with a relatively constant stiffness. The presence or absence of the S-shape does not depend on Tr and therefore, does not seem to depend on phasic reflex or triggered reactions. In some of the subjects who were tested twice with an intervals of 2 months, the form of the compliant characteristics changed. This finding suggests that presence or absence of the S-shape can depend upon the subject's ability to follow the "do not react voluntarily" instruction. The invariance of the compliant characteristics in the presence or absence of reflex reactions can be regarded as an example of equifinality in a case of transient perturbations generated within the motor control system. PMID- 2310788 TI - A model of olfactory adaptation and sensitivity enhancement in the olfactory bulb. AB - It has been suggested that the olfactory bulb, the first processing center after the sensory cells in the olfactory pathway, plays a role in olfactory adaptation, odor sensitivity enhancement by motivation and other olfactory psychophysical phenomena. In a mathematical model based on the bulbar anatomy and physiology, the inputs from the higher olfactory centers to the inhibitory cells in the bulb are shown to be able to modulate the response, and thus the sensitivity of the bulb to specific odor inputs. It follows that the bulb can decrease its sensitivity to a pre-existing and detected odor (adaptation) while remaining sensitive to new odors, or increase its sensitivity to interested searching odors. Other olfactory psychophysical phenomena such as cross-adaptation etc. are discussed as well. PMID- 2310789 TI - Effect of postnatal hypoxia on ammonia metabolism during the early neonatal period in the rat. AB - The effect of experimental hypoxia on blood glutamine, glutamate, urea, ammonia, allantoin, hypoxanthine, xanthine, urate, orotate and lactate concentrations and on PO2, PCO2 and pH in term delivered newborn rats during the first 4 h after delivery were studied. Hypoxia increased blood glutamine, glutamate, allantoin and 'xanthines' (hypoxanthine + xanthine + uric acid) concentrations but decreased blood urea and ammonia concentrations. These results suggest that hypoxia inhibited ureogenesis by decreasing the ammonia available for urea synthesis. PMID- 2310790 TI - Vitamin A storage in lungs during perinatal development in the rat. AB - We examined the ontogeny of vitamin A storage in fetal and neonatal lungs during perinatal development in the rat. High-performance liquid chromatography was used to measure concentrations of vitamin A and its esters, retinyl palmitate and stearate, in various fetal and neonatal tissues at times ranging from gestational day 14 through 21, and from postnatal day 1 through 21. The data show that significant vitamin A storage occurs in the fetal lung during the latter one third of prenatal life. Depletion of these stores that begins before birth and continues into the early postnatal period suggests that the developing lung may be dependent on these local vitamin A stores during active growth and differentiation. The utilization of vitamin A stores in the developing lung appears to be independent of the liver stores of vitamin A. PMID- 2310791 TI - Maternal caffeine ingestion increases the tyrosine level in neonatal rat cerebrum. AB - The cerebral free amino acids in neonatal rats, from dams given 0.04% caffeine in the drinking fluid ad libitum before and/or during pregnancy throughout the lactational period, were examined on days 1, 5 and 10. Significantly reduced cerebral weight was observed on day 1 with a mean caffeine level of 7 micrograms/g wet weight. The tyrosine concentration in the cerebrum, but not that in the liver, was increased on days 1 and 5 with approximate mean caffeine levels of above 1.5-2.0 micrograms/g wet weight. The tyrosine level showed a positive correlation with the caffeine level in neonatal cerebrum only on day 1 in the group with caffeine ingestion after pregnancy. There was no significant increase in the fetal cerebral concentration of MOPEG-SO4 on day 5 with maternal caffeine. These results suggest that maternal caffeine disturbs the neonatal cerebrum through tyrosine and tyrosine hydroxylase, and then produces behavioral abnormalities in developing rats. PMID- 2310792 TI - Factors that influence the distention of immature lung with artificial surfactant. AB - The exogenous therapy of respiratory distress syndrome with artificial surfactants is controversial. In the present work we treated premature rabbits with artificial ultrasonic obtained surfactant suspensions [dipalmitoyldiphosphatidylcholine:dipalmitoyldiphosphatidylglyc erol (DPPC:DPPG) 7:3] in various physical conditions produced by changing the carrier (saline solution and amniotic fluid) or incubating at 41 degrees C. Nonincubated samples (S0) were nonactive, the best effect on alveolar distention being found after 8 h incubation (S8), while 16 h incubated samples (S16) were less effective. Liposomal size of the mixtures correlated with their effectiveness; small unilamellar liposomes were nonactive, large unilamellar ones were active and in presence of large multilamellar liposomes the tensioactive effect decreased. Fifty-one percent of the alveolar distention, evaluated by morphometry, was due to treatment and 11% was linearly related to body weight. The ponderal effect of body weight was mathematically excluded in order to obtain more uniform results; the resulting parameter was called true treatment influence on alveolar distention (TIAD). 15% of TIAD varied due to the carrier, with significantly better results when saline solution was used as a carrier. These findings question the hypothesis of the prevention of respiratory distress syndrome by means of intraamniotic injection of surfactants. PMID- 2310793 TI - Cardiorespiratory patterns in infants presenting with apparent life-threatening episodes. AB - A total of 305 infants presenting with apparent life-threatening events (ALE) were referred by their paediatricians and underwent 24-hour tape recordings of electrocardiogram and abdominal breathing movements (from a pressure capsule transducer). Seventy-seven of these infants, all full-term (greater than or equal to 37 weeks of gestation), were randomly selected, followed up for clinical outcome, and their recordings subjected to a detailed analysis of heart and respiratory rates and breathing patterns. Recordings on 157 age-matched, full term controls were similarly analysed for comparison purposes. One of the 77 patients suffering from ALE had a pre-existing neurodevelopmental problem, and 4 more cases showed this at follow-up, including 1 case whose ALE was subsequently diagnosed as originating from non-accidental injury. Compared with controls and as a group, the patients suffering from ALE showed higher numbers of apnoeic pauses (p less than 0.001), larger quantities of periodic breathing (p less than 0.01) and lower respiratory rates during regular breathing (p less than 0.01). PMID- 2310794 TI - Relationship of urinary anion gap to urinary ammonium excretion in the neonate. AB - The present study was undertaken to define the relationship of urinary anion gap (UAG = sodium plus potassium minus chloride) to urine ammonium concentration in preterm and full-term neonates with spontaneous and NH4Cl-induced metabolic acidosis. Studies were performed in 10 premature infants (mean birth weight: 1,618 g, gestational age: 30.8 weeks) weekly for 6 consecutive weeks, in 11 full term neonates (mean birth weight: 3,085 g, gestational age: 38.6 weeks) on the 7th day of life and in 25 older control infants (mean age: 6.5 months, body weight: 6,802 g) before and after NH4Cl-loading test. Blood acid-base parameters, plasma electrolyte concentrations, urine pH, ammonium, titratable acidity, bicarbonate, net acid and electrolyte concentrations were measured, UAG calculated. It was demonstrated that the significant reduction in plasma total CO2 content induced by NH4Cl administration and the subsequent elevation in urinary ammonium concentration was associated with some decrease of UAG in each group. In premature infants there was no relationship between urinary ammonium excretion and UAG during the first 2 weeks of life while from the 3rd week onward a significant negative correlation could be demonstrated. In one-week-old full term neonates UAG also tended to decline with increasing ammonium concentrations; this relationship, however, proved to be insignificant. In the older control infants urinary ammonium excretion was found to correlate negatively to UAG. It is concluded that due to marked dynamic changes in unmeasured ionic composition of neonatal urine UAG is not a valuable index of urinary ammonium excretion in newborn infants during the first weeks of life. PMID- 2310795 TI - Visual evoked potential correlates of positive/negative symptoms in schizophrenia. AB - Previous studies of schizophrenic patients have found evoked potential (EP) correlates of clinical symptomatology, including EP differences between subtypes of schizophrenia. In the current study, 14 medicated male schizophrenics underwent flash visual evoked potentials (VEP) and were clinically rated for positive and negative symptoms. We tested the hypothesis that positive symptoms would be associated with VEP latency reduction and negative symptoms with latency prolongation. Patients were divided into predominantly positive symptom and predominantly negative symptom groups using a combination of positive and negative symptom ratings. Patients with predominantly positive symptoms exhibited reduced latencies when compared with predominantly negative symptom patients. Similarly, significant negative correlations between positive symptom ratings and P200 latency variables were found. Correlations between negative symptom measures and P200 latencies (in the opposite direction) were also noted, but were less significant. These relationships persisted when confounders were statistically controlled for. The results are consistent with previous findings of evoked potential correlates of clinical symptomatology, especially those finding EP latency correlates of psychosis severity and affective blunting. The findings are discussed in relationship to concepts relevant to psychosis, including arousal, sensory gating, and the dopamine hypothesis. PMID- 2310796 TI - Elevated serum lactate following hyperventilation during glucose infusion in panic disorder. AB - Early investigators reported that patients with anxiety syndromes associated with panic attacks produced more lactate during exercise than control subjects. These studies suggested a metabolic difference between patients and controls. However, the possibility that patients were simply less fit than controls could not be excluded. In this study, serum lactate was measured in panic disorder patients in response to a metabolic challenge not involving exercise. Voluntary hyperventilation during iatrogenic hyperglycemia led to an increase in serum lactate. The increase in serum lactate was significantly greater in panic disorder patients than in controls. Hyperventilation provoked panic attacks in 4 of 8 patients and none in 6 controls. There was no evidence of a relationship between the increase in lactate or the associated decrease in phosphate and the level of anxiety produced by this procedure. PMID- 2310797 TI - Psychophysiological correlates of posttraumatic stress disorder in Vietnam veterans. AB - We measured event-related brain potential (ERP) component amplitudes and heart rate (HR) to four intensities of randomly presented tones in two matched groups of drug-free male Vietnam veterans: 12 patients diagnosed with posttraumatic stress disorder (PTSD) and 6 normal combat veterans. Subjects were evaluated with structured diagnostic interviews and anxiety and depression rating scales. We found a significant group X intensity interaction for P2 peak amplitude at CZ. Subjects were classified as augmenters or reducers: positive P2 slopes as a function of stimulus intensity implying augmentation and negative slopes implying reduction. Nine of 12 PTSD subjects were reducers (sensitivity of 75%) and 5 of 6 normals were augmenters (specificity of 83.3%). By the third and fourth second following tone onset, the mean HR of PTSD subjects increased more than twice that of the normals. HR change scores were significantly responsive to the manipulation of stimulus intensity and to the difference between our two groups. P2 reduction differentiates Vietnam veterans with combat-related PTSD from combat veteran controls, and PTSD subjects are more autonomically arousable than their combat veteran peers. PMID- 2310798 TI - Hirsutism in women with chronic psychiatric illness. PMID- 2310799 TI - Fluoxetine in refractory depression. PMID- 2310800 TI - Rhythmic movements of chronic akathisia. PMID- 2310801 TI - The black hole of trauma. PMID- 2310802 TI - Increased production of thyroxine and inappropriately elevated serum thyrotropin in levels in endogenous depression. AB - The increased serum thyroxine (T4) levels in endogenous depression (ED) might be due to an increased production or a reduced degradation of T4. We therefore performed turnover studies of radiolabeled T4 and 3,5,3'-triiodothyronine (T3) in 6 patients with ED and 8 age-matched healthy controls. In ED, the median daily production of T4 was 130 nmol/day/70 kg, (range 100-186 nmol/day/70 kg) and elevated compared to control values which were 99 nmol/day/70 kg (range 85-142 nmol/day/70 kg) (p less than 0.05), whereas that of T3 was similar in the two groups. Serum thyrotropin (TSH) levels (0.90 mU/liter, 0.18-2.15 mU/liter) were elevated in ED compared to a group of 7 L-T4-treated hypothyroid subjects with similar production and serum levels of T4 and T3 (0.11 mU/liter, 0.07-1.10 mU/liter) (p less than 0.02). The data show that increased serum T4 levels in ED are secondary to an increased thyroidal production of T4, which is at least partly due to inappropriately high serum TSH levels. PMID- 2310803 TI - EEG sleep studies in "pure" primary alcoholism during subacute withdrawal: relationships to normal controls, age, and other clinical variables. AB - Electroencephalogram (EEG) sleep recordings were compared in 34 normal controls and 31 inpatients with relatively pure primary alcoholism who had been abstinent for about 17 days. Compared with normal controls, primary alcoholics took longer to fall asleep, slept less, and had poor sleep efficiency. Sleep loss reflected reduced non-rapid eye movement (NREM) sleep, especially stage 2 sleep, stage 4 sleep, and total delta (stage 3 and 4) sleep. Alcoholic patients had higher REM density of the first REM period. Sleep deteriorated with age in both normal controls and patients, with younger alcoholics showing sleep patterns typical of older controls. Among other clinical-demographic variables examined, the shorter the duration of sobriety at the time of the study, the later patients went to bed and fell asleep. The number of drinks per drinking day in the 3 months before admission was directly related to the duration of the first REM period. In addition, the maximum number of withdrawal symptoms the patient had ever experienced was inversely related to the amount of delta sleep. Sleep measures were not correlated with depression rating, liver enzymes, or other measures of alcohol consumption. PMID- 2310804 TI - 5HT2 receptor changes in major depression. AB - The 5HT2 receptor has been studied using quantitative tritium film autoradiography in the postmortem frontal cortex of 15 cases suffering from major depression and controls, matched for age, gender, postmortem delay, and storage time. In unmedicated depressives there was a significant increase in 5HT2 receptor binding over matched control values. Antidepressant-treated depressives dying while depressed had 5HT2 receptor densities not significantly different from control values. Depressives dying euthymic, (i.e., recovered) showed a marked reduction in 5HT2 receptor binding when compared with controls. A tentative hierarchy of 5HT2 receptors in affective states is proposed. PMID- 2310805 TI - A reexamination of the relationship between growth hormone secretion and slow wave sleep using delta wave analysis. AB - Sleep onset growth hormone secretion is a reliable and reproducible finding in young adults and children. Secretion typically occurs during the first non-REM period of sleep and, despite some evidence to the contrary, growth hormone secretion has frequently been associated with the first period of slow wave sleep. By measuring delta wave activity (0.5-2 Hz) instead of slow wave sleep and, accounting for the within subject variability, it has not been possible to demonstrate a consistent or statistically significant linear relationship between delta wave activity and sleep-related growth hormone secretion. This suggests the presence of more complex mediating factors and the possibility that sleep onset and growth hormone secretion are two separate processes which are independently stimulated by events associated with sleep onset. PMID- 2310806 TI - Plasma catecholamine metabolites in schizophrenics: evidence for the two-subtype concept. AB - Plasma homovanillic acid (pHVA) and plasma methoxyhydroxyphenyl glycol (pMHPG), as well as plasma haloperidol, were measured in 33 schizophrenic patients before and during 6 weeks of haloperidol treatment. Good responders had higher baseline pHVA values compared with poor responders (17.4 +/- 8.8 ng/ml, n = 22 versus 11.4 +/- 5.0 ng/ml, n = 11, p less than 0.05). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Differential pHVA changes during treatment were also found between good and poor responders. Within the good responder group, a significant decline in pHVA over time was found. By contrast, pHVA showed a transient increase in the poor responder group. Plasma MHPG changes showed a similar pattern during treatment in good responders, although no significant differences in baseline values were found between the good (n = 13) and poor (n = 9) responders, and pMHPG showed no change during treatment in poor responders. Significant correlations between baseline pHVA and pMHPG values were found in 22 patients. Good responders and poor responders did not differ significantly in terms of age, duration of illness, severity of presenting symptoms, haloperidol dose, or plasma drug concentration. Two hypothetical subtypes of schizophrenia and both dopamine and norepinephrine systems involved in schizophrenic psychopathology are proposed. PMID- 2310807 TI - Sensory gating deficits in psychiatric inpatients: relation to catecholamine metabolites in different diagnostic groups. AB - Acutely ill psychiatric inpatients were examined for a deficit in sensory gating, measured as failure to suppress the P50 wave of the auditory-evoked response to the second of paired stimuli. Previously, we had found that in mania, this sensory gating deficit is correlated with increased plasma-free levels of the noradrenergic metabolite 3-methoxy, 4-hydroxyphenylglycol (pMHPG), whereas in schizophrenia, there is no correlation with catecholamine metabolism. To assess the generalizability of these findings, we examined inpatients with a broader range of diagnoses, including those with multiple DSM III-R Axis I, II, and III diagnoses. The patients were grouped into three diagnostic spectra for analysis: schizophrenic, manic, and depressive. In the schizophrenic patients, there was no relationship between pMHPG or other catecholamine metabolites and the sensory gating deficit. In manic patients, however, a positive correlation between pMHPG level and the sensory gating deficit was again observed. This relationship did not extend to the depressive patients, who uniquely showed sensory gating deficits that correlated negatively with the severity of their illness. The data suggest that sensory gating deficits are common to these three diagnostic spectra, but the deficits in each group have different relationships to catecholamine metabolism and symptom severity that may reflect differences in the underlying neuronal pathophysiology of these illnesses. PMID- 2310808 TI - Cognitive performance in patients with bulimia nervosa: relationship to intermittent starvation. PMID- 2310809 TI - Effects of lithium on auditory evoked potentials in healthy subjects. PMID- 2310810 TI - Local alteration in adenylate cyclase activity and stimulation response at implantation site in rabbit endometrium during early pregnancy. AB - Adenylate cyclase activity and its hormonal stimulation were measured in endometrial tissue, and sex steroid levels were quantified in uterine tissue collected from pregnant and estrous rabbits. The tissues from pregnant animals were separated into implantation (ES) and interimplantation (IES) sites. Adenylate cyclase activity was measured in broken cell preparations by enzymatic conversion of alpha-32P-adenosine triphosphate (ATP) into 32P-cyclic adenosine 3', 5'-monophosphate using Mg2(+)-ATP as a substrate. The activity was measured with no addition (basal) and after stimulation with guanosine triphosphate (GTP), NaF, or increasing doses (1 nM to 100 microM) of isoproterenol (ISO) and prostaglandin E2 (PGE2). The presence of GTP was necessary to observe a stimulation by ISO and PGE2. During pregnancy, adenylate cyclase activity was reduced compared to activity at estrus on Day 6.5 (IES and ES) and on Day 9 (IES); however, it reached its highest level at ES (Day 9). The regulation of isoproterenol response followed a similar pattern. Dose responses to PGE2 were markedly affected by physiological status. The response was higher during pregnancy than at estrus, and response (percent of GTP), as well as sensitivity, was higher in IES than in ES on Day 6.5 and even greater on Day 9. The levels of estradiol (E2) were reduced during pregnancy, but comparable in ES and IES; however, progesterone (P) levels were reduced in ES, and the E2/P ratio was significantly higher (p less than 0.01) in ES (15 +/- 1, 17 +/- 2) than in IES (8 +/- 1, 6 +/- 0.8) on Days 6.5 and 9, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310811 TI - Birth of normal calves resulting from bovine oocytes matured, fertilized, and cultured with cumulus cells in vitro up to the blastocyst stage. AB - Bovine oocytes matured in vitro were fertilized in high proportions (92% of matured oocytes) by sperm capacitated with Ca ionophore A23187. Eight percent of inseminated oocytes that were denuded 96 h after insemination developed to the morula stage when cultured for 6-120 h after insemination with cumulus cells from the original oocytes. Inseminated oocytes denuded 96 h after insemination developed to the blastocyst stage when cultured with or without cumulus cells or in the conditioned medium from 96 h to 168-216 h after insemination (9.0%, 8.1%, and 6.8% of inseminated oocytes respectively). Six frozen-thawed blastocysts were transferred nonsurgically to 3 recipients (2 embryos/recipient). Two of the 3 recipients became pregnant, with one delivering live twins at term. Seven fresh blastocysts were transferred nonsurgically to 6 recipients (1-2 embryos/recipient). Three of the 6 recipients became pregnant, with 2 delivering live calves. PMID- 2310812 TI - Implantation delay and anti-deciduogenic activity in the rat by the anti androgen, hydroxyflutamide. AB - Studies were undertaken to determine whether the anti-androgen, hydroxyflutamide, has anti-progestagenic activity by using implantation, maintenance of pregnancy, and decidualization as end points. Prepubertal rats were induced to ovulate with the injection of 4 IU pregnant mare's serum gonadotropin and allowed to mate. Mated females were assigned randomly to various treatment groups. Beginning at 0800 h on Day 4 of pregnancy and at 12-h intervals thereafter, rats received a series of 6 s.c. injections of 5 mg hydroxyflutamide in oil, or oil only. Localized changes in endometrial vascular permeability, indicative of implantation, were assessed on Days 6 and 8 of pregnancy, after an injection of Evans blue dye. By Day 6, implantation has been initiated in the vehicle-treated rats, but not in hydroxyflutamide-treated rats. Hydroxyflutamide treatment was terminated on Day 6, and implantation was initiated by Day 8. The weights of uterine dye sites in hydroxyflutamide-treated rats on Day 8 were similar to those in vehicle-treated rats on Day 6. The number of fetuses and placentae were similar in all groups on Day 19. The weights of fetuses in both hydroxyflutamide treated and hydroxyflutamide + progesterone-treated rats were similar and significantly lower than those in control rats. Although there were no significant differences between vehicle-treated or hydroxyflutamide-treated rats in the proportion of rats delivering and litter size, the hydroxyflutamide treated rats delivered pups a mean of one day later than did the controls. Endometrial decidualization in ovariectomized, steroid-treated rats, following artificial stimuli, was significantly suppressed in hydroxyflutamide-treated rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310813 TI - Ultrastructural localization of cytochrome P-450scc in the bovine placentome using protein A-gold technique. AB - We have previously reported that the steroidogenic activity of the bovine placentome is stimulated by a calcium-mediated, cyclic nucleotide-independent mechanism and that this steroidogenesis is limited by the availability of sterol substrate to the side-chain cleavage enzyme. We have recently established that the antibody against bovine adrenal cytochrome P-450 cholesterol side-chain cleavage enzyme (P-450scc) can be used to specifically detect P-450scc in both bovine placentome and corpus luteum. In the present study, we used an immunogold technique to localize the P-450scc in the bovine placentome by electron microscopy. The mononucleate cell of the cotyledon showed both giant and normal sized mitochondria, with the latter, predominating. Both mitochondrial types found in the mononucleate cells clearly displayed gold particles located on the cristae; in contrast, these particles were absent in the binucleate cells. It is worth noting that giant mitochondria were found exclusively in the placental mononucleate cells in both the fetal and maternal sites but not in the binucleate cells. These findings suggest that the cholesterol side-chain cleavage enzyme is present in bovine cotyledon cells, primarily in mononucleate cells. The variations in P-450scc immunoreactivity among different cells of the placenta are suggestive of different steroidogenetic capacities of the cells. PMID- 2310814 TI - Physiological and immunocytochemical evidence for a new concept of blood flow regulation in the corpus luteum. AB - To explain the high rate of blood flow in the corpus luteum, we hypothesize that luteal blood vessels offer minimal resistance to flow and are incapable of vasomotion. This hypothesis was tested in rabbits at mid-pseudopregnancy by measuring blood flow in the corpus luteum and ovarian stroma with tracer-labeled microspheres at three levels of arterial blood pressure, which was manipulated by constricting the aorta above the ovarian artery. In addition, the distribution of vascular smooth muscle in the ovary was evaluated with morphological and immunocytochemical techniques. Decreases in arterial pressure were paralleled by reductions in blood flow in the corpus luteum, whereas ovarian stromal blood flow was unchanged. Consistent with our hypothesis, there was no change in the low level of vascular resistance offered by blood vessels in the corpus luteum, supporting the view that they are maximally dilated and incapable of autoregulation. Morphologically, the vessels within the corpus luteum appeared as large sinusoidal capillaries without smooth muscle, providing an anatomical explanation for the lack of vasomotor control demonstrated physiologically. The absence of vascular smooth muscle was confirmed with immunocytochemistry using an antibody against the muscle-specific intermediate filament, desmin. The fluorescein-labeled antibody decorated arteries and arterioles within the ovarian stroma and near the capsule of the corpus luteum, but did not decorate vessels in the corpus luteum of pseudopregnancy, providing additional evidence that the vessels of the corpus luteum lack the smooth muscle investment necessary to change vascular caliber. From these findings, we have proposed a novel scheme to explain intraovarian blood flow regulation. Vascular resistance in the ovarian stroma, as in most tissues, is acutely regulated by dilation or constriction of intratissue arterioles. In contrast, vascular resistance within the corpus luteum is modeled as a relatively invariable parameter, fixed at a low level by the morphological characteristics of the luteal vasculature. Therefore, the corpus luteum operates on a linear (maximally "vasodilated") pressure-flow curve, does not actively regulate intratissue blood flow, and is subject to acute regulation of perfusion only through changes in extra-luteal vessels. PMID- 2310815 TI - Morphological features of principal cells in the ovine epididymis: a quantitative and qualitative study. AB - Functions of the epididymis differ by region, and this may be reflected in epithelial structure. Therefore, tissues from the initial segment (IS), proximal and central caput (PCap, CCap), and proximal and central corpus (PCor, CCor) epididymidis were examined by light and transmission electron microscopy. The proportion of principal cells in the epithelium was highest (p less than 0.05) in the CCap (74%) and lowest in the CCor (68%), whereas proportions of basal cells (25%), apical cells (1.4%), and white blood cells (2%) were similar in all regions. Volume density (VD) of the nucleus was lower (p less than 0.05) in principal cells in the IS (7%) than in other regions (10%). There was no regional difference in VD of the Golgi complex (14%) or endoplasmic reticulum (19%) in principal cells. The VD of mitochondria averaged 4% in the IS through CCap, but only 2.5% in PCor or CCor (p less than 0.05). The VD of clear vesicles + multivesicular bodies (8%) and dense vesicles (6%) were higher (p less than 0.05) in the CCap than in other regions (1% each), while there were more lipid droplets (12%) in the PCor than in other regions (less than or equal to 2%). Most quantitative differences in VD of organelles within principal cells were small even though significant. However, there were profound differences in the morphological features of the Golgi complex, endoplasmic reticulum, and mitochondria among regions. PMID- 2310816 TI - Biochemical and morphological characterization of the intra-acrosomal antigen SP 10 from human sperm. AB - The human sperm protein SP-10 was previously defined as a "primary vaccine candidate" by a World Health Organization Taskforce on Contraceptive Vaccines. By one- and two-dimensional immunoblots, we show that SP-10, extracted from ejaculated human sperm, demonstrated a polymorphism of immunogenic peptides from 18 to 34 kDa, a pattern that was conserved from individual to individual and was not altered by reducing agents. The majority of the antigenic peptides possessed isoelectric points of approximately 4.9. Immunocytochemistry on testis sections indicated that SP-10 was localized to round spermatids and spermatozoa within the adluminal compartment of the seminiferous epithelium. Immunofluorescence showed that SP-10 was not associated with the surface of acrosome-intact, ejaculated sperm. Light and electron microscopic immunocytochemistry localized SP-10 throughout the acrosome, and electron microscopic evidence demonstrated a bilaminar array in association with the inner aspect of the outer acrosomal membrane and the outer aspect of the inner acrosomal membrane. After induction of the acrosome reaction with the ionophore A23187, SP-10 remained displayed on the sperm head in association with the inner acrosomal membrane and equatorial segment. The results indicate that the MHS-10 monoclonal antibody may be used as a marker of acrosome development in the human and as a probe to evaluate acrosome status. The results also support the hypothesis that inhibition of sperm-egg interaction by anti-SP-10 monoclonal antibody may occur as a result of antigen exposure following the acrosome reaction. PMID- 2310817 TI - Transitions in trophectoderm cellular shape and cytoskeletal organization in the elongating pig blastocyst. AB - Changes in cellular shape and filamentous actin (f-actin) organization within the trophectoderm of pig embryos have been studied by fluorescence microscopy during the transitions from spherical to filamentous blastocysts. Cells comprising the trophectoderm of spherical, ovoid, tubular, and filamentous blastocysts are distinctive in their shape, size, and organization of membrane-associated f actin. Trophectodermal cells of spherical and ovoid embryos are both generally circular in shape. However, as the spherical embryo acquires an ovoid shape, uniformally distributed apical cell surface microvilli relocate to the apical intercellular margins of adjoining trophectodermal cells. Transitional modifications in cellular shape and f-actin organization are observed in tubular blastocysts when apical cell surface microvilli reappear. In elongating filamentous blastocysts, trophectodermal cells assume a spindle-shaped morphology. The f-actin associated with the apical surface is diminished whereas the associated with the basolateral membrane predominates, especially in constricted regions of the blastocyst. These observations, in conjunction with morphometric parameters of trophectodermal cells and whole blastocysts, are discussed in relation to the role of the actin cytoskeleton in processes that modify trophectodermal cell shape and function in the elongating pig blastocyst. PMID- 2310818 TI - Continuous exposure of Suffolk ewes to an equatorial photoperiod disrupts expression of the annual breeding season. AB - The objective was to determine if "clamping" ewes onto a 12L:12D photoperiod resulted in expression of circannual rhythms of reproductive activity. On 24 February, 1986, two groups of 6 yearling ewes each were placed in isolated adjacent photochambers under a 12L:12D photoperiod and controlled temperature. Six control ewes were kept outdoors. Blood samples taken thrice weekly were analyzed for progesterone. Data from Days 0-1056 are reported. The mean number of cycles by control and 12L:12D ewes did not differ (32.8 +/- 1.7 vs. 29.7 +/- 4.0). The ranges were 27-39 vs. 4-51, respectively. Ten 12L:12D ewes started cycling coincidentally or later than the controls, and then cycled either regularly or irregularly throughout the study. Two of the 12L:12D ewes cycled continuously. The mean number of cycles during the period 15 April-15 August (anestrus) in Years 1, 2, and 3 were 0.7, 0.7, 0.2 for controls versus 0.3, 5.1, and 4.5 for 12L:12D ewes. The mean number of cycles during the period 15 September-15 January (breeding season) in Years 1, 2, and 3 were 7.3, 7.7, and 7.3 for controls versus 2.8, 4.8, and 4.0 for 12L:12D ewes. All controls showed distinct, alternating annual periods of anestrus and ovarian cycles whereas only two 12L:12D ewes showed a similar pattern. Estrous cycles were distributed nonrandomly in all controls and in 2 ewes exposed to 12L:12D. In the 12L:12D ewes, melatonin concentrations rose immediately after the lights-off and fell immediately after on. Lengths of the luteal phases of the cycles did not differ between groups. In summary, estrous cycles of most ewes clamped on a 12L:12D photoperiod occurred throughout the year at variable intervals rather than in distinct breeding seasons. PMID- 2310819 TI - Glucocorticoids inhibit estradiol-mediated uterine growth: possible role of the uterine estradiol receptor. AB - Stress-related activation of the hypothalamic-pituitary-adrenal axis (HPA) is associated with suppression of the reproductive axis. This effect has been explained by findings indicating that corticotropin-releasing hormone suppresses hypothalamic gonadotropin-releasing hormone (GnRH) secretion via an opioid peptide-mediated mechanism, and that glucocorticoids suppress both GnRH and gonadotropin secretion and inhibit testosterone and estradiol production by the testis and ovary, respectively. To evaluate whether glucocorticoids suppress the effects of estradiol on its target tissues, we examined the ability of dexamethasone to inhibit estradiol-stimulated uterine and thymic growth in ovariectomized rats. Estradiol alone, given daily for 5 days, caused dose dependent uterine and thymic growth. Dexamethasone alone, given daily for 5 days, caused a dose-dependent decrease in body weight gain and in thymic growth. When estradiol and dexamethasone were administered simultaneously, however, body weight gain and thymic growth were also inhibited (p less than 0.05). Dexamethasone decreased estradiol-induced uterine cytosolic and nuclear estrogen receptor concentrations (E2 R0, p less than 0.05; E2nR0, respectively), but had no effect on estradiol-induced progesterone receptor concentrations (P4R0, p greater than 0.05). Levels of uterine glucocorticoid receptors were not affected by estrogen and/or dexamethasone treatment. These findings suggest that stress levels of glucocorticoids, administered over a 5-day interval, block the estradiol-stimulated growth of female sex hormone target tissues. This effect may be partially mediated by a glucocorticoid-induced decrease of the estradiol receptor concentration. Thus, another mechanism by which the HPA may influence reproductive function during stress is by a direct effect of glucocorticoids on the target tissues of sex steroids. PMID- 2310820 TI - Relationship between dilatation of the rat uterine cervix and a small dermatan sulfate proteoglycan. AB - Cervical linear circumference (lo), extensibility and rate of creep, and the content and concentration of collagen and proteoglycans were determined on uterine cervices of rats at different reproductive stages. The inner circumference increased from 9 +/- 3 (SD) mm at the nongravid stage to a maximum of 41 +/- 5 mm at term; a significant drop to 23 +/- 2 mm occurred by 4 h postpartum with a further drop to 18 +/- 4 mm by 1 day postpartum. The extensibility and rate of creep reached their maxima 1 day before term and returned to the nongravid value by 1 day postpartum. The small (Mr = 95,000) type II dermatan sulfate proteoglycan, the major cervical proteoglycan, increased from 43 +/- 6 micrograms per cervix at the nongravid stage to 196 +/- 33 micrograms at term. The amount of this proteoglycan decreased significantly by 35% to 126 +/- 5 micrograms within 4 h postpartum and declined further to 79 +/- 16 micrograms by 1 day postpartum. The total cervical collagen content increased less than 2-fold during pregnancy, from 3.5 +/- 0.5 to 6.3 +/- 0.7 mg; a decline to 5.8 mg by 1 day postpartum was not significant. The ratio of small proteoglycan: collagen increased 2.5-fold between the nongravid state and term, then returned to the nongravid value by 1 day postpartum. Significant correlations were found between the lo and the amount of small proteoglycan per cervix (r = 0.86; n = 69) and between lo and the ratio of small proteoglycan:collagen (r = 0.83; n = 50) when data from every reproductive stage were combined. A mechanism is proposed whereby the interaction of the proteoglycan with collagen fibers might alter mechanical properties and contribute to cervical dilatation and its rapid reversal. PMID- 2310821 TI - Oxytocin-stimulated inositol phosphate turnover in endometrium of ewes is influenced by stage of the estrous cycle, pregnancy, and intrauterine infusion of ovine conceptus secretory proteins. AB - Three experiments (Exp) assessed the influence of stage of the estrous cycle, pregnancy, and intrauterine infusion of ovine conceptus secretory proteins (oCSP) on turnover of inositol trisphosphate (the putative second-messenger for oxytocin stimulated secretion of prostaglandin F2 alpha) in ovine endometrium during luteolysis and maternal recognition of pregnancy. In Exp 1, endometrium was collected from 5 cyclic (Cy) and 6 pregnant (P) ewes on Day 16 after onset of estrus. In Exp 2, endometrium was collected from Day 12 Cy (n = 5), Day 12 P (n = 3), Day 16 Cy (n = 4), and Day 16 P (n = 3) ewes. In Exp 3, 12 Cy ewes were allotted randomly, in a 2 x 2 factorial arrangement, to receive serum protein (SP), or oCSP and estradiol-17 beta (E2), or vehicle treatments. Ewes were injected i.v. with 0.5 mg E2 or vehicle on Day 12 and received twice-daily infusions of 1.5 mg SP or oCSP (containing 25 micrograms ovine trophoblast protein-1 by radioimmunoassay [RIA]) + SP (1.5 mg total protein) into each uterine horn on Days 12, 13, and 14. Blood samples for RIA of plasma progesterone were collected on Days 10-15 (before treatment on each day) and endometrium was collected on Day 15. For each Exp, 100 mg endometrium was incubated, in duplicate, for 2 h with 10 microCi [3H] inositol and treated with 0 or 100 nM oxytocin (OT) for 20 min, then [3H]inositol mono-, bis-, and trisphosphates (IP1, IP2, and IP3, respectively) were quantified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310822 TI - Alpha-granule pool of glycoprotein IIb-IIIa in normal and pathologic platelets and megakaryocytes. AB - Using an immunogold staining technique and electron microscopy, we investigated the localization of the alpha-granule pool of glycoprotein (GP) IIb-IIIa in normal platelets and maturing megakaryocytes (MK), in pathologic platelets from a patient with type I Glanzmann's thrombasthenia (GT), and from three patients with the gray platelet syndrome (GPS). In normal resting platelets, GPIIb-IIIa was observed on the plasmatic side of the plasma membrane, the open canicular system (OCS) membranes, and along the internal face of the alpha-granule membrane. This location was found with three monospecific polyclonal antibodies: one anti-GPIIb IIIa antibody, the second specific for GPIIb, and the third specific for GPIIIa. After thrombin stimulation, the alpha-granule labeling disappeared whereas membrane labeling increased. Platelets from GT did not display labeling on plasma membranes, OCS membranes, or alpha-granule membranes. Platelets from the three patients with GPS displayed intense labeling of the plasma membrane and the OCS membrane, as well as the abnormal small alpha-granules and along the inside of large vacuoles (which contain the granule membrane protein [GMP]-140). In cultured immature MK from normal progenitors, both peptide components of GPIIb IIIa appeared in the Golgi saccules and vesicles, and in the small precursors of alpha-granules, labeling both their membranes and their matrix. It was then observed only on the membrane of the mature MK alpha-granules, although labeling was less consistent than on the platelet granules. The MK plasma membrane and demarcation membrane system also displayed GPIIb-IIIa labeling. In conclusion, this study demonstrates that GPIIb-IIIa is present on the internal face of the alpha-granule membranes of platelets (where it appears early during MK maturation) as well as in the abnormal alpha-granules of gray platelets; it is absent from GT type I platelets. PMID- 2310823 TI - Platelet factor 4 inhibits human megakaryocytopoiesis in vitro. AB - Platelet factor 4 (PF4) is a multifunctional protein specific to platelets, synthesized in megakaryocytes and stored in alpha granules. This report of our work shows that PF4 potently inhibits human megakaryocyte colony formation in vitro. Colony formation by megakaryocyte progenitor cells from normal bone marrows was studied using the plasma clot culture system and indirect immunoperoxidase staining. Nonadherent mononuclear cells were co-cultured with various concentrations (0 to 20 micrograms/mL) of highly purified human PF4. Statistically significant inhibition of three classes of megakaryocyte progenitor cells, the mixed colony forming unit-megakaryocytes (mCFU-MK), the burst forming unit-megakaryocytes (BFU-MK), and the colony forming unit-megakaryocytes (CFU MK), was seen at a PF4 concentration of 2.5 micrograms/mL or greater. PF4 had no effect on erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) colony formation except at high concentration (5 micrograms/mL for BFU-E and 10 micrograms/mL for CFU-GM). When a concentration of 5 micrograms/mL PF4 was added at various time points during marrow culture, a reduction of megakaryocyte colony formation also occurred. In the presence of PF4 2.5 micrograms or 5 micrograms/mL, the percentage of mature type of colonies was found to be decreased compared with cultures with no added PF4. These data demonstrate that PF4 inhibits both proliferation and maturation of megakaryocyte progenitor cells in vitro and suggest that PF4 may play a role in autoregulating human megakaryocytopoiesis. PMID- 2310824 TI - Mechanism of mast cell deficiency in mutant mice of mi/mi genotype: an analysis by co-culture of mast cells and fibroblasts. AB - Mutant mice of mi/mi genotype are osteopetrotic and are deficient in mast cells. The osteopetrosis of mi/mi mice can be cured by bone marrow transplantation from congenic normal (+/+) mice, and therefore, the cause of the osteopetrosis is attributed to a defect of osteoclasts. Since both osteoclasts and mast cells are the progeny of multipotential hematopoietic stem cells, we examined whether mast cells were defective in mi/mi mice. In spite of the deficiency of mast cells in tissues of mi/mi mice, mast cells did develop when spleen cells of mi/mi mice were cultured with pokeweed mitogen-stimulated spleen cell conditioned medium (PWM-SCM). The proliferative response of cultured mast cells (CMC) derived from mi/mi mice to PWM-SCM was comparable with that of CMC from +/+ mice. In contrast, when CMC were co-cultured with the NIH/3T3 fibroblast cell line in culture medium lacking PWM-SCM, only +/+ CMC entered into the S phase of the cell cycle and were maintained; mi/mi CMC gradually disappeared. Moreover, fibroblasts derived from the skin of mi/mi mice normally supported the proliferation of +/+ CMC. Thus, the mast cell deficiency of mi/mi mice appears to be due to the inability of mi/mi mast cells to respond to the proliferative stimulus presented by fibroblasts. PMID- 2310825 TI - In vitro establishment and characterization of a human megakaryoblastic cell line. AB - A human megakaryoblastic cell line, designated CHRF-288-11, has been established in vitro through the use of adherent stromal cells in long-term human bone marrow culture. Long-term bone marrow cultures were required for the initial adaptation of the megakaryoblastic cells to culture conditions; however, once adapted, the cells were weaned from the stromal layer until they proliferated in the complete absence of any feeder layers. The seed cells for the establishment of this line were derived from a solid tumor; the cloned cell line derived from this tumor exhibits markers characteristic of megakaryocytes and platelets. Specifically, the cells express platelet peroxidase, platelet factor 4, and platelet Ca+(+) adenosine triphosphatase (ATPase), glycoprotein IIb-IIIa (CDw41), factor VIII antigen, and the MY7 (CD13) and MY9 (CD33) antigens. The cells do not express the erythroid markers glycophorin A and hemoglobin, the myeloid marker myeloperoxidase, nor markers specific for T and/or B cells. The established cell line produces both basic fibroblast growth factor and transforming growth factor beta, properties demonstrated previously for the solid tumor. The clonal cell population exhibited a unique, singular karyotype, indicating cellular homogeneity. The cells display a doubling time of approximately 33 hours in either 25% horse or calf serum. Treatment of the cells with 1 X 10(-8) mol/L phorbol 12-myristate 13-acetate (PMA) leads to the induction of multi-nucleation and hyperploidy in the cells, with approximately 35% of the cells exhibiting two or more nuclei per cell, and greater than 80% of the cells enlarging in size. The establishment of this unique cell line under defined culture conditions will be beneficial for the future study of megakaryocytic properties expressed by this cell line. PMID- 2310826 TI - Hemorrhagic sequelae of immune thrombocytopenic purpura in human immunodeficiency virus-infected hemophiliacs. AB - Clinical bleeding tendency and tests of immune function were studied prospectively in 11 human immunodeficiency virus (HIV)-infected hemophiliacs with immune thrombocytopenic purpura (ITP) and a platelet count less than 50,000/microL. These 11 patients represented 13% of a well-characterized cohort of 87 HIV + hemophiliacs. ITP developed a mean 3.5 years after seroconversion, mean platelet count at presentation was 36,000/microL (range 15,000 to 49,000/microL), and the mean age at seroconversion was 37.1 years. Nine patients (82%) suffered bleeding complications, including four with intracranial hemorrhage, which was fatal in three. At the onset of ITP, five had AIDS and six were asymptomatic. Mean T4 lymphocyte count at onset of ITP was 126 +/- 32/microL (range 5 to 267/microL). Sustained treatment responses occurred with intravenous gammaglobulin (2 of 2), one of whom spontaneously remitted, and with zidovudine (1 of 2), but not with steroids (0 of 6) or danazol (0 of 3). In conclusion, 13% of a cohort of HIV + hemophiliacs has developed ITP with platelets less than 50,000/microL, a significant proportion of whom (82%) have experienced bleeding complications. It is recommended that treatment for ITP in HIV + hemophiliacs be instituted once the platelet count falls below 50,000/microL in order to avoid serious hemorrhagic sequelae. PMID- 2310827 TI - Membrane expression of platelet calpain. AB - Platelet calpain has many platelet substrates, including external membrane proteins. We thus investigated whether platelet calpain II was associated with platelet membranes in unstimulated and thrombin-activated platelets. A monospecific, goat polyclonal antibody was reared to purified platelet calpain II. Sixteen whole platelet lysates were found to contain 4.5 +/- 0.7 micrograms calpain antigen II per 10(8) platelets (mean +/- SEM) as determined by a competitive enzyme-linked immunosorbent assay. Using the dipeptide fluorogenic substrate, Suc-Leu-Tyr-MCA, 17 human platelet lysates contained 3.6 +/- 0.4 micrograms calpain activity per 10(8) platelets. Platelet calpain II was associated with the Triton X-100 insoluble platelet cytoskeletons from both unstimulated and thrombin-activated platelets. When compared with the total cell content of platelet calpain II, calpain antigen (10% to 13%) and calpain activity (24% to 28%) was associated with platelet cytoskeletons in unstimulated and thrombin-activated platelets, respectively. On immunoblot, the heavy chain (80 Kd) of calpain II was detected in platelet cytoskeletons. Subcellular fractionation studies on both unstimulated and thrombin-activated platelets, revealed that half of the total platelet calpain II antigen was associated with cytosol, and the other half was associated with the membrane fraction. Platelet calpain II was not seen on the surface of unstimulated, paraformaldehyde fixed platelets by immunofluorescence. However, on thrombin-activated platelets, rim immunofluorescence was seen, indicating that activated platelets externalize their calpain. This observation was confirmed by the finding that about 2,000 molecules per platelet of an 125I-anti-calpain II Fab' specifically bound to thrombin-activated but not unstimulated platelets. Both dibucaine (1 mmol/L) and platelet activating factor (1.86 mumol/L) in the absence of external Ca++, but not collagen (5 micrograms/mL) or ionophore A23187 (2.5 mumol/L) in the absence of external Ca++, were also able to externalize platelet calpain II antigen, as indicated by a similar level of specific 125I-anti-calpain II Fab'-platelet binding. These combined studies indicate that platelet calpain II is a major protein, comprising 2% of total platelet protein, a substantial portion of which is membrane-associated. When platelets are activated by thrombin and platelet activating factor, calpain II antigen also becomes present on the external platelet surface. PMID- 2310828 TI - Analysis of rodent platelet glycoprotein IIb: evidence for evolutionarily conserved domains and alternative proteolytic processing. AB - Recently, the full-length primary amino acid sequence for human glycoproteins (GP) IIb and IIIa have been derived from their respective cDNAs. Potential functional domains within these proteins have been proposed based primarily on homology with similar domains in other proteins having known biologic function. To further understand the relationship between structure and function of the platelet fibrinogen receptor, we have begun comparative studies of the human GPIIb/IIIa receptor with the corresponding rodent receptor. The rodent rGPIIb/IIIa receptor differs from the human receptor, having low affinity for R.G.D-containing oligopeptides and not binding at all to the C-terminus of the gamma chain of human fibrinogen. We describe the structure of rodent platelet GPIIb derived from a combination of peptide sequencing, and cDNA and partial genomic DNA sequence analysis. The initial transcript is 1037 amino acid residues, having 78% amino acid identity with its 1039 residue human analog. Both heavy chains have the N-terminal sequence L.N.L.D, agreeing with the consensus derived from other integrin family alpha heavy chains. All 18 cysteine residues occur at positions conserved in human GPIIb and the vitronectin receptor alpha subunit VNR alpha. The putative calcium-binding domains of the GPIIbs have a high level of amino acid identity (92%), supporting the supposition that these regions have a critical biologic role. The final 48 C-terminal amino acid residues of the heavy chain of rodent GPIIb share only 56% identity with its human counterpart, and the proposed cleavage site of human GPIIb into its heavy and light chains is not present in the rodent sequence. Although we demonstrate that rodent GPIIb is split into two subunits during its maturation, this process either involves a different recognition sequence in the rodent or occurs at a different site. Finally, partial genomic DNA sequence analysis indicates that there are at least two rodent GPIIb genes: a normal gene, containing introns in positions similar to those in the human gene, and a processed pseudogene. The human haploid genome contains only a single GPIIb gene. PMID- 2310829 TI - Interleukin-1 induces interleukin-6 production in peripheral blood monocytes. AB - Interleukin-6 (IL-6), a multifunctional cytokine produced in monocytes, fibroblasts, endothelial cells, and keratinocytes, is induced by a variety of stimulating signals, including lipopolysaccharide (LPS), poly (I), poly (C), IL 1, tumor necrosis factor (TNF), and platelet-derived growth factor. Some of these signals induce IL-6 effectively only in one cell type, and this selectivity of induction may explain selectivity of biologic effects. In the present study, we show that IL-1 beta, previously known to be a potent inducer of IL-6 in fibroblasts, endothelial cells, and keratinocytes, but not in monocytes, is also a potent inducer of IL-6 in peripheral blood monocytes. High level IL-6 activity that could be neutralized by specific antibodies to IL-6 was detected in supernatants of IL-1-stimulated monocytes. Maximal induction required IL-1 concentrations of 10 ng/mL. As judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, IL-6 species of relative molecular mass of 19 to 26 Kd could be specifically immunoprecipitated from supernatants of IL-1-induced monocytes. Size heterogeneity is a reported feature of IL-6 produced in a variety of cell types, and monocyte-derived IL-6 induced by either IL-1 or LPS displayed similar size heterogeneity. The highly purified recombinant IL-1 beta preparation used contained little, if any, LPS. In addition, monocyte production of IL-6, induced by IL-1 beta, was specifically neutralized by anti-IL 1 beta antibodies, demonstrating that IL-1, rather than a contaminant in the IL-1 preparation, was responsible for IL-6 induction. A number of biologic activities have been ascribed both to IL-1 and IL-6. The finding that IL-1 induced IL-6 in monocytes may help in defining the spectrum of biologic activities of each of these interactive cytokines. PMID- 2310830 TI - Bryostatin 1, a unique biologic response modifier: anti-leukemic activity in vitro. AB - Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, has demonstrated both antineoplastic activity against the murine P388 leukemia line in vivo and stimulatory activity against mouse and human hematopoietic progenitors. We studied the effects of bryostatin 1 on the growth of human leukemias in vitro. Bryostatin 1 inhibited 1 to 4 logs of clonogenic leukemia cell growth from three of four leukemia cell lines. Bryostatin 1 also inhibited, by at least 1 log, the proliferation of clonogenic acute nonlymphocytic leukemia (ANLL) cells from 10 to 12 patients with newly diagnosed or relapsed ANLL. Maximal inhibition of leukemic growth occurred at 10(-9) to 10( 7) mol/L bryostatin 1. Interestingly, bryostatin 1 also inhibited the growth of hematopoietic progenitors from eight patients with myelodysplastic syndromes (MDS). Leukemia cells exposed to bryostatin 1 for up to 96 hours and then washed, demonstrated no substantial inhibition of clonogenic growth, indicating that the anti-leukemic effect of bryostatin 1 is cytostatic. The phorbol ester 12-0 tetradecanoylphorbol-13-acetate (TPA) produced more potent inhibition of clonogenic leukemia growth, and this inhibition was blocked by bryostatin 1. Thus, the anti-leukemic activity of bryostatin 1 may be mediated through activation of protein kinase C. Bryostatin 1 inhibits clonogenic leukemia cells at concentrations that stimulate normal hematopoietic progenitors. The differential effects of bryostatin 1 on normal and abnormal hematopoiesis suggest that bryostatin 1 may have value in the treatment of leukemias and MDS. PMID- 2310831 TI - Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation. AB - Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML. PMID- 2310832 TI - Allogeneic bone marrow transplantation for leukemia with marrow grafts depleted of lymphocytes by counterflow centrifugation. AB - Eighty consecutive patients were transplanted with human leukocyte antigen (HLA) identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI) with a low (4.1 +/ 0.3 cGy/min) or high (13.1 +/- 1.6 cGy/min) midline average dose rate. In 43 patients, cytosine-arabinoside or anthracyclines were added to the conditioning regimen. Immunoprophylaxis posttransplant consisted of methotrexate (MTX) alone, cyclosporine A (CsA) in combination with MTX, or CsA alone; two patients received no immunoprophylaxis at all. Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) greater than or equal to grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. Only three patients died of cytomegalovirus-interstitial pneumonitis. The projected 3-year probability of relapse was 30% (95% confidence interval [CI], range 8% to 53%) in transplants for AML in first complete remission (CR1), 35% (95% CI, 1% to 69%) after transplantation for ALL in CR1, and 38% (95% CI, 2% to 74%) after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% (95% CI, 35% to 77%) after transplantation for AML-CR1, 42% (95% CI, 16% to 69%) in patients transplanted for ALL-CR1, and 49% (95% CI, 18% to 80%) after transplantation for CML-CP1. After transplantation for AML-CR1, ALL-CR1, or CML-CP1, the median follow-up time for leukemia-free survivors was 31+, 30+, and 21+ months, respectively. Probabilities of relapse, survival, and LFS in AML-CR1 and ALL-CR1 transplants were comparable with those reported in recipients of untreated grafts. In patients transplanted for CML-CP1, probability of relapse was higher and probability of LFS was lower than in recipients of untreated grafts. In transplants for leukemia in CR1 and CP1, preparative regimen and immunoprophylaxis posttransplant were not associated significantly with the probability of acute GVHD greater than or equal to grade 2, extensive chronic GVHD, relapse, survival, or LFS. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2310833 TI - Cytolytic function of clonable T cells after human bone marrow transplantation. AB - We evaluated T-cell mediated lymphokine activated killer (LAK) function during the late (greater than 5 months) reconstitution phase after T cell-depleted allogeneic bone marrow transplantation (BMT) for hematologic malignancy. Since LAK cells are sustained by interleukin-2 (IL-2), we also investigated the ability of post-BMT T cells to produce IL-2. These functions were investigated at the clonal level. More than 200 T-cell clones from six long-term BMT recipients were generated and compared with 60 T-cell clones derived from two normal controls. Almost all the CD8+ clonal cultures from BMT recipients expressed cytolytic activity in a lectin-dependent cellular cytoxicity assay. Interestingly, a higher proportion of BMT recipient-derived cytolytic clones were able to mediate LAK activity in comparison with control clones (28% versus 4%, P less than .05). However, T-cell clones from BMT recipients, as opposed to control clones, were largely incapable of producing IL-2. Given the high proportions of post-BMT circulating CD8+ T cells, it appears that, in long-term BMT recipients, the precursors of nonspecific LAK effectors are present at above normal levels. However, their function may be defective in vivo due to poor IL-2 production. PMID- 2310834 TI - Bone marrow graft engineering by counterflow centrifugal elutriation: results of a phase I-II clinical trial. AB - In an attempt to reduce the incidence and severity of acute graft-versus-host disease (GVHD), we have decreased the number of bone marrow (BM) lymphocytes in the donor marrow graft before bone marrow transplantation (BMT) using counterflow centrifugal elutriation (CCE). In a phase I-II clinical trial, 23 patients received lymphocyte-depleted BM allografts from their HLA-identical, mixed lymphocyte culture (MLC)-nonreactive sibling donors. The patients entered in the study were deemed to be at high risk for treatment failure on the basis of age (greater than 30 years; median, 39 years) and the result of our skin explant assay predictive of acute GVHD. Patients predicted not to develop acute GVHD by this assay were excluded from this study. All patients received a standard lymphocyte dose of 0.5 x 10(6) morphologic lymphocytes per kilogram ideal body weight (IBW) in the marrow graft and were maintained on cyclosporine A (CsA) immunosuppression for 170 days after BMT. Prompt hematopoietic recovery occurred in 22 of 23 patients with a median time to an absolute neutrophil count (ANC) greater than or equal to 500/microL of 21 days. Donor cell engraftment was subsequently verified by cytogenetic and/or DNA analysis in all of 21 evaluable patients. No patient developed systemic acute GVHD. Only five (22%) developed cutaneous GVHD (clinical stage 1) that required steroid treatment, including one patient who failed to engraft. The median follow-up of the patients enrolled in this study is 14 months (range, 5 to 20 months). Actuarial survival 1 year after BMT is 83%. Thus, in two consecutive clinical trials using CCE to deplete donor BM of alloreactive lymphocytes (1.0 x 10(6) versus 0.5 x 10(6) lymphocytes/kg), we have demonstrated that the procedure does not interfere with BM engraftment and is effective in decreasing the incidence and severity of acute GVHD. Furthermore, comparison of these studies has revealed a differential dose response relationship between the number of graft lymphocytes, protection of engraftment, and induction of acute GVHD. Although there appears to be a modest relationship between lymphocyte dose and time to hematopoietic recovery, the 50% reduction in lymphocyte dose from that used in our previous trial resulted in a marked decrease in acute GVHD without compromising engraftment. PMID- 2310835 TI - A spontaneous mutation produced a novel elongated beta-globin chain structural variant (Hb Agnana) with a thalassemia-like phenotype. PMID- 2310836 TI - Effect of recombinant soluble CD4 on the in vitro growth of hematopoietic progenitor cells from AIDS patients. PMID- 2310837 TI - Rapid quantitative determination of epirubicin and its metabolites in plasma using high performance liquid chromatography and fluorescence detection. AB - A rapid sensitive and selective isocratic technique was developed for the analysis of plasma epirubicin and three of its known fluorescent metabolites epirubicinol, 4'-O-beta-D-glucuronyl-4'-epidoxorubicin and 4'-O-beta-D-glucuronyl 1,3-dihydro-4'-epidoxorubicin, with daunorubicin as an internal standard, by using high performance liquid chromatography (HPLC) with fluorescence detection and a 'Hypersil ODS' column. The drugs were easily and efficiently extracted with a Sep-Pak C18 cartridge and the mean recoveries were greater than 85%. Intraassay and Interassay coefficients of variation (plasma samples) were better than 8.25%. An example of pharmacokinetic study obtained in a cancer patient after intravenous injection of epirubicine is described. PMID- 2310838 TI - Determination of urinary tryptophan and its metabolites along the nicotinic acid pathway by high performance liquid chromatography with ultraviolet detection. AB - A fast and sensitive method is given for analysing urinary tryptophan and six of its metabolites on the nicotinic acid pathway. Kynurenine, tryptophan, 3 hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, kynurenic acid and xanthurenic acid were isocratically eluted and completely resolved with a mobile phase of acetonitrile + sodium acetate buffer, pH 4.76 (4:96, v/v). The flow rate was 0.8 mL/min at the beginning and was then linearly increased to 1.2 after 6 min; after 14 min the flow was augmented from 1.2 to 2 mL/min. The effluent was monitored with a variable UV detector set at 254 nm for the first five peaks and at 280 and 325 nm for the penultimate peak and final peak. Analytical recoveries of the compounds after deproteinization varied between 64% and 98%. The reported method should enable one to examine easily, extensively, quantitatively and routinely urinary tryptophan and the most important metabolites of the nicotinic acid pathway. PMID- 2310839 TI - The determination of total and unbound midazolam in human plasma. A comparison of high performance liquid chromatography, gas chromatography and gas chromatography/mass spectrometry. AB - Midazolam concentrations in patients' plasma was determined after extraction with high performance liquid chromatography (HPLC), gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). GC was selected for routine plasma assays in terms of selectivity, simplicity, precision, accuracy and sensitivity (0.02 microgram/mL); HPLC analysis was less sensitive (0.1 microgram/mL) than GC; GC/MS was used for analysis validation. Plasma protein binding of midazolam was determined by GC in patients' plasma after in vitro incubation with midazolam, ultrafiltration and extraction; 5% of the drug was unbound to plasma proteins. Midazolam distribution in lipoprotein fractions separated by ultracentrifugation of plasma obtained from patients on prolonged midazolam treatment was also assayed by GC. PMID- 2310840 TI - Optimization of an isocratic reversed phase liquid chromatographic system for the separation of fourteen steroids using factorial design and computer simulation. AB - An optimization strategy for an isocratic reversed phase high performance liquid chromatographic system (RP-HPLC) is described. Factorial design and a computer program are used to predict the retention time and resolution of fourteen steroids. An optimized rapid (less than 25 min) isocratic RP-HPLC system for the satisfactory separation of cortisone, cortisol, corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, 17 alpha-hydroxyprogesterone, progesterone, androstenedione, testosterone, estrone, estradiol, estriol, prednisone acetate and dexamethasone acetate has been developed using this strategy through eight experiments. PMID- 2310841 TI - Application of reversed phase high performance liquid chromatography to the analysis of sulphidopeptide leukotrienes in pig bile. AB - Reversed phase HPLC methodology has been developed for separation of peptide leukotrienes and indomethacin in porcine bile. Reproducible recoveries were obtained using radioactive leukotrienes ([3H]LTC4, 57.1 +/- 2.5%; [3H]LTE4, 62.7 +/- 1.9%; [3H]LTD4, 54.3 +/- 2.7%). Radioimmunoassay of column eluant demonstrated that as little as 300 pg of exogenous leukotrienes could be measured in bile fluids, with similar recoveries. Analysis of bile sampled 60-90 min after initiation of experimental endotoxic shock in indomethacin treated pigs revealed a leukotriene concentration of 5.24 +/- 1.16 ng/mL(LTD4). This was significantly greater (p less than 0.05, n = 3) than that observed in samples collected prior to endotoxin (0.42 +/- 0.23 ng/mL), or from untreated animals (0.85 +/- 0.51 ng/mL). This method is thus applicable to investigation of the role of 5 lipoxygenase products in porcine models of human disease, including shock conditions such as endotoxaemia, during cyclooxygenase inhibition by indomethacin. PMID- 2310842 TI - Studies on the metabolism of lappaconitine in humans. Identification of the metabolites of lappaconitine in human urine by high performance liquid chromatography. AB - The metabolites of lappaconitine in the urine of humans having been previously administered intramuscularly with lappaconitine hydrobromide were studied using high performance liquid chromatography with electrochemical and ultraviolet detection. The urine was extracted by means of liquid- and solid-phase extractions. Each of the metabolites of lappaconitine was purified by high performance liquid chromatography on a reversed phase column and identified on the basis of the chromatographic behaviour and the detector response. It was proved that lappaconitine, N-deacetyl-16-O-demethyllappaconitine and N deacetyllappaconitine were excreted in urine from humans receiving lappaconitine. PMID- 2310843 TI - Alcohol use and the appearance of alcohol problems among first offender drunk drivers. AB - Drinking patterns among first offender drunk drivers are described using two quantitative dimensions, drinking frequency (the number of occasions on which alcohol was consumed) and continuation (the probability that the drinker will go on to drink several drinks once one drink has been consumed). The two independent dimensions of drinking patterns are shown to be differentially related to demographic characteristics of the subject population. Further, the patterns of drinking described by the two dimensions predict the appearance of alcohol related problems. It is demonstrated that demographic characteristics of the sample are also related to reports of alcohol problems independent of drinking frequency and continuation. PMID- 2310844 TI - Giving ethanol to alcoholics in a research setting: its effect on compliance with disulfiram treatment. AB - In order to evaluate the effect of experimental ethanol administration on disulfiram compliance, a 6-month follow-up study was conducted with inpatient alcoholics. Two groups of patients were studied. Though not randomly assigned, the groups were matched on a variety of demographic and alcoholic-related variables. One group (N = 15) received ethanol in a laboratory-based study while the other group (N = 21) underwent treatment as usual. Days of disulfiram use did not differ between groups at follow-up. Studies concerning compliance with disulfiram support the validity of this measure as an indicator of treatment outcome. Our findings are consistent with other studies of the effect of experimental administration of ethanol to alcoholics, in that there were no immediate adverse effects and treatment outcome did not appear to suffer as a consequence of ethanol exposure. PMID- 2310845 TI - Public opinion on alcohol policies. AB - In recent years leading authorities and organizations have been recommending policies to combat alcohol abuse. These policies range from restrictions on availability to curbs on drinking and driving. However, the policies have not been presented in any priority order, nor is it clear how acceptable they will be to the general public. This report sets out public opinion on 21 key policies and looks at recent changes in public support in this area. It shows that there are a wide range of policies on alcohol which are well supported by the general public. It seems that the vast majority of both drinkers and non-drinkers would like to see more detailed labelling on alcoholic drinks, further action in the area of drinking and driving, the promotion of alternatives to alcohol in pubs, a levy on alcohol advertising, bans on the sale of alcohol at a variety of sports meetings, more alcohol education in schools and stricter enforcement of the laws on under age drinking. In addition, the survey reveals greater public support for restrictions on the promotion of alcohol and the introduction of random breath testing, than had been found one year previously. It is suggested that these findings could be used for setting an agenda on the implementation of policies to reduce alcohol abuse. PMID- 2310846 TI - Journal interview 27. Conversation with Philip Connell. PMID- 2310847 TI - A survey of general practitioners' opinion and attitude to drug addicts and addiction. AB - A survey was carried out to investigate general practitioners' attitude towards drug addicts and addiction. A questionnaire was sent to all GPs in the Norwich Health District and obtained an 87% response rate. A range of negative and positive attitudes was identified. The implications of these findings are discussed with particular reference to current government policy of encouraging GPs to extend their role in treating drug addiction. PMID- 2310848 TI - Heroin misusers: what they think of their general practitioners. AB - One hundred and sixteen heroin misusers were assessed at hospital clinics regarding their contact with General Practitioners (GPs), their routes of referral and their estimation of GP reaction to a consultation regarding heroin misuse. Thirty-nine (25%) had not previously contacted their GPs for drug misuse; 103 (89%) approached the specialized clinics through means other than a GP; the reported, or anticipated, responses concerning GP attitudes were generally unfavourable. Lack of training and support for GPs are remediable explanations for the findings. PMID- 2310849 TI - Alcohol histories in hospital: does the age and sex of the patient make a difference? PMID- 2310850 TI - A syndrome identical to the neuroleptic malignant syndrome induced by LSD and alcohol. PMID- 2310851 TI - Pharmaceutical heroin and 'chasing the dragon'. PMID- 2310852 TI - The practical business of treatment--8. The Edinburgh alcohol problems clinic. PMID- 2310853 TI - A systems approach to estimating the required capacity of alcohol treatment services. AB - This paper describes a model for estimating the required capacity of alcohol treatment systems at the local or regional level. Previous attempts at developing comprehensive forecasting models for addiction services are briefly described. The four steps followed in the development of the present model are then outlined. In many respects, the resulting model is specific to Ontario, Canada. However, the general approach, and many of the underlying concepts and assumptions, may have wider application in assessing the need for alcohol treatment services. PMID- 2310854 TI - The lure of masterstrokes: drug legalization. PMID- 2310855 TI - Home detoxification for problem drinkers: acceptability to clients, relatives, general practitioners and outcome after 60 days. AB - The value of a new Home Detoxification service was assessed in a variety of ways employing data collected from 41 clients of the service, their family and GP's. By 60 days from the start of treatment, 11 clients were abstinent, two were controlling their drinking with relatively few problems, 13 had 'improved', 14 were not 'improved' and one had an unknown outcome. Subsequent involvement in treatment by both clients and their partners was high in comparison with other studies. Significant predictors of 'Good' outcome included attendance for after care by client and by spouse/partner and a low Alcohol Problems Inventory score. High levels of satisfaction were expressed with the HD service by clients, their carers and GP's. The great majority of clients gave 'home' as their preferred place of treatment and nearly half claimed they would have been unwilling to accept hospital care. There was evidence of significant, though modest, shifts in GP's management practices towards less use of hospitals and greater use of the patient's home after 15 months of the programme. PMID- 2310856 TI - Types of life events and the onset of alcohol dependence. AB - Data concerning the occurrence of life events in the year before onset of alcohol dependence were collected from 23 patients recruited from a district general hospital. Both male and female alcohol dependent cases reported significantly more severe life events in the year preceding onset of the disorder than did members of a community comparison group over the same 12-month period. Events were also classified according to the dimensions of 'loss' and 'danger', and 'independence'. The study suggests that individuals may enter the initial stages of alcohol dependence in response to stressful life events. PMID- 2310857 TI - Family cohesion, expressiveness and conflict in alcoholic families. AB - This study estimated family cohesiveness, expressiveness, and conflict in a primary care sample of alcoholics and non-alcoholics with and without a family history of alcoholism. Subjects completed the NIMH Diagnostic Interview Schedule alcohol subscale, based on DSM-III criteria, and a family environment scale. Alcoholics with a family history of alcoholism (Alc+FH+) reported significantly less cohesion and expressiveness, and more conflict in their present families than did either non-alcoholics with a family history of alcoholism (Alc-FH+) or non-alcoholics with no family history of alcoholism (Alc-FH-). Non-alcoholics who grew up in alcoholic families (Alc-FH+) reported present family relationships similar to non-alcoholics with no family history of alcoholism (Alc-FH-). Results suggest a family history of alcoholism alone was not associated with differences in perceptions of present family relationships. The findings of this study raise questions about the general perception that individuals who grew up in alcoholic families experience more family dysfunction in adulthood. The presence of two factors together--family history and alcohol problems in the subject--produced the perception of family dysfunction. PMID- 2310858 TI - Alcohol education for 13 year olds--does it work? Results from a controlled evaluation. AB - This paper presents the findings from a controlled prospective study of the effectiveness of a school-based alcohol education package for 13 year olds. The research had three phases: (1) baseline survey of alcohol-related knowledge, attitudes and behaviour; (2) development and teaching of a short alcohol education package and (3) follow-up survey. The results indicate that the students who received the alcohol education knew more about alcohol than the controls. In addition, the educational intervention was found to have influenced the self-reported last consumption of alcohol and maximum consumption, with the 'educated' youngsters generally exhibiting more restrained behaviour. There has been little scientific evidence that past alcohol education has been effective in changing young people's drinking behaviour. The outcome of this research reinforces some recent studies which suggest the way forward may lie in an educational approach which takes account of social influences on substance use and misuse. PMID- 2310859 TI - 'Drug scene'--how will it be in the next century? PMID- 2310860 TI - The characteristics of alcoholics in treatment arrested for Driving While Impaired. AB - Relationships were explored between various characteristics and Driving While Impaired (DWI) arrests, within a sample of 258 hospitalized male alcoholics. Information on four groups of variables were collected using a self-administered questionnaire: socio-demographic characteristics, drinking characteristics, driving characteristics and psychosocial characteristics. Subjects were subdivided into three groups; those with zero DWI arrests, one DWI arrest and multiple DWI arrests. The results of bivariate analyses showed that while Groups 0 and 1 were very similar to each other, those in Group 2 differed significantly from at least one of the other two groups for about one half of the variables studied. A multivariate discriminant analyses demonstrated that there were no important differences between people with 0 and 1 DWI arrests, as people with one arrest were usually classified as having zero arrests. PMID- 2310861 TI - A comparison of the WAIS and WAIS-R in matched UK samples. AB - A matched samples design was employed to compare WAIS and WAIS-R IQ in UK subjects. The WAIS yielded significantly higher mean Full Scale, Verbal and Performance IQs. The mean differences were 7.5, 6.4 and 7.9 IQ points respectively. The WAIS and WAIS-R samples were broadly representative of the UK adult population in terms of age, sex and social class distribution, and therefore provide tentative estimates of population mean scores for both Wechsler scales. Mean WAIS IQ was 108.6, suggesting that the WAIS yields inflated IQ scores in the contemporary UK population. Encouragingly, mean WAIS-R Full Scale IQ was 101.1, suggesting that it neither markedly underestimates nor overestimates IQ in the UK. PMID- 2310862 TI - Identification of tachistoscopically presented alphanumeric stimuli in schizophrenia. AB - Schizophrenics, general medical patients and non-patient controls were compared for their ability to identify tachistoscopically presented alphanumeric stimuli at six exposure durations. Schizophrenics did not differ from general medical patients but both were inferior to controls - a difference that increased as the exposure duration decreased. PMID- 2310863 TI - Good and bad clinicians: supervisors' judgements of trainees' competence. AB - Experienced supervisors of trainee clinical psychologists used 24 scales to rate four concepts: 'your stereotype of a good trainee'; "a good trainee well known to you'; 'a bad trainee well known to you'; and 'your stereotype of a bad trainee'. Similar ratings were given for both the good trainee concepts, which were rated differently from both the bad concepts, which were also rated differently from each other. Factor analysis revealed that the supervisor's judgements fell across two interpretable dimensions. PMID- 2310864 TI - British community norms for the Brief Symptom Inventory. AB - British community norms (N = 376) for the Brief Symptom Inventory (Derogatis & Spencer, 1982) are presented. Means are significantly higher than previously published US norms for all symptom dimensions, and show variability according to age, sex and work status. The proportion of 'cases' in the sample is similar to other British estimates. It is recommended that culturally relevant norms should be established and used in future work with this instrument. PMID- 2310865 TI - Evaluation of a self-help manual for young offenders who drink: a pilot study. AB - Adolescent offenders have been identified as heavy drinkers, in some cases drinking being causally related to offending. Forty-five male young offenders who drink were selected from the population of a Young Offenders Centre. They were matched for age and self-reported alcohol consumption, then allocated to one of three conditions: no intervention; minimal intervention (given a behavioural self help manual to read alone); and group intervention (manual read aloud in groups). At 15-month follow-up, there were no significant differences in reconviction rates in the three conditions. Information useful in the design of future studies was gained, and recommendations are made. PMID- 2310866 TI - A classroom rating scale for use with mentally handicapped children: a replication of the ADIECAS. AB - The Attention/Distraction: Inhibition/Excitation Classroom Assessment Scale (Evans, 1975; Evans & Hogg, 1984) was administered to 80 children with severe learning difficulties with the Peabody Picture Vocabulary Test (PPVT) and subscales of the British Ability Scales (BAS). Factor analysis replicated the Attention/Distraction scale but the Inhibition/Excitation scale split into a verbal component and the remaining items. A new factor named responsivity to consequences was identified. Attention/Distraction showed good concurrent validity with the BAS and PPVT. This study shows the robustness of the Attention/Distraction: Inhibition/Excitation Classroom Assessment Scale as a measure of individual differences in children with severe learning difficulties. PMID- 2310867 TI - Correlations of session evaluations with treatment outcome. AB - Do evaluations of psychotherapy sessions predict treatment outcome? Clients (n = 40) and their therapists rated each session (n = 16 per client) of their brief therapy on the Session Evaluation Questionnaire (SEQ), which yields indices of session Depth (power, value) and Smoothness (comfort, safety). External raters rated tape-recordings of half of the sessions. SEQ ratings by one of two principal therapists were strongly correlated with client improvement on self report measures; those of the other therapist were not. Clients' SEQ ratings did not show the expected correlations with improvement. External raters' ratings of session Smoothness were significantly correlated with client improvement on some measures. PMID- 2310868 TI - Consideration of pigeon-holing and filtering as dysfunctional attention strategies in schizophrenia. AB - Difficulties in the use of both filtering and pigeon-holing strategies have been suggested as partial explanations for the information processing deficits typically noted with schizophrenic subjects. The study reported here examined the operation of both of these attentional strategies in a group of schizophrenic subjects and in a group of psychiatric control subjects. Subjects were asked to identify a target syllable in the presence of several levels of competing speech. A sensory filter could be profitably invoked when the target and the competing speech were presented to separate ears. Pigeon-holing was assumed to facilitate performance when both the target and the competition occurred in both ears. Results suggested that schizophrenic subjects are relatively efficient in using filtering strategies, but have more difficulty employing pigeon-holing strategies to allocate efficiently attentional resources. PMID- 2310869 TI - Guttman scaling in agoraphobia: cross-cultural replication and prediction of treatment response patterns. AB - The Fear and Avoidance Scales (FAS) is an 11-item questionnaire consisting of two subscales that measure features of agoraphobia and claustrophobia and that were demonstrated to be valid Guttman scales in a British clinical population. The purposes of the study reported here were to replicate the scale characteristics in the United States and to determine if improvement during treatment would follow the sequence predicted by the hierarchy implied in the scales. The FAS was given to 25 female agoraphobics before and after behavioural treatment. A principal components analysis replicated the agoraphobia and claustrophobia factors established in the British sample. Scalogram analyses showed that the Claustrophobia subscale of the FAS was a valid Guttman scale in the US sample whereas the Agoraphobia subscale yielded a high coefficient of reproducibility but a low coefficient of scalability. Treatment reduced the patients' fears and avoidances in the predicted sequence since for both scales the hierarchy of items remained unchanged following treatment. PMID- 2310870 TI - Relationships between happiness, behavioural status and dependency on others in elderly patients. AB - Feelings of dependency on others were measured, by different scales, in two different samples of elderly people: 33 acute in-patients and 25 attenders at a geriatric day hospital. Findings were similar in each location. Dependent attitudes increased with the duration of patients' previous in-patient experience, and correlated negatively with subjective well-being but not at all with behavioural status. These results are consistent with theories which attribute low morale to feelings of dependence and this, in turn, to the experience of residential care. They are inconsistent with the view that dependence on others is a positive feature of old age. In addition, patients' subjective well-being was completely unrelated to nurse ratings of their behavioural status, and subjective ratings by nurses correlated somewhat with patients' behavioural status but not at all with their subjective well-being. PMID- 2310871 TI - Situation-response (S-R) questions for identifying the function of problem behaviour: the example of thumb sucking. AB - The purpose of this study was to construct and validate the prototype of a structured interview or questionnaire for use in the functional assessment of problem behaviour. A set of situation-response (S-R) questions was used to test hypotheses concerning discriminative stimuli SD, inhibitive stimuli (SI) and the function of a problem behaviour (R). The situations in S-R questions include stimuli which are expected (a) to set the occasion for, or (b) to inhibit the problem behaviour. The response part includes the problem behaviour as well as behaviour patterns with known functions. The problem behaviour is correlated with those behaviour patterns whose functions it shares. For the study of 26 children suffering from orthodontal problems due to excessive thumb sucking, a structured interview was developed and validated for identifying (a) stimuli (SD) that trigger excessive thumb sucking (problem behaviour), (b) stimuli (SI) that inhibit this response, and (c) the function of thumb sucking. PMID- 2310872 TI - Children's drawings of an anxiety-eliciting topic: effects on the size of the drawing. AB - Our aim was to investigate whether or not children's drawings of a potentially threatening topic (a Hallowe'en witch) were made significantly smaller than drawings of a non-threatening topic (a woman). The first study confirmed an earlier claim by Craddick (1963) that drawings of a witch were made significantly smaller on the day before Hallowe'en compared to drawings made one week before or after, but we found that drawings of a non-threatening topic (a woman) changed in size in exactly the same way. Furthermore, we found no evidence that children became significantly more frightened of witches as Hallowe'en approached. In the second study, questionnaire responses were used to allocate children into two groups, those who were scared of witches and those who were not. Scared children drew both smaller witches and larger women than did non-scared children, with the result that relative heights of witches compared to women differed significantly between the two groups. However, only the difference in the height of the drawings of a woman was statistically significant. The implications of these results for the clinical assessment of children through their drawings are discussed. PMID- 2310873 TI - Estimation of verbal intelligence in an elderly community: a prediction analysis using a shortened NART. AB - Estimation of premorbid IQ is useful for estimating true cognitive decline in dementia. The National Adult Reading Test-NART (Nelson, 1982)-has been shown to estimate premorbid IQ in hospital patients. NART is potentially of use in epidemiological studies. However, asking community elderly people to read a list of irregular and difficult words can cause distress. This paper explores the possibility of administering only a part of the NART. On the basis of scores on the first half of the test from an elderly rural community sample (N = 316), a regression equation has been developed to predict performance on the second half of the test. It was built using the scores of half the population free from clinical diagnoses and tested on the other half. It was also applied to a demented group and a depressed group from the same population. Total NART scores predicted in this way were highly significantly correlated with the actual NART score for all groups. Recommendations about the use of this shortened test are made. PMID- 2310874 TI - Assessment of articulated thoughts in social anxiety: modification of the ATSS procedure. AB - In the present study an assessment strategy was developed which adapted the Articulated Thoughts during Simulated Situations (ATSS) paradigm devised by Davison, Robins & Johnson (1983). That strategy was applied to the assessment of social anxiety. Responses of 10 socially anxious and 10 non-anxious males were compared as they imagined themselves participating in videotaped simulations of heterosocial interactions. Each time the subject was aware of a reaction to the events depicted, he stopped the videotape, and then articulated his thoughts. Consistent with cognitive conceptualizations of social anxiety, the articulated thoughts of anxious males were distinguished by a greater focus upon the self in general and by a concentration upon irrational concerns in particular. In contrast, non-anxious males provided larger proportions of thoughts directed towards the environment and in particular, provided more positive thoughts both about other persons and their interactions in general. The theoretical and methodological implications of the data are discussed. PMID- 2310875 TI - Prediction of survival in dementia by cognitive tests: a six-year follow-up. AB - One hundred and sixteen elderly female in-patients with confirmed diagnoses of senile or arteriosclerotic dementia were tested on the Paired-Associate Learning Test (PALT) and Cognitive Assessment Scale (CAS) of CAPE and were followed up annually for six years. Comparison of those patients who had died by each follow up date with those who had survived showed that in general the latter had had better PALT and CAS scores. PMID- 2310876 TI - Cytogenetic follow-up after allogeneic bone-marrow transplantation for Ph1 positive chronic myelogenous leukemia. AB - Serial cytogenetic studies were carried out on 36 patients with Ph1-positive chronic myelogenous leukemia treated with allogeneic bone-marrow transplantation from unlike sex (21 patients) or like sex (15 patients) donors. Fourteen of the 21 sex-mismatched and 12 of the 15 sex-matched donor marrows were T cell depleted. Disease relapse was documented in 19 of the 26 patients who received T cell-depleted marrow, and in none of the 10 patients who received non-T cell depleted marrow. In the group of patients with unlike sex donor, a triple donor/normal recipient/Ph1-positive recipient or a double donor/Ph1-positive recipient chimerism was documented during the subsequent months, while on alpha interferon treatment for relapse. Two of these patients subsequently showed a complete disappearance of the Ph1 chromosome. Unstable and/or stable, clonal or non-clonal chromosome changes were detected in Ph1-positive cells from 12 of the 19 patients who relapsed. Analysis of the identified stable changes showed a non random distribution of breakpoints with clustering to chromosome nos. 1, 4, 7 and 12. PMID- 2310877 TI - Successful pregnancy following bone marrow transplantation for leukaemia. AB - We report three pregnancies with successful outcomes in two women following allogeneic bone marrow transplantation (BMT) for acute leukaemia using high dose melphalan alone as conditioning therapy. The increasing application and success of BMT together with the instigation of conditioning regimens that do not include total body irradiation should increase such cases. These and previous cases document that a normal outcome of pregnancy is likely in these patients. PMID- 2310878 TI - Evaluation of cytoreductive therapy prior to high dose treatment with autologous bone marrow transplantation in relapsed and refractory Hodgkin's disease. AB - Based on observations that bulky disease at autologous bone marrow transplantation (ABMT) may be correlated with poor outcome in Hodgkin's disease, we have assessed the ability of conventional-dose chemoradiotherapy to reduce tumour burden to a minimum prior to ABMT. Thirty-seven patients with relapsed or refractory Hodgkin's disease referred for intensive therapy and ABMT were treated initially with one to five cycles of DHAP chemotherapy. All patients had previously received MOPP and ABVD chemotherapy or similar regimens. Four patients achieved complete remission (CR) and 12 partial remission (PR), for a total response rate of 43%. Eight partial responders and four non-responders to DHAP achieved significant further tumour reduction with local radiotherapy (five CR, seven PR). Six of 10 non-responders to DHAP responded to alternative salvage chemotherapy (mini-BEAM, CEP or augmented CVP). Overall, 24/37 patients (65%) achieved effective cytoreduction (nine CR, 15 PR with minimal disease) and have proceeded to ABMT. Patients with bulky disease at relapse or limited stage (II, IIIA) at diagnosis were less likely to respond to DHAP, but some of these could be cytoreduced with alternative therapy. In addition, the number of prior chemotherapy regimens correlated inversely with likelihood of response to DHAP. The results indicate that approximately two-thirds of patients with Hodgkin's disease who relapse after MOPP and ABVD-like regimens can achieve effective cytoreduction with conventional-dose chemoradiotherapy and proceed to ABMT in CR or PR with minimal disease. PMID- 2310879 TI - The changing face of public health. PMID- 2310880 TI - More incentives needed for doctor managers. PMID- 2310881 TI - Anaesthetic management of delivery in a morbidly obese patient. PMID- 2310882 TI - Hyperosmolar non-ketotic diabetic decompensation. PMID- 2310883 TI - Psychiatric benefits of physical exercise. PMID- 2310884 TI - Psychogenic regional pain. AB - Psychogenic regional pain develops in association with emotional stress. This article suggests that the role of the liaison psychiatrist is to encourage other clinicians to evaluate emotional factors, restrict excessive investigation and provide appropriate reassurance and treatment for such problems. PMID- 2310885 TI - How to perform a muscle biopsy. AB - Muscle biopsy can easily be performed as a needle procedure by an experienced clinician. Two complementary needle techniques are now available. Ultrasound imaging of the muscle is a valuable precursor to ensure diseased tissue is obtained. Orientation of the muscle sample and processing by appropriate histochemical techniques are crucial. PMID- 2310886 TI - 'Grown-up' survivors of congenital heart disease: who knows? Who cares? AB - 'Grown-up' congenital cardiac patients are an increasing medical community, not at present being properly cared for in any country. Information on over 2000 patients aged 15-65 years with congenital heart disease who have been treated in the National Heart Hospital provides the data for this report. PMID- 2310887 TI - Management of the pregnant opiate user. AB - Increasing numbers of women are seeking help for drug misuse. In addition to problems associated with drug dependence, there are also problems concerning child care, pregnancy and women's health. In this paper we discuss the management of the pregnant opiate user, effects of opiate use in utero and postpartum and ways in which non-drug services can assist in the early identification and treatment of these women. PMID- 2310888 TI - Interhospital transfer of the critically ill patient by helicopter. AB - The transfer of critically ill patients between hospitals is difficult for staff and dangerous for patients. A dedicated helicopter transfer scheme has been designed to deal with these problems. PMID- 2310889 TI - Low-grade endometrial stromal sarcoma treated with a progestogen. PMID- 2310890 TI - Higher training for intensive care. PMID- 2310891 TI - Biomechanical and histomorphological changes in expanded rabbit skin. AB - In 12 rabbits, biomechanical and histomorphological properties were determined in expanded, sham-operated and non-operated control skin. Results were evaluated in paired fashion. Both expanded and sham-operated skin showed a significant loss of stiffness of 60% and 35% respectively (rho less than 0.001 and rho less than 0.05). In addition, maximum stiffness in expanded skin was reached at a shorter extensibility than in sham-operated or non-operated control skin. Histomorphological examination revealed thickened dermal collagen bundles with loosened packing of collagen fibrils in both expanded and sham-operated skin. It is concluded that the surgical procedure of balloon implantation is responsible for a significant part of the reported biomechanical and histomorphological findings. Wound healing, in addition to the delay phenomenon, may therefore be a mechanism involved in skin expansion. PMID- 2310892 TI - Super-specialization leads to higher surgical standards? PMID- 2310893 TI - A new operative technique for congenital gigantism of the toes. AB - A technique for reducing congenital gigantism of the toes which has been used successfully in four patients is described. PMID- 2310894 TI - Intractable digital neuroma pain; the ultimate solution? AB - A case is presented in which, following the failure of several surgical and non surgical procedures to control the increasingly severe pain in an amputation thumb stump, a toe transfer was carried out, successfully relieving the symptoms without transfer of the pain to the donor site. The patient has remained pain free for 3 years. PMID- 2310895 TI - The second dorsal metacarpal artery neurovascular island flap. AB - The clinical applications of the second dorsal metacarpal artery island flap are illustrated by selective case reports from a series of 12 consecutive cases carried out in this Unit. In five cases the flap was transferred as a neurovascular island flap for sensory resurfacing of the thumb. There were no failures and no donor site complications. The anatomy and clinical dissection of the flap are described. PMID- 2310896 TI - The distally-based dorsal hand flap. AB - The planning and clinical applications of a series of reverse dorsal hand flaps are described. This new flap is based on a direct cutaneous branch of the dorsal metacarpal artery. It is particularly useful in resurfacing web spaces as well as dorsal metacarpal and phalangeal skin defects. The behaviour of 21 such flaps, all raised in the form of an island, was that of a conventional axial pattern flap. PMID- 2310897 TI - The use of semi-permeable membranes for wound management. AB - This paper reports a study comparing bags made from expanded polytetrafluoroethylene semi-permeable membranes and standard plastic bags to treat burns of the hands. There was much less maceration in the PTFE bag, which allowed easier assessment of the extent and depth of burn, and only one daily dressing change was needed. The two types of bag were similar with regard to ease of use, low bacterial contamination and allowing good mobilisation of the hand. Ease of use has meant that a greater number of patients with superficial burns can be treated as outpatients and many are able to do their own daily dressing change, so fewer attendances at the clinic are needed. PMID- 2310898 TI - On the nature of keloid and hypertrophic scars. AB - Clinical observations make it possible in most cases to differentiate between keloid and hypertrophic scars. This suggests that different biological factors are involved in the two groups. In clinical practice in the United Kingdom most keloid scars occur spontaneously. In black-skinned people and orientals the factors of keloid and hypertrophic scars may overlap and potentiate each other. PMID- 2310899 TI - A new system of treating wounds by a continuous topical application of medication. AB - A new procedure using a silicone gel sheet that enables the continuous topical application of a drug to a wound, and the effect of this therapeutic procedure on experimental skin flaps of rats, are described. Although a silicone gel sheet without a drug did not augment the flap survival length, silicone gel sheets containing Prostaglandin E1 (PGE1) and Ofloxacin showed significant elongation of the survival length of the flaps without signs of infection. Similarly, silicone gel sheets containing PGE1 inserted under the flap, like a drain, also showed statistically significant augmentation of the flap survival length. These facts showed a therapeutic potential of this new silicone gel sheet containing a drug. PMID- 2310900 TI - Web neck deformity; anatomical considerations and options in surgical management. AB - Web neck deformity has been recognised for over 100 years and during that time there has been a large amount of literature devoted to it. There has been surprisingly little information published on the exact nature of the deformity, particularly the exact site and composition of the web and the presence or absence of any other soft tissue anomalies in the head and neck, which could modify a surgical approach. Our paper will describe the "simple" webbing found in four cases of Turner's syndrome and one case of Klippel-Feil syndrome, and discuss some of the associated features seen in these syndromes. We also review the major methods of surgical treatment and examine the role of tissue expanders in the surgical correction of this anomaly. PMID- 2310901 TI - Magnetic resonance imaging of the normal prostate at 1.5 T. AB - Prostatic magnetic resonance images of 22 male volunteers less than 30 years old and with no known genito-urinary tract disease were obtained at 1.5 T. Normal anatomical features of the prostate were studied with spin-echo techniques. Different zones of the normal gland are shown by T2-weighted images: the anterior fibromuscular fascia, the central prostate, the peripheral prostate and the periurethral zone can be differentiated. The normal prostate gland is shown on T1 weighted images as a homogeneous appearance. It is important to recognize the normal zonal anatomy of the prostate since prostatic disorders arise in different anatomical zones. PMID- 2310902 TI - Nasopharyngeal carcinoma: the significance of neck node involvement in relation to the pattern of distant failure. AB - The pattern of distant failure of 759 Stage I-IV cases of nasopharyngeal carcinoma was studied. The most common sites of distant metastasis were, in descending order, bone, lung and liver. The N stage, T stage and the characteristics (size and degree of fixation) of the neck nodes involved were found to be significant prognostic factors determining the development of distant metastasis. The bilaterality of neck node involvement, sex, age, haemoglobin and white blood count at diagnosis were not significant. The discriminating effect of N stage holds true in patient groups stratified for the node size and degree of fixation. The superiority of the Ho stage classification was confirmed. The high incidence of distant failure in patients with T3, N3, or bulky or fixed neck node involvement warrants further clinical trials to explore the role of adjuvant chemotherapy. PMID- 2310903 TI - Radiobiological rationale for compensation for gaps in radiotherapy regimens by post-gap acceleration of fractionation. AB - It is now recognized that clonogenic tumour cells may repopulate vigorously during radiotherapy. Gaps in treatment schedules which lead to prolongation of overall treatment time may therefore cause sparing of tumour. Acute-responding normal tissues will also be spared if repopulation by surviving stem cells takes place. However, it is unlikely that stem cells in late-responding normal tissues repopulate significantly over the time-scale of a conventional treatment regime; these tissues will therefore experience little or no sparing as a result of a gap. This poses a dilemma since tumour cell repopulation implies that an increased therapeutic effect in the post-gap phase of treatment may be necessary to compensate for any prolongation of treatment time, but it is difficult to achieve increased tumour effect without also increasing damage to late-responding normal tissues. Neither increased total dose nor increased fraction size is able to achieve this. A possible solution is provided if total treatment time can be held constant, with unchanged total dose and fraction size, by use of twice-daily conventionally sized dose fractions administered after the gap. Provided the twice-daily fractions are sufficiently spaced (not less than 6-8 h apart), the result will be to offset repopulation in tumour and acute-responding normal tissues without additional impairment of late-responding normal tissues. The feasibility of the approach depends on being able to complete treatment by the time originally intended; it is therefore more readily applicable to gaps occurring early rather than late in a treatment schedule. The strategy should be especially advantageous for tumours with rapid repopulative potential in sites where risk of damage to late-responding normal tissues imposes limitation of dose. PMID- 2310904 TI - An assessment of the sensitivity of in vivo 31P nuclear magnetic resonance spectroscopy as a means of detecting pH heterogeneity in tumours: a simulation study. AB - The presence of hypoxia and low pH in tumours is known to influence several treatment modalities including radiotherapy, chemotherapy and hyperthermia. Hypoxic and acidic regions have been demonstrated in tumours using pH and pO2 microelectrodes. The technique has shown marked heterogeneity within individual tumours. A non-invasive measure of intracellular pH is provided by 31P nuclear magnetic resonance (NMR) spectroscopy from determination of the chemical shift of inorganic phosphate, and is being increasingly applied to the study of human tumours in vivo. Based upon the assumption that hypoxic cells are also acidic, we have assessed the ability of a whole-body NMR spectrometer to detect acidic subpopulations within a tumour using simulated tumour spectra. In these simulations the size of the acidic subpopulation, assigned pH values from 5.0 to 7.0, was varied between 5% and 50% of the neutral "control" population. Gaussian noise was added to the simulated spectra giving signal-to-noise ratios for the neutral control inorganic phosphate peak of 3, 5 and 7, which are typical of values encountered in human tumour measurements. From the results of the simulations it seems unlikely that human hypoxic, and presumably acidic, cell fractions, typically 1-15%, will be detected by this method in the presence of signal-to-noise levels characteristic of current equipment. Therefore, whole-body in vivo 31P NMR spectroscopy may fail to identify significant pH heterogeneity within human tumours. Improvements in signal-to-noise and line separation owing to improvements in technique and higher field strength instruments may improve sensitivity to heterogeneous populations. PMID- 2310905 TI - Further comparisons of films, screens and cassettes for mammography. PMID- 2310906 TI - Pelvic actinomycosis: beware the intrauterine contraceptive device. PMID- 2310907 TI - Unusual appearances of an adrenal mass on computed tomography. PMID- 2310908 TI - Magnetic resonance imaging of the chest in infectious mononucleosis. PMID- 2310909 TI - Case of the month. Digging for a diagnosis. Gardner's syndrome complicated by a periampullary carcinoma. PMID- 2310910 TI - Cineradiography of a cracking joint. PMID- 2310911 TI - A critical appraisal of coagulation studies prior to transfemoral angiography. PMID- 2310912 TI - Effect dose equivalent in dual X-ray absorptiometry. PMID- 2310913 TI - Changes in relative biological effectiveness with depth of neutron beams. PMID- 2310914 TI - Screening for breast cancer. PMID- 2310915 TI - Vasopressin release in response to intravenously injected contrast media. AB - We have previously reported that intravenously administered contrast media produce a rise in plasma vasopressin (antidiuretic hormone) concentrations. We have now shown that this occurs both when contrast medium is injected into a peripheral vein and when it is centrally injected into the right atrium. The peak vasopressin concentration recorded varies with the osmolality of the contrast medium. The vasopressin response was greater when contrast agent was centrally injected. PMID- 2310916 TI - The incidence of post-operative urinary tract infection in patients with ureteric stents. AB - Despite the many advantages provided by the ureteric stent, it produces a foreign body reaction and increases the risk of infection. We undertook a study on the rate of infection in a group of paediatric patients with ureteric stents; 40 ureteric stents, 6 to 9 F, were used in 36 children undergoing the following procedures: 18 pyeloplasties, 20 antireflux ureteric reimplantation and 2 uretero rectal anastomoses. Only patients with sterile urine pre-operatively were included in the study. All received antibiotic cover in the post-operative period. Positive urine cultures were found in only 3 patients (7.5%). In spite of this low incidence, the urine specimens collected from all children 1 month after removal of the stent showed a much higher incidence of infection. It was concluded that ureteric stenting is a safe procedure with a low rate of infection provided that antibiotic cover is given. PMID- 2310917 TI - Parameatal urethral cysts of the glans penis. AB - Parameatal urethral cysts are uncommon in the male. We have seen 9 cases and have reviewed these and the 35 cases reported in Japan between 1919 and 1984. The cysts recurred after rupture or aspiration in 3 cases and complete excision is recommended. PMID- 2310918 TI - Wegener's granulomatosis presenting as granulomatous prostatitis causing urinary retention. PMID- 2310919 TI - Metastatic renal carcinoma mimicking carotid artery aneurysm. PMID- 2310920 TI - Hamartoma of the urinary bladder in an infant with Beckwith-Wiedemann syndrome. PMID- 2310921 TI - Venous infarction of the testis secondary to acute epididymitis. PMID- 2310922 TI - Wegener's granulomatosis in the bladder. PMID- 2310923 TI - "The disappearing catheter"--a complication of intermittent self-catheterisation. PMID- 2310924 TI - Alternative techniques for scrotal reconstruction. PMID- 2310925 TI - Inverted papilloma of the ureter with malignant change. AB - Three patients with inverted papilloma of the ureter are described. A range of histological features was seen, including one showing malignant change. This condition, which is probably more common than previously thought, can be successfully treated by conservative surgery and close follow-up. PMID- 2310926 TI - Acceleration of flow rate as a screening test for detrusor instability in women with stress incontinence. AB - Forty females with urinary stress incontinence (mean age 52 +/- 10 years) and 20 age-matched controls (mean age 49 +/- 15 years) underwent complete urodynamic evaluation. In the former group, all patients complained of irritative bladder symptoms (frequency, nocturia, urgency) and 20 of them (Group B) showed detrusor instability (DI); in the other 20 (Group A) a final urodynamic diagnosis of genuine stress incontinence (GSI) was made. Instability was not apparent in Group B at standard filling cystometry, but had to be elicited through aggressively stressing the bladder by provocation tests. In all women the acceleration of flow rate (a, in ml/s2) was calculated from free flow uroflowmetry as the ratio of peak flow divided by the time to peak flow. This parameter did not differ significantly in GSI patients when compared with controls but proved higher in the DI group than in either the controls or the GSI patients. It was concluded that measuring the acceleration of flow rate is a simple and reliable test which improves the accuracy of diagnosis of detrusor instability in stress incontinent women. PMID- 2310927 TI - Clean intermittent self-catheterisation in 172 adults. AB - We report the results of clean intermittent self-catheterisation (CISC) in 172 adults (68 male, 104 female). Seven patients were unable or unwilling to master the technique and 145 still remain on CISC, representing a total experience of 6981 patient-months. Ten patients required readmission: 5 for retraining and 5 for complications (average hospital stay 2.4 days); 123/163 patients catheterised themselves every 3 to 4 h and 92 were continent on CISC; of the 107 patients incontinent prior to starting CISC, 101 were improved; 70 patients had no infections whilst on CISC, the mean infection rate being 1 per 14 patient-months; 29% of patients experienced persistent urethral bleeding; 156/163 patients were satisfied or very satisfied with CISC and 140 found the technique easy or very easy; 76 patients had never visited their GP for a urinary problem whilst using CISC and the mean rate was 1 visit per 8 patient-months. CISC is an easily learnt technique that is safe and acceptable to patients, and one which places few extra burdens on hospital or community resources. PMID- 2310928 TI - Neodymium-YAG laser irradiation of stage T2 muscle-invasive bladder cancer. Long term results. AB - The study group consisted of 15 patients with solitary stage T2 bladder tumours treated with transurethral resection (TUR) and subsequent neodymium-YAG laser irradiation. Ten patients are alive without evidence of cancer 56 to 78 months (mean 67) after treatment; 1 died of cardiovascular disease 2 years after treatment and autopsy revealed no cancer. In 4 patients the treatment failed and cystectomy or external beam radiation was carried out. The long-term results indicate the combination of TUR and laser irradiation to be beneficial in the management of T2 tumours in selected cases. PMID- 2310929 TI - Estimation of growth fraction in situ in human bladder cancer with bromodeoxyuridine labelling. AB - A group of 8 patients with invasive bladder cancer received fractionated intra arterial infusions of the thymidine analogue bromodeoxyuridine (BrdU), 150 mg, every 6 to 10 h for 3 days before endoscopic cold cup biopsy to label tumour cells in the proliferative pool (growth fraction). The tumour specimens were fixed and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody. There was an area which could not be stained with anti-BrdU monoclonal antibody surrounding the stained area where diffusion effects could be excluded. This indicates a growth fraction less than 1 and implies that a proportion of the tumour cells in bladder tumours are cycling and contributing to growth. The BrdU labelling index (growth fraction) was determined by counting the number of BrdU labelled cells in the well labelled tissue sections. The average growth fraction of invasive bladder cancer was 38.4 +/- 7.7% (range 26.9-48.1%). Grade 3 tumours averaged 42.8 +/- 5.4% labelling versus 31.0 +/- 4.4% in grade 2. The higher growth fraction may indicate greater biological malignancy. These results indicate that immunohistochemical studies of cell kinetics using BrdU monoclonal antibodies may provide information about the biological characteristics of bladder tumours in situ. PMID- 2310931 TI - Significance of histological prognostic indicators in patients with carcinoma of the prostate. AB - The relationship between histological prognostic indicators and their relative significance in prognosis were studied in 139 patients who underwent radical prostatectomy. The estimated progression rates at 5 and 8 years were 14 and 52% respectively for patients with high grade tumours, 25 and 50% for those with capsular penetration, 31 and 58% for patients with seminal vesicle invasion and 23 and 55% for those with lymph node metastases. Each of the 4 parameters yielded an approximately equal increased risk of disease progression at 5 and 8 years. The occurrence of 2 or more risk factors in the same patient did not result in a statistically increased risk of progression at 5 and 8 years. The effect of capsular involvement on progression was directly related to the extent of invasion. The progression rate at 8 years was 3% for patients with mild involvement, 19% for those with extensive invasion and 50% for those with capsular penetration. PMID- 2310930 TI - Long-term follow-up of intravesical Epodyl therapy for superficial bladder cancer. AB - The records of 111 patients with multiple superficial grade 1-2 transitional cell tumours of the bladder treated with intravesical Epodyl and followed up for a mean period of 6.4 years were retrospectively analysed. The study showed that 65% of patients responded completely after 12 weekly instillations and 46% of these remained continuously free of disease for 5 years. An initial complete response to therapy and lower pathological grade seemed to indicate a long-term successful response to treatment. In patients who failed to respond by 1 year, further therapy was of no benefit. Clearance of bladder disease by 1 year carried a 14% risk of subsequent tumour invasion by 5 years. This risk increased to 75% in those who failed to respond by 1 year. PMID- 2310932 TI - Complete urethral stricture of the membranous urethra: a different perspective. AB - Seven patients with complete rupture of the membranous urethra secondary to trauma were treated by internal optical urethrotomy (OU). All underwent initial suprapubic catheter drainage. The diagnosis of complete urethral rupture was confirmed by ascending and descending urethrograms and subsequent urethroscopy. OU was performed 3 weeks to 8 years following injury. Although all patients required further OUs for recurrent strictures, all can pass urine satisfactorily. Two patients have slight stress incontinence. This technique is a viable alternative to more conventional procedures for this condition. PMID- 2310933 TI - Comparison of catheter surface morphologies. AB - The surface morphologies of different generic types of Foley catheter have been investigated using scanning electron microscopy (SEM). The characteristic features of each material are illustrated and it is shown that distinct differences exist between the inner and outer surfaces of latex-based catheters; these differences are attributed to the methods of manufacture. The possible relations between morphology and performance in situ are discussed. PMID- 2310934 TI - Prostaglandin E1 in erectile dysfunction. Efficiency and incidence of priapism. AB - Prostaglandin E1 (PGE1) was used for diagnostic and therapeutic purposes in 149 men with erectile dysfunction over a period of 20 months (February 1987-October 1988). The intracavernous application of PGE1 in varying doses resulted in an erection sufficient for sexual intercourse in 79% of cases. In order to differentiate between vascular and non-vascular impotence, 5 micrograms PGE1 were found to be a sufficiently high and safe dose for the first intracavernous injection. Local discomfort, ranging from mild to severe pain after injection, was recorded in 40% of patients. A significant difference in severe side effects was found between arterial, venous and non-vasculogenic impotence, the highest incidence of local pain occurring in non-vasculogenic patients. The most striking result was the occurrence of 4 cases of priapism, all in the non-vascular group, 1 of these occurring after the injection of only 5 micrograms PGE1. PMID- 2310935 TI - Abstracts of the proceedings of the Urological Society of Australia, 42nd annual scientific meeting. Melbourne, Australia, 2 to 7 March 1989. PMID- 2310936 TI - Buried penis. A novel approach. AB - Buried penis is a congenital abnormality in which the phallus is concealed within the subcutaneous tissue. The corporal bodies and glans have developed normally. A deficiency of penile shaft skin in association with abnormal mobility of the skin gives rise to the phenotypic appearance. The skin defect may be related to an abnormal attachment of dartos muscle during embryogenesis. Correction of this condition requires separation of these abnormal muscular attachments and provision of skin coverage of the penile shaft. It is imperative not to circumcise the patient as this will worsen the skin deficiency. We describe a novel technique for correcting buried penis performed on 12 patients at the Great Ormond Street Hospital for Sick Children. A satisfactory cosmetic result was obtained in all patients. PMID- 2310937 TI - Cardiorespiratory responses to stimulation of the nucleus reticularis gigantocellularis. AB - The nucleus reticularis gigantocellularis (NGC) has been shown to be involved in somatosensory and somatomotor functions. The purpose of the present study was to determine, in anesthetized cats, the modulatory influence of the portion of the NGC at the ponto-medullary border on respiratory and cardiovascular control. Electrical stimulation (25-100 microA 70 Hz, and 1.0-msec pulse duration) significantly depressed mean arterial pressure, heart rate, breathing frequency, tidal volume and phrenic amplitude. Chemical stimulation of NGC cell bodies (1.0 M L-glutamate or 10(-3) M kainic acid) elicited similar decreases in ventilation, arterial pressure and heart rate. These results show that selective activation of cell bodies in the ponto-medullary NGC can depress, in parallel, respiratory and cardiovascular activity and suggests that the influence of diverse sensory information within this region of the reticular formation must be inhibitory to respiratory and cardiovascular output. PMID- 2310938 TI - The effect of nimodipine on picrotoxin-induced seizures. AB - The effects of the calcium channel antagonist, nimodipine, on picrotoxin-induced myoclonic (MYO) and generalized tonic-clonic (GTC) seizures were investigated in male and female rats. In males, a dose-response study of nimodipine's effects on seizures induced by different doses of picrotoxin was conducted. In a second experiment, female rats were tested for latency to and incidence of MYO and GTC seizures after being pretreated with nimodipine 2 hr, 24 hr, or 72 hr prior to seizure testing. The results showed that, in males, various doses of nimodipine significantly increased the mean latencies to MYO and GTC seizures and significantly reduced the incidence of GTC seizures. In females, nimodipine significantly reduced the incidence and/or increased the latency of GTC seizures when given 24 hr of 72 hr prior to administration. In addition to the anticonvulsant effects, nimodopine significantly increased survival after seizures in both males and females even when it had no significant effects on seizure incidence or latency. The results of this study support the hypothesis of calcium involvement in seizure induction. However, the sex- and time-dependent nature of the nimodipine effects as well as the effects of nimodipine on survival after seizures suggest that the relationship between calcium and seizure activity is complex. PMID- 2310939 TI - A double-labeling method for AChE and fluorescent retrograde tracers. AB - Staining for the degradative enzyme acetylcholinesterase (AChE) is an important tool in studying central cholinergic/cholinoceptive systems. AChE staining has also been useful in identifying the projections of AChE-containing neurons and codistribution of AChE with other neurotransmitters. The intensity and opacity of conventional AChE histochemical reaction products, however, pose problems for such double-labeling studies. Here, we have successfully combined a modified version (37) of the Koelle-Friedenwald AChE reaction with retrograde transport of the fluorescent tracer, Fluoro-Gold (FG). By omitting the final intensification steps of the Koelle-Friedenwald reaction, a translucent, light-stable reaction product is created. Viewed under darkfield illumination, this precipitate is of similar intensity and sensitivity to that produced by conventional AChE histochemical processing. Prior administration of an AChE-inhibitor yields preferential staining of AChE-positive neuronal somata. This nonintensified darkfield AChE (NIDA) histochemical method was compatible with visualization of retrogradely transported FG in AChE-positive neurons, allowing unambiguous identification of the projections of AChE-containing neurons. PMID- 2310940 TI - Kinetic and inactivation studies of recombinant Drosophila choline acetyltransferase. AB - A cDNA for Drosophila choline acetyltransferase (ChAT) was expressed in E. coli and the recombinant enzyme partially purified. Kinetic analysis yielded the following constants for the recombinant enzyme; KmAcCoA = 29 microM, KmCoA = 25 microM, Kmcholine = 330 microM, and Kmacetylcholine = 2 mM. The recombinant Drosophila enzyme, like the enzyme from other species, exhibited an increase in activity as a function of increased salt concentration. Chemical modification studies using dithio-bis-nitro-2-carboxylate, butanedione, and diethylpyrocarbonate showed that the recombinant enzyme contains active site cysteine, arginine, and histidine residues. These studies demonstrate that the recombinant Drosophila ChAT possesses the same catalytic properties as the enzyme from a variety of other sources. PMID- 2310941 TI - Oxidative metabolism of the rat soleus neuron pool following hypobaric hypoxia. AB - After 7 weeks of hypoxic acclimation, oxidative enzyme (succinate dehydrogenase) activity of motoneurons in the rat soleus neuron pool was examined. Although the total oxidative metabolism of the neuron pool was not changed, the oxidative enzyme activity of small to medium sized (25-45 microns average soma diameter) alpha motoneurons was increased. These results indicate that hypoxia preferentially enhances the oxidative capacity of specific motoneurons in the neuron pool. PMID- 2310942 TI - Tyrosine pretreatment reverses hypothermia-induced behavioral depression. AB - Cold exposure accelerates the firing frequency of norepinephrine (NE) neurons, enhancing NE release and leading to NE depletion in specific regions of the brain. The accelerated firing activates the enzyme tyrosine-hydroxylase, making it more tyrosine sensitive. The reduction of brain NE is accompanied by a behavioral depression on the open field test. Two experiments were performed on adult male rats. First, it was determined whether systematic lowering of core body temperature produced behavioral depression in the swim test. Second, treatment with the NE precursor tyrosine was employed in an attempt to prevent hypothermia-induced behavioral depression. In Experiment 1, two levels of hypothermia were highly effective in producing behavioral depression in rats forced to swim in a narrow cylinder. In Experiment 2, treatment with tyrosine (400 mg/kg, IP) thirty minutes prior to the hypothermia procedure completely reversed the behavioral depression found in Experiment 1. Tyrosine administration did not significantly influence the rate of deep body cooling during the hypothermia treatment. PMID- 2310943 TI - Ipsapirone and 1-(2-pyrimidinyl)-piperazine increase rat locus coeruleus noradrenergic activity. AB - The effects of systemically administered ipsapirone, an aryl-piperazine compound, and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP), on locus coeruleus (LC) noradrenergic activity was investigated. On an equimolar basis both ipsapirone and 1-PP were approximately equipotent in increasing LC neuronal activity. However, pretreatment with 1-PP caused a significantly greater parallel shift to the right of the dose response curve for the inhibitory action of the LC alpha 2-receptor agonist clonidine compared to ipsapirone. Biochemically, pretreatment with SKF 525A, a compound which prevents the formation of 1-PP from ipsapirone, diminished the ipsapirone-induced increase in MOPEG-SO4 levels in the brainstem and cortex. These data, together with the findings that 1-PP is more potent than ipsapirone in displacing 3H-clonidine from cerebral cortical membranes, suggest that the parent drug influences LC neuronal activity via the action of I-PP on LC alpha 2-adrenoceptors. PMID- 2310944 TI - Local as well as remote functional and metabolic changes after focal ischemia in cats. AB - Behavior and limb placing ability were analyzed acutely and subacutely (up to 21 days) following unilateral occlusion of the middle cerebral artery (MCA) in cats. Immediately following occlusion, all tested cats started to display a sequence of different behaviors, characteristic for 1) an ipsilateral inhibition of dopaminergic activity in the caudate nucleus (CN); 2) an inhibition of GABAergic activity in the reticular substantia nigra (SNR); 3) a stimulation of GABA receptors in the deeper layers of the colliculus superior (CSDL) (starting-time of these phases: about 4, 12 and 25 min, respectively). The latter behavior was also present subacutely. In addition, unilateral orofacial dyskinetic movements were observed acutely as well as subacutely. Contralateral limb placing was deficient in all cats 60 min postocclusion; it was at least partly restored subacutely. Twenty-one days after the occlusion, [14C]-2-D-deoxyglucose uptake was relatively reduced in the ipsilateral CN (especially in its posterior part), the ipsilateral SNR and the ipsilateral CSDL. The anterior CN appeared to be less affected than the posterior CN. Metabolism was relatively reduced in the sensorimotor cortex only in part of the tested cats. The data show that unilateral MCA occlusion produces consistent functional changes in all structures studied apart from the sensorimotor cortex, viz. the CN, the SNR and the CSDL. PMID- 2310945 TI - Distribution of parvalbumin immunoreactivity in the rat septal area. AB - The distribution of parvalbumin (PV)-containing neurons and processes in the septal area of the rat brain was studied using a monoclonal antibody and the avidin-biotin immunoperoxidase method. PV-immunoreactive neurons were mainly located in the medial septum/diagonal band complex and in the horizontal limb of the diagonal band of Broca, showing a high density of heavily immunostained neurons and fibers. Nonimmunoreactive cells surrounded by PV-positive cells and processes were observed in the same region, but no pericellular basket-like arrangements were found. On the contrary, the dorsal, intermediate, and ventral nuclei of the lateral septum were practically devoid of PV-positive neurons and processes. Thus, in these nuclei only a very low density of isolated neurons was labeled; these were specially scattered in the ventrolateral septal nucleus and in the dorsolateral septal nucleus just below the corpus callosum. Delicate PV positive axonal plexuses were also observed in the dorsal and intermediate nuclei of the lateral septum. The immunopositive neurons displayed very different sizes and morphologies among the various septal nuclei and inside each of them, indicating that they do not belong to a single morphological class of neurons. Finally, the distribution of PV in the rat septal area is not directly related to cholinergic and GABAergic septal neurons. PMID- 2310946 TI - Search after neurobiological profile of individual-specific features of Wistar rats. AB - The first part of this study demonstrates that the bimodal shape of variation in "fleeing" and "nonfleeing" or "freezing" rats of an outbred strain of Wistar rats forms part of an overall biomodal variation in behavioural responses to injections of agents, which selectively alter, or reflect, the noradrenergic or dopaminergic activity in the ventral striatum, and dopaminergic activity in the dorsal striatum, the GABA-ergic activity in the substantia nigra, pars reticulata, and the GABA-ergic activity in the deeper layers of the superior colliculus. It is concluded that the "fleeing" and "nonfleeing" rats, each of them marked by their own trans-situational consistency in pharmacological and behavioural responses, represent the two fundamentally different types of individuals which normally exist in unselected populations of rodents. The second part of this study demonstrates that the pharmacogenetic selection of apomorphine susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) rats, i.e., one individual-specific feature of the overall bimodal variation for pharmacological responses in our outbred strain of rats, is a valid tool to disperse the above mentioned individual-specific features as far as possible. First, these lines allowed us to prove that the overall bimodal shape of variation in pharmacological and behavioral responses of individual outbred rats is in part genetically determined. Second, these lines allowed us to prove that a bimodal variation in neurochemical features of the circuitry, in which the ventral striatum is embedded, underlies the overall bimodal variation in pharmacological and behavioural responses. Third, these lines allowed us to demonstrate that a fundamental difference in organizing behaviour with the help of external and internal information has to be considered as a common factor giving rise to the individual differentiation found in the present study. Given the notion that this individual differentiation appears to be valid across lines, substrains and strains of rats, the present study lays the foundation for understanding at least a part of the physiological basis underlying differences between the two fundamentally different types of individuals existing in normal populations of rodents. PMID- 2310947 TI - Gender difference in susceptibility to picrotoxin-induced seizures is seizure- and stimulation-dependent. AB - In a dose-response study, the pattern of sex-associated susceptibility to picrotoxin-induced myoclonic, focal, akinetic, and generalized tonic-clonic (GTC) seizures was investigated in rats to determine whether the reported heightened susceptibility of females to seizures was a general phenomenon in rats or whether it was limited to specific types of seizures. The latency to and incidence of specifically categorized seizures were used as indices of susceptibility after male and female rats had been injected with picrotoxin (3-10 mg/kg). The results revealed that at low doses of picrotoxin (4 mg/kg), female rats had significantly shorter latencies to myoclonic seizures and significantly shorter latencies and higher incidences of GTC seizures. At higher doses of picrotoxin (8 and 10 mg/kg), the pattern of relative susceptibility of males and females to myoclonic seizures was reversed, with males having shorter latencies than females. There were no significant sex differences in the incidence of or latency to focal or akinetic seizures at any of the doses tested. These findings indicate 1) that there are significant sex differences in seizure susceptibility only for specific seizure categories in rats; and 2) that for seizure categories where significant sex differences were identified, the observed pattern of relative susceptibility of males and females depends on the dose of picrotoxin tested. Thus, patterns of sex-associated seizure susceptibility favoring either males or females are both seizure- and stimulation-limited and do not reflect general dispositions to seizures in either sex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310948 TI - Responses of septal theta-on and theta-off cells to activation of the dorsomedial posterior hypothalamic region. AB - The effect of different levels of electrical stimulation of the dorsomedial posterior hypothalamic region, on the discharge properties of septal theta-on and theta-off cells, was investigated in urethane-anesthetized rats. In the present sample of 45 cells recorded in the medial septum/ventral limb of the diagonal band of Broca, 43 of the 45 (96%) were affected by the stimulation. The majority of theta-on cells were intensely activated by this stimulation (two were inhibited) and all theta-off cells were inhibited (ranging from partial to complete inhibition). Stimulation did not change a cell's classification as "on" or "off," nor did it alter its discharge pattern (phasic or tonic). Stimulation did have a profound effect on phasic nonlinear theta-on cells. Phasic nonlinear theta-on cells, by definition, did not alter their discharge rate in relation to the increasing frequency of spontaneously occurring or tail-pinch-induced theta. However, stimulation of the dorsomedial-posterior hypothalamus resulted in 11 out of 13 (85%) of the phasic nonlinear cells increasing their discharge rates in relation to the increasing frequency of the hypothalamically induced theta (i.e., became linear). Stimulation had no effect on two cells classified as unrelated to theta. PMID- 2310949 TI - Afferent fibers in the hypoglossal nerve: a horseradish peroxidase study in the cat. AB - The existence of afferent fibers in the cat hypoglossal nerve was studied by transganglionic transport of horseradish peroxidase (HRP). Injections of wheat germ agglutinin-conjugated HRP (WGA-HRP) into the hypoglossal nerve resulted in some retrograde labeling of cell bodies within the superior ganglia of the ipsilateral glossopharyngeal and vagal nerves. A few labeled cell bodies were also present ipsilaterally within the inferior ganglion of the vagal nerve and the spinal ganglion of the C1 segment. Some of the labeled glossopharyngeal and vagal fibers reached the nucleus of the solitary tract by crossing the dorsal portion of the spinal trigeminal tract. Others distributed to the spinal trigeminal nucleus pars interpolaris and to the ventrolateral part of the medial cuneate nucleus by descending through the dorsal portion of the spinal trigeminal tract. In the spinal cord these descending fibers, intermingling with labeled dorsal root fibers, distributed to laminae I, IV-V and VII-VIII of the C1 and C2 segments. Additional HRP experiments revealed that the fibers in laminae VII-VIII originate mainly from dorsal root of the C1 segment. PMID- 2310950 TI - Fetal hypothalamic brain grafts to the ventromedial hypothalamic obese rats: an immunohistochemical, electrophysiological and behavioral study. AB - Fetal ventromedial hypothalamic (VMH) tissue was transplanted into or around the third ventricle of adult Fischer 344 rats to determine if transplanted VMH tissue could reverse the hyperphagia and obesity produced by bilateral VMH electrolytic lesions. Host VMH-lesioned rats received stereotaxic implants of 13 to 19 postcoitus fetal VMH tissue from normal Fischer pups. The results show that: 1) Fetal VMH tissue survived in the brain (mainly in the third ventricle) of VMH lesioned rats. The optimal survival and differentiation was at the gestational age of 13 days; 2) VMH-lesioned rats containing VMH grafts tended to consume less food than the controls, but this was not statistically significant. Neural grafts that could compensate the hyperphagia and obesity produced by the VMH lesions (in comparison to the controls) were those placed into the third ventricle; 3) Electrophysiological evidence demonstrated that VMH grafts contain glucoreceptor neurons in grafts not only located in the third ventricle, but also in the thalamus; 4) Immunohistochemical evidence showed the presence of serotonin, beta endorphin and substance P immunoreactive fibers in the grafts. These results indicated that transplants of fetal VMH tissue in the brain of bilateral VMH lesioned adult rats may have some functional effects (depending on the location of the graft). PMID- 2310951 TI - On searching for the active sites in proteins and peptide hormones. AB - An essential part of structure-functional studies of proteins is the search for sites responsible for specific functional activity. The information theory can be of much help in such a search. According to this theory, rarely occurring oligomers contain more information and thus are more likely to take part in forming the active site. We used frequencies of occurrences of amino acids (mean and for each polypeptide) to search for clusters of highly informative amino acids by the moving window smoothing method. In 16 out of 19 peptide hormones such sequences were active sites known from literature. PMID- 2310952 TI - A fast algorithm for evaluating an approximation to the information enclosed within coronas and their sectors in square matrices. AB - From numerical data distributed in an even square matrix A, we wish to determine the proportion of the data belonging to a selected area (S). We restrict the problem to any field of the initial data square enclosed within the part of a corona (characterized by the real values of its two limiting radii) limited by a circular sector (defined by its two limiting angles), both corona and sector being centred at the centre of the square. A fast and accurate approximation algorithm is presented, which collects the contribution of all the pixels of A by exploration of the first quadrant. For each pixel of it and, at the same time, for its three symmetrical ones in the other quadrants, the program evaluates the part belonging to (S), using radial and angular factors. Finally, the weighted contributions are summed up. Compared to the classical methods (exact determination, testing the position of the pixel centres or others), this algorithm offers a better time/accuracy ratio. Suitable accuracy at the border makes it possible to choose larger pixel size, hence to spend shorter CPU time (even and especially in the case of thin rings with large radii). PMID- 2310953 TI - SIMFIT: a microcomputer software-toolkit for modelistic studies in biochemistry. AB - A software package suitable for personal computers and designed to handle simulation and fitting problems related to the study of biomolecules under pre steady and steady state conditions is presented, and its overall architecture as well as the implemented algorithms illustrated. The peculiar features of the package are: (i) integrated capability of simulating dynamic models and fitting to them experimental data; (ii) handling of stiff problems; (iii) free use of algebraic as well as differential equations; (iv) objective comparison of models of different complexity. The above features are discussed through a number of examples taken from the direct experience of the authors in enzyme kinetics and ligand binding. PMID- 2310954 TI - Analysis of mixed lipid extracts using 1H NMR spectra. AB - A method has been developed for rapid analysis of lipid proton NMR spectra. Identification of lipid content is possible because of the presence of unique peaks or ratios of peaks for individual lipids. Spectra can be subdivided into regions where peaks represent certain chemical groups held in common, or uniquely by the various lipids. Vectors (B) are made up of the areas of these subdivisions of peaks from spectra of unknown components. A new FORTRAN algorithm, LIPICK, tests for the presence of unique peaks or combinations of peaks to determine which lipids may be present. The spectra vectors of known identified lipids are then placed in the (A) matrix of possible solution candidates. Quantitation of lipids in an 1H NMR spectrum (B) of an unknown mixture then proceeds by solving the equation AX = B for X (the concentrations of the individual lipids present) by singular value analysis. At this time, it is possible to test 1 mg of total lipid for the presence and relative concentration of 15 common lipids: cholesterol and its esters; phosphatidyl-ethanolamine, -choline, -serine, inositol, -glycerol; tri- or di-glycerides; fatty acid; lysophosphatidylcholine; sphingomyelin; cerebrosides and sulfatides; dolichol and dolichol P; and phosphatidic acid. This procedure is suitable for membrane lipid analysis and has been evaluated using known mixtures of purified standard lipids. PMID- 2310955 TI - HCABAND: a computer program for the 2D-helical representation of protein sequences. AB - A BASIC program, HCABAND, is described which is used to convert the linear amino acid sequence of proteins into a word processor-readable file to generate the 2D helical representation required for hydrophobic cluster analysis. The user can specify the width of the plot and can use the word processor macro-commands to facilitate visual inspection of the plots. The plots can be easily stored on diskettes, mixed with text and printed. HCABAND features are generally applicable and can be implemented on virtually any microcomputer. PMID- 2310956 TI - Statistical significance of some complex nucleotide combinations: a comparison of DNA models. AB - DNA is modelled as a sequence of nucleotide runs. This model is shown to provide a more adequate description of the observed frequencies of occurrence of local homopurine-homopyrimidine mirror repeats than the second-order homogeneous Markov chain model. The procedure is described for estimating the statistical significance of the occurrence of some complex nucleotide combinations in DNA. PMID- 2310957 TI - Searching for tRNA genes in DNA sequences--an IBM microcomputer program. AB - A user-friendly program that enables fast and exhaustive searching for tRNA genes is presented. The program can run on IBM personal microcomputers and comprises modules for sequence editing and GenBank database access. PMID- 2310958 TI - Computer programs for the rapid determination of enzyme kinetics on MS-DOS compatible microcomputers. PMID- 2310959 TI - Basic program to assess the extent and pattern of agreement between two procedures. PMID- 2310960 TI - A simple method of hidden-line removal in three-dimensional modelling: hiding the problem behind filled polygons. PMID- 2310961 TI - Symposium on magnetic resonance imaging and spectroscopy honoring Andrei Sakharov. PMID- 2310962 TI - A 50-year-old woman with polymyositis and chronic bibasilar lung disease. PMID- 2310963 TI - Answer to Case of the Month #3. Pyogenic discitis. Staphylococcal discitis complicated by bilateral psoas abscesses. PMID- 2310964 TI - Role of MRI bone marrow imaging in recurrent lymphoma. PMID- 2310965 TI - International Society for Prevention of Child Abuse and Neglect--president's message: establishing priorities. PMID- 2310966 TI - Parental responses to extrafamilial child sexual assault. AB - Parents of a child who has been assaulted by someone external to the family are faced with the difficult task of dealing with their own reactions to the assault while attending to the needs of their children. Common emotional responses that parents express often fall into the following areas: guilt regarding failure as a parent; ambivalent feelings toward the child; ambivalent feelings toward the offender; and concerns about the investigatory and judicial processes. Clinical interventions with families which focus on support and education are suggested. In addition, systems changes, which demystify the court process and support victims, are recommended. PMID- 2310967 TI - Child physical and sexual abuse: the roles of sadism and sexuality. AB - Based on the analytical concepts of narcissism and perversion and clinical material, an hypothesis is presented for the understanding of the mental functioning of the physically and sexually abusive parent. Relating the aggressive instinct to narcissism and the sexual instinct to perversion, two modes of functioning are presented which have some points in common and some diverging but which show the dynamics involved in physical and sexual abuse. Understanding the type of emotional relationship between the parents and the type of their emotional investment in their child allows us to see how the complicity of parents works against the child. This understanding implicitly gives insight into the structuring of the personality of the child-victim, who in turn undergoes the risk of himself becoming a physically and/or sexually abusive parent with his own children. PMID- 2310968 TI - Syphilis as a sole indicator of sexual abuse: two cases with no intervention. PMID- 2310969 TI - Child abuse and neglect in a developing country. PMID- 2310970 TI - Sexual abuse in a national survey of adult men and women: prevalence, characteristics, and risk factors. AB - This paper reports on the first national survey of adults concerning a history of childhood sexual abuse. Victimization was reported by 27% of the women and 16% of the men. Higher rates of abuse were found among men who grew up in unhappy families, lived for some period with only their mothers, who were currently residing in the West and who came from English or Scandinavian heritage. Higher rates of abuse were found among women who grew up in unhappy families, lived for some period without one of their natural parents, received inadequate sex education, were currently residing in the West or who were born after 1925. PMID- 2310971 TI - The process of victimization: the victims' perspective. AB - Twenty-three child victims (aged 10-18 years) of childhood sexual abuse were interviewed about the victimization process, the person who abused them, and how abuse might have been prevented. Specific questions obtained information about the quality of the relationship between victim and offender, the offender's pre abuse behavior, the explanation for the behavior given by the offender, and the child's understanding of the behavior. Results suggest that the victimization process involves three overlapping processes: sexualization of the relationship, justification of the sexual contact, and maintenance of the child's cooperation. PMID- 2310972 TI - Maternal interactional behavior with nonorganic failure-to-thrive infants: a case comparison study. AB - Mothers of 47 6-month-old infants with early histories of nonorganic failure to thrive (NOFT) infants and a matched comparison group of physically healthy infants were observed in interactions with their infants in their homes one month following hospitalization. Mothers of NOFT infants were observed to have less adaptive social interactional behavior, less positive affective behavior, and demonstrated more arbitrary termination of feedings. No group differences were found in flexibility or sensitivity of maternal feeding, or in environmental circumstances such as number of persons present, noise level, or level of activity. These salient deficiencies in maternal interactional behavior may continue to disrupt the NOFT child's physical growth and psychological development following initial diagnosis and hospitalization. Additional studies are needed to identify patterns of maternal interactional behavior which influence psychological prognosis and to assess the responsiveness of maternal interactional behavior to intervention. PMID- 2310973 TI - Child sexual abuse: factors affecting victims' removal from home. AB - This study was conducted to examine factors associated with children's protective service workers' decision to remove sexually abused children from the family home. The decision to remove was analyzed relative to the following six factors: (1) nature of the abuse, (2) severity of abuse, (3) frequency of abuse (4) mothers' employment status, (5) mothers' compliance with a recommended treatment plan, and (6) mothers' belief of the victim. Discriminant function analysis revealed that the discriminant function containing mothers' compliance, mothers' belief, severity of abuse, mothers' employment status, and frequency of abuse, in order of importance of contribution, was significantly related to victims' removal from the home. PMID- 2310974 TI - Child sexual abuse: who goes home? AB - The purpose of this study was to ascertain the factors which influence custody change in cases of children who have been sexually abused. Of 180 children admitted to La Rabida Children's Hospital and Research center with a suspicion of having been sexually abused, 138 met the state's criteria for proven sexual abuse, and 30% of those children had a sexually transmitted disease. One-third of the children with proven abuse were under 4 years of age. Of the children with proven abuse, ultimately 40% had a custody change. Only an initial outcry of abuse was associated with an increased probability of a change in custody. A change in custody was not found to be related to the patient's age, sex, the perpetrator's relation to the child or access to the home, the presence of sexually transmitted disease, whether the child was also physically abused, or whether the child had had developmental delay. These data suggest an absence of any discernible guidelines in the juvenile court's decision concerning custody change of a sexually abused child. PMID- 2310975 TI - Professionals' adherence to mandatory child abuse reporting laws: effects of responsibility attribution, confidence ratings, and situational factors. AB - This study investigated the relationship between responsibility attribution and tendency to report child sexual abuse among practicing psychologists. Two hundred ninety-five licensed psychologists from two states completed vignettes in which the sex of the child and the father's admission or denial of alleged sexual abuse were systematically manipulated. Subjects assigned relative percentages of responsibility to the father, mother, child, and society for the abuse and indicated their tendency to report and their level of confidence that abuse was occurring. Results indicated a significant effect for responsibility to the mother which varied as a function of the father's response to the allegation of abuse. Mothers were blamed significantly more for the abuse when the father denied being abusive. Responsibility attribution did not predict reporting, while confidence in the occurrence of abuse did. Also, sex differences were found among participants where male subjects assigned significantly more responsibility to the abusive father than female participants, and the females blamed the mother more than the males. Results are discussed in the context of previous research on responsibility attribution in child abuse. PMID- 2310976 TI - Residents' attitudes toward the legal system and court testimony in child abuse. AB - Resident physicians' contacts with the legal system during management of abused children may influence their attitudes, which were evaluated in a pilot survey completed by 42 pediatric and medicine/pediatric residents. Although negative attitudes toward attorneys were common, almost all of the residents considered general and hearing-specific legal training to be a legitimate part of their residency program. They reported lower levels of stress of court testimony than expected by the authors. Most who had testified in court believed their testimony had been needed and helpful, but all who believed their testimony had been a waste of time were senior-level residents. Although most residents believed the laws and courts usually work for protecting children, only 8 of the 20 residents who had previously testified in court responded affirmatively, and none of the 10 senior residents who had previously testified held this belief. The disillusionment of senior-level residents appeared to affect attitudes toward patient care less than expected, in that 90% of those who planned to enter private practice indicated they would perform physical abuse evaluations and 70% planned to perform sexual abuse evaluations. Only one resident who did not expect to perform the evaluations gave as a reason the prospect of having to testify in court. PMID- 2310977 TI - Maltreatment among runaway and homeless youth. AB - A sample of 223 adolescents who sought services from runaway and homeless youth programs in New York State during 1986-1987 was identified as having a history of maltreatment. A demographic profile is presented and the nature of their maltreatment described. The majority of these youth were female and between 15-16 years of age. Less than 25% came from intact families and one-third were born to single mothers. Of the sample, 60% had allegedly experienced physical abuse, 42% emotional abuse, 48% neglect, and 21% sexual abuse. Over one-third were "pushed out" of their homes by their families. Biological mothers were the most frequently cited perpetrators of maltreatment (63%), followed by biological fathers (45%). The sample of maltreated runaways is compared to both statewide and national samples of runaway and homeless youth with regard to their demographic characteristics and the problems they present to staff at intake (e.g., depression, substance abuse, etc.). Youth in the maltreated sample were more likely to be female and were more likely to have engaged in suicidal behavior. Otherwise, the maltreated runaways were not readily distinguished from the runaway and homeless youth population at large. PMID- 2310978 TI - Developing guidelines for HIV antibody testing among victims of pediatric sexual abuse. AB - The incidence of human immunodeficiency virus (HIV) infection acquired by children through sexual abuse is presently unknown. A telephone survey of 63 practitioners of pediatric sexual abuse (PSA) assessment in the five U.S. regions with highest prevalence of HIV infection was conducted to determine the present status of guidelines for HIV antibody testing of PSA victims. No formal protocol was used by any of those surveyed, and a literature review found no existing guidelines for HIV antibody testing of PSA victims. A standard set of clinical situations was presented to practitioners to assess whether a consensus exists of indications for HIV antibody testing of abused children. Seven clinical profiles with 12 criteria were presented including HIV antibody status, AIDS/ARC clinical profile, and behavioral profile of the assailant; clinical profile of the victim; pre-assault victim behavioral profile compatible with high risk of HIV infection (exclusively adolescents); parent/guardian anxiety/psychosocial profile; and profile of the assaultive act with respect to potential transmissibility of HIV. We found an 85% or greater consensus for 6 testing criteria, and based upon these propose an interim set of HIV antibody testing guidelines for PSA victims. There was no consensus about five testing criteria, but their frequent citation merits further consideration. Clinical application of interim guidelines and design of prospective studies to quantitatively evaluate them are reviewed. PMID- 2310979 TI - The spectrum of low molecular weight house dust mite (Dermatophagoides pteronyssinus) allergens with emphasis on Der p II. AB - Analysis by protein blotting of sera from 96 different house dust mite-allergic subjects revealed previously unrecognized complexity of low molecular weight (MW) (less than 20 kD) IgE-binding proteins in extracts of whole bodies of Dermatophagoides pteronyssinus. Of 11 different IgE-binding components of MW less than 20 kD identified, two (MW approximately 16 kD and approximately 15 kD), showed both a high frequency (88% and 49% respectively) and a high intensity of IgE-binding. The approximately 16 kD component, identified as allergen Der p II, showed the highest frequency of IgE antibody reactivity of any of the major D. pteronyssinus allergens including Der p I and Der p III. PMID- 2310980 TI - The prevalence of allergic disease and IgE antibodies to house dust mite in schoolchildren in Taiwan. AB - The prevalence of positive specific IgE antibodies to house dust mites (Dermatophagoides pteronyssinus; D. farinae) was determined by enzyme-linked immunosorbent assay (ELISA) in 5097 (61%) volunteers of 8345 schoolchildren aged between 7 and 14 yr from two government schools. All of them filled out a questionnaire concerning allergic symptoms. Among them, 412 (8.1%) children showed a positive reaction to at least one of the two mite allergens, the range varying between 5.6 and 11.2% according to the child's age. Boys had higher prevalence of positive mite specific IgE than girls (9.8% vs. 6.4%, P less than 0.01), with the overall male to female ratio 1.5:1. The prevalence of bronchial asthma in boys and girls was 5.3% and 3.3% respectively. The positive mite specific IgE antibody in children with asthma and allergic rhinitis was 52% (103 of 198) and 28.7% (193 of 673) respectively. The mean levels of mite specific IgE were not significantly related to the age of onset and severity of asthmatic symptoms (P greater than 0.1), but were significantly different among subjects with current and past asthma (P less than 0.001). It is suggested that the mite specific IgE may play a role in the pathogenesis of bronchial asthma in children. PMID- 2310981 TI - Development of serum Dermatophagoides farinae-, ovalbumin- and lactalbumin specific IgG, IgG1, IgG4, IgA and IgM in children with bronchial asthma/allergic rhinitis or atopic dermatitis. AB - Dermatophagoides farinae-, ovalbumin- and lactalbumin-specific IgG, IgG1, IgG4, IgA and IgM were evaluated in 161 healthy children [Group 1], 84 children with bronchial asthma and/or allergic rhinitis but without atopic dermatitis [Group 2], and 54 children with atopic dermatitis but without bronchial asthma and allergic rhinitis [Group 3]. We also studied D. farinae-, egg-white-, and milk specific IgE of children with allergic diseases. D. farinae-specific IgG, IgG1, IgG4 and IgA in Groups 2 and 3 increased until 5 years of age and thereafter they remained constant. After 2 years of age, D. farinae-specific IgG, IgG1, IgG4 and IgA in Group 2 were higher than those in Groups 1 and 3. Ovalbumin- and lactalbumin-specific IgG, IgG1, IgG4 and IgA in Groups 2 and 3 increased until 1 year of age and thereafter decreased. Until 1 year of age, ovalbumin- and lactalbumin-specific IgG, IgG1 and IgG4 in Groups 3 were higher than those in Groups 1 and 2. D. farinae-, ovalbumin- and lactalbumin-specific IgM were constant in all ages of all groups. These results suggest that atopic dermatitis in young children is related to food-specific immunoglobulins and that respiratory allergic diseases in older children is related to D. farinae-specific immunoglobulins. PMID- 2310982 TI - Mast cells in cutaneous mastocytosis: accumulation of the MCTC type. AB - Lesional (n = 15) and non-lesional (n = 10) skin of subjects with mastocytosis was analysed for the distribution and concentration of trypase positive, chymase negative mast cells (MCT) and tryptase positive, chymase positive mast cells (MCTC) cells and compared to normal skin (n = 23) and non-lesional skin of subjects with unexplained anaphylaxis or flushing episodes (n = 6). Skin biopsies were fixed in Carnoy's fluid and subjected to double immunohistochemical staining with biotinylated mouse monoclonal anti-chymase antibody followed by alkaline phosphatase-conjugated mouse monoclonal anti-tryptase antibody. MCTC cells were the only type of mast cells seen in all specimens analysed and in each case were more numerous in superficial compared to deep regions of dermis. The concentration (mean +/- s.d.) of mast cells in the superficial dermis of mastocytosis lesions (40 985 +/- 21 772 mast cells/mm3) was significantly increased over that in corresponding areas of non-lesional skin from subjects with mastocytosis (7178 +/- 3607 mast cells/mm3), skin from subjects with idiopathic anaphylaxis or flushing episodes (6974 +/- 3873 mast cells/mm3) and normal skin (7347 +/- 2973 mast cells/mm3). The exclusive presence of MCTC cells in skin lesions of mastocytosis which are characterized by non-malignant hyperplasia of mast cells suggests involvement of local tissue factors in mast cell recruitment and differentiation. PMID- 2310983 TI - Shared and specific allergenic and antigenic components in the two sexes of American cockroach--Periplaneta americana. AB - The whole body extracts (WBEs) of female and male cockroaches (Periplaneta americana; Pa) were prepared separately to study the specific and/or shared allergenic and antigenic components in the two sexes. These two extracts were skin-tested on 170 respiratory allergy patients and 52 (30.6%) of them elicited a markedly positive cutaneous reaction (2+ to 4+) to any one or both the WBEs. Of these 52 patients, 32 (61.5%) produced a 2+ to 4+ response to only one, and the remaining 20 (38.5%) to both the extracts. In female and male RASTs to Pa both the extracts produced dose-related inhibition. Using rabbit anti-Pa female serum: (1) immuno-diffusion experiments resulted in lines of identity with the two extracts, and (2) the two-dimensional immunoelectrophoresis of Pa female and Pa male WBEs elicited 12 and nine precipitin peaks, respectively. In partial purification studies, only fraction Pa(F)III (approximately 50 kD) of Pa female WBE and Pa(M)I (greater than or equal to 600 kD) and Pa(M)III (approximately 50 kD) fractions of Pa male WBE revealed significant allergen activity both on skin testing and also in RAST inhibition studies. These results provide evidence for the presence of shared as well as specific allergenic and antigenic components in the two sexes of American cockroach. PMID- 2310984 TI - The relationship between anti-IgE auto-antibodies and the IgE response to wasp venom during immunotherapy. AB - During immunotherapy with wasp venom, levels of venom-specific IgE antibodies increase and then fall, whereas the concentration of IgG antibodies rises and then remains at a high level. Successful treatment is therefore associated with both increased concentrations of serum IgG and decreased serum IgE antibodies to venom. In this study we have investigated the possible role of auto-antibodies in inducing the decrease in serum IgE antibody. Levels of auto-anti-IgE were measured by a radioimmunoassay. Anti-IgE auto-antibodies were not generated during immunotherapy and there was no significant difference in the levels of anti-IgE auto-antibodies between patients whose venom-specific IgE antibody levels fell more than fivefold after immunotherapy and those patients in whom IgE antibody levels did not change significantly. We conclude that anti-IgE auto antibodies do not play a part in IgE suppression induced by immunotherapy. PMID- 2310985 TI - Allergy to mice. II. Further characterization of two major mouse allergens (AG 1 and AG 3) and immunohistochemical investigations of their sources. AB - Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and quantitative immunoelectrophoretic techniques have been used to characterize further the two major mouse allergens, antigen 1 (Ag 1) and antigen 3 (Ag 3). Gel filtration using Sephacryl S-200 showed Ag 1 to have a molecular weight of 18 kD and Ag 3 of 21 kD. SDS-PAGE followed by Western blotting onto nitrocellulose then incubation with individual antisera directed against each of the two major allergens, and an alkaline phosphatase enzyme system, was used to distinguish between the two allergens and indicated a molecular weight of 17 kD for Ag 1 and 16 kD for Ag 3. Ag 3 but not Ag 1 was shown to contain polysaccharide residues. Immunohistochemical staining of mouse skin sections demonstrated that antigens detected in whole dust extracts were present in the hair follicles, on the hair shafts and on the stratum corneum. Staining of similar sections using the rabbit anti-Ag 3 showed the presence of this major allergen in the hair follicles coating the hairs and extending along the skin surface. Serum from a pool of mouse-allergic subjects also demonstrated staining in the same areas when detected using a fluorescein-labelled anti-human IgE as second antibody. As both major allergens were present in extracts of fur this would appear to be most appropriate for use in diagnosis (i.e. skin test and RAST) and also possibly desensitization. However, dust from isolators (available in greater amounts) would be equally suitable. PMID- 2310986 TI - Fluid and electrolyte therapy. PMID- 2310987 TI - Oral electrolyte replacement solutions. PMID- 2310988 TI - Parenteral electrolyte replacement solutions. PMID- 2310989 TI - Conversion from intravenous procainamide to oral sustained release tablets in cardiac patients. AB - There is as yet no established method for converting from intravenous to oral sustained release procainamide (Procan SR; Parke-Davis Canada Inc). The pharmacokinetics of simultaneous discontinuation of intravenous procainamide and administration of oral sustained release procainamide was studied in six patients with ventricular tachyarrhythmias. Patients were converted after ensuring that steady-state concentrations were achieved with intravenous procainamide. Serum procainamide levels were obtained at the time of conversion and 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 6.0 h after conversion. The mean steady-state concentration (23.7 +/- 8.9 mumols/L) and the adjusted mean serum procainamide concentration with Procan SR (25.3 +/- 7.9 mumols/L) were not significantly different. This indicated that the serum procainamide concentration obtained with the intravenous infusion was not compromised when the patients were switched to oral therapy. Although mean percentage serum procainamide concentration fluctuation was 102.6 +/- 92.5, all patients tolerated the conversion well. Therefore, the method used in this study is an acceptable method of conversion. PMID- 2310990 TI - Inaccuracy of Doppler estimates of pulmonary artery pressure using pulmonary flow acceleration time. AB - Pulsed Doppler echocardiography was used to estimate mean pulmonary artery pressure (PAP), mean pulmonary artery wedge pressure PAWP) and the changes in PAP and PAWP following intervention in an unselected population composed of 60 patients undergoing routine diagnostic cardiac catheterization. Simultaneous Doppler and strain gauge manometry recordings of PAP and PAWP were interpreted by independent observers in a blinded fashion. A first set of measurements was obtained before left ventricular angiography and a second soon after the injection of contrast dye. The mean Doppler PAP and PAWP were derived from acceleration time and calculated using previously published regression equations: PAP = -0.45 x AcT + 79, PAWP = 57 - 0.39 x AcT. At rest, PAP measurements by strain gauge manometry ranged from 13 to 45 mmHg with a mean of 24 +/- 10 (one standard deviation); PAWP ranged from 2 to 40 mmHg with a mean of 15 +/- 6. Following left ventricular angiography, the PAP ranged from 18 to 50 mmHg with a mean of 29 +/- 7; PAWP ranged from 6 to 45 mmHg with a mean of 20 +/- 7. The values obtained by pulsed Doppler before and after intervention correlated poorly with those obtained by strain gauge manometry (r = 0.09 and 0.26 for PAP; r = 0.03 and 0.25 for PAWP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310991 TI - Chronic aortic regurgitation: a demonstration of the effect of bradycardia on left ventricular function. AB - A 50-year-old man with previously asymptomatic aortic regurgitation presented with clinical, echocardiographic and hemodynamic deterioration secondary to bradycardia. The effects of prolonged diastolic time were demonstrated in the catheterization laboratory; immediate improvement in left ventricular end diastolic and aortic diastolic pressures were noted after the insertion of a temporary pacemaker at a heart rate of 70 beats/min. In patients with aortic regurgitation and unexpected deterioration, bradycardia should be considered. PMID- 2310992 TI - Hemoptysis: two unusual causes. AB - Hemoptysis is most commonly due to pulmonary pathology. When cardiac in origin it is usually due to mitral valve disease. The authors present two unusual causes of hemoptysis: cor triatriatum and primary cardiac liposarcoma. PMID- 2310993 TI - Long acting calcium antagonist anipamil limits myocardial necrosis and penetrates the ischemic zone during 24 h of coronary artery occlusion in the dog. AB - This study examined the effect of the long acting calcium antagonist anipamil on the extent of myocardial necrosis during 24 h of coronary artery occlusion in the dog. Forty dogs had coronary artery occlusion with a 2 mm embolus injected into the left coronary system; 141 cerium microspheres were used to delineate the ischemic zone immediately following occlusion. Twenty dogs received no drug (controls) and 20 received anipamil (two boluses of 0.25 mg/kg intravenously, one within 5 mins of occlusion and the other 12 h later). Arterial pressure and heart rate were monitored for 24 h. A subgroup of five controls and four anipamil treated dogs had injections of a second microsphere (113 tin or 46scandium) at 24 h to show changes in bloodflow. At 24 h the surviving dogs were sacrificed, their hearts sectioned, the risk zones delineated by autoradiography and the necrotic zones delineated by tetrazolium staining. Samples were taken from the normal myocardium and the risk zones for a determination of tissue anipamil content and measurement of regional bloodflow. In the control hearts, 76 +/- 4% of the risk zones became necrotic after 24 h, compared with 53 +/- 4% in the anipamil treated group (P less than 0.005). Anipamil had no effect on the heart rate or the arterial pressure. In the control dogs, the bloodflow to the tissue that became necrotic was 17% of the normal flow immediately after coronary occlusion, and 16% at 24 h; flow in the viable (subepicardial) tissue was also unchanged (49 versus 54%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310994 TI - The effect of lactate infusion on myocardial metabolism and ventricular function following ischemia and cardioplegia. AB - Impaired myocardial fatty acid and glucose metabolism following ischemia and cardioplegia may limit the recovery of myocardial oxidative metabolism and ventricular function. Lactate, a simple three carbon compound, can be readily metabolized to pyruvate and is possibly the preferred substrate for aerobic metabolism. Therefore, increasing arterial lactate concentrations may improve myocardial metabolic recovery after ischemia and cardioplegia. Myocardial lactate metabolism and ventricular function were assessed in a canine model of 45 mins of global normothermic ischemia followed by 60 mins of cold potassium cardioplegic arrest. Thirteen dogs received a perioperative infusion of sodium lactate to elevate arterial concentrations (from 6 to 12 mmol/L) and 12 dogs received an equivalent amount of saline. The high arterial lactate concentrations were associated with an increased myocardial lactate consumption and oxidation (as assessed by 14C-labelled lactate) during reperfusion. Myocardial ATP concentrations fell during reperfusion despite improved myocardial oxidation. The recovery of ventricular function (as assessed by a compliant intraventricular balloon) was incomplete and only marginally better with the high arterial lactate concentrations. An infusion of lactate improved myocardial oxidative metabolism following ischemia and cardioplegia. However, the recovery of ventricular function was incomplete perhaps because of inadequate preservation of myocardial ATP. PMID- 2310996 TI - Total and coronary heart disease mortality in relation to major risk factors- Quebec cardiovascular study. AB - The relationships of blood pressure, smoking, serum cholesterol and education levels on total and coronary artery disease (CAD) mortality were evaluated in 4576 Quebec men aged 35 to 64 years, free from overt CAD at entry and followed for 12 years. From January 1974 to January 1986, there were 417 deaths, 131 due to CAD. A progressive increase in total and CAD mortality was observed from quintile 3 to 5 for both systolic and diastolic blood pressure. In comparison to quintile 1, the adjusted relative risks of quintiles 4 and 5 for systolic blood pressure were significantly elevated (2 P less than 0.01), being 1.5 and 2.0 for total mortality, and 2.6 and 3.5 for CAD mortality, respectively. The relative risks of quintiles 4 and 5 for diastolic blood pressure were also significantly elevated (2 P less than 0.04), being 1.5 and 1.6 for total mortality and 1.9 and 2.7 for CAD mortality, respectively. In comparison to those who never smoked, the relative risks of smoking one to 20, and 21 and more cigarettes per day, were 2.1 (2 P less than 0.003) and 3.1 (2 P less than 0.0001) for overall mortality, and 2.2 (2 P less than 0.08) and 3.5 (2 P less than 0.002) for CAD mortality. Men who had discontinued smoking at least one year before the study, had a relative risk not different from those who had never smoked. Serum cholesterol and education levels were not significantly associated with total or CAD mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310997 TI - Rupture of both left ventricular papillary muscles following acute myocardial infarction. AB - A 77-year-old woman collapsed shortly after arrival at the emergency department and attempts at resuscitation were unsuccessful. Autopsy revealed an evolving recent transmural myocardial infarct in the posterolateral free wall of the left ventricle with rupture of both papillary muscles. No well documented description of post infarction dual papillary muscle rupture was found in the literature. PMID- 2310995 TI - Dipyridamole testing compared to exercise stress for thallium-201 imaging in patients with left bundle branch block. AB - Because of numerous reports of false positive results with thallium-201 (Tl-201) stress testing in patients with left bundle branch block, the authors decided to evaluate another mode of coronary vasodilatation, dipyridamole, for the diagnosis of coronary atheromatosis. Nine patients were prospectively studied with stress and dipyridamole Tl-201 scintigraphy; both tests were performed within three to 79 days of one another. Five of the patients also had coronary angiograms (four within one year, one five years earlier). Four of the patients had normal results with both tests (two normal angiograms, two not performed); two had reversible septal defects with stress-induced coronary vasodilatation but normal dipyridamole studies (only one had an angiogram, which was normal); one patient had a fully reversible septal defect with stress and a fixed defect with dipyridamole (normal angiogram); one had a partially reversible septal stress defect which was fixed with dipyridamole; and one had a normal stress study but a reversible septal defect with dipyridamole (an angiogram performed five years earlier showed 30 to 40% stenosis of the anterior descending artery). Because it seems that dipyridamole produces fewer false positive results, it should be used instead of stress testing to induce coronary vasodilatation in patients with left bundle branch block. PMID- 2310998 TI - Assessment of ischemic injury and protective interventions: the Langendorff versus the working rat heart preparation. AB - The isolated rat heart is widely used for investigating ischemia and evaluating protective interventions, particularly with global ischemia, in which Langendorff and working preparations have formed the cornerstone of much of the developmental work on cardioplegic solutions. The objective of the present study was to compare the vulnerability of the two preparations to global ischemia and their responsiveness to protection with the St Thomas' Hospital cardioplegic solution. Langendorff preparations (n = 6) were subjected to 15, 30, 45, 60, 75, 90, 105 or 120 mins of global ischemia, and working preparations (n = 6) to 10, 15, 20, 25, 30, 35, 40 or 45 mins of global ischemia; post ischemic recovery of cardiac function, creatine kinase leakage, tissue ATP and creatine phosphate content were measured. With 30 mins of global ischemia, the impairment of cardiac function was similar in both preparations. With reperfusion in the Langendorff, the left ventricular developed pressure (LVDP), maximum rate of pressure development (dP/dt), heart rate and coronary flow recovered to 54.7 +/- 5.7, 53.7 +/- 7.1, 88.9 +/- 3.0 and 67.2 +/- 1.8%, respectively, of their pre-ischemic control value. In working hearts, cardiac output, heart rate and coronary flow recovered to 17.9 +/- 2.5, 95.6 +/- 4.2 and 73.8 +/- 8.2%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2310999 TI - Absence of prejunctional sympathetic effect of amiodarone in hearts of open-chest anesthetized dogs. AB - The effect of amiodarone (30 mg/kg p.o. each day for 3 weeks) on noradrenaline (NA) overflow into coronary sinus (CS) blood during left stellate stimulation (15 V, 2-ms square waves, 30 s duration at 1, 2, 4, and 8 Hz in random order) was investigated in an open-chest dog preparation. CS blood samples were taken before and during the stimulation period for plasma NA and hematocrit determinations. CS blood flow was monitored (extracorporal circulation with an electromagnetic flow meter) and used for NA output computation. The right atrium was paced throughout the experimental period. However, because AV block occurred at a high pacing rate in some amiodarone-treated dogs, pacing rate was lower in that group than in control dogs (132 +/- 13 vs. 161 +/- 10 min-1, ns). Mean arterial pressure was also lower in the treated group (95 +/- 9 vs. 110 +/- 13 mmHg, but increased in every dog upon stimulation (p less than 0.05). Basal left ventricular dP/dtmax was comparable in the two groups of dogs and increased in a similar fashion upon stimulation (p less than 0.05). The increase in plasma NA concentration upon stimulation was comparable between the control and the amiodarone-treated group (0.38 +/- 0.08 vs 0.40 +/- 0.12 ng/mL at 1 Hz and 12.7 +/- 3.1 vs 11.3 +/- 2.3 ng/mL at 8 Hz, ns). The increase in NA output was also comparable (7.0 +/- 1.6 vs. 10.7 +/- 5.4 ng/min at 1 Hz and 356 +/- 124 vs. 334 +/- 102 ng/min at 8 Hz, ns). Amiodarone did not alter the myocardial NA content. We conclude that amiodarone, administered orally for 3 weeks, does not interfere with neural NA release, or with the positive inotropic response, following sympathetic nerve stimulation in dogs. PMID- 2311000 TI - The role of ATP in energy-deprivation contractures in unloaded rat ventricular myocytes. AB - Energy-deprivation contractures were investigated in unloaded rat ventricular myocytes. Application of 2 mM cyanide in the presence of 10 mM 2-deoxyglucose (metabolic blockade) led to a rapid shortening "contracture" (maximum speed 1.5 +/- 0.2% control cell length/s). Cells shortened to a constant length of 69 +/- 1.6% of the control length. Removal of cyanide caused cells to shorten further ("recontracture"), before relaxing towards the control length. Cells shortened to 57 +/- 2.0% during the recontracture. Similar behaviour was observed in zero extracellular [Ca2+]. Cells permeabilized with saponin (0.1% w/v) responded to the removal of ATP from the bathing solution, and to readdition of ATP, as intact cells did to complete metabolic blockade and its removal. In these permeabilized cells, the extent and speed of contracture shortening were similar at pCa = 7 and pCa greater than 9. When the bath concentration of ATP ([ ATP]b) was lowered to zero, shortening stopped at about 70% of the control length. However, when [ATP]b was lowered to an intermediate level (4-20 microM), cells contracted to lengths as short as 30% of the control length. Similarly, when [ATP]b was restored from zero to an intermediate concentration (4-20 microM), recontracture shortening continued without relaxation. The peak speed of this Ca2(+)-independent shortening showed a sigmoidal dependence on pMgATP (pMgATP0.5 = 4.0). Phosphocreatine (10 mM) shifted the ATP dependence of Ca2(+)-independent shortening to lower [ATP]b (pMgATP0.5 = 5.0), suggesting that gradients of [ATP] could exist between the bath and the myofilaments. Ca2(+)-independent shortening was inhibited by the chemical phosphatase 2,3-butanedione monoxime (BDM), although BDM did not relax cells from the shortened state during energy deprivation. Using a simple model, we show that the results can be explained by cross-bridge cycling occurring independently of Ca2+ over a "window" range of [MgATP] (0.1-100 microM). Therefore, when [MgATP] falls, cross-bridge cycling occurs and the cell shortens. As [MgATP] falls to very low levels ([ MgATP] less than 1 microM), shortening ceases as the rate of cross-bridge cycling declines. Recontracture occurs on restoring ATP production, because stiffness falls and Ca2(+)-independent cross-bridge cycling initially increases. As [MgATP] rises above 100 microM, Ca2(+)-independent cross-bridge cycling ceases and the cell relaxes towards the control length. We conclude that energy-deprivation contractures, and recontractures, can result from changes in [MgATP] and do not necessarily require changes in [Ca2+]i. PMID- 2311001 TI - Beta-lactoglobulin enhances the uptake of free palmitate by hepatocyte monolayers: the relative importance of diffusion and facilitated dissociation. AB - We compared the uptake of bound palmitate by rat hepatocytes to its uptake by polyethylene using beta-lactoglobulin (BLG) as the binding protein. The experiments were designed to supply a direct measure of the protein-dependent change in the diffusive conductance of extracellular fluid without determining the diffusion coefficients for free and bound fatty acid or the off-rate constant for protein binding. Rate-limiting dissociation in the stirred phase of extracellular fluid was excluded. The results obtained with BLG are strikingly similar to those previously obtained with albumin and provide additional circumstantial evidence that when the free fraction is small, palmitate uptake is partially driven by the concentration of bound fatty acid. Because this phenomenon is not specific for the binding protein, it may reflect direct exchange of ligand between the binding protein in extracellular fluid and the putative transport protein in the hepatocyte plasma membrane. PMID- 2311003 TI - Symposium. Nausea and vomiting: a multidisciplinary perspective. Ottawa, Ontario, November 12-13, 1988. PMID- 2311002 TI - The cardiac contractile function and hemodynamic control in rats after chronic adriamycin treatment. AB - Cardiac contractile function and hemodynamic parameters of control and adriamycin treated (2 mg/kg once a week for 10 weeks) rats were studied both in the anesthetized (hexenal, 20 mg/kg) and conscious state. Radiolabelled microspheres (diameter, 15 microns) were used to measure systemic and regional hemodynamics. No significant differences between the control and adriamycin-treated groups in cardiac contractile function, total peripheral resistance, and regional blood flow (except muscles) was found in anesthetized animals. In the conscious state, a significantly higher (+70%) total peripheral resistance combined with lower blood flow in the skin and spleen was observed in adriamycin-treated rats. The response of the heart rate to changes in the arterial pressure induced by nitroglycerin and phenylephrine injection was greatly diminished after adriamycin treatment. Isoprenaline (0.64 micrograms.kg-1.min-1) increased left ventricular contractile indices approximately twofold and heart rate by 30% in the control group, while in adriamycin-treated rats only minor changes in these parameters were observed. However, cardiac output rose by 36% and total peripheral resistance fell by 36% in these animals. Results show that prolonged adriamycin treatment leads to decreased inotropic response to beta-adrenoceptor stimulation and reduced baroreflex control. These changes occur in the stage preceding congestive heart failure. PMID- 2311004 TI - Conditioned taste aversion and motion sickness in cats and squirrel monkeys. AB - The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea. PMID- 2311005 TI - The neuropharmacology of emesis: the role of receptors in neuromodulation of nausea and vomiting. AB - The basic pharmacological mechanisms involved in mediating nausea and vomiting are still poorly understood. Several classes of drugs have been identified that alleviate the symptoms of nausea and vomiting, either prophylactically or acutely. None of these is completely effective in all cases. They include antihistamines, dopamine antagonists, steroids, cannabinoids, benzodiazepines, serotonin antagonists, and anticholinergics. This paper examines the evidence that links each of these classes of drugs with the distribution of specific neurotransmitter receptor sites on which they may be acting. Studies on the central nervous system distribution of binding sites for one of these classes of drugs, the anticholinergics, are described. Binding sites for the muscarinic cholinergic radioligand [3H]quinuclidinylbenzilate occur in different concentrations throughout the dorsal vagal complex of the rabbit medulla oblongata. The distribution of such sites in this nonvomiting experimental animal is markedly different from that in the cat, an animal that has been used for many physiological and pharmacological studies of emesis. A previous study has suggested that muscarinic binding sites may occur presynaptically on vagal afferent terminals that synapse in the dorsal vagal complex of the cat; this appears not to be the case in the rabbit. Possible implications of these findings for the identification of the site of action of anticholinergic, antiemetic drugs are discussed. PMID- 2311006 TI - Promoting OR education. The need is now! PMID- 2311007 TI - Recovery room nursing. Spinal narcotics. Implications for nursing. PMID- 2311008 TI - Legal woes of incomplete intraoperative charting. PMID- 2311009 TI - Professionalism and the O.R. nurse. PMID- 2311010 TI - 18Fluorodeoxyglucose positron emission tomography studies in presumed Alzheimer cases, including 13 serial scans. AB - Positron emission tomographic (PET) data on local cerebral metabolic rates for glucose (LCMR) are reported for 32 regions of interest (ROI)s in cross-sectional studies on 57 patients with clinically diagnosed Alzheimer's disease (AD) and 20 neurologically normal controls, and in serial studies on 13 of the AD cases, including a familial, young-onset case where the diagnosis has been confirmed at autopsy. Extensive psychological testing was done on all the AD cases. Almost all cortical regions showed a significant decline in LCMR with age in the control subjects. There were the expected cortical metabolic deficits in AD and the serial studies showed a general increase in such deficits over time in 12 of the 13 cases. The regions showing the greatest declines with time in serial studies are the same as those showing the most severe deficiencies in cross-sectional studies. The young-onset case did not show a greater rate of metabolic decline than many of the older cases studied. Results on individual psychological tests tended to correlate with metabolic rates in multiple, rather than single, cortical regions, suggesting intact neuronal networks are required for good performance. The correlations with cortical metabolic activity found were of a sign indicating that the higher the metabolic rates and the better the left:right asymmetry index, the better was the performance. PMID- 2311011 TI - Association between Alzheimer disease and amyotrophic lateral sclerosis? AB - We report two cases of Alzheimer disease (AD)--one of them familial--in which the patient also had amyotrophic lateral sclerosis (ALS), and one patient with familial AD who had a son with ALS. Three further cases of probable ALS were found in pedigrees of AD reported from the literature. It is proposed that this association is not coincidental, but may suggest an etiological factor in common. PMID- 2311012 TI - Absence of responses to microstimulation at the hand-face border in baboon primary motor cortex. AB - Intracortical microstimulation (ICMS) was used to map the primary motor cortex of four adult female baboons, anesthetized with a mixture of halothane and nitrous oxide and supplemented with sodium pentobarbital. The sequence of observed muscle contractions in response to ICMS provided evidence of an orderly mototopic representation of the tongue, face, hand, forearm and upper body. A zone of cortex unresponsive to microstimulation was consistently observed at the border between the face and hand representation of the mototopic map. This zone was observed in all four animals and was consistent over time. Repeated confirmations of the unresponsive nature of these regions were obtained both early and late in the same experiment. No motor-unit responses or muscle contractions were detected by electromyographic (EMG) recording during stimulation of the unresponsive zones. The absence of both visually observed and EMG-recorded contractions and the fact that muscle contractions could be elicited from adjacent regions of cortex with ICMS as low as 1-5 microA provide compelling evidence that the finding reflects a true physiological condition rather than an experimental artifact. PMID- 2311013 TI - Receptive-field size of S1 cortical neurones is altered by methaqualone via a GABA mechanism. AB - Methaqualone (Mtq; quaaludes or 'ludes) is a controlled substance, having a molecular structure related to the imidiazobenzodiazepine series of drugs, that has gained some notoriety recently due to its history of widespread abuse on the street. Users report experiencing peripheral paresthesia and transient numbness on body parts receiving dense cutaneous innervation (lips, fingertips, etc.). Since the receptive-field (RF)-sizes of many primary somatosensory (S1) cortical neurones are controlled by local, gamma-aminobutyric acid (GABA)-mediated inhibitory processes, we tested Mtq to see whether its clinical symptoms might have a basis in an action through central GABA-mediated synaptic processes. This report supports this contention and describes a likely pharmacological mechanism involved as one being related to the Ro 15-1788-sensitive benzodiazepine (Bzd) recognition site(s) of the GABA receptor complex. PMID- 2311014 TI - PET, CT, and MRI imaging of neuronal migration anomalies in epileptic patients. AB - During the investigation of intractable epilepsy, neuronal migration anomalies [NMA] were discovered in three patients. The first patient had abnormally positioned gray matter within the walls of both lateral ventricles. The second patient had a post operative cystic area in the right parietal-occipital lobes and an area of NMA within the right temporal lobe. The third patient had abnormally thickened gray matter in the right operculum. Long term CCTV-EEG monitoring of these three patients revealed ictal discharges originating from the area of abnormal gray matter in patients 2 and 3. PET scanning showed the areas of NMA in all three patients to have similar metabolic activity to normal gray matter. These cases illustrate the value of various imaging modalities and suggest some interesting physiology of a spectrum of neuronal migration anomalies. PMID- 2311015 TI - Acute transverse myelopathy in children. AB - Twenty-three children with acute transverse myelopathy (ATM) are reviewed. Antecedent minor trauma or exercise was reported in 10 patients. Despite a positive history in 7 patients no preceding infection was documented. Two patients had a history of less severe ATM followed by recovery prior to a second more severe episode. The most common initial symptom was back pain and the most prominent clinical signs were weakness, sensory level and sphincter disturbances. Myelography and CT myelography at presentation was performed to exclude a compressive lesion. Spinal cord enlargement was demonstrated in 6 of 21 cases. Magnetic resonance imaging (MRI) of the spinal cord, performed in one patient, showed enlargement of the cord. Poor prognostic features were severity of weakness at the time of maximum deficit and a delayed onset of recovery. Maximum motor recovery occurred at a mean of 6 1/2 months but did not occur in one patient until 1 1/2 years. Normal or good outcome was obtained in 64%. PMID- 2311016 TI - Late pseudo-exacerbation of myasthenia gravis due to ectopic thymoma invading lower cranial nerves. AB - Dysarthria, dysphagia and repeated aspiration in a 54-year-old woman diagnosed and treated for myasthenia gravis 7 years earlier were initially thought to represent a late exacerbation of myasthenia. A cervical mass invading the jugular foramen and causing multiple lower cranial nerve palsies was biopsied and found to represent invasive ectopic thymoma. PMID- 2311017 TI - [Neurosurgery and creativity]. PMID- 2311018 TI - The Second Canadian Conference on Multiple Sclerosis. AB - The epidemiology of multiple sclerosis (MS) and the planning and i interpretation of clinical therapeutic trials were the subjects of a symposium on MS held on June 13, 1989. Several speakers addressed whether MS is a genetic or an environmental disease. An environmental trigger would resolve the relatively low penetrance of the disease in susceptible individuals, although the alternative hypothesis that MS is a multigenic disease would also account for this observation. Clinical trials have to date failed to confirm the efficacy of any immunosuppressive or other agent in the management of progressive MS. Magnetic resonance imaging (MRI) appears to be highly sensitive for monitoring the activity of MS. Preliminary evidence suggests that MRI activity correlates with longitudinal clinical assessments of disability. Immunologic tests, while valuable in determining pathophysiology of MS, have not been strongly correlated with clinical outcome. PMID- 2311019 TI - Surgical management of giant pituitary adenomas. AB - During the past 25 years, 77 giant pituitary adenomas have been treated surgically, including suprasellar extensions of type C in 66 cases and of type D in 11 cases. Non-secreting adenomas were present in 53 and secreting adenomas in 24 cases. All patients except 3 presented with significant visual field defects; including bitemporal hemianopia, superior quadranopia or unilateral temporal hemianopia, contralateral blindness in 73% of the cases, and one case with sudden bilateral blindness due to acute pituitary apoplexy. A single transsphenoidal procedure was carried out in 74% of the patients while 11 patients (7%) required re-operations for recurrent or residual tumor. Only 3 patients required a subsequent transcranial procedure. Complications included 1 CSF-leak, 1 empty sella syndrome and 4 fatal post-operative hematomas. We prefer the transsphenoidal route even in very large or giant pituitary adenomas, since it allows rapid and adequate decompression of the optic nerves and chiasm, avoids major pituitary insufficiency in 60% of the cases and is associated with low morbidity-mortality rates. PMID- 2311020 TI - Prolactin-secreting adenomas--surgical results. AB - The long-term follow-up of the transsphenoidal microsurgical treatment in 119 consecutively operated women with a PRL-secreting adenoma is presented. An apparent total removal of the tumor was achieved in 98 cases with an enclosed tumor (58 grade 1 and 40 grade II). In the remaining cases the removal was considered partial. The achievement of persistent normal PRL basal levels was verified in 61 patients (44 grade I and 17 grade II) who had an apparent total removal of the adenoma. In the 37 remaining patients who were thought at surgery to have had total removal we have distinguished two groups: 30 patients showed a "relapse" or "persistence" of PRL levels below 200 ng/ml without clinical and radiological signs of tumor regrowth, and 7 patients with a PRL level higher than 200 ng/ml who had evidence of PRL-secreting tumor recurrence. PMID- 2311021 TI - Results of primary treatment with bromocriptine of prolactinomas with extrasellar extension. AB - Nineteen patients, seven women and twelve men, with macroprolactinomas characterized by extrasellar extension and basal prolactin levels above 6 U/l were treated with 10-20 mg bromocriptine daily in four divided doses for a mean period of 3.4 years (range 1.5-5.5 years). Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in sixteen patients. Tumor size was reduced by more than 75% in seventeen patients and by 50-75% in two patients. Tumor reduction was associated with the development of a partial empty sella in fourteen cases. In seventeen cases the pituitary became visible. Diminished visual acuity (six patients), bitemporal hemianopia (nine patients), unilateral and bilateral central scotomas (three patients) and oculomotor palsy (two patients) improved or normalized in all cases. Hypogonadism (all patients), hypothyroidism (nine patients) and hypocorticism (four patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10-20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumor size. The good results in this study may be related to the continued use of a fixed dose regimen of bromocriptine regardless of the plasma prolactin lowering effect. PMID- 2311022 TI - Guillain-Barre syndrome and idiopathic thrombocytopenic purpura. PMID- 2311023 TI - HTLV-1 associated myelopathy in Chile. PMID- 2311024 TI - Preoperative hypertension does predict post-carotid endarterectomy hypertension. PMID- 2311025 TI - CMA's response to abortion bill. PMID- 2311026 TI - Medical care is not fully portable for Quebecers. PMID- 2311027 TI - "Clawback" on Medicare benefits: solution to underfunding? PMID- 2311028 TI - The AMA looks north with fear and loathing. PMID- 2311029 TI - Ontario cholesterol controversy. PMID- 2311030 TI - Potential traps for the allergic. PMID- 2311032 TI - Hazard of yawning. PMID- 2311031 TI - The case against HIV antibody testing of refugees and immigrants. PMID- 2311033 TI - "Psychosomatic surgery". PMID- 2311034 TI - AIDS surveillance in Canada. PMID- 2311035 TI - Do health service organizations and community health centres have higher disease prevention and health promotion levels than fee-for-service practices? AB - We interviewed health care providers representing 23 fee-for-service (FFS) practices, 19 health service organizations (HSOs) and 11 community health centres (CHCs) in Ontario to compare self-reported approaches to disease prevention and health promotion. Few significant differences were found across practice types in the presence of recall systems for screening or in knowledge of, compliance with or estimated coverage for selected preventive maneuvers recommended by the Canadian Task Force on the Periodic Health Examination. CHCs reported a significantly greater variety of formal health promotion programs and a greater tendency to use nonphysician health care personnel to carry out both prevention and health promotion activities. The results must be interpreted with caution because of the use of self-reported data, the low response rate for FFS practices and the use of a restrictive definition of disease prevention tied to evidence from the reports of the task force. Thus, the results cast some doubt on the common assumption that increasing the population served by alternative modes of delivery such as HSOs and CHCs necessarily increases the level of disease prevention and health promotion activity. PMID- 2311036 TI - Hemoglobin CHarlem (Georgetown) trait in British Columbia. PMID- 2311037 TI - Endothelial repair. PMID- 2311039 TI - Pharmacists and tobacco: dollars before duty. PMID- 2311038 TI - The Ottawa Heart Institute: it's good, but can we afford it? PMID- 2311040 TI - Seat-belt exemptions: "just say no", experts tell MDs. PMID- 2311041 TI - Separation and divorce and MDs: what is your licence to practise worth? PMID- 2311042 TI - Another day on call. PMID- 2311043 TI - Homicide in the workplace in Ontario: occupations at risk and limitations of existing data sources. AB - This study has identified workplace homicides in Ontario from 1975 to 1985, described those at risk, and examined what existing data sources are most suitable for locating the occurrence of these events. Homicides were identified from two sources: the Office of the Chief Coroner and the Ontario Mortality Database (OMDB). Of the 84 homicides identified, 87% occurred among males; the average annual work-related homicide rate was 0.17 per 100,000 workers, with a male-to-female ratio of 5.2:1. The rates in males were about one-eighth of those reported in California and Texas. The highest rates occurred among policemen, gas station attendants, security guards, and taxi drivers, and in restaurants and in certain retail operations such as jewelry stores. These homicides represented about 4% of all traumatic workplace fatalities. Firearms were responsible for 56% of these homicides and the motive was robbery in 50%. The OMDB proved to be an awkward source from which to identify such deaths because there is no "injury-at work" field on death certificates. Other existing sources of data were not able to locate work-related homicides. Guidelines to protect those at high risk of assault and homicide should be developed. PMID- 2311044 TI - Career interruptions and hours practiced: comparison between young men and women physicians. AB - This study compares current level of workforce participation and number, type and length of career interruptions since entering medical school reported by young men and women physicians. By 10 years from medical school entry, one third of the women studied had taken a maternity/child care leave and 24% had taken time away from their careers for other reasons while only 11% of men had interrupted their careers. The average time taken and reasons given for non-maternity-related career interruption were similar for men and women. Both men and women in the types of medical careers that historically have attracted more women work shorter hours than those in medical career types where women are under-represented. Across career types, women worked shorter hours per week than men and the presence of children further reduced hours of work for women only. Although the women studied are more active professionally than previous generations during their childbearing/rearing years, a considerable gap in the participation level remains. PMID- 2311045 TI - A three-year census of dependent elderly. AB - One attempt to limit the rising health care cost for the expanding elderly population has been to control institutional utilization through community care programs. Evaluative research in this field has focussed on comparing community programs to institutionalization, rather than a simpler and more relevant examination of prevailing patterns of care. This latter approach is important for several reasons: it allows one to examine the effects of new programs; to predict future service needs; to evaluate effectiveness and appropriateness of current patterns of care; and it provides the basis for a co-ordinated approach to planning and policy. For the past three years, all institutions and community agencies in Calgary that provide care to the elderly have co-operated in an annual census to determine the location and services received by each person over 65. Study findings suggest directions for future policy and planning, and raise questions for future research. PMID- 2311046 TI - [Primary care in Quebec: a comparison between private practitioners and physicians working in public community health centers]. AB - Since the early 1970s, there have been two primary care networks in Quebec: the traditional one characterized by fee-for-service; and the public one regrouping 10% of physicians and characterized by a salaried practice within publicly funded local institutions known as CLSCs. Using 1984 data collected on 616 Quebec generalists, 333 in private practice and 283 in CLSCs, we compared the physicians' profile in both networks. In contrast to their colleagues in private practice, CLSC physicians were younger, more often female and more involved in rural practice as well as in community health. They also differed in their attitudes and to some extent in their clinical practices. Overall, the study suggests that the introduction of a public primary care network has served to facilitate the emergence of a more comprehensive type of medical practice in the Quebec health care system. PMID- 2311047 TI - Public health and the global environment. PMID- 2311048 TI - A public health deficiency in the HIV literature? PMID- 2311049 TI - Vancouver's needle exchange program. AB - To stem the spread of HIV among intravenous drug users, and between them and their sexual partners and offspring, Vancouver initiated a multifaceted "ways and means" needle exchange program in March of 1989. As of the end of October, over 2,600 users have registered. The needle exchange rate has increased steadily, reaching a peak of 98% in November. Increases have also been noted in the number of regular users, and requests for referral to addition, medical, social and HIV related services. Outreach services, especially using a van, have expanded program availability. Success in terms of clientele response is accredited primarily to the nonjudgemental, nonintrusive approach. The main problems have been the lack of addiction treatment services, financial and personnel constraints created by the large enrollment, and difficulties with Federal/Provincial funding. Funding for evaluation has been requested. PMID- 2311050 TI - AIDS-related knowledge, attitudes and behaviour in injection drug users attending a Toronto treatment facility. AB - Ninety injection drug users (61 males, 29 females) attending the Addiction Research Foundation Clinical Institute completed an anonymous, self-administered questionnaire about their knowledge, attitudes and behaviour regarding Human Immunodeficiency Virus (HIV) infection. Sixty-two percent had used drugs for more than five years; 61% used primarily heroin, 20% cocaine. Needle sharing was common: 76% within 5 years, 37% within the preceding month, although 87% named needle sharing as a risk factor for HIV infection. Current needle sharers could not be distinguished from former sharers on selected demographic, attitudinal or knowledge variables. Twenty percent of respondents had been HIV tested (all negative); 88% reported willingness to be tested. Thirteen percent would consider suicide or resume heavy drug use in response to a positive test; 19% were uncertain about their response. There may be a risk of serious harm to IDUs who are tested in the absence of excellent counselling and support services. PMID- 2311051 TI - Sample sizes for needles in a haystack: the case of HIV seroprevalence surveys. PMID- 2311052 TI - Controlling air pollution: the plan to reduce nitrogen oxides (NOx) and volatile organic compounds (VOCs) emissions in Canada. PMID- 2311053 TI - An analysis of death ascertainment and follow-up through statistics Canada's Mortality Data Base system. AB - The Canadian Mortality Data Base (MDB) was utilized in mortality follow-up of 17,446 refinery and petrochemical workers throughout Canada. The performance of the system in detecting 757 previously known deaths was evaluated. Of the deaths submitted, 93.1% (90% confidence interval (CI) 91.5-94.5) were detected, including 97.6% (90% CI 96.5-98.4) of deaths which occurred in Canada. Detection was generally unaffected by age, year of death (1964-1973), and the presence of middle initial or the remainder of first name. Slightly lower ascertainment was found for deaths occurring in Quebec (94.5%) and Newfoundland (93.3%). This could be due to several factors, including fewer MDB records with complete identifier information for these provinces, or lower accuracy of linking fields for records supplied to the Agency. Few links were made to employees presumed to be alive, indicating 99.8% specificity for these records. PMID- 2311054 TI - Evaluation of the ATS respiratory diseases questionnaire among French-speaking silicon carbide workers. AB - The American Thoracic Society (ATS) respiratory disease questionnaire for adults was translated by two fluently bilingual Quebec health professionals into simple, everyday French easily understood by an adult population of varying age and educational background. After independent assessment by professional translators, it was field-tested on 165 silicon carbide production workers. Responses to the ATS cough questions were significantly related to those obtained by a semiquantitative estimate of cough frequency. ATS questions on cough and phlegm were significantly associated with the physical sign of productive cough on request. A significant association was found between answers to questions on mild or moderate breathlessness and self-evaluation of breathing on a linear scale. Workers with cough, wheeze, or breathlessness had significantly lower percent predicted FEV1, and FEV1 decreased as the severity of breathlessness increased. Highly significant, dose-dependent associations with current cigarette smoking habit were found for cough, phlegm and wheeze. Significant, dose-dependent associations with phlegm, wheeze and mild breathlessness also occurred with exposure to sulfur dioxide. All of these relationships are similar to findings from studies of English-speaking populations. Minor problems with the original English ATS questionnaire were discovered on translation, and suggestions for improvements were made. Preliminary experience with this French translation suggests that it is a useful, comparable version of the English ATS questionnaire. PMID- 2311055 TI - What "miracle in the making"? PMID- 2311056 TI - Pregnancy outreach program in British Columbia: the prevention of alcohol-related birth defects. PMID- 2311057 TI - Child and youth accidents in northern native communities. PMID- 2311058 TI - Intravenous drug use and hepatitis A: an investigation of an outbreak. PMID- 2311059 TI - In favour of Canadian schools of public health. PMID- 2311060 TI - Tamoxifen for breast cancer: associated endometrial cancer. PMID- 2311061 TI - A phase II study of the combination of etoposide and cisplatin in the therapy of advanced gastric cancer. AB - Forty-eight patients with advanced gastric cancer and measurable areas of malignant disease were treated with etoposide (130 mg/m2/day X 3 days) plus cisplatin (45 mg/m2day on days 2 and 3). Both drugs were given by constant intravenous infusion and repeated every 4 weeks. Common toxic reactions included nausea, vomiting, diarrhea, alopecia, peripheral neuropathy, leukopenia, and thrombocytopenia. Most patients experienced severe but reversible toxic reactions. In 46 evaluable patients an overall objective regression rate of 28% was obtained with a median duration of regression of 4 months. Regression rates were only modestly reduced among patients with prior chemotherapy exposure (21%). Whereas this combination of etoposide and cisplatin does not appear to offer any major advantage over other single and combination regimens in the treatment of advanced gastric cancer, it shows definite activity and its lack of cross resistance with other commonly used agents for this disease could indicate a possible role in new combination or sequential chemotherapy approaches. As an interesting sidelight, we found that 21% of our patients had elevated human chorionic gonadotropin (HCG) levels, and among this group regression rates were higher than in HCG-negative patients. It would be of interest to extend these observations in other gastric carcinoma studies involving cisplatin regimens. PMID- 2311062 TI - Metastatic epidural spinal cord compression. Results of treatment and survival. AB - All medical records of patients treated for metastatic compression of the spinal cord or cauda equina in the eastern part of Denmark from 1979 through 1985 were reviewed. With regard to treatment response and survival, 345 patients could be evaluated. Carcinoma of the lung (19%), prostate (18%), breast (13%), and kidney (10%) were the most frequent primary malignancies causing spinal compression. The outcome of treatment depended primarily on the patients' condition at the time of diagnosis: 79% of the patients who were able to walk before the treatment remained ambulatory, whereas only 21% of the nonambulatory paraplegic patients and 6% of the paralytic patients regained walking ability. Patients treated with laminectomy followed by radiotherapy seemed to respond better than patients treated with radiotherapy or laminectomy alone, but when the patients' pretreatment motor function was taken into account no significant difference was found between the three forms of treatment. In the subgroup of nonambulatory patients, however, a significantly better restoration of gait was observed in patients treated with the combination of laminectomy and radiotherapy than in patients treated with radiotherapy alone. A longer survival in the group treated with the combination of laminectomy and radiotherapy may reflect that these patients were in a lower stage of disease and thus had a better potential of regaining motor function. The results call for prospective randomized studies. PMID- 2311063 TI - Survival rates in patients with differentiated thyroid carcinoma. Influence of postoperative external radiotherapy. AB - Nine hundred thirty-two patients with papillary and follicular thyroid carcinomas were seen at the Departments of Medicine, Surgery, and Radiology of the University of Essen, Essen, Germany, between 1970 and 1986. In addition to standard treatment by surgery, radioactive iodine and medical thyroid stimulating hormone (TSH) suppression, 346 patients had received conventional external irradiation to the neck (mostly 40-60 Gy) before referral to our institutions, whereas 586 patients had not received radiotherapy. From the follow-up data of these patients, survival rates were calculated separately for tumor Stages T1 (n = 203), T2 (n = 552), and T3/T4 (n = 277) using life-table analysis. Distribution of risk factors (histologic type of tumor, grading of malignancy, presence of distant metastases, age and sex) was similar in all groups with the one exception, that the radiotherapy patients with Stage T3/T4 were older. There was no significant difference in the life expectancy of irradiated and not irradiated patients by Breslow and Mantel-Cox tests. In Stages T1, T2, and T3/T4, 75% of the radiotherapy patients survived for 10.6 +/- 0.32, 11.5 +/- 0.61, and 6.71 +/- 0.85 years, respectively; the figures for the nonirradiated patients were 9.4 +/- 0.17, 10.8 +/- 0.37, and 6.26 +/- 0.51 years, respectively. When survival rates were calculated separately for patients with Stage T3/T4 older and younger than 40 years, there was no obvious effect of radiotherapy in the younger group, whereas in the older patients, improvement of survival by radiation just failed to reach statistical significance (P less than 0.09). In conclusion, this retrospective analysis failed to prove that survival is prolonged in patients with differentiated carcinoma by administration of conventional external radiotherapy after surgery. A benefit to older patients with locally advanced tumors has still to be demonstrated. PMID- 2311064 TI - Increased incidence of hypersensitivity to iodine-containing radiographic contrast media after interleukin-2 administration. AB - Eight of 28 (28%) cancer patients with liver metastases treated by either splenic (four) or hepatic (four) arterial infusion of recombinant interleukin-2 (rIL-2) developed hypersensitivity reactions to iodine-containing radiographic contrast media. These reactions consisted of fever, chills, malaise, nausea and vomiting, skin rash, diarrhea, and occasionally, hypotension. Reactions usually occurred 1 month after the initial arteriographic procedure and rIL-2 infusion, with 1-hour to 4-hour intervals between procedure and reexposure of the patient to the iodine containing contrast medium (used in conjunction with computerized tomography or repeated arteriography for subsequent courses of rIL-2 infusions) and the onset of symptoms. Prompt administration of corticosteroids during the reaction and premedication of patients who were known to have had a reaction in the past were very effective in stopping reactions or preventing them from reoccurring. The high incidence (28%) of hypersensitivity reactions, the temporal relationship (4 hours) between the arteriographic procedure (utilizing iodine-containing contrast medium) and the initial infusion of rIL-2 (while some of the contrast medium was still present), and the absence of such hypersensitivity reactions among patients receiving systemic (intravenous) rIL-2 (not requiring the use of concomitant iodine-containing contrast medium) provide additional evidence that in the presence of a potentially immunogenic moiety, rIL-2, a potent stimulant of the human immune system, can produce an initial sensitization followed by subsequent anamnestic reaction upon reexposure of the patient to the immunogen (even without the additional rIL-2). PMID- 2311065 TI - Blastic transformation in essential thrombocythemia. In vitro differentiation of blast cells into granulocytic, erythroid, and megakaryocytic lineages. AB - A 57-year-old man with essential thrombocythemia (ET) developed myelofibrosis, that progressed to a blastic transformation state. The characteristics of the blastic cells were serially studied both morphologically and phenotypically as well as in cell culture. The blastic cells that were first detected in peripheral blood had features of myeloid stem cells with slight differentiation toward megakaryocytic lineage. However, later in the course, most of the blastic cells were immature. During culture in the presence of human plasma-derived serum (PDS), some blastic cells obtained at the initial stage differentiated, mainly to both granulocytes and macrophages morphologically, but later tended to differentiate into both megakaryocytes and macrophages. Finally the blasts appeared to have lost their ability to differentiate morphologically. However, the blasts formed mixed colonies consisting of erythroblasts, granulocytes, macrophages, and immature blasts when cultured in methylcellulose with PHA leukocyte conditioned medium. In addition, the blastic cells in suspension culture strongly expressed phenotypic features which are characteristic of erythroblasts, in the presence of both PDS and 12-0-tetradecanoylphorbol 13 acetate (TPA), whereas they expressed features of megakaryoblasts in the presence of PDS alone. These results suggest that essential thrombocythemia is of myeloid stem cell origin. This is the first case in the literature in which a clonal evolution in ET has been followed closely, essential events were identified serially, and the blastic cells, which appeared as a result of the progression of ET, were found to have the capability to differentiate toward the three myeloid lineages. PMID- 2311066 TI - Evaluation of squamous cell carcinoma antigen as a new marker for lung cancer. AB - Carcinoembryonic antigen (CEA) is the only tumor marker of proven, although limited, value for the management of patients with non-small cell lung cancer (NSCLC). The authors have prospectively assessed the potential value of a new tumor marker, squamous cell carcinoma antigen (SCC Ag), in a large series of patients with advanced lung cancer (LC). Squamous cell carcinoma antigen and CEA levels were measured in 382 healthy persons (N1 group), 90 patients with benign pulmonary diseases, and 291 patients with LC (129 with SCLC and 162 with NSCLC, including 96 with squamous LC). Carcinoembryonic antigen levels were higher in smokers than in nonsmokers, but smoking habits did not influence the serum concentrations of SCC Ag. Elevated values (above the 95th percentiles of N1, i.e., 7.5 ng/ml for CEA and 3.0 ng/ml for SCC Ag) were observed in 11.1% of patients with benign pulmonary diseases for both markers. Carcinoembryonic antigen was more sensitive than SCC Ag, even for squamous LC (56% versus 35% of elevated values, P less than 0.01). The specificity toward squamous LC was better, however, for SCC Ag, for which levels were elevated in only 8.5% of SCLC and in 18% of other forms of NSCLC, compared with 49% and 55%, respectively, for CEA. Moreover, measurement of SCC Ag and CEA levels did not give redundant information: thus, in squamous LC and SCC Ag level was elevated in 32% of the patients with a normal CEA level, increasing from 57% to 71% the proportion of patients with at least one elevated marker. Lastly, elevation of CEA or SCC Ag levels was an adverse prognostic factor in squamous LC (P = 0.05 for CEA; P = 0.07 for SCC Ag). In conclusion, SCC Ag appears to be worthwhile of further investigation in squamous LC. The authors found that this new marker provided additional information on CEA and that it was more specific for squamous LC than CEA. PMID- 2311067 TI - Usefulness of a new tumor marker, Span-1, for the diagnosis of pancreatic cancer. AB - Levels of serum Span-1, a new tumor marker for pancreatic cancer, were assayed in 64 patients with pancreatic cancer, 90 with nonpancreatic cancer, and 254 with nonmalignancies, involving 55 healthy controls. Furthermore, Span-1 was compared with other tumor markers (CA19-9, carcinoembryonic antigen [CEA], and DU-PAN-2). Frequency of elevated Span-1 levels was 81.3% in pancreatic cancer. False positive elevations of serum Span-1 levels were rather common in liver cirrhosis (53.8%) and chronic hepatitis (26.3%). The sensitivity, specificity, and efficiency of this assay for pancreatic cancer, was 81.3%, 75.6%, and 76.5% against all subjects without pancreatic cancer, respectively. In comparison with other markers, sensitivity of Span-1 tended to be highest with similar specificity to those of CA19-9 and CEA. The Span-1 assay has a high sensitivity and specificity for pancreatic cancer. It is almost equivalent to CA19-9 assay. However, this assay is not specific for chronic liver diseases. PMID- 2311068 TI - Results of a screening program for C-cell disease (medullary thyroid cancer and C cell hyperplasia). AB - In the authors' Medullary Screening Clinic, medullary thyroid cancer (MTC) or C cell hyperplasia (CCH) has been identified in 26 relatives of 12 apparently "sporadic" patients from 56 families in which calcitonin (CT) testing has been performed. The interpretation of stimulated test results was sometimes difficult: elevated basal levels without a significant increase after the injection of secretagogues; basal levels in the normal range with considerable increases after stimulation but not exceeding two or three times the upper limit of normal; elevated basal or stimulated CT levels that slowly decreased to normal or near normal levels over relatively short periods of time. The latter results suggest the possibility of CCH disappearing spontaneously in some patients. PMID- 2311069 TI - Is DNA ploidy an independent prognostic indicator in infiltrative node-negative breast adenocarcinoma? AB - To evaluate DNA content as an independent, long-term prognostic indicator in infiltrative, node-negative adenocarcinoma of the breast, flow cytometric DNA analyses were performed retrospectively in 165 patients. The exclusive use of paraffin-embedded tissue permitted the study of patients for whom 3 to 15 years' follow-up was available. Other investigators have shown a relationship between DNA nuclear content and well-known prognostic indicators of breast carcinoma, such as estrogen receptors, age, menopausal status, and stage of tumor. However, very few of these studies were based on patients with long-term clinical follow up and investigated the independent prognostic value of DNA nuclear content. The frequency of aneuploidy in the patients in this study was 57%, with DNA indices ranging from 0.73 to 2.59. Survival in patients with localized breast carcinoma with DNA aneuploid tumors was 84.1% at 5 years and 75.5% at 10 years. Those with diploid tumors showed survival of 87.8% at 5 years and 73.4% at 10 years. These data show no independent prognostic value for DNA nuclear content. The relationship between DNA content, tumor histologic type, and age was also investigated. High-grade tumors were more often aneuploid. There was no association between DNA content and age. Of 165 patients, information regarding estrogen receptor status was available in only 77; 45% of those with aneuploid tumors and 35% with diploid tumors were estrogen receptor-negative. This difference was not significant. The authors conclude that simple determination of DNA ploidy fails to indicate prognosis for infiltrative, node-negative breast carcinoma. PMID- 2311070 TI - Hematogenous metastases to the stomach. A review of 67 cases. AB - Metastatic tumors to the mucosa of the stomach are unusual occurrences that can cause clinical and pathologic problems in diagnosis. The authors report 67 cases from the files of the Veterans Administration Center at Houston. Ten cases were found on endoscopic biopsy and 57 at necropsy. Each patient endoscopically evaluated presented with upper gastrointestinal tract symptoms, including bleeding, abdominal pain, anorexia, and vomiting. At endoscopic examination, characteristic "volcano-like" ulcers were noted. Clinical gastrointestinal symptoms were present in 30 of the necropsy cases, and in four cases the gastric metastases led to the patients' deaths. Tumors primary in the lung accounted for most of the metastases (55%), followed by other gastrointestinal malignancies. A correct diagnosis is important to direct therapy and is facilitated by the characteristic clinical, endoscopic, and histologic findings. PMID- 2311071 TI - The epidermal growth factor receptor and the prognosis of bladder cancer. AB - Epidermal growth factor is found in high concentrations in urine, and its receptor (EGFr) has been identified in certain bladder tumors. This study was performed to determine whether receptor positivity in the tumor was associated with a poor clinical outcome. One hundred one patients with newly diagnosed bladder cancer were studied prospectively by immunohistochemical staining for the EGFr. There were 76 men and 25 women, with a mean follow-up of 30 months; 49 had tumors invading muscle: 18 were pTl (tumor invading lamina propia) and 34 were pTa (tumor confined to urothelium). Strong staining for the EGFr was found in 48% of tumors and was associated with high stage (P less than 0.001). Death of bladder cancer (40 of 101) was associated independently with high stage (P less than 0.0001) and EGFr positivity (P less than 0.001). In patients with pTa and pTl tumors, EGFr positivity was associated with multiplicity (P less than 0.01), time to recurrence (P less than 0.03), and recurrence rate (P less than 0.004). Tumor progression was associated with EGFr positivity (P less than 0.0001) and multiplicity (P less than 0.05). EGFr were found on a significant proportion of bladder tumors: such tumors were more likely to result in death, recurrence, and progression. PMID- 2311072 TI - Inflammatory myofibrohistiocytic proliferation simulating sarcoma in children. AB - The term "inflammatory myofibrohistiocytic proliferation" (IMP) has been proposed to replace the conventional designations of plasma cell granuloma and inflammatory pseudotumor. Three cases of extrapulmonary IMP in children are reported, including an intracerebral lesion which has been formerly undescribed. In children, IMP may be associated with microcytic hypochromic anemia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. In this clinical setting, differentiation of a rapidly growing but benign IMP from a bona fide sarcoma is of paramount importance. PMID- 2311073 TI - Survival of the older patient compared with the younger patient with Hodgkin's disease. Influence of histologic type, staging, and treatment. AB - Age as an independent risk factor for survival of Hodgkin's disease (HD) was investigated using data for the 6345 patients in the American College of Surgeons, Patterns of Care Study. Patients were divided into those 15 to 34 years of age, and those older than 50 years. Older patients had higher rates of advanced stage and B symptoms (e.g., Stage IVB, 19.7% compared with 7.7%) and significantly higher rates of poor prognosis histologic types, odds ratio (OR) = 3.7. The older population with clinical stage (CS) I and II disease was also less likely to have received any of the selected staging procedures, bone marrow biopsy, lymphogram, or laparotomy (OR = 4.48). The two populations were equivalently understaged when CS was compared with pathologic stage (PS). In each category the older patients were more likely to have received no therapy; for PS I and II disease the OR for older patients compared with the younger patient was 2.14. When stratified by PS, B symptom status, histologic type, and treatment the older patients continued to show poorer 5-year survival by the life-table method. The authors' hypothesis--that older patients equivalently staged and treated would have no significant difference in long-term survival--was not substantiated by the data. However, in the analyses in which corrections for the known risk factors were made, the difference in survival was not as great as that in the crude, unstratified data. This study, as well as other recent studies utilizing smaller numbers of patients, finds age an independent predictor of poorer survival in HD patients. PMID- 2311074 TI - Epidemiology of cancer among Hispanic males. The experience in Florida. AB - To assess cancer incidence among Hispanic males in Dade County, Florida, data were analyzed from the statewide tumor registry. For all cancer sites (combined), the age standardized rate among Hispanic males was 308.75 cases per 100,000 person-years, compared with 349.55 among non-Hispanics (standardized rate ratio [SRR] = 0.88; 95% confidence interval [CI] = 0.84-0.93). Hispanics experienced significantly greater rates of cancers of the larynx (SRR = 1.58; 1.19-2.09), thyroid (SRR = 3.12; 1.18-8.26), and gallbladder (SRR = 5.45; 1.55-19.15), compared with non-Hispanics, but significantly lower rates of testicular cancer (SRR = 0.17; 0.09-0.37), melanoma (SRR = 0.20; 0.12-0.34), esophagus (SRR = 0.52; 0.49-0.55), stomach (SRR = 0.61; 0.43-0.87), pancreas (SRR = 0.65; 0.45-0.94), kidney and renal pelvis (SRR = 0.68; 0.48-0.97), colon (SRR = 0.79; 0.67-0.94), lung (SRR = 0.82; 0.73-0.94), and Kaposi's sarcoma (SRR = 0.03; 0.00-0.25). These data suggest that Dade Hispanic males have not experienced the cancers traditionally elevated among US Latinos, or those common among non-Hispanics. PMID- 2311075 TI - Women's attitudes to screening after participation in the National Breast Screening Study. A questionnaire survey. AB - A self-administered questionnaire study exploring women's attitudes to breast screening after participation in the Canadian National Breast Screening Study (NBSS) achieved an 82% response rate. Of active respondents (AR) attending two to five screening examinations, 1582 had received annual mammography (MA) and physical examination (PE) of the breasts and 548 received annual PE alone. Of 139 dropouts after the first screening, 105 received MA and PE and 34 received PE alone. Dropout respondents (DR) were significantly less likely than AR to report receiving very prompt (46% versus 66%), very courteous (73% versus 92%), or very competent examinations (74% versus 95%). Although 35% of those allocated to PE expressed disappointment with PE allocation compared with 9% of those allocated to MA, fewer of those allocated PE were prepared to accept MA in the future than those allocated MA (59% versus 73%). Of those who had MA, 36% reported moderate and 9% extreme discomfort from mammography. Almost half of each subgroup--MA allocations, PE allocations, and DR--preferred mammography every 2 to 3 years and 30% preferred mammography restricted to diagnostic purposes. Only 5% of AR reported anxiety after screening. National Breast Screening Study participation was a positive experience for 93%. An intention to do breast self-examination (BSE) was reported by 89% of AR and 79% of DR. Forgetfulness was a major impediment to BSE. Disincentives for screening were excessive distance to center, painful mammography, fear of radiation, lack of time, and preference for own physician. Convenient location, punctual appointments, and courteous and supportive staff should enhance screening compliance. PMID- 2311076 TI - Random HIV tests. PMID- 2311077 TI - Still no AIDS strategy. PMID- 2311079 TI - Nursing: make it a career. PMID- 2311078 TI - Perceptions of AIDS. PMID- 2311080 TI - Is nursing a semi-profession? PMID- 2311082 TI - Health promotion in the South Pacific. PMID- 2311081 TI - Competency in a changing world. PMID- 2311083 TI - Marketing nursing. PMID- 2311084 TI - Diversional therapy. PMID- 2311085 TI - [Sexually active adolescents]. AB - For today's teenagers, sex education has to go beyond simply handling out information. Young people are becoming sexually active at an earlier age than ever before. Nurses must therefore gear their teaching efforts to individual needs. The author looks at the factors that influence teenage sexual behavior and suggests support in the areas of health, contraception, interpersonal relations and values. The challenge is to arouse teenagers' sense of responsibility. PMID- 2311086 TI - [A nursing process integration project]. AB - An integration experiment conducted at the Regional Hospital of Edmundston, New Brunswick, demonstrates that flexibility and persistence can overcome resistance to this necessary and worthwhile process. Having discovered that overly manipulated data and an inadequate organizational structure can be stumbling blocks to integration, the author shows that support for integration is essential since it can provide a dynamic contribution to the quality of health care. PMID- 2311087 TI - Life & death decisions: the impact on nurses. PMID- 2311088 TI - What children think about hospitals. PMID- 2311089 TI - Aloha clinical rotation in Hawaii. PMID- 2311090 TI - Nursing in paradise. PMID- 2311091 TI - How I spent my summer vacation. PMID- 2311092 TI - [The ventilator]. AB - An information pamphlet that answers common questions about clinical ventilation has helped to alleviate the anxiety felt by relatives of ventilated patients. Since its publication in the Canadian Critical Care Nursing Journal last summer, the pamphlet has been translated by the Ottawa Civic Hospital for the benefit of francophone readers. PMID- 2311093 TI - [Preparation for surgery]. AB - Pediatric surgery can be a traumatic experience for both parents and children. That's why many children are now released the day of their operation. However, the need for preoperative counselling, reassurance and information is still there. The author explains why and shares the results of a preoperative questionnaire that she developed and implemented in a pediatric unit. The resulting improvement in the quality of care is documented. PMID- 2311094 TI - Experimental obstructive coronary atherosclerosis in the hyperlipidemic hamster. AB - The evolution of coronary atherosclerotic lesions induced by a hyperlipidemic diet was examined in male hamsters subjected for up to 40 weeks to a standard chow supplemented with 3% cholesterol and 15% butter. Control animals were fed standard chow only. Five to seven hamsters were monthly sacrificed and investigated for serum lipids and coronary artery lesions. As compared with control animals, the hamsters fed the fat diet showed a progressive increase in serum cholesterol which reached maximum values up to 17 fold in the 10th month. The serum of the hyperlipidemic hamster examined by agarose electrophoresis, Laurell immunoelectrophoresis and cross-immunoelectrophoresis showed at most a 14 fold increase in low density lipoproteins after 10 months diet. The examination of coronary arteries revealed morphologic changes already detectable at 2 weeks of diet. The earliest modifications observed were characterized by proliferation of the subendothelial matrix or/and the appearance of liposome-like structures in the intima. After 2-3 weeks of diet, smooth muscle cells appeared occasionally in the intima and monocytes adhered and penetrated through the endothelium. Later on, smooth muscle cells and macrophage displayed lipid deposits. Focally, in areas of intimal proliferation and foam cells, endothelial cells were also lipid loaded. Like in human atherosclerotic plaque, in the late stages of hamster coronary lesions, there was a progressive accumulation of extracellular unesterified cholesterol, calcium deposition and necrosis. Lesions evolved to a progressive narrowing of the coronary branches affected, with complete obstruction of some small arterial ramifications. Hamster appears to be a suitable model for studying the molecular and cellular events leading to obstructive coronary atherosclerosis. PMID- 2311095 TI - Expression of desmin gene in skeletal and smooth muscle by in situ hybridization using a human desmin gene probe. AB - We have used a probe encoding for the human desmin gene to study the expression of the desmin gene in skeletal and smooth muscle by in situ hybridization. In human skeletal muscle, the results showed a strong and homogeneous level of desmin mRNA contrasting with the faintly immunostaining of the desmin protein. In smooth muscle cells of colon and uterus, in situ hybridization and immunofluorescence staining suggests that there are some cells which do not contain desmin. The optimal condition of desmin mRNA detection was in cryostat sections fixed with paraformaldehyde and in paraffin embedded tissue with the same fixative. The human desmin probe can be used as a marker of cell differentiation and a way to study the regulation of the expression of the desmin gene in pathological events. PMID- 2311096 TI - Surface and membrane morphology of Bergmann glial cells and their topographic relationships in the cerebellar molecular layer. AB - The cerebellar Bergmann glial cells of Swiss albino mouse, teleost fish and human have been examined by means of freeze-fracture and ethanol-cryofracturing techniques for scanning electron microscopy and freeze-etching and thin sectioning techniques for transmission electron microscopy in order to study the outer surface, membrane morphology and topographic relationship with Purkinje cells, parallel and climbing fibers and stellate axons. Freeze-fracture and ethanol-cryofracturing techniques exposed the somatic outer surface and lamellated processes surrounding the Purkinje cells. Transmission electron microscopy showed a granular substance filling the extracellular space separating Bergmann glial cell cytoplasm from dark Purkinje cells. This substance was absent in the vicinity of clear Purkinje cells. Freeze-etching replicas showed a multilayered ensheathment of Bergmann glial lamellar processes surrounding parallel fibers. The P face of Bergmann glial cell plasma membrane exhibited orthogonal arrays or assemblies of intramembrane particles (IMPs) and high density distribution of round IMPs 6-15 nm in diameter, whereas the E face was characterized by a smooth surface and low density distribution of IMPs. Rod intramembrane particles, 20-30 nm in length, were also found in the plasma membrane P and E faces. The fractured Bergmann glial cell cytoplasm was observed encapsulating the parallel fiber varicosities, or the bundles of non-synaptic segments of parallel fibers and enclosing the climbing fiber and stellate axonal synapses with Purkinje dendrites. PMID- 2311097 TI - Endocytosis of serum albumin-gold conjugates by microvascular endothelial cells in rat adrenal gland: regional differences between cortex and medulla. AB - We investigated the distribution of serum albumin (bovine) modified by adsorption to 15 nm diameter colloidal gold (Au15BSA) in rat adrenal vasculature after perfusion of Au15BSA in situ for 6-20 min. A striking difference in permeability to and uptake of Au15BSA by adrenal cortical and medullary endothelial cells was found. The fenestrated capillary endothelial cells in the cortex were permeable to Au15BSA particles, but showed no significant endocytosis of these conjugates. Endothelial cells of the medullary capillaries and venous tributaries of the central vein were markedly less fenestrated than cortical capillaries, and resembled morphologically the sinusoidal endothelial cells of bone marrow. These endothelial cells, unlike those in the cortex, were not permeable to the perfused Au15BSA, and showed endocytosis of the gold-conjugated protein by means of coated pits and vesicles. No evidence of transcytosis of Au15BSA by means of non-coated, plasmalemmal vesicles was found. Uptake of Au15BSA by medullary endothelia was not appreciably diminished by the presence of one hundred-fold excess, unmodified, monomeric BSA. One hundred-fold excess of serum albumin which was modified by treatment with formaldehyde (FmBSA), on the other hand, did effectively compete for uptake of Au15BSA. These results indicate that adrenal medullary endothelial cells, in contrast to those of the cortex, selectively take up serum albumin modified by adsorption to colloidal gold beads, or modified by treatment with formaldehyde. The endocytosis appears to involve selective adsorption of the Au-modified albumin to sites, perhaps receptors, at coated regions of the luminal endothelial surface. PMID- 2311098 TI - Ultrastructure of hybrids derived from electric pulse fusion of human HeLa cells and murine 3T3.4E cells. AB - Somatic cell hybrids were obtained with electric pulse by fusion of human epithelial HeLa cells derived from uterine carcinoma and mouse fibroblasts 3T3.4E, deficient in thymidine kinase. Hybrids were selected and propagated in HAT medium. After 3 passages the cultures were morphologically homogeneous. They retained an epithelial morphology. Electron microscopic and morphometric studies indicate that these hybrids at the 6th passage differed from parental cells. They exhibited the smallest cellular and cytoplasmic size. The number of mitochondria was similar to that of murine fibroblasts but their size was more homogeneously distributed; the mitochondria matrix was more electron dense than in the parental cells. These data suggest that these hybrids have a different metabolism from that of the parental cells; they contained modified mitochondria. PMID- 2311099 TI - Ultrastructural immunolocalization of laminin and fibronectin in human large intestinal mucosa. AB - The ultrastructural expression of laminin and fibronectin was studied in human colonic mucosa with a pre-embedding immunoperoxidase technique. Both antigens were present in epithelial basement membrane. The lamina densa was uniformly and homogeneously immunostained by both fibronectin and laminin, while the lamina rara showed discrete, positive sites occasionally connecting the lamina densa with the epithelial plasma membrane. In the lamina reticularis, fibronectin was diffusely positive, while laminin showed a discontinuous positivity only in the uppermost region in vicinity of the lamina densa. Collagen fibrils were regularly decorated by fibronectin-positive material. Basement membranes in the capillary wall showed a similar pattern of reactivity both with laminin and fibronectin. These results point out that laminin as well as fibronectin are integral components of intestinal mucosa basement membranes. PMID- 2311100 TI - Observations on cardiac ultrastructure of the adult Japanese newt, Cynops pyrrhogaster. AB - Investigation of atrial and ventricular cardiac ultrastructure by transmission and scanning electron microscopy of the adult Japanese newt, Cynops pyrrhogaster, has revealed some unique cell types and features in this amphibian. Typical urodelan-type thin trabeculae composed of myocytes with conventional architecture of loosely scattered myofibrils were observed. Scarce granules of variable size and density were seen in atrial myocytes, and some Purkinje-like fibers were observed. Unique structures included scattered endocrine-like cells with dense cytoplasmic granules in the epicardial spaces, a distinct granular cell found occasionally on the endocardial surface projecting into the lumen of the cardiac trabeculae, and peculiar granulated inclusions in the myoplasm. The function of these possible endocrine cells remains undetermined. It is important to characterize the heart of this species, as it has recently been proven to be an excellent model for prolonged experimental studies in vitro. PMID- 2311101 TI - Specific localization of lectins in boar and bull spermatozoa. AB - The roles that complex carbohydrates play in gamete recognition and fertilization are well-documented. This study was designed to identify and map sites of N linked oligosaccharides in boar and bull sperm. Plant lectins, conjugated with FITC, RITC and gold particles, were used as probes for specific sugar moieties in sperm membranes. Results showed strong labeling of sperm heads by most lectins. However, lectins with specificities for mannosyl, glucosyl, and sialic acid were predominantly distributed over the sperm acrosomal region. Lectins specific for fucosyl residues predominantly stained the postacrosomal regions of both boar and bull sperm. Lectin gold studies revealed that mannosyl and galactosyl-linked residues occupied the acrosomal membrane and plasma membrane in the postacrosomal region, but not the nucleus or nuclear membrane. The cytoplasmic droplet, middle piece and flagellum of boar and bull sperm were moderately stained by lectins. The microquantitative analysis confirmed the fluorescence data. The presence of fucosyl residues predominantly in the postacrosomal regions lends credence to the suggestion that glycoproteins rich in fucosyl-like residues may be a universal carbohydrate moiety involved in recognition processes in mammalian fertilization. PMID- 2311102 TI - Radiation induced changes in the blood capillaries of rat duodenal villi: a corrosion cast, light and transmission electron microscopical study. AB - Disturbances of gastrointestinal function are an important limiting factor in radiotherapy of the abdominal and pelvic regions. The pathogenesis of radiation induced intestinal dysfunction is not completely understood, although the intestinal mucosa has been shown to respond to irradiation by a progressive reduction in villous size. Since blood vessels in other organs have been implicated in the initiation of post-irradiation changes, the present study examines the response of villous blood vessels to an X-ray dose of 10 Gy after 3 days. Vascular corrosion casts and light and transmission electron microscopy (TEM) were used to study the post-irradiation vascular response. In control and sham-irradiated animals, the villous plexus was fountain-like: an arteriole entered the villous base and divided apically into two terminal branches. Villous capillaries apparently derived from the terminal branches, and united to form venules. In capillary loops the vertical inter-capillary distance was greater than the horizontal inter-capillary distance. After irradiation, the vessels became tortuous and the plexus was compressed apico-basally, shown by a decrease in the vertical inter-capillary distance. The capillary luminal diameter, as measured on resin semi-thin sections, was significantly increased. TEM showed that the endothelium was irregular and there was evidence of plasma leakage. These results suggest that villous damage seen after irradiation can include changes in the villous vasculature. PMID- 2311103 TI - Ultrastructural comparative distribution of carbohydrates in human tracheal and frog palate mucosa using neuraminidase and lectin-colloidal gold complexes. AB - We have compared, at the ultrastructural level, the carbohydrate structure of glycoconjugates of the different types of secretory cells of the human tracheal mucosa (HTM) and the frog palate mucosa (FPM), proposed as a model for studying bacterial adherence to mucus-coated respiratory epithelium. In addition to reactivity with Concanavalin A and Lens cullinaris agglutinin, reactivity of Epon embedded HTM and FPM secretory granules was studied by transmission electron microscopy using neuraminidase-gold complex and colloidal gold-adsorbed lectins with affinity for sugar residues of human mucins, namely the following: Helix pomatia, Lotus tetragonolobus, Ricinus communis II, Wheat germ and Limax flavus agglutinins. The affinity of HTM and FPM mucous and serous cells for the different colloidal-gold complexes was very similar, however Limax flavus agglutinin labelled only HTM and not FPM secretory granules. The FPM mucous and serous secretory granules were nevertheless intensely labelled by the neuraminidase-gold complex, demonstrating the presence of sialic acid residues. The close ultrastructural and histochemical similarities between HTM and FPM suggest that the FPM may be a valuable model for studying the specific interaction between microbial lectins and mucus glycoproteins in the bacterial adherence phenomenon. PMID- 2311105 TI - In perspective. PMID- 2311104 TI - Effect of nitrendipine, a calcium antagonist, on the distribution of calcium in aortic smooth muscle cells of deoxycorticosterone-hypertensive rats. A quantitative ultracytochemical study. AB - Rats were made hypertensive by implantation of a pellet of deoxycorticosterone (DOC). A low dose (1 mg/kg twice daily) of the calcium antagonist nitrendipine protects against the increase in total and ionic levels of calcium in the aorta produced by the elevated blood pressure, dissociating at least in part the hypertension from the rise in aortic calcium. Ionic (free) calcium was demonstrated in aortic smooth muscle cells by the pyroantimonate ultra cytochemical method and the electron opaque reaction product quantitated by stereological techniques. As compared to the control group, nitrendipine did not increase the number of vesicles/micron with precipitate located adjacent to the sarcolemma. DOC however increased the number of subsarcolemmal vesicles with electron opaque precipitate and sarcoplasmic calcium. Nitrendipine administration to DOC-treated rats decreased the number of vesicles to that found in the control or nitrendipine-treated group while ionic calcium in the nitrendipine + DOC group was intermediate between the control or nitrendipine group and the DOC group. The total content of calcium measured by atomic absorption correlates with the observations of ionic calcium levels demonstrated ultracytochemically. Aortic dry weights of the DOC and DOC + nitrendipine groups were comparable and significantly greater than those in the control or nitrendipine groups. PMID- 2311106 TI - Nursing knowledge--a Christian perspective. PMID- 2311107 TI - The challenge of change. PMID- 2311108 TI - "Occult" hydrocephalus in children. PMID- 2311109 TI - Surgery of large retrochiasmatic craniopharyngiomas in children. AB - From 1981 to 1988, 24 patients with craniopharyngiomas were operated at the Neurosurgical Clinic of the City Hospital of Hannover. Eleven patients were females and 13 males. The median age was 39 years. Ten patients were 20 years of age or younger at the time of surgery. Among these there were four patients who had large (more than 3 cm in greatest diameter), prevalently retrochiasmatic tumors. They represent 40% of the patients up to 20 years of age. Their age ranged from 8 to 17 years; they were all females. Two patients presented with increased intracranial pressure secondary to hydrocephalus, one patient with decreased vision, and one patient presented with seizures. One patient had been previously operated twice elsewhere. A preoperative shunting procedure was necessary in two patients (in one it was bilateral). All patients were preoperatively evaluated with enhanced and nonenhanced computerized tomography (CT) and with angiography. The major tumor diameter was 4 cm or more in three patients and between 3 and 4 cm in one patient. All tumors were prevalently retrochiasmatic. Three tumors extended to the level of the middle clivus. The tumor was approached subfrontally in two patients and subfrontotemporally in two patients. There was no operative mortality. No patient was neurologically worse postoperatively. All patients required hormonal replacement. Adjuvant therapy was not given. All four patients are clinically and CT recurrence free 5 and 20 months and 3 and 4 years after the surgery. PMID- 2311110 TI - Outcome of craniocerebral trauma in infants and children. AB - The authors examined 927 patients affected by craniocerebral trauma and analyzed the neurological complications that occurred most frequently. The study confirmed that the percentage of craniocerebral trauma, gravity, and complications were different in relation to the sex and age of the patients. Based on this analysis, a correlation was made between the traumatic pathologies and socioeconomic environmental conditions. PMID- 2311111 TI - The risk of intracranial complications in pediatric head injury. Results of multivariate analysis. AB - Retrospective analysis of 12,072 pediatric head injury cases admitted to hospital revealed 159 patients with intracranial complications: 132 had intracranial hematoma and 27 had diffuse brain swelling. Multivariate analysis revealed two risk factors that could be recognized easily by primary-care physicians. They were found to be significant in predicting the development of intracranial complications. These risk factors were impairment of consciousness at the time of admission and clinical and/or radiological skull fracture. Analysis revealed that the combination of impaired consciousness and skull fracture carried the highest risk of complication (75%); however, the presence of impaired consciousness alone had an intermediate level of risk (19%). The presence of skull fracture alone carried a small overall risk (2%); however, this was highly dependent on age. The absence of all the risk factors considered carried a negligible risk of intracranial complications, provided proper skull X-rays were taken and correctly interpreted. PMID- 2311112 TI - Incidence of spinal deformity in children after multiple level laminectomy for selective posterior rhizotomy. AB - Fifty-five children with cerebral palsy had multiple-level laminectomies for selective posterior rhizotomies for the relief of spasticity. They were followed up clinically and radiologically to assess their spinal stability and the possible development of post-laminectomy deformity of the spine. The majority of the deformities found were related to cerebral palsy and did not appear to be due to the laminectomy: 16% had scoliosis, 5% kyphosis, 7% lordosis, and 9% spondylolysis/spondylolisthesis. Spondylolysis is the only abnormality that appeared to be more common in this group than in children with cerebral palsy. PMID- 2311113 TI - Technical basis for magnetic resonance images. AB - The spin-echo procedure is the basic technique in a magnetic resonance (MR) study (the magnetization vector is flipped by 90 degrees onto the ortogonal plane to the main magnetic field). Very soon after the MR procedure was developed, it was pointed out how important it is to achieve the needed contrast with shorter repetition times (TRs) to reduce the imaging time. Recently, fast imaging techniques have been introduced (partial flip angles, short TRs, and the lack of 180 degrees radiofrequency pulses to refocus the spins are their main characteristics; the spins are refocused by the application of a gradient reversal technique). These techniques are particularly needed in pediatric neuroradiology, where the examination time must be as short as possible. At present, partial flip-angle techniques are almost completely replacing the conventional spin-echo procedure, but the variations in flip angle could result in a change in contrast. For these reasons, conventional spin-echo techniques may still be useful in a routine MR study. PMID- 2311114 TI - Cerebrospinal fluid shunt malfunction signaled by new or recurrent seizures. AB - We have observed two patient groups with seizure activity as the primary presentation of shunt malfunction. Eight patients had a first-time seizure, and seven patients had a history of prior seizures, none more recently than 1 year prior to the seizure recurrence. Five of seven patients with prior seizures who seized were on anticonvulsant medication, three of these seven patients had therapeutic anticonvulsant levels. Shunt malfunction was diagnosed via a combination of tests. The electroencephalograms of nine patients were diffusely abnormal with regions of slowing and focal spike activity. Seizure activity stopped in all patients after preoperative stabilization with anticonvulsant medication and shunt revision. These 15 patients represent 2% of all patients treated for shunt malfunction during a 3-year period. The assessment of new or recurrent seizure activity in a previously stable shunted patient should include evaluation of shunt function whatever the anticonvulsant levels. PMID- 2311115 TI - Slit ventricle syndrome after cyst-peritoneal shunting for the treatment of intracranial arachnoid cyst. AB - Serious complications following installation of a cyst-peritoneal shunt in an 8 year-old boy with asymptomatic arachnoid cyst in the middle cranial fossa are reported. Highly elevated intracranial pressure without association of ventriculomegaly seen in this patient indicates slit ventricle syndrome caused by malfunction of the cyst-peritoneal shunt. This phenomenon is worth recognizing as a possible consequence of cyst-peritoneal shunting for the treatment of intracranial arachnoid cyst. PMID- 2311116 TI - Intraoperative subdural hematoma in a patient with arachnoid cyst in the middle cranial fossa. AB - A case of arachnoid cyst in the middle cranial fossa complicated by intraoperative subdural hemorrhage is presented. Accumulation of cerebrospinal fluid (CSF) outside the outer wall of the arachnoid cyst was found to induce the rupture of well-developed, fragile leptomeningeal vessels at the base of the middle cranial fossa. This phenomenon is noteworthy as a pitfall in surgery for intracranial arachnoid cyst and suggests the bleeding source of subdural hematoma occasionally associated with this lesion. PMID- 2311117 TI - Lateral frontal encephalocele associated with dysplasia of orbit, eyeball, and eyelid. AB - A case is reported of a right lateral frontal encephalocele without communication with the midline structures and in concurrence with dysplasia of the orbit, eyeball, and eyelid. PMID- 2311118 TI - Potential risk factors for brain tumors in children. An analysis of 200 cases. AB - Two hundred cases of verified brain tumors occurring in patients under 15 years of age were studied in relation to possible etiologic, genetic, and environmental risk factors. They were compared with 100 age-matched patients harboring solid neoplasms outside the nervous system, as well as with 100 normal children. In our study, first-degree relatives of a brain tumor child did not show a higher incidence of either tumors or of epilepsy and strokes as compared with controls. First-born children (46%) with higher birth weights showed a greater tendency to present brain tumors. Dystocia (18.5%), previous miscarriages (18%), and dietary restrictions during pregnancy (3%) were also noted in this study and compared with data in the literature. No evidence of a role of maternal chickenpox and toxoplasmosis could be found. The pharmacological risk also seemed to be minimal. The mother's hormonal profile is deduced from the age at menarche and delivery, as well as from a tendency to miscarriages and complicated pregnancies. With regard to the immunologic aspect, it is worth noting that 15% of the mothers complained of allergies. Live polio vaccine and zoonosis might suggest a possible role of virus-related factors in the oncogenesis of brain tumors in children. Radiation-related risk is possibly present in less than 5% of cases. Parental occupation is not relevant in this series. PMID- 2311119 TI - Effect of Quin-2 on 45Ca2+ uptake mediated by Na+i/Ca2+o exchange and 45Ca2+ efflux in rat brain synaptosomes: a requirement for [Ca2+]i. AB - The Na+/Ca2+ exchanger of squid axons, barnacle muscle and sarcolemma requires micromolar intracellular calcium for activation in the Na+i/Ca2+o exchange mode ('reverse' Na+/Ca2+ exchange). The requirement for [Ca2+]i has been demonstrated with the use of intracellular calcium buffers, such as Quin-2, to inhibit Na+i/Ca2+o exchange. However, the inhibition of Na+i/Ca2+o exchange in mammalian nerve terminals loaded with Quin-2 has not been observed [7], suggesting a lower sensitivity to low [Ca2+]i for this system. In contrast, the results reported herein indicate that 45Ca2+ uptake in synaptosomes through Na+i/Ca2+o exchange is inhibited by Quin-2 much in the same way as it is in the squid, provided that synaptosomes are preincubated in low Ca2+ medium to avoid saturation of Quin-2. Under these conditions, 45Ca2+ efflux via Ca2+i/Ca2+o exchange is also inhibited. Our results indicate that the Na+i/Ca2+o and Ca2+i/Ca2+o modes of the Na+/Ca2+ exchanger from rat brain synaptosomes require intracellular calcium for activation. However, because no clear relationship between the observed [Ca2+]i values and the inhibition of Na+i/Ca2+o exchange has been found, it is suggested that localised submembrane calcium concentrations not detected by the [Ca2+]i probe might regulate the exchanger. PMID- 2311120 TI - S-100b protein regulates aggregation and fusion of cardiolipin vesicles. AB - We have recently shown that S-100b protein interacts with the polar surface of cardiolipin vesicles [6]. This interaction produces changes in the secondary structure of S-100b as well as changes in the structural organization of cardiolipin vesicles. We report here on the effects of S-100b on cardiolipin vesicles as investigated by turbidity, terbium-dipicolinate fluorescence and freeze-fracture. Experiments were carried out in the absence and in the presence of Ca2+. In the absence of Ca2+ (0.1 mM EDTA), S-100b favors the aggregation and fusion of vesicles to some extent. Under these conditions, electron microscope analyses reveal the presence of fused vesicles along with particles similar to those observed in protein reconstituted systems or to lipid particles observed during fusional processes. In the presence of Ca2+, S-100b counteracts the Ca2(+) dependent tendency of vesicles to aggregate and fuse. Under these conditions, bilayer phases along with hexagonal phases can be observed by electron microscopy. The latter effects of S-100b are not due to chelation of Ca2+ because of the relative concentrations of S-100b and Ca2+ under our experimental conditions and since much larger concentrations of EDTA are required to produce the S-100b effects. We propose that the dimeric nature of S-100b plays a major role in these events. In the absence of Ca2+, the S-100b molecules probably cross link adjacent vesicles, one subunit contacting one vesicle and the other subunit contacting another vesicle through electrostatic bonds. In the presence of Ca2+, due to the large changes occurring in the conformation of the protein (which loses about 52% of its alpha-helical content), S-100b associates strongly with the polar surface of individual vesicles, thus generating some kind of physical barrier to aggregation and fusion of vesicles. PMID- 2311121 TI - Ethanol protects the heart against the calcium paradox injury. AB - Rat hearts were depleted of Ca2+ (less than 10(-9) M) for 10 min, followed by 15 min of Ca2+-repletion. The calcium paradox injury occurs during Ca2+-repletion, after a period of calcium depletion. The calcium paradox injury was assessed by percent recovery (hemodynamics, [Ca2+]i, and energy levels) during Ca2+ repletion. A decrease in Na+ concentration during Ca2(+)-depletion did not allow for recovery during Ca2(+)-repletion, however 2.5% and 5% ethanol during Ca2(+) depletion allowed for an approximate 50% recovery during Ca2(+)-repletion. A combination of ethanol (2.5% or 5%) with a low extracellular Na+ concentration (88 mM) allowed for complete recovery. Ethanol prevented a depletion of diastolic [Ca2+]i during Ca2(+)-depletion, and allowed for a return of normal diastolic [Ca2+]i during Ca2(+)-repletion. Ethanol modulates the activity of the Na+/Ca2+ exchanger and protects against the Ca2(+)-paradox injury. PMID- 2311122 TI - Multiple beta 1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. AB - Mammalian cell receptors that promote entry of intracellular bacteria into nonphagocytic cells have not been identified. We show here that multiple members of the integrin superfamily of cell adhesion receptors bind the Y. pseudotuberculosis invasin protein prior to bacterial penetration into mammalian cells. Affinity chromatography of crude detergent extracts demonstrated that integrins containing the subunit structures alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1 bound to immobilized invasin. Furthermore, phospholipid vesicles containing isolated integrin proteins were able to attach to invasin. Specificity for invasin binding to the identified integrin receptors was also demonstrated, as immunoprobing and phospholipid reconstitution studies showed that the alpha 2 beta 1 integrin, beta 2 chain integrins, and vitronectin receptor (alpha v beta 3) were not involved in cellular attachment to invasin. PMID- 2311123 TI - Induction of tumor cytotoxic immune cells using a protein from the bitter melon (Momordica charantia). AB - The fruit and seeds of the bitter melon (Momordica charantia) have been reported to have anti-leukemic and antiviral activities. This anti-leukemic and antiviral action was associated with an activation of murine lymphocytes. A partially purified protein factor from the bitter melon caused an infiltration and activation of peritoneal exudate cells in C57B1/6J, C3H/HeJ, and C3H/HeN mice. When the extract was injected twice a week at 8 micrograms of protein per ip injection for 0-4 weeks, the peritoneal exudate cells from the treated mice were cytotoxic in a long-term (18-hr) 51Cr-release assay against a range of labeled targets: L1210, P388, and MOLT-4 tumor cells. Cytotoxicity was also observed against YAC-1 targets in a short-term (4-hr) assay. Fractionation of the cytotoxic immune cells implicated a nonadherent cell population which was capable of killing an NK-sensitive cell line in a 4-hr 51Cr-release assay. Unit gravity sedimentation studies indicated that the cytotoxicity was due to either a neutrophil or a large lymphocyte. Antibody depletion experiments using antibody to asialo GM1, an NK cell-specific antibody, depleted cytotoxicity observed in nonadherent, Ficoll/Hypaque-separated PEC. This suggests that at least part of the anti-leukemic activity of the bitter melon extract is due to the activation of NK cells in the host mouse. PMID- 2311124 TI - The effects of genetics and age on expression of MHC class II and CD4 antigens on rat cardiac interstitial dendritic cells. AB - Interstitial dendritic cells (IDC) in normal hearts of inbred rat strains and congenic and congenic recombinant lines were identified and quantitated by immunohistologic methods, on the basis of cellular reactivity with MRC-OX6, a monoclonal antibody (MAb) directed against MHC class II determinants, and with W3/25, a MAb directed against a CD4 epitope. In all strains and lines examined, the W3/25+ IDC frequency was uniformly high with little interstrain variation. In contrast, all rat strains and lines examined showed either high or low OX6+ IDC frequency. Double staining by two color immunofluorescence indicated that strains with a low OX6+ IDC frequency were characterized by a high frequency of W3/25+ OX6- IDC and a low frequency of W3/25+ OX6+ IDC. In strains with high OX6+ IDC frequency, the majority of IDC coexpressed both markers. Comparative analysis of (i) MHC identical background disparate strains and lines, (ii) MHC disparate background identical strains and lines, and (iii) F2 segregation analysis of intercrosses and backcrosses derived from an original cross between high and low frequency OX6+ IDC strains, all indicated that OX6+ IDC frequency is dependent upon both MHC- and non-MHC-linked genetic factors. It is suggested that rat cardiac OX6+ IDC frequency is influenced by a minimum of two autosomal genes, one of which is MHC linked. The frequencies of both W3/25+ IDC frequency reached adult levels by 10 days of age; adult levels of OX6+ IDC were not attained until Day 21. It is postulated that in the rat heart, W3/25+ OX6- IDC are potential precursors of W3/25+ OX6+ IDC, and that the cellular frequency of coexpression in the adult is under genetic influence. Whether these genetic factors modify constitutive or physiologic levels of class II-inducing lymphokine activity, or influence cellular susceptibility of IDC to induced class II expression is unclear. PMID- 2311125 TI - A novel guanosine analog, 7-thia-8-oxoguanosine, enhances macrophage and lymphocyte antibody-dependent cell-mediated cytotoxicity. AB - Intraperitoneal treatment of mice with a novel guanosine analog, 7-thia-8 oxoguanosine (7-thia-8-oxoGuo), gives rise to activated splenic lymphocytes and peritoneal macrophages with enhanced capacity to mediate antibody-dependent cellular cytotoxicity (ADCC). ADCC activities against both chicken red blood cells and P815 murine plasmacytoma cells were enhanced, indicating that macrophages as well as lymphocytes functioning as K-cells in the two distinct cytolytic systems, were activated by 7-thia-8-oxoGuo. Furthermore, 7-thia-8 oxoGuo enhanced lymphocyte-mediated ADCC activity in beige (bgJ/bgJ) mice against P815, thus indicating the ability of 7-thia-8-oxoGuo to function as a potent immunomodulator even in an animal that is known to possess selective impairment of naturally occurring killer lymphocytes. These results suggest that 7-thia-8 oxoGuo could serve as an agent for immunomodulation and immunorestoration. PMID- 2311126 TI - Inhibition by anti-HLA class I mAb of IL-2 and IL-2 receptor synthesis in lymphocytes stimulated with PHA-P. AB - Inhibition by anti-HLA Class I monoclonal antibody (mAb) Q6/64 of phytohemagglutinin (PHA)-P-induced peripheral blood mononuclear cell (PMBC) proliferation is associated with a reduction of Tac expression and interleukin 2 (IL-2) secretion. To analyze the mechanism(s) underlying the latter phenomena, the Tac gene and IL-2 gene transcription was analyzed by a nuclear transcription assay. No synthesis of Tac and IL-2 mRNA was detected in PBMC stimulated with PHA P in the presence of mAb Q6/64. In conjunction with our recently published data, these results indicate that the blocking by anti-HLA Class I mAb of PHA-P-induced PBMC proliferation reflects an inhibitory effect within the signal transduction pathway leading to transcriptional activation of IL-2 and IL-2 receptor genes. PMID- 2311127 TI - In vitro induction of crawling in the amoeboid sperm of the nematode parasite, Ascaris suum. AB - In a highly synchronous process, the immotile spermatids of Ascaris suum extend pseudopods and become rapidly crawling sperm when treated with an extract from the glandular vas deferens of the male under strict anaerobic conditions. Within 9-12 min, a pseudopod develops, elongates rapidly, and exhibits a continuous flow of membrane specializations, the villipodia, from tip toward base. When attached to acid-washed glass, the pseudopod pulls the cell body along at speeds exceeding 70 microns/min. The pseudopod length remains constant while retrograde flow of villipodia proceeds at the same rate as the sperm's forward movement. Cohorts of about 15 villipodia form at the leading edge, move rearward together, and disappear at the junction of pseudopod and cell body. These are the terminations of branched, refringent fibers, which extend the length of the pseudopod. The latter are the fiber complexes that form its cytoskeleton (Sepsenwol et al.: Journal of Cell Biology 108:55-66, 1989). Locomoting cells sometimes change direction when another crawls by and follow each other. When cells are exposed to air, forward movement ceases in a predictable pattern: the forward extension of the leading edge ceases, the pseudopod shortens from the base, and the cell body continues to be pulled forward. These data contribute to a model for Ascaris sperm amoeboid motility in which independent processes of continuous extension at the leading edge and continuous shortening at the base of the pseudopod act to propel the cell forward. PMID- 2311128 TI - Construction of an h+S strain of Schizosaccharomyces pombe. AB - By spontaneous in vivo integration of a mat2:1 degrees plasmid, containing a Plus (P) cassette, into an h-L MT region of Schizosaccharomyces pombe an h+ strain was obtained which neither mutates to h- nor to h90. Southern blotting showed that it possesses the same mating-type (MT) configuration as h-S except that P information resides in both cassettes. Therefore the strain was called h+S. By crossing h+S with the h- strain LK42 of Engelke et al. (1987) it was possible to obtain h- recombinants with the MT configuration mat1:1(M)smt-o-L-mat2:3(P). Because of the totally defective smt signal (smt-o) in these recombinants no MT switching occurs, so that M information is conserved in mat1:1; furthermore the cassette mat2:3(P) is not expressed like in strains with a K region. This proves that the K region does not cause the silencing of mat2:3(P). PMID- 2311129 TI - Nonsense suppressors partially revert the decrease of the mRNA level of a nonsense mutant allele in yeast. AB - suc2 degrees is a naturally occurring amber mutant allele of the yeast invertase structural gene SUC2. Strains carrying suc2 degrees had only 10% of the wild type invertase-specific mRNA level. Amber suppressors, which allowed suc2 degree strains to ferment sucrose caused an increase of the SUC-specific mRNA level. PMID- 2311130 TI - Kinetic studies of the hydrolysis of platinum-DNA complexes by nuclease S1. AB - The antitumor agent cis-diamminedichloroplatinum(II) (cis-DDP) reacts covalently with DNA and disrupts its secondary structure. Damaged DNA, but not native DNA, is readily digested by S1 nuclease, an endonuclease specific for single stranded polynucleotides. We have measured S1 nuclease digestion of platinated DNA by the release of platinum-DNA adducts and compared it with digestion of unplatinated DNA. The rate of hydrolysis of damaged substrate from platinum-DNA complexes was less than the overall rate of digestion of nucleotides. Similar results were observed for platinum-DNA complexes in native, denatured or renatured conformations. The hydrolysis of denatured platinum-DNA complexes, rb = 0.075 platinum per nucleotide, obeyed Michaelis-Menten kinetics. Taking into account the level of DNA damage, Vm, for the release of platinated adducts was 0.6 times smaller than for digestion of unplatinated DNA. Km values and competition experiments indicated that the enzyme bound equally well to platinated and unplatinated substrates. Similar results were obtained for denatured DNA complexes with trans-DDP while [PtCl(diethylenetriamine)]Cl had no influence on nuclease digestion. These results suggest that bifunctional platinum-DNA lesions have contradictory effects on the hydrolysis of double stranded DNA by S1 nuclease. On one hand they create nuclease sensitive substrate by disrupting DNA secondary structure. On the other, they inhibit digestion of the damaged strand by increasing the activation energy for hydrolysis. PMID- 2311131 TI - The effects of inducers of the endoplasmic reticulum, peroxisomes and mitochondria on the amounts and synthesis of ubiquinone in rat liver subcellular membranes. AB - Rats were treated with inducers of peroxisomes, mitochondria and the endoplasmic reticulum, as well as receiving diets and drug known to influence the mevalonate pathway. Treatment with clofibrate and 2-diethylhexylphthalate (DEHP) increased microsomal and mitochondrial ubiquinone contents, but a decrease was observed in lysosomes. In vivo labeling of this lipid with [3H]mevalonate was also elevated. The amount of cholesterol did not change upon exposure to these inducers of peroxisomes and mitochondria, but its rate of labeling was decreased. The concentration of dolichol increased only after treatment with DEHP and only in lysosomes. The inducers of the endoplasmic reticulum phenobarbital, 3 methylcholanthrene and N-nitrosodiethylamine enhanced the rate of ubiquinone synthesis and exposure to the latter two substances also elevated the amount of this lipid in microsomes. A cholesterol-rich diet increased the labeling of ubiquinone and decreased cholesterol labeling, while cholestyramine treatment had opposite effects on lipid labeling in both microsomes and mitochondria. The results demonstrate that the ubiquinone contents of the various membranes of hepatocytes change in a characteristic manner under the influence of inducers and dietary factors. Clearly, the level of ubiquinone and its biosynthesis are regulated separately from those of the other products of the mevalonate pathway, cholesterol and dolichol. PMID- 2311132 TI - Nucleophilic selectivity and reaction kinetics of chloroethylene oxide assessed by the 4-(p-nitrobenzyl)pyridine assay and proton nuclear magnetic resonance spectroscopy. AB - The nucleophilic selectivity (Swain-Scott's constant s) of chloroethylene oxide (CEO), an ultimate carcinogenic metabolite of vinyl chloride, was determined to be 0.71 using the 4-(p-nitrobenzyl)pyridine (NBP) assay (Spears method). The molar extinction coefficient of the adduct formed between NBP and CEO was measured; and the second-order rate constants for the reactions of CEO with NBP and with thiosulfate were estimated at three temperatures. The disappearance of CEO and the formation of chloroacetaldehyde (CAA) and glycolaldehyde (GCA) were followed in D2O or a mixture of D2O/hexadeuterated acetone (acetone-d6), using Fourier transform proton nuclear magnetic resonance spectroscopy (1H-FTNMR). Evidence was obtained that CEO reacts with chloride ions to yield CAA at a rate constant of about 17 M-1 h-1 in D2O/acetone-d6 (1 : 1, v/v) at 280 K. Under the same conditions, the first-order rate constant kr for the thermal rearrangement of CEO into CAA was estimated to be approximately 0.41 h-1. These data suggest that the isomerization of CEO may be a minor reaction in physiological saline. These chemical properties of CEO are discussed in relation to the mechanism of vinyl chloride-induced carcinogenesis. PMID- 2311133 TI - [A new route to supply potassium in patients with cardiac failure]. PMID- 2311134 TI - [Nursing care of myasthenia gravis]. PMID- 2311135 TI - [Nursing care of traumatic disruption of the bronchus tracheal]. PMID- 2311136 TI - [Nursing care of augmentation mammaplasty]. PMID- 2311137 TI - [Methods of feeding and increase in the body weight of neonates]. PMID- 2311138 TI - [Standard quality control of the central supply room]. PMID- 2311139 TI - Solubilization of multilamellar liposomes of egg yolk lecithin by the bile salt sodiumtaurodeoxycholate and the effect of cholesterol--a rapid-ultrafiltration study. AB - The solubilization of multilamellar egg yolk lecithin liposomes by sodiumtaurodeoxycholate in aqueous phase was studied by ultrafiltration as a function of time, bile salt and cholesterol concentration. The corresponding equilibrium states were analysed. Complete solubilization was achieved at total bile salt/lecithin molar mixing ratios of approximately 5. The minimum ratio to start solubilization was 0.1, corresponding to a free bile salt concentration of only 5% of the critical micelle concentration (CMC). Mean equilibrium constants for the partition of bile salts between non-filterable aggregates and filterable mixed micelles and also the free bile salt concentration were determined. Sodiumtaurodeoxycholate had a higher affinity for small mixed micelles than for lamellar mixed aggregates especially in the presence of cholesterol, which reduces the degree and rate of the solubilization process. A non-homogeneous distribution of bile salts in the lipid phase was detected at low bile salt concentrations. PMID- 2311140 TI - Voltage-dependent behaviour of dolichyl phosphate-phosphatidylcholine bilayer lipid membranes. AB - The current-voltage steady-state characteristics, cyclic voltammograms and capacitance-voltage steady-state relationships of bilayer lipid membranes made from dioleoylphosphatidylcholine or its mixtures with dolichyl-12 phosphate have been studied. Sustained fluctuations of the capacitance of dolichyl phosphate modified bilayers under applied voltage were observed. The results suggest that the dynamics of dolichyl phosphate molecules in membranes can be regulated by transmembrane electrical potential. PMID- 2311141 TI - Surfactant partition between bulk water and DPPC vesicle membrane: solid-gel vs. liquid-crystalline membrane. AB - The main phase transition temperature, Tm, of dipalmitoylphosphatidylcholine (DPPC) vesicle membrane was measured in the presence of the cationic surfactants tetradecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide. Variation of the perturbing effect of these surfactants on Tm with the lipid concentration was analyzed according to the theory recently proposed by Kaminoh et al. (Y. Kaminoh, C. Tashiro, H. Kamaya and I. Ueda (1988) Biochim. Biophys. Acta 946, 215-220), and the partition coefficients of the surfactant into solid gel and liquid-crystalline membranes were estimated. PMID- 2311142 TI - Non-linear least squares analysis of phase diagrams for non-ideal binary mixtures of phospholipids. AB - A computer program for non-linear least squares minimization has been applied to construct temperature-composition phase diagrams for several binary systems of different phospholipids based on their calorimetric data. The calculated phase diagram is guided to fit the calorimetric data with two adjustable parameters that describe the non-ideal mixing of lipid components in the gel and liquid crystalline phases. The parameter estimation procedure is presented to show that the computer program can be used not only to generate phase diagrams with characteristic shapes but also to numerically estimate the lipid-lipid pair interactions between the mixed and the like pairs in the two-dimensional plane of the bilayer in both the gel and liquid-crystalline states. The binary lipid systems examined include dimyristoylphosphatidylcholine/1-palmitoyl-2 stearoylphosphatidylchol ine, 1-capryl-2-behenoylphosphatidylcholine/1-behenoyl-2 lauro ylphosphatidylcholine, and 1-stearoyl-2 caprylphosphatidylcholine/dimyristoylphosphatidylchol ine. PMID- 2311143 TI - Amiodarone and anaesthesia. PMID- 2311144 TI - Risk of cross-infection related to the multiple use of disposable syringes. AB - The rate of blood contamination of IV tubings used in anaesthesia practice was investigated. Only IV tubings started in the operating room were studied. First, 300 tubings of three different types were tested at the three distal injection sites. The contamination rate was 3.3 per cent at the injection site closest to the IV catheter and 0.3 per cent at the furthest. The presence of a check-valve did not affect the contamination rate. Second, 300 third injection sites fixed at a level equal to or above the IV catheter were tested. None of them was contaminated. Finally, in order to evaluate whether changing the needle alone could prevent the contamination of syringes, injections were made into a tubing where blood was flowing. Thirty-four per cent of the syringes tested positive for blood. We conclude that IV tubings have a significant contamination rate in usual practice. This rate decreases as the distance from the IV catheter increases. The use of the third site fixed at a level equal to or above the IV catheter carries a lower risk of contamination. Changing the needle alone is a useless procedure to prevent cross-contamination. PMID- 2311145 TI - Epidural epinephrine and the systemic circulation during peripheral vascular surgery. AB - This study was designed to determine the haemodynamic effects of epidural epinephrine, 5 micrograms.ml-1, added to bupivacaine, 0.75 per cent, in elderly patients with cardiac disease undergoing peripheral vascular surgery (PVS). The effect of epidural epinephrine on the plasma concentration of bupivacaine was also measured. Twenty patients with a history and/or ECG evidence of myocardial ischaemia requiring PVS were randomly assigned to two groups. The patients were monitored with a modified V5 ECG, oscillometric BP monitor and a PA catheter. After control haemodynamic measurements, 12 ml of bupivacaine, 0.75 per cent, +/- epinephrine, 5 micrograms.ml-1, was injected over five minutes into the epidural space at L3-4. Supine haemodynamic measurements were repeated at 15 and 45 min after injection. At 15 min after epidural injection, compared with control values, patients receiving epidural epinephrine showed a significantly greater decrease in mean blood pressure and systemic vascular resistance, and a significantly greater increase in cardiac output than patients receiving plain epidural bupivacaine (79.3 +/- 11.6 per cent vs 94.6 +/- 16.8 per cent, 61.6 +/- 9.0 vs 91.6 +/- 19.2 per cent, 130.8 +/- 23 vs 105 +/- 20.8 per cent, respectively). These differences were not present at 45 min after epidural injection. Heart rate was not significantly different between groups at either time. The presence of epidural epinephrine reduced the peak plasma concentration of bupivacaine from 0.86 +/- 0.20 to 0.64 +/- 0.33 micrograms.ml-1 and increased the time to achieve this concentration from 16.1 +/- 11.2 to 33.7 +/- 20.1 min. PMID- 2311146 TI - Plasma lidocaine concentrations during continuous epidural infusion of lidocaine with and without epinephrine. AB - Plasma lidocaine concentrations were measured over a five-hour period in 20 patients following continuous epidural infusion of lidocaine for surgical anaesthesia. Patients were divided into two groups: Group I received plain lidocaine; Group II received lidocaine with epinephrine. Patients initially received 10 ml followed by a constant infusion of 10 ml.hr-1 of two per cent lidocaine. The mean plasma concentrations of lidocaine were significantly higher for the first 40 min in Group I than in Group II. However, from one to five hours, there was no significant difference between the groups. These results demonstrate that the addition of epinephrine to lidocaine does not decrease the plasma concentration of lidocaine during continuous epidural infusion for long operations. PMID- 2311147 TI - Comparative evaluation of propofol and thiopentone for total intravenous anaesthesia. AB - Sixty unpremedicated ASA physical status I or II patients scheduled for surgical procedures of intermediate duration (15 to 60 min) were studied to evaluate the safety and efficacy of propofol, to measure recovery times and to compare the return of psychomotor and cognitive function with thiopentone. Patients were randomly allocated into two groups. Anaesthesia was induced and maintained by either propofol (2.0-2.5 mg.kg-1 followed by a continuous infusion 0.1-0.2 mg.kg 1.min-1) or thiopentone (4.0-5.0 mg.kg-1, and infusion rate 0.16-0.32 mg.kg-1.min 1), titrated to patient response. Succinylcholine was administered to facilitate tracheal intubation and maintain neuromuscular blockade. Induction of anaesthesia was slightly longer with propofol than thiopentone (42.2 vs 29.8 sec) and was smooth with both drugs. Post-intubation increases in heart rate, and systolic and diastolic blood pressures were attenuated by propofol when compared with thiopentone. After the administration of propofol, times to eye opening (6.4 +/- 4.3 vs 13.9 +/- 15.9 min), response to verbal command (7.6 +/- 6.3 vs 15.4 +/- 16.6 min) and orientation (22.7 +/- 12.8 vs 36.2 +/- 23.1 min), were significantly shorter. Psychomotor and cognitive function returned earlier with propofol and fewer side effects were noted. At 24 hr there was no distinguishable difference between groups. Propofol is a safe anaesthetic agent with the potential for early patient discharge and street fitness after outpatient procedures. PMID- 2311148 TI - Preoperative parental anxiety predicts behavioural and emotional responses to induction of anaesthesia in children. AB - Parental presence at induction of anaesthesia is desirable if it makes the child happier and more cooperative. This study evaluated the emotional and behavioural responses of children to being accompanied by a parent at induction of anaesthesia in a paediatric day-care surgical centre. One hundred and thirty-four patients (aged 2-10 yr, ASA physical status I or II) were divided into two groups by day of surgery, to have a parent present at induction of anaesthesia (treatment group), or to be unaccompanied (control group). Before, and at one week after surgery, the child's fears and behaviour were scored by the Hospital Fears Inventory (HFI) and Behavioural Questionnaire (BQ), and parental anxiety by the Parents' Questionnaire (PQ) before and at one week after surgery. The Global Mood Scale (GMS) was used to assess the child's behaviour and the Visual Analogue Scale (VAS) to assess the parent's anxiety on arrival for surgery and at induction of anaesthesia. All patients and parents were disturbed by the experience, but to the same degree in the treatment and control groups. Subgroups of "calm" and "anxious" parents were identified by a median split of their preoperative VAS scores. Children in the "calm-treatment," "calm-control" and "anxious-control" subgroups were similarly upset at induction. Children in the "anxious-treatment" subgroup were the most disturbed at induction, and significantly more than those in the "anxious-control" subgroup. Preoperative parental anxiety levels also correlated with the child's fears and behaviour one week after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311149 TI - Edrophonium priming for antagonism of atracurium neuromuscular blockade. AB - Edrophonium administered in divided doses has been reported to accelerate antagonism of neuromuscular blockade, i.e., a "priming" effect. Since measured onset times can be affected by the type of stimulation used, this effect was studied using both train-of-four (TOF) and single twitch (ST) stimulation. During thiopentone-nitrous oxide-enflurane anaesthesia 20 adults were given atracurium 0.5 mg.kg-1. Both ulnar nerves were stimulated with TOF every 12 sec until one per cent recovery of first twitch (T1). At this time, ST stimulation was applied to one arm, selected at random. When the mean value of T1 and ST reached ten per cent of control, edrophonium, 1 mg.kg-1, preceded by atropine was given either as a single dose, or in two doses consisting of 0.2 mg.kg-1 followed by 0.8 mg.kg-1 three minutes later. No statistically significant differences were observed between T1 and ST for the next ten minutes, whether edrophonium had been given in single or divided doses. Giving edrophonium in divided doses did not improve recovery significantly, measured with either T1, ST or train-of-four ratio (T4/T1). Five minutes after the first administration of edrophonium, T1 was (mean +/- SEM) 86 +/- 3 and 86 +/- 2 per cent control in the single and divided dose groups respectively. Corresponding values for ST were 89 +/- 1 and 89 +/- 2 per cent (NS), and for TOF, 49 +/- 3 and 57 +/- 3 per cent (NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311150 TI - A comparison of the cerebral pressure-flow relationship for halothane and isoflurane at haemodynamically equivalent end-tidal concentrations in the rabbit. AB - The cerebral pressure-flow relationship for halothane and isoflurance was studied at end-tidal concentrations which resulted in similar baseline mean arterial pressure (MAP). Two groups of New Zealand white rabbits (n = 8; each group) were studied with five regional blood flow determinations in each animal. Blood flow was determined by injecting radioactive microspheres during the following conditions: injection 1: after stable 2.05 per cent end-tidal isoflurane (1.0 MAC) Group I; or after stable 0.74 +/- 0.04 per cent end-tidal halothane (0.53 MAC) Group H. Injections 2-5: after MAP was increased 20, 40, 60, and 80 per cent respectively above baseline MAP by phenylephrine infusion. Baseline MAP was the same for both groups (64.3 +/- 3.1 vs 67.2 +/- 2.0 mmHg; mean +/- SEM; Group I and H respectively). Baseline total CBF (tCBF; 0.68 +/- 0.03 vs 0.86 +/- 0.05) and hemispheric CBF (hCBF; 0.64 +/- 0.03 vs 0.96 +/- 0.06) were significantly greater in Group H; no significant difference between groups was seen for baseline posterior fossa CBF (pCBF; 0.79 +/- 0.06 vs 0.75 +/- 0.04). For each experiment a pressure-flow curve was generated by curvilinear regression analysis. Significantly greater phenylephrine concentrations were required for injections 2-5 in Group H. Mean slopes and intercepts were derived for each group. Within each group comparison of the pressure-flow curves for hCBF vs MAP and pCBF vs MAP showed autoregulation was less impaired in posterior fossa structures (cerebellum and brain stem) for both anaesthetic agents (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311151 TI - Spinal tetracaine decreases central nervous system metabolism during somatosensory stimulation in the rat. AB - The influence of spinal tetracaine on central nervous system (CNS) metabolism was determined during nociceptive stimulation. Rats were divided into a halothane group in which the sciatic nerve was stimulated during 0.5 per cent halothane anaesthesia, a tetracaine group in which the sciatic nerve was stimulated during a simultaneous tetracaine spinal and 0.5 per cent halothane anaesthetic, or an awake group. Autoradiographic determination of local spinal cord and cerebral glucose utilization was performed using 14C-2-deoxyglucose. Central nervous system metabolism was greater in the halothane group than the tetracaine and awake groups (P less than 0.05). The only meaningful differences between the tetracaine and awake groups were in two lumbar grey areas at the site of drug administration where metabolism was decreased in the tetracaine/stimulated group. These results indicate that spinal tetracaine effects a decrease in metabolism locally, and attenuates increases in metabolism throughout the CNS observed during somatosensory stimulation. PMID- 2311153 TI - Apnoea and unconsciousness after apparent recovery from alfentanil-supplemented anaesthesia. AB - Several cases of recurrent respiratory depression progressing to apnoea and unconsciousness after apparent recovery from sufentanil have been reported recently. Alfentanil has the shortest elimination half-time of the narcotics used in anaesthesia, suggesting that it should be the least likely to cause postoperative respiratory depression. A case of recurrent unconsciousness and respiratory arrest after apparent recovery from alfentanil-isoflurane-nitrous oxide anaesthesia is reported. A total dose of 137 micrograms.kg-1 alfentanil was given over a 3.25-hr period to a 45-year-old female undergoing partial gastrectomy. Naloxone, 0.16 mg IV, rapidly restored spontaneous ventilation and consciousness. This case demonstrates that apnoea and unconsciousness can also recur after apparent recovery from alfentanil. Recovery room personnel should be aware of this phenomenon. Earlier detection may permit treatment before apnoea occurs. Patients given narcotic-supplemented anaesthesia should be monitored by capnography and/or pulse oximetry in the early postoperative period. PMID- 2311152 TI - Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine. AB - Reversal of opioid effects by naloxone (NX) can lead to significant cardiovascular problems. We have reported previously that hypercapnic dogs develop greater increases in blood pressure and plasma catecholamine (CA) levels than hypocapnic ones when reversed with naloxone. We have also demonstrated differences between NX and nalbuphine (NBPH) in producing excitatory adrenergic responses when administered during normocapnia. The present study was designed to investigate possible dissimilarities in cardiovascular and sympathetic events after administration of either NX or NBPH in dogs made hypercapnic following fentanyl administration. After induction of anaesthesia with thiopentone and intubation, two groups of dogs were maintained with controlled ventilation on enflurane in oxygen anaesthesia and given 50 micrograms.kg-1 fentanyl IV. This caused a significant decrease in heart rate (HR) (P less than 0.001), mean arterial blood pressure (MAP) (P less than 0.001), and plasma concentrations of norepinephrine (NE) (P less than 0.002). Then, ventilation was decreased to produce a PaCO2 of 60 mmHg; this was accompanied by a significant elevation in plasma level of both epinephrine (EPI) (P less than 0.02) and NE (P less than 0.001). Administration of 20 micrograms.kg-1 NX to six dogs resulted in immediate increases in HR (P less than 0.01) and MAP (P less than 0.01), and a further rise in CA levels to greater than pre-fentanyl baseline values. In six other dogs, NBPH (0.3 mg.kg-1) caused increases in HR (P less than 0.001) and MAP (P less than 0.001) only, and the MAP rise was significantly less than that seen in the NX group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311154 TI - Intraoperative awareness due to malfunction of a Siemens 900B ventilator. AB - A case of intraoperative awareness during a thoracotomy is described. The patient's recall coincided with an intraoperative period during which a Siemens 900B ventilator and a Siemens 952 isoflurane vaporiser were used. Subsequent assessment of this equipment with an anaesthetic agent analyzer revealed that, at the ventilator settings which had been used, the delivered anaesthetic vapour concentration varied greatly from the vaporizer settings. This problem eventually was traced to a malfunctioning inlet control valve on the ventilator. This complication may have been prevented if the end-tidal anaesthetic concentration had been monitored intraoperatively. PMID- 2311155 TI - Liability and changing patterns of anaesthetic practice in Canada. PMID- 2311156 TI - Vascular volume monitoring with pulse oximetry during paediatric anaesthesia. PMID- 2311157 TI - Reduction of pain on injection caused by propofol. PMID- 2311158 TI - The length of the blade is more important than its design in difficult tracheal intubation. PMID- 2311159 TI - Intercostal nerve block in obese patients. PMID- 2311160 TI - Atropine-neostigmine mixture. PMID- 2311161 TI - Airway obstruction during anaesthesia in a child with a mediastinal mass. PMID- 2311162 TI - Sporadic PCA pump failure accompanied by activation of a "fail safe" mechanism. PMID- 2311163 TI - Epidural buprenorphine. PMID- 2311165 TI - [Oxygenation through a tracheostomy]. PMID- 2311164 TI - Succinylcholine and Duchenne's muscular dystrophy. PMID- 2311166 TI - Platinum distribution in intraperitoneal tumors after intraperitoneal cisplatin treatment. AB - The spatial distribution of platinum (Pt) in the kidney was studied by an autoradiographic technique, in which cisplatin (CDDP) was replaced by 195mPt labeled CDDP, and by proton-induced X-ray emission (PIXE). Although both studies demonstrated comparable spatial distribution patterns, PIXE had the advantage that Pt concentrations could be determined quantitatively, in contrast to the relative information obtained by the autoradiographic technique. Using PIXE, the distribution of Pt in i.p. tumors was studied after i.p. administration of CDDP. The highest Pt concentrations were always found on the periphery of tumors, indicating that the periphery was exposed to a higher drug concentration than the center. Dose was correlated to the concentration of CDDP at both the center and the periphery (r = 0.99). The Pt concentration in the periphery was usually higher by a factor of 2-3 after i.p. administration than after i.v. treatment, whereas in the center of the tumor no concentration difference could be detected. The penetration depth of CDDP lay between 1 and 2 mm and was calculated from the differences in Pt concentration after i.p. and i.v. treatment. This indicates that the effective advantage of i.p. chemotherapy with CDDP in cases of cancers limited to the peritoneal cavity is accentuated at the periphery of the tumor. PMID- 2311167 TI - Modification of methyliminodiacetato-trans-R,R-1,2-diamminocyclohexane platinum(II) pharmacology using a platinum-specific monoclonal antibody. AB - Platinum complexes are extremely active chemotherapeutic agents. A murine monoclonal antibody designated 1C1 was developed that binds to the third generation platinum complex methyliminodiacetato-trans-R,R-1,2 diamminocyclohexane platinum(II) (MIDP). Competitive enzyme-linked immunosorbent assay (ELISA) shows that antibody 1C1 binds preferentially to the 1,2 diamminocyclohexane (DACH) side-chain of the platinum complex, although non-DACH containing platinum complexes can compete for binding at high concentrations. When tested against MCF-7 breast carcinoma cells, the 1C1-MIDP complex caused 50% growth inhibition at 0.63 micrograms Pt/ml, whereas MIDP alone caused 50% growth inhibition at a concentration of 0.16 micrograms Pt/ml. Pharmacokinetic studies in rats using [3H]-MIDP showed that the drug was cleared triphasically from plasma, with elimination-phase half-lives (t1/2) of 1.2, 10.2, and 243 min for alpha, beta, and gamma phases, respectively. The MIDP-1C1 complex was cleared with longer half-lives of 5, 26, and 291 min, respectively. The overall clearance rate from plasma of the MIDP-1C1 complex was 10-fold lower than that of MIDP alone (0.37 vs 3.01 ml/kg x min). Tissue concentrations of [3H]-MIDP 3 h after administration showed that 1C1 antibody prevented MIDP distribution to most organs and dramatically reduced [3H] concentration in the intestine, liver, kidney, heart, and skeletal muscles. Studies are under way to determine the relative therapeutic activity of the 1C1 antibody-MIDP complex and assess whether the 1C1 antibody may be useful for antibody-directed delivery of platinum complexes to tumors. PMID- 2311168 TI - Metallothionein-like proteins and cell resistance to cis dichlorodiammineplatinum(II) in L1210 cells. AB - Our studies on the mechanism of resistance of the murine leukemia L1210-PDD line to cis-dichlorodiammineplatinum(II) (cis-DDP) have not shown why it is 10-fold more resistant to the drug than the L1210 line. For this reason we investigated metallothionein-like proteins ('MTs') in these cells. Soluble protein extracts from cultures treated for 24 h with cis-DDP, zinc sulphate or saline were anaerobically eluted from columns of chemically reduced Sephadex G-75, and the profiles of zinc, copper and platinum were determined along with those for incorporated radioactive cyst(e)ine and tyrosine. Both saline-treated cell lines contained similar levels of 'MTs', which were induced by exposure to a minimally toxic level of zinc (100 microM). Zinc induction of 'MTs' was nearly 4-fold greater in L1210 than in L1210-PDD cells. The levels of mRNA for metallothionein I (MTI) and II (MTII) in uninduced cells were measured by dot-blotting with a cDNA probe. The L1210-PDD cells contained 80% of the MTI and 41% of the MTII compared with L1210 cells, confirming the similar levels in uninduced cells. L1210-PDD cells were 2-fold more sensitive than L1210 cells to cadmium and equally sensitive to zinc. Thus, the resistance of L1210-PDD cells to cis-DDP was not associated with cross-resistance to group IIb metals, whereas their sensitivity to cadmium did reflect the relative inability of the cells to synthesize 'MTs'. The L1210 cells produced 'MTs' when treated with 0.5 and 5.0 microM cis-DDP, but the L1210-PDD cells did not when treated with 5.0-40 microM cis-DDP. Small amounts of platinum (less than 21% of the total eluted) were bound to 'MTs' in both cell lines, but platinum provided a minor portion of the 'MT' bound metals, with zinc and copper contributing the bulk. The basis for the resistance of L1210-PDD cell to cis-DDP is neither an increased level of 'MTs' in the resistant cells nor an enhanced ability to increase the synthesis of 'MTs' after drug exposure. PMID- 2311169 TI - The effect of ara-C-induced inhibition of DNA synthesis on its cellular pharmacology. AB - The cytotoxicity of ara-C is believed to result from incorporation of ara-CTP into DNA and inhibition of DNA synthesis. Since complete inhibition of DNA synthesis would prevent further incorporation of ara-CTP, ara-C may have a self limiting effect on its own cytotoxicity, particularly at the high concentrations typical of high-dose ara-C clinical protocols. In this study, the incorporation of [3H]-dThd and [3H]-ara-C into DNA were compared. Within 1 h of exposure of L5178Y cells to ara-C, the rate of [3H]-dThd incorporation into the acid insoluble fraction was reduced by 98%. Despite this nearly complete block in [3H] dThd incorporation, DNA synthesis was not completely inhibited since [3H]-ara-C continued to be incorporated for up to 6 h, although a plateau in ara-CDNA synthesis was observed between 2 and 3 h exposure when ara-CTP levels were maximal. The effect of ara-C on [3H]-dThd incorporation into DNA was due in part to an indirect effect of ara-C on the metabolism of intracellular [3H]-dThd to [3H]-dTTP. Within 30 min exposure to 10 microM ara-C, the rate of cellular [3H] dTTP synthesis was slowed to only 15% of the control rate. This was not due to inhibition of [3H]-dThd transport, since the intracellular and extracellular concentrations of the nucleoside were equal. The effect of ara-C on [3H]-dTTP synthesis resulted from significant changes in deoxynucleoside 5'-triphosphate (dNTP) pools. dTTP, dATP, and dGTP levels were increased, whereas the dCTP concentration was decreased. When dThd kinase from L5178Y cells was assayed with increased dTTP levels induced by ara-C vs the dTTP level in control cells, its activity was reduced by 72%. Thus, the [3H]-dThd incorporation experiment overestimated the extent of inhibition of DNA synthesis by ara-C due to increased feedback inhibition of dThd kinase and increased competition for DNA polymerase between the elevated unlabeled dTTP pool and the decreased levels of [3H]-dTTP. In vitro assay of DNA polymerase in the presence of the ara-CTP concentration achieved after 0.5 or 3 h exposure to 10 microM ara-C (60 microM and 200 microM, respectively), plus the mixture of dNTPs found intracellularly at these times, resulted in 57% and 80% inhibition of the polymerase, respectively. This inhibition may account for the plateau in the accumulation of ara-CDNA that was observed at 3 h and suggests that ara-C incorporation may be self-limiting at high cellular concentrations of ara-CTP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2311170 TI - Schedule dependence, activity against natural metastases, and cross-resistance of pyrazine diazohydroxide (sodium salt, NSC 361456) in preclinical models in vivo. AB - Pyrazine diazohydroxide (sodium salt, NSC 361456; PZDH) is a new antitumor drug with relatively broad activity in initial evaluations against murine leukemias, solid tumors, and two human tumor xenografts in vivo. The present studies were designed to address questions about PZDH activity on different treatment schedules, its activity against metastases, and the extent of its cross resistance with established drugs. Human LOX amelanotic melanoma xenografts in athymic mice were used to explore schedule dependence and activity against natural metastases, and a series of drug-resistant murine leukemias provided an in vivo cross-resistance profile. Single-dose treatment and prolonged treatment provided equivalent therapeutic responses to PZDH by both the i.p. and i.v. routes in the i.p. LOX model. A s.c. LOX model resulting in spontaneous pulmonary metastases was adapted for bioassay and quantitation of the numbers of LOX cells killed by PZDH among both primary and metastatic cell populations. It was demonstrated that PZDH afforded about 2-log10 orders of magnitude greater cell kill among pulmonary metastases than against primary s.c. LOX tumors in the same mouse. Murine leukemias resistant to doxorubicin (ADR), vincristine (VCR), cisplatin (DDPt), methotrexate (MTX), N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), and cyclophosphamide (CPA) were not cross-resistant to PZDH. However, both P388 and L1210 leukemia sublines resistant to melphalan (L-PAM) were cross resistant to PZDH, suggesting that patients previously treated with L-PAM might have less likelihood of response to PZDH than those who had had no opportunity to develop L-PAM resistance. Although these observations should not be applied to clinical studies without due caution, they support clinical evaluation of PZDH as well as continued investigation of its molecular pharmacology. PMID- 2311171 TI - DNA damage and cytotoxicity of mitoxantrone and doxorubicin in doxorubicin sensitive and -resistant human colon carcinoma cells. AB - The effects of mitoxantrone (Mx) and doxorubicin (Dx) on cytotoxicity and DNA damage as assayed by alkaline elution were studied in two human colon adenocarcinoma cell lines sensitive (LoVo) and resistant (LoVo/Dx) to doxorubicin. Mx was more cytotoxic than Dx to LoVo cells and was partially cross resistant in LoVo/Dx. In LoVo cells, Mx produced about 5 times more DNA single strand breaks (DNA-SSB) than Dx, but both drugs caused an equal number of DNA double-strand breaks (DNA-DSB). In LoVo/Dx cells, the number of DNA-DSB was very low for both Dx and Mx, but DNA-SSB were about 20 times higher for Mx. In LoVo cells, the number of DNA-DSB and protein-associated SSB were similar at equitoxic concentrations. For LoVo/Dx, the partial cross-resistance of Mx might be explained by the much higher number of DNA-SSB produced by this drug. PMID- 2311172 TI - Comparative pharmacokinetics of escalating doses of doxorubicin in patients with metastatic breast cancer. AB - Recombinant human granulocyte colony-stimulating factor (G-CSF) has been shown to reduce neutropenia following cytotoxic therapy, thereby enabling dose escalation to improve the response rate. It is important to know whether drug kinetics change as doses are increased. Doxorubicin was selected because of its broad spectrum of activity and its known efficacy in metastatic breast cancer. Doses of 75, 100, 125 and 150 mg/m2 were given to 11 patients with metastatic breast cancer by infusion over 30 min. Serum concentrations of parent drug and metabolites were determined during the first 48 h following the infusion by high performance liquid chromatography (HPLC). The serum concentration vs time curve decayed as a triple exponential function in four patients and as a double exponential function in seven. A four-compartment model, one central and three peripheral, would predict concentrations to within 1 SE of the observed values. Doxorubicinol was the principal metabolite, and doxorubicinone and 7 deoxydoxorubicinone were clearly identified. There was a linear increase in the AUC infinity with dose. In addition, a small and transient increase in circulating levels of doxorubicinol and other important metabolites was observed 6 h following the administration of doxorubicin, which suggests the existence of an enterohepatic, or other, re-circulation mechanism. We conclude that in the dose range selected the kinetics of doxorubicin are linear and that the increase in toxicities seen with the higher doses of doxorubicin, following the second and third fortnightly administration, may be due to intracellular drug accumulation in tissues. PMID- 2311173 TI - Pharmacokinetics of reduced folates after short-term infusion of d, 1-folinic acid. AB - After the use of d,1-folinic acid (d,1-CHO-THF), pharmacokinetic measurements should take into account 1-CHO-THF and its metabolite 1-methyltetrahydrofolic acid (1-CH3-THF) as well as d-CHO-THF. For this purpose, we developed a simple and rapid assay by combining reversed-phase HPLC to determine total levels of d,1 CHO-THF and CH3-THF and chiral HPLC to separate the biologically active 1-CHO-THF from the inactive d-CHO-THF. We investigated the pharmacokinetics after short term infusion of 300 mg d,1-CHO-THF in ten healthy volunteers. With a mean of 56.5 min, 1-CHO-THF exhibits a rapid body clearance of 222 ml/min, about 60% of which is caused by metabolism to CH3-THF and 40%, by renal excretion. CH3-THF has a terminal half-life of 208 min and a total body clearance of 88.9 ml/min, which is essentially the same as the renal clearance. Due to the lower clearance of CH3 THF, its AUC (2,132 microM x min) exceeds that of 1-CHO-THF (1445 microM x min) by approximately 50%. In contrast to that of the reduced 1-folates, the total body and renal clearance of d-CHO-THF is very low, with values of 13.2 and 12.9 ml/min, respectively. This results in a very high AUC of 24, 269 microM x min, which is higher by factors of 17 and 11 than those of 1-CHO-THF and CH3-THF, respectively. The implications of the distinct kinetics of the reduced 1-folates and d-CHO-THF for the efficacy of folinic acid/5-fluorouracil therapy and adequate protocols for the treatment of advanced colorectal cancer are discussed. PMID- 2311174 TI - Pharmacokinetics of 4-demethoxydaunorubicin in cancer patients. AB - The clinical pharmacokinetics of 4-demethoxy-daunorubicin was investigated in 28 cancer patients who received the drug orally. The majority of the patients were elderly (median age, 72 years). Nine of them also received an i.v. dose, and the bioavailability of the oral dose ranged between 9% and 39%. 4 Demethoxydaunorubicin peak levels were achieved 2-4 h after the oral dose in most patients. The drug was rapidly and extensively metabolized to 4-demethoxy-13 hydroxydaunorubicin, which is probably as active as the parent drug. The metabolite levels were much higher and longer lasting than the parent drug, suggesting that it may play an important role in the drug's pharmacological effects. PMID- 2311175 TI - Extremely prolonged continuous intraperitoneal infusion of cytosine arabinoside. AB - Intraperitoneal administration of ara-C produces a peritoneal/plasma concentration ratio of 330-1,000: In principle, optimal tumor-cell kill should be obtained when high ara-C concentrations ar maintained in the environment of the tumor for very long periods of time. A phase 1 study was undertaken to determine the maximum tolerated dose of ara-C that could be given as a continuous i.p. infusion for 3 weeks. A total of 14 patients with refractory malignancies were given 28 courses in the outpatient setting. Ara-C infusions were given using a portable programmable pump (Pancreatec Provider Model 2000). No significant side effects were observed in patients receiving 30 mg/m2 per day (five courses) or 40 mg/m2 per day x 21 days (seven courses). However, at a dose of 60 mg/m2 per day, although 10/16 courses were tolerated for at least 1 week, only 3/16 attempted courses could be continued for the full 3 weeks. The dose-limiting toxicity was chemical peritonitis, which occurred during 7/16 courses at this dose level and required termination of therapy in 4 courses. Myelosuppression was also observed at this dose. There was a large variation in the ara-C and ara-U peritoneal concentrations both within and between patients. The mean peritoneal ara-C concentration increased nonlinearly with ara-C dose whereas the mean ara-U concentration decreased. This study establishes the feasibility and safety of giving a cell-cycle-specific drug intraperitoneally over an extremely prolonged period. For subsequent studies a dose of 40 mg/m2 per day for 21 days is recommended. PMID- 2311176 TI - Phase II study of teniposide in advanced breast cancer. AB - In a phase II study, 19 patients with previously treated, advanced breast cancer received 50 mg/m2 teniposide (VM-26) i.v. on days 1-5 every 3 weeks. One partial response (PR) (5%) was observed. Toxicity consisting of leukopenia and thrombocytopenia was frequent and severe. VM-26 has minimal therapeutic activity when given at this dose and on this schedule to patients with heavily pretreated metastatic breast cancer. PMID- 2311177 TI - Pharmacokinetics of N-nitrodimethylamine and N-nitromethylamine in the rat. AB - Oxidative metabolism of radioactively labeled N-nitrodimethylamine in rats was compared with that of N-nitromethylamine. Within 7 h, 20% of N-nitrodimethylamine was metabolized to CO2 but only 4% of N-nitromethylamine. The poor oxidative metabolism of N-nitromethylamine is also reflected in the blood levels determined after i.v. administration to catheterized rats. N-Nitrodimethylamine was cleared rapidly from rat blood, while N-nitromethylamine was rapidly distributed into body water but had a long elimination half-life. An amount equal to 5.2% of the dose of the monomethyl compound was excreted intact in urine, but only 0.004% of the dimethyl compound. The pharmacokinetic data obtained were compared with the published data on the pharmacokinetics of the structural analog N nitrosodimethylamine. PMID- 2311178 TI - Prolonged survival of female AKR mice fed diets supplemented with methionine and choline. AB - Female mice of the AKR/J (AK) strain were fed a control diet (Purina Rodent Laboratory Chow) or a lipotrope-supplemented diet (Purina Rodent Chow plus 2% D,L methionine and 1% choline chloride) beginning at 1 day after weaning. Food consumption and weight gain were found to be the same in both groups of animals. Mice of this inbred strain spontaneously develop thymic lymphoma, with close to 100% mortality expected by 12-13 months of age. Two separate experiments were carried out with 50 mice per group in one, and 40 mice per group in the other. The slopes of the survival curves for the animals in the control group and supplemented group of mice diverged after the animals reached 6.5 months of age. In both experiments, 20% of the mice receiving supplemented diet were still alive at 1 year, while 3% in one experiment and 8% in the other experiment survived in the control groups. Each experiment was terminated when the animals reached 13 months of age. At that time the survival rate of the controls was 2 and 4%, and survival in the groups of mice receiving supplemented diet was 14 and 18%. Necropsy revealed that the animals in both groups had advanced malignant lymphoma. Our results demonstrate that intake of a chow diet that is supplemented with moderate quantities of methionine and choline results in enhanced survival of spontaneously leukemic AK mice, in comparison with animals of this strain fed the same diet without supplements of choline and methionine. PMID- 2311179 TI - The effects of teleocidin and aplysiatoxin tumor promoters on epithelial tight junctions and transepithelial permeability: comparison to phorbol esters. AB - Control of transepithelial permeability by regulation of tight junctions is exerted by the non-phorbol ester tumor promoters, teleocidin and aplysiatoxin. Similar to the phorbol esters, tetradecanoylphorbol-13-acetate (TPA) and phorbol dibutyrate (PDBU), both teleocidin and aplysiatoxin cause a reversible decrease of transepithelial voltage and transepithelial resistance across LLC-PK1 renal epithelial cell sheets at concentrations as low as 10(-8) M. These compounds are effective from either side of these polar epithelial cells, i.e. apical or basolateral. The decreases in transepithelial gradients and resistance are paralleled by a rise in the transepithelial (paracellular) flux of D-mannitol between the cells (through the tight junctions). These four tumor promoters, TPA, PDBU, teleocidin and aplysiatoxin, are all known protein kinase C activators, and support the case for protein-kinase-C-mediated control of tight junctional permeability. PMID- 2311180 TI - Effects produced by the non-genotoxic hepatocarcinogen methylclofenapate in dwarf mice: peroxisome induction uncoupled from DNA synthesis and nuclearity changes. AB - Both Snell dwarf mice (dw/dw) and their phenotypically normal heterozygotes (dw/+) were dosed with methylclofenapate (MCP) at daily intervals by gavage (25 mg/kg). Animals were killed at 12, 24, 36 and 72 h after the initial dose and the parameters of ploidy, nuclearity and DNA synthesis were measured in hepatocytes isolated by collagenase perfusion. The occurrence of peroxisome proliferation was assessed by electron microscopy after daily administration of 25 mg/kg MCP by gavage for 28 days. The hepatocytes from both phenotypes exhibited similar degrees of peroxisome proliferation but hyperplasia occurred only in the heterozygous animals. The incidence of binulceated hepatocytes in heterozygotes was approximately 50%, and at the end of acute hyperplasia this had reduced to approximately 20%; by contrast the livers of dwarf animals contained approximately 20% binucleated cells and this remained unchanged throughout the period of dosing. The hyperplasia in the wild-type mice, as measured by the occurrence of S-phase, occurred predominantly in binucleated hepatocytes. These observations are further confirmation that acute hyperplasia induced by MCP and similar liver growth inducers occurs predominantly in a sensitive sub-population of binucleated hepatocytes. The results also indicate that peroxisome proliferation and hyperplasia can occur as independent phenomena. PMID- 2311181 TI - Effects of various prostaglandin synthesis inhibitors on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine. AB - The effects of prostaglandin synthesis inhibitors on development of N nitrosobis(2-oxopropyl)amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given five weekly s.c. injections of BOP (10 mg/kg body weight) during the first 5 weeks and then given 20 p.p.m. indomethacin in the drinking water, 0.25% phenylbutazone in the diet, 1% aspirin in the diet, or no treatment (control group). The resultant incidence of pancreatic carcinoma at week 32 was significantly lower (P less than 0.05) in animals receiving phenylbutazone (36.8%) than in the controls (71.4%) and the numbers of carcinomas per hamster were significantly reduced by indomethacin (0.63) and phenylbutazone (0.58) treatment compared with the control group value (1.29). Aspirin also showed a tendency to decrease pancreatic tumor incidence, but this was not significant. Thus, prostaglandin synthesis inhibitors reduce the development of pancreatic cancer when administered during the post-initiation phase in this animal model. PMID- 2311182 TI - Mouse skin tumorigenicity studies of indoor coal and wood combustion emissions from homes of residents in Xuan Wei, China with high lung cancer mortality. AB - The rural Xuan Wei County, Yunnan Province, China, has an unusually high lung cancer mortality rate that cannot be attributed to tobacco smoke or occupational exposure. The lung cancer rate is associated with 'smoky' coal, in contrast to wood or 'smokeless' coal burned in unventilated homes. This study was conducted to characterize and compare mouse skin tumorigenicity of the coal and the wood combustion emissions and to link the animal data to human lung cancer. Indoor air particles (less than 10 microns) were collected from a central commune where the lung cancer mortality rate is high and smoky coal is the major fuel used and also from a south-western commune where lung cancer mortality rate is low and where wood or smokeless coal are the major fuels used. The organic extracts of these indoor air particles from smoky coal, smokeless coal and wood combustion were analysed for polycyclic aromatic hydrocarbons and assayed for skin tumor initiation activity and complete carcinogenicity in SENCAR mice. The results showed that the organic extract of the emission particles from smoky coal combustion is the most active in tumor initiation among the three combustion emission samples followed by smokeless coal and then wood. The organic extract of the particles from smoky coal combustion was shown to be a potent complete carcinogen, whereas the wood extract was relatively inactive as a complete carcinogen. The extract of particles from the smokeless coal combustion was not tested for complete carcinogenicity because of inadequate supply. Eighty-eight percent of the mice treated with the smoky coal extract showed carcinomas, averaging 1.1 carcinomas per tumor-bearing mouse at the end of the 77 week study. These findings were in agreement with the epidemiological data, which showed that the Xuan Wei residents using smoky coal as a major fuel in homes had a high lung cancer mortality rate. This study demonstrates that the results of the tumorigenicity assays in mice were in agreement with human lung cancer data. PMID- 2311183 TI - Gastric nitrite processing in the surgically altered maximal and minimal bile reflux ferret model. AB - Ingested nitrate and nitrite have been shown to contribute to endogenous, N nitroso compound formation in man and experimental animals. N-nitroso compounds have long been suspected of contributing to higher levels of gastric cancer in various populations. Reconstructive gastric surgery to treat ulcers is accompanied by a change in bile reflux, gastritis and an increased incidence of gastric cancer in humans. To evaluate possible connections between gastric nitrite processing, reconstructive surgery and gastric cancer, the surgically altered domestic ferret, Mustela putorius furo, was used as an experimental model. The aim of the study was to determine if surgery would alter the stomach in a way which would increase gastric nitrite concentration, and thereby enhance the likelihood of gastric N-nitroso compound formation. Three groups of ferrets, one control group (n = 6) and two groups of surgically altered ferrets, one to simulate maximal bile reflux (MABR, n = 6), and the other to model minimal bile reflux (MIBR, n = 7), were studied. Each group's response to an exogenously administered dose of sodium nitrite did not differ significantly with respect to rate of gastric nitrite absorption, with half-lives in the 13-min range. Permeability of gastric mucosa to nitrite did not differ between controls and MIBR ferrets. Mean doubling time of gastric nitrate appeared slowed in surgically altered ferrets. Mean rate of gastric emptying was the same in the three groups, but appeared delayed initially in MIBR ferrets. Thiocyanate concentrations, pH and HCl secretion, all parameters which have been shown to affect gastric nitrite processing, did not differ significantly between groups. Gastric mucosal endoscopic biopsies obtained at 6-month intervals showed no clear difference in degree of mucosal inflammation and/or dysplasia in the three groups. These findings indicate that gastric mucosal neoplasia has not occurred in this model and that changes in parameters favoring gastric N-nitrosation, even if relevant to the disease process, are not apparent at this time. PMID- 2311184 TI - DNA methyl-adduct dosimetry and O6-alkylguanine-DNA alkyl transferase activity determinations in rat mammary carcinogenesis by procarbazine and N methylnitrosourea. AB - The metabolism of the carcinogenic antitumor drug procarbazine (PCZ) is complex with the ultimate production, among other metabolites, of a methyldiazonium ion which is also the ultimate carcinogenic species of the DNA-methylating N-nitroso compounds including N-methylnitrosourea (MNU). This suggests a similar mechanism of carcinogenic action. Following a single oral dose of [14C]PCZ (50 mg/rat) to 50 day old female Sprague-Dawley rats under the reported conditions of mammary gland carcinogenicity, the DNA adducts 7-methylguanine (7-meG) and O6 methylguanine (O6-meG) were determined in target (mammary gland) and non-target organs. The degree of DNA methylation was similar in all the organs considered. In the mammary gland, lung, spleen, small intestine and stomach the O6-meG/7-meG ratio was close to 0.11. At a lower dose of PCZ (26 mg/rat), the levels of 7-meG in the tissues were 40-60% of those produced by the higher dose. Eighty percent of the rats given the higher dose versus 37% of those given the lower dose developed mammary tumors after 20 weeks. With the higher dose of MNU (50 mg/kg body wt) DNA methylation was more or less uniform in all the organs including the mammary gland, with slightly greater yields in the liver. At a lower MNU dose (25 mg/kg) the levels of 7-meG were 40-48% of those produced by the higher dose. Fifty seven percent of the rats given the higher dose versus 21% of the animals given the lower dose developed mammary gland tumors after 20 weeks. On a mol/kg body wt basis, PCZ was approximately 5-times less active than MNU in the production of 7-meG in mammary gland but only approximately 2-times less active than MNU in the production of mammary gland tumors. The O6-alkylguanine-DNA alkyltransferase (AGT) levels in the liver, kidney, spleen and lung of PCZ or MNU treated rats were approximately 9-28% (expressed relative to protein content) and 10-33% (expressed relative to homogenate DNA content) of those in the corresponding organs of the saline-treated controls. However, the AGT levels of the mammary gland and brain were in the range of 45-61% (expressed relative to protein content) and 39-54% (expressed relative to homogenate DNA content) of those of the saline-treated controls. Also the mammary gland of the 50 day old female rats has the lowest AGT activity (expressed relative to DNA content).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2311185 TI - Formation of the DNA adduct S-[2-(N7-guanyl)ethyl]glutathione from ethylene dibromide: effects of modulation of glutathione and glutathione S-transferase levels and lack of a role for sulfation. AB - Hepatic S-[2-(N7-guanyl)ethyl]glutathione DNA adducts were determined in several strains of rats and mice after i.p. injection of a dose of 37 mg ethylene dibromide/kg body wt. More adducts were formed in rats than in mice, while no difference was noted among strains within each species. Removal of adducts in liver DNA was relatively slow in all animals tested. On the contrary, in vitro incubation of calf thymus DNA with ethylene dibromide and either rat cytosol or mouse cytosol gave rise to similar amounts of adduct, yet mouse cytosol showed much higher glutathione (GSH) S-transferase activity toward 1-chloro-2,4 dinitrobenzene. Human cytosol also activated ethylene dibromide, with the extent of conjugation being approximately half that of rat cytosol. Pretreatment of rats with phenobarbital or beta-naphthoflavone induced GSH S-transferases but did not increase the in vivo formation of DNA adducts, suggesting that concomitant induction of cytochrome P450 might abolish the effect of induction of GSH S transferase by increasing the oxidation of ethylene dibromide. Butylated hydroxytoluene induced GSH S-transferase and also markedly increased DNA adduct levels. Disulfiram, a known cytochrome P450 inhibitor, significantly increased the formation of DNA adducts whereas it did not affect GSH S-transferase activity. Depletion of GSH by pretreatment of rats with diethylmaleate or buthionine sulfoximine resulted in decreased in vivo DNA adduct levels and the degree of reduction was well correlated with the extent of GSH depletion. In vitro incubation of tritiated S-(2-hydroxyethyl)GSH with calf thymus DNA in the presence of 3'-phosphoadenosine-5'-phosphosulfate and rat liver cytosol did not result in significant binding to DNA, suggesting that sulfation of the alcohol does not readily occur to add a leaving group and regenerate an episulfonium ion. These results suggest that induction of the Phase II enzyme GSH S-transferase can be detrimental in the case of ethylene dibromide and that decreases in GSH levels reduce DNA alkylation in rats. PMID- 2311186 TI - Early proliferative responses of forestomach and glandular stomach of rats treated with five different phenolic antioxidants. AB - The effects of 8 weeks of oral administration of five different phenolic antioxidants, e.g. catechol (CC), resorcinol, hydroquinone (HQ), 2-tert-butyl-4 methylphenol (TBMP) and propylparabene (PP), on forestomach and glandular stomach epithelium of male F344 rats were evaluated using a combined immunohistochemical and histopathological approach. Treatment with CC and TBMP induced a significant elevation of DNA synthesis in the forestomach epithelium, associated with hyperplasia. CC administration also brought about an increase of DNA synthesis in the pyloric gland mucosa, cell proliferation in this case being reflected by an increment in the crypt height. In addition to causing an increase in the pepsinogen-isozyme-1-altered pyloric glands (PAPG), which are considered to be putative preneoplastic precursor lesions in the rat glandular stomach, CC treatment was associated with submucosal growth of pyloric mucosal cells tending to decreased pepsinogen isoenzyme 1 binding. However, DNA synthesis values in these latter areas were lower than in pyloric glands of the control group. In contrast, other phenolic compounds, resorcinol, HQ and PP, did not induce any changes in the stomach mucosa. The present results demonstrated strong proliferative responses in the stomach epithelium for CC and TBMP, indicative of promoting potential in both cases, and suggest that CC and TBMP may exert detrimental effects leading to promotion of stomach carcinogenesis or cancer development via an early proliferative response. PMID- 2311187 TI - Studies in gastric carcinogenesis. IV. O6-methylguanine and its repair in normal and atrophic biopsy specimens of human gastric mucosa. Correlation of O6 alkylguanine-DNA alkyltransferase activities in gastric mucosa and circulating lymphocytes. AB - DNA extracted from biopsies of normal or atrophic gastric mucosa obtained from 20 individuals was analysed for the presence of the precarcinogenic alkylation lesion O6-methylguanine by a recently developed, highly sensitive assay based on repair by the Escherichia coli O6-alkylguanine-DNA alkyltransferase (AGT) enzyme in competition with a radiolabelled oligonucleotide containing O6-methylguanine (O6-meG). With a limit of detection of 0.5 fmol O6-meG in 10 micrograms DNA, only one DNA sample (derived from a region of the stomach with advanced chronic atrophic gastritis) was found marginally positive, containing 0.52 fmol/10 micrograms DNA (8.3 X 10(-8) mol O6-meG/mol guanine). Measurements of AGT in 49 biopsies of normal, atrophic, hyperplastic or dysplastic mucosa obtained from the gastric antrum or corpus of 18 individuals did not reveal any significant effects of mucosal histology on AGT. The average AGT value found was 6.9 +/- 3.5 (SD) fmol/micrograms DNA, which is lower than the values reported for a number of other human tissues (liver, small intestine and lung). Measurement of AGT levels in gastric mucosa and circulating lymphocytes of the same individuals revealed a positive correlation (P less than 0.005), suggesting that lymphocytes may serve as a useful surrogate marker for AGT activity in gastric mucosa in studies of the epidemiology of this important repair enzyme. PMID- 2311188 TI - Long-term effects of hypolipidemic peroxisome proliferator administration on hepatic hydrogen peroxide metabolism in rats. AB - The effects of prolonged dietary administration of peroxisome proliferators, such as clofibrate, bezafibrate and di(2-ethylhexyl)phthalate (DEHP), on hepatic hydrogen peroxide (H2O2) level and on hepatic activities of the enzymes relating to H2O2 metabolism were examined. Male rats were treated for 79 weeks with the above three peroxisome proliferators. The activities of the peroxisomal beta oxidation and catalase were increased 8- to 20-fold and 2- to 3-fold, respectively, after 2 or 4 weeks of treatment with these peroxisome proliferators. However at 79 weeks the peroxisomal beta-oxidation activity was 3 8 times that of control. The level of catalase activity was kept at approximately 2-fold even after prolonged treatment of peroxisome proliferators. Although the activities of glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) were decreased 50-60% at 4-12 weeks by the treatment with peroxisome proliferators, from 20 to 79 weeks those activities approached control levels in the case of clofibrate and bezafibrate but not DEHP-fed rats; GSH-Px and GST activities were kept at approximately 40% those of control. However hepatic capacities of H2O2-degrading enzymes, catalase and GSH-Px, apparently exceeded the H2O2-generating levels obtained on the basis of peroxisomal beta-oxidation activities in the livers of control and treated rats throughout the experimental period. The hepatic H2O2 levels increased only slightly but this increase did not correspond to changes in peroxisomal beta-oxidation. Our results suggest that a large part of H2O2 produced by peroxisomal beta-oxidation could be rapidly scavenged by catalase and GSH-Px in the liver of rats treated with peroxisome proliferators. PMID- 2311189 TI - Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. AB - Glutathione S-transferases play a central role in drug detoxification and have been implicated in the sensitivity of tumour cells to anticancer drugs. In this study, glutathione S-transferase (GST) isozyme expression in normal and tumour tissue from human lung, colon, stomach, breast, kidney and liver tissue has been quantified using sensitive and subunit specific radioimmunoassays (RIA), together with Western blot analysis and measurement of substrate metabolism. Glutathione S transferase pi was the predominant GST in the majority of the tumours examined. The concentration of this enzyme was increased significantly in tumour tissue relative to normal lung, colon, and stomach tissue. A strong correlation was observed (r = 0.77, P less than 0.01) between GST activity and GST pi levels in those tumour samples. The concentrations of the alpha class GST, the predominant isoenzymes in normal stomach, kidney and liver, decreased dramatically in tumour tissue from these organs. Western blot analysis revealed the presence of novel polypeptides that cross-reacted with antisera raised against alpha and mu class GST. Our data demonstrates that although GST pi is the predominant GST isoenzyme in many tumours, significant levels of the other GST subunits are also present and collectively can represent a significant proportion of the GST content. Therefore the properties of all the GST isoenzymes need consideration when assessing the role of these proteins in drug resistance. Selenium-dependent glutathione peroxidase, an enzyme activity also implicated in the mode of action of certain antitumour agents, was also studied and shown to be the predominant glutathione-dependent peroxidase in all tumours except the hepatoma. PMID- 2311190 TI - The O-methylation of 4-hydroxyestradiol is inhibited by 2-hydroxyestradiol: implications for estrogen-induced carcinogenesis. AB - O-Methylation of catecholestrogens catalyzed by catechol-O-methyltransferase provides a major route for the rapid metabolic clearance of these steroids. However, the metabolic clearance rate of 4-hydroxyestradiol (4-OH-E2) is considerably lower than that of 2-hydroxyestradiol, although 2- and 4 hydroxycatecholestrogens (2- and 4-OH-CE) have similar apparent affinities for the enzyme. To determine the reason for this apparent paradox we have examined whether the efficiency of O-methylation of 4-OH-E2 could be affected by other catecholestrogens or their O-methyl ethers. The ratio of 4-methoxyestradiol:4 hydroxyestradiol 3-methyl ether was 2.6 at pH 8.5, the pH optimum for the reaction. The O-methylation of 4-OH-E2 (apparent Km 10 microM) was inhibited by 2 hydroxyestradiol (2-OH-E2) but not by 2- or 4-methyoxyestrogens. The values for Km, Vmax as well as the slope for the methylation of 4-OH-E2 were altered by 2-OH E2 indicating a mixed inhibition. The inhibition constant for the intercept 1/V'max versus 2-OH-E2 concentrations and the inhibition constant for the slope versus 2-OH-E2 concentrations were 35 and 5.7 microM, respectively. The inhibition of O-methylation of 4-OH-E2 by 2-OH-E2 increased with the pH. In target tissues of the carcinogenic action of estrogens such as the rat pituitary, hamster kidney, or mouse uterus in which 2- and 4-OH-CE are both generated in almost equal amounts, the inactivation of 4-OH-CE by O-methylation may be impeded. Consequently, 4-OH-E2 would remain available as substrate for redox cycling, generation of active radicals and DNA damage. PMID- 2311191 TI - Gene amplification affecting O(6)-alkylguanine-DNA alkyltransferase activity is not detected in nitrosourea resistant or sensitive human cell lines. AB - An attempt was made to characterize the genetic regulation of the human DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) in the absence of the cloned gene. Four human cell lines, differing in AGT activity from very proficient to essentially absent, were assayed for gene amplification as a possible mediator of the methylation repair phenotype (Mer+, AGT activity and MER , no AGT activity) using in-gel DNA renaturation and G-banded karyotype analysis. The former technique allows subsequent analysis of amplification units and cloning of observed amplified DNA fragments, a hopeful approach to the isolation of the human AGT gene. Within the sensitivities of the techniques, no correlation between AGT activity and gene amplification was observed in the four cell lines tested. PMID- 2311192 TI - Glutathione conjugation protects some, but not all, cell lines against DNA binding of benzo[alpha]pyrene metabolites. AB - Three major types of cell lines were distinguished according to their capacity for glutathione (GSH) conjugation of extracellularly generated benzo[alpha]pyrene (BaP) metabolites, and the level of DNA binding of such metabolites. (i) Cells, e.g. HepG2, which conjugate BaP metabolites only very poorly with GSH and are highly susceptible to DNA binding. The number of DNA adducts in these cells (approximately 10 pmol/mg DNA) is taken to be the maximum DNA binding in 'unprotected' cells. (ii) Cells, e.g. V79 and NCI-H322, which efficiently conjugate BaP metabolites with GSH but, like HepG2 cells, are 'unprotected' as indicted by maximum DNA binding. (iii) Cells, e.g. 2sFou and H4IIEC3/G-, which are positive for GSH conjugation and exhibit only very little DNA binding. When GSH conjugation in these apparently 'protected' cells is suppressed by depletion of GSH, the level of DNA binding increases to that found in 'unprotected' lines. GSH depletion does not substantially affect DNA binding in 'unprotected' cells. The results show that, although GSH conjugation is capable of suppressing DNA binding of reactive BaP metabolites in some cell types, it fails to protect against DNA binding in others. It is possible that the reactive species are compartmentalized and certain cell types are protected, because they are able to specifically trap those BaP metabolites which bind to DNA. PMID- 2311193 TI - Differential rates of metabolic activation and detoxication of the food mutagen 2 amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by different cytochrome P450 enzymes. AB - Rat liver microsomes metabolized the food mutagen 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP) to the genotoxic metabolite 2-hydroxamino-1 methyl-6-phenylimidazo[4,5-b]pyridine (2-hydroxamino-PhIP) and to the detoxified product 2-amino-4'-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine (4'-hydroxy PhIP). A 25-fold higher rate of metabolism was measured in microsomes from polychlorinated-biphenyl-treated rats (94 nmol/mg proteins/30 min) in comparison with those from untreated rats. Other effective inducers of PhIP metabolism were beta-naphthoflavone and isosafrole (ISF), whereas phenobarbital was ineffective. About twice as much 2-hydroxamino-PhIP as 4'-hydroxy-PhIP was formed in microsomes irrespective of the inducer the rats had been treated with. The metabolism was dependent on NADPH and was abolished by the cytochrome P450 inhibitor alpha-naphthoflavone. In a reconstituted enzyme system purified rat cytochrome P450 IA2 (P450ISF-G) had the highest N-hydroxylation rate (30 nmol/nmol P450/30 min) closely followed by the rat cytochrome P450 IA1 (P450BNF B). Less activity was seen with rat P450 IIC11 (P450UT-A) and rabbit P450 IA2 (P450 LM4). Rat P450 IIE1 (P450j), P450 IIB1 (P450PB-B) and rabbit P450 IIB4 (P450 LM-2) and P450 IIE1 (P450 LM3a) were essentially inactive. Rat P450 IA1 (P450BNF-B) produced five times more 4'-hydroxy-PhIP (32 +/- 2 nmol/nmol P450/30 min) than did P450 IA2 (P450ISF-G). Hence, the measured ratio of activation to detoxication for rat P450 IA2 (P450ISF-G) enzyme was 7-fold higher than that of the other active P450 enzymes. PMID- 2311194 TI - The site of substitution of the methyl group in the bioalkylation of benzo[a]pyrene. AB - The major product of the S-adenosyl-L-methionine methyltransferase dependent substitution reaction (bioalkylation) of benzo[a]pyrene in preparations of rat liver cytosol was isolated by solvent extraction and high performance liquid chromatography and its structure determined by GC/MS and NMR. The results indicate that the methyl group is introduced at the center of highest chemical reactivity (or carbon atom at which it is easiest to localize pi electrons) in the anthracene nucleus, giving rise to 6-methylbenzo[a]pyrene. These data, unequivocally demonstrate the site of substitution of the methyl group in the bioalkylation of benzo[a]pyrene. PMID- 2311195 TI - Acrolein mutagenicity in the V79 assay. AB - The mutagenicity of acrolein, allyl alcohol, glycidol and propionaldehyde was measured in V79 cells as resistance to 6-thioguanine. Acrolein was tested with and without fetal bovine serum (FBS) (10%; v/v) during the 2 h incubation period. The concentration of FBS did not affect acrolein toxicity but its mutagenicity declined as the concentration of FBS in the medium rose. Allyl alcohol (AA) was as mutagenic as acrolein (ACR). Glycidol was less mutagenic than AA and ACR. Propionaldehyde was not mutagenic at 1 microM; it was toxic at 2 microM. The data suggest that the mutagenicity of these compounds is mediated by their bifunctional nature whereas their cytotoxicity is mediated by the aldehyde function. PMID- 2311196 TI - Electroporation of normal human DNA endonucleases into xeroderma pigmentosum cells corrects their DNA repair defect. AB - Cells from patients with the cancer-prone inherited disease, xeroderma pigmentosum (XP) are known to be defective in the endonuclease-mediated incision step in excision repair of a number of different types of DNA adducts, but the molecular events responsible have not been delineated. We have previously reported isolation of two DNA endonucleases, pI 4.6 and 7.6, from normal human chromatin which recognize adducts produced by psoralen plus long wavelength ultraviolet radiation (UVA). These endonucleases are both present in XP complementation group A (XPA) cells even though these cells are hypersensitive to this type of damage. We now report that introduction by electroporation of either normal endonuclease into XPA cells restored their markedly deficient DNA repair related unscheduled DNA synthesis (UDS) to higher than normal levels following exposure to psoralen plus UVA. Introduction of XPA endonucleases into similarly treated XPA cells had little or no restorative effect on UDS. However, both normal and XPA endonucleases increased UDS in normal cells to higher than normal levels. These results indicate that XPA cells have endonucleases which can repair these adducts but which cannot function in intact cells unless a factor(s), which they lack is provided by normal cells. PMID- 2311197 TI - Chronic solvent abuse. 1. Cognitive sequelae. AB - Twelve adolescent males with a history of chronic solvent abuse were compared with 12 delinquent controls on a battery of neuropsychological tests. Toluene was the active constituent most commonly abused. Solvent abusers tended to have lower overall intelligence test scores. On the Bexley Maudsley Automated Screening Test, the solvent abusers scored significantly lower on tests involving visual processing, especially the Symbol Digit Coding test. These results are cautiously interpreted as indicating that chronic solvent abuse carries an increased risk of cognitive impairment. PMID- 2311198 TI - Chronic solvent abuse. 2. Relationship with depression. AB - Twelve adolescent males with a history of chronic solvent abuse were compared with 12 delinquent controls on a structured interview concerning their history of solvent abuse, drug and alcohol abuse, and on a self-report inventory of depression. Solvent abusers had histories of severe social and emotional deprivation, and reported higher rates of depression. This was particularly true of the most chronic abusers of solvents. These findings do not reflect any referral bias and it is concluded that the association between chronic solvent abuse and depression is a real one. Psychological, social work and psychiatric services need to take the presentation of chronic solvent abuse more seriously. PMID- 2311199 TI - Early language development and severe visual impairment. AB - Some blind children show an early facility with expressive language in advance of their true level of comprehension; children who have severely impaired vision, but use visually-directed reaching, do not. Inspection of developmental assessments of 40 blind and very severely visually impaired children with no other disability, seen at the Wolfson Centre, London, confirmed these patterns. However, a considerable number of blind children showed a lag in expressive speech relative to comprehension, which might mean first words appearing as late as 2 years of age. Later assessments of this group of children showed mixed outcomes. Further prospective research is indicated as a basis for counselling parents. PMID- 2311201 TI - Unmeasured anion during severe sepsis with metabolic acidosis. AB - It is assumed that the development of metabolic acidosis during sepsis is secondary to lactic acidosis. We assessed the composition of the anion gap during severe sepsis induced by cecal perforation in rats. In the first experiment, cardiac output, arterial blood gases, and arterial lactate were measured over a 6 hr interval in five septic rats and in five rats serving as sham-operated controls. The cardiac output decreased from 331 +/- 32 to 172 +/- 9 ml/kg/min (P less than 0.01) in the septic rats. Although the arterial lactate was increased to 2.1 +/- 0.2 mEq/L in septic rats compared to 0.8 +/- 0.1 mEq/L in sham rats (P less than 0.01), the HCO3- was decreased to 16.5 +/- 0.6 mEq/L in septic rats versus 23.8 +/- 1.10 mEq/L in sham rats (P less than 0.01). We further investigated this bicarbonate deficit in a second study in which arterial blood was sampled at 6 hr for blood gases, and plasma Na+, K+, Cl-, HCO3-, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, citrate, creatinine, albumin, and amino acids in five septic and five sham rats. The serum anion gap was calculated as [(Na(+) + K+) - (Cl(-) + HCO3-)]. The anion gap was 21.6 +/- 1.6 mEq/L in the septic animals as compared to 13.2 +/- 0.5 mEq/L in the sham animals (P less than 0.01). There were no differences in the concentration of pyruvate, beta hydroxybutyrate, acetoacetate, citrate, creatinine, albumin, or amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311200 TI - Pregnancy and antenatal care: the attitudes and experiences of Asian women. AB - Asian women living in the East End of London were interviewed in English or in their own language to assess their attitudes to and experiences of pregnancy and antenatal care and to consider some factors which may influence their experiences, especially their fluency in English. In some respects Asian women's experiences were similar to those of non-Asian women reported in other studies, e.g. similar levels of nausea and lack of tie-up between nausea and negative reactions to pregnancy. However there were also some differences, e.g. Asian women expressed greater concern about the sex of the child and about eating 'cool' foods to counterbalance the hot state of pregnancy. Asian women were good patients: they attended antenatal clinics, read the leaflets provided and about half attended antenatal classes, although some were keener than others to seek information about pregnancy and childbirth and only a quarter bought books or watched videos. Less than half of the women were living in extended families and receiving support from in-laws in the traditional way. Those living in nuclear families received support from friends, neighbours and especially husbands. There were considerable individual differences in women's reactions and experiences. Women who spoke little or no English were less knowledgeable and had lived for a shorter time in the UK than women who were fluent in English. Leaflets in languages women can read and link workers at clinics helped some women. PMID- 2311202 TI - Ranitidine compared to cimetidine in multiagent pharmacological treatment of porcine Pseudomonas ARDS. AB - The effects of two pharmacologically distinct histamine H2 receptor antagonists were studied in combination with ibuprofen (I) and diphenhydramine (D) in a porcine model of septic ARDS. Cimetidine (C) is reported as having direct oxygen radical scavenging abilities and is an inhibitor of cytochrome P-450, whereas ranitidine (R) acts solely by H2 receptor blockade. Four groups were studied: Group Ps (n = 8) received a continuous infusion of live Pseudomonas aeruginosa 5 x 10(8) CFU/ml at 0.3 ml/20kg/min, Group C (n = 6) received a control saline infusion, and the treatment groups received I (12.5 mg/kg) and D (10 mg/kg) in combination with either C (150 mg, CID, n = 6) or R (25 mg, RID, n = 5) given at 20 and 120 minutes after the onset of Ps. Pulmonary (PAP) and systemic (SAP) arterial pressures, cardiac index (CI), PaO2, thermal cardiogreen extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux (slope index, SI) were measured. Ps infusion produced significant (p less than 0.05) cardiovascular collapse, hypoxemia and increased EVLW and SI. Both CID and RID temporarily reversed pulmonary arterial hypertension and maintained PaO2, EVLW, SAP and CI at control levels throughout the study, and significantly improved SI at 180 min. These results suggest that cimetidine and ranitidine act in this combination therapy primarily as H2 receptor antagonists. PMID- 2311203 TI - Net inotropic plasma activity in canine hypovolemic traumatic shock: low molecular weight plasma fraction after prolonged hypotension depresses cardiac muscle performance in vitro. AB - Numerous studies report controversial results about the occurrence and role of cardiodepressant substances in various forms of circulatory shock. We investigated the net inotropic effect of the low molecular weight fraction (mol wt less than or equal to 1,000) of plasma in prolonged canine hypovolemic traumatic shock using an in vitro guinea pig papillary muscle assay (isotonic mode). The shock plasma fractions (ultrafiltrates) after 4 hr of hypotension (mean arterial blood pressure 40-50 mm Hg) and immediately post-reinfusion significantly depressed papillary muscle function (P less than .02). The extent of papillary muscle shortening was decreased by 49.5 +/- 9.9% in pre- and 50.6 +/ 10.0% in post-reinfusion plasma ultrafiltrates (mean values +/- standard error of the mean; n = 6 shock experiments). In contrast, both the plasma ultrafiltrates from ten non-anesthetized healthy dogs and the control ultrafiltrates obtained prior to onset of shock in the experiments (-6.4 +/- 2.6; n = 6) induced no significant change of the in vitro performance of papillary muscle contraction. These results were achieved with plasma fractions in which ionized calcium and pH were adjusted to concentrations equivalent to the bioassay solution. Lactate acidosis and severe hypoglycemia (1.97 +/- 0.43 mM post reinfusion) occurred in the shock experiments. Lack of energy substrate (glucose) was not responsible for the in vitro depression. Four depressive shock ultrafiltrates with glucose concentrations adjusted to control ultrafiltrate levels induced a 66.6 +/- 8.8% decrease in the extent of papillary muscle shortening. These results suggest that the possible occurrence of high net negative inotropic activity in plasma, especially just post-reinfusion, may play a role in the pathogenesis of irreversible circulatory shock. PMID- 2311204 TI - Protective effects of a novel 21-aminosteroid during splanchnic artery occlusion shock. AB - We investigated the effects of a novel, non-glucocorticoid 21-aminosteroid, U74006F, in the pathogenesis of splanchnic artery occlusion (SAO) shock in rats. Pentobarbital-anesthetized (40 mg/kg) rats were subjected to 40 min of occlusion of both the celiac and superior mesenteric arteries followed by reperfusion, which resulted in a severe shock state characterized by a markedly lower mean arterial blood pressure (MABP) and a survival time of 40-80 min post-reperfusion. In contrast, infusion of U74006F (22.5 mg/kg) during the occlusion period resulted in a significantly higher MABP following reperfusion which prolonged survival (117 +/- 3 min vs. 66 +/- 10, P less than .01) compared to those rats receiving only the vehicle for U74006F (0.002 N HCl). Hematocrits measured at the end of each experiment were significantly lower in the treated shock rats compared to the untreated group (55.7 +/- 1.8 vs. 63.0 +/- 1.7, P less than .01). SAO shock rats treated with U74006F also exhibited significantly attenuated plasma accumulation of cathepsin D (P less than .05) and myocardial depressant factor (MDF) (P less than .01). Six of 7 SAO shock rats treated with U74006F survived for 120 min following reperfusion, while none of 7 SAO shock rats given the vehicle survived for 120 min (P less than .01). These results suggest that U74006F has therapeutic utility in SAO shock. PMID- 2311205 TI - Improved biological properties of synthetic distearoyl phosphatidyl choline-based liposome in the conscious rat. AB - We have previously produced and tested a liposome preparation based on hydrogenated soy lecithin (HSL-L) for the purpose of designing blood replacement in the form of liposome encapsulated hemoglobin (LEH). While these liposomes had acceptable physicochemical properties which addressed many of the desirable characteristics of "artificial blood," they produced hypotension, hemoconcentration, and thrombocytopenia when administered to rats. The following studies present improved synthetic distearoyl phosphatidylcholine-based liposomes (sDSPC-L) which were compared to the HSL-L for their biological effects in the conscious normovolemic rat (n = 6 - 11). HSL-L induced hypotension (-25 +/- 3 mmHg, P less than 0.01), tachycardia (+88 +/- 11 beats/min, P less than 0.01), decrease in cardiac index (-33 +/- 4%, P less than 0.01), and elevation of the total peripheral resistance index (+0.450 +/- 0.003 mmHg/ml/min/kg, P less than 0.01). The hematologic responses to HSL-L were: leukocytosis (+6,070 +/- 1,064/microliters, P less than 0.01), hemoconcentration (+4.0 +/- 0.1%, P less than 0.01), 0.01), and thrombocytopenia (-160 +/- 18 X 10(3)/microliters, P less than 0.01). Plasma thromboxane B2 (TXB2) was elevated to 30.4 +/- 5.6 pg/100 microliters (P less than 0.01). In contrast, the only effects induced by sDSPC-L were slight tachycardia (+37 +/- 9 beats/min, P less than 0.05) and a marginal increase in plasma TXB2 to 9.7 +/- 3.3 pg/100 microliters (P less than 0.05). All effects, except for those related to cardiac output and peripheral resistance, were transient. These data underscore the importance of pure synthetic DSPC in improving the biological effects of liposomes and suggest sDSPC-L as a promising vehicle for encapsulating hemoglobin. PMID- 2311206 TI - Airway aspiration of hydrochloric acid in sheep. AB - We have compared the effects of aspiration of 2.5 ml/kg of 0.1 N hydrochloric acid (HCl) on groups undergoing normal saline aspiration (2.5 ml/kg) and a sham control in unanesthetized sheep with chronic lung lymph fistula for up to 148 hr. Significant changes in pulmonary lymph flow and cardiopulmonary variables occurred in the airway acid group within the first 48 hr, as compared to saline and sham control. In the HCl group lymph flow increased from a baseline of 8.5 +/ 1.5 to 21.8 +/- 3.0 ml/hr (mean +/- SEM) at 2 hr. Pulmonary vasoconstriction occurred at this time with significant elevations of lymph thromboxane B2 from a baseline of 400 +/- 11 to 2,090 +/- 690 pg/ml. During the early acid aspiration phase products of lipid peroxidation were noted to increase from 0.29 +/- 0.03 to 0.81 +/- 0.17 absorbance units. Associated with elevated lymph flow was a significant drop in cardiac index in the airway-acid-aspirated group (6.59 +/- 0.52 to 5.53 +/- 0.36 L/min/m2) and a rise in bronchial blood flow from 9.8 +/- 1.7 to 63.7 +/- 8.9 ml/min. These data suggest that a moderate airway acid injury created by 2.5 ml/kg of HCl results in acute pulmonary damage with the release of several potential mediators which may be responsible for the observed effects. The long-term acid-injured animals survived for up to 1 week following the aspiration procedure with evidence of resolution of lung damage by wet-weight dry weight evaluation of lung (normal lab control = 4.0 +/- 0.2, and 148 hr after acid = 4.5 +/- 0.3) and microscopic evidence of minimal persistent injury. These data document the pulmonary damage and repair resulting from airway acid instillation. PMID- 2311207 TI - Radioimmunoassay of type I collagen that mainly detects degradation products in serum: application to patients with liver diseases. AB - This radioimmunoassay for type I collagen mainly detects degradation products of the molecule in human serum samples. Type I collagen antigenicity in serum can be separated into two peaks by gel-filtration chromatography. The larger form represents collagen molecules (as shown by immunoblotting experiments), and (or) type I collagen with aminoterminal propeptide or intact procollagen molecules. The smaller form, the exact nature of which is not known, is quantitatively the principal antigenic form and is derived from degradation of type I collagen. The concentration of type I collagen in serum is increased mainly in cirrhotic patients, with or without active liver disease, but also somewhat in alcoholic patients without cirrhosis. PMID- 2311208 TI - Muscle enzymes and isoenzymes in Emery-Dreifuss muscular dystrophy. AB - Emery-Dreifuss muscular dystrophy (EDMD) is a rare X-linked muscular dystrophy. Creatine kinase (CK) activity usually is increased in serum of affected males, but results for aldolase and lactate dehydrogenase (LD) in serum have been inconsistent, as have those for CK in carrier females. There have been few studies of CK-MB or LD isoenzyme-1 (LD-1) in EDMD. We measured CK, CK-MB, LD, LD 1, and aldolase activity in sera of 84 members of two large families with EDMD. DNA analysis had been carried out on all subjects. Although CK, LD, and aldolase activities were significantly increased in affected males, CK activity was the most consistently increased and was the least subject to artifactual increases. Mean CK-MB in serum was mildly increased, but LD-1 was within the normal reference interval, suggesting that CK-MB is increased in skeletal muscle in EDMD, as has been found in other forms of dystrophy. CK decreased with age in affected males. We saw no significant increases of muscle enzymes or isoenzymes in 33 EDMD carriers studied, of whom 19 were obligate carriers and 14 had been identified by DNA analysis. PMID- 2311209 TI - Changes in laboratory results for cancer patients treated with interleukin-2. AB - The systemic administration of interleukin-2 (IL-2) can lead to significant antitumor responses in some patients with metastatic cancer in whom standard therapy has failed. A limitation of this immunotherapy is the toxicity associated with IL-2 infusion. To assess toxicity, we determined aspartate aminotransferase (AST; EC 2.6.1.1), alanine aminotransferase (ALT; EC 2.6.1.2), gamma glutamyltransferase (GGT; EC 2.3.2.2), lactate dehydrogenase (LD; EC 1.1.1.27), alkaline phosphatase (ALP; EC 3.1.3.1), creatine kinase (CK; EC 2.7.3.2), total bilirubin (TBI), direct bilirubin (DBI), creatinine, urea nitrogen, and C reactive protein in serum from 21 patients before and during five consecutive days of IL-2 treatment. Ten patients were followed for an additional five days after the end of IL-2 therapy. The IL-2 infusion caused liver toxicity and prerenal azotemia, as evidenced by significant increases (P less than 0.05) of all analytes except CK by day 1. There was a progressive increase in the results (except CK) for these tests until IL-2 treatment was stopped. Seven tests related to liver function (AST, ALT, GGT, LD, ALP, DBI, and TBI) showed increases, but the test results indicated significant improvement and moved toward the baseline value five days after the end of IL-2 therapy. Concentrations of creatinine and urea nitrogen in serum were normal three days after the cessation of IL-2 therapy. PMID- 2311210 TI - Ultraviolet-absorbing organic anions in uremic serum separated by capillary zone electrophoresis, and quantification of hippuric acid. AB - Organic anions accumulated in blood serum of patients with chronic renal failure were separated by a novel technique: closed-system capillary zone electrophoresis (CZE) in a pH6 carrier-electrolyte system. Hippuric acid (HA), p-hydroxyhippuric acid, and uric acid were identified by their co-elution with standards prepared in ultrafiltered normal serum and by comparison with the corresponding ultraviolet-detected peaks positively identified in the HPLC analyses. Analysis time for the entire profile is 8 min. Repeatabilities (CVs) of CZE migration times and peak areas of the three acids in serum samples were about 0.7% and 6%, respectively. We quantified HA in 10 ultrafiltered uremic serum samples and compared results with those by a previously described HPLC procedure. The very good agreement further supports the identification of hippuric acid. Accuracy and precision of the CZE method were similar to those for the HPLC gradient-elution method, but analysis time for HA (8 min) is much less than by HPLC (90 min). Our technique is very suitable for selective, rapid analysis for (ultraviolet absorbing) anionic constituents in ultrafiltered uremic serum, without any sample pretreatment. PMID- 2311211 TI - Rapid, robust method for measuring low concentrations of albumin in urine. AB - We describe a rapid particle-enhanced turbidimetric immunoassay for albumin in urine. Intra- and interassay CVs were less than 5% and less than 10%, respectively, the detection limit is 2 mg/L, and the working range extends to 200 mg/L. Mean analytical recovery of albumin added to centrifuged urines was 100% (SD 10.6%), and, when results were compared with those by the Pharmacia RIA, the correlation coefficient was 0.99. The working reagents are stable for at least six months; thus this assay is suited for both batch and urgent analysis. PMID- 2311212 TI - Manganese content of the cellular components of blood. AB - We measured the manganese content of whole blood, plasma, platelets, mononucleated cells, polymorphonucleated cells, and erythrocytes. Platelets and blood cells were separated from whole blood by use of discontinuous gradients of colloidal polyvinylpyrrolidone-coated silica (Percoll), and their manganese content was measured by Zeeman graphite furnace atomic absorption spectrophotometry, after digestion with nitric acid and hydrogen peroxide. Erythrocytes account for about 66% of the manganese in whole blood, whereas the "buffy coat"--platelets and leukocytes--accounts for about 30%. The "buffy coat" components turn over more rapidly than do erythrocytes, so their manganese content may better indicate the body's manganese status. PMID- 2311213 TI - A simulation study of the Westgard multi-rule quality-control system for clinical laboratories. AB - A particular version of the Westgard-Barry-Hunt-Groth (Westgard) multi-rule quality-control system is studied by Monte Carlo simulation. The principal focus is on the amount of distortion in the working power curve caused by skewness in the distribution of analyte measurements. The effect of using only the first two rejection modes of the Westgard system is also studied. PMID- 2311214 TI - Neutral ionophore-based selective electrode for assaying the activity of magnesium in undiluted blood serum. AB - The concentration of free, ionized magnesium in undiluted blood serum can be determined potentiometrically with a new magnesium-selective carrier in polymeric membrane electrodes (by weight 66% plasticizer, approximately 33% polyvinyl chloride and approximately 1% ionophore). However, discrimination of calcium by the new ionophore-added membrane is not sufficient to keep calcium interference to less than 1%. To correct for the interference by calcium, we determine the calcium activity of the serum sample with a calcium-selective electrode and calibrate the magnesium-selective electrode with standard solutions containing calcium in the concentrations found. In this way we determined the free ionized magnesium in five plasma samples from five different persons and found it to be within the range expected for magnesium in undiluted serum. PMID- 2311215 TI - Concentrations of free thyroxin and free triiodothyronine in serum of patients with thyroxin- and triiodothyronine-binding autoantibodies. AB - Between 1982 and 1989 we identified 47 subjects with spuriously increased concentrations of free thyroxin (FT4) or free triiodothyronine (FT3) related to autoantibody interference in analog FT4 and (or) FT3 methods. The incidence of autoantibody interference observed during one year (1988) was 1 in 2460. In the subjects identified, 51% and 11%, respectively, showed an increased binding of radiolabeled T4 or T3 analog alone; 38% had an increased binding of both. Of 36 patients tested, 71% had autoantibodies to thyroglobulin and microsomal fraction of the thyroid, 19% to microsomal fraction alone, and 9.5% to thyroglobulin alone. In eight subjects, spuriously increased FT4 concentrations were reported with the following FT4 methods (in decreasing order of interference): Coat-A Count, Amerlex-M, Amerlite, Seria, Magic Lite, Amerlex-MAB. In the same eight subjects, Amerlex-M and Seria reported spuriously increased concentrations of FT3. PMID- 2311216 TI - Rapid, simple enzymatic assay of free L-fucose in serum and urine, and its use as a marker for cancer, cirrhosis, and gastric ulcers. AB - We devised a kit for use with automated analyzers, for assay of urinary free L fucose by means of a newly isolated L-fucose dehydrogenase (EC 1.1.1.122), and we measured L-fucose in healthy subjects, cancer patients, and patients with other diseases. It takes 10 min to complete one assay. Absorbance and L-fucose concentration were linearly related up to at least 3.0 mmol/L, analytical recovery was 90-104%, and intra- and interassay coefficients of variation were less than 4.2% and 7.8%, respectively. The concentrations of L-fucose, corrected for creatinine, were significantly higher than those in healthy subjects in nine of 18 patients with gastric ulcers, 19 of 21 patients with cirrhosis of the liver, and 206 of 366 patients with some type of cancer, reflecting a changed L fucose metabolism. Because urine specimens are analyzed and the test is rapid and inexpensive, this method may be suitable for mass screening for some kinds of cancer, cirrhosis, and gastric ulcers. PMID- 2311217 TI - Distribution of trace elements in the lipid and nonlipid matter of hair. AB - We studied the effect of lipid removal on the concentrations of 13 trace elements measured in human hair. We used a pooled specimen of hair from a barber shop, initially washed with de-ionized water, with ultrasonic cleaning, then analyzed for Ca, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, Si, Sr, and Zn with use of an inductively coupled plasma emission spectrometer. The lipid was removed by Soxhlet extraction with ethanol, and the hair was re-analyzed. We found several elements present in a relatively large proportion (greater than 20%) in the lipid fraction, mainly Na, K, Ca, Mg, Ni, and Sr. We suggest that removal of part or all of the lipids from hair by using detergents or other lipid-removing solvents for washing may account for the variability in data on elements in hair reported by different laboratories, and that those elements largely present in the lipid fraction are the result of environmental exposure, whereas those retained in the hair fiber after lipid removal can be attributed to nutritional and clinical aspects. We believe that such determination of the distribution of elements may help validate the use of hair in assessing trace elements in the body. PMID- 2311218 TI - Suppression of endogenous cortisol for evaluating pharmacodynamics of prednisolone in early allograft rejection in renal transplantation. AB - Concentrations of endogenous cortisol were examined in 34 kidney-transplant recipients by improved "high-performance" liquid chromatography. Ten recipients were treated with prednisolone and azathioprine, the others with prednisolone and cyclosporine. Peripheral serum samples were collected just before transplantation, daily for two weeks after the transplant, weekly until discharge for about two months, and then monthly or occasionally. Mean (+/- SD) cortisol concentrations, initially 145 +/- 87 micrograms/L, decreased immediately to 5.93 +/- 5.11 micrograms/L after transplant, remained at almost these same values for two months, and then swiftly increased to 51 +/- 59 micrograms/L by 1000 days. Cortisol concentrations within the period characterized by a cumulative dose of prednisolone at 300-700 mg were correlated significantly with the presence or absence of acute allograft rejection; patients with cortisol greater than 4 micrograms/L had a higher risk of rejection. The majority of stable patients showed cortisol concentrations between 1 and 4 micrograms/L throughout the cumulative prednisolone period characterized above. Concentrations less than 1 microgram/L after high-dose administration of methylprednisolone were accompanied by severe lung infection. We conclude that suppressed concentrations of endogenous cortisol, as assessed by highly specific HPLC, might provide a basis for predicting the therapeutic efficacy and adverse effects of prednisolone. PMID- 2311219 TI - Response of various indices of iron status to acute iron depletion produced in menstruating women by low iron intake and phlebotomy. AB - We investigated response sensitivities of indices of iron status to controlled iron depletion and repletion in 11 premenopausal women. The women were depleted of storage iron (as reflected by serum ferritin) through a combination of a low iron diet and phlebotomy. They then consumed a diet containing 13.7 mg of iron per 2000 kcal, supplemented with either ascorbic acid or placebo (for 5 1/2 weeks) and a daily 50-mg iron supplement (for the subsequent 17 days). The relative sensitivities of different indices for detecting iron depletion were as follows: ferritin greater than % transferrin saturation greater than plasma iron greater than hemoglobin greater than hematocrit greater than zinc protoporphyrin (ZnPP) and erythrocyte protoporphyrin (EP). Ascorbic acid treatment during repletion, before iron supplementation, significantly (P less than 0.05) affected changes in hemoglobin, ZnPP, ZnPP/heme, and EP/heme. Changes in heme synthesis evidently do not occur until iron stores are depleted and, conversely, during iron repletion hematopoiesis must be satisfied before iron stores, as reflected by ferritin, increase. Thus, the use of only one index of iron status is of limited value for detecting iron depletion. PMID- 2311220 TI - Immobilization of immunoglobulins onto surface-treated and untreated polystyrene beads for radioimmunoassays. AB - The immunoreactivity of anti-triiodothyronine (anti-T3) IgG, pretreated at acidic pH and adsorbed onto polystyrene beads, was significantly greater than that determined for native anti-T3 IgG immobilized at optimum pH 3.5. Acidic-pH pretreated IgG, adsorbed at pH 7.0 onto ethanol-treated beads, had less immunoreactivity than that on untreated beads and gave values similar to those of native IgG adsorbed onto activated beads at pH 9.6. The rate of immobilization onto treated beads was significantly greater than onto untreated ones, and the binding was reproducible (intra- and inter-batch coating CV, 3.7-4.6% and 7.2%, respectively) and very resistant to successive washings. A post-washing incubation in 10 mg/L bovine serum albumin solution was required to eliminate the decreased immobilized immunoreactivity caused by some washing reagents. For solid phase radioimmunoassays of T3, 40% less antibody was needed when acidic-pH pretreated IgG was adsorbed onto untreated beads or when native IgG was adsorbed onto ethanol-treated beads, in comparison with native IgG adsorbed onto untreated beads. Results and assay characteristics with such beads were comparable with results for solid-phase and liquid-phase polyethylene glycol assay of T3. PMID- 2311221 TI - Sensitive time-resolved fluorescence immunoassay of somatotropin in serum. AB - We describe a new "sandwich"-type non-isotopic immunoassay for human somatotropin (GH, growth hormone) in serum. In the assay, GH is captured by a monoclonal antibody immobilized in a white microtiter well and simultaneously reacted with a second biotinylated monoclonal antibody. The degree of binding of biotinylated antibody, which increases with increasing amount of GH in the sample, is quantified by adding streptavidin labeled with the europium chelate of 4.7 - bis(chlorosulfophenyl) - 1.10 - phenanthroline - 2.9 - dicarboxylic acid. The fluorescent complex on the solid phase is then measured by excitation at 337.1 nm (nitrogen laser) and monitoring the emission at 615 nm in a gated fluorometer/analyzer. The proposed procedure has short incubation times (less than 4 h protocol), uses only 25 microL of serum per microtiter well, and gives precise and accurate results. The method was clinically evaluated with samples obtained from pediatric patients undergoing investigation for growth abnormalities and from a patient with acromegaly. PMID- 2311222 TI - Rapid solid-phase immunoassay for 6-keto prostaglandin F1 alpha on microplates. AB - We describe, for the measurement of 6-keto prostaglandin F1 alpha in biological media, a solid-phase immunoassay with immobilized antibodies that requires a total processing time of less than 2 h with hands-on time less than 30 min for 40 samples. The method combines the convenience of the microplate format with the sensitivity of radiolabeled prostaglandin derivatives as tracers in a competitive immunoassay. The intra- and interassay variations at 50% displacement of the radiolabeled prostaglandin derivative as tracer were 9.0% and 11.8%, respectively. At 50% displacement of the radiolabeled tracer, the sensitivity is about 20 pg per well. Optimal incubation time is between 60 and 90 min. Nonspecific binding was less than 1% if about 8 pg of tracer (approximately 25,000 counts/min per well) was used. Inhibition curves of samples in different dilutions were parallel to standard curves. The variation of bound radiolabeled prostaglandin derivative within the wells of one microplate (n = 96) was less than 3%. Human plasma samples and medium from tissue culture assayed for 6-keto prostaglandin F1 alpha correlated well with results obtained with a solid-phase assay based on use of magnetic particles (r = 0.99, n = 24 for culture-medium samples; r = 0.99; n = 26 for plasma samples. PMID- 2311223 TI - Electron-capture gas chromatography as a sensitive method for measuring subnanogram amounts of cholesterol in saliva and urine. AB - This is a sensitive method, suitable for measuring subanogram amounts of cholesterol. Cholesterol and the internal standard, epicoprostanol (5-beta cholestan-3-alpha-ol), are derivatized with pentafluorobenzoyl chloride and detected by electron-capture gas chromatography. The pentafluorobenzoyl esters of cholesterol and the internal standard are easily formed and possess excellent chromatographic and electron-capturing properties. The lower limit of detection of the method, approximately 100 pg injected, is about 500-fold as sensitive as chromatographic methods involving flame-ionization detection. Within-day and between-day coefficients of variation were 4.2% and 8.2%, respectively, for determinations of a urinary cholesterol concentration of 570 micrograms/L (1.47 mumol/L). Such sensitivity permits analysis for cholesterol in (e.g.) physiological fluids, tissue samples, and cell cultures that contain very low concentrations of cholesterol. PMID- 2311224 TI - Basement membrane-related and type III procollagen-related antigens in serum of patients with chronic viral liver disease. AB - To assess the significance of serum basement membrane- and type III procollagen related antigens in reflecting the degree of liver fibrosis, we measured radioimmunologically the concentrations of 7S collagen, laminin fragment P1, and the aminoterminal propeptide of type III procollagen (P-III-P) in serum from 48 patients with chronic viral liver disease: chronic persistent hepatitis (9), chronic active hepatitis (13), chronic active hepatitis with lobular disorganization (17), and liver cirrhosis (9). Concentrations of 7S collagen, laminin P1, and P-III-P in serum were increased in respectively 92%, 69%, and 77% of the patients with both chronic active hepatitis with lobular disorganization and liver cirrhosis. Concentrations of 7S collagen and laminin P1 in serum correlated well (r = 0.65, P less than 0.001, and r = 0.55, P less than 0.001, respectively) with the histological grade of liver fibrosis, whereas P-III-P correlated only weakly (r = 0.33, P less than 0.05). Evidently, measurement of serum 7S collagen is a reliable noninvasive test for detection of fibrosis in chronic viral liver disease. PMID- 2311225 TI - Radioimmunological determination of total thyroxin by antibodies immobilized on polystyrene tubes coated with styrene-maleic anhydride copolymers. AB - In this new technique for preparing activated polystyrene tubes for assay of human thyroxin (T4) we coated plastic with styrene-maleic anhydride copolymers. The quantity of antibodies immobilized on these tubes was considerably greater than on non-activated polystyrene tubes, and the time required for immobilization was shortened. Calibration curves were plotted, and determination of total T4 in 200 serum samples confirmed the expected increase in sensitivity as compared with a commercial (Gammacoat) method. The manufacturing procedure is simple and could easily be automated. Thus, such copolymer-coated tubes constitute an advantageous and reliable component in the assay of total T4 that can be used to improve the sensitivity of this and various other radioimmunological determinations. PMID- 2311226 TI - Flocculation of serum lipoproteins with cyclodextrins: application to assay of hyperlipidemic serum. AB - We describe the complexation of isolated and native lipoproteins by natural macrocyclic polymers of glucose ("cyclodextrins"). Treatment of serum with cyclodextrin produces an immediate flocculation of the lipoproteins. The formation of cyclodextrin-lipoprotein complexes was evident on agarose electrophoresis gels. The concentration-dependent ability of alpha-cyclodextrin to precipitate chylomicrons and very-low-, low-, and high-density lipoproteins was used for clarifying lipemic serum. Results for normal and lipemic patients' specimens for some routinely measured analytes showed a good correlation between cyclodextrin treatment and ultracentrifugation. Unlike the use of organic solvents or ultracentrifugation, the proposed system provides a simple, mild, non hazardous, and effective means for removing interfering lipid particles from biological specimens. PMID- 2311227 TI - Liquid-chromatographic determination of amiodarone and N-desethylamiodarone in serum. AB - We have developed a stable and simple normal-phase liquid-chromatographic method for simultaneously measuring amiodarone and its metabolite, N-desethylamiodarone, within 8 min. The chromatographic system consists of a 15 cm x 3.9 mm Waters "Resolve" silica column and a mobile phase of ammonium sulfate (17 mmol/L, pH 6.8) and methanol (8/92 by vol), pumped at 1.8 mL/min and monitored at 254 nm. After 250 microL of serum is mixed with 100 microL of 0.36 mol/L NaH2PO4, 100 microL of the internal standard solution (L8040, 6 mg/L), and 200 microL of isopropyl ether, the mixture is vortex-mixed and centrifuged. Fifty microliters of the organic layer is injected onto the column. Relative recovery was 100% over the assay range of 0.1 to 20.0 mg/L for both compounds. Within-run and total (day to-day) CVs were 3% and 7% for amiodarone and 5% and 8% for N-desethylamiodarone, respectively. PMID- 2311228 TI - Effect of serum lyophilization on the rate constants of enzymatic methods for measuring cholesterol. AB - We determined the equilibrium absorbances and rate constants for two enzymatic methods, aca (DuPont) and RA-1000 (Technicon), used in determining cholesterol in reconstituted lyophilized serum. The lyophilized materials included two serum pools, three control materials, a College of American Pathologists' survey material, and Standard Reference Material no. 909. We calibrated the reagents with aca standards for cholesterol (DuPont). The difference in the mean concentrations of cholesterol (aca - RA-1000) was -0.09 g/L overall and was not statistically significant by analysis of variance. The mean rate constant for all materials was 0.23 min-1 for the aca and 1.42 min-1 for the RA-1000, significantly different (P less than 0.001). Lyophilization causes lower results for the aca method than for the Ra-1000, because the reaction rate for the aca method is slower and has not reached equilibrium when the final absorbance reading is made. PMID- 2311229 TI - Improved sample preparation in determination of urinary metanephrines by liquid chromatography with electrochemical detection. AB - In this relatively simple procedure for extracting metanephrines from urine, after an internal standard (4-hydroxy-3-methoxybenzylamine in 1 mmol/L HCl) is added, the sample is hydrolyzed in a boiling water bath, then treated with ammonia and alumina. Excess ammonia is removed under reduced pressure and the sample is applied to a 1-mL Bond Elut SCX column, which is washed, and metanephrines and internal standard are eluted with 0.5 mmol/L sodium acetate/acetonitrile (3/1 by vol). Of this elute, 5 microL is injected into a 15 cm x 4.6 mm (i.d.) column packed with 5-microns octadecylsilyl silica particles, which is eluted with a mobile phase containing tetramethylammonium perchlorate. Peaks are detected coulometrically at +0.28 V. In the resulting chromatogram, metanephrines give sharp peaks, well resolved from peaks for solvent and internal standard. There are no extraneous peaks for catechols or mono-oxygenated phenylethylamines. Results correlated well (r = 0.999, n = 13) with those by earlier described liquid-chromatography. PMID- 2311230 TI - Adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood compared for clinical evaluation of patients with disorders of calcium metabolism. AB - We report results for adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood from 183 patients with disorders of calcium metabolism (primary hyperparathyroidism, secondary hyperparathyroidism of malabsorption, primary hypoparathyroidism, Paget's disease, acromegaly, hypercalcemia of malignancy, osteoporosis, sarcoidosis, idiopathic hypercalciuria, and familial hypocalciuric hypercalcemia). The correlation and the equation for the linear regression between adjusted ionized calcium (y) and actual ionized calcium (x) were y = 1.011x + 0.005 mmol/L, r = 0.992, Sy,x = 0.021 mmol/L. Results were similar within each diagnostic group. Consistent agreement between adjusted and ionized calcium was observed in 96.7% of patients representing a variety of the most frequently encountered disorders of calcium metabolism. Thus we find adjusted ionized calcium to be as useful as actual ionized calcium for evaluation of patients with such disorders. Adjusted ionized calcium may therefore also be a logical choice for establishing agreement between laboratories for reference intervals in healthy adults. PMID- 2311231 TI - Sample evaporation and its impact on the operating performance of an automated selective-access analytical system. AB - In a series of gravimetric and analytical experiments I measured how much analytical error is ascribable to sample evaporation during routine operation of the Dimension analytical system. This error, a time-dependent function, is related to the volume of liquid placed in either a 0.5- or 2.0-mL cup and whether the cup is capped. For the 0.5-mL cups, analytical error at a 4-h residence time ranged from 12% to 16% (uncovered) to 8% to 13% (covered), whereas errors for the 2.0-mL cup ranged from 6% to 10% (uncovered) to 2% to 5% (covered). To minimize evaporative loss, I recommend (a) protecting the surface areas of the samples, (b) using larger samples, and (c) minimizing the time that a sample is in its cup before and during analysis. PMID- 2311232 TI - Optimal sites and depths for skin puncture of infants and children as assessed from anatomical measurements. AB - Postmortem measurements were made of distances from skin surface to underlying bone/cartilage on 43 children (up to 8 y old; weights from 0.7 to 26.4 kg) to determine optimal sites and lengths of lancet tips for skin puncture of the heel, great toe, and middle finger. For measuring depths, a needle-like probe was devised that minimized disfigurement. As long as the infant's heel was available for puncture prior to callus formation (to about six months), it offered the greatest depth and the bone/cartilage of the lateral/medial sites was considerably deeper than posterior sites. At age six months, the mean distance of skin surface. At age six months, the mean distance of skin surface to bone/cartilage in the middle finger was 2.5 mm, the lower 95% prediction interval being 1.5 mm. Lengths of lancet tips for finger puncture should therefore be made less than 1.5 mm. To get the desired volumes of blood, a compromise must be reached between depth and width of the lancet tip. PMID- 2311233 TI - 3-Methylhistidine determined in plasma by "high-performance" lipid chromatography. AB - In this fully automated method for determination of 3-methylhistidine (3MH) in plasma we use precolumn derivatization with o-phthaldialdehyde and subsequent separation by HPLC. Total analysis time is 36 min, and peak areas measured vary linearly with the amount of analyte injected, over the range of 0 to 20 pmol of 3MH (R2 = 0.995), with a coefficient of variation (CV) of 1.6%. The method is reliable, accurate, inexpensive, and at least 1000-fold more sensitive than conventional ion-exchange chromatography with ninhydrin. Because of its sensitivity, the method can be used to estimate venous-arterial differences. In four human volunteers the plasma 3MH concentration varied between 4.97 and 6.08 mumol/L, and the difference between "arterialized" and femoral venous blood for 3MH varied between 0.09 and 0.47 mumol/L. PMID- 2311234 TI - Alpha 1-acid glycoprotein decreases recovery of total protein in urine when trichloroacetic acid is used to precipitate the proteins. AB - Total urine protein was measured in 132 samples by an automated benzethonium chloride method and the Ponceau-S/trichloroacetic acid (PS/TCA) method. Of these, 27% gave a result 0.1 g/L or more higher by the benzethonium chloride method. Of this 27%, most contained an abnormally high concentration of the acute-phase reactant, alpha 1-acid glycoprotein. By assaying urine containing added alpha 1 acid glycoprotein and albumin, we found that alpha 1-acid glycoprotein causes the PS/TCA method to underestimate the total urine protein concentration, whereas the benzethonium chloride method is unaffected. Not all urinary albumin was precipitated by TCA when alpha 1-acid glycoprotein was present. Therefore, protein methods in which trichloroacetic acid is used as a concentrating step before the assay will underestimate total urine protein when the concentration of alpha 1-acid glycoprotein is high. PMID- 2311235 TI - Hyperparathyroidism in a patient with Wilson's disease. AB - We describe hyperparathyroidism in an 18-year-old man with Wilson's disease--the first report in the English literature of the simultaneous occurrence of these two conditions. PMID- 2311236 TI - Quantification of high-density-lipoprotein cholesterol in plasma from hamsters by differential precipitation. PMID- 2311237 TI - Identification and treatment of hypomagnesemia and hypokalemia in patients receiving digoxin. PMID- 2311238 TI - Fecal alpha 1-antichymotrypsin in inflammatory bowel diseases. PMID- 2311239 TI - Microdetermination of cutaneous apoprotein B: application to screening of coronary heart disease. PMID- 2311240 TI - Determination of citrate in urine by simple direct photometry. PMID- 2311241 TI - Pseudohypernatremia and increased HCO3- in serum preserved with sodium azide. PMID- 2311242 TI - Apparently increased plasma parathyrin values after total parathyroidectomy and parathyroid tissue autograft. PMID- 2311243 TI - Further equipment recommendations for measuring the activity of creatine kinase. PMID- 2311244 TI - Tests for occult blood: a clarification. PMID- 2311245 TI - More on stability of lithium in clotted blood. PMID- 2311246 TI - Sugar-chain multiformity of human carcinoembryonic antigen: difference between normal and tumor-associated subfractions. PMID- 2311247 TI - Assessment of two anion-exchange resins for direct use in the screening method for urinary porphobilinogen. PMID- 2311248 TI - Evaluation of assay linearity. PMID- 2311249 TI - Third Alkaline Phosphatase Symposium. La Jolla Cancer Research Foundation, February 1-3, 1989. PMID- 2311250 TI - Purification and some properties of the fast migrating alkaline phosphatase in FL amnion cells (the Kasahara isoenzyme) and its cDNA cloning. AB - One of two main FL-amnion cell alkaline phosphatase (AP), the fast migrating one (FL-APF) has been reported to be identical to Kasahara isoenzyme (K.I.), which occurs preferentially in sera of patients with primary hepatoma. We purified FL APF of which the apparent molecular weight was 135,000 by gel filtration, and that of the subunit was 62,000 on SDS/PAGE, indicating homodimeric structure of FL-AL-APF. FL-APF was found to react with monoclonal antibody against adult intestinal AP, but not with monoclonal antibody to placental AP. We isolated FL APF cDNA clone from FL-amnion cells, of which cDNA was 2525 base pairs in length. Nucleotide sequence of the coding region and the 3' untranslated region was identical to the sequence of human adult intestinal AP cDNA. But the untranslated region of the 5' end of the isolated clone was slightly longer than that of intestinal AP. Hence, FL-APF (K.I.) may occur by altered glycosylation of intestinal AP. PMID- 2311251 TI - Cloning and characterization of a cDNA encoding alkaline phosphatase in mouse embryonal carcinoma cells. PMID- 2311252 TI - Allelic and ectopic polymorphisms in human placental alkaline phosphatases: sugar chain heterogeneities. PMID- 2311253 TI - Alkaline phosphatase of rat intestinal lymph: its characterization and the effect of fat administration. AB - Biological characteristics of alkaline phosphatase (ALP) from rat intestine were compared among four various fractions (brush border, cytosol, luminal and lymph) to clarify the source and route of ALP appeared in intestinal lymphatics. ALP of each fraction had the same Km values and the same heat stability and all were of intestinal type. However, lymph and cytosol ALP showed similar affinity to three kinds of lectins and were distinct from membrane and luminal ALP. On polyacrylamide gel electrophoresis (PAGE), there seems to be two types of charge isomers of intestinal ALP, namely brush border type and lymph type. On sodium dodecyl sulfate (SDS)-PAGE, the molecular weight of principal band for each form was: 130,000 for brush border type, and 160,000 for lymph type. Fat administration significantly increased the ALP activity in intestinal lumen and intestinal lymph. However, it did not change biological characteristics of ALP including binding ability to lectins and electrophoretic mobility in any of these four fractions. These results suggest that lymphatic ALP may be transported from cytosol of intestinal cells and that fat administration seems to induce quantitative change of intestinal ALP, but not to change its physiological route of transportation into intestinal lymph. PMID- 2311254 TI - Enzymatic heterogeneity of seminomas. AB - Heterogeneity of placental-like alkaline phosphatase (PLAP-like enzyme) in seminoma was studied. PLAP-like enzyme from seminoma tissues was separated into three areas with different proportions between tumors, while PLAP and PLAP-like enzymes in normal testes were separated into two areas on the basis of hydrophobicity. By use of lectin affinity chromatography, PLAP-like enzyme in seminoma revealed extra sugar chains compared to PLAP, indicating heterogeneity of the carbohydrate moiety. However, the glycosylation patterns were found to be essentially similar between seminoma and normal testis. On isoelectric focusing, differences in migration patterns of PLAP-like enzyme were revealed between seminoma and normal testis as well as between PLAP-like enzyme and PLAP. The differences in charge were mainly due to differences in sialylation of the molecules. The complex pattern on isoelectric focusing was not altered by neuraminidase treatment, indicating a considerable charge heterogeneity within the population of PLAP-like enzyme molecules from seminoma. PMID- 2311255 TI - Purification and partial characterization of the placental-like alkaline phosphatase in human lung tissue. PMID- 2311256 TI - Placental-type alkaline phosphatase in peritoneal fluid of women with endometriosis. AB - Alkaline phosphatase (ALP) activities were studied in peritoneal fluid obtained from patients with untreated endometriosis and control women who had normal pelves. The patients (n = 18) had significantly higher total ALP (8.65 +/- 5.69 mU/mg, p less than 0.01) and thermostable ALP (0.28 +/- 0.23 mU/mg, p less than 0.05) than the controls (n = 7) (total ALP = 2.41 +/- 1.15; thermostable ALP = 0.09 +/- 0.04 mU/mg). The contents of the thermostable ALP in the total ALP were 4.5 +/- 2.4% for controls and 3.6 +/- 2.3% for patients. To define the biochemical characteristics of the thermostable ALP, the enzyme was partially purified from a mixture of peritoneal fluid from 16 patients. The partially purified, heated ALP (PFALP) responded to the various inhibitors, activators, and pH values tested in a significantly similar manner as a purified, heated human placental ALP did. Our data suggest that PFALP may be a placental-type (or Regan) ALP. PMID- 2311257 TI - Placental-like alkaline phosphatase from ovary and ascites of a patient with a malignant ovarian tumour. PMID- 2311258 TI - An alkaline phosphatase reacting with both monoclonal antibodies to intestinal and placental isoenzymes. PMID- 2311259 TI - Experimental studies on unconjugated bilirubin binding by human erythrocytes. AB - The evaluation of the bilirubin bound to human erythrocytes is considered by some paediatricians as a test to estimate the risk of development of kernicterus. We have studied the physical and chemical characteristics of this binding. Red blood cell membranes contain specific binding sites for bilirubin, the affinity of which is low (Kd = 170 mumol/L). The dissociation constant of the bilirubin/human serum albumin complex is about 10,000 times lower. In jaundiced neonates even with a level of blood bilirubin higher than 300 mumol/l, the binding of bilirubin to red blood cells is negligible. So, the evaluation of the bilirubin bound to human red blood cells does not seem to be a useful test to appreciate the risk of development of kernicterus. PMID- 2311260 TI - Serial measurements of Ca antigen in sera from patients with advanced malignant breast disease. AB - Ca antigen levels in serum samples from three groups of patients were assayed. From a survey of 173 patients with various malignancies, elevated levels were found most consistently in patients with metastatic breast cancer. Spearman rank correlation values of Ca and CEA values on individual serum samples, 0.3009, (n = 194), or individual and serial samples, 0.2406, (n = 264) from a total 194 patients with metastatic breast cancer showed that correlation between Ca and CEA values was poor. For a group of 20 patients within the 194, from whom fortnightly serial samples were available, serum levels for 10/20, measured retrospectively, corroborated clinical observations on the course of their disease, although only 4/20 showed marked elevations during active disease. No correlations between expression of the tumour marker and histological type of the primary tumour, age of the patient, site of recurrence nor aberrant elevation in response to cytotoxic drug could be found to explain the non-correspondence of marker behaviour and disease status in the remaining 10 patients. The indications from this small study are that serial Ca antigen serum measurement could be misleading in 50% of patients with metastatic breast cancer, and that the assay is unsuitable for follow-up of patients with breast cancer. PMID- 2311261 TI - Human liver nicotinamide N-methyltransferase: ion-pairing radiochemical assay, biochemical properties and individual variation. AB - Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide, pyridine, and structurally related compounds. The products of this reaction are positively charged pyridinium ions that cannot be removed from aqueous solution by simple organic solvent extraction. We developed an assay for human liver NNMT based on the extraction of the positively charged reaction product into 60% isoamyl alcohol in toluene in the presence of the ion-pairing reagent 1-heptanesulfonic acid. Nicotinamide was the methyl acceptor for the reaction, and [14C-methyl]-S-adenosyl-L-methionine (Ado-Met) served as the methyl donor. Apparent Km values of human liver NNMT for nicotinamide and Ado-Met were 347 and 1.76 mumol/l, respectively. The product of the reaction was identified as N1-methylnicotinamide (NMN) by high performance liquid chromatography. NNMT activity was inhibited by the reaction products, NMN and S-adenosyl-L homocysteine. NNMT activity was not affected by inhibitors of other methyltransferases including Ca2+, SKF 525A and 3,4-dimethoxy-5-hydroxybenzoic acid. Individual variation in NNMT activity was studied by measuring hepatic enzyme activities in 163 human liver biopsy samples obtained during clinically indicated surgery. The average NNMT activity in these samples was 51.5 +/- 32.5 U per mg protein (mean +/- SD), and there was not a significant correlation of enzyme activity with patient age or with the time of storage of the biopsy samples at -80 degrees C. The distribution of activities was bimodal, and approximately 26% of the samples were included in a subgroup with high NNMT activity. It will now be possible to test the hypothesis that individual differences in hepatic NNMT activity might be related to variation in the N methylation of pyridine compounds and to individual differences in either toxicity or the therapeutic efficacy of such compounds. PMID- 2311262 TI - Quantitation of hydrogen peroxide formed during UV-visible irradiation of protoporphyrin, coproporphyrin and uroporphyrin. AB - Free porphyrins are strong photosensitizers. Previously reported findings indicate that the in vitro cell lysis induced by irradiation in the presence of coproporphyrin (CP) and uroporphyrin (UP) is mediated by H2O2 and that induced by irradiation with protoporphyrin (PP) is not mediated by H2O2. In the present study the possible role of H2O2 in the porphyrin photosensitization was investigated by direct measurement of the H2O2 formed during the irradiation of PP, CP and UP. Our results show that the amount of H2O2 formed decreased in the following order: UP, CP, PP. The amounts of H2O2 formed during irradiation of CP and PP were approximately 86% and 38% respectively in comparison to the H2O2 formed during the irradiation of UP. The formation of H2O2 was inhibited by sodium azide, a strong quencher of singlet oxygen. These observations are in good agreement with the previous report that the in vitro photolysis of Ehrlich ascites carcinoma cells by UP and CP, but not that by PP, was inhibited by catalase and clinical findings with patients with erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT). The patients with EPP, where the photosensitivity is due to PP, respond well to beta-carotene while beta-carotene does not protect against the photosensitivity in PCT, in which case the photosensitivity is due to uroporphyrin. PMID- 2311263 TI - Quantitative assay of free and total carnitine using tandem mass spectrometry. AB - A new, specific method for isotope dilution assay of total and free carnitine in urine has been developed. The method utilizes fast atom bombardment ionization with tandem mass spectrometry and requires minimal sample preparation. It compared well with radioenzymatic assay in terms of specificity, precision and accuracy, but was much more convenient in terms of analysis time and sample throughput. The new method is also applicable to the determination of free and short-chain total carnitine in plasma. PMID- 2311264 TI - Low biotinidase activities in the sera of patients with impaired liver function: evidence that the liver is the source of serum biotinidase. PMID- 2311265 TI - Defective oxidation of pristanic acid by fibroblasts from patients with disorders in propionic acid metabolism. AB - The alpha-methyl fatty acid, pristanic acid (2, 6, 10, 14 tetramethylpentadecanoic acid) is oxidised rapidly by normal skin fibroblasts in culture to CO2 and to water-soluble metabolites. The latter are secreted into the culture medium. Fibroblasts from patients with propionyl CoA carboxylase, and to a lesser extent from patients with methylmalonyl CoA mutase defects, show reductions in the amount of CO2 released, although the production of water soluble metabolites is not affected. Our data indicate that propionic acid is produced from pristanic acid, and ultimately from its immediate precursor phytanic acid. As phytanic and pristanic acids are significant components of diets rich in ruminant fats, it is likely that they may contribute to the accumulation of propionate and its metabolites in disorders of propionate metabolism. PMID- 2311266 TI - 5p;12q translocation with manifestations of cri du chat syndrome and Marfanoid arachnodactyly. AB - A 12-year-old boy with a history of a mewing cry after birth, severe mental retardation, Marfanoid arachnodactyly, general osteomalacia and multiple bone fractures was found to have a de novo 5p;12q chromosomal translocation. The karyotype is 46,XY,t(5;12)(12qter----12q24.1::5p15----cen----5qt er; 12pter--- cen----12q24.1). The karyotypes of other examined family members are normal. The manifestations of cri du chat syndrome are explained by the loss of a small segment of 5p15 which is responsible for the major stigmata of the syndrome, and the abnormalities of the osseous system may be the results of untreated vitamin D resistant rickets. PMID- 2311267 TI - Complex familial translocation. PMID- 2311268 TI - On the familial occurrence of congenital bilateral absence of vas deferens. PMID- 2311269 TI - Somatic and germ-line mosaicism in autosomal dominant antecubital pterygium. PMID- 2311271 TI - Reticulohistiocytoma cutis--review of 15 cases and an association with systemic vasculitis in two cases. AB - We reviewed 15 cases of reticulohistiocytoma cutis (RHC). Three cases were of solitary lesions. Four cases were associated with a destructive arthritis but no other systemic features. One additional patient had a destructive arthritis and lesions of reticulohistiocytoma in synovium, larynx, and mucosa. Three patients had associated xanthelasma. Two cases were associated with internal malignancy (metastatic malignant melanoma, adenocarcinoma of the bowel). Two cases were sequentially associated with systemic vasculitis (Wegener's granulomatosis, periarteritis nodosa). This occurrence of systemic vasculitis in RHC patients is unique. RHC may have variable cutaneous and systemic manifestations and associations with malignancy and immunoinflammatory diseases, including vasculitis. PMID- 2311270 TI - A dicentric variant of chromosome 6: characterization by use of in situ hybridisation with the biotinylated probe p308. AB - An unusual variant of chromosome 6 was shown to be a dic(6) by use of the chromosome specific alphoid probe, p308. The use of biotinylated repeat probes provides a rapid procedure for the resolution of some cytogenetic abnormalities. PMID- 2311272 TI - Cholesterol sulphate levels in the hair and nails of patients with recessive X linked ichthyosis. AB - Cholesterol sulphate (CS) has been suggested as an intercellular glue for corneocyte-corneocyte cohesion from studies on patients with recessive X-linked ichthyosis (RXLI). Pathological stratum corneum of RXLI patients was found to show a significant elevation of CS. In the present study hair and nails, unaffected keratinized tissues in RXLI patients, were examined for CS levels. The results demonstrated significantly elevated CS levels in both tissues in RXLI patients (P less than 0.001). In particular the mean CS level in the hair of RXLI patients was five times greater than normal. The present study suggests that hair is a useful material for the diagnosis of RXLI. PMID- 2311273 TI - Complement activation in psoriasis. AB - Plasma from 16 patients with psoriasis and 12 healthy control subjects were measured for iC3b, C4d, and Bb fragments generated by complement activation. Plasma concentrations for iC3b, C4d, and Bb fragments were found to be significantly increased in the patients with psoriasis. The highest concentrations of these complement activation fragments were seen in patients with erythrodermic pustular psoriasis, psoriatic arthritis, and Reiter's syndrome. The serum concentrations of complement components and regulatory proteins were normal or elevated in almost all samples. PMID- 2311274 TI - Two tuberculides in one patient--a case report of papulonecrotic tuberculide and erythema induratum occurring together. AB - A patient is described in whom erythema induratum and papulonecrotic tuberculide occurred simultaneously. Clinical and histological appearances were characteristic as was the response to antituberculous chemotherapy. PMID- 2311276 TI - Individual and instrumental variations in irritant patch-test reactions--clinical evaluation and quantification by bioengineering methods. AB - A major purpose of irritant patch testing is to differentiate between normal, delicate and less sensitive skin. To assess the usefulness of irritant patch testing, knowledge of variation in responses to identical patch tests is essential. In the present study inter- and intra-individual variation in irritant patch test reactions due to sodium lauryl sulphate and nonanoic acid is given when evaluated by traditional visual scoring as well as different non-invasive methods, i.e. measurement of transepidermal water loss, the hydration state of stratum corneum by electrical conductance, cutaneous blood flow by laser Doppler flowmetry, and measurement of skin thickness by 20-MHz ultrasound A-scan. The intra-individual 'site-to-site' variation was considerably less than the inter individual variation, which is essential to differentiate between persons with delicate and less sensitive skin. Methods used were relevant for this purpose except for the measurement of electrical conductance. PMID- 2311275 TI - Amino-acid composition in trichorrhexis nodosa. AB - Trichorrhexis nodosa is a common shaft defect affecting scalp hair. Two-hundred scalp hairs exhibiting trichorrhexis nodosa were obtained from two normal females; samples were prepared from proximal shaft, pre-nodule, nodule and post nodule sections and analysed for their respective amino-acid compositions. Significant reductions in cystine (P less than 0.001) of the pre-nodule, nodule and post-nodule sections, which decreased by 17.2%, 19.8% and 14.3%, respectively, and an increase in the acidic amino acids (P less than 0.03) were found, compared to values obtained from proximal shaft of the same hairs. The majority of nodules occurred within the last 10% of the shaft, and the similarity in amino-acid compositions between pre-nodule, nodule and post-nodule sections suggests that 'weathering' is the major factor influencing nodule occurrence. It is postulated that nodule formation requires a specific degree of exposure to 'weathering' together with a reduction in cuticle cell coverage. It is suggested that an initial structural defect, created by a change in the DNA coding for a cuticle polypeptide fraction, could be responsible for the selective and isolated presentation of the nodule within a 'weathered' section of hair shaft. PMID- 2311277 TI - Natural history of androgenetic alopecia. AB - Twenty-two men with patterns III-Va androgenetic alopecia were entered into a 10 month study aimed at establishing information on the natural progression of hair loss over a period of time typical of studies of hair growth promoters. The methodology employed was the same as that in published clinical trials of topical minoxidil, but the men refrained from application of either active drug or vehicle to their scalps. As one of the potential explanations for the observed 'placebo-effect' seen in non-vellus hair counts in the topical minoxidil trials was a learning curve of novice hair counters, we were particularly interested in evaluating this in our 'no-treatment' trial. To that end, both a novice (Observer I) and an experienced (Observer II) hair counter independently performed the hair counts. There was a mean decline in the number of vertex target area non-vellus hairs (-17.2 +/- 80.3 for Observer I and -26.6 +/- 63.5 for Observer II) at the end of 10 months; this was not significant. The novice's hair counts were lower than the experienced observer's counts at baseline, and the difference remained relatively constant during the study. Without the application of a placebo, there was no increase in hair growth, making it unlikely that the methods of hair counting led to the 'placebo-effect' seen in prior topical minoxidil studies. PMID- 2311278 TI - Cutaneous granulomata complicating desensitization. AB - D-VAC Pollens (Bencard), a standard depot pollen vaccine, was withdrawn in the mid-1970s. We report a case in which subcutaneous granulomata developed 12 years after desensitizing injections by this product. PMID- 2311279 TI - Hypothesis--the natural selection of psoriasis. AB - The high genetic frequency of some inherited disorders may in part be related to a survival advantage conferred against an environmental hazard. Psoriasis is an inherited disorder which is common amongst populations of northern latitudes. Cutaneous delayed-type hypersensitivity response to streptococcal antigen is altered in such patients with a decrease in induration and erythema. Scarlet fever has until recently been associated with a high childhood mortality, the pathogenesis of which is related to interdependent primary toxicity and secondary toxicity (including delayed-type hypersensitivity) to streptococcal antigen (erythrogenic toxin), leading to cellular damage and potentially lethal shock. Streptococcal infection, usually presenting as pharyngitis, is a classical trigger for both scarlet fever and psoriasis. Individual susceptibility to scarlet fever has been clinically assessed in the past by the Dick test--an intradermal injection of the filtrate of a broth culture of scarlatina-producing strains of Streptococcus giving an erythematous reaction at 24-48 h (Dick positive). The degree of reaction is directly related to susceptibility to scarlet fever. The severity of and mortality from scarlet fever may be ameliorated by immunological mechanisms also found in psoriatic patients. The high prevalence of psoriasis amongst some populations today may be related to such a protective factor. PMID- 2311280 TI - Dysplastic naevi in association with partial deletion of chromosome 11. AB - A patient is reported who developed dysplastic naevi at an early age. He also suffered from a syndrome including Wilms' tumour, aniridia, mental retardation and diabetes mellitus in association with an interstitial deletion of the short arm of chromosome 11. It is suggested that genetic factors may be important in sporadic as well as familial cases of the dysplastic naevus syndrome. PMID- 2311281 TI - Cutaneous lymphangiectases after therapy for carcinoma of the cervix--a case with unusual clinical and histological features. AB - Secondary lymphangioma (lymphangiectasis) has been reported as a consequence of lymphatic damage. No specific histological criteria can be used to differentiate primary lymphangioma circumscriptum from lymphangiectasis. We describe a woman who developed lymphangiectases on both non-lymphoedematous upper thighs after hysterectomy and radiation therapy for carcinoma of the cervix. This case differs from the secondary lymphangiomas reported previously in that the vascular channels appeared in newly formed adventitial dermis without histological changes in the epidermis. PMID- 2311282 TI - Cutaneous presentation of sarcoidosis in an infant. AB - A 4-month-old infant developed a symptomless erythematous maculopapular rash on her abdomen spreading to involve other areas of her trunk and limbs. Skin biopsy showed the features of sarcoidosis and she later developed sarcoid uveitis and arthritis requiring systemic steroid therapy. PMID- 2311283 TI - Multiple angiolipomata treated with intravenous infusions of lignocaine. AB - A 54-year-old woman with multiple tender angiolipomata was treated with intravenous infusions of lignocaine (5 mg/kg) in saline in a double-blind trial. The pain disappeared but reappeared gradually 3 weeks later. Central mechanisms may explain the mode of action of lignocaine. Infusions should be carried out during cardiac monitoring. PMID- 2311284 TI - Angiolymphoid hyperplasia with eosinophilia limited to the vulva. AB - A patient with angiolymphoid hyperplasia with eosinophilia is described. This is, to our knowledge, the first case report in which the lesions were located on the vulva. PMID- 2311285 TI - Exacerbation of psoriasis precipitated by an oestradiol-testosterone implant. AB - A 47-year-old woman developed widespread psoriasis following insertion of a combined oestradiol-testosterone implant into her anterior abdominal wall for post-oophorectomy symptoms. The rash did not resolve until the effects of the implant had worn off and recurred following insertion of a second oestradiol testosterone implant. Implants containing oestradiol alone were tolerated. We have found no previous reports suggesting a relationship between testosterone implants and psoriasis. PMID- 2311286 TI - Langerhans cells and mycosis fungoides--a critical overview of their pathogenic role in the disease. AB - Skin biopsies from seven patients with mycosis fungoides in various clinical stages (patches, plaques, nodules) were studied immunohistochemically and ultrastructurally, with the aim of investigating and quantifying the distribution of Langerhans cells and their relationships to mycosis cells. Our findings have revealed that in patches and plaques both Langerhans cells and mycosis cells were numerous in the epidermis. Notwithstanding this, in all the specimens examined, only one Langerhans cell forming close contact with a mycosis cell was detected. In the nodules, Langerhans cells and mycosis cells were sparse in the epidermis and no contacts were seen between them. Moreover, in all the patients studied, only a single Langerhans cell was found in the dermal infiltrate without any closely related mycosis cells. Conversely, numerous interdigitating cells have been found in the dermis of patches and plaques, often tightly adhering to mycosis cells. In the nodule, a few scattered interdigitating cells were seen, but often these had close contacts with neoplastic lymphoid cells. These findings indicate that close apposition between Langerhans cells and mycosis cells, which led previous authors to hypothesize a persistent stimulatory action of Langerhans cells on T lymphocytes, eventually leading to the malignant transformation of the latter, is unusual in mycosis fungoides. Therefore, if such a pathogenic role may be attributed to accessory cells in mycosis fungoides it is more probably exerted by dermal interdigitating cells and not by Langerhans cells, as previously proposed. PMID- 2311287 TI - Generalized granuloma annulare in a patient with temporal arteritis--are these conditions associated? AB - A case of generalized granuloma annulare associated with temporal arteritis is described. The patient, a 79-year-old man, noticed numerous asymptomatic lesions on his trunk and extremities for 3 months. Four months later, he suffered from headache and loss of vision. Both were successfully treated by oral administration of prednisolone. PMID- 2311288 TI - Patch testing against Pityrosporum antigen. PMID- 2311289 TI - Oral 8-methoxypsoralen as a cause of topical phototoxicity. PMID- 2311290 TI - High cumulative dose of ultraviolet radiation is a contraindication for cyclosporin therapy. PMID- 2311291 TI - The effect of dithranol treatment on vitiliginous skin. PMID- 2311292 TI - Acropustulosis of infancy in a twin. PMID- 2311293 TI - Drugs and side-effects. PMID- 2311294 TI - The level of mannan-binding protein regulates the binding of complement-derived opsonins to mannan and zymosan at low serum concentrations. AB - When sera diluted to 5% in a buffer containing calcium and magnesium were incubated with mannan-coated ELISA plates, C4 fragments, properdin and factor B were bound to the plates as well as the expected opsonic C3 fragments, C3b and C3bi. The calcium-dependent lectin mannan-binding protein, which is structurally similar to C1q, was also shown to bind in this assay and analysis of sera from 179 healthy blood donors revealed that the binding levels of all these proteins were highly significantly correlated. Results obtained with a previously described C3b opsonic assay using zymosan also correlated with the mannan-binding levels. When the sera were diluted to 5% in the presence of Mg-EGTA there was no detectable binding of complement proteins to the mannan surface, confirming that no alternative pathway activation occurred at this serum concentration. When sera were diluted to 5% in a buffer containing EDTA in order to study immunoglobulin binding in the absence of complement activation, the levels of bound IgG1, IgG2, IgG3, IgA and IgM antibodies were found to be completely unrelated to the C3bi binding levels previously observed. The results suggest that in this experimental system using low concentrations of serum, mannan-binding protein initiates an antibody-independent mechanism of cleavage of the classical pathway component C4, which subsequently regulates the degree of cleavage of C3 and recruitment of alternative pathway proteins. PMID- 2311295 TI - Complement activation and the prognostic value of C3a in patients at risk of adult respiratory distress syndrome. AB - In vivo and in vitro studies have shown that complement activation plays an important role in the pathogenesis of the adult respiratory distress syndrome (ARDS). In a prospective study of polytrauma patients at risk of ARDS (n = 38) complement parameters were determined over a period of 14 days in serial plasma samples (obtained every 6 h during the first 48 h). Polytrauma induced a rapid and remarkable complement activation. Low levels of the complement proteins C3, C4, C1 inhibitor (C1 INH) factor I and factor H during the first 48 h indicated complement consumption in all patients. Elevated C3a levels in the first few hours after injury were associated with the later development of ARDS. A more sensitive indicator than C3a alone was the calculated C3a:C3 ratio discriminating ARDS and non-ARDS patients. A second rise of C3a levels and C3a:C3 ratio from day 4 on paralleled the course of extravascular lung water. To assess the mode of complement activation, the activation-specific protein complexes C1rC1s-C1 INH and C3b(Bb)P were measured in some of the patients. We demonstrate that in the first 48 h complement activation occurred via the alternative pathway only and was later followed by an additional activation via the classical pathway. Our observations suggest that monitoring of C3a and C3 in plasma can identify polytrauma patients at high risk for ARDS at an early stage of the disease. PMID- 2311296 TI - Hashimoto's thyroiditis manifesting monoclonal lymphocytic infiltration. AB - Hashimoto's thyroiditis (HT) and lymphoma are sometimes difficult to distinguish between. Moreover, lymphoma sometimes develops in a thyroid gland from pre existing HT. Open- or large-needle biopsy usually distinguishes between them; the specimen may be examined histologically and subjected to immunohistochemistry. Another possible method of examination is fine-needle aspiration biopsy (FNAB). The cells obtained may be evaluated cytologically, and subjected to flow cytometry, using various antibodies. In this study, anti-kappa and anti-lambda antibodies are especially important, as a gross predominance of kappa or lambda B lymphocytes infiltrating the thyroid is evidence for a B cell monoclone. In this study, 15 patients were selected because of their rapidly growing goitres. They all underwent FNAB. Five had cytology typical of HT, and no evidence of monoclonality on flow cytometry. They were diagnosed as HT without further histopathology. The remaining 10 patients had cytology suspected of lymphoma, or evidence of monoclonality on flow cytometry, or both. These patients underwent open- or large-needle biopsy. Only three of them were diagnosed histopathologically as lymphoma; the other seven were diagnosed histopathologically as HT, making 12 cases of HT in all. Five of these 12 cases, and one of the three cases of lymphoma showed flow cytometrical evidence of monoclonality; thus evidence of monoclonality from FNAB, while interesting, does not necessarily serve to differentiate between HT and lymphoma. Furthermore, the immunohistochemical assessment of monoclonality did not correlate with the flow cytometrical assessment. Follow-up evidence will be required to discover whether those patients with a B cell monoclone in their HT are the ones who develop a lymphoma. PMID- 2311297 TI - Thyroid peroxidase and the induction of autoimmune thyroid disease. AB - Animal models of autoimmune thyroid disease are associated with thyroglobulin (Tg) as autoantigen whereas in man the autoimmune response to microsomal antigen/thyroid peroxidase (TPO) appears to play a major role in thyroiditis. Consequently, we have compared the ability of TPO and Tg to induce thyroid autoantibodies and thyroid damage in mice known to be susceptible (CBA/J) or resistant (BALB/c) to thyroiditis induced using murine Tg. Groups of three to five mice were immunized twice using Freund's complete adjuvant with 80-100 micrograms highly purified porcine (p) TPO, pTg, rat (r) Tg, human Tg, bovine serum albumin (BSA) or BSA + 0.2 micrograms pTg (the level of Tg contamination of TPO). Four weeks after immunization with TPO, plasma from CBA/J (but not BALB/c) mice contained IgG class antibodies which bound to TPO-coated tubes in the presence or absence of excess Tg (and could therefore be clearly distinguished from Tg antibodies) but there was no evidence of thyroiditis in either strain of mice. In contrast, in CBA/J mice immunized with rTg and, to a lesser extent in mice that had received pTg, thyroid tissue was infiltrated with lymphoid cells and/or neutrophils and antibodies to pTg (but not pTPO) were present. Our observations demonstrate that induction of TPO antibody alone is insufficient to lead to thyroiditis in CBA/J mice. Further, these studies emphasize the complex interactions between MHC and different thyroid antigens in the processes leading to thyroid destruction. PMID- 2311298 TI - Synovial fluid antigen-presenting cells unmask peripheral blood T cell responses to bacterial antigens in inflammatory arthritis. AB - We and others have previously shown that synovial fluid (SF) mononuclear cells (MC) from patients with both reactive arthritis and other inflammatory arthritides proliferate in vitro in response to bacteria clinically associated with the triggering of reactive arthritis. In all cases, such SFMC responses are greater than the corresponding peripheral blood (PB) MC responses, often markedly so, and the mechanism for this is unclear. We have investigated this phenomenon by comparing the relative abilities of irradiated non-T cells derived from PB and SF to support autologous T cell responses to ReA-associated bacteria. Seven patients whose SFMC had been shown previously to respond to bacteria were studied. We demonstrate antigen-specific responses of PB T cells to bacteria in the presence of SF non-T cells which are in marked contrast to the minimal responses of either unfractionated PBMC or PB T cells reconstituted with PB non-T cells. We also show that PB, but not SF T cells respond strongly to autologous SF non-T cells in the absence of antigen or mitogen. These findings demonstrate that SF antigen-presenting cells (APC) are potent activators of PB T cells. We conclude that the contrasting responses of SFMC and PBMC to bacterial antigens may be accounted for at least in part by an enhanced ability of SF APC to support T cell proliferative responses. PMID- 2311299 TI - Quantitative study of Leishmania braziliensis braziliensis reactive T cells in peripheral blood and in the lesions of patients with American mucocutaneous leishmaniasis. AB - A limiting dilution analysis (LDA) was utilized to estimate the frequency of L. braziliensis braziliensis reactive T cells (Lbb-T cells) in peripheral blood and in the lesions of patients with mild localized cutaneous leishmaniasis (LCL) or with severe mucosal leishmaniasis (MCL). The frequencies of Lbb-T cells in peripheral blood varied from 1:107300 to 1:3587 and were not significantly different in MCL and LCL patients. However, a significant difference was encountered (P less than 0.02) between the T cells frequencies in cutaneous (1:748 to 1:45) and mucosal lesions (1:152 to 1:13). A positive correlation was also observed between these frequencies and the magnitude of delayed-type hypersensitivity (DTH) (P less than 0.01) and the presence of fibrinoid necrosis and granulomatous reaction in the site of the lesions (P less than 0.05). The lack of correlation between the severity of disease (MCL or LCL) and the frequency of Lbb-T cells in peripheral blood gave no indications towards understanding the physiopathology of severe or mild disease. However, the correlation between high T cell frequencies in the site of the lesions, the magnitude of DTH, the fibrinoid necrosis and the severity of the disease (MCL lesions) points to the possibility that the presence of a strong T cell dependent cellular immune response in the site of the lesions may have a deleterious effect. However, a local well modulated T cell immune response might provide healing of the lesions. PMID- 2311300 TI - Mechanism of a lymphocyte abnormality associated with HLA-B8/DR3: role of interleukin-1. AB - Lymphocytes from normal individuals with the histocompatibility antigens HLA-B8 and DR3 have impaired proliferative responses when stimulated with suboptimal concentrations of mitogens. We have previously shown that an important factor in the impaired response is a failure to produce normal quantities of interleukin-2 (IL-2). To examine the mechanism of decreased responsiveness further, we measured interleukin-1 (IL-1) production of low responder subjects compared with controls. The peripheral blood mononuclear cells of five low responder individuals with HLA B8/DR3 stimulated with 0.05 micrograms/ml of phytohaemagglutinin (PHA) accumulated only 0.036 U/ml of IL-1 compared with 0.32 U/ml for normal responders. There was a highly significant correlation between the PHA-stimulated IL-1 concentration at 12 h and the subsequent IL-2 concentration at 48 h(r = 0.89, P less than 0.0001) suggesting a role of decreased IL-1 production in the impaired response. A study of unfractionated or column-fractionated culture supernatants revealed no evidence that the decreased IL-1 activity in the supernatants of low responder subjects was related to increased IL-1 inhibitor concentrations. These results suggest that impaired IL-2 production and lymphocyte proliferation in healthy subjects with HLA-B8/DR3 may be mediated at least in part by decreased IL-1 production, and implicates a defect of a very early event in lymphocyte activation. PMID- 2311301 TI - Lymphoid and non-lymphoid cells in the adenoid of children with otitis media with effusion: a comparative study. AB - We characterized on immuno- and enzymecytochemical level the lymphoid and non lymphoid cells in the adenoid of children with upper respiratory tract infections (URI) and otitis media with effusion (OME) and compared these with the adenoid of children with URI without OME and with the adenoid of 'healthy' children and adults. Besides macrophages and dendritic cells we also showed the presence of MHC class II positive, ciliated, epithelial cells. These non-lymphoid cells were present in all adenoids. However, their number was less than 1% of all cells. We found no difference in lymphocyte subsets from children with URI + OME compared with those from children with URI alone. These two groups showed a significant decrease of CD8-positive (suppressor/cytotoxic) cells and a slight increase in CD22-positive B cells in comparison to 'healthy' children. No difference was found in percentages of CD4-positive (helper/inducer) cells. The localization of the lymphoid subsets in adenoids of children with URI and/or OME did not differ from those of 'healthy' children and adults. PMID- 2311302 TI - Repeated exposure to bacterial lipopolysaccharide interferes with disposal of pathogenic immune complexes in mice. AB - Patients with systemic lupus erythematosus (SLE) experience clinical flares in association with superimposed bacterial infection. To investigate whether heightened immune phenomena during the course of bacterial infections were related to abnormal disposal of immune complexes, we administered bacterial lipopolysaccharide (LPS) to C57BL/6 mice for 5 weeks. Control mice received vehicle only. We then challenged the mice with a subsaturating dose of radiolabelled immune complexes intravenously and determined the localization of immune complexes in liver, spleen and kidney. In comparison to control mice, mice exposed to LPS developed features of polyclonal B cell activation, autoimmune phenomena, delayed removal of immune complexes from the circulation, diminished liver uptake of immune complexes, and enhanced localization of immune complexes in the kidneys. The findings could not be attributed to biological processes dependent on complement concentration. Instead, interferences with Fc receptor function, or with endocytosis of immune complexes may represent likely possibilities. Thus, clinical flares in patients with SLE, in the presence of a superimposed infection, may result from enhanced localization of immune complexes in organs due to altered mechanisms of their disposal. PMID- 2311303 TI - Prostaglandin E1 suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage-dependent glomerulonephritis. AB - Prostaglandin E1 (PGE1) suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage dependent glomerulonephritis. Macrophages are mediators of glomerular injury in models of proliferative glomerulonephritis. We have recently shown that macrophages in glomerulonephritis have low prostaglandin E2 (PGE) generation, and other evidence implicates eicosanoids as regulators of macrophage activation. Here we have studied in rats the effect of 15(s)-15-methyl PGE1 (M-PGE1) on accelerated nephrotoxic nephritis, a model of acute macrophage-dependent glomerular injury. M-PGE1 ameliorated proteinuria (day 4; 61 +/- 13 mg/24 h, n = 9; vehicle treated, 164 +/- 17 mg/24 h, n = 11; P less than 0.002) and glomerular hypercellularity; quantification of infiltrating macrophages by isolating glomerular cells showed reduction in the numbers of macrophages (44 +/- 9/glomerulus; vehicle treated, 119 +/- 15/glomerulus; P less than 0.02) with inhibition of Ia antigen expression on infiltrating macrophages (8 +/- 5%; vehicle treated 25 +/- 4% P less than 0.05). Glomerular binding of nephrotoxic globulin and levels of autologous antibodies were not affected by M PGE1. Thus the mechanism of suppression involves inhibition of macrophage accumulation and activation. M-PGE1 administered to normal rats did not affect numbers of resident leucocytes (12.6 +/- 1.5/glomerulus; vehicle treated, 13.2 +/ 1.3/glomerulus) or alter Ia antigen expression (4.1 +/- 0.2 Ia + cells/glomerulus; vehicle treated, 3.9 +/- 0.6/glomerulus). This study suggests a therapeutic role for PGE1 in this type of glomerulonephritis, and has implications for the pathophysiology of macrophage-mediated inflammation. PMID- 2311304 TI - The effect of cyclosporin A on the interstitial mononuclear cell infiltration and the induction of Heymann's nephritis. AB - Heymann's nephritis was induced with brush-border (BB) antigen. Interstitial mononuclear cell infiltration was studied with cytological examinations of fine needle aspiration biopsies (FNAB), and with immunoperoxidase stains of frozen sections with monoclonal antisera. The effect of cyclosporin A (CyA), 20 mg/kg when administered intraperitoneally for 8 days in association with both initial immunization, and with the booster 4 weeks later, on the interstitial leukocyte infiltration and on the development of membranous glomerulonephritis (MGN) and proteinuria were investigated. Another group of rats was immunized, but not given CyA. Experimental animals were killed in groups 3, 6 and 20 weeks after initial immunization. CyA inhibited significantly the initial interstitial lymphocyte and blast cell response at 3 weeks (FNAB), but did not inhibit the secondary response after the booster. The anti-BB titre reacted in a similar fashion. Immunoperoxidase stains indicated a clearly suppressed T suppressor/cytolytic (T s/c) cell response. Glomerular basement membrane (GBM) deposits of IgG developed more slowly and were more scarce in the CyA-treated rats, when compared with the untreated group. Only one out of 15 CyA treated rats developed C3 deposits in the GBM during the course of the study, and none developed proteinuria, when most untreated rats (10/17) had C3 deposits and were nephrotic at 20 weeks. Thus, CyA depressed the initial interstitial cellular response after immunization with BB antigen, and also inhibited the development of antibody response, C3 deposits and proteinuria of Heymann nephritis. These effects of CyA may be contributed to an inhibited amplification of the autoimmune response associated with interstitial damage and continuous release of autoantigen. PMID- 2311305 TI - Role of antigen-presenting cells in variation in immunogenicity of mycobacteria. AB - The route of immunization was observed to play a significant role in deciding the outcome of immunization with killed mycobacterial vaccines. Whereas the slow growers were immunogenic by both intraperitoneal and intradermal routes, the rapid growers were immunogenic only by intradermal route. The non-responder state of mice to Mycobacterium vaccae by i.p. route of immunization could be corrected by prior treatment with poly I:poly C, an interferon inducer, or indomethacin, a prostaglandin inhibitor. Antigen-presenting efficiency of peritoneal and spleen cells were compared employing M. vaccae and M. tuberculosis H37Rv primed T cells and corresponding sonicates as antigens in an in vitro lymphocyte transformation test. Irradiated spleen cells presented both the antigens efficiently. However, with peritoneal cells as antigen-presenting cells, proliferative response against only M. tuberculosis was observed; proliferation of M. vaccae primed T cells was very poor. Peritoneal cells of poly I:poly C treated mice showed distinct improvement in their efficiency of presentation; even paraformaldehyde-fixed peritoneal cells gave an efficient stimulation with M. vaccae. The percentage of Ia-positive fraction in peritoneal cells was very low (5.95%) in comparison with spleen cells (38.37%). Poly I:poly C treatment resulted in increase in the Ia positive cell fraction of the peritoneal cells to 24.5%. PMID- 2311306 TI - Flare-up reaction of streptococcal cell wall induced arthritis in Lewis and F344 rats: the role of T lymphocytes. AB - One i.p. injection of a sterile suspension of streptococcal cell walls (SCW) induces chronic erosive polyarthritis in susceptible Lewis rats, but not in resistant F344 or nude Lewis rats. Because continuous exacerbations may be one possible mechanism underlying chronic disease, we studied the mechanism of these flare-up reactions in Lewis and F344 rats. Injection of SCW into the right knee joint of rats induced a transient monoarthritis in both strains. Reactivation of the subsided arthritis by i.v. administration of the same antigen could be evoked only in the Lewis rat. Even repeated i.v. challenges with SCW failed to induce a flare-up reaction in the F344 rat, while the Lewis rat went through an exacerbation after every challenge. Removal of T lymphocytes by monoclonal antibodies before induction of an exacerbation rendered Lewis rats refractory to flare-up reactions, thus indicating the T cell-dependence of this reaction. Furthermore, when cell walls from heterologous bacteria were tested for their capacity to induce exacerbations of SCW-induced monoarthritis and to induce proliferation of SCW-specific T lymphocytes in vitro, a strong correlation between both features was found, again pointing to a role for SCW-specific T cells in exacerbations. Together, these data support our hypothesis that chronic arthritis is the result from repeated reactivations of a waning arthritis which are dependent on antigen-specific T lymphocytes. PMID- 2311307 TI - IgA nephritis associated with plasminogen abnormalities. AB - Two patients with IgA nephritis associated with hereditary plasminogen abnormalities are described. One patient had dysplasminogenemia and the other had plasminogen deficiency. In both patients, renal biopsy specimens showed significant arteriosclerotic changes in addition to mesangial proliferation. Increased fibrinopeptide A concentration in their plasma suggested increased thrombin generation. In one patient, no systemic arteriosclerosis coexisted, judging from normal optic fundi and the absence of neurological and cardiac abnormalities. In IgA nephritis, renal vascular hyalinosis is often observed, probably resulting from vascular injury. Thus, it was suggested that the decreased fibrinolysis and renal vascular injury of these patients synergistically induced more fibrin thrombi and accelerated arteriosclerosis of the kidney. These cases imply the important role of fibrinolytic disorders in the progression of IgA nephritis. PMID- 2311308 TI - Effects of a gluten-free diet in primary IgA nephropathy. AB - In an uncontrolled study a gluten-free diet was given to 29 patients affected by primary IgA nephropathy (IgAGN). All of them followed the diet for 6 months, 23 patients for 1 year and 9 for 2 to 4 years. Mean levels of IgA containing circulating immune complexes (IgAIC), detected by a specific conglutinin assay and by measuring IgA content in 2.5% polyethylene glycol precipitates, on an unrestricted diet, significantly decreased after 6 months of gluten-free diet (p less than 0.01) and remained reduced during the follow-up. A decrease in IgAIC levels was evident in 85.7% of the cases with basal positive data, with complete normalization in 64.3% of them. IgA to gluten antigens (ethanol- or saline soluble gliadin, glutenin and the lectin fraction termed glyc-gli) as well as to heterologous bovine and egg albumins were found to be significantly increased on an unrestricted diet in the group of 14 IgAGN patients with basal positive IgAIC. The mean levels of IgA to most dietary antigens significantly decreased after 6 months to 1 year of a gluten-free diet. A decrease in IgA to ethanol-soluble gliadin was evident in 81.8% of the cases with basal positive data, with complete normalization in 63.6%. A subgroup of 27.5% of IgAGN patients showed positive IgAIC values associated with increased IgA values to a variety of dietary antigens. A gluten-free diet induced in 75% of the cases a parallel improvement in these abnormal immunological data. Mean proteinuria values were found to be significantly decreased after 6 months of the diet and a reduction was also observed in microscopic hematuria. However, mean blood creatinine levels showed a significant increase after the gluten-free diet. The data of this study indicate that a gluten-free diet can modify some immunological abnormalities in a group of IgAGN patients, reducing levels of IgAIC and IgA to dietary antigens. The clinical course does not seem to be favorably influenced, since a relentless progression towards renal failure was observed. PMID- 2311309 TI - Renal transplantation in 20 children with hemolytic-uremic syndrome. AB - In this study the outcome of kidney transplantation in 20 patients with end-stage renal disease (ESRD) due to the hemolytic uremic syndrome (HUS) was evaluated. The characteristics and severity of the primary disease in these patients were not different from those commonly reported in patients with HUS. Eleven children developed ESRD immediately following HUS, in nine others temporary partial recovery of kidney function for 0.5-13.2 years was observed. Twenty-four grafts were transplanted in these 20 patients. Graft survival was no different from overall cadaver graft survival. In nine patients failure of the first kidney graft occurred, while the four second grafts were still functioning at the time of writing. Recurrence of HUS was suspected but not proven to be the cause of first graft failure in two patients, and impaired graft function in a third one. A short interval between HUS and kidney transplantation seems to adversely affect graft survival. No other factors influencing outcome of transplantation could be detected. PMID- 2311310 TI - Renal function during calcitriol therapy in chronic renal failure. AB - Some authors have reported that vitamin D treatment worsens renal function. We studied 10 patients with stable renal function, who were given calcitriol (0.5 micrograms/day) for a 4-month period. Creatinine and inulin clearance were performed at the beginning and at the end of the treatment. Although serum creatinine increased and creatinine clearance decreased, inulin clearance did not show significant variations. Furthermore, serum creatinine fell to the baseline value within 60 days after discontinuation of vitamin D therapy. The increased serum creatinine may be explained by an augmented release from muscular tissue, probably due to the improvement of uremic myopathy induced by calcitriol. PMID- 2311311 TI - DNA analysis of cystic fibrosis genotypes in relatives with equivocal sweat test results. AB - Restriction fragment length polymorphism linkage analysis of cystic fibrosis (CF) is used primarily for pre-pregnancy family studies, prenatal diagnosis, and carrier testing among close relatives of an affected individual. We undertook to clarify the status of six individuals with borderline or elevated sweat chloride concentrations and a relative with CF by testing for haplotype sharing. Their families and physicians expressed concern about management of these generally asymptomatic individuals. We typed DNA from family members with pJ3.11, pXV2C, pKM19, pmetH, pmetD, and p7C22. Each family was fully informative, enabling us to track the CF region of chromosome 7. Our analysis identified five individuals from four families as CF heterozygotes. A sixth individual, whose maternal first cousin died from CF, has the same haplotype as six of his seven healthy siblings, and thus we predict that he is unaffected. These family studies are a novel application of an emerging genetic technology. DNA linkage analysis is useful for elucidation of the CF genotype in families where the clinical features are equivocal and management is an issue. PMID- 2311312 TI - Stimulation of duodenal muscle contraction by porcine or canine motilin in the dog in vivo. AB - Motilin is a 22 amino acid polypeptide stimulating intestinal muscle contraction. Structure analysis of motilin purified from hog and from dog intestinal mucosa reveals different amino acids in positions 7, 8, 12, 13, and 14. Previous in vitro experiments suggested this species-related structural heterogeneity could generate different bioactive characteristics for these two peptides. This study was designed to compare the stimulatory mechanism of canine and porcine motilins on dog duodenal motility in vivo, testing the hypothesis that canine motilin stimulates a receptor located on the intestinal muscle, while porcine motilin is acting on intrinsic nerves regulating intestinal muscle contraction. Synthetic porcine and canine motilins were administered through a catheter inserted in the caudal pancreatic duodenal artery to stimulate the contraction of a close irrigated duodenal segment. In acute experiments performed on anaesthetized animals, both peptides induced a similar motor stimulation that was inhibited by tetrodotoxin and atropine. In experiments in conscious animals, canine and porcine motilins were equally potent in inducing premature phase III of the migrating motor complex, and the action of both peptides was abolished by atropine or hexamethonium. This study reveals that the structural heterogeneity between porcine and canine motilin does not influence the bioactivity of both peptides in the dog in vivo and suggests that circulating endogenous motilin stimulates intestinal muscle contraction through intrinsic excitatory nerves. PMID- 2311314 TI - Twin gestation. PMID- 2311315 TI - Chronic pelvic pain. PMID- 2311313 TI - A new method for hemodynamic and echocardiographic assessment of conscious dogs: comparison with thiopental-morphine anaesthesia. AB - A method allowing assessment of cardiac structure and function in the conscious dog using readily available instrumentation is desirable and should provide physiologic advantages when compared to anaesthesia. Accordingly, we studied 19 dogs (22 +/- 2.5 kg), using two-dimensional echocardiographic and Swan-Ganz and femoral artery catheterization; ten were conditioned to permit conscious studies and nine received anaesthesia. Dogs receiving anaesthesia were induced with intravenous thiopental (16 +/- 4 mg/kg), followed by a maintenance dose (7 +/- 1 mg/kg/h) plus morphine sulphate (213 +/- 5 micrograms/kg/h). Cardiac index, mean blood pressure, and systemic vascular resistance were similar between groups. However, anaesthesia as compared to conscious studies resulted in a marked tachycardia (147 +/- 30 bpm, vs 98 +/- 19 bpm, p less than 0.0005), significantly lower right atrial pressure (5 +/- 2 mmHg vs 8 +/- 2 mmHg, p less than 0.05), and a trend towards a lower pulmonary capillary wedge pressure (6 +/- 5 mmHg vs 9 +/- 3 mmHg). Simultaneous echocardiography showed left ventricular diastolic cross sectional area to be smaller in the anaesthesia group (8.5 +/- 1.7 cm2 vs 10.4 +/ 1.5 cm2, p less than 0.05); however, ejection fraction in the two groups was similar. Velocity of circumferential fiber shortening (Vcf), normalized for heart rate and preload, was significantly lower in the anaesthetised dogs (0.63 +/- 0.22 circ/sec vs 0.89 +/- 0.26 circ/sec, p less than 0.05); this decline in Vcf, in association with a lower systolic wall stress (85 +/- 29 10(3) dynes/cm2 vs 119 +/- 23 10(3) dynes/cm2, p less than 0.05) indicates that thiopental-morphine anaesthesia depresses contractility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311316 TI - Nonsurgical management of chronic pelvic pain: a multidisciplinary approach. AB - Experience with multidisciplinary management of CPP has demonstrated the importance of ruling out and of treating nongynecologic conditions such as myofascial syndrome, irritable bowel syndrome, urethral syndrome, and psychogenic pain in women with CPP and normal laparoscopies. Moreover, current data suggest that availability of a multidisciplinary pelvic pain clinic can reduce the frequency of hysterectomy for this disorder. PMID- 2311317 TI - Tc-99m MDP bone imaging in inflammatory enthesopathy. AB - A case is presented in which uptake of Tc-99m MDP was noted at the sites of tendon and ligament attachments to the calcaneus in inflammatory enthesopathy. Following successful treatment with corticosteroids, the uptake was markedly decreased in accordance with subsidence of clinical manifestations and normalization of laboratory data. Radionuclide bone imaging may be useful in evaluating the response to treatment with corticosteroids as well as revealing the active disease sites in inflammatory enthesopathy. PMID- 2311319 TI - Diffuse uptake of osteotropic radionuclide in the breast secondary to superior vena caval obstruction. AB - Osteotropic radionuclide uptake in breast tissue has been described in a variety of benign and malignant lesions. The authors present a case of diffuse unilateral breast uptake secondary to neoplastic obstruction of the right brachiocephalic vein and superior vena cava. Following radiotherapy, the vascular obstruction resolved and the breast uptake was no longer observed. PMID- 2311318 TI - Accumulation of Tc-99m MDP in amyloidosis involving the tongue. AB - Radionuclide bone imaging using Tc-99m phosphates may show accumulation of activity in amyloid deposits. While many sites of amyloidosis have been detected with bone imaging, many reports center on cardiac amyloidosis. The case reported here demonstrates accumulation of Tc-99m MDP in amyloidosis involving the skin and muscle, including the tongue. PMID- 2311320 TI - Increased activity on radiocolloid scintigraphy in splenic hamartoma. AB - A higher uptake of radiocolloid in a splenic tumor than in the rest of the spleen was observed in a 17-year-old boy. The pathologic diagnosis of the surgically resected tumor was hamartoma composed of anomalous mixtures of splenic elements, and radiocolloid was considered to be distributed to reticuloendothelial cells in the tumor. Radiocolloid scintigraphy, which can demonstrate the function of the reticuloendothelial system, is helpful in the diagnosis of splenic hamartoma. PMID- 2311321 TI - Scintigraphic detection of bile leakage after cholecystectomy. PMID- 2311322 TI - Scintigraphic evaluation of septated hypokinetic gallbladder in a teenager. PMID- 2311323 TI - Arteriovenous malformation of the small bowel demonstrated during the flow phase of a Meckel's scan. PMID- 2311324 TI - 'Double right atrium' demonstrated by radionuclide ventriculography in cardiac transplantation. PMID- 2311325 TI - Dissociation between In-111 chloride and Tc-99m colloid bone marrow scintigraphy in refractory anemia with excess blasts. PMID- 2311326 TI - Extrapulmonary activity during perfusion lung imaging with Tc-99m MAA. PMID- 2311327 TI - Tc-99m white cell scintigraphy in suspected acute infection. AB - The usefulness of In-111 labeled white cells in acute infection is well documented but the role of Tc-99m labeled white cell scintigraphy (WCS) has not been as clearly established. Using stannous fluoride colloid and a simple labelling procedure with 20 ml of autologous whole blood, three cases are presented in which Tc-99m WCS established unexpected diagnoses in patients who had remained undiagnosed despite extensive investigation. PMID- 2311328 TI - Incidence of pulmonary embolism in elderly patients newly admitted to an acute geriatric unit: a prospective study. AB - To study the incidence of pulmonary embolism (PE) in elderly patients newly admitted to an acute geriatric unit, the authors carried out ventilation perfusion scans on 33 patients, 25 women and 8 men, mean age 79 years, consecutively admitted to the geriatric wards. The first scan was done within 5 days of admission and repeated between days 10 and 20. Where possible, patients with a positive second scan had a repeat scan at 2-3 months. Six (18%) patients were found to have a high probability of PE, 4 (12%) at the time of admission and two (6%) after admission. Three patients (9%) were considered to suffer from chronic pulmonary artery disease. Mortality was 5 for the whole group (15%) and 1 of 6 (17%) with a high probability of PE; this patient was suffering from carcinomatosis. The only patient who was anticoagulated suffered serious side effects. In no patient was PE clinically suspected. The authors conclude that PE is common in sick elderly patients newly admitted to acute geriatric wards, that rehabilitation with mobilization may precipitate new PE, and that nonanticoagulated PE does not seem to appreciably shorten the prognosis for life. Treatment with anticoagulants may be more dangerous than not treating PE in this older age group. PMID- 2311329 TI - Gallbladder perforation during liver biopsy diagnosed using hepatobiliary scintigraphy: a case report. AB - Serious complications of liver biopsy are uncommon with injury to the gallbladder being rare. Rapid diagnosis and proper management of injuries to the biliary system are necessary because of potential morbidity associated with bile peritonitis. Scintigraphy is an accepted means of evaluating traumatic injuries of the gallbladder and biliary tree. The authors present a case of iatrogenic perforation of the gallbladder during liver biopsy demonstrated by hepatobiliary scintigraphy. CT and surgical correlation are provided. PMID- 2311330 TI - Demonstration of abnormal peritoneal communication in patients with ascites. AB - Patients with ascites are known to have complications such as pleural effusions and hernias. Special diagnostic procedures are occasionally necessary to determine the nature of the abnormality and to determine the corrective medico surgical approach. The two cases described illustrate the usefulness of intraperitoneal as well as intrapleural injection of a radionuclide in diagnosing the leakage of ascitic fluid. PMID- 2311331 TI - Famotidine. Pharmacokinetic properties and suppression of acid secretion in paediatric patients following cardiac surgery. AB - The pharmacokinetic and pharmacodynamic properties of the H2-receptor antagonist famotidine have been well described in adult subjects. However, similar data for children are not available. Therefore, this study looked at the disposition of the drug (given to prevent aspiration following cardiac surgery) in 10 paediatric patients with normal kidney function (age range 2 to 7 years, bodyweight 14 to 25 kg) after a single intravenous dose of famotidine 0.3 mg/kg. Plasma concentrations of the drug and gastric pH values were both monitored for 20 hours by high performance liquid chromatography and aspiration of gastric juice, respectively. Plasma famotidine concentrations declined with an elimination half life of 3.3 +/- 1.8 h (mean +/- SD) and the drug was effective in elevating the gastric pH above 3.5 for about 9 hours in 6 patients. The variable volume of distribution and total plasma clearance of famotidine averaged 1.4 +/- 1.0 L/kg and 0.3 +/- 0.17 L/h/kg, respectively. In 4 patients unchanged famotidine could also be measured in a 12-hour urine fraction. The amount excreted (21 to 79%) correlated with clearance (r = 0.97). All these data are comparable to those obtained in healthy adults, indicating that paediatric patients receiving intensive medical treatment after cardiac surgery can handle famotidine in a way very similar to healthy adult subjects. A dosage of 0.3 mg/kg every 8 hours appears to be advisable. PMID- 2311332 TI - Scintigraphic study of radiolabelled interferon-alpha in osteosarcoma patients. AB - Interferon-alpha is currently under evaluation as an antineoplastic agent in several types of tumour. Despite its clear in vitro effects, the effectiveness of interferon in vivo is limited. To assess whether this discrepancy reflects pharmacokinetic limitations, the authors analysed interferon distribution in 2 osteosarcoma patients by scintigraphy using 123I-interferon-alpha-2a. Numerical analysis of the scintigraphic records demonstrated that the main organs of elimination were the kidneys, when the calculation was made on the basis of surface area. On the other hand, the apparent total uptake by liver (whose projection surface--i.e. the area exposed to the lens--is greater) was higher, reaching about 25 to 30% of the injected dose. The projection surface of the tumour was able to take up radiolabelled interferon in both cases, resulting in a 4-fold increase in the external radiation count compared with the equivalent region of the contralateral limb (although it is not possible to determine whether the label is present on the tumour itself or on the surrounding inflammatory cells). Thus, interferon-alpha seems able to reach at least the immediate neighbourhood of osteosarcoma mass. PMID- 2311333 TI - Polymorphism in hydroxylation of mephenytoin and hexobarbital stereoisomers in relation to hepatic P-450 human-2. AB - Stereoselective 4'-hydroxylations of R-(-)-mephenytoin and S-(+)-mephenytoin and 3'-hydroxylation of R-(-)-hexobarbital and S-(+)-hexobarbital were determined in liver microsomes of 14 Japanese subjects who were extensive metabolizers of mephenytoin and in five Japanese subjects who were poor metabolizers of mephenytoin. Content of P-450 human-2 assessed by Western blots was correlated to microsomal S-(+)-mephenytoin 4'-hydroxylation, R-(-)-hexobarbital 3' alpha hydroxylation, and S-(+)-hexobarbital 3' beta-hydroxylation, and was less correlated to R-(-)mephenytoin 4'-hydroxylation, R-(-)-hexobarbital 3' beta hydroxylation, and S-(+)-hexobarbital 3' alpha-hydroxylation. Antibodies raised against P-450 human-2 inhibited microsomal S-(+)-mephenytoin 4'-hydroxylation efficiently but was less efficient on R-(-)-mephenytoin 4'-hydroxylation in extensive metabolizers and on 4'-hydroxylation of mephenytoin enantiomers in poor metabolizers. The antibodies also inhibited R-(-)-hexobarbital 3' alpha hydroxylation and S-(+)-hexobarbital 3' beta-hydroxylation but did not effectively inhibit the hydroxylation of the two other optical isomers of hexobarbital in extensive metabolizers and of four stereoisomers in poor metabolizers. These findings indicate the close relationship between polymorphic mephenytoin 4'-hydroxylation and two stereospecific hexobarbital hydroxylations, and they suggest that P-450 human-2 is a typical S-(+)-mephenytoin 4'-hydroxylase and a major hexobarbital 3'-hydroxylase in the livers of extensive metabolizers. The findings were further supported by the experiments that used P-450 human-2 complementary dexoyribonucleic acid-derived protein in yeast microsomes. PMID- 2311334 TI - Clinical and pharmacokinetic properties of a transdermal nicotine patch. AB - We examined the pharmacokinetics of a transdermal nicotine patch and evaluated the usefulness of such a patch in a pilot smoking-cessation program. Use of the patch was associated with plasma nicotine concentrations that were comparable to smoking or to the use of other smoking-cessation devices. However, these plasma concentrations were maintained for 24 hours, and the patch appeared to be suitable for use once a day. Its use in a 6-week placebo-controlled double-blind study resulted in a significant degree of smoking cessation or in reduction of smoking activity. The findings suggest that it may be valuable to extend investigations to a larger population and that transdermal nicotine may have a useful role in smoking-cessation therapy. PMID- 2311335 TI - Binding of d-methadone, l-methadone, and dl-methadone to proteins in plasma of healthy volunteers: role of the variants of alpha 1-acid glycoprotein. AB - The plasma concentrations of alpha 1-acid glycoprotein (AAG), albumin, triglycerides, cholesterol, and total proteins, as well as the plasma binding of racemic, d-methadone, and l-methadone were measured in 45 healthy subjects. The AAG phenotypes and the concentrations of AAG variants were also determined. The measured free fractions for racemic, d-methadone, and l-methadone were, respectively, 12.7% +/- 3.3%, 10.0% +/- 2.9%, and 14.2% +/- 3.2% (mean +/- SD). A significant correlation was obtained between the binding ratio (B/F) for dl methadone and the total AAG concentration (r = 0.724; p less than 0.001). A multiple stepwise regression analysis showed that AAG was the main explanatory variable for the binding of the racemate. When concentrations of AAG variants were considered, a significant correlation was obtained between the binding ratio of dl-methadone and orosomucoid2 A concentration (r = 0.715; p less than 0.001), a weak correlation between dl-methadone and orosomucoid1 S concentration (r = 0.494; p less than 0.001), and no correlation between dl-methadone and orosomucoid1 F1 concentration (r = 0.049; not significant). Similar findings were obtained with the enantiomers. This study shows the importance of considering not only total AAG but also concentrations of AAG variants when measuring the binding of methadone and possibly of other drugs in plasma. PMID- 2311336 TI - Albendazole treatment of echinococcosis in humans: effects on microsomal metabolism and drug tolerance. AB - We prospectively studied the effect of albendazole on microsomal reserve and on first-pass activation to albendazole sulfoxide in patients with hydatid disease. An aminopyrine breath test was performed in 12 patients while they were receiving albendazole treatment and while they were not. Excretion of 14CO2 in breath averaged 0.70%.kg.mmol-1 +/- 0.20%.kg.mmol-1 without treatment and 0.54%.kg.mmol 1 +/- 0.14%.kg.mmol-1 with treatment (p less than 0.005). Plasma levels of albendazole sulfoxide were measured 4 hours after the morning dose during the first and second half of the 4-week treatment cycles. In nine of the 12 patients albendazole sulfoxide levels decreased during the second half of the cycle by an average of 0.84 +/- 0.76 mumol/L (p less than 0.02). Transaminase levels increased in 10 of the 12 patients during long-term albendazole treatment, and major side effects, including hepatotoxicity, neutropenia, and alopecia, were observed in three patients. We conclude that albendazole partially inhibits microsomal enzyme function but induces its own metabolism. Hepatotoxicity and other possible severe side effects necessitate close therapeutic monitoring of patients who are given albendazole. PMID- 2311337 TI - Severity of cirrhosis and the relationship of alpha 1-acid glycoprotein concentration to plasma protein binding of lidocaine. AB - The concentration of alpha 1-acid glycoprotein, the major determinant of the plasma protein binding of basic drugs, and the extent of lidocaine protein binding was related to the severity of liver disease in 30 cirrhotic patients. In comparison with matched control subjects, alpha 1-acid glycoprotein concentration (77 +/- 7 versus 37 +/- 3 mg/dl; mean +/- SEM; p less than 0.01) and lidocaine binding (69% +/- 2% versus 35% +/- 2%; p less than 0.01) was markedly reduced. There was a significant negative correlation (r = 0.78; p less than 0.01) between free lidocaine and alpha 1-acid glycoprotein concentration. Furthermore, both were significantly related to the severity of liver disease, as assessed by use of the Child Turcotte classification. PMID- 2311338 TI - Reproducibility of individual rates of ethanol metabolism in fasting subjects. AB - To estimate variability in ethanol metabolism, eight normal men received oral doses of 95% ethanol (1 ml/kg) after an overnight fast on each of 4 successive weeks. For each subject, slopes of linear decay curves of blood ethanol were highly reproducible--coefficients of variation ranged from 3% for the least variable subject to 12% for the most variable subject (mean, 8%). Compared to this low intraindividual variation, interindividual variation was slightly higher -the mean coefficient of interindividual variation was 14%, with a range from 10% to 17%. A one-way ANOVA with repeat measures showed that on any one of four separate occasions of ethanol administration, the eight subjects differed from one another (p less than 0.01), but that each subject remained similar from one test to another. The consumption of food before ethanol administration increased variability. Fever associated with upper respiratory infection also increased variability, but exercise did not. PMID- 2311339 TI - Influence of food on the pharmacokinetics of perindopril and the time course of angiotensin-converting enzyme inhibition in serum. AB - Food has been shown to reduce the bioavailability of the angiotensin-converting enzyme inhibitor captopril, but not the bioavailability of inhibitors administered as ester prodrugs. Perindopril is the ester pro-drug of the angiotensin-converting enzyme inhibitor perindoprilat. The influence of food on the pharmacokinetics of perindopril (4 mg administered orally) and the time course of angiotensin-converting enzyme inhibition in serum was studied in a randomized crossover short-term study of 12 healthy subjects. Food significantly decreased the relative availability of perindoprilat by 35% +/- 42%, the fractional urinary excretion of perindoprilat from 19% +/- 7% to 13% +/- 4% (p less than 0.05), and the partial metabolic clearance of perindopril to perindoprilat from 102 +/- 57 ml.min-1 to 72 +/- 32 ml.min-1 (p less than 0.05). These changes were associated with a significant decrease in the area under the percent angiotensin-converting enzyme inhibition-versus-time curve by 15% (p less than 0.05). Food did not alter the total amount of drug recovered in urine as perindopril and its metabolites, and it did not alter perindoprilat renal clearance. We concluded that food alters the conversion of perindopril to its active metabolite perindoprilat after single-dose administration of perindopril. PMID- 2311340 TI - Validation of the tolbutamide metabolic ratio for population screening with use of sulfaphenazole to produce model phenotypic poor metabolizers. AB - The present study has validated kinetically a convenient method to measure tolbutamide hydroxylation capacity in human beings by use of urinary metabolic ratios. The known in vivo and in vitro inhibitory properties of sulfaphenazole were used to convert control phase subjects to phenotypically "poor" metabolizers of tolbutamide. Six healthy subjects were given a single 500 mg oral dose of tolbutamide with and without sulfaphenazole, 500 mg every 12 hours. Tolbutamide, hydroxytolbutamide, and carboxytolbutamide in urine were determined by newly developed HPLC procedures. Plasma tolbutamide clearance and half-life were measured, as were the metabolic ratio (hydroxytolbutamide + carboxytolbutamide/tolbutamide) in successive 6-hour urine collections. The mean tolbutamide plasma clearance decreased from 0.196 +/- 0.026 ml/min/kg without sulfaphenazole to 0.039 +/- 0.009 ml/min kg with sulfaphenazole, and the mean half-life of tolbutamide increased from 7.28 +/- 0.89 hours to 38.76 +/- 13.30 hours. The metabolic ratio determined in the 6 to 12 hour urine collection period decreased from 794.0 +/- 86.6 to 126.0 +/- 79.3, and this collection period also gave the best separation of subjects between phases. There was a good correlation between tolbutamide plasma clearance and metabolic ratio (rs = 0.853, p less than 0.01, n = 12) and between the percentage decrease in plasma tolbutamide clearance and the percentage decrease in metabolic ratio (r = 0.932, p less than 0.01, n = 6). The tolbutamide urinary metabolic ratio therefore effectively distinguishes tolbutamide hydroxylase activity in "normal" subjects and in those converted to model phenotypically "poor" metabolizers by sulfaphenazole. PMID- 2311341 TI - Relationship between uptake and elimination of toluene and debrisoquin hydroxylation polymorphism. AB - The toxicokinetics of toluene were studied in six healthy subjects. Three of the subjects were phenotyped as rapid hydroxylators of debrisoquin and three subjects were phenotyped as slow hydroxylators of debrisoquin. The subjects were exposed in an exposure chamber to toluene vapor (3.25 mmol/m3) for 4 hours. Solvent concentrations in blood and the metabolites, hippuric acid and o-cresol, in urine were measured during the exposure period and 3 hours after exposure. The capacity to metabolize debrisoquin was determined in three volunteers who had earlier experimentally been exposed to toluene. The uptake of toluene was about 3 mmol, or 50% of the inhaled dose in both rapid and slow hydroxylators. There were no significant differences between the two phenotypic groups with regard to concentrations of toluene in blood, apparent blood clearance of toluene, or excretion of hippuric acid and o-cresol. PMID- 2311342 TI - Ketoconazole effects on corticosteroid disposition. PMID- 2311343 TI - Heterosexual spread of HIV. PMID- 2311344 TI - Histocompatibility antigens (A, B, C, and DR) in Arabs with rheumatoid arthritis. AB - Eighty-five Arab patients in Kuwait with classical and definite rheumatoid arthritis were typed to examine the frequency of HLA-A, B, C, and DR antigens. The results showed a significant increase in the frequency of HLA-A10, B8, B21, and DR3 antigens when compared to an age- and sex-matched control population. HLA DR3 was present in 34 per cent of the patients compared with 2 per cent of the controls (p less than 0.001). The association of RA in the Arab population with HLA-DR3 rather than HLA-DR4 or HLA-DR1 as reported in other ethnic groups emphasizes further the complexity of the genetics of RA. PMID- 2311345 TI - HLA antigens in Greek patients with cholelithiasis. AB - The distribution of HLA-A and B antigens was studied in 100 patients with cholelithiasis and in 202 healthy individuals all of Greek origin. An increased frequency of HLA-Aw19 was found in patients (33 per cent) compared with controls (22 per cent) (p less than 0.05, RR 1.7). The increase of Aw19 was even higher for patients with a family history of the disease (44 per cent, vs 22 per cent, p less than 0.01, RR 2.7) and for patients with cholesterol gall stones (44 per cent vs 22 per cent, p less than 0.01, RR 2.5). No difference was seen in patients without a family history of disease or with mixed gall stones. These results suggest a genetic basis for the development of cholesterol gall stone disease. PMID- 2311346 TI - HLA antigens associated with sarcoidosis. AB - In a series of 123 sarcoidosis patients (inhabitants of Moravia), frequencies of 15 HLA-A, 31 HLA-B, and 7 HLA-C antigens have been found. (Control group consisted of 500 healthy persons from the same region.) A subgroup of 46 patients was examined in order to determine a frequency of 10 HLA-DR antigens. (Control group consisted of 146 persons.) A positive association was proved between sarcoidosis and the HLA-B8 and B13 antigens (RR = 2.8 and RR = 3.1, respectively). A frequency of B8B13 heterozygotes was highly significant (RR = 8.5). The observed antigen genotype frequencies may be explained by the hypothesis of 2 HLA-linked disposing genes. PMID- 2311347 TI - HIV-infected cells are killed by rCD4-ricin A chain. PMID- 2311348 TI - Designing CD4 immunoadhesins for AIDS therapy. PMID- 2311349 TI - HTLV-1 polymyositis in a patient also infected with the human immunodeficiency virus. PMID- 2311350 TI - HIV viral sequences in seronegative people at risk detected by insitu hybridisation and polymerase chain reaction. PMID- 2311352 TI - Final regulations are published governing the National Practitioner Data Bank. PMID- 2311351 TI - HLA and celiac disease in Argentina: involvement of the DQ subregion. AB - A population of 62 unrelated homogeneous Argentinian celiac pediatric patients were typed for HLA-A,B,C,DR, and DQ antigens. The association between celiac disease and the DR3 and DR7 antigens was confirmed. The specificity DQw2 was present in 95.2 per cent of the patients. Nevertheless, it was of interest that the most significant phenotypes observed were DR3/DR7, DR7/DR5, and DR3/DR5. The significance of these findings is discussed. PMID- 2311353 TI - The Colorado WIC program. PMID- 2311354 TI - Countable entities: developmental changes. AB - The canonical countable entity for 3- and 4-year-old children is a discrete physical object. When children were asked to count labeled entities such as "forks", they counted each detached part of a fork as a separate entity. When asked to count kinds ("How many kinds of animals?") or properties ("How many colors?"), where each kind or property was exemplified by several separate objects, they included each discrete object in their count. Their counts of classes were more accurate in the absence of objects, or in the presence of a single member of each class, than in the presence of several members of each class. Young children are evidently predisposed to process discrete physical objects. Evidence is presented that, developmentally, this bias precedes learning to count. It is proposed that this discrete physical object bias facilitates mastery of counting. PMID- 2311355 TI - A computational learning model for metrical phonology. AB - One of the major challenges to linguistic theory is the solution of what has been termed the "projection problem". Simply put, linguistics must account for the fact that starting from a data base that is both unsystematic and relatively small, a human child is capable of constructing a grammar that mirrors, for all intents and purposes, the adult system. In this article we shall address ourselves to the question of the learnability of a postulated subsystem of phonological structure: the stress system. We shall describe a computer program which is designed to acquire this subpart of linguistic structure. Our approach follows the "principles and parameters" model of Chomsky (1981a, b). This model is particularly interesting from both a computational point of view and with respect to the development of learning theories. We encode the relevant aspects of universal grammar (UG)--those aspects of linguistic structure that are presumed innate and thus present in every linguistic system. The learning process consists of fixing a number of parameters which have been shown to underlie stress systems and which should, in principle, lead the learner to the postulation of the system from which the primary linguistic data (i.e., the input to the learner) is drawn. We go on to explore certain formal and substantive properties of this learning system. Questions such as cross-parameter dependencies, determinism, subsets, and incremental versus all-at-once learning are raised and discussed in the article. The issues raised by this study provide another perspective on the formal structure of stress systems and the learnability of parameter systems in general. PMID- 2311356 TI - The what and how of counting. PMID- 2311357 TI - What meaning postulates can do. PMID- 2311358 TI - Improving results with antidepressant drug therapy. PMID- 2311359 TI - Management of problems during menopause. AB - Many women pass through menopause with no problems and no complaints. They should be encouraged to pursue healthy life-styles. For those who do experience difficulties or for those who are at risk for developing problems, the aforementioned treatment options can be considered. At this time, the benefits of HRT appear to outweigh the risks and offer substantial improvement in the quality of life to appropriately selected women. With the realization that women can expect to live one third of their lives after menopause, it becomes clear that it is important to discuss menopausal health issues with each women in order to make the postmenopausal period as enjoyable as possible. PMID- 2311360 TI - New research in schizophrenia: implications for clinicians. PMID- 2311361 TI - Evaluation and treatment of chronic pain syndromes. PMID- 2311362 TI - The role of magnetic resonance imaging in the evaluation of spinal disorders. AB - Magnetic resonance imaging has rapidly evolved into the imaging method of choice for the majority of spinal disorders. Advances in MRI technology are continuing and should improve the diagnostic capability of the technique. If there is uncertainty about the diagnosis on the basis of MRI, however, the clinician should combine MRI with other studies such as CT scanning and/or myelography. PMID- 2311363 TI - Electroconvulsive therapy and the primary care physician: an update. PMID- 2311364 TI - Physiologic trend detection and artifact rejection: a parallel implementation of a multi-state Kalman filtering algorithm. AB - Using a parallel implementation of the multi-state Kalman filtering algorithm, we have developed an accurate method of reliably detecting and identifying trends, abrupt changes, and artifacts from multiple physiologic data streams in real time. The Kalman filter algorithm was implemented within an innovative software architecture for parallel computation: a parallel process trellis. Examples, processed in real-time, of both simulated and actual data serve to illustrate the potential value of the Kalman filter as a tool in physiologic monitoring. PMID- 2311365 TI - Exploring subjective vs. objective issues in the validation of computer-based critiquing advice. AB - Evaluation is an important part of the development of computer-based medical expert systems. Such evaluation may be particularly difficult when judging a critiquing system which responds to a proposed management strategy with a discussion of the advisability of that approach. DxCON is an expert system which produces a prose critique discussing the radiologic workup of obstructive jaundice. This paper describes DxCON, and its experimental validation by three independent judges. A central component of the validation involved allowing the judges to react to the system's advice in a quite flexible, unstructured fashion. This project provides a case study of how subjective issues impact both the design and implementation of a validation of a medical expert system whose output is explanatory prose. PMID- 2311366 TI - Analysis of jaw movements and masticatory muscle activity. AB - This paper describes software developed to analyze the temporal and spatial aspects of jaw movements, the speed, direction and magnitude of these movements in three dimensions, and the associated electromyograms (EMGs) of the masticatory muscles. Data from a subject chewing gum illustrates the software application. Manipulations of the stored digitized data are described. Temporal aspects of each chewing cycle are defined by specified delimiters for the beginning and ending of jaw opening and closing; spatial aspects are quantified by measurements derived from movement trajectories; and peak and mean velocities are derived from the velocity profiles. EMGs are digitized, rectified, averaged and referenced to jaw movement. Onset latencies, burst durations, rise times to peak activity, time of occurrence of peak activity, and amplitudes of peak and mean activities are measured from the EMGs. This detailed kinematic/EMG analysis provides previously inaccessible information about jaw muscles and the movements they control. PMID- 2311367 TI - Lung function analysis and optimization during artificial ventilation. A personal computer-based system. AB - In an intensive care unit a personal computer (PC) application for lung function analysis has been in use for 5 years. The PC system is applied to measure conventional and new parameters for diagnosis and therapy. The primary goal was to find parameters which could be used as optimization indices in optimal control systems for mechanical ventilation. Another clinical application of the PC system was as an automatic controller that stabilizes end-tidal CO2 concentration. The controller and the next application, the optimizer, could be integrated into an optimal control system. Such a system is described and a simulation trial of the integrated structure has demonstrated the potential. PMID- 2311368 TI - ONCHOSIM: a model and computer simulation program for the transmission and control of onchocerciasis. AB - ONCHOSIM is a computer program for modelling the transmission and control of the tropical parasitic disease onchocerciasis, or river blindness. It is developed in collaboration with the Onchocerciasis Control Programme in West Africa (OCP), and is used as a tool in the evaluation and planning of control operations. The model comprises a detailed description of the life history of the parasite Onchocerca volvulus and of its transmission from person to person by Simulium flies. The effects of different control strategies, based on larvicide application and chemotherapy (ivermectin), on the transmission and on the disease symptoms can be evaluated and predicted. In the program two simulation techniques are mixed. Stochastic microsimulation is used to calculate the life events of individual persons and inhabitant parasites, while the dynamics of the Simulium population and the development of the parasite in the flies are simulated deterministically. Output of ONCHOSIM conforms to the format in which data collected by the OCP are reported. This enables detailed checking of model specifications against empirical data. Output can also consist of summarizing key indices for the intensity of onchocerciasis infection, which is especially useful for comparing the effectivity of control strategies. PMID- 2311369 TI - Recognition of cell surface modulation by elliptic Fourier analysis. AB - A development of elliptic Fourier analysis, consisting in an alignment of harmonics according to their clockwise or counter-clockwise rotation, resolves the discrepancy between calculated harmonic frequencies and observed morphological periodicities. The new technique is supported by consistent data of empiric and fractal contours, comparatively analyzed and visualized with and without harmonic alignment. The method is particularly suitable for the recognition of periodic modulations of the cell surface. A preliminary analysis of two different cell populations (echinocytes and chondrocytes) shows distinct patterns of surface modulation that allow an effective discrimination of the cell type, while providing relevant information about the respective cytological configurations. PMID- 2311370 TI - Computerised algorithm of tumour-associated markers to monitor haematopoietic malignancy. AB - Hexosaminidase, polyamines and lipid-bound sialic acid are a few tumour associated markers which are significantly elevated both in urine and serum of patients with haematopoietic malignancy, in direct correlation to dedifferentiation. Our computer database incorporates these parameters and predicts the clinical response based on the baseline values of these tumour associated markers. This completely menu-driven user-friendly database can be routinely applied in tumour management and can access a billion records. The results of our evaluation confirm that most clinical assessments by a physician working blind are in agreement with the computer prediction, thus encouraging the use of microcomputers in patient management. PMID- 2311371 TI - Influence of estradiol on duration of anestrus and incidence of short estrous cycles in postpartum cows. AB - The influence of exposure to exogenous estradiol on the interval from parturition to first ovulation, luteinizing hormone (LH) secretion and luteal function was examined in cows. Cows were assigned at parturition to one of three treatments. Cows received either a 3.0 (1-E; n = 30) or .75 cm (1/4-E; n = 28) implant containing 17 beta-estradiol or served as untreated control animals (C; n = 33). Implants were administered within 2 days following parturition and removed on day 40 postpartum (day 0 = day of parturition). Single blood samples were collected twice weekly and analyzed for progesterone to determine length of postpartum anestrus and duration of the initial increase in progesterone. Sequential blood samples were collected on day 35 +/- .1 postpartum (15 min intervals for 18 hrs) from 5 cows in each treatment and analyzed for LH. Concentrations of estradiol were higher (P less than .01) in the 1-E (5.3 +/- .24) than in C (3.9 +/- .23) or 1/4 E (3.9 +/- .25) cows on day 35 postpartum. The interval from parturition to the first estrous cycle of normal duration was similar for cows in the C and 1-E treatment (53 +/- 2.4 and 56 +/- 2.4 days, respectively). Cows in the 1/4-E treatment had a longer (P less than .05) interval (68 +/- 2.5 days). Secretion of LH was similar among treatments on day 35 postpartum. The first normal luteal phase after parturition was preceded by a transient rise in progesterone in 81, 64 and 85% of the cows in the C, 1-E and 1/4-E treatments, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311372 TI - Influence of catecholamines, prostaglandins and thyroid hormones on growth hormone secretion by chicken pituitary cells in vitro. AB - In young chickens plasma concentrations of growth hormone (GH) are depressed by prostaglandins (PG) E1 and E2, epinephrine, norepinephrine, alpha 2 and beta agonists or thyroid hormones. A primary culture of chicken adenohypophyseal cells was used to examine the direct effects of these agents at the level of the pituitary as evaluated by GH release in the presence and absence of growth hormone releasing factor (GRF). Following collagenase dispersion and culture (preincubation, 48 hr) cells were exposed (incubation, 2 hr) to test agents, except for thyroid hormones which were added during the preincubation, and incubation period. Growth hormone release was increased (P less than .05) in the presence of PGE1 (10(-8)M by 34%; 10(-7)M by 54%), PGE2 (10(-8)M by 29%; 10(-7)M by 29%), PGF2 alpha (10(-8)M by 28%), and the beta agonist isoproterenol (10(-7)M by 46%). Basal GH release from chicken pituitary cells was not affected by dopamine, norepinephrine, epinephrine, thyroxine (T4), triiodothyronine (T3), or alpha adrenergic agonists. Growth hormone releasing factor stimulated GH release was not affected by the presence of prostaglandins E1, E2 or F2 alpha in the incubation media. However, GRF stimulated GH release was reduced by high doses of catecholamines: dopamine (10(-6)M by 34%), norepinephrine (10(-6)M by 74%), epinephrine (10(-8)M by 47%; 10(-7)M by 41%; 10(-6)M by 89%), and by the alpha 1 adrenergic agonist, phenylephrine (10(-7)M by 52%), the alpha 2 agonist, clonidine (10(-8)M by 34%; 10(-7)M by 83%) and the beta agonist, isoproterenol (10(-7)M by 64%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311373 TI - Effect of bovine somatotropin on the growth rate, hormone profiles and carcass composition of Holstein bull calves. AB - A study was conducted to determine the effects of BST on the growth rate, hormone profiles and carcass composition of preweaned Holstein bull calves. Injection of BST resulted in increased average daily gains and feed intakes (P less than .05) compared to that of control animals. This increased rate of gain coupled with increased intakes resulted in identical feed conversion efficiencies between treatments. Fractional weights (organ weight/body weight) of selected organs and tissues were unaffected by BST treatment. Carcass fat percentage was reduced in BST-treated calves (28.1 +/- 1.18% and 32.8 +/- 1.84% for BST and controls groups respectively, P less than .05) while no differences were seen for carcass DM, CP, ash or gross energy content. Plasma BST levels were higher (P less than .0001) in BST treated calves while plasma IGF-1 levels were not different between treatments. Plasma IGF-1 concentrations correlated (P less than .0001, R = .71) with average daily gains. The results of this trial suggest that growth responses are inducible with BST in young calves (7 days to 3 months). PMID- 2311374 TI - Molecular forms of gastrin in antral mucosa of the horse. AB - The predominant form of gastrin in the antral mucosa of the stomach of virtually all species previously examined is the 17 amino acid peptide little gastrin (G17). This report describes the occurrence in equine antral mucosa of an immunoreactive form of gastrin with elution properties on Sephadex G-50 superfine similar to human unsulfated big gastrin (G34-I). This putative equine big gastrin was a major component of the gastrin immunoreactivity present. A second peak of activity in equine antral mucosa eluted in an identical manner to human little gastrin (hG17-I). Inhibition curves of equine big and little gastrin, with the gastrin radioimmunoassay utilized in this study, were parallel. This observation indicates that there was no spurious increase in the apparent relative amount of big gastrin due to significant differences in the RIA antibody cross-reactivity to big and little equine gastrin. The equine big gastrin peak was resolved by ion exchange chromatography into unsulfated and sulfated forms in approximately equal amounts. This data implies that posttranslational processing of gastrin in horses may differ from that of species previously studied. PMID- 2311375 TI - Comparisons of endocrinological and testis parameters in 18-month-old Ile de France and Romanov rams. AB - Endocrinological and testis parameters of adult 18-month-old Ile de France (IF) and Romanov (Ro) rams were compared during sexual season. Testis weights, total volumes of intertubular tissue, and of blood and lymph vessels, total seminiferous tubule length, rete testis flow rate and daily production of germ cells were significantly higher in IF than in Ro rams. These variations originated from differences in Sertoli cell numbers, which were established before puberty. When daily productions of germ cells, of ABP or of RTF were expressed per Sertoli cell, they were higher in Ro than in IF rams. Quality of spermatids, as measured by their cellular size prior to elongation, was lower in Ro than in IF. The number of FSH-binding sites per Sertoli did not differ between the two breeds but FSH plasma levels were higher in Ro than in IF rams. Total numbers of Leydig cells per testis, their individual size or their LH-binding capacity did not differ significantly between the two breeds. However, the ratio of mean testosterone upon mean LH plasma levels were greater in Ro than in IF rams while both breeds had identical LH mean plasma levels. PMID- 2311377 TI - DSM-III and DSM-III-R schizotypal symptoms in borderline personality disorder. AB - The frequency of DSM-III and DSM-III-R schizotypal personality disorder (SPD) symptoms and diagnosis was explored in 39 inpatients classified as borderline by the Diagnostic Interview for Borderlines (DIB) and 19 inpatient major depressive disorder (MDD) controls. Most SPD symptoms in all groups, except the nondepressed borderlines, derived from social-interpersonal items. By DSM-III, 24 borderlines (62%) but only six controls (32%) had cognitive-perceptual SPD symptoms (P = .03), whereas by DSM-III-R only 14 borderlines (36%) and seven controls (37%) had such symptoms. Of the 24 borderlines showing cognitive-perceptual symptoms, 16 also had MDD, a significant difference from the non-MDD borderlines (P = .04). This difference disappears in DSM-III-R. The results suggest that some SPD symptoms in borderlines may be related to a concurrent affective episode. PMID- 2311376 TI - Changes in follicular endocrinology during final maturation of porcine oocytes. AB - Thirty-one gilts were ovariectomized between 21 and 34 hr after the onset of estrus to compare changes in follicular endocrinology with stages of oocyte maturation. Oocytes were recovered from 6 to 8 mm follicles and classified by stage of meiosis. Remaining follicular fluid was assayed for steroids and dermatan sulfate. Amounts of prostaglandin F2 alpha (PGF2 alpha) and E2 (PGE2) were measured in intramural tissues. Coincident with germinal vesicle breakdown, the follicular content of all steroids except testosterone decreased (P less than .05). As oocytes approached metaphase II, the amount of progesterone within follicles increased (P less than .05), and estradiol continued to decrease (P less than .05). The pattern of dermatan sulfate content was biphasic and peaked at germinal vesicle breakdown and anaphase stages. Amounts of PGF2 alpha and PGE2 within intramural tissues increased (P less than .05) throughout oocyte maturation. Follicular atresia was evident during estrus; however, more (P less than .05) atretic follicles were recovered at germinal vesicle than metaphase II stages (20 vs 3%, respectively). Follicular development, within a gilt, was skewed (P less than .05) and classification of follicles by hormone content demonstrated that a majority were more mature than a minority of less mature follicles. These data suggest that follicular maturation and oocyte development are highly correlated in swine. Furthermore, partitioning the follicular variability by hour and stage of oocyte maturation allowed for more precise assessment of follicular endocrinology than previously reported. PMID- 2311378 TI - Schneiderian symptoms in multiple personality disorder and schizophrenia. AB - We report structured interview data from a series of 102 cases of multiple personality disorder (MPD) diagnosed in four centers. Schneiderian first-rank symptoms of schizophrenia were equally common in all four centers. The average MPD patient had experienced 6.4 Schneiderian symptoms. When these 102 cases are combined with two previously reported series of MPD cases, an average of 4.9 Schneiderian symptoms in 368 cases of MPD is noted. This compares with an average of 1.3 symptoms acknowledged by 1,739 schizophrenics in 10 published series. Schneiderian symptoms are more characteristic of MPD than of schizophrenia. PMID- 2311379 TI - Proximal spacing to facial affect expressions in schizophrenia. AB - Schizophrenics (N = 40), depressives (N = 36), anxiety neurotics (N = 35), and nonpatient controls (N = 60) were asked to walk forward from a distance of 10 feet to a distance comfortable for possible interaction with facial expressions of six affects and a neutral state, depicted in life-sized images. Schizophrenics demanded significantly greater proximal space than other groups to interact with facial affect expressions, especially the nonaroused ones (happy, sad, neutral state). Multiple discriminant analysis of the "comfortable interaction distance" data revealed that schizophrenic persons may be discriminated with moderate accuracy (52.5%) from other groups. PMID- 2311380 TI - Clinicians' practices in personality assessment: does gender influence the use of DSM-III axis II? AB - We assessed clinicians' practices in the process of personality assessment according to DSM-III axis II criteria. Forty-six clinicians rated personality traits and disorders on two versions of a clinical profile constructed to meet DSM-III axis II diagnoses of histrionic, narcissistic, borderline, and dependent, differing only in the sex of the patient. Clinicians tended to use only a single diagnostic category and to make significantly different personality attributions and diagnoses depending on the patient's sex. The sex of the clinician had no impact on the process. We conclude that clinicians viewing a case study tend to make global judgments about personality disorders and are influenced by the patient's gender, even when it has no known relevance. We interpret these findings in terms of critical set theory. PMID- 2311381 TI - Development of a scale for the measurement of symptom change in an outpatient clinic. AB - A brief 21-item symptom rating scale, the Psychiatric Outpatient Rating Scale (PORS), was developed for use in outpatient clinics. On the basis of its initial use with 86 patients, it was shown to have high internal and interjudge reliability and evidence of concurrent and construct validity. Scores on the PORS correlated significantly with the Global Assessment Scale and with the number of sessions of psychotherapy. For a subsample of 45 patients rated on the PORS at the beginning and termination of psychotherapy, seven symptoms revealed highly significant improvement. The PORS appears to be a potentially useful measure of change in outpatient clinics. PMID- 2311382 TI - Atypical anxiety disorder: a descriptive study. AB - This retrospective study examined 75 outpatients who received an atypical anxiety disorder diagnosis in a 30-month period. Patients who were later rediagnosed tended to have multiple anxiety diagnoses. "Atypical," in this sense, meant that insufficient information was available to arrive at specific anxiety diagnoses. A subgroup that continued to be diagnosed as atypical throughout their treatment tended to have multiple subsyndromal complaints, unusual symptoms, or both. This subgroup raises questions regarding the cutoff criteria for the anxiety disorders in DSM-III and DSM-III-R and suggests a possible new diagnostic subtype for future investigation. PMID- 2311384 TI - Bulimia nervosa with and without a history of anorexia nervosa. AB - This study compared two subgroups of women of normal weight with bulimia nervosa: those with a history of anorexia nervosa and those without such a history. Those with a history of anorexia nervosa indicated a desired body weight significantly lower than those without the history. Those with a history of anorexia nervosa were more likely to abuse laxatives and less likely to self-induce vomiting. Both groups reported feeling fat and worrying a great deal about weight and shape issues. PMID- 2311383 TI - Symptom and comorbidity patterns in World War II and Vietnam veterans with posttraumatic stress disorder. AB - Forty-four veterans with posttraumatic stress disorder (PTSD) from World War II and Vietnam were compared. The groups were comparable on many socioeconomic and combat measures and age at onset of PTSD. Vietnam veterans exhibited more severe PTSD symptoms, higher Hamilton depression scores, and higher scores on the hostility, psychoticism, and "additional symptom" Symptom Checklist-90 (SCL-90) scales. They also had more survivor guilt, impairment of work and interests, avoidance of reminders of trauma, detachment/estrangement from others, startle response, derealization, and suicidal tendencies. Differences were noted between the groups as to the nature of upsetting experiences. Vietnam veterans had a greater lifetime frequency of panic disorder and an earlier age of onset for alcoholism. In other respects, the two groups were diagnostically similar, with PTSD being related to the sequential emergence of psychiatric diagnoses in similar manner for World War II and Vietnam patients. PMID- 2311385 TI - Who smokes? Why?: Psychiatric aspects of continued cigarette usage among lawyers in Washington State. AB - Eight-hundred two lawyers, a random sample of the Washington State Bar, were surveyed to determine the prevalence of medical and psychological distress. Approximately 15% of this group reported current cigarette use. Greater levels of dysphoric symptoms and greater misuse of alcohol differentiated male smokers from male nonsmokers, whereas no differences were found for females. The implications of these findings for pharmacologic and counseling strategies to further promote smoking cessation are discussed. PMID- 2311386 TI - Predicting outcome of schizophrenia: significance of symptom profiles and outcome dimensions. AB - To clarify the antecedents of poor long-term outcome in schizophrenia, 58 DSM-III diagnosed schizophrenic inpatients, mostly chronic, were prospectively assessed on psychiatric symptoms and background variables. The 46 patients (79.3%) who could be relocated after 1 to 4 years (mean, 2.7 years) were evaluated on a multidimensional outcome scale and days of subsequent hospitalization. We found, contrary to prevailing belief, that a baseline positive, not negative, syndrome predicted poor outcome. Thought disturbance portended the worst prognosis and depressive syndrome the best. Multiple regression analysis showed (a) reliable prediction for 9 of 10 outcome measures (r values from .49 to .61); (b) separate contributions by clinical, genealogical, and historical predictors; and (c) different sets of variables that predicted social v occupational adjustment. The results have implications for prognosis, rehabilitation planning, and understanding of the obstacles to successful transition to community living. PMID- 2311387 TI - Computing. Get with it. PMID- 2311388 TI - Oral hygiene and dental care. PMID- 2311389 TI - Foot and leg care. PMID- 2311390 TI - Follow-on milks. PMID- 2311391 TI - Quality assurance in antenatal care. PMID- 2311392 TI - Education: future perfect? PMID- 2311393 TI - Extending health. PMID- 2311394 TI - Community liaison. Life's rich pattern. PMID- 2311396 TI - Silent epidemic. PMID- 2311395 TI - Computing. Mapping community health. PMID- 2311397 TI - Therapeutic drug monitoring of cyclosporine (CSA). PMID- 2311398 TI - Needles and syringes. Department of Consumer Protection. PMID- 2311399 TI - Study of the Canadian health care system. AMA Board of Trustees. PMID- 2311400 TI - Connecticut emergency department physicians survey. Implications for graduate medical education. AB - A survey conducted in mid-1989 of 36 Connecticut hospital emergency departments sought to determine the nature of physician staffing and the volume and the acuteness of patient problems. Overall, only 31% of emergency department staffing is provided by board certified emergency physicians in the state of Connecticut. In addition to emphasizing the lack of board certified emergency physicians available in the state, this survey also indicated a relative deficiency in emergency department physician staffing in general with approximately 20% of all positions currently unfilled statewide. The implications of these findings for graduate medical education in Connecticut are discussed. PMID- 2311401 TI - More on podiatric surgery. PMID- 2311402 TI - Low dose streptokinase for acute myocardial infarction in a community hospital. PMID- 2311403 TI - Effect of verapamil on different spermatozoal functions in guinea pigs--a preliminary study. AB - Verapamil, a calcium channel blocker, was administered orally using three different doses to guinea pigs. Both short-term (4 weeks) and long-term (12 weeks) effects of the drug were observed. The drug administration resulted in a marked decrease in sperm density, sperm motility and cellular energy content (ATP). Zona pellucida penetration by the sperm obtained from drug-treated animals was significantly lower when compared with sperm from normal animals. Histopathological findings exhibited partial arrest of spermatogenesis. Partial to complete recovery was observed after 4 and 6 weeks of withdrawal of the drug treatment. PMID- 2311404 TI - Ovulation blockade through synergism of cycloheximide with assorted anesthetics. AB - This report addresses the following question: Can ovulation be blocked through a combined action of two drugs, which individually have no effect on ovulation. Ovulation blockade in hamsters was achieved through synergism of two drugs that individually had no effect on ovulation. Treatments were given at 18:00 h on pro estrus. The keystone finding was that cycloheximide (CX), in a dose too small to affect ovulation, can be made to block ovulation by pretreating hamsters 15 min earlier with pentobarbital. Ovulation blockade was also achieved with phenobarbital + CX, ketamine + CX, and ether + CX. When given alone, none of the four anesthetics interfered with ovulation. The mechanism by which the anesthetic/CX synergism works is not known. The pituitary can be excluded as a target, because it is not necessary for ovulation after 15:30 on pro-estrus. It is speculated that CX reduces the synthesis of ovarian proteins needed for follicle rupture, and the anesthetics augment this process through action on either the ovary, the brain, the liver, or a combination thereof. PMID- 2311405 TI - Effects of progesterone antagonist ZK 98.299 on early pregnancy and foetal outcome in bonnet monkeys. AB - The antiprogestin ZK 98.299 (onapristone) was injected subcutaneously (25 mg/day) for 4 consecutive days during early pregnancy to 8 bonnet monkeys. Retrospective analysis of the data showed that the treatment was initiated between 20 to 30 days after the mid-cycle peak in estradiol levels. In 7 animals, vaginal bleeding was induced within 3.6 +/- 2.7 days (mean +/- S.D.) after the initiation of treatment. However, pregnancy was terminated completely only in 5 animals. In these 5 animals, menstruation was induced 1 to 4 days after the initiation of treatment. Serum progesterone levels also decreased; however, a significant decrease (p less than 0.02) in mean levels was not observed until 5 days after the initiation of treatment. In the other 3 animals, in spite of some drop in serum progesterone levels after the treatment and slight vaginal bleeding in 2 animals, the pregnancy continued. Two animals delivered stillborn foetuses at term. The foetuses weighed 92 and 105 g, which is markedly lower than the normal foetal weight (345 +/- 48 g, n = 6) at birth. The gross appearance of the foetuses was suggestive of recent intrauterine foetal death. In the third animal hysterotomy was performed on day 65; foetus weighed 5 g. Haematoma and blood clots were seen in the placental tissue. This limited data on 8 animals demonstrates that ZK 98.299, at the dose regimen employed, completely terminates early pregnancy in 62% of animals. In the cases in which treatment failed, the pregnancy did not continue unaffected. The endocrine function of the placenta was affected and the foetal growth was retarded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311407 TI - Effects of enalapril on human sperm motility. AB - The angiotensin converting enzyme inhibitor, enalapril, reduced the motility of washed human spermatozoa. The concentrations producing 50% inhibition were: (percentage motility) 11.6 +/- 2.6 mM, (average forward velocity) 8.0 +/- 1.5 mM and (motility index) 8.5 +/- 2.1 mM (mean + s.e.m.). Enalapril 20 mM prevented all forward movement and reduced percentage motility to an extremely low level. Motility was reduced within 20 sec of addition and little further change occurred during a 60-min incubation period. Inhibition of percentage motility by enalapril was reversible with a 5-min washing procedure following a 5-min incubation period, but not following a 60-min incubation period. Enalapril 20 mM did not impair plasma membrane integrity (hypoosmotic swelling test) or viability (nigrosin-eosin stain). It is concluded that the antimotility effects of enalapril are not caused by inhibition of angiotensin converting enzyme, but may be of interest in the search for new spermicidal agents. PMID- 2311406 TI - Effect of alpha-chlorohydrin on in situ pH in rat testis and epididymis. AB - The effect of the male contraceptive, alpha-chlorohydrin, on in situ pH in seminiferous tubules and epididymal duct of the rat has been studied employing in vivo microelectrode techniques. After eight days of low-dose alpha-chlorohydrin administration (15mg/kg/day), a significant increase in acidity of luminal fluid in seminiferous tubules, proximal caput, middle caput, and proximal cauda epididymidis was observed. Increased acidity in the testis and epididymis may play an important role in the antifertility effect of alpha-chlorohydrin. PMID- 2311408 TI - Society of Critical Care Medicine, nineteenth annual educational and scientific symposium. San Francisco, California, May 29-June 1, 1990. Abstracts. PMID- 2311409 TI - Hypothermic preservation of hepatocytes. II. Importance of Ca2 and amino acids. AB - The importance of the components of a tissue culture media, Leibovitz-15 (L-15), for maintaining viability of hypothermically preserved hepatocytes was analyzed. Hepatocytes isolated from rat livers were incubated at 5 degrees C in an oxygenated environment with continuous shaking (to simulate organ perfusion preservation). L-15 + 5 g% polyethylene glycol (PEG) or variants of this solution were used as the preservation media. After 48 hr of storage, hepatocyte viability was assessed by measuring the release of LDH into the incubation medium and cell volumes were determined. Following 90 min of normothermic incubation (to simulate organ reperfusion), mitochondrial function was measured. Hepatocytes stored in the complete L-15 solution were about 90% viable at the end of 48 hr of storage, while cells stored in a solution containing only the principle electrolytes (PE) lost viability (70% viable). Only the addition of a combination of divalent cations (Ca/Mg) and amino acids was sufficient to maintain viability equivalent to that obtained in the complete L-15 mixture. Hepatocytes suspended in L-15 maintained normal cell volumes (3.85 microliters/mg protein), while cells in the PE solution were swollen with cell volumes of 4.66 microliters/mg protein. Only the addition of Ca/Mg to the PE solution was effective at suppressing cell swelling similar to the complete L-15 media. Both basal and uncoupler-stimulated respiration were depressed in cells stored in the PE solution (15 and 28 nmol O2/min/mg protein) as compared to cells in L-15 (21 and 41 nmol O2/min/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311410 TI - Cryopreservation of skin using a murine model: validation of a prognostic viability assay. AB - In order to evaluate the many variables that can affect cryopreservation success, a simple, highly reproducible model system is required. We have evaluated the use of tetrazolium reductase activity as a prognostic indicator of skin viability in an inbred murine model. Two inbred hairless mouse strains were characterized in studies on autografting and allografting following different skin-storage protocols. Skin tetrazolium reductase (TR) activity correlated well with oxygen consumption, and with graft success--the ultimate performance criterion- following varying degrees of cryogenic injury. The assay was shown to be highly reproducible. In a series of factorial experiments the only factors affecting TR activity were those concerning the mouse donors, i.e., mouse strain, age, sex, and body area. The effects of these factors on TR activity were fully characterized. PMID- 2311411 TI - Propane-1,2-diol as a potential component of a vitrification solution for corneas. AB - Any method of cryopreservation of the cornea must maintain integrity of the corneal endothelium, a monolayer of cells on the inner surface of the cornea that controls corneal hydration and keeps the cornea thin and transparent. During freezing, the formation of ice damages the endothelium, and vitrification has been suggested as a means of achieving ice-free cryopreservation of the cornea. To achieve vitrification at practicable cooling rates, tissues must be equilibrated with high concentrations of cryoprotectants. In this study, the effects of propane-1,2-diol on the structure and function of rabbit corneal endothelium were studied. Corneas were exposed to concentrations of propane-1,2 diol ranging from 10 to 30% v/v in a Hepes-buffered Ringer's solution containing glutathione, adenosine, 5 mmol/liter sodium bicarbonate, and 6% w/v bovine serum albumin. Endothelial function was assessed by monitoring corneal thickness during perfusion of the endothelial surface at 34 degrees C for 6 hr. Exposure to 10-15% v/v propane-1,2-diol was well tolerated for 20 min at 4 degrees C when the cryoprotectant was removed in steps or by sucrose dilution. However, exposure to 25% v/v propane-1,2-diol for 20 min at 0 or -5 degrees C was consistently tolerated only when 2.5% w/v chondroitin sulfate was included in the vehicle solution. Exposure to 30% v/v propane-1,2-diol was harmful at -5 and -10 degrees C. The endothelial damage following exposure to 30% v/v propane-1,2-diol was probably the result of a toxic effect rather than osmotic stress. Although 25% v/v propane-1,2-diol does not vitrify at cooling rates that are practicable for corneas, it could at this concentration form a major component of a vitrification solution comprising a mixture of cryoprotectants. PMID- 2311412 TI - The process of freezing and the mechanism of damage during hepatic cryosurgery. AB - Experiments were performed to correlate the structures of liver tissue frozen during cryosurgery, liver frozen at various constant cooling rates, and unfrozen, dried normal liver. The results show that during freezing of tissue ice forms and propagates along the vascular system, expanding during freezing at low cooling rates. This expansion occurs over most of the region frozen during cryosurgery and may be one of the mechanisms of damage to tissue during cryosurgery. PMID- 2311413 TI - Effect of continuous versus multiple intermittent light exposures on rat retina. AB - The damaging effects of continuous light exposure to the albino rat retina have been well documented. However, the cumulative effects of multiple light exposures are not well defined. We therefore compared the retinal injury induced by a single 24 hour light exposure with that caused by three intermittent exposures of 8 hours each. Eight dark-adapted albino Lewis rats were exposed for 24 hours to green fluorescent light (490-580 nm) at an illuminance level of 175 foot-candles. A second group of 8 rats was exposed under similar conditions in three split doses of 8 hours each at intervals of 7 days between each exposure. Recovery was allowed in total darkness, and the animals were sacrificed 2 weeks following the last exposure. Retinal damage was assessed by morphometry and light and electron microscopy. Mild cumulative retinal injury, mostly in photoreceptor cells with relative sparing of the retinal pigment epithelium, was seen in the split dose group, while extensive damage involving photoreceptor cells and retinal pigment epithelium was noted in the group exposed continuously for 24 hours. PMID- 2311414 TI - Calpain and calpastatin in rabbit corneal epithelium. AB - The purpose of this study was to provide a direct assay for calpain and its endogenous inhibitor calpastatin in normal rabbit epithelium. Corneal epithelial extracts were fractionated by DEAE (1) chromatography on HPLC. Fractions were analyzed for calpain by ELISA, immunoblotting, and caseinolytic enzyme activity with FITC-labeled casein. Results demonstrated immunoreactive peaks for calpains I and II. Calpain II from the soluble fraction of corneal epithelium eluted at a similar NaCl concentration (260 mM) as calpain II from other tissues, was inhibited by both E64 and the removal of Ca, contained an 80 kDa subunit in immunoblots, and was present at specific activity of 220 units/g protein (in a crude homogenate). Calpain antigen was also present in the EDTA/EGTA washed insoluble fraction of corneal epithelium. Calpastatin in corneal epithelium eluted at 130 - 160 mM NaCl on DEAE, coeluted with calpain I, and was present at 330 units/g protein (crude homogenate). The results demonstrated a calpain/calpastatin system in corneal epithelium, where it is speculated to play a role in epithelial cell turnover and wound healing. PMID- 2311415 TI - Effect of glycoconjugates on rod outer segment phagocytosis by retinal pigment epithelial explants in vitro assessed by a specific double radioimmunoassay procedure. AB - Rod outer segment (ROS) phagocytosis by explanted bovine retinal pigment epithelium (RPE) was evaluated by a procedure using an indirect double radioimmunoassay which distinguished between ROS attached to the RPE cell surface and those which had been ingested. This approach has been used to investigate the effect of a variety of glycoconjugates on the phagocytic process. Inclusion of the glycosaminoglycans (GAGs) chondroitin sulphate type-A (CS-A) and type-C (CS C), hyaluronic acid (HA) or dermatan sulphate (DS) in the incubation medium significantly inhibited the ingestion phase of ROS phagocytosis, whereas the binding phase was inhibited to a lesser extent. The interphotoreceptor matrix (IPM), containing these GAGs as part of proteoglycans, also had an inhibitory effect on phagocytosis. The free monosaccharides mannose, fucose and galactose all stimulated the ingestion of ROS by RPE cells. These findings support the suggestion that glycoconjugates may have a physiological role in the photoreceptor renewal process. PMID- 2311416 TI - Epidermal growth factor in human tear fluid: increased release but decreased concentrations during reflex tearing. AB - To further clarify the role of epidermal growth factor (EGF) in the physiology and pathophysiology of the ocular surface the effects of reflex tearing on concentrations of EGF in tear fluid were studied. Tear fluid samples were collected with glass capillaries before (basal samples, 59 eyes, 30 individuals) and during reflex tearing (stimulated samples, n = 212, 40 eyes, 20 individuals). The rate of tear fluid flow in the capillaries (TFFc) was measured. The concentrations of human EGF (hEGF) was determined by time-resolved immunofluorometric assay (TR-IFMA). The first basal samples contained higher concentrations of hEGF than the samples from the contralateral eyes (n = 28) collected thereafter (p less than 0.05). The basal samples from 40 eyes contained a significantly higher mean concentration of hEGF (8466 pg/ml) than did the stimulated samples (n = 212, 2763 pg/ml); p less than 0.001). The mean TFFc increased from 63 nl/s to 506 nl/s during reflex tearing (p less than 0.001) and the amount of hEGF released from 567 fg/s (n = 40) to 1400 fg/s (n = 212; p less than 0.001). Basal samples from females contained higher concentrations of hEGF than did those from males. The maintenance of the hEGF concentration at a certain level and the increased amount of hEGF released into the tear fluid during reflex tearing suggests continuous release of hEGF into tear fluid from the lacrimal gland. PMID- 2311417 TI - Adjunctive drug use among opiate addicts. AB - In a study of 249 opiate (mainly heroin) addicts special attention was paid to adjunctive drug use. Generally, nicotine (cigarette smoking), alcohol and cannabis preceded the use of heroin, and continued to be used as adjunctive drugs after the establishment of heroin addiction. Nicotine was the most common substance used together with opiates. Alcohol and cannabis were used as adjunctive drugs in about two-thirds of the cases. In the late stages of heroin addiction, benzodiazepines were also used concomitantly with opiates. The most frequently reported reason for the use of adjunctive drugs was to intensify the effect of the opiate. Three-quarters or more of the addicts had used different adjunctive drugs to boost the euphoric feeling derived from the primary drug, i.e. heroin. Attempt at self-treatment of withdrawal symptoms was a less frequently reported reason for adjunctive drug use. The findings show that heroin addiction is the major problem. The use of adjunctive drugs, especially benzodiazepines, can be partly explained on economic grounds. They must be clearly distinguished from the primary drug of abuse, heroin. For policy-making decisions, it is important that the elimination of heroin abuse through effective prevention measures would ultimately wipe out the problem of adjunctive drug use, while reduction of the overall supply of heroin without reduction in actual demand might result in an increasing trend to adjunctive drug use. PMID- 2311418 TI - Perineal necrotizing infection. PMID- 2311419 TI - The surgical care of centenarians. PMID- 2311420 TI - Endoscopic sclerosis prevents experimental reflux for longer than 12 months: reinforcement of the gastric component of the reflux barrier? PMID- 2311421 TI - The effect of coronary collateral recruitment on ventricular recovery after brief coronary occlusion in dogs and pigs. PMID- 2311422 TI - Response of the transplanted lung to particulate antigen. PMID- 2311423 TI - The effects of argon laser on bovine aortic endothelial and smooth muscle cell proliferation and collagen production. PMID- 2311424 TI - Correlation of anaphylatoxin levels and survival with bacteremia and endotoxemia in the first 2 hours after trauma. PMID- 2311425 TI - Attachment of growth factors to implantable collagen. PMID- 2311427 TI - Perineal necrotizing infection. AB - Perineal necrotizing infection is a severe disease that ever since its first description by Fournier in 1883 has been referred to by many names prompted by its protean nature in terms of location and suspected etiology. We treated nine patients with PNI. The infection began as a perineal abscess of long evolution (7 days +/- 2 SD) in eight patients. The ninth patient had had an inguinal herniorrhaphy 3 days before. The cultures of the exudates and tissues always yielded aerobic and anaerobic mixed flora of colorectal origin, except in one instance, in which S. aureus and hemolytic streptococcus A were identified. The treatment was medical support and wide surgical debridement of the infected tissues. In six patients a left transverse colostomy was performed. Only one patient died, of septic shock. On the basis of the results in our series and on a review of the literature, it is our opinion that PNI is a mixed bacterial infection that despite its origin, clinical appearance and microbiologic findings, is highly uniform in terms of clinical course and treatment. Therapy is based on radical surgical debridement with excision of all necrotic tissue. The current plethora of terms seems impractical and confusing. We propose a rather comprehensive term perineal necrotizing infection for the sake of clarity. PMID- 2311426 TI - Chitosan: evaluation of a new hemostatic agent. AB - Topically applied chitosan fails to improve the control of bleeding in a liver laceration model when compared to pressure alone in both normal and heparinized rats, and both chitosan and pressure alone are significantly less effective in controlling bleeding than the application of thrombin. In addition, our histologic results suggest that there may be an increased inflammatory response by the healing liver following topical application of chitosan. PMID- 2311429 TI - The raised eyebrow. PMID- 2311428 TI - Leukopenia reduces microvascular clearance of macromolecules in ischemia reperfusion injury. PMID- 2311430 TI - Chronic lip edema with particular reference to the Melkersson-Rosenthal syndrome (MRS). PMID- 2311431 TI - Dermatology days. PMID- 2311432 TI - Cutaneous cryptococcosis simulating Kaposi's sarcoma in the acquired immunodeficiency syndrome. AB - A forty-one-year-old homosexual man with acquired immunodeficiency syndrome (AIDS) and biopsy proven Kaposi's sarcoma of the oral cavity presented to our clinic with a several month history of violaceous papules and plaques on his trunk and extremities. Although the patient already carried a clinical diagnosis of Kaposi's sarcoma, several biopsies of skin lesions were performed. Tissue specimens demonstrated cutaneous infection with Cryptococcus neoformans. As patients with AIDS have an increased incidence of both Kaposi's sarcoma and opportunistic infections, all progressing lesions should be biopsied in order to avoid missing a treatable life-threatening disease. PMID- 2311433 TI - Exogenous ochronosis in a Mexican-American woman. AB - Exogenous ochronosis resulting from the topical application of hydroquinone containing bleaching creams has been reported to occur almost exclusively in black subjects, and only after use of high concentrations of hydroquinone (greater than 3 percent) for many years. A Mexican-American patient is described who experienced exogenous ochronosis after using 2 percent hydroquinone cream for less than six months. PMID- 2311434 TI - Proliferating trichilemmal cysts over the vulva. AB - A sixty-year-old woman with multiple proliferating trichilemmal cysts over the vulva is described. The appearance of the eruptions suggests a hamartomatous origin. The lesions in the later stages resembled basal cell carcinoma. The malignant potential of the cysts and their treatment are discussed. PMID- 2311435 TI - Temporary hair removal in patients with hirsutism: a clinical study. AB - Women with facial hirsutism are burdened with hairs that often interfere with personal and work activities. Temporary hair removal is a major component in the management of hirsute patients. From a caseload of 1,000 patients, we submitted questionnaires to 271 and interviewed 135. We found that shaving was the most helpful and most frequently used temporary method. Judicious plucking can be helpful if tolerated, but care must be taken to avoid folliculitis, pigmentation, and scarring. Waxing and depilatories were used by less than 6 percent of patients on the face and by about 20 percent on other parts of the body. The avoidance of irritants and the use of hydrocortisone 1 percent cream are important in the management of any irritation due to hair removal techniques. Cosmetic coverups may be helpful. PMID- 2311436 TI - Subfertility in relation to welding. A case referent study among male welders. AB - A recent report indicates that welding work is associated with increased risk of reduced semen quality. The purpose of this study was to investigate a possible association between welding exposure and male subfertility. A cross-sectional population of 673 metal workers and electricians employed at six major Danish work places in the same geographic area constituted the study population. Data on reproductive and occupational experience was obtained by means of a self administered postal questionnaire. The response rate was 79 percent among welders and 83 percent among the other workers. A significantly increased rate of delayed conception in relation to welding work at the time of this event was observed when self-reported welding exposure among cases of delayed conception was compared to welding exposure both among age-matched referents and among referents with a child born without delay in conception. However, in the first approach the risk dropped to insignificant levels when adjustments were made for potential confounding factors. This preliminary study has methodological drawbacks, and the association between welding exposure and male fertility should be investigated further. PMID- 2311437 TI - Risk factors in continuous ambulatory peritoneal dialysis. A seven year follow up. AB - The purpose of the present study is to assess the mortality rate and the magnitude of technical problems forcing a patient off CAPD and to clarify the effect to which age, sex, diabetes, or cardiac disease influence mortality rate and technique survival. For this purpose, we used estimated survival probabilities by Kaplan-Meier methods. The study of all patients in our department dialysed on CAPD until July 1986 revealed a two-year survival of 63% for 121 patients. Mortality was significantly higher in patients with diabetes or prior cardiac disease. Non-diabetic patients over 60 had the same mortality rate as younger non-diabetic patients. The overall rate of transfer to other forms of dialysis was 35% after two years with little variation between subgroups, suggesting that parameters such as age, sex, diabetes and cardiac disease need not influence the choice of CAPD if based on technical considerations. PMID- 2311438 TI - A comparison of systolic time intervals measured by impedance cardiography and carotid pulse tracing. AB - The purpose of this study was to compare the systolic time intervals (STI) obtained by impedance cardiography and by the conventional carotid technique. This comparison was done with respect to: 1) correlations between variables obtained by the two methods, 2) ability to reflect drug-induced changes, 3) reliability in terms of reproducibility and 4) heart rate dependency of the variables measured. The study included 25 unmedicated patients with ischaemic heart disease and 36 healthy subjects. We obtained significant correlations between STI-variables measured by the two methods (p less than 0.001) and found that left ventricular ejection times were longer when determined by the carotid technique (p less than 0.01). We found a significant correlation between drug induced changes in STI-variables measured by the two methods (p less than 0.001). Both methods had a high degree of reproducibility and this parameter was significantly better within the same day, when impedance cardiography was used (p less than 0.01). The error due to the reading of STI-tracings obtained by impedance cardiography was very small when performed by the same observer. We found the pre-ejection period to be independent upon heart rate, while the left ventricular ejection time depended upon this parameter. We conclude that impedance cardiography and carotid technique differ with respect to the measurement of left ventricular ejection times, but not with respect to the measurement of other STI-variables. We furthermore conclude that both methods are reliable, but we recommend the use of impedance cardiography because it is easier to apply, it may be more precise and it can be used for simultaneous measurements of other haemodynamic variables. PMID- 2311439 TI - Pharmacokinetics and cerebrospinal fluid (CSF) concentrations of vancomycin in pediatric patients undergoing CSF shunt placement. AB - Staphylococcus epidermidis has been established as the common pathogen causing cerebrospinal fluid shunt infections. In addition, clinical isolates of S. epidermidis from infected shunts are typically resistant to methicillin. Vancomycin is often used for neurosurgical prophylaxis due to its excellent in vitro activity against methicillin-resistant staphylococci. Limited data are available about the pharmacokinetics and cerebrospinal fluid concentrations of vancomycin in pediatric patients intraoperatively. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations of vancomycin. Eight patients (mean age 8.3 +/- 7.0 years) received three doses of intravenous vancomycin, 15 mg/kg every 6 h. The first dose was administered 1 h prior to surgery. Blood samples were collected at 0, 0.5, 1, 2, 4, and 5 h after the end of the infusion. A cerebrospinal fluid sample was collected at the time of shunt insertion. Urine samples were collected over a 24-hour period. Vancomycin was measured with a fluorescence polarization immunoassay. The peak serum concentrations ranged from 15.6 to 33.7 micrograms/ml; cerebrospinal fluid concentrations ranged from less than 0.6 to 0.8 microgram/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.11 +/- 0.05 l/h/kg, 0.07 +/- 0.02 l/h/kg, 0.54 +/- 0.15 l/kg, and 4.8 +/- 4.0 h, respectively. Approximately 70% of total vancomycin dose was excreted in the urine. A 2- to 5-fold variation in total clearance and a 2.5-fold variability in renal clearance were observed. Low cerebrospinal fluid concentrations of vancomycin were present at the time of shunt insertion in these pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311440 TI - Heterogeneity of beta-lactamase production in Pseudomonas maltophilia, a nosocomial pathogen. AB - Twenty Pseudomonas maltophilia isolates were examined for susceptibility to beta lactam antibiotics, including carbapenems, and for beta-lactamase production. All the isolates were resistant to imipenem (MICs 64-512 mg/l) and to a lesser extent, to meropenem (MICs 16-256 mg/l). None of the isolates produced significant amounts of beta-lactamase without induction. Among the beta-lactams studied imipenem proved to be the most potent inducer; meropenem was a weaker inducer. Interestingly, 6-amino-penicillanic acid, even in concentrations up to 100 mg/l, entirely lacked induction activity. In any case enzyme production was drug concentration dependent and transient. Isoelectric focusing revealed 6 different enzymes distinguished by their different isoelectric points (pH 6.2, 8.3, 8.5, 9.0, 9.2 and 9.4). This suggested the lack of a unique beta-lactamase profile in P. maltophilia. Addition of 5 mM cyclic AMP (cAMP) or 0.5 mM cAMP-N6, O2-dioctanoyl (a lipophilic derivative) resulted in a marked drop of beta lactamase induction by imipenem as compared to the control assay. Monitoring of carbapenem hydrolysis by cell-free supernatants revealed inactivation of both carbapenems. Meropenem was inactivated about 5 times more rapidly than imipenem. Our studies revealed that beta-lactamase production in P. maltophilia as well as growth kinetics were influenced to a considerable extent by the nutrient medium employed. PMID- 2311441 TI - Comparative in vitro bactericidal activity of 24 antimicrobial drugs against Clostridium perfringens. AB - Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 log10 units within 2-4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (greater than or equal to 99.9% reduction of viable counts at 4-22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringens. PMID- 2311442 TI - In vitro synergistic activity of 5-fluorouracil with low-dose ozone against a chemoresistant tumor cell line and fresh human tumor cells. AB - We followed the concept that the chemical reactivity of ozone depends upon its oxidative properties. Activated oxygen species are causally involved in toxicity of certain chemotherapeutic drugs. We have tested this prediction in human cell cultures either to overcome chemoresistance and/or to increase chemical cytotoxicity. Our results indicate that ozone in combination with 5-fluorouracil (5-FU) makes a 5-FU-resistant cell line susceptible for the combined treatment modality. Furthermore, ozone acts synergistically or at least additive to chemotherapy in different tumor cell suspensions, derived from the breast and the colon. PMID- 2311443 TI - Comparative ototoxicity of ribostamycin, dactimicin, dibekacin, kanamycin, amikacin, tobramycin, gentamicin, sisomicin and netilmicin in the inner ear of guinea pigs. AB - Nine aminoglycoside antibiotics, ribostamycin (RSM), dactimicin (DAC), dibekacin (DKB), kanamycin (KM), amikacin (AMK), netilmicin (NTL), tobramycin (TOB), gentamicin (GM) and sisomicin (SISO) were administered intramuscularly to guinea pigs for 4 weeks, and ototoxicity and drug concentration in the inner ear fluid were determined. RSM and DAC showed the weakest ototoxicity against the cochlea and vestibular organs. AMK and KM were more toxic to cochlea than vestibular organs. DKB, TOM, GM and SISO were equally toxic to vestibular organs and cochlea. NTL was more toxic to vestibular organs than cochlea. As judged from the pinna reflex response and hair cell damage in the cochlea, the order of auditory toxicity was the following: SISO greater than GM greater than TOB greater than AMK greater than DKB greater than KM greater than NTL, DAC RSM, whereas the vestibular toxicity was in the following order: SISO greater than GM greater than DKB greater than TOB greater than NTL greater than AMK greater than KM greater than DAC, RSM. RSM, causing the weakest ototoxicity, showed a low drug concentration in the inner ear fluid, while GM, causing severe ototoxicity, showed the highest drug level under the same conditions. PMID- 2311444 TI - Transintestinal elimination of ciprofloxacin. AB - This study elucidates the routes of elimination of ciprofloxacin and its metabolites in two groups of 5 subjects each, one of healthy volunteers, the other of patients with severe renal failure having a creatinine clearance of 12 ml/min (range 8-16 ml/min). Each subject received one dose of 200 mg ciprofloxacin infused intravenously over 30 min. In an effort to recover the total dose administered, all urine and faeces were collected for the 7 days following dosing. Blood was collected at set intervals after dosing. Serum, urine, and faeces were assayed by high-pressure liquid chromatography for ciprofloxacin and metabolites. The ciprofloxacin serum half-life in healthy volunteers was 3.9 +/- 0.4 h and in patients with marked renal failure 11.2 +/- 2.5 h. The total amount of ciprofloxacin recovered in urine fell by a multiple of 3.4 from 65.3 +/- 10.7% in healthy subjects to 19.0 +/- 15.9% in patients with renal failure, and the metabolites from 12.2 +/- 2.3% in the former group to 5.8 +/- 5.1% in the latter. In contrast, the amount of ciprofloxacin eliminated in faeces increased, by a similar factor, from 11.4 +/- 2.6% in healthy subjects to 37.2 +/- 12.5% in patients with renal failure. The amount of metabolites in faeces increased analogously from 7.3 +/- 1.6 to 26.2 +/- 6.5%. Since ciprofloxacin was administered intravenously and biliary elimination of the drug and its metabolites is negligible, we propose that elimination by faeces is due primarily to transintestinal elimination. This study demonstrates that transintestinal elimination of ciprofloxacin serves as an extrarenal safety factor compensating for reduced elimination by the renal route. PMID- 2311445 TI - Interaction of beta-lactam antibiotics on bilirubin-albumin complex: comparison by three methods, total bilirubin, unbound bilirubin and erythrocyte-bound bilirubin. AB - The effects of 'third-generation' cephalosporins and penicillin analogues on the concentrations of total unconjugated bilirubin, unbound bilirubin and erythrocyte bound bilirubin were determined in blood samples. This study was performed, in vitro, at two bilirubin/albumin molar ratios and at various concentrations of antibiotics. The most effective displacers, considering the three methods, were antibiotics tightly bound to albumin: ceftriaxone and cefotetan. Cefoperazone, which is bound to albumin as tightly as these two antibiotics, caused no significant increase in unbound bilirubin but should be considered as a displacer drug on the basis of the variations of erythrocyte-bound bilirubin and total bilirubin. We suggest that drug interaction on bilirubin-albumin binding be investigated by several methods. PMID- 2311446 TI - Pharmacokinetics and cerebrospinal fluid concentration of nafcillin in pediatric patients undergoing cerebrospinal fluid shunt placement. AB - Postoperative infection is among the most common complications in patients with cerebrospinal fluid shunt placement. Nafcillin is often used for prophylaxis but not pharmacokinetic data are available perioperatively in pediatric patients. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal concentrations of nafcillin. Ten patients (mean age 8.0 +/- 5.6 years) received three doses of intravenous nafcillin, 50 mg/kg every 6 h; the first dose was administered 1 h prior to surgery. Multiple blood samples were collected during and after surgery and the cerebrospinal fluid sample was obtained at the time of shunt insertion. Urine samples were collected for 24 h after initiation of nafcillin. Nafcillin was analyzed with an HLPC method. The peak serum concentrations ranged from 22 to 107 micrograms/ml; cerebrospinal fluid concentrations ranged from 0.02 to 0.30 (mean 0.16 +/- 0.11) micrograms/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.90 +/- 0.55 l/kg/h, 0.12 +/- 0.04 l/kg/h, 0.70 +/- 0.52 l/kg, and 0.5 +/- 0.1 h, respectively. 16% of total nafcillin dose was excreted in the urine. A 4-fold variability in total clearance and a 10-fold variation in cerebrospinal fluid concentrations of nafcillin was observed in these patients. Further, the concentrations of nafcillin attained in the cerebrospinal do not appear to be adequate, based on its minimum inhibitory concentration of 0.5 micrograms/ml against very susceptible staphylococci. These data, in addition to the fact that an increasing number of staphylococci are becoming resistant to nafcillin, question the usefulness of prophylactic nafcillin in pediatric patients undergoing shunt procedures. PMID- 2311447 TI - Outcome study of protective services: comparison of interviews and records as data sources. AB - This study explores a complex area for research, and yields, despite the problems, distinct indicators for fruitful further research. PMID- 2311448 TI - [Legal requirements of continuing education and control]. PMID- 2311449 TI - [Emergency interventions in gastroduodenal ulcer]. PMID- 2311450 TI - [Use of fibrin glue in prevention and therapy of intra-abdominal adhesions]. AB - In prevention of the recurrent intestinal obstruction we performed at the Department of Pediatric Surgery of the University of Mannheim a sutureless plication of the small bowel with fibrin glue only over the last 7-year period. The postoperative course was uncomplicated in all patients. The clinical and experimental experiences suggest that the high concentrated human fibrinogen is able to start healing of the lesions of the serosa to prevent intraabdominal adhesions prospectively. Furthermore the time saving and easy procedure is to be stressed. First of all the high risk of tissue necrosis or intestinal perforation due to ischemia by sutures and stitches like in the traditional technique of plication is not present. PMID- 2311451 TI - [Experiences with a subcutaneous, fully resorbable bridge in construction a double loop ileo- and colostomy]. AB - Our experience with the subcutaneous absorbable bridge for constructing a temporary loop ileostomy and loop colostomy is described. The use of this subcutaneous absorbable bridge in 15 patients - 6 with loop ileostomy and 9 with loop colostomy - was almost without complications. The absorbable bridge is a progress for maturation of the stoma and for immediate postoperative as prospective fitting of a watertight appliance. The actual trend substituting the temporary loop colostomy by the loop ileostomy may be advanced by the unlimited use of the subcutaneous absorbable bridge for constructing a temporary loop ileostomy. PMID- 2311452 TI - [Discontinuity resection of the colon. Indications and results]. AB - In 83 patients discontinuity resection of the colon was performed. Due to negative selection factors postoperative mortality was 26.5%. In 37 patients continuity of the colon was restored, no patient died postoperatively. The only severe complication was formation of a colovesical fistula requiring a pull through operation. PMID- 2311453 TI - [Abscess excision and primary fistulectomy as initial therapy of peri-proctal abscess. A prospective analysis of 122 patients]. AB - A prospective study of 122 patients with anorectal abscesses was carried out to elucidate the value of abscess drainage with primary fistulectomy, when fistulas were identified. Patients were followed from 2 1/2 to 3 1/2 years with a mean follow-up of three years. In 52 patients (Group A) a primary fistula was present (42.6%), in 47 patients simultaneous excision of abscess and drainage of the intersphincteric space combined with partial sphincterotomy was performed. Recidives occurred in 17.3%. In 5 patients with a high transsphincteric or suprasphincteric fistula, a two-stage fistulectomy was done. In all 70 patients of group B no fistula was found at drainage operation. The incidence of recurrent anorectal abscess was 21.4%. In this group it is shown that the rate of recurrence was not related to a simultaneous excision of abscess and drainage of the intersphincteric space. PMID- 2311454 TI - [Protein C deficiency with recurrent infarct of the small intestine]. AB - Protein C and antithrombin III represent main inhibitors of the plasmatic coagulation system. Due to the lack of practicable assays the clinical importance of protein C was only established during the last six years. In familial protein C deficiency 77% of patients present with recurrent venous thromboses, half of them below the age of 30. In addition to recurrent superficial thrombophlebitis more serious manifestations like deep vein thrombosis and pulmonary embolism have been described. Mesenteric vein thrombosis has been reported in only 5 cases all of which could be controlled by conservative treatment. In our patient protein C deficiency was discovered 10 years after the angiographic diagnosis of portal and mesenteric vein thrombosis. Thereafter, the patient complained of recurrent abdominal discomfort. Intestinal ischaemia due to mesenteric vein thrombosis required segmental resection twice. Postoperatively the patient was heparinized. After excluding a secondary protein C deficiency due to a lack in vitamin K, hepatic disease, or disseminated intravascular coagulation, long-term anticoagulation by dicumarol was implemented as therapy of first choice. PMID- 2311455 TI - [Bronchial sleeve resection at the level of the segmental bronchus for benign bronchial adenoma]. PMID- 2311456 TI - [Sympathetic paraganglioma. A rare, retroperitoneal tumor]. PMID- 2311457 TI - [Sarcoidosis of the hand]. PMID- 2311458 TI - [Comment on the contribution by K. Jaeger: Axillary lymph node excision in breast cancer. Chirurg (1989) 60: 153]. PMID- 2311459 TI - Surgical management of anal condylomata in the HIV-positive patient. AB - A retrospective review of 677 patients who tested positive for the human immunodeficiency virus, evaluated from January 1986 to February 1988, demonstrated 119 patients (18 percent) with anal condylomata. Demographics of these patients were similar to the total human immunodeficiency virus group; ages ranged from 19 to 86 years (mean, 25 years). Ninety-four percent of patients were men, 62 percent were white, 30 percent were black, and 10 percent were other races, primarily Hispanic. Ten percent of the patients admitted to homosexual activity and 2 percent admitted to intravenous drug abuse. Sixty percent of the population had another sexually transmitted illness. The majority of patients were in early Walter Reed Classes (Stage I or II). With follow-up of 4 to 26 months (mean = 12 months), the recurrence rate for anal condylomata was 26 percent after local treatment with podophyllin and 4 percent after fulguration and excision. There were no operative complications. Our study confirmed that anal condylomata and sexually transmitted diseases are common in patients who test positive for the human immunodeficiency virus and that patients who test positive for the human immunodeficiency virus with early Walter Reed stages can be expected to do well with appropriate therapy. PMID- 2311460 TI - Long-term follow-up of patients with continent ileostomies. AB - Thirty-six patients were evaluated after having continent ileostomies for 16 to 20 years. Follow-up included clinical examination, response to a questionnaire, blood tests, and radiologic studies of the gallbladder. In addition, reservoir biopsies from 15 patients were examined. The patients were in excellent general health, all but one having gained weight postoperatively. There was no increased risk for gallstone formation or for urinary tract stone development. Although 11 of the 36 patients had reservoirs that were not provided with a valve, 92 percent of all patients were continent. Working capacity was normal in most patients and no harmful effects of the reservoir were revealed by morphologic or biochemical studies. In conclusion, no deleterious long-term effects were found as a result of the continent ileostomy. PMID- 2311461 TI - The influence of dairy and nondairy calcium on subsite large-bowel cancer risk. AB - This prospective study assesses the impact of fat and calcium intake on the risk of developing cancer in each large-bowel subsite. The study population is a cohort of Hawaii Japanese men who experience high rates of colon cancer, especially of the sigmoid segment. Total calcium intake is not related to the risk of colon cancer, and separation of calcium into dairy and nondairy sources does not alter the result. There is, however, a significant, monotonic increase in sigmoid colon cancer risk with decreasing total calcium intake. Similar trends are shown for both dairy and nondairy calcium. Dietary calcium is not consumed in large quantities among the Hawaii Japanese, partly because of their limited consumption of milk due to lactose intolerance. If calcium plays a protective role against sigmoid colon cancer, this effect is unlikely to be related to fat intake. Sigmoid colon cancer subjects had lower intakes of fat than other cohort men, and a statistical test for the interaction effect of total calcium and fat intake on colon cancer risk was statistically insignificant (P = 0.2). PMID- 2311462 TI - Long-term results of ileorectal anastomosis in ulcerative colitis in Stockholm County. AB - The long-term results of ileorectal anastomosis in patients with ulcerative colitis in Stockholm County over a 30-year period, 1955 to 1984, were investigated. During this time, 486 patients underwent colectomy and ileorectal anastomosis was performed in 60 of those patients (12 percent). A retrospective histologic examination of the slides of the operative specimens in the latter group revealed that nine patients had Crohn's disease. Of the 51 remaining patients with ulcerative colitis, the colectomy and ileorectal anastomosis was performed as an elective procedure in 44 cases (86 percent) and as a one-stage procedure in 48 patients (94 percent). Complications occurred in 7 of 43 patients (16 percent) undergoing an elective, one-stage procedure. There were two postoperative deaths (4 percent). There were 22 patients (43 percent) who had their ileorectal anastomosis in function at the time of follow-up, with a mean time of observation of 13 years. The cumulative probability of having the ileorectal anastomosis in function at 10 years was 51 percent. The causes of total excision were recurrent inflammation in the retained rectum (N = 23), dysplasia (N = 3), and postoperative complications (N = 3). No rectal carcinoma occurred. Patients with preoperative mild rectal disease had a better outcome (ileorectal anastomosis in function at time of follow-up) compared with patients with moderate rectal disease (P less than 0.001). The functional outcome of ileorectal anastomosis was, if anything, better than what is stated in the literature following pelvic pouch procedure. PMID- 2311463 TI - A comparison of simultaneous longitudinal and radial recordings of anal canal pressures. AB - A new anal manometry perfusion catheter is described that offers the capability of simultaneous linear longitudinal pressure measurements. The authors studied 20 control subjects with this catheter and with a four-quadrant perfusion catheter. An asymmetry of basal, squeeze, and relaxation pressures was found. The highest basal pressures were in the middle of the anal canal, regardless of quadrant orientation. Using the radial perfusion catheter, the squeeze pressure profile was consistent with a double-loop external sphincter mechanism. Using the linear perfusion catheter, the internal sphincter relaxation pressures show a greater negative deflection at the proximal portions of the sphincter, which was not achieved at points distally in the same quadrant. This implies that during reflex relaxation, pressure is maintained in the distal anal canal so that patients remain continent during sensory sampling of rectal contents. The authors believe this is the first time this same-quadrant longitudinal asymmetry of relaxation has been shown with a single rectal balloon stimulus. PMID- 2311464 TI - Disorders of impaired fecal control. A clinical and manometric study. AB - Two hundred eight patients with retention disorders have been studied. Most frequent causes were idiopathic (107), iatrogenic (57), and obstetric (33). Twenty-five patients experienced soiling, 31 had insufficient function, and 152 complained of incontinence. Seventy percent of patients with idiopathic incontinence did not experience urge, compared with 38 percent with iatrogenic and only 3 percent with obstetric incontinence. The incidence of prolapse was 58 percent in patients with idiopathic incontinence, 20 percent in patients with iatrogenic incontinence, and only 3 percent in patients with obstetric incontinence. The authors conclude that the function of the puborectalis sling is to create the anorectal angle to evoke the feeling of urge and to support intra abdominal contents and, furthermore, that fecal incontinence after anorectal surgery was likely caused by denervation. Anal resting and squeeze pressures varied widely. There was a huge overlap in the different groups. Mean resting and squeeze pressures were 9.5 kPa and 9.4 kPa, respectively, in controls, 4.8 kPa and 10.3 kPa, respectively, in the soiling group, 7.1 and 6.1 kPa, respectively, in the insufficient group, and 5.1 and 2.7 kPa, respectively, in the incontinent group. An incontinent external sphincter function could be defined as a function of the external sphincter causing a pressure increase of 5 kPa or less during straining. The ability to retain feces, therefore, is based on external sphincter function. Anal manometry is, indeed, a suitable technique to determine anal sphincter functions, but the presence of a retention disorder cannot definitely be determined. Its clinical application remains under discussion. PMID- 2311465 TI - Management of inguinal lymph node metastases from adenocarcinoma of the rectum. AB - Forty patients with inguinal lymph node metastases from rectal adenocarcinoma were reviewed. Patients were divided into three groups based on the extent of their disease: (1) patients with unresectable primary tumors; (2) patients with recurrent disease after abdominoperineal resection; and (3) patients with isolated inguinal lymph node metastases after abdominoperineal resection. Patients in Groups 1 and 2 underwent biopsy of their nodal metastases. Patients in Group 3 were treated by inguinal node dissection. Survival data were examined for each group, and four clinical and pathologic features were analyzed to determine their impact on prognosis: depth of invasion of the primary tumor (T1-2 vs. T3-4), number of positive lymph nodes in the rectal specimen (0-2 vs. greater than 2), extent of the inguinal lymph node metastases (unilateral vs. bilateral), and timing of the inguinal lymph node metastases (less than 1 vs. greater than 1 year after abdominoperineal resection). There were no five-year survivors in any group. Median survival was highest in those with isolated lymph node metastases, with 2 patients remaining free of disease, and was lowest in those with unresectable primary disease (7 months). Median survival was increased when inguinal LNM were unilateral (17 vs. 6 months; P less than 0.01) and when they occurred more than 1 year after abdominoperineal resection (21 vs. 7 months; P = 0.02). Stage of the primary lesion (depth of invasion and number of positive lymph nodes) did not affect survival. Of the 32 patients who underwent biopsy alone, only 1 developed a tumor-related groin complication. For patients with isolated inguinal lymph node metastases, inguinal node dissection is recommended for the purposes of local control and possible cure. For patients with extranodal disease, prophylactic excision of inguinal lymph node metastases is not warranted. PMID- 2311466 TI - Anastomotic healing after resection of left-colon stenosis: effect on collagen metabolism and anastomotic strength. An experimental study in the rat. AB - Anastomotic breaking strength and collagen metabolism in the colonic wall were studied after resection of a standardized left-colon stenosis in the rat. An increased complication rate was found in the stenosis group compared with the control group (27 percent vs. 2 percent) and the complications arise soon after surgery. The collagen turnover in the anastomotic area, as well as the changes of breaking strength, were equal between the groups in the early healing course, implying that the stenosis group, as an entity, did not show impairment in the studied parameters predisposing for complications. Other factors such as mechanical strain by the increased fecal bulk and increased bacterial load may contribute to occurrence of the anastomotic complications. PMID- 2311467 TI - Experience with the biofragmentable anastomotic ring (BAR) in bowel preoperatively irradiated with 6000 rad. AB - Previous studies from the authors' laboratory using the biodegradable anastomotic ring (BAR) have demonstrated the safety of this device in animals irradiated preoperatively with the equivalent of 5000 rad; sutured, stapled, and BAR anastomoses all had leak rates of 10 percent or less in this setting. This study was undertaken to assess the safety of the BAR after irradiation with the equivalent of 6000 rad. Thirteen mongrel dogs underwent preoperative irradiation to the rectum and rectosigmoid, receiving 6000 rad according to the nominal standard dose equation. After a three-week rest period, each dog underwent anterior resection of the rectosigmoid and anastomosis with the BAR. The anastomoses were evaluated for early and late healing and anastomotic leaks. The results were compared with previous data from the authors' laboratory using an identical model. Radiographic leaks were found in 7 of 10 sutured anastomoses, 8 of 10 stapled anastomoses, and 3 of 13 BAR anastomoses (P less than 0.01). Comparative clinical leaks were 5 of 10 for sutured, 5 of 10 for stapled, and 3 of 13 for BAR anastomoses. These data suggest that the BAR may offer added safety to an anastomosis after preoperative irradiation. Whether this effect is due to the atraumatic technique of placing the device, improved blood flow to the anastomotic margins, or other factors, is still underdetermined. PMID- 2311468 TI - Inflammatory bowel disease--spectrum. PMID- 2311469 TI - Intraoperative cleansing of the impacted colon using an endotracheal tube. AB - A simple technique for intraoperative cleansing of the impacted colon is described. Saline-irrigation through the torn balloon of the endotracheal tube (38 French) and massaging the impacted feces facilitated drainage of the obstructed colon. This technique was done in two emergent colon operations and immediate anastomosis could be performed safely. An endotracheal tube is always available in an operating room, so this technique is useful and effective in an emergent colon operation without special preparation. PMID- 2311470 TI - An adapter for stapling of a colorectal anastomosis. AB - A technique involving the use of an end-to-end anastomosing stapler for low anterior resection has been modified to allow for a low colorectal anastomosis with an anus-pushing rubber adapter. The facility and safety of this procedure, under direct vision, has been confirmed. PMID- 2311471 TI - Effectiveness of a long intestinal tube in a one-stage operation for obstructing carcinoma of the left colon. AB - Five consecutive patients with obstructing carcinoma of the left colon were successfully managed by long intestinal tube decompression. The tube was introduced pernasal into the duodenum on the day of admission. The tube advanced spontaneously into the ascending colon with marked abdominal decompression within several days. Thereafter, preoperative colonic irrigation through this tube was performed. In three of five patients, segmental colectomy was accomplished without intraoperative cleansing. In two patients, fecal residue was removed by intraoperative colonic irrigation using the long tube. Proximal colostomy was avoided in all patients. This treatment protocol enabled: 1) both preoperative and intraoperative colonic irrigation and cleansing; 2) elective surgery instead of emergency; 3) safe one-stage operation with secure colonic anastomosis; and 4) segmental resection rather than subtotal resection of the colon. PMID- 2311472 TI - A surgical treatment of thrombosed external hemorrhoids. AB - An anatomically based method for the surgical treatment of thrombosed external hemorrhoids has been described. It involves a circumferential incision over the thrombosed hemorrhoidal sinus and removes the thrombi from involved veins. PMID- 2311473 TI - Colonoscopy in patients with a primary family history of colon cancer. PMID- 2311474 TI - ASCRS Research Foundation comes of age. PMID- 2311475 TI - Effects of prostaglandins and indomethacin on cerebral blood flow and cerebral oxygen consumption of conscious newborn piglets. AB - The effects of the prostaglandins (PG) PGE1, PGE2, PGF2 alpha and PGI2, and of indomethacin on cerebral blood flow (CBF) and cerebral metabolic rate for O2 (CMRO2) were studied in 60 1- to 3-day-old conscious piglets. Effects of PGs in indomethacin-treated animals were also measured. CBF was measured by radiolabelled microspheres prior to and 45 s after intracarotid bolus injections of 0.1-10 micrograms/kg PGE1 and 0.01-1 micrograms/kg PGE2, PGF2 alpha and PGI2. PGE1 decreased CBF by 30% at the dose of 0.1 micrograms/kg and increased it by 39.5% (n = 6) at the higher dose of 10 micrograms/kg. PGE2 (n = 6) increased CBF at all doses administered. PGF2 alpha (0.01 micrograms/kg, n = 8), which is a potent cerebral vasoconstrictor in adults, and PGI2 (0.1 micrograms/kg, n = 6) significantly increased CBF in newborn piglets (p less than 0.05). CMRO2 correlated with CBF in all groups of animals, except for those injected with PGI2. Indomethacin (3 mg/kg i.v.) decreased CBF by 39% (p less than 0.01, n = 6). This effect was partially reversed by PGI2, but not by PGE1 and PGF2 alpha. Sagittal venous blood and arterial-sagittal venous blood differences in concentrations of PGF2 alpha, but not of PGE and 6-keto-PGF1 alpha, correlated weakly but positively (r = 0.4, p less than 0.05) with CBF in indomethacin treated piglets. These data indicate that PGs exert significant effects on cerebral circulation in the newborn. Primary PGs are principally cerebral vasodilators and are devoid of vasoconstrictive effects in the newborn, except for PGE1 which produces vasoconstriction at low dose (0.1 micrograms/kg). Thus, we speculate that a relative deficiency in cerebral vasoconstrictor effect of PGs may contribute to the reduced upper limit of the CBF autoregulatory range of the newborn. PMID- 2311476 TI - The effects of indomethacin on renal function and intracranial hemorrhage in infants with patent ductus arteriosus. AB - The effects of indomethacin on patent ductus arteriosus (PDA) were retrospectively studied by evaluating 1,600 consecutive infants less than 36 weeks gestation from 1983 to 1986. Two hundred thirteen infants were diagnosed with a PDA, and 102 infants received indomethacin. Indomethacin was associated with successful PDA closure in 81 infants (79%), with 59 infants (58%) closing after a single dose. No cases of renal failure were observed after indomethacin. Nine infants were treated despite a creatinine (Cr) value greater than or equal to 1.5 mg/dl. Cr improved in all these infants after therapy. Blood urea nitrogen values were greater than or equal to 30 mg/dl in 22 infants at the time of treatment; 18 infants (82%) improved. An intracranial hemorrhage (ICH) was detected in 23 infants (22%) by cranial ultrasound prior to indomethacin; there was no progression after treatment. Data suggest that indomethacin is highly associated with closure of a PDA, and therapy did not result in prolonged renal dysfunction or worsening ICH. PMID- 2311477 TI - Age-related differences in the use of morphine, diazepam, and pancuronium for mechanically ventilated children. AB - Mechanically ventilated children usually require a combination of sedation (morphine = M, diazepam = D) and paralysis (pancuronium = P) to minimize anxiety, discomfort, and the risks of self-extubation, tracheal injury, and pulmonary barotrauma. We sought to determine whether our use of MDP varied with patient age. Cases where the dosage of MDP would be influenced by neurological, hemodynamic, or painful diagnoses were excluded. The 36 cases selected were divided according to age into three groups (less than 4 months = A, 4-18 months = B, greater than 18 months = C). The daily sum of MDP dosages was calculated for each of the 326 study days, a mean of 9 study days for each case. The median daily drug usage in group B (2.3 mg/kg/day) was twice that in either group A (younger) or group C (older) (both p less than 0.001). This finding may be explained by developmental changes in physiology, pharmacology, and behavior, and may have been influenced by a paradoxical drug effect or multiple drug antagonism. PMID- 2311478 TI - Pharmacokinetics of cefotaxime in preterm infants. AB - Pharmacokinetic parameters of cefotaxime (CTX) and its metabolite desacetylcefotaxime (DCTX) were assessed on the 3rd day of treatment in 10 preterm infants (28-37 weeks gestation) aged 3-8 days and receiving 25 mg/kg CTX twice daily. Blood samples were collected from an umbilical artery catheter at 0, 0.08, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12 h after a short peripheral infusion (5 min) and were assayed by high-performance liquid chromatography. During the 12 h following the CTX infusion, serum concentrations of CTX remained above the mean bactericidal concentration for pathogens commonly isolated during the neonatal period. The mean (+/- SD) elimination half-life, volume of distribution, total body clearance and area under the serum concentration-time curve (AUC0-12 h) for CTX were: 3.68 +/- 1.48 h (range: 1.89-6.82), 431 +/- 149 ml/kg (219-636), 1.57 +/- 0.80 ml/kg/min (0.60-3.27) and 373 +/- 206 micrograms/ml/h (170-867), respectively. The AUC0-12 h for DCTX was 170 +/- 93 micrograms/ml/h (61-374). A significant inverse relationship was found between gestational age and the elimination half-life of CTX, and the AUC of both CTX and DCTX. PMID- 2311479 TI - Dicloxacillin absorption and elimination in children. AB - We determined the apparent bioavailability of dicloxacillin in 26 children between the ages of 0.24 and 143 months by comparing the area under the serum concentration versus time curve following intravenous and oral administration of 25 mg/kg. With intravenous infusion the overall mean half-life of elimination was 0.53 +/- 0.20 h, the AUC was 70.15 +/- 32.18 mg.min/l and the apparent volume of distribution was 0.29 +/- 0.09 l/kg. The overall average bioavailability was 59.89%. Children less than 6 months old had a shorter time to peak concentration (1.39 +/- 0.49 h) and the lowest oral bioavailability (64.35 +/- 13.62%) in comparison to children more than 60 months old. In children older than 60 months the time to peak was 1.79 +/- 1.16 h and the average oral bioavailability was 79.38 +/- 32.87%. However, children less than 6 months old had the least variability in absorption, the coefficient of variation (CV) of oral bioavailability was 13.62%, while in children between 6 and 40 months old the CV was 60.4%: children older than 60 months had the most variability in absorption, a CV of 32.87%. This variability was not dependent on the formulation administered. After 5 years of age the bioavailability increased with increasing age. PMID- 2311480 TI - Intralipid-induced decrease in oxygenation in neonates is related to changes in the respiratory quotient. AB - Intravenous lipid infusion has been previously reported to be associated with hypoxemia. Different mechanisms have been proposed, but none have explored the decrease in respiratory quotient (RQ) following lipid administration as a possible factor. Ten neonates without respiratory problems, breathing room air and on total parenteral nutrition were studied. Arterialized capillary blood gases, transcutaneous PO2 (TcPO2) measurements and expired gas concentrations were obtained, prior to and 1 g/kg of 10% lipid emulsion was infused over 6 h. Following lipid infusion, the TcPO2 decreased from 72 +/- 8 to 65 +/- 8 mm Hg and the RQ decreased from 0.94 +/- 0.08 to 0.86 +/- 0.5 (p less than 0.05), while the pH, PaCO2 and the alveolar-arterial oxygen tension difference did not change. The decrease in TcPO2 significantly correlated with the decrease in alveolar oxygen tension. Seven of the 10 infants had a significant decrease in TcPO2 with a significant decrease in RQ from 0.98 +/- 0.05 to 0.85 +/- 0.06 (p less than 0.01). In 3 patients with no significant change in TcPO2 following intralipid administration, the RQ was initially significantly lower than the rest of the group (0.85 +/- 0.04; p less than 0.05) and did not change at the end of the infusion (0.88 +/- 0.03). These data suggest that the changes in PaO2 following lipid infusion in neonates without lung disease and breathing room air, are related to the decrease in alveolar oxygen tension secondary to the change in RQ. PMID- 2311481 TI - Various levels of maternal caffeine ingestion during gestation affects biochemical parameters of fetal rat brain differently. AB - Pregnant dams were divided into four groups on day 10 of gestation. Dams of group 1 were fed an 20% protein diet as controls. Dams of groups 2, 3 and 4 were fed a 20% protein diet supplemented with 0.5 mg, 1 mg and 2 mg caffeine/100 g body weight of dams, respectively. Pups were delivered surgically on day 22, and their brains were rapidly removed and analyzed for DNA, protein, cholesterol, zinc and alkaline phosphatase activity. The dams' brains were analyzed for the same parameters as those of the pups. Plasma and brain caffeine levels were also determined in caffeine-supplemented groups. The pups' brains in group 2 were heavier than those in group 4. The DNA concentration of group 2 was higher than that of the other groups. The protein concentration of group 4 was higher than that of the other groups. The cholesterol concentration of group 3 and 4 was less than that of the controls. The zinc concentration of group 4 was less than that of group 2. Alkaline phosphatase activity was decreased in groups 3 and 4 compared with either controls or group 2. Dams showed no significant difference among the groups in the same biochemical parameters except for cholesterol concentration that was higher in groups 2, 3 and 4 than in the controls. Plasma and brain caffeine levels of the fetuses and plasma caffeine of the dams in group 4 were higher than those of either group 2 or 3. It is concluded that various amounts of maternal caffeine intake exert different effects on fetal brain growth. In contrast, the effect of caffeine on the dams' brain is relatively minor. PMID- 2311483 TI - Proceedings of the 15th Japanese Society of Developmental Pharmacology and Therapeutics. October 29-30, 1988, Tokyo. Abstracts. PMID- 2311482 TI - Sulphotransferase and its substrate: adenosine-3'-phosphate-5'-phosphosulphate in human fetal liver and placenta. AB - The activity of sulphotransferase (ST) towards 2-naphthol and the concentration of its endogenous substrate adenosine-3'-phosphate-5'-phosphosulphate (PAPS) were measured in human fetal and adult liver and in the placenta. The activity of ST (mean +/- SD; nmol/min/mg protein) was 0.28 +/- 0.06 (fetal liver); 1.82 +/- 0.44 (adult liver; p less than 0.001) and 0.021 +/- 0.014 (placenta; p less than 0.001). The concentration of PAPS (mean +/- SD; nmol/g wet tissue) was 10.1 +/- 0.9 (fetal liver); 23.4 +/- 2.4 (adult liver; p less than 0.001) and 3.6 +/- 1.1 (placenta; p less than 0.001). Both ST and PAPS were higher in fetal liver than in placenta. The difference between fetal liver and placenta was more marked for ST than for its substrate. Such a consideration was also drawn when fetal and adult liver were compared. Thus, the activity of the ST rather than the concentration of its substrate seems to be the limiting factor in sulphation. PMID- 2311484 TI - Assessing physiological changes from hyperbaric therapy. AB - This article, the first of two on hyperbaric oxygen therapy (HBOT) describes the detailed nursing assessment required for these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311485 TI - Creativity in critical care nursing. PMID- 2311486 TI - Critical care voices: intuition in nursing practice. PMID- 2311487 TI - Music therapy results for ICU patients. AB - The following investigation studied the physiological and emotional responses to taped music programs of patients in coronary and surgical Intensive Care Units (ICU). Previous studies have investigated physiological or psychological impact individually, but rarely explored the effects simultaneously. The results of this study support music therapy as a nursing intervention which supports the holistic care of the critically ill patient. PMID- 2311488 TI - Circular questions: a family interviewing strategy. AB - Assessment strategies for working with the family of the critically ill typically focus on collecting data from family members in order to determine if the family requires further support or intervention. This article describes using the technique of circular questioning to obtain information from and provide the family with new information. Circular questions are interventions as well as assessment strategies. The authors provide critical care examples of the use of circular questions with families of the critically ill. PMID- 2311489 TI - An educational program for a comprehensive pulmonary care unit. AB - The opening of a pulmonary cluster unit designed to provide care for patients from the critical phase of their illness through their recovery created a need for an educational program to develop the expertise of the nursing staff. The author describes how to develop a program to increase the expertise of staff nurses in caring for pulmonary patients through all phases of their illness. PMID- 2311490 TI - Thirst: a critical care nursing challenge. AB - Thirst is a symptom commonly experienced by critically ill patients. Critical care nurses have the opportunity to prevent and reduce thirst by recognizing the types of thirst, identifying patients at risk, monitoring physiological parameters, and providing comfort measures. PMID- 2311491 TI - Do patients understand what they read? PMID- 2311493 TI - Introduction to health insurance and reimbursement issues: getting reimbursed. PMID- 2311492 TI - Use of educational resources in diabetes patient education. PMID- 2311494 TI - The diabetes pictorial scale: a direct measure of young children's knowledge, attitudes, and behavior relevant to their insulin-dependent diabetes mellitus. PMID- 2311495 TI - Nutrition education: taking it one step at a time. AB - Although it is important for most patients with diabetes to gain a broad background in nutrition information and exchange principles, for many these will be long-range goals. Don't be in such a hurry to teach so much that you lose the patient's interest and end up confusing the patient with too much knowledge and information. Keep the principles of adult learning in mind as you set your goals for initial, intermediate, and advanced learning objectives for each patient. And, finally, consider evaluating the DNIS as a useful addition to your patient education resources for initial level teaching tools. PMID- 2311496 TI - Factors that influence diabetes patient teaching performed by hospital staff nurses. AB - Hospital staff nurses are frequently expected to teach patients and families with diabetes. A study was conducted to answer the questions: (1) According to nurses' perceptions, what factors influence conducting diabetes education? (2) Do staff nurses have sufficient knowledge to teach diabetes management principles? Thirty nine staff nurses from adult units of a university hospital completed an investigator-designed survey and a Diabetes Knowledge Test (DKT). Eleven nurses attending a workshop on diabetes patient management were pre- and posttested to determine the workshop's effect on perceptions and knowledge. Perceived factors that interfered with teaching included lack of time, inadequate teaching skills, lack of patient interest in learning, and absence of a physician's order for teaching. The workshop had little influence on perceptions but significantly increased the mean DKT score from 70% to 78% (P = .03). The findings suggest that expecting all staff nurses to adequately educate patients in diabetes management may not be realistic. PMID- 2311497 TI - Role of the diabetes nurse educator in improving patient education. AB - Hospitalized patients learn from staff nurses as well as from specialized diabetes nurse educators. This paper examines the involvement of staff nurses in diabetes patient education and the useful roles of the specialist, particularly as change agent and consultant. It focuses on how the diabetes nurse educator bridges the knowledge gap between the expertise of the specialist and practices of the staff nurse in providing patient education for self-care. PMID- 2311498 TI - The Rowdy Reactors: maintaining a support group for teenagers with diabetes. AB - A successful support group for teenagers with type I diabetes requires more than informational lectures and discussions. Active learning by doing and the client's feeling of being in control are important. Attempts at gaining control require development of self-image, group solidarity, and the ability to communicate with nondiabetic peers and parents. Here is how one group did it. PMID- 2311499 TI - The health belief model: evaluation of a diabetes scale. AB - Scales that make theoretical concepts of health beliefs operational must be shown to have acceptable levels of reliability and validity before they can be incorporated into teaching programs. This paper describes the process used to evaluate a Health Belief Model scale. A revised 11-item scale is proposed for use by diabetes educators. Content validity of the initial scale (76 items) and the shorter version was verified. Reliability estimates obtained by factor structure provided evidence of measurement accuracy for the proposed 11-item scale. Analyses of construct and criterion validity provided additional support to suggest the use of the HBM11 scale for clinical practice. PMID- 2311500 TI - Sugar and fat substitutes: the challenge for today and tomorrow. AB - Companies have contributed greatly to meeting the challenge of providing a variety of reduced calorie ingredients allowing food manufacturers to choose the most appropriate ingredient to prepare the tastiest product. These sugar and fat substitutes alone do not lead to healthier eating. The diabetes educator needs to teach clients who wish to lose weight, or to reduce sugar or fat intake, to select foods made with sugar or fat substitutes (when available) as part of a balanced meal plan that meets their nutritional requirements. These products can be a factor in achieving the balance of diet and exercise essential to a healthy life-style. PMID- 2311501 TI - The relationship between a couple's marital adjustment and beliefs about diabetes mellitus. AB - Twenty married couples with one partner diagnosed as having diabetes at age 40 or older within the past 5 years participated in this study. Participants completed the diabetes or family version of Beliefs About Diabetes (BAD) and the Dyadic Adjustment Scale (DAS). Results showed that perceived barriers to diet and to medication by the person with diabetes were associated with higher marital satisfaction and quality of marriage. In contrast, for the nondiabetic spouse, the perceived benefits of diet were negatively associated with the ability to work with the diabetic spouse. Additional research is needed to better understand the effect of diabetes on the marital relationship. PMID- 2311502 TI - Legal aspects of the team approach to diabetes treatment. AB - Expansion of the team approach to diabetes care will most likely have significant ramifications in malpractice liability law as applied to diabetes educators, physicians, treatment teams, and supporting hospitals. This analysis focuses on the nature of the team approach to diabetes care, nationally promulgated standards for its practice, and predictions of the parameters of malpractice law. The establishment of a national certification procedure identifies specialists in diabetes education, allowing for the expanded roles of diabetes educators, and promotes a minimum standard of care to which practitioners may be held. Likewise, the criteria for recognition by the American Diabetes Association (ADA) serve as guidelines for diabetes education programs. Current legal decisions suggest that these standards may be applied nationally as measures of malpractice liability. Application of certification guidelines may minimize allegations of malpractice. PMID- 2311503 TI - Words and meaning: a cautionary tale for diabetes educators. AB - The authors developed a Diabetes Attitude Survey (DAS) to measure the attitudes of health care professionals toward diabetes. After examining the results of an initial survey using the DAS, the authors felt that it would be useful to know something about the attitudes of patients regarding these same diabetes-related issues. The DAS was reworded to eliminate technical terms and to make it appropriate for patients with diabetes. To assess the impact of these wording changes, both versions of the DAS were sent to a sample of physicians, nurses, and dietitians. The wording changes produced changes in scores on the majority of the items that had been modified. The paper discusses some of the reasons for the changed scores and the impact of modifying the wording of assessment and evaluation instruments. PMID- 2311504 TI - Diabetic diet compliance: student dietitians reverse roles. AB - Eleven student dietitians attempted to comply with a calorie-controlled, diabetic diet for 1 week. Pre- and posttest questionnaires, as well as food diaries, were used to assess projected versus actual compliance, obstacles to adherence, and thoughts and feelings about following a prescribed medical regimen. Scores of deviation from the meal plan and food exchanges were calculated to describe dietary compliance. Only one student indicated she was able to adhere to the diet for the entire week. Twenty-seven percent of the students complied with their meal plan 90% of the time. All students felt they would be more empathetic in their relationships with patients and involve patients to a greater extent in planning their diets. PMID- 2311505 TI - Diet counseling in a multicultural society. AB - Successful diet counseling is dependent on culturally sensitive communication strategies. Health care practitioners can improve cross-cultured counseling through a four-step process. First, they must become familiar with their own cultural heritages. Second, they must become acquainted with the cultural background of each client. Third, through an in-depth cross-cultural interview, they must establish the client's cultural background, food habit adaptations made in the United States, and personal preferences. Fourth, they must modify diets based on unbiased analysis of the dietary data. The best chance for compliance occurs when diets are modified with consideration for client's cultural and personal preferences. PMID- 2311506 TI - The cookie curriculum. PMID- 2311507 TI - Professional development. Editorial opinion. PMID- 2311508 TI - Financing the care of diabetes mellitus in the 1990s. PMID- 2311509 TI - Vulnerable subjects in clinical studies. PMID- 2311510 TI - [Bone alkaline phosphatase as an activity parameter of acromegaly]. AB - Serum levels of growth hormone (GH: arithmetic mean of three measurements eight hours apart), somatomedin C (SmC), alkaline phosphatase activity and the bone isoenzyme of alkaline phosphatase (as the liver/bone isoenzyme ratio) were measured in 26 patients with acromegaly (11 men and 15 women; mean age 45.5 [24 66] years), 18 in the active and eight in the nonactive phase of the disease. Activity was characterized by a raised (660 [330-1149] ng/ml), inactivity by a normal (186 [40-300] ng/ml) SmC concentration. All 18 patients with active acromegaly had an abnormally low liver/bone isoenzyme ratio (mean of 0.66 [0.01 1.28]). In seven of the eight patients with inactive acromegaly it was within normal limits. Thus measurement of bone alkaline phosphatase, which is significantly cheaper than that of SmC, is suitable for assessing activity. PMID- 2311511 TI - [13C-urea breath test as a non-invasive method for the detection of Helicobacter (Campylobacter) pylori]. AB - The 13C-urea breath test was used for diagnosing noninvasively the possible presence of Helicobacter (formerly called Campylobacter) pylori in 20 patients with dyspepsia (ten men and ten women, mean age 40.2 [24-74] years). H. pylori was cultured from 14 patients, while in six the culture was negative. The proportion of 13C in expired air was measured by isotope mass-spectrometer and expressed as Delta (basal value about 20%). A dose of 2.5 mg urea per kg body weight (BW) was ingested after a standard meal. The test was repeated with 1.75 and 1.0 mg/kg BW in five subjects. Delta had increased significantly after 30 min in all H. pylori-positive patients (P less than 0.001). The maximal value after 90 min ranged from 38 to 114%; in the H. pylori-negative patients it was 24%. After 1.75 and 1.0 mg/kg urea the maximal value after 90 min was 39-52% and 30 52%, respectively. Using a dose of 2.5 or 1.75 mg/kg BW tagged urea one can reliably distinguish between presence and absence of H. pylori. It is sufficient to test a basal and a 90-min expired-air sample. PMID- 2311512 TI - [Acute isolated ischemia of the right ventricle with ST elevation in V1 to V4]. AB - An acute anteroseptal infarction was diagnosed in a 51-year-old man whose ECG showed ST elevations in leads V1-V4 after acute retrosternal pain for about 20 min. Angiography revealed proximal occlusion of the right coronary artery, while the dominant left coronary artery was fully patent. After successful recanalization of the right coronary artery with intracoronary infusion of urokinase, the ST elevations quickly disappeared and impending right-heart infarction was avoided. Isolated right-heart infarction can imitate the ECG pattern of anteroseptal infarct and should be considered if the height of ST elevations diminishes from V1 to V4. PMID- 2311513 TI - [Oxygen multi-stage therapy]. PMID- 2311514 TI - [Malaria on the Turkish Riviera]. PMID- 2311515 TI - [Pancreatic function tests]. PMID- 2311516 TI - [The physician and AIDS: how do patients react?]. PMID- 2311517 TI - [Effect of body posture and venous congestion on blood fat picture]. AB - The effects on the concentrations of total cholesterol, high-density lipids (HDL), triglycerides and glycerol of temporary venous occlusion during blood sampling and changing body posture (lying and standing) were measured on 20 healthy male volunteers (mean age 25 [21-27] years) with normal blood-lipid levels. Venous occlusion in the upper arm increased the concentration of lipids in the antecubital vein, by 8% after five min and 37% after 15 min. Initial levels were restored 10 and 15 min after the occlusion. Blood-lipid levels were similarly raised on standing up again. After 5 min they had risen by about 9%, after 15 min by 16%. After renewed recumbency the levels were up from the initial values by 5% after 10 min and by 3% after 15 min (P less than 0.01). The concentration of free glycerol on the whole varied randomly, but there was a statistically significant rise after 10 and 15 min standing. These results indicate that different techniques of blood sampling can influence the lipid concentrations in venous blood. PMID- 2311518 TI - [Morphology and clinical picture of thymus carcinoid]. AB - A large mediastinal tumour was discovered radiologically in a 50-year-old man, with at times blood-tinged sputum and dyspnoea. Parasternal needle biopsy revealed a thymic carcinoid. After surgical excision of the tumour, which had argyrophilic foci (total weight of tumour 1,605 g), histochemical analysis demonstrated neuron-specific enolase, synaptophysin and chromogranin, as well as calcitonin (as the only hormone). For the first time in a thymic carcinoid, radioimmunoassay demonstrated growth-hormone-releasing hormone (2 micrograms/g tumour tissue). Post-operative radiotherapy (total dosage 50.5 Gy) was instituted because histological examination had shown invasion of the capsule and blood vessels. There has been no local recurrence or metastases after three years. PMID- 2311520 TI - [Intra-aortic balloon pumping in poisoning-induced left-heart failure?]. PMID- 2311519 TI - [Metastatic basal cell carcinoma]. AB - One day before his death, a 66-year-old man who had been suffering since childhood from a severely itching and repeatedly bleeding skin lesion was examined for the first time by a general practitioner who immediately advised hospitalization. On admission, an extensive rodent ulcer on his back was noted and septic shock diagnosed. Because of the hopeless diagnosis no life-supporting measures were undertaken. Postmortem examination revealed an 18 x 26 cm sized ulcerating basal cell carcinoma on the back with infiltration of the thoracic vertebrae and a fist-sized paravertebral abscess between the left upper and lower lobe of the lung and abscessing pneumonia. Two metastases each were found in the right lung and in both kidneys with the histologically characteristic picture of basal cell carcinoma. This case confirms the observation that this type of carcinoma has the potential for metastasizing, but it usually does not do so because of its biological characteristics and early curative excision. PMID- 2311521 TI - [Diagnosis and therapy of constipation]. PMID- 2311522 TI - [Cesium-137 content in children 1 and 3 years after Chernobyl]. PMID- 2311523 TI - [The effect of housing on the development of calluses and subcutaneous mucus cysts on the limbs of swine]. AB - Extremities of pigs often show swelling of various size and consistency. The aim of the present investigation was to determine the cause of the swelling with special emphasis on housing conditions. A total of 168 animals kept on slatted and/or partly slatted floors and 55 pigs kept on straw were examined. The swelling was partially caused by connective tissue proliferation only, but more often consisted of non inflamed subcutaneous bursae. Skeletal changes near the periost could never be seen. In pigs kept on straw weals and subcutaneous bursae practically never developed, whereas in animals kept on concrete, these changes did occur more frequently and were more pronounced with time. PMID- 2311524 TI - [Microbial changes as the cause of failures of the therapy of bacterial diseases of the urogenital organs of swine]. AB - In long-term clinical and bacteriological controlled breeding sows of 15 stocks with a high rate of urinary tract infections in 41 sows (= 8.97%) of 457 chronic infected sows a spontaneous change of the causative microorganism was seen. In clinical trials to test the effectiveness of new chemotherapeutics in sows suffering from urogenital infections changes of bacteria were noticed during and after therapy. In selected cases the proceeding of change using a quinoxaline-di N-oxide-derivative and an aminoglycoside-antibiotic is demonstrated. After parenteral application of the quinoxaline-di-N-oxide-derivative in 3 of 6 cases a change of the causative agent happened. Treating the sows with the aminoglycoside antibiotic there was a change in 18.2% of urinary tract infections and in 25.0% of genital tract infections. The causes of changes of the causative microorganisms are discussed and conclusions are drawn for diagnosis and therapy of urinary and genital tract infections in the sow. PMID- 2311525 TI - [The veterinarian and the law]. AB - A propaedeutic lesson in forensic medicine is given for Vets. PMID- 2311526 TI - [The least requirements for the rotation of swine for slaughter from loading to transport to resting time until stunning from the viewpoint of animal protection and meat quality]. AB - 1. According to the loading density there is a significant increase of the physical burden (strain) during a transport of pigs to the slaughterhouse. Keeping up minimal requirements (kgs pigs/sqm) the stress reaction decreases and the meat quality becomes better. 2. Each transport produces excitement which can be shown in higher respiratory and heart frequencies. The slaughtering of excited animals shows a higher percentage of carcasses with bad meat quality. Waiting times from at least 2 hours up to a maximum of 4 hours shows that the percentage of carcasses with a better meat quality increases. 3. Handling of animals at the slaughterhouse prior to stunning by dividing the number of pigs into small groups of at least 9 animals is very important especially because it reduces the excitement of the pigs prior to stunning. The stunning results are getting better. Mistakes in handling pigs prior to stunning especially in guiding them to the stunning place usually destroy all positive efforts for optimal transparent conditions and keeping up waiting times after transport. 4. The last step ahead to the stunning equipment. No good solution does exist which makes the pigs willingly do this last step and enter the place where the stunning is performed. This results in the CO2 stunning system itself as well as in the automatic electrical stunning equipment using a restrainer. 5. Stunning with CO2. PMID- 2311527 TI - [Eperythrozoon infection in swine: effect on the acid-base balance and the glucose, lactate and pyruvate content of venous blood]. AB - The influence of latent and of splenectomy-induced clinically manifest Eperythrozoon suis infection on the following parameters of the carbohydrate metabolism and the acid-base status was tested in venous blood of German Landrace pigs: Levels of glucose, lactic and pyruvic acid, blood-pH, base excess, actual bicarbonate concentration, standard bicarbonate concentration, pCO2, pO2. The latent E. suis infection resulted in a consistent decrease of blood glucose level. 23 days after infection, blood glucose was reduced by 25% of the initial value. The other parameters were not changed by latent E. suis infection. Acute Eperythrozoonosis induced severe hypoglycaemia (means Gluc, = 39.7 mg/dl and blood acidosis (means pH = 7.13). In vitro experiments showed that break-down of glucose in E. suis infected blood occurs very rapidly. There was no significant reduction of the glucose concentration in control blood that had been treated accordingly. There was an increase of lactic acid (means = 62.7 mg/dl), pyruvic acid (means = 1.86 mg/dl), and pCO2 (means = 82.1 mm Hg). The concentrations of actual bicarbonate (means = 24.8 mmol/l) and standard bicarbonate (means = 20.9 mmol/l) were lowered, and there was a negative base excess (means = -3.56 mmol/l). The ratio of lactic and pyruvic acid changed from 11:1 to 30:1. It seems likely that E. suis itself is able to metabolize glucose. Acidosis is considered to result from both the increase of lactic acid (metabolic component) and an impairment of pulmonary gas exchange (respiratory component). PMID- 2311529 TI - [Progression and control of leptospirosis in a sow herd]. AB - After a short review about etiology, epidemiology, clinical symptoms, diagnosis and therapy of leptospirosis the course and therapy of an acute leptospirosis outbreak in a breeding herd with nearly 240 sows is described. The microscopic agglutination test (MAT) served for diagnosis and was most reliable for estimation the actually stage of infection when used twice with an interval of several weeks. As causative agent serovar L. pomona was identified, whereby cross reactions were seen to serovars L. grippotyphosa, L. bratislava and L. copenhageni. Therapy of all animals with Terramycin/LA (Pfizer) at three times with intervals of five days and doses of 20 mg oxytetracycline/kg b.w. distinctly reduced the incidence of abortion and stillborn or mummified pigs. Local irritations, relative to the intramuscular administration of oxytetracycline, mostly were low-graded and temporary. For the next months acute infections could not be registered. Probably due to infections from leptospires-reservoirs, maintained by numerous existing mice and puddles on the pasture-ground, leptospirosis occurred again six months later. Only another antibiotic therapy of the whole herd and simultaneous eradication of rodents as well as closing the pasture led to a long-termed control of leptospirosis in this herd. PMID- 2311528 TI - [Secondary effects caused by feed medication in swine]. AB - Giving medical feed to weanling pigs it is possible to produce a vitamin K deficiency as a side effect, which is caused by destruction of the intestinal flora. In this investigation the effect of different drugs in a vitamin K deficient diet on blood coagulation of weanling pigs was examined. In a first trial clinical symptoms of a vitamin K-dependent coagulation disorder could be seen in five from six animals after feeding a combination of sulfadimidine, tylosin, furazolidone and arsanilic acid. Animals showed haemorrhages, when they were housed on flatdecks as well as on concrete floor. This indicated that coprophagy plays no role in pigs for supply of vitamin K. Feeding these drugs in other combinations or one of the drugs alone caused no clinical signs in a second trial. Significant differences to untreated control pigs were found only in one group (sulfadimidine/arsanilic acid) for activities of coagulation factors. Other groups demonstrated only prolongation of clotting times in single animals. Pigs, which received sulfadimidine within their ration, were more often affected than other animals. In a third trial suckling pigs were treated over a period of three weeks with a drug combination used in the first trial to allow an adaptation of the intestinal flora. Same treatment after weaning was unable to produce any clinical symptoms, but led to distinct coagulation disorders in pigs treated before as well as in untreated animals. It is supposed that the development of a vitamin K-deficiency depends on faecal bacterial count and on the specific resistance of intestinal flora in individuals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311530 TI - [Preliminary results of noncontact temperature measuring using an infrared thermometer on the tarsus pf swine with osteoarthrosis tarsi deformans]. AB - The surface temperature on tarsus of 54 performance tested boars of about 60 kg of Swedish Landrace was measured by means of infra-red thermometer at three measuring points (MP1, MP2 and MP3). MP1 was situated above the tuberculum of os metatarsale III or, as visualised in 21 slaughtered boars, above pathoanatomical alterations of osteoarthrosis tarsi deformans (OATD). MP2 was located directly medially and MP3 laterally from MP1. A clear palpatory symptom was found only with 10 boars, while all 21 slaughtered boars showed different morphological lesions of OATD. The average temperature at MP1 was 35.69 degrees C and was significantly higher (P = .01) than at MP2 (35.34) and MP3 (35.30). The temperature differences between MP1 and MP2 or MP3 were statistically reliable. Boars, who had a clear palpatory symptoms at tuberculum, showed an average temperature at MT1 of 36.27 degrees C, which was higher (P = .0114) than of those with an unclear palpatory symptom (35.64 degrees C). The results show that the temperature differences are the consequence of OATD. PMID- 2311531 TI - [A practical vein catheter for small ruminants (short report)]. PMID- 2311532 TI - [Comparison between dialysis methods and centrifugation/filtration for collecting fecal fluid from calves]. AB - Faecal samples of different consistency from 15 calves were subjected to two methods to separate faecal fluid. Osmolality as well as the concentrations of electrolytes and short chain fatty acids were determined for each of the fluid samples obtained and the results compared. For dialysis the following procedure was used: small dialysis bags filled with dextran 10% were placed in the cooled (4 degrees C) faecal sample to which gentamycin was added to inhibit fermentation. Equilibrium between dialysate and surrounding fluid was reached after 24 hours. However, depending on the consistency of the faeces, after 6 hours 90 to 95% of the final osmolality at 24 hours was reached. In regard to osmolality, sodium, potassium and chloride concentrations as well as to concentrations of short chain fatty acids no significant differences could be observed between the faecal fluid obtained by dialysis or by centrifugation (3500 g, 20 min, 4 degrees C) and subsequent filtration. Distinctly higher concentrations of calcium and inorganic phosphate were measured in the filtrates; the probable explanation is that these ions in faeces are largely present as poorly diffusible compounds (in particular with faeces of a more solid consistency) or bound to the cell membranes. PMID- 2311533 TI - [Metaphylaxis and therapy of the MMA syndrome of sows with Baytril]. AB - The efficiency of antibacterial metaphylaxis and therapy on the control of the MMA-syndrome has been investigated in a large breeding-herd with a total of 828 sows in the study. For this the recently developed quinolone-derivate Baytril was used. Feed medication with furazolidone and sulfadimidine reduced the incidence of disease to 29.7% (control 41.3%), injection of Baytril on the day of parturition reduced it to 10.8% (using a dosage of 1.25 mg/kg body weight) respectively 6.8% (dosage 5 mg/kg). Treatment also resulted in a lower incidence of elevated milk-pH (greater than 6.7). The development of piglets was good in all groups of metaphylaxis. Litters of sows which had been treated with Baytril as prophylaxis or therapy had no low extremes in the weight gains of the piglets. In the treatment of MMA-affected animals Baytril was significantly superior as compared to Trimethoprim-Sulfonamide, if a dosage of 5 mg/kg body weight was used. Using a dosage of 1.25 mg/kg body weight both drugs had the same effect. Even at the end of the five month of the study there was no isolation of bacteria resistant against Baytril. PMID- 2311534 TI - Development and properties of a cell culture produced vaccine for hog cholera based on the Chinese strain. AB - The Chinese strain of hog cholera virus (HCV) was adapted to suspension cultures of the established swine kidney cell line SK6. The strain designated "Cedipest", is produced on the basis of a seedlot system. The masterseed virus was identified in vitro and in vivo, and was found free from extraneous pig pathogenic viruses by repeated animal inoculation followed by appropriate serological tests. A distinct and reproducible relationship was ascertained between infectivity in vitro and protection. Pigs inoculated with 400-600 TCID50 of the Cedipest strain proved fully protected against challenge with greater than 100 pig LD50 of a virulent strain of HCV at 7 days and at 6 month post vaccination. PMID- 2311535 TI - A seroepidemiologic study of bovine respiratory syncytial virus (BRSV) in Turkey. AB - In this study, a survey of cattle for neutralizing antibodies to respiratory syncytial virus (RSV) in Turkey is presented. 490 serum samples were collected from several state farms and some private flocks in different regions of Turkey. The serologic examination was done by the microtiter serum-neutralization technique. In this report, a positive serum antibody titer at dilutions of 1:2 was demonstrated in 226 (46.12%) of the 490 sera tested. PMID- 2311536 TI - A case report: encephalitis in lions. Pathological and virological findings. AB - An acute outbreak of encephalomyelitis in lions from a safari-park was investigated. Three moribund lions were euthanatized and a post mortem examination was performed. A disseminated non-suppurative polioencephalomyelitis with demyelination in the spinal cord was the only pathological finding. From tonsil material of one lion feline herpesvirus type 1 was isolated. Canine distemper virus, pseudorabies virus, feline infectious peritonitis virus and rabies were excluded as cause of the disease. The possible role of FHV-1 in etiology of the disease is discussed. PMID- 2311537 TI - Detection of phocine distemper virus using the polymerase chain reaction. AB - During the fatal seal epizootics in the North and Baltic Seas in summer 1988 a virus was isolated which was shown to be the causal agent. It was subsequently classified as morbillivirus by neutralization assays, reaction with monoclonal antibodies and nucleic acid hybridization studies. The virus (tentatively called Phocine Distemper Virus, PDV) is difficult to grow in culture making rapid diagnosis difficult. We have used the Polymerase Chain Reaction (PCR) as an alternative and fast method to detect the presence of virus-specific nucleic acid and we describe here the amplification of cell culture derived PDV RNA in a "one tube" reaction using heterologous (Rinderpest Virus cDNA derived) F gene primers. The resulting 370 bp DNA fragment was shown to be morbillivirus derived by Southern blot hybridization using cloned RPV F gene as probe. PMID- 2311538 TI - Angiolymphoid hyperplasia with eosinophilia: an uncommon tumor of the external auditory canal. AB - We present a case of an 80-year-old woman with a six-month history of painless nodules in her external auditory canal. Biopsies of these nodules revealed ALHE. This type of lesion rarely has been reported in the otolaryngologic literature, despite the fact that the head and neck are sites of predilection. The potential of malignancy with this disorder is debatable, and the histologic features overlap with other benign and malignant vascular tumors. Thus, adequate local excision is recommended. PMID- 2311539 TI - Hypoglossia congenita. AB - Hypoglossia and aglossia are rare congenital malformations, especially when found as isolated abnormalities. In view of their usual association with other anomalies of the face, oral cavity, and distal extremities, an accurate investigation is required. We describe a 2-year-old girl with isolated hypoglossia and severe dental disease. Clinical understanding of the changes in the mechanisms of oral suction, mastication, swallowing, and speech, as well as the existing dental occlusion, requires a multidisciplinary team approach so that a more effective treatment can be administered. PMID- 2311540 TI - Primary liposarcoma of the pharynx. AB - We describe a rare case of primary pharyngeal liposarcoma in a 64-year-old man who had multiple recurrences. The available literature is reviewed and discussed. Although it is very difficult to assess the prognosis and treatment of pharyngeal liposarcomas, it appears that the histologic characteristics of the individual tumor and its location and resectability determine the outcome of treatment. However, because of its rare occurrence clinically, no single institution has been able to gain enough experience to formulate reliable long-term prognoses and therapeutic guidelines. PMID- 2311541 TI - Noma and noma neonatorum. AB - Noma and noma neonatorum are rare gangrenous diseases that result in mutilating loss of tissue in the oronasal region. Noma usually occurs in patients between the ages of 2 and 5 years who are malnourished, have suffered a precedent illness, or are in some way immunodeficient, or all of the above. The gangrenous slough is thought to be caused by a mixed infection of oral bacterial pathogens. The disease may be fatal when it occurs in a severely debilitated patient. Noma neonatorum produces somewhat similar appearing lesions in the neonate. The infectious organism is usually Pseudomonas and the disease is generally accompanied by a life-threatening pseudomonal sepsis. Both diseases are rare in North America. Patients with noma and noma neonatorum were treated at the Children's Hospital and Medical Center, Seattle, WA. We present these cases and a literature review. PMID- 2311542 TI - Polyvinylchloride tracheotomy tubes as foreign bodies in the tracheobronchial tree. PMID- 2311543 TI - Speech defects as an unusual complication of adenotonsillectomy. PMID- 2311544 TI - The prevalence and clinical significance of maxillary sinus mucous retention cysts in a general clinic population. AB - Previous studies have documented the occurrence and potential clinical significance of MSMR cysts. Studies also have alluded to a relationship between the MSMR cyst and certain signs or symptoms of disease. We determined the prevalence of MSMR cysts in a general clinic population and identified some important correlations with clinical signs and symptoms. PMID- 2311545 TI - Surgical anatomy of the guinea pig middle ear. PMID- 2311546 TI - An office treatment for snoring. PMID- 2311547 TI - The scars of newborn intensive care. AB - Many techniques used in neonatal intensive care are invasive and the risk of producing skin damage is high. To investigate this, 100 consecutive survivors of neonatal intensive care (gestation 26-42 weeks, median 32) were examined in detail by a single observer at 16-29 months of age, and the scar severity, site and likely cause noted. Scarring was present in all infants although it was usually trivial. The total number of scars was inversely related to gestational age and directly related to the duration of intensive care. Eleven children had cosmetically or functionally significant lesions caused by chest drain insertion, extravasation of intravenous fluid or skin stripping by adhesive tape. To reduce the frequency and severity of skin damage, neonatal staff need to be aware that many routine procedures may lead to long term scarring. In particular, more careful wound closure after chest drain removal is needed. PMID- 2311548 TI - The influence of postnatal respiratory adaptation on sodium handling in preterm neonates. AB - The relationship between sodium handling and alveolar-arterial oxygen gradient (AaDO2) was studied in 26 preterm babies requiring ventilation from birth. The difference between sodium intake and urinary sodium excretion was determined in sequential, four hourly periods throughout the course of the respiratory illness. Sodium retention changed from positive (mean 1.42 mmol kg-1 day-1) during the phase of deteriorating respiratory function to negative (mean - 1.99 mmol kg-1 day-1) during improving respiratory function. This difference is highly significant (P less than 0.001). A temporal relationship is also shown, in the form of individual time plots of AaDO2 and sodium retention for each baby; changes in sodium handling parallel changes in AaDO2. The diuresis that accompanies improving respiratory function is characterised as a natriuresis, with free water clearance remaining unchanged before and after the point of improvement. We suggest that a primary change in sodium handling, triggered by postnatal respiratory adaptation, may initiate the contraction in extracellular fluid volume that characterises early postnatal existence. PMID- 2311549 TI - Fetal breathing movements in pregnancies complicated by premature membrane rupture in the second trimester. AB - Forty pregnancies complicated by oligohydramnios in the second trimester due to prolonged and premature membrane rupture (PPROM) were followed prospectively to determine factors influencing fetal breathing activity and the relationship of fetal breathing movements (FBM) to outcome. The patients were retrospectively divided into three groups according to the presence or absence of FBM. Membrane rupture occurred at a significantly earlier gestation in those pregnancies in which FBM were absent. Duration of membrane rupture only differed significantly between pregnancies in which FBM were intermittent or consistently present. In the group in which FBM were always absent (N = 12) all the infants died in utero or in the neonatal period due to pulmonary hypoplasia. In the group with FBM always present (N = 17) all infants survived. In the third group FBM were observed in some, but not all, ultrasound examinations (N = 11). Some infants survived (N = 6), while others died either due to pulmonary hypoplasia or neonatal sepsis. These results show the necessity for several serial ultrasound examinations, all demonstrating the absence of fetal breathing movements, before pulmonary hypoplasia in PPROM can be predicted confidently. PMID- 2311550 TI - Relative abundance and molecular size of immunoreactive insulin-like growth factors I and II in human fetal tissues. AB - Previous studies which have quantitated tissue mRNA transcripts have suggested that IGF II is expressed in substantially greater amounts than IGF I during human fetal development. However, this has not been tested directly by recovery and quantitation of IGF peptides from fetal tissues. Tissues from human fetuses were extracted in 1 M acetic acid, and insulin-like growth factor (IGF) I and II immunoreactive species separated from the supernatants by acidic gel filtration. When total immunoreactive IGF I or II eluting from Sephadex G50 between approximately 6 and 15 kDa molecular weight was estimated, allowing for likely blood contamination, tissues from five fetuses contained, on average, 230 fM/mg cell DNA IGF I and 690 fM/mg IGF II. The ratio of IGF II: IGF I peptide content varied from 1.6 in muscle to 7.8 in thymus. Separation of tissue supernatants, fetal plasma and fetal fibroblast-conditioned culture medium on Sephadex G75 revealed that immunoreactive IGF II eluted with molecular weights between 8 and 15 kDa, in addition to 7.5 kDa. While fetal tissues contain more IGF II than IGF I immunoreactivity, the likely presence of IGF II peptide does not agree with the great excess of mRNA for IGF II reported previously. PMID- 2311551 TI - Effect of amnionitis on the complement system of preterm infants. AB - The development of the complement system was studied by quantitation of total hemolytic complement activity (CH50), C1q, C3, C4, and C3 split product (C3d) in cord plasma of nine human fetuses (17-22 weeks of gestation), 110 preterm (24-36 weeks of gestation) and 30 term neonates. The complement levels were analyzed in relation to various illnesses of preterm infants. Histological examination of the placenta revealed a higher incidence of amnionitis in the placenta of less than 34 gestational weeks. In cases without amnionitis, there were significant correlations between complement levels and gestational age. In cases with amnionitis, the complement system was activated even in infants of less than 28 weeks gestation. The complement levels correlated with the extent of the inflammation in the placentas and umbilical cords except for C1q. In infants with Wilson-Mikity syndrome, complement levels other than C1q were significantly elevated in comparison with those of infants with respiratory distress syndrome. In the group of preterm infants without amnionitis, no differences were found between infants with intrauterine growth retardation and those with growth appropriate for gestational age. PMID- 2311553 TI - The influence of growth retardation on perinatal hypoxic-ischemic brain damage. AB - The effect of growth retardation on the extent of brain damage produced by hypoxia-ischemia was assessed in immature rats. Newborn rats were raised in litters of 6 or 14 pups from day 2 to 7. On postnatal day 7, those immature rats raised in litters of 14 weighed 18% less than animals raised in litters of 6 (P less than 0.001). They then were subjected to cerebral hypoxia-ischemia by unilateral common carotid artery ligation followed by 3 h of exposure to 8% oxygen-92% nitrogen at 37 degrees C. Upon return to their dams, all litters were culled to 6 pups. At 30 days of age, the animals underwent perfusion-fixation of their brains under pentobarbital anesthesia. Brain damage was assessed by measuring the length and width of each cerebral hemisphere. The extent of brain damage varied from no difference in the size of the two cerebral hemispheres to marked shrinkage of the hemisphere ipsilateral to the common carotid artery occlusion. The range of brain damage between the well-nourished and poorly nourished animals was comparable. Rank order of the extent of damage demonstrated significantly greater tissue injury in those animals well nourished prior to hypoxia-ischemia (Mann-Whitney U-test; P = 0.003). The results indicate that nutritional deprivation in the immature rat is associated with a decreased rather than increased susceptibility to brain damage arising from hypoxia-ischemia. The findings of the investigation have relevance to the human infant suffering from intrauterine growth retardation (IUGR). PMID- 2311552 TI - Short-term effects of early suckling and touch of the nipple on maternal behaviour. AB - The objective was to evaluate the effects of suckling within 30 min after birth when skin-to-skin body contact for mothers and infants was held constant in both cases (n = 32) and control groups (n = 25). Mother-infant interaction during breast-feeding, infants' time spent in nursery and different aspects of breast feeding were evaluated. Prolactin and gastrin were measured in maternal serum before and after breast-feeding on day 4 post partum. The aim to evaluate effects of early post delivery suckling failed since only six of the 32 case infants did suck at this time. In spite of this, we found three significant differences among cases and controls. In the case group where all infants had touched or licked the areola and nipple, the mothers left the infants in the nursery for a significantly shorter time and significantly more mothers talked to their infants during the short breast-feeding observation. Median gastrin levels were significantly lower in cases than in controls both before (P less than 0.01) and after (P less than 0.03) breast-feeding. In conclusion, the infant's early touch of the mother's areola and nipple seemed to have positively influenced the mother/infant relationship during the first four days after birth. It was also associated with lower maternal gastrin levels which suggests that maternal neuroendocrine functions were also influenced. Ten months after birth, we found no differences between cases and controls. PMID- 2311554 TI - Type IV collagen in developing human lung: a comparison between normal and hypoplastic fetal lungs. AB - Human lung tissue obtained from 24 aborted fetuses of varying gestational ages (beyond 24 weeks) was examined for immunolocalisation of type IV collagen, using monoclonal antibody. Twelve cases of lung hypoplasia associated with oligohydramnios were compared with 12 normally developed lungs over the same gestational age range acting as control. Type IV collagen was located in alveolar septa and subepithelial basement membranes in all the lungs examined but showed less prominently in hypoplastic lungs than in control lungs of a similar gestational age. The findings suggest a potential role of type IV collagen in maturation of the developing human lung. PMID- 2311555 TI - The prediction of total body fatness in early infancy. AB - We have investigated the relationship between percentage fat mass and skinfold thicknesses in a group of male and female infants at 5, 11 and 26 weeks of age. Fat-free mass and hence fat mass was determined using an H2(18)O dilution technique. Multiple regression analysis was used in order to evaluate whether the triceps and subscapular skinfold measurements, in a number of models, could predict percentage body fat. In all cases skinfold thickness was poorly predictive of percentage body fat. We suggest that variation in the distribution of internal and external stores of body fat may be a major factor accounting for the poor predictive value of skinfold thickness in this study. PMID- 2311556 TI - Assessment of industrial sewage impacts by adenylate energy charge measurements in the bivalve Cerastoderma edule. AB - Laboratory toxicity tests performed on the bivalve Cerastoderma edule submitted to sublethal concentrations of paper mill effluent revealed significant decreases of adenylate energy charge (AEC), and changes in the total adenylate pool were observed in a 24-hr period even for the lowest concentration of pollutant tested. Field transfer experiments of C. edule from a safe zone to polluted areas of the Sado estuary were carried out at two different times of the year. Close proximity to sewage outfall was shown to result in significant decreases in AEC values within 24 hr. One week after transfer, either normal AEC values were found or the organisms died, depending on the location of the sampling station. PMID- 2311557 TI - The perfused fish gill preparation in studies of the bioavailability of chemicals. AB - The bioavailability of chemicals has received considerable attention in aquatic toxicology, and it is generally agreed that information about bioavailability is lacking in many situations. Here an experimental approach that can be used to assess the bioavailability of chemicals to fish is presented. The gills are the primary uptake site of dissolved chemicals in fish. A perfused gill preparation from rainbow trout is described. The preparation allows direct measurements of the absorption rates of chemicals across the gill epithelium. The use of the preparation in bioavailability studies is exemplified by a study of cadmium availability in different water qualities, by the pH-dependent absorption of hexavalent chromium and by a study on the pH-dependent absorption of halogenated phenols across the gills. PMID- 2311558 TI - Toxicity of the pyrethroid insecticide fenvalerate to a fresh water fish, Tilapia mossambica (Peters): changes in glycogen metabolism of muscle. AB - Toxic effects of a pyrethroid insecticide, fenvalerate, on fish muscle glycogen metabolism were investigated. Estimations were made after 10 and 20 days of exposure, and altered muscle glycogen metabolism was observed. The changes included a significant (P less than 0.001) decrease in the levels of glycogen, pyruvate, maleate dehydrogenase (MDH), succinate dehydrogenase (SDH), and phosphorylase a, b, and ab activities, while elevated levels of lactic acid, aldolase, and lactate dehydrogenase (LDH) activity were observed under fenvalerate intoxication. There was a decrease in opercular movement and oxygen consumption with an increase in concentration of fenvalerate. PMID- 2311559 TI - Sequential study of the pathology of Prudhoe Bay crude oil in chicken embryos. AB - Ten microliters of Prudhoe Bay crude oil was applied to the shell of fertile leghorn chicken eggs on Day 9 of incubation. Gross and microscopic pathological changes were examined in embryos surviving 1, 2, 4, and 9 days after treatment. Liver necrosis, renal lesions, and extensive edema appeared 2 days after treatment and reached maximal prevalence 4 days after treatment. There was minimal repair of the lesions from Day 4 to Day 9 after treatment. Pathological changes, including liver necrosis, mineralization in the kidney, infiltration by a large number of heterophils in the liver and spleen, subcutaneous edema with formation of large blisters, and reduction in body weight and length were still present on Day 18 of incubation, close to hatching time. PMID- 2311560 TI - The effects of salinity and temperature on the toxicity of copper to 1-day and 7 day-old larvae of Hediste (Nereis) diversicolor (O. F. Muller). AB - The effects of salinity and temperature on the toxicity of copper to 1-day and 7 day-old larvae of Hediste diversicolor were tested using factorial analysis. Mortality of larvae was influenced by salinity, temperature, and copper, but 1 day-old larvae were more susceptible than the 7-day-old larvae. Resistance to copper increased with age. Low concentrations of 5 and 20 micrograms/liter copper were more inhibitory to 1-day and 7-day old larvae, respectively, than were higher copper levels. The responses of 1-day-old larvae to copper levels from 0 to 20 micrograms/liter and 7-day-old to copper levels from 0 to 100 micrograms/liter copper were complex. Increasing salinity 7.6 to 30.5% reduced both copper toxicity and protozoa/bacteria attacks. PMID- 2311561 TI - Physiological effects in fish exposed to effluents from mills with six different bleaching processes. AB - Immature rainbow trout (Salmo gairdneri R.) were continuously exposed in a flow through system to a total of six different bleached kraft mill effluents (BKME) at two exposure concentrations (400 and 2000 times dilution) for 7 weeks, during three consecutive years (1982-1984). The fish were exposed in outdoor tanks connected to the outgoing water from a parallel mesocosms study simulating the Baltic littoral (Fucus vesiculosus) zone. After exposure, hematological, osmoregulational) and mixed function oxidase (MFO) parameters were studied. The results showed that conventional choline bleaching (C95 + D5)EHDED, with and without treatment in aerated lagoons, had the strongest effects on the fish exposed. Oxygen prebleaching followed by high (50%) substitution of the active chlorine as chlorine dioxide, as well as oxygen prebleaching and normal (85%) chlorine levels in the CD step and treatment in aerated lagoons, had the fewest effects on the fish. The results imply a complex pattern of effects where the relative prevalence of MFO-stimulating and -inhibiting substances may give different biological results in fish exposed to these kinds of effluents. PMID- 2311562 TI - Physiological responses of Vicia faba plants to sulfur dioxide. AB - Exposure of broad bean (Victa faba L.) plants to 270 +/- 32 and 670 +/- 45 micrograms m 3SO2 for 1.5 hr daily between 40 and 85 days of their ages resulted in an increase in their transpiration rate, water saturation deficit, phenol content, and peroxidase activity and a decrease in protein content. With the increase in number of exposures of plants to SO2, chlorotic and brown, necrotic visible injury signs were also developed in leaves. It was further noted that the magnitude of undesirable biochemical changes, which possibly helped in the formation of new pigment characteristic of necrotic tissue of SO2-exposed plants, was not totally dependent on the pollutant concentration. PMID- 2311563 TI - Estimation of releases into rivers with the steady-state surface water model EXWAT using dichloromethane. AB - The surface water model EXWAT is applied to monitoring studies of hazardous substances to estimate site-specific emissions from measured concentrations. The model includes the main processes which govern the fate of chemicals in rivers, namely, advection, volatility, degradation processes, sedimentation, resuspension, and protonic equilibria. The steady-state solution of the linear mass balance equations leads to proportionality between input and concentration of a chemical, which is used to assess input rates from measured concentrations. Subsequently, the model can be used for pollution control and identification of unknown releases. With measured concentrations in the Rhine near Koblenz (95 km downstream from the mouth of the river Main) the load of dichloromethane from the tributary Main was estimated. The comparison with measured concentrations in the tributary mouth has a good agreement in this case. PMID- 2311564 TI - Aluminum accumulation in a lotic mayfly at low pH--a laboratory study. AB - The authors experimentally studied the occurrence of aluminum (Al) accumulation in nymphs of the mayfly Heptagenia sulphurea at low pH (4.5). Nymphs were exposed to two Al concentrations (0.2 and 2 mg inorganic Al liter-1), and two exposure times (2 and 4 weeks), the longer time period also including a molting phase. The major part of the Al was deposited on/in the exuviae of the nymphs, as Al determination in nymphs showed a 70% decrease in Al content after molting. When nymphs were exposed for two instar periods, with a molt in between. Al content almost doubled (2.34 mg Al g-1 dry wt) compared with that of a one-instar treatment (1.24 mg Al g-1 dry wt). This indicated that Al also accumulated within the mayfly nymphs. Determination of Al in emerged adults confirmed that most of the metal was deposited externally on the nymphs. No clear indications of Al accumulation were found in this short-term experiment. The implications for food web accumulation of Al are that internally accumulated Al may be transferred to terrestrial predators by mayflies and other aquatic insects that leave their final exuvium in the water. However, aquatic insects that make their final molt in the terrestrial environment, and thereby bring adsorbed Al out of the water are more likely vectors. PMID- 2311565 TI - Ionic imbalances in the CNS of neonate rat during induced benthiocarb stress. AB - The effect of benthiocarb, an organocarbamate herbicide, on the ionic profiles of the developing central nervous system of rat has been studied. The ionic profiles altered by benthiocarb toxicity indicate possible perturbations in the electric activity of neurons, in oxygen consumption, and in the ATPase system, as well as disruption in the movement of ions across ionic pumps and impairment of synaptic transmission. PMID- 2311566 TI - In vivo effect of the organophosphorus insecticide trichlorphon on the immune response of carp (Cyprinus carpio). I. Effect of contamination on antibody production in relation to residue level in organs. AB - The organophosphorus insecticide trichlorphon was tested at medium (10 and 20 ppm) and high concentrations (20,000 ppm) on antibody production against Yersinia ruckeri vaccine. No statistically significant effect was observed on humoral response or on hematocrit. Contamination of organs was analyzed by acetylcholinesterase activity. At 20,000 ppm only liver and brain were highly contaminated; spleen and lymphocytes were not significantly contaminated. At 20 ppm no residue was found in organs. PMID- 2311568 TI - Electromyographic analysis of reach in individuals with cerebral palsy. AB - Electromyographic analysis in both the time domain (root mean square EMG) and the frequency domain (mean power frequency EMG) of the biceps, triceps, wrist extensors and wrist flexors were analysed in six young cerebral palsied adults and six normal individuals. The subjects sat in a Rifton positioning chair. Each subject's right arm was positioned with the shoulder adducted, the elbow at 90 degrees and the hand resting on the arm rest. The subject then reached the right arm forward to grasp a dowel which was placed at shoulder level in front of the subject. There was no significant difference between the time it took the two groups to do the required movement. The RMS analysis indicated the muscle activation was variable among subjects, with evidence of concontraction of the antagonist muscles for the disabled group. The frequency analysis indicated that the disabled group had significantly lower mean power for the biceps and the wrist extensor muscles compared to the normal group. Neurological differences or fibre type abnormalities may account for these differences. PMID- 2311567 TI - In vivo effect of the organophosphorus insecticide trichlorphon on immune response of carp (Cyprinus carpio). II. Effect of high doses of trichlorphon on nonspecific immune response. AB - The effect of trichlorphon, one of the most widely used organophosphorus insecticides, on the nonspecific immune response in carp (Cyprinus carpio) was studied. The effect of 20,000 ppm trichlorphon on the immune response was followed for 3 and 56 days after intoxication. The effect of 10,000 ppm trichlorphon on the nonspecific immune response of carp experimentally infected by Pseudomonas alcaligenes and Aeromonas punctata was also examined. Leucocyte number, phagocytic ability of neutrophils, percentage NBT-positive PMN cells, phagocytic index, lysozyme level in serum, and ceruloplasmin activity in plasma were examined on Days 2, 4, 6, 8, 10, 14, 18, 22, and 26 after carp were exposed. After intoxication leukopenia was observed as decreases in phagocytic ability of neutrophils and in phagocytic index. Lysozyme level in serum was also decreased compared to that of control. The percentage of NBT-positive PMN cells decreased when the ceruloplasmin activity in plasma increased in intoxicated fish. PMID- 2311569 TI - Planar vector projection of short-latency median nerve somatosensory evoked potentials. AB - A planar vector projection of short-latency somatosensory evoked potentials (SEP) following stimulation of the median nerve was obtained by recording SEP over Fpz Oz and T3-T4 and plotting the amplitudes on both channels at corresponding time points against each other. The resulting curve showed three successive loops pointing ipsilateral occipital (N1), contralateral occipital (N2) and ipsilateral frontal (N3) to the stimulated side. Normal values for latency, amplitude and direction of these loops were obtained from 10 normal adults. N1 can be attributed to the cuneate nucleus and medial lemniscus, N2 to the primary somatosensory cortex and N3 to the frontal cortex. PMID- 2311571 TI - Visual and auditory evoked potentials in migraine. AB - We recorded visual (VEP) and brainstem auditory (BAEP) evoked potentials in 50 patients with clinically diagnosed common migraine attended by visual obscuration or sensory symptoms but no neurologic deficit. VEPs were recorded from Oz, 01, and 02 referenced to Fz, with replication of 200 repetitions of 1.88 per second checkerboard stimuli subtending a 56 minute retinal arc. Analysis time was 250 ms., and filter band pass was 1-250 Hz. BAEPs utilized rarefaction stimulation at 70 dB SL, with 150-3,000 Hz filter band pass and 10 ms. analysis time. Two thousand averages were recorded and replicated from Cz-A1 and Cz-A2. VEP N1, P1 and N2 latencies were longer in migraine patients than in controls, and VEP amplitudes were minimally greater. No significant differences were found between patients and controls, however. BAEP I-V and III-V interpeak latencies were significantly prolonged in migraine patients, and the degree of prolongation was greater on the left. Neither VEPs nor BAEPs exceeded clinical norms in migraine patients. VEPs and BAEPs are likely to add little to the clinical assessment of headache patients. BAEP differences may indicate dysfunction of brainstem centers, possibly related to endorphin or serotonin neurotransmission, and possibly related to the pathogenesis of migraine. The left sided asymmetry has been described previously and is of uncertain significance, but may also support a central mechanism for migraine. PMID- 2311570 TI - Diagnostic value of extensor digitorum brevis F-wave in L5 root compression. AB - The sensibility of F-wave in detecting lumbosacral radicular compression has been found to range from 65% to 18%. The present study was performed on 24 patients suffering from unilateral L5 compressive radiculopathy. The aim was to verify the reliability of extensor digitorum brevis (EDB) F-wave in the diagnosis of L5 root impairment, by using different parameters such as minimal, mean, maximal latency and the difference of these parameters between the affected and unaffected sides. In all patients conventional needle EMG was also performed bilaterally. While the needle EMG showed abnormalities in L5 innervated muscles of all patients, at least one of the different EDB F-wave parameters was found to be abnormal in only 7 patients (29.2%). Moreover no significant relation was observed between the severity of EMG and F-wave abnormalities. We conclude that conventional needle EMG appears to be the most useful electrophysiological technique in the diagnosis of L5 compressive radiculopathy, while EDB F-wave does not provide additional information. PMID- 2311572 TI - Median frequency estimates of paraspinal muscles: reliability analysis. AB - The technique of monitoring the frequency shift of the electromyographic signal through a single parameter, the median frequency (MF), was investigated with regard to its reliability characteristics as tested on two back muscle groups: the multifidus and iliocostalis lumborum. The proportion of variance in the MF parameters accounted for by the test/retest reliability as well as by the left versus right side analysis is satisfactory for the multifidus, it is, however, consistently lower for the iliocostalis. For the purpose of measuring muscular function, the MF recording technique appears to be well suited for clinical research, its application in the assessment of muscular dysfunction of back muscles is nevertheless far from simple. PMID- 2311573 TI - Effect of interelectrode recording distance on morphology of the antidromic sensory nerve action potentials at the finger. AB - In 15 normal subjects, antidromic median sensory compound nerve action potentials (SCNAPs) were recorded supramaximally from the middle finger with ring electrodes, using different interelectrode recording distances. The onset latencies were identical in all recording instances. The peak latency and amplitude of the major negative deflection continued to increase with increasing interelectrode distance. At and beyond a 4 cm interelectrode recording separation, they both achieved maximum values and did not increase further. On the other hand, the duration and area did continue to increase with increasing interelectrode separation. These findings suggest that in normal individuals, the true onset latency, peak latency, and amplitude are well reflected in the median SCNAP when it is recorded with an interelectrode distance of 4 cm or more at the finger; thus, they can easily be standardized. The SCNAP duration and area, however, are more variable since they both continue to change with increasing interelectrode recording separation without approaching a saturation value. PMID- 2311574 TI - Electrophysiologic evaluation of beri-beri polyneuropathy. AB - The diagnostic utility of electroneuromyography including F-wave and H-reflex was studied in 68 patients with peripheral polyneuropathy due to nutritional deficiency of thiamine. Out of all the electrophysiologic evaluations assessed, denervation activity in electromyography, prolonged conduction velocity and reduced motor nerve action potentials and prolonged H-reflex latency were the most frequently found abnormal findings, followed by reduced sural nerve action potential and, much less frequently, prolonged F-wave latency. In experimental thiamine-deficiency evoked polyneuropathy in chickens, the prominent abnormal findings were found in the leg muscles such as F-wave pathology and reduction and prolongation of peroneal and sciatic motor nerve action potentials, and also a prolongation of the distal sensory peroneal nerve latency respectively. PMID- 2311575 TI - Spatial and temporal patterns of transcription of a wound-induced gene in potato. AB - Transcriptional fusions between the gene encoding win2 from potato and the reporter gene encoding beta-glucuronidase (GUS) have been used to study the spatial and temporal patterns of wound induced gene activity in transgenic potato and tobacco plants. Gene fusions containing a full length win2 promoter were found to be correctly regulated in response to mechanical wounding in transgenic potato, but not in the heterologous host, tobacco. Sequences greater than 560 bp upstream of the transcription start site of win2 were shown to be important for wound inducibility. The dramatic induction of GUS activity detected using fluorometric assays of extracts of wounded and aged leaves of several independent win2--GUS transformants was consistent with the kinetics of win2 mRNA accumulation. Histochemical analysis of wounded leaves showed that transcription first occurred in cells immediately adjacent to the wound, and was then progressively induced in cells associated with the vascular system at a distance from the wound site. In tubers, a localized response to wounding was observed, and this only spread to other parts of the tuber if it had started to sprout. It was concluded that active vascular transport was necessary for the spread of wound response. Win2--GUS fusions were also expressed as part of normal plant development, as GUS activity was detected in the developing buds and in a layer of cells associated with the lenticels of unwounded tubers. PMID- 2311576 TI - The predicted amino acid sequence of alpha-internexin is that of a novel neuronal intermediate filament protein. AB - Our laboratory recently isolated and began to characterize a 66 kd rat brain cytoskeletal protein, dubbed alpha-internexin for its interactions in vitro with several other cytoskeletal proteins. Although alpha-internexin bore several of the characteristics of intermediate filament (IF) proteins, including the recognition by an antibody reactive with all IF proteins, it did not polymerize into 10 nm filaments under the conditions tested. Here we show that the predicted amino acid sequence of a cDNA encoding alpha-internexin shows the latter to be an IF protein, probably most closely related to the neurofilament proteins. Northern blotting shows that alpha-internexin expression is brain specific, and that rat brain alpha-internexin mRNA levels are maximal prior to birth and decline into adulthood, while the converse is seen for NF-L, the low molecular weight neurofilament subunit, suggesting that these two proteins play different roles in the developing brain. PMID- 2311577 TI - Amino acid sequence of a novel integrin beta 4 subunit and primary expression of the mRNA in epithelial cells. AB - Using the polymerase chain reaction, we have isolated cDNA clones that encode a new integrin beta subunit--beta 4. Its cDNA, which is 5676 bp in length, has one long coding sequence (5256 bp), a polyadenylation signal and a poly(A) tail. The deduced sequence of 1752 amino acids is unique among the integrin beta subunits. It contains a putative signal sequence as well as a transmembrane domain that divides the molecule into an extracellular domain at the N-terminal side and a cytoplasmic domain at the C-terminal side. The extracellular domain exhibits a 4 fold repeat of cysteine-rich motif similar to those of other integrin beta subunits. Certain features of the extracellular domain, however, are unique to the beta 4 subunit sequence. Of the 56 conserved cysteine residues found within the extracellular domain of other mature beta subunits, eight such residues are deleted from the beta 4 subunit sequence. The cytoplasmic domain is much larger (approximately 1000 amino acids) than those of other beta subunits (approximately 50 amino acids) and has no significant homology with them. A protein homology search revealed that the beta 4 subunit cytoplasmic domain has four repeating units that are homologous to the type III repetition exhibited by fibronectin. The beta 4 subunit mRNA was expressed primarily in epithelial cells. The restricted expression and the new structural features distinguish the integrin beta 4 subunit from other integrin beta subunits. PMID- 2311578 TI - Cloning and sequence analysis of beta-4 cDNA: an integrin subunit that contains a unique 118 kd cytoplasmic domain. AB - The alpha 6 beta 4 complex is a member of the integrin superfamily of adhesion receptors. A human keratinocyte lambda gt11 cDNA library was screened using a monoclonal antibody directed against the beta 4 subunit. Two cDNAs were selected and subsequently used to isolate a complete set of overlapping cDNA clones. The beta 4 subunit consists of 1778 amino acids with a 683 amino acid extracellular domain, a 23 amino acid transmembrane domain and an exceptionally long cytoplasmic domain of 1072 residues. The deduced amino-terminal sequence is in good agreement with the published amino-terminal sequence of purified beta 4. The extracellular domain contains five potential N-linked glycosylation sites and four cysteine-rich homologous repeat sequences. The extracellular part of the beta 4 subunit sequence shows 35% identify with other integrin beta subunits, but is the most different among this class of molecules. The transmembrane region is poorly conserved, whereas the cytoplasmic domain shows no substantial identity in any region to the cytoplasmic tails of the known beta sequences or to other protein sequences. The exceptionally long cytoplasmic domain suggests distinct interactions of the beta 4 subunit with cytoplasmic proteins. PMID- 2311579 TI - Members of the RCK potassium channel family are differentially expressed in the rat nervous system. AB - mRNAs encoding four members of the RCK potassium channel family, named RCK1, RCK3, RCK4 and RCK5 have been analyzed by RNA blot hybridization experiments using specific RNA probes. Each probe recognizes a single mRNA species, their sizes ranging from approximately 4600 nucleotides up to approximately 11,000 nucleotides. The expression of RCK mRNAs as well as their developmental appearance in different regions of the central and peripheral rat nervous system has been investigated. The two most abundant RCK potassium channel mRNAs (RCK1 and RCK5) are predominantly expressed in the adult nervous system. RCK3 and RCK4 mRNAs are present throughout all developmental stages studied. The temporal and regional patterns observed are specific for each RCK potassium channel mRNA indicating that specific regulation of expression occurs. Differential mRNA expression might provide one mechanism for the generation of potassium channel diversity in vivo. PMID- 2311580 TI - Expression of the acetylcholine receptor delta-subunit gene in differentiating chick muscle cells is activated by an element that contains two 16 bp copies of a segment of the alpha-subunit enhancer. AB - The acetylcholine receptor is a multimeric membrane protein whose expression is activated during muscle differentiation and upon denervation of adult muscle. To gain insight into the coordinate expression of receptor subunits during myogenesis we have analyzed the chick muscle receptor delta-subunit gene upstream region. The delta-subunit gene lacks canonical promoter elements (CCAAT and TATA boxes). Nuclease protection and primer extension analysis revealed that transcription starts at six major and several minor sites between -110 and -30 upstream of the translational initiation site; two sites, at positions -77 and 66, give rise to approximately 50% of all transcripts. Using nested deletions of the proximal 960 bp of the 5' flanking region of this gene we have identified a 62 bp sequence (-207 to -146) that activates transcription in a position independent manner. This enhancer-like element is activated during myotube formation; it contains two distinct functional moieties, each resembling the same 16 bp portion of the stage and tissue specific alpha-subunit gene enhancer which we have characterized previously [Wang et al. (1988) Neuron, 1, 527-534]. This common element, which also comprises several previously proposed skeletal muscle specific motifs [Buskin, J. N. and Hauschka, S. D. (1989) Mol. Cell Biol., 9, 2627-2640; Mar, J. H. and Ordahl, C. P. (1988) Proc. Natl. Acad. Sci. USA, 85, 6404-6408], may account for the coordinate expression of the two subunits. The cell specificity of the delta-subunit gene 5' flanking region is partly due to the enhancer, partly to an inhibitory element upstream of -207. PMID- 2311581 TI - The regulation of proenkephalin expression in a distinct population of glial cells. AB - The expression of opioid genes was examined in isolated populations of glial cells in primary culture. Northern blot analysis of purified type I astrocytes, oligodendrocytes and mixed oligodendrocyte-type-2-astrocyte lineage cells derived from cerebral cortex demonstrated robust expression of proenkephalin mRNA exclusively in type I astrocytes. The expression of proenkephalin mRNA was stimulated by the beta-adrenergic agonist isoproterenol, and 8-(4-chlorophenyl thio)adenosine 3'-5'-cyclic monophosphate (cpt-cAMP). Both of these compounds regulated a proenkephalin-chloramphenicol acetyltransferase fusion gene transiently transfected into type I astrocytes. HPLC and immunoassay of the cell culture media revealed significant levels of unprocessed proenkephalin secreted by the cell and this secretion was stimulated by isoproterenol and cpt-cAMP. The relatively high levels of proenkephalin expressed suggest that enhanced expression in astrocytes may be important during neural development, in trauma induced gliosis and in neuroimmune interactions. PMID- 2311582 TI - Domains involved in multimer assembly of von willebrand factor (vWF): multimerization is independent of dimerization. AB - The precursor protein of von Willebrand factor (pro-vWF) consist of four repeated domains, denoted D1-D2-D'-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2. The domains D1 and D2 constitute the amino-terminal pro-polypeptide and the remaining domains mature vWF, generated upon proteolytic processing. We have shown previously that the pro polypeptide of pro-vWF is obligatory for assembly of pro-vWF dimers into multimers, a process vital for efficient adhesion of platelets to an injured vessel wall. Here, we have employed full length vWF cDNA to construct a series of deletion mutants, based on the homology between the various domains. Specifically, the domains D', D3 or both were deleted and the multimeric pattern of the mutant vWF proteins was analysed after transient expression in COS-1 cells. It is demonstrated that in addition to the pro-polypeptide, both the D' and the D3 domain are required for multimer assembly. Furthermore, by analysing a construct containing only the domains D' and D3 next to the pro-polypeptide it is shown that this is the only part of the vWF protein involved in multimer assembly. Since, the formation of pro-vWF dimers relies on the carboxy-terminal area of mature vWF, it is concluded that multimer assembly is a process independent of dimerization. PMID- 2311583 TI - Phosphorylation at clustered -Ser-Pro-X-Lys/Arg- motifs in sperm-specific histones H1 and H2B. AB - Sea urchin sperm-specific histones H1 and H2B have distinctive N-terminal, and in the case of H1 also C-terminal, domains containing repeats of a basic motif (-Ser Pro-Lys/Arg-Lys/Arg- or a closely related sequence). The histones in spermatids (the precursors of sperm) are phosphorylated, and the unphosphorylated histones of mature sperm are rephosphorylated upon fertilization. These changes correlate with finely tuned changes in chromatin packing in the nucleus, and the domains responsible are evidently the N-terminal domains. We show that in spermatids there are six tandemly repeated phosphorylation sites in the N-terminal domain of H1 (a typical cAMP dependent protein kinase site is not phosphorylated) and that H2B is phosphorylated in the N-terminal domain at two or three sites in the case of H2B1 and four sites in H2B2. The consensus sequence for phosphorylation is Ser-Pro-X-Lys/Arg-, where X is Thr, Gln, Lys or Arg. There is an additional phosphorylated site in the C-terminal domain of H1 but most (or possibly all) copies of the consensus motif, which are here dispersed, are not phosphorylated. The negative charge introduced upon phosphorylation would be expected to weaken or abolish electrostatic interaction with DNA of this motif, which also occurs, and is phosphorylated, in somatic H1s. PMID- 2311584 TI - Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12. AB - The Myf-6 gene, a novel member of the human gene family of muscle determination factors has been detected by its highly conserved sequence coding for a putative helix-loop-helix domain. This sequence motif is a common feature of all Myf factors and other regulatory proteins. The new Myf gene is located on human chromosome 12, approximately 6.5 Kb upstream of the Myf-5 locus in a closely linked cluster of myogenic determination genes. Myf-6 cDNAs were isolated from human and mouse skeletal muscle, the only tissue in which expression of the corresponding mRNA was observed. In contrast to human primary muscle cell cultures which express moderate levels of Myf-6 mRNA, most established rodent muscle cell lines completely lack this mRNA. Myogenic 10T1/2 cells, however, induced by the expression of either pEMSV-Myf-4 or pEMSV-Myf-5 activate their endogenous mouse Myf-6 gene. Constitutive expression of Myf-6 cDNA in C3H 10T1/2 fibroblasts establishes the muscle phenotype at a similar frequency to the previously characterized myogenic factors. Moreover, muscle-specific CAT reporter constructs containing either the human myosin light chain (MLC) enhancer or the promoter of the embryonic myosin light chain gene are activated in NIH 3T3 fibroblasts or in CV1 kidney cells by cotransfection of Myf-6 expression vehicles. This transcriptional activation occurs in the absence of any apparent conversion of the cellular phenotype of the recipient cells. Glutathione-S transferase fusion proteins with Myf-3, Myf-4 or Myf-5 specifically bind to a MEF like consensus sequence present in the human MLC enhancer and the MLC1 emb promoter. In contrast, the Myf-6 hybrid protein interacts weakly with the same sequences showing lower affinity and reduced specificity. Since co-expressed pEMSV-Myf-6, nevertheless, is able to activate transcription of the MLC-CAT reporter constructs in non-muscle tissue culture cells, the different DNA binding properties in vitro might suggest that transactivation of gene expression by Myf 6 involves distinct binding sites and/or additional protein factors. PMID- 2311585 TI - Transcription factor E4TF1 contains two subunits with different functions. AB - The transcription factor E4TF1 stimulates transcription from the adenovirus early region 4 promoter by binding to a specific promoter element. E4TF1 has been purified to homogeneity from HeLa cells by sequence-specific DNA affinity chromatography and characterized. E4TF1 is composed of at least two distinct subunits identified as 60 kd and 53 kd polypeptides. The 60 kd protein alone is able to bind to the specific DNA sequence but not to stimulate transcription in vitro. The 53 kd protein alone neither binds to DNA nor stimulates transcription in vitro. However, the 53 kd protein is able to interact with the 60 kd protein and the interaction confers the ability to stimulate transcription in vitro and to increase the DNA binding affinity of the 60 kd protein. This study provides evidence that the interaction between the two different subunits of E4TF1 is required for it to function as a transcription factor, and that one of the subunits binds to a specific DNA sequence and the other works as a modulator. PMID- 2311586 TI - An unusual structure of a putative T cell oncogene which allows production of similar proteins from distinct mRNAs. AB - We previously identified a putative T cell oncogene on chromosome 11 near a translocation t(11;14)(p15;q11) in a human T cell tumour. The gene is transcribed from distinct promoters which have unrelated sequences, which occur within close but distinct methylation-free islands and which allow cell specific production of mRNA. The alternative first exons each contain a protein initiation codon from which two species of protein can be made, differing by only a single amino acid. The protein sequence is highly conserved between man and mouse (98%) and the same single codon difference between alternative first exons is also conserved. This is, therefore, a new form of eukaryotic gene organization from which similar proteins can be made from distinct mRNA species. PMID- 2311588 TI - Effects of L-carnitine administration on VO2max and the aerobic-anaerobic threshold in normoxia and acute hypoxia. AB - Seven healthy young male adults were subjected to a total of 56 tests to ascertain the effects of L-carnitine (L-C) and a placebo (P) on ventilation, O2 intake (VO2), CO2 output, heart rate, blood pressure and serum lactic acid, non esterified fatty acid, glycerol and glucose during strenuous and aerobic/anaerobic threshold-level treadmill exercise. The tests were made in conditions of normoxia (O2 = 20.9%) and hypoxia (O2 = 13.0%, equivalent to 3,500 m above sea level). The only clear difference was in the respiratory quotient (RQ = 0.883, SD 0.025 vs 0.904, SD 0.035) after L-C and P administration respectively (P less than 0.01), under normal oxygenation and 0.861, SD 0.052 following L-C vs 0.926, SD 0.040 after P (P less than 0.01) in acute hypoxia at VO2 levels around the anaerobic threshold. The lower RQ values of the L-C-treated subjects during hypoxia indicate a lower rate of carbohydrate transformation. PMID- 2311589 TI - Thermoregulatory responses to intermittent exercise are influenced by knit structure of underwear. AB - The purpose of this study was to evaluate the role of knit structure in underwear on thermoregulatory responses. Underwear manufactured from 100% polypropylene fibres in five different knit structures (1-by-1 rib, fleece, fishnet, interlock, double-layer rib) was evaluated. All five underwear prototypes were tested as part of a prototype clothing system. Measured on a thermal manikin these clothing systems had total thermal resistances of 0.243, 0.268, 0.256, 0.248 and 0.250 m2.K.W-1, respectively (including a value for the thermal resistance of the ambient environment of 0.104 m2.K.W-1). Human testing was done on eight male subjects and took place at ambient temperature (Ta) = 5 degrees C, dew point temperature (Tdp) = -3.5 degrees C and air velocity (Va) = 0.32 m.s-1. The test comprised a repeated bout of 40-min cycle exercise (315 W.m-2; 52%, SD 4.9% maximal oxygen uptake) followed by 20 min of rest (62 W.m-2). The oxygen uptake, heart rate, oesophageal temperature, skin temperature, Ta, Tdp at the skin and in the ambient air, onset of sweating, evaporation rate, non-evaporated sweat accumulated in the clothing and total evaporative loss of mass were measured. Skin wettedness was calculated. The differences in knit structure of the underwear in the clothing systems resulted in significant differences in mean skin temperature, local and average skin wettedness, non-evaporated and evaporated sweat during the course of the intermittent exercise test. No differences were observed over this period in the core temperature measurements. PMID- 2311587 TI - Tax1 induction of the HTLV-I 21 bp enhancer requires cooperation between two cellular DNA-binding proteins. AB - Activation of the HTLV-I promoter by the viral Tax1 transactivator is mediated by a 21 bp sequence motif imperfectly repeated three times and composed of three exactly conserved domains (A, B and C from 5' to 3'). We show here that the Tax1 response requires the integrity of the B domain and of at least one of the flanking A or C domains. We have identified three cellular proteins which bind specifically to the 21 bp motif. One of these is the already well-characterized transcription factor ATF. The other two, namely HEB1 and HEB2, are specific for the 21 bp motif. HEB1 can bind to either domain A or C, but binding of ATF and HEB2 is determined by domain B. However, neither domain B alone, nor ATF/CREB binding sites respond significantly to Tax1. We therefore propose that Tax1 induction of the 21 bp enhancer element requires interaction with the two different cellular proteins identified in this study: HEB1 and HEB2, rather than binding of the ATF factor. PMID- 2311590 TI - Muscle adaptation prior to recovery following eccentric exercise. AB - The effects of performing a second eccentric exercise bout prior to and after recovery from the first bout were compared. Twenty subjects performed 70 eccentric actions with the forearm flexors. Group A (n = 9) and group B (n = 11) repeated the same exercise 5 and 14 days after the initial bout, respectively. Dependent variables included muscle soreness, elbow joint angles, isometric strength, and serum creatine kinase (SCK). Subjects were tested pre-exercise and up to day 5 following each bout. The first bout produced significant changes in all measures for both groups (P less than 0.01). Values remained significantly different from baseline on day 5 when group A repeated the exercise (P less than 0.01) but were back to normal when group B performed bout 2. For both groups an adaptation occurred; significantly smaller changes in dependent variables were produced by the second bout, and recovery time was faster whether or not muscles were fully restored (P less than 0.01). The repeated bout did not exacerbate soreness, performance decrements, and elevation of SCK when performed by affected muscles that had not fully recovered from the first bout. Thus, the results suggest that an adaptation response had taken place prior to full recovery and restoration of muscle function following the initial eccentric exercise bout. PMID- 2311591 TI - Serum hormones and physical performance capacity in young boy athletes during a 1 year training period. AB - Serum hormones and physical performance capacity in boy athletes (AG; n = 19) were investigated during a 1-year training period (between the ages of 11.6 and 12.6 years). Six young untrained boys served as the control group (CG). The mean serum testosterone concentration increased significantly in AG (P less than 0.05) following the training period from 2.92 nmol.l-1, SD 1.04 to 5.81 nmol.l-1, SD 1.33. Significant differences were not observed in the cortisol, sex hormone binding globulin and growth hormone levels during the follow-up period. The AG clearly increased speed (P less than 0.001), speed-strength (P less than 0.01-P less than 0.001) and anaerobic capacity (P less than 0.001) whereas CG had only slight increases (NS) in physical performance capacity during a 1-year period. During the last 6-month training period significant positive correlations (r = 0.49-0.58; P less than 0.05-P less than 0.01) were observed in AG between the relative changes in testosterone, testosterone:cortisol ratio and growth hormone and the relative performance change in speed, maximal isometric force and endurance, respectively. At the end of the period significant positive correlations were observed in all subjects between the level of testosterone and speed-strength (r = 0.52-0.64; P less than 0.01-P less than 0.001) and anaerobic capacity (r = 0.49; P less than 0.05). It was concluded that an increase in anabolic activity with the synchronous training already has positive effects on trainability and physical performance capacity at an early stage in puberty. PMID- 2311592 TI - The energetics of middle-distance running. AB - In order to assess the relative contribution of aerobic processes to running velocity (v), 27 male athletes were selected on the basis of their middle distance performances over 800, 1500, 3000 or 5000 m, during the 1987 track season. To be selected for study, the average running velocity (v) corresponding to their performances had to be superior to 90% of the best French v of the season. Maximum O2 consumption (VO2max) and energy cost of running (C) had been measured within the 2 months preceding the track season, which, together with oxygen consumption at rest (VO2rest) allowed us to calculate the maximal v that could be sustained under aerobic conditions: vamax = (VO2max - VO2rest) x C-1. The treadmill running v corresponding to a blood lactate of 4 mmol.l-1 (vla4), was also calculated. In the whole group, C was significantly related to height (r = -0.43; P less than 0.03). Neither C nor VO2max (with, in this case, the exception of the 3000 m athletes) were correlated to v. On the other hand, vamax was significantly correlated to v over distances longer than 800 m. These v were also correlated to vla4. However vla4 occurred at 87.5% SD 3.3% of vamax, this relationship was interpreted as being an expression of the correlation between vamax and v. Calculation of vamax provided a useful means of analysing the performances. At the level of achievement studied, v sustained over 3000 m corresponded to vamax.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311593 TI - The influence of motor unit composition and stature on fractionated patellar reflex times in untrained men. AB - The purpose of the present study was to investigate the influence of muscle fibre composition and stature on fractionated patellar reflex times in ten healthy untrained men (mean age: 23.3 years, SD 3.1; mass: 65.9 kg, SD 8.5; height: 172.3 cm, SD 5.3). Biopsies were taken from the right vastus lateralis muscle. Using staining for myofibrillar adenosine triphosphatase after pre-incubation at pH 4.3 and 4.6, muscle fibres were classified into slow twitch (ST), fast twitch, oxidative-glycolytic (FTa) and fast twitch, glycolytic (FTb) fibres. Total patellar reflex time (TRT) and its fractionated components--reflex latency (LAT) and reflex motor time (MT)--were obtained from the mean of ten trials in each subject whilst performing Jendrassik's maneuvre. The TRT, LAT and MT were 77.7 ms, SD 16.5, 23.4 ms, SD 1.3 and 54.2 ms, SD 16.3, respectively. The LAT was significantly correlated to the percentage number of ST (r = 0.758, P less than 0.05) and FTa fibres (r = -0.657, P less than 0.05), fast twitch:slow twitch ratio (r = -0.799, P less than 0.01) and to the height of the subjects (r = 0.901, P less than 0.001), whereas TRT and MT were not significantly correlated with either fibre types or the height of the subjects. From these results it can be concluded that the LAT during the patellar reflex is influenced by muscle fibre composition and the length of the sensory and/or motor nerve. PMID- 2311594 TI - Finger and forearm vasodilatatory changes after local cold acclimation. AB - To determine the vascular changes induced by local cold acclimation, post ischaemia and exercise vasodilatation were studied in the finger and the forearm of five subjects cold-acclimated locally and five non-acclimated subjects. Peak blood flow was measured by venous occlusion plethysmography after 5 min of arterial occlusion (PBFisc), after 5 min of sustained handgrip at 10% maximal voluntary contraction (PBFexe), and after 5 min of both treatments simultaneously (PBFisc + exe). Each test was performed at room temperature (25 degrees C, SE 1 C) (non-cooled condition) and after 5 min of 5 degrees C cold water immersion (cooled condition). After the cold acclimation period, the decrease in skin temperature was more limited in the cold-acclimated compared to the non acclimated (P less than 0.01). The PBFisc was significantly reduced in the cooled condition only in the cold-acclimated subjects (finger: 8.4 ml.100 ml-1.min-1, SE 1.1, P less than 0.01; forearm: 5.8 ml.100 ml-1.min-1, SE 1.5, P less than 0.01) compared to the non-cooled condition. Forearm PBFexe was significantly decreased in the cooled condition only in the cold-acclimated subjects (non-cooled: 7.4 ml.100 ml-1.min-1, SE 1.2; cooled: 3.9 ml.100 ml-1.min-1, SE 2.6, P less than 0.05) indicating that muscle blood flow was also reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311595 TI - Fluid replacement drinks during high intensity exercise: effects on minimizing exercise-induced disturbances in homeostasis. AB - The purpose of these experiments was to examine the influence of various fluid replacement drinks on exercise-induced disturbances in homeostasis during heavy exercise. Nine trained cyclists performed constant load exercise on a cycle ergometer to fatigue on three occasions with 1-week separating experiments. The work rate was set initially at approximately 85% of VO2max (range 82-88%) with fatigue being defined as a 10% decline in power output below the initial value. During each experiment subjects consumed one of the following three beverages prior to and every 15 min during exercise: (1) non-electrolyte placebo (NEP; 31 mosmol.kg-1); (2) glucose polymer drink containing electrolytes (GP; 7% CHO, 231 mosmol.kg-1), and (3) electrolyte placebo drink without carbohydrate (EP; 48 mosmol.kg-1). Both the GP and EP beverage contained sodium citrate/citric acid (C) as a flavoring agent while C was not contained in the NEP drink. Although seven of nine subjects worked longer during the GP and EP treatment when compared with the NEP trial, the difference was not significant (P greater than 0.05). No differences (P greater than 0.05) existed between the GP and EP treatments in performance time. Exercise changes in rectal temperature, heart rate, delta % plasma volume and plasma concentrations of total protein, free fatty acids, glucose, lactate, potassium, chloride, calcium, and sodium did not differ (P greater than 0.05) between trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311596 TI - Reduction of saliva immunoglobulin levels by swim training. AB - Saliva immunoglobulin A (IgA) and cortisol levels were measured in 21 male members of a major midwestern swim team. Saliva samples were collected before and after training sessions four times during the fall season; the training intensity was light, moderate, heavy and during the taper period before a major competitive meet. Saliva IgA levels were decreased after each training session, reaching statistical significance with the moderate training intensity. Over the 3-month training period the pre-session and post-session IgA levels both decreased significantly during the heavy and taper training intensities later in the fall season. Cortisol levels were significantly elevated only after the heavy intensity training session. The Profile of Mood States (POMS) was used to assess the swimmers' overall mood on each test day. No significant correlations were found between the global POMS score and IgA or cortisol. Also, cortisol and IgA were not significantly correlated except after the light training session. Results from this study indicate that acute bouts of exercise can reduce salivary IgA levels and that chronic exercise of high intensity can reduce the resting levels of IgA. These changes may render the athletes more vulnerable to respiratory infections after exercise and even at rest during the later stages of the competitive season. PMID- 2311597 TI - Physiological effects of inspiratory resistance on progressive aerobic work. AB - The purpose of this study was to determine the potential effects on progressive aerobic work while breathing through a new military type chemical and biological (CB) respirator loaded with three different types of purifying canisters. Twelve healthy well-motivated male subjects (mean age 23 +/- 3 years) participated in the study. Results indicated that mean maximal oxygen uptake (VO2max), time to exhaustion, respiratory exchange ratio, rate of perceived exertion, respiratory rate and tidal volume at exhaustion, maximal lactate and the 2-min post-exercise lactate were not significantly influenced when breathing with the respirator and the canisters in comparison to a laboratory valve. Mean pulmonary ventilation, however, was reduced by 21% while oxygen and carbon dioxide ventilatory equivalents were significantly lower by 9% and 8% respectively. Review of the stage-by-stage responses to the treadmill test between the laboratory valve and respirator/canister conditions indicated no significant differences (NS) in oxygen uptake but slightly lower heart rates (NS). Ventilation was not influenced by the canisters until 80% of VO2max at which time the mean oxygen ventilatory equivalent became significantly lower. Blood lactate was significantly depressed between 60% and 90% VO2max under the respirator/canister conditions. It was concluded that, although physiological adaptation occurred, breathing with the new CB respirator and each of the three purifying canisters had no detrimental effect on progressive aerobic work to exhaustion. However, prolonged work at intensities greater than 80-85% of VO2max would in all probability be impaired when breathing with the CB mask and the canisters. PMID- 2311598 TI - Reproducibility of electromyographic patterns in stretch-shortening type contractions. AB - Within a set of repeated measurements, 12 male subjects performed the following types of muscle contraction: (1) running at constant velocity (12 km.h-1); (2) one-leg hopping at the frequency preferred; (3) both-legs hopping at the frequency preferred; (4) drop jumps from a height of 0.40 m. The surface electromyographs (EMG) from the left and right legs were recorded, together with the averaged signals from vertical ground reaction forces and angular displacement of the ankle joint. Reliability coefficients for the day to day and the week to week comparison were calculated. In addition, on any one test day the positions of the electrodes were systematically changed. The analysis of various EMG parameters (integrated-EMG) revealed high coefficients for both comparisons as well as for the total set of measurements. Qualitative comparisons of the EMG showed a high reproducibility of the shape of the patterns. If the relative position of the electrodes with respect to the belly of the muscle is changed, the amplitudes of the EMG recordings are markedly reduced. It is concluded that surface EMG is a reliable method for studies of the neuromuscular system. On the basis of the data presented, it is suggested that the term "reliability" should be replaced by the term "reproducibility" in order to cover both the aspect of the relative stability plus the aspects of linear changes and the scattering of the data in repeated measurements. PMID- 2311599 TI - Muscle hypertrophy and fast fiber type conversions in heavy resistance-trained women. AB - Twenty-four women completed a 20-week heavy-resistance weight training program for the lower extremity. Workouts were twice a week and consisted of warm-up exercises followed by three sets each of full squats, vertical leg presses, leg extensions, and leg curls. All exercises were performed to failure using 6-8 RM (repetition maximum). Weight training caused a significant increase in maximal isotonic strength (1 RM) for each exercise. After training, there was a decrease in body fat percentage (p less than 0.05), and an increase in lean body mass (p less than 0.05) with no overall change in thigh girth. Biopsies were obtained before and after training from the superficial portion of the vastus lateralis muscle. Sections were prepared for histological and histochemical examination. Six fiber types (I, IC, IIC, IIA, IIAB, and IIB) were distinguished following routine myofibrillar adenosine triphosphatase histochemistry. Areas were determined for fiber types I, IIA, and IIAB + IIB. The heavy-resistance training resulted in significant hypertrophy of all three groups: I (15%), IIA (45%), and IIAB + IIB (57%). These data are similar to those in men and suggest considerable hypertrophy of all major fiber types is also possible in women if exercise intensity and duration are sufficient. In addition, the training resulted in a significant decrease in the percentage of IIB with a concomitant increase in IIA fibers, suggesting that strength training may lead to fiber conversions. PMID- 2311600 TI - Osteomyelosclerosis following polycythemia vera: radiological-pathological correlation in a femur. PMID- 2311602 TI - Radiographic features of hand and wrist arthroplasties. AB - The normal and abnormal radiographic appearances of various arthroplasties of the hand and wrist have been presented. It is hoped that increased familiarity with these procedures and their radiographic features will lead to more meaningful radiographic interpretations by consulting radiologists. PMID- 2311601 TI - Quantitative thallium-201 myocardial exercise scintigraphy in normal subjects and patients with normal coronary arteries. AB - Quantitative thallium-201 myocardial exercise scintigraphy was tested in two patient populations representing alternative standards for cardiac normality: group I comprised 18 male uncatheterized patients with a low likelihood of coronary artery disease (CAD); group II contained 41 patients with normal coronary arteriograms. Group I patients were younger, they achieved a higher rate pressure product than group II patients; all had normal findings by physical examination and electrocardiography at rest and exercise. Group II patients comprised 21 females, 11 patients showed abnormal electrocardiography at rest, and five patients showed ischemic ST depression during exercise. Twelve patients had signs of minimal CAD. Twelve patients revealed abnormal visual and quantitative thallium findings, three of these patients had minimal CAD. Profiles of uptake and washout of thallium-201 were derived from both patient groups, and compared with normal limits developed by Maddahi et al. Furthermore, low likelihood and angiographically normal patients may differ substantially, and both sets of normal patients should be considered when establishing criteria for abnormality in exercise thallium imaging. When commercial software containing normal limits for quantitative analysis of exercise thallium-201 imaging is used in clinical practice, it is mandatory to compare these with normal limits of uptake and washout of thallium-201, derived from the less heterogeneous group of low-likelihood subjects, which should be used in selecting a normal population to define normality. PMID- 2311603 TI - Rectal duplications in children: a presentation of four cases. AB - Four cases with histologically proven duplication cysts of the rectum are presented. Two of these had communicating and two had closed rectal duplications. PMID- 2311604 TI - A giant abdominal bubble. PMID- 2311605 TI - A study of the variation of colonic positioning in the pararenal space as shown by computed tomography. AB - In a review of 1708 consecutive CT examinations of the abdomen the position of the ascending and descending colon in relation to the posterior and lateral edge of the kidney was studied. It was found that part of the colon was positioned posterior or posterolateral to the kidney's edge in percentages that varied between 14.2% and 0.9% in the different sex groups at the levels of upper, mid- and lower poles of the right and left kidney. It is concluded that this anatomical variation should be known if colon perforation is to be avoided during percutaneous nephrostomy or biopsy. PMID- 2311606 TI - Assessing resectability of lung cancer: the role of computed tomography of the mediastinum, upper abdomen and head. AB - In order to assess the value of computed tomography (CT) of the mediastinum, upper abdomen and head in the assessment of resectability of lung cancer, the CT findings of 262 patients, of whom 198 underwent thoracotomy, were analyzed retrospectively and the stagings obtained at CT and thoracotomy were compared. Mediastinal CT reliably predicted resectability when there was no evidence of mediastinal involvement. However, it was often impossible to determine whether tumour with apparent mediastinal infiltration on CT was resectable or not. The sole finding of lymph node enlargement did not permit differentiation of benign from malignant lymphadenopathy when the lymph node diameter was less than 25 mm and the lymphadenopathy was confined to one lymph node station. Upper abdominal metastases were found in 6.1% and brain metastases in 4.6% of patients and neither the histological type nor other features of the tumour were found to be useful predictors of their presence. The large number of non-specific findings decreased the utility of abdominal CT. The appropriate strategy for the pre operative evaluation of patients with lung cancer is discussed. PMID- 2311607 TI - Spontaneous pneumothorax as a complication of septic pulmonary embolism in intravenous drug addicts. PMID- 2311608 TI - Pneumothorax due to delayed rupture of traumatic trans-diaphragmatic gastric hernia. PMID- 2311609 TI - Unilateral hilar enlargement and oligemic lung secondary to mediastinal hydatidosis. PMID- 2311610 TI - Synthesized image processing in clinical neurosurgery. AB - In an effort to achieve efficient image management in clinical neurosurgery utilizing a local image filing system (EFPACS, Fuji Electric Co., Ltd), adequate image-processing and display techniques were developed. One is a method whereby the anatomical location of the thalamic and basal ganglion lesions is determined by automatically superimposing these lesions defined by magnetic resonance imaging (MRI) directly onto the Schaltenbrand-Wahren's human brain atlas. Horizontal, coronal and sagittal MR images are initially obtained based on the intercommissural line and a perpendicular erected on the midcommissural point as the basic reference coordinates. Precise superimposition is accomplished by the use of these reference axes. This imaging technique may offer the potential for help in anatomical identification of small intracranial lesions. Another technique described in the current communication is automated synthesis of two cerebral angiograms. By simply indicating two reference points, nasion and inion, with a cursor on the display screen, two films are automatically superimposed and displayed as a single synthesized image, featuring two different vascular phases simultaneously by a positive(vein)-negative(artery) mode. This technique was applied to patients with complete occlusion of the middle cerebral artery with or without sufficient blood flow through collateral circulation and was found useful in evaluating basic hemodynamics on a single angiographic image. PMID- 2311611 TI - Radiographic changes of the revascularized femoral head. AB - Twenty-two necrotic femoral heads in young adults were radiologically followed-up after grafting with vascularized bone by comparing the preoperative and the postoperative state of the hip joint. Three parameters were observed and followed; the flattening of the femoral head; the degree of osteoarthrosis of the joint; and the degree of incorporation of the graft into the recipient bone. The results, expressed by index figures, showed that the femoral head flattened during the first two years postoperatively; that the maximal incorporation occurred during the same period of time; and that the appearance of postoperative osteoarthrosis was slow during the first year and increased subsequently. This numerical characterization of radiological findings allows systematic individual analysis after revascularization of the femoral head with bone grafts. It is also suited for comparisons between patients, between series of patients and of various treatment techniques. Furthermore, this quantification provides a numerical index that seems to correlate with the outcome of the treated hip joint. PMID- 2311612 TI - Long-term performance of Starr-Edwards silastic ball valves and St Jude Medical bi-leaflet valves. A comparative analysis of implantations during 1980-86 for aortic stenosis. AB - Long-term performance of Starr-Edwards silastic ball (SESB, n = 168) and St Jude Medical bi-leaflet (SJMB, n = 93) valves in patients who were alive 30 days after implantation (1980-86) for aortic stenosis was compared. Mean follow-up was 3.0 years (0.1-7.9 years). The SESB and SJMB groups differed as regards female gender (18% vs 47%, P less than 0.0001), NYHA classes III-IV (59% vs 72%, P less than 0.05), coronary artery disease (CAD, 32% vs 62%, P less than 0.01) in patients with coronary arteriography (n = 82 and n = 55, respectively), and prosthetic annulus diameter (26 +/- 1 vs 23 +/- 2 mm, P less than 0.0001). Five-year survival +/- SE in SESB vs SJMB patients was: total population, 89 +/- 3% vs 80 +/- 6% (NS); coronary arteriography population, no CAD, 90 +/- 4% vs 100% (NS), and with CAD, 71 +/- 11% vs 60 +/- 13% (NS; P = 0.01 for CAD). Five-year event free survival +/- SE in SESB vs SJMB patients was 95 +/- 2% vs 97 +/- 2% (NS) for thromboembolism, 95 +/- 2% vs 89 +/- 4% (NS) for coumadin-related haemorrhage, 98 +/- 1% vs 99 +/- 1% (NS) for endocarditis, 98 +/- 1% vs 94 +/- 5% (NS) for paravalvular leak, 88 +/- 3% vs 79 +/- 6% (NS) for all valve-related complications, and 98 +/- 1% vs 95 +/- 4% (NS) for prosthesis replacement. Thrombotic occlusion or structural failure were not observed. No patients without CAD experienced thromboembolic events. Cox regression analyses (in both total population and coronary arteriography population) of survival as well as the various complications revealed that the type of prosthesis did not have predictive influence. CAD was an independent risk factor for thromboembolism, haemorrhage, and all valve-related complications. Previous systemic hypertension was independently predictive of haemorrhage. The SESB and SJMB prostheses showed comparable and acceptable long-term performance. Only patient-related variables, notably CAD, influenced late results. The proven durability and relatively low price of the SESB valves together with the excellent haemodynamic performance of even small-sized SJMB valves should be considered in the light of the present results. PMID- 2311613 TI - Effect of acetylcholine on arterial and venous grafts and coronary arteries in patients with coronary artery disease. AB - Endothelium-dependent vasomotor responses differ in arteries and veins. The transfer of a given vessel from a different vascular bed into the coronary circulation by grafting may affect its endothelial function. In order to evaluate the differences in endothelial function of the internal mammary artery and aortocoronary venous grafts in patients with coronary artery disease, the response to acetylcholine (ach) was examined and compared with that of native coronary arteries. Eighteen patients were examined, including eight with internal mammary artery grafts (9 days to 48 months after surgery), and 10 with saphenous vein grafts (12-96 months after surgery). Ach (70-700 nmol min-1) was infused selectively into a graft on the left anterior descending coronary artery, and the effect on vessel diameters was assessed by quantitative arteriography. In both groups 84% and 83%, respectively, of the arterial segments distal to the bypass anastomosis were contracted by ach (greater than or equal to 70 nmol min-1). The segments of both groups did not show angiographic evidence of local atherosclerosis. A complete occlusion occurred in four cases. In contrast, internal mammary artery grafts were not contracted by ach; in four of 12 segments a dilatation was observed, whereas five of 20 aortocoronary venous graft segments showed a slight reduction in lumen diameter after the highest ach dose applied. The vasoconstricting effect of ach was reversed by intracoronary nitroglycerin. By using ach as an indicator of endothelial dysfunction it is concluded that the internal mammary artery grafts maintained an intact endothelial function after surgery, whereas the coronary artery segments showed an impaired endothelium dependent vasodilatation. Some of the venous graft segments reacted as coronary arteries did with a less pronounced cholinergic vasoconstriction. This in vivo study supports the observation of a functional superiority of internal mammary artery over saphenous vein coronary grafts. PMID- 2311614 TI - Transient myocardial ischaemia: a multivariate analysis on clinical, angiographic and ergometric variables. AB - The availability of ambulatory ECG monitoring allows identification of transient myocardial ischaemia, the clinical relevance of which is currently being investigated. Ninety-four consecutive patients with ischaemic heart disease and a positive exercise test (greater than or equal to 1 mm ST-segment depression) were studied to evaluate the prevalence of transient myocardial ischaemia (either painless or painful) during 24-h dynamic electrocardiogram (ECG) and the clinical, angiographic and ergometric variables predicting its appearance. Two hundred-and-eighty-one episodes of transient electocardiographic myocardial ischaemia were recorded in 69 patients (73.4% of all patients). Transient myocardial ischaemia was more frequent, although not significantly so, in patients with diabetes, with previous myocardial infarction, or with multivessel disease. When tested by multivariate analysis, neither the clinical variables nor the severity of coronary artery disease allowed prediction of the occurrence of transient myocardial ischaemia during dynamic ECG. The duration of exercise testing up to the ischaemic threshold (ST-segment depression = 1 mm) and the peak heart rate during exercise were more accurate predictors of transient myocardial ischaemia (P = 0.019 and 0.012 respectively). Patients with transient myocardial ischaemia had a lower ischaemic threshold (355 +/- 175 vs 498 +/- 150 s, mean +/- SD, P = 0.001) despite a lower peak heart rate (129 +/- 18 vs 137 +/- 12 beats min-1, P = 0.047) than patients without transient myocardial ischaemia. In conclusion, exercise testing may help select patients for examination by dynamic ECG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311615 TI - Thallium-201 scintigraphy after dipyridamole infusion with low level exercise. II. Quantitative analysis vs visual analysis. AB - To determine the value and limitations of quantitative analysis of thallium-201 imaging after intravenous dipyridamole in combination with low level exercise, 81 patients with suspected coronary artery disease (CAD) were evaluated prospectively. The results of quantitative analysis were compared with the results of visual analysis. All patients underwent coronary arteriography and left ventricular angiography. Significant CAD was present in 59 patients (73%); multivessel CAD was observed in 33 patients (42%). Mild side-effects such as headache, vertigo and nausea were experienced by 12 patients (15%). To establish 'test-specific' normal limits in quantitative analysis of uptake and washout of thallium-201 after dipyridamole infusion with low level exercise we studied 20 healthy volunteers with a likelihood of CAD less than or equal to 1%. Sensitivity and specificity of quantitative analysis for overall detection of significant CAD were 76% and 73%, respectively vs 78% and 86%, respectively with visual analysis (P = NS). Sensitivity for the detection of multivessel CAD was slightly higher with quantitative analysis (73%) than with visual analysis (70%), but the specificity was lower (75% vs 92%) (P = NS). Sensitivity of quantitative analysis in relation to vessels involved was slightly lower than with visual analysis (RCA and LAD: P = NS; LCX: P less than 0.05). Of 14 patients with false-negative results, four had multivessel CAD. Thus, quantitative analysis after the combination of dipyridamole infusion with low level exercise did not improve the diagnostic value as assessed by semi-quantitative visual analysis. PMID- 2311616 TI - Fourier analysis of ventricular fibrillation of varied aetiology. AB - Fast Fourier Transform analysis was used to study ventricular fibrillation induced by several different methods in 43 greyhounds anaesthetized with sodium pentobarbitone. The dominant frequency at the body surface of ventricular fibrillation induced electrically in non-ischaemic hearts was initially 9.9 +/- 0.7 Hz, remained above 9 Hz for 70 s and then rapidly fell to 5 Hz. The dominant frequency of ventricular fibrillation induced by acute occlusion (initially 12.3 +/- 0.2 Hz), or by reperfusion (12.2 +/- 0.4 Hz) of the anterior descending branch of the left coronary artery, showed a similar time-course. However, ventricular fibrillation induced by administration of potassium (4.8 +/- 0.8 Hz) or ouabain (7.1 +/- 1.1 Hz) was significantly slower. Fibrillation recorded from the endocardium of the heart initially showed a similar dominant frequency to that recorded at the body surface, but there was no significant fall in frequency over 3.3 mins. There was little difference in the time-course of fibrillation in the non-ischaemic heart recorded directly from the epicardium or from a surface lead. These findings may be of relevance to the poor response to DC countershock after prolonged ventricular fibrillation, hyperkalaemia or cardiac glycosides. PMID- 2311617 TI - Clinical outcome and left ventricular function 23 years after acute coxsackie virus myopericarditis. AB - The clinical outcome of 18 patients, who presented with a Coxsackie virus myopericarditis in 1965, was evaluated 23 years later. Five patients had died, two of them had had heart failure. Thirteen patients and 23 healthy control subjects underwent exercise testing with gas exchange analysis. Left ventricular (LV) peak filling rate (PFR) was estimated by digitized M-mode echocardiography. Left ventricular ejection fraction was measured at rest and during exercise by radionuclide angiography. All patients were free of cardiac symptoms. Their clinical examination and the chest X-ray were normal. Peak oxygen consumption was not decreased in the patient group compared with the control group. PFR was significantly lower in the patient group than in the control group, 10.2 +/- 0.4 vs 13.2 +/- 0.4 cm s-1, P less than 0.001 (mean +/- SEM). LV ejection fraction was normal at rest in all patients (58 +/- 1%). An abnormal LV ejection fraction response to exercise was observed in two patients. Our data indicate that long term prognosis after acute Coxsackie virus myopericarditis is good in a majority of patients. PMID- 2311618 TI - Doppler-echocardiographic findings in a patient with persisting right ventricular sinusoids. AB - The Doppler-echocardiographic features of persisting right ventricular myocardial sinusoids are presented. An 18-year-old patient with persisting right ventricular sinusoids had undergone comissurotomy for critical pulmonary artery stenosis at the age of 12 months. Follow-up catheterization at the age of 17 years revealed no signs of residual pulmonary artery stenosis, outflow tract obstruction or pulmonary hypertension. No shunt could be documented. High systolic velocity jets within the myocardial sinusoids were recorded by means of continuous-wave Doppler. Pulmonary artery blood flow velocity was recorded mainly consequent to atrial contraction and was reduced during right ventricular ejection period, thus reflecting impaired systolic and diastolic right ventricular function. PMID- 2311619 TI - Aortic valve area evolution after percutaneous aortic valvuloplasty. A prospective trial using a combined Doppler echocardiographic and haemodynamic method. AB - The aortic valve area was serially evaluated in 45 patients, mean age 78 years, suffering from severe aortic stenosis who underwent percutaneous aortic valvuloplasty. The aortic valve area was calculated from haemodynamic data prior to and immediately after the procedure using the mean gradient. Serial determinations of the aortic valve area were also obtained 1 day before, 1 day after and 2 months after valvuloplasty from the thermodilution cardiac output and Doppler echocardiography mean left ventricle-to-aorta gradient. The mean gradient significantly decreased from 75 +/- 24 to 42 +/- 16 mmHg (P less than 0.01) when measured from haemodynamic data and from 63 +/- 20 to 41 +/- 13 mmHg (P less than 0.01) when estimated from Doppler-derived data. It rose to 48 +/- 15 mmHg at 2 months (NS). The aortic valve area increased significantly from 0.48 +/- 0.13 to 0.67 +/- 0.29 cm2 (P less than 0.01) when calculated from haemodynamic data, and from 0.53 +/- 0.18 to 0.74 +/- 0.23 cm2 (P less than 0.01) when estimated from Doppler-derived data. It declined to 0.69 +/- 0.27 cm2 at 2 months (NS). Aortic valve area values determined from haemodynamic data and from Doppler-derived data correlated well before valvuloplasty (r = 0.80, P less than 0.01) but poorly afterwards (r = 0.57, P less than 0.01). The aortic valve area was not influenced by valvuloplasty in eight patients. At 2 months, restenosis was apparent in eight patients out of 32 that were re-evaluated. Three patients died within 5 days of the procedure. After an average 12 months' follow-up, eight more patients died. Symptoms were not influenced or recurred in 17 patients, while 17 others remained improved by at least one NYHA functional class. Seven patients were operated on, and there was one operative death. The calculated aortic valve area was significantly greater at the end of the procedure in the patients with persistent improvement compared with those with a poor result (0.83 +/- 0.29 cm2 vs 0.65 +/- 0.14 cm2, P less than 0.05). In conclusion, in this study one third of the patients submitted to percutaneous aortic valvuloplasty had no objective improvement in calculated valve area or early restenosis after 2 months. Functional improvement was observed in one third of the patients. Immediate re estimation of the aortic valve area from haemodynamic data at the end of the procedure may not reflect the actual effect of valvuloplasty on the aortic orifice. PMID- 2311620 TI - PET in clinical cardiology: can we already swim? PMID- 2311621 TI - In vivo imaging of rat lymphocytes with an indium 111-labelled anti-T cell monoclonal antibody: a comparison with indium 111-labelled lymphocytes. AB - An indium 111-labelled mouse anti-rat T cell monoclonal antibody, MRC OX-19, was injected intravenously into rats to establish the usefulness of radiolabelled anti-lymphocyte antibodies in imaging lymphoid tissues. Antibody binding in vivo, measured by immunofluorescence analysis of cell suspensions made from lymphoid tissues, was detectable on lymphocytes in blood, spleen and lymph nodes. The extent of binding was time and antibody-dose dependent. Doses of antibody above 80 micrograms/kg body weight resulted in modulation, i.e. loss of CD 5 (T1) molecules from the cell surface, although the cells remained in the circulation. Modulation was demonstrable within 2 h and for at least 24 h after a single injection of antibody. Intravenous injection of 111In-MRC OX-19 resulted in levels of in vivo binding comparable with those seen with unlabelled antibody. Scintillation imaging showed early splenic localisation persisting over 48 h, a more gradual localisation in the lymph nodes seen clearly at 24 h and a steady background. Comparison of the in vivo distribution of labelled antibody and 111In tropolone-labelled lymphocytes showed that both could be used for external imaging of lymphocytes by scintillation camera. PMID- 2311622 TI - Quantification of the whole-body distribution of PET radiopharmaceuticals, applied to 3-N-([18F]fluoroethyl)spiperone. AB - Using a multi slice whole body PET scanner PC4096-15WB, diagnostic measurements of the cerebral distribution of the D2 receptor ligand 3-N ([18F]fluoroethyl)spiperone were extended to quantify the biodistribution of this PET radiopharmaceutical. As a rotating line source was used for measured attenuation correction, transmission scans could be combined with emission scans even after injection of the tracer. Only 1% of the total administered dose (TAD) was found in the whole brain at 180 min, but the striatum and pituitary were still excellently delineated. Urinary bladder, gall bladder, and liver were the organs with the highest TAD ranging from 6% to 25%. The gall bladder is the critical organ with an absorbed dose of about 200 muGy/MBq followed by the urinary bladder and liver with 83 and 66 muGy/MBq, respectively. In the rest of the body radioactivity was evenly distributed. The total body dose was found to be 11.9 muGy/MBq. PMID- 2311623 TI - 81mKr equilibrium radionuclide ventriculography for the assessment of right heart function. AB - Right heart 81mKr equilibrium radionuclide ventriculography was used to derive right ventricular ejection fraction (RVEF) in 12 healthy male volunteers. Anatomical lung subtraction using 99mTc-MAA perfusion scintigraphy was compared with conventional background correction and the effect of imaging projection on the techniques of image analysis evaluated. Both intra and inter observer variability were reduced by anatomical lung subtraction when compared to conventional background correction. In the right anterior oblique (RAO) projection, background corrected RVEF was lower than lung subtracted RVEF - 0.544 +/- 0.05 and 0.612 +/- 0.08 (mean +/- SD) (P less than 0.02). Lung subtracted RVEF in the anterior projection was lower than that with background correction (P less than 0.05) and lower than lung subtracted RVEF in the RAO projection (P less than 0.001). We conclude that optimal separation of right heart structures is achieved in the RAO projection and that reproducibility of the analytical technique is improved by anatomical lung subtraction. PMID- 2311624 TI - The orthopan tomoscintigram--a new application of emission computed tomography for facial bone scanning. AB - The exact regional correlation of findings of facial bone scans, planar or SPECT, to dental orthopan X-ray films (OPT) is difficult because of the very different projection techniques. To improve correlative imaging in this regard a projection algorithm was developed that uses SPECT data of the skull for reconstructing an orthopan tomoscintigraphic projection. Fourteen conventional SPECT slices of the upper and lower jaws were obtained during bone scanning. All mandibular slices were superimposed resulting in a horseshoe shaped structure, while was marked by an ROI which was divided into segments. All 14 SPECT slices were then masked by this segmental ROI, thereby marking the teeth-carrying bone in all slices. The information from this horseshoe like ROI is then transformed into lines. Line by line arrangement results in an orthopan projection, the orthopan tomoscintigram. This new display allows 1:1 true scale superimposition with the X-ray OPT and markedly facilitates correlative imaging. PMID- 2311625 TI - A case of pyloric atresia associated with junctional epidermolysis bullosa. AB - We describe an infant with congenital pyloric atresia associated with junctional epidermolysis bullosa, which is now recognized as an autosomal recessive syndrome. Laparotomy revealed a membrane in the pyloric antrum. Clinical manifestations included intractable diarrhoea and malnutrition due to protein losing gastroenteropathy. A satisfactory nutritional state could not be obtained during the clinical course and the child died. PMID- 2311626 TI - Modified Greulich-Pyle, Tanner-Whitehouse, and Roche-Wainer-Thissen (knee) methods for skeletal age assessment in a group of Italian children and adolescents. AB - Modified Greulich-Pyle (GP), Tanner et al. 2, radius, ulna and short bones (TW2 RUS), TW2-20-bone and Roche-Wainer-Thissen RWT (knee) skeletal age assessments were made in an Italian population sample of 128 males and 93 females aged 4.1 16.9 years. All the scales appear to be well-suited to the Italian population despite minor differences. A very high correlation was found between the assessment of knee skeletal ages by the RWT method and that of the hand-wrist by the GP and TW2 systems in the same subject without sex and age-associated variations. PMID- 2311627 TI - Longitudinal study of blood pressure during the 1st year of life. AB - Systolic and diastolic blood pressure (BP), heart rate and weight were measured in 260 boys and 254 girls, from birth to 12 months of age. Mean +/- SD values of parameters studied and percentile curves are reported. Systolic and diastolic BP increase significantly during the first 6 months of life and are poorly correlated with weight. In the 1st month of life the diastolic BP values are lower than those reported by others. PMID- 2311630 TI - A new case of hyperargininaemia: neurological and biochemical findings prior to and during dietary treatment. AB - We present clinical and biochemical data on a further patient with hyperargininaemia and the results of neurophysiological tests both before and during dietary treatment with an essential amino acid mixture. With normalisation of plasma arginine concentrations, neurological functions improved and brain stem auditory evoked potentials normalized suggesting a partially reversible central conduction disorder. Neuroradiological findings included cerebral cortical atrophy on computed tomography scan and patchy abnormal myelination on magnetic resonance imaging (MRI). The typical clinical picture is discussed with reference to published therapeutical trials. PMID- 2311629 TI - Detection of HIV RNA by in situ hybridization in peripheral blood mononuclear cells of seronegative children born to HIV-infected mothers. AB - Of 44 children born to human immunodeficiency virus (type 1) (HIV)-infected mothers, 11 have become seronegative. After the loss of maternal antibodies all children were analysed for several immunological functions and virological parameters in order to determine their HIV status. All children to date are clinically healthy and have normal immune functions. HIV-1 was detected by p24 antigen in one child, by in situ hybridization in nine children while viral cultures were all negative. These data suggest that the rate of vertical transmission of HIV-1 may be underestimated if seronegative children are considered to be not infected. They also suggest that molecular biological techniques are more sensitive than HIV antigen assay or viral cultures. PMID- 2311628 TI - Diffuse neonatal haemangiomatosis: successful management with high dose corticosteroids. AB - We report two cases of diffuse neonatal haemangiomatosis. The multiple cutaneous lesions were associated with massive hepatic involvement and congestive heart failure in one, while in the other laryngeal haemangiomas caused stridor and inspiratory distress. A significant regression in vascular lesions was achieved with high dose corticosteroid therapy. PMID- 2311631 TI - Secondary amyloidosis in glycogen storage disease type Ib. AB - We observed the development of generalized amyloidosis in a girl with glycogen storage disease type Ib (GSD-Ib) who showed neutropenia, neutrophil dysfunction and recurrent infections. Renal and thyroid biopsies showed secondary amyloidosis, characterized by the presence of potassium permanganate sensitive Dylon positive deposits in glomeruli, renal vessels and thyroid interstitium. Immunohistochemistry showed that the deposits were composed of amyloid A (AA) protein. Possibly neutrophil abnormalities are involved in the pathogenesis of amyloidosis. PMID- 2311632 TI - Neonatal polycythaemia: effect of partial dilutional exchange transfusion with human albumin on whole blood viscosity. AB - Haematocrit (HCT) and viscosity of whole blood were measured in ten polycythaemic hyperviscous newborn infants both before and after dilutional partial exchange transfusion with 5% albumin. This was performed in order to evaluate the effect on the lowering of HCT and whole blood viscosity. Mean umbilical HCT values decreased from 68.7% before, to 54.4% post transfusion. This decrease in HCT and viscosity was highly significant (P less than 0.001). Safety and lack of complications make human albumin solution superior to human plasma for exchange transfusion in neonatal polycythaemia. PMID- 2311633 TI - Home monitors for infants: use, misuse, and "over-the-counter" use. AB - The prevalence of "over-the-counter" monitors, was surveyed in infants referred to five Belgian paediatric centres between September 1987 and March 1988 for evaluation of their risk for sudden infant death (SID). Questionnaires were collected from 1625 families. Of the infants, 8.9% were already being monitored at home. For 78.1% of the infants no medical advice had been solicited, and for 21.9%, a paediatrician or a general practitioner had advised home monitoring without previous evaluation. Forty of 824 infants referred with no history of SID, and no history of apparent life-threatening event (ALTE), were monitored (4.8%). Monitoring was started for 3.8% (5 out of 130) of the infants who had lost a cousin or an uncle to SID, and for 22.2% (69 of 310) of the younger siblings of a SID victim. Of the 341 infants who had presented with an ALTE, monitoring was started in 32 (9.4%). The infants were monitored with respiratory monitors only, and in 86% of the monitors, the alarm delay had been regulated unnecessarily low. PMID- 2311635 TI - 4th Symposium on a Long Term Clinical Care of Parkinson's Disease. Tokyo, April 22, 1989. Proceedings. PMID- 2311634 TI - Treatment of iron overload in children and adolescents on chronic haemodialysis. AB - Treatment of secondary haemosiderosis with desferrioxamine (DFO) was evaluated in children and adolescents treated by chronic haemodialysis. Ten patients were treated with intravenous DFO (25 mg/kg body weight). Three patients received DFO throughout dialysis, four were treated only during the last hour of each dialysis session, and three other patients were successively treated with DFO according to both regimens. A significant decrease and normalisation of serum ferritin was achieved only with DFO administered during the last hour of dialysis. In some patients blood haemoglobin (Hb) increased during treatment. Although serum ferritin levels remained normal, Hb levels returned to pretreatment values following discontinuation of DFO treatment. Visual and auditory neurotoxicity was not noticed but increased systemic infections were observed. PMID- 2311636 TI - Factors affecting survival in primary superficial bladder cancer. AB - In a retrospective study of 345 patients with primary superficial transitional cell carcinoma of the bladder, factors present at the time of initial evaluation and which affect survival were identified. All patients were treated initially by transurethral resection with separate resection of the tumor base and margin. 89 patients received no further treatment after resection of the tumor, 256 patients received adjuvant topical instillation therapy over a period of 6 weeks. The distribution of risk factors in both groups was comparable; the survival rate after 5 years showed no significant difference. The tumor-related mortality rate was 12.5%. The Cox regression model showed carcinoma in situ in the tumor margin and the absence of a tumor-associated tissue inflammatory reaction to be the most important risk factors. Beside these associated risk factors, poor differentiation of the tumor parameter was the most important prognostic factor. PMID- 2311637 TI - Bacillus Calmette-Guerin treatment and vesicorenal reflux. AB - 14 patients with radiologically documented vesicorenal reflux (5 bilateral, 7 unilateral, 2 unilateral double-J stents) received intravesical immunotherapy with bacillus Calmette-Guerin (BCG) after treatment of their superficial urothelial tumors. 1 patient with a double-J stent suffered a highly febrile attack following obstruction of the indwelling ureteral catheter. The other patients tolerated 1 or 2 (6 of 14 patients) courses of BCG without an increase in side effects. Topical intravesical therapy with BCG in patients with vesicorenal reflux seems to be indicated in view of the multicentricity of urothelial carcinoma and can be performed without an increased risk of complications. PMID- 2311638 TI - Bladder dysfunction after simple hysterectomy: urodynamic and neurological evaluation. AB - Many women presenting with symptoms of bladder dysfunction relate their onset to the operation of simple hysterectomy. This study reviews the urodynamic findings in 126 women who had a simple hysterectomy, of whom 25 also had sacral reflex latencies measured. The results show that 47.0% had detrusor instability, 36.7% had urethral obstruction, and 24.8% stress incontinence. These findings are statistically significant when compared to controls. 80% of the women who underwent measurement of sacral reflex latencies had evidence of nerve conduction abnormality. PMID- 2311639 TI - Vescica Ileale Padovana: a technique for total bladder replacement. AB - A new technique for detubularized and originally reshaped ileal total bladder replacement following radical cystectomy for bladder cancer is described and named 'Vescica Ileale Padovana'. 16 patients have been clinically, radiologically and urodynamically evaluated with a follow-up ranging from 4 to 18 months (mean 10 months). The complication rate was low: 1 ureteroileal stenosis; 2 urethroileal strictures. Daytime continence was perfect in 87% (14 of 16 patients). Nighttime continence was perfect (dry sleep for 6-7 h) in 81% (13 of 16 patients). The reservoir features were: high capacity (400-650 ml); low pressure (mean pressure at capacity 17 cm H2O no pressure waves in 50% of patients 30-50 cm H2O wide pressure waves with 250-ml threshold volume in 50%); absence of reflux; complete voiding by abdominal straining, and perineal relaxation. PMID- 2311640 TI - Morphometry in human transitional cell bladder cancer. Nuclear area and standard deviation of nuclear area--relation to tumor grade (WHO) and prognosis. AB - A retrospective follow-up (range 9.4-22 years, mean 13 years) study of 83 patients with grade I-III (WHO) bladder carcinomas was performed. Nuclear area (mean +/- SD 59.7 +/- 18.7 microns2) and the SD of nuclear area (mean +/- SD 19.7 +/- 13.4 microns2) were determined by using morphometric methods. The SD of nuclear area and histopathological grade exhibited a clearly significant relation, the relation between grade and nuclear area was weaker. The number of recurrences in the bladder and the recurrence-free period were not significantly related to histopathological grade, mean nuclear area or SD of nuclear area. The progress in nodal or metastatic stage could be predicted by histopathological grade, mean nuclear area and SD of the nuclear area. Prediction of crude survival, however, was not efficient. When only bladder cancer deaths were included in the analysis, histopathological grade (p less than 0.001), mean nuclear area (p = 0.011) and SD of the nuclear area (p = 0.001) showed a significant relation to survival. Grade II tumors could be divided into two prognostically different groups using nuclear area and SD of the nuclear area as classifiers. The results suggest that morphometric parameters are as good as histopathological grade in predicting long-term prognosis of bladder carcinomas, and better than the histopathological grade in predicting progress in nodal (N) or metastatic (M) stage. PMID- 2311642 TI - Idiopathic hematoma of the epididymis: presentation of three cases. AB - Three cases of idiopathic hematoma are reported for the first time. The disease presented with clinical symptoms of epididymitis and was unsuccessfully treated with antibiotics. The persistence of the symptoms and the suspicion of tumor led to the removal of the lesioned epididymides. The etiology of these hematomas and their differential diagnosis in relation with other benign processes of the epididymis are discussed. PMID- 2311641 TI - Increased immunogenicity of human renal carcinoma cells following treatment with cholesterol derivatives. AB - Tumor cells isolated from human renal cell carcinoma biopsies were treated with cholesteryl hemisuccinate or 25-hydroxycholesterol and the subsequent changes in their membrane fluidity and capacity to induce skin reactivity in the homologous patient were investigated. Both cholesterol derivatives were found equally efficient in decreasing membrane fluidity when measured by fluorescence polarization of diphenylhexatriene. Using trimethylammonium-diphenylhexatriene, a specific cell surface probe, 25-hydroxycholesterol, appeared much more efficient than cholesteryl hemisuccinate in inducing a membrane rigidification in the carcinoma cells. Cells treated with cholesteryl hemisuccinate induced a strong positive skin reaction compatible with delayed-type hypersensitivity in 54% of the patients, whereas 25-hydroxycholesterol-treated cells were less potent (36% positive skin reactions). Thus, manipulation of the physicochemical state of the membrane of human renal carcinoma cells could increase their immunogenicity in the autologous patient, although this seemed not to be related only to membrane rigidification. PMID- 2311643 TI - Primary lymphoma of the bladder: a clinicopathological study of 3 cases. AB - Primary involvement of the bladder by lymphoma is rare but is associated with a favourable prognosis if diagnosed early and treated appropriately. The clinicopathological features of 3 cases of primary, non-Hodgkin's lymphoma of the bladder are described. This small study suggests a better prognosis with a favourable histological grade and an uncomplicated lymphoma confined to the bladder. We emphasise the value of aggressive treatment of the tumour. PMID- 2311644 TI - A new HLA-DRB1 allele within the DRw52 supertypic specificity (DRw13-DwHAG): sequencing and direct identification by oligonucleotide typing. AB - Molecular analysis of HLA class II polymorphism represents a crucial parameter for HLA matching in transplantation immunology, for the study of HLA-disease association and for the understanding of major histocompatibility complex (MHC) restricted antigen presentation. We report here the DNA sequence and the deduced amino acid sequence of the polymorphic first domain exon of the DRB1 and DRB3 alleles of the homozygous cell line HAG (DRw13-DwHAG-DQw7). The DRB1 sequence represents a new DRB allele, which clearly shows a close relationship to other DRB1 genes from the DRw52 group and is now officially named DRB1* 1303. The DRB1* 1303 allele is very similar to the two DRw13 alleles we have described earlier, with only five amino acid differences at positions 32, 37, 47, 57 and 71. Furthermore, its sequence in the third hypervariable region is unique among all known DRB1 and DRB3 alleles. The sequence of the DRB3 gene of HAG shows that it corresponds to the previously described DRB3* 0101 (DRw52a) allele. In addition we present analyses of a panel of healthy blood donors and leukemic patients by oligonucleotide typing showing that this new HLA-DR specificity can now be unequivocally identified in routine oligotyping with an allele-specific oligonucleotide probe. PMID- 2311645 TI - Complement activation by immunoglobulin does not depend solely on C1q binding. AB - A matched set of rat chimeric antibodies has been studied for their ability to activate various key stages of the complement cascade. Rat IgM and IgG2b were efficient at all stages from C1q binding to cell lysis. However, for other isotypes, a direct correlation between C1q binding and cell lysis did not apply. IgG2a, which was only modestly efficient at C1q binding, was relatively more so for binding and activation of while C1, and was by far the most effective isotype after IgG2b and IgM for C4 and C3 binding. IgG2c was relatively efficient at binding C1q and C1, but less so for the binding of C4 or for later stages. IgA was efficient at binding C1, but again, this was not reflected in activation of later stages. The results suggest that properties of different isotypes, as well as influencing binding of C1q, may regulate attachment of the C1r2C1s2 tetramer. In addition, distinct features of certain isotypes may favor C4 activation and binding, independent of their ability to activate C1. PMID- 2311646 TI - Differential activity of interleukin 1 alpha and interleukin 1 beta in the stimulation of the immune response in vivo. AB - The biological activities of human recombinant interleukin (IL) 1 alpha and IL 1 beta were compared in different biological systems. The two IL 1 forms were equally active in vitro in inducing proliferation of murine thymocytes and of the murine T helper clone D10.G4.1, and in triggering release of prostaglandin E2 from human skin fibroblasts. In vivo, IL 1 alpha and IL 1 beta were similarly pyrogenic both in rabbits and mice, and could equally increase the circulating levels of the acute phase protein serum amyloid A in mice. However, only IL 1 beta showed immunostimulatory activity in vivo, as it could enhance the number of specific antibody-producing cells in the spleen of mice immunized with either a T dependent or a T-independent antigen. Although devoid of immunostimulatory activity, IL 1 alpha could efficiently compete immunostimulation induced by IL 1 beta, suggesting an effective interaction with the IL 1 receptor. Thus, IL 1 beta appears to have an important role in the positive regulation of immune responses, while IL 1 alpha may act as down-regulator of the IL 1 beta effect. PMID- 2311647 TI - Interleukin 2, 4 and 5 are sequentially produced in mitogen-stimulated murine spleen cell cultures. AB - Lymphokine production was analyzed in murine spleen lymphocytes stimulated with different T cell mitogens. Using in situ hybridization, frequencies of cells and the kinetics of production of interleukin (IL) 2, 4 and 5 were analyzed. The different mitogens varied in their ability to induce the three interleukins. IL2 was most successfully induced with a high dose of the calcium ionophore A23187 combined with phorbol 12-myristate 13-acetate (PMA). Significant frequencies of cells containing IL4 or IL5 mRNA were found among cells stimulated with an anti CD3 antibody together with PMA, or pokeweed mitogen. The combination of anti-CD3 and PMA induced relatively high frequencies of all three cytokines. The production was sequential with the highest levels of IL2 mRNA present during the first 24 h, IL4 mRNA reaching a peak on day 2 and finally IL5 peaking on day 3. When cells that had been stimulated with mitogens in vitro were restimulated, the lymphokines were produced more rapidly. The order of production was maintained with IL2 mRNA reaching a maximum already at 3 h of culture, IL4 mRNA at 8 h and IL5 mRNA at 24 h. PMID- 2311648 TI - Macrophage-secreted prostaglandin E2 potentiates immune complex-induced B cell unresponsiveness. AB - Immune complexes (IC) are potent modulators of immune responses. In this report, we used an in vitro murine model system to investigate how two types of accessory cells pulsed with IC regulated B cell function. We demonstrate that IC-pulsed macrophages (M phi) induce hapten-specific B cell unresponsiveness, whereas IC pulsed splenic lymphoid dendritic cells (LDC) and and LDC-like tumor line caused an augmentation of the antibody response. The mechanism by which IC-pulsed M phi diminished antibody production required two signals. The first was an antigen specific signal supplied by the IC, and the second a nonspecific co-factor which was a product of M phi cyclo-oxygenase metabolism. Specifically, it was shown that prostaglandin E2 (PGE2) could function at this co-factor. Interestingly, other prostanoids, such as PGF2 alpha, did not function in this fashion. Purified fluorescein (FL+)-specific B cells pulsed with IC exhibited a similar pattern of hapten-specific unresponsiveness. Treatment of accessory cell-free, FL+B cells with PGE2 rendered them sensitive to subtolerogenic doses of soluble IC. Overall, our results suggest that one mechanism by which unresponsiveness can be induced involves both IC and PGE2, and that elevated levels of PGE2 sensitize B lymphocytes to antigen-specific tolerogenic signals. PMID- 2311649 TI - Cholera holotoxin and its B subunit enhance Peyer's patch B cell responses induced by orally administered influenza virus: disproportionate cholera toxin enhancement of the IgA B cell response. AB - In these studies we analyzed the adjuvant effect of cholera holotoxin or cholera toxin (CT) B subunit on the B cell response to mucosal antigens. Purified Peyer's patch B cells obtained from mice at varying periods of time after oral administration of inactivated influenza virus, with or without a CT preparation, were stimulated in vitro in the absence or presence of various lymphokines. Responses were measured by an antigen- and isotype-specific ELISPOT assay. In this system cultures containing a combination of lymphokines [interleukin 5 (IL 5), interferon-gamma (IFN-gamma), IL 4] gave comparable responses to those containing T cells from immunized mice or supernatant of concanavalin A stimulated T cells and therefore were assumed to express optimum or near optimum B cell responses. Administration of a CT preparation along with influenza virus increased the number of B cells producing anti-influenza antibodies of both the IgM and IgA isotypes, with the effect on the IgA response at least threefold greater than the effect on the IgM response. These results thus indicate that CT preparations enhance the memory B cells response in Peyer's patches and, in addition, suggest that CT enhances isotype switching. In this antigen-specific B cell system IL 4 augmented responses in cultures containing IL 5 but not IFN gamma; in addition, IL 5 and IFN-gamma acted in an additive fashion. Thus, these findings suggest that the effects of IL 5 and IFN-gamma are at least in part, mediated via different cellular differentiation pathways. PMID- 2311650 TI - Induction of transplantation tolerance by intravenous injection of allogeneic lymphocytes across an H-2 class II mismatch. Different mechanisms operate in tolerization across an H-2 class I vs. H-2 class II disparity. AB - Previously, we have shown that the intravenous (i.v.) injection of allogeneic lymphocytes across an H-2 class I-mutant disparity leads to specific skin allograft tolerance caused by irradiation-sensitive donor T cells, which function as veto cells. In the present study, we show that the i.v. injection of H-2 class II-incompatible spleen cells also results in specific skin allograft tolerance. However, tolerance induction depends on the presence of irradiation-resistant non T cells in the donor cell inoculum. Thus, different mechanisms operate in tolerance induction across an H-2 class I vs. H-2 class II mismatch. I.v. injection of allogeneic spleen cells across an H-2 class I plus class II disparity does not result in skin allograft tolerance. Finally, our data show that transfusion-induced suppression of the delayed-type hypersensitivity response against alloantigens does not correlate with skin allograft tolerance induced by i.v. injected allogeneic lymphocytes. In conclusion, the type of H-2 mismatch between transfusion donor and recipient not only determines the occurrence of allograft tolerance but also the mechanism leading to tolerization. PMID- 2311651 TI - Exit of recirculating lymphocytes from lymph nodes is directed by specific exit signals. AB - During recirculation, lymphocytes leave the peculiar structurally inverted lymph nodes (LN) of pigs via blood vessels instead of via efferent lymphatics, as in sheep and other mammals. This functional difference provided an opportunity to show the existence of signals directing lymphocyte exit from LN. The recirculation of pig peripheral blood lymphocytes was traced through fetal sheep LN and of sheep PBL into and out of unsuckled newborn piglet LN, using the lack of natural antibody or natural killer cell function in these immunologically mature young to compare foreign and homologous lymphocyte behavior. In spite of some 50 million years of evolutionary divergence, the detailed kinetics and route of recirculation of the xenogeneic PBL were essentially the same as those of the host species. Thus determinants guiding the anomalous blood exit from pig LN must involve conserved "exit" signals in a new site and not changes in pig lymphocyte homing receptors. PMID- 2311652 TI - Action of antiepileptic and anaesthetic drugs on Na- and Ca-spikes in mammalian non-myelinated axons. AB - The actions of the antiepileptic drugs phenytoin, carbamazepine and phenobarbitone, and the local anaesthetic drugs lignocaine and procaine on sodium dependent and calcium-dependent compound action potentials (Na- and Ca-spikes) have been compared in rat preganglionic cervical sympathetic nerves, using extracellular recording techniques. There was no discernible difference in the frequency dependence of Na-spike block over the frequency range 0.2-20 Hz between these two groups of drugs. However the antiepileptic drugs were more potent blockers of the Ca-spike, whereas the local anaesthetics were more potent on the Na-spike. It is proposed that a dual action of antiepileptics, a frequency dependent block of sodium currents combined with a block of calcium currents, may explain their efficacy in the treatment of seizures. PMID- 2311653 TI - Trans-cranial electrical stimulation attenuates abrupt morphine withdrawal in rats assayed by remote computerized quantification of multiple motor behavior indices. AB - The goal of the present study was to assess the effects of trans-cranial electrical stimulation on the behavioral signs of the abrupt withdrawal syndrome of rats. However, this goal also necessitated the introduction of an experimental model measuring animal behavior for prolonged periods of time using a computerized animal activity monitoring system to quantify spontaneous motor activities associated with abstinence behavior. Comparable withdrawal severity was obtained by both the activity monitoring system and investigator observation of motor signs of abstinence behavior. Moreover, using this system we demonstrate a time-dependent effect of electrical stimulation in reducing the severity of various indices of motor hyperactivity associated with abrupt morphine withdrawal in rats. PMID- 2311654 TI - Antagonistic properties of four suramin-related compounds at vascular purine P2X receptors in the pithed rat. AB - The dose-response curve for the vasopressor effect of alpha, beta-methylene ATP in pithed rats was influenced by four suramin-related drugs (each at 100 mumol/kg). The curve was shifted to the right by a factor of 8 by 'compound 3' and by a factor of 2 by two other derivatives, but was not affected by the fourth analogue. Compound 3 had no effect on the vasopressor response to noradrenaline or neuropeptide Y. In conclusion, compound 3 is a purine P2X receptor antagonist which is approximately as potent as suramin, and which, like suramin, does not exhibit antagonistic properties at alpha-adrenoceptors and neuropeptide y receptors. PMID- 2311655 TI - Stress activation of limbic and cortical dopamine release is prevented by ICS 205 930 but not by diazepam. AB - Systemic administration of the 5-HT3 receptor antagonist ICS 205-930, but not of the benzodiazepine diazepam, was able to prevent the stimulation of dopamine release in the nucleus accumbens and prefrontal cortex induced by restraint stress. These findings suggest that stress is not simply co-extensive with anxiety and that 5-HT3 receptors could regulate the dopaminergic response to stress. PMID- 2311656 TI - Muscarinic receptors mediating the positive inotropic effect of carbachol in embryonic chick ventricle have a low affinity for pirenzepine. AB - Electrically driven ventricular strips from 3 day old chick embryos were used to investigate the ability of pirenzepine, a muscarinic antagonist that distinguishes between subtypes of muscarinic receptors, to antagonize the positive inotropic effect of carbachol. A low pA2 value was found for pirenzepine (6.40) whereas the pA2 value for atropine was 1000-fold higher (9.36). It can be concluded that the positive inotropic effect of carbachol on this tissue is mediated by muscarinic receptors others than M1-receptors. PMID- 2311657 TI - The alpha-neurotoxin erabutoxin b causes fade at the rat end-plate. AB - d-Tubocurarine and the alpha-neurotoxins from snake venom are antagonists at the nicotinic acetylcholine receptor. It is well established that d-tubocurarine causes fade in neuromuscular transmission during repetitive nerve stimulation but paradoxically there are many reports which indicate that the alpha-neurotoxins do not cause such fade. We found that high concentrations of erabutoxin b (100-150 nM) from the venom of Laticauda semifasciata did not cause much fade in the rat diaphragm preparation. However, low concentrations of toxin (5 nM) caused severe fade which was similar to the effects of d-tubocurarine. The data suggest that fade may be caused by toxin binding to a high-affinity site on the postsynaptic acetylcholine receptor. PMID- 2311658 TI - The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat. AB - The effects of the selective CCK-A antagonist L-365,031 and the selective CCK-B antagonist L-365,260 on morphine analgesia and opiate tolerance and dependence in rats were examined. L-365,031 and L-365,260 had no effect on baseline pain thresholds in the radiant heat tail flick test but enhanced analgesia induced by a submaximal dose of morphine (4 mg/kg). Similarly, L-365,260 did not effect pain thresholds in the paw pressure test but enhanced morphine analgesia in this model. Rats injected twice daily for 6 days with incremental doses of morphine became tolerant to the analgesic effects of the drug. Twice daily injections of either 8 mg/kg L-365,031 or 0.2 mg/kg L-365,260 prevented the development of tolerance to morphine analgesia. In contrast, L-365,260 had no influence on the development of opiate dependence in these animals, as assessed by naloxone precipitated withdrawal. The results of the present study, when considered together with previous data, indicate that the rank order of potency of non peptide CCK antagonists for enhancing morphine analgesia is L-365,260 greater than MK-329 greater than L-365,031. This rank order correlates well with the potency of the antagonists in blocking CCK-B receptors in rodents and suggests that CCK/opiate interactions in this species are mediated by CCK-B receptors. PMID- 2311659 TI - Tolerance develops to spinal morphine analgesia but not morphine-induced convulsions. AB - Administration of morphine into the spinal intrathecal (i.t.) space produced dose dependent analgesia in the mouse. At higher doses i.t. morphine induced seizures of the hindlimbs. Mice treated chronically with morphine (75 mg pellet, s.c.) for 72 h were tolerant to the analgesic effects of i.t. morphine, but not to the proconvulsant action. Spinal morphine analgesia was attenuated by naloxone, whereas i.t. morphine-induced seizures were not. These results indicate that spinal opioid receptors mediate analgesia but not seizures following i.t. morphine treatment in the mouse. PMID- 2311660 TI - Amitriptyline-induced morphological alterations of the rat blood-brain barrier. AB - Amitriptyline is known to increase the permeability of the blood-brain barrier but the morphological basis of this increase has not been studied. As catecholamines can influence pinocytosis in dog peripheral blood vessels, the effect of amitriptyline on the pinocytotic activity of blood brain microvessels was studied. Amitriptyline, 34 mg.kg-1 i.p., was injected to rats and the parietal cortex of control and treated animals was prepared for ultrastructural study. Pinocytotic vesicles in endothelial cells were quantified. Amitriptyline significantly increased the density of pinocytotic vesicles in capillary endothelial cells. No other morphological changes occurred after amitriptyline treatment. We conclude that the increase in blood-brain barrier permeability due to amitriptyline may be ascribed at least in part to an increase of pinocytotic activity in brain capillary endothelial cells. PMID- 2311661 TI - Effects of calcium channel inhibitors upon the efficacy of common antiepileptic drugs. AB - Diltiazem and nifedipine (both 1.25 mg/kg) markedly potentiated the protective action of carbamazepine and diphenylhydantoin against maximal electroshock induced seizures in mice. These calcium channel inhibitors retained their activity at lower doses. Diltiazem and nifedipine (2.5 mg/kg) also moderately potentiated the efficacy of phenobarbital and valproate. Verapamil (up to 10 mg/kg) was not effective against the action carbamazepine, diphenylhydantoin, phenobarbital, and valproate. None of the calcium channel inhibitors used (up to 40 mg/kg) influenced aminophylline-induced convulsions and mortality. Moreover, the anti-aminophylline activity of valproate and phenobarbital was not potentiated by the calcium channel inhibitors in doses up to 10 mg/kg. Further, combination of carbamazepine, ethosuximide, and trimethadione with the calcium channel inhibitors (up to 10 mg/kg) did not offer any protection against aminophylline-induced convulsions. It can be concluded that calcium channel inhibitors enhance the protective efficacy of some antiepileptics against electroconvulsions. A pharmacokinetic interaction does not seem to be responsible for this effect. PMID- 2311662 TI - Effects of adenosine on adrenergically induced renal vasoconstriction in dogs. AB - The role of exogenous and endogenous adenosine in the neural control of renal blood flow was studied in anesthetized dogs. The plasma norepinephrine (NE) concentration was measured by high-performance liquid chromatography and the renal NE secretion rate was calculated. Renal nerve stimulation (1-3 Hz) reduced renal blood flow and increased NE secretion rate. The intrarenal arterial injection of NE (0.3-1.0 micrograms) also reduced renal blood flow. Infusion of adenosine (10-100 micrograms/min) into the renal artery attenuated the increase in NE secretion rate induced by renal nerve stimulation, but the nerve stimulation-induced decrease in renal blood flow was unaffected. On the other hand, adenosine potentiated the NE-induced renal blood flow response. Similar results were obtained with an adenosine potentiator, dipyridamole (1-10 micrograms/min). An adenosine receptor blocker, theophylline (0.3-1.0 mg/min), potentiated the NE secretion rate response induced by nerve stimulation, without any change in the renal blood flow response. The NE-induced renal blood flow response was attenuated by theophylline. These results suggest that adenosine inhibits neural NE release and enhances vasoconstriction in the dog kidney during sympathetic stimulation under in vivo conditions. These post- and presynaptic mechanisms may thus be activated by endogenous adenosine. PMID- 2311664 TI - Characteristics and localisation of 125I ion binding in mammalian airways. AB - We have examined some of the binding characteristics and the autoradiographic distribution of binding sites for Na125I (I-Na) in airway tissue from the guinea pig, monkey, pig, rat, mouse and from man. Basal I-Na (100 pM) binding levels were extremely low. However, in the presence of ascorbic acid (10 microM) or dithiothreitol (10 microM), I-Na binding was markedly increased in guinea-pig trachea, with lesser increases detected in monkey and rat trachea and in monkey and human bronchus. In guinea-pig trachea, ascorbic acid-induced I-Na binding was not saturable within the concentration range 100-620 pM and could not be reduced by washout. Autoradiography revealed that in central airways, I-Na binding was localized at or near the interface of the airway epithelium and submucosa in small clusters, apparently involving one or two cells per focus. The physiological significance of these binding sites is yet to be established, although they may be involved in intracellular iodine storage. PMID- 2311663 TI - Neuropeptide Y potentiates purinergic as well as adrenergic responses of the rabbit ear artery. AB - The localisation of neuropeptide Y in the rabbit central ear artery and its pharmacological action on this preparation were investigated. Immunohistochemical studies demonstrated the presence of neuropeptide Y-like immunoreactivity in the perivascular nerves supplying the rabbit ear artery. Forty-eight hours after treatment with reserpine (5 mg/kg i.p. 48 h and 3 mg/kg i.p. 24 h prior to the experiment) catecholamine fluorescence in the rabbit central ear artery was abolished and the neuropeptide Y-like immunoreactivity was substantially reduced, suggesting that noradrenaline and neuropeptide Y were colocalised in sympathetic nerves. Contractile responses to exogenous noradrenaline (1 microM) and alpha,beta-methylene ATP (1 microM) were both significantly potentiated following incubation with neuropeptide Y (0.3 microM); the degree of potentiation being similar for both agonists. Electrical field stimulation of the rabbit central ear artery (16 and 64 Hz) produced frequency-dependent contractile responses which were abolished by tetrodotoxin (1 microM) and which were significantly potentiated in the presence of neuropeptide Y (0.3 microM). The responses to stimulation at 16 Hz were enhanced to a greater extent than the responses at 64 Hz. After blocking the noradrenergic component of the neurogenic response with prazosin (1 microM), the residual purinergic component, at both 16 and 64 Hz, was significantly enhanced in the presence of neuropeptide Y. However, following desensitisation of the P2-purinoceptor with alpha,beta-methylene ATP, neuropeptide Y had no significant effect on the residual noradrenergic component.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311665 TI - Effect of dantrolene sodium in isolated guinea-pig trachea. AB - The effect of dantrolene sodium (3 microM-0.3 mM) on the spontaneous tone and responses to various contractile agonists was studied in isolated guinea-pig trachea. Dantrolene produced a concentration-related inhibition of the spontaneous tracheal tone, reaching a value of 94.8 +/- 4.8% of the relaxation induced by caffeine 10 mM. Removal of the epithelium did not affect the dantrolene-induced relaxation. Dantrolene did not alter the concentration response curve for KCl and produced only small displacements of the concentration response curves for CaCl2, acetylcholine and histamine, without affecting their maximal effects. Dantrolene dose relatedly inhibited the contraction induced by caffeine (1 mM) in Krebs solution containing indomethacin (2.8 microM) at 20 degrees C. The spasm induced by caffeine in Ca2(+)-free Krebs solution (20 degrees C, indomethacin 2.8 microM) was slightly depressed by dantrolene. Dantrolene did not depress the Ca2+ (1 microM)-induced contraction in skinned trachea. These results suggest that besides a possible intracellular site of action, the mechanism of the inhibitory effect of dantrolene in guinea-pig trachea may be related to interference with Ca2+ entry through pathways not susceptible to calcium channel blockers. PMID- 2311667 TI - The binding of [3H]4-diphenylacetoxy-N-methylpiperidine methiodide to longitudinal ileal smooth muscle muscarinic receptors. AB - Muscarinic receptors present in longitudinal ileum were characterized using the non-selective radioligand [3H]N-methylscopolamine [( 3H]NMS) and the M3 selective radioligand [3H]4-diphenylacetoxy-N-methylpiperidine methiodide [( 3H]4DAMP). In saturation studies, [3H]4DAMP, but not [3H]NMS, identified two populations of binding sites with 17% of the sites (155 fmol/mg protein) displaying high affinity (Kd = 0.39 nM) for [3H]4DAMP and the remaining sites displaying low affinity for the radioligand (Kd = 4.43 nM). In competition studies gallamine and methoctramine, but not AF-DX 116, identified two populations of [3H]NMS binding sites. Affinity estimates for gallamine and methoctramine indicated that 80% of the [3H]NMS binding sites were of the M2 subtype. The minor population of [3H]NMS binding sites could not be readily characterized, due partly to the low selectivity of the competing ligands and also to the relatively low density of the sites. In studies using the M3 muscarinic receptor selective radioligand [3H]4DAMP, the minor population of sites could be preferentially labeled by using a low concentration (0.4 nM) of [3H]4DAMP. Under these conditions, [3H]4DAMP labeled approximately equal levels of the two muscarinic receptor binding sites present in the ileum. Competition studies with AF-DX 116, gallamine and methoctramine indicated that the two [3H]4DAMP binding sites displayed the pharmacology expected of the M2 and M3 receptors, respectively. These results provide additional evidence that longitudinal ileal smooth muscle membranes contain both M2 and M3 muscarinic receptors and indicate that [3H]4DAMP is a useful ligand for identifying heterogeneity of muscarinic receptor subtypes. PMID- 2311666 TI - Role of intragastric pH in cytoprotection by antacids in rats. AB - Antacids containing Al(OH)3 have been shown to stimulate the protective and reparative processes in the gastric mucosa exposed to various ulcerogens but the mechanisms of these effects are unknown. This study was designed to determine the role of intragastric pH and mucosal formation of prostaglandins (PG) in antacid induced protection of gastric mucosa against ethanol or aspirin damage. Maalox 70 and its active component, Al(OH)3, were used alone at the original pH (7.5 and 6.0, respectively) and lower pH or were combined with ranitidine or histamine before intragastric administration of 100% ethanol or acidified aspirin to induce acute mucosal lesions. Maalox and Al(OH)3 were relatively more effective to protect against the damage due to ethanol, and to some extent also due to aspirin, when given at a pH (pH 2) lower than at their original pH. Pretreatment with ranitidine, which itself did not change ethanol-induced damage, greatly reduced the protection afforded by Maalox or Al(OH)3, whereas pretreatment with histamine enhanced this protection. Maalox and Al(OH)3 at their original or low pH did not alter significantly the capability of gastric mucosa to generate PG but resulted in a significant increase in luminal release of PG. Pretreatment with indomethacin to reduce mucosal generation of PG failed to affect the protective effects of Maalox or Al(OH)3 at their original or lower pH. We conclude that Maalox 70 and Al(OH)3 protect the gastric mucosa against ethanol damage but that this protection requires the presence of acid and may not depend entirely upon the mucosal production of PG. PMID- 2311668 TI - Stress increases noradrenaline release in the rat frontal cortex: prevention by diazepam. AB - Foot-shock produced a more than 2-fold increase in noradrenaline (NA) release from the frontal cortex of freely moving rats. The effect of acute stress was almost completely prevented by the administration of diazepam (5 mg/kg i.p.). Diazepam alone inhibited cortical NA release, the maximal inhibition (-57%) being observed 90 min after the injection. Cortical NA release therefore appears to be a reliable index of central noradrenergic activity in response to stressful conditions. PMID- 2311669 TI - Local cutaneous hemodynamic effects of carvedilol and labetalol in the anesthetized rat. AB - The effects of labetalol and carvedilol and local cutaneous microvascular perfusion and calculated local cutaneous microvascular resistance were investigated in anesthetized rats at submaximal doses that produced equivalent reductions in blood pressure and heart rate. Labetalol decreased cutaneous perfusion (-25 +/- 3%) without significantly affecting cutaneous vascular resistance (-6 +/- 3%). In marked contrast, carvedilol dramatically increased cutaneous perfusion (+64 +/- 9%) and significantly reduced cutaneous vascular resistance (-57 +/- 3%). These results suggest that carvedilol and labetalol possess differences in the mechanisms by which they produce vasodilation in vivo. PMID- 2311670 TI - Nimodipine inhibits cocaine-induced dopamine release and motor stimulation. PMID- 2311672 TI - The generation of L-arginine in endothelial cells is linked to the release of endothelium-derived relaxing factor. PMID- 2311671 TI - Complex interaction of cocaine with the dopamine uptake carrier. PMID- 2311673 TI - Reproducible vasodilatation by platelet-activating factor in blood- and Krebs perfused rat kidneys is albumin-dependent. AB - The vasodilator effect of platelet-activating factor (PAF) and its reproducibility was determined in rat kidneys perfused in situ with blood or in isolated kidneys perfused with Krebs solution or Krebs plus 0.25% bovine serum albumin (BSA) at 3 ml/min. Dilatation was measured as inhibition of the increase in perfusion pressure produced by stimulation of the renal nerves or by infusion of noradrenaline. PAF, in saline and 0.25% BSA, was infused into the perfusate at 0.05 ml/min to produce eight incremental consecutive concentrations from 3 x 10( 11) to 10(-7). Two sets of PAF infusions were made during nerve-stimulated responses followed by one set during noradrenaline infusion. With blood perfusion, PAF consistently produced dose-dependent dilatation and 3 x 10(-9) M reduced nerve-stimulated responses to 52% of control. This effect was reproduced by a second infusion. However in Krebs-perfused kidneys the effect of the first PAF infusion was not consistent, with responses either not affected or reduced only at the lower doses so that the mean maximum decrease was only 10% and the vasodilatation was not dose-dependent. The second PAF infusion invariably had no effect. On the other hand perfusion with Krebs and 0.25% BSA produced consistent and dose-dependent inhibition of vasoconstriction which was reproduced by a second infusion. PAF was effective at 10-fold lower doses in Krebs-albumin perfused compared to blood-perfused kidneys. These results indicate that exogenous PAF is a potent and reproducible dilator of the rat renal vasculature perfused with blood or Krebs-albumin solution but not albumin-free Krebs solution. PMID- 2311674 TI - Characterization of the analgesic activity of ketorolac in mice. AB - The spectrum of analgesic activity of ketorolac tromethamine was evaluated with mice exposed to the hot-plate, tail-flick and writhing tests. Morphine and indomethacin were used as representative opioid and non-steroidal analgesics respectively. Ketorolac in doses of 5 or 7.5 mg/kg i.p. was active as an analgesic in all three of the procedures. In each case, naloxone (0.5 mg/kg i.p.) significantly decreased the analgesic activity of ketorolac. It was suggested that ketorolac might act in part by causing the release of endogenous opioids. PMID- 2311675 TI - Antidepressant-like effects of trazodone on a behavioral screen are mediated by trazodone, not the metabolite m-chlorophenylpiperazine. AB - Trazodone is an atypical antidepressant drug (i.e. blocks neither monoamine uptake nor monoamine oxidase) which tests as an antidepressant drug on the differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement by increasing the reinforcement rate and decreasing the response rate. m Chlorophenylpiperazine (m-CPP) is a 5-HT1B and 5-HT1C agonist, weak 5-HT2 antagonist, and trazodone metabolite. It has been suggested that formation of m CPP is responsible for the antidepressant action of trazodone. Administration of m-CPP (1-10 mg/kg i.p.) 60, 30 or 10 min before the behavioral session did not mimic the reinforcement rate-increasing effects of trazodone (10-20 mg/kg i.p.) on rats performing under the DRL 72-s schedule of water reinforcement. Pretreatment with proadifen (50 mg/kg i.p.), an inhibitor of trazodone metabolism, caused a greater than 30-fold leftward shift in the dose-response curve for both the reinforcement rate and the response rate. These results suggest that the parent compound and not the trazodone metabolite m-CPP, mediates the antidepressant-like effects of trazodone on DRL 72-s behavior. PMID- 2311676 TI - Endogenous aspartate release in the rat hippocampus is inhibited by M2 'cardiac' muscarinic receptors. AB - The release of endogenous aspartic acid elicited by depolarization of rat hippocampus synaptosomes with 15 mM KCl was totally calcium-dependent. Acetylcholine (ACh) added to the superfusion medium inhibited the K(+)-evoked release of aspartate in a concentration-dependent manner. The effect of ACh was mimicked by oxotremorine and carbachol. It was insensitive to the nicotinic receptor antagonist mecamylamine but blocked by the non-selective muscarinic receptor antagonist atropine. Further pharmacological characterization of the muscarinic receptor involved showed that the ACh effects was insensitive to the M1 selective muscarinic receptor antagonists pirenzepine and dicyclomine. However, the inhibition by ACh of aspartate release was counteracted by 11-[[2 [(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido-[2-3 b][1,4]benzodiazepine-6-one (AF-DX 116), a selective M2 'cardiac' receptor antagonist. The calcium dependence of the release of aspartate and its regulation through presynaptic receptors are suggestive of a transmitter role for this excitatory amino acid. Moreover, the similarities between the present results and those previously obtained with glutamate are compatible with the idea that aspartate and glutamate are co-released in the rat hippocampus. PMID- 2311677 TI - Inhibition by indomethacin of the increased facility of outflow induced by adrenaline. AB - Topical adrenaline lowers intraocular pressure (IOP) in the rabbit largely due to an increase in facility of outflow of aqueous humour. This paper studies the inhibition by indomethacin or piroxicam of the adrenaline-induced rise in facility of outflow. Topical indomethacin is shown to reduce the acute IOP changes induced by adrenaline in conscious rabbits; both the early rise and the prolonged fall in pressure were inhibited. In anaesthetized rabbits, indomethacin pretreatment prevented the large rise in facility of outflow which normally follows topical adrenaline. Indomethacin did not block the mydriasis induced by adrenaline, nor did it significantly alter aqueous humour protein levels. Piroxicam, a cyclo-oxygenase inhibitor which, unlike indomethacin, does not block Ca2+ movements in some tissues, also blocked the adrenaline-induced rise in facility of outflow, suggesting that this increased facility depends on cyclo oxygenase and not on Ca2+ movements. Verapamil, a drug which blocks Ca2+ channels, was shown to inhibit the brief ocular hypertensive effect of adrenaline in the conscious rabbit, but to leave the hypotensive phase unchanged. It is concluded that the hypotensive mechanism of adrenaline may depend on synthesis of a prostaglandin, since inhibition of the adrenaline-induced rise in facility is achieved by inhibitors of cyclooxygenase. Despite previous reports that a prostaglandin may be responsible for the brief hypertensive phase, the present evidence suggests that Ca2+ movements may be involved, perhaps in activation of the extraocular muscles. PMID- 2311678 TI - Serine hydroxymethyltransferase: evidence for its presence in human, monkey and rat lenses. AB - Serine hydroxymethyltransferase (SHMT) is present in cultured rat, monkey and human lenses as shown by 15N-serine or 15N-glycine labeling studies. Following incubation with 15N-serine, the percent enrichment of 15N in glycine increases with time, and vice versa, demonstrating the presence of the enzyme, and the reversibility of the reaction in intact cultured lenses. Similar patterns of 15N enrichment were found in all three species, but lenses from young rats showed a higher percent enrichment than lenses obtained from older animals. Label from 15N serine or 15N-glycine was also incorporated into a number of other amino acids, including aspartate, alanine, glutamate and proline. Conclusive evidence for the presence of SHMT in rat lens homogenates has been obtained by direct enzyme assay. The specific activity of rat lens SHMT was age dependent; approximately 2.4 units per mg protein in day old rats, declining to about 0.15 units per mg in adult animals. The higher specific activity observed in younger animals is consistent with the 15N labeling results obtained with cultured lenses. Lens SHMT has been partially characterized. In the presence of excess tetrahydrofolate the assay was essentially linear with increasing time. With serine as the substrate, the enzyme requires tetrahydrofolate for activity, the pH optimum is between pH 7.5 and 8.3, the Km for serine is about 0.25 mM, and the enzyme is inhibited by cycloserine. In conclusion, this study demonstrates the existence of SHMT in rat, monkey and human lenses. Rat lens specific activity has been shown to decrease with increasing age, and the enzyme has been partially characterized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311679 TI - Ibuprofen, a putative anti-cataract drug, protects the lens against cyanate and galactose. AB - Cataract, the major cause of blindness world-wide, may be caused partly by modification of lens proteins by carbamylation and non-enzymic glycosylation (glycation) in some patients. Aspirin has been found to protect against these modifications and to prevent cyanate-induced opacification occurring in whole rate lenses. Ibuprofen is an aspirin-like anti-inflammatory drug which appeared as a protective factor against cataract in an Oxford case-control study. The binding of cyanate, galactose and glucose 6-phosphate to lens proteins, and the effect of ibuprofen on this reaction was investigated, as was cyanate-induced opacification in whole rat lenses. Labelled metabolite was incubated with bovine lens homogenate in the presence and absence of ibuprofen, and the incorporation of label into the lens homogenate was followed. Simultaneous and preincubation experiments were performed. Intact rat lenses were incubated in culture medium with and without cyanate and ibuprofen. The phase separation temperature was noted as the temperature at which opacity first appeared on cooling. Cyanate, galactose and glucose 6-phosphate bind progressively to lens proteins. Simultaneous incubation with ibuprofen reduces cyanate and galactose binding but not glucose 6-phosphate. Ibuprofen protects against opacities due to cyanate induced phase separation. Ibuprofen has protected against cataract in the models of cataractogenesis in this study. It appears to have a different mechanism of action from that of aspirin. These studies provide some support for the idea, based on epidemiological findings, that ibuprofen might be a useful anti-cataract drug. PMID- 2311680 TI - Effect of a novel soft steroid on the wound healing of rabbit cornea. AB - The effect of a 'soft' anti-inflammatory corticosteroid on the corneal wound healing was investigated in rabbits. Albino rabbits were treated with soft steroid and dexamethasone after linear perforating corneal incision. Soft drug design is aimed to control and direct the drug activity and in vivo metabolism to nontoxic moieties. These drugs are rapidly deactivated after they reach the general circulation. While having good local activity, they thus possess high therapeutic indexes without systemic side effects. The wound healing process was evaluated qualitatively by histology. Photomicrographs are presented to show that the soft steroid is as or more effective than dexamethasone in minimizing scarring in addition to its advantageous metabolic properties. This soft steroid may be an efficient anti-inflammatory and anti-allergic agent in topical application without the majority of unwanted activities of traditional drugs by deliberately simplifying their disposition. PMID- 2311681 TI - Modulation of the blood-aqueous barrier by gram positive and gram negative bacterial cell wall components in the rat and rabbit. AB - Acute anterior uveitis in man is related to Gram negative bacterial infection occurring at sites distant to the eye. This could involve intraocular localization of inflammatory bacterial cell wall constituents. Modulation of the blood-aqueous barrier in rabbit and rat, by muramyl dipeptide (the monomer of peptidoglycan) and lipopolysaccharide (and its monomer lipid A) was studied. The rabbit eye was found to be highly susceptible to MDP and LPS, although without cellular infiltration. In contrast the rat eye was demonstrated to be totally refractory to MDP. The response to LPS in the rat was modest, required high dosages and ocular changes were slow to occur, but cellular infiltration was readily apparent. Since MDP is found in Gram positive (as well as Gram negative) bacterial cell walls it is hypothesized that Gram positive bacteria might also play a role in causing uveitis in man. PMID- 2311682 TI - Age-related changes in fibre differentiation of rat lens epithelial explants exposed to fibroblast growth factor. AB - Epithelial cells explanted from neonatal rat lenses undergo changes characteristic of fibre differentiation when cultured with neural retina, neural retina-conditioned medium (RCM), or acidic and basic fibroblast growth factor (FGF). In neonates fibre differentiation is marked by cell elongation, the accumulation of alpha-crystallin, and the appearance of beta- and gamma crystallins. To analyze the fibre differentiation response of lens epithelial cells in later life, we compared the fibre differentiation responses of lens epithelia from 3-, 10- and 21-day- 14-week-, and 6-month-old rats to basic fibroblast growth factor (bFGF). Explants of the central epithelium were used to maintain consistency between ages. Crystallin composition of explants was analyzed by immunofluorescence and ELISA methods. Only explants from 3-day-old rats demonstrated any ability to synthesize gamma-crystallin in response to bFGF. Central lens epithelia explanted from rats up to 14 weeks old accumulated alpha- and beta-crystallins when exposed to bFGF. The onset of crystallin accumulation, however, was increasingly delayed, and the amount of crystallin accumulated by the end of the culture period declined as the age of the donor rat increased. The diminished ability of lens epithelial explants from older rats to undergo fibre specific changes in response to bFGF is also demonstrated in the reduced degree of morphological changes characteristic of fibre differentiation. Cell elongation and multilayering in response to bFGF was observed in explants from 3-day-old rats but was substantially reduced in explants from 14-week-old rats. Explants from 6-month-old rats failed to demonstrate any evidence of morphological change or crystallin accumulation in response to bFGF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311683 TI - Evidence that the gluconeogenic pathway is confined to an enriched Muller cell fraction derived from the amphibian retina. AB - An enriched Muller cell fraction was prepared from bullfrog retina, employing the endoprotease bromelain to digest the retina, and iso-osmotic Percoll gradient centrifugation to resolve the retinal digest. The Muller cell was the most resistant of all retinal cells to bromelain digestion, thus large numbers of morphologically intact cells were produced. The only other retinal cells that survived bromelain digestion were cones and some bipolar cells. The enriched Muller cells were incubated in 10 mm lactate Ringer containing U-[14C]lactate and the amount of [14C]glucose synthesized was used as the biochemical endpoint for assessing the rate of gluconeogenesis. There was no incorporation of [14C]glucose into Muller cell glycogen: however, 2.8 nmol glucose (mg Muller cell protein x hr)-1 was released to the medium. The synthesis and release of glucose to the medium was increased four- to sixfold by glucagon, vasoactive intestinal peptide or a mixture of forskolin/IBMX. In addition, glycolytic flux of isolated intact retina was determined with 3-[3H]glucose. In lactate-free and lactate-containing Ringer, glycolytic flux was 92.5 and 67.9 nmol (mg protein x hr)-1, respectively. In the presence of 100 nM vasoactive intestinal peptide, glycolytic flux in lactate-free and lactate-containing Ringer was reduced by 50 and 66%, respectively. These data strongly suggest that a Cori-like cycle exists in the amphibian retina and the Muller cell may be the predominant site for the gluconeogenic pathway. In addition, vasoactive intestinal peptide may serve both as a gluconeogenic and antiglycolytic neurohormone in the amphibian retina. PMID- 2311684 TI - Distribution pattern of native fluorophores in cataractous lenses. PMID- 2311685 TI - Shedding of cone photoreceptor disk membranes in lizard eyecups maintained in vitro. PMID- 2311687 TI - The lateral reticular nucleus in the cat. VI. Excitatory and inhibitory afferent paths. AB - The afferent paths from the spinal cord and from trigeminal afferents to the lateral reticular nucleus (LRN) were investigated by intracellular recording from 204 LRN neurones in preparations with a spinal cord lesion at C3 that spared only the ipsilateral ventral quadrant. Stimulation of nerves in the limbs evoked EPSPs and JPSPs in 201 of 204 tested LRN neurones. The strongest input was from the ipsilateral forelimb (iF) which evoked EPSPs in 49% and IPSPs in 73% of the LRN neurones. Each of the other limbs evoked EPSPs in approximately 20% and IPSPs in approximately 25% of the neurones. Stimulation of the ipsilateral trigeminal nerve (iTrig) evoked EPSPs in 32% and IPSPs in 46% of the neurones. The shortest latencies of the EPSPs and IPSPs indicated a disynaptic connection between primary afferents in the iF and iTrig and the LRN. The most direct pathways for excitatory and inhibitory responses from the other limbs were trisynaptic. Stimulation of the ventral part of the ipsilateral funiculus (iVLF) at C3 (C3iVLF) evoked monosynaptic responses in 189 of 201 tested LRN neurones. Monosynaptic EPSPs were recorded in 104 neurones and monosynaptic IPSPs in 126 neurones. Monosynaptic EPSPs and IPSPs were encountered in all parts of the LRN. Stimulation of the iVLF at L1 (L1iVLF) evoked monosynaptic EPSPs and IPSPs in the ventrolateral part of the LRN. The termination areas of excitatory and inhibitory fibres appeared to be the same. LRN neurones without monosynaptic EPSPs or IPSPs from the L1iVLF were located mainly in the dorsal part of the magnocellular division. Stimulation of the dorsal funiculi (DF) at C2 and the ipsilateral trigeminal nerve (iTrig) evoked excitatory and inhibitory responses in the LRN. The shortest latencies of EPSPs and IPSPs indicated disynaptic connections. PMID- 2311686 TI - Gating of tactile input from the hand. II. Effects of remote movements and anaesthesia. AB - Tactile sensations of flutter or pressure were evoked in alert human subjects by intraneural microstimulation in the median nerve. Ratings were obtained of the magnitude of sensations at threshold for conscious detection during movement of the finger to which they were projected, of neighbouring fingers or of the opposite hand. Results showed that inhibition of flutter sensation was maximal in the moved finger (48%), with a weaker graded effect from adjacent (23%) to distant (19%) fingers of the same hand. Sensations of pressure were more markedly suppressed but the gradients were similar. Movement of the opposite hand and isometric contraction of the forearm muscles had little effect. Local anaesthetic blocks of the median and other upper limb nerves counteracted most of the inhibitory effect of movement on cutaneous flutter sensation. We conclude that sensory gating is largely restricted to the moved digits, that it applies to submodalities of both flutter and pressure and that sensory gating is mostly mediated by cutaneous receptor input from the hand. PMID- 2311688 TI - The lateral reticular nucleus in the cat. VII. Excitatory and inhibitory projection from the ipsilateral forelimb tract (iF tract). AB - Intracellular recording from neurones in the lateral reticular nucleus (LRN) demonstrated that, in addition to the previously identified excitatory ipsilateral forelimb tract (iF tract) (Clendenin et al. 1974c) there is an inhibitory tract mediating information from the ipsilateral forelimb to the LRN. The excitatory and inhibitory tracts were similarly organized. The tract neurones were monosynaptically activated by afferents in the ipsilateral forelimb and projected to the same area of the LRN. They will be considered as excitatory and inhibitory components of the iF tract and denoted the excitatory and inhibitory iF tract (EiF and IiF tracts). Stimulation of the descending ipsilateral dorsolateral funiculus (iDLF) in the C3 segment evoked disynaptic EPSPs and IPSPs in LRN neurones contacted by the EiF and IiF tracts. The responses in individual LRN neurones evoked from the iDLF were similar to the responses evoked from the forelimb nerves suggesting that the EiF and IiF tracts are monosynaptically activated by fibres in the iDLF. The dorsal portion of the magnocellular part of the LRN constituted the main termination area of both the EiF and IiF tracts. Neurones in this area have previously been shown to project ipsilaterally to lobule V in the pars intermedia of the cerebellar anterior lobe and to the paramedian lobule (Clendenin et al. 1974a). IPSPs evoked from the IiF tract in LRN neurones outside the main termination area had smaller amplitudes and longer latencies. This finding suggests that these responses were generated by thin axon collaterals given off from dorsally located stem axons. PMID- 2311689 TI - The lateral reticular nucleus in the cat. VIII. Excitatory and inhibitory projection from the bilateral ventral flexor reflex tract (bVFRT). AB - Intracellular recordings were obtained from 204 neurones in the lateral reticular nucleus (LRN). LRN neurones contacted by the bVFRT were identified by the responses evoked on stimulation of descending fibres in the contralateral ventral quadrant of the spinal cord (cVQ) at cervical (C5cVQ) and lumbar (L2cVQ) levels. Stimulation of the cVQ evoked excitatory or inhibitory responses in 124 of the 204 LRN neurones. EPSPs were evoked in 45, IPSPs in 52 and both EPSPs and IPSPs in 27 LRN neurones. The shortest latencies of the responses evoked from the cVQ indicated that both EPSPs and IPSPs were disynaptic. This finding was confirmed by direct stimulation of the ascending fibres in the ipsilateral ventrolateral funiculus at C3 (C3iVLF) or L1 (L1iVLF). In most LRN neurones activated or inhibited from the cVQ, stimulation of the iVLF evoked similar responses at a monosynaptic latency. These results indicate that the bVFRT consists of roughly equally large groups of excitatory and inhibitory neurones monosynaptically connected with the LRN. Excitatory and inhibitory bVFRT neurones had similar peripheral receptive fields and termination areas in the LRN. LRN neurones were divided into those contacted by cervical bVFRT neurones and lumbar bVFRT neurones. The former group consisted of LRN neurones responding to C5cVQ stimulation at latencies below 5 ms, whereas the latter group contained LRN neurones responding to stimulation of the L2cVQ. Cervical bVFRT neurones projected to most parts of the LRN whereas the projection of lumbar bVFRT neurones were confined to the ventrolateral part of the nucleus. Excitatory and inhibitory vVFRT neurones of each group had similar termination areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311690 TI - Differences in central control of m. biceps brachii in movement tasks and force tasks. AB - Motor-unit activity in m. biceps brachii during isometric flexion contractions has been compared with motor-unit activity during a) slow voluntary movements against constant or increasing preloads and b) flexion contractions while movements were imposed by a torque motor. Recruitment levels and firing frequency behaviour of the motor units were found to be very similar when torques were generated during isometric contractions and during the imposed movements. However, these characteristics of the biceps motor units were quite different during the slow voluntary movements. It is suggested that the central activation of the alpha and/or gamma motoneurone pools of m. biceps brachii is different for force tasks and slow movement tasks, even if the same torques are exerted and/or movements are made. PMID- 2311691 TI - A perceptual analysis of stiffness. AB - The perception of stiffness was studied in ten human subject using two servo controlled electromagnetic linear motors with computer-controlled stiffness, one motor coupled to each wrist of the subject. Using the contralateral limb-matching procedure in which subjects adjusted the stiffness of the motor connected to one (matching) arm until it was perceived to be the same as that connected to the other (reference) arm, a psychophysical function for stiffness was calculated. Eight different stiffness intensities were matched by subjects with five repetitions at each stimulus amplitude. The relation between the stiffness of the reference and matching motors was linear, and the accuracy with which subjects could match stiffness paralleled that reported previously for force and displacement. The Weber fraction for stiffness was 0.23 which is three times that reported for elbow flexion forces and forearm displacement. These findings were interpreted as indicating that subjects can perceive changes in the stiffness of mechanical devices used to effect action in the environment and that these perceptions are based on sensory signals conveying force and movement information. PMID- 2311692 TI - Development in the absence of spontaneous bioelectric activity results in increased stereotyped burst firing in cultures of dissociated cerebral cortex. AB - Quantitative analysis of neuronal firing patterns was used to study the effects of chronic suppression of bioelectric activity (BEA) on functional development in primary cultures of fetal rat cerebral cortex. BEA was monitored with extracellular electrodes in active control cultures or, after return to control medium, in cultures chronically silenced with tetrodotoxin (TTX) at around 7, 14, 21 and 42 days in vitro. Spike trains of single neurons lasting up to 25 min duration were analyzed using a previously published set of computer programs. In control cultures, the main developmental trends seen in a previous study could be replicated. After development in the presence of TTX, activity levels were increased at all ages, and a high incidence was found of a single firing pattern characterized by stereotyped burst firing, while showing a low minute order variability in firing rate and low dependencies between successive intervals; conversely, the incidence of variable/non-burst firing was decreased relative to untreated cultures. The former firing pattern (i.e. non-variable bursting) could also be produced through acute addition of the GABA (A)-antagonist picrotoxin to control cultures, and resembled interictal burst firing observed in models of chronic epilepsy in vivo. These similarities suggest that chronic silencing of the cultures may have resulted in a functional disinhibition of the neuronal network; such disinhibition might be related to the increased cell death which we observed with chronic TTX-treatment in the same cultures. PMID- 2311693 TI - Postural responses to simulated moving environments are not invariant for the direction of gaze. AB - Postural responses were measured for observers instructed to maintain an erect position when viewing a visual scene, which stimulated motion of the observer relative to a corridor with texture on the walls. Both the direction and amplitude of the postural responses appeared to depend on the fixation direction of the observer. This result indicates that postural responses are not invariant with respect to fixation direction. Our results suggest that not one of the frequently suggested features in the optical flow in particular is used to maintain posture but rather that a combination of several optical flow components, that have been suggested in the literature, is relevant. PMID- 2311694 TI - Disynaptic tectal and pyramidal excitation of hindlimb motoneurons mediated by pontine reticulospinal neurons in the cat. AB - 1. The pathway mediating disynaptic tectal and pyramidal excitation of hindlimb motoneurons was analyzed in cats anesthetized with alpha-chloralose or pentobarbital. Stimulation of the contralateral tectofugal fibers induced EPSPs in flexor and extensor hindlimb motoneurons (118/171). EPSP latencies, measured from the monosynaptically evoked descending volley, were 0.8 ms or less in 34 of the 118 motoneurons, suggesting disynaptic linkage from the tectum. The latencies tended to be shorter in motoneurons innervating proximal muscles than in those innervating distal muscles. 2. Stimulation of the cerebral peduncle induced EPSPs only in a small proportion of motoneurons (7/32). But the peduncular stimulation exhibited a marked facilitatory effect on the tectal EPSPs in most of the tested motoneurons (23/27), showing convergence of tectal and peduncular inputs onto relay cells. 3. In animals whose pyramid was transected, the tectal EPSPs were still facilitated by peduncular stimulation in 45 of 48 tested motoneurons. The time course of facilitation indicated convergence of tectofugal and corticofugal fibers onto brainstem relay neurons. 4. Projection of single neurons in the nucleus reticularis pontis caudalis (NRPC) to the gray matter of the hindlimb segments was examined by mapping thresholds of antidromic activation. Twelve of 13 tested neurons were excited by contralateral tectal stimulation at short latencies, probably monosynaptically. Four of them were found to project to lamina IX. Two of the 3 tested neurons projecting to lamina IX were found to receive excitatory input from the cerebral peduncle. 5. Stimulation of NRPC induced monosynaptic EPSPs in hindlimb motoneurons. In 19 motoneurons, the NRPC induced monosynaptic EPSPs were facilitated by a conditioning tectal shock. This indicated that the tectal stimulus lowered thresholds of direct activation of cell bodies of premotor NRPC neurons. The time course of the facilitation indicated that the NRPC neurons received monosynaptic tectal excitation. The results provide strong evidence that NRPC neurons are involved in mediating disynaptic tectal excitation of hindlimb motoneurons. PMID- 2311695 TI - Picture recognition vs. picture discrimination learning in monkeys with medial temporal removals. AB - Three monkeys with complete ablations of temporal-lobe limbic structures and three unoperated controls were compared in an automated testing apparatus for their ability to remember pictures presented between 1 and 180 seconds previously, as well as to learn picture discriminations in which successive trials with a given pair were separated by either 20 seconds or 24 hours. The operated animals were not impaired in picture discrimination learning under either condition and they were not impaired in picture recognition memory up to about 10 seconds. At 10 seconds and beyond, however, the operated animals showed rapid deterioration of picture memory. The results demonstrate that the limbic system's selective contribution to learning and retention uncovered initially with objects applies equally to pictures, this contribution being essential for recognition memory but not for discrimination habits. The results demonstrate further that, as in humans, temporal-lobe limbic structures are essential for recognition only when the retention test exceeds the immediate memory span of a few seconds. PMID- 2311696 TI - Effects of ketamine on GABA-evoked excitability of peripheral nerve. AB - The effects of the dissociative anaesthetic, ketamine on GABA-evoked changes in the excitability of myelinated fibers of dorsal and ventral roots of isolated bullfrog sciatic nerves were examined. Ketamine alone (0.01-1000 microM) evoked small increases (less than 5%) in dorsal root fiber excitability, as reflected in the half-maximal A-fiber compound action potential when concentrations were greater than 10 microM; with greater than or equal to 0.1 microM even larger increases (greater than or equal to 10%) were elicited in the ventral root fibers. As well, the increases evoked by greater than or equal to 10 microM ketamine were followed by graded decreases. 0.1 and 10 microM ketamine, concentrations which by themselves had small or no effect, produced a dose dependent depression of the large increases in excitability which are induced by activation of GABA receptors. In the presence of ketamine GABA concentration response curves of the dorsal root fibers showed depression of the maximal response, while those of the ventral root fibers were shifted to the right. This apparent antagonism of GABA responses by ketamine may arise from blockade of receptor-mediated effects (e.g. K+/Cl- currents and/or secondary depolarization from K+ accumulation), but could also be caused by a selective potentiation of hyperpolarizing receptors. PMID- 2311697 TI - Neural control of vocalization in bats: mapping of brainstem areas with electrical microstimulation eliciting species-specific echolocation calls in the rufous horseshoe bat. AB - 1. The functional role of brainstem structures in the emission of echolocation calls was investigated in the rufous horseshoe bat. Rhinolophus rouxi, with electrical low-current microstimulation procedures. 2. Vocalizations without temporal and/or spectral distortions could be consistently elicited at low threshold currents (typically below 10 microA) within three clearly circumscribed brainstem areas, namely, the deep layers and ventral parts of the intermediate layers of the superior colliculus (SC), the deep mesencephalic nucleus (NMP) in the dorsal and lateral midbrain reticular formation and in a distinct area medial to the rostral parts of the dorsal nucleus of the lateral lemniscus. The mean latencies in the three vocal areas between the start of the electrical stimulus and the elicited vocalizations were 47 msec, 38 msec and 31 msec, respectively. 3. In pontine regions and the cuneiform nucleus adjacent to these three vocal areas, thresholds for eliciting vocalizations were also low, but the vocalizations showed temporal and/or spectral distortions and were often accompanied or followed by arousal of the animal. 4. Stimulus intensity systematically influenced vocalization parameters at only a few brain sites. In the caudo-ventral portions of the deep superior colliculus the sound pressure level of the vocalizations systematically increased with stimulus intensity. Bursts of multiple vocalizations were induced at locations ventral to the rostral parts of the cuneiform nucleus. No stimulus-intensity dependent frequency changes of the emitted vocalizations were observed. 5. The respiratory cycle was synchronized to the electrical stimuli in all regions where vocalizations could be elicited as well as in more ventrally and medially adjacent areas not yielding vocalizations on stimulation. 6. The possible functional involvement of the "vocal" structures in the audio-vocal feedback system of the Dopplercompensating horseshoe bat is discussed. PMID- 2311698 TI - Processing of amplitude modulated sounds in the medial geniculate body of squirrel monkeys. AB - The responses of single and multi units in the medial geniculate body of the squirrel monkey (Saimiri sciureus) to modulation frequency, modulation depth and changes in absolute intensity of sinusoidally amplitude modulated (AM) sounds were studied. Both spike-frequency and spike rate modulation were used as a measure for neuronal response. Spike rate modulation was derived from FFT (Fast Fourier-Transformation) analysis of the PSTHs. In all cases (N = 133) spike rate modulation was shown to be dependent on the stimulus modulation frequency: Most neurons responded best to one modulation frequency, i.e., they showed a modulation transfer function with bandpass characteristic; only a few displayed a low pass or multiple peaked transfer characteristic. The majority of the neurons responded best in a range from 4 to 64 Hz, with a peak at 32 Hz and a median at 16 Hz. Such modulation frequencies are common in parts of the species vocal repertoire. PMID- 2311699 TI - Peripheral nerve section induces increased levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity in axotomized motoneurons. AB - By use of fluorescence immunohistochemistry it is shown that sciatic nerve section in cat and rat induces increased levels of immunoreactive calcitonin gene related peptide (CGRP) in axotomized motoneurons. In the rat, this effect was clearly seen at 2-5 days postoperatively, but could not be demonstrated after 11 21 days. These findings are discussed in relation to previously proposed roles for CGRP in motoneurons. PMID- 2311700 TI - Central auditory conduction time in the rat. AB - Central conduction time is the time for an afferent volley to traverse the central pathways of a sensory system. In the present study, central auditory conduction time (CACT) was calculated for the rat, the first such formal measurement in any animal. Brainstem auditory evoked potentials (BAEPs) were recorded simultaneously with the primary response of the auditory cortex (P1). The latency of wave II of the BAEP, which arises in the cochlear nucleus, was subtracted from that of P1. This yielded a mean CACT of 6.6 ms. The results confirm a previous theoretical estimate that CACT in the rat is at least twice as long as central somatosensory conduction time. PMID- 2311701 TI - Amplitude modulation of the quadriceps H-reflex in the human during the early stance phase of gait. AB - Amplitude modulation of the quadriceps H reflex was investigated during the early part of the stance phase of gait in normal human subjects. Stability of the M wave was used to ensure constancy of the effective stimulus strength. In all subjects there was a progressive decrease in the reflex amplitude throughout the early knee flexion (yield of the knee), whereas the quadriceps EMG activity remained constant or even increased. At an equal stimulus strength and EMG level, the reflex was often larger at the onset of the stance phase of gait than during voluntary contraction, whereas it was always smaller during the knee extension following the yield of the knee. It is argued that changes in presynaptic inhibition of quadriceps Ia terminals could account for this amplitude modulation of the monosynaptic reflex during gait. The possible role of changes in the gain of the quadriceps stretch reflex during bipedal gait is discussed. PMID- 2311702 TI - Spatial properties of vertical eye movement-related neurons in the region of the interstitial nucleus of Cajal in awake cats. AB - 1. Maximal activation directions of vertical burst-tonic and tonic neurons in the region of the interstitial nucleus of Cajal (INC) were examined in alert cats during vertical vestibulo-ocular reflex induced by sinusoidal rotation (at 0.11 Hz +/- 10 deg, or 0.31 Hz +/- 5 deg) in a variety of vertical planes using a null point analysis. The results were compared with the angles of anatomical and functional planes of vertical canals reported by Blanks et al. (1972) and Robinson (1982), and with the angles of vertical eye muscles measured in this study and by Ezure and Graf (1984). 2. Maximal activation directions of 23 cells (21 burst-tonic and 2 tonic neurons) were determined from their responses during rotation in 4 or more different vertical planes. All cells showed sinusoidal gain curves and virtually constant phase values except near the null regions, suggesting that their responses were evoked primarily by canal inputs. Phase values of 5 cells near the null regions depended on the rotation plane, suggesting additional otolith inputs. We used a measurement error range of +/- 10 deg for calculating the maximal activation directions from the null regions of individual cells and the values of error ranges of null calculation. Of the 23, the maximal activation directions of 7 cells were outside the measurement error ranges of vertical eye muscle angles and within the ranges of vertical canal angles (class A), those of 5 cells were within the ranges of eye muscle angles and outside the ranges of vertical canal angles (class B), and those of the remaining 11 cells were in the overlapping ranges for both angles (class C). Even if only the cells in which 5 or more measurement points were taken to determine maximal activation directions (n = 15), the results were similar. During vertical rotation with the head orientation +60 deg off the pitch plane, dissociation of cell activity and vertical compensatory eye movement was observed in 5 cells in class A or C that had null angles near +45 deg. These results suggest that the cells in class A and B carried individual vertical canal and oculomotor signals, respectively, although it is difficult to tell for the majority of cells (class C) which signals they reflected. Some cells in class A and C were antidromically activated from the medial longitudinal fasciculus at the level of abducens nucleus, suggesting that the signals carried by these cells may be sent to the lower brainstem.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2311703 TI - Neuronal activity related to vertical eye movement in the region of the interstitial nucleus of Cajal in alert cats. AB - (1) Discharge characteristics of neurons in the region of the interstitial nucleus of Cajal (INC) were studied in alert cats during spontaneous or visually induced eye movement and sinusoidal vertical (pitch) rotation. Activity of a majority of cells (n = 68) was closely related to vertical eye position with or without bursting activity during on-direction saccades. They were called vertical burst-tonic (n = 62) and tonic (n = 6) neurons. Mean discharge rates for individual cells when the eye was near the primary position ranged from 35 to 133 (mean 75) spikes/s with a coefficient of variation (CV) ranging from 0.04 to 0.29 (mean 0.15). Average rate position curves were linear for the great majority of these cells with a mean slope of 3.9 +/- 1.2 SD spikes/s/deg. (2) The burst index was defined as the difference in discharge rate between maximal rate during an on direction saccade and the tonic rate after the saccade. The values of mean burst index for individual cells ranged from 8 to 352 (mean 135) spikes/s. Tonic neurons had a burst index lower than 60 spikes/s and were distributed in the lower end of the continuous histogram, suggesting that burst-tonic and tonic neurons may be a continuous group with varying degrees of burst components. During off-direction saccades, a pause was not always observed, although discharge rate consistently decreased and pauses were seen when saccades were made further in the off-direction toward recruitment thresholds. Significant positive correlation was observed between average discharge rate during off- as well as on-direction saccades and tonic discharge rate after saccades for individual cells, which was not due to cats making saccades mainly from the primary position. (3) During pitch rotation at 0.11 Hz (+/- 10 deg), burst-tonic and tonic neurons had mean phase lag and gain of 128 (+/- 13 SD) deg and 4.2 (+/- 1.7 SD) spikes/s/deg/s2 relative to head acceleration. During pitch rotation of a wide frequency range (0.044-0.495 Hz), the values of phase lag were mostly constant (120-140 deg), while simultaneously recorded vertical VOR showed the mean phase lag of 178 deg. Vertical eye position sensitivity and pitch gain (re head position) showed significant positive correlation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2311704 TI - Elimination of intramedullary axon collaterals of cat spinal alpha-motoneurons following peripheral nerve injury. AB - The motor nerve supplying the medial gastrocnemius (MG) muscle was transected in the popliteal fossa of adult cats. The proximal nerve stump was ligated to prevent reinnervation. Three, six or twelve weeks later, axotomized MG motoneurons were intracellularly labelled with horseradish peroxidase, and the morphology of their intramedullary axon collateral systems was investigated quantitatively. The results were compared with corresponding data obtained from normal MG motoneurons. The peripheral chronic axotomy induced a gradual decrease in the number of recurrent axon collaterals originating from the lesioned MG motoraxons within the spinal cord. At 12 weeks postoperatively, this decrease amounted to 40%. The elimination preferentially involved axon collaterals originating from juxta-somatic regions of the motoraxons. In the axon collateral trees persisting in the axotomized MG neurons the tree size, branching patterns and number of synaptic boutons were all normal. Thus, no signs of a gradual deterioration of individual axon collateral systems were observed at any postoperative stage studied. The results are discussed in relation to other retrograde degenerative and regenerative events induced by axotomy. PMID- 2311705 TI - Plasticity of recurrent inhibitory reflexes in cat spinal motoneurons following peripheral nerve injury. AB - Chronic axotomy of a peripheral motor nerve in cat causes a gradual reduction in the number of intramedullary axon collaterals originating from the axotomized motoneurons (Havton and Kellerth 1984, 1989). This axon collateral elimination would be expected to reduce the amount of recurrent inhibitory reflex actions mediated by these cells. The aim of the present study was to investigate the recurrent inhibition originating from axotomized motoneurons and, also, to see whether the elimination of axon collaterals from the axotomized neurons might induce secondary compensatory changes in the recurrent inhibitory pathways originating from synergistic non-lesioned motoneurons. The results, which were obtained by means of intracellular recordings and monosynaptic reflex testing, indicate that postoperative enhancement of reflex actions may take place in the recurrent inhibitory pathways persisting in the axotomized motoneurons as well as in those originating from synergistic nonlesioned motoneurons. It is suggested that the site of compensatory enhancement is at the synaptic reflex contacts between the motoraxon collaterals and the inhibitory Renshaw interneurons. PMID- 2311706 TI - Frequency and space representation in the inferior colliculus of the FM bat, Eptesicus fuscus. AB - The tonotopic organization and spatial sensitivity of 217 inferior collicular (IC) neurons of Eptesicus fuscus were studied under free field stimulation conditions. Acoustic stimuli were delivered from a loudspeaker placed 21 cm ahead of the bat to determine the best frequency (BF) and minimum threshold (MT) of isolated IC neurons. A BF stimulus was then delivered as the loudspeaker was moved horizontally across the frontal auditory space of the bat to locate the best azimuthal angle (BAZ) at which the neuron had its lowest MT. The stimulus was then raised 3 dB above the lowest MT to determine the horizontal extent of the auditory space within which a sound could elicit responses from the neurons. This was done by moving the loudspeaker laterally at every 5 degrees or 10 degrees until the neuron failed to respond. These measurements also allowed us to redetermine the BAZ at which the neuron fired maximal number of impulses. Electrodes were placed evenly across the whole IC surface and IC neurons were sampled as many as possible within each electrode penetration. Tonotopic organization and spatial sensitivity were examined among all 217 IC neurons as a whole as well as among IC neurons sequentially sampled within individual electrode penetrations. The whole population of 217 IC neurons is organized tonotopically along the dorsoventral axis of the IC. Thus, low frequency neurons are mostly located dorsally and high frequency neurons ventrally with median frequency neurons intervening in between. The BAZ of these 217 IC neurons tend to shift from lateral to medial portions of the contralateral frontal auditory space with increasing BF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311707 TI - Firing relations of lateral septal neurons to the hippocampal theta rhythm in urethane anesthetized rats. AB - The firing of lateral septal neurons was examined in relation to the hippocampal theta rhythm in urethane anesthetized rats. In general, the firing rates of these cells were low during both theta and non-theta EEG states. There was no significant change in firing rate between the two states (theta: 8.5 +/- 9.9 spks/sec; non-theta: 6.0 +/- 5.3). Sixty-four of 68 cells fired simple spikes and 4 cells were found to fire bursts of action potentials (complex-spikes). Approximately 30% (21/65) of the cells showed a significant phase relation to the hippocampal theta rhythm. The preferred phases of firing of these 21 cells were broadly distributed. The possibility that the phase-locked firing of LSN cells is due to the phase-locked firing of hippocampal projection cells is discussed. PMID- 2311708 TI - Gating of tactile input from the hand. I. Effects of finger movement. AB - Intraneural microstimulation within the median nerve of alert healthy subjects was used to evoke tactile sensations at threshold for conscious detection. The effect of movement on these sensations was studied by asking the subjects to estimate their magnitude before, during and after movement of the appropriate finger at different speeds. It was found that sensations of flutter and pressure were both attenuated by movement, as was the magnitude of spontaneous paraesthesiae. The degree of sensory inhibition correlated positively with speed of movement and was comparable to the previously reported reduction in cortical somatosensory evoked potentials by movement, using suprathreshold stimuli. These results indicate that (i) movement inhibits tactile sensations of different qualities, (ii) such inhibition is velocity-dependent, and (iii) threshold sensations are amenable to central modulation short of their abolition. It is likely that the mechanisms of inhibition of exteroceptive inputs during movement are contingent upon the character of the sensory stimulus and the nature of the motor task. PMID- 2311709 TI - Metabolic labeling of Entamoeba histolytica antigens: characterization of a 28 kDa major intracellular antigen. AB - The in vivo incorporation of radiolabeled amino acids into antigens of Entamoeba histolytica, HM-1:IMSS, is reported. Immunoprecipitation with sera from patients with invasive amebiasis revealed a 28-kDa antigen present in whole cell lysates of E. histolytica. This antigen was of cytoplasmic origin, as indicated by cell fractionation and Triton X-114 detergent-phase separation. Immunoprecipitation, using sera from patients with invasive amebiasis and symptomless cyst passers, revealed the 28-kDa antigen as the major antigen recognized by the sera tested. Immunoprecipitation analysis using radiolabeled-released proteins instead of whole cell lysates showed a number of bands, including the 28-kDa antigen. The data suggest that the 28-kDa antigen is of cytoplasmic origin or is released from the cytoplasmic compartment. PMID- 2311710 TI - Trypanosoma brucei: two-dimensional gel analysis of the major glycosomal proteins during the life cycle. AB - Kinetoplastid organisms possess a unique organelle, the glycosome, which compartmentalizes the Embden-Meyerhof segment of glycolysis and several other metabolic pathways. In Trypanosoma brucei many of the enzyme activities localized to the glycosome are stage regulated. Two-dimensional gel analysis was used to examine the characteristics, expression, and biosynthesis of the major glycosomal proteins. Two-dimensional gel maps of glycosomes from slender bloodforms and late intermediate-stumpy bloodforms (the precursors of procyclic forms) were indistinguishable, while those of procyclic form glycosomes showed extensive differences. Glycosomal phosphoenolpyruvate carboxykinase and malate dehydrogenase were identified to have subunit molecular weights of 60 and 34 kDa, respectively. We detected two hitherto undescribed glycosomal proteins, one of which is found only in bloodforms. All of the major proteins, except glucose phosphate isomerase, were highly basic. Stage regulation of glycosomal enzyme activities correlated with stage regulation of specific protein biosynthesis. PMID- 2311711 TI - Schistosoma mansoni: influence of Biomphalaria glabrata size on susceptibility to infection and resultant cercarial production. AB - Biomphalaria glabrata snails of the same age, but different sizes, were used to determine size-related susceptibility to Schistosoma mansoni miracidial infection and the influence of snail size on total cercarial production. Snails with shell diameters from less than 5 to greater than 17 mm were individually exposed to one or several miracidia, depending on the experiment. In snails exposed to multiple numbers of miracidia, the percentage of snails which developed patent infections was lower in snails with larger shell sizes. This was also reflected by fewer primary sporocysts per infected snail found in tissues of the larger snails. Upon determining cercarial production in these groups over a 1-month period there were no statistical differences between any groups in the numbers of cercariae produced per snail. However, upon determining the number of successful primary sporocysts found in cohort snails of each size group, cercarial production increased as a function of the number of successful primary sporocysts. This was verified by examining cercarial production in various size snails with known monomiracidial infections. Our data therefore confirm and extend earlier work using snails infected with unknown numbers of miracidia and clearly show that total S. mansoni cercarial development and decreased susceptibility of snails is a direct reflection of snail size and not necessarily age of the snail. PMID- 2311712 TI - Anisakis simplex: histopathological changes in experimentally infected CBA/J mice. AB - Third-stage juveniles (L3) of Anisakis simplex, surgically implanted into the abdominal cavity of CBA/J mice and necropsied at 7, 14, or 21 days postinfection (PI), embedded in the gut mesentery and only rarely invaded viscera. Histologically, intense aggregations of neutrophils adjacent to the parasites were noted at Day 7 PI. At Day 14 PI, mature granulomata consisting mostly of eosinophils and large numbers of fibroblasts and associated collagen were observed. Granulocytes and occasionally multinucleate giant cells occupied the host-parasite interface. At 21 day PI, lesions displayed the predominance of connective tissue. Multinucleate giant cells were found adjacent to the L3 with eosinophils adjacent to parasite remnants or scattered within the walls of the granulomata. Most L3 were viable at Days 7 and 14 PI; however, at Day 21 PI the L3 were dead and invaded by inflammatory cells. Hematological findings indicated that infected mice had a neutrophilia of varying magnitude regardless of the number of worms implanted. Eosinophil levels as a percentage of the total leukocyte pool in peripheral blood always remained at or below normal limits. On Days 7 and 14 PI, the peripheral blood showed an increase in neutrophils that began to return to normal values at 21 day PI. Conversely, peripheral blood eosinophils decreased on Days 7 and 14 PI and returned to normal values on Day 21 PI. Surgical implantation of A. simplex L3 into mice produced both a hematological and histological picture consistent with that seen in human anisakiasis. PMID- 2311713 TI - Dirofilaria immitis: molting process of third-stage larvae. AB - The objective of this study was to determine the molting process of Dirofilaria immitis third-stage larvae (L-3) to fourth-stage larvae (L-4), as it occurred in vitro. After 48 hr in vitro, the L-4 epicuticle was completely formed, and by 72 hr there was a clear separation between the L-3 and L-4 cuticles. The thickness of the newly formed L-4 cuticle was significantly less than that which has been described for larvae recovered from dogs after a similar incubation time period. If culture conditions were lacking in bovine albumin or proper temperature, larvae successfully developed the L-4 epicuticle but did not complete ecdysis. The molting process of D. immitis L-3 was thus shown to be multistepped with different factors required to induce the various developmental phases. PMID- 2311714 TI - Plasmodium yoelii: comparative antimalarial activities of dietary fish oils and fish oil concentrates in vitamin E-deficient mice. AB - Feeding vitamin E-deficient diets containing either fish oils such as menhaden, salmon, or anchovy oil or fish oil concentrates based on n-3 ethyl esters or free fatty acids protected mice against Plasmodium yoelii as indicated by decreased parasitemia and improved survival. The fish oil concentrates depressed plasma tocopherol levels more strongly in vitamin E-supplemented mice than the menhaden oil. The free fatty acid concentrate appeared to suppress parasitemia in vitamin E-deficient mice better than the menhaden oil, although ultimate survival was similar in both groups. Dietary manipulation of host antioxidant status offers promise as a possible means of malaria control. PMID- 2311715 TI - Trichinella spiralis: murine strain variation in response to monoclonally defined, protective, nonstage-specific antigens. AB - Nine hybridoma cell lines secreting monoclonal antibodies (mAbs) against Trichinella spiralis muscle larvae (ML) excretory/secretory antigens (ESA) were developed. Two mAbs, 6-D8-E3 (6D8) and 6-B1-G10 (6B1), were studied in detail. Western blot analysis using ML ESA showed that 6D8 recognized 35- and 40-kDa constituents whereas 6B1 identified a doublet of 33 kDa. However, Western blots of SDS-PAGE of crude ML homogenate showed that 6D8 identified proteins of approximately 35 and 43-60 kDa, whereas 6B1 recognized bands of 42-50 kDa. These results indicated substantial apparent MW differences between secreted and nonsecreted proteins recognized by both mAbs. Neither 6D8 nor 6B1 reacted with adult worm ESA, but both recognized antigens in aqueous extracts of homogenates of whole adult worms. Competitive inhibition experiments using ML ESA as a target demonstrated that the antigen epitopes recognized by monoclonals 6D8, 6B1, a rat mAb, 9D4, and a 37-kDa antigen previously defined were noncross-reactive. MAbs 6D8, 6B1, and 9D4 were used to isolate proteins possessing target determinants by affinity chromatography from crude ML homogenates. Each mAb isolated distinct protein species as determined by SDS-PAGE (6B1, approximately 42 kDa; 6D8, approximately 28, 37, and 61 kDa; 9D4, approximately 29, 33, 38-57, 80, and 86 kDa). NFS mice responded in a dose-dependent manner to affinity-purified antigens and were 25-fold more effective (by weight of antigen) than either C3Heb/Fe(C3H) or B10.BR mice. Immunization of mice with 6D8, 6B1, or 9D4 antigens induced strong protection against a subsequent challenge infection in NFS mice as indicated by accelerated intestinal adult worm expulsion, reduced fecundity of the female worms, and reduction of ML burden. Affinity-isolated antigens stimulated in vitro proliferation of spleen and MLN cells from immune mice; however, the mitogenic response to these antigens barely varied among NFS, C3H, and B10.BR strains. PMID- 2311716 TI - Effects of larval tapeworm (Taenia taeniaeformis) infection on reproductive functions in male and female host rats. AB - This report examined the effects of larval tapeworm infection on the reproductive functions in both male and female host rats. Female rats were matched by age, then randomly assigned to control and treatment groups (infected with larval tapeworms). Estrous cycles were determined by vaginal smear with 95% of the control group exhibiting 4-day normal cyclicity and only 55% of the treated group exhibiting normal cycles. Female fertility was then evaluated for the normally cycling rats based on the percentage of successful matings on the evening of proestrus, number of implantation sites on Day 8 of pregnancy, and number of pups born at term. The normally cycling rats exhibited 96% successful mating, 12.95 +/ 1.80 implantation sites, and 11.20 +/- 1.80 pups born. Five months after larval tapeworm infection, the fertility parameters were decreased to 79%, 9.10 +/- 1.20, and 7.50 +/- 1.50, respectively. The control females were then used in a study of male fertility after larval tapeworm infection employing the same parameters used to test female fertility. At the onset of the study, control groups exhibited 95% successful mating, 12.50 +/- 1.50 implantation sites, and 11.60 +/- 1.60 pups born at full term. After the 5-month infection period, the parameters were substantially reduced to 29%, 6.20 +/- 0.80 implantation sites, and 5.10 +/- 0.80 pups, respectively. Average testosterone concentrations in serum and testis from control male rats were 8.80 +/- 0.95 ng/ml and 3.88 +/- 0.25 ng/mg protein, respectively. After the 5-month infection period, these levels were reduced to 2.47 +/- 0.31 ng/ml and 1.28 +/- 0.12 ng/mg protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311717 TI - The fractal lung: universal and species-related scaling patterns. AB - The mammalian lung exhibits features of a fractal tree: heterogeneity, self similarity and the absence of a characteristic scale. The finite nature of the lung ultimately limits the range over which self-similarity scaling characteristics are applicable. However, generalization based on the scaling features of fractals, provides unique insight into geometric organization of anatomic structures. Furthermore, the mathematical theory of renormalization groups provides a description of the harmonically-modulated inverse power-law scaling observed for bronchial tree dimensions observed in different species. Compared to several mammalian species (dog, rat, hamster), the human lung shows marked differences in the phase of the harmonic modulation for both length and diameter measurements. These inter-species scaling differences suggest that evolutionary factors modify certain universal features of morphogenesis. PMID- 2311718 TI - Inhibitory effects of spermine and spermidine on muscle calpain II. AB - The muscle enzyme calpain II, in contrast to muscle calpain I, was markedly inhibited by millimolar concentrations of the polyamines spermine and spermidine. These compounds and the calpain inhibitor calpastatin had synergistic inhibitory effects on calpain II. These results suggest that the polyamines may have possible regulatory effects on the in vivo activity of calpain II enzymes. PMID- 2311719 TI - Hypothalamic histamine modulates adaptive behavior of rats at high environmental temperature. AB - Histamine content in the rat hypothalamus was lower at 4 degrees C and higher at 31 degrees C compared to that at 21 degrees C. Pretreatment with alpha fluoromethylhistidine, a 'suicide' inhibitor of histamine decarboxylase, attenuated both the increased level of hypothalamic histamine and rat adaptive behavior at 31 degrees C. Increase of histamine content in the hypothalamus appears to be an important factor contributing to rat adaptive behavior to high environmental temperature. PMID- 2311720 TI - Stress-induced increase in noradrenaline release in the rat hypothalamus assessed by intracranial microdialysis. AB - The hypothalamic microdialysis of conscious rats was used to investigate the effects of immobilization stress (20 min) on extracellular noradrenaline (NA) levels. The stress significantly increased NA levels relative to basal efflux by 106% and this elevation continued for 40 min after release from stress. PMID- 2311721 TI - Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats. AB - The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS. PMID- 2311722 TI - Microtubule inhibitors block the morphological changes induced in Drosophila blood cells by a parasitoid wasp factor. AB - The shape change of Drosophila melanogaster blood cells (lamellocytes) from discoidal to bipolar that is caused by a factor from the female parasitoid Leptopilina heterotoma is blocked by the tubulin inhibitors vinblastine and vincristine in vitro. The actin inhibitor, cytochalasin B, causes arborization of Drosophila lamellocytes and acts synergistically with the wasp factor to alter lamellocyte morphology. Lamellocyte aborization induced by cytochalasin B is blocked by simultaneous treatment with vinblastine. These observations indicate that the changes in lamellocyte shape induced by both the wasp factor and cytochalasin B require microtubule assembly. PMID- 2311723 TI - Acute lung reaction due to zinc inhalation. AB - A 27-yr-old man began work at a company that produces concrete pipes in April 1987. The pipes are linked with rings covered with zinc. In September 1987, he was transferred to a new job in the same plant where he had to heat zinc wires and shoot the heated zinc in powder form onto the iron rings. He had no past personal nor family atopic history. Two weeks after he began in his new job, he experienced an episode of chills with muscle aches and dyspnoea at the end of a working day. The fever persisted until the next day, at which time he saw a physician. A chest radiograph revealed diffuse interstitial shadows. He was off work for 10 days. His symptomatology disappeared and his chest radiograph cleared. He went back to work and experienced a similar episode. He remained away from work for one month, after which specific inhalation challenges were performed. On a control day, there were no significant changes in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), or buccal temperature. Two white blood counts (WBC) showed 8,400 and 8,500 white cells. He was exposed to his usual work environment for one hour on two consecutive days. On both occasions, there were significant falls in FEV1 (16% and 20%) and FVC (10% and 11%), occurring 4-6 h after exposure. Buccal temperature reached 38.1 and 38.7 degrees C on the two occasions, and WBC were 17,000 and 15,900 at the end of each day. Precipitins were negative and specific IgG antibodies could not be detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311724 TI - Multiple pulmonary nodules. PMID- 2311725 TI - No effect of oral high frequency oscillation combined with forced expiration manoeuvres on tracheobronchial clearance in chronic bronchitis. AB - This study compared the effect of oral high frequency oscillation (OHFO) with the effect of the forced expiration technique (FET) on tracheobronchial clearance. Eight patients with chronic bronchitis were investigated (mean age 60 +/- 10 yrs, mean forced expiratory volume in one second (FEV1) 68 +/- 27% predicted, mean sputum production 33 +/- 9 g.day-1). OHFO was applied at the respiratory system resonant frequency of each patient (range 9.2-25 Hz) and combined with huffing. FET included breathing exercises, huffing and postural drainage. Duration of both OHFO and FET was 30 minutes. Tracheobronchial clearance was measured by means of a radio-aerosol technique. At 60 mins after start of the treatment mean tracheobronchial retention was 70 +/- 26% after OHFO, 54 +/- 26% after FET and 76 +/- 18% in the control run, which included huffing only. OHFO was not significantly different from control. FET was significantly different (p less than 0.02) from both OHFO and control. It is concluded that OHFO has no effect on tracheobronchial clearance in chronic bronchitis. PMID- 2311726 TI - The bronchodilator response from increasing doses of terbutaline inhaled from a multi-dose powder inhaler (Turbuhaler). AB - Twelve adult asthmatics inhaled single doses of 0.5, 2.0 or 4.0 mg of terbutaline, respectively, via Turbuhaler, on three separate days. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and pulse rate were measured 15, 30, 45 and 60 min after inhalation from the inhaler and then hourly up to 8 h. The results showed that a more rapid onset of action, a greater maximal response and a longer duration of action can be achieved by exceeding the standard dose of terbutaline of 0.5 mg. The incidence of adverse effects was very low even at the highest dose, 4 mg. This study emphasizes the need for individual dosing of inhaled bronchodilators. PMID- 2311727 TI - Comparison between theophylline and an adenosine non-blocking xanthine in acute asthma. AB - Enprofylline, a drug without adenosine antagonism and theophylline, a potent adenosine antagonist, were compared, double-blind, randomized, in acute asthma (n = 33). The drugs were given intravenously as loading over 10 min followed by maintenance infusion for 24 h. Mean final plasma levels were very high with enprofylline (14 mg.l), and larger than calculated with theophylline (16 mg.l). Seven patients had maximum levels of enprofylline ranging between 16 and 42 mg.l. Extreme plasma levels of enprofylline were not associated with any theophylline like central nervous system excitatory effects related to seizure-inducing ability. Some irregularities in the heart rhythm did not raise clinical problems and no significant difference between enprofylline and theophylline was recorded. At 1 h patients on enprofylline (mean plasma level: 5.7 mg.l) and theophylline (12.2 mg.l) had improved their peak expiratory flow rates by 31% and 15% (p less than 0.05), respectively. The improvement in lung function after 24 hours did not differ between treatments suggesting that the high levels of enprofylline were supramaximal for its anti-asthma effects in this situation. In conclusion, with enprofylline it is demonstrated that an adenosine non-blocking xanthine derivative may lack CNS-excitatory effects, but be more potent than theophylline in the treatment of acute asthma. PMID- 2311728 TI - Effects of pulmonary vasodilators on the remodelled pulmonary arterial tree in chronic alveolar hypoxia. PMID- 2311729 TI - Education of adult patients at an "asthma school": effects on quality of life, knowledge and need for nursing. AB - The effect of education of adult asthma patients at a special "asthma school" was studied with regard to knowledge of the disease and its treatment and quality of life measured by leisure activities, social interaction and psychological well being. We also studied if there were any differences in number of days in hospital and emergency visits before and one year after the asthma-school. Patients were randomised to an intervention group (7 men and 13 women) and a control group (7 men and 11 women). The age-range was 22-66 yrs. Both groups answered the same standardized and quantified questionnaires on three occasions, before the start of the asthma school, after five months and after twelve months. Both groups increased their knowledge of the disease and how to treat it, with slightly better results in the intervention group. The self-assessments all showed that patients in the intervention group felt better than those in the control group. The number of days in hospital as well as acute visits to out patients clinics were reduced significantly after the asthma school. The intervention did not influence spirometric variables. PMID- 2311730 TI - The effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid (15-HETE) on airway calibre and non-specific responsiveness in normal and asthmatic human subjects. AB - 15-hydroxyeicosatetraenoic acid (15-HETE) is the predominant oxidative metabolite of arachidonic acid in human lung. We have studied its effects on airway calibre and non-specific bronchial responsiveness (NSBR) in eight normal and eight asthmatic subjects. 15-HETE, at doses up to 70 nmol, had no effect on airway calibre in either group of subjects. However, 3 h after its administration, 15 HETE reduced NSBR in the normal subjects (geometric mean methacholine PD40 Vp30 increased by 2.29-fold from baseline compared with a corresponding 1.14-fold increase after diluent, p less than 0.05). Similarly, 4 h after inhaled 15-HETE, the spontaneous increase in NSBR in the asthmatics was completely inhibited (geometric mean histamine PD40 Vp30 decreased significantly to 0.41-fold of baseline after diluent (p less than 0.01) compared with a 1.1-fold increase after 15-HETE, p less than 0.01). These data suggest 15-HETE may play an autacoid role in airway function. PMID- 2311731 TI - The use of a vasodilator, felodipine, as an adjuvant to long-term oxygen treatment in COLD patients. AB - Eight patients with chronic obstructive lung disease (COLD) and pulmonary hypertension were given an infusion of a calcium antagonist, felodipine, during ongoing, long-term oxygen treatment (LTOT). The effects on central haemodynamics and ventilation-perfusion matching were studied. At rest pulmonary and systemic vascular resistances (PVR and SVR) were reduced by 18% (NS) and 26% (p less than 0.05), respectively. Cardiac output increased by 23%. There was a tendency to increased perfusion of low alveolar ventilation-perfusion ratio (VA/Q) areas (VA/Q less than 0.1) and to increased shunt compared to pretreatment values. Arterial oxygen tension (PaO2) fell by 0.7 kPa (p less than 0.001) but total oxygen transport increased by 23% (p less than 0.001). After treatment with oral felodipine (7.5-15 mg.day-1) for a mean time of 14 wks, PVR and SVR were reduced by 16% (p less than 0.05) and 7% (NS), respectively, as compared to pretreatment values at rest. Cardiac output rose by 13%. The VA/Q ratios and the PaO2 returned towards pretreatment values. The total oxygen transport increased by 11% (p less than 0.05) at rest and increased by 19% (p less than 0.05) during exercise as compared to the pretreatment value. The positive effect on central haemodynamics indicates that felodipine may be a valuable adjunct to ongoing LTOT. PMID- 2311732 TI - The action of platelet activating factor and its antagonism by WEB 2086 on human isolated airways. AB - This study investigated the direct and indirect effects of platelet activating factor (PAF, PAF-acether) on human isolated airways. PAF caused a single non repeatable contraction which was found to be variable both between lung samples and within tissues from the same lung. The range of contractions induced by PAF, 7 X 10(-8), M and 7 X 10(-7) M was 2-55% and 3-72% of the maximal response to carbachol, respectively. The PAF antagonist WEB 2086, 10(-6) M, inhibited the contraction induced by PAF, 7 X 10(-7) M, (p less than 0.05, n = 5). PAF caused a significant potentiation of the contractile effects of bolus doses of histamine. This potentiation was inhibited by WEB 2086, 10(-6) M, (p less than 0.05, n = 5). These results suggest firstly that the bronchoconstriction observed in man after PAF administration could be the result of an action of PAF on the smooth muscle or result from the action of a second mediator released by PAF from cells within the lung. Secondly, the bronchial hyperresponsiveness observed after PAF administration could be due to a specific alteration in smooth muscle sensitivity. The fact that WEB 2086 inhibited the contractile response to PAF and the potentiation of histamine-induced contraction would suggest that PAF receptors mediate these responses. PMID- 2311733 TI - Tracheal mucus clearance in high-frequency oscillation: effect of peak flow rate bias. AB - We have reported previously that high-frequency oscillation of the chest wall (HFO/CW) enhances the tracheal mucus clearance rate (TMCR) in dogs. This enhancement of TMCR may be due in part to the expiratory bias in peak flow rate (VE/VI greater than 1) that occurs during HFO/CW. We examined this factor in 8 anaesthetized, spontaneously breathing dogs by comparing TMCR during the following manoeuvers: 1) HFO/CW, applied by means of a thoracic cuff; 2) symmetric high-frequency oscillation via the airway opening (HFO/AO), applied by means of a piston pump driven by sinusoidal signal; 3) HFO/AO with an expiratory bias in peak flow, and 4) HFO/AO with an inspiratory bias in peak flow. All manoeuvers were of 5 min duration and were performed at 13 Hz and an oscillatory tidal volume of 1.5 ml.kg-1. In the latter two manoeuvers, the piston pump was driven by a nonsinusoidal signal such that peak VE/VI was greater than and less than unity, respectively. A high-impedance, cross-current flow of warmed, humidified air was provided at the tracheal tube. The order of manoeuvers 2, 3 and 4 was randomized, while manoeuver 1 was repeated at the end. TMCR was determined by direct bronchoscopic visualization of charcoal particle transport. Each HFO manoeuver was bracketed by a control period of spontaneous breathing. We found that TMCR during HFO/CW was 2.4 x control (p less than 0.001), in line with previous results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311734 TI - Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages. AB - Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis. PMID- 2311735 TI - Relationship between airway obstruction, desaturation during exercise and nocturnal hypoxaemia in cystic fibrosis patients. AB - We measured pulmonary function, responses to exercise and oxygen saturation (So2) at rest, and also before and during sleep in 24 patients with cystic fibrosis in a varying degree of severity. The pulmonary function indices analysed were forced expiratory volume in one second (FEV1), total lung capacity (TLC), measured by body plethysmography (TLC box) and Helium dilution (TLC He), residual volume measured by body plethysmography (RV) and the amount of trapped air (TA = TLC box TLC He). The exercise variables included symptom limited maximal oxygen uptake (Vo2max), maximum minute ventilation (VEmax) and So2, at rest in sitting position and during maximal exercise. So2 was measured by ear oximetry. The lowest mean So2 obtained in two consecutive nights over a period of 1 hour was taken as the indicator of nocturnal oxygen saturation. A high correlation existed between resting supine and sitting So2, and the degree of nocturnal hypoxaemia (0.84 and 0.76, respectively). Highly significant correlations existed also for the indices of airway obstruction, Vo2 max and lowest So2 at exercise versus the nocturnal lowest hourly mean So2. From all variables a resting So2 in the sitting position lower than 94% appeared to be most predictive of nocturnal desaturation and indicates a risk of nocturnal hypoxaemia in patients with cystic fibrosis. PMID- 2311736 TI - Lung growth of pre-adolescent children. AB - Lung growth was studied in 420 Dutch children aged 6-11 yrs. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) and maximal mid-expiratory flow (MMEF) were measured four times over a 2.5 yr period with a rolling-seal spirometer. In boys, pulmonary function increased with approximately the same velocity at all ages studied. In girls, however, the growth velocities of FVC and FEV1 increased markedly at age 10 yrs, and growth velocities of PEF and MMEF had increased already at age 9 yrs. The minimum pulmonary function growth velocity could not be determined from the available data in boys. In girls, the minimum pulmonary function growth velocities preceded the minimum height growth velocity at the onset of the pubertal growth spurt. All lung function growth rates were significantly associated with the growth rate of height. In girls, the growth rate of FVC was also associated with the weight growth rate. There was also some association between the growth rates of PEF and MMEF and age. In boys, there was a negative association between age and the growth rates of FVC and FEV1, after adjustment for the growth rate of height. PMID- 2311737 TI - Bronchial stump recurrence after surgery for bronchial carcinoma. AB - In 10 out of 295 patients (3.4%), followed-up after radical resection for non small cell bronchial carcinoma in the period from 1980 until 1986, bronchial stump recurrence developed. A good relationship was found between relapse time (4 52 months) and distance between the primary tumour and bronchial resection line (1-7 cm) (i.e. 5-8 months.cm-1) in 8 of the patients (p less than 0.01). The mean survival time after detection of the recurrence was 10 months (range 1-15 months), and was not clearly influenced by the therapy applied (resurgery, chemotherapy, radiation), nor by the TNM stage of the bronchial stump recurrence. PMID- 2311738 TI - Airways response of asthmatics after a 30 min exposure, at resting ventilation, to 0.25 ppm NO2 or 0.5 ppm SO2. AB - We compared the effect of inhaled NO2 and SO2 on airway tone and airway responsiveness in 14 nonsmoking mild asthmatics (mean +/- SD age 34 +/- 14 yrs; mean +/- SD baseline forced expiratory volume in one second (FEV1), 86 +/- 17% pred). On 3 separate days, 30 min tidal breathing (average minute ventilation 10.6 l.min-1) of either filtered air, 0.25 ppm NO2, or 0.5 ppm SO2 was followed by an isocapnic hyperventilation test with 0.75 ppm SO2. To determine the provocative ventilation necessary to increase specific airway resistance (sRaw) by 100% (PV100sRaw) ventilation was increased in steps of 15 l.min-1, each step lasting 3 min. Resting ventilation of filtered air, NO2, or SO2 was followed by a slight but significant overall decrease of sRaw from 8.8 to 7.7 cmH20.s-1, with no differences between the study days. Mean +/- SEM PV100sRaw(SO2) was 46.5 +/- 5.1, 37.7 +/- 3.5 and 45.4 +/- 4.2 l.min-1 after tidal breathing of filtered air, NO2, and SO2, respectively. PV100sRaw(SO2) was significantly lower after NO2 as compared to filtered air or SO2 (p less than 0.01). There was a significant correlation (rs = 0.86) between the individual shift of PV100sRaw(SO2) after NO2 and the shift after SO2 as compared to filtered air. From these individual comparisons we suggest that in asthmatics short-term exposure to NO2 at rest enhances airway responsiveness to hyperventilation of SO2 without altering airway tone, whereas short-term exposure with low concentrations of SO2 does not. PMID- 2311739 TI - Bronchoalveolar mastocytosis and lymphocytosis after nitrogen dioxide exposure in man: a time-kinetic study. AB - The combination of environmental chamber exposure and bronchoalveolar lavage (BAL) was used to study the time-course of the cell response in the human lung to nitrogen dioxide (NO2). Healthy subjects were exposed for 20 min to 7 mg NO2.m-3 (4 ppm), a concentration which occurs indoors in industries and is below the peak exposure limit for work places in most countries, 10 mg.m-3 (5.5 ppm). BAL was performed in all subjects several weeks before exposure and 4, 8, 24 and 72 h after exposure, in eight subjects at each time. Mastocytosis and lymphocytosis were found in BAL fluid 4-24 h after exposure, with normalization after 72 h. A mild increase in lysozyme positive macrophages was found 24-72 h after exposure. The time-course of the human pulmonary cell response to NO2, demonstrated in BAL fluid, represents a new and previously not reported finding after exposure to this common air pollutant. Our findings are diverging from results obtained in animal studies, using approximately the same NO2 concentrations, indicating that the results from the animal studies may not be transferable to man. PMID- 2311740 TI - A comparison of albumin and urea as reference markers in bronchoalveolar lavage fluid from patients with interstitial lung disease. AB - Lavage fluids were investigated for 67 subjects in 6 groups: 12 with active sarcoidosis, 8 with inactive sarcoidosis, 17 with pigeon breeder's disease, 10 asymptomatic pigeon breeders, 12 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects. Albumin and urea per ml of bronchoalveolar lavage fluid (BALF) were determined for each subject together with percentage return of fluid (BAL%). Novel assay systems were employed to measure urea and albumin and these were compared with existing analytical techniques. When compared with the control group, we found that urea per ml of BALF was not statistically different for all other groups, except those with pigeon breeder's disease who had significantly raised levels. For albumin, however, three groups had significantly higher levels than the controls, namely those with active sarcoidosis, pigeon breeder's disease and IPF. BAL% return showed no significant differences for any group when compared with the controls. We conclude that since albumin is significantly raised in most patients with interstitial lung disease it does not represent a suitable marker for the quantitation of reactive proteins in BALF. Urea shows much less variability between groups than does albumin, and hence in the absence of a proven alternative represents the most reliable estimate available of epithelial lining fluid dilution during the lavage procedure, providing dwell time is kept to a minimum. PMID- 2311741 TI - Phagocytic properties and organelle motility of pulmonary macrophages from smokers and nonsmokers estimated in vitro by magnetometric means. AB - Monolayer cultures of pulmonary macrophages (PM) from 11 smokers (S) and 9 nonsmokers (NS) were incubated with submicrometric ferromagnetic Fe3O4 particles for one hour. After magnetization by an externally applied pulse magnetic field, the aligned Fe3O4 particles, located in the phagosomes and secondary lysosomes of the PM, emanated a remanent magnetic field which decayed with time. The initial field strength, B0, which is proportional to the amount of phagocytosed Fe3O4 particles, was 13.24 nT (SE 0.79 nT) in S and 11.74 nT (SE 1.39 nT) in NS. Ten nT correspond to roughly 4 micrograms Fe3O4. The initial rate of decay of the remanent field (during the first 60 s after magnetization), lambda 0, is proportional to the rate of particle misalignment. Therefore, lambda 0, is hypothesized to be an estimate of organelle motility. It was found to be the same in S and in NS, being 3.14 x 10(-3).s-1 (SE 0.18 x 10(-3).s-1) in S and 3.17 x 10(-3).s-1) (SE 0.22 x 10(-3).s-1) in NS. These results suggest that, in vitro, there is no difference in phagocytic activity and organelle motility in PM from S and NS. PMID- 2311742 TI - Influence of hypercapnia on rabbit intrapulmonary neuroepithelial bodies: microfluorimetric and morphometric study. AB - The present investigation was undertaken to investigate the influence of hypercapnia on intrapulmonary neuroepithelial bodies (NEB). Rabbits were mechanically ventilated with a hypercapnic gas mixture (7% carbon dioxide, 20% oxygen, 73% nitrogen). Lung samples were examined by a microspectrographical analysis of the NEB formaldehyde-induced fluorescence to quantify the cytoplasmic 5-hydroxy-tryptamine (5HT) content and by electron microscopy to determine morphometrically the extent of the secretory exocytosis at the basal poles of the NEB epithelial cells. In contrast to our earlier studies on the effects of hypoxia and/or vagal stimulation, hypercapnia did not alter significantly the NEB cytoplasmic fluorescence nor did it affect the corpuscular epithelial exocytosis. NEB appear not to be influenced by hypercapnia to discharge their contents of 5HT and peptides. This investigation appears to support a high selectivity of the intrapulmonary NEB to local hypoxia and changes in vagal efferent output. PMID- 2311743 TI - Revaccination with BCG: its effects on skin tests in Kuwaiti senior school children. AB - Following a policy of BCG vaccination adopted in Kuwait more than 20 yrs ago, children receive their first vaccination just before starting school. Those who have a response of less than 10 mm induration to 2 tu of RT23 PPD, when they are 13 yrs old, are revaccinated. The effects of this revaccination on skin test positivity in a group of 18 yr old senior school children have been investigated. In a random study group 23% were found to have received BCG a second time. Revaccination resulted in a significant increase in positivity to tuberculin, and to the other 6 reagents tested, that was much more than would have been expected due to the passage of time alone in low responders. Scars of the second BCG vaccination were larger than those after the first vaccination, and showed a sex difference, with scars being significantly larger in boys than in girls. Boys also tended to show the largest responses to skin tests, with the notable exception of tuberculin to which girls showed the largest response. In most cases responses to skin tests were larger after revaccination than after a single vaccination. Based on this study, it is impossible to be sure that revaccination improved protective immunity, but the increase in tuberculin responsiveness, and recognition of environmental mycobacterial species may be indirect evidence supporting this conclusion. PMID- 2311744 TI - Skeletal muscle metabolites and fibre types in patients with advanced chronic obstructive pulmonary disease (COPD), with and without chronic respiratory failure. AB - Eighteen patients with advanced COPD, 8 with chronic respiratory failure (RF) and 10 without (nonRF, NRF) were investigated using spirometry, arterial blood gas analysis and biopsies taken from the quadriceps femorls muscle. The biopsies were analysed for ATP, creatine phosphate (CrP), creatine (Cr), lactate and glycogen content. Muscle fibre composition was also studied. Low concentrations of ATP, glycogen and CrP were found in the RF patients. Significant correlations were found between muscle metabolites and arterial blood gas values with the strongest correlation between muscle glycogen and arterial PO2 (r = 0.70; p less than 0.001). A very low percentage of "oxidative" type I muscle fibres was found in both groups. Possible mechanisms causing depletion of muscle metabolites are discussed. PMID- 2311745 TI - Can a single equation be used to predict the vital capacity of boys both before and during puberty? AB - Good theoretical values for vital capacity (VCt) can be used to calculate a VC/VCt ratio which remains constant for a given individual subject throughout different growth periods. This longitudinal study on 27 boys was performed in order to determine whether a single equation was accurate throughout the growth of boys. The mean values of VC/VCt were also compared for the beginning and end of the prepubertal period in 57 boys and between the beginning and end of puberty in 40 boys. VCt was calculated from five reference equations using data from boys with average age 8-16 yrs, and from two equations using data specific to children and adolescents. The mean VC/VCt ratio was found to fall between the beginning and end of the prepubertal period and to increase very significantly between the beginning and end of the pubertal period when the reference equation used had been calculated using data from populations containing both pubertal and prepubertal subjects. When the equations established from adolescents were used, VC/VCt fell slightly between the beginning and end of the pubertal period. We conclude that data for children and adolescents should be treated separately when establishing reference values for VC. PMID- 2311746 TI - Ofloxacin in miliary tuberculosis. AB - We report one case of severe miliary tuberculosis with liver failure and respiratory insufficiency in a twenty-seven year old patient. We emphasize the presence of hepatic, occular and vestibular toxicities secondary to the treatment and the usefulness of ofloxacin with cycloserine given for nine months. PMID- 2311748 TI - Isolated cough which responds to inhaled salbutamol and beclomethasone dipropionate. PMID- 2311747 TI - Human pulmonary infection with Corynebacterium equi. AB - A 28 year old man with no underlying disease developed a cavity and multiple nodules in the lung from which Corynebacterium equi was isolated. He experimented with organic solvents and microorganisms including Corynebacterium species for several years. Computed tomography of his pulmonary lesions revealed that these nodules were related to the bronchial tree. Histologically, the lesions were compatible with nonspecific inflammatory changes. The clinician must suspect the pulmonary infections with Corynebacterium species even if the patient has no underlying disease. PMID- 2311749 TI - Culturally sensitive family assessment: an evaluation of the family assessment device used with Hawaiian-American and Japanese-American families. AB - This article reports the results of a study of the McMaster Family Assessment Device (FAD) used with samples drawn from two non-Anglo ethnic groups: Hawaiian Americans and Japanese-Americans living in Hawaii. The results showed that the FAD appeared to make appropriate assessments of Hawaiian-American study participants' families and inappropriate assessments of Japanese-American study participants' families. Results also suggested that cultural norms regarding family functioning may vary according to socioeconomic status. FAD modifications are suggested. PMID- 2311750 TI - Mind-body problems in family therapy: contrasting first- and second-order cybernetics approaches. AB - Using detailed case examples, we contrast first- and second-order cybernetics approaches to family problems involving somatic symptoms in a family member. A second-order cybernetics approach views the reality of the problem as linguistically shaped by those interacting around it, including the therapist and observing team members. This co-constructed reality, the story of the problem, inadvertently contributes to the problem's endurance by narrowing the choice of more effective solutions. In our approach, the therapist elicits from each person his or her story about the illness in the family. The therapist then facilitates a therapeutic conversation that provides a context for new linguistic distinctions to be drawn, including the way mind and body may interact to generate the symptoms. Shifts in beliefs and behaviors follow, and more innovative solutions to the problem can then emerge. Unlike the approach in our previously published work based upon ecosystemic patterns as "system diagnoses," this approach uses only descriptions and explanations of the problem as are collaboratively constructed within this therapeutic conversation. PMID- 2311751 TI - Patterns of learning in family therapy training. AB - This study presents the results of an evaluation of two cohorts of trainees who had completed a 2-year training program in family therapy. The 15 trainees were assessed in the areas of perceptual/conceptual, intervention/executive skills and personal development both pre- and post-training. Although the group results showed skill acquisition in all areas assessed, the individual results revealed a complexity in performance glossed over by the group analysis. Trainees' learning commenced from different baselines, advanced at different rates, and there was a marked discrepancy between self-reports of improvements (or otherwise) and the results of the observer-rated measures. We recommend that increasing attention be paid to individual differences in learning styles in training and in evaluation. PMID- 2311752 TI - Do better trainees make worse family therapists? A followup study of client families. AB - This study was designed to evaluate the effects of training on family therapy outcome and to validate measures of cognitive/perceptual and executive skills. Followup data on family satisfaction were obtained from 176 individuals (73 families) treated by 12 trainee family therapists in their first or second year of training. The prediction that clients' scores on a scale of family satisfaction with therapy (FSS) would increase with training was not confirmed. Instead, there was a tendency for FSS scores to decrease with training. However, trainees' ratings of outcome did increase significantly as training progressed. Cognitive/perceptual and executive skill measures were not validated by the FSS, but negative associations indicated a tendency for trainees with high course skills to receive poor FSS scores. The results suggest that trainees became more confident as they acquired technical skills, but that they put aside their nonspecific therapist skills as training progressed, to the dissatisfaction of families. PMID- 2311753 TI - Contextual therapy: brief treatment of an addict and spouse. AB - The clinical and theoretical applications of contextual therapy for the treatment of drug abuse are presented. A case study illustrates intervention strategies, the therapy process, and a contextual-intergenerational view of drug addiction. Contextual concepts of intergenerational processes, loyalty, fairness, accountability, and trust are defined and applied. Four stages of brief contextual therapy are presented, and the process is examined using examples from transcribed transactions of the therapy sessions. It is suggested that contextual therapy offers conceptual and methodological tools for working with complex situations often involved in drug abuse cases. PMID- 2311754 TI - Focal family therapy: theory and practice. AB - During the past 30 years, the prescription of neuroleptic medication has made a major impact on the treatment of symptoms in patients with schizophrenia. Nonetheless, for many patients, symptom remission and social functioning remain less than optimal. Consequently, clinicians have employed a combined approach of drugs, psychosocial therapies, and psychiatric rehabilitation to treat the range of deficits presented by individuals suffering with this illness. In this article, we describe Focal Family Therapy, a model of family therapy developed for working with families and patients who are struggling with schizophrenia. Using the example of a particular case, we illustrate the following: (a) the identification and formulation of the Focal Issue; (b) the targeting of behavior and attitudes that will constitute the Focal Change; and (c) the techniques of Focal Family Therapy. PMID- 2311755 TI - The effect of being reared with an alcoholic half-sibling: a classic study reanalyzed. AB - Data from an early study of alcoholism among half-siblings of alcoholic probands (17) was reanalyzed using log-linear analysis. The original study, which used chi square analysis, identified genetic factors but found no environmental effects that contributed to the prediction of alcoholism. Log-linear analysis, however, reveals that being reared with a proband is associated with a reduced incidence of alcoholism in half-siblings. The results do not disconfirm the presence of genetic factors, but they do indicate that family dynamics make an independent and statistically significant contribution to the development of alcoholism not heretofore demonstrated. Similarities between these results and the results from studies of identical twins are discussed. PMID- 2311756 TI - Convergent and discriminant validity of FACES-III: family adaptability and cohesion. AB - Research on earlier versions of the Family Adaptability and Cohesion Evaluation Scales (FACES) has ostensibly shown that the scales lack discriminant and convergent validity (23). However, these studies have defined convergence as agreement between family members or as agreement between family members and family therapists. Such definitions confound real differences between respondents' perceptions of the family with the notion of convergent validity. In the current study, we take a different approach to construct validity. Multiple measures of family adaptability, cohesion, and talkativeness were administered to two family members (insiders) and two significant others (outsiders). The two insiders' responses were averaged together, as were the two outsiders' responses. Using confirmatory factor analysis, we demonstrated that family adaptability, cohesion, and talkativeness are distinct traits, and that the different sources of information about these traits, including FACES-III (24), have convergent validity. PMID- 2311757 TI - Characterization of a cytotoxin-like basic protein from the cobra (Naja naja naja) venom. AB - A cytotoxin-like basic protein has been isolated from the venom of the nominate race of cobra (Naja naja naja from Pakistan) by a single step of high-performance liquid chromatography. The primary structure was determined and consists of 62 amino acid residues in a single polypeptide chain. It is highly similar to that of the cytotoxin-like basic proteins isolated from other Naja species, but differs in two of the SS-loop structures from that of cytotoxins. PMID- 2311758 TI - Effect of the multicatalytic proteinase (prosome) on translational activity in rabbit reticulocyte lysates. AB - In a message-dependent reticulocyte lysate translation system, incorporation of [3H]leucine into acid-insoluble protein is increased following selective removal of the multicatalytic proteinase (MCP) with a monospecific antibody. Re-addition of active proteinase to previously depleted lysates reverses this effect in that the same low levels of translational product are measured as in untreated lysates. Addition of histone-stimulated MCP further depresses the level of protein product. Conversely, lysates supplemented with inactivated MCP retain the higher level of translational activity which is measured after precipitation of the enzyme with antibody. In these lysates, the effect of the antibody on translational activity is inversely correlated with that on hydrolytic activity towards [14C]methylcasein or N-succinyl-Leu-Leu-Val-Tyr-4-methyl-7-coumarylamide, two substrates of the MCP. These results showing that the MCP is capable of modulating translational activity in vitro, suggest an important role of this molecule in the in vivo translational process. PMID- 2311759 TI - Expression of the pS2 gene in human gastric cancer cells derived from poorly differentiated adenocarcinoma. AB - NH2-terminal amino acid sequence of the pS2 protein produced and secreted by human gastric cancer cells, MKN-45, was determined to be identical to that of MCF 7 cells. A clone encoding pS2 protein was isolated from the cDNA library constructed from MKN-45 cells. The nucleotide sequence was identical to that of pS2 cDNA previously isolated from human breast cancer cells, MCF-7, except for one nucleotide in the 3' untranslated region. Thus, in this cell line, the pS2 gene product is translated and secreted as in MCF-7 cells. RNA blot hybridization analysis revealed that pS2 gene was expressed well in two (MKN-45 and KATO-III; derived from poorly differentiated adenocarcinoma) but not in three cell lines (MKN-1, MKN-28 and MKN-74; from well differentiated adenocarcinoma), suggesting that expression of the pS2 gene depends on the state of cell differentiation. These results suggest that pS2 is expressed in human gastric cancer cells in an estrogen-independent manner and is possibly associated with the malignant state of cells. PMID- 2311760 TI - Rapid up- and down-regulation of hexokinase II in rat skeletal muscle in response to altered contractile activity. AB - An up to 14-fold increase in total hexokinase activity induced by low-frequency stimulation in rat fast-twitch muscle was followed by a rapid decay in enzyme activity after cessation of stimulation. In vivo labeling revealed that these alterations were related to rapid changes in [35S]methionine incorporation into hexokinase II. A recovery period of 15 h after cessation of stimulation was sufficient to normalize the approximately 30-fold elevated [35S]methionine incorporation. PMID- 2311761 TI - Ca2(+)-dependent noradrenaline release from permeabilised PC12 cells is blocked by botulinum neurotoxin A or its light chain. AB - Permeabilisation of PC12 cells with digitonin allowed a direct study of the intracellular action of botulinum neurotoxin A, one of a group of dichain proteins produced by Clostridium botulinum that causes the fatal neuroparalytic condition, botulism. Release of [3H]noradrenaline from these permeabilised cells could be evoked by Ca2+ and this was inhibited specifically by the neurotoxin in a dose-dependent manner (half-maximal dose approximately 2 nM under the conditions used). Inclusion of the reducing agent dithiothreitol (up to 10 mM) had no effect on the level of inhibition. Moreover, electrophoretic analysis showed that this treatment of the toxin in the native state caused negligible reduction of inter-chain disulphide bonds. Toxin-induced blockade of neurotransmitter release was incomplete and could not be overcome by increased Ca2+ concentration (100 microM). The observed toxin-insensitivity of the release from intact PC12 cells must result from inefficient toxin uptake, relative to that in peripheral cholinergic neurones. Refolded light chain alone inhibited exocytosis to the same degree and with similar potency to that of the intact neurotoxin, an effect not altered by the heavy chain. This inhibitory activity of the light chain in PC12 cells accords with observations made in permeabilised chromaffin cells [(1989) J. Biol. Chem. 264, 10354-10360; (1989) FEBS Lett. 255, 391-394] but contrasts with invertebrate neurones, where intracellular injection of the same preparations of both chains were necessary for inhibition of quantal release of acetylcholine [(1988) Proc. Natl. Acad. Sci. USA 85, 4090-4094]. These collective findings may signify an interesting difference in the release process in such diverse systems or denote a dissimilarity in the transport or processing of the toxin when applied into intact neurones or cells permeabilised by detergent or streptolysin. PMID- 2311762 TI - CD4-like molecules in human sperm. AB - The expression of a molecule recognized by CD4 monoclonal antibodies was investigated on human sperm using immunolabelling, biochemical and immunochemical methods. Flow cytometry detected a significant fluorescence signal. SDS-PAGE analysis and Western blotting identified a molecule of 60 kDa, consistent with a CD4-like structure as confirmed after selective immunoseparation. Additional bands reacting with anti-CD4 were found in sperm extracts (73 kDa) and seminal fluid (90 kDa). These data indicate that sperm express a molecule similar to the receptor for HIV described on mononuclear cells. PMID- 2311763 TI - ADP-ribosylated elongation factor 2 (ADP-ribosyl-EF-2) is unable to promote translocation within the ribosome. AB - Elongation factor 2 (EF-2), ADP-ribosylated in vitro by the A-fragment of diphtheria toxin, can (in the presence of GMPPCP) form stable complexes with ribosomes regardless of whether the ribosomes are empty or carrying poly(U) and Phe-tRNA in the A-site. Despite its efficient binding to ribosomes, ADP-ribosyl EF-2, in contrast to the non-modified EF-2 is unable to promote the shift of Phe tRNA from the A-site to the P-site of the ribosome as determined by the puromycin reaction, i.e. it is incapable of promoting the translocation reaction within the ribosome. PMID- 2311764 TI - Protein chemical analysis of purified murine lamin B identifies two distinct polypeptides B1 and B2. AB - Lamin B purified from murine EAT cells was characterized by partial protein sequences. Contrary to the current view that mammals express only a single lamin B polypeptide corresponding to a characterized murine cDNA clone, our analysis documents two distinct B lamins. One protein follows the established cDNA sequence while the other identifies a novel murine lamin B. Comparison with the two chicken lamin B sequences established by cDNA cloning identifies the first murine lamin B sequence as a B1 type and the second as a B2 type. We conclude that mammals express two distinct lamin B forms as established by others for chicken. PMID- 2311765 TI - Rapid increase in inositol pentakisphosphate accumulation by nicotine in cultured adrenal chromaffin cells. AB - When [3H]inositol-prelabeled cultured bovine adrenal chromaffin cells were stimulated with nicotine (10 microM), a large and transient increase in [3H]inositol pentakisphosphate (InsP5) accumulation was observed. The accumulation reached the maximum level at 15 s, then declined to the basal level at 2 min. Nicotine also induced [3H]inositol tetrakisphosphate (InsP4) and [3H]inositol hexakisphosphate (InsP6) accumulation with a slower time course and a lesser magnitude than [3H]InsP5. The peaks of [3H]InsP4, [3H]InsP5 and [3H]InsP6 coincided with those of 32P radioactivity, when cells were doubly labeled with [3H]inositol and inorganic 32P. These results suggest that inositol pentakisphosphate is rapidly increased by nicotine, a cholinergic agonist, in cultured adrenal chromaffin cells. PMID- 2311766 TI - Locustatachykinin I and II, two novel insect neuropeptides with homology to peptides of the vertebrate tachykinin family. AB - Two myotropic peptides termed locustatachykinin I (Gly-Pro-Ser-Gly-Phe-Tyr-Gly Val-Arg-NH2) and locustatachykinin II (Ala-Pro-Leu-Ser-Gly-Phe-Tyr-Gly-Val-Arg NH2) were isolated from brain-corpora cardiaca-corpora allata-suboesophageal ganglion extracts of the locust, Locusta migratoria. Both peptides exhibit sequence homologies with the vertebrate tachykinins. Sequence homology is greater with the fish and amphibian tachykinins (up to 45%) than with the mammalian tachykinins. In addition, the intestinal myotropic activity of the locustatachykinins is analogous to that of vertebrate tachykinins. The peptides discovered in this study may just be the first in a whole series of substances from arthropod species to be identified as tachykinin family peptides. Moreover, both chemical and biological similarities of vertebrate and insect tachykinins substantiate the evidence for a long evolutionary history of the tachykinin peptide family. PMID- 2311767 TI - Binding of GTP to transducin is not inhibited by arrestin and phosphorylated rhodopsin. AB - In the presence of a photobleaching intermediate of unphosphorylated or phosphorylated rhodopsin (Rh*), the binding of GppNHp to transducin was measured with or without arrestin for elucidation of the shut-off mechanism of the visual transduction process in bovine rod outer segments. The ability of Rh* to catalyze the formation of the transducin-GppNHp complex in the absence of arrestin was independent of the degree of phosphorylation of Rh*. Furthermore, the catalyzing ability of the phosphorylated Rh* was not reduced by the addition of arrestin. These observations indicate that the interaction between phosphorylated Rh* and transducin was not inhibited by arrestin. Thus, the hypothesis was not supported that the PDE shut-off process is a simple competition between transducin and arrestin for binding to phosphorylated Rh*. PMID- 2311768 TI - Primary structure of scorpion anti-insect toxins isolated from the venom of Leiurus quinquestriatus quinquestriatus. AB - The amino acid sequences of insect-selective scorpion toxins, purified from the venom of Leiurus quinquestriatus quinquestriatus, have been determined by automatic phenyl isothiocyanate degradation of the S-carboxymethylated proteins and derived proteolytic peptides. The excitatory toxin Lqq IT1 and Lqq IT1' (70 residues) show the shift of one half-cystine from an external position, which is characteristic of anti-mammal toxins, to an internal sequence position. Lqq IT2 (61 residues) displays the half-cystine residue in position 12, common to the sequence of all known anti-mammal toxins; it induces flaccid paralysis on insects but is non-toxic for the mouse. Lqq IT2 structurally defines a new type of anti insect toxins from scorpion venoms. CD spectra and immunological data are in agreement with this finding. PMID- 2311769 TI - A conserved cleavage-site motif in chloroplast transit peptides. AB - A collection of 32 stroma-targeting chloroplast transit peptides with known cleavage sites have been analysed in terms of amino acid preferences in the vicinity of the processing site. A loosely conserved consensus motif (Val/Ile)-X (Ala/Cys) decreases Ala is found in the majority of the transit peptides. About 30% of the sequences have a perfect match to the consensus. When such a match is found, there is a 90% probability that it specifies the correct cleavage site. PMID- 2311770 TI - Unit-based phase I cardiac rehabilitation program for patients with myocardial infarction. PMID- 2311771 TI - Active recruitment could make a difference. PMID- 2311772 TI - Organization, design, and implementation of an interventional cardiology patient care unit. AB - We have described the major steps required to open a new ICPCU. The unit allows for a comprehensive standardized approach to the education of patients undergoing interventional cardiology procedures and offers the optimal setting for nursing research in the field of interventional cardiology and cardiovascular nursing. Primarily, the advent of this unit has supported the implementation of primary nursing, allowed for optimal continuity of patient care, and contributed to a decrease in the length of hospital stay of these patients and an increase in patient and family satisfaction. PMID- 2311773 TI - Extracorporeal membrane oxygenation in adults: a nursing challenge. AB - ECMO is an aggressive treatment for selected patients who are unresponsive to conventional therapy for respiratory failure. Although its use in neonates is well documented, the number of successful reports in adults is limited. Venovenous ECMO represents a therapeutic option for adult patients with severe respiratory failure that has not responded to diuresis, high oxygen flows, and positive end-expiratory pressure. As medical centers obtain more experience with and resources for adult ECMO, critical care nurses will need to develop more familiarity with this technology. PMID- 2311774 TI - Dark hours. PMID- 2311775 TI - Against nursing advice? PMID- 2311776 TI - Cardiovascular complications of intravenous vasopressin therapy. PMID- 2311777 TI - The professional imperative: research utilization in the search for scientifically based nursing practice. PMID- 2311778 TI - Families in critical care: what do they really want? PMID- 2311779 TI - Cultural competence: nursing faces imperative challenge. PMID- 2311780 TI - A tribute to African American nurses. PMID- 2311781 TI - Consider facts, not myths about aging population. PMID- 2311782 TI - Cultural factors play role in pediatric assessment. PMID- 2311783 TI - Florida's isolated rural elderly: a subculture of its own. PMID- 2311784 TI - 1986 research grant. PMID- 2311785 TI - How is the validity of a research instrument (questionnaire, test, etc) determined? PMID- 2311787 TI - America's biomedical research enterprise: building the bridge to a better future. PMID- 2311786 TI - Antiphospholipid antibodies in systemic lupus erythematosus. PMID- 2311788 TI - [Patients born in autumn more frequently develop atopic eczema]. AB - Data of birth from 4040 atopic dermatitis patients born in the Berlin area were analyzed in view of their distribution over the 12 months of the year. For comparison the data of birth of all people being born during two years were treated the same way. There was a marked increase of atopic dermatitis with the persons born during the months August to October. On the other hand, the prevalence of atopic dermatitis was diminished with that persons who were born from February till July (with exception of May). Obviously, during the first months of life seasonally differing external factors influence directly o indirectly the decision, whether atopic dermatitis later on will manifest or not. These results should been taken into consideration for family planning in high risk families. PMID- 2311789 TI - [Diagnosis and clinical relevance of microcirculation disorders in progressive scleroderma]. AB - Microcirculation in the hands of patients with progressive systemic sclerosis shows some peculiarities. For diagnostic purposes functional thermography and the acrale rewarming test may be used. Typical features of progressive systemic sclerosis are a general hypothermia of the hands and localized hypothermic areas and refractory hyperthermic areas. In the acrale rewarming test reactive vasodilatation after cold stimuli is often not inducible and the significantly retarded rewarming shows a marked local restrict dependence. The significance of these facts for a more intensive physical therapy is discussed. PMID- 2311790 TI - [Forensic value of morphologic-morphometric sperm differentiation in the study of stains. II: Use in criminal practice]. AB - On the basis of the results gained by applying the morphologic-morphometric sperm differentiation in 42 cases of sexual offence 36 individuals could not be excluded as the source of sperm traces (36 criminal offences with 105 sperm traces). Another 100 individuals wer excluded as the source by means of the comparative sperm test. The influence of exogenic and endogenic factors on the sperm image has been discussed, especially in the context of the criminal orientated problem. Thus, possible changes of the analysable sperm image may be recognized in the ejaculate and, consequently, in the sperm trace in time relation to the effect of a harmful event only after several weeks up to months. PMID- 2311791 TI - [Relation between the anti-oxidative potential of psoriasis blood plasma in reactivity of granulocytes]. AB - It was revealed a positive correlation between an antioxidative potential (AP) of blood plasma from psoriasis patients and generation of O2- by normal granulocytes, stimulated by zymosan or aggregated human gamma-globulin, in the presence of the same plasma samples. The AP of plasma was measured by means of inhibition of the chemiluminescence arising during photoautoxidation of luminol. The production of O2- after cell stimulation was estimated by means of the reduction of tetrazolium salt. The result is discussed from the viewpoint of informative-regulatory role of the plasma AP for the white blood cells as a part of the whole organism, participating in its common defence reactions. PMID- 2311792 TI - [Prolonging transplant survival time by PUVA treatment of the transplant recipient. Significance of cis-urocanic acid]. AB - A PUVA treatment of the recipients of murine tail skin grafts led to a significant prolongation of transplant survival. A possible mechanism of the systemic immunomodulatory effects of ultraviolet light in the organism is the transformation of urocanic acid in the skin from its trans- to the cis-isomer, which acts as a mediator on the immune system. A treatment of graft recipients with cis-, but not trans-urocanic acid also prolonged graft survival. The rejection of secondary grafts and the humoral immune response of mice to sheep erythrocytes were not influenced by cis-urocanic acid. These results implicate that cis-urocanic acid may be get use in clinical organ transplantation and dermatology. PMID- 2311793 TI - [Sclerodermia bullosa and diabetes mellitus. A case report]. AB - Our case is dealing with a very rare combination of sclerodermia bullosa with diabetes mellitus. Ulceration and secondary bacterial infection appeared as a complication. The possible pathophysiological mechanisms which may influence this unusual coindidence are discussed in the paper. PMID- 2311794 TI - Topical ciclosporin in nail psoriasis. PMID- 2311795 TI - Urinary tract desquamation in psoriasis. PMID- 2311796 TI - Alopecia areata: more on topical sensitizers. AB - Our experience on treating alopecia areata with topical sensitizers (diphencyprone, squaric acid dibutylester) is reported: staging, prognosis, side effects, follow-up, and psychological attitude of the patients towards this therapy and wigs are the focused aspects. The possible mechanisms of action of these allergens are discussed, reporting the case of a female patient with concomitant appearance of hair regrowth and psoriatic plaques in the same area after SADBE therapy. PMID- 2311797 TI - Transepidermal potassium ion, chloride ion, and water flux across delipidized and cellophane tape-stripped skin. AB - The skin barrier was evaluated as a function of transepidermal water loss (TEWL) and electrolyte loss. Combination electrodes for chloride and pH determinations and a potassium ion electrode were utilized. Delipidization of the skin did not impair the electrolyte barrier, but did damage the epidermal water barrier. Cellophane tape stripping of normal stratum corneum resulted in an increase in outward transepidermal potassium and chloride ion flux, an increase in skin surface pH, and an increase in TEWL. It appears that damage to the epidermal water barrier does not necessarily result in damage to the epidermal electrolyte barrier. We found the potassium electrode facile to use and believe that a combination potassium electrode would be useful for investigating and assessing the epidermal electrolyte barrier. PMID- 2311798 TI - HLA-DR and 96-K antigens and intratumoral lymphocytic infiltrate in primary cutaneous melanoma as markers of tumor progression. AB - It was recently demonstrated that HLA-DR antigens in primary melanomas are correlated with 96-K antigen expression and with the presence of an intratumoral lymphocytic infiltrate (ILI). As HLA-DR antigens are known to be associated with advanced phases of tumor progression in melanocytic lesions, we investigated whether primary melanomas in different progression phases could be distinguished on the basis of the expression of HLA-DR and 96-K antigens and of the presence of an ILI. A concordant presence of the two antigens and of an ILI was frequent both in vertical growth pattern melanomas and in melanomas thicker than 1 mm. On the contrary, both antigens and the ILI were frequently absent both in thin melanomas (less than 1 mm) and in radial growth pattern melanomas. These observations suggest that a joint study of HLA-DR and 96-K antigens and of the ILI is useful to define the phase of progression of primary melanomas. PMID- 2311799 TI - Prevalence of Ureaplasma urealyticum in the urethra of men without urethritis in relation to clinical diagnosis. AB - Ureaplasma urealyticum is one of the microorganisms possibly causing nongonococcal urethritis. In a prospective study, 606 men without urethritis presented to an STD clinic in a rural West German region were investigated for the prevalence of U. urealyticum in the urethra. The overall isolation rate of the organism was 21.3%. Analyzing patients grouped by clinical diagnoses, the isolation rate of U. urealyticum was significantly higher in the genital warts group (25%) and in the partner's control group (35%) than in the group of patients suffering from fertility disorder (15.2%) or balanitis (14%). These findings stress the importance and the difficulty to select the appropriate controls in clinical studies concerning the role of U. urealyticum in the male urethra. PMID- 2311800 TI - Subclinical dilatation of dermal sweat ducts. AB - 1,323 biopsied skin specimens were retrospectively investigated. Dilatation of dermal sweat ducts was observed in 18 specimens (1.36%). They included 7 specimens of malignant and benign neoplasms or nevi, 5 of fibrosis and 6 of various inflammations. The face was the favored site, but it was also seen in other areas. Ten out of 18 specimens were taken in the summer. It was speculated that the massive secretion of sweat and the compression of sweat ducts by several tissue components in the dermis played an important role for the dilatation of the sweat ducts. PMID- 2311801 TI - RAST and PRIST in children with atopic dermatitis. AB - The study was carried out in 535 children. The frequency of positive RAST for food allergens decreased with age, whereas the frequency of positive RAST for inhalant allergens increased with age. Coexistence of asthma and/or rhinitis was not related to the results of RAST with food allergens. Positive RAST and multiple sensitivity for inhalant allergens were significantly greater in children with coexistence atopic respiratory disease. Total IgE was significantly higher in children with coexistent atopic respiratory disease in all age groups. This study provides information for the critical analysis of a RAST in atopic dermatitis. PMID- 2311802 TI - A case of quadrantic capillaropathy. AB - A case of transient pigmented purpuric dermatosis in an unusual segmental distribution is presented, and possible aetiological factors discussed. PMID- 2311803 TI - Bilateral squamous cell carcinomas arising in long-standing necrobiosis lipoidica. AB - We describe the second case of bilateral squamous cell carcinoma arising in long standing necrobiosis lipoidica. The occurrence of squamous cell carcinoma in necrobiosis lipoidica is rare, but should be considered in recalcitrant ulcers, especially when infiltrated. PMID- 2311804 TI - A case of delayed hypersensitivity reaction following a sea urchin sting. AB - The case of a 28-year old woman with pruritic and erythematous eruptions on the knees and ankle about 10 days after being stung by sea urchin is reported. The spines of a sea urchin were ground, extracted and patch-tested, to which the patient showed a positive delayed skin reaction. Based on the clinical course and positive patch tests, it was concluded that the patient developed a delayed hypersensitivity reaction to the sea urchin's stinger. PMID- 2311805 TI - Outcome of triplet pregnancies resulting from IVF at Bourn Hallam 1984-1987. AB - 43 consecutive sets of triplet pregnancies progressing beyond 16 weeks and conceived following in vitro fertilisation at the Bourn Hallam Centre between 1984-1987 were included in the study. Follow-up information was available in the 31 sets born to United Kingdom residents. 91 live births resulted at an average gestation of 33 weeks and 2 days (range 26-38 weeks). All but one of the deliveries was by Caesarean section. The average birth weight was 1.85 kg and was significantly higher in the first-born triplet than in the third (1.93 kg versus 1.74 kg, respectively). The perinatal mortality rate amongst the triplets was 32.26 per thousand births, and the neonatal death rate was 21.98 per thousand live births. This compares favourably with the latest published data on perinatal mortality rates in triplets. PMID- 2311806 TI - Maternal opinion about analgesia in labour and delivery. A comparison of epidural blockade and intramuscular pethidine. AB - In a prospective randomized study we evaluated the opinion of 97 parturients on either epidural analgesia or parenteral pethidine with respect to analgesic efficacy, general feelings and symptoms during labour and delivery. The analgesic effect of the epidural block was significantly superior to pethidine with regard to the pain score (visual analogue scale (VAS)0 during the first stage of labour (mean VAS 11 contrasting 65). Moreover, 30 (59%) women in the epidural group compared to 9 (20%) in the pethidine group had a painless labour and delivery. Significantly more parturients (37 (73%)) in the epidural group would request an epidural blockade rather than pethidine treatment (14 (30%)) in a subsequent labour. Fewer side effects were registered in the epidural group compared to the pethidine group, however only significantly concerning sleepiness. It is concluded that in this study low-dose epidural analgesia during the first stage of labour was superior to parenteral pethidine regarding pain relief and side effects. PMID- 2311807 TI - Conservative management of fetal bigeminy arrhythmia leading to persistent bradycardia. AB - A case of persistent fetal bradycardia first detected at 32 weeks of gestational age is described. The diagnosis of atrial ectopic beats was made by means of M mode echocardiography. Since the fetus was normally grown and showed no signs of distress, the vaginal route of delivery was allowed, also because continuous M mode echocardiographic monitoring was possible during labour. PMID- 2311808 TI - Premature rupture of the membranes and amniotic infections--the significance of laboratory tests. AB - White blood cell count (WBC), C-reactive protein (CRP) and elastase alpha 1 proteinase inhibitor complex (E alpha 1 PI) have been determined in 85 women during pregnancy and after birth to assess their diagnostic value in case of amniotic infection syndrome (AIS). In ten patients clinically diagnosed AIS could be confirmed by histopathological examination, five patients who fulfilled the clinical criteria showed no histological signs of infection. E alpha 1 PI levels were found to be elevated to above 200 micrograms/l in nine patients with clinical and histological infection and remained below this value in all but one of the cases not showing signs of AIS. On the other hand, CRP concentrations were elevated in five out of these ten women, but also showed false-positive values in patients without AIS; leucocyte counts above 15,000/mm3 have been observed in only one case before delivery. The application of betamethasone led to a marked elevation of leucocyte concentrations. CRP levels were raised substantially after birth, whereas E alpha 1 PI remained unchanged under both conditions. It is suggested that all three parameters should be taken into consideration to increase diagnostic reliability in case of suspected amniotic infections. PMID- 2311809 TI - Comparison of four different dosages of injectable bromocriptine retard for puerperal ablactation. AB - The clinical efficacy, tolerance and effect on plasma prolactin levels of four different dosages of intramuscular bromocriptine retard were compared. 108 Chinese puerperas with a mean body weight of 58 kg, who chose not to breast-feed following vaginal delivery, were randomized into four equal groups. The patients in each group were given intramuscular bromocriptine retard: 20, 30, 40 or 50 mg. The injection was well tolerated by all, except for two patients who developed small haematomas at the site of the injection and 2 patients who complained of dizziness. Ablactation occurred in 100% of the patients in the 40 mg group, but was successful in only 92 and 91% of the patients in the 20 and 30 mg groups, respectively. There were two cases of suboptimal response in the 50 mg group, despite marked reduction in plasma prolactin levels. Both these patients had developed moderate breast engorgement before they received the injection. The difference in response among the four groups was not statistically significant. We recommend that the injection be given prior to the development of breast engorgement. PMID- 2311810 TI - Efficacy, safety and tolerance of oral sustained-release ritodrine given after intravenous administration in the treatment of premature labor. AB - 45 patients in premature labor entered the study, four dropped out for administrative reasons. The remaining 41 patients started all with an intravenous treatment followed by oral treatment with sustained-release ritodrine at a daily dosage of 120 mg per day until the 36th week of gestation. The mean gestational age at entry was 31.26 weeks +/- 3.27 and at delivery 37.76 weeks +/- 2.11 or a mean gain in days of 44.61 days +/- 20.85. A cluster analysis splitting the patients into four groups regarding the gestational age at entry and the Baumgarten tocolytic index showed that even the high-risk patients benefit remarkably by the treatment. The side effect rate was low as well for palpitation as for tremor. The patient compliance was excellent. No neonatal deaths or stillborns occurred during this study. PMID- 2311811 TI - Evaluation of variable decelerations of fetal heart rate with the deceleration index: influence of associated abnormal parameters and their relation to the state and evolution of the newborn. AB - The deceleration index of the Fetal heart rate (FHR) (Acien P. et al. (1979) J. Perinat Med 7, 7-18) was used to analyze 157 cardiotocographic registers that displayed variable deceleration during labor. We have related the deceleration index value to perinatal results and to other abnormal parameters of FHR. An increase in neonatal pathology was observed in the deceleration group compared to a group of 50 controls with normal FHR, when the deceleration index was greater than 150 and specially if it was greater than 200. The association of other abnormal parameters of FHR (especially absence of variability between or during decelerations, absence of transitory ascents, presence of tachycardia and, of less importance, absence of ascents at the beginning of deceleration or presence of overshoot acceleration following deceleration) yields a worse prognosis for the fetus than does an increased deceleration index alone. The deceleration index is a good method for evaluation of variable decelerations of FHR, and is well correlated to the condition of the newborn. PMID- 2311812 TI - Biomechanical analysis of human chorioamniotic membranes. AB - The biomechanical properties of human fetal membranes were analyzed by means of a materials testing machine. Special attention was paid to the biomechanical properties of the intact chorioamniotic membrane and the amniotic and chorionic components, separately, and thickness and storage of membrane samples. The load strain and stress-strain relationships, and parameters calculated from the curves: extensibility, strength, elastic stiffness and failure energy, express the visco-elastic behavior of these membranes. The mechanical properties of the chorioamniotic membranes are determined by the interaction between the amniotic and chorionic components of the membrane. The strength of the intact chorioamniotic membrane, however, is primarily determined by the amniotic component, because the amniotic component is much less extensible. Thus, the chorionic component only contributes 10-15% of the strength when the amniotic component breaks. The chorionic component is twice as extensible as the amniotic component. Samples of fetal membranes can be stored at -70 degrees C, with no significant changes in the biomechanical properties. No significant differences were found between specimens, which were oriented in parallel with and at right angles to the placental edge. Small samples can be analysed and the localization of samples in relation to the placental edge and rupture site of the membranes can be standardized. The method is well suited for studies of premature rupture of fetal membranes. PMID- 2311813 TI - Duration of use of copper releasing IUDs and the incidence of copper wire breakage. AB - The incidence of copper wire breakage for IUDs (Multiloads) using 0.3 and 0.4 mm diameter copper wire was evaluated by examining 969 devices that had been removed for various reasons. The IUDs were examined by light microscopy to determine the integrity of the copper wire. As expected, the incidence of breakage increased with increasing duration of IUD use. The cumulative breakage rate (life table) was significantly lower (p less than 0.05) for the Multiload 375 that used 0.4 mm diameter wire, compared to the Multiload 250 that used 0.3 mm diameter wire. The cumulative rates were 5.4 per 100 IUDs after 3 years for the Multiload 250, and 3.8 per 100 IUDs after 5 years for the Multiload 375. In only 1 (0.1%) of the 969 Multiloads examined, the breakage of the copper wire was sufficiently extensive to adversely affect the user's risk of pregnancy. PMID- 2311814 TI - Virginal breast hypertrophy at puberty; a case report. AB - Plastic surgery reduction with free nipple graft was performed on an eleven and a half-year-old girl referred to us with massive bilateral macromastia. Hormonal studies revealed no abnormalities. Histopathological examination confirmed the diagnosis of virginal hypertrophy, an infrequent etiology in adolescent macromastia. PMID- 2311815 TI - Influence of parity on plasma lipid levels. AB - Plasma levels of total cholesterol (TC), HDL cholesterol (HDLC) and LDL cholesterol (LDLC), triacylglycerols (TG) and apoprotein (apo) A-I, A-II and B were measured in 516 women in the early puerperium. Different lipid plasma values (TC: 5.98 +/- 1.17 mmol/l, LDLC: 3.79 +/- 1.12 mmol/l, apo B: 108 +/- 24 mg/dl) and ratios (LDLC/HDLC: 2.85 +/- 1.09) were significantly (p less than 0.02) lower after the first pregnancy (n = 209) than after five or more pregnancies (n = 15) (TC: 6.50 +/- 2.10 mmol/l, LDLC: 4.36 +/- 1.97 mmol/l, apo B 130 +/- 50 mg/dl, LDLC/HDLC: 3.44 +/- 0.89). The opposite was true for the HDLC/TC ratio which was significantly lower (p less than 0.02) after five or more pregnancies (20.0 +/- 3.5) than after the first pregnancy (24.1 +/- 6.6). We also found a significant correlation (p less than 0.02) between the TC, LDLC, apo B and LDLC/HDLC ratio levels and parity. Other factors which could interfere with lipid metabolism (diet, body/mass index smoking, physical activity, alcohol intake) were not different between the various parity groups. Hence, we could not find a reason for the lipid elevation after the subsequent pregnancies. Although the higher lipid levels in puerperium of multipara should indicate a higher risk for progression of atherosclerosis, we need more studies before to conclude that multiparity influences the risk for coronary heart disease. PMID- 2311816 TI - C-reactive protein during normal pregnancy. AB - Serum C-reactive protein (CRP) is determined in a prospective longitudinal study of 60 low-risk pregnant women. CRP is also measured in umbilical-cord blood after delivery. The serum CRP concentrations seem to be independent of pregnancy and gestational age. The 95th percentile is estimated to be 20 mg/l, and this value is considered as the upper limit of normal. A rise in CRP level is considered more predictive of infection than a determination of a single high value. CRP does not cross the placental barrier, and may therefore be useful in diagnosing infections in newborns. PMID- 2311817 TI - An 'admission challenge test' to predict severe hypertension in pregnancy? AB - Although many pregnant women are admitted to hospital for 'high blood pressure' during the third trimester, less than a third of them will subsequently develop severe hypertension. We used a Dinamap 1846 vital signs monitor to measure the blood pressure every 5 min during the first hour in hospital of a group of 51 previously normotensive pregnant women admitted with hypertension. An average systolic pressure at or above 140 mmHg was recorded in 37% of patients and, of these, 68% went on to develop severe hypertension. Conversely, if the average systolic pressure on admission was below 140 mmHg, only 3% of patients later developed severe hypertension. In terms of sensitivity, specificity, and positive and negative predictive values of severe hypertension, the 1-hour automated blood pressure profile was superior to conventional measurements whether they were made prior to admission, on admission, or during the first 24 hours after admission. PMID- 2311818 TI - A computer model of antenatal care: relationship between the distribution of obstetric risk factors in simulated cases and in a real population. AB - The main purpose of antenatal care is to identify risk factors for the fetus. A number of systems have been described in which positive factors are summed to produce an overall risk score for the individual woman. In the present study a computer simulation of a population of pregnant women has been used to examine the use of Bayes theorem to calculate obstetric risk scores. The findings of the computer simulation have been compared with those in a real obstetric population (774 primigravidae; 930 multigravidae). A number of observations have been made which may be of considerable practical significance: (1) in the population as a whole the distribution of risk scores is skewed; most women have a low score while relatively few subjects have high scores; (2) a minimum number of risk factors must be present simultaneously for the risk in an individual to consistently exceed the overall population risk; this number is 4 in primigravidae and 5 in multigravidae; (3) the relationship between the number of risk factors and overall risk does not follow a straight line. The computer simulation provides a test bed in which various assumptions can be examined, such as the effect of removing or redefining given risk factors. PMID- 2311819 TI - Gardnerella vaginalis in posthysterectomy infection. AB - Eighty-six women were admitted for abdominal hysterectomy. Preoperatively, 43 women were culture-positive for Gardnerella vaginalis from the cervical os, and 43 women were culture-negative. Postoperatively, 18 patients developed inflammation; among those 14 patients from the culture-positive group were infected, whereas only 4 patients from the culture-negative group developed inflammation. The difference between occurrence of G. vaginalis and the absence of the bacteria in patients with postoperative infection is highly significant. No such increased risk of postoperative infection was correlated to the isolation of any other microorganism looked for viz. aerobic and anaerobic bacteria, yeasts, viruses or chlamydiae. G. vaginalis may play a causative role in the development of posthysterectomy infection. PMID- 2311820 TI - Anal sphincter function after delivery: a prospective study in women with sphincter rupture and controls. AB - Twenty-one consecutive women with anal sphincter muscle rupture during delivery (0.79%) and 15 controls were examined. The anal sphincter was immediately repaired in the study group and the function determined with anal profilometry at 3 days and 3 months after delivery, and in ten of the patients after 12 months. Anal sphincter strength was reduced soon after delivery in the controls but regained normal strength within 3 months. In the anal sphincter rupture group, an improvement was found over the first 3 months after delivery, but afterwards no further change occurred. The anal sphincter strength was significantly reduced compared to the control group, both soon after delivery and after 3 months. Their voluntary anal pressure increased from 1.7 kPa immediately after delivery to 3.2 kPa at 3 months in the study group and the corresponding values in the control group were 4.0 and 6.5 kPa, respectively. For the closing pressure, that is the resting pressure minus the rectal pressure, the values in the study group were 4.2 and 6.7 kPa, and in the control group 7.2 and 9.4 kPa, respectively. In the women with anal sphincter rupture, however, a significantly increased frequency of gas incontinence was found. PMID- 2311821 TI - Possible association between acetazolamide administration during pregnancy and metabolic disorders in the newborn. AB - Development of metabolic acidosis, hypocalcemia and hypomagnesemia in a preterm infant whose mother was treated with acetazolamide throughout pregnancy is described. These neonatal metabolic alterations possibly related to acetazolamide administration in pregnancy have not been previously described in the literature. The metabolic acidosis was transient and resolved spontaneously despite breast feeding and continued administration of acetazolamide to the mother. Hypocalcemia and hypomagnesemia resolved quickly with appropriate treatment with calcium gluconate and magnesium sulphate, respectively. At follow-up at ages 1, 3 and 8 months, the baby showed mild hypertonicity of the lower limbs requiring physiotherapy. PMID- 2311822 TI - Peptide mapping of intersubunit and receptor interactions of human choriogonadotropin. AB - Seven peptides covering the entire sequence of human choriogonadotropin (hCG) alpha-subunit, eight peptides covering the hCG beta-subunit sequence and two peptides, one of human beta-lutropin and one of beta-thyrotropin were synthesized. We checked their ability to prevent reassociation between hCG alpha- and beta-subunits and between hCG and its receptor. Only the alpha 1-22, alpha 59 92 and beta 1-16 peptides inhibited the reassociation between the alpha- and beta subunits of hCG with an ED50 of respectively 2 mM, 2 mM and 4 mM. Using porcine Leydig cells in primary culture, we showed that alpha 33-59, alpha 41-59 and beta 1-16 peptides decreased both the specific binding to the cell surface and the internalization of [125I]hCG and [125I]porcine LH with ED50 of 0.3, 0.1 and 0.5 mM, respectively. From these results, the following minimal area may be assigned, (i) to the alpha-beta interaction: alpha 5-16, alpha 52-72 (or alpha 59-70) and beta 8-16, and (ii) to the hormone-receptor association: alpha 41-45 and beta 8 16. PMID- 2311823 TI - Cloning and characterization of the rat alpha-inhibin gene. AB - The gene for the rat glycoprotein hormone alpha-inhibin has been cloned and characterized. The entire gene was found to be contained within a 5.5 kilobase EcoRI fragment. It is composed of two exons separated by a 1.5 kb intron. Primer extension and S1 nuclease analysis showed that the major transcription initiation site in the ovary was 77 bp from the start of translation. The promoter region of the gene did not contain a conventional TATA box but instead a number of GA rich repeated sequences were found to be present. Other potential regulatory elements found included a repeating purine-pyrimidine tract (TG)28, cAMP and phorbol ester response elements and a putative glucocorticoid response element. Southern blot analysis of rat genomic DNA indicated that there is a single gene for alpha inhibin in the rat. PMID- 2311824 TI - Detection of glycosylated growth hormone-binding proteins in rat serum. AB - Affinity cross-linking technique revealed the presence of three growth hormone binding proteins (GHBP) in dealbuminized rat serum. The apparent molecular weights, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were 52,000, 44,000 and 39,000. By use of carbohydrate chain cleaving enzymes it was found that the binding proteins contain N-linked complex carbohydrate chains, representing 8000, 4000 and 5000 in apparent molecular weight, respectively. Gel permeation chromatography and sucrose density gradient centrifugation revealed a growth hormone-binding entity with Stoke's radius 94.5 A (+/- 2.8, n = 5) and an s-value of 10.8 S (+/- 0.31, n = 5). The molecular weight could be calculated to 413,000. Both for gel chromatography and sucrose density gradient experiments unlabelled growth hormone reduced the radioactive peaks from 0 to 50%. The relation of this binding entity to the GHBP's described with affinity cross-linking technique and the nature of this binding entity is at present unclear. No serum binding protein(s) for prolactin was detected by affinity cross-linking technique, gel permeation chromatography or sucrose density gradient analysis. PMID- 2311825 TI - The 56 kDa androgen-binding protein in human genital skin fibroblasts: its relation to the human androgen receptor. AB - We have recently described in genital skin fibroblasts (GSF) a relatively abundant 56 kDa protein with androgen-binding activity. This protein is missing in GSF of most patients with complete androgen insensitivity syndrome (CAI). The protein has many characteristics compatible with the androgen receptor; it has in fact been tentatively considered as a precursor or degradation form of the prototypic (approximately 100 kDa) human androgen receptor. We have prepared an antiserum to this protein, which allowed us to detect it as a direct product by in vitro translation of mRNA from GSF. It is thus very unlikely to be a degradation product of a larger precursor. Furthermore, covalent photolytic labeling of this protein with the androgen analogue [3H]mibolerone revealed a much lower affinity for this protein than is known for the androgen receptor. Finally, the GSF of two exceptional patients with complete androgen insensitivity syndrome due to negligible androgen receptor-binding activity express this protein normally, as determined on two-dimensional gels by Western blot analysis with the antiserum and by photolytic covalent labeling with androgen analogues. These data indicate that the protein is not a precursor or a degradation product of the receptor; nor is it androgen-induced. They are more compatible with the idea that the protein is another member of the steroid/thyroid/retinoic acid receptor supergene family, perhaps as an unorthodox product of the human androgen receptor gene. PMID- 2311826 TI - Ultrasound demonstration of tongue motions during suckle feeding. AB - In this study the authors used ultrasound to demonstrate characteristic internal actions of the tongue during suckling. Its medial portion, into which the genioglossus is inserted, moves in relation to its lateral portions, into which the styloglossus and hyoglossus are inserted. A peristaltic wave of successive inferior and superior displacements moves posteriorly in the medial portion, compressing or 'milking' the nipple and propelling the expressed milk towards the pharynx. The lateral portions of the tongue enclose the nipple and the bolus and serve as reference for the displacements of the medial portion. These observations are related to anatomical studies of the tongue. The coordination pattern of suckle is compared with that of pharyngeal swallow. In instances where suckle and swallow are immediately sequential, the peristalsis which is common to both is continuous in the oral and pharyngeal portions of the food pathway. PMID- 2311827 TI - Late effects of central nervous system treatment of acute lymphoblastic leukemia in childhood are sex-dependent. AB - The authors measured the cognitive function and physical growth of 51 children who had been treated for acute lymphoblastic leukemia with chemotherapy, cranial irradiation and intrathecal methotrexate, and who had remained disease-free for five to 12 years. A comparison group of 15 children treated for Wilms' tumor was also studied. Cognitive impairment and growth retardation were greater among the leukemia group. Of potentially greater significance, however, was the finding that female sex was the pre-eminent risk factor for central nervous system toxicity resulting from treatment. Cognitive impairment, short stature and excessive weight were all more prevalent among females than males. Approximately half the children were microcephalic, but there was no sex difference. Age at evaluation and diagnosis, as well as socio-economic status, were differentially related to outcomes for the two sexes. The authors believe the sex differences were indicative of a fundamental interaction between postnatal neural development and other biological processes. PMID- 2311828 TI - Copying ability of preschool children with delayed language development. AB - Ninety-six 2 1/2-year-old children with delayed language development (identified by health visitors) and 100 controls were required to copy four simple items of the Griffiths Mental Development Scales, and were tested on the comprehension and expressive language scales of the Reynell Developmental Language Scales. The index children performed worse than the controls on all four copying tasks, and poor copying performance was related to both impaired language comprehension and expression. Copying by the index children was also poorer than their performance on two other non-verbal tasks. The implications for the assessment of children with delayed language development are considered, as well as theoretical implications with regard to the cognition/language debate. PMID- 2311829 TI - The syndromes described by Kanner and Rett-Hagberg: overlap in an extended family. AB - An extended family is reported in which Rett-Hagberg syndrome, autism with mild ataxia and autism with profound mental retardation occurred separately in three female second-cousins. The authors suggest alternative explanations for the possible association between autism and Rett-Hagberg syndrome: that they may be closely related genetic disorders, or that they may constitute relatively homogeneous phenotypes with several possible aetiologies. PMID- 2311831 TI - Callosal section for epilepsy and the avoidance of doing everything possible. PMID- 2311832 TI - Appointing directors: a new approach. PMID- 2311830 TI - Hidden intelligence of a multiply handicapped child with Joubert syndrome. AB - A child with Joubert syndrome (episodic hyperpnoea, abnormal eye-movements and ataxia) was followed from birth to eight years of age. Although severe mental retardation was suspected until approximately five years of age, unexpected and exceptional mental capacities were evident at later follow-up. Adequate testing and appropriate stimulation of children with such a severe early motor disorder are difficult, so they may give a false impression of mental retardation. The history of this child challenges the notion that mental retardation is part of Joubert syndrome. PMID- 2311833 TI - Measuring effectiveness in the physiotherapy department. PMID- 2311834 TI - A hospitalwide QA indicator report. PMID- 2311835 TI - Admission waiting times: a national survey. PMID- 2311836 TI - Cooperative planning in Newfoundland. PMID- 2311838 TI - CHA's new CEO. Interview by Henrik Andersen. PMID- 2311839 TI - Leave it to the experts. PMID- 2311837 TI - A hospitalwide discharge planning program. PMID- 2311840 TI - [Uncommon complication of sclerotherapy of esophageal varices: obstructive hematoma of the esophagus]. PMID- 2311841 TI - [A rare complication of sclerotherapy of esophageal varices: intramural pharyngoesophageal hematoma]. PMID- 2311842 TI - [Proctitis following the prolonged use of dextropropoxyphene and paracetamol suppositories: the risk persists despite change of excipient]. PMID- 2311843 TI - [Necrotico-hemorrhagic rectitis after lavage with hydrogen peroxide for fecaloma]. PMID- 2311844 TI - Elevated levels of soluble interleukin-2 receptors in Crohn's disease. PMID- 2311845 TI - [Exercise-induced heatstroke and hepatic involvement. Diagnostic and physiopathologic problems]. PMID- 2311846 TI - [A case of acute hepatitis caused by flutamide]. PMID- 2311847 TI - [Preoperative irradiation of rectal cancer improves local control and long term survival]. PMID- 2311848 TI - [Endoscopic detection of dysplasia and subclinical cancer of the esophagus. Results of a prospective study using toluidine blue vital staining in 100 patients with alcoholism and smoking]. AB - In spite of the development of upper digestive tract fiberoptic endoscopy (FE) within the last 10 years, early detection of esophageal carcinoma (EC) is rare except in certain high-risk groups such as patients with head and neck cancers. The aim of this study was to assess the value of a meticulous histoendoscopic examination with vital toluidine blue (TB) staining in all alcohol and tobacco abusers undergoing FE for any reason except dysphagia. In 18 months, 100 patients (90 men, 10 women) who were over 40 years old and who consumed more than 80 g of alcohol and 20 g of tobacco per day underwent FE. No patient had a history of head and neck or esophageal cancer. FE was decided in 48 patients for epigastric pain, in 28 for esophageal varices, in 8 for weight loss, in 8 for anemia, in 7 for peptic disease, and in 1 for diarrhea. Staining with TB was carried out at the end of the examination and two routine biopsies were obtained 5 cm above the lower esophageal sphincter. Specimens were obtained from each abnormal area (TB + or TB -). Clinical ENT examination was recommended for all patients. Two esophageal carcinomas (1 microinvasive, 1 in situ) and 15 cases of dysplasia were detected. Dysplasia was classified as severe in 1 case, moderate in 9 cases, and mild in 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311850 TI - [Experience of problems caused by biofeedback among the hospital staff]. PMID- 2311849 TI - [Mononuclear cell activation in Crohn's disease. Evaluation using serum assay of neopterin and interleukin-2 soluble receptors]. AB - To determine the degree of mononuclear blood cell activation in Crohn's disease (CD), 65 patients were prospectively investigated (22 with mild, 26 with moderate and 17 with severe disease). Serum levels of soluble receptors for interleukin-2 (SR-IL-2) were measured by ELISA. In CD patients SR-IL-2 levels were significantly higher (m = 707 +/- 326 U/ml) than in three other groups: 70 controls (m = 258 +/- 87 U/ml, p less than 0.0001); 8 patients with acute infectious colitis (m = 405 +/- 216 U/ml, p less than 0.0001); 101 HIV seropositive subjects (m = 564 +/- 216 U/ml, p less than 0.002). There was a positive correlation between SR-IL-2 level and the Van Hees activity index (r = 0.595, p less than 0.0001). On the other hand, the numbers of activated T cells (CD 3+, HLA DR+), CD 4+, CD 8+ and NK cells did not differ according to the CD activity groups. Furthermore, CD patients treated with steroids (n = 39) did not differ from those without any medication. As a marker of monocyte activation, serum neopterin level was determined by RIA. All CD patients considered as a group, serum neopterin level was 2.89 +/- 1.44 ng/l (n less than 2.5 ng/l). Neopterin level increased with disease activity (1.97 +/- 0.92 vs 3.10 +/- 1.46 vs 3.74 +/- 1.36, p less than 0.01), and was positively correlated with SR-IL-2 (r = 0.609, p less than 0.0001). These results suggest a monocyte-macrophage activation in CD, which parallels disease activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2311851 TI - [Prevention of post-transfusion hepatitis in Guadeloupe: results after application of new measures for detecting blood donors potentially at risk]. AB - One of the main concerns of blood transfusion centers is viral hepatitis as a direct result of blood transfusion. Ninety-five percent of these cases are non-A, non-B hepatitis. In order to prevent this disease, blood collections were screened for antibody anti-HBc as well as the level of activity of the alanine aminotransferase in 3,051 blood donors in Guadeloupe. this revealed a particular epidemiological situation, which caused this French country to be rated among moderate endemic zones for hepatitis B virus. As a result of this new screening procedure, 25 percent of the blood collected had to be discarded and was classified with prevalence rates of 21.8 percent HBc antibody, 2.9 percent HBs antigen, and 2.6 percent alanine aminotransferase (45 IU/l). Differences were noted according to sex, age, social-economical level and geographical origin of the blood donors. These data raised many significant questions regarding the vertical transmission of hepatitis B virus, the epidemiological situation of hepatitis B virus in the Guadeloupe population as well as in the rest of the French West-Indies, and also the type of action which must be taken against non A, non-B hepatitis in a moderate endemic zone for HBV. PMID- 2311852 TI - [Carcinoma in situ in localized Caroli's disease]. AB - A new case of Caroli's disease associated with cholangiocarcinoma is reported. It is the first in situ carcinoma description. Intrahepatic biliary cysts are a predisposing condition, even if mechanism remains hypothetical. PMID- 2311853 TI - [Prognosis and cirrhosis: attention to the risks]. PMID- 2311854 TI - [Digitalis poisoning with severe ischemic colitis: a favorable course after treatment with specific antibodies]. PMID- 2311855 TI - [Sclerosing peritonitis complicated by ischemic intestinal necrosis. X-ray computed tomographic aspects]. PMID- 2311856 TI - [Digestive mastocytosis, allergy to diesel oil and collagen colitis: a rare association?]. PMID- 2311857 TI - [Pseudocyst complicating acute pancreatitis. Ultrasonographic study]. PMID- 2311858 TI - Follow-up 6 to 11 years after duodenoscopic sphincterotomy for stones in patients with prior cholecystectomy. AB - One hundred sixty-three postcholecystectomy patients with retained or recurrent duct stones under-went successful duodenoscopic sphincterotomy and duct clearance between 1975 and 1980. Follow-up information was obtained on 148 patients in 1982, and on 115 of these in 1986 (at a mean of 8 yr). Fifteen patients (13%) were found to have had further biliary problems, but only 5 were known to have had sphincter stenosis and/or stones, and only 3 had not responded to endoscopic or conservative treatment. One had undergone choledochoduodenostomy for recurrent cholangitis (but continued to have problems), and 1 had died with jaundice, the precise cause of which was unknown. The third continued to have episodes of cholangitis requiring antibiotics despite the apparent lack of biliary obstruction. Bile showed significant bacterial contamination in 60% of 44 patients undergoing check endoscopy, but there was no correlation with symptoms. These long-term results are comparable with those of surgical procedures and justify the continuing use of endoscopic treatment for patients with duct stones. PMID- 2311859 TI - Quantitation of the hepatic arterial buffer response to graded changes in portal blood flow. AB - Hepatic arterial blood flow changes inversely in response to altered portal blood flow. The hepatic arterial capacity to buffer portal flow changes was studied over a wide range of portal flow with arterial pressure held steady (the active buffer response) or uncontrolled. The active component of the buffer response led to nearly full dilation of the hepatic artery at low portal flows as shown by inability to dilate further in response to adenosine infusion; at high portal flows the hepatic artery was nearly fully constricted as shown by lack of further constriction to norepinephrine. With pressure uncontrolled, active and passive effects combined to produce an increased compensation with similar efficiency (44% +/- 4%) over the full range of portal blood flows. Thus, although the active component of the hepatic arterial buffer response becomes less efficient at very high and low portal flows, the combination of active and passive effects leads to a larger buffer capacity which is equally efficient over a wide range of portal blood flow changes. PMID- 2311860 TI - Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea. AB - Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5 microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients. PMID- 2311861 TI - X antigen/antibody markers in hepadnavirus infections. Presence and significance of hepadnavirus X gene product(s) in serum. AB - The finding that X antigen is associated with hepatitis B core antigen particles and that serum hepatitis B e antigen derives from the cleavage of one or more core associated polypeptides raises the question as to whether core associated X antigen could be similarly generated and released into serum. To test this hypothesis, antisera raised to X antigen peptides were used to construct an enzyme-linked solid-phase immunoassay to detect X antigen in sera from patients infected with hepatitis B virus and from woodchucks infected with woodchuck hepatitis virus. X antigen was present in more than half of the individuals tested. There was a significant association between X antigen and markers of viral replication. Most individuals destined to become surface-antigen carriers had X antigen appearing before surface antigen, as did a smaller proportion of individuals transiently positive for surface antigen. A high frequency of X antigen was observed only in sera from human populations with a high frequency of other hepatitis B virus markers. These results suggest that X is a newly identified serum marker of viral replication that often appears before surface antigen in productive infections. PMID- 2311862 TI - Improvement in chronic hepatocerebral degeneration following liver transplantation. AB - Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation. PMID- 2311863 TI - Reports from the NIH DDDN. Human liver tissue for research. PMID- 2311864 TI - Biliary stricture: is dilatation an acceptable alternative to operation? PMID- 2311865 TI - Is oriental folk use of bear bile vindicated (yet)? PMID- 2311866 TI - Protein kinase C unleashed. PMID- 2311867 TI - Internal anal sphincter in patients with fecal incontinence. PMID- 2311868 TI - The gastroenterologist and microvascular angina. PMID- 2311869 TI - Ileocolonoscopy in patients with spondylarthritis and/or asymmetric oligoarthritis. PMID- 2311870 TI - Early recurrence of primary biliary cirrhosis after liver transplantation. PMID- 2311871 TI - Flow cytometry and dysplasia in Barrett's esophagus. PMID- 2311872 TI - Legionella infection in ulcerative colitis. PMID- 2311873 TI - Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. AB - Intragastric capsaicin protects against ethanol-induced gross mucosal lesion formation by stimulation of afferent nerve endings in the rat stomach. The aims of the present study were to examine histologically the protective effect of capsaicin and to test whether this effect is related to changes in mucosal eicosanoid formation and mucosal blood flow. Intragastric capsaicin (160 microM) significantly reduced gross mucosal lesion formation induced by 25% ethanol. Light microscopy revealed that the depth of erosions was attenuated likewise. However, capsaicin did not prevent ethanol from causing superficial damage to the mucosa as observed by light and scanning electron microscopy. The protective action of capsaicin against ethanol remained unchanged by a dose of indomethacin that reduced the ex vivo formation of prostaglandin E2 and 6-oxo-prostaglandin F1 alpha in the gastric mucosa by about 90%. Capsaicin alone did not affect the ex vivo formation of these prostaglandins and of leukotriene C4. Intragastric capsaicin (160 microM) enhanced gastric mucosal blood flow by 89% as measured by the hydrogen gas clearance technique. This effect was also observed when capsaicin was administered together with 25% ethanol. These data indicate that afferent nerve stimulation by intragastric capsaicin protects against deep mucosal damage in response to ethanol, an effect that seems related to an increase in mucosal blood flow but not to eicosanoid formation. PMID- 2311874 TI - Human duodenal mucosal bicarbonate secretion. Evidence suggesting active transport under basal and stimulated conditions. AB - When the proximal duodenum of animals or humans is perfused with isoosmolar NaCl, bicarbonate enters the luminal effluent. In addition, duodenal bicarbonate output is stimulated by luminal acidification and prostaglandins of the E class. The hypothesis that in vivo human duodenal bicarbonate transport persists in the absence of a plasma-to-lumen bicarbonate gradient and therefore is probably an active transport process was tested. In healthy subjects, a 4-cm segment of the proximal duodenum was isolated from gastric and pancreaticobillary secretions. Net duodenal bicarbonate secretion remained similar to basal levels during luminal perfusion with either 24 or 32 mM bicarbonate (each isoosmolar with plasma by the addition of NaCl). In addition, peak increases in acid-induced bicarbonate outputs with luminal perfusion of 154 mM NaCl and 32 mM NaHCO3 (+122 mM NaCl) were similar. Moreover, prostaglandin E2-stimulated bicarbonate secretion with perfusion of 154 mM NaCl and 32 mM NaHCO3 (+122 mM NaCl) was similar. It was concluded that in humans, proximal duodenal mucosal bicarbonate transport remains unaltered in the absence of a plasma-to-lumen bicarbonate gradient at rest and after stimulation with HCl or prostaglandin E2. These observations suggest that human proximal duodenal bicarbonate secretion involves active transport. PMID- 2311875 TI - Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xanthine oxidase-derived radicals. AB - Ethanol-induced gastric mucosal injury closely resembles an inflammatory response. Thus, in vivo and in vitro experimental models were used to assess whether ethanol is proinflammatory in concentrations likely to be encountered by the gastric mucosa during acute intoxication. Perfusing the rat gastric lumen with progressively increasing concentrations of ethanol (10%, 20%, and 30%) resulted in a dose-dependent increase in 51Cr-ethylenediaminetetraacetic acid clearance from blood-to-gastric lumen. Rendering the animals neutropenic (with antineutrophil serum) ameliorated the ethanol-induced mucosal injury; the degree of protection was directly related to the severity of neutropenia. Neither superoxide dismutase, catalase, nor sodium benzoate offered any protection against ethanol-induced injury, indicating that neither superoxide anion, hydrogen peroxide, nor the hydroxyl radical is involved. To assess further whether ethanol could exert proinflammatory effects an in vitro model consisting of cultured bovine microvascular endothelial cells and isolated human neutrophils was used. Ethanol at concentrations of 1.0%-4.0% (but not at 0.1%-0.5%) increased neutrophil adherence to endothelial cells and enhanced neutrophil-mediated endothelial cell injury. We conclude that ethanol is proinflammatory at concentrations that may be achieved in the gastric mucosa during acute intoxication. The ethanol-induced, neutrophil-mediated cell injury does not appear to involve oxy radicals. PMID- 2311876 TI - Histamine metabolism in human gastric mucosa. Effect of pentagastrin stimulation. AB - The metabolism of histamine in the human gastric mucosa was studied in the basal state and during pentagastrin stimulation. Studies were made in healthy volunteers and in patients with peptic ulcer disease. Mucosal biopsies were taken from antral and oxyntic gland areas whereupon histamine content, histidine decarboxylase activity, and histamine methyltransferase activity were simultaneously assayed. Histamine content of the oxyntic gland mucosa was decreased as a consequence of pentagastrin administration in all groups studied, and this decrease was numerically largest in patients with duodenal ulcer disease. Pentagastrin induced a significant increase in histidine decarboxylase activity of the oxyntic gland mucosa with the most profound increase seen in patients with duodenal ulcer. The highest rates of histamine formation were present in the oxyntic mucosa of patients with Zollinger-Ellison syndrome. The activity of histamine methyltransferase was the same in all groups studied and was not changed by pentagastrin. In conclusion, pentagastrin administration in humans is followed by a significant mobilization of histamine only from the oxyntic gland mucosa, an effect that is more pronounced in patients with duodenal ulcer disease. PMID- 2311877 TI - Increased epidermal growth factor receptors in gastric carcinomas. AB - The epidermal growth factor and the homologous alpha-tumor growth factor are mitogenic polypeptides that act by binding to the epidermal growth factor receptor. The present study investigated whether increased production of epidermal growth factor/alpha-tumor growth factor or increased density of epidermal growth factor receptors may occur in gastric carcinomas as compared with normal mucosa from the same individuals. Epidermal growth factor receptors were measurable by (125I)EGF-binding assays in 13 of 15 normal mucosas and in 15 of 15 carcinomas. The epidermal growth factor-binding capacity was significantly higher in carcinomas than in mucosa. A comparison of pairs of mucosa and carcinomas showed an increase of epidermal growth factor receptors in 9 of 15 carcinomas, no change in 3, and a decrease in 2 carcinomas. One mucinous adenocarcinoma contained extreme numbers of epidermal growth factor receptors (2445 fmol/mg protein) corresponding to a 320-fold increase over normal mucosa. Epidermal growth factor-like activity was increased in 2 of 22 carcinomas compared with mucosa. We conclude that relative overexpression of epidermal growth factor receptors occurs in a fraction of gastric carcinomas. Whether increased expression of epidermal growth factor receptors is associated with particular patterns of tumor progression needs to be investigated. PMID- 2311878 TI - Effect of age and sensitivity to cholecystokinin on gallstone formation in the guinea pig. AB - The purpose of this study was to evaluate the effect of age and the role of cholecystokinin therapy on gallstone formation in guinea pigs. Guinea pigs (31 1 mo-old, 31 1-yr-old, and 23 3-yr-old) were placed on a cholelithogenic diet for 2 wk while another 10 guinea pigs of each age group remained on regular chow. Half of each group received a daily injection of cholecystokinin (0.5 nmol/kg). After 2 wk, guinea pigs were killed and the gallbladders were examined for gallstones. The concentrations of bile constituents were determined. The prevalence of gallstones was: 1-mo-old, control 0 out of 16, cholecystokinin 1 out of 15; 1-yr old, control 3 out of 14, cholecystokinin 5 out of 16; 3-yr-old, control 10 out of 11, cholecystokinin 3 out of 8. Gallstone formation was significantly greater in 3-yr-old controls than in the two younger control groups, and cholecystokinin treatment significantly reduced the incidence of gallstones to near the level seen in younger guinea pigs. In the two younger age groups (but not in the 3-yr old group), the cholelithogenic diet significantly reduced the concentration of bile salts in bile below that of guinea pigs on a normal diet. The cholelithogenic diet and treatment with cholecystokinin did not alter the relative compositions of bile lipids from that of guinea pigs on a normal diet in any of the three ages studied. In the second experiment we measured gallbladder emptying in response to exogenous infusion of cholecystokinin-8 (100 fmol/kg/h 100 nmol/kg/h) in the same three age groups of guinea pigs in vivo that had been maintained on regular chow. There was no difference in cholecystokinin sensitivity between the two younger age groups, but both were significantly more sensitive to cholecystokinin than the 3-yr-old guinea pigs in rate of gallbladder emptying in the dose range 1 pmol/kg/h-1 nmol/kg/h. We conclude that a major factor in the increased incidence of gallstone formation in the aged guinea pig gallstone model is decreased gallbladder emptying due to decreased gallbladder sensitivity to cholecystokinin. PMID- 2311879 TI - Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis. AB - Endoscopic and biopsy findings of the esophagus, stomach, duodenum, and colorectum were studied in 37 patients with amyloidosis involving the gastrointestinal tract. Endoscopic examinations revealed fine granular appearance, polypoid protrusions, erosions, ulcerations, and mucosal friability in many cases. These findings were most marked and noticed most often in the second portion of the duodenum. The frequency of amyloid deposition in the biopsy specimens was as follows; 100% in the duodenum, 95% in the stomach, 91% in the colorectum, and 72% in the esophagus. The degree of amyloid deposition in the duodenum, which was the highest of the entire gastrointestinal tract, significantly correlated with the frequency of endoscopic findings such as fine granular appearance and polypoid protrusions. Therefore, the two endoscopic findings described above are characteristic of this disease and may reflect amyloid deposition in the mucosa or submucosa of the alimentary tract. Our results indicate that for a diagnosis of amyloidosis, it is important to examine the upper gastrointestinal tract, especially the duodenum, using endoscopy and biopsy techniques. PMID- 2311880 TI - Physiologic changes during colonoscopy. AB - We prospectively evaluated multiple physiologic parameters in 104 consecutive unselected patients undergoing elective colonoscopy. Changes observed during colonoscopy were then correlated with the type of anesthesia and level of sedation, position of the endoscope and presence of looping, existence of comorbid medical conditions, concomitant medication usage, and the occurrence of endoscopy induced pain. Clinically important changes in O2 saturation (54%) and in blood pressure (44%) were most frequently noted. Less frequent were changes in pulse (15%) or respiratory rate (4%). These clinically significant changes were associated with induction of anesthesia or endoscope looping and pain in 58 to 62% of the patients. In the remainder of patients, no obvious factor was associated with the observed alterations in physiologic parameters. There was no correlation with presence of comorbid medical conditions, use of concurrent medication, dose of anesthesia, level of sedation, and/or colon segment reached by the endoscope. Although there was no apparent morbidity associated with the induced changes in physiologic parameters, these data suggest that certain patients may be at increased risk of procedure-related morbidity and support the need for physiologic monitoring in high-risk patients. PMID- 2311881 TI - Nasal oxygen alleviates hypoxemia in colonoscopy patients sedated with midazolam and meperidine. AB - A randomized study was carried out to determine whether the administration of oxygen (3 liter/min) via nasal prongs significantly affects arterial oxygenation during colonoscopy in patients sedated with intravenous midazolam (2.6 +/- 0.2 mg, means +/- SE) and meperidine (48 +/- 3 mg). Patients who received supplemental oxygen were less likely to become hypoxic (pulse oximeter reading, SpO2 less than 90%) than those who breathed room air (10 of 28 vs. 22 of 28, p less than 0.005). Similarly, the total time during which SpO2 was below 90% was significantly less in patients receiving nasal oxygen (0.7 +/- 0.3 min) than in patients breathing room air (9.7 +/- 1.9 min, p less than 0.001). Minimum oxygen saturations were significantly higher in patients receiving oxygen (90.6 +/- 0.8%) than in patients breathing air (86.5 +/- 0.8%, p less than 0.001). In patients breathing air, there was a significant negative correlation between the dose of meperidine and the minimum observed oxygen saturation; conversely, midazolam dose did not correlate with indices of hypoxemia. The authors conclude that administration of oxygen via nasal prongs can reduce the risk of hypoxemia during colonoscopy. However, since hypoxemia may occur even when nasal oxygen is given, continuous monitoring of arterial oxygenation is recommended. PMID- 2311882 TI - Study of the gastric mucosal background in patients with gastric polyps. AB - The characteristics of gastric mucosal patterns in the polyp-bearing stomach were investigated by the endoscopic Congo red test and systemic four-points biopsy in 46 patients with hyperplastic polyps and 21 patients with gastric adenomas. In addition, function of the stomach in these patients was assessed by determination of gastric acidity and fasting serum gastrin level and by gastrin response test to a beef extract. In the investigation of the gastric mucosal pattern in hyperplastic polyp patients, Type A gastritis (involving the corpus but sparing the antrum) was most frequently found. On the other hand, extensive intestinal metaplasia from the pyloric antrum to the corpus was most often noted in the adenoma-bearing stomach. Hypergastrinemia was more marked in hyperplastic polyp patients, and may be involved in the pathogenesis of hyperplastic polyps. Attention should be paid to the detection of cancer in areas without polyps during endoscopic observation and reexamination of patients. On these occasions, the characteristics of the background mucosa for each type of polyp should be kept in mind. PMID- 2311883 TI - Teaching gastrointestinal endoscopy by computer simulation: a prototype for colonoscopy and ERCP. PMID- 2311884 TI - The bifid pancreas: a rare anatomical variation. PMID- 2311885 TI - Recurrent pancreatitis in a young patient associated with a solitary nonopaque concretion in the main pancreatic duct. PMID- 2311886 TI - Squamous cell metaplasia without dysplasia of the colonic mucosa in ulcerative colitis. PMID- 2311888 TI - Colonoscopy with fluoroscopy. PMID- 2311887 TI - Endoscopic esophageal intubation for treatment of chronic esophago-cutaneous fistula. PMID- 2311889 TI - Colonoscopy without fluoroscopy. PMID- 2311890 TI - Privileges to perform endoscopy. PMID- 2311891 TI - Air, air, everywhere: pneumatosis cystoides coli after colonoscopy. PMID- 2311892 TI - Variceal ulceration following sclerotherapy: normal consequence or complication? PMID- 2311893 TI - Through the nose with the gastroscope. PMID- 2311894 TI - Upper esophageal sphincter spasm as a marker of monilial esophagitis. PMID- 2311895 TI - Fibrin glue: is it practical in the treatment of acute upper gastrointestinal bleed? PMID- 2311896 TI - A technique for preventing iatrogenic bleeding during sclerotherapy. PMID- 2311897 TI - Post-traumatic pancreatitis. PMID- 2311898 TI - Resourceful management of esophageal food impaction. PMID- 2311899 TI - Retroperitoneal lymphoma causing pancreatic ductal obstruction on endoscopic retrograde cholangiopancreatography. PMID- 2311900 TI - Biopsy proven rectal endometriosis demonstrating early decidual reaction. PMID- 2311901 TI - The design and production of videotapes for endoscopic teaching. PMID- 2311903 TI - [Fertility following tubal pregnancy: comparison of tube-saving surgery and salpingectomy]. AB - 391 patients were operated during 1980 to 1987 at the Department of Gynaecology of the University of Tubingen for extrauterine pregnancy. A questionnaire was circulated to inquire, how many of these women wanted to become pregnant again. 176 answered positively, the return quota being 82%. After surgery, performed to preserve the Fallopian tubes, 64% of these patients had an intrauterine pregnancy, compared with only 41% after salpingectomy or segmental resection without anastomosis. In women without the characteristic factors which reduce fertility, such as primary sterility, surgery concerning sterility or refertilization, or other kinds of abdominal surgery, a greater proportion of intrauterine pregnancies was seen after surgery preserving the Fallopian tubes (79%), than in women with the above mentioned risk factors (53%). The incidence of repeat extrauterine pregnancies was approximately equal after Fallopian tube preserving surgery and after salpingectomy (20% and 18%, respectively). PMID- 2311902 TI - [AIDS and females. Change in problems for the gynecologist]. AB - We report on our experience with 47 HIV-positive women, died in the meantime. 32% stated, that they had never taken i.v. drugs. Their clinical pattern varies greatly. Psychosocial problems and infections, such as genital herpes and candidosis and others predominate. Long-term controls of 12 couples with HIV negative male partner only showed one case of HIV-transmission. Since 1980 21 children were born by these patients, 7 of them are seropositive 2 years after birth, and one of them has meanwhile died of AIDS. PMID- 2311904 TI - [Complications of intravenous therapy with peripheral indwelling catheter]. AB - Intravenous fluid replacement via a peripheral catheter harbours several risks. The study presented emphasizes that about 50% of the patients show complications during the first days after positioning of an intravenous line. Women patients have been affected more often than male patients. Small catheters positioned in a major vessel away from a joint in the forearm, yield the best results. Peripheral lines should be removed within 8 to 12 hours after surgical procedures, when early symptoms are observed. Complications can be avoided by following these recommendations. PMID- 2311905 TI - [Results of a physician survey on the status of knowledge and attitude to natural family planning in West Germany 1988]. AB - Based on a questionnaire, reporters of the EMNID Poll Institute interviewed 229 general practitioners and 237 practising gynaecologists by telephone. When questioned which method for family planning was, in the physicians' opinion, most frequently used and which was most frequently recommended by physicians, contraceptive pills were far ahead of any other method. Somewhat surprising was the fact that up to 36% of the interviewed physicians considered that the intrauterine device is either the most frequently used or the most recommended method. Even the quantity of reports on condoms being the most frequently used method was relatively high (8-10%). 6% of the questioned physicians stated NFP methods as being mainly used, and 10% of the physicians recommended these methods. NFP methods also held the fourth place preceded by contraceptive pills, IUD and condom in the 1985 EMNID survey. Among the NFP methods, body basal temperature was reported to be the most popular and most frequently recommended method. The sympto-thermal method which is world-wide proposed as first choice by the experts, is still fairly unknown. The results arising from this survey indicate the necessity for physicians to gain a more thorough knowledge of modern NFP methods. Unjustified prejudices should be removed, the high reliability, which may be achieved at present, should be propagated and the undeniable advantages of NFP methods should be pointed out. The possible difficulties due to the necessary abstinence during the fertile period should, however, be kept in mind. PMID- 2311906 TI - [Coping behavior and supplying medical information--a study of mothers having delivered a child with a lip-jaw-palate cleft]. AB - To be delivered of a child with cleft lip and palate is an extreme psychic stress factor for the mother. In coping with this, she is left to the support of the caring medical staff. Therefore, the aim of the present study was 1. to ascertain, to what extent mothers of children with cleft lip and palate are given information on the malformation, and receive emotional support by the medical staff; and 2. to determine the effect such experiences have on their ability to cope. For this purpose we developed a special questionnaire, which was completed by 154 mothers of such children. Retrospectively, a relevant part of them criticised not only the communication and the contents of information, but also the emotional support as deficient. A correlation between these determinants and largely insufficient coping was statistically confirmed. Our results should be taken into account in respect of the practical requirements when caring for mothers of children with a cleft lip and palate. PMID- 2311907 TI - [Osteoporosis and pre- and postpartal heparin therapy]. AB - Multiple vertebral compression fractures occurred in the 33rd week of pregnancy in a breast-feeding mother receiving heparin (20,000-25,000 units/die over 5 months), for deep vein thrombosis. Osteoporosis under heparin therapy is a rare complication and this diagnosis was not made despite obvious clinical signs. It follows from this observation, that heparin therapy should be substituted by oral anticoagulant therapy and discontinued directly after delivery. PMID- 2311908 TI - [Diagnosis and therapy of hyperthyroidism in pregnancy]. AB - In pregnancy hyperthyroidism occurs with a prevalence of 0.04-0.2%. It occurs even less frequently de novo in previously undiagnosed patients. Within a short period of time we treated 3 patients, who also developed signs of pre-eclampsia. Specific principles of the management during pregnancy are explained. PMID- 2311909 TI - [The organization of perinatal centers]. PMID- 2311910 TI - [Pathologic Papanicolaou--class IV smear without histologic correlate--what should be done?]. PMID- 2311911 TI - A practical method for the analysis of osmotic-and-diffusive energy conversion. AB - A practical method for the study of osmotic- and-diffusive conversion of free energy of solutions with different concentrations is presented. Equations for effective power, dissipative power, total power and energetic efficiency have been derived for fixed membrane systems. These equations allow energetic evaluation of these systems. The significance of the method for biological studies is also suggested. PMID- 2311912 TI - Thallium and rubidium permeability of human and rat erythrocyte membrane. AB - Transport of Tl+ and Rb+ in human and rat erythrocytes was investigated in the presence of ouabain. The chloride-dependent cotransport of Tl+, Rb+ and Na+ was precluded by replacement of Cl- by NO3-. The inward and outward rate constants for the residual fluxes of the cations were determined by measuring the transport of 204Tl and 86Rb in double label experiments. The rate of passive transport of Tl+ exceeded that of Rb+ by one-two orders of magnitude in human as well as rat erythrocytes. The membrane barrier which contributes to the maintenance of ion gradients was shown not to be a barrier for Tl+ which easily penetrates the membrane by an unknown mechanism. In rat erythrocytes the barrier for Rb+ was 10 15 times weaker than that in human red blood cells, while the corresponding ratio of rat/human Tl+ permeabilities was about 1.8-2.0. It follows that Tl+ permeability is only slightly affected by factors modifying the permeability to alkali cations. The increase of temperature from 20 degrees to 37 degrees C resulted in a three-fourfold stimulation of the passive transport of Tl+ both in human and rat erythrocytes. The movement of Tl+ and Rb+ through the erythrocyte membrane differed substantially from their diffusion along the excitable membrane channels characterized both by poor Tl+/K+ selectivity and weak temperature dependence. PMID- 2311913 TI - Effect of oxidized phospholipids on the chemiluminescence of zymosan-activated leukocytes. AB - The effect of liposomes with different degree of oxidation on the zymosan-induced chemiluminescence (CL) of leukocytes was investigated. Non-oxidized liposomes did not influence significantly the CL response of leukocytes. In contrast previously oxidized liposomes increased CL even if liposomes and cells were separated by a dialysis membrane. Based on the observed increase of luminol-activated CL by oxidized liposomes, lipid peroxidation (LPO) products may be suggested to enhance cell activation. Zymosan-activated leukocytes did not affect the amount of malondialdehyde (MDA) in non-oxidized liposomes unless iron salts were added. Fe3+ + ADP added to non-oxidized liposomes triggered LPO. Both catalase and superoxide dismutase (SOD) prevented the effect. In experiments with previously oxidized liposomes the activated oxygen species produced by leukocytes did not increase the amount of MDA; on the contrary, they decreased it both in the presence and in the absence of chelated iron in the liposome suspension. The reaction between lipid hydroperoxide and O2- widely accompanied by CL. SOD decreased CL in this system by a factor of 1.7. On the other hand, peroxidized lipids may "opsonize" initially inactive particles: oxidized liposomes increased CL response of leukocytes similarly as opsonized zymosan routinely used as a phagocyte activator. PMID- 2311914 TI - The effect of neomycin on contractile activity of the canine cervical lymphatic vessel induced by various agents. AB - The effects of neomycin on isometric contractions induced by norepinephrine (NE), alpha 1-adrenoceptor agonist phenylephrine (PE), KCl, and an activator of GTP binding proteins (G-proteins) NaF were studied in the isolated canine cervical lymphatic vessel (CLV). Incubation of the CLV with 0.3 or 1.3 mmol/l neomycin for 30-180 min did not affect significantly either the basal vascular tone or the response to NE, and potentiated the response to KCl by 24 +/- 6% (p less than 0.05). On the other hand, neomycin (1.3 mmol/l) treatment reduced by 22 +/- 6% (p less than 0.05) the contractions induced by PE and completely (by 96 +/- 3%, p less than 0.001) suppressed the effects of NaF. Upon the combined action of NaF and NE, neomycin reduced only NaF-component of the total response. Verapamil (100 mumol/l) had no effect on the magnitude of NaF-induced tension and partially inhibited NE- and PE-induced contractions (by 20 +/- 4% (p less than 0.05) and 53 +/- 5% (p less than 0.01), respectively). Indomethacin (10 mumol/l) did not influence significantly the contractions evoked by NE, KCl, and NaF either under control conditions or in the presence of neomycin. These data suggest that the phosphoinositides may considerably contribute to the CLV contractions evoked by NaF, but do not play a substantial role in the responses of the vessel to alpha adrenergic stimulation and KCl. PMID- 2311915 TI - Comparison of the effects of dDAVP and AVP on the sodium transport in the frog skin. AB - The effect of 1-deamino-8-D-arginine-vasopressin, dDAVP, the synthetic analogue of vasopressin, upon the active sodium transport across the frog skin was studied using standard microelectrode technique and compared with the effect of synthetic arginine-vasopressin, AVP. dDAVP applied to the basolateral side of the epithelium stimulated the active sodium transport as reflected by the increase of short-circuit current, Isc, and transepithelial electrical potential difference, Voc. Potential difference across both the apical, Vo, and the basolateral, Vi, cell membranes decreased. The driving force of transepithelial sodium transport, ENa, did not change. The transepithelial electrical resistance, Rt, ohmic resistance of the active sodium transport, RNa, and apical cell membrane resistance, Ro, rapidly decreased, while the resistance of the basolateral cell membrane, Ri, and the resistance of the shunt pathway, Rs, remained unchanged. It is concluded that dDAVP primarily increases sodium permeability of the apical cell membrane which subsequently stimulates sodium pump activity. This action is similar to that of AVP. PMID- 2311916 TI - Isolation of omnipotent suppressors in an [eta+] yeast strain. AB - Omnipotent suppressors decrease translational fidelity and cause misreading of nonsense codons. In the presence of the non-Mendelian factor [eta+], some alleles of previously isolated omnipotent suppressors are lethal. Thus the current search was conducted in an [eta+] strain in an effort to identify new suppressor loci. A new omnipotent suppressor, SUP39, and alleles of sup35, sup45, SUP44 and SUP46 were identified. Efficiencies of the dominant suppressors were dramatically reduced in strains that were cured of non-Mendelian factors by growth on guanidine hydrochloride. Wild-type alleles of SUP44 and SUP46 were cloned and these clones were used to facilitate the genetic analyses. SUP44 was shown to be on chromosome VII linked to cyh2, and SUP46 was clearly identified as distinct from the linked sup45. PMID- 2311917 TI - How does the cell count the number of ectopic copies of a gene in the premeiotic inactivation process acting in Ascobolus immersus? AB - Repeated genes, artificially introduced in Ascobolus immersus by integrative transformation, are frequently inactivated during the sexual phase. Inactivation is observed in about 50% of meioses if duplicated genes are at ectopic chromosomal locations, and in 90% of meioses if genes are tandemly repeated. Inactivation is associated with extensive methylation of the cytosine residues of the duplicated sequences and is induced in the still haploid nuclei of the dikaryotic cell which will undergo karyogamy and subsequent meiosis. Only repeated sequences become methylated. This raises the intriguing question of how the premeiotic inactivation machinery is informed that a nucleus contains multiple copies of a gene. By using in crosses recombinant strains of A. immersus in which either one, two or three genetically independent copies of the exogenous amdS gene from Aspergillus nidulans had been introduced, we could follow the premeiotic inactivation of each one of the ectopic amdS copies. This led us to propose that a prerequisite for inactivation is a premeiotic pairing of repeated sequences and that each copy can undergo successive cycles of pairing. In fact, once methylated, a copy can pair with a still unmethylated copy, so that an uneven number of copies can be subject to inactivation. PMID- 2311918 TI - Pairing for recombination in LGV of Caenorhabditis elegans: a model based on recombination in deficiency heterozygotes. AB - The effect of deficiencies on recombination was studied in Caenorhabditis elegans. Heterozygous deficiencies in the left half of linkage group V [LGV(left)] were shown to inhibit recombination to their right. Fourteen deficiencies, all to the left of unc-46, were analyzed for their effect on recombination along LGV. The deficiencies fell into two groups: 10 "major inhibitors" which reduce recombination to less than 11% of the expected rate between themselves and unc-46; and four "minor inhibitors" which reduce recombination, but to a much lesser extent. All four minor inhibitors delete the left-most known gene on the chromosome, while six of the ten major inhibitors do not (i.e., these are "internal" deficiencies). Where recombination could be measured on both sides of a deficiency, recombination was inhibited to the right but not to the left. In order to explain these results we have erected a model for the manner in which pairing for recombination takes place. In doing so, we identify a new region of LGV, near the left terminus, that is important for the pairing process. PMID- 2311919 TI - Interrelationships of heterozygosity, growth rate and heterozygote deficiencies in the coot clam, Mulinia lateralis. AB - Allozyme surveys of marine invertebrates commonly report heterozygote deficiencies, a correlation between multiple locus heterozygosity and size, or both. Hypotheses advanced to account for these phenomena include inbreeding, null alleles, selection, spatial or temporal Wahlund effects, aneuploidy and molecular imprinting. Previous studies have been unable to clearly distinguish among these alternative hypotheses. This report analyzes a large data set (1906 individuals, 15 allozyme loci) from a single field collection of the coot clam Mulinia lateralis and demonstrates (1) significant heterozygote deficiencies at 13 of 15 loci, (2) a correlation between the magnitude of heterozygote deficiency at a locus and the effect of heterozygosity at that locus on shell length, and (3) a distribution of multilocus heterozygosity which deviates from that predicted by observed single-locus heterozygosities. A critical examination of the abovementioned hypotheses as sources of these findings rules out inbreeding, null alleles, aneuploidy, population mixing and imprinting as sole causes. The pooling of larval subpopulations subjected to varying degrees of selection, aneuploidy or imprinting could account for the patterns observed in this study. PMID- 2311920 TI - Spatial autocorrelation of genotypes under directional selection. AB - The spatial distributions of genetic variation under selection-mutation equilibrium within populations that have limited dispersal are investigated. The results show that directional selection with moderate strength rapidly reduces the amount of genetic structure and spatial autocorrelations far below that predicted for selectively neutral loci. For the latter, homozygotes are spatially clustered into separate areas or patches, each consisting of several hundred homozygotes. When selection is added the patches of the deleterious homozygotes are much smaller, in the range of 25 to 50 individuals. Selection also reduces temporal correlations. Also investigated are the effects of random replacement processes, such as mutation, immigration, and long-distance migration, on spatial and temporal correlations. The detection of natural selection through spatial pattern analysis is discussed, and applied to data from populations of the morning glory, Ipomoea purpurea. PMID- 2311921 TI - Pleiotropic models of quantitative variation. AB - It is widely held that each gene typically affects many characters, and that each character is affected by many genes. Moreover, strong stabilizing selection cannot act on an indefinitely large number of independent traits. This makes it likely that heritable variation in any one trait is maintained as a side effect of polymorphisms which have nothing to do with selection on that trait. This paper examines the idea that variation is maintained as the pleiotropic side effect of either deleterious mutation, or balancing selection. If mutation is responsible, it must produce alleles which are only mildly deleterious (s approximately 10(-3)), but nevertheless have significant effects on the trait. Balancing selection can readily maintain high heritabilities; however, selection must be spread over many weakly selected polymorphisms if large responses to artificial selection are to be possible. In both classes of pleiotropic model, extreme phenotypes are less fit, giving the appearance of stabilizing selection on the trait. However, it is shown that this effect is weak (of the same order as the selection on each gene): the strong stabilizing selection which is often observed is likely to be caused by correlations with a limited number of directly selected traits. Possible experiments for distinguishing the alternatives are discussed. PMID- 2311922 TI - DNA fingerprints applied to gene introgression in breeding programs. AB - An application of DNA fingerprints (DFP) for gene introgression in breeding programs of both farm animals and plants is proposed. DFP loci, detectable by minisatellite probes, are extremely polymorphic. Individuals have unique patterns of DFP and thus can be selected for maximal genomic similarity to the recipient line, and minimal similarity to the donor line, using their DFP patterns as the criterion for similarity. This genomic selection (GS) can be performed at generations BC1, BC2 or both, and thus significantly reduce the required number of backcross generations in introgression breeding programs. The association between genomic and DFP similarity is demonstrated. Theoretical distributions and variances of the relative percentages of the donor and recipient genomes as the basis for the GS approach are presented. PMID- 2311923 TI - Foods as occupational allergens: Part I. An international conference. September 8 9, 1988, Washington, DC. Proceedings. PMID- 2311925 TI - Immunologic skin diseases. (2nd Eastern Allergy Conference). PMID- 2311924 TI - Classic reactions to foods (by ingestion). PMID- 2311926 TI - Photosensitivity disease: pathophysiology and management. AB - The clinical manifestations, pathophysiology, and treatment of the following common photosensitivity diseases are reviewed in this article: polymorphous light eruption, solar urticaria, drug-induced photodermatoses, chronic actinic dermatitis, porphyria cutanea tarda, and erythropoietic protoporphyria. PMID- 2311928 TI - Warning: eat, do not inhale. PMID- 2311927 TI - Prevalence of allergy to Hymenoptera stings. AB - In this study, we evaluated the prevalence of systemic reactions to hymenoptera stings in an adult general population, 20-60 years old. The protocol included a standardized questionnaire, skin tests to venom in subjects reporting a history of systemic reaction, and in subjects reporting a history of severe local and systemic reactions, as well as in a control group, a radioallergosorbent test (RAST) to hymenoptera venoms. According to the questionnaire, 1.2% of the study population had a history of systemic reactions. Only 0.85% had both such a history and a positive skin test to venoms. RASTs were positive, for at least one venom, in 57% of subjects with a history of systemic reaction, 15.8% of subjects with a history of severe local reactions, and 6.0% of the control group. In conclusion, this study shows that systemic reactions are not uncommon in the general population. RASTs tests are not sensitive or specific enough to be considered, per se, for indications of allergy to venoms. PMID- 2311929 TI - The basic immunology of allergic diseases. PMID- 2311930 TI - Classical food allergens. PMID- 2311931 TI - Structure of the gene encoding beta-1,3-glucanase A1 of Bacillus circulans WL-12. AB - The nucleotide sequence of the glcA gene encoding the precursor of extracellular beta-1,3-glucanase (beta Gl) A1, a polysaccharidase produced by Bacillus circulans WL-12, was determined. The putative glcA gene was 2046 bp long, encoding a polypeptide of 682 amino acids (aa). The N-terminal aa sequence of beta Gl produced in Escherichia coli harboring the glcA plasmid was identical to that of beta Gl A1 prepared from the culture fluid of B. circulans WL-12. In both proteins, cleavage of the signal sequence of pre-beta Gl occurred between Ala-38 and Ala-39 of the predicted sequences. PMID- 2311932 TI - Cloning of a second xylanase-encoding gene of Streptomyces lividans 66. AB - A second xylanase-encoding gene (xln) of Streptomyces lividans 66 was cloned by functional complementation of a xylanase/endocellulase-negative double mutant of S. lividans, using the multicopy plasmid pIJ702. Three clones contained a common 3.1-kb DNA fragment encoding the biosynthesis of a 31-kDa xylanase and a 22-kDa protein which was immunorelated. The xylanase represented at least 80% of the total secreted proteins. These three clones also secreted a small amount of the previously reported 43-kDa xylanase which was detected only by using specific antibodies. Most likely, the DNA fragment contained the complete structural xln gene and some regulatory sequences, since the enzymatic activity was repressed by glucose. In the in vitro transcription-translation system, the plasmid pIAF42 encoded an immunoprecipitable 35-kDa xylanase indicating the presence of a 4-kDa signal peptide. PMID- 2311933 TI - Cloning and characterization of the gene encoding a blasticidin S acetyltransferase from Streptoverticillum sp. AB - A gene (bls) encoding a blasticidin S-acetyltransferase from Streptoverticillum sp. JCM4673 was cloned in the Streptomyces plasmid pIJ702 and expressed in S. lividans 1326. Four of the recombinant plasmids contained a common 1129-bp BclI PstI DNA fragment, which by subcloning experiments was shown to carry the bls gene. Sequencing of the 1129-bp BclI-PstI fragment indicated that it contains two open reading frames of 408 and 366 nucleotides (nt), both starting with ATG and terminating at TGA triplets. Deletion analysis showed that the correct bls sequence is that of 408 nt, whose deduced amino acid sequence conforms to a polypeptide of Mr 15073. A 175-bp DNA fragment from the 5' region of the bls gene had promoter activity in the promoter-probe plasmid pIJ486. PMID- 2311934 TI - Mutational analysis of the phage T4 morphogenetic 31 gene, whose product interacts with the Escherichia coli GroEL protein. AB - The phage T4 morphogenetic gene 31 has been sequenced. Its deduced gene product is a polypeptide of 111 aa, with a predicted Mr of 12064 and a pI of 4.88. The proof that the assigned open reading frame (ORF) encodes Gp31 rests on the sequencing of two known gene 31 amber mutations, amN54 and NG71, demonstrating that these mutations result in translational termination within the assigned ORF. Furthermore, the sequencing of four different T4 epsilon mutations, isolated on the basis of allowing the phage to propagate on Escherichia coli groEL- hosts, showed that they are either missense mutations or 3-bp deletions in the gene 31 reading frame. The sequencing of neighboring DNA revealed the presence of five other ORFs, one of which overlaps gene 31 substantially, but in the opposite orientation. PMID- 2311935 TI - A regulatory gene, angR, of the iron uptake system of Vibrio anguillarum: similarity with phage P22 cro and regulation by iron. AB - The angR locus in Vibrio anguillarum encodes a trans-acting transcriptional activator which modulates several Fe2(+)-regulated loci in the anguibactin biosynthesis gene cluster. In this paper, the complete nucleotide (nt) sequence of the angR gene and deduced amino acid (aa) sequence of the AngR protein are presented. A region upstream from the angR gene is shown to have similarity with Fe2(+)-regulated operators in Escherichia coli which bind the Fur protein. The involvement of a Fur-like regulator is supported by transcription analysis which show that angR itself is Fe2(+)-regulated. The aa sequence of the AngR protein predicts a helix-turn-helix motif which shows striking homology with prokaryotic DNA-binding proteins, particularly the lambda and P22 Cro proteins. In addition, there are two 18-nt regions, upstream from the angR gene, which show similarity with the OR1 and OR2 operators of P22 cro. These regions overlap with, respectively, the -35, -10 region and the putative Fur-binding region upstream from angR. These results suggest that AngR may be a DNA-binding protein which modulates Fe2(+)-regulated transcription and is itself Fe2(+)-regulated at the transcriptional level. PMID- 2311936 TI - Cloning and expression of genes involved in 4-chlorobiphenyl transformation by Pseudomonas testosteroni: homology to polychlorobiphenyl-degrading genes in other bacteria. AB - The genes of Pseudomonas testosteroni strain B-356, specifying the transformation of 4-chlorobiphenyl (4-CB) into 4-chlorobenzoic acid (4-CBA) were cloned into Pseudomonas putida KT2440 using a broad-host-range cosmid, pPSA842. Of 10,000 clones tested, four were able to transform 4-CB. Gas chromatographic and mass spectrometric analysis of the catabolic products from two of the 4-CB transforming clones carrying the hybrid plasmids, pDA1 and pDA2, demonstrated that pDA1 carried a complete set of structural genes involved in the transformation of 4-CB into 4-CBA, while pDA2 contained part of the pathway genes leading up to the meta-cleavage compound. Restriction endonuclease mapping and subcloning of pDA1 and pDA2 showed that the clones contained a common stretch of DNA of about 9.1 kb and that pDA2 carried gene(s) involved in regulation. Probing blots of genomic DNA from 13 different polychlorinated biphenyl(PCB)-degrading bacteria with radio-labelled pDA1 and pDA2, suggested that many PCB-degrading pathways have a common phylogenetic origin. PMID- 2311937 TI - Modular organization of the lytic enzymes of Streptococcus pneumoniae and its bacteriophages. AB - The nucleotide sequences of genes cpl7 and cpl9 of the Streptococcus pneumoniae bacteriophages Cp-7 and Cp-9, encoding the muramidases CPL-7 and CPL-9, respectively, have been determined. The N-terminal domains of CPL-7 and CPL-9 were virtually identical to that previously reported for the CPL-1 muramidase. The C-terminal domain of the CPL-7 muramidase, however, was different from those of the host amidase and the phage Cp-1 and Cp-9 lysozymes. Whereas all enzymes studied are characterized by repeated sequences at their C termini, the repeat unit lengths are 20 amino acids (aa) in CPL-1, CPL-9 and in the host amidase, but 48 aa in CPL-7. Six repeated sequences represent the C-terminal domains of CPL-1, CPL-9 and the host amidase, and 2.8 perfect tandem repetitions that of CPL-7. The peculiar characteristics of the structure of CPL-7 muramidase correlate with its biochemical and biological properties. Whereas CPL-1, CPL-9 and the pneumococcal amidase strictly depend on the presence of choline-containing cell walls for activity, CPL-7 is able to degrade cell walls containing either choline or ethanolamine. These results support the previously postulated role for the C terminal domain of these lytic enzymes in substrate recognition and provide further experimental evidence supporting the notion that the proteins have evolved by an exchange of modular units. PMID- 2311938 TI - Isolation of bioluminescent functions from Photobacterium leiognathi: analysis of luxA, luxB, luxG and neighboring genes. AB - Genes encoding luminescence of Photobacterium leiognathi have been cloned in Escherichia coli. The luminescent clones were readily apparent. Among them, a clone containing a recombinant plasmid with a 13.5-kb insertion was identified. This DNA fragment contained all of the luminescence-encoding genes. The luciferase-encoding genes (lux) in this DNA fragment were localized. We have sequenced a part of the cloned lux region and identified the luxA, luxB and luxG genes encoding the alpha and beta subunits of luciferase and a gamma protein with an Mr of 26,180, respectively. The analysis of deduced amino acid sequences and comparison with known luciferase sequences from Vibrio harveyi, indicate the common origin of these proteins. PMID- 2311939 TI - Cutaneous eruption with or without ocular complications in patients with herpes zoster involving the trigeminal nerve. AB - We examined 62 patients with acute herpes zoster involving the trigeminal nerve; 13 had eruptions only and 49 (51 eyes) had eruptions with ocular complications. Bilateral involvement was found in two patients. The frequency of the disease appeared to increase with age, and the disease was least active in November. Patients with eruptions only demonstrated affected areas along the first, second, and/or third divisions of the trigeminal nerve. Ocular complications occurred in patients who had eruptions along the first and/or second divisions of the nerve, and they were usually noted in patients with eruptions on the tip and one side of the node. The ocular complications and associated systemic conditions varied. PMID- 2311940 TI - Intravitreal silicone oil injection: complications and treatment of 415 consecutive patients. AB - Silicone oil injection in conjunction with pars plana vitrectomy was carried out by five surgeons in 415 consecutive patients using the same surgical equipment, the same surgical techniques and the same highly purified silicone oil (viscosity, 5000 mPa.s). Indications for silicone oil injection after vitrectomy included advanced stages of proliferative vitreoretinopathy following rhegmatogenous retinal detachment (49%), severe proliferative diabetic retinopathy (38%), and proliferative vitreoretinopathy following retinal detachment due to ocular trauma (13%). Postoperative complications were noted in a 6- to 30-month follow-up period. Cataractous changes of varying degree were seen in all phakic eyes. Silicone oil entered the anterior chamber in 6% of all phakic and pseudophakic eyes. Subretinal silicone oil was noted in 4%. Other complications associated with the use of intravitreal silicone oil included biomicroscopically visible silicone oil emulsification (0.7%), keratopathy (5.5%), glaucoma (6%), closure of the inferior iridectomy (6%), and reproliferation of epiretinal and subretinal fibrous membranes (40%). We anticipate that the physico-chemical characteristics of the highly purified silicone oil (viscosity, 5000 mPa.s) and the routine performance of an inferior iridectomy in all aphakic eyes had a positive impact on the low incidence of silicone-oil-related complications such as emulsification, keratopathy and secondary glaucoma. PMID- 2311941 TI - A comparison of three clinical methods of spatial contrast-sensitivity testing in normal subjects. AB - Three methods clinically used for measuring spatial contrast sensitivity were performed monocularly in normal subjects to compare their sensitivity and applicability. The methods tested were (1) the Von Bekesy tracking procedure, (2) the Method of Increasing Contrast, both carried out on a Nicolet CS-2000 automated Vision Tester, and (3) the Vistech Contrast Test System, a photographic test chart. The results show that the threshold sensitivities of the Von Bekesy tracking procedure and the Method of Increasing Contrast were not significantly different. For sensitivity to middle and high spatial frequency, the Vistech test chart was found to approximate the Method of Increasing Contrast. With automated testing, a slower rate of contrast progression and a larger visual angle produced lower thresholds of detection of the contrast-sensitivity function. Using a slow rate of contrast progression, both the Vistech test chart and the Method of Increasing Contrast were rapidly conducted, easy to administer, and gave good approximations of the spatial contrast-sensitivity function. PMID- 2311942 TI - The posterior coats of the eye in glaucoma. An echobiometric study. AB - The axial length of the eye and the thickness of the posterior coats of the eye were measured sonographically in 50 eyes of 25 patients with glaucoma. From these data, the volume of the posterior half of the ocular coats was calculated. The intraocular pressure (IOP) of the patients varied between 10 and 69 mmHg. A negative correlation was found between the IOP and the ocular coat dimensions (thickness and volume, r = 0.5, P less than 0.05 and r = 0.6, P less than 0.005, respectively). The possible connection between elevated IOP and the choroidal circulation is also discussed. PMID- 2311943 TI - Diffuse necrotizing retinochoroiditis in a child with AIDS and toxoplasmic encephalitis. AB - We examined a child with a human immunodeficiency virus (HIV) infection who at 15 months of age developed acute encephalitis, followed 1 week later by a diffuse, uniocular retinochoroiditis. The clinical picture in the right eye was characterized by the occurrence of some intraretinal hemorrhages; punctate, yellow-white, outer retinal lesions temporal to the macula; and a quadrantal, white area of necrotic retina located superotemporally. - The vitreous was remarkably clear, and the left eye was normal. Fluorescein angiography revealed small spots of late hyperfluorescence, vasculitis in the posterior pole, and a persistently hypofluorescent quadrantal superotemporal area. Toxoplasma IgM antibodies that were absent 1 week after birth became detectable in the serum and the cerebrospinal fluid. Serological testing for cytomegalovirus was negative. Neurological signs improved on a specific therapy (pyrimethamine and sulfamethopirazine), but the patient died 2 months later of disseminated cytomegalovirus infection. PMID- 2311944 TI - Intraocular penetration of rifampin after oral administration. AB - Rifampin, the most potent anti-staphylococcal drug known, was examined for its penetration into the aqueous and vitreous of rabbits after a single oral dose of 150 mg, 300 mg, or 600 mg. Maximum levels after the 150 mg dose were achieved at 4 h and were 4.2 micrograms/ml in the aqueous and 2.2 micrograms/ml in the vitreous. After the 300 mg dose, maximum levels were also achieved at 4 h, and were 5.0 micrograms/ml in the aqueous and 2.6 micrograms/ml in the vitreous. The 600 mg dose produced maximum levels at 6 h after administration, with 20.0 micrograms/ml in the aqueous and 15.2 micrograms/ml in the vitreous. These levels exceed the minimum inhibitory concentration for many microorganisms and suggest additional investigation into possible applications of systemic rifampin in the prophylaxis and treatment of bacterial endophthalmitis. PMID- 2311945 TI - Ciliary neuromuscular morphology in cynomolgus monkeys after ciliary ganglionectomy. AB - Cynomolgus monkeys underwent unilateral ciliary ganglionectomy (CG) and/or posterior ciliary neurectomy (PCN). The ciliary muscle was functionally denervated, as evidenced by loss of choline acetyltransferase activity, loss of the accommodative response to topical eserine and electrical stimulation of the Edinger-Westphal nucleus, and supersensitivity of the accommodative response to pilocarpine. Light and electron microscopy carried out 3-28 days after CG/PCN revealed degeneration of myelinated and unmyelinated nerve fibers as evidenced by axonal swelling and shrinkage, mitochondrial degeneration, axoplasmic condensation and vacuolization, and activated, phagocytosing Schwann cells. By 1 3 months after CG/PCN, few non-myelinated axons remained between the muscle bundles, larger nerve bundles were disordered and deteriorated, and Schwann cells filled with lipid and cellular debris were prominent. Beyond 6 months (6-37 months), most eyes were reinnervated by functional criteria. Concurrently, the ciliary neuromuscular morphology appeared virtually normal, exhibiting many non myelinated axons containing numerous agranular synaptic vesicles and large mitochondria; however, remnants of degenerated axons were still present. In two eyes remaining functionally denervated, many of the unmyelinated axons between the ciliary muscle bundles were swollen or empty, with small, degenerated mitochondria and only rare synaptic vesicles, and were often ensheathed by thickened, condensed Schwann-cell cytoplasm. The muscle fibers were atrophic and separated from each other as well as from the ensheathed nerve fibers. Thus, following CG/PCN, the morphologic and functional evidence of parasympathetic denervation and reinnervation of the ciliary muscle is pathophysiologically and temporally consistent. PMID- 2311946 TI - Posterior vitreous detachment following panretinal laser photocoagulation. AB - A total of 30 eyes of 19 patients with type I diabetes, varying severity of retinopathy, and no posterior vitreous detachment (PVD) were studied clinically, and vitreous examination was performed by preset lens biomicroscopy. Follow-up was 4.0-7.5 years. A total of 15 eyes underwent panretinal laser photocoagulation (PRP) and 15 eyes were left untreated. The incidence of PVD was 8 of 15 353%) after PRP and 1 of 15 (7%) in untreated eyes (P less than 0.02). Minimal vitreous hemorrhage occurred in 4 of 7 treated eyes (57%) that did not develop PVD and in only 2 of 8 (25%) that did. In treated eyes with no history of vitreous hemorrhage, the incidence of PVD was 6/9 (67%); in treated eyes with minimal vitreous hemorrhage at any time, it was 2/6 (33%). In treated eyes, the presence of Diabetic Retinopathy Study (DRS) high-risk characteristics was equally frequent in eyes that developed PVD as in those that did not. These data suggest that PVD occurs following PRP, independent of the severity of diabetic retinopathy or prior vitreous hemorrhage. PMID- 2311947 TI - Experimental autologous inverse keratoplasty--epithelial, stromal and endothelial interactions. AB - After the reversal of a 4-mm central corneal button in 20 rabbits, no epithelial proliferation was observed in the anterior chamber. The epithelium and the wound margins facing the anterior chamber were covered by a large fibrin clot, which suppressed epithelial cell growth and served as a matrix for rapidly proliferating fibroblasts while apparently stimulating their growth. The inverted epithelium was overgrown by stromal tissue and eventually disappeared. Fibrous proliferation ceased after tissue had been covered by corneal endothelium. We suggest that fibrin clotting and stromal fibroblastic proliferation are important factors that prevent epithelial growth on the inner corneal surface. PMID- 2311948 TI - Effective methods for the investigation of human tear film proteins and lipids. AB - The investigation of human tear film proteins and lipids is of value for the elucidation of contact lens incompatibilities, tear film instabilities, dry eye syndrome and various other eye diseases. Improved efficient methods for the investigation of human tear film proteins and lipids are presented in this paper. Tear proteins were examined by ultrathin sodium dodecyl sulfate-polyacrylamide gel electrophoresis, celluloacetate gel, isoelectric focusing, and high performance liquid chromatography. The methods differ in sensitivity, resolution, convenience and reproducibility. Tear lipids were examined by high-performance thin-layer chromatography, and good separation into the major lipid classes was achieved. With this method it is possible to examine the lipids present in tears of an individual subject and not just in pools made up from the tears of several persons. PMID- 2311949 TI - Experimental studies on the angiogenic activity of the detached retina. AB - Angiogenic activity of the retina in experimentally induced retinal detachment in cats was examined using the corneal micropocket technique and chorioallantoic membrane assay. The results of these studies indicate that the detached retina possesses higher angiogenic activity than the normal, attached retina. This suggests that disturbances in the nourishment by the choroid of outer retinal layers may play a role in the pathogenesis of ocular neovascularization. PMID- 2311950 TI - Posterior axial corneal malformation and uveoretinal angiodysgenesis--a neurocristopathy? AB - This clinicopathological report describes an unusual combination of axial corneal malformation and angiodysgenesis in the uvea, retina and optic nerve in three eyes. In each specimen there was hypocellularity in the posterior axial stroma, with corresponding loss of the corneal endothelium. The vascular malformation consisted of numerous telangiectatic endothelium-lined tubes with inconspicuous or absent media. One globe was obtained from a stillborn fetus (36 weeks) in which renal agenesis and a sireniform malformation (mermaid fetus) occurred in conjunction with a Fallot's tetralogy, pulmonary hypoplasia and atresia of the trachea and duodenum. Eyes with almost identical malformations were obtained from a 39-week female neonate who died after 5 h as a consequence of renal agenesis and pulmonary hypoplasia. This combination of ocular tissue malformations can be explained by embryological studies, which have shown that the corneal stroma and endothelium and the ocular periendothelial vascular tissues are derived from the neural crest. PMID- 2311951 TI - Attitudes of elderly people about clinical research on aging. AB - This study determined the factors influencing participation of elderly people in research. It involved subjects who signed consent for a study and those who refused consent. Consenters had significantly more positive feelings about being used as a subject; giving urine; giving blood; having a physical examination; being interviewed; taking an IQ test; answering questions; being a subject to help others; finding out about problems and as a way to pass time; and telling an interviewer the truth. Reasons given for partaking in research were the personality of the interviewer, interest in the project, and benefits to subject or others. PMID- 2311952 TI - A descriptive analysis of nursing staff behaviors in a teaching nursing home: differences among NAs, LPNs, and RNs. AB - Various staff behaviors in a nursing home were sampled seven times a day, 5 days a week over 37 months and were coded separately for LPNs, RNs, and NAs. The behavior most frequently observed was patient care, which occurred during 56.9% of the samples. We observed staff interacting with patients during 10.7% and with other staff during 19.5% of the samples. The LPNs displayed significantly more patient care behaviors and NAs significantly more nonwork behaviors than other nursing staff. RNs displayed the least nonwork behavior. We conclude that nursing staff devote most of their time to patient needs and relatively little time to nonproductive activities. PMID- 2311953 TI - Sexual concerns of male spouses of female Alzheimer's disease patients. AB - Little is known about the impact of dementia on sexuality. The attendant cognitive changes that occur in the Alzheimer's patient present the caregiver with many, often conflicting, challenges to a couple's sexual functioning. This case study highlights these issues by describing a man who reported an erectile dysfunction directly stemming from stressful changes that had occurred in his relationship to his wife who had Alzheimer's disease. General themes and relevant hypotheses are derived and clinical practice implications are explored. PMID- 2311954 TI - Assessments of institutionalized dementia patients' competencies to participate in intimate relationships. AB - Although sexual interests in institutionalized elderly patients have long been recognized (Comfort, 1974; Wasow & Loeb, 1974), guidelines to help determine patients' competencies to participate in intimate relationships are not delineated in the literature. This paper describes the assessment technique used by an interdisciplinary staff on a coed Alzheimer's disease unit. Two case studies are presented to highlight how the assessment led to the treatment decisions. PMID- 2311955 TI - A model state-level approach to family survival for caregivers of brain-impaired adults. AB - This profile of a statewide program to support family caregivers of brain impaired adults identifies the major needs and problems of these family caregivers and delineates service interventions to meet those needs. Demographic data on the major characteristics of over 3,000 family caregivers and their cognitively impaired patients are reported. A discussion on addressing brain impairment as a broad category of disability needing an array of policies and programs regardless of individual diagnostic categories, is provided. PMID- 2311956 TI - A program for caregivers in the workplace. AB - In four demonstration sites, an educational seminar series was offered to employed caregivers, followed by a choice of service options (i.e., care planning, a support group, a buddy system). An increase in absenteeism and knowledge of aging services was associated with attendance at the seminar series. Among the service options, only care planning and support groups were utilized by employees. A decrease in negative affect was associated with each of the options. PMID- 2311957 TI - Case for biomedical priorities in dementia research. PMID- 2311958 TI - Nursing home length of stay patterns: results from the 1985 National Nursing Home Survey. AB - Length of stay (LOS) for elderly nursing home patients is estimated by converting discharges from the 1985 National Nursing Home Survey into an admission cohort and by adding reported immediate previous nursing home LOS to the surveyed LOS. The ultimate length of aggregated stays is longer than unaggregated estimates for elderly discharged residents. Although the mean length of aggregated stays is 19 months, the mean unaggregated stay is only 13 months. PMID- 2311959 TI - Social networks and health: impact on returning home after entry into residential care homes. AB - This research extends the study of social network analysis and labeling theories into the context of residential care homes (RCHs). Findings suggest that: (1) when members of intense social networks decide to move elderly persons into RCHs, placement is truly needed and (2) although the likelihood of returning home from RCHs is affected by sociocultural characteristics, the functional and cognitive status of the resident are of primary importance. PMID- 2311961 TI - College students' expectations of grandparent and grandchild role behaviors. AB - Survey responses of 704 college students revealed that the majority of college students have at least one grandparent, and some have eight or more. Students identified degree of closeness with most close grandmother and grandfather. Students' perceptions of grandparent and grandchild roles were generally positive, indicating affection and respect for grandparents. This study is compared with Robertson's study of student attitudes from 12 years ago. Analyses of variance with gender, race, and family form as independent variables reveal differences on role attitudes among students from various backgrounds. PMID- 2311960 TI - The transition from caregiving to bereavement: the relationship of care-related strain and adjustment to death. AB - This study examines two competing hypotheses about the relationship between care related strain and the difficulty adjusting to the impaired relative's death. One hypothesis, and the limited available empirical evidence, suggests that family members who perceive caregiving as stressful will experience some relief when their relative dies because care responsibilities end. An alternative hypothesis, derived from several conceptualizations, posits the opposite relationship, with greater care-related strain predictive of greater strain during bereavement. Panel data from spouse and adult-child caregivers collected before and after the death support the second hypothesis. Respondents who appraise caregiving as more difficult and those who report more negative caregiving consequences for the family assess bereavement as more difficult and report greater bereavement strain for the family. PMID- 2311962 TI - Nursing home staff and residents' families role expectations. AB - This study evaluates role expectancies in essential nursing services of nursing home professionals and relatives of residents. Whereas previous studies have indicated substantial role ambiguity, the present research indicates significant agreement between the groups. Even so, areas exist where families deem themselves responsible for a task, but staff expectations are incongruent. Analysis of this process and steps to ameliorate this problem are discussed. PMID- 2311964 TI - Correlates of senior center participation: a national analysis. AB - This paper presents results of a logit regression analysis of the correlates of senior center participation for a national sample of 13,737 elders from the Supplement on Aging of the 1984 National Health Interview Survey. Significant characteristics were higher levels of social interaction, decreasing income, living alone, fewer ADL-IADL difficulties, being female, and living in suburbs and rural nonfarm areas. Curvilinear relationships between center use and age and education were found. Race, self-reported health status, and residence in urban and rural farm areas were nonsignificant when the other variables were controlled. PMID- 2311963 TI - An empirical study of proxy consent for elderly persons. AB - To investigate empirical assumptions about substituted judgment, three treatment decision scenarios were presented to 43 competent elderly persons and 115 persons related to them. Related subjects who were explicitly asked to make a substituted judgment came significantly closer to the elderly person's preferences than those who were asked to make their best recommendation (p = .005-.067, depending on index used). These results support the use of a substituted judgment approach to proxy decision makers; other results suggest some limitations of durable powers of attorney. PMID- 2311965 TI - The metropolitanization and suburbanization of the U.S. elderly population: 1970 1988. AB - This paper analyzes U.S. Census, Current Population Survey data from 1970 to 1988. It establishes that the young-old (age 65-74) and old-old (75 plus) populations are now more likely to live in metropolitan areas, especially within suburban areas, and are occupying residential locations that are less segregated from other age groups. As early as 1977 the majority of metropolitan elderly people lived in suburban areas, and by 1988 only just over one-quarter of the U.S. elderly population lived in nonmetropolitan areas. PMID- 2311966 TI - Language acculturation among older Vietnamese refugee adults. AB - The purpose of this study was to examine the English language acculturation among older Vietnamese refugees (aged 40 and over) in a nationwide sample. The findings reveal that age, sex, education in Vietnam, health, and length of residence in the U.S. had some significant relationships with language acculturation. In particular, older Vietnamese people had more problems with language acculturation than their younger counterparts, and Vietnamese women had more language acculturation problems than men. PMID- 2311967 TI - Endoscopic demands in the 90's. PMID- 2311968 TI - ECG record during changes in oesophageal pH. AB - Seventeen patients with non-cardiac chest pain were investigated by simultaneous ambulatory 24 hour ECG and oesophageal pH monitoring. While 11 patients lowered their oesophageal pH below 4 for a significant percentage, (3.4%) of recorded time and experienced chest pain, no simultaneous ECG changes occurred. In 10 patients chest pain was reproduced by an oesophageal acid perfusion test (Bernstein test). No changes in ECG record during the test were shown. We conclude that although reflux oesophageal pain may be difficult to differentiate from cardiac pain, clinically oesophageal pH changes do not produce any ECG changes. PMID- 2311969 TI - Value of the 24 hour intraoesophageal pH monitoring in children. AB - Twenty four hour oesophageal intraluminal pH probe studies were performed in 114 children (range age: one month-12 years) referred for symptoms or signs compatible with gastroesophageal reflux. Forty five patients had reflux disease alone, 69 had evidence of oesophagitis which was assessed endoscopically and histologically. Recordings were also performed in 63 control patients. The occurrence of reflux was analysed for the total study period and particularly while awake, asleep, fasting, and during postcibal periods. Oesophageal acid exposure time and the number of reflux episodes lasting greater than five minutes during the total study period provided the best discrimination between patients and controls; however, 20% and 30% of all reflux patients had both normal (with 2 SD of control) acid exposure time and number of long lasting reflux episodes, respectively. Patients with oesophagitis had significantly more acid reflux than those with simple uncomplicated disease during postcibal, fasting, awake periods, but not during sleep; however, increasing severity of oesophagitis was not associated with increasing acid exposure. The ability of the intraluminal oesophageal pH test to discriminate patients with various degrees of reflux disease decreased if only postprandial pH variables were taken into account. We conclude that: (1) the 24 hour intraoesophageal pH monitoring may present false negative results that limit overall sensitivity of the test; (2) the presence of oesophagitis does not seem to be associated with increased oesophageal acid exposure during sleep; (3) limiting the pH recording to postprandial periods reduces the discriminatory power of the test. PMID- 2311971 TI - Tightly spiral shaped bacteria in the human stomach: another cause of active chronic gastritis? AB - Tightly spiral shaped Gram negative bacteria were seen in the gastric biopsies obtained from two patients undergoing gastroscopy. Active chronic gastritis was present in both patients and one patient also had gastric ulceration. Attempts to culture the organism by a number of methods were unsuccessful but positive urease results were obtained in both patients. Both patients were treated with colloidal bismuth subcitrate. Biopsies taken after treatment showed resolution of infection and histological gastritis. These results suggest that Helicobacter pylori is not the only organism associated with chronic active gastritis in man. PMID- 2311970 TI - Bacterial adhesion and disease activity in Helicobacter associated chronic gastritis. AB - Ultrastructural examination of biopsies showing Helicobacter pylori associated chronic gastritis reveals close attachment between gastric surface epithelial cells and the organism. The finding of 'adhesion pedestals', which represents a cellular response to the presence of the organism, is analogous to the response of intestinal cells to enteropathogenic E coli. Thus the development of bacterial attachment sites in H pylori associated gastritis might be an indication of pathogenicity. We have therefore explored the relationship between the proportion of organisms forming attachment sites and histological indices of disease 'activity'. Antral biopsies from 40 patients with H pylori positive gastritis were examined histologically and ultrastructurally, and the percentage of attached organisms compared with subjective assessments of epithelial degeneration, mucin depletion, polymorphonuclear and chronic inflammatory cell infiltration. We found a significant increase in the proportion of attached bacteria in cases showing histological epithelial degeneration, and a significant decrease in cases showing intraepithelial polymorph infiltration. The direct relationship between bacterial attachment and cellular degeneration lends further support to a pathogenic effect. Reduced attachment in the face of polymorph infiltration might indirectly reflect aspects of the immune response--namely, blocking of adhesion by IgA, with complement activation and generation of leucotactic factors. PMID- 2311972 TI - Gastric enterochromaffin-like (ECL) cells in hypergastrinaemic duodenal ulcer disease. AB - Patients with hypergastrinaemic duodenal ulcer disease were studied to determine whether chronic moderate hypergastrinaemia produces hyperplasia of gastric enterochromaffin-like cells in man. Eight patients had peak postprandial plasma gastrin concentrations greater than 200 pmol/l, which is the 92nd percentile for patients with duodenal ulcer disease in this laboratory. The control group was eight patients with duodenal ulcers whose peak postprandial gastrin concentrations were less than 200 pmol/l. Basal and peak postprandial plasma gastrin concentrations were 107 (37) and 306 (66) pmol/l (mean (SEM] respectively in the hypergastrinaemic patients compared with 26 (4) and 137 (14) pmol/l respectively in the controls. There was no significant difference in the density of gastrin enterochromaffin-like cells between the two groups. The number of enterochromaffin-like cells per high power field was 53 (8) in the hypergastrinaemic patients compared with 50 (8) in the controls. We conclude that chronic moderate hypergastrinaemia does not produce hyperplasia of enterochromaffin-like cells in man. Our hypergastrinaemic group had plasma gastrin concentrations similar to, or greater than those reported during treatment with drugs such as omeprazole and histamine H2 receptor blockers. PMID- 2311973 TI - Effect of prefeeding lipid on food intake and satiety in man. AB - Experiments were carried out in normal volunteers to investigate whether preingestion of lipid reduces food intake. In the first set of experiments, 300 ml beef consomme soup with or without 60 g margarine was fed to each of six volunteers, followed 20 minutes later by either a low fat solid meal or a preselected appetising meal. Subjects were allowed to eat as much of the meal as they wished. Preingestion of the high fat soup had no significant effect on the consumption of either of the solid meals and did not influence sensations of hunger or fullness. As we have previously shown that prefeeding a fatty soup delays gastric emptying of a subsequent meal, this suggests that gastric distension may play a relatively minor role in regulating food intake. In the second set of experiments, we studied the effect of ingesting either a high fat breakfast (65 g fat, 927 kcal) or a similar low fat breakfast (8-1 g fat, 418 kcal) on the consumption of a preselected appetising lunch in six healthy volunteers. The high fat breakfast significantly reduced the amount of the meal eaten at lunchtime (p less than 0.02), the total energy intake from the meal (p less than 0.05) and the rate of eating (p less than 0.05) compared with the low fat breakfast. When the subjects were presented with their lunchtime meal they felt significantly less hungry after the high fat breakfast (p less than 0.05). Only a small proportion of either meal (15% of the high fat meal v 12% of the low fat meal) remained in the stomach and plasma glucose concentrations had returned to fasting levels. Plasma triglyceride concentrations were much higher at lunchtime after ingestion of the high fat breakfast (p<0.001). The energy intake from the breakfast and lunch combined was not significantly different on the high fat breakfast day, indicating that the energy consumption at lunch compensates for the amount eaten at breakfast. These results are compatible with the concept that the interaction of nutrients with small intestinal receptors may play a part in limiting food intake. PMID- 2311974 TI - Diarrhoea of famine and malnutrition--investigations using a rat model. 2--Ileal hypersecretion induced by starvation. AB - The effects of progressive starvation for up to three days on the basal and secretagogue stimulated secretory functions of the rat ileum were investigated in vitro and in vivo. The secretagogues used included agents acting via cyclic AMP (dibutyryl cyclic AMP, theophylline, forskolin, and PGE2) and those acting via Ca++ (acetylcholine, bethanecol, carbachol, 5-hydroxytryptamine, and A23187). Starving rats for 24 h (day 1) had no effect on the basal electrogenic secretion (measured as the short circuit current, Isc muamps/cm2) or on the stimulated maximum electrogenic secretion (measured as the delta Isc where delta Isc = maxIsc-basal Isc). By day 2 of starvation, however, both the basal Isc and the delta Isc induced by all the secretagogues were significantly greater than in the fed and increased even more on day 3. Replacement of all the chloride ions and inhibition by furosemide indicated that the enhanced secretion was due mainly to chloride ions. Cholinergic stimulation was blocked by atropine, indicating the stimulation was via muscarinic receptors while cholinergic dose - delta Isc response curves for fed and starved ilea showed significantly increased maximum electrogenic secretory response in the latter but no evidence of any change in the affinity (ED50) of the receptors mediating the response. The basal secretion and the secretory response to acetylcholine in both fed and starved ilea was unaffected by tetrodotoxin, revealing that the enhanced secretory response could be expressed via the muscarinic receptors on the enterocytes without the enteric neural network. Measurement of ileal fluid movement in vivo showed that in fed and day 1 starved rats the basal, unstimulated 'tone' of the ileum was absorptive. On day 2, however, the basal 'tone' had reversed to one of secretion which increased further on day 3. Stimulation of fluid secretion in vivo by bethanecol, carbachol, or PGE2 induced larger increases in the starved ilea by day 2 which increased even further on day 3. Lumenal chloride and bicarbonate concentrations were greater in the starved ileal fluid than in the fed. The studies in rat ileum confirm and extend those on rat jejunum and indicate that starvation creates a hypersensitive small bowel that responds to secretagogues and cholinergic neurotransmitters with a greatly enhanced secretory response. PMID- 2311975 TI - Why do patients with ulcerative colitis relapse? AB - To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis. PMID- 2311976 TI - Toxic oxygen metabolite production by circulating phagocytic cells in inflammatory bowel disease. AB - To investigate the possibility that the oxidative capacity of phagocytic cells may be defective in inflammatory bowel disease, toxic oxygen metabolite production by circulating neutrophils and monocytes has been measured by luminol dependent chemiluminescence. Neutrophils from patients with Crohn's disease and ulcerative colitis produced significantly lower chemiluminescent responses after chemotactic stimulation with formylmethionylleucylphenylalanine (fMLP) than neutrophils from control patients, p = 0.018 and 0.043 respectively. Chemiluminescent responses of neutrophils from patients with inflammatory bowel disease, however, were similar to control responses when cells were stimulated with latex beads or phorbol myristate acetate. Monocytes from patients with Crohn's disease produced significantly greater levels of chemiluminescence than control monocytes when stimulated with either fMLP (p less than 0.002), phorbol myristate acetate (p less than 0.0005) or latex beads (p less than 0.002). Monocytes from patients with ulcerative colitis also produced significantly greater levels of chemiluminescence than controls when stimulated with latex beads (p less than 0.5) or phorbol myristate acetate (p less than 0.0005), although there was no difference in the level of chemiluminescence in response to fMLP. These results exclude a generalised defect in phagocytic cell oxidase activity in inflammatory bowel disease and suggest that circulating monocytes are 'activated'. PMID- 2311977 TI - Development of colonic sodium transport in early childhood and its regulation by aldosterone. AB - Aldosterone is important in the regulation of sodium conservation by both kidney and colon. In the very preterm neonate marked urinary salt wasting occurs because of immature renal tubular function, but little is known of the ontogeny of colonic transport processes. Using an in vivo rectal dialysis technique, we have shown that in the human infant the colon has well developed salt conserving mechanisms from early in the last trimester of gestation and that aldosterone is an important regulatory hormone. Sodium transport mechanisms in the colon appear to develop before those in the kidney and it is possible that the colon is the major organ of sodium conservation in the preterm neonate. PMID- 2311978 TI - Lactulose inhibits endotoxin induced tumour necrosis factor production by monocytes. An in vitro study. AB - Preoperative oral treatment with lactulose is used to prevent complications after surgery in patients with obstructive jaundice. The effect is perhaps the result of an inactivation of gut derived endotoxins but the exact mechanism of action is, however, unknown. Tumour necrosis factor is an important mediator of endotoxin toxicity. The cytokine tumour necrosis factor is mainly produced by mononuclear phagocytes. In this study, the effect of lactulose on the endotoxin induced tumour necrosis factor release by monocytes was investigated. The direct effect of lactulose on endotoxin was tested in a chromogenic limulus amoebocyte lysate assay. Polymyxin B a known inactivator of endotoxin was used as control in both experiments. Lactulose has a limited capacity to inactivate endotoxin as measured in the endotoxin assay. In contrast lactulose significantly reduced endotoxin induced tumour necrosis factor production by monocytes. In conclusion lactulose inhibits tumour necrosis factor production by a direct inhibitory effect on monocytes, rather than by inactivation of endotoxin. Because tumour necrosis factor is an important mediator of endotoxin toxicity, this inhibitory effect could explain the beneficial effect of lactulose in obstructive jaundice. PMID- 2311979 TI - Intravenous albumin infusion is an effective therapy for hyponatraemia in cirrhotic patients with ascites. AB - The treatment of moderate to severe hyponatraemia in patients with decompensated liver disease is unsatisfactory. We report our preliminary experience using intravenous infusion of albumin to treat this condition. Three patients with cirrhosis, ascites, and hyponatraemia responded satisfactorily to treatment; one patient with fulminant hepatitis B did not respond. Intravenous albumin infusion is a safe and effective therapy for patients with cirrhosis complicated by hyponatraemia. Its main role may be in preparing patients for surgery, particularly liver transplantation. PMID- 2311980 TI - Immunological features of lung lavage cells from patients with primary biliary cirrhosis may reflect those seen in pulmonary sarcoidosis. AB - To investigate the basis of subclinical alveolitis in patients with primary biliary cirrhosis, 10 primary biliary cirrhosis patients were studied by bronchoalveolar lavage. Both bronchoalveolar lavage lymphoid and non-lymphoid cell populations were analysed using immunocytological methods to determine their proportions and phenotypic features in an attempt to gain information as to possible immune mechanisms active in the lung of these patients. Six of the 10 patients in our study showed evidence of an alveolitis (raised lymphocyte count: 27.6 (4.3)% of total count) on lavage. The results were compared with control groups of normal volunteers and patients with active pulmonary sarcoidosis. The six primary biliary cirrhosis patients with lymphocytosis had a raised CD4/CD8 T cell ratio (4.13:1), similar to the sarcoid patients (5.60:1). A proportion of these T-lymphocytes expressed markers of activation (HLA-DR+ 7.5 (2.1)%); CD25 + 2.3 (0.9)%; CD7 + 5.8 (1.5)%. This increased T-cell activation was also seen in the sarcoid groups (HLA-DR+ 10.0 (1.9)%; CD25 + 3.0 (1.1)%; CD7 + 5.0 (0.2)%). This was not seen in the primary biliary cirrhosis patients without lymphocytosis and the normal volunteers. Within the non-lymphoid cell population, an increase in dendritic (RFD1+) cells was seen in primary biliary cirrhosis patients with lymphocytosis (31.2 (1.9)%) and sarcoid patients (46.3 (5.1)%) in contrast with the normal and primary biliary cirrhosis group without lymphocytosis. The primary biliary cirrhosis patients without lymphocytes had a relatively greater proportion of mature phagocytes (RFD7+). We postulate that these observations suggest the emergence in the lung of a granuloma producing mechanism similar to that occurring in the liver. By comparison, the alveolitis found in primary biliary cirrhosis is consistent with that observed in interstitial granulomatous lung disorders such as sarcoidosis. PMID- 2311981 TI - Sclerotherapy in extrahepatic portal venous obstruction. AB - One hundred and twenty two patients who presented with variceal bleeding as a result of extrahepatic portal vein obstruction (EHPO) were entered into the sclerotherapy programme with a mean follow up of 23.69 months (range four to 60 months). Eighteen (14.7%) patients were lost to follow up, three (2.4%) patients underwent surgery, and six (4.9%) patients died. Variceal obliteration was achieved in the remaining 95 patients requiring 5.4 (2.4) sessions of sclerotherapy (range 2-18). Seventeen episodes of upper gastrointestinal bleed occurred in 15 patients during sclerotherapy. Recurrence of oesophageal varices was seen in 15 patients. Ten patients developed bulbous gastric varices after obliteration. Major complications including perforation and strictures were seen more commonly in children. Sclerotherapy was associated with a significant reduction in the bleeding rate (bleeds/month/patient) as compared with the presclerotherapy period (p less than 0.001). Endoscopic sclerotherapy is an effective and safe modality in the prevention of variceal bleeds in patients with extrahepatic portal vein obstruction. PMID- 2311982 TI - Sympathetic activation: a mechanism for morphine induced pain and rises in liver enzymes after cholecystectomy? AB - In patients with biliary type pain after cholecystectomy, morphine often precipitates pain and may induce rises in plasma concentrations of liver enzymes because of exaggerated or prolonged rises in intrabiliary pressure. In this study, changes in plasma concentrations of catecholamines and histamine were determined after the administration of morphine in patients with and without a two-fold or greater rise in the plasma concentration of aspartate aminotransferase at four hours. Those showing rises in aminotransferase had higher concentrations of noradrenaline at 40 and 60 minutes after morphine and higher concentrations of dopamine at 40 minutes after morphine. The two groups had similar concentrations of adrenaline and histamine. Attempts to inhibit rises in aminotransferase after morphine by pretreatment with histamine, serotonin and alpha-receptor blockers were largely unsuccessful, although inhibition was observed with phenoxybenzamine in two of five patients. Higher plasma concentrations of noradrenaline and dopamine before and soon after induction of pain in patients showing rises in aminotransferase are consistent with sympathetic activation but heterogeneity appears to exist in the response to alpha-receptor blockade. PMID- 2311983 TI - Electromagnetically generated extracorporeal shockwaves for fragmentation of extra-and intrahepatic bile duct stones: indications, success and problems during a 15 months clinical experience. AB - Electromagnetically generated extracorporeal shock waves (without waterbath) were applied after intravenous premedication with 10-15 mg diazepam and 100 mg tramadol in the treatment of 33 patients (aged 32 to 91 years) with multiple intrahepatic stones (n = 4) or huge common bile duct stones (n = 29, 18-30 mm in diameter), which could not be removed by conventional endoscopy. Stone disintegration was achieved in 70% of common bile duct stones and in all intrahepatic concrements after 800-7500 discharges, which were applied during one (n = 21), two (n = 6) or three sessions (n = 6). Apart from mild fleabite-like petechiae at the side of shock wave transmission no other side effects were observed for a total of 51 procedures. We believe electromagnetically generated shock waves are safe, easy to apply, and relatively effective in the therapy of common bile duct and intrahepatic stones. PMID- 2311984 TI - Hepatic biliary lipid secretion and gall bladder biliary lipid mass in gall stone patients: effect of ursodeoxycholic acid. AB - We have carried out overnight measurements of hepatic secretion rate and duodenal output of biliary lipids using a duodenal perfusion technique. We correlated these measurements with the fasting state mass of biliary lipids within the gall bladder on the following morning using a combined nasoduodenal intubation and isotope scanning technique. We studied six gall stone subjects before and during treatment with ursodeoxycholic acid 675 mg/day. Lipid mass within the gall bladder correlated with the corresponding overnight hepatic secretion rate for all three biliary lipids. During ursodeoxycholic acid treatment, there was an increase in gall bladder bile acid mass without significant change in cholesterol or phospholipid mass. We conclude that the mass of individual biliary lipids within the fasting gall bladder is influenced by overnight hepatic biliary lipid secretion rate; and that the effect of ursodeoxycholic acid (675 mg/day) on cholesterol saturation index of fasting gall bladder bile is mediated via an increase in bile acid mass rather than through a decrease in cholesterol mass within the gall bladder. PMID- 2311985 TI - Clinical and scintigraphic assessment of the role of endoscopic sphincterotomy in the treatment of sphincter of Oddi dysfunction. AB - Postcholecystectomy pain caused by sphincter of Oddi dysfunction remains a difficult condition to treat. Endoscopic sphincterotomy has been recommended for those patients with confirmed sphincter of Oddi motor abnormalities. We have studied sphincter of Oddi dysfunction patients to evaluate the effects of endoscopic sphincterotomy on both clinical symptoms and previously reported scintigraphic parameters to determine the efficacy of this method of treatment. Nine postcholecystectomy patients (seven women: two men, median age 59 years) with clinical and manometric evidence of sphincter of Oddi dysfunction underwent endoscopic sphincterotomy for persisting biliary type pain. Each patient had scintigraphy before and eight weeks after endoscopic sphincterotomy. The patients symptomatic response was assessed independently at three monthly intervals after endoscopic sphincterotomy. Scintigraphic analysis showed that the TMAX (time in minutes to maximum counts) was significantly reduced from 25.0 (20-36) (median [range]) before endoscopic sphincterotomy to 15.0 (13-25) after endoscopic sphincterotomy (p less than 0.01). Seven of nine (78%) sphincter of Oddi dysfunction patients had significant improvement in their symptoms after a mean follow up period of 12 months (range 6-19) although only six of nine were totally pain free. These results suggest that endoscopic sphincterotomy in manometrically confirmed sphincter of Oddi dysfunction improves bile drainage as measured by quantitative cholescintigraphy and is associated with at least short term symptom relief in the majority of patients. PMID- 2311986 TI - Pathology of common bile duct stenosis in cystic fibrosis. AB - A case of cystic fibrosis complicated by common bile duct stenosis is described. Surgery successfully relieved the obstruction, but was complicated by Candida septicaemia. The previously unreported histological abnormalities of the common bile duct are discussed. PMID- 2311987 TI - Oesophageal carcinoma in Sri Lanka. PMID- 2311988 TI - Acrodermatitis enteropathica with normal zinc concentrations. PMID- 2311989 TI - Helicobacter pylori infection in Meckel's diverticula. PMID- 2311990 TI - Influence of treatment with pancreatic extracts on pancreatic enzyme secretion. PMID- 2311991 TI - Some possible pathological consequences of peptic ulcer therapy. PMID- 2311992 TI - [The spontaneous course of lunate malacia]. AB - The analysis of 114 cases of lunatomalacia illustrates well the natural history of Kienbock's disease. The investigation encounters some difficulties in that the patients have all been treated, whether surgically or not, at different stages of the disease. Thus, lunatomalacia's otherwise spontaneous course has been influenced in one way or another. Although we cannot present cases in which all stages of lunatomalacia can be traced, we have been able to gain valuable insights from our analysis: A remission is possible in the early stage of lunatomalacia. Severe clinical symptoms present upon lunate collapse and particularly upon development of pronounced arthritic changes. One to two years elapse before lunate collapse, whereas the development of arthrosis of the wrist may take from ten to twenty years. Lunate disintegration is followed by carpal collapse, after which clinical symptoms subside. A new staging for lunatomalacia is presented, taking clinical, radiological, biomechanical, and therapeutic aspects into account. PMID- 2311993 TI - Follow-up investigation of fresh lunate bone fracture. AB - In order to evaluate the clinical and radiological aspects of fresh lunate fractures, a follow-up investigation was carried out. In the past thirty-one years (1956-1986), seventeen patients were found to have fresh lunate fractures. Eleven of these cases were clinically and radiologically reexamined, with observation intervals ranging from 1.25 to 31.33 years. The authors found no radiologic evidence of lunatomalacia, osteonecrosis, or osteoarthrosis. Two cases of chip-fractures had not healed, but the bone structure was normal. Clinically, none of the patients presented with pain, muscular atrophy, or reduced power of grip. None of the patients had changed occupation as a result of the fracture. PMID- 2311994 TI - [Kienboeck's disease: comparative study of magnetic resonance tomography and roentgenologic imaging]. AB - Magnetic resonance imagine of the carpus is helpful in diagnosing or ruling out even early stages of lunatomalacia. MRI is capable of providing information on the vitality of the lunate and is thus helpful in developing a proper therapy plan. PMID- 2311995 TI - [Results of treatment of semilunar bone necrosis. A study of 91 patients]. AB - The results of nine different methods for treating patients with lunate necrosis were investigated in a retrospective study. The study included seventy-eight of eighty-two operated patients with an average follow-up of five years and thirteen of thirty-five patients conservatively treated were examined at an average follow up time of nine years. Treatments used were: shortening of the radius, lengthening of the ulna, pisiform transposition, prosthetic replacement, tendon interposition arthroplasty, STT-arthrodesis (scaphotrapezio-trapezoid arthrodesis), denervation of the wrist, wrist arthrodesis, and conservative therapy. The most important criteria for rating the results were pain relief, range of motion, grip strength, and X-ray findings. In the early stages of lunate necrosis with a minus variant of the ulna the best results were obtained by shortening of the radius. In intermediate stages good results could be achieved by tendon interposition arthroplasty. Denervation and STT-arthrodesis can be performed at any stage of the disease and may be combined with other methods. Despite some good results, a search for even better operative methods should continue, because the available techniques, especially in cases of advanced necrosis, do not always lead to satisfactory results. PMID- 2311996 TI - [Acute vascular disorder as a complication of replantation and revascularization of the digital area]. AB - This study on vascular complications in digital replantation and revascularization covers the six-year experience of a universitary replantation center. The material comprises 143 patients with 67 replantations and 137 revascularizations. Inadequate circulation was observed in 21.6% of the cases, or 17.6% of the digits. In digital replants, during or following the initial surgery, significant vascular complications were encountered in 28 (42%) of the replanted thumbs and fingers. Of these, seven digits (10.4%) presented with irreparable vascular damage and were amputated without salvage attempts. Single or repeated microvascular revisions saved 13 (two thirds) of the remaining digits. The survival rate of this group was thus raised to 78%. In digital revascularization, the vascular complication rate was much lower. In 137 digits, eight developed complications (6%). One of these was accepted as a failure; of seven reinterventions, five proved successful. The over-all survival rate was 98% in this group. To the factors known to determine survival following replantation and revascularization, those governing the ability to offset vascular complications must be added. In this respect, the analysis of our data revealed additional statistically significant prognostic elements: the decision for or against surgical reintervention, the location of the thrombosis relative to the arterial or venous side, the type of injury and the timing of revisional surgery. Other parameters, such as the age of the patient, the experience of the surgeon, or the type of initial vascular reconstruction were not statistically relevant. In our experience, repeated attempts at microvascular salvage in face of circulatory complications of digital replantations or revascularizations are worthwhile. PMID- 2311997 TI - Hemangioma of the fingers. AB - Fingers often suffer trauma and the clinician is continuously faced with the difficult task of clarifying the distinction between a hemangioma and a traumatic lesion. This study was undertaken to examine ten cases in which a small skin mass located on a finger had been diagnosed preoperatively as hemangioma. Our results showed that seven masses were confirmed pathologically as hemangioma (five cavernous hemangiomas and two capillary hemangiomas), two as traumatic thrombosis and one varix. The clinical manifestations of the two cases of traumatic thrombosis were related to those of hemangioma. In the varix, endothelial proliferation was observed in the area of the thrombosis. This phenomenon is called "intravascular papillary endothelial hyperplasia", and can confuse the differential diagnosis between a vascular neoplasm and a traumatic thrombosis. Our findings demonstrate that since the traumatic lesions were firmer than the hemangiomas, hardness on physical examination may be a helpful indicator in the differential diagnosis of a hemangioma and a traumatic lesion. PMID- 2311998 TI - [The abductor digiti minimi longus muscle as a cause of distal ulnar compression syndrome]. AB - The authors report a case of ulnar nerve compression caused by an abductor digiti minimi longus. After resection of the muscle the patient recovered well. PMID- 2311999 TI - [Struggle for the image of internal medicine in Israel]. PMID- 2312001 TI - [Is intensive therapy of diabetes advisable?]. PMID- 2312002 TI - [Physicians, old age and blood donation]. PMID- 2312000 TI - [Subcutaneous fat necrosis of the newborn]. PMID- 2312003 TI - [Treatment of acute myeloid leukemia in a special hematology unit]. AB - Since 1984, 47 patients with untreated acute myeloid leukemia (AML) were hospitalized in a special hematology unit for aggressive chemotherapy. Complete remission was obtained in 68%, 15% died of complications of treatment (infections and bleeding) and 15% had refractory leukemia. The actuarial survival after 3 years for patients in remission was 43%. No patients with refractory leukemia lived more than 1 year. The actuarial remission at 3 years of 21 patients who received additional courses of aggressive chemotherapy (consolidation treatment) was 42%, as opposed to 11% in 11 patients who received maintenance treatment. The 47 patients received 108 courses of aggressive chemotherapy including 47 for induction of remission. During 86 courses (80%) the patients developed fever and in 33 blood cultures were positive; during 16 courses a fungal infection developed. The most common bacterial infection was by E. coli. During the first induction treatment 5 patients died of sepsis and 1 of cerebral hemorrhage. None died during consolidation therapy. During the year preceding the opening of the unit, 12 AML patients were treated on regular medical wards, and five (42%) achieved a complete remission, while 6 died of complications during the first course of induction chemotherapy. Our findings are in line with those of similar units, which indicates the importance of special nursing units for the treatment of acute leukemia. PMID- 2312005 TI - [Decreased bone marrow cellularity and hemosiderin in normal and overtrained runners]. AB - The frequency and significance of decreased bone marrow cellularity (BMC) and bone marrow hemosiderin (BMH), and their possible relations to hemoglobin, iron, iron saturation and serum ferritin levels, were studied in 18 normally trained and 18 overtrained competitive distance runners. Decreased BMC was more pronounced in the overtrained runners: mild to moderate hypocellular marrow was found in 25% of them, and severe hypocellularity in another 25%, as compared to 18% and 3.5%, respectively, in the healthy runners. Increased erythrocyte mean corpuscular volume (greater than 95 mu 3) was found in 24% of the runners, but in only 3.5% of the controls. Decreased BMH was found in both the overtrained (1.3 +/- 2.0 hemosiderin granules per 100 normoblasts) and the controls (1.5 +/- 1.9 granules). There were no significant differences in levels of hemoglobin, mean corpuscular volume and serum iron, iron saturation and ferritin. The decreased BMH in the face of normal hemoglobin and serum iron and ferritin suggests that as a group, competitive distance runners do not suffer from overt iron deficiency but that iron might be stored differently, with a lesser proportion in the bone marrow. The more pronounced decrease in BMH of overtrained distance runners may indicate a possible relationship, and decreased BMC may identify runners who may be becoming overtrained. PMID- 2312004 TI - [Treatment of aplastic anemia with antithymocyte globulin]. AB - Acquired aplastic anemia is usually fatal. During recent years autoimmune disturbances have been implicated in bone marrow depression. This has led to a novel therapeutic approach based on immune suppression to enable bone marrow recovery. We report 4 adult patients who were treated with antithymocyte globulin. PMID- 2312006 TI - [Hepatotoxicity of oriental hornet venom]. AB - Reports of hepatic damage following multiple stings by hornets led to this study of the effects of venom sac extract (VSE) from the oriental hornet. We used in vivo models (serum of cats following a single exposure, and of rats following repeated exposures), in-situ models (perfusion of intact livers) and in-vitro models (monolayers of fetal rat liver tissue culture). Enzyme activities were measured in serum, in perfusates, and in media of cultures, as well as in liver fractions obtained by ultracentrifugation. In cats, levels of albumin, total proteins, electrolytes, urea, cholesterol, bilirubin and blood gases were determined. Bile acids were determined in bile secreted from perfused rat livers. Histologic, histochemical and electron-microscopic studies were also performed. It is concluded that VSE is the first animal product known to possess hepatotoxic properties. The venom mainly damages hepatic cellular membranes, and mitochondria are the organelles most severely injured; cholestasis also results. The damage is partially reversible, and occurs in mammals, including man. PMID- 2312007 TI - [Malignant angioendotheliomatosis]. AB - Malignant angioendotheliomatosis is one of the terms used to describe the appearance of neoplastic cells resembling endothelium within the lumen of small and medium-sized blood vessels, mainly in the cerebral and meningeal vascular beds. A fatal systemic disease with dementia as the leading neurological manifestation may be associated with these pathological findings. Only recently has it become evident that this disease is a unique intravascular form of large cell lymphoma, affecting mainly the cerebral blood vessels but also present in the lumen of many small and medium-sized blood vessels in the systemic circulation. PMID- 2312009 TI - [Alcohol-related admissions in a community hospital]. AB - We reviewed 150 alcoholic patients (1.3% of all admissions) hospitalized in this department during 1983-1987 and compared them with a random sample of 450 other patients in the department during the same period. In the alcoholic group were more males, an increased prevalence of those of Yemenite and Indian origin, and a higher rate of unemployed. The clinical presentation was heterogenous. In 26% of the chronic alcoholics no abnormality related to alcoholic injury was detected. The other patients in that group suffered from a variety of clinical problems related to alcohol. In 41% the immediate cause of admission was related to chronic alcoholism, and in others (31%) we observed alcohol-related pathology in addition to the main cause of hospitalization. We wish to increase awareness of the medical problems of chronic alcoholics encountered in a community hospital in order to promote quicker diagnosis, avoid unnecessary diagnostic procedures, and lead to better medical care. PMID- 2312008 TI - [Transient hypophosphatemia associated with hairy-cell leukemia]. AB - A 43-year-old man with hairy-cell leukemia and marked splenomegaly developed severe hypophosphatemia which improved after splenectomy. Since splenic tissue phosphorus was significantly elevated, and since serum phosphorus returned to normal levels immediately after the operation, it is postulated that excessive uptake of phosphorus by the rapidly dividing leukemic cells might have caused the transient decrease in serum phosphorus. PMID- 2312010 TI - [Trends in undergraduate medical education]. PMID- 2312011 TI - Embryotoxicity/teratogenicity of isomalt in rats and rabbits. AB - The embryotoxicity/teratogenicity of the sugar replacer isomalt was studied in Wistar rats and New Zealand White rabbits. Groups of 22-23 female rats were given diets containing isomalt at concentrations of 2.5, 5 or 10%, from day 0 to day 21 of pregnancy. The possible adverse effects of restricted feeding were studied in an additional group (food intake less than 80% of the control values). Groups of 36-37 female rabbits were given diets containing isomalt at concentrations of 2.5, 5 or 10%, from day 0 to day 29 of pregnancy. The female rats and rabbits were killed on days 21 and 29 of pregnancy, respectively. In both species no maternal toxicity occurred and no effects on reproductive performance nor on embryonic or foetal development were seen in any of the groups fed isomalt. The feeding of restricted amounts of stock diet to pregnant rats resulted in decreased maternal weight gain and lower uterus weights. Furthermore, this group had an increased number of resorptions and small foetuses, decreased foetus and placental weights and retarded bone development. PMID- 2312012 TI - Uptake of the naturally occurring 3-alpha-hydroxy isomer of T-2 toxin by a murine B cell hybridoma. AB - The uptake of the naturally occurring 3-alpha-hydroxy isomer of T-2 toxin (alpha T-2 toxin) was investigated in a murine B cell hybridoma as a model for trichothecene-lymphocyte interactions. alpha-[3H]T-2 toxin was prepared by oxidation of T-2 toxin and reduction with [3H]NaBH4 followed by normal phase and reverse phase high-performance liquid chromatography. Uptake of alpha-[3H]T-2 toxin by hybridoma cells was both time- and concentration-dependent. The antibiotic anisomycin inhibited uptake of alpha-[3H]T-2 toxin by hybridoma cells, which suggests ribosomal involvement in the uptake mechanism. Uptake of alpha [3H]T-2 toxin was also inhibited by verrucarin A, roridin A and deoxynivalenol, and the inhibition followed a trichothecene structure-activity rank similar to that established for protein synthesis inhibition and in vivo toxicity. The characteristics of uptake of alpha-[3H]T-2 toxin by isolated splenocytes were qualitatively similar to those of the hybridoma but accumulation at equilibrium was less. Accumulation of alpha-[3H]T-2 toxin by erythrocytes, cells lacking ribosomes, did not increase with time and was not affected by the presence of unlabelled toxin. The results suggested that specific accumulation and uptake of alpha-[3H]T-2 toxin by the murine B cell hybridoma and spleen cells were highly consistent with a model based on intracellular binding of T-2 toxin to ribosomes. PMID- 2312013 TI - Oncogenicity study of macrodantin in Swiss mice. AB - A carcinogenicity study of nitrofurantoin formulated as Macrodantin was undertaken. The doses used were 0.0, 50.0, 100.0 and 200.0 mg/kg/day. Increased mortality was observed in male mice given 200 mg/kg/day. Chronic toxicity was observed in the kidneys of male mice: the normally occurring chronic nephropathy was somewhat increased in severity. The gonads of both male and female mice showed evidence of atrophy and degeneration. The ovaries showed an increased incidence of multilobular cysts but no evidence of neoplasia. A significantly higher incidence of malignant lymphoma in the top-dose males was offset by a non significant difference in the opposite direction in females. Reasons are given for regarding this as a chance finding. The observations in this study indicate that the therapeutic uses of nitrofurantoin would not present a carcinogenic hazard to man. PMID- 2312015 TI - Nitrosamines, food and cancer: assessment in Lyon. PMID- 2312014 TI - 90-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat. AB - Musk ketone, musk xylene, musk tibetene and moskene, synthetic musks used in fragrances, were applied dermally to rats in daily doses of 240 (musk ketone and musk xylene only), 75, 24 or 7.5 mg/kg body weight for 90 days. The chemically related musk ambrette, a known neurotoxin in rats, was used as a positive control. While musk ambrette was clearly neurotoxic and caused testicular atrophy, as had been previously reported, the other compounds tested caused neither effect. The only effects of application of these materials were some organ weight changes at the higher doses, but these were not associated with histopathological changes in any of the tissues. The no-effect levels were: musk ketone, 75 mg/kg for males and females; musk xylene, 75 mg/kg for males and 24 mg/kg for females; moskene, 24 mg/kg for males and 75 mg/kg (highest dose administered) for females; and musk tibetene, 75 mg/kg (highest dose) for males and females. PMID- 2312016 TI - [Experiences with Burstone's segmented arch technic in the adult dentition]. AB - In comparison to the straight wire technique the segmental arch approach offers numerous biomechanical and clinical advantages. Three typical examples: controlled tooth movement, en masse space closure and deep overbite correction serve to show the spectrum and the efficiency of the segmented arch technique. PMID- 2312017 TI - [The treatment of adults with removable appliances? A contribution to orthodontic prosthetic collaboration]. AB - Request of adults for orthodontic treatment increases. In that cases requirements to the practitioner are of many kinds, especially if in consequence of secondary changes after lost of teeth the patient is not able, as in the past to accept his irregularities of teeth in relation to masticatory, physiognomic and phonetic function. Absolutely there is willingness to wear also removable orthodontic appliances. Possibilities and advantages of plates for orthodontic-prosthetic problems are discussed and examples of treatment demonstrated. PMID- 2312018 TI - [Changes in the functional status of the stomatognathic system due to orthodontic multiband treatment in the adult]. AB - Ten patients who undergo an orthodontic therapy with a full-band modified straight-wire-appliance were examined clinically and by means of an electronic axiographic device (SAS-system) at the beginning of treatment and after an average of 12.6 months, respectively. While the clinical functional status showed only minor changes, alterations of all examined axiographic parameters could be detected. This finding reemphasizes the necessity of modern axiographic means to get additional information about the functional status of the TMJ. The alterations point to a shift in the functional pattern of articular and muscular components during orthodontic treatment. In the majority of cases, axiographic parameters remained constant, however. In that respect, it might be of special interest that even uncoordinated tracings, mainly in the horizontal plane, kept up its characteristic appearance. These findings show clearly, that alterations of occlusal relationships must not influence articular functional patterns immediately. PMID- 2312019 TI - [The treatment of deep bite in adults]. AB - 49 treated adult patients with deep-bite were classified by analysing orthodontic models and lateral cephalograms differentiating skeletal, dento-alveolar deep bite and class I, class II-1, class II-2 malocclusion. Change of overbite and position of incisors were described within every group and compared with the other groups. RESULTS: On the average overbite decreased about 3.5 mm, mostly however combined with root resorptions in the maxillary front. After removing the appliance overbite relapsed about 1.7 mm at 93.3% of cases. The percentage of factors which made possible a decrease of overbite was described and parameters which caused the relapse were discussed. Interpreting the results of orthodontic treatment in adults, it seems to be legitimized in some exactly indicated cases but, treatment in adults is not the best time for correcting deep-bite. PMID- 2312020 TI - [The experiences of adult patients with their orthodontic treatment]. AB - Own experience with an orthodontic treatment stimulated us to interview patients out of retention about four topics concerning their opinion and experience: 1. Reasons for treatment, 2. doubts about treatment, 3. troubles during treatment, 4. attitude to the result of treatment. 50 adults, former patients of the Department of Orthodontics at the Erlangen-Nurnberg University, responded our questionnaire. Aesthetics range first in the patient's desires for treatment. Severe doubts about treatment rarely occurred before treatment. The occurrence of particular complaints cannot be predicted and does not show a characteristic distribution. Pain, induced by treatment generally was underrated. For unpredictable severe pain may occur, one might consider to review the treatment goals critically after the patient's own experience with orthodontic treatment. PMID- 2312021 TI - [The psychology of the treatment of adults]. AB - In this paper the different psychological aspects of adult orthodontic treatment are discussed based on our own experiences and results of an investigation. PMID- 2312022 TI - [What clinical significance do antibodies to drugs have? Side effects are as possible as ineffectiveness]. PMID- 2312023 TI - [Drug prevention of stress for all--what prevents it? Comments on the borderline between philosophy and medicine]. PMID- 2312024 TI - [Treatment of restless legs]. PMID- 2312025 TI - [AIDS. No reason to give the all-clear signal]. PMID- 2312026 TI - [In thyrotoxic crisis, immediate volume therapy. Iodine-containing drugs are the leading cause]. PMID- 2312028 TI - [AIDS: prevention of pulmonary complications. Pneumocystis carinii pneumonia- mycobacterial infections]. PMID- 2312027 TI - [Unconsciousness--coma--apallic syndrome. 1: Diagnosis and differential diagnosis]. PMID- 2312029 TI - [Pain syndromes following amputation. Analysis of 100 affected patients with chronic stump and phantom pain]. AB - One hundred amputees (m = 95, f = 5) with a pain syndrome were analysed. In 80 patients post-amputation pain of the lower, in 20 of the upper, extremities presented. Thirty-two patients suffered bouts of pain, 68 constant pain of various types. The most commonly cited type of pain in the patients with intermittent pain was lancinating, in the case of constant pain a burning sensation. In some patients pain occurred immediately after the loss of the limb, in others not until several years, or even decades, later. Forty per cent of our patients indicated that the incidence and intensity of the pain increased with time. Neurological, orthopedic and internistic causes of stump or phantom pain have been described. In 72% of the patients with constant pain and in 34% of those suffering from bouts of pain, an algogenic psychosyndrome had developed. Complications and late sequelae of amputations are of considerable significance for the development and intensity of stump and phantom pain. PMID- 2312030 TI - [Pain symptoms in paraplegic patients]. AB - The number of paraplegics who survive their initial trauma by decades is on the increase. A considerable percentage of these patients will, sooner or later, temporarily or permanently, manifest a pain syndrome and/or phantom pain. Accurate differentiation of the disagreeable sensations, which are often difficult to describe (dysesthesia, paresthesia), is frequently a big problem. The pathogenesis still remains unclear, and therapy often proves unsatisfactory. PMID- 2312031 TI - [Unconsciousness--coma--apallic syndrome. 2: Principles of therapy]. PMID- 2312032 TI - [HMG-CoA reductase inhibitors in familial hypercholesterolemia. Therapy with simvastatin alone and in combination with cholestyramine in low dosage; a report of 2 years experiences]. AB - We have studied the effect of simvastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, alone and in combination with cholestyramine in 48 patients. Simvastatin 40 mg decreased total serum cholesterol, LDL cholesterol and apolipoprotein B by 35%, 40% and 35%, respectively, while HDL cholesterol and apolipoprotein A-I increased by 10% (p less than 0.01) and 7% (p less than 0.05), respectively. The addition of 8 g cholestyramine caused a further decrease in total cholesterol and LDL cholesterol to a total of 42% and 49%, respectively. Eighteen of the 48 patients have now been under combined treatment for 2 years. The initial high decreases in total cholesterol and LDL cholesterol were stabilized for the whole period. Some patients developed gastrointestinal complaints, which made necessary a reduction of simvastatin in two cases. Biochemical side effects (e.g. increases in CK and transaminases) were not observed. PMID- 2312034 TI - Hypertension as a risk factor for sudden cardiac death and nonfatal myocardial infarction. Working Group of CNR Study OD1. AB - To evaluate long-term prognosis during medical treatment of hypertension associated with angina pectoris, a total of 1083 patients with angiographically documented coronary artery disease were followed for a mean of 66 months. At the end of the study, follow-up was complete in 98% of all patients. Of the 1083 patients, 132 (12%) had hypertension and 951 (88%) were not hypertensive. During the follow-up period, there was a total of 15 deaths (11.3%) among the hypertensive population (vs. 61 or 6.4% in the nonhypertensives) as well as a higher incidence of nonfatal myocardial infarction (9.0% in the hypertensives vs. 3.7% in the nonhypertensives) (Figure 2). Six-year cumulative survival was 84% in the hypertensive patients as compared to 92% in the nonhypertensives. Among risk factors, historical data, clinical and catheterization findings, the only noninvasively-obtainable independent predictor of prognosis using multivariate analysis was hypertension (Table 3). PMID- 2312033 TI - [What is the value of high resolution electrocardiography in the identification of patients at risk?]. AB - Sudden cardiac death occurs in the Federal Republic of Germany with an incidence of 60,000 to 90,000 per year. Ambulatory ECG monitoring has demonstrated that in about 80% of such events, the heart rhythm before and during sudden cardiac death shows ventricular tachycardia leading to ventricular fibrillation and circulatory standstill. From experimental studies it is known that the substrate for precipitation of the ventricular arrhythmia is localized injury in myocardial tissue with conduction delays and conduction blocks resulting in inhomogeneous spread of the impulse between normal and injured myocardium enabling the existence of an electrical re-entry circuit. Anisotrophy, that is differing velocities of conduction parallel and perpendicular to fiber direction as well as dispersion of repolarization appears responsible for propagation of the circuit. Because of the delayed impulse spread, the late depolarization after the end of the QRS complex can be detected in the ECG as ventricular late potentials by means of high resolution systems. Ventricular late potentials may be regarded as indicative of increased electrical vulnerability of the ventricles. Prevalence of ventricular late potentials: In our own studies using the signal-averaged ECG technique, ventricular late potentials were found most frequently in patients with coronary artery disease and only in 6/100 healthy subjects, in 5/30 patients with dilated cardiomyopathy, in none of 30 patients with aortic stenosis or ten with "small vessel disease". With continuously-registered high resolution electrocardiography but not with the signal-averaged ECG, patients with dilated cardiomyopathy or QT-syndrome can be found to have labile, intermittent ventricular late potentials. In patients with coronary artery disease, the number of those in whom ventricular late potentials can only be detected with continuously-registered high resolution ECG in addition to signal-averaged technique lies between 6 and nearly 30%. With respect to frequency analysis of the ST-segment, which is based on the hypothesis that the fractionated signals in arrhythmogenic areas are of higher frequency than the normal low frequency signals of the ST-segment in normal myocardial areas, there is only limited experience and no data from larger collectives.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2312035 TI - Analysis of a prospective series of 100 mesocaval interposition shunts for bleeding portal hypertension. AB - The results of a prospective series using the mesocaval interposition shunt (MIS) over a period of 13 years is reviewed. One hundred patients were selected for the operation using strict criteria, and in 98 cases the operation was performed electively. Selection criteria included a liver volume of between 1,000 and 2,500 ml, portal perfusion of between 15-30%, no active liver disease and no stenosis of hepatic artery or celiac axis, as well as a good functional Child-Pugh classification (A-B). In all the cases preoperative sclerotherapy was performed as many times as needed with the aim of controlling the active bleeding at admission and of diminishing the pre- and postoperative bleeding probability. Intra-operative postshunt measurements showed residual portal perfusion in all patients studied. Early mortality was 10% and the follow-up mortality 38.8%. The main causes of death were liver failure and hepatocellular carcinoma. The five- and ten-year survival rates were 65% and 35%, respectively. The total encephalopathy rate was 12.2%. Rebleeding was observed in 5.5% of the cases, and the long term-shunt patency rate was 90%. Anigography and sequential scintigraphy showed residual portal perfusion in 75% of the cases soon after operation, in 60% after 6 months, and in 38% after 2 years, showing the tendency of the diversion to diminish the portal perfusion rate in the late postoperative period. The results show that MIS still has a place in the treatment of portal hypertension and that it is an excellent alternative choice to the selective shunts and the devasculariaztion procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312036 TI - Endoscopic therapy and early elective operation as a therapeutic regimen in ulcer bleeding. AB - In a prospective protocol we treated 63 consecutive patients admitted to our surgical department with bleeding gastroduodenal ulcers between January 1986 and December 1987. The therapeutic regimen included emergency endoscopy in all cases. Active Forrest Ia or II hemorrhage was treated endoscopically with submucosal injection. Endoscopic control of hemorrhage was achieved in all but one case. Low risk ulcers, e.g. Forrest II without visible vessel and III or ulcers caused by antirheumatic drug medication were treated definitively by therapeutic endoscopy (31 patients). Ulcers with high risk of rebleeding even after endoscopic therapy underwent additional early elective operation. Thirty patients were treated surgically by this means. Two patients required emergency operation because of failure to control the bleeding (Ia and second rebleeding) endoscopically. The overall mortality of the surgically treated patients was 6% (2/32). The mortality of the therapeutic endoscopy was 0%. Thus, the mortality of the overall group was 3%. The major advantages of this concept were: low mortality rates, elimination of rebleeding in the follow-up period, optimal conditions for the surgical therapy resulting in low death-rates and a reduced need for transfusions. PMID- 2312037 TI - Effects of plasma exchange (PE) in primary biliary cirrhosis (PBC). A pilot study. AB - Six patients were studied to evaluate the efficacy and safety of plasma exchange (PE) in the treatment of primary biliary cirrhosis (PBC). All patients were affected by PBC at stage III-IV and presented symptoms refractory to pharmacologic therapy. Patients underwent PE for a mean period of 40 weeks (range 10-88). A mean of 33 liters (range 17-64) of plasma per patients was removed. Patients reported less fatigue (4/6), pruritus (5/5), nausea (3/3), Sjogren's syndrome (2/6), and painful neuropathy (2/3). A reduction of xanthomata was noted in one of the three affected patients. Definitive improvement was seen in the patient with Raynaud's phenomenon. A significant reduction was noted for serum cholesterol and gammaglobulins. ALT, AST, gamma-GT, alkaline phosphatase, bilirubin, prothrombin activity, AMA titers were not affected by PE. All patients suffered some mild adverse effects during PE. Two patients (IV stage) developed late edema and ascites after 34 and 44 weeks of treatment. We conclude that PE can be considered effective chronic treatment for advanced symptomatic PBC refractory to pharmacological therapy. PMID- 2312038 TI - The influence of severe bulb deformity on duodenal ulcer relapse. AB - In order to evaluate the prognostic role of duodenal bulb deformation in the recurrence of peptic ulcer, duodenal bulb morphology and the complete healing of duodenal ulcer were endoscopically evaluated in sixty patients, who were subsequently allocated at random to either maintenance therapy with ranitidine or no treatment. Endoscopic checkups were done at regular intervals, up to the first ulcer recurrence. As expected, long-term ranitidine treatment significantly reduced the relapse rate (12 month cumulative relapse rate was 32% versus 86% in the untreated). A set of prognostic factors which might interfere with this result (sex, age, alcohol consumption, history of ulcerous relatives, duration of the disease, previous H2-blocking treatment, previous complications, smoking and morphology of the duodenal bulb) were evaluated by multivariate analysis using the Cox regression model. Only duodenal bulb morphology appeared to have any independent prognostic value. In the untreated group ulcer recurrence seemed to occur earlier (median relapse time = 2 months) in the patients with severe non stenosing bulb deformity, and later in those with normal or mildly deformed bulb (median relapse time = 8 months); ranitidine treatment delayed relapse in deformed bulb patients (median relapse time = 14 months) and almost eliminated it in those with normal duodenal bulb morphology. No association was found between the presence of duodenal bulb deformity and the above-mentioned covariates. Our study confirms the primary importance of anti-H2 treatment and suggests that anatomical characteristics of the duodenal bulb also influence the occurrence of ulcer relapse. PMID- 2312039 TI - Characteristic pattern of free amino acids in plasma and skeletal muscle in stable hepatic cirrhosis. AB - Free amino acid (AA) concentrations in plasma and quadriceps femoris muscle were determined in 19 healthy volunteers and in 16 patients with hepatic cirrhosis and portal hypertension. Nutritional state was impaired as judged by overt muscle wasting (9/16), triceps skinfold thickness less than 70% of normal in 8/14 (57%), and creatinine-height index below 70% in 5/12 (42%). In the plasma of patients the typical amino acid pattern of cirrhosis was to be observed: Elevation of tyrosine and methionine (p less than 0.01), uniform reduction of branched chain amino acids (p less than 0.001) resulting in a decreased molar ratio of BCAA/AAA from 2.85 +/- 0.05 in normal individuals to 1.35 +/- 0.12 in cirrhotics (p less than 0.001). Levels of the gluconeogenic AA glutamine, glutamate, aspartate, alanine, glycine, threonine, serine and lysine were lowered (p less than 0.05). In muscle of cirrhotics, intracellular AA concentrations exhibited a similar pattern with two major exceptions: Tyrosine and phenylalanine were augmented (p less than 0.001). Surprisingly, BCAA levels were altered heterogeneously; those of gluconeogenic BCAA decreased: Valine from 0.34 +/- 0.03 to 0.20 +/- 0.03 mmol/l (p less than 0.001), isoleucine 0.09 +/- 0.01 to 0.05 +/- 0.02 mmol/l. However, the concentration of ketogenic leucine remained unaltered in muscle. Nevertheless, the molar ratio of BCAA/AAA was considerably reduced from 3.70 +/- 0.04 to 0.81 +/- 0.08 (p less than 0.001). Most of the gluconeogenic AA exhibited reduced intramuscular concentrations, but glutamine levels were normal. The pattern of plasma and muscle free AA in hepatic cirrhosis is thus characterized by accumulation of aromatic AA and by depletion of gluconeogenic AA, especially BCAA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312040 TI - Diagnostic and pathogenetic implications of urinary coproporphyrin excretion in the Dubin-Johnson syndrome. AB - The Dubin-Johnson syndrome (DJS), a hereditary conjugated hyperbilirubinemia, is associated with an impairment of porphyrin metabolism. Total urinary coproporphyrin (CP) excretion and the urinary CP isomer I and III constellation were examined in 15 patients with DJS and 12 unaffected family members, and then compared with 50 unrelated control persons (55 +/- 15 nmol/24 h of total CP: 27 +/- 3% of isomer I; +/- SD). The patients with DJS excreted 80 +/- 7% (+/- SD) of CP isomer I (p less than 0.001). The isomer relation in two young children, 3 and 5 years old, shows an isomer reversal, with isomer I of about 95%. Studies done on four families from our patients with DJS indicate and confirm the autosomal recessive mode of inheritance. Total urinary CP was found to be elevated in subjects with DJS, reaching a mean value of 164 +/- 123 nmol/24 h (upper limit 120 nmol/24 h). Fecal CP isomers I and III were found to be in the usual physiological proportion to each other, but total fecal CP excretion had declined to the lower normal level (10 +/- nmol/g, n = 8). The pathogenetic mechanisms in DJS have not yet been fully worked out. Four possible explanations are currently under discussion: 1. an impaired hepatic excretory function: 2. a uroporphyrinogen III synthase defect; 3. an increase in porphobilinogen deaminase (uroporphyrinogen synthase) activity, or 4. a membrane-associated transport disorder with secondary metabolic changes of the isomer pool and enzyme activities. PMID- 2312041 TI - Pancreatitis could be one of the extra-intestinal manifestations of IBD. PMID- 2312042 TI - Assessment of in vivo activated T cells in patients with Crohn's disease. AB - Besides clinical indices, acute phase reactants and measurement of permeability of the gut immunological parameters have been proposed for assessment of clinical activity in Crohn's disease (CD). The latter refers in particular to the number of activated peripheral T cells (APT) which are found to be increased in patients with CD and ulcerative colitis. Further analysis of the subset of APT revealed that in CD their number is correlated to the histopathological ratings and the number of activated T cells of the affected mucosa. A major subset of APTs in CD and ulcerative colitis expresses receptors for IgA (Fc-alpha-R). This T cell subset seems to be characteristic of patients with inflammatory bowel diseases, exhibiting a specificity of 88% and a sensitivity of 92% for CD as compared with non-inflammatory bowel diseases. Methodological complexity turned out to be the major disadvantage of assessment of APT and their subsets. PMID- 2312043 TI - Crohn's disease in four members of a family, two of whom are dizygotic twins. AB - Familial occurrence of Crohn's disease (CD) is well known, but the disease is rarely reported to occur in dizygotic twins. We present an additional case of dizygotic twins, both of whom developed CD, from a family in which two other members are affected. The 16-year-old son contracted the disease 2 years before his 50-year-old father, and 13 years before his twin sister. Another sister was affected 6 years after the onset of the disease in the propositus. HLA haplotyping of the three children matched the Mendelian ratio. The multiple occurrence of CD in blood relatives, especially in siblings, emphasizes the importance of genetic factors in the development of this disease. This family history, however, could point to psychic influences promoting the occurrence of CD on the basis of a polygenic disease susceptibility. PMID- 2312044 TI - Gallstones in Crohn's disease. AB - The prevalence of gallstones in 52 patients operated on for Crohn's disease at the University Central Hospital of Tampere over a 17-year period (1972-1988) was 21%, as compared with 23% in an age- and sex-matched control population. The gallstone prevalence rate among patients with Crohn's ileitis was significantly higher than in patients with ileocolitis (p less than 0.05) or patients with Crohn's colitis (p less than 0.005). The prevalence of gallstones in 33 patients with ileal resection was 24%. In patients with an ileal resection of more than 50 cm in length the frequency of gallstones was 33% as against 17% in patients with a minor resection (p less than 0.001). Patients with gallstones had no significantly longer duration of Crohn's disease prior to the diagnosis of gallstones than patients with no gallstones during the median observation period of 12 years. PMID- 2312045 TI - What's your diagnosis? Part II. PMID- 2312046 TI - A case of gallbladder carcinoma with infiltration into the muscular layer that resulted in relapse and death from metastasis to the liver and lymph nodes. AB - An eighty-six-year old woman was submitted to simple cholecystectomy and choledocholithotomy for acute obstructive cholangitis due to cholecysto choledocholithiasis. At the operation, neither lymphogenic nor hematogenic metastasis was observed. Grossly, a protuberant lesion with an uneven surface and obscure borders was seen spread over the fundus and the body of the resected gallbladder. Histologically, it was a well-differentiated adenocarcinoma with slight invasion to the muscular layer. The patient died of recurrent carcinoma three years and eight months after the operation. At autopsy, multiple metastatic tumors were found in both lobes of the liver, and many lymph node metastases around the hilus of the liver, hepatoduodenal ligament and pancreas were also observed. It is strongly believed that gallbladder carcinomas that infiltrate the muscular layer should be classified as early-stage carcinomas with a fair prognosis, together with mucosal carcinomas. However, on the basis of the present case of relapse following simple cholecystectomy as described above, radical cholecystectomy including a wedge resection of the liver and dissection of the regional lymph nodes would seem necessary even for gallbladder carcinoma with infiltration into the muscular layer. PMID- 2312047 TI - Anemia: monosymptomatic celiac disease. A report of 3 cases. AB - Patients with monosymptomatic celiac disease (CD) can escape diagnosis for a long period. Anemia is a common finding in CD, although anemia as the sole symptom is relatively unknown. We report on three patients who presented with iron deficiency anemia and no other symptom, in whom CD was considered and diagnosed several to many years after the anemia was documented. PMID- 2312048 TI - Agreement among multiple observers on endoscopic diagnosis of esophageal varices before bleeding. AB - The interobserver variation in diagnosis and grading of esophageal varices may be ascribed by characteristics of the observers as well as to the patients. Assessment of this variation therefore requires the contributions of multiple observers and patients. Twenty-eight patients with cirrhosis without previous bleeding or known presence of varices were subjected to upper gastrointestinal endoscopy. Each endoscopy was videotaped and shown to 22 endoscopists. The varices were graded on a scale of 0 to 3 according to size. Each endoscopist diagnosed varices in 8 to 20 patients (mean = 15.9). Overall agreement on the presence (grades 1 to 3) or absence (grade 0) of varices was 70%. The average kappa value was 0.38 (standard deviation = 0.16). Discrimination between varices graded 0 to 1 and varices graded 2 to 3 gave a higher kappa value (p less than 0.01) of 0.52 (standard deviation = 0.17). There was a large variation in kappa values (range = -0.025 to 0.975). No significant correlation was observed between kappa values for the two dichotomies (range = 0.16). The kappa values were not related to the experience of the endoscopist. Considerable variation in the agreement on diagnosis and grading of esophageal varices was found. These results must be taken into account in the assessment of trials of prophylaxis of first time variceal bleeding. PMID- 2312049 TI - Recurrence factors studied by percutaneous transhepatic portography before and after endoscopic sclerotherapy for esophageal varices. AB - High recurrence and rebleeding rates have been reported when endoscopic sclerotherapy has been performed on patients with esophageal varices. We studied the relationship between embolization range and recurrence rate in 26 patients in whom percutaneous transhepatic portography was carried out before and after sclerotherapy. Patients were divided into complete and incomplete embolization groups. The complete embolization group consisted of 16 patients whose esophageal varices had disappeared and in whom embolization of the feeders to the varices had occurred. The incomplete embolization group consisted of 10 patients whose esophageal varices had disappeared, but no embolization had occurred. Recurrence rates within 2 yr after the treatment were compared between complete and incomplete embolization groups. The recurrence rates in the respective groups were 6.7% (1 of 15) and 70.0% (7 of 10), indicating a significant difference between the two groups (p less than 0.05) and indicating that embolization of both esophageal varices and their feeders is essential to lower the recurrence rate after sclerotherapy. PMID- 2312050 TI - Amoxicillin-clavulanic acid therapy of spontaneous bacterial peritonitis: a prospective study of twenty-seven cases in cirrhotic patients. AB - Spontaneous bacterial peritonitis in cirrhosis is a serious complication that demands urgent attention. We report here a prospective study of the treatment of 27 episodes of spontaneous bacterial peritonitis in 22 cirrhotic patients with amoxicillin and clavulanic acid. The infection of ascitic fluid was diagnosed by a positive culture plus an ascitic neutrophil count exceeding 75/microliters, or by an ascitic neutrophil count exceeding 500/microliters. The infection was treated with 1 gm amoxicillin and 0.2 gm clavulanic acid every 6 hr for 14 days. In 17 cases (63%), bacteria were isolated from the ascitic fluid. All the bacteria isolated were sensitive to amoxicillin and clavulanic acid, whereas in five cases they were resistant to amoxicillin alone (Escherichia coli in two cases, Klebsiella pneumoniae in two cases and Bacteroides fragilis in one case). Cure of the infection was achieved in 23 episodes (85%) after 14 days' treatment; 17 patients (63%) were able to leave the hospital. Fourteen of 20 patients (70%) treated for the first episode of infection died within 1 yr: eight from infection, two from gastrointestinal hemorrhage, one from infection and hemorrhage and three from tumors. One patient who had repeated infections underwent liver transplantation and has not had any infectious complications 1.5 yr after surgery. Amoxicillin and clavulanic acid may be an effective first-line therapy for ascitic fluid infection in cirrhosis. Nevertheless, the 1-yr prognosis continues to be grave and the severity of the underlying liver disease remains the most important determinant for survival. PMID- 2312051 TI - Effects of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis. AB - Acute intravenous amino acid infusion or a high-protein diet increases renal plasma flow and the glomerular filtration rate in healthy subjects. Conversely, a low-protein diet reduces renal plasma flow and glomerular filtration rate. The aim of this study was to investigate the effect of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis. Protocol 1: renal plasma flow and glomerular filtration rate were measured before and during intravenous administration of a 10% amino acid solution (0.043 ml/kg/min) to eight compensated cirrhotic patients (group 1), nine nonazotemic cirrhotic patients with ascites (group 2) and seven cirrhotic patients with ascites and functional renal failure (group 3). Amino acid administration induced a significant increase in renal plasma flow and glomerular filtration rate in all groups studied. Renal plasma flow and glomerular filtration rate increased by 16% and 14%, respectively, in group 1; 31% and 22% in group 2 and 25% and 21% in group 3. Protocol 2: Renal plasma flow and glomerular filtration rate were measured in nine cirrhotic patients with ascites after 11 days on a low-protein diet (0.5 gm/kg body weight/day) and also after the patients followed for 11 days a moderately high-protein diet (1.5 gm/kg body weight/day). The moderately high protein diet was associated with a significant increase in renal plasma flow (12%) and glomerular filtration rate (13%) compared with values obtained while the patients followed the low-protein diet. Plasma glucagon levels increased markedly during the intravenous administration of amino acid and the intake of the moderately high-protein diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312052 TI - Rabbit hepatocytes in primary culture: preparation, viability and use in studies of propranolol metabolism. AB - Isolated hepatocyte cultures have become a frequently used model system for investigating drug metabolism. Although rat and hamster hepatocytes are frequently used for this purpose, metabolism in these species differs in many respects from human metabolism. A species with a metabolism more closely resembling that of humans might be more useful. Our in vivo experiments demonstrated that the metabolism of propranolol in the rabbit is more similar to that in humans than in rats or hamsters. We therefore examined the usefulness of rabbit parenchymal liver cells for studies of propranolol metabolism. A detailed method is presented for their preparation and culture, along with data on their viability, structure and protein synthesizing capability. One- or two-day-old hepatocyte cultures were exposed to 10 mumol/L 3H-propranolol from 30 min to 2 hr; metabolites were identified by gas chromatography-mass spectrometry and quantitated by high-performance liquid chromatography. Propranolol metabolism was linear over 1 hr, with 15% of the substrate metabolized during this time. The cytochrome P-450 pathways, which result in ring oxidation and side-chain oxidation, were expressed in a reproducible fashion similar to that found in vivo in humans. The arylhydrocarbon hydroxylase inhibitor alpha-naphthoflavone (100 mumol/L) inhibited side-chain oxidation of propranolol by 90% without affecting ring oxidation. In contrast, chlorpromazine (100 mumol/L) was shown to inhibit ring oxidation of propranolol by 85% without affecting side-chain oxidation. Cimetidine (250 mumol/L) inhibited both pathways by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312053 TI - Formation of the 37-kD protein-acetaldehyde adduct in primary cultured rat hepatocytes exposed to alcohol. AB - We have previously reported that a 37-kD liver protein formed an adduct with acetaldehyde in vivo when rats were fed alcohol chronically. To understand the mechanism of the formation of this protein-acetaldehyde adduct, rat hepatocytes in primary culture were treated with ethanol in vitro for several days. When cultured in hormone-enriched and trace metal-enriched Waymouth's medium, alcohol dehydrogenase activities in hepatocytes decreased only about 30% during 6 days of culture. At the end of the specified time, protein extracts of hepatocytes were immunotransblotted with rabbit immunoglobulin G that recognized acetaldehyde adduct as an epitope. The 37-kD protein-acetaldehyde adduct band could be detected within 3 days in cells that had been treated with alcohol at a steady state concentration as low as 5 mmol/L. Although the maximal intensity was obtained at approximately 10 to 40 mmol/L ethanol, addition of cyanamide (an inhibitor of aldehyde dehydrogenase) further increased the intensity of this protein-acetaldehyde adduct band by more than twofold. A good correlation existed between acetaldehyde concentration in the medium and the intensity of the 37-kD protein-acetaldehyde adduct band. Formation of the 37-kD liver protein acetaldehyde adduct is thus dependent on acetaldehyde, and the 37-kD protein is apparently unusually susceptible to chemical modification by acetaldehyde. PMID- 2312054 TI - Antibodies against the hepatic asialoglycoprotein receptor perfused in situ preferentially attach to periportal liver cells in the rat. AB - Autoantibodies reacting with the galactose-specific hepatic asialoglycoprotein receptor--a liver-specific component expressed on the surfaces of hepatocytes- are often found in patients with chronic active hepatitis of presumed autoimmune origin. As part of an investigation into whether these anti-asialoglycoprotein receptor antibodies might be involved in the development of periportal liver damage in chronic active hepatitis, livers of ether-anesthetized rats were perfused in situ with polyclonal guinea pig anti-rabbit asialoglycoprotein receptor or murine monoclonal anti-human galactose-specific hepatic asialoglycoprotein receptor antibodies in excess at less than 8 degrees C or, as a control, with guinea pig anti-human plasma protein antibodies or normal guinea pig serum. Rapid (1 min) antegrade (by way of portal vein) or retrograde (through hepatic veins by way of vena cava) perfusions were performed in a nonrecirculating (once-through) mode in Ca+(+)-free medium. Blocks of liver tissue were immediately snap-frozen and the distribution of the antibody examined in cryostat sections by using an avidin-biotin immunohistochemical technique. In all of the perfusions with anti-asialoglycoprotein receptor (six antegrade, seven retrograde), the antibodies were found to be prominently and almost exclusively deposited on liver cells in the periportal areas. No deposition of immunoglobulins was detected in livers perfused with the control guinea pig sera. The findings suggest that the asialoglycoprotein receptor is expressed at high density mainly on cells in zone 1 of the hepatic lobule, and this may have implications for the development of periportal liver damage in chronic active hepatitis. PMID- 2312055 TI - Transferrin receptor expression in rat liver: immunohistochemical and biochemical analysis of the effect of age and iron storage. AB - Hepatic transferrin receptors were studied in normal male rats at 1 to 59 wk after weaning, using immunohistochemical and biochemical techniques. The number of transferrin receptors measured and the intensity of the staining in situ decreased rapidly during the first 10 wk of life and more slowly thereafter. Immunohistochemistry further demonstrated changes in the topographical and (sub)cellular localization of the transferrin receptor. In the young rat livers, staining was almost exclusively present on hepatocytes in acinar zone 2 + 3 in a honeycomb to sinusoidal pattern. With aging, a panacinar heterogeneous and mainly sinusoidal staining of hepatocytes was more frequent. Kupffer cell positivity was more obvious as compared with the young rat livers. The observed changes in transferrin receptor expression may partly be explained by age-dependent alterations in DNA synthesis and proliferative potential of the liver cells. A series of rats were iron loaded with carbonyl iron up to 39 wk and "unloaded" by administration of a normal diet during 20 wk. In these animals, serial histochemical studies showed predominantly parenchymal (7 to 14 wk), mixed parenchymal and reticuloendothelial (39 wk) and almost exclusive reticuloendothelial siderosis (59 wk). In the siderotic livers transferrin receptor numbers tended to be lower than in the controls with significant differences after 14 and 39 wk. Immunohistochemistry showed decreased parenchymal but increased reticuloendothelial transferrin receptor expression with iron load. After the period of unloading, parenchymal transferrin receptors were virtually absent despite the negligible siderosis of these cells. In contrast, siderotic reticuloendothelial cells were intensely positive. These findings support down regulation of parenchymal transferrin receptor resulting from iron storage. However, the positivity of siderotic reticuloendothelial cells and the absence of re-emergence of parenchymal receptors in conditions of minimal parenchymal and prominent reticuloendothelial siderosis need further elucidation. PMID- 2312056 TI - The hepatocyte protein synthesis defect induced by galactosamine involves hypomethylation of ribosomal RNA. AB - D-galactosamine produces an early defect in protein synthesis, independent of its effects on RNA synthesis. Here we show that the defect in protein synthesis is inherent in purified ribosomal subunits in vitro. Further, galactosamine treatment is associated with an 85% decrease in methylation of ribosomal RNA, involving all sites (2'-0-ribose and base positions), intact ribosomes from galactosamine-treated animals can be methylated to a greater extent than control ribosomes and in vitro methylation restores their functional capacity. Statistical analyses of these data, along with those with a number of other hepatotoxins, reveal a correlation coefficient of r = 0.95 (p less than 0.003) between protein synthetic capacity and ribosomal RNA methylation, and linear regression accounts for more than 90% of the observed variation. In contrast, no relationship was found between nucleolar RNA methylation and protein synthetic capacity. A relationship of borderline statistical significance was found between messenger RNA methylation and protein synthetic capacity, but it does not appear consistent with results obtained after CCl4 intoxication. These results lend strong support to the notion that methylation status of ribosomal RNA is an important control for protein synthesis in quiescent hepatocytes and that net hypomethylation is a common response to such divergent hepatotoxins as CCl4, ethionine and D-galactosamine. PMID- 2312057 TI - Early involvement of hepatic parenchymal cells in erythrohepatic protoporphyria? An ultrastructural study of patients with and without overt liver disease and the effect of chenodeoxycholic acid treatment. AB - Liver biopsy specimens obtained from two groups of erythrohepatic protoporphyria patients were studied histopathologically and ultrastructurally. Group 1 comprised seven erythrohepatic protoporphyria patients with a normal liver histology; from two patients liver biopsy specimens were available before and after 1 yr of chenodeoxycholic acid treatment. Group 2 consisted of four patients with a history of liver disease and liver histopathology; three patients were observed before and after 1 yr of chenodeoxycholic acid treatment. Liver specimens of nine kidney transplant donors served as controls. Unlike the morphology at the light microscopic level, the ultrastructure of hepatic parenchymal cells was affected in both groups of erythrohepatic protoporphyria patients. In both groups the nuclei, endoplasmic reticulum, lateral plasma membranes and bile canaliculi were altered. Collagen fibers were frequently present. In addition, in group 2 bile thrombi and intracytoplasmic protoporphyrin crystals were observed. After chenodeoxycholic acid administration, the latter feature had diminished. It is concluded that (a) in erythrohepatic protoporphyria ultrastructural changes are present in the hepatic parenchymal cells even in early stages of the disease. Changes in bile canalicular ultrastructure suggest a defective hepatic excretory function, probably caused by the toxic effect of protoporphyrin. (b) Chenodeoxycholic acid administration causes no distinct improvement of the ultrastructure of organelles in the hepatic parenchymal cell or the bile canalicular system but may decrease crystalline protoporphyrin deposition in the liver. PMID- 2312058 TI - Epidemiology of primary biliary cirrhosis in a defined rural population in the northern part of Sweden. AB - The northern part of Sweden is sparsely populated and must be regarded as a rural region. An investigation into the incidence and prevalence of primary biliary cirrhosis was conducted and the course of the disease was followed. In total, 111 patients with primary biliary cirrhosis were identified for the 10-yr period 1973 to 1982 in the northern health region of Sweden. The mean annual incidence amounted to 13.3 per million and the point prevalence was 151 per million, which is the highest reported so far. There was a significantly higher prevalence in the most northern county of Sweden, both with respect to total number of primary biliary cirrhosis patients and symptomatic patients. Asymptomatic patients amounted to 37%. During the study period 25 patients out of the 111 died (23%), 14 as a direct consequence of the liver disease. Three patients died of primary hepatocellular carcinoma, one having an asymptomatic liver disease without cirrhosis. Primary biliary cirrhosis seems to be more common in Sweden, especially in the northern part, than it is elsewhere. A high frequency of extrahepatic symptoms (85%), mainly musculoskeletal, was recorded. These symptoms may lead to the first contact with the health service, rather than signs of liver disease. Thus, an increasing number of patients are diagnosed with asymptomatic liver disease, who must be followed to check for the eventual development of symptoms. PMID- 2312059 TI - The pathology of liver allografts surviving longer than one year. AB - Although prolonged survival after liver transplantation is now common, the condition of allografts after prolonged survival has not been widely discussed. We reviewed 86 biopsy samples from 38 patients. The samples were obtained between 366 and 1,622 days after transplant. Thirteen patients' biopsy samples were normal or showed minor changes. Six patients' samples showed rejection. Four patients, including two with rejection, demonstrated ischemic change. Three patients showed focal fibrosis, polymorphonuclear infiltration and bile duct proliferation simulating biliary obstruction, although biliary stones were found in only one patient. Three patients had acute hepatitis. Seven patients had a pattern of chronic persistent hepatitis; four had chronic active hepatitis. Follow-up biopsy samples were obtained in seven chronic hepatitis patients. Two of the patients with chronic hepatitis patients. Two of the patients with chronic active hepatitis have shown slight progression of the disease. None has progressed to cirrhosis, but neither has the chronic active hepatitis resolved. It is likely that some of these cases represent non-A, non-B hepatitis. Although histological abnormalities are common after successful transplantation, the clinical significance of many of the changes remains to be determined. Only patients with rejection or vascular thromboses required new transplants. PMID- 2312060 TI - The relevance of the order of revascularization in liver grafting. AB - A study was conducted comparing the effects of initial arterialization vs. initial portal revascularization in unstored warm ischemic (for 30 min) livers, livers stored for 4 hr at 0 degrees C in Collins solution and livers rendered warm ischemic for 1 hr before removal and replacement as autografts. All livers that received initial arterialization showed uniform diffuse perfusion, whereas those with initial portal perfusion were patchy and well perfused only in the right lobe. In the experimental animal, initial arterialization using an end-to end method was much easier and required less retraction. The energy charge and ATP levels dropped sharply during brief warm ischemia but returned rapidly to normal on revascularization. Although the decline in energy charge was less in stored livers, the return to normal was slower and incomplete. Plasma levels of AST indicated much greater damage in the stored livers and were lowest in recipients in unstored livers that were arterialized first. After longer warm ischemia, energy charge values declined and only completely returned to 60% of preoperative values within 2 hr of grafting. Despite this, the survival rate of these animals was very poor and only one survived overnight. Seven of the 12 survived the procedure, but in five death occurred within 30 min of full revascularization. In this group, AST levels rose sharply after revascularization to a mean level of 1,000 U.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312062 TI - Hepatic mycobacterial disease and AIDS. PMID- 2312061 TI - Development of colon cancer after liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. AB - Between February 26, 1981, and July 30, 1987, 36 patients underwent orthotopic liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Three of the 36 recipients died within 3 mo because of graft nonfunction or surgical complications. The other 33 (92%) lived for at least 1 yr. Two of the 33 died after 12 and 14 mo, respectively, of recurrent cholangiocarcinoma that was not diagnosed before transplantation. Four other patients died of recurrent liver failure (three cases) or immunoblastic sarcoma (one case) after 14, 21, 36 and 44 mo. Twenty-seven (75%) of the patients are still alive 23 to 81 mo after transplantation. Two patients have been diagnosed as having colorectal cancer 11 and 21 mo respectively, after transplantation, for an overall incidence of 5.6% (2 of 36) and a corrected incidence of 6.5% (2 of 31) if the three early deaths and two later deaths caused by cholangiocarcinomas are excluded. It is not known whether colorectal malignancies were present but undetected at the time of transplantation or whether they developed afterward. It is clear that patients who undergo liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis should have careful follow-up of the colon, including colonoscopy and multiple biopsies of the colorectal mucosa. Whether proctocolectomy should be considered prophylactically after liver transplantation is an unresolved issue. PMID- 2312063 TI - Excision of multiple metastases: better designed studies are needed. PMID- 2312064 TI - Liver dissection in hepatic surgery: ultrasound vs water jet vs suction knife. PMID- 2312065 TI - Hepatocirculatory failure: diverse pathogeneses deserve diverse therapies. PMID- 2312066 TI - Hyperprolinemia and lactatemia in alcoholic liver disease: relationships to abstinence and histological findings. PMID- 2312067 TI - Gallstone pancreatitis: optimal timing. PMID- 2312068 TI - Measurement of hepatic blood flow from ethanol clearance in anesthetized cats. PMID- 2312069 TI - Cirrhosis and its recognition in asymptomatic subjects with aminotransferase elevation. PMID- 2312070 TI - Prognosis in PBC: who should we believe? PMID- 2312071 TI - Britain blazing a well-worn trail. PMID- 2312072 TI - HIV seropositivity in inner-city alcoholics. PMID- 2312073 TI - Perspectives on homeless mentally ill women. PMID- 2312074 TI - The challenge of adaptation: shaping service delivery to meet changing needs. PMID- 2312075 TI - Change in diagnosis at termination of psychiatric consultation. AB - Changes in 358 initial diagnoses made by psychiatric consultants in a medical inpatient setting were examined. Initial diagnoses from five groups--major depression, adjustment disorder with depressed mood, dementia, delirium, and the somatoform disorders--were compared with diagnoses made at termination of consultation. Differences in stability of diagnosis between the groups failed to reach significance (pz = .078). However, a trend was found for diagnoses of major depression to be the least stable; 21.7 percent of initial diagnoses were changed by termination. The results emphasize the provisional nature of initial psychiatric diagnoses in the medical setting and suggest the need for repeated assessment of the patient before beginning potentially hazardous treatment, especially for major depression. PMID- 2312076 TI - Factors contributing to homelessness among the chronically and severely mentally ill. AB - Fifty-three homeless mentally ill patients were studied by two psychiatrists in a treatment setting in which data could be gathered from family members and other third parties as well. All the patients were severely mentally ill when the homelessness immediately preceding the current admission began. For the study group, the disabling functional deficits of major mental illness appeared to be important contributing factors to homelessness. These deficits included disorganized thinking and actions, poor problem-solving skills, inability to mobilize oneself, depression, and paranoia that prevented acceptance of help. Other important factors contributing to homelessness were the lack of a comprehensive and effective system of mental health care, substance abuse combined with severe mental illness, and the tendency for chronically and severely mentally ill persons, especially during their youth, to pursue their life goals in an unrealistic or irrational way. PMID- 2312077 TI - Substance abuse and mental health status of homeless and domiciled low-income users of a medical clinic. AB - Data were collected on indicators of mental health status and substance abuse among 214 homeless and 250 domiciled but impoverished patients who sought care in a community medical clinic in a California beach community. Although both groups had a high prevalence of problems, homeless patients were significantly more likely to have been hospitalized for alcohol or mental problems, to have been arrested because of drinking, and to have experienced delirium tremens. Homeless persons were also more likely to have made a suicide attempt, to have experienced recent psychotic symptoms, and to be dissatisfied with life. The findings suggest that primary medical care settings serving the poor and homeless may present an excellent opportunity for delivering mental health services and that psychiatrists should expand their involvement in such settings. PMID- 2312078 TI - The relationship between admission symptoms and hospital assaults. AB - Assessments at hospital admission of patients' potential for violence often rely on limited information, such as the patient's mental status, because detailed clinical and historical information may not be readily available. This study examined the relationship between symptoms at admission as measured by the Brief Psychiatric Rating Scale and later violence of 127 psychiatric inpatients. Patients who showed higher levels of thinking disturbance, hostile suspiciousness, and agitation-excitement at the time of admission were at greater risk of becoming assaultive during the hospitalization. The findings suggest the usefulness of specific symptom profiles for identifying acute psychiatric patients at risk for violence. PMID- 2312079 TI - Quality of the residential environment in board-and-care homes for mentally and developmentally disabled persons. AB - Data from a multistate survey of board-and-care homes were used to compare the quality of the residential environment in homes for mentally disabled and developmentally disabled persons. Staffing levels, services, quality of the physical structure, rapport between residents and staff, number of residents, staff training, and fire and safety precautions were analyzed. The global quality of the residential environment was found to be appreciably better in homes serving the developmentally disabled. Implications of the findings for public policy are discussed, with specific reference to advocacy strategies used in behalf of developmentally and mentally disabled persons. PMID- 2312080 TI - Do-not-resuscitate decisions on a psychiatric unit. PMID- 2312081 TI - Preferred management styles among psychiatrist-administrators. PMID- 2312082 TI - Continuity and intensity of case management activity in three CMHCs. PMID- 2312083 TI - Knowledge about AIDS among women psychiatric outpatients. PMID- 2312084 TI - Dissociation and abuse among multiple-personality patients, prostitutes, and exotic dancers. PMID- 2312085 TI - Homelessness in Australia. PMID- 2312086 TI - Services for the homeless. PMID- 2312087 TI - Sources of patients' stress. PMID- 2312088 TI - Hiring former patients. PMID- 2312089 TI - A case of noncompliance. PMID- 2312090 TI - Physician outreach gets wide hospital support. PMID- 2312091 TI - Primary care: hospitals begin to target community needs. AB - When financial doom threatened St. John (KS) District Hospital, executives there adopted an unusual strategy. In a bid for survival, St. John is abandoning its acute care service and converting to a primary care-only facility. St. John executives viewed their decision as one way to keep health care services available in a one-hospital town. Other hospital executives are also realizing that expanding primary care services is a smart move. According to experts, in the long run such a move will also help to enhance market share for these hospitals. The need to expand primary health care services has also not escaped the notice of the federal government. Physician payment reform puts more money in the pockets of primary care physicians. "The Health Care Financing Administration is beginning to realize their bang for the buck is in primary care and prevention," says one physician. PMID- 2312092 TI - Groups vie for lucrative managed care accreditation business. AB - The race is on to determine which organization will become the accreditation agency of choice for the managed care industry. At stake is enormous clout at the state and national levels--and a lot of money. Squaring off against the traditional accreditation leader, the Joint Commission on Accreditation of Healthcare Organizations, are: the National Committee for Quality Assurance, the American Association of Preferred Provider Organizations, and the Utilization Review Accreditation Commission. PMID- 2312094 TI - Recruitment firms vital to CEO's job search. PMID- 2312093 TI - Weight-loss programs still fatten profits despite competition. AB - Why are hospitals interested in weight-loss programs? Low start-up costs, combined with a high demand for services, mean almost instant profits in some cases. And in an increasingly competitive market, hospital affiliation seems to be an advantage. But experts say that word of mouth is the best promotion for weight-loss programs, which means that patients must lose weight and keep the pounds off. That's why hospitals have found that patient education is integral to a successful program. PMID- 2312095 TI - Toshiba pursues PACS research into the 1990s. PMID- 2312096 TI - Elderly face new issues with outpatient care. PMID- 2312097 TI - Efficacy of care new focus for precert programs. PMID- 2312098 TI - State regulators getting tougher on HMOs. PMID- 2312099 TI - Will clinical care guidelines cut costs in MN? PMID- 2312100 TI - Ambulatory surgery gets high marks from the elderly. PMID- 2312101 TI - Vendor shakeups may rock hospital systems. PMID- 2312102 TI - Graduate programs cater to working CEOs. PMID- 2312103 TI - Health care in the '90s: not more of the same. PMID- 2312104 TI - The foveolar cell component of gastric cancer. AB - M1, a mucin antigen, and cathepsin E, an aspartic proteinase, are both expressed in normal gastric superficial-foveolar epithelial cells. In this study, we determined by immunohistochemical staining the prevalence of these antigens in 316 gastric cancers representative of the main histologic types and stages of the disease. M1 was expressed in 201 cases (64%) and cathepsin E was expressed in 235 cases (75%) of the 313 cases investigated. Both antigens were expressed more commonly in diffuse and mixed cancers than in glandular tumors. M1 was found in 64 of 83 (77%) diffuse cancers and in 48 of 59 (81%) mixed cancers, but in only 74 of 146 (51%) glandular cancers. For cathepsin E, the prevalence was 93% in diffuse cancer, 81% in mixed cancer, and 71% in the 143 glandular cancers examined. Among 25 mucoid tumors, 15 (60%) expressed M1 but only eight (32%) expressed cathepsin E. Overall, 262 (84%) of the tumors expressed at least one of these antigens and of these, 173 (66%) expressed both antigens. No significant difference in the prevalence of M1 or cathepsin E was found between early and advanced cancer or between metastatic and nonmetastatic cancer. The two markers differed in their intracellular localization. In superficial-foveolar cells, M1 immunostaining was concentrated in secretory granules, Golgi complex, and luminal mucous, whereas cathepsin E was found in the endoplasmic reticulum. Moreover, cathepsin E, but not M1, was found in the enterocytes of duodenal villi and, occasionally, in mucopeptic cells. Parallel histochemical and ultrastructural investigations confirmed the occurrence in gastric cancer of foveolar-type cells, manifested by periodic acid-Schiff- and/or alcian blue-reactive mucous granules having a punctate substructure. We conclude that superficial-foveolar cell differentiation is common in gastric cancer and is a major component of this type of tumor. However, pure foveolar cell differentiation is rare. Rather, most gastric cancers consist of cells exhibiting features of foveolar, intestinal, and mucopeptic cell lines. PMID- 2312105 TI - Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma. AB - Epidermal growth factor (EGF) receptors were examined immunohistochemically in 64 adrenocortical carcinomas obtained at autopsy, and in 23 adrenocortical adenomas and seven pheochromocytomas obtained during surgery. In the nonneoplastic adrenal gland, EGF receptors were scattered to the zona glomerulosa, zona fasciculata, and zona reticularis. Adrenocortical carcinomas (63 of 64), more than adrenocortical adenomas (10 of 23) or pheochromocytomas (four of seven), stained positively for EGF receptors (P less than .01). The immunoreactivity was limited to the cytoplasm, cell membrane, and chromatin. When the antibody was immunoabsorbed with an excess of immunogen peptide, there was no evidence of immunostaining. The adrenocortical carcinomas could be classified into 16 cases of the well-differentiated type, 33 cases of the moderately differentiated type, and 15 cases of the poorly differentiated type. There was no relationship between histologic grading and staining intensity of the EGF receptors. On the other hand, more than 80% of the cases of adrenocortical carcinomas revealed a moderate to high intensity for EGF receptors. In 62 of the 64 patients, there was already metastases to other organs. We conclude that the expression of EGF receptors is associated with tumor growth and/or metastatic potential in adrenocortical carcinoma. PMID- 2312106 TI - Distant metastases in differentiated thyroid carcinomas: a clinical and pathologic study. AB - Of 514 patients with differentiated thyroid carcinoma treated between 1970 and 1987, 34 (6.6%) had distant metastases. Twelve patients died of their distant metastases; eight of these patients died within 5 years from the time of initial diagnosis. Death from cancer was most frequent in the seventh decade. The metastases were most often found in the lungs and bones. In the fatal group, pleural, brain, and pericardial metastases were noted. Local recurrences were found only in 24% of these 34 patients. Histologic types of primary thyroid tumors and metastatic tumors were reexamined and classified using our criteria, which were mainly based on the World Health Organization nomenclature and currently obtained pathologic observations of thyroid tumors. In 31 thyroid tumors, the surgical specimens were available for review. Twenty-four tumors were papillary and seven were follicular. Of the 24 papillary carcinomas, nine were follicular, eight were well-differentiated, and seven were trabecular. On the other hand, the seven follicular carcinomas consisted of four well differentiated, two solid, and one oxyphilic. The majority of the thyroid tumors showed an extrathyroidal extension; however, two were intrathyroidal carcinomas and two were encapsulated carcinomas, larger than 5 cm in diameter. Distant metastases were confirmed morphologically in 18 patients (11 by surgical or biopsy material, five by autopsy, and two by cytology). The histologic types of metastatic tumors were consistent with those of primary thyroid tumors. Diagnostic 131I uptake was examined in 32 patients and absorption of diagnostic 131I in metastatic tumors was demonstrated in 21 patients. The 10-year survival rate of patients with 131I accumulating metastases (70%) was significantly better than that of patients with metastases lacking such uptake (40%). Immunoreactivity for thyroglobulin in metastatic tumors was correlated with the 131I absorption. This finding indicated that immunostaining of thyroglobulin in metastatic tumors might be useful in the prediction of the effectiveness of 131I therapy. PMID- 2312107 TI - Dissecting aneurysm: a clinicopathologic and histopathologic study of 111 autopsied cases. AB - One hundred eleven autopsy cases of dissecting aneurysm were collected from western Japan. The ratio of males to females was 3:2 and the sixth and seventh decades of life were most frequently affected. All 11 cases of Marfan's syndrome were in patients under 40 years of age. DeBakey's type III dissections showed a male predilection and more severe atherosclerosis than in control cases. Many patients with types I and II dissections died of hemorrhage in the acute phase, while many patients with type III dissection died in the subacute or chronic phase, and half of the patients died of diseases other than hemorrhage. Hypertension was recognized in 73.7% of the 95 cases which showed no other obvious risk factors. Histologic examinations suggested that cystic medial necrosis was related to the pathogenesis of the disease in Marfan's syndrome, but was not so apparent in non-Marfan's syndrome. Laminar medial necrosis was found in many cases, but was considered to be a secondary ischemic change following dissection, as supported by other investigators. There were only a few cases in which dissection seemed to be directly caused by atherosclerosis. PMID- 2312109 TI - Gastric adenocarcinoma: prognostic significance of several pathologic parameters and histologic classifications. AB - Considerable controversy exists about the value of histologic classifications of gastric adenocarcinoma in the prediction of patient survival. Histologic sections of 75 consecutive gastrectomies were used to compare Lauren and Ming classifications with emphasis on clinical stage, size, location of tumor, desmoplasia, inflammatory reaction, and 5-year survival. Both classifications generally correlated and, when combined, proved helpful in defining certain cases. At surgery, about one third of the total cases of intestinal (INT, Lauren) and expanding (ET, Ming) were in early stages, whereas almost all the diffuse (DT, Lauren) and infiltrative (INF, Ming) types were in late stages. When the Lauren classification was applied to preoperative endoscopic biopsies, a 72% diagnostic correlation with the surgical specimens was found. Followup revealed no survivors of the DT and INF and 12 and 11 survivors of INT and ET, respectively, regardless of stage. Inflammatory response was associated with good prognosis. Desmoplasia and size had no prognostic significance. Tumors of the cardia had worse prognoses than those in the body or antrum. Both Lauren and Ming classifications, and especially the degree of inflammation, were significant in predicting survival. Lauren INT and Ming ET should be declared only when they are the sole or predominant features. PMID- 2312108 TI - Expression of histocompatibility antigens and characterization of the lymphocyte infiltrate in hyperplastic polyps of the large bowel. AB - HLA-DR expression, lymphocyte subsets, and the distribution of proliferating cells were studied in hyperplastic polyps from the colorectum. The density of T cells (CD5+) (mean of cells/mm2 of tissue +/- SEM) was higher in the lamina propria of hyperplastic polyps (64.2 +/- 4.2) than in normal colonic mucosa (36.7 +/- 2.6, P less than .001). The CD4/CD8 ratio was higher in hyperplastic polyps (6.3 +/- 0.9, P less than .0001) and in colonic adenomas (5.9 +/- 0.9, P less than .001) compared with normal mucosa (2.3 +/- 0.2). Lymphocytes of the lamina propria were never Ki-67 positive either in normal mucosa or in hyperplastic polyps or adenomas. The epithelial layer of hyperplastic polyps and of normal mucosa did not express the HLA-DR antigen, whereas pericryptal fibroblasts and most of the leukocytes of the lamina propria were strongly positive for this antigen. In the epithelial layer proliferating cells were localized exclusively in the lower part of epithelial crypts, as was the case in normal mucosa, whereas in adenomas Ki-67-positive cells were present throughout the entire height of the mucosa. Thus, in hyperplastic polyps lymphocytes are increased in the lamina propria, with a predominance of the CD4 subset in close contact with HLA-DR positive pericryptal fibroblasts. PMID- 2312110 TI - Infiltrating cribriform carcinoma of the breast: a distinctive clinicopathologic entity. AB - All cases of primary breast carcinoma seen at the George Washington University Medical Center between 1971 and 1975 and between 1981 and 1986 were reviewed, and examples of pure and mixed infiltrating cribriform carcinoma (ICC) were identified. The relative frequency of ICC did not change significantly from the earlier to the later study period. As previously reported by Page et al, there was a tendency for ICC to be associated with foci of tubular carcinoma and of intraductal carcinoma (often but not always of cribriform type). Pure ICC (defined as showing no other infiltrating carcinoma type), predominant ICC with lesser amounts of infiltrating carcinoma of any other type and any quantitative combination of ICC and tubular carcinoma metastasized to axillary lymph nodes frequently, but almost never to more than three nodes, in contradistinction to tumors composed of infiltrating duct carcinoma (IDC) not otherwise specified and less than 50% ICC, and a control group of IDC, which significantly more often involved four or more nodes. ICC cases were estrogen-receptor-positive in 100% and progesterone-receptor-positive in 69% of the cases. Five-year survival rates for eligible cases were 100% for pure and greater than or equal to 50% ICC, 88% for less than 50% ICC, and 78.3% for the IDC controls. ICC is a histologically and clinically distinctive type of mammary carcinoma that should be separated from IDC and other tumor types. PMID- 2312111 TI - Embryonal remnants in inguinal hernia sacs. AB - Inguinal herniorrhaphy is the most common general surgical procedure performed on the neonate or young pediatric patient. The vas deferens and epididymis are vulnerable to damage, including transection during inguinal exploration or hernia repair. Occasionally the surgical pathologist encounters glandular or tubular epithelial-lined structures in hernia sac tissue. Significant medicolegal implications arise when embryonal remnants are mistakenly identified as true vas deferens or epididymis. This study evaluates the incidence and morphology of these embryonal remnants in hernia sacs from patients of The Children's Hospital, Denver, CO. Embryonal remnants were found in 1.5% of 599 hernia sacs from 427 consecutively operated males aged 37 weeks gestation to 19 years. True vas deferens and epididymis were each identified once for an incidence of 0.33%. The remnants resemble either vas deferens or epididymis. The average remnant diameter is 0.17 mm, and did not change significantly with age. Remnants are surrounded by varying amounts of condensed mesenchyme, trichrome-negative for muscle. The testes and vasa differentia from 32 autopsy cases, ranging in age from 26 weeks gestation to 7 years of age, were used to evaluate normal development and morphology of the vas deferens, epididymis and embryonal remnants. The vas deferens is well developed by 26 weeks gestation. The surrounding smooth-muscle coat does not stain with trichrome until 32 weeks gestation. The vas deferens increases in diameter in a linear fashion during gestation, and continues to increase in diameter in the postnatal period. The vas deferens at 4 months of age is 1.2 to 1.4 mm in diameter; this is also the age of highest incidence of bilateral herniorrhaphies and presence of remnants. PMID- 2312112 TI - Sampling of prostatic tissue. PMID- 2312113 TI - Cutaneous herpes simplex infections. AB - OBJECTIVE: To review the clinical features and natural history of cutaneous herpes simplex infections associated with genital herpes. DESIGN: A retrospective case note study of all patients presenting to James Pringle House with this condition between 1983-1987. SUBJECTS: 123 patients were identified. RESULTS: The commonest sites involved were the buttocks 64/186 (34%), suprapubic area 28/186 (15%) and thigh 14/186 (7.5%). Thirty five of the 123 (28%) patients had more than one anatomical site involved. Genital and extragenital recurrences occurred with similar frequency. DISCUSSION: Extragenital cutaneous herpes simplex is not uncommon. Lesions may occur virtually anywhere on the body. HSV should always be considered in the differential diagnosis of vesiculating skin lesions. PMID- 2312114 TI - Gastrointestinal obstruction associated with Chlamydia trachomatis. AB - A patient is reported in whom adhesive obstruction of the small bowel was due to generalised peritonitis caused by Chlamydia trachomatis. It is concluded that any sexually active female with unexplained peritonitis or adhesive obstruction of the small bowel should be screened for chlamydial infection. PMID- 2312115 TI - Increase of infectious syphilis among heterosexuals in Amsterdam: its relationship to drug use and prostitution. AB - Since 1986, an increase in heterosexually acquired syphilis cases has been seen in Amsterdam. The proportion of syphilis patients who reported using hard drugs, increased from 7% in 1985 to 23% in 1988, which was mainly due to increased numbers of addicted prostitute women with syphilis. PMID- 2312116 TI - Male genital ulcerations in Paris (France): absence of correlation between clinical aspect and microbiological data. PMID- 2312117 TI - Preliminary evaluation of cold coagulation as a treatment for cervical intraepithelial neoplasia in a department of genitourinary medicine. PMID- 2312118 TI - Sexual transmission of Gardnerella vaginalis. PMID- 2312119 TI - Medical audit in the UK. PMID- 2312120 TI - Genital herpes diagnosed by cervical cytology. PMID- 2312121 TI - Labial adhesions after genital herpes infection--authors reply. PMID- 2312122 TI - Holey prepuce following genital ulceration. PMID- 2312123 TI - Anti-sperm antibodies in homosexual men: prevalence and correlation with sexual behaviour. AB - The sera of 60 homosexual males were examined for the presence of antibodies to sperm using an indirect immunobead test (IBT). Six of 60 (10%) had antibodies of IgG isotype; in addition two of the six had antibodies of IgA isotype. The presence of antibodies was associated with the practice of unprotected receptive anal intercourse in the previous six months. Antibodies were not found in homosexual men who were celibate, or who practised only oral intercourse during the same period. There was no correlation between the presence of anti-sperm antibodies and antibodies to human immunodeficiency virus (HIV), or numbers of T lymphocytes. These preliminary results lend support to the hypothesis that antigen presentation in the lower gut may be a source of sensitisation against sperm. The possibility that anti-sperm antibodies may be a marker of receptive anal intercourse merits further investigation. PMID- 2312124 TI - Alpha-1-antitrypsin (protease inhibitor) phenotypes and longevity. AB - We have tested the hypothesis that the protease inhibitor phenotypes MZ and MS are disadvantageous and reduce survival by comparing the prevalence of these phenotypes in a group of 707 very old people (hospital patients) with the prevalences reported in younger populations of blood donors. The MS and MZ phenotypes appear to be no less common among those who have survived to old age, but a highly significant difference was found in the occurrence of the M subtypes. The M1 type was more common in the elderly, and the M heterozygotes were less common than would be predicted from the reported incidence in younger groups and from the Hardy-Weinberg equilibrium. This discrepancy appeared to be smaller in subjects of Mediterranean origin than in those of British or Irish genetic background. PMID- 2312125 TI - Genetic-epidemiologic study of haemophilia A and B in Hungary. AB - All known surviving haemophiliacs A and B and their relatives were reexamined by laboratory and clinical methods and evaluated by a genetic-epidemiologic approach in 4 north-western countries of Hungary. The prevalence of haemophilia A and B patients born in the fifties was 2.73 and 0.25 per 10,000 persons, respectively. The reproductive fitness was found to be 0.3 in haemophilia A, and 0.8 in haemophilia B patients. The mutation rates calculated by the indirect method were 6.3 x 10(-5) for haemophilia A and 0.2 x 10(-5) for haemophilia B. PMID- 2312126 TI - GC subtyping and HIV infection in a Spanish population: no evidence of an association between GC subtypes and AIDS. AB - Group-specific component (GC) subtyping was performed by isoelectric focusing in 318 Spanish drug users at risk for infection or infected by HIV (85 HIV seronegatives, 111 HIV seropositives without symptoms, 89 seropositives with symptoms, 33 AIDS patients) and 187 healthy individuals. There was no significant association between GC subtypes and susceptibility to HIV infection and/or progression to AIDS. PMID- 2312127 TI - Formal and population genetics of F13A and FUCA1 polymorphisms in northern Portugal. AB - Subunit A of coagulation factor XIII (F13A) and alpha-L-fucosidase (FUCA1) polymorphisms were studied in unrelated healthy blood donors from northern Portugal. The gene frequencies found were: F13A*2 = 0.241 and FUCA1*2 = 0.308. Segregation analysis in mother/child pairs and nuclear families confirmed the previously described modes of inheritance for F13A and FUCA1, and no evidence for silent genes was found. PMID- 2312128 TI - Genetic variation of alpha-2-HS-glycoprotein in the Kyushu district of Japan: description of three new rare variants. AB - The genetic polymorphism of alpha 2-HS-glycoprotein (AHSG) was studied in the Kyushu district of Japan using polyacrylamide gel isoelectric focusing, followed by immunoblotting. Three new rare variants were observed and designated AHSG*16, AHSG*17 and AHSG*18, tentatively. The frequencies of the polymorphic genes AHSG*1 and AHSG*2 were similar to those in other areas of Japan. PMID- 2312129 TI - A new complement factor B variant (BF S075) in Japanese. AB - A new slow-moving variant of the complement factor B, named BF S075, was found in a Japanese patient with cerebral thrombosis and urticaria. The variant was inherited in a codominant manner. The protein concentration and functional hemolytic activity of the complement factor B in the patient's serum were within normal limits. The BF S075 is the fourth rare BF variant found in the Japanese population. PMID- 2312130 TI - Monoclonal antibodies define the characteristics and cellular distribution of an Ia-associated protein. AB - In a recent report we described the identification of physical associations between Major Histocompatibility Complex (MHC) Class II (Ia) antigens and other structures of Mr 67,000, which were significantly enhanced following brief T-B cell co-culture (1). To further investigate this 67K Ia-associated product, monoclonal antibodies (MAb) were produced against isolated 67K material and their reactivity examined. Cell surface binding by these MAb was detected only after perturbation of the membrane by cellular adherence or following aldehyde fixation, which indicates that the determinant recognized by these mAb is retained in the plasma membrane in a covert fashion. All lymphoid cells tested showed reactivity with the MAb as determined by immunofluorescence and by ELISA, but no binding was detected on bone marrow or peritoneal macrophages. Expression of the antigen reactive with these antibodies followed a similar pattern with established murine cell lines, with T and B cell lines and a pre-B cell line showing reactivity, while no antigen was detected on macrophage-like and fibroblast cell lines. The intensity of antigen expression by normal lymphoid cells was ordered: thymocytes greater than splenic T cells greater than or equal to bone marrow lymphocytes greater than splenic B cells. No correlation was observed between expression of Ia antigens by non-lymphoid cells and expression of the 67K molecule. These observations suggest that this antigen is primarily a marker of lymphoid cells, with the highest expression on cells of the T lymphocyte lineage. Finally, inhibition of antigen-specific, MHC-restricted T cell activation by the MAb directed against the 67K structure suggests an important functional role for this interesting molecule originally identified by its physical association with Ia following T-B cell interactions. PMID- 2312131 TI - Mouse-human chimeric monoclonal antibody to carcinoembryonic antigen (CEA): in vitro and in vivo activities. AB - Mouse-human chimeric antibody specific for human carcinoembryonic antigen (CEA) was produced by recombinant DNA techniques. The genes of the mouse variable regions of heavy and light chains were cloned from the mouse hybridoma, 2.7.1G.10., which secreted anti human CEA antibody (IgG1, kappa), and were joined with human gamma 1 and kappa constant genes. The affinity of the resultant chimeric antibody to its relevant antigen was the same as that of the parental mouse monoclonal antibody when analysed by Scatchard plot analysis. The chimeric antibody showed a potent antibody dependent cell-mediated cytotoxicity (ADCC) activity with human peripheral blood mononuclear cells against CEA-positive human adenocarcinoma cells. In vivo imaging analysis revealed that the present chimeric antibody was specifically localized on the tumor site. These results indicate that our mouse-human chimeric antibody is a promising reagent for the diagnosis and therapy of CEA-positive human cancers. PMID- 2312132 TI - Production and characterization of a monoclonal antibody against neopterin. AB - We have produced and characterized the first monoclonal antibody against neopterin (D-erythro-6-(1,2,3,-trihydroxypropyl)pterin). The antibody specifically recognizes neopterin in a modified RIA. The binding capacity in this assay is 34%, the sensitivity limit of inhibition is 0.9 nmol/l. Cross-reactivity exists with monapterin (L-threo(1,2,3,trihydroxypropyl)pterin) in 30%, with other pteridines cross-reactivity has been found in less than 5%. PMID- 2312133 TI - Parameters involved in the in vitro immunization of tonsilar lymphocytes: effects of rIL-2 and muramyl dipeptide. AB - A method for the in vitro immunization of human tonsilar lymphocytes is described. This method allows for the sensitization of B-cells against various antigens under serum-free medium conditions. The medium is supplemented with defined concentrations of antigen, rIL-2 and muramyl dipeptide to boost the immune responses. This method may prove useful for the generation of antigen reactive B-cells for use in human monoclonal antibody production and the study of the effects of other lymphokines on the in vitro immune response. PMID- 2312135 TI - Special issue on circulatory support systems. PMID- 2312134 TI - Circulatory support systems entering the 1990's. PMID- 2312136 TI - Theoretical and experimental analysis of right ventricular bypass and univentricular circulatory support. AB - In this paper we examine the dynamic coupling between cardiac pump events and vascular arterial-venous factors that regulate the rate of blood flow around the circulation. A series of experiments were designed to test the feasibility of maintaining vascular and pulmonary function in the absence of the right heart and to characterize the physiologic and hemodynamic consequence of such an exclusion. Theoretical analysis of the cardiovascular system (excluding neuro-humoral factors) using both lumped time invariant and distributed compartmental mathematical equivalent representations, demonstrated that a change in cardiac output (Q) has an inverse-linear effect on venous and direct-linear effect on arterial pressure. A single blood-pump, in a form of a mechanical substitute or the biologic left-heart, alone can support the circulation. Cardiac output reserve is limited (50 percent of normal) because of the rapidly diminishing pulmonary venous-pressure as outflow is increased, irrespective of the pump's specific characteristics. Experiments in animals combined with mock-circulatory studies and computer modeling confirm that near normal flow can be sustained by increasing the stressed blood volume or reducing selectively the systemic venous compliance (i.e., inflatable pressure suit, venous constriction, intra-abdominal compression maneuvers, etc.). The right heart is not essential for normal pulmonary circulation but serves to maintain low systemic venous pressure and relatively high left-heart flow reserve. Purely mechanical properties of the vascular system determine the control and stability of the circulation. PMID- 2312137 TI - Design and control of the atrio-aortic left ventricular assist device based on O2 consumption. AB - The left ventricular assist device (LVAD) is used in parallel with the left ventricle to temporarily assist patients with diminished cardiac function for the purpose of minimizing heart workload and to maintain systemic arterial perfusion. The proper adjustment and timing of the pneumatic LVAD is important such that this goal is achieved. Previous investigations into the left ventricular assist device are inconclusive regarding the optimal utilization of this device. This paper documents a protocol for optimal timing of the LVAD. Timing is studied using a closed-loop analog model of the heart, vascular system, and the LVAD. The model is tested for basic representation of the physiological system. The LVAD is incorporated into the model to discover its interaction with cardiac preload and afterload. Heart workload is computed via the pressure-volume-area method. The normal and impaired heart are modeled, in each case the pump control variables are adjusted. A protocol for adjustment of the LVAD is proposed based on reduced heart oxygen consumption. It was found that the pump should begin ejection immediately after the close of the aortic valve and that the pump filling pressure should be set to a value which produces maximum filling of the pump. Although aortic pressure and flow could be improved at pump rates above the heart rate, oxygen utilization of the heart could only be minimized for synchronous pumping. The adjustment of the pump ejection pressure is a tradeoff between d/dt (LVO2) and stroke volume and mean arterial pressure. The LVAD should be designed to minimize inflow and outflow resistance and to maximize pump compliance. The process of weaning the patient from the LVAD is considered. The overall results provide quantitative guidance for the use of the AA-LVAD. PMID- 2312139 TI - Development of an implantable motor-driven assist pump system. AB - A motor-driven artificial pump and its transcutaneous energy transmission (TET) system have been developed. The artificial pump consists of a high-speed dc brushless motor driving a ball screw and magnetic coupling mechanism between the blood pump and ball screw. The ball screw transfers high-speed rotary motion into low-speed rectilinear motion by a single component. Magnetic coupling enables active blood filling without applying an excess negative pressure to the pump. The transcutaneous transformer is formed from a pair of concave/convex ferrite cores. This design minimizes lateral motion of the external core. Information on motor voltage is transmitted through the skin by infrared pulses. The motor voltage is regulated by controlling the duty ratio of the square pulse supplied to the primary coil. Pump flow of 5.6 l/min was obtained with a mean outlet pressure of 100 mmHg at a drive rate of 100 bpm under preload of 15 mmHg. The performance of synchronous pumping has been very satisfactory. Continuous pumping was maintained by the backup battery in the case of interruption of TET. 24 W were transmitted by TET system with 78 percent of efficiency. Temperature rise of the internal core was 0.2 C. The developed system is promising as an implantable assist pump system. PMID- 2312138 TI - Permanent circulatory support systems at the Pennsylvania State University. AB - Permanent circulatory support systems are required for patients in whom myocardial damage is irreversible and cardiac transplantation is not possible. Two systems are described which provide long term circulatory support: the left ventricular assist system and the total artificial heart. These systems are based on the design of a pusher plate actuated blood pump, driven by a small brushless dc electric motor and rollerscrew driver. An implantable motor controller maintains suitable physiologic flow rates for both systems and controls left right balance in the total artificial heart. Other parts of the system include an intra-thoracic compliance chamber, transcutaneous energy and data transmission system, and internal and external batteries. PMID- 2312140 TI - A multiple disk centrifugal pump as a blood flow device. AB - A multiple disk, shear force, valveless centrifugal pump was studied to determine its suitability as a blood flow device. A pulsatile version of the Tesla viscous flow turbine was designed by modifying the original steady flow pump concept to produce physiological pressures and flows with the aid of controlling circuitry. Pressures and flows from this pump were compared to a Harvard Apparatus pulsatile piston pump. Both pumps were connected to an artificial circulatory system. Frequency and systolic duration were varied over a range of physiological conditions for both pumps. The results indicated that the Tesla pump, operating in a pulsatile mode, is capable of producing physiologic pressures and flows similar to the Harvard pump and other pulsatile blood pumps. PMID- 2312141 TI - Left atrial pressure controller design for an artificial heart. AB - This paper describes the application of a dynamic compensator technique to the left atrial controller design for use with a portable artificial heart drive system. The compensator is designed using a method in the field of multivariable control. This controller design is based on the physical models of the actuator and blood pump system. The analysis shows that there exists a minimal compensator with a dimension of one. The computer simulation demonstrates the acceptable, robust control performance of the left atrial pressure for a relatively small parameter variation of the vascular system model when all the poles of the closed loop system are assigned to appropriate values. PMID- 2312142 TI - Cardiac energy considerations during intraaortic balloon pumping. AB - Cardiac oxygen availability and oxygen consumption were used in a theoretical study as indexes of myocardial energy supply and utilization, respectively. A detailed computer simulation of the closed-loop canine cardiovascular system was utilized to study the dependence of these indexes on timing of the intraaortic balloon pump. Oxygen availability exhibited higher sensitivity to balloon timing than oxygen utilization. While maximum augmentation of oxygen availability was 58 percent, oxygen consumption could be reduced by only 13 percent. Animal experiments were initiated to validate the theoretical results. The results of both the animal experiments and the computer simulation suggested that neither balloon timing which maximizes oxygen availability nor timing which minimizes oxygen consumption correlates with timing which minimizes aortic end diastolic pressure. Thus, end diastolic pressure, presently used as a determinant of proper timing in patients undergoing cardiac assistance, was found to be a poor index of ventricular energy consumption. A performance index comprised of clinically available variables, was formulated to reflect myocardial energy balance. In this performance index, mean diastolic pressure was used to represent energy availability and peak systolic pressure was used as an index of oxygen consumption. Their relationship to oxygen balance and their dependence on timing were studied using the computer simulation of the canine cardiovascular system and animal experiments. Theoretical and experimental results suggest that such an index is capable of representing O2 balance and can be used to control phasing of the device. PMID- 2312143 TI - A closed-loop control scheme for intraaortic balloon pumping. AB - The beneficial hemodynamic effects of IABP are critically dependent on balloon timing relative to the diastolic phase of the cardiac cycle. A microprocessor based controller has been developed to implement real-time automation of IABP using P-R intervals to regulate balloon deflation and systolic time intervals to trigger balloon inflation in a semi-automatic fashion. Experiments were performed on anesthetized open-chest dogs. Simultaneous measurement of aortic pressure and flow, coronary flow, and left ventricular pressure were recorded. Muscle segment lengths in normal and ischemic border zones were also measured from implanted pairs of endocardial ultrasonic dimension gages. P-waves were obtained from atrial cardiograms, and heart sounds were detected using a special filtering circuit. Both signals were input together with ECG to automate IABP timing. Systolic time intervals were calculated in real-time. IABP efficacy was assessed from changes in aortic flow, coronary flow, tension time index, end diastolic pressure, and the endocardial viability ratio. Comparisons were made between automated and manual timing set by a certified technician. Results indicate that automated timing yielded equivalent hemodynamic enhancement with greater ease of adjustment. A closed-loop control scheme is proposed which allows complete automatic device operation and the capability to rapidly achieve the optimum of any directly measurable hemodynamic variable. PMID- 2312144 TI - The Hemopump--a new cardiac prothesis device. AB - A unique cardiac prothesis device is currently undergoing clinical trials. Called the Hemopump, this device is a radical new design of a temporary left ventricular assist blood pump. It uses a miniature (7 mm diameter) axial flow pump placed transvalvular across the aortic valve which pumps blood from the left ventricle to the aorta. Mechanical power from an external motor is transmitted percutaneously to the pump by a flexible cable contained within a catheter-like sheath. This arrangement allows the pump to be placed through a femoral artery cutdown without requiring major surgery. Development of the Hemopump concept presented significant challenges in pump hydraulic design, bearing, and seal design, as well as materials selection and miniature parts fabrication. Clinical trial results thus far indicate these challenges have been well met and that the Hemopump has the potential to become a widely used safe and effective clinical device. PMID- 2312145 TI - System for mechanical measurements during cardiopulmonary resuscitation in humans. AB - Effective study of CPR requires measurement of the mechanical properties of the human chest and the resultant vascular pressures. A computer-based mobile data acquisition system was designed and built for this purpose. During manual CPR a short cylindrical module was placed between the rescuer's hands and the patient's chest. This module, which was attached to an easily manipulated position-sensing arm, measured force and acceleration at the sternum. Three-dimensional position and orientation of the module were measured, as well as the component of the applied force which was perpendicular to the sternum. The central venous and aortic pressures were measured by high fidelity pressure transducers. All transducer signals were recorded by digital computer. Real-time feedback of sternal force and displacement, and vascular pressures was provided to the rescue team via chart recordings. An audible signal was produced as an aid in maintaining desired compression rate and duration. The system's mobility permitted rapid implementation at any hospital location. In conclusion, this system was capable of measuring, recording, and displaying multiple physical quantities during manual CPR in humans. PMID- 2312146 TI - Identification of dynamic mechanical parameters of the human chest during manual cardiopulmonary resuscitation. AB - Survival from cardiac arrest is dependent on timely cardiopulmonary resuscitation (CPR). Since CPR is often unsuccessful, the outcome may be improved by a better understanding of the relationship between force applied to the sternum and the resulting hemodynamic effects. The first step in this complex chain of interactions is the mechanical response of the chest wall to cyclical compression. We formulated a dynamic mechanical model of the chest response and developed a method of identification of the model parameters based on force, displacement, and acceleration data acquired during cyclical compressions. The elasticity, damping, and equivalent mass of the human chest were estimated with a constrained nonlinear least-mean-square identification technique. The method was validated on data acquired from a test apparatus built for this purpose. The model fit was measured with the normalized chi-square statistic on residuals obtained between recorded force and force predicted by the model. In the analysis of one human chest, the elasticity was found to be nonlinear and statistically different during compression and release. A considerable amount of damping was found, with no significant difference between compression and release. The equivalent mass was too small to be determined accurately. This method can be used to obtain the dynamic mechanical parameters of the human chest and may lead to a better understanding of CPR. PMID- 2312147 TI - [Commentary on the press announcement "The first German preparation against HIV"]. PMID- 2312148 TI - [Functional and morphological characterization of alveolar macrophages from patients with pulmonary sarcoidosis]. AB - Bronchoalveolar lavage was performed in 28 patients with pulmonary sarcoidosis. Enzyme cytochemical staining with the tartrate-resistant acid phosphatase revealed a significantly increased portion of sarcoidosis macrophages showing a monocyte-like phenotype. Immunocytochemical staining with the proliferation associated monoclonal antibody Ki-67 showed an increase of proliferating monocyte/macrophages related to disease activity in sarcoidosis. A functional activation of alveolar macrophages in sarcoidosis is indicated by spontaneous interleukin-1 secretion and increased release of oxygen free radical in sarcoidosis alveolar macrophages. PMID- 2312149 TI - Anti-CD3 antibody-induced expression of both p55 and p75 chains of the high affinity interleukin-2 receptor on human T lymphocytes is inhibited by cyclosporin A. AB - The inhibitory effect of cyclosporin (CsA) was investigated on human lymphocytes stimulated by anti-T-cell antibodies (anti-CD3 and -CD2) or mitogenic lectins. Whereas inhibition of cell proliferation (50%) occurred at 10 ng/ml CsA after cell activation via CD3 or CD2, higher CsA concentrations (300 ng/ml) were necessary to inhibit lectin-mediated cell activation (PHA, Con A). Exogenous recombinant interleukin-2 (rIL-2) partially reversed the inhibitory effect on antibody-stimulated cells only; however, at higher CsA concentrations (300 ng/ml) proliferation was again inhibited. Thus, CsA affected IL-2R expression and/or function at higher concentrations (300 ng/ml). CsA had no effect on receptor function as measured on IL-2-dependent cell growth of CTLL cells or preactivated lymphocytes. However, CsA inhibited both high and low affinity receptor expression as shown by [125I]IL-2 equilibrium binding studies on anti-CD3 stimulated cells. Cross-linking studies revealed that both p55 (TAC) and p75 chains of the IL-2R were not induced at low CsA concentrations (10 ng/ml). However, addition of rIL-2 reversed CsA inhibition of IL-2R expression. It is concluded that CsA, at least in anti-CD3-stimulated cells, inhibits IL-2R expression and cell proliferation with similar potency. Exogenous rIL-2 reverses CsA inhibition of IL-2R expression. This might be due to binding of rIL-2 to receptors which escape CsA inhibition, thereby up-regulating receptor expression which is drug resistant. PMID- 2312150 TI - Interaction of murine intestinal mast cell proteinase with inhibitors (serpins) in blood; analysis by SDS-PAGE and western blotting. AB - The interaction of mouse intestinal mast cell proteinase (IMCP) with serine proteinase inhibitors (serpins) in blood was analysed: (i) by examining the capacity of the inhibitors in blood to block the binding of the irreversible serine esterase inhibitor [3H]diisopropyl fluorophosphate (DFP); (ii) by Western blotting. The binding of [3H]DFP to IMCP was blocked very rapidly by inhibitors in mouse serum and, by Western blotting, this inhibition was associated with the appearance of a 73,000 MW proteinase/inhibitor complex together with a series of higher (greater than 100,000) MW complexes. IMCP was not dissociated from these complexes when electrophoresed under reducing conditions, although prior heat treatment of mouse serum (60 for 30-160 min) abolished the formation of all proteinase/inhibitor complexes. Similarly, the activity of a 48,000 MW inhibitor of chymotrypsin was abolished by heat treatment. A titration experiment established that between 0.5 and 5 mg IMCP were inhibited per ml of serum. The properties and MW of the IMCP inhibitor complexes are typical of serpins and suggest that IMCP secreted during intestinal immunological reactions would be rapidly and irreversibly inactivated by plasma-derived inhibitors. PMID- 2312151 TI - Clonal analysis of infiltrating T lymphocytes in liver tissue in viral hepatitis A. AB - The pathogenic mechanism leading to liver tissue injury in hepatitis caused by hepatitis A virus is unclear. We have randomly established T-cell clones from liver biopsies from four patients with hepatitis A. A total of 578 clones was phenotypically analysed. During the acute phase of the disease CD8+ clones dominated over CD4+ clones, whereas in a biopsy taken late after onset of clinical syndromes more CD4+ than CD8+ clones were obtained. Interestingly, in a patient with a second exacerbation of the disease, more than 20% of all clones had the CD3+ WT31- CD4- CD8- 'NK-like' phenotype. All CD8+ clones had cytotoxic activity and approximately 50% of all CD8+ clones showed specific cytotoxicity against autologous fibroblasts infected with hepatitis A virus. The CD8+ cells also produced IFN-gamma in response to these target cells. Variable IFN-gamma production was observed with all types of T-cell clones. These results suggest that the liver injury in hepatitis A is not caused by a viral cytopathogenic effect but is due to an immunopathological reaction of sensitized cytotoxic T lymphocytes against infected hepatocytes. In addition, these studies show an enrichment of CD4-8-T-cell receptor alpha beta-chain-negative T lymphocytes at the site of an inflammation and suggest a role of these cells in an anti-viral reaction. PMID- 2312152 TI - Osteoblast-like cell line maintains in vitro rat peritoneal mast cell viability and functional activity. AB - We studied the ability of the rat osteosarcoma derived cell-line with osteoblastic properties ROS-17/2.8 (ROS) to maintain in vitro rat peritoneal mast cells (MC) in a functional state. Highly purified (greater than 95%) MC were seeded on confluent ROS cells. The MC adhered tightly to the monolayers within a few hours and remained viable for at least 2 weeks, but did not proliferate. The MC retained their typical appearance, exhibiting highly granulated resting morphology when stained with alcian blue followed by safranin or with acidic toluidine blue. Furthermore, after 2 weeks, the MC were fully responsive to activation with compound 48/80 (3 micrograms/ml), releasing 75% of their histamine content, as compared to 3% in the absence of the secretagogue. Utilizing metabolically inactive ROS cells and prevention of contact between ROS and MC, we found that both release of factor(s) and cell-cell contact were required by ROS to exhibit their MC supporting activity. Various other cells and cell lines were unable to support MC viability. On the other hand, as demonstrated before, 3T3 fibroblasts were capable of promoting MC viability. Thus, MC viability and functional activity are specifically maintained by fibroblastic and osteoblastic cells. The abundance of MC in bone, and their participation in bone remodelling raise the possibility of physiological and pathological significance to interactions between MC and osteoblasts. PMID- 2312153 TI - Conditioned medium from concanavalin A-stimulated spleen cells inhibits the IgE dependent sensitization of murine peritoneal mast cells in vitro. AB - Conditioned medium (CM) from concanavalin A (Con A)-stimulated murine spleen cells inhibited release of histamine and 5-HT from murine peritoneal mast cells sensitized with monoclonal IgE anti-DNP antibody and challenged with DNP-human serum albumin (HSA) antigen. Inhibition was seen when the CM was added to the mast cells either 24 hr before or simultaneous with, but not 24 hr subsequent to, the IgE, thus showing that inhibition was at the IgE-dependent stage of mast cell sensitization. Unconditioned medium, prepared in the same way as CM but not exposed to spleen cells was without activity, demonstrating that inhibition was due to a spleen cell-derived factor. CM from unstimulated spleen cells was likewise without activity. The sensitization inhibitory factor appears to be a protein, since it was retained upon dialysis, and destroyed by heating at 70 degrees and above. The factor does not appear to be IgE, since it was stable at 56 degrees, and is not IL-1 or IL-2, since recombinant human IL-1 alpha and IL-1 beta, and recombinant mouse IL-1 alpha and IL-2 were without inhibitory activity. The active CM and all recombinant IL-1 and IL-2 preparations did not release histamine or 5-HT directly from mast cells during 48 hr of culture, and did not modulate the histamine content of these cells, nor their capacity to incorporate [3H]5-HT. PMID- 2312154 TI - Endotoxin-stimulated human macrophages produce a factor that induces polymorphonuclear leucocyte infiltration and is distinct from interleukin-1, tumour necrosis factor alpha and chemotactic factors. AB - Previously we reported that rabbit macrophages (M phi) in the presence of nanogram quantities of endotoxin (LPS) release factors that induce polymorphonuclear leucocyte (PMNL) infiltration into the skin of rabbits following i.d. injection. The predominant factor was a de novo synthesized protein of 45,000 MW on gel filtration that was distinguishable from IL-1 but not from TNF alpha. Here we examined human monocytes, in vitro monocyte-derived M phi and peritoneal M phi for the production of an analogous protein. Upon stimulation with LPS, they all rapidly (6 hr) produced a factor(s) that caused PMNL accumulation in the skin of rabbits when injected i.d. This activity, referred to as PMNL-recruiting activity (PRA), was heat labile and its production was blocked by cycloheximide. By Sephadex-G100 chromatography the major PRA of cultured M phi or peritoneal M phi had a molecular weight (MW) of 45,000-60,000. The active fractions were free of IL-1 (less than 0.2 U/ml) and Superose-12 FPLC chromatography separated the peak of PRA, which eluted at 45,000 MW, from TNF alpha, eluting at 20,000 MW. The peak PRA was not neutralized by antisera to IL-1 alpha, IL-1 beta, TNF alpha, IL-6 or GM-CSF, indicating that it was distinct from these cytokines. The major PRA did not induce the migration of PMNL in vitro in a filter chemotaxis assay. In contrast to the M phi, the major PRA produced by LPS stimulated monocytes eluted at 15,000-20,000 MW, contained IL-1 activity and was neutralized by antisera to IL-1 alpha and IL-1 beta. Monocytes from a few donors also produced the 45,000-60,000 MW PRA simultaneously. We conclude that human peritoneal M phi and in vitro monocyte-derived M phi exposed to LPS secrete a protein of 45,000-60,000 MW, which is a potent inducer of PMNL infiltration but is distinct from IL-1, TNF alpha, IL-6, GM-CSF and PMNL chemotactic factors. PMID- 2312155 TI - Regulation of interleukin-1 synthesis by histamine produced by mouse peritoneal macrophages per se. AB - The response of mouse peritoneal macrophages to Escherichia coli lipopolysaccharide (LPS) resulted in induction of histidine decarboxylase (HDC) and, consequently, of histamine production. Concanavalin A had no effect on the reactions. Alpha-fluoromethylhistidine, a suicide inhibitor of HDC, attenuated, in a dose-dependent manner, both spontaneous and LPS-stimulated IL-1 synthesis by macrophages. IL-1 production was significantly blocked by either an H1 anti histamine, diphenhydramine, or H2 anti-histamine ranitidine, in the absence of any exogenous histamine. Addition of exogenous histamine accentuated the IL-1 production by macrophages as a function of its dose. These results suggest that IL-1 production by mouse peritoneal macrophages is regulated by histamine synthesized in the system per se and that the effect of histamine is dependent on both H1 and H2 histamine receptors located on the surface of the cells. PMID- 2312156 TI - IL-2-like activity in lymph fluid following in vivo antigen challenge. AB - The majority of studies that characterize lymphokines utilize in vitro activation of lymphocytes. In an attempt to identify and characterize lymphokines released from tissue sites, we have cannulated sheep lymphatic vessels and collected lymph that drains a site of in vivo antigen challenge. Lymph draining directly from a site of intradermal antigen challenge (afferent lymph) and lymph draining an antigen-stimulated lymph node (efferent lymph) were assayed for lymphokine activity by the ability of cell-free lymph fluid to stimulate the proliferation of sheep Con A-blasts. Afferent and efferent lymph, both collected at 24 and 48 hr following in vivo antigen challenge, with either ovalbumin or PPD in primed animals, stimulates the proliferation of sheep Con A-blast cells. This in vivo derived lymphokine activity and in vitro-generated sheep Con A supernatant has an active component with properties similar to interleukin-2 (IL-2) that has been described in several other species. The IL-2-like material is precipitated by 40 80% ammonium sulphate saturation, has a molecular weight (MW) of 20,000 MW as judged by gel filtration chromatography, and is eluted from an anion-exchange HPLC column with 125 mM NaCl. HPLC ion-exchange fractionation of the 20,000 MW material from lymph fluid shows differences between afferent and efferent lymph material. The fractionation of afferent material is similar to that of in vitro generated Con A supernatant material with a single peak of activity eluted by 125 mM NaCl. In contrast, the 20,000 MW material from efferent lymph elutes with peaks of activity at 125 and 300 mM NaCl. PMID- 2312157 TI - The sensitivity of rat CD8+ and CD4+ T cells to ricin in vivo and in vitro and their relationship to IgE regulation. AB - In a previous paper we described how the toxin ricin stimulates IgE but not IgG antibody responses in rats. In this study we have examined the cellular basis for this observation. The proportion of CD4- and CD8-positive cells present in the spleen at the peak of the IgE response was determined. Those animals injected with both ricin and antigen produced a substantial IgE response (50-fold increase). Their CD4+/CD8+ ratio was also markedly increased (P less than 0.001) compared with animals given toxin or antigen alone. In addition, mitogen stimulated proliferation of mononuclear cells from spleens of the IgE-producing rats was enhanced nearly five-fold compared with cells from animals given toxin or allergen alone. The sensitivity of CD4- and CD8-positive rat spleen cells from unexposed animals to ricin in vitro was also studied. Spleen cells from untreated rats were co-cultured with optimal doses of mitogen and varying amounts of ricin. Mitogen-driven proliferation was inhibited at 10(-3) - 10(-6) mg/ml ricin. This effect was abrogated by the addition of as little as 0.01 M lactose but not by as much as 10 mg/ml mannan to the culture. Cultures depleted of CD4+ cells by rosetting were approximately 100 times more sensitive to ricin (P less than 0.01). Furthermore, the proportion of CD8+ to CD4+ cells present after culture of untreated cells with mitogen and ricin was significantly reduced. These results show (i) that the ability of ricin to increase the IgE response depends on the administration of antigen together with the toxin; (ii) that CD8+ spleen cells are more sensitive to ricin than CD4+ cells; (iii) that increased IgE responsiveness is associated with a reduction in the proportion of CD8- relative to CD4-positive cells in the spleen and increased responsiveness to mitogen. We believe that enhancement of the IgE responses by ricin may be due to inactivation of IgE-specific T-suppressor cells generated by immunization with antigen and speculate that these may be some or all of those bearing the CD8 marker. PMID- 2312158 TI - Tumour-induced immunity to H-Y-disparate skin grafts without concomitant priming of CTL. AB - A tumour, ET-5, arising as a subcutaneous mass in a C57BL/6 male mouse after treatment with a mutagen, has been found to elicit immunity to H-Y antigen in B6 female mice that have rejected the tumour. Anti-H-Y immunity is demonstrable in vivo by accelerated rejection of male skin grafts, and by the ability of spleen cells from ET-5-primed female mice to transfer immunity against H-Y antigen to immunodeficient hosts given indicator male skin grafts. However, spleen cells from ET-5-immune female mice fail to generate CTL specific for H-Y antigen when co-cultured with male stimulator cells in vitro. This finding implies that the generation of H-Y-specific immunity in vivo can occur in the absence of priming of CTL, and thus calls into question the necessity for CTL participation in H-Y disparate tumour graft rejection. PMID- 2312159 TI - A human fetal monoclonal DNA-binding antibody shares idiotypes with fetal and adult murine monoclonal DNA-binding antibodies. AB - A human DNA-binding monoclonal antibody was produced by fusing the hepatocytes from a 12-week-old human fetus with the lymphoblastoid cell line GM 4672 using polyethylene glycol. This antibody, designated BEG 2, binds to single-stranded (ss) DNA but also binds to double-stranded (ds) DNA, poly(dT), polyI and poly(ADP ribose), but not to RNA, cardiolipin or K-30. The binding of BEG 2 to these polynucleotides can be inhibited by incubation with polynucleotides in the fluid phase. A rabbit polyclonal anti-idiotype was raised, and using this reagent it was shown that the BEG 2 idiotype is present in normal human serum (7%), systemic lupus erythematosus (SLE) sera (8%) and rheumatoid arthritis sera (23%). The extent of idiotypic sharing between BEG 2 and murine monoclonal DNA-binding antibodies, in particular monoclonal antibody (mAb) 423 (derived from a 15-day old fetal MRL/Mp-lpr/lpr mouse) and mAb 402 (derived from an adult MRL/lpr mouse), was also investigated. Using a competition ELISA, it was shown that preincubation of BEG 2 with rabbit anti-423 and rabbit anti-402 inhibits the binding of BEG 2 to DNA, and the binding of 402 to DNA by anti-BEG 2 and anti 423. These data suggest that mAb BEG 2, 423 and 402 share common idiotypes, that autoreactivity is present in early fetal life, and that autoantibodies may be encoded for by germline genes, which have been conserved through evolution. PMID- 2312160 TI - Distinctive development of IgG4 subclass antibodies in the primary and secondary responses to keyhole limpet haemocyanin in man. AB - The human primary and secondary IgG subclass antibody responses to keyhole limpet haemocyanin (KLH) have been measured by ELISA using IgG subclass-specific monoclonal antibodies. KLH-specific IgG1 and IgG2 antibodies were detected 3 weeks after primary immunization, and IgG1, IgG2 and IgG4 antibodies after secondary immunization. IgG3 antibodies were observed less frequently in both primary and secondary responses. Unlike the other subclasses, IgG4 antibodies developed very slowly during the primary response, with no antibody detected at 3 weeks and often with only low titres 1 year after immunization. In one individual, this IgG4 primary response peaked around 10 months, but there was considerable variation between individuals. Comparing primary and secondary responses, the greatest increase in KLH antibody was for the IgG4 subclass (45 fold rise), followed by IgG1 (7.3-fold rise), whilst IgG2 and IgG3 KLH-specific antibodies did not show a significantly increased secondary response. There was no detectable IgG4 antibody response when secondary immunization was performed 1 month after the primary, even though IgG1, IgG2 and IgG3 antibodies were present. Reasons for the different time-course of IgG4 anti-KLH development and the isotype-related differences in 'memory' responses are discussed. PMID- 2312161 TI - Bovine IgG1, but not IgG2, binds to human B cells and inhibits antibody secretion. AB - We previously observed that milk-derived bovine IgG, but not serum-derived bovine IgG, strongly inhibits antibody secretion by pokeweed mitogen (PWM)-stimulated human peripheral blood mononuclear cells (PBMC). Bovine milk contains a greater percentage of IgG1 (90%) than does bovine serum (53%). To determine whether bovine IgG subclasses have different functional capabilities, we have examined the effects of bovine IgG1 and IgG2 subclasses upon not only antibody secretion but also mitogenesis by human PBMC. Both bovine IgG subclasses markedly inhibited PWM-stimulated mitogenesis. However, only bovine IgG1, and not IgG2, inhibited antibody secretion during a 14-day in vitro culture period. Also, antibody secretion was inhibited following a 24-hr preincubation of human PBMC with bovine IgG1, but not with IgG2. To determine whether these differences corresponded to specificities of human Fc gamma receptors on subsets of mononuclear cells, fluorescence-activated cell sorter (FACS) analyses were performed. Both bovine IgG subclasses bound to human monocytes. However, only bovine IgG1 bound to human B cells, and bovine IgG1 bound more avidly to human B cells than did human IgG. One model to explain these findings is that inhibition of mitogenesis may be due to the binding of both bovine IgG1 and IgG2 subclasses to monocytes; whereas subclass-specific inhibition of antibody secretion may result from the selective binding of bovine IgG1, but not bovine IgG2, to B cells. The observation that bovine IgG1 has a greater avidity for human B lymphocyte Fc receptors than human IgG may have important implications for future studies of Fc gamma receptors on human leucocytes. PMID- 2312162 TI - FcR blocking activity in serum of actively enhanced rat renal allograft recipients due to IgG anti-class II MHC alloantibody. AB - In some rat strain combinations, pre-operative donor-specific blood transfusion produces long-term renal allograft survival, although the underlying mechanisms are unclear. This study has examined whether Fc receptor (FcR)-blocking activity could be detected in the serum of unmodified PVG strain recipients bearing a rejecting renal allograft and in recipients bearing an actively enhanced graft following pre-operative blood transfusion. Serum harvested on Day 5 from actively enhanced PVG recipients of DA rat renal allografts was shown to specifically inhibit erythrocyte-antibody (EA) rosette formation with donor strain, but not third-party, splenocytes, while the levels of EA rosette inhibition (EAI) in Day 5 serum from rejecting rats remained markedly lower. This FcR-blocking activity was present in enhanced serum fractions, prepared by discontinuous density gradient centrifugation, which corresponded to the 7 S peak. Purified IgG prepared from enhanced serum was also found to inhibit EA rosette formation with donor splenocytes, and absorption of the IgG preparations with donor strain erythrocytes failed to abrogate EA rosette inhibition. Further experiments, in which absorbed IgG from enhanced animals was tested for FcR blocking activity against splenocytes of defined major histocompatability complex (MHC) subregion specificities, established that FcR-blocking activity was mediated by IgG alloantibodies directed against donor MHC class II antigens. Whether the presence of such antibodies early after transplantation contributes to the beneficial effect of blood transfusion on graft survival remains to be determined. PMID- 2312164 TI - Differential expression of MHC- and macrophage-associated antigens in human fetal and postnatal small intestine. AB - A panel of monoclonal antibodies against major histocompatibility complex (MHC)- and monocyte/macrophage-associated antigens was used to compare human fetal and postnatal small intestinal macrophage subpopulations. Cryostat sections were stained using an indirect immunoperoxidase technique. Within the human fetal intestine from 12 weeks gestation, the antibody KiM8 identified a widespread population of type I accessory cells, which showed variable expression of HLA-DR. In contrast, the antibody 3.9 identified small clusters of HLA-DR- and HLA-DQ positive lamina propria macrophages, presumably type II accessory cells. Comparison of fetal with postnatal small intestine revealed mainly quantitative changes, with an absolute increase in 3.9-, KiM8-, KiM6-, 10.1- and UCHMI positive accessory cells in the postnatal intestine. The proportions of both UCHM1- and KiM6-positive cells relative to the KiM8-positive population was also increased postnatally. The villous population of 3.9- and KiM6-positive interdigitating type II macrophages characteristic of the postnatal lamina propria was largely absent from fetal small intestine. The monoclonal antibody 3.9 further reacted with the cytoplasm of ganglion cells and nerve fibres within the nerve plexuses of fetal and postnatal small intestine. The significance of this cross-reactivity remains unclear. PMID- 2312163 TI - Existence of mixed isotype A beta E alpha class II molecules in Ed alpha gene introduced C57BL/6 transgenic mice. AB - In this study the existence of mixed isotype Ab beta Ed alpha molecules in Ed alpha gene-introduced C57BL/6 (B6Ed alpha) transgenic mice is demonstrated. Biosynthetically labelled B6Ed alpha transgenic spleen cells were immunoprecipitated with anti-Ab beta or anti-Ed alpha monoclonal antibody (mAb) and analysed by two-dimensional gel electrophoresis (NEPHGE/SDS-PAGE). Anti-Ab beta mAb precipitated Ed alpha molecules in addition to Ab beta and Ab alpha molecules. Anti-Ed alpha mAb precipitated Ab beta molecules in addition ot Eb beta and Ed alpha molecules. No Ed alpha molecule was precipitated by anti-Ab beta mAb from B10.A(3R) spleen cells, which have a very similar organization of class II molecules to B6Ed alpha transgenic mice. Since this B6Ed alpha transgenic mouse was shown to have 20-40 copies per cell of the Ed alpha transgene (Kashiwamura et al., 1988), it is speculated that large amounts of Ed alpha transgene are made but, according to the data presented here, only a small amount actually associates with Ab beta as opposed to Eb beta. PMID- 2312165 TI - Cleavage of a rat serosal mast cell membrane component during degranulation mediated by chymase, a secretory granule protease. AB - Exogenous addition of purified chymase, a rat serosal mast cell (RSMC) chymotryptic enzyme, results in RSMC degranulation at 37 degrees, but not at 1 degree. Chymase can cause an active site-dependent inducing event at 1 degree such that RSMC degranulation occurs if the cells are later incubated at 37 degrees. RSMC exposed to chymase or other stimuli were surface radiolabelled using 125I and Iodo-Gen, solubilized with 1% Nonidet-40, and the resulting 25,000 g supernatants analysed by SDS-PAGE and autoradiography. A 125I-labelled RSMC membrane protein of approximate 90,000 MW decreased upon exposure to either chymase or alpha-chymotrypsin (alpha-CT) for 5 min at 37 degrees or to chymase for 60 min at 1 degree. Exposure of RSMC to the secretagogues ionophore A23187, compound 48/80, and anti-IgE for 5 min at 37 degrees resulted in beta hexosaminidase (a secretory granule enzyme) release, but did not cause a detectable change in the 90,000 MW surface-labelled protein. Lima bean trypsin inhibitor, which inhibits both the esterase and RSMC degranulation activities of chymase and alpha-CT, prevented the disappearance of the 125I-labelled 90,000 MW band when added with chymase or alpha-CT. Exposure of RSMC to chymase at 1 degree for 0-10 min, prior to addition of LBTI, led to a progressive disappearance of the 90,000 MW band, which corresponded to the kinetics of priming for subsequent RSMC degranulation at 37 degrees. When RSMC were exposed to trypsin (2.5 micrograms/ml) for 0-120 min at 1 degree, a progressive disappearance of the 90,000 MW band occurred, in association with a loss of sensitivity to subsequent activation by chymase at 37 degrees. The disappearance of the 90,000 MW determinant in association with chymase-mediated priming for degranulation and the inability of chymase to mediate degranulation of trypsin-treated RSMC, which lack this membrane protein, suggests that it is involved in chymase-mediated RSMC degranulation. PMID- 2312166 TI - Release of leukotriene C4 (LTC4) from human eosinophils following adherence to IgE- and IgG-coated schistosomula of Schistosoma mansoni. AB - The release of leukotriene C4 (LTC4) from human low-density eosinophils following adherence to live or formalin-fixed schistosomula of Schistosoma mansoni coated with parasite-specific IgE or IgG obtained from pooled human anti-S. mansoni serum has been studied. IgE-rich fractions were obtained after fractionation of pooled immune sera on fast-protein liquid chromatography (FPLC; polyanion SI-17 column) and were identified by parasite-specific RAST. Contaminating IgG was removed by adsorption on a Staphylococcus aureus-protein A affinity column. IgG rich FPLC fractions were identified by a specific ELISA assay. IgG-dependent activities were confirmed by protein A adsorption. Low-density eosinophils adhered to live and formalin-fixed schistosomula coated with specific antisera and released 11.7 +/- 2.7 and 16.5 +/- 3.5 pmoles of LTC4/10(6) cells, respectively. LTC4 release induced by A23187 (5 x 10(-6) M) from the same cells was 80 +/- 24 pmoles/10(6) cells and 9.9 +/- 1 pmoles/10(6) cells in the presence of Sepharose particles (CNBr-activated 4B beads) covalently coated with normal human IgG. Fixed schistosomula coated with FPLC-purified IgE and IgG gave 7.6 +/- 0.4 and 6.0 +/- 0.1 pmoles of LTC4 per 10(6) low-density eosinophils, respectively. The same IgE- and IgG-rich fractions induced eosinophil-mediated cytotoxicity of live schistosomula in vitro. Removal of IgE by an anti-IgE affinity column abolished both the IgE-dependent release of LTC4 and the in vitro killing of larvae. Conversely, IgG-dependent activities were abolished by protein A, but not anti-IgE, adsorption. Normal density eosinophils generated undetectable amounts of LTC4 when incubated with IgE-coated schistosomula, whereas with IgG-coated larvae 4.6 pmoles/10(6) cells were obtained. Following preincubation with platelet-activating factor (PAF) (10(-7) M) and leukotriene B4 (LTB4) (10(-7) M), normal density eosinophils released LTC4 when in contact with larvae coated with antigen-specific IgE. Lyso-PAF had no effect in any of the systems tested. The synthetic chemotactic tripeptide formyl-methionyl-leucyl phenylalanine (FMLP) had no influence on IgE-dependent release of LTC4 from eosinophils. In contrast, FMLP (10(-7) M) enhanced the IgG-dependent LTC4 release, with PAF and LTB4 also showing a small enhancing effect. None of these agents substantially altered the release potential of low-density eosinophils in either IgE- or IgG-dependent events. Thus the results presented here indicate that in an IgE-dependent system, human low-density eosinophils can be induced to adhere to and kill IgE-coated helminthic targets and release biologically relevant amounts of LTC4.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2312167 TI - A thymus-independent (type 1) phosphorylcholine antigen isolated from Trichinella spiralis protects mice against pneumococcal infection. AB - A phosphorylcholine (PC)-containing glycoprotein of 68,000 molecular weight (MW) was isolated from Trichinella spiralis. The potential of this antigen (Tsp) as a species-specific vaccine against Streptococcus pneumoniae was studied in both immunologically deficient (CBA/N) and normal (CFW) mice. Unlike the PC determinant found in S. pneumoniae, Tsp is a type 1 thymus-independent (TI-1) antigen, as it was able to stimulate PC-specific antibody production in CBA/N animals, though less well than in CFW mice. Immunological memory to this antigen was observed in both strains of mice, and the predominant class of antibodies formed was IgM. In further studies, Tsp-immunized CFW mice were protected against a fatal challenge of S. pneumoniae type 3. Protection in these animals is probably mediated by the PC-specific antibodies present, which comprised 87.9% of antibodies reactive to S. pneumoniae, or 58.7% of total antibodies formed. PMID- 2312168 TI - Increased capillary permeability mediated by a dengue virus-induced lymphokine. AB - The mechanism of increased capillary permeability, seen in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), is not known. Dengue type 2 virus (DV) is known to induce production of a lymphokine, the cytotoxic factor (CF), by the T lymphocytes of mouse spleen. The data presented here show that intraperitoneal inoculation of CF in mice results in increased capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radiolabelled iodine (125I) or Evans blue dye. Peak leakage occurred 30 min after inoculation of CF and the vascular integrity was restored by 2 hr. The increase in capillary permeability was abrogated by pretreatment of mice with anti-CF antibodies, avil (H1 receptor blocker) or ranitidine (H2 receptor blocker). The findings thus show that a DV-induced lymphokine, the CF, increases the capillary permeability via release of histamine. PMID- 2312170 TI - Clonal deletion of self-Mls-reactive thymocytes at the early stage in H-2 compatible but Mls-disparate radiation chimeras. AB - Clonal deletion of T cells capable of recognizing both host-type Mls and donor type Mls occurred in the peripheral mature T-cell pool in radiation bone marrow chimeras of two H-2-compatible Mls-disparate strain combinations of AKR/J(H 2k,Thy-1.1,Mls-1a) and C3H/He(H-2k,Thy-1.2,Mls-1b). In order to determine further the stage at which the clonal deletion occurs in thymus, we examined the kinetics of thymocytes bearing V beta 6 capable of recognizing Mls-1a in both C3H/He--- AKR/J and AKR/J----C3H/He chimeras. An almost complete replacement from host derived cells to donor-derived cells occurred by Day 21 after reconstitution in both chimeras. At this stage, CD4+CD8+ double-positive thymocytes contained an appreciable number of cells that expressed V beta 6 on their surface, albeit at low intensity, whereas CD4 or CD8 single-positive thymocytes which expressed a high density of V beta 6 were virtually abolished in both C3H----AKR and AKR--- C3H chimeras on Day 21. These results suggest that clonal deletion of self-Mls reactive T cells begins at an early stage when the thymocytes interact with the early appearing donor-derived haemotopoietic cells and relatively radio-resistant host-derived cells in thymus of radiation bone marrow chimeras. PMID- 2312169 TI - Respective contribution of intracellular calcium release and extracellular calcium influx for interleukin-2 synthesis in activated T-cell hybrids. AB - Triggering of the T-cell receptor (TcR)alpha beta/CD3 receptor complex with anti allotypic antibodies or concanavalin A (Con A) induced a rapid release of intracellular calcium in a murine T-cell hybridoma model system. Internal calcium release preceded the influx of extracellular calcium, as judged by comparative analysis of time-dependent changes in Quin 2 fluorescence following T-cell activation in the presence and absence of extracellular calcium. The magnitude of intracellular calcium release and extracellular calcium influx depended on the degree of receptor-occupancy and cross-linking. Correlations between the concentration of stimulating ligand, cytosolic calcium increase and IL-2 synthesis indicated a positive but non-linear relationship. Our data suggest that TcR cross-linking may provide a third T-cell activation signal which, in conjunction with protein kinase C activation and cytosolic calcium elevation, together form a signal triad responsible for interleukin-2 (IL-2) synthesis. PMID- 2312171 TI - Patterns of nuclear proto-oncogene expression during induced differentiation and proliferation of human B chronic lymphocytic leukaemia cells. AB - Phorbol ester-induced differentiation of human B-chronic lymphocytic leukaemic cells was found to be preceded by a rapid transient induction in expression of the c-jun proto-oncogene, which paralleled that of c-fos. Induced expression of c myc but not of c-fos/c-jun proto-oncogenes was markedly higher in a proliferating variant leukaemic cell population compared with that seen in typical lymphocytic leukaemia cells. These data suggest that the c-fos/c-jun nuclear oncogenes play a role in induced differentiation, whilst c-myc is more important in the proliferative response of B lymphocytes. PMID- 2312172 TI - Therapeutics of community-acquired pneumonias. PMID- 2312174 TI - Legionella longbeachae pneumonia in a patient splenectomized for hairy-cell leukemia. AB - A 63-year-old man was admitted to the respiratory intensive care unit for pneumonia. Fifteen years earlier, hairy cell leukemia had been diagnosed and the patient underwent splenectomy. A clinical suspicion of legionellosis, later confirmed by both serology and isolation of the microorganism, prompted initiation of high dose erythromycin intravenously. The patient steadily deteriorated and passed away eight days later. This is the first reported case of hairy cell leukemia in which the diagnosis of Legionella longbeachae sero-group 1 infection was based on both serology and isolation. PMID- 2312173 TI - The role of Campylobacter (Helicobacter) pylori in disorders of the gastrointestinal tract. AB - To evaluate the role of Campylobacter pylori in different gastrointestinal disorders, serum IgG antibodies against C. pylori were determined in dyspeptic patients and in a control group of healthy children and adults. Twenty-eight percent of the dyspeptic patients with normal mucosa were seropositive. Among the patients with altered mucosa, the seroprevalence increased from duodenitis (48%) to gastritis (89%) and gastric or duodenal ulcer, gastric stump gastritis and carcinoma (100%, for each group, respectively). The C. pylori detection rate was lowest in patients with duodenitis alone (19%) and highest in patients with duodenal ulcers (95%). Therefore, C. pylori does not play an important role in patients with duodenitis alone. About 30% of patients with gastritis, active duodenal or gastric ulcer had antibody levels as low as the seroconverted dyspeptic patients but with normal gastroduodenal mucosa. C. pylori was not considered a causative factor for mucosal damage in these patients. PMID- 2312175 TI - Chemiluminescence response of human polymorphonuclear and mononuclear phagocytic cells induced by Staphylococcus saprophyticus, lectinophagocytosis versus opsonophagocytosis. AB - Two strains of Staphylococcus saprophyticus with well characterized cell surface structures were studied to determine the contribution of lectinophagocytosis versus opsonophagocytosis exerted by human phagocytic cells from five healthy donors. The luminol specific chemiluminescence assay was used to evaluate the response of phagocytes. Human polymorphonuclear leukocytes (PMNL) were demonstrated to have surface lectin receptors, since the chemiluminescence response towards both S. saprophyticus strains was inhibited by lectin-specific glycoconjugates for those organisms. Phagocytosis of S. saprophyticus by mononuclear cells was not inhibited by microbial lectin-specific glycoconjugates but was inhibited by D-mannose, suggesting that human monocytes express D-mannose specific lectins on their surface. PMID- 2312176 TI - Co-trimoxazole for visceral leishmaniasis. PMID- 2312177 TI - Fewer new cases of HIV infection in Helsinki. AB - The number of new serologically diagnosed HIV infections has decreased in Helsinki since 1986. The clinical search for infections was started in 1983 and the serodiagnostic search in late 1984. The maximum yearly number of new HIV infections was 40 cases in 1986. In 1987 and 1988 the corresponding numbers were 31 and 29, although the number of tests had increased. During the first nine months of 1989 only 16 HIV infections have been diagnosed. The levelling off, and even decrease, in the number of new cases of HIV infection gives cause for optimism about the chances of success of the campaign against AIDS by means of education, information and active screening programmes. PMID- 2312178 TI - Enhancing effect of C1q on IgG monoclonal antibody binding to hapten. AB - We have previously demonstrated that IgG antibody binding to microfilariae of Dirofilaria immitis increased in the presence of purified C1q. The present study was designed to examine the mechanism of the C1q effect using a system with an antihapten monoclonal antibody (MoAb) and a hapten as an antigen. Microtiter plates were coated with 4-hydroxy-3-nitrophenyl-acetyl (NP)-bovine serum albumin (BSA), and mouse anti-NP MoAb (IgG) was added in the presence of C1q. The amount of IgG which bound to NP-BSA increased with the addition of C1q (p less than 0.01) when the antibody had both specificity to the antigen and ability to fix C1q. The C1q effect, examined using two anti-NP MoAbs with different affinities, was more apparent with the low-affinity antibody (LAMoAb) than with the high affinity (HAMoAb; percent enhancement of IgG binding was 19 vs. 12%). The C1q effect on LAMoAb binding was doubled when a small amount of HAMoAb was incubated with LAMoAb. The C1q effect on IgG binding might be operative in the early phase of infection, where a small amount of high-affinity antibody and a relatively large amount of low-affinity antibody are produced in the host. PMID- 2312179 TI - Allergens entrapped in liposomes reduce allergenicity and induce immunogenicity on repeated injections in mice. AB - Liposomes which are nontoxic, biodegradable and biocompatible lipid vesicles are known to act as adjuvants and can be used to formulate sustained release preparation by encapsulation. In the present study, allergen entrapped in liposomes were injected at different time intervals in Swiss mice (made responders to IgE by injecting cyclophosphamide) and Balb/C mice (high IgE responders). Tissue distribution studies after intraperitoneal injection of allergen (entrapped and untrapped) revealed that liposome-entrapped allergen was retained for a longer time in all the tissues except kidney as compared to the free allergen given similarly. It was observed that serum specific IgG antibody levels were higher and specific IgE levels were lower in animals given repeated injections of liposomes-entrapped allergen as compared to those animals injected free allergen in the same manner. The entrapment of allergen in liposomes somehow suppressed the specific IgE response on repeated injections. The immunomodulatory effect of liposomes may be useful in the immunotherapy of respiratory allergic disorders. PMID- 2312180 TI - Histamine receptors on leukocytes are expressed differently in vitro and ex vivo. AB - The effect of histamine and histamine antagonists on the respiratory burst activity of leukocytes was studied. The activity was measured as zymosan-induced luminol-dependent chemiluminescence (CL) of isolated leukocytes and 1:2,500 diluted whole blood (WB). Histamine caused a dose-dependent inhibition of CL. For separated leukocytes the ID50 was 8 x 10(-5) M and for WB it was 1.5 x 10(-3) M. Diphenhydramine, an H1-antagonist increased the inhibitory effect of histamine while H2-antagonist cimetidine blocked the inhibition of CL of separated leukocytes. Cimetidine was not capable of reversing the effect of histamine on WB CL. These data suggest that the histamine receptors on leukocytes are associated with Fc and/or complement receptors and the expression and function of histamine receptors can be studied by measuring the respiratory burst activity. The results also provide evidence of differences in histamine action in vitro and ex vivo conditions in WB. PMID- 2312182 TI - Correlation between atopy and Gm allotypes. AB - In 50 consecutive atopic Caucasian patients with increased IgE greater than 600 kU/l, the phenotypic Gm allotype constellation deviated from that to be expected, with significantly increased frequency of patients with the phenotype Gm(f,n,b). There was an increased frequency of the G2m(n) allotype, more frequent in patients with IgE greater than 1,000 kU/l, and in patients with IgG4 greater than 1 g/l. In patients with IgE greater than 1,000 kU/l the phenotype Gm(a,f,n,b) was significantly increased and in patients with IgG4 greater than 1 g/l the phenotype Gm(f,n,b) was significantly increased. Those atopic patients with increased IgE and increased IgG4, according to earlier studies known to have the most severe forms of the disease, were thus mainly found to have the m(f,n,b) phenotype. PMID- 2312181 TI - Serological analysis of experimental autoimmune thyroiditis in the buffalo strain rat. AB - Previous experiments have indicated that experimental autoimmune thyroiditis (EAT) induced in the Buffalo strain of rat by neonatal thymectomy closely resembles Hashimoto's thyroiditis. In these experiments we have analysed the serology of this type of EAT. Anti-thyroglobulin (Tg) antibodies were the only thyroid autoantibodies detected by immunoblotting. The IgG subclass distribution, analysed by a monoclonal anti-rat IgG subclass ELISA, altered during the course of disease. The proportion of IgG1 subclass Tg antibodies rose and the proportion of IgG2b subclass antibodies fell as disease progressed and the relative functional affinities of the anti-Tg IgG subclasses increased as disease progressed. The sera from animals with EAT were not cytotoxic in the presence of complement to a cultured rat thyroid cell line. In conclusion, EAT does not result in the production of antibodies against heterologous autoantigens as in Hashimoto's thyroiditis. Tg antibodies are produced which have similar properties to human Tg autoantibodies, including lack of cytotoxicity, and subclass restriction; these appear to have little pathogenic role in the disease. PMID- 2312184 TI - Immunogenicity testing of food proteins: in vitro and in vivo trials in rats. AB - The immunogenicity of an industrially produced bacterial food protein (single cell protein, SCP) was analyzed in a comparative study. SCP, casein and ovalbumin were injected into or fed to rats. The systemic response was tested in vitro with a lymphocyte transformation test and in vivo with a footpad swelling assay. Feeding of casein induced cell-mediated reactivity against casein, while feeding of SCP or ovalbumin had no effect. One injection of casein led to sensitization compared with three injections of SCP. Prior feeding of SCP did not abrogate the response to injected SCP. The footpad swelling test is suggested as a particularly effective model for helping to determine the immunological risk of foodstuffs to man. PMID- 2312183 TI - Gm allotype genes and gene dosage affecting both IgG subclass and IgE levels in atopic patients. AB - The imbalanced IgG subclass levels of 50 atopic patients with IgE greater than 600 kU/l reflected the Gm expression of the patients. IgG1 was significantly increased but only in patients with the phenotypes Gm(f,f,n,n) and Gm(a,a,'',''). The typical IgG4 increase was found in the most frequent Gm(f,f,n,n) and Gm(a,f,n,'') phenotypes. Significant increase of IgG2, IgG3 and IgG4 was found in patients homozygous for G2m(n) compared to those lacking this allotype. IgG2 decrease was found in those with the Gm(f,f,'','') phenotype and IgG3 decrease in those with the Gm(a,a,'','') phenotype. Also the IgE levels were influenced by the Gm allotypes with increased IgE levels in the G1m(f,f) patients compared to the G1m(a,a) patients. PMID- 2312185 TI - Interleukin-2 receptor expression in human mast cells and basophils. AB - Surgical human thymus, upper respiratory tract, lung and small and large bowel specimens were analyzed for the presence of interleukin 2 receptor (IL2-R) positive cells. Histochemical (toluidine) and immunologic (anti-IL2-R monoclonal antibody) staining procedures revealed a distinct anti-IL2-R positivity in most of metachromatically staining cells. These positive cells were observed not only in tissues showing strong inflammatory reaction and mast cell hyperplasia, as in Crohn's disease, but also in those not histologically affected by pathologic conditions. This finding suggested that human mast cells, like T blast cells, express the p55 chain of IL2-R on their surface. To see whether IL2-R was being actively synthesized, a cell preparation rich in peripheral blood basophils (PBB), which are cells closely related to mast cells, was obtained. Ultrastructural analysis of PBB after indirect immunogold procedure revealed that the vast majority expressed the IL2-R. Moreover, the presence of intracellular reaction products in the cytoplasm of most membrane-positive PBB was indicative of active antigen synthesis. Furthermore, Northern blot analysis evidenced specific IL2-R mRNA in PBB, while its expression was augmented several times when PBB were cultured in the presence of stimulated T cell supernatant. PMID- 2312186 TI - Activation of kallikrein-kinin system in human plasma with purified serine protease from Dermatophagoides farinae. AB - An aqueous extract from a mite culture, of Dermatophagoides farinae, activated prekallikrein to kallikrein in normal plasma. Crude protein preparation, obtained by ammonium sulfate precipitation (95% saturation) from the extract, exhibited high activity (0.81 units/mg protein) towards a synthetic substrate of coagulation factor XIIa, Boc-Gln-Gly-Arg-MCA, and had also activity to form kallikrein in human plasma deficient in coagulation factor XII. Treatment of the protein preparation with phenylmethylsulfonyl fluoride (PMSF), an inhibitor of serine enzyme, gave rise to inactivation of both activities. Thus, the serine protease specific for Boc-Gln-Gly-Arg-MCA in mite cultures of D. farinae was purified by ammonium sulfate precipitation and chromatographies on p aminobenzamidine-sepharose CL-4B, DEAE-Toyopearl 650M, Sephadex G-75 superfine and Sephacryl S-200. The purified protease was homogeneous electrophoretically, and its molecular weight was estimated to be 30,000. The optimum pH and temperature were around 7.5 and 50 degrees C, respectively. The specific activity was 36 units/mg protein at pH 7.4 and 37 degrees C. The activity was completely inhibited by PMSF. The serine protease had the activity to activate the kallikrein-kinin system in normal human plasma. PMID- 2312187 TI - Enhancement of antigen-induced bronchoconstriction in the guinea pig after intravascular complement activation with cobra venom factor. AB - The purpose of the present studies was to begin to test the hypothesis that the complement system is important for antigen-induced bronchoconstriction in the guinea pig. The effect of the complement-depleting agent cobra venom factor (CVF) on antigen-induced bronchoconstriction in guinea pigs passively sensitized with IgG or IgE antibody to ovalbumin was determined. Intravenous injection of CVF significantly reduced total hemolytic complement activity (CH50), caused a transient decrease in dynamic lung compliance, an increase in pulmonary resistance, and a decrease in circulating white blood cells with a sustained decrease in platelets. Antigen-induced bronchoconstriction was not inhibited in either IgG- or IgE-sensitized guinea pigs depleted of complement. Thus, a role for the complement system as a contributing factor in antigen-induced bronchoconstriction was not supported. On the contrary, our studies revealed an enhanced antigen-induced bronchoconstriction in guinea pigs depleted of complement with CVF. Our studies were then directed towards characterizing the enhanced response to begin to determine the mechanism responsible. The enhanced antigen-induced bronchoconstriction occurred in both IgG- and IgE-sensitized guinea pigs and was most apparent at lower antigen doses. The enhanced response still occurred in animals treated for 5 min with a dose of CVF (10 U) which caused no demonstrable decrease in CH50, a 30% level of conversion of C3, and a normal response to C5a. These data suggested that the enhanced response was not related to the level of C5a responsiveness of the animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312189 TI - Value of sperm characteristics and the result of in-vitro fertilization for predicting the outcome of assisted reproduction. AB - The outcome of procedures for assisted reproduction, namely in-vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) were used as end points to assess the capacity of particular sperm characteristics to predict the fertilizing potential of semen. In addition, the result of IVF performed with spare oocytes from the GIFT procedure, was used to predict the pregnancy outcome of GIFT. The power of sperm characteristics to predict the outcome of assisted reproduction procedures was poor. With regard to the outcome of IVF, sperm morphology was the best discriminant. The threshold value of 16% normal sperm morphology could be used as a good predictor of successful IVF, but could not be applied as a criterion to reject an IVF trial. For the latter purpose, the limit of 5% sperm with normal morphology should be used. The proportion of sperm with grade A motility in native semen provided the best discrimination between GIFT fertile and GIFT-infertile cases. A negative result from IVF performed with spare oocytes was 93% accurate in predicting unsuccessful outcome of GIFT. Hence, diagnostic IVF is the most sensitive assay for male fertility. The occurrence of oocyte fertilization during IVF predicts a successful outcome of GIFT in only 50% of cases. Hence, a negative result in IVF indicates that semen is almost certainly infertile, but a positive result does not guarantee the successful outcome of GIFT. PMID- 2312188 TI - Glutathione-dependent defence mechanisms in isolated round spermatids from the rat. AB - The different mechanisms for glutathione-dependent inactivation of a number of oxidizing compounds and other xenobiotics were studied using isolated round spermatids from rats. For the estimation of cellular GSH a flow cytometric assay was used. The cells were exposed to the oxidizing compounds cumene hydroperoxide and diamide, to study the activity of the GSH redox cycle. Incubation of the isolated cells with these compounds showed that the cells had a limited capacity to withstand the oxidative stress associated with their inactivation. The GSH level of the spermatids was maintained during 18 h of incubation in the presence of low concentrations of cumene hydroperoxide and diamide, whereas spermatids exposed to higher concentrations showed a loss of both GSH and ATP. No partial loss of GSH from individual cells was observed. Diethyl maleate and 1,2-epoxy-p (nitrophenoxy)propane (ENPP) were used to study the effect of glutathione S transferase-catalysed GSH conjugation on the GSH content of spermatids. Exposure of the cells to low concentrations of diethyl maleate and ENPP resulted in a decrease in GSH content. The flow cytometric analysis showed that this was a partial loss of GSH from all cells, rather than GSH depletion in a part of the cell population. This diminution of the cellular GSH pool, however, did not affect the ATP content and viability of the cells. The present results indicate that spermatids can utilize GSH-dependent defence mechanisms against a number of model compounds. PMID- 2312190 TI - Relationship between serum testosterone and sex hormone-binding globulin in adult men with intact or absent gonadal function. AB - Serum levels of testosterone and sex hormone-binding globulin (SHBG) were determined in 80 apparently healthy men aged 25-85 years and in 23 patients with prostatic carcinoma (CAP) aged 60-75 years before and 6 months after orchidectomy. Serum levels of testosterone and SHBG were correlated positively in healthy men, in all subjects overall as well as within different age groups, and in CAP patients before, but not after, orchidectomy. These data are not consistent with the classical theory regarding SHBG regulation and also speak against an influence of SHBG binding on testosterone metabolism as a mechanism behind the observed positive association between testosterone levels and SHBG. PMID- 2312191 TI - Generation of optimum pseudorandom signals for respiratory impedance measurements. AB - Spontaneous breathing may impair the reliability of forced oscillatory impedance estimates at low frequencies, especially when the oscillatory power is distributed among many frequency values. Since the amplitude of the external forcing is limited to avoid non-linearities, it is suggested that the total energy of a composite electrical signal driving the loudspeaker be maximized at a given amplitude by finding the optimum phase relationships of the signal components, and that the low-frequency components increase in energy at the expense of the less disturbed high-frequency region. In healthy children and adults and in obstructed patients, the coherences and the coefficients of variation of the respiratory system impedance (Zrs) at 2 and 3 Hz were studied in the case of three test signals of 2-15 Hz bandwidth. Signals T1 and T2 had a flat power spectrum, whereas the components of T3 decreased sharply between 2 and 5 Hz; T1 was generated by simple random selection of phase angles, while optimization for maximum energy was done for T2 and T3. Optimization alone (T2) increased the reliability of the Zrs estimates at all frequencies, whereas enhancement of the low-frequency power (T3) resulted in a radical improvement of the estimates at 2 and 3 Hz, without loss in reliability at higher frequencies. PMID- 2312192 TI - Information statistics as applied to social interaction between mother and infant: synergic covariability vs. partial cross-covariability. AB - Behaviour can, in general, not be quantified on an equal-interval scale; therefore, the description of sequential aspects of the behaviour of two interacting individuals can not be formulated on the basis of the usual cross correlation techniques. If the information content of behaviour, however, is defined analogously to the entropy in a message, this allows a quantification of the contribution of either participant to the interaction process, and the identification of a non-additive (synergic) component in addition to the auto- and cross-covariability terms. Such a framework, based on the concept of transinformation or mutual information, was developed and realised in a suite of three FORTRAN programs. These were then applied in a longitudinal study on the development of early mother-infant interaction. The synergic term appears to increase with age in the first five months of life. This application illustrates the usefulness of information statistics for quantifying the ways in which participants contribute to a process of interaction. PMID- 2312193 TI - A new method for determination of the rate constant for clearance of radioactive indicators in gamma camera hepatography. Clinical examples with 99mTc-diethyl-IDA and 99mTc-diethyl-iodo-IDA. AB - Application of Stewart-Hamilton's formula to the activity-time curve recorded over a left ventricular region of interest following an intravenous bolus injection of a radioactive indicator in gamma camera hepatography has resulted in a new method for determination of the clearance rate constant of the indicator (i.e. the ratio of the clearance to the plasma volume). In a group of 19 normal subjects the clearance rate constant was 0.116 +/- 0.036 min-1 (means +/- 1 S.D.) with 99mTc-diethyl-IDA (SOLCO HIDA) and 0.184 +/- 0.037 min-1 (means +/- 1 S.D.) with 99mTc-diethyl-iodo-IDA (SOLCO IODIDA) in 15 normal subjects. The clearance rate constant is assumed to represent mainly hepatic clearance of the radioactive indicator and to a much smaller extent renal clearance. The literature shows diverging results as to the clearance of 99mTc-diethyl-IDA and the reasons for this are discussed. The correlations between the clearance rate constant of 99mTc diethyl-IDA and a number of laboratory variables with relation to liver function were moderate to non-existent in a group of 16 subjects with abnormal values of at least one of these variables. The rate constant for clearance as described in the paper represents a non-invasive method for rapid evaluation of the uptake capacity of the liver and, in particular, with regard to the polygonal cells of the liver parenchyma when IDA derivatives are employed. The clinical usefulness of the clearance rate constant is probably superior to the group of routine laboratory variables which also describe other functions than liver uptake. PMID- 2312194 TI - Discrete design of enzyme kinetic experiments. AB - The usefulness of discrete designs in enzyme kinetics as an alternative to continuous designs is discussed in this paper, focusing on designs satisfying the D-optimality criterion. This study has been carried out using a program called DODID, specifically devised for this purpose, which is available by request to the authors. The results presented in this paper show that the relative efficiency of the D-optimal discrete designs with respect to the continuous ones increases rapidly when increasing the number of possible values for the control variables. Relative efficiencies higher than 0.98 are achieved when using 20 possible values for each variable. The power of the tools provided by the computational approach of this work is proved by the analysis made on the robustness of different designs for estimating the kinetic parameters when a wrong assumption on the error structure has been made. The robustness of the designs made assuming medium constant error (error variance proportional to the true response) is thus confirmed. A comparative study of several discriminating designs is also presented. The results obtained show that the designs produced by adding the optimal discrete designs corresponding to both candidate models plus the point where the weighted difference between the predicted values is maximum, is a good choice when designing an experiment for discrimination. PMID- 2312195 TI - Do asymptomatic school children have normal haemodynamics 6-13 years after Mustard's operation? AB - Twenty asymptomatic school children who had undergone Mustard's operation for simple complete transposition (concordant atrioventricular and discordant ventriculo-arterial connexions) were catheterised electively 6-13 years later. The studies were carried out under general anaesthesia in air and in 100% O2. Oxygen consumption was measured and end-tidal gases were monitored using respiratory mass spectrometry. There was significant left ventricular outflow tract obstruction in 2 patients. Cardiac output in air was normal in 15 and decreased in 5 patients. The pulmonary vascular resistance was normal in 18 of 19 cases, but grossly elevated in one patient. Baffle dysfunction was present in 11 patients: 10 with important gradients between the venous pathways and the systemic venous atrium, and 5 with a leak identified either by a left-to-right shunt or by the course of the catheter. Balloon dilatation was attempted in the inferior caval venous channel in 6 and in the superior caval venous channel in 2. Mean gradient before the dilatation fell after the procedure. No pulmonary venous obstruction was identified. Even in this group of children selected as asymptomatic, approximately half had a detectable haemodynamic abnormality. PMID- 2312196 TI - The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. AB - To assess the incidence, nature and evolution of cardiac disease in Duchenne muscular dystrophy, 328 patients were studied between 1976 and 1987 for periods varying from 3 to 11 years. Patients underwent regular clinical examination, electrocardiography, echocardiography and radiological assessment. Pre-clinical cardiac involvement was found in 25% of patients under 6 years old increasing to 59% between the ages of 6 and 10 years and then declining in incidence with age. Clinically apparent cardiomyopathy is first evident after 10 years of age and increases in incidence with age, being present in all patients over 18 years of age. Its clinical impact is discussed. PMID- 2312197 TI - Congenital left atrial aneurysms: clinical characteristics and cross-sectional echocardiographic features. AB - Congenital intrapericardial aneurysm of the left atrial wall is a rare anomaly with protean manifestations. Subtle electrocardiographic and chest radiographic abnormalities often give a clue to this disease. This study describes clinical characteristics, cross-sectional and Doppler echocardiographic features of this anomaly in 4 young male patients. PMID- 2312198 TI - A spectral analysis of the high frequency QRS potentials observed during acute myocardial ischemia in dogs. AB - Electrocardiographic manifestations of transient myocardial ischemia were studied in 10 dogs undergoing occlusion of the left anterior descending coronary artery, using frequency domain analysis of the high frequency QRS potentials. Ischemia was induced via a balloon occluding cuff placed around the coronary artery. Electrocardiographic waveforms recorded before and during the ischemic state were averaged together and then filtered between 150 and 250 Hz to obtain the high frequency QRS complex. The spectral curve in the power spectrum of the high frequency QRS components was calculated using an algorithm for fast Fourier transformation. Balloon inflation was accompanied by morphological changes in the spectral curve in 7 of 10 experiments. Morphological changes, seen as zones of reduced amplitude in the time domain, appear as two separate peaks in the frequency domain. These changes were seen early in ischemia and were not accompanied by significant changes in the QRS complex or ST segment of the conventional surface electrocardiogram. The power spectrum of the high-frequency QRS potentials appears to detect evidence of transient ischemia and may provide useful information regarding the presence of myocardial ischemia. PMID- 2312199 TI - Peri-operative supraventricular arrhythmias in coronary bypass surgery. AB - One hundred consecutive admissions for coronary bypass surgery were studied to establish the incidence of peri-operative supraventricular arrhythmias, to monitor their evolution, and to identify their possible aetiological factors. No important arrhythmias were detected before the operation. Post-operatively, 24 patients (24%) developed supraventricular arrhythmias. Nineteen of them had atrial fibrillation or flutter (19%), 2 had supraventricular tachycardia (2%), and 3 had inappropriate sinus bradycardia (less than 45 min) (3%). Almost two thirds of the arrhythmias occurred within the critical early post-operative period (63%). Haemodynamic compromise ushered the onset of arrhythmias in more than one-third of the patients in whom antiarrhythmic measures ensured prompt improvement (37.5%). Three-quarters of those with atrial fibrillation or flutter were back in sinus rhythm at the time of discharge from hospital (74%). The incidence of supraventricular arrhythmia was significantly higher in patients with demonstrable myocardial ischaemia prior to surgery, in patients who underwent adjunctive coronary endarterectomy, or in those in whom topical cardiac cooling was applied (50%, 45%, and 58%, respectively). Supraventricular arrhythmias are frequently encountered during the critical early post-operative period when serious but reversible haemodynamic compromise might be precipitated. Although the nature of the underlying myocardial insult remains obscure, supraventricular arrhythmia may be related more to defective myocardial preservation than to any specific underlying myocardial lesion. PMID- 2312200 TI - Closed mitral valvotomy in pregnancy--a study of seven cases. AB - Between 1977 and 1987, seven pregnant women (mean age 28 years) had closed mitral valvotomy through a left lateral thoracotomy during their first (3 cases), second (2 cases) or third (2 cases) trimester. Surgery was necessary either because of acute heart failure with pulmonary edema not responding to medical treatment (4 cases) or to prevent the complications of severe mitral stenosis affecting either the mother or the fetus in three patients with desired pregnancies. There were neither maternal nor fetal deaths. The only complication was bleeding from a low insertion of the placenta identified in the early postoperative period in one patient that required a caesarean section, which produced a normal baby. Six pregnancies continued until term with uneventful delivery and produced normal children. We conclude that closed mitral valvotomy is a simple and a low risk procedure in pregnant women. It prevents complications of severe mitral stenosis occurring in either the mother or the fetus during pregnancy and delivery. PMID- 2312201 TI - Conduction defects in acute myocardial infarction in the Chinese in Hong Kong. AB - In order to delineate the conduction defects complicating acute myocardial infarction in the Chinese, 636 Chinese patients admitted into one of the three medical units of a general hospital in Hong Kong in the period 1973-80 were reviewed. A relatively high incidence of conduction defects was observed, including atrioventricular block (11.3%), right bundle branch block (12.7%) and left bundle branch block (3.3%). Right bundle branch block (whether isolated or combined with left fascicular block) and atrioventricular block complicating anterior Q-wave infarction were ominous, with a high incidence of pump failure, cardiogenic shock and cardiac arrhythmias. These are markers of massive infarction. Atrioventricular and bundle branch blocks complicating inferior Q wave infarction were benign. Left bundle branch block appeared to be a more chronic lesion, with moderate mortality, and isolated left anterior hemiblock did not adversely affect the short-term outcome. These results conform well to the patterns seen in Western series. The high incidence of conduction defects, in particular right bundle branch block and atrioventricular block complicating anteroseptal infarction, indicates a more serious clinical spectrum of acute myocardial infarction in the Chinese, and could have contributed to a higher hospital mortality in the Chinese series. PMID- 2312202 TI - The haemodynamic response to ST segment changes during coronary arteriography. AB - Contrast media are known to cause electrocardiographic and haemodynamic changes during coronary arteriography. There is a tendency to proceed with repeated coronary arteriography unless patients develop chest pain, bradycardia or hypotension. We have related the changes in the ST segment to changes in left ventricular end-diastolic pressure, measuring pulmonary arterial diastolic pressure with a transducer tipped catheter. Twenty-five patients were studied, 15 patients with coronary arterial disease, 2 with syndrome X, 3 with coronary arterial spasm (and underlying coronary disease) and 5 normal controls. In control patients, no changes in the ST segment or pulmonary arterial diastolic pressure were recorded. Patients with syndrome X developed ST segment depression in the absence of changes in pulmonary arterial diastolic pressure. Those with coronary arterial spasm and underlying coronary disease developed ST segment depression and a rise in pulmonary arterial diastolic pressure following most injections. In coronary arterial disease, both painful and silent ST segment depression was noted with a rise in pulmonary arterial diastolic pressure. In some instances, a summation effect arose with repeated injections. Major disturbances in the ST segment may occur during coronary arteriography and result in elevation of left ventricular filling pressure. PMID- 2312203 TI - Reproducibility of echocardiographic estimates of the area of stenosed aortic valves using the continuity equation. AB - Interobserver variability in echocardiographic estimates of the area of stenosed aortic valves was assessed in 30 consecutive patients. Using the continuity equation, two independent observers calculated the area of stenosis from separate recordings of the diameter of the aortic orifice and the velocity time integral in the left ventricular outflow tract and in the stenotic jet. No significant difference between the observers was noted for any measurement. With respect to the area of stenosis, a high correlation between the observers was found (r = 0.92, P less than 0.001) and the regression line was close to the line of identity. The 95% limits of agreement were less than +/- 0.3 cm2. No discrepancy between the observers was found in the assessment of cases for aortic stenosis less than 0.8 cm2. Regression analyses showed good interobserver agreement also for the diameter of the orifice, the velocity time integrals, and the mean pressure gradient (r greater than 0.90, P less than 0.001). The greatest variability was noted for the diameter of the aortic orifice (95% limits of agreement +/- 1.4 cm2). We conclude that echocardiography enables reproducible estimates of the orificial area of stenosed aortic valves. Changes greater than 0.3 cm2 can be detected with a confidence probability of 95%. The greatest source of error is the measurement of the diameter of the outflow tract at the basal attachments of the aortic leaflets. PMID- 2312205 TI - Unusual "high take off" of the right coronary artery from the ascending aorta. AB - An exceedingly rare anomaly is described in which the right coronary artery originated two centimetres above the left posterior sinus of Valsalva in association with an aortic valve having two leaflets. PMID- 2312204 TI - The relationship between growth of atherosclerotic plaques, variant angina and sudden death. AB - Clinico-pathological findings are described in two patients with typical variant angina who died suddenly during an ischemic attack. In both cases, detailed pathologic examination of the coronary arteries disclosed severe focal atherosclerosis of the anterior descending coronary artery. The only distinctive histological finding was new intimal proliferation of smooth muscle cells enmeshed within mucoid substance, superimposed on the old fibrous cap of the plaque. These findings agree with experimental and clinical data which suggest that coronary vasospasm may be related to growth of atherosclerotic plaques. This study provides histological evidence that progression of an atherosclerotic plaque may underlie variant angina and sudden death. PMID- 2312206 TI - Atrioventricular septal defect with intact septal structures in a 74-year-old. AB - We report the incidental finding at post mortem of deficient atrioventricular septation in the heart of a 74-year-old woman. A review of her clinical history showed little indication of this lesion. The heart had intact septal structures but exhibited other features pathognomonic of atrioventricular septal defect. PMID- 2312207 TI - Importance of abstention from alcohol in alcoholic heart disease. AB - A case of alcohol-associated heart disease, presenting with congestive heart failure, was followed for 36 months. After abstinence from alcohol, fractional shortening rose from 13 to 60%. After 1 1/2 years of abstinence and normal physical capacity, the alcoholic abuse was resumed. Eleven months later, the patient was again in overt heart failure. Withdrawal of alcohol was again associated with significant clinical improvement, but despite being in functional NYHA class I, fractional shortening only increased from 14 to 29%. Endomyocardial morphology was unrelated to the severity of the disease. Alcoholic heart disease is partially reversible, but total abstinence is necessary to preserve cardiac function. PMID- 2312208 TI - Intermittent to-and-fro murmur in cardiac pseudoaneurysm: Doppler echocardiographic findings. AB - A case is presented in which a to-and-fro murmur was heard at auscultation. Cross sectional echocardiography, combined with Doppler examination, showed that the murmur was produced by flow across the neck of a left ventricular pseudoaneurysm. PMID- 2312209 TI - Myocardial infarction following sublingual administration of isosorbide dinitrate. AB - A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency. PMID- 2312210 TI - Criss-cross heart with intact ventricular septum. AB - We report a case of a criss-cross heart in a 6-month-old male child with echocardiographic and angiocardiographic findings of concordant atrioventricular and discordant ventriculoarterial connexions and an intact ventricular septum. This entity has been described with a ventricular septal defect as part of its own anatomic spectrum. The concept of the criss-cross heart, however, is best restricted to a form of spatial atrioventricular arrangement in which the atrioventricular connexions are criss-crossed. PMID- 2312212 TI - Heterogeneity of personality traits in massive obesity and outcome prediction of bariatric surgery. AB - The search for heterogeneity of personality characteristics amongst the massively obese is extended to a larger sample (n = 215) of both males (n = 83) and females (n = 132). The Minnesota Multiphasic Personality Inventory standard scales serve as the data base for a cluster analysis which has yielded four clusters: cluster 1 (n = 36) where all scales fell well within normal limits; cluster 2 (n = 112) was coded as 3-1 and was also within normal limits; cluster 3 (n = 44) was coded as spike 4; and cluster 4 (n = 23) was coded as 2-1-7-3-8-4. Cluster membership was not related to surgeons' four-year follow-up overall outcome rating. Discriminant function analysis yielded two variables (patient age and MMPI scale 1 T-score) which were significant predictors of subsequent outcome. The results suggest that there is heterogeneity of personality traits among the massively obese and offer encouragement to the search for variables that are even more effective predictors of the outcome of bariatric surgery. PMID- 2312211 TI - Sexual activity and coronary arterial disease. PMID- 2312213 TI - In vivo studies of lipid metabolism in lean and pre-obese swine. AB - Selection for high and low backfat in swine has resulted in obese and lean strains of swine. Fetuses (110 days) from obese dams (HF fetuses) when compared to fetuses from lean dams (LF fetuses) have larger fat cells, higher rates of palmitate esterification in adipose tissue and much higher levels of adipose tissue lipoprotein lipase (LPL) activity. In the present study an exogenous lipid load was given to HF and LF fetuses; lipid uptake into adipose tissue and liver was quantified as was the clearance of lipid from the blood. Uptake of lipid by liver was significant and similar for HF and LF fetuses. However, adipose tissue from HF fetuses took up significantly more lipid than did adipose tissue from LF features. Likewise, lipid clearance was greater in HF fetuses than in LF fetuses. Therefore, the amount of LPL activity in fetal adipose tissue is indicative of the functional capacity of the adipocytes to take up lipid and remove it from the blood. PMID- 2312214 TI - Long-term actions of d-fenfluramine in two rat models of obesity. II. Responses to stress. AB - In the previous study (part I), we reported that a 28-day regimen of d fenfluramine administered via osmotic pump sustained weight reductions in normal weight and obese rats without depleting brain 5-HT. Peripheral actions of d fenfluramine were also examined. Here we extend those findings to night-time observations and to stressful conditions. This treatment regimen had no effects on night-time concentrations of insulin, triglycerides or corticosterone or on the stress-induced rise in triglycerides and corticosterone. The thermic response to cold was unaltered. Glucose tolerance was enhanced in lean, but not obese rats. PMID- 2312215 TI - A longitudinal study of obesity in Japan: relationship of body habitus between at birth and at age 17. AB - To clarify the relationship between body habitus from birth to adolescence, changes in weight and height of 309 boys and 335 girls were observed at birth, 3, 6, 11, 14 and 17 years old. Body mass index (BMI = W/H2) was calculated to estimate their habitus at birth, 3 and 17 years, and Rohrer index (W/H3) was used for 6, 11 and 14 years habitus. We define the children in the top decile as obese and those in the bottom decile as lean. Among girls obesity at 17 years old is already related to habitus at birth, while among boys it is related to habitus at 3 years old. Based on these results, we tentatively recommend that prevention of obesity should start as early as possible, at the least from 3 years old. PMID- 2312216 TI - Bile acid malabsorption after intestinal bypass surgery for obesity. A comparison between jejunoileal shunt and biliointestinal bypass. AB - Seventeen patients were operated on with intestinal shunts for morbid obesity, in eight a biliointestinal bypass (BI) was constructed and in the rest a conventional jejunoileal (JI)-shunt. The reduction in weight was similar in both groups, and so was malabsorption of fat, but the BI-group had significantly less bowel motions with less watery diarrhoea. Bile acid malabsorption was measured both chemically by estimating the total amount of faecal bile acids excreted, as well as indirectly by using a 75Se-labelled synthetic bile acid (SeHCAT). Both techniques revealed a substantial loss of bile acid after both types of operation, but patients with BI bypass surgery had significantly lower elimination time of the bile acid than those with JI-shunts. There was a significant negative correlation between SeHCAT retention and total faecal bile acids. However, some patients with low SeHCAT retention had normal or even reduced output of faecal bile acids. Estimation of faecal bile acids may display false negative results when the bile acid pool is decreased. The SeHCAT-test seems to be a better technique for measuring bile acid losses. The study suggests that BI bypass surgery for obesity seems to be advantageous over the JI shunt in reducing the postoperative loss of bile acids and choleretic diarrhoea, without influencing the weight loss. PMID- 2312217 TI - Long-term exercise training with constant energy intake. 3: Effects on plasma lipoprotein levels. AB - The composition and concentration of plasma lipoproteins were studied in five young men (mean BMI = 27.5 +/- 2.9 (s.d.] before, during (after 25 and 50 days of training), and after the completion of a 100 day exercise training program that induced daily 4.2 MJ calorie deficit. Along with reductions in body weight (from 86.7 +/- 20.0 to 78.7 +/- 17.1 kg, P less than 0.01) and in fat mass (from 17.0 +/- 9.7 to 10.4 +/- 7.4 kg, P less than 0.01), the exercise training program induced numerous changes in plasma lipoprotein levels. Plasma total cholesterol level fell significantly after 25 days of training (P less than 0.05) and remained significantly reduced at the end of the training experiment (P less than 0.05). This reduction in total plasma cholesterol was accompanied by reductions in plasma apoprotein (apo) B, LDL-cholesterol and LDL-apo B levels (P less than 0.05). There were trends for reductions in plasma triglyceride and VLDL components that were significant only for VLDL-triglycerides (P less than 0.05). Plasma HDL-cholesterol levels increased significantly only at the end of the training program (P less than 0.01). This increase in plasma HDL-cholesterol was not accompanied by an increase in plasma apo A-I levels suggesting that exercise training produced an increase in HDL cholesterol content rather than an increase in HDL particle number. Ratios of HDL-cholesterol/cholesterol (P less than 0.01) and apo A-I/apo B (P less than 0.05) were significantly increased by exercise training, suggesting a decreased risk of cardiovascular disease. These results indicate that a reduction in fat mass solely induced by aerobic exercise training has substantial beneficial effects on plasma lipoprotein levels. PMID- 2312218 TI - Seasonality of two gill monogeneans from two freshwater fish from an oligotrophic lake in northeast Finland. AB - The seasonal occurrence of Dactylogyrus amphibothrium and Discocotyle sagittata from the gills of ruffe (Gymnocephalus cernuus) and whitefish (Coregonus acronius), respectively was studied in Lake Yli-Kitka, a large oligotrophic lake in Northeast Finland. The lake, located near the Arctic Circle, is ice-covered for 7-8 months of the year. The prevalence of D. amphibothrium infection was 70.7% and remained high throughout all size-classes of fish. The length distribution and developmental stages of the worms indicated two generations per year. The overwintering generation produces a summer generation which lives for only a few weeks and matures in July. Discocotyle sagittata has only one generation yearly. Its worms mature and produce eggs in July-August and recruitment of the new generation starts in the autumn. The prevalence of D. sagittata infection varied between 40% (in January) and 6.7% (in September); smaller fish were more heavily infected than larger fish. PMID- 2312219 TI - Biochemical variations in Gigantocotyle explanatum and Gastrothylax crumenifer with respect to their seasonal reproduction. AB - Biochemical components, glycogen, protein, nucleic acids and lipid fractions were analysed every month from January to December 1986, in the liver and rumen amphistomes Gigantocotyle explanatum and Gastrothylax crumenifer, respectively. The results reveal a considerable seasonal variation. In the rumen amphistome the components reach their maximum level only once a year, whereas in the liver amphistome, more than one peak is observed in a year. In G. crumenifer the content of glycogen and nucleic acids increases before the onset of egg production while protein and lipids reach their maximum level during the egg production phase. The variations in biochemical components were associated with the reproductive cycles and gonad recrudescence of these parasites. PMID- 2312220 TI - Experimental infection of Thailand Taenia (Chiengmai strain) in domestic animals. AB - Twenty-five gravid proglottides of a Thailand Taenia were obtained from a patient in Chiengmai, Thailand, and brought to our laboratory. The tapeworm was determined to be T. saginata-like by counting uterine branches (mean number 16, range 12-19 on each side). The eggs from these proglottides remained infective under storage at room temperature for 14 days followed by refrigeration (4-8 degrees C) for 131 days. Eight Small-Ear-Miniature pigs and two Holstein calves were each fed with 3000 eggs and sacrificed 12-76 days afterwards. Six pigs became infected and 16 cysticerci were recovered from the livers. Thirteen degenerated/calcified cysticerci were also recovered from the livers of the two calves. More cysticerci were found in the liver parenchyma (55%) than on the liver surface (45%) of the infected animals. Measurements of length, width, diameters of protoscolex, rostellum and sucker and hooklet pattern show that Thailand Taenia is similar to Taenia from Taiwan, Korea and Indonesia but different from T. saginata and T. solium. These findings indicate that Thailand Taenia, Taiwan Taenia, Korea Taenia, and Indonesia Taenia may be of the same species or sub-species. PMID- 2312221 TI - Single- and five-worm infections of Echinostoma caproni (Trematoda) in the ICR mouse. AB - Twenty-nine (64%) of 44 ICR mice fed a single metacercarial cyst of Echinostoma caproni and all of 23 mice each fed five cysts were infected with ovigerous worms at necropsy 2-4 weeks post-infection. Each host fed five cysts had two to five worms at necropsy, and all worms were either paired or clustered. Distribution of worms in the small intestine was similar in single- and five-worm infections and all worms were located 17-20 cm anterior to the ileo-cecal valve. Both single and multiple worms produced eggs with fully-developed miracidia. The number of eggs per uterus in 2-week-old multiple worms was almost twice that of single worms. The body area of 3- and 4-week-old multiple worms was significantly greater than that of single worms of the same age. PMID- 2312222 TI - Application of 15N-nuclear magnetic resonance (N.M.R.) spectroscopy for the study of nitrogen metabolism of a parasite: transamination in Angiostrongylus cantonensis eggs. AB - In an attempt to study nitrogen metabolism in a parasite, we applied 15N-nuclear magnetic resonance (NMR) technology with a stable isotope, a 15N-labeled compound, for the study of the transamination system in A. cantonensis eggs, and demonstrated that 15N-aspartic acid can serve as an amino group donor for both the 2-oxoglutaric-glutamic acid and the pyruvic acid-alanine transamination systems in the eggs. PMID- 2312223 TI - Cloning of a species-specific DNA probe from Onchocerca gibsoni. AB - A genomic library of Onchocerca gibsoni has been prepared in the vector lambda gt10 and has been screened for specific DNA sequences by hybridization with radiolabelled total genomic DNA from a number of Onchocerca species. A clone- fOGI--has been isolated which does not interact with DNA prepared from O. gutturosa, O. lienalis, O. ochengi, O. cervicalis or O. volvulus (both Liberian and Mexican isolates). In addition, no hybridization is observed with host (cattle) DNA. fOGI can detect as little as 100-200 pg of O. gibsoni DNA. It is thus concluded that fOGI has the sensitivity to detect microfilariae of O. gibsoni found in the skin of cattle and the specificity to differentiate them from closely related species living in the same environment. PMID- 2312224 TI - Pyrimidine salvage pathways in adult Schistosoma mansoni. AB - Adult Schistosoma mansoni can utilize radiolabelled cytidine, uridine, uracil, orotate, deoxycytidine and thymidine for the synthesis of its nucleic acids. In this respect, cytidine is the most efficiently utilized pyrimidine precursor. Cytosine, thymine and orotidine are transported into the parasites but not metabolized. High performance liquid chromatography analysis of the nucleobase, nucleoside and nucleotide pools from in vivo metabolic studies and assays of enzyme activities in cell-free extracts indicate the presence of nucleoside and nucleotide kinases which phosphorylate the various nucleosides to their respective nucleoside mono-, di- and triphosphates. Uridine, thymidine and deoxyuridine can also be cleaved to their respective nucleobases by uridine phosphorylase. Uracil can be converted directly to UMP by orotate phosphoribosyltransferase or by the sequential actions of uridine phosphorylase and uridine kinase. Nucleoside 5'-monophosphates were dephosphorylated by active phosphohydrolases. All enzymes tested were found in the cytosol fraction with the exception of the phosphohydrolases which were associated mainly with the particulate fraction. No deamination of cytosine, cytidine, deoxycytidine, CMP or dCMP was detected either in vivo or in vitro. The active metabolism of cytidine and absence of deamination and phosphorolysis of cytidine derivatives in schistosomes raise the possibility of using cytidine analogues for the selective treatment of schistosomiasis. PMID- 2312225 TI - The egg bundles of the monogenean Dionchus remorae and their attachment to the gills of the remora, Echeneis naucrates. AB - Gills of three remoras, Echeneis naucrates L., from Heron Island, Queensland, Australia had few adults but many attached egg bundles of the monogenean, Dionchus remorae. Studies of fresh, and preserved and cleared, primary gill lamellae bearing egg bundles and investigations with scanning electron microscopy and serial wax sections reveal proliferated host epithelium surrounding and embedding part of a loop of egg-shell material to which eggs are tethered, but eggs in each bundle hang free of gill tissue. This hyperplasia appears to anchor egg bundles to the host's gills. However, hyperplasia will take time to develop and cannot play a part in tethering newly laid egg bundles. Possible advantages to the parasite by attaching eggs to the gills of its host include improved oxygenation of the eggs, and a reduced risk of egg predation. Egg attachment by D. remorae to their remora hosts seems well adapted to successful larval invasion of fish which exhibit phoresy. PMID- 2312226 TI - The development of an enzyme-linked immunosorbent assay for Trypanosoma vivax and its use in a seroepidemiological survey of the Eastern Caribbean Basin. AB - An enzyme-linked immunosorbent assay (ELISA) for IgG antibodies against a South American (New World) strain of Trypanosoma vivax was developed and used for mass screening of cattle from 20 islands in the Eastern Caribbean Basin. The sensitivity and specificity of antigens prepared from a bovine-derived field strain and a murine-adapted laboratory strain of T. vivax, both of New World origin, were compared using an indirect fluorescent antibody (IFA) test, and an antigen prepared from the murine-adapted strain was subsequently used to develop an ELISA test. The results of the ELISA test were then compared with the results of a concurrently run IFA test. There was no cross-reactivity with either test using serum from a Trypanosoma theileri-infected cow. Both tests were weakly cross-reactive with sera from a T. brucei-infected steer, and the IFA test was moderately cross-reactive with several serum samples from a T. evansi-infected steer. For bovine sera collected from herds on islands in the Eastern Caribbean region, only five of 640 tested positive with the ELISA test. Thirty five of 653 sera tested were positive by IFA although the fluorescence elicited was weak as compared to that elicited by sera from known infected animals. Sera collected from 27 cattle in a region known to be free of T. vivax (OH, U.S.A) were negative with the ELISA test, whereas seven of 30 sera from a herd in French Guiana known to be infected with T. vivax were positive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312227 TI - Strongyloides venezuelensis infections in mice. AB - The course and intensity of Strongyloides venezuelensis infection as compared with S. ratti infection were investigated in BALB/c mice. The mice were found to be much more susceptible to infection with S. venezuelensis than S. ratti. The majority of worms inoculated were recovered from the lungs and subsequently from the small intestines, suggesting that their migratory route via the lungs to the small intestine was comparable to that of S. stercoralis in humans. Spontaneous expulsion of worms occurred by about 10 days after infection, which was the same as that of S. ratti. Different infectivities, as assessed by faecal egg excretion, age, sex and strain of mouse were observed in mice infected with S. venezuelensis, as well as in those infected with S. ratti. A striking immunity was acquired following a primary exposure to S. venezuelensis. Mice infected with S. venezuelensis are considered to provide as useful a model as those infected with S. ratti for the study of human strongyloidiasis. PMID- 2312228 TI - Effects of spleen cells and serum on transfer of immunity to Strongyloides venezuelensis infection in hypothymic (nude) mice. AB - The course of Strongyloides venezuelensis infection in congenitally hypothymic (nu/nu) mice and their heterozygous thymus-bearing littermates (nu/+) was followed. Unlike the infected nu/+ mice, the nu/nu mice were unable to expel the worms until the end of the observation period (98 days post-infection). In addition, about three times as many eggs were counted at the peak level of infection in faeces of the infected nu/nu mice in comparison with the nu/+ mice. No acquired resistance to rechallenge was observed among the nu/nu mice. Auto reinfection within the infected nu/nu mice could not be supposed in the present study. The worm expulsion mechanism was generated by nu/nu mice which had been given syngeneic spleen cells from intact +/+ mice. The expulsion of adult worms, as well as the protection against migrating larvae, occurred anamnestically when spleen cells from immune +/+ mice were transferred. The serum transfer, however, only caused a retardation of larval migration. The results support the hypothesis that direct worm immunity and worm expulsion are a T cell-dependent phenomenon. PMID- 2312229 TI - Increased glucose permeability in Babesia bovis-infected erythrocytes. AB - Glucose influx into bovine erythrocytes was found to be significantly increased upon infection with the parasite, Babesia bovis. The influx of glucose into the infected cells over 4 min was not saturable at high concentrations of glucose (240 mM), nor was it affected by established inhibitors of mammalian glucose transport, such as cytochalasin B and phloretin (0.1-100 microM). Glucose uptake into the parasitized cells was, however, inhibited by phloridzin (phloretin-2 beta-glucoside) at concentrations over the range of 10-500 microM. Further inhibition of glucose uptake by adenosine (2.5-15 mM) was found to occur in B. bovis-infected bovine erythrocytes, suggesting an interaction of adenosine with the new or altered component of glucose transport in the parasitized cells. PMID- 2312230 TI - Evaluation of pyrantel-tartrate abbreviated Ascaris suum infections for the development of resistance in young pigs against migrating larvae. AB - Crossbred young pigs were used to test whether abbreviated infections with eggs of Ascaris suum can stimulate the acquisition of resistance to challenge. Weanling pigs from an Ascaris-free colony were kept free of A. suum until they were divided into groups at the age of 7-8 weeks. The experimental animals received pyrantel tartrate during the period when they were being exposed to increasing numbers of infective A. suum eggs and challenged 10 days after the last infective dose. Liver milk-spot counts and larval recoveries from the lungs indicated that the strongest resistance was acquired by the animals that received the drug continuously for 6 weeks while being exposed to six weekly infective egg doses. The data do not suggest any drug-related suppression of the resistance response to A. suum infection. PMID- 2312231 TI - Comparison of the viability and developmental characteristics of Echinococcus multilocularis isolates from human patients in France. AB - Alveolar echinococcosis, due to E. multilocularis, is usually a fatal disease in patients whether treated by benzimidazolecarbamates or not. However, aborted infections have been described, suggesting the existence of strains of parasites of varying pathogenicity. These observations led us to analyse the viability of larvae in 20 patients. After observation of human lesions, the viability of metacestodes was tested by intraperitoneal infection in two intermediate host species, Meriones unguiculatus and AKR inbred mice. Parasitic development was more frequent in mice than in M. unguiculatus, but in the latter, growth was more rapid and the larval mass produced was greater. Isolates which originated from patients undergoing treatment had an abortive growth; two others were characterized by a steady, though slow, development, producing a poorly budding larva; lastly there were some which were morphologically similar with a multivesicular appearance but differing development times. These results may serve as a guide for more basic studies leading to an understanding of the problem of intraspecific variations in E. multilocularis. PMID- 2312232 TI - Temperature effects on survival and excystment of cercariae of Halipegus occidualis (Trematoda). AB - Survival of the cystophorous cercariae of Halipegus occidualis (Trematoda: Hemiuridae) from naturally infected Helisoma anceps (Gastropoda: Planorbidae) was determined following constant temperature storage at 4, 16, 22, 26 and 30 degrees C. At 4 degrees C, 90% of cercariae survived for 14 weeks and 50% survived for 30 weeks. Survival varied inversely with temperature, and at 30 degrees, 90% survived for 1.5 weeks and 50% survived for 2.5 weeks. At the time of release from snails, cercariae excysted within 0.5 s of stimulation. Excystment times ultimately increased to 1-3 s at all temperatures as length of storage increased, but no connection was detected between excystment time and the activity of the cercaria. Excystment times began increasing while survival was still above 90%. Temperature specific mortality rates of cercariae were estimated, and used to simulate the survival of cercariae released naturally at various times of the year. The results of these simulations suggest that cercariae of H. occidualis are present in the environment at all times of the year, but that cercariae present in late winter (January to mid-March) may have an impaired excystment mechanism that reduces their infectivity. PMID- 2312233 TI - Determinants of early infant weaning: a multivariate approach. AB - This research provides a multivariate analysis of factors associated with prolonged breast-feeding and conversely early infant weaning. Infant care practices associated with early infant weaning during the first four months of life were: early introduction to artificial milk, the infant sleeping in its own crib versus with its mother, and in general a more rigid feeding schedule. The weaned infant lived in a family with higher economic means, also maternal employment and the availability of a support person to care for the infant were variables more frequently found among infants weaned early. These infants had greater than average numbers of curative health care visits and gained less weight during the first four months of life than breast-fed infants. This study's findings suggest that as changes in life styles and cultural norms are molded by levels of modernization and urbanization, with greater participation of women in the workforce, the tendency to wean early may become even greater. PMID- 2312234 TI - Determinants of pain assessment by nurses. AB - In this replication study pain assessment and patient perception by nurses was studied in relation to patient characteristics and nurse characteristics. Nurses were randomly assigned to one of 24 descriptions of a hypothetical patient of constant age and unspecified sex. The 24 descriptions varied by duration of pain, presence of a physical pathology, diagnosis category, and depression symptoms. Results showed that third- and fourth-year student nurses of a hospital based program, and registered nurses attributed more pain when test results of physical pathology were positive. Third- and fourth-year student nurses also attributed more pain to depressive patients. No differences were found with respect to pain duration and diagnostic category. Nursing experience seems also to be important in pain assessment. First-year student nurses attributed less pain to the hypothetical patient than third- and fourth-year student nurses and registered nurses. In addition they perceived the patient as more positive when physical pathology was present or when no symptoms of depression were present. PMID- 2312235 TI - Health promotion as a nursing function: perceptions held by university students of nursing. AB - Health care in Australia is more often perceived to be illness rather than health focused in nature. The increasing cost of health care has prompted a movement towards health promotion in the community demanding increasing involvement of health care professionals. This three year study was undertaken to determine the attitudes of students towards health promotion on entry and throughout a tertiary nursing programme. This longitudinal study was exploratory in nature and examined the attitudes of two student cohorts over the programme's three years. Entering students cited the health promotion function more frequently than did those nearing programme completion. There is a need to emphasise health promotion as a role if this is seen as desirable behaviour for comprehensively educated nurses. The perceptions of three intakes of students were examined. The function of health promotion was perceived to be important by entry students and was within the three most frequently mentioned functions. PMID- 2312236 TI - The QUALCARE Scale: developing an instrument to measure quality of home care. AB - In previous research, the theoretical and methodological problems associated with operationalizing elder abuse have been multiple. The QUALCARE Scale was developed in response to the documented problems. The scale is an observational rating scale designed to quantify the quality of family caregiving to home-dwelling elders in six areas: physical, medical management, psychosocial, environmental, human rights and financial. The scale is a 53 item scale in a Likert type format. The QUALCARE Scale is completed by professional nurses after a nursing assessment of the degree to which the caregiver meets the needs of the elder in the six dimensions. The nursing assessment involves both observations and verbal data gathering. In this paper, the development of the scale and the methodological issues associated with scale development are discussed. PMID- 2312237 TI - The QUALCARE Scale: testing of a measurement instrument for clinical practice. AB - This article continues the discussion of the theoretical and methodological issues associated with the use of measurement instruments in nursing such as the QUALCARE Scale. The QUALCARE Scale is an observational rating scale designed to quantify the quality of family caregiving to home-dwelling elders in six areas: physical, medical management, psychosocial, environmental, human rights and financial. This manuscript continues the discussion by reporting the psychometric properties of the scale. The QUALCARE Scale was tested in a descriptive correlational study with 249 caregiver-elder dyads. The results supported evidence of interrater reliability, internal consistency, and criterion and construct validity. Three issues in the use of measurement instruments in clinical practice are discussed: (i) quantification versus qualification, (ii) clinical relevance and (iii) the establishment of rating standards. PMID- 2312238 TI - ICN receives WHO support for AIDS project in Africa. PMID- 2312239 TI - WHO: dire forecast on AIDS spread worldwide. PMID- 2312240 TI - Transcultural nursing assessment: a method for advancing nursing practice. AB - Today a new generation of nurses with different cultural insights and a deeper appreciation of human life and values are developing a sensitivity for culturally appropriate individualized care. Although literature on clinical approaches in cultural diverse situations is mushrooming, relatively few theories on transcultural nursing provide a systematic method for comprehensive nursing assessment, which is necessary for both the nursing practitioner and the researcher to provide appropriate nursing care tailored for each client. Below an outline of the areas that need to be assessed when working with clients from multicultural populations. PMID- 2312241 TI - A common sense approach to nursing research. AB - Two events conspired to force me to develop and then articulate a political or power perspective on nursing research. During my term as president of the American Nurses' Association (ANA) experience taught me that knowledge is the currency of politics--politics defined broadly as governance by the institution, by the profession, by the industry or by the Congress. Data describe. Data explain. Data persuade. And, where the mind is made up, data justify. The second event was the June 1988 meeting in Jerusalem of the Workshop of European Nurse Researchers (WERN) where I was invited to speak on The Power of Knowledge: The Knowledge of Power. This was the challenge to put into words what I had learned on this subject throughout a career as academician topped with a tour in professional politics. The result is a common sense approach to nursing research that I would like to present to the nursing community for further debate. PMID- 2312242 TI - Nurses as a key PHC link in Papua New Guinea. AB - While many developing countries have endorsed primary health care (PHC) as a means of reaching Alma Ata's goal of health for all, effective implementation has been difficult. The major obstacle has been the historic emphasis on curative medicine in the training, licensing and job responsibilities of health care personnel and in the distribution of scarce resources. Moreover, few programmes have been geared to preparing the rural villager and the health delivery team- the two essential components of PHC--to work together to identify and solve problems. Too often health workers fear that the unrealistic expectations of community members will mean losing control of scarce resources. Clearly, central to any PHC programme is deciding where and how to begin developing the trust and interaction necessary to implement PHC beyound its curative aspects. In East New Britain, Papua New Guinea, nurses were the logical resource to reorient the rural health extension changeover to the noncurative aspects of PHC. Below, a report on this successful project. PMID- 2312243 TI - Community nursing in The Netherlands. AB - Major developments and changes are currently taking place in the Dutch health care system and community nurses are reacting now to assure they have their proper place in the future setup. Community nurses in other Western countries can perhaps find new ways to contribute to their national health schemes by following their example. PMID- 2312244 TI - Paris declaration on women, children and AIDS. PMID- 2312245 TI - Colonic transit in spinal cord-injured patients. AB - This report describes a study of transit time through the colon, as well as the caliber of the colon and distal small bowel, in 28 spinal cord-injured patients to see if there is a correlation between those findings and difficulty with bowel care and symptoms. In 15 of these 28 patients anorectal dynamic studies were also done. Each patient ingested 20 radiopaque markers, after which colon transit times were measured by multiple abdominal radiographs. The width of the ileum was measured and correlated with symptoms. The findings indicate that transit time was delayed in the left and rectosigmoid colon; four patients had a large and highly compliant rectum, whereas six had anorectal dyssynergia. All ten had difficulty with bowel care. The distal small bowel was dilated in ten patients, all of whom had symptoms and nine of whom had spinal cord lesions superior to T5. PMID- 2312246 TI - Magnetic starch microspheres, efficacy and elimination. A new organ-specific contrast agent for magnetic resonance imaging. AB - A new particulate magnetic resonance (MR) contrast agent was prepared by controlled precipitation of iron oxide in an aqueous starch solution. The potential of the magnetic starch microspheres (MSM) as a hepatosplenic contrast enhancer was studied by MR spectroscopy and MR imaging. Intravascular administration of MSM to rodents showed an effective blood clearance and a tissue specific localization of the substance. MSM doses in a range of 0.3-1.5 mg Fe/kg caused a 50% alteration in sensitive contrast parameters (ED50 doses) of liver and spleen. The contrast effect of MSM in liver and spleen was halved within 2 to 5 days. The approximated lethal MSM dose in mice was 150-200 mg Fe/kg. MSM is a tissue-specific MR contrast substance with high efficacy, rapid bioelimination, and low acute toxicity. PMID- 2312247 TI - Effects of angiographic contrast media on venous endothelium of rabbits. AB - The effects of ionic and nonionic contrast media on rabbit venous endothelium were examined. In anesthetized animals, caudal mesenteric veins were exposed and perfused with the ionic contrast medium, diatrizoate, and the nonionic contrast media iopromide and iotrolan for 2 minutes at 5 mL/minute. Control animals were similarly perfused with physiologic saline or a 23% sorbitol solution. The specimens were fixed in situ by perfusing 4% glutaraldehyde, and ultrathin stained sections were examined with an electron microscope. The hyperosmolar contrast medium diatrizoate produced shrinkage in cell cytoplasm and in nuclear material. There also were minor structural alterations in endoplasmic reticulum and widening of intercellular junctions. The nonionic contrast media iotrolan and iopromide caused mild to moderate changes in endothelial cells. Sorbitol infusion, however, affected venous endothelium more intensely than the ionic and nonionic contrast media, suggesting hyperosmolality as the causal factor in endothelial damage. PMID- 2312248 TI - Low osmolality contrast media and metabolic changes in the myocardium during free and reduced coronary flow in the dog. AB - The authors assessed whether intracoronary injection of low osmolality contrast media induces metabolic and electrocardiographic changes consistent with myocardial ischemia in anesthetized dogs. Ioxaglate and iohexol were injected into the left main coronary artery (eight dogs) and into a carotid-coronary artery shunt (eight dogs), during free coronary flow and during 50% flow reduction. Blood samples were obtained simultaneously from a femoral artery and from a small cardiac vein draining the contrast perfused area. Contrast media had no immediate or late effects on lactate balance during free or reduced flow. Early depression of the ST segment in epicardial ECG did not reflect ischemia. The authors conclude that the two low-osmolality contrast media, iohexol and ioxaglate, did not induce ischemic changes in the myocardium. PMID- 2312250 TI - Iopamidol as a gastrointestinal contrast agent. Lack of peritoneal reactivity. AB - The ideal contrast agent in patients suspected of having gastrointestinal perforation is an iso-osmolar, or nearly iso-osmolar substance, that causes no peritoneal reaction. Iopamidol is a nonionic water-soluble contrast medium that may be considered in such situations. Intraperitoneal injections of ionic and nonionic contrast agents were compared in rats to study potentially harmful peritoneal inflammation. Only intraperitoneal barium injection produced any significant tissue reaction, such as adhesions and ascites. There was no difference between iopamidol and the other water-soluble contrast agents. Iopamidol may satisfy the need for nonreactive and nearly iso-osmolar contrast agents for evaluating patients with possible bowel perforation. However, the high cost of this agent may make its clinical application impractical. PMID- 2312249 TI - Satisfaction of search in diagnostic radiology. AB - A subset of underreading errors (false-negative responses) in radiology has been attributed to "satisfaction of search," which occurs when lesions remain undetected after detection of an initial lesion. This phenomenon has not been studied in the experimental laboratory. A primary goal of this study was to develop a procedure or paradigm to study satisfaction of search. The authors measured detection accuracy for native lesions in images before and after the addition of a simulated nodular lesion. Simulated and native lesions were not spatially superimposed and the native abnormalities were physically identical with and without the nodules. Only responses related to the native lesion were analyzed. Accuracy parameters of receiver operating characteristic (ROC) curves were estimated by the method of maximum likelihood and jackknife. The average perceptual accuracy of the individual ROC curves as measured by Az and de' was significantly reduced with addition of the nodules (t = 2.364, p = 0.025, t = 2.648, p = 0.017, respectively). Az and de' parameters of the pooled ROC curve showed a similar effect (t = 1.573, p = 0.080; t = 1.934, p = 0.047, respectively). The results indicated a substantial satisfaction-of-search effect, with diminished accuracy in perception of native lesions. PMID- 2312251 TI - Experimental gallstone dissolution with methyl-tert-butyl ether (MTBE) and transcutaneous ultrasound energy. AB - The simultaneous application of ultrasound energy greatly accelerated the rate of cholesterol gallstone dissolution by methyl-tert-butyl ether (MTBE). In vitro experiments using this treatment showed that a 498-mg stone burden could be dissolved in 19.5 minutes, approximately 100% faster than what could be achieved with MTBE alone. Pigs (n = 13) with surgically implanted gallstones were treated with MTBE and transcutaneously applied ultrasound from a prototype system built for clinical studies. The average stone reduction of all pigs was 470.46 mg +/- 60.44 mg; 91.39% of an average implanted burden of 515.08 +/- 18.03 mg. Control group pigs (n = 9), receiving only an MTBE infusion, showed an average stone reduction of 51.77%. Enzymes indicative of hepatocellular injury showed no significant abnormalities after 6 weeks. Gallbladder ablation with a fibrous remnant (ie, no mucosa, no lumen, patent cystic duct) occurred in 10 (70%) of the pigs. PMID- 2312252 TI - Magnetic susceptibility effects of trabecular bone on magnetic resonance imaging of bone marrow. AB - High-field spectroscopic studies at 5.88 tesla (T) indicate significant T2* shortening of water in suspensions of powdered bone, interpreted to be a result of magnetic susceptibility differences between bone particles and water. The authors investigated the effects of magnetic susceptibility differences between trabecular bone and water on magnetic resonance (MR) images at 0.6 T. The phantom was constructed of macerated intact trabecular human bone immersed in water. Although susceptibility-induced magnetic field inhomogeneities were detected by spectral line broadening by using an asymmetric spin-echo technique, the results show only a modest T2* shortening at this field strength. As expected, no T1 effect of trabecular bone was observed. Although susceptibility effects of trabecular bone may have a small impact on the signal intensity of MR images of bone marrow at midfield strength, the observed field strength dependence of these effects would predict significant susceptibility effects on clinical images at higher field strength. PMID- 2312254 TI - Topographic representation of the pharyngoesophageal segment during swallowing. AB - Motility of the pharyngoesophageal segment (PES) was monitored by cineradiography (50 frames a second) during barium swallow and analyzed by a computerized topographic mapping of sagittal wall motion. Through measurement of wall displacement on 20 consecutive levels of the PES, distention, contraction, and peristalsis were studied. Topographic mapping of three patients with normal PES motility, delayed opening of the cricopharyngeus, and incomplete opening of the cricopharyngeus, was performed. These topographic mappings show that "narrowing" at the level of the cricopharyngeus reflects expansion of the hypopharynx and cervical esophagus around the cricopharyngeus, rather than a true narrowing. In addition, analysis of wall motion demonstrated that abnormality of the circopharyngeus is often associated with abnormality of wall motion in the adjoining hypopharynx and cervical esophagus. Thus, topographic mapping of the cricopharyngeus is of value because it enables detailed analysis of wall motion during various pathologic conditions. PMID- 2312253 TI - The effect of intra-articular gadolinium-DTPA on synovial membrane and cartilage. AB - This investigation evaluated the potential effect of gadolinium (Gd)-DTPA dimeglumine on synovial membrane and joint cartilage, using macroscopic, microscopic, and x-ray fluorescent spectroscopic techniques. Thirteen New Zealand white rabbits (26 knees) were used in this study, ten receiving 500 micromolar injections of Gd-DTPA-dimeglumine in their right knees; the remainder of the knees served as controls. One injected knee had minimal joint effusion and one had mild hyperemia. Microscopically four knees exhibited mild focal hyperplasia of the synovium, another three minimal focal mononuclear cell infiltration. X-ray fluorescent spectroscopy demonstrated no evidence of Gd-DTPA-dimeglumine in the synovium or articular cartilage. Neither macroscopic nor microscopic evaluation detected any Gd-DTPA-dimeglumine related effects. Gd-DTPA-dimeglumine was found to be safe for intra-articular injection in this animal model. PMID- 2312255 TI - Effect of on-site facilities on use of diagnostic radiology by non-radiologists. AB - This study uses self-reports from a nationwide sample of 5447 physicians in ten medical and surgical specialties to assess the impact of on-site facilities on the use of radiologic examinations by non-radiologists. Data from 169,559 patient visits show that when on-site radiologic facilities are available to non radiologists, radiographs increase by a factor of 1.2 (internal medicine) to 1.7 (pediatrics). Use of radiologic examinations is up to four times greater for hospitalized compared with nonhospitalized patients and is slightly higher for hospital-based physicians and for younger physicians. PMID- 2312256 TI - Academic radiology, turf conflict and antitrust laws. PMID- 2312258 TI - Cases from A3CR2. Migratory chest mass. PMID- 2312257 TI - Cystic pelvic mass in a patient having recurrent carcinoma of the cervix. AB - The diagnostic difficulties encountered with atypical tumor growth are reported in a 29-year-old female with recurrent carcinoma of the uterine cervix. Following a Wertheim-Meigs procedure and resection of local tumor recurrence eight months later, a second recurrence was detected on CT as a purely cystic lesion in the left pelvic wall. Although the size of the cyst subsequently increased, the patient remained asymptomatic until slight pain developed in the left leg 28 months after initial therapy. One month later, limping was noticed; plain radiography showed a large osteolytic lesion of the left hip and on I.V.U., a dilatation of the left renal collecting system was observed. Pelvic CT showed only minimal solid tissue components within a large cyst. Multiple needle aspirations of the cyst and cytological examinations of the fluid obtained showed no evidence of tumor cells. A definitive histological diagnosis of metastasizing squamous cell carcinoma was only reached after surgery. PMID- 2312259 TI - Determination of surface bound and shed HLA antigens of amniotic cells by ELISA. AB - HLA typing of amniotic cells for clinical purposes using the conventional cytotoxicity assay is a laborious and complicated procedure. In the present study we demonstrate that HLA class I typing of the fetus can be determined using the enzyme linked immunosorbent assay (ELISA) either on amniotic cells or soluble free antigens shed by the cells into the culture medium. Our results indicate that the ELISA technique is a sensitive and reliable assay that can be used as an alternative method of HLA class I typing of amniotic cells. PMID- 2312260 TI - Bilateral posterior glenohumeral fracture-dislocation: CT appearance. PMID- 2312261 TI - Fooling with mother nature. PMID- 2312262 TI - Nursing, ethics, & professional roles. PMID- 2312263 TI - Just what does Webster mean? PMID- 2312264 TI - Genetics and human malleability. PMID- 2312265 TI - Organ transplantation: a paradigm of medical progress. PMID- 2312266 TI - Modernizing mortality: medical progress and the good society. PMID- 2312267 TI - Let's take Baby Doe to Alaska. PMID- 2312268 TI - Live sperm, dead bodies. PMID- 2312269 TI - Nancy Beth Cruzan: in no voice at all. PMID- 2312270 TI - The report: many voices in conversation. PMID- 2312271 TI - The calculus of consent. PMID- 2312272 TI - Can others exercise an incapacitated patient's right to die? PMID- 2312273 TI - Practicing ethics: where's the action? PMID- 2312274 TI - Uncertainty, accountability, & HIV-infected physicians. PMID- 2312275 TI - Computed tomography of the clinically negative neck. AB - Members of the New York Head and Neck Society conducted a multi-institutional review correlating preoperative computed tomography (CT) of the neck with postoperative pathology in 59 patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx, without palpable lymphadenopathy. All underwent CT followed by surgery that included partial or complete cervical lymphadenectomy. Sixteen (28%) patients had occult cervical metastases including 6 (17%) of 36 patients with "early stage" (T1 and T2) primary tumors and 10 (44%) of 23 patients with "advanced" (T3 or T4) lesions. There was agreement of CT scan findings with presence or absence of metastatic disease in 41 (69%) of 59 studies, with sensitivity 38%, and with specificity 81%. Findings of central lucency and nodal confluence were highly reliable indicators of malignancy, whereas nodal size bore a less direct relationship. Intravenous contrast medium was useful for anatomical delineation, but not for identification of malignancy. Review of films by a single radiologist did not produce greater diagnostic accuracy than the original interpretations. The authors conclude that while it is not possible to identify all instances of cervical node involvement, employment of CT in addition to physical examination and prognostication based on primary tumor stage will facilitate appropriate selection of patients for elective treatment of the neck. PMID- 2312276 TI - Thyroid carcinoma presenting as a regional neck mass. AB - During 1978-1988, we treated 197 patients with thyroid carcinoma. Twenty-seven patients (14.0%) presented with a regional cervical mass and a clinically normal thyroid gland on initial evaluation. Excisional biopsy proved the diagnosis of metastatic thyroid carcinoma in every patient. Subsequent thyroid scans were 42% sensitive. Only 3 patients underwent fine-needle aspirations; none showed evidence of malignant cells. Review of surgical specimens showed total involvement of the gland in 13 of 17 cases, with extracapsular spread of tumor in 3 patients. Multicentric disease was present in all but 2 neck specimens. Patient follow-up from 1 month to 10 years revealed an 11.5% recurrence rate. The results in this group of patients is compared to the larger group of thyroid carcinoma patients, where three recurrences were found in 170 patients presenting with a clinically palpable mass in the thyroid gland. Analysis of our population comparing the subgroup with the larger series of thyroid carcinoma patients suggests that thyroid carcinoma presenting as a regional neck mass is a more aggressive disease. PMID- 2312277 TI - Free jejunal interposition graft for reconstruction of the esophagus. AB - Forty-seven patients underwent pharyngoesophageal reconstruction using a free jejunal interposition graft (FJIG) at Duke University Medical Center from 1978 through 1987. There were 30 men and 17 women with ages ranging from 38 to 87 years old (mean age, 64 years). Twenty-one patients (group A) had no prior surgical procedures, 20 (group B) were reconstructed following radiation and/or surgical failure, with 6 patients (group C) having benign strictures of the upper alimentary tract. Follow-up ranged up to 122 months (mean, 23 months), with 3 patients lost to follow-up, and 4 perioperative deaths (within 3 months of surgery). There were a total of 9 initial graft failures, 4 patients undergoing successful re-implantation, resulting in an overall success rate of 89% (42 of 47). Excluding patients with graft failures, perioperative deaths, and patients lost to follow-up, 33 of 36 patients with a viable FJIG were able to maintain adequate swallowing function yielding a physiologic success rate of 86%. All of the 21 patients dying of recurrent disease had excellent palliation with the FJIG. Of the 7 patients who are alive, only 1 has dysphagia secondary to stricture. In conclusion, it is felt that the FJIG is a sophisticated method of reconstructing large surgical defects of the pharyngoesophagus with a high technical and physiologic success rate. PMID- 2312278 TI - Modification of compensatory swallowing in a supraglottic laryngectomy patient. AB - Results are presented for repeated videofluoroscopic and scintigraphic examinations of a supraglottic laryngectomy patient, illustrating the successful use and later changes in a compensatory swallow. Issues in patient management are outlined, stressing the importance of interaction between radiologists and dysphagia therapists in the rehabilitation of such patients. PMID- 2312279 TI - Risk of wound infection in patients with head and neck cancer. AB - The purpose of this analysis was to determine the most important factors contributing to operative wound infections for patients with head and neck cancer. Four hundred cases were studied prospectively at M. D. Anderson Cancer Center within an 18-month interval. Potential risk factors were categorized based on the patient, the disease, and the treatment. Sixty-three (19.75%) wound infections were recorded. Univariate analysis identified the following factors to significantly alter the incidence of the infection: nutritional status and alcohol consumption (patient factors); T stage and N stage (disease factors); and duration of surgery, type of surgical wound, complexity of the procedure, use of flaps, blood replacement and the use of drains, nasogastric tubes, and tracheostomies (treatment factors). A logistic regression analysis identified the type of surgery, the choice of antibiotic, the presence of concomitant disease, and the N stage to represent the combination of factors most predictive of infection. The initial step toward preventing surgical wound infection is to identify the high-risk factors. The results of this study help to define these parameters so that specific measures can be taken to counteract wound infection. PMID- 2312280 TI - Early gold weight lid implant for rehabilitation of faulty eyelid closure with facial paralysis: an alternative to tarsorrhaphy. AB - Although tarsorrhaphy has been the mainstay of treatment for lagophthalmus associated with facial paralysis, it has many drawbacks which make it a less than ideal procedure. Gold weight implantation is a functionally and cosmetically superior alternative in many patients. Eighteen patients with both reversible and irreversible facial (eyelid) paralysis underwent early gold weight implantation for rehabilitation of faulty eyelid closure with satisfactory results. The advantages and disadvantages of this technique, when compared with other methods of correcting paralytic lagophthalmus, are discussed. PMID- 2312281 TI - Intraosseous frontal hemangioma. AB - Intrasosseous hemangioma is a rare vascular malformation of bone infrequently described in the otolaryngologic literature. We report a case of this unusual tumor involving the frontal bone. Bone scan, computed tomographic (CT) scan, and histologic findings are illustrated. Differential diagnosis includes meningioma, eosinophilic granuloma, metastatic carcinoma, and other bony lesions. Treatment is complete surgical excision. PMID- 2312282 TI - Intramuscular hemangioma of the sternomastoid muscle. AB - Intramuscular hemangiomas of head and neck are uncommon benign tumors. They arise most frequently in the masseter muscle and may present a diagnostic problem. The clinical presentation is usually that of a slowly enlarging intramuscular mass. The recurrence rate is high following enucleation. A case of a rapidly evolving sternomastoid hemangioma is described which presented in unusual circumstances. The angiographic appearances of this tumor were diagnostic, and the lesion was subsequently resected completely together with a cuff or normal muscle. PMID- 2312283 TI - Spontaneous and nonspontaneous internal jugular vein thrombosis. AB - Nonspontaneous internal jugular vein thrombosis (IJVT) is an uncommon condition historically associated with deep neck infections during the pre-antibiotic era. Today, trauma to the internal jugular vein from catheterization and repeated intravenous injections by drug users are the leading causes of thrombosis, with direct extension of tumor being a rare cause. Spontaneous IJVT occurs when there are no apparent predisposing causes, although many of these patients may harbor an occult malignant neoplasm. Therefore, careful investigation and follow-up are imperative in these patients. The diagnosis of IJVT is readily confirmed by contrast-enhanced computed tomography or magnetic resonance imaging. Management of IJVT involves anticoagulation, antibiotics, and with few indications for surgical intervention. PMID- 2312284 TI - Metastatic squamous cell carcinoma of the parotid: a case of an occult primary. AB - Metastatic squamous cell carcinoma involving an intraparotid lymph node, although uncommon, remains of practical consideration in the differential diagnosis of a parotid mass. This is of particular importance when the primary skin lesion is not readily identifiable, or has been inadequately managed in the past. A representative case is presented, and a review of the literature follows with special emphasis on the anatomy of the parotid lymphatics and the implications for appropriate treatment. PMID- 2312285 TI - Dermatofibrosarcoma protuberans. AB - The consultants agreed that dermatofibrosarcoma protuberans is characterized by its persistent growth and locally aggressive behavior. However, they did not all agree on the mode of treatment. Drs. Schuller and Snyderman favored surgical resection of the involved areas including the right cheek, lower eyelid, and any necessary portions of the nasal ala and upper lip. They encouraged the use of Moh's chemosurgery to detect microscopic disease. They were also in agreement regarding reconstruction, suggesting a cervical-facial or bi-lobed flap for the cheek. A full-thickness skin graft was recommended for the lower eyelid with primary closure planned for the lip defect. They disagreed on the use of postoperative radiation therapy. Dr. Schuller elected not to irradiate; Dr. Snyderman favored 60 to 65 Gy post-operatively. Dr. Quivey expressed concern regarding the morbidity from such a large resection and extensive reconstruction and suggested primary radiation therapy with external beam. All three consultants felt that good follow-up would include thorough head and neck examinations with MRI and/or CT scans if there were any concern about tumor recurrence. PMID- 2312286 TI - Ethical dilemmas in head and neck cancer. PMID- 2312287 TI - [The value of fine-needle aspiration cytology in the after-care of malignant melanoma]. AB - In recent years, we have carried out 146 fine-needle aspiration cytologies (FNAC) for diagnostic clarification of putative metastases from melanomas. The cytodiagnostic appraisal was based on general criteria for the malignancy of tumour cells as well as on particular melanoma-specific findings. Different cell variants can be differentiated in cytological terms. Validation of the cytological diagnoses was possible in 118 of the 123 evaluable FNAC, either by histological examination of the subsequently excised lesions or on the basis of the further clinical progress observed. Statistical evaluation revealed a sensitivity of 93.8% for this method and a specificity of 100%. In our experience, FNAC is thus a diagnostic method that is of great value in the rapid and reliable diagnosis of suspected metastatic lesions in the clinical follow-up of melanoma patients. PMID- 2312288 TI - [Differential response of head and beard hair to gestagens]. PMID- 2312289 TI - The 1986 and 1988 UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) reports: findings and implications. AB - The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has published a substantive series of reports concerning sources, effects, and risks of ionizing radiation. This article summarizes the highlights and conclusions from the most recent 1986 and 1988 reports. The present annual per person effective dose equivalent for the world's population is about 3 mSv. The majority of this (2.4 mSv) comes from natural background, and 0.4 to 1 mSv is from medical exposures. Other sources contribute less than 0.02 mSv annually. The worldwide collective effective dose equivalent annually is between 13 and 16 million person-Sv. The Committee assessed the collective effective dose equivalent to the population of the northern hemisphere from the reactor accident at Chernobyl and concluded that this is about 600,000 person-Sv. The Committee also reviewed risk estimates for radiation carcinogenesis which included the new Japanese dosimetry at Hiroshima and Nagasaki. These data indicate that risk coefficient estimates for high doses and high dose rate low-LET radiation in the Japanese population are approximately 3-10% Sv-1, depending on the projection model utilized. The Committee also indicated that, in calculation of such risks at low doses and low dose rates, a risk-reduction factor in the range of 2-10 may be considered. PMID- 2312290 TI - Trends in radiation protection of medical workers. AB - Medical workers constitute the largest group of individuals occupationally exposed to radiation, and their collective dose equivalent is exceeded only by persons employed in the nuclear fuel cycle. Although medical workers have increased in number by about 50% over the past two decades, their collective dose has steadily declined. Factors that contribute to changes in the exposure patterns of medical workers include variations in demand for medical imaging procedures, changes in the way these procedures are administered to patients, and development of devices that utilize radiation more efficiently and display radiation-derived information more effectively. Trends such as the movement of imaging procedures into nonradiologic disciplines and nonhospital settings, and the imposition of economic and legal considerations into decisions about patient management and health care, may also ultimately affect the exposure of medical workers to radiation. PMID- 2312291 TI - Activation of Co released by in-core and ex-core sources. AB - A methodology was developed for explicitly calculating the amount of 60Co generated in a neutron flux given release rates of 59Co from both in-core and ex core sources. The approach permits calculation of an enhancement factor which is a measure of the larger 60Co inventory that arises when the two types of sources release 59Co at the same rate. The enhancement factor depends significantly on the value chosen as the core residence time for 59Co released from ex-core sources. PMID- 2312292 TI - Examination of the impact of radioactive liquid effluent releases from the Rancho Seco Nuclear Power Plant. AB - A project has been carried out by Oak Ridge National Laboratory (ORNL) to estimate the concentrations of radionuclides in the environment resulting from the release of radioactive materials in the liquid waste effluents from the Rancho Seco Nuclear Power Plant (RSNPP) and to estimate possible radiation doses to man resulting from current environmental concentrations. To accomplish the objectives of this project, ORNL staff members conducted an environmental sampling program around the plant site during November and December 1984. Elevated levels of some anthropogenic radionuclides were found in the immediate environment of the plant. This radioactive contamination occurs primarily along streams receiving effluent from the plant and in fields irrigated with water from these streams. The primary contaminants are 137Cs and 134Cs, with lesser amounts of 60Co and 58Co. The ingestion of fish was the single most important pathway identified in this analysis. However, all specific pathways of exposure and usage factors were not precisely known for a complete dose assessment of current and potential use of contaminated water and soil around the RSNPP. The liquid effluent radionuclide releases from the RSNPP pose no significant health hazard to persons living near the RSNPP. PMID- 2312293 TI - Performance evaluation of continuous air monitor (CAM) sampling heads. AB - Continuous air monitor (CAM) samplers are used to detect radioactive aerosol particles in nuclear facilities and to provide alarm signals should the concentrations exceed a multiple of the derived air concentration (DAC) of the radionuclide of concern in a set amount of time. Aerosol particles are drawn into a CAM sampler where collection is to take place upon a filter. Radioactivity of the particles is determined with a detector that is placed in close proximity to the filter face. An important determinant of CAM performance is the ability of the inlet and body of the CAM to transport particulate matter in the inhalable size range (less than or equal to 10 microns aerodynamic diameter) to the filter without substantial loss or bias with respect to particulate size. Three types of CAM samplers were tested in a low-velocity aerosol wind tunnel to determine the degree to which particles penetrate through the flow systems to the collection filter under conditions typical of normal room air exchange rates. Two air velocities were used: 0.3 and 1.0 m s-1. The CAM samplers were primarily operated at a flow rate of 56.6 L min-1, although some tests were conducted at a flow rate of 28.3 L min-1. The CAM units were prototypes manufactured by Kurz Instruments, Eberline Instrument Corporation, and Victoreen Inc. These three units represent three different approaches to CAM head design. At an air speed of 1 m s-1, aerosol penetration to the filters of the Kurz unit was essentially 100% for particle sizes of 3 and 7-microns aerodynamic diameter and was 86% for a size of 15 microns. For the Eberline sampler, the penetration was over 80% for 3-microns particles but was reduced to less than 2% for 7-microns particles. The victoreen sampler showed penetration values of 98% for 3-microns aerodynamic diameter particles, 88% for 7-microns particles and 4% for a size of 15 microns. Air speed had little effect on the penetration results for the two speeds which were tested. Tests were conducted to determine the uniformity of deposits on the filters of the CAM samplers. For a particle size of 10 microns, the deposits were nonuniform for all three of the instruments. PMID- 2312294 TI - Dry deposition of 88Rb and 138Cs from a boiling water reactor plume. AB - Double tracer experiments were made in May 1981 at the Ringhals nuclear power plant in Sweden to investigate atmospheric-dispersion and dose models. Sulphurhexafluoride (SF6) and radioactive noble gases were released simultaneously from a 110-m stack and detected downwind at distances of 3-4 km. The experiments were made under near-neutral conditions. One-hour measurements at ground level yielded cross-wind profiles of SF6 concentrations and gamma radiation from the plume. In-situ gamma spectrometric measurements demonstrated a significant surplus of gamma rays from the noble gas daughters (88Rb and 138Cs) compared with those from the noble gases. This surplus was interpreted as due to dry deposition from the plume, and deposition velocities were estimated at 0.02 0.10 m s-1. These values are very high when compared with values recommended for calculating consequences of nuclear accidents. The high values are believed to be due to the very small size of the daughter particles. PMID- 2312295 TI - Bilirubin phototherapy and potential UVR hazards. AB - Bilirubin phototherapy is a treatment often used in hospitals to alleviate neonatal jaundice in newborn babies. Phototherapy utilizes blue light and although the phototherapy units emit predominantly in this region, emissions from the adjacent ultraviolet region present a possible hazard if the exposure is of sufficient duration. A study of the levels of ultraviolet radiation (UVR) to which patients and staff involved with phototherapy are subjected was therefore undertaken. PMID- 2312296 TI - Ground distribution patterns of selected radioactive, chemical, and physical contaminants from dispersion of U mill tailings. AB - Ground concentrations of 226Ra and total alpha activity as a function of soil depth and distance from an acidic U mill tailings pile were measured, as well as soil pH, sulfate, chloride, and conductivity. Contamination decreased with increasing soil depth and distance from the source. Most of the measured parameters were indistinguishable from background after a distance of 3.3 km from the tailings impoundment. The highest concentrations of all contaminants were contained in the particles less than 0.045 mm in diameter at the soil surface (0 0.6 cm). This fraction represents only 4% to 10% of the total soil mass. Surface soil particles greater than 2.0 mm contained higher concentrations of all contaminants than the intermediate-size (0.045-2.0 mm) fraction. Aggregate formation of the greater than 2.0-mm fraction from small particles or preferential erosion and transport of the tailings sand fractions were proposed as possible explanations. The significant correlations between various measurements were soil 226Ra vs. total alpha activity, sulfate concentration, and conductivity. The latter two parameters are indicative of sulfuric acid leached tailings. The sulfate concentration appeared to be a sensitive and easily measured indicator of tailings contamination and migration into the soil profile. Furthermore, sulfate may be used to delineate acidic U tailings from other sources of contamination (U ore dust, yellowcake, naturally elevated U and Ra) in the environment. Actual site measurements for surface 226Ra concentration were approximately twice the MILDOS computer code prediction. PMID- 2312298 TI - Ethical aspects of nuclear waste. PMID- 2312297 TI - A proposed multi-detector method for prompt 90Sr detection in post-accident environmental matrices. AB - Strontium-90 is of relevant biological importance among fission products released during a fission reactor accident. Rapid information on its concentration in environmental matrices is extremely valuable, yet this implies chemical separations and handling with a shift in daughter equilibrium and therefore the need to wait a sufficient time for the equilibrium to be reestablished. The work concerns a feasibility study of a multi-detector system for a prompt evaluation of the 90Sr activity or, at least, a prompt determination of its order of magnitude in the presence of other pure beta and beta-gamma emitters; their interferences are examined on the basis of the Chernobyl releases and their decay properties. The technique is based on a plastic scintillator beta detector and a guard ring of BGO counters which can be logically connected in coincidence and anticoincidence. The evaluations show that a few hours are sufficient to determine a specific activity comparable with the Maximum Permissible Concentration in air by sampling 10 m3. PMID- 2312299 TI - Volatility of 35S. PMID- 2312300 TI - The dose rate effectiveness factor. PMID- 2312301 TI - Transmission of scatter radiation from computed tomography (CT) scanners determined by a Monte Carlo calculation. PMID- 2312302 TI - Indoor 222Rn concentrations over phosphate deposits in North Carolina. PMID- 2312303 TI - Comments on 'An Alternative Method for Ra Determinations in Water'. PMID- 2312304 TI - Rigor of new concepts appearing in ICRU Report No. 39 and No. 43. PMID- 2312305 TI - Micro-area variation in hospital use. AB - Many recent studies have demonstrated that hospital utilization rates vary widely across small geographic areas. The variation is often attributed to the style of practice of the provider. This study demonstrates that hospital utilization varies widely between "micro" areas within individual hospital market areas. Further, the study demonstrates that hospital utilization rates within a hospital market area are more similar to each other than to rates in "micro" areas within other hospital market areas. After adjustment for available demographic, socioeconomic, and epidemiological factors, the utilization rates within "micro" areas are highly related to the group of hospitals that dominates the market area. After simultaneously adjusting for age and poverty, the market share dominant group explains 35 percent of the variance in surgical use rates of "micro" areas and 39 percent of the variance in medical use rates. PMID- 2312306 TI - What is too much variation? The null hypothesis in small-area analysis. AB - A small-area analysis (SAA) in health services research often calculates surgery rates for several small areas, compares the largest rate to the smallest, notes that the difference is large, and attempts to explain this discrepancy as a function of service availability, physician practice styles, or other factors. SAAs are often difficult to interpret because there is little theoretical basis for determining how much variation would be expected under the null hypothesis that all of the small areas have similar underlying surgery rates and that the observed variation is due to chance. We developed a computer program to simulate the distribution of several commonly used descriptive statistics under the null hypothesis, and used it to examine the variability in rates among the counties of the state of Washington. The expected variability when the null hypothesis is true is surprisingly large, and becomes worse for procedures with low incidence, for smaller populations, when there is variability among the populations of the counties, and when readmissions are possible. The characteristics of four descriptive statistics were studied and compared. None was uniformly good, but the chi-square statistic had better performance than the others. When we reanalyzed five journal articles that presented sufficient data, the results were usually statistically significant. Since SAA research today is tending to deal with low-incidence events, smaller populations, and measures where readmissions are possible, more research is needed on the distribution of small-area statistics under the null hypothesis. New standards are proposed for the presentation of SAA results. PMID- 2312307 TI - Patterns of outpatient mental health care over time: some implications for estimates of demand and for benefit design. AB - The article examines patterns of starting and continuing outpatient mental health care as a function of time, and the implications of these patterns for estimates of the response of demand to generosity of fee-for-service insurance coverage. The data are from the RAND Health Insurance Experiment (HIE), which acquired a random sample of the nonelderly general population in six U.S. sites. People rarely had more than one episode of use of outpatient mental health services in a year. Persons who used in the prior year had high rates of continuing in treatment, while those without prior use entered treatment at a low, steady rate. Similar patterns of use by former users and nonusers were observed across insurance plans that varied widely in generosity, but the absolute probabilities of use were significantly lower in less generous plans. The probability of use of mental health services expanded significantly over time in the HIE; thus, estimates of demand in a steady state would be higher than those based on the HIE study years. PMID- 2312308 TI - Quality and provider choice: a multinomial logit-least-squares model with selectivity. AB - A Federal Trade Commission survey of contact lens wearers is used to estimate a multinomial logit-least-squares model of the joint determination of provider choice and quality of care in the contact lens industry. The effect of personal and industry characteristics on a consumer's choice among three types of providers--opticians, ophthalmologists, and optometrists--is estimated via multinomial logit. The regression model of the quality of care has two features that distinguish it from previous work in the area. First, it uses an outcome rather than a structural or process measure of quality. Quality is measured as an index of the presence of seven potentially pathological eye conditions caused by poorly fitted lenses. Second, the model controls for possible selection bias that may arise from the fact that the sample observations on quality are generated by consumers' nonrandom choices of providers. The multinomial logit estimates of provider choice indicate that professional regulations limiting the commercial practices of optometrists shift demand for contact lens services away from optometrists toward ophthalmologists. Further, consumers are more likely to have their lenses fitted by opticians in states that require the licensing of opticians. The regression analysis of variations in quality across provider types shows a strong positive selection bias in the estimate of the quality of care received by consumers of ophthalmologists' services. Failure to control for this selection bias results in an overestimate of the quality of care provided by ophthalmologists. PMID- 2312310 TI - Catherine Burns spreads her wings. Interview by Nick Robin. PMID- 2312309 TI - Uninsured working-age adults: characteristics and consequences. AB - While estimates of the country's uninsured vary, ranging from 10 to 18 percent of the general population, virtually every study on use of medical services reports that lack of health insurance represents a major barrier to medical care. Based on the 1986 national Robert Wood Johnson Access Survey of 10,130 noninstitutionalized persons, the characteristics of working-age adults without health insurance, and the consequences, are examined. Among working-age adults, the uninsured are most likely to be poor or near-poor, Hispanic, young, unmarried and unemployed. Compared with the insured, they have significantly fewer ambulatory visits during a year, are less likely to have contact with a medical provider during a 12-month period, and are more likely to receive their care in a hospital outpatient clinic or emergency room. Differences in health status do not account for these findings. Especially among persons with chronic and serious illnesses, the uninsured are less likely than the insured to receive medical care. Further, the uninsured are significantly more likely to report needing but not receiving medical care, primarily for economic reasons, and although poorer, they have higher out-of-pocket medical expenses than others in the population. PMID- 2312311 TI - Health visiting service suspended. PMID- 2312312 TI - Pulling the plug on the NHS. PMID- 2312313 TI - Health visitors and the Children Act. PMID- 2312314 TI - Assessing the elderly in the community. PMID- 2312315 TI - A different approach to community health care. PMID- 2312316 TI - Distance learning. Helping a return to practice. PMID- 2312317 TI - Setting up a stroke club. PMID- 2312318 TI - Fluoridation: a storm in a reservoir. Interview by Cath Jackson. PMID- 2312319 TI - Women and the NHS bill. A crushing burden of care. AB - The NHS and Community Care bill, if it becomes law, will undermine local health services. Hospitals and health authorities will have no legal obligation to provide even minimum services. Community health is at risk. Women will be the biggest losers. PMID- 2312320 TI - Women and the bill. Cuts threaten women's community psychotherapy service. AB - Shanti, a unique psychotherapy service for women, faces closure as West Lambeth health authority struggles with a massive financial deficit. PMID- 2312321 TI - Job sharing: everyone's flexible friend. AB - More and more health authorities are coming to terms with the idea of less-than full-time working in strategies to solve chronic recruitment and retention problems. PMID- 2312322 TI - Pornography: clearing the shelves. AB - This month sees the culmination of a national campaign against the sale of pornography in high street shops--just one expression of a growing body of public and parliamentary opinion which links pornography and the sexual abuse of women and children. PMID- 2312324 TI - Parents' attitudes to a child clinic. PMID- 2312323 TI - Facilitating a menopause support group. PMID- 2312325 TI - Women's work and working women: childcare and the NHS. PMID- 2312326 TI - Group work--saving a clinic. PMID- 2312327 TI - Infant feeding: the reality gap. PMID- 2312328 TI - Perceptions of the comprehensive-based school nurse. AB - This study was designed by Chris Adams as a pilot for a larger piece of work looking at consumer perceptions of school nurses based in Newcastle comprehensive schools. Although no general conclusions can be drawn from such a small sample the study illustrates the steps taken to carry out the research, the problems encountered and the results obtained from one school--with subsequent discussion. PMID- 2312329 TI - Distance learning: the HVA project's pilot stage. AB - The second article in this series described the origination, aims and early development of distance learning material to help both health visitors who were returning to practice after a number of years, and also those who had stayed in practice but who had little access to courses to update themselves professionally. PMID- 2312330 TI - Health promotion: to market, to market. PMID- 2312331 TI - Benefits update. Part 5 of 5. Mobility allowance in practice. PMID- 2312332 TI - Your rights at work. GP contract. Who's that sitting in your chair? PMID- 2312333 TI - NFPA update: leakage current limits changed. PMID- 2312334 TI - Metron QA5 artifact signal locator. PMID- 2312335 TI - Hemolysis and renal dysfunction associated with autotransfusion. PMID- 2312336 TI - Encore: health devices reprint policy. PMID- 2312337 TI - Bio-Tek products do not have ECRI features. PMID- 2312338 TI - Misconnection of battery cable in Matrx (Ohmeda) first response portable aspirators. PMID- 2312340 TI - Articulated i.v. pole on Lada Optima III birthing beds. PMID- 2312339 TI - Nuclear associates lead-plastic overhead x-ray barriers. PMID- 2312341 TI - Patient error with self-administered enemas. PMID- 2312342 TI - Age structure, environmental fluctuations, and hermaphroditic sex allocation. AB - This paper studies sex allocation in an age-structured population of hermaphrodites living in a temporally fluctuating environment. The general condition for the evolutionary stable state (ESS) of allocation is derived for density-independent dynamics. This condition is used to determine the effect on the deterministic ESS of a dependence of survival rates on allocation. It is also used to identify the special conditions under which a stochastic ESS is given by a product rule and show how demographic structure and the correlation structure of vital rates determines the stochastic ESS. PMID- 2312343 TI - Caithness revisited: Robertsonian chromosome polymorphism in Caithness house mice. AB - The purpose of this communication is to revise and clarify the position regarding house mouse populations with Robertsonian chromosomes in the northern Scottish county of Caithness. PMID- 2312344 TI - Genetic variation in a modifier system affecting the expression of bare mutant of Drosophila subobscura. AB - Genetic variation affecting the expression of Bare (Ba), a morphological mutant of Drosophila subobscura that reduces the number of bristles and is located on the O chromosome of this species, is reported. Our results show that O chromosomes extracted from a natural population (El Pedroso, Santiago de Compostela, Spain) show considerable genetic variation in modifier effect upon Ba expression. The amount of modifier variability is dependent on the chromosomal arrangement (OST and O3 + 4 + 7), since modifier variation is higher in OST than in O3 + 4 + 7 chromosomes. Investigations of the genetic architecture of this modifier system on the O chromosome carried out using biometrical methods indicate that a relatively small number of genetic "factors" can explain the differences in modifier effect between a wild O chromosome of high modifier effect and a marker chromosome of low score. In addition, the modifier effects show a non-uniform distribution along the O chromosome and some indication of clustering of modifier "factors" around the major locus (Ba) is also observed. PMID- 2312345 TI - Cytochemical evidence of NADH-oxidase activity in the isolated working rabbit heart subjected to normothermic global ischaemia. AB - The cytochemical localization of NADH-oxidase, a possible source of oxygen derived toxic species was studied in the isolated working rabbit heart subjected to normothermic global ischaemia. The activity of this oxidase could be important for the damage observed during ischaemia, when cellular defence mechanisms against free radicals are depleted. In non-ischaemic myocardium only small amounts of the NADH-oxidase reaction product were present in the mitochondria. Although the reaction product could already be observed after 45 min of incubation, prolonged incubation times up to 2h were necessary to clearly define these reactive sites. The reaction product is substrate dependent and is not affected by cyanide. Exposure of the hearts to ischaemia resulted in an alteration of the enzyme activity depending on the degree of ischaemic damage. In ultrastructurally slightly altered areas a high degree of activity was observed in the mitochondria. In infarcted tissue, mitochondria contained little or no reaction product. This cytochemical study supports the hypothesis that hydrogen peroxide and oxygen radicals produced in the mitochondria by NADH-oxidase activity may contribute to the mitochondrial damage observed during ischaemia when NADH is no longer oxidized by the respiratory chain and cellular defence mechanisms are impaired. PMID- 2312346 TI - Expression of immunoreactivity for Ca-binding protein, spot 35 in the interstitial cell of the rat pineal organ. AB - In the rat pineal organ numerous stellate cells exhibited intense immunoreactivity for calcium-binding spot 35 protein. Because of their peculiar shape and ultrastructure, identical to those of intrapineal S-100-immunoreactive cells, the spot 35-immunoreactive stellate cells were identified as the interstitial cells. The comparison of the morphology and population density of spot 35-, S-100-, and GFAP (glial fibrillar acidic protein)-immunoreactive cells, suggests that spot 35-immunoreactive cells represent a major subpopulation of the interstitial cells, all of which are S-100-immunoreactive and generally considered to be of glial nature, while GFAP-immunoreactive cells represent a minor subpopulation of the interstitial cells located in the proximal part close to the pineal stalk. This is the first report describing the occurrence of the calcium-binding protein in cells of glial nature. PMID- 2312347 TI - The histochemistry of isocitric and oestradiol-17 beta dehydrogenases in the endometrium of postmenopausal women treated with oestrogens and progestogens. AB - Endometrium was obtained from postmenopausal women during treatment with either oestrogen alone or on the third, sixth, tenth or twelfth day of combined therapy with oestrogens and progestogens. The activities of oestradiol-17 beta and isocitric dehydrogenases were measured in homogenates of the whole tissue and the enzymes were also located histochemically. Oestradiol dehydrogenase was located exclusively within the epithelium, whilst isocitric dehydrogenase was found in both epithelium and stroma, and also in stromal arterioles. Histochemically, oestradiol dehydrogenase was found in all the specimens which exhibited biochemical activity but in none of those from which it was absent. Isocitric dehydrogenase however, was seen in all tissue sections despite widely varying levels of biochemical activity in the homogenate. The method for measuring isocitric dehydrogenase activity was therefore nonspecific, whilst that for oestradiol dehydrogenase was reliable and low levels of enzyme activity could be detected. The latter technique may therefore be useful to predict the sensitivity of endometrial carcinomata to progestogens. PMID- 2312348 TI - Immunocytochemical localization of aromatase in immature rat ovaries treated with PMSG and hCG, and in pregnant rat ovaries. AB - Immunocytochemical localization of aromatase cytochrome P-450 was examined in immature rat ovaries treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG), and in pregnant rat ovaries. It is well known that PMSG and hCG treatments induce ovulation about 12 h after hCG injection. At 24 h after hCG injection, many antral follicles were recognized in immature rat ovaries and only the granulosa cells in the antral follicles were stained weakly with the anti-aromatase antibody. At 0 to 9 h after hCG injection, in addition to the antral follicles, some large Graafian follicles could be observed in the rat ovaries, and the granulosa cells of these follicles were positively stained for aromatase. Each follicle was surrounded by the basal lamina which shows lineally distinct positive reaction against anti-laminin antibody. At 12 h after hCG injection, some large Graafian follicles without oocyte were weakly positive to the anti-aromatase antisera, and the outline of their basal lamina stained with anti-laminin antibody became irregular in shape and fragmentous. At 15 to 18 h after hCG injection, the luteinized cysts could be seen, and the granulosa-lutein cells of these cysts were almost negative for aromatase. Fragmentous reaction to the anti-laminin antibody was observed around the luteinized cysts. In the ovaries of day 4 in pregnancy, only the granulosa cells of the large antral follicles were weakly stained, but corpora lutea negatively reacted to the anti aromatase antibody. At 7 to 19 days in gestation, both the granulosa cells of antral follicles and pregnant luteal cells were positively stained against aromatase antisera.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312349 TI - Effect of tulipin on cell cycle progression analyzed by BrdUrd incorporation. AB - The effect of tulipin, a protein from plant origin recently purified, on cell cycle progression has been analyzed in the sensitive EUE cells by BrdUrd incorporation. The cytofluorimetric results demonstrate that tulipin specifically interacts with the S phase, with a dose-dependent decrease of the total S phase cells and an increase of the G1/G2 cells after 4 h of treatment in the synchronized EUE cells, whereas in the asynchronous population it mainly causes a dose-dependent decrease in the incorporation of BrdUrd per cell. PMID- 2312350 TI - Ultrastructural analysis of estrogen receptor immunoreactive neurons in the medial preoptic area of the female rat brain. AB - Neurons of the medial preoptic area were studied in the brain of the female rat by means of ultrastructural immunocytochemistry using a monoclonal antibody generated against purified estrogen receptor (ER), in order to delineate the morphological correlates of estrogen feedback mechanisms. In addition to the preoptic area, the bed nucleus of the stria terminalis, the arcuate and ventromedial nuclei of the hypothalamus exhibited an intense labelling for estrogen receptor. At the light microscopic level, the cell nuclei were immunoreactive. No major alterations were detected in the ER expression of medial preoptic neurons sampled during the estrous cycle, but proestrous rats did exhibit a slightly increased intensity of staining. At the ultrastructural level, the ER immunoreactivity was primarily confined to the nuclei and associated with the chromatin. Long term steroid deprivation elicited by either ovariectomy or ovariectomy plus adrenalectomy resulted in a marked intensity of nuclear labelling. This pattern was not influenced by acute estradiol replacement. These morphological data indicate that neurons of the medial preoptic area have the capacity to detect estrogens via receptor mechanisms and that changes in the level of the circulating ligand are manifested in an alteration in the staining for the estrogen receptor. The study also supports the revised concept of estrogen receptor action by demonstrating the presence of receptors in the nuclei of the cells, whether or not they are occupied by their ligand. PMID- 2312351 TI - Quantitation of autoradiographic grains in different zones of articular cartilage with image analyzer. AB - A novel method is introduced for the estimation of grain numbers in autoradiographic sections of articular cartilage with an image analyzer. It is based on separation of grains from the underlying structures by gray level thresholding and determination of the percentage of total area occupied by grains in a relatively large measuring field. The mean grain size is used as a reference to calculate grain numbers per cell profile and per unit area of tissue in various zones of bovine articular cartilage labelled with 35S-sulphate in tissue culture. The results demonstrate considerable zonal differences as well as site related topographic variation in the rate of 35S-sulphate incorporation. The largest site-related variation in the grain counts was observed in the superficial zone, suggesting a delicate control of proteoglycan synthesis in this zone. PMID- 2312352 TI - Location of sites of dopamine storage in megakaryocytes by autoradiography. AB - We have used quantitative electron microscope autoradiography to study the subcellular sites of 3H-dopamine uptake in mouse megakaryocytes after a single intraperitoneal injection. Autoradiographic grains were found to be associated almost exclusively with the vesicles of precursors of monoamine-storage organelles. The labeling intensity (radioactivity) of the demarcation membrane system which is continuous with the plasmalemma was also significantly greater than would be expected. On the other hand, radioactivity associated with the remaining sites in the cytoplasm was not significantly different from that expected of a random distribution. In order to compare 3H-dopamine uptake during cell maturation, light microscope autoradiographic studies were also done. Immature megakaryocytes were labeled slightly, but the number of silver grains increased significantly in maturing cells. Mature megakaryocytes were 2.7 times more radioactive than the maturing cells. Our results suggest that the megakaryocytes were able to accumulate dopamine from the early stages of cell maturation and to store dopamine in precursors of monoamine-storage organelles. PMID- 2312353 TI - Ultrastructural immunocytochemistry and lectin histochemistry of the subcommissural organ in the snake Natrix maura with particular emphasis on its vascular and leptomeningeal projections. AB - The ependymal cells of the subcommissural organ (SCO) of the snake Natrix maura display long basal processes which terminate either on blood vessels or on the leptomeninges. The cell body and the basal processes contain a secretory material detectable immunocytochemically at the light-microscopic level using an antibody raised against bovine Reissner's fiber. The present investigation deals with the ultrastructural location in these cells of the (i) immunoreactive material; (ii) concanavalin A (Con A)- and wheat-germ agglutinin (WGA)-binding sites. In the subnuclear region the immunoreactive material was located within dilated cisternae of the rough endoplasmic reticulum and had affinity for Con A but not for WGA. In the supranuclear region the secretory material was exclusively located within numerous granules. Since all these granules showed affinity for WGA, they can be regarded as "post-Golgi" elements. Thus, at variance with the situation in the mammalian SCO, in the ophidian SCO most of the secretion is stored in secretory granules rather than in dilated cisternae of the rough endoplasmic reticulum. In the perivascular and leptomeningeal endings the immunoreactive material was located within granules which, because of their affinity for WGA, should also be regarded as true secretory granules derived from the Golgi apparatus. It is concluded that these granules are transported along the basal processes and accumulated in the perivascular and leptomeningeal endfeet. This observation favours the view of a local release of the content of these granules, since there is no evidence for a reverse transport of these granules all the way back from the distal termination to the apical pole, to be finally released into the ventricle. PMID- 2312354 TI - The fine structural localization of endogenous and exogenous peroxidase activity in human bone marrow mast cells under pathological conditions. AB - We have examined the ultrastructural characteristics of peroxidase activity in human bone marrow mast cells. These studies were performed in three patients with systemic mast cell disease, and in another six patients showing bone marrow mast cell hyperplasia. Endogenous peroxidase activity was localized in the perinuclear cisternae and strands of endoplasmic reticulum, but never in the granules. We have also demonstrated the "in vivo" existence of exogenous peroxidase activity in two of the three cases of systemic mast cell disease. The peroxidase internalization involved its binding to the plasma membrane, followed by its incorporation into the cell by a general endocytic process comprising the uptake of dispersed peroxidase-positive material mainly by phagocytosis of granular structures containing peroxidase. The exogenous peroxidase appeared in non membrane bound granules, vacuoles or aggregates, but we have never seen the enzyme linked to the mast cell granules. PMID- 2312356 TI - Microphotometric determination of enzymes in brain sections. I. Hexokinase. AB - A histochemical procedure was established for the microphotometric determination of hexokinase (HK) in sections of the rat hippocampus, which served as an exemplary brain region. For this quantitative procedure, slides were coated with glucose 6-phosphate dehydrogenase (G6PDH) as an auxiliary enzyme and sections were mounted onto this enzyme film. The sections were then incubated with the following adapted incubation medium: 5 mM D-glucose, 1.5 mM NADP, 7.5 mM ATP, 4 mM nitroblue tetrazolium chloride, 10 mM NaN3, 10 mM MgCl2, 0.25 mM phenazine methosulfate, 1 U/ml G6PDH, 22% polyvinyl alcohol in 0.05 M Hepes buffer; the final pH was 7.5. A linear response of the reaction was observed in the initial 10 min of reaction (kinetic and end-point measurements). The relationship between HK activity and section thickness was linear up to 5 microns. The need for such thin sections is discussed in relation to the limited penetration of the auxiliary enzyme into the section. It is concluded that the quantitative demonstration of HK in brain sections could be a valuable tool for studying the local metabolic entrance of glucose in the glycolytic pathway. PMID- 2312355 TI - Peroxisomes of the rat cardiac and soleus muscles increase after starvation. A biochemical and immunocytochemical study. AB - We have investigated the change of catalase activity in the homogenates of rat cardiac and skeletal muscles. After 7 days' starvation, the catalase activity of heart increased about 3-fold and that of soleus muscle enhanced 2-fold higher than that of control rats. Immunoblot analysis of catalase showed a single band in the homogenates of cardiac and soleus muscles and increase of catalase antigen after starvation. Light microscopic immunoenzyme staining showed that after starvation catalase positive granules markedly increased in both the cardiac and soleus muscle. Quantitative analysis of the staining showed that number of the granules per 100 microns 2 of tissue section was about 1.4-fold in the soleus muscle and 1.7-fold in the cardiac muscle after starvation. By electron microscopy of alkaline DAB staining, we confirmed that the granules were peroxisomes, which increased in both number and size. Furthermore, we stained the peroxisomes for catalase by a protein A-gold technique. Labeling density (gold particles/micron 2) of the cardiac and soleus muscles from the starved rat increased approximately 1.4 times as much as that of normal animal. When the numerical density is multiplied by the labeling density, the values are largely consistent with the enhancement of catalase activity. These results show that increase in the catalase activity of the muscle tissue after starvation is caused by increase in number and size of peroxisomes. PMID- 2312357 TI - Immunocytochemical detection of prolactin or prolactin-like immunoreactivity in epididymis of mature male mouse. AB - Prolactin (PRL) binds to the testis of mice and rats where it increases the number of luteinizing hormone receptors, increases the binding of human chorionic gonadotropin (hCG) to LH receptors, and enhances testosterone synthesis and secretion. PRL also binds to the prostate and seminal vesicles of rats and humans where it increases organ weight and stimulates growth and uptake of testosterone. PRL binds to the epididymis of rats but the effect of PRL on this organ is unknown. In the present study, a standard immunoperoxidase (PAP) technique was used to detect the binding of endogenous and exogenous PRL or PRL-like peptides to the epididymis of the mature mouse. Throughout the epididymal duct, a positive reaction for peroxidase, suggesting PRL or PRL-like binding, occurred in the Golgi area of principal cells. In segment 1, positive reactions were also visualized in the perinuclear area and in the region located between the Golgi area and the apical surface of the principal cells (supra-Golgi area). In the corpus and cauda epididymidis, scattered entire principal cells were also positive. Throughout the epididymal duct, the reactions indicating the binding of exogenous PRL were slightly stronger than those testing for binding of endogenous peptides. The significance of such binding to the epididymis is uncertain but PRL may perform the same functions in epididymal principal cells as it does in the testis, prostate, and seminal vesicles. PMID- 2312358 TI - Ultrastructural and cytochemical studies of nucleolus-like bodies in neurons of rat sympathetic ganglia. AB - Intracytoplasmic fibrillar inclusions, generally referred to as nucleolus-like bodies (NLBs) were studied by means of ultrastructural cytochemistry. The structure of these bodies was visualized by several different staining procedures: conventional electron microscopy and preferential staining methods for localization of various proteins including ribonucleoproteins, basic proteins, glycoproteins and phosphorylated proteins. The results of the cytochemical tests indicate that NLBs have an essentially proteinaceous nature. They consist of ribonucleoproteins, basic proteins and glycoproteins but do not contain phosphorylated proteins. These findings suggest that NLBs are, at least partially, of the same nature as nucleoli and coiled bodies. The origin of NLBs and their possible functional role is briefly discussed. PMID- 2312359 TI - Secretory glycoconjugates of a mucin-synthesizing human colonic adenocarcinoma cell line. Analysis using double labeling with lectins. AB - Lectins were used to characterize mucin glycoproteins and other secretory glycoconjugates synthesized by a human colon adenocarcinoma-derived cell line which expresses a goblet cell phenotype. Despite being clonally derived, HT29 18N2 (N2) cells, like normal goblet cells in situ were heterogeneous in their glycosylation of mucin. Only wheat-germ agglutinin, which recognizes N acetylglucosamine and sialic acid residues, and succinylated wheatgerm agglutinin, which binds N-acetylglucosamine, stained the contents of all secretory granules in all N2 goblet cells. The N-acetylgalactosamine binding lectins Dolichos biflorus and Glycine max stained 20% and 21% of N2 goblet cells respectively. Ricinus communis I, a galactose-binding lectin, stained 67% of N2 goblet cells although staining by another galactose-binding lectin, Bandeiraea simplicifolia I, was limited to 19%. Peanut agglutinin, a lectin whose Gal(beta 1 3)GalNAc binding site is not present on mucins produced in the normal colon but which is found on most mucins of cancerous colonic epithelia, stained 68% of the cells. Ulex europeus I, a fucose-binding lectin, did not stain any N2 goblet cells. Four lectins (Lens culinaris, Pisum sativum, Phaseolus vulgaris E, Phaseolus vulgaris L) which recognize sugars normally present only in N-linked oligosaccharides stained up to 38% of N2 goblet cells. The binding of these lectins indicates either both O-linked and N-linked oligosaccharide chains are present on the mucin protein backbone or the co-existence of non-mucin N-linked glycoproteins and O-linked mucins within the goblet cell secretory granule. PMID- 2312360 TI - Glycoconjugate pattern of membranes in the acinar cell of the rat pancreas. AB - Lectin-binding studies were performed at the ultrastructural level to characterize glycoconjugate patterns on membrane systems in pancreatic acinar cells of the rat. Five lectins reacting with different sugar moieties were applied to ultrathin frozen sections: concanavalin A (ConA): glucose, mannose; wheat-germ agglutinin (WGA): N-acetylglucosamine, sialic acid; Ricinus communis agglutinin I (RCA I): galactose; Ulex europaeus agglutinin I (UEA I): L-fucose; soybean agglutinin (SBA): N-acetylgalactosamine). Binding sites of lectins were visualized either by direct conjugation to colloidal gold or by the use of a three-step procedure involving additional immune reactions. The rough endoplasmic reticulum and the nuclear envelope of acinar cells was selectively labelled for ConA. The membranes of the Golgi apparatus bound all lectins applied with an increasing intensity proceeding from the cis- to the trans-Golgi area for SBA, UEA I and WGA. In contrast RCA I selectively labelled the trans-Golgi cisternae. The membranes of condensing vacuoles and zymogen granules were labelled for all lectins used although the density of the label differed between the lectins. In contrast the content of zymogen granules failed to bind SBA and WGA. Lysosomal bodies (membranes and content) revealed binding sites for all lectins used. The plasma membranes were heavily labelled by all lectins except for SBA which showed only a weak binding to the lateral and the apical plasma membrane. These results are in accordance to current biochemical knowledge of the successive steps in the glycosylation of membrane proteins. It could be demonstrated, that the cryo section technique is suitable for the fine structural localisation of surface glycoconjugates of plasma membranes and internal membranes in pancreatic acinar cells using plant lectins. PMID- 2312361 TI - Presence of dopamine-immunoreactive cell bodies in the catecholaminergic group A15 of the sheep brain. AB - Antisera were raised in rabbits against dopamine or noradrenaline conjugated to thyroglobulin with glutaraldehyde. These antisera, tested in enzyme linked immunosorbent assay and immunohistochemistry specifically recognized their homologous antigens. With the aid of anti-tyrosine hydroxylase, anti-aromatic aminoacid decarboxylase, anti-dopamine-beta-hydroxylase, anti-dopamine, and anti noradrenaline antisera, immunohistochemical reactions were performed on glutaraldehyde fixed sections of sheep diencephalon in order to determine the presence of dopamine in the catecholaminergic group A15. Perikarya of this nucleus were stained with anti-tyrosine hydroxylase, anti-aromatic aminoacid decarboxylase and anti-dopamine, but not with anti-dopamine-beta-hydroxylase or anti-noradrenaline. Both of these latter antisera stained fibers within this area. So as recently found in the rat, we could conclude that dopamine is present in group A15 of the sheep. PMID- 2312362 TI - [Cytologic assessment of the nasal smear. A valuable diagnostic method in routine ENT practice]. AB - The cytological evaluation of a nasal smear is described as a helpful but almost forgotten method in daily rhinological practice, especially for the differentiation of rhinitis. With the help of pre-stained, ready-to-use slides it is a simple method available within minutes without any laboratory. The diagnostic significance of cells and crystals found in nasal smears is explained. PMID- 2312363 TI - [The value of radiotherapy in the treatment of esthesioneuroblastoma]. AB - Three cases of aesthesioneuroblastoma highlight the problems of treatment of these extremely rare tumours. These tumours of the olfactory epithelium arise in the nasal cavity and invade the paranasal sinuses, the orbit and the skull base. As symptoms occur late in the disease, most cases are advanced when diagnosed. Early cases can be treated by surgery, by irradiation or by a combination of, but the local control rate is about 60% regardless of the treatment. Chemotherapy should be used in addition to operation and irradiation, especially in advanced cases with nodal and distant metastases. An irradiation dose of 40-60 Gy is recommended. CT-aided treatment planning, sophisticated irradiation techniques, the use of high-energy photons and reliable immobilization measures are indispensable. A 5-year survival rate for all stages of 50% is reported. The recurrence rate in advanced stages is high, so that the benefits and risks of the different, combined treatment modalities must be evaluated carefully. PMID- 2312364 TI - [Essential blepharospasm and botulinum toxin. An electrophysiologic study]. AB - Thirty-five patients with essential blepharospasm were investigated electrophysiologically after local treatment with subcutaneous periocular injections of botulinum toxin. In all patients the blink reflex was measured on both sides. The results showed in some cases reproducible changes in the reflexes, indicating a central supranuclear origin for the spasm. Furthermore, an influence of afferent information on the "spasm threshold" via the trigeminal nerve is suggested. PMID- 2312365 TI - [Revision of the parotid--assessing the risk and indications status for re parotidectomy]. AB - Recurrences of benign and malignant tumors and inflammatory complications are the main indications for revision parotidectomy. Many of these operations could be avoided if the primary surgical procedure had been adequate. Revision parotidectomy is difficult to perform when the facial nerve is embedded in scar tissue. Indications for and risks of revision parotidectomy are demonstrated for typical situations such as recurrent pleomorphic adenomas and malignancies, postoperative fistulas, and recurrences of previously operated chronic parotitis. PMID- 2312367 TI - What will it take to reduce the incidence of breast cancer? PMID- 2312366 TI - AZT indication extended to use in children. PMID- 2312368 TI - Education--not legislation--resolves benzodiazepine abuse. PMID- 2312369 TI - Wound complications following modified radical mastectomy: an analysis of perioperative factors. AB - To assess the effect of perioperative factors on the incidence of postoperative wound complications, the authors retrospectively analyzed 101 patients who had undergone modified radical mastectomy. These factors included age, body weight, operative techniques, estimated blood loss, wound-catheter drainage, extent of axillary dissection, nodal involvement, and length of hospital stay. Complications included seroma (10.9%), wound infection (8.9%), wound necrosis (5%), hematoma (3%), lymphedema (2%), and pneumothorax (1%). The logistic regression method was used to analyze the data. When electrocautery was used to create the skin flaps, the probability of a wound complication was .462, a 44% increase over that calculated for the cold-knife technique (P = .05). A prolonged hospitalization accompanied the occurrence of a wound complication. No other factors reached statistical significance. PMID- 2312370 TI - Myocarditis: a clinical perspective. AB - Myocarditis can have many diverse presentations ranging from ventricular arrhythmias to congestive heart failure, secondary to dilated cardiomyopathy. The recent resurgence of endomyocardial biopsy has greatly enhanced our ability to diagnose this intriguing entity. The biopsy has shown that unexplained arrhythmias have a 15% to 29% incidence of myocarditis, while those with an idiopathic congestive cardiomyopathy have a biopsy-proved range of 9% to 63%. The cause of this process has, at times, been blamed on viruses, but definite cause and-effect relationships are mostly conjecture and anecdotal. The current role of immunosuppressive therapy in myocarditis is potentially promising, and may alter the subsequent course of the illness. PMID- 2312371 TI - Human immunodeficiency virus disease training: a 'how to' guide. AB - As the HIV epidemic spreads, throughout the United States, and as an increasing number of persons become infected with the virus and manifest its many complications, more and more physicians are being asked to give presentations on HIV disease to professional and community groups. This is especially true since AIDS education has become a primary prevention tool. The author provides guidelines for giving a talk on AIDS. The general principles are applicable to presentations both to other health professionals and to lay-community groups. The outline can be varied, and the lecture material can be expanded or summarized to meet the needs of the particular audience. Sources for further information are also provided. PMID- 2312372 TI - Chronic neutropenia following gold therapy. AB - We describe the first case of chronic neutropenia of 17 years' duration following gold therapy in a 53-year-old woman given a 1-g course of gold therapy in 1965 for treatment of seropositive rheumatoid arthritis. Although she had a good response to the gold therapy, her originally normal leukocyte count fell to 1.2 x 10(9)/L. Over the subsequent 17 years, she required multiple hospitalizations for recurrent skin, mouth, and respiratory tract infections. Serial leukocyte counts failed to show a cyclical nature to the chronic neutropenia. Normal results of a technetium Tc 99m spleen scan and lack of increased bone marrow leukocyte precursors rendered a diagnosis of Felty's syndrome unlikely. A bone marrow biopsy specimen revealed an isolated reduction in the number of myeloid precursors, which is consistent with gold-induced bone marrow toxicity. This patient's relative freedom from serious life-threatening infections remains enigmatic, but is undoubtedly related to her ability to augment another phagocytic cell line, and the remarkable phagocytic activity of her monocytes appears to have well compensated for her neutropenia. This activity was most likely responsible for her long-term survival. PMID- 2312373 TI - A call for common understanding of animal welfare, animal rights, and animal well being. PMID- 2312374 TI - Dooming animals to no life at all? PMID- 2312375 TI - Ultrasonic flea collars. PMID- 2312377 TI - FDA finds no residues in milk; Weiss doubtful. PMID- 2312376 TI - Interpretation of "ECG of the Month" defended. PMID- 2312378 TI - Weiss wants extra-label use policy eliminated. PMID- 2312379 TI - "How can I motivate my staff?". PMID- 2312381 TI - Pesticide monitoring results indicate food is safe. PMID- 2312380 TI - Environmental contaminants in food animal products low. PMID- 2312383 TI - Veterinary success--luck or skill? PMID- 2312382 TI - Sulfamethazine tolerance reduced. PMID- 2312384 TI - Agriculture policy analyst: a niche in public service. PMID- 2312385 TI - Food animal practitioners and food safety. PMID- 2312386 TI - Relationship of growth performance to pneumonia and atrophic rhinitis detected in pigs at slaughter. AB - Three commercial swine herds were selected for study, because pigs at slaughter consistently had lung lesions typical of bronchopneumonia and snout lesions consistent with atrophic rhinitis. Pigs were reared in the conventional system for each herd except that they were identified at birth and weighted at various intervals. At slaughter, individual pig lungs and snout were examined for lesions of pneumonia and atrophic rhinitis, respectively. Lesions were scored and correlated with growth indicators for each pig. Included in the growth indicators were: average daily gain (growing phase), average daily gain (finishing phase), average daily gain (total), and days to reach 104.5-kg body weight. Additionally, for each pig, scores for lung lesions were correlated to grades for snout lesions. Three correlation coefficients for measurements of pigs within herd B were significant and included days to 104.5-kg body weight and grades for snout lesions, -0.15 (P less than 0.02); average daily gain (finishing) and grades for snout lesions, 0.17 (P less than 0.01); and average daily gain (total) and grades for snout lesions, 0.16 (P less than 0.01). Contrary to findings in other investigations, pigs that attained market weight at the youngest age did not have the lowest score for lung lesions, the lowest grade for snout lesions, or the least extensive or severe lesions. Combining data from all 3 herds, the mean scores for lung lesions and mean grades for snout lesions decreased significantly (P less than 0.05) as the age of pigs at slaughter increased. All other statistical correlations were not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312387 TI - Induced Tritrichomonas foetus infection in beef heifers. AB - Four virgin beef heifers were inoculated intravaginally with 7 x 10(6) Tritrichomonas foetus organisms. Protozoal colonization of the vagina, cervix, and uterus developed within the first week after inoculation. Protozoa were no longer detected in secretions from these regions at approximately the same time in each heifer. Trichomonads were detected in reproductive tract secretions for 13 to 28 weeks. Eight weeks after clearance of trichomonads from the reproductive tract, a second infection was established in 2 of the 4 heifers by intravaginal inoculation of T foetus. The second infections were maintained for up to 4 weeks. The diagnostic sensitivity of wet-mount examination of the reproductive tract secretions was 30%, compared with 78% for culture of trichomonads in secretions. Collection and culturing of specimens of cervical and vaginal mucus provided the most reliable method for diagnosis of trichomoniasis during induced infection of heifers. PMID- 2312388 TI - Bradycardia in cattle deprived of food. AB - Bradycardia was documented in 12 cattle from which food has been withheld for 48 hours in preparation for general anesthesia and an elective surgical procedure. The heart rates decreased by a mean of 14 beats/min, and 4 cows had sinus arrhythmia. To evaluate this finding, the heart rates of 21 clinically normal cattle were evaluated before and after food was withheld for 48 hours. Bradycardia developed in all of the clinically normal cattle, with the mean decrease in heart rate being 23 beats/min. Five of the clinically normal cows developed sinus arrhythmia. It was concluded that bradycardia and sinus arrhythmia in cattle are associated with deprivation of food. PMID- 2312390 TI - Management of tracheal stenosis in a dog. AB - A 28-month-old Cocker Spaniel was treated for tracheal laceration after bite wound injury of the ventral area of the neck. Tracheal stenosis developed after surgical repair of the trachea. Bougienage failed to prevent recurrence of clinical signs of upper airway disease associated with tracheal stenosis. Resection of the stenotic lesion and tracheal anastomosis improved tracheal diameter and alleviated clinical signs of upper airway disease. A pulmonary function test (tidal breathing flow-volume loop) was used to assess upper airway function. PMID- 2312389 TI - Bone scintigraphy in the initial evaluation of dogs with primary bone tumors. AB - Bone scintigraphy was performed as part of an initial diagnostic evaluation of 70 dogs admitted with primary bone tumors during a 2-year period. Tumors involved major long bones of the appendicular skeleton and included 62 osteosarcomas, 6 fibrosarcomas, and 2 chondrosarcomas. All dogs were free of radiographically detectable pulmonary metastases. Bone scintigraphy was not of value in distinguishing among various types of primary tumors. One dog with an ulnar chondrosarcoma had a scintigraphically detectable occult osseous metastasis or synchronous primary tumor, and 1 dog with osteosarcoma had a scintigraphically detectable lymph node metastasis. Pulmonary metastases were not detected scintigraphically. Of the 70 dogs, 44.3% had areas of increased isotope uptake associated with nonneoplastic disease processes. PMID- 2312391 TI - Primary jejunal osteosarcoma associated with a surgical sponge in a dog. AB - Primary jejunal osteosarcoma was diagnosed in association with a surgical sponge in a dog. The tumor was biologically aggressive, resulting in widespread metastasis throughout the abdomen within 2 months of surgical resection. Microscopic examination of the resected osteosarcoma revealed strands of gauze material throughout the tumor mass. It was theorized that the presence of a sponge foreign body may have resulted in malignant transformation of adjacent tissues similar to what has been reported to occur after internal fixation of some long-bone fractures. PMID- 2312392 TI - Polyostotic hyperostosis associated with oviductal tumor in a cockatiel. AB - A 10-year-old female cockatiel in a thin and depressed condition and with a 1 X 2 cm soft abdominal swelling was hospitalized. Radiography revealed a well circumscribed mass containing punctate areas of mineralization, displacing the gizzard cranially in the caudodorsal portion of the abdomen. There was bilateral, symmetric, generalized, increased medullary opacity of the radius, ulna, carpometacarpus, femur, tibiotarsus, and tarsometatarsus. These findings were compatible with polyostotic hyperostosis secondary to an estrogen-secreting tumor. Euthanasia and necropsy were requested. A small area of neoplastic cells in the oviduct was identified histologically, but most of the tissue mass consisted of necrotic cellular debris. There was no metastasis. Sagittal secretions of decalcified radiopaque bones revealed up to 60% filling of medullary cavities with bone spicules. Although clinical and radiographic findings were compatible with an estrogen-secreting tumor, osteopetrosis, metastatic neoplasia, hypertrophic osteopathy, and metabolic bone disease were included in the initial differential diagnosis. The absence of metastasis and the confinement of the tumor within the oviduct would have made surgical removal a possible approach to treatment. PMID- 2312394 TI - Behavioral problems in old dogs: 26 cases (1984-1987). AB - Among 26 dogs greater than or equal to 10 years old, the most frequent owner complaints relating to behavioral problems were destructive behavior in the house (n = 10), inappropriate urination or defecation in the house (n = 10), and excessive vocalization (n = 7). The most frequent behavioral diagnoses were separation anxiety (n = 13) and breakdown of housetraining (n = 6). Most of the behavioral problems in the 26 dogs began after the dogs reached the age of 10 years, and most of the dogs had been owned for many years without having behavioral problems. Few behavioral problems in old dogs had a medical basis. Most cases of inappropriate urination or defecation in the house were not related to urinary or fecal incontinence, but were exacerbated by problems such as degenerative joint disease and renal disease. Behavioral therapy is appropriate for behavioral problems in old dogs, and, taking into account an old dog's health and physical limitations, techniques used are the same as for younger dogs. PMID- 2312393 TI - Anaerobic bacterial pneumonia with septicemia in two racehorses. AB - Anaerobic bacterial pneumonia with septicemia was diagnosed in 2 Thoroughbred racehorses referred with respiratory tract disease that had failed to respond to initial treatment with various antibiotics including penicillin and trimethoprim sulfamethoxazole. Multiple anaerobic organisms, including Bacteroides spp and Fusobacterium spp, were isolated from blood and transtracheal aspirates obtained from both horses and from aspirates of cutaneous nodules obtained from 1 horse. The latter horse responded to metronidazole treatment followed by procaine penicillin G administration and regained its health over the following 6 months. The other horse did not respond as favorably to a similar antibiotic regimen and died following an acute episode of pulmonary hemorrhage after remaining intermittently febrile for 7 weeks. Although in vitro antimicrobial susceptibility tests indicated that all anaerobic organisms isolated from both horses were susceptible to penicillin, the infection in these horses responded poorly to initial treatments with this drug. We speculated that adequate penicillin concentration was not attained in the deep foci of infection in the lungs. Animals with anaerobic bacterial infections that fail to respond to penicillin or from which penicillin-resistant anaerobes are isolated may benefit from treatment with metronidazole. PMID- 2312395 TI - Cat aggression redirected to people: 14 cases (1981-1987). AB - Among 27 cases of cat aggression manifested toward people, 14 cases were diagnosed as redirected or probable redirected aggression, because the cat was already highly aroused by other stimuli before attacking a person. A detailed behavioral history enabled identification of arousing stimuli. The most common arousing stimulus was the presence of another cat. Other arousing stimuli included high-pitched noises, visitors in the house, a dog, an unusual odor, and being outdoors unexpectedly. Medical problems or other behavioral abnormalities were not detected in any of the cats that could explain their aggressive behavior. Management consisted of avoidance or elimination of arousing stimuli wherever possible and extensive client education. On follow-up there was no recurrence of redirected attacks in 4 cats, variable decreases in the severity and frequency of attacks in 5 cats, and no change in 1 cat. Three cats were euthanatized, including one that had shown some improvement. Follow-up information was not available for the 2 remaining cases. Redirected aggression in cats is not well documented and may be misdiagnosed as idiopathic aggression or other behavioral abnormality. Although redirected attacks may be sudden, severe, and frightening, with careful management, a favorable outcome is possible. PMID- 2312397 TI - Longitudinal study of semen quality of unexposed workers: sperm head morphometry. AB - As part of a longitudinal study of human semen characteristics of unexposed workers, sperm head measurements were made using image analysis (Image Technologies Corp., Deer Park, NY). Morphometry was conducted on monthly samples from 45 men for 9 months. Measurements of area, perimeter, length, width, the width-length ratio, and the oval factor (4 [pi] area/perimeter) of 100 sperm heads per sample were obtained. The variability within a sample, between monthly samples from the same individual, and between individuals were calculated for each parameter. Tolerance intervals for each parameter were calculated, and are expected to contain 75% of all individual measurements. Similar intervals were calculated for the means and coefficients of variation of a semen sample. The largest source of variability was attributed to individual cell variation within a semen sample. PMID- 2312396 TI - Cyclosporine: its effects on testicular function and fertility in the prepubertal rat. AB - The authors examined the effects of the immunosuppressive drug cyclosporine (CsA) on the male reproductive system in prepubertal rats. Twenty-one-day-old rats were subcutaneously injected with either cremaphorsaline vehicle or CsA (1 and 2 mg/kg/d). The animals were treated until they were 66 days old. Cyclosporine did not affect the weights of the body or testis but decreased the weights of all sex accessory organs. Quantitative analysis of the tubules in stage VII of spermatogenesis revealed a decline in the cell counts of pachytene spermatocytes and step VII spermatids. Testicular and epididymal sperm counts and motility were decreased by 50% and fertility by 60%. Cyclosporine lowered serum testosterone despite an elevation of LH, indicating that the drug directly inhibited testosterone synthesis. Serum creatinine levels were normal in the treated animals, precluding renal failure as the cause for this impairment. Intratesticular concentrations of pregnenolone and 17-hydroxy progesterone were significantly elevated, while those of progesterone, androstenedione, and testosterone were markedly reduced. Determination of steroidogenic enzyme activities indicated that the administration of CsA inhibited the activity of delta 5-3B-hydroxy steroid dehydrogenase-delta 5-4 isomerase (3 beta-HSD). These results clearly indicate that CsA in the doses used is harmful to the male reproductive function in prepubertal rats. PMID- 2312398 TI - Sperm creatine kinase activity in fertile and infertile oligospermic men. AB - The authors examined the value of sperm creatine-kinase (CK) activity parameters to predict sperm fertilizing potential of oligospermic men. Two patient groups from our intrauterine insemination program were studied: fertile oligospermic (32 men/46 specimens) and infertile oligospermic (19 men/82 specimens). In the initial specimens, the CK activities were (mean + SEM IU CK/10(8) sperm): 0.53 +/ 0.09 and 1.17 +/- 0.19 (P less than 0.001). The corresponding values in the swim up fractions were 0.32 +/- 0.06 and 0.67 +/- 0.08 (P less than 0.001). In a subset of samples by fertile (N = 33) and infertile (N = 66) oligospermic men who had close to identical sperm concentrations (11.9 +/- 0.9 vs. 11.9 +/- 0.5 million sperm/ml) and motility values (23.7 +/- 1.7 vs. 23.0 +/- 1.3%), the CK activities were significantly lower in the fertile group in both the initial (P = 0.02) and in the swim-up (P = 0.002) samples. A logistic regression analysis of all 160 study samples (including 21 normal men/32 samples) further demonstrated that CK activities were predictive of fertilizing potential, whereas sperm concentrations of the samples provided no additional contribution. Sperm CK and similar biochemical markers will facilitate selection of men for various approaches in assisted reproduction. PMID- 2312399 TI - Evidence for a role of cysteinyl leukotrienes in mouse and human sperm function. AB - The in vitro fertilizing capacity of mouse spermatozoa was inhibited by FPL 55712, a receptor antagonist of the cysteinyl-containing leukotrienes LTC4, LTD4, and LTE4. Inhibition occurred whether the compound was present in the medium during the capacitation period or during the fertilization period. Additionally, FPL-55712 inhibited the penetration of human spermatozoa into zona-free hamster oocytes. Inhibition of fertilization did not appear to be caused by an effect on sperm motility or on the oocyte. These observations suggest that mouse and human spermatozoa require cysteinyl leukotriene activity for both fertilization and oocyte penetration. PMID- 2312400 TI - Human sperm motion analysis by automatic (Hamilton-Thorn Motility Analyzer) and manual (Image-80) digitization systems. AB - Two systems allowing quantitative, objective analysis of sperm movement were compared: 1) the Hamilton-Thorn Motility Analyzer (HTM), in which sperm images are digitized automatically, and 2) the Image-80, a modified image-analysis system in which sperm movement is digitized manually by hand tracing from videotape (Tessler and Olds-Clarke, 1985). Videotapes were made of human spermatozoa obtained by a swim-up procedure. The same videotape frames were analyzed by both systems. The mean percentage of motile spermatozoa was similar as judged by eye with either the HTM or Image-80 monitors and as reported by the HTM. For every motile spermatozoon, two motility parameters were calculated: linearity (a measure of track shape) and curvilinear velocity at 30 frames/second (a measure of track speed). When samples from five donors were averaged, there were no significant differences in mean linearity between automatic and manual systems. Also, linearity as reported by the HTM and Image-80 systems for the same track was significantly correlated (r = 0.72; N = 80). Whereas the absolute values for curvilinear velocity were slightly but significantly higher for the Image-80 system than for the HTM system, their correlation was also significant (r = 0.91). Since the two systems provide comparable data on percentage of motile sperm as well as speed and path shape parameters, this suggests that the HTM automatic digitization is accurate for images of human spermatozoa. PMID- 2312401 TI - Addition of hypotaurine can reactivate immotile golden hamster spermatozoa. AB - Hamster epididymal spermatozoa became virtually immotile following washing and dilution in chemically defined medium (TLP-PVA). The sperm motility factors (penicillamine, hypotaurine, and epinephrine: PHE) were examined for their ability to reactivate immotile sperm. Sperm could be reactivated by addition of PHE at 1 h of incubation. Hypotaurine alone was capable of reactivating sperm motility, but epinephrine and penicillamine together were not. However, overall sperm motility and percentage of motile sperm during incubation were higher when PHE components were used in combination than when hypotaurine was used alone. Addition of hypotaurine to immotile sperm suspensions could be postponed for up to 6 h with subsequent recovery of sperm motility, although the degree of recovery of motility declined progressively with each hour that addition of hypotaurine was delayed. The rescuing effect of hypotaurine was due to an increase both in the percentage of motile sperm and in the quality (grade) of sperm motility. The data show that hypotaurine is required for expression of sperm motility in the hamster, and support the concept that the loss of hypotaurine from sperm following washing and dilution is responsible for the sperm-immobilizing effect of these procedures. Additionally, the data demonstrate that hamster sperm can remain viable for several hours after becoming immotile, and that many of the immotile sperm are capable of being reactivated. PMID- 2312402 TI - Resorthiomycin, a novel antitumor antibiotic. II. Physico-chemical properties and structure elucidation. AB - Resorthiomycin was revealed to be a new antibiotic with a molecular weight of 284 and a chemical formula of C14H20O4S as determined by MS and elemental analysis. The structure of resorthiomycin was determined to be 6-acetyl-4-(3-hydroxybutyl) 2-methyl-5-methylthioresorcinol by IR spectrum and 1H and 13C NMR. PMID- 2312403 TI - Resorthiomycin, a novel antitumor antibiotic. III. Potentiation of antitumor drugs and its mechanism of action. AB - Resorthiomycin suppressed the clonogenic activity of a multidrug-resistant mutant cell line of Chinese hamster V79 cells more potently than its parental cells. Moreover, resorthiomycin at 40 micrograms/ml potentiated the cytotoxic activity of vincristine and actinomycin D on V79 cells over 3-fold. Uptake of [3H]actinomycin D into V79 cells was stimulated 2-fold by 40 micrograms/ml of resorthiomycin during 2 hours incubation. On the other hand, incorporation of [3H]thymidine and [3H]uridine into mouse leukemia L5178Y cells was inhibited in a dose-dependent manner at resorthiomycin concentrations ranging from 5 to 40 micrograms/ml. In ATP-depleted L5178Y cells, membrane transport of [3H]thymidine and 2-[3H]deoxyglucose was strongly suppressed by resorthiomycin. These results suggest that resorthiomycin acts on the plasma membrane and perturbes some membrane function. PMID- 2312404 TI - A new inhibitor of protein kinase C, RK-286C (4'-demethylamino-4' hydroxystaurosporine). I. Screening, taxonomy, fermentation and biological activity. AB - In the course of our screening program using a bleb-forming assay, a new inhibitor of protein kinase C (PKC) was found in the fermentation of a streptomycete. The inhibitor, RK-286C (4'-demethylamino-4'-hydroxystaurosporine), inhibited the morphological change of K562 cells, a human chronic erythroleukemia cell, induced by phorbol 12,13-dibutylate at the concentration of 3 microM. The same concentration of the compound inhibited the activity of PKC in vitro and the aggregation of rabbit platelets induced by collagen and arachidonic acid. PMID- 2312405 TI - A new inhibitor of protein kinase C, RK-286C (4'-demethylamino-4' hydroxystaurosporine). II. Isolation, physico-chemical properties and structure. AB - RK-286C, a new inhibitor of protein kinase C, has been found by the bleb-forming assay using K562 cells. It was produced by Streptomyces sp. RK-286 and purified by solvent extraction, silica gel chromatography and preparative HPLC. Spectrometric analysis revealed that the structure is 4'-demethylamino-4' hydroxystaurosporine. PMID- 2312406 TI - Antibiotics from basidiomycetes. XXXII. Strobilurin E: a new cytostatic and antifungal (E)-beta-methoxyacrylate antibiotic from Crepidotus fulvotomentosus Peck. AB - Strobilurin E is a novel antibiotic of the (E)-beta-methoxyacrylate (MOA) class produced by mycelial cultures of the agaric Crepidotus fulvotomentosus. In addition to an inhibition of fungal respiration, a feature of all MOA antibiotics, the compound exhibits very high cytostatic activities which are accompanied by reversible morphological alterations of the cells. PMID- 2312407 TI - Effect of anesthesia on acoustically evoked middle latency response in guinea pigs. AB - Increased recent interest in the middle latency response (MLR) has necessitated a clarification of the possible effects of anesthesia on the response. Our study was designed to examine the changes, in the guinea pig MLR, which occurred during anesthesia with ketamine, xylazine or both ketamine and xylazine. Under anesthesia the response remained present and the threshold remained stable. After anesthesia, significant changes in amplitude, latency, and general morphology of the waveform took place, however these were consistent and predictable. For studies requiring the MLR, it is best to avoid anesthetic agents. However, with care the MLR can be used as a reliable measure of auditory system sensitivity under anesthesia. PMID- 2312408 TI - Cholinergically-induced changes in outward currents in hair cells isolated from the semicircular canal of the frog. AB - Two cholinergically-induced modulations of membrane conductances have been identified in hair cells isolated from the crista ampullaris of the leopard frog (Rana pipiens), using the whole cell recording configuration of the patch clamp technique. Of 56 crista hair cells tested, 28 showed drug-induced changes in membrane current or membrane potential which were repeatable and could be reversed with washout of drug. The predominant effect (observed in 20 hair cells) of acetylcholine (Ach, 100 microM) to 1mM) or carbachol (1 microM to 50 microM) applied to these hair cells was the reduction of an outward current corresponding to a change in conductance of approximately -0.22 nS. This action by Ach on hair cells has been inferred from previous studies of afferent fiber discharge which reported an increase in firing rate with stimulation of efferent fibers or exogenous application of cholinomimetics (Bernard et al., 1985; Valli et al., 1986; Guth et al., 1986; Norris et al., 1988a). The Ach-induced reduction in outward current was associated with a depolarization of the zero-current membrane potential by approximately +2.5 mV. In a total of 8 hair cells, an Ach-induced reversible increase in outward current was recorded. Changes in conductance were approximately +0.13 nS and were associated with a hyperpolarization of the zero current membrane potential by approximately -2.2 mV. This current increase is likely to be responsible for the inhibitory post-synaptic potentials (IPSPs) which have previously been recorded intracellularly from acoustico-lateralis hair cells during stimulation of the efferent innervation (Flock and Russell, 1976; Ashmore and Russell, 1982; Art et al., 1984, 1985). Of the remaining 28 hair cells, six cells failed to exhibit any change in membrane conductance or membrane potential in the presence of cholinomimetics while an additional 15 cells exhibited decreases, and 7 cells exhibited increases in outward conductance, during application of Ach or carbachol, which were neither reversible with washout nor repeatable. The Ach-induced decrease in outward current could be reversible blocked by removal of Ca2+ from the external solution. The antagonism of the Ach-induced decrease in outward current by atropine (10(-5) M) suggests that this current may correspond to a facilitatory, 'atropine-preferring' Ach receptor mediated response previously identified in the isolated semicircular canal (Norris et al., 1988a).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2312409 TI - Two-tone interactions in inner hair cell receptor potentials: AC versus DC effects. AB - Two-tone suppression was studied in both ac and dc receptor potentials recorded from inner hair cells in the third turn of the guinea pig cochlea. Frequency response functions for the ac component obtained at moderate intensities indicate that frequency selectivity is enhanced when a high-side suppressor is added to the stimulus. This occurs because the largest reductions in magnitude take place well above and below the characteristic frequency (CF) of the cell. Changes near CF are relatively small. In contrast, frequency response functions for the dc receptor potential become broader in the presence of an excitatory suppressor. The significance of these findings for the processing of complex stimuli is considered. PMID- 2312410 TI - Postnatal development of 2f1-f2 otoacoustic emissions in pigmented rat. AB - Distortion-product emissions at 2f1-f2 were measured in developing, pigmented rats to determine the characteristics of the functional onset and maturation of these emitted responses. Distortion-product testing was conducted on postnatal days 12, 14, 18, 21, 24, 28, and 51. The geometric-mean frequencies of the primaries were tested at one-half octave intervals, between 4 and 11.3 kHz. No emissions were detected on postnatal day 12; however, by day 14, emissions were measured at geometric-mean frequencies between 5.7 and 11.3 kHz, but not at 4 kHz. By the 18th postnatal day, all animals had measurable emissions at 4, 5, 7, 8, and 11.3 kHz. Both the functional onset and maturation of high- to midfrequency emissions developed before those elicited by lower-frequency primaries. Response/growth or input/output functions for the higher frequencies exhibited 'adult-like' properties that included an increase in maximum amplitude and 'saturation' at high levels of stimulation by the third to fourth postnatal week. Maturation of the lower-frequency responses progressed at a slower rate. These results differ somewhat from those reported previously for the neonatal albino rat. However, the present findings were based upon a wider frequency range of primary tones, lower levels of acoustic stimulation, and a measuring system with a significantly lower noise floor. These results are consistent with documented periods of the anatomical maturation of the rat outer hair-cell system and establish a functional 'baseline' for future studies utilizing agents that damage the developing cochlea. PMID- 2312411 TI - Three-channel Lissajous' trajectories of auditory brainstem evoked potentials: contribution of fast and slow components to planar segment formation. AB - Three-Channel Lissajous' Trajectories (3CLT) of Auditory Brainstem Evoked Potentials (ABEP) to clicks were obtained after finite impulse response filtering in three frequency bands. These bands were chosen to replicate the widely used passband (100-3000 Hz) and to selectively enhance the definition of the 'pedestal' (10-240 Hz) or the first, third and fifth components (240-483 Hz). Quantitative measures of 3CLT were calculated to describe apex latencies, planar segment orientations, durations, trajectory amplitude peaks and their latencies. In addition, dipole moments at the latencies of apical points along 3-CLT were calculated. The planarity of ABEP 3-CLT segments persisted after selective enhancement of the 'pedestal' or the first, third and fifth components. These results rule out the suggestion that planarity of ABEP segments results from the interaction of the 'pedestal' with the superimposed faster components. These results demonstrate summation of 3-CLT planar segments ('a' 'c' and 'e' with the 'pedestal') to form new segments (wide-band 'a', 'c' and 'e'). With the exception of 'c', planar segments and the equivalent dipole moments associated with apexes did not change orientations across passbands. The effects of passband on the orientation of planar segment 'c' and the dipole moment of its apex are explained by its superimposition on the 'pedestal' in the wide-band records. A similar analysis of ABEP to clicks as compared to low-frequency stimuli (high-pass masked clicks) revealed no change in planarity nor in plane parameters. These results are compatible with the suggestion that the generators of the first, third and fifth ABEP components are curved fiber tracts. The planarity of the slow 'pedestal' may be due to the summation of slow synaptic potentials in auditory brainstem nuclei. These findings indicate that the generators of ABEP are composites that may be separated by selective lesion studies. PMID- 2312412 TI - Auditory brainstem responses to tonal stimuli in young and aging rats. AB - The auditory brain stem response (ABR) was studied in young adult and aged rats using 3,8 and 40 kHz tone pips. The expected inverse relationship between frequency and latency was observed in the younger group for waves I, II and III, while the response to the highest frequency stimulus had the longest latency at wave V. Absolute latencies for waves I through V each showed age-related increments with more pronounced changes occurring to 3 and 40 kHz stimuli than to the frequency of maximum sensitivity (8 kHz). Threshold increases with age for the highest frequency approximately doubled those for the lower frequencies. Examination of interpeak intervals (IPI) I-III, III-V and I-V revealed aging effects. The largest IPI I-V increment occurred to 3 kHz stimulation which reflects changes at both I-III and III-V sub-intervals. These results demonstrate electrophysiological correlates of aging due to transformations in the peripheral auditory system coupled with alterations in brainstem auditory pathways. PMID- 2312413 TI - Temporal modulation transfer functions for single neurons in the auditory midbrain of the leopard frog. Intensity and carrier-frequency dependence. AB - The sensitivity for amplitude modulation was investigated for 77 neurons from the auditory midbrain of the leopard frog. The results show that tuning to modulation frequencies occurs in about one-third of the units but is quite varied in its appearance. Two slightly differing characterizations for this tuning have been used; the overall response or rate-Modulation Transfer Function and the synchronized response or temporal-MTF (tMTF). The relation between the two characterizations is given by the vector-strength. Only one-third of the units showed a vector-strength that was significantly different from zero. Another synchronization measure, the synchronization factor which is based on the auto coincidence function, was significantly different from zero in about 3/4 of the units. The Best Modulation Frequency (BMF) and tuning band-width were found to be independent of both stimulus intensity and carrier frequency, although the average BMF for band-pass units was slightly higher for the amphibian papilla range of carrier frequencies than for the basilar papilla range (66 Hz vs. 49 Hz). The most frequent BMF for band-pass units was around 55 Hz, this does not correspond with the dominant modulation frequency of the mating call which is around 20 Hz. The synchronization measures were negatively correlated with intensity and independent of carrier frequency. The phase response of the tMTF was used to calculate the group delay. In contrast to the latency of the units the group delay was independent of stimulus intensity. PMID- 2312414 TI - Nonerythroid spectrin (fodrin) is a prominent component of the cochlear hair cells. AB - We studied the distribution of nonerythroid spectrin, fodrin, in surface preparations and cryosections of the cochlear hair cells as well as isolated hair cells of the guinea pig by using a monoclonal antibody (Mab) reacting with Mr 240 kD alpha-fodrin polypeptide. The Mab gave a strong reaction with the cuticular plate of both the inner and outer hair cells (IHCs and OHCs). Stereocilia were nonreactive and only a weak cell surface reaction was seen in the supporting cells. In the outer hair cells the upper turns of the cochlea, fodrin was observed in a cytoplasmic spiralling structure extending from the cuticular plate towards the cell nucleus. Some labelling was also seen along the cell surface membrane and in the synaptic region. The results suggest that fodrin may be an important constituent in the active processes of hair cells such as cell motility and/or signal transduction. PMID- 2312415 TI - Modelling the response of auditory midbrain neurons in the grassfrog to temporally structured monaural stimuli. AB - In a previous paper [Van Stokkum and Gielen, Hear. Res. 41, 71-86, 1989] a model was presented to describe the processing of monaural stimuli by the auditory periphery of the grassfrog. The main components of this model were: a middle ear filter, transduction and tuning of the haircell, short-term adaptation, action potential (event) generation with refractory properties, and spatiotemporal integration of converging inputs. The model is now extended to model auditory midbrain neurons as third order neurons. The mechanisms that generate selectivity for temporal characteristics of sound are adaptation, coincidence detection of second order neurons, temporal integration of third order neurons, and most important, event generation of the first, second and third order model neurons. Variation of the parameters of the model successfully reproduces the range of response patterns which have been obtained from eighth nerve fibres, dorsal medullary nucleus neurons, and torus semicircularis neurons without inhibition. With a single set of parameters the output of the model in response to a set of spectrally and temporally structured stimuli qualitatively resembles the responses of a single neuron to all these stimuli. In this way the responses to the different stimuli are synthesized into a framework, which functionally describes the neuron. PMID- 2312416 TI - Effect of contralateral auditory stimuli on active cochlear micro-mechanical properties in human subjects. AB - The present study investigates the possibility that contralateral auditory stimulation along medial efferent system pathways may alter active cochlear micromechanics and hence affect evoked oto-acoustic emissions in humans. A first experiment, involving 21 healthy subjects showed reduction of oto-acoustic emission amplitude under low intensity contralateral white noise (from 30 dB SPL, 10 dB SL, upwards). The effect is found for intensities below the acoustic reflex threshold (85.2 dB HL). A second experiment, involving 10 of the above 21 subjects, sought to rule out any technical artefact. Recording was again carried out, but after sealing of the contralateral ear with a silicon putty plug. No contralateral intensity effect on oto-acoustic emission amplitude was found for contralateral intensities below 65 dB SPL. In subjective perception terms (dB SL) an effect was found under sealing when the sound reached or passed above the 10 dB SL level. These two findings confirm the preceding experiment. The third experiment investigated the role of transcranial transmission of the contralateral auditory stimulus. 16 subjects having total unilateral deafness and one healthy ear were tested by the same procedure as above. No fall-off in oto acoustic emission amplitude was found for contralateral stimuli equal to or less than 80 dB SPL. There is thus a contralateral auditory stimulus effect on active cochlear micromechanics. The most appropriate explanation involves the medial cochlear efferent system, excited at brainstem level via the afferent auditory pathways. Alteration of active cochlear micromechanics seems promising at a basic level, pointing, as it does, to an interactive cochlear functioning which can be investigated by simple, non-intrusive, objective techniques which can be used with human subjects. We have here a model for functional exploration of the medial olivocochlear efferent system. PMID- 2312417 TI - The influence of the efferent system on acoustic overstimulation. AB - Since the first anatomical description by Rasmussen, the efferent innervation of the ear has been extensively investigated in order to establish its role in the hearing process. It is accepted that the olivocochlear bundle (OCB) influences the activity of the afferent fibers and through it, the peripheral ear is controlled by higher centers as well as connected to the other ear. Cody and Johnstone (1982) and Rajan and Johnstone (1983) concluded that the amount of ipsilateral temporary threshold shift (TTS) was reduced by simultaneous contralateral acoustic stimulation or by destroying the contralateral cochlea. They attributed the results to the efferent system. It was our aim to investigate whether, and under which conditions, the amount of TTS would be influenced by the efferent system. The efferent innervation was eliminated by cutting the superior vestibular nerve. Two factors influenced the magnitude of TTS; the integrity of the OCB and the functional condition of the contralateral ear. PMID- 2312418 TI - Haircell forward and reverse transduction: differential suppression and enhancement. AB - Cochlear outer haircells are believed to play a significant role in an amplification process which greatly enhances inner ear sensitivity. Haircell forward (mechanical-to-electrical) and reverse (electrical-to-mechanical) transduction may be involved. We have produced decreases in cochlear microphonic and increases in electrically-evoked cochlear emissions using the drug, furosemide. The data indicate forward and reverse transduction are not a simple bi-directional process and suggest that the outer haircells are part of a negative feedback system. PMID- 2312419 TI - Frequency selectivity of the middle latency response. AB - A forward masking paradigm was used to assess the frequency selectivity of the middle latency response (MLR). Tuning curves of the MLR were obtained in unanesthetized gerbils. Changes in the amplitudes of MLR waves A, B, and C with latency values of 10 to 13 ms, 14 to 17 ms, and 20 to 25 ms, respectively, were analyzed as a function of masker frequency and intensity. Tuning curves of the MLR were also compared to tuning curves of the auditory brainstem response (ABR), which was recorded simultaneously with the MLR. The MLR and ABR differed in their response to forward masking. The MLR was reduced in amplitude or eliminated by masker stimuli that had minimal or no effect on the ABR. Forward masking often caused variable and non-monotonic changes in the amplitude of the MLR. Tuning curves of the MLR indicate that the MLR is less frequency selective than the ABR. The MLR is an electrophysiological measure of auditory function central to the auditory brainstem. Therefore, it may provide information concerning central components of normal and pathological auditory function. However, because of the variability of MLR amplitudes with forward masking, tuning curves of the MLR are difficult to obtain and are not efficient for routine measurements of frequency selectivity. PMID- 2312420 TI - Digestibility of cotton plant by-product diets for sheep at two levels of intake. AB - Crossbred wethers (n = 48) were assigned randomly to 1 of 12 experimental diets, arranged in a 3 X 2 X 2 split plot to evaluate three levels of cotton plant by product (25, 50 and 75% CPB), two levels of NaOH treatment of CPB (0 and 4%) and two levels of monensin supplementation (0 and 30 ppm, DM basis) at two intake levels (70 and 90% of ad libitum). Intake was a within-lamb variable. Ad libitum intake was established over an initial 17-d adjustment period. Feed intake and fecal output were recorded during collection periods with aliquots retained for laboratory analysis. Intake was affected by a linear CPB X monensin interaction (P less than .06) with monensin depressing intake more at higher CPB levels. Neutral detergent fiber (NDF) digestibility decreased linearly (P less than .001) as the dietary level of CPB increased. NaOH treatment of CPB improved (P less than .001) the digestibility of organic matter (OM) and NDF. The supplementation of 30 ppm monensin resulted in greater (P less than .004) apparent digestibilities of NDF and hemicellulose (HC). Increasing daily feed intake from 70 to 90% of ad libitum decreased (P less than .004) digestibility of NDF, HC and ADF. PMID- 2312421 TI - Synchronization of estrus with melengestrol acetate and prostaglandin F2 alpha in beef and dairy heifers. AB - Beef (n = 783) and dairy (n = 209) heifers at 14 locations were used to evaluate the efficacy of feeding melengestrol acetate (MGA; .5 mg/d) for 7 d followed by an i.m. injection of 25 mg prostaglandin F2 alpha (PGF) on the last day of MGA feeding (MGA + PGF) to synchronize estrus. Untreated heifers (C) and heifers injected once i.m. with PGF served as contemporary controls. Heifers were observed for estrual behavior for a minimum of 38 d starting on the 2nd d of MGA feeding. Heifers in estrus from d 1 through d 60 after PGF injection were artificially inseminated (AI) or bred to bulls (d 30 to 60 post PGF only). During the 7-d MGA feeding period fewer (P less than .01) MGA + PGF (1.5%) than C (20.6%) or PGF (18.1%) heifers were observed in estrus. Percent of heifers in estrus d 1 to 6 post PGF was different among groups (P less than .05; 30.5, 52.8, 72.3 for C, PGF and MGA + PGF, respectively). More (P less than .01) MGA-fed (92%) than non-MGA-fed (C and PGF combined) heifers (85.4%) were observed in estrus during d 1 to 24. Conception rate (CR) during d 1 to d 6 was not different (P = .19) between C (58.9%) and MGA + PGF (51.2%) heifers; CR was lower (P = .01) for MGA + PGF than for PGF (68.3%) heifers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312422 TI - Effects of breed and wintering diet on heifer postweaning growth and development. AB - Fifteen spring-born Angus (AN) and 25 Brangus (BN) weanling heifers were used in a 2x5 factorial arrangement of treatments to evaluate the effects of breed and postweaning winter diet on heifer growth and development. Dietary treatments were warm-season perennial grass hay (H), ammoniated H (AH), H plus .68 kg/d cottonseed meal (HP), H plus .45 kg/d cottonseed meal plus 1.37 kg/d ground corn (HPE) and HPE plus 200 mg/d monensin (HPEM). Mean initial weight and age for the 107-d feed trial were 207 kg and 270 d. Brangus had .06 kg greater (P less than .05) ADG than AN during the trial. Although digestible DM intake (DDMI) relative to body weight was greater (P less than .10) for AN than for BN, ADG:DDMI was greater (P less than .05) for BN than for AN. Heifers fed H and AH lost weight, but heifers fed AH had 50% (P less than .05) less daily weight loss than those fed H. Daily gain increased (P less than .05) incrementally in response to sequential supplement additions of cottonseed meal (AH vs HP; -.10 vs .17 kg), ground corn (HP vs HPE; .17 vs .29 kg) and monensin (HPE vs HPEM; .29 vs .39 kg). Hay DM intake relative to body weight and DDMI were increased (P less than .01) by ammoniation. Intake did not differ between HPE and HPEM. Diet affected age at puberty (P less than .05), which decreased with increased dietary components. Weight differences among diet groups following the winter feed trial were largely eliminated prior to breeding. Nevertheless, H- and AH-fed heifers collectively weighed less (P less than .01) prior to breeding than did heifers of supplemented diet groups. Reproductive development tended to be adversely affected by weight loss during the postweaning period. PMID- 2312423 TI - Direct and maternal genetic effects due to the introduction of Bos taurus alleles into Brahman cattle in Florida: I. Reproduction and calf survival. AB - Pregnancy rate, calf survival rate to weaning and calf age at weaning of several types of crossbred cows (2/3 or more Brahman) were compared to those of straightbred Brahman and Angus cows over a 12-yr period at Subtropical Agricultural Research Station near Brooksville, FL. The purpose of this study was to determine the relative importance of additive vs nonadditive genetic effects on reproductive and calf survival traits in a population of cattle whose foundation was selected on the basis of superior reproductive performance under harsh environmental conditions. Best linear unbiased estimates (BLUE) of direct additive effect (measured as the deviation of Brahman additive breed effect from Angus) for pregnancy rate and calf age, measured as traits of the dam, were 6 +/- 3% and -7.2 +/- 2.1 d, respectively. Thus, Bos taurus germ plasm did not increase pregnancy rate but resulted in an earlier calving date. The BLUE of nonadditive (intralocus) direct genetic effects measured as deviations from intralocus group genetic effects in the parental breeds on pregnancy rate and calf age at weaning were 25 +/- 4% and -6.4 +/- 2.5 d. Nonadditive effects on pregnancy rate were the primary cause of the superior reproductive rates observed in Brahman crossbred cows. Calf survival was considered to be a trait of the calf, and BLUE of direct additive, direct nonadditive, maternal additive and maternal nonadditive genetic effects was obtained. Only maternal nonadditive genetic effects were found to have a significant effect on survival rate (9 +/- 4%). PMID- 2312424 TI - Direct and maternal genetic effects due to the introduction of Bos taurus alleles into Brahman cattle in Florida: II. Preweaning growth traits. AB - Records of birth weight (BW), weaning weight (WW) and condition score (CS) from 1,467 Brahman and Brahman X Angus crossbred calves from Brahman and crossbred Brahman sires and Brahman, crossbred Brahman and Angus dams were collected at the Subtropical Agricultural Research Station, Brooksville, Florida, from 1971 to 1982. Best linear unbiased estimates (BLUE) of Brahman sire and dam group additive genetic effects (as deviations from Angus) and Brahman X Angus dam and calf group nonadditive (intralocus) genetic effects (as deviations from intralocus group genetic effects in the parental breeds) were obtained. Linear combinations of these were used to compute direct and maternal Brahman additive and Brahman X Angus nonadditive (intralocus) group genetic effects. The respective BLUE of these four effects were 5.99 +/- 2.08, -5.70 +/- 1.91, .52 +/- 1.81 and 2.85 +/- .72 kg for BW; 9.60 +/- 10.29, 8.76 +/- 9.47, 9.47 +/- 8.96 and 20.95 +/- 3.56 kg for WW; and -1.10 +/- .55, 1.64 +/- .50, 1.47 +/- .47 and .05 +/- .19 units for CS. Linear combinations of the BLUE of sire, dam and calf group genetic effects can be used to predict the genetic worth of crossbred groups composed of any combination of Brahman and Angus breeding. Nonadditive maternal group genetic effects were the most important factor for BW and WW, whereas nonadditive direct group genetic effects were the most important for CS. PMID- 2312425 TI - Genetic analysis of absolute growth measurements, relative growth rate and restricted selection indices in red Angus cattle. AB - Performance records on 41,184 Red Angus cattle were analyzed and estimates of parameters calculated for absolute growth rate, relative growth rate and restricted selection indices. Heritability estimates for birth weight, 205-d weight, 365-d weight and postweaning gain were .46 +/- .02, .39 +/- .02, .40 +/- .02 and .36 +/- .02, respectively. Heritability estimates for preweaning, postweaning and postnatal relative growth rates were identical (.33 +/- .02). Heritability estimates for restricted selection indices were .31 +/- .02, .33 +/- .02 and .31 +/- .02 for weaning index, yearling index and postweaning index, respectively. The genetic correlation between preweaning and postweaning absolute growth rate was .15. The genetic correlation between consecutive measurements of relative growth rate (RGR) was -.33. Genetic correlations of birth weight with preweaning RGR and postnatal RGR were -.68 and -.71, respectively. Correlations among measures of relative growth rate using simulated data were similar to correlations of actual data, indicating that these relationships are the result of numerator/denominator relationships and not biological causes. The genetic correlation between weaning and postweaning indices was near zero. Small genetic coefficients of variation for preweaning and postnatal relative growth rates indicate further problems with the expression of growth in this manner. Restricted selection indices exhibited much larger genetic coefficients of variation than measurements of RGR. Genetic standard deviations were 7.8%, 7.2% and 13.7% of the means for weaning, yearling and postweaning indices, respectively. PMID- 2312427 TI - Effects of transportation on early embryonic death in mares. AB - Incidence of early embryonic death (EED) and associated changes in serum cortisol, progesterone and plasma ascorbic acid (AA) in transported mares were investigated. Mares were transported for 472 km (9 h) during either d 16 to 22 (T 3 wk, n = 15) or d 32 to 38 (T-5 wk, n = 15) of gestation. Blood samples were drawn from control, nontransported mares (NT-3 wk, NT-5 wk, n = 24) and transported mares pre-trip, midtrip, and at 0, 12, 24, 48 and 72 h post-transport and daily for the next 2 wk. Incidence of EED between transported and nontransported mares was not different (P greater than .05). Serum cortisol in all transported mares increased (P less than .05) relative to pre-trip values at midtrip and 0 h post-transport. Relative to NT mares, serum cortisol was higher (P less than .05) at midtrip in T-3 wk mares and 0 h post-transport in T-5 wk mares. Serum progesterone in all T mares increased (P less than .05) at midtrip relative to pre-trip values and was higher (P less than .05) in T-3 wk mares than in NT-3 wk mares at midtrip and 0 h post-transport. Post-transport decreases (P less than .05) in concentrations of progesterone were observed in mares that aborted. Plasma AA in transported mares increased (P less than .05) at midtrip in T-5 wk mares and decreased (P less than .05) relative to pre-trip values at 24 and 48 h post-transport (T-3 wk and T-5 wk mares, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312426 TI - Associations between genetic markers and growth and carcass traits in a paternal half-sib family of Angus cattle. AB - Segregation of polymorphic marker genes in a paternal half-sib family of Angus cattle was used to detect associations between genetic markers and quantitative traits. The half-sib family selected (n = 146) had a sire that was heterozygous at six polymorphic marker loci; BoLA-A (class I major histocompatibility complex), B, C and F blood group systems, serum transferrin and vitamin D binding protein. Segregation of alleles fit the expected ratios for all marker loci. Performance data analyzed for all half-sibs included birth, 205-d and 365-d adjusted weights and pre- and post-weaning average daily gains. Carcass data for steers (n = 61) included carcass weight, rib-eye area, 12th rib fat thickness, percent kidney, heart and pelvic fat and yield grade. Least squares means were compared for differences in performance and carcass traits between groups of half sibs that inherited alternative paternal alleles. Significant effects were found for two of the six marker systems. Half-sibs that inherited the chromosomal segment (CS) marked by the RBC-B system BGKOxY2A'O' phenogroup had heavier 205-d (9.1 kg) and 365-d (17.3 kg) adjusted weights, faster preweaning average daily gains (.04 kg) and less fat thickness (-2.6 mm) than sibs that inherited the CS marked by I2Y2E'1Y'. Also, sibs that inherited the CS marked by the BoLA-w2 allele had larger rib-eye areas (4.1 cm2) than sibs that inherited BoLA-w28. These data indicate the probable presence of genes linked to the RBC-B and BoLA systems that affect preweaning growth and lean muscle content. PMID- 2312428 TI - Differential compensatory growth in swine following control of feed intake by a high-alfalfa diet fed ad libitum or by limited feed. AB - Seventy-two castrated male four-way composite (Chester White x Landrace x Large White x Yorkshire) weanling pigs (17 kg initial BW) were used to determine the compensatory response of specific organs and whole body following a 3-wk period of restricted energy intake imposed by ad libitum-feeding an 80% alfalfa meal diet or pair-feeding an adequate corn-soybean meal diet to attain equal weight loss. Six pigs were killed at d 0 to provide baseline data. Six pigs from each diet group (control, C; alfalfa, A, restricted, R) were killed at d 21, after which all remaining pigs were fed C ad libitum to 35 d, 105 d or 126 d. Six pigs per group were killed at 35 and 105 d and four per group were killed at 126 d. Organ weight and carcass data were recorded for all pigs at all time intervals. Regression of organ and trimmed lean tissue weights on time was tested for linearity (d 1 to 126 for C and d 21 to 126 for A and R except d 35 to 126 for gastrointestinal tract traits for A and R); differences in organ weights between C, A and R at d 21 and d 35 were tested by a two-way analysis of variance. There was no evidence of a compensatory growth response to dietary energy restriction for 21 d except for rate of change in weights of liver and kidneys and backfat depth from 21 to 126 d and of gastrointestinal tract components from 21 to 35 d. Specific organs may exhibit compensatory growth over different time spans in young pigs in the absence of observable weight compensation at the whole-animal level. PMID- 2312429 TI - Effect of weaning, week postweaning and diet composition on pancreatic and small intestinal luminal lipase response in young swine. AB - The effects of weaning, week postweaning and diet composition on concentration of lipase in the pancreas and small intestinal lumen were investigated in weanling swine. In Exp. 1, lipase levels were evaluated in suckling pigs from 2 to 35 d of age and in pigs weaned at 21 or 35 d of age. Pigs weaned at 21 d of age were fed a corn-soybean meal diet with lipase levels measured from 3 to 28 d postweaning. Pancreas weights increased during the suckling period; they were lowered at 3 d postweaning and were lower at 7 d postweaning than in suckling pigs but increased linearly from 3 to 28 d postweaning. Lipase level per unit wet tissue and total pancreatic levels increased from 2 to 35 d of age in suckling pigs (P less than .01). Weaning at 21 d of age resulted in a decline (P less than .05) in lipase levels in the pancreas at 3 and 7 d postweaning, but the levels subsequently tended to increase between 7 and 28 d postweaning. Whereas relative lipase levels in the intestinal lumen increased from 2 to 35 d of age in suckling pigs, total luminal enzyme did not decline upon weaning when pigs were weaned at either 21 or 35 d of age. Total luminal lipase per unit empty body increased linearly (P less than .01) each week postweaning. In Exp. 2, a 2 X 2 factorial arrangement of corn oil (0 or 6%) and dried whey (0 or 25%) was used to evaluate digestive lipase levels in pigs weaned at 21 d of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312430 TI - Nutritive value of rubber seed (Hevea brasiliensis) meal: utilization by growing pigs of semipurified diets in which rubber seed meal partially replaced soybean meal. AB - Thirty-six four-way cross (Chester White X Landrace X Large White X Yorkshire) growing barrows and gilts were used to investigate the effects of replacing graded levels of protein from soybean meal with equivalent levels of protein from rubber seed meal in 16% CP semipurified diets on the performance characteristics, hematocrit, plasma metabolites and N utilization of pigs. The first diet (control) was largely cornstarch-soybean meal in which the soybean meal supplied all of the CP. In other diets, rubber seed meal replaced 10%, 20% and 30%, respectively, of the protein of soybean meal in the control diet. Twenty gilts were used in a 28-d growth trial and 16 barrows were used in an 8-d digestion trial (4-d collection). There were no differences (P greater than .05) in ADG, ADF intake and in the feed:gain ratios, even though there was a trend for lower ADG and gain:feed ratio as the level of rubber seed meal increased in the diet. There were no differences in hematocrit, but plasma protein and albumin tended to be depressed when rubber seed meal provided more than 10% of the dietary protein. Apparent digestibilities of GE, DM and N were lower with rubber seed meal at 20% of the protein than with any other diet, but apparent N retained and the percent of digested N retained were not depressed significantly (P greater than .05). Although rubber seed meal protein is of poorer quality than soybean meal protein for growing pigs, at least 10% of dietary protein can be provided by rubber seed meal without adversely affecting growth and N utilization. PMID- 2312432 TI - Incorporation and expression of a neo gene after transfer to caprine hematopoietic cells using a modified retrovirus. AB - The ability of the N2 retrovirus to introduce the selectable neo gene into (transform) caprine hematopoietic cells (CHC) was evaluated. Helper-free amphotropic retrovirus producing cells (RPC) were plated at approximately 1.0 x 10(5) cells per 25 cm2 tissue culture flask, cultured to 80% confluence and irradiated (1,500 rads) prior to CHC incubation. The CHC collected from three donor goats were washed and cultured for 24 h in either the RPC or control flasks. Cells were cultured in Dulbecco's Modified Eagles Medium containing 10% fetal calf serum (FCS) (DMEM) and 4 micrograms polybrene/ml. After 48 h of culture in fresh DMEM, cells were recovered and suspended in Iscove's DMEM supplemented with .3% gar, 12% FCS and 400 micrograms geneticin/ml (G418; neomycin) and transferred to 35-mm petri dishes (7.5 x 10(5) cells) for selection of G418 resistant cells. After 17 d of culture, plates were evaluated for total number of colony forming units (CFU, greater than 10 cells). Total number of CFU was greater (P less than .01) in treatment samples (means = 175, SEM = 70) than in control cultures (mean = 0, SEM = 0). The N2 retrovirus appears to be an effective vector for the transformation of CHC and may provide a means to introduce gene(s) into cells of domestic animals. PMID- 2312431 TI - Effect of transportation on the estrous cycle and concentrations of hormones in mares. AB - Effect of transportation on estrous behavior, duration of the estrous cycle, ovulation, pregnancy rates and concentrations of serum cortisol, plasma ascorbic acid (AA), LH, estradiol and progesterone in mares was investigated. Fifteen mares were transported for 792 km (12 h) during the preovulatory stage of estrus. Transported mares were bled immediately before transport (baseline), at midtrip and 0, 12, 24, 48 and 72 h post-transport and twice daily from d 1 before transport to d 1 (estrogen) or 3 (LH) post-ovulation. Blood samples also were taken for progesterone on d 0, 2, 6, 10, 15, 16, 17, 18, 19 and 20 post ovulation. Nontransported control mares (n = 15) were bled on the same schedule as transported mares. There was no difference (P greater than .05) in number of mares ovulating, estrous behavior, duration of the estrous cycle or pregnancy rate between groups. Cortisol in transported mares increased to concentrations greater (P less than .05) than those in control mares at midtrip and 0 h post transport. Concentrations of AA in transported mares also increased (P less than .05) at midtrip, then decreased (P less than .05) below baseline at 24 h post transport. Concentrations of LH and estradiol increased (P less than .05) above baseline throughout the blood-sampling period. Increases apparently were due to preovulatory surges of these hormones. Increase in LH concentrations in transported mares, however, was greater (P less than .05) than that in control mares at 0 h post-transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312433 TI - Vitamin A deficiency: serum cortisol and humoral immunity in lambs. AB - Serum cortisol and antigen-specific and polyclonal immunoglobulin G (IgG) concentrations were measured to investigate the relationship between vitamin A status and immune function in lambs. Twenty-four 3-mo-old crossbred ewe lambs weighing approximately 10 kg were each fed 900 g/d of a carotene-deficient diet. The 12 control lambs also received a 100,000 IU oral dose of vitamin A palmitate every 2 wk. All lambs were given primary and secondary antigenic challenges. Lambs were slaughtered at the end of the secondary challenge period. Liver vitamin A concentrations were greater (P less than .001) in the control animals (69.5 vs 1.3 micrograms/g wet tissue). Both groups of lambs exhibited a similar growth response until d 105, after which daily gain of the control lambs exceeded (P less than .03) that of the A-deficient lambs. Polyclonal serum IgG concentrations were greater (P less than .05) in the A-deficient lambs on d 49 to 124 and on d 151 (P less than .10). Ovalbumin-specific serum IgG concentrations tended to be greater in the control lambs throughout the primary and secondary challenge periods. Control lambs had greater titers on d 164 (P less than .07) and d 190 (P less than .03). Vitamin A status appeared to have no consistent effects on serum cortisol concentrations. Spleen weights were greater (P less than .002) in the A-deficient lambs. Lungs from 11 of 12 A-deficient lambs contained abscesses, as opposed to 1 of 12 for the control lambs. Both polyclonal and antigen-specific IgG concentrations were affected by vitamin A status. Serum cortisol concentrations did not appear to mediate this effect. PMID- 2312434 TI - Effects of lecithin and corn oil on site of digestion, ruminal fermentation and microbial protein synthesis in sheep. AB - Six Hampshire wethers with ruminal and duodenal cannulas were fed three diets in a replicated 3 X 3 latin square to compare phospholipids with triglycerides for their effects on ruminal digestion. The diets (56% concentrate, 44% bermuda-grass hay, air-dried basis) contained either no added fat (control), 5.2% soybean lecithin or 2.4% corn oil on a DM basis. All diets were isonitrogenous and both fat-supplemented diets had similar fatty acid and energy contents. Fat added to the diet, regardless of source, reduced digestibilities of DM, energy, ADF and fatty acids in the rumen but had no effect on total tract digestibility coefficients. Lecithin slightly increased (P = .06) fatty acid digestion in the hindgut compared to corn oil (91.0 and 87.0%, respectively). Both fat sources decreased (P less than .01) ruminal ammonia concentration and increased (P less than .10) N flow to the duodenum. Added fat also reduced ruminal (P less than .01) and total tract (P less than .05) N digestibilities. Microbial N flow to the hindgut was not affected by diet, but adding fat increased (P less than .06) true efficiency of microbial protein synthesis. Overall, phospholipids from soybean lecithin inhibited ruminal fermentation similarly to triglycerides from corn oil. Despite ruminal degradation of lecithin by microbial phospholipases as shown in other studies, feeding lecithin tended to increase fatty acid digestion in the hindgut. PMID- 2312435 TI - Intestinal supply of amino acids in sheep fed alkaline hydrogen peroxide-treated wheat straw-based diets supplemented with soybean meal or combinations of corn gluten meal and blood meal. AB - The intestinal supply of amino acids (AA) in sheep fed alkaline hydrogen peroxide treated wheat straw (AHPWS)-based diets supplemented with soybean meal (SBM) or corn grain plus combinations of corn gluten meal (CGM) and blood meal (BM) was measured in a 5 X 5 latin square. Sheep (avg wt 45 kg) with ruminal, duodenal and ileal cannulas were fed diets containing 65% AHPWS supplemented with the following protein sources: soybean meal (SBM), corn gluten meal (CGM), blood meal (BM), 2/3 CGM:1/3 BM and 1/3 CGM:2/3 BM. Total nitrogen (N) flow at the duodenum was not affected (P greater than .05) by protein source. Flows of bacterial N and AA increased (P less than .05) and flows of nonbacterial N and AA decreased (P less than .05) when wethers were fed SBM vs corn plus other protein sources. When diets contained SBM, quantities of total AA at the duodenum were lower (P less than .05) and the profile of AA supplied to the intestine was altered substantially. Total flows of AA at the duodenum and total quantities of AA disappearing from the small intestine were similar (P greater than .05) for all diets containing BM and CGM, but flows and disappearance of valine, histidine, lysine and arginine increased linearly (P less than .05), whereas flows and disappearance of leucine, isoleucine and methionine decreased linearly (P less than .05) as BM replaced CGM in the diets. Results suggest that quantities of individual AA flowing to the duodenum and disappearing from the intestine of wethers fed AHPWS-based diets can be altered by source of dietary protein. Furthermore, feeding protein sources resistant to ruminal degradation in combination may improve the profile of AA supplied to the intestine. PMID- 2312436 TI - Feeding value of coconut alcohol bottoms-bottoms for feedlot cattle. AB - Six crossbred steers (274 kg) with "T" cannulas in the rumen, proximal duodenum (6 cm from the pyloric sphincter) and distal ileum (20 cm from the ileal-cecal valve) were used in a crossover experiment to evaluate the feeding value of coconut alcohol bottoms-bottoms (CABB) in a finishing diet for feedlot steers. Dietary treatments consisted of a steam-rolled barley-based finishing diet supplemented with or without 6% CABB. The CABB was blended first with the steam rolled barley portion of the diet prior to adding the other dietary ingredients. Ruminal digestion of ADF and N was not affected (P greater than .10) by CABB supplementation. Added CABB decreased total tract digestibility of OM, ADF, lipid and DE by 5.65 (P less than .01), 29.4 (P less than .05), 57.4 (P less than .01) and 5.65%, respectively. Adjusting for constituent passage of the basal diet, estimated total tract digestibility of OM, DE and lipid of the supplemental CABB was 1.1, -.23 and 16.4%, respectively. CABB essentially has no feeding value in finishing diets for cattle. PMID- 2312437 TI - The effects of lysocellin and varying calcium levels on performance and ruminal and plasma characteristics of growing beef steers fed corn silage. AB - Twenty-four steers initially averaging 221 kg BW were used to evaluate the effects of lysocellin and calcium (Ca) level on performance and ruminal and plasma characteristics. Lysocellin at 0 or 22 mg/kg of diet and Ca at .3 or .6% were fed in a 2 X 2 factorial arrangement of treatments. Steers in individual pens had ad libitum access to a diet consisting of 80% corn silage and 20% (DM basis) of a protein, mineral and vitamin supplement. Ruminal fluid and blood samples were collected on d 42 and 85 of the 113-d trial. Steers fed the .6% Ca diet gained faster and required less feed/unit of gain than those fed the .3% Ca diet (P less than .05). There was a tendency for a lysocellin X Ca interaction for gain and feed efficiency (P less than .10). Lysocellin tended to depress performance when fed with .3% Ca, but it tended to improve gain and feed efficiency when fed with .6% Ca. Molar proportions of propionate were higher and those of acetate were lower (P less than .01) for steers fed lysocellin. Ruminal soluble Zn, Fe and Cu levels were higher (P less than .01) in steers fed lysocellin. Ruminal-soluble Ca (P less than .01) was higher and ruminal-soluble P and Na were lower (P less than .01) in steers fed .6% Ca. Plasma K was higher (P less than .05) in steers fed .6% Ca but it was lower (P less than .05) in steers fed lysocellin. Results of this study indicate that dietary Ca affects certain metabolic responses to lysocellin in growing cattle. PMID- 2312438 TI - Effects of treating corn silage with alpha-amylase and(or) sorbic acid on beef cattle growth and carcass characteristics. AB - The effects on beef cattle growth performance and carcass characteristics of feeding silages produced by altered fermentations were determined. Alpha-amylase was added at 0 or .05% (wet basis) and sorbic acid was added at 0 or .10% (wet basis) to chopped whole corn plants before ensiling in a 2 x 2 factorial arrangement of treatments. For three successive years, 40 beef heifers (224 kg) were fed these silages for 80 d, finished on corn-and-cob meal (107 d) and slaughtered when backfat thickness over the 13th rib reached 12 mm. Silages treated with alpha-amylase had a slightly higher percentage of N-free extract (P less than .10). Silages treated with sorbic acid had lower percentages of ADFN (P less than .10). During the silage-feeding phase, heifers fed silages treated with alpha-amylase gained more (P less than .01) daily than heifers fed the other two silages (.84 vs .78 kg) and they were more efficient (P less than .01) in weight gain per unit of dry feed consumed (.149 vs .139 kg). During the finishing phase, heifers that previously had been fed the alpha-amylase-treated silage continued to have higher (P less than .05) ADG (.93 vs .87 kg), although all were fed the same diet during this period. Added sorbic acid had no effect on ADG in either period. The percentage of kidney fat in heifers on the alpha-amylase treatments was increased (P less than .02, 2.2 vs 2.0). The biological mechanisms associated with the beneficial results of alpha-amylase addition are not understood yet. PMID- 2312439 TI - Supplementation of dormant tallgrass-prairie forage: I. Influence of varying supplemental protein and(or) energy levels on forage utilization characteristics of beef steers in confinement. AB - Three experiments were conducted to evaluate effects of supplemental protein vs energy level on dormant forage intake and utilization. In Exp. 1, 16 ruminally cannulated steers were blocked by weight (avg wt = 242 kg) and assigned randomly to a negative control or to one of three isocaloric supplement treatments fed at .4% BW: 1) control, no supplement (NS); 2) 12% CP, low protein (LP); 3) 28% CP, moderate protein (MP); 4) 41% CP, high protein (HP). In Exp. 2 and 3, 16 ruminally cannulated steers were blocked by weight (avg wt = 332 kg, Exp. 2; 401 kg, Exp. 3) and assigned randomly to a 2 x 2 factorial arrangement of treatments. The treatments contrasted low (LP) and high (HP) levels of supplemental protein (.66 g CP/kg BW vs 1.32 g CP/kg BW) with low (LE) and high (HE) levels of supplemental ME (9.2 kcal/kg BW vs 18.4 kcal/kg BW). In Exp. 1, forage DMI as well as ruminal DM and indigestible ADF fill at 4 h postfeeding were greater (P less than .10) with the MP and HP steers than with control and LP steers. Total DM digestibility increased (P less than .10) for supplemented steers (35.5% for control vs 47.3 for supplemented steers); however, LP depressed (P less than .10) NDF digestibility. In Exp. 2, forage DMI, indigestible ADF flow and liquid flow were depressed (P less than .10) in LP-HE supplemented steers. In Exp. 3, HP steers had greater (P less than .10) forage DMI, indigestible ADF fill values (4 h postfeeding), liquid volume and tended (P = .11) to have greater ruminal DM fill (4 h postfeeding). In summary, increased levels of supplemental protein increased intake and utilization of dormant tallgrass-prairie forage (less than 3% CP). Increasing supplemental energy without adequate protein availability was associated with depressed intake and digestibility. PMID- 2312440 TI - Supplementation of dormant tallgrass-prairie forage: II. Performance and forage utilization characteristics in grazing beef cattle receiving supplements of different protein concentrations. AB - Two experiments were conducted to evaluate the influence of supplemental protein concentration on the intake and utilization of dormant range forage by beef cattle. In Exp. 1,97 pregnant Hereford x Angus cows (avg wt = 454 kg) were assigned randomly to three isocaloric treatment supplements: 1) low protein (LP), 13% CP; 2) moderate protein (MP), 25% CP; and 3) high protein (HP), 39% CP. In Exp. 2, 15 ruminally and 12 esophageally cannulated steers (avg wt = 319 and 355 kg, respectively) were assigned randomly to LP, MP and HP treatments and were used in a 22-d winter grazing trial to evaluate forage intake and utilization characteristics. In Exp. 1, cow body condition (BC) and BW changes responded in linear (P less than .01) and quadratic (P less than .01) fashions to increasing protein concentration, with MP and HP displaying the least BC and BW loss from trial initiation (d 1) through d 84. From d 84 to calving (avg calving date = d 120), only the HP supplement continued to be effective in minimizing BC loss (P less than .01). Calf birth weight tended (P = .17) to increase in a linear fashion to increasing supplemental protein concentration, but calf ADG and cow reproductive efficiency were unaffected (P greater than .10). In Exp. 2, forage OM intake responded in a quadratic fashion (P less than .10), with the MP treatment having the highest NDF digestibility and ruminal OM fill. In conclusion, beef cow BC and BW losses during the winter grazing period were minimized with increasing supplemental CP concentration. Intake and utilization of dormant forage by steers were improved with moderate (26%) levels of CP in the supplement. PMID- 2312441 TI - Sulfur and nitrogen metabolism in the bovine fed different forms of supplemental sulfur. AB - Twelve growing Angus heifers averaging 282 kg in weight were fed a tall fescue hay-based diet in a completely randomized design experiment to determine sulfur (S) and nitrogen (N) metabolism and bioavailability of different forms of supplemental S:elemental S (E), sodium sulfate (SU) and DL-methionine (M). The study included a 72-h adaptation phase that was followed immediately by a 5-d retention phase. Control (C) heifers were fed a ground fescue hay diet twice daily throughout the study. Supplementation with .15% S from E, SU or M to the basal diet began at h 0. Differences in total blood S, plasma S and ruminal NH3 N were dependent on sampling time in the 72-h adaptation phase. Urinary S excretion during 0 to 72 h was greater for S-supplemented calves than for C. Mean molar proportions of acetate, butyrate, isobutyrate and valerate were affected by form of S supplementation. No treatment differences (P greater than .10) were noted in total VFA concentrations. Sulfur supplementation increased daily urinary sulfate (P less than .01), total urinary S (P less than .01) and fecal S (P less than .01) excretion during the retention phase. Methionine and SU heifers had the greatest urinary S losses, and fecal S was highest for E (P less than .01). No differences (P greater than .10) in DM digestion occurred among treatments. N retention (g/d) and N retention as a percentage of intake averaged 5.9, 8.5; 13.2, 18.7; 13.8, 20.5; and 11.3, 19.2, respectively, for C, E, SU and M. Sulfur retention (g/d) was increased (P less than .10) by S supplementation. Sulfur supplementation of a basal fescue hay diet increased S retention transitorily, although much of the added S was lost through excretory routes. Supplementing S as E, SU or M appeared to be equally beneficial, despite differences in route and extent of S excretion among the three S sources. PMID- 2312442 TI - Simultaneous isolation and characterization of brush border and basolateral membrane vesicles from bovine small intestine. AB - Purified brush border and basolateral membranes were isolated from homogenized intestinal enterocytes of Holstein steers by divalent cation precipitation followed by differential and sucrose density gradient centrifugation. Alkaline phosphatase and Na/K adenosine triphosphatase served as marker enzymes for the brush border and basolateral membranes, respectively. The brush border and basolateral membrane fractions were enriched 5.1- and 10.1-fold, respectively, over the cellular homogenate. Electron micrographs, obtained with transmission electron microscopy, confirmed the vesicular nature of the membranes and revealed that basolateral membrane vesicles generally were smaller and more irregular in shape than brush border membrane vesicles. The vesicular nature of isolated membrane preparations was confirmed with osmotic activity experiments. Enrichment of brush border and basolateral membrane fractions compared to the initial homogenate and the vesicular configuration of both preparations indicate that the isolated brush border and basolateral membrane preparations were suitable models for evaluating nutrient transport properties of bovine small intestine. The number of transport experiments possible per animal using the membrane vesicle technique is many times more efficient than some other in vitro techniques (i.e., intestinal rings or everted sacs). PMID- 2312443 TI - Pharmacokinetics of sodium fusidate after single and repeated infusions and oral administration of a new formulation. AB - The pharmacokinetics of sodium fusidate were studied in eight healthy volunteers (five males and three females) aged 21 to 33 years (29.1 +/- 1.5), weight 46 to 79 kg (61.6 +/- 4.0 kg). First, the subjects were given 500 mg of sodium fusidate by infusion over two hours; secondly, one month later, the volunteers were given 500 mg of fusidate by infusion every eight hours for three days; thirdly, two 250 mg tablets of a new film coated formulation were administered as a single dose. Plasma concentrations of fusidate were measured by HPLC. Peak plasma concentrations reached at the end of the first and the last infusions were 52 +/- 5 mg/l and 123 +/- 12 mg/l respectively. The following mean pharmacokinetic parameters were obtained after single intravenous administration: elimination half-life 10 +/- 1 h, total clearance 22 +/- 2 ml/min and volume of distribution 0.30 +/- 0.04 l/kg. After repeated administration the half-life and the volume of distribution remained unchanged whereas total clearance was halved (11 +/- 1 ml/min). This leads to an experimental accumulation ratio (3.6 +/- 0.2) higher than the theoretical one (1.8 +/- 0.1; P less than 0.01). Consequently, mean trough and peak steady state plasma concentrations (81 +/- 9 and 123 +/- 12 mg/l respectively) are higher than those expected from the single dose kinetics (33 +/ 4 and 76 +/- 7 mg/l respectively). This dose regimen leads to concentrations well above the MIC for most sensitive strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312444 TI - Staphylococcal bacteraemia and endocarditis and fusidic acid. AB - In 1980, we reported an association between the use of fusidic acid (particularly the intravenous formulation) and jaundice in patients who had received the drug for the treatment of Staphylococcus aureus bacteraemia during the previous 10 years. We have continued to use fusidic acid for severe staphylococcal infections, but have recommended oral administration whenever possible. In the earlier study the incidence of jaundice in patients given intravenous fusidic acid was 48%, but in the recent study of 145 patients it was 17%. Whereas 71% of patients receiving fusidic acid in the earlier series were given the intravenous drug (with or without oral) only 25% of patients were given the intravenous drug in the recent series. The incidence of jaundice in those patients treated only with the oral formulation was 13% in the earlier study and 6% in the recent study. Although jaundice was usually reversible, it is nevertheless an unwanted side effect. Resistance of S. aureus to fusidic acid remains at around 1%; it may be present on primary isolation or arise during treatment. This seems to occur particularly in patients with endocarditis or bone infection despite the use of fusidic acid in combination with another antibiotic. After some 25 years of clinical use, fusidic acid remains a most useful anti-staphylococcal antibiotic; the intravenous preparation should be avoided when possible. PMID- 2312446 TI - Susceptibility to fusidic acid among Danish Staphylococcus aureus strains and fusidic acid consumption. AB - A total of 8176 Danish Staphylococcus aureus strains isolated from cases of bacteraemia during the years 1963 to 1987 were investigated for resistance to fusidic acid. During the whole period 1% of the strains or less were resistant (MIC of 2 mg/l or more). The total Danish consumption of fusidic acid during the same period increased from 0.008 to 0.029 defined daily doses/1000 inhabitants/day. The resistant strains were mainly sporadic isolates with the phage-types and antibiotic-resistance patterns predominant in Denmark at the time of their isolation. PMID- 2312445 TI - Clinical experiences with fusidic acid in cystic fibrosis patients. AB - A survey of Staphylococcus aureus lung infection in 243 patients with cystic fibrosis (CF) was conducted between 1986 and 1988. A total of 217 patients (89%) received 1605 courses of anti-staphylococcal therapy given during this period. The majority of courses comprised combined therapy with two anti-staphylococcal drugs. The combination of dicloxacillin and fusidic acid was employed most frequently. Some patients were given other anti-staphylococcal regimens, because of penicillin allergy (14 cases) or dyspeptic side effects with fusidic acid (21 patients). A small but significant increase in precipitins against S. aureus was observed during the study period. Bacterial resistance to the anti-staphylococcal drugs used remained at a low level (strains resistant to methicillin less than 0.1%, strains resistant to fusidic acid 1.2%). When the isolates were compared with 56,140 strains of S. aureus isolated from non-CF patients hospitalized in Denmark over the same period, no differences in phagetypes or in antibiotic resistance were seen, indicating that selection of strains and cross infection do not seem to be a major problem in CF patients. PMID- 2312447 TI - Mechanism for increase in tracheobronchial blood flow induced by hyperventilation of dry air in dogs. AB - To test whether the consistent increase in tracheal and bronchial blood flow observed in dogs during hyperventilation of dry air might be the result of release of mediators such as vasodilatory prostaglandins or neuropeptides, we studied two groups of anesthetized mechanically ventilated dogs. Group 1 (n = 6) was hyperventilated for four 30-min periods with 1) warm humid air (38-40 degrees C, 100% relative humidity), 2) warm dry air (38-40 degrees C, 0% relative humidity), 3) warm humid air, and 4) warm dry air. After period 2, a loading dose of indomethacin (4 mg/kg iv) was given over 15 min followed by a constant infusion (4 mg.kg-1.h-1). Group 2 (n = 10) was hyperventilated for four 15- to 20 min periods by use of the protocol described above. After period 3 (group 2a) or period 2 (group 2b), topical 4% lidocaine hydrochloride solution was instilled into the trachea and main stem bronchi. Five minutes before the end of each period of hyperventilation, cardiac output and vascular pressures were measured. To determine airway blood flow, differently labeled radioactive microspheres were injected into the left atrium. After the last measurements, dogs were killed and the lungs excised. Blood flow to the trachea, main stem bronchi, and parenchyma (group 1 only) was calculated. Results showed that hyperventilation of dry air produced a significant increase in blood flow to the trachea and bronchi (period 2). In group 1, this increase was attenuated (P less than 0.02) after administration of indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312448 TI - Muscle mitochondrial ultrastructure in exercise-trained iron-deficient rats. AB - To investigate effects of endurance training and iron deficiency, as well as the combination of these two conditions, on mitochondrial ultrastructure, weanling rats at 3 wk of age were assigned to iron-deficient (Fe-) and iron-sufficient (Fe+) groups. Subsequently, groups were subdivided into exercise-trained (T) and sedentary (S) groups. Electron microscopy showed subsarcolemmal and intrafibrillar mitochondria in the Fe-T animals to be enlarged with sparse cristae and vacuole-like areas compared with the other groups. An increase in the number of lipid droplets in both Fe- groups was observed. Stereological measurements revealed a 99% increase in the volume occupied by muscle mitochondria in the Fe-T animals (11.9 +/- 0.8%) over the Fe+T (5.9 +/- 0.4%) and Fe+S (6.0 +/- 0.3%) groups and a 55% increase over the Fe-S groups (7.7 +/- 0.3%). The ratio of mitochondrial surface area to tissue volume was significantly decreased only in the Fe-T group. These results indicate that the combined stresses of iron deficiency and training produce mitochondrial ultrastructural changes far greater than those of iron deficiency or training alone. Because this is also the case with the disproportion among mitochondrial enzymes, it is possible that the ultrastructural changes are indicative of morphological responses that maintain ATP turnover during exercise in iron deficiency when oxygen transport and electron transport chain activities are reduced. PMID- 2312449 TI - Enhancement of arm exercise endurance capacity with dihydroxyacetone and pyruvate. AB - The effects of dietary supplementation of dihydroxyacetone and pyruvate (DHAP) on endurance capacity and metabolic responses during arm exercise were determined in 10 untrained males (20-26 yr). Subjects performed arm ergometer exercise (60% peak O2 consumption) to exhaustion after consumption of standard diets (55% carbohydrate, 15% protein, 30% fat; 35 kcal/kg) containing either 100 g of Polycose (placebo, P) or DHAP (3:1, treatment) substituted for a portion of carbohydrate. The two diets were administered in a random order, and each was consumed for a 7-day period. Biopsy of the triceps muscle was obtained immediately before and after exercise. Blood samples were drawn through radial artery and axillary vein catheters at rest, after 60 min of exercise, and at exercise termination. Arm endurance was 133 +/- 20 min after P and 160 +/- 22 min after DHAP (P less than 0.01). Triceps glycogen at rest was 88 +/- 8 (P) and 130 +/- 19 mmol/kg (DHAP) (P less than 0.05). Whole arm arteriovenous glucose difference (mmol/l) was greater (P less than 0.05) for DHAP than P at rest (0.60 +/- 0.12 vs. 0.05 +/- 0.09) and after 60 min of exercise (1.00 +/- 0.12 vs. 0.36 +/- 0.11), but it did not differ at exhaustion. Neither respiratory exchange ratio nor respiratory quotient differed between trials at rest, after 60 min of exercise, or at exhaustion. Plasma free fatty acid, glycerol, beta hydroxybutyrate, catecholamines, and insulin were similar during rest and exercise for both diets. Feeding DHAP for 7 days increased arm muscle glucose extraction before and during exercise, thereby enhancing submaximal arm endurance capacity. PMID- 2312450 TI - Bronchial circulation in pulmonary artery occlusion and reperfusion. AB - Obstruction of pulmonary arterial blood flow results in minimal biochemical and/or morphological changes in the involved lung. If the lung is reperfused, a syndrome of leukopenia and lung edema occurs. We used the radiolabeled microsphere technique to measure the response of the bronchial circulation in rabbits to acute pulmonary artery occlusion (PAO) and to pulmonary artery reperfusion. We found that the bronchial blood flow (Qbr) decreased from a base line of 0.37 +/- 0.10 to 0.09 +/- 0.04 (SE) ml.min-1.g dry lung-1 (P less than or equal to 0.05) after 4 h of PAO. In a separate group of animals, Qbr 24 h after PAO remained low (0.20 +/- 0.07 ml.min-1.g dry lung-1, P = 0.06). Qbr during PAO was inversely correlated with the wet-to-dry ratio after reperfusion (r = -0.68, P = 0.06). Qbr did not change during 4 h of reperfusion. We speculate that a critical level of Qbr may be necessary during PAO to prevent ischemia/reperfusion injury from occurring. PMID- 2312451 TI - Bone growth and calcium balance during simulated weightlessness in the rat. AB - Rats, age 28 days, experiencing tail suspension in modified metabolic cages for 1, 2, and 3 wk were compared with littermate controls. Food and water consumption, urinary and fecal Ca excretion, and serum Ca were measured; hearts, fore- and hindlimb bones, skulls, and mandibles were removed for determination of wet, dry, and ash weights and Ca concentration and for histological examination. Weight gain and Ca intake and excretion were the same for both groups; both displayed net Ca gain. Suspended rats had significantly lower wet, dry, and ash weights of femora and tibiae. Dry weights of the humeri and radii/ulnae were moderately higher, and the skull and mandible dry and ash weights were significantly higher in suspended than in control rats. Cortical thickness of the femur, but not humerus, was less in suspended rats. The data are consistent with the hypothesis that bone growth is influenced by the cardiovascular changes associated with tail suspension. PMID- 2312452 TI - Bone mechanical properties after exercise training in young and old rats. AB - The effects of a 10-wk training regimen on the mechanical properties of the femur and humerus were evaluated in 2.5- and 25-mo-old Fischer 344 female rats. The rats trained on a rodent treadmill 5 days/wk for 10 wk. Duration, grade, and speed increased until the rats maintained 1 h/day at 15% grade and either 15 m/min (old rats) or 36 m/min (young rats). Excised bones were mechanically tested with a 3-point flexure test for mechanical properties of force, stress, and strain. Fat-free dry weight (FFW) and moment of inertia were also obtained. With aging, similar increases were observed in both the femur and humerus for FFW, moment of inertia, and force. Ultimate stress was reduced in the senescent femur while strain was elevated; a similar but nonsignificant trend was observed in the humerus. Irrespective of age, training increased FFW in the femur and, to a lesser degree, in the humerus. Breaking force was elevated for both bones after training. In young and old bones, the training-induced differences in bone mass and force were similar, despite differences in training intensity. In the old trained rats, femur ultimate stress was greater than that in control rat femurs and similar to that in young rat femurs. The results of the present study indicate that training effects were not limited by age. PMID- 2312453 TI - Assessment of cardiovascular reflexes: influence of posture and period of preceding rest. AB - The aim of the present study was to investigate the effects of a pretest redistribution of blood volume and of a change in the neurohumoral condition on the blood pressure (BP) and heart rate (HR) responses to three commonly used cardiovascular reflex tests: standing up, forced breathing, and the Valsalva maneuver in 10 healthy male subjects. Base-line conditions were altered by changing posture and the duration of rest preceding the test stimulus. A continuous recording of finger BP was obtained noninvasively by a Finapres. The main observations from this study are with respect to standing up: lengthening the period of preceding rest from 1 to 20 min enlarges the initial BP (systolic/diastolic) decrease (from 8 +/- 10/9 +/- 4 to 27 +/- 8/19 +/- 4 mmHg, P less than 0.01) and the subsequent BP overshoot (from 17 +/- 10/12 +/- 7 to 31 +/ 10/18 +/- 7 mmHg, P less than 0.05); to forced breathing: inspiratory-expiratory changes in BP but not in HR are larger in the upright posture (P less than 0.05); and to the Valsalva maneuver: change in posture from supine to standing increases the phase II BP decrease (from 18 +/- 12/8 +/- 6 to 45 +/- 16/21 +/- 9 mmHg), phase IV systolic BP overshoot (from 26 +/- 16 to 71 +/- 17 mmHg), delta HRmax (from 30 +/- 10 to 47 +/- 12 beats/min), and the Valsalva ratio (HRmax/HRmin), from 2.0 +/- 0.3 to 2.6 +/- 0.7, all significant at P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312454 TI - Responses to negative pressure surrounding the neck in anesthetized animals. AB - Continuous positive pressure applied at the nose has been shown to cause a decrease in upper airway resistance. The present study was designed to determine whether a similar positive transmural pressure gradient, generated by applying a negative pressure at the body surface around the neck, altered upper airway patency. Studies were performed in nine spontaneously breathing anesthetized supine dogs. Airflow was measured with a pneumotachograph mounted on an airtight muzzle placed over the nose and mouth of each animal. Upper airway pressure was measured as the differential pressure between the extrathoracic trachea and the inside of the muzzle. Upper airway resistance was monitored as an index of airway patency. Negative pressure (-2 to -20 cmH2O) was applied around the neck by using a cuirass extending from the jaw to the thorax. In each animal, increasingly negative pressures were transmitted to the airway wall in a progressive, although not linear, fashion. Decreasing the pressure produced a progressive fall in upper airway resistance, without causing a significant change in respiratory drive or respiratory timing. At -5 cmH2O pressure, there occurred a significant fall in upper airway resistance, comparable with the response of a single, intravenous injection of sodium cyanide (0.5-3.0 mg), a respiratory stimulant that produces substantial increases in respiratory drive. We conclude that upper airway resistance is influenced by the transmural pressure across the airway wall and that such a gradient can be accomplished by making the extraluminal pressure more negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312456 TI - Startle-evoked changes in diaphragmatic activity during wakefulness and sleep. AB - Tonic inhibition of some respiratory muscles occurs as part of the generalized muscle atonia of rapid-eye-movement sleep (REMS). A second type of inhibition of the diaphragm during REMS, fractionations, consists of brief pauses in the diaphragmatic electromyogram (DIA EMG) in association with phasic events. Because motor inhibition can occur as part of the startle response, and the brain is highly activated during REMS, we hypothesized that the neural basis of the fractionations might be activation of a startle network. To test this hypothesis, tone bursts (100 dB, 20-ms duration at 15-s intervals) were applied to cats at a fixed inspiratory level in the DIA moving average during REMS, non-rapid-eye movement sleep (NREMS), and wakefulness. Parallel sham studies (no tone applied) were obtained for each state. The response of the DIA EMG was averaged over 100 ms by using the tone pulse as a trigger, and the following parameters of the DIA EMG were measured: latency to peak and/or nadir, increment or decrement in activity, and duration of peak and/or nadir. After a tone, all five animals studied displayed a profound suppression of DIA activity during REMS (latency to nadir 42.4 +/- 10.0 ms, duration of suppression 35.9 +/- 17.6 ms). Similarly, DIA activity was suppressed in all cats during NREMS (latency to nadir 40.9 +/- 13.3 ms, duration 23.9 +/- 13.4 ms). An excitatory response was observed in only two cats during NREMS and wakefulness. The similarity of startle-induced DIA EMG pauses to spontaneous fractionations of DIA activity during REMS suggests that the latter result from activation of a central startle system. PMID- 2312457 TI - Ventilatory effects of high and pulsatile blood flow in the pulmonary circulation. AB - The mechanism of ventilatory stimulation that accompanies increases in cardiac output is unknown. Previous studies addressing this issue have been inconclusive. However, only steady pulmonary blood flow was used. The effect of flow pulsatility merits consideration, because increasing cardiac output raises not only mean pulmonary arterial pressure but also pulse pressure; mechanoreceptors with an important dynamic component to their responses may cause a response to pulsatile, but not steady, flow. Studies were done on anesthetized cats (n = 4) and dogs (n = 4). The right pulmonary artery was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the right pulmonary artery. The right pulmonary circulation was perfused at different levels of flow, which was either steady or pulsatile. Steady-state flow of up to 150 ml.kg-1.min-1 (270 ml.kg-1.min-1 when corrected for the proportion of lung tissue perfused) did not affect breathing pattern. When high pulmonary flow was made pulsatile (pulse pressure approximately 23 mmHg), breath duration decreased from 3.7 +/- 0.72 to 3.4 +/- 0.81 (SD) s (P less than 0.01), representing a change in frequency of only 9%. There was no change in peak inspiratory activity. It was concluded that pulmonary vascular mechanoreceptors are not likely to contribute significantly to the increase in ventilation in association with increases in cardiac output. PMID- 2312458 TI - Changes in airway length after unilateral pneumonectomy in weanling ferrets. AB - We have previously shown that airway cross-sectional area increases 15-20% after pneumonectomy in weanling ferrets by measuring bronchial casts. We have now reanalyzed these same casts to quantitate changes in airway length after pneumonectomy. In each cast the distance from each of 120 airways to the terminal bronchiole along its axial pathway was measured. The relationship between the logarithm of this distance and that of the fraction of the lobe subtended by an airway could be described by a quadratic equation with a correlation coefficient greater than 0.85. Subsegmental and more distal airways of postpneumonectomy animals were 33-47% longer than those of controls. Overall the main axial pathway of airways in the left lower lobes was 12% longer in operated animals, but this increase was primarily accounted for by an increase in the length of the more peripheral airways. Central airways were little if any longer in operated animals. After pneumonectomy in weanling ferrets, subsegmental and peripheral airway lengths increase to a greater degree than lung volume and airway cross sectional area, whereas central airway lengths increase to a lesser extent if at all. The mechanisms responsible for this difference between central and intralobar compensatory airway growth are unknown. PMID- 2312455 TI - Activation of branched-chain alpha-keto acid dehydrogenase complex by exercise: effect of high-fat diet intake. AB - The effect of exercise on the activity of branched-chain alpha-keto acid dehydrogenase complex in liver and muscle was studied in rats fed a high-fat (FAT) or a high-carbohydrate (CHO) diet. Both diet groups of rats were offered isoenergetic diets by a meal-feeding method and were trained by treadmill running. On the final day of the experiment, half of the rats in each diet group were exercised by 2 h of running just before they were killed. The activity state of the enzyme complex was elevated maximally by exercise in liver of rats fed the FAT diet but not in liver of rats fed the CHO diet, suggesting that catabolism of branched-chain amino acids in rat liver during exercise was enhanced by the FAT diet. The activity state of the enzyme complex in muscle was enhanced by exercise in both groups of rats, but a significant difference was not observed between the groups. The concentration of branched-chain amino acids was elevated in liver and muscle by exercise in both groups of rats, but the elevated levels in liver were lower in rats fed the FAT diet than in those fed the CHO diet. Serum branched chain amino acid concentrations were significantly lower in rested rats fed the FAT diet than in those fed the CHO diet, and the leucine and isoleucine concentrations in the former were elevated by exercise, but the serum concentrations in the latter were not significantly affected by exercise. ATP and ADP concentrations in muscle were not significantly affected by either diet or exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312459 TI - Skeletal muscle plasma membrane glucose transport and glucose transporters after exercise. AB - Recent reports have shown that immediately after an acute bout of exercise the glucose transport system of rat skeletal muscle plasma membranes is characterized by an increase in both glucose transporter number and intrinsic activity. To determine the duration of the exercise response we examined the time course of these changes after completion of a single bout of exercise. Male rats were exercised on a treadmill for 1 h (20 m/min, 10% grade) or allowed to remain sedentary. Rats were killed either immediately or 0.5 or 2 h after exercise, and red gastrocnemius muscle was used for the preparation of plasma membranes. Plasma membrane glucose transporter number was elevated 1.8- and 1.6-fold immediately and 30 min after exercise, although facilitated D-glucose transport in plasma membrane vesicles was elevated 4- and 1.8-fold immediately and 30 min after exercise, respectively. By 2 h after exercise both glucose transporter number and transport activity had returned to nonexercised control values. Additional experiments measuring glucose uptake in perfused hindquarter muscle produced similar results. We conclude that the reversal of the increase in glucose uptake by hindquarter skeletal muscle after exercise is correlated with a reversal of the increase in the glucose transporter number and activity in the plasma membrane. The time course of the transport-to-transporter ratio suggests that the intrinsic activity response reverses more rapidly than that involving transporter number. PMID- 2312460 TI - Modulation of lymphatic pumping by lymph-borne factors after endotoxin administration in sheep. AB - The purpose of this study was to test the hypothesis that endotoxin administration to sheep results in host-derived lymph-borne factors that modulate lymphatic pumping activity. To achieve this, two sheep were used for each experiment. In the test animal, a segment of intestinal lymphatic was isolated from all lymph input and provided with lymph from a reservoir. Pumping activity was initiated with a fixed transmural pressure applied to the test vessel, and the only input to this duct was provided by lymph from an indwelling catheter in a second donor sheep. The intravenous administration of endotoxin to the donor animals (33 micrograms/kg) generally resulted in increased pumping in the test vessels over the 1st h, but this was followed by reductions in pumping until flow stopped in all preparations. In control experiments (no endotoxin administered) pumping was unaffected. Further investigation revealed that these activities were relatively unstable and, in the case of the inhibitory material, appeared to act by decreasing the sensitivity of the vessel to changes in transmural pressure, because flow could be reestablished in the test vessels by elevating transmural pressures above the level originally chosen for the experiment. Endotoxin itself had no direct effect on sheep lymphatics in vivo or on bovine lymphatic vessels in vitro. However, the appearance of erythrocyte hemolysate (erythrolysate) in lymph was regularly observed after endotoxin infusion, and we demonstrated that erythrolysate (diluted to contain 10(-5) M hemoglobin) was a potent inhibitor of lymphatic pumping in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312461 TI - Tracheal smooth muscle mechanics in vivo. AB - We applied the technique of sonomicrometry to directly measure length changes of the trachealis muscle in vivo. Pairs of small 1-mm piezoelectric transducers were placed in parallel with the muscle fibers in the posterior tracheal wall in seven anesthetized dogs. Length changes were recorded during mechanical ventilation and during complete pressure-volume curves of the lung. The trachealis muscle showed spontaneous fluctuations in base-line length that disappeared after vagotomy. Before vagotomy passive pressure-length curves showed marked hysteresis and length changed by 18.5 +/- 13.2% (SD) resting length at functional residual capacity (LFRC) from FRC to total lung capacity (TLC) and by 28.2 +/- 16.2% LFRC from FRC to residual volume (RV). After vagotomy hysteresis decreased considerably and length now changed by 10.4 +/- 3.7% LFRC from FRC to TLC and by 32.5 +/- 14.6% LFRC from FRC to RV. Bilateral supramaximal vagal stimulation produced a mean maximal active shortening of 28.8 +/- 14.2% resting length at any lung volume (LR) and shortening decreased at lengths above FRC. The mean maximal velocity of shortening was 4.2 +/- 3.9% LR.S-1. We conclude that sonomicrometry may be used to record smooth muscle length in vivo. Vagal tone strongly influences passive length change. In vivo active shortening and velocity of shortening are less than in vitro, implying that there are significant loads impeding shortening in vivo. PMID- 2312462 TI - Effects of allopurinol on smoke inhalation in the ovine model. AB - We hypothesized that the pulmonary damage induced by smoke inhalation is the result of ischemic reperfusion injury. We determined the effect of allopurinol (xanthine oxidase inhibitor) on the pulmonary microvascular fluid flux in an ovine model after inhalation of cotton smoke (n = 13) and compared these data with those from untreated similarly smoke-injured (n = 7), as well as sham- (air, n = 9) smoked, animals and sheep given an equivalent dose of CO (n = 7). Smoke injury resulted in an increased lung lymph flow, lymph-to-plasma protein ratio, lung content of polymorphonuclear cells, and extravascular lung water (gravametric), in addition to histological evidence of tissue (pulmonary) edema and destruction. No significant difference was found in these variables between the sheep that were injured with smoke whether or not they were pretreated with allopurinol. The sham-smoked and CO-insufflated animals showed no significant changes in cardiopulmonary function or morphology. We conclude that there are few data to support a role of ischemic reperfusion injury in the pulmonary damage seen after smoke inhalation. PMID- 2312463 TI - Effects of phorbol myristate acetate-stimulated human leukocytes on rat lung. AB - Human blood was separated into polymorphonuclear (PMN) and mononuclear (MN) leukocyte fractions, and 3 x 10(7) cells (PMN or MN) were added to isolated rat lungs perfused with 5% human albumin in buffer and stimulated with phorbol myristate acetate (PMA). Lungs perfused with either albumin alone, PMN, or MN but not stimulated with PMA showed no change in vascular resistance or endothelial permeability measured as the capillary filtration coefficient (Kf,c). Lungs that were stimulated with PMA with no cells showed no change in Kf,c (0.34 +/- 0.07 vs. 0.37 +/- 0.7), but vascular resistance increased in all segments of the circulation. Capillary pressure, the major force responsible for edema formation, nearly doubled in the absence of cells 40 min after PMA. Lungs perfused with either PMN or MN and stimulated with PMA were injured. Kf,c increased from 0.41 +/- 0.03 to 0.87 +/- 0.10 (PMN) and from 0.36 +/- 0.07 to 0.81 +/- 0.23 (MN) 90 min after PMA. In addition to the increased endothelial permeability, vascular resistances and pressures also increased in the cell-perfused PMA-stimulated lungs. These results demonstrate that cells other than granulocytes are capable of producing severe acute lung injury and cannot be ignored when the effects of PMA on neutrophil-depleted lungs are studied. PMID- 2312464 TI - Oxygen consumption and distribution of blood flow in rats climbing a laddermill. AB - The purpose of this study was threefold: 1) to determine whether untrained rats that refused to run on treadmill would climb on a laddermill (75 degrees incline); 2) to determine O2 consumption (VO2) in untrained rats as a function of laddermill climbing speed; and 3) to determine whether the circulatory response of untrained rats to laddermill climbing is similar to that previously reported for treadmill running at an equivalent VO2. Eighteen female Sprague-Dawley rats that would not perform on a treadmill as part of another study were used to measure VO2 as a function of laddermill speed (5-17 m/min). Data were obtained from all 18 rats; VO2 increased linearly as a function of laddermill speed (r = 0.83, y = 3.0 x + 63.2). Twenty-four female Sprague-Dawley rats that also refused to run on a treadmill were used to measure mean arterial pressure, heart rate, and blood flow distribution (with microspheres) during climbing at 5 and 10 m/min. These exercise intensities were metabolically equivalent to level treadmill running at 45 and 60 m/min (VO2 approximately 78 and 93 ml.min-1.kg-1, respectively). Of the 24 animals, 23 were willing to climb. Mean arterial pressures were higher (approximately 10%) during laddermill climbing than during equivalent treadmill running, but heart rates were the same. General blood flow distribution among muscles as a function of fiber type (with red muscles receiving higher flows) and between muscles and visceral tissues (muscle blood flow increased as a function of exercise intensity while visceral blood flows decreased) were similar to data for rats running on the level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312465 TI - Time-dependent changes in cardiovascular regulation caused by chronic tobacco smoke exposure. AB - The purpose of this study was to determine whether chronic tobacco smoke exposure for less than 2 mo alters cardiovascular regulation. One group of male Sprague Dawley rats was administered tobacco smoke from low-nicotine cigarettes (group A, 1 mg/cigarette) for 4-6 wk, while a second group (B) served as a sham control by receiving only puffs of room air. Reflex adjustments in mean arterial blood pressure (MAP) after bilateral common carotid occlusion (BCCO) were compared between the two groups. In the anesthetized control state, no significant difference existed for the cardiovascular parameters measured in the two groups. However, MAP increases after BCCO were significantly greater in the smoke-treated animals (P less than 0.05) compared with the sham-treated group. At 10, 20, 30, and 40 s after BCCO, MAP increases above preocclusion values were 66, 45, 42, and 38% for group A and 35, 26, 24, and 22% for group B, respectively. Additionally, the time required to reach maximum MAP after BCCO was significantly less (P less than 0.05) for the smoke-treated vs. sham-treated animals (8.5 +/- 0.2s for group A, 11.2 +/- 0.3s for group B). MAP changes during BCCO were significantly different (P less than 0.05) between the treatment groups after cervical vagotomy. It is concluded that chronic tobacco smoke exposure in experimental animals for periods as short as 4-6 wk alters the reflex regulation of the cardiovascular system. PMID- 2312466 TI - Does leukotriene C4 mediate hypoxic vasoconstriction in isolated ferret lungs? AB - To evaluate leukotriene (LT) C4 as a mediator of hypoxic pulmonary vasoconstriction, we examined the effects of FPL55712, a putative LT antagonist, and indomethacin, a cyclooxygenase inhibitor, on vasopressor responses to LTC4 and hypoxia (inspired O2 tension = 25 Torr) in isolated ferret lungs perfused with a constant flow (50 ml.kg-1.min-1). Pulmonary arterial injections of LTC4 caused dose-related increases in pulmonary arterial pressure during perfusion with physiological salt solution containing Ficoll (4 g/dl). FPL55712 caused concentration-related inhibition of the pressor response to LTC4 (0.6 micrograms). Although 10 micrograms/ml FPL55712 inhibited the LTC4 pressor response by 61%, it did not alter the response to hypoxia. At 100 microgram/ml, FPL55712 inhibited the responses to LTC4 and hypoxia by 73 and 71%, respectively, but also attenuated the vasoconstrictor responses to prostaglandin F2 alpha (78% at 8 micrograms), phenylephrine (68% at 100 micrograms), and KCl (51% at 40 mM). At 0.5 microgram/ml, indomethacin significantly attenuated the pressor response to arachidonic acid but did not alter responses to LTC4 or hypoxia. These results suggest that in isolated ferret lungs 1) the vasoconstrictor response to LTC4 did not depend on release of cyclooxygenase products and 2) LTC4 did not mediate hypoxic vasoconstriction. PMID- 2312467 TI - Fatigue of single motor units in human masseter. AB - The spike-triggered averaging technique was used to determine the time course and extent of fatigue of single motor unit twitches in the human masseter. This is the first report of a fatigue test having been applied to masseter motor units in either animals or humans. The human masseter was found to be comprised predominantly of fast-twitch motor units with a broad spectrum of fatigability. Very few physiological type S units were found, despite histochemical evidence for a substantial population of type I fibers in the masseter. In addition, there was no significant correlation between fatigability and either twitch amplitude or contractile speed in the motor units studied. The latter observations are consistent with the unusual histological features of the masseter. Comparison with other human fatigue data suggests that the extent of fatigue in the present population of masseter motor units after approximately 3,000 activations is similar to that reported for populations of units in first dorsal interosseous and medial gastrocnemius. PMID- 2312468 TI - Interaction between concurrent strength and endurance training. AB - To assess the effects of concurrent strength (S) and endurance (E) training on S and E development, one group (4 young men and 4 young women) trained one leg for S and the other leg for S and E (S+E). A second group (4 men, 4 women) trained one leg for E and the other leg for E and S (E+S). E training consisted of five 3 min bouts on a cycle ergometer at a power output corresponding to that requiring 90-100% of oxygen uptake during maximal exercise (VO2 max). S training consisted of six sets of 15-20 repetitions with the heaviest possible weight on a leg press (combined hip and knee extension) weight machine. Training was done 3 days/wk for 22 wk. Needle biopsy samples from vastus lateralis were taken before and after training and were examined for histochemical, biochemical, and ultrastructural adaptations. The nominal S and E training programs were "hybrids", having more similarities as training stimuli than differences; thus S made increases (P less than 0.05) similar to those of S+E in E-related measures of VO2max (S, S+E: 8%, 8%), repetitions with the pretraining maximal single leg press lift [1 repetition maximum (RM)] (27%, 24%), and percent of slow-twitch fibers (15%, 8%); and S made significant, although smaller, increases in repetitions with 80% 1 RM (81%, 152%) and citrate synthase (CS) activity (22%, 51%). Similarly, E increased knee extensor area [computed tomography (CT) scans] as much as E+S (14%, 21%) and made significant, although smaller, increases in leg press 1 RM (20%, 34%) and thigh girth (3.4%, 4.8%). When a presumably stronger stimulus for an adaptation was added to a weaker one, some additive effects occurred (i.e., increases in 1 RM and thigh girth that were greater in E+S than E; increases in CS activity and repetitions with 80% 1 RM that were greater in S+E than S). When a weaker, although effective, stimulus was added to a stronger one, addition generally did not occur. Concurrent S and E training did not interfere with S or E development in comparison to S or E training alone. PMID- 2312469 TI - Rate of disappearance of glycerol from plasma of fetal and newborn sheep. AB - The disappearance of glycerol from plasma was studied after a single intravenous injection to estimate its volume of distribution (Vdist), plasma clearance rate, and rate constant for irreversible loss (kd). Studies were repeated before and after birth of the lamb to test whether loss of the placenta could account for rapidly increasing plasma concentrations in the newborn. The disappearance of glycerol was closely described by a double-exponential model in each instance. In fetal sheep Vdist averaged 0.41 +/- 0.15 (SD) 1/kg fetal wt (n = 15). This volume decreased to 0.33 +/- 0.11 l/kg (n = 8) soon after functionally removing the placenta (by snaring the umbilical cord and maintaining the fetus with intrauterine ventilation), but the change was not significant. In newborn lambs 1 3 days of age, Vdist averaged 0.45 +/- 0.11 l/kg (n = 5, NS). Plasma clearance rate also did not change significantly, averaging 7.9 +/- 2.9, 7.9 +/- 3.8, and 9.0 +/- 5.9 ml.min-1.kg-1 in the fetus, after simulated birth, and in the newborn lamb, respectively, kd also was not altered measurably and averaged 0.020 +/- 0.006, 0.024 +/- 0.007, and 0.019 +/- 0.007 min-1 during the same time periods. Similar results were obtained by using three widely different amounts of infused glycerol. The results indicate that removal of glycerol does not depend on placental function to an appreciable extent. It is concluded that plasma glycerol concentration reflects principally glycerol turnover and, hence, lipolysis before and after birth. PMID- 2312470 TI - Solute concentrations of the pulmonary epithelial lining fluid of anesthetized rats. AB - Uncertainty persists concerning the best method of estimating the volume and solute concentrations of the pulmonary epithelial lining fluid (ELF) recovered during bronchoalveolar lavage (BAL). In the present study, measurements were made of the BAL-to-plasma concentration ratios of a variety of solutes in an anesthetized rat model. One minute after an intravenous injection of labeled Na+ and urea, 5 ml of isotonic mannitol, saline, or glucose were injected into the trachea and an initial aliquot of the BAL was immediately removed. Initial BAL-to plasma concentration ratios of urea, Na+, Cl-, Ca2+, and total protein were similar (ranging from 0.013 to 0.017) after BAL with mannitol, but albumin and transferrin ratios were approximately 60% lower and K+ ratios were five times greater. Lavage with saline yielded BAL-to-plasma urea concentration ratios similar to those obtained with mannitol lavage. The BAL-to-plasma specific activity of urea was about twice that of Na+, indicating that urea diffused into the ELF more rapidly than Na+ during the 70 s that elapsed between the time the radioactive urea and Na+ were injected into the circulation and the time when lavage was complete. Subsequent lavage samples also indicated that urea rapidly diffuses into the fluid-filled lungs. These experiments suggest that isotonic mannitol may be a useful solution for lavage, because it allows use of Na+ and perhaps Cl- as additional indicators of ELF dilution by BAL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312471 TI - Effects of timing of inspiratory occlusion on cerebral evoked potentials in humans. AB - Previous studies from these laboratories have shown that airway occlusion applied from the onset of inspiration or during midinspiration is associated with cerebral evoked potentials in human subjects. The hypothesis tested in the present study was that the more abrupt decrease in mouth pressure produced by midinspiratory occlusion will be associated with evoked potentials that have shorter peak latencies and greater peak amplitudes than those produced by occlusions from the onset of inspiration. The second objective of the present study was to determine whether there is bilateral projection of inputs from the respiratory system to the somatosensory cortex. Random presentation of 64 midinspiratory occlusions and 64 occlusions from the onset of inspiration was performed in eight subjects. The inspirations preceding the occlusions served as control. Evoked potentials were recorded from the scalp with electrode pairs Cz C3 and Cz-C4. Reaction time to each type of occlusion was measured from the burst in electromyogram activity produced by contraction of the muscles encircling the eye. Each type of inspiratory occlusion was associated with evoked potentials that could be recorded bilaterally. The peak amplitudes of the evoked potentials recorded over the right cerebral hemisphere were significantly greater than those recorded from the left side. The peak amplitude was greater and the peak latency shorter for the evoked potentials produced by the midinspiratory occlusions. The results are consistent with the hypothesis that afferents mediating these potentials are stimulated by added loads to breathing and project bilaterally to the somatosensory cortex in humans. PMID- 2312472 TI - Training-induced skeletal muscle adaptations are independent of systemic adaptations. AB - To isolate the peripheral adaptations to training, five normal subjects exercised the nondominant (ND) wrist flexors for 41 +/- 11 days, maintaining an exercise intensity below the threshold required for cardiovascular adaptations. Before and after training, intracellular pH and the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) were measured by 31P magnetic resonance spectroscopy. Also maximal O2 consumption (VO2 max), muscle mass, and forearm blood flow were determined by graded systemic exercise, magnetic resonance imaging, and venous occlusion plethysmography, respectively. Blood flow, Pi/PCr, and pH were measured in both forearms at rest and during submaximal wrist flexion at 5, 23, and 46 J/min. Training did not affect VO2 max, exercise blood flow, or muscle mass. Resting pH, Pi/PCr, and blood flow were also unchanged. After training, the ND forearm demonstrated significantly lower Pi/PCr at 23 and 46 J/min. Endurance, measured as the number of contractions to exhaustion, also was increased significantly (63%) after training in the ND forearm. We conclude that 1) forearm training results in a lower Pi/PCr at identical submaximal work loads; 2) this improvement is independent of changes in VO2 max, muscle mass, or limb blood flow; and 3) these differences are associated with improved endurance and may reflect improved oxidative capacity of skeletal muscle. PMID- 2312473 TI - Effect of caffeine on ventilatory responses to hypercapnia, hypoxia, and exercise in humans. AB - The effect of oral caffeine on resting ventilation (VE), ventilatory responsiveness to progressive hyperoxic hypercapnia (HCVR), isocapnic hypoxia (HVR), and moderate exercise (EVR) below the anaerobic threshold (AT) was examined in seven healthy adults. Ventilatory responses were measured under three conditions: control (C) and after ingestion of either 650 mg caffeine (CF) or placebo (P) in a double-blind randomized manner. None of the physiological variables of interest differed significantly for C and P conditions (P greater than 0.05). Caffeine levels during HCVR, HVR, and EVR were 69.5 +/- 11.8, 67.8 +/ 10.8, and 67.8 +/- 10.9 (SD) mumol/l, respectively (P greater than 0.05). Metabolic rate at rest and during exercise was significantly elevated during CF compared with P. An increase in VE from 7.4 +/- 2.5 (P) to 10.5 +/- 2.1 l/min (CF) (P less than 0.05) was associated with a decrease in end-tidal PCO2 from 39.1 +/- 2.7 (P) to 35.1 +/- 1.3 Torr (CF) (P less than 0.05). Caffeine increased the HCVR, HVR, and EVR slopes (mean increase: 28 +/- 8, 135 +/- 28, 14 +/- 5%, respectively) compared with P; P less than 0.05 for each response. Increases in resting ventilation, HCVR, and HVR slopes were associated with increases in tidal volume (VT), whereas the increase in EVR slope was accompanied by increases in both VT and respiratory frequency. Our results indicate that caffeine increases VE and chemosensitivity to CO2 inhalation, hypoxia, and CO2 production during exercise below the AT. PMID- 2312474 TI - Strength training and determinants of VO2max in older men. AB - The effects of strength training on maximal aerobic power (VO2max) and some of its determinants were studied in 12 healthy older men (60-72 yr). They underwent 12 wk of strength conditioning of extensors and flexors of each knee with eight repetitions per set, three sets per session, and three sessions per week at 80% of the one repetition maximum (1 RM). Left knee extensors showed a 107% increase in 1 RM, a 10% increase in isokinetic strength at 60 degrees/s, and a 23% increase in total work performed during 25 contractions on an isokinetic dynamometer. Strength measurements of the untrained left elbow extensors showed no change. Leg cycle ergometer VO2max per unit fat-free mass increased by an average 1.9 ml (P = 0.034) whereas arm cycle VO2max was unchanged. Pulmonary function, hemoglobin concentration, erythrocyte volume, plasma volume, and total blood volume did not change. Biopsies of the vastus lateralis showed a 28% increase in mean fiber area, no change in fiber type distribution, a 15% increase in capillaries per fiber, and a 38% increase in citrate synthase activity. The data suggest that the small increase in leg cycle VO2max in older men may be due to adaptations in oxidative capacity and increased mass of the strength-trained muscles. PMID- 2312475 TI - Contractile properties of rat soleus muscle after 15 days of hindlimb suspension. AB - The properties of the contractile elements interacting to develop force in atrophied rat soleus muscle were studied by using single skinned fibers, which permitted direct access to the contractile apparatus. Muscle atrophy was induced by 15 days of hindlimb suspension. Suspension resulted in a decrease of maximal tension relative to an important decline in fiber diameter. Ca affinity of the contractile proteins was not changed insofar as the tension-pCa relationship was not shifted along the pCa axis. However, after hindlimb suspension 1) the value of the Hill coefficient from the tension-pCa curve was found to be higher, 2) a higher Ca threshold for activation was reported, and 3) a significant increase in contraction kinetics was described. All these results suggested that after suspension the mechanical properties of the slow-twitch soleus appeared to resemble more closely those of a fast-twitch muscle. Our results were in complete agreement with published histochemical data. PMID- 2312476 TI - Effect of electrical stimulation on intracellular triacylglycerol in isolated skeletal muscle. AB - The contribution of intracellular triacylglycerol (TG) as a substrate for skeletal muscle during electrical stimulation is equivocal. Therefore, the purpose of this study was to investigate the effect of electrical stimulation on the TG content in the isolated intact rat flexor digitorum brevis skeletal muscle preparation by use of two different stimulation protocols. Muscles were electrically stimulated for 1 h either continuously at 1 Hz or intermittently (30 s on, 60 s off) at 5 Hz while incubated in 21 degrees C Krebs bicarbonate buffer (pH 7.4) that contained 11 mM glucose. Control muscles were either frozen immediately after excision or incubated for 1 h. TG content was significantly decreased (P less than 0.05) compared with control concentrations in both stimulated muscle groups, with the greatest reduction (60%) occurring after 5-Hz intermittent stimulation. These data indicate that intramuscular TG is hydrolyzed in response to electrical stimulation in the isolated flexor digitorum brevis muscle preparation. In addition, the type of stimulation (higher frequency intermittent vs. lower frequency continuous) employed influences the amount of intracellular TG hydrolyzed. PMID- 2312477 TI - Respiratory changes in diaphragmatic intramuscular pressure. AB - We attempted to measure diaphragmatic tension by measuring changes in diaphragmatic intramuscular pressure (Pim) in the costal and crural parts of the diaphragm in 10 supine anesthetized dogs with Gaeltec 12 CT minitransducers. During phrenic nerve stimulation or direct stimulation of the costal and crural parts of the diaphragm in an animal with the chest and abdomen open, Pim invariably increased and a linear relationship between Pim and the force exerted on the central tendon was found (r greater than or equal to 0.93). During quiet inspiration Pim in general decreased in the costal part (-3.9 +/- 3.3 cmH2O), whereas it either increased or slightly decreased in the crural part (+3.3 +/- 9.4 cmH2O, P less than 0.05). Similar differences were obtained during loaded and occluded inspiration. After bilateral phrenicotomy Pim invariably decreased during inspiration in both parts (costal -4.3 +/- 6.4 cmH2O, crural -3.1 +/- 0.6 cmH2O). Contrary to the expected changes in tension in the muscle, but in conformity with the pressure applied to the muscle, Pim invariably increased during passive inflation from functional residual capacity to total lung capacity (costal +30 +/- 23 cmH2O, crural +18 +/- 18 cmH2O). Similarly, during passive deflation from functional residual capacity to residual volume, Pim invariably decreased (costal -12 +/- 19 cmH2O, crural -12 +/- 14 cmH2O). In two experiments similar observations were made with saline-filled catheters. We conclude that although Pim increases during contraction as in other muscles, Pim during respiratory maneuvers is primarily determined by the pleural and abdominal pressures applied to the muscle rather than by the tension developed by it. PMID- 2312478 TI - Effect of hindlimb suspension on cardiovascular responses to sympathomimetics and lower body negative pressure. AB - To determine whether hindlimb suspension is associated with the development of cardiovascular deconditioning, male rats were studied before and after undergoing one of three treatment conditions for 9 days: 1) cage control (n = 15, CON), 2) horizontal suspension (n = 15, HOZ), and 3) head-down suspension (n = 18, HDS). Testing included lower body negative pressure administered during chloralose urethan anesthesia and graded doses of sympathomimetic agents (norepinephrine, phenylephrine, and tyramine) administered to conscious unrestrained animals. Both HDS and HOZ were associated with a small decrease in the hypotensive response to lower body negative pressure. The HOZ group, but not the HDS group, exhibited augmented reflex tachycardia. Furthermore, both HDS and HOZ groups manifested reduced pressor responses to phenylephrine after treatment. These reductions were associated with significantly attenuated increases in mesenteric vascular resistance. However, baroreflex control of heart rate was not altered by the treatment conditions. Collectively, these results indicate that 9 days of HDS in rats does not elicit hemodynamic response patterns generally associated with cardiovascular deconditioning induced by hypogravic conditions. PMID- 2312479 TI - Effects of increasing doses of beta-agonists on airway and parenchymal hysteresis. AB - We examined the effects of a deep inhalation on airway caliber before and after increasing doses of a beta-agonist in eight subjects, including one former and two current but mild asthmatics. With bronchodilation the increase in maximal flow on the partial flow-volume curve (P), initiated from functional residual capacity, exceeded that seen on the maximal curve (M), initiated from total lung capacity, such that isovolumic maximal flows diminished after a deep inhalation; i.e., M/P ratios fell with bronchodilation, as we and others have found. Five of eight reversed this downward trend in M/P ratios at higher cumulative doses. Quasistatic pressure-volume curves (QSPV) were simultaneously performed on two of these five and demonstrated a decrease in pressure-volume hysteresis (PVH) at the higher doses associated with a rising M/P ratio. Three of eight had continuing low and diminishing M/P ratio up to the highest dose given. QSPV were performed in two of these three and indicated no change in PVH at any of the doses. One of these two had a repeat study using a subcutaneous beta-agonist after the inhaled drug was given, and the M/P ratio rose as QSPV PVH fell. These data support the relative hysteresis analysis of airway and parenchyma as an explanation for volume history effects on airway caliber. PMID- 2312480 TI - Neutrophils are not necessary for induction of ischemia-reperfusion lung injury. AB - Ischemia-reperfusion lung injury limits lung transplantation. Neutrophil activation and/or xanthine oxidase-mediated purine degradation may cause toxic oxygen metabolite production and lung injury. We investigated whether circulating blood elements are involved in the pathogenesis of ischemia-reperfusion lung injury. Isolated rat lungs were perfused with physiological salt solution (PSS) stabilized with Ficoll until circulating blood elements were not detected in the lung effluent. Lungs were then rendered ischemic by stopping ventilation and perfusion for 45 min at room temperature. Lung injury occurred and was quantitated by the accumulation of 125I-bovine serum albumin into lung parenchyma and alveolar lavage fluid during reperfusion. Lung injury occurred, in the absence of circulating blood elements, when ischemic lungs were reperfused with PSS-Ficoll solution alone. Reperfusion with whole blood or PSS-Ficoll supplemented with human or rat neutrophils did not increase lung injury. Furthermore, during lung ischemia, the presence of neutrophils did not enhance injury. Experiments using PSS-albumin perfusate and quantitating lung injury by permeability-surface area product yielded similar results. Microvascular pressures were not different and could not account for the results. Toxic O2 metabolites were involved in the injury because addition of erythrocytes or catalase to the perfusate attenuated the injury. Thus reperfusion after lung ischemia causes injury that is dependent on a nonneutrophil source of toxic O2 metabolites. PMID- 2312481 TI - Improved frequency response of pneumotachometers by digital compensation. AB - To measure impedance one measures or estimates flow, which is commonly done by measuring the pressure drop across a pneumotachometer. The frequency response characteristics of standard pneumotachometer/pressure transducers (PPT) limit their use to relatively low frequencies. Also, the frequency response of PPTs has been reported to be "load" dependent. Thus, the frequency response characteristics measured under "no-load" conditions, which theoretically could be used to compensate subsequent measurements, may not be appropriate for measurements made under loaded conditions. Another method of measuring impedance exists which depends on a reference impedance element other than a pneumotachometer. In this method, an oscillatory flow signal with known amplitude is generated and used to force the system being tested. Unlike PPTs, this oscillatory flow generator (OFG) is a closed system that allows measurements to be made only during breath holding. Our objective was to determine whether the frequency response of a PPT could be compensated using measurements made under no load conditions, such that it accurately measured an impedance load. The frequency response of the PPT under no-load conditions was measured by the OFG and used to compensate the output of the PPT in subsequent impedance measurements. The compensated PPT was used to measure the impedance of a mechanical structure and the impedances of four human subjects. The impedances of the mechanical structure and the subjects were also measured using the OFG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312482 TI - Ischemia-reperfusion injury in isolated rat hindquarters. AB - The purpose of this study was to determine the suitability of the maximally vasodilated (papaverine) isolated rat hindquarters preparation to study the effects of ischemia and reperfusion on the microvasculature of skeletal muscle. The osmotic reflection coefficient for plasma proteins (sigma) and total vascular resistance (RT, mmHg.ml-1.min.100 g-1) were determined before ischemic periods of 30, 60, 120, 180, and 240 min in intact (with skin) and 30, 60, and 120 min in skinned hindquarters and again after 60 min of reperfusion. In both intact and skinned hindquarters, reductions in sigma and increases in RT were observed during reperfusion and were correlated with the ischemic period duration. After 120 min of ischemia in intact and skinned hindquarters, sigma was reduced from preischemia values of 0.92 +/- 0.02 and 0.89 +/- 0.02 to 0.61 +/- 0.03 and 0.57 +/- 0.03, respectively, whereas RT was increased from preischemia levels of 8.9 +/- 0.3 and 8.1 +/- 0.1 to 28.4 +/- 2.9 and 74.2 +/- 16.8, respectively. The increases in RT were associated with proportional increases in skeletal muscle vascular resistance. Thus, in isolated rat hindquarters, increasing the duration of ischemia results in progressive increases in the permeability to plasma proteins (decreased sigma) and RT, which are associated primarily with skeletal muscle. PMID- 2312483 TI - Spontaneous running increases VO2max and running performance in rats. AB - The effect of spontaneous running activity on maximal O2 consumption (VO2max), running performance, and submaximal O2 consumption (VO2submax, running economy) was studied in rats to determine whether this exercise mode can produce significant training adaptations. Twenty male Long-Evans rats (300 +/- 20 g) were housed in spontaneous activity running wheels, and after 8 wk they were divided into high-, average-, and low-performing groups according to the average spontaneous running distance and tested for maximal running performance, VO2max, and VO2submax. The average-performing rats ran 52% longer than the control rats (P less than 0.01) and 19% longer than the low-performing rats (P less than 0.05). There was no difference in maximum running time to exhaustion between the average- and high-performing rats. The low-performing rats ran 28% longer than the control rats (P less than 0.05). The VO2max of the average-performing rats was 12% greater than in the control rats (P less than 0.01). There were no differences in VO2max between either low-performing and control rats or between average- and high-performing rats. Although the VO2submax was not different between low-, average-, and high-performing rats, in all three groups it was lower than in the control rats (P less than 0.01). Accordingly, we recommend that only those Long-Evans rats that, on average, spontaneously run greater than 11.6 km/wk for a minimum of 8 wk be considered to have undergone a training effect. Rats that perform poorly can be identified as early as 2 wk after the start of training. PMID- 2312484 TI - Effect of sampling on variability and plateau in oxygen uptake. AB - To evaluate the effect of the gas exchange sampling interval on variability and plateau in O2 uptake (VO2), 10 subjects underwent steady-state treadmill exercise at 50% maximal VO2 and 6 subjects underwent maximal testing using a ramp protocol. During steady-state exercise, gas exchange data were acquired by using 10 different sampling intervals. The variability in VO2 was greater as the sampling interval shortened (SD = 4.5 ml.kg-1.min-1 for breath-by-breath vs. 0.8 ml.kg-1.min-1 for 60-s samples). The breath-by-breath data suggested a Gaussian distribution, and most of the variability was attributable to tidal volume (51%). During ramp testing, the slope of the change in VO2 (for each sample) was regressed with time. Considerable variability in the slopes was observed throughout exercise, and in each subject the slopes varied about zero, demonstrating both positive and negative values throughout submaximal effort. These observations were made despite the use of large sampling intervals. Shortening the sample resulted in even greater variability. We conclude that 1) the sampling interval can have a major impact on gas exchange data during exercise and 2) considerable variability exists in the slope of the change in VO2 with a consistent change in external work regardless of the sample used, suggesting that a plateau (defined as the slope of a VO2 sample at peak exercise that does not differ significantly from a slope of zero) in VO2 is not a reliable physiological marker for maximal effort. PMID- 2312485 TI - Stimulation of tracheal ciliary beat frequency by localized tissue incision. AB - Since measurements of basal ciliary beat frequency (CBF) were significantly lower in our intact canine experiments than reports of ciliary activity in rabbits involving surgical intervention, we hypothesized that local tissue trauma stimulates CBF. The effects of minor neck surgery on tracheal CBF in eight barbiturate-anesthetized eucapnically ventilated beagles were investigated. Each dog underwent two studies. Measurements of CBF were made at 1-min intervals on the right lateral midtracheal surface by means of heterodyne mode correlation analysis laser light scattering. In the control study, CBF was measured in each dog for at least 160 min. In the incision study, base-line CBF was measured for at least 40 min. The overlying sternohyoidus muscles were then separated, and a longitudinal 2- to 3-cm incision was made in the trachea caudally from the fourth to the fifth cartilage ring. CBF was measured at least 5 cm distally from the site of tracheal injury for an additional 120 min. Electrocardiogram, rectal temperature, tracheal pressure, exhaled CO2, and arterial blood pressure, PO2, PCO2, and pH remained stable throughout both studies. The mean base-line CBF was 4.7 +/- 0.4 Hz. It increased to 19.5 +/- 2.9 Hz (P less than 0.0001) 100 min after the incision and remained elevated until the end of the study period (P less than 0.0001). The mechanism(s) causing this stimulation may also be responsible for the high "basal" CBF observed in other studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312486 TI - Effect of paraxanthine on FFA mobilization after intravenous caffeine administration in humans. AB - Because it has previously been shown that it takes much more caffeine to cause fat mobilization in vitro than in vivo, it has been suggested that there may be an active metabolite working with caffeine causing an increase in lipolysis in vivo. To determine the relationship between the appearance of paraxanthine (caffeine's major dimethylxanthine metabolite) and free fatty acid (FFA) mobilization after intravenous caffeine administration, 10 men were studied at rest after receiving a dose of 4 mg/kg lean body mass. Venous blood samples were obtained before dosing and at minutes 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180. Serum levels of FFA, glycerol, caffeine, and paraxanthine were determined in duplicate. Concentrations of FFA and glycerol were corrected for plasma volume changes. A high negative correlation was seen between decreases in caffeine and increases in FFA (r = -0.90) and a high positive correlation was seen between the appearance of paraxanthine and FFA (r = 0.93). It was concluded that paraxanthine may play a role in increased lipolysis after caffeine administration in humans. PMID- 2312487 TI - Skeletal muscle adaptation in rats flown on Cosmos 1667. AB - Seven male Wistar rats were subjected to 7 days of weightlessness on the Soviet biosatellite Cosmos 1667. Muscle histomorphometry and biochemical analyses were performed on the soleus (SOL) and extensor digitorum longus (EDL) of flight rats (group F) and compared with data from three groups of terrestrial controls: one subjected to conditions similar to group F in space except for the state of weightlessness (group S) and the others living free in a vivarium (V1, V2). Relative to group V2 (its age and weight-matched control group), group F showed a greater decrease of muscle mass in SOL (23%) than in EDL (11%). In SOL a decrease in the percentage of type I fibers was counterbalanced by a simultaneous increase in type IIa fibers. The cross-sectional area of type I fiber was reduced by 24%. No statistically significant difference in capillarization and enzymatic activities was observed between the groups. In EDL a reduction in type I fiber distribution and 3-hydroxyacyl-CoA-dehydrogenase activity (27%) occurred after the flight. The small histochemical and biochemical changes reported suggest the interest in studying muscular adaptation during a flight of longer duration. PMID- 2312488 TI - Thermoregulatory responses to acute body heating in rats acclimated to continuous heat exposure. AB - Thermoregulatory responses to an acute heat load with intraperitoneal heating (IH) or indirect external warming (EW) by increasing ambient temperature (Ta) were investigated with direct and indirect calorimetry in rats acclimated to environments of 24.0 degrees C (Cn), 29.4 degrees C (H1), and 32.8 degrees C (H2) for greater than 15 days. The rats were placed in a direct calorimeter where the air temperature was maintained at 24 degrees C for the initial 3 h. IH was then made for 30 min through an electric heater implanted chronically (6.5 W.kg-1) in the peritoneal cavity, and EW was performed by raising the jacket water temperature surrounding the calorimeter from 24 to 39 degrees C (0.19 degrees C.min-1). Hypothalamic (Thy) and colonic temperature immediately before the start of the heat load tended to be higher as the acclimation temperature increased. During IH, the threshold Thy for the tail skin vasodilation (Tth) was significantly higher in H2 than in Cn rats. During EW, however, there was no difference in Tth between the groups. Metabolic heat production (M) was slightly suppressed during IH and significantly depressed only in H2 rats. During EW, M was suppressed in all the groups. The magnitude and duration of suppression were greater in H2 rats than in the other two groups. The responses in nonevaporative heat loss and thermal conductance (C) to the rise in Thy did not differ among the three groups during IH. According to the rise in Thy, however, there was a greater C increase in H2 than in Cn and H1 rats during EW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312489 TI - Heat loss responses in rats acclimated to heat loaded intermittently. AB - The present study examined the heat loss response of heat-acclimated rats to direct body heating with an intraperitoneal heater or to indirect warming by elevating the ambient temperature (Ta). The heat acclimation of the rats was attained through exposure to Ta of 33 or 36 degrees C for 5 h daily during 15 consecutive days. Control rats were kept at Ta of 24 degrees C for the same acclimation period. Heat acclimation lowered the body core temperature at Ta of 24 degrees C, and the core temperature level was lowered as acclimation temperature increased. When heat was applied by direct body heating, the threshold hypothalamic temperature (Thy) for the tail skin vasodilation was also lower in heat-acclimated rats than in the control rats. However, the amount of increase in Thy from the resting level to the threshold was the same in all three groups. When heat was applied by indirect warming, threshold Thy was slightly higher in heat-acclimated than in control rats. The amount of increase in Thy from the resting level to the threshold was significantly greater in heat acclimated rats. In addition, Ta and the skin temperature at the onset of skin vasodilation were significantly higher in heat-acclimated rats. The results indicate that heat-acclimated rats were less sensitive to the increase in skin temperature in terms of threshold Thy. The gain constant of nonevaporative heat loss response was assessed by plotting total thermal conductance against Thy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312490 TI - Heat-induced finger vasoconstriction controlled by skin sympathetic nerve activity. AB - Finger blood flow (BF) and skin sympathetic nerve activity (SSA) to the glabrous side of the hand were measured during immersion of the hand in a water bath in which temperature (Tw) was raised every 10 min by steps of 2 degrees C from 35 or 37 to 41 degrees C. The experiments were conducted during the summer in rooms in which ambient temperature was 28-32 degrees C or 35 degrees C. The nine healthy male subjects were wearing summer clothes. Finger BF through vessels located deep in the skin was measured by using laser-Doppler flowmetry (ALF-2100, Advance). With the use of a tungsten microelectrode SSA was recorded directly from the median nerve at the wrist or antecubital fossa of the tested arm. With finger vessels already dilated at Tw of 35 or 37 degrees C, finger BF decreased, with a concomitant increase in the SSA bursts as Tw rose to 39-41 degrees C. We confirmed in one subject that anesthetic blockade of the median nerve at the site proximal, but not distal, to the recording site blocked responses to the step rise in Tw in the SSA bursts and in finger BF. From these results we conclude that, with the subject in a warm state, blood vessels of the finger respond to local heating with vasoconstriction, and this finger vasoconstriction is evoked reflexively, largely through the increased sympathetic outflow to the resistance vessels of the finger. PMID- 2312491 TI - Diffusivity dependence of multiple-breath washouts of lung periphery. AB - Subpleural concentrations of He and SF6 were measured during multiple-breath washouts from isolated dog lungs. Tidal volume, inspiratory flow, and frequency were in the normal range of canine ventilation. For each gas, there was a local minimum in concentration during inspiration (Cinsp) and a local maximum in concentration during exhalation (Cexp). SF6 exhibited a deeper inspiratory trough than He for each breath of every washout. For large tidal volumes (10-20 ml/kg), Cexp approximated a single exponential decay and He was cleared more rapidly than SF6. For small tidal volumes (2.5 ml/kg), Cexp was multiexponential and SF6 was cleared more rapidly than He. Cinsp/Cexp (a measure of the depth of the inspiratory trough) and the kinetics of Cexp decay were determined for washouts using a tidal volume of 10 and 20 ml/kg and different inspiratory flows. Under all conditions, an increase of inspiratory flow resulted in a deeper inspiratory trough for both He and SF6. For washouts using 10 ml/kg and 60 breaths/min, an increase of inspiratory flow increased the clearance of both gases. In washouts using lower ventilatory frequencies, gas clearance was independent of inspiratory flow. These findings are contrary to predictions of contemporary models of convection and diffusion in the lung. This study suggests that convective axial mixing and radial diffusion in the airways are important determinants of pulmonary gas transport. PMID- 2312492 TI - Platelets in health and disease. PMID- 2312493 TI - Enhanced anchorage independent colony formation at increased agar concentrations in malignant mouse epithelial cell lines. PMID- 2312494 TI - Effects of medium and substratum conditions on the rates of DNA synthesis in primary cultures of bile ductular epithelial cells. AB - Select medium and substratum conditions were investigated for their effects on semiconservative DNA synthesis in essentially pure primary cultures of bile ductular epithelial cells that were initially isolated from cholestatic rat livers at 6 to 10 wk after bile duct ligation. DNA synthesis in these cultured cells was serum-dependent, being at its highest level when the concentration of fetal bovine serum present in the medium was maintained at 10%. This serum dependent DNA synthesis was completely inhibited when 10 mM hydroxyurea was also included in the medium, and bile ductular cells cultured in the continued presence of 1.0% fetal bovine serum showed only marginal DNA synthesis during 8 to 10 d of primary culture when compared with no-serum controls. Maximum rates of serum-dependent DNA synthesis were obtained when the bile ductular cells were cultured for 7 to 14 d on tissue culture plastic coated with either fibronectin from bovine plasma or type I rat-tail collagen. Cells cultured on plastic coated with basement membrane Matrigel exhibited the lowest levels of DNA synthesis, whereas those on plastic alone had intermediate amounts. Furthermore, the addition of epidermal growth factor (50 ng.ml-1.d-1) to medium supplemented with 1.0% fetal bovine serum greatly enhanced the rate of DNA synthesis in bile ductular cells after 6 d in primary culture on type I collagen-coated plastic over that measured in solvent control cultures. These findings indicate that our bile ductular epithelial cell culture model is potentially useful in the study of biliary cell growth regulation and carcinogenesis. PMID- 2312495 TI - Effects of ethanol on rat Schwann cell proliferation and myelination in culture. AB - It is possible to treat dissociated embryonic rat dorsal root ganglia in culture to inhibit proliferation of all nonneuronal cells except Schwann cells. Neurons have been shown to produce a mitogenic stimulus for Schwann cells under these conditions. Additionally, myelin-competent neurons induce Schwann cells to elaborate myelin sheaths. Groups of sibling cultures were exposed to various nonlethal concentrations of ethanol (0, 43, 86, or 172 mM) for 4 wk. Cultures were assessed weekly by light microscopy in a blind fashion for evidence of Schwann cell proliferation and myelin formation. Ethanol adversely affected both Schwann cell proliferation and myelin formation in culture. No obvious differences in neuronal morphology were observed among the various groups of cultures by light or electron microscopy. These observations suggest that ethanol might interfere with Schwann cell proliferation and myelin formation in culture by one or both of the following means: a) inhibit neuronal production of signals for Schwann cell proliferation and myelination or b) impede Schwann cell responses to neuronal signals. Investigation of these possibilities in culture may provide insight into neuropathologic mechanisms operative in the fetal alcohol syndrome or alcohol-associated peripheral neuropathy in humans. PMID- 2312497 TI - Cryopreservation of cynomolgus monkey (Macaca fascicularis) hepatocytes for subsequent culture and protein synthesis studies. AB - A method is described for the preservation and subsequent recovery of hepatocytes obtained by collagenase perfusion of cynomolgus monkey (Macaca fascicularis) livers. The fresh cells are suspended in fetal bovine serum containing 10% dimethylsulfoxide and, using a microprocessor-controlled, liquid nitrogen freezing chamber and a specific cooling protocol, processed in such a way that they can be stored in liquid nitrogen for several months and still restored to active culture. When the cryopreserved cells were established in culture, they were found to actively synthesize and secrete both albumin and apolipoprotein A I. That, taken together with morphologic evidence, was viewed as indication that the cells recovered in culture were in fact hepatocytes and not some other cell type from the monkey liver. The availability of this procedure for storing hepatocytes should contribute significantly to the efficient use of nonhuman primates as models with which to study hepatic metabolism. PMID- 2312496 TI - Interactions of cultured rat synovial and ocular ciliary body cells with two strains of Mycoplasma arthritidis. AB - Strains of Mycoplasma arthritidis differ in their ability to cause joint and ocular inflammations. Although the reasons for this difference are not fully understood, pathogenic mycoplasmas commonly require close associations with the cells they damage. Using 3H-uridine labeled mycoplasma, we compared cellular interactions of in vitro cultivated rat synovial and ocular ciliary body epithelial cells with two American Type Culture Collection strains of M. arthriditis shown to differ in their virulence. Radiolabeling assays gave evidence of a stronger retention capability on cultured cells by the more pathogenic strain, 14152. Scanning electron microscopy demonstrated cellular associations with the two strains of mycoplasma, with more of the 14152 adhering to both cell types. Examination by transmission electron microscopy showed evidence of contact between the more virulent 14152 strain and both cell types, but no similar evidence with the comparatively less virulent strain, 19611. The pathogenicity of different strains of M. arthritidis may vary according to their ability to closely associate with specific target cells involved in the disease process. PMID- 2312498 TI - Changes in proteoglycans of cultured pig aortic smooth muscle cells during subculture. AB - Smooth muscle cells were cultured from pig aorta. Changes in both the growth and the properties of sulfated proteoglycans were observed during passage. The population doubling time during log phase growth was 34 h from Passages 3 to 7-8 but 20 h at the Passage 11, and the cell density at the stationary phase, was 86,000 and 136,000 cells/cm2 at Passages 3 and 11, respectively. Structural characteristics of sulfated proteoglycans secreted into the medium were investigated after metabolic labeling with [35S]-sulfate. Significant differences were observed with age in vitro: a) [35S]proteoglycan complexes were in a greater amount at Passage 10 than at Passage 3; b) the hydrodynamic size of at least 45% of subunits and about 90% of monomers decreased with in vitro aging; c) this decrease in the size of proteoglycans was partly due to a decrease in the size of their glycanic chains; d) an increase of 15% in the proportion of dermatan sulfate was observed when cells were subjected to 10 passages. PMID- 2312499 TI - Effects of attachment substrates on the growth and differentiation of LLC-PK1 cells. AB - The growth and differentiation of an established renal epithelial cell line, LLC PK1, on membrane bound mussel adhesive protein (MAP), collagen, and extracellular matrix (ECM) in serum-containing medium was studied. Cell attachment and growth on uncoated- vs. protein-coated cellulose nitrate and acetate membranes did not differ significantly, and confluence was achieved on all membranes. However, cells remained in a single monolayer only when plated on collagen or ECM. LLC-PK1 monolayers grown on ECM-coated membranes displayed the highest transepithelial D glucose transport (333 +/- 22 ng.cm-2.min-1) whereas cells plated on collagen coated membranes displayed the lowest (94 +/- 23 ng.cm-2.min-1). Glucose flux values increased with age of the culture, reaching a plateau at 28 d postseeding. These results indicate that the underlying substratum and cell age can affect differentiation of renal epithelial cells in vitro. PMID- 2312501 TI - Temperature sensitivity on proliferation and morphologic alteration of human esophageal carcinoma cells in culture. AB - As basic studies of hyperthermia and hypothermia on malignant tumor, the kinetics of proliferative activity, the morphologic changes in the two cell lines, SGF-3 and SGF-5, established in our department after the change of culture temperature were examined. The results obtained were: a) A significant difference was found in the sensitivity to temperatures between the two cell lines originated from human esophageal squamous cell carcinoma. The temperature range allowing cultured cell to proliferate were from 31 degrees to 39 degrees C in SGF-3 and from 29 degrees to 41 degrees C in SGF-5. b) Minor difference occurred in the results between the two cell lines examined during the recovery of proliferative activity, but no proliferative activity was discovered after the cells were exposed to 42 degrees C for 72 h. Two cell lines resumed their proliferation after having been exposed to 27 degrees or 28 degrees C for 72 h. c) Morphologic changes of the cell lines cultured at high temperature were cytoplasmic vacuolation and cell aggregation by phase contrast microscope and the increase of heterochromatin, the decrease of granular formation in nucleoli, and nucleolar vacuolation by transmission electron microscopy (TEM). At low temperatures the changes observed included cytoplasmic ballooning and circumnuclear halo formation by phase contrast microscope, and the increase of heterochromatin, nucleolar segregation, swelling of mitochondria, and dilatation of rough endoplasmic reticulum (rER) by TEM. PMID- 2312500 TI - Morphologic plasticity and periodicity: porcine cerebral microvascular cells in culture. AB - Porcine cerebral microvascular (PCMV) endothelial cell cultures and pericyte endothelial cell cocultures were established and the self-organizational properties of the cells were examined in various culture conditions. Cultured PCMV endothelial cells were characterized by the capacity to produce prostacyclin in response to bradykinin. Cultured PCMV pericytes were identified with a smooth muscle actin-specific stain. PCMV endothelial cells organized into cord structures when left in culture for several weeks without passage. Lumina were observed in cross sections of these cords and appeared to form through a process of cell-selective autolysis. PCMV endothelial cells required three dimensions for self-organization, forming suspended cords in planes that either intersected or paralleled the culture vessel floor. After formation, suspended cords continued to exhibit a morphologic plasticity punctuated by the coordinated migrations of PCMV endothelial cells en masse. Sequential propagation of PCMV endothelial cell monolayers and development of suspended capillarylike cords recurred cyclically when cells were left in culture without passage for several weeks. Cord development was also observed in PCMV pericyte-endothelial cell cocultures with large proportions of pericytes. However, pericytes were not located in cross sections of suspended cords formed in coculture. Apparently, in some conditions of PCMV coculture, populations of PCMV endothelial cells and pericytes segregate. Retina-derived growth factor (RDGF) promoted this cell-type segregation and the subsequent formation of suspended cords in PCMV cocultures, although its exact mode of action is unclear. These results indicate that cultured cerebral microvascular endothelial cells and pericytes have capacities for complex, temporal self-organization that varies according to culture conditions. PMID- 2312502 TI - Action of ornithine alpha ketoglutarate on DNA synthesis by human fibroblasts. AB - Ornithine alpha ketoglutarate (OKG) is largely used in clinical nutrition for its anabolic effects. However, the mechanism of its action remains questionable. We investigated the effect of OKG on the rate of DNA synthesis in human fibroblasts. The in vitro experimental procedure required to demonstrate in cell culture the anabolic effects of OKG observed in vivo was found to be glutamine-free and serum poor medium with sparse cells. In these conditions, OKG induced a significant increase in [3H]thymidine incorporation compared to untreated control cells. This effect was dose-dependent and was observed in all the cultures tested. Taken individually, the two constituents of OKG, i.e. alpha KG and Orn, also showed a stimulatory effect, but did not demonstrate a dose-dependent response. Concomitant analysis of extracellular aminoacids showed in alpha KG-treated cultures an increase in glutamate and a decrease in aspartate, suggesting a cellular transamination of alpha KG. Glutamine, which is the preferential energetic substrate of fibroblasts, can be produced from glutamate and might play a role in the action of OKG. Moreover, OKG induced a rise in the cellular polyamine content. This, in association with the inhibitory effect on OKG action of difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, suggests a link between the polyamine biosynthesis pathway and the anabolic effect of OKG. PMID- 2312503 TI - Serum-free medium conditions for steroidogenesis of bovine follicular thecal cells cultured on collagen gel matrix. AB - Thecal cells isolated from bovine ovarian follicles were cultured with a serum free basal medium or a serum-free complete medium in the presence or absence of collagen gel matrix, and their cellular proliferation and steroidogenesis were compared with those of cells cultured with a serum-containing medium. The cells cultured with the serum-free basal medium produced larger amounts of progesterone, androstenedione, and estradiol than the cells cultured with the serum-containing medium, but no appreciable cell proliferation was observed in the serum-free medium. Response of thecal cells to 8 bromo-cAMP, a steroidogenic agent, varied according to the type of steroid production examined and the type of culture medium used. In a cultivation period of 4 d, progesterone production was stimulated about five-fold by 8 bromo-cAMP in the serum-free complete medium on collagen gel matrix and in the serum-free basal medium without collagen matrix, whereas androstenedione production was stimulated about three- to fourfold in the serum-free complete medium on collagen gel matrix and in the serum-free basal medium with or without collagen matrix. Estradiol production, however, was significantly suppressed by 8 bromo-cAMP in the serum-free complete medium on collagen gel matrix and also in the serum-containing medium. Thus, among the conditions examined, the most suitable primary culture media for steroidogenesis of thecal cells were the serum-free media, especially serum-free complete medium on collagen gel matrix. PMID- 2312506 TI - Scientific progress vs environmental safety--a morality play for the next century. PMID- 2312504 TI - Myogenesis and histogenesis of skeletal muscle on flexible membranes in vitro. AB - Primary muscle cell cultures consisting of single myocytes and fibroblasts are grown on flexible, optically clear biomembranes. Muscle cell growth, fusion and terminal differentiation are normal. A most effective membrane for these cultures is commercially available Saran Wrap. Muscle cultures on Saran will, once differentiated, contract vigorously and will deform the Saran which is pinned to a Sylgard base. At first, the muscle forms a two-dimensional network which ultimately detaches from the Saran membrane allowing an undergrowth of fibroblasts so that these connective tissue cells completely surround groups of muscle fibers. A three-dimensional network is thus formed, held in place through durable adhesions to stainless steel pins. This three-dimensional, highly contractile network is seen to consist of all three connective tissue compartments seen in vivo, the endomysium, perimysium and epimysium. Finally, this muscle shows advanced levels of maturation in that neonatal and adult isoforms of myosin heavy chain are detected together with high levels of myosin fast light chain 3. PMID- 2312507 TI - A mycotoxin miscellany. PMID- 2312505 TI - Opposite effects of monokines (interleukin-1 and tumor necrosis factor) on proliferation and heparin-binding (fibroblast) growth factor binding to human aortic endothelial and smooth muscle cells. AB - Heparin-binding (fibroblast) growth factors (HBGF) are mitogens for both human aortic endothelial and smooth muscle cells. Under similar conditions, both vascular cells display similar numbers of specific HBGF binding sites with similar apparent affinity for HBGF. The monokines, interleukin-1 and tumor necrosis factor, inhibit endothelial cell growth and stimulate smooth muscle cell growth. The opposite mitogenic effects correlate with reduction and increase in HBGF receptor number displayed by endothelial and smooth muscle cells, respectively. These results suggest that the two monokines may depress endothelial cell regeneration and augment smooth muscle cell hyperplasia by differential modulation of the HBGF receptor in the two vascular cell types. PMID- 2312508 TI - Methodology for the analysis of benzimidazole anthelmintics as drug residues in animal tissues. AB - Methodology for the analysis of 8 benzimidazoles as residues in bovine liver is reported. Spiked tissues were extracted by homogenization in saline and ammonium hydroxide and blending with diatomaceous earth. This matrix was packed into a column, and the benzimidazoles were eluted with ethyl acetate. After the sample was further purified, benzimidazoles were separated and quantitated by liquid chromatography with ultraviolet detection (290 nm). Liver tissue samples obtained from cattle which had undergone a drug depletion study of fenbendazole administered per os were analyzed using these methods. The results of these analyses and the application of this approach to multiresidue analysis of drugs in animal tissues are discussed. PMID- 2312509 TI - Liquid chromatographic determination of desfuroylceftiofur metabolite of ceftiofur as residue in cattle plasma. AB - A liquid chromatographic (LC) method has been developed for the determination of the desfuroylceftiofur metabolite of ceftiofur as a residue in the plasma of animals. Plasma sample in 0.1M pH 8.7 phosphate buffer containing dithioerythritol is incubated under nitrogen for 15 min at 50 degrees C. The sample is centrifuged, charged to a C18 cartridge, and washed with 0.1M ammonium acetate. The desfuroylceftiofur residue on the cartridge is derivatized by adding 0.1M ammonium acetate containing iodoacetamide and letting the cartridge stand in the dark for 30 min. The cartridge is then drained and rinsed, and the desfuroylceftiofur acetamide is eluted with methanol. The mixture is evaporated to dryness, dissolved in pH 10.6 sodium hydroxide, and charged to a SAX cartridge. The derivative is eluted with 2% acetic acid, reduced in volume, and dissolved in mobile phase for liquid chromatography. The LC system includes a C8 column and guard cartridge with UV detection at 254 nm. The gradient mobile phase (flow rate 1 mL/min) is 0.01M pH 5 ammonium acetate programmed to 29% methanol water (60 + 40) in 25 min. Recoveries were 90-100% with a sensitivity of 0.1 ppm or less. The procedure has been applied to the plasma of cattle, rats, horses, pigs, and dogs. PMID- 2312510 TI - Equivalency of protein determination in feed on Bran & Luebbe Traacs 800 autoanalyzer with AOAC semiautomated method: minicollaborative study. AB - A new generation of autoanalyzers was collaboratively studied for equivalency with instrumentation described in the AOAC method for crude protein in animal feeds. Twenty predigested samples were analyzed by 4 collaborators using standards that were provided. Means were comparable; the overall average difference was 0.07% protein. Analysis of variance indicated no evidence for an instrument difference. The method describing use of the Traacs 800 autoanalyzer as an alternative system has been adopted official first action. PMID- 2312511 TI - Determination of total sulfite in shrimp, potatoes, dried pineapple, and white wine by flow injection analysis: collaborative study. AB - A method for the determination of total sulfite in shrimp, potatoes, dried pineapple, and white wine by flow injection analysis (FIA) was collaboratively studied by 8 laboratories. In the method, the sample solution is reacted with sodium hydroxide to liberate aldehyde-bound sulfite. The sample stream is acidified to produce SO2 gas, which diffuses across a Teflon membrane in the gas diffusion cell into a flowing stream of malachite green. The degree of discoloration of the malachite green is proportional to the amount of sulfite in the sample solution. Red wine was included in the study but interlaboratory precision for these samples was not satisfactory and correlation with Monier Williams results was poor. The present method is not recommended for use with these samples. For shrimp, potatoes, dried pineapple, and white wine, average reproducibility (RSDR) of results was 25% for samples at 10 ppm SO2 and 10% for samples at greater than 50 ppm. Overall average reproducibility was 14%. Recoveries of sulfite added to samples averaged 80%. Comparison of FIA with the Monier-Williams method indicated comparable results by the 2 methods. The FIA method has been adopted official first action for determination of greater than or equal to 5 ppm total sulfite in shrimp, potatoes, dried pineapple, and white wine. PMID- 2312512 TI - Detection and semiquantitative estimation of chlorinated organic pesticide residues in foods by paper chromatography. 1959. PMID- 2312513 TI - Liquid chromatographic determination of polydextrose in food matrixes. AB - A liquid chromatographic (LC) method has been developed to determine the content of polydextrose, a water-soluble 1 calorie/g bulking agent, in food matrixes such as cookies, cakes, fruit spreads, and chocolate toppings. This analysis, which requires use of a blank matrix, provides a feasible means to control the manufacture of foods containing this additive and provides a component for the accurate determination of the caloric value of a particular food product. The method involves aqueous extraction of the polydextrose from the food matrix followed by separation on a carbohydrate analysis column. The LC system uses a mobile phase of 0.005M CaSO4.2H2O and a refractive index detector for quantitation. Polydextrose recoveries from the food matrixes varied from 91.5 to 100.9% with assay precision, expressed as coefficient of variation, ranging from 0.7 to 4.3%. Each error estimate was derived from 5 parallel determinations. The present methodology is precise and selective in contrast to the modified classical phenol-sulfuric acid colorimetric method for assaying carbohydrates, which had been used for polydextrose determination in food matrixes in the past. Because the coefficient of variation frequently exceeded 10%, replicate analyses were necessary to achieve quantitation. PMID- 2312515 TI - Outlier detection in collaborative studies. AB - Extended tables of critical values for the reduction in standard deviation tests for single and paired outliers recommended for collaborative studies are presented. Critical values for the single outlier test are derived mathematically and those for the paired test are derived from computer simulations. The single outlier test becomes more and more stringent as the size of the study increases. A confidence interval approach is suggested as a means to treat all sizes of collaborative studies in a uniform manner. PMID- 2312514 TI - Colorimetric determination of hydroxyproline as measure of collagen content in meat and meat products: NMKL collaborative study. AB - A colorimetric method for the determination of hydroxyproline as a measure of collagen in meat and meat products has been collaboratively studied in 18 laboratories. The method includes hydrolysis with sulfuric acid, oxidation with chloramine-T, and formation of a reddish purple complex with 4 dimethylaminobenzaldehyde. Five frozen and 3 freeze-dried samples were tested, ranging in content from 0.11 to 0.88% and from 0.39 to 4.0% hydroxyproline, respectively. The mean values of 2 identical samples were 0.245 and 0.251%. The average recovery from a spiked sample was 96.1%. The hydroxyproline content of a known sample (a mixture of 2 samples in the ratio 5:2) was calculated to 1.42%, which agrees well with the analytical result, 1.40%. In comparison with other collaborative studies, based on the ISO analytical method, the repeatability and reproducibility of this method agree well with the other results. This method was accepted as an official NMKL method by all national Committees, and has been adopted official first action by AOAC as an NMKL-AOAC method. PMID- 2312516 TI - Comparison of three liquid chromatographic methods with FDA optimized Monier Williams method for determination of total sulfite in foods. AB - Three liquid chromatographic (LC) methods employing amperometric detection were compared with the collaboratively studied FDA optimized Monier-Williams distillation method for the determination of total sulfite in 5 food types. The foods included lemon juice, white wine, instant mashed potatoes, golden raisins, and onion flakes. Two of the LC methods (one employing headspace sampling and the other direct injection) used ion-exchange chromatography with a basic mobile phase (pH about 10.8) and a glassy carbon electrode; the third (employing direct injection) used ion-exclusion chromatography with an acidic mobile phase (pH about 2) and a platinum electrode. All 4 methods produced similar results for the wine, lemon juice, and raisins. Results were different for instant mashed potatoes and onion flakes. The headspace-LC method and direct ion-exclusion LC method, both of which employed an alkaline sample extraction, yielded significantly higher values for sulfite in instant potatoes than did the other 2 methods. A large interfering peak with both direct LC methods prevented quantitation of sulfite in the onion flakes. All methods can detect sulfite as low as about 1 microgram/g in 4 of 5 food types examined. PMID- 2312517 TI - Isokinetic plantar flexion: experimental results and model calculations. AB - In isokinetic experiments on human subjects, conducted to determine moments that can be exerted about a joint at different angular velocities, joint rotation starts as soon as the moment increases above the resting level. This contraction history differs from the one in experiments on isolated muscle, where the force is allowed to increase to an isometric level before shortening is initiated. The purpose of the present study was to determine the influence of contraction history on plantar flexing moments found during maximal voluntary plantar flexion on an isokinetic dynamometer. In ten subjects, plantar flexing moments were measured as a function of ankle angle at different angular velocities. They were also calculated using a model of the muscle-tendon complex of the human triceps surae. The model incorporates elastic tendinous tissue in series with muscle fibers. The input of the model consists of time histories of active state (the force generating capacity of contractile elements) and shortening velocity of the muscle-tendon complex. Different time courses of active state were offered at fixed length of the muscle-tendon complex. The time course yielding a close match between the calculated rise of plantar flexing moment and the rise measured during fixed angle contractions was used to calculate moment-angle curves for isokinetic plantar flexion. The active state value reached when a peak occurred in calculated moment-angle curves was found to be lower if the angular velocity was made higher. Comparing measured and calculated results, it was concluded that moment-angular velocity diagrams determined in studies of isokinetic plantar flexion in human subjects reflect not only the influence of shortening velocity of contractile elements on the force which can be produced by plantar flexors. PMID- 2312518 TI - Series elasticity in frog sartorius muscle subjected to stretch-shortening cycles. AB - Changes in stiffness during stretch-shortening cycles were studied by applying prestretches of different rates and amplitudes on the tetanized sartorius muscle of the frog and measuring series elastic component characteristics during a subsequent quick release. Series elastic component stiffness was found to be dependent on the mechanical parameters of the stretching phase, and the so-called 'Cavagna effect' (increase in compliance) was rarely observed. The results are discussed in terms of improvement in muscle efficiency. Thus, an increase in stiffness during force generation will favour a better transmission of force and will reduce the coupling time whereas the opposite evolution during SEC recoil will allow a better release of potential energy. PMID- 2312519 TI - A finite deformation theory for cartilage and other soft hydrated connective tissues--I. Equilibrium results. AB - The determination of valid stress-strain relations for articular cartilage under finite deformation conditions is a prerequisite for constructing models for synovial joint lubrication. Under physiological conditions of high strain rates and/or high stresses in the joint, large strains occur in cartilage. A finite deformation theory valid for describing cartilage, as well as other soft hydrated connective tissues under large loads, has been developed. This theory is based on the choice of a specific Helmholtz energy function which satisfies the generalized Coleman-Noll (GCN0) condition and the Baker-Ericksen (B-E) inequalities established in finite elasticity theory. In addition, the finite deformation biphasic theory includes the effects of strain-dependent porosity and permeability. These nonlinear effects are essential for properly describing the biomechanical behavior of articular cartilage, even when strain rates are low and strains are infinitesimal. The finite deformation theory describes the large strain behavior of cartilage observed in one-dimensional confined compression experiments at equilibrium, and it reduces to the linear biphasic theory under infinitesimal strain and slow strain rate conditions. Using this theory, we have determined the material coefficients of both human and bovine articular cartilages under large strain conditions at equilibrium. The theory compares very well with experimental results. PMID- 2312520 TI - A musculoskeletal model of the human lower extremity: the effect of muscle, tendon, and moment arm on the moment-angle relationship of musculotendon actuators at the hip, knee, and ankle. AB - We have developed a musculoskeletal model of the human lower extremity for computer simulation studies of musculotendon function and muscle coordination during movement. This model incorporates the salient features of muscle and tendon, specifies the musculoskeletal geometry and musculotendon parameters of 18 musculotendon actuators, and defines the active isometric moment of these actuators about the hip, knee, and ankle joints in the sagittal plane. We found that tendon slack length, optimal muscle-fiber length, and moment arm are different for each actuator, thus each actuator develops peak isometric moment at a different joint angle. The joint angle where an actuator produces peak moment does not necessarily coincide with the joint angle where: (1) muscle force peaks, (2) moment arm peaks, or (3) the in vivo moment developed by maximum voluntary contractions peaks. We conclude that when tendon is neglected in analyses of musculotendon force or moment about joints, erroneous predictions of human musculotendon function may be stated, not only in static situations as studied here, but during movement as well. PMID- 2312522 TI - The geometry of the aortic root in health, at valve disease and after valve replacement. AB - For the design of aortic valve prostheses with a separation-free flow field and minimum pressure drop the geometry of the aortic root is of high importance, since an appropriate adjustment of the prostheses to the surrounding geometry could largely reduce the risk of thromboembolic complications. For the investigation of the geometry of the aortic root 604 angiographic films out of a total stock of 15,000 of the Medical Clinic I were evaluated. The film material was preclassified into five clinical categories according to the patient's data. For each category characteristic geometries could be derived in non-dimensional form. PMID- 2312521 TI - A theoretical model for stress-generated fluid flow in the canaliculi-lacunae network in bone tissue. AB - A mathematical model was developed to study stress-induced fluid flow in the canaliculi-lacunae system in an osteon. The effect of canaliculi diameters on the magnitude and depth of penetration of squeeze flow through the canaliculi system was investigated. An optimal canaliculus diameter (which would maximize the fluid velocity through the canaliculi) was determined. For canaliculi diameters of 0.2 micron, squeeze flow can nourish four to five concentric layers of osteocytes in an osteon. It is possible that such stress-induced flow may be important in bone remodeling, and that lack of such flow may be one cause for producing osteoporosis due to immobilization. PMID- 2312523 TI - Muscarinic receptor subtypes mediating negative chrono- and inotropic responses in isolated, blood-perfused dog right atria. AB - 1. Negative chrono- and inotropic responses to both carbachol (CCh) into the sinus node artery and electrical stimulation of vagal nerve fibres (ES) were studied in the isolated, blood-perfused canine right atrium, using four muscarinic receptor antagonists, atropine, 4-DAMP, AF-DX 116 and pirenzepine. 2. ES and CCh evoked negative chrono- and inotropic responses in a frequency dependent manner and in a dose-related manner, respectively. 3. Each antagonist inhibited these negative chrono- and inotropic responses in a dose-dependent manner. The ranking order of blocking potency (ID50) was atropine greater than or equal to 4-DAMP greater than AF-DX 116 greater than pirenzepine. 4. The ID50 of atropine, 4-DAMP or AF-DX 116 against sinus rate decreases induced by CCh or ES was not significantly different from that against the atrial tension decreases. In contrast, the ID50 of pirenzepine against sinus rate decreases evoked by CCh (17 nmol) or ES (20 nmol) was significantly smaller than that for the atrial tension decrease (CCh, 200 and ES, 53 nmol, respectively). 5. These results suggest that, in the isolated dog atrium, M2-receptor-mediated-responses are predominant. However, M1-receptor activation may also be involved in sinus rate response. PMID- 2312524 TI - Age-related differences in the depressor responses to sodium nitroprusside and nifedipine in anaesthetized rats. AB - 1. The blood pressure lowering actions of sodium nitroprusside (SNP) and nifedipine were compared in 5-month and 22-month pentobarbitone-anaesthetized Sprague-Dawley rats. 2. Five-month-old rats had significantly higher resting diastolic blood pressure (DBP) than 22-month rats and this may explain why SNP (1 30 micrograms kg-1) produced significantly greater falls of DBP in absolute terms in 5-month animals. 3. The depressor responses to nifedipine were similar in young and old rats, despite differences in resting DBP, suggesting that, in comparison to nifedipine, SNP is less effective at lowering DBP in aged rats. PMID- 2312525 TI - The effect of inhibitors of prostaglandin formation on contraction of the rat, rabbit and human vas deferens. AB - 1. The rat vas deferens releases both PGE2 and PGF2 alpha under basal conditions in vitro but the human vas deferens synthesizes prostaglandins only when arachidonic acid is supplied exogenously. 2. The release of PGE2 and PGF2 alpha is augmented by alpha-adrenoceptor activation or by BaCl2, both of which cause contraction. 3. Release of PGE2 and PGF2 alpha is substantially inhibited by indomethacin 10 micrograms ml-1 which does not affect contraction. 4. Contraction is strongly inhibited by higher concentrations of indomethacin (50-80 micrograms ml-1). 5. It is concluded that the release of PGE2 and PGF2 alpha from the rat and human vas deferens is not correlated with contraction. PMID- 2312526 TI - Radiographic measurements and clinical decisions. PMID- 2312527 TI - Measurement of the Cobb angle on radiographs of patients who have scoliosis. Evaluation of intrinsic error. AB - To quantitate the intrinsic error in measurement, fifty anteroposterior radiographs of patients who had scoliosis were each measured on six separate occasions by four orthopaedic surgeons using the Cobb method. For the first two measurements (Set I), each observer selected the end-vertebrae of the curve; for the next two measurements (Set II), the end-vertebrae were pre-selected and constant. The last two measurements (Set III) were obtained in the same manner as Set II, except that each examiner used the same protractor rather than the one that he carried with him. The pooled results of all four observers suggested that the 95 per cent confidence limit for intraobserver variability was 4.9 degrees for Set I, 3.8 degrees for Set II, and 2.8 degrees for Set III. The interobserver variability was 7.2 degrees for Set I and 6.3 degrees for Sets II and III. The mean angles differed significantly between observers, but the difference was smaller when the observers used the same protractor. PMID- 2312528 TI - Measurement of scoliosis and kyphosis radiographs. Intraobserver and interobserver variation. AB - Interobserver variations for measurements of the Cobb angle on radiographs of patients who had kyphosis were comparable with those on the radiographs of patients who had scoliosis. Four staff orthopaedists and one physical therapist measured eight radiographs that showed scoliosis and twenty that showed kyphosis. The measurements were made on two occasions and in random order. For scoliosis, the average difference between readings was 3.8 degrees, and 95 per cent of the differences were 8 degrees or less (range, 0 to 10 degrees). These findings were in keeping with those of other published reports. For kyphosis, the average difference between readings was 3.3 degrees, and 95 per cent of the differences were 7 degrees or less (range, 0 to 30 degrees). One investigator rated the kyphosis radiographs with respect to clarity. There was a trend to less variation with clearer radiographs, but this was not significant. The end-vertebrae were pre-selected for some radiographs and were freely chosen by the interpreter for others. Reliability was not significantly improved when the end-vertebrae of the curve had been pre-selected. Using the statistical method called tolerance limits, we determined that if one were to be 95 per cent confident that a measured difference represented a true change, the difference would have to be 10 degrees for scoliosis radiographs and 11 degrees for kyphosis radiographs. The probability that a measured difference is due to measurement error alone (that is, a false-positive reading) was calculated. PMID- 2312529 TI - Results of revision of hip arthroplasty with cement. A five to fourteen-year follow-up study. AB - We reviewed the results of sixty revisions of cemented total hip replacement in fifty-four patients who had complete clinical and radiographic follow-up. All of the revisions were performed by a standardized operative technique, in which both components of a single model of prosthesis were fixed with cement. In nineteen of the sixty revisions, autogenous grafts from the iliac crest were used for a deficiency in the roof of the acetabulum. After five to fourteen years, there had been two infections and four additional revisions for aseptic failure. Three cups had migrated, and another seven were surrounded by a complete radiolucent line. Five femoral components had subsided, and another eleven were surrounded by a complete radiolucent line. Survivorship analysis of eighty revisions showed a cumulative survival of about 85 per cent at fourteen years. In these relatively old patients, the outcome of revision of hip replacement with the described operative technique was very satisfactory. PMID- 2312530 TI - Total elbow arthroplasty with a non-constrained surface-replacement prosthesis in patients who have rheumatoid arthritis. A long-term follow-up study. AB - Thirty-seven elbows in thirty-six patients who had rheumatoid arthritis had a total elbow arthroplasty with insertion of a non-constrained surface-replacement prosthesis. The patients were followed for an average of nine years and six months, the longest follow-up being seventeen years. A good result was seen in twenty-nine elbows; a fair result, in one; and a poor result, in seven. The reasons for the poor results were gross posterior displacement of the humeral component in five elbows, persistent subluxation with pain in one, and recurrent ankylosis in one. Of the five elbows that had gross posterior displacement, four had a revision operation with a new humeral component, and a satisfactory result was eventually achieved. Radiographic examination revealed various degrees of proximal subsidence of the humeral component in 70 per cent of the elbows. However, in most of the elbows the subsidence was not progressive and was compatible with a good clinical result. In contrast, the rate of loosening of the ulnar component was low; loosening was seen in only 5 per cent of the elbows. Seventeen elbows were followed for ten years or more, and comparison of the clinical results in the intermediate period with those at the most recent review revealed that the results improved with time. Because of the number of elbows in which subsidence of the humeral component developed, we now use a humeral component with an intramedullary stem, and were no longer recommend the use of our Type-1 and Type-2 prostheses. PMID- 2312531 TI - The effect of centrifugation on the mechanical properties of cement. An in vitro total hip-arthroplasty model. AB - An in vitro total hip-arthroplasty model was evaluated to determine if centrifugation of bone cement results in greater static strength and low-cycle fatigue strength than hand-mixing. The static-failure test of the stem, cement, and simulated bone composite demonstrated that the centrifuged cement had significantly greater static strength than the hand-mixed cement. However, under low-cycle fatigue tests on the same composite models, the centrifuged and hand mixed specimens were not significantly different. PMID- 2312532 TI - Cauda equina syndrome after in situ arthrodesis for severe spondylolisthesis at the lumbosacral junction. AB - Relative stretching of the cauda equina over the posterosuperior border of the sacrum can be found in all patients who have Grade-III or IV spondylolisthesis at the lumbosacral junction. We identified twelve patients, all less than eighteen years old, who had cauda equina syndrome after in situ arthrodesis for Grade-III or IV lumbosacral spondylolisthesis. In all twelve patients, posterolateral arthrodesis had been done bilaterally through a midline or paraspinal muscle splitting approach. Nothing in the operative reports suggested that the cauda equina had been directly injured during any of the procedures. Five of the twelve patients eventually recovered completely. The remaining seven patients had a permanent residual neurological deficit, manifested by complete or partial inability to control the bowel and bladder. If dysfunction of the root of the sacral nerve is noted preoperatively in a patient who has lumbosacral spondylolisthesis, decompression of the cauda equina concomitant with the arthrodesis should be considered. An acute cauda equina syndrome that follows a seemingly uneventful in situ arthrodesis for spondylolisthesis is best treated by an immediate decompression that includes resection of the posterosuperior rim of the dome of the sacrum and the adjacent intervertebral disc. In addition, posterior insertion of instrumentation and reduction of the lumbosacral spondylolisthesis should be considered. PMID- 2312533 TI - Seasonal variation of slipped capital femoral epiphysis. AB - To correlate the season of the year with the prevalence of slipped capital femoral epiphysis, we reviewed the cases of 177 patients who had 243 slips during an eleven-year period. We assessed the month when the patient was seen and the implied time of onset of the slip and found a statistically significant variation for both. The average time of onset was mid-June, with a standard deviation of 2.5 months, and was not significantly different for race, sex, or laterality. We attributed the increased incidence of slipped capital femoral epiphysis during the summer to increased physical activity in that season. PMID- 2312534 TI - The effects of transection of the anterior cruciate ligament on healing of the medial collateral ligament. A biomechanical study of the knee in dogs. AB - The effect of concurrent injury to the anterior cruciate ligament on the healing of injuries of the medial collateral ligament was studied in dogs. In Group I, isolated transection of the medial collateral ligament was performed; in Group II, transection of the medial collateral ligament with partial transection of the anterior cruciate ligament; and in Group III, complete transection of both the medial collateral ligament and the anterior cruciate ligament. The three groups of animals were examined six and twelve weeks postoperatively with respect to varus-valgus rotation of the knee and tensile properties of the femur-medial collateral ligament-tibia complex. The varus-valgus rotation of the knee was found to be the largest in Group-III specimens at all time-periods and was 3.5 times greater than the control values at twelve weeks. Group-I and Group-II specimens also showed large varus-valgus rotations at time zero, but the rotations returned to the control values by twelve weeks. For the structural properties of the femur-medial collateral ligament-tibia complex, the values for ultimate load for Groups I and II reached the control values by twelve weeks, while that for Group III remained at only 80 per cent of the control value. Both energy absorbed at failure and linear stiffness for all three groups were less than those for the controls at six weeks, and only linear stiffness returned to the control values by twelve weeks. For the mechanical (material) properties of the healed ligament substance, the values for modulus and tensile strength were markedly lower than the control values for all groups at six weeks. By twelve weeks, the tensile strength of Group-I specimens had increased to 52 per cent of the control value, while those of Groups II and III were only 45 and 14 per cent, respectively. Our results demonstrate that healing of the transected medial collateral ligament is adversely affected by concomitant transection of the anterior cruciate ligament. Both varus-valgus rotation and mechanical properties of the healed ligament failed to recover in knees that had combined transection of the anterior cruciate and medial collateral ligaments. The structural properties of the femur-medial collateral ligament-tibia complex in tension recovered more rapidly as a consequence of the large mass of reparative tissue that formed in the medial collateral ligament of the anterior cruciate-deficient knees. PMID- 2312535 TI - Posterior transfer of the anterior tibial tendon in children who have a myelomeningocele. AB - Posterior transfer of the tendon of the anterior tibial muscle through the interosseous membrane to the calcaneus to prevent or correct a calcaneus deformity was performed in twenty patients (thirty-nine feet) who had a myelomeningocele. The average age of the patients at the time of the operation was 4.6 years, and they were followed for an average of six years. Satisfactory clinical and radiographic results were obtained in thirty-seven (95 per cent) of the thirty-nine feet. Two patients, one who was unable to walk and one who walked at home only, had a mild equinus deformity of the left foot. No patient had a clinical calcaneus deformity, but there was radiographic evidence of talipes calcaneus in one patient (two feet). The anterior tibial muscle functioned more consistently when the operation was performed after the patient was four years old and in patients who had a fifth lumbar or first sacral motor level. PMID- 2312536 TI - Management of dislocations of both ends of the clavicle. AB - We treated six patients who had a dislocation of both ends of the clavicle (an anterior dislocation of the sternoclavicular joint and a posterior dislocation of the acromioclavicular joint). Two patients who had fewer demands on the shoulder- an elderly woman and a woman who had had an ipsilateral amputation of the hand- did well; they had only minor symptoms after non-operative management. The other four patients (all men) had continuing pain at the acromioclavicular joint; each had a reconstruction of the joint, which resulted in a painless, full range of motion and return to normal activity. No patient had continuing pain in the sternoclavicular joint. PMID- 2312538 TI - Magnetic resonance imaging of vascular anatomy before vascularized fibular grafting. AB - Magnetic resonance images of the leg were made preoperatively to show the vascular anatomy in twenty-nine patients (thirty-five legs) who were between the ages of fourteen and forty-one years and in whom we planned to use the fibula as a vascular graft. The fibula was harvested as a graft in thirty-two legs, and this allowed us to compare the images with the anatomical findings at operation. In these thirty-two legs, the branching pattern, the measured distance to the bifurcation of the peroneal artery, and all vascular anomalies in the area were accurately detected. No graft was taken from the other three legs. We recommend that imaging of the vascular anatomy of the leg be done before using the fibula as a vascular graft in order to detect the precise point of origin of the peroneal artery from the posterior tibial artery, to estimate the length of the vascular pedicle, and to evaluate the role of the three major vessels in supplying blood to the leg. All these aims can be accomplished with the aid of angiography, but we have found that gradient-recalled acquisition in the steady state (GRASS) magnetic-resonance imaging is more cost-effective and is associated with less morbidity. It is not adequate for older patients who have arterial stenosis or atherosclerosis or for patients who have some other underlying vascular disease. Metallic hardware may cause artefacts that obscure the vascular anatomy. PMID- 2312537 TI - Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation. AB - We performed magnetic resonance imaging on sixty-seven individuals who had never had low-back pain, sciatica, or neurogenic claudication. The scans were interpreted independently by three neuro-radiologists who had no knowledge about the presence or absence of clinical symptoms in the subjects. About one-third of the subjects were found to have a substantial abnormality. Of those who were less than sixty years old, 20 per cent had a herniated nucleus pulposus and one had spinal stenosis. In the group that was sixty years old or older, the findings were abnormal on about 57 per cent of the scans: 36 per cent of the subjects had a herniated nucleus pulposus and 21 per cent had spinal stenosis. There was degeneration or bulging of a disc at at least one lumbar level in 35 per cent of the subjects between twenty and thirty-nine years old and in all but one of the sixty to eighty-year-old subjects. In view of these findings in asymptomatic subjects, we concluded that abnormalities on magnetic resonance images must be strictly correlated with age and any clinical signs and symptoms before operative treatment is contemplated. PMID- 2312539 TI - Spondylolisthesis treated by a single-stage operation combining decompression with in situ posterolateral and anterior fusion. An analysis of eleven patients who had long-term follow-up. AB - We treated eleven skeletally mature patients who had a high-grade lumbosacral spondylolisthesis by a single-stage operation that involved posterior spinal decompression, posterolateral arthrodesis with autogenous iliac-crest graft, and anterior arthrodesis with a fibular graft inserted from the posterior approach. We did not attempt to correct the deformity. Preoperatively, all but one patient had severe pain in the back and lower limb; the exceptional patient had severe pain only in the low back. All but one patient had sensory deficits and objective motor impairment before the operation, and five had cauda equina syndrome. Six patients had had a previous operation that had failed. The duration of follow-up ranged from two to twelve years. A solid fusion was obtained in all patients, and all had major or complete neurological recovery. The results did not deteriorate with time. PMID- 2312540 TI - Transfer of the pronator teres tendon to the tendons of the flexor digitorum profundus in tetraplegia. AB - In eleven patients who had traumatic tetraplegia, the pronator teres tendon was transferred to the flexor digitorum profundus tendons to restore active flexion of the fingers. At the same time, in ten of these patients the tendon of the brachioradialis was transferred to the tendon of the flexor pollicis longus, and in the eleventh patient the brachioradialis tendon was transferred to the tendon of the flexor digitorum superficialis of the small finger, to restore pinch. The average time between injury and operation was thirty-four months. The average length of follow-up after operation was thirty-four months. Ten patients gained functional active flexion of the fingers, and they reported improved performance of activities of daily living. When the wrist was in 30 degrees of extension, the average active grasp strength was twenty-one millimeters of mercury and the average key-pinch strength was 2.2 kilograms. The average active flexion of the fingers from the resting position, measured from the tip of the finger to the distal palmar crease, was 1.5 centimeters. Only one patient did not gain active flexion of the fingers. Of the entire group, this patient had the least function of the hand on preoperative evaluation; retrospectively, he seemed to be a poor candidate for operation, since the strength of the pronator teres muscle and the sensibility of the hand were insufficient for useful function. We concluded that, in selected tetraplegic patients, transfer of the pronator teres tendon to the flexor digitorum profundus tendons provides useful active flexion of the fingers. PMID- 2312541 TI - Arthrodesis of the knee with intramedullary nail fixation. AB - Thirty-three patients had an arthrodesis of the knee by means of an intramedullary nail introduced through the greater trochanter. Fifteen of the procedures were done for a failed knee arthroplasty; eight had failed because of infection and seven, because of aseptic loosening. Twenty-nine of the thirty three knees united three to four months after the first attempt at arthrodesis and three united after technical errors were corrected. One knee had a broken nail and a non-union; this was still untreated at the time of writing. Four nails broke: three in the line of fusion and one in the line of an infected supracondylar pseudarthrosis of the femur. No new infections developed after the arthrodesis. Three patients had had an infection and a chronic fistula before the arthrodesis, and the fistulae healed six, fourteen, and eighteen months postoperatively. In another patient, who had had infection and necrosis of the skin preoperatively, the wound healed in six months. All of these knees healed without an additional major operation. The functional result was satisfactory in all patients. After the arthrodesis, seventeen of the thirty-three patients needed less aid when walking, and no patient needed more aid. Fusion of the knee with a long intramedullary nail can be safe and effective, even in the presence of infection, if the revision is performed properly and certain technical principles are followed. It is especially important to establish good contact between the resected bones. PMID- 2312542 TI - Double closed fractures of the humerus in a child. A case report. PMID- 2312543 TI - Multiple identical stress fractures in monozygotic twins. Case report. PMID- 2312544 TI - Isolated palmar dislocation of the trapezoid associated with attritional rupture of the flexor tendon. A case report. PMID- 2312545 TI - Scaphotrapezial dislocation. A case report. PMID- 2312546 TI - Tarsal tunnel syndrome caused by the flexor digitorum accessorius longus. A case report. PMID- 2312547 TI - Total knee replacement after spontaneous osseous ankylosis. A report of three cases. PMID- 2312548 TI - Instability of the cervical spine and neurological involvement in Klippel-Feil syndrome. A case report. PMID- 2312549 TI - Rheumatoid arthritis presenting as spreading of the toes. A report of three cases. PMID- 2312550 TI - Corrective shoes and inserts as treatment for flexible flatfoot in infants and children. PMID- 2312551 TI - Total knee replacement--not a bridge too far. PMID- 2312552 TI - Early open reduction for congenital dislocation of the hip. AB - We have reviewed 82 children with congenital dislocation of the hip, after treatment by anterior open reduction followed by derotation femoral osteotomy. The clinical and radiological results were significantly better in the group that had open reduction before the appearance of the capital femoral epiphysis; this group also had a lower incidence of avascular necrosis. We conclude that, when it is clearly indicated, the earlier an open reduction is carried out the better the results. PMID- 2312553 TI - Computerised arthrotomography of primary anterior dislocation of the shoulder. AB - Computerised arthrotomography was performed on 33 patients four to six weeks after acute primary anterior dislocation of the shoulder. Seventeen patients were under, and 16 over 50 years of age. Damage to the anterior glenoidal labrum was seen in all the younger patients and in 75% of the older ones. A large redundant capsular pouch, seen in the older patients, was present in 35% of the younger ones, and a posterior humeral head defect was seen in 82% of the younger patients and only 50% of the older. Associated fractures were more common in the older patients, and a tear of the rotator cuff was demonstrated in 63% of the older patients and in none of the younger ones. PMID- 2312554 TI - Acetabular cover in congenital dislocation of the hip. AB - The exact measurement of femoral head cover is essential for an assessment of reduction of congenital dislocation of the hip. We have compared standard anteroposterior radiographs with computerised tomograms and thereby classified the shape of the acetabular roof into four types. We found that the CE angle of Wiberg is a more reliable measure of head cover when the lateral point of bony condensation of the roof is chosen as the reference point rather than the edge of the bone, where these two points do not overlap. We conclude that head cover can be more accurately determined in younger children with dysplastic hips by our 'refined' CE angle, than by the original method of Wiberg. PMID- 2312555 TI - Interobserver variability in grading Perthes' disease. AB - Fifteen independent observers of three levels of experience (consultant staff, fellows, residents) assessed 40 radiographs of children presenting with Perthes' disease using the Catterall and the Salter-Thompson grading systems. Each observer was supplied with descriptions and illustrations of the classifications and each hip was grouped by both systems by each observer. The results were statistically analysed using 'kappa' statistics. The level of interobserver agreement was higher for the Salter-Thompson system and correlated with the level of experience of the observer. Both systems can give acceptable levels of interobserver agreement, but the Salter-Thompson grouping is simpler and easier to apply in the earlier stages of the disease when treatment must be decided, and has a higher degree of reproducibility amongst more experienced observers. PMID- 2312556 TI - Cementless total replacement for severely dysplastic or dislocated hips. AB - We report the short-term results of 100 cementless total hip replacements in 52 severely dysplastic and 48 totally dislocated hips, with some new technical solutions to the problems involved. In cases with a very narrow iliac bone, the acetabular screw ring is seated below the true cotyloid area. In hips with tight flexor and abductor muscles or with deformities of the proximal femur, various osteotomies were performed. Special attention was paid to careful pre-operative planning and precise operative technique. In spite of a high complication rate the results were generally good and even patients who required reoperation were satisfied with the final result. PMID- 2312557 TI - Cementless revision of aggressive granulomatous lesions in hip replacements. AB - In 16 patients we used uncemented Lord prostheses at revision operations for aggressive granulomatosis after cemented hip arthroplasties; in 12 bone grafts also were used. In 13 hips the granulomatous lesions were multifocal, and in one the acetabular component was involved. There was no evidence of infection in any case: all the patients had normal ESR and CRP levels. The revision operation was performed on average 9.4 years after the primary replacement; the mean age at revision was 64 years. On radiographs, the bone around the prosthesis had consolidated by an average of 16 months. At follow-up, two to six years later (mean 3.5 years) there had been no recurrences, nine patients had an excellent Mayo hip score, five were good and two fair. PMID- 2312559 TI - Excision arthroplasty for infected constrained total knee replacements. AB - We have reviewed 15 patients with infected total knee replacements after removal of the prosthesis, rigorous debridement, antibiotic irrigation, and prolonged systemic antibiotics. Infection was permanently eradicated in all patients; they were left with a functioning limb, on which they could walk with either a caliper (8 patients), a simple splint (3), crutches, or sticks. Three were disappointed because of residual pain. We believe that, if exchange arthroplasty is inappropriate, this procedure is preferable to arthrodesis or amputation for persistent and disabling infection, particularly where constrained artificial joints have been used. PMID- 2312558 TI - Prophylactic pinning in slipped upper femoral epiphysis. Prevention of complications. AB - We report the complications of prophylactic pinning of slipped upper femoral epiphysis with Crawford Adams pins in 95 cases. Complications of pin placement were seen in 13.7%. Although seven hips had penetration of the joint, there were no cases of chondrolysis or avascular necrosis. Excavation of the lateral femoral cortex was required at pin removal in 12.5% of cases. Analysis of the growth around pins allowed recommendations to be made regarding pin protrusion. The use of improved fixation devices may reduce the need for multiple pins. PMID- 2312560 TI - Posterior instability of the knee near extension. A clinical and stress radiographic analysis of acute injuries of the posterior cruciate ligament. AB - We evaluated the accuracy of six clinical tests for posterior instability in 24 knees with acute surgically-proven posterior cruciate ligament injuries and intact anterior cruciate ligaments. We also performed stress radiography under anaesthesia. The gravity sign and the posterior drawer test in near extension and its passive reduction were diagnostic in 20 of the 24 knees, and the active reduction of posterior subluxation was diagnostic in 18. The reversed pivot shift sign helped to diagnose severe posterior and posterolateral subluxations, but the external rotation recurvatum test was negative in all 24 knees. Stress radiography in near extension revealed a highly significant increase in posterior tibial subluxation in the injured knees. PMID- 2312561 TI - Fracture of the tibial tubercle in the adolescent. AB - We have reviewed 16 patients with avulsion fractures of the tibial tubercle, mostly boys who sustained left-sided injuries during sport. Two-thirds had type I or II injuries and were treated conservatively. Fractures involving the knee joint (type III) had internal fixation. The final results were good except for minor complications such as a prominent and uncomfortable tibial tubercle. PMID- 2312562 TI - A simple technique for varus supracondylar osteotomy in genu valgum. AB - Varus osteotomy of the distal femur is recommended for osteoarthritis of the knee with significant valgus deformity, but the operation is difficult to plan and perform. A simple technique involving a jig referenced to the line of the tibia is described. This allows accurate overcorrection by a few degrees, with impaction and secure fixation at the osteotomy. It has been successful, with no complications, in 12 consecutive knees. PMID- 2312563 TI - High tibial osteotomy for medial osteoarthritis of the knee. A 5 to 7 and 11 year follow-up. AB - On three occasions we have reviewed a series of knees after high tibial osteotomy for osteoarthritis: 99 were reviewed at one to two years; 81 at a mean of 5.7 years; and 65 at a mean of 11.9 years. At one to two years and at 5.7 years over 50% were good and over 75% acceptable. At 11.9 years, 43% were good and 60% acceptable. We determined the mechanical axis through the knee in maximum varus and maximum valgus; significantly better results were found if a mean angulation of 3 degrees to 7 degrees of valgus had been achieved at operation. We also measured intercondylar distances under varus and valgus stress, and found no significant lateral compartment narrowing. The best results were seen in knees with pre-operative grade I or grade II osteoarthritis and valgus deviation after osteotomy. PMID- 2312564 TI - The importance of the toes in walking. AB - The importance of well-functioning toes has long been recognised but has not previously been assessed in biomechanical studies. We have examined the weight bearing function of the foot in 160 normal subjects by use of the pedobarograph. The function of the toes was assessed by reference to the time they were in contact with the ground and the peak pressures they exerted individually in comparison with other parts of the foot. The toes were in contact for about three quarters of the stance phase of gait and exerted peak pressures similar to those of the metatarsal region. When the foot was bearing the second peak of total force, the area in contact with the ground (the metatarsal heads and toes) was decreasing. PMID- 2312565 TI - The effect of a stem on the tibial component of knee arthroplasty. A roentgen stereophotogrammetric study of uncemented tibial components in the Freeman Samuelson knee arthroplasty. AB - We studied the effect of a metal tray with an intramedullary stem on the micromotion of the tibial component in total knee arthroplasty. Of 32 uncemented Freeman-Samuelson knee arthroplasties performed in London and Gothenburg, nine had a metal backing and stem added to the tibial component. Micromotion of the tibial components, expressed as migration and inducible displacement, was analysed using roentgen stereophotogrammetric analysis up to two years follow-up. The addition of a metal back and a 110 mm stem to the standard polyethylene component significantly reduced both migration over two years and inducible displacement. PMID- 2312566 TI - Severe spondylolisthesis in children and adolescents. A long-term review of fusion in situ. AB - From 1948 to 1980, 93 children and adolescents had fusion in situ for severe spondylolisthesis with a slip of 50% or more, at a mean age of 14.8 years. Of these, 52 girls and 35 boys were reviewed after a mean follow-up of 13.8 years. The mean pre-operative slip was 76% and pain frequency correlated with the severity of the lumbosacral kyphosis but not with that of the slip. Posterior fusion was used in 54, posterolateral in 30 and anterior fusion in three patients. There were no major complications but 16 had re-operations for non union or root symptoms. At follow-up there were three non-unions. After operation, 19 patients had 10% or more progression of the slip, but 10 showed correction by more than 10% as a result of remodelling. The lumbosacral kyphosis had increased by more than 10 degrees in 45%. Postoperative progression of the slip and of lumbosacral kyphosis was significantly more if the posterior element had been removed. At follow-up 77 patients were subjectively improved, four were unchanged, and one was worse. These results did not correlate with either the degree of the slip, or the angle of lumbosacral kyphosis. Fusion in situ is safe and gives good long-term clinical results. Secondary changes are associated with increased lumbosacral kyphosis, so reduction of this should be considered in severe cases. PMID- 2312568 TI - Whiplash injuries. A trial of early management. AB - We have conducted a prospective trial of the management of 135 adult patients who had sustained soft-tissue injuries of the neck in vehicle accidents. Early traction and physiotherapy was compared with rest in a collar and unsupervised mobilisation. No benefit from the active treatment could be identified; moulded collars in slight flexion gave the best pain relief and are recommended. PMID- 2312567 TI - Discitis after discography. The role of prophylactic antibiotics. AB - Discitis after discography is due to bacterial penetration into the intervertebral disc by a contaminated needle and has an incidence of 1% to 4%. We have examined the prophylactic role of cephazolin administered at the time of discography. An experimental study in sheep using radiographic contrast containing Staphylococcus epidermidis showed that either adding the antibiotic to the intradiscal suspension or giving it intravenously 30 minutes before intradiscal inoculation of bacteria prevented any radiographic, macroscopic or histological signs of discitis; all the intervertebral disc cultures were negative. In a prospective clinical study of 127 consecutive patients having lumbar discography, the injected contrast contained cephazolin 1 mg per ml. None of the patients developed clinical or radiographic signs of discitis. We recommend the use of a suitable broad spectrum antibiotic in a single prophylactic dose whenever the intervertebral disc is entered. PMID- 2312569 TI - Internal fixation for fractures of the patella. A comparison of two methods. AB - Cadaveric experiments in 10 knees were used to study the strength of two methods of internal fixation for a fractured patella. A modified AO tension band technique was compared with the combination of cerclage wiring and a tension band used at Pyrford. The repairs were stressed to failure; the combination of cerclage and tension band wiring proved to be significantly stronger and is recommended. PMID- 2312570 TI - Functional bracing for comminuted extra-articular fractures of the distal third of the humerus. AB - From 1982 to 1987 we treated 85 extra-articular comminuted distal third humeral fractures in adults with prefabricated plastic braces. Of these, 15% were open fractures and 18% had initial peripheral nerve injury. On average, the sleeve was applied 12 days after injury and used for 10 weeks. There was 96% union, with no infections. All nerve injuries resolved or were improving at the latest examination. At union there was varus deformity averaging 9 degrees in 81% of patients, but loss of range of movement was minimal and functional results were good. PMID- 2312571 TI - The timing of amputation for lower limb trauma. AB - We reviewed 35 patients who had an amputation following the failure of treatment for severe lower limb trauma. Seven of the amputations were for ischaemia, within one month of injury; 13 were between one month and one year for infection complicating loss of wound cover in un-united fractures; and 15 were later than one year after injury, mainly for infected non-union. The latter group of patients had had an average of 12 operations and 50 months of treatment, including eight months in hospital. We used a new limb injury score based on damage to the individual tissue elements; this indicated that, even in the absence of neurovascular injury, the presence of severe damage to skin, bone and muscle, with wound contamination, particularly in the lower tibia, had a poor prognosis. We therefore recommend, to avoid multiple operations, with prolonged hospitalisation and suffering, that these patients should have early independent review by orthopaedic and plastic surgeons with the aim of establishing an accurate prognosis for the salvage of a useful limb. PMID- 2312572 TI - The effect of tenotomy and immobilisation on intramuscular connective tissue. A morphometric and microscopic study in rat calf muscles. AB - The effect of tenotomy and of immobilisation in lengthened and shortened positions on the intramuscular connective tissue of the calf muscles of the rat was studied morphometrically and with a scanning electron microscope. Both tenotomy and immobilisation produced a marked increase in both the endomysial and the perimysial collagen networks, with a simultaneous decrease in intramuscular capillary density. The increase in connective tissue volume was more pronounced and occurred more rapidly in the soleus, which consists mainly of type I, slow twitch fibres than in the gastrocnemius, which is mainly of type II, fast-twitch fibres. The relative volume of connective tissue increased in parallel with the duration of immobilisation or after tenotomy. There was slightly more increase after immobilisation in a shortened rather than in a lengthened position. PMID- 2312573 TI - The relationship between periosteal division and compression or distraction of the growth plate. An experimental study in the rabbit. AB - We subjected the proximal tibial growth plates of six-week-old rabbits to either compression or distraction of 1 kg on both legs. On one side the proximal tibial periosteum was divided circumferentially and stripped for 1 cm. After six weeks, growth was measured at both proximal and distal growth plates. Compression inhibited total tibial growth and distraction enhanced it. The compressed growth plate grew less and the distracted growth plate grew more, but there was a reciprocal change at the other end of the bone. Periosteal division enhanced growth at the adjacent growth plate but inhibited it distally; the effect of distraction was enhanced and that of compression reduced. We found reciprocal growth rates at the proximal and distal growth plates. Relatively small amounts of compression or distraction did affect total bone growth. Periosteal division appeared to induce overgrowth at least partly by a mechanical effect; it may be useful as an adjunct to other methods of leg lengthening, though not to epiphyseolysis. PMID- 2312574 TI - Effect of postoperative radiation on the incorporation of tibial bone grafts in the rabbit. AB - A dose of 48 Gy of X-irradiation given over two to five weeks after grafting caused no significant delay in the rate of healing and only a small and statistically non-significant decrease in the torsional strength of the graft bone junction of either vascularised or non-vascularised bone grafts of the tibiae of rabbits. Healing was faster and the union between the graft and adjacent bone developed torsional strength significantly more rapidly with vascularised than with non-vascularised grafts. These findings suggest that postoperative radiotherapy is unlikely to have a significantly deleterious effect on the healing of bone grafts used to repair defects produced by excision of malignant bone tumours. PMID- 2312575 TI - A new type of peripheral nerve lesion. AB - We report a hitherto undescribed type of peripheral nerve lesion in which pressure results in mechanical demyelinisation of a length of nerve with interruption of conduction. On release of the pressure, early recovery may follow the return of the myelin insulation. PMID- 2312576 TI - The coracoid impingement syndrome. AB - Coracoid impingement results from encroachment on the coracohumeral space, presenting as anterior shoulder pain and clicking, particularly in forward flexion, medial rotation, and adduction. In eight shoulders in seven patients, coracohumeral decompression by excision of the lateral 1.5 cm of the coracoid with re-attachment of the conjoined tendon gave pain relief in all, and complete relief in six. This procedure is described and recommended. PMID- 2312577 TI - The closed reduction of trochanteric fractures. PMID- 2312578 TI - Closed nailing of a femoral fracture followed by sciatic nerve palsy. PMID- 2312579 TI - A rare cause of brachial artery injury. PMID- 2312580 TI - Stable osteochondritis dissecans--does the lesion unite? PMID- 2312581 TI - Entrapment of the proximal fragment of supracondylar fractures. PMID- 2312582 TI - Intraneural haemangioma of the posterior tibial nerve. PMID- 2312583 TI - Tooth loss and hip fractures in the elderly. PMID- 2312584 TI - Secondary screening for congenital displacement of the hip. PMID- 2312585 TI - Traumatic hemipelvectomy without visceral injury. PMID- 2312586 TI - Sternal osteomyelitis in drug addicts. PMID- 2312587 TI - Replacement of full-thickness burns on mice with isogeneic skin equivalents. AB - A copper slug heated with a soldering iron was used to produce full- and partial thickness burns on the backs of mice. The untreated partial-thickness burns healed by outgrowth of epidermal cells from the hair follicles and adjoining skin, and the full-thickness burns formed linear scars. Skin equivalents containing isogeneic fibroblasts and epidermal cells were used to replace full thickness burns; these grafts were fully vascularized and covered with a cornified epidermis within 2 weeks. The grafts maintained 34% of their original area at 180 days, but the full-thickness burns retained only 4.5% of the initial area. For the first 2 weeks, the splenic index in animals that received burns followed by surgical excision and grafting was significantly greater than in the animals that had burns not followed by excision, but the difference was no longer significant by 21 days. PMID- 2312589 TI - Obesity: a risk factor in the burn patient. AB - Obesity is seldom recognized as a risk factor for the patient with burns. However, the overweight patient with burns presents major problems for the burn team, especially in the areas of wound care, pulmonary care, and general nursing care. One-hundred eighty adults (9.1% weighed more than 45 kg above ideal body weight or more than 100 kg in total weight. Mean weight was 110 kg, with 155 patients heavier than 100 kg. Mean age was 38 years with a mean burn size of 26% (11% full-thickness). The mortality rate was 21%, and respiratory and cardiovascular complications occurred in 33% of these patients. The obese patient presents problems disproportionate to burn size, burn location, and age. The obese patient's problems are related to weight. Care is often compromised by the physical constraints of a patient's size. PMID- 2312588 TI - A new surgical procedure for aged burn victims: applications of dermolipectomy for burn wounds and donor sites. AB - A new surgical method for use on both burn wounds and donor sites of elderly patients with burns is presented. This procedure is based on dermolipectomy. During the period from January 1985 to December 1988, 20 operations were performed on 18 patients. This procedure was applied to 39 donor sites and to four burn wound sites. The most common donor site was the lateral trunk. There was only one postoperative death. Actual survival rates and predicted survival rates were compared, and in those patients with burns over 21% to 40% of total body surface area actual survival rates were better than the predicted rates. PMID- 2312590 TI - Combined ionizing radiation and thermal injury in the rat. Evaluation of early excision and closure of the burn wound. AB - The present study was undertaken to establish an animal model of combined whole body irradiation and thermal injury and to determine the effectiveness of early excision and closure of the burn wound in such a model. Whole-body irradiation over a range of doses resulted in a predictable mortality rate, with an LD50/30 of 783 rad with 95% confidence limits of 737 and 823 rad. A controlled 10% body surface area full-thickness thermal injury resulted in no deaths in 30 animals. When combined with a standard nonlethal 10% thermal injury, varying doses of whole-body irradiation resulted in widely differing LD50/30 values in three separate cohorts of rats. Excision and closure of a 10% burn 24 hours after exposure to 200 rads did not improve survival. (J BURN CARE REHABIL 1990;11:42-5) PMID- 2312591 TI - Reconstruction of the oral commissure after an electrical burn. AB - A burn of the oral commissure is one of the most common types of electrical injury in children. To minimize postoperative wound contracture in late reconstructive surgery, a functional reconstruction that combines excision of the burn scar with lateral advancement of the orbicularis oris muscle, re-creation of the modiolus labii, and reestablishment of vermilion continuity has been developed. Functional restoration of the labial musculature to the preinjury position with re-creation of the modiolus labii and reestablishment of vermilion continuity appears to significantly decrease the amount of postoperative wound contracture (p less than 0.025). PMID- 2312592 TI - The management of burns to the perineum and genitals. AB - A review of 1987 patients treated during the years 1981 to 1986 was conducted to answer the following questions about perineal burns: (1) Are Foley catheters necessary for all patients? (2) Is there any advantage to early excision of the perineal burn wound? (3) What are the complications of perineal wounds? One hundred three patients with perineal burns were identified; mean burn size was 36% of total body surface area. There were 29 deaths in this group but none were related to the perineal burns. Of the 74 survivors 36 (49%) needed Foley catheters. However, the catheters were in place for the period of resuscitation only. There were no urethral complications associated with catheterization. Only three patients required surgery: one had a urethral meatotomy and two had split thickness skin grafts. In conclusion, we found no genitourinary complications associated with perineal burns. Almost all perineal and genital burns were managed without indwelling catheters. Early excision of the perineal burn wound is not necessary, and most of these wounds will heal satisfactorily without grafting. PMID- 2312593 TI - Restoration of play in a severely burned three-year-old child. AB - The critical importance of play in a child's life and, more specifically, to successful adaptation to trauma and disability is illustrated in the case report of a severely burned 3-year-old. Loss of interest in play is frequently seen in depressed children and in children whose physical ability to play has been constrained by physical illness, injury, or acquired disability. Play is important to the development of cognition, affectivity, and social learning, dimensions central to coping behavior. The aim of therapeutic treatment of a child whose interest in and ability to play have significantly declined is to physically and psychologically mobilize the patient to restore play and to free up the emotions, enhancing the child's ability to actively participate in and optimally benefit from the rehabilitation program. Clinical analysis of a 3-year old's symbolic play and therapeutic interventions are presented. PMID- 2312594 TI - Delayed autograft loss in HIV-positive patients: two cases. AB - Two cases that show delayed autograft loss secondary to late polymicrobial infection in patients whose test results are positive for the human immunodeficiency virus (HIV-positive patients) are presented. Mechanisms of immune dysfunction in HIV-positive patients are reviewed, and speculation on the possible contribution of polymorphonuclear or other immune dysfunction to the graft failure in these patients is presented. Questions are raised regarding the prognostic importance of HIV positivity in patients with burns and the need for special surgical considerations in these patients. The issue of transmissibility of HIV in the burn unit setting is addressed, and infection control is discussed. PMID- 2312595 TI - The use of a modified tonometer in burn scar therapy. AB - We report on the use of a modified Schiotz tonometer to evaluate the effects of therapies on burn scars. It is now possible to quantify the course of cicatrization with tonometry. Because tonometry affords a precise evaluation of burn scar diagnosis and prognosis, it is possible to avoid arbitrary clinical evaluation of the burn scarring process. PMID- 2312596 TI - The burn surgeon and the need for critical care certification. PMID- 2312597 TI - Should burn blister fluid be evacuated? PMID- 2312598 TI - Post-traumatic stress disorder. PMID- 2312599 TI - Chronic myelogenous leukemia: an overview. PMID- 2312601 TI - Progress in treatment of testicular cancer. PMID- 2312600 TI - Multiple myeloma: biology and therapy. PMID- 2312602 TI - Combination chemotherapy of advanced medullary and differentiated thyroid cancer. Phase II study. AB - A group of 20 patients with advanced medullary (MTC) or differentiated thyroid carcinoma (DTC) received a combination chemotherapy of doxorubicin (50 mg/m2), cisplatin (60 mg/m2) and vindesine (3 mg/m2). In the 18 (10 MTC, 8 DTC) evaluable patients only 1 partial remission (in a patient with MTC) and 3 minor responses (in 3 patients with DTC) were observed. These responses lasted for 15, 9, 13, and 22 months, respectively. Three MTC patients suffered from progressive disease and "no change" was seen in the other 11 patients. Toxicity, including 1 severe case of cardiomyopathy, was considerable. Thus, the combination chemotherapy of doxorubicin, cisplatin and vindesine has failed to prove superior to the commonly applied doxorubicin monotherapy in patients with advanced medullary or differentiated thyroid carcinoma. PMID- 2312603 TI - Sequential study on spontaneous colony formation by bone marrow cells during butylnitrosourea-induced leukemogenesis in the rat. AB - The spontaneous colony (SC)-forming activity of bone marrow cells of rats during butylnitrosourea (BNU) treatment was studied sequentially in an attempt to analyze stages of leukemogenesis. Aspirated bone marrow cells from female Sprague Dawley (SD) rats that had been given continuous access to drinking water containing 400 ppm BNU were examined at intervals of 3-5 weeks for colony formation of granulomonocytic cells with or without supplemental colony stimulating factor (CSF). Granulocytic leukemia was first observed at week 12, and the cumulative incidence reached 80% by week 30. SCs were obtained in 56% of rats in the early stage (3 weeks) and in up to 59% of rats in the late stages (20 25 weeks). However, in the middle stages colony formation was rare, even with the addition of CSF. When adherent cells were removed from the bone marrow cells, the SC-forming activity in the early stage was almost entirely lost, whereas much of that in the late stage remained. It is possible that in the former case, overproduction of endogenous CSF by adherent cells under the influence of BNU treatment could be involved. In contrast, late stage SC formation may be associated with the generation of altered cells, including leukemic or preleukemic elements, which have increased capacity for autonomous growth. The loss of SC-forming activity in the middle stage appeared to be attributable to an extreme reduction in endogenous CSF due to marked devastation of the bone marrow. Technical improvement in adjusting more precisely the level of CSF in the culture medium is required to enable further analysis of leukemogenesis, focused on the colony-forming activity of target cells. PMID- 2312605 TI - D-14 monoclonal antibody to carcinoembryonic antigen: immunohistochemical analysis of formalin-fixed, paraffin-embedded human colorectal carcinoma, tumors of non-colorectal origin and normal tissues. AB - The reactivity of D-14 monoclonal antibody (mAb) to a specific epitope of carcinoembryonic antigen (CEA) was evaluated on formalin-fixed, paraffin-embedded tissues. A total of 52 normal tissues, 90 colorectal carcinomas and 127 non colorectal neoplasms were tested using the peroxidase/antiperoxidase technique. D 14 mAb did not react with normal tissues apart from producing a weak staining of normal colonic glands immediately adjacent to the neoplastic structures. All 61 primary and 29 metastatic colorectal carcinomas expressed the carcinoembryonic antigen. However, there was considerable heterogeneity in cellular antigen expression in both primary and metastatic colorectal carcinomas with 10%-99% of tumor cells staining. Of 22 stomach adenocarcinomas, 14 were also immunoreactive, as were 2 of 5 pancreatic carcinomas. Only 6 of 100 neoplasms of non gastrointestinal origin expressed weak to moderate immunoreactivity. In 7 cases, colorectal micrometastases not recognized in conventional hematoxylin and eosin slides could be identified with D-14 mAb. The specificity of this antibody could be used in differentiating colorectal carcinomas from other types of tumors, including adenocarcinoma from other sites. PMID- 2312604 TI - Mucin histochemistry of virus-induced duodenal adenomas in guinea fowl. AB - The type of mucoproteins in virus-induced duodenal adenomas in guinea fowl were compared with those in the normal duodenal mucosa. The mucin-producing cells in the latter contained a mixture of acid and neutral mucins. Neutral and sulphomucins prevailed in the crypts and in the lower part of the villi, while the amount of the sialomucins increased progressively toward the tip of the villi. In the adenomas, goblet cells were more numerous and were unevenly distributed. In their mucin profile the deeply located tumor glandular structures resembled normal crypts and lower parts of the villi and superficial portions of the adenomas were similar to the upper part of the villi. Qualitative changes in the mucin secretion with deviation from the normal vertical distribution of mucin types were rarely observed. The histochemical study carried out supplemented the histological characterization of the virus-induced duodenal adenomas and contributed to the elucidation of some aspects of their histogenesis. PMID- 2312606 TI - The status of trypsin-like enzymes in squamous-cell carcinoma of the head and neck region. AB - The activity of two proteases associated with tumour cells was studied using frozen sections of squamous-cell carcinoma and fluorescent probes for the enzymes. Four fluorescent probes were used to define the enzymic status of guanidinobenzoatase on the surface of the squamous carcinoma cells. Each of four probes demonstrated the location of cells possessing inactive guanidinobenzoatase, whereas adjacent cells of the same tumour exhibited active enzyme. It was shown that the inactive form of the enzyme was an inhibitor-enzyme complex that could be dissociated. In contrast, all of the squamous carcinoma cells possessed active trypsin-like enzymes that were recognised by fluorescent aprotinin molecules. The observed variation in enzymic status of these two tumour associated enzyme systems is discussed in the context of a possible biological control mechanism for cell migration. PMID- 2312607 TI - Misinterpretation of iodine uptake in papillary thyroid carcinoma and primary lung adenocarcinoma. AB - This is the first case report of an iodine-storing metastasising carcinoma of extrathyroidal origin and the simultaneous presence of a papillary thyroid carcinoma. In the course of the disease, an increase in pathological iodine uptake was observed after repeated iodine-131 ablation, so that the original tentative diagnosis of a metastasising, differentiated thyroid carcinoma appeared to be confirmed; moreover, the histological work-up of a femur metastasis- without adequate immunohistochemical assessment--was misinterpreted. What is also remarkable about this case report is a pathological iodine-131 uptake both in the extrathyroidal primary tumor and the metastases. PMID- 2312608 TI - Prognostic implications of DNA ploidy in squamous cell carcinomas of the tongue assessed by flow cytometry. AB - A total of 47 primary squamous cell carcinomas of the tongue were analysed by DNA flow cytometry. With respect to their clonal DNA content two distinct tumor groups could be distinguished. In 14 cases the tumors (29.8%) were dipoid, whereas in 33 cases (70.2%) additional cell lines characterized by abnormal DNA content could be detected. A significant increase of aneuploid cases with tumor size as well as with decreasing histological differentiation could be detected. Aneuploid cell lines are lacking in T1 as well as in most G1 carcinomas but predominate in T3 and G3. Furthermore, cervical lymph node involvement was recognized in the majority of aneuploid primary carcinomas (81.8%) but was largely lacking in diploid tumors (21.4%). Hence, the presence of aneuploid cell lines is clearly connected with clinical and histopathological parameters, each of which have turned out to worsen the prognosis in tongue carcinomas. PMID- 2312609 TI - Comprehensive epidemiological and clinicopathological survey of Hodgkin's disease in Hungary. AB - To determine the epidemiological pattern and some clinicopathological features of Hodgkin's disease in Hungary, the data of 233 consecutive patients with the disease from seven counties, diagnosed between January 1983 and July 1987, were analysed on the basis of data from four cancer centers. Large variations were noted in incidence rates between the different regions of Hungary. The epidemiological pattern seems to vary from those reported in developed and developing countries. A sharp rise in the incidence of Hodgkin's disease occurred at the end of the second decade of patients' lives. More of our Hodgkin's patients are at advanced clinical stages, with systemic symptoms and a histological type of mixed cellularity, at the time of diagnosis, than in the western hemisphere. On the average, there is a 6-month period between the appearance of the first sign or symptom and the diagnosis. There is a lack of data outlining the epidemiological differences in the pattern of Central Europa. The aim of this study is to supply data for the etiopathogenetic research of Hodgkin's disease, as there is an important task to improve the unfavourable home situation, and to strive for earlier diagnosis in this disease. PMID- 2312610 TI - Acute leukemias in adults: an overview of recent strategies. AB - In 1989, 65%-75% of previously untreated adults with ALL or AML may be expected to enter complete remission. Approximately 40% of these completely responding patients, whether they are treated with intensive chemotherapy, intensive chemotherapy followed by autologous bone marrow transplantation, or allogeneic bone marrow transplantation, remain disease-free after 3 years of follow-up. As such, the likelihood for cure for adults with acute leukemia is approximately 25% 30%. At the present time, no new chemotherapeutic agents of significant importance are on the horizon. Furthermore, it seems doubtful that the mere juggling of drug doses will have any measurable effect on treatment outcome. The use of hematopoietic growth factors, either to allow added tolerance of intensive therapy or to synchronize leukemic cells kinetically, is now under study. Perhaps the most promising area of present investigations deals with immune manipulation. The administration of immunotoxins (a drug or a cell poison chemically linked to a leukemia-related monoclonal antibody) has been associated with promising results in eradicating minimal residual disease in animal model systems. Similarly, attempts at harnessing the graft-versus-leukemia effect without the eligibility restrictions and toxicities associated with the allograft procedure, through the use of lymphokines as enhancers of natural killer cell activity, have also proven to be effective in pre-clinical trials. With the availability of hematopoietic growth factors, immunotoxins, and lymphokines, clinical research in acute leukemia in the future will no longer focus on cytotoxic drugs alone but rather on how the addition of biological agents can prolong the duration of complete remission and increase the potential for cure. PMID- 2312611 TI - Morphologic changes in human carcinoma cells (A-431) stimulated by epidermal growth factor: effect of cholesterol and low-density lipoproteins on the ruffling response. AB - Stimulation of A-431 carcinoma cells with epidermal growth factor (EGF) causes dramatic morphologic responses including ruffling, rounding, and bulk-phase pinocytosis. In attempts to explore the mechanisms responsible for changes in plasmalemma topography, we have investigated the effects of exogenous sterols thought to alter membrane fluidity. Light and scanning electron microscopy revealed a time- and concentration-dependent inhibition of ruffling (greater than 90%) by cholesterol. This effect could be duplicated by preincubation of the cells with comparable levels of low-density lipoproteins (LDL). EGF-stimulated bulk-phase endocytosis also is inhibited by treatment with cholesterol. No alteration of EGF binding, kinase stimulation, or internalization was detected in cells incubated in cholesterol-enriched medium (175 micrograms/ml in 0.5% ethanol), nor did cholesterol or LDL have any effect on EGF-stimulated rounding. Morphometry of electron micrographs from cholesterol-treated cells revealed a selective depletion of interdigitating lateral surface membrane that normally appears to be recruited to generate apical ruffles. Thus, the sterol inhibition of ruffling may be due to redistribution of plasmalemma rather than to changes in membrane viscosity. Together with previous observations, these data suggest that EGF-stimulated ruffling and bulk-phase pinocytosis are related phenomena, whereas EGF-stimulated cell rounding is an independent process. PMID- 2312612 TI - Protein kinase C levels and protein phosphorylation associated with inhibition of proliferation in a murine macrophage tumor. AB - Treatment of M5076 tumor cells with the phorbol estes 12-O-tetradecanoylphorbol 13-acetate (TPA) and phorbol 12,13 dibutyrate (PdBu) inhibited cellular proliferation, whereas 1,2-dioctanoyl-glycerol (DiC8) and 1-oleoyl2-acetyl glycerol (OAG) did not affect cell growth. Inhibition of cellular proliferation in this cell line appears to be a consequence of protein kinase C (PKC) down regulation since phorbol esters, but not a single application of diacylglycerols (DGs) down-regulated cellular PKC levels. By repeated application of DGs, PKC down-regulation was achieved and correlated with inhibition of proliferation. Phorbol ester-induced PKC down-regulation was reversible, upon removal of the phorbol ester, and the reappearance of PKC was associated with resumption of proliferation. The mitogenic responsiveness of these cells to added serum depended upon cellular PKC levels. Phorbol esters also caused the phosphorylation of two proteins which were not phosphorylated in response to DG treatment. Inhibition of growth of M5076 cells appears to be associated with phosphorylation of two novel proteins and/or PKC down-regulation. PMID- 2312613 TI - Tumor promoters retard the loss of a transient subpopulation of cells in low passage Syrian hamster cell cultures. AB - Early passage normal diploid Syrian hamster (SH) fetal cell cultures contain a transient subpopulation of contact-insensitive (CS-) cells which lack density dependent inhibition of cell division. The size of this CS- subpopulation decreases during in vitro passage by conversion of the CS- cells to contact sensitive (CS+) cells. Approximately 10-15 population doublings after the frequency of the CS- cells has declined to below 0.001%, mass cultures cease proliferating and exhibit cellular senescence. Cultures with higher initial numbers of CS- cells exhibit longer in vitro proliferative life spans than cultures with smaller initial numbers of CS- cells. Active tumor promoting phorbol esters (12-O-tetra-decanoyl-phorbol-13-acetate [TPA] and phorbol-12,13 didecanoate [PDD]) retard the decline in the proportion of CS- cells during in vitro passage, while the inactive tumor promoting phorbol ester, 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD) has no effect on the rate of loss of the CS- cells. In addition, continuous treatment from secondary culture with TPA or PDD extends by approximately twofold the in vitro proliferative life span of SH fetal cell cultures. Treatment must, however, begin at passage 1 or 2 when the CS- cells are still present. After the proportion of the CS- cells has decreased to less than 0.001% as in passage 6 cultures, promoters have no effect on the life span of the culture. This finding that exposure to promoters results in both a prolonged maintenance of the CS- cellular subpopulation, as well as an extension of in vitro proliferative life span, suggests that the conversion of CS- cells to CS+ cells is involved in the mechanism of in vitro senescence. PMID- 2312615 TI - Three distinct effects of SV40 T-antigen gene transfection on cellular differentiation. AB - SV40 large T-antigen-induced transformation has been reported to block differentiation, but the mechanism(s) of this effect has not been established. The results presented here show that stable transfection of the SV40 T-antigen gene, via the pSV3neo plasmid, has at least three distinct effects on 3T3T adipocyte differentiation. Cells first show a decreased ability to undergo predifferentiation growth arrest, which is a prerequisite for in vitro 3T3T adipocyte differentiation. However, if predifferentiation growth arrest is accomplished by use of stringent differentiation-inducing culture conditions, adipocyte differentiation can occur with high frequency. The pSV3neo-transfected cell clones also show other modifications of the adipocyte differentiation process, including changes in nonterminal (reversible) and terminal (irreversible) steps of adipocyte differentiation. When compared to nontransfected 3T3T cells, the cell clones containing pSV3neo require markedly reduced growth factor concentrations to restimulate proliferation of nonterminally differentiated adipocytes and the terminal step of differentiation is also blocked. These results suggest that integration of the T-antigen gene, through pSV3neo transfection, has multiple effects on the cellular mechanisms of differentiation. It does not block the differentiation process per se; rather it appears to make cells highly sensitive to proliferation signals, thereby making differentiation more difficult. PMID- 2312614 TI - Effect of K+ channel-blockers on sugar uptake by isolated chicken enterocytes. AB - The effects of Ba2+, quinine, verapamil, and Ca2(+)-free saline solutions on sugar active transport have been investigated in isolated chicken enterocytes. Ba2+, quinine, and verapamil, which have been shown to inhibit Ca2(+)-activated K+ channels, decreased basal and theophylline-dependent 3-O-methylglucose (3-O MG) accumulation. Ca2(+)-free conditions reduced 3-O-MG uptake in theophylline treated enterocytes, but it had no effect in control cells. On the other hand, the uptake of a non-actively transported sugar, 2-deoxyglucose (2-DOG), by control or theophylline-treated cells was not modified by the presence of verapamil or by Ca2(+)-removal. 3-O-MG increased ouabain-sensitive Na(+)-efflux, but had no effect on either K+ efflux or K+ uptake. However, in the presence of Ba2+, K+ uptake was stimulated by 3-O-MG, and this increase was prevented by ouabain. All these findings are discussed in terms of the role that K+ permeability may play in cellular homeostasis during sugar active transport. PMID- 2312616 TI - Osmotic and motional properties of intracellular water as influenced by osmotic swelling and shrinkage of Xenopus oocytes. AB - Experiments were done on fully grown Xenopus oocytes to determine the extent and the properties of cellular water of hydration. The studies involved the osmotic shrinking and swelling of the oocytes under known osmotic pressure as well as proton NMR spectral, titration, and free induction decay analyses. Studies were done both on whole oocytes and on subcellular fractions. The results show that little if any of the oocyte water in situ has the motional or osmotic properties expected of pure "bulk" water. Four distinct water of hydration compartments were found and defined on the basis of distinct hydrogen bounding mechanisms. Some of the water in yolk platelets was found not to be in fast exchange with other water compartments. Osmotic shrinkage of oocytes caused an adaptive decrease in the bound water of hydration compartments. This osmotically induced decrease is attributed to decreased surface area available for the hydrogen bounding of water molecules on cellular proteins. PMID- 2312617 TI - Correlation between contractility and proliferation in human fibroblasts. AB - The contractile power of human fibroblasts was checked through their life span in vitro, using a plasma clot retraction test. It was found to decline with a pattern analogous to that of the different phases identifiable by the study of the kinetics of proliferation of these cells. The capacity to retract a plasma clot was higher in cells harvested during active growth than in cells harvested in resting phase. The decreased ability to retract during aging becomes apparent when cells are harvested in resting phase. Decreased retractile activity was also observed in postnatal cells as compared with embryonic cells. The results support a correlation between the initiation of DNA synthesis and the turnover of cytoskeletal elements. The data fit our previous results showing that the early proliferative disturbance during cellular senescence consists of a decline in the probability of initiating the division cycle linked to impaired cell attachment and spreading. PMID- 2312618 TI - Altered synthesis of the 26-kDa heat stress protein family and thermotolerance in cell lines with elevated levels of calcium-binding proteins. AB - Using a bovine papilloma virus-based vector, mouse mammary adenocarcinoma cells have been transformed to express elevated amounts of functional calmodulin (CaM) (Rasmussen and Means, 1987) and another Ca2(+)-binding protein, parvalbumin (PV) (Rasmussen and Means, 1989) that is not normally synthesized in these cells. Parental cells (C127) and cells transformed by the vector alone (BPV-1), the vector containing a CaM gene (CM-1), or the vector containing parvalbumin (PV-1) were used to study the effect of increased synthesis of Ca2(+)-binding proteins on heat-stress protein (HSP) synthesis and cell survival following heating at 43 degrees C. The induction, stability, and repression of the synthesis of most HSPs after 43 degrees C heating was not significantly affected by increased amounts of Ca2(+)-binding proteins, but the rate of synthesis of all three isoforms of the 26-kDa HSP (HSP26) was greatly reduced. C127 cells, which have about one half as much CaM as do BPV-1 cells, synthesized the most HSP26. CM-1 cells, which have more than fourfold higher levels of CaM than do BPV-1 cells, had a rate of synthesis of HSP26 approaching that of unheated cells. BPV-1 cells, with a two fold increase in CaM, were intermediate in HSP26 synthesis. This effect on HSP26 synthesis may be largely related to the Ca2(+)-binding capacity of CaM rather than to a specific CaM-regulated function, since PV-1 cells also showed reduced rates of HSP26 synthesis. Survival experiments showed that reduced HSP26 synthesis in cells with increased amounts of Ca2(+)-binding proteins did not significantly alter intrinsic resistance to continuous 43 degrees C heating. Thermotolerance was not reduced and appeared to develop more rapidly in CM-1 and PV-1 cells. These results suggest that (1) the signal for HSP26 synthesis can be largely abrogated by elevated Ca2+ binding protein levels, and (2) if these HSPs are involved in thermotolerance development, that function may be associated with intracellular Ca2+ homeostasis. PMID- 2312619 TI - Increased thermostability of thermotolerant CHL V79 cells as determined by differential scanning calorimetry. AB - Heat shock denatures cellular protein and induces both a state of acquired thermotolerance, defined as resistance to a subsequent heat shock, and the synthesis of a category of proteins referred to as heat-shock proteins (HSPs). Thermotolerance may be due to the stabilization of thermolabile proteins that would ordinarily denature during heat shock, either by HSPs or some other factors. We show by differential scanning calorimetry (DSC) that mild heat shock irreversibly denatures a small fraction of Chinese hamster lung V79-WNRE cell protein (i.e., the enthalpy change, which is proportional to denaturation, on scanning to 45 degrees C at 1 degree C/min is approximately 2.3% of the total calorimetric enthalpy). Thermostability, defined by the extent of denaturation during heat shock and determined from DSC scans of whole cells, increases as the V79 cells become thermotolerant. Cellular stabilization appears to be due to an increase in the denaturation temperature of the most thermolabile proteins; there is no increase in the denaturation temperatures of the most thermally resistant proteins, i.e., those denaturing above 65 degrees C. Cellular stabilization is also observed in the presence of glycerol, which is known to increase resistance to heat shock and to stabilize proteins in vitro. A model is presented, based on a direct relationship between the extent of hyperthermic killing and the denaturation or inactivation of a critical target that defines the rate-limiting step in killing, which predicts a transition temperature (Tm) of the critical target for control V79-WNRE cells of 46.0 degrees C and a Tm of 47.3 degrees C for thermotolerant cells. This shift of 1.3 degrees C is consistent with the degree of stabilization detected by DSC. PMID- 2312620 TI - Platelet-derived growth factor regulates actin isoform expression and growth state in cultured rat aortic smooth muscle cells. AB - The role of platelet-derived growth factor (PDGF) in the control of smooth muscle cell (SMC) differentiation was explored in vitro by examining its effects on expression of the smooth muscle (SM) specific contractile protein SM alpha actin in cultured rat aortic SMC. Quiescent, postconfluent SMC express maximal levels of alpha actin and responded to human platelet-derived growth factor (partially purified from platelets) by entering the cell cycle and undergoing approximately one synchronous round of DNA synthesis. Concomitantly, these cultures exhibited a marked reduction in alpha actin synthesis. Chronic treatment with PDGF (72 hours at 8 or 12 hour intervals) was associated with a transient increase in thymidine labeling index and a decrease in alpha actin expression. Interestingly, between 48 and 72 hours following initial treatment, thymidine labeling indices returned to near control levels while SM alpha actin expression remained depressed. This effect was reversible; fractional alpha actin synthesis increased immediately after PDGF removal. When subsequently stimulated with 10% fetal bovine serum (FBS), cells chronically pretreated with PDGF entered S phase approximately 4 hours earlier than cells pretreated with PDGF vehicle, consistent with the idea that the maintained suppression of alpha actin synthesis in SMC subjected to chronic PDGF treatment was associated with partial cell cycle transit. Chronic treatment with highly purified recombinant PDGF-BB elicited similar effects on alpha actin synthesis and partial cell cycle transit. Flow cytometric analysis of chronic PDGF-treated SMC demonstrated a 25% increase in forward angle light scatter, an index of cell size. These data implicate a possible role for PDGF in regulation of SMC differentiation and suggest a potentially important role for this mitogen in the phenotypic modulation accompanying SMC growth and in mediation of the cellular hypertrophy associated with cell cycle progression. PMID- 2312621 TI - Prosthetic substitution for fingernails. AB - The loss of a fingernail is remarkably disturbing to many patients. Despite all efforts, surgical methods of replacement have not proven to be very satisfactory. Like artificial eyes, techniques for making an artificial fingernail of good likeness have been available for many years. The problem has been a satisfactory method of attaching the artificial fingernail to the digit and eventually that of making the artificial nail sufficiently thin. While no perfect solution exists, the development of a "submini" digital prosthesis that covers only the distal phalanx offers the best available solution. Only if the prosthesis is custom developed and fabricated to the very highest standards will the potential be realized. Repair will be required occasionally, so assured availability of prompt and reliable maintenance services is most important. When there has been loss of tissues from the distal phalanx, the prosthesis can also help with that problem. Finally, the prosthesis has the advantage of inflicting no scars or other irreversible measures. PMID- 2312623 TI - Vertex indices of molecular graphs in structure-activity relationships: a study of the convulsant-anticonvulsant activity of barbiturates and the carcinogenicity of unsubstituted polycyclic aromatic hydrocarbons. PMID- 2312622 TI - Nail grafts for reconstruction. AB - Monkey digits were used experimentally to demonstrate the pathologic anatomy of nail deformities and the results of treatment using full and partial thickness nail matrix grafts. Seventy-five human nail deformities were evaluated and treated. In both the experimental and clinical groups, microscopic hypertrophy of the superficial epithelial elements underlying the deformed nail existed. A follow-up of treatment of nail deformities indicated that nail matrix grafts, both full and partial thickness, are beneficial when the defect involves the sterile matrix and the proximal nail fold. PMID- 2312624 TI - Use of vector processing to search the Cambridge Structural Database. AB - The Cambridge Structural Database (CSD) is a vast numerical resource of crystallographic data. The January 1989 release contains over 70,000 entries, and the data acquisition rate currently increases about 15% per annum. To be able to provide adequate response times for interactive data retrieval, using the new (1988) CSD file format, a vectorized search procedure has been developed as a modification of the CSD program QUEST. This procedure employs the pipelined vector facilities of the CONVEX C120 system to perform bitscreen logic, resulting in response times for arbitrary queries in the order of seconds, almost independent of the size of the database. PMID- 2312625 TI - [Long-term results of mastectomy in surgically treatble cancers at the Institut Curie from 1960 to 1973]. AB - Mastectomy remains the treatment of reference for breast cancer. Pre or post operative radiotherapy was the only adjuvant therapy possible for many years. This series of 2166 cases, treated between 1960 and 1973, analyses the survival, loco-regional recurrence rate, metastases and complications as a function of initial UICC staging and the type of treatment chosen. With follow up periods ranging from 15 to 25 years, we have shown that the clinical course is marked by recurrences for metastases occurring principally between the 2nd and 5th year, and that the number of events occurring beyond 10 years is still considerable. This study justifies the long term surveillance of patients. The results of current therapies need to be assessed in relation to historical data with a sufficiently long follow up, in order to confirm their efficacy. PMID- 2312626 TI - [Emergency vascular access in patients with renal failure. Apropos of 32 implantations of permcath]. AB - Central venous catheters allow for the most rapid hemodialysis procedure with sparing of peripheral blood vessels. 32 flexible, double-lumen "permcath" catheters were implanted to 27 patients over a period spanning 42 months (February 86-August 89). Catheter placement was definitive in 2 cases while another 30 provided previsory intravenous access for plasmapheresis (25 cases), acute renal insufficiency (7 cases), and chronic renal failure (17 cases). The mean utilization time per patient was 10.7 +/- 8.01 (SE) weeks. As respects chronic renal failure, this provided a time-opportunity for prospective maturation of conventional venous routes of access or transplantation. Permcath thrombosis occurred in 6 instances (18.75%), 5 times unremittingly (15.4%). Infection occurred in 6 patients (18.75%), leading to ablation of the permcath only once. Thus, permcath ensures safe, effective access for hemodialysis and enables maturation of a conventional venous cutdown. It may be used directly as a permanent vascular approach in case of limited life expectancy or of an extremely precarious vascular bed. PMID- 2312628 TI - [150 hepatic resections of malignant tumors. Technical aspects]. AB - One hundred and fifty hepatic resections for liver tumors have been performed in 130 patients during the last six years. The origin of the tumors was miscellaneous, but 76 resections were made for liver metastases from colo-rectal cancers, and all the types of hepatic resections were performed. The post operative mortality and morbidity were respectively 2% and 26%. After such an experience, we think that hepatic resections for tumors are currently safe surgical operations. This security comes from two technical ameliorations: the practice of intraoperative ultrasonography and the systematic use of repetitive pedicular clampings. A detailed account is done about the different operative technics concerning intraoperative ultrasonography, pedicle clamping and different types of systematized or atypical hepatectomies. PMID- 2312627 TI - [Intrathoracic goiter. Apropos of 36 cases]. AB - This article is concerned with 36 cases of plunging goiters responding to Eschapasse and Merlier definition. The frequency of plunging goiters is 5.2%, women are predominating with 96% and the average of age is 45 years. In 34%, these goiters gave rise to fow symptoms, while there was mediastinal complication in the others cases. Paraclinic investigations are limited to a face and profile pulmonary roentgenographies, and scintigraphy of the thyroid. In the treatment, cervicotomy proved to the completely satisfactory to removal of all the goiters and there were no need to sternotomy or thoracotomy. The pathology revealed two malignant tumors. Post operative evolution was uneventful except one death in the 10th post operative day by pulmonary emboli. PMID- 2312629 TI - [Esophageal metastases from cancer of the breast. Apropos of a case]. PMID- 2312630 TI - [Hepatic tuberculosis with a pseudotumoral form, apropos of 2 cases]. PMID- 2312631 TI - [Contribution of endoscopy in digestive non-Hodgkin's malignant lymphoma]. PMID- 2312632 TI - [Isolated tuberculosis of the appendix. Apropos of a case]. PMID- 2312633 TI - [Risk to the parathyroid glands in surgery of the thyroid]. AB - From 1981 to 1987, 305 patients underwent surgery in this department for thyroid disorders, including 7 reinterventions for total thyroidectomy, with a mortality of 0.75% and a specific morbidity of 13.4%. The overall incidence of post operative parathyroid insufficiency was 4.6%. This was higher after bilateral thyroidectomy (7.6%) than after unilateral thyroidectomy (0.7%). The early parathyroid risk was also higher after surgery for hyperthyroidism (9.7%) than after surgery for euthyroid goitres (2.4%). The true incidence of post-operative parathyroid insufficiency can only be evaluated by systematic clinical and biological investigation. Parathyroid insufficiency is due to devascularisation of one or several parathyroids during the course of thyroidectomy, or occasionally due to accidental resection with the thyroid lobe. The prevention of post-operative parathyroid insufficiency requires a surgical technique which limits any devascularisation of the parathyroid glands and if the vascular supply to a parathyroid is put at risk then autotransplantation should be performed. PMID- 2312634 TI - Linguistic significance of babbling: evidence from a tracheostomized infant. AB - The role of babbling in language development is not well understood. One source of evidence is the utterances of infants who were tracheostomized during the period in which they would normally have produced syllabic vocalization. We describe here the phonetic patterns and linguistic development of a girl called Jenny. She was tracheostomized and generally aphonic from 0.5-1.8 but cognitively and socially normal, with near-normal comprehension of language. Acoustic analyses of Jenny's utterances following decannulation revealed a tenth of the canonical syllables which might be expected in normally developing infants, an extremely small inventory of consonant-like segments, and a marked preference for labial obstruents. In these ways, she resembled a group of infants of the same age who also cannot hear their oral-motor movements, the congenitally deaf, suggesting that the audibility of babbling contributes to its onset. Two months following decannulation, when Jenny was 1.10, she produced only a handful of different words. We think this is because aphonia prevented her from discovering the referential value of vocal expression and discouraged the formation of a phonetic repertoire that could be appropriated for lexical service. This unusual case suggests that babbling normally facilitates the development of language and speech. PMID- 2312635 TI - Structure and function of baby talk in a day-care centre. AB - The aim of this study is to examine how caretakers speak to young children in a day-care centre and particularly to investigate how they adjust their language, according to children's age and to size of groups. Five Italian teachers were observed, each one during six different sessions. Children's ages were 0; 10-1; 2 and 2; 6-3; 0. The number of children varied from a rather large group (seven children) to a small group (three children) to a single child. Language was taperecorded during free-play sessions of ten minutes. Context was noted by two observers. Transcripts were analysed according to structural features (syntactical complexity, redundancy, type-token ratio, speed) and functional features (proportion of utterances with different purpose: control and organization of child behaviour, empathy, conversation and teaching). Results show some significant differences in structure and function according to children's age and group size. PMID- 2312636 TI - Young children's conversations with their mothers and fathers: differences in breakdown and repair. AB - In this study we compared the conversations of mothers and fathers with their children at 1; 3 and 1; 9, with special attention to breakdown-repair sequences. We found that, overall, children and secondary caregiver fathers experienced more communicative breakdowns than did children and primary caregiver mothers. More specifically, fathers requested clarification of their children more often than did mothers, and they most often used a non-specific query (e.g. What?). Mothers used more specific queries (e.g. Put it where?) and were involved in more 'looped' sequences involving multiple requests for clarification. Fathers also failed to acknowledge child utterances more often than did mothers. After a father non-acknowledgement, children tended not to persist and when they did they often received further non-acknowledgements; the dyad did not often return to the child's original topic. After a maternal non-acknowledgement, on the other hand, children persisted and the dyad more often returned to its previous topic. The results are interpreted as support for the Bridge Hypothesis which claims that fathers present children with communicative challenges that help prepare them for communication with less familiar adults. PMID- 2312637 TI - Conversational or communicative skill? A reassessment of two-year-olds' behaviour in miscommunication episodes. AB - Young children's competence in using and responding to clarification requests may reflect their desire to achieve goals through the direction of others rather than knowledge that messages must be understood by another mind. This possibility was addressed by examining miscommunication episodes between children aged 2; 6 and their parents in videotaped free play sessions. Although the children generally responded appropriately in form to parental clarification requests, they responded more often to and resolved successfully more of those following their own requests than those following their assertions. Thus, the results support the idea that young children are frequently motivated to repair their utterances when they have not achieved some overt behaviour desired from others. These findings are discussed in the light of the conversational experience two-year-olds bring to clarification situations. PMID- 2312638 TI - Second-language acquisition via immersion in daycare. AB - This paper presents a case study of second-language acquisition of Hebrew via immersion in daycare between 1.10 and 3.0. A period of silence was followed by rapid onset of L2 production simultaneously with many references to language itself. Eight types of language awareness were identified, and of these, several types may be prerequisites for starting L2 production. The nature of L2 speech during the first stages of production suggests that to crack the sematic code of L2, the child relies on identifiable contingencies between utterances and subsequent behaviours by speakers and listeners. As a result there are many more imperatives and interrogatives in L2 than are evident in L1 speech, and these appear to be learned by rote in an unanalysed manner. The transition to complex constructions occurs via the juxtaposition of known but syntactically unanalysed chunks, and results in patterns of syntactic errors similar to those of adult second-language learners. Reliance on L1 as a fall-back strategy was also evident. Several implications of these data for cognitive development in general are discussed. PMID- 2312639 TI - The acquisition of Irish: a study of word order development. AB - This study examines the development of word order patterns in Irish, a strict VSO language. It was found that the three children studied used subject-initial utterances considerably more frequently than adults in input, and that in both adult and child the elision of the verb 'to be' played a significant role. Another significant factor was found to be the different restrictions on main verbs and verbal nouns with regard to the subject: in neutral sentences the main verb always precedes the subject, while the verbal noun always follows it. The Bates & MacWhinney (1979) hypothesis that early verb initialization results from a tendency to place new information before given information was also investigated. PMID- 2312640 TI - Early lexical acquisition: rate, content, and the vocabulary spurt. AB - The transition from slow to rapid word-learning was examined in a longitudinal study of 18 children. Beginning at age 1.2, mothers kept a diary of children's words. Diary entries were discussed during phone calls to the home every 2 1/2 weeks. A chronological record of nouns and other word classes was coded from the diary records. Thirteen children evidenced a prolonged period of up to three months during which rate of acquisition markedly increased. Almost three-quarters of the words learned during this period were nouns. Five children evidenced more gradual word-learning, and acquired a balance of nouns and other word classes. These results suggest that the terms 'vocabulary spurt' and 'naming explosion' best describe children who focus their early linguistic efforts on a single strategy: learning names for things. Other children may attempt to encode a broad range of experience with a more varied lexicon, a strategy that results in more gradual lexical growth. PMID- 2312641 TI - The comprehension of metaphor by preschool children. AB - Comprehension of metaphor in preschoolers was studied through an elicited repetition task. Subjects were 52 children aged 3.0 to 5.2. Repetition performance on metaphors was compared to repetitions of semantically well-formed literal sentences as well as semantically anomalous sentences, all matched for length, vocabulary and sentence structure. Accuracy on literal and metaphoric stimuli was comparable, and both were significantly better than performance on anomalous sentences. There were no effects for age or sex. It was shown that the metaphors were not semantically anomalous to the children and that they were processed on a par with literal language. The argument is advanced from a review of the literature that imitation implicates understanding of the material imitated. If metaphor is thus shown to emerge early in the child's linguistic repertory, figurative language, it may be argued, occupies a more central position in linguistic theory than it has been accorded. PMID- 2312643 TI - Children's understanding of adverbs denoting degree of likelihood. AB - Two studies were conducted to examine children's understanding of three terms that denote different degrees of likelihood: possibly, probably and definitely. In Study I, children in preschool, and first, third and fourth grade completed a comparison task involving pairs of likelihood terms. Twelve stories were created that described the likelihood that each of two children would participate in an activity, and subjects judged which of the two children actually participated. In Study 2, children in preschool, and first, third and fifth grade evaluated separate statements describing three different children, each of whom was said to have a different estimate of the likelihood that a scary event depicted in a movie would actually occur. Subjects rated how scared each of the three children felt. The results of the two studies revealed that preschoolers showed very little comprehension of the meaning of any of the three words, but by fourth grade the majority of children distinguished among all three terms. Children understood the distinction between definitely and both of the other terms (possibly, probably) better than they understood the distinction between possibly and probably. This finding is consistent with research on the development of children's understanding of probability concepts. Unexpectedly, the distinction between probably and definitely seems to emerge at a younger age than the distinction between possibly and definitely. The findings are discussed in terms of their implications for communicating verbal messages to children. PMID- 2312642 TI - Similarity neighbourhoods of words in young children's lexicons. AB - Similarity neighbourhoods for words in young children's lexicons were investigated using three computerized databases. These databases were representative of three groups of native English speakers: 5-year-olds, 7-year olds, and adults. Computations relating to the similarity neighbourhoods of words in the children's and adult's lexicon revealed that words in the 5- and 7-year olds' lexicons have many fewer similar neighbours than the same words analyzed in the adult lexicon. Thus, young children may employ more global recognition strategies because words are more discriminable in memory. The neighbourhood analyses provide a number of insights into the processes of auditory word recognition in children and the possible structural organization of words in the young child's mental lexicon. PMID- 2312644 TI - On the confirmation of bioprograms. PMID- 2312645 TI - Locative terms and Warlpiri acquisition. AB - Cognitive complexity and complexity of linguistic structure have been found to influence the order of acquisition of locatives. In Warlpiri, locative terms are nominals and they are used in combination with a locative case marker on the reference object; directional affixes may be added to them. Data from a series of tests of Warlpiri children's comprehension and production of the Warlpiri expressions that may be translated as 'in', 'on', 'under', 'in front of', 'behind' and 'between' indicate that the locative case forms are used first without the more specific locative nominals; young children distinguish an 'up down' dimension but not 'in', and the reference object influences how the locative term is interpreted; kamparru-pirdangirli ('front-behind') is not one dimension for children aged four to five years; kulkurru 'between' is understood before kamparru 'front' and pirdangirli 'behind'; the use of features on a reference object for orientation develops at around six, but the orientation of the reference object, as well as features on the placed object may affect interpretation. PMID- 2312646 TI - Subject, topic and Sesotho passive. AB - Counter to findings in English, German and Hebrew, recent acquisition studies have shown that the passive is acquired early in several non-Indo-European languages. In an attempt to explain this phenomenon, this paper addresses certain typological phenomena which influence the early acquisition of passives in Sesotho, a southern Bantu language. After outlining the structure of the Sesotho passive and its syntactic and discourse functions, I examine Sesotho-speaking children's spontaneous use of passives, showing that the acquisition of passives in Sesotho is closely linked to the fact that Sesotho subjects must be discourse topics. I conclude that a detailed examination of how passive constructions interact with other components of a given linguistic system is critical for developing a coherent and universally applicable theory of how passives are acquired. PMID- 2312648 TI - Annual research review. PMID- 2312647 TI - Maternal speech and the child's development of syntax: a further look. AB - The present study compared four categories of maternal utterances that were found in a previous study (Hoff-Ginsberg, 1986) to predict children's rates of syntax development to a category of maternal utterances that was unrelated to syntax development. The comparisons were designed to test the hypotheses that maternal utterances which benefit syntax development do so by providing syntactically rich data or by eliciting conversation from the child. Data-providing and conversation eliciting characteristics of the selected categories of maternal utterances were assessed from the same transcripts of 22 mothers interacting with their 2 1/2 year-old children that had provided the database for the earlier study of predictive relations. Each of the three positive predictor categories of maternal utterances differed from the unrelated category--in more frequently illustrating the affected aspect of syntax development, in eliciting more speech from the child, or both. Neither of these characteristics was true of the negative predictor category. The pattern of results suggested that maternal speech supports the child's development of syntax by engaging the child in linguistic interaction and also by providing illustrations of the structures the child acquires. PMID- 2312649 TI - The recognition failure and graphic success of idiot-savant artists. AB - Three groups of subjects, an idiot-savant group, a group of mentally handicapped subjects matched for IQ, and normal artistically gifted children, were compared for their recognition and graphic reproduction abilities. It was found that, independent of input modality, level of intelligence determined recognition performance, while graphic ability independent of IQ was the determining factor in reproduction accuracy. PMID- 2312650 TI - Art and accuracy: the drawing ability of idiot-savants. AB - The accuracy and the artistic merit of drawings produced by graphically gifted idiot-savants and by artistically able normal children were investigated in various conditions. Drawings had to be executed when a three- or two-dimensional model of the scene to be drawn was in view, or when it had to be remembered or drawn from another viewpoint. It was found that overall accuracy was better for the normal than for the mentally handicapped subjects. In contrast, ratings for artistic merit did not differentiate the groups. It is concluded that while the accuracy of drawings may be related to intelligence, the artistic quality of the graphic production is not. PMID- 2312651 TI - Classification of abnormal psychosocial situations: preliminary report of a revision of a WHO scheme. AB - A WHO working group undertook a radical revision of the psychosocial axis for the classification of abnormal psychosocial situations. The rationale for the revision and the approach taken is described, together with the overall structure of the coding scheme and the subcodings within each category. PMID- 2312652 TI - Epidemiology and course of psychiatric disorders in school-age children--results of a longitudinal study. AB - In an epidemiological longitudinal study, 356 out of 399 8-yr old children were re-examined at age 13. Prevalence rates for psychiatric disorders of about 16% remained constant during adolescence. The course of emotional disorders proved very promising, while that of conduct disorders was extremely unfavorable. Remission of psychiatric disorders was also influenced by an improved psychosocial environment within the family. Development of disorders in initially healthy children was related to prior learning disabilities and stressful life events. More effective approaches in the treatment of conduct disorders as well as early detection of detrimental familial conditions and learning disabilities are called for. PMID- 2312653 TI - Problems and competencies reported by parents of Australian and American children. AB - We compared problems and competencies reported for 2600 randomly selected nonreferred children in Sydney and the U.S.A. Sydney children scored significantly higher on 82 problem items, with a mean total problem score of 31.6 versus 20.1 for the U.S.A. Nevertheless, item scores correlated 0.92 between countries, most differences between competence scores were small, and patterns were similar for sex, age, socioeconomic status, and internalizing versus externalizing problems. Although higher clinical cutoffs may be needed in Sydney, the similarity of patterns in scores permits calibration of the Child Behavior Checklist between Sydney and the U.S.A. Sex differences found in seven cultures were summarized. PMID- 2312654 TI - The clinical significance of neurocognitive impairments among children with psychiatric disorders: diagnosis and situational specificity. AB - The overall objective of this paper is to assess the clinical significance of neurocognitive impairments (NCI) among children with psychiatric disorders. One hundred and fifty-three children referred to a mental health clinic underwent neuropsychological testing. Their parents were interviewed to obtain background information and data on their children's behavior. Parents and teachers also filled out behavior checklists. The results suggest that neurocognitive impairments are: (1) more strongly associated with externalizing rather than internalizing psychiatric diagnoses; and (2) are correlated with psychiatric symptoms at school, but not at home. The implications for understanding the impact of neurocognitive impairments on the situational specificity of psychiatric symptoms are discussed. PMID- 2312655 TI - A special link between rhyming skill and the use of orthographic analogies by beginning readers. AB - The existence of a strong correlation between phonological awareness and the development of reading has long been known. More recently, it has been shown that pre-reading rhyming skills are the best predictor of later reading ability that we have. One reason for this relationship may be that children who have put words into rhyming categories before they begin school may be quick to realize that these words also tend to share the same spelling patterns, and may then use such similarities in spelling to make predictions (analogies) about how new written words will sound. The present study tests one aspect of this hypothesis, which is that children who make more analogies in reading are also better at rhyming than children who do not. Evidence consistent with this prediction is presented. PMID- 2312656 TI - Unit-based nursing quality assurance. PMID- 2312657 TI - Use of nursing process to develop unit specific quality assurance plans. PMID- 2312658 TI - Developing a unit-based quality assurance tool. AB - Due to the dynamic nature of QA, the indicators for the critical care nursing division will continue to change in response to societal, professional, and individual values, as well as to advances in scientific knowledge. Perhaps the latter will present the greatest challenge to the CNS, whose direct and indirect roles influence the quality of care in the critical care setting. PMID- 2312659 TI - Motivating and sustaining commitment to quality assurance. AB - It is important to realize the dynamics of individual as well as group motivation when planning QA activities because measuring the quality of care should be important to all staff on the unit. The nursing manager, however, is a crucial individual to involve in QA activities in order to make unit QA activities a priority for the unit. By understanding the dynamics of motivation and change, the QA coordinator can successfully work with nursing managers and nursing staff to demonstrate the impact of QA activities on enhanced quality of care. PMID- 2312660 TI - Correlation of nurses' knowledge and valuation of the quality assurance process. AB - Nurses are expected to use the QA process as a means of improving the quality of patient care and as a means of professional accountability. The responsibility for preparing nurses to meet this expectation falls first on nurse educators and then on nurse administrators. If a positive relationship had been found between nurses' knowledge of and valuation of the QA process, nurse educators and administrators could have used the relationship in curriculum development and in continuing education planning for students and nurses. By including QA theory and process in nursing curricula, beginning with early nursing education and continuing through educational inservice sessions in the workplace, nurses would be more likely to internalize the concepts of QA. With earlier and continued exposure to the concepts of QA, nurses should gain both knowledge and valuation of the process and would subsequently be better prepared to use the QA process. Since participation in QA activities has been identified as a required function in nursing, there is a need in nursing education and practice for the development of QA programs that attract the attention and participation of staff nurses. To facilitate the development of such programs, the variables that influence nurses' use of the QA process must be identified. As long as the profession of nursing and the regulating bodies over nursing require accountability for professional services and the improvement of patient care in the form of QA programs, nurses' use of the QA process will be of major importance. Some research suggests that implicit or explicit norms of accountability or responsibility regulate individual conduct, rather than personal valuation of the activity. This proposition could be the focus of future studies in nursing QA. Previous studies point to the fact that increased knowledge of a subject or phenomenon is positively related to personal valuation and activity related to the subject or phenomenon. Although this relationship was not found in this study, identification of factors that contribute to an increased valuation of or participation in nursing QA activities should continue to be the subject of nursing research. PMID- 2312661 TI - Role development: the nursing quality assurance coordinator. AB - This application of the Benner Model to the role experiences of the NQA coordinator demonstrates the usefulness of this framework to describe the progressive development of the role. In Benner's model, there are three distinct areas for discussion. First, as the nurse moves from the expert role of staff nurse or head nurse to the role of novice NQA coordinator, many very real situations are encountered that have the potential to create frustrations and adverse feelings within the nurse. It is equally important for the position holder, as well as the supervisor, to recognize these as the normal growth stage of the novice, so that appropriate actions can be taken to positively help the NQA coordinator through these early developmental stages. Secondly, initial acceptance of the NQA coordinator role creates feelings of anticipation, challenge, and excitement. However, in spite of this, the novice is soon likely to feel threatened and alone. This feeling is related to various situations, such as the lack of formal guidance and role preparation. As a result, the novice NQA coordinator often needs to accept the responsibility for self-direction in role preparation. At this point, it may be quite overwhelming for the NQA coordinator to take personal responsibility for obtaining the knowledge and skills necessary to be successful in the role. To be successful, it is vital for the novice and advanced beginner to identify developmental needs and to obtain the resources and support needed during these crucial stages. Finally, the personal reflection on the experiences of two NQA coordinators demonstrates that, although the developmental stages are relatively well defined, they may not always be clear cut, and there may be vacillation between stages. These are normal phenomena for which strategies can be identified to enhance adaptation and growth within the particular stages of skill acquisition. The proposed time frames noted for each stage of role development may be somewhat arbitrary. Many variables, such as degree of specialization, urgency of the task, and characteristics of the position holder, organization, and health care environment will influence role development. Thus, the individual may not experience a straightforward and clear cut progression but rather a back-and-forth movement through the various stages. The role experiences of the NQA coordinator are easily conceptualized using the Benner framework.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2312662 TI - The development of an evaluation tool for unit-based quality assurance. AB - A great deal of time, research, and effort was expended in converting the LRMC nursing division from a centralized plan to a decentralized focus. Inherent in the process was the belief that unit-based QA programs offer an excellent opportunity for change, empowering the staff nurse to act as the change agent in improving patient care and enhancing nursing practice. A necessary component in the QA process is evaluation, enabling nurses to step back from the "busyness" of a unit-based committee to identify documented improvements in patient care and to provide validation for changes in nursing practice. The process of evaluation allows nurses the means to appraise the worth and merit of their unit-based QA program. For all levels of nursing, time is a scarce commodity. The realities of the nursing shortage dictate that all programs with staff nurse involvement be examined carefully. For these reasons, thorough and meaningful annual appraisal is critical to ensure that the time spent in implementing and maintaining a unit based QA program is worth the effort. PMID- 2312663 TI - Implementing a unit-based quality assurance program. AB - QA yields opportunities to improve patient outcomes as well as to identify problem areas. QA activities work when they are planned, systematic, organized, and ongoing. Monitoring is most easily completed concurrently by staff as part of their everyday activities rather than as an extra task to be done after a regular shift. Since staff nurses are the primary caregivers in this institution, a unit based model for QA, where staff take the responsibility, yielded the best overall improvements in patient outcomes and quality of care. PMID- 2312664 TI - Establishing and monitoring an endemic medication error rate. PMID- 2312665 TI - A standardized data collection tool. AB - To successfully integrate data collection into the staff's responsibilities, the process must be simple, concise, and easy to use. The data collection tool described in this article includes all the important information at a glance, permits easy comparison with projected and actual thresholds, and analysis of data with follow-up action. It reduces the volumes of paperwork required in many systems. Since the indicators are written on only one paper, there is a reduction in transcription time. Additionally, one paper that contains a sample of twenty should be adequate for a unit-based indicator. Use of this tool reduces the number of papers that must be handled by the QA coordinator as well. Finally, the tool is flexible enough to use in a variety of settings. PMID- 2312666 TI - Introducing new forms: overcoming resistance. AB - Implementing newly created or revised forms is often difficult and time consuming, and resistance is possible at any stage in the process. However, resistance forces clarity of purpose and dedication. A deliberately planned and carefully managed change process can achieve the goals of the task force and Nursing Administration. The QA nurse analyst is in a strategic position to facilitate this process and achieve a successful outcome within a specific period of time. By involving the head nurses in the initial developmental stage and receiving input from the staff nurses throughout, resistance at the implementation stage will be minimized. Experience with form development illustrates the principle that people affirm change when they have been actively involved in the development process. PMID- 2312667 TI - Effects of recombinant leukocyte interferon on serum immunoglobulin concentrations and lymphocyte subpopulations in chronic hepatitis B. AB - To investigate immune effects of interferon (IFN) therapy in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, serum immunoglobulin concentrations and peripheral lymphocyte subpopulations were sequentially studied before, during, and after therapy in nine patients who were treated with recombinant human alpha-IFN in doses ranging from 3 to 10 million units per day for 28 days. Serum immunoglobulin A levels decreased significantly, from 414 +/- 23 mg/dl (mean +/- SE) to 379 +/- 28 mg/dl (P less than 0.05), after the first week of therapy and to a bottom value of 323 +/- 20 mg/dl (P less than 0.001) at the fourth week. Immunoglobulin G levels decreased significantly, from 2603 +/- 175 to 2328 +/- 169 mg/dl (P less than 0.005), after the first week of therapy and to a bottom value of 2005 +/- 199 mg/dl (P less than 0.001) at the fourth week. Immunoglobulin M levels were also reduced significantly after 3 weeks of therapy (from 229 +/- 23 to 188 +/- 15 mg/dl; P less than 0.01). These reductions in immunoglobulins A, G, and M returned to pretreatment levels by 4 months after the end of the therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312668 TI - Natural killer cell-mediated lysis of Mycobacterium-avium complex-infected monocytes. AB - Since the precise mechanism of host responses to infection with Mycobacterium avium complex (MAC) is unclear and since cytotoxic lymphocytes may be involved in the destruction of cells infected with intracellular pathogens, we investigated the ability of normal peripheral blood lymphocytes to kill MAC-infected monocytes in a short-term isotope release assay. Nylon wool-passed lymphocytes lysed MAC infected but not uninfected monocytes during a 4-hr assay. Infected monocytes were less sensitive to cell-mediated killing than the standard natural killer (NK) cell-sensitive cell line K562, although the kinetics of lysis were similar. The release of lymphocyte-derived mediators such as tumor necrosis factor, interleukin-2 (IL-2), and interferon-alpha and -gamma could not be implicated as a cause of monocyte death. Through the use of cell-specific monoclonal antibodies plus complement, the phenotype of the effector cell was that of an NK cell (CD3 negative, partially CD8 negative, and CD16 positive). The use of highly purified, negatively selected NK cells confirmed these results. NK cell-mediated lysis of infected monocytes decreased MAC viability, indicating that this cytotoxic activity would not favor dissemination of the organism. The killing of MAC infected monocytes was reduced by K562 cells, suggesting that these targets shared common recognition/binding structures. These results suggest that NK-cell function may be important in the prevention of or response to MAC infection and may help explain the predilection of AIDS patients to develop widespread disease. PMID- 2312669 TI - Comparison of the staphylocoagulase activities of Staphylococcus aureus and Staphylococcus intermedius on Chromozym-TH. AB - The staphylocoagulases of Staphylococcus intermedius (39 strains from clinical samples from dogs and 1 strain from a pigeon) and Staphylococcus aureus (40 strains from nine different animal species) were compared by using the chromogenic methods of Engels et al. (W. Engels, M. Kemps, and C. P. A. van Boven, J. Clin. Microbiol. 14:496-500, 1981). S. intermedius produced staphylocoagulase which resembled that of S. aureus in its rate and method of action on prothrombin, but S. intermedius produced it in lesser amounts. Therefore, chromogenic substrate tests such as Chromozym-TH (Boehringer GmbH, Mannheim, Federal Republic of Germany) (as described by Engels et al.) can be used for the detection of staphylocoagulase in both of these species. However, to detect accurately the presence of S. intermedius staphylocoagulase by this method, preconcentration of the extracellular proteins or an extension of the reaction time of the test would be required. The method described by Engels et al. was designed specifically for clinical laboratories that handle human samples. Under those circumstances the method could be regarded as specific, enabling an identification of S. aureus only. However, as both S. aureus and S. intermedius give positive results in this test, in veterinary diagnostic laboratories, heavy reliance must not be placed on this test for determination of organisms to the species level. PMID- 2312670 TI - Evaluation of three Chlamydia trachomatis immunoassays with an unbiased, noninvasive clinical sample. AB - First-catch early morning urine samples from patients attending a genitourinary medicine clinic were tested by three different enzyme immunoassays. The results suggest significant differences in the sensitivities and specificities of the different assays. The direct visualization of elementary bodies in urine deposits by direct immunofluorescence was used as the "gold standard," using a monoclonal antibody with a different epitope specificity from those of antibodies used in the enzyme-linked immunosorbent assays. We report for the first time that urine specimens represent an unbiased sample, free of the inherent sampling errors associated with other genital specimens. We feel that urine is a valid specimen for use in any evaluation study of new assays directed towards the detection of Chlamydia trachomatis. PMID- 2312671 TI - Hemolysin patterns of Actinobacillus pleuropneumoniae. AB - The secreted hemolytic activities produced by the reference strains and field isolates of the 12 serotypes and 2 subtypes of Actinobacillus pleuropneumoniae were analyzed. Serotype 1 produced a Ca2(+)-inducible hemolysin, which was previously characterized as a 105-kilodalton protein and was named hemolysin I (HlyI). Serotypes 2, 4, 6, 7, and 8 produced a different hemolytic activity that was not inducible by Ca2+ but required this ion for its activity. The hemolytic activity produced by these serotypes was much weaker than that found in serotype 1 and was not neutralized by rabbit antibodies against HlyI. It was, however, neutralized by serum from pigs that were experimentally infected with a serotype 2 strain and was called hemolysin II (HlyII). Serotypes 5a, 5b, 9, 10, and 11 produced both HlyI and HlyII. In these strains, HlyI was the major contributor to the hemolytic activity. The remaining serotypes, 3 and 12, produced a very weak hemolytic activity, which was not further analyzed. Immunoblot analysis of the culture supernatants from all 12 serotypes with rabbit polyclonal antibodies directed against HlyI revealed reactions with a protein in the 105-kilodalton size range for all serotypes, indicating that HlyI and HlyII might be serologically related. Strains producing active HlyI seem to belong to serotypes that are generally considered to be virulent types and that are frequently isolated from pigs in severe pleuropneumonia outbreaks. PMID- 2312672 TI - Antigenic variation of Giardia lamblia in the feces of Mongolian gerbils. AB - Enzyme-linked immunoelectrotransfer blot was used to study variations in Giardia lamblia antigens in extracts of feces from infected Mongolian gerbils. A 65 kilodalton antigen was found in feces that contained strain WB (ATCC 30957) cysts and in axenic culture of strains WB and CDC:0284:1 that contained trophozoites. The 65-kilodalton antigen from trophozoites of both strains was membrane associated. A 70-kilodalton antigen was found in feces that contained strain CDC:0284:1 cysts. It was persistent in 16 fecal collections and may be strain specific. Similar variations in antigens may occur in human feces. Coproimmunodiagnostic assays that use monoclonal antibodies will have to include all varieties of G. lamblia antigens present in the feces of giardiasis patients. PMID- 2312673 TI - Biochemical identification of Aeromonas genospecies isolated from humans. AB - One hundred phenotypic characteristics were determined for 138 clinical and environmental Aeromonas strains. Cluster analysis revealed three major phenons equivalent to the A. hydrophila, A. caviae, and A. sobria groups, each of which contained more than one genospecies and more than one named species. An excellent correlation was found between phenotypic identification and classification based on DNA relatedness. DNA hybridization groups within each of the phenotypic groups were also separable by using a few biochemical characteristics. Key tests were production of acid from or growth on D-sorbitol (which separated DNA hybridization group 3 from groups 1 and 2 within the A. hydrophila phenogroup), growth on citrate (which essentially separated DNA hybridization group 4 from groups 5A and 5B within the A. caviae phenogroup), and growth on DL-lactate (which separated DNA hybridization group 1 from groups 2 and 3 within the A. hydrophila phenogroup as well as group 5A from groups 4 and 5B within the A. caviae phenogroup). All except one strain in the A. sobria phenogroup belonged to DNA hybridization group 8. DNA hybridization groups were not equally distributed among clinical and environmental isolates, suggesting that strains of certain DNA hybridization groups might be less virulent than others. PMID- 2312674 TI - Growth promotion of Bifidobacterium species by whey and casein fractions from human and bovine milk. AB - An in vitro assay was used to study the growth-promotional activity of human milk (HM), cow's milk (CM), and whey and casein fractions of HM and CM for five strains of Bifidobacterium species isolated originally from stools of human infants. Whey- and casein-predominant CM-based infant formulas were studied as well. When compared on an equivalent protein basis, the growth promotion activity of HM was greater than that of CM for Bifidobacterium bifidum serovar pennsylvanicus and Bifidobacterium longum but comparable for B. bifidum, Bifidobacterium infantis, and Bifidobacterium breve. Pasteurization of HM and CM resulted in an increase of growth promotion activity for B. bifidum serovar pennsylvanicus and B. bifidum, a decrease for B. infantis, and no change for B. longum and B. breve. The growth promotion activity of HM whey was slightly higher than that of HM casein for four strains of bifidobacteria. When CM casein was a substrate, virtually no growth occurred for B. bifidum serovar pennsylvanicus, B. bifidum, B. infantis, and B. longum. The growth promotion activity of CM whey, however, was similar to that of HM whey. A similar trend was observed for CM based infant formula. Whey-dominant formulas promoted better growth of B. bifidum serovar pennsylvanicus, B. bifidum, and B. infantis than casein-dominant formulas. The data suggest a direct relationship between amount of whey-specific factors and the ability to promote growth of clinically relevant strains of Bifidobacterium species by HM, CM, and CM-based infant formulas. PMID- 2312675 TI - Detection of serotype-specific antibodies or capsular antigen of Actinobacillus pleuropneumoniae by a double-label radioimmunoassay. AB - Diagnostic tests for Actinobacillus pleuropneumoniae have been problematic because current tests do not use a purified antigen and in most cases measure either antibody or antigen, but not both. We describe a Farr-type double-label radioimmunoassay that utilizes purified, serotype-specific, 3H-capsule to measure antibody to capsule directly or that can measure capsule in a sample indirectly by inhibition of antibody binding. The assay could detect about 1 ng of serotype specific antibody in serum or at least 100 pg of capsule in a sample. Due to the sensitivity of the assay, false-positive results were common with neat sera (probably due to cross-reacting antibodies to unrelated antigens), but the specificity was improved when the sera were diluted 1:100. The radioimmunoassay should prove to be a useful reference method for research and diagnostic testing and for comparison of new assays for detection of capsule or antibodies to capsule. PMID- 2312676 TI - Species-specific oligodeoxynucleotide probes for the identification of periodontal bacteria. AB - Oligodeoxynucleotide probes were developed for identification of the periodontal bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, B. intermedius types I and II, B. forsythus, Eikenella corrodens, Fusobacterium nucleatum, Haemophilus aphrophilus, Streptococcus intermedius, and Wolinella recta. Probes were designed by sequencing the 16S rRNA for each bacterium, identifying hypervariable regions, and chemically synthesizing species-specific probes. These probes were specific when tested against a panel of nucleic acids from closely related bacteria. PMID- 2312677 TI - Tuberculous anergic sera or purified protein derivative treatment induces modification in lymphocyte transformation of cells from patients with tuberculosis. AB - Peripheral blood mononuclear cells from 20 purified protein derivative (PPD) reactive (PPD+) tuberculous patients were cultured in autologous, tuberculous anergic, or normal serum. After 12 h of incubation, the serum was eliminated and lymphocyte transformation with PPD was performed. Transformation was inhibited only in cells incubated with anergic serum. In contrast, cells from 11 anergic tuberculous (PPD-) individuals recovered the ability to respond to an optimal PPD dose after treatment with high PPD concentrations followed by several washings. The cells which recovered returned to their initial anergic state when incubated with sera from anergic patients. Under both conditions, incubation with sera did not abolish the response to the mitogen phytohemagglutinin. Cells from healthy PPD+ or PPD- individuals were used as controls. The most important finding derived from serum analysis was the increased levels of specific immunoglobulins G and A in anergic patients. PMID- 2312678 TI - Pathogenicity factors and virulence for rainbow trout (Salmo gairdneri) of motile Aeromonas spp. isolated from a river. AB - Ninety-seven motile Aeromonas strains were isolated over a period of a year from samples of water and sediment collected at different sites along a river. Strains were regularly recovered from all samples, regardless of the source of isolation or seasonal conditions. Isolates were biochemically characterized by the API 20NE system (Analytab Products, Plainview, N.Y.) and classified as Aeromonas hydrophila (74 strains), Aeromonas sobria (11 strains), and Aeromonas caviae (12 strains). Despite the high level of homogeneity observed in their biochemical patterns, they displayed different degrees of virulence for fish; 72.02% of A. hydrophila isolates and 63% of A. sobria isolates were virulent for fish by intramuscular challenge, but lower frequencies of virulence were observed when intraperitoneal injections were used. All A. caviae strains proved to be avirulent. Caseinases, hemolysins, and Vero cytotoxins were produced by 100, 91, and 94.59%, respectively, of A. hydrophila strains and with lower frequencies and lower caseinase activities by A. sobria isolates. No correlation was found between these activities and the degree of virulence of the strains for fish. Most hydrophobic strains seem to be concentrated in A. caviae, A. sobria, and avirulent A. hydrophila groups. Known virulence markers commonly associated with virulent strains (acriflavine negative and self-pelleting negative and precipitation after boiling positive phenotypes) had a low representation in the total of strains studied and were not associated with virulence. PMID- 2312679 TI - Experimental cryptosporidiosis in hamsters. AB - A new laboratory animal model for experimental cryptosporidiosis is described. Adult immunosuppressed hamsters were infected per os with 0.5 x 10(5) and 1 x 10(5) Cryptosporidium oocysts of calf origin. The mean numbers of oocysts shed per gram of feces per day and the patterns of infection are described. The susceptibility to Cryptosporidium infection, the total number of oocysts shed (a thousand times the infective dose), and the ease of handling in laboratory conditions make hamsters a good animal model for cryptosporidiosis. PMID- 2312680 TI - Reactivity of coagulase-negative staphylococci isolated from cow and goat milk with monoclonal antibodies to Staphylococcus aureus capsular polysaccharide types 5 and 8. AB - Monoclonal antibodies to Staphylococcus aureus capsular polysaccharide types 5 and 8 were used in an enzyme-linked immunosorbent assay to serotype 74 and 42 coagulase-negative isolates from cow and goat milk, respectively. Eighteen (15.5%) isolates were typable: 13 Staphylococcus haemolyticus, 1 S. hyicus, 1 S. simulans, and 1 S. warneri from bovine origin and 2 S. lentus from caprine origin. Type 5 was predominant, accounting for about 89% of typable isolates. Reactivity with monoclonal antibodies varied considerably according to isolates. The significance and the potential importance of these findings are discussed. PMID- 2312681 TI - Isolation of salmonellae from dried rattlesnake preparations. AB - Salmonella arizonae and other Salmonella serovars were isolated from four different rattlesnake preparations which were used for self-treatment of various diseases. A case of disseminated S. arizonae infection is reported in a patient who had acquired immunodeficiency syndrome and ingested dried rattlesnake. PMID- 2312682 TI - Canine ehrlichiosis in Connecticut. AB - The first case of canine ehrlichiosis in Connecticut is reported. A female Brittany spaniel from Milford presented with lethargy, anorexia, fever, petechiae, splenomegaly, thrombocytopenia, anemia, elevated serum alkaline phosphatase, lymphopenia, and hypoalbuminemia. Serologic analysis revealed antibodies to Ehrlichia canis (titer, 1:2,560). This documents a more northern geographic distribution in the United States for this infectious agent than had previously been suspected. PMID- 2312683 TI - Routine in vitro cultivation of Giardia lamblia by using the string test. AB - In vitro axenic cultures of Giardia lamblia were successfully established in 14 successive subjects by a method employing the string test (Entero-Test) for obtaining samples of fluid from the proximal small intestine. This method is applicable to isolating G. lamblia from unselected subjects, including asymptomatic carriers, children, and individuals in diverse or remote geographic regions. PMID- 2312684 TI - Discordant results between the broth disk elution and broth microdilution susceptibility tests with Bacteroides fragilis group isolates. AB - Susceptibility testing of 161 clinical isolates of the Bacteroides fragilis group was performed to compare interpretive results generated by the broth disk elution and broth microdilution methods recommended by the National Committee for Clinical Laboratory Standards. Among the cephalosporin-cephamycin compounds tested, correlation was poorest for ceftizoxime (71%), ceftriaxone (57%), and cefotaxime (47%); when the tests did not correlate, false resistance was seen 92, 95, and 93% of the time, respectively. Cefotetan and cefoperazone showed lack of correlation in 19 and 20% of the tests, respectively. For cefotetan, false resistance was more frequent, while with cefoperazone, false susceptibility occurred more often. Cefoxitin produced the fewest discrepancies; 10% of the disk elution tests produced either false-resistance or false-susceptibility results. Mezlocillin and piperacillin showed lack of correlation in 8 and 14% of the tests, respectively, and discrepancies were due primarily to false-resistance results. Overall with the beta-lactams, 84% of the discordant interpretive results were false resistance by the broth disk elution test. Clindamycin had a discrepancy rate of 10%, with the majority of discrepancies being false susceptibility disk elution results. Because of the high number of discrepancies noted with ceftizoxime, ceftriaxone, and cefotaxime, we recommend that these drugs not be tested by the disk elution method and that they be tested by a quantitative MIC method such as the broth microdilution test. Furthermore, caution should be exercised when interpreting broth disk elution results with all the beta-lactams included in this study except imipenem. These data indicate the lack of correlation of results between these two tests for many beta-lactams and suggest the need for a reexamination of the disk elution method to provide a more accurately standardized test. PMID- 2312685 TI - Purification and amino-terminal sequence analysis of the complement-fixing and precipitin antigens from Coccidioides immitis. AB - Two proteins (21 and 48 kilodaltons) purified from endospore-spherule culture filtrates of Coccidioides immitis are identified as precipitin and complement fixing antigens, respectively. To allow specific structural comparison to antigens identified by other investigators and as a first step to eventual serodiagnostic antigen production by recombinant DNA technology, amino-terminal amino acid sequences were determined for these antigens. PMID- 2312686 TI - Reevaluation of the cellular fatty acid composition of Legionella micdadei Bari 2/158. AB - The cellular fatty acid composition of Legionella micdadei Bari 2/158 was reevaluated because of its purported differences from other L. micdadei strains and its similarity to L. bozemanii. We found the fatty acid content of this strain to be consistent with that of 11 other strains of L. micdadei, including the presence of an anteiso branched-chain, monounsaturated, 17-carbon acid (Ca17:1) which is characteristic of this species. The double-bond position of Ca17:1 was established at the omega 7 (or delta 9) position by combined gas chromatographic-mass spectrometric analysis of dimethyl disulfide derivatives. The Ca17:1 omega 7 acid was absent in each of 14 strains of L. bozemanii. PMID- 2312687 TI - Pyrazinamidase activity as a phenotypic marker for several Aeromonas spp. isolated from clinical specimens. AB - Negative pyrazinamidase activity was significantly associated with Aeromonas sobria, and positive pyrazinamidase activity was associated with A. hydrophila and A. caviae (chi 2, P less than 0.0001). The absence of pyrazinamidase activity may be a potentially significant phenotypic marker for A. sobria. PMID- 2312689 TI - Evaluation of the rapid Patho Dx Latex Strep Grouping Kit. AB - A variety of clinical specimens from throat, nose, ear, eye, wounds, urine, and vagina were collected, cultured, and screened for beta-hemolytic streptococci. The Patho Dx Latex Strep Grouping Kit (Diagnostic Product Corp., Los Angeles, Calif.) technique was applied to colonies taken right from the primary cultures. Isolated strains were sent to the reference laboratory where they were grouped by standard techniques. The kappa coefficient of agreement between the Patho Dx Kit and the standard method was 0.958. We believe that, although better agreement was achieved by others with isolated colonies, a very good agreement is also achieved with primary cultures. The fact that the laboratory is able to report an accurate answer after only 24 h seems most advantageous. PMID- 2312688 TI - Isoprenoid quinones of Campylobacter cryaerophila, C. cinaedi, C. fennelliae, C. hyointestinalis, C. pylori, and "C. upsaliensis". AB - The isoprenoid quinone contents of Campylobacter cryaerophila, C. cinaedi, C. fennelliae, C. hyointestinalis, C. pylori, and "C. upsaliensis" were determined by reverse-phase thin-layer and high-performance liquid chromatography. All six of these recently named Campylobacter species contained menaquinone-6 (MK-6), but only C. hyointestinalis and "C. upsaliensis" contained 2,[5 or 8]-dimethyl-3 farnesyl-farnesyl-1,4-naphthoquinone (*MK-6), a previously described novel menaquinone of the Campylobacter genus. C. cryaerophila, C. cinaedi, C. fennelliae, and C. pylori contained an unidentified quinone (Un-MK-6) with a molecular weight of 580 and a base peak ion of m/e = 225 by mass spectrometry but with chromatographic properties different from those of MK-6. *MK-6 and Un-MK-6 are important chemotaxonomic markers of Campylobacter and Campylobacter-like organisms. PMID- 2312690 TI - Ocular infection caused by Psychrobacter immobilis acquired in the hospital. AB - The name Psychrobacter immobilis recently has been proposed for a group of chiefly psychrotrophic, aerobic, gram-negative, nonmotile, oxidase-positive coccobacilli commonly found associated with fish, processed meat, and poultry products. This article reports an ocular infection in a 12-day-old newborn who acquired the infection in the hospital, probably because of frequent manipulations in a closed aerated incubator. Also, this report intends to alert microbiologists to opportunistic infections that might be confused with infections caused by unusual oxidase-positive, gram-negative diplococci and to the isolation of P. immobilis from a human infection. PMID- 2312691 TI - Evaluation of the prognostic indices in Legg-Calve-Perthes disease: statistical analysis of 116 hips. AB - The records of 100 patients (116 hips) with Legg-Calve-Perthes' (LCP) disease, with a minimum follow-up of 4 years and treated at the University Hospital, Pellenberg, were reviewed. Sex, Salter's, and Catterall's classifications and lateral subluxation were found to be important prognostic indices. Older children tended to do worse than younger children, but statistical significance could not be established. "Head at risk" factors other than lateral subluxation were found to be unimportant as prognostic indices. Salter's classification was found to be simple, accurate, and significant, and could be made quite early. In the future, this should be an important consideration when making decisions on the management of LCP. PMID- 2312692 TI - The Swedish experience with Salter's innominate osteotomy in the treatment of congenital subluxation and dislocation of the hip. AB - The results of 83 Salter's innominate osteotomies (i.o.) performed to correct congenital subluxation and dislocation of the hip joint in 76 patients were reviewed. The overall radiographic results were classified as excellent or good in 34 hips (41%) and as fair or failure in 49 hips (59%). The best results were obtained in subluxated hips, previously not treated or treated only with closed reduction, prior to i.o. in patients operated on before the age of 5 years. In that group of hips, excellent or good results were obtained in 18 of 20 hips (90%). The poorest results were obtained in hips with residual subluxation or dislocation after previous operation with a result of fair or failure obtained in 26 of 28 hips (93%). PMID- 2312693 TI - Chiari pelvic osteotomy in Perthes disease. AB - A retrospective study of 17 Chiari osteotomies performed on patients with Perthes disease who were followed until the end of growth is presented. The average age at operation was 8 years 9 months. Catterall grading was mainly group IV. Chiari osteotomy provided satisfactory femoral head coverage with a decreased acetabular index and a 19.6 degrees improvement of the Wiberg angle. Good femoral coverage was related to age at operation and the site of the osteotomy on the upper rim of the acetabulum. The postoperative result was less successful on younger patients or when the osteotomy was performed higher. At follow-up, the results of femoral head sphericity studied by Mose measurements were favorable under Catterall grading. PMID- 2312694 TI - Elastic stable intramedullary nailing in forearm shaft fractures in children: 85 cases. AB - The results of elastic stable intramedullary nailing (ESIN) of 85 forearm fractures in children are reported. A single curved nail was inserted into each forearm bone with closed reduction. Immediate mobilization was allowed postoperatively. In a 3 year 6 month follow-up of 76 patients, 92% had excellent results with a full range of movement. There were neither nonunions nor infections. ESIN is recommended in the treatment of displaced forearm fractures in children older than 10 years of age, and in younger children when conservative treatment fails. PMID- 2312695 TI - Congenital diastasis of the inferior tibiofibular joint. PMID- 2312696 TI - The knee in arthrogryposis multiplex congenita. AB - The functional, radiological, and ambulatory status of 30 patients (58 knees) with arthrogryposis multiplex congenita (AMC) were analyzed after a follow-up of 1-36 years. The muscular imbalance presented in many of these patients corresponded well to the type of deformity. The primary treatment was nonoperative in most cases. In spite of the initial promising results, a significant number of patients underwent operation for residual symptoms. Treatment of flexion contractures seems to be more discouraging than the treatment of extension contractures. On the other hand, the risk for degenerative arthritis seemed to be elevated, especially in the extension-contracture group. PMID- 2312697 TI - Treatment of leg length discrepancy by subtrochanteric shortening of the femur. PMID- 2312698 TI - Results of physical therapy for idiopathic clubfoot: a long-term follow-up study. AB - Physical therapy without anesthesia or plaster casts was used to treat 338 cases of clubfoot (CF). Our technique is based on progressive sequential manipulations at birth. We first reduce the varus and later the equinus component of the CF. The gentle stretches used in this technique are complemented by active physiotherapy stimulating the muscles, and then a simple splint is suited to the foot to fix its degree of realignment. When used alone, this technique achieves 77% good and fair results. In resistant cases, complementary surgery was used. We obtained 96% good and fair results. PMID- 2312700 TI - Tibial agenesis: a new rationale in management of type II--report of three cases with long-term follow-up. PMID- 2312699 TI - Role of talocalcaneal osteotomy in clubfoot surgery: results in 31 surgically treated feet. AB - The most important deformities in clubfeet can be demonstrated by simultaneous arthrography of the talonavicular and talocrural joints. In patients with a severe talar deformity, wedge osteotomy through the talar neck and calcaneus has been performed as a prerequisite for correction. Our series consisted of 20 patients with 31 idiopathic clubfeet with pronounced talar deformity. The mean observation time after osteotomy was 11 years 3 months. The principles and aims are described, as are the indications for talocalcaneal osteotomy. Results were good in 19 feet (60%), fair in six (20%), and poor in six (20%). PMID- 2312701 TI - Metaphyseal distraction for lower limb lengthening and correction of axial deformities. AB - Metaphyseal distraction with the Orthofix apparatus was performed on 10 patients (five femora and five tibiae). A retrospective review is presented. The follow-up time was 10-38 months. A satisfactory correction of leg length and axial deformity was achieved in all cases. There was no need for plating or bone grafting. All patients showed solid bony fusion at follow-up. Pin tract infections in seven patients resolved under antibiotic treatment. Problems of pin loosening and mechanical weakness of the distraction device are discussed. PMID- 2312702 TI - The epidemiology of "schooliosis". AB - Questionnaires submitted to children subsequent to school screening for scoliosis reveal that 13% of respondents recall being referred to a physician. This rate is considerably higher than the 3% referral rate reported by school health officials. The discrepancy points to misperceptions by students and their parents as a likely cause of "schooliosis, " a condition which brings a flood of normal children into the offices of orthopaedists and pediatricians. Correcting possible communications problems, rather than blaming the screening program, should ease the over-referral phenomenon and allow screening to continue at its present efficient levels. PMID- 2312703 TI - Brainstem evoked potentials for scoliosis surgery: a reliable method allowing use of halogenated anesthetic agents. AB - A predictable and accurate method of monitoring cord function during scoliosis surgery using somatosensory brainstem evoked potentials (SBEP) is described. This method allows the use of halogenated anesthetic agents, which are ideal for neuromuscular patients, but easily disrupt traditional cortical monitoring. Fifty eight children with idiopathic, neuromuscular, and syndrome related scoliosis were monitored with 51 true negative, one false negative, four true positive and two false positive results. The SBEP method is sensitive and effective for all types of scoliosis surgery, especially neuromuscular scoliosis. PMID- 2312704 TI - Scoliosis in pediatric spinal cord-injured patients. AB - One hundred thirty children who sustained spinal cord injuries between birth and age 21 years were reviewed to determine the progression rate of paralytic scoliosis and the effects of bracing and surgery. Patients were divided into two groups: those injured before and those injured after the adolescent growth spurt. Scoliosis developed in 97 and 52%, respectively. Bracing was effective in delaying progression in the preadolescent group. The progressive paralytic spinal deformity did not appear to be related to the level of injury. The older patient is at much less risk for paralytic scoliosis, but still requires routine examination. PMID- 2312705 TI - Telescoping intramedullary stabilization of the lower extremities for severe osteogenesis imperfecta. AB - Intramedullary extendable Bailey-Dubow nails were used for treatment of lower extremity deformities resulting from osteogenesis imperfecta. Sixteen patients had 56 nails placed in 48 long bones, including 18 revisions. All patients were braced postoperatively. The average duration of follow-up was 4.8 years. Nine patients who were nonambulatory preoperatively walked in braces postoperatively. Despite a high rate of complication, extendable nails provide correction of the angular deformities of osteogenesis imperfecta, decrease fracturing, and allow most previously nonambulatory children to walk. PMID- 2312706 TI - Results of slipped capital femoral epiphysis in the black population. AB - This retrospective study, based on a chart and radiographic review of blacks treated for slipped capital femoral epiphysis (SCFE), showed a 93.2% incidence of excellent or good results, and an incidence of only 2.3% of major complications with poor results. Blacks can generally be expected to have a good result after treatment of SCFE in both males and females with a low incidence of avascular necrosis (AVN) or acute cartilage necrosis (ACN). PMID- 2312707 TI - Supracondylar osteotomy of the humerus for correction of cubitus varus. AB - Reports of corrective procedures for cubitus varus (gunstock deformity) have emphasized the frequency of loss of position and significant complication. Modifications that have been made to the standard supracondylar osteotomy protocol include correction of the angular deformity only, without correction of rotation; an incomplete wedge osteotomy leaving the medial cortex intact by hinging the osteotomy shut on the intact cortex; and immobilization of the elbow in full extension with the forearm supinated. In a review of 16 patients following this protocol, 11 patients had excellent results, three had good results, and two had unsatisfactory results. PMID- 2312708 TI - Development of the foot in prenatal life in relation to idiopathic club foot. AB - The development of the human foot from the eighth to the twenty-first intrauterine week was studied in 147 specimens. The results documented a stage of "physiologic club foot" characterized by a medial deviation and plantigrade orientation of talar neck and head during the ninth week. At the same time, the calcaneus assumes a position of varus with the forefoot in adduction. By the eleventh week, the foot assumes a normal position. All findings during the stage of physiologic club foot closely resemble those of the intrinsic type of club foot. PMID- 2312709 TI - Prenatal development around the sustentaculum tali and its relation to talocalcaneal coalitions. AB - Twenty cartilaginous talocalcaneal bridges were found in 16 cases among 142 feet from 119 embryos and fetuses ranging from 7 to 20 weeks. The cartilaginous bridges were mainly located extraarticularly between the posteromedial portion of the sustentaculum tali and the corresponding part of the talus. The incidence of talocalcaneal bridges was high in the prenatal period, especially during the ninth and tenth week; it was much less common in older specimens. This condition is attributed to either failure of or delay in differentiation of mesenchymal tissue into more specialized tissue between the posterior portion of sustentaculum tali and the corresponding part of the talus during the 7 1/2-8 1/2 postovulatory weeks. PMID- 2312710 TI - Extraarticular subtalar arthrodesis: the dowel method. AB - The technique and results of extraarticular subtalar arthrodesis using the dowel method during the 10-year period between 1976 and 1986 were reviewed retrospectively. Fifty feet in 30 children underwent extraarticular subtalar arthrodesis for valgus deformity for diagnoses including meningomyelocele, idiopathic flatfoot, and cerebral palsy. The aims of the procedure were to correct the deformity, obtain a solid arthrodesis, and improve ambulation by reducing bracing requirements and eliminating pain. Results were excellent in 28 cases (56%), satisfactory in 15 (30%), and unsatisfactory in seven (14%). Intraoperative positioning error and simultaneous perineal tendon lengthening in children with cerebral palsy were the major sources of unsatisfactory results. PMID- 2312711 TI - V-Y plasty for correction of varus fifth toe. AB - V-Y plasty has been used for greater than 35 years for correction of the varus fifth toe. During this time, there has been no study of the results of this operation on children with long-term follow-up. We report the results of 20 operations in 16 children. The short-term results were good in 70%. However, postoperative review at a mean time of 2 years 1 month showed marked deterioration, with only 30% good results. V-Y plasty is not recommended for correction of the varus fifth toe. PMID- 2312712 TI - Diaphyseal primary subacute osteomyelitis in children. AB - Six patients with subacute diaphyseal osteomyelitis of 200 with acute osteomyelitis who were seen and treated at the Red Cross Children's Hospital in a 3-year period (1985-1987) are reported. All six patients had a history of a minimum of 2 weeks' duration and the radiographic picture of a linear periosteal reaction, which was either single or laminated. This radiographic picture was indistinguishable from round cell tumors of bone. The final diagnosis was established by a histology consistent with a subacute osteomyelitis. In two patients, a positive culture of Staphylococcus aureus was obtained. All of the patients healed after treatment with cloxacillin. Radiographic resolution was noted in all patients within 6 months of treatment. PMID- 2312713 TI - Surgical management of congenital and habitual dislocation of the patella. AB - Twelve patients with congenital dislocation of the patella (CDP) and 23 patients with habitual dislocation of the patella (HDP) were followed for 2-15 years after surgical stabilization of the patella. The underlying pathology in both conditions was contracture of the quadriceps mechanism, which was more severe in CDP. Surgical stabilization in most cases included an extensive lateral release, medial plication, and transfer of the lateral half of the patella tendon. Lengthening of the rectus femoris tendon was required in many cases. With appropriate operative procedures, satisfactory results were achieved in 36 of the 41 knees (87.8%). PMID- 2312714 TI - Intraarticular loose bodies in the adolescent hip: results of treatment of those recognized late. AB - Seven cases of intraarticular loose bodies, previously unrecognized, were treated with surgical removal of the fragment. The presence of an intraarticular loose body was suspected because of persistent pain, restriction of hip joint motion, and asymmetric widening of the medial clear space on an anteroposterior (AP) pelvic roentgenogram. The diagnosis was established by computed tomography (CT) scan. Surgical removal should yield a good to excellent result, even when performed late, as long as osteonecrosis is not present at the time of operation. PMID- 2312715 TI - Obturator dislocation as a complication of closed reduction of the congenitally dislocated hip: a report of two cases. AB - Two cases of inferior obturator dislocation complicating treatment of congenital hip dislocation with closed reduction are described. Abduction and hyperflexion appear to be predisposing factors in development of this complication. Application of skin traction before any attempt is made at reduction will lengthen contracted soft tissues and may convert the inferior dislocation to a more manageable position. Open reduction was necessary in both patients, and the results were considered good. PMID- 2312716 TI - Larsen syndrome: clinical features and treatment--a report of two cases. AB - The literature on reported clinical and radiographic findings of Larsen syndrome is reviewed in detail. Two patients with Larsen syndrome who exhibited previously unreported skeletal deformities and such characteristic features as flattened facies, palate defects, and multiple joint dislocations are reported. Persistent difficulties in wound healing are discussed. PMID- 2312717 TI - Normal immunoglobulin G (IgG) for therapeutic use (intravenous Ig) contain antiidiotypic specificities against an immunodominant, disease-associated, cross reactive idiotype of human anti-thyroglobulin autoantibodies. AB - Pooled normal polyspecific IgG for therapeutic use (IVIg) contain anti-idiotypes against idiotypic determinants expressed by autoantibodies from patients with a variety of autoimmune diseases. In the present study, antiidiotypes in IVIg are shown to recognize a cross-reactive idiotype on human anti-thyroglobulin (TG) autoantibodies, that was defined by heterologous antiidiotypic antibodies, termed anti-T44 antibodies. The T44 idiotype is located outside the antibody-combining site of anti-TG autoantibodies. F(ab')2 fragments from anti-T44 antibodies inhibited the binding of IVIg to affinity-purified F(ab')2 anti-TG autoantibodies. Anti-T44 antibodies bound to F(ab')2 fragments of patients' antibodies, which were retained on an affinity column of Sepharose-bound F(ab')2 fragments from IVIg, but not to F(ab')2 fragments from the effluent of the column. The T44 idiotype was expressed on antibodies that bound to IVIg from eight of nine patients with autoimmune thyroiditis, but not on IVIg-binding Igs from healthy individuals. A small amount of the T44 idiotype was also expressed on the fraction of IVIg that bound to itself upon affinity chromatography. The T44 idiotype was cross-reactive between antibodies from patients with autoimmune thyroiditis. Thus, IVIg contain antiidiotypic antibodies directed against an immunodominant disease-associated cross-reactive alpha-idiotype of human anti-TG autoantibodies. These results support the concept that IVIg may be beneficial in selected autoimmune diseases by modulating the function of the idiotypic network. PMID- 2312718 TI - Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. AB - The mechanisms by which bone resorbing osteoclasts form and are activated by hormones are poorly understood. We show here that the generation of oxygen derived free radicals in cultured bone is associated with the formation of new osteoclasts and enhanced bone resorption, identical to the effects seen when bones are treated with hormones such as parathyroid hormone (PTH) and interleukin 1 (IL-1). When free oxygen radicals were generated adjacent to bone surfaces in vivo, osteoclasts were also formed. PTH and IL-1-stimulated bone resorption was inhibited by both natural and recombinant superoxide dismutase, an enzyme that depletes tissues of superoxide anions. We used the marker nitroblue tetrazolium (NBT) to identify the cells that were responsible for free radical production in resorbing bones. NBT staining was detected only in osteoclasts in cultures of resorbing bones. NBT staining in osteoclasts was decreased in bones coincubated with calcitonin, an inhibitor of bone resorption. We also found that isolated avian osteoclasts stained positively for NBT. NBT staining in isolated osteoclasts was increased when the cells were incubated with bone particles, to which they attach. We confirmed the formation of superoxide anion in isolated avian osteoclasts using ferricytochrome c reduction as a method of detection. The reduction of ferricytochrome c in isolated osteoclasts was inhibited by superoxide dismutase. Our results suggest that oxygen-derived free radicals, and particularly the superoxide anion, are intermediaries in the formation and activation of osteoclasts. PMID- 2312719 TI - Effects of a cholecystokinin receptor antagonist on intestinal phase of pancreatic and biliary responses in man. AB - The present study was designed (a) to characterize the activity of loxiglumide as a peripheral cholecystokinin (CCK) antagonist in healthy human subjects, and (b) to determine whether CCK is a physiologic regulator of the intestinal phase of meal-stimulated exocrine pancreatic and biliary secretions in man. Intravenous loxiglumide (22 mumol/kg per h) was highly potent in antagonizing CCK8-induced pancreatic enzyme and bile acid secretion as well as pancreatic polypeptide release. The potency and selectivity of loxiglumide as an antagonist of CCK provides the tool for evaluating the role of CCK as a physiological mediator of meal-induced pancreatic and biliary responses in humans. Infusion of a liquid test meal into the duodenum evoked an immediate response of pancreatic enzyme and bilirubin outputs, respectively. Intravenous loxiglumide significantly inhibited the meal-induced pancreatic amylase output by 63% (P less than 0.05), lipase output by 43% (P less than 0.05), and bilirubin output by 59% (P less than 0.05). These data suggest that CCK is a physiological mediator of the intestinal phase of meal-stimulated pancreatic and biliary responses. PMID- 2312720 TI - Accumulation of hyaluronan (hyaluronic acid) in myocardial interstitial tissue parallels development of transplantation edema in heart allografts in rats. AB - By using biotin-labeled proteoglycan core protein, hyaluronan (hyaluronic acid; HA) was visualized in rat heart grafts at different times (2, 4, and 6 d) after transplantation. In normal, nontransplanted hearts HA was present in the adventitia of arteries and veins and in the myocardial interstitial tissue. An increased accumulation of HA was evident in the edematous interstitial tissue, infiltrated with lymphocytes, on day 4 after allogeneic transplantation, and was even more pronounced by day 6. No apparent increase in HA was seen in syngeneic grafts. Biochemical assay of HA in heart tissue demonstrated that the myocardial content of HA had increased 60% by day 2 after transplantation in allogeneic as well as syngeneic grafts, indicating that surgical trauma may induce some HA accumulation in heart grafts. The extractable amount of HA declined during the following days in the syngeneic grafts, but increased progressively during the development of rejection in the allogeneic grafts, and increased on average three times by day 6. The relative water content also increased progressively during rejection of allogeneic grafts and correlated with the HA accumulation. The interstitial accumulation of HA, a glycosaminoglycan with unique water-binding qualities, is presumably implicated in the development of interstitial edema during rejection of heart grafts. PMID- 2312722 TI - Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo. AB - The mechanisms responsible for changes in myocardial contractility during regional ischemia are unknown. Since changes in high-energy phosphates during ischemia are sensitive to reductions in myocardial blood flow, it was hypothesized that myocardial function under steady-state conditions of graded regional ischemia is closely related to changes in myocardial high-energy phosphates. Therefore, phosphorus-31 nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional subendocardial blood flow, high-energy phosphates, pH, and myocardial segment shortening were made during various degrees of regional ischemia in which subendocardial blood flow was reduced by 16-94%. During mild reductions in myocardial blood flow (subendocardial blood flow = 83% of nonischemic myocardium), only the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), Pi, and [H+] were significantly changed from control. PCr, ATP, and PCr/ATP were not significantly reduced from control with mild reductions in blood flow. Changes in myocardial segment shortening were most closely associated with changes in PCr/Pi (r = 0.94). Pi and [H+] were negatively correlated with segment shortening (r = -0.64 and -0.58, respectively) and increased over twofold when blood flow was reduced by 62%. Thus, these data demonstrate that PCr/Pi is sensitive to reductions in myocardial blood flow and closely correlates with changes in myocardial function. These data are also consistent with a role for Pi or H+ as inhibitors of myocardial contractility during ischemia. PMID- 2312721 TI - Experimental non-O group 1 Vibrio cholerae gastroenteritis in humans. AB - In this study, 27 volunteers received one of three non-O group 1 Vibrio cholerae strains in doses as high as 10(9) CFU. Only one strain (strain C) caused diarrhea: this strain was able to colonize the gastrointestinal tract, and produced a heat-stable enterotoxin (NAG-ST). Diarrhea was not seen with a strain (strain A) that colonized the intestine but did not produce NAG-ST, nor with a strain (strain B) that produced NAG-ST but did not colonize. Persons receiving strain C had diarrhea and abdominal cramps. Diarrheal stool volumes ranged from 154 to 5,397 ml; stool samples from the patient having 5,397 ml of diarrhea were tested and found to contain NAG-ST. The median incubation period for illness was 10 h. There was a suggestion that occurrence of diarrhea was dependent on inoculum size. Immune responses to homologous outer membrane proteins, lipopolysaccharide, and whole-cell lysates were demonstrable with all three strains. Our data demonstrate that V. cholerae of O groups other than 1 are able to cause severe diarrheal disease. However, not all strains are pathogenic for humans: virulence of strain C may be dependent on its ability both to colonize the intestine and to produce a toxin such as NAG-ST. PMID- 2312723 TI - Impaired response of fibroblasts from patients with hyperapobetalipoproteinemia to acylation-stimulating protein. AB - Acylation-stimulating protein (ASP) is a small, basic, human plasma protein that markedly stimulates triglyceride synthesis in human adipocytes and cultured human skin fibroblasts. The present studies examine the response to ASP of cultured skin fibroblasts from normal subjects patients with hyperapobetalipoproteinemia, patients with familial hypercholesterolemia, and patients with hypertriglyceridemia without hyperapobetalipoproteinemia. Triglyceride synthesis induced by ASP did not differ significantly among the normals, the patients with familial hypercholesterolemia, and the patients with hypertriglyceridemia with normal low density lipoprotein (LDL) apolipoprotein B levels; however, on average, it was markedly reduced in the patients with hyperapobetalipoproteinemia. In all groups studied, evidence of specific saturable binding of radioiodinated ASP was present. Binding, however, was significantly reduced in the groups with hyperapobetalipoproteinemia whereas the other three groups were indistinguishable. By contrast, LDL-specific binding was reduced only in the patients with familial hypercholesterolemia. There was a significant direct relation between the degree of ASP binding and the triglyceride synthesis inducible by ASP. In addition, with the exception of the patients with familial hypercholesterolemia, there was an inverse relation between both ASP-specific binding and ASP-induced triglyceride synthesis in fibroblasts to LDL levels in plasma whereas no relation was evident to plasma high density lipoprotein and very low density lipoprotein. PMID- 2312724 TI - Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. AB - The cells that make up blood vessel walls appear to participate actively in local immune and inflammatory responses, as well as in certain vascular diseases. We tested here whether smooth muscle cells (SMC) can produce the important inflammatory mediator IL6. Unstimulated SMC in vitro elaborated 5 X 10(3) pg recIL6/24h (i.e., biological activity equivalent to 5 X 10(3) pg recombinant IL6 (recIL6), as determined in B9-assay with a recIL6 standard). Several pathophysiologically relevant factors augmented IL6 release from SMC including 10 micrograms LPS/ml (10(4) pg recIL6), 10 ng tumor necrosis factor/ml (4 X 10(4) pg recIL6), and most notably 10 ng IL1/ml (greater than or equal to 3.2 X 10(5) pg recIL6). Production of IL6 activity corresponded to IL6 mRNA accumulation and de novo synthesis. SMC released newly synthesized IL6 rapidly, as little metabolically labeled material remained cell-associated. In supernatants of IL1 stimulated SMC, IL6 accounted for as much as 4% of the secreted proteins. In normal vessels SMC seldom divide, but SMC proliferation can occur in hypertension or during atherogenesis. We therefore tested the relationship between IL6 production and SMC proliferation in response to platelet-derived growth factor (PDGF) in vitro. Quiescent SMC released scant IL6 activity, whereas PDGF (1-100 ng/ml) produced concentration-dependent and coordinate enhancement of SMC proliferation and IL6 release (linear regression of growth vs. IL6 release yielded r greater than 0.9). IL6 itself neither stimulated nor inhibited SMC growth or IL6 production. Intact medial strips studied in short-term organoid culture produced large quantities of IL6, similar to the results obtained with cultured SMC. These findings illustrate a new function of vascular SMC by which these cells might participate in local immunoregulation and in the pathogenesis of various important vascular diseases as well as in inflammatory responses generally. PMID- 2312726 TI - Calcium oscillations index the extent of calcium loading and predict functional recovery during reperfusion in rat myocardium. AB - Delayed recovery of contractile function after myocardial ischemia may be due to prolonged recovery of high-energy phosphates, persistent acidosis, increased inorganic phosphate, and/or calcium loading. To examine these potential mechanisms, metabolic parameters measured by 31P nuclear magnetic resonance spectroscopy, and spontaneous diastolic myofilament motion caused by sarcoplasmic reticulum-myofilament calcium cycling indexed by the scattered light intensity fluctuations (SLIF) it produces in laser beam reflected from the heart, were studied in isolated atrioventricularly blocked rat hearts (n = 10) after 65 min of ischemia at 30 degrees C. All metabolic parameters recovered to their full extent 5 min after reperfusion. Developed pressure evidenced a small recovery but then fell abruptly. This was accompanied by an increase in end diastolic pressure to 37 +/- 5 mm Hg and a fourfold increase in SLIF, to 252 +/- 58% of baseline. In another series of hearts initial reperfusion with calcium of 0.08 mM prevented the SLIF rise and resulted in improved developed pressure (74 +/- 3% vs. 39 +/- 13% of control), and lower cell calcium (5.9 +/- 3 vs. 10.3 +/- 1.4 mumol/g dry wt). Thus, during reperfusion, delayed contractile recovery is not associated with delayed recovery of pH, inorganic phosphate, or high-energy phosphates and can be attributed, in part, to an adverse effect of calcium loading which can be indexed by increased SLIF occurring at that time. PMID- 2312725 TI - Amplification of T cell blastogenic responses in healthy individuals and patients with acquired immunodeficiency syndrome. AB - Human immunodeficiency virus (HIV) infection is associated with a profound impairment of T cell function. Hence, enhancement of T cell reactivity to viral and bacterial antigens is important in the treatment of patients with AIDS. To develop tools for amplifying T cell reactivity, we have immunized mice with human helper T cell clones and selected monoclonal antibodies (MAbs) that enhance in vitro blastogenic responses. MAb NDA5, which recognizes the leukocyte common antigen CD45, amplifies human T cell responses to mitogens and soluble antigens including HIV-1 glycoprotein (gp)-120 and peptides derived from the HIV-1 gp-120 sequence. In the presence of MAb NDA5, peripheral blood mononuclear cells (PBMC) from healthy, HIV-1-seronegative individual displayed augmented blastogenic responses to HIV-1 gp-120 and to HIV-1 gp-120 synthetic peptides. In vitro memory responses to various vaccines and to alloantigens were also enhanced in cultures with MAb. Similarly, the response of PBMC from AIDS patients to pokeweed mitogen, HIV-1 gp-120, and tetanus toxoid was enhanced with MAb NDA5. The finding that the in vitro immune response of patients with AIDS can be amplified with MAb NDA5, suggests that the in vivo immune response of immunodeficient individuals can also be enhanced. PMID- 2312727 TI - Ultrastructural localization of cytochrome b in the membranes of resting and phagocytosing human granulocytes. AB - Affinity-purified rabbit anti-neutrophil cytochrome b light or heavy chain antibodies were used to immunocytochemically and biochemically localize cytochrome b in neutrophils and eosinophils. The antibodies were monospecific, recognizing polypeptides of 91 and 22 kD, respectively, on Western blots of whole neutrophil extracts. The antibodies were used in Western blot analysis of subcellular fractions of purified neutrophils to confirm that the distribution of cytochrome b spectral absorbance matched that of the two subunits. Thin sections of cryofixed, molecular distillation-dried granulocytes were labeled with the anti-cytochrome b antibodies, followed by incubation with biotin-conjugated secondary antibody, and final labeling with streptavidin-conjugated colloidal gold. Electron microscopy revealed that the cytochrome b light and heavy chains were localized primarily (80%) to 0.1-0.2-micron round or elliptical granule-like structures in neutrophils and 0.4-0.5-micron granules in eosinophils. Approximately 20% of the cytochrome b was localized to the surface, confirming the subcellular fractionation studies. Double staining experiments on the neutrophils, using polyclonal rabbit anti-lactoferrin antibody, indicated that the cytochrome-bearing structures also contained lactoferrin and thus were specific granules. When the analysis was performed on neutrophils that had phagocytosed Staphylococcus aureus, cytochrome b was found in the phagosomal membrane adjoining the bacterial cell wall. PMID- 2312728 TI - Phosphorus-31 nuclear magnetic resonance analysis of transient changes of canine myocardial metabolism in vivo. AB - The time course of the relative myocardial phosphocreatine and adenosine triphosphate contents (PCr/ATP) during step changes in heart rate in vivo was studied in 14 dogs using 31P nuclear magnetic resonance (NMR) to determine if transient changes in the high energy phosphates occur with changes in cardiac work. Coronary sinus blood flow (CF), oxygen consumption (MVO2), and NMR data were simultaneously measured during brief (approximately 3 min), paced increases in heart rate in these open chest animals. 31P spectra were collected with a time resolution of 15-16 s (PCr signal to noise 22-41:1). Paced tachycardia associated with increased CF and MVO2 had no significant transient or sustained effect on PCr/ATP. Higher heart rates, associated with decreased CF and blood pressure, caused rapid decreases of PCr/ATP that were reversible upon return to control rates. These data indicate that there are no transient changes in 31P metabolites (on a 15-16-s time base) during step changes in cardiac work associated with increased CF. This lack of change demonstrates that ATP hydrolysis and production are closely matched and that the feedback mechanism linking these processes occurs rapidly with no detectable transient change in the phosphate metabolites. In contrast, when the CF response to tachycardia is insufficient PCr is quickly depleted. This latter result suggests that the PCr/ATP ratio may be a sensitive, rapidly responding indicator of coronary supply/demand mismatching in vivo. PMID- 2312729 TI - Plasma native and peptidase-derivable Met-enkephalin responses to restraint stress in rats. Adaptation to repeated restraint. AB - Met-enkephalin and related proenkephalin A-derived peptides circulate in plasma at picomolar concentration as free, native pentapeptide and at nanomolar concentration in cryptic forms. We have optimized conditions for measurement of immunoreactive Met-enkephalin in plasma and for generation by trypsin and carboxypeptidase B of much greater amounts of total peptidase-derivable Met enkephalin in plasma of rats, dogs, and humans. Free Met-enkephalin (11 pM) is constituted by native pentapeptide and its sulfoxide. Characterization of plasma total Met-enkephalin derived by peptidic hydrolysis revealed a small amount (38 pM) of Met-enkephalin associated with peptides of molecular mass less than 30,000 D, and probably derived from proenkephalin A, but much larger amounts of Met enkephalin associated with albumin (1.2 nM) and with a globulin-sized protein (2.8 nM). Thus, plasma protein precursors for peptidase-derivable Met-enkephalin differ structurally and chemically from proenkephalin A. Met-enkephalin generated from plasma by peptidic hydrolysis showed naloxone-reversible bioactivity comparable to synthetic Met-enkephalin. Prolonged exposure of adult, male rats to restraint stress produced biphasic plasma responses, with peaks occurring at 30 s and 30 min in both free native and total peptidase-derivable Met-enkephalin. Repeated daily exposure to this 30-min stress resulted in adaptive loss of responses of both forms to acute restraint. Initial plasma responses of Met enkephalin paralleled those of epinephrine and norepinephrine, but subsequently showed divergence of response. In conclusion, Met-enkephalin circulates in several forms, some of which may be derived from proteins other than proenkephalin A, and plasma levels of both free native, and peptidase-derivable Met-enkephalin are modulated physiologically. PMID- 2312730 TI - Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements. AB - Epidermal cholesterol biosynthesis is regulated by barrier function. We quantitated the amount and activation state (phosphorylation-dephosphorylation) of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, in epidermis before and after barrier disruption. In murine epidermis we found high enzyme activity (1.75 +/- 0.02 nmol/min per mg protein). After acute barrier disruption, enzyme activity began to increase after 1.5 h, reaching a maximum increase by 2.5 h, and returned to normal by 15 h. Chronic barrier disruption increased total enzyme activity by 83%. In normal epidermis, measurement of HMG CoA reductase activity in microsomes isolated in NaF- vs. NaCl containing buffers demonstrated that 46 +/- 2% of the enzyme was in the active form. After acute or chronic barrier disruption, a marked increase in the percentage of HMG CoA reductase in the active form was observed. Acute disruption increased enzyme activation state as early as 15 min, reaching a maximum after 2.5 h, with an increase still present at 15 h, indicating that changes in activation state had a close temporal relationship with barrier function. Increases in total HMG CoA reductase activity occurred only after profound barrier disruption, whereas changes in activation state occur with lesser degrees of barrier disruption. Artificial correction of barrier function prevented the increase in total HMG CoA reductase activity, and partially prevented the increase in enzyme activation. These results show that barrier requirements regulate epidermal cholesterol synthesis by modulating both the HMG CoA reductase amount and activation state. PMID- 2312731 TI - Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. Evidence for delayed plasma clearance of intestinal lipoproteins. AB - Postprandial vitamin A and intestinal lipoprotein metabolism was studied in 86 healthy men and women, aged 19-76 yr. Three independent experiments were carried out. In the first experiment, a supplement dose of vitamin A (3,000 retinol equivalents [RE]) was given without a meal to 59 subjects, aged 22-76 yr. In the second experiment, 20 RE/kg body wt was given with a fat-rich meal (1 g fat/kg body wt) to seven younger subjects (aged less than 50 yr) and seven older subjects (aged greater than or equal to 50 yr). In both experiments, postprandial plasma retinyl ester response increased significantly with advancing age (P less than 0.05). In the third experiment, retinyl ester-rich plasma was infused intravenously into nine young adult subjects (aged 18-30 yr) and nine elderly subjects (aged greater than or equal to 60 yr), and the rate of retinyl ester disappearance from plasma during the subsequent 3 h was determined. Mean (+/- SE) plasma retinyl ester residence time was 31 +/- 4 min in the young adult subjects vs. 57 +/- 8 min in the elderly subjects (P less than 0.05). These data are consistent with the concept that increased postprandial plasma retinyl ester concentrations in older subjects are due to delayed plasma clearance of retinyl esters in triglyceride-rich lipoproteins of intestinal origin. PMID- 2312732 TI - Adrenergic regulation of lipolysis in situ at rest and during exercise. AB - The adrenergic regulation of lipolysis was investigated in situ at rest and during standardized bicycle exercise in nonobese healthy subjects, using microdialysis of the extracellular space in subcutaneous adipose tissue. The glycerol concentration was about two times greater in adipose tissue than in venous blood. At rest, the glycerol concentration in adipose tissue was rapidly increased by 100% (P less than 0.01) after the addition of phentolamine to the ingoing perfusate, whereas addition of propranolol did not alter the adipose tissue glycerol level. Glycerol in adipose tissue and plasma increased during exercise and decreased in the postexercise period. Propranolol in the perfusate almost completely inhibited the increase in the tissue dialysate glycerol during the exercise-postexercise period. Phentolamine, however, was completely ineffective in this respect. During exercise, the lipolytic activity was significantly more marked in abdominal than in gluteal adipose tissue; this was much more apparent in women than in men. Thus, in vivo lipolysis in subcutaneous adipose tissue is regulated by different adrenergic mechanisms at rest and during exercise. Alpha-adrenergic inhibitory effects modulate lipolysis at rest, whereas beta-adrenergic stimulatory effects modulate lipolysis during exercise. In addition, regional differences in lipolysis are present in vivo during exercise, which seem governed by factors relating to sex. PMID- 2312734 TI - Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. AB - The effects of glucose on endothelium-dependent responses and vasoactive prostanoid production were determined by incubating isolated rabbit aortae in control (5.5 or 11 mM) or elevated (44 mM) glucose for 6 h to mimic euglycemic and hyperglycemic conditions. Rings of aortae incubated in elevated glucose, contracted submaximally by phenylephrine, showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with the aortae incubated in control glucose. Treatment with indomethacin, a cyclooxygenase inhibitor, or SQ29548, a prostaglandin H2/thromboxane A2 receptor antagonist, restored acetylcholine relaxations of rings in elevated glucose to normal, while these agents had no effect on the relaxation of rings incubated in control glucose. Aortae incubated with mannose (44 mM) as a hyperosmotic control relaxed to acetylcholine normally. The relaxations in response to A23187 and sodium nitroprusside were not different between rings exposed to control and elevated glucose. Radioimmunoassay measurements showed a significant increase in acetylcholine-stimulated release of thromboxane A2 and prostaglandin F2 alpha in aortae with, but not without endothelium incubated with elevated, but not with control glucose. Thus a possible mechanism for endothelium dysfunction in diabetes mellitus is the hyperglycemia-induced increased generation of endothelium-derived vasoconstrictor prostanoids. PMID- 2312733 TI - Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties. AB - Two 29-kD polypeptides, azurocidin and p29b, were purified to homogeneity from human neutrophils by acid extraction of azurophil granule membrane-associated material followed by gel filtration and reverse-phase chromatography. Azurocidin and p29b share NH2-terminal sequence homology with each other as well as with elastase, cathepsin G, and other serine proteases. p29b bound [3H]diisopropyl fluorophosphate and hydrolyzed elastin, casein, and hemoglobin. A peptide substrate for p29b could not be identified. Azurocidin neither bound [3H]diisopropyl fluorophosphate nor hydrolyzed any of the proteins, peptides, or esters tested. In microbicidal assays, purified azurocidin was comparable to p29b in activity against Escherichia coli, Streptococcus faecalis, and Candida albicans. The antimicrobial activity of azurocidin was enhanced under mildly acidic conditions, but was inhibited in a dose-dependent manner by NaCl, CaCl2, or serum. Immunoblot analysis with monospecific antibodies localized greater than 90% of the azurocidin and greater than 75% of the p29b to azurophil granule-rich fractions of PMN lysates. Immunoelectron microscopy confirmed the localization of azurocidin to the azurophil granules. Azurocidin associated with the azurophil granule membrane, but did not appear to be an integral membrane protein. Thus, azurocidin and p29b are members of a family of serine protease homologs stored in azurophil granules and may play a role in inflammatory and antimicrobial processes involving PMN. PMID- 2312735 TI - Familial hypobetalipoproteinemia caused by a mutation in the apolipoprotein B gene that results in a truncated species of apolipoprotein B (B-31). A unique mutation that helps to define the portion of the apolipoprotein B molecule required for the formation of buoyant, triglyceride-rich lipoproteins. AB - Apolipoprotein B-100 has a crucial structural role in the formation of VLDL and LDL. Familial hypobetalipoproteinemia, a syndrome in which the concentration of LDL cholesterol in plasma is abnormally low, can be caused by mutations in the apo B gene that prevent the translation of a full-length apo B-100 molecule. Prior studies have revealed that truncated species of apo B [e.g., apo B-37 (1728 amino acids), apo B-46 (2057 amino acids)] can occasionally be identified in the plasma of subjects with familial hypobetalipoproteinemia; in each of these cases, the truncated apo B species has been a prominent protein component of VLDL. In this report, we describe a kindred with hypobetalipoproteinemia in which the plasma of four affected heterozygotes contained a unique truncated apo B species, apo B-31. Apolipoprotein B-31 is caused by the deletion of a single nucleotide in the apo B gene, and it is predicted to contain 1425 amino acids. Apolipoprotein B 31 is the shortest of the mutant apo B species to be identified in the plasma of a subject with hypobetalipoproteinemia. In contrast to longer truncated apo B species, apo B-31 was undetectable in the VLDL and the LDL; however, it was present in the HDL fraction and the lipoprotein-deficient fraction of plasma. The density distribution of apo B-31 in the plasma suggests the possibility that the amino-terminal 1425 amino acids of apo B-100 are sufficient to permit the formation and secretion of small, dense lipoproteins but are inadequate to support the formation of the more lipid-rich VLDL and LDL particles. PMID- 2312736 TI - Glucose transporter levels in spontaneously obese (db/db) insulin-resistant mice. AB - In the present study we examined mRNA and protein levels for the muscle/adipose tissue glucose transporter (GLUT-4) in various tissues of spontaneously obese mice (C57BL/KsJ, db/db) and their lean littermates (db/+). Obese (db/db) mice were studied at 5 wk of age, when they were rapidly gaining weight and were severely insulin resistant, evidenced by hyperglycemia (plasma glucose 683 +/- 60 vs. 169 +/- 4 mg/dl in db/+, P less than 0.05) and hyperinsulinemia (plasma insulin 14.9 +/- 0.53 vs. 1.52 +/- 0.08 ng/ml in db/+, P less than 0.05). The GLUT-4 mRNA was reduced in quadriceps muscle (67.5 +/- 8.5%, P = 0.02), but unaltered in adipose tissue (120 +/- 19%, NS), heart (95.7 +/- 6.1%, NS), or diaphragm (75.2 +/- 12.1%, NS) in obese (db/db) mice relative to levels in lean littermates. The GLUT-4 protein, measured by quantitative immunoblot analysis using two different GLUT-4 specific antibodies, was not different in five insulin sensitive tissues including diaphragm, heart, red and white quadriceps muscle, and adipose tissue of obese (db/db) mice compared with tissue levels in lean littermates; these findings were consistent when measured relative to tissue DNA levels as an index of cell number. These data suggest that the marked defect in glucose utilization previously described in skeletal muscle of these young obese mice is not due to a decrease in the level of the major muscle glucose transporter. An alternate step in insulin-dependent activation of the glucose transport process is probably involved. PMID- 2312737 TI - Acetylation pharmacogenetics. The slow acetylator phenotype is caused by decreased or absent arylamine N-acetyltransferase in human liver. AB - The biochemical basis underlying the genetic polymorphism of drug N-acetylation was investigated using a combination of in vivo and in vitro assays for arylamine N-acetyltransferase (NAT) activity and content in human liver. The acetylator phenotype of 26 surgical patients was determined using caffeine as an innocuous probe drug by measurement of the 5-acetyl-amino-6-formylamino-3-methyluracil to 1 methylxanthine molar ratio in urine. Liver wedge biopsies from these patients and livers from 24 organ donors were then used for measurement of N-acetyltransferase activity with the substrate sulfamethazine and for quantitation of immunoreactive N-acetyl-transferase protein. In vivo (caffeine metabolites in urine) and in vitro (sulfamethazine acetylation) measures of N-acetyl-transferase activity correlated very highly (r = 0.98). Moreover, in all subjects tested, slow acetylation both in vivo and in vitro was associated with a decrease in the quantity of immunodetectable N-acetyltransferase protein in liver cytosol relative to that seen in cytosols from rapid acetylator livers. Two kinetically distinct enzyme activities, designated NAT-1 and NAT-2, were partially purified from low- and high-activity livers and their relationship to acetylator status was determined. Low acetylation capacity was related to decreases in the liver content of both of these immunologically related proteins. The results demonstrate that genetically defective arylamine N-acetylation is due to a parallel decrease in the quantity of two structurally and functionally similar acetylating enzymes. PMID- 2312738 TI - Frontal cephalometric study of dentofacial morphology in children with bilateral clefts of lip, alveolus and palate. AB - The transverse dentofacial morphology of 36 children with bilateral cleft lip, alveolus and palate was studied by means of a frontal proportional cephalometric analysis at the ages of three, eight and twelve years. Comparison of the variables of the cleft group was made with the normal dimensions as obtained from the Bolton cephalometric templates. The results indicated that the BCLP group presented characteristics and significant differences from the normal in the dimensions of the nasal septum width and the mandibular intergonial width as they are both related to the interorbital width, the maxillary intermolar width as it is related to the mandibular intermolar width and the maxillary width as it is related to the mandibular intergonial width at all three ages. The maxillary base and intermolar widths, although significantly different at the ages of three and eight years, showed no significant deviation from normality at the age of twelve years. Following orthodontic treatment between the ages of seven to twelve years, the maxillary intermolar width of the treated subgroup was significantly larger than in the untreated subjects. PMID- 2312739 TI - Autogenous rib graft for reconstruction of alveolar bone defects in cleft patients. Long-term follow-up results. AB - In a retrospective study (mean follow-up 76 months), the use of a free autogenous rib graft for reconstruction of anterior residual bone defects in seventeen cleft patients is evaluated on a long term basis. The results show recurrence of a palatal oronasal fistula in 2 out of 17 patients. 6 patients had acceptable results, while 9 had good to excellent scores at all sites. The costal graft material does not prevent permanent upper cuspids from erupting into this bone, after its incorporation. It is concluded that autogenous rib bone is a good material for secondary bone grafting of the residual alveolar and palatal defect in cleft patients. PMID- 2312740 TI - Secondary correction of bilateral cleft lip nose deformity. AB - For correction of the bilateral cleft lip nasal deformity, a modified bilateral reverse U incision is used in combination with a short, forked flap; by using this combination, satisfactory lengthening of the columella, preserving the natural pout of the lip, can be obtained. We have applied this method to 12 cases undergoing secondary repair of bilateral cleft lip in the past 3 years, and the results of this treatment, along with representative photographs of some of our patients, are presented herein. PMID- 2312743 TI - Mandibular invasion by oral squamous cell carcinoma. Clinical aspects. AB - In this paper we have tried to correlate the clinical and radiological aspects to the histological findings in squamous cell carcinomas of the oral cavity, in relation to bone involvement in the mandible. 52 patients were analyzed and we conclude that there is a positive indication for mandible sparing surgery, even if there is fixation to the jaw or radiologically visible bone involvement. PMID- 2312742 TI - Numerical analysis of the human nostril by the Fourier series. AB - Fourier series has been applied in a numerical analysis of the human nostril morphology. The relationship between the nostril form and the Fourier coefficients was examined: the constant affected the size, the first term determined the roundness, and the second term determined the flatness of the morphology. The inclination of the apse line was calculated from the phase of the second term. Ninety-five standardized nostril photographs were analyzed by Fourier series: 48 of adult Japanese females and 47 of German females. The German nostril was larger in size, flatter in shape, and the apse line closer to the sagittal plane than the Japanese counterpart. As a clinical application of nostril digitization, pre- and post-operative cleft lip noses were analyzed. Fourier analysis has proved to be useful in a numerical evaluation of morphological differences of, and post-operative changes made to, the nostril. PMID- 2312741 TI - Three-dimensional analysis of facial morphology before and after orthognathic surgery. AB - A method for three-dimensional analysis of the facial hard- and soft-tissue morphologies is described. The soft-tissue analysis consisted of calculating three-dimensional values of reference points on the face by perspective transformation of their values in two pairs of photographs, taken simultaneously, from the right and left sides of the face. The shape of the mandible was analyzed three-dimensionally by the simultaneously taken frontal and lateral cephalograms. The hard- and soft-tissue changes were analyzed with the method in 28 patients in whom mandibular prognathism had been corrected by orthognathic surgery. The magnitude of the surgically-produced soft tissue volumetric changes in the anterior mandibular region was proportional to the posterior movement of the mandible. Asymmetry of the face also improved in response to correction of lateral deviation of the mandible and a close correlation between the directional indices of asymmetry of the hard and soft tissues was observed. Thus, the method was found to be quite useful for the analysis of facial morphology in jaw deformity. PMID- 2312744 TI - The "double faced" pectoralis major island flap. A valuable alternative in full thickness cheek reconstruction. AB - Experience with cheek reconstruction after resection, using a single pectoralis major island flap with its inner surface previously split-skin grafted, is presented. No complications were observed in the initial series of 4 cases. The method appears to be a valuable alternative in selected cases, whenever local tissues cannot be used for reconstruction. PMID- 2312745 TI - Observer variability in histopathological reporting of transitional cell carcinoma and epithelial dysplasia in bladders. AB - Sections from 90 urinary bladder biopsy specimens were examined by 11 consultant histopathologists with varying experience to determine the appropriateness of existing pathology terminology. Analysis with kappa statistics showed fair to good agreement in the grading and staging of transitional cell carcinoma. There was also reasonable agreement in the diagnosis of high grade dysplasia in random biopsy specimens from the urothelium adjacent to the neoplasm, but very poor agreement for lesser degrees of dysplasia. It is concluded that the present classification of bladder carcinomata is reliable and that pathologists can determine stage with a high degree of reproducibility and grade with a fair degree of reproducibility. PMID- 2312746 TI - Ultrastructural analysis of fine needle aspirates from benign breast lesions. AB - Thirty six fine needle aspirates from various types of benign breast lesions were examined by electron microscopy and correlated with their cytological appearances. In all cases the parenchyma consisted of clumps of cohesive cells with the ultrastructural features of epithelial cells. In many cases, particularly from fibroadenomas, the parenchyma consisted of single layers of polarised epithelial cells showing lumen formation. Similar arrays of apocrine epithelial cells were observed in 60% of fibrocystic lesions. The more solid clumps from hyperplastic lesions consisted of epithelial cells of variable shape and electron density with disorganised lumen formation. Irrespective of the type of lesion, the epithelial cells were not normally subtended by myoepithelial cells or basal lamina. The extraction process seems to result in a shearing between the epithelium and basal lamina with lysis of the myoepithelial cells. Most naked nuclei probably result from lysed myoepithelial cells. PMID- 2312747 TI - Lamina propria eosinophils and mast cells in ulcerative colitis: comparison between Asians and Caucasians. AB - To investigate the theory of hypersensitivity in the colonic mucosa of Asian patients with ulcerative colitis the rectal biopsy specimens of Asian and Caucasian patients presenting with colitis were selectively stained for both eosinophils and mast cells. Comparisons between ethnic groups were made as well as the correlation to the blood eosinophil count and two variables of active ulcerative colitis--the blood leucocyte count and serum orosomucoid concentration. No correlation was found in either group between circulating and tissue eosinophils and no ethnic difference was identified in the lamina propria differential cell densities. The leucocyte count and serum orosomucoid concentrations, however, were significantly higher in the Caucasians. In the Asian group a strong negative association was found between the lamina propria eosinophil density and serum orosomucoids; in the Caucasian group there was a positive association between all blood variables. It is concluded that different mechanisms occur in the two ethnic groups and in Asians these might not be reflected by the more orthodox indices of colonic inflammation. PMID- 2312748 TI - Thin basement membranes in minimally abnormal glomeruli. AB - The light microscopic, immunofluorescence, and electron microscopic appearances of renal biopsy specimens were reviewed and correlated with the clinical and laboratory findings in 61 patients in whom the findings were initially considered to be either normal or to show only minor non-specific abnormalities. In all cases this reassessment included quantitative measurement of glomerular basement membrane thickness by an orthogonal intercept technique. On the basis of the indication for biopsy, patients were classified into three groups: those with haematuria (group I, n = 41); those with a minor degree of proteinuria (group II, n = 16); and those without any urinary abnormality but in whom possible renal disease as a result of systemic disease was suspected (group III, n = 6). About half of the patients with haematuria had significantly thinner glomerular basement membranes than those in the other two groups, irrespective of the variable selected for assessment, and in three this was confirmed in follow up biopsy specimens. Follow up for up to eight years showed that in patients either with or without thin basement membranes haematuria commonly persisted, but the long term outlook in all three groups was otherwise good and no patient developed impaired renal function. PMID- 2312749 TI - Chronic carotid glomitis and the glomus pulmonale. AB - A histological study was made of the carotid bodies and glomus pulmonale in 50 consecutive subjects over the age of 50 years who came to necropsy to determine if chronic glomitis is confined to the carotid bodies or whether it also occurs in other glomera. Lymphoid aggregates and plasma cell activity were found in the glomus pulmonale just as they were in the carotid bodies. Chronic pulmonary glomitis sometimes occurred in association with chronic carotid glomitis and sometimes independently of this. The mean age of the affected subjects was 76 years in isolated pulmonary glomitis and 79 years in chronic carotid glomitis. Chronic carotid glomitis affected seven (14%) subjects and predominated in women (six to one). In the seven cases of isolated pulmonary glomitis women predominated five to two. Chronic glomitis seems to be a disease process which may affect at least two members of the non-chromaffin paraganglionic system, but it is not clear why focal chronic inflammation affects the glomus pulmonale of one person but not of another. PMID- 2312750 TI - Changes in alveolar macrophage, monocyte, and neutrophil cell profiles after smoke inhalation injury. AB - Thirty two fire victims with smoke inhalation, with or without burns, and 26 control subjects had bronchoalveolar lavage performed. Cell yields and differential cell counts were assessed. All patients and controls were cigarette smokers. Patients with smoke inhalation (SI) injury generally showed higher total bronchoalveolar lavage (BAL) cell yields, and this was significant on repeat lavage from 12 patients. The increase was almost entirely due to an increase in the proportion of neutrophils in patients with smoke inhalation alone (S) and those with cutaneous burns as well as smoke inhalation (S + B). On sequential lavage of 12 patients with smoke inhalation (SI) the proportion of neutrophils had increased; this was significantly higher than on initial lavage. Using various macrophage markers, the proportions of macrophage subgroups were determined. There was an increase in UCHM1 and RFD9 positive cells in each subgroup: the increase in UCHM1 positive cells was significant in patients with burns as well as smoke inhalation, and the increase in RFD9 positive cells was significant in patients with smoke inhalation alone. Assessment of the role of such cells in the development of acute lung injury (such as adult respiratory distress syndrome) may be important in our understanding of the mechanisms entailed. PMID- 2312751 TI - Assessment of oestrogen receptor content of breast carcinoma by immunohistochemical techniques on fixed and frozen tissue and by biochemical ligand binding assay. AB - The oestrogen receptor content of 61 breast carcinomas was assessed by biochemical ligand binding assay and three immunohistochemical techniques--a frozen section method (Abbott ER-ICA) and on paraffin wax sections after fixation by two methods. The two fixatives used were Carson's buffered formalin and methacarn, and a DNAse pretreatment of sections was used. Overall agreement for the immunohistochemical methods with the ligand binding technique were 95%, 85%, and 86% for the frozen, formalin, and methacarn methods, respectively. A semiquantitative staining score was performed and all three methods gave significant correlations of staining scores with biochemical ligand binding values. The frozen section method was best (r = 0.88) with the fixed tissue methods yielding poorer correlation coefficients. Several factors affected staining, including the nature of the fixative and variable activity of DNAse. It is concluded that immunohistochemical assessment of oestrogen receptor content on fixed tissue provides acceptable qualitative information but that standardisation of protocols for tissue processing will be necessary for optimal utility and especially for quantitative assessments. PMID- 2312752 TI - Small intestinal bacterial overgrowth in patients with chronic lymphocytic leukaemia. AB - As part of a study to assess the possible contribution of lymphoid infiltration of the gastrointestinal mucosa to occult blood loss or malabsorption 20 patients with chronic lymphocytic leukaemia (CLL) had a lactulose hydrogen breath test. In 10 cases (50%) a small intestinal peak was detected, suggesting small bowel bacterial overgrowth, and this was confirmed in seven patients by the positive culture of jejunal aspirate. Of the patients with a positive hydrogen breath test, radiological examination showed a duodenal diverticulum in two but no anatomical abnormalities in the other cases. There was no evidence of achlorhydria and transit times were normal. There was no difference in the incidence of hypogammaglobulinaemia among those patients with evidence of small intestinal bacterial overgrowth and those without. Seven patients with a positive hydrogen breath test, however, had undetectable secretory piece in their jejunal aspirates whereas this was present in all patients with a normal breath test who had local immunoglobulin concentrations measured (p less than 0.05), indicating that the small intestinal bacterial overgrowth may be due to impaired local immunity. PMID- 2312753 TI - Campylobacter pylori in the upper gastrointestinal tract of patients with HIV-1 infection. AB - Fifty one patients with human immuno-deficiency virus (HIV-1) infection who had been consecutively endoscoped for upper gastrointestinal symptoms were biopsied (stomach or duodenum, or both) and compared with 59 age and sex matched controls for the presence of Campylobacter pylori. In 28 (47%) of the control group but in only seven (14%) of the HIV seropositive patients were C pylori seen on histological examination (p less than 0.001, odds ratio 5.6, 95% confidence interval 2.2-14.5). Sixteen patients who were HIV antibody positive had other index diseases for the diagnosis of AIDS in the biopsy material and, when these were excluded, comparison with the control group still showed a significant difference; p less than 0.01, odds ratio 3.6, 95%, confidence interval 1.4-9.6. In this series, therefore, C pylori were far less common in HIV antibody positive patients than in controls. Among the HIV positive patients, a higher proportion of C pylori negative cases had AIDS but this trend was not significant. The findings of this study indicate that whatever abnormalities of cell mediated mucosal immunoregulation are caused by HIV infection, they do not seem to be important in the response to infection by C pylori. PMID- 2312755 TI - Distribution of Campylobacter pylori in the upper and lower gastrointestinal tract: a microbiological and histological study. PMID- 2312754 TI - Serological diagnosis of neurobrucellosis. AB - The presence of antibodies was determined in the serum and cerebrospinal fluid in six patients with neurobrucellosis using the Rose Bengal test, the microdilution agglutination test, and the Coombs' test. Four of the patients were followed up for more than three months. The Rose Bengal test and the microagglutination test were positive in cerebrospinal fluid in five of the six cases at some stage. The Coombs' test was positive in cerebrospinal fluid in every patient and in one was the only positive serological test. Cerebrospinal fluid positivity is not excluded by low titres or negative results of antibodies in the serum for any of the three methods. A Coombs' test or some equivalent must always be made on the cerebrospinal fluid to diagnose neurobrucellosis. PMID- 2312756 TI - Primary malignant melanoma of the oesophagus. PMID- 2312757 TI - Secondary tumour deposits in needle biopsy tracks: an underestimated risk? PMID- 2312758 TI - Statistics on microcomputers. PMID- 2312759 TI - Automated measurement of plasma viscosity using the Coulter Viscometer II. PMID- 2312760 TI - Dipstick urinalysis for bacteriuria. PMID- 2312761 TI - CLO in Meckel's diverticula. PMID- 2312762 TI - Drug delivery systems: 3B. Role of polymers in drug delivery. PMID- 2312763 TI - Altered hemodynamic response to isosorbide dinitrate in essential hypertension. AB - Relaxation produced by nitrates on venous, arteriolar, and large arterial vessels is well known but has never been studied in human hypertensive aortas studied in vivo. In this investigation, the effects of acute oral administration of 20 mg of isosorbide dinitrate were evaluated in 12 patients with sustained essential hypertension and nine normotensives of the same age. Noninvasive measurements of systolic, diastolic, and mean arterial pressure, carotid-femoral pulse wave velocity and aortic-arch diastolic diameter using suprasternal echocardiography were determined before and 3 hours after drug administration. In normal subjects, isosorbid dinitrate significantly decreased systolic blood pressure and pulse pressure but did not affect diastolic and mean arterial pressure. In contrast, in hypertensives, the same dosage of isosorbid dinitrate decreased together systolic, diastolic mean, and pulse pressure. In both populations, pulse wave velocity decreased significantly whereas aortic arch diastolic diameter increased markedly. The increase was observed mainly in normal subjects. The study provided evidence that (1) both in normal subjects and hypertensives, isosorbide dinitrate caused an increase in aortic diameter together with an increase in arterial distensibility; and (2) the changes in mean arterial pressure were significant only in hypertensives, indicating that the altered vasodilator response in essential hypertension is not endothelium-mediated. PMID- 2312764 TI - Pharmacodynamic dependent disposition of the angiotensin converting enzyme inhibitor, libenzapril. AB - Libenzapril, an angiotensin converting enzyme inhibitor, was administered to healthy male volunteers in a randomized, two-phase pharmacokinetic study. One phase compared the pharmacokinetics of a 4 mg intravenous infusion and 20 mg oral solution, and the other phase provided two additional intravenous infusions of 1.7 and 12 mg for comparison. The intravenous model-independent pharmacokinetic parameters MRTiv, Vss, CL, and CLr all exhibited dose dependence. The concentration dependent renal clearance was maximal at 83 mL/min and minimal at 32 mL/min following intravenous administration. The mechanism of libenzapril's self-inducible clearance appears to have a pharmacodynamic basis. The absolute bioavailability was estimated at less than 10% and the renal clearance following oral administration exhibited additional route dependency. PMID- 2312765 TI - Steady state pharmacokinetics of propranolol in Saudi Arabian patients and comparison with data for different populations. AB - The steady state pharmacokinetics of propranolol was examined in 48 Saudi Arabian patients chronically treated with oral doses [mean (SEM) = 85.8 (5) mg] of this drug. The mean (SEM) of the steady state concentration (Css) per mg/kg daily dose was 21.8 (3.1) ng.ml-1/mg.kg-1. A 6-fold variability in Css was observed between patients treated with 40 mg every 8 hours and 14-fold between patients treated with 40 mg twice daily. The frequency distribution of the apparent oral clearance (TCLor) of propranolol was bimodal with 88% of the patients showing TCLor of 18 to 372 l.hr-1 while the remainder had TCLor of 471 to 749 l.hr-1. The mean (SEM) of the TCLor per kg body weight for all 48 patients was 3.16 (0.38) l.hr-1.kg-1. Both Css and TCLor obtained for Saudi Arabian patients are not significantly different from those reported for subjects from Western populations. While Css increased proportionally (P less than .001) with dosing, a near-significant (P less than .06), inverse, linear relationship was found between age and TCLor. No significant effect of sex, body weight, or disease state (i.e., heart diseases, hypertension, depression, migraine) on Css or TCLor was detected. PMID- 2312766 TI - Experimental antiarteriosclerotic effects of calcium antagonists. PMID- 2312767 TI - The effects of enalapril on urinary protein excretion in patients with idiopathic membranous nephropathy. AB - High doses of the angiotensin converting enzyme inhibitor, captopril, is known to cause significant increases in urinary protein excretion in patients with idiopathic membranous nephropathy. To find whether other angiotensin converting enzyme inhibitors yield similar results, we prospectively examined the effect of enalapril in five consecutive patients with idiopathic membranous nephropathy, elevated arterial pressure, and proteinuria and compared them to age-matched controls receiving clonidine. Glomerular filtration rate, 24-hour urinary protein excretion, and arterial pressure were measured. All patients served as their own controls. Those who received enalapril demonstrated an initial increase in proteinuria (-0.3 +/- 0.7 delta gm/day, clonidine vs 3.9 +/- 0.9 delta gm/day, enalapril: P less than .05) despite similar decreases in arterial pressure (-18 +/- 6 delta mm Hg, clonidine vs -22 +/- 6 delta mm Hg, enalapril: NS) and glomerular filtration rate (-1.1 +/- 0.8 delta mL/min, clonidine vs -1.9 +/- 1.2 delta mL/min, enalapril: NS) when compared to the clonidine group. This increase in proteinuria, however, did not occur when these patients were rechallenged with enalapril. To our knowledge, this is the first report to document a significant increase in preexisting nephrotic range proteinuria following administration of nonsulfhydryl ACE inhibitor. This increase, however, appears to be unique to the initial treatment phase of the disease and does not affect long-term management. PMID- 2312768 TI - Hemofiltrability of H2-receptor antagonist, famotidine, in renal failure patients. AB - To determine if a new H2-receptor antagonist, famotidine, would be significantly removed by arteriovenous hemofiltration, we measured plasma concentrations and amounts of the drug recovered in ultrafiltrate during 18 sessions of an intermittent hemofiltration performed in five patients with renal failure receiving the repeated intravenous dosings of the drug (5-20 mg/day). Plasma and ultrafiltrate drug concentrations were determined by using a high performance liquid chromatography with fluorescent detection. The mean (+/- SD) amount of the drug removed by the procedure, which was performed at the mean ultrafiltration rate of 19.0 +/- 6.0 ml/min over the mean duration of 212 +/- 168 min, corresponded to 4.1 +/- 2.2% of the daily maintenance doses. There was a significant (r = 0.90, P less than .01) linear relationship between the hemofiltration clearance and the ultrafiltration rate, indicating that the sieving coefficient, an index filtration efficiency, for the drug was largely constant (i.e., 0.73 +/- 0.10) over the ranging filtration rates (i.e., 3.9-29.5 mL/min) employed in the present study. When the mean filtration efficiency of 0.73 obtained from the study is extrapolated into a 24-hour continuous arteriovenous hemofiltration performed at commonly used filtration rates (i.e., 6 12 ml/min), the 24-hour hemofiltration clearances are estimated to range from 4 to 9 ml/min. These clearance values are found to correspond to only 10 to 25% of the mean total body clearance (about 35 ml/min) reported from anuric patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312769 TI - Longitudinal study of cyclosporine and lipids in patients undergoing bone marrow transplantation. AB - The metabolic effects of intravenous cyclosporine on lipids and lipoproteins were studied in 29 allogeneic bone marrow recipients compared with 13 autologous bone marrow patients not requiring cyclosporine therapy. Patients were monitored continuously from 5 days prior to 27 days following transplantation; cyclosporine treatment was initiated 4 days before transplantation. Fasting lipid and lipoprotein levels were measured in serial blood samples throughout the study period. Nutritional supplementation, conditioning regimens and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline between the patient groups. Cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels remained unchanged in autologous patients. As compared with baseline values, plasma total cholesterol increased by an average of 26 percent in allogeneic transplantation patients receiving cyclosporine. Similarly, the ratio of low density lipoprotein to high-density lipoprotein cholesterol was fourfold greater in those patients treated with cyclosporine compared to the autologous group. We conclude that cyclosporine appears to elevate cholesterol levels. Neither acute graft vs host disease nor changes in hepatic function could explain the differences in plasma cholesterol levels between groups. PMID- 2312770 TI - Increased potency of nondepolarizing relaxants after poliomyelitis. AB - The pathophysiology of poliomyelitis and the recognition of the "post-polio syndrome" suggest that susceptibility to muscle relaxants of patients previously affected by this disease, may be altered. We compared the effects of d tubocurarine (dTc), pancuronium (P), and gallamine (G) on two pediatric surgical patient groups: one with a previous history of polio disease, occurring 6 to 12 years prior admission (N = 30, average age: 13 yrs, weight: 43 kg) and another without history of this disease (N = 51, average age: 11 yrs, weight: 39 kg). Following uniform premedication, thiopental, N2O/O2 + narcotic (fentanyl) anesthesia was given for reconstructive surgeries. For orotracheal intubation the patients were briefly paralyzed with 0.7 mg/kg suxamethonium. The thumb adductor responses to supramaximal 1/5 Hz impulses (continuous mode) and to 50 Hz tetanic stimuli (periodically) were recorded. After full recovery from the effect of suxamethonium (100% return of the neurally evoked muscle response) cumulative ED50 values and the recovery index (minutes elapsed from 90% to 50% block of the twitch response) of the three nondepolarizing muscle relaxants were determined. The ED50 of dTc and P were significantly lower with both neuromuscular responses in the post-polio groups (dTc, N = 12 and P, N = 10) as compared to the controls (N = 24 and 18). A tendency toward lower ED50 values in the polio group was also observed with G (N = 6). The differences, however, as compared to the control group (N = 9) were not significant (P less than .2). Recovery times were identical in the polio versus non-polio groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312771 TI - Non-approved indications. PMID- 2312772 TI - Metoprolol CR/ZOK. Proceedings of a workshop. Eze, France, September 7-9, 1989. PMID- 2312773 TI - Effects of a week's beta-adrenoceptor blockade with atenolol and metoprolol CR/ZOK on the response to exercise in healthy women aged 50 to 70 years. AB - 12 healthy women with a mean age of 60 years (range 50-70 years) were treated with 50 mg atenolol or 100 mg metoprolol CR/ZOK or placebo for 1 week in a double blind, randomized, cross-over study. Laboratory measurements of the cardiovascular responses to exercise were made 2-4 hours after and again 24 hours after the last tablet. Blood pressure and heart rate at rest were reduced equally by the two beta-adrenoceptor antagonists. The reductions in blood pressure and heart rate during graded exercise and then during prolonged steady treadmill exercise 3-4 hours after the tablet were greater for atenolol than metoprolol CR/ZOK. The reductions in cardiac output showed a similar pattern. Lactate concentrations and ratings of perceived exertion tended to be highest on metoprolol CR/ZOK, but these differences were inconsistent. We conclude that despite the changes in the cardiovascular system in these 50-70 year-old women, exercise tolerance was not greatly affected by beta-adrenoceptor blockade. PMID- 2312774 TI - Influence of metoprolol CR/ZOK on plasminogen activator inhibitor (PAI-1) in man: a pilot study. AB - Recent primary and secondary preventive trials have shown that long-term metoprolol therapy reduces the risk of acute cardiovascular complications. To test whether part of this beneficial long-term effect may be due to effects on the fibrinolytic system, three pilot studies were performed; two in healthy individuals, and one in patients with mild hypertension or uncomplicated atrial fibrillation. The effect of metoprolol CR/ZOK (controlled release) 100-200 mg daily, on plasminogen activator inhibitor activity (PAI-1) in plasma was measured. In addition serum triglycerides and orosomucoid were analyzed. All the individuals were included in double-blind placebo controlled cross-over trials with treatment periods ranging from 4 days to 3 weeks. During metoprolol therapy PAI-1 values were reduced, while orosomucoid and triglyceride levels were unchanged. A linear inverse correlation was found between fibrinolysis and PAI-1 activity in plasma, indicating that PAI-1 activity serves as an indicator of fibrinolysis. PAI-1 activity and triglycerides were significantly correlated during placebo and metoprolol therapy. In conclusion, our results in these pilot studies suggest that metoprolol enhances fibrinolytic activity as seen by reduced PAI-1 activity. These results should be further confirmed and put into relation of clinical effects of the therapy. PMID- 2312775 TI - Pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK once daily with conventional tablets once daily and in divided doses. AB - Four studies of identical design, each on 18 young healthy subjects, were undertaken to study the pharmacokinetics and beta 1-receptor blockade at steady state after a once daily dose (od) of 100, 200, 300 and 400 mg of metoprolol CR/ZOK (a new controlled release preparation) in comparison with 100 mg dosages (od, bid, tid and qid, respectively) of conventional metoprolol tablets (CT). All studies were of randomized three-way crossover design with 7-day double-blind treatment periods separated by 7-day single-blind washout periods. A number of predose plasma concentrations and assessments of beta 1-blockade were made during the study and a full pharmacokinetic and pharmacodynamic study was performed on day 7. The maximal plasma concentration, Cmax, was significantly lower after metoprolol CR/ZOK compared to CT after all doses--the most pronounced difference being observed after the 100 mg dose when both preparations were given once daily (145 nmol/L vs 606 nmol/L) and the least difference after the 400 mg dose when metoprolol CT was given every 6 hours (837 nmol/L vs 1111 nmol/L). The maximal plasma concentration occurred later after metoprolol CR/ZOK than CT in all studies (median 2.5-4.1 hours vs 1.0-1.2 hours). The trough plasma concentration, Cmin, was significantly higher after 100 mg metoprolol CR/ZOK compared to CT dosed once daily; CminS were comparable between the two preparations in the 200 mg and 300 mg studies and lower after metoprolol CR/ZOK in the 400 mg study (278 nmol/L vs 469 nmol/L). In all four studies the AUCs were significantly lower after metoprolol CR/ZOK compared to CT with the mean relative bioavailability being approximately similar (73-84%). All metoprolol treatments produced a statistically significant beta 1-blockade (measured as percent reduction of exercise induced tachycardia) throughout the whole day compared to placebo except in the 100 mg study where the effect of once daily CT did not differ from placebo during the last 6 hours. Consequently, a significantly higher beta 1-blockade was observed after metoprolol CR/ZOK compared to CT in this latter period. The maximum beta 1-blockade (Emax) after CR/ZOK 100 mg was significantly lower than after CT 100 mg once daily (12.6% vs 23.3%) but when CT was given in divided doses from 200 to 400 mg daily, Emax did not differ between the two formulations. Once daily administration of 100 mg of both products resulted in a significantly higher beta 1-blockade 24 hours after dosing with CR/ZOK compared to CT, but when CT was taken in divided doses this difference between the treatments was less pronounced.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2312776 TI - Pharmacokinetic and pharmacodynamic evaluation of metoprolol controlled release (CR/ZOK) 50 mg in young subjects. AB - In this steady state, cross-over study, the bioavailability and beta 1-blocking effects of metoprolol CR/ZOK 50 mg, conventional metoprolol 50 mg tablets and placebo were evaluated in 12 healthy male subjects (mean age 25 years) after once daily treatment in 5 days. The drugs were administered in a randomized order. The beta 1-blocking effect was defined as percent reduction from baseline in exercise heart rate. The plasma concentration-time profile following metoprolol CR/ZOK 50 mg administration was more even compared to conventional metoprolol tablets, with significantly lower Cmax (mean: 71 vs 221 nmol/L) and significantly higher Cmin (mean: 39 vs 6 nmol/L) for the CR/ZOK formulation. This difference in plasma concentrations was also well reflected by a significantly lower fluctuation index for metoprolol CR/ZOK 50 mg compared with the conventional 50 mg tablet (mean: 69 vs 529%). There was, however, no difference in systemic bioavailability between the two metoprolol formulations (90% confidence limits: 86-106%). The beta 1 blockade was also more even after metoprolol CR/ZOK 50 mg compared to conventional tablets with a significantly lower Emax (mean: 14 vs 19%) and higher Emin (mean: 9 vs 0%) for CR/ZOK. The total effect over a dosage interval, defined as area under the effect curve, was significantly higher for metoprolol CR/ZOK compared to conventional tablets (90% confidence limits: 123-213%). In conclusion, once daily administration of metoprolol CR/ZOK 50 mg to young healthy subjects resulted in smooth plasma concentration and produced a significant beta 1-blocking effect for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312777 TI - A pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK with a conventional slow release preparation. AB - The plasma concentration-time profile and hemodynamic effects of metoprolol after the administration of metoprolol CR/ZOK, a multiple-unit controlled release formulation and a conventional slow release formulation, metoprolol Durules (Astra, AB Hassle, Molndal, Sweden) once daily, were investigated in 12 healthy men. Data were collected over one 24-hour dose interval at steady state after 5 days of treatment. The study was randomized, three-way, crossover double-blind comparison of metoprolol CR/ZOK 200 mg, metoprolol Durules 200 mg and placebo. The reduction in exercise heart rate compared with placebo treatment was used as a measure of beta 1-blockade. The metoprolol plasma concentration-time profile during treatment with metoprolol CR/ZOK was smooth and uniform, showing a more constant release profile than that obtained with metoprolol Durules. This was demonstrated by the significantly longer time period during which the plasma concentration exceeded 75% of the maximum concentration (T75), for metoprolol CR/ZOK compared with metoprolol Durules (P less than .01). The Fluctuation Index of plasma metoprolol concentration was significantly smaller for metoprolol CR/ZOK than for metoprolol Durules (P less than .001). The pharmacokinetic differences between the formulations also produced differences in the time profiles of exercise heart rate. The percentage fluctuation in exercise heart rate over the dose interval tended to be smaller for metoprolol CR/ZOK. At the start and the end of the dosing interval, the CR/ZOK formulation was significantly more effective (P less than .01). These results indicate that Metoprolol CR/ZOK has a more sustained time profile of beta 1-blockade at steady state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312779 TI - Controversy V: phase I, first time in man studies. PMID- 2312778 TI - Pharmacokinetic and pharmacodynamic properties of controlled release (CR/ZOK) metoprolol in healthy Oriental subjects: a comparison with conventional formulations of metoprolol and atenolol. AB - The steady state pharmacokinetics and pharmacodynamics of metoprolol controlled release tablets 100 mg CR/ZOK, was compared with those of metoprolol conventional tablets 100 mg (CT) and atenolol 50 mg (ATL) in ten healthy Oriental men. The study was of double-blind, cross-over placebo controlled design. The three study drugs and placebo were given in a random order once daily for 4 consecutive days with 1-week wash-out between each period. Treadmill exercise tests were performed and blood samples were obtained at fixed intervals after the fourth dose of each treatment. There was less fluctuation in the plasma level-time profile after CR/ZOK than CT and ATL. Plasma concentrations were significantly higher on CR/ZOK than CT at 24 hours after dosing. The relative bioavailability of CR/ZOK to CT was 69.0%. CR/ZOK achieved relatively more uniform beta-blocking effect over the dose interval. Compared to CT and ATL, the peak effect after CR/ZOK was less pronounced and the beta-blockade after 24 hours more effective. PMID- 2312780 TI - Antiarrhythmic drug therapy for suppression of ventricular arrhythmia: experience with 122 patients treated for two years. AB - Although there are many reports of the short-term effectiveness of antiarrhythmic drugs for suppression of ventricular ectopic depolarizations, there are less data available on the long-term use of these drugs. We treated 122 patients for up to 2 years with antiarrhythmic drugs for suppression of frequent ventricular ectopic depolarizations. The percent suppression of ventricular ectopic depolarizations and nonsustained ventricular tachycardia for each drug was determined at 1, 3, 6, 12, 18, and 24 months of therapy. Among 33 patients treated with flecainide, the mean suppression of ventricular ectopic depolarizations (average of all data during 24 months) was 93 +/- 17% and of nonsustained ventricular tachycardia was 97 +/- 7%. In 27 patients treated with encainide, the mean suppression of ventricular ectopic depolarizations was 88 +/- 18% and of ventricular tachycardia was 95 +/- 16%. Among 26 patients treated with propafenone, the mean suppression of ventricular ectopic depolarizations was 77 +/- 32% and of ventricular tachycardia was 93 +/- 15%. For the 20 patients treated with moricizine, the mean suppression of ventricular ectopic depolarizations was 62 +/- 35% and of ventricular tachycardia was 90 +/- 14%. Among 16 patients treated with amiodarone, the mean suppression of ventricular ectopic depolarizations was 92 +/ 14% and of nonsustained ventricular tachycardia was 99 +/- 3%. In 54 of the 122 patients (44%), the study drug was stopped during 2 years of therapy because of death (2 sudden, 2 unwitnessed and 6 noncardiac), side effects (21 patients), lack or of loss of efficacy (13 patients), and noncompliance (10 patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312782 TI - Quinidine does not alter antipyrine metabolism. AB - Quinidine has been reported to be a potent inhibitor of a specific isozyme of cytochrome P-450 (P-450db 1) that is responsible for the metabolism of a select group of drugs. In order to investigate the potential for quinidine to inhibit other isozymes of cytochrome P-450 and to assess whether or not P-450db 1 plays any role in antipyrine metabolism, we studied the effects of quinidine pretreatment on the pharmacokinetics and metabolism of antipyrine in six healthy, male volunteers. Using a randomized, crossover study design with a 2-week washout period between treatments, subjects received a single 1 gram antipyrine dose alone or with quinidine sulfate 200 mg orally every 8 hours for 24 hours prior to the dose of antipyrine and over the 48 hours following antipyrine administration. Mean serum concentrations, apparent oral clearance (1.93 +/- 0.86 vs 2.06 +/- 1.06 L/hr with quinidine) and half-life (13.5 +/- 3.3 vs 12.4 +/- 3.6 hr with quinidine) were not significantly different between the two treatments. The fraction of the administered dose recovered as antipyrine and measured metabolites (56.7% vs 59% with quinidine) as well as the recovery of each individual metabolite was not altered with quinidine pretreatment. In addition, the mean formation clearances for norantipyrine, 4-hydroxyantipyrine and 3 hydroxymethylantipyrine exhibited no change between treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312781 TI - Antihypertensive and metabolic effects of tiapamil. AB - Tiapamil, a new calcium antagonist, was evaluated for its antihypertensive and metabolic effects in a long-term (58 weeks) drug trial in 20 adult outpatient mild to moderately hypertensive subjects. Baseline systolic and diastolic blood pressure dropped after initiation of treatment and was significantly reduced after 4 weeks of treatment, further improving until the termination of the study. There was no impairment of renal and hepatic functions. Electrolytes, plasma aldosterone, plasma renin activity, as well as plasma lipids were not significantly altered during the course of therapy. Fasting blood sugar determinations and oral glucose tolerance test showed significant reductions from the baseline level as a result of the drug treatment. In conclusion, tiapamil is a metabolically safe and effective antihypertensive drug for long-term use. PMID- 2312783 TI - Disposition kinetics of moclobemide, a new MAO-A inhibitor, in subjects with impaired renal function. AB - A single intravenous and oral dose of moclobemide (Ro 11-1163) was administered to 13 subjects with varying degrees of renal impairment (creatinine clearances ranging from 0 to 40 mL/min). The resulting disposition and absorption parameters of moclobemide were more variable than but, with the exception of mean absorption time, were not significantly different from values obtained in another study conducted in 12 normal healthy subjects. There were no relationships between any of the disposition parameters and renal function as measured by creatinine clearance. The disposition of two metabolites of moclobemide were partially characterized from plasma data. One of these (Ro 12-8095) appears to be formation rate-limited and, from available data, behaves in a manner similar to what has been observed in normals. The other metabolite (Ro 12-5637) has a long apparent disposition half-life and is present in greater concentrations in the renally impaired compared to the normal subjects. The latter observation may reflect reduced elimination clearance in the renally impaired subjects. Based upon the results of this study there does not appear to be any need to alter the normal dosing regimen of moclobemide in subjects with renal impairment in order to achieve drug concentrations similar to those in healthy subjects. PMID- 2312784 TI - Anatomical substrates of cholinergic-autonomic regulation in the rat. AB - Acetylcholine (ACh) plays a major role in central autonomic regulation, including the control of arterial blood pressure (AP). Previously unknown neuroanatomic substrates of cholinergic-autonomic control were mapped in this study. Cholinergic perikarya and bouton-like varicosities were localized by an immunocytochemical method employing a monoclonal antiserum against choline acetyltransferase (ChAT), the enzyme synthesizing ACh. In the forebrain, bouton like varicosities and/or perikarya were detected in the septum, bed nucleus of the stria terminalis, amygdala (in particular, autonomic projection areas AP1 and AP2 bordering the central subnucleus), hypothalamus (rostrolateral/innominata transitional area, perifornical, dorsal, incertal, caudolateral, posterior [PHN], subparafascicular, supramammillary and mammillary nuclei). Few or no punctate varicosities were labeled in the paraventricular (PVN) or supraoptic (SON) hypothalamic nuclei. In the mid- and hindbrain, immunoreactive cells and processes were present in the nucleus of Edinger-Westphal, periaqueductal gray, parabrachial complex (PBC), a periceruleal zone avoiding the locus ceruleus (LC), pontine micturition field, pontomedullary raphe, paramedian reticular formation and periventricular gray, A5 area, lateral tegmental field, nucleus tractus solitarii (NTS), nucleus commissuralis, nucleus reticularis rostroventrolateralis (RVL), and the ventral medullary surface (VMS). In the PBC, immunoreactive varicosities identified areas previously unexplored for cholinergic autonomic responsivity (superior, internal, dorsal, and central divisions of the lateral subnucleus, nucleus of Koelliker-Fuse and the medial subnucleus). In the NTS, previously undescribed ChAT-immunolabeled cells and processes were concentrated at intermediate and subpostremal levels and distributed viscerotopically in areas receiving primary cardiopulmonary afferents. In the nucleus RVL, cholinergic perikarya were in proximity to the VMS and medial to adrenergic cell bodies of the C1 area. Punctate varicosities of unknown origin and dendrites extending ventrally from the nucleus ambiguus overlapped the C1 area and immediate surround of RVL. IN CONCLUSION: 1) Cholinergic perikarya and putative terminal fields, overlap structures that are rich in cholinoreceptors and express autonomic, neuroendocrine, or behavioral responsivity to central cholinergic stimulation (PHN, NTS, RVL). The role of ACh in most immunolabeled areas, however, has yet to be determined. Overall, these data support the concept that cholinergic agents act at multiple sites in the CNS and with topographic specificity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2312785 TI - Ultrastructural three-dimensional reconstruction of group III and group IV sensory nerve endings ("free nerve endings") in the knee joint capsule of the cat: evidence for multiple receptive sites. AB - The noncorpuscular endings ("free nerve endings") of thinly myelinated group III and nonmyelinated group IV afferent nerve fibers have been examined in the knee joint capsule of sympathectomized cats by transmission electron microscopy and three-dimensional reconstruction of series of semi- and ultrathin sections. The sensory ending is the most distal part of a group III or IV nerve fiber that consists only of the sensory axon and associated Schwann cells but lacks a myelin sheath and is not surrounded by perineurium. The sensory axon divides into several branches and forms a terminal tree. The branches run either as single fibers or within small Remak bundles in parallel to sensory axons of other endings; they spread along vessel walls and also extend into dense connective tissue. Each sensory axon consists of a series of spindle-shaped thick segments ("beads") connected by waist-like thin segments. Thus all axons of sensory endings have a string-of-beads appearance, which resembles that of efferent sympathetic nerve fibers. The beads of the sensory axon and the end bulb at its tip show the same ultrastructural features which are characteristic of receptive sites: an accumulation of mitochondria and glycogen particles and various vesicles in the axoplasm and "bare" areas of axolemma that are not covered by Schwann cell processes. Group III and group IV sensory endings differ in the length of their branches (up to 200 microM in group III vs. more than 300 microM in group IV), number of beads per 100 microM axon length (about seven vs. nine or ten), mean diameter of axons (0.9-1.5 microM vs. 0.3-0.6 microM), and the presence of a neurofilament core consisting of bundles of parallel microfilaments only in group III. In conclusion, we propose that the sensory part of noncorpuscular "free nerve endings" is formed by the entire terminal tree of group III or group IV nerve fibers and that the beads in the course of the sensory axon represent multiple receptive sites. PMID- 2312786 TI - Variation and symmetry in the lumbar and thoracic dorsal root ganglion cell populations of newly metamorphosed Xenopus laevis. AB - The sizes of the lumbar and thoracic dorsal root ganglion cell populations in normally developing newly metamorphosed Xenopus laevis were measured in order to determine whether these neuron populations have the same characteristics as the hindlimb motoneuron population (i.e., large individual as well as sibling group differences, striking bilateral symmetry, and a rough correspondence between neuron number and body size that suggests some peripheral control of cell number during normal development (Sperry, J. Comp. Neurol. 264:250-267). Among animals from three sibling groups, the total numbers of thoracic and lumbar ganglion cells are highly variable and symmetrical, although symmetry is not uniformly present at the level of individual ganglion pairs. Significant sibling group differences in neuron number are also present. Metamorphic body size and cell number in the thoracic but not in the lumbar ganglia are significantly correlated. The motoneurons innervating the hindlimbs were also counted and measured in the same animals. While variable as well as symmetrical, motoneuron number and metamorphic body size are correlated in only two of the three sibling groups. Interestingly, the numbers of motoneurons and lumbar ganglion cells, two populations of neurons whose sizes one might predict would be significantly correlated in normally developing animals, are not correlated. The relationship between these observations and currently held views concerning how neuron numbers might be controlled during normal development is discussed. PMID- 2312787 TI - Electron microscopic analysis of S-antigen- and serotonin-immunoreactive neural and sensory elements in the photosensory pineal organ of the salmon. AB - Photoreceptor cells in the pineal complex of poikilothermic vertebrates are regarded as homologous with the neuroendocrine pinealocytes in the mammalian pineal organ. They possess an indolamine metabolism, and they contain a number of substances that are immunochemically similar to photo-transduction-related proteins otherwise found in photoreceptors of the lateral eye retina. Using correlative light and electron microscopic pre-embedding immunocytochemistry, we have identified photosensory and neural elements that are immunoreactive with specific antisera against serotonin (5-hydroxy-tryptamine) and the 48 kDa soluble protein S-antigen (arrestin). One type of serotonin-immunoreactive (5HTir) photoreceptor cell was identified. This was characterized by a short basal pole, into which an immunonegative (post-synaptic?) element protruded. Two types of S antigen-immunoreactive (SAir) photoreceptor cells were observed, one characterized by a short basal pole, similar to that of the 5HTir photoreceptors and the other characterized by a long, extensively branching basal pole. In addition, two types of neurons bearing no morphological specializations typical of photoreceptor cells were SAir: bipolar neurons and multipolar neurons. These were often situated dorsally in the pineal organ. The results indicate an emergence of multiple lines of photoreceptor-derived "pinealocytes" either early in phylogeny, or independently in different taxa. The results are discussed in relation to current theories of pineal evolution. PMID- 2312788 TI - Cortical projection patterns of the medial septum-diagonal band complex. AB - A detailed analysis of the cortical projections of the medial septum-diagonal band (MS/DB) complex was carried out by means of anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). The tracer was injected iontophoretically into cell groups of the medial septum (MS) and the vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and sections were processed immunohistochemically for the intra-axonally transported PHA-L. The labeled efferents showed remarkable differences in regional distribution in the cortical mantle dependent on the position of the injection site in the MS/DB complex, revealing a topographic organization of the MS/DB-cortical projection. In brief, the lateral and intermediate aspects of the HDB, also referred to as the magnocellular preoptic area, predominantly project to the olfactory nuclei and the lateral entorhinal cortex. The medial part of the HDB and adjacent caudal (angular) part of the VDB are characterized by widespread, abundant projections to medial mesolimbic, occipital, and lateral entorhinal cortices, olfactory bulb, and dorsal aspects of the subicular and hippocampal areas. Projections from the rostromedial part of the VDB and from the MS are preponderantly aimed at the entire hippocampal and retrohippocampal regions and to a lesser degree at the medial mesolimbic cortex. Furthermore, the MS projections are subject to a clear mediolateral topographic arrangement, such that the lateral MS predominantly projects to the ventral/temporal aspects of the subicular complex and hippocampus and to the medial portion of the entorhinal cortex, whereas more medially located cells in the MS innervate more septal/dorsal parts of the hippocampal and subicular areas and more lateral parts of the entorhinal cortex. PHA-L filled axons have been observed to course through a number of pathways, i.e., the fimbria-fornix system, supracallosal stria, olfactory peduncle, and lateral piriform route (the latter two mainly by the HDB and caudal VDB). Generally, labeled projections were distributed throughout all cortical layers, although clear patterns of lamination were present in several target areas. The richly branching fibers were abundantly provided with both "boutons en passant" and terminal boutons. Both distribution and morphology of the labeled basal forebrain efferents in the prefrontal, cingulate, and occipital cortices closely resemble the distribution and morphology of the cholinergic innervation as revealed by immunohistochemical demonstration of choline acetyltransferase. In contrast, the labeled projections to the olfactory, hippocampal, subicular, and entorhinal areas showed a heterogeneous morphology. Here, the distribution of only the thin varicose projections resembled the distribution of cholinergic fibers. PMID- 2312789 TI - Patterns of tachykinin expression and localization in developing feline neostriatum. AB - The development of tachykinins in the neostriatum was determined qualitatively in order to characterize the ontogeny of an early-forming neostriatal peptidergic system. Tachykinins were detected by immunohistochemistry in fetal, postnatal, and adult cats. Neostriatal cells and neurites expressed tachykinins as early as fetal age 30 and increased in frequency progressively with age. Initial tachykinin expression occurred in neostriatal neurons during their postmitotic migration. In the head of the caudate nucleus, clusters of tachykinin-containing cells and fibers formed between fetal days 35 and 45, when the distribution of labeled neurons changed from a dispersed to an aggregated pattern. Between fetal days 45 and 50, tachykinin-rich neuronal clusters increased in frequency and were distributed throughout the rostral caudate nucleus. In contrast to neurons in clusters, neurons in the complementary neuropil expressed tachykinins largely postnatally. Postnatal morphological maturation of tachykinin-containing neurons paralleled the morphogenesis of medium spiny neostriatal cells. In addition, the caudate nucleus and putamen followed different spatiotemporal gradients of tachykinin expression. These results indicate that tachykinins are expressed in neostriatal neurons during the early ontogeny of the neostriatum and may function as trophic factors before synaptogenesis. PMID- 2312790 TI - Met5-enkephalin-Arg6-Gly7-Leu8-like immunoreactivity in the pelvic ganglion of the male rat: a light and electron microscopic study. AB - By using both light and electron microscopic immunocytochemical methods, Met5 Enkephalin-Arg6-Gly7-Leu8 (MEAGL)-like immunoreactive structures were detected in the pelvic ganglion of male rats. Denervation studies were carried out to determine the origin of these immunoreactive fibers and the projection of immunoreactive neurons within the pelvic ganglion. MEAGL-like immunoreactivity was found in numerous axon boutons, some small, intensely fluorescent (SIF) cells, and a few principal ganglion neurons. Most of the immunoreactive nerve fibers formed pericellular plexuses surrounding the ganglion cells. In addition, there were a few scattered varicose fibers. These fiber plexuses could be classified into two types: type I (approximately 90% of fibers), which consisted of 80-120 small boutons that synapsed on either the dendrites (80% of cases) or somata (20% of cases) of principal neurons; and type II (approximately 10% of fibers), which consisted of 20-40 larger boutons that formed axodendritic synapses exclusively. After transection of the hypogastric and pelvic nerves, virtually all of the pericellular fiber plexuses disappeared, whereas the scattered varicose fibers remained. According to their ultrastructure, these remaining fibers were considered to arise from SIF cells. Following the injection of Fast Blue into the bladder wall, some of the MEAGL-like immunoreactive principal neurons were retrogradely labeled. The results of this study indicate that there are two origins for the MEAGL-like immunoreactive fibers detected in the pelvic ganglion: most arise from preganglionic neurons in the spinal cord, and a small proportion may originate from intraganglionic MEAGL-like immunoreactive SIF cells or principal neurons. Some MEAGL-like immunoreactive principal neurons may project to the urinary bladder. PMID- 2312791 TI - Identification of pedicles of putative blue-sensitive cones in the human retina. AB - Cone photoreceptor pedicles from midperipheral regions of the human retina (6 mm from the foveal center) have been studied by light and electron microscopy. Three areas of cone pedicle mosaic were serially thin-sectioned, in the tangential plane, from the inner border of the outer plexiform layer to the emergence of the cone axons from the cone pedicles. Semithin sections were then collected from the cone axon level through the cone cell bodies to the cone inner segment level. Two hundred twenty-one cone pedicles were followed by this means to their respective inner segments. Eight percent of the cone pedicles were from cones with inner segment characteristics of the blue cones. All 221 cone pedicles were reconstructed by tracing images from electron micrographs. The cone pedicle locations, surface areas, telodendrial projections, and synaptic ribbons could then be measured by morphometry and analyzed by statistical methods. Some selected cone pedicles were reconstructed by computer graphics methods. The cone pedicles identified as belonging to the blue cone type could be distinguished from the surrounding longer wavelength types on the following morphological criteria: 1) they were smaller (50% the area of the surrounding pedicles), 2) they contained shorter synaptic ribbons, 3) they exhibited essentially no telodendrial contact to neighboring cone pedicles, 4) they were positioned slightly more vitread in the outer plexiform layer than neighboring pedicles, and 5) their irregular occurrence in the cone mosaic coincided with the distribution criteria established in our previous paper (Ahnelt et al: J. Comp. Neurol. 255:18 34, '87) for putative blue sensitive cones in midperipheral human retina. PMID- 2312792 TI - Immunohistochemical subpopulations of retinopetal neurons in the nucleus olfactoretinalis in a teleost, the whitespotted greenling (Hexagrammos stelleri). AB - Two subpopulations of retinopetal neurons in the nucleus olfactoretinalis (NOR) were revealed by means of general histological, tract tracing, and immunohistochemical methods in a marine teleost, the whitespotted greenling (Hexagrammos stelleri). Two types of cells in the NOR (M cell, L cell) were morphologically distinguishable from one another. The cell bodies of M cells were medium-size and fusiform, while those of L cells were large and ellipsoidal or irregular. M cells were located at the ventralmost region of the junction between the olfactory bulb and telencephalon, while L cells were scattered more rostrally along the ventromedial surface of the olfactory bulb. Following applications of HRP or Fluoro-Gold to the optic nerve, almost all M cells and about half of the L cells were labeled in the contralateral NOR. L cells showed strong immunoreactivities to gonadotropin releasing hormone (GnRH) and Phe-Met-Arg-Phe NH2 (FMRFamide), whereas M cells showed only weak GnRH-immunoreactivity and no FMRFamide-immunoreactivity. Axons of L cells were detected in the optic nerve by means of GnRH- and FMRFamide-immunohistochemistry. The axons were concentrated in the myelinated edge (the oldest area) of the "ribbon" optic nerve. GnRH- and FMRFamide-immunoreactive fibers constituted a plexus at the junction between the inner nuclear layer and inner plexiform layer. The existence of two structurally separate classes of NOR cells suggests two functionally separate channels from the NOR to the retina. PMID- 2312793 TI - Implantation of cultured sensory neurons and Schwann cells into lesioned neonatal rat spinal cord. I. Methods for preparing implants from dissociated cells. AB - Our goal was to devise methods of implanting defined populations of the cellular constituents of peripheral nerve into regions of spinal cord injury. This objective derived from the knowledge that the cellular environment of peripheral nerve is known to be supportive of axon regeneration from both central and peripheral neurons. Two of the constituents of the peripheral nerve environment known to influence axonal growth are the Schwann cell and extracellular matrix (particularly basal lamina), both of which can be obtained in culture. We describe here large-scale methods of establishing purified populations of rat sensory neurons to which purified populations of Schwann cells were added. These essentially monolayer preparations were then scrolled and cut into lengths of proper shape and size to provide implants for sites of spinal cord injury in newborn rats. We also describe methods enabling the addition of leptomeningeal components to the implants; this addition contributes a proliferating population of vascular endothelial cells (identified by immunostaining) to the otherwise vasculature-free neuron/Schwann cell implant. Light and electron microscopic observations were made to characterize the implants. When the implant was ready for use, it contained Schwann cells that were differentiated, i.e., had begun to ensheathe axons and form basal lamina. The use of a medium containing human plasma to foster endothelial cell growth led to increased neurite fasciculation and Schwann cell migratory activity in the outgrowth, particularly when the neurons and Schwann cells were cultured on leptomeninges. The second paper in this series reports the deportment of these implants and their influence on corticospinal tract growth after placement into regions of dorsal column injury in neonatal rats (Kuhlengel et al., J. Comp. Neurol 293:74-91, 1990). PMID- 2312794 TI - Numbers of neurons and glia in mature rat somatosensory cortex: effects of prenatal exposure to ethanol. AB - Stereological methods were used to examine the consequences of prenatal exposure to ethanol on the structure of area 3, primary somatosensory cortex, of the mature hooded rat. Pregnant rats were fed a liquid diet containing 6.7% (v/v) ethanol (Et), pair-fed an isocaloric liquid control diet (Ct), or fed a diet of chow and water (Ch). Cresyl violet-stained sections of 3-month-old pups were examined. The corrected mean size of the cell bodies of neurons in layers other than layer V was significantly smaller in the Et-treated rats; conversely, the mean somatic size of glia in each layer was significantly larger in the Et treated rats. The laminar cell packing density for neurons and glia, however, was similar in rats from both treatment groups. The overall volume of area 3 and the volume of individual layers were about 33% smaller in Et-treated rats than in the pair-fed controls. Thus, the estimated total number of neurons in Et-treated rats (1.79 X 10(6] was significantly fewer than in Ch-treated rats (2.77 X 10(6] and in Ct-treated rats (2.66 X 10(6]. The total number of glia also was about 30% fewer in Et-treated rats than in the controls. Not all layers were affected equivalently. The space occupied by the neuropil was significantly greater in Et treated rats, but only in layers II/III, IV, and VI; hence, the cell body/neuropil ratio in these layers was less in Et-treated rats than in the controls. Therefore, microcephaly caused by prenatal exposure to ethanol results not only from a miniaturization of the brain, but also from a permanent abnormal organization of cerebral cortex. PMID- 2312795 TI - Toxicity of sumicidin (fenvalerate) to Nubian goats. AB - Deaths in Nubian goats poisoned with oral doses of sumicidin ranging from 112.5 to 1350 mg per kg were preceded by clinical illness in which a variety of signs suggesting central nervous system dysfunction consistently occurred. Hepato-renal changes were present at necropsy in all goats that showed clinical signs. Alterations in serum urea, calcium, inorganic phosphate and cholesterol concentrations and GOT activity were recorded in sumicidin-poisoned goats. PMID- 2312796 TI - Leiomyosarcoma of the duodenum in two horses. AB - Two horses affected by chronic, intermittent colic were found, at post-mortem examination, to have localized annular thickening of a segment of the duodenum. Histological examination of the lesion in both cases revealed a tumour composed of bundles of oval or spindle-shaped cells that stained as muscle with van Gieson stain. The histological diagnosis was leiomyosarcoma. The tumour had caused partial bowel obstruction in both horses. PMID- 2312797 TI - Demonstration of vascular permeability changes in cattle infected with bovine ephemeral fever virus. AB - Five cattle infected with bovine ephemeral fever virus were necropsied on the day after onset of clinical disease, when clinical signs of lameness were most severe. Gross lesions observed included a serofibrinous polyserositis involving the synovial, pericardial, thoracic and abdominal cavities. The associated histological changes consisted primarily of oedema and an influx of neutrophils into affected tissues and fluids. In a further eight infected cattle, increases in permeability of vessels associated with serosal surfaces were demonstrated by labelling with either colloidal carbon or Evans blue. Intravenous injections of carbon provided both macroscopic and histological labelling of affected vessels. Evans blue appeared to be more sensitive than carbon but did not provide a histological marker of vascular permeability and provided labelling of tissues rather than individual vessels. The main sites of increased permeability were synovial, pericardial, thoracic and abdominal serosae. PMID- 2312798 TI - Gastric leiomyomas in the Japanese newt, Cynops pyrrhogaster; ultrastructural observations. AB - Nineteen of 700 outwardly healthy captive adult Japanese newts, Cynops pyrrhogaster, had nodular neoplasms protruding on the gastric serosal surface. These tumours were characterized as sharply circumscribed leiomyomas of the muscularis externa with occasional submucosal involvement. Ultrastructural analysis of tumour myocytes revealed irregular-shaped, well-differentiated cells with cytoplasmic processes, and reduced quantities of intracellular myofibrils. They were surrounded by enlarged intercellular spaces filled with disorganized and increased amounts of collagen. Vacuolation was seen both in tumour myocytes and in mucous epithelial cells. Virus-like particles were observed in nuclei of some tumour myocytes. Interstitial cells with laminated-type granules were seen amongst tumour cells. These relatively benign leiomyomas shared some morphologic features with human gastric leiomyomas. Their cause and prognosis remain unknown. PMID- 2312799 TI - The ovine immune response to Chlamydia psittaci; histopathology of the lymph node. AB - The histopathological response of the ovine popliteal lymph node to infection by an ovine abortion strain of Chlamydia psittaci was studied. After infection of 10 seronegative sheep by the subcutaneous route, the draining popliteal lymph nodes enlarged considerably. By day 6, expansion was more marked in the medulla than in the cortex but, by day 18, cortical follicles were prominent. Immunoglobulin containing cells increased in number both in the medulla and cortex between days 6 and 18. C. psittaci was re-isolated from three nodes on day 6 and one on day 12, but at no stage was it demonstrated in tissue sections by an immunoperoxidase method. Thus it was shown that while C. psittaci could apparently become "latent" in lymphoid tissue, it could also stimulate a profound response at the same site. PMID- 2312801 TI - Suicidal ideation in Darier's disease. AB - We investigated the psychiatric history of patients with severe Darier's disease and a control group, which consisted of patients with comparably severe dermatologic disorders of keratinization. Three patients with Darier's disease reported either a suicide attempt (one patient) or a specific suicide plan (two), compared with one patient in the control group. Of 11 patients with Darier's disease, 7 had a history of suicidal thoughts, compared with 3 of 11 patients in the control group. Thus suicidal ideation is a potential problem in patients with cutaneous illnesses, particularly those with chronic disfiguring disorders such as severe Darier's disease. PMID- 2312800 TI - Immunological malfunctions associated with low selenium-vitamin E diets in lambs. AB - Lymphoproliferative responses to phytohaemagglutinin and other phytolectins declined following prolonged exposure of lambs to a diet deficient in both selenium and vitamin E, coinciding with the development of nutritional myopathy. Supplementation restored lymphocyte responses within a week and led to a rapid decline in circulating activity of the muscle enzyme creatine kinase in serum. Lymphocyte responses of the dams remained largely unaltered throughout the experiment. There was no evidence of erythrocyte damage in myopathic lambs, concentrations of serum IgG, IgM and lysozyme were similar to those in healthy lambs, and chemiluminescence tests on whole blood samples failed to reveal a phagocytic defect in response to particulate and non-particulate stimuli. However, serum from myopathic lambs did show a reduced opsonic capacity. PMID- 2312802 TI - Mid dermal elastolysis. AB - Mid dermal elastolysis is an exceedingly rare condition. Only three cases have been reported previously. The disease manifests as sharply marginated plaques of fine wrinkles of various size that give the skin an aged appearance. It is characterized histologically by a complete absence of mid dermal elastic fibers and lack of any inflammatory infiltrate. Two new cases are reported, and the other cases are reported. PMID- 2312803 TI - The effect of vitiligo on sexual relationships. AB - To study the effect of vitiligo on interference with sexual relationships, we surveyed 158 patients by questionnaire. Although a majority of patients reported a negative impact on sexual relationships, most patients felt embarrassment when showing their body or meeting strangers. The majority of patients who reported a negative impact on sexual relationships attributed the problems to their embarrassment. Those who were particularly affected were those with low self esteem, men, those to whom appearance is important, and single persons. Dermatologists should be especially alert to the effects of disfigurement and should attempt to assist patients with this problem. PMID- 2312804 TI - A new strategy of iontophoresis for hyperhidrosis. AB - We used a modified iontophoretic method with an anticholinergic agent and aluminum chloride to treat hyperhidrosis. The strategy behind this combination was to shift gradually from inhibition of sweat gland secretion to blockage of the sweat duct. In a double-blind study in which we compared our method with tap water iontophoresis, the results were comparable. A second study revealed an 87% response rate, with an average remission period of 32 days. Our data indicate that patients who were older at onset, had a family history negative for the disorder, had an early response, or underwent treatment in cool weather had the most favorable results. PMID- 2312805 TI - Topical cyclosporine in male pattern alopecia. AB - We previously demonstrated a systemic and topical effect of cyclosporine on hair growth in an experimental model composed of human scalp skin transplanted onto nude mice. The aim of this study was to determine whether topical cyclosporine affects male pattern alopecia. For 4 months in a double-blind study, 10 subjects were treated with cyclosporine and three were treated with olive oil. Hair growth was evaluated by photographs and hair counts. Significant hair growth was observed in two of the eight patients who completed the study. In one the hair growth was cosmetically satisfactory. No systemic or cutaneous side effects were noted. PMID- 2312807 TI - Histologic atypia in clinically benign nevi. A prospective study. AB - Histologic features of dysplastic nevi include varying degrees of pattern atypia, cytologic atypia, and host response. The purpose of this prospective study was to determine the prevalence of these histologic features in benign acquired nevi. Fifty-eight junctional and compound nevi from 26 volunteer subjects were excised and examined. All nevi met each of the following criteria: 5 mm or less in diameter, symmetric, round or slightly oval, uniform pigmentation, distinct and regular margins, and no erythema. One or more of the histologic features associated with dysplastic nevi were present in 87.8% of the lesions; two or more were present in 69%; and all three histologic features were found in 29.3%. These results indicate that histologic features of dysplastic nevi occur in benign common acquired nevi. PMID- 2312806 TI - Melanoma in children. AB - Four cases of malignant melanoma in children younger than 17 years of age are presented. Several preexisting conditions increase the risk of development of melanoma during childhood. These include giant congenital melanocytic nevi, the familial dysplastic nevus syndrome, and xeroderma pigmentosum. The role of small congenital lesions and sporadic dysplastic nevi in the development of melanoma in children is less clear. The signs and symptoms associated with melanoma in children are similar to those in adults, as are the histopathologic features, biologic behavior, and treatment of this tumor. The inadequacy of available therapy for metastatic melanoma underscores the necessity for the early diagnosis and prompt surgical treatment of melanomas in children. PMID- 2312809 TI - Ethics and the academic-corporate relationship. PMID- 2312810 TI - Reducing melanoma mortality: the magnificent obsession. PMID- 2312811 TI - DNA repair mechanisms and their biologic implications in mammalian cells. Report of a NATO advanced research workshop, Fontevraud, France, Oct. 2-7, 1988. PMID- 2312808 TI - Immediate intraoperative tissue expansion. AB - We report a modification of the controlled tissue expansion technique, that is, immediate intraoperative tissue expansion. The procedure is performed by placing tissue expanders at the time of surgery. After placement, three to four cycles of inflation/deflation of the expander for 3 to 5 minutes are performed. In a one stage procedure the stretched skin is then immediately used to close the surgical defect. Three case reports demonstrating the immediate intraoperative tissue expansion technique, in which the Foley catheter balloon was used as the tissue expander, are presented. These cases illustrate that this technique may allow the surgeon to cover defects more easily with less tension and with a better cosmetic result than with other closure techniques. PMID- 2312813 TI - Juvenile dermatomyositis treated with cyclosporine. PMID- 2312812 TI - Salon care product labeling. PMID- 2312814 TI - Fumaric acid therapy for psoriasis: a randomized, double-blind, placebo controlled study. PMID- 2312815 TI - Pimozide in delusions of parasitosis. PMID- 2312816 TI - Acquired secondary syphilis in a child. PMID- 2312817 TI - Discoid lupus erythematosus scarring and dermabrasion: a case report and discussion. PMID- 2312818 TI - Cutaneous oxalate granuloma. PMID- 2312820 TI - Epidermal nevi and the epidermal nevus syndrome. PMID- 2312819 TI - A safe and effective modification of the hot-quartz mercury-vapor light source for routine office-based phototesting. PMID- 2312821 TI - Response to Alegre and Winkelmann: Sneddon's syndrome. PMID- 2312822 TI - Ulcerated edematous limb and transcutaneous oxygen tension. PMID- 2312823 TI - Transcutaneous measurement of oxygen tension. PMID- 2312824 TI - Actinic lichen planus: treatment with antimalarials. PMID- 2312825 TI - Laryngeal involvement in dermatitis herpetiformis. PMID- 2312826 TI - Effects of intravenous gamma-globulin in pemphigus. PMID- 2312827 TI - Basal cell carcinoma. A population-based incidence study in Rochester, Minnesota. AB - Population-based annual incidence rates for histologically proved basal cell carcinoma were derived from the records linkage system of the Rochester Epidemiology Program Project. Residents of Rochester, Minnesota, during the years 1976 to 1984, formed the observational cohort. A total of 657 first episodes of basal cell carcinoma were observed. Annual incidence rates per 100,000 persons in the Rochester population, standardized to the 1980 U.S. white population, were 175 for men, 124 for women, and 146 combined. Recurrent or subsequent basal cell carcinoma was observed among 30% of patients during an average of 4.5 years of follow-up; no metastatic lesions occurred. The rates of recurrence were similar after complete excision or treatment with curettage and cauterization in these observational data. PMID- 2312828 TI - Malignant melanoma of the female genitalia. AB - Fifteen women with genital malignant melanoma were studied. Their ages ranged from 19 to 66 years (mean 49.1 years); 12 were white, and three were black. The sites of involvement were the mons pubis (one patient), perineal body (one), labium majus (three), labium minus (three), and vagina (seven). Ten patients (66.6%) died of their disease, one is alive with disease, and four are alive without evidence of disease. For the living patients the duration of follow-up was 20 to 118 months (mean 63.6 months). Of those who died, survival ranged from 3 to 76 months (mean 25.1 months). The predominant type of malignancy was superficial spreading melanoma 50%. Nodular melanoma represented 22%, and the nodular polypoidal variant 14%. Melanoma of the squamous mucosa, also referred to as lentiginous melanoma, constituted 14%. By using Chung's method of determining levels of invasion, we found that no lesion was in situ (level I), two were level II (less than 1.0 mm thick), one was level III (between 1.0 and 2.0 mm) and the remaining 11 patients had lesions that were greater than 2.0 mm (levels IV and V). Because the subcutaneous fat is not consistently present in all sites of the female genitalia, all tumors thicker than 2.0 mm were included in level IV, and no level V tumors were classified in our study. Using Breslow's microstaging method, we found the thickness to range from 0.65 to 9.5 mm (mean 4.75 mm). When we correlated survival with level and thickness of tumor in nine patients who died, one tumor was level III and eight were level IV; thickness ranged from 1.65 to 9.0 mm (mean 5.64 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312829 TI - Dermatitis herpetiformis in two American blacks: HLA type and clinical characteristics. AB - Dermatitis herpetiformis is a rare blistering skin disease characterized in part by granular IgA deposits at the dermoepidermal junction, an associated gluten sensitive enteropathy, and a strong association with the human histocompatibility leukocyte antigen (HLA)-A1 (74% of patients with dermatitis herpetiformis), -B8 (88%), -DR3 (95%), and -DQw2 (100%). Dermatitis herpetiformis is rarely seen in American blacks and some investigators have postulated that this finding may be due to the decreased frequency of HLA-A1 and -B8 in American blacks compared with Caucasians (American blacks: HLA-A1 = 15.3%, HLA-B8 = 10.7%; Caucasian: HLA-A1 = 26.4%, HLA-B8 = 18.3%). This report describes two American blacks with dermatitis herpetiformis and reports the results of HLA typing of these subjects for HLA-A, B, -C, -DR, and -DQ antigens. HLA typing revealed that neither patient expressed HLA-A1 or -B8; however, both patients did express the class II antigens most frequently seen in dermatitis herpetiformis, HLA-DR3 and -DQw2. Comparison of HLA class II antigen frequency in normal American blacks and Caucasians reveals a similar frequency of HLA-DR3 and -DQw2 (American blacks: HLA-DR3 = 27.6%, HLA DQw2 = 40.9%; Caucasian: HLA-DR3 = 22.6%, HLA-DQw2 = 32.9%). These data confirm the importance of the HLA class II region in the pathogenesis of dermatitis herpetiformis. In addition, these data suggest that the rare occurrence of dermatitis herpetiformis in American blacks is not due to the decreased frequency of the HLA class I antigens -A1 and/or -B8 but rather is related to differences in the HLA class II region not detected by routine HLA typing. PMID- 2312830 TI - Sarcoidosis of the upper respiratory tract in patients with nasal rim lesions: a pilot study. AB - Lupus pernio has been associated with sarcoidosis of the upper respiratory tract. The semantic differences in the use of the designation "lupus pernio" are such that American dermatologists may not consider patients with nasal rim papules of sarcoidosis to have lupus pernio. During a 12-month period, we referred each new patient with sarcoidosis and nasal rim lesions for direct and indirect laryngoscopy. Three of our four patients had sarcoidosis of the upper respiratory tract. We recommend a large prospective study to assess the incidence of this disorder in patients with nasal rim lesions of sarcoidosis. Until such a study is undertaken, however, we believe that consideration should be given to otolaryngologic examination of these patients, regardless of their symptoms. PMID- 2312831 TI - The photoprotective potential of the new superpotent sunscreens. AB - A sun protection factor (SPF)-15 and an SPF-30 sunscreen were compared with regard to their ability to prevent sunburn cell formation after the exposure of human skin to a standardized dose of solar-simulated radiation. The SPF-30 sunscreen provided a significantly superior degree of photoprotection and almost prevented sunburn cell induction. Because sunburn cells may be markers of ultraviolet radiation-induced damage to DNA, the new superpotent sunscreens should offer an advantage in the prevention of skin cancer and long-term actinic damage to skin. PMID- 2312832 TI - Genital lentiginosis: a clinical and histopathologic study. AB - We studied the clinical and histopathologic characteristics of melanotic macules of the penis and vulva. The 10 lesions studied were relatively large (up to 2 cm), multifocal, irregular in outline, and had variegated pigmentation. Most were regarded as clinically atypical in appearance. Histologic examination of the lesions showed basal layer hyperpigmentation, slight melanocytic hyperplasia, epithelial hyperplasia, and stromal melanophages. No cytologic atypia of melanocytes was detectable. Information is insufficient at present to predict the natural history of genital lentiginosis or its relation to mucocutaneous melanoma. PMID- 2312834 TI - Factor XIII expression in the skin: observations and a hypothesis. AB - Factor XIII, a transglutaminase whose best-known function is in the coagulation cascade, is widely distributed in tissues. Three patterns of expression are found in the skin: (1) in cells in an angiocentric pattern around superficial vessels, (2) in early reparative lesions that result in fibroplasia, and (3) in certain sessile neoplasms. Around superficial vessels factor XIII probably stabilizes fibrin clots and helps to seal superficial wounds. On the basis of patterns of expression in evolving reparative lesions, factor XIII likely has an important but still undefined function in the development of fibroplasia. Factor XIII's proposed role in the promulgation of fibroplasia would be integral to the production of the stromal component of small neoplasms that is known to be associated with factor XIII expression. PMID- 2312833 TI - Septal granulomatous panniculitis: comparison of the pathology of erythema nodosum migrans (migratory panniculitis) and chronic erythema nodosum. AB - Fifty-eight cases of septal granulomatous panniculitis were reviewed; 14 cases were diagnosed as erythema nodosum migrans (migratory panniculitis) and 36 as chronic erythema nodosum on the basis of clinical and histopathologic features. Erythema nodosum migrans was characterized by markedly thickened and fibrotic septae, marked capillary proliferation (like granulation tissue), and massive granulomatous reaction (with giant cells) along the borders of the widened septa. Hemorrhage was rare, and phlebitis was not seen. Chronic erythema nodosum showed mild septal change, little fibrosis, and lymphohistiocytic perivascular inflammation with only focal granulomatous formation. Phlebitis and hemorrhage were common. The condition termed erythema nodosum migrans has many of the same clinical features as chronic erythema nodosum, and we think this term is preferable to migratory panniculitis. We believe that there are sufficient clinical and histopathologic features to justify considering erythema nodosum migrans as a unique clinicopathologic entity. PMID- 2312835 TI - Dermatology and the environment: a unique opportunity. PMID- 2312836 TI - Methotrexate: anti-inflammatory or antiproliferative? PMID- 2312837 TI - The melanocyte: an essential link in hydroquinone-induced ochronosis. PMID- 2312838 TI - 'Sebaceoma' associated with centroblastic-centrocytic lymphoma. PMID- 2312840 TI - Infrared radiation. PMID- 2312839 TI - Clearing of epidermolysis bullosa acquisita with cyclosporine. PMID- 2312841 TI - Detection of coronary artery disease using MR imaging with dipyridamole infusion. AB - Exercise testing in the magnetic resonance (MR) scanner is difficult because of space restriction and movement artefact, which limit its use in the investigation of patients with suspected coronary artery disease. Pharmacological stress, however, can be used as a substitute for exercise. Therefore, a patient with angina underwent MR ventricular wall motion studies before and after intravenous dipyridamole. Reversible abnormal regional contraction of the myocardium was demonstrated and correlated with a reversible perfusion defect on subsequent thallium myocardial perfusion imaging and a blocked artery at coronary angiography. A clinically useful investigative procedure may be developed. PMID- 2312842 TI - MR imaging in the definition of coronary artery anomalies. AB - Coronary angiography remains the standard imaging technique to study coronary artery anatomy. Coronary artery aneurysms and fistulas are often incompletely visualized with routine angiography. Magnetic resonance (MR) imaging of such coronary anomalies is presented. The MR images improve the preoperative assessment of patients with coronary artery aneurysms and fistulas. PMID- 2312844 TI - MR imaging in pediatric airway obstruction. AB - Magnetic resonance (MR) imaging of the trachea was performed in 27 children with congenital tracheal narrowing. The diagnoses included aortic arch anomalies (n = 7), innominate artery compression (n = 13), pulmonary artery compression (n = 5), and tracheomalacia (n = 2). Demonstration of the trachea and the surrounding tissue and vessels on MR images allowed the evaluation of the cause of tracheal compression and the degree and location of collapse. Patients were examined with MR imaging if the cause of airway obstruction was still unclear after bronchoscopy. It is concluded that MR imaging is a well suited modality for characterizing tracheal narrowing without using ionizing radiation or intravenous contrast medium. PMID- 2312843 TI - Tracheobronchial mucociliary clearance and alveolar epithelial permeability measured by PET with 18FDG powder. AB - Tracheobronchial mucociliary clearance and alveolar permeability were measured with positron emission tomography using a water-soluble dry aerosol, sodium-N acetyl-neuraminate tagged with 2-deoxy-2-[18F]fluoro-D-glucose (18FDG powder). Five normal volunteers inhaled 1.5-2.0 mCi of FDG powder by a single deep breath. The distribution of radioactivity, measured by scanning during a period of 120 min, showed that the 18FDG powder deposition progressed from the central airways to the peripheral alveolar areas. In the tracheobronchial system the radioactivity decreased to 24% of the initial deposition at 60 min. In the peripheral alveolar area, where absorption into blood or lymphatic flow crossing the epithelial layer represents a unique mechanism of clearance for water-soluble 18FDG powder, alveolar radioactivity decreased slowly to approximately 70% of the initial deposition at 60 min after inhalation. Positron emission tomography using 18FDG powder provides a regional evaluation of both mucociliary transport in the tracheobronchial system and epithelial permeability in the alveolar area. PMID- 2312845 TI - MR imaging of unilateral pulmonary artery anomalies. AB - Magnetic resonance (MR) imaging of the pulmonary arteries was performed in seven children with unilateral pulmonary artery abnormalities. Five had congenital absence or interruption of a pulmonary artery; two had postsurgical occlusion or narrowing of a pulmonary artery. A small patent hilar pulmonary artery was identified in one of the five cases of congenital pulmonary artery interruption or absence. Occluding thrombus was identified in the right pulmonary artery of one child following pulmonary artery banding. In another case marked narrowing of the right pulmonary artery was identified secondary to migration of a pulmonary artery band. The MR findings were confirmed by angiography in all cases. Magnetic resonance appears to be a useful noninvasive modality for accurate anatomic depiction of unilateral pulmonary artery abnormalities in childhood. It may be especially valuable for diagnosis of pulmonary artery stenosis or occlusion following surgical treatment of congenital heart disease. PMID- 2312846 TI - MR imaging of pleural effusions. AB - To investigate the in vivo magnetic resonance (MR) characteristics of pleural effusions, MR imaging was performed on 22 patients who also underwent thoracentesis. Correlation of the MR scans with results of thoracentesis revealed significant differences among three types of effusions: transudates (T) (n = 4), simple exudates (SE) (n = 9), which did not have malignant cells or infection, and complex exudates (CE) (n = 9), which did have malignant cells or infection. Using normalized MR intensities, CE were more intense than SE, which were brighter than T. The second and third echoes (TE 66 and 99 ms) provided the best differentiation for these three classes of effusions, with p less than 0.06 and p less than 0.006, respectively. Qualitative visual assessment of the increase in signal intensity was also useful in differentiating among the three types of effusions (p less than 0.02). Effective T2 values (normalized to fat) were significantly shorter for exudates than for T (p less than 0.02). Heterogeneity, loculation, and size of effusions were well evaluated on MR. Magnetic resonance is not specific for the etiology of effusions. Nevertheless, with analysis of both quantitative and qualitative parameters, MR may provide an effective noninvasive means for the initial characterization and serial follow-up of pleural effusions. PMID- 2312847 TI - Distinction of hepatic vein from portal vein by MR imaging. AB - Fast magnetic resonance (MR) imaging techniques are assuming importance in imaging of the abdomen in part due to their ability to produce images during breath-holding, which ensures high spatial resolution and no respiratory motion artifacts. One problem with rapid scanning of the liver, shared with other MR techniques, is confusion between portal and hepatic veins due to similarity in signal intensity. The fast low angle shot (FLASH) technique (flip angle 40 degrees, repetition time 28 ms, and echo time 16 ms) produces high signal in both venous systems. To remedy the problem we incorporated presaturation pulses applied across the portal and mesenteric veins to the FLASH technique; this induced a decrease in signal in the portal venous system and facilitated their differentiation from hepatic veins. Moreover, in one patient an intraportal tumor thrombus not detected on the standard FLASH technique was rendered visible by presaturation. Although the presaturation pulses in the present series were confined to the sagittal plane, the technique should be applicable in any plane as dictated by the anatomy and direction of blood flow. We anticipate wide use of combined presaturation and rapid scanning techniques. PMID- 2312850 TI - Cavernous hemangioma of the liver: assessment of MR tissue specificity with a simplified T2 index. AB - This is a comparison of the ability of two quantitative magnetic resonance (MR) indices: (a) the second echo signal drop (SESD) (a simplified index of T2 relaxation times that we have developed); and (b) the previously described lesion/liver signal intensity ratio (LLR) to provide histologic diagnosis in hepatic lesions greater than 2 cm in diameter. In 55 patients 108 hepatic masses [31 cavernous hemangiomas (CH), 68 metastases, and 9 hepatocellular carcinomas] were scanned at 0.5 T. Statistically significant differences between CH and malignant lesions were obtained in mean SESD (p = 0.0006) and LLR (p = 0.0008) using repetition time (TR) 2,100/echo time (TE) 35, 60 ms. Application of cutoff values derived from receiver-operator characteristic analysis led to a correct diagnosis in 100 and 94% of lesions, respectively. Using TR 2,100/TE 35, 90 ms in a different patient population, CH and malignancies again displayed significantly different mean values, using the SESD (p = 0.0090) and LLR (p = 0.0024) methods. These measurements provided a correct diagnosis in 74 and 81%, respectively. Accuracy was increased in those cases in which the diagnosis by SESD and LLR were concordant. When compared with visual analysis, these quantitative methods appear to achieve near 100% accuracy in the differentiation of hepatic CH from malignancies. PMID- 2312848 TI - Differentiation of hepatic hemangiomas from metastases by dynamic contrast enhanced MR imaging. AB - Twenty-nine patients with hepatic hemangiomas (n = 14) and hepatic metastases (n = 15) underwent magnetic resonance (MR) imaging prior to and after an intravenous bolus injection of Gd-diethylenetriamine pentaacetic acid (0.2 mmol/kg). Before contrast application, a T2-weighted spin echo sequence (SE 1,600/105) and a T1 weighted gradient echo sequence (GE 315/14/90 degrees pulse angle) were performed. Beginning with injection of the contrast agent, a dynamic study was conducted for 10 min using a moderately T1-weighted gradient echo sequence (GE 40/14/40 degrees) with an acquisition time of 10.2 s per image. Delayed (11 min) and late (60 min) postcontrast images were obtained using a T1-weighted sequence (GE 315/14/90 degrees). In the dynamic study (0-10 min) the hemangiomas were characterized by peripheral contrast enhancement and a subsequent hyperintense fill-in. The metastases showed very mixed patterns of enhancement after contrast administration, and their signal intensity remained low compared with that of the hepatic tissue. In the delayed postcontrast examination (11 min) the hemangiomas had a very high and homogeneous signal intensity and the metastases were characterized by an inhomogeneous, hypointense to isointense signal. The contrast between tumor and liver [signal-difference-to-noise ratio (SD/N)] was higher for all hemangiomas than it was for the metastases. In the T2-weighted precontrast examination, on the other hand, five hemangiomas and seven metastases showed an overlap in the SD/N. The late postcontrast images (60 min) did not yield any further diagnostic information. We conclude that the combination of a dynamic MR study with delayed postcontrast T1-weighted imaging is a useful method of diagnosing hepatic hemangiomas. PMID- 2312849 TI - Gadolinium-DOTA enhanced fast imaging of liver tumors at 1.5 T. AB - Twenty patients [15 men, 5 women, 19-71 years old (mean 52 years)] highly suspected of having tumoral liver pathology were prospectively studied with motion compensated T2-weighted spin echo (SE) [repetition time (TR) 2,200 ms, echo time (TE) 90 ms] and Gd-DOTA enhanced gradient echo fast low angle shot [TR 60 ms, TE 10 ms, angle 30 degrees) sequences. The final diagnoses were hemangioma (five), hepatocellular carcinoma (four), focal nodular hyperplasia (one), adenoma (one), metastasis (two), abscess (two), echinococcal cyst (one), tumor of unknown origin (three), cirrhosis (one). Contrast enhanced images were obtained during the early vascular phases after intravenous bolus injection of Gd-DOTA at a dose of 0.1 mmol/kg (0.2 ml/kg). After Gd-DOTA, positive contrast enhancement was seen in 11 cases, negative enhancement in 4, and nonenhancement in 6. Contrast patterns were similar to contrast enhanced CT. In terms of visibility of lesions, the unenhanced motion-compensated T2 SE sequences were superior to the nonenhanced gradient echo sequences in 12 patients and equal in 8. After gadolinium enhancement, T2-weighted SE images were superior to the postcontrast gradient echo images in eight cases, equal in eight and inferior in four cases. PMID- 2312851 TI - Replacement lipomatosis of the kidney: CT features. AB - Replacement lipomatosis of the kidney is a severe loss of renal parenchyma with massive fat deposition associated with long-standing inflammation and calculi. We report two pathologically proven cases of total replacement lipomatosis and one partial replacement lipomatosis diagnosed by CT. The CT images demonstrated a large fat-attenuating mass with perirenal capsule surrounded by thick pararenal fascia, streaky densities in the mass, elongated collecting system, large calculi, and absence of renal parenchyma. PMID- 2312852 TI - CT diagnosis of catheter-induced septic thrombus of vena cava. AB - Two cases of septic thrombosis of the vena cava induced by central venous catheterization are reported. Computed tomography showed thrombi containing gas bubbles in the venae cavae; one involving the superior vena cava and the other the left-sided inferior vena cava. Computed tomography also demonstrated surrounding inflammatory infiltrations in the upper mediastinum or retroperitoneum. PMID- 2312854 TI - MR imaging of spinal neurinomas with pathological correlation. AB - Eight patients with nine spinal neurinomas were examined with magnetic resonance (MR) imaging. We attempted to correlate MR images with the gross and microscopic characteristics of the tumors. On T1-weighted images (T1WIs) all tumors were iso- to slightly hyperintense to CSF, although two comprised hyperintense areas. On the T2-weighted pulse images (T2WIs), available for seven tumors, two tumors were markedly and two relatively hyperintense to CSF. Three tumors exhibited mixed signal intensity. On macroscopic examination, the markedly hyperintense areas on T2WIs corresponded to the cystic portions and relatively hyperintense areas to the solid portions. Areas that were hypointense on T2WIs and isointense or markedly hyperintense on T1WIs corresponded to hemorrhage. On microscopic examination it was impossible to establish a correlation between Antoni A and Antoni B tissue types and features recognized on T1WIs and T2WIs. Gadolinium diethylenetriamine pentaacetic acid enhanced T1WIs were performed in four patients with five tumors. All tumors enhanced, demonstrating the tumor contours and the cystic degeneration within. PMID- 2312853 TI - MR imaging of foraminal and extraforaminal lumbar disk herniations. AB - Foraminal and extraforaminal disk herniations are less frequent than intraspinal herniations at the lumbar level and more difficult to diagnose. They are undetected by myelography and distinction between them and an enlarged nerve root may be difficult with CT. Thirty-three patients presenting with persistent radiculopathy and showing an image suggesting a far lateral disk herniation on CT at 34 disk levels were prospectively imaged with magnetic resonance (MR). In all cases the disk fragment was identified and its separation from the nerve root was possible. This separation was more readily visible on sagittal or angled coronal views. The exact location of the herniation in relation to the facet joints and the pedicles was best assessed with MR: Ten were purely intraforaminal, 8 extraforaminal, and 15 both. Cephalad migration was noted on the sagittal lateral facet plane in 71% of cases. Surgical correlations were available for 25 disks. Three were falsely positive for disk herniation. Enlarged foraminal veins were responsible for this appearance as confirmed by surgery in two of these. When a prediction of disruption of the lateral extension of the posterior longitudinal ligament was made, it was confirmed at surgery in 52% of cases because of extreme lateralization of the herniations. PMID- 2312855 TI - Leptomeningeal metastases: MR evaluation. AB - Forty patients with positive CSF cytology for subarachnoid dissemination of neoplasms were examined by magnetic resonance (MR) imaging for the detection of intracranial or intraspinal CSF metastases. The MR evidence of cerebral leptomeningeal metastases was noted in 12 of 54 unenhanced (22.2%) and 7 of 20 (35%) gadolinium-enhanced studies. However, in only 2 of the 20 (10%) gadolinium enhanced scans did the enhanced brain images alone demonstrate the presence of CSF seeding. Four of 29 (13.8%) unenhanced studies of the spine and 6 of 16 (37.5%) gadolinium-enhanced spine studies were positive for neoplastic deposits on the spinal nerves or cord. Magnetic resonance without and with gadolinium enhancement was most likely to be positive in studies of patients with a non-CNS primary malignancy (16/51 = 31.4%) and least accurate with lymphoma or leukemia (1/18 = 5.6%). Although gadolinium administration increases the ability of MR to detect leptomeningeal metastases (particularly in the spine), the overall sensitivity of unenhanced and enhanced MR examinations is low (19.3 and 36.1%, respectively) in patients with proven cytological evidence of neoplastic seeding. PMID- 2312856 TI - Cortical blindness during chemotherapy: clinical, CT, and MR correlations. AB - Two patients treated by chemotherapy for a non-Hodgkin malignant lymphoma developed focal neurological symptoms including disorientation, hemoplegia, and cortical blindness 5 and 15 days after the end of a polychemotherapy course, including methotrexate and vindesine. In both patients ECG and blood pressure were normal. Case 1 had a slight increase of protein level without cells on CSF examination and presented with a paralytic ileus. Case 2 developed an inappropriate antidiuretic hormone secretion (IADHS) syndrome. In both cases, noncontrast CT scans showed bilateral, symmetrical low density areas within the temporooccipital regions. Postcontrast CT images stressed major cortical and subcortical enhancement predominantly over the gray matter. In Case 2 the lesions also affected the right parietal lobe. Magnetic resonance scans 2-3 weeks after the onset of neurological symptoms demonstrated low intensity signal lesions on T1-weighted images and bright signal on T2-weighted images. In Case 1 the visual deficit failed to regress and in Case 2 the patient died 2 months later because of the natural evolution of her lymphoma. The clinical and radiological data suggested that a vascular ischemic process was responsible for the cerebral lesions in these two patients. As Vinca alkaloids and not methotrexate have been implicated as a cause of cortical blindness, and as our two patients presented signs of overdose of vindesine (paralytic ileus and IADHS), we suggest that the neurological and radiological abnormalities in our patients may have been due to neurotoxicity of vindesine. PMID- 2312857 TI - Postoperative contrast enhancement in brain tumors and intracerebral hematomas: CT study. AB - Postcontrast cerebral CT was performed sequentially on days 3, 7, and 14 after surgery in 34 patients [11 with gliomas; 6 with metastatic tumors, and 17 with intracerebral hematomas (ICH)]. The purpose of this study was to investigate the natural course and mechanisms of postoperative contrast enhancement (CE) of the brain around the removed lesions. Contrast enhancement was noted on days 3-14 in 10 patients in whom the gliomas were partially or subtotally removed. The intensity of CE appeared to increase with time. Among the six patients in whom the metastatic tumors were totally removed, four showed no CE until day 14 after surgery. Contrast enhancement appeared on day 3 in one and on day 14 in another. In 12 patients with ICH, which had been evacuated during the first 5 days after hemorrhage, CE was not noted on day 3 but began to appear on day 7, and intensified on day 14 after surgery. Contrast enhancement was demonstrated on day 3 in four of the five patients in whom the ICH was removed later than 10 days after the hemorrhage. No CE was observed on days 3 through 14 in the one patient in whom the hematoma capsule was totally removed. The present study suggests that CE noted on day 3 after removal of gliomas and metastatic tumors seems to be caused by extravasation of contrast medium within the residual tumor, which is devoid of blood-brain barrier. Contrast enhancement noted in ICH cases and intensifying CE noted in tumors 7 days after surgery seems likely to be caused by neovascularization in the postoperative brain. PMID- 2312858 TI - CT and MR imaging of fourth ventricular meningiomas. AB - True fourth ventricular meningiomas are rare. We report two cases, one with typical CT, angiographic, and magnetic resonance (MR) appearances and one with atypical features of central cyst formation on CT and MR. The utility of MR in demonstrating intraventricular location in three imaging planes is illustrated. Given the rarity of these tumors, atypical features may preclude accurate preoperative diagnosis, even with MR. PMID- 2312859 TI - CT and MR imaging of myxofibroma of the jaws. AB - Three cases of myxofibroma of the jaws are presented: two involving the mandible and one the maxilla. Computed tomography was found to be superior to plain radiographs in demonstrating the extent of the lesions. A mandibular case was imaged with both CT and magnetic resonance (MR). Computed tomography was found to be superior in demonstrating the involvement of the bone cortical plate. The information obtained with CT and MR may be useful for the surgical management of these aggressive lesions. PMID- 2312861 TI - Periventricular involvement in CNS lymphomatoid granulomatosis: MR demonstration. AB - We report a case of intracranial lymphomatoid granulomatosis shown by magnetic resonance (MR) as a focal periventricular lesion. The patient had an undulant clinical course manifested by multiple peripheral and cranial neuropathies. Both the clinical course and the MR findings were difficult to differentiate from an unusual presentation of multiple sclerosis. Autopsy correlation was obtained after the patient succumbed to cardiopulmonary arrest during status epilepticus. PMID- 2312860 TI - Head and neck reconstruction with pectoralis major myocutaneous flap: CT evaluation. AB - Sixty-one CT scans in 20 patients who had undergone head and neck reconstructive surgery using a pectoralis major myocutaneous (PM-MC) flap were retrospectively evaluated to assess the usefulness of Ct in the follow-up of these patients. The normal CT findings in patients with PM-MC flaps are described. Of 13 cases with tumor recurrence, CT examination correctly detected recurrent masses in all cases, including 3 in which there was no clinical sign of recurrence. Postoperative masses mimicking tumor recurrence included deformed breast tissue, hematomas, lymphoceles, and abscesses. Computed tomography was of great value in the detection of tumor recurrence, but careful interpretation is required because a postoperative complication or anatomic alteration may lead to the erroneous diagnosis of tumor recurrence. PMID- 2312862 TI - Extra-CNS metastases of glioblastoma: CT and MR studies. AB - The case of a 29-year-old man with glioblastoma and multiple metastases outside the CNS is presented. Cervical lymph node involvement was ascertained with CT and magnetic resonance (MR), and numerous bone metastases were detected with skeletal scintigraphy. The extent of the cervical tumor and its relationship to the carotid artery could be better assessed with MR than with CT. The patient died despite repeat operations, radiotherapy, and intraarterial systemic chemotherapy. The importance of radiological screening for detecting glioblastoma metastases in patients with long survival is discussed. PMID- 2312863 TI - PET evaluation of spinal cord tumor using 11C-methionine. AB - A cervical cord tumor was examined with positron emission tomography using L methyl-[11C]methionine. The radioactive tracer accumulated in the solid parts (but not in the associated cysts) of the neoplasm, which at histology was found to be an ependymoma. PMID- 2312865 TI - CT demonstration of intrapulmonary right brachiocephalic vein associated with an azygos lobe. AB - We describe a rare anomaly demonstrated by CT in which the right brachiocephalic vein follows an extramediastinal course in the anterior portion of the azygos fissure. PMID- 2312864 TI - CT demonstration of spinal epidural emphysema after strenuous exercise. AB - We report a case of spinal epidural emphysema after strenuous exercise. The emphysema was without clinical signs and disappeared after 2 weeks. PMID- 2312866 TI - Fat-fluid level in pleural effusion as a complication of a mediastinal dermoid: CT characteristics. AB - The CT findings in a 24-year-old woman with acute chest symptoms revealed excess mediastinal soft tissue and a fat-containing cavity. A fat-fluid level in a pleural effusion suggested preoperatively the diagnosis of mediastinal teratoma, which had leaked into the pleural space. PMID- 2312867 TI - Struma ovarii: CT and MR findings. AB - A case of pure struma ovarii is reported with its CT, magnetic resonance (MR), and pathologic findings. Both MR and CT revealed a complex mass composed of solid elements and multiple cysts; CT revealed calcifications not apparent on MR. PMID- 2312868 TI - CT diagnosis of traumatic abdominal aortic rupture. AB - Blunt injury to the abdominal aorta has been previously reported. Due to the severity of the lesion, radiologic studies other than aortography are rarely undertaken prior to emergency surgery. We report a case in which CT initially demonstrated an angiographically and surgically proven rupture of the infrarenal abdominal aorta due to blunt trauma. PMID- 2312869 TI - MR imaging of transarticular skip metastases from distal femoral osteosarcoma. AB - We describe a case in which magnetic resonance (MR) imaging of a distal femoral osteosarcoma showed transarticular skip metastases in the proximal tibia. These lesions were not found by conventional radiography, bone scintigraphy, or CT. Since detection of transarticular skip metastases has an important influence on surgical management, MR imaging of metaphyseal osteosarcomas should always include the bone on the opposite side of the joint. PMID- 2312870 TI - MR imaging of early fibrodysplasia ossificans progressiva. AB - Fibrodysplasia ossificans progressiva is a rare disorder characterized by progressive heterotopic bone formation in connective tissue and muscle in association with congenital skeletal anomalies. The disease usually leads to extensive immobility and eventual disability. We report the magnetic resonance findings in a boy prior to ossification of his soft tissue masses. PMID- 2312871 TI - CT appearance of an oncocytic papillary cystadenoma of the larynx. AB - The CT appearance of an oncocytic papillary cystadenoma of the right laryngeal false cord is presented. This unusual tumor of the larynx with similar CT appearance to that of a cyst of the laryngeal saccule is discussed. PMID- 2312872 TI - CT demonstration of calcifying sludge balls. PMID- 2312873 TI - The onset of mammary secretion of medium-chain-length triglyceride fatty acids in the cow milked pre-partum. AB - Six Friesian cows were milked daily, and arterial and mammary venous blood samples were taken between day 266 of gestation and day 6 after parturition. Samples of blood plasma were analysed for their content of acetate and progesterone, and mammary secretion for potassium, isocitrate, 2-oxoglutarate and triglyceride fatty acids. The onset of secretion of medium-chain triglyceride fatty acids was preceded by, or coincided with, increases of potassium and isocitrate concentration in the secretion. The onset of fatty acid secretion was not accompanied by any change in the gland's extraction of acetate from the circulation, and did not occur at a consistent time relative to parturition or changes in plasma progesterone concentration. PMID- 2312874 TI - Compensatory milk production within the bovine udder: effects of short-term non milking of single quarters. AB - Daily quarter-milk yields of eight high-yielding cows (24-28 kg/d) and eight heifers (14-24 kg/d) were measured to examined to examined compensatory changes in milk production between quarters within an udder. Either one, two or three quarters per cow were left unmilked for 12 d, in early or late lactation, and then all quarters of all cows were milked normally for a further period of 12 d. Concentrate feeding levels were constant throughout the experiment. The mean daily yield per cow fell to 26, 59, and 75% during the period of milking either one, two or three quarters respectively. Twelve days after resumption of normal milking the total daily yield per cow was the same for cows continuously milked in two, three or all four quarters. Daily yield in cows with only one quarter milked continuously recovered to only 78% of the level of the pretreatment period. During the treatment period, the mean daily yield of the continuously milked quarters increased by almost 14% for cows milked in one quarter only, by more than 10% for two quarters milked, and by 4% per quarter if three quarters were milked. Milk yields of these quarters remained above their pretreatment levels when milking was resumed in the adjacent quarters. There was no difference in the compensatory effect between cows and heifers in early lactation, but the compensatory effects were lower in the lower in late lactation heifers. PMID- 2312875 TI - Effect of cleaning-in-place disinfectants on wild bacterial strains isolated from a milking line. AB - Two cleaning-in-place disinfectant systems (alkaline-acid, alkaline-Cl2) were tested on wild bacteria isolated from a milking line. Most of the isolated strains were Gram-negative and capsule-positive. The effect of milk and cream on the resistance of the wild strains to the cleaning systems was tested. Suspension tests did not show the resistance of bacteria whereas the surface test showed high resistance towards all cleaning-agents. Milk had a protective effect only on the surfaces whereas cream showed mild protection in suspension and complete protection on the surfaces. It was concluded that the growth pattern of contaminants on surfaces needs further attention and the laboratory suspension tests do not correlate with the practical situation. Disinfectant tests based on bacterial growth on the surface are of importance. PMID- 2312876 TI - Milk protein polymorphism in Danish dairy cattle and the influence of genetic variants on milk yield. AB - In milk samples from 549 cows of the breeds Danish Jersey, Red Danish Dairy Cattle (RDM), and Black and White Danish Dairy Cattle (SDM) the genetic polymorphisms of the alpha-s1, beta and k-casein and beta=lactoglobulin (beta-Lg) loci were determined by isoelectric focusing in agarose gels. The results of the screening were compared with results obtained by Larsen and Thymann. In addition, the genetic linkage of the three casein loci was studied , and the association between milk protein genotypes and yields in first and second lactations of milk, fat and protein were investigated. The distribution of genotypes of all four milk protein systems was different from breed to breed. For Jersey cows, significant differences in the gene frequencies from the results of the 1966 investigation were found for alpha-s1 and k-casein and beta-Lg. For SDM cows a change in the k casein frequency had occurred whereas for RDM cows no changes were found. Linkage between some of the casein loci was found within all three breeds. For the RDM breed the possible linkage between alpha-s1-casein and the other caseins could not be tested because nearly all the cows were homozygous for the alpha-s1-casein B genotypes. beta-Casein genotypes were associated with yield parameters in all breeds. The A2A2 genotype of this protein gave higher yields of milk, fat, and protein in the second lactation than the A1A1 genotype. PMID- 2312877 TI - Ability of bovine mammary macrophages to enhance proliferation of autologous blood and mammary secretion lymphocytes. AB - Cells were obtained by centrifuging the mammary secretion of healthy udders of 19 cows during the dry-period and during mid-lactation. The suspended cells were incubated in plastic wells. Those adhered cells classified as mammary macrophages were incubated with pokeweed mitogen (PWM). Autologous peripheral blood lymphocytes were added to wells containing untreated macrophage cultures or cultures pretreated with PWM. In seven cows autologous dry-period mammary lymphocytes were added instead of blood lymphocytes. The macrophages + lymphocyte cultures were subjected to the lymphocyte stimulation test (LST). For comparison, peripheral blood lymphocytes and dry-period secretion lymphocytes were also subjected to the LST in the presence of PWM. In all cases, mitogenic responses were higher in pretreated macrophage cultures than in background control cultures. The stimulation indices (SI) showed that PWM-pretreated dry-period mammary macrophages enhanced the proliferation of autologous peripheral blood lymphocytes to a greater extent than did blood lymphocytes plus PWM (49 +/- 10 v. 30 +/- 6; P less than or equal to 0.05). Mammary macrophages taken from the same cows but during midlactation also clearly induced proliferation of autologous peripheral blood lymphocytes but to a lesser extent than dry-period macrophages (16 +/- 2 v. 49 +/- 10; 16 +/- 2 v. 30 +/- 6; P less than or equal to 0.01 and P less than or equal to 0.05). The PWM pretreatment of mammary macrophages increased the proliferation of autologous dry-period mammary lymphocytes by at least a factor of three (28 +/- 8 v. 8 +/- 2 P less than or equal to 0.05). The present results indicate that bovine mammary macrophages pretreated with PWM enhance proliferation as well as modulation of mammary and peripheral blood lymphocytes. The modulation of lymphocyte stimulation as demonstrated here in vitro, has great significance regarding aspects of local immunostimulation related to modern treatment of mastitis. PMID- 2312878 TI - Treatment of Staphylococcus aureus mastitis with penicillin and novobiocin: antibiotic concentrations and bacteriologic status in milk and mammary tissue. AB - Cows with Staphylococcus aureus mastitis received either one or two intramammary infusions containing 100,000 U penicillin G and 150 mg novobiocin. Milk and tissue samples were obtained from each quarter. Peak mean penicillin and novobiocin concentrations from antibiotic-positive tissue samples were .013 U/mg and .06 microgram/mg, respectively, for quarters treated once. Quarters treated twice had peak mean penicillin and novobiocin concentrations of .057 U/mg and .06 microgram/mg, respectively. Viable Staphylococcus aureus were isolated intermittently from milk and tissue samples of quarters positive for penicillin and novobiocin for both treatment groups. Histological analysis of mammary parenchyma demonstrated marked decreases in luminal area and increases in connective tissue area and leukocyte infiltration in S. aureus-infected quarters compared with uninfected controls, suggesting that reduction in milk collecting space and presence of inflammatory changes may be responsible for poor drug distribution. PMID- 2312879 TI - Effect of poultry waste feeding on intake, body weight and milk yield of Holstein cows. AB - Forty lactating Holstein cows were fed 0, 5.9, 11.7, or 17.4% processed poultry excreta in total mixed rations. The effect of treatment was evaluated on feed intake, BW, milk yield, and composition. Processes poultry excreta appeared to be well accepted by cows even when included in rations at 17.4% of total DM. Mean DM intake averaged 19.3, 19.7, 19.5, and 19.7 kg/d for cows fed 0, 5.9, 11.7, and 17.4% processed poultry excreta, respectively. Body weight change averaged 2.0, 1.7, -1.7, and 1.4 kg/wk from 90 to 180 d of lactation for cows fed from 0 to 17.4% processed poultry excreta, respectively. Fat-corrected milk (4%) yield was similar among treatment groups, averaging 24.2, 26.1, 24.6, and 25.1 kg/d for cows fed 0, 5.9, 11.7, and 17.4% processed poultry excreta. No differences were found for milk and fat yields of percentage fat among treatment means. No off flavors in milk could be attributed to processed poultry excreta added to feed. Processed poultry excreta fed up to 17.4% of total mixed rations supported both adequate feed intake and high milk yields of mid-lactation cows. PMID- 2312880 TI - Influence of synchronizing protein and starch degradation in the rumen on nutrient utilization and microbial protein synthesis. AB - A 4 x 4 Latin square design with four multiparous cows in midlactation fitted with duodenal cannulae was used to determine the effect of synchronization of protein and starch degradation in the rumen on nutrient availability in lactating cows. As major starch and protein sources, diets contained: barley plus cottonseed meal; barley plus brewers dried grains; milo plus cottonseed meal; and milo plus brewers dried grains. Experimental periods were 12 d and consisted of 8 d adjustment and 4 d collection. Chromium oxide was used as the marker to determine digestibility and nutrient flow from the rumen. Microbial protein synthesis was estimated from nucleic acid content in duodenal samples. Apparent and corrected rumen digestibilities of DM, organic matter, CP, and starch were higher for diets containing barley than milo but were not affected by protein source. For diets containing barley and milo, starch digested postruminally averaged 820 and 2190 g/d and percentage digestibility was 70 and 77%. No difference among diets was found in DM, organic matter, and CP flow to the small intestine; however, microbial N synthesis was higher in diets containing barley than in diets containing milo. PMID- 2312881 TI - Effect of lasalocid on performance of lactating dairy cows. AB - Thirty-two midlactation dairy cows were fed either a typical dairy diet or the same diet plus 340 mg lasalocid/d for 98 d. Diets were 65% forage (alfalfa and corn silage) and 35% concentrate (DM basis). Lasalocid did not affect production of milk (21 kg/d) or FCM (20 kg/d) or milk composition. Dry matter intake was slightly lower for cows consuming lasalocid than for control cows (19.6 vs. 20.6 kg/d). Lasalocid improved energetic efficiency by about 20% during the first 2 wk of the experiment, but treatment effects diminished as the experiment progressed. The period in which lasalocid had significant effects on energetic efficiency was also the period in which lasalocid increased ruminal propionate and decreased ruminal acetate concentrations. On d 7 of the experiment, cows fed lasalocid had lower acetate to propionate ratios as compared with control (3.0:1 vs. 3.7:1). No effect of treatment was observed on ruminal VFA during the remainder of the experiment. These data are interpreted to show that lasalocid improved the efficiency of converting dietary digestible energy into NE1 by altering ruminal fermentation, but this effect was relatively short-lived, since treatment effects on ruminal VFA patterns and energetic efficiency became negligible by 28 d. PMID- 2312882 TI - Treatment of dairy cows with recombinant bovine somatotropin: genetic and phenotypic aspects. AB - Thirty-four multiparous and primiparous Holstein cows were utilized to examine the association between the response to long-term administration of recombinant bovine somatotropin and the cow's phenotypic and genetic production potential. Cows representing a range of phenotypic and genetic production potentials were assigned to one of four treatment groups: 0, 12.5, 25.0, or 50.0 mg recombinant bovine somatotropin daily. They were injected daily for 266 d beginning on d 24 to 35 postpartum. Pretreatment milk and fat yields were used to predict daily yields over the lactation and allowed treatment groups to serve as their own controls. Actual minus predicted yield estimated the response to treatment for milk, fat, and FCM for each cow. Milk composition (fat, protein, and lactose percentage) was not significantly affected by treatment. Response in yield for milk, fat, and FCM was significant during the treatment period (266 d). Milk yield increased by 18.5, 19.9, and 21.4%; fat yield increased by 13.4, 20.3, and 18.1%; and FCM increased by 16.3%, 19.7%, and 21.1% after receipt of 12.5, 25.0 and 50.0 mg recombinant bovine somatotropin, respectively. Differences in response were not significant. The dramatic effect recombinant bovine somatotropin has on production requires that alternative approaches be adopted in the future for accurate genetic evaluation of sires and dams if somatotropin is discriminantly used in the national herd. PMID- 2312883 TI - Prediction of transmitting abilities for Holstein type traits. AB - Heritabilities and genetic and phenotypic correlations among 14 linear type traits were estimated from Holstein Association data by multiple trait REML. Data used for parameter estimation were records of 779,391 daughters of 871 sires included in the January 1988 sire evaluation. Each daughter was represented by her appraisal closest to 30 mo of age. Highest heritability was .37 for stature, and lowest was .10 for foot angle. Gains in reliability from using correlated traits in multiple trait prediction were large for some traits (up to 60% for foot angle for cows). Final score variance parameters were estimated from 953,596 records, which were 43% of records included in the national sire evaluation. Sire models that adjusted or did not adjust for merit of mates were compared. Heritability of final score was .27 with adjustment for merit of mates by subtraction of predicted transmitting ability of dam from daughter's record compared with .29 if mate was ignored. Evaluations for type for several popular older sires were reduced moderately by adjustment for merit of mates, but estimated genetic trend increased slightly. An improved genetic grouping procedure that considers group effects as inherited was adapted for use in sire models. Parameter estimates and models presented were implemented by the Holstein Association for computing July 1988 genetic evaluations for linear traits and final score. PMID- 2312884 TI - Estimation of repeatability of calving ease in Canadian Holsteins. AB - Restricted maximum likelihood was used to estimate repeatabilities and heritabilities for calving ease from a data set of 636,972 Holstein parturitions obtained from the Quebec Dairy Herd Analysis Service. Subsets of the data, chosen to reflect different stages of cow maturity, were analyzed separately and compared. Initial least squares analyses were used to define the fixed effects to include in the model. The effects of herd-year-season, sex of calf, parity, and sex by parity interaction were significant in all subsets. Age and parity by age interaction were significant in subsets with primarily younger animals. Variances for sire of calf, cow, and residual effects were then estimated by REML. Repeatabilities ranged from 5.98 to 7.87% and heritabilities for calving ease as a direct effect ranged from 1.97 to 4.70%. PMID- 2312885 TI - Conception rate, growth, and lactation of dairy heifers treated with recombinant somatotropin. AB - Eighty Holstein heifers (295 kg; 13 to 16 mo of age) were allotted to two treatments in a completely random design experiment to determine the effect of daily injections of recombinant bovine somatotropin on conception, growth, and subsequent lactation. Heifers were treated with either 41.2 mg of bovine somatotropin or saline daily for 5 mo. Breeding was initiated 2 mo after the start of bovine somatotropin or saline treatment. Conception rates and number of services per conception did not differ between treatments. During the injection period, heifers treated with bovine somatotropin gained .18 kg/d faster than control heifers. During the 5 mo following the treatment period, control heifers gained .12 kg/d faster than the heifers that had received bovine somatotropin so that at the end of this 10-mo period weights of heifers in the 2 groups were similar. The heifers treated with bovine somatotropin had a greater increase in both hip height and pelvic size compared with control heifers during the 5-mo treatment period. Calving difficulty scores were similar between treatments. Treatment with bovine somatotropin prior to and during breeding of these heifers did not affect milk yield after first calving compared with control heifers. PMID- 2312886 TI - The effect of whole ejaculate filtration on the morphology and the fertility of bovine semen. AB - A Sephadex G-15 filtration method was developed to remove abnormal and nonmotile bull sperm from an entire ejaculate. The efficiency of filtration was determined by adding freeze-killed sperm to the ejaculate or using ejaculates with elevated numbers of abnormal cells induced by scrotal insulation. A fertility trial, using split ejaculates, compared fertility of filtered and unfiltered semen. After filtration, samples with 0, 25, and 50% killed cells added contained 77 to 81% motile cells. Addition of 75% killed sperm resulted in significant decrease (52%) of motile cells following filtration. Morphologic examination of semen with elevated numbers of abnormal cells revealed higher percentages of sperm with normal shaped heads and normal or swollen acrosomes after filtration than in unfiltered samples. Percentage of pear-shaped heads, lifted acrosomes, and bent tails decreased after filtration. Six high fertility and six low fertility bulls were used to evaluate fertility of filtered semen. Filtering increased motile sperm from 51 to 57% and from 36 to 50% for the high and low fertility bulls, respectively. The 60- to 90-d nonreturn rates for high fertility bulls were not increased by filtering (73 vs. 72%). However, filtering significantly improved the nonreturn rates for the low fertility bulls (61 vs. 67%). PMID- 2312887 TI - Dentinal temperature transients caused by exposure to CO2 laser irradiation and possible pulpal damage. AB - An investigation is described that attempts to establish, in vitro, the characteristics of heat transference following laser irradiation of bovine dentinal tissue and the relationship with the periodicity of radiation. The results of this study appear to indicate that at depths of overlying dentine of up to 3 mm, laser-induced thermal injury to the pulp is a definite possibility. Fail-safe facilities to prevent build up of heat must be incorporated into the design of dental lasers to allow their beneficial effects to be utilized without the risk of iatrogenic damage. PMID- 2312888 TI - Factors influencing the caries experience of a group of children at the ages of 11-12 and 15-16 years: results from an ongoing epidemiological survey. AB - An analysis of factors influencing the caries experience of adolescents in South Wales is presented. Approximately 1000 children were assessed for caries status and oral cleanliness in 1980 when aged 11-12 years and again in 1984 when aged 15 16 years. In addition, on both occasions, the children completed detailed questionnaires on dental health-related topics. When aged 11-12 years, the observed mean DMFT, DMFS and DFS scores of the children were 4.0, 6.7 and 5.5 respectively. The corresponding scores at age 15-16 years were 6.5, 11.8 and 10.2. A preliminary analysis using conventional multiple regression techniques revealed that a number of factors had a significant influence on the caries experience of the children. The significance of the factors depended on the sex of the population subgroup, the age of the children and the particular caries index studied. However, at both ages the factors of most significance were the number of erupted teeth, total mean plaque score and the reported amount of money spent on sweets per week. A further evaluation using analysis of covariance with the number of erupted teeth and surfaces as the covariates confirmed the significant influence of the total mean plaque score and amount of money spent on sweets. In addition, both analyses indicated that toothbrushing frequency and social class had a significant influence on the caries experience of boys. PMID- 2312889 TI - Clinical behaviour of high-copper amalgams with time, site, size and class of cavity preparation. AB - In this study 767 amalgam restorations placed in the posterior permanent teeth of 122 patients were evaluated at 6-monthly intervals up to 2 years. Six commercially available high-copper alloy amalgams were assessed for surface roughness, surface tarnish, marginal staining and marginal fracture and the results were related to product, restoration age, restoration cavity class type, restoration size (normal or large Class II preparations) and tooth type (premolar or permanent molar). Dispersalloy (Johnson and Johnson, East Windsor, USA) gave restorations which were overall superior for the clinical characteristics examined. Large restorations on the occlusal surfaces of molar teeth showed more signs of deterioration over the study than did other restoration types. However, all restorations remained clinically satisfactory throughout the study. PMID- 2312890 TI - Rapid monitoring of fluoride (F-) levels in blood plasma. AB - Evidence exists that plasma F- concentrations of 1.0 part/10(6) are nephrotoxic and that much lower levels disturb enamel mineralization. Ingested F(-) containing gels, tablets and toothpastes all raise plasma F- levels significantly, as does prolonged exposure to fluorine-containing anaesthetic gases. There is, therefore, a continuing need to determine the total F- burden accruing in any given individual from multiple sources, as well as the average plasma F- burden which could be carried without risk to kidneys or teeth. To meet this need by facilitating fast and accurate monitoring of plasma F- levels, a new method has been devised and tested. A specific ion F- electrode in conjunction with a combination pH electrode forms a differential cell very sensitive to low concentrations of F-. When compared with the performance of a single F- electrode plus Ag/AgCl reference electrode, the differential cell is not only as consistent and accurate but also has a much shorter response time (2 vs. 20 min) and requires a much smaller sample volume (0.05 vs. 1.0 ml). In healthy subjects the mean plasma F- level was 0.044 (+/- 0.001) parts/10(6); in three patients undergoing prolonged (24 h) sedation with the fluorine-containing gas isoflurane, mean plasma F- rose to 0.275 (+/- 0.025) parts/10(6). No binding of F- to plasma components occurred at the operating pH (1.2) of the differential cell and plasma could be stored for at least 40 days at low temperature (4 degrees C) without alteration to measured F- values. PMID- 2312891 TI - Fluoride analysis in nanoliter- and microliter-size fluid samples. AB - A variety of techniques is described for measuring fluoride in volumes of from 0.005 to 5 microL, including: (1) micropipette procedures for transference and dilution of samples, (2) construction of miniature and micro fluoride-selective electrodes, and (3) methods for adapting standard electrodes for micro- and semi micro volumes. These described techniques have a number of advantages, including speed of analysis, high accuracy, and adaptability to many types of fluid samples. Recent studies involving use of these procedures include the analysis of fluoride in: (1) plaque fluid samples from single sites before and after topical fluoride administration, (2) tooth mineral samples recovered by acid-etch or microdrill biopsy of enamel, and (3) fluid recovered from the interior of the tooth during simulation of the caries process. PMID- 2312892 TI - Dependence of in vitro demineralization of apatite and remineralization of dental enamel on fluoride concentration. AB - The anti-caries activity of fluoride is contributed to in several ways. Two major aspects of fluoride action are (i) the inhibition of demineralization at the crystal surfaces within the tooth, and (ii) the enhancement of subsurface remineralization resulting in arrestment or reversal of caries lesions. Fluoride present in the aqueous phase at the apatite crystal surface may play a determining role in the inhibition of enamel or dentin demineralization. In one part of the present study, the initial dissolution rate of synthetic carbonated apatite in acetate buffers was measured with fluoride present in the buffer in the 0-2.6 mmol/L (0-50 ppm) range. Inhibition of demineralization was shown to be a logarithmic function of the fluoride concentration in solution. In the second part of the present study, an in vitro pH-cycling model was used for determination of the effect on net de/remineralization of enamel by treatment solutions containing fluoride in the 0-26 mmol/L (0-500 ppm) range. The net mineral loss was shown to be negatively related to the logarithm of the fluoride concentration. These studies have demonstrated an exponential quantitative relationship between fluoride concentration and inhibition of apatite demineralization or enhancement of remineralization. The clinical implications are (i) that simply increasing fluoride concentration may not necessarily give increased cariostatic benefit, and (ii) that improving the means of delivery of relatively low fluoride concentrations for longer times should be more appropriate for enhancing clinical efficacy. PMID- 2312893 TI - Recent trends in dental caries in U.S. children and the effect of water fluoridation. AB - The decline in dental caries in U.S. schoolchildren, first observed nationwide in 1979-1980, was confirmed further by a second national epidemiological survey completed in 1987. Mean DMFS scores in persons aged 5-17 years had decreased about 36% during the interval, and, in 1987, approximately 50% of children were caries-free in the permanent dentition. Children who had always been exposed to community water fluoridation had mean DMFS scores about 18% lower than those who had never lived in fluoridated communities. When some of the "background" effect of topical fluoride was controlled, this difference increased to 25%. The results suggest that water fluoridation has played a dominant role in the decline in caries and must continue to be a major prevention methodology. PMID- 2312894 TI - Dental caries prevalence and the use of fluorides in different European countries. AB - Data in a WHO report relating caries prevalence and the use of fluorides in different European countries were compared with data obtained directly from investigators in the field of oral epidemiology. The reliability of DMFT indices of 12-year-old children, mentioned in the WHO report, appeared sufficient to make comparisons between countries on the basis of these data. The WHO data files on the different applications of fluoride were incomplete. When figures were present, they were not always in agreement with those from the investigators. A decrease of the DMFT indices could be shown in a large number of countries. In further comparative studies between European countries, cultural differences (in dietary habits, for instance) should be taken into account. PMID- 2312895 TI - The importance of accurate reporting on liposuction surgery to the public. PMID- 2312896 TI - Rees Lighted Freedom Retractor for scalp reduction. PMID- 2312897 TI - Facilitating surgical ablation of lesions in the conchal cavum and around the external auditory meatus, with subsequent 2-stage flap reconstruction. AB - Coverage of surgical defects of the external auditory meatus and surrounding areas can be singularly challenging. Partial detachment of the lower pinna may facilitate surgical exposure and the movement of tissue from periauricular locations. A high level of esthetic reconstruction can be accomplished. PMID- 2312898 TI - Treatment of striae distensae with topical tretinoin. AB - The experience of 20 patients with striae distensae of varying etiologies and the treatment with topical tretinoin is described. Of the 16 patients who completed the study, 15 had significant improvement in their clinical picture. PMID- 2312899 TI - Immunosuppression in patients with metastatic squamous cell carcinoma from the skin. AB - Sixteen of 70 patients with metastatic squamous cell carcinoma (SCC) from the skin had evidence of clinical immunosuppression. In addition to patients with lymphoproliferative disorders or renal failure, those with cicatricial pemphigoid and those undergoing chronic oral corticosteroid therapy were identified as being at high risk. Host immune surveillance appears to play a major role in determining the metastatic potential of cutaneous SCC. PMID- 2312900 TI - The use of VP16 and cisplatin in the treatment of Merkel cell carcinoma. AB - A 70-year-old male with regionally recurrent Merkel cell cancer obtained a complete remission with three cycles of VP16 and cisplatin. His response was consolidated with local radiation therapy. Two additional patients have been reported to have responded to the same combination. Chemotherapy consisting of either cyclophosphamide, vincristine, and doxorubicin or VP16 and cisplatin should be considered in locally recurrent Merkel cell cancer. PMID- 2312901 TI - Hair transplants in Barcelona. PMID- 2312902 TI - Acne keloidalis. PMID- 2312903 TI - Lactate measurement: plasma or blood? PMID- 2312904 TI - Mechanics of the circulation during cardiopulmonary resuscitation. Pathophysiology and techniques (Part I). PMID- 2312905 TI - Mechanics of the circulation during cardiopulmonary resuscitation. Pathophysiology and techniques (Part II). PMID- 2312906 TI - Changes in plasma and whole blood lactate in response to arterial occlusion. AB - The development of lactic acidaemia in the adult forearm in response to partial and total arterial occlusion is described in both plasma and whole blood. Under conditions of total occlusion of the brachial artery lactate levels in the plasma compartment rise at a significantly faster rate; mean difference in gradients 11.6 95% confidence limits -15.6 and -7.6. Thus in these conditions they provide a more sensitive index of tissue hypoxia. Under conditions of partial occlusion there is no significant difference; mean difference in gradients 1.0 95% confidence limits 9.4 and -7.3. Though plasma lactate levels are more sensitive to the ischaemic state in certain circumstances, whole blood measurements are equally applicable to the monitoring of trends in blood lactic acid. PMID- 2312908 TI - The cerebral function analysing monitor in paediatric medical intensive care: applications and limitations. AB - Practical guidelines for continuous single channel EEG monitoring using the Cerebral Function Analysing Monitor (CFAM) have been outlined based on experience of 54 critically ill comatose and/or paralysed sedated children monitored for up to 9 days during the acute phase of illness. Fall in amplitude and slowing of frequency following either a cerebral insult or barbiturate administration as well as paroxysmal events were readily recognisable in the CFAM traces. Such changes could be used to (1) identify effects of cerebral insults (acute or cumulative), (2) recognise unstable patients exquisitely sensitive to aspects of standard care and (3) evaluate seizure control. Despite these useful contributions to clinical care, significant limitations were apparent. It is recommended that CFAM monitoring should be combined with serial conventional EEG recording in order to check the appropriateness of the cortical areas being monitored, the quality and type of signal being processed as well as the significance of the 1 or 2 channel CFAM findings in relation to global cerebral function. PMID- 2312907 TI - Incidence of forearm and hand ischaemia related to radial artery cannulation in newborn infants. AB - We report the incidence of transient and permanent ischaemia of the forearm and hand caused by radial artery cannulation in a series of 98 newborn infants. Birth weight ranged from 550 to 3920 g (median 1600 g) and gestational age ranged from 26 to 40 weeks (median 31 weeks). In 4 of the 98 infants transient ischaemia of the forearm and/or hand occurred. In three infants the onset of ischaemia was probably related to thrombo-embolic events and in one infant to inadequate palmar collateral circulation. Permanent ischaemic damage with tissue loss did not occur in any infant. It is concluded that permanent ischaemic damage to the forearm and/or the hand with tissue loss, attributable to radial artery cannulation, is seldom encountered in newborn infants. In minimizing the risk of ischaemia, careful assessment of palmar collateral circulation prior to cannulation and of all factors predisposing to the onset of ischaemia is essential. Immediate removal of the catheter at the earliest signs of ischaemia, is essential to prevent ensuing tissue loss. PMID- 2312909 TI - Accidental hypothermia with cardiac arrest: complete recovery after prolonged resuscitation and rewarming by extracorporeal circulation. AB - A 51-year-old male remained immersed in sea water (6 degrees C) for 40 min. Brought ashore, the ECG showed asystole. Advanced life support was immediately commenced. On arrival in hospital his rectal temperature was 27 degrees C, but continued to fall to 24 degrees C. The ECG remained isoelectric. Cardiopulmonary resuscitation was continued until extracorporeal circulation was established 190 min after rescue. Upon rewarming ventricular fibrillation occurred which was converted to sinus rhythm with a bolus of lignocaine followed by D.C. conversion at 31.5 degrees C. When rewarming was complete after 60 min, signs of severe heart failure became evident. Sternotomy and pericardiotomy were performed to exclude cardiac tamponade. After 60 min of re-perfusion the patient was be weaned from bypass supported by a high-dose vasopressor infusion and nitroglycerine. He was discharged after 13 days with no evidence of any permanent organ damage. Given the advantage of providing circulatory support, extracorporeal circulation may be useful when rewarming hypothermic victims with cardiac arrest. PMID- 2312910 TI - A case of the peanut syndrome in an adult. PMID- 2312911 TI - Maintaining the ethic of caring in nursing. PMID- 2312912 TI - Epidemiological and statistical aspects of the AIDS epidemic. PMID- 2312913 TI - A critical review of the use of Rogers' model within a special hospital: a single case study. AB - This case study presents a problematic patient who has been resident in a special hospital for mentally handicapped people for years due to a gross sexual fantasy disorder, continuous self-injurious behaviour and an array of disordered conducts which resulted in negative nursing reports. The introduction of Rogers' model, with its abstract finer conceptualizations produced an alternative framework by which to assess the patient. This holistic interactive model generated a paradigmatic shift in the nursing perceptions, at a conceptual level, which was manifested in their reporting behaviours. The results appeared to indicate a sudden and dramatic change in the patient's behaviour. However, alternative interpretations proved the more convincing on closer analysis. The use of Rogers' framework proved difficult in its practical application due to its underpinning requirements for role adoption and negotiation, both being problematic in a secure environment. PMID- 2312914 TI - Implementing the Roy model: challenges for nurse educators. AB - The experience of selecting and implementing a nursing model appropriate to the nursing course in the first year of the generic baccalaureate programme of the University of Ottawa School of Nursing is described. Many challenges surfaced for the professors in year one as this curriculum change was implemented. Four challenges: (1) adapting the course to be congruent with the Roy model, (2) developing teaching tools suitable for student learning, (3) sequencing of content for student learning, and (4) obtaining competent role models, and how they were met, are discussed. PMID- 2312915 TI - Trends in nursing of families. AB - The authors describe their observations of three trends in the nursing of families: namely, increased diversity in nursing practice; increased research; and increased family content in academic settings. These trends have major implications for nursing practice, research and education. The authors speculate on the implications and their effect on the families for whom nurses care. PMID- 2312916 TI - A description of clients nursed by community psychiatric nurses whilst attending English National Board Clinical Course No. 811: clarification of current role? AB - The English National Board Clinical Course No. 811 is a 36-week preparation for community psychiatric nurses (CPNs). Unlike health visiting or district nursing the course is not yet a mandatory prerequisite for practice and it has been estimated that, nationally, 23% of all CPNs have been awarded the certificate to date. There are currently 24 course centres in England, offering 420 places annually. The completion of a care study by the course student is a curriculum requirement. The present study aimed to establish the characteristics of clients chosen by course students for such work whilst attending the course in an attempt to obtain a 'proxy' measure of the current CPN role nationally. A stratified random sample of eight course centres was selected--four based in schools of nursing, and a further four located in establishments of higher education. Then within each course centre a stratified random sample of students was selected, who each completed a postal questionnaire. A 79% response was obtained. The results are described and discussed within the context of the CPN's developing role. The findings suggest that many CPNs conceptualize their role and function, to use Caplan's terminology, at the primary prevention level, and see their work as being located firmly in primary health care settings. The desirability of this orientation to CPN intervention is examined, acknowledging both mental health service developments and the wider educational implications. PMID- 2312917 TI - Motivation and drug dependency: a preliminary evaluation of an assessment tool. AB - This paper describes a pilot project examining whether two research-based assessment instruments following a conflict model of dependency are of any clinical use. It is argued that the information they provide about client motivation towards treatment and about supporting and hindering influences during withdrawal is important for clinicians of any profession involved in a service to drug users. PMID- 2312918 TI - Role-playing as a method in nursing research. AB - This report describes a way in which role-playing can be applied in nursing research. The questions investigated were how much the memory capacity is influenced by different methods of providing information, and in what manner objective and comprehensive information about a disease with all its possible consequences is experienced by the recipient. To elucidate these questions, 48 healthy persons imagined that they had a chronic disease. The study was arranged as a 2 x 2 factorial design, the factors being group information versus individual information about the disease, and provision of the whole information at once versus division of the information into three parts separated by 15 minutes. The information was given orally and a structured interview was consequently conducted. After 1 week the subjects were telephoned and were asked to tell the investigator what they remembered about the disease. The results showed that the amount and type of information recalled was not affected by the way in which it was given. The information in itself, however, had the effect of making the subjects calmer. Several parallels between the results of the role playing study and observations in patients demonstrate that role-playing provides useful knowledge and should be applied to a greater extent in nursing research. PMID- 2312919 TI - Ethical dilemmas associated with small samples. AB - This paper describes the ethical dilemmas which the authors encountered when conducting qualitative research with samples consisting of a small number of participants. Ethical conflicts are explored in terms of the principles of autonomy, non-maleficience, and beneficience with examples from the authors' research experiences. Although there are no definitive resolutions to these conflicts, the paper may increase awareness of the special concerns which require further study and debate. PMID- 2312920 TI - Self-reflection in nursing teacher education. AB - The reality of health care is continuously changing. Therefore, nursing teachers have to encourage and promote a critical, inquiry-oriented approach to work. This demands self-reflection during the teacher education. Teaching training crystallizes the objectives of teacher education; the process of self-reflection should be seen especially there. PMID- 2312921 TI - Professional nurses' attitudes towards humour. AB - A study of the attitudes of 204 registered professional nurses' towards humour showed differences in the attitudes in two settings. Fishbein & Ajzen's theoretical framework of attitude development and measurement was used to guide the study. The positive functions of humour indicate that it is a useful strategy for nurses to employ in their professional work setting. Although the nurses held positive attitudes towards humour in both the professional and personal settings, they were less positive in the professional work setting. The findings indicate that a potentially useful nursing strategy is not being fully utilized by nurses. PMID- 2312922 TI - Persistence in breastfeeding: a phenomenological investigation. AB - The experience of mothers who continue to breastfeed when other alternatives are available has received little attention. To examine the underlying meaning of the reality of persisting with breastfeeding, a phenomenological approach is used. Based on interviews with breastfeeding mothers, the author explores the meaning of continuing to breastfeed in relation to a mother's decision to breastfeed, the problems encountered, the relationship between mother and baby, being committed and choosing a time to stop. The aim of the author is to stimulate thinking beyond taken for granted attitudes towards breastfeeding and to enhance understanding of what breastfeeding and continuing to breastfeed is like for mothers in a deeper more meaningful way. PMID- 2312923 TI - Moral education for nursing decisions. AB - This paper attacks the Kantian conception of mortality that predominates in our society and the rationalist educational strategies that flow from it. In its place it offers an Aristotelian conception of ethics in which sensitivity and feeling are important components of practical reason. It argues that a nurse's ethical concerns extend further than the several moral dilemmas discussed in the daily press and that those concerns should be responded to in moral education by a process called 'empowerment'. Empowerment seeks to develop confidence and sensitivity in the making of difficult decisions and does so by training habits, developing attitudes, and encouraging reflection on actions performed. PMID- 2312924 TI - Health visiting: a withering profession? AB - Over the past 2 years, community nursing appears to have been quietly marginalized within successive government health documents. The health visiting profession in particular looks to be under the greatest threat, and it is to that issue that the discussion will be addressed. The argument will be made that changing the content of health visiting practice in an attempt to solve the apparent problems, is not sufficient in itself to both protect and allow development of the profession for the 21st century. It is of more relevance to determine the direction for health visitors within the rapidly changing context of primary health care provision. The potentially worrying changes in the community health agenda for health visitors will be demonstrated by some analysis of the Cumberlege Report 1986, the 1987 White Paper Promoting Better Health, the Griffiths Report on Community Care 1988, and the NHS Review 1989 Working for Patients. Potential avenues for action are explored, including neighbourhood nursing, and a serious attempt at membership of primary health care teams within general practice. The conclusion is that health visitors need to indulge in some painful decision-making, in order to prevent the withering away of their profession within the newly emerging context for primary health care delivery. PMID- 2312925 TI - Power and collegial relations among nurses on wards adopting primary nursing and hierarchical ward management structures. AB - Power and collegial relations among nurses on a number of hospital wards were analysed using a mixed methodology. Half the wards had adopted primary nursing whilst the rest continued with hierarchical management structures. Nurses' interactions were recorded as they worked, as were those that occurred during the shift handover period. The nurses' own perceptions of their collegial relations were measured using a 'Likert scale' type of questionnaire. Qualitative analysis of the observational data suggested that genuine differences in the nature of the power relations existed between the laterally and hierarchically managed wards. Some of the nurses on the primary nursing wards were observed to identify and discuss solutions to their patients' nursing problems, whereas these were either not followed-up or referred to other health care workers on the traditionally managed wards. Statistical analysis of the questionnaires suggested that nurses on the primary nursing wards found their collegial communication to be significantly more collaborative than that of the nurses on the hierarchical wards. Comparison between specialties did not reveal a statistical difference. PMID- 2312926 TI - Treatment, torture, suffering, and compassion. PMID- 2312927 TI - AIDS and the duty to warn. PMID- 2312928 TI - Direct reimbursement of nurse practitioners in health insurance plans of research universities. AB - The purpose of this study was to explore the nature of health insurance coverage research universities offer their employees and the extent to which these employers offer options providing for reimbursement of services of independent nurse practitioners. A request for health insurance documents mailed to 77 public research universities resulted in a response rate of 83 per cent. A total of 75 per cent sent usable descriptions of insurance coverage for analysis. Among the respondents, 69 per cent (n = 40) reported offering insurance through Blue Cross/Blue Shield companies. Nursing services reimbursed generally included traditional nursing care such as private duty nursing and home health care. Coverage of nursing services that overlap with traditional medical practice, such as prenatal care and labor and delivery services of nurse midwives, anesthesia services of nurse anesthetists, psychiatric services of nurse specialists, and primary care nursing services of nurse practitioners, was less evident. Findings generally indicated that in spite of the presence of enabling or mandatory state legislation for third-party reimbursement of nursing services, legislation is not being implemented in many states by employers in their purchase of group policies. PMID- 2312929 TI - The nurse executive. The big picture. PMID- 2312930 TI - Faculty and student perceptions of effective clinical teachers: an extension study. AB - This extension study was conducted to (1) identify which characteristics of the effective clinical teacher are deemed most important by nursing students and faculty; (2) determine whether previous findings remain valid (are transferable); and (3) investigate whether the perception of effective teaching behavior shifts as students advance toward graduation. The research tool, a two-part questionnaire developed by Brown, was circulated among students and instructors at a university college of nursing in southwestern Ohio. The first section listed 20 characteristics of teachers to be rated, using a Likert-type scale, from "of most importance" to "of no importance." The second section required subjects to select and rank in order the five most important characteristics from the list of 20. Descriptive analysis was applied to the data, and findings were compared with those of Brown. The study suggests that both faculty and students favor articulate, knowledgeable clinical instructors who are "objective and fair" in student evaluation. There is a high degree of similarity between the responses of faculty and students, but differences emerge. Both value skills involving the student-faculty relationship over skills centering on the professional or personal attributes of the instructor. However, faculty respondents appear to place a higher value on instructor interest in patients, and students are more concerned with communication-related attributes. Faculty members place a greater value on showing interest in patients than do students. The results, when compared with Brown's findings, appear largely transferable, but significant differences appear. For example, faculty members ranked characteristics dealing with the clinical instructor's relationship with students to be more important than those dealing with professional competence--the opposite of Brown's results. This study shows the need for nursing institutions to implement programs to foster and to promote uniformly identified effective clinical teaching characteristics. Given the special challenges of clinical nursing education, graduate programs should also seek to teach the skills identified as most effective, and persons with the skills perceived as effective should be urged to enter clinical instruction and should be rewarded for success in this important area. PMID- 2312931 TI - The nurse in relationship.... PMID- 2312932 TI - The use of postural vital signs in the assessment of fluid volume status. AB - Postural or orthostatic vital signs, although frequently used in many clinical settings to aid in the diagnosis of fluid volume disturbance, can be a source of confusion. Practitioners often have questions about how to perform the test and may be uncertain about what results mean in various clinical situations. Some of this confusion is reflected in the literature, where studies on normal orthostatic responses seem to contradict clinically used parameters of "normal," and where very few studies appear on evaluating unusual responses as indicators of patients' fluid volume status. A review of existing literature is presented, in which relevant data are reviewed in terms of their impact on the use of this clinical sign. Recommendations regarding the use of the orthostatic test are given. PMID- 2312933 TI - Government intervention: is it necessary for nursing? PMID- 2312934 TI - Single-purpose institutions for nursing programs: to be or not to be. AB - This article examines the legitimacy of baccalaureate and higher degree nursing programs being offered by single-purpose institutions. The arguments in support of and in opposition to the concept are analyzed and discussed. The American Association of Colleges of Nursing position statement on single-purpose institutions is reviewed. The author concludes that there is no inherent flaw in the concept of single-purpose institutions as an appropriate vehicle for delivery of nursing education programs. She further concludes that those programs that have successfully completed the rigorous reviews associated with institutional and specialized accreditation have, in that process, earned the right to be recognized and respected as legitimate members of the higher education community. PMID- 2312935 TI - Scientific misconduct: myth or reality? PMID- 2312936 TI - Education. Redefining community. PMID- 2312937 TI - Topics of nursing research as presented at two international conferences. PMID- 2312938 TI - The annual physical comes of age. PMID- 2312939 TI - Suicide and the continuum of self-destructive behavior. AB - Suicide and self-destructive behavior are strongly influenced by a negative thought process, referred to here as the "voice." The voice process represents a well-integrated pattern of thoughts, attitudes, and beliefs, antithetical to self and hostile toward others, that is at the core of a patient's self-limitations and self-defeating actions. The voice varies along a continuum of intensity ranging from mild self-criticism to angry self-attacks and even suicidal thoughts. Self-destructive behavior similarly exists on a continuum ranging from self-denial to accident proneness, drug abuse, alcoholism, and other self defeating behaviors, culminating in actual bodily harm. The two processes, cognitive and behavioral, parallel each other, and suicide represents the acting out of the extreme end of the continuum. The authors provide a chart depicting the levels of increasing suicidal intent along the continuum. The chart identifies specific negative thoughts and injunctions typically reported by persons who attempt suicide, neurotic patients, and "normal" subjects. Understanding where an individual can be placed on the continuum of self destructive thoughts and actions can assist clinicians in their diagnoses and help pinpoint those students who are more at risk for suicide. PMID- 2312940 TI - The effect of student residence on food choice. AB - This study assessed the effect of student residence on food choices and dietary practices of students enrolled in an undergraduate nutrition class at Washington State University. We compared food consumption patterns of students living on campus, off campus, and in Greek housing. We also identified differences between men and women in food consumption and dietary practices. The results suggested that students' residence and sex may influence food choice and dietary practices. Significant differences in food choice related to students' residence were found for 8 of the 27 variables included on a food frequency list. Differences in the consumption of fresh fruits and vegetables, beer, fish, unsweetened cereal, white bread, and cookies were identified. In addition, students who lived in Greek housing were found to skip meals less frequently than other students, and men were found to consume significantly more beer, sugar-sweetened soft drinks, meat, and white bread than women students. Men were also more accurate in their perception of their body weight. PMID- 2312942 TI - Some comments on closing. PMID- 2312941 TI - Use of open-ended essays and computer content analysis to survey college students' knowledge of AIDS. AB - This study used computer content analysis of written essays to explore university students' knowledge and attitudes about AIDS. Because the essays were long, averaging 650 words each, and were on the very general topics of what individuals and society should do about AIDS, it was possible to study a wide variety of subjects. Computer scoring of the essays showed that education and individual changes in sexual behavior were the two methods of prevention mentioned most often. The majority of students accurately identified the most important methods of transmitting the disease. Only one fourth of the respondents discussed casual contact; a majority of those knew that the disease could not be transmitted in this manner. A minority of the students advocated isolating people infected with HIV or marking these individuals in ways that are accessible to others in society. The new computer methods used to analyze the essays offer flexible and efficient procedures for analyzing text on a variety of topics. PMID- 2312943 TI - Results of blood pressure screening in white college students. PMID- 2312944 TI - Consultation between university counseling centers and offices of residence life: an update. PMID- 2312946 TI - Safe and simple needle recapping. PMID- 2312945 TI - A functional TMJ model. PMID- 2312947 TI - Epidemiology of signs and symptoms in temporomandibular disorders: clinical signs in cases and controls. AB - An epidemiologic study of clinical signs and symptoms of temporomandibular disorders (TMD) was conducted with a probability sample of adults enrolled in a major health maintenance organization (HMO). This report presents data from a first wave field examination and interview conducted by trained, calibrated dental hygienist field examiners. Significant gender differences for vertical jaw opening measures were observed but no significant age differences were found for the distribution of clinically relevant findings. Clinic cases showed smaller amounts of vertical range of jaw motion but did not differ from community cases or controls on extent of lateral, protrusive, or retrusive mandibular movements; on classification of occlusion; or on dentally related variables. Clinic cases had more pain during all jaw excursions as well as during muscle and joint palpation. Joint clicking sounds were also observed more frequently in clinic cases. PMID- 2312948 TI - The prevalence and treatment needs of subjects with temporomandibular disorders. AB - A cross-sectional study of prevalence of temporomandibular joint (TMJ) internal derangements, muscle disorders, and associated TM signs and symptoms was completed on 269 female nursing students. The prevalence of specific stages of internal derangements of the TMJ and muscle disorders was estimated, using established diagnostic criteria. The levels of dysfunction and symptomatology associated with each diagnosis were estimated with previously established indexes. When subjects with symptoms were asked if they had previous treatment for a TMJ problem, 6.7% responded positively. When subjects with symptoms who had not had treatment were asked why they had not sought treatment, most responded that it was not a problem or they could live with the symptoms. Thus, most subjects with clinically detectable dysfunction are functioning adequately without significant symptoms and do not need treatment. PMID- 2312949 TI - Multifactorial facial pain--differential diagnosis: a case report. AB - A multidisciplinary algology team was formed to facilitate the diagnosis and treatment of complex head and neck pain disorders. The standard patient evaluation includes a history and physical, surface electromyography, Minnesota Multi-phasic Personality Inventory (MMPI), brief psychiatric interview, dental/occlusal analysis, a postural/musculoskeletal examination; and necessary diagnostic imaging. Clinicians meet in conference after each clinic session. Organic and psychiatric findings are compiled and a differential diagnosis is made. Treatment recommendations are outlined and a review of the evaluation and the therapeutic plan are forwarded to the referring doctor. A typical conference discussion is presented here. PMID- 2312950 TI - Facial pain treated by temporomandibular joint arthroscopy and styloidectomy: report of case. AB - This report describes a patient with both Eagle syndrome and temporomandibular joint (TMJ) internal derangement. The patient's pain was relieved by styloidectomy and arthroscopy. PMID- 2312951 TI - Well-defined radiolucent lesion in the maxillary anterior region. AB - A case of nasopalatine duct cyst is described. Such cysts often remain asymptomatic for lengthy periods and may be discovered during routine radiography. The quiescent nature of this cyst underscores the importance of thorough clinical and radiographic examination before the fabrication of a prosthesis, as such cysts may give rise to acute infection, enlargement, and penetration through the overlying mucosa if not removed before denture insertion. PMID- 2312952 TI - Silent myocardial ischemia: its impact on prognosis. PMID- 2312953 TI - Lack of specificity of new negative U waves for anterior myocardial ischemia as evidenced by intracoronary electrogram during balloon angioplasty. AB - Negative U waves on the surface electrocardiogram are reported to be a specific marker of myocardial disease. In the setting of ischemia, they correlate with stenosis of the left main and left anterior descending coronary arteries. To determine whether U wave changes are unique for anterior ischemia, the development of new U waves on the intracoronary electrogram was correlated with the location and magnitude of ischemia during coronary balloon angioplasty. Recordings were obtained during dilation of 43 vessels in 37 patients. New negative U waves developed during dilation of 12 vessels (7 of the left anterior descending, 4 of the left circumflex and 1 of the right coronary artery). New positive U waves developed during dilation of 18 vessels (12 of the left anterior descending, 3 of the left circumflex and 3 of the right coronary artery). The magnitude of ST segment change was 10.9 +/- 6.7 mm in the presence of a new U wave but only 3.4 +/- 2.8 mm in the absence of a new U wave (p less than 0.001). It is concluded that 1) negative U waves on the intracoronary electrogram are not specific for anterior ischemia; 2) new positive U waves on the intracoronary electrogram are as sensitive as new negative U waves for acute ischemia; 3) the development of a new positive or negative U wave is associated with the magnitude of myocardial ischemia; and 4) the recording of U waves may be related to the proximity of the recording leads to the location of ischemia. PMID- 2312954 TI - The natural history of adults with asymptomatic, hemodynamically significant aortic stenosis. AB - The natural history of asymptomatic, hemodynamically significant, valvular aortic stenosis in adults was documented. Of 471 patients with aortic stenosis identified by Doppler echocardiography (peak systolic flow velocity greater than or equal to 4 m/s) from January 1984 through August 1987, 143 were asymptomatic and had isolated valvular aortic stenosis. Thirty patients underwent aortic valve intervention within 3 months (group 1); the remaining 113 patients did not have an intervention within 3 months (group 2). Follow-up information was available for all patients; the mean duration of follow-up study was 20 months (range 6 to 48). Three cardiac events occurred in the 30 group 1 patients after operation (two deaths, one reoperation). Among the 113 group 2 patients, three had cardiac death presumed to be a result of the aortic stenosis; all three developed symptoms at least 3 months before death. The actuarial probability of remaining free of symptoms of angina, dyspnea or syncope for group 2 was 86% at 1 year and 62% at 2 years. For this group, the 1 and 2 year probabilities of remaining free of cardiac events, including aortic valve intervention or cardiac death, were 93% and 74%, respectively. Of all clinical and echocardiographic variables (group 2), only Doppler flow velocity (p = 0.004) and ejection fraction (p = 0.01) were independent predictors of subsequent cardiac events. Among the 44 patients (groups 1 and 2) with a flow velocity greater than or equal to 4.5 m/s, the relative risk of sustaining a cardiac event (by Cox regression analysis) was 4.9 (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312955 TI - On the natural history of severe aortic stenosis. PMID- 2312956 TI - Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. AB - To assess the presence of viable myocardium salvaged by coronary artery reperfusion, 17 patients with acute anterior myocardial infarction were studied. Each received intravenous thrombolysis within the first 3 h of symptoms and underwent two-dimensional echocardiography before and during dobutamine infusion (10 micrograms/kg per min) 7 +/- 4 days after admission and positron emission tomography 9 +/- 5 days after admission. Echocardiography and positron emission tomography were again performed 9 +/- 7 months later. Six comparable segments specific for the territory of the left anterior descending artery were selected for comparison of the two techniques. Wall thickening was evaluated by using an echocardiographic score index. Segmental perfusion and glucose uptake were measured and normalized to the peak activity. A ratio of glucose uptake to perfusion was calculated for each segment. Concordant interpretation of the two techniques was found in 79% of affected segments for both acute and follow-up studies. Positron emission tomography revealed the presence of viable myocardium in 11 patients (group 1); perfusion was within normal limits in 5 of these (group 1A). Myocardial thickening improved with dobutamine infusion in these five patients, the echocardiographic score index decreasing from 12 +/- 2 at rest to 7.8 +/- 1.3 during dobutamine infusion (p = 0.003). Functional recovery was demonstrated in all five patients (follow-up score index 7.4 +/- 1.7). Six patients exhibited decreased perfusion but an abnormally high glucose to perfusion ratio (group 1B); their score index improved with dobutamine from 14.8 +/- 2.2 to 12 +/- 2.1 (p = 0.05), but late functional recovery was found in only one of the six patients (mean follow-up score index in group 1B 16 +/- 1.7). In the six remaining patients in whom no viable myocardium was detected with positron emission tomography (group 2), the echocardiographic score index did not change with dobutamine (15 +/- 0.9 to 14.7 +/- 0.8, p = NS) and there was no functional recovery (follow-up score index 15.5 +/- 1.0). Echocardiography during dobutamine infusion is a promising method to unmask viable myocardium in acute myocardial infarction. Early recovery of perfusion in the area at risk is associated with a good functional outcome, whereas a high glucose to perfusion ratio indicates jeopardized myocardium that frequently loses viability. PMID- 2312957 TI - Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging. AB - Evaluation of regional myocardial blood flow by conventional scintigraphic techniques is limited to the qualitative assessment of regional tracer distribution. Dynamic imaging with positron emission tomography allows the quantitative delineation of myocardial tracer kinetics and, hence, the measurement of physiologic processes such as myocardial blood flow. To test this hypothesis, positron emission tomographic imaging in combination with N-13 ammonia was performed at rest and after pharmacologically induced vasodilation in seven healthy volunteers. Myocardial and blood time-activity curves derived from regions of interest over the heart and ventricular chamber were fitted using a three compartment model for N-13 ammonia, yielding rate constants for tracer uptake and retention. Myocardial blood flow (K1) averaged 88 +/- 17 ml/min per 100 g at rest and increased to 417 +/- 112 ml/min per 100 g after dipyridamole infusion (0.56 mg/kg) and handgrip exercise. The coronary reserve averaged 4.8 +/ 1.3 and was not significantly different in the septal, anterior and lateral walls of the left ventricle. Blood flow values showed only a minor dependence on the correction for blood metabolites of N-13 ammonia. These data demonstrate that quantification of regional myocardial blood flow is feasible by dynamic positron emission tomographic imaging. The observed coronary flow reserve after dipyridamole is in close agreement with the results obtained by invasive techniques, indicating accurate flow estimates over a wide range. Thus, positron emission tomography may provide accurate and noninvasive definition of the functional significance of coronary artery disease and may allow the improved selection of patients for revascularization. PMID- 2312958 TI - Relation of quantitative coronary lesion measurements to the development of exercise-induced ischemia assessed by exercise echocardiography. AB - To assess the relation of quantitative measures of coronary stenoses to the development of exercise-induced regional wall motion abnormalities, 34 patients with isolated, single vessel coronary artery lesions and normal wall motion at rest underwent exercise echocardiography and quantitative angiography on the same day. Although all 11 patients with a visually estimated stenosis greater than or equal to 75% had an ischemic response and 10 (91%) of 11 patients with a less than or equal to 25% visually estimated stenosis had a normal response by exercise echocardiography, among 12 patients with a visually estimated stenosis of 50%, 6 (50%) had an ischemic response and 6 (50%) had a normal exercise echocardiogram. Quantitative measurements of stenosis severity distinguished patients with ischemic (group 1) from normal (group 2) exercise echocardiographic responses as follows: minimal luminal diameter (mm), group 1 1.0 +/- 0.4 versus group 2 1.7 +/- 0.4, p less than 0.0001; minimal cross-sectional area (mm2), group 1 0.9 +/- 0.6 versus group 2 2.5 +/- 1.1, p less than 0.0001; percent diameter stenosis, group 1 68.3 +/- 14.2 versus group 2 42.2 +/- 12.1, p less than 0.0001; and percent area stenosis, group 1 87.5 +/- 7.8 versus group 2 64.8 +/- 15.9, p less than 0.0001. These data validate the utility of exercise echocardiography by demonstrating that 1) coronary stenosis severity measured by quantitative angiography is closely related to wall motion abnormalities detected by exercise echocardiography, and 2) exercise echocardiography can be used as a noninvasive means to assess the physiologic significance of coronary artery lesions. PMID- 2312959 TI - Exercise echocardiography and quantitative angiography: improved identification of physiologically significant coronary artery stenoses. PMID- 2312960 TI - Influence of alterations in loading produced by lower body negative pressure on aortic blood flow acceleration. AB - The objectives of this study were to evaluate the effects of alterations in loading induced by lower body negative pressure on aortic blood flow velocity and acceleration. Twenty-seven normal men were studied during various levels of lower body negative pressure (0 to -60 mm Hg) during which echocardiographic, Doppler and hormonal measurements were obtained. Lower body negative pressure induced a decrease in left ventricular diastolic diameter from 5.18 +/- 0.08 to 4.41 +/- 0.1 cm (p less than 0.0001) and in left ventricular systolic diameter from 3.33 +/- 0.09 to 2.84 +/- 0.1 cm (p less than 0.0001). Shortening fraction remained unchanged. The decrease in diastolic diameter resulted in a reduction in flow velocity integral from 13.8 +/- 0.8 to 7.5 +/- 0.4 cm (p less than 0.0001) and, therefore, in stroke volume from 89.6 +/- 4.7 to 49.5 +/- 2.8 ml (p less than 0.0001). Heart rate reflexly increased from 62.5 +/- 1.9 to 82.2 +/- 2.3 beats/min (p less than 0.0001) as did systemic vascular resistance from 1,280.8 +/- 69.5 to 1,863.4 +/- 121.4 dyne.s.cm-5 (p less than 0.0001). The increase in heart rate was insufficient to maintain cardiac output, which decreased from 5.53 +/- 0.29 to 3.99 +/- 0.21 liters/min (p less than 0.0001). Systolic, diastolic and mean arterial blood pressure was maintained. The negative pressure resulted in a concomitant significant increase in norepinephrine levels from 1.46 +/- 0.09 to 2.056 +/- 0.2 nmol/liter (p = 0.0019) but no change in plasma epinephrine: 0.845 +/- 0.22 to 0.78 +/- 0.11 nmol/liter (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312962 TI - Mode of onset of atrial fibrillation in the Wolff-Parkinson-White syndrome: how important is the accessory pathway? AB - The mode of onset of 103 episodes of atrial fibrillation lasting greater than or equal to 30 s was studied in 79 patients with the Wolff-Parkinson-White syndrome during electrophysiologic study. No patient had organic heart disease, and 31 had clinical atrial fibrillation before study. These 79 patients were then compared with a control group of 53 patients with Wolff-Parkinson-White syndrome in whom atrial fibrillation could not be induced. Ninety-five of the 103 episodes were technically suitable for analysis. Atrial fibrillation invariably began with rapid atrial tachycardia that became progressively disorganized within 10 to 20 cycles. It was initiated during right atrial stimulation (n = 52), right ventricular stimulation (n = 8), reciprocating tachycardia (n = 33) and spontaneously (n = 2). Most episodes started at a high right atrial site regardless of accessory pathway location, with only 19% of episodes starting at the electrode closest to the accessory pathway. During reciprocating tachycardia (n = 33), either atrial (n = 8) or ventricular (n = 5) extrastimuli initiated atrial fibrillation. Atrial fibrillation started at the accessory pathway site in 6 of 20 episodes occurring spontaneously during reciprocating tachycardia. Patients with atrial fibrillation had a longer PA interval (54 +/- 14 versus 42 +/- 12 ms, p less than 0.0001), shorter atrial functional refractory period (226 +/- 38 versus 240 +/- 30 ms, p = 0.049) and shorter anterograde effective refractory period of the accessory pathway (279 +/- 26 versus 304 +/- 75 ms, p = 0.03). Clinical reciprocating tachycardia was documented with equal frequency in both the atrial fibrillation and control groups (59.5% versus 52.9%, p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312961 TI - Day to day reproducibility of electrically inducible ventricular arrhythmias in survivors of acute myocardial infarction. AB - Day to day reproducibility of the response to programmed ventricular stimulation has not been evaluated in survivors of acute myocardial infarction. Programmed ventricular stimulation was performed prospectively on 2 consecutive days in 56 patients on an average of 12 +/- 5 days (range 7 to 29) after an acute myocardial infarction. No patient had a history of documented or suspected sustained ventricular tachycardia or fibrillation occurring greater than 48 h after infarction. During initial programmed ventricular stimulation, 21 patients had induction of sustained ventricular tachycardia or fibrillation (Group I), and 35 patients had induction of either nonsustained ventricular tachycardia or no ventricular tachycardia (Group II). Repeat programmed ventricular stimulation in Group I patients induced sustained ventricular tachycardia or fibrillation in 16 of 21 patients (reproducibility 76%); the maximal induced response in the other 5 patients was nonsustained ventricular tachycardia in 2 patients and fewer than six repetitive ventricular responses in 3 patients. The day to day reproducibility was significantly higher for inducible sustained ventricular tachycardia of cycle length greater than or equal to 240 ms compared with rapid sustained ventricular tachycardia of cycle length less than 240 ms (100% versus 44%, p less than 0.009) or ventricular fibrillation (100% versus 43%, p less than 0.009). Repeat programmed ventricular stimulation in Group II patients did not induce sustained ventricular arrhythmias in 31 of 35 patients (reproducibility 89%). Thus, in survivors of acute myocardial infarction, inducible slow sustained ventricular tachycardia was a highly reproducible finding, whereas inducibility of rapid sustained ventricular tachycardia and ventricular fibrillation showed a significant day to day variability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312963 TI - Impact of prospective peer review on pacemaker implantation rates in Massachusetts. AB - Preapproval of elective permanent pacemaker insertions in Medicare patients is now mandatory for reimbursement. Of 1,860 requests for approval of an initial pacemaker implant in Massachusetts, 1,494 (80.3%) met strict Medicare guidelines and were approved by a nurse reviewer, and 366 (19.7%) were referred to an independent physician because of a question of appropriateness of indication or type of pacemaker. Only five requests (0.27%) were denied because of an inappropriate indication for pacing. On a second review of these records, an additional eight pacemaker insertions (0.43%) were deemed to have been inappropriately approved. Comparison of the annualized number of pacemaker requests for the study period with those of the 3 years before mandatory approval revealed a reduction of only 3.7%. Thus, contrary to previous findings in other areas of the country, in Massachusetts, inappropriate pacemaker insertions are rare and the effect of the prior approval process is minimal. PMID- 2312964 TI - Role of peer review of pacemaker implantations. PMID- 2312965 TI - Arterial hypertension after orthotopic cardiac transplantation. PMID- 2312966 TI - Contrasting histoarchitecture of calcified leaflets from stenotic bicuspid versus stenotic tricuspid aortic valves. AB - Preliminary findings from clinical trials of percutaneous balloon aortic valvuloplasty and intraoperative debridement of calcific deposits in patients with aortic stenosis have suggested that calcified, congenitally bicuspid aortic valves may be less amenable to these techniques than are calcified tricuspid aortic valves. Accordingly, we evaluated the histoarchitecture of calcific deposits in 30 operatively excised aortic valves. Light microscopic sections taken through the calcified aortic valve leaflets disclosed two principal types of histoarchitecture. In 11 aortic valves nodular calcific deposits were superimposed on an underlying fibrotic aortic valve leaflet (type A); in 17 valves calcific deposits were diffusely distributed throughout the body (spongiosa) of the aortic valve leaflets (type B). Two aortic valves could not be classified histologically. These histologic subtypes were not randomly distributed with regard to gross valvular morphology. All 14 bicuspid valves (100%) were type B; in contrast, 11 (69%) of 16 tricuspid aortic valves were type A, and only 3 (19%) of 16 tricuspid valves were type B (p less than 0.01). Both valves with nonclassifiable histologic features were tricuspid on the basis of gross examination. Thus, the histoarchitectural distribution of calcific deposits is different for bicuspid than for tricuspid stenotic aortic valves. The more diffuse distribution of calcium throughout the body of calcified bicuspid aortic valve leaflets may render these valves less amenable to operative and percutaneous valvuloplasty than are calcified tricuspid aortic valve leaflets on which calcific deposits are typically superimposed in nodular form. PMID- 2312967 TI - Long-term follow-up of amiodarone therapy in the young: continued efficacy, unimpaired growth, moderate side effects. AB - Long-term follow-up data on young patients receiving amiodarone is lacking, especially in relation to growth and late side effects. The records of 95 young patients (mean age 12.4 years; range 3 weeks to 31.5 years) who received amiodarone were reviewed. Minimal follow-up time for those continuing to take amiodarone was 1.5 years; the mean duration of therapy was 2.3 years (maximal 6.5). The mean maintenance dosage was 7.7 (1.5 to 25) mg/kg body weight per day. Initial success (based on symptoms and 24 h electrocardiogram) was achieved in 23 of 34 patients with ventricular tachycardia, in 32 of 33 with atrial flutter and in 21 of 28 patients with supraventricular tachycardia. However, in 7 of 33 patients with atrial flutter, the arrhythmia returned after 6 months. Patient growth continued in the same percentiles achieved before amiodarone in all but eight patients, improving in six and worsening in two with severe underlying disease. Proarrhythmia occurred in three patients: one had torsade de pointes that disappeared when amiodarone administration was stopped; two with severe anatomic heart disease died suddenly during the loading period (one with atrial flutter and one with ventricular tachycardia). Side effects occurred in 28 (29%) of the 95 patients: keratopathy (in 11), abnormal thyroid function test (in 6), chemical hepatitis (in 3), rash (in 3), peripheral neuropathy (in 2), hypertension (in 1) and vomiting (in 1). All side effects disappeared when amiodarone was discontinued or the dose was reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312968 TI - Amiodarone in children: borrowing from the future? PMID- 2312970 TI - Improved cardiac performance secondary to dobutamine: the role of ventricular vascular coupling. PMID- 2312969 TI - Influence of positive inotropic therapy on pulsatile hydraulic load and ventricular-vascular coupling in congestive heart failure. AB - The aortic input impedance spectrum provides a description of the total hydraulic load imposed on the left ventricle and may be used to assess the coupling of the ventricle to the vasculature. The adaptation of the vasculature to positive inotropic intervention was examined in 10 patients with idiopathic dilated cardiomyopathy to test the hypothesis that increased myocardial contractility is matched by complementary changes in aortic impedance that optimize ventricular vascular coupling and maximize power transfer to the circulation. High fidelity intravascular recordings of aortic pressure and flow were obtained at baseline study and during infusion of dobutamine to derive the aortic input impedance spectrum. In eight patients in whom increased staged infusion of dobutamine resulted in a significant increase in stroke volume (22.3 +/- 14.5 ml/beat increase over baseline), the significant (p less than 0.05) increase in the maximum of the first derivative left ventricular pressure pulse (dP/dt) was accompanied by significant decreases in characteristic impedance of the aorta (138 +/- 88 to 92 +/- 44 dyne.s.cm-5) wave reflection index (238 +/- 144 to 109 +/- 59 dyne.s.cm-5), and low frequency moduli of impedance. Effective positive inotropic therapy with dobutamine in the setting of congestive heart failure is accompanied by complementary changes in the aortic impedance spectrum, which represent a matching of impedance to the increased contractile state of the ventricle and facilitation of ventricular-vascular coupling. PMID- 2312971 TI - Combined percutaneous coronary atherectomy and coronary angioplasty: experience in 19 consecutive patients. AB - Among 82 patients undergoing coronary atherectomy, 19 (23%) underwent this procedure in combination with coronary angioplasty. The most frequently involved vessel was the left anterior descending coronary artery. In 11 patients (58%), attempted atherectomy preceded coronary angioplasty. In 6 of the 11, angioplasty was used after the atherectomy catheter could not be positioned across the lesion; 4 patients underwent "rescue" angioplasty after developing vessel occlusion related to atherectomy and 1 patient had an unsatisfactory result of atherectomy. The success rate of the combined intervention was 82% for these 11 patients. In eight patients (42%), atherectomy was performed after initial angioplasty. In four of the eight, atherectomy was a rescue procedure to manage vessel occlusion by thrombus or intimal dissection and was successful in three. In the other four, angioplasty was performed to establish an easier passage for the atherectomy catheter and was successful in three. Thus, the success rate of the combined intervention was 75% for these eight patients. The overall success rate for all 19 patients was 79%; there was one in-hospital death and one non-Q wave infarction, and one patient required immediate coronary artery surgery. Two other patients underwent coronary artery surgery before hospital discharge. Combined intervention with coronary angioplasty and atherectomy seems to be a relatively safe and effective approach in selected patients when either of these procedures alone is unsuccessful or is accompanied by acute coronary complications. PMID- 2312972 TI - Supported "high risk" coronary angioplasty using intraaortic balloon pump counterpulsation. AB - Hemodynamic support may be desirable for selected patients with high risk characteristics undergoing elective coronary angioplasty. Twenty-eight high risk patients were studied with elective intraaortic balloon pump support over a recent 30 month period. Their mean age was 66 years; 10 patients were greater than or equal to 70 years old. Class III or IV angina was present in 23 patients (82%). The mean left ventricular ejection fraction was 24% (range 15% to 50%) and was less than 30% in 25 patients (89%). Three vessel disease was present in 26 patients (93%) and 7 patients had significant left main coronary artery disease. Ninety (96%) of 94 attempts to dilate stenoses were successful, including multivessel angioplasty in 21 patients (75%) and five left main coronary artery dilations. Decreases in systolic blood pressure to less than or equal to 70 mm Hg occurred in 11 patients (39%), but augmented diastolic pressure was greater than or equal to 90 mm Hg at all times. No deaths or myocardial infarctions occurred within 72 h of coronary angioplasty. Vascular complications requiring surgical repair occurred in three patients who had good operative results and no need for transfusions. Thus, intraaortic balloon pump support in patients with high risk features undergoing elective coronary angioplasty appears effective and relatively benign, although definite benefit cannot be proved without a randomized study. Newer techniques, such as in-laboratory cardiopulmonary bypass, must be compared with the results obtained with intraaortic balloon pump support alone. PMID- 2312973 TI - Effect of inotropic and vasodilator therapy on left ventricular diastolic filling in dogs with severe left ventricular dysfunction. AB - Inotropic and vasodilator therapy for congestive heart failure improve left ventricular systolic performance by different mechanisms. However, the nature and extent to which diastolic filling is altered have not been well described. Acute severe left ventricular dysfunction was induced in 21 dogs by severe left ventricular global ischemia produced by left main coronary artery microsphere embolization until left ventricular end-diastolic pressure was greater than or equal to 18 mm Hg. Dobutamine was infused in seven dogs until the peak positive first derivative of left ventricular pressure (dP/dt) increased by greater than or equal to 33%. Nitroprusside was infused in seven dogs until left ventricular end-diastolic pressure was less than 15 mm Hg. Seven dogs were observed for 1 h after the induction of acute severe left ventricular dysfunction and served as the control group. In all groups of dogs, severe left ventricular dysfunction resulted in left ventricular dilation, reduction in area ejection fraction, elevation of left ventricular end-diastolic pressure and an early redistribution of diastolic filling (increased 1/3 and 1/2 filling fractions) despite a markedly abnormal time constant of relaxation. No changes were noted in any variable after 1 h of observation in the seven control dogs. Nitroprusside reduced left ventricular size and filling pressure, increased cardiac output, improved relaxation and redistributed diastolic filling to later in diastole as characterized by a reduced 1/3 filling fraction (19.4 +/- 7.4% versus 51.4 +/- 10%, p less than 0.001). The pressure-area curve was shifted downward and leftward.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312974 TI - Influence of orifice geometry and flow rate on effective valve area: an in vitro study. AB - Fluid dynamics suggests that orifice geometry is a determinant of discharge properties and, therefore, should influence empiric constants in formulas (such as the Gorlin formula) to calculate stenotic valve area. An in vitro study utilizing a model of transmitral flow was conducted to investigate how the discharge coefficient changes with 1) orifice eccentricity (ratio of long to short diameter), 2) absolute area, 3) the presence of a nozzle-like inlet, and 4) varying flow. Twenty-three orifices with areas varying between 0.3 and 2.5 cm2 and eccentricities from 1:1, or circular, to 5:1, or elliptic, were tested. The calculated discharge coefficients ranged between 0.675 and 0.93. For a given area, the discharge coefficient decreased by a mean value (+/- SD) of 5.5 +/- 1.3% between circular orifices and 5:1 ellipses. Discharge coefficients increased by a mean of 8.9 +/- 3.5% from 0.3 to 2.5 cm2 area within each eccentricity class. A gradually tapering inlet (nozzle) raised the discharge coefficient by 8.8 +/- 3.9%, leading to a discharge coefficient between 0.81 and 0.93 for round orifices. The discharge coefficient did not change appreciably with flow. The concept of the discharge coefficient and its role in assessing restrictive orifices in general by hydraulic formulas (for example, the Gorlin and pressure half-time calculations) are discussed. PMID- 2312975 TI - Further reconciliation between pathoanatomy and pathophysiology of stenotic cardiac valves. PMID- 2312976 TI - Sudden death due to isolated acute infarction of the His bundle. AB - A 29 year old black man considered to be in good health died suddenly and unexpectedly. At postmortem examination there were no significant gross abnormalities, all drug screens were normal and sicklemia was not present. Special studies of the cardiac conduction system demonstrated isolated acute infarction of the His bundle, with no similar evidence of myocardial infarction anywhere else in the heart. The atrioventricular (AV) node artery was moderately narrowed, but its branch supplying the His bundle was occluded greater than 95% by focal fibromuscular dysplasia. There were no other significant coronary lesions or other abnormalities in the heart. PMID- 2312977 TI - Benefiting through strategic alliances. PMID- 2312978 TI - Myocardial Infarction Triage and Intervention Project--phase I: patient characteristics and feasibility of prehospital initiation of thrombolytic therapy. AB - Prehospital initiation of thrombolytic therapy by paramedics, if both feasible and safe, could considerably reduce the time to treatment and possibly decrease the extent of myocardial necrosis in patients with acute coronary thrombosis. Preliminary to a trial of such a treatment strategy, paramedics evaluated the characteristics of 2,472 patients with chest pain of presumed cardiac origin; 677 (27%) had suitable clinical findings consistent with possible acute myocardial infarction and no apparent risk of complication for potential thrombolytic drug treatment. Electrocardiograms (ECGs) of 522 of the 677 patients were transmitted by cellular telephone to a base station physician; 107 (21%) of the tracings showed evidence of ST segment elevation. Of the total 2,472 patients, 453 developed evidence of acute myocardial infarction in the hospital; 163 (36%) of the 453 had met the strict prehospital screening history and examination criteria and 105 (23.9%) showed ST elevation on the ECG and, thus, would have been suitable candidates for prehospital thrombolytic treatment if it had been available. The average time from the onset of chest pain to prehospital diagnosis was 72 +/- 52 min (median 52); this was 73 +/- 44 min (median 62) earlier than the time when thrombolytic treatment was later started in the hospital. Paramedic selection of appropriate patients for potential prehospital initiation of thrombolytic treatment is feasible with use of a directed checklist and cellular transmitted ECG and saves time. This strategy may reduce the extent and complications of infarction compared with results that can be achieved in a hospital setting. PMID- 2312979 TI - At home thrombolysis. PMID- 2312980 TI - Syncope in hypertrophic cardiomyopathy: multivariate analysis of prognostic determinants. AB - Twenty-nine consecutive patients with symptomatic hypertrophic cardiomyopathy and a mean age of 44.8 +/- 12.2 years (range 21 to 63) underwent complex invasive and noninvasive testing to identify a risk profile for syncope. Clinical, morphologic, electrophysiologic and hemodynamic variables at rest and at a symptom-limited pacing rate were analyzed for a significant association with syncope. Exact stepwise logistic regression analysis identified three variables as significant independent predictors of syncope in hypertrophic cardiomyopathy: 1) age less than 30 years (beta = 4.803; p = 0.0007); 2) left ventricular end diastolic volume index less than 60 ml/m2 (beta = 3.302; p = 0.006); and 3) nonsustained ventricular tachycardia on 72 h ambulatory electrocardiographic monitoring (beta = 2.5909; p = 0.03). The combined occurrence of all three variables had a sensitivity and specificity of 100% in identifying eight patients with syncopal events. Thus, the risk for syncope in hypertrophic cardiomyopathy is high in young patients with the combination of low left ventricular filling volume and episodes of nonsustained ventricular tachycardia. This finding might also explain the mechanism of syncope in hypertrophic cardiomyopathy as low input low output failure induced by a sudden increase in heart rate in the presence of a low filling volume. PMID- 2312981 TI - Signal-averaged electrocardiography in hypertrophic cardiomyopathy. AB - A major goal in the management of patients with hypertrophic cardiomyopathy is the prediction of sudden death. To evaluate the high gain signal-averaged electrocardiogram (ECG) in this setting, 64 patients with hypertrophic cardiomyopathy and 50 age- and gender-matched control subjects were studied. An abnormal signal-averaged ECG was more common in patients than in control subjects: 13 (20%) of 64 patients with hypertrophic cardiomyopathy had abnormalities compared with 2 (4%) of the 50 control subjects (p less than 0.001). There was a significant association between the presence of nonsustained ventricular tachycardia on 48 h ECG Holter monitoring and the presence of an abnormal signal-averaged ECG: 8 (47%) of the 17 patients with nonsustained ventricular tachycardia and 6 (86%) of 7 patients with more than three episodes of nonsustained ventricular tachycardia per 24 h had signal-averaged ECG abnormalities. There was no association between an abnormal signal-averaged ECG and a family history of premature sudden cardiac death, a history of syncope, symptomatic status, maximal left ventricular wall thickness, the presence of systolic anterior motion of the mitral valve or maximal rate of oxygen uptake on exercise. However, of four patients with a history of cardiac arrest, three had an abnormal signal-averaged ECG. Sensitivity was 50%; specificity was 93% and positive predictive accuracy was 77% for the signal-averaged ECG in detecting patients with electrical instability (defined as a history of cardiac arrest or the presence of nonsustained ventricular tachycardia, or both).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312982 TI - Syncope and sudden death in hypertrophic cardiomyopathy. PMID- 2312984 TI - The giant negative T wave revisited ... in hypertrophic cardiomyopathy. PMID- 2312983 TI - Clinical significance of giant negative T waves in hypertrophic cardiomyopathy. AB - To assess the clinical significance of "giant" negative T waves in patients with hypertrophic cardiomyopathy from Western nations, clinical, echocardiographic, radionuclide and 48 h electrocardiographic (ECG) monitoring findings were compared in 27 patients with and 56 patients without giant negative T waves. Patients with giant negative T waves were older at diagnosis (43 +/- 15 versus 32 +/- 14 years, p less than 0.005), had greater ECG voltage (SV1 + RV5 = 57 +/- 20 versus 37 +/- 18 mm, p less than 0.001) and had a more vertical frontal plane axis (38.4 +/- 34 versus 13.4 +/- 45 degrees, p less than 0.05). Left ventricular wall thickness on two-dimensional echocardiography was similar at the mitral valve level (mean 16.5 +/- 4 versus 16.6 +/- 3 cm), but was greater at the papillary muscle level (mean 20.7 +/- 5 versus 17.6 +/- 3 mm, p less than 0.01) and apex (mean 23.3 +/- 5 versus 17.3 +/- 3 mm, p less than 0.001) in patients with giant negative T waves. Fewer patients with giant negative T waves had asymmetric septal hypertrophy (12 [44%] of 27 versus 36 [64%] of 56, p = 0.08) or systolic anterior motion of the mitral valve (4 [14%] of 27 versus 25 [45%] of 56, p less than 0.01), whereas left ventricular end-diastolic (44.1 +/- 6 versus 39.6 +/- 5 mm, p = 0.01) and end-systolic dimensions (27.8 +/- 4 versus 24 +/- 6 mm, p less than 0.05) were greater in this group. Nonsustained ventricular tachycardia was seen on ECG monitoring in 21% of patients in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312985 TI - Success and failure of exercise training after myocardial infarction: is the outcome predictable? AB - One hundred fifty-six patients underwent a 5 week daily exercise training program after recovery from acute myocardial infarction. Outcome was assessed on the basis of exercise testing, integrating the measurements into a single outcome measure consisting of three categories (positive, n = 79; negative, n = 42; no change, n = 35). This composite criterion served as the end point for determining the predictability of a positive (training success) and negative (training failure) outcome. With use of logistic regression analysis, the baseline variables of clinical information, exercise data and psychosocial variables were able to identify patients with training success, as well as patients with failure (correct classification rates 81% and 85%, respectively). The characteristics of patients for whom training was beneficial differed from those of patients with a negative outcome. Work status before infarction was the single most important predictor of success, but it did not determine failure. Psychologic variables (type A behavior, well-being, depression) were important for predicting failure, but not for predicting success. Cardiac state and physical fitness largely determined training success. It is concluded that the physical benefit of exercise training in patients after myocardial infarction is highly predictable. Validation will make it possible to optimally apply exercise training as a therapeutic modality in these patients. PMID- 2312986 TI - Predicting outcome in cardiac rehabilitation. PMID- 2312987 TI - Hemodynamic and metabolic basis of impaired exercise tolerance in patients with severe left ventricular dysfunction. AB - Hemodynamic and metabolic changes were measured at rest and during exercise in 23 patients with chronic heart failure and in 6 control subjects. Exercise was limited by leg fatigue in both groups and capacity was 40% lower in the patients with failure. At rest, comparing patients with control subjects, heart rate and right atrial and pulmonary wedge pressure were higher; cardiac output, stroke volume and work indexes and ejection fraction were lower; mean arterial and right atrial pressure and systemic resistance were similar. During all phases of exercise in patients with heart failure, pulmonary wedge pressure and systemic vascular resistance were higher and pulmonary vascular resistance remained markedly elevated compared with values in control subjects. Cardiac output was lower in the patients with failure, but appeared to have the same physiologic distribution in both groups during exercise. Although arterial-femoral venous oxygen content difference was higher in patients with heart failure, this increase did not compensate for the reduced blood flow. Even though the maximal oxygen consumption was significantly reduced, femoral venous lactate and pH values were higher than values in control subjects, but femoral venous pH was similar in both groups at their respective levels of maximal exercise. Ejection fraction was lower in those with heart failure at rest and did not increase with exercise. Ventilation in relation to oxygen consumption was higher in patients with failure than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312988 TI - Effort intolerance in chronic heart failure: what are we treating? PMID- 2312990 TI - Atopy in subjects with asthma followed to the age of 28 years. AB - The relationship between markers of asthma and atopy was examined in 323 subjects at the age of 28 years who have been followed since the age of 7 years. Hay fever was common in all groups with severe asthma, increasing from 25% of the control group to 67% of the group with the most severe asthma, class V. Eczema was uncommon at this age in all groups. IgE levels, peripheral blood eosinophil counts, and skin reactions were significantly (p less than 0.05) higher in class V than in the control group. Increasing age was associated with a progressive fall in eosinophil counts and an increase in skin reactivity to common allergens. No change in IgE levels was observed from 21 to 28 years. A general relationship between bronchial hyperreactivity and atopic markers was found. However, only the occurrence of hay fever was significantly related to reactivity when account was taken of severity of asthma. The results indicate that the relationship between asthma and atopy observed at earlier reviews continues into adult life and that bronchial hyperreactivity and atopy are not directly linked. PMID- 2312989 TI - Long-term follow-up of patients with silent ischemia during exercise radionuclide angiography. AB - A retrospective 5 year follow-up study was performed in 140 patients with unequivocal ischemia during exercise radionuclide angiography (greater than or equal to 10% decrease in left ventricular ejection fraction or greater than or equal to 5% decrease in ejection fraction together with a distinct regional wall motion abnormality). In 84 patients (60%), ischemia during radionuclide angiography was silent (silent ischemia group), whereas 56 patients experienced angina during the test (symptomatic group). Work load and antianginal medication were similar in both groups. Critical cardiac events (unstable angina, myocardial infarction, cardiac death) occurred in 27% of patients in the silent ischemia group and 16% of those in the symptomatic group (p = NS); however, myocardial infarction or death was more frequent in patients with silent ischemia (22% versus 9%; p less than 0.05). If there was additional exercise-induced ST segment depression, the rate of critical events was further increased (p less than 0.05). The difference in critical cardiac events seemed to be influenced by the higher incidence of revascularization procedures in symptomatic patients, whereas medical therapy had no similar effect. Thus, these findings suggest that patients with documented severe ischemia should undergo left heart catheterization and revascularization irrespective of symptoms to improve their prognosis. PMID- 2312991 TI - The appearance of hypodense eosinophils during interleukin-2 treatment. AB - Based on membrane receptors, metabolic activity, and cell density, human eosinophils (EOSs) are a heterogeneous population of leukocytes. EOS heterogeneity translates into biologic significance, since low density cells can be metabolically more active and thus more capable of causing tissue injury. Efforts to identify mechanisms that lead to the development of hypodense EOSs have found that an in vitro exposure to cytokines reduces cell density and is associated with increased cell activity. Consequently, we evaluated the effect of an in vivo administration of interleukin-2 (IL-2) on the cell counts and density of circulating EOSs in six patients who received IL-2 as cancer biologic-modifier therapy. To determine the pattern of EOS density in relationship to IL-2 treatment, granulocyte suspensions were isolated from peripheral blood and then centrifuged over multiple discontinuous density Percoll gradients. During IL-2 treatment, the percentage of circulating hypodense EOSs increased significantly (p less than 0.01) until nearly all (97.6 +/- 1.6%) EOSs were hypodense (density less than 1.095 gm/ml). Similarly, the absolute blood EOS counts significantly increased throughout treatment. On completion of IL-2 therapy, the EOS counts and density distribution returned to pretreatment values. In contrast, no increase in blood EOS counts was observed in similar patients receiving interferon (gamma or beta) therapy. Our observations support a hypothesis that IL-2, either directly or, more likely, through the generation of other factors, participates in a change in EOS density that may, in turn, establish a subpopulation of cells with altered metabolic activity. PMID- 2312992 TI - IgG subclass antibody production in human serum sickness. AB - The role of IgG-subclass antibodies in the spectrum of immunologic disorders has not yet been fully defined. In an attempt to understand its role in an immune complex-mediated disease, we studied patients who developed serum sickness (SSX) after treatment with an equine-derived immunoglobulin, antithymocyte globulin (ATG), for bone marrow failure. The predominant IgG subclass produced was IgG1, representing nearly 80% of all IgG anti-ATG activity present. The appearance of IgG anti-ATG antibodies and C1q-containing immune complexes was closely correlated with symptoms of SSX. Although other antibody isotypes were present and may have contributed to the patients' symptoms, it is evident that IgG1 is the predominant IgG subclass produced in human SSX caused by a heterologous protein. PMID- 2312993 TI - Allergic Bipolaris sinusitis: clinical and immunopathologic characteristics. AB - Allergic Aspergillus sinusitis was first reported in 1983. We present the first three cases of allergic fungal sinusitis caused by the black fungus Bipolaris spicifera. The patients were young, atopic, and immunocompetent. All three patients demonstrated pansinusitis with nasal polyps and underwent multiple surgical procedures. Pathologic features included a characteristic mucoid exudate containing eosinophils, Charcot-Leyden crystals, and fungal hyphae. In two cases there was bony erosion revealed by computed tomography scan but no histologic evidence of direct fungal invasion into the mucosa or bony trabeculae. Immunologic features, including total eosinophil count, total serum IgE, immediate and late-phase skin response to B. spicifera, serum precipitins, and specific IgE and IgG to B. spicifera, are described. B. spicifera is a previously unrecognized cause of allergic fungal sinusitis that may be an underdiagnosed disorder. This diagnosis should be considered in atopic patients with nasal polyps and pansinusitis unresponsive to conventional medical therapy. Diagnostic criteria include characteristic histologic allergic mucin, culture identification of fungus, positive immediate cutaneous reactivity to fungal extract, positive serum precipitins, and elevated specific IgE and IgG antibodies. PMID- 2312994 TI - Occupational asthma caused by latex in a surgical glove manufacturing plant. AB - A 33-year-old latex glove inspector was diagnosed as having occupational asthma on the basis of peak flow and methacholine-responsiveness changes related to workplace exposure. She had latex sensitivity by skin prick testing. This finding led to a survey of her workplace. Of the 81 workers, 84% completed a questionnaire to assess work-related respiratory symptoms, 79% underwent skin prick testing to latex and six other workplace chemicals, and 62% performed workshift spirometry. Seven workers had spirometric changes consistent with asthma, of whom five had greater than or equal to 15% fall in FEV1 during the workshift. Six of these workers underwent methacholine-challenge testing, and three were found to have a significant improvement in responsiveness to methacholine away from work, suggestive of occupational asthma. Two of these workers had positive skin test responses to latex. Including the index case, 6% of workers who had pulmonary function testing had findings of latex-related occupational asthma. Skin test responses to latex occurred in 11% of workers tested. Our findings suggest that latex should be considered among the causes of occupational asthma. PMID- 2312995 TI - An optimized assay of specific IgE antibodies to reactive dyes and studies of immunologic responses in exposed workers. AB - Methods of assaying reactive dye-specific IgE antibodies were investigated with a RAST. Sera from three patients, occupationally exposed to a reactive dye, Remazol black B (Chemical Abstract registry number 17095-24-8), were used. Directly dyed disks, that is, disks without any carrier protein, resulted in poor and unreliable measures of specific IgE. In contrast, optimized preparation of conjugates between the dye and human serum albumin resulted in efficient binding of specific IgE. The patients' RAST results were strongly positive, whereas sera from 36 exposed workers but without symptoms and sera from unexposed subjects with high levels of total IgE were negative. The hapten and carrier specificity of the IgE antibodies was studied by direct RAST and RAST inhibition. In one patient, the antibodies were principally hapten specific, whereas another patient was found to have antibodies with a high degree of specificity to the carrier. The third patient's antibodies were intermediate between the other two patients' antibodies in this respect, suggesting that antibody specificity is dependent not only on the nature of the hapten but also on individual immune response factors. The study demonstrates that it is important to use an optimized preparation of dye-protein conjugates to elicit reliable results and a high degree of specific IgE binding in the RAST. PMID- 2312996 TI - Asthma mortality in patients treated by differently trained physicians. PMID- 2312997 TI - Relapsing anaphylaxis to bee sting in a patient treated with beta-blocker and Ca blocker. PMID- 2312998 TI - The outcome of CPR initiated in nursing homes. AB - To determine outcomes following attempted cardiopulmonary resuscitation initiated in nursing homes, we retrospectively reviewed ambulance and hospital records for all 705 people aged 65 or over who underwent attempted resuscitation by ambulance crews in 1987 in Baltimore City and Baltimore County. From medic unit encounter forms we noted whether or not the address of origin was a nursing home and to what hospital the person was taken. Hospital records were then examined to determine outcomes: death in the emergency room, death during consequent hospitalization, or live discharge. Complete information was obtained for all 117 nursing-home residents and for 580 of 588 nonresidents. When attempted resuscitation was begun in a nursing home, only two patients survived to hospital discharge, whereas 61 nonresidents (11%) survived after a mean stay of 14 days. Of the 115 nursing-home residents who did not survive to hospital discharge, 102 (89%) were pronounced dead in the emergency room, two (2%) more died within 24 hours of admission, and the remaining 11 (9%) died after an average stay of five days. Of the 519 nonresidents who died before discharge, 433 (83%) were pronounced dead in the emergency room, 16 (3%) died in the first 24 hours, and 70 (14%) lived an average of nine days. One of the two nursing-home residents who survived was an 87-year-old woman who spent 30 days in the hospital and died eight months after returning to the nursing home, demented, cachectic, with a large sacral pressure sore.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2312999 TI - Ventricular ectopy during prolonged ambulatory electrocardiographic monitoring in elderly hypertensive subjects. AB - To examine whether ventricular ectopy in hypertensive older people is associated with age, the hypertensive process, or treatment, a 24-hour ambulatory electrocardiogram recording was obtained in 94 noninstitutionalized subjects aged 60-90 years with isolated hypertension and 136 noninstitutionalized normotensive subjects aged 60-82 years. A significantly higher prevalence of frequent ventricular ectopic beats (VEB greater than 100 per recording) was found in hypertensive and normotensive groups age greater than or equal to 70 years compared to age 60-69 years (44% vs 15%, P less than .01, and 28% vs 9%, P less than 01, respectively). Complex ventricular ectopy was found to be significantly increased only in the hypertensive group greater than or equal to 70 years compared to 60-69 years (53% vs 28%, P less than .05). No significant difference for any type of ventricular ectopy was found between treated and untreated hypertensive subjects. Analysis of variance of frequent ventricular ectopy showed a significant effect of age (P less than .001) but not of hypertension. Multivariate regression analysis with frequent ventricular ectopy as the dependent variable confirmed this relationship. For complex ventricular ectopy, analysis of variance showed a significant effect of hypertension (P less than .001) and age (P less than .05). Multivariate regression analysis confirmed that complex ventricular ectopy was significantly associated with hypertension (P less than .01) and age (P less than .05). In elderly subjects aging alone is associated with increased frequency of ventricular ectopy, whereas complex ventricular ectopy is more significantly related to the hypertensive process than to age. PMID- 2313001 TI - Alcohol intake in the healthy elderly. Changes with age in a cross-sectional and longitudinal study. AB - Several cross-sectional studies have shown a decline in alcohol intake with increasing age. Longitudinal studies have failed to confirm this trend, which suggests that cohort effects may account for the reported decline. To address this, both cross-sectional and longitudinal analyses of alcohol use in 270 healthy elderly persons over a seven-year period (1980-1987) were performed. Alcohol consumption was assessed by three-day diet records. One hundred sixty five subjects (61.1%) remained in the study until 1987; 143 (53%) completed diet records for every year. Longitudinal analysis showed a statistically significant decline in the percent of subjects consuming any alcohol over time (slope = -2% per year; 95% confidence interval -2.8, -1.1%). A cross-sectional analysis of the 1980 data revealed a similar decline in percent drinkers with increasing age (slope = -2.7% per year; 95% confidence interval -4.4, -1.1%). Mean alcohol intake for those who continued to drink did not change over time except among heavy drinkers (consumption of greater than 30 g per day in 1980), who did show a significant decline in mean alcohol intake (P = .02). Thus, in our population the decline in percent of drinkers with age found by a cross-sectional analysis was confirmed in longitudinal analyses, suggesting that this represents a true age related decline rather than a cohort effect. PMID- 2313000 TI - Effects of exercise training in the elderly on the occurrence and time to onset of cardiovascular diagnoses. AB - To examine the long-term effects of aerobic exercise on the occurrence and time to onset of cardiovascular diagnoses, 184 initially healthy older subjects were randomized into either a long-term exercise group (Group A, n = 80), a short-term exercise group (Group B, n = 42), or a contract control group (Group C, n = 62). After completion of two years in the study, data on new cardiovascular diagnoses and time to onset of these diagnoses in each of the three groups were compared. The occurrence rates for new onset diagnoses were as follows: Group A, 2.5%; Group B, 2%; and Group C, 13%; the average time to onset was greatest for the long-term exercisers and shortest for the contact control group (P less than or equal to .02). The results suggest that a regular program of exercise may have cardiovascular benefits for those over 60 years of age. PMID- 2313002 TI - Use of a vacuum tumescence device in the management of impotence. AB - This study evaluated the use of a vacuum tumescence device in the treatment of impotence in older men. Twenty couples with sexual dysfunction due to erectile impotence and who were interested in restoration of sexual function were treated by providing them with both a vacuum tumescence device to engorge the penis and an obstructing band to impede venous return. Nineteen patients established firm to hard erections lasting an average of 16 minutes and were able to have satisfactory coitus with vaginal ejaculation an average of three times per month. The penile-brachial pressure index, supine and after exercise (a measure of the adequacy of penile arterial flow), exhibited a significant increase following six month's use of the vacuum tumescence device. The only significant complications were mild, self-limited hematomas on three occasions of use. Thus in this limited series the vacuum tumescence device provided a well-accepted, relatively inexpensive therapeutic approach to impotence. PMID- 2313003 TI - Validity and reliability of the dementia behavior disturbance scale. AB - Behavioral disturbance is a common and distinctive feature of Alzheimer's disease and other dementias. Existing instruments designed to quantify behavior disturbance among patients with dementia tend to be quite heterogeneous, including many items that do not refer to behavioral disturbance as such, but rather to cognitive, psychological, or somatic symptoms, or functional impairments. A 28-item Dementia Behavior Disturbance (DBD) scale was developed to avoid some of the problems encountered with the older instruments. In two samples of patients with dementia (n = 50 and n = 46), the most common symptoms were repetitive questions, losing or hiding things, lack of interest in daily activities, nocturnal wakefulness, unwarranted accusations, excessive daytime sleeping, and pacing. The coefficient of internal consistency was greater than .80 in both samples, and the correlation between scores obtained from the same subjects at a two-week interval was moderately high (Pearson's correlation coefficient = .71). There was a relatively high correlation between DBD scores and scores on Greene's Behavior and Mood Disturbance scale, and higher DBD scores were associated with increased duration and severity of disease. These preliminary results indicate that the DBD may be a useful and valid measure of one dimension of the dementia syndrome. PMID- 2313004 TI - Psychotropic drug use among caregivers of patients with dementia. AB - The majority of research on "caregiver burden" focuses on mental health consequences. These stresses are associated with psychotropic drug use among some caregivers. The purposes of this paper are to identify the correlates of psychotropic drug use among caregivers of demented older adults and to determine whether or not certain types of psychotropics (ie, antianxiety, antidepressant, and sedative/hypnotic agents) have common or unique correlates. The prevalence of psychotropic drug use among caregivers in the sample (n = 510) is substantially higher than previously reported prevalence rates in the general population and among community-dwelling elderly. Using logistic regression techniques, caregiver characteristics (eg, gender, health, relationship to the patient) rather than severity of the patient's condition emerge as predictors of antianxiety, antidepressant, and sedative/hypnotic use. The caregiver's perception of how well he or she is supported in the caregiving role emerges as an important correlate of psychotropic drug use in general and especially of antidepressant consumption. Results suggest that caregivers are a high-risk group for the development of emotional symptoms such as nervousness, exhaustion, decreased appetite, and difficulty sleeping, symptoms that may or may not constitute a psychiatric disorder. Characteristics of the caregiver, especially aspects of the support system, should be important considerations in decisions to prescribe psychotropic drugs. PMID- 2313005 TI - Theophylline toxicity associated with the administration of ciprofloxacin in a nursing home patient. PMID- 2313006 TI - The US and the UK. An ocean apart? PMID- 2313008 TI - National Institutes of Health Consensus Development Conference on Urinary Incontinence in Adults. Bethesda, Maryland, October 3-5, 1988. Proceedings. PMID- 2313007 TI - Citations to geriatric and gerontologic journals. PMID- 2313009 TI - Urinary incontinence--where do we stand and where do we go from here? PMID- 2313010 TI - Impact of urinary incontinence on health-care costs. PMID- 2313011 TI - Biofeedback-assisted behavioral training for elderly men and women. PMID- 2313012 TI - Vaginal surgery for stress incontinence. PMID- 2313013 TI - Electrical stimulation. PMID- 2313014 TI - Treatment of urinary incontinence in nursing home patients by prompted voiding. PMID- 2313015 TI - Urine-collection devices for use in adults with urinary incontinence. PMID- 2313016 TI - Incontinence in the American home. A survey of 36,500 people. PMID- 2313017 TI - Professional and public education about incontinence. The British experience. PMID- 2313018 TI - Cancer screening in the elderly. PMID- 2313019 TI - Clock drawing and Alzheimer's disease. PMID- 2313020 TI - Eradication of methicillin-resistant Staphylococcus aureus colonization with ciprofloxacin. PMID- 2313021 TI - Boycott Pennsylvania? PMID- 2313022 TI - New day at AMA. PMID- 2313023 TI - Prenatal care: investing in the future. PMID- 2313024 TI - Training issues for a female psychiatric residency cohort. AB - A three-year retrospective study of the training experiences of an all-female psychiatric residency cohort was conducted, using questionnaires and interviews, to understand the perspectives of both the residents and faculty. The study of this cohort provided a forum in which to take a close look at issues for women trainees in psychiatry. Residents reported being more aware of the group's homogeneity than those who interacted with them said they were, and "feminine" group dynamics were described. The residents were concerned about their professional image and were unaware that they were well regarded by male faculty. This study highlights the need for more female role models as well as for more sharing of perceptions during the training of female psychiatric residents. PMID- 2313025 TI - Part-time doctors: reduced working hours for primary care physicians. AB - Women are entering the professional workforce in increasing numbers, and male professionals are more likely than ever to be involved in dual-career families. For primary care physicians the traditional 50-70-hour work week increasingly creates conflict between professional and other personal goals. Many believe that unless physicians work these long hours they will be unable to successfully provide personal, high-quality continuing care to their patients. Long-term career development for physicians who choose nontraditional arrangements has also presented problems. The authors review the literature on part-time work for physicians, then discuss their experiences as part-time family physicians at an academic health center. Various specific strategies are recommended for physicians and institutions considering part-time employment. PMID- 2313026 TI - Beyond prenatal care: a comprehensive vision of reproductive health. AB - The United States has lagged behind other developed nations with respect to infant and maternal mortality. In the past decade, the disparities between races and socioeconomic groups has actually widened. In response, local initiatives have sought to decrease infant mortality by enrolling women into prenatal care programs. These programs have focused solely on pregnancy, despite evidence that access to family planning, abortion, and gynecologic care is necessary to reduce both infant and maternal mortality. These prenatal care initiatives thus miss the opportunity to have an impact on some of the major public health issues facing women. PMID- 2313027 TI - PMS and eosinophilia-myalgia syndrome. PMID- 2313028 TI - Perceptual consequences of a temporal processing deficit in reading disabled children. AB - Recent research suggests that some children who are reading disabled exhibit sensory deficits associated with poor temporal processing. The performance of disabled readers on various perceptual tasks is consistent with a temporal processing deficit hypothesis. Visual masking paradigms were utilized to obtain direct measures of the temporal aspects of processing in normal and disabled readers, and showed that the visual processing of disabled readers is characterized by a longer integration time and a slower processing rate for both simple and word-like stimuli. Image blurring, which reduces the contrast of high spatial frequencies, reestablished normal temporal processing of words in disabled readers. PMID- 2313030 TI - Optometry and literacy. PMID- 2313029 TI - A new visual-verbal saccade test: the development eye movement test (DEM). AB - The use of presently available clinical oculomotor tests of a visual-verbal format are limited because they do not evaluate automaticity of number naming. There is a significant relationship between automaticity of number naming and reading performance. Presented is a new oculomotor test that has a specific method to factor out the consequences of automaticity on oculomotor performance. Normative data for children age 6-13 years is provided, in addition to reliability and validity information. Clinical utilization of this test for diagnosis and management in visually related learning problems is offered. PMID- 2313031 TI - Optometry: a social discipline. PMID- 2313032 TI - Reflections on continuing optometric education. PMID- 2313033 TI - A simple method for isolation of DNA fragments associated with the nuclear lamina in vivo. AB - We describe a simple method for the purification of DNA fragments associated with the nuclear lamina in vivo. Ehrlich ascite tumor cells are first u.v.-irradiated to crosslink DNA to proteins. The nuclear lamina is then isolated and purified by low-speed centrifugation through a cushion of 40% sucrose. The material sedimenting through the created density barrier represents nuclear lamina of a very high purity, free from any DNA fragments except those which were in a crosslinking distance to it in vivo. PMID- 2313034 TI - Application of inverse regression for estimating molecular masses and Stokes radii of globular proteins by gel filtration chromatography. AB - The aim of this paper is to apply inverse regression as a method for treating experimental data obtained from gel filtration chromatography in order to obtain estimates of hydrodynamic parameters of globular proteins with true confidence intervals. The method is illustrated with the determination, using inverse regression, of molecular mass and Stokes radius for four test proteins (aldolase, chymotrypsinogen A, aldehyde oxidase and xanthine oxidase), from experimental data obtained with a Sephacryl S-300 column. A simple personal computer (PC) program written in standard basic, that is useful for this purpose, is included. PMID- 2313035 TI - Coisolation of glutathione peroxidase, catalase and superoxide dismutase from human erythrocytes. AB - Glutathione peroxidase (GSH-Px; glutathione: hydrogen peroxide oxidoreductase; EC 1.11.1.9), catalase (H2O2: H2O2 oxidoreductase; EC 1.11.1.6) and superoxide dismutase (superoxide: superoxide oxidoreductase; EC 1.15.1.1) were coisolated from human erythrocyte lysate by chromatography on DEAE-cellulose. Glutathione peroxidase was separated from superoxide dismutase and catalase by thiol disulfide exchange chromatography and then purified to approximately 90% homogeneity by gel permeation chromatography and dye-ligand affinity chromatography. Catalase and superoxide dismutase were separated from each other and purified further by gel permeation chromatography. Catalase was then purified to approximately 90% homogeneity by ammonium sulfate precipitation and superoxide dismutase was purified to apparent homogeneity by hydrophobic interaction chromatography. The results for glutathione peroxidase represent an improvement of approximately 10-fold in yield and 3-fold in specific activity compared with the established method for the purification of this enzyme. The yields for superoxide dismutase and catalase were high (45 mg and 232 mg, respectively, from 820 ml of washed packed cells), and the specific activities of both enzymes were comparable to values found in the literature. PMID- 2313037 TI - An improved method for purification of L-threonine deaminase from rat liver. AB - L-threonine deaminase was obtained at a high degree of purity from rat liver. Two main steps were added to the previously reported procedure: cryoprecipitation and chromatofocusing (in the presence of a specific KCl concentration). The purification factor was 3,090 and the specific activity 989. The method is very reproducible and convenient. It gives the highest specific activity and the highest degree of purity of the enzyme recorded to date. PMID- 2313036 TI - Relationship between the hydrophobic and hydrophilic molecular parameters of some synthetic nucleosides, determined by means of adsorptive and reversed-phase thin layer chromatography. AB - The adsorption capacity, the specific adsorptive surface, the lipophilicity and the specific hydrophobic surface of 59 natural and synthetic nucleoside derivatives were determined by means of adsorptive chromatography and reversed phase thin-layer chromatography for the future application of these molecular parameters in quantitative structure-activity relationship studies. Stepwise regression analysis and principal component analysis proved that each of the physico-chemical parameters has a different information content, and their application in the design of new bioactive derivatives is therefore justified. PMID- 2313038 TI - Gerontology: the scientific study of aging, past and future. PMID- 2313040 TI - Life span, morphology, and pathology of diet-restricted germ-free and conventional Lobund-Wistar rats. AB - The effect of germ-free life and dietary restriction (DR) on life span and pathology was investigated in isolator housed germ-free (GF) and conventional (CV) Lobund-Wistar rats fed either ad libitum or restricted to 12 grams per day (70% of adult ad libitum intake) of a natural ingredient diet from weaning. The median length of life of ad libitum CV and GF rats was 31.0 and 33.6 months respectively, while DR increased the median length of life of CV and GF rats to 38.6 and 37.8 months respectively. DR reduced the frequency or postponed the occurrence of diseases which eventually lead to death in the Lobund-Wistar rat. This was especially true of prostate adenocarcinoma, prostatitis, and mammary fibroma. The reduced early food intake and smaller body weight of adult GF rats may be the reason ad libitum fed GF rats live slightly longer than their CV counterparts, but GF life was without additional effect on life span when food intake was restricted. PMID- 2313039 TI - Analysis of angiotensin II binding to human platelets: differences in young and old subjects. AB - We examined the binding of radiolabeled angiotensin II (AII) to human platelets to characterize the apparent increase in AII receptors observed in older subjects. At 22 degrees C, the amount of radioactivity associated with platelets from older subjects increased continuously for more than 2 hours. The same amount of radioactivity was displaced by addition of unlabeled AII at 30 min and 60 min. In the presence of phenylarsine oxide, in the cold, or when labeled antagonist was the ligand, binding came to equilibrium by 30 min. High pressure liquid chromatography demonstrated that 125I-AII was the major radioactive compound in the supernatant and platelets after incubation, but the platelets also contained radiolabeled AII fragments. Thus, some degradation accompanied interaction of AII and platelets. Phenylarsine oxide did not prevent degradation of bound AII, suggesting that degradation precedes internalization. On average, maximum binding was greater in older subjects whether platelets were incubated with 125I-AII alone, with 125I-AII and phenylarsine oxide to prevent internalization, or when the competitive inhibitor 125I-sar1,ile8-AII was the radioligand. Variability of binding among subjects also increased with age. Thus, platelets bind, degrade, and internalize AII, and the three processes occur to a greater extent in platelets from some, but not all older subjects. PMID- 2313042 TI - Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. AB - Previous studies have suggested an association between depressed cell-mediated immunity and increased mortality in elderly persons. However, the effects of age and existing disease on this association have not been adequately addressed. We studied the association between cell-mediated immunity and subsequent morbidity and mortality in 273 initially healthy persons 60 years of age and older. In 1979, two tests of cell-mediated immunity were conducted--mitogen stimulation with phytohaemagglutinin, and delayed hypersensitivity skin testing. The study group was followed annually for development of pneumonia, cancer, and death. Anergy was associated with all-cause mortality (hazard ratio of 2.16; 95% confidence interval [1.10,4.28]). When the results were adjusted for age, the resulting hazard ratio was 1.89;[0.94,3.79]. A relationship was also suggested between anergy and cancer mortality although this association was not statistically significant. Response to phytohaemagglutinin was a poorer predictor of mortality than was response to delayed hypersensitivity skin testing. The results show that anergy may be a good indicator of subsequent all-cause mortality, and perhaps cancer mortality, in elderly who lack other indicators of poor health. PMID- 2313041 TI - Constructing an instrument to measure the rate of aging in female pigtailed macaques (Macaca nemestrina). AB - To develop a battery of innocuous tests measuring individual differences in the rate of biological aging, longitudinal data were gathered on 28 biochemical, physiological, and morphological characteristics of 40 adult female pigtailed macaques. The change in each variable over time, i.e., the beta coefficient of linear regression, was calculated for each animal, and a matrix of correlations among the variables was constructed. Eight variables correlated well with the first principal component of the matrix. These variables (rate of fingernail growth, blood lymphocytes, mean corpuscular hemoglobin, immunoglobulin A, and serum sodium, chloride, total protein, and creatinine) represented the best subset of the potential biomarkers analyzed to produce an index covering a range of morphologic and functional systems that change with age. A similar set representing a wider range of systems and measured over a larger fraction of the life span should provide a valid index of an individual's rate of biological aging. PMID- 2313043 TI - Comparison of biomechanics platform measures of balance and videotaped measures of gait with a clinical mobility scale in elderly women. AB - Performance on the clinical mobility index developed by Tinetti (9) was compared with biomechanics platform measures of sway and videotaped measures of gait in a sample of 43 community-dwelling aged women. Area measures of sway, but not velocity, were associated with performance on the mobility index. When standing on one leg with eyes open, the correlation coefficients for radial area per second with the mobility indices ranged from -0.59 to -0.64 (p less than .001). Knee range of motion and stride length correlated with performance on the mobility index. Knee range of motion correlation coefficients ranged from 0.47 to 0.54 (p less than .001), whereas the range was 0.62 to 0.68 (p less than .001) for stride length. These data demonstrate that biomechanics platform measures of sway and videotaped measures of gait are associated with subject performance on a clinical mobility index and may themselves also be predictive of persons susceptible to falling. PMID- 2313044 TI - Diminished submandibular salivary flow in dementia of the Alzheimer type. AB - Dementia of the Alzheimer Type (DAT) is the most common type of dementia among the elderly. Alzheimer's disease is a major public health problem, yet little is known about the potential oral consequences of the disease. Because saliva is believed to be essential for the preservation of oral health and function, salivary gland fluid output was evaluated in a population of essentially healthy patients with early-stage DAT. Unstimulated and stimulated parotid and submandibular salivary gland secretions were collected from 28 nonmedicated and otherwise healthy DAT patients, and 35 age-matched healthy controls. Submandibular saliva flow rates were significantly lower among the patients with DAT compared to controls, while parotid flow rates did not differ. The results suggest a selective impairment in submandibular gland function in essentially healthy patients with early-stage DAT. PMID- 2313045 TI - Two-year incidence, remission, and change patterns of urinary incontinence in noninstitutionalized older adults. AB - In this study, patterns of urinary incontinence, its severity and types were studied by three sequential data collections at annual intervals. The data are from a panel survey of a probability sample of 1,956 noninstitutionalized persons aged 60 and over residing in Washtenaw County, Michigan, who were interviewed in their homes about urine loss. Based on these self-reports, the prevalence of urinary incontinence was 18.9% in men and 37.7% in women. One-year incidence rates of about 20% among women and about 10% among men were found. One-year remission rates were about 12% for women and about 30% for men. When becoming incontinent, respondents were most likely to develop mild incontinence. Those who changed their severity level were most likely to progress from mild to moderate. PMID- 2313046 TI - Selected acoustic characteristics of speech production in very old males. AB - An understanding of the effects of advancing age on speech characteristics is crucial for those who study and serve the older population. The purpose of this study was to obtain a normative data base for the speech production characteristics of a group of very old men. Fourteen veterans 87 to 93 years old served as subjects, producing a total of 40 sentences at a conversational rate. Wide-band (300 Hz) spectrograms were created from high-quality tape recordings. Specified acoustic measures were made (consonant, vowel, and voice-onset time durations; and vowel formant frequencies and trajectory slopes) via digitizer and microcomputer Sonogram Analyzer program. Descriptive analysis of the selected measurements was performed to obtain a profile of speech production behavior for these subjects. Data were also compared to those of the young adult, Parkinson's disease patients, and younger elderly subjects studied by Weismer (1984a) and Weismer, Kimelman, and Gorman (1985). Performance of the older subjects was similar to that of the younger elderly in many cases, but in certain cases bore notable similarities to Parkinsonian speech. Theoretical implications of aging and disease are addressed. PMID- 2313047 TI - Dispositional control beliefs and the consequences of a control-enhancing intervention. AB - Two traditions of research on the concept of control have developed. One tradition involves the experimental manipulation of control, usually with a focus on enhancing control and thus improving adjustment and well-being. The other tradition regards control as a personality or trait variable and has been concerned with the development and validation of scales to measure it. Linking these two traditions would help determine if people differentially react to control-enhancing manipulations because of control predispositions. This study reports on an investigation into this topic. A sample of 209 subjects responded to the Levenson I-E scale and a control-enhancing manipulation (vs placebo contact and no contact control samples) within the context of a longitudinal assessment of stress and mental health in older adults. Variables assessed included personal mastery and mental health. The results showed significant interactions of the trait and manipulated variables. Control enhancement was most effective for those high in control beliefs. Some positive benefits of the placebo contact also were found. Subjects low in control beliefs did not respond strongly to control manipulations, while those high in control did. Directions for additional research are discussed. PMID- 2313048 TI - Effects of contextual integration on recall of pictures by older adults. AB - This study investigated age-related differences in the ability to utilize integrative relationships between target and context as a memory support by directly manipulating the relationship between a target picture and context. We hypothesized that as the active integration required between target and cue increased, age differences would increase. Old and young adults were instructed to remember target pictures, each presented with a pictorial cue. The cue/target relationship was one of three types: categorically related (high integration condition), visually interacting (high integration condition), or unrelated and noninteracting (low integration condition). Cued recall of the targets was tested. The results indicated that the poorly integrated target-context relationship produced the largest age difference, supporting the integration hypothesis. PMID- 2313049 TI - Cognitive deterioration in Alzheimer's disease: behavioral and health factors. AB - Alzheimer's disease is characterized by progressive cognitive decline. However, little is known about the "typical" rate of decline, the degree of individual heterogeneity evident in decline, or the types of factors that influence such decline. This study investigated these questions in a sample of 106 patients with Alzheimer's disease, assessed at 1-5 points in time, spanning up to three years. At each time point, the Mini-Mental State Exam, a measure of global cognitive function, was administered to all patients. Measures of behavioral disturbance (including the presence/absence of hallucinations, depression, incontinence, wandering, and agitation), health status (including presence/absence of neurological, cardiovascular, and other diseases), and descriptive information (such as gender, age at time of onset, and duration of deficits) were obtained at entry into the study. A two-stage random effects regression model was fit to the data and then used to assess the effect of these behavioral, health, and descriptive measures on the rate of decline. Results indicate that the rate of cognitive decline in Alzheimer's disease is quite variable. Patients with various health and behavioral problems declined at a rate between 1.4 and 5 times faster than patients without such problems. Alcohol abuse, additional neurological disease, and agitation were significantly related to rate of decline. Overall number of problems was not. The association of these problems with accelerated decline may have prognostic and treatment implications. PMID- 2313051 TI - Comparison of two cognitive bedside screening instruments in nursing home residents: a factor analytic study. AB - The Mini-Mental State Examination (MMSE) and the Blessed Orientation-Memory Concentration test (BOMC) were each administered to 110 nursing home residents. The correlation between the MMSE and BOMC's total score was -.79. Maximum likelihood factor analysis revealed a two-factor structure, consisting of memory attention and verbal-comprehension factors that were highly correlated (.69). The results suggest that the somewhat longer MMSE may be preferred for bedside mental status testing, as it clearly measures an additional dimension of cognitive ability, while the BOMC is primarily a unidimensional test. The theoretical and clinical implications of bedside mental status testing of elderly patients are discussed. PMID- 2313050 TI - Chronic pain in old and young patients: differences appear less important than similarities. AB - Two studies compared physical and psychosocial characteristics of elderly and younger chronic pain patients. No age differences were found during intake for the number of physical coping strategies. Elderly patients named fewer cognitive strategies. No age differences were detected in the percentage of patients offered treatment, who agreed to enter treatment, or who completed treatment. Although older patients more frequently had abnormal physical findings, there were no significant differences on measures of self-reported activity, pain severity, life interference, emotional or worry reactions in response to pain. Both age groups had comparable scores on measures of social support and perceptions of how others react to their pain. The present research suggests that there are relatively few factors distinguishing pain patients based on age. Moreover, age should not be a significant factor to consider when offering patients multidisciplinary treatment for chronic pain that focuses on psychological as well as physical modalities. PMID- 2313052 TI - Relationship classification using grade of membership analysis: a typology of sibling relationships in later life. AB - The results of a comparison of two typologies of sibling relationships in old age are reported. Both analyses rely on the same data collected in individual interviews with adults over the age of 65. The first typology was constructed using constant comparative analysis; the second relied on the grade of membership (GOM) technique. This is the first time GOM has been used to create a taxonomy of human relationships based on psychosocial variables. The two typologies are compared in terms of number of types generated, the characteristics of each type, factors influencing typological construction, and the utility of empirical results. Implications for additional use of the GOM technique to study late-life sibling relations are discussed. PMID- 2313053 TI - Appropriateness of composites in structural equation models. AB - The appropriateness of using composites instead of multiple indicators in a structural model of physical health was evaluated. Liang's (1986) specification of self-reported physical health is a relatively complex multiple indicators model which may not be practical in actual application. To simplify this formulation, a two-stage strategy was used. First, reliability was estimated for each composite to fix the measurement error variance and the regression of the composite on the latent variable. Second, the model was reestimated by constraining these parameters. Regression analyses were undertaken to assess the impact of using composites instead of multiple indicators. Parameter estimates for causal linkages and residual error variances based on multiple indicators approach were closely reproduced by using composites, thus providing justification for the proposed strategy. PMID- 2313054 TI - Functional disability of elderly patients with long-term coronary heart disease: a sex-stratified analysis. AB - The survival of elderly women with angina has improved greatly in recent years, but little is known about the functional capacity of these women over the longer duration of their disease. This article analyzes the incidence and determinants of functional disability in a cohort of 1,001 females and males hospitalized with angina or other acute coronary diseases in 1976-77 and followed through 1985. Proportional hazards and logistic models are utilized to examine sex interactions in long-term disability outcomes. Female survivors with angina are shown to be at significantly higher risk for diminished functional capacity when compared to men as well as to women with other heart disease. Thus, the extended survival and higher incidence of angina among elderly women will likely result in an increased societal burden of disablement in the aged population. PMID- 2313056 TI - Relocating adult day care: its impact on persons with dementia. AB - 1. Adult day care centers may be housed in temporary locations as they are being developed or they may be forced to relocate during their existence; this may increase disorientation and other behavior changes in clients. 2. Consistency reduces disorientation and behavioral management difficulties; this can be achieved by low staff turnover, predictable daily routines, and a stable environment. 3. this study concluded that no permanent, harmful effects resulted from the relocation of the day care center. 4. It is important for staff to focus on observing the clients' behaviors and attending to their individual needs when relocating persons with dementia. PMID- 2313057 TI - Assessing urinary incontinence. AB - Nursing assistants are often responsible for the difficult task of accurately observing and recording the incontinence patterns of nursing home residents. Use of the Incontinence Monitoring Record may provide nursing assistants with an easier and more comprehensive method of recording incontinence patterns. Education is an essential component in expecting nursing assistants to consistently and accurately document time, amount, and frequency of incontinence. Satisfactory inter-rater reliability can be attained through use of the Incontinence Monitoring Record with nursing assistants. PMID- 2313055 TI - Predictors of well-being and functioning in older Mexican Americans and Anglos: an eight-year follow-up. AB - Using longitudinal data on older Mexican Americans and Anglos, we examined predictors of functioning and well-being over an eight-year period. Mean declines in measures of activity, health, and psychological well-being were observed in the 254 subjects followed-up, but these declines were not large. Residualized multiple regression analysis showed that Time 2 values of our dependent variables were significantly predicted by their Time 1 values. Age predicted declines in activity levels, while less educated subjects and those reporting lower levels of functional health were more likely to report declines in self-rated health. Less educated subjects were also more likely to report increased psychological distress. Finally, declines in life satisfaction were associated with higher initial levels of psychological distress. These findings are generally in agreement with those found by Palmore et al. (1985) in a different population of older people. PMID- 2313058 TI - Elderly male spouses as caregivers--toward an understanding of their experience. AB - Male caregivers have difficulty assuming personal and household responsibilities; they seem to cope by focusing on the caregiving tasks and projects, establishing daily routines, and carving out their own territory in the home. To facilitate effective interventions, nurses should ascertain the elderly male spouse's meaning of caregiving. This would enable practitioners to foster the caregiver's strengths and provide support in those areas where burden or difficulties are experienced. Husbands as caregivers were more likely than wives to seek the help of formal providers and receive more informal support. Male caregivers tend to not participate in support groups. Before making a referal, nurses should ensure the group is geared to the special needs of the man. PMID- 2313059 TI - Continuous ambulatory peritoneal dialysis therapy for patients with end stage renal disease. AB - CAPD is a method of dialysis that uses the patient's own peritoneal membrane. The semipermeable membrane that lines the abdominal organs and cavity selectively allows the passage of waste products, electrolytes, and fluids. Hemodialysis is an extracorporeal process whereby the patient's blood is withdrawn through a percutaneous needle inserted into a blood vessel. In hemodialysis, the operating principle is a cellophane membrane placed between the patient's blood and wash solution. PMID- 2313060 TI - Environmental interventions in assaultive behavior. AB - Statistical data on patients assaulting other patients are almost non-existent. Collection and analysis of data concerning patient assaults is necessary before effective interventions can be developed. Assaultive behavior can be effected by extrinsic factors such as organizational and environmental structure. Environmental manipulation can change the behaviors of confused, disoriented patients. PMID- 2313061 TI - The therapeutic influence of the environment: a nursing home or a nursing home. PMID- 2313062 TI - Examining helplessness. PMID- 2313063 TI - Continuing education in gerontological nursing. AB - Programs are needed to evaluate staff because more elderly with multiple health care problems are being hospitalized. Current formal training programs do not always have gerontology content based on up-to-date standards. Stimulation exercises give healthy young and middle-aged health-care workers an idea of challenges confronting the elderly with loss of mobility, vision, hearing, or paralysis. A survey of staff nurses indicated that most had difficulty differentiating physical and psychosocial changes attributed to the normal aging process from pathological manifestation. Awareness of the biological, developmental, and psychosocial theories of aging provide health-care workers a greater understanding of rationale for a specific treatment program. PMID- 2313064 TI - [Stage 1 and 2 cancers of the endometrium. Value of the combination of pelvic radiotherapy and curietherapy followed by a total hysterectomy without lymph node removal]. AB - In a retrospective study of 108 patients with stage I-II EC, treated between 1976 and 1983 at CGFL (Dijon), we performed an analysis of the efficacy and tolerance of a treatment approach consisting of external and intracavitary pelvic irradiation followed, 6 weeks later, by hysterectomy without lymph node dissection. Forty-three patients underwent this treatment sequence (G1) and 65 patients (G2) were treated by other modalities (33 intracavitary irradiation and hysterectomy, 27 hysterectomy alone or followed by pelvic irradiation, 5 irradiation alone). The mean follow-up was seven years (5-12). The five year total actuarial survival rate was 82% for G1 and 74% for G2 (p = NS). The five year disease-free survival probability was 80% for G1 and 67% for G2 (p less than 0.05). The post-therapy complications were 2% for G1 (one late post-irradiation complication) and 14% for G2 (one late post-irradiation complication and 6 post surgical complications). Although G1 group has more pejorative clinical and histopathological features (72% T1b or T2 for G1 vs 42% for G2 (p less than 0.005) and 77% grade 2 or 3 for G1 vs 61% for G2 (p = 0.05], the efficacy and tolerance of EIH treatment sequence appear at least comparable to those of G2. These results redefine certain therapeutic aspects of stage I-II endometrial carcinoma which should be considered in future prospective approaches. PMID- 2313065 TI - [Hospital infection in the maternity department. 3 years of surveillance in 9,204 deliveries of which 1,333 were cesarean sections]. AB - Hospital or nosocomial infection, or infection acquired in hospitals, is a health problem in all hospital departments and particularly in the maternity department. We report on a prospective survey of surveillance of hospital-acquired infections both from the mother and the baby's point of view after delivery vaginally or with caesarean carried out at the obstetrical clinic of the Edouard Herriot Hospital in Lyon (France) over three successive years with a series of 9,204 deliveries. The incidence of infection in women who were delivered without caesarean section was 1.37% when urinary tract infections had been excluded but 13% in women who had caesarean sections. Endometritis, skin infections and urinary tract infections were the leading causes. As far as the newborn were concerned, hospital infection ran at about 2.60% and this in the main was due to staphylococcal pustules in the skin. These figures are still too high and prevention should be based on more information given and more care taken by the whole staff of such a hospital. PMID- 2313066 TI - [Future of premature infants of less than 33 weeks gestational age: results of an inquiry undertaken in 1985 in the Paris region]. AB - Improvements in combining obstetrics and neonatology led to a trend to intervene earlier in premature babies born before the 33rd week of gestational age. The enquiry that was carried out in 1985 in the Paris geographical region had as its objective to assess on the one part how many premature deliveries occurred between the 25th and 33rd week of amenorrhea and on the other hand what happened in the short term to the infants born from these pregnancies, i.e., their mortality; and for those who survived, their quality of life. The study was carried out on a representative sample of the deliveries in 1985 in the four departments of the Paris region--Paris and the three departments of the Petite Couronne--where half of all deliveries were assessed. The enquiry covered 53,430 deliveries for which the overall prematurity rate was 4.5%, and those deliveries that occurred before 33 weeks of gestational age constituted 1.0% (539 babies). Twenty children were lost for follow-up after a year. This was 4.9% of the live births and 6.3% of the live children who left the neonatology centres. At 2 years of age, the numbers that were not followed up were eventually 24, which was 5.8% of live births and 7.6% of those that left the centres of neonatology. The results show a very high rate of antepartum mortality but also of mortality during and after labour. Only 379 infants out of the 539 (70%) were transferred into special care baby units. By 1 year of age, the survivors were 57% of the total number of deliveries and 75% of the live births and 82% of those transferred to the special units. As far as concerned those that were live born, the survival rate at the age of 1 year varied considerably according to the duration of the pregnancy. The number of those that survived a pregnancy of less than 27 weeks was low (31%). It was, at 28 weeks, 53%. This is the age where births have to be registered. It reached 87% of the live births that occurred at 32 weeks. One has to point out that there is no statistically significant difference between 27 and 28 weeks of gestation. Whereas there is a significant difference (p less than 0.05) with those delivered at 29 weeks (75%). 80% of those 291 infants that were examined at 1 year of age were considered to be normal as far as psychomotor and sensorial behaviour was concerned.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313067 TI - [Doppler umbilical artery velocimetry during labor in normal pregnancies]. AB - A prospective study using umbilical artery velocimetry was carried out with continuous Doppler wave forms coupled to a spectral analyser (D.F.P.C. Slous) with placement of Pourcelot's placental resistance index in 94 deliveries at term of singleton normal pregnancies. Neither the position of the patient, rupture of the membranes, epidural anaesthesia, oxytocics, Dextrofemine, nor the length of labour, change the placental resistance levels during the delivery. These remain constant and equal R = 0.51 +/- 0.10 (M +/- 2 DS) whatever the appearance of the RCF at the start of labour, during dilatation and during the delivery. We considered term as being between the 38th and the 42nd week of amenorrhea. Our results show that changes in the index of resistance in the umbilical artery do not help in assessing deliveries in normal pregnancies. PMID- 2313068 TI - [The carotid diastolic index: predictive factor for acute fetal distress]. AB - The authors studied 165 patients, 161 of them having been examined at least once for their umbilical diastolic index, uterine diastolic index and carotid diastolic index (CDI) during pregnancy. Four patients have been examined only for the umbilical and carotid indexes. These patients presented either a pathological pregnancy (37% of arterial hypertension; 34% of intrauterine growth retardation; 8% other causes) or previous pathological gestations (21%). Particular emphasis was given to the study of the prediction of CDI with respect to fetal heart rate (FHR) abnormalities or an intrauterine fetal death (IUFD). A mean of 1.4 measurements of CDI per patient were performed, ranging from 1 to 5. The average time lag of the first CDI measurement was of 30 weeks of pregnancy, ranging from 21 to 36.5 weeks. The mean time lag of the children's deliveries was of 35 weeks, ranging from 27 to 40 weeks of pregnancy. The mean time lag of the last CDI measurement with respect to delivery was of 15 days (1 day to 15 weeks). The CDI (CDI = D/S; D = residual diastolic velocity; S = maximal systolic velocity) was considered as pathological when exceeding 22% up to 30 weeks of pregnancy and when exceeding 26% after 30 weeks. 50% of the children born in this series were hypotrophic. When presenting identical umbilical and uterine indexes, the percentage of hypotrophic offspring was the same, whether the carotid index was normal or pathological.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313069 TI - [Menstrual pneumothorax and pelvic endometriosis. Discussion of pathogenesis]. AB - The authors report a new case of menstrual pneumothorax and pelvic endometriosis which was discovered at this time. In this case (because of the presence of lesions suggesting the condition on thoracotomy) the probable mechanism thought to cause this pneumothorax would be the cyclical shedding of pleural endometriotic lesions. The authors review the characteristics of this unusual syndrome and base their review on an analysis of the hundred cases reported in the literature. They show that there are two theories of pathogenicity classically held. The first is the existence of congenital gaps in the diaphragm which allow air to pass into the pleura during the periods, the other is the possibility of endometriotic pleural lesions damaging the cortex of the lung as they shed their cells during the period. PMID- 2313070 TI - [Analysis of 10 cases of pregnancy after renal transplantation]. AB - Renal transplantation has changed completely the fertility of women who had been dialysed. Our study is on 10 pregnancies which we followed up in 7 women who had had renal transplants in the University Hospital of Pitie Salpetriere (Professor Y. Darbois) between 1979 and 1985. All patients were treated by the same technique and the same methods of prevention of rejection of the transplant. The mean interval between the transplant and pregnancy was 53 months. In 3 cases there was hypertension and raised creatinine levels (more than 150 in 3 cases). In 2 cases the two conditions were associated. The prognosis is bad when a raised blood pressure or a change in renal function occurs before pregnancy starts, leading to a real deterioration in renal function during the pregnancy when such function was abnormal before the pregnancy started. As far as the infants were concerned, the most common complication was IUGR (intrauterine growth retardation) which was found in half of all cases. Blood flow studies in these fetuses are particularity interesting. There were two cases of intra-uterine fetal death. The reasons for these were not necessarily connected with the deterioration in renal function. All the deliveries were by caesarean section, for medical reasons in 7 out of 10 cases. The average duration of the pregnancy was 35 weeks of amenorrhoea. As far as the mothers were concerned, they did not have more infections than other women in spite of being immuno-suppressed (this was excluding urinary tract infections).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313071 TI - [Maternal consequences of cesarean delivery. Results of a 4-year follow-up]. AB - This study is of a 4-year follow-up of two groups of mothers, the first having had caesarean operations and the second vaginal deliveries. We have already published studies of the results after delivery, after two months and after one year. The purpose of this 4-year follow-up after delivery is to determine the effects of caesarean operation on the numbers of future pregnancies and their results and to look at the long-term consequences for the physical and psychological health of the mothers. Fifty-eight mothers who had had caesarean operations and fifty mothers as controls replied to a postal questionnaire. The response level was 52%. From the social and the medical point of view there was no significant difference between those who replied and those who did not. The results indicate that mothers who had had a caesarean operation were less likely to have another baby or did so in lower numbers. They further had more difficulty in conceiving another pregnancy than did the control mothers (the differences were not statistically significant). After four years they were often more tired than the others, apart from objective medical and social differences. The use of health services was not linked to the method of delivery, but 9% of women who had had a caesarean consulted a psychiatrist in the last three years but none of the controls did. The replies show that caesarean section contributed to or re-awoke a labile psychological state. The data do not make it possible for us to say that women who had had a caesarean operation had particular psychological characteristics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313072 TI - Episodes in the institutionalization of medical sociology: a personal view. PMID- 2313073 TI - Situational determinants of coping and coping effectiveness. AB - This study contributes to the growing body of research on situational determinants of coping. Based on a general population sample of 1556 married men and women, it goes beyond previous efforts in two ways. First, it presents the first large-scale analysis of situational determinants of coping effectiveness in response to a wide variety of stressful life events and chronic difficulties. This analysis documents that previous aggregate analyses overlooked a number of specifications which, when observed, provide insights into the mechanisms of coping effectiveness. Second, it assesses the importance of two empirically generated multivariate coping profiles, passivity and versatility. The study's findings suggest that these profiles are associated significantly with adjustment to stress, that these associations differ across situations, and that they help to interpret the effects of separate coping strategies. PMID- 2313074 TI - Free enterprise, professional ideology, and self-interest: an analysis of resistance by Canadian physicians to universal health insurance. AB - Under Canada's universal health care system, physicians are remunerated through government-run health insurance plans; a private market for physicians' services is virtually nonexistent. A proposal to ban the practice of extra-billing, whereby some physicians billed patients for amounts over and above insured rates, met with physicians' opposition. The particular constellation of legislative, social, and political events that followed the proposed ban presented a unique opportunity to explore the nature of the medical profession's resistance to encroachment on professional autonomy. The results of this survey of physicians in four specialties (N = 313) in metropolitan Toronto suggest that resistance to universal health insurance is complex; it involves a prevailing social ideology among physicians, which happens to be antiwelfare and conservative generally, entangled with economic self-interest and a specific set of beliefs about medical practice and physicians' rights and privileges. PMID- 2313075 TI - Medicalization as professional process: postwar trends in pediatrics. AB - In the late 1950s American pediatricians began to place increased emphasis on psychosocial and behavioral issues in medical training and research. An intraprofessional movement for psychosocial pediatrics led to alterations in the specialty's stated jurisdiction. One explanation for the movement's origins is that demand for treating sick children was eroding; primary-care providers took up the delivery of behavioral services to avoid extinction. This paper shows that routinization of work, not market decline, preceded psychosocial pediatrics. Academicians rather than community practitioners spearheaded boundary expansion. The movement's major consequence appears to be a new division of labor between pediatricians and other health care professionals rather than increased pediatric treatment of children's psychosocial disorders. PMID- 2313076 TI - Social support and outcome in teenage pregnancy. AB - This paper presents information on the role and significance of social support for the occurrence of health and birth problems among adolescent mothers and their babies. Pregnant teenagers (N = 268) were interviewed during the course of pregnancy and again approximately four weeks after delivery, and hospital records were abstracted. The significance of family support, friend support, and partner support, assessed during the pregnancy, were examined in relation to infant and mother outcomes assessed at or after the birth. Infant outcome was indexed by birth weight, with gestational age controlled; mother outcome in terms of psychological adaptation was indexed by depressive symptomatology among adolescent mothers. Socioeconomic background was found to influence relationships between social support and both infant and mother outcomes. PMID- 2313077 TI - Developmental variation in the context of marijuana initiation among adolescents. AB - A longitudinal sample of 3,454 secondary school students is used to examine the variations in the contexts of marijuana initiation which may be attributable to developmental changes during adolescence. Concepts representing the context of initiation include attachments to parents and peers, exposures to drug-related attitudes of parents and peers and behaviors of peers, and the decision-making process, which involves the weighing of expected costs and benefits of use. Measures representing these concepts are included in logistic regression models predicting initiation. Regression parameters are compared for students in the sixth, seventh, and eighth grades. Results show that only parental attachment measures influence initiation for the youngest group; a mix of parental and peer attachment and peer exposure measures affects initiation for the middle group; and only measures of peer attachment and exposure and of the relative importance of the costs of use predict initiation for the oldest group. The results suggest that developmental factors do influence the context of marijuana initiation. PMID- 2313078 TI - Control or defense? Depression and the sense of control over good and bad outcomes. AB - Defense theory holds that defensive illusions guard well-being. People supposedly are least depressed if they claim responsibility for good outcomes and deny responsibility for bad ones. Control theory states that active, effective problem solving builds well-being; thus a sense of personal control and responsibility for both success and failure is associated with low levels of depression. Which theory is right? Regression analyses of the self-reports of 809 randomly selected Illinois residents show that a sense of responsibility for both successes and failures (instrumentalism) is associated with low levels of depression. There is no measurable benefit from claiming responsibility for the good things while denying responsibility for the bad (self-defense). Depression is associated with not feeling in control of good outcomes, or of bad outcomes, or of both. The sense of control reflects the reality of social and economic status. It explains part of the relationship between status and depression. We infer that defensive illusions are no substitute for genuine control. PMID- 2313079 TI - Depression among the homeless. AB - Very little is known about one of the most common mental health problems facing the homeless: high levels of depressive symptomatology. This paper explains variation in the prevalence of depressive symptoms (CES-D) for a random sample of 150 shelter- and street-based homeless persons in the Birmingham metropolitan area. Fifty-nine percent of the sample show the signs of "probable clinical caseness"; yet there is significant variation in the level of symptomatology. A modified version of the social resources model explains 31 percent of the variation in CES-D scores. Although psychological resources play an important role in the distress outcome, as predicted, social supports are found to have limited impact on depression. Life circumstances have significant direct effects on depression. Persons with previous histories of mental illness and with extensive life event histories are more susceptible to distress. Younger persons, the chronically homeless, the street-based homeless, the sick, and the less educated are also more likely to experience depression. This study suggests the importance of understanding homelessness both as a psychological condition and as a complex set of life circumstances and physical deprivations. PMID- 2313080 TI - Prevalence of viral hepatitis B surface antigen among syphilitic patients: a serological screening survey. PMID- 2313081 TI - Contributions of epidemiology to quality assessment and monitoring. PMID- 2313082 TI - Nosocomial infection caused by Xanthomonas maltophilia: a case-control study of predisposing factors. AB - Factors predisposing to clinically significant nosocomial infection with Xanthomonas maltophilia were examined in a matched case-control study using multivariate techniques. Sixteen cases occurred among cancer patients in a six month period, including an apparent cluster of three cases in an intensive care unit. These infections were unusually serious; eight patients had disseminated infection caused by X maltophilia and six died as a result of their infections. Among the 64 factors that were examined, therapy with broad-spectrum antibiotics and central venous catheterization were found to significantly increase susceptibility to infection. Therapy with imipenem was more than ten times more frequent among cases than among controls (p less than .001). All fatal infections occurred in patients who had received imipenem, including two patients who died before the organism could be identified and appropriate therapy instituted. Infection with X maltophilia should be suspected in patients who develop superinfection while receiving imipenem, and prompt therapy should be instituted to improve chances of survival. Because a common environmental source of X maltophilia was not identified, further study is necessary to determine specific preventive measures. PMID- 2313083 TI - Alcohol for surgical scrubbing? AB - To test the effects of four surgical scrub products on colonizing hand flora, 60 healthy adult volunteers were assigned by block randomization (12 subjects per group) to use one of the following formulations: 70% ethyl alcohol with 0.5% chlorhexidine gluconate (ALC); a liquid detergent base containing 1% triclosan (TRI); a liquid detergent base containing 4% chlorhexidine gluconate (CHG); a liquid detergent base containing 7.5% povidone-iodine (PI); or a nonantimicrobial liquid soap (control). Using standard protocol, subjects performed a surgical scrub daily for five consecutive days. Hand cultures were obtained at baseline and on test days 1 and 5 immediately after the scrub and following four hours of gloving. After the first and last scrubs, ALC, CHG and PI resulted in significant reductions in colonizing flora when compared to the control. Additionally, by day 5 ALC was associated with an almost 3-log reduction as compared to an approximate 1.5-log reduction for CHG and PI and less than a 1-log reduction of TRI and the control (p = .009). After four hours of gloving on both days 1 and 5, microbial counts on hands of subjects using ALC, TRI and CHG were significantly lower than counts for the control (p less than .001), whereas there was no significant difference in counts between the PI and control groups (p = .41). Skin assessment by study subjects rated products from least to most harsh as follows: control, TRI, CHG, ALC and PI p = .00001). It was concluded that ALC could be an efficacious and acceptable alternative for surgical scrubbing. PMID- 2313084 TI - Brief report: the utilization of influencing tactics for the implementation of infection control policies. PMID- 2313085 TI - Emporiatrics: the study of diseases in travelers. AB - Travel to developing countries is exhilarating and, for the most part, safe. However, the unwary traveler may encounter unexpected tropical diseases, many of which are preventable. Additionally, infected travelers may return with exotic diseases that pose special problems for ICPs. PMID- 2313086 TI - History of medicine. PMID- 2313088 TI - Evidence for idiotypic- and antiidiotypic B-B cellular interaction with the use of cloned antiidiotypic B cell line. AB - Immunization of BALB/c mice with MOPC104E myeloma protein induces antiidiotypic B lymphocytes that have Id-specific enhancing activity on antibody production. The B-B cell interaction was restricted to both Igh and class II MHC. However, anti Thy-1 and C-treated splenic B cells were maintained for more than 1 y in a mixture of Con A-stimulated splenocyte culture supernatant and synthetic medium. In applying the long term culture method, we have established a cloned B cell line named B19-1d, B19-1d cells are specific to MOPC104E or J558 cross-reactive Id and they express surface mu, lambda but no Ly-1. B19-1d do not spontaneously secrete Ig but produce them upon stimulation with bacterial LPS. The effect of B19-1d cell line on idiotypic antibody production was tested. Addition of only 10 to 100 B19-1d cells into dextran-immune B cell culture greatly enhanced the Id+ antidextran antibody responses. On the contrary, the antidextran antibody production was suppressed by the higher doses of B19-1d cells. The effective cooperation between dextran-immune B cells and B19-1d cloned B cells was restricted to class II MHC. The role of idiotypic- and antiidiotypic B-B cell interaction in immune regulation and repertoire generation was suggested. PMID- 2313087 TI - Ion channel blockers inhibit B cell activation at a precise stage of the G1 phase of the cell cycle. Possible involvement of K+ channels. AB - Lymphocytes express voltage-activated K+ channels in their membrane. Combining the patch-clamp techniques of recording with immunological methods, we have analyzed the expression and the involvement of these channels during defined steps of LPS-induced B cell activation. We show that the number of K+ channels increased strongly when B cells entered in the G1 phase of the cell cycle. The involvement of ion channels in B cell proliferation was assessed using channel blockers that inhibit the K+ current. It was first found that TEA, but not TMA, quinine and verapamil totally suppressed both K+ current and DNA synthesis by stimulated lymphocytes as measured by [3H]TdR uptake or propiedium iodide staining. The drugs affected neither the induction by LPS of activation markers such as Ag of the murine class II MHC and type II receptor for the Fc region of IgG nor the initial cell enlargement that occur early during activation. These data indicate that functional K+ channels are not essential for the transition from the G0 to the G1 phases. In contrast, the same channel antagonists blocked the induction of transferrin receptor expression, characteristic of the final stages of G1. These drugs acted on cells already in G1, because their addition 30 h after LPS still suppressed DNA synthesis, and because they inhibited the proliferation of purified B cell blasts. The effect of tetraethylammonium was reversible, a lag period of 12 h occurring before the cells start DNA synthesis after drug removal. Taken together, these data demonstrate that the proliferation of LPS-stimulated B cells requires functional ion channels at a critical period in the G1 phase, taking place before transferrin receptor expression and the entry into the S phase. The involvement of voltage dependent K+ channels at this particular point is suggested by the parallel effects of the drugs used on K+ currents and DNA synthesis. PMID- 2313089 TI - Molecular requirements for T cell activation by the staphylococcal toxic shock syndrome toxin-1. AB - The activation of Ag-specific, Ia molecule-restricted, TCR V beta 3+ T cell clones by staphylococcal toxic shock syndrome toxin-1 (TSST-1), was investigated. The results show that although Ag- and TSST-1-induced activation of T cell clones both require TCR expression and similar biologic activation signals, the Ia molecule requirement for TSST-1 recognition was much less stringent than that observed for antigenic peptide recognition. In addition, T cell clones recognized TSST-1 without processing by APC. These results suggest that the ability of TSST 1 to polyclonally activate T cells is dependent on TCR recognition of the intact toxin molecule bound to a nonpolymorphic region(s) of the Ia molecule resulting in the same activation events induced by Ag recognition. PMID- 2313091 TI - The nonobese diabetic mouse model. Independent expression of humoral and cell mediated autoimmune features. AB - Nonobese diabetic (NOD) mice present concomitant signs of cell-mediated and humoral autoimmunity. Whereas the involvement of the cell-mediated manifestations in the pathogenesis of diabetes has been clearly demonstrated, the origin and the relevance of the humoral manifestations is still unclear. In the present study, we have tried to determine whether the humoral manifestations observed in NOD mice were secondary to the cell-mediated antiislet reaction, or whether they resulted from an autonomous polyclonal activation of B cells, a possibility suggested by the notorious presence of antilymphocyte antibodies with thymocytotoxic properties, in the serum of old NOD females. To discriminate between the two alternatives, we have followed the titers of thymocytotoxic autoantibodies in aging males and females, as well as in F1 hybrids where the organ-specific disease is recessive, and in back-crossed mice where the susceptibility genes responsible for insulitis and diabetes have segregated. In addition to thymocytotoxic antibodies, we have also screened the sera of these animals for hyperglobulinemia, antiinsulin, and anti-DNA autoantibodies that are classically associated with polyclonal B cell activation in autoimmune strains of mice. The results indicate that these humoral anomalies are clearly disconnected from the occurrence of diabetes and even of insulitis. Lymphocytotoxic antibodies appear several weeks after the onset of insulitis in NOD mice, are not correlated with disease occurrence and have no predictive value for its onset. The humoral manifestations that include, beside thymocytotoxic antibodies, antiinsulin antibodies, hyperglobulinemia, but no anti-DNA antibodies, are found at the same frequency in F1 mice as in parental mice in spite of the fact that the former are practically free of insulitis lesions. These anomalies are also randomly distributed among back-crossed mice independently of the presence and the severity of the organ-specific lesions. Altogether, these results suggest that NOD mice, like other autoimmune strains, suffer from a genetically inherited defect of B cell regulation resulting in the hyperproduction of natural autoantibodies. PMID- 2313090 TI - Recombinant human IL-4 induces IgE and IgG synthesis by normal and atopic donor mononuclear cells. Similar dose response, time course, requirement for T cells, and effect of pokeweed mitogen. AB - Unfractionated human blood mononuclear cells (MNC) from normal and atopic donors cultured in enriched Iscove's modified Dulbecco's medium supplemented with 10% FCS responded similarly to stimulation with purified human rIL-4 (rhIL-4) with respect to the concentration required to induce IgE synthesis and the magnitude and kinetics of the IgE response. The IgE response of MNC was IL-4 dose dependent, increasing linearly with IL-4 concentrations between 0.2 and 2.5 ng/ml and plateauing at concentrations of 5 ng/ml or more. rhIL-4-induced IgE synthesis was first detected at 9 days after stimulation and supernatant IgE concentrations reached a maximum on day 18. rhIL-4 stimulated IgE synthesis by MNC from all donors tested, with peak supernatant IgE concentrations ranging from 3 to 372 ng/ml. The nonatopic group (n = 15) geometric mean peak concentration was 24.0 ng/ml and that of the atopic group (n = 19) was 20.0 ng/ml (p = NS). rhIL-4 also stimulated IgG synthesis by MNC from some (but not all) donors in quantities comparable to those induced by PWM. Maximum supernatant IgG concentrations in responders were found 18 days after stimulation. When PWM was added to the IL-4 stimulated cultures, it completely inhibited rhIL-4-induced IgE and IgG synthesis. rhIL-4 also completely inhibited PWM-induced IgG synthesis. Stimulation of IgE synthesis by rhIL-4 required the presence of T cells. T cell clone supernatants did not support rhIL-4-induced IgE synthesis by B cells. T cells from atopic and nonatopic donors restored rhIL-4-stimulated IgE synthesis by B cells from either source to a similar extent. PMID- 2313092 TI - IL-1 beta is secreted by activated murine macrophages as biologically inactive precursor. AB - IL-1 alpha and IL-beta are distinct cytokines, produced by activated macrophages. The temporal sequence in the processing and secretion as well as the mechanism(s) by which IL-1 is secreted from the cells remain undefined. Here we have studied the production of IL-1 from murine macrophages after stimulation with LPS or Listeria monocytogenes by two distinct methods: i) immunoprecipitation of radio labeled IL-1 peptides from culture supernatants, and ii) determination of IL-1 activity by neutralization with monospecific antisera to either form of IL-1. We confirmed that precursor and mature forms of both IL-1 alpha and IL-1 beta can be detected in the culture supernatants after stimulation of the macrophages with 10 to 20 micrograms LPS/ml but, in addition, we report the novel finding that IL-1 beta is exclusively secreted in its unprocessed precursor form after stimulation of the cells with either 0.5 to 1 microgram LPS/ml or with L. monocytogenes. Exposure of the cells to increasing amounts of LPS led to the appearance of a 20 kDa IL-1 beta peptide in the culture supernatants concomitant with the release of a processing activity for the IL-1 beta precursor. These data therefore suggest that, in a first step, IL-1 beta is secreted as an unprocessed precursor protein that in a second, postsecretory step is cleaved by a LPS-inducible protease, thus generating the 20-kDa IL-1 beta peptide. The latter represents the biologically active IL-1 beta inasmuch as the generation of IL-1 beta activity in the culture supernatants strictly correlated with the appearance of the 20-kDa IL-1 beta peptide. PMID- 2313093 TI - MHC-like molecules in some nonmammalian vertebrates can be detected by some cross reactive xenoantisera. AB - Rabbit antisera raised to human and chicken MHC molecules were used to immunoprecipitate cross-reactive molecules from biosynthetically and cell surface labeled spleen and/or blood cells of representative vertebrate species. Five major points emerged: 1) There were many nonspecific cross-reactions using these techniques, so various criteria were developed to distinguish these from true MHC like molecules. 2) Only very small subpopulations of immunogen-specific antibodies cross-reacted with MHC-like molecules in other nonmammalian species. These subpopulations were different for each species and even within a species, sometimes being so limited as to behave like alloantisera. This led to a very scattered pattern of true cross-reactions that sometimes failed to reflect the properties of the bulk antibody population. 3) Antisera containing antibodies to class II beta- and class I alpha-chains cross-reacted better and more widely than those to B-G, class II alpha and, in general, beta 2-microglobulin. 4) Some cross reactive antibodies were clearly directed to epitopes on the surface of the mature heterodimers, but many seemed to recognize nonlinear cryptic determinants, presumably in the contact regions between the chains. These latter antibodies recognized biosynthetic intermediates and also a variety of unusual cell surface MHC-like molecules present in reptile and amphibian, but absent in the mammal and chicken cells tested. These included E homodimers whose relationship to chicken B G molecules is unknown. 5) MHC-like molecules were identified in a bird, three reptiles, and two amphibians, but no molecules with the expected properties were found with these reagents in any of the fish tested. PMID- 2313094 TI - Binding of the pentamer/hexamer forms of mannan-binding protein to zymosan activates the proenzyme C1r2C1s2 complex, of the classical pathway of complement, without involvement of C1q. AB - The serum lectin, mannan binding protein (MBP), was isolated in a yield of 40 micrograms/liter from pooled normal human serum by affinity chromatography on mannan-Sepharose, followed by gel-filtration and ion-exchange chromatography and finally by passage down an anti-IgM Sepharose column. A rabbit antiserum was prepared against the purified MBP and an enzyme-linked immunoassay developed that used both the specificity of the polyclonal antibody and the Ca+(+)-dependent carbohydrate binding property of MBP. Assay of the sera from 103 blood-donors showed a wide range of MBP levels, ranging from 0 to 870 micrograms/liter. MBP, after interaction with zymosan, caused efficient activation of a C1r2 125I-C1s2 complex that was prepared by incubation of 125I-C1s2 with serum, from a patient with a complete genetic deficiency of C1q, followed by gel-filtration on Sepharose 6B. The purified MBP is composed of a mixture of trimers, tetramers, pentamers, and hexamers of an approximate 90-kDa structural unit as judged by chromatography, SDS-PAGE and electron microscopy studies. Only the molecules in the pentamer/hexamer fraction, which have a similar overall structure to that of C1q, appeared to cause efficient, zymosan-dependent, activation of C1s within the C1r2C1s2 complex. The pentamer/hexamer form of MBP may therefore play an important role in antibody-independent activation of the C system during the early stages of certain infections. PMID- 2313096 TI - Chemotactic factor inactivator interaction with Gc-globulin (vitamin D-binding protein). A mechanism of modulating the chemotactic activity of C5a. AB - Chemotactic factor inactivator (CFI) can decrease the neutrophil chemotactic activity of C5a. Gc-Globulin (GcG) can function as a cochemotaxin for C5a by binding to C5a or C5a des Arg and enhancing its chemotactic potency. We hypothesized that CFI might interact with GcG and thus decrease the chemotactic activity of C5a. CFI was found to markedly inhibit the neutrophil chemotactic activity of partially purified C5a containing GcG (p less than 0.01). Addition of GcG was able to reverse the capacity of CFI to inhibit C5a-directed neutrophil chemotaxis (p less than 0.01). CFI had no significant effect on neutrophil chemotaxis when incubated with C5a depleted of GcG or C5a des Arg. CFI was also able to inhibit the interaction of C5a with GcG adsorbed to plastic. To determine if CFI interacted with GcG, a sandwich ELISA was used. These ELISA tests demonstrated that CFI directly interacted with GcG in a dose-dependent manner that was both heat and pH sensitive. To investigate the possibility of enzymatic degradation of C5a by CFI, CFI preparations were analyzed for carboxypeptidase activity, aminopeptidase activity, and for the capacity to cleave dansylated C5a. No enzymatic activity or cleavage was observed. Furthermore, the direct interaction of CFI with C5a and C5a des Arg was assessed by ELISA tests and column chromatography and no interaction was observed. These results suggest that CFI modulates C5a-directed neutrophil chemotaxis by interacting with GcG and preventing GcG from enhancing the chemotactic potency of C5a. PMID- 2313095 TI - Oxidized low density lipoprotein suppresses the expression of tumor necrosis factor-alpha mRNA in stimulated murine peritoneal macrophages. AB - In the present report we have examined expression of the gene encoding the inflammatory monokine TNF-alpha in murine peritoneal macrophages treated with different forms of low density lipoprotein (LDL). LDL modified by oxidation in vitro is unable to stimulate inflammatory gene expression in peritoneal macrophages. However, treatment of macrophage cultures with oxidized LDL for 6 h or more resulted in a concentration and time-dependent suppression of TNF-alpha mRNA expression induced in response to stimulation with either LPS or maleylated BSA. This suppression was maximal after 12 h of exposure to oxidized LDL and at a concentration of 100 to 200 micrograms LDL cholesterol/ml of culture medium. The suppressive effect was restricted to oxidatively modified LDL as treatment with native LDL or acetylated LDL did not affect TNF-alpha mRNA expression, despite the fact that both acetylated and oxidized LDL lead to intracellular lipid accumulation. The expression of maleyl albumin-stimulated TNF-alpha mRNA expression could be reproduced by lipid extracts of oxidized LDL provided to macrophages at the same cholesterol concentration as from the intact lipoprotein particle. Extracts from native LDL were ineffective. These results suggest that oxidized lipid accumulation in monocytes infiltrating the arterial wall may lead to the suppression of certain inflammatory functions which, in turn, may influence the development of mature atherosclerotic lesions. PMID- 2313097 TI - Secretion by human fibroblasts of monocyte chemoattractant protein-1, the product of gene JE. AB - We recently purified human monocyte chemoattractant protein-1 (MCP-1) from culture fluids of either human glioma cell lines or mitogen-stimulated human peripheral blood mononuclear leukocytes. It has now been shown that MCP-1 is the product of the gene JE, which was first recognized by its expression in fibroblasts stimulated with platelet-derived growth factor (PDGF). We therefore studied secretion of MCP-1 by three human fibroblast cell lines. Monocyte chemotactic activity was found in culture fluids of all three lines after growth to confluence in DMEM-10% FCS, and the amounts secreted per cell were comparable for the three lines. The MRC-5 line was chosen for further study. Monocyte chemotactic activity secretion by confluent MRC-5 cultures continued after a switch to serum-free medium and was not inhibited by anti-PDGF antibody, indicating that secretion may not have been caused by autocrine release of PDGF. When concentrated serum-free MRC-5 culture fluid was injected into an HPLC gel filtration column, only one chemotactic activity peak was observed, which was in the same location as glioma-derived MCP-1. The activity was completely absorbed out by an anti-MCP-1 affinity column, which indicates that all the chemotactic activity in MRC-5 culture fluid was accounted for by MCP-1. PDGF caused a marked increase in chemotactic activity over that found in serum-free culture fluid of MRC-5 or 501T cells. Immunoprecipitation by anti-human MCP-1 showed two bands, corresponding to the two forms of MCP-1 previously described (MCP-1 alpha and beta); and the amounts increased in response to PDGF stimulation. Thus, the reported increase in human fibroblast JE mRNA in response to PDGF-containing serum stimulation is reflected in increased secretion of the MCP-1 gene product. PMID- 2313098 TI - In vitro production of antibody to hepatitis B core and E antigens by peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection. AB - To evaluate the relative immunogenicity of and the mechanism for production of antibody to hepatitis B core (HBc) and hepatitis B e (HBe) Ag, we investigated the in vitro anti-HBc and anti-HBe production by PBMC from 25 patients with chronic active hepatitis (CAH) (15 with HBeAg and 10 with anti-HBe) and 12 ASC (5 with HBeAg and 7 with anti-HBe) in the presence of PWM, rHBcAg, or purified HBeAg. PWM-stimulated culture produced higher titer anti-HBc (mean % inhibition +/- SD = 73 +/- 23%, p less than 0.001) than anti-HBe (34 +/- 17%). HBcAg stimulation elicited greater anti-HBc response (43 +/- 26%, p less than 0.001) than did HBeAg for anti-HBe (26 +/- 12%). Both HBcAg and HBeAg induced equivalent anti-HBe response. Anti-HBc production in response to HBcAg was higher in CAH patients (51 to 55%) than in asymptomatic carriers of hepatitis B surface Ag (22 to 28%) irrespective of their HBeAg/anti-HBe status, but reflecting serum anti HBc value. Similar findings were noted in HBeAg-stimulated anti-HBe production for the two patient groups. In HBeAg- and anti-HBe-positive CAH, HBcAG-stimulated anti-HBc production was similar in T (1.4 x 10(6)) and B (0.6 x 10(6)) cells coculture, and B cells (2 x 10(6)) alone culture. However, in the HBeAg stimulated culture, T plus B cells produced significantly higher titer anti-HBe than B cells alone did. These results indicate that HBcAg has a relatively higher immunogenicity in terms of antibody production as compared to HBeAg. Furthermore, HBcAg was shown to function as a T cell-dependent and -independent Ag, whereas HBeAg is T cell-dependent during chronic hepatitis virus B infection in man. PMID- 2313099 TI - Activation of the complement system during immunotherapy with recombinant IL-2. Relation to the development of side effects. AB - Therapy with high doses of rIL-2 is complicated by the occurrence of hypotensive reactions and the development of a vascular leakage syndrome (VLS). In four patients, who together received seven cycles of high doses of IL-2 (up to 12 x 10(6) U per m2 per day), and who developed these side effects, we observed an unexpected increase in plasma levels of C3a, indicating activation of the complement system. C3a levels markedly increased during IL-2 therapy from 4 nmol/liter (mean level) before therapy to 23 nmol/liter at the end of the cycle. Activation of C3 occurred via the classical pathway inasmuch as C4a levels also increased during therapy. Mean daily C3a levels correlated with signs of the VLS, such as daily weight gain (p less than 0.001) and albumin levels (inverse correlation, p less than 0.001). In five additional patients, who together received seven cycles of lower doses of IL-2 (2 x 10(6) U per m2 per day) and who did not develop a VLS, only moderate increases in C3a levels (up to 13 nmol/liter) were observed. The highest levels at the first day of the regimen (mean: 7 nmol/liter) occurred 8 h after the IL-2 infusion. Thus, administration of IL-2 induces a dose-dependent activation of the complement system in vivo, which appeared to be related to the development of side effects of this therapy, such as the VLS. PMID- 2313100 TI - An improved method for immobilizing IgG antibodies on protein A-agarose. AB - This report describes a modification of a procedure developed by others for crosslinking IgG to protein A which itself is covalently linked to a gel support. Earlier immunoaffinity columns were described as having large antigen-binding capacities and stability under a variety of elution conditions. The present data show that columns constructed with earlier techniques were only partially stable to pH 3.0 buffers, and, as a result, bound less than 20% of the antigen predicted by theory. Modifying parameters of the dimethylpimelimidate crosslinking method led to immunoaffinity columns which did not leak immunoglobulin under low pH elution buffer conditions. The new immunoaffinity absorbants, because of the increased strength of the couple between the antibody and protein A, were capable of binding antigen at over 80% of their theoretical capacity. PMID- 2313101 TI - Detection of adenovirus type41 in stool samples by a latex agglutination method. AB - We have developed a simple agglutination (LA) method for the detection of enteric adenovirus (EAd) in stool samples from infants with acute gastroenteritis. Ad type 41 (Ad41) was detected with high sensitivity and specificity by a slide agglutination test using latex particles coated with antiAd41 antibody (LA antiAd41). The agglutination of LA-antiAd41 with Ad41 on a glass slide was evident macroscopically within 2 min. The sensitivity of the LA method was four times higher than that of the EM method. PMID- 2313102 TI - Serum-manganese-superoxide dismutase: normal values and increased levels in patients with acute myocardial infarction and several malignant diseases determined by an enzyme-linked immunosorbent assay using a monoclonal antibody. AB - An enzyme-linked immunosorbent assay (ELISA) has been developed for human manganese-superoxide dismutase (Mn-SOD), using a specific monoclonal antibody raised against the purified enzyme. The Mn-SOD molecule comprises four identical sub-units and this permitted the development of a symmetrical assay, using the same monoclonal antibody as both capture and detector. The assay offers a specific, sensitive and convenient means of measuring immunoreactive Mn-SOD in human sera. Under optimum conditions, the sensitivity of the assay permits the detection of 2-200 ng of purified Mn-SOD from human liver. The mean serum Mn-SOD levels of normal healthy males and females were 99.8 +/- 24.8 (mean +/- SD) and 88.8 +/- 20.8 (mean +/- SD), respectively. A high level of the enzyme was found in the sera of patients with acute myocardial infarction as well as malignant diseases such as acute myeloid leukemia, primary hepatoma and gastric cancer. This is the first report of an ELISA using a monoclonal antibody specific for a distinct epitope of Mn-SOD. PMID- 2313103 TI - A new radioimmunoassay for the thymic peptide thymulin, and its application for measuring thymulin in blood samples. AB - A new, specific and sensitive radioimmunoassay, using a polyclonal antiserum raised in rabbits, is described for quantitating plasma thymulin. As little as 300 fg thymulin can be measured in one assay tube. The method has been used to measure thymulin in human blood (umbilical vessel blood, 2191 +/- 123 fg/ml; children and adults up to the age of 20 years, 1499 +/- 119 fg/ml; and adults between 21-65 years, 371 +/- 18 fg/ml). There is a highly significant decrease within these three groups (P less than 0.001 by one way analysis of variance). Also plasma thymulin levels were determined in rats (601 +/- 127 fg/ml) and in pooled plasma samples from mice (638 +/- 56 fg/ml). No thymulin was detected in plasma obtained from nude rats, nude mice and thymectomised mice. These results show that the radioimmunoassay described here is a useful quantitative tool for measuring plasma thymulin that will have applications in basic, applied and clinical research. PMID- 2313104 TI - A monoclonal antibody which blocks the function of factor D of human complement. AB - Factor D is an essential enzyme for activation of complement by the alternative pathway (AP). It has been difficult to obtain mouse monoclonal antibodies (Mabs) which block the function of factor D. We have developed a strategy to obtain such Mabs using a double screening procedure of the initial clones. We selected the clone whose supernatant had the lowest level of anti-factor D Ab by ELISA and abolished factor D haemolytic activity. Addition of this Mab to human serum was shown to abolish conversion of C3 by cobra venom factor, haemolysis of rabbit erythrocytes, and activation of C3 and C5 by cuprophane dialysis membranes. PMID- 2313105 TI - A neonatally tolerant mouse model to assess pathogenicity of human autoantibodies. AB - Since certain autoimmune diseases, including myasthenia gravis and pemphigus vulgaris can be reproduced in mice by passive transfer of immunoglobulins from affected patients, we assessed whether this procedure could be optimised. Repeated injections of human IgG into mice during pregnancy induced tolerance to human IgG in the litter, and this persisted for at least 9 months. We show that three different human autoantibodies, to mitochondria, centromere and collagen, were retained in the serum of neonatally tolerized mice, but pathogenic effects of these particular autoantibodies were not demonstrable over the four week time scale of our experiments. However, our model should be applicable to studies on human autoantibodies which might damage the appropriate tissue in a heterologous species. PMID- 2313106 TI - [Comparative study of tubulate enterocystoplasty and low pressure bladder. Apropos of 20 cases]. AB - The goal of this presentation is to report the results on morbidity and continence of 20 consecutive patients who, from January 1985 to December 1988, underwent bladder reconstruction after cystectomy for bladder cancer. In ten cases the neo-bladder was a classic ileocystoplasty and in the ten others it was a "low pressure neo-bladder". We compared the two groups although they were not randomized. There was no stadification difference in tumors nor in clinical status. The clinical results were described. There have been four temporary urinary fistulas in the group of low pressure bladder (LPB), and four in the group of classic ileocystoplasty (CI). In the group of LPB, 7 from 8 patients were completely dry day and night and voided every two for three hours while among the 9 patients with CI, 4 were continent day and night. PMID- 2313107 TI - [Advanced testicular seminoma: treatment of residual masses after chemotherapy. A review of 3 cases]. AB - Based on 3 cases of advanced testicular seminoma classified as stage IIC, the treatment of residual masses after chemotherapy is discussed. The excellent therapeutic response confirmed by histological study of the residual masses, which show a fibrotic or necrotic appearance, allows the adoption of a strategy using imaging techniques: either there is persistence of a gland mass syndrome and resection needs to be carried our or retroperitoneal fibrosis is visualised and careful follow up would appear to be sufficient. PMID- 2313109 TI - [Perirenal hematoma caused by anticoagulant therapy involving a pathologic kidney. Apropos of 2 cases]. AB - The occurrence of a peri-renal hematoma on anticoagulant therapy does not classically indicate underlying renal pathology and has a favorable spontaneous prognosis. The authors report two cases of peri-renal hematoma on anticoagulant therapy involving a pathological kidney, giving serious complications and requiring surgery for nephrectomy. PMID- 2313108 TI - [Carcinoma in situ of the testis (CIST). Apropos of 7 cases]. AB - Can cancer of the testis be detected at a pre-invasive in situ stage? What are the situations where there is a high suspicion of this stage and of what value is early detection and by what diagnostic and therapeutic means can this histological entity, described by Skakkebaek in 1972, be controlled? Taking into account the study of 7 patients who presented with a CIST, this article tries to define the response of the authors to these questions. PMID- 2313111 TI - [Signet ring cell carcinoma of the bladder. Apropos of a case]. AB - Signet ring cell adenocarcinoma of the bladder is a very rare tumor. It presents similar to the linitis plastica type of gastric adenocarcinoma. The authors report a new case and analyze the medical literature in order to specify the diagnostic problems and the histogenesis of this tumor. PMID- 2313110 TI - [leiomyoma of the bladder. Apropos of a case]. AB - Leiomyomas are the most common form of benign mesenchymal bladder tumour. While the diagnosis may be suggested on radiological investigations, it can only be confirmed by histology. The prognosis is good, the treatment being exclusively surgical. PMID- 2313112 TI - [Emphysematous pyelonephritis]. AB - The authors report on a case of a emphysematous pyelonephritis due to Klebsiella pneumoniae, occurring in a diabetic patient and successfully treated by nephrectomy. They compare it to the literature. PMID- 2313113 TI - [Importance of unrecognized bladder lesions in the long-term results of antireflux reimplantation in "primary" supposed vesico-ureteral reflux]. AB - Based on two cases of antireflux uretero-vesical reimplantation for so-called primary reflux and a normal lower urinary tract, the author demonstrates the possible occurrence of major secondary bladder lesions. These lesions seriously compromise the results of reimplantation, sometimes even after an initial success (case 1). The etiology of these bladder lesions remains poorly defined: occult neurological lesions? iatrogenic lesions? Their treatment is difficult and their prognosis is poor. PMID- 2313114 TI - Complement activation by pulsed tunable dye laser in normal skin and hemangioma. AB - Pulsed tunable dye laser (577 nm) (PTDL) therapy induces hemoglobin coagulation and tissue necrosis, which is mainly limited to blood vessels. To define whether this treatment activates complement in normal skin and senile hemangioma, we analyzed complement deposition in blood vessels by immunofluorescence. C3 fragments, C8, and C9 were detected with specific polyclonal antibodies. The membrane attack complex of complement (MAC) was demonstrated with a monoclonal antibody which reacts only with a neoantigen of MAC. Amplification of C3 deposition by the alternative pathway was determined on cryostat sections by indirect immunofluorescence with use of C4 deficient guinea pig (GP) serum. Normal skin and hemangiomas from three individuals were studied. In PTLD irradiated normal skin, the main findings were as follows: 1) C3 fragments, C8, C9, and MAC were deposited in vessel walls; 2) these deposits were not due to denaturation of the proteins since they became apparent only 7 min after irradiation, contrary to immediate deposition of transferrin at the sites of erythrocyte coagulates; 3) the C3 deposits were shown to amplify complement activation by the alternative pathway, a reaction which was specific since tissue necrosis itself did not lead to such amplification; 4) these reactions preceded the local accumulation of polymorphonuclear leucocytes. Tissue necrosis was more pronounced in the hemangiomas. The larger angiomatous vessels in the center of the necrosis did not fix complement significantly. By contrast, complement deposition in the vessels situated at the periphery was similar to that observed in normal skin with one exception: C8, C9, and MAC were detected in some blood vessels immediately after laser treatment, a finding consistent with assembly of the MAC occurring directly without the formation of a C5 convertase. These results indicate that complement is activated in PTDL-induced vascular necrosis, and might be responsible for the ensuing inflammatory response. PMID- 2313115 TI - Cimetidine-induced augmentation of allergic contact hypersensitivity reactions in mice. AB - BALB/c mice were treated with cimetidine (100 mg/kg) or saline, intraperitoneally, twice daily, from days 0-2 or days 7-9 after sensitization with 0.1%, 2,4,6-trinitro-1-chlorobenzene (TNCB) on day 0. On day 7, the mice were challenged with 1% TNCB to one ear. Ear swelling responses (as an index of sensitization), serum histamine levels, and biopsy specimens of challenged ears were evaluated in groups of cimetidine- or saline-treated mice at 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after challenge. Additional controls included mice injected with saline or cimetidine and challenged with, but not sensitized to, TNCB (irritant controls). Treatment with cimetidine during the induction but not the elicitation of allergic contact hypersensitivity (ACH) produced a significant enhancement of the response throughout the first 48 h. There was no effect of cimetidine on antigen-presenting cells within the epidermis which might account for this enhancement. Similarly, no difference in mast cell morphology or serum histamine levels between cimetidine- and saline-treated groups was observed. Histologically, the cimetidine-treated animals showed a more intense cellular infiltrate, which was most noticeable at 24 to 48 h, at which time numerous subcorneal and perifollicular neutrophilic abscesses were observed. To further investigate the mechanism of action of cimetidine, mice were injected with cyclophosphamide (150 mg/kg) 2 d prior to sensitization. Mice treated with cyclophosphamide alone or in combination with cimetidine showed no additive or synergistic effect upon the ear swelling response. We conclude that enhancement of ACH by cimetidine is independent of any effect on mast cells or antigen presenting cells, but may relate to a cimetidine-induced inhibition of the induction of T-suppressor cells at the time of sensitization. PMID- 2313116 TI - High-affinity binding and lack of growth-promoting activity of 12(S) hydroxyeicosatetraenoic acid (12(S)-HETE) in a human epidermal cell line. AB - The arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) is assumed to play an important role in skin physiology and pathophysiology. Specifically, it has recently been discussed as a growth promoting agent in keratinocytes. Our aim was to find out whether epidermal cells possess specific receptors for 12-HETE which would mediate the effects of this eicosanoid in skin, including the putative growth stimulating activity. We could identify specific binding sites for 12(S)-HETE on the human epidermal cell line SCL-II. The analysis of binding data revealed a single class of binding sites with a Kd of 2,6 nM and a Bmax of 216,000 sites per cell. The binding was saturable, readily reversible, and specific for 12(S)-HETE with lower affinities for other monoHETE. We failed to detect any significant proliferative activity of 12(S)-HETE in the same epidermal cell line, although we applied three independent methods for evaluation of cell growth and used a concentration of 12(S)-HETE which should enable an optimal receptor occupancy. Thus, epidermal cells possess high-affinity 12(S)-HETE binding sites which are likely to be involved in the effects of this eicosanoid in epidermis. However, biologic effects other than direct growth stimulation seem to be transduced by 12(S)-HETE receptors in epidermal cells which need further investigation. PMID- 2313117 TI - BE-2 antigen: appearance in activation and long-term growth of T cells. AB - The BE-2 lymphocyte surface protein is frequently expressed by the malignant cells of cutaneous T-cell lymphoma (CTCL) but is not detectable on the surface of normal resting peripheral blood lymphocytes. The expression of BE-2 by normal T cells can be induced by lectin stimulation. Membrane expression of BE-2 surpasses that of the membrane receptor for IL-2, another T-cell activation marker, at day 5. The peak expression of BE-2 appears at day 6-8. The appearance of BE-2 could also be demonstrated after anti-CD3 and allogeneic stimulation. Long-term T-cell clones derived from normal donors and maintained in culture with periodic stimulation were also found to express BE-2 continuously. Thus, BE-2 is a late activation marker not expressed on normal peripheral blood lymphocytes and pathologically expressed on circulating malignant cells in the disease CTCL. PMID- 2313118 TI - Segmental cell kinetics of the human anagen hair: a DNA-flow cytometric analysis. AB - The cell kinetics of anagen scalp hair taken by punch biopsies from 70 healthy male volunteers were determined at nine different defined bulbar and follicular hair segments using microdissection and DNA-flow cytometry. The highest mean proliferative activity (S-phase) was measured within the lowermost bulbar segment (14.0%), but decreased to 7.6% at Auber's segment and to 5.9% at the follicle isthmus. Notably, the S-phase data of the upper follicular segments (subdermal 2.4%, infundibular 2.4%) were found to be similar to those of the epidermis (2.5%). This study supporting and supplementing former autoradiographic investigations on human hair matrix epithelium clearly demonstrates the main proliferative activity of the anagen hair follicle being localized in the bulbar segments below Auber's level. Moreover, the method described is well suited for studying the effects of agents influencing cell growth (e.g., hormones or drugs) on the cell kinetics of different anagen hair compartments. PMID- 2313119 TI - Ultrastructural localization of lectin-binding sites in normal skin. AB - The distribution of carbohydrate residues in keratinocytes of normal epidermis was studied. Normal skin was embedded in Lowicryl. Thin sections were incubated with concanavalin A (Con A), peanut agglutinin (PNA), wheat germ agglutinin (WGA), Ulex europaeus agglutinin I (UEA I), dolichos biflorus agglutinin (DBA), and soybean agglutinin (SBA). A positive reaction in the dermis, in the basal lamina (lamina densa, lamina lucida), intracellularly and within the plasma membrane including the desmosomes was obtained after incubation with Con A and WGA. PNA binding sites were found predominantly in the plasma membrane between the desmosomes. The labeling with Con A, WGA, and PNA was most pronounced in the upper stratum spinosum and granulosum. Incubation with UEA revealed heavy labeling of the keratohyalin granules and the cytoplasm of the corneocytes. Incubation with DBA and SBA revealed weak labeling of the keratinocytes. The study of the distribution of carbohydrate residues in normal epidermis is important, since alterations in this distribution might be linked to autoimmunity or malignant transformation. PMID- 2313121 TI - Heterosexual transmission of hepatitis B virus in Belle Glade, Florida. Belle Glade Study Group. AB - A population-based serosurvey of human immunodeficiency virus in Belle Glade, FL, enabled evaluation of risk factors for hepatitis B virus (HBV) infection in this racially mixed community. Serum samples from 725 adults and 130 children were tested for markers of HBV infection, and histories of exposure to HBV were obtained by interview. The overall prevalence of past or present HBV infection was 26%; prevalence was 9% among whites, 5% among Hispanics, 30% among blacks, and 57% among Haitians. Prevalence of HBV infection was 3% in children aged 2-10 years and increased to 31% in adults greater than 17 years. Of adults seropositive for HBV, only 5% had homosexual partners or used parenteral drugs, but 47% had a positive serologic test for syphilis. Factors associated with HBV infection in adults were positive serologic test for syphilis (odd ratio [OR] = 3.1; 95% confidence limits [CL] = 2.0, 4.8), and having had two or more lifetime heterosexual partners (OR = 3.2; 95% CL = 1.6, 6.4). In this community, HBV infection was transmitted predominantly by heterosexual contact. PMID- 2313120 TI - Inflammatory properties of human C5a and C5a des Arg in mast cell-depleted human skin. PMID- 2313122 TI - In vitro immune responses to hepatitis B surface antigens S and preS2 during acute infection by hepatitis B virus in humans. AB - This study evaluated the in vitro immune responses to different components of the hepatitis B surface antigen (HBsAg) over the course of acute hepatitis B virus (HBV) infection. Early in the convalescent phase of infection, while HBsAg was present in the serum, peripheral blood mononuclear cells (PBMCs) were stimulated with preS2 peptide or hepatitis B surface protein. Specific IgG directed to different components of HBsAg was produced without a polyclonal increase in total IgG production. Stimulation with preS2 peptide produced IgG to the preS2 peptide (anti-preS2) and to the S antigen (anti-HBs). Hepatitis B surface protein stimulation produced anti-HBs but not anti-preS2. After this initial reactive phase, the PBMCs did not produce specific antibody when stimulated with either component of HBsAg; this effect lasted greater than 1 year. At some time 1-2 years after acute infection, the pattern of in vitro S antigen- and preS2 antigen stimulated anti-HBs response reemerged in the PBMCs. Reemergence of sustained preS2 peptide-stimulated anti-preS2 response was not observed. PMID- 2313124 TI - Detection of human immunodeficiency virus DNA using the polymerase chain reaction in a well-characterized group of homosexual and bisexual men. AB - The polymerase chain reaction (PCR) for human immunodeficiency virus type 1 (HIV 1) DNA was performed on specimens from 197 homosexual and bisexual men enrolled in studies of HIV-1 infection. Thirty cycles of amplification were conducted, followed by detection with probes corresponding to two gag primer pairs (SK 38/39 and SK 101/145). Of 107 men who were HIV-1 antibody-negative, 105 (98%) were PCR negative. Two who were initially PCR-positive antibody-negative were PCR- and antibody-negative on repeat testing of both the same specimen and specimens drawn 8-10 months later; this suggests that the first PCR results were false-positive. Of 90 men who were antibody-positive, PCR was positive in 87 (97%), including all 13 with AIDS, all 22 with AIDS-related conditions, all 11 with generalized lymphadenopathy only, and 41 (93%) of 44 without signs or symptoms of HIV-1 infection. On repeat testing, all 3 PCR-negative, antibody-positive men were PCR positive. In this population and with this technique, PCR had excellent agreement with the HIV-1 antibody test. PMID- 2313123 TI - Antibody to p40tax protein of human T cell leukemia virus 1 and infectivity. AB - To investigate the physiologic significance of antibody to human T cell leukemia virus type 1 (HTLV-1) tax gene product (p40tax), 147 male and 243 female HTLV-1 carriers were examined for anti-p40tax, and 104 carriers were checked for anti p40tax an average of 5.4 times during an 8-year period. Prevalence of anti-p40tax was significantly higher in female (62.6%) than in male subjects (51.0%; P less than .05). Anti-p40tax status did not change in most during the observation period. There were significantly more HTLV-1 carriers among children of anti p40tax-positive mothers (45.3%) than among those from anti-p40tax-negative mothers (20.0%; P less than .01). However, no significant difference was observed between wives of p40tax-positive and -negative men. The p40tax antibody may be a marker of relative infectivity of HTLV-1, albeit an imperfect one. PMID- 2313125 TI - Pancreatic lesions and hypoglycemia-hyperinsulinemia in scrapie-injected hamsters. AB - Hamsters injected intracerebrally with scrapie strains 139H or 22CH or with normal hamster brain were assessed for body weight periodically throughout the incubation period. Animals injected with the scrapie strains became obese before the appearance of the motor changes that are indicative of the start of clinical disease. During the latter part of the incubation period and during clinical disease, animals were hypoglycemic and showed marked hyperinsulinemia. At autopsy, there was marked hyperplasia and hypertrophy of the cells of the islets of Langerhans. Thyroid, adrenal glands, liver, and kidney also were enlarged. The data suggest a severe endocrinopathy and point to new areas of pathologic and clinical changes that can be assigned to unconventional slow infections. PMID- 2313126 TI - Widespread silent transmission of pertussis in families: antibody correlates of infection and symptomatology. AB - Four children with pertussis and their 18 family members were subjects of a 1 year study to detect infection and antibody responses to Bordetella pertussis. Attack rate for pertussis infection in contacts was 83%. Two-thirds of cases in these immunized contacts were subclinical. All infected family contacts had diagnostically elevated serologic tests for pertussis at the time the index case was diagnosed. Culture identified only 20% of infected contacts. Infected individuals had a mean of 5.5 of 10 antibody tests diagnostic for recent infection. ELISA assay for IgG to pertussis toxin and assay for IgA to filamentous hemagglutinin on serum and nasal secretions were the most discriminating diagnostic tests. Index cases and immunized contacts had different type and timing of antibody responses, making a single assay or sampling unable to identify all infected individuals. Symptomatic infection was characterized by higher magnitude of pertussis toxin antibody response and asymptomatic infection by filamentous hemagglutinin. After pertussis immunization, immunity to disease is greater than is protection from infection. PMID- 2313127 TI - Natural history of pertussis antibody in the infant and effect on vaccine response. AB - To better characterize the transplacental transfer and persistence of pertussis antibodies and their role in the immune response to vaccine, concentrations of pertussis agglutinins and antibodies to lymphocytosis promoting factor (LPF) and filamentous hemagglutinin (FHA) were measured in three distinct groups of serum. Transplacental pertussis IgG antibody concentrations in newborns were found to be comparable to corresponding maternal concentrations and to decline with a half life of approximately 6 weeks. By the age of 4 months, most infants had no detectable antibodies to LPF or FHA. Higher concentrations of maternally derived antibody to LPF were associated with a significantly weaker antibody response to conventional vaccine. In contrast, acellular vaccine stimulated superior antibody production, regardless of antecedent concentrations of antibody to LPF. The data support continuation of the current schedule of pertussis immunization and further efforts to develop an acellular vaccine for use in young infants. PMID- 2313128 TI - Death in shigellosis: incidence and risk factors in hospitalized patients. AB - The total number of admissions and deaths of patients with shigellosis were ascertained at the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, 1974-1988, and the characteristics of 67 patients who died were compared with those of 134 discharged alive. Of 9780 Shigella-infected inpatients, 889 (9.1%) died; 32.3% of deaths occurred in children less than 1 year of age. Fatality rates were highest (10.3%) in Shigella sonnei-infected patients and lowest (6.7%) in Shigella dysenteriae type 1 infected patients. Age less than 1 year, lack of breast feeding in patients 1-2 years of age, hypothermia, severe malnutrition, severe dehydration, altered consciousness, abdominal distension, thrombocytopenia, hypoproteinemia, hyponatremia, hypoglycemia, renal failure, and bacteremia were all significantly more common in case patients. In a multivariate analysis, younger age, decreased serum protein, altered consciousness, and thrombocytopenia were predictive of death. Thus in Bangladesh the fatality rate for hospitalized patients infected with any species of Shigella remains high despite relatively intensive inpatient care, and young, hypoproteinemic patients are at greatest risk of fatal illness. PMID- 2313129 TI - Patient-to-patient transmission of Campylobacter pylori infection by fiberoptic gastroduodenoscopy and biopsy. AB - Three instances of subclinical reinfection with Campylobacter pylori were observed in two successfully treated patients during follow-up of C. pylori gastritis. The reinfections occurred 1 month and 21 months (patient 1) and 32 months (patient 2) after the completion of antibacterial treatment. Sequential measurement by ELISA of serum IgG antibody levels to the microorganism showed a significant increase in two of the three instances of reinfection. Patient-to patient transmission was proved by restriction enzyme analysis of bacterial DNA. Between patients the endoscope had been mechanically cleaned using a detergent and treated with 70% ethanol. The risk of gastroscopic cross-infection with C. pylori was estimated by retrospective analysis of the data of 281 negative examinations (107 in 47 initially negative patients and 174 in 37 cured patients). The frequency in uninfected patients of documented endoscopic transmission of C. pylori infection was 1.1% in this study, corresponding with three iatrogenic acquisitions of manifest infection for every 1000 gastroduodenoscopies in our clinic. PMID- 2313130 TI - Endogenous and exogenous reinfections by Haemophilus influenzae in patients with chronic obstructive pulmonary disease: the effect of antibiotic treatment on persistence. AB - To analyze whether exacerbations in chronic obstructive pulmonary disease (COPD) coincide with reinfection by Haemophilus influenzae, 16 COPD patients were studied longitudinally for 3 years. Exacerbations coincided with reinfection by H. influenzae, either endogenous, by a strain with a DNA fingerprint indistinguishable from the strain previously present but with another major outer membrane protein (MOMP) pattern (2 patients), or exogenous, by a strain with a different DNA fingerprint and MOMP pattern (3 patients). The other patients, remaining in an infectious state without clear exacerbations for longer periods, were persistently infected by a particular H. influenzae strain (median persistence time, 5.5 months; range, 2-23 months). Of 8 antibiotic-treated patients, 7 remained infected by H. influenzae with the same DNA fingerprint, although all strains were sensitive to the antibiotics prescribed. Results of the study suggested that exacerbations in COPD patients coincide with endogenous or exogenous reinfection by H. influenzae, persistently infected patients keep the same H. influenzae strain for longer periods, and antibiotic treatment was not effective in eradicating H. influenzae. PMID- 2313131 TI - Maternal gonococcal infection as a preventable risk factor for low birth weight. AB - With the objective of determining if specific sexually transmitted diseases (STDs) are associated with prematurity (birth weight less than or equal to 2500 g and gestational age less than or equal to 36 weeks), a case-control study was conducted to evaluate women for serologic evidence of syphilis and human immunodeficiency virus infection and microbiologic evidence of cervical infection with Neisseria gonorrhoeae, Chlamydia trachomatis, and Haemophilus species and vaginal infection with genital mycoplasma, Streptococcus agalactiae, and Enterobacteriaceae. Gram stains of vaginal secretions were evaluated for bacterial vaginosis. Among 166 cases and 175 controls, infection with N. gonorrhoeae was associated with preterm birth. Four percent of controls and 11% of cases were infected with N. gonorrhoeae (odds ratio 2.9, 95% confidence interval 1.2-7.2). This association was independent of age, rupture of membranes, and hypertension. Other STDs were not associated with preterm birth. The attributable risk of gonococcal infection was 14%. Gonococcal infection appears to be responsible for a substantial proportion of premature births and is theoretically preventable by antenatal case detection and treatment. PMID- 2313133 TI - Pharmacokinetics, tissue distribution, and toxicity of free and liposomal amphotericin B in diabetic rats. AB - The pharmacokinetics, tissue distribution, and toxicity of free amphotericin B (free AmB) or amphotericin B encapsulated in liposomes (L-AmB) were characterized in experimental diabetic rats and compared with data obtained from nondiabetic rats. After 7 days of insulin-controlled diabetes or saline, each rat was administered a single intravenous bolus dose of free AmB or L-AmB (0.8 mg/kg body weight). Blood samples were obtained before administration and serially thereafter for the assessment of serum pharmacokinetics, nephrotoxicity, and biochemical parameters. Before drug treatment, diabetic rats demonstrated marked increases in serum cholesterol and triglyceride levels compared with levels in nondiabetic rats. A significant increase in serum creatinine levels was observed in nondiabetic rats given free AmB but not in other groups. Whereas AmB pharmacokinetics were significantly altered in diabetic rats administered free AmB, no kinetic differences were found between groups given L-AmB. Renal AmB levels were markedly increased in nondiabetic rats given free AmB compared with those in all other groups. Furthermore, significantly greater concentrations of free AmB were found in lung tissue of rats administered L-AmB independent of disease state. Hepatic levels of AmB were reduced in diabetic rats administered free AmB. The disposition and nephrotoxicity of L-AmB were independent of vascular lipid composition. PMID- 2313132 TI - Successful treatment of malignant external otitis with oral ciprofloxacin: report of experience with 23 patients. AB - Twenty-three consecutive patients with malignant external otitis (MEO) were treated with oral ciprofloxacin, 1.5-2.25 g/day for 6 weeks. Treatment was combined with local surgical debridement. Patients were discharged early for ambulatory follow-up. Few minor side effects were reported, and full compliance with the study drug was observed. In 21 patients cure was achieved; in 2 the response was not adequate. Oral ciprofloxacin is an effective, convenient, nontoxic, economically justified alternative to the combination intravenous therapy previously advocated. PMID- 2313134 TI - Detection by immune electron microscopy of 27-nm viral particles associated with community-acquired diarrhea in children. AB - The proportion of diarrheal illnesses of unknown origin that were associated with small round virus (SRV, 23-38 nm) particles among children less than 2 years old attending an outpatient clinic in Baltimore was determined. During a 9-month period, stool specimens from 188 patients with acute diarrhea and 108 healthy age matched control children were examined for enteric bacterial pathogens, protozoa, enteric adenovirus, and rotavirus. An enteropathogen was identified in 75 patients (40%) and in 21 controls (20%). A random sample of specimens without an identifiable pathogen was then examined for SRV particles by immune electron microscopy (IEM) using commercial human gamma globulin. Viruses of 26-30 nm diameter that were not enteroviruses were detected in specimens from 9 (12.5%) of the 72 patients and 1 (1.8%) of the 53 control subjects (P less than .04). Of 6 patients with available acute and convalescent sera, 4 demonstrated a significant immune response when tested by IEM. All patients experienced a mild, self-limited (1-3 days) illness. These findings suggest that SRV may be endemic in the Baltimore community and may result in clinically significant diarrheal illnesses. PMID- 2313135 TI - Pathogenesis in Bordetella species. PMID- 2313136 TI - Genital ulcers and male circumcision as risk factors for acquiring HIV-1 in Zambia. PMID- 2313137 TI - Amphotericin B-induced malignant hypertensive episodes. PMID- 2313138 TI - Bronchiolitis obliterans possibly associated with amphotericin B. PMID- 2313139 TI - Hematogenous osteitis due to Yersinia enterocolitica. PMID- 2313140 TI - Stimulation of myeloid colony growth from peripheral blood by medium with an initially low osmolality. AB - The clonal growth of myeloid colonies from peripheral blood was maximal when cultures were established with an initial osmolality of 220 mosmol/kg which increased during incubation as a result of partial drying. When osmolality was stabilized by secondary humidification, the optimum osmolality was 270 mosmol/kg, but growth was always two- to fivefold less than similar cultures established at low osmolality and incubated on an open shelf. Cultures established at 270 mosmol/kg or above were statistically similar whether or not drying was eliminated. Maximum colonies were apparent after 14 days incubation under both conditions; addition of conditioned medium did not alter the pattern of growth. The greater sensitivity of cultures established at 220 mosmol/kg is advantageous when assaying circulating progenitors in pathological conditions where a low number of granulocyte/macrophage colony-forming units is common. PMID- 2313141 TI - Recombinant human erythropoietin corrects anemia of blood loss: a study in the dog. AB - In order to evaluate the possibility of using recombinant human erythropoietin (rhEpo) for the prevention and correction of anemia due to blood loss and as an adjuvant for autologous blood transfusion, its preventive and therapeutic effects were evaluated in beagles in which anemia was induced by repeated phlebotomies. Two hundred U/kg of rhEpo were administered i.v. four or nine times every two weeks for six weeks. Phlebotomies (25 ml/kg of body weight) were conducted three times at two-week intervals. rhEpo was found to successfully prevent and correct anemia caused by the phlebotomies. Concurrent administration of iron increased efficacy. The findings obtained in the present study suggest that rhEpo is useful both for the treatment of anemia caused by blood loss due to surgery and as an adjuvant therapy for pre-deposit autologous blood transfusion. PMID- 2313143 TI - [A continuous-step density percoll gradient for use in AIH and life table analysis of pregnancy rates]. AB - For use in artificial insemination with husband's semen (AIH), a continuous-step Percoll density gradient technique was used to wash and concentrate sperm from ejaculate. To evaluate usefulness, the pregnancy rates were analyzed by the life table method. 1. After washing by the continuous-step Percoll density gradient method, sperm density increased from 28.8 X 10(6)/ml (original semen) to 40.9 X 10(6)/ml and sperm motility improved from 52.4% (original semen) to 77.0% respectively. 2. A group of 119 infertile patients whose diagnosis involved oligoasthenozoospermia, cervical factor and unexplained infertility were selected for AIH. After 640 insemination cycles, 37 women conceived with a pregnancy rate of 31.1%. By using life table analysis, the cumulative conception probability rate reached 0.652 after 13 insemination cycles. 3. Cumulative pregnancy rates by diagnostic category were 0.494 in male factor and 0.745 in cervical factor after 12 cycles, respectively. 4. The poorest results were obtained in unexplained infertility with a cumulative pregnancy rate of only 0.355 after 12 cycles. 5. In the follow up study, 24 viable babies were born and seven (18.9%) resulted in spontaneous abortion in the first trimester. These results indicate that the continuous-step Percoll density gradient technique is useful for improving the pregnancy rate in AIH. PMID- 2313142 TI - [Therapeutic values of prostaglandin D2 in nude mice bearing human ovarian carcinoma]. AB - In vitro and in vivo effects of prostaglandin D2 on human ovarian cancer growth were examined by using a cell line, designated HR, derived from ascites of patient with serous cystadenocarcinoma of the ovary. The HR cell proliferation in vitro was dose-dependently inhibited at prostaglandin D2 concentrations between 0.1 and 4.0 micrograms per ml. The results of a 51Cr-release assay seemed to indicate that the inhibition resulted from a direct cytotoxic effect exerted by prostaglandin D2. All DNA, RNA, and protein synthesis by the HR cells was also inhibited in a dose-dependent manner with 48 hr exposure to prostaglandin D2. When nude mice were inoculated with 5 X 10(5) HR cells, the 50% survival time in the untreated group was 52 days. The 50% survival time of nude mice treated with 12 mg (but not 4 mg) of prostaglandin D2 per kg was significantly prolonged to 67 days, in addition to a significant inhibition of the tumor growth. Adjuvant effects of prostaglandin D2 on cisplatin in relation to tumor growth were also studied. Combinations of 0.2 or 0.4 microgram cisplatin per ml and 0.05 or 0.1 microgram prostaglandin D2 per ml, which did not affect the HR cell proliferation alone, resulted in a significant inhibition of cell proliferation. In addition, the tumor take of HR cells by nude mice in groups treated with a combination of cisplatin and prostaglandin D2 was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313145 TI - [Usefulness of magnetic resonance imaging (MRI) in pre-treatment evaluation of the extension of uterine cervical carcinoma]. AB - Fifty-four patients with primary carcinoma of the cervix were examined by magnetic resonance imaging (MRI). Different pulse sequences with T1 and T2 weighting were employed to determine optimum tissue contrast. The tumor had a uniform signal intensity similar to the myometrium on the T1 weighted image. In contrast, the tumor signal intensity increased on the T2 weighted image. In our series the primary tumor was clearly defined in nine of twenty patients with stage 0 and I disease and thirty-three of thirty-four patients with stage II, III and IV disease. In addition, the primary tumor was clearly defined in four patients who had unsatisfactory colposcopic findings (UCF). Parametrial invasion of the tumor was well depicted on transverse planes in four of twelve sides with stage IIb disease and twenty-eight of thirty-four sides with stage III and IV disease. T1 weighted images provided excellent tissue contrast between the high signal from pelvic fat and the low intensity of tumor tissue enabling demonstration of involvement of the pelvic side wall. Vaginal invasion was also clearly seen on T2 weighted sagittal images in seventeen of twenty-six patients. In conclusion, MRI is not only useful but is also a non-invasive method of detecting primary tumor and extra-uterine extension of cervical carcinoma. PMID- 2313144 TI - [Clinical significance of CA19-9 for endometriosis]. AB - We investigated the usefulness of measuring the serum CA19-9 concentration in the diagnosis and therapeutic monitoring of endometriosis, and compared it with the serum CA125 concentration. We added an immunohistochemical study on CA19-9 and CA125 to find their localization in the various lesions of endometriosis. 1. The positive rate of serum CA19-9 in patients with endometriosis is 52.0% and that of CA125 is 48.0%. When both markers are examined, their positive rate increases to 71.4%. 2. As the Beecham classification stage advanced, the serum CA19-9 positive rate tended to increase. 3. The patients with endometriosis were followed up after surgery or during Danazol therapy. CA19-9 correlated closely with the clinical course. 4. The immunohistochemistry of CA19-9 shows that it localizes in chocolate cysts, but not in the lesions of adenomyosis. CA125 is seen in both lesions. The localizing of CA19-9 is thus seen to be different from that of CA125. It is concluded that the measurement of the serum CA19-9 concentration combined with that of CA125 is useful in the diagnosis and therapeutic monitoring of endometriosis. PMID- 2313146 TI - [Bone mineral loss due to premenopausal oophorectomy assessed by dual photon absorptiometry]. AB - Although it has been reported that bone mineral loss due to oophorectomy (OPX) occurs mainly in the axial bone, especially in the trabecular bone, there have been no reports on the use of this method for simultaneous total body calcium measurement. Furthermore, the occurrence of bone mineral loss in regional bone mineral density (BMD) after OPX has not been clarified. We investigated whether there is a decrease in regional BMD after OPX, and whether there are regional differences in bone mineral loss following OPX. The BMD was measured by dual photon absorptiometry in 21 premenopausal oophorectomized subjects (mean age: 46.8 +/- 4.0 yr, mean duration after OPX: 48.0 +/- 40.0 months) and 19 age- and body size-matched females. In OPX subjects, the spinal BMD was significantly lower (corresponding to 87.0 +/- 2.4% of control) than those of the cranium, arms and legs (92.1 +/- 2.6, 97.2 +/- 1.2, 95.4 +/- 1.6% respectively). Furthermore the oophorectomized subjects were divided into three groups according to duration after OPX as follows; within 1 (n = 7), 2-5 (n = 7) and over 6 years (n = 7). The spinal BMD had already tended to decrease in the within 1 year group and significantly decreased in the over-6-year group. On the other hand, there were no differences in the within 1 year group in arm and leg BMD compared with the control. However, in the over-6-year group they were significantly decreased. These results suggest that bone mineral loss in oophorectomized subjects occurs mainly in spinal bone, and the degree of bone mineral loss might be different in regional bone. PMID- 2313147 TI - [A case of amniotic band syndrome--in view of the pathogenesis]. PMID- 2313149 TI - [A protocol of in vitro fertilization and embryo transfer for a high pregnancy rate]. PMID- 2313148 TI - [A recurrent case of liposarcoma arising from the left uterosacral ligament with histological findings of malignant mesenchymoma]. PMID- 2313151 TI - [87th symposium of the Japanese Society of Internal Medicine. Tokyo, 5-7 April 1990. Abstracts]. PMID- 2313150 TI - [Bilateral ovarian pregnancy: a case report]. PMID- 2313152 TI - Conservative treatment of low rectovaginal fistula in Crohn's disease. AB - A conservative operative treatment of anovaginal fistula in Crohn's disease is described. This consists of simply laying open the fistula with section of the rectovaginal septum and the portion of external sphincter superficial to the fistula. The operation may be performed in the presence of rectal involvement even during an acute exacerbation of the disease; a temporary defunctioning stoma is not required. The fistula was of the high transsphincteric type in three patients and low transsphincteric in six. All wounds healed in less than 3 months without any further surgery. At a mean follow-up of 29 months, 6 had perfect continence and 3 could control solid but not liquid stools nor flatus. PMID- 2313153 TI - The investigation of anorectal dysfunction in the solitary rectal ulcer syndrome. AB - To investigate anorectal function in solitary rectal ulcer syndrome 22 patients were studied by means of balloon expulsion, intestinal transit time, barium enema and evacuation proctography. Half of the patients tested had difficulty in expelling a water filled balloon. Delay in intestinal transit was noted in only three patients. Barium enema was of little benefit in diagnosing the condition. Evacuation proctography was the investigation of choice in that it showed at least one abnormality of pelvic floor function in all of the patients and can help select patients for surgery. PMID- 2313154 TI - The role of transient internal sphincter relaxation in faecal incontinence? AB - Twenty-five (18%) of 140 incontinent patients and 6 (17%) of 35 normal controls showed episodes of spontaneous internal sphincter relaxation during 30 min multiport manometric and electromyographic recording under resting conditions. The episodes lasted at least 15 s and reduced the pressure in the outermost anal channels by at least 20 cm of water. Patients exhibited more episodes of relaxation than controls (4.3 +/- 0.6 vs 2.3 +/- 0.2 per subject; mean +/- SEM; p less than 0.05) and the pressures fell to lower values (19 +/- 1 vs 42 +/- 5 cm water, p less than 0.01), but the duration of relaxation was not significantly different (53 +/- 4 vs 40 +/- 7 s). Episodes of spontaneous relaxation were associated with simultaneous rectal contractions in 33% of the normal subjects and 45% of incontinent patients. Unlike normal subjects, most of the episodes of transient relaxation recorded in the incontinent group were not associated with compensatory increases in the electrical activity of the external anal sphincter (77% vs 17%; p less than 0.05). Over 50% of the incontinent patients who showed spontaneous relaxation also showed post squeeze or post-strain IAS relaxations whereas these were seen in less than 6% of the normal subjects with spontaneous relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313155 TI - Rectal compliance: a critical reappraisal. AB - Compliance is a widely measured parameter of rectal function. Its value is determined clinically by recording pressure changes associated with volume infusion into a rectal balloon. This paper examines the inherent assumptions of the rectal balloon technique and discusses several of its shortcomings. A stricter definition of rectal compliance is needed, and in vivo compliance should be correlated with the directly measured mechanical properties of the rectal wall. PMID- 2313156 TI - A retrospective study of colostomies, leaks and strictures after colorectal anastomosis. AB - A review was undertaken of 360 patients undergoing elective left-sided colonic or rectal resections with primary anastomosis, under the care of one surgeon, over a nineteen year period. The incidence, aetiology and management of anastomotic leaks and strictures was studied and the role of proximal diverting colostomy considered. Perioperative mortality was 2.7%. The incidence of anastomotic leaks was 24.4%. Leaks were more common when anastomoses were low, were sutured or were constructed by trainees. Strictures developed in 5.8%. Local recurrence of tumour was the cause of 25% of these strictures. Anastomotic leakage was the principal cause of benign strictures; those developing in association with leaks were more likely to require surgical intervention. There was no evidence that delay in colostomy closure contributed to the development of benign anastomotic strictures. It was not possible to determine whether the presence of a colostomy affected the incidence of leaks but the local effects of such leaks were mitigated in patients with colostomies. Where a minor leak had occurred it was not necessary to wait for complete anastomotic healing before closing the colostomy. After major leaks, colostomy closure before complete healing was associated with further anastomotic problems in 16.0% of cases. PMID- 2313158 TI - Perineal colostomy and electrostimulated gracilis "neosphincter" after abdomino perineal resection of the colon and anorectum: a surgical experience and follow up study in 47 cases. AB - A series of 47 patients undergoing abdomino-perineal resection of the distal colon and anorectum and construction of a continent perineal colostomy using electrostimulated gracilis muscle is described. External and implanted pulse generators have both been used. An analysis of complications and oncological data are reported. There was no operative mortality. The incidence of complications, divided into three classes, mild (62%), moderate (27%) and severe (11%), has not significantly altered the functional results, with the exception of early ischaemia of the colonic stump in two cases. During the first 22 cases, no preoperative oncological staging was performed. In the last 23 patients endorectal ultrasonography and CT scanning were carried out. Functional results were evaluated by electromanometry, electromyostimulation and dynamic defaecography. Clinical data assessed postoperatively showed good function in 65% of cases, fair in 22.5% and poor in 12.5%. The quality of life in 15 patients with a perineal colostomy and electrostimulated gracilis was significantly better than in 15 patients having an abdomino-perineal resection without gracilis plastic reconstruction. PMID- 2313157 TI - Gynaecological problems related to anatomical changes after conventional proctocolectomy and ileostomy. AB - Seventy-one women who had a proctocolectomy for ulcerative colitis (n = 41) or Crohn's disease (n = 30) were interviewed in the follow-up clinic about gynaecological problems and fertility. All women were examined by an independent gynaecologist and abnormalities of the internal genital tract were registered. Forty-nine per cent (35/71) of the women had a distressing vaginal discharge after proctocolectomy, compared with 9% (6/71) before surgery. At the gynaecological examination 45% (32/71) had a heavy vaginal secretion with- out any signs of an acute vaginal infection. In 68% (30/44) fluid retention in the vagina was associated with a caudally firmly fixed and dilated posterior vaginal fornix. Twelve per cent (8/66) of the women reported dyspareunia before surgery. After surgery, 27% (18/66) complained of this symptom. Fertility was significantly reduced after surgery since only 37% (10/27) of the women who attempted to become pregnant succeeded within 5 years follow-up. The corresponding figure before surgery was 72% (39/54). Those who conceived went through pregnancy and parturition without any incident, 6 of 21 delivered by caesarean incision. In conclusion, conventional proctocolectomy in women will result in distressing vaginal discharge, and dyspareunia in a considerable proportion of the patients. The operation also seems to decrease their chances of becoming pregnant. PMID- 2313159 TI - Granulocyte transfusions: have we learned anything? PMID- 2313160 TI - Granulocyte transfusions in septic adult and newborn rats: distribution of granulocytes and effect on peripheral blood and bone marrow. AB - Granulocyte transfusions are increasingly being used as therapy for newborns with sepsis and neutropenia. We injected either group B Streptococcus or phosphate buffered saline solution intraperitoneally into adult and newborn rats. Human granulocytes, labeled with chromium 51, were transfused seven hours later. When the newborn rats were killed 13 to 19 hours after injection, they had 10(2) to 10(6) cfu/gm Streptococcus organisms in both lung and brain. Only one third of the adult rats had 10(2) to 10(4) cfu/gm Streptococcus organisms in either lung or brain. A greater proportion of the transfused granulocytes was present in lung and brain tissue of newborn rats, compared with adult rats (p less than 0.05), irrespective of infection. Granulocyte transfusion did not change the peripheral blood leukocyte count in adult rats but increased the count in newborn rats (p less than 0.05). The immature myeloid pool in the bone marrow of adult rats increased significantly with either infection or transfusion (p less than 0.01). The immature pool in newborn rats increased significantly only with infection (p greater than 0.001), although the combination of infection and transfusion also had a significant effect on the pool (p less than 0.01). Infection and both infection and transfusion, but not transfusion alone, significantly affected the mature myeloid bone marrow pool in adult and newborn rats (p less than 0.001). The depletion of the mature myeloid elements of the bone marrow in response to infection was dramatic in neonatal rats, compared with that in adult rats. Both transfused granulocytes and hematogenously spread streptococci lodge in the brains and lungs of neonatal rats more effectively than in those of adult rats. PMID- 2313161 TI - Multichannel 18-test panels: are 60% of panels abnormal by chance? AB - Current teaching concerning the frequency of abnormal results secondary to chance alone in a multichannel panel is theoretically based on the binomial distribution. However, this distribution can be used only when the probability of an abnormal result (pi) is the same for each test in the panel. In modern-day multichannel testing, pi varies from test to test and most often is less than the usually reported 0.05. On the other hand, a test such as cholesterol may have a pi level as high as 0.55. Theoretically the only distribution that can take this variability into consideration is the Lexis distribution, a form of the binomial distribution that allows for varying pi s. Since no formula is available to calculate this distribution, we wrote a computer program to generate it. We arranged 18-test panels from 203 normal patients in a frequency distribution. This was then compared with the theoretical Lexis and binomial distributions. This analysis showed that although there was a 50% chance of having one abnormality per panel and a 16% chance of having two abnormalities per panel, there was less than 4% chance of having three or more abnormalities per 18-test panel. In addition, most of the abnormalities noted were minor and were thought to be clinically unimportant. PMID- 2313162 TI - Exogenous adenine nucleotides replete endothelial cell adenosine triphosphate after oxidant injury by adenosine uptake. AB - We studied the ability of human umbilical vein endothelial cells to recover from oxidant-induced ATP depletion. When endothelial cell ATP levels were depressed to 0.93 +/- 0.14 pmol/micrograms protein (compared with 4.96 +/- 0.6 pmol/micrograms protein in control cells) by hydrogen peroxide generated with 25 mU/ml glucose glucose oxidase over 45 minutes, ATP levels returned to 1.73 +/- 0.21 pmol/micrograms protein during a 3-hour recovery period after oxidant injury ceased. When 25 microM ATP, ADP, AMP, or adenosine was added to the recovery media, intracellular ATP was significantly (p less than 0.001) increased to greater than 4.4 pmol/micrograms cell protein for each metabolite. HPLC of supernatants from oxidant-injured endothelial cells incubated with ATP, ADP, and AMP demonstrated extracellular metabolism of the adenine nucleotides to adenosine. When adenosine transport was inhibited with dipyridamole and nitrobenzylthioinosine, recovery of intracellular ATP by exogenous ATP, ADP, AMP, and adenosine was significantly (p less than 0.001) inhibited. Such cells were intact, as demonstrated by lack of LDH release. When oxidant stress was prolonged to 90 minutes, ATP depletion was irreversible, regardless of exogenously supplied adenosine; such cells demonstrated loss of cell integrity as demonstrated by release of intracellular LDH. Our results demonstrated that exogenous adenine nucleotides enhance recovery of oxidant-induced ATP depletion through metabolism to adenosine and subsequent adenosine uptake. Prolonged oxidant injury resulted in irreversible ATP depletion and loss of cell integrity that was not altered by exogenously supplied adenosine. PMID- 2313163 TI - Human C-reactive protein inhibits neutrophil chemotaxis in vitro: possible implications for the adult respiratory distress syndrome. AB - C-reactive protein (CRP) is an acute-phase protein whose serum concentration can rise dramatically after onset of inflammation. Although the precise physiologic role of elevated CRP is not known, in vitro studies have shown that CRP potentially has both pro- and anti-inflammatory properties. We hypothesized that an elevation in serum CRP may be a mechanism to control acute inflammation by down-regulating some neutrophil functions. Therefore, elevated serum CRP levels in an inflammatory state in the lung, such as the adult respiratory distress syndrome (ARDS), may have a protective effect. We observed that highly purified CRP, at levels greater than 25 micrograms/ml, inhibited both random neutrophil movement and C5a-induced chemotaxis. Neutrophils incubated with CRP showed a dose dependent diminution of migration toward chemotactic stimuli, with complete inhibition occurring at 100 micrograms/ml. This inhibitory effect of CRP on neutrophil movement was only partially reversed by washing the CRP-treated cells before assaying their chemotactic movement to 1 nmol/L C5a. Next we examined the neutrophil chemotactic activity of serum collected from normal nonsmokers, from patients at high risk for developing ARDS, and patients with ARDS. Both high-risk and ARDS serums has significantly less (p less than 0.001) neutrophil chemotactic activity than serums from normal subjects. In addition, serums from high-risk and ARDS patients had significantly elevated (p less than 0.001) levels of CRP compared with normal subjects. Anti-CRP treatment of ARDS and high-risk serum samples resulted in a significant increase (p less than 0.05) in the neutrophil chemotactic activity. Finally, addition of highly purified CRP to normal serum significantly reduces its neutrophil chemotactic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313164 TI - Measurement of lumbar CSF levels of met-enkephalin, encrypted met-enkephalin, and neuropeptide Y in normal patients and in patients with Parkinson's disease before and after autologous transplantation of adrenal medulla into the caudate nucleus. AB - The levels in lumbar cerebrospinal fluid (CSF) of neuropeptide Y (NPY), methionine enkephalin (Enk), and Enk contained in amino- and carboxy-terminus extended forms (X-Enk) were examined in nine control patients undergoing elective surgical procedures and in eight patients with advanced Parkinson's disease, before and after the autologous transplantation of adrenal medullary fragments into the right caudate nucleus. The levels of CSF Enk and X-Enk before surgery in patients with Parkinson's disease were significantly less than those observed in control patients (Enk, 166 +/- 38 vs 264 +/- 44 pg/ml; X-Enk, 794 +/- 416 vs 1497 +/- 153 pg/ml). NPY levels did not differ (221 +/- 25 vs 193 +/- 23 pg/ml). After surgery, lumbar CSF samples were taken at 6 weeks, 12 weeks, 6 months, and 9 months. Placement of adrenal medullary fragments into the striatum had no effect on the levels of NPY or Enk at any time point. The levels of X-Enk were significantly enhanced only at 12 weeks (1138 +/- 140 pg/ml) but were at presurgical levels again by 6 months. These data suggest that the transplant was not functionally contributing to the CSF levels of these peptides. PMID- 2313165 TI - Physicians and health care business. PMID- 2313167 TI - Compartment syndrome of the upper extremity. PMID- 2313166 TI - The 1989 Kentucky Hospital Smoking Policy Survey. AB - Kentucky leads the nation in percentage of smokers (32.5%), years of potential life lost due to smoking-related illness, and burley tobacco production. In view of this, we sought to determine current practice regarding smoking policies in Kentucky hospitals. Acute care and psychiatric hospitals were identified through the 1988 Kentucky Hospital Association Directory and the Paired Community Laboratory System. One hundred seven institutions were sent standardized questionnaires. An additional 16 hospitals were contacted by phone only. All mail and telephone surveys were directed towards the institution's president, administrative director, or CEO. Eighty-one (75.7%) of those contacted by mail responded to the survey. The 26 non-responding institutions were then contacted through a telephone survey. Thus, 100% of acute care hospitals in Kentucky participated in the survey. Of the 123 institutions surveyed, 110 (89.4%) have some type of smoking policy. Of those 110 hospitals with smoking policies, only 6 totally prohibited smoking on the premises. The 13 hospitals without any form of policy were queried about future plans for smoking policies. Of these, only 4 had no plans to work on a hospital smoking policy. Of the 123 hospitals surveyed, 100 do not sell tobacco products. There were no statistically significant differences between the numbers of beds, average length of stay, occupancy rate, or county populations in Kentucky hospitals that do not sell tobacco versus those hospitals that do sell tobacco.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313168 TI - Drug interactions in older adults. PMID- 2313169 TI - Resection of palatal tumours with the CO2 laser. AB - On the basis of the authors' experience with 20 patients, CO2 laser resection of palatal tumours has proved to be a good alternative to conventional surgical resection. The CO2 laser beam permits precise resection, due to only slight intra operative bleeding coupled with use of the operating microscope. Wound healing is good and post-operative pain remarkably little. PMID- 2313170 TI - Efficacy of fine needle aspiration cytology in the diagnosis of tuberculous cervical lymphadenopathy. AB - The results of a consecutive series of 1,349 fine needle aspiration (FNA) biopsies from the head and neck region of 1,193 patients has been reviewed in order to evaluate the efficacy of this method in the diagnosis of tuberculous lymphadenopathy (TBLN). Of the 108 patients whose fine needle aspiration cytology (FNAC) showed granulomatous changes, 68 had subsequent surgery and histological confirmation of the cytological appearance. Sixty-three had TBLN, thus the specificity of FNAC was 93 per cent in diagnosing tuberculous related granulomatous lymphadenopathy. One false positive FNAC was reported histologically to be metastatic mucoepidermal carcinoma. Of the 1,193 patients, 90 patients had subsequently TBLN confirmed histologically. Of these 90 patients, FNA from 69 showed granulomatous changes or acid fast bacilli (AFB), thus the sensitivity of FNAC in detecting tuberculous lymphadenopathy was 77 per cent. Fifty-two cytological smears were stained for acid fast bacilli. Nineteen (37 per cent) contained AFB. It is evident from this review that FNAC is an efficient way to detect cervical tuberculous lymphadenopathy. PMID- 2313171 TI - Audit of blood transfusion policy in head and neck surgery. AB - There is current concern about the possible adverse affects of blood transfusion on patient survival after cancer surgery. In addition, blood transfusion is associated with a low incidence of morbidity and mortality in any patient. 100 patient records have been examined retrospectively to outline the problems with blood transfusion policy in head and neck surgery. The current situation lacks standardization on a scientific basis and represents an area of resource over utilization. A new approach to this subject in head and neck surgery is proposed and a recommended 'new policy' suggested. PMID- 2313172 TI - New technique for treating pseudocyst of the auricle. AB - Although pseudocyst of the auricle is a common disease in China, its cause and mechanism are still not clear. Several methods of treatment have been advocated: repeated aspirations combined with physiotherapy, and incision and drainage with contour pressure dressing, magnetotherapy etc. In recent years, a new technique with a drainage tube inserted into the pseudocyst using a guide needle has been used in our hospital in the treatment of this condition. We report 45 cases treated by this method, none of whom had the condition previously. PMID- 2313173 TI - Kawasaki syndrome in an adult. AB - Kawasaki syndrome is a panvasculitis occurring principally in childhood. Symptoms include fever, 'strawberry tongue', cervical lymphadenopathy and dermatological signs. A rare case of Kawasaki syndrome in an adult presenting to the Otolaryngology department is reported. The clinical features of the disease are described highlighting its systemic nature. Treatment options and possible complications are discussed. PMID- 2313174 TI - Oncocytic metaplasia of the nasopharynx--unusual cause of secretory otitis media. AB - Unilateral secretory otitis media is a well recognized presenting feature of nasopharyngeal tumours. In the case described the underlying cause was of oncocytic metaplasia arising in the nasopharynx. PMID- 2313176 TI - Nasopharyngeal carcinoma with secondaries at the porta hepatis presenting as obstructive jaundice. AB - Recent reports have dispelled the previously held concept that head and neck cancer rarely metastases beyond the cervical lymph nodes. Nasopharyngeal cancer has been reported to have a higher incidence of distant metastases compared to other head and neck cancers, the common sites being bone, lung and liver. A case of nasopharyngeal carcinoma presenting as obstructive jaundice because of secondaries at the porta hepatis is presented here. PMID- 2313175 TI - Impedance tympanometry and the home environment in seven-year-old children. AB - The distribution of tympanogram types among 872 seven-year-old children from a random population sample was related to 14 features of the home environment reported by parents in a questionnaire. Parental smoking was an important determinant of middle ear underpressure and effusion, and accounted for much of the associations observed with dampness, crowding and rented accommodation. Gas cooking was associated with a higher prevalence of effusion, but a lower prevalence of underpressure; this may deserve further study. After adjustment for seasonal variation, tenure and household smokers, the weekly mean temperature in the bedrooms of 34 children with Type B tympanograms was 18.2 degrees C, compared to 17.9 degrees C for 190 children with Type A tympanograms. The equivalent figures for bedroom relative humidity were 51.8 per cent and 52.7 per cent. It is unlikely that heating or ventilation of the home is an important determinant of middle ear effusion and underpressure in this age-group. PMID- 2313177 TI - Diabetes insipidus and hypercalcaemia secondary to nasopharyngeal carcinoma. AB - We report a case of nasopharyngeal squamous carcinoma complicated by diabetes insipidus and hypercalcaemia. As there was no evidence of bony metastases we conclude that this latter finding was due to a humoral factor produced by the tumour. The management of these problems is discussed. PMID- 2313178 TI - Ovarian carcinoma metastatic to the larynx. AB - The second case of ovarian carcinoma metastatic to the larynx is presented. The sites of the primaries and metastases of previously reported cases are reviewed, and possible methods of spread discussed. PMID- 2313179 TI - Detection of extrinsic bronchial compression during foreign body removal by pulse oximetry. AB - A case of stridor is described which was due to the presence of a foreign body in the larynx of an infant. Following partial removal, compression of the right main bronchus was detected because of continuing low arterial oxygen saturation. The use of pulse oximetry allowed this complication to be identified, and the advantages of this method of monitoring are discussed. PMID- 2313180 TI - Respiratory problems in acromegaly. AB - Death from respiratory causes in acromegaly is three times more common than in the general population and is most often the result of upper airways obstruction, although less commonly pulmonary dysfunction and disturbance of the central nervous system may occur. These factors may be found alone or in combination. Despite several reports of laryngeal involvement, upper airway obstruction in acromegaly is usually regarded as being due to macroglossia and pharyngeal soft tissue hypertrophy. We present four cases of acromegaly in which tracheostomy was required for laryngeal obstruction, with a review of the literature concerning the nature of respiratory problems in acromegaly. PMID- 2313181 TI - Parathyroid cyst: report of case in the mediastinum. AB - Though a rare lesion a parathyroid cyst is of clinical significance because it usually mimics a thyroid cyst and can be associated with hyperparathyroidism. The cyst can be ectopic with location in the lateral neck or in the mediastinum and therefore constitutes a differential diagnosis to a branchial or thymic cyst. A case report of a mediastinal parathyroid cyst without hyperparathyroidism is presented. Fine needle aspiration with parathyroid hormone assay on the cyst fluid will reveal the correct diagnosis. Surgical removal of the cyst is recommended, and hyperparathyroidism should be considered. PMID- 2313182 TI - Adenoidal hypertrophy as the presenting feature of HIV infection. AB - A case of symptomatic recurrent adenoidal hypertrophy, as the presenting feature of HIV infection in a haemophiliac child, is reported. The incidence of non malignant nasopharyngeal lymphoid hyperplasia in HIV infection is examined and the relevance of the histological appearance is discussed in relation to progression of disease. PMID- 2313184 TI - The Learning Mystique. PMID- 2313183 TI - Carcinoma of the nasal vestibule: report of 12 cases. AB - Carcinoma of the nasal vestibule has an individual clinical character; in this retrospective analysis the data of 12 consecutive patients are reported. Small lesions were treated by surgical resection and larger tumours by intra-arterial chemotherapy (IAC) followed by external beam radiotherapy. One patient had a recurrence which was successfully treated surgically; six had previous or subsequent malignancies. The results of the most recent series reported in the literature are reviewed and the rationale of the IAC approach is discussed. The reported treatment policy seems effective in achieving the highest cure rate with the best functional results. PMID- 2313185 TI - The Newtonian Mechanistic paradigm, special education, and contours of alternatives: an overview. PMID- 2313187 TI - Family communication and children's learning disabilities: evidence for Coles's theory of interactivity. PMID- 2313186 TI - The general education initiative and children with special needs: a false dilemma in the face of true problems. PMID- 2313188 TI - A word identification strategy for adolescents with learning disabilities. AB - Students with learning disabilities frequently experience difficulty on reading tasks. This difficulty is heightened for adolescents with learning disabilities who are responsible for reading and understanding materials written at several grade levels above their reading ability. Word identification becomes an increasingly important skill for these students, especially when confronted with unfamiliar, polysyllabic words. The present study investigated the effects of training 12 adolescents with learning disabilities in a word identification strategy, DISSECT. The results indicated that the strategy was effective in reducing reading errors for all subjects. However, it was found that increases in word identification differentially affected reading comprehension and indicate the need for separate and/or simultaneous attention to comprehension processes. PMID- 2313189 TI - Learning to solve a problem: a microanalysis of the solution strategies of children with learning disabilities. AB - Ten subjects with learning disabilities and 10 normally achieving subjects, aged 10-5 to 12-5 years, were videotaped while attempting to solve the Tower of Hanoi problem (see Karat, 1982; Piaget, 1976; Simon, 1975). A microanalysis of their problem-solving activities provided a descriptive taxonomy used to analyze what, in fact, individual subjects did when constructing a solution strategy, and to categorize and compare changes in strategy. The results indicated that as a group the normally achieving subjects reached more sophisticated levels of strategy use (p less than .05). However, if the focus of the comparison is on an analysis of how learning proceeded in individuals, then the subjects with learning disabilities appear to be similar to the normally achieving subjects. There was no evidence in these subjects of the popular conception that individuals with learning disabilities are inactive, passive, or maladaptive in their attempts to learn to solve a problem. PMID- 2313190 TI - Motivational readiness and the participation of children with learning and behavior problems in psychoeducational decision making. AB - Efficacy of a brief cognitive-affective intervention to enhance motivational readiness for participating in a psychoeducational decision-making conference was explored. Although outcomes specific to the preconference intervention were not found, findings of relevance to the hypothesized positive relationship between motivational readiness and actual participation in decision making are reported. The positive and negative findings are discussed in terms of implications for enhancing motivational readiness and for understanding the limited impact of skill training to improve participation and decision making. PMID- 2313191 TI - Self-perceptions, motivation, and adjustment in children with learning disabilities: a multiple group comparison study. AB - This study examined the self-perceptions, motivational orientations, and classroom adjustment of children with learning disabilities (LD), matched-IQ non LD, randomly selected non-LD, and low achieving children. Elementary-age children (N = 148; 37 from each group) completed domain-specific measures of their self concepts, perceptions of control, and motivation. Teachers rated children on motivational and competence indices and classroom behavioral adjustment. Comparisons among groups indicated that children with LD were lower in perceived cognitive competence and academic self-regulation relative to the nondisabled control groups, but were comparable to the low achieving children. Children with LD were most likely to perceive academic outcomes as controlled by powerful others. No group differences were found for general self-perceptions of control or competence. Teacher ratings of children with LD were more discrepant from those of comparison groups than were self-ratings of children with LD. The results suggest the need for matched-IQ and low achieving control groups in research on children with LD. The origin and role of both environmental inputs and self-perceptions in the adjustment of students with LD are discussed. PMID- 2313192 TI - Faculty willingness to accommodate students with learning disabilities: a comparison among academic divisions. AB - One hundred seven faculty members at a northwestern college responded to a questionnaire devised to assess faculty willingness to provide students with learning disabilities instructional, assignment, examination, and special assistance accommodations. Faculty responses to the questionnaire were analyzed to determine if differences existed among faculty in the colleges of Education, Business, and Arts and Sciences. Results indicate that, in general, faculty were willing to provide students with learning disabilities accommodations, but that differences exist among the three academic divisions as to faculty willingness to provide students accommodations. The implications of these results for colleges and universities and future research are discussed. PMID- 2313193 TI - Story grammar and comprehension and production of narrative prose by students with learning disabilities. AB - This study investigated both quantitative and qualitative differences between subjects with and without learning disabilities (LD) across three grade levels on two tasks requiring active processing of story grammar. There was no evidence, for either task, of developmental differences in relation to either story comprehension or production. However, there were significant differences between students with LD and normally achieving students in the amount as well as the type of information included in the retellings and written stories. The results provide support for the hypothesis that students with LD have acquired a rudimentary but not fully developed schema for narrative prose. PMID- 2313194 TI - Reading vowels in Kannada script. AB - Among speakers of English, a greater number of vowels are misread by poor readers than are consonants. This is thought to be due to the complex way that vowels are represented in the alphabetic script. In Kannada, which has a phonetically regular script, children learn to read using a clear set of rules with respect to vowels and consonants. The purpose of this study was to determine the nature of misreadings of vowels by two groups, good readers and poor readers of Kannada. The poor readers misread a large number of items in two lists of syllables and words. Both groups misread vowels in equal proportion to their total number of misreadings. The results are discussed. PMID- 2313195 TI - Rapid intracellular transport of LDL-derived cholesterol to the plasma membrane in cultured fibroblasts. AB - The kinetics of low density lipoprotein (LDL) cholesterol transport to the plasma membrane of Chinese hamster ovary (CHO) cells was studied. LDL was reconstituted with [3H]cholesteryl linoleate and added to CHO cells in a pulse-chase experiment. The internalization and lysosomal cleavage of reconstituted LDL (rLDL) [3H]cholesteryl linoleate to free [3H]cholesterol occurred with a half time of 37 min after a 30-min lag. The rate of transport of released [3H]cholesterol to the plasma membrane was measured by brief (20-30 sec) cholesterol oxidase treatment of intact, adherent cells: the half-time of transport was 42 min. The similarity in the rate of free cholesterol release from rLDL and transport of this cholesterol to the plasma membrane suggests very rapid transport of rLDL cholesterol from the lysosome to the plasma membrane. Cells were shown to be intact throughout the cholesterol oxidase treatment by the absence of cell-derived lactate dehydrogenase (LDH) activity or K+ in the assay buffer. PMID- 2313196 TI - Increased production of apolipoprotein B and its lipoproteins by oleic acid in Caco-2 cells. AB - The production of lipids, apolipoproteins (apo), and lipoproteins induced by oleic acid has been examined in Caco-2 cells. The rates of accumulation in the control medium of 15-day-old Caco-2 cells of triglycerides, unesterified cholesterol, and cholesteryl esters were 102 +/- 8, 73 +/- 5, and 11 +/- 1 ng/mg cell protein/h, respectively; the accumulation rates for apolipoproteins A-I, B, C-III, and E were 111 +/- 9, 53 +/- 4, 13 +/- 1, and 63 +/- 4 ng/mg cell protein/h, respectively. Whereas apolipoproteins A-IV and C-II were detected by immunoblotting, apoA-II was absent in most culture media. In contrast to an early production of apolipoproteins A-I and E occurring 2 days after plating, the apoB expression appeared to be differentiation-dependent and was not measurable in the medium until the sixth day post-confluency. In the control medium, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and lipid-poor very high density lipoproteins (VHDL) accounted for 12%, 46%, 18%, and 24% of the total lipid and apolipoprotein contents, respectively. The triglyceride-rich VLDL contained mainly apoE (75%) and apoB (23%), while the protein moiety of LDL was composed of apoB (59%), apoE (20%), apoA-I (15%), and apoC-III (6%). The cholesterol-rich HDL contained mainly apoA-I (69%) and apoE (27%). In the control medium, major portions of apolipoproteins B and C-III (93-97%) were present in LDL, whereas the main parts of apoA-I (92%) and apoE (76%) were associated with HDL and VHDL. Oleate increased the production of triglycerides 10-fold, cholesteryl esters 7-fold, and apoB 2- to 4-fold. There was also a moderate increase (39%) in the production of apoC-III but no significant changes in those of apolipoproteins A-I and E. These increases were reflected mainly in a 55-fold elevation in the concentration of VLDL, and a 2-fold increase in the level of LDL; there were no significant changes in HDL and VHDL. VLDL contained the major parts of total neutral lipids (74-86%), apoB (65%), apoC-III (81%) and apoE (58%). In the presence of oleate, the VLDL, LDL, HDL, and VHDL accounted for 76%, 15%, 3%, and 6% of the total lipoproteins, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313197 TI - Highly polymorphic apolipoprotein A-IV locus in the baboon. AB - Apolipoprotein A-IV is found in mesenteric lymph chylomicrons, very low density lipoprotein particles, high density lipoprotein particles, and in the lipoprotein free fraction of plasma. Apolipoprotein A-IV is polymorphic in a variety of species including human, dog, and horse. Efforts to estimate the impact of apolipoprotein A-IV structural variation on quantitative lipid levels in humans have been limited by the low frequency of the less common alleles. In the baboon, Papio hamadryas anubis, we have found apolipoprotein A-IV to be highly variable at the protein level with five alleles appearing at polymorphic frequency. We have confirmed the autosomal codominant inheritance of these five alleles in pedigreed baboons. The baboon has been shown to be a suitable animal model for the study of atherosclerosis, and the existence of a common, multi-allele apolipoprotein A-IV polymorphism in the baboon may be useful in elucidating the role of apolipoprotein A-IV in lipid metabolism. PMID- 2313199 TI - Analytical isoelectric focusing with immobilized pH gradients of human apolipoprotein E from very low density lipoproteins and total plasma. AB - A method for analytical isoelectric focusing (IEF) of apolipoprotein E (apoE) in immobilized pH gradients (IPG) and immunodetection of the separated isoforms has been developed for use with either very low density lipoproteins (VLDL) or whole plasma. Both VLDL and plasma were sequentially delipidated with 1,4-dioxane, acetone-ethanol, and ether. Neuraminidase treatment preceded the delipidation when required. Using preformed plates, pH 5.0-6.0 (LKB, Bromma) after rehydration with 6 M urea and dextran T-10, the IPG focusing pattern of the common isoforms (E2, E3, E4) was found to be equivalent to conventional IEF with the added resolution of the E4 disialo form. The use of self-poured narrower gradients permitted the further resolution of the E4 monosialo form, a previously unrecognized heterogeneity of the E2, E3, and E4 monosialo isoforms and differentiation of the apoE2** mutant; all of these forms comigrate with the common isoproteins in conventional IEF. Finally, the conditions for IPG of whole plasma using apoE monoclonal antibodies and enzyme-conjugated anti-mouse IgG for detection were established. Thus, IPG focusing is shown to be a powerful method for resolution of the apoE sialoforms and apoE mutant forms. The method has important implications in accurate and diagnostic phenotyping. Moreover, it is a convenient method for phenotyping which requires only very small volumes of plasma. PMID- 2313198 TI - Lipolysis of menhaden oil triacylglycerols and the corresponding fatty acid alkyl esters by pancreatic lipase in vitro: a reexamination. AB - In order to distinguish between possible fatty acid differences during lumenal lipolysis and cellular absorption, we have reinvestigated the in vitro hydrolysis of menhaden oil and its alkyl esters by pancreatic lipase. For this purpose we incubated menhaden oil or its fatty acid methyl and ethyl esters with porcine pancreatic lipase in the presence of bile salts and determined the composition of the released free fatty acids, monoacylglycerols, diacylglycerols, and residual triacylglycerols, or the free fatty acids and residual alkyl esters, respectively, by thin-layer and gas-liquid chromatography. There was significant discrimination against the delta 4- to delta 7-unsaturated fatty acids of both medium and long chain lengths during the hydrolysis of menhaden oil and its fatty acid ethyl esters. In general, the ethyl esters were hydrolyzed 10-50 times more slowly than the corresponding glyceryl esters, depending on the exact ratio of the two substrate types. None of the triacylglycerols or ethyl esters, however, was completely resistant to hydrolysis resulting in an eventual cleavage of all the alkyl esters and presumably all the primary ester bonds in the triacylglycerol molecules. Since the rate of release of the least resistant fatty acid exceeded that of the most resistant acid by only a factor of 6, it is concluded that in the presence of a large excess of lipase the liberated fatty acids would approach the composition of the dietary alkyl or glyceryl esters, as observed during lumenal lipolysis (Yang, L.-Y., A. Kuksis, and J. J. Myher. 1989. Biochem. Cell Biol. 67: 192-204). PMID- 2313200 TI - A facile synthesis of [14C] epicholesterol. AB - A facile procedure is described for the preparation of [14C]epicholesterol from [14C]cholesterol. Cholesterol is first converted to cholesteryl mesylate, which is treated with cesium acetate and 18-crown-6 in refluxing toluene to give epicholesteryl acetate. The latter is hydrolyzed, without isolation, with potassium hydroxide in tetrahydrofuran-methanol to give epicholesterol, which is obtained in pure form by preparative thin-layer chromatography. PMID- 2313201 TI - Size and shape determination of fixed chylomicrons and emulsions with fluid or solid surfaces by three-dimensional analysis of shadows. AB - Chylomicrons and chylomicron-sized emulsions are spherical particles in suspension but their shape and apparent size may be distorted by electron microscopy processing. To assess adsorption to grids, flattening, and shrinkage, chylomicrons and emulsions were fixed with osmium tetroxide and together with polystyrene beads were shadowed with platinum. Vertical profiles projected from particle shadows indicated that the chylomicrons and emulsions were slightly shrunken, slightly truncated, oblate spheroids while the polystyrene beads were spheres. Particle diameters were corrected by assuming that volumes of oblate spheroids on the grid surface were equal to volumes of spheres in the original lipid suspension. Because of the compensating effects of shrinkage (decreases diameter) and flattening (increases diameter) the differences between the means of measured diameters and corrected diameters were less than or equal to 5%. PMID- 2313202 TI - Identification of lipoprotein lipase immunoreactive protein in pre- and postheparin plasma from normal subjects and patients with type I hyperlipoproteinemia. AB - Postheparin plasma is a convenient source for the measurement of lipoprotein lipase (LPL) in humans. Previous studies have focused on the measurement of LPL catalytic activity, and have been unable to conveniently measure the LPL protein or identify possibly different plasma forms of the enzyme. Pre- and postheparin plasma was treated with a highly specific antibody raised against bovine milk LPL and the immunoprecipitate was analyzed by Western blotting. In normal subjects there were several species of LPL in plasma. A 56 kD protein increased after heparin injection, and likely represented active LPL. The anti-LPL antibody reacted specifically with this 56 kD protein, and also reacted specifically with proteins at 52 kD, 69 kD, as well as a 20 kD breakdown product. In addition, using peptide mapping, the 56 kD protein was structurally similar to the 52 and 69 kD LPL proteins. The antibodies were affinity purified, biotinylated, and used to quantitate LPL immunoreactive mass using an enzyme-linked immunosorbent assay (ELISA). LPL immunoreactive mass was present in all subjects in preheparin plasma. In postheparin plasma, five patients with type I hyperlipoproteinemia displayed decreased LPL immunoreactive mass when compared to normal subjects, although there was a wide range of specific activity of the small amount of enzyme present. When the LPL from the plasma of the patients was immunoprecipitated and Western blotted, there was considerable heterogeneity in the appearance of the LPL forms, and an overall decrease in LPL protein. Thus, several different immunoreactive LPL proteins were present in pre- and postheparin plasma. In preheparin plasma, as well as in patients with type I hyperlipoproteinemia, there was decreased immunoreactive LPL protein, and the LPL protein that was present was of low specific activity. PMID- 2313203 TI - Low density lipoprotein-induced growth of U937 cells: a novel method to determine the receptor binding of low density lipoprotein. AB - U937 is a monocytic cell-line originally derived from a histiocytic lymphoma. In serum-free medium the growth of U937 cells was stimulated by addition of low density lipoprotein (LDL). Methylation of LDL impaired its ability to be taken up in U937 cells as well as the capacity to stimulate the growth of these cells. Pretreatment of U937 cells with a monoclonal antibody against the LDL receptor was also found to completely block the growth-promoting effect of LDL. Exposure of U937 cells to liposomes with a lipid composition similar to that of LDL did not stimulate the growth rate. These findings demonstrate that growth of U937 cells under serum-free conditions is related to the amount of LDL ingested by the cells and that this uptake is mediated by binding of LDL to the LDL receptor. To determine if LDL-induced growth of U937 cells can be used to identify LDL with decreased binding to the LDL receptor, U937 cells were incubated with LDL isolated from a patient with familial defective apolipoprotein B-100 and from subjects with various lipoprotein phenotypes. LDL containing defective apolipoprotein B-100 was found to be less than half as effective as LDL from normolipidemic controls in stimulating growth of U937 cells. LDL isolated from patients with hyperlipoproteinemia type IIa and IV did not differ from normal LDL in their ability to promote growth of U937 cells. The present results suggest that LDL-induced growth of U937 cells may be used as an assay to identify defective receptor binding of LDL. PMID- 2313204 TI - Genetic heterogeneity in familial dysbetalipoproteinemia. The E2(lys146----gln) variant results in a dominant mode of inheritance. AB - As determined by isoelectric focusing, most patients with familial dysbetalipoproteinemia (FD) exhibit the homozygous apolipoprotein (apo) E2E2 phenotype. Only rarely does FD develop in the more common heterozygous phenotypes E3E2 or E4E2. In fact, only 1 to 4% of the E2E2 homozygotes will develop FD. We wondered whether this reduced penetrance of FD in E2E2 homozygotes could be due to additional heterogeneity in the APOE*2 allele. In the literature a number of different mutations causing an E2 isoelectric focusing variant have been described. To study the genetic heterogeneity of the APOE gene, hybridization of enzymatically amplified genomic DNA with mutation-specific oligonucleotide probes was applied. All FD patients (n = 40) with the E2E2 phenotype appeared to be homozygous for the common E2(arg158----cys) mutation. However, all three unrelated patients with the E3E2 phenotype exhibited the rare E2(lys146----gln) mutation due to an A----C substitution at nucleotide position 3,847 of the APOE gene. This mutation was not found among normolipidemic individuals with the E2E2 (n = 13) or E3E2 phenotype (n = 120) selected from a random population sample. Family studies of the three probands heterozygous for the E*2(lys146----gln) allele showed that this rare allele predisposes to FD with high penetrance. We conclude that FD is a genetically heterogeneous disease entity, displaying a recessive mode of inheritance with strongly reduced penetrance in case of the common E2(arg158----cys) variant and with a dominant mode of inheritance with high penetrance in case of the rare E2(lys146----gln) mutant. It should be noted that in this dominant form presymptomatic diagnosis is possible. PMID- 2313205 TI - Structural alterations in lecithin-cholesterol vesicles following interactions with monomeric and micellar bile salts: physical-chemical basis for subselection of biliary lecithin species and aggregative states of biliary lipids during bile formation. AB - Using complementary physical-chemical methods including turbidimetry, quasielastic light scattering, gel filtration, and phase analysis, we examined the interactions between dilute concentrations of the common bile salt, taurochenodeoxycholate (TCDC), and uni- and multilamellar vesicles (MLVs) composed of defined molecular species of lecithin (L) and varying contents of cholesterol (Ch). Dissolution rates of MLVs with micellar TCDC, as assessed by turbidimetry, were more rapid with vesicles composed of sn-1 palmitoyl species, typical of biliary L, compared with those composed of the more hydrophobic sn-1 stearoyl species. Incorporation of Ch retarded MLV dissolution rates in proportion to the Ch content, and only at high Ch contents were dissolution rates appreciably influenced by the sn-2 fatty acid composition of L. When MLVs contained Ch in amounts characteristic of intracellular membranes (Ch/L approximately 0.1), the dissolution rates of the individual L species by TCDC accurately predicted the steady state L composition of human bile. TCDC interacted with small unilamellar L/Ch vesicles (SUVs) at concentrations well below, as well as appreciably above, its critical micellar concentration. In accordance with the TCDC-egg yolk L-H2O phase diagram, perimicellar concentrations of TCDC interacted with SUVs to form aggregates that were approximately twice the size of the SUVs. These were consistent with the formation of a dispersed hexagonal (rod-like) phase, which co-existed with aqueous bile salt (BS) monomers and either micellar or unilamellar SUV phases. Micellar TCDC completely solubilized SUVs as mixed micelles, putatively via this transient hexagonal phase. With modest Ch-supersaturation, dissolution was followed by the reemergence of a new vesicle population that coexisted metastably with mixed micelles. With high Ch supersaturation, TCDC extracted L and Ch molecules from SUVs in different proportions to form Ch-supersaturated mixed micelles and Ch-enriched SUVs, in accordance with the metastable phase diagram. These experiments are consistent with the hypothesis that sn-1 palmitoyl L species are subselected for bile, in part, by physical-chemical interactions of intracellular BS concentrations with Ch-poor membranes and that the subsequent evolution of Ch-rich vesicles and Ch-saturated mixed micelles occurs via a transitional hexagonal (rod) phase. These liquid-crystalline states are likely to be transient in Ch-unsaturated biles, but may persist in Ch-supersaturated human biles because of their high Ch contents which retard or inhibit these phase transitions. PMID- 2313206 TI - Regulation of bile acid synthesis. IV. Interrelationship between cholesterol and bile acid biosynthesis pathways. AB - Under most experimental conditions, the activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase) and cholesterol 7 alpha-hydroxylase, change together in parallel directions. It has been suggested that newly synthesized cholesterol may be the preferred substrate for cholesterol 7 alpha-hydroxylase, which may account for the observed synchronous behavior of the two enzymes. To test this hypothesis, mevinolinic acid, a potent competitive inhibitor of HMG-CoA reductase, was administered as a single intravenous bolus (10 mg/kg) to rats with a chronic bile fistula. Bile acid synthesis was determined following inhibition of HMG-CoA reductase by mevinolinic acid over a 27-h time course and specific activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase were determined in liver microsomes. At 3, 6, and 27 h after a bolus dose of mevinolinic acid, bile acid synthesis was reduced by 54 +/- 5%, 42 +/- 8%, and 23 +/- 13%, respectively, from preinfusion baseline. Within 30 min after administration of mevinolinic acid, HMG-CoA reductase activity was inhibited by at least 87%. At 0.5, 1.5, 3, 6, and 27 h after mevinolinic acid injection, cholesterol 7 alpha-hydroxylase activity was decreased by 6%, 25%, 54%, 41%, and 17%, respectively. By 27 h, the activities of both enzymes had returned to baseline levels. The reduction of bile acid synthesis correlated closely with the observed changes in the activities of cholesterol 7 alpha-hydroxylase. In vitro addition of mevinolinic acid (up to 20 microM) to rat liver microsomes failed to inhibit cholesterol 7 alpha-hydroxylase activity, suggesting no direct effect of mevinolinic acid on enzyme activity. When a bolus dose of mevinolinic acid was coupled with a continuous infusion of mevalonate, the product of the reaction catalyzed by HMG-CoA reductase, the mevinolinic acid-induced decrease in cholesterol 7 alpha-hydroxylase activity and bile acid synthesis was prevented. The results of this study provide evidence that, under the experimental conditions described, there is a linkage between the rates of cholesterol synthesis and the activities of cholesterol 7 alpha-hydroxylase. The data also emphasize the importance of the newly synthesized cholesterol in the regulation of cholesterol 7 alpha-hydroxylase activity. PMID- 2313207 TI - [Danazol and antithrombin III deficiency]. AB - The study concerned 7 subjects (3 men, 4 women) with nonfamilial antithrombin III deficit which, in the absence of known causes of acquired deficiency, was defined as "sporadic". Danazol (an attenuated synthetic androgen) already shown to be capable of compensating for a lack of certain antiproteases, was given in doses of 200 mg 3 times per day for 10 days, resulting in a rapid rise (mean 21.2%) in antithrombin III values. Unlike results reported in the literature in cases of familial antithrombin III deficit, the levels did not drop below their initial values despite discontinuance of the drug but unexpectedly remained high and even shows a slight subsequent rise. Although our study was limited to 11 cases, these data seem worthy of being reported, with the prospect of other confirmations concerning either this sort of "sporadic" antithrombin III deficit or the favorable effect of Danazol, even at long term. PMID- 2313208 TI - [Study of venous inflow and outflow using mercury gauge venous occlusion plethysmography during pregnancy]. AB - Changes due to hormone activity and caval compression by the uterus were noted in venous hemodynamics of the lower limbs during pregnancy. The purpose of the study was to search for a possible incidence of these modifications on venous inflow ant outflow during mercury strain gauge plethysmography (fig. 1). A total of 183 subjects were distributed into 4 groups: (table I) nonpregnant women of childbearing age (controls = C) and women of the first (G1), second (G2) and third (G3) trimesters of gestation. Women with a history of phlebitis or pronounced varicosis were excluded. The figures for venous filling (table II, III et IV) (delta V) were 3.2 (C), 3.1 (G1), 2.64 (G2) and 2.04 (G3). There was a significant (P less than 0.001) reduction in G3 (and left-sided G2) delta V compared to that of controls. Maximum venous outflow (MVO) was 125.3 (G1), 123.7 (G2) and 123.5 (G3), showing no significant difference with controls (125.1). It is concluded that no significant change in MVO occurred during pregnancy, whereas there was a decrease in delta approximately greater than V during the third trimester. These results suggest that the latter parameter should not be considered as a criterion for diagnosis of phlebitis in the pregnant woman. PMID- 2313209 TI - [Acute aortic dissection and peripheral ischemia. Diagnostic and therapeutic problems. Remote control using nuclear magnetic resonance]. AB - This study concerns 7 cases of acute aortic dissection associated with visceral and/or lower limb ischemia. Only those cases are included which raised diagnostic and therapeutic problems. Patients were excluded who had purely angiographic involvement of an aortic branch and minor rapidly resolving ischemic syndromes. Five of the 7 patients presented type B (type III or distal) and 2 type A (type I or proximal) dissection. All patients received anti-hypertensor medical treatment. All but one had undergone surgery at least once at the acute stage. Five had been followed up and monitored by magnetic resonance imaging (MRI). One type A and 4 type B dissections were thus reviewed between the 15th month and the 9th year. Diagnostically, aortography was found to be inaccurate twice because of incomplete exploration of the thoracoabdominal aorta. Therapeutically, a case of intraoperative death occurred during replacement of the ascending aorta. Thus, out of the 6 patients who survived the acute stage, 4 are alive and asymptomatic, one has been lost sight of and the other died in year 5 after surgery for chronic dissecting aneurysm of the aortic arch. Among the 5 patients examined by MRI, 4 presented aortic ectasia, chronic dissecting aneurysm of the aortic arch and/or a descending aorta with a diameter between 45 and 65 mm. The patient with subnormal aortic diameter had his ascending aorta replaced (the follow-up period at this writing is only 27 months). Among 3 patients who were examined twice, one showed improvement after a year's interval, with a 5-mm increase in the caliber of the dissected aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313210 TI - [Diabetic cheiroarthropathy. Microcirculatory aspects]. AB - Diabetic cheiroarthropathy (DCA) or pseudosclerodermatous hand of the diabetic is characterized by nonpainful limited extension of the proximal metacarpophalangeal and/or interphalangeal joints with spontaneous flexum of the fingers. The mechanism of lesion formation is poorly known but apparently associates neurogenic, vascular and cutaneous phenomena. Fifteen patients with DCA (9 men, 6 women; range 20-74 years) were studied by capillaroscopy, photoplethysmography and skin biopsy. Eleven had type 1 diabetes and 4 type 2 over periods ranging from 1 to 42 years (mean 19.9 years). Diabetic retinopathy was noted 10/15 times, nephropathy 5/15 times and neuropathy of the lower limbs 13/15 times. All patients had at least one of these abnormalities. In capillaroscopy, "Shoal of fish" features of diabetic microangiopathy were found only 4 times, but minor dystrophy was noted in 12 cases. In digital photoplethysmography, a drop in digital systolic pressure or an increase in pulse time was noted in 5 cases. The Hillestad test was less than or equal to 2 in 8 patients. Histological study showed constant dermal collagenous fibrosis in diseased skin, which was also found in normal skin in 6/13 patients. PAS staining showed a thickening of vascular basal membrane 14/15 times in diseased skin and 11/13 times in normal skin. The relation between DCA and microangiopathy is discussed in terms of collagen metabolism abnormalities observed during diabetes. PMID- 2313211 TI - [Epidemiologic aspects of polyarterial pathology]. AB - With the considerable technical progress in vascular investigations made in the last decade, evaluation of multifocal ischemic pathology (MIP) has become easier and allows better assessment of strategy for reperfusion. In vascular surgery, 50% of post-operative mortality and morbidity are related to coronary heart disease (CHD). Epidemiologic data, not biased by specific recruitment of medical and surgical departments, are needed to assessing the real incidence of MIP. Different clinical date have already shown the problem of MIP: the post-operative cardiac mortality rate in vascular surgery has been evaluated at between 0.9% and 3.5% for abdominal aortic aneurysms and 0.3% and 3.2% for peripheral vascular disease (PVD) according to recent statistics (2, 7, 10, 12, 21) (Table I). The total cardiac mortality rate is between 1% and 2% for vascular surgery and is 0.2% for general surgery (8). Thus, though early post-operative over-risk in vascular surgery is not very high, the long term-prognosis is far more impaired: 25% to 55% of patients will die within 10 years after vascular surgery (4, 10, 13, 20). Hertzer, using systematic pre-operative coronary angiograms, found significant coronary stenosis in 57% of patients referred for vascular surgery (11). POPULATION AND METHODS: This study was performed in a representative sample taken from an ongoing prospective survey of 10,446 council employees in Marseille (5,177 men (M.), 5,269 women (W.)). This sample of 1,883 M. and 1,212 W. (mean age: 42.3 +/- 9 for M., 44.9 +/- 11 for W., range 25-65 years) was submitted to a detailed questionnaire on personal and family history of CHD, risk factors and symptoms of CHD (22), and to a physical examination including height, weight and blood pressure measurements. Every subject underwent an ECG recording and a dietetic (5) and psychologic (1) interview, and a blood sample was taken for plasma glucose, total cholesterol and lipoprotein assay. According to epidemiologic data, the prevalence of MIP appears to be lower as compared to clinical data. Undoubtedly, clinical data from surgical departments overestimate the true prevalence of MIP since patients referred for surgical therapy are usually suffering from more advanced pathology. Epidemiology, mainly based on non invasive data probably underestimates the prevalence of MIP but confirms the highest prevalence of CHD as compared to prevalence of other localisations of atherosclerosis and shows CHD as being the earliest localisation of vascular ischemic lesions in most cases. When unifocal ischemic pathology (UIP) and MIP are compared, risk factors are the same, although different proportions of patients are concerned with some of them: in MIP, age is still the major risk factor, whereas smoking in M. and overweight in W. seem to be more frequent than in UIP. RESULTS: Sixty-eight cases (5%) of ischemic pathology were found in men and 47 cases (4%) in women, with 4.1% cases of unifocal ischemic pathology (UIP) in M. and 3.3% in W... PMID- 2313212 TI - [Evaluation of coronary risk in arterial surgery]. AB - To evaluate the incidence of coronary artery disease in peripheral vascular surgery, three groups of patients (table. I) were studied retrospectively: 286 patients who had vascular surgery with no concern for the location of arterial lesions (group I); 130 patients electively operated for infra-renal abdominal aortic aneurysm (group II); and 120 patients who had 139 carotid endarterectomies (group III). The frequency of cardiac history (table II) evaluated in the three groups of patients, was respectively 42.6%, 41.4.% and 27.5%. Operative mortality in the three groups was respectively 6%, 3.8% and 1%. In group I, mortality of cardiac origin was 2.2% and cardiac morbidity 7%. In this group, analysis of results showed that the existence of cardiac history is a significant risk factor (table III) for the mortality and incidence of cardiac complications (p less than 0.005). In groups II et III, operative mortality of cardiac origin was respectively 1.5% and 0%; cardiac morbidity was respectively 4.6 and 2.2%. On the basis of this analysis, we can conclude that cardiac complications are the main cause of mortality and morbidity in peripheral vascular surgery and that the existence of cardiac history is a significant predictive factor in evaluation of operative risk in vascular surgery. PMID- 2313213 TI - [Natural and corrected history of obliterative radiation arteritis. Apropos of 14 case reports]. AB - Analysis of a series of 14 cases of obliterative radiation arteriopathy was carried out in order to study the clinical features, symptomatology and the results of appropriate therapy. This demonstrated that the diagnosis is often missed due to the time interval since radiation and that on the contrary the diagnosis should only be considered in precise circumstances in terms of the delay and localisation superimposed on the irradiated zone with respect of other non-irradiated zones. Diagnosis requires double investigation both in terms of the arterial disease and associated post-radiation lesions and also in terms of the malignant disease, its progression and treatment. Arterial surgery is fraught with difficulty due to sclerosis and other specific problems: skin closure problems, and in the case of a prosthesis, anastomotic breakdown and superinfection. These dangers should not be underestimated even if in the series presented there were no serious postoperative complications. The indication for surgery should therefore be carefully considered: best avoided in asymptomatic forms, dilatation for short lesions and revascularisation for widespread and symptomatic lesions, while choosing the most appropriate revascularisation procedure. Radiation arteritis should be better understood by radiotherapists who should pay attention to preventive measures and advise systematic screening after three years. PMID- 2313214 TI - Oxytocin biosynthesis in serum-free cultures of human granulosa cells. AB - Human granulosa cells were collected from preovulatory follicles during follicular puncture for in-vitro fertilization. They were cultured in serum-free medium supplemented with ascorbic acid. Using a combination of high-performance liquid chromatography and radioimmunoassay, the oxytocin material present in the cell extracts and secreted into the medium was identified. When cells were deprived of ascorbate, intermediary forms resulting of the post-translational processing of pro-oxytocin/neurophysin were detected. These data demonstrate that oxytocin biosynthesis occurs in human granulosa cells. PMID- 2313215 TI - Sex differences in hepatic cytochrome P-450 monooxygenase activities in rainbow trout during an annual reproductive cycle. AB - Hepatic microsomal cytochrome P-450 monooxygenase activities were investigated in rainbow trout during an annual reproductive cycle. The fish were kept in tanks supplied with fresh water at a constant temperature of 10 degrees C. The daily light and darkness cycle was adjusted to follow the natural photoperiod. Sampling was performed once every month for 1 year. Higher benzo(a)pyrene-hydroxylase (or aryl hydrocarbon hydroxylase; AHH), ethoxycoumarin-O-deethylase (ECOD) and ethylmorphine-N-demethylase (END) activities and cytochrome P-450 content were found during the late stage of sexual development in rainbow trout. When monooxygenase activities were expressed on a per cytochrome P-450 basis, sex dependent differences were observed only for AHH and ECOD activities. It was thus found that sex-dependent variations of END were closely correlated with the total amount of cytochrome P-450. The results indicate that differences exist in hepatic cytochrome P-450 isoenzyme patterns between the sexes in rainbow trout. The similarity of the annual pattern of plasma levels of oestradiol and testosterone to that of sex-dependent differences in the cytochrome P-450 monooxygenases support the contention that sex steroids play a role in regulating the cytochrome P-450 system. PMID- 2313216 TI - Participation of tri-iodothyronine and metabolic clearance rate in the inhibition of growth hormone secretion in thyroxine-treated domestic fowl. AB - Surgical thyroidectomy increases basal and TRH-induced GH concentrations in the peripheral plasma of immature domestic fowl. Replacement therapy with thyroxine (T4; 100 micrograms/kg per day for 7 days, i.m.) suppressed the GH responses to thyroidectomy. Bolus administration of T4 (10 micrograms/kg, i.m.) to thyroidectomized birds promptly lowered the circulating GH concentrations, which remained suppressed for at least 4 h. Chronic (daily injections for 7 days) or acute (one injection) pretreatment of thyroidectomized birds with iopanoic acid (IOP; 40 mg/bird, i.m.) before the bolus administration of T4 attenuated, but did not prevent, inhibition of circulating GH levels by T4. Administration of IOP (40 mg/bird i.m.) 24 h and immediately before the administration of tri-iodothyronine (T3; 3 micrograms/kg, i.m.) or T4 (10 micrograms/kg, i.m.) also failed to suppress thyroidal inhibition of circulating GH concentrations in thyroidectomized birds. Administration of IOP alone had no effect on GH concentrations. Circulating T3 concentrations were not enhanced following the administration of T4 to IOP-treated birds, indicating its inhibition of hepatic monodeiodinase activity. The metabolic clearance rate (MCR) of 125I-labelled chicken GH in the plasma of thyroidectomized fowl was less than that in sham thyroidectomized birds. Following pretreatment with T4 (100 micrograms/kg per day for 7 days) sham-thyroidectomized and thyroidectomized birds did not differ significantly in their MCR. The GH secretion rate in thyroidectomized birds was similar to that in sham-thyroidectomized birds and in both groups was markedly reduced following pretreatment with T4. These results demonstrate thyroidal inhibition of circulating GH concentrations in fowl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313217 TI - Maternal modulation of growth hormone secretion in the neonatal rat: involvement of mother-offspring interactions. AB - Serum GH levels increased in 2- or 8-day-old rat pups when sucking mammary glands whose main milk ducts were ligated. Although intragastric administration of rat milk has been shown to increase serum GH levels in neonatal rats, ingestion of milk during suckling did not increase serum GH values further. In another experiment, 2-day-old pups obtained no milk when they were suckled by anaesthetized mothers, and in this instance the serum GH concentration of the pups decreased. This decrease was prevented if the mothers were injected with oxytocin to counteract the depressant effect of the anaesthesia on milk ejection; nevertheless, GH levels in neonatal animals failed to increase following suckling. Thus some aspect of maternal activity appears to be involved in the suckling-induced increase of serum GH in rat pups. To elucidate which components of maternal activity might be involved, the effects of manipulations of ambient temperature as well as stimulation of the oral or anogenital regions were examined. Exposing rat pups to 37 degrees C (nest temperature) during the 6-h separation period before suckling prevented the separation-induced decrease in serum GH levels of 2-day-old pups. Moreover, exposure to 37 degrees C for 30 min following a 6-h separation at room temperature (22 degrees C) mimicked the effect of suckling in increasing serum GH levels in the pups. Suckling following separation at 37 degrees C was unable to increase serum GH values further.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313218 TI - Effect of ovariectomy and treatment with ovarian steroids on vasopressin release and fluid balance in the rat. AB - Plasma vasopressin concentrations have previously been shown to vary during the oestrous cycle of the rat, being highest on the morning of pro-oestrus and lowest on dioestrus day 1. To determine the effect of gonadal steroids on vasopressin secretion and fluid balance, mature rats were ovariectomized and given oestrogen, progesterone or vehicle alone s.c. for periods of up to 16 days. Plasma vasopressin concentrations fell after ovariectomy and this was reflected in an increase in 24-h urine volume. The normal increase in plasma vasopressin concentrations seen over day-light hours was also suppressed. The change in vasopressin concentrations observed on steroid treatment depended upon both the dose and the duration. High doses of oestrogen were associated with a fall in plasma vasopressin, probably as a result of fluid retention. Thus, of an initial group of rats given silicone elastomer implants containing 50, 500 or 1000 micrograms oestradiol in oil, plasma vasopressin concentrations were reduced after 7 days treatment with 1000 micrograms oestradiol implants in association with reduced plasma sodium concentrations. Daily s.c. injections of 100 micrograms oestradiol benzoate/100 g body weight produced an immediate small increase in plasma vasopressin concentrations, but by 14 days the plasma concentrations of 0.7 +/- 0.16 pmol/l (mean +/- S.E.M.) had fallen significantly and were less than those in the vehicle-treated group (1.2 +/- 0.26 pmol/l). However, after treatment for 14 days with implants containing only 50 micrograms oestradiol, plasma vasopressin concentrations were higher compared with the group receiving vehicle alone, despite the fact that the plasma osmolality was lower in the latter group, suggesting a long term resetting of the osmoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313219 TI - Measurement of parathyroid hormone-related protein in extracts of fetal parathyroid glands and placental membranes. AB - A radioimmunoassay based on an antiserum to human parathyroid hormone-related protein PTHrP(1-16) was used with PTHrP(1-34) standard to measure the concentration of immunoreactive PTHrP in extracts of fetal parathyroid glands from lambs and calves and also placental membranes obtained from several species, including man. Dilution curves from these sources were parallel to those obtained for PTHrP(1-34) standard. It was demonstrated that this parallelism was not the result of tracer damage caused by enzymic activity in the tissue extracts. Extracts of human placental membranes were subjected to high-pressure liquid chromatography with a linear acetonitrile gradient. Co-elution of cytochemical biological activity with 125I-labelled PTHrP(1-34) was noted. These results provide further evidence for both the fetal parathyroid glands and the placenta containing material resembling PTHrP which may be responsible for sustaining the activity of the placental calcium pump which maintains the fetus hypercalcaemic relative to its mother. PMID- 2313220 TI - Characterization of a tissue kallikrein in human prolactin-secreting adenomas. AB - Immunoreactive tissue kallikrein was co-localized with prolactin in all the eleven prolactin-secreting adenomas of the human anterior pituitary gland examined in this study. The intracellular distribution of immunoreactivity in the prolactin-secreting cells suggests that tissue kallikrein is located within the Golgi complex of these cells. Both the intracellular hormone-processing action and the kininogenase activity of tissue kallikrein may be of functional importance in human prolactinomas. PMID- 2313221 TI - Human 'pregnancy-associated endometrial alpha 1-globulin', a 32 kDa insulin-like growth factor-binding protein: immunohistological distribution and localization in the adult and fetus. AB - We have previously shown that pregnancy-associated alpha 1-globulin, a small molecular weight (32 kDa) insulin-like growth factor-binding protein (IGF-BP), is quantitatively the major secretory protein product of the decidualized endometrium during human pregnancy and is localized principally in the decidual cell. In the present study, employing monoclonal antibodies in immunohistological techniques, the distribution and localization of IGF-BP has been examined in normal and pathological tissues of the adult and first trimester fetus. In the adult, most intense reactivity was associated with endometrial stroma and their derived decidual cells in the uterus or in ectopic sites in patients with endometriosis. During the menstrual cycle, the appearance of IGF-BP in endometriotic tissue was linked with its appearance in uterine endometrial tissue. The only other adult cells where significant staining was detected was in the luteal cells of the corpus luteum. Production of the protein was not a feature of carcinomas. In the fetus, the protein was localized in lymphoid myeloid progenitor cells and hepatocytes of the liver and at lower levels in testicular Leydig cells and adenocortical cells. These observations suggest highly specific tissue expression of this protein and support a specialized role for this protein in progenitor cells of the lymphomyeloid system, in certain steroid hormone-producing cells and in the decidual cell in pregnancy. PMID- 2313222 TI - How should obesity be defined? PMID- 2313223 TI - Blood pressure response during maximal exercise in apparently healthy men and women. AB - The blood pressure (BP) response during a maximal ergometer bicycle test was studied in 190 apparently healthy subjects (95 men and 95 women) aged 21-70 years. The starting load was 50 W and was increased by 50 W every 4 min until exhaustion. Mean physical performance expressed as cumulative work was 2276 +/- 789 W in men and 1109 +/- 276 W in women (P less than 0.0001). The maximum heart rate was similar in men and women and declined significantly with age (r = -0.78, P less than 0.001 for men and r = -0.64, P less than 0.0001 for women). The mean maximal systolic blood pressure (MSBP) was 193 +/- 23 mmHg in men and 171 +/- 21 mmHg in women (P less than 0.0001). Men aged greater than or equal to 50 years had a MSBP of 201 +/- 22 mmHg, compared to 188 +/- 22 mmHg in those aged less than 50 years (P less than 0.01). Women aged greater than or equal to 60 years had a MSBP of 190 +/- 21 mmHg compared to 166 +/- 19 mmHg in their younger counterparts (P less than 0.001). The diastolic BP showed a similar modest increase at all ages and in both sexes. SBP is dependent on age and gender and this must be taken into consideration when assessing a normal response in individual patients. PMID- 2313224 TI - Right arm involvement and pain extension can help to differentiate coronary diseases from chest pain of other origin: a prospective emergency ward study of 278 consecutive patients admitted for chest pain. AB - In a prospective study of 278 consecutive patients admitted to an emergency ward for chest pain, the 115 clinical and paraclinical parameters available at the time of admission were evaluated by computer comparison with the final diagnoses. The most valuable items for making the diagnosis were classified according to their sensitivity, specificity and predictive value. Among the 278 patients, 100 individuals had myocardial infarctions (MI), 47 had unstable angina, 25 had stable angina and 106 patients had a non-coronary disease. The twelve most sensitive items for distinguishing MI from other conditions were the following: sudden onset of pain (70%); duration of more than 60 min (88%); constriction and squeezing (79%); oppression (75%); prior anginal attacks (61%); sex male (72%); age over 60 years (74%); abnormal heart auscultation (62%); abnormal electrocardiogram (ECG) (98%); segment (ST) disturbances (86%); increased glucose level (77%); CKMB fraction greater than 6% of total creatine kinase (CK) level (63%). Among the twelve most specific items, also with the best positive predictive value, irradiation in the right arm is of most importance; among the 51 patients with right arm involvement, 48 suffered from a coronary disease and 41 from a myocardial infarction. The largest extension of pain was reported in the latter group. It is concluded that chest pain with a wide irradiation involving the right arm strongly suggests that a myocardial infarction is ongoing. PMID- 2313225 TI - Influence of menopause on dietary treatment of obesity. AB - Obese women (n = 104) were treated with an energy reduced diet (1100 kcal d-1) in a strictly standardized outpatient regime. Body composition, regional adipose tissue distribution, regional fat cell sizes and metabolic variables were followed before treatment, after 5% weight loss and at the stage when there was no further weight loss. Premenopausal women lost less body fat and relapsed earlier after treatment, compared with menopausal women. Fat loss appeared to be more uniform, and included several adipose tissue regions in postmenopausal women, while younger women seemed to lose fat mainly from the epigastrial fat cells. Higher baseline levels of thyroid hormones were associated with increased fat loss and a tendency to lose less lean body mass. Waist/hip and waist/thigh ratios did not change in response to weight loss. The addition of fibre to the diet did not affect the rate of relapse. These results suggest that obesity treatment by implementation of a negative calorie balance might be more successful in postmenopausal than in younger women, perhaps due to the more uniform availability of body fat in the former. PMID- 2313226 TI - Low dose acetylsalicylic acid and thromboxane release at the site of plug formation in vivo in elderly patients with cardiovascular disease. AB - Thromboxane B2 (TXB2) levels in bleeding time blood and in serum were measured in 13 elderly patients with cardiovascular disease, seven of whom were receiving continuous treatment with low dose acetylsalicylic acid (ASA, 125 mg every second day--250 mg daily) for prevention of stroke. Blood sampling was performed openly, but assays of TXB2 were performed by a blinded investigator. In patients treated with ASA, median serum TXB2-levels were 4% and TXB2-levels in bleeding-time blood were less than 16% of the corresponding levels in patients without ASA (P less than 0.01). The results show that in elderly atherosclerotic patients very low doses of ASA substantially suppress TXB2 formation, not only in serum but also at the site of local haemostasis. The extent of suppression is comparable to that previously reported from young healthy subjects. PMID- 2313227 TI - Two-year survival after myocardial infarction. AB - We have studied 773 consecutive cases (706 individuals) with definite myocardial infarction treated in the Coronary Care Unit at Danderyd Hospital in Stockholm during the period 1984-85. Hospital mortality was 12.9% in all patients and 8.9% in patients under 70 years of age. Six hundred and six patients were discharged from the hospital and followed up for 2 years. The 2-year mortality in ischaemic heart disease was 14.4% in all patients and 9.5% in patients under 70 years of age and, including all causes of death, 20.3% and 14.6%, respectively. Our policy for medical treatment included frequent use of beta-adrenergic blocking agents, even in heart failure, and restricted use of antiarrhythmic drugs and digitalis. A short delay of admission may have been beneficial for the result of different kinds of anti-ischaemic intervention. Furthermore, a routinely performed exercise ECG before discharge and after 6 weeks, as part of a structured follow-up, has improved our ability to detect complications at an early stage and to optimize medical treatment. PMID- 2313228 TI - Increased turnover of very low density lipoprotein triglyceride during treatment with cholestyramine in familial hypercholesterolaemia. AB - Kinetics of very low density lipoprotein (VLDL) triglyceride were determined in seven patients with heterozygous familial hypercholesterolaemia, using a 3H glycerol technique. The study was repeated after 5-7 weeks of therapy with the bile acid-binding resin, cholestyramine. The rate of synthesis of VLDL triglyceride was increased by 85% (P less than 0.05) during resin therapy. Simultaneously, the fractional catabolic rate of VLDL was increased by 40% (P less than 0.02), so that only a moderate increase in plasma concentration was observed. Repeated measurements of VLDL size by electron microscopy (before, 1 week, and 5-7 weeks after initiation of therapy) indicated that a transient increase in VLDL size occurred in response to cholestyramine. The results are consistent with a stimulatory effect of bile acid sequestrants on VLDL triglyceride production and indicate that, in most subjects, a compensatory increase in VLDL triglyceride removal occurs. PMID- 2313229 TI - Self-terminating idiopathic ventricular fibrillation presenting as syncope: a 40 year follow-up report. AB - Out-of-hospital ventricular tachyarrhythmia has a high mortality. Most patients sustaining this type of arrhythmia have an organic heart disease. In this case report we present a patient with recurrent ventricular fibrillation with the clinical appearance of syncope, where no relevant organic heart disease could be found at autopsy performed 40 years later. PMID- 2313230 TI - Mediastinal tumour as the presenting manifestation of Wegener's granulomatosis. AB - A 42-year-old man presented with a mediastinal tumour. On histological examination, tuberculosis was evoked, but no definitive conclusion could be drawn. The patient thereafter developed throat ulcerations and rapidly progressing renal insufficiency due to necrotizing glomerulonephritis. After reviewing the histological material, it was concluded that all of these manifestations were related to Wegener's granulomatosis. The presentation of Wegener's granulomatosis as a mediastinal tumour is very rare, but this form of the disease must be recognized, as early treatment with cyclophosphamide is essential for a favourable outcome. PMID- 2313231 TI - Differential kinetics of glucose metabolism in porcine retinal and aortic endothelial cells. AB - Rates of glucose utilization, measured by steady state lactate production, and the rates of initial uptake of [14C]glucose were determined in cultured porcine retinal endothelial cells. The apparent Km for the steady state process proved to be lower than that determined for the uptake step (0.20 vs. 0.86 mmol/l glucose), suggesting that the carrier-mediated uptake of glucose into retinal endothelial cells cannot be the rate limiting step of overall glucose consumption. Thus, porcine retinal endothelial cells differ from porcine aortic endothelial cells, in that the aortic endothelial cell membrane acts as a barrier for the uptake of glucose into the cell. Accordingly, dexamethasone, which is known to reduce glucose uptake and degradation in aortic endothelial cells, does not influence glucose utilization in the retinal cells. PMID- 2313233 TI - Drug-induced decrease of serum alanine and aspartate aminotransferase activity in the rat, as a result of treatment with oxodipine, a new calcium channel blocker. AB - Chronic oral administration of oxodipine, a new calcium channel blocker, resulted in a reduction in the blood enzyme activity of alanine and aspartate aminotransferase. The reductions were both time and dose related. The decline in enzyme activities was accompanied by microscopic hepatic changes, which in the opinion of the authors should have been associated with an increase in the enzyme activities of alanine aminotransferase and aspartate aminotransferase. The effect was only partially reversed one month after the cessation of oxodipine treatment. PMID- 2313232 TI - Antibodies from colostrum in oral immunotherapy. AB - An immunoglobulin preparation for oral use was prepared from pooled bovine colostrum from more than 100 animals. The preparation has high antibacterial antibody titres, and a high capacity for the neutralization of bacterial toxins. It is well tolerated and highly effective in the treatment of severe diarrhoea, e.g. in AIDS patients. The preparation is spray-dried and stable at 2-8 degrees C. PMID- 2313234 TI - Tubule-derived membrane glycoproteins in the urine of patients (including those with AIDS) as analysed by radioimmunoblotting. AB - As a contribution to the noninvasive diagnosis of kidney damage, polyclonal antisera specifically directed against brush border surface glycoproteins of the proximal tubule of the human kidney were used in radioimmunoblotting studies for the assessment of kidney-tissue proteinuria. Urine specimens from healthy controls, from patients (n = 41) with various forms of renal involvement and from those suffering from symptomatic HIV-infection (AIDS) but having normal kidney function, were investigated for the excretion of kidney-derived membrane proteins. After SDS-polyacrylamide gel electrophoresis of urine samples and electroblotting of protein bands on nitrocellulose sheets, followed by incubation with the antibody and subsequently with 125I-labelled protein A, 3 major tubular glycoproteins (Mr 240 000, 160 000, 120 000) were revealed by autoradiography. The results indicate and increased shedding of epithelial membrane glycoproteins in the urine of patients with kidney lesions, and they also demonstrate the suitability of radioimmunoblotting for the determination of such tissue-antigens ("brush border-histuria"). PMID- 2313236 TI - Accuracy of serum ferritin determinations in tissue preparations and human serum. AB - Introduction of the NBSB 80/602 reference preparation for the calibration of ferritin immunoassays has reduced the inter-assay variability, and represents the first important step towards standardisation of ferritin immunoassays. However, our investigations show that comparison between assay results is still impossible, owing to differences in assay methodology and performance, differences in the specificities of the antibodies and antigens used and other possible interfering substances. We conclude that all kits detect mainly the more basic isoferritins in serum, and that all isoferritins (acidic, intermediate and basic) are systematically underestimated. Since we also showed possible immunological differences between reference or kit standards and serum ferritin, we conclude that the present kits have poor accuracy. To diminish inter-assay variability and to increase the accuracy of serum ferritin determinations, a method is needed that detects all basic, intermediate and acidic isoferritins and measures the true ferritin concentration in serum under normal and pathological circumstances. This reference method can be used to evaluate interference and systematic errors in routine methods. The introduction of a reference method, in combination with the NBSB 80/602 human liver reference preparation, is the second important step towards the accurate standardisation of ferritin immunoassays. PMID- 2313235 TI - Identification and quantification of Bence-Jones proteinuria by automated nephelometric screening. AB - A two-step screening of urine samples for Bence-Jones proteins is described. The proposed method is fast and fully mechanized; quantitative results are obtained within minutes. As a first step alpha 1-microglobulin, albumin, transferrin and IgG are measured immunonephelometrically. Then the cumulative concentration of the four markers is compared with that of total protein, which is determined by nephelometry during trichloroacetic acid protein precipitation. Bence-Jones proteinuria is indicated by large concentrational differences (greater than 31%) between the four markers and total protein. As a second step, Bence-Jones proteins are assessed directly if they are present. Immunoglobulin light-chains are measured immunonephelometrically and the kappa:lambda ratio is used to discriminate between monoclonal and polyclonal forms. Using this strategy, urine samples from 84 patients with monoclonal gammopathia or multiple myeloma were screened. Bence-Jones proteinuria was detected in 40 cases. In a reference collective (69 patients with different types of renal proteinuria) Bence-Jones proteinuria was not observed. Comparing the results with those obtained by immunofixation, the nephelometric method has a sensitivity of 100% and a specificity of 97%, differing only in a single false-positive result. Additional information about renal forms of proteinuria is supplied by the first screening step. This permits an assessment of the renal involvement in Bence-Jones proteinuria, and the method can also be used for nephrological diagnosis. PMID- 2313237 TI - Systematic studies on parameters influencing the performance of the polymerase chain reaction. AB - To obtain a detailed understanding of the various factors influencing the polymerase chain reaction, we optimized parameters such as ion concentration, pH, primer sequence and concentration, hybridization stringency, cycle numbers, etc. Using 3 different plasmids (2 HIV2 clones and pUC18) and several genomic DNA samples from HIV-positive patients as templates, together with 6 sets of primers, the following optimal conditions were found: the DNA should be linearized, the primer concentration should be 0.1-0.2 mumol/l, and the magnesium ion concentration should be less than 2 mmol/l. The pH of the reaction mixture should be 8.5-9.0. Twenty five cycles are sufficient. For fragments greater than 10(3) bases the elongation time should be 5 min. The elongation temperature is not critical and can vary between 50 and 70 degrees C. The hybridization temperature can be used to control the specificity of the polymerase chain reaction and, finally, mismatches at the 3' end of the primer can totally inhibit the amplification. PMID- 2313238 TI - Comparison of cyclosporin A measurement in whole blood by six different methods. AB - In a multicentre trial, we analyzed and compared the cyclosporin concentrations in whole blood specimens (trough values) from renal and bone marrow transplant patients using six different methods: high-performance liquid chromatography (n butyl reversed-phase column) as reference, and 5 immunoassay procedures using monoclonal specific or non-specific antibodies, or polyclonal antibodies, for measuring cyclosporin with and without its cross-reacting metabolites. Results obtained by the 2 specific RIAs show good correlations (r-values of 0.945 and 0.921) versus the HPLC method, with average assay ratios of: 1.52 for 3H-RIA/HPLC and 1.26 for 125I-RIA/HPLC. In contrast, ratios for non-specific immunoassay/HPLC show multiple-fold overestimations of cyclosporin with very wide variations: 4.58 for 3H-RIA/HPLC, 3.97 for 125I-RIA/HPLC and 3.87 for fluorescence polarization immunoassay (FPIA)/HPLC. These findings indicate 1) that the 'specific' 3H- and 125I-RIAs can be used for cyclosporin measurements in whole blood using normal therapeutic ranges established by HPLC, 2) that the important disparity and variable overestimations by 'non-specific' RIA or fluorescence polarization immunoassay, compared with HPLC, require adjustments in therapeutic ranges, and 3) that the available 'specific' and 'non-specific' immunoassays should enable establishment of within-house reference 'therapeutic/toxic' ranges for cyclosporin in individual centres, based on these 'specific' versus 'non specific' assays. PMID- 2313239 TI - Unexpected divergence among identified interneurons in different abdominal segments of the crayfish Procambarus clarkii. AB - The command elements that initiate and coordinate the abdominal movements in crayfish show little similarity between the various abdominal segments. Our criteria for similarity among interneurons were based on both cell morphology and electrophysiology. By contrast, previously published evidence shows much greater intersegmental similarity in the skeletal, muscular, motoneuronal, and sensory components of the abdominal system in crayfish, structures that are controlled by or send information to the command elements. Therefore, unlike the command elements, these structures have retained nearly identical form and function in the various segments. We also found in different ganglia examples of interneurons involved with abdominal positioning behavior that have similar morphology but different function and vice versa. Such interneurons could represent divergent pairs of serial homologues. It is unknown why so many of the abdominal positioning interneurons have become different. The various ganglia may perform subtly different functions, requiring differences in the positioning interneurons but not in the motor neurons or muscles. Alternatively, some of the abdominal positioning interneurons underlie more than one behavior; consequently, selection acting on these multiple functions may have changed these interneurons through evolution. PMID- 2313240 TI - Effect of sodium dodecyl sulfate on polar lobe formation and function in Ilyanassa obsoleta embryos. AB - Polar lobes, anucleate vegetal pole protrusions formed by Ilyanassa obsoleta embryos, serve as a mechanism for shunting morphogenetic determinants to one cell during the first two cleavages. Polar lobe material becomes segregated in the CD cell during first cleavage and in the D cell during second cleavage, resulting in a very unequal four-cell stage. Larval structures including external shell, foot, operculum, statocysts, and eyes develop only when polar lobe material is present. Treatment with the anionic detergent sodium dodecyl sulfate (SDS) before and during the first cleavage inhibited polar lobe formation and equalized cleavage, as the lobe material was distributed to two cells. No polar lobes formed during second clevage in SDS-equalized embryos, and the four-cell stage consisted of four equal cells with reduced cell contacts. SDS inrreversibly inhibited polar lobe formation without affecting cytokinesis. Although 27% of the larvae from SDS equalized embryos had one or more lobe-dependent structures duplicated, morphogenesis was impaired: more than 40% of such larvae failed to form shell and/or statocysts. When cells were separated after equalized first cleavage and raised as pairs, the pairs of resulting larvae duplicated lobe-dependent structures with the same frequency as whole equalized embryos. Possible explanations for impaired morphogenesis in SDS-treated embryos are discussed. PMID- 2313241 TI - Feminization of the hepatic microsomal cytochrome P-450 system in brook trout by estradiol, testosterone, and pituitary factors. AB - The effects of estradiol, testosterone, and pituitary extract on hepatic microsomal enzymes were studied in sham-operated and gonadectomized immature brook trout. Estradiol reduced the specific content of cytochromes P-450 and b5 by 70% or more in both groups. Testosterone and pituitary extract also decreased the levels of total P-450 and b5, but to a lesser extent. These latter effects were not evident when the contents of P-450 and b5 were normalized per g liver. Immunoblot analysis with antibodies to P-450 forms from a teleost (scup) showed the presence of cross-reacting proteins in control fish, presumed counterparts to the scup forms. Levels of a trout counterpart to P-450A (a putative testosterone 6 beta-hydroxylase) were strongly suppressed in estradiol-treated fish. A trout P 450B counterpart was suppressed in estradiol-treated fish, but less strongly than was the P-450A counterpart. The trout orthologue of hydrocarbon-inducible P-450E (P-450IA1), the aryl hydrocarbon hydroxylase (AHH) catalyst, was undetectable in any group, consistent with very low levels of AHH activity in these fish. Estradiol or pituitary extract also decreased the levels of NADH-cytochrome b5 and NADPH-cytochrome P-450 reductase activities in sham-operated but not in total P-450 or b5, suggesting an influence of gonads in maintaining normal levels of the reductases. The results support a prominent suppressive role for estrogens in producing the general sex differences in microsomal enzymes in fish liver and indicate that there could be affects on several P-450 forms. However, the mechanism of hormone action in this regulation is uncertain. The results also suggest the existence of unidentified, possibly gonadal, factors which contribute to the regulation of reductases in teleost liver. PMID- 2313244 TI - Effect of maternal age on the incidence of digynic triploidy in LT/Sv strain mice: implications for the ovulation of primary and secondary oocytes in this strain. AB - LT/Sv strain mice ovulate both primary and secondary oocytes, which are fertilisable, giving rise to digynic triploid and normal diploid fertilised conceptuses, respectively. Since the proportion of primary and secondary oocytes ovulated in our earlier studies varied widely among females, we investigated whether the proportion of primary oocytes ovulated in LT/Sv strain mice was influenced by maternal age. Females 6, 12, 18, 24, and 30 weeks old were mated with F1 hybrid males. The females were autopsied on the 10th day of gestation, and the intact conceptuses or extraembryonic membranes analysed cytogenetically. Since no selective loss of the triploids occurs up to the 10th day of gestation, analysis at this time also provides indirect information on the proportion of primary and secondary oocytes ovulated. We observed 1) that the overall incidence of triploidy decreased from 55% in the 6-week-old females to 6% in the 30-week old group; 2) that the number of females from which both triploid and diploid embryos were recovered decreased with increased maternal age; 3) that a substantial decrease in the proportion of triploid embryos was observed in those females in which both triploid and diploid embryos were recovered, in relation to increased maternal age; 4) that there was no overall decrease in the total number of implants with increasing age; and 5) that there was no increase in the incidence of resorptions with increasing maternal age. We believe that no comparable relationship between the ovulation of primary and secondary oocytes and maternal age has previously been reported. PMID- 2313242 TI - Germ cell deficiency causes testis cord differentiation in reconstituted mouse fetal ovaries. AB - Sex-reversal in fetal ovaries was studied by using a dissociation-reconstitution technique. Gonads of 12.5 gestation-day male and female mouse fetuses were dissociated into single cells. To eliminate germ cells, the dissociated cells were cultured for 14 h, and then somatic cells attached to culture dishes were harvested and aggregated by gyratory culture for 24 h. The aggregates were then transplanted into ovarian bursa in ovary-ectomized nude mice. The recovered explants were examined histologically. Male somatic cells developed into testes containing Sertoli cells, Leidig cells, and tunica albuginea. Female somatic cells formed testis cords and differentiated into Sertoli cells, but they did not differentiate into other testis components or ovarian tissues. However, aggregates consisting of both female and male somatic cells differentiated into well-developed testes containing Leidig cells and tunica albuginea as well as Sertoli cells. Enzyme marker analysis showed significant contributions of female cells in these organized testes. In contrast, aggregates containing both female germ cells and somatic cells developed into ovaries and did not differentiate into any testicular tissues. The results indicate that female somatic cells in fetal gonads at 12.5 gestation day have the potency to form testis cords and differentiate into Sertoli cells. The subsequent steps in testis development require the contributions of male cells. The present study also suggests that testicular differentiation is independent of germ cells but ovarian development involves the interaction between germ cells and somatic cells. PMID- 2313243 TI - Developmental change in follicular cell-enhanced amino acid uptake into mouse oocytes that depends on intact gap junctions and transport system Gly. AB - Uptake of L-alanine, L-lysine, and choline into both preantral and antral mouse oocytes was enhanced by follicular cells. Follicular cells also enhanced glycine uptake into oocytes at the preantral stage of development, but no effect of these cells was observed at the antral stage. Glycine uptake was predominantly Na+ dependent and inhibited almost completely by 10 mM sarcosine, moderately by proline and its analog pipecolate, and poorly or not at all by other amino acids. By these criteria, glycine transport was mainly via system Gly in follicular cells and the oolemma at both the preantral and antral stages. Moreover, an increase in glycine transport via the oolemma between the preantral and antral stages was more than threefold larger than was the increase in transport of alanine or lysine. This relatively large increase in glycine-specific transport in the oolemma appears to obscure the ability of follicular cells to enhance glycine uptake into antral oocytes. In contrast to other amino acids, leucine uptake into oocytes was not enhanced by follicular cells unless 14 other amino acids were also present at their concentrations in mouse serum. An inhibitor of gap junctional communication, 18-alpha-glycyrrhetinic acid, abolished follicular cell-enhanced uptake of glycine and choline into preantral oocytes. Therefore, the extent to which follicular cells enhance uptake of a particular amino acid into oocytes depends on at least three physiologically important variables. Namely, enhancement may depend on the stage of follicular development, the presence of other amino acids in the environment, and gap junctional communication. PMID- 2313246 TI - Effects of electric fields on fibroblast contractility and cytoskeleton. AB - We used silicone rubber substrata and fluorescent staining of cytoskeletal components to study the mechanisms by which electrical voltage gradients cause reorientation of embryonic chick fibroblasts in tissue culture. No evidence was found for a direct stimulation of cell contractility, either parallel or perpendicular to the voltage gradient. Instead, there was a gradual weakening in cell contractility in the axis parallel to this gradient, accompanied by progressive retraction of lamellae oriented along this axis, apparently due to selective weakening of cell-substratum adhesions. The cells then elongated perpendicular to the electric field, and strengthened their contractility in that axis. Fluorescence microscopy showed that cytoplasmic actin stress fibers and microtubules oriented perpendicular to the imposed voltage gradient. Many more cases were observed in which cell morphology had reoriented, but the actin fibers had not, as compared to the converse (cytoskeleton oriented, but no morphology). This disparity further supports the interpretation that the redirection of cell contractility is a consequence of morphological reorientation, rather than its cause. We also studied the effects of reversing the polarity of the electric fields at constant intervals (of as long as 1 minute). Fibroblasts failed to orient in response to such alternating fields, even after long exposure, but these same cells did reorient in response to pulsed currents in a consistent direction separated by "rest periods" (with no current). This combination of results is more consistent with an electrophoretic mechanism than with one depending on voltage-induced changes in membrane permeabilities. PMID- 2313245 TI - Phenotypic characterization of the transgenic mouse insertional mutation, legless. AB - In this report, we describe the dysmorphologic phenotype associated with the transgenic insertional mutation legless. This autosomal recessive, perinatally lethal mutation results in an interesting pleiotropic array of congenital malformations. The phenotype of the legless mutation in homozygous perinatal mutants is compared to wild-type nontransgenic and heterozygous siblings. Skeletal, craniofacial, and visceral malformations are characterized. We have observed by skeletal analysis a consistent loss of distal hindlimb structures, as well as the loss of distal forelimb structures with a predilection for the preaxial side of the developing forelimb. Craniofacial malformations commonly observed appear to represent a range of severity of affect, with the mildest manifestation evident as apparently shallow lateral clefts of the upper lip and mild midfacial clefts accompanied by clefts of the secondary palate. At the severe end of the spectrum, the midline clefts of the face (and secondary palate) are very wide, with obvious accompanying frontonasal encephaloceles and overt lateral clefts of the upper lip. Examination of the mutant brain has demonstrated marked defects in the anterior structures, particularly the olfactory lobes and cerebrum, in greater than 90% of the brains studied. Observation of the internal viscera has identified transposition of thoracic and abdominal organs in approximately 50% of the mutant offspring. The limb, head, and visceral defects were not observed in the wild-type nontransgenic or heterozygous siblings. Transgenic insertional mutations leading to congenital malformations are useful because the transgene sequence may serve as a tag to facilitate molecular retrieval. Analysis of the flanking DNA sequences will allow the identification of the interrupted gene. A complete description of the mutant phenotype will assist in the understanding of this genetic locus. PMID- 2313247 TI - Botryllus schlosseri (Tunicata) whole colony irradiation: do senescent zooid resorption and immunological resorption involve similar recognition events? AB - The colonial tunicate Botryllus schlosseri undergoes cyclic blastogenesis where feeding zooids are senescened and resorbed and a new generation of zooids takes over the colony. When non-identical colonies come into direct contact, they either reject each other or fuse. Fusion is usually followed by the resorption of one of the partners in the chimera (immunological resorption). The striking morphological similarities between the two resorption phenomena suggest that both may involve tissue destruction following self-nonself recognition events. Here we attempt to modify these two events by whole colony gamma irradiation assays. Three sets of experiments were performed: 1) different doses of whole colony irradiation for determination of irradiation effects (110 colonies, up to 8,000 rads); 2) pairs of irradiated-nonirradiated isografts of clonal replicates for the potential of reconstruction of the irradiated partners (23 pairs); 3) chimeras of irradiated-nonirradiated partners for analysis of resorption hierarchy. Mortality increased with the irradiation dose. All colonies exposed to more than 5,000 rads died within 19 days, while no colony died below 2,000 rads. The average mortality periods, in days, for doses of 6,000-8,000, 5,000, and 2,500-4,000 rads were 14.4 +/- 3.1 (n = 24), 19.8 +/- 6.0 (n = 15), and 19.6 + 5.1 (n = 22), respectively. Younger colonies (3-6 months old) may survive radiation better than older ones (more than 13 months). Many morphological alterations were recorded in irradiated colonies: ampullar contraction and/or dilation, accumulation of pigment cells within ampullae, abnormal bleeding from blood vessels, sluggish blood circulation, necrotic zones, reduction in bud number, and irregularities in zooid and system structures. With doses of 3,000 4,000 rads and above, irradiation arrested the formation of new buds and interrupted normal takeover, turning the colony into a chaotic bulk of vessels, buds, and zooid segments. Death supervened after a period of up to 1 month of poor condition, which was also characterized by loss of organization in systems. In isografts of irradiated-nonirradiated parts, the normal subclone resorbed all zooids and buds of the irradiated one within less than 1 week, even if it was up to 13 times smaller, without showing any sign of harmful effects. Thus, the irradiated subclone is not reconstituted by sharing blood circulation with a syngeneic part. Under 2,000 rads some of the irradiated zooids within this type of union started to regenerate, and at 1,000 rads no resorption was recorded, even though the number of zooids decreased in the irradiated part.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313248 TI - Characterization of membrane-associated actin in boar spermatozoa. AB - Biochemical, immunological, and electron microscopic methods have been used to provide semi-quantitative estimates and to localize actin in membranes of boar spermatozoa. Immunoblots, using a monoclonal antibody raised against actin from chicken gizzard, detected the protein in caput and cauda sperm plasma membranes. Immunoassay indicated that approximately 1% of the total plasma membrane protein was actin. Monomeric actin accounted for more than one-half of the membrane actin. Approximately 30-40% of plasma membrane actin was insoluble in Triton X 100, and approximately 10% of the total actin remained insoluble after treatment with guanidine hydrochloride. The presence of F-actin in sperm plasma membranes and in plasma membrane detergent-insoluble proteins was detected by fluorescence microscopy using the specific probe NBD phallacidin. When S1 myosin subfragments attached to colloidal gold were used to localize F-actin by electron microscopy, the label was restricted to the outer acrosomal membrane of intact epididymal and ejaculated sperm. Filaments appeared in short arrays along the anterior region of the membrane. S1/gold labeled detergent-insoluble plasma membrane fractions but did not label the plasma membrane in intact sperm. Filaments were least prominent in intact caput spermatozoa and most prominent in ejaculated spermatozoa. We conclude that most actin associated with sperm membranes is in monomeric form in boar spermatozoa, but that actin filaments or protofilaments are components of the outer acrosomal membrane. These filaments may also associate with the plasma membrane overlying the acrosome. PMID- 2313250 TI - "Observations and statistics relating to suicide weapons": an update. PMID- 2313249 TI - Glycine protects preimplantation mouse conceptuses from a detrimental effect on development of the inorganic ions in oviductal fluid. AB - Two-cell mouse conceptuses were cultured in media that contained various concentrations of inorganic ions and amino acids. Substrates of the amino acid transport system Gly were detrimental to development at slightly hyposmotic concentrations of other ions. In contrast, these amino acids increased the frequency at which two-cell conceptuses developed into blastocysts at total ion concentrations of 355 to 405 mM. Data reported elsewhere is consistent with the possibility that the total ion concentration in oviductal fluid exceeds 360 mM, whereas the concentration of glycine in this fluid may be on the order of 10 mM. Therefore, a high ion concentration and glycine may counteract the potentially harmful effects of each other in situ. Like some marine organisms, preimplantation mouse conceptuses may use glycine as an intracellular osmolite because accumulation of inorganic ions could perturb the activities of some enzymes. PMID- 2313251 TI - Time since death and decomposition of the human body: variables and observations in case and experimental field studies. AB - Much of the difficulty in determining the time since death stems from the lack of systematic observation and research on the decomposition rate of the human body. Continuing studies conducted at the University of Tennessee, Knoxville, provide useful information on the impact of carrion insect activity, ambient temperature, rainfall, clothing, burial and depth, carnivores, bodily trauma, body weight, and the surface with which the body is in contact. This paper reports findings and observations accumulated during eight years of research and case studies that may clarify some of the questions concerning bodily decay. PMID- 2313253 TI - Metal mesh gloves for autopsy use. PMID- 2313252 TI - Opiate analysis in cadaveric blowfly larvae as an indicator of narcotic intoxication. AB - Specimens of liver were collected from 40 cases in which the cause of death had been determined to be opiate intoxication. Rearings of Calliphora vicina larvae were then promoted on the decomposing liver. A control group of 10 decomposed liver specimens from non-opiate deaths was treated similarly. Analysis of larvae and liver for opiates (morphine) was conducted by radioimmunoassay. Good qualitative and quantitative correlation was observed in both the positive and negative groups. Regression analysis comparing the concentrations of opiates found in the larvae with those found in the liver in the positive group resulted in a correlation of r = 0.790. PMID- 2313254 TI - Families, murder, and insanity: a psychiatric review of paternal neonaticide. AB - Neonaticide is the killing of a newborn within the first 24 h of life. Although relatively uncommon, numerous cases of maternal neonaticide have been reported. To date, only two cases of paternal neonaticide have appeared in the literature. The authors review neonaticide and present two new case reports of paternal neonaticide. A psychodynamic explanation of paternal neonaticide is formulated. A new definition for neonaticide, more consistent with biological and psychological determinants, is suggested. PMID- 2313255 TI - Female sex offenders: severe victims and victimizers. AB - Although there is an extensive body of literature concerning male sexual offenders, there is a marked lack of articles describing sexual offenses committed by females. The authors present a review of the existing literature on this topic and describe five cases of female sexual offenders and four cases of female sexual abusers. Implications for the effective assessment and treatment of this unique population are discussed. PMID- 2313256 TI - The accuracy of blood alcohol analysis using headspace gas chromatography when performed on clotted samples. AB - Subjects consumed alcoholic beverages and attained blood ethyl alcohol concentrations ranging from 0.02 to 0.15 g/dL. Sets of blood samples were drawn from these subjects, including some samples that were allowed to clot and some in which anticoagulent was added. A quantitative analysis for ethyl alcohol was performed on these samples using headspace gas chromatography. The mean deviation of the concentration of ethyl alcohol in the clotted samples from the ethyl alcohol concentration in the corresponding control samples was 0.001 g/dL. The 99% confidence interval for this mean was +/- 0.0005 g/dL. PMID- 2313257 TI - Gm/Km typing of bloodstains in U-bottom microtiter plates. AB - A technique was developed for Gm/Km typing of bloodstains and sera in U-bottom microtiter plates. Gm/Km typing of sweat and urine samples was also attempted with limited success. PMID- 2313258 TI - An improved method for complement subcomponent C1R typing. AB - An improved method has been developed for the reliable classification of different C1R genetic variant forms from human serum or plasma. The method combines the use of neuraminidase-digested samples followed by monodimensional isoelectric focusing in the pH range 5 to 8 followed by immunoblotting. The method yields a simple pattern, with one major band in homozygote and two major bands in heterozygote cases. PMID- 2313259 TI - Death following accidental sodium azide ingestion. AB - Two college students developed symptoms of poisoning following ingestion of a salt solution during a college physiology laboratory exercise. Symptoms included nausea, vomiting, diarrhea, and altered consciousness. The ingested solution was identified as isotonic buffered saline containing sodium azide in a concentration of 1.0 g/L. The solution was commercially prepared for instrumentation use only and was used inadvertently for the exercise instead of freshly preparing sodium chloride in water. One student drank three sips of the solution and survived. The other student drank 700 to 800 mL and over several days became progressively ill, suffering myocardial damage and cardiac dysrhythmias, and, finally, died. Toxicologic studies confirmed the presence of azide in an antemortem urine sample from the deceased. Sodium azide is an uncommon but potent poison which can cause serious illness and death. PMID- 2313260 TI - Fatal recreational inhalation of enflurane. AB - We report here a case of fatal enflurane poisoning by recreational inhalation, apparently the first published report of such a case. PMID- 2313262 TI - Analysis of gunshot residue test results in 112 suicides. AB - The results of gunshot residue (GSR) tests in 112 suicide cases investigated by the U.S. Army Criminal Investigation Command over a ten-year period are described. Only suicide cases in which there was certainty that the victim fired a weapon were examined in an effort to reduce ambiguous results. Previous case work research by Rudzitis indicated that positive GSR test results were encountered in suicides 62% of the time using various combinations of neutron activation analysis (NAA) and atomic absorption spectrophotometry (AAS). Threshold values of 0.2-micrograms antimony and 0.3-micrograms barium (0.2 micrograms antimony and 0.5-micrograms barium after 1985) used by the U.S. Army Criminal Investigation Laboratory resulted in positive GSR results in suicide cases 38% of the time. The effects of time, location of body, handling of the body, weapon type, caliber, and condition of the hands on GSR results are examined. Case studies involving suicides by unit armorers are discussed. PMID- 2313261 TI - Fly larvae: a new toxicological method of investigation in forensic medicine. AB - Toxicological analyses on a putrefied cadaver are sometimes difficult to achieve because of the absence of blood and urine. In this study, maggots, living material, are proposed as a new medium of investigation in forensic medicine. Five drugs (triazolam, oxazepam, phenobarbital, alimemazine, and clomipramine) were identified and assayed in some tissues of a putrefied cadaver and in the maggots found on and in the body. PMID- 2313263 TI - Examination and analysis of seat belt loading marks. AB - In moderate to severe collisions, large decelerations and hence large forces are generated. Various components of the seat belt system are loaded, and physical evidence of this loading may be observed long after the collision event. Such witness marks result from interaction between different components of the restraint system, or between the restraint and portions of the vehicle interior. Detailed examination and analysis of such marks can establish whether or not the seat belt was in use, and also the precise manner in which the seat belt was worn. Such investigative techniques are critical for evaluating the collision performance of occupant restraint systems, and for positively identifying cases of restraint system misuse. This paper reviews the types of physical evidence which may be observed to determine restraint usage. PMID- 2313264 TI - Thiamylal: review of the literature and report of a suicide. AB - A 28-year-old white male medical student was found hanging by the neck from the bathroom closet of a hotel room. An intravenous infusion line leading from a bottle of thiamylal sodium (an ultrashort-acting barbiturate) was inserted into the antecubital vein of the left arm. Blood was analyzed for alcohol and other volatiles and for acidic, basic, and neutral drugs. Only thiamylal was detected. Thiamylal was quantified by high-performance liquid chromatography with ultraviolet detection, and its presence was confirmed by gas chromatography/mass spectrometry. The tissue distribution of thiamylal was 29 mg/L in blood, 1.4 mg/L in urine, 16 mg/L in bile, 135 mg/kg in liver, 25 mg/kg in kidney, and 0.4 mg in the stomach contents. The uptake and distribution of thiamylal is similar to thiopental. The distribution of the drug in this case was compared to that of other fatalities involving ultrashort-acting barbiturates. PMID- 2313265 TI - Comparison of fingernail ridge patterns of monozygotic twins. AB - The ridge patterns on the fingernails of corresponding fingers of a pair of twins were compared microscopically and found to be readily distinguishable from one another. Based on blood grouping in six blood group systems (ABO, Rhesus, Ss, Duffy, Kidd, and Kell), the probability that the twins were monozygotic was calculated to be 89.1%. PMID- 2313266 TI - Immunoaffinity purification and characterization of the envelope protein E1 of hog cholera virus. AB - The envelope protein E1 of hog cholera virus (HCV) was isolated by immunoaffinity purification with monoclonal antibodies (MAbs) directed against HCV. E1 consisted of a doublet of glycoproteins which varied in size from 51K to 56K between the three strains tested. E1 contains major antigenic determinants of HCV which are conserved, and are involved in neutralization by MAbs. In infected cells, E1 was found always connected with a glycoprotein of 31K. When N-linked glycans were removed, E1 had a polypeptide backbone of approximately 47K. After proteolytic cleavage of E1 with Staphylococcus protease V8 and after electrophoresis and electrotransfer, peptide fragments containing different antigenic domains of E1 were detected with MAbs directed against HCV. PMID- 2313267 TI - The structural proteins of a porcine paramyxovirus (LPMV). AB - The porcine paramyxovirus is a newly identified agent of a fatal disease in piglets, endemic in Mexico since 1980, where it was seen around the town of La Piedad, Michoacan, Mexico (hence LPM virus). At least six [35S]methionine labelled proteins could be resolved by SDS-PAGE and five of them were clearly immunoprecipitated. Selective labelling of LPMV-infected cells with [3H]glucosamine revealed two bands with an Mr of about 66K and 59K, corresponding to the two viral glycoproteins, the haemagglutinin-neuraminidase protein and the fusion protein. Labelling of virus with [32P]orthophosphate disclosed one band with an Mr of 52K, corresponding to the phosphoprotein. Analysis of nucleocapsids obtained from purified virus or from a permanently infected cell line revealed one major band with an Mr of 68K, the nucleoprotein. Two other proteins were also identified, the large protein and the matrix protein, with apparent Mr of about 200K and 40K, respectively. The protein migration pattern of LPMV was compared, by SDS-PAGE, with that of Newcastle disease virus, bovine parainfluenza 3 virus and Sendai virus. Differences in the Mr of LPMV proteins and the proteins of these paramyxoviruses were observed. We propose that LPMV should be classified as a novel member of the genus Paramyxovirus. PMID- 2313268 TI - In vitro transcription of the double-stranded RNA genome of maize rough dwarf virus (Reoviridae). AB - An RNA-dependent RNA polymerase associated with particles of maize rough dwarf virus, a Fijivirus, was characterized using two in vitro assays differing in their energy regeneration systems. Optimum reaction rates occurred at pH 8.0 to 8.5 at 20 degrees C. The presence of virus and Mn2+ or Mg2+ was essential for enzyme activity; Mn2+ stimulated more incorporation events than Mg2+, at optimum concentrations of 2 to 4 mM and 4 mM, respectively. Incorporation was not affected by alpha-amanitin, actinomycin D or rifampicin. The products synthesized in vitro were single-stranded RNAs which hybridized specifically with the double stranded genomic RNAs of five other reoviruses. The in vitro transcripts were also used to detect maize rough dwarf virus RNA in plants and in vector insects. PMID- 2313270 TI - Sequence analysis and product assignment of segment 7 of the rice dwarf virus genome. AB - The complete nucleotide sequence of segment 7 of the rice dwarf virus (RDV) genome was determined. The segment was 1696 bp long and its plus-strand terminal sequence, 5'GGCAAA---UGAU3', was in agreement with the consensus sequence previously found in other segments of RDV. A 10 bp inverted repeat was found adjacent to the termini. A single long open reading frame extended for 1518 bp from the first AUG triplet (positions 26 to 28), and encoded a polypeptide of 506 amino acids (Mr 55,339). This protein had 32% identity in the amino acid sequence to the 57K protein encoded by segment 7 of the wound tumour virus genome. The translation product of transcript RNA made from 'tailored' cDNA of RDV segment 7 comigrated with the 60K core protein of RDV in 10% polyacrylamide gel and reacted with antiserum against the 60K core protein of RDV. Segment 7 of the RDV genome therefore codes for the 60K core protein. PMID- 2313269 TI - Nucleotide sequences of an Australian and a Canadian isolate of potato leafroll luteovirus and their relationships with two European isolates. AB - The genomes of an Australian and a Canadian isolate of potato leafroll virus have been cloned and sequenced. The sequences of both isolates are similar (about 93%), but the Canadian isolate (PLRV-C) is more closely related (about 98% identity) to a Scottish (PLRV-S) and a Dutch isolate (PLRV-N) than to the Australian isolate (PLRV-A). The 5'-terminal 18 nucleotide residues of PLRV-C, PLRV-A, PLRV-N and beet western yellows virus have 17 residues in common. In contrast, PLRV-S shows no obvious similarity in this region. PLRV-A and PLRV-C genomic sequences have localized regions of marked diversity, in particular a 600 nucleotide residue sequence in the polymerase gene. These data provide a world wide perspective on the molecular biology of PLRV strains and their comparison with other luteoviruses and related RNA plant viruses suggests that there are two major subgroups in the plant luteoviruses. PMID- 2313272 TI - Hepatitis B vaccine in the prevention of perinatally transmitted hepatitis B virus infection: final report on a West Midlands pilot study. AB - A four-dose vaccination schedule was used to interrupt perinatal transmission of hepatitis B virus from carrier mothers to their babies. Of 49 babies immunised and successfully followed up, 43 (88%) became immune: 15 out of 21 (71%) of babies born to HBeAg + mothers became immune, the other 6 becoming the only carrier babies in the study. Without immunisation a carrier rate in excess of 70% would have been expected in this high-risk group. Vaccine alone, given in a rapid immunisation schedule, protected the majority of babies at risk. In those babies in whom the carrier state occurred in spite of immunisation, infection may have taken place in utero, or the infant may have failed to produce adequate antibody in response to the vaccine. PMID- 2313271 TI - The absence of hepatitis B virus DNA in hepatitis B e antigen positive sera from chronic hepatitis B surface antigen carriers in China. AB - Sera from 20 Chinese patients with chronic hepatitis B were examined for hepatitis B e antigen and hepatitis B virus (HBV) DNA. There was considerable discordance with HBV DNA not being detectable in 10 out of 13 (77%) patients who were hepatitis B e antigen positive. Further testing for anti-HBe and HBV-DNA polymerase activity confirmed the results. Possible reasons for this discordance are discussed but neither hepatitis D (delta) infection nor the acquired immunodeficiency syndrome (AIDS) could be implicated. PMID- 2313273 TI - Inhibition of hepatitis B virus DNA polymerase by 3'-fluorothymidine triphosphate and other modified nucleoside triphosphate analogs. AB - The 3'-fluoromodified nucleotide analogs 3'-fluorothymidine triphosphate (FdTTP), 2',3'-dideoxy-3'-fluoro-5-chlorouridine triphosphate (F-5CldUTP), 2',3'-dideoxy 3'-fluoro-5-ethyluridine triphosphate (F-5EtdUTP), 2',3'-dideoxy-3'-fluorouridine triphosphate (FdUTP), and 2',3'-dideoxy-3'-fluoro-5-fluorouridine triphosphate (F 5FdUTP) as well as 2',3'-dideoxythymidine triphosphate (ddTTP), 2',3'-didehydro 2',3'-dideoxythymidine triphosphate (ddeTTP), 3'-chlorothymidine triphosphate (CldTTP), and 3'-rhodanothymidine triphosphate (SCNdTTP) were tested for their ability to inhibit hepatitis B virus (HBV)-associated DNA polymerase activity in vitro. The ID50 values of the most potent inhibitors were 0.15 microM for FdTTP, 0.2 microM for ddeTTP, 0.45 microM for ddTTP, and 0.8 microM for F-5CldUTP. SCNdTTP, CldTTP, and F-5EtdUTP were less efficient (ID50 = 3-5 microM), and FdUTP and F-5FdUTP were the least efficient inhibitors (ID50 = 25 microM) of the enzyme activity. Kinetic analysis revealed a competitive type of inhibition for FdTTP and ddeTTP. The Ki values were estimated to be 0.04 microM and 0.08 microM, respectively, compared with a Km value for dTTP of about 0.18 microM. PMID- 2313274 TI - Anti-PreS2 antibody assay for evaluating immune responses among recipients of recombinant hepatitis B PreS2 + S vaccine. AB - A competitive radioimmunoassay was developed for measuring hepatitis B virus (HBV) anti-PreS2 antibody. The assay has been demonstrated to be highly specific for anti-PreS2 antibody and not subject to interference by other antibodies to HBV-specific antigens. This assay was used to evaluate anti-PreS2 antibody responses in a hepatitis B PreS2 + S vaccine human clinical trial in healthy adults. PMID- 2313275 TI - Serum IgG subclass responses of humans to inactivated and live influenza A vaccines compared to natural infections with influenza A. AB - Studies with various viral agents have suggested that a preferential production of IgG subclasses may occur during infection, but limited information has been reported on the IgG isotypes produced during vaccination with live or killed virus preparations. The serum IgG subclass responses to influenza A infection or inoculation with live or killed influenza A vaccines were examined by an enzyme linked immunosorbent assay, and results were expressed using a 4-parameter logistic model. It was observed that IgG1 was induced by both natural infections and the live virus vaccine depending on the dose given. Inactivated vaccines induced significant titres of IgG1, IgG2, and IgG3 isotypes in vaccinees, again depending upon the amount of virus preparation administered. PMID- 2313276 TI - Danger at the waterhole. AB - The effects of declining accessibility of water and risk of electric shock on drinking patterns in rats were examined. Rats chose between two conditions to obtain their daily intake of water. In one condition, accessibility of water decreased systematically. In the other condition, water was readily accessible, but responses occasionally were followed by electric shock. Both variables affected drinking patterns similarly. As accessibility to water decreased, the number of drinking bouts initiated decreased but the quantity of water consumed increased. In response to risk of electric shock, the number of drinking bouts decreased but bout size increased. Results are considered in light of findings by Fanselow, Lester, and Helmstetter, (1988), Collier, Hirsch, and Hamlin (1972), and Marwine and Collier (1979). PMID- 2313277 TI - Recognition of altered shapes by hearing and hearing-impaired subjects. AB - In the present study, we explored whether mental transformation or feature detection is involved in visual processing of shape recognition; another purpose was to compare the visual processing of hearing subjects with that of hearing impaired subjects. Deprivation of hearing, according to Myklebust (1964), impedes perceptual functioning in some respects and enhances such functioning in other respects. An experiment was conducted using two-dimensional random shapes under similarity transformations in Euclidean space. Reaction time served as the behavioral measure. The analysis of variance results showed significant main effects of orientations, isometries, and shapes, but not of groups and sizes. There were significant linear trends for orientations and sizes. Both groups demonstrated mental isometric transformation. PMID- 2313278 TI - Illusion reversal rate as a function of subjective depth. AB - Undergraduate students (N = 48) served as subjects in a test of Gregory's theory of illusions. Twenty-four students made judgments about the subjective depth of three reversible illusions--Necker cube, Book, and Pyramid--under the conditions of complete versus incomplete illusions and illusions without depth cues versus with depth cues. An additional 24 subjects recorded the three illusion reversal rates under slightly altered conditions. Differences were found among the various illusions with respect to complete versus incomplete illusions, reversal rate, subjective judgments of depth, and certain correlation values. Support for Gregory's theory of illusion as displaced or misleading depth perception is offered by these results. PMID- 2313279 TI - Form characteristics of category-retrieval relationships in children and adults. AB - Subjects from Grades 2, 4, 6, and college performed a sort-recall task with 24 noncategorized items, using two 12-item sorts, four 6-item sorts, or six 4-item sorts. Among the children, the effects of increasing unitization at study were uneven across the category size conditions used and did not resemble the linear patterns shown by adults. Second graders showed retrieval advantages only for the smallest categories used, whereas fourth and sixth graders benefited from the use of moderately sized sorting categories but failed to show additional improvements for smaller sorting categories. An examination of subjects' sorting explanations suggested that different category-retrieval patterns may reflect better and poorer item relations established in smaller and larger categories, respectively. Sort conditions affording the best recall at the different grade levels were those in which subjects established the greatest number of contextual and categorical (taxonomic) relations among sorted items. PMID- 2313280 TI - Disordered children's acknowledgment of multiple emotions. AB - Two groups of normal and disordered children (6 to 7 years old and 10 to 11 years old) were presented with stories that could evoke the simultaneous experience of two different emotional impulses, especially when the two emotions were contrary in nature. Acknowledgment of the multiple emotional character of the situations occurred with the same frequency among normal and disordered children, but the disordered children more often denied all emotions or claimed that all negative emotions were applicable to the stories that contained two negative impulses. Disordered children also ascribed a higher intensity to acknowledged emotions than did normal children. It is argued that the acknowledgment of emotions is experienced as threatening by disordered children, which prevents them from analyzing the situation as thoroughly as normal children would. PMID- 2313281 TI - The effects of mellow and frenetic music on reported cognitions resulting from auditory subliminal messages. AB - Building on the work of Henley and Dixon (1974) and Mykel and Daves (1979), we investigated the effects of mellow and frenetic music on reported cognitions resulting from auditory subliminal stimuli. College students (N = 120) were randomly assembled into six groups. One third of the students heard four subliminally transmitted water-related words, one third heard four subliminally transmitted family-related words, and one third heard no subliminal stimuli. Either mellow or frenetic masking music was played for half the students in each group. Students reported more word-related imagery in the mellow music conditions than in the frenetic conditions, although the reported imagery did not correspond with the subliminal messages presented. PMID- 2313282 TI - A test for order relevance in a three-element serial learning task. AB - Rats were trained in a straight runway on a simple three-element series of differing reward quantities. The first trial of the series ended with a two pellet reward, and the second and third trials ended with a 12-pellet reward and a nonreward, respectively (2-12-0). All animals developed accurate anticipation of the terminal nonreward in the 2-12-0 series before it was rearranged for two test days during which the elements appeared in the order 12-2-0. The rats' anticipation of the terminal nonreward did not transfer to the reordered series, a result taken to mean that anticipation had been based upon interitem associations among memorial representations of the differing reward quantities. A second transfer test to 0-0-0, given after anticipation was reestablished to the 2-12-0 series, gave evidence that the ordinal position of the series elements was also a source of anticipation; the animals continued to run relatively slowly on the third trial in extinction. In neither transfer test was there evidence that the rats employed the strategy of enumerating rewarded trials, because counting is an order-irrelevant process. PMID- 2313283 TI - Effects of ratio reinforcement schedules on choice behavior. AB - Choice behavior under a concurrent VR-FR schedule of reinforcement was investigated in two experiments to test a molar theory of maximization. Hunger motivated albino rats pressed two bars, one on an FR10 and the other on a VR10 schedule, for a food reward. With the total number of experiences with each bar equated and interalternative switching eliminated during training, the study showed that during the choice test, the animals made significantly more responses to the VR than to the FR alternative, allocating about 75% of their responses to the VR alternative. The results suggest that, given an equal return of reward in the long run, the animals preferred a variable to a constant alternative in a choice situation. The findings are discussed in terms of a molar theory of maximization and a schedule-appropriate behavior interpretation of choice. PMID- 2313284 TI - Uptake of glycine into synaptic vesicles isolated from rat spinal cord. AB - Glycine was taken up by a synaptic vesicle fraction from spinal cord in a Mg-ATP dependent manner. The accumulation of glycine was inhibited by carbonyl cyanide-m chlorophenylhydrazone (CCCP) and nigericin, agents known to destroy the proton gradient across the vesicle membrane. Vesicular uptake of glycine was clearly different from synaptosomal uptake, with respect to both the affinity constant and the effect of Na+, ATP, CCCP, and temperature. Oligomycin and strychnine did not inhibit the vesicular uptake, showing that neither mitochondrial H(+)-ATPase nor binding to strychnine-sensitive glycine receptors was involved. It is suggested that the vesicular uptake of glycine is driven by a proton gradient generated by a Mg2(+)-ATPase. A low concentration of Cl- had little effect on the uptake of glycine, whereas the uptake of glutamate in the same experiment was highly stimulated. High concentrations of gamma-amino-n-butyric acid and beta alanine inhibited vesicular glycine uptake, but glutamate did not. Accumulation of glycine was found to be fourfold higher in a spinal cord synaptic vesicle fraction than in a vesicle fraction from cerebral cortex. PMID- 2313285 TI - In vivo measurements of ethanol concentration in rabbit brain by 1H magnetic resonance spectroscopy. AB - In vivo 1H magnetic resonance spectroscopy was used to measure the cerebral ethanol concentration in the rabbit after both intraarterial and intragastric administration. There was good agreement between cerebral and blood ethanol concentrations at all times after administration by either route. Cerebral ethanol levels, measured using in vivo 1H spectroscopy, agreed well with those measured in perchloric acid extracts of brain, analyzed by both high-resolution 1H spectroscopy and gas chromatography. Ethanol may be useful as an indicator to measure cerebral blood flow by 1H spectroscopy and chemical shift-selective magnetic resonance imaging. PMID- 2313286 TI - Acid homeostasis following partial ischemia in neonatal brain measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy. AB - The purpose of this study was to investigate neonatal brain energy metabolism, acid, and lactate homeostasis in the period immediately following partial ischemia. Changes in brain buffering capacity were quantified by measuring mean intracellular brain pH, calculated from the chemical shift of Pi, in response to identical episodes of hypercarbia before and after ischemia. In addition, the relationship between brain buffer base deficit and intracellular pH was compared during and following ischemia. Thus, in vivo 31P and 1H nuclear magnetic resonance spectra were obtained from the brains of seven newborn piglets exposed to sequential episodes of hypercarbia, partial ischemia, and a second episode of hypercarbia in the postischemic recovery period. For the first episode of hypercarbia, brain buffering was similar to values reported for adult animals of other species (percentage pH regulation = 54 +/- 16%). During ischemia, the brain base deficit per unit change in pH was -19 +/- 5 mM/pH unit, which is similar to values reported for adult rats. By 20-35 min postischemia, brain acidosis partly resolved in spite of a net increase in lactate concentration. Therefore, the consumption of lactate could not explain acid homeostasis in the first 35 min following ischemia. We conclude that H+/HCO3- or other proton equivalent translocation mechanisms must be sufficiently developed in piglet brain to support acid regulation. This is surprising, because a substantial body of evidence implies these processes would be less active in immature brain. The second episode of hypercarbia, from 35 to 65 min postischemia, resulted in a smaller decrease in brain pH compared with the first episode, a result indicating an increase in brain buffering capacity (percentage pH regulation = 79 +/- 29%). This was associated with a parallel decrease in brain lactate content, and therefore acid regulation could be attributed to either continued ion translocation or the consumption of lactate. A mild decrease in brain pH and content of energy metabolites was observed, a finding suggesting that the metabolic consequences of severe postischemic hypercarbia are neither particularly dangerous or beneficial. PMID- 2313287 TI - Two affinity states for [3H]imipramine binding to the human platelet 5 hydroxytryptamine carrier: an explanation for the allosteric interaction between 5-hydroxytryptamine and imipramine. AB - 5-Hydroxytryptamine (5-HT) showed a biphasic effect on the dissociation rate of [3H]imipramine from human platelet membranes: At low concentrations (EC50, approximately 2.5 microM), 5-HT stimulated the rate, as expected for mutually exclusive binding of 5-HT and imipramine; at higher concentrations (EC50, approximately 40 microM), 5-HT reduced this stimulated rate, a result consistent with 5-HT binding at a site that is physically distinct from both the imipramine binding site and the 5-HT transport recognition site of the 5-HT carrier. This modulatory effect could be mimicked by tryptamine, was saturable and independent of Na+ concentration, and could also be demonstrated for detergent-solubilized carriers. Monophasic association kinetics for [3H]imipramine binding were found. Heat stability experiments showed biphasic thermal inactivation curves. These results are consistent with [3H]imipramine binding to two classes of binding sites at the 5-HT carrier on human platelet membranes, with affinities three- to fivefold different. 5-HT can convert the lower-affinity state into the higher affinity state. PMID- 2313288 TI - Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4 phenylpyridinium ion on ATP levels of mouse brain synaptosomes. AB - Mouse brain synaptosomes, essentially devoid of mitochondrial contamination, were used as a model to study the effects of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and its toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) on the levels of ATP of neuronal terminals. Similar to known inhibitors of ATP synthesis, both MPTP and MPP+ caused a dramatic depletion of synaptosomal ATP. This depletion was dose dependent and occurred as a relatively early biochemical event in the absence of any apparent damage to synaptosomal membranes. MPP+ was more effective than its parent compound in decreasing ATP; it induced a significant loss at concentrations (10-100 microM) similar to those it reaches in the brain in vivo. MPTP-induced ATP depletion was completely prevented by the monoamine oxidase B inhibitor deprenyl, which, on the contrary, was ineffective against MPP+. As expected in view of the heterogeneous population of nerve terminals present in our synaptosomal preparations, the catecholamine uptake blocker mazindol did not significantly affect the ATP loss caused by both compounds. Data indicate that (1) administration of MPTP may cause a depletion of ATP within neuronal terminals resulting from the generation of MPP+, and (2) exposure to the levels of MPP+ reached in vivo may cause biochemical changes that are nonselective for dopaminergic terminals. PMID- 2313289 TI - 4-Aminopyridine increases acetylcholine release without diminishing membrane phosphatidylcholine. AB - 4-Aminopyridine (10(-4)-10(-5) M) increased severalfold the release of acetylcholine from rat striatal slices superfused with an eserine-containing, choline-free medium, and caused stoichiometric decreases in the release of choline. It had no effect on tissue acetylcholine and choline levels. Electrical stimulation of the striatal slices increased acetylcholine release without affecting that of choline. Superfusion of the stimulated slices with 4 aminopyridine decreased choline release and increased the ratio of acetylcholine to choline in superfusates. As shown previously, electrical stimulation of the striatal slices decreased their contents of phospholipids, principally phosphatidylcholine; 4-aminopyridine fully protected against these membrane changes. In synaptosomal preparations, 4-aminopyridine was found to enhance the high-affinity uptake of [14C]choline and its conversion to [14C]acetylcholine. This effect on choline uptake may underlie 4-aminopyridine's ability to enhance acetylcholine release in the absence of supplemental choline while suppressing the "autocannibalism" of membrane phospholipids. PMID- 2313290 TI - Neurotensin binding to dopamine. AB - Rotating disk electrode voltammetry at glassy carbon electrodes and ultraviolet/visible spectroscopy were used to demonstrate that dopamine binds to neurotensin with a dissociation constant of 7.5 x 10(-8). By measuring the binding constants of various neurotensin analogs, it was found that the -Arg8 Arg9-portion of the neurotensin sequence is critical for binding dopamine. Neurotensin also formed a complex with 4-ethylcatechol, 4-methylcatechol, 3 methoxytyramine, and norepinephrine. Although changes in the side chain did not alter the binding constant, methoxylation of the catechol moiety significantly increased the dissociation constant. These data along with additional studies of dopamine interactions with arginine derivatives suggest that the guanidino groups of arginine and the catechol hydroxyls of dopamine are responsible for mediating the observed binding. It is hypothesized that the capacity of neurotensin to bind directly to dopamine may be partly responsible for its previously observed antagonism of dopamine-induced locomotor activity. PMID- 2313291 TI - Autoradiographic visualization of A1 adenosine receptors in rat brain with [3H]8 cyclopentyl-1,3-dipropylxanthine. AB - A1 adenosine receptors were labeled in rat brain sections with the antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and visualized at the light microscopic level using autoradiography. The specific binding of [3H]DPCPX to the sections showed the pharmacological characteristics of A1 adenosine receptors and was accompanied by very low levels of nonspecific binding. Whereas GTP had no significant effect on [3H]DPCPX binding to rat brain membranes, the addition of 100 microM GTP increased the apparent affinity of [3H]DPCPX to tissue sections fivefold (from 1.83 to 0.35 nM), enhancing it to the affinity measured in membranes. However, GTP altered neither the binding capacity nor the distribution of binding sites in tissue sections. It is suggested that a competitive antagonism with endogenous adenosine explains the lower affinity of [3H]DPCPX in the absence of GTP. The autoradiographic pattern of [3H]DPCPX binding was characteristic for A1 adenosine receptors. Distinct labeling of the different layers of the cerebellar cortex was shown by photomicrographs generated with the coverslip technique. In addition, several fiber tracts were found to be labeled. The high selectivity for A1 adenosine receptors and low nonspecific binding of [3H]DPCPX, the ability to produce high-resolution autoradiograms, together with the fact that the effects of endogenous adenosine can be eliminated by the addition of GTP make [3H]DPCPX a very useful tool in the autoradiographic study of A1 adenosine receptors. PMID- 2313292 TI - Haloperidol-induced increase in striatal concentration of the tripeptide, Tyr-Gly Gly, provides an index of increased enkephalin release in vivo. AB - A sensitive and specific radioimmunoassay has been developed for the tripeptide, Tyr-Gly-Gly, which has been shown previously to be an extraneuronal metabolite of opioid peptides derived from proenkephalin A. Using this assay, we found a regional variation in Tyr-Gly-Gly immunoreactivity in rat brain, with highest levels in striatum and lowest in cerebral cortex. Intracerebroventricular administration of the aminopeptidase inhibitor, bestatin; produced a threefold increase in Tyr-Gly-Gly immunoreactivity in rat striatum, whereas thiorphan, an enkephalinase inhibitor, produced a 45% reduction in striatal Tyr-Gly-Gly immunoreactivity. These data suggest that the tripeptide, Tyr-Gly-Gly, is in a dynamic state in the brain, and provide further support for the hypothesis that its concentration in specific brain areas may reflect the release of endogenous enkephalins in these brain areas. Further confirmation of the validity of measurements of brain Tyr-Gly-Gly as indices of enkephalin release under conditions of altered neuronal activity was provided by our demonstration that chronic dopamine receptor blockade with haloperidol increased striatal concentrations of both Met-enkephalin and Tyr-Gly-Gly. PMID- 2313294 TI - Effect of peroxide, sodium, and calcium on brain mitochondrial respiration in vitro: potential role in cerebral ischemia and reperfusion. AB - Mitochondrial pyruvate-supported respiration was studied in vitro under conditions known to exist following ischemia, i.e., elevated extramitochondrial Ca2+, Na+, and peroxide. Ca2+ alone (7-10 nmol/mg) decreased state 3 and increased state 4 respiration to 81 and 141% of control values, respectively. Sodium (15 mM) and/or tert-butyl hydroperoxide (tBOOH; up to 2,000 nmol/mg protein) alone had no effect on respiration; however, Na+ or tBOOH in combination with Ca2+ dramatically altered respiration. Respiratory inhibition induced by Ca2+ and tBOOH does not involve pyruvate dehydrogenase (PDH) inhibition since PDH flux increased linearly with tBOOH concentration (R = 0.96). Calcium potentiated tBOOH-induced mitochondrial NAD(P)H oxidation and shifted the redox state of cytochrome b from 67 to 47% reduced. Calcium (5.5 nmol/mg) plus Na+ (15 mM) decreased state 3 and increased state 4 respiratory rates to 55 and 202% of control values, respectively. Sodium- as well as tBOOH-induced state 3 inhibition required mitochondrial Ca2+ uptake because ruthenium red addition before Ca2+ addition negated the effect. The increase in state 4 respiration involved Ca2+ cycling since ruthenium red immediately returned state 4 rates back to control values. The mechanisms for the observed Ca2(+)-, Na(+)-, and tBOOH-induced alterations in pyruvate-supported respiration in vitro are discussed and a multifactorial etiology for mitochondrial respiratory dysfunction following cerebral ischemia in vivo is proposed. PMID- 2313293 TI - Developmental and regional studies of the metabolism of inositol 1,4,5 trisphosphate in rat brain. AB - Coupling of CNS receptors to phosphoinositide turnover has previously been found to vary with both age and brain region. To determine whether the metabolism of the second messenger inositol 1,4,5-trisphosphate also displays such variations, activities of inositol 1,4,5-trisphosphate 5'-phosphatase and 3'-kinase were measured in developing rat cerebral cortex and adult rat brain regions. The 5' phosphatase activity was relatively high at birth (approximately 50% of adult values) and increased to adult levels by 2 weeks postnatal. In contrast, the 3' kinase activity was low at birth and reached approximately 50% of adult levels by 2 weeks postnatal. In the adult rat, activities of the 3'-kinase were comparable in the cerebral cortex, hippocampus, and cerebellum, whereas much lower activities were found in hypothalamus and pons/medulla. The 5'-phosphatase activities were similar in cerebral cortex, hippocampus, hypothalamus, and pons/medulla, whereas 5- to 10-fold higher activity was present in the cerebellum. The cerebellum is estimated to contain 50-60% of the total inositol 1,4,5-trisphosphate 5'-phosphatase activity present in whole adult rat brain. The localization of the enriched 5'-phosphatase activity within the cerebellum was examined. Application of a histochemical lead-trapping technique for phosphatase indicated a concentration of inositol 1,4,5-trisphosphate 5'-phosphatase activity in the cerebellar molecular layer. Further support for this conclusion was obtained from studies of Purkinje cell-deficient mutant mice, in which a marked decrement of cerebellar 5'-phosphatase was observed. These results suggest that the metabolic fate of inositol 1,4,5-trisphosphate depends on both brain region and stage of development. PMID- 2313295 TI - Acetylcholine synthesis and release in the extensor digitorum longus muscle of mature and aged rats. AB - Uptake of labeled choline and its incorporation into acetylcholine (ACh) were assayed at the neuromuscular junction of the extensor digitorum longus (EDL) muscle of rats aged 11 (mature adult) and 27 (aged) months. Under resting conditions, there were no significant differences in muscle ACh or choline levels. Following a 1-h incubation in labeled choline, however, tissue from the younger rats contained significantly greater amounts of labeled choline and labeled ACh; the specific activities of ACh and choline were nearly 10-fold higher in the 11-month-old animals, indicating reduced uptake of labeled choline in the older animals. ACh and choline efflux rates under resting conditions did not change with age, indicating an uncoupling of exogenous choline uptake and ACh efflux in EDL during aging. During nerve stimulation (1 Hz), the amount of labeled choline incorporated into ACh was 150% greater in the aged animals. The specific activity of ACh released during stimulation was correspondingly greater in the 27-month-old animals, although total ACh released did not change appreciably with age. There were no age-related differences in choline acetyltransferase activity. Contrasting results were obtained from diaphragm in previous studies; the linkage between choline uptake and ACh efflux was maintained during rest and stimulation in the diaphragm. Hypothetically, these differences between EDL and diaphragm may be related to their diverse activation patterns: EDL is recruited much less frequently and less regularly than diaphragm, a continually active vital muscle. PMID- 2313296 TI - Syringomyelia and arachnoiditis. AB - Five patients with chronic arachnoiditis and syringomyelia were studied. Three patients had early life meningitis and developed symptoms of syringomyelia eight, 21, and 23 years after the acute infection. One patient had a spinal dural thoracic AVM and developed a thoracic syrinx 11 years after spinal subarachnoid haemorrhage and five years after surgery on the AVM. A fifth patient had tuberculous meningitis with transient spinal cord dysfunction followed by development of a lumbar syrinx seven years later. Arachnoiditis can cause syrinx formation by obliterating the spinal vasculature causing ischaemia. Small cystic regions of myelomalacia coalesce to form cavities. In other patients, central cord ischaemia mimics syringomyelia but no cavitation is present. Scar formation with spinal block leads to altered dynamics of cerebrospinal fluid (CSF) flow and contributes to the formation of spinal cord cystic cavities. PMID- 2313297 TI - Simultaneous VEP and PERG investigations in early Parkinson's disease. AB - To evaluate whether visual evoked potential (VEP) and pattern electroretinogram (PERG) abnormalities may be detectable early in the course of Parkinson's disease (PD) and to assess a possible interdependence between retinal and cortical potentials, simultaneous VEP and PERG were carried out in nine patients with early PD. The mean (SD) duration of the disease was 10 (6) months. None of the patients had been previously treated with levodopa or other anti-parkinsonian drugs. The results show VEP and PERG abnormalities that are spatial stimulus dependent, with higher frequencies being more involved and also indicate that VEP changes are not entirely dependent on alterations at the retinal level. PMID- 2313298 TI - Disturbances in ocular sympathetic function and facial blood flow in unilateral migraine headache. AB - The relationship between thermographic asymmetry in various parts of the face and indices of ocular sympathetic outflow was examined in 80 patients with unilateral migrainous headache. Both during and between episodes of headache, the pupil on the symptomatic side dilated more slowly and less extensively in darkness than the opposite pupil, indicating that ocular sympathetic outflow was compromised in some patients. In such cases the upper forehead and orbital region were warmer on the symptomatic side during migraine. In contrast to these signs of a reduction in cervical sympathetic outflow, eyelid separation was greater on the symptomatic side in patients with headache on the side that was usually affected. During the headache-free interval no consistent thermographic asymmetry was detected and eyelid separation was similar on both sides. These findings suggest that extracranial vascular changes and ocular sympathetic dysfunction during migraine are secondary to activation of trigeminal-vascular reflexes or to antidromic release of vasoactive substances from trigeminal nerve terminals. A secondary deficit in the sympathetic pathway to the symptomatic pupil could also prevent the expression of an increase in sympathetic outflow during headache. PMID- 2313299 TI - Recovery of elbow function in voluntary positioning of the hand following hemiplegia due to stroke. AB - Elbow movement during voluntary positioning of the hand (with the arm supported against gravity) is described in a longitudinal study of five patients recovering from hemiplegia due to stroke. Over a twelve month period, four of the patients improved their speed of movement, three exhibiting slightly better recovery of elbow extension, one of flexion. In some instances co-contraction of the elbow agonist and antagonist (measured just before the onset of movement) decreased with time after stroke. The effects of contrasting movements at the shoulder on elbow movement were also studied. Estimates of recovery were generally similar whether patients kept the shoulder still or made movements that were synergic or counter-synergic to those of the elbow. PMID- 2313300 TI - Somatosensory findings in postherpetic neuralgia. AB - Somatic sensory perception thresholds (warm, cold, hot pain, touch, pinprick, vibration, two-point discrimination), allodynia and skin temperature were assessed in the affected area of 42 patients with unilateral postherpetic neuralgia (PHN) and 20 patients who had had unilateral shingles not followed by PHN (NoPHN), and in the mirror-image area on the other side. There was no difference between the two groups for age or length of time after the acute herpes zoster infection. The PHN group showed significant changes in all sensory threshold measurements when the affected area was compared with the mirror-image area on the unaffected side, while the NoPHN group exhibited no threshold changes. Mechanical allodynia was present in 87% of the PHN group; half of the 12 patients with ophthalmic PHN showed extension of allodynia to the maxillary distribution. No differences in skin temperature were recorded between affected and unaffected regions in either group. Our findings show a deficit of sensory functions mediated by both large and small primary afferent fibres and also suggest major central involvement in the pathophysiology of the condition. If PHN does not occur following acute herpes zoster, recovery of neural functions appears to be good. PMID- 2313301 TI - Neuropsychological assessment in patients with relapsing-remitting multiple sclerosis and mild functional impairment: correlation with magnetic resonance imaging. AB - Forty one moderately impaired patients with clinically confirmed multiple sclerosis (MS) and a relapsing-remitting course were submitted to a neuropsychological battery and magnetic resonance imaging (MRI) to correlate the neuropsychological performances with the degree of cerebral demyelination. The neuropsychological results were indicative of a very mild overall impairment. The patients were subdivided into two groups (extensive periventricular demyelination or discrete lesions on MRI) and the results of neuropsychological tests compared. Patients with extensive periventricular demyelination had an inferior performance on concept formation, non-verbal reasoning and verbal memory tests. PMID- 2313302 TI - Some clinical and pathologic observations on chronic myelopathy: a variant of multiple sclerosis. AB - Four patients with progressive demyelinating myelopathy with symptoms spanning six to 25 years are described. There was no clinical evidence of dissemination of lesions in the central nervous system. Radiological evidence of dissemination was present in two cases; in one this was absent at the time of presentation and was only demonstrated after six years of progressive unifocal disease. In one case, pathological examination revealed a solitary area of chronic demyelination. In all cases but one, oligoclonal bands were detected on cerebrospinal fluid (CSF) electrophoresis. Some cases of chronically progressive myelopathy result from focal demyelination in the absence of a second lesion demonstrable by clinical, radiographic or necropsy examination. PMID- 2313303 TI - Lateralisation of cortical function during cognitive tasks: regional cerebral blood flow studies of normal individuals and patients with schizophrenia. AB - To assess cognitively-related regional asymmetries of brain function, regional cerebral blood flow (rCBF) was determined by the xenon inhalation method while normal subjects performed 10 different tasks and also while they were at rest. In addition to healthy subjects, patients with schizophrenia were also studied. A total of 447 rCBF studies were carried out during the following conditions: the Wisconsin Card Sort Test, a numbers matching test, a symbols matching test, Raven's Progressive Matrices, an auditory discrimination test, an auditory control task, two versions of a visual continuous performance task, line orientation, semantic classification, and resting. On the whole, those tasks that seem to require or allow for internal verbalisation resulted in the greatest activation of the left hemisphere compared with the right; right hemisphere activation predominated only in the two tasks primarily involving attention and vigilance. Furthermore, a consistent regional topography of normal cerebral functional laterality was seen: under most conditions left prefrontal cortical activity exceeded that of right prefrontal cortex; during all non-auditory tasks, parieto-occipital cortical activity had an opposite pattern-greater right than left. During most conditions the schizophrenic patients displayed the same pattern. While several cognitively specific between-group differences were found, no single cortical region was consistently implicated and no specific direction of abnormal asymmetry predominated. These data suggest that there is a predominant task-independent functional pattern of cortical activity emphasising relatively greater left anterior and right posterior activation. This pattern may reflect the verbal and attentional primacy of these areas, respectively. PMID- 2313305 TI - Oral dyskinesias associated with bilateral thalamo-capsular infarction. AB - Involuntary mouthing movements indistinguishable from neuroleptic-induced tardive dyskinesia followed stroke in a woman whose computed tomographic (CT) scan showed bilateral thalamo-capsular infarction. PMID- 2313307 TI - Numb chin syndrome in the elderly. PMID- 2313306 TI - HLA antigens in chronic inflammatory demyelinating polyneuropathy. AB - HLA typing of 71 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) showed an overall increase in frequencies of HLA-A3, -B7, -DR2 as well as concomitantly decreased frequencies of HLA-44 and DR7. The strongest associations were seen with HLA-DR2, -DR7 and -B44 in CIDP overall, although they did not reach statistical significance. PMID- 2313304 TI - A quantitative study of the neurofibrillary tangles and the choline acetyltransferase activity in the cerebral cortex and the amygdala in Alzheimer's disease. AB - A quantitative study has been made of the number of neurofibrillary tangles and of the choline acetyltransferase activity in several sites in the cerebral hemispheres of eight patients who had had Alzheimer's disease. The neurofibrillary tangles were maximal in structures in the medial temporal lobe (uncus, amygdala, hippocampus and parahippocampal gyrus), severe in the neocortex on the lateral surface of the temporal lobe, moderate in the "association cortex" of the parietal and frontal lobes and minimal in primary somatic and visual sensory areas. There was a significant decrease in choline acetyltransferase activity in almost all areas, and the means of the percentage decreases for the different groups of areas correlate well with the counts of the neurofibrillary tangles. These results support the hypothesis that the pathological process in Alzheimer's disease may spread along a sequence of corticocortical connections between the main sensory areas and the hippocampal formation. The disease process may also spread along the reciprocal connections between the amygdala and the neocortex because the numbers of tangles in different areas of the neocortex closely parallel the density of their connections and the amygdala. PMID- 2313308 TI - Methylprednisolone therapy in tropical spastic paraparesis. PMID- 2313309 TI - Increased amplitude of F-response in Lambert-Eaton myasthenic syndrome. PMID- 2313310 TI - Trunkal myoclonus with spontaneous priapism and seminal ejaculation in Wilson's disease. PMID- 2313311 TI - Subarachnoid haemorrhage related to a lumbosacral fusion: a case report. PMID- 2313312 TI - Spinal arteriovenous malformation unmasked during intravenous urography. PMID- 2313314 TI - Precision and insight. PMID- 2313313 TI - Subcutaneous apomorphine in the treatment of Parkinson's disease. AB - Apomorphine a dopamine receptor agonist was given subcutaneously to 57 levodopa treated parkinsonian patients with refractory off-period disabilities for a median period of 16 months. In 30 given intermittent suprathreshold injections the mean number of hours spent in a disabling off state fell from 6.9 to 2.9. Similar benefit was observed in 21 patients receiving continuous infusions with additional boluses on demand by mini-pump (mean reduction of hours off from 9.9 to 4.5). Twelve patients have been treated for over two years without tachyphylaxis or loss of response. The incidence of neuropsychiatric side-effects has been low (7%). Six patients failed to show a sustained worthwhile response; severe disabilities during "on" periods being the major problem. Subcutaneous apomorphine is proposed as an effective treatment for patients with incapacitating "off" period disabilities refractory to oral medication and should be considered before experimental implantation procedures. PMID- 2313315 TI - The individual over time: time series applications in health care research. AB - This paper presents a summary and a brief theoretical introduction to time series ARIMA modeling of single subject data. Time series, a statistical technique that may be appropriate when data are measured repeatedly and at nearly equal intervals of time, has potential research applications in the study of chronic diseases such as diabetes, hypertension, and herpes simplex. Both intervention models and multivariate models are covered, with examples illustrating the utility of time series techniques in chronic disease research. Time series modeling of a subject with diabetes before and after being placed on a regimen of chlorpropamide is used to demonstrate the potential of intervention analysis. Multivariate time series techniques are illustrated by modeling the relationship between exercise and blood glucose, and by modelling the relationship between psychosocial distress and lymphocyte subsets of the cellular immune system. PMID- 2313316 TI - "Rainbow reviews." IV: Recent publications of the National Center for Health Statistics. AB - I am always impressed at the wealth of interesting and useful information available from the NCHS, if one knows where to look. The Center tries to adapt to the changing needs of the potential users of their data, including health planners and policy analysts, and academicians. This is illustrated by the increasing emphasis on medical care utilization, especially in long term care, on disease prevention and health promotion issues and on international comparisons. Clinical investigators should be familiar with the NCHS reports, if only to avoid duplication of effort. But beyond that, the information they present can be used to develop hypotheses, estimate variances for sample size determinations, and provide useful model instruments and methods. Beyond that, the NCHS does not analyze and report exhaustively on these data, if only because of lack of resources, so that it makes most of these data available for further research at a nominal charge. Many doctoral dissertations have been based on these tapes as the primary data source for detailed content analysis and/or for methodologic innovation. PMID- 2313317 TI - Risk factors for breast cancer according to age at diagnosis in a French case control study. AB - In a French case-control study of 1010 women with breast cancer and 1950 controls with nonmalignant disease, the variations of the effects of 8 risk factors for breast cancer as a function of age at diagnosis, were analysed by tests of homogeneity and trend. The risks associated with a late age at first full-term pregnancy and with nulliparity were different between age-groups (test of homogeneity: p = 0.03), and the highest risks for these two factors were observed in women 45-54 years old. The risks associated with Quetelet index were also found to vary with age at diagnosis (test for trend: p = 0.008). A high Quetelet index decreased the risk of breast cancer in the younger age-groups; this decrease of risk became progressively less important with advancing age, and no such effect was found in the oldest age-group. Inverse results were observed for a tall stature (test for trend: p = 0.04): a tall stature increased the risk of breast cancer in the younger age-groups, and the figures suggested a reverse effect in the oldest group. No large variation with age was found for the effects of age at menarche, history of breast cancer death in mother or sisters, prior biopsy for benign breast disease, and weight. In conclusion, the relative importance of certain risk factors for breast cancer is closely related to age at diagnosis. Nulliparity and a late age at first birth appear to be major risk factors only for middle-aged women, whereas a low Quetelet index and a tall stature appear to increase the risk of breast cancer only for younger women. PMID- 2313318 TI - A large-scale prospective cohort study on diet and cancer in The Netherlands. AB - In 1986, a prospective cohort study on diet and cancer was started in The Netherlands. The cohort (n = 120, 852) of 55-69 year old men (48.2%) and women (51.8%) originates from 204 computerized municipal population registries. At baseline, participants completed a self-administered questionnaire on diet and potential confounding variables. In addition, about 67% of the participants provided toenail clippings. Cancer follow-up consists of record linkage to a pathology registry and to cancer registries. The initial interest is in stomach, colorectal, breast and lung tumors. A case-cohort approach is applied, in which detailed follow-up information of a random subcohort (n = 5000) provides an estimate of the person-time experience of the cohort. Exposure data of the subcohort will be combined with those of incident cases, yielding exposure specific incidence rate ratios. The intraindividual variation in determinants is estimated by annually repeated measurements (n = 250) within the subcohort. The rationale, efficiency aspects and study characteristics are discussed. PMID- 2313319 TI - The Kidney Disease Questionnaire: a test for measuring patient knowledge about end-stage renal disease. AB - Two studies report on the development of the Kidney Disease Questionnaire (KDQ) as a test for measuring patient knowledge about end-stage renal disease and its treatment. The KDQ is available in a 26-item version or as two parallel 13-item tests. Psychometric evaluations indicate that all versions show high levels of reliability. Initial validity tests are also promising. The KDQ is able to discriminate individuals well informed about kidney disease and its treatment from those who are not so well informed. It is also sensitive to the effects of an experimental education program and to ESRD-related knowledge that is acquired as a result of starting dialysis. Data and issues related to the administration, readability, demographic correlates, and a French translation of the KDQ are also presented and discussed. PMID- 2313320 TI - Biological markers: broadening or narrowing the scope of epidemiology. PMID- 2313321 TI - Cruel cacophony, boisterous beeper. PMID- 2313322 TI - Falling between the cracks: a student experience in providing home care for underserved community residing elders. PMID- 2313323 TI - The homeless: social isolates. AB - Within the last 10 years, homelessness has emerged as one of the leading social problems in the United States. This article contains the findings of a descriptive study of the characteristics and health status of a homeless population in a southeastern city. The homeless population is of interest to nurses because it is representative of a specific disadvantaged group, seriously at risk for a myriad of physical and mental problems. The theoretical model, Social Disaffiliation, can serve as a basis for intervention with a variety of underserved or unserved population groups and the data presented provide opportunities for designing nursing intervention strategies. The study was conceived as a way to gather empirical evidence about the specific health-care needs of the community's homeless, to generate a data base on which to estimate that need, and to use the findings to support the establishment of an innovative practice model, a nurse-managed clinic. The literature suggests that on-site clinics, located in emergency shelters, are effective approaches to providing acceptable and accessible health care to the homeless. Nurses are well prepared to be a key part of the solution to one of the most serious problems facing health care in the U.S. today. PMID- 2313324 TI - Expanding community health nursing roles to meet health-care needs of frail elderly. An adult learning model. AB - The increased training needs for community health nurses (CHNs) working with frail elderly offer a variety of challenges in staff development. Santa Clara County addressed these challenges with an innovative model, and geriatric assessment skills building program presented to 40 CHNs. The model uses a team teaching approach, a preceptorship and adult learning theory, making it readily adaptable to a variety of community health settings. PMID- 2313325 TI - Incompetency laws in need of review. PMID- 2313326 TI - Sensory impairment: factor x in providing nursing care to the older adult. PMID- 2313327 TI - The value of studying cancer families. PMID- 2313328 TI - Identification of factors associated with high breast cancer risk in the mothers of children with soft tissue sarcoma. AB - Information on the past medical history of the mothers of a population-based series of 177 children with soft tissue sarcoma was obtained by interview and from medical records. Eight mothers developed breast cancer, six premenopausally, compared with 3.26 expected (P = .04), but no excess of other types of cancers was detected. High breast cancer risk was associated with the following factors in the index child: age at diagnosis less than 24 months (relative risk [RR], 7.84), embryonal rhabdomyosarcoma (RR, 3.74), and male sex (RR, 3.02). Characteristics in the mother associated with high breast cancer risk were the following: late age at first birth (RR, 5.13), late age at birth of index child (RR, 5.69), and high birth-rank order of index child (RR, 4.08). The results suggest there may be a subset of childhood soft tissue sarcoma with a predominantly genetic etiology. The association between premenopausal breast cancer in the mother, late age at birth of index child, and early onset of soft tissue sarcoma in the index child suggests that these three events are not independent and that interactions between genetic and other factors may be important. The identification of a group of women at high risk for breast cancer affords an opportunity for screening and early detection. The study of cancer family syndromes may provide insights into underlying mechanisms in cancer genetics. PMID- 2313329 TI - Why are local recurrences after breast-conserving therapy more frequent in younger patients? AB - The influence of patient age on risk of recurrence in the breast was retrospectively studied in 496 stage I-II invasive ductal carcinomas treated by macroscopically complete primary tumor excision followed by radiotherapy. With a median follow-up of 71 months, local recurrence occurred in 13 of 62 (21%) patients younger than 40 years, compared with 48 of 434 (11%) older patients (P less than .025). Cox multivariate analysis of 18 parameters identified four that significantly determined risk: major lymphocytic stromal reaction (MCR), unsatisfactory resection margins, increasing histologic grade, and extensive intraductal cancer (DCIS) within the primary tumor. Compared with older patients, those younger than 40 years had tumors that more often exhibited MCR (36% v 20%, P less than .01), histologic grade 3 (42% v 28%, P less than .025), and very extensive DCIS (21% v 6%, P less than .001). The status of resection margins did not differ significantly between younger and older patients. Restriction of Cox analysis to patients younger than 40 indicated that risk was adequately described by MCR and percentage of DCIS, without consideration of grade or margins. For patients younger than 40, local failure occurred in four of five (80%) tumors with both MCR and more than 50% DCIS, in eight of 25 (32%) with either, and one of 32 (3.1%) with neither of these morphologic features. This study suggests that the higher local failure risk observed in patients younger than 40 years reflects the greater prevalence of certain morphologic characteristics in breast cancers in younger patients. Age itself does not appear to be an independent determinate of risk. PMID- 2313330 TI - Small noncleaved cell lymphoma in adults: superior results for stages I-III disease. AB - Small noncleaved cell lymphoma (SNCCL), a rare lymphoma in adults, is associated with not only a rapid complete response (CR) to chemotherapy but also with the potential to rapidly relapse both systemically and in the CNS. We treated 44 assessable adults with two similar protocols, consisting of three sequential chemotherapy combinations and intrathecal prophylaxis with methotrexate and cytarabine. The overall CR rate was 80%; it was 100% in patients with Ann Arbor (AA) stages I-III disease and 57% in those with stage IV disease. The overall survival (OS) rate at 5 years was 52%. The overall 5-year freedom from tumor mortality (FTM) rate was 63%; it was 95% for patients with AA stages I-III disease, and 29% for those with stage IV disease. Stepwise multivariate analysis of factors associated with remission duration and survival indicated that advanced-disease stage and age of 40 years or over were predictors of poor prognosis. Twelve patients with positive human immunodeficiency virus (HIV) serology were also included in this series. They had an 83% CR rate and an 83% 5 year FTM, but only a 36% 5-year OS; most deaths were secondary to opportunistic infection. Histologic subtype (Burkitt's lymphoma [BL] or non-Burkitt's lymphoma [NBL]) did not correlate with patient age, site of tumor presentation, response to therapy, or survival. Both protocols achieved comparable results. The approach used in these protocols is highly effective for patients with early staged disease, regardless of their HIV status; however, better therapy is necessary for those with SNCCL presenting in an advanced stage. PMID- 2313331 TI - Prognostic factors for patients relapsing after radiotherapy for early-stage Hodgkin's disease. AB - Prognostic factors were analyzed retrospectively in 109 patients who relapsed after treatment with radiation only for Hodgkin's disease. Factors analyzed included initial stage, age, time to first relapse, histology, sex, extent of initial irradiation, sites of relapse, relapse stage (RS), average relative dose intensity (ARDI) of chemotherapy, and type of salvage therapy. Ninety-three percent of the patients received either standard or modified mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). With a median follow-up of 8.3 years, the actuarial survival and freedom from second relapse (FF2ndR) was 57% at 10 years. The extent of disease at the time of relapse, or so-called RS was found to be the single most important prognostic factor. Nearly 90% of patients with RS IA or IEA (favorable group) were disease free, and nearly 60% of patients with RS IIA, IIEA, or IIIA (intermediate group) were disease free compared with only 34% of patients with B symptoms or stage IV disease (unfavorable group). In a subset analysis, the use of combined modality therapy (CMT) was associated with an improved FF2ndR and survival in patients from the intermediate and unfavorable relapse groups. Age greater than 50 years was associated with an increased risk of second relapse and a lower survival. The other factors analyzed appeared to be of no independent prognostic value. PMID- 2313332 TI - The role of autologous bone marrow transplantation in 46 adult patients with non Hodgkin's lymphomas. AB - Forty-six patients with non-Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation (ABMT) in two different institutions. All patients were pretreated with conventional chemotherapy. Three different conditioning regimens were used, and 20 patients underwent bone marrow purging. Twelve patients were treated in first complete remission (CR); eight are in unmaintained CR 8 to 104 months after ABMT. Five patients were grafted in first partial remission (PR) after conventional therapy; all achieved CR, and all remain in prolonged CR (first CR for four patients, second CR for one patient). Of 21 patients with chemosensitive relapses, 13 patients are in prolonged unmaintained CR 8 to 94 months after ABMT. Eight patients with resistant disease remained uncured by ABMT; all eight died, six from progressive illness and two from toxicity. The current 3-year disease-free probability is 60% for all patients, 0% for refractory disease; 82% for first PR or CR, and 60% for sensitive relapses (SRs). These results confirm the efficacy of ABMT in the treatment of chemosensitive NHL with bad prognosis. PMID- 2313333 TI - Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle. AB - Between October 1979 and January 1988, 101 patients with malignant lymphoma who failed initial induction treatment or relapsed received high-dose combination chemotherapy or chemoradiotherapy followed by infusion of autologous bone marrow. Twenty-eight of the 101 patients survive, 18 of whom are disease-free for a median of 26 (range, 12 to 66) months. The 5-year actuarial probabilities of survival, event-free survival (EFS), and relapse from transplantation were 20%, 11%, and 84%, respectively. Multivariate analysis showed that the likelihood of EFS was decreased among patients transplanted with a Karnofsky score of less than 80%. Recurrent lymphoma after transplant was the most important cause of treatment failure with 36 of 62 relapses occurring within 100 days from marrow infusion. Early, but not late relapse, was more frequent in patients transplanted for advanced lymphoma, and both early and late relapses were increased among patients with impaired pretransplant clinical performance or high-grade histology of lymphoma. Ten patients who relapsed post-transplant are alive, seven in remission. Further improvement of these results will require earlier transplantation, improved preparative regimens, or early posttransplant therapy. PMID- 2313334 TI - Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study. AB - Cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) is a widely used conditioning regimen in autologous bone marrow transplantation (ABMT) of patients with refractory and relapsed lymphoma. However, the maximum-tolerated dose (MTD) of these agents when used in combination has not been systematically explored. We treated 58 patients (28 with non-Hodgkin's lymphoma [NHL], 30 with Hodgkin's disease [HD]) at seven dose levels of CBV. Doses were cyclophosphamide 4,500 to 7,200 mg/m2, BCNU 450 to 600 g/m2, and VP-16 1,200 to 2,000 mg/m2. The MTD was cyclophosphamide 7,200 mg/m2, BCNU 450 mg/m2, and VP-16 2,000 mg/m2. Six hundred milligrams per square meter of BCNU was associated with five of 18 cases of interstitial pneumonitis versus two of 40 at 450 mg/m2 (P = .02). Treatment related mortality was 5% at dose levels less than or equal to the MTD and 22% at the highest dose. In this heavily pretreated patient population, most of whom had high volume residual disease, complete responses (CRs) to CBV and ABMT occurred in 25% of assessable patients with NHL and 43% of patients with HD. Thirteen of 28 patients with NHL and 14 of 30 with HD remain free from disease progression with median follow-up of 212 and 215 days, respectively. CBV can be administered with acceptable toxicity over a wide range of doses to patients with refractory and relapsed lymphoma. PMID- 2313335 TI - Phase II study of cytarabine and etoposide in children with refractory or relapsed non-Hodgkin's lymphoma: a study of the French Society of Pediatric Oncology. AB - Twenty-five children or adolescents with relapsed or refractory non-Hodgkin's lymphoma (NHL) were included in this phase II study of the combination of cytarabine (ARA-C) 50 mg/m2/d by 12 hours continuous infusion day 1 to day 5, ARA C 3 g/m2/d in 3 hours day 1 to day 4, and etoposide (VP 16) 200 mg/m2 daily from day 1 to day 4. Twelve patients had B-cell, 12 T-cell, and one non-T, non-B-cell lymphoma; according to Murphy's staging system, 15 had stage III and nine stage IV disease with bone marrow involvement at diagnosis. All had previously received ARA-C by push or continuous infusion. Two patients had received epipodophyllotoxins. At the time of the study, three children had initial refractory disease, 18 were in first relapse (14 on therapy), two in first refractory relapse, and two in second relapse (on therapy). The overall response rate (RR) was 60%: eight complete responses (CRs), seven partial responses (PRs) (two became CRs after a second course). The RR was 66% (four CRs plus four PRs) in B-cell and 54% (four CRs, three PRs) in non-B-cell NHL. It was 20% (one PR per five patients) in initial or relapsed refractory disease. In four patients with measurable CNS disease, there were three CRs. Duration of response was nonassessable since all the responding patients received high-dose polychemotherapy followed by autologous bone marrow transplantation (ABMT) (five are alive with long follow-up [FU]). Toxicity was marked mostly by pancytopenia for 2 weeks, and half the patients encountered a grade-3 infection. One severe diarrhea was observed. In conclusion, high-dose ARA-C (HD-ARA-C) and VP 16 are an effective regimen in relapsed NHL, especially with CNS disease, and its toxicity is acceptable with regards to the prognosis of the disease. PMID- 2313336 TI - A comparison of four staging systems for localized and regional neuroblastoma: a report from the Childrens Cancer Study Group. AB - Four major staging systems have been used to estimate the prognosis for children with local and regional neuroblastoma (NBL). Data obtained at diagnosis for 251 neuroblastoma patients from two Childrens Cancer Study Group (CCSG) studies were analyzed according to staging systems of the CCSG, St Jude Children's Research Hospital, the Pediatric Oncology Group (POG), and the Union Internationale Contre le Cancer (UICC) tumor-nodes-metastasis (TNM) system. The most significant variables were found to be age, tumor stage, extent of tumor removal, transgression of the midline by tumor infiltration, and site of primary tumor. Involvement of lymph nodes per se was not a bad prognostic sign unless associated with extension beyond the midline, the latter being the single most important prognostic variable. All four staging systems had value for prognostication and all identified with accuracy the low stage patient (stage I, stage A) who fares well (greater than or equal to 87% survival). The CCSG definition of stages II and III disease discriminated prognostic groups best among the remaining patients, and was able to identify the child with local-regional NBL with poor survival. The estimated 5-year survival rates for children with regional tumor (stage III, IIIA[N]), according to the four systems were 44%, 74%, 74%, and 74% for the CCSG, St Jude, POG, and UICC methods, respectively. We conclude that all four staging systems effectively define good-prognosis patients with localized disease but that the CCSG staging system most accurately identifies patients with regional tumor who have a poor outcome. PMID- 2313337 TI - Treatment of hairy cell leukemia with alternating cycles of pentostatin and recombinant leukocyte A interferon: results of a phase II study. AB - Fifteen patients with hairy cell leukemia (HCL) were treated with deoxycoformycin (pentostatin; dCF) (4 mg/m2 intravenous [IV] every week x 3) and recombinant interferon-alpha 2a (rIFN-alpha 2a) (3 x 10(6) units subcutaneously [SC] daily x 4 weeks) in alternating months for a total of 14 months. Eleven patients had undergone splenectomy; four had received prior systemic therapy with chlorambucil and/or steroids. All 15 are evaluable for toxicity and peripheral blood response, while 14 are assessable for bone marrow response. Toxicity was tolerable with grade 3 or 4 nausea and vomiting in three patients, neutropenic fevers in five, transient but significant depression in eight, and localized cutaneous herpes zoster in four. Circulating hairy cells were undetectable by the end of the first month in 10 of 13 patients, and by the end of the second month in the other three. Fourteen patients had bilateral bone marrow biopsies performed at baseline after 6 months of treatment, at the end of treatment (14 months), and at 6-month intervals during follow-up. Before treatment, all patients had hypercellular marrows with hairy cels replacing normal marrow elements; all showed at least a 95% clearing of their hairy cell infiltrate by 6 months of therapy. However, small collections of residual hairy cells could be detected intermittently on at least one side of bilateral samples in all patients. All patients have completed treatment with a median duration of follow-up off therapy of 27 months (range, 15 to 31 months). To date, all peripheral counts and serum soluble interleukin-2 receptor (sIL2R) levels remain stable, and no patient has had progression of the hairy cell infiltrate in the bone marrow. Although no patient achieved a pathologic complete response, alternating monthly cycles of dCF and rIFN-alpha 2a produced durable partial remissions (PRs) in all patients. Continued follow-up is required to determine the length of such remissions. PMID- 2313338 TI - Bone marrow stem cell disorders and mitolactol. PMID- 2313339 TI - Cervix cancer: too many patients. PMID- 2313340 TI - A science for shrinking seminoma? PMID- 2313341 TI - MOPP dose intensity and survival: flawed analysis. PMID- 2313342 TI - Role of Na-K pump potassium regulation and IPSPs in seizures and spreading depression in immature rabbit hippocampal slices. AB - 1. Using the immature (8-12 days postnatal) rabbit hippocampal slice preparation, we investigated regional extracellular potassium concentration [( K+]o) changes that occur during spontaneous and evoked spreading depression (SD) episodes. We report here a difference between the CA1 and CA3 cell populations in the immature hippocampus with regard to 1) resting [K+]o, 2) magnitude of the [K+]o change during seizurelike events and SDs, and 3) susceptibility to SD episodes. Experiments were also performed to elucidate the roles that the Na-K pump and synaptic inhibition play in controlling SD onset, duration, and recovery. We demonstrated a major role for potassium regulation by the Na-K pump and a lesser modulatory role for inhibitory postsynaptic potentials (IPSPs) in preventing SD in the CA3 region. 2. Simultaneous intra- and extracellular recordings were made in the CA1 and CA3 regions of the immature rabbit hippocampus during spontaneous or evoked SD, while potassium ion-sensitive microelectrodes (K-ISMs) monitored changes in [K+]o. The CA1 region had 1) a higher frequency of spontaneous SD episodes than CA3, 2) a lower threshold to potassium-triggered SD, 3) a longer duration SD episode, and 4) smaller post-SD membrane potential and [K+]o undershoots (below the original resting membrane potential and resting [K+]o). 3. During the onset of a SD episode in the CA1 region, the local [K+]o rose either before or at the same time as the membrane potential depolarization. 4. In the CA3 region, spontaneous ictallike events consisting of tonic cell depolarization with repetitive activity followed by clonic afterdischarges were more likely to occur than SD episodes. During these ictallike episodes, [K+]o rose above the 10- to 12-mM ceiling level reported for adult CNS tissue during seizures. Increases in [K+]o evoked by repetitive stimulation were regulated at a lower level in CA3 (average [K+]o rise to 11.4 mM) than in CA1 (average [K+]o rise to 18.3 mM). 5. In CA3, bath application of 10 microM bicuculline or 3.4 mM penicillin did not change the frequency of spontaneously occurring SDs or the SD response threshold to local pressure ejection of 2 M KCl. However, blockade of IPSPs did lead to lower thresholds for SD or seizurelike episodes elicited by stimulation of the mossy fibers. 6. A single application of ouabain (10 microM) to CA3 by local pressure ejection caused a slow rise in local [K+]o measured with K-ISMs. The ouabain treatment also increased the frequency of spontaneous postsynaptic potential activity and decreased the amplitude and duration of CA3 pyramidal cell afterhyperpolarizations (AHPs).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313343 TI - Effects of midbrain and medullary stimulation on spinomesencephalic tract cells in the cat. AB - 1. The effects of electrical stimulation at different rostrocaudal levels of the midbrain, and at sites in the rostral medulla ipsilateral and contralateral to spinal recording sites, were evaluated against the responses of 46 cells belonging to the cat spinomesencephalic tract (SMT). 2. Inhibitory and/or excitatory effects of brain stem stimulation were observed on SMT cells that responded best (26 cells) or exclusively (12 cells) to noxious mechanical or thermal stimuli, as well as on 7 cells responding only to tap and/or stimulation of deep tissues. Recording sites for 32 cells were located in laminae V-VIII (27 cells) and laminae I-III (5 cells). 3. Midbrain stimulation sites were located in the superior colliculus, central gray (CG), red nucleus, and the midbrain reticular formation. Both inhibitory-only and excitatory-only effects were observed, although the most common effect of midbrain stimulation was excitation followed by inhibition (mixed effects). The effects of stimulation at different midbrain levels were determined for each cell. Stimulation in the caudal, middle, or rostral midbrain was often found to exert different effects on the same SMT cell. 4. Stimulation in the rostral medulla at sites located in nucleus raphe magnus (NRM), nucleus reticularis gigantocellularis, and nucleus reticularis magnocellularis produced the same complement of effects observed with midbrain stimulation. Excitation followed by inhibition was the most common effect observed. 5. Stimulus intensities required to produce excitatory or inhibitory effects from midbrain were 114 +/- 85 (SD) microA and 210 +/- 91 microA, respectively. Stimulus currents required to produce excitatory or inhibitory effects from medullary stimulation sites were 124 +/- 56 microA and 70 +/- 60 microA, respectively. The mean currents required to produce mixed effects were 221 +/- 120 microA (midbrain) and 127 +/- 71 microA (medulla). Increasing the stimulus intensity used to evaluate brain stem effects increased the magnitude and duration of effects for 33 cells. Mixed effects were observed on 11 cells at stimulus intensities greater than those required to produce inhibitory-only effects. 6. Significant differences were found between the latencies of excitation and inhibition produced from different brain stem levels. These differences suggest that midbrain and medullary stimulation activate descending pathways with a wide range of conduction velocities and/or supraspinal and spinal connectivities. 7. The spinal trajectory of pathways contributing to the varied effects of brain stem stimulation as well as the complex receptive fields (RFs) of SMT cells were evaluated by the placement of lesions in the cervical spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313344 TI - Functional properties of afferent fibers supplying reproductive and other pelvic organs in pelvic nerve of female rat. AB - 1. Electrophysiological techniques were used to characterize responses of afferent fibers in pelvic nerve of adult, virgin female rats to mechanical or chemical stimulation of internal reproductive organs and to mechanical stimulation of other pelvic organs. 2. In an in vivo barbiturate-anesthetized preparation, pelvic nerve afferent fibers responded to a wide variety of mechanical stimulation applied to restricted regions of the vaginal canal, caudal uterus (body and cervix), bladder, ureter, colon, or anus. 3. Single-fiber mechanoreceptive fields were invariably confined to a single organ. Notably, responses could be evoked not only by gentle stimulation of the unit's receptive field directly on the organ itself, but also by stimulating the field indirectly with intense stimulation through the appropriate part of a contiguous organ. This innervation feature is consistent with the separability of pelvic organ functions under innocuous conditions but their confusion under noxious ones. 4. Receptive fields on the reproductive organs extended from the caudal edge of the vagina to the uterine body (including the cervix) but were most often located in the fornix (vaginocervical junction). Most units had no or low levels of spontaneous activity. Their responses to mechanical stimuli were usually slowly or moderately adapting and time-locked to the stimulus. 5. Fibers with vaginal receptive fields (including the fornix) responded best either to vaginal distension with a balloon or, more often, to a probe moving along the internal vaginal surface in a direction toward the cervix. They were observed most frequently during the proestrus stage of the rat's estrous cycle. These fibers, therefore, seem particularly suited for relaying information about stimuli that occur during mating. 6. Fibers with receptive fields on the uterine cervix and body responded best to static pressure and were observed less frequently than those with vaginal fields, regardless of estrous stage. They were, however, sensitized by hypoxia. In addition, irritation of the uterus increased the probability of observing them. These fibers, therefore, may exert their primary function during reproductive conditions different from those of virgin rats, such as parturition. 7. Response activity of most of the mechanoreceptive afferent fibers supplying reproductive organs increased as the stimulus intensity increased into the noxious range; i.e., into a range in which the stimulus momentarily produced ischemia at the stimulus site. In addition, in an in vitro preparation, pelvic nerve fibers responded in a dose-dependent manner to injections through the uterine artery of bradykinin (BRAD) as well as to other algesic chemicals, 5 hydroxytryptamine (5-HT) and KCl.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313345 TI - Location and morphology of dorsal spinocerebellar tract neurons that receive monosynaptic afferent input from ankle extensor muscles in cat hindlimb. AB - 1. The present experiments were carried out to investigate the morphology and somatotopic location of dorsal spinocerebellar tract (DSCT) neurons that receive monosynaptic group 1 afferent input from hindlimb ankle extensor muscles in the cat. 2. Intracellular recordings were obtained from DSCT neurons throughout the rostrocaudal extent of the L3 dorsal root entry zone of the spinal cord. DSCT neurons, physiologically identified as receiving monosynaptic group I input from the ankle extensor muscles, were injected with horseradish peroxidase (HRP) and subsequently reconstructed under the light microscope. 3. In contrast to previous HRP studies of DSCT neurons, these cells were found to have extremely extensive and complex dendritic trees, that often extend beyond the region of Clarke's column. Dendrites were found to extend into the white matter of the dorsal columns, and/or into the spinal gray matter in a ventrolateral direction. The large dendritic spread of DSCT neurons was found to occupy up to 60% or more of the cross-sectional area of Clarke's column. 4. DSCT neurons receiving monosynaptic group I input from the single functional group of ankle extensor muscles were not found to be confined within a specific transverse region of Clarke's column, in contrast to a previous proposal. Instead, these cells could be found throughout Clarke's column. 5. The present results demonstrate that DSCT neurons, physiologically identified as receiving group I muscle afferent input, exhibit dendritic trees that are considerably more extensive and morphologically complex than indicated by previous studies. In addition, the present results do not support a previous proposal of a strict somatotopic arrangement for DSCT neurons and their dendritic envelopes within Clarke's column in the transverse plane. PMID- 2313346 TI - Synchronized discharge of taste neurons recorded simultaneously in rat parabrachial nucleus. AB - 1. Cross-correlation analysis was made in the taste-sensitive neuron pairs recorded simultaneously from the parabrachial nucleus (PBN) of rats. Three indexes were adopted to evaluate the activities of the taste neurons; namely, 1) spike response density (RD value), which is the net spike density to stimulation with the four basic tastes; 2) the frequency of correlated discharges (FC value in spikes per second), which was determined by measuring the area of the peak appearing in the cross-correlogram (CC) during application of the test fluids; and 3) the weight of correlated discharge (WC = FC/RD), which shows the relative importance of correlated discharges in the taste signals delivered by a component neuron of a given pair. 2. In 11 of 23 pairs, the CCs exhibited peaks during stimulation with tastants. These 11 pairs, which were recorded in the pontine taste area, were composed of 18 NaCl-best (most sensitive to NaCl) and 4 HCl-best neurons. In eight pairs, the best-stimulus of both of the component neurons was NaCl, and it was HCl in one pair (homo-type pairs). The remaining two pairs were composed of an NaCl-best and an HCl-best neuron (hetero-type pairs). 3. In eight homo-type pairs (7 NaCl-best pairs and 1 HCl-best pair), each pair exhibited the maximal FC value during stimulation with the best-stimulus of the component neurons (2.3 less than or equal to maximal FC less than or equal to 26.6 Hz). In the remaining three pairs, the maximal FC values were low (0.8-1.9 Hz).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313347 TI - Mormyromast electroreceptor organs and their afferent fibers in mormyrid fish. II. Intra-axonal recordings show initial stages of central processing. AB - 1. Physiologically and morphologically identified primary afferent fibers from mormyromast electroreceptor organs were recorded intracellularly. The fiber recordings were made from the nerve root of the posterior lateral line nerve, where the fibers enter the brain, and from the electrosensory lateral line lobe (ELL), near the central terminals of the fibers. 2. The intracellular recordings reveal a variety of potentials, synaptic and nonsynaptic, in addition to the large orthodromic action potentials from the periphery. The goal of the present study was to describe and interpret these various potentials in mormyromast afferent fibers as a first step in understanding the processing of electrosensory information in ELL. 3. Three types of synaptic potentials were recorded inside mormyromast afferent fibers: 1) electric organ corollary discharge (EOCD) excitatory postsynaptic potentials (EPSPs), driven by the motor command that elicits the electric organ discharge (EOD); 2) EPSPs evoked by electrosensory stimulation of electroreceptors in the skin near the electroreceptor from which the recorded fiber originates or by direct stimulation of an electrosensory nerve; and 3) inhibitory postsynaptic potentials (IPSPs) evoked by electrosensory stimulation of more distant electroreceptors. These synaptic potentials can be attributed to synaptic input to postsynaptic cells in ELL that is observed inside the afferent fibers because of electrical synapses between the fibers and the postsynaptic cells. 4. The peripherally evoked EPSPs could frequently be shown to be unitary. The unitary EPSPs were identical to the orthodromic spikes in originating from a single electroreceptor, in threshold, and in latency shift with increasing stimulus intensity. These similarities suggest that the unitary EPSPs are electrotonic EPSPs caused by impulses in other mormyromast afferent fibers that terminate on some of the same postsynaptic cells as the recorded fiber. The peripherally evoked IPSPs had a longer latency than the EPSPs or orthodromic spikes, requiring the presence of an inhibitory interneuron. 5. The peripherally evoked EPSPs, both unitary and nonunitary, show absolute refractory periods of 3-8 ms, followed by relative refractory periods of approximately 8 ms, when tested with two identical stimuli to a nerve. These refractory periods are interpreted as because of refractoriness in the fine preterminal branches of the axonal arbor. 6. A depolarizing afterpotential is commonly associated with the orthodromic spike and probably results from the successful propagation of the spike into the entire terminal arbor. The depolarizing afterpotential has a refractory period that is similar to that of the peripherally evoked EPSPs and that is also interpreted as refractoriness in the fine preterminal branches.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313348 TI - Mormyromast electroreceptor organs and their afferent fibers in mormyrid fish. III. Physiological differences between two morphological types of fibers. AB - 1. Mormyromast electroreceptor organs in electric fish of the family Mormyridae have two types of separately innervated sensory cells, the A and B sensory cells of Szabo and Wersall. The first paper in this series showed anatomically that afferent fibers from the two types of sensory cell terminate centrally in separate zones of the electrosensory lateral line lobe (ELL), fibers from A cells terminating in the medial zone and fibers from B cells terminating in the dorsolateral zone. The goal of the present study was to determine the physiological differences between the two morphologically distinct types of mormyromast afferent fibers. 2. The present study has two parts. In the first part, mormyromast fibers were recorded near their central terminals in the two mormyromast zones of ELL. In the second part, mormyromast fibers were recorded from a peripheral electrosensory nerve. In both parts, various electrosensory stimuli were delivered and voltage thresholds were measured at the electroreceptor. 3. In the first part of the study, mormyromast fibers terminating in the two central zones were found to be different in their thresholds and in the maximum number of spikes evoked by a single stimulus. Afferent fibers terminating in the medial zone, which arise from A sensory cells, had higher thresholds and smaller maximum spike numbers than fibers terminating in the dorsolateral zone, which arise from B sensory cells. 4. In the second part of the study, the same two groups of fibers--one group with a high threshold and a small maximum spike number, and a second group with a low threshold and a large maximum spike number--were identified in extracellular recordings from a peripheral electrosensory nerve. The thresholds of the two groups were quite distinct, allowing the fibers to be divided into high- and low-threshold groups, which most likely represent the fibers from the A and B sensory cells, respectively. 5. The high- and low-threshold groups of fibers recorded from peripheral nerve were found to be different in a number of additional properties besides threshold and maximum spike number. Additional differences were found in the following properties: strength-duration curve, correlation with a receptor potential recorded at the electroreceptor, tuning curve, and short latency facilitation by a conditioning stimulus. Thus there appear to be several physiological differences between mormyromast afferent fibers from A and B sensory cells, in addition to the differences in threshold and spike number.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313349 TI - Voltage behavior along the irregular dendritic structure of morphologically and physiologically characterized vagal motoneurons in the guinea pig. AB - 1. Intracellular recordings from neurons in the dorsal motor nucleus of the vagus (vagal motoneurons, VMs) obtained in the guinea pig brain stem slice preparation were used for both horseradish peroxidase (HRP) labeling of the neurons and for measurements of their input resistance (RN) and time constant (tau 0). Based on the physiological data and on the morphological reconstruction of the labeled cells, detailed steady-state and compartmental models of VM were built and utilized to estimate the range of membrane resistivity, membrane capacitance, and cytoplasm resistivity values (Rm, Cm, and Ri, respectively) and to explore the integrative properties of these cells. 2. VMs are relatively small cells with a simple dendritic structure. Each cell has an average of 5.3 smooth (nonspiny), short (251 microns) dendrites with a low order (2) of branching. The average soma dendritic surface area of VMs is 9,876 microns 2. 3. Electrically, VMs show remarkably linear membrane properties in the hyperpolarizing direction; they have an average RN of 67 +/- 23 (SD) M omega and a tau 0 of 9.4 +/- 4.1 ms. Several unfavorable experimental conditions precluded the possibility of faithfully recovering ("peeling") the first equalizing time constant (tau 1) and, thereby, of estimating the electrotonic length (Lpeel) of VMs. 4. Reconciling VM morphology with the measured RN and tau 0 through the models, assuming an Ri of 70 omega.cm and a spatially uniform Rm, yielded an Rm estimate of 5,250 omega.cm2 and a Cm of 1.8 microF/cm2. Peeling theoretical transients produced by these models result in an Lpeel of 1.35. Because of marked differences in the length of dendrites within a single cell, this value is larger than the maximal cable length of the dendrites and is twice as long as their average cable length. 5. The morphological and physiological data could be matched indistinguishably well if a possible soma shunt (i.e., Rm, soma less than Rm, dend) was included in the model. Although there is no unique solution for the exact model Rm, a general conclusion regarding the integrative capabilities of VM could be drawn. As long as the model is consistent with the experimental data, the average input resistance at the dendritic terminals (RT) and the steady-state central (AFT--- S) and peripheral (AFS----T) attenuation factors are essentially the same in the different models. With Ri = 70 omega.cm, we calculated RT, AFS----T, and AFT----S to be, on the average, 580 M omega, 1.1, and 13, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313350 TI - Skeletal assessment in neuroblastoma--the pitfalls of iodine-123-MIBG scans. AB - This study was carried out to compare iodine-123 metaiodobenzylguanidine ([I123I]MIBG) and technetium-99m-methylene diphosphonate bone scans (99mTc-MDP) in the detection of skeletal involvement by neuroblastoma. Forty-four children with neuroblastoma underwent both [123I] MIBG and 99mTc-MDP scans within a 4-wk period; bone marrow examination also was performed; all these investigations were done both at diagnosis and at follow-up. At diagnosis, four children with Stage 4 disease had normal [123I]MIBG scans but abnormal 99mTc-MDP scans, while at follow up there were four children with negative [123I]MIBG studies who later died from disseminated neuroblastoma. All eight scans are considered false-negative. In 24 children, the [123I]MIBG revealed more extensive disease with 161 positive sites while the 99mTc-MDP scan showed only 100 positive sites; 34 of these sites were common to both studies. This study shows that underassessment of skeletal involvement by neuroblastoma occurred using [123I]MIBG scans and that one cannot therefore substitute [123I]MIBG for 99mTc-MDP bone scans in the staging of neuroblastoma. PMID- 2313351 TI - FDA approves three imaging agents and considers two other agents and the gastric emptying petition. PMID- 2313352 TI - The controversy about the nuclear medicine investigation of neuroblastoma. PMID- 2313353 TI - Thallium-201 SPECT increases detectability of thyroid cancer metastases. AB - Thallium-201- (201Tl) chloride is known to accumulate in metastatic foci of differentiated thyroid carcinoma, but small and deep-seated lesions are generally not detectable by planar imaging. We have evaluated the use of 201Tl-chloride single-photon emission computed tomography (SPECT) in 41 post-thyroidectomy patients with differentiated thyroid carcinoma and one with medullary carcinoma; planar imaging alone was done in eight additional patients (total 50). Of 20 patients with known metastatic disease, planar 201Tl images were positive in 12 (60%) but SPECT revealed an additional 5 (25%) who had metastases (total 85%). SPECT revealed foci as small as 1.0 cm in the neck and 1.5 cm in the lungs, and was particularly useful in detection of disseminated micronodular pulmonary metastases, especially in patients whose scans were negative with diagnostic doses of 131I. Some pitfalls in interpretation of the tomographic reconstructions were found. Thallium-201 SPECT is a marked improvement over planar imaging in the detection of metastases of differentiated thyroid cancer. PMID- 2313354 TI - Importance of scintigraphic measurements of human splanchnic blood volume. PMID- 2313355 TI - Metabolic fate of [13N]ammonia in human and canine blood. AB - Nitrogen-13- ([13N]) ammonia is a widely used tracer for PET myocardial blood flow studies. Quantification of blood flow using tracer kinetic principles requires accurate determination of [13N]ammonia activity in blood. Since [13N] ammonia is rapidly metabolized, the arterial input function may be contaminated by labeled metabolites. We, therefore, characterized the 13N-labeled metabolites in blood after intravenous (i.v.) injection of 20 mCi [13N]ammonia in nine healthy volunteers. Utilizing a series of ion exchange resins, 13N-labeled compounds were separated into four groups: ammonia, neutral amino acids, acidic amino acids, and urea. Analysis of the metabolic fate of [13N]ammonia indicates that over 90% of the blood activity within the first two minutes after injection is present as [13N]ammonia. However, there is considerable contamination of the blood activity at 3-5 min by [13N]glutamine (amide) and urea, which collectively represent 18%-50% of the blood activity. Thus, correction of the arterial input function for 13N-metabolites is required to accurately quantify the arterial input function of [13N]ammonia in myocardial blood flow studies. PMID- 2313356 TI - A new method for noninvasive quantitation of segmental myocardial wall thickening using technetium-99m 2-methoxy-isobutyl-isonitrile scintigraphy--results in normal subjects. AB - A quantitative index of regional myocardial wall motion obtained from electrocardiogram-gated perfusion images has been assessed. The assumption for the proposed algorithm is that, according to the partial volume effect, the recovery counts by the instrumentation is a function of the object size. Systo diastolic changes in the detected radioactivity would therefore reflect changes in myocardial wall thickness. Ten normal volunteers were studied in control condition by 99mTc 2-methoxy-isobutyl-isonitrile scintigraphy. Electrocardiogram (ECG)-gated images were acquired in multiple projections. End-diastolic and end systolic activity was measured along radii from the center to the edge of the left ventricle. Data are displayed as circumferential profiles and the percent systolic thickening determined according to the formula (end-systolic profile- end-diastolic profile) (end-diastolic profile + background) x 100.) The intra- and interobserver variabilities were +/- 5.4% and +/- 4.1%, respectively. Analysis of regional systolic thickening showed a heterogeneous pattern, with a maximal and minimum value of 35% and 27% located to the infero-apical and to the proximal anterior wall, respectively. Our values correlate well with those reported for normals using cine computed tomography or nuclear magnetic resonance. PMID- 2313357 TI - Experimental test-object study of electronically collimated SPECT. AB - The imaging performance of a prototype electronically collimated single-photon emission computed tomography (SPECT) camera comprising a unique 4 x 4 germanium detector backed by an uncollimated scintillation camera has been evaluated. Three dimensional images of cylindrical test-objects containing either 99mTc (140 keV) or 137Cs (662 keV) are reported. Electronically collimated counts were acquired from the objects rotated to 20 or 40 angular positions in front of the germanium detector to simulate a cylindrical scanning system. For comparison, mechanically collimated data were also acquired from the test-objects. The SPECT images show a slightly better resolution for mechanical over electronical collimation (1.3 +/- 0.25 cm mechanical, 1.5 +/- 0.25 cm electronical at 140 keV; 1.5 +/- 0.25 cm mechanical, 1.7 +/- 0.25 cm electronical at 662 keV). The equi-resolution sensitivity, however, was deduced to be approximately an order of magnitude higher with electronic collimation to image a head-sized object using 99mTc. In addition, the sensitivity gain increases with increasing energy, suggesting the unique potential of electronic collimation in high-energy SPECT. PMID- 2313358 TI - Sex-dependent differences in N-(3-[18F]fluoropropyl)-N-nordiprenorphine biodistribution and metabolism. AB - In our work with the new opioid receptor ligand, N-(3-[18F]fluoropropyl)-N nordiprenorphine, ([18F]FPND), we have noted significant sex-dependent differences in metabolism and distribution. In female rats, metabolism of this ligand proceeds without significant P-450-mediated oxidation of the N-fluoroalkyl side chain, while in male rats, this is the dominant metabolic pathway. In biodistribution experiments, striatal uptake of this ligand is higher in female than in male rats, but no difference in cerebellar uptake is observed. In male rats, no metabolites of [18F]FPND are produced that cross the blood-brain barrier. In contrast, female rats produce a metabolite that both crosses the blood-brain barrier and exhibits opioid receptor-specific binding superior to that of the parent compound. These studies demonstrate that the possibility of sex-dependent metabolism must be considered when the rat is employed to screen new radiopharmaceuticals. PMID- 2313359 TI - Current applications of computers in nuclear medicine. PMID- 2313360 TI - Immunoreactivity affects the biodistribution and tumor targeting of radiolabeled anti-P97 Fab fragment. AB - Hydroxylapatite high performance liquid chromatography was used to prepare two fractions from 125I- Fab 96.5. One fraction (peak 1) had relatively low immunoreactivity (25-38%) and the second fraction (peak 2) had high immunoreactivity (70-81%). Scatchard analysis showed similar affinity constants for the two preparations (2.9 x 10(9) M-1 for peak 1; 3.4 x 10(9) M-1 for peak 2). In biodistribution and imaging studies in athymic mice with human melanoma (FEMX-II) xenografts the high immunoreactivity preparation rapidly cleared from the blood and nontumor organs while retention of radioactivity in the tumor was prolonged. The low immunoreactivity preparation, had slower blood and nontumor organ clearance but faster tumor clearance than the high immunoreactivity fraction. Thus, in these studies highly immunoreactive antibody gave higher tumor to nontumor ratios and enhanced the target to nontarget image contrast. PMID- 2313362 TI - Evaluation of residual myocardial viability in a patient with acute myocardial infarction. PMID- 2313361 TI - Use of isothiocyanatobenzyl-DTPA derivatized monoclonal antimyosin fab for enhanced in vivo target localization. AB - Monoclonal antimyosin Fab (AM-Fab) was radiolabeled with 111In via a new bifunctional chelating agent, isothiocyanatobenzyl-DTPA (SCN-DTPA), and used to visualize acute reperfused experimental myocardial infarction. Antibody localization was compared to 201Tl (0.6 mCi) distribution in nine animals. Each animal was injected intravenously with 0.5 mCi of 111In-SCN-DTPA AM-Fab preparations (Prep 1 [n = 5] and 2 [n = 4]). The biodistribution was compared to that of 111In-labeled conventional bicyclic anhydride DTPA-AM-Fab (n = 5). 111In SCN-DTPA AM-Fab Prep 1 (lowest specific activity) showed highest specific target localization (31.6 +/- 3.5, MEAN infarct[0-20% Tl-201] to normal ration +/- SE) and lowest hepatic sequestration (0.0108 +/- 0.002% ID/g). Prep 2 showed similar infarct localization (18.4 +/- 1.2) to control 111In-DTPA AM-Fab (16.9 +/- 1.1), but had higher hepatic activity (0.0326 +/- 0.014 and 0.0267 +/- 0.006 respectively). This difference in in vivo localization occurred despite the lack of changes in in vitro immunoreactivities of the AM-Fab preparations. The enhanced target localization with minimal hepatic activity may permit a more sensitive diagnostic application of 111In-labeled AM-Fab in future clinical studies. PMID- 2313363 TI - Bone scintigraphy in calcific discitis of childhood. AB - The bone scintigraphic findings of calcific discitis of childhood is described and one new case is presented. A brief review of the value of bone scintigraphy in the diagnosis of this syndrome as well as pathogenesis, clinical course, and treatment is provided. PMID- 2313364 TI - Hepatic uptake of technetium-99m HM-PAO in a fetus. AB - The normal biodistribution of technetium-99m HM-PAO ([99mTc]HM-PAO) includes significant uptake in the brain, liver, and kidneys. A pregnant patient studied with [99mTc] HM-PAO to confirm brain death provided an opportunity to examine the transplacental distribution of this radio-pharmaceutical in the unborn fetus. Uptake in the fetus after transplacental delivery is almost exclusively hepatic with a small amount of biliary excretion. PMID- 2313365 TI - Endotoxin testing with limulus amoebocyte lysate in a radiopharmaceutical containing chelated metallic radionuclides and chelating agents. AB - The gel formation by endotoxin with limulus amoebocyte lysate (LAL) solution requires the presence of free calcium ions. The chelating agents and radiopharmaceuticals prepared from the chelating agents always reduce the available free calcium levels present in the kits used for the testing of apyrogenicity and thus inhibit gel formation of LAL with E. Coli endotoxin (ET). This inhibition of gel formation could be reversed by the addition of excess free calcium ions or the excessive dilution of radiopharmaceuticals and chelating agents. The tests of positive control (0.2 ml ET units and LAL), inhibition control (0.1 ml sample, 0.1 ml ET and LAL), and negative control (0.1 ml sterile saline and LAL) were carried out with the fresh preparation (0.1 ml) of samples (triplicate), tropolone, ACD anticoagulant, and 99mTc-labeled radiopharmaceuticals. In the Ca-supplemented tests, 0.1 ml of 60 mM sterile calcium chloride solution was added to the test solutions and incubated for 60 min at 37 degrees centigrade. The results of gel formation (+ve and -ve) and normalization of inhibition control tests with Ca-supplement indicate that commercial LAL kits need extra calcium ions for the correct testing of the apyrogenicity of chelate-containing radiopharmaceuticals and chelating agents. PMID- 2313366 TI - Penile blood flow by xenon-133 washout. PMID- 2313367 TI - Scintigraphic cholecystokinin-induced bile reflux named as Krishnamurthy-Bobba sign. PMID- 2313368 TI - Negotiating care. AB - The growth of corporate orientation for health care structures, with a focus on bottom-line management, has radically altered the role of nurse executives. With the organizations's emphasis on performance, productivity, and results, successful nurse executives are now integrating the management of the delivery of nursing care with the management of complex corporate structures and relationships. The editor of Executive Development discusses the rapidly changing expectations and demands of the contemporary nurse executive's work. PMID- 2313369 TI - Evaluating an RN/co-worker model. AB - In 1988 the University of Kentucky Hospital implemented a nurse extender model to cope with diminishing RN resources. After a year and a half of operation the model was evaluated in terms of training costs, retention, personnel costs, RN and co-worker satisfaction, and impact on quality of care. The authors conclude that although it has some limitations, the Co-worker Model allowed patient beds to remain open while minimally affecting quality. PMID- 2313370 TI - Care for the underinsured: who should pay? AB - Inner-city medically underinsured adults describe their preferences for health care and willingness to pay for health care services. The responses of 146 patients attest to the burden of administrative and economic responsibility placed on the public health care sector for indigent patient care. The results of this survey address the information required by the nurse managers who must balance patient needs against administrative pressures to generate revenue from patient fees. PMID- 2313371 TI - Using workload analysis and acuity systems to facilitate quality and productivity. AB - Reimbursement, budget, and nurse availability constraints no longer support the quality-at-any-cost concept. However, clear definitions of clinical and satisfaction outcomes, nursing responsibilities that contribute to those outcomes, and reasonable time targets for staff contributions can help nurses at all levels analyze and prioritize work load to build new or update existing acuity systems. The author describes specific methods nurse executives and managers can use to involve and guide staff members in (1) determining realistic and compatible standards of care, performance, and resource productivity, (2) integrating quality-based time standards into acuity systems, and (3) using acuity information to manage delivery of a targeted, desired level of ongoing quality care. PMID- 2313372 TI - Research activities at the Brigham and Women's Hospital. PMID- 2313373 TI - How do nurses use their time? AB - Nurses spend an average of only 31% of their time with patients. The authors determined how nurses spend their time and suggest three ways to reduce time spent on non-essential nursing functions: delegation of some tasks to support personnel, greater use of pharmacy personnel in a decentralized setting, and greater use of computers. Together these changes may both decrease demand for nurses' time and enable professional nurses to focus their energy on tasks that require professional expertise. PMID- 2313375 TI - Nursing image campaign begins. PMID- 2313374 TI - Supply, demand, and salaries. PMID- 2313376 TI - Salaries ease nursing shortage. PMID- 2313377 TI - Implementing salary cost per unit of service productivity standards. AB - Productivity standards based upon labor hours or full-time equivalents were acceptable in the cost-based reimbursement environment of the 1960s and 1970s. In the prospective payment environment of the 1990s, however, they do not enable hospitals to manage their labor expense precisely enough. The author describes an alternative productivity system to measure, report, and manage productive labor expense per unit of service. PMID- 2313378 TI - Modulation of mouse mammary tumor growth and linoleate enhanced metastasis by oleate. AB - This study examines whether oleate may influence the linoleate enhanced metastasis of line 4526 murine mammary tumors. In addition, the in vitro proliferative response of line 4526 to oleate and other selected fatty acids was assessed. Initially, the tumor cells were grown in a defined medium supplemented with palmitate, stearate, oleate, linoleate, linolenate or arachidonate. The unsaturated fatty acids stimulated and the saturated fatty acids inhibited proliferation compared to fatty acid-free medium. Next, we examined the effect of oleate on the linoleate enhanced metastasis of 4526 tumors by substituting oleate for saturated fat in isoenergetic diets containing high or low levels of linoleate. Oleate had no effect on metastasis in mice fed the high linoleate diets but it significantly increased metastasis in mice fed the low linoleate diets. Finally, the fatty acid compositions of tumors and mammary fat pads were compared to diet fatty acid compositions and metastatic frequency. Metastasis corresponded more closely to total unsaturated fatty acids than to total polyunsaturated fatty acids or to any individual fatty acid. These studies suggest that both mono- and polyunsaturated fatty acids may stimulate mammary tumor metastasis. However, the influence of dietary oleate probably depends on the level of linoleate and total unsaturated fatty acids in the diet. PMID- 2313380 TI - Relative folate bioavailability from diets containing human, bovine and goat milk. AB - The present study was designed to determine the relative folate bioavailability from diets containing human, bovine or goat milk and the relative sensitivity of various response criteria used in assessing folate bioavailability. Following a 12-wk depletion period, 16 groups of male rats (n = 5/group) were fed experimental diets with or without 20% milk solids and graded levels of folic acid for 4 wk. Total folates were measured in plasma, erythrocytes, liver and kidney. Bioavailability of dietary folate was determined using slope-ratio statistics. Plasma response was found to be the most sensitive indicator of folate bioavailability based on steepness of slope, goodness of fit (r = 0.96, P less than 0.01) and linearity of response over the entire range of folate intakes. Kidney folate concentration also showed a significant linear relationship to total folate intake (r = 0.69, P less than 0.01). Liver and erythrocyte folate concentrations were not correlated with folate intake (r = 0.33 and r = 0.22, respectively). Using plasma folate as the response criterion, dietary incorporation of human milk significantly enhanced folate bioavailability by 75% (P less than 0.01). With kidney as the response tissue, folate bioavailability from diets containing human and bovine milk was significantly enhanced over milk-free diets. These results show that incorporation of human or bovine milk into diets enhances folate bioavailability and that plasma and kidney folate concentrations are sensitive and specific indicators of folate bioavailability. PMID- 2313379 TI - L-2-oxothiazolidine-4-carboxylate as a cysteine precursor: efficacy for growth and hepatic glutathione synthesis in chicks and rats. AB - Chick and rat experiments were conducted to determine the efficacy of L-2 oxothiazolidine-4-carboxylate (OTC) as a cysteine (Cys) precursor for growth and hepatic glutathione (GSH) biosynthesis. Isosulfurous graded increments of OTC and Cys were added to Cys-free purified amino acid diets that were adequate in methionine. Curvilinear responses to both Cys and OTC for chicks and rats were obtained. Hepatic GSH accumulated in chicks only at dietary Cys levels above 0.10%. In rats, hepatic GSH increased linearly as dietary Cys content increased from deficient to adequate and from adequate to excessive. Utilization of OTC by chicks was as efficacious as isosulfurous levels of Cys for growth and hepatic GSH biosynthesis. In rats, OTC was slightly inferior to Cys for growth and hepatic GSH biosynthesis. Exponential regression slope-ratio growth efficacy values for OTC were 78.5% for chicks and 70.2% for rats; multiple linear regression slope-ratio GSH biosynthesis efficacy values were 80.3% for chicks and 83.7% for rats. It is concluded that orally administered OTC is active as a Cys precursor. PMID- 2313381 TI - Effectiveness of isoascorbate versus ascorbate as an inducer of collagen synthesis in primary avian tendon cells. AB - In contrast to most biologically active molecules, the isomeric form of ascorbate retains significant biological activity. Moreover, in studies in vitro the isomer was found to be an equally effective cofactor in the enzymatic proline hydroxylation reaction. This raises questions about whether the lower biological activity in vivo results from selective transport into the cell, greater instability of the molecule, or stereospecificity by certain enzyme complexes. Distinguishing these possibilities can be accomplished most directly using a cell culture model. In this study primary avian tendon (PAT) cells were used. With PAT cells isoascorbate was shown to be three- to fivefold less active at inducing procollagen production than ascorbate. Isoascorbate was also internalized by the cell at about one-fifth the ascorbate level. In addition, isoascorbate was degraded in the medium at a slightly higher rate (half-life of 1.6 h) than ascorbate (2.1 h). The data are consistent with a model that postulates that once inside the cell isoascorbate is equally effective at inducing procollagen production but selectivity at the transport step restricts the percentage that is actually internalized. In addition, both ascorbate and isoascorbate were found to degrade very quickly inside the cell in the highly oxygenated environment of cell culture (approximately 2 h half-life). When ascorbate was added to the medium (100 micrograms/mL) the level inside the cell quickly reached a maximum (less than 2 h) and declined rapidly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313382 TI - Comparison of the magnitude of the selenite-exchangeable metabolic pool and whole body endogenous selenium in adult rats. AB - The quantitative relationship between the size of the selenite-exchangeable metabolic pool (WSe-EMP) and whole body endogenous selenium (Seend) was investigated in adult male rats. Two experiments based on multiple labeling with stable isotopes were performed. One focused on short-term (7 d, Expt. 1) and the other on long-term (60 d, Expt. 2) relationships. Rats were fed a Torula yeast diet and water supplemented with [76Se]selenite at 0.1 micrograms Se/mL; the in vivo [74Se]selenite tracer was administered orally. Groups of three or four animals were killed at timed intervals and whole carcass or selected organs were analyzed for the stable isotopes 74Se, 77Se and 82Se with hydride generation/inductively coupled plasma mass spectrometry. The value of WSe-EMP was determined from plasma or urine isotope ratios. In Experiment 1, with plasma as the sampling compartment, WSe-EMP at 24 h was 36.5 +/- 1.2% of the baseline value of whole body endogenous selenium (Seend) and 36.3 +/- 1.8% at 7 d. When urine was the sampling compartment, the corresponding values were 3.9 +/- 0.3% and 43.1 +/- 2.8%, respectively. In Experiment 2, WSe-EMP (plasma) was 38.9 +/- 1.3% of Seend at 7 d, increasing to 45.5 +/- 1.6% at 60 d. The corresponding values for urine as the sampling compartment were 45.5 +/- 2.0% (7 d) and 61.5 +/- 1.7% (60 d), respectively. PMID- 2313383 TI - Effect of various dietary factors on the deposition of selenium in the hair and nails of rats. AB - Noninvasive techniques to monitor selenium (Se) status at higher intake levels should be developed if Se supplements are to be given to human subjects as possible anti-cancer agents. Hair and nails have been suggested as indices of Se status because they are easily obtained, transported and stored. However, there has been little research on the potential influence of such factors as dietary Se intake or nutritional status on the levels of Se in hair and nails. Here we report the effects of chemical form of dietary Se and of methionine (Met) status on the Se content of rat hair and nails. Rats were fed diets containing 0.5, 1.5 or 2.5 micrograms/g of Se as sodium selenate (Na2SeO4) or L-selenomethionine (SeMet) for 8 wk. Hair and nail Se retention was two- to threefold greater when dietary SeMet was fed. Hair and nail Se levels increased as liver and muscle Se retention increased in rats fed SeMet, whereas in rats fed Na2SeO4, hair, nails and liver accumulated Se but muscle Se levels remained relatively unchanged. In a second experiment, rats were fed diets containing 0.1, 0.5 or 2.5 micrograms/g of Se as Na2SeO4 or SeMet, +/- added Met (0.3%) for 6 (+Met) or 7 (-Met) wk. Hair and nail Se retention was greater when Met was deficient than when this amino acid was not limiting. These results suggest that factors other than dietary Se intake affect hair and nail Se content and that these tissues should be used with caution for Se status assessment purposes. PMID- 2313384 TI - Comparative toxicity and tissue retention of selenium in methionine-deficient rats fed sodium selenate or L-selenomethionine. AB - Selenium (Se) toxicity is known to be affected by level of intake of the mineral, but there are conflicting reports on the relative toxicities of the various chemical forms of Se. We monitored Se toxicity in rats fed Torula yeast-based diets containing 0.1, 0.5 or 2.5 micrograms Se/g of diet as either sodium selenate (Na2SeO4) or L-selenomethionine (SeMet). Half the diets were supplemented to contain adequate dietary methionine (Met). Weights were monitored weekly for 6 (Met-adequate) or 7 (Met-deficient) wk, at which time the rats were killed. There were no significant differences in final weight among Met-adequate rats, regardless of level or form of dietary Se. Methionine-deficient rats all gained significantly less weight than their Met-adequate counterparts. Selenosis was most severe in the Met-deficient rats fed 2.5 micrograms Se/g of diet as Na2SeO4, as indicated by significantly impaired weight gains. Nonetheless, Se retention in serum, heart, brain, bone, testes, colon, skin, lungs and pancreas was greater in rats fed SeMet than in those fed Na2SeO4, and Met deficiency further intensified this trend. The kidney was the only organ in which Se levels were markedly higher in the severely poisoned Met-deficient rats fed Na2SeO4. Further research is needed to determine whether elevated kidney Se levels are related to the greater toxicity observed in the Met-deficient rats fed Na2SeO4. PMID- 2313385 TI - The effect of chronic alcohol ingestion on free radical defense in the miniature pig. AB - Cellular protection from free radical reactions was measured in hepatic tissue from controls and miniature pigs fed ethanol. The activities of copper-zinc superoxide dismutase (CuZnSOD) and glutathione peroxidase were lower and the activity of manganese superoxide dismutase (MnSOD) was higher in the pigs fed ethanol than in controls. Glutathione concentration was lower in the pigs fed ethanol than in controls. Ethanol consumption did not result in increased lipid peroxidation as assessed by thiobarbituric acid-reactive substances. The ethanol induced effects on the activities of the superoxide dismutases may be a reflection of available metals and/or a response to increased hepatic concentration of oxygen radicals. Because the protection afforded by the glutathione system was altered, pigs fed ethanol may be at risk of peroxidative damage with continued ethanol exposure. PMID- 2313388 TI - Interdisciplinary collaboration in perinatal/neonatal health care. A worthwhile challenge. PMID- 2313387 TI - Dietary polyunsaturated fats uniquely suppress rat liver fatty acid synthase and S14 mRNA content. AB - The objective of these studies was to demonstrate that dietary polyunsaturated, but not saturated, fatty acids decrease mRNA abundance for fatty acid synthase (FAS) and S14. A series of experiments involving adult and weanling rats was designed to examine the ability of saturated (tripalmitin), (n-9) monounsaturated (triolein), (n-6) di-unsaturated (safflower oil), and (n-3) polyenic (fish oil) fatty acids to suppress the gene expression of FAS and S14. Dietary polyunsaturated fats reduced by 75-90% the hepatic abundance of FAS and S14 mRNA. Fish oil, rich in 20- and 22-carbon polyenic fatty acids, was more effective than safflower oil, whereas tripalmitin and triolein were without effect. Polyunsaturated fats were also very effective at preventing the rise in FAS and S14 mRNA associated with weaning. The inhibitory action of polyunsaturated fat was rapidly (less than 3 h) removed by deleting the fat from the meal. Regression analysis revealed a high correlation (0.81-0.94) between FAS and S14 expression among the various dietary studies. These data support the hypothesis that dietary polyunsaturated fats uniquely regulate the gene expression of lipogenic enzymes and that the mediator is likely a specific entity derived from the long-chain polyenic fatty acids. Moreover, the high correlation between FAS and S14 expression supports the hypothesis that S14 is a member of the lipogenic protein family and has potential as a model gene for the study of FAS expression. PMID- 2313386 TI - Nutritional control of rat liver fatty acid synthase and S14 mRNA abundance. AB - The objective of this research was to evaluate the change in abundance of S14 and fatty acid synthase (FAS) mRNAs under a variety of nutritional conditions to evaluate the hypothesis that the regulation of the S14 gene is similar to that of other proteins involved in lipid metabolism and that changes in S14 expression are comparable to those that occur in FAS expression. Livers from rats fed a high carbohydrate diet were found to contain 350- and 100-fold more S14 and FAS mRNA than livers from rats fasted for 48 h. Although feeding a high fat diet increased S14 and FAS mRNA above fasting (P less than 0.05), the level of S14 and FAS mRNAs was only 5% and 4%, respectively, of the amount in the high carbohydrate group. Both S14 and FAS mRNAs accumulated quickly upon intubation of fasted rats with a solution of sucrose. The earliest rise in these mRNAs occurred within 60 min; by 240 min after gavage, each mRNA had increased 30-fold. The rapid induction of FAS and S14 mRNAs was also observed during ingestion of a high glucose meal. Hepatic FAS and S14 mRNA decreased 80-90% and 60%, respectively, during the 21-h interval between meals. This degree of mRNA loss was estimated to require a half-life for FAS and S14 mRNA of less than 8 h and less than 12 h, respectively. Regression analysis of the three dietary studies revealed a correlation coefficient for the relationship between S14 and FAS mRNA abundance ranging between 0.88 and 0.96.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313389 TI - Diminished splenic function in asphyxiated term infants. AB - The effect of birth asphyxia on splenic function has not previously been investigated. We performed quantification of pocked erythrocytes to assess splenic function in 10 term infants with abnormally low Apgar scores and clinical symptoms of birth asphyxia and in 10 healthy term control infants. The mean pocked erythrocyte count of the asphyxiated infants at day 1 (33.9% +/- 6.8 [SD]) was greater than that of the control infants (21.4% +/- 6.3) (P less than .01). By day 3 the mean pocked erythrocyte count of the asphyxiated infants (25.2% +/- 8.4) was still elevated but approaching that of the control infants (18.8% +/- 5.5) (.05 less than P less than .10). In summary, birth asphyxia was associated with an elevation of pocked erythrocytes and decreased splenic function. PMID- 2313390 TI - Indomethacin for patent ductus arteriosus closure. Application of serum concentrations and pharmacodynamics to improve response. AB - Indomethacin dosing for patent ductus arteriosus closure has been standardized despite wide interpatient variability in indomethacin pharmacokinetics. We compared a novel indomethacin dosing approach using individual pharmacokinetic and pharmacodynamic information (group A) with a control group from our institution (group B) and a level 3 university-based intensive care nursery (group C) who were dosed using current dosing guidelines. Permanent patent ductus arteriosus closure was achieved in 27 of 28 (96.4%) group A patients, 10 of 16 (62.5%) group B patients, and 7 of 13 (52.8%) group C patients. Success rates were significantly higher in group A than Groups B and C (P less than .02). Renal toxicity was the only toxicity reported in any group. The major manifestations of renal toxicity, ie, urine output below 1 mL/kg/h or increased serum creatinine by greater than or equal to 0.5 mg/dL, occurred in none of the group A patients but in seven (43.8%) group B and eight (61.5%) group C patients. Renal toxicity was significantly greater in groups B and C than group A (P less than .02). A pharmacodynamic concentration versus response curve was developed and proved predictive of patent ductus arteriosus closure rates in previous studies where indomethacin concentration versus response data were available. Serum concentration monitoring is a valuable adjunct to indomethacin therapy for patent ductus arteriosus closure, especially when a pharmacodynamic approach is used. PMID- 2313391 TI - Infant mortality in Sweden and Finland: implications for the United States. AB - Sweden had the lowest reported infant mortality rate (IMR) among countries of the world from 1920 until 1980. Since 1981, Sweden, Japan, and Finland have shared this number one ranking on a somewhat rotating basis. The United States ranks 18th. In 1985, the reported IMRs in Japan, Sweden, and Finland were 5.5, 6.8, and 6.3, respectively, while that of the United States was 10.6 per 1000 live births. This article presents detailed data on IMR in Sweden, Finland, and the United States. It also includes data on neonatal mortality, postneonatal mortality, age of death, and incidence of low birth-weight in the three countries. The paper briefly describes background information on maternal and infant care in Sweden and Finland, including prenatal care, labor and delivery, sex education, family planning, abortion, infant care, and social benefits in Sweden and Finland. The paper gives possible reasons for the achievement of the low IMR in Sweden and Finland, and considers the implications for the United States. PMID- 2313392 TI - Cytogenetic study of amniotic fluid in the evaluation of fetal death. AB - Cytogenetic study is an important part of the evaluation of intrauterine fetal death. Many tissue cultures fail to grow because of maceration and autolysis of the fetal tissues. We evaluated eight amniotic fluid cytogenetic cultures from patients whose fetus had died. All patients had sonographic evidence of Spalding's sign. In four patients, urea and PGF2 alpha were simultaneously injected into the amniotic cavity. Seven amniotic cultures, gestational age 19 to 33 weeks, grew successfully, even when a tissue culture obtained after delivery failed to grow. One culture, gestational age 36.5 weeks, failed to grow and could not be analyzed. The use of amniotic fluid culture for cytogenetic evaluation of fetal death, obtained at the time of diagnosis, is superior to culture of fetal tissue obtained after delivery. The amniocentesis may also serve for intra amniotic induction of labor. PMID- 2313393 TI - Influence of presentation on neonatal outcome of vaginally delivered low birthweight infants. A matched pair analysis. AB - Neonatal outcome of 30 low birthweight (800 to 2000 g) breech infants delivered vaginally was compared with a matched sample of vaginally delivered vertex infants. Using a multiple regression analysis, presentation was found to be significantly related only to the Apgar score at 1 minute. No effect of presentation was found on Apgar score at 5 minutes, length of stay in the nursery, need for ventilatory support, or incidence of neonatal death, seizures, or intracranial hemorrhage. Thus, vaginal delivery of low birthweight breech fetuses was associated with short-term infant outcomes comparable to those of similar fetuses delivered vaginally from vertex presentations. The findings suggest that prevailing assumptions about the risks of premature breech vaginal delivery need to be evaluated critically. PMID- 2313394 TI - Chorionic chromosome abnormalities and intrauterine growth retardation. AB - Chorion, placental membranes, and embryo all arise from the same fertilized oocyte; therefore, chorionic cells are presumed to reflect fetal chromosome status. Progenitor cells of the embryo are selected from the blastocyst, however, at a very early stage of development. If mitotic nondisjunction were to occur in one of the blastocyst cells destined to become trophoblast, the resultant abnormal cell line would be restricted to extraembryonic tissues. Indeed, chromosome mosaicism confined to the placenta has been found repeatedly in diagnostic chorionic villus sampling, and occasionally in third trimester placentas. Cytogenetically abnormal placental cells are morphologically and perhaps functionally abnormal. Such aberrations might result in deficient oxygen or nutrient supply to the fetus, causing intrauterine growth retardation (IUGR). To investigate this hypothesis we studied chorion and cord blood samples after delivery from 11 confirmed IUGR pregnancies. A minimum of 10 cells were analyzed from each cord blood and chorion specimen (mean number of cells from cord blood = 27; from chorion = 17). None of the cases showed true mosaicism for a hyperdiploid line. We conclude from this preliminary study that few, if any, cases of IUGR are likely to be due to chorionic mosaicism. PMID- 2313395 TI - The role of the lumbar puncture in the admission sepsis evaluation of the premature infant. AB - Premature infants with respiratory distress commonly receive evaluation for sepsis, including a lumbar puncture, within a short time after admission to a neonatal intensive care unit. We questioned the use of the lumbar puncture during the early sepsis evaluation, and since 1979, have omitted this procedure as part of the initial evaluation for sepsis (within 6 hours of birth) of premature infants. We monitored this policy to detect any change in the incidence of meningitis, and now report results accumulated over a 7-year period. From 1979 to 1986, 1390 inborn premature infants of 34 weeks' gestation or less were evaluated for early sepsis within 6 hours of birth. Thirty-two infants (2.3%) were diagnosed with sepsis. Fifteen of these infants died in the first 24 hours of life. Meningitis was not demonstrated by autopsy evaluation. The surviving 17 infants diagnosed with sepsis did not have meningitis. One hundred twenty-three infants whose initial blood cultures were negative developed infection later in their hospital course. Eleven of these 123 infants had infections with perinatally acquired organisms; two had group B streptococcus (GBS) meningitis. Their cases were not compatible with missed meningitis. The remaining 112 infants developed nosocomial infections of which 38.3% developed meningitis without associated bacteremia. These results suggest that the omission of the lumbar puncture in the early sepsis evaluation of the premature infant did not result in any missed meningitis and spared many infants the procedure shortly after birth. The lumbar puncture, however, continues to be vital in the assessment of late infections of the neonate. PMID- 2313396 TI - Community-based perinatal research. AB - A program of clinical perinatal research was established in a community-based hospital in collaboration with private-practice obstetricians and their patients. This longitudinal study, undertaken to investigate the value of a circulating placental protein as an indicator of fetal compromise, enrolled 200 unselected pregnant patients. The project required collection of five blood samples at 16, 20, 24, 28, and 32 weeks' gestation in addition to a level II ultrasound examination at 32 weeks. Baseline and interim prenatal visit data were collected, as were maternal and neonatal data upon delivery. Patients who participated were invariably enthusiastic about their involvement. The physicians and their staff were also generally pleased. We infer from these and other studies a need to provide enhanced educational, participatory opportunities to all pregnant women. We conclude that properly conducted, reasonably funded projects that offer no direct benefit to the patient or physician can be successfully carried out with physicians and their private patients in community hospitals. The potential benefits of developing such extended resources can only enhance medical care and foster satisfaction and cooperation among physicians and patients. PMID- 2313397 TI - Spontaneous pneumothorax in common pulmonary vein atresia. AB - Common pulmonary vein atresia is a rare congenital anomaly that is rapidly fatal unless immediately recognized and corrected by surgical intervention. This article describes three neonates who died with the diagnosis soon after birth. In the constellation of presenting clinical features in each case, the occurrence of early spontaneous pneumothorax was particularly noteworthy. This sign may well be a helpful physiologic marker within the context of suspected congenital heart disease associated with severe pulmonary venous obstruction. PMID- 2313398 TI - Fathers and grieving: coping with infant death. AB - As we have listened to parents who have come to our parent support group during the past 10 years, we have become increasingly aware of the differences in the way fathers and mothers grieve. These differences can lead to misunderstanding and to further hurt and confusion for both parents who are grieving the loss of an infant. Role expectations seem to account for many of these differences. Fathers' responses to infant loss tend to coincide with how they believe they should act as men, rather than how they need to act to confront and resolve grief. We conducted a pilot study of parents' experiences following infant death, and sought more detailed insight from several fathers into their experiences. In this article, we explore some of the differences in the way fathers and mothers grieve and the constraints men experience in resolving grief because of their role expectations. PMID- 2313399 TI - Polemics in perinatology: the abortion thing. PMID- 2313400 TI - Ventilatory management casebook. Acute hypoventilation. PMID- 2313401 TI - Complications of care in a medical intensive care unit. AB - OBJECTIVE: To determine the frequency and nature of complications of care in the medical intensive care unit (MICU). DESIGN: Prospective, observational study. SETTING: Seven-bed MICU in a teaching and referral VA hospital. PATIENTS: 295 consecutive patients admitted to the MICU during a ten-month study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-two patients (14%, 95% confidence interval 13%, 16%) experienced one or more complications during their MICU stays. Compared with other MICU patients, those experiencing complications tended to be older (mean age +/- SD: 63.6 +/- 10.1 years vs 59.3 +/- 14.0 years, p less than 0.02) and more acutely ill (mean Acute Physiology Score +/- SD: 18.3 +/- 8.0 vs 12.5 +/- 8.0, p = 0.0001). These patients also had significantly longer MICU lengths of stay (mean +/- SD: 12.3 +/- 14.7 days vs 3.1 +/- 4 days, p less than 0.0001) and higher hospital mortality rates (67% vs 27%, p less than 0.001). The 67% mortality rate among patients with complications significantly exceeded the expected mortality rate of 46% (calculated from the APACHE risk equation). CONCLUSION: Complications of care in the MICU are not rare and may independently contribute to in-hospital mortality. The potential for complications must be recognized when considering ICU care. PMID- 2313402 TI - Pap tests of rural black women. AB - Cervical cancer is an important cause of cancer mortality in black women. Pap tests may prevent such deaths, but poor, rural black women are relatively less likely than others to be screened. In order to understand why that is so, the authors surveyed 149 women in three rural North Carolina counties. Thirty-three percent of the women interviewed had not had a Pap test in the preceding three years. Variables independently associated with not having a recent Pap test included: having no identifiable source of medical care; having more than one source of gynecologic care; having an internist provide gynecologic care; and perceiving psychological barriers to Pap tests and pelvic examinations. Income, educational level, and health insurance status were not associated with having a recent Pap test. Although access to care remains a problem for some, better use should be made of the medical care encounters available. PMID- 2313403 TI - Racial bias in presentation of cases. AB - To investigate whether medical housestaff report race information differently during case presentations of black patients and white patients, a prospective observational study was performed. Without informing housestaff, a chief resident recorded data during consecutive case presentations over two months. For each presentation, the data included: 1) whether, where, and how often race was identified; 2) whether certain prospectively selected, "possibly unflattering characteristics" were mentioned; and 3) whether any "justifying" diagnoses were considered during presentation or subsequent discussion. Justifying diagnoses were those in which a patient's race was important in considering the likelihood of possible diagnoses. Twenty-three house officers presented 18 black and 35 white patients. A single East Indian patient was excluded from analysis. Race was specified more often during presentations of black than of white patients (16 of 18 for blacks vs. 19 of 36 for whites; p less than 0.01). For two black patients, a justifying diagnosis was considered, but excluding these patients did not change the results. Two other differences did not achieve statistical significance. Race was more often specified prominently and repeatedly during presentations of black patients. Among patients to whom "possibly unflattering" characteristics were attributed, race was more likely to be specified for blacks (10 of 10) than for whites (4 of 9). These case presentations appeared to show a subtle bias. PMID- 2313406 TI - Unified general internal medicine training programs: a path for general medicine. PMID- 2313404 TI - Attitudes of house officers toward the autopsy. AB - STUDY OBJECTIVE: To assess the attitudes of house officers in internal medicine and pathology about the value and use of the autopsy. DESIGN: Self-administered multiple-choice questionnaire. SETTING: Two New York City urban teaching hospitals. SUBJECTS: 112 internal medicine and 37 pathology house officers who were on site during the survey period. MAIN RESULTS: Most internal medicine house officers (86%) felt that the autopsy rate was too low and needed to be increased. The most common reason the residents cited for the low rate was the reluctance of families to grant permission. A majority of medicine housestaff (78%) felt they needed more instruction on how to ask for an autopsy, and 34% had never received feedback from the pathology department on autopsy results. Most pathology residents (94%) felt the autopsy rate was too low; the most common reasons they cited for the low rate were reluctance of clinicians to request permission and clinicians' fears of being sued for malpractice. CONCLUSIONS: House officers in internal medicine and pathology agreed that autopsies should be performed more frequently, and identified problems in obtaining autopsies that should be addressed by educational, organizational, and regulatory strategies. PMID- 2313405 TI - Integrating residency training in geriatrics into existing outpatient curricula. AB - In recent years, the need for increasing the geriatrics component of residency training has been repeatedly addressed; however, there are still many programs that have been unable to meet this need. While alternative sites, such as geriatric evaluation units and nursing homes, may be the ideal sites to teach some aspects of geriatrics, this article argues that the ambulatory care program, required in all residency programs, is the appropriate setting for teaching many of the core skills needed to care for most older adults. Teaching geriatrics in the ambulatory setting, which eliminates the strategic and financial obstacles of developing non-hospital-based sites, can be accomplished with relatively modest additional resources. This article describes the methods used to integrate geriatrics into the ambulatory care component of one internal medicine residency program and the necessary faculty resources as well as the documentation, via chart audit, of the interns' compliance with recommended practice patterns in five categories. With the exception of vaccination status, interns documented 18% or less of possible pieces of information for their patients. While this assessment showed statistically significant improvement in interns' care of older patients after the program intervention, the overall level of performance was still low, underscoring the need for the integration of geriatrics principles in the ambulatory curriculum. PMID- 2313407 TI - Serving several masters: conflicting responsibilities in health services research. PMID- 2313408 TI - Medicine as a vocation--1990. PMID- 2313410 TI - Changing medical education: matching ideals, clinical realities, and financial constraints. PMID- 2313409 TI - Medical technologies: restraint or discretion? PMID- 2313411 TI - Screening sigmoidoscopy and colorectal cancer mortality. PMID- 2313412 TI - Bedside case presentation in the ambulatory setting. PMID- 2313413 TI - Barbiturates and alcohol withdrawal. PMID- 2313414 TI - Total lymphoid irradiation and discordant cardiac xenografts. AB - Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival. PMID- 2313416 TI - Psychiatric distress during stages of the heart transplant protocol. AB - Psychiatric observations are reported on 101 heart transplant candidates (40 of whom had transplantations). Emotional responses were recorded during the evaluation, during the waiting period, perioperatively, at biopsy, during rejection episodes, and before and after discharge. Those phenomena, with the exception of behavioral management problems, were unrelated to initial psychiatric diagnoses; the diagnoses often reflected emotional reaction to cardiac illness. Most distress after evaluation appeared to be related to the protocol rather than to preexisting psychopathology. The stage of the protocol affected the nature of the reactions. Psychiatric assistance aided the adjustment process. PMID- 2313415 TI - Liposomal amphotericin B for treatment of pulmonary aspergillosis in a heart transplant patient. AB - Pulmonary aspergillosis developed in a 52-year-old man 2 months after heart transplantation for ischemic cardiomyopathy. Conventional amphotericin B therapy caused marked deterioration of his already compromised kidney function after only 10% of the projected total dose. Conversion to liposomal encapsulated amphotericin B was associated with reversal of the kidney dysfunction and clearing of the pulmonary infiltrate. It is now 16 months since completion of therapy, and there is no evidence of recurrent infection. PMID- 2313417 TI - Patients receiving quinolones and cyclosporine after heart transplantation. AB - Six patients required fluorinated quinolone therapy for a variety of infections after heart transplantation. In contrast to findings in a previous report, none of the patients showed any evidence of nephrotoxicity or required a significant change in cyclosporine dose during the treatment period. PMID- 2313418 TI - Coronary artery-right ventricular fistula in a heart transplant patient. AB - Routine coronary angiography 2 years after heart transplantation in a 48-year-old patient revealed a fistula from a septal branch of the left anterior descending artery to the right ventricle. This finding was not present at coronary angiography 1 year before. This coronary-ventricular fistula is most probably the result of repeated endomyocardial biopsies. PMID- 2313419 TI - The International Society for Heart Transplantation. Tenth annual meeting and scientific sessions. April 5-7, 1990, Ft. Lauderdale, Florida. Abstracts. PMID- 2313421 TI - Lumbosacral lesions associated with pelvic ring injuries. AB - In pelvic ring injuries, an anterior lesion is usually combined with a lesion of the posterior ring segment. A fracture of the sacrum is the most common type of posterior lesion. Its severity ranges from a stable minimal compression fracture of the ala of the sacrum to a displaced fracture with complete loss of stability. The fracture line commonly involves the first and second sacral foramina, exiting the bone distally through its free border and proximally just lateral to the articular process of S1. This study shows that in a number of cases the proximal fracture line passes through or medial to the articular process of S1. Consequently, displacement of the involved hemipelvis causes no damage to the lumbosacral junction if the fracture line passes lateral to the articular process of S1. However, any displacement of the mobile hemipelvis must injure the lumbosacral junction with the latter fracture pattern if the fracture line passes through or medial to the articular process of S1. We found an injury of the lumbosacral junction in 6% of all of our pelvic ring injuries and in 38% of those with an unstable vertical sacral fracture. One kind of these lesions, the locked dislocation of the L5/S1 joint, was shown to inhibit reduction of a displaced sacral fracture. Furthermore, these lesions may be responsible for some of the lumbosacral pain frequently persisting after pelvic ring injuries. PMID- 2313420 TI - Three-dimensional transfer-function analysis of the tomographic capability of a confocal fluorescence microscope. AB - The three-dimensional optical transfer function of a confocal fluorescence microscope is derived. It has no missing cone and provides tomographic images of the sample. The derivation is based on the dispersion equation of spherical waves and the diffraction limitation by an objective lens. Experimental results are shown to verify the derivation. PMID- 2313422 TI - Intermediate cuneiform fracture-dislocation. AB - A case of intermediate cuneiform fracture-dislocation is presented along with a review of the literature, a description of the anatomy, and a proposed mechanism of injury. PMID- 2313423 TI - Dynamic condylar screw: a new device. PMID- 2313424 TI - Invited commentary following "A Review of Reduction and Internal Fixation of Adult Femoral Neck Fractures in a County Hospital". PMID- 2313425 TI - Luxatio erecta: the inferior glenohumeral dislocation. AB - Luxatio erecta, or inferior glenohumeral dislocation, is a rare shoulder dislocation usually caused by a hyperabduction injury to the arm. We have reviewed the literature consisting of 80 cases of luxatio erecta and also discuss six additional cases that we have treated. The literature shows that either a fracture of the greater tuberosity or a rotator cuff tear was associated with this injury in 80% of patients; 60% of the patients reviewed sustained some degree of neurologic compromise, most commonly to the axillary nerve. These injuries usually resolved; the time for recovery varied from 2 weeks to 1 year. Only 3.3% of the cases demonstrated significant vascular compromise, but this is the highest incidence for any shoulder dislocation. Doppler studies of the affected arm or observation of the patient overnight are recommended because of the potentially disastrous complications of vascular insufficiency. If there is any indication of a vascular problem, immediate arteriogram is indicated. Although usually fairly easily reduced by overhead traction, the lesion is so rare that few physicians are familiar with the technique of reduction. Fluoroscopy was used in our most recent cases and was helpful in obtaining a complete and safe reduction. PMID- 2313426 TI - Management of vascular injuries in displaced supracondylar humerus fractures without arteriography. AB - One hundred forty-three displaced (type III) supracondylar fractures of the humerus in children were treated over a 5.5-year period with 17 (11.9%) having signs of vascular impairment at the time of presentation. Rapid reduction and Kirschner wire stabilization without arteriogram was performed in each case. In three cases in which satisfactory blood supply to the hand was not present after reduction, circulation was restored after exploration of the brachial artery revealed two intimal tears and one arterial entrapment. The remaining 14 patients were normal at follow-up with no late vascular compromise. Based on these findings, we feel prereduction arteriography is not indicated in this injury. PMID- 2313427 TI - Self-administered nitrous oxide for fracture reduction in children in an emergency room setting. AB - Analgesia using a self-administered mixture of 50% nitrous oxide and 50% oxygen (Nitronox) was evaluated prospectively in 22 children undergoing closed reduction of fractures in the emergency room. The majority of these patients underwent reduction of forearm fractures. When the children were asked about pain after the procedures, 12 (60%) recalled no pain, 7 (35%) minimal pain, and 1 (5%) moderate pain. None recalled severe pain. Eleven (52%) of the patients had minimal pain, 8 (38%) had moderate pain, and 2 (10%) had no pain, as judged by an emergency room physician. None had severe pain. There were no complications and the ease of administration was remarkable. We conclude that N2O:O2 in a 50:50 mixture provides very effective, safe analgesia for fracture reduction in the emergency room setting. PMID- 2313428 TI - Management of low velocity gunshot-induced fractures. AB - Bullets fired from civilian weapons are usually of low velocity, resulting in minimal tissue cavitation as compared to high-velocity weapons. A prospective protocol was initiated for patients sustaining a low-velocity gunshot to the extremity resulting in a stable, nonoperative fracture configuration. Treatment consisted of local irrigation and debridement, tetanus prophylaxis as required, a long acting cephalosporin intramuscularly, and splinting or casting of the fractured extremity. Twenty-five patients were managed by this protocol. This patient population was compared to a random retrospective sample of 25 patients with similar ballistic induced fractures and wounds managed by local debridement and 48 h of intravenous antibiotics. One infection occurred in each group, requiring further therapy. We conclude that the patient with a low-velocity gunshot induced fracture can be managed without the use of short-term intravenous antibiotics with no increased risk of infection. PMID- 2313429 TI - Acetabular depression fracture accompanying posterior fracture dislocation of the hip. AB - The acetabular depression fracture is defined as a rotated, impacted, osteocartilaginous fragment of the posteromedial acetabulum that occurs in conjunction with a posterior fracture dislocation of the hip. Displacement of this fracture fragment creates incongruity of the posterior acetabular articular surface and the potential for hip joint instability. A retrospective review of hip dislocations over a 3-year period disclosed 75 posterior fracture dislocations of the hip. A total of 71 hips had computerized tomography (CT) scanning after successful closed reduction of the dislocation. Of the 75 dislocations, 58 were treated with open reduction and internal fixation for reproducible posterior subluxation or redislocation upon clinical examination, non-concentric closed reduction, and/or unacceptable articular fracture displacement. The acetabular depression fracture was identified in 17 cases (23%). A total of 16 were found on preoperative CT scans, and one was discovered at the time of open reduction. Preoperatively, each of these injuries demonstrated posterior instability with hip flexion less than 90 degrees. Treatment consisted of disimpaction of the fragment with elevation to the level of the concentrically reduced femoral head. The fragment was stabilized with packed cancellous bone graft obtained from the greater trochanter. The separate posterior lip fragment was then reduced and internally stabilized to ensure reduction of the acetabular depression fragment. We conclude that this variant of the posterior fracture dislocation of the hip occurs in a significant percentage of these injuries. Preoperative recognition of this fracture may correlate with posterior hip instability, and its presence may be an indication for open reduction and internal fixation of the fracture. Long-term studies of this lesion are still needed. PMID- 2313430 TI - Biomechanics of Ender rods, compression screw, and Zickel nail in the fixation of stable subtrochanteric femur osteotomies. AB - Compression screws, Ender rods, and Zickel nails were evaluated mechanically to determine their resulting stability in the fixation of experimental subtrochanteric femur osteotomies. Twenty-five pairs of human cadaver femurs were used. Experimental osteotomies were created and a random member of each pair was fixed with a compression screw (AMBI system, Richards Mfg. Co). The other member was fixed with either Ender rods or a Zickel nail. The specimens were oriented in a direction to approximate the in vivo position of maximum resultant force on the femur and then subjected to a single progressive load to failure on a materials testing machine. The ultimate strength of fixation with the compression screw was approximately 4.6 times greater than with the Ender rods and 1.8 times greater than that with the Zickel nail. Ender rods and Zickel nails failed primarily in external rotation, whereas the compression screw failed by bone fracturing and varus bending. PMID- 2313431 TI - Femoral fractures secondary to low velocity missiles: treatment with delayed intramedullary fixation. AB - The literature is replete with descriptions of the advantages of intramedullary nailing in the treatment of femoral fractures. However, little has been reported about the use of this method in femoral fractures resulting from gunshot wounds. Often, the amount of bony comminution and retained metal fragments have discouraged attempts at operative intervention. We reviewed our experience with 26 patients who had sustained low velocity gunshot fractures of the femur that were treated operatively with intramedullary fixation. After injury, the patients were stabilized in the emergency room and placed in balanced skeletal traction. They also received local wound care. When the patients recovered from associated injuries and the bullet wounds were healing, a delayed closed intramedullary nailing was performed. Nineteen patients were followed to union. Seventeen had fractures that united at an average of 4.5 months. One patient had a delayed union, and one had a nonunion. There were no deep wound infections and no cases of osteomyelitis. Range of motion was within 10 degree of the unaffected side in all but one patient, and there were neither rotatory nor angular deformities. PMID- 2313432 TI - External fixation of high-energy upper extremity injuries. AB - Forty patients with high-energy upper extremity injuries involving the humerus and forearm bones were treated by primarye external fixation. Concomitant soft tissue or neurovascular injuries were rated by the Gustilo classification, and this rating correlated well with the final results: three fractures were Gustilo type I, two fractures were type II, and 35 were type III (IIIA, nine fractures; IIIB, eight; and IIIC, 18). Immediate external fixation, open wound treatment, delayed bone grafting, and late internal fixation led to good to excellent results in 73%. Complications were either minor (related to the external fixation and included pin loosening, 20%) or significant (osteomyelitis, 3%). PMID- 2313433 TI - External fixation of femoral fractures: experience with 15 cases. AB - We report our experience with external fixation in 15 femoral fractures in 14 patients. Follow-up times ranged from 4 to 56 months. Thirteen patients had multiple injuries. All but two fractures healed. In one patient with a supracondylar fracture, a knee arthrodesis had to be performed. One septic osteomyelitis of the femur led to amputation. The range of active knee joint motion was greater than or equal to 90 degree in 13 knees. Only six knees, however, regained a flexion of greater than or equal to 120 degrees. Pin tract infection occurred in one case and resolved uneventfully after revision and systemic antibiotics. External fixation should not be routinely used for fixation of femoral fractures, but may be considered in multiply injured and critically ill patients or in case of extensive soft tissue injury. PMID- 2313434 TI - The role of Ender rodding in tibial fractures with an intact fibula. AB - Thirty-three patients with tibia fractures and intact fibula were studied to determine the efficacy of Ender rod fixation in preventing a varus deformity of the tibia. Twenty-one patients were treated nonoperatively with five (23.8%) developing a significant varus angulation (greater than five degrees). No varus malunions were noted in those patients treated with Ender rods. Those patients treated with Ender rods and early weight-bearing had a shorter average time to union than those treated nonoperatively. We therefore feel that Ender rod fixation is a viable treatment modality in tibia fractures with an intact fibula. In these fractures the use of Ender rods helps prevent significant varus malunion and allows early weight-bearing, thus permitting early mobilization of the traumatized patient. PMID- 2313435 TI - Indium-111 leukocyte scanning and fracture healing. AB - This study was undertaken to determine the specificity of indium-111 leukocyte scans for osteomyelitis when fractures are present. Midshaft tibial osteotomies were performed in 14 New Zealand white rabbits, seven of which were infected postoperatively with Staphylococcus aureus per Norden's protocol. All 14 rabbits were scanned following injection with 75 microCi of indium 111 at 72 h after osteotomy and at weekly intervals for 4 weeks. Before the rabbits were killed, the fracture sites were cultured to document the presence or absence of infection. The results of all infected osteotomy sites were positive, whereas no positive scans were found in the noninfected osteotomies. We concluded from this study that uncomplicated fracture healing does not result in a positive indium 111 leukocyte scan. PMID- 2313436 TI - A comparison of the mechanical properties of fiberglass cast materials and their clinical relevance. AB - The mechanical properties of five synthetic fiberglass casting materials were evaluated and compared with the properties of plaster of Paris. Two of the tests were designed to bear clinical relevance and the third to determine intrinsic material properties. The effect of water on strength degradation was also evaluated. It was found that the synthetics as a group are far superior to plaster of Paris in all methods of testing and that, among the synthetics, KCast Tack Free, Deltalite "S", and KCast Improved were the stronger materials. Clinically, the most important results are that the synthetics attain their relatively high strength in a much shorter time frame than does plaster of Paris, and retain 70-90% of their strength after being immersed in water and allowed to dry. PMID- 2313437 TI - Bilateral anterior fracture dislocation of the shoulders. AB - A case of bilateral anterior fracture dislocation of the shoulders is reported. Treatment included an open reduction and internal fixation on the right side and a Neer hemiarthroplasty on the left. The probable cause of injury was trauma, although a convulsive episode cannot be ruled out. Bilateral biceps tendon interposition was also seen in this case. PMID- 2313438 TI - Nontraumatic dislocation of the hip following screw/plate fixation for a femoral neck fracture. AB - An unusual case of nontraumatic hip dislocation following screw/plate fixation of a basicervical fracture of the neck of the femur, which is unassociated with sepsis, is reported. PMID- 2313439 TI - Fracture of the medial condyle of the humerus in an elderly patient. AB - Isolated fractures of the medial condyle of the humerus are rare in any age group and have not been previously reported in the elderly. The case of an 82-year-old who sustained such a fracture is reported. The patient was successfully treated by anatomic reduction and rigid internal fixation. Treatment guidelines and relevant literature are reviewed. PMID- 2313440 TI - The "hypocritic" oath. PMID- 2313442 TI - The use of autologous auricular cartilage for temporomandibular joint disc replacement: a preliminary report. AB - The technique of harvesting auricular cartilage and its use in 22 patients (35 joints) is described. Follow-up was from 3 to 24 months. Pain relief was achieved in 90% of the cases. Function was equal or better to the preoperative situation in all cases. PMID- 2313441 TI - Reconstruction of mandibular discontinuity with autogenous iliac bone graft: report of 34 consecutive patients. AB - This article reviews 34 consecutive reconstructions of mandibular discontinuity defects done between 1972 and 1988. All reconstructions were performed secondarily with use of free iliac crest bone grafting. The technique is described, three cases are presented in detail, and results for the entire series are tabulated. These results show a 100% graft incorporation rate along with low overall morbidity. PMID- 2313443 TI - Fixation of mandibular fractures: a comparative analysis of rigid internal fixation and standard fixation techniques. AB - This study used a prospective design to compare standard therapy (closed or open reduction with 4 weeks of maxillomandibular fixation) to rigid internal fixation (RIF) for the treatment of mandibular fractures. Ninety-two patients with 143 fractures were evaluated and treated. There was no statistically significant difference in the treatment results between the two groups, despite a bias in the distribution of study variables that favored the standard therapy. PMID- 2313444 TI - Treatment of oral squamous cell carcinoma with simultaneous chemotherapy and radiation: results and surgical implications. AB - Thirty-seven patients with oral squamous cell carcinoma, many with advanced disease, were treated initially with a protocol using simultaneous intravenous 5 fluorouracil (5-FU) cis-platinum, and radiation. Twenty-two patients (62%) experienced complete remission after one cycle of therapy. Fifteen patients (38%) demonstrated an incomplete response; surgical resection was possible in 14 of these 15 patients. A second cycle of chemoradiotherapy was administered to all 37 patients. After this treatment resection is possible for some patients who are initially inoperable, and surgery is necessary only for those patients (38%) who show an incomplete remission after the first cycle of therapy and for those who present initially with bony invasion. Furthermore, the treatment of cervical nodes and intraoral disease may be divorced and the extent of surgery may be reduced for many patients. A 5-year survival of 76% is predicted for this group of patients. The described protocol shows promise for treatment of oral squamous cell carcinoma. PMID- 2313445 TI - Histochemical analysis of the masseter and temporalis muscles in macaca mulatta after mandibular advancement using rigid or nonrigid fixation. AB - This study compared the histochemical characteristics of the temporalis and masseter muscles in monkeys who underwent mandibular advancement with and without immobilization of the mandible. The results showed, when compared with controls, that the animals who underwent maxillomandibular fixation (MMF) following advancement of the mandible had significant atrophy in both temporalis and masseter muscles. In contrast, much less myoatrophy was noted in the animals who underwent rigid internal fixation and no MMF following advancement of the mandible. PMID- 2313446 TI - Palatal mass of 10 years' duration. PMID- 2313447 TI - A life-threatening epidermoid cyst of the floor of the mouth: report of a case. PMID- 2313448 TI - Adenomatoid odontogenic tumor: report of two cases and survey of 126 cases in Japan. PMID- 2313449 TI - Microembolization and resection of a highly vascular pyogenic granuloma. AB - An unusual case is reported of a hypervascular pyogenic granuloma arising from the mandible which continued to grow postpartum in a person with an associated port-wine nevus. Microembolization of the lesions permitted complete surgical removal with minimal blood loss. This case supports the theory of arteriovenous anastomosis being associated with the pathogenesis of pyogenic granulomas. PMID- 2313450 TI - Erythema infectiosum--the fifth disease: case report. AB - A case of erythema infectiosum (fifth disease) is discussed. As it is a childhood illness that initially presents with a facial rash, the oral and maxillofacial surgeon will often be the first practitioner to diagnose this interesting, but benign, disease. PMID- 2313451 TI - Acquired Brown's syndrome: iatrogenic causes. AB - Two cases of iatrogenic acquired Brown's syndrome are presented, and other causes of this disorder and its treatment are discussed. Care should be taken not to cause damage when operating in the region of the trochlea. PMID- 2313452 TI - Double-layer closure for temporomandibular joint discoplasty. PMID- 2313453 TI - A unified AAOMS. PMID- 2313454 TI - Maintaining dental licensure. PMID- 2313455 TI - The European view of the double degree. PMID- 2313456 TI - Snout suffocation syndrome. PMID- 2313457 TI - Is there a mandate for the double degree? PMID- 2313458 TI - Urokinase administration in pediatric patients with occluded central venous catheters. AB - The effectiveness of urokinase in declotting central venous catheters was retrospectively assessed in a pediatric population of 63 patients ranging in age from 4 days to 22 years (mean, 6.4 years). Results of treatment from 103 episodes of catheter occlusion were evaluated. Urokinase was instilled into occluded single-lumen catheters and into each lumen of double-lumen catheters, as well as into occluded implanted ports. Patency was restored to 101 of 103 occluded catheters, with no side effects observed subsequent to clearance of the catheters with the urokinase infusion. Significant cost savings were seen using urokinase to restore patency as compared to the cost of replacing the catheter. These data clearly support the use of urokinase in a pediatric population as a safe and cost effective alternative to catheter replacement in cases of thrombotic occlusion. PMID- 2313459 TI - Antineoplastic vesicant extravasation. AB - The administration of antineoplastic drugs is an almost-daily responsibility of the I.V. nurse, and the possibility of extravasation is ever-present. The nurse's thorough knowledge of these drugs, including their actions, side effects, and the appropriate interventions in the event of an extravasation, is essential to providing optimal I.V. care to patients. This article is based on the extravasation management policies and procedures of Spartanburg Regional Medical Center, Spartanburg, S.C. PMID- 2313460 TI - A creative approach to comprehensive i.v. therapy documentation. AB - Specific, thorough documentation is required to provide continuity of care to patients receiving intravenous therapy. In addition, though the Joint Commission on Accreditation of Healthcare Organizations' regulations require documentation of patient teaching and patient response to treatment, this information is frequently omitted from I.V. therapy records. A checklist was devised to provide a systematic, comprehensive method of documenting I.V. therapy procedures. PMID- 2313461 TI - Continuous subcutaneous infusion of narcotics. AB - Many cancer patients will experience pain. However, this pain can be controlled through the appropriate administration of narcotics. While narcotics can be taken orally and titrated to achieve a level of patient comfort, complications or the progression of disease may prohibit the use of oral analgesics. Continuous subcutaneous infusion of narcotics represents an alternate approach to pain management which can be effective in the management of cancer pain. PMID- 2313462 TI - Intravenous infusion by superficial vein in the neonate. AB - State-of-the-art equipment, such as extremly-low-volume controlled infusion pumps and Teflon catheters, has simplified the management of intravenous therapy in the newborn. This article details the proper I.V. insertion procedure for neonates. It also reviews indications for neonatal infusion, preferred insertion sites, types of catheters currently in use, and potential complications relevant to neonatal intravenous care. PMID- 2313463 TI - Evaluation of the SURECATH access device. PMID- 2313464 TI - The Third Workshop on Stress-Related Diseases and Immunity: Psychoimmunology. PMID- 2313465 TI - Evaluation of the ELISA test for detection of Entamoeba histolytica in feces. AB - The clinical utility of an ELISA test with monoclonal antibodies to detect antigen of Entamoeba histolytica in feces was evaluated in 150 patients with gastrointestinal symptoms. Each subject was examined by rectosigmoidoscopy with rectal smear and/or a triple stool search for ova-bacteria-parasite (OBP); in addition, one stool sample was collected for the ELISA test. All the tests were independent and double blind. E. histolytica was detected by OBP and/or rectosigmoidoscopy in 66 patients; 61 patients had other parasites; and in 23, no parasites were identified. Of all patients, 116 were positive for the ELISA test. Of these, E. histolytica was identified in 52. In 47, other parasites were identified and in 17, no parasites were found. The ELISA test with a monoclonal antibody against E. histolytica antigen showed higher sensitivity than the standard diagnostic methods: the ability to detect the presence of E. histolytica antigen regardless of the destruction of the parasite or of the error due to misidentification of the parasite resulting from faulty preparation of the samples. PMID- 2313466 TI - Cerebrospinal fluid corticotropin-releasing factor levels and stimulation test in dementia of the Alzheimer type. AB - Experimental findings have recently suggested a toxic role for glucocorticoids in hippocampus, the main brain target for the adrenocortical hormones. In this study, we explored the activity of the hypothalamus-pituitary-adrenal (HPA) axis in a group of patients with dementia of the Alzheimer's type (DAT) and in a control group of age-matched subjects. We measured the corticotropin-releasing factor (CRF) levels in cerebrospinal fluid (CSF) and evaluated the plasma cortisol response to a CRF stimulation test. While no differences were observed in the results of the CRF test for two groups, CSF CRF values in DAT patients were found to be significantly higher than in controls. Bearing in mind the bidirectional relationships between the neuroendocrine and immune systems and the changes in some immunological parameters reported in DAT, the possible role of HPA axis hyperactivity in the pathogenesis of primary dementia is discussed. PMID- 2313467 TI - Functional interactions between interleukin-4, interleukin-2, and tumor necrosis factor-alpha for lymphokine-activated killer cell generation. AB - The purpose of the present study was to explore the interaction between interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF) on the differentiation of human large granular lymphocytes (LGL) into lymphokine activated killer cells (LAK). The data show that recombinant human IL-4 (100 1,000/ml) was able to induce the differentiation of human LGL into LAK effectors. The levels of the IL-4-induced cytotoxicity are significantly lower than those observed after stimulation of LGL by optimal doses of IL-2. This LAK activity generation by IL-4 was not associated with LGL proliferation. When TNF was added in LGL culture in the presence of suboptimal concentrations of IL-4, the lytic capacity of the activated killer cells was significantly enhanced, suggesting an apparent synergy between these two factors. Most interestingly, our data indicate that exogenous TNF can partially overcome the known inhibitory effect of IL-4 on IL-2-induced LGL differentiation into LAK effectors. These findings suggest a role for TNF in the process of LAK induction. PMID- 2313468 TI - Impairment of jacalin binding to serum IgA in IgA nephropathy. AB - A test was set up to analyze the direct binding of serum IgA to the lectin jacalin. Under the testing conditions, jacalin bound to both IgA subclasses and reacted similarly with monomeric and polymeric IgA. A jacalin index was defined to quantify serum IgA binding to this lectin. The jacalin index appeared significantly lower in IgA nephropathy than in controls. This may be related to abnormal IgA glycosylation, which could explain, at least in part, the mesangial deposition responsible for the renal disease. PMID- 2313469 TI - Evaluation of the Beckman Synchron CX4 clinical chemistry analyzer in a hospital laboratory. AB - The Beckman Synchron CX4 random-access multianalyzer was evaluated in a medium sized hospital laboratory. The instrument does end-point, rate, and multipoint assays and carries on-board reagents for 24 tests. In addition to predefined tests, the instrument can be programmed for 100 user-defined tests; these are stored on the hard disk and can utilize up to three component reagents each. The throughput is 200 tests per hour. There is stat testing capability. In our evaluation, within-run and between-run precision and linearity were good, and no reagent carryover was detected. There was good correlation with the in-house methodology for the 19 tests evaluated. A disadvantage at the time of evaluation was interference by elevated bilirubin on creatinine, phosphorus, uric acid, and triglycerides. This problem of interference is being addressed by the manufacturer. PMID- 2313470 TI - An enzyme-linked immunosorbent assay for the detection of antitetanus toxoid antibody using aluminum-absorbed coating antigen. AB - An enzyme-linked immunosorbent assay (ELISA) for the detection of antitetanus antibodies was developed using aluminum-absorbed tetanus toxoid as the coating antigen. The assay was tested by measuring antitetanus antibody levels in serum obtained from subjects before and after immunization with the aluminum-absorbed tetanus suspension. The specificity of the antibodies for tetanus antigen was tested both before and after antitetanus activity was removed with tetanus antigen-coated beads. Also, the activities of the sera were compared with those of a commercially available test. Our results indicated that the aluminum absorbed tetanus suspension can be coated onto standard polystyrene ELISA plates and used to measure antibody titers to tetanus toxoid. PMID- 2313471 TI - Soluble interleukin-2 receptor: elevated levels in serum and synovial fluid of patients with rheumatoid arthritis. AB - Soluble interleukin-2 receptor (sIL-2R) levels were quantitated in the serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and degenerative joint disease (DJD). A sandwich immunoassay, employing two monoclonal antibodies against distinct epitopes on the IL-2R, was utilized for measurement. We found a striking elevation of sIL-2R in RA SF as compared with DJD SF (RA, 1319 +/- 135; DJD, 416 +/- 59; p less than 0.001). RA serum sIL-2R levels were also significantly elevated over DJD levels. There was no interaction between rheumatoid factor (RF) and sIL-2R. RA patients with elevated sIL-2R levels had significantly longer disease duration, higher c-reactive protein (CRP) levels in serum and SF, and higher RF levels in serum and SF. The groups were similar in regard to other laboratory variables. The presence of elevated levels of sIL-2R in RA serum and SF confirms the presence of a heightened immune reactivity and in vivo activation of lymphocytes in RA. PMID- 2313472 TI - Detection of antibodies against avian antigens in bronchoalveolar lavage from patients with pigeon breeder's disease: usefulness of enzyme-linked immunosorbent assay and enzyme immunotransfer blotting. AB - The study reported here evaluated the usefulness of the enzyme-linked immunosorbent assay (ELISA) in the detection of antibodies against pigeon antigens in the serum and bronchoalveolar lavage (BAL) of patients with clinical, radiological, and functional evidence of interstitial lung disease (ILD) with and without pigeon breeder's disease (PBD). The results were compared with those obtained by the simultaneous use of counterimmunoelectrophoresis (CIE) in the same patients. In PBD, ELISA detected antibodies against pigeon's sera in both serum and BAL in 100% of patients, while CIE failed to detect the antibodies in the serum of one patient and in most of the samples of BAL. In addition, we used enzyme immunotransfer blotting to determine the number of epitopes in pigeon serum recognized by antibodies present in serum and BAL. There was a heterogeneous response in both fluids, but the reaction pattern demonstrated that patient's sera recognize to-25 different pigeon epitopes. We conclude that ELISA is a highly sensitive and specific method for the detection of antibodies against pigeon antigens in the serum and BAL of patients with PBD and that the host response involves a great number of avian antigens. PMID- 2313473 TI - A new quantitative nitroblue tetrazolium reduction assay based on kinetic colorimetry. AB - A new method for the quantitative assay of nitroblue tetrazolium (NBT) in which the reduction is measured by kinetic colorimetric analysis is reported. The assay is conducted along standard conditions as far as neutrophil isolation and stimulation, except that the test is performed on microtiter plates and the change of color corresponding to NBT reduction is monitored on a kinetic enzyme immunoassay (EIA) reader for 25 min at 490 nm. The results are expressed as mOD/min/in. The influence of several parameters on the results of the assay was studied, including cell concentration, the nature and concentration of the stimulus, and the freshness of the reagents. Cell concentrations of 5 x 10(6) and 1 x 10(7)/ml were found to be optimal, and IgG-coated immunobeads, at a concentration of 1 mg/ml, were found to be the ideal stimuli. NBT reduction for nine normal volunteers studied at 5 x 10(6) cells/ml ranged from 1.80 to 7.30 mOD/min (mean +/- SD = 3.66 +/- 1.69). NBT reduction values at 1 x 10(7) cells/ml in six normal individuals ranged from 2.59 to 7.41 (4.73 +/- 1.89). In contrast, NBT reduction in a child with clinical symptoms suggestive of chronic granulomatous disease was 0.31 mOD/min. This method is considerably simpler than any alternative method for the performance of quantitative NBT assays. PMID- 2313474 TI - Antibodies to the metacestode of Taenia solium in the saliva from patients with neurocysticercosis. AB - IgG antibodies to antigens of Taenia solium metacestodes were detected in saliva samples from patients with intracerebral cysticercosis by means of an enzyme linked immunosorbent assay (ELISA). When compared for IgG antibody activity, saliva samples from patients with various nonparasitic neurological disorders and from clinically healthy individuals yielded significantly lower (p less than 0.001) absorbance values than saliva samples from patients with neurocysticercosis. However, no differences were observed in IgA anti-T. solium activity between patients with neurocysticercosis and controls. These results indicate that the detection of anticysticercus IgG antibodies in saliva by means of ELISA may be of value in the diagnosis of neurocysticercosis. Moreover, collection of saliva provides a noninvasive sampling method for immunoepidemiological surveys on this disease. PMID- 2313475 TI - Elevated levels of circulating immune complexes in human immunodeficiency virus infection. AB - Circulating immune complexes were quantitated in asymptomatic intravenous drug abusers (IVDA), male homosexuals, and patients with lymphadenopathy or acquired immunodeficiency syndrome (AIDS) by two different methods. Circulating immune complexes were elevated in HIV-seronegative IVDAs and male homosexuals, probably reflecting viral infections such as cytomegalovirus (CMV). Circulating immune complexes were also elevated in HIV-seropositive IVDAs and male homosexuals and in patients with lymphadenopathy or AIDS, reflecting infections such as CMV and HIV. PMID- 2313476 TI - Failure of orthoclone OKT3 retreatment in a pancreas transplant recipient with antimurine antibodies. AB - Orthoclone OKT3 is a murine monoclonal antibody that blocks the generation and function of T lymphocytes. It has been shown to be effective in reversing acute cellular rejection in solid organ transplants. However, potential development of antimurine antibodies restricts the duration that the drug can be used and the ability to reuse the drug. The case reported in this article illustrates the failure of retreatment with OKT3 when high titer (1:3200) antimurine antibodies are present. Lack of efficacy of the drug was documented by virtually undetectable circulating OKT3 levels in plasma, no decrease in T3 lymphocytes, and organ rejection. OKT3 should only be reused when immune monitoring (antimurine antibody status, lymphocyte subsets, and OKT3 plasma levels) is performed before, during, and after its use. Patients with high-titer anti-OKT3 antibody should not be retreated with OKT3. PMID- 2313478 TI - Is rheumatoid arthritis really a consequence of benign T cell neoplasia? PMID- 2313477 TI - Calgranulin expression and association with the keratinocyte cytoskeleton. AB - The molecules calgranulin A and B are two intracellular calcium-binding proteins which are expressed by the lesional keratinocytes of inflammatory dermatoses. We have investigated the induction of the calgranulin proteins in an in vitro system and characterized the epidermal form of calgranulin. Using calgranulin-specific monoclonal antibodies, we have shown that these proteins are expressed within the epidermis of skin explants after 12-24 h culture in vitro. The induction of calgranulin-specific staining on culture was prevented, however, by the inclusion of cycloheximide in the culture medium, in sufficient quantities to prevent de novo protein synthesis. Indirect immunofluorescence staining was used to analyse the subcellular localization of the calgranulin proteins. The specific staining pattern with antibodies which recognize the individual calgranulin proteins was retained in detergent insoluble cytoskeletal preparations of epidermis. In Western blotting experiments epidermal calgranulins could be solubilized only by using a urea-based protein extraction buffer. After sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the epidermal extracts a single antigen, with a molecular weight of 13.0 kD was detected with the calgranulin-specific antibody MAC 387. The expression of calgranulins, similar to other members of the same protein family, may regulate cytoskeletal changes in skin disease. PMID- 2313479 TI - Morphometric evaluation of intracytoplasmic lipid in normal and pathological parathyroid glands. AB - The chief morphological criterion for classifying parathyroid glands as 'normal', 'suppressed', or 'activated' is the lipid content of the cytoplasm. In particular, cytoplasm lipid deposit is scanty in the active parathyroid cell, according to many authors. In this paper we present the results of a morphometrical study of ten normal parathyroid glands from patients undergoing thyroidectomy, 20 enlarged 'adenomatous' glands from patients with primary hyperparathyroidism, and 20 glands of normal size from the same hyperparathyroid patients. We aimed at assessing the content of intracytoplasmic lipid of secretory cells in all these conditions. The results show that secretory cells of adenomatous glands have less lipid than those from normal glands; however, there was considerable overlapping of the data in the two groups. The mean lipid content of cells in glands of normal size taken from hyperparathyroid patients was not significantly different from the mean value of normal cells, even when ultrastructural evidence of activation was present in the former. These data suggest that caution has to be exercised in assessing the functional status of parathyroid glands on the basis of lipid content of secretory cells, mainly when differentiating between adenoma and hyperplasia. PMID- 2313480 TI - Colorectal polyps in an Australian population. A histological and immunohistochemical study. AB - The histology and immunohistochemistry of 896 polyps and other focal epithelial abnormalities detected macroscopically in 86 surgical resections from patients with colorectal adenocarcinoma and benign bowel disorders were studied. The lesions identified included 177 adenomas, 387 hyperplastic (metaplastic) polyps, and 202 non-neoplastic polyps designated 'focal cryptal hyperplasia'. Numbers of both neoplastic and non-neoplastic polyps were significantly increased in resections for carcinoma, with 72 per cent of all polyps in right and 10 per cent in left hemicolectomy specimens being neoplastic. Thirty per cent of adenomas were less than 2 mm in diameter and 6 per cent larger than 10 mm. Observations on polyp size, number, distribution, histological appearance, and antigenic composition suggested that focal cryptal hyperplasia evolves into the hyperplastic polyp. In doing so, there is loss of expression of a tissue specific antigen. Hyperplastic polyps were significantly larger in colons with adenoma than in those without. PMID- 2313482 TI - Extragonadal teratocarcinoma derived from embryonal stem cells in chimaeric mice. AB - Three tumours which arose in two (one male and one hermaphrodite) out of 63 chimaeric mice resulting from injection of E14TG2a embryo stem (ES) cells into host blastocysts have been investigated. All of the tumours appeared within the first 3 weeks after birth. The tumour in the male chimaera and one of the tumours in the hermaphrodite were in the perigenital region but were extragonadal. The third, smaller tumour in the hermaphrodite was on the caecum. The perigenital tumour in the male chimaera was a teratocarcinoma with a wide variety of differentiated tissues, including non-pigmented retina, as well as nests of undifferentiated embryonal carcinoma (EC) cells with high levels of alkaline phosphatase activity. The perigenital tumour in the hermaphrodite was a teratoma, less differentiated and with no evidence of EC cells. Glucose phosphate isomerase isozyme analysis indicated that both perigenital tumours were predominantly of the injected ES cell rather than the host blastocyst type. The possible origins of these tumours, which are the first reported to have arisen from ES cells in chimaeric mice, are discussed. PMID- 2313481 TI - Factors producing bile infarction and bile duct proliferation in biliary obstruction. AB - To clarify the factors producing bile infarction and bile duct proliferation in obstructive jaundice, the incidence of the hepatic lesions and the serum levels of the bile constituents were examined in three rat models. (1) Ligation of the common bile duct induced bile infarction, bile duct proliferation, retention of bile in the liver, and elevation of the serum levels of total bilirubin and total bile acids. (2) The rats treated by choledochotomy had bile in the abdominal cavity, but there was no retention of bile in the liver. The degree of development of bile infarction was similar to that of the common bile duct ligation group, but bile duct proliferation was not found: the serum levels of total bilirubin and total bile acids were elevated. (3) In the rats subjected to partial bile duct ligation, bile infarction and bile duct proliferation were seen only in the lobes with ligation of the hepatic ducts: only slight or no elevation of the serum levels of total bilirubin and total bile acids was found. These data suggest that bile infarction is caused by the toxic action of bile constituents other than bilirubin and bile acids, absorbed into the blood from the obstructed biliary system, and that bile duct proliferation is due to mechanical factors following bile retention or direct actions of retained bile in the liver. PMID- 2313483 TI - Anomalous phenotype of cutaneous T-cell infiltrates. PMID- 2313484 TI - How do we teach pathology? Pathology teaching at King's College School of Medicine, London. PMID- 2313485 TI - Resolving LAL Test interferences. AB - A greater understanding of the nature of LAL-Test interferences and the use of permissible dilution have minimized inhibition problems. Common interference mechanisms include suboptimal pH, endotoxin aggregation or adsorption, container effects, unbalanced cation concentration, enzyme or protein modification, and non specific LAL activation. Dilution is the best approach to resolving interferences because over 90% are concentration dependent and are solved by the 1:40 dilution with LAL Reagent Water. Other problems are approached by using dilution plus a specific pretreatment procedure designed to neutralize the offending mechanism. PMID- 2313486 TI - Understanding and setting endotoxin limits. AB - From time to time, biotechnology and other parenteral drug companies must validate LAL pyrogen tests for raw materials or new drug entities. Since there usually are no established endotoxin limits for these items, quality control personnel must be prepared to determine, and defend, pass/fail LAL pyrogen test limits for these articles. An explanation of the FDA/USP approach to setting endotoxin limits is given, and suggestions are made for devising appropriate in house LAL test limits for new drug raw materials and finished products. PMID- 2313487 TI - Variability in the LAL test. PMID- 2313488 TI - A model for the effect of real leaks on the transport of microorganisms into a vacuum freeze-dryer. AB - This paper proposes a model for determining the effect that real leaks, whose flow is viscous in nature, could have on the microorganism density in a vacuum freeze-dryer during a drying process. The model considers the entry of microorganisms to result from real leaks stemming from an environment containing a known bioburden. A means for determining the relationship between the rate of pressure rise of the system (ROR) and the density of microorganisms in a system, stemming from an environment of a known bioburden, is examined. The model also considers the change in the bioburden of the dryer with respect to variations in the primary and secondary drying process. PMID- 2313489 TI - FDA regulations and guidelines. PMID- 2313490 TI - Stability studies of hydralazine hydrochloride in aqueous solutions. AB - The hydrolysis kinetics of hydralazine hydrochloride was studied at pH 1 to 12 at 35 degrees, 50 degrees, and 70 degrees C. The hydrolysis takes place by water attack on the dicationic and the cationic forms of the drug. In addition there is hydroxyl attack on the cationic and the neutral forms of the drug. The drug is not subject to attack by acetate and carbonate buffers, but its decomposition is catalyzed by HPO4 = of the H2PO4-, HPO4 = buffer system. The hydrolysis rate follows first order kinetics under nitrogen, at constant pH, temperature, and buffer concentration. The pH profile indicates that hydralazine has maximum stability near pH 3.5. The drug decomposes to phthalazine and other products. The Arrhenius activation energy was found to be 17.9 kcal/mol at pH 3.5 and the time required for 10% loss (t0.9) was estimated from the Arrhenius parameters to be 1.56 years at 25 degrees C. PMID- 2313491 TI - Highlights of Good Manufacturing Practice in Japan. AB - Good Manufacturing Practice (GMP) in the pharmaceutical industry originated in the United States. Japan, having absorbed many things from the U.S., is actively seeking to establish Good Manufacturing Practice to match the pharmaceutical manufacturing climate in Japan. Several of the themes which highlight Japanese GMP efforts are presented below. PMID- 2313492 TI - Current practices in endotoxin and pyrogen testing in biotechnology. The Quality Assurance/Quality Control Task Group. Parenteral Drug Association. AB - This article presents the results of a nationwide survey of the biotechnology industry regarding endotoxin and pyrogen testing and control. It identifies procedures and methods being used by biotechnology companies, and firms working with biotechnology products, in the testing for and detection of endotoxin and other pyrogenic substances. The review attempts to identify areas of commonality and standardization within the industry and includes topics for discussion at the end of the survey results. PMID- 2313493 TI - Cardiac contusion in pediatric patients with blunt thoracic trauma. AB - To investigate the prevalence of myocardial contusion associated with blunt chest trauma in the pediatric age group, all patients admitted to our institution during a 6-month period with blunt thoracic trauma severe enough to produce a pulmonary contusion or rib fracture were prospectively evaluated. Cardiac evaluation was undertaken, including a multiple-gated acquisition (MUGA) cardiac scan, serial electrocardiograms (ECG), and serum creatine phosphokinase (CPK) and CPK isoenzymes. Seven patients, ranging in age from 2 1/2 to 18 years, with rib fractures or pulmonary contusion by chest roentgenograph were identified. One patient was injured as a passenger in a motor vehicle accident, five were struck by automobiles as pedestrians, and one sustained traumatic asphyxia when a car, supported by a jack, fell on his chest. All had at least one other major organ system injured. All patients had pulmonary contusions as determined by chest radiograph, and two had associated rib fractures. In 43% (three of seven) of patients, a significant cardiac contusion was identified, defined by abnormal right or left ventricular wall motion and a decreased ejection fraction on MUGA scan, and confirmed by an increase in cardiac enzymes and isoenzymes. However, in contrast with adults, no patients had ECG abnormalities. This limited series suggests that cardiac contusion may occur frequently in pediatric patients who have suffered from blunt thoracic trauma significant enough to result in pulmonary contusion. An MUGA scan provides a rapid, noninvasive assessment of cardiac damage in this setting. Further studies will be required to determine the clinical significance and long-term consequences of traumatic myocardial damage in the pediatric population. PMID- 2313494 TI - Deviated trachea in hypoplasia and aplasia of the right lung: airway obstruction and its release by aortopexy. AB - Three cases of male infants with hypoplasia and aplasia of the right lung and dextrocardia are reported. The infants developed increasing obstructive respiratory distress in the first 4 months of life. In all three cases, there was an opaque right hemithorax with overinflation of the left lung, a posterior deviation of the trachea with pulsatile stenosis, and a posteriorly located aortic arch. Hypoplasia (two cases) or aplasia (one case) of the right pulmonary artery and an absence or a remnant of the right main bronchus were also observed. Associated malformations were esophageal atresia with an abnormal high pouch of the proximal esophagus in case 1, and hypertelorismus syndrome in case 2. Because of severe respiratory distress in all three patients, an aortopexy was performed at the ages of 5 months (one infant) and 10 months (two infants). The obstructive respiratory signs disappeared postoperatively in the following weeks. It has been observed that tracheal stenosis in aplasia or hypoplasia of the right lung may be caused by the dislocated aortic arch. An aortopexy can release the airway compression in such cases. Because of associated malformations, a careful evaluation of the airway and vessels is recommended. PMID- 2313495 TI - Dermoid cyst of the scalp: intracranial extension. AB - Intracranial dermoids are rare and are usually associated with cutaneous scalp lesions. Five hundred forty-two scalp lesions were treated in a 22-year period, and were associated with intracranial lesions in three cases. High-risk cases can be identified by clinical and radiological features, confirmed by a computed tomography scan, and then referred for neurosurgical treatment. PMID- 2313496 TI - Glass shrapnel injuries to children resulting from "dry ice bomb" explosions: a report of three cases. AB - Glass shrapnel from explosions of "dry ice bombs," created by thrusting dry ice into glass soft-drink bottles and occluding the opening of the bottles, has produced serious and multiple lacerating injuries in three children, which required major operative intervention. We found no previous reports of this grave hazard. PMID- 2313497 TI - Clinical features of abdominal painful crisis in sickle cell anemia. AB - A retrospective review of children having sickle cell anemia and abdominal painful crisis (APC) was performed in order to delineate the pattern of their presenting clinical characteristics. Of 43 children accounting for 106 cases of APC that occurred during a 4-year period, 94 cases involved a child who had had a previous episode of APC. Symptoms included vomiting (10) and concomitant bone or joint pain (42). Physical findings showed 98 children with normoactive bowel sounds, 96 with a nonrigid abdomen to palpation, two with involuntary guarding, and two with rebound tenderness. Certain clinical characteristics are useful in distinguishing children with sickle cell anemia and APC. As compared with traditional findings that suggest a "surgical" abdomen, most of the children who have sickle cell APC do not experience vomiting, and present with normoactive bowel sounds, nonrigid abdomen, and absence of involuntary guarding or rebound tenderness. Children having presumed APC who receive analgesic medication in an outpatient setting with symptomatic improvement should be hospitalized for observation to monitor for recurrence/progression of symptoms indicative of an abdominal disease process requiring surgery. PMID- 2313498 TI - Bile duct patterns in the hilar region of the liver in two cases of biliary atresia. AB - Bile duct patterns in the hilar region of the liver were demonstrated in two autopsy cases of biliary atresia by three-dimensional graphic reconstructions. In one case, jaundice had completely disappeared after successful hepatic portojejunostomy. However, at the age of 4 months, this patient died of cardiac failure caused by endocardial cushion defect. The histological reconstruction of this case showed that there were large patent bile ducts, 150 microns to 400 microns in diameter, and plenty of bile ductules surrounding the large ducts to form networks. The other patient died of hepatic failure at the age of 9 months. In this case, only a few large ducts ended in bile lakes that did not connect with the portojejunostomy, and only a few ductules were found around the large ducts. These results indicate that the existence of networks of bile ductules and the patency of large bile ducts at the porta hepatis contribute to good postoperative bile excretion. PMID- 2313499 TI - Intussusception-type antireflux valve in the Roux-en-Y loop to prevent ascending cholangitis after hepatic portojejunostomy. AB - An intussusception-type antireflux valve was created in the Roux-en-Y loop in 23 infants with biliary atresia (17 new cases, and six others after episodes of ascending cholangitis) and 10 patients with congenital bile duct dilatation, in order to prevent ascending cholangitis after hepatic portojejunostomy. Mesenteric blood vessels were divided in a 4 cm length of the Roux-en-Y loop, and the distal 1.5 cm of this portion was further denuded of the seromuscular layer; an antireflux valve was thus established by invaginating the proximal portion into the denuded jejunum. No case, in which this technique was used, was associated with any surgical complications, and ascending cholangitis never developed in any of the 17 new cases with biliary atresia, during an average follow-up of 32 months. PMID- 2313500 TI - The newborn piglet: a model of neonatal gastrointestinal motility. AB - Small intestinal myoelectric activity has been studied extensively in adult humans and in many animal models. However, little is known about gut myoelectrical activity in newborns, a population susceptible to primary and secondary motility disorders. We report the development of a chronic neonatal piglet model for assessment of gastric and small intestinal myoelectric activity. Six piglets aged 12 to 27 days and weighing 2.3 to 4 kg underwent laparotomy and implantation of four to six bipolar serosal electrodes along the small intestine; and selectively on the gastric antrum. Myoelectric records were obtained daily after operation in awake animals using low (0.16 Hz) and high (30 Hz) frequency filters. Electrical control activity (ECA) was observed in the stomach (4 to 5 cycles per minute) and in the duodenum (14 to 15 cycles per minute) on postoperative day 1; along with random bursts of spiking activity. The migrating myoelectric complex (MMC) appeared on postoperative day 2 or 3. In piglets followed for a week or more, the MMC cycle duration and phase III duration (period of maximal spiking activity) were longer in the proximal small intestine than at the terminal ileum (80 +/- 5 versus 47 +/- 3 minutes and 5.1 +/- 0.3 versus 3.7 +/- 0.1 minutes, respectively; mean +/- SEM, P less than .005), suggesting that some MMCs arise spontaneously in the distal small bowel without traversing the upper intestine. The antral and duodenal ECA frequencies are similar to values reported in human adults; the MMC cycle duration is slightly shorter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313501 TI - Necrotizing enterocolitis in multiple-birth infants. AB - Over a 5-year period, 20 infants of multiple-gestation births (16 twin, 2 triplet) developed necrotizing enterocolitis (NEC) (15 infants) or suspected NEC (5 infants). During the same period, 532 infants of multiple gestations were admitted to our neonatal intensive care unit, yielding a NEC incidence in this population of 3.8%. In two twin sets, both infants developed NEC or suspected NEC, and in three sets only the affected twin was transferred to our nursery. Five infants required surgical intervention (25%) and three infants died (overall mortality, 15%). Fifteen siblings who did not develop NEC served as a control group. Analysis showed that the 1-minute Apgar score was the most significant factor in predicting NEC (P less than .028) and need for surgical intervention (P less than .020). In this series, 82% of the infants with 1-minute Apgar less than 6 developed NEC, whereas 31% with 1-minute Apgar greater than 6 developed NEC. PMID- 2313502 TI - Familial Hirschsprung's disease--a report of 22 affected siblings in four families. AB - Twenty-two infants, belonging to four families from Gaza, presenting with typical features of Hirschsprung's disease are reported. Eight patients died at home shortly after birth, prior to 1974, due to low intestinal obstruction. Fourteen patients were referred to Hadassah University Hospital after 1974 and diagnosed, by rectal biopsy, as having Hirschsprung's disease. Thirteen underwent laparotomy and multiple intestinal biopsies. Ten had total intestinal aganglionosis, two had total or near total aganglionosis, and in only one patient was the common rectosigmoid aganglionosis found. One patient died prior to surgery. This unusual familial disease, involving very long aganglionic segments, raises the possibility that these infants suffered from a unique variant of Hirschsprung's disease. PMID- 2313503 TI - Fifteen years' experience of neuroblastoma: a prognostic evaluation according to the Evans and UICC staging systems. AB - Our policy of preoperative and postoperative adjuvant therapy of advanced neuroblastoma changed from mild to aggressive chemotherapy in 1978. In order to evaluate the clinical effects of this policy, 39 cases before 1977 and 37 cases after 1978 were retrospectively reviewed using the Evans and the International Union Against Cancer (UICC) staging systems. Both clinical stages (CS) and postsurgical histopathological stages (PS) of the UICC staging system showed an almost 100% cure rate in stages I (CSI, PSI) and II (CSII, PSII). The cure rates of CS III, PS IIIA, and PS IIIB cases were remarkably improved after 1978, but those of CS IV and PS IV cases remained extremely low. However, it was found that a disease-free survival rate of advanced neuroblastoma could be produced by complete resection of the tumor accompanied by adjuvant chemotherapy. In these conditions, we found that for predicting the prognosis of advanced neuroblastoma, the UICC staging system, especially the PS staging system, may be more rational than the Evans staging system. PMID- 2313504 TI - Inguinal pathology and its association with classical bladder exstrophy. AB - One hundred thirty-four cases of classical bladder exstrophy, managed at our institution, were reviewed. Fifty-six percent of the boys and 15% of the girls developed inguinal hernias over an average follow-up time-span of 10 years. Thirty-one percent of the patients with hernias underwent repair at the time of initial bladder closure. Forty-six percent of the patients who developed a hernia were diagnosed during the first year following their initial procedure. More than 50% of the individuals in the latter category presented with an incarcerated hernia, and required emergent management. Boys managed by staged reconstruction had a statistically significant risk of developing an inguinal hernia (P less than .001) compared with boys undergoing primary cystectomy and diversion. We believe the increased incidence of herniation with this congenital anomaly is secondary to a lack of obliquity of the inguinal canal, due to pubic diastasis along with an increased elevation of intraabdominal pressure following initial closure of the abdominal wall and bladder plate. To decrease the attendant morbidity of incarcerated hernias in this population, we stress the need for careful physical examination of the inguinal region and spermatic cord prior to surgery, along with repair of the patent processus vaginalis at the time of initial repair. PMID- 2313505 TI - Ectopia of the vas deferens. AB - Ectopic location of the vas deferens is a rare congenital abnormality that has a spectrum of presentations. Such cases have been associated with anorectal anomalies. Knowledge of distal Wolffian duct embryology may help to explain the developmental steps involved in these anomalies, as well as provide theories for the variations that may be encountered. Vas deferens development is reviewed, and two cases of vas ectopia are presented to illustrate and lend support to current theories of normal and abnormal vasal embryology. PMID- 2313506 TI - The role of routine radiographic screening of boys with hypospadias: a prospective study. AB - One hundred fifty-three asymptomatic boys with hypospadias were screened routinely by intravenous pyelography and voiding cystourethrography. Urinary tract abnormalities were found in 23.53%. Significant abnormalities were found in 11% on initial examination, and on follow-up, a further 4.5% required later surgery. The overall incidence of surgical interference, not including hypospadias repair, was 11.76%. Thus, routine urinary tract radiological screening in boys with hypospadias is recommended. PMID- 2313507 TI - Cyclic neutropenia with colonic perforation and nonhealing colocutaneous fistula. AB - Cyclic neutropenia is an hereditary disorder of white blood cells, characterized by profound neutropenic episodes approximately every three weeks. Septic complications are usually limited to cutaneous and oropharyngeal infections. A 4 year-old boy with known cyclic neutropenia was in shock with neutropenia, clostridial septicemia, and right lower quadrant peritonitis when he was admitted. At the time of laparotomy, inflammation of the cecum, with no gross perforation, was found; no resection or appendectomy was done. He subsequently developed a right lower quadrant abscess that was drained, resulting in a colocutaneous fistula. For the next 8 months his fistula persisted, with intermittent episodes of fever, increased fistula output, and abdominal pain during his neutropenic periods. Standard nonoperative approaches to healing the fistula failed (ie, elemental feeds, total parenteral nutrition, irrigations, antibiotics, and drains). Attempts to medically abolish his neutropenic episodes using lithium, gammaglobulin, and steroids also failed. Ultimately, he underwent an ileocecal resection with primary anastamosis; the operation was done immediately following a neutropenic episode, in order to allow adequate healing of his anastamosis before his next period of neutropenia. Postoperative course was satisfactory, and he remains well after 8 months follow-up. This case, and several similar previously reported cases, illustrate that cyclic neutropenia may present with serious surgical complications. They also underlines the important role that neutrophils play in the healing of enteric fistulae. PMID- 2313508 TI - Solitary nonparasitic hepatic cyst causing abdominal distension and respiratory distress in a newborn. AB - This is a report of a girl infant born with a protuberant abdomen and respiratory distress. A cystic mass was excised from the liver. PMID- 2313509 TI - Bile plug syndrome: successful management with a mucolytic agent. AB - Common bile duct obstruction, in an infant with bile plug syndrome, was relieved at surgery with a mucolytic agent, after an unsuccessful attempt at clearing the biliary tree with saline irrigation. This procedure obviated choledochotomy in this patient, and may be of use in other infants with ductal obstruction complicating the inspissated bile, associated with gut rest, parenteral nutrition, or diuretic therapy. PMID- 2313510 TI - Gastric heterotopy of the biliary tract. AB - The case of a 12-year-old girl having cholestatic syndrome, due to the presence of gastric tissue in the gallbladder and extrahepatic biliary tract, is reported here. PMID- 2313511 TI - 1988 NAPNAP membership survey. Part II: characteristics of the members. AB - In 1988, the 2560 members of NAPNAP were surveyed about their educational preparation, demographic characteristics, and professional employment status. Questions were included on members' opinions about issues that should be emphasized by NAPNAP in the future. Approximately 52% of the members returned usable questionnaires. In this second part of the survey results, we report the characteristics of members, how these characteristics have changed over time, and what the members believe NAPNAP's future priorities should be. PMID- 2313512 TI - Sibling relationships: more important now than ever. PMID- 2313513 TI - Physiologic sequelae of prematurity: the nurse practitioner's role. Part II. Retinopathy of prematurity. AB - Retinopathy of prematurity is a common complication in the treatment of premature birth. This article, the second in a series on the physiologic sequelae of prematurity, presents the pathophysiology of this condition, as well as the effects on the child's growth and development. Common problems faced by these children and their families are discussed, and parental counseling needs are presented. PMID- 2313514 TI - AIDS knowledge and attitudes of primary grade teachers and students. AB - This study was conducted to assess knowledge of and attitudes toward AIDS in primary grade teachers and students before the implementation of a mandated AIDS curriculum. Teachers and children completed questionnaires. Although both the teachers and the children were knowledgeable about some aspects of AIDS, both groups revealed misconceptions and misinformation. A high percentage of the children reported a fear of getting AIDS even though they constitute a very low risk group. Deficiencies in knowledge and fear of AIDS underscore the importance of the provision of accurate information to both teachers and elementary school children. Implications for school nurses and other health care providers are discussed. PMID- 2313515 TI - The treatment of avulsed teeth. AB - More than 2 million teeth are accidentally avulsed each year in the United States. Most of the victims are children. Almost all of these teeth can be saved if the proper treatment is instituted. Regardless of the frequency with which it occurs, every pediatric health care provider must be prepared for patients who have avulsed teeth. By instituting the proper treatment, the provider may help to save a victim's tooth, thus saving the family and child the expense of dental treatment and the possible psychologic problems associated with false teeth. Each health care provider should take the following steps: 1. Inform all health care personnel that avulsed teeth can and should be saved. 2. Teach all health care personnel what action should be taken if a tooth is avulsed. 3. Fabricate or purchase tooth-preserving devices such as the Emergency Tooth Preserving System, which can safely store, preserve, and transport avulsed teeth. 4. Place these tooth-preserving devices at strategic locations such as in emergency kits or at nurses' stations. PMID- 2313516 TI - Sexual abuse of children. PMID- 2313517 TI - Sex education for children and adolescents. PMID- 2313518 TI - Periodontal conditions following treatment with distally extending cantilever bridges or removable partial dentures in elderly patients. A 5-year study. AB - The aim of the present study was to evaluate the periodontal conditions following treatment with distally extending cantilever bridges or removable partial dentures (RPDs) in elderly patients. All participants had a complete denture in the maxilla and moderate-to-advanced bone loss around the teeth present in the mandible. After undergoing periodontal treatment, 27 patients were treated with distally extending cantilever bridges and 25 patients with a RPD. During the first 2 years following prosthetic treatment, the patients were recalled twice a year and during the last 3 years once a year for oral prophylaxis and assessment of the periodontal status. The patients treated with a RPD showed higher mean Plaque and Gingival Indexes than the patients treated with cantilever bridges. No change in probing pocket depths was observed in either group, and only a small decrease in radiographic alveolar bone height was revealed. In conclusion, only minor changes in the periodontal conditions were recorded during the 5 years of observation after treatment with cantilever bridges or RPDs. PMID- 2313519 TI - In vitro release of doxycycline from bioabsorbable materials and acrylic strips. AB - Treatment of marginal periodontitis may include use of local antibiotics. In the present in vitro study the bioabsorbable materials Surgicel, Tissell, and CollaCote and acrylic strips were examined for release of doxycycline into liquids and residual antibacterial activity of the materials. Pieces of material were incubated in 1 ml of water or human serum which was exchanged every day for 9 days. The concentration of doxycycline in the liquids was measured spectrophotometrically while the residual antibacterial activity of the materials was determined microbiologically. Surgicel constantly showed very high concentrations and level of residual activity. The acrylic strip and CollaCote decreased to low levels of both concentration and residual activity in a few days. Tissell was intermediate with a continuous decrease in concentration but rather high level of residual activity throughout the study. In serum the acrylic strip was partly dissolved and Surgicel was totally dissolved after 2 days. Left undisturbed in serum Surgicel was not dissolved for 2 weeks. These results indicate that Surgicel and Tissel may be capable of prolonged release of doxycycline in vivo. PMID- 2313520 TI - Bacterial penetration of gingiva in the adult beagle dog with periodontitis. AB - Invasion of gingival tissues by bacteria is thought to be a major factor in development of periodontal lesions. Morphologic studies have revealed bacteria within the pocket epithelium, gingival connective tissues, alveolar bone, and oral epithelium. The current studies are intended to determine whether they are present in healthy and diseased tissues and to identify the microbial source. Five beagle dogs with naturally occurring periodontitis were fed a soft diet. Two quadrants of the dentition of each dog were cleaned regularly and health maintained while others were allowed to develop further disease. After 4 weeks, samples of gingiva were removed both prior to and after the animals were sacrificed by perfusion fixation attempting not to introduce microorganisms. The identical samples were examined by light and scanning electron microscopy for numbers and location of organisms. Their numbers were greater in diseased than in healthy tissues. Furthermore, the quantity was greater in samples taken prior to perfusion fixation than after such treatment, especially in the oral epithelium. The results suggest that normally there are some microorganisms present within the periodontal tissues and that their numbers are greater in diseased tissues. However, the data also indicated that significant numbers may be introduced into the tissues during sampling of unfixed tissues. PMID- 2313521 TI - A mineral-related feature of young plaque characteristic to periodontitis affected adults. AB - The calcium concentration of 3-day-old total supragingival plaque in periodontitis-affected adults (n = 12) and their age and sex-matched periodontitis-free pairs was compared. The young plaque of the periodontitis affected adults contained more calcium per protein (P less than 0.025, sign test) than that of the periodontitis-free pairs. The findings of the present study may suggest that high Ca-content of supragingival plaque is connected to the development of adult periodontitis. PMID- 2313522 TI - Furcation defects in dogs treated by guided tissue regeneration (GTR). AB - This study evaluated the effects of guided tissue regeneration (GTR) in the treatment of Class II furcation defects in beagle dogs. Gore-Tex periodontal material was used, and the amount of furcation fill and the surface area corresponding to new connective tissue attachment and new bone were evaluated. If present, epithelium was also evaluated. Six female dogs with naturally-occurring periodontitis were given thorough root debridement. Four weeks later mucoperiosteal flaps were raised, involving the mandibular 2nd, 3rd, and 4th premolar and 1st molar teeth. After debridement, notches were placed on the roots at the level of furcal alveolar bone. Gore-Tex material was adapted to the furcation and secured with sutures on two teeth of each quadrant. The flaps were sutured tightly, making sure the margin of the material was covered. Teeth receiving only surgery acted as controls. Gore-Tex material was removed 1 month following surgery. All dogs were sacrificed by exsanguination at 3 months. Mesiodistal sections were evaluated by descriptive histology. Surface area determination of the furcal tissues was carried out using a microscope attached to a computerized digitizer. Approximately 10 serial sections per tooth were evaluated. Mean values for each dog were obtained for experimental and control teeth and analyzed using paired t-tests (N = 6) to see whether different treatments had any effect on the parameters tested. Different degrees of fill were seen with epithelium, new connective tissue, and bone. Statistically, GTR gave significantly better results in the amount of connective tissue and bone fill achieved. PMID- 2313523 TI - Effect of benign familial neutropenia on the periodontium of Yemenite Jews. AB - The purpose of this study was to compare the periodontal status of Yemenite Jews with and without benign familial neutropenia (BFN). Thirty-four volunteers were examined at baseline and after 3 years. Plaque index (PlI), bleeding index (BI) probing depth (PD), and attachment levels (AL) were recorded. Differential blood counts were done on at least three occasions during the study. Volunteers with at least one count of less than 2000 neutrophils were considered neutropenic. The majority of patients received oral hygiene instructions and scaling at the initial visit. During the study there was a significant drop in PlI (P less than 0.01) and BI (P less than 0.05). At baseline the BFN and non-BFN volunteers had similar PlI, but the BI was significantly greater in the BFN group. At follow-up, there was a significantly greater number of teeth with pockets greater than or equal to 6 mm in the BFN group (P less than 0.05). These results indicate that volunteers with BFN, a phenomenon that has not previously been associated with any pathology, are more susceptible to gingival inflammation and attachment loss than unaffected volunteers and that they respond more favorably to an improvement in oral hygiene. PMID- 2313524 TI - Ectopic gingival sebaceous glands presenting as localized periodontitis. AB - The development of ectopic gingival sebaceous glands is a very unusual condition which is histologically similar to Fordyce's granules when they occur within the buccal or labial mucosa. In this report, we present a rare case of ordinarily innocuous, ectopic gingival sebaceous glands, which presented clinically and radiographically as localized advanced periodontitis. Histological and immunocytochemical evaluation of tissue removed from the periodontal lesion following excisional biopsy supported the diagnosis of an ectopic gingival sebaceous defect. This case illustrates the necessity of considering less frequently occurring entities in the differential diagnosis of localized lesions which appear to be periodontal in origin. PMID- 2313525 TI - An estimate of periodontal treatment needs in the U.S. Based on epidemiologic data. PMID- 2313526 TI - Characterization of fibroblasts derived from human periodontal ligament and gingiva. AB - Growth characteristics and macromolecular synthesis of fibroblasts derived from human periodontal ligament (PDLF) and gingiva (GF) have been compared in cell culture. Cells were isolated from explants and plated at 500,000 cells/100 mm culture dish (day 0) with daily changes of culture medium. DNA histograms were obtained by flow microfluorimetric analysis to confirm the growth state of the cell cultures. Human PDLF cultures became confluent at day 6 as determined by cell number and cell cycle analysis while GF were confluent by day 4. Initially, DNA content of logarithmically growing cells was significantly greater in GF cultures; however, when confluent, DNA content and cell number was greater in PDLF cultures. Total protein content in GF was slightly greater than PDLF until day 7 but this difference was not significant. Analysis of collagen and noncollagen protein synthesis revealed a greater trend in noncollagen protein synthesis in the GF cultures compared to PDLF cultures. Analysis of glycosaminoglycans in the culture medium of GF and PDLF revealed similar distributions of components. In the cellular fraction, GF had greater amounts of hyaluronic acid and heparin and lesser amounts of chondroitin sulfates A and C than PDLF cultures. The results indicate that the growth characteristics of PDLF and GF, although similar in many respects, do exhibit specific differences in proliferative rates and macromolecular synthesis. The differences observed in these parameters may be important during in vivo events, such as guided tissue regeneration, where significant functional differences are observed between gingival connective tissue and periodontal ligament connective tissue. PMID- 2313527 TI - Supragingival irrigation with 0.06% chlorhexidine in naturally occurring gingivitis. I. 6 month clinical observations. AB - The purpose of this study was to assess the efficacy of supragingival irrigation with 0.06% chlorhexidine gluconate (CHX) on naturally occurring gingivitis. The relative benefit of CHX irrigation in comparison with CHX rinsing, water irrigation, and normal oral hygiene was evaluated. In a blind, placebo-controlled 6-month study 222 patients were assigned to one of four groups: Group 1: Once daily irrigation with 300 ml water followed by irrigation with 200 ml 0.06% chlorhexidine gluconate (experimental); Group 2: Twice daily rinsing with 15 ml 0.12% chlorhexidine (positive control); Group 3: Once daily irrigation with 500 ml water (irrigation control) and Group 4: Sodium fluoride dentifrice for normal oral hygiene only (negative control). All groups used the same sodium fluoride dentifrice for tooth brushing. At baseline, 3 months, and 6 months patients were examined for Gingival Index (GI), Bleeding on Probing (BOP), Plaque Index (PLI), Pocket probing depth (PD), Calculus Index (CI), and stain. After the baseline visit all patients received a supra- and subgingival oral prophylaxis. At 6 months GI and BOP were significantly (P less than or equal to 0.05) reduced by adjunctive CHX irrigation (42.5% and 35.4%, respectively), CHX rinse (24.1% and 15.0%), and water irrigation (23.1% and 24.0%) compared to tooth brushing alone. Plaque was significantly (P less than or equal to 0.05) reduced only by CHX irrigation (53.2%) and CHX rinse (43.3%) while calculus and staining were significantly (P less than or equal to 0.05) increased in the two chlorhexidine groups (276.4% (irrigation) and 273.2% (rinse)). Although significant (P less than or equal to 0.05), pocket probing depth reduction was minimal after CHX irrigation (4.6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313528 TI - The apical location of calculus within the intrabony defect. AB - Although several studies have concluded that calculus removal becomes more difficult as pocket depth increases, few have examined the clinical location of calculus within the intrabony defect. This study evaluated the relationship between apical calculus position and the depth and morphology of the intrabony defect. As part of an on-going study of new attachment procedures in humans, 260 intrabony defects were surgically entered in 39 patients. Using magnifying loops and fiber optics in all defects, the most apical level of calculus was grooved to serve as both a clinical and histologic reference point. Clinical measurements made prior to root debridement included the alveolar crest to base of calculus, and the base of calculus to base of defect. The type of defect was classified by the number of remaining osseous walls. Calculus has not been found apical to the groove in any histologic section. The mean distance measured clinically between the base of the calculus and the base of the defect was found to increase with the depth of the defect. This relationship did not vary with either tooth type or number of remaining osseous walls in the defect. Data analysis of this group of patients (N = 39) showed a positive correlation (r = .83) between increasing depth of intrabony defect and the distance of the most apical calculus from the defect base. PMID- 2313529 TI - Patient preference for waxed or unwaxed dental floss. AB - The purpose of this study was to discover patient preference for waxed or unwaxed dental floss, and to learn more about individual flossing habits. One hundred patients randomly presenting for routine dental examinations volunteered to sample a brand of similar-appearing waxed and unwaxed dental floss. After flossing an anterior and a posterior contact area with both types, the patients indicated whether they preferred the waxed or unwaxed floss. The patients also answered questions concerning their flossing habits. Waxed floss was found to be preferred after sampling by 79% and unwaxed by 21%. An additional 50 patients sampled a different brand of waxed and unwaxed floss in a similar manner. In this group 78% preferred the waxed and 22% the unwaxed type. A final group of 50 patients compared mint flavored waxed floss with plain waxed floss of the same brand. In this group 56% preferred the mint flavored waxed floss, 24% the plain waxed floss, and 20% had no preference. A combined total of only 29.5% of the patients claimed to floss daily, 53.5% floss irregularly but at least once a week, while 17% do not floss even once a week. Waxed floss was purchased for home use by a combined patient total of 57.5%, unwaxed by 32%, and neither type by 10.5%. An unsubstantiated belief in the superiority of unwaxed floss has persisted to the present time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313530 TI - Multiple myeloma of the periodontium. A case report. AB - Multiple periodontal lesions were the presenting features leading to a diagnosis of multiple myeloma in a 38-year-old male. Ulceration and bleeding from a rapidly growing retromolar myelomatous mass, multiple foci of alveolar bone destruction and cortical expansion together with multifocal skeletal destruction were the hallmarks of the neoplastic process. Radiotherapy and chemotherapy brought a substantial, but temporary, remission with improvement of the periodontal condition. A sudden exacerbation of the died 22 months after the diagnosis was made. PMID- 2313531 TI - Prolonged systemic administration of cyclosporin A affects gingival epithelium. AB - Gingival biopsies were obtained from 12 patients suffering from Behcet's disease who were treated with Cyclosporin A (CsA) for up to 20 months. Preparations were made for examination with both light and scanning electron microscopy (SEM). Along with known changes in the gingival epithelial structure observed following CsA treatment, we also found unusual clusters of needle-like crystallites embedded in the epithelium, mostly at the base of the acanthotic projections. Toluidin blue staining revealed increased numbers of both intact and degranulated mast cells in the attached epithelium. It is concluded that CsA affects the gingival epithelium and that the clinically observed enlargement of gingival tissue following prolonged treatment with CsA is due primarily to CsA-epithelial interaction. PMID- 2313532 TI - Presidential address. PMID- 2313533 TI - Object representations in descriptions of significant others: a methodological study. AB - The aim of this methodological study was to extend Blatt, Wein, Chevron, and Quinlan's (1979) coding system for assessing levels of mental representations of others. Blatt devised a system for scoring spontaneous descriptions of parental figures on a scale that spanned five levels of object differentiation. A single level score was assigned. In this study a procedure was developed to generate scores for each of five representational levels, for two object descriptions, for each subject. The new procedure was based on the assumption that in each individual, all levels of differentiation are maintained albeit in varying proportions. The new coding method was tested in a contrast study in which the responses of a cohort of borderline patients were compared with those of a cohort of nonpsychiatric subjects. As predicted, all subjects were assigned scores at all five representational levels; however, the borderlines had a higher proportion of content units in the lower, least differentiated levels of object representation, and the nonpsychiatric subjects had higher scores at the more differentiated, conceptually complex levels. Results of the psychometric properties of the coding method are discussed. Work in progress to refine the method is outlined. PMID- 2313534 TI - The assessment of subjective well-being and its relationship to the stress process. AB - Research into relationships between stressors and adaptational outcomes has often represented well-being as the relative lack of pathological signs. However, such assessments do not discriminate between not being ill and experiencing degrees of subjective well-being (i.e., from feeling "OK" to feeling "Great!"). This article suggests that subjective well-being be more narrowly defined to refer strictly to positive indicators of health status. In this study, psychometric properties of a new instrument, the Well-Being Scale-36, were examined. Relationships between subjective well-being and components of the stress process were explored. The results indicated that well-being and various forms of pathology should be conceptualized as distinct but related entities. PMID- 2313535 TI - The measurement of criminal dangerousness as a personality construct: further validation of a research index. AB - The validity of an index measuring criminal dangerousness was further evaluated by determining whether it could discriminate among prisoners committing violent crimes at three levels of severity. The index score was a multiplicative product of an antisocially score and an IQ score, with high antisocially and low IQ reflecting greater dangerousness. Comparison of index scores for men committing murder (most severe); robbery and rape (intermediate severity); and assault, child molestation, and manslaughter (least severe) revealed a significant monotonic increase in dangerousness scores as increasingly severe crimes were considered. Several recommendations for the measurement of criminal dangerousness were offered. PMID- 2313536 TI - Rorschach structure of a hospitalized sample of Vietnam veterans with PTSD. AB - Rorschach structural summary data are presented for a group of 41 posttraumatic stress disorder (PTSD) patients who were being treated in a specialized inpatient PTSD treatment program. Results suggest that patients suffering from PTSD exhibit impaired reality-testing abilities and tend to utilize ineffective coping strategies. The group's structural summary factors are presented as incipient normative data for the Exner Comprehensive System on patients with PTSD. Implications that these protocols suggest a more severe and pervasive level of psychopathology than would be expected from theoretical descriptions of the disorder are discussed. PMID- 2313537 TI - An examination of the stability of the MMPI Personality Disorder Scales. AB - Recently, a set of Minnesota Multiphasic Personality Inventory (MMPI) scales for the diagnosis of personality disorders have attracted research attention. As personality disorders are thought to represent long-standing trait disturbances, any measure of these disorders should be stable over time and relatively free from state influences. This study investigated the stability of the MMPI scales in 67 subjects across a brief inpatient treatment for substance abuse. The results indicated high levels of stability across the 3-week treatment period. PMID- 2313538 TI - Comprehensive system Rorschach data on Vietnam combat veterans. AB - To better understand and, therefore, treat Vietnam combat veterans with a diagnosis of posttraumatic stress disorder (PTSD), the Rorschach was administered to 50 patients so diagnosed. The most important findings were that, on average: (a) These patients have a low level of stress tolerance and are, therefore, likely to respond impulsively to stressful situations; (b) this low stress tolerance appears to be a long-term adjustment problem; and (c) their perception of reality is unconventional and often distorted. A primary therapeutic indication from these data is that the use of structure would be important for successful therapy. Other findings and therapeutic recommendations are also discussed. PMID- 2313539 TI - Assessment of long-term psychosocial sequelae among POW survivors of the Korean Conflict. AB - Psychological and psychiatric assessments were performed among 20 prisoner-of-war (POW) Korean-Conflict survivors. Results revealed extraordinary biological and psychological abuse with weight losses exceeding 35% of preservice weights and long-term cognitive, emotional, and behavioral sequelae. The full range of posttraumatic stress disorder symptoms was seen in 90% to 100% of the cases with high prevalence of co-morbidity, specifically mood (75%), other anxiety (45%), and alcohol abuse (20%) disorders. Documented by clinical investigators at POW release and now more than 30 years later, symptoms of apprehensiveness, confusion, detachment, and depression reflect the persistence of psychiatric morbidity over time. PMID- 2313541 TI - A new measure of weight locus of control: the Dieting Beliefs Scale. AB - This article describes the construction and preliminary validation of a new scale of weight locus of control, the Dieting Beliefs Scale. The 156-item scale demonstrated moderate internal consistency and high test-retest reliability in a sample of undergraduate women. Principal-components analysis suggested three factors. The three factors were interpretable and had distinct relations with a variety of weight-related and psychological variables. The results suggest that weight locus of control is a multidimensional construct, and they provide a possible explanation for the inconsistent findings concerning the relation between weight locus of control and dieting success. Implications for the study of dieting relapse and for the construction of treatment programs are discussed. PMID- 2313540 TI - A comparison of two multidimensional health locus of control instruments. AB - This study examined the factor structure, internal consistency reliability, and construct validity of the multidimensional health locus of control (MHLC) instruments developed by K.A. Wallston, B.S. Wallston, and DeVellis (1978) and Lau (Lau, 1982; Lau & Ware, 1981). Both measures were administered to a sample of Veterans Administration (VA) medical outpatients (N = 181). Only minimal evidence of convergence was found between corresponding scales of the two MHLC instruments. Low convergent validity appears attributable to the poor internal consistency reliability of the Lau-Ware subscales. Moreover, results of factor analysis largely supported the a priori factor structure of the K.A. Wallston et al. (1978) MHLC instrument but failed to support the factor structure of the Lau Ware instrument. Health locus of control (HLC) dimensions that emerged from simultaneous factor analysis of both instruments were most consistent with a three-dimensional typology (i.e., Personal Control, Professional Control, and Chance) rather than the four-dimensional typology proposed by Lau (Lau, 1982; Lau & Ware, 1981). Implications for HLC conceptualization and measurement are discussed. PMID- 2313542 TI - The Body Esteem Scale: construct validity of the female subscales. AB - The female subscales of the Body Esteem Scale (BES) have demonstrated convergent and discriminant validity in two previous studies. However, relationships between BES dimensions, weight, and other body-image measures have not been adequately examined. In this study, 200 women with a mean age of 27.6 years completed the BES, the Eating Disorder Inventory, the Self-Consciousness Scale, the Tennessee Self-Concept Scale, a figure rating task, a phototechnical body-size estimation procedure, and items concerning weight satisfaction and attractiveness. BES Weight Concern was most closely related to weight variables and other body image measures where BES Sexual Attractiveness and Physical Condition were more strongly associated with less specific self-perceptions and attitudes. Results support the construct validity of the BES female subscales and their utility for research in populations at increased risk for body-image or eating-disorder disturbances. PMID- 2313543 TI - Body image or body images?: Comparative, multidimensional assessment among college students. AB - A major criticism of research on body image concerns the dubious assumptions of the unidimensionality of the construct and the equivalence of body-image measures. Our study of 125 male and female college students compared multiple measurement methods within each of two modalities of body image: (a) perceptual (body-size estimation) and (b) attitudinal (body-image affect and cognition). Clinically relevant indices of psychological adjustment and eating disturbance were included. Results clearly supported the distinction between attitudinal and perceptual modalities of body image and indicated more convergent and discriminant validity for the former than for the latter. Whereas one method of assessing size-estimation accuracy and most body-image attitudes produced relationships with maladjustment, only attitudinal body image and perceptual, self-ideal discrepancy measures were significantly linked to eating disturbance. Relationships were generally more consistent for women than for men. Implications are discussed in the context of extant and future research on body image with clinical and nonclinical populations. PMID- 2313544 TI - Type T personality and the Jungian classification system. AB - The Type T personality has been described as a personality dimension referring to individual differences in stimulation seeking, excitement seeking, thrill seeking, arousal seeking, and risk taking. This article explores its relationship to the theoretically relevant personality classification system of C.G. Jung, employing the Myers-Briggs Type Indicator as a measure of Jungian types. A sample of high-school students was administered the Myers-Briggs and a measure of Type T. Pearson correlations revealed Type T to be significantly related to the Jungian Intuitive and Perceptive types, with the Type T personality being described as intuitive and perceptive. Interpretations of these exploratory findings were offered. PMID- 2313545 TI - Use of the TAT to measure change in defense mechanisms following intensive psychotherapy. AB - Changes in the use of defense mechanisms (denial, projection, and identification) were examined over a period of approximately 15 months of intensive treatment of 90 seriously disturbed young adults who were hospitalized in an intensive, open, long-term treatment setting. Patients independently judged to have primarily an anaclitic or an introjective personality configuration (Blatt, 1974; Blatt & Shichman, 1983) were assessed for psychiatric symptoms and aspects of interpersonal behavior both on admission and after an average of 15 months of treatment. Findings based on an independent assessment of TAT protocols at these two times indicated a significant (p less than .05) decline in total use of defenses for the entire sample, but especially for introjective patients. Further, this decline in total use of defenses in the TAT was significantly associated with a reduction in psychiatric symptoms. Also, sex-incongruent patients (anaclitic men and introjective women) were found to use different defenses and to change in ways different from sex-congruent patients (anaclitic women and introjective men). PMID- 2313546 TI - The discrimination of patient-generated and randomly generated MMPIs. AB - A discriminant analysis was applied to 34 randomly generated and 34 patient generated Minnesota Multiphasic Personality Inventory (MMPI) profiles. The discriminant was able to differentiate the two sets at greater than 97% accuracy. A cross validation based on derived unstandardized canonical discriminant functions was carried out on an additional 10 random and 10 patient MMPIs. It attained 95% accuracy. Eight experienced clinical psychologists attained less than 70% accuracy--six of the eight did no better than chance. The importance of including actuarial data in validity judgments was discussed. PMID- 2313547 TI - The Survey of Achievement Responsibility (SOAR): reliability and validity data on an academic attribution scale. AB - The Survey of Achievement Responsibility (SOAR) was designed to assess students' causal attributions of success and failure in school-related situations. Unlike other measures of locus of control and attributions, the SOAR simultaneously distinguishes among three broad subject areas--math/science, language arts/social studies, and physical education--and between two possible outcomes--success and failure. Data on the psychometric characteristics of the SOAR came from two samples from each of two large school districts, one suburban and one metropolitan. A five-stage study of the psychometric qualities of this new instrument revealed: (a) Content validity is high--judges independently classified items into the attribution categories intended by the authors; (b) internal consistency reliabilities are in a range adequate for group research purposes and are comparable to the reliabilities of other measures of attributions; (c) test-retest reliabilities showed attribution profiles to be stable over a 2-month interval; (d) correlations between the SOAR scales and students' self-reports of ability in various subject areas showed differential relationships in theoretically predicted directions; and (e) correlations between the SOAR scales and achievement tests were statistically significant, though low in magnitude, consistent with reports on other instruments. Finally, use of the SOAR in a spectrum of studies has demonstrated its research utility and indicated directions for further instrument development and research. PMID- 2313548 TI - The relationship between defenses and symptoms in adolescent psychopathology. AB - The relationship between defense mechanisms and symptoms was assessed in a group of 196 psychiatrically hospitalized adolescents. Defense mechanisms were measured through the use of the Defense Mechanisms Inventory (DMI); symptoms and problem behaviors were measured with the Youth Self-Report. Univariate and multivariate analyses indicated that externalizing symptoms are associated with defenses that locate the conflict outside of the self, whereas internalizing symptoms are associated with defenses that locate the conflict within the self. In contrast to previous reports, no gender differences were found in defense preference, though gender differences were found in the relation of defenses to symptoms. The findings are consistent with clinical theory of defense processes and support the distinction between internalizing/externalizing behaviors and personality dimensions for both symptoms and defenses. The study supports the validity of the adolescent form of the DMI. PMID- 2313549 TI - MMPI supplemental scale performance of Mexican Americans and level of acculturation. AB - Mexican American and Anglo American's performance on the Wiggins Content Scales, Harris-Lingoes subscales, and Serkownek subscales was assessed in a college student population. Level of acculturation (Mexican vs. Anglo orientation), age, and social class were statistically controlled. The results showed statistically significant differences between means of Anglo and Mexican Americans on most of the supplemental scales assessed. These differences were more numerous before scale validity criteria were applied. The number of statistically significant differences were further reduced when level of acculturation and age were statistically controlled. The results showed that level of acculturation is a highly important variable which moderates interpretation of the MMPI scale elevations we measured. Acculturation far outweighed the influence of the well established MMPI moderator variables of age and social class. PMID- 2313550 TI - MMPI characteristics of professional prostitutes: a cross-cultural replication. AB - The personality characteristics of 41 professional prostitutes in Brussels, Belgium, were examined using either a French- or a Flemish-language version of the Minnesota Multiphasic Personality Inventory (MMPI). A comparison group of 96 nonprostitute women was recruited from among employees of an international airline. Age differences within the prostitute group were also examined. In some contrast to prior research findings, the prostitute group was significantly more deviant on several indicators of psychopathology. Also, older prostitutes were more deviant than younger ones. An appreciable number of the women in this profession are in need of psychological treatment. PMID- 2313551 TI - Discriminating personality disorders using the WAIS-R: a comparison of three approaches. AB - The purpose of this article is to determine if performance on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) can be used to discriminate between the different taxonomies of personality disorder classification specified by three models: the biosocial, the interpersonal, and that described by the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987). Three discriminant function analyses were performed and the results indicated the usefulness of the WAIS-R in making such differentiations for all the approaches. The WAIS-R proved most effective with the biosocial model, evidencing a robust and clinically meaningful pattern of results. Implications for further research are discussed. PMID- 2313552 TI - Recent adolescent MMPI norms: T-score elevation comparisons to Marks and Briggs. AB - Minnesota Multiphasic Personality Inventory (MMPI) norms developed by Marks and Briggs (1967/1972) have served as the standard adolescent norms used for over 10 years. Additional adolescent norms have recently been produced by Gottesman, Hanson, Kroeker, and Briggs (1987) and by Colligan and Offord (1989), thereby providing MMPI users with a potential choice of adolescent norms. Our study examines the effects of these adolescent norm sets on single-scale and profile elevations. In addition, we examine the ability of these norm sets to generate T score values that would serve to discriminate accurately among adolescents in outpatient (n = 100), inpatient (n = 100), and normal (n = 100) settings. Results indicated that the choice of adolescent norms resulted in important differences in profile elevation. Findings from the discriminant function analyses, however, indicated that these normative sets were roughly equivalent in discriminating among adolescents in the three settings. PMID- 2313553 TI - Assessing individual differences: effects of responding to prior questionnaires on the substantive and psychometric properties of self-esteem and depression assessments. AB - It has become a common practice among psychological researchers to administer batteries of individual difference assessments to research participants, although little is known about whether the substantive and psychometric integrity of the questionnaires are maintained when they are administered after the subject has completed other instruments. The studies presented here consider these issues in relation to the assessment of self-esteem and depression. In the first study, college students responded to a self-esteem inventory (a) by itself (control group), (b) after one prior questionnaire, (c) after three prior questionnaires, or (d) after five prior questionnaires. Results indicated that filling out one or more questionnaires before an assessment of self-esteem resulted in reports of lower self-esteem relative to the control condition. Additional analyses revealed that filling out three or five prior questionnaires created lower reliabilities of subscale scores and lower estimates of concurrent validity between self-esteem and depression. When the effect of prior questionnaires on the General Self Esteem subscale was examined, the aforementioned results were replicated, and the prior questionnaire treatment created heterogeneous variances across the experimental groups. The second study was designed as a replication of the first study, using an assessment of depression as the target questionnaire. These results revealed that reports of depressive symptomatology increased as the number of prior questionnaires increased. Again, the prior questionnaire treatment created heterogeneity of variance between the groups, but did not adversely affect its internal consistency. PMID- 2313554 TI - Rorschach Erlebnistypus and problem-solving styles in children. AB - This study was designed to determine whether introversive versus extratensive children differed, on the basis of their Rorschach Erlebnistypus score, with respect to their approaches to three subtests (Block Design, Object Assembly, and Mazes) of the Wechsler Intelligence Scale for Children-Revised. It was thought that the extratensives would manipulate the test materials more and make more mistakes than the introversives, owing to the notion that introversives would internalize more of their manipulations and attempted solutions. Analysis of the data revealed mixed results. PMID- 2313555 TI - Personality dimensions in two types of learning-disabled children: a Rorschach study. AB - Children referred for psychoeducational assessment of learning disabilities (LDs) commonly receive the Rorschach test. yet little is known about the impact of LD on Rorschach response patterns. This study investigated Rorschach response patterns in two groups of 9- to 12-year-old children (n = 41) classified by their respective intellectual abilities. Another group of 9- to 12-year-olds (n = 143) served as a nonclinical comparison group. Rorschach variables indicative of personality dimensions failed to discriminate between the two LD groups. Compared to the nonclinical group, the LD group exhibited several Rorschach characteristics--including problems in perceptual accuracy, inefficient visual scanning and problem-solving strategies, and avoidance of affect-laden stimuli- having implications for successful socioemotional adaptation. Suggestions for further research are discussed. PMID- 2313556 TI - Differentiation of personality types among opiate addicts. AB - A wide range of studies indicate that although sociopathic characteristics are predominant in opiate addiction, depressive and psychotic features are also frequently observed. To test the hypothesis that there are really three types of individuals who become addicted to opiates (rather than a single, predominant personality style), fifty-three opiate addicts were given the Loevinger Sentence Completion Test, the Bellak Ego Functions Interview, and the Rorschach. Variables derived from these three procedures were submitted to cluster and discriminant function analyses. Three groups of addicts were identified--those primarily with impaired interpersonal relationships and affective lability (42%), those primarily characterized by thought disorder and impaired ego functioning (30%), and a group with diminished ideational and verbal activity (28%). Comparison of the assessment of these three groups with independently defined normal, neurotic, and schizophrenic samples provided support for three opiate-addicted personality types, each respectively characterized as character disordered, borderline psychotic, and depressed. Although there seems to be a predominance of character disordered individuals who become addicted to opiates, the data indicate several additional types of opiate addicts with different types of psychopathology who may require different approaches to management and treatment. PMID- 2313557 TI - Policy implications of the AIDS deficit. PMID- 2313558 TI - Therapy may explain recent deficits in AIDS incidence. AB - Since the middle of 1987, fewer consistently defined AIDS cases have been reported than expected among homosexual and bisexual men in the United States. This "AIDS deficit" was greater among homosexual and bisexual men in New York City, San Francisco, and Los Angeles, but was also striking among all homosexual and bisexual men in the United States. Deficits were virtually absent among intravenous drug users (IVDUs) in the United States. Three independent sources of data--placebo-controlled trials, pharmaceutical company reports, and the San Francisco Men's Health Study--were used to demonstrate that the amounts of zidovudine (AZT) given prophylactically to those at highest risk of AIDS since March 1987 have been sufficient to account for most of the observed AIDS deficits. Other advances in the medical care of pre-AIDS patients may have combined with AZT to produce the deficits. Other hypothesized explanations were examined and found insufficient to account for the observed AIDS deficits, including: (a) a sudden halt in new human immunodeficiency virus (HIV) infections during the early or mid-1980s; (b) misspecification of the distribution of AIDS incubation times following HIV infection; (c) increasing delays in the reporting of AIDS cases; (d) changes in the surveillance definition of AIDS in 1987; and (e) evolution of attenuated HIV strains. The hypothesis that therapy is affecting national AIDS rates has important implications. Failure to take the effects of therapy into account can lead to serious underestimates by back-calculation of the cumulative numbers infected with HIV and of AIDS incidence over the longer term. Moreover, it appears that AIDS incidence could be retarded in underserved groups, such as IVDUs, by making AZT and other state-of-the-art treatments readily available to AIDS-free patients with advanced immunodeficiency. PMID- 2313559 TI - Sex, drugs, and HIV infection in a New York City hospital outpatient population. AB - Persons attending outpatient clinics at Bellevue Hospital Center in Manhattan, New York City were invited to be tested for antibodies to human immunodeficiency virus (HIV). In pretest counseling, males were asked if they had injected nonprescription drugs or engaged in sex with other men since January 1, 1977; if so, they were asked not to participate and were referred elsewhere for testing. Face-to-face interviews and HIV testing were completed for 1,119 subjects with no prior indication of HIV seropositivity. Willingness to participate in the study was significantly greater among women than men and among younger than older persons. After exclusion of two subjects with indeterminate HIV serology, seroprevalence was 6.3% (70/1,117) overall, 7.1% (26/368) among men, and 5.9% (44/749) among women. HIV seropositivity among female i.v. drug users was 37% (27/74). Among heterosexuals without other HIV risk factors, estimated seroprevalences were 2.7% (25/924) overall, 3.3% (10/305) among males, and 2.4% (15/619) among females. Among heterosexual men, the data suggested associations of HIV seropositivity with sex with prostitutes and sex with numerous partners. Multiple logistic regression analysis indicated that significant predictors of HIV infection among women were a history of sexual contact with a male intravenous drug user, recent last use of intravenous drugs, and long duration of residence in New York City. Sexual intercourse with persons from AIDS risk groups was reported by 11% of men and 18% of women. The modal method of birth control reported by both men and women was "no method". PMID- 2313560 TI - HIV-1, sexual practices, and contact with foreigners in homosexual men in Colombia, South America. AB - From October 1985 to November 1987, a sample of 294 Colombian homosexual men volunteered to answer a questionnaire on sexual practices and consented to HIV-1 testing. Testing for HIV-1 was performed using an ELISA and those positive were confirmed with envelope- and core-specific ELISAs. Statistical methods for data analysis included Mantel-Haenszel methods on contingency tables. The overall seropositivity rate was 21.1%. Subjects who reported a receptive role (either as predominantly receptive or as mixed receptive-insertive intercourse) had a seropositivity rate of 23.7%, which was significantly higher than the 10.3% found in those reporting predominantly insertive intercourse (RR = 2.30, 95% C.I. = 1.16-4.57). For subjects reporting receptive intercourse, sexual contact with foreign visitors was a significant risk factor for HIV-1 infection (RR = 1.84, 95% C.I. = 1.13-3.00). Factors of borderline significance included having had more than ten homosexual partners in the preceding year (RR = 1.53) and a history of international travel (RR = 1.43). These associations did not hold for those reporting predominantly insertive intercourse. The data indicate the need to monitor the spread of HIV-1 at the international level and provide information on subgroups of high transmission rates. PMID- 2313561 TI - Indwelling central venous catheter infections in patients with acquired immune deficiency syndrome. AB - Indwelling central venous catheters are increasingly useful in the clinical management of patients with acquired immune deficiency syndrome (AIDS). To evaluate the risk of catheter infection in this group of patients, we reviewed the records of 299 patients with Hickman and Port-a-cath catheters. Patients were stratified into three groups: (a) AIDS (n = 54), (b) non-AIDS immunodeficiencies (n = 102), and (c) immunocompetent (n = 98). The rate of infection per 1,000 catheter days was 2.02, 0.41 (p less than 0.002), and 0.23 (p less than 0.002), respectively. Gram-positive cocci were the predominant isolate. Previous catheter infection and advanced AIDS (as determined by positive p24 antigen and low CD4+ number) were associated with increased risk of infection. Exit, tunnel, and fungal infections required catheter removal. The risk of infection and management were similar in Hickman and Port-a-cath catheters. The mortality was extremely low in all groups. However, the risk of infection associated with indwelling catheters was significantly higher in AIDS patients compared to patients with other immunodeficiencies. PMID- 2313562 TI - Heat-labile, complement-like factor(s) of animal sera prevent(s) HIV-1 infectivity in vitro. AB - We studied inactivation of HIV-1 by fresh sera of animals. We found that while fresh sera of humans and chimpanzees (among others) did not have antiviral activity, fresh sera of several other mammals, especially those of rodents and felines, showed a dose-dependent viral-inactivating property against cell-free HIV-1; these sera were also capable of inactivating virus preadsorbed to cells, similar to neutralizing antibody. The activity was destroyed by heating to 56 degrees C, required Ca2+ but no antiviral antibody, and therefore apparently involves the classical complement pathway. The activity could not be ascribed to any single fraction of sera separated on a size exclusion HPLC column. Mouse serum (the only one tested) also inactivated HIV-2. The data are consistent with classical C-mediated pathway inactivation of HIV-1 and HIV-2 by animal sera and is the first report of any "complement-like" antilentiviral serum factor. Elucidation of this mechanism may aid in understanding the lack of activity of human serum against HIV-1 and may prove useful in combined interventive strategies against HIV-1. PMID- 2313563 TI - Epidemiology and prevention of AIDS among intravenous drug users. PMID- 2313564 TI - Obstacles to the optimal management of HIV infection/AIDS in Africa. PMID- 2313565 TI - Global AIDS into the 1990s. PMID- 2313566 TI - Issues involving women, children, and AIDS primarily in the developed world. PMID- 2313567 TI - Humanity, the measure of an ethics for AIDS. PMID- 2313568 TI - Number of patients treated with zidovudine in the limited distribution system, March-September, 1987. PMID- 2313569 TI - Interaction of caffeine with L-tryptophan: study by 1H nuclear magnetic resonance spectroscopy. AB - The interaction of caffeine with L-tryptophan was investigated in aqueous solution adjusted to an ionic strength of 0.20, at pH 6.2, by using 1H NMR spectroscopy. Caffeine interacted with L-tryptophan at a molar ratio of 1:1 by parallel stacking. The thermodynamic parameters obtained for the complexation were as follows: delta G degree = -1.70 kcal/mol at 25 degrees C (K = 17.6 M-1), delta H degree = -3.7 kcal/mol, delta S degree = -6.7 eu. It was found that the driving force for parallel stacking is a combination of electrostatic, polarization, and dispersion interactions, and the contribution of hydrophobic bonding is not large. A possible stacking mode is postulated based on the complexation shifts and pi-electron charge distributions of caffeine and L tryptophan. PMID- 2313570 TI - Sensitive radioimmunoassay and enzyme-linked immunosorbent assay for the simultaneous determination of chloroquine and its metabolites in biological fluids. AB - Two new methods for the simultaneous determination of chloroquine and its two main metabolites (monodesethylchloroquine and bisdesethylchloroquine) in biological samples, radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), are described. Antiserum is produced in rabbits immunized with N-(2 carboxyethyl)desethylchloroquine:protein conjugate. Besides chloroquine, this antiserum recognizes with good affinity the two main metabolites, monodesethylchloroquine and bisdesethylchloroquine (70 and 40% of crossreaction, respectively). Amodiaquine cross reacts by 4.5%; cross reactions with monodesethylamodiaquine, bisdesethylamodiaquine, and other antimalarial drugs are less than 1%. No extraction step or sample preparation is required for either system. Sensitivity limits are, respectively, 0.70 nM (3 pg of chloroquine sulfate measured in 10 microL of plasma sample) for RIA, and 10 nM (22 pg of chloroquine sulfate measured in 5 microL of plasma sample) for ELISA. The interassay coefficients of variation are, respectively, less than 10 and less than 16% for RIA and ELISA in the range 14-410 nM (6-180 ng/mL). The results of both methods are well correlated (r = 0.97) and correlate with spectrophotometry (r = 0.98) and HPLC results (r = 0.93). Because of their high sensitivity, both methods can be used in the case of chloroquine poisoning and in the control of malaria prophylaxis and treatment. PMID- 2313571 TI - A model for alcohol-enhanced permeation through polydimethylsiloxane membranes. AB - In this study the influence of paraben concentration on flux from solution in 1 propanol through polydimethylsiloxane membranes was investigated. Alcohol was sorbed by the polymer membrane leading to changes in membrane dimensions and increased membrane capacity to contain paraben (partition coefficient). Diffusion coefficients were not significantly influenced by alcohol sorption. Flux was increased 5-30 fold over nonimbibed donors such as water and polyols. An increase in paraben concentration reduced alcohol activity, its uptake by the membrane, and consequently the partition coefficient of paraben. As a result, flux increased with paraben concentration, reached a peak, and then declined. Maximal membrane concentration involves a trade-off between alcohol-membrane interaction (solvent activity) and paraben concentration, and occurred at paraben concentrations in the range of 1.3 to 1.4 mmol/g. At equimolar concentrations, flux was highest for methylparaben and declined as the series was ascended. Differences in flux between parabens at a specified molar concentration were due only to differences in diffusivity. PMID- 2313572 TI - Comparative bioavailability of two tablet formulations of fluphenazine dihydrochloride in drug-free psychiatric patients. AB - The comparative bioavailability of a new tablet formulation of fluphenazine dihydrochloride (5 mg) and a reference product (fluphenazine dihydrochloride, Prolixin, 5 mg) was assessed in drug-free psychiatric patients. Twenty-six patients were initially entered in the study, of whom 22 completed the protocol. Each patient received the test (T) and the reference formulation (R) in a balanced two-way crossover design. Plasma concentrations of fluphenazine were monitored over a period of 48 h after drug administration using a sensitive HPLC method. One patient did not show any measurable plasma concentration for one formulation at any sampling time and, therefore, bioavailability was assessed in the remaining 21 patients. All pharmacokinetic parameters showed wide intersubject variation. The maximum plasma concentration (Cmax), time to Cmax, and area under the curve up to the last measurable concentration (AUClast0), infinity (AUCinfinity0), or truncated areas (such as AUC16(0), AUC24(0) were compared by analyses of variance and found not to be significantly different in each case across the formulations. Except for AUC24(0), AUC32(0), and AUC48(0), ANOVA of all other parameters showed a high power (greater than 80%) to detect a 20% difference in the mean value of each bioequivalence parameter between T and R. The two formulations were found to be bioequivalent in that confidence intervals of the mean values of AUCinfinity0, AUClast0, truncated AUCs, or Cmax for T:R ratios were, in each case, well within the acceptable range of 100 +/- 20%. PMID- 2313573 TI - Drug release from laminated polymeric films prepared from aqueous latexes. AB - Laminated films comprised of a drug-containing reservoir layer and a drug-free, rate-controlling membrane were prepared from aqueous latexes and investigated as an alternative drug delivery system to polymeric films cast from organic solvents. The reservoir layer was prepared by casting and drying the latex [copolymer of poly(ethylacrylate-methylmethacrylate) esters - Eudragit NE 30D (NE 30D)] containing the dissolved drugs (chlorpheniramine maleate, propranolol HCl, or salicylic acid). Monolithic solutions (salicylic acid-NE 30D) or dispersions (chlorpheniramine maleate or propranolol HCl-NE 30D) were formed, depending on the solubility of the drug in the polymer matrix. Zero-order drug release was achieved by laminating a second, drug-free latex film onto the reservoir layer. The rate-controlling membrane was either attached to, or cast directly onto the reservoir. The release rate was independent of loading for the monolithic dispersions, but dependent on loading for the monolithic solution. Release rates were enhanced by the addition of a hydrophilic polymer, hydroxypropyl methylcellulose, to the rate-controlling membrane. An inverse relationship was observed between the release rate and membrane thickness. The rate-controlling membrane, cast from organic polymer solutions, had a denser structure, resulting in slower drug release when compared with latex-cast laminates. PMID- 2313574 TI - Micellar modification of drug stability: analysis of the effect of hexadecyltrimethylammonium halides on the rate of degradation of cephaclor. AB - The intra- and intermolecular rates of degradation of cephaclor were determined with and without hexadecyltrimethylammonium bromide (CTABr). Micellar-derived spectral shifts were used to measure the association of the ionic forms as well as to determine the effect of CTABr on the apparent acid dissociation constant of the antibiotic. The rate of degradation of cephaclor increased with detergent and was salt sensitive. Micellar effects were analyzed quantitatively within the framework of the pseudophase ion exchange model. All experimental data were fitted to this model which was used to predict the combined effects of pH and detergent concentration. Micelles increased the rate of OH- attack on cephaclor; most of the effect was due to the concentration of reagents in the micellar pseudophase. The intramolecular degradation was catalyzed 25-fold by micelles, and a working hypothesis to rationalize this effect is proposed. The results demonstrate that quantitative analysis can be utilized to assess and predict effects of detergents on drug stability. PMID- 2313575 TI - Effect of the mode of croscarmellose sodium incorporation on tablet dissolution and friability. AB - A computer-optimized experimental design was used to study the effect of incorporating a "super disintegrant", croscarmellose sodium, intragranularly, extragranularly, or distributed equally between the two phases of a tablet in which a poorly soluble drug constituted at least 92.5% of the formulation. The results were analyzed by means of a general quadratic response surface model and suggest that tablets with the same total concentration of super disintegrant dissolve at a faster rate when the super disintegrant is included intragranularly. Tablet friability was not affected by the method of super disintegrant incorporation. PMID- 2313576 TI - Nefopam hydrochloride degradation kinetics in solution. AB - A stability-indicating reversed-phase high performance liquid chromatographic method was developed for the detection of nefopam hydrochloride and its degradation products under accelerated degradation conditions. The degradation kinetics of nefopam hydrochloride in aqueous solutions over a pH range of 1.18 to 9.94 at 90 +/- 0.2 degrees C was studied. The degradation of nefopam hydrochloride was found to follow apparent first-order kinetics. The pH-rate profile shows that maximum stability of nefopam hydrochloride was obtained at pH 5.2-5.4. No general acid or base catalysis from acetate, phosphate, or borate buffer species was observed. The catalytic rate constants on the protonated nefopam imposed by hydrogen ion and water was determined to be 7.16 X 10(-6) M-1 sec-1, and 4.54 X 10(-9) sec-1, respectively. The pKa of nefopam hydrochloride in aqueous solution was determined to be 8.98 +/- 0.33 (n = 3) at 25 +/- 0.2 degrees C by the spectrophotometric method. The catalytic rate constant of hydroxyl ion on the degradation of nefopam in either protonated or nonprotonated form was determined to be 6.63 X 10(-6) M-1 sec-1 and 4.06 X 10(-6) M-1 sec-1, respectively. A smaller effect of hydroxyl ion on the degradation of nonprotonated than on the degradation of protonated nefopam was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313577 TI - Degradation peptides of secretin after storage in acid and neutral aqueous solutions. AB - During the storage of secretin in acid and neutral aqueous solutions, five degradation peptides (A1, A2, A3, A4, A5) and one degradation peptide (N1) were produced, respectively. They were isolated in pure form by HPLC, and the intramolecular structures were studied by a combination of amino acid analysis, enzymatic digestions, HPLC, and Fab-mass spectroscopy. Although the degradation peptides are composed of the same amino acids as secretin after acid hydrolysis (except A1 and A4 which are cleavage products S16-27 and S4-27, respectively), reversed-phase HPLC analysis of their digestive fragments with trypsin and alpha chymotrypsin are different from those of secretin. By Fab-mass spectroscopy, the m/z values for the S1-6 fragments obtained from secretin, A2, and A3 were 663, 663, and 645, respectively. When S1-6 from A2 was treated with aminopeptidase M, a fragment obtained was identical with the synthetic beta-aspartyl3 S3-6, as determined by HPLC. The A2 and N1 peptides are completely the same based on various chemical analyses. The A3 peptide can also be rapidly degraded to secretin and beta-aspartyl3 secretin. Consequently, A1 and A4 are concluded to be the cleavage peptides of secretin, S16-27 and S4-27, respectively, A2 and N1 are concluded to be beta-aspartyl3 secretin, and A3 is concluded to be aspartoyl3 secretin. PMID- 2313578 TI - Structure-activity studies on organoselenium alkylating agents. AB - A variety of organoselenium alkylating agents were synthesized, using 2 hydroxyethyl and 3-hydroxypropyl selenocyanate intermediates, and studied to determine their chemical reactivities with 4-(4-nitrobenzyl)pyridine (NBP) and cytotoxicities against CCRF-CEM, L1210/0, and L1210/L-PAM cells. The comparison between the 2-chloroethyl sulfides and selenides 1-4 revealed the markedly enhanced nucleophilicity of selenium (Se) over sulfur (S) by two or more orders of magnitude. This finding indicates that a major consideration in the design of antitumor alkylating organoselenides is the reactivity of selenium. A Taft plot of the experimental first-order rate constant, knbp, and sigma* in a series of 2 chloroethylseleno compounds gave a slope of -1.73 (rho*), with the exception of 2 chloroethyl 2-nitrophenyl selenide (10). The anomalous behavior of 10 is explained in terms of the ortho-nitro stabilization effect directly interacting with the selenium atom of ethyleneselenonium ion to form a 5-membered cyclic intermediate. In the same series, a 5000-fold difference in alkylating reactivity offered only a sixfold variation in cytotoxicity against CCRF-CEM cells. Increasing the alkylating chain length from ethlene to propylene units markedly reduced alkylating reactivities. In the CH3Se(CH2)n Cl series, 16 (n = 3) was 1.5 X 10(5) times slower than 2 (n = 2) in NBP alkylation, revealing that 3-chloro-n propyl selenides are not chemically reactive enough to be biological alkylating agents despite the presence of the highly nucleophilic selenium atom. Replacement of chloride with mesylate in 3-substituted propyl selenides, such as 17 and 20, restored desirable reactivities and cytotoxicities. PMID- 2313579 TI - Hydrolysis of nipecotic acid phenyl esters. AB - The synthesis and anticonvulsant activity of nipecotic acid esters (1a-1f) have been previously reported. It was thought that these prodrug esters underwent hydrolytic conversion to 1 which inhibited GABA uptake, and that both 1 and an intact ester may have caused inhibition of GABA uptake which resulted in the anticonvulsant activity. There is, however, no stability data available to help evaluate these effects. We have determined degradation half-lives (t 1/2) of these phenyl esters dissolved in 10% serum solution or in pH 7.4 buffer (ionic strength = 0.25 adjusted with KCl) at 37 degrees C by monitoring the appearance of a phenolic compound for a period of 12 h with an HPLC method. Utilizing a published method, in vitro [14C]GABA uptake was measured. Results show that the hydrolysis rate in 10% serum solution was faster than that in buffer solution and that half-lives varied between 0.20 and 3.84 h. The uptake inhibition varied between 8.2 and 41.7% at 0.02 mM concentration, and percent GABA uptake inhibition correlated with log t 1/2 (r = -0.9827, p = 0.00045, based on a t test). Our data suggest that at concentrations ranging from 0.02 to 1 mM, inhibition of GABA uptake is mainly due to 1 formed after hydrolysis of 1a-1f. PMID- 2313581 TI - Direct determination of protein binding of phenytoin in serum by high-performance liquid chromatography. AB - A reliable, routine method has been developed which speeds and simplifies the determination of free phenytoin levels in serum. The free fraction of the drug was determined by a single direct injection of serum (350 microL) into a high performance liquid chromatography (HPLC) system. The mobile phase was a mixture of isopropanol (0.5%) and pH 7.4 phosphate buffer. An internal surface reversed phase silica column, the Pinkerton column, was used with a flow rate of 1.0 mL/min at ambient temperature, and the wavelength was set at 254 nm. The resolution of free and bound phenytoin peaks was affected by the percentage of isopropanol, the serum volume injected, and the protein concentration in the sample. The concentrations of free and bound drug agreed well with those determined by the conventional ultrafiltration method (MPS-1). The determination of protein binding by HPLC appears to be a satisfactory method for routine therapeutic drug monitoring. The factors affecting the binding and chromatographic separation and the application of this method for clinical use are discussed. PMID- 2313580 TI - Alkylation of 6-mercaptopurine (6-MP) with N-alkyl-N-alkoxycarbonylaminomethyl chlorides: S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP prodrug structure effect on the dermal delivery of 6-MP. AB - The S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP (6-CARB-6-MP) prodrugs 5-20 were synthesized from the reaction of 6-MP with N-alkyl-N alkyoxycarbonylaminomethyl chlorides (4) in dimethyl sulfoxide in overall yields of 5-62%, depending on the N-alkyl and the alkoxy groups involved. The derivatives were fully characterized by spectral and microanalyses. The assignment of the substitution pattern as S6-alkyl was based on comparisons of the UV, 1H NMR and 13C NMR spectra with model compounds. A S6, 9-bis-alkyl derivative was obtained from the reaction of 2 equivalents of 4 with 6-MP but the product was unstable and decomposed on standing to a 9-alkyl derivative. The 6 CARB-6-MP prodrugs reverted to 6-MP in water by an SN1-type mechanism involving unimolecular charge separation in the transition state of the rate determining step. There was no effect of dermal enzymes on the rate of hydrolysis. The solubilities in isopropyl myristate (IPM) for all of the 6-CARB-6-MP prodrugs were significantly greater than the solubility of 6-MP in IPM but only one prodrug (5) was apparently even as soluble as 6-MP in water. Selected 6-CARB-6-MP prodrugs were examined in diffusion cell experiments. Only the N-methyl-N methoxycarbonyl derivative 5 gave a steady-state rate of delivery of 6-MP from IPM that was significantly greater than the steady-state rate of delivery of 6-MP from 6-MP in IPM. All the other derivatives gave steady-state rates of delivery of 6-MP from IPM that were either not significantly different, or were significantly lower than the rate obtained from 6-MP in IPM. In all cases, the effect of the 6-CARB-6-MP:IPM suspensions on the permeability of the skin, as determined by the second application flux of theophylline:propylene glycol, was of the same magnitude as the effect of IPM alone. PMID- 2313582 TI - A study of the electrokinetic and stability properties of nitrofurantoin suspensions. I: Electrokinetics. AB - An experimental investigation is described of the electrokinetic properties of nitrofurantoin. The experiments are based on measurements of electrophoretic mobility in suspensions of this drug and the calculation of its zeta potential (zeta) following two different procedures. A simple mechanism is proposed for explaining the sign of the surface charge of nitrofurantoin and its increase with the pH of the medium. The effect on zeta of changes in the concentration of NaCl, CaCl2, or AlCl3 is studied for different pH values of the suspensions. The behavior of zeta in the presence of NaCl shows evidence of Cl- adsorption on the particles, especially at low electrolyte concentrations. The AlCl3 salt was capable of reversing the sign of the surface charge, changing it to positive when a given, pH-dependent concentration was added to the suspension. The effect of this salt on zeta for different pH values was probably due to the hydrolysis of the cation Al3+. A significant increase of the negative surface charge was observed when a small amount (0.1%) of a synthetic polymer, Carbopol 934, was present in NaCl or AlCl3 systems. This appears to indicate that the large polymer molecules adsorb on nitrofurantoin particles as part of their stabilizing mechanism. PMID- 2313583 TI - Comments on hydrophile--lipophile balance systems. PMID- 2313584 TI - Corrigible error correction. PMID- 2313585 TI - Use of 1-anilino-8-naphthalene sulfonate as a fluorescent probe in the investigation of drug interactions with human alpha-1-acid glycoprotein and serum albumin. AB - We report a rapid method for the characterization of the human serum albumin (HSA) and alpha-1-acid glycoprotein (AAG) interactions with drugs. The binding of 1-anilino-8-naphthalene sulfonate (ANS) to AAG and HSA was measured by fluorescence spectroscopy. Fluorescence data indicated that ANS was bound tightly to at least one site on AAG, with an affinity constant of 1.35 x 10(6) M-1. The fluorescence of an ANS:AAG complex was quenched by the binding of various drugs. Fluorescence quenching of the HSA:ANS complex showed a single site with an affinity constant of 0.72 x 10(6) M-1. The interaction of AAG and HSA with ANS or other drugs was also studied by comparative equilibrium dialysis. [14C]Pipequaline was used as an AAG and HSA site marker. [14C]Pipequaline seems to share sites I (azapropazone) and II (diazepam and ibuprofen) of HSA. However, high concentrations of warfarin were unable to displace [14C]pipequaline. On the other hand, it was shown that palmitic acid decreased, whereas bilirubin increased the pipequaline binding. PMID- 2313587 TI - Phorbol-12,13-dibutyrate-induced vasoconstriction in vivo: characterization of response in genetic hypertension. AB - To assess the role of protein kinase C (PKC) in the control of vessel tone in vivo in genetic hypertension, the vascular effects of phorbol-12,13-dibutyrate (PDBu), a PKC activator, was measured in the autoperfused hindlimb of reserpinized spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). PDBu infusion (1-3000 ng/kg/min) into the hindlimb elevated perfusion pressure in a dose-related manner. Vasoconstriction response characteristics (latency, T1/2 to peak effect, decay of effect) of PDBu were significantly longer (2- to 10-fold) than that produced by membrane receptor agonists; phenylephrine, SKF 89748, a lipophilic alpha-1 agonist, angiotensin II and 5-hydroxytryptamine. The tonic vasoconstriction induced by PDBu was not antagonized by prazosin, rauwolscine, cyproheptadine, [Sar1lle8]-angiotensin II but was inhibited reversibly by microbial PKC-inhibitors, K252a and staurosporine at concentrations (1.56-2.8 micrograms/kg/min) which did not block vasoconstriction by phenylephrine or 5-hydroxytryptamine. The EC50 for PDBu was identical in SHR and WKY. However, the maximal response to PDBu was significantly greater in SHR compared to WKY. Staurosporine lowered mean arterial pressure equally in SHR (20%) and WKY (17%) but reduced perfusion pressure in SHR (13%) to a slightly greater extent than in WKY (5%). Unlike the in vivo response, aortic rings removed from SHR were more sensitive to cumulative doses of PDBu than rings from WKY. It is concluded that PDBu-vasoconstriction in vivo is mediated largely through activation of PKC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313586 TI - Castration-induced changes in the response of the hypothalamic-pituitary axis to alcohol in the male rat. AB - In an attempt to determine the direct effects of alcohol on the hypothalamic pituitary aspect of the hypothalamic-pituitary-gonadal axis, we examined the effects of alcohol on serum luteinizing hormone (LH) levels in the normal and testosterone-depleted castrated male rat. We found that within several days after castration (2-4 days) alcohol, at low to moderate doses, was only modestly effective in suppressing serum LH levels, whereas in sham-operated controls it was maximally effective at all doses tested. Surprisingly, at very high doses (4 6 g/kg), alcohol not only did not depress serum LH levels in long-term castrated rats, but elevated them by 2- to 4-fold when compared to saline-injected controls. The loss of sensitivity of the hypothalamic-pituitary axis to alcohol observed in castrated rats appeared to be selective, inasmuch as the mortality rate at high doses of alcohol was significantly (P less than .01) greater in castrated rats, when compared to sham-operated controls, and other measures of central nervous system impairment were equivalent in both groups. At the present time, it is difficult to explain this biphasic effect of alcohol on serum LH in the castrated animal, but our results are consistent with the hypothesis that the effects of alcohol on gonadotropin release may be dependent to a significant degree on the steroid milieu at the time of the experiments. PMID- 2313588 TI - Mouse thiopurine methyltransferase pharmacogenetics: correlation of immunoreactive protein and enzymatic activity. AB - Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds including thiopurine drugs such as 6 mercaptopurine. Genetic polymorphisms control levels of TPMT enzymatic activity in both humans and inbred mice. AKR/J (AK) and C57BL/6J (B6) mice have genetically low, whereas DBA/2J (D2) mice have genetically high levels of hepatic TPMT activity. No biochemical differences in TPMT have been detected among these strains of mouse. That observation increased the possibility that inherited variations in TPMT activity in these animals might be correlated with variations in the quantity of enzyme protein, just as they are in human tissue. Polyclonal rabbit antibodies to partially purified mouse liver TPMT were used to develop an immunoprecipitation assay for the enzyme. The volume of antiserum required to titrate 50% of the TPMT activity (antibody dose 50 or AD50) was used as a measure of immunoreactive TPMT protein. When AD50 values were measured in hepatic preparations from AK, B6 and D2 mice, inherited variations in levels of hepatic TPMT activity in these inbred strains were correlated directly with the quantity of TPMT immunoreactive protein. Identical results were obtained with F1 hybrids derived from AK X D2 and B6 X D2 matings. Finally, TPMT enzyme activity and immunoreactive protein levels were also correlated directly in hepatic preparations from six recombinant inbred (RI) strains derived from AK X D2 (AKXD) and six RI strains derived from B6 X D2 (BXD) matings. In neither AKXD nor BXD RI mice were there significant differences between TPMT homospecific activities in animals homozygous for the alleles for high or low TPMT activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313589 TI - Synthesis and identification of the N-glucuronides of norgallopamil and norverapamil, unusual metabolites of gallopamil and verapamil. AB - N-Glucuronides of norgallopamil and norverapamil were found as biliary metabolites after administering the corresponding tertiary amines, gallopamil and verapamil, to rats. The structures of these unusual metabolites were established by comparison with spectral data of synthesized authentic standards and by enzymic hydrolysis of the conjugates. The N-glucuronide standards were synthesized by coupling the secondary amines to either glucuronic acid or to methyl tetra-O-acetyl-beta-D-glucopyranuronate. On i.p. dosing of rats with gallopamil or verapamil, 13 and 2% of the dose, respectively, appeared in the bile as the N-glucuronide of the secondary amine metabolite over an 8-hr period. Administration of norgallopamil resulted in approximately 25% of the dose being excreted as N-glucuronide conjugate in the bile. Substantially more of the S- than R-enantiomer of both gallopamil and verapamil was converted to the corresponding secondary amine N-glucuronide. The observed high S/R ratios suggest enantio-selectivity in this pathway could contribute to the observed stereoselectivity in other routes of metabolism of the parent tertiary amines. PMID- 2313590 TI - Lethality of morphine in mice infected with Toxoplasma gondii. AB - Opiates modulate a variety of immune responses. We investigated the effect of morphine on the pathogenesis of an acute Toxoplasma gondii infection. Repeated s.c. injections with morphine sulfate (300 mg/kg) every 36 hr addicted mice and increased markedly the mortality of mice infected with an avirulent strain of T. gondii (86%) vs. 0% mortality in addicted and control mice, respectively, P less than .001). However, a single challenge with morphine (300 mg/kg) also markedly (P less than .001) increased mortality (94%) of infected mice when the morphine was administered at day 13 postinfection; susceptibility to the lethal effect was not observed until day 9 postinfection, a time when immune reactivity was evident (i.e., 3- to 4-fold splenic enlargement). This lethal effect was attenuated by pretreatment with naltrexone, suggesting involvement of an opiate receptor mechanism. Sulfadiazine treatment abrogated morphine-induced mortality, indicating a prerequisite of an active infectious state. These findings suggest that immune activation by T. gondii infection plays a critical role in morphine induced mortality in this murine model. PMID- 2313591 TI - Phencyclidine blocks voltage-dependent potassium currents in murine thymocytes. AB - We investigated the effect of phencyclidine (PCP) on the voltage-dependent K+ current in whole cell recordings from murine thymocytes. PCP caused a dramatic, reversible and dose-dependent decrease of the current. An analysis of the dose response relationship suggests a single site of action for PCP with an IC50 of 4.7 microM. Dextrorphan and naloxone also inhibited the current, although their effects were of a lower magnitude than those of PCP. Neither 10 microM dextrorphan nor 100 microM naloxone antagonized the inhibitory action of 10 microM PCP. The analysis of the dose-response curve for PCP in presence of 100 microM naloxone suggested that the two drugs act at the same site. We also investigated the effect of morphine on the K+ current. Morphine, in concentrations up to 100 microM, inhibited the K+ current less than dextrorphan or PCP. The kinetics and voltage dependence of the currents in the presence of morphine suggest that it interacts with a different site or different conformation of the channel than the other three compounds. Our findings show that certain opioids can act on thymocytes through a system completely different from the typical opioid receptors. PMID- 2313593 TI - Altered hepatobiliary disposition of acetaminophen metabolites after phenobarbital pretreatment and renal ligation: evidence for impaired biliary excretion and a diffusional barrier. AB - The effects of phenobarbital (Pb)-pretreatment and bilateral renal ligation on the disposition of acetaminophen, acetaminophen glucuronide (AG) and acetaminophen sulfate (AS) were examined in serum, bile and urine of rats. Pb pretreatment significantly decreased the percentage of the acetaminophen dose (100 mg/kg) excreted in bile as the glucuronide and sulfate conjugates in rats with intact kidneys [AG (0.94% vs. 6.49%); AS (1.41% vs. 4.19%)] and in renal ligated rats [AG (2.22% vs. 7.71%); AS (6.12% vs. 9.13%)], compared to vehicle pretreated controls. Decreased biliary recovery of AG occurred despite a Pb induced increase in the fraction of the acetaminophen dose converted to AG. Similarly, biliary recovery of AS was reduced further than expected based on Pb associated decreases in the fraction of the acetaminophen dose converted to AS. These observations suggest that the hepatobiliary disposition of AG and AS was altered at multiple sites due to 1) direct interactions with Pb (or a Pb metabolite) and/or 2) metabolic induction by Pb. Renal ligation shifted the metabolic pathway toward sulfation, with a subsequent increase in biliary recovery of AS. However, renal ligation did not alter the percentage of the dose excreted as AG in bile despite a marked elevation in AG serum concentrations. Furthermore, biliary excretion rate vs. time profiles of AG and AS in renal ligated rats exhibited a terminal half-life exceeding that of acetaminophen in serum. These data provide evidence that diffusional barriers between blood and hepatocytes influence the hepatic disposition and routes of elimination of polar metabolites such as AG and AS. PMID- 2313592 TI - Effects of nerve stimulation on ion transport in mouse jejunum: responses to Veratrum alkaloids. AB - Veratrum alkaloids were used to examine the effect of neural stimulation on intestinal ion transport in full-thickness (intact) and serosally stripped (mucosal) preparations of mouse jejunum. When applied to the serosal media of mucosal preparations, veratrine or veratridine evoked a biphasic increase in transmural potential difference and short-circuit current, consisting of phasic and tonic increases of both bioelectric parameters without a change of tissue conductance; these responses were blocked by pretreatment with tetrodotoxin, but unaffected by pretreatment with atropine, naloxone or yohimbine. In ion flux experiments, neural stimulation of mucosal tissues produced changes of unidirectional fluxes that corresponded with an increase in net Cl- secretion and a reduction of net Na+ absorption, supporting a net secretory role for neurons that were associated with the intestinal mucosa. In intact jejunal preparations, neural stimulation by veratrine or veratridine caused a tetrodotoxin-sensitive reduction of basal transmural potential difference and short-circuit current and a significant increase of tissue conductance. Flux studies on intact tissues failed to reveal the ionic basis for the effects of nerve stimulation by veratridine in these tissues. Nonetheless, the neurally evoked reduction of short circuit current was attenuated by yohimbine pretreatment, but unaffected by naloxone or atropine, suggesting an involvement of alpha-2 adrenoceptors in the mediation of this effect. These findings demonstrate the existence of endogenous neurotransmitter systems that play opposing roles in the regulation of mucosal ion transport in the small intestine of the mouse. PMID- 2313594 TI - Mechanism of angiotensin II action on proximal tubular transport. AB - Our previous studies have shown that a low dose of angiotensin II (Ang II) stimulates fluid and bicarbonate absorption from the apical side of rat proximal tubule (PCT). These effects can be blocked by Ang II antagonist, (Sar1, Ile8)Ang II. The cellular mechanism underlying Ang II action, however, remained unclear. Thus, this study was designed to investigate the possible role of phosphoinositide turnover in mediating this action of angiotensin. Rat PCT was perfused in vivo with Ringer's solution containing [3H]inulin as a volume marker. Bicarbonate flux (JHCO3) was determined by total CO2 changes between the collected fluid and the original perfusate as analyzed by microcalorimetry. Luminal perfusion of 10(-11) M Ang II stimulated both JHCO3 and fluid reabsorption. These effects could be blocked by 10(-3) M amiloride and 10(-5) M ethylisopropylamiloride. Luminal perfusion of 4 beta-phorbol-12-myristate-13 acetate (10(-8) M) also stimulated both fluid reabsorption and JHCO3. These effects could also be blocked by amiloride and ethylisopropylamiloride. When both Ang II (10(-11) M) and 4 beta-phorbol-12-myristate-13-acetate (10(-8) M) were perfused together, the stimulatory effects on fluid reabsorption and JHCO3 were not additive. These results suggest that Ang II interacts with its receptors on the apical membrane leading to modulation of the Na-H exchange mechanism in PCT. The phosphoinositide turnover may play an important role in the Ang II action on PCT transport. PMID- 2313595 TI - Alteration of thermoregulatory set point with opioid agonists. AB - This paper focuses on the behavioral thermoregulatory effects of i.c.v. administration of [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO), cyclic [D-Pen2,D Pen5]enkephalin (DPDPE) and U-50,488H, selective agonists for the mu, delta and kappa opioid receptors, respectively. Rats were tested in a thermally graded tunnel (thermocline) which allowed for simultaneous measurement of body temperature, ambient temperature selection and general ambulatory activity levels. DAMGO (0.3 micrograms) caused an increase in body temperature which was facilitated by the selection of a warm ambient temperature. Both DPDPE (30 micrograms) and U-50,488H (100 micrograms) caused decreases in body temperature which were accompanied by a selection of a cool ambient temperature. In each case there was evidence for a regulated change in body temperature, with DAMGO increasing thermoregulatory set point and DPDPE and U-50,488H decreasing set point. DAMGO and U-50,488H produced a depression of activity levels for the first 15 min after injection. DAMGO and DPDPE produced increases in activity levels which peaked after body temperature had returned toward base-line levels. These data characterize further the differentiable profiles of physiological effects produced by these three compounds. The central modulation of the control of body temperature by these opioid receptor agonists may reflect a role of endogenous opioids in thermoregulatory control. PMID- 2313596 TI - Nonpeptide angiotensin II receptor antagonists. VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent. AB - 2-n-Butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazole-5-yl)biphenyl-4-y l) methyl]imidazole, potassium salt (DuP 753) is a potent, p.o. active antihypertensive agent exerting its action by specific blockade of angiotensin II receptors. It inhibited the specific binding of labeled angiotensin II to its receptor sites in rat adrenal cortical membranes and in cultured rat smooth muscle cells with IC50 values of 19 and 20 X 10(-9) M, respectively. Functional antagonism was demonstrated by its blockage of angiotensin II (3 X 10(-8) M) induced 45Ca++ efflux in rat aortic smooth muscle cells with an IC50 of 2 X 10( 8) M. In rabbit aorta, DuP 753 antagonized the contractile response to angiotensin II competitively with a pA2 value of 8.48 but had no effect on the responses induced by norepinephrine or KCl. In both in vitro and in vivo assays, no partial agonistic effect was detected even with concentrations of up to 10(-5) M. In addition, this agent (10(-5) or 10(-4) M) exhibited no direct effect on converting enzyme (rabbit lung) or renin (rat plasma). These data demonstrate that DuP 753, is a potent and highly specific angiotensin II receptor antagonist. This agent may be a useful experimental or therapeutic tool for interference with the renin-angiotensin system in health and diseases. PMID- 2313597 TI - Pharmacodynamics of local heparin infusion in a canine renal allograft model. AB - Inasmuch as heparin has demonstrated immunosuppressive activity in vivo and in vitro, we utilized a canine renal transplant model to estimate the first-pass extraction of heparin during renal artery infusion and to examine the effect of regional heparin delivery on the histologic features of rejection and allograft survival. Four autotransplanted mongrel dogs with programmable, implantable pump/catheter systems received a continuous intrarenal heparin infusion which was increased daily in stepwise fashion. Activated coagulation time (ACT) rose linearly with local heparin dose, indicating that heparin clearance remained constant over the dosage range studied. Comparison of these ACT values with those measured during same-dose i.v. infusion and those predicted from i.v. bolus studies revealed that there was little or no first-pass renal extraction of heparin by the transplanted kidney. In nine allografted dogs, the heparin infusion rate was adjusted according to daily ACT to maximize local heparin delivery but still maintain the ACT close to 125% of base line. There was no difference in overall survival between the heparin-treated dogs and a group of 14 untreated controls, and vascular rejection was significantly more intense in the heparin-treated animals. We conclude that intrarenal dosing of heparin to the point of producing systemic anticoagulation is limited by failure of the transplanted kidney to eliminate drug and does not prolong canine renal allograft survival. PMID- 2313598 TI - Muscarinic receptor blockade increases basal acetylcholine release from striatal slices. AB - The main objective of these studies was to determine whether the basal release of acetylcholine (ACh) from brain slices was subject to modulation by muscarinic receptor blockade. Incubation of striatal slices with the muscarinic antagonist atropine increased ACh release in a concentration-dependent manner with a maximal effect (1.4-1.8 times control release) achieved with 0.1 to 1.0 microM. In contrast, ACh release from hippocampal slices was unaltered by any concentration of atropine tested, indicating that the basal release of neurotransmitter from striatum, but not hippocampus, was subject to modulation by muscarinic receptor blockade. Incubation of striatal slices with 1 microM tetrodotoxin or removal of Ca++ from the medium decreased the basal release of ACh by 20% and abolished the atropine-induced release of ACh; neurotransmitter release from hippocampal slices was unaltered by tetrodotoxin. Thus, part of the basal release of ACh from striatal slices is a consequence of the intrinsic impulse activity of cholinergic neurons and it is this component of release that is atropine-sensitive. Oxotremorine was unable to antagonize the atropine-induced release of ACh, even with concentrations 100 times that of atropine, whereas pirenzepine increased ACh release and, like that of atropine, the effect of pirenzepine was sensitive to tetrodotoxin and resistant to oxotremorine. These results indicate that a component of basal ACh release from striatal slices is subject to modulation by a receptor that is sensitive to atropine and pirenzepine, but not to oxotremorine, suggesting that this site differs from the nerve terminal muscarinic autoreceptor. PMID- 2313599 TI - Direct binding and functional studies on muscarinic cholinoceptors in porcine coronary artery. AB - The muscarinic cholinoceptors in porcine coronary artery were identified and characterized by a binding assay using (-)-[3H]quinuclidinyl benzilate (QNB) and also by pharmacological method. Specific (-)-[3H]QNB binding in the coronary artery was saturable and of high affinity (Kd = 0.08 nM), and it showed a pharmacological specificity as well as stereoselectivity which characterized muscarinic receptors. Muscarinic antagonists competed with the (-)-[3H]QNB binding in order: nonlabeled QNB greater than dexetimide greater than atropine greater than pirenzepine greater than AF-DX 116 greater than levetimide greater than gallamine. Dexetimide was approximately 2000 times as potent as levetimide. The potencies (pKi) of these muscarinic antagonists in competing for (-)-[3H]QNB binding sites in porcine coronary artery correlated well with their pharmacological potencies (pA2 for antagonistic effect of acetylcholine-induced contraction of coronary artery). The decrease in the (-)-[3H]QNB binding by atropine and pirenzepine was due to a reduction in the apparent affinity with little change in the number of maximal binding sites, suggesting a competitive antagonism. Specific (-)-[3H]QNB binding (Kd and maximal number of binding sites) in porcine coronary artery was not changed by the removal of endothelium. We conclude: 1) (-)-[3H]QNB selectively labels the physiologically relevant muscarinic receptors in porcine coronary artery and 2) the majority of these receptors is localized on vascular smooth muscles and the receptors mediate the acetylcholine-induced contractile response of coronary artery. PMID- 2313600 TI - Formation of inositol polyphosphates in airway smooth muscle after muscarinic receptor stimulation. AB - The effect of muscarinic-receptor stimulation on [3H]inositol mono-, bis-, tris- and tetrakisphosphate (InsP1, InsP2, InsP3 and InsP4) accumulation was examined in bovine tracheal smooth muscle slices prelabeled with myo-[3H]inositol. Carbachol (0.1 mM) caused a rapid increase in [3H]InsP3 and [3H]InsP2 followed by delayed increases in [3H]InsP1 and [3H]InsP4 accumulation. Analysis of the [3H]InsP3 isomers by HPLC showed an immediate although transient increase in [3H]Ins(1,4,5)P3 with a progressive and sustained accumulation of [3H]Ins(1,3,4)P3. [3H]Ins(1,3,4)P3 was confirmed as the predominant (greater than 80%) [3H]InsP3 isomer present at 1 and 30 min using an enzymatic method which causes selective hydrolysis of Ins(1,3,4)P3. Lithium enhanced markedly the carbachol-stimulated accumulation of [3H]InsP1 and [3H]InsP2 with a lower potency than that observed in other tissues but had no significant influence on [3H]InsP3 or [3H]InsP4 values. These data support a role for Ins(1,4,5)P3 in initiating airway smooth muscle contraction and indicate the importance of the Ins(1,3,4,5)P4/Ins(1,3,4)P4 pathway in this tissue. PMID- 2313601 TI - Urate and p-aminohippurate transport in the brush border membrane of the pig kidney. AB - The transport of urate and p-aminohippurate (PAH) across the pig renal brush border membrane was investigated using membrane vesicles. Compared to a pH equilibrium condition (pHin = 7.4; pHout = 7.4), an outwardly directed OH- gradient (pHin = 7.4; pHout = 5.8) stimulated markedly both lactate and pyrazinoate uptake with overshoots exceeding 2 times that of the steady state. In contrast, neither OH-/urate nor OH-/PAH exchange could be demonstrated. An outwardly directed Cl- gradient (Cl-in = 100 mM; Cl-out = 16.7 mM) increased 2.6 fold 15-sec PAH uptake compared to Cl- equilibrium (Cl-in = Cl-out = 100 mM) but this stimulation was due solely to an effect of membrane potential. Creation of an electropositive intravesicular space, by imposing an inwardly directed K+ gradient (K+in = 0 mM; K+out = 100 mM) in the presence of valinomycin, was very effective to drive uphill PAH and urate accumulation compared to the control condition (no valinomycin). Four-second potential-stimulated PAH uptake was saturable (Km, 0.8 mM; Vmax, 1.7 nmol/mg of protein x 4 sec). Different organic anions cis-inhibited both 4-sec potential-stimulated PAH and urate uptakes in a similar fashion. PAH and urate, moreover, decreased each other's accumulation. In countertransport experiments, PAH and urate uptakes were not significantly stimulated by trans-unlabeled substrate. These results are consistent with the presence, in the pig renal brush border membrane, of a mediated secretory pathway common for urate and PAH, which could be facilitated by the potential difference existing in vivo across the luminal membrane of the proximal tubule. PMID- 2313602 TI - Transport mechanisms of bestatin in rabbit intestinal brush-border membranes: role of H+/dipeptide cotransport system. AB - Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine], a potent inhibitor of aminopeptidase B and leucine aminopeptidase, enhances the immune response to activate the defense mechanism of the living organism and suppresses the growth and metastasis of cancer. Bestatin has been effectively used by p.o. administration, but the mechanisms of intestinal absorption remain to be solved. The present study was undertaken to examine whether bestatin, a dipeptide containing an unusual amino acid, is transported via dipeptide carriers in intestinal brush-border membranes, by using cephradine as a probe for the H+/dipeptide cotransport system. The initial uptake of cephradine in the presence or absence of an inward H+ gradient, driving force, was inhibited by bestatin and this inhibition occurred in a competitive manner (Ki = 0.47 mM). The uptake of cephradine was stimulated by the countertransport effect of bestatin, the definitive criterion for ascertaining a common transport system. These findings indicate that bestatin, as well as cephradine and other p.o. cephalosporins, can be transported via dipeptide carriers in intestinal brush-border membranes. PMID- 2313603 TI - Interaction of chronic ethanol consumption and aging on brain muscarinic cholinergic receptors. AB - It has been proposed that ethanol and aging may interact synergistically to impair brain function through effects on central muscarinic receptors. Previous studies have investigated the effect of either chronic ethanol treatment or aging, but not both factors simultaneously, on brain muscarinic receptors. We have studied brain muscarinic receptors in animals treated with ethanol for up to 25 months. Ethanol consumption for 3 and 9 months resulted in increased density of quinuclidinyl benzilate (QNB) binding sites in cortex, coinciding with an increase in high-affinity pirenzepine binding sites and low-affinity carbachol binding sites. Upregulation of QNB binding sites in striatum and hippocampus became obvious after further ethanol treatment (15 and 21 months, respectively). Affinity of QNB binding sites and carbachol binding sites was not altered by ethanol treatment. However, there was an ethanol-related decrease in affinity of low-affinity pirenzepine binding sites in cerebral cortex. Density of QNB binding sites and low-affinity pirenzepine binding sites decreased with age in three brain areas investigated. There were age-related changes in receptor affinity in hippocampus and striatum, but not in cortex. Ethanol-related upregulation of muscarinic receptors was superimposed on age-related loss of receptors. We conclude that acceleration of the aging process associated with ethanol abuse is unlikely to be explained on the basis of alterations in receptor density or affinity. PMID- 2313604 TI - Lamb ductus venosus: evidence of a cytochrome P-450 mechanism in its contractile tension. AB - We have recently shown that a cytochrome P-450-based mechanism is important for the generation of contractile tension by the ductus arteriosus and have now examined whether the same mechanism operates in the ductus venosus. Carbon monoxide (CO/O2 ratio, 0.27) and cytochrome P-450 inhibitors [metyrapone; 4 phenylimidazole; 14-isocyano, 15-(methoxymethyleneoxy)-5Z,8Z,11Z- eicosatrienoic acid; alpha-naphthoflavone] were tested in vitro on the ductus venosus sphincter from mature fetal lambs. Each preparation was precontracted with indomethacin (2.8 x 10(-6) M). Carbon monoxide completely relaxed the ductus, and its action was reversed by illumination with monochromatic light. Peak photocontraction occurred at 450 nm. With the exception of alpha-naphthoflavone, all cytochrome P 450 inhibitors were also relaxant agents. Alpha-naphthoflavone (the sole type I inhibitor tested) produced instead a modest contraction that was often transient. Relaxation brought about by both carbon monoxide and drugs was fully reversed by the thromboxane A2 analog 9,11-epithio-11,12-methano-thromboxane A2 and by excess potassium (55 mM). Carbon monoxide was equally effective in the intact ductus and the ductus denuded of endothelium, whereas cytochrome P-450 inhibitors were marginally less effective in the latter preparation. These findings indicate that the ductus venosus sphincter, like the ductus arteriosus, relies on an intramural cytochrome P-450 mechanism to develop its contractile tone. The actual constrictor remains to be characterized in both vessels. PMID- 2313605 TI - Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. AB - Fourty-three patients with oral mucosal lesions were divided into 3 groups based on the relationship between lesions and amalgam restorations. Group I consisted of patients with contact lesions confined to mucosal areas in contact with amalgam fillings. Group II patients had lichen planus lesions exceeding the area of contact with an amalgam filling and Group III comprised patients with lichen planus lesions without relation to amalgam fillings. Biopsies were embedded in epon and subjected to autometallography in order to demonstrate a possible accumulation of mercury in the affected mucosa. In 20 our of 21 patients in Group I, 4 of 11 patients in Group II and 4 of 11 patients in Group III, mercury was found in the lysosomes of macrophages and fibroblasts. In Group I the number of cells loaded with mercury was much higher than in Group II and in particular Group III. In the latter groups autometallographically demonstrated mercury was found almost exclusively in macrophages. Nineteen biopsies taken from patients with normal mucosa served as controls. Ten had occlusal (Group IV) and seven buccal fillings (Group V). The biopsies from the latter group were taken from areas opposing amalgam restorations. Two patients had no amalgam fillings (Group VI). The histochemical technique showed that three biopsies in Group IV (occlusal fillings only) and two in Group V (opposing buccal fillings) contained traces of mercury in the juxtaepithelial connective tissue. The silver enhanced mercury was found in macrophages. The two controls (Group VI) without amalgam fillings were devoid of precipitates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313606 TI - Relationship of abnormalities in dental and skeletal development in the osteopetrotic (os) rabbit. AB - Osteopetrosis is a metabolic bone disease characterized by reduced bone resorption of heterogenous cause. The rabbit mutation is lethal and exhibits ultrastructural aberrations in osteoclasts and osteoblasts together with hypocalcemia, hypophosphatemia and failure to be cured by bone marrow transplantation. We have studied dental abnormalities in mutants from birth to 3 wk using radiographic, cytologic and autoradiographic methods. Radiographs show hypoplasia of most teeth in mutants. The maxillary incisor is smaller and more curved and the mandibular incisor thin and straight compared to normal littermates. The first 3 molars in both arches are unerupted and of distorted shape while the last 2 are less affected. Microscopically areas of ankylosis of mutant incisors and the first 3 molars were commonly encountered even at birth. Osteoclasts were numerous. Autoradiograms of 3H-proline incorporation showed strong periosteal and weak endosteal labeling of bone in both mutants and normal littermates. Dentin labeling in mutant incisors and molars was not less than that in normal rabbits and sites of ankylosis in mutants exhibited labeling. These data indicate that osteopetrotic rabbits exhibit major aberrations in shape and eruption of incisors and most molars and that these effects are not due to lack of dentin formation. Early ankylosis, perhaps secondary to congenital reduction of bone resorption, appears to be the major cause of the dental abnormalities which are less severe in the youngest (posterior) teeth. PMID- 2313607 TI - Quality of life in non-insulin-dependent diabetes and a comparison with insulin dependent diabetes. AB - The reported effects of diabetes on quality of life have been assessed in two groups of attenders at out-patient clinics: 1. One hundred and twenty-one non insulin-dependent diabetic patients randomly allocated to diet, tablet or ultralente insulin therapy; 2. Fifty-seven patients with insulin-dependent diabetes consecutively attending an out-patient clinic. The overall picture for those with non-insulin-dependent diabetes was of relatively little disruption to most areas of life, but 27% reported considerable loss of enjoyment and reduction in social life. High fasting plasma glucose was significantly associated with fatigue and leisure difficulties. The type of therapy, tablet, diet or insulin, made little difference to psychological, social or attitude variables. Those with insulin dependent diabetes showed similar psychological morbidity, but described a rather different pattern of social consequences with more effects on work and less on leisure. PMID- 2313608 TI - The Pain Cognitions Questionnaire. AB - This paper reports the development of the Pain Cognitions Questionnaire. This was administered to 90 mixed chronic pain patients and an exploratory factor analysis revealed two negative and two positive factors. Significant associations were observed between scores on the negative factors and measures of pain severity and mood. No clear relationship emerged, however, for positive cognitions and pain or mood variables. The implications of these findings for the assessment and treatment of chronic pain are discussed. PMID- 2313609 TI - Family history of hypertension and cardiovascular reactivity to forehead cold stimulation in black male children. AB - The effects of family history of hypertension on cardiovascular reactivity to forehead cold stimulation was examined in 16 black males from 11 to 14 years of age. Measures of blood pressure, heart rate, cardiac output, stroke volume and systemic vascular resistance were obtained during baseline, forehead cold stimulation and recovery phases. Diastolic blood pressure and systemic vascular resistance increases to the forehead cold stimulation were significantly greater in subjects with positive family histories of hypertension than in those with negative family histories. These findings are compared with the results of adult studies and discussed in terms of racial differences in alpha and beta adrenergically mediated cardiovascular reactivity. PMID- 2313610 TI - The evaluation of a cognitive behavioural treatment programme in outpatients with chronic pain. AB - This study is an attempt to investigate the efficacy of an outpatient cognitive behavioural group programme for the rehabilitation of patients with chronic pain. The programme, which took place over one afternoon per week for seven weeks and was conducted by a multidisciplinary team, aimed to increase patients' skills for coping with chronic pain and its social, emotional and physical consequences. Measures of pain intensity, mood, coping skills, physical disability and medication consumption were obtained on four separate occasions: twice pre treatment, immediately post-treatment and at one month follow-up. Repeated measures analysis of variance showed significant improvements in mood, coping skills, physical disability and analgesic consumption despite less clear-cut improvement in ratings of pain intensity. These results parallel the findings of similar studies in the U.S.A. and their implications for the provision of services to chronic pain patients in the U.K. is discussed. PMID- 2313611 TI - The relationship between heart rate and mood in real life. AB - Very little is known about the relationship between stress and cardiovascular responses in everyday settings. The three subjective states of Stress, Arousal and Time Pressure were measured every 30 min during a normal day in 32 healthy male volunteers and related to heart rate, which was measured continuously using standard ambulatory techniques. An index of the subjects physical activity was derived from the muscle activity of the thigh. Heart rate related to emotional state in very few subjects when time-series statistical methods, which take into account the autocorrelated nature of the data, were used. The relationship was further reduced when allowance was made for concurrent physical activity. The minority of subjects who exhibited a significant association between heart rate and mood variations were significantly more anxious, reported more anger, and had higher systolic blood pressures at rest than subjects who did not show a relationship between mood and heart rate. PMID- 2313612 TI - Premenstrual emotional changes a prospective study of symptomatology in normal women. AB - Fifty-one subjects completed a modified version of the Moos Menstrual Distress Questionnaire daily for 8 weeks. The true purpose of the study was not revealed. These prospective data showed no pattern of increase in symptoms of negative affect during the premenstrual or menstrual phases, although the majority of women retrospectively reported having experienced premenstrual tension during the study. Explanations for this discrepancy in terms of an information processing bias and the popularising of internal hormonal explanations are offered. A number of demographic and menstrually related variables are investigated and found to show no relationship to the experience of PMT in this sample. No evidence is found to suggest that older women are more likely to experience PMT. PMID- 2313613 TI - Cross-validation of the factor structure of the Toronto Alexithymia Scale. AB - The Toronto Alexithymia Scale (TAS) is a self-report measure of the alexithymia construct. In previous studies with college students, the TAS demonstrated excellent psychometric properties including a 4-factor structure theoretically congruent with the alexithymia construct. The present study attempted to cross validate the factor structure of the TAS with samples of normal adults, psychiatric outpatients and college students. Congruence coefficients comparing the similarity of the factor structures for these three samples indicated good congruence for all four factors. The results provide further support for the validity of both the TAS and the alexithymia construct. In addition, the results provide evidence of the applicability of the scale to normal adult and clinical samples. PMID- 2313614 TI - The relationship between situational stress and phantom limb pain: cross-lagged correlational data from six month pain logs. AB - This study reports the results of the first investigation into the relationship between situational stress and phantom limb pain. Twenty-seven male amputees recorded their pain and overall stress levels daily for 180 days using a 1-10 rating scale. Three possible relationships into the etiology and/or maintenance of phantom limb pain were examined using cross-lagged correlational techniques: an isomorphic relationship (same time increases in pain lead to same time increases in stress and vice versa), a consequence relationship (increases in pain precede increases in stress), and a precursor relationship (increases in stress precede increases in pain). Thirty-seven per cent of subjects demonstrated some significant precursor relationship. Although support was found for all three hypotheses, the most frequently observed relationship was the isomorphic one. Seventy-four per cent of subjects demonstrated some significant stress-pain relationship. The results lend support to the psychological theory underlying the use of psychophysiological interventions such as biofeedback and relaxation therapy in amputees with phantom limb pain. PMID- 2313615 TI - Measurement of psychiatric disorder in rheumatoid arthritis. AB - In a detailed physical and psychiatric assessment of 80 patients with definite or classical rheumatoid arthritis (RA) different instruments were used to measure psychiatric disorder. The prevalence of psychiatric disorder was 21% when assessed by the PSE/CATEGO programme and 24% according to RDC criteria, but these figures were nearly doubled if a lower threshold was used to define psychiatric disorder. This study demonstrates how symptoms directly attributable to arthritis may inflate the estimated prevalence of psychiatric disorder in RA and erroneously indicate a direct relationship between severity if RA and psychiatric disorder. In fact, the best prediction of psychiatric disorder resulted from using a combination of measures of social stress and severity of RA. PMID- 2313616 TI - Type A factors as predictors of somatic risk factors of coronary heart disease in young Finns--a six-year follow-up study. AB - Type A factors related to the level of somatic risk factors of coronary heart disease were studied in 1209 healthy young Finns. They were 12-, 15- and 18-year old adolescents who were clinically examined three times within a six-year follow up period. The risk and non-risk groups were constructed on the basis of their risk level over three testings, separately in each somatic risk variable. Type A behavior was evaluated during the six-year follow-up using the AFMS questionnaire. The results showed that of the Type A factors 'hard-driving' had the strongest association with the somatic risk level. 'Aggression competitiveness' was also related to the risk but not very strongly. 'Impatience' was of no importance while 'engagement-involvement' was likely to be a protective factor: a low score on it correlated with the risk. PMID- 2313617 TI - Experimental changes in pain threshold and severe pain threshold for electrically induced pain. AB - Pain and severe pain thresholds were measured in groups of 15 (Experiment 1) and 20 (Experiment 2) normal volunteers. In Experiment 1, the subjects underwent a series of ten constant level, painful stimuli each of 10 sec duration at an arbitrarily chosen level between the thresholds. This level was recorded. It ranged from 14% to 81% of the difference between thresholds. The thresholds were then remeasured. For the second experiment the experimental stimulus commenced at a non-painful level and increased over a period of 5 sec to a level midway between thresholds for a series of three stimuli and again thresholds were remeasured. An overall effect was demonstrable only in Experiment 2, where the severe pain threshold was significantly reduced (p less than 0.001). There was a marked individual variation with increases and decreases in both thresholds occurring in different individuals at significance levels varying from p less than 0.05 to p less than 0.001. No subject changed the two thresholds in opposite directions. Examination of the responses in Experiment 1 suggested that for any increase in either threshold to occur it was necessary that the repeated painful stimulus should be at a level below the mid-point between the two thresholds, but that this was not a sufficient condition. PMID- 2313618 TI - Coping with AIDS and HIV. PMID- 2313619 TI - Psychiatric nursing consultation: a different choice for nursing homes. PMID- 2313620 TI - Learning to laugh: humor as therapy. AB - Use of humor may indicate a person's mental health status, may reveal psychosocial problems and conflicts, and may indicate ability to cope with those problems and conflicts. Humor may also be one way of helping people more effectively cope with the stresses and strains of living in a complex world. Humor may be incorporated into psychotherapy, either as part of the therapist client relationship or as a humor program. The humor used by the author in a humor program with chronically mentally ill clients is the laughing with, not the laughing at, type. It deals with problems of life and of people living life. The stories, jokes, comic strips, and songs selected show how people perceive and laugh at the ironies and absurdities in their predicaments and are able to cope with, and frequently transcend, them. PMID- 2313621 TI - Ethical guidelines for confidentiality. Colorado Society of Clinical Specialists in Psychiatric Nursing. PMID- 2313622 TI - Reaching out to the chronically mentally ill homeless. PMID- 2313623 TI - [Physiopathology of nephrotoxicity of iodinated contrast media. New concepts]. PMID- 2313624 TI - [X-ray computed tomographic aspects of mesenteric panniculitis]. AB - Mesenteric panniculitis also known as lipodystrophy is an inflammatory condition of adipose tissue. A case of a 55 year old, female who presented a weight loss and a tender palpable mass located in the left flank is reported. CT patterns were not specific but might suggest the diagnosis: fatty mass, with a higher density than subcutaneous fat, located in the root of the mesentery and surrounding mesenteric vessels without distoting them. Intestinal loops were only pulled in periphery. This signs are not always present and even in this typical pattern mesenteric panniculitis could not be differentiated from liposarcoma. Thus an histological proof was needed. The evolution was good, with resolution of the abdominal pain. The knowledge of this rare Radioclinical syndrome should prevent any aggressive therapy. PMID- 2313625 TI - [Rectal stenosis. A rare complication of chronic salpingitis caused by an intrauterine device]. AB - The authors describe one case of rectal stenosis complicating chronic salpingitis in a patient carrying an intrauterine device. This observation is peculiar in that the inflammatory fibrous reaction is very intense, spreading all over the pelvis and forming a pseudotumoral mass sheathing the rectum. The clinical signs were mainly digestive, including a rectal syndrome: cramplike pelvic pain before defecation, tenesmus, constipation, abdominal pain and induration of the anterior aspect of the rectum observed during the clinical examination. Radiological examinations (barium enema, ultrasound, CT) show a tissue mass within the pelvis, with considerable thickening of the rectal wall. Ultrasound-guided biopsy in the pelvis yielded only nonspecific inflammatory signs with dominant fibrosis. The diagnosis of rectal stenosis caused by chronic salpingitis complicating the presence of an IUD was made only during surgery. PMID- 2313626 TI - [Dosimetry with thermoluminescence during mammography]. AB - A dosimetry study using lithium fluoride TL dosimeters was carried out during mammography in 34 patients in order to evaluate in vivo the dose of mammography rays received by these patients. The measures are made for one breast only, using two views: cranio-caudal and medio-lateral views with compression. The results show that skin entrance doses are going from 0.20 to 1.67 cGy in cranio-caudal view and from 0.15 to 1.75 cGy in medio-lateral view. The skin exit doses are from 0.001 to 0.21 cGy in cranio-caudal view and from 0.001 to 0.13 cGy in medio lateral view. The midplane doses estimated from the skin entrance dose and the graph of the deep yield are from 0.07 to 0.48 cGy. These doses are comparable with those founded by other authors, and though maximum, they stay very low. This is important for detect the breast cancer in order to reduce radiation risks. PMID- 2313627 TI - [High-field magnetic resonance imaging of the liver compared to x-ray computed tomography. Preliminary study apropos of 39 cases]. AB - Thirty nine patients with one or more focal hepatic lesions were examined by contrast enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI). A variety of pulse sequences--spin echo (SE), gradient echo (GE) and inversion recovery (IR)--have been reported in the literature on MRI concerning the detection and characterization of liver tumors. Multiple studies have compared MRI at different field strengths to CT. As controversy still exists concerning the optimal pulse sequence on MRI, CE-CT has been compared to T2 weighted SE sequence in this study. CT, as well as MRI, identified abnormalities in liver parenchyma in all patients. As far as detection of hepatic lesions is concerned, MRI and CE-CT were equal in 35 cases and MRI was superior in the other four cases. However, CT remains the examination of choice for detection of focal lesions, due to the short examination time, the low cost and the superiority in detection of extrahepatic pathology. PMID- 2313628 TI - Blastocyst formation by pig embryos resulting from in-vitro fertilization of oocytes matured in vitro. AB - Follicular oocytes collected from prepubertal gilts at a local slaughter house were matured (36 h), fertilized and developed in vitro. Of 785 embryos, 190 (24%) embryos cleaved to the 2-4 cell stages with blastomeres of regular size by 33 h after insemination. These cleaved embryos were surgically transferred into the oviducts of 4 synchronized recipient gilts and recovered from the uterine horns 4 or 7 days later: 13 morulae, 2 blastocysts and 1 expanded blastocyst were recovered after 4 days and 3 hatched blastocysts were recovered 7 days after transfer. Re-culture in vitro sustained further development of morulae recovered 4 days after transfer: 11 of 13 morulae had developed to the blastocyst/hatched blastocyst stages. Overall, 17 of 190 (9%) embryos developed to the blastocyst stage. The results indicate that pig oocytes can be matured and fertilized in vitro, and subsequently develop to the blastocyst stage. PMID- 2313629 TI - Failure of platelet-activating factor (PAF-acether) to induce decidualization in mice and failure of antagonists of PAF to inhibit implantation. AB - The possible role of platelet-activating factor (PAF) in the uterine responses associated with implantation was investigated. Attempts to trigger a decidual cell response in the uteri of hormonally sensitized, ovariectomized mice by instilling PAF-acether (1-1000 ng) intraluminally were unsuccessful. The effect of PAF antagonists on implantation was investigated in females ovariectomized on Day 3 of pregnancy and treated with progesterone. Implantation was induced in these females by injection of 10 ng oestradiol-17 beta on Day 8. Hourly intraperitoneal injections of three PAF antagonists (WEB 2086, CV 3988 and BN 52021 at doses of 1.2-1.4 mg/kg) given over a 24-h period starting 1 h before the injection of oestradiol-17 beta had no significant effect on the occurrence of implantation sites. Intraluminal injection of WEB 2086 (15 micrograms) or BN 52021 (5 micrograms) either 3 h before or 6 h after the nidatory oestradiol also had no significant inhibitory effect on implantation. SRI 63-441 given once daily over the first 4 days of pregnancy at a dose of 40 micrograms/30 g body weight had no inhibitory effect on the establishment of pregnancy. These results are not consistent with a critical role for PAF in implantation in mice. PMID- 2313631 TI - Urinary androgen concentrations and social status in two species of free ranging zebra (Equus burchelli and E. grevyi). AB - In both species of zebra, breeding males had higher urinary androgen concentrations (ng androgens/mg Cr) than did non-breeding bachelor males (30.0 +/ 5.0 (N = 9) versus 11.4 +/- 2.8, (N = 7) in the plains zebra; 19.0 +/- 2.2 (N = 17) versus 10.7 +/- 1.2 (N = 14) in the Grevy's zebra). In the more stable family structure of the plains zebra (single male non-territorial groups) variations in androgen concentrations could not be ascribed to any measured variable. In the Grevy's zebra, androgen values were significantly lower in samples taken from territorial (breeding) males which had temporarily abandoned their territories (N = 4) and the urinary androgen concentration for a male on his territory was negatively correlated with the time since females last visited the territory. PMID- 2313630 TI - Biochemical composition of washed human seminal coagulum in comparison to sperm free semen from the same donors. AB - Intra-individual inter-ejaculate variations in the amounts of protein, fructose, N-acetylamino sugar, phosphate, sialic acid and amino sugar in washed coagulum from normal ejaculates of men were highly consistent (N = 9). All the prostatic components studied (acid phosphatase, zinc, calcium and citric acid), except zinc, in the washed coagulum were reduced by 90% of their values in semen (N = 5). The seminal vesicular markers (fructose, N-acetylamino sugar and phosphate) had no association with the coagulum structure and represented the soluble components (N = 5). The concentrations of protein and zinc in the coagulum were higher than those of semen by 114% and 32% respectively. The coagulum contained sialic acid and amino sugar as integrated components. PMID- 2313632 TI - Embryo implantation associated with increase in T-cell suppressor factor in the uterus and spleen of mice. AB - The concentrations of T-cell suppressor factor (TsF) were examined by competitive binding assays in the uterus, spleen, and regional lymph nodes draining the uterus in Day-5 pregnant mice or in ovariectomized mice given hormone treatments to induce conditions of delayed implantation or implantation. The amounts of immunoreactive TsF on Day 5 of pregnancy were 2.055 +/- 0.302, 0.803 +/- 0.088, 0.426 +/- 0.136 ng TsF/mg extractable protein for the regional lymph nodes, spleen and uterus, respectively, during Day 5 of pregnancy. When implantation was prevented by ovariectomy on Day 4 followed by treatment with only progesterone, amounts of TsF (as a % of Day 5 value) were decreased to 57% in the uterus and increased to 141% in the spleen and 180% in the regional lymph nodes. When implantation was then initiated with the addition of oestradiol-17 beta to the progesterone treatment, amounts of TsF were increased to 206% in the uterus, 318% in the spleen, and remained unchanged at 180% in the regional lymph nodes. These experiments suggest that the amounts of TsF in the uterus and spleen are dependent upon the implantation process, whereas amounts of TsF in the regional lymph nodes are independent of this event. PMID- 2313633 TI - Decidualization in the post-partum uterus of the mouse. AB - Unilaterally ovariectomized mice were allowed to complete one pregnancy before the second ovary was removed and sensitivity to decidualization was induced by hormone administration. The virgin uterine horn and the post-partum horn were stimulated to decidualize by the intraluminal injection of arachis oil. A greater decidual response was found in post-partum horns than in virgin horns. The foci of decidual induction in post-partum horns were regularly spaced reflecting the regular spacing of used and unused areas of the uterus. A focus of decidual induction occurred in 68% of the recently used uterine areas observed, i.e. areas associated with post-partum nodules. When compared with foci of decidualization in adjacent unused areas of the uterus, none of the decidualized used zones showed more decidual tissue, about half showed less decidual tissue and half showed the same amount of decidual tissue. The remaining 32% of used zones were not associated with foci of decidual induction. The results indicate that decidualization can be induced in recently used zones of the uterus using a non traumatic method of induction, but that used zones are associated with less decidual tissue than unused zones of the post-partum uterus. PMID- 2313634 TI - Identification, immunoaffinity purification and partial characterization of a human decidua-associated protein. AB - A crude extract of pooled early-pregnancy decidual tissue was enriched for soluble decidual proteins by exhaustive affinity absorption with antibodies to human serum proteins immobilized on Eupergit C. The partly purified extract was used to prepare monoclonal antibodies. A monoclonal antibody was obtained recognizing an antigen present in extract of decidual tissue and not in extract of proliferative endometrium. The monoclonal antibody was used for immunoaffinity purification of the decidua-associated protein. By SDS-PAGE analysis, under reducing conditions it yielded 2 bands at apparent molecular weights of 55,000 and 25,000. Under non-reducing conditions a single protein band at apparent molecular weight of 200,000 was observed. The Mr 200,000 protein was named hDP200 and the Mr 55,000 protein was named hDP55. It is suggested that hDP55 is a subunit of the hDP200. The hDP200 did not react with polyclonal antibodies specific for PP12 and PP14. PP14 has been shown to be immunologically indistinguishable from PEP and alpha 2-PEG. Our data therefore suggest that hDP200 is a novel human decidua-associated protein. PMID- 2313635 TI - Copulatory behaviour and coagulum formation in the female reproductive tract of the Australian hopping mouse, Notomys alexis. AB - Hopping mice were examined to study two interrelated questions: (1) when groups of adults of both sexes are kept together in one cage in the laboratory is there evidence that the females copulate with only one male, and (2) is a copulatory plug formed in the female tract after ejaculation? The findings indicate that a female will sometimes lock with more than one male in the group during an oestrous period induced by administration of exogenous gonadotrophins, and that a small 'plug' of soft material forms post coitum in the more caudal parts of the female tract. Individuals of this species, therefore, do not appear to be strictly monogamous, at least in this artificial laboratory situation. Although a coagulum is formed, this is quite different from the typical hard copulatory plug that occurs in common laboratory murids; it may possibly reduce sperm backflow from the lower region of the female reproductive tract. PMID- 2313636 TI - Onset of secretion of proteins with antiviral activity by pig conceptuses. AB - In Exp. 1, antiviral activity was detected in Day-15 pregnant uterine flushings (6222 +/- 2167 units/ml) and in conceptus culture medium collected at 0, 1, 2, 4, 8, 16, 24, 32, 40, and 48 h (95, 375, 650, 1216, 1600, 2100, 2017, 2083, 3500 and 5000 units/ml, respectively; R2 = 0.81, P less than 0.01; y = 190.0 + 252.7x - 11.2x2 + 0.2x3. In Exp. 2, antiviral activity of Day-15 conceptus culture medium was reduced 99% after boiling for 20 min (P less than 0.01) and, after 18 h dialysis (6000-8000 Mr cut-off), 100% of the activity was in the retentate. In Exp. 3, antiviral activity was not detected in cultures of conceptuses from Days 10 and 11 and activity was maximal for Day 14 and Day 15 conceptuses (2100 and 2083 units/ml, respectively). Effects of day were best described by a quadratic regression equation (y = 17,652 - 3263x + 150x2; R2 = 0.55, P less than 0.01). In Exp. 4, changes in antiviral activity detected in uterine flushings from pregnant gilts on Days 8, 10, 11, 12, 14 and 15 (1.3, 0, 6.7, 63.3, 580 and 1663 units/ml, respectively) were described by the equation y = -20,743 + 6189x - 606x2 + 20x3 (R2 = 0.85, P less than 0.01). In Exp. 5, low antiviral activities (5-30 units/ml) were detected in all plasma samples collected from the uterine artery and uterine vein of pregnant and cyclic gilts, but values were not significantly influenced by pregnancy status, day or site of collection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313637 TI - Influence of the endometrium, protease inhibitors and freezing on antiviral activity of proteins secreted by pig conceptuses. AB - In Exp. 1, only medium from cultures containing conceptus tissue had antiviral activity (P less than 0.05). Addition of Day-15 pregnant endometrium or Day-14 cyclic uterine flush proteins to cultures containing 200 mg conceptus tissue decreased antiviral activity (conceptus x endometrial protein interaction, P less than 0.06). Effects of endometrium (-54%) and uterine flush proteins (-40%) on antiviral activity of conceptus cultures did not differ from each other (P greater than 0.10). In Exp. 2, antiviral activity was only detected in cultures containing conceptus tissue (P less than 0.06). The amount of antiviral activity in cultures of Day-15 conceptus tissue was not influenced differently (P greater than 0.10) by culture in medium conditioned by endometrium from Day 10 or Day 12 of pregnancy. However, antiviral activity was undetectable in medium conditioned by endometrium from one of the Day-12 gilts. In Exp. 3, antiviral activity was present in medium from only 1 of 3 cultures from Day-12 gilts when assayed unfrozen. Antiviral activity was lower (P less than 0.01) in cultures of conceptuses from Day 12 than Day 14 of pregnancy; however, antiviral activity increased quadratically (P less than 0.05) when cultures contained 0, 0.01, 0.1 and 1.0 units/ml aprotinin, respectively. Freezing and thawing culture medium did not reduce (P greater than 0.10) antiviral activity compared to medium assayed unfrozen (1438 vs 1354 units/ml, respectively). These results suggest a regulatory influence of the endometrium on secretion of antiviral proteins by pig conceptuses in vitro. PMID- 2313638 TI - Expression of cellCAM-105 in the apical surface of rat uterine epithelium is controlled by ovarian steroid hormones. AB - Affinity-purified antibodies to cellCAM-105, an adhesive cell surface glycoprotein, were used in immunohistochemical investigations of rat uteri at various functional stages: (i) the oestrous, pro-oestrous, metoestrous, and dioestrous stages of the oestrous cycle, (ii) Days 1-8 of normal pregnancy, (iii) delayed implantation, (iv) 18 h after oestrogen reactivation from delay of implantation, and (v) juvenile rats, and normal ovariectomized adults, respectively, before and after experimental injection of progesterone and/or oestrogen. CellCAM-105 was present in the apical zones of the luminal and glandular epithelium cells in a stage-specific and hormone-dependent manner. The results indicate that: (1) steroid hormones are essential for the expression of cellCAM-105 in the uterine epithelial cells; (2) progesterone induces cellCAM-105 expression in the glandular epithelium, and oestrogen induces cellCAM-105 expression in the luminal epithelium; (3) progesterone induces down-regulation of cellCAM-105 from the surface of the uterine luminal epithelium of juvenile rats; (4) cellCAM-105 is absent in the luminal epithelial cells but present in the glandular epithelial cells of the rat uterus at the time of blastocyst implantation. PMID- 2313639 TI - Secretion of prostaglandins and progesterone by cells from corpora lutea of mares. AB - Corpora lutea (CL) were collected from mares during early (Day 4-5), mid- (Day 8 9), and late (Day 12-13) dioestrus. Dispersed cell suspensions were obtained by enzymic digestion of tissue. Two distinct luteal cell populations (large and small) were observed. The proportion of small luteal cells significantly increased as age of CL advanced. Cells (2 x 10(6)) from CL which were incubated for 24 h secreted prostaglandin (PG) F, PGE-2 and 6-keto-PGF-1 alpha (the stable metabolite of prostacyclin). Higher concentrations of all PGs were produced by cells from CL at early dioestrus than from those at mid- or late dioestrus. The ratio of PGF:PGE-2 increased from 0.33 in CL of early dioestrus to 1.34 in CL of mid-dioestrus, whereas ratios of PGF:6-keto-PGF-1 alpha remained relatively constant (approximately 0.6). The ratio of PGE-2:6-keto-PGF-1 alpha from CL decreased between early (3.27) and mid-dioestrus (0.43). Addition of LH, dbcAMP, or ionophore to cell cultures did not consistently affect secretion of progesterone or PGs by luteal cells. It is suggested that prostaglandins produced by luteal cells of mares may contribute to control of luteal function and that the changing ratios of prostaglandins may be more important in controlling the lifespan of the CL than absolute concentrations of each. PMID- 2313640 TI - Evaluation of the pregnancy immunotrophism hypothesis by assessment of the reproductive performance of young adult mice of genotype scid/scid.bg/bg. AB - The hypothesis that enhancement of pregnancy success results from immune recognition of the conceptus was evaluated by studying reproductive performance in a new line of mice deficient in NK cells and lacking B cells and T cells. Doubly mutant mice of genotype scid/scid.bg/bg are both viable and fertile. The numbers of offspring born to pairs of this genotype were not different from numbers born to heterozygous pairs. Differences in prenatal loss could not be found between genotypes by counts of either fetal resorption sites or corpora lutea. The timing of developmental stages and the differentiation of trophoblast, placenta, decidua and metrial gland in scid/scid.bg/bg mice appeared normal. These results suggest either that lymphokine influences on trophoblast cells in vivo do not contribute, in a major way, to pregnancy success or that the important cytokines are derived from uterine cell populations that are not classical, mature B cells, T cells or NK cells. PMID- 2313641 TI - Oocyte recovery, maturation and fertilization in vitro in the puma (Felis concolor). AB - Eight female pumas were treated i.m. with 1000 (N = 5) or 2000 (N = 3) i.u. PMSG followed 84 h later by 800 i.u. hCG. Eggs were recovered 24-26 h after hCG from ovarian follicles by using laparoscopy and transabdominal aspiration. Mature eggs were inseminated in vitro 4-6 h later whereas immature eggs were cultured for 24 h and then inseminated. Electroejaculates from 3 pumas were diluted with mKRB before insemination to evaluate the influence of sperm concentration on fertilization. Seven of 8 pumas responded with follicle development, and 140 eggs were recovered from 145 follicles (96.6%; 77 mature, 43 immature, 20 degenerate eggs; mean +/- s.e.m., 20.0 +/- 5.9 eggs/female). Overall fertilization rate was 43.5% (total eggs fertilized = 40) despite using inseminates containing 82-99% pleiomorphic spermatozoa. Of the 36 immature oocytes matured in vitro and inseminated, 12 were fertilized even though 50% of the inseminating spermatozoa contained an acrosomal defect. Fertilization rate of mature oocytes collected from follicles appeared unrelated (P greater than 0.05) to PMSG dose or number of spermatozoa/inseminate. This study demonstrates that a high proportion of follicular eggs can be recovered laparoscopically from adult pumas treated with PMSG and hCG. These gametes are capable of being fertilized in vitro (immediately or after maturation in vitro) even with low quality semen with a high incidence of sperm pleiomorphisms. PMID- 2313642 TI - Effect of glutathione depletion on the cytotoxicity of xenobiotics and induction of single-strand DNA breaks by ionizing radiation in isolated hamster round spermatids. AB - The role of glutathione (GSH) in cellular protection mechanisms in round spermatids from hamsters was studied. Isolated spermatids were largely depleted of GSH by treating the cells for 2 h with the GSH conjugating agent diethyl maleate (DEM). This treatment resulted in a 90% decrease of the cellular GSH content, but did not affect the ATP content. Exposure of isolated spermatids to cumene hydroperoxide (CHP), a compound which is detoxicated by the GSH redox cycle, showed that the cytotoxicity of the peroxide was markedly potentiated by GSH depletion of the cells. The cytotoxicity was reflected by the cellular ATP content. A decrease of the ATP content of the GSH-depleted spermatids was observed at 5-6-fold lower CHP concentrations, as compared to control cells. An increased cytotoxicity in GSH-depleted cells was also observed using 1-chloro-2,4 dinitrobenzene (CDNB), which is a reactive compound that is detoxicated by glutathione conjugation. The induction of single-strand DNA breaks by gamma radiation was 3-5-fold higher in GSH-depleted spermatids as compared to control cells. This radiation-induced damage was estimated under hypoxic conditions (500 p.p.m. O2 in N2). GSH depletion did not affect the repair of single-strand DNA breaks following the irradiation. The present results indicate that cellular GSH has an important function in the defence mechanisms of round spermatids against peroxides, electrophilic xenobiotics and radiation-induced DNA damage. PMID- 2313643 TI - Measurement of natural killer activity and target cell binding by mouse metrial gland cells isolated by enzymic or mechanical methods. AB - Cells of the metrial glands of mice were isolated by enzymic or mechanical dissociation procedures. Morphological observations indicated that up to half of the enzymically dissociated cells and nearly all of the mechanically dissociated cells were granulated metrial gland cells, but the presence of some fibroblast like stromal cells among the latter population was not ruled out. Moreover, the granulated metrial gland cells had lost a substantial part of their granule content during isolation. Both cell preparations had little or no natural killer (NK) activity, indicating either that granulated metrial gland cells are not NK like or that their NK activity was impaired by loss of granule-associated lytic substances or by other factors. Enzymically dissociated metrial gland cells did not bind significantly to the NK target cell YAC-1, nor did they develop granules, NK activity, or the ability to bind YAC-1 cells during culture in vitro, either in normal medium or with the addition of indomethacin or lymphokines. Mechanically dissociated metrial gland cells bound avidly to YAC-1 cells but not to P815 cells or adult thymus cells, which are not NK target cells. Since many if not most of the mechanically dissociated metrial gland cells appeared morphologically to be granulated metrial gland cells, their selective binding to an NK target cell suggests that granulated metrial gland cells may be related in some way to NK cells. PMID- 2313644 TI - Correlation of infertility with altered tubal morphology and function in mice with salpingitis induced by a human genital-tract isolate of Chlamydia trachomatis. AB - Progesterone-treated C3H mice were inoculated into the uterus or ovarian bursa with a human genital tract isolate of C. trachomatis (serovar E), or with control medium alone. The mice were then observed at various times up to 260 days after inoculation. Before being killed the mice were given pituitary gonadotrophins to induce ovulation. Eggs were sought in the oviducts and ciliary activity in the fimbrial and ampullary sections of the oviducts was determined by light microscopy, before detailed examination by scanning electron microscopy. Eggs were visible in all control oviducts and both mucosal ultrastructure and ciliary activity appeared normal. By contrast, eggs were not recovered from the inoculated oviducts of mice infected intrabursally, nor was ciliary activity observed up to 28 days after inoculation. After this, ciliary activity reappeared but eggs were still not transported to the oviduct. Ultrastructural studies suggested that severe mucus congestion accompanied by tubal oedema and loss of ciliated epithelia play a major role in the aetiology of chlamydial-induced tubal damage. Infertility following chlamydial salpingitis could be associated with failure of egg transportation to the oviduct. Egg transport was still impaired even when luminal ciliary activity, ultrastructural integrity and patency had recovered. Our results suggest that chlamydial salpingitis in this mouse model closely resembles the human disease in its pathology and consequences for fertility, making the model particularly relevant for research on chlamydial vaccine development. PMID- 2313645 TI - Cytoplasmic projections of trophectoderm distinguish implanting from preimplanting and implantation-delayed mouse blastocytes. AB - A scoring scheme was devised to characterize visually the morphological differentiation of whole-mount, unfixed mouse blastocysts. Embryos were recovered from groups of intact mice (implanting embryos) and mice ovariectomized on Day 3 of pregnancy (implantation-delayed embryos) every 3 h from 18:00 h on Day 4 until 12:00 h on Day 5. Blastocyst differentiation was assessed according to the presence of a zona pellucida, the appearance of the outer margin of trophectoderm cells, the visibility of the blastocoele and the relative size of the inner cell mass. The results obtained indicate that, during this period, implanting and implantation-delayed mouse blastocysts lose the zona as well as exhibit rounded trophectoderm cells, an enlarged inner cell mass and an increasing opacity of the blastocoele. In contrast, the trophectoderm cells of implanting blastocysts only exhibit extensive cytoplasmic projections, probably due to remodelling of the intracellular cytoskeleton. Growth of the inner cell mass appeared to precede the other morphological changes in the majority of blastocysts, and thus might be a prerequisite for further differentiation. The rate of blastocyst differentiation and the survival of embryos were adversely affected by the condition of delayed implantation, induced by ovariectomy. This study suggests that the appearance of cytoplasmic projections from trophectoderm cells is central to the control of blastocyst implantation. PMID- 2313646 TI - Stimulation of protein secretion in the initial segment of the rat epididymis by fluid from the ram rete testis. AB - Zone 1A of the ductus epididymidis was perfused with ovine rete testis fluid (nRTF) and modifications of it, and a synthetic medium (sRTF) based on the inorganic composition of nRTF. There was little fluid transport by the duct mucosa and nRTF stimulated protein secretion. The secretagogue activity was not extracted by charcoal, was sensitive to protease digestion and was present in a portion of nRTF with a molecular weight of greater than 10,000. The addition of bovine serum albumin to the sRTF stimulated protein secretion, but not to the same extent as equal amounts of protein in nRTF. Polyacrylamide gel electrophoresis of the perfusates showed that proteins with molecular weights of 19,000 (all rats studied), and 22,000, 30,000 and 60,000 (at least half the rats studied) were secreted into the perfusion fluids as well as some blood proteins, but the pattern of secretion was not affected by the composition of the perfusion fluid. PMID- 2313647 TI - Effects of prostaglandin and prolactin on luteolysis and parturient behaviour in the non-pregnant tammar, Macropus eugenii. AB - In Exp. 1 non-pregnant female tammars were injected, on Day 26 (the day parturition would normally occur) after removal of pouch young, with saline, 200 micrograms ovine prolactin or 5 mg PG and changes in plasma concentrations of progesterone, prolactin, PGF-2 alpha metabolite (PGFM), oestradiol-17 beta and LH were determined. Luteolysis occurred in females treated with prolactin alone, while treatment with PG first induced a rapid rise in prolactin and subsequently a significant decrease in plasma progesterone. After prolactin treatment the oestradiol peak, oestrus and the LH surge were advanced significantly compared to the saline-treated females. In Exp. 2 the effects of the same treatments as used in Exp. 1 were determined on Day 23 and again on Day 26 after removal of pouch young in non-pregnant females. On Day 23 both prolactin and PG induced significant elevations in plasma progesterone, but luteolysis did not occur. On Day 26 the treatments initially induced significant elevations in plasma progesterone but these were followed by luteolysis within 8-12 h after treatment. PG treatment induced parturient behaviour in the non-pregnant females within 3-21 min and this persisted during the period that plasma concentrations of PGFM were elevated. The results show that PG induces birth behaviour and the release of prolactin, while prolactin first induces an elevation of plasma progesterone concentrations and, in the mature CL on Day 26, subsequently induces luteolysis. PMID- 2313648 TI - Control of parturient behaviour by prostaglandin F-2 alpha in the tammar wallaby (Macropus eugenii). AB - Nulliparous female tammar wallabies during the non-breeding season and adult male wallabies were treated with PGF-2 alpha at doses of 0.008, 0.04, 0.2 and 1.0 mg/kg. All the male and female wallabies responded to the three highest doses by showing parturient behaviour. At the lowest dose 4/4 males and 1/4 females responded. The peak concentrations of PGF-2 alpha metabolite (PGFM) in the peripheral plasma after administration of 0.008, 0.04 and 0.2 mg PGF-2 alpha/kg were 0.70 +/- 0.08, 3.02 +/- 0.37 and 8.48 +/- 0.76 ng/ml (mean +/- s.e.m.). Since the peak plasma concentrations of PGFM at normal parturition are reported to be 2.5 +/- 0.9 ng/ml, parturient behaviour can be induced by physiological concentrations of exogenous PGF-2 alpha. The effectiveness of PGF-2 alpha in males indicates that parturient behaviour is probably a result of a direct action of PGF-2 alpha on the brain, rather than a response to uterine or vaginal contractions. These experiments confirm that PGF-2 alpha is an important behavioural hormone in the tammar wallaby. PMID- 2313649 TI - Concentrations of nutrients in mouse oviduct fluid and their effects on embryo development and metabolism in vitro. AB - An ultramicrofluorometric technique was used to analyse the nutrient composition of mouse oviduct fluid. The concentrations of pyruvate, glucose and lactate in the vicinity of the cumulus mass were 0.37, 3.40 and 4.79 mM respectively. In the absence of cumulus cells, the concentration of pyruvate was significantly reduced, to 0.14 mM, while the concentration of glucose was significantly increased to 5.19 mM. Glutamine, which may help to overcome the '2-cell block' in mouse embryos in culture, was present at a concentration of 0.20 mM. A modified medium (MTF) in which the concentration of nutrients was similar to that in mouse oviduct fluid was prepared and its effects on embryo development and metabolism in vitro were compared with that of a conventional embryo culture medium (M16). The percentage of zygotes forming blastocysts in vitro by Day 5 was similar in both media (82% in M16, 79% in MTF). Rates of development, as assessed by cell number, were also comparable. However, the proportion of glucose consumed which was converted to lactate increased dramatically following culture; from 44% in fresh blastocysts, to 73% and 91% in blastocysts derived from 8-cell embryos cultured for 24 h in media MTF and M16 respectively. PMID- 2313650 TI - A technique for quantifying the amount of macromolecule injected into cells of the early mouse embryo. AB - A simple technique for the quantification of the volume injected into an individual mouse egg or blastomere is described. The method does not seem to have deleterious effects on development, allows the progeny of the injected cell to be identified and permits the measurement of the injected volume to be made up to 48 h after the time of injection. PMID- 2313651 TI - Steroid synthesis in ovarian homogenates from immature mice treated with diethylstilboestrol in neonatal life. AB - Female mice of the NMRI strain were treated with the synthetic oestrogen diethylstilboestrol (DES) for the first 5 days after birth. Pools of ovaries were removed from groups of 6-, 12-, 21-, 28- and 56-day-old females. An homogenate of an ovarian pool was incubated for 1 h in the presence of [3H]pregnenolone. Synthesized steroids were extracted and separated in a two-dimensional thin-layer chromatography system. Homogeneity of tentative steroids was verified with recrystallization to constant specific activity. Synthesis of [3H]progesterone and [3H]testosterone was demonstrated at 6 days, [3H]androstenedione at 12 days, [3H]17 alpha-hydroxyprogesterone at 21 days, and [3H]oestradiol-17 beta at 28 days. Up to 28 days (21 days for progesterone), the synthetic activity was lower in homogenates of DES-exposed ovaries than in control homogenates. After 28 days, values for recovered [3H]progesterone, [3H]androstenedione and [3H]oestradiol-17 beta were higher in DES homogenates than in control homogenates while the reverse was true for [3H]17 alpha-hydroxyprogesterone and [3H]testosterone. The results are compatible with an early and direct DES inhibitory effect on ovarian steroidogenesis and, later in immature life, a DES-induced disruption of the normal FSH-LH stimulation of ovarian development. PMID- 2313652 TI - Genetic identification of non-specific esterases of the mouse cauda epididymidis and description of esterase-28, a new carboxylesterase isoenzyme (EC 3.1.1.1). AB - Twenty-five (25) electrophoretic bands with esterase activity were distinguished in supernatants of cauda epididymidis of DBA/2J mice. Twenty (20) of these were assigned to 10 genetically defined esterases (ES-1, ES-2, ES-3, ES-6, ES-7, ES 11, ES-14, ES-17, ES-19, ES-22) which were already known from investigations of other mouse tissues. Furthermore, ES-10 was identified in cauda supernatants after isoelectric focussing. A hitherto genetically undefined esterase was assigned to locus Es-28 which was expressed solely in the epididymis. Three phenotypes were distinguished: ES-28A was present in the majority of the inbred strains examined. ES-28B was observed in AKR/Han mice and ES-28C was found in SEG/1 mice. PMID- 2313653 TI - Enrichment of the stages of the seminiferous epithelium in vitamin A-replaced vitamin A-deficient rats. AB - Morphometric study revealed that, at 40 days after the start of vitamin A replacement, A1 spermatogonia and preleptotene spermatocytes appeared in more than 70% of the whole mounts of seminiferous tubules of vitamin A-deficient rats. By 42 days, the appearance of these cell types was reduced by 50%, and A2 and A3 spermatogonia were predominant. By 46 days, A1-A3 spermatogonia appeared in less than 30% of the tubular length while A4, intermediate and B spermatogonia became the major cell types in the basement compartment of seminiferous tubules. The predominance of spermatogonia noted at given times was corroborated by higher frequencies of tubular cross-sections of stages in which that particular type of spermatogonium resides. These results indicate that seminiferous tubules of vitamin A-replaced-vitamin A-deficient rats are 'enriched' for particular stages. Tracing the development of [3H]thymidine-labelled preleptotene spermatocytes revealed normal kinetics of germ cell differentiation in these animals. Furthermore, the spermatogonial proliferations in the vitamin A-replaced-vitamin A-deficient rats were quantitatively normal. We suggest that vitamin A replacement may result in temporal suppression of the differentiation of A2-B spermatogonia, leading to a stimulation or synchronization of certain groups of undifferentiating spermatogonia which undergo active proliferation simultaneously. These synchronized populations of spermatogonia continue to proliferate and differentiate, thus resulting in the stage-enrichments noted at later times. PMID- 2313654 TI - Effects of luteinizing hormone on luteal cell populations in hypophysectomized ewes. AB - To examine the effect of purified LH on development and function of luteal cells, 27 ewes were assigned to: (1) hypophysectomy plus 2 micrograms ovine LH given i.v. at 4-h intervals from Days 5 to 12 of the oestrous cycle (oestrus = Day 0; Group H + LH; N = 7); (2) hypophysectomy with no LH replacement (Group N-LH; N = 6); (3) control (no hypophysectomy) plus LH replacement as in Group H + LH (Group S + LH; N = 7); (4) control with no LH treatment (Group S-LH; N = 7). Blood samples were collected at 4-h intervals throughout the experiment to monitor circulating concentrations of LH, cortisol and progesterone. On Day 12 of the oestrous cycle corpora lutea were collected and luteal progesterone concentrations, unoccupied receptors for LH and number and sizes of steroidogenic and non-steroidogenic luteal cell types were determined. Corpora lutea from ewes in Group H-LH were significantly smaller (P less than 0.05), had lower concentrations of progesterone, fewer LH receptors, fewer small luteal cells and fewer non-steroidogenic cells than did corpora lutea from ewes in Group S-LH. The number of large luteal cells was unaffected by hypophysectomy, but the sizes of large luteal cells, small luteal cells and fibroblasts were reduced. LH replacement in hypophysectomized ewes maintained luteal weight and the numbers of small steroidogenic and non-steroidogenic luteal cells at levels intermediate between those observed in ewes in Groups L-LH and S-LH. In Group H + LH ewes, luteal and serum concentrations of progesterone, numbers of luteal receptors for LH, and the sizes of all types of luteal cells were maintained. Numbers of small steroidogenic and non-steroidogenic cells were also increased by LH in hypophysectomized ewes. In Exp. II, 14 ewes were assigned to: (1) sham hypophysectomy with no LH replacement therapy (Group S-LH; N = 5); (2) sham hypophysectomy with 40 micrograms ovine LH given i.v. at 4-h intervals from Day 5 to Day 12 of the oestrous cycle (Group S + LH; N = 5); and (3) hypophysectomy plus LH replacement therapy (Group H + LH; N = 4). Experimental procedures were similar to those described for Exp. I. Treatment of hypophysectomized ewes with a larger dose of LH maintained luteal weight, serum and luteal progesterone concentrations and the numbers of steroidogenic and non-steroidogenic luteal cells at control levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2313656 TI - Effects of breeding season and mating on total number and distribution of spermatozoa in the epididymis of the brown marsupial mouse, Antechinus stuartii. AB - Changes in the number and distribution of spermatozoa in the epididymis of the adult brown marsupial mouse were examined during July/August in mated and unmated males. The effects of mating on epididymal sperm populations were studied in 2 groups of males each mated 3 times and compared with the number and distribution of spermatozoa in the epididymides of 4 unmated control groups. One testis and epididymis were removed from each animal (hemicastration) either before or early in the mating season to provide information on initial sperm content and distribution. The contralateral side was removed later in the mating season to examine the effects of mating or sexual abstinence on epididymal sperm distribution. Epididymal sperm number peaked in both the distal caput and distal corpus/proximal cauda epididymidis in late July. The total number of spermatozoa, including those remaining in the testis, available to each male at the beginning of the mating season in early August was approximately 4.4 x 10(6)/side. Although recruitment of spermatozoa into the epididymis from the testis continued until mid-August, sperm content of the epididymis reached a peak of about 3.5 x 10(6)/epididymis in early August. At this time approximately 0.9 x 10(6) spermatozoa remained in the testis which had ceased spermatogenic activity. Throughout the mating season, epididymal spermatozoa were concentrated in the distal corpus/proximal cauda regions of the epididymis and were replenished by spermatozoa from upper regions of the duct. Relatively few spermatozoa were found in the distal cauda epididymidis, confirming a low sperm storage capacity in this region. A constant loss of spermatozoa from the epididymis, probably via spermatorrhoea, occurred throughout the mating season and very few spermatozoa remained in unmated males in late August before the annual male die-off. Mating studies showed that an average of 0.23 x 10(6) spermatozoa/epididymis were delivered per mating in this species, but the number of spermatozoa released at each ejaculation may be as few as 0.04 x 10(6)/epididymis when sperm loss via spermatorrhoea is taken into account. We suggest that the unusual structure of the cauda epididymidis, which has a very restricted sperm storage capacity, may function to limit the numbers of spermatozoa available at each ejaculation and thus conserve the dwindling epididymal sperm reserves in order to maximize the number of successful matings which are possible during the mating season. PMID- 2313655 TI - Glycosphingolipids of human myometrium and endometrium and their changes during the menstrual cycle, pregnancy and ageing. AB - The glycolipid composition of human myometrium and endometrium was examined at various stages of maturation and reproduction. The major neutral glycolipids of both myometrium and endometrium were identified by high-performance thin-layer chromatography as globo-series glycolipids, Gb3 and Gb4. The major acidic glycolipids (gangliosides) were identified similarly as GM3 and GD3, with lesser amounts of GM1, GD1a, and GT1b. During pregnancy, GD3 expression declined in both myometrium and endometrium, whereas GM3 expression increased. Reciprocal changes in GM3/GD3 expression were mirrored by appropriate changes in the glycosyltransferases required for their synthesis; alpha 2----3sialyltransferase activity increased approximately 3-fold during pregnancy, while alpha 2--- 8sialyltransferase activity declined to about 20%. The results focus attention on the glycolipids of uterine tissues, their regulation, and their possible role in reproduction and fertility. PMID- 2313657 TI - Immunohistochemical localization of chorionic gonadotrophin on baboon placenta, dispersed trophoblast cells and those derived from blastocysts grown in vitro. AB - An immunohistochemical technique using a high specificity antiserum against baboon CG was used to demonstrate the presence of a CG-like material on: (1) fixed baboon placental sections collected between 31 and 39 days of gestation, (2) trophoblast monolayers derived from hatched embryos grown in vitro for 15 days and (3) trophoblast cells derived from cells dispersed from placentae collected between Days 31 and 39 of pregnancy. A specific radioimmunoassay was used to detect concentrations of baboon CG in daily spent medium. Immunohistochemical studies showed that material cross-reacting with CG was present on all the three sources of trophoblast. The embryos secreted CG from attachment onwards and immunoactive CG was measurable in daily spent medium collected from placenta-derived trophoblast cultures. It is concluded that baboon CG is localized in the syncytiotrophoblast of fixed placental sections and cellular trophoblast derived from cultured embryos and placental cells. PMID- 2313658 TI - Termination of pregnancy and induction of premature luteolysis by the antiprogestagen, mifepristone, in dogs. AB - Five pregnant beagle bitches were treated with 2.5 mg mifepristone/kg body weight, twice a day, for 4.5 days starting at Day 32 of gestation. Results of fetal ultrasonography and assay of serum progesterone concentrations every 2-4 days were compared to those in 5 control bitches. Mifepristone resulted in a premature (P less than 0.01) termination of pregnancy (36 +/- 1 vs 65 +/- 1 days), without side effects. The antiprogestagen also caused progesterone to decline to less than 1 ng/ml by Day 40-45 after the preovulatory LH peak (vs 64 67 days in controls) and reduced (P less than 0.05) mean concentrations on Days 34-50 (2.2 +/- 0.5 vs 6.3 +/- 0.3 ng/ml). The results suggest that antiprogestagen therapy is a safe means to terminate unwanted pregnancy in dogs, and that luteal function in pregnant bitches is dependent on luteotrophic support that is blocked by antiprogestagen treatment, directly or indirectly, due to termination of pregnancy. PMID- 2313659 TI - Dendritic cells and high endothelial venules in the rheumatoid synovial membrane. AB - Since dendritic cells are believed to play a crucial role in the pathogenesis of rheumatoid arthritis (RA) we studied the microenvironmental relationship of these cells with endothelial cells, lymphocytes and macrophages in the rheumatoid synovial membrane. With the monoclonal antibodies OKIa (MHC Class II determinants), RFD1 and L25 (both specific for "active" human dendritic cells) we identified large numbers of dendritic cells. With the monoclonal antibody HECA 452 [specific for a putative adhesion molecule notably present on high endothelial venules (HEV)], a subset of dendritic cells could be detected. HECA 452 positive dendritic cells were found in 2 basic patterns: (1) associated with small lymphoid cell clusters in the neighborhood of vessels with flat, HECA-452 negative endothelium, (2) at the periphery of dense organoid lymphoid infiltrates, surrounding HECA-452 positive HEV-like vessels. Our data suggest that the influx of HECA-452, L25, RFD1 and MHC Class II positive dendritic cells is an early event in the development of the inflammatory infiltrate found in the rheumatoid synovial membrane. The formation of organoid lymphoplasmacellular infiltrates with high endothelial venules would be secondary to this event. PMID- 2313660 TI - Intestinal permeability in ankylosing spondylitis. PMID- 2313662 TI - Impotence in systemic lupus erythematosus. PMID- 2313661 TI - Addison's disease in "primary" antiphospholipid syndrome. PMID- 2313663 TI - More on aseptic necrosis and glucocorticoids in systemic lupus erythematosus. PMID- 2313664 TI - Erythromelalgia in a patient with systemic lupus erythematosus treated with clonazepam. PMID- 2313665 TI - Legionnaires' disease and rheumatoid arthritis. PMID- 2313667 TI - Rheumatoid vasculitis with worsening nodulosis. PMID- 2313666 TI - Restrictive ventilatory defect associated with pulmonary hypertension in mixed connective tissue disease. PMID- 2313668 TI - Adrenal secretion of cortisol in patients with rheumatoid arthritis. AB - We studied secretory activity of the adrenal gland by determining cortisol blood levels throughout a 24-h cycle at 2-h intervals in 26 patients with rheumatoid arthritis (RA), not previously treated with glucocorticosteroids or disease modifying drugs. In patients with low erythrocyte sedimentation rates [(ESR) up to 40 mm/h] and medium disease activity (ESR between 40 and 80 mm/h), cortisol maxima and minima shifted to earlier times of the day whereas in patients with high activity (ESR higher than 80 mm/h) the circadian rhythm was lost or markedly reduced. The inflammatory activity of the RA significantly correlated with the adrenal cortisol secretion (linear regression analysis between ESR and the arithmetic mean value of cortisol throughout a 24-h cycle with a coefficient of regression r = 0.63, n = 26, p less than 0.001). The influence of mediators of inflammation, such as interleukin 1, on hypothalamic centers, stimulating the hypothalamus-pituitary-adrenal axis, is discussed. PMID- 2313669 TI - Cortisol catabolism by lymphocytes of patients with systemic lupus erythematosus and rheumatoid arthritis. AB - We have shown that low cortisol catabolism by lymphocytes correlates with a high sensitivity of the cells to the steroid. In the present study, we aimed to assess whether high resistance to corticosteroid treatment correlates with a high rate of cortisol catabolism by lymphocytes. Since patients with systemic lupus erythematosus (SLE) usually require high doses of corticosteroids, while patients with rheumatoid arthritis (RA) respond to relatively low doses of steroids, we compared the capability of lymphocytes of patients with SLE and RA to catabolize cortisol. The rate of cortisol catabolism obtained with the RA group was not significantly different from that obtained with the control group. The catabolism of cortisol by lymphocytes of the SLE group was significantly higher than both the control group (p less than 0.05) and the RA group (p less than 0.01). A significant correlation was demonstrated between the SLE disease activity index and rates of cortisol catabolism attained by lymphocytes of SLE patients (p less than 0.001). PMID- 2313670 TI - Transverse myelitis: a manifestation of systemic lupus erythematosus strongly associated with antiphospholipid antibodies. AB - All 4 patients with transverse myelitis (TM) included in a prospective study of 500 patients with systemic lupus erythematosus (SLE) tested for anticardiolipin (aCL) antibodies were found to be positive. To determine if the apparently strong association between transverse myelitis and antiphospholipid antibodies (aPLA) in patients with SLE continued to hold, we chose 12 patients with SLE with transverse myelitis from 2 institutions. Eleven of the 12 patients with SLE were tested for aCL and all but one was positive. Most of them (n = 8) had both IgG and IgM isotype aCL. The one who was negative had had a positive VDRL and prolonged APTT 15 months earlier, coinciding with the episode of transverse myelitis. One patient died before she was tested for aCL but she also had a false positive VDRL. Thus, all 12 patients with SLE with transverse myelitis had evidence of aPLA. We conclude that there is strong association between transverse myelitis in SLE and the presence of aPLA. PMID- 2313671 TI - Minocycline treatment for rheumatoid arthritis: an open dose finding study. AB - Ten patients with active definite or classical rheumatoid arthritis (RA) were treated with oral minocycline (maximal daily dose 400 mg) during 16 weeks in an open study. Seven patients reported side effects (in most cases vestibular) leading to premature discontinuation in one. Half of the efficacy variables improved significantly after 4 weeks of therapy. At the end of the study all variables were significantly changed compared with their pretreatment values. We conclude that minocycline may be beneficial in RA. This effect needs to be confirmed in controlled studies. PMID- 2313672 TI - Animal models of osteoarthritis. PMID- 2313673 TI - Transplacental transfer of human antinuclear antibodies in mice by injection of lupus IgG in pregnant animals. AB - Pregnant female Balb/c mice were injected with IgG fractions from patients with systemic lupus erythematosus, in order to study the in vivo passage of antinuclear antibodies (ANA) across the placenta. After injection of monospecific sera directed against nDNA, Sm, nRNP, Ro(SSA) and La(SSB), ANA were found in fetal circulation and trapped in the liver, spleen kidney and skin of fetus. Also, ANA were demonstrated in placental tissue and cord. The placental IgG-Fc receptors apparently played a major role in ANA entry into the fetus. Our study demonstrates that human ANA can be passively transferred into experimental animals to study their kinetics during pregnancy. PMID- 2313674 TI - Ketotifen prevents skin fibrosis in the tight skin mouse. AB - Mast cells in the skin of the tight-skin mouse show an enhanced degranulation compared to those of syngeneic litter mates. Oral treatment with ketotifen, an inhibitor of mast cell degranulation, at a dose comparable to that recommended for man, was associated with a decrease in both mast cell degranulation and in skin fibrosis, suggesting the potential for its use in human scleroderma. PMID- 2313675 TI - Antinuclear antibodies in arthritic and nonarthritic children with uveitis. AB - We determined whether a positive test for antinuclear antibodies correlated with uveitis only in children with juvenile rheumatoid arthritis (JRA) or whether they also represented a serologic marker for isolated idiopathic chronic uveitis in children. We conclude that the immunopathogenesis of uveitis associated with JRA is different from that of idiopathic chronic uveitis. PMID- 2313676 TI - Reliability of measurements of active and damaged joints in psoriatic arthritis. AB - Our aim was to test the reliability of clinical measurements in psoriatic arthritis. The study involved clinical assessments of inflammatory activity as well as damage in 10 patients with psoriatic arthritis seen at the psoriatic arthritis clinic. Five rheumatologists examined these patients according to a latin square design. For the clinical measurements of actively inflamed joints and damaged joints there was no significant observer effect. This suggests that these are reliable measurements. There was, however, significant observer effect in the radiologic assessment, and further refinement of the measurement is required. PMID- 2313677 TI - The synthesis and accumulation of fibronectin by human articular cartilage. AB - Fibronectin was extracted from cartilage under denaturing conditions at concentrations of 1.5 and 15 micrograms/g wet weight for normal and osteoarthritic cartilage, respectively (i.e., there was a 10-fold increase in osteoarthritic cartilage). Heterogeneity on ion exchange and gelatin affinity chromatography and on agarose electrophoresis was consistent with the suggestion that it interacts strongly with elements of proteoglycans. Aggregation of cartilage proteoglycan by addition of hyaluronic acid also aggregated the endogenous fibronectin. Synthesis of fibronectin was identified in explants of normal cartilage by immunoprecipitation and electrophoresis. We conclude that cartilage fibronectin is a normal component of human cartilage and a normal product of mature chondrocytes. PMID- 2313678 TI - Spontaneous osteoarthritis in rhesus macaques. II. Characterization of disease and morphometric studies. AB - From examination of the articular tissue of 35 animals from the Caribbean Primate Research Centre, we identified the epidemiological and histomorphometric features of the spontaneous osteoarthritis (OA) that affects the free-ranging rhesus macaques. The frequency of this disease increases with aging, and in females, with increased parity. Histological and morphological studies demonstrate that as in humans, the disease is characterized by persistence of the chondrocyte density typified by the cartilage of young animals. Owing to its epidemiologic and histologic resemblance to the disease in man, we conclude that degenerative arthritis affecting rhesus macaques provides a useful model for the study of factors contributing to the pathogenesis of OA. PMID- 2313679 TI - Coexistence of rheumatoid arthritis and a monoclonal CD4 T cell lymphoproliferative disorder. AB - A 33-year-old man developed seropositive rheumatoid arthritis (RA) followed soon after by a monoclonal lymphoproliferative disorder characterized by CD4 positive T lymphocytes in his peripheral blood, bone marrow and lymph nodes. Previous reports of polyarthritis in association with a T cell lymphoproliferative disorder have all involved the CD8 phenotype. PMID- 2313681 TI - Serous peritonitis in adult Still's syndrome. AB - Serous peritonitis may be an underrecognized feature of adult Still's syndrome. An illustrative case with pathologic findings is presented. Serous peritonitis generally occurs during an acute multisystem flare of Still's syndrome. Peritoneal signs, abdominal distension, and radiographic air fluid levels in the small bowel may suggest incomplete bowel obstruction. Corticosteroids and supportive management are often effective although surgical lysis of adhesions may be required. PMID- 2313680 TI - Acute blood pressure elevation can mimic arteriographic appearance of cerebral vasculitis--(a postpartum case with relative hypertension). AB - A 35-year-old woman presented 9 days postpartum with severe headache, arterial hypertension, and left parietal symptoms. A cerebral angiogram revealed widespread irregular areas of narrowing and dilatation, highly suggestive of vasculitis. The hypertension was treated successfully. A repeat angiogram 9 days later was almost completely normal. As this course is inconsistent with isolated cerebral vasculitis, and because the angiogram normalized with antihypertensive therapy, it is likely that the angiographic findings were secondary to hypertension. Experimental data in fact show that acute hypertension can produce areas of cerebrovascular spasm and dilatation. Recognition that angiographic findings suggestive of cerebral vasculitis are nonspecific and may be due to hypertension should prevent unnecessary treatment for vasculitis in such patients. PMID- 2313682 TI - Porphyrin ring source can alter the outer membrane protein profile of non-typable Haemophilus influenzae. AB - Porphyrin ring source appears to alter the outer membrane protein (OMP) profile of some, but not all, non-typable (NT) Haemophilus influenzae strains isolated from sputum. When haemin was replaced with protoporphyrin IX, 41% of strains examined produced increased amounts of a polypeptide of 84 Kda and new OMPs of either 120 or 150 Kda. Immunoblotting with paired patient's sera revealed that antibodies reactive with these proteins were present, demonstrating OMP antigenicity and expression in vivo and indicating that these isolates of NT H. influenzae may display an altered OMP phenotype when growing in the human lung. PMID- 2313683 TI - Estimation of structural anisotropy based on volume orientation. A new concept. AB - The quantification of anisotropy--its main direction and the degree of dispersion around it--is desirable in numerous research fields dealing with physical structures. Conventional methods are based on the orientation of interface elements. The results of these methods do not always agree with perceived anisotropy, and anisotropic structures do not necessarily turn out to be 'anisotropic' using these methods. In the present paper, we propose an alternative to curve and surface orientation, namely volume orientation. Using trabecular bone as an example of a two-phase anisotropic structure, the new concept is studied in some detail. In particular, a parametric method of estimating volume orientation from sections is presented and discussed. PMID- 2313684 TI - Ultrastructural preservation of nuclei and chromatin: improvement with low temperature methods. AB - The ultrastructure of chromatin has been examined in nuclei prepared by a variety of low-temperature methods. Embedding glutaraldehyde (GA)-fixed nuclei in Lowicryl K4M or K11M following dehydration by the progressive lowering of temperature (PLT) method, or in K11M following spray freezing and freeze substitution (FS), produces chromatin fibres that have, in situ, a diameter close to the in vivo state, and show internal structural details consistent with patterns of nucleosome packing previously observed only in preparations of isolated fibres. This is a temperature-dependent effect; fibres conventionally dehydrated and embedded in Lowicryl at 0 degrees C or in conventional epoxy resin at 60 degrees C have lower and less uniform diameters, and lack internal structural details. Of the techniques used, spray freezing followed by FS resulted in the most notable improvement over conventional methods. Inclusion of GA during FS of rapidly frozen, unfixed nuclei in methanol does not result in cross-linking of nuclear proteins. In acetone, however, cross-linking by GA occurs at -45 degrees C, or at lower temperatures if the water content of the acetone-based FS media is kept deliberately high. Substitution regimes employing GA alone or in combination with uranyl acetate and/or osmium tetroxide do not result in fibre morphologies comparable to either prefixed or unfixed nuclei substituted in additive-free substitution media. Whole fibroblasts show excellent preservation of nuclei and the nuclear/cytoplasmic interface after spray freezing followed by FS and low-temperature embedding. PMID- 2313685 TI - A quantitative interference light microscope study of human first trimester chorionic villi. AB - Using a Jamin-Lebedeff-type interference microscope an analysis of frozen sections of human first trimester chorionic villi reveals regional differences down to subcellular resolution. The evidence indicates compositional differences between villus cell types and shows that the syncytiotrophoblast is differentiated into at least three layers, one of which corresponds positionally to the previously described syncytioskeletal layer. Quantitative measurements have been made of specimen thickness, refractive index and dry mass of regions in the tissue. Local differences in syncytiotrophoblast have been noted with respect to the content of a population of organelles with distinctive optical properties. These may correspond to stored forms of steroid hormone or their precursors. PMID- 2313686 TI - Protocol for replantation and revascularization of digits and limbs. AB - This report was designed to aid the primary care physician who is confronted with traumatic amputations, and to suggest treatment and triage guidelines. Giant strides have been made in the past 25 years in the area of microsurgery. It is now possible to salvage a digit or limb that in earlier times would have been lost. The most important steps begin at out lying hospitals at which the patient is first evaluated. This exciting new area of surgery requires education and standardization of treatment to afford the patient the best care possible. PMID- 2313687 TI - Phencyclidine intoxication: a case report. PMID- 2313689 TI - Collective negotiation and antitrust: Part 3. Antitrust laws and your practice. PMID- 2313688 TI - Thoracic actinomycosis presenting as spinal cord compression. AB - A single case of thoracic actinomycosis presenting with spinal cord compression is described. The authors review the etiology, pathology, presentation and management of thoracic and vertebral actinomycosis. PMID- 2313690 TI - Medico-legal brief. Physician owes duty to other persons when he administers drugs to patients. PMID- 2313691 TI - Termini of Salmonella flagellin are disordered and become organized upon polymerization into flagellar filament. AB - The terminal regions of Salmonella flagellin are essential for polymerization to form the flagellar filament. It has recently been suggested, on the basis of results from circular dichroism spectroscopy and scanning calorimetry, that these regions are disordered in solution. We report here direct evidence for disorder and mobility in the terminal regions of flagellin using 400 MHz proton nuclear magnetic resonance (n.m.r.) spectroscopy. Comparison of the n.m.r. spectra of monomeric and polymeric flagellin shows that the terminal regions become organized when polymerized to form the filament. PMID- 2313692 TI - Identification of a conserved region common to cadherins and influenza strain A hemagglutinins. AB - Cadherins are a family of integral membrane glycoproteins that mediate homophilic, calcium-dependent cell adhesion in vertebrate species. The primary structures of six members of the cadherin family have recently been determined. The extracellular portion of these proteins is composed of five domains, the first of which is the most highly conserved among cadherins. Previous searches of protein sequence databases have revealed little or no sequence homology between cadherins and other proteins. Here we report that the first extracellular domain of cadherins exhibits substantial sequence homology with the amino termini of influenza strain A hemagglutinins. These regions of sequence homology have been shown to be functionally important in both cadherins and hemagglutinins. Our observations suggest that a functional domain of cadherins is conserved among other proteins. PMID- 2313693 TI - Crystals of the NC1 domain of human type IV collagen. AB - Crystals of the non-collagenous C-terminal region (NC1) of type IV collagen have been obtained from human placenta. These crystals diffract to 2.0 A, and belong to space group P22(1)2(1), with cell dimensions a = 81 A, b = 158 A, c = 138 A, alpha = beta = gamma = 90 degrees. The crystals contain one hexamer in the asymmetric unit; they are very stable with respect to X-rays. PMID- 2313695 TI - Crystallization of the rainbow trout (Salmo gairdneri) haemoglobin IV. AB - Crystals of rainbow trout (Salmo gairdneri) haemoglobin IV were grown in mini batches from a solution of ammonium sulphate. Large single crystals grew over five days and were up to 2 mm in length. X-ray diffraction experiments indicated a space group of C222(1) with unit cell dimensions of a = 85.3 A, b = 94.6 A and c = 105.7 A. The crystals diffract to better than 2.5 A but exhibit some mosaicity along the c axis. PMID- 2313694 TI - Crystallization and preliminary X-ray characterization of a soybean seed lipoxygenase. AB - An isoenzyme of soybean (Glycine max L. Merrill cv. Provar) lipoxygenase (EC 1.13.11.12) has been crystallized using the vapor diffusion method. Crystals were grown from solutions of the protein (7 mg/ml) using 10 to 20% (w/v) polyethylene glycol 8000 in citrate/phosphate buffer (pH 5.7) containing 0.5% (w/v) n-octyl beta-D-glucopyranoside. The crystals reached maximum dimensions of 0.3 mm x 0.2 mm x greater than 2 mm. The enzyme crystallized in space group C222(1) with unit cell dimensions a = 246 A, b = 193 A and c = 75 A. A calculated Vm value of 2.35 A3/dalton was obtained assuming two molecules per asymmetric unit. The density of the crystals was found to be 1.16 g/ml, which confirmed the presence of two molecules per asymmetric unit and indicated a solvent content of 47.5%. PMID- 2313696 TI - Length distributions of hemoglobin S fibers. AB - Electron microscopy of sickle cell hemoglobin fibers fixed at different times during gelation shows an exponential distribution of fiber lengths, with many short fibers and few long ones. The distribution does not change significantly with time as polymerization progresses. If this distribution of lengths reflects kinetic mechanism of fiber assembly, it complements information from studies of the progress of average properties of the polymers and, as has been done for other rod-like polymerizing systems, permits testing of models for the mechanism of fiber assembly. In this case, the results are consistent with the double nucleation model of Ferrone et al. or with a related alternative model based on fiber breakage. However, other possible causes of this microheterogeneity exist, including: breakage due to solution shearing of the long, rod-like, fibers; the presence of residual nuclei; equilibrium relations governing polymerization; and breakage of solid-like but weak gels that develop early and adhere to the grid. The arguments against the first three of these possibilities suggest that they are not responsible. However, breakage of entanglements or cross-links in a solid like and adherent gel is consistent with the distributions. PMID- 2313697 TI - Optimal heat-induced expression of the Drosophila hsp26 gene requires a promoter sequence containing (CT)n.(GA)n repeats. AB - We report here the analysis of the sequence requirements for the heat-induced expression of the Drosophila melanogaster hsp26 gene using germline transformation. Heat-induced expression is augmented fivefold by a homopurine/homopyrimidine region from -85 to -134 that is devoid of heat-shock elements but contains numerous (dC-dT).(dG-dA) repeats. Sequences within this interval have been shown to assume a nuclease S1-hypersensitive structure in vitro. In this paper, we extend those in vitro observations, demonstrating that the S1-hypersensitive structure is triple-helical H-DNA formed by a symmetric (dC dT).(dG-dA) sequence. Thus, the sequences that form H-DNA in vitro are also required in vivo for optimal hsp26 transcription. However, mutational analysis and diethylpyrocarbonate modification experiments in isolated nuclei suggest that the (dC-dT).(dG-dA) sequence does not form H-DNA in vivo and argue against a role for H-DNA in the heat-induced expression of hsp26. PMID- 2313699 TI - Molecular architecture of the neurofilament. II. Reassembly process of neurofilament L protein in vitro. AB - Reassembly of the neurofilament (NF) in vitro was studied by low-angle rotary shadowing electron microscopy. Various intermediate stages of the reassembly were reconstructed from the smallest molecular mass subunit (NF-L) under controlled reassembly conditions. NF-L in 6 M-urea took the form of spherical particles with a diameter of about 12 nm. NF-L aggregated into rodlets of 70 to 80 nm long in a low-salt solution at alkaline pH. By reducing the pH of the dialyzing solution to 6.6, a pair of rods was formed by association side-by-side. Increasing the temperature of low-salt solutions from 4 degrees C to 35 degrees C did not produce intermediate-sized filaments. The addition of Mg2+ to the dialyzing solution resulted in the formation of short intermediate-sized filaments even at 4 degrees C. Further dialysis of the short intermediate-sized filaments against reassembly solution containing both NaCl and MgCl2 at 37 degrees C failed to elongate them into longer filaments, suggesting that annealing does not contribute to the elongation of neurofilaments. Different roles for Mg+ and NaCl in neurofilament reassembly were indicated. While Mg2+ strengthened the lateral association between 70 to 80 nm rods, NaCl appeared to promote the end-to-end association of filaments preferentially. Longer filaments were formed by increasing the NaCl concentration. By dialyzing NF-L against a buffer containing 50 mM-NaCl in the absence of Mg2+, unraveled filaments were formed. The many unraveled filaments were composed of four 8 nm wide filaments, which have been called the subfilament or the protofibril. Time-course experiments of the reassembly were performed in the absence of Mg2+, in which condition the rate of neurofilament reassembly appeared to be reduced. Star-like clusters, about four protofibrils joined together at one end, were suggested to be the initial stage of the intermediate-sized filament formation. The following two-step elongation mechanism of neurofilaments was deduced from these results. The pairs of rods were added to the ends of the protofibrils of neurofilaments, and after all four protofibrils were elongated they were then packed into neurofilaments. Distribution of larger molecular mass subunits, NF-M and NF-H, was studied. Addition of NF-M or NF-H to NF-L did not change the assembly properties of neurofilaments. Unraveled filaments reconstituted from NF-L plus either NF-M or NF-H indicated that NF-M and NF-H are incorporated evenly into each protofibril. PMID- 2313698 TI - Molecular architecture of the neurofilament. I. Subunit arrangement of neurofilament L protein in the intermediate-sized filament. AB - Using the smallest subunit (NF-L) of a neurofilament and a glial fibrillary acidic protein, the subunit arrangement in intermediate filaments was studied by low-angle rotary shadowing. NF-L formed a pair of 70 to 80 nm rods in a low ionic strength solution at pH 6.8. Two 70 to 80 nm rods appeared to associate in an antiparallel manner with an overlap of about 55 nm, almost the same length as the alpha-helix-rich central rod domain of intermediate filament proteins. The overlap extended for three-beaded segments, present at 22 nm intervals along the pairs of rods. The observations that (1) 70 to 80 nm rods were a predominant structure in a low ionic strength solution at pH 8.5, (2) the molecular weights of the rod and the pair were measured by sedimentation equilibrium as 190,000 and 37,000 respectively, and (3) the rods formed from the trypsin-digested NF-L had a length of about 47 nm, indicated that the 70 to 80 nm rod is the four-chain complex and the pair of rods is the eight-chain complex. Similar structures were observed with glial fibrillary acidic protein, indicating that these oligomeric structures are common to other intermediate filament proteins. NF-L assembled into short intermediate-sized filaments upon dialysis against a low-salt solution containing 1 to 2 mM-MgCl2 at 4 degrees C. The majority of these short filaments possessed four or five-beaded segments, suggesting that the pair of rods were arranged in a half-staggered fashion in neurofilaments. On the basis of these observations, we propose the following model for the intermediate filament subunit arrangement. (1) The four-chain complex is the 70 to 80 nm rod, in which two coiled-coil molecules align in parallel and in register. (2) Two four-chain complexes form the eight-chain complex by associating in an antiparallel fashion with the overlap of the entire central rod domain. (3) The eight-chain complex is the building block of the intermediate filament. The eight-chain complexes are arranged in a half-staggered fashion within the intermediate filament. PMID- 2313700 TI - Electrostatic mechanism of chromatin folding. AB - We describe a theoretical analysis of cation binding in the nucleosome, and in chromatin as it folds, using Manning's polyelectrolyte theory. The theory accounts remarkably well, even quantitatively, both for the interaction of histone charges with DNA in chromatin, and for the essential features of the folding process. The degree of chromatin folding under different ion conditions is reliably predicted by the electrostatic free energy of DNA in the H1 binding site, which determines repulsions between linker DNA segments thus limiting how closely they may approach. The electrostatic free energy is a function of the ionic strength and the residual (unneutralized) DNA charge. Monovalent cations effect chromatin folding primarily by screening the residual charge whilst divalent or trivalent cations bind to DNA reducing its residual charge. The binding of H1 to the linker DNA considerably reduces its electrostatic free energy by displacing bound cations and reducing the residual charge. Thus, native chromatin folds at lower salt concentrations than does H1-depleted chromatin. We conclude that the mechanism of chromatin folding is primarily electrostatic in nature. In vivo ion conditions are such that chromatin is compact but H1 molecules are able to exchange freely, probably due to a low degree of salt induced dissociation. When H1 molecules exchange, transient local disruptions may occur in the chromatin filament due to repulsion of temporarily H1-free linker DNA from within the filament, such that chromatin "breathes". Thus, the cell can maintain its chromatin in a compact form and access to DNA for sequence-specific DNA-binding proteins and the transcription machinery is still possible. PMID- 2313701 TI - An investigation of oligopeptides linking domains in protein tertiary structures and possible candidates for general gene fusion. AB - Fifty-one examples of oligopeptides linking protein domains were extracted from the Brookhaven database of three-dimensional protein structures. In general, the peptides displayed specific characteristics in composition, conformation, hydrogen bonding, flexibility and the like. The entire database was then searched for pentapeptides that would optimize these natural linker properties. The oligopeptides found are suggested as general candidates to link protein molecules or domains through gene fusion. PMID- 2313703 TI - Evolution of protein cores. Constraints in point mutations as observed in globin tertiary structures. AB - The amino acid sequences of ten globin chain tertiary structures were aligned and structurally equivalenced by spatial superposition of main-chain C alpha atoms. A search was then performed for structurally equivalent residue pairs that were buried in the protein core and that had mutated but maintained similar unmutated environments. Residues with atoms in contact with such central residue pairs define their environments. Such examples of point mutations would represent in vivo site-directed mutagenesis as would be observed in evolution. A search for mutated but exposed equivalent central residues was also performed. The constraints placed on the characteristics of the mutated residues (e.g., side chain volume, polarity, radius of gyration) allow suggestions for the evolutionary modes of protein core and surface development as well as residue substitution guidelines to maintain structural stability in protein engineering and design. PMID- 2313702 TI - Novel method for the rapid evaluation of packing in protein structures. AB - There has been considerable effort to predict the structure of proteins from their amino acid sequences. A major problem in all prediction efforts has been that, short of a direct comparison with crystallographic co-ordinates, it is often difficult to evaluate the merit of a model, or "proposed" protein structure. Here, we present a method for evaluating proposed protein structures that does not require a structural model of complete atomic detail. Our method evaluates residue-residue packing density using a simplified model of the polypeptide chain where amino acids are represented as one, two (histidine, tyrosine and phenylalanine), or three (tryptophan) spheres. This method also gives a measure of the appropriateness of residue-residue contacts, thus giving a measure of the amino acid distribution throughout the protein. Amino acid packing and amino acid distribution, as evaluated by this technique, are consistent with the accuracy of model-built structures. We have been able to select the best structures from a set of combinatorially generated models using this method, and we anticipate that it will be useful as a general tool for model-building. PMID- 2313704 TI - Guidelines to research positions. AB - For nurses wishing to change the course of their careers, many opportunities are available for entering the field of research and can indicate an exciting prospect. Although research involves considerable organization and management, it offers the opportunity to publish findings, which will enhance your curriculum vita. Never undertake an investigation or treatment on a patient without medical back-up, and always put safety first. PMID- 2313705 TI - Resources for the visually impaired. AB - There is a vast network of agencies across the country that provide services or information to people with vision problems. Eyecare providers are a key way to provide information to this population. Resources outlining financial benefits for the visually impaired on the federal and state level are available. A small investment of time to write or call for resources is the first step in making referrals that may make a significant difference for patients. PMID- 2313706 TI - Graves' ophthalmopathy. AB - Graves' disease is an inflammatory condition affecting the thyroid gland and the eye. The triad of exophthalmos, goiter, and hyperthyroidism is classic Graves' disease. Each of the signs may appear in an individual patient, although separated by weeks, months, or years. The primary cause of Graves' disease is unknown and cannot be treated satisfactorily; however, the complications may be treated. PMID- 2313707 TI - Diagnosis and treatment of chronic postoperative bacterial endophthalmitis. AB - Bacterial endophthalmitis has been recognized as a significant cause of chronic, delayed-onset inflammation following extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens implantation. The diagnosis of chronic postoperative bacterial endophthalmitis should be suspected in any case of chronic, refractory inflammation following ECCE. Although successful treatment may require surgical intervention in some cases, others may respond to antibiotic therapy alone. PMID- 2313708 TI - Continuing education for the contact lens technician. PMID- 2313709 TI - Elements of medicine: water. PMID- 2313710 TI - Retinitis pigmentosa. AB - Retinitis pigmentosa is a subset of inherited diseases associated with progressive degeneration of the retina otherwise classified as retinal dystrophies. Clinically, patients have nyctalopia (night blindness), progressive visual field loss, and eventually loss of central vision. Patients with retinitis pigmentosa should be evaluated for other ocular conditions that may simulate the condition, as well as for systemic disorders. PMID- 2313711 TI - Phase I trials: a strategy of ongoing refinement. PMID- 2313712 TI - Carcinogenic effects of low-level ionizing radiation. PMID- 2313713 TI - Diet to reduce cholesterol: heart recommendations agree with NCI, DHHS. PMID- 2313714 TI - HDLs: heart boon but cancer signal? PMID- 2313715 TI - Experts continue their search for clues to cancer cluster in west central Phoenix. PMID- 2313716 TI - Cancer toll-free hotline proliferate in the United States. PMID- 2313717 TI - Evidence of association between plasma high-density lipoprotein cholesterol and risk factors for breast cancer. AB - Females in western societies have higher plasma levels of high-density lipoprotein cholesterol (HDL-C) than males. The difference in plasma lipids between the sexes is believed to contribute to differences in risk of heart disease. The evidence reviewed here demonstrates that plasma levels of HDL-C are also associated with factors influencing risk of breast cancer, a leading cause of death in women in western societies. Both breast cancer risk and HDL-C levels are higher in women who live in northern European countries than in those who live in Asia, in women who have never been pregnant compared with those who have, and in women of higher socioeconomic status. HDL-C levels are also affected by several other known or suspected factors in breast cancer risk; these include dietary fat intake, alcohol consumption, endogenous hormones, and premenopausal leanness. Increases in any of these factors are known to increase the level of HDL-C. Preliminary work has also shown HDL-C levels to be higher in subjects with mammographic dysplasia and a family history of breast cancer. Further, in serum free culture systems, HDL-C appears to possess biologic properties that may be relevant to carcinogenesis. In other areas, evidence of a relationship between increased HDL-C levels and increased breast cancer risk is either incomplete or contradictory. These areas include obesity (in the risk of postmenopausal breast cancer), use of exogenous hormones (oral contraceptives or postmenopausal estrogens), and physical exercise. In addition, both elevated and depressed levels of HDL-C have been reported in women with breast cancer. Our findings suggest an association between high HDL-C levels and the epidemiology of breast cancer risk. We recommend additional studies of plasma lipid level as a possible risk factor for this disease. PMID- 2313718 TI - Pharmacology and clinical toxicity of 4'-iodo-4'-deoxydoxorubicin: an example of successful application of pharmacokinetics to dose escalation in phase I trials. AB - In a prospective phase I trial involving 35 patients with metastatic carcinoma, we tested a pharmacokinetic strategy for guiding dose escalation of the anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX), a new analogue reported to be more potent and less toxic than doxorubicin. This strategy is potentially a safe and more rapid way of determining the maximum tolerated dose (MTD) of anticancer agents. Retrospective studies have shown that the total plasma drug exposure after a dose lethal to 10% of mice (LD10) is approximately equivalent to the total exposure produced in humans by the MTD. Thus, we intended to aim dose escalation in humans to achieve the area under the curve for I-DOX plasma concentration x time (AUC) equivalent to that produced in mice by an LD10. However, differences in I-DOX pharmacokinetics and metabolism in BDF1 mice and humans at the initial dose prevented immediate application of this strategy. Therefore, we escalated the dose by the modified Fibonacci scheme while investigating the pharmacology of I-DOX and its major plasma metabolite 4'-iodo 4'-deoxy-13-dihydrodoxorubicin (I-DOXOL). Plasma pharmacokinetics was characterized by rapid elimination and extensive metabolism of I-DOX to I-DOXOL. The ratio of I-DOXOL to I-DOX plasma AUC was 12.8 +/- 7.3 SD. The plasma pharmacokinetics of I-DOX and I-DOXOL were linear in the range of tested doses (2 90 mg/m2). The LD10 in mice was 6.8 mg/kg for I-DOXOL and 6 mg/kg for I-DOX, and the concentration of drug that inhibited by 50% (IC50) the growth of human granulocyte-macrophage colony-forming units (CFU-GM) was 80 nM for I-DOXOL and 50 nM for I-DOX. From these findings, we concluded that the toxic effects of I-DOX and I-DOXOL are equivalent and reset the pharmacokinetic target of escalation to the sum of I-DOX and I-DOXOL AUCs at I-DOX LD10. Then we safely applied pharmacokinetically guided escalation to determine the MTD (80 mg/m2). The plasma AUC of I-DOX and I-DOXOL at the human MTD is 71% of the AUC at mouse LD10. The only dose-limiting toxic effect was severe granulocytopenia. PMID- 2313720 TI - Exposure to dioxins as a risk factor for soft tissue sarcoma: a population-based case-control study. AB - In a case-control study including 237 cases with soft tissue sarcoma and 237 controls, previous jobs and exposures to different agents, including pesticides, were assessed. Exposure to phenoxyacetic acids or chlorophenols gave a statistically significant increased rate ratio (RR) of 1.80 [95% confidence interval (CI) = 1.02-3.18] for soft tissue sarcoma. Exposure to phenoxyacetic acids of all types gave a nonsignificantly increased RR of 1.34 (95% CI = 0.70 2.56). During the 1950s, exposure to 2,4,5-trichlorophenoxyacetic acid gave a threefold significantly increased risk. High-grade exposure to chlorophenols, which are also contaminated by dioxins, gave an RR of 5.25 (95% CI = 1.69-16.34). The increased risk was thus attributed to dioxin-contaminated phenoxyacetic acids or chlorophenols that gave an RR of 2.43 (95% CI = 1.30-4.54). PMID- 2313719 TI - Thyroid nodularity and chromosome aberrations among women in areas of high background radiation in China. AB - Thyroid nodularity following continuous low-dose radiation exposure in China was determined in 1,001 women aged 50-65 years who resided in areas of high background radiation (330 mR/yr) their entire lives, and in 1,005 comparison subjects exposed to normal levels of radiation (114 mR/yr). Cumulative doses to the thyroid were estimated to be of the order of 14 cGy and 5 cGy, respectively. Personal interviews and physical examinations were conducted, and measurements were made of serum thyroid hormone levels, urinary iodine concentrations, and chromosome aberrations in circulating lymphocytes. For all nodular disease, the prevalences in the high background and control areas were 9.5% and 9.3%, respectively. For single nodules, the prevalences were 7.4% in the high background area and 6.6% in the control area (prevalence ratio = 1.13; 95% confidence interval = 0.82-1.55). There were no differences found in serum levels of thyroid hormones. Women in the high background region, however, had significantly lower concentrations of urinary iodine and significantly higher frequencies of stable and unstable chromosome aberrations. Increased intake of allium vegetables such as garlic and onions was associated with a decreased risk of nodular disease, which seems consistent with experimental studies suggesting that allium compounds can inhibit tumor growth and proliferation. The prevalence of mild diffuse goiter was higher in the high background radiation region, perhaps related to a low dietary intake of iodine. These data suggest that continuous exposure to low-level radiation throughout life is unlikely to appreciably increase the risk of thyroid cancer. However, such exposure may cause chromosomal damage. PMID- 2313721 TI - Colonic hyperplasia and hyperproliferation induced by a nutritional stress diet with four components of Western-style diet. AB - We studied the effects of specific nutritional modifications on colonic epithelial cell proliferation in mice and rats. The nutritional stress diet developed for this study was based on the AIN (American Institute of Nutrition) 76A semisynthetic diet, modified to contain four suggested risk factors of the human Western-style diet: increased fat and phosphate and decreased calcium and vitamin D content. We fed diets to mice and rats for 12 weeks beginning at 3 weeks of age. Hyperplasia developed in both sigmoid and ascending colon of mice and rats with lengthening of colonic crypts. Hyperproliferation developed in the sigmoid colon of mice and rats, and in the ascending colon of rats, with increased [3H]thymidine-labeling of epithelial cells. Thus, in colonic mucosa, the nutritional stress diet, which included risk factors of a Western-style diet, induced changes that occur in carcinogen-induced rodent models and in humans who are at increased risk for colonic neoplasia. PMID- 2313722 TI - Damage to multicellular human H-2 glioma spheroids incubated with LAK cells: an ultrastructural study. AB - Local brain tumor therapy using lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) has not proved to be effective in preliminary clinical trials. One obstacle to effective use of this therapy is ignorance about the events that follow contact of the LAK cells with glioma tissue. We used multicellular spheroids grown from human glioma cell lines as targets to study, in vitro, the effect of LAK cells against three-dimensional glioma tissue. Here we describe the ultrastructural changes in spheroids of H-2 glioma cells incubated in pellets of LAK cells for up to 24 hours. In H-2 spheroids, cellular damage was not restricted to the effector cell-target cell (effector-target) contact; it extended farther, at least partly because of nonspecific changes in the spheroid micromilieu. Formation of cytoplasmic blebs, a characteristic effect of T cells, natural killer cells, and LAK cells on single target cells, also occurs in H-2 spheroids, and it is not limited to the effector-target contact area either. These findings suggest that LAK cells release membrane-damaging agents that remain active outside the effector-target area, in the micromilieu of H-2 spheroid tissue. PMID- 2313724 TI - In vivo antitumor activity of 9-[(2-phosphonylmethoxy)ethyl]-guanine and related phosphonate nucleotide analogues. AB - Phosphonylmethoxyalkylpurine analogues were evaluated for their antitumor activity in murine tumor models. Three compounds, (S)-9-[(3-hydroxy-2 phosphonylmethoxy)propyl]adenine (HPMPA), 9-[(2-phosphonylmethoxy)ethyl]adenine (PMEA), and 9-[(2-phosphonylmethoxy)ethyl]guanine (PMEG) were modestly active with treated versus control (T/C) values of 125%-175% versus intraperitoneal P388 leukemia, but were inactive versus intravenously implanted P388. The most active and most potent of the three was PMEG, which was also evaluated against subcutaneously (SC) implanted B16 melanoma. In confirmatory experiments, optimal therapy with PMEG yielded reproducible increases in life span (T/C values of 164% 170%) and delays in primary tumor growth (7.3- to 13.0-day T-C values). PMEG is representative of a new class of antitumor antimetabolites heretofore recognized only for their antiviral properties. PMID- 2313723 TI - Phorbol ester-induced, cell-cycle-specific, growth inhibition of human B-lymphoma cell lines. AB - The activation, growth, and differentiation of three B-cell- and one non-B-cell derived human lymphoma cell lines were examined after treatment with protein kinase C-activating phorbol esters. Treatment with these agents resulted in early activation events similar to those observed in normal B cells. However, in contrast to their growth-promoting effect on normal human B lymphocytes, exposure to these phorbol esters induced profound growth inhibition of the three B-cell derived lymphoma lines. Maximal inhibition was achieved within 24 hours of culture initiation and could be reversed if the phorbol ester was removed after 12, but not 20, hours in culture. Cell-cycle analysis of phorbol ester-treated lymphoma cells revealed a G1/S block in one line, whereas cells from the other two lines accumulated in G2/M. These data demonstrate that protein kinase C binding phorbol esters can interrupt the cell cycle in two places in actively dividing human B-lymphoma cells. These findings may prove valuable with regard to potential therapy of human malignant lymphomas. PMID- 2313725 TI - Light-induced breakdown of flavone acetic acid and xanthenone analogues in solution. PMID- 2313726 TI - Relationship of progesterone-receptor positivity in malignant breast tumors to reproductive status of women at tumor initiation--results from patients with possible radiation-induced tumors. PMID- 2313728 TI - Dose-intense adjuvant treatment of high-risk breast cancer. PMID- 2313727 TI - Proposals for evaluation of toxic effects associated with treatment of gliomas: a call for action. PMID- 2313729 TI - Herbicides and non-Hodgkin's lymphoma: new evidence from a study of Saskatchewan farmers. PMID- 2313730 TI - Scientists navigate Bermuda triangle of technology transfer. PMID- 2313731 TI - Preconception notion: childhood leukemia risk linked to paternal exposure. PMID- 2313732 TI - Killer antibodies enter clinical trial against ovarian cancer. PMID- 2313733 TI - Sixteen-week dose-intense chemotherapy in the adjuvant treatment of breast cancer. AB - Fifty-three women with breast cancer were treated with a new 16-week dose intense, chemotherapy regimen. Patients with operable breast cancer with 10 or more histologically positive axillary nodes were treated with this five-drug regimen that incorporated the concepts of weekly chemotherapy, sequential administration of antimetabolites, and continuous infusion of fluorouracil (5 FU). The chemotherapy regimen consisted of eight cycles (each of 2 wk duration) of 100 mg of cyclophosphamide/m2 orally on days 1-7, 40 mg of doxorubicin/m2 intravenous (IV) on day 1, 100 mg of methotrexate/m2 IV on day 1 with 10 mg of leucovorin rescue/m2 every 6 hours for six oral doses on day 2, 1 mg of vincristine IV on day 1, and 600 mg of 5-FU/m2 IV at hour 20 over 2 hours. A continuous infusion of 300 mg of 5-FU/m2 per day was given IV on days 8-9 of each 2-week cycle. The doses and schedule of drug administration were designed to minimize dosage reduction and treatment delay. At a median follow-up of 17 months, there have been eight relapses in the 53 patients. The actuarial 3-year disease-free survival is 80% (95% confidence interval, 62% to 90%). The major side effects were attributable to myelosuppression. Absolute neutrophil counts less than 250/microL were noted in 12 (23%) patients; seven patients (13%) required hospitalization for management of neutropenic fever. No treatment related deaths occurred. Ninety-four percent of the planned doses were administered, and only 5% of the courses were delayed because of toxic reactions. The encouraging therapeutic data, manageable side effects, and our ability to deliver over 90% of the planned doses provide the rationale for a phase III comparison of this new dose-intense regimen and standard chemotherapy in patients with operable disease and positive axillary nodes. PMID- 2313734 TI - Mortality study of Canadian male farm operators: non-Hodgkin's lymphoma mortality and agricultural practices in Saskatchewan. AB - A cohort study of the mortality experience (1971-1985) of male Saskatchewan farmers has been conducted. This study involved linkage of records of the almost 70,000 male farmers identified on the 1971 Census of Agriculture and the corresponding Census of Population to mortality records. Pesticide exposure indices for individual farm operators for the year 1970 were derived from the 1971 Census of Agriculture records. Although the cohort as a whole had no excess mortality for any specific causes of death, including non-Hodgkin's lymphoma, significant dose-response relationships were noted between risk of non-Hodgkin's lymphoma and acres sprayed in 1970 with herbicides, as well as with dollars spent on fuel and oil for farm purposes in 1970. Using Poisson regression modeling, we found that relative risks for the highest level of herbicide use (greater than or equal to 250 acres sprayed) and fuel purchased in 1970 (greater than or equal to $900) on farms less than 1,000 acres total area were 2.2 (95% confidence interval = 1.0-4.6) and 2.3 (95% confidence interval = 1.1-4.7), respectively. PMID- 2313735 TI - Highly specific prediction of antineoplastic drug resistance with an in vitro assay using suprapharmacologic drug exposures. AB - Bayes' theorem has been used to describe the relationship between the accuracy of a predictive test (posttest probability) and the overall incidence of what is being tested (pretest probability). Bayes' theorem indicates that laboratory assays will be accurate in the prediction of clinical drug resistance in tumors with high overall response rates (e.g., previously untreated breast cancer) only when the assays are extremely (greater than 98%) specific for drug resistance. We developed a highly specific drug-resistance assay in which human tumor colonies were cultured in soft agar and drugs were tested at high concentrations for long exposure times. Coefficients for concentration x time exceeded those reported in contemporaneous studies by about 100-fold. We reviewed 450 correlations between assay results and clinical response over an 8-year period. Results were analyzed by subsets, including different tumor histologies, single agents, and drug combinations. Extreme drug resistance (an assay result greater than or equal to SD below the median) was identified with greater than 99% specificity. Only one of 127 patients with tumors showing extreme drug resistance responded to chemotherapy. This negligible posttest probability of response was independent of pretest (expected) probability of response. Once this population of patients with tumors showing extreme drug resistance had been identified, posttest response probabilities for the remaining cohorts of patients varied according to both assay results and pretest response probabilities, precisely according to predictions based on Bayes' theorem. This finding allowed the construction of a nomogram for determining assay-predicted probability of response. PMID- 2313736 TI - Lymphoid dependency and cutaneous melanoma. PMID- 2313737 TI - Dermal absorption of the phenoxy herbicides 2,4-D, 2,4-D amine, 2,4-D isooctyl, and 2,4,5-T in rabbits, rats, rhesus monkeys, and humans: a cross-species comparison. AB - Dermal absorption of the 14C-ring-labeled phenoxy herbicides 2,4-D [(2,4 dichlorophenoxy)acetic acid], 2,4-D amine (2,4-dichlorophenoxyacetic acid dimethylamine), 2,4-D isooctyl (2,4-dichlorophenoxyacetic acid isooctyl ester), and 2,4,5-T amine (2,4,5-trichlorophenoxyacetic acid trimethylamine) was examined following topical applications of the herbicides to the back of rabbits, the back and tail of rats, the forearm and forehead of rhesus monkeys, and the forehead of human volunteers. The effect of three pesticide vehicles (water, acetone, and Esteron LV96) was also investigated. The total percent dermal absorption was calculated from the mean percent urinary recoveries from the animal tests and corrected for nonurinary excretion of the radiolabel using data from intramuscular (im) injections. The human data are reported without im correction. The reliability of animal data for modelling human dermal absorption of pesticides is highlighted. PMID- 2313738 TI - Effects of 1,3-dichloropropene on the kidney of Fisher 344 rats after pretreatment with diethyl maleate, buthionine sulfoximine, and aminooxyacetic acid. AB - Acute nephrotoxicity of cis/trans-1,3-dichloropropene (DCP) was assessed in male Fisher 344 rats. Pretreatment of rats with corn oil, aminooxyacetic acid (AOA), buthionine sulfoximine (BSO), or diethyl maleate (DEM) was given intraperitoneally 1 h or 4 h prior to injection of DCP. Doses of DCP were 0, 25, 50, and 75 mg/kg intraperitoneally (4-5 animals per dose/pretreatment group). Urine was collected for 24 h. Excretion of creatinine, phosphorus, protein, N acetylglucosaminidase (NAG), and the major metabolite of DCP, N-acetyl-S-(cis-3 chloroprop-2-enyl)-cysteine (3CNAC), was measured. Excretion of the metabolite, 3CNAC, increased in a dose-related manner from 0 to 50 mg/kg of DCP, but further increases were not seen at the 75 mg/kg dose. The pretreatments produced no alterations in the amounts of metabolite excreted when compared to corn oil controls. Zero-order metabolism or impaired metabolism is suggested to be occurring at high doses of DCP. The AOA pretreatment group showed no increase in the excretion of NAG, whereas other pretreatments (corn oil, BSO, DEM) showed elevations of NAG excretion at the highest DCP doses. AOA inhibits renal beta lyase, an enzyme that mediates cleavage of mercapturic acid metabolites to toxic products. Since NAG excretion was not elevated in response to DCP with AOA pretreatment and was not raised by pretreatments that deplete glutathione, it is suggested that nephrotoxic effects of DCP may be mediated through the mercapturic acid metabolites on the kidney, rather than due to glutathione depletion per se. PMID- 2313739 TI - Estrogen-induced thyroid follicular cell adenomas in C57BL/6 mice. AB - Diethylstilbestrol (DES) was fed chronically to C57BL/6 mice at concentrations of 0, 5, 10, 20, 40, 160, 320, or 640 ppb in order to define the dose-response curve for neoplastic responses. The incidence of thyroid follicular cell adenomas was higher in control females than in males and was increased at mid-level doses of DES, especially in males. None were found in mice fed 640 ppb DES, probably because these mice died from other causes before follicular cell adenomas had developed. In both sexes, DES fed at 160 or 320 ppb significantly shortened time to-onset of these tumors, and 40 ppb increased their probability late in life. It is concluded that DES has a causal relationship to thyroid neoplasia in C57BL/6 mice, and similarities between this and the human disease suggest that C57BL/6 mice may be an appropriate model for human thyroid neoplasia. PMID- 2313740 TI - Interactive effects of ozone and formaldehyde on the nasal respiratory lining epithelium in rats. AB - The combined effects on the nasal epithelium of mixtures of ozone and formaldehyde at cytotoxic and noncytotoxic concentrations were examined. Male Wistar rats were exposed by inhalation during 22 h/d for 3 consecutive days to 0.3, 1.0, or 3.0 ppm formaldehyde, or to 0.2, 0.4, or 0.8 ppm ozone, or to mixtures of 0.4 ppm ozone and 0.3, 1.0, or 3.0 ppm formaldehyde, or to 1.0 ppm formaldehyde and 0.2, 0.4, or 0.8 ppm ozone, or they were sham-exposed to clean air. The noses were examined for pathological changes at six standard cross levels by light microscopy and for epithelial cell proliferation by counting [3H methyl]thymidine-labeled cells at cross levels II and III. Ozone at 0.4 ppm or 0.8 ppm or formaldehyde at 3 ppm enhanced cell proliferation at cross level II at all locations, except for the epithelium of the septum, which was not affected by ozone. At cross level III ozone alone did not induce cell proliferation, but formaldehyde at 0.3 and 1 ppm tended to reduce cell proliferation while at 3 ppm proliferation was slightly stimulated. The combined exposure to 0.4 ppm ozone and 0.3 ppm formaldehyde induced less cell proliferation at cross levels II and III when compared with that of 0.4 ppm ozone alone. Less cell proliferation was also seen at cross level II when animals were exposed to 0.4 or 0.8 ppm ozone in combination with 1 ppm formaldehyde than when exposed to these ozone concentrations alone. A more than additive increase in cell proliferation was found at cross level II after exposure to 0.4 ppm ozone in combination with 3 ppm formaldehyde, and at cross level III in animals exposed to 0.4 ppm ozone and 1 or 3 ppm formaldehyde. Treatment-related histopathological nasal changes, such as disarrangement, loss of cilia, and hyper/metaplasia of the epithelium were seen at 0.2, 0.4, and 0.8 ppm ozone and at 3 ppm formaldehyde. Simultaneous exposure to both materials did not noticeably affect type, degree, and size of the microscopic nasal lesions. PMID- 2313741 TI - Effects of short-term, single and combined exposure to low-level NO2 and O3 on lung tissue enzyme activities in rats. AB - To examine the pulmonary effects of relatively low levels of NO2 and O3, and test for any possible interaction in their effects, we exposed 3-mo-old male Sprague Dawley rats, free of specific pathogens, to either filtered room air (control) or 1.20 ppm (2256 micrograms/m3) NO2, 0.30 ppm (588 micrograms/m3) O3, or a combination of the two oxidants continuously for 3 d. We studied a series of parameters in the lung, including lung weight, and enzyme activities related to NADPH generation, sulfhydryl metabolism, and cellular detoxification. The results showed that relative to control, exposure to NO2 caused small but nonsignificant changes in all the parameters; O3 caused significant increases in all the parameters except for superoxide dismutase; and a combination of NO2 and O3 caused increases in all the parameters, and the increases were greater than those caused by NO2 or O3 alone. Statistical analysis of the data showed that the effects of combined exposure were synergistic for 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase, glutathione reductase, and superoxide dismutase activities, and additive for glutathione peroxidase and disulfide reductase activities, but indifferent from those of O3 exposure for other enzyme activities. PMID- 2313743 TI - Management of the injured colon: evolving practice at an urban trauma center. AB - The records of 239 patients surviving more than 24 hours with full-thickness intraperitoneal colonic injuries over a 7-year period were reviewed. During the first 3 years, 29% (31/106) of the patients were managed by primary repair without colostomy. In the next 4 years, almost twice as many patients, 56% (75/133), with similar colonic trauma were treated without fecal diversion (p less than 0.05). Although there was no difference in the mean Trauma Score in the patients with primary repair in the two time periods, the Injury Severity Score (mean +/- sd) in the patients without colostomy in the later periods was significantly higher (17.8 +/- 2.1 vs. 20.2 +/- 5.1) (p less than 0.001). No patient suffered because of the increased incidence of primary repairs. These patients had five abdominal abscesses and only one leak, whereas the patients with colostomy had 15 intraperitoneal abscesses. Because of the safety when primary repair is performed, more liberal use of primary colonic repair following penetrating trauma is warranted. PMID- 2313742 TI - Effects of perfluoro-n-decanoic acid on the respiratory activity of isolated rat liver mitochondria. AB - The toxic responses of rats to a single dose of perfluorodecanoic acid (PFDA) include reduced food consumption, severe body weight loss ("wasting syndrome"), and hypothermia. Recent studies have suggested that some of these effects may be due to alterations of basic metabolic processes in animals treated with PFDA. In order to test this hypothesis the effects of PFDA on respiratory activity of isolated rat liver mitochondria were examined. PFDA concentrations up to 87.5 micrograms/ml produced a linear increase in oxygen consumption during state 4 (nonphosphorylating) respiration. This suggested uncoupling of electron transport and oxidative phosphorylation was supported by the observation that PFDA released mitochondrial state 3 respiration from inhibition by oligomycin and stimulated latent ATPase activity. Concentrations of PFDA greater than 87.5 micrograms/ml produced progressively less increase in state 4 oxygen consumption, and a single high concentrations (150 micrograms/ml) completely inhibited state 3 respiration and prevented the uncoupling effect of 2,4-dinitrophenol. These observations suggest that in addition to uncoupling electron transport and oxidative phosphorylation PFDA may affect other energy-transducing functions of liver mitochondria such as inhibiting electron transport. These effects on mitochondrial respiration may help to explain the "wasting syndrome" characteristic of PFDA toxicity. PMID- 2313744 TI - Effect of local and systemic burn microenvironment on neutrophil activation as assessed by complement receptor expression and morphology. AB - Previously, we documented that humoral factors, especially complement products, contained in burn wound blister fluid (BF) modulate normal neutrophil (PMN) function and metabolism. The goal of the current study was to examine the effects of the local (BF) and systemic (burn serum or plasma) burn microenvironment on PMN activation as assessed by complement receptor expression and morphology. Induction of CR1 (C3b) and CR3 (iC3b) receptor expression of normal PMNs after incubation in medium, BF, or plasma (serum) from healthy volunteers or burned patients was measured using monoclonal antibodies and flow cytometry. BF (10% v/v, 37 degrees C) induced 25% more CR1 receptor expression than control or burn plasma (p less than 0.05), while the levels of CR3 expression of PMNs incubated in BF (10% or 80% v/v at 37 degrees C) was more than 300% that found when the PMNs were incubated in medium, burn, or patient plasma (p less than 0.05). The electron microscopic appearance of PMNs incubated in these fluids documented that degranulation was greater when cells were incubated in BF than medium, control, or patient plasma. These results indicate that PMN activation (CR1 and CR3 expression) is greater in cells exposed to the local (BF) than the systemic (plasma) humoral microenvironment shortly after thermal injury. PMID- 2313745 TI - The use of cultured autologous epidermis in the treatment of extensive burn wounds. AB - Seventeen patients with deep second- and third-degree burn wounds have been grafted with cultured autologous epidermis. These epidermal cell sheets were cultivated according to the feeder layer technique as described by Rheinwald and Green. After dispase treatment and detachment from the culture vessel, the cell sheets, mounted on a polyamide mesh, were ready for grafting. Patients with wounds excised at an early stage, prepared with human cadaver allografts or synthetic dressings, showed a significantly better graft take than nonexcised, chronic granulating wounds which were grafted at a later stage (47% versus 15%; p less than 0.002). Sandwich treatment of expanded mesh autografts and cultured autograft overlay did not improve the graft take, although in some cases wound healing was accelerated. The graft take was inversely correlated with the age of the patient (p = 0.01), and showed a weak inverse correlation with the day of first (and subsequent) culture grafting (p = 0.07). Wound infection was the main cause of graft failure. Up to 4 years after grafting, the grafted areas showed continued stability and the regenerated skin became supple, smooth, and pliable. Hypertrophic scar formation was less than observed in comparable areas treated with meshed grafts. Wound contraction occurred approximately to the same extent as in split-thickness skin grafts. We emphasize that by a better control of wound infection the graft take, also in secondary-stage procedures, can significantly improve. PMID- 2313746 TI - Injuries during woodworking, home repairs, and construction. AB - Study was made of 495 consecutive primary care patients treated for woodworking, home repair, and wood-related construction injuries. Mean AIS was 1.2, and 6% were hospitalized. Estimated annual injury rate involving such activities is 3.3/1,000 residents. Fifty-eight per cent of injuries occurred at work. Overall, where complete data are available, 30% of injuries involved use of power equipment, with injury usually resulting from direct contact with the equipment. The lone exception was portable circular or "Skill" saws, with a large proportion of eye injuries from ejected sawdust. Use of non-power equipment was involved in 21% of injuries, and falls from ladders or other elevations 14%. Mean days of complete or partial disability for work, home, and recreational activities were 11.8, 10.4, and 13.3, with 79% of work disability occurring to persons who had not been hospitalized. PMID- 2313747 TI - Pressure wave injuries to the nervous system caused by high-energy missile extremity impact: Part I. Local and distant effects on the peripheral nervous system--a light and electron microscopic study on pigs. AB - Pigs were used for studies of effects on the peripheral nervous tissue of pressure waves induced by impact and passage through the left thigh of high energy missiles. The short-lasting pressure waves were demonstrated to move close to the speed of sound and to have a spectrum of high frequencies and large amplitudes. The sciatic nerve in the contralateral leg showed no hemorrhage or major deformation. Both immediately after the missile impact and after 48 hr the myelin sheaths in the contralateral sciatic nerve showed deformation. Myelin was bulging into the axon, dislocating the axoplasm. The nodes of Ranvier could be exposed to an increased extent. Electron microscopic examination revealed decreased number of microtubules immediately after the trauma, persisting even after 48 hr in the largest axon. Schwann cells showed, especially after 48 hr, signs of damage and swelling. Similar changes, although less extensive, were noticed in the phrenic nerves as well as in unmyelinated axons in both sciatic and phrenic nerves. It is concluded that a high-energy missile hit in the thigh of a pig, caused structurally demonstrable dislocations of myelin sheaths, and disarrangement of cytoskeleton and endoplasmic reticulum in axons as well as other signs of damage. The changes may interfere with the normal functions of peripheral and autonomic nerves. PMID- 2313748 TI - Pressure wave injuries to the nervous system caused by high-energy missile extremity impact: Part II. Distant effects on the central nervous system--a light and electron microscopic study on pigs. AB - The aim of the present study was to investigate if distant effects could be detected within the central nervous system after impact of a high-energy missile in the left thigh of young pigs. Pressure transducers implanted in various parts of the body of the animal, including the brain, recorded a short-lasting burst of oscillating pressure waves with high frequencies and large amplitudes, traversing the body tissue with a velocity of about that of sound in water (1,460 m/s). The distance between the point of impact and the brain and cervical spinal cord is in the range of 0.5 m. Macroscopic examination revealed that there was no gross brain tissue disruption or visible blood-brain barrier dysfunction. Light microscopic examination demonstrated myelin invaginations in the largest axons and shrinkage of axoplasm. Electron microscopic examination revealed a reduction in the number of microtubules, especially in the larger axons in the brainstem. Disintegration of Nissl substance, i.e., chromatolysis, was noticed after 48 hr in many Purkinje nerve cells in the cerebellum, concomitantly with the appearance of an increased frequency of association between lamellar bodies and mitochondria. Changes could also be observed in the cervical spinal cord and, at reduced frequency and extent, in the optic nerve and in other parts of the brain. These effects were evident within a few minutes after the trauma and persisted even 48 hr after the extremity injury. It is concluded that distant effects, likely to be caused by the oscillating high-frequency pressure waves, appear in the central nervous system after a high-energy missile extremity impact. PMID- 2313749 TI - Post-traumatic limb ischemia: prediction of final outcome by transcutaneous oxygen measurements in hyperbaric oxygen. AB - In limb injuries (amputation, laceration injuries, or compartment syndrome), a circulatory insufficiency with a total or subtotal ischemia may occur and jeopardize the result of reconstructive surgery. Transcutaneous oxygen monitoring has been shown to reflect tissue perfusion and has been advocated to predict the final outcome of major vascular trauma of the limb. Unfortunately, in normal atmospheric conditions, this test is not sufficiently discriminative; we evaluate the effect of hyperbaric oxygen on the efficiency of this test. 23 patients with major vascular trauma of the limbs were evaluated by clinical examination and transcutaneous oxygen pressure (PTCO2) measurements. Sixteen had arterial repair and seven had clinical evidence of peripheral ischemia without an arterial lesion. In normal air, the transcutaneous oxygen values in the traumatized limb, of these 23 patients, were significantly lower than in the nontraumatized limb. But neither the absolute PTCO2 value nor the ratio between the traumatized limb's PTCO2 and that of the nontraumatized one can predict the final outcome (amputation). In hyperbaric oxygen (2.5 ATA), this ratio is significantly higher in the group where the surgery will succeed than in the group where final amputation will be needed (81.2 +/- 26.0 vs. 15.2 +/- 13.1; p less than 0.01). The overall sensitivity and specificity of prediction of the limb's final outcome when the bilateral PTCO2 ratio in 2.5 ATA pure oxygen is less than 0.40, are 100% and 94%, respectively. But what is perhaps more interesting is that, when considering a ratio value of less than 0.20, amputation can be predicted with a 100% true predictive value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313750 TI - Supracondylar fractures of the femur. AB - Ninety-three supracondylar fractures of the femur treated with 95 degrees angulated condylar plates were retrospectively evaluated. Seventy-one patients were males and 22 were females; ages ranged from 15 to 80 years (mean, 46.9 years). Seventy-two patients were involved in traffic accidents; 44 of them were victims of motorcycle accidents. Twenty patients sustained open fractures. Fifty patients had associated injuries, 41 of them had multiple fractures. There were 13 patients referred for management of complications. The followup periods ranged from 1 to 10 years (4.6 years). Seventy-nine patients had excellent/good results. Eighty-one patients achieved sound union. Stiffness of knee, nonunion, delayed union, and infection were the major complications. Careful selection of the patients, adherence to the principles of anatomic reduction and rigid fixation, and early mobilization are essential for satisfactory outcomes. PMID- 2313751 TI - Factors affecting mortality rate with iliac vein injuries. AB - Over an 8-year period, 49 patients were treated for iliac vein injuries with 25 (51%) deaths. The iliac vein injuries and their mortality rates (MR) were: common iliac vein--40% (6/15), internal iliac vein--65% (9/14), external iliac vein--29% (4/14), and two or more iliac veins--100% (6/6). This MR (51%) was much higher than those (18% to 38%) found in other series. The factors associated with this significantly increased MR were: Trauma Score less than 11 (MR = 71% or 24/35), initial OR systolic BP less than 70 mm Hg (MR = 89% or 15/17), ISS greater than 28 (MR = 65% or 24/37), 10 or more units of blood in the first 24 hours (MR = 65% or 22/34), and no obtainable BP on admission to the ED (MR = 65% or 15/22). Although the overall calculated probability of survival (Ps) by TRISS methodology was 0.43, several deaths might have been prevented by more complete resuscitation including restoration of core temperature above 34 degrees or 35 degrees C, and by packing the pelvis and closing rather than allowing three or more separate additional hypotensive episodes to occur while attempting definitive control of bleeding vessels. PMID- 2313752 TI - A new technique for exposure of injuries at the confluence of the retrohepatic veins and the retrohepatic vena cava. AB - Because of difficulties in rapid exposure and control, injuries of the retrohepatic veins and retrohepatic vena cava continue to have mortality rates approaching 100%. Current strategies include shunt and finger fracture techniques, with controversy continuing over the optimal approach. We describe a new technique which involves mobilization of the liver by transecting the superhepatic vena cava, and affords a posterior approach to these injuries. Cadaveric dissection and clinical experience are described. PMID- 2313753 TI - Strangulation of the internal carotid artery by the hypoglossal nerve. AB - Various aspects of blunt trauma to the internal carotid artery (ICA) can be found in the literature. Lesions of the arterial wall of the ICA at its intersection with the hypoglossal nerve (CN XII) were observed in a limited number of surgically treated cases. The pathophysiology of the whiplash injury and the anatomic proximity of the crossing nerve to the lateral arterial wall suggest a further mechanism of vascular injury in this area. PMID- 2313754 TI - Results of venous interposition grafts in arterial injuries. AB - Controversy continues regarding the use of PTFE versus autogenous vein grafts in the repair of arterial injuries. This study was designed to evaluate the results of a large series of autogenous interposition vein grafts used for arterial trauma. The charts of 191 patients with 192 arterial injuries repaired with an autogenous vein graft were reviewed. Specific areas of interest included graft related complications such as thrombosis, infection, rupture, incidence of amputation, and mortality. Seventy-six per cent of the injuries were due to penetrating trauma. Forty-five per cent involved the upper and 51% the lower extremity. Shock (B. P. less than 80) occurred in one third of the patients. There were 23 (12%) graft-related complications. Sixteen (8.3%) of the grafts thrombosed. Three of these patients required an amputation and one a nephrectomy. Seven grafts (3.6%) became infected; all seven eventually ruptured. Five of these patients required an amputation. Eighteen patients (9.4%) required amputation; however, only eight (4.2%) of these cases were graft related. One patient died from non-graft-related multiple organ failure, establishing a mortality rate of 0.5%. Based on the data reported in this series, it is concluded that autogenous grafts continue to provide a safe, readily accessible, and effective means by which selected arterial injuries can be repaired. PMID- 2313755 TI - Frostbite: predisposing factors and predictors of poor outcome. AB - A retrospective review of 79 frostbite cases over a 10-year period at a major Northern Canadian hospital was performed. Factors predisposing to frostbite injury and predictors of a poor outcome were sought. Impaired cerebral function was found to be the major predisposing factor to frostbite injury. At the time of injury, 53% of patients were under the influence of alcohol and 16% were suffering from psychiatric illnesses. Lower extremity frostbite, infection, and delay in seeking medical attention were factors found to be associated with a poor outcome. PMID- 2313756 TI - Pediatric first rib fractures. AB - First rib fractures are associated with a high incidence of thoracic, vascular, abdominal, and central nervous system injuries. Usually reported in the adult population, first rib fractures are infrequently described in the pediatric population. We take this opportunity to describe six pediatric patients who sustained traumatic first rib fractures. Overall, five patients required operative intervention. Two patients sustained major vascular injuries which were detected on physical examination and confirmed by arch aortography. In view of the high percentage of patients with vascular injury, first rib fracture in a pediatric patient should prompt a search for major vascular injury. PMID- 2313757 TI - Emergency transport of AS-1 red cell units by pneumatic tube system. AB - We present a study in which 14 units of AS-1 red blood cells (AS-1RBC) were transported by the Trans-Logic 620 (Denver, CO) pneumatic tube system to determine whether the system could be used without risk of significant hemolysis. Using standard hematologic parameters we detected negligible hemolysis and conclude that the Trans-Logic 620 system can be used to transport AS-1RBC. This may provide time- and labor-saving benefits generalizable to more than 250 U.S. hospitals which presently operate the Trans-Logic 620. PMID- 2313758 TI - A traumatic splenic pseudocyst--historical review, diagnosis, and current mode of treatment. AB - A 30-year-old American Indian male with a history of chronic pancreatitis and prior blunt abdominal trauma was preoperatively diagnosed as having a splenic pseudocyst. The patient was successfully treated surgically with decapsulation of the pseudocyst instead of a splenectomy. PMID- 2313759 TI - Fatal iodine toxicity following surgical debridement of a hip wound: case report. AB - This report presents the case of a patient who expired 10 hours following and emergent hip-wound debridement where Betadine, a povidone iodine solution, was used to provide continuous postoperative wound irrigation. Toxic manifestations of systemic iodine absorption appeared to cause her demise. PMID- 2313760 TI - Symptomatic lead toxicity secondary to retained shotgun pellets: case report. AB - Symptomatic lead toxicity has only rarely been associated with retention of foreign bodies. Recently a patient was seen who had sustained a shotgun wound to the left upper extremity 10 years previously without apparent nerve injury at the time of injury. The patient was asymptomatic for 9 years. During the tenth year, classic symptoms of lead toxicity, as well as increased blood levels, were documented. Removal of the majority of the lead pellets resulted in substantial decrease in the serum lead level and improvement of symptoms. PMID- 2313761 TI - Tangential low-velocity missile wound of the head with acute subdural hematoma: case report. AB - Tangential missile wounds of the head without skull fracture are a known entity. Usually, references in the literature indicate that this type of injury results from a high-velocity missile impact. We present a case of a tangential missile head wound caused by a low-velocity missile. As the range of fire was short, the quantity of energy that might be released could be equated with that released by a high-velocity missile fired from a much longer range. This possibility should be brought to the attention of clinicians as an essential element in this pre treatment clinical evaluation. We propose a pathomechanical explanation for the development of the clinical state. PMID- 2313762 TI - Management of blunt injuries of the axillary artery and the neck of the humerus: case report. AB - Axillary artery injury, a rare vascular complication of fracture of the humeral neck, is rendered unique by the concomitant subluxation of the humeral head. A coordinated vascular and orthopaedic surgical approach is necessary to reconstruct both the shoulder joint and the artery. The operative techniques chosen may determine long-term outcome. PMID- 2313763 TI - Paraparesis following emergency room thoracotomy: case report. AB - Spinal cord ischemia complicating resuscitative aortic occlusion is reported in a patient requiring emergency thoracotomy and aortic cross-clamping following a stab wound to the heart. Paraparesis and ischemic myelopathy were documented in the absence of associated injury. The possible contribution of systemic hypotension to spinal cord ischemia following aortic occlusion is suggested. PMID- 2313764 TI - Traumatic occlusion of two radiocephalic fistulas: case reports and their management. AB - The number of ambulatory dialysis patients is increasing each year with a concomitant rise in extremity access fistulas and grafts. The anatomic location of these fistulas makes them particularly susceptible to traumatic occurrences. Management of traumatic occlusion of these fistulas becomes a critical issue in allowing continuing dialysis in these patients. Management of two such patients is presented. PMID- 2313765 TI - Diagnosis and prompt therapy of infected post-traumatic cavitary lung lesions. PMID- 2313766 TI - Working with heroin sniffers: clinical issues in preventing drug injection. AB - Preventing illicit drug injection would be the ideal point for preventing HIV infection and AIDS among illicit drug injectors. This paper reports on clinical issues that arose in a program for intranasal ("sniffer") heroin users who were at high risk of injecting drugs. Extensive field notes were kept by the staff of the project. A generalized mistrust of authorities, denial of problems associated with non-injected drug use, and ambivalence about injecting were the major issues that arose during subject recruitment and the group sessions. The staff underwent trial and error learning, both becoming more confident in working with heroin sniffers, and finding better results for later participants in the study. PMID- 2313767 TI - Improvement in psychological functioning among drug abusers: inpatient treatment compared to outpatient methadone maintenance. AB - A total of 68 opiate and cocaine abusers, receiving hospital-based, multimodal treatment for drug abuse in a 14 to 21-day program, and 47 patients newly admitted to methadone maintenance were compared on changes in psychological functioning, using a pretreatment-posttreatment design. Psychological changes were assessed by the Adjective Checklist, measuring the construct of "need". Inpatient treatment resulting in abstinence was associated with positive, meaningful, and significant changes in need pattern that were internally consistent. An equivalent amount of time on methadone maintenance outpatient treatment produced no improvement in psychological functioning, except that these patients evidenced increased dependency needs. Implications are discussed. PMID- 2313768 TI - Chemical aversion therapy in the treatment of cocaine dependence as part of a multimodal treatment program: treatment outcome. AB - A pilot feasibility study of chemical aversion therapy in the treatment of cocaine dependence as part of a multimodal treatment program was conducted at the Schick Shadel Hospital of Santa Barbara. Twenty (20) patients (9 treating for cocaine only and 11 treating for cocaine/alcohol), who primarily snorted cocaine, completed a program which included chemical aversion therapy to develop a conditioned aversion to the sight, smell, and taste of a cocaine substitute (tetracaine, mannitol, and quinine with Psychem. Ninety-five (95) percent of patients were followed up in six months with a total abstinence rate from cocaine of 56% (78% current abstinence of at least 30 days prior to follow-up) in the cocaine only group and total abstinence from cocaine of 70% (also 70% current abstinence) for the cocaine/alcohol group. Ninety (90) percent were followed up at 18 months. Thirty eight (38) percent of the cocaine only group had been totally abstinent (75% were currently abstinent). Fifty (50) percent of the cocaine/alcohol group had been totally abstinent (80% were currently abstinent). Validation of results was obtained from "significant others" for 90% of patients. PMID- 2313769 TI - Depressive symptoms during buprenorphine treatment of opioid abusers. AB - Among 40 opioid addicts treated as outpatients with sublingual buprenorphine (2-8 mg daily) for a month, depressive symptoms significantly decreased in the 19 who were depressed at intake to treatment. PMID- 2313770 TI - Detoxification with phenobarbital of alprazolam-dependent polysubstance abusers. AB - Alprazolam appears to have an abuse liability among opiate addicts, and detoxification can be prolonged. The authors describe experience with five methadone maintenance patients who were polysubstance abusers and were admitted specifically for detoxification from alprazolam dependence. Phenobarbital in tapering doses adequately suppressed withdrawal symptoms and shortened hospitalization. PMID- 2313771 TI - Rubella immunity in chemically dependent adolescent females. AB - Congenital rubella syndrome continues to be a problem in this country because of the continued existence of a substantial susceptibility to rubella in young women of childbearing age. The objectives of this study were to determine the percentage of chemically dependent adolescent women in a residential treatment center at risk for rubella infection and to correlate their immune status with history of immunization. Although only one individual was reported as not having been vaccinated for rubella, 12.4% of the 129 subjects were found to be nonimmune by titer. No statistical relationship was found between self- or parent-reported immunization status and actual titer finding. Of the 16 women found to be not immune, only 56% were successfully vaccinated. Patient history appears to be of little value in establishing immunization status in this population. We recommend vaccination of young women in residential treatment centers who do not have documented histories of vaccination. PMID- 2313773 TI - Chasing the dragon: the smoking of heroin and cocaine. PMID- 2313772 TI - The ABCs of awareness: a multimodal approach to relapse prevention and intervention--the College Hill Medical Center program. PMID- 2313774 TI - Childhood idiopathic thrombocytopenic purpura: report of 60 cases from Kuwait. AB - Sixty children with idiopathic thrombocytopenic purpura (ITP) were admitted to a regional hospital in Kuwait over a 6-year period. A high annual incidence of ITP (12.5/10(5] was noted, probably related to viral infections during the period of the study. Forty-one were patients with acute ITP and 19 with chronic ITP. The initial treatment varied: corticosteroids were given in 33 cases, no therapy in 23 cases, and intravenous gamma globulin (IVGG) in four cases. Splenectomy was carried out in two children, of whom one died 2 years later as a result of septicaemia. This study showed that conservative management can be adopted in mild cases of ITP and active measurements should be reserved for patients presenting with moderate-severe mucocutaneous bleeding and significant thrombocytopenia. PMID- 2313775 TI - Growth factors in human milk. PMID- 2313776 TI - Half a decade of neonatal sepsis, Riyadh, Saudi Arabia. AB - In a retrospective study to determine the pattern of neonatal sepsis, all cases admitted to the Neonatal Intensive Care Unit (NICU) between October 1983 and July 1988 at King Khalid University Hospital, in Riyadh were studied. During the review period there were a total of 2117 admissions to the NICU. Of those 1252 (59 per cent) underwent septic screening sometimes during their stay in the NICU. The number of babies with proven bacteremia, i.e.; positive blood and or cerebrospinal fluid culture was 190 (15 per cent). Gram-positive organisms were cultured from 132 (69 per cent) and Gram-negative organisms from 47 (25 per cent) of the babies. The single most frequent organism was Staphylococcus epidermidis accounting for 36 per cent (58/190) of all proven cases. These results differ appreciably from other studies reported previously from Riyadh as well as from some other parts of the world, and stress the need to recognize Staphylococcus epidermidis as an increasingly important pathogen in the newborn nursery. PMID- 2313777 TI - Viral aetiology of acute respiratory infections in children in north India. AB - Two hundred and thirty children clinically diagnosed as suffering from acute respiratory infection were tested for four major groups of viral aetiological agents, i.e. influenza para-influenza, respiratory syncytial virus (RSV) and adenoviruses using indirect immunofluorescence technique. At least one of the respiratory viruses was identified in 51 (22 per cent) specimens, which included influenza A in 6 (3 per cent), influenza B in 3 (1 per cent), para-influenza type 1 in 3 (1 per cent), para-influenza type 3 in 13 (6 per cent), RSV in 11 (5 per cent) adenovirus in 12 (5 per cent), and dual virus infections in 3 (1 per cent) cases. Maximum number of virus identification was noted in children below 1 year of age, particularly infection with RSV followed by para-influenza and adenoviruses. Value of rapid diagnosis by indirect immunofluorescence technique is stressed. PMID- 2313778 TI - Determinants for breast feeding and bottle feeding in Botswana. AB - In the Botswana Primary Health Care Survey 1983-84 data on breast and bottle feeding were collected as well as characteristics of households, mothers, and children. The country-wide median breast-feeding duration was 1 year and 7 months, with a tendency towards shorter duration in the urban areas. Better hygienic conditions, higher education of the mother, and wage employment of the mothers were associated with shorter breast-feeding duration. Similarly, the risk of starting bottle feeding was higher in households with better hygienic conditions. However, a substantial proportion of the bottle feeding took place in households lacking piped water indoors. These data may indicate a current shift from traditional feeding patterns towards shorter breast feeding and introduction of bottle feeding, starting among well-off families, but also threatening the health of children in less privileged conditions. The association with maternal factors such as type of occupation calls for breast feeding promotion including improved conditions for the salary employed mothers. PMID- 2313779 TI - Risk assessment in birth asphyxia. AB - In developing countries the need for a risk approach in neonatology is obvious because of a high birth rate, high neonatal mortality rate, and limited availability of resources. Quantification of risk, with selected antepartum, intrapartum factors, clinical, and post-mortem findings was done by calculating odds ratio, attributable risk, and 95 per cent confidence limits in 1811 babies, 541 of which were asphyxiated. Primigravidity, history of perinatal death, pregnancy induced hypertension, and antepartum haemorrhage carried higher risk. Abnormal fetal heart rate and meconium passage in amniotic fluid correctly predicted high risk of birth asphyxia. Decreasing risk in premature/low birth weight babies without increase in abdominal deliveries suggested that caesarean sections were unnecessary in preterm deliveries. Clinical monitoring of asphyxiated newborns was adequate enough. PMID- 2313780 TI - The symphysis-fundus height graph and fetal growth retardation: gimmick or useful clinical tool? PMID- 2313781 TI - Videodisc technology: teaching underserved populations about infant feeding. PMID- 2313782 TI - Beta-thalassemia/haemoglobin E disease in Vietnam. AB - A clinical and haematological study of 75 patients with beta thalassemia/haemoglobin E (HbE) in Vietnam is described. The clinical picture is similar to thalassemia major. Anemia is often severe, haemoglobin was 5.0 +/- 1.6 g/dl. Splenomegaly was almost consistently detected. Haemochromatosis was clear. Both red cell indices and morphology showed hypochromicity and microcytosis, the MCH was 23.3 +/- 2.9 pg, the MCV was 81.5 +/- 11 fl; anisocytosis, poiklocytosis, tear drop cells, leptocytosis, target cells, and polychromasia were always observed. The osmotic fragility of erythrocytes was increased. The erythrocytic lifespan was shortened, about 7-15 days and the erythrocytes were destroyed in the spleen in 63 per cent of cases. Depending on whether it was beta(+) thalassemia/HbE or beta(0)-thalassemia/HbE, HbF ranged from 22.8 +/- 7.2 to 57 +/ 12.7 per cent; HbE from 30.1 +/- 12.2 to 42.7 +/- 13 per cent; and HbA1 was decreased down to from only 46.8 +/- 13.5 to 0 per cent. PMID- 2313783 TI - Seizures associated with fever in children. PMID- 2313784 TI - Physician referral patterns for stutterers. AB - Many children who stutter initially seek guidance from their pediatricians. Pediatricians often do not refer stutterers for speech therapy. We present a brief analysis of pediatricians' views regarding stuttering, as well as their exposure to patients who stutter. We present a practical approach to children who stutter. PMID- 2313785 TI - Evaluation of the Words with Ipsilateral Competition test. AB - The Words with Ipsilateral Competition test was examined for test-retest reliability, item difficulty, and list differences. Results revealed that: (a) many test words contributed little or nothing to the overall test results; (b) list 1 and list 3 were not homogeneous in terms of item difficulty; (c) test performance was influenced by list order, and (d) test-retest reliability correlations were low but significant with test-retest differences ranging from 12% to 32%. Based on the present findings, it was recommended that use of the Words with Ipsilateral Competition test be discontinued until the test is revised. PMID- 2313786 TI - Scanning electron microscopy of tympanic membrane epithelium during in vitro migration. AB - The en masse locomotion in tissue culture of stratified squamous epithelium of the tympanic membrane and cholesteatoma is a unique feature of these epithelia. A scanning electron microscopy study of cultures was carried out to seek features of surface architecture that might throw light on this special activity. Differences from cultures of non-migratory stratified squamous epithelium include the following: numerous lamellae emanating from the top surface of cells at the leading edge, a ridge of spent leading edge cells behind that edge, a cap of keratin behind the latter and large balloon-like swelling of cells is prevalent in the trailing edge. It is suggested that differentiation of migrating stratified squamous epithelium in tissue culture is towards specialized cells active in migration as shown by the leading and trailing edge cells, as well as towards keratinization as shown by the keratin cap. PMID- 2313787 TI - Vocal function following vertical hemilaryngectomy: a preliminary investigation. AB - Seven consecutive male patients who received a vertical hemilaryngectomy were examined for vocal function employing video-stroboscopic, aerodynamic and acoustic measurement techniques. The results of this preliminary investigation suggest that with the group of patients studied, vocal quality was rated as "rough", "breathy" and "constricted". While large variability was noted between individuals, the general tendencies for the group included: (a) incomplete glottic closure; (b) supraglottic structures (ventricular folds, arytenoids) fulfilled or aided vibratory action of the remaining fold; (c) high average transglottal airflow; (d) reduced maximum phonation time; (e) high and more variable vocal frequency positioned near the top of the frequency range; (f) a lower, more variable, and restricted vocal intensity range, and (g) a reduced vocal fold diadochokinetic (vocal fold opening and closing action) rate. We are currently attempting to determine factors related to individual patient strategies for using either glottic or supraglottic valving during phonation. PMID- 2313789 TI - Avoiding small bony fragments following stapedectomy. PMID- 2313788 TI - Tuberculosis of a periglandular lymphnode presenting as a parotid tumor. AB - The presentation of tuberculosis as isolated cervical adenopathy is not a common entity. The presentation of this disease as a parotid mass has rarely been reported. In most instances, direct parenchymal involvement exists, although involvement of intraglandular lymphnodes has also been reported. In most cases, an initial misdiagnosis of a parotid tumor, usually a pleomorphic adenoma, was made. We report a case of a 57-year-old patient with a left parotid mass of two years' duration. The patient was referred because of the development of firm, nontender, ipsilateral cervical adenopathy, suggesting possible malignancy. The course of the disease, diagnosis, and treatment are reported. The relevant literature is reviewed. PMID- 2313790 TI - Fixing external nasal splint with Tegaderm i.v. dressing. PMID- 2313791 TI - Anatomical relationship between the intrarenal arteries and the kidney collecting system. AB - The anatomical relationship between the intrarenal arteries and the renal collecting system was studied in 82, 3-dimensional endocasts. Some anatomical details that have importance for urologists were observed. The arterial supply related to the upper caliceal group arises from 2 arteries that encircle these calices (in 86.6% 1 trunk originated from the anterior division and 1 from the posterior division of the renal artery). The artery to the mid kidney courses horizontally in the mid renal pelvis in 64.6% of the cases while the arterial supply to the inferior pole (front and back) arises from the inferior segmental artery of the anterior division in 62.2%. The posterior segmental artery is related to the upper infundibulum or to the junction of the pelvis with the upper calix in 57.3% of the cases and to the middle posterior aspect of the renal pelvis in 42.7%. PMID- 2313792 TI - Attempted nonoperative management of blunt renal lacerations extending through the corticomedullary junction: the short-term and long-term sequelae. AB - A total of 50 patients who sustained a renal laceration extending through the corticomedullary junction following blunt trauma underwent an attempt at nonoperative (expectant) management of the urological injury. Of the patients 18% could not be stabilized and they subsequently underwent emergency laparotomy. Among our stabilized patients 2 major categories existed: 1) 30 patients with vascularized renal fragments and 2) 11 in whom a fragment of the kidney was devascularized. A statistically significant difference in the length of hospital stay (p equals 0.01) and the need for delayed surgical intervention (p less than 0.001) was noted between the 2 groups. We recommend that the physician must have a heightened awareness of probable complications in patients with major renal lacerations associated with devitalized fragments and suggest that early surgical management should be considered. PMID- 2313793 TI - Decreased urinary uronic acid levels in individuals with interstitial cystitis. AB - The pathogenesis of interstitial cystitis currently is unknown. A possible etiology is that the transitional epithelium is defective, leading to molecular leaks that initiate the disease complex. An important surface defense mechanism is the glycosaminoglycans or polysaccharides that line the bladder epithelium and act as a nonspecific antiadherence factor blocking access of bacteria, microcrystals, proteins and ions to the underlying transitional cells. We examined the excretion of urinary macromolecular uronic acid and glycosaminoglycans in normal individuals and those with interstitial cystitis. A total of 37 controls had a mean macromolecular uronic acid level of 56 nmol. per mg. creatinine, compared to 40.2 nmol. per mg. creatinine in 43 patients with active disease (differences were significant, p equals 0.03). The median excretions of glycosaminoglycan uronate for controls and patients were 15.1 and 11.1 nmol. per mg. creatinine, respectively. (There was an over-all tendency to decrease excretion in patients with a p value of 0.06.) Specimens obtained at cystoscopy from patients with active interstitial cystitis had ureteral macromolecular uronic acid levels of 40.5 nmol. uronate per mg. creatinine compared to 43.6 nmol. uronate per mg. creatinine from the bladder. Interstitial cystitis patients had 16.0 nmol. glycosaminoglycan uronate per mg. creatinine compared to 14.6 nmol. per mg. creatinine in normal controls. Neither of these differences was statistically significant. It would appear that there is a tendency to lower macromolecular uronic acid and polysaccharide excretion in individuals afflicted with this syndrome. PMID- 2313794 TI - Computerized morphonuclear cell image analyses of malignant disease in bladder tissues. AB - We analyzed the relationship between several morphonuclear parameters related to nuclear size, densitometry (deoxyribonucleic acid content and ploidy) and the chromatin pattern versus the histopathological grading of 46 bladder cancer samples graded according to the World Health Organization classification. We used a SAMBA 200 cell image processor with software allowing for the discrimination of 15 different parameters on Feulgen-stained imprint smears. In addition, we set up preliminary data banks that enable objective and reproducible grading of unknown cases. This approach must be validated in a large series of cases to create an expert system for bladder malignancy diagnosis. PMID- 2313795 TI - Human chorionic gonadotropin, neuron specific enolase and deoxyribonucleic acid flow cytometry in patients with high grade bladder carcinoma. AB - Biopsies from 64 patients with transitional cell carcinoma of the bladder (World Health Organization grade 3 and undifferentiated) were studied with deoxyribonucleic acid flow cytometry of fresh tissue and immunohistochemical staining on the histopathological slides for the presence of neuron specific enolase and human chorionic gonadotropin. No correlation was found among the presence of neuron specific enolase or human chorionic gonadotropin and T category, deoxyribonucleic acid ploidy, percentage of cells in the S phase, presence of metastatic disease or response to therapy. The prognosis for patients with muscle invasive disease and tumors positive for neuron specific enolase or human chorionic gonadotropin was similar to that for patients with tumors negative for these substances. When a possible new marker or prognostic factor is evaluated, it is important to investigate whether the new marker adds information on prognosis to what already is known by established standard methods. Further studies are needed to evaluate the clinical importance of human chorionic gonadotropin (and neuron specific enolase) as a marker in urothelial cancer with regard to prognosis and response to therapy. PMID- 2313796 TI - The response of patients with superficial bladder cancer to a second course of intravesical bacillus Calmette-Guerin. AB - Of 347 patients who received an initial 6-week course of intravesical bacillus Calmette-Guerin for superficial transitional cell carcinoma of the bladder 28 (8%) were treated with another course. Subsequent progression of disease (muscle infiltration, metastasis or local progression) occurred in 13 patients (46%). Of the 15 patients (54%) without progression 10 (36%) had a complete response and 5 (33%) had new tumors, and they were rendered free of disease after transurethral resection. The median duration of response to course 1 of bacillus Calmette Guerin was shorter for patients with disease progression after course 2 than for those with no progression (15 and 27 months, respectively, p equals 0.05). The median followup after course 2 was 31.2 months (range 15.6 to 56.4 months). The median interval between courses 1 and 2 of intravesical bacillus Calmette-Guerin was 21.6 months (range 3.6 to 78.8 months). The interval from course 2 of bacillus Calmette-Guerin to progression correlated with the duration of response to course 1 of treatment (p equals 0.01). It appears that a subsequent treatment with bacillus Calmette-Guerin is most likely to be useful in patients who have a sustained response to the initial treatment. PMID- 2313797 TI - Phase I and pharmacology study of intravesical mitoxantrone for recurrent superficial bladder tumors. AB - A phase 1 study of intravesical mitoxantrone was done in patients with superficial bladder tumors recurrent after previous intravesical therapy. Mitoxantrone (5 to 10.5 mg.) was instilled in the bladder via catheter and was left in situ for 2 hours. Each patient received 6 treatments at 1-week intervals. Pharmacology studies were conducted in a subset of consenting patients. Dysuria, urinary frequency and hematuria were dose-limiting at 10 to 10.5 mg., the dose recommended for our phase 2 studies. One patient treated with 7.5 mg. mitoxantrone had bladder contracture after severe bladder injury caused by the drug. The interval free of recurrence increased in 5 of 8 patients treated with 10 to 10.5 mg. mitoxantrone and in 6 of 19 treated at lower dose levels. One patient who had residual evaluable tumor in the bladder at treatment experienced a complete remission for 16 months. Only 1 of 18 patients who underwent pharmacology studies had any mitoxantrone detectable in the blood after intravesical administration. This patient had severe irritative symptoms at treatment. No systemic toxicity was noted in any patient. Of the mitoxantrone instilled into the bladder 33 to 100% (mean 75%) was recovered in the specimen voided at the end of treatment. In summary, intravesical mitoxantrone is reasonably well tolerated and should be studied further at a dose of 10 mg. per week for 6 weeks. Caution should be exercised, since bladder contracture was seen in 1 patient. Systemic absorption and toxicity are negligible. PMID- 2313798 TI - Clinical evidence for and implications of the multistep development of prostate cancer. AB - Based upon a large body of experimental and clinical data, it is evident that multiple malignant events are necessary for a normal cell to give rise to a fully malignant cancer cell. A critical issue with regard to human prostatic carcinogenesis is the clinical significance of the large number of cancers that are present histologically in the elderly male prostate gland. A possibility is that these histological prostate cancers already have undergone all of the malignant events necessary to produce clinically manifest cancer and, thus, only further tumor growth is required to produce a clinical tumor. Alternatively, these histological cancers may have undergone some but not all of the events necessary to produce clinical disease and, therefore, despite host longevity the cancer will remain clinically silent as long as no further malignant changes occur. This issue has importance clinically with respect to the diagnosis, therapy and possible prevention of prostatic cancer. Clinical observations and the mathematical relationship between prostate cancer prevalence and host age (time) support the fact that, in addition to growth, histological prostate cancer requires further malignant events to produce clinical disease. A better understanding of the events involved in prostate cancer development will be necessary to have a greater impact on this disease in the future. PMID- 2313799 TI - Treatment of post-orchiectomy hot flashes with transdermal administration of clonidine. AB - The occurrence of hot flashes in men after bilateral orchiectomy for prostatic carcinoma can be bothersome and difficult to treat. Transdermal clonidine was administered to 7 patients with such symptoms. In 3 patients the hot flashes were ablated and in the remaining 4 the number and frequency of attacks were considerably reduced. No significant side effects were encountered. We suggest that transdermal clonidine (0.1 mg.) administered weekly can safely control undesirable hot flashes in men after bilateral orchiectomy. PMID- 2313800 TI - Anastomotic strictures following radical prostatectomy: risk factors and management. AB - Stricture of the anastomosis between the bladder neck and membranous urethra after radical prostatectomy can cause significant voiding dysfunction. Of 156 patients undergoing radical prostatectomy for localized prostatic carcinoma 18 had anastomotic stricture for an over-all incidence of 11.5%. The risk factors for anastomotic stricture and the treatment outcome in these patients were analyzed. Excessive intraoperative blood loss, extravasation of urine at the anastomotic site and a prior transurethral prostatic operation significantly contributed to the development of stricture. More than half of the patients did not respond to simple dilation alone. Cold knife incision of the stricture by itself was effective in only 62% of the patients. The remaining patients required periodic dilation to maintain an adequate urine flow. Incision of the stricture with electrocautery resulted in urinary incontinence in all patients. PMID- 2313801 TI - Ligation of crura penis for corporeal length adjustment in cases of short rod like penile prostheses. AB - A technique for correction of penile deformity caused by a short rod-like penile prosthesis is described. This procedure was done in 4 patients and corrected the deformity efficiently, allowing for satisfactory sexual function. PMID- 2313802 TI - Suprapubic approach for bilateral orchiectomy and placement of testicular prostheses. PMID- 2313803 TI - Ectopic ureter presenting as a psoas abscess. AB - Psoas abscesses are uncommon infections whose etiology may be primary or secondary. We report on a boy with ureteral ectopia presenting as a secondary psoas abscess. The diagnosis of a psoas abscess is protean and should be considered in all patients, particularly children, who present with acute thigh or hip pain and fever. PMID- 2313804 TI - Ureterosigmoidostomy: an outdated approach to bladder exstrophy? AB - Long-term results among 46 children with ureterosigmoidostomy are presented. The indication for ureterosigmoidostomy had been bladder exstrophy in 40 patients, incontinent epispadias in 5 and neurogenic bladder dysfunction in 1. Of the 40 patients with bladder exstrophy 8 had undergone ureterosigmoidostomy after failure of other types of urinary tract reconstruction (6 had upper tract dilatation before ureterosigmoidostomy). Three patients with previously damaged upper urinary tracts required early postoperative conversion because of severely increasing kidney dilatation. Three other patients required conversion after a mean of 10 years to preserve kidney function. One patient died after 16 years of a cause not related to ureterosigmoidostomy. The remaining 39 patients were alive with a functioning ureterosigmoidostomy after a mean followup of 14.7 years. The daytime continence rate was 97.4% (38 of 39 patients) and the complete continence rate was 92.3% (36 of 39). Except for 1 tubular adenoma that was removed successfully during routine colonoscopy, no bowel neoplasia has been observed. None of the 45 living patients has renal insufficiency. PMID- 2313805 TI - Single-stage feminization genitoplasty. AB - We present a modified technique for feminization genitoplasty, which combines the main features of the Hendren and Crawford pull-through operation and the Kogan reduction clitoroplasty. The unique features of the operation are the use of a flap of preputial skin to construct the vestibule and the anterior vaginal wall, and the universal use of the urogenital sinus to form the distal urethra, which avoids creation of female hypospadias. The new introitus is ample and, because there is no cut-back of the urogenital sinus, we avoid accidental incision of the urethral sphincter and the potential for urinary incontinence. There is no pull through of the vagina because the introitus is created by mobilization of anterior and posterior skin flaps. The clitoris and the neourethra are exteriorized through the folded preputial skin, which simulates the normal female anatomy. The cosmetic and functional results in 9 children who have undergone this procedure have been excellent. PMID- 2313806 TI - Neuroprostheses in the management of incontinence in myelomeningocele patients. AB - A 16-year-old boy and a 17-year-old girl underwent successful closure of the meningomyelocele defect in childhood but they continued to suffer incontinence of stool and urine. After a 5-day trial with percutaneous electrostimulation of the pudendal nerve both patients received permanent neuroprosthetic implants. They became completely continent of stool and exhibited greater than 90% improvement in urinary control. These patients demonstrate that there is a small subset of meningomyelocele patients who, despite absence of spontaneous reflex tonus in the urinary and bowel sphincters, nevertheless have preserved motor capabilities. PMID- 2313807 TI - Torsion of a spermatocele: a case report and review of the literature. AB - We report a case of torsion of a spermatocele in an adolescent. This condition has been described previously in adults. We recommend its consideration in the differential diagnosis of the acute scrotum in adolescents. PMID- 2313808 TI - On the importance of clinical trials. PMID- 2313809 TI - Ureteroscopic visualization of a cavernous hemangioma of the renal pelvis. AB - We describe a 54-year-old man in whom a capillary hemangioma of the renal pelvis was suspected ureteroscopically before excision. To our knowledge, this is the first case reported of this entity managed in this fashion. PMID- 2313810 TI - Aspirin-induced bilateral renal hemorrhage after extracorporeal shock wave lithotripsy therapy: implications and conclusions. AB - We report a case of bilateral intrarenal, subcapsular and perirenal hematomas after extracorporeal shock wave lithotripsy. Following treatment chest pain developed necessitating monitoring in the intensive care unit and cardiac evaluation. Serial hematocrit levels during the next 2 days revealed a decrease from 48 to 23%, requiring multiple transfusions. After therapy it was recognized that the patient had taken aspirin on a daily basis within 1 week before lithotripsy. We postulate that the aspirin ingestions acted as a potential predisposing factor in the formation of the bilateral renal hematoma. PMID- 2313811 TI - Chyluria treated with renal autotransplantation: a case report. AB - We report a rare case of chyluria in a patient from an area not endemic to filariasis. Initial surgical treatment consisted of stripping of the renal pedicle, following which the patient was free of symptoms for 3 months. Recurrence was noted and renal autotransplantation was performed. Chyluria has not recurred 12 months after the second operation. The etiology and various treatments of chyluria are discussed. PMID- 2313812 TI - Submucosal ureteral calculi: a new entity? AB - We describe 3 patients with ureteral calculi who failed multiple extracorporeal shock wave lithotripsy treatments and whose stones could not be visualized by ureteroscopy despite radiological confirmation. We contend that these ureteral stones migrated submucosally and are refractory to the aforementioned treatment modalities. Each patient had a common presenting complaint of intermittent flank pain 5 years in duration, leading us to believe that long-standing stone impaction is a prerequisite for this entity. Our experience is reviewed. PMID- 2313813 TI - Urothelial carcinoma occurring within an inverted papilloma of the ureter. AB - Only 5 cases of inverted papilloma of the ureter with a malignant component have been reported previously. We add case 6 to the literature. The incidence of concomitant malignancy in ureteral inverted papillomas is 3 times that found in similar lesions occurring in the bladder. PMID- 2313815 TI - An outlet obstruction caused by V-shaped bar at the bladder neck in a woman. AB - A case of outlet obstruction caused by a V-shaped bar at the bladder neck in a woman was treated successfully by transurethral resection of the bar. The poor urinary flow in our patient was believed to be due to impedance during voiding caused by retraction of the bladder neck in the anteroposterior direction by the bar. Our case is different from previously reported cases. PMID- 2313814 TI - Intravesical dimethyl sulfoxide instillations in the treatment of secondary amyloidosis of the bladder. AB - A-22-year-old woman with long-standing rheumatoid arthritis and secondary amyloidosis of the bladder had recurrent profuse macroscopic hematuria. She was treated with intravesical dimethyl sulfoxide instillation every 2 weeks for 1 year. She remained asymptomatic during the treatment and at 6 months. Progressive disappearance of amyloid from the superficial mucosa of the bladder was demonstrated in sequential histological examinations. PMID- 2313816 TI - Treatment of impotence with trazodone: a case report. AB - We describe a physician who successfully treated his own impotence for the last 4 years with trazodone, an antidepressant that may induce priapism. PMID- 2313817 TI - Brucella orchitis: a rare cause of testicular enlargement. AB - The differential diagnosis of the acutely enlarged testis includes numerous benign and malignant disease processes. Most are treated with radical orchiectomy due to difficulty in differentiating between these disorders preoperatively. Saving the involved testis, prevention of recurrent infectious disease in the opposite testis and prevention of systemic manifestations of testicular disease are but a few of the reasons for accurate diagnosis of the acute scrotum. We report a rare case of brucellosis presenting as an acute scrotal mass and stress the importance of accurately identifying the specific etiology of testicular pathology to prevent long-term morbidity. PMID- 2313818 TI - Solitary neurofibroma of scrotum. AB - We report a case of solitary neurofibroma of the scrotum. These tumors, which arise from perineural and Schwann cells, commonly occur throughout the body but they rarely have been reported to originate in the scrotum. No stigmata of von Recklinghausen's disease were identified. PMID- 2313819 TI - Postoperative spindle cell nodule of the prostate and bladder. AB - Postoperative spindle cell nodule of the prostate and bladder (a rare lesion often misinterpreted as sarcoma) is important to recognize. The nodule consists of a reactive proliferation of spindle cells occurring up to several months after a lower genitourinary tract procedure, such as transurethral resection or biopsy. We report on 5 patients with a spindle cell nodule after a prior operation on the prostate or bladder. Of these patients 2 initially were diagnosed as having leiomyosarcoma, including 1 who underwent radical cystoprostatectomy. Because of the potential for inappropriate treatment the clinician must be aware of this entity so that he might question the diagnosis and raise the possibility of a postoperative spindle cell nodule whenever sarcoma is diagnosed after recent surgical instrumentation for a nonmesenchymal lesion in the genitourinary tract. PMID- 2313820 TI - Effects of cromakalim (BRL 34915) and pinacidil on normal and hypertrophied rat detrusor in vitro. AB - Normal and hypertrophied rat detrusor were investigated in vitro with regard to effects of the K(+)-channel openers pinacidil and cromakalim. Both drugs abolished spontaneous contractile activity and induced a relaxation of normal and hypertrophied detrusor preparations. In both types of preparation, contractions elicited by K+, carbachol or electrical field stimulation were depressed in the presence of the K(+)-channel openers. Responses induced by K+ or electrical stimulation were more reduced in the hypertrophied than in the normal detrusor. Both K(+)-channel openers increased the efflux of 86Rb+ in a concentration dependent way and this increase was similar in normal and hypertrophied detrusor. If applicable to man, this data suggest that K(+)-channel openers may be effective in the treatment of bladder instability secondary to outflow obstruction. PMID- 2313821 TI - Effect of nifedipine on the contractile responses of the isolated rat bladder. AB - The effect of the calcium channel blocker nifedipine on the motor transmission in isolated preparations of rat detrusor smooth muscle has been studied. Nifedipine blocked the major part (75 to 80%) of the contractile response to electrical field stimulation, while atropine only blocked 20 to 25%. In preparations pretreated with atropine, the response to electrical field stimulation was completely abolished by nifedipine. The converse was also true; in preparations pretreated with nifedipine the response was fully blocked by atropine. The nifedipine-resistant response was greatly potentiated by the anticholinesterase eserine. The blocking action of nifedipine on motor transmission was partially antagonised by raising Ca2(+)-concentration. Acetylcholine concentration-response curve was shifted to the right by nifedipine. It is concluded that the non cholinergic motor neurotransmitter evokes contraction of the rat detrusor smooth muscle by activating external Ca2(+)-transport channels whereas the cholinergic contraction is mediated partly or wholly by alternative mechanisms. PMID- 2313822 TI - Transepithelial movement of non-polar and polar compounds in male rat reproductive tubule examined by in vivo microperifusion and in vivo micropuncture. AB - Proluminal movement of 3H-testosterone and 3H-sucrose from peritubular to intratubular fluids of the adult rat testis and epididymis was investigated by using in vivo microperifusion and subsequent micropuncture of seminiferous tubules and caput, corpus, and cauda epididymal tubules. Tubules were perifused with Minimum Essential Medium containing 3H-testosterone or 3H-sucrose. 14C polyethyleneglycol was included in the perifusion fluid as a marker for contamination of intraluminal fluid by interstitial fluid. Radioactivity of isotopes in perifusion and intraluminal fluids was determined at one and two hours after perifusion and the percentage of peritubular isotopes appearing in intraluminal fluid was determined. Net entry of 3H-sucrose into the seminiferous and epididymal tubules was significantly reduced. Proluminal movement of 3H androgen across the seminiferous epithelium was also restricted. In contrast, intraluminal 3H-androgen concentrations in caput epididymal fluid were 200 to 300% of those in peritubular fluid at both one and two hours after perifusion. Similar results were found in the corpus epididymidis. 3H-androgen concentrations in cauda epididymal fluid were approximately 125% of peritubular isotope concentrations. The exact mechanism underlying this uphill proluminal movement of 3H-androgen into the rat epididymal lumen remains to be elucidated. PMID- 2313823 TI - Effects of shielded or unshielded laser and electrohydraulic lithotripsy on rabbit bladder. AB - The pulsed dye laser and electrohydraulic lithotriptor (EHL) are both effective devices for fragmenting urinary and biliary calculi. Both fragment stones by producing a plasma-mediated shockwave. Recently, a plasma shield consisting of a hollow spring and a metal end cap has been described for use with the laser and EHL devices in an attempt to minimize tissue damage without adversely affecting stone fragmentation rates. The tissue effects produced by a pulsed dye laser and an EHL device with and without plasma shields were examined and compared using rabbit urinary bladders. If blood was present, the unshielded laser perforated the bladder wall in two pulses. However, in the absence of blood, over 100 pulses were needed for the laser to perforate the bladder. A mean of six pulses were required to perforate the bladder wall with a shielded laser. The unshielded EHL perforated the bladder wall in two pulses, whereas, the shielded EHL required a mean of 35 pulses. Microscopically, areas of exposure revealed hemorrhage and tissue ablation. We conclude that all devices examined can produce significant tissue damage when discharged directly onto bladder epithelium. PMID- 2313824 TI - AUA eighty-fifth annual meeting. American Urological Association, Inc. May 13-17, 1990, New Orleans. Abstracts. PMID- 2313825 TI - Confluent durable endothelialization of endarterectomized baboon aorta by early attachment of cultured endothelial cells. AB - Since surgical endarterectomy produces a highly thrombogenic vascular flow surface, we evaluated in baboons the capacity of acutely attached, unspread, cultured, homologous aortic endothelial cells to form durable, confluent endothelial cell monolayers and to interrupt acute thrombus formation during exposure to arterial blood flow conditions. When cultured baboon aortic endothelial cells were incubated with segments of freshly endarterectomized baboon aorta for 20 minutes in vitro, 3.8 x 10(5) endothelial cells/cm2 became attached. The endarterectomized surface treated with endothelial cells showed the presence of rounded, unspread endothelial cells with intervening bare areas of vascular media. Platelet deposition onto the endothelial cell--treated surface during exposure to blood under high flow conditions for 1 hour in vivo was markedly reduced by the attached but unspread endothelial cells. Moreover, these attached endothelial cells underwent spreading on the endarterectomized surface in the presence of high shear blood flow to form a confluent endothelial monolayer at the end of 1 hour. Thus acutely attached cultured endothelial cells form a durable thromboresistant monolayer on surgically denuded vascular surfaces during exposure to arterial blood flow. PMID- 2313826 TI - Reconstruction of the vena cava and of its primary tributaries: a preliminary report. AB - Encouraged by results from our research laboratory and from recent clinical reports, we performed reconstructions of the vena cava and/or its major tributaries on 16 patients (11 males and five females). Ages ranged from 8 to 81 years (median, 38 years). Eight patients had superior vena cava syndrome (benign, six; malignant, two). Two other patients had membranous occlusion of the inferior vena cava; four had iliocaval venous thrombosis; one had excision of the iliac veins for pelvic neurilemmoma; and one had inferior vena cava injury during orthotopic liver transplantation. The superior vena cava was reconstructed with spiral saphenous vein grafts in five patients and with expanded polytetrafluoroethylene in three. One spiral saphenous vein graft and one expanded polytetrafluoroethylene graft required revision; seven of the eight grafts were patent at follow-up, but one bifurcated spiral saphenous vein graft occluded at 3 months. The inferior vena cava and its tributaries were reconstructed with expanded polytetrafluoroethylene in five patients, spiral saphenous vein graft in two, and Dacron in one. At follow-up four of the expanded polytetrafluoroethylene grafts were patent. In contrast, one of the spiral saphenous vein grafts was occluded, and results of imaging studies of the other were inconclusive. Three of the five expanded polytetrafluoroethylene grafts had a concomitant temporary arteriovenous fistula at the groin; two had documented patency at follow-up. At the present time, spiral saphenous vein graft is our first choice for superior vena cava replacement. However, expanded polytetrafluoroethylene grafts are good alternatives and in the abdomen appear to perform better than spiral saphenous vein graft. These clinical results encourage us to perform further caval grafting in selected patients. PMID- 2313827 TI - Balloon embolectomy catheter-induced arterial injury: a comparison of four catheters. AB - This study compared four brands of balloon embolectomy catheters with respect to their mechanical characteristics and the histologic responses they elicit. Seventy-two 4F Becton-Dickinson, Edwards, Electro-Catheter, and Shiley catheters were studied. In vitro studies of penetration forces demonstrated that the forces required for arterial puncture were greatest for Shiley (295 +/- 22 gm) and least for Edwards catheter tips (217 +/- 11 gm) (p less than 0.05). This indicates that the Shiley catheter is least likely to puncture vessels in patients. Studies of balloon eccentricity showed that none of the balloons distended with excessive eccentricity. Studies of balloon emptying time demonstrated that the silicon Becton-Dickinson balloon required more than two times as long (5.7 +/- 1.2 seconds) as all other balloons to empty. Balloon emptying time reflects the ability of the surgeon to rapidly adapt the balloon to changing vessel diameter in patients. Shear forces were studied in cylindrical segments of arteries in vitro. Initial shear forces were significantly different among all catheters, Becton-Dickinson greater than Edwards greater than Shiley greater than Electro Catheter (p less than 0.05). In contrast, during catheter withdrawal dynamic shear forces were similar among the four brands of catheters. Balloon embolectomies were performed in vivo in the common carotid and common femoral arteries in 18 anesthetized dogs. Histologic examinations of the vessels exposed to 50, 100, and 200 gm shear forces showed that myointimal hyperplasia increased with rising shear forces for all catheters (p less than 0.05), but that there were no differences in the degree of myointimal hyperplasia elicited by the different brands of catheters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313828 TI - Phlebographic evaluation of nonthrombotic deep venous incompetence: new anatomic and functional aspects. AB - The anatomy, valvular function, and reflux patterns in the deep veins of the lower extremities were studied by ascending and descending phlebography in 126 limbs with nonthrombotic deep venous incompetence. The most common patterns were isolated reflux in the superficial femoral vein (51%), and combined reflux in the superficial femoral and the deep femoral veins (44%). Isolated deep femoral vein reflux occurred in 5%. As the degree of reflux in this vein varied considerably, a grading system for classification of deep femoral vein reflux was proposed. Depending on variations in the deep femoral vein anatomy, four different patterns could be distinguished. This study demonstrated that contrast filling of the deep femoral vein during ascending phlebography may indicate the presence of reflux in this vein. Complete visualization of the deep femoral vein is a new diagnostic sign that strongly correlates (p less than 0.001) with reflux in the deep femoral vein. The mean number of valves in the superficial femoral vein was reduced with increasing degree of reflux compared with a reference group consisting of 41 extremities without reflux. The diameter of the popliteal vein was significantly increased in the presence of pathologic reflux, which may indicate that vein wall dilation is a major cause of primary nonthrombotic deep venous incompetence. PMID- 2313829 TI - The resting interstitial tissue pressure in primary varicose veins. AB - In 31 patients with unilateral primary varicose veins the resting interstitial pressure in the deep posterior compartment of the leg was measured in three groups: I, asymptomatic; II, symptomatic; III, symptomatic with trophic changes. Spinal anesthesia was induced in all patients, and polytetrafluoroethylene (Teflon) catheters were inserted into the deep posterior compartment of both legs. The interstitial pressure was recorded with a bioelectronic strain-guage pressure monitor with the patient in the horizontal position with complete muscle relaxation. In control legs (n = 31) mean pressure was -2.48 mm Hg (range -5 to 1). However, the measurement in affected legs (n = 31) was significantly higher at 4.61 mm Hg (range 1 to 12). Results demonstrate the following: (1) Primary varicose veins (an exclusively epifascial abnormality) were consistently associated with an increased resting interstitial pressure of the subfascial tissues in the supramalleolar area of the leg. (b) The subfascial resting interstitial pressure was elevated in all stages of varicose veins, even those with short duration of the disease and with no symptoms at all. (c) In all three groups there was a significant increase in the subfascial interstitial pressure between the affected and contralateral extremity. In patients with trophic changes (group III) this increase was significantly higher than in the remaining groups, although there was no significant difference between the increased pressure of the remaining groups (groups I & II). PMID- 2313830 TI - Biochemical composition of human internal mammary artery and saphenous vein. AB - The long-term patency of the internal mammary artery graft is better than that of the saphenous vein graft in coronary bypass surgery because of a low incidence of atherosclerosis in the internal mammary artery. In search of a possible biochemical explanation of the low degree of atherosclerosis in the internal mammary artery we compared the chemical compositions of human internal mammary artery and saphenous vein obtained from 37 patients undergoing coronary bypass surgery. The levels of esterified cholesterol and free cholesterol were higher in the internal mammary artery than in the saphenous vein (p less than 0.001 and p less than 0.01, respectively), but lower than the levels reported in previous studies for coronary arteries. The amount of collagen was higher in the saphenous vein (p less than 0.001). Heparan sulfate was the major glycosaminoglycan fraction in the internal mammary artery, probably reflecting the higher cellularity and thicker media in the arterial rather than in the venous tissue. The level of dermatan sulfate was higher (p less than 0.001) in the saphenous vein than in the internal mammary artery. This difference is in a direction that could favor atherogenesis in the saphenous vein graft. PMID- 2313831 TI - Appraisal of cerebrospinal fluid alterations during aortic surgery with intrathecal papaverine administration and cerebrospinal fluid drainage. AB - We have previously described a technique for intrathecal administration of papaverine and cerebrospinal fluid drainage to prevent paraplegia after aortic surgery. Herein we report the cerebrospinal fluid and hemodynamic alterations that occurred in 11 patients who had 30 mg of a specially prepared papaverine hydrochloride 10% dextrose solution injected before aortic cross-clamping and also had cerebrospinal fluid drainage. A mean of 26.6 ml (SD +/- 7.1 ml) was drained before and 34.6 ml (SD +/- 24.1 ml) was drained during aortic cross clamping. The cerebrospinal fluid pressure increased significantly with anesthetic induction (p less than 0.03), during the period between anesthetic induction and cerebrospinal fluid drainage (p less than 0.005), and with aortic cross-clamping (p less than 0.05). These cerebrospinal fluid pressure alterations were similar to central venous pressure increases with a significant linear correlation between cerebral spinal fluid pressure and central venous pressure before anesthetic induction (r2 = 0.81, p less than 0.005), and both before (r2 = 0.94, p less than 0.005) and after (r2 = 0.74, p less than 0.005) aortic cross clamping. As expected, cerebrospinal fluid pressure was significantly reduced by cerebrospinal fluid drainage before aortic cross-clamping (p less than 0.001). The administration of intrathecal papaverine had no significant effect on mean arterial pressure, systemic vascular resistance, cerebrospinal fluid pressure, nor the pH of cerebrospinal fluid. Neither were there any complications noted related to the technique. All the patients survived, and no new immediate postoperative paraparesis or paraplegia occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313832 TI - Venous photoplethysmography: relationship between transducer position and regional distribution of venous insufficiency. AB - This study was performed to evaluate the photoplethysmographic technique in venous disease, especially regarding the effect of different positions of the photoplethysmographic transducer and the possibility of measuring regional changes in venous circulation. For this purpose photoplethysmographic recovery times were assessed from three different parts of the lower leg, that is, anterior midcalf level, medial midcalf level, and medial malleolar level. In patients with documented venous disease, regional photoplethysmographic findings were compared with results from venous pressure measurements, ascending/descending phlebography, foot volumetry, venous plethysmography, and Doppler investigation of the anterior tibial veins. The best correlation with pressure and volume recordings at the foot was obtained at the medial malleolar level. Only photoplethysmographic recovery times recorded at the anterior aspect of the leg were influenced by reflux in the anterior tibial veins. The present results indicate that photoplethysmographic recovery times reflect regional venous hemodynamics rather than overall venous hemodynamics in the limb. Photoplethysmographic recovery times were also found to be more related to superficial than to deep venous insufficiency. The results might have clinical implications when evaluating patients with regional venous dysfunction and in follow-up studies after venous surgery. PMID- 2313833 TI - Exogenous magnesium chloride-adenosine triphosphate administration during reperfusion reduces the extent of necrosis in previously ischemic skeletal muscle. AB - The lower extremity may be exposed to prolonged periods of ischemia, resulting in depletion of intracellular energy stores in the affected skeletal muscle. The role of adenine nucleotide reduction and failure of resynthesis on reperfusion in determining the extent of muscle necrosis was investigated in this study, in addition to the possible beneficial effects of the addition of exogenous adenosine triphosphate-magnesium chloride during early reperfusion. The isolated paired canine gracilis muscle model was used. After 4 hours of normothermic ischemia in group I, a perfusate Krebs-Henseleit solution plus the gradual reintroduction of oxygenated blood flow was compared to standard reperfusion. In group II, a similar infusion protocol was used, with the addition of 2 mmol/L adenosine triphosphate-magnesium chloride and compared to normal reperfusion. Adenosine triphosphate-magnesium chloride resulted in the salvage of skeletal muscle, 57% +/- 12% versus 44% +/- 14% (p less than 0.05, n = 6 pairs). Reperfusion with the solution alone increased the resulting necrosis (42% +/- 13% vs 60% +/- 20%, n = 6 pairs). Adenine nucleotide stores were not increased, but oxygen consumption was increased by magnesium chloride-adenosine triphosphate (p less than 0.05, analysis of variance [ANOVA]). A clear relationship was demonstrated between the fall in energy stores, as measured by a change in energy charge potential from preischemia to end ischemia levels, and the extent of resulting necrosis (p less than 0.01). In summary, the addition of 2 mmol/L to an infusion of Krebs-Henseleit solution during reperfusion results in significant salvage of skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313834 TI - Edema after femoropopliteal bypass surgery: lymphatic and venous theories of causation. AB - Edema of a lower extremity after femoropopliteal bypass surgery is a common problem. To study the causes of this phenomenon we evaluated 72 patients before and after surgery with noninvasive venous testing and venography. We also obtained postoperative lymphangiograms of a sample of 16 patients, eight with and eight without postoperative edema. Patients were sequentially assigned to one of four treatment groups: group A, a lymphatic-preserving inguinal dissection with conventional popliteal dissection; group B, a lymphatic-preserving popliteal dissection with conventional inguinal dissection; group C, lymphatic-preserving inguinal and popliteal dissections; group D, conventional inguinal and popliteal dissections. Twenty-nine (40%) of the 72 patients had postoperative edema. A similar proportion of patients with edema had deep venous thrombosis as patients without edema (3/29 [10%] vs 3/43 [7%], respectively). Patients in group D showed the highest incidence of edema, 17/20 or 85%, a rate significantly higher than the rates in the other three groups (p less than 0.001). Results of lymphangiograms were normal in six of the eight patients without edema (the other two had slight disruption), whereas they showed severe lymphatic disruption in all eight patients with edema. No association was found between edema and type of graft used or severity of preoperative symptoms. This study indicates that deep venous thrombosis is not an important cause of edema that occurs after bypass surgery and that intraoperative lymphatic disruption probably causes most cases of this complication. PMID- 2313836 TI - Description of the proximal anastomosis of axillobifemoral grafts: two case reports. PMID- 2313835 TI - Symptomatic abdominal aortic aneurysms in long-term survivors of cardiac transplantation. AB - Herein we report the only two long-term survivors of cardiac transplantation who underwent successful repair of symptomatic abdominal aortic aneurysms since the advent of cyclosporine therapy in 1983. Review of the world's literature indicates that the only two recorded cases of repair of symptomatic abdominal aortic aneurysms after cardiac transplantation occurred before the use of cyclosporine. The presentation and clinical course of our patients recently treated are presented, and perioperative care and immunosuppressive management are outlined. As the number of long-term survivors after cardiac transplantation increases, the incidence of other atherosclerotic complications including abdominal aortic aneurysm is likely to become more common, requiring extended cardiovascular follow-up. PMID- 2313837 TI - Above-knee amputation in patients with prior hip surgery: a caveat. PMID- 2313838 TI - Ways to assess test costs vary. PMID- 2313839 TI - It's important, but don't bank on exercise alone to prevent osteoporosis, experts say. PMID- 2313840 TI - New osteoporosis therapies appear closer. PMID- 2313842 TI - From the Centers for Disease Control. Prevalence of arthritic conditions--United States, 1987. PMID- 2313841 TI - From the National Institutes of Health. PMID- 2313843 TI - Screening for hematuria. PMID- 2313844 TI - Advance directive: do they provide direction? PMID- 2313845 TI - Long-term follow-up of health care workers with work-site exposure to human immunodeficiency virus. PMID- 2313846 TI - Animals in research: the American Medical Association's position. PMID- 2313847 TI - Skin cancer incidence: the effects of surveillance and migration. PMID- 2313848 TI - Excision of congenital nevi: immediate, complete, and in the office. PMID- 2313849 TI - Therapy for low high-density lipoprotein cholesterol in the face of 'desirable' levels of total cholesterol. PMID- 2313850 TI - Physician reporting of adverse drug reactions. Results of the Rhode Island Adverse Drug Reaction Reporting Project. AB - The Food and Drug Administration, Rockville, Md, contracted with the Rhode Island Department of Health, Providence, to conduct a project to increase reporting of suspected adverse drug reactions through physician education. Voluntary reporting, an important part of postmarketing surveillance that signals potential problems with marketed drugs, historically has been underused by physicians. After 2 years, there was a more than 17-fold increase in reports submitted directly from Rhode Island compared with the yearly average before initiation of the project. Increases in the total numbers of reports were paralleled by significant increases in the numbers of reports of severe reactions. Similar increases were not experienced nationally. Physicians in Rhode Island were surveyed before and 2 years after interventions began to determine changes in knowledge and attitudes about reporting of adverse drug reactions. Significant gains in knowledge and positive attitudes toward the reporting system occurred. We conclude that physicians can be stimulated to increase their reporting of suspected reactions, thereby improving the viability of the federal reporting system. PMID- 2313851 TI - Blood pressure changes following extracorporeal shock wave lithotripsy and other forms of treatment for nephrolithiasis. AB - Hypertension has been reported as a possible sequela of extracorporeal shock wave lithotripsy (ESWL). To evaluate this issue as well as the risk of hypertension following other current non-ESWL treatment options for urolithiasis (percutaneous nephrostolithotomy [PCNL], combined PCNL and ESWL, ureteroscopy, and spontaneous stone passage), detailed blood pressure measurements were made in 961 patients at least 1 year after treatment. All follow-up blood pressures were measured with random-zero blood pressure devices. This study includes 731 patients who received ESWL only (with an unmodified lithotriptor), 171 patients treated with ureteroscopy or spontaneous stone passage (control subjects), 25 patients who received PCNL only, and 34 patients treated with both ESWL and PCNL. In patients who received ESWL only, the annualized incidence of hypertension (2.4%) did not differ significantly from that in control patients (4.0%). Among patients who received ESWL, no correlation was found between the incidence of hypertension and unilateral vs bilateral treatments, the number of shock waves administered, the kilovoltage applied, or the power (number of shock waves times kilovoltage). However, there was a significant rise in diastolic blood pressure after treatment with ESWL (0.78 mm Hg), but not in the control group (-0.88 mm Hg). The long-term significance of this change in diastolic blood pressure following ESWL is unknown and requires further study. PMID- 2313852 TI - Systemic lupus erythematosus. Treatment-related complications superimposed on chronic disease. PMID- 2313853 TI - Reporting drug side effects: signals and noise. PMID- 2313854 TI - A piece of my mind. Keeper of the gate. PMID- 2313855 TI - Clinical decision making: from theory to practice. Practice policies--guidelines for methods. PMID- 2313856 TI - Nurses oppose registered care technician recruitment. PMID- 2313857 TI - Registered care technicians can ease nurses' tasks. PMID- 2313858 TI - Prescribing psychologists: a positive step. PMID- 2313859 TI - Knowing what you don't know. PMID- 2313860 TI - Resident opportunities at the newest US PHS agency. PMID- 2313861 TI - Trying to consider cancer therapy alternatives, assessors of technology appear to come up short. PMID- 2313862 TI - From the Food and Drug Administration. PMID- 2313863 TI - From the Centers for Disease Control. Low birthweight--United States, 1975-1987. PMID- 2313864 TI - Injury coding and hospital discharge data. PMID- 2313865 TI - Trauma registries and organ transplantation. PMID- 2313866 TI - The effect of the 65-mph speed limit on fatalities in New Mexico. PMID- 2313867 TI - Prenatal choice. PMID- 2313869 TI - A piece of my mind. Another Saturday. PMID- 2313868 TI - Mandatory premarital HIV testing: the Illinois experience. PMID- 2313870 TI - Association between vaginal douching and acute pelvic inflammatory disease. AB - The vaginal douching habits of 100 consecutive municipal hospital patients with verified pelvic inflammatory disease (cases) were compared with those of 762 randomly selected controls (random controls) and 119 women thought to have pelvic inflammatory disease but in whom the diagnosis was not confirmed by laparoscopy and/or endometrial biopsy specimen (internal controls). Because patients had been symptomatic for no more than 3 weeks, current douching was arbitrarily defined as any douching during the previous 2 months. Current douching was more common among those with pelvic inflammatory disease than among random controls or internal controls. Among current douchers, pelvic inflammatory disease was significantly related to frequency of douching. For example, when cases were compared with random controls, those who douched three or more times per month were 3.6 times more likely than those who douched less than once per month to have confirmed pelvic inflammatory disease. A logistic regression model was used to adjust for demographic, behavioral, and other possible confounding variables. Even after adjustments, douching during the previous 2 months remained associated with pelvic inflammatory disease. These data suggest that among these women vaginal douching may be a risk factor for pelvic inflammatory disease. PMID- 2313872 TI - Postponement of death until symbolically meaningful occasions. AB - This study shows that mortality dips before a symbolically meaningful occasion and peaks just afterward. Mortality among Chinese (n = 1288) dips by 35.1% in the week before the Harvest Moon Festival and peaks by the same amount (34.6%) in the week after. We chose to study mortality among Chinese and a Chinese holiday for two reasons. First, the holiday moves around the calendar, thus allowing separation of the effects of the holiday from fixed, monthly mortality effects. Second, the holiday appeals strongly to one (experimental) group and not to others (which can be used as control groups). In terms of percentage, cerebrovascular diseases displayed the largest dip/peak pattern, followed by diseases of the heart, and then malignant neoplasms. The dip/peak mortality pattern does not appear in various non-Chinese control groups. The statistical significance of the findings was demonstrated with linear and curvilinear regression analysis and with two nonparametric tests. After testing alternative explanations for the findings, we concluded that the dip/peak pattern occurs because death can be briefly postponed until after the occurrence of a significant occasion. PMID- 2313871 TI - The effect of preexisting conditions on mortality in trauma patients. AB - A case-control design was used to investigate the effects of preexisting chronic conditions on in-hospital mortality in adult trauma patients. Cases consisted of all trauma deaths (n = 3074) that occurred in 1983 in any of the 331 acute care hospitals in California. Three to four control patients (injured survivors) were matched to each case patient on the basis of injury severity, age, and individual hospital (n = 9869). The data source consisted of hospital discharge abstract data uniformly collected on all admissions to acute care hospitals in the state. Conditional logistic regression techniques were used to estimate the relative odds of dying for patients with and without one or more of 11 preexisting chronic conditions identified as potentially detrimental to outcome. The presence of cirrhosis (relative odds = 4.5), congenital coagulopathy (relative odds = 3.2), ischemic heart disease (relative odds = 1.8), chronic obstructive pulmonary disease (relative odds = 1.8), and diabetes (relative odds = 1.2) all significantly increased the risk of dying. These data provide statistical evidence to support the recommendation of the American College of Surgeons that the presence of underlying disease be considered in decisions to triage and transfer patients to trauma centers. They also underscore the importance of underlying disease in the case-mix adjustment of case-fatality rates and the identification of unexpected deaths for quality assurance review. PMID- 2313873 TI - Accidental toddler drowning in 5-gallon buckets. AB - We have identified a previously unrecognized source of accidental drowning in infants and toddlers: 5-gal (19-L) industrial buckets. Twelve cases of drownings in these large-capacity buckets constituted 24% of all infant and toddler (age less than 3 years) drownings investigated by the Cook County (Illinois) Medical Examiner's Office from January 1985 to June 1989. The buckets, all with 5-gal and 18-kg capacity, are constructed of heavy, rigid plastic and are intended for industrial use. Home use, typically as mop buckets, was associated with the toddlers' death. The large size and heavy construction of these buckets as well as the toddlers' cephalad center of gravity and undeveloped coordination prohibit the toddlers from extricating themselves after peering into and falling inside the buckets. Parents and public health officials should be advised that domestic use of these containers poses a serious threat to the safety of curious toddlers. Adults should never leave toddlers unattended around even small amounts of water. PMID- 2313874 TI - The role of the brain in physical disease. Folklore, normal science, or paradigm shift? PMID- 2313875 TI - AIDS policy into the 1990s. PMID- 2313876 TI - From the Office of the General Counsel. When health care payers have market power. PMID- 2313877 TI - [A large scale cohort study on the effect of life styles on the risk of cancer by each site]. AB - 265,118 (m; 12226, f; 142857) adults aged 40 and above were followed up for 17 years (1966-1982) and age standardized mortality rates for cancer of each site were analysed by life style variables. The study revealed smoking cessation and increased consumption of green-yellow vegetables as the most effective common way of primary prevention (e.g. cancers of lung, stomach, cervix) followed by moderation in drinking of alcohols (e.g. cancers of mouth, pharynx, esophagus, sigmoid colon) and avoidance of excess consumption of animal fat (e.g. cancer of pancreas, breast). To reduce chances of exposure to passive smoking was also considered important for selected sites (e.g. cancers of lung, nasal sinus, breast, brain tumor and leukemia). PMID- 2313878 TI - [Studies on evaluation of risk factors of cancer by a large-scale cohort study newly organized in Japan--planning and pilot study]. AB - A large-scale cohort study has been planned in cooperation of 22 epidemiologists in Japan since 1986. The objective of this new cohort aged more than 40, consisting the inhabitants throughout Japan is to evaluate risk factors of cancer already known and suspected agents in so rapidly changing society of Japan where age-sex contraction of population, disease pattern and lifestyle habits have remarkably changing for the last decades. The factors examined are not only social factors but also biological ones from blood, serum and other body fluids. At the same time serum bank of healthy inhabitants in Japan is established in this study. PMID- 2313879 TI - [Liver cancer and life style--drinking habits and smoking habits]. AB - Japan is one of the endemic area of liver cancer in the world with its incidence rate of more than 30 per 100,000 population for males in Osaka. It is well known that Hepatitis B virus is closely related with hepatocellular carcinoma, however, its prevalence is moderately high (2-3%) in Japan. The relationship between drinking and liver cancer is examined by 3 different type of studies. First, more than 13,000 male alcoholics were followed for 9.9 years in average. Their incidence rate of liver cancer was 1.4 times higher than that of general population. Second, the case-control study of liver cancer among HBs antigen positives revealed that drinking habit was related with liver cancer even after adjusted with smoking habits. Lastly hospital based case-control study also showed the positive relationship between drinking habit and liver cancer. The relationship between smoking and liver cancer is still unclear. PMID- 2313880 TI - [A review of gastric cancer and life style]. AB - Descriptive epidemiology of gastric cancer reveals remarkable decline in incidence and mortality rates in recent years in many countries of the world and suggests important roles of dietary factors in its etiology. Cigarette smoking appears one of the risk factors. Case-control and cohort studies, on the whole, show risk increase associated with intake of high salt foods (salted fish and pickles) and risk decrease associated with the consumption of fresh fruits and vegetables. These associations are, in part, supported by experimental studies. Further evidence should be sought by improving the methods in assessing dietary intake. PMID- 2313881 TI - [Life-style and cancer prevention. Activities of the Department of Cancer Prevention, Osaka Cancer Prevention and Detection Center]. AB - The role of the Department of Cancer Prevention, Osaka Cancer Prevention and Detection Center which was established in 1987 is to conduct practical research works in the area of primary prevention of cancer through life-style modification. We have so far examined the applicability and efficacy of such tools as population-based smoking cessation contest, nicotine gum, health risk appraisal and "Know Your Body" program. The outline of our activities and future plans are introduced. PMID- 2313882 TI - [Stomach cancer mortality and nutrition intake in northern Japan--especially on relation to sodium chloride]. AB - There is a big difference on the stomach cancer (SC) mortality between the north western and the north-eastern parts of Honshu (mainland of Japan) although not much differences on cerebrovascular disease (CVD) mortality can be observed between these two areas while both of these diseases are said to be related to high-salted diets. The relation between diet and age-adjusted mortality of SC and CVD in northern Honshu was examined here, based on the results of the nutrition survey carried out by prefecture office (1971-87, 6 prefectures, total of 18 data sets). The results are summarized as follows: 1. There are no significant differences on salt intake between the north-western and the north-eastern parts of Honshu. 2. Intake of milk and dairy products is negatively related to SC. 3. Intake of animal protein is negatively related to CVD. PMID- 2313883 TI - [Stomach cancer mortality and life styles in Niigata Prefecture]. AB - Niigata prefecture is featured by the extremely high mortality of stomach cancer ranking first in men and 6th in women among 47 prefectures in Japan. It is also featured by the highest consumption of rice. Daily salt consumption in Niigata is also higher by 2 grams than country average and by 5.8 grams than Okinawa, the area with the lowest stomach cancer mortality. The amount of consumption of rice and salt was observed significantly higher in households with 2 or more stomach cancer cases than the households with no case of stomach cancer among all food items studied. The stomach cancer mortality rates by health center districts were significantly associated with their salt/rice ratio, suggesting excess consumption of salt is the major risk factor of the disease rather than rice itself. PMID- 2313884 TI - [Lipid peroxidation as a biological marker of mucosal changes in the stomach]. AB - Dose-related increase of malondialdehyde (MDA) was found in both gastric mucosa and urine after 5-week administration of 4.0, 2.0, 1.0, 0.5, 0.25 or 0% NaCl supplemented diet to rats. NaCl, a gastric tumor promoter, is associated with enhanced lipid peroxidation in the gastric mucosa. The urinary MDA level was found to be a good indicator of lipid peroxidation state in the gastric mucosa, higher levels of MDA in the urine clearly correlating with data for stomach glandular tissue. In man, elevation of MDA was also observed in the urine of patients with gastric lesions such as chronic gastritis, precancerous and cancer, as well as in individuals suffering from liver and kidney disease. PMID- 2313885 TI - [The effect of smoking and drinking habit on the process from liver cirrhosis to liver cancer]. AB - A retrospective cohort study of liver cirrhosis cases was carried out. 270 cases of liver cirrhosis which were confirmed histologically from 1972 to 1981 at Juntendo University Hospital, were followed up until the end of 1988. The average observation period for these cases was 74 months or 6.2 years, and we found 141 death cases including 46 of primary liver cancer (PLC). The analysis of survival rate revealed that the smoking group had a slightly higher death rate of PLC than non-smokers, and the ex-smoker group had a much higher survival rate than the continuous smoking group. On the other hand, it was found that the alcohol drinking group had a much lower death rate of PLC than the non-drinkers group, and that there was no difference of the survival rate among drinkers, non drinkers and ex-drinkers. PMID- 2313886 TI - [Estimation of the long-term risks of death from smoking--application to public health education]. AB - We calculated the long-term risks of death from smoking-related diseases for individuals of various smoking status using the health risk appraisal system based on Japanese epidemiologic and statistic data. For a 35-year-old man who had started to smoke at age 20 and smoked 20 cigarettes per day, the estimated probability of dying of lung cancer before reaching age 85 was 7.1 per cent, and 6.7, 7.3, 14.2 per cent for stomach cancer, coronary heart disease, and cerebrovascular disease respectively. If this same person had smoked 40 cigarettes per day, the corresponding probabilities were 9.4, 7.0, 14.3, 16.5 per cent respectively. If this same 35 year old man had never smoked, the probability of dying of lung cancer before age 85 was only 0.8 per cent and 5.0, 3.8, 12.5 per cent for the other smoking-related diseases. If this same person had started to smoke at age 20 and stopped smoking at the age of 35 or 55, the corresponding probabilities were nearly the same as those for a nonsmoker. PMID- 2313887 TI - [Association of indoor air pollution and passive smoking with lung cancer in Osaka, Japan]. AB - A hospital-based case-control study was conducted at 8 hospitals in Osaka in order to clarify risk factors among non-smoking women. A total of 129 lung cancer cases and 519 controls were investigated. An elevated risk was observed for women who had used wood or straw as cooking fuels at 30 years of age. Maternal smoking in childhood also seemed to raise the risk. No elevated risks were observed for husband smoking and use of heating apparatus so far. PMID- 2313888 TI - [An epidemiological study on relationship between life style and colorectal cancer]. AB - In Kumamoto prefecture, 2,359 cases were diagnosed as colorectal cancer and operated in 5 years from 1983 to 1987. Their records were analysed to determine the annual incidences in the cecum, ascending, transverse, descending, sigmoid colon and rectum. The female age-adjusted mortality from cancer of the cecum and ascending colon was slightly surpassed that of the male's. While the incidences of colonic and rectal cancer were 21.0 per 100,000 in 1983, they have increased to 26.0 per 100,000 in 1987. As for the crude mortality, it was 11.5 per 100,000 in 1983 and 13.5 per 100,000 in 1987 respectively. Increasing of the incidence was greatest in people over 50 years of age. PMID- 2313889 TI - [A case control study of cancer of the pancreas]. AB - We report the findings of a case-control study of cancer of the pancreas, which was conducted in Hokkaido Prefecture. Seventy-one patients with pancreatic cancer were matched on sex and age (+/- 3 years) to 142 community-based controls. The latter had telephone interviews. We questioned all subjects about demographic factors, diet, beverage consumption, and medical and surgical history. Significantly decreased risks were associated with consumption of raw vegetables and green tea. The risk increased significantly with consumption of the fat of meat, boiled fish, coffee, black tea and alcoholic beverages. PMID- 2313890 TI - [Hospital epidemiology--a comparative case control study of breast and cervical cancers]. AB - To promote the comprehensive measure of cancer prevention for future, a hospital based epidemiological study on a large scale has started at the Aichi Cancer Center Hospital. As the first step of this study by using a common questionnaire, a simultaneous case-control study on the two cancers involving 175 cases with breast cancer, 56 cases with cervical cancer and 231 controls was conducted in 1988. Body weight was positively related to breast cancer only in older (50-69) patients. Young age at first birth (less than or equal to 23) increased the risk of cervical cancer (OR = 4.1). Active and passive smoking increased the risk of cervical cancer (OR = 2.6, 2.3) but only passive smoking increased the risk of older breast cancer (OR = 2.0). Frequent intakes of green vegetables and carrot decreased the risk of younger (30-49) breast cancer (OR = 0.5, 0.5) and cervical cancer (OR = 0.3, 0.5). Some other factors with positive and negative effects on these two cancers were identified in this case-control analysis. PMID- 2313892 TI - [A study of environmental factors before and during pregnancy in childhood malignancy]. AB - To determine risk factors in childhood malignancy, we compared parental and fetal exposure rates of some environmental factors among major children's malignancies based on 2722 cases of the Japan Children's Cancer Registry Database. The rates of parental exposure to irradiation, chemicals, and maternal dosage before and during pregnancies and of maternal smoking and drinking habit during pregnancies were slightly but statistically significantly high in some blastomas in which loss of heterozygosity of the genes has been reported. On the other hand, there were no significant correlations with these factors in leukemia and malignant lymphoma, which have been reported to be related to special chromosomal translocations. These possible risk factors should be examined by experimental and more detailed epidemiological studies. PMID- 2313891 TI - [A case control study of breast cancer, mammary cyst and dietary, drinking or smoking habit in Japan]. AB - A matched pair analysis was done among patients with breast cancer, those with mammary cyst and those without any abnormality in mammary gland by ultrasonic echogram (U.S.) to investigate the relationship between dietary or smoking habit and mammary disease. Breast cancer was diagnosed pathologically, and mammary cyst by U.S.. 49 cancer-normal pairs and 36 cyst-normal pairs were obtained. Breast cancer had significant relationships with a large intake of bread (risk ratio (RR) = 1.60, 95% confidence interval (CI) = 1.03-2.49), margarine (RR = 2.17, CI = 1.20-3.49), cakes (RR = 1.83, CI = 1.18-2.84), soft drinks with sugar (RR = 8.00, CI = 1.33-48.29), meat (RR = 1.48, CI = 1.04-2.10) and a small intake of alcohol (RR = 0.20, CI = 0.06-0.63). Mammary cyst was significantly related with a large intake of fat (RR = 1.56, CI = 1.02-2.38). The result indicates that in Japan women with westernized dietary habit have a larger risk of breast cancer. PMID- 2313893 TI - [Familial history of cancer and dietary pattern, serum cholesterol, serum protein and blood hemoglobin]. AB - The relationships between the history of cancer in parents and the dietary pattern, serum cholesterol, serum protein and blood hemoglobin were examined to assess the possible role of lifestyle transmission in the familial aggregation of cancer. Individuals with history of cancer in parents were selected from a population of 1,221 individuals. Five age- and sex-matched controls for each case were selected from individuals, the parents of whom were alive at the age of the case parent. Intake of miso soup, pickles and milk product showed associations with the history of cancer in parents. It was also found that serum cholesterol was significantly lower in individuals with history of cancer other than stomach in the mother. Interestingly, serum protein, especially the globulin fraction, was found to be significantly lower among individuals with the history of cancer in parents. These findings suggest that lifestyle transmission might play some role in the familial aggregation of cancer. PMID- 2313894 TI - [The relation among the life style and the clinical laboratory data]. AB - The concept of risk pattern is introduced as the new point of view for the cancer prevention. The risk pattern should be got by drawing out the feature of the human information composed of dietary habit, life style, family history, laboratory data. Using the large scale health screening data in Nagano (total population = 93, 403, 1,140 byte/person), the risk pattern is analysed and the relation among the variables are discussed. PMID- 2313895 TI - [A case-control study of psychosocial stress and cancer]. AB - As psychosocial stress has been suspected as a risk factor for cancer, a case control study was conducted. A total 106 cases with cancer of the various sites and 106 age-sex matched hospital control with non-cancerous disease or without disease were compared on their responses to the questionnaire which included the items on life event, stress coping behavior, emotional support, and neuroticism. No significant odds ratio was observed for each dimension of the stress and the comprehensive stress index, even after adjusting for smoking and other life style factors. Some methodological problems were discussed. PMID- 2313896 TI - [The use of information theory in the evaluation of cancer control]. AB - The age-adjusted incidence/mortality rate has been used as an index for the decrease in cancer deaths due to the first and second prevention. This index is popular in the fields of Epidemiology and Health Statistics, but does not represent the increase in cancer deaths among the elderly and the variation among the rates of primary cancer in each organ. If preventive activities have contributed to cancer control, the age distribution of the incidence/mortality of cancer patients should be skewed to old age, and the rates at high-risk cancer sites should be decreased. To evaluate the results of attempts at cancer prevention, a new index called "entropy" was produced using Information Theory. The "entropy" index of the age distribution of deaths from cancer, when calculated by Brillouin's formula, decreased chronologically and the "entropy" index of the site distribution increases. These results indicates that recent cancer control has been effective. In conclusion, this new index "entropy" seems quite useful in evaluating the effects of cancer control. PMID- 2313897 TI - [A dietary method for epidemiological study of cancer]. AB - A semiquantitative frequency questionnaire was developed to estimate the average intake of foods and nutrients of individuals with the aim of utilization in cancer epidemiology. Validity of the questionnaire was evaluated in comparison with four 7-day dietary records carried on 25 spouses over one year. Absolute mean intakes estimated by the questionnaire and by the records were roughly comparable at the group level. However, the individual's estimated intakes generally showed poor agreements between the two methods in terms of rank correlation, except for a few foods such as fish and milk and for alcoholic beverages. Further efforts should be exercised to develop a more accurate dietary method. PMID- 2313898 TI - [A follow-up study of the elderly in agricultural and piscatorial areas of Hokkaido]. AB - A base-line survey was performed for 3,185 persons over 40 years of age in 1984 and 1985 in agricultural and piscatorial areas of Hokkaido with regards to their dietary habits and life style. Of them, 147 persons died prior to the recent follow-up survey of 1988. As a result of a case-control study of the dead with those of the followed-up group, a more frequent intake of instant noodles was indicated as significantly increasing the risk of death, even after adjusting for the health status at the base-line survey and other confounding variables (the adjusted relative risk = 1.44 per a frequency class, p = 0.049). PMID- 2313899 TI - [Ecological study on cancer mortality and lifestyle in Japan]. AB - Cancer mortality varies even in the uni-racial population of Japan. Age-adjusted mortality rate of stomach cancer in the highest prefecture is almost three times higher than the lowest. A cross-sectional study in five populations in Japan is being conducted in order to clarify the relationship between cancer mortality and lifestyle risk factors using some biochemical markers, i.e. nutrients (vitamins, trace minerals, lipids), hormones, etc. Each area has approximately population 100,000 and a total of 170 randomly selected males aged 40 to 49 are included. Wives of selected men are also included. Blood and urine sampling will also be done, with an interview and medical examination. Survey in Iwate and Okinawa prefectures has been completed in 1990 which will be extended to Nagano and Akita prefectures in 1990 and Tokyo metropolitan in 1991. PMID- 2313900 TI - [Polycythemia vera terminating in myelodysplastic syndrome]. AB - A 77-year-old male, who had been treated with carboquone and busulfan for polycythemia vera (PV), developed myelodysplastic syndrome (MDS) 8 years later. On admission the peripheral blood revealed pancytopenia, but blastoid cells were not noted. The bone marrow showed hypercellularity, and functional and morphological abnormalities in trilineages of hemocytes. Cytogenetic study showed complex abnormalities involving chromosomes 5 and 7. We diagnosed this case as secondary MDS to alkylating agents. He was treated with 1, 25 (OH)2 vitamin D3. However, it was not effective and the percentage of myeloblasts increased to 14.4%. In spite of supportive therapy, he died of sepsis due to urinary tract infection. PMID- 2313901 TI - [Myelodysplastic syndrome with complex chromosome abnormalities and peculiar fibril formation in granulocytes]. AB - We report a case of myelodysplastic syndrome with peculiar fibril formation in granulocytes shown through electron microscope and complex karyotypic abnormalities including ring chromosomes. The patient, a 76-year-old male, was consulted for mild pancytopenia in February 1987. After 5 month, his hematological findings showed severe pancytopenia getting worse rapidly and presence of blasts in the peripheral blood. He had slightly hypercellular marrow with marked trilineage dysplasia and increased number of blasts (12.6%). Chromosome analysis from the bone marrow cells revealed its various structural abnormalities, especially in No. 3, 4, 5, 7, 11 with translocation on 11q11, and large ring chromosomes derived from unknown one. By electron microscopic study, we observed bizarre structures, which was peculiar fibril formation as bundles of filament resembling actin paracrystals, throughout cytoplasm as well as within nucleus in granulocytes. PMID- 2313902 TI - [Peculiar increase of plasma plasminogen activator inhibitor 1 levels in patients with hemophagocytic histiocytosis]. AB - There was a markedly significant increase of plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor 1 (PAI-1) and PAI activity in 3 patients with hemophagocytic histiocytosis (HPH) as compared with DIC patients with multi-organ failure (MOF). Of particular interest was the peculiar increase of PAI-1 levels, that is, the average PAI-1 level was 2,673 ng/ml, while that in DIC patients with MOF was 66 ng/ml. We conclude that the striking increase of plasma PAI-1 levels may be a pathognomonic feature of HPH and may contribute to the pathogenesis of DIC and/or MOF associated with HPH. PMID- 2313903 TI - [Bleeding time and volume in vitro by THROMBOSTAT]. AB - We tested an in vitro system simulating bleeding time reported by Kratzer et al. Primary hemostasis was studied perfusing an artificial vessel with citrated blood under a constant pressure of 40 mmHg, measuring the blood volume perfused (bleeding volume) and the time until blood flow stopped (bleeding time). The artificial vessel consists of a glass capillary simulating arteriole and a filter covered with collagen type I to provide a surface for the adhesion of platelets. The bleeding volume (mean +/- SD microliters) was 317.7 +/- 93.8 in controls (n = 19), 487.3 +/- 242.1 in idiopathic thrombocytopenic purpura (n = 9), 666.8 +/- 224.1 in aplastic anemia and paroxysmal nocturnal hemoglobinuria (n = 4), greater than 820 in von Willebrand's disease (n = 3), 231.0 +/- 74.5 in hemophilia A (n = 3), 499.0 +/- 269.4 in liver cirrhosis (n = 6), and 457.7 +/- 229.0 in myeloproliferative disorders (n = 11). When citrated blood was applied to this system after incubation with monoclonal antibodies (MoAb) to von Willebrand factor or platelet membrane glycoprotein Ib (GPIb), bleeding volume was significantly increased while no effects were observed after incubation with MoAb to GPIIb/IIIa, factor VIII: CAg and factor XIIIa. These data suggest that in vitro model of primary hemostasis could be used for not only diagnosing bleeding disorders although 'time' is not reliable, but also investigating the mechanisms of hemostasis. PMID- 2313904 TI - [Chronic myelogenous leukemia with marked thrombocytosis--comparison with essential thrombocythemia with Ph1 in its megakaryokinetics]. AB - A case of chronic myelogenous leukemia (CML) with marked thrombocytosis and its megakaryokinetics were reported. Patient was 57-year old woman who had a marked thrombocytosis (1,413 x 10(3)/microliters) and a bone marrow megakaryocytosis. Bone marrow karyotype demonstrated Ph1 chromosome in all cells examined. However, on physical examination, there was no splenomegaly. CBC showed no immature myeloid cells, and neutrophil alkaline phosphatase was elevated. These manifestations were consistent with so called essential thrombocythemia (ET) with Ph1 chromosome reported by Nissenblatt. To know the megakaryokinetics of this case, we examined the number of colony forming unit-megakaryocyte (CFU-M), platelet glycoprotein (PGP) IIb/IIIa positive cells, cytoplasmic area, and DNA content, comparing with those of normal subjects, CML, and ET. We found a marked increase of CFU-M and PGP IIb/IIIa positive cells, but in contrast, decreased DNA content and cytoplasmic area. This pattern of megakaryokinetics was consistent with that of CML. We conclude that ET with Ph1 chromosome may be a variant of CML rather than ET itself. PMID- 2313905 TI - [Long survival of a patient presented with blastic crisis of chronic myelomonocytic leukemia]. AB - A 77-year-old man was diagnosed as having acute myelomonocytic leukemia (M4) with increased ringed sideroblasts in the bone marrow (BM) in October, 1979. Complete remission was achieved and ringed sideroblasts disappeared after two courses of CMP (cytarabine, 6-mercaptopurine, prednisolone) therapy. Following remission, there was no increase of blasts during the course of the disease, but monocytosis and dysmyelopoiesis persisted for about seven years. The monocytosis was controlled by 6-mercaptopurine. In June, 1986, however, monocytosis in peripheral blood (PB) and BM developed again, and there was severe pancytopenia and reappearance of ringed sideroblasts without increase of blasts. The patient died of pneumonia on September, 1986. Postmortem examination revealed hypercellular marrow with a few blasts, leukemic cell infiltration into spleen, liver and lymph nodes, ad lung cancer. His clinical and hematological features after remission of acute leukemia accorded with those of CMMoL. The dysmyelopoiesis observed in this case in not induced by anti-leukemic agents, but originated from the same clone as the initial AMMoL, and his disease was thought to be CMMoL converted from blastic crisis to chronic phase. PMID- 2313906 TI - [Effect of splenectomy for management of thrombocytopenia associated with systemic lupus erythematosus: a case report]. AB - A 51-year-old female with systemic lupus erythematosus (SLE) was admitted in November 1987 because of general fatigue and muscular weakness. She was treated with prednisolone (PSL) 30 mg and azathioprine (AZP) 50 mg after failure in the management of thrombocytopenia by PSL 15 mg. She exhibited no splenomegaly. Muscular atrophy and weakness were seen in the proximal muscles. Her platelet count was 44,000/microliters. A bone marrow aspiration revealed an increase in megakaryocytes. The blood chemistry revealed a normal CPK level and an elevated LDH level, indicating a presence of steroid myopathy. A splenectomy was performed after an increase of platelet count by giving gamma-globulin 400 mg/kg for 5 days. The platelet count rose to 368,000/microliters on the 46th postoperative day. She was treated with PSL 5 mg and AZP 50 mg as postsplenectomy therapy. The splenectomy did not adversely affect other aspects of SLE, in particular, renal function. She had no major complications in the postoperative period. Her platelet count reached a plateau 4 months later and revealed 115,000/microliters 18 months postoperatively. PMID- 2313907 TI - [Bestatin-induced intravascular hemolysis in a patient with acute myelocytic leukemia]. AB - We encountered a patient who developed intravascular hemolysis while being treated with immunotherapy of bestatin. A 18-year-old female, diagnosed as having acute myelocytic leukemia and remained in complete remission for about 18 months by repeated consolidation therapy, was admitted to our hospital because of sudden fall of Hb concentration. Nine days prior to admission, bestatin, 30 mg daily, was resumed following a rest period of 2 weeks. Bestatin was started after the first complete remission had been achieved, Urine was dark brown with positive occult blood, but no red cells were observed. Hb was 7.9 g/dl, the number of reticulocytes 14.1%, WBC 3100/microliters with a normal classification, and platelets 6.1 x 10(4)/microliters. The serum total bilirubin was 2.3 mg/dl with a direct component of 0.8 mg/dl. Serum LDH was markedly elevated. Serum Hb was 0.12 g/dl and haptoglobin was less than 10 mg/dl. Direct and indirect Coombs' tests were both negative. Lymphocyte stimulation test by bestatin was positive. Full recovery followed the cessation of bestatin therapy and the initiation of corticosteroid therapy. It may be speculated from our case that discontinuous administration of bestatin may have been an opportune setting for developing a side effect of severe intravascular hemolysis. PMID- 2313908 TI - [Acute leukemia with active hemophagocytosis, positive immunologic markers for the megakaryocyte-platelet lineage, and translocation (16; 21) (p11; q22]. AB - We report a case of infantile acute leukemia with t(16; 21) (p11; q22). The patient was a phenotypically normal one-year-old girl without lymphadenopathy or hepatosplenomegaly. Her peripheral blood at diagnosis showed anemia, thrombocytopenia, and many circulating blasts. Bone marrow blasts were monocytoid with fine reticular nuclear chromatin, abundant grayish-blue cytoplasm with occasional pseudopods or cytoplasmic projections and active hemophagocytosis. Serum levels of lysozyme and ferritin were normal. These blasts were not stained with butyrate esterase and immunologic study showed KOR-P77+ (anti-megakaryocyte monoclonal antibody), MY9+, Ia-. Electron microscopic examination failed to show platelet peroxidase activity. Remission was not induced by mini-COAP or VP-16 and the patient died of measles pneumonitis. The patient's blasts took typical appearance of megakaryoblasts later in the course, although some of them retained the ability of hemophagocytosis observed in the original blasts. This case is considered to be quite atypical since leukemic cells with active hemophagocytosis, megakaryoblastic appearance and t(16; 21) (p11; q22) have not been reported in the literature. PMID- 2313909 TI - [Sick sinus syndrome as an initial symptom of B-cell malignant lymphoma involving the heart]. AB - We present a rare case of B-cell malignant lymphoma in whom lymphoma cell infiltration into heart caused sick sinus syndrome (S.S.S) as an initial symptom and premortem diagnosis of heart involvement was made. A 62-year-old woman was admitted to the orthopedic hospital because of pain in the lower extremities and discomfort in the chest. Chest roentgenogram showed an enlarged cardiac shadow and electrocardiogram (ECG) showed a sinus node dysfunction. A diagnosis of S.S.S. was made by the examination of sinus node recovery time. Myelography disclosed complete block between the 3rd and 4th lumbar vertebra. Pacemaker was inserted and laminectomy was done. The diagnosis of malignant lymphoma was made by the cytological study of the resected tissue. Gallium isotope study showed markedly increased isotope uptake in heart and abdomen. After chemotherapy the enlarged shadow of heart reduced in size and the uptake of gallium disappeared. ECG showed a sinus regular rhythm. Afterwards her general condition got worse and leukemic convergence of malignant lymphoma occurred. Monoclonal antibody study of these cells disclosed positive CD 19 (OK B1), CD 20 (OK B4), and surface IgM lambda. PMID- 2313910 TI - [Aplastic anemia probably induced by allopurinol in a patient with renal insufficiency]. AB - A rare case of aplastic anemia which was considered to be induced by allopurinol was reported. A 48-year-old female had suffered from urolithiasis and chronic renal insufficiency. She was administered allopurinol for hyperuricemia for 4 months, and subsequently developed severe pancytopenia and bone marrow suppression. After stopping of allopurinol administration, she was administered prednisolone but died of gastro-intestinal tract bleeding and sepsis on the 21th hospital day, without hematological recovery. PMID- 2313912 TI - [Clinical significance of bone density]. PMID- 2313911 TI - [Blastic crisis of primary myelofibrosis associated with multiple myeloblastomas ]. AB - The patient is a 71-year-old female who underwent splenectomy due to splenomegaly 32 months after diagnosed as having primary myelofibrosis. On examination she was found to have massive skin nodules, lymph nodes swelling and an enlarged liver with an abnormal hematologic profile as follows: RBC count 3.68 x 10(6)/microliters; WBC count 151 x 10(3)/microliters with 11% blasts; and platelet count 42 x 10(3)/microliters. The bone marrow aspirate showed a hypocellular marrow with 19.2% blasts. Histological examination of the skin nodules revealed that they were myeloblastomas, thus suggesting leukemic transformation of primary myelofibrosis. Her WBC count dropped to about 20 x 10(3)/microliters through treatment with vindesine, cyclophosphamide, 6 mercaptopurine and prednisolone, but it did not drop further. Treatment with dexamethasone remarkably regressed the myeloblastomas, but she died of heart failure 4 months after diagnosis of leukemic transformation of primary myelofibrosis. The autopsy findings showed the formation of numbers of myeloblastomas in both the systemic fatty tissue and dura mater as well as extramedullary hematopoiesis in liver and lymph nodes. A rapid development of splenomegaly in a patient with primary myelofibrosis seems to be associated with leukemic transformation. PMID- 2313914 TI - [Renal osteodystrophy]. PMID- 2313913 TI - [The history and present status of bone densitometry]. AB - Measurement of bone mass would be playing a major role in the field of research and clinical decision making of metabolic bone diseases, especially osteoporosis. As the magnitude of bone loss and the response to treatment are different from site to site throughout the entire skeleton, it is important to know which bone should be measured by which technique. Although values of BMD at various sites in the skeleton are significantly correlated, measurement at the actual site of fracture should be the most accurate way to predict fracture risk. New techniques and machines are now still under-developing and highly precise and site specific measurement of BMD may provide the predictive power needed for assessing fracture risk in individual subjects. PMID- 2313915 TI - [Diagnostic imaging of 67 Ga scintigraphy and CT x-ray]. PMID- 2313916 TI - [Assessment of bone scintigraphy showing markedly increased accumulation in mandibular lesion of cementifying fibroma]. AB - This report concerns two cases of cementifying fibroma showing markedly accumulation of 99mTc -MDP in mandibular lesions. The bone scintigraphic and histopathological findings are presented and discussed. PMID- 2313918 TI - [Microdensitometric method (MD method) of the second metacarpal bone]. AB - In Japan, microdensitometric method of the second metacarpal bone was developed 9 years ago to determine the degree of bone atrophy. This noninvasive method has some disadvantages such as precision of measurement of bone on X-ray film and determination of appendicular cortical bone, but is able conveniently to measure the bone density of the whole Japanese. One of 7 parameters in MD method, sigma GS/D is most important to evaluate and to follow up the condition of atrophy of cortical bone. We should investigate further the scientific base of MD method, for available tools in treatment of osteoporosis. PMID- 2313917 TI - [A case of osteosarcoma following radiation therapy]. AB - A case is presented in whom a new malignant neoplasm developed in fields of prior irradiation. The tumor was histologically diagnosed as osteosarcoma. This case satisfied the criteria of the radiation induced sarcoma proposed by Maehara et al. PMID- 2313919 TI - [SPA method; monitoring of bone mass during the treatment of osteoporosis]. AB - Accuracy and precision are indispensable to evaluate bone mass by non-invasive bone mineral measurement. In this paper, the methodological problems, such as measuring site and positioning errors of bone are described. Furthermore, the methods of monitoring of bone mass during ADFR treatment and double blind study for osteoporosis are also discussed. PMID- 2313920 TI - [Dual photon absorptiometry]. AB - BMC and BMD of the total body bone and lumbar spine were measured in normal control and patients with metabolic bone diseases by DPA (Dichromatic Bone Densitometer Model 2600, Norland corporation). Also, total body fat mass was measured in patients with obesity. We discussed basic technical problems and showed some data to assess patients with metabolic diseases known to affect the skeleton such as primary and secondary hyperparathyroidism. DPA is useful technique to assess patients with metabolic bone diseases and to monitor the efficacy of treatments. PMID- 2313921 TI - [Bone mineral determination using dual energy X-ray absorptiometry (DEXA)]. AB - To quantify the appendicular and axial bone mineral with good accuracy and precision, dual energy X-ray absorptiometry (DEXA), DCS-600 (Aloka) for the radius, mainly composed of cortical bone, and QDR-1000 (Hologic) for the lumbar vertebrae, mainly composed of trabecular bone, was used. Bone loss with aging was earlier in females than that in males, and it was also more prominent in the lumbar vertebrae than that in the radius. Furthermore, the vertebral fracture rate could be evaluated by calculating percentile of an individual bone mineral density to the peak bone mass. Thus, the bone mineral determination using DEXA in both the appendicular and axial bone will provide a useful information in the assessment of bone loss, and the detection of the patients with high risk of fracture in osteoporosis. PMID- 2313922 TI - [Quantitative computed tomography for bone mineral assessment]. AB - A precise method of measuring vertebral mineral content by quantitative computed tomography (QCT) using reference phantom was conducted. In order to minimize the error, the lumbar spine to be measured should be brought to the center of CT gantry, the phantom should be brought into close contact with the subject for measurement, scanning should be carried out on 10 mm slice thickness and the region of interest should be selected as large as possible. Comparison of QCT values among various CT scanners was difficult. This method was useful for the measurement of trabecular mineral content of lumbar vertebra in clinical practice. PMID- 2313923 TI - [MR imaging of bone and soft tissue tumors]. AB - One hundred sixty-one patients with tumors of bone or soft tissues underwent MRI. We believe to be able to differentiate benign from malignant lesions on the basis of imagings at internal, marginal, and peripheral properties. MR imagings demonstrated specific morphologic features that suggest the correct tissue diagnosis. MR imagings with STIR method or Gd-DTPA were more valuable. Because of the high contrast between the tumors and normal tissue, especially by STIR method, MRI provides improved detection and delineation of bone soft tissue tumors when compared to other diagnostic modalities. PMID- 2313925 TI - [Principle and instruments of bone densitometry]. AB - Various methods for measurement of bone densitometry have been developed over the past two decades. This paper discribes the basic principle, technical characteristics and clinical performance on the SPA, DPA, QCT and newly developed DEXA. Advantage of SPA is low cost with high precision, but the method is used to measure only the distal radius. QCT can measure only the trabecular bone from the cortex, but requires high radiation dose. DEXA is similar in concept to DPA, but affords many advantages, i.e. higher precision, higher resolution, shorter examination time and lower dose than the DPA. This new DEXA should allow more accurate and precise management in patients with metabolic bone diseases. PMID- 2313924 TI - [An evaluation of MR imaging of soft-tissue masses in extremities]. AB - We evaluated 22 soft-tissue masses in the extremities using magnetic resonance (MR) imaging. The twenty-two cases consist of 14 benign lesions and 8 malignant lesions. MR imaging is available to provide the representation of the extent of the masses, though characteristic diagnosis of them could not be identified. We think that there are more advantages to using MR imaging rather than computed tomography (CT) in the evaluation of soft-tissue masses in extremities. PMID- 2313926 TI - [MRI of lymphedema using short-TI-IR (STIR)]. AB - Thirty four cases with lymphedema of the extremities were examined with MRI at 0.5 tesla. On T1-weighted image, the enlarged subcutaneous tissue and the subcutaneous trabecular structures were seen in all cases. Moreover, the trabecular structures in the enlarged subcutaneous tissue showed low signal intensity on T1-weighted image and high signal intensity on T2-weighted image in all cases. Additionally, in 12 of 15 cases examined by Short-TI-IR (STIR) image, the trabecular structures and fluid collections in the subcutaneous tissue were shown more definitely in high signal intensity than by T2-weighted image. We consider MRI using STIR is to be useful in the evaluation of edematous disease. PMID- 2313927 TI - [Difference between T1 and T2 weighted MR images in avascular necrosis of the femoral head]. AB - T1 and T2 weighted MR images were compared in 32 hips with avascular necrosis, and the difference between them was discussed. In 27 of 32 hips, abnormal low intensity area in the affected femoral head is smaller in T2 weighted images than in T1 weighted images. The area of low intensity on T1 weighted image and high on T2 weighted image might be granuloma in reactive tissue and surrounding hyperemia. The difference between T1 and T2 weighted images must be taken into consideration especially in determination of the border of affected bone. PMID- 2313928 TI - [Screening for osteoporosis]. AB - Current status of the diagnosis and treatment of postmenopausal osteoporosis is reviewed, and screening for postmenopausal osteoporosis is discussed. Although prevention and treatment of osteoporosis have been extensively investigated, further knowledge and experience may be still needed for routine clinical application. PMID- 2313929 TI - [Proceedings of the 76th meeting of the Japanese Society of Gastroenterology. Tokyo, 29-31 March 1990. Abstracts]. PMID- 2313930 TI - Central effects of the neurotropic mycotoxin fumitremorgin A in the rabbit. (II). Effects on the brain stem. AB - In order to determine the main site of the convulsant action of the neurotropic mycotoxin fumitremorgin A, the role of the brain stem reticular formation was studied. In rabbits lightly anesthetized with urethane and chloralose, electrical stimulation of the reticular formation elicited burst discharges in the common peroneal nerve and in the tibial nerve. This facilitatory effect of electrical stimulation was markedly potentiated by intravenous administration of a small dose of FTA, before onset of actual convulsion. Under the influence of FTA, a remarkable increase in the spontaneous electrical activity of the midbrain reticular formation was observed. The firing pattern of some neurons in the reticular formation corresponded very well with abnormal burst discharges in the common peroneal nerve. These effects of FTA were inhibited by chlorpromazine (0.1 1.0 mg/kg, i.v.), diazepam (0.1-1.0 mg/kg, i.v.), mephenesin (5-10 mg/kg, i.v.) and pentobarbital (5-15 mg/kg, i.v.). It was concluded that FTA might activate some neurons in the midbrain reticular formation and that convulsive burst discharges in peripheral motor nerves resulted from abnormal activation of these neurons, although the role of the medullary reticular formation could not be excluded. PMID- 2313931 TI - Protective effect of S-adenosyl-L-methionine against CCl4-induced hepatotoxicity in cultured hepatocytes. AB - Effect of S-adenosyl-L-methionine disulfate tosylate salt (SAMe-ST) and L methionine (L-Met) on primary cultured rat hepatocytes were studied. In cultured hepatocytes treated with CCl4, SAMe-ST and L-Met suppressed the decrease in urea nitrogen secretion as well as the leakages of GOT and GPT. The membrane protective action of these two compounds was verified by the histological data. Failure of SAMe-ST to counteract CCl4-induced reduction of radioactive leucine incorporation into the trichloroacetic acid-insoluble materials in hepatocytes indicates that the observed effects of SAMe-ST or L-Met do not involve acceleration of protein synthesis. The present results indicate that SAMe-ST remarkably protects hepatocytes from CCl4-induced hepatotoxicity, probably by either changing the structure or compositions of membrane phospholipids or by modifying the interaction of CCl4 with the intracellular drug-metabolizing enzyme systems. PMID- 2313932 TI - Lipid peroxidation and generations of oxygen radicals induced by cephaloridine in renal cortical microsomes of rats. AB - To investigate whether oxygen radicals would be generated by cephaloridine (CER) in the renal cortical microsomes obtained from rats and whether the microsomal lipid peroxidation would be promoted by CER, the microsomes were incubated under a pure oxygen atmosphere in a medium containing the reduced nicotinamide adenine dinucleotide phosphate regenerating system, under various conditions. Generations of superoxide anion and hydrogen peroxide and malondialdehyde formation were all dependent on microsomal protein concentrations, incubation periods and CER concentrations. Scavengers of the microsomal lipid peroxidation induced by CER, (+)-cyanidanol-3, mannitol, sodium benzoate and N-acetyl tryptophan, which are scavengers of hydroxyl free radicals, inhibited the CER-stimulated lipid peroxidation in the microsomes. Histidine, a scavenger of hydroxyl free radicals and singlet oxygen, and alpha-tocopherol, reduced-glutathione and NN'-diphenyl-p phenylenediamine, the three of which are non-specific antioxidants, also inhibited the CER-stimulated lipid peroxidation in the microsomes. Accordingly, our findings may strongly support that CER generates not only superoxide anions and hydrogen peroxide but also hydroxyl free radicals in the kidney, and these generated oxygen radicals react with the membrane lipids to induce peroxidation and nephrotoxicity. PMID- 2313933 TI - Inhibitory effects of nisoldipine and saralasin on angiotensin II-induced antidiuresis in anesthetized dogs. AB - Inhibitory effects of the calcium channel blocker nisoldipine on angiotensin II induced antidiuresis were investigated in anesthetized dogs, and the findings were compared with those of saralasin. Intrarenal arterial infusion of 10 ng/kg/min angiotensin II resulted in marked decreases in renal blood flow (RBF) and urine formation, with a relatively moderate decrease in glomerular filtration rate. There were marked reductions in the fractional excretion of lithium, which is used as an index of the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. Nisoldipine (50 ng/kg/min) administered intrarenally produced a partial inhibition on the decreased response of RBF to angiotensin II. The peptide-induced decreases in urine flow, urinary excretion of electrolytes and fractional excretion of electrolytes were abolished by nisoldipine. In contrast, when saralasin was administered intrarenally at 10 ng/kg/min, a dose which could partially inhibit the angiotensin II-induced decrease in RBF to the same extent as seen with nisoldipine, the antagonist attenuated, but did not abolish, the antidiuretic action of angiotensin II. Significant decreases in urine formation by angiotensin II were observed, even in the presence of saralasin. These results suggest that nisoldipine, unlike saralasin, preferentially interferes with the stimulatory effect of angiotensin II, as related to the renal tubular reabsorption of sodium and water. PMID- 2313934 TI - Acid secretagogue action of structurally gamma-aminobutyric acid (GABA)-related compounds in rats. AB - The properties of GABA related compounds on gastric function were studied in standardized perfused rat stomach preparations. Intravenous GABA (400 mg/kg) produced a rapid increase in acid secretion. Acid secretagogue actions of 3 aminobutyric acid and 2-aminobutyric acid were less potent than that of GABA. Intravenous injection of 5-amino-n-valeric acid (400 mg/kg) stimulated gastric acid secretion, but 6-amino-n-caproic acid was inactive. Isoguvacine (40 mg/kg, s.c.) stimulated acid output, whereas guvacine, an isomer of isoguvacine, did not. Systemically administered 3-hydroxy-GABA and beta-(p-chlorophenyl)-GABA (PCPGABA) showed significant secretagogue actions. Acid responses to GABA-related compounds were significantly reduced by surgical truncal vagotomy and completely antagonized by atropine. The acid responses to PCPGABA and isoguvacine were partially augmented by yohimbine and propranolol. These results suggest that the secretagogue action of GABA is mimicked by structurally GABA-related compounds, which is mediated through cholinergic receptors, with slight implication of alpha 2 and beta-adrenoceptor mechanisms. PMID- 2313935 TI - Histamine increases vascular tone and intracellular calcium level using both intracellular and extracellular calcium in porcine coronary arteries. AB - Effects of histamine on the tone and intracellular calcium level (Ca2+i) in porcine coronary arteries were simultaneously investigated by use of the fura-2 microscopic fluorometric method. Histamine (10(-6)-10(-4) M) induced concentration-dependent increases in tone and Ca2+i, but these responses were not sustained. Histamine induced a larger contraction than did KCl with a similar increase in Ca2+i. Depletion of the caffeine-sensitive Ca2+ store with ryanodine (3 x 10(-5) M) and repetitive applications of caffeine (2.5 x 10(-2) M) scarcely affected contractile and Ca2+i responses to histamine. In Ca2(+)-free medium or in the presence of verapamil (10(-6) M), histamine produced a briefer increase in Ca2+i and a smaller contraction than in normal medium. When histamine or caffeine was repetitively applied in Ca2(+)-free medium, the first application produced an increase in Ca2+i but the second application produced no increase. Although caffeine increased Ca2+i after repetitive histamine applications, histamine failed to increase Ca2+i after repetitive caffeine applications in Ca2(+)-free medium. These results indicate that vascular contraction induced by histamine may involve the following mechanisms: an increase in Ca2+ influx through Ca2+ channels, release of Ca2+ from the intracellular Ca2+ store which has an interaction with the caffeine-sensitive Ca2+ store, and sensitization of contractile proteins to Ca2+. PMID- 2313936 TI - Effects of calcium antagonists, felodipine and nicardipine, on cerebral circulation in dogs. AB - The effects of a calcium antagonist of the dihydropyridine type, felodipine, on the cerebral circulation were studied in comparison with those of nicardipine in pancuronium-bromide immobilized unanesthetized dogs. Felodipine (0.3-10 micrograms/kg, i.v.) and nicardipine (0.3-10 micrograms/kg, i.v.) produced a dose related decrease in mean blood pressure with almost equal potencies. However, at a dose of 3 micrograms/kg, felodipine produced a more prominent increase in cerebral blood flow (CBF) than nicardipine. Decreases in cerebral vascular resistance were significantly greater in the felodipine group at doses of 0.3 and 3 micrograms/kg, when compared with the nicardipine group. Cerebral oxygen consumption calculated by multiplying the arterio-venous difference of oxygen content by CBF was increased by these two drugs, but the changes were minimal. These data suggest that the increase in CBF produced by felodipine and nicardipine was primarily due to the direct dilatation of the cerebral blood vessels. PMID- 2313937 TI - Centrally mediated inhibitory effect of 5-[2-(diethylamino)ethyl]amino-5,11 dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride (KW-5805) on gastric acid secretion in rats. AB - KW-5805, 5-[2-(diethylamino)ethyl]amino-5,11-dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride, is a new tricyclic compound with antiulcer activities. Its effect on stimulated gastric acid secretion was investigated in the perfused stomach of anesthetized rats. KW-5805 at 0.3-10 mg/kg, i.v., dose dependently inhibited gastric acid secretion stimulated by 2-deoxy-D-glucose (2 DG). On the other hand, the compound at 10-20 mg/kg, i.v., exerted a moderate decrease in gastric acid secretion stimulated by bethanechol; and at 10 mg/kg, i.v., it produced no change in gastric acid secretion evoked peripherally by vagal electrical stimulation. When applied intracerebroventricularly at 1-5 micrograms/rat, this compound dose-relatedly reduced gastric acid secretion stimulated by 2-DG. Three main metabolites (KF-10504, KF-9530 and KF-10847) of KW 5805 at 1 mg/kg, i.v., caused no significant decrease in gastric acid secretion stimulated by 2-DG. Doxepin, a tricyclic compound, definitely depressed the 2-DG stimulated gastric acid secretion at 1 mg/kg, i.v. It is suggested that intravenous administration of KW-5805 inhibits gastric acid secretion stimulated by 2-DG, mainly via centrally mediated mechanisms, and that biotransformation of KW-5805 to the metabolites contributes little to the development of the antisecretory effect. PMID- 2313938 TI - Inhibitory effects of OKY-046 on spasmogen-induced bronchoconstrictions in sensitized and non-sensitized guinea pigs. AB - We examined the effect of thromboxane A2 (TXA2) synthetase inhibitor, OKY-046, on bronchoconstriction induced by antigen and various spasmogenic mediators in guinea pigs in vivo. Further, inhibitory activities of OKY-046 on contractions of isolated tracheae and lung parenchymal strips induced by various contractile agents were also investigated in vitro. OKY-046, but not indomethacin, significantly inhibited antigen-induced bronchoconstriction in a dose-dependent manner. Moreover, OKY-046 attenuated bronchoconstrictions induced by peptide leukotrienes (LTs) and platelet activating factor (PAF), but not those by histamine, prostaglandin D2 (PGD2) and STA2 (a stable TXA2 mimetic agent). Although contractile responses induced by spasmogens such as peptide LTs, PAF and histamine were not influenced by OKY-046 in isolated tracheae, OKY-046 elicited significant and concentration-dependent inhibitions against contractile responses induced by peptide LTs and PAF in isolated lung parenchymal strips. These results suggest the possible involvement of TXA2 in the development of anaphylactic bronchoconstriction in sensitized guinea pigs. PMID- 2313939 TI - Reconsideration of vascular selectivity of dihydropyridine calcium antagonists: comparison of cardiovascular profile of mepirodipine, a novel dihydropyridine consisting of a single stereoisomer with (+)-(S)-(S) conformation, with those of nifedipine and nicardipine. AB - The coronary vasodilator effect and negative chronotropic, inotropic and dromotropic effects of mepirodipine, the single stereoisomer of a novel dihydropyridine Ca antagonist, were compared with those of nifedipine and nicardipine using canine isolated, blood-perfused heart preparations. Drugs were injected into each nutrient artery. In the sinoatrial node preparation, the dose producing a 15% decrease in sinoatrial rate was 1.3, 6.5 and 2.5 micrograms for mepirodipine, nifedipine and nicardipine, respectively. In the papillary muscle preparation, the dose causing a 50% decrease in developed tension was 44, 6.5 and 54 micrograms for mepirodipine, nifedipine and nicardipine, respectively. The dose causing a 50% increase in blood flow through the anterior septal artery was 0.26, 0.18 and 2.0 micrograms for mepirodipine, nifedipine and nicardipine, respectively, while the time required for return to half maximum at the above dose was 13.1, 1.8 and 4.1 min, respectively. In the atrioventricular node preparation, the dose producing a 50% increase in AH interval was 1.6, 2.4 and 3.7 micrograms for mepirodipine, nifedipine and nicardipine, respectively. These results indicate that mepirodipine is a potent and long-lasting dihydropyridine Ca antagonist, whose vascular selectivity is highest against cardiac contractility, but less selective against sinoatrial node automaticity and atrioventricular nodal conduction, compared with nifedipine. PMID- 2313940 TI - Effects of GABA antagonists and structural GABA analogues on baclofen stimulated gastric acid secretion in the rat. AB - The effects of GABA receptor antagonists (bicuculline and phaclofen) and structural GABA-analogues on baclofen stimulated gastric acid secretion were studied in standardized perfused rat stomach preparations. Pretreatment with bicuculline, a GABAA-receptor antagonist, in the doses of 1 and 3 mg/kg, subcutaneously, had no influence on the gastric acid response to baclofen. In addition, phaclofen, a GABAB antagonist, in the doses of 3 to 30 mg/kg, intravenously, was found to have no significant effect on the acid response to baclofen. However, GABA-analogues (MOPS and ABA; 10-30 mg/kg, i.v.) and lipophilic GABA derivatives structurally related to beta-amino acids (APPA and APHA; 30 mg/kg, i.v.) significantly counteracted the secretagogue action of baclofen. Further experiments on APPA action showed that the antisecretory effect of APPA could be overcome by higher doses of baclofen. APPA did not affect bethanechol stimulated acid secretion. These results suggest that the secretagogue action of baclofen is independent to GABAA- and GABAB-receptors and that APPA may interact with baclofen in regulation mechanisms of acid secretion, although further investigations are necessary to define the mode of action of APPA on the GABA-ergic system. PMID- 2313941 TI - Changes in coagulative and fibrinolytic activities in Triton WR-1339-induced hyperlipidemia in rats. AB - Changes in coagulative and fibrinolytic activities were studied in rats with hyperlipidemia induced by Triton WR-1339 (T-WR). After intravenous injection of T WR (150, 200 or 300 mg/kg) into S.D. rats, dose-related increases in plasma lipids (total cholesterol, triglyceride, free cholesterol and phospholipid) were observed. In hyperlipidemic rats that received 300 mg/kg of T-WR, decreases in red blood cell count and Hb value were found. Significant increases in the ma value of the thromboelastogram and the fibrinogen level were observed in these T WR treated rats. The alpha 2-plasmin inhibitor activity was found to decrease dose-relatedly. These results indicate that T-WR induced hyperlipidemia in rats is accompanied with an increase in coagulative activity and an indirect enhancement of fibrinolytic activity. PMID- 2313942 TI - Antiulcer activity of eel-calcitonin (elcatonin) is associated with enhanced gastric mucosal PGE2 generation in the rat. AB - Elcatonin is a newly synthetized peptide that prevents experimental ulcer formation. In this study, we examined the influence of elcatonin on endogenous prostaglandin biosynthesis by the gastric mucosa with respect to its antiulcer activity. Control levels of PGE2 generation for the fundic and antral mucosa were 302 +/- 12 and 465 +/- 28 ng/g tissue/min, respectively. Pretreatment with elcatonin resulted in a dose-dependent increment in gastric mucosal PGE2 generation. We conclude that the antiulcer effect of elcatonin is probably due to its ability to enhance endogenous prostaglandin synthesis in the gastric mucosa. PMID- 2313943 TI - Effect of bifemelane hydrochloride on an injury of the liver caused by ischemia reperfusion in rats. AB - In the liver ischemia-reperfusion model, the lipid peroxide level increased during ischemic periods, while a greater increase was observed during reflow periods. The increase in the cytochrome b5 content was observed during ischemia and reflow periods. On the contrary, the cytochrome P-450 content remained unchanged during ischemic periods, but decreased during reflow periods. Bifemelane suppressed the elevation of the lipid peroxide level, the cytochrome b5 content and the decrease in cytochrome P-450 content during the period of reperfusion. PMID- 2313944 TI - Uremic changes induced by experimental urinary retention in goats. AB - The disease process of urinary retention resulting in uremia reported in cattle was studied clinically, clinico-pathologically and pathologically in 4 male goats with artificial urethrobstruction (UO). The blood urea nitrogen (BUN) and serum creatinine values increased at constant rates (mean rates: 29.1 mg/dl/day and 1.6 mg/dl/day, respectively) from the initial stage. These increased levels were thought to be the most useful indicator for the diagnosis of the uremic stage. The serum sodium and chloride values decreased gradually after UO. The glucose and potassium values increased remarkably later than in the intermediate stage. Rupture of the bladder caused severe dehydration. The animals died between 8 to 13 days post-urinary retention. Unusual respiration and heart beat, and severe nervous signs were seen at moribundity. Gross lesions of the urinary organs were characterized by the pressure of retained urine and hemorrhage and edema in the subcutaneous tissues, skeletal muscles and some other organs. To study the effect of urethrotomy, 3 male goats were relieved from UO 3 or 4 days after UO operation. The animals became capable of reurination and recovered from the uremic condition within 4 days. PMID- 2313945 TI - Twenty cases of equine osteoarthrosis detected at autopsy. AB - A pathological study was performed on osteoarthrosis detected at autopsy in 20 horses whose ages ranged from 21 days to 17 years old. They were asymptomatic on the joints except in 3 animals, and autopsied after death or sacrificed due to accidental fracture or other diseases. Lesions of osteoarthrosis were recognized in all horses, which tended to increase in incidence and severity according to age. Lesions were concentrated at hinged joints such as the elbow, fetlock, and hock. Synovial fossae and ulcerative lesions were observed on each opposite articular cartilage, forming the so-called mirror image. Linear erosions regarded as a secondary one were frequently observed on the cartilages. Histologically, the lesions were classified into 4 phases, 1) edematous degeneration, 2) crevice formation, focal necrosis, erosion of cartilage, 3) ulcerative changes, 4) regenerative changes of cartilage in foals and proliferation of fibrous or adipose tissue on the denuded subchondral bone in aged horses. By toluidine blue stain, decreased acid mucopolysaccharide was suggested in cartilaginous matrix around the lesions. From the results, it was concluded that the disease was a disorder of articular cartilage accompanied with hypoplasia of articular subchondral bone. PMID- 2313946 TI - Development of a special alligator forceps for removal of pulmonary heartworms in very small dogs. PMID- 2313947 TI - Enzyme-linked immunosorbent assay for evaluation of immunity in mice vaccinated with blackleg vaccine. PMID- 2313948 TI - Impairment of lymphocyte blastogenesis in road-transported calves observed with a whole blood culture technique. PMID- 2313949 TI - Immunohistochemical studies on the development of endocrine cells in the thyroid and parathyroid glands in the golden hamster. AB - The development of endocrine cells in the thyroid and parathyroid glands in the golden hamster was studied immunohistochemically in relation to the formation of these glands. The thyroid was formed on day 9 of gestation by the ventral outpocketing of the foregut between the first and second branchial pouches. The thyroid epithelial cells were faintly thyroglobulin-immunoreactive on day 10.5 of gestation. This immunoreaction became intense thereafter, but was almost confined to the cytoplasm of epithelial cells until birth. It appeared in the follicular lumen in newborn animals. The ultimobranchial body was derived from the fifth pouch and fused with the thyroid on day 12 of gestation. Calcitonin immunoreactive cells first appeared on day 14 of gestation in the dorsomedial part of the thyroid derived from the ultimobranchial body and increased in number and intensity thereafter. Somatostatin-immunoreactive cells also appeared in the dorsomedial part of the thyroid derived from the ultimobranchial body on day 13 of gestation, and increased in number in newborn animals, but decreased thereafter. The parathyroid was derived from the third pouch, situated on day 13 of gestation on the dorsolateral side of the thyroid, and surrounded by a common capsule with the thyroid. Parathormone-immunoreactive cells first appeared on day 15 of gestation in the parathyroid and increased in number and intensity after birth. PMID- 2313950 TI - Detection of bovine antibodies to the outer membrane of ruminal Bacteroides succinogenes by enzyme-linked immunosorbent assay (ELISA). AB - The enzyme-linked immunosorbent assay (ELISA) was used to detect bovine serum antibodies directed to the outer membrane antigen of a ruminal bacteria, Bacteroides succinogenes. The outer membrane antigen of B. succinogenes was highly reactive against homologous antiserum, compared with rabbit sera raised against B. ruminicola subsp. ruminicola, B. ruminicola subsp. brevis and Selenomonas ruminantium. The titers of sera from colostrum-deprived calves were negligible level, while those of sera from colostrum-fed calves were relatively high. The mean titer of sera from 10 day-old calves was significantly (p less than 0.01) higher than that of 40 day-old calves, and was significantly (p less than 0.01) lower than that of adult cattle. The mean titer of sera from dairy cows which fed high-roughage diet was higher than that of feedlot cattle which fed high-concentrate diet. These results suggest that the antibodies against the outer membrane antigen of B. succinogenes transfer to calves via the colostrum, and that the titers of cows are affected by the way of feed management. PMID- 2313951 TI - Hematology in sika deer (Cervus nippon yesoensis Heude, 1884). AB - Blood samples were taken from 78 wild and 21 farmed sika deer (Cervus nippon yesoensis) using ketamine-xylazine sedation during their excited (82 deer) and resting (17 deer) states. Red cell count (RBC), hemoglobin (Hb), packed cell volume (PCV) and mean corpuscular volume (MCV) were significantly higher and mean corpuscular hemoglobin concentration (MCHC) was lower in excited deer than in resting deer. There was no significant difference in total leukocyte count (WBC) between excited and resting wild males, while a marked increase of WBC with neutrophilia was observed in excited wild females. RBC and PCV were significantly higher and MCH was lower in excited males than in excited females. In wild deer, WBC was significantly higher in females than in males, but there was no significant difference in WBC between farmed males and females. Sex differences in the hematological parameters were not observed in fawns (10 months). PMID- 2313952 TI - Histopathology of spontaneous panarteritis in beagle dogs. AB - Spontaneous focal panarteritis was noted in small and medium-sized arteries including extramural and intramural coronary arteries, and arteries in bone marrow, leptomeninges of spinal cord, meninges of medulla oblongata and tunica albuginea of epididymis of 17 out of 925 beagle dogs used for various toxicity studies. The arterial lesion consisted of varying inflammatory processes in all of the arterial wall and was characterized by intimal fibrinoid necrosis in acute cases and intimal fibrous thickening in chronic cases with varying population of inflammatory infiltrates in the arterial wall. The infiltrates included plasma cells, lymphocytes, macrophages and neutrophils. Periarterial inflammatory cells of the affected arteries showed positive reactions to IgG or IgM. Morphological similarities between spontaneous and drug-induced arterial lesions might confuse the evaluation for vascular toxicity of various chemicals. Therefore, detailed description of the morphology and distribution of spontaneous arterial lesions in the beagle dogs seems to be important for the pathological basis on safety assessment. PMID- 2313953 TI - Prevalence and distribution of bovine coccidia in Japan. AB - A field survey was carried out on prevalence of bovine coccidia in 9 prefectures of Japan in the autumn of 1985. A total of 1,015 fecal samples was obtained from dairy and beef cattle more than 2 weeks old. Coccidial oocysts were found in 59.0% of all the samples examined. There were no significant differences in the prevalence between dairy and beef cattle of the same age group. The prevalence was the highest in the animals between 6 and 11 months old and decreased to 25% in those more than 24 months old. In the majority of the samples positive for oocysts, OPG (the number of oocysts per gram of feces) was less than 200. No clinical coccidiosis was found except in a few cases. Eleven Eimeria and one Isospora species were identified. Of these species, E. bovis and E. ellipsoidalis were the most prevalent, followed by E. aubrunensis, E. brasiliensis, and E. cylindrica in all the prefectures. The other species identified were E. canadensis, E. alabamensis, E. zuernii, E. wyomingensis, E. bukidnonesis, E. subspherica, and Isospora sp. in the order of frequency. Isospora sp. will be a pseudoparasite caused by the contamination with feces of passerine birds. PMID- 2313954 TI - Studies on the changes in myocardial oxygen tension. AB - An arterial oxygen tension (PO2) sensor was used to measure the myocardial PO2 at three sites in the left ventricle supplied by the paraconal interventricular branch of the left coronary artery, cranial descending coronary artery (CDCA): a subendocardial site, a subepicardial site and an intermediate point in the left ventricular wall. At first, the PO2 sensor had been compared with the values from a blood gas analyzer. The regression equation Y = 1.4X-4.9 with a correlation coefficient of 0.993 indicated a high correlation between these two measurements. The PO2 of the arterial blood in the left ventricular cavity was assigned an index value of 100%. The PO2 was about 70% in the subendocardial myocardium, about 15% in the mid-ventricular wall myocardium and 9% in the subepicardial myocardium, demonstrating a decreasing PO2 gradient from the endocardial to the epicardial surface. A transient occlusion of the CDCA confirmed the pathway of myocardial oxygen supply. In the mid-ventricular and subepicardial myocardium, marked hypoxia occurred after occlusion of the CDCA. Release of the occlusion resulted in a rapid return to the normal PO2 level. The oxygen supply to these sites is strongly influenced by coronary artery blood flow. The PO2 in the subendocardial myocardium was not dependent on the cranial descending coronary artery. Oxygen appears to be probably supplied through arterial blood in the left ventricle via the endocardium. PMID- 2313955 TI - Effects of osmolality on water, electrolytes and VFAs absorption from the isolated ruminoreticulum in the cow. AB - Effect of the osmolality on the absorption of water, electrolyte and VFAs from the isolated ruminoreticulum under normal feeding condition were investigated in a series of the study to evaluate the rumen as a potential site of absorption in oral fluid therapy of adult cattle. Thirty of 40 l of the test solutions with varying osmotic pressure (100, 200, 300 and 500 mosmol/L, pH 6.8) were prepared using different concentrations of electrolytes and VFAs. These were infused into the isolated and emptied ruminoreticulum, and the absorption rate of water and each components were studied for 3 hrs. Marked absorption of water was observed with solutions more hypotonic than rumen fluid, the extent of which was more extensive with less osmotic pressure; the absorption rate as high as 47.6% was obtained with a solution 100 mosmol in osmotic pressure. When hypertonic solution (500 mosmol/L) was infused, however, water was transported on the contrary from the blood to the rumen. Absorption rates of electrolytes such as Na, K and Cl were increased according to the elevation of osmolalities and their concentrations in the test solutions. VFAs were also absorbed in large quantities (23.9-74.5%) in any test solutions, though the absorption rates were significantly decreased with the elevation of osmolalities. These results may indicate that the ruminal wall has a high absorptive function for water, electrolytes and VFAs when the osmolalities and the concentration of solutes in the ruminal fluid are maintained within a certain range. Furthermore, it is thought that they may work as a rational support for a possible oral fluid therapy even in adult cows. PMID- 2313956 TI - [Epidemiological study on tuberculosis in Tochigi Prefecture. Part II: The changes in tuberculosis incidence and analysis of relating factors]. AB - The incidence rate of tuberculosis has been increasing in recent 5 years in Tochigi Prefecture. The author intends to clarify the factors effecting the changes of tuberculosis incidence during the period from 1962 to 1987 by analyzing the annual statistics of tuberculosis registry and implementation of tuberculosis control programme. The results thus obtained are as follows: 1. The incidence rate of tuberculosis in Tochigi Prefecture has increased in the past 5 years especially in the younger age group of 0-19 and older age group of 50 and over. The increase can be explained by the recurrence of the disease occurred when they were young, most likely due to incomplete treatment, and secondary infection to young family contacts. 2. The positive rate of tubercle bacilli was higher in Tochigi Prefecture than the rate in whole Japan during the period from 1979 to 1983, which was resulted from the delay in detection. 3. Frequency of visits to patients by public health nurses, numbers of X-ray and bacteriological examinations had decreased during the same period when the incidence rate of tuberculosis increased. 4. Continuous efforts to reinforce the tuberculosis control programme, especially X-ray and bacteriological examination for high risk population, such as family contacts, cleaners and barbers is essential in Tochigi Prefecture. PMID- 2313957 TI - [The efficacy of X-ray signs for differential diagnosis of small lung cancer and tuberculoma. Committee for Lung Cancer Mass Screening, JATA]. AB - In order to evaluate the efficacy of X-ray signs for the differential diagnosis of small lung cancer from tuberculoma, a cooperative study was carried out. X-ray films of 64 cases (lung cancer 35, tuberculoma 29) were read by 11 experienced chest physicians independently. The positivity of various X-ray signs were assessed respectively and obtained data were analysed with ROC analysis method. "Ill defined contour", "unevenness of density", "paleness" were proved to be relatively useful as a diagnostic tool, but "notch", "pleural indentation" were not useful in differentiating lung cancer from tuberculoma. It was also noted that great interindividual variations existed on the judgements of X-ray signs among chest specialists, and the conquest of which may be a crucial key for the universal validity of these signs. PMID- 2313958 TI - [A case of tuberculous pericarditis]. AB - A case of tuberculous pericarditis successfully managed with medical treatment alone was reported. A 78-year-old male was admitted because of cough, dyspnea and fever. Chest X-P and echocardiogram revealed massive pericardial effusion. His clinical symptoms and signs suggested cardiac tamponade. Mycobacterium tuberculosis was detected from pericardial fluid. ADA activity in pericardial fluid was high. Thoracic CT scan showed tracheobronchial, pretracheal, paratracheal and superior mediastinal lymph-node swelling. The diagnosis of tuberculous pericarditis was confirmed. Anti-tuberculous therapy consisting of INH, RFP, EB in combination with prednisolone was started. One month later pericardial effusion was controlled and six months later he was in good clinical condition without surgical treatment. PMID- 2313960 TI - [Diagnostic usefulness of the bronchoscopy for pulmonary tuberculosis]. AB - We have experienced 83 patients with pulmonary tuberculosis in last 22 months. A rapid diagnosis of pulmonary tuberculosis was established in 14 (16.9%) out of 83 patients by bronchoscopic examinations. Out of 30 bronchoscopic examinations, exacerbation of the chest X-ray findings was seen in 4 patients, however there was no significant unfavourable effects on the results of treatment. A survey on the use of bronchoscopy for diagnosing pulmonary tuberculosis was undertaken through a questionnaire distributed to about 90 hospitals in Japan. Only a few exacerbation was experienced by TBLB, BAL, etc., in some hospitals. Above results suggests that bronchoscopy is a useful procedure for the rapid diagnosis of pulmonary tuberculosis. PMID- 2313959 TI - [Diagnostic value of bronchoscopy in diagnosis of pulmonary tuberculosis: bronchial aspirate, bronchial washing and transbronchial lung biopsy]. AB - The diagnosis of pulmonary tuberculosis is confirmed by the detection of Mycobacterium tuberculosis in sputum. Bronchoscopy has been used for diagnosis of various pulmonary diseases. The value of bronchoscopy such as bronchial aspirate, bronchial washing and transbronchial lung biopsy in diagnosis of pulmonary tuberculosis was evaluated, and the results were as follows: 1) One hundred ninety cases were investigated bronchoscopically due to suspicion of pulmonary tuberculosis with sputum negative smear and 92 cases were confirmed to be pulmonary tuberculosis. 2) Out of 91 cases examined by bronchial aspirate and 46 cases by bronchial washing, smear positivity was 20.9% and 23.9% and culture positivity was 58.2% and 84.8%, respectively. Transbronchial lung biopsy showed positive findings of tuberculosis in 75.8% out of 33 specimens. 3) Out of 88 sputa taken before bronchoscopy and 50 sputa after bronchoscopy, smear positivity was 0% and 12%, and culture positivity was 54.5% and 40% respectively. Gastric lavage culture positivity was 29.4% in 17 cases examined. 4) Diagnosis of tuberculosis was made rapidly in 28 cases (30.4%) by smear positive results of bronchial aspirate, bronchial washing and sputa after bronchoscopy, and relatively rapidly in 20 cases (21.7%) by transbronchial lung biopsy. PMID- 2313961 TI - [Basic and clinical evaluation of rapid diagnosis of tuberculosis by detecting tuberculostearic acid]. AB - Tuberculostearic acid (TSA) is known to be one of the characteristic lipid in the limited species of the order Actinomycetale, including Mycobacterium tuberculosis. We studied the significance of detecting TSA in the diagnosis of tuberculosis from clinical specimens collected from 791 patients with various respiratory diseases by using gas--chromatography/mass--spectrometry. By our method, the detectable limit of TSA was around 10(2)-10(3) bacilli of Mycobacterium tuberculosis, and our method is as sensitive as culture examination for tuberculosis. In sputa collected from patients with active pulmonary tuberculosis (n=169), TSA positively was around 90%, while less than 10% false positive ws also recognized. In pleural effusion (n=81) and bronchial washing (n=91) collected from patients with active tuberculosis, the positivity of TSA was around 70%. We could also detect TSA in about 30% of clinical specimens collected from patients suspected of tuberculosis. The diagnostic sensitivity of TSA for tuberculosis was similar to that of adenosine deaminase activity (ADA), while TSA was slightly superior to ADA in specificity. These findings indicate that detection of TSA from clinical specimens is useful to make rapid diagnosis of pulmonary tuberculosis. PMID- 2313962 TI - [The serodiagnosis of tuberculosis by enzyme-linked immunosorbent assay with tuberculin purified protein derivative]. AB - Tuberculin purified protein derivative (PPD) is a relatively crude antigen prepared from Mycobacterium tuberculosis and has species nonspecificity in immunological reaction. It is, however, more readily available than more highly purified materials. Therefore, the detection of IgG antibody to PPD was done by enzymed-linked immunosorbent assay (ELISA) and its diagnostic useful was evaluated in this study. The patients with active tuberculosis had significantly high titer of IgG antibody to PPD compared with healthy persons and the patients without tuberculosis (P less than 0.001). An upper limit of normal set (=cut-off titer) at 2 standard deviations above mean of logarithmic titers in 220 healthy adult subjects would result in positive test reactions on the sera from 78 of 100 patients with active tuberculosis. Although 8 of 39 with atypical mycobacteriosis would be positive, 6 of 7 were distinguished almost with tuberculosis by detecting antibodies to PPD from M. intracellulare and M. kansasii concurrently. The antibody titer increased after chemotherapy would be gradually reduced under the cut-off titer when culture of mycobacteria turned to negative and markers of inflammation became negative. In false-negative cases, 4 were patients with hypo gammaglobulinemia, 6 were with fresh tuberculosis before chemotherapy, 2 were with negative CRP in all clinical course and 4 were with bacilli needed over 7 weeks culture. From these results, this assay is helpful in the diagnosis of tuberculosis and a useful marker for judgment of clinical improvement, although detection of antibody has its limitations. PMID- 2313963 TI - [Tuberculin skin test of patients with active pulmonary tuberculosis and non tuberculous pulmonary diseases]. AB - The maximum diameter of redness of tuberculin skin test (PPD) was studied in patients with active pulmonary tuberculosis (TB) (257 cases) and with various non tuberculous pulmonary disorders (Non-TB) (328 cases). Negative rate of PPD (maximum diameter under 9 mm) was 9.3% in patients of TB; 6.5% in patients without underlying disorders and 16.3% with underlying disorders, which may affect the break-down of tuberculosis. In patients with miliary tuberculosis, the negative rate was high and PPD reaction became weaker in advanced patients and patients with pleurisy. High age, hypoalbminemia and lymphocytepenia in peripheral blood were the factors influencing the negative conversion of PPD skin test. In Non-TB patients, positive rate of PPD was similar between patients with and without past history of tuberculosis and the rate of patients with maximum redness over 35mm were about 10%, regardless of sex, age and disorders. But there was a difference in the positive rates of PPD between male and female; the positive rate of PPD skin test was highest in male with lung cancer, and there was a difference in the positive rate of PPD between the age groups in male, but there was no difference in females regardless of age with or without lung cancer. PMID- 2313964 TI - [Improvement in image-diagnosis of pulmonary tuberculosis]. AB - The results of experimental studies using a phantom suggest that the calculation of CT values pulmonary nodular shadows is not so reliable. The CT images of bronchogenous spread type tuberculous lesions reveal a regularity that corresponds to the bronchial branching pattern, called centrilobular shadows. On the other hand, hematogenous spread type lesions (miliary tuberculosis) distribute randomly regardless of bronchial branching. Centrilobular shadows, lobular shadows and multilobular shadows are the fundamental pattern of pulmonary tuberculosis on CT images. Shadows showing broncho-vascular dilatation as a projection of the tuberculous bronchitis are also important finding on CT images of pulmonary tuberculosis. Thus, CT is best suited for the precise image analysis of the disease. PMID- 2313965 TI - [Pulmonary Tuberculosis in foreigners]. AB - We studied the background and social problems of pulmonary tuberculosis in foreigners which we recently encountered at the National Chiba- Higashi Hospital and the Chiba Anti-tuberculosis Association. 1) The number of foreigners with pulmonary tuberculosis has been increasing year by year, one in 1983, none in 1984 and 1985, one in 1986, two in 1987 and four in 1988. 2) Most of these patients had been already infected or had some symptoms before their arrival to Japan. 3) Their background includes some serious social problems such as troubles in daily life coming from linguistic and cultural differences and economic difficulties, legal problems such as illegality of their stay in Japan, etc. 4) Most of the above cases could not be treated sufficiently because they are foreigners or because of their illegal stay. PMID- 2313966 TI - [Bactericidal activity of antituberculosis drugs against Mycobacterium avium complex]. AB - The bactericidal activity of antituberculosis drugs against two strains of M. avium complex 13008 (serotype 20) and 13016 (serotype 4), was observed using modified Dubos liquid medium (1.3 g of Dubos Broth Base (Difco) in 180 mil of distilled water plus 20 ml of bovine serum). The strains were most susceptible to antituberculosis drugs among M. avium complex strains (Table). The test strains were cultivated in Ogawa egg medium at 37 degrees C for 10 days, and growing colonies were homogenized by shaking with glass beads for 10 minutes and suspended in the modified Dubos liquid medium to a concentration of 2 mg wet weight per ml. The media containing drug and containing no drug were incubated at 37 degrees C for 24 hours under shaking (8 cm-moving range and 56 strokes per minute). After incubation, the medium was diluted by a 0.1% Tween 80 aqueous solution to 10(-7), and each 0.02 ml-sample of 10(-4) to 10(-7) suspensions was inoculated onto Ogawa egg medium. The Ogawa egg medium slants were incubated at 37 degrees C for 28 days, and the number of colonies was counted. The bactericidal activity was determined as a ratio of the number of colony-forming units in 10 ml-aliquot of drug-containing Dubos liquid medium against the number of colony-forming units in the control Dubos liquid medium. The results are shown in Figures 1 and 2. Under the condition tested, rifampicin, isoniazid, ethambutol, ethionamide and cycloserine did not exhibit any bactericidal activity, and only streptomycin and enviomycin exhibited bactericidal activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313967 TI - [Proceedings of the 65th meeting of the Japanese Society for Tuberculosis. Tokyo, 27-28 March 1990. Abstracts]. PMID- 2313969 TI - Guide to lobbying. PMID- 2313968 TI - AIDS education: teaching isn't just in the classroom anymore. PMID- 2313970 TI - The pathophysiology of AIDS. PMID- 2313971 TI - Preparing the person with AIDS for discharge: a nursing directive. PMID- 2313972 TI - Women and children and HIV infection. PMID- 2313973 TI - What is a raid and its effect on nursing representation by non-nurse unions? PMID- 2313974 TI - Analysis of albumin charge by direct immunofixation in ultrathin gels. PMID- 2313975 TI - Excess parathyroid hormone adversely affects lipid metabolism in chronic renal failure. AB - Hyperlipidemia is common in chronic renal failure (CRF), but the underlying mechanisms are not clearly defined. Certain data points toward a potential role for the state of secondary hyperparathyroidism of CRF in its pathogenesis. We examined the effects of parathyroid hormone (PTH) on lipid metabolism utilizing intravenous fat tolerance test (IVFTT) and post-heparin lipolytic activity in five normal dogs, in six animals with CRF and secondary hyperparathyroidism (NPX) and in six normocalcemic-thyroparathyroidectomized dogs (NPX-PTX) with comparable degree and duration of CRF. NPX dogs had fasting hypertriglyceridemia (82 + 6.0 mg/dl vs. 49 +/- 2.7 mg/dl in normal dogs, P less than 0.01), abnormal IVFTT, and reduced post-heparin plasma LPL activity (151 +/- 10 vs. 275 +/- 15 mumol fatty acids/ml/min in normal dogs, P less than 0.01). The NPX-PTX dogs had normal fasting levels of serum triglycerides (42 +/- 0.6 mg/dl), normal IVFTT, and normal post-heparin plasma LPL (317 +/- 19 mumol fatty acids/ml/min) despite CRF. Post-heparin HL activity in plasma was not different between NPX and NPX-TPX dogs. The results show that excess blood levels of PTH and not other consequences of CRF are mainly responsible for the abnormalities in lipid metabolism. The data are consistent with the notion that excess PTH reduces post-heparin LPL activity in plasma, which in turn results in impaired lipid removal from the circulation and consequently hyperlipidemia. PMID- 2313976 TI - A study of growth regulators of renal cortical tubular cells in the rabbit liver. AB - Two growth regulators, a growth stimulator for cultured renal tubular cells and a growth inhibitor, were observed in this study in rabbit liver homogenate after a unilateral nephrectomy. These regulators appeared in the liver on the third day after this nephrectomy, decreased on the seventh day, and disappeared by the fourteenth day. The growth stimulatory activity, termed a tubular cell growth factor (TuCGF), was a heat- and acid stable 15 to 20 KDa protein. The additive effects of TuCGF on the epidermal growth factor (EGF), the insulin-like growth factor-I (IGF-I), and the fibroblast growth factor (FGF) were observed; the results suggest that TuCGF differs from EGF, IGF-I, or FGF. In contrast, the growth inhibitory activity, termed a tubular cell growth inhibitor (TuCGI), was a heat- and acid-labile protein with a molecular weight of about 150 to 200 KDa. This factor potently inhibited the DNA synthesis of tubular cells in the presence of insulin and EGF. These results suggest that TuCGI is not identical with transforming growth factor-beta (TGF-beta). The regulation of these activities by target cell density is also discussed. PMID- 2313977 TI - Renal injury of diet-induced hypercholesterolemia in rats. AB - Abnormalities in lipid metabolism frequently accompany renal disease and may be important in the pathogenesis of progressive renal injury. In the present study, the effects of a high cholesterol diet on renal histology, cortical lipids, and glomerular hemodynamic function were examined in normal rats with and without reduced renal mass. Cholesterol feeding for 19 weeks increased serum cholesterol from 66 +/- 10 mg/dl to 256 +/- 93 mg/dl in two-kidney rats, and from 73 +/- 15 mg/dl to 407 +/- 274 mg/dl in nephrectomy rats (P less than 0.01). Both sham operated and unilateral nephrectomy rats fed a high cholesterol diet had a greater amount of glomerulosclerosis and tubulointerstitial damage than rats fed standard chow. Cortical cholesteryl esters were increased by the cholesterol diet, and correlated with the amount of glomerulosclerosis (r = 0.90, P less than 0.01) and tubulointerstitial injury (r = 0.64, P less than 0.05). Cholesterol feeding and nephrectomy both caused alterations in tissue essential fatty acids, and a panel of specific monoclonal antibodies indicated that renal injury and cortical lipid alterations were associated with an increase in glomerular macrophages. Finally, micropuncture experiments carried out in a separate group of rats fed high cholesterol for 8 to 10 weeks demonstrated increases in glomerular capillary pressure. These results suggest that additional investigations may ultimately determine how cholesterol deposition, altered fatty acid metabolism, macrophages, and increased glomerular pressure might combine to cause chronic progressive renal injury. PMID- 2313979 TI - Glucocorticoid-induced polycystic kidney disease--a threshold trait. AB - Administration of hydrocortisone acetate (250 mg/kg) to newborn mice caused polycystic kidney disease (PKD) of varying proportions in each of 18 different inbred strains; none of the injected controls were affected. All kidneys were histologically examined and scored for degree of cyst formation using a semi continuous (0 to 4+) grading scheme. Results suggested that this condition is a multifactorial threshold trait. For each strain, estimates of the mean and standard deviation of normally distributed liability were determined by maximum likelihood methods. Concomitant analyses showed: 1) a significant environmental effect related to drug source; 2) a variation in thresholds ranging from 0.94 (N = 46) for the B10.M strain to -0.71 (N = 297) for the C57B1/6J strain; and 3) three groups of strains with different susceptibility to PKD. These results are consistent with a multifactorial basis for susceptibility to PKD. Quantitative analysis of thresholds and liability distributions reveals that genetic, environmental and random elements all contribute to the expression and extent of the cystic trait. PMID- 2313978 TI - Role of dialysable solutes in the mediation of uremic encephalopathy in the rat. AB - This study addresses mechanisms of the clinical, encephalopathic uremic illness and its suppression by dialysis. Renoprival rats were treated with peritoneal dialysis (8 exchanges per day, 30 min dwell), or untreated (attrition group), and their EEG's were automatically sampled overnight and subjected to power spectrum analysis as an index of encephalopathy. As in man the background rhythm of the quantified EEG (Q.EEG) in the attrition group slowed with time as extracellular fluid composition became increasingly abnormal; these changes were normalized by therapeutic dialysis (TD) using standard, commercial dialysate. However, Q.EEG slowing was only partially normalized by solute-specific dialysis using "mock uremic dialysate" (M-UD), prepared from laboratory chemicals to equal plasma concentrations in preterminal uremic rats of urea, creatinine, potassium, phosphorus, calcium, magnesium, bicarbonate, sodium, and chloride. When only phosphate was added to TD, the Q.EEG slowed to the same level achieved after M UD. We conclude that uremic encephalopathy in this model is produced by an unknown neurotoxin and augmented by one or more of the M-UD solutes, phosphate being a likely candidate. To localize the encephalopathic effect, regional brain glucose uptake was estimated in 20 discrete brain areas. Significance of reduced uptake in three areas is discussed. PMID- 2313980 TI - Studies of renal autoregulation in pancreatectomized and streptozotocin diabetic rats. AB - We studied renal autoregulation in pancreatectomized Munich-Wistar diabetic rats and in their sham-operated controls. In a second experiment we studied renal autoregulation in untreated and insulin treated streptozotocin diabetic Munich Wistar rats and their nondiabetic controls. In the first experiment the diabetic rats had higher baseline renal blood flows (RBF). There was a fall in renal vascular resistance (RVR) and sustained RBF in both diabetic and control rats as renal perfusion pressures (RPP) was reduced from 130 and 110 mm Hg. As RPP was reduced from 110 and 80 mm Hg, there was no significant Change in RVR in control rats and RBF began to fall. Below RPP of 80 mm Hg RVR rose and RBF fell sharply in these rats. In contrast, there was a progressive fall in RVR as RPP was lowered to 60 mm Hg in the diabetic rats and, thus, RBF was much better sustained in these animals. In the second experiment the plasma glucose level was 502 +/- 52 mg/dl (X +/- SD) in the untreated diabetic rats and only modestly reduced to 411 +/- 49 mg/dl in the insulin treated animals. Untreated streptozotocin diabetic rats had moderately reduced and insulin-treated diabetic rats had mildly reduced baseline RVR and RBF. However, in these animals as in the pancreatectomized rats the increases in RVR noted in control rats at subautoregulatory RPPs were not seen. Thus, regardless of whether baseline RBFs were increased or decreased, diabetic rats sustained RBF at markedly reduced RPPs far more efficiently than did nondiabetic rats. The pathogenesis of these abnormalities in diabetic rats was not learned in these studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313981 TI - Ticlopidine prevents renal disease progression in rats with reduced renal mass. AB - Functional and morphological studies were done in three groups of male Sprague Dawley rats after removal of the right kidney and infarction of approximately five-sixths of the left. Group 1 received no specific therapy. Group 2 was treated with ticlopidine, 150 mg/kg per os, for 50 days starting 10 days after surgical ablation. Group 3 was given the thromboxane antagonist, GR 32191, 3 mg/kg b.i.d. orally for 50 days, like ticlopidine. Untreated Group 1 rats developed renal insufficiency, systemic hypertension, progressive proteinuria and glomerulosclerosis. In Group 2 treatment with ticlopidine was associated with less severe impairment of renal function. Proteinuria was significantly lower and animals were partially protected from the development of glomerulosclerosis. These animals had significantly prolonged skin bleeding time. In vitro ADP and arachidonic acid (AA)-induced platelet aggregation was inhibited. Systemic blood pressure was significantly lower than in controls. In Group 3 rats GR 32191 failed to influence progressive proteinuria and severity of glomerulosclerosis which were comparable to those in Group 1. Bleeding time was not prolonged, and in vitro platelet aggregation was inhibited only when AA was used as aggregating agent. Systemic blood pressure was not influenced. These studies suggest that a drug like ticlopidine, which has a broad spectrum of pharmacological actions on platelets and platelet-cell interactions, does retard the development of progressive renal injury when nephron number is reduced. Specific blocking of thromboxane A2 (TxA2) biological activity does not influence progressive renal disease in rats with remnant kidney. PMID- 2313983 TI - Chromogranin A in uremia: progressive retention of immunoreactive fragments. AB - Chromogranin A is a soluble protein that is stored and released with catecholamines from their secretory vesicles. Its measurement is a probe of exocytotic sympathoadrenal activity, and in plasma it may also be a useful tool in the diagnosis of peptide producing endocrine neoplasms. Because we have found that chromogranin A is elevated in secondary (uremic) hyperparathyroidism, we systematically investigated the influence of renal dysfunction and its attendant hyperparathyroidism on chromogranin A in several subject groups: normal controls (serum creatinine less than or equal to 1.2 mg/dl), nonazotemic renal transplant recipients, nonazotemic subjects with glomerular disease (serum creatinine between 1.2 and 2 mg/dl), mid-range renal disease subjects (serum creatinine between 2 and 7.5 mg/dl), and end-stage renal disease subjects (serum creatinine greater than 7.5 mg/dl). Plasma chromogranin A rose with deterioration of renal function, and the rise was independent of etiologic diagnosis, blood pressure, or indices of sympathoadrenal activity or hyperparathyroidism. Size fractionation of uremic plasma by gel filtration, and immunoextraction by region-specific anti chromogranin A (anti-N-terminal, anti-C-terminal, and anti-mid-molecule) antibodies suggested that chromogranin A immunoreactivity circulates in uremia as lower molecular weight fragments of the parent chromogranin A molecule, with mid molecule fragments the major constituent. This immunoreactivity is only minimally removed by peritoneal dialysis and is not at all hemodialyzable. The uremia-dose dependent accumulation of chromogranin A immunoreactive fragments in renal failure suggests that the kidney is a major site of disposition or removal of the immunoreactivity. Furthermore, lack of detectable chromogranin A immunoreactivity in normal subjects' urine suggests that the immunoreactivity is destroyed as it is removed by the kidney. We conclude that plasma chromogranin A increases in proportion to degree of renal insufficiency and that renal function must therefore be controlled when using plasma chromogranin A in the investigation of amine or peptide hormone storage and release. PMID- 2313982 TI - Efficacy of hepatic computed tomography to detect iron overload in chronic hemodialysis. AB - The diagnostic efficacy of hepatic computed tomography density (HCTD) in comparison with serum ferritin for the detection of iron overload was investigated in uremic patients on maintenance hemodialysis (HD) and in patients with idiopathic hemochromatosis (IHC). Ten IHC patients, 38 HD patients and 40 healthy subjects underwent the CT scanning of the liver and determination of percent saturation of transferrin, serum ferritin concentration and HLA typing. Liver iron content was determined by histochemical grading and direct measurement of liver iron concentration either in IHC patients or in HD patients. Nineteen HD patients were considered to have iron overload on the basis of liver iron concentration exceeding 3.6 mumol/100 mg dry weight. The mean +/- SD values of HCTD in healthy subjects, IHC patients, HD patients with iron overload and without iron overload were 60.2 +/- 5.6, 79 +/- 5.6, 71.4 +/- 3.6, 58 +/- 3.8 Hounsfield units, respectively. HCTD showed positive correlations with liver iron concentration and serum ferritin either in IHC patients or in HD patients. The analysis of the diagnostic efficacy of HCTD in comparison with serum ferritin for the detection of excessive hepatic iron in HD patients demonstrated that HCTD had higher sensitivity, specificity, positive and negative predictive values. Cut-off points were arbitrarily fixed to 66 Hounsfield units for HCTD, 400 micrograms/liter for serum ferritin and 3.6 mumol/100 mg dry weight for liver iron concentration. Seventeen HD patients who possessed the histocompatibility antigens associated with IHC, namely HLA-A3 and/or HLA-B7 and/or HLA-B14, had liver iron concentration, serum ferritin and HCTD values higher than those of the HD patients without these "hemochromatosis alleles".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2313984 TI - Kinetics of peritoneal protein loss during CAPD: I. Different characteristics for low and high molecular weight proteins. AB - We studied the peritoneal protein loss in 13 patients during CAPD using 2 liters of 1.5% dextrose dialysis solutions. We compared the kinetic characteristics of the peritoneal mass transfer and clearance of proteins over a wide range of molecular size, to those of small molecular weight solutes. The peritoneal clearance of all studied proteins and solutes correlated strongly and negatively with their molecular mass. No changes were observed in these clearances during 58 months of dialysis. Unlike the peritoneal mass transfer and clearance of small molecular weight solutes (less than 200) which revealed a remarkable progressive drop after the first hour of an eight-hour dialysis cycle, the mass transfer and clearance of proteins of large molecular weight (greater than 68,000) was continuous throughout the eight hours. The clearance of proteins of small molecular weight (less than 15,000) showed similar kinetics to small solutes (less than 200). These results indicate that long dwell times (6 or 8 hr) of peritoneal dialysis are detrimental for the loss of large molecular weight proteins (such as albumin and immunoglobulins) in view of the negligible dialysance of both small solutes (creatinine and potassium) and "intermediate molecules" (represented by the small molecular weight proteins) during the latter hours of long dwell cycles. Thus we suggest that substituting CAPD (3 x 8 hr or 4 x 6 hr) with CCPD (6 x 1 hr) may limit protein loss in these patients. PMID- 2313985 TI - Kinetics of peritoneal protein loss during CAPD: II. Lipoprotein leakage and its impact on plasma lipid levels. AB - We quantified the plasma levels and peritoneal loss of lipids and lipoproteins, and studied the composition of plasma and effluent lipoproteins in 16 patients on CAPD (5 females and 11 males, 18 to 76 years old). Five patients were studied prospectively (at 0, 1, 3 and 6 months) and 11 patients at 6 to 58 months on CAPD (N = 30). Elevated levels of plasma VLDL and reduced levels of plasma HDL were maintained in these patients throughout 58 months of CAPD, whereas the initially increased LDL levels showed a tendency towards normalization. All plasma lipoproteins (VLDL, IDL, LDL and HDL) were present in the peritoneal effluent. The lipoproteins isolated from plasma and peritoneal fluid shared a similar lipid and apolipoprotein composition. The peritoneal transport characteristics of plasma lipoproteins were similar to other plasma macromolecules. Their clearance correlated with their molecular mass, plasma concentration and dwell time, but was not affected by duration of CAPD treatment. The plasma lipid and lipoprotein levels were unaffected by the rate of glucose absorption. The peritoneal protein clearance correlated positively with plasma levels of triglyceride and LDL, and negatively with plasma HDL. An inverse correlation was observed also between plasma levels of HDL and its peritoneal clearance (r = -0.393, P less than 0.025, N = 30). The continuous peritoneal loss of HDL and the hypertriglyceridemia were found to contribute most to the persistent low plasma levels of HDL in CAPD patients, and thus may lead to the accelerated atherosclerosis observed in these patients. PMID- 2313987 TI - [Retinal diseases as a cause of increased latency in the visual evoked cortical potential]. AB - Retinal and cortical potentials to reversing checkerboard stimuli (P-ERG, P-VECP) were recorded simultaneously in ten patients with disease of the central retina and eleven patients with tumor-related optic nerve changes. While both groups exhibited comparable P100 delays in the P-VECP, delays of the q component in the P-ERG were only observed in the group with retinal disease. Thus, measurement of P-ERG and P-VECP latencies enables retinal to be distinguished from post-retinal disease in cases with visual disturbances where there are no obvious fundus changes. PMID- 2313986 TI - [Changes in the circulation of the eye caused by Vorosmarthy preoperative ocular pressure]. AB - Prior to, directly after and 15 minutes after preoperative Vorosmarthy oculopression (30, 40, or 50 mm Hg; 15 min), 30 patients were examined by oculooscillodynamography after Ulrich. Systolic retinal and ciliary perfusion pressures were higher directly after oculopression, whereas the systolic and diastolic ocular blood pressures (intramural pressures) were lower. These changes did not depend significantly on the level of oculopression. Fifteen minutes after oculopression, the ocular perfusion and blood pressures were largely normalized. The hemodynamic changes observed reflect the decrease in intraocular pressure resulting from oculopression. The changes are thought to have a beneficial effect on ocular perfusion (reduction in tissue pressure, decrease in vascular resistance, increase in transmural pressure). The authors' results are consistent with the finding in animal experiments that blood flow to the retina, optic nerve, and uvea increases for a short time after oculopression (Jay et al., Acta Ophthalmol. 1986). PMID- 2313988 TI - [Early diagnosis of congenital disorders of color vision with the Velhagen "Pflugerhaken Color Charts for evaluating color perception" in 3,375 preschool children]. AB - In three series of examinations, 3375 male preschool-age children and 93 adult normal trichromates were tested using the Velhagen Pflugerhaken charts. The authors recommend modifying the evaluation of the results slightly by introducing a "doubteful" category for children who make one mistake or who show hesitation and lack of assurance in interpreting the charts. Using this modified form of assessment, diagnoses of "probably achromatopic" and "doubtful" were made in 7.16% and 2.13% respectively of 1689 preschool-age boys. The failure rate during the test and the duration of the examination were age-dependent, and declined with increasing age from 4.15% to 0.45% and from 1.18 min to 0.59 min, respectively. Most mistakes were made with charts nos. 9, 3, and 5. The results of tests with Pflugerhaken charts are fully comparable with those of other internationally used tests for adults. They can be recommended for screening preschool-age children. PMID- 2313989 TI - [Local anesthetics in the aqueous humor in local anesthesia of the eye]. AB - Local anesthetics injected retrobulbarly are detectable in the aqueous humor. From 40 patients who received a total dose of 140 mg lidocaine, 15 mg bupivacaine, and 30 mg etidocaine, samples of aqueous humor were taken between 30 and 90 minutes after administration (average 57 minutes). The mean lidocaine concentration was 1.02 micrograms/ml, that of bupivacaine 0.075 micrograms/ml. Etidocaine, used only for facial nerve block in front of the ear, could not be detected in the aqueous humor. All three substances were found in the central venous blood. It therefore appears unlikely that any of them are transported via the blood-aqueous barrier, whether actively or passively. Local anesthetics can inhibit corneal cell proliferation and result in lens opacification when administered into the conjunctival sac. It may be that local anesthetics detected in the aqueous humor have similar effects resulting from contact with the cornea and lens. PMID- 2313990 TI - [Spot-like to reticular pigment displacement in a patient with pseudoxanthoma elasticum (Gronblad-Strandberg syndrome)]. AB - The authors report a rare observation of leopard spot-like and reticular pigmentary patterns in a patient with pseudoxanthoma elasticum (PXE). Characteristic fundus changes associated with PXE have been described as angioid streaks, subretinal neovascularization membranes, peau d'orange, focal retinal pigment epithelium atrophy (salmon spots), drusen, and optic nerve head drusen. The new manifestation of PXE in the fundus of the patient described here is a random scattering of small, dark brown pigment dots throughout the macula and around the disk. These clumps may flow into one another or join together like a string of pearls. These changes are rare and should be distinguished from the others mentioned above. To the authors' knowledge no more than ten cases have been reported in the literature so far. PMID- 2313991 TI - [Congenital lacrimal duct obstructions]. AB - If typical congenital nasolacrimal obstruction symptoms occur during the first few days of life immediate treatment is necessary. At the latest within two weeks the benefits of medication and massages of the lacrimal sac should be exploited to treat these conditions. It should be pointed out in particular that persisting membranes may perforate spontaneously. Should this treatment fail, high-pressure syringing and probing with Bangerter probes under local anesthesia must be performed very early. Due to the fact that the less complicated high-pressure syringing is often unsuccessful it is followed without delay by probing. If the ophthalmic surgeon is skilled, proceeds with care, and observes certain technical details complications can be avoided. The treatment described only fails in exceptional cases. PMID- 2313992 TI - [Combination hydrophilic contact lenses in keratitis neuroparalytica]. AB - A 23-year-old patient with neuroparalytic keratitis uses an extended-wear lens to correct his myopia and a larger bandage lens over it. This combination has proved superior to single-lens therapy and has eliminated painful symptoms. PMID- 2313993 TI - [Plexiglass replicas for optimizing selection and site of ruthenium 106 applicators]. AB - Contact irradiation of choroidal tumors using Ruthenium106 applicators has become a well-established treatment modality. In order to destroy all tumor tissue while at the same time sparing the neighboring structures of the eye a plaque has to be placed exactly, just overlapping the tumor's base. With transparent plastic replicas with a dark-colored rim and adequate diaphanoscopy this can be accomplished with an otherwise unattainable degree of precision, while at the same time reducing the radiation dose sustained by the surgeon. The design of the replicas and the localization technique are described in detail. PMID- 2313994 TI - [Diffractive multifocal intraocular lenses. A prospective clinical study]. AB - Forty-three patients were examined three months after implantation of a multifocal or bifocal intraocular lens following cataract extraction. With far vision correction, simultaneous bifocal function with far acuity better than 0.5 and near acuity better than Nieden 3 was achieved in 95.4% of these cases. Glare sensitivity was tested with the BAT and mesopic visual acuity was examined with the Ocutrast. No statistical differences were found between these patients and a control group with monofocal IOLs. PMID- 2313995 TI - [The TV head ophthalmoscope for videodocumentation of fundus changes]. AB - The present paper describes the TV head ophthalmoscope, a logical further development in indirect ophthalmoscopy. It comprises a modern indirect binocular head ophthalmoscope and a micro-CCD color camera. The instrument enables all structures on the fundus to be observed as far as the periphery. Objects seen dynamically include detached retina and vitreous membranes. Practical fields of application are retinal detachment surgery and for demonstration and training in indirect ophthalmoscopy. PMID- 2313996 TI - [Possibilities for reproducing stereoscopic images on monitors in relation to the surgical microscope]. AB - A variety of systems, including open-sight systems, can be used in combination with an operating microscope to reproduce stereoscopic images on a monitor. All these systems have the disadvantage that they disturb the free interplay of accommodation and convergence, and in the long term this can be tiring for the observer. A method similar to holography might be an ideal open-sight method for imaging the surgical procedure three-dimensionally. PMID- 2313997 TI - [The regression behavior of choroid melanoma following radiotherapy--a new prognostic parameter?]. AB - The present paper reports on follow-up examinations of 246 patients after Ruthenium106 treatment of choroidal melanomas (follow-up time 1.8 to 13 years). In January 1988, 212 patients were alive and free of metastases; 15 had died, 12 of them of melanoma metastases, and 17 could not be followed up. In a retrospective analysis of factors influencing tumor-related mortality, the rate of regression of irradiated tumors was found to be particularly significant. The mean time taken to reduce tumor volume by half was 4.4 months in patients who died of metastases, as against 6.6 months in a matched group of survivors. Using discriminance analysis, the difference was found to be highly significant (P = 0.0058). In the total patient population, a significant correlation was found between pretreatment tumor volume and the probability of metastases (P = 0.058). It may be concluded, though with the qualification that the number of tumor related deaths was small, that the tumor regression rate is an important factor in the prognosis for patients with Ruthenium-treated malignant choroidal melanomas. PMID- 2313998 TI - [Delayed fontanelle closure in infants with cyanotic cardiomyopathies]. AB - In comparison with infants not suffering from cyanotic heart failures a different size (width and length) as well as a delayed time of closure of the anterior fontanelle in infants with congenital cyanotic heart failures were detected. In these patients typical phenomenons by ultrasound examinations are described also. PMID- 2313999 TI - [Intracranial arterial aneurysm in children]. AB - Over a period of 13 years 5 children aged 8 to 11 were operated on intracranial arterial aneurysms. Special features of these aneurysms in children were accidents in the anamnesis of three children and one localization at the internal carotid artery bifurcation and another one at a peripheral artery. It is unusual to have fusiform dilatations at the basis of two aneurysms and one large aneurysm among 5 cases in comparison to aneurysms in adults. This hints to the possibility of more extended artery lesions with aneurysms in children. The intracranial hemorrhage which often leads to a diagnosis makes an immediate neuroradiological check necessary. Hemorrhage or operation were survived by all children. Space occupying hematomas diminish the quality of outcome considerably and therefore must be operated on immediately. PMID- 2314000 TI - [Esophageal function of infants with sudden infant death--risk]. AB - In 24 patients at risk for SIDS (12 infants with a near miss event and 12 infants with apnea and perioral cyanosis during sleep) respiratory and esophageal function were investigated by impedance pneumography (IP) and esophageal manometry combined with simultaneous pH-monitoring (EMPH). Both groups had ad early pathologic breathing pattern, but did not show any difference in the recorded parameters (number of apneic spells, longest apneic spell, apneic spells longer than 10 seconds, transcutaneous oxygen pressure, mean apnea time). Near miss infants had about 50% more manometric refluxes (15.4 +/- 1.3) than the apnea/cyanosis group (9.9 +/- 2.2). This difference was mainly caused by a significant rise of reflux episodes without pH-change (near miss 8.5 +/- 3.1 versus 2.9 +/- 1.4 in apnea/cyanosis infants). Furthermore, propulsive peristaltic properties after induced swallows were more disturbed in the near miss group (3.3 +/- 1.0 versus 6.1 +/- 1.9). On the other hand, the apnea cyanosis group showed significantly more pH-drops under 4 (6.8 +/- 2.3 vs 2.4 +/- 0.7), which might be due to a more rapid clearance of neutralising milk from the stomach in these infants. In conclusion the study showed that infants with a near miss event in the anamnesis suffer from a more pathologic esophageal motor function when compared with infants with apneic spells and cyanosis during sleep. Near miss infants are also considered to have a delay of gastric clearance. PMID- 2314001 TI - [Effect of nutritional status on absorption kinetics of vitamin E in mucoviscidosis]. AB - Exocrine pancreatic insufficiency with varying severity must be anticipated in 85 95% of CF patients. It leads to fat maldigestion and malabsorption of the liposoluble vitamins - A, D, E, K - and fecal loss of fat. In general, supplementation with fat-soluble vitamins is recommended in CF patients. In this study an oral vitamin E tolerance test (100 mg/kg bodyweight) was performed in 5 healthy adult volunteers to elaborate a vitamin E absorption kinetics and additionally in CF patients on medication with pancreatic enzymes to evaluate the absorption of vitamin E. 19 CF patients (ages 4 to 19 years) were studied after cessation of any additional vitamin E supplementation for 7 days. Vitamin E serum concentrations were sampled over a 72 hour period. Serum vitamin E determinations were performed with a HPLC-fluorescence technique. The kinetics of Vitamin E in healthy volunteers can be described with an open 2 compartment model. CF patients revealed consistently an altered kinetics of absorption of vitamin E, which was not compatible with this model. Baseline (c*) and maximal serum concentrations (cmax) of vitamin E as well as the area outer the oral absorption curve (AUC) correlated with the nutritional status expressed by bodyweight percentiles in CF patients. The results of this study show that in normal weight CF patients on pancreatic enzymes medication vitamin E depletion is unlikely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314002 TI - [Endocardial fibroelastosis of the left ventricle in a patient with Alagille syndrome]. AB - We present a case of a 6 week old infant with Alagille syndrome. Cardiological evaluation revealed peripheral pulmonary arterial stenosis and left ventricular endocardial fibroelastosis. While peripheral pulmonary arterial stenosis are typical for the syndrome this is the first case reported with endocardial fibroelastosis. Complex cardiac malformations may worsen the prognosis in Alagille syndrome. They require early diagnosis and therapy. PMID- 2314003 TI - [Catel-Manzke syndrome]. AB - The leading symptom of Catel-Manzke syndrome is a characteristic deviation of index fingers. Further the patients suffer from symptoms of Pierre-Robin syndrome (micrognathia, glossoptosis, cleft palate). The survival of patients, mostly male, depends on the severeness of congenital malformation of the face skull. The rare disease is demonstrated and discussed by two own cases. PMID- 2314004 TI - Cyclosporin reduces renal blood flow through vasoconstriction of arcuate arteries in the hydronephrotic rat model. AB - Besides its beneficial effects in organ transplantation cyclosporin (CyA) exhibits nephrotoxic (and other) side effects. CyA nephrotoxicity is associated with a decrease in glomerular filtration rate. Two mechanisms of action have emerged. First, tubular destruction with secondary reduction in renal blood flow and glomerular filtration rate; second, decrease in renal blood flow with secondary interstitial fibrosis. We studied the effect of an acute infusion of CyA in the hydronephrotic rat kidney model, which lacks tubular structures completely. Hence, only the direct vascular effects of CyA were determined. Five groups (G) of rats were studied by television microscopy. G I (n = 7) received CyA (30 mg/kg, i.v.) dissolved in cremophore/plasma; G II (n = 5), time control 1, received cremophore/plasma instead of CyA; G III (n = 8), received CyA 30 mg/kg followed by 20 mg/kg CyA i.v. dissolved in an ethanol/tween solution; G IV (n = 3), time control 2 received ethanol/tween alone in the experimental period; in G V, CyA was applied locally onto the surface of the kidney with concentrations increasing from 10(-7) to 10(-5) M. CyA caused profound reduction in the diameter of arcuate arteries in groups I and III, in contrast to the time control groups II and IV. The vasoconstriction could be partially reversed by the calcium-channel blocker nitrendipine, and completely reversed with acetyl choline. Glomerular blood flow decreased due to CyA and could not be completely normalized by either drug. Increasing the dosage from 30 to 50 mg/kg was not associated with further reduction in blood flow. Local application of CyA (G V) did not demonstrate vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314006 TI - Vitamin B6 status in uremia. AB - We have studied vitamin B6 status in 26 uremic patients, 18 on maintenance hemodialysis and 8 nonhemodialyzed. The vitamin B6 status was estimated by an assay of erythrocyte aspartate aminotransferase and coenzyme stimulation. Hemodialyzed uremic patients were found to have vitamin B6 deficiency. Patients were treated with 150 mg pyridoxine hydrochloride daily for 4 weeks. Erythrocyte aspartate aminotransferase increased significantly in both groups of uremic patients, the increase being greater in hemodialyzed patients. In vitro pyridoxal phosphate stimulation produces an erythrocyte aspartate aminotransferase activity greater than that obtained before pyridoxine hydrochloride administration. After cessation of pyridoxine hydrochloride treatment, erythrocyte aspartate aminotransferase decreases in hemodialyzed patients, while it remains elevated in nonhemodialyzed patients. The data obtained appear to indicate that vitamin B6 administration to patients with chronic renal insufficiency must be appraised not only for correcting the deficit but also for increasing the intracellular pyridoxal phosphate concentration, which could modify the possible functional impairment at the level of apoenzymes that use pyridoxal phosphate. PMID- 2314005 TI - Ammonium and bicarbonate homeostasis in chronic liver disease. AB - Whereas traditionally in acid-base physiology one considers just two organs (lungs and kidneys) to be involved in the regulation of systemic acid-base homeostasis, recent developments indicate that also the liver must be viewed as an important organ for pH regulation. This is because urea synthesis is a quantitatively important bicarbonate-consuming process, which in turn underlies a feedback control by the acid-base status at least in vitro. Consequently, renal ammoniagenesis, generally accepted to be a direct bicarbonate-generating process, can be viewed as a pH-controlled ammonium homeostatic response. In view of the controversies regarding the roles of ureogenesis and renal ammoniagenesis in acid base regulation, their relationships were studied in 28 patients with normal renal functions, but varying degrees of a well-compensated chronic liver disease. Progressive loss of urea cycle capacity (as determined by in vitro incubations of human liver tissue) was parallelled by increasing in vivo plasma bicarbonate levels (and metabolic alkalosis) and an increasing NH4+ excretion into the urine. Accordingly, renal ammoniagenesis rose with the extent of metabolic alkalosis. Neither hypokalemia, hyperaldosteronism, diuretic treatment, or volume contraction were present, and a satisfactory explanation for this unusual behavior of renal ammoniagenesis in terms of traditional acid-base physiology cannot be given. Here, it seems that renal ammoniagenesis is governed rather by the need to eliminate ammonia than by the acid-base status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314008 TI - Skin surface oxygen pressure fields during administration of prostaglandin E1 in patients with arterial occlusive disease. AB - Prostaglandin E1 is offered as a new therapeutic agent in the treatment of severe peripheral arterial occlusive disease. Especially when treating patients with ulcers or gangrene, the oxygen tension of the skin should improve during PGE1 administration. The new technique of assessing skin surface oxygen pressure histograms allows study of the skin microcirculation in vivo. Oxygen histograms were determined on the forefeet of 19 patients with different degrees of disease and different occlusion levels before and during a single intraarterial infusion of PGE1 at a dosage of 1.5 ng/kg body weight/min. Only 9 patients showed improvement during the infusion period. Skin oxygen pressure was increased to a large extent only in patients assumed to suffer from diabetic microangiopathy. The effect of a long-term therapy with PGE1 on skin microcirculation remains to be settled. PMID- 2314009 TI - Value of urinary neopterin in the differential diagnosis of bacterial and viral infections. AB - Neopterin is released by stimulated macrophages. In this study we analyzed the diagnostic potential of urinary neopterin concentrations in patients with bacterial and viral infection. All but one of 17 patients with viral infection had increased urinary neopterin concentrations. Patients with bacterial urinary tract infection also showed increased neopterin concentrations, whereas patients with bacterial pneumonia had significantly lower neopterin levels. In addition, patients with acute bacterial pneumonia had lower neopterin levels than patients with protracted infection. A significant inverse correlation between urinary neopterin and hemoglobin concentrations was found. Neopterin concentrations could serve as a helpful additional marker of infectious diseases. Combined with other clinical and laboratory parameters it is a useful parameter for distinguishing between viral and bacterial origins of infection, as was shown by multivariate stepwise linear discriminant analysis. PMID- 2314007 TI - [Central pontine myelinolysis following severe hyponatremia]. AB - Central pontine myelinolysis is a process of demyelinisation with variable neurological symptoms related to the localization. Predisposing factors are alcoholism and malnutrition. Rapid correction of severe hyponatremia is suspected to be a primary cause for central pontine myelinolysis. We report a 43 year old chronic alcoholic and polytoxicomanic female patient, who was admitted comatose with a serum sodium level of 94 mmol/l, caused by a syndrome of inappropriate ADH secretion. After initial improvement under careful sodium correction, the patients neurologic condition degraded progressively and within 4 weeks she developed a "locked-in"-syndrome. Only then the suspected central pontine myelinolysis could be demonstrated in nuclear magnetic resonance and computer tomography. We presume that, although sodium correction was done relatively slowly in this patient, it probably contributed to her development of central pontine myelinolysis all the same. Due to this case we review the literature on correction of hyponatremia, which shows growing evidence that it should start early but be continued very slowly (rise in serum-Na: max. 0.6 mmol/l/h) and requires frequent laboratory controls. PMID- 2314011 TI - [WHO workshop: management in nursing]. PMID- 2314010 TI - Postischemic diagnostic localization of tubular lesions. AB - Several functional parameters were applied in an experimental model of ischemia to test the ability to localize the distribution of tubular lesions. Canine kidneys were perfused with protective solutions and rendered ischemic for definite periods. Renal function was determined during a subsequent 3-h reperfusion. The pattern and the extent of renal injury were influenced by varying the duration of ischemia and by modifying the protective solution used. The results suggest that by employing an appropriate selection of parameters it is possible to allocate renal injury to definite sections of the tubules. According to such an evaluation, under protection with HTK-solution, the proximal tubule limits the tolerance of renal ischemia. The thick ascending limb shows some vulnerability that is aggravated by disadvantageous modifications of the protective solution and that may become more pronounced in the course of reperfusion. In contrast, more distal parts of the nephron retain a remarkable reserve transport capacity after a tolerable level of ischemia. PMID- 2314012 TI - [Solution of the test on knowledge of AIDS (in 12/89). Did you know it?]. PMID- 2314013 TI - [The shining of the Lighthouse in Basle]. PMID- 2314014 TI - [Useful also for nursing personnel: the person-centered discussion. Helping with empathic dialogs]. PMID- 2314016 TI - [Physicians and nurses meet together. Cooperation--but how?]. PMID- 2314015 TI - [Blood transfusion from the viewpoint of anesthesia]. PMID- 2314017 TI - [Revision of educational regulations for the nursing professions. Position of the Swiss Nursing Association]. PMID- 2314018 TI - [Verbal silence--severity of illness (1)]. PMID- 2314019 TI - [The caregiver facing the patient in crisis--meeting in order to help]. PMID- 2314020 TI - [Psychiatric research--lifting the veil]. PMID- 2314021 TI - [The quality of life of patients in remission]. PMID- 2314022 TI - [Seminar for the revision of by-laws. Unity in diversity]. PMID- 2314023 TI - [What do you know about AIDS?]. PMID- 2314024 TI - [Varicose veins are not always innocuous]. PMID- 2314025 TI - [Monitoring in anesthesiology. The importance of the stethoscope]. PMID- 2314027 TI - [Common interest groups of nurse anesthetists]. PMID- 2314026 TI - [Development of the role of the nurse-anesthetist]. PMID- 2314028 TI - [Cycle of education for educators. An experience to live through]. PMID- 2314029 TI - [Verbal silence--severity of illness (2)]. PMID- 2314030 TI - [Support for women with mastectomies. "To live as before"]. PMID- 2314031 TI - [To flee or to resist]. PMID- 2314032 TI - ["Disturbed eating behavior--psychologic disorders?"--a diploma thesis. When the crisis grows weighty]. PMID- 2314034 TI - [Practitioners in geriatric nursing. Sandwiched in between what we ought to do and what we are doing]. PMID- 2314033 TI - [The importance of nursing care for the patient with mechanical circulatory assistance]. PMID- 2314035 TI - [How an operating room nurse turned into a sales lady]. PMID- 2314036 TI - [Pathways out of the maze of human repression logic. Repression: protection and blocking]. PMID- 2314037 TI - [Study on the work in homes for the aged and in nursing homes. New personnel policies are absolutely necessary]. PMID- 2314038 TI - [Risk of infection in the work place?]. PMID- 2314039 TI - [Answers to our questionnaire: did you know it?]. PMID- 2314040 TI - [When the patient refuses to eat or drink. Dehydration--must we or must we not interfere?]. PMID- 2314041 TI - [Etiology, clinical aspects and therapy of Alzheimer's disease]. PMID- 2314042 TI - [What is the diagnostic value of electromyography?]. PMID- 2314043 TI - [The importance of acoustically evoked potentials for the diagnosis of hearing loss]. PMID- 2314044 TI - [New trends in the surgical therapy of neck tumors]. PMID- 2314045 TI - [Erythromycin]. PMID- 2314046 TI - [Gyneco-oncologic nursing]. PMID- 2314047 TI - [In search of better analgesics]. PMID- 2314048 TI - [Oncology--chronicle of a disease]. PMID- 2314049 TI - Subacute combined degeneration and induction of ornithine decarboxylase in spinal cords of totally gastrectomized rats. AB - Totally gastrectomized rats have been used to induce a spongy demyelination in the white matter of the spinal cord (SC) which is strongly reminiscent of that observed in subacute combined degeneration of human SC. Totally gastrectomized rats are deprived of intrinsic factor and thereafter become deficient in cobalamin. Morphologically, the spongy demyelination of the white matter of the rat SC, was evident 2 months after total gastrectomy. Biochemically, we investigated the hypothesis that polyamine biosynthesis might be deranged in the rat SC with experimental subacute combined degeneration, since polyamines are well known to be bound to myelin in the mammalian central nervous system. We measured the levels of both the polyamine biosynthetic decarboxylases, L ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase, the key points in the polyamine biosynthetic pathway, in these SC. There was a sharp increase in ODC activity in SC 2 months after total gastrectomy, without significant changes in S-adenosyl-L-methionine decarboxylase activity. The increase in ODC activity seems to be organ-specific and was not due to a proliferation of neuroglial cells. Interestingly enough, the same morphologic and biochemical features found in SC of 2-month-totally-gastrectomized rats were present also in SC of newborn rats, which indeed showed incomplete myelination, vacuolated appearance, and an ODC activity level higher than that of adult SC. Therefore, total gastrectomy seems to induce a type of regression in the SC of totally gastrectomized rats toward neonatal life, at least in terms of the degree of myelination and of ODC activity level. Biochemically, no changes in ODC activity were observed in SC of rats fed a cobalamin-deficient diet for 3 months. Morphologically, only a proliferation of neuroglial cells with a moderate demyelination was observed in SC of these rats maintained on a cobalamin deficient diet for 3 months. PMID- 2314050 TI - Partial dermal regeneration is induced by biodegradable collagen glycosaminoglycan grafts. AB - We have sequentially documented the early morphologic events that result in partial regeneration of the adult guinea pig dermis. This phenomenon occurs when a full-thickness skin wound is grafted with a highly specific collagen glycosaminoglycan (CG) copolymer which has been seeded with autologous dermal and epidermis cells (Yannas IV, Lee E, Orgill DP, Skrabut EM, Murphy GF, Proc Natl Acad Sci USA 86:933-937, 1989). By day 7, ultrastructural analysis disclosed highly organized associations between mononuclear cells and CG fibers involving prominent extension of pseudopod-like processes toward the fiber surface. Spatial organization of cells was not evident in ungrafted wounds. By day 10, more than 50% of the CG grafts had been degraded and extensive neovascularization was observed in various stages of formation. By day 14, dermal fibroblasts in the graft site demonstrated random alignment of long axes, and a minor fraction (less than 10%) exhibited features of myofibroblasts. A majority (greater than 50%) of dermal fibroblasts in ungrafted wounds were identified as myofibroblasts at this time, and their axes were regularly aligned in parallel with the overlying epidermal layer. Scattered CG copolymer fragments were engulfed by macrophages by day 14, and complete dissolution occurred by day 21. Dermal blood vessels formed a discrete, subepidermal plexus oriented parallel to the epidermal plane by days 14 to 17 in grafted wound beds but not in ungrafted ones. Progressive, randomly oriented collagen deposition occurred at graft sites during the 1st year, whereas collagen fibers in ungrafted wounds were aligned in a horizontal plane atypical of a forming scar. By 1 year, the graft sites resembled normal dermis, with well defined dermal papillae, normal anastomosing superficial vasculature, nerve fibers, and random collagen fiber morphology. Wound sites at this juncture resembled a mature scar, with a flattened dermal-epidermal interface; rare and disorganized vessels and nerves; and collagen fibers parallel to the epidermis. This investigation demonstrates the critical importance of highly specific extracellular matrix in induction of dermal morphogenesis. PMID- 2314051 TI - Rat intestinal basement membrane synthesis. Epithelial versus nonepithelial contributions. AB - Mesenchymal-epithelial interactions play an important role during tissue differentiation and morphogenesis. The basement membrane, which separates these compartments, appears to be critical to these interactions by providing a substratum for cell adhesion, promoting cell polarity and the differentiated phenotype. Unlike other epithelia, gut enterocytes adhere to, and migrate along a thin basement membrane as they differentiate along the crypt-villus axis with a turnover rate of 48 to 72 hours (rat). The relative importance of the enterocytes or of the mesenchymal cells of the lamina propria to the maintenance of the basement membrane is unknown. As indirect indicators of basement membrane biosynthesis, we have measured, by filter hybridization with labeled cDNA probes, the relative abundance of mRNAs for laminin and collagen IV chains in enterocyte fractions representing the crypt-villus gradient of differentiation and in cells of the underlying lamina propria. In confirmation of a gradient, mRNA for histone H2B was present as a decreasing gradient from crypt to villus, the crypt fraction containing the mitotically active enterocytes being most enriched for this transcript and, in contrast, the mRNA for beta-actin was present as an increasing gradient from crypt to villus, paralleling the abundance of microvillus core structures. The mRNAs for alpha 1(IV) and alpha 2(IV) collagen and laminin B1 and B2 chains were most abundant in the lamina propria. Little, if any, collagen IV mRNA was detectable in the enterocyte fractions. In contrast, laminin B1 and B2 mRNAs were enriched in crypt enterocytes but the steady-state level of these transcripts decreased in the superficial villus enterocyte fractions. These data suggest that the components of the intestinal basement membrane are synthesized by both mesenchymal and entodermal-derived cells. Alterations in the intestinal basement membrane structure and in cell adhesion during enterocyte differentiation may be partly mediated by changes in laminin synthesis by the enterocyte. PMID- 2314052 TI - Effects of systemic complement activation and neutrophil-mediated pulmonary injury on the retention and metastasis of circulating cancer cells in mouse lungs. AB - Vascular pathways are major transit routes for the dissemination of malignant neoplasms and are also regulators of cancer metastasis, in part because the endothelium and vascular basement membrane are barriers to the entry and exit of tumor cells. In this study, we have examined the hypothesis that host cell mediated damage to the pulmonary microvasculature facilitates the experimental metastasis of a syngeneic fibrosarcoma in the C57BL/6J mouse. Intravenous injection of purified cobra venom factor was followed in 30 minutes by complement activation, neutropenia with sequestration of neutrophils in the lung, and increased pulmonary vasopermeability. When syngeneic fibrosarcoma cells were injected simultaneously with cobra venom factor, there was a 3 fold increase in cancer cell retention in the lungs after 24 hours and a 3- to 20-fold increase in metastatic tumor burden after 14 days. Enhanced cancer cell retention after cobra venom factor was not seen in mice deficient in complement component C5 and was diminished by pretreatment of animals with antineutrophil antibodies, catalase, inhibitors of lipoxygenase, thromboxane synthetase, and lipid peroxidation (oxygen radical scavenger). We conclude that neutrophil-mediated microvascular injury can promote the organ localization and metastasis of circulating cancer cells. PMID- 2314053 TI - Effects of propylthiouracil on growth hormone and prolactin messenger ribonucleic acids in the rat pituitary. AB - The effects of hypothyroidism induced by propylthiouracil (PTU) treatment on growth hormone (GH) and prolactin (PRL) messenger ribonucleic acid (mRNA) levels were analyzed in adult female rat adenohypophyses by in situ hybridization histochemistry and Northern hybridization analyses. Twenty-eight days of PTU treatment produced a significant decrease in GH mRNA levels and a smaller decrease in PRL mRNA determined by both in situ hybridization histochemistry and Northern hybridization analyses. A combined procedure of in situ hybridization histochemistry followed by immunochemistry on the same sections revealed mammosomatotropic cells expressing GH mRNA and PRL protein in the same pituitary cells from all treatment groups. Cells expressing GH mRNA and thyroid-stimulating hormone protein were not detected by this method. Immunochemical staining revealed a decrease in GH cells and an increase in thyroid-stimulating hormone cells in hypothyroid rats. Cells expressing both GH and thyroid-stimulating hormone protein were not detected by immunostaining. These results indicate that hypothyroidism produces significant decreases in GH mRNA and also decreases PRL mRNA and that mammosomatotropic cells can be detected in pituitaries from normal and hypothyroid rats. PMID- 2314054 TI - Long-term maintenance of human distal airway epithelial cells in nude mice: a potentially useful model for the study of pulmonary carcinogenesis and lung cell biology. AB - We investigated whether the normal morphology of distal airway epithelial cells from adult human lungs could be maintained for long periods of time as xenografts in nude mice. Peripheral lung tissue obtained from normal regions of lungs resected for lung cancer was transplanted subcutaneously into nude mice. The implants were then retrieved at intervals from 2 to 26 weeks for light and electron microscopy, and for immunohistochemical examination. At 2 weeks, revascularization of the implants and replication of immature epithelial cells were observed. At 4 weeks and thereafter, the epithelium formed in the implants was almost mature and normal in appearance. Pseudostratified columnar epithelium composed of ciliated, mucus, and basal cells lined the larger airspaces, whereas the smaller airspaces including alveolar structures were generally lined with type II pneumocytes and occasionally with Clara cells. Normal alveoli with type I pneumocytes and capillary networks were rarely observed. The implants were maintained in the nude mice for as long as 26 weeks. Cytokinetic studies of the epithelial cells in the implants using immunocytochemical detection of incorporated bromodeoxyuridine revealed that an inverse relationship existed between the degree of maturation and the replicative capacity of the epithelial cells. It was also found that, even in the mature epithelium, a small fraction of the cells were undergoing DNA synthesis. Peripheral lung tissue xenografts in nude mice may provide an excellent in vivo model for the study of pulmonary carcinogenesis and also for the study of both the function and differentiation of human epithelial cells of the distal airways. PMID- 2314055 TI - Testing human hair for drugs of abuse. I. Individual dose and time profiles of morphine and codeine in plasma, saliva, urine, and beard compared to drug-induced effects on pupils and behavior. AB - The time course of appearance of morphine and codeine in beard after single dose administration in two human subjects was monitored by radioimmunoassay and confirmed by gas chromatography/mass spectrometry. Both morphine and codeine appeared in beard approximately 7-8 days after drug administration at a time when drug levels in urine, plasma, and saliva were not detectable and drug-induced effects had disappeared. Drug levels in beard appeared to be dose-related suggesting that hair analysis can provide evidence of time and degree of drug exposure. PMID- 2314056 TI - Comparison of derivatives for determination of codeine and morphine by gas chromatography/mass spectrometry. AB - Pentafluoropropionic anhydride (PFPA) and heptafluorobutyric anhydride (HFBA) derivatives of morphine and codeine demonstrated poor spectra due to low abundances of secondary and tertiary ions. Trifluoroacetamide (MBTFA) has been a widely used derivative; however, the internal standard, nalorphine, displayed very poor stability and this resulted in split peaks by gas chromatography making MBTFA unsuitable for quantitative methods. Quantitation of codeine and morphine using bis-trimethylsilyltrifluoroacetamide (BSTFA/1%TMS) revealed a significant gradual decrease (p less than 0.05) of peak area ratio (PAR) of codeine and morphine compared to the internal standard using selected ion monitoring (SIM). The acetic anhydride derivative showed no significant differences in the peak area ratios for codeine/IS over a period of 24 hours, although the coefficient of variation (CV) was higher for the acetyl derivative than for the TMS derivative of codeine. There was a significant difference associated with the acetyl derivative of morphine at 4 h post derivatization compared to the initial injection (p less than 0.05); however, the acetyl derivative was stable for 24 hours and had a CV of less than 10% at a cutoff of 300 ng/mL. PMID- 2314057 TI - Quantitation and ultraviolet spectrum identification of buflomedil in whole blood and plasma by HPLC. AB - Buflomedil, a vasodilating agent, was determined in whole blood or plasma by HPLC with papaverine as internal standard after absorption of the alkaline sample on an Extrelut column and elution with diethylether-methylene chloride (70:30, v/v). The eluate was evaporated and the residue was dissolved in 100 microL of the mobile phase; 20 microL of this solution were injected into a mu Bondapak C18 column (10 microns) using acetonitrile-0.125M potassium dihydrogen phosphate (40:60, v/v) as mobile phase and UV detection at 280 nm, followed by UV spectrum identification (between 200 and 350 nm) with a photodiode array detector. The method is rapid (giving response within 20 min), reproducible, selective, and sensitive. It can be applied for pharmacokinetic studies and for both clinical pharmacology and forensic toxicology. PMID- 2314058 TI - Drug use in patients admitted to a university trauma center: results of limited (rather than comprehensive) toxicology screening. AB - The results of rapid toxicology screening of paired blood and urine samples from 936 patients admitted to a university trauma center during the calendar year 1988 were reviewed in order to determine the drugs detected by use of a relatively limited (rather than comprehensive) screening procedure and to define the demographic characteristics of the positive population. Of the 936 cases, 65% (610) were positive for one or more drugs: ethanol (436), cocaine and/or benzoylecgonine (164), sympathomimetic amines (142), phencyclidine (40), narcotic analgesics (36), salicylates (17), and barbiturates (9). Of the positive screens, 70% (426) demonstrated only one drug or parent drug/metabolite combination. Positives were obtained from 69% of men, 50% of women, 80% of American Indians, 75% of Blacks, 66% of Latins, 65% of Caucasians, 60% of undetermined race, and 38% of Orientals screened. The age group 21-40 years accounted for 69% of positives. Rapid, limited admission toxicology screening of trauma patients can still provide useful information. PMID- 2314059 TI - Liquid chromatographic determination of reduced haloperidol and haloperidol concentrations in packed red blood cells from humans. AB - Haloperidol (H) is a neuroleptic drug that has one known biologically active metabolite, reduced haloperidol (RH). A liquid chromatographic method is described for the determination of both compounds in human red blood cell (RBC) samples. The drugs were extracted into hexane at high pH and back-extracted into 0.1M HCl. The acid solution was then analyzed by reversed-phase chromatography under the following conditions: column was ultrasphere ODS; eluant was acetonitrile:0.085M phosphate buffer (30:70), final pH was 3.5, flow rate was 2 mL/min; detection was by light absorption at 246 nm for H and 220 nm for RH. The minimum limits of quantitation for H and RH were 0.25 and 0.1 ng/mL of packed RBC respectively. For six selected patients on 10 or 20 mg per day of oral haloperidol the RBC to plasma concentration ratios for RH and H were 2.20 +/- 0.9 (SD) and 0.81 +/- 0.26, respectively. The data indicate that RH is more concentrated in RBC than in plasma. PMID- 2314060 TI - Electrothermal atomic absorption spectrometric determination of cadmium and nickel in urine. AB - This paper describes two relatively simple methods for the microdetermination of urinary cadmium (U-Cd) and urinary nickel (U-Ni) using electrothermal atomic absorption spectrometry. Reduction of nonspecific absorption interferences was achieved by temperature programming and background correction using a deuterium arc lamp. Within-run CVs were less than 5% for both U-Cd and U-Ni. Day-to-day variation was less than 8.1% for U-Cd and less than 8.0% for U-Ni. The typical limit for detection was 0.08 micrograms/L for U-Cd and 0.1 micrograms/L for U-Ni. The methods described are useful for mass screening of low level exposure to Cd or Ni. PMID- 2314061 TI - Limits of linearity and detection for some drugs of abuse. AB - The limits of linearity (LOL) and detection (LOD) are important factors in establishing the reliability of an analytical procedure for accurately assaying drug concentrations in urine specimens. Multiple analyses of analyte over an extended range of concentrations provide a measure of the ability of the analytical procedure to correctly identify known quantities of drug in a biofluid matrix. Each of the seven drugs of abuse gives linear analytical responses from concentrations at or near their LOD to concentrations several-fold higher than those generally encountered in the drug screening laboratory. The upper LOL exceeds the Department of Navy (DON) cutoff values by factors of approximately 2 to 160. The LOD varies from 0.4 to 5.0% of the DON cutoff value for each drug. The limit of quantitation (LOQ) is calculated as the LOD + 7 SD. The range for LOL is greater for drugs analyzed with deuterated internal standards compared with those using conventional internal standards. For THC acid, cocaine, PCP, and morphine, LOLs are 8 to 160-fold greater than the defined cutoff concentrations. For the other drugs, the LOL's are only 2 to 4-fold greater than the defined cutoff concentrations. PMID- 2314062 TI - Determination of sodium fluoroacetate (Compound 1080) in biological tissues. AB - A sensitive gas chromatographic method was developed for the determination of sodium fluoroacetate (Compound 1080 and 1080 poison) in baits and avian tissues. The procedure involves extraction of 1080 with acetone/water (8:1) followed by derivatization with pentafluorobenzyl bromide. Cleanup of the esterified extracts was carried out using minicolumns containing Florisil and the eluates were subsequently analyzed by electron capture gas chromatography. Bait samples were initially screened by thin-layer chromatography and identity of derivatized extracts was confirmed by gas chromatography/mass spectrometry. PMID- 2314063 TI - Cross-reactivity of amphetamine analogues with Roche Abuscreen radioimmunoassay reagents. AB - Cross-reactivity of amphetamine analogues with the Abuscreen amphetamine radioimmunoassay reagents was determined for both the standard and high specificity antibody systems. Compounds tested included 2-methoxyamphetamine, 4 hydroxymethamphetamine, 2,5-dimethoxyamphetamine (DMA), 4-bromo-2,5 dimethoxyamphetamine (DOB), 4-bromo-2,5-dimethoxy-beta-phenethylamine (BDMPEA), 3,4,5-trimethoxyamphetamine (TMA), 3,4-methylenedioxyamphetamine (MDA), N,N dimethyl-3,4-methylenedioxyamphetamine and N-hydroxy-3,4 methylenedioxyamphetamine (N-OH MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), 2,5-dimethoxy-4-ethylamphetamine, 2,5 dimethoxy-4-methylamphetamine (DOM), and 3,4,5-trimethoxyphenethylamine (mescaline). Blank negative reference material was spiked with 1,000 to 100,000 ng/mL of the amphetamine analogue and used as sample in the assays. MDA was the only analogue that showed cross reactivity equal to or greater than that of amphetamine. None of the other analogue compounds demonstrated a positive result at even the highest concentration; however several showed depressed counts at various concentration levels. PMID- 2314064 TI - A simple high-performance liquid chromatographic method for the measurement of 2 methylsulfonylpyridine in plasma. AB - A simple and sensitive high-performance liquid chromatographic (HPLC) method for the analysis of 2-methylsulfonylpyridine (2-MSP) in plasma has been developed. Up to 1 mL of plasma containing 2-MSP and an internal standard was extracted with 3 mL of methylene chloride, usually twice, evaporated to dryness, resuspended in mobile phase, and chromatographed on two 15-cm C8 reversed-phase LC columns in series. The mobile phase was 5% acetonitrile in water with a flow rate of 1 mL/min and ultraviolet detection was at 260 nm. Extraction of plasma produced no interfering endogenous components and the recovery of 2-MSP was 60-70%. The intraday and interday statistics of 2-MSP standard curves from 10 to 320 ng in plasma demonstrate that the assay is sensitive and precise using either human or monkey plasma and any plasma volume up to 1 mL. PMID- 2314065 TI - Extraction of 6-monoacetylmorphine from urine. AB - An efficient and improved procedure for the extraction of 6-monoacetylmorphine (6 MAM) from urine is described. The procedure uses a 10% isobutanol in methylene chloride solution for initial extraction of 6-MAM, back extraction with acidic sodium acetate, and then another alkaline extraction into 10% isobutanol in methylene chloride. Compared to solid-phase extraction, this method provided significant improvement in 6-MAM recovery, along with the elimination of extraneous peaks when analyzed by GC/MS. PMID- 2314066 TI - An example of cocaine tolerance in a gunshot wound fatality. AB - A 29-year-old male received a fatal gunshot wound to the head during an altercation. Routine toxicological followup on the victim revealed a concentration of 30 mg/L of cocaine in the blood. The case history presented suggests that the concentration achieved by this individual was the result of a physiological tolerance developed from years of consistent recreational use and not by an intentional or accidental overdose. PMID- 2314067 TI - Quality control data for low blood lead concentrations by three methods used in clinical studies. AB - During several clinical studies of blood lead (BPb) concentrations from environmental exposure, quality control data for three different methods of BPb analysis were compiled. Anodic stripping voltammetry by a commercial method (cASV), a modified method (mASV), and graphite furnace atomic absorption spectrophotometry (GFAA) were compared for precision at low BPb concentrations (less than 25 micrograms/dL) analyses. Both duplicate and interassay precision, as well as direct determinations of intraassay precision, were less for GFAA. The mASV incorporated calibration with lower BPb standards than used in the commercial protocol. This appeared to correct nonlinearity in response at lower BPb and reduced the bias between ASV and GFAA at BPb concentrations typical of environmental exposure levels. PMID- 2314069 TI - Predicting voice quality of deaf speakers on the basis of glottal characteristics. AB - Twenty profoundly deaf and 5 normal-hearing subjects produced 225 sustained vowels/a, i, u/at different pitch levels and 75 phonetically balanced sentences, while vocal fold vibration was recorded through an electrolaryngograph (ELG). The utterances recorded on audio tape were judged by 10 experienced listeners on general voice quality, breathiness, hoarseness, and laryngeal strain on a 5-point scale. Seven parameters describing time-domain characteristics of the ELG-signal were extracted online by a special purpose computer system. Measurements were made over 500 consecutive vibratory cycles (10-cycle window), yielding a mean and standard deviation for each parameter per utterance. All data were submitted to analysis of variance and multiple regression analyses. Multiple correlations between glottal parameters and judged voice deviations varied between .46 and .70 indicating that overall prediction cannot reliably be based on these parameters, although severe cases of deaf voice deviations may be detectable. PMID- 2314070 TI - Rapid manual abilities in spasmodic dysphonic and normal female subjects. AB - This study quantitatively examined upper extremity motor performance in 18 spasmodic dysphonic females, in comparison to matched normal controls, across variables of finger lift reaction time, index finger tapping speed, and peg placing (Purdue Pegboard) speed. Significant differences were noted for both upper extremities on the finger tapping and pegboard tasks, with better performance by the controls. A linear combination of these manual variables was able to discriminate the spasmodic dysphonic from matched normal subjects with 78% accuracy. Motor performance was uncorrelated with psychometric measures of anxiety and depression in both groups. The dysphonic subjects exhibited a significant correlation between nondominant finger tapping speed and severity ratings of motor speech impairment. Possible localizing significance of these findings is discussed. PMID- 2314068 TI - Listener experience and perception of voice quality. AB - Five speech-language clinicians and 5 naive listeners rated the similarity of pairs of normal and dysphonic voices. Multidimensional scaling was used to determine the voice characteristics that were perceptually important for each voice set and listener group. Solution spaces were compared to determine if clinical experience affects perceptual strategies. Naive and expert listeners attended to different aspects of voice quality when judging the similarity of voices, for both normal and pathological voices. All naive listeners used similar perceptual strategies; however, individual clinicians differed substantially in the parameters they considered important when judging similarity. These differences were large enough to suggest that care must be taken when using data averaged across clinicians, because averaging obscures important aspects of an individual's perceptual behavior. PMID- 2314071 TI - Some effects of advanced aging on the visual-language processing capacity of the left and right hemispheres: evidence from unilateral tachistoscopic viewing. AB - The present study investigated the effects of advanced aging on hemispheric organization for visual-linguistic processing. Lexical decision vocal-reaction times of geriatric subjects were measured for unilaterally presented concrete and abstract nouns in an attempt to obtain an index of differential left and right hemispheric processing ability. Results of an ANOVA procedure showed that reaction times were significantly faster when subjects were presented the stimulus items in their right visual fields, regardless of whether the item was a concrete or abstract word. An ANOVA procedure applied to the arcsine of the percentages of occurrence of false-positive and false-negative error types showed a significant interaction between the error type and visual field variables. Post hoc tests showed left visual field, false-positive errors occurred significantly more often than the remaining visual field, error type configurations. Finally, for the reaction time data, a significant correlation existed between the two visual fields for the concrete and abstract items. Collectively, such findings were consistent with a callosal relay model of neurolinguistic organization, suggesting that the right hemisphere's ability to perform lexical decisions was diminished in the present group of elderly subjects. PMID- 2314072 TI - Tracking of a "moving" fused auditory image under conditions that elicit the precedence effect. AB - Pursuit auditory tracking of a fused auditory image (FAI), based on stimulus conditions known to elicit the precedence effect phenomenon in sound localization, was investigated in 36 normal subjects and in a small group of subjects with known neuropathology. Movement of the FAI was simulated by incrementally varying the delay between two clicks presented, one each, from two loudspeakers placed on opposite sides of the listener. The group of normal listeners tracked the movement of the FAI without difficulty and with great accuracy; the perceived location of the FAI varied linearly with the interspeaker delay. The sensitivity of the task in detecting neural timing or integration deficits was investigated in 5 subjects with neuropathology, including subjects with unilateral temporal lobe lesions, multiple sclerosis, or dyslexia. These disorders, previously shown to disrupt neural timing, yielded characteristic patterns of tracking inaccuracy for this task. These subjects had no difficulty localizing either a moving unitary click source or sounds in daily life. These data support the suggestion that sound localization using stimulus conditions known to elicit the precedence effect places greater demands on neural timing and integration than conventional tests of localization, and may provide a more sensitive index of neural function. PMID- 2314073 TI - Hearing loss, aging, and speech perception in reverberation and noise. AB - The present investigation examined the effect of reverberation and noise on the perception of nonsense syllables by four groups of subjects: younger (less than or equal to 35 years of age) and older (greater than 60 years of age) listeners with mild-to-moderate sensorineural hearing loss; younger, normal-hearing individuals; and older adults with minimal peripheral hearing loss. Copies of the Nonsense Syllable Test (Resnick, Dubno, Huffnung, & Levitt, 1975) were re recorded under four levels of reverberation (0.0, 0.6, 0.9, 1.3 s) in quiet and in cafeteria noise at +10 dB S:N. Results suggest that both age and amount of pure-tone hearing loss contribute to senescent changes in the ability to understand noisy, reverberant speech: pure-tone threshold and age were correlated negatively with performance in reverberation plus noise, although age and pure tone hearing loss were not correlated with each other. Further, many older adults with minimal amounts of peripheral hearing loss demonstrated difficulty understanding distorted consonants. PMID- 2314074 TI - Relationships between selected auditory and phonatory latency measures in normal speakers. AB - Interaction between auditory and phonatory systems was explored in normal speakers by comparing laryngeal reaction time (LRT) with interpeak intervals from the auditory brainstem response (ABR) obtained using high and low stimulus presentation rates. Thirty-four subjects with no history of neurological or speech-language disorders and normal hearing sensitivity participated. Interpeak intervals were derived from ABR's recorded for each ear at rates of 21.1 and 91.1 clicks/s. LRT responses were obtained by instructing subjects to sustain an /s/ and then phonate an /a/ as fast as possible following visual cues. Two measures of reaction time performance were derived, Mean Laryngeal Reaction Time (MLRT) and Best Laryngeal Reaction Time (BLRT). Linear regression analyses were completed between each measure of reaction time performance and each ABR interpeak interval. Using either LRT measure, two significant (p less than .05) positive linear relationships were found. One involved the interpeak interval between Waves III and V and the other involved the interpeak interval between Waves I and V. Both were recorded at high stimulus presentation rates. These results support the small body of literature from normal speakers, stutterers, and spasmodic dysphonics suggesting interaction between the auditory and phonatory systems at the brainstem level. PMID- 2314075 TI - Acquisition of correct vowel production: a quantitative case study. AB - There have been relatively few studies of the course of acquisition of correct vowel production. The present study suggests this gives an illusory impression that vowels are acquired easily and are of little theoretical interest. Despite a relatively precocious rate of vocabulary acquisition over the period from 14 to 20 months, the subject studied produced less than 60% of her vowels correctly according to evidence from phonetic transcriptions. A complex pattern of vowel preferences and errors was only partially related to typical prespeech babbling preferences, but was strongly related to word structure variables (monosyllabic vs. disyllabic) including stress patterns of disyllabic words, as reflected in patterns of relative frequencies of vowels in stressed and unstressed syllables. Consonant-vowel interdependence was observed, in both the favoring of high front vowels in the environment of alveolar consonants, and a reciprocal relation between vowel reduplication and consonant reduplication in disyllabic words. PMID- 2314076 TI - Visual biasing of normal and impaired auditory speech perception. AB - Intersensory biasing occurs when cues in one sensory modality influence the perception of discrepant cues in another modality. Visual biasing of auditory stop consonant perception was examined in two related experiments in an attempt to clarify the role of hearing impairment on susceptibility to visual biasing of auditory speech perception. Fourteen computer-generated acoustic approximations of consonant-vowel syllables forming a /ba-da-ga/ continuum were presented for labeling as one of the three exemplars, via audition alone and in synchrony with natural visual articulations of /ba/ and of /ga/. Labeling functions were generated for each test condition showing the percentage of /ba/, /da/, and /ga/ responses to each of the 14 synthetic syllables. The subjects of the first experiment were 15 normal-hearing and 15 hearing-impaired observers. The hearing impaired subjects demonstrated a greater susceptibility to biasing from visual cues than did the normal-hearing subjects. In the second experiment, the auditory stimuli were presented in a low-level background noise to 15 normal-hearing observers. A comparison of their labeling responses with those from the first experiment suggested that hearing-impaired persons may develop a propensity to rely on visual cues as a result of long-term hearing impairment. The results are discussed in terms of theories of intersensory bias. PMID- 2314077 TI - Perception of terminal fall contours in speech produced by deaf persons. AB - Eight deaf children produced each of nine sentences. F0 measures were obtained at several locations within each utterance (starting F0, peak F0, peak F0 in the final syllable, and final F0). The relative timing of each F0 measure (ms from onset of the utterance) was also determined. In addition, several difference measures were derived. Listeners experienced with the speech of the deaf were asked to judge whether they heard a terminal fall, rise, or a flat final intonation contour in each utterance. A multiple linear regression analysis was used to determine if any combination of the acoustic measures could predict listeners' responses. The only variable that made a significant contribution to the regression function was the temporal interval between the terminal peak F0 and the final F0. That is, the more slowly the contour fell the more likely listeners were to perceive the contour as flat, regardless of the amount (in Hz or percentage F0) by which it fell. The regression equation accounted for a statistically significant but not large proportion of the total variance. This suggests that other variables, not measured in this study, play an important role in the perception of utterance final intonation contours in the speech of the deaf. PMID- 2314078 TI - Speech reception in reverberation related to temporal resolution. AB - In this study, the influence of temporal properties of the auditory system on speech recognition, either in noise or in both noise and reverberation, has been investigated. Temporal resolution parameters consisted of both the temporal resolution factor (TRF) and the minimum detectable gap (MDG). TRFs were measured for probe-tone frequencies of 500, 1000, and 3000 Hz; MDGs were measured for octave-band noises centered at 500, 1000, and 3000 Hz and for a wideband noise. TRF and MDG proved to be rather independent parameters of temporal resolution. For both temporal-resolution parameters, there was considerable overlap between the performance of the normal-hearing and hearing-impaired listeners. A correlation analysis shows that MDG for wideband noise is related to speech recognition in reverberation. However, there is a mutual dependence of speech recognition and MDG on the pure-tone audiogram. PMID- 2314079 TI - Language learning in a prospective study of otitis media with effusion in the first two years of life. AB - We report cross-sectional findings on children's early experience with otitis media with effusion (OME) related to hearing over time and emerging receptive and expressive language skills on the Sequenced Inventory of Communication Development Scale (SICD). Tympanometry and otoscopy on the same day are combined to diagnose OME. Hearing from 6 to 12 months is significantly related to scores on the SICD beginning with receptive language at 12 months. At 18 and 24 months, both receptive and expressive language are significantly related to average hearing from 6 to 18 months. Better language is associated with better average hearing levels. These findings suggest that the relationship between OME and language is mediated by hearing. It remains to be seen whether these relationships persist as the children continue to develop language. PMID- 2314080 TI - A note on intelligence assessment within studies of specific language impairment. AB - The purpose of this paper is to review the procedures, reported in three journals, that researchers have adopted to evaluate the intelligence of children with specific language impairment. The results indicated that researchers used one of the following procedures: no mention of intelligence, statements of negative history for mental retardation (without further documentation), reporting cut-off scores on one or more standardized assessment instruments, reporting means on one or more standardized assessment instruments, or reporting individual test scores from such instruments. A majority of researchers adopted the procedures in the first three categories. Implications of such reporting procedures are discussed. PMID- 2314081 TI - Some constraints on functionally disordered phonologies: phonetic inventories and phonotactics. AB - The phonological systems of 40 functional misarticulators, ages 40 to 80 months were examined in terms of the nature and variation of phonetic inventories and phonotactic constraints. It was found that these properties of disordered systems were governed by severe constraints that yielded a typological characterization of such systems along with associated implicational laws. The principles governing disordered systems were also found to parallel closely the principles governing normal first language acquisition. The evidence suggests that at least these properties of disordered systems represent delays in the normal acquisition process and are not otherwise deviant. The assessment and treatment of functional disorders along with the projection of learning patterns can thus appeal to principles governing such phonological systems. PMID- 2314082 TI - Masking of tone bursts by modulated noise in normal, noise-masked normal, and hearing-impaired listeners. AB - Threshold of 4.6-ms tone bursts was measured in quiet and in the presence of a 100% sinusoidally amplitude-modulated speech-shaped noise. For the modulated noise conditions, the onset of the tone burst coincided either with the maximum or the minimum modulator amplitude. The difference in these two masked thresholds provided an indication of the psychoacoustic modulation depth, or the modulation depth preserved within the auditory system. Modulation frequencies spanning the modulation spectrum of speech (2.5 to 20 Hz) were examined. Tone bursts were 500, 1400, and 4000 Hz. Subjects included normal listeners, normal listeners with a hearing loss simulated by high-pass noise, and hearing-impaired listeners having high-frequency sensorineural hearing loss. Normal listeners revealed a psychoacoustic modulation depth of 30-40 dB for the lowest modulation frequencies which decreased to about 15 dB at 20 Hz. The psychoacoustic modulation depth was decreased in the normal listeners with simulated hearing loss and in the hearing impaired listeners. There was general agreement in the data, however, for the latter two groups of listeners suggesting that the normal listeners with hearing loss simulated by an additional masking noise provided a good representation of the performance of hearing-impaired listeners on this task. PMID- 2314083 TI - Temporal effects in simultaneous masking by vowel and consonant-vowel maskers. AB - Temporal effects in simultaneous masking were studied using synthetic vowel (V) and consonant-vowel (CV) maskers. For the steady-state V maskers (/i,a,u/), signals were presented at the beginning or in the temporal center of the masker. The masking patterns generally reflected the formant differences among the vowels, and the formant structure of each V masker was more clearly revealed when the signal was presented in the temporal center of the masker. For the CV maskers (/bi,gi/), signals were presented at the beginning of the (consonant portion of the) masker, at the beginning of the vowel portion of the masker, or in the temporal center of the masker. The second-formant difference between the maskers (observed acoustically at their onset) was generally revealed in the masking patterns when the signal was presented at the beginning of the consonant; this difference in the masking patterns was also present, to a lesser extent, when the signal was presented at the beginning of the vowel, where the two maskers were identical acoustically. The masking patterns for the two CV maskers were virtually identical when the signal was presented in the temporal center of the masker. These data extend previous tone-on-tone masking data and suggest that the auditory system requires a certain amount of time to represent most accurately the acoustic spectrum of both steady-state and dynamic complex maskers. PMID- 2314084 TI - Frequency, intensity, and target matching effects on photoglottographic measures of open quotient and speed quotient. AB - Measurements of Open Quotient (OQ) and Speed Quotient (SQ) were made from photoglottographic signals of normal male subjects during phonation. Samples were obtained at spontaneous levels of fundamental frequency and intensity, and at nine specified frequency/intensity combinations. OQ increased with fundamental frequency. OQ change was not significant for change in intensity and there was no significant interaction between frequency and intensity. Changes in SQ with variations of frequency and intensity were not significant. However, SQ did increase significantly when spontaneous phonation was compared to target matching phonation at similar frequency/intensity. Changes in both OQ and SQ across comfortable frequency and intensity ranges were relatively small in comparison to changes in OQ and SQ reported for pathological phonation. PMID- 2314085 TI - Speech breathing in children and adolescents. AB - An investigation was conducted to elucidate the nature of speech breathing in children and adolescents and to determine if sex and age influence performance. Eighty healthy boys and girls representing four age groups (7, 10, 13, and 16 years) were studied using helium dilution to obtain measures of subdivisions of the lung volume and using magnetometers to obtain measures of resting tidal breathing and speech breathing. Results for subdivisions of the lung volume and resting tidal breathing revealed sex- and age-related differences, most of which were attributable to differences in breathing apparatus size. Results for speech breathing indicated that sex was not an important variable, but that age was critical in determining speech breathing performance. The most substantial differences were between the 7-year-old group and older groups. These differences were characterized by larger lung volume, rib cage volume, and abdominal volume initiations and terminations for breath groups, larger lung volume excursions per breath group, fewer numbers of syllables per breath group, and larger lung volume expenditures per syllable for the 7-year-old group compared to older groups. In most respects, speech breathing appeared adultlike by the end of the first decade of life. Clinical implications regarding these findings are offered. PMID- 2314087 TI - School-age children's metalinguistic awareness of grammaticality in verb form. AB - This study investigated 6-, 7-, and 8-year-old children's ability to monitor grammaticality in the past progressive, perfect progressive, and perfect verb forms. The children achieved a significantly higher rate of accurate judgments monitoring grammatical forms that ungrammatical forms. Age was a significant factor in error identification. Eight-year-olds were substantially better at identifying ungrammatical forms than were their younger schoolmates. Verb form, in conjunction with type of anomaly, significantly varied with respect to ease of identification. Errors of the auxiliary and suffix were easier for children to identify than an adverbial error which required a sentence analysis to determine the incompatibility. The context surrounding ungrammatical verb forms significantly affected monitoring ability. Anomalous forms in unrelated sentences were easier to identify as ungrammatical than anomalous forms in sentences taken from a story the children had just heard. It appears that school-age children prefer to maintain the semantic intent of the message rather than critically search for grammatical errors. PMID- 2314086 TI - Development of children with early language delay. AB - Four children with early language delays (ELD) were compared to a control group of 12 children with respect to their preschool language abilities from age 2 1/2 to 5 years and their verbal skills at the end of Grade 2. The language-delayed children each initially showed severe and broad impairments in syntactic, phonological, and lexical production. Over time, their deficits became milder and more selective, such that normal or nearly normal speech and language proficiency was exhibited by age 60 months. Nevertheless, when followed up 3 years later, three of the four cases were severely reading disabled. These findings are discussed with respect to prior findings and hypotheses about the sequelae of early language delay and the relationship of language development to reading achievement. PMID- 2314088 TI - Imitation of intonation by infants. AB - Children between 9 and 12 months of age were studied to determine if they would spontaneously imitate either the average fundamental frequency or the fundamental frequency contour of their speaking partners. In the first experiment, children were recorded at home as they interacted with their fathers and mothers. Acoustic analyses failed to reveal any tendency on the part of the infants to adjust vocal pitch, amplitude, or duration to those of their speaking partners. In a second experiment, children were recorded while interacting with their parents in a laboratory setting. Again, there were no indications that the children imitated the vocal patterns of their speaking partners. PMID- 2314089 TI - Frequency selectivity and comodulation masking release in adults and in 6-year old children. AB - Frequency selectivity and comodulation masking release (CMR) for a 1000-Hz signal frequency were examined in 6-year-old children and adults. An abbreviated measure of frequency selectivity was also conducted for a 500-Hz signal. Frequency selectivity was measured using a notched-noise masking method, and CMR was measured using narrow bands of noise whose amplitude envelopes were either uncorrelated or correlated. There were 6 listeners in each age group. No differences were observed between the adults and children for either auditory measure. Similarly, no differences were observed in the ability to detect a pure tone signal in a relatively wideband noise masker. When the masking noise was narrowband, however, the masked thresholds of the children were higher than those of the adults. Two characteristics that distinguish narrowband noise from wideband noise are: (1) narrowband noise has a pitch quality corresponding to its center frequency, whereas wideband noise does not have definite pitch; (2) the intensity fluctuations are relatively greater in narrowband noise than in wideband noise. This may suggest that 6-year-old children have a reduced ability to detect signals in noise backgrounds where the signal has perceptual qualities similar to the noise, or in noise backgrounds having a high degree of fluctuation. PMID- 2314090 TI - The effect of hemodilution on blood flow regulation in normal and postischemic intestine. AB - We investigated the effect of hemodilution on intestinal blood flow and oxygen consumption (VO2) in denervated rat small intestinal preparations. In one series of experiments, intestinal blood flow (IBF) and intestinal oxygen extraction (A VO2) were measured during graded decreases in perfusion pressure. Control animals underwent consecutive studies without hemodilution; experimental animals were studied before and after isovolemic hemodilution. In a second series of experiments, normovolemic hemodilution was performed in experimental animals NH while hematocrit was maintained in controls, C. Preparations were then subjected to 30 min of complete ischemia followed by 30 min of reperfusion. Hemodilution (40.5 +/- 0.8% to 17.2 +/- 2.5%) decreased A-VO2 (3.9 +/- 0.5 to 2.1 +/- 0.4 ml/dl; P less than 0.05) but increased IBF (77.5 +/- 9.8 to 132.1 +/- 15.0 ml/min/100 gm; P less than 0.01). IBF was maintained to the limit of pressure:flow autoregulation (69 mmHg). Below this point, decreases in IBF were accompanied by increases in A-VO2 thus maintaining VO2. At a much lower "critical pressure" (42 mmHg) maximal oxygen extraction was reached and VO2 decreased with IBF. In the second series of experiments, hemodiluted animals (hematocrit 25 +/- 1%) studied during the reperfusion period maintained higher O2 consumption [30 min values (ml/min/100 gm): 4.8 +/- 0.9 NH vs 1.6 +/- 0.2 C, P less than 0.01] and A-VO2 difference [30 min values (vol%): 3.9 +/- 0.4 NH vs 2.1 +/- 0.4 C, P less than 0.005] than control animals (hct 33 +/- 2%). Hemodilution does not impair the intestine's ability to maintain O2 consumption during hypotension and hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314092 TI - Kinetics of leukocyte sequestration in the lungs of acutely septic primates: a study using 111In-labeled autologous leukocytes. AB - To further clarify the role of leukocytes in the pathogenesis of ARDS, we studied the localization and kinetics of leukocyte migration using 111In-labeled autologous white cell scans (111In wbc scans) in four primates made acutely septic with infusions of Escherichia coli. Whole body images were obtained with a gamma camera and were acquired on computer every 15 min beginning immediately after the E. coli infusion. Simultaneous measurements of C5a and peripheral blood leukocyte count were also obtained. Within 5 min of initiating sepsis, three major events occurred: complement activation as measured by the production of C5a, a profound fall in peripheral leukocyte count, and a significant increase in the sequestration of leukocytes in the lungs. The pulmonary sequestration reached a peak at 15 min with a mean of 152% of baseline activity. This sequestration consisted of a population that was predominantly neutrophils. Damage to the pulmonary capillary endothelium was demonstrated by an increase in extravascular lung water. The results support a role for neutrophils and complement as mediators in the pathogenesis of ARDS. PMID- 2314091 TI - Cytotoxicity to cultured human keratinocytes of topical antimicrobial agents. AB - Cultured skin grafts administered clinically for closure of burn wounds may be contacted by topically applied antimicrobial agents. A study was performed to assess whether commonly used topical antimicrobial agents are toxic to cultured human keratinocytes (HK) in vitro. Serum-free MCDB 153 culture medium containing Neosporin G.U. irrigant (Neomycin, 40 micrograms/ml-polymyxin B sulfate, 200 units/ml) and a standard tissue culture antimicrobial agent of penicillin (10,000 units/ml)-streptomycin (10,000 micrograms/ml)-amphotericin B (25 micrograms/ml) had no effect on the keratinocyte growth rates when compared to standard MCDB 153 medium without antibiotics. Medium containing Sulfamylon (mafenide acetate, 0.85%), Polysporin (polymyxin B sulfate, 1 x 10(4) units/ml-bacitracin, 500 units/ml), gentamicin sulfate (0.1%), modified Dakins solution (25%), and acetic acid (0.25%) all showed statistically significant (P less than 0.01) decreases in keratinocyte growth rates. This data suggests that commonly applied antimicrobials may not be appropriate for cultured grafts in the concentrations that are used clinically. PMID- 2314094 TI - Some determinants of papaverine-induced femoral artery pressure gradients. AB - The accuracy and reliability of papaverine-induced central arterial to common femoral artery pressure gradients, frequently used to estimate the hemodynamic significance of aortoiliac stenosis, depend on a reproducible, between patient increase in resting common femoral artery blood flow because of the linear relationship between pressure gradient and flow. Blood flow variability and the effect of proximal and distal occlusive disease on femoral artery pressure gradient and flow were determined by three methods: intraoperative electromagnetic blood flow measurements, hemodynamic model analysis, and flow calculations using intraoperative segmental resistance measurements. The ratios of papaverine-induced hyperemic to resting common femoral artery blood flow were 2.80 +/- 0.781 (mean +/- 1 SD, n = 19) for occluded and 3.07 +/- 0.819 (n = 13, P greater than 0.5) for open superficial femoral arteries, respectively, when the papaverine-induced central arterial to common femoral artery mean pressure gradient was less than 10 mm Hg. The flow ratios were 2.70 +/- 1.093 (n = 16) and 2.93 +/- 1.027 (n = 10, P greater than 0.5) for superficial femoral occlusion and patency, respectively, when the central to femoral mean pressure gradient was greater than or equal to 10 mm Hg. Hemodynamic model analysis predicts that superficial femoral artery occlusion reduces the hyperemic to resting common femoral artery flow ratio from 2 to 1.8 and from 3 to 2.5. The mean values of segmental resistance measured intraoperatively in 17 additional limbs with and in 17 without superficial femoral occlusion predict a reduction in flow ratios from 2 to 1.75 and from 3 to 2.44 when the superficial femoral is occluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314093 TI - A model of reversible obstructive jaundice in the rat. AB - A model of reversible, extrahepatic biliary obstruction is described. Vessel loop blockade of the biliary tree results in obstructive jaundice while removal of the exteriorized vessel loop provides internal biliary drainage without subsequent laparotomy. This technique combined with a system for chronic venous infusion and arterial blood sampling in the unrestrained rat is ideal for long-term metabolic studies of obstructive jaundice. Male Fisher 344 rats (275-350 g) underwent either the combined procedure of total biliary tract blockade and vascular access or sham operation. Mean serum bilirubin was significantly elevated (12.7 +/- 8.9 mg/dl) in the experimental group and following relief of biliary obstruction significantly dropped below 1 mg/dl in all animals except one. Concomitant changes in alkaline phosphatase, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase were seen. Experimental and control rats initially lost weight following laparotomy; however, mean body weight stabilized by the 5th postoperative day and was similar in both groups on the 10th postoperative day. This combined procedure is a simple, effective and reproducible method of obstructive jaundice. PMID- 2314095 TI - Hemodynamics and metabolism during surface-induced hypothermia in the dog: a comparison of pH management strategies. AB - The management of blood pH during hypothermia remains controversial. The present study was designed to determine whether hemodynamics and oxygen consumption during hypothermia are different between the alpha-stat and pH-stat strategies. Theoretical considerations of enzyme kinetics suggest that the alpha-stat strategy would result in a higher oxygen consumption during hypothermia. Because hypothermia is used to decrease oxygen consumption for protection during ischemia, a pH scheme that results in a greater oxygen demand for any level of ischemia would be detrimental. The core temperature of 22 dogs was lowered to 26 degrees C by combined surface cooling and gastric irrigation. Either the alpha stat (N = 9) or the pH-stat (N = 13) pH strategy was used. The arterial pressure was different between the two groups at 26 degrees C (65 +/- 6 vs 85 +/- 6 mm Hg, alpha-stat vs pH-stat, respectively, P less than 0.05). Neither systemic oxygen consumption nor the Q10 was different between groups. There were no differences in any other hemodynamic parameters. In summary, during moderate hypothermia alpha-stat pH management results in an arterial pressure lower than that of pH stat management, possibly resulting in improved peripheral perfusion. Despite theoretical predictions, the alpha-stat pH scheme does not result in an oxygen consumption higher than that of the pH-stat scheme. PMID- 2314096 TI - Experimental model of acute appendicitis in the rabbit with determination of leucine amino peptidase (LAP) and acid phosphatase (acid-P) activities in portal blood samples. AB - The activities of leucine amino peptidase (LAP) and acid phosphatase (Acid-P), conceivable markers of acute appendicitis, were determined in the portal blood of rabbits with acute appendicitis. An experimental model of acute appendicitis was established using No.-O silk ties to block the base of the appendix. The clinical and histopathological picture of acute appendicitis was seen after 12 hr in all the rabbits in the model group (9/9) and in none of the control group. Catheterization of the superior mesenteric vein was performed in rabbits with acute appendicitis, and portal blood samples were taken at 0, 6, and 12 hr for assay of LAP and Acid-P activities. No statistically significant difference between the experimental group and the control group, in the activities of LAP and Acid-P, was found at any time interval. The experimental model of acute appendicitis in the rabbit which is described here is simple and carries a high rate of success. This is probably the first report of using continuous catheterization and repeated sampling of portal blood, for the measurement of enzyme activities, in an experimental model of acute appendicitis. It was concluded that serum LAP and Acid-P activities cannot be used as markers for acute appendicitis. PMID- 2314097 TI - Role of noradrenaline in the pathogenesis of skin flap ischemic necrosis in the pig. AB - Clinically, ischemic necrosis is one of the most common complications in skin flap surgery, but the etiology is still unclear. The objective of the present experiments was to study the important role of the locally released noradrenaline in the pathogenesis of ischemic necrosis in acute and delayed random pattern skin flaps (4 x 10 cm) raised on both flanks of the pig. In Experiment 1, it was observed that 93, 96, and 94% of the skin contents of noradrenaline were depleted in skin flaps delayed for 2, 4, and 14 days, respectively, compared to the acute skin flaps (n = 8) raised in the same pig. Although the maximum depletion of noradrenaline in the delayed flaps occurred within 2 days of delay, significant (P less than 0.001) increase in the length of dye penetration in the delayed skin flaps was seen after 2 days of delay, compared to the acute skin flaps (n = 12). In Experiments 2 and 3, 5 days of intravenous phenoxybenzamine treatment, starting 2 days preoperatively and at the doses of 0.25, 0.5, 1.0, or 1.5 mg/kg/day, did not have any significant effect on the skin blood flow (n = 24) or viability (1 mg/kg/day; n = 32) in the acute skin flaps compared with the saline treated control. Similarly, 5 days of intravenous phentolamine treatment (5 mg/kg/day) also did not have any significant effect on the skin blood flow (n = 24) or viability (n = 32) of acute skin flaps compared with the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314098 TI - Second-degree burn healing: the effect of occlusive dressings and a cream. AB - Because occlusive dressings and some creams have been found to speed epithelialization of blade-induced wounds, we studied the effect of two occlusive dressings and a polyglycerylmethacrylate cream containing low concentration of fibronectin on epithelialization in second-degree burn wounds. Cylindrical brass rods were heated in a boiling water bath, removed, wiped dry, and placed (6 sec) on the skin of domestic pigs. The burned epidermis was removed and each burn wound was assigned to one of the following treatment groups: (1) air-exposed, (2) DuoDERM (hydrocolloid dressing; Squibb Co., New Jersey), (3) Opsite (polyurethane dressing; Smith & Nephew, New Jersey), or (4) experimental cream. Several burn wounds were excised from each treatment group on Days 6 to 14 after wounding. The excised burn wounds were incubated in 0.5 M NaBr for 24 hr which allowed separation of the epidermis from the dermis. The epidermis was examined macroscopically for defects in the area of the burn. Specimens were considered healed when a defect was not present. Neither of the occlusive dressings changed the rate of epithelialization as compared to air exposure. Wounds which were treated with the experimental cream epithelialized faster than the air-exposed wounds (P less than 0.025). PMID- 2314099 TI - Muramyl dipeptide improves mononuclear phagocyte system function in obstructive jaundice. AB - Previous studies have demonstrated depression of the mononuclear phagocyte system (MPS) of which the liver comprises 80-85% in animals subjected to 21 days of obstructive jaundice. This study examined the ability of a macrophage stimulant, muramyl dipeptide (MDP), to reverse MPS dysfunction in an obstructive jaundice rat model. Sixty-two male Sprague-Dawley rats underwent sham (n = 29) laparotomy or common duct ligation (CDL) (n = 33) and were studied after 21 days. Animals were injected with 1-3.5 X 10(6) Escherichia coli via a lateral tail vein, and colony-forming units (CFU) of the liver, lung, and spleen were determined at two time intervals: 30 min postinjection to determine the phagocytic activity of MPS (sham, n = 16; CDL, n = 20) and 24 hr postinjection to determine cytotoxic activity of MPS (sham, n = 13; CDL, n = 13). MDP (3 micrograms/g) was administered subcutaneously 24 hr prior to E. coli injection in 6 sham and 10 CDL rats studied at the 30-min time interval and 7 sham and 7 CDL rats studied at the 24-hr time interval. Pretreatment with MDP appeared to reverse the impairment of phagocytic activity in the liver of CDL rats returning it to the level of sham animals (P less than 0.05). However, pretreatment with MDP did not enhance the cytotoxic activity of the MPS as evidenced by higher CFU of E. coli in the liver, lung, and spleen of CDL animals pretreated with MDP as compared to CDL animals that did not receive MDP pretreatment. This increase was only significant in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314100 TI - Improved survival after pulmonary resection of metastatic colorectal carcinoma. AB - While hepatic resection of metastatic colorectal carcinoma is accepted as effective in selected patients, resection of metastases to other solid organs has not gained wide acceptance. We retrospectively reviewed the records of 49 patients who had resection of isolated pulmonary (18 patients) and hepatic (31 patients) metastases from the large bowel, comparing disease-free survival and overall survival. Tumor parameters analyzed included Dukes' stage, deoxyribonucleic acid (DNA) flow cytometry, and number of metastases. Dukes' B and diploid tumors had longer disease-free survival and overall survival than did Dukes' C and aneuploid tumors, though the difference was not significant. Patients with a single lung metastasis had a significantly longer disease-free survival (P = .02) than did patients with multiple metastases. Mean and median survival were longer in patients with lung metastases. Five-year actuarial survival was 19% for patients with liver metastases and 47% for patients with lung metastases. Resection of isolated pulmonary metastases from the large intestine results in survival comparable to or better than resection of hepatic metastases. An aggressive surgical approach is warranted in patients with isolated resectable pulmonary metastases of colorectal carcinoma. PMID- 2314101 TI - Spouse adjustment to cancer surgery: distress and coping responses. AB - Although often acknowledged, the impact of the surgical treatment of cancer on the spouse of the adult cancer patient is a largely unexplored area. The present study examined distress, coping, and appraisal among spouses (N = 36) and patients (N = 43) assessed prior to and following surgery. The results indicated that at both the presurgical and postsurgical period, spouses were exhibiting significantly greater distress than patients. Surprisingly, spouses' levels of distress remained fairly constant across the presurgery to postsurgery period, while the patients' distress decreased. Escape and avoidance behaviors were found to be maladaptive for spouses coping with their partners' surgical treatment. Appraisal was also found to be a critical factor in understanding individual reactions to the stress of cancer surgery. Spouses of cancer patients undergoing surgical treatment appear to be an underacknowledged population at risk. PMID- 2314102 TI - Do adrenal metastases from lung cancer develop by lymphogenous or hematogenous route? AB - In order to analyse the possible mode and pathways of adrenal metastases from lung cancer, the frequency of adrenal metastases ipsilateral and contralateral to the site of the primary cancer was investigated based on autopsied lung cancer cases. In 405 of 1,607 such cases, adrenal metastases could be found: on both sides, 234; ipsilateral only, 105; contralateral only, 66 cases. In the early stages of tumor progression, a striking difference can be seen between the two sides. Ipsilateral metastases were of significantly higher incidence in early metastatic tumor stages, but later, in cases having six or more involved organs, the ipsilateral/contralateral quotient reaches 1. It is postulated that in the early stages adrenal metastases from lung cancer probably develop mainly by lymphogenous, but later mainly by hematogenous routes. PMID- 2314104 TI - A study of cell membrane structure. AB - Neoplastic transformation has been associated with a variety of structural changes, among which are changes in membrane carbohydrates. Not much is known, though, e.g., how early in the tumourogenic event these changes take place and what effect these changes have on cell growth, invasion, and ability to metastasize. We were able to identify the B-D-Gal(1-3)DGal-NAc as a membrane carbohydrate component present in malignant laryngeal tissue, but not on adjacent normal mucous membrane. This carbohydrate structure was found to be present in metastatic as well as in nonmetastatic tumours. It was also found in well differentiated as well as poorly differentiated carcinomas. We suggest that changes in carbohydrate components on the cell membrane of the laryngeal cancer cell are an early event in tumour progression and probably are not related to the degree of invasion or the ability to metastasize. PMID- 2314103 TI - Is long-term follow-up justified after excision of a thin melanoma (less than or equal to 1.5 mm)? A retrospective analysis of 206 patients. AB - From 1964 to 1988, 231 patients underwent local excision as the single treatment of melanoma with a thickness of less than or equal to 1.5 mm. We investigated the prognostic value of several factors on cancer-specific survival and cancer specific disease-free survival, from time of excision on, by performing life table analysis on 206 evaluable patients. Recurrence developed in 11 patients; local recurrence occurred in four patients, hematogenic spread in three patients and lymph node metastases in another four patients. Six patients died as a result of the disease. Tumors with a thickness of less than or equal to 1.5 mm have an excellent prognosis regardless of the localization of the melanoma. At 15 years cancer-specific survival was 92.3% and cancer-specific disease-free survival was 86.9%. Recurrence was successfully treated with hope for cure in 4 patients. This figures does not justify aggressive follow-up for all patients. PMID- 2314105 TI - Long-term survival in patients treated for testicular seminoma. AB - Forty-eight patients with newly-diagnosed testicular seminomas were followed for a mean of 7 years after treatment. At the time of diagnosis, seminoma was confined to testis in 74% (36) and was metastatic to retroperitoneal lymph nodes in 15% (7) and to distant nodal sites or parenchymal organs in 10% (5). Ninety six percent remained free of disease, 94% in first complete remission (CR) and 2% after treatment of first recurrence. Long-term disease-free survival in CR per stage was 97% (35/36) for Stage I, 100% for Stage II, and 80% (4/5) for Stage III. However, three patients, who received prior chest radiation therapy (RT), died from acute myocardial infarction 2, 9, and 10 years after treatment and while free of disease. PMID- 2314106 TI - Separate annular strictures of the rectosigmoid colon secondary to unsuspected prostate cancer. AB - Rectal involvement from prostate cancer occurs in 1.5-11% of cases. A rarer presentation is that of a separate metastasis to the high rectosigmoid colon causing an annular stricture. We present our experience with six such cases who presented with gastrointestinal symptoms. Two of the cases had undergone intestinal resections. All 6 patients had radiographic evidence of an annular stricture in the rectosigmoid area. Retrospective review revealed evidence of metastatic disease in all cases in the form of abnormalities in one or more of the following: intravenous urography, radionuclide bone scan, liver spleen scan, acid phosphatase, or alkaline phosphatase. The mean survival was 9.3 months. This rare presentation of prostate cancer may be difficult to distinguish from primary colorectal cancer and therefore needs to be ruled out to avoid intestinal resections. PMID- 2314107 TI - Malignant melanoma metastatic to the thyroid as initial evidence of disseminated disease. AB - A 48-year-old Caucasian male with a 3 mm sub-ungual right middle finger melanoma underwent cisplatin forequarter perfusion, ray amputation, and ipsilateral axillary node dissection. Two months post-operatively he presented with a thyroid mass as initial evidence of disseminated disease. Subsequent workup also demonstrated pulmonary metastases. A total thyroidectomy radical neck dissection and multi-agent chemotherapy has controlled the disease in his neck. As far as we are aware, this is the first case report of malignant melanoma metastatic to the thyroid. The potentially beneficial role of surgery in the management of metastatic melanoma and the relation of melanoma to the hormonal axis is discussed. PMID- 2314108 TI - Plant-derived sweetening agents: saccharide and polyol constituents of some sweet tasting plants. AB - Samples of the sweet-tasting species Acanthospermum hispidum DC. (Compositae) (aerial parts), Boscia salicifolia Oliv. (Capparidaceae) (stem bark), Hovenia dulcis Thunb. (Rhamnaceae) (peduncles) and Inga spectabilis Willd. (Leguminosae) (arils) were acquired as part of a continuing search for high-intensity natural sweeteners of plant origin. Following their preliminary safety evaluation, the sweetness of these plants was traced to large amounts of sugars and polyols by taste-guided fractionation, which were identified and quantified using gas chromatography/mass spectrometry. The combined yields of sugars and polyols in the A. hispidum, B. salicifolia, H. dulcis, and I. spectabilis samples investigated were 6.9, 10.1, 18.4 and 12.1% w/w, respectively. These yields are much higher than the total saccharide and polyol content (2.4% w/w) of the sweet dried fruits of Thladiantha grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae), a species which has previously been reported to contain more than 1% w/w of the intensely sweet triterpene, mogroside V. The dried leaves of Symplocos tinctoria (L.) L'Herit. (Symplocaceae), which were not appreciably sweet, were found to contain only 2.0% w/w of sugars. The results of this investigation, therefore, suggest that unless the saccharide and/or polyol content of a plant part is well over 5% w/w, then it is unlikely to exhibit an overtly sweet taste, unless an intense sweetener is present. PMID- 2314109 TI - Stability of cannabinoids in dried samples of cannabis dating from around 1896 1905. AB - Cannabinoids from three samples of cannabis obtained from the Pitt-Rivers Museum, Oxford, and dating from the turn of the century were examined by gas chromatography and mass spectometry for the presence of cannabinoids. Although the samples were from different geographical locations, the profiles of constituent cannabinoids were similar. In common with other aged material, most of the cannabinoid content was present as cannabinol (CBN), the main chemical degradation product of the major psychoactive constituent, delta-9 tetrahydrocannabinol (delta-9-THC). However, a substantial concentration of CBN acid-A was also present; this compound is unstable to heat and readily undergoes decarboxylation to CBN. Methyl and propyl homologues of CBN, together with delta 9-THC and its naturally occurring acid-A were also found at low concentrations in all samples. Intermediates in the formation of CBN from delta-9-THC, previously identified in aged solutions of the drug, were absent or present in only trace concentrations. However, oxidation products involving hydroxylation at the benzylic positions, C-11 and C-1', not seen in solution, were identified in substantial abundance. The results suggest that decomposition of cannabis samples may proceed more slowly than originally thought. PMID- 2314110 TI - Central nervous system studies on an ethanol extract of Acorus calamus rhizomes. AB - An ethanol extract of Acorus calamus rhizomes was screened for CNS effects using a battery of 20 tests in rats and mice. The extract exhibited a large number of actions similar to alpha-asarone (an active principle of A. calamus) but differed from the latter in several other respects including the responses to electroshock, apomorphine- and isolation-induced aggressive behaviour, amphetamine toxicity in aggregated mice, behavioural despair syndrome in forced swimming, etc. These differences could be due to chemical substances yet to be isolated from the plant extract. PMID- 2314111 TI - A new phytochemical survey of Malaysia. V. Preliminary screening and plant chemical studies. AB - A large phytochemical survey of the flora of the Malaysian Peninsula and Sabah is described, covering the systematic search for alkaloids, and partly, for saponins and flavonoids. Details of some chemical studies are reported. This emphasizes the great interest of such a study. PMID- 2314112 TI - Triple combination of retinoic acid + 6-thioguanine + hexamethylene bisacetamide induces differentiation of human AML blasts in primary culture. AB - Differentiation induction therapy provides an alternative therapeutic approach for patients with acute myeloid leukaemia (AML) who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + 6-thioguanine (6-Th) + hexamethylene bisacetamide (HMBA) on differentiation of blasts from 24 AML patients was studied. Nonadherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in 24-well tissue culture plates containing RPMI-1640 culture medium with 20% fetal calf serum and 10% 5637-conditioned medium and incubated with 10(-6) M retinoic acid, 1.5 X 10(-6) M 6-thioguanine and/or 2 mM hexamethylene bisacetamide for six days at 37 degrees C in a humidified incubator under 5% CO2. Morphological, cytochemical and functional differentiation into mature cells were induced in blasts from 22 out of the 24 AML patients following exposure to the triple combination of 10(-6) M RA + 1.5 X 10(-6) M 6-Th + 2 mM HMBA in primary culture. These effective results justify a clinical trial of such triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. PMID- 2314113 TI - Establishment from an adult leukemic patient of two novel precursor B cell lines with different growth modality. AB - Two novel cell lines, PC-53 and PC-53A were established from an adult ALL patient, at third relapse and in the terminal accelerated phase respectively. Both lines displayed the phenotype of B-cell precursors (CD19+, CD38+, CD20-, cytoplasmic-mu-, immunoglobulin gene rearrangement), identical to the freshly isolated blast cells. Chromosomal analysis showed a prominent 45-XX karyotype, including three marker chromosomes. No chromosome 8 abnormalities were detectable, consistently with a non-rearranged c-myc locus. Both cell lines were EBV-negative. Growth stimulation by autologous supernatant was observed for PC-53 cells during the first 4 months in culture, whereas it was much less evident for PC-53A cells. Thus, PC-53 and PC-53A cells represent a useful tool to investigate the mechanisms involved in the clonal expansion of B-cell precursors. PMID- 2314114 TI - Cytosine arabinoside does not cause differentiation in vitro of CFU-GM in marrow from normal, myelodysplastic or ANLL subjects. AB - This study examines the effect of cytosine arabinoside (Ara-C) on CFU-GM progenitor cells grown in methylcellulose culture from normal and myelodysplastic subjects and patients with acute non-lymphoblastic leukaemia. Light density marrow cells were incubated during culture with Ara-C concentrations ranging from 10(-4) M to 10(-12) M. After counting, colonies were cytospun and cells within the colonies examined for alkaline phosphatase positivity and expression of HLA DR antigen, as indices of differentiation. Monocytes/macrophages were also enumerated in colonies using the monoclonal antibody CD14. In all subjects, 10( 4) M to 10(-6) M Ara-C caused significant reduction in CFU-GM colony formation compared with control (no Ara-C). In no instance did colony numbers increase. Ara C across the dose curve had no effect on myeloid differentiation markers in any of the groups studied. Similarly, percentages of CD14 positive cells in colonies were not altered by exposure to Ara-C. Using this clonogenic model, these data suggest that Ara-C does not induce differentiation of CFU-GM stem cells in normal subjects or patients with myelodysplasia/acute non lymphoblastic leukemia. PMID- 2314115 TI - Immunophenotypical diagnosis and monitoring of hairy cell leukemia. PMID- 2314116 TI - Monoclonal antibody B-ly7: a sensitive marker for detection of minimal residual disease in hairy cell leukemia. AB - The new monoclonal antibody (MoAb) B-ly7 was tested for its value in bone marrow diagnosis in patients with hairy cell leukemia (HCL). Cryostat sections of bone marrow biopsies were examined by an indirect immunoperoxidase technique. Lymphoma cells from all of 26 HCL cases investigated displayed strong surface membrane staining with the MoAb B-ly7, whereas tumor cells from only one of 63 patients with other lymphoproliferative disorders of B cell type reacted with this antibody. The strong reactivity of hairy cells (HCs) with this marker was not altered after therapy as demonstrated on control biopsies taken from patients treated with interferon(IFN)-alpha-2 or 2'deoxycoformycin(DCF) six-64 weeks after start of treatment. This fact as well as the very low number of B-ly7 positive cells found in a series of 13 normal bone marrow biopsies (mean: 0.3% of bone marrow cells, range: 0.0%-1.0%), which could easily be distinguished from HCs by their lower staining intensity and their morphological appearance, provided the basis for the detection of even single HCs. In our hands, in terms of sensitivity the immunohistological detection of HCs using the MoAb B-ly7 was not only superior to classical morphological techniques but also to other immunohistological parameters usually applied for this purpose. Therefore, this MoAb provides a marker for the identification of HCs, hence monitoring disease activity in HCL, and particularly for a critical response evaluation in patients undergoing treatment with IFN-alpha or DCF. PMID- 2314117 TI - Definition of refractoriness against conventional chemotherapy in acute myeloid leukemia: a proposal based on the results of retreatment by thioguanine, cytosine arabinoside, and daunorubicin (TAD 9) in 150 patients with relapse after standardized first line therapy. AB - Response to salvage therapy at first and second relapse was analyzed in 150 patients with acute myeloid leukemia (AML) to improve the characterization of relapsed AML and to deduce from this analysis a proposal for the definition of refractoriness against conventional therapy. Salvage treatment consisted of a repetition of the TAD 9 regimen which was already applied as induction protocol at initial diagnosis. All patients were recruited from the multicenter 1982 trial of the German AML Cooperative Group and had thus received a standardized first line treatment. Response at first relapse was significantly related to the duration of the first remission. From 38 patients relapsing within 6 months after successful induction therapy, only 11 (28%) achieved a second complete remission as compared to 58 of 98 (59%) cases with later occurring relapses (p less than 0.01). This difference was due to a significantly higher incidence of persistent leukemia in the former group and not biased by differences in early death rates. No other variable was found predictive for the response to salvage treatment including age, WBC, serum LDH, morphologic subtype, presence or absence of DNA aneuploidy as detected by flow cytometry or maintenance chemotherapy. A low remission rate of 28% was also obtained in the 14 patients at second relapse. These data indicate that patients with a duration of their first remission of more than 6 months cannot be considered as being refractory against standard chemotherapy while patients with early relapses and second recurrences have a response rate of less than 30% due to refractory disease. Hence, the following criteria are proposed for the definition of refractoriness against standard chemotherapy in advanced AML: (a) nonresponse to first-line induction therapy, (b) early relapse within 6 to 12 months of first remission, (c) relapse after 6 to 12 months of first remission and failure on a reinduction attempt with established regimens, (d) second and subsequent relapses. These criteria may provide a useful rationale for the selection of the most appropriate treatment at relapse. They may also serve as eligibility criteria for clinical phase I/II studies and will facilitate interstudy comparisons. PMID- 2314119 TI - Characteristics of the leukemic cell in childhood acute lymphoblastic T cell leukemia at diagnosis. PMID- 2314118 TI - Continuous infusion diaziquone and etoposide: a phase I study in adult patients with acute leukemia. AB - Diaziquone (AZQ) and etoposide (VP-16) were administered as simultaneous 5-day continuous infusions to 27 patients with acute leukemia (22 with acute myeloid leukemia (AML), three with chronic myeloid leukemia in blast crisis (CML-B), and two with acute lymphocytic leukemia) at four different doses in a phase I trial. Gastrointestinal toxicity, primarily stomatitis, was dose limiting, occurring in six of 10 patients at the highest dose level. Diarrhea was the only other grade 3 toxicity noted (three of 10 at the highest dose level). The duration of bone marrow aplasia was excessive at the highest dose (median 48 days to granulocytes greater than 500/mm3, range 33-67) but acceptable (31 days) at the maximum tolerated dose: AZQ 28 mg/m2/day x 5 days, VP-16 150 mg/m2/day x 5 days. Complete remissions were seen in seven patients (six AML, one CML-B) and a partial remission in one patient with AML. The median duration of unmaintained complete remission was 3 months (range 1.5-26+). PMID- 2314120 TI - AcSDKP, an inhibitor of CFU-S proliferation, is synthesized in mice under steady state conditions and secreted by bone marrow in long-term culture. AB - The peptide AcSDKP, isolated from fetal calf bone marrow, is able to prevent DNA synthesis in mouse CFU-S in vivo and in vitro. The molecule is demonstrated here to be constitutively produced in mice and synthesized by bone marrow cells in long term culture. PMID- 2314122 TI - Pediatric reference intervals for 19 biologic variables in healthy children. AB - We defined age- and sex-specific reference intervals for 19 biologic variables in serum samples from healthy children, 1 to 22 years of age, using common laboratory equipment. Upper and lower reference intervals were defined as the estimated 2.5 and 97.5 percentiles of the distribution. For variables (y) that varied with age, the relationship of y to age was modeled with polynomial regression. Parametric percentile estimates specific to each age were then calculated as the predicted y value +/- 1.96 . SD, in which SD = the standard deviation of the residuals. For variables not associated with age, the nonparametric 2.5 and 97.5 sample percentiles were used to define the reference intervals. No significant age or sex differences were found for serum sodium, total protein, glucose, direct bilirubin, or albumin. Potassium, chloride, and urea showed constant values in children that were higher than adult values in the case of potassium and chloride and lower than adult values in the case of urea. No sex-related differences were seen for these analytes. Creatinine, uric acid, and bicarbonate showed an upward trend in values with increasing age, whereas aspartate aminotransferase, phosphorus, and total and ionized calcium showed a downward trend with increasing age. Sex-related differences were noted for these analytes. The immunoglobulins (IgG, IgA, and IgM) showed an upward trend with increasing age, with no sex-related differences except for IgM in children. PMID- 2314121 TI - Adrenal medullary transplantation into the brain for treatment of Parkinson's disease: clinical outcome and neurochemical studies. AB - Transplantation of adrenal medulla into the caudate nucleus as treatment for Parkinson's disease was performed in eight patients. Although our previous 6 month follow-up revealed early modest improvement, an extension of that follow-up to 1 year disclosed no additional gains in any patient. At the end of 1 year, only one patient could be categorized as moderately improved; three patients were mildly improved, and four patients were unimproved. The rationale for transplanting adrenal medulla was to reestablish a physiologic source of dopamine to the striatum. We measured cerebrospinal fluid (CSF) and plasma catecholamines and metabolites before and after transplantation. Conjugated dopamine (the predominant form of dopamine found in the CSF) and homovanillic acid (the major dopamine metabolite) were modestly and inconsistently increased in the CSF. Conjugated and free epinephrine and norepinephrine, as well as 3-methoxy-4 hydroxyphenylglycol concentrations were not increased in CSF after graft placement, an indication that the adrenal chromaffin cells were no longer producing high levels of these nondopamine catecholamines and metabolites. CSF cortisol concentrations were not increased after transplantation, compared with values from controls, consistent with low numbers of functioning adrenal cortical cells contaminating the graft (or poor survival). Posttransplantation CSF did not induce a neurotrophic effect in cell cultures of 15-day embryonic rat dorsal root ganglion or PC12 (rat pheochromocytoma) cell lines. Survival of samples of patients' adrenal medullary tissue for 2 weeks in tissue culture attested to the viability of the graft at the time of transplantation. The relative concentrations of dopamine to epinephrine or norepinephrine increased in these cultured adrenal medullary cells, presumably because of loss of the glucocorticoid influence on catecholamine synthesis. A wide variety of factors could have contributed to our failure to replicate the earlier impressive results of adrenal-to-brain transplantation reported by others. Continued transplantation studies in animal models of parkinsonism are necessary for better elucidation of these factors. PMID- 2314123 TI - Evaluating the effect of a human values seminar series on ethical attitudes toward resuscitation among pediatric residents. AB - A human values seminar series was designed to provide training in medical ethics for residents in pediatrics. Attitudes of residents toward resuscitation of children were surveyed before and after the seminar series. Nonpediatric residents rotating through pediatrics served as control subjects. Although both groups of residents demonstrated a significant change in attitude on six scales at the end of 1 year of training, pediatricians and nonpediatricians differed from each other with respect to only one of these scales. After the seminar series, pediatric residents expressed decreased willingness to resuscitate certain critically ill infants in the emergency room, whereas nonpediatricians expressed more willingness (P less than 0.009). Attitude change in decision making among pediatricians was significantly correlated with the consideration given to societal needs, sanctity of life, and anticipated poor morbidity (P less than 0.05). Among nonpediatricians, attitude change was significantly correlated with poor prognosis for survival (P less than 0.05), morbidity (P less than 0.05), or anticipated poor intellectual outcome (P less than 0.01). Attitude differences between the two groups of residents were unrelated to differences in preexisting attitudes or demographic factors. These findings show that attitudes about ethical decisions are influenced by both "maturation," or progression through a training program, and formal instruction. The finding that clinical attitudes change rapidly as residents progress through training confirms our previous findings and suggests that residency training programs should provide support and formal instruction in ethics during this time of change. The small change caused by this current method of instruction indicates that preliminary studies are needed to delineate the goals and the structure of future ethics courses. PMID- 2314124 TI - Reference values in pediatric medicine. PMID- 2314125 TI - Helicopter medical transport service. PMID- 2314127 TI - Isolation and identification of aging-related cDNAs in the mouse. AB - To identify genes whose expression changes as a function of aging, we screened mouse cDNA libraries with cDNAs from mice of different ages. Specifically, whole mouse cDNA libraries were constructed in lambda gt10 using poly(A) RNA from young (3 month) and old (27 month) C57BL/6J inbred mice and these lambda plaques were hybridized with radioactive cDNAs made from pooled poly(A) RNA from animals 3 or 33 months of age. Five clones were isolated that showed an aging-related pattern of expression and four of these were identified by computerized sequence matching to the GenBank database: MUP2 (a major urinary protein); Q10 of the MHC locus; a cytoskeletal actin gene; and creatine kinase. One gene whose expression increases with aging and is most abundant in spleen remains unidentified. All five cDNAs showed 4-fold to 17-fold changes with aging in their steady-state mRNA levels in at least one tissue. PMID- 2314126 TI - Effect of aging on pulmonary superoxide dismutase. AB - Pulmonary Cu,Zn superoxide dismutase was examined in young (1-month-old), adult (4-5-month-old) and aged (24-months-old) rats to determine if partially inactive forms of the enzyme accumulate in the lung with age. Measurement of Cu,Zn superoxide dismutase activity in lung homogenates showed that total Cu,Zn superoxide dismutase activity/mg DNA was essentially the same in adult and aged rats. The average value of Cu,Zn superoxide dismutase/mg DNA for young rats was less than half that of adult and aged rats. Cu,Zn superoxide dismutase was purified from the lung homogenates and fractionated into isoelectric variants by either isoelectric focusing or chromatofocusing. Three main isoelectric variants of Cu,Zn superoxide dismutase were recovered with pI values of 5.15, 4.88 and 4.75. In all age groups studied, the pI 4.88 variant had a markedly higher specific activity than the other two variants, as well as the highest metal content and greatest resistance to inactivation of all three variants. The pI 4.88 variant declined from 88% of the total Cu,Zn superoxide dismutase activity in the young animals to only 70% in the aged animals. The results of this study indicate that the proportion of the relatively inactive forms of pulmonary Cu,Zn superoxide dismutase increased with age. PMID- 2314128 TI - The effect of chronic apomorphine treatment on the ultrastructure of the prolactin cells and on plasma prolactin levels in young and aged male Wistar rats. AB - Effects of two doses of apomorphine on the plasma prolactin (PRL) levels and on the ultrastructure of PRL cells in young and aged male Wistar rats were investigated. In young and aged control rats no significant differences were found between the plasma PRL levels. Immunocytochemical staining with anti-r-PRL revealed significant differences between young and aged control rats; in young rats the number of PRL cells with polymorphic granules exceeded the number of cells with round granules, whereas in aged rats almost exclusively cells with round granules were found. In young rats, chronic treatment with a low dose (0.01 mg/kg/day) of apomorphine did not result in a significant change in plasma PRL level or cell morphology. However, high dose (0.25 mg/kg/day) of apomorphine resulted in a significant decrease in plasma PRL levels, a decrease of number of cells with polymorphic granules and an increase of cells with round granules. The occurrence of PRL cells with round granules and plasma levels was negatively correlated. In aged rats, apomorphine (0.01 or 0.25 mg/kg/day) treatment did not affect plasma levels nor did it affect the distribution of the cell types. We conclude that in young rats PRL cells are sensitive to apomorphine and that their ultrastructure reflects a phase of the secretory cycle. In aged rats, the cells appear to have lost their sensitivity to apomorphine. The fact, that the distribution over the different cell types in control aged rats is similar to that of the apomorphine-treated young rats, suggests a strong influence of endogenous dopamine on PRL cell physiology in the aged rat. PMID- 2314129 TI - Mitogen-activation of spleen cells in aged animals is potentiated by dietary restriction: a preliminary report. AB - Dietary restriction has been reported to be associated with increased life span and increased DNA repair capacity in both male and female rats and mice. We examined dietary restriction effects on immune system function and prolongation of life span in specific pathogen free rats and mice. In this preliminary report the authors show that dietary restriction is correlated with a dramatic increase in the lifespan of both male and female rats and mice in a pathogen free environment, and in the capacity of cultured splenocytes from those animals to initiate blastogenesis in response to antigenic stimulation. PMID- 2314130 TI - Action of potassium on neurochemical transmission at the cardiac adrenergic neuroeffector junction with aging. AB - The effect of age on potassium (K+)-induced norepinephrine release in the heart was studied in 6- and 24-month-old male Fischer-344 rats. Isolated hearts were perfused with Krebs-Ringer solution according to Langendorff method. K+ was employed as 2 ml bolus at the concentrations, of 70, 90, 100 and 120 microM. Norepinephrine content was measured by high pressure liquid chromatography/electrochemical detection methodology. At each of the K- concentrations, the amount of norepinephrine released from preparations of 6 month-old animals was significantly greater than observed from preparations of 24 month-old animals. Since K(+)-induced release of norepinephrine is associated with calcium influx, the decrease in the capacity of K+ to cause norepinephrine release with age supports the hyothesis that diminution in transmitter release is due to altered calcium function. PMID- 2314131 TI - Accumulation of cardiac lipofuscin in mammals: correlation between sexual maturation and the first appearance of lipofuscin. AB - Accumulation of lipofuscin is an important phenomenon of the cellular aging process. The first appearance of cardiac lipofuscin showed a good correlation with sexual maturation, which was correlated with maximum life-span of mammals. Large metabolic changes occurred at sexual maturation. From these results, it is suggested that sexual maturation of mammals is the initiation period of the aging process. Correlation between sexual maturation and longevity was re-evaluated using many mammals. Domestic and laboratory animals showed an earlier sexual maturation than other mammals, including rodents. PMID- 2314132 TI - The Rand Health Insurance Experiment and HMOs. AB - The Rand Health Insurance Experiment (HIE) provides the most persuasive evidence to date on the relative effects of health maintenance organization (HMO) and fee for-service care on utilization, costs, client satisfaction, and health care outcomes. Publications from the HIE have suggested that HMO care was associated with lower costs because of reduced hospitalizations, lower client satisfaction, and poorer health status among the subgroup with limited incomes and initial health status. In our view, the evidence justifies the conclusions related to utilization, costs, and satisfaction, but not the suggestion that HMO care had adverse health effects on low-income, sick individuals. PMID- 2314133 TI - Simulated effects of incomes-based policies on the distribution of physicians. AB - As the United States enters a period of adequate physician supply (or even surplus), policies to ameliorate the maldistribution of physicians across communities and medical specialties will depend more heavily on explicit redistributional incentives. Targeted financial incentives are an obvious method for encouraging desirable practice choices. This paper simulates the effect of a series of incomes policies on the distribution of sample physicians across specialties, community sizes, and practice modes. The predictions are based on the estimated parameters of a simultaneous choice model for these three dimensions of a physician's practice. The results suggest that policies based on financial incentives are more effective than previous research has indicated. PMID- 2314134 TI - Physician contact with and attitudes toward HIV-seropositive patients. Results from a national survey. AB - The growing population of HIV-seropositives raises serious concerns about who will provide medical care to this group. This article presents the first national estimates of physician involvement in, and attitudes toward, the treatment of HIV seropositive patients. Nearly 50% of the nonfederal patient care physicians in our nationally representative sample have treated at least one HIV patient, with an average of 6.7 such patients being treated per physician. Perceived responsibility to treat HIV-seropositive patients is uniformly strong across such physician and practice characteristics as specialty, years of experience, and practice type. However, there are pronounced differences in actual physician involvement along these dimensions. PMID- 2314135 TI - Older patients' health status and satisfaction with medical care in an HMO population. AB - Few studies have examined the relationship between older patients' satisfaction with medical care and their health status, and none of these investigations has been based at an HMO. To examine this question, data on 532 patients older than 70 years in an HMO were analyzed. Patients' reports of satisfaction with medical care were examined in relation to several dimensions of health status (based on self-reports, chart data, and physicians' ratings), their own sociodemographic characteristics, and characteristics of their primary physicians. Greater satisfaction was significantly associated with better self-rated health and physical function, less emotional distress, and more social activity but was not related to physicians' health ratings, number of diagnoses, or cognitive function. Mean levels of satisfaction were also significantly different for patients of different physicians but not appreciably related to patients' sociodemographic characteristics. When patient sociodemographic characteristics were controlled for, the relations of health status variables to satisfaction were essentially unchanged. It was concluded that the key issues to be resolved are whether better health leads to greater satisfaction or vice versa, and, in either case, whether the relations are mediated by factors relating to the patient's experience of medical care. PMID- 2314137 TI - [The transtracheal catheter: an open door to modern continuous oxygen therapy at home]. PMID- 2314136 TI - Impact of geriatric nurse practitioners on nursing-home residents' functional status, satisfaction, and discharge outcomes. AB - This study evaluated the impact of geriatric nurse practitioners (GNP) employed by nursing homes on quality of patient care and residents' outcomes during a 12 month study period. Quality of care was assessed in standardized interviews of 525 residents in five nursing homes with GNPs and 323 residents in five other nursing homes without GNPs. Each resident was interviewed up to four times during the study period (at baseline, and 3, 6, and 12 months later) to determine functional status, satisfaction with care, and physical condition at each of these points. The only significant difference between groups was that fewer newly admitted residents were hospitalized from GNP homes than from those without a GNP. The results of this interview study showed that the GNP as a nursing home employee had little impact on residents' functional status, physical condition, or satisfaction. PMID- 2314138 TI - [Pseudomonas aeruginosa infection following ventriculo-peritoneal shunt]. PMID- 2314139 TI - [Non-ketoacidic hyperosmolar diabetic decompensation caused by hyperthyroidism. An infrequent fact]. PMID- 2314141 TI - [Polymicrobial bacteremia at intensive care units]. PMID- 2314140 TI - [Attitudes of specialized health personnel regarding the human immunodeficiency virus disease]. PMID- 2314142 TI - [Hepatic veno-occlusive disease in a patient undergoing bone marrow autotransplant after busulfan and melphalan conditioning]. PMID- 2314143 TI - [A campaign for detection of beta-thalassemia minor and prevention of beta thalassemia major in the island of Minorca. 2 years' experience]. AB - The high prevalence of beta-thalassemia minor and the occurrence of thalassemia major in Minorca prompted us to develop a prevention campaign. The selected population consisted of primary school students. The campaign was operative during the terms 1986-87 and 1987-88 and had three stages: 1.) informative; 2.) analytical study and diagnosis of carriers; 3.) report of the results and genetic counselling. We studied overall 1862 schoolchildren. The prevalence of beta thalassemia minor was 3.38%. We discuss the methodology, the results and the effectiveness of the campaign. PMID- 2314144 TI - [Treatment of acromegaly. Results in 56 patients]. AB - The results of the treatment of acromegaly in 56 patients have been reviewed. Transsphenoidal pituitary adenomectomy (TPA) represented the most effective therapy, as it resulted in a cure rate of 64.7%, with 8.8% of complications and 14.7% of endocrine insufficiencies secondary to surgery. When radiotherapy was administered after surgery (when the latter had not been curative), the overall rate of cure increased to 73.5%. By contrast, the patients treated only with radiotherapy had a markedly lower cure rate (44.4%), with a higher rate of endocrine insufficiency (55%). The occurrence of extrasellar extension shown in preoperative pituitary computed tomography did not correlate with a worse postoperative cure rate; by contrast, the invasive character of the adenoma represented a reduction in the postoperative cure rate. It was concluded that TPA is the treatment of choice in acromegaly, independently of the tumor size. PMID- 2314145 TI - [Peripheral tuberculous arthritis in Galicia]. AB - We have evaluated the cases of tuberculous arthritis in peripheral joints (TAPJ) that had been diagnosed in our unit during the last twelve years. The diagnosis was made by synovial biopsy in 26 of 33 cases, and by synovial fluid culture in the remaining 7. TAPJ accounted for 2.4% of all forms of tuberculosis and for 6% of extrapulmonary cases diagnosed in our hospital during those years. In 54% of cases there were risk factors of tuberculous infection. The mean time from the onset of symptoms to the confirmation of the diagnosis was longer than one year. All cases had clinical features of monoarthritis, and the knee was the most commonly involved joint (42%). In the 16 investigated synovial fluids the mean cellular rate was 11060 cells/mm3. The most reliable diagnostic procedure was the histological confirmation with synovial biopsy, whereas the yield of synovial culture was 64% and that of staining techniques 40%. In 97% of cases the treatment was effective. Orthopedic surgery was required in 36% of cases, and 48% had sequelae. PMID- 2314147 TI - [Hematopoietic growth factors]. PMID- 2314146 TI - [Health information of intercontinental Spanish travelers]. AB - To investigate the level of health information and degree of protection of Spanish travelers to tropical and temperate zones, 910 individuals were interviewed in the Prat del Llobregat airport before their departure. Very low levels of protection were detected, regarding both compulsory and optional vaccines as well as antimalarial protection. It was found out that the information sources that had been consulted were not the optimal ones and that they had delivered remarkably inaccurate advice. Only 44% had received some type of vaccination. Important geographic errors were recorded regarding vaccination against yellow fever. Few travelers received optional vaccines, although these provide protection against highly prevalent diseases in tropical areas. Errors in antimalarial chemoprophylaxis were related both to drug dosage and their adequacy to the corresponding areas. Travelers prematurely interrupted prophylaxis in a progressive fashion depending on the number of elapsed weeks. Only 33% of the 39% who started prophylaxis before leaving completed it correctly. Travelers from health care professions had a higher rate of early abandonment of antimalarial prophylaxis and a worse immune protection against yellow fever, with a 5% signification level (p less than 0.05) when compared with the rest of travelers. Suggestions to improve this situations are made, such as an adequate education of health professionals and the general population, the reshaping of official vaccination centers and the introduction of adequate antimalarial drugs in the Spanish pharmacopeia. PMID- 2314148 TI - Antinociceptive activity of intracisternally and intrathecally administered eptazocine, a novel analgesic, in mice. AB - Antinociceptive potency of eptazocine (1-1,4-dimethyl-10-hydroxy-2,3,4,5,6,7 hexahydro-1,6-methano-1H-4-ben zazonine), a novel analgesic derived from homobenzomorphan, was compared with that of morphine and pentazocine after intracisternal and intrathecal administration into conscious mice using acetic acid-induced writhing, tail pressure and hot plate tests. The rank order of potency for inhibition of writhing after intracisternal administration was morphine greater than eptazocine greater than pentazocine. In contrast, the intrathecal compounds inhibited writhing with a rank order of potency of eptazocine greater than or equal to morphine greater than pentazocine. On the tail pressure and hot plate tests after intrathecal administration, ED50 ratios of eptazocine to morphine were much smaller than that on the writhing test. Systemic naloxone did not antagonize the antinociceptive effect of intrathecal eptazocine on the writhing test. These results suggest that the antinociceptive action of eptazocine is rather specific to chemical nociceptive stimuli and may be mediated via spinal non mu-opioid receptors in the mouse. PMID- 2314150 TI - The differential effects of post-session administration of amineptine and imipramine on memory processes in mice. AB - The effects of post-trial administration of amineptine, a dopaminergic antidepressant drug, were compared with those of memory-facilitating (strychnine, piracetam) or impairing drugs (phenobarbital, imipramine) on an experimental model of memory. Mice were given two sessions in open-field test and the decrease in activity at the second session (habituation) served as an index of retention. The good retention observed with a 1-day inter-session interval was impaired by post-session administration of phenobarbital (10 mg/kg i.p.) or imipramine (5.0 mg/kg i.p.). The poor retention observed with a 5-day inter-session interval was enhanced by post-session administration of strychnine (0.20 mg/kg i.p.), piracetam (1000 mg/kg i.p.) and amineptine (10 mg/kg i.p.). These findings show that different profiles of cognitive and psychomotor effects were produced by imipramine and amineptine. Amineptine, lacking sedative and anticholinergic properties which are characteristic of imipramine, interferes positively with learning and memory, in a manner similar to piracetam and strychnine. PMID- 2314149 TI - The protective effect of adenosinergic agents, Ro 5-4864 and carbamazepine against hypoxic stress-induced neurotoxicity in mice. AB - Mice subjected to hypoxic stress resulted in increased respiratory rate, tremor and convulsions followed by death. The latencies for convulsion and death following hypoxic stress were 33.29 +/- 1.20 and 34.36 +/- 1.16 min, respectively. In the present study effects of adenosinergic agents Ro 5-4864, a "peripheral-type" benzodiazepine receptor agonist, and carbamazepine were studied on hypoxic stress-induced neurotoxicity. Adenosinergic agents such as adenosine, 2-chloroadenosine, N6-cyclohexyladenosine and dipyridamole increased the latencies for convulsions and death due to hypoxia. Theophylline (50 mg/kg i.p.), an adenosine receptor antagonist, reversed this protective effect of adenosinergic agents. Pretreatment with Ro 5-4864 (10, 20 mg/kg i.p.) also offered theophylline (50 mg/kg, i.p.)-sensitive protection against hypoxic stress. Similarly, carbamazepine treatment (10-30 mg/kg, i.p.) significantly prolonged the latencies for convulsion and death following hypoxic stress. Prior treatment with theophylline (50 mg/kg, i.p.) reversed this protective effect of carbamazepine, indicating the possible involvement of adenosinergic mechanism in the observed protective effect of carbamazepine. These results indicate that the adenosinergic mechanism may be responsible for the observed neuroprotective effect of these agents against hypoxia. PMID- 2314151 TI - Antagonism of fentanyl-induced respiratory depression with nalmefene. AB - We determined the ability of a new opioid antagonist, naimefene, to prevent fentanyl-induced respiratory depression in 8 healthy male volunteers. Ventilation and pulmonary function were measured with the respiratory inductive plethysmograph (RIP), which is non-invasive and requires no connection to the airway. Each volunteer was tested two times on different days. During the first session, each volunteer was monitored for one hour of baseline measurement followed by 4 hourly injections of fentanyl (1 microgram/kg) administered in an open-label manner. In the second session, the subjects were monitored for one hour after 1 mg of intravenous nalmefene was administered. Intravenous fentanyl or identical placebo were then given in a double-blind manner as in the first session. Progressive and profound respiratory depression occurred with fentanyl administration alone. In the absence of nalmefene, fentanyl converted normal breathing pattern to an irregular breathing pattern. When the subjects were treated with nalmefene prior to fentanyl administration, all of these changes were almost completely prevented. Pulmonary variables which reflected this difference between the fentanyl-alone group and the nalmefene-pretreated groups included frequency (p less than 0.001), tidal volume (p less than 0.001), percent rib cage contribution to tidal volume (p less than 0.001) and expiratory time (p less than 0.001). This study showed that nalmefene is an effective long-acting opioid antagonist, and that RIP accurately measures changes in respiration caused by opioid administration. PMID- 2314152 TI - Ion-trapping of meperidine: influence of antacid treatments on serum and gastric fluid concentrations. AB - The ascorbic acid pretreated beagle dog was used to demonstrate the phenomenon of ion-trapping and the influence of three different antacid treatments on the serum and gastric fluid concentration of meperidine: pretreatment with magnesium aluminum hydroxide (MA), pretreatment with cimetidine (C), and periodic total aspiration of gastric fluid (ASP). A significant correlation between pH and the meperidine concentration in gastric fluid was found; the lower the pH the higher is the secretion of meperidine into gastric fluid. The gastric fluid meperidine concentrations were 8-30 times as high as the respective serum concentrations. No significant differences between the meperidine concentration in the gastric fluid were found among the three treatments, MA, C, or ASP, versus control. Meperidine serum concentrations differed significantly versus control on two times for MA and on one time for ASP. The elimination half-life [h] and the mean residence time [h] differed significantly in the MA treatment (1.15 +/- 0.02 h and 1.23 +/- 0.24 h) versus control (1.90 +/- 0.19 h and 2.00 +/- 0.15 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314154 TI - Disposition of pethidine in man under acidic urinary pH. 4. Kinetics after oral dose in caucasian, Chinese and Indian subjects. AB - The pharmacokinetics of low dose pethidine (450 micrograms kg-1) after oral administration were determined in 9 Caucasian, 9 Chinese and 9 Indian healthy volunteers under conditions of acidic urinary pH. Plasma and urine concentrations of pethidine and norpethidine were determined simultaneously by gas liquid chromatography. In all three ethnic groups the oral absorption of pethidine was rapid. The Tmax was faster in the Caucasian group (0.75 h) compared with the Chinese group (1.0 h) and the Indian group (1.5 h). No significant difference was observed in their respective lag time while the absorption t1/2 was significantly shortest in the Caucasian group who also had the highest Cmax (95.5 +/- 7.8 ng ml 1) compared with the Chinese (85.9 +/- 11.0 ng ml-1) and the Indian (58.2 +/- 3.0 ng ml-1) groups. Moderate exercise and upright posture of the Asian students might interfere with absorption and distribution of pethidine, due possibly to change in blood flow during the early stage of the study while the Caucasian subjects were in supine position. No significant difference was observed in the elimination t1/2 of pethidine between the Caucasian (8.3 +/- 0.2 h) and the Chinese (8.2 +/- 0.2 h) groups, although the Indian subjects significantly had the longest elimination t1/2 (0.1 +/- 0.3 h); this could possibly be due to their significantly higher apparent volume distribution. Under acidic urinary conditions both Chinese and Indian subjects excreted significantly more norpethidine in the urine while no difference was observed in the recovery of unchanged pethidine; this may suggest an interethnic difference in the oxidative demethylation of pethidine. PMID- 2314153 TI - Binding of thiopental to human serum albumin in the presence of halogenated hydrocarbons and ethers. AB - Thiopental binding (substrate concentration 0.04.10(-3) M = 10 micrograms/ml) to 1% human serum albumin (HSA) studied by equilibrium dialysis in 1/15 M phosphate buffer solution (pH 7.4) was increased significantly from 40.2% (= control) to 55% in the presence of 4.71.10(-3) M halothane (= 11.36 vol%); 1.18.10(-3) M = 2.84 vol% halothane caused a lesser but still significant increase (vs. control) of thiopental binding. This halothane effect on the binding of thiopental to HSA was studied under several experimental conditions (variation of thiopental concentration, HSA concentration, pH of the buffer solution, temperature). Other halogenated hydrocarbons such as chloroform (6.2.10(-3) M) and carbon tetrachloride (5.2.10(-3) M) also markedly increased the binding of thiopental to HSA as compared to the control (percentage of fraction bound, 53 and 61%, respectively); the same effect, but to a lesser extent, was obtained under the influence of three halogenated ethers, i.e., enflurane (4.1.10(-3) M--greater than 45% thiopental bound), isoflurane (4.1.10(-3) M--greater than 50% bound) and methoxyflurane (4.3.10(-3) M--greater than 47% bound). Under the same experimental conditions, ethanol (up to 8.9.10(-2) M) and diethylether (up to 4.9.10(-2) M) did not increase the percentage of thiopental bound to HSA. PMID- 2314155 TI - [Travellers' diarrhea--prevention, self-care or no measures at all? Antibiotics only for at-risk groups and a small number of travellers]. PMID- 2314156 TI - [Misuse of psychiatry within health services--a sign of wrong diagnosis?]. PMID- 2314157 TI - [Spontaneous pneumothorax: consideration of background factors is more important than length of treatment]. PMID- 2314158 TI - [A case of familial hypercholesterolemia with therapeutic difficulties]. PMID- 2314159 TI - [Prolonged survival after bone marrow transplantation in patients older than 30 years of age]. PMID- 2314160 TI - [Barrett esophagus--diagnosis and therapeutic strategy]. PMID- 2314161 TI - [Ethical thinking should have a central position in professional nursing care]. PMID- 2314162 TI - [What can we learn from the ferryboat accident in Zeebrugge? To be well prepared is the best way to meet disasters]. PMID- 2314163 TI - [Homeopathy must be made a university subject]. PMID- 2314164 TI - [Legal regulation of Chlamydia infections restores order at a chaotic department]. PMID- 2314165 TI - [Frequent problems and acutely affected lungs in dock workers unloading grain]. PMID- 2314167 TI - [The computer sabotage of AIDS research: it is easy to clear a contaminated computer. Still not known who caused the coup]. PMID- 2314166 TI - [Sleep apnea syndrome patients can in many cases get relief through surgery]. PMID- 2314168 TI - [Health of the elderly--care or health service]. PMID- 2314169 TI - [Important everyday rehabilitation--a responsibility of the leadership]. PMID- 2314171 TI - [Patients free choice of health services can be connected with continuous health care]. PMID- 2314170 TI - [Who should staff our ambulances?]. PMID- 2314172 TI - [To operate or not, that is the question]. PMID- 2314173 TI - [Research on pathological hair loss must proceed]. PMID- 2314174 TI - [The patient, the doctor, Chlamydia law and reality]. PMID- 2314176 TI - [The kangaroo method is a good complement to traditional incubator care]. PMID- 2314175 TI - [Amalgam clearing in mercury poisoning]. PMID- 2314177 TI - [The 1987 questionnaire: increased use of arterial surgery but with significant regional differences]. PMID- 2314178 TI - [Decreased numbers of placental retention after oxytocin compared to methylergometrin]. PMID- 2314179 TI - [One-year experience with coronary angioplasty in Umea. Adequate training and planning are behind the good results and high capacity]. PMID- 2314180 TI - [Most patients attitude is positive to a new, reconstructed nipple in connection with mastectomy]. PMID- 2314181 TI - [Lichen sclerosus et atrophicus in children can be misinterpreted as sexual abuse]. PMID- 2314182 TI - [Tuberculous infection of the symphysis]. PMID- 2314183 TI - [The camp in Khao I Dang is a symbol of escape and hope]. PMID- 2314184 TI - [Age as a priority factor--are not all equally entitled to health care services?]. PMID- 2314185 TI - [Complications in 39,397 endoscopic studies--a 7-year prospective documentation on method and incidence]. AB - All complications of diagnostic and therapeutic endoscopic procedures from Feb. 1, 1982, to Jan. 31, 1989, at the Medical Department I of the Ludwigsburg hospital were reviewed. Complications occurred in 0.02% of all esophago gastroduodenoscopies, in 0.09% of all endoscopic retrograde cholangio pancreaticographies and in 0.05% of all colonoscopies. Rectos-copies and laparoscopies have to date been performed without complications. For therapeutic endoscopic procedures, the incidence of complications varies depending on the type of procedure performed. In 1.2% of gastric polypectomies, in 0.52% of colonic polypectomies and in 2.22% after endoscopic papillotomy complications occurred. In summary, both diagnostic and therapeutic endoscopy with adequate training can be considered as very safe procedures and only rarely leading to complications or death. PMID- 2314187 TI - [Primary non-Hodgkin lymphoma of the stomach: diagnostic and therapeutic procedure]. AB - It is reported on 13 patients with gastric non-Hodgkin's lymphoma, who underwent surgery between Jan 1st, 1984, and Sept 1st, 1987. Common symptoms included abdominal pain, weight loss and decline in health and strength. Endoscopy or barium studies had established the diagnosis of a gastric neoplasma in 12 cases. A total gastrectomy (n = 4) or a distal resection (B I n = 3, B II n = 5) was performed, depending on the size of the tumor and its location. Potentially curative resection was followed by radiotherapy in patients with high-grade lymphoma (stage I E). Patients with involvement of regional lymph nodes and advanced gastric lymphoma (stage II E1-IV E) underwent postoperative chemotherapy. So far follow-up (mean 25.3 months) revealed one case of relapse. These results confirm the value of surgical treatment in diagnosis, staging and treatment of primary gastric lymphoma. Survival in patients with advanced lymphoma and high-grade malignancy can be improved significantly by radical tumor resection, followed by multiagent chemotherapy and radiation. PMID- 2314186 TI - [Use of the stable nitrogen isotope 15N in assessing liver metabolism in hormonal contraception]. AB - In 37 women with long-term use of oral contraceptives (average use 13.4 years) and 12 women who had not taken oral contraceptives for at least 5 years we determined the serum enzymes ALAT, ASAT, Gamma-GT and conducted the 15N-ammonium test as a marker of partial metabolic performance of the liver. In addition we studied total protein, protein fractions in the serum and haematologic parameter. 18 out of 37 women showed a morbid result in the 15N-ammonium test. In 4 of these 18 women morphological changes representing hepatic damage caused by contraceptives could be detected. On the average ALAT, Gamma-GT and 15N-ammonium test in both groups are clearly different. Because the enzymic levels are being in the normal range, only the 15N ammonium test enables to give a hepatotoxic evidence. It is possible to conclude that long-term use of oral contraceptives influences the liver metabolism. PMID- 2314188 TI - [News on TNM consultation activity of the German Language Committee]. PMID- 2314189 TI - Retrograde amnesia produced by intrastriatal atropine and its reversal by choline. AB - A number of studies have shown that cholinergic blockade of the striatum produces amnesia. In the present experiment it was predicted that by increasing the synthesis of striatal acetylcholine such amnesic state would be prevented. Atropine was injected into the striatum of rats before training of passive avoidance; some of these rats were also injected, intrastriatally, with choline before testing the retention of the task. Atropine alone produced amnesia while the combination of treatments reversed this effect. PMID- 2314190 TI - Amniotic-fluid ingestion by parturient rats enhances pregnancy-mediated analgesia. AB - Amniotic fluid and placenta contain a substance (POEF, for Placental Opioid Enhancing Factor) that, when ingested, enhances opioid-mediated analgesia in nonpregnant rats; ingestion of the substance by rats not experiencing opioid mediated analgesia, however, does not produce analgesia. It is highly likely that periparturitional analgesia-enhancement is a significant benefit of ingestion of the afterbirth (placentophagia) during delivery. Here we report that prepartum ingestion of amniotic fluid (via orogastric infusion) does indeed enhance the endogenous-opioid-mediated analgesia evident at the end of pregnancy and during delivery; that the degree of enhancement is greater with 0.75 ml than with 0.25 ml; and that the prepartum enhancement of analgesia can be blocked with the opioid antagonist naloxone. PMID- 2314191 TI - Role of angiotensin II and vasopressin in cisplatin-induced emesis. AB - Cisplatin-containing chemotherapy regimens are known to produce intense nausea and vomiting. Angiotensin II (AII) and vasopressin (AVP) have been shown to have emetic properties. The role of these two peptides on cisplatin-induced vomiting was investigated in beagle dogs. Cisplatin (2 mg/kg, IV over 5 min) produced consistent emesis in all dogs after a mean latency time of 144 +/- 4 min. Serum Angiotensin Converting Enzyme (ACE) and plasma AII levels did not significantly change 3 hr after cisplatin administration (at the time of nausea and emesis) in control animals. AVP levels rose from 0.3 pg/ml to 7.5 pg/ml 3 hrs after cisplatin. Complete inhibition of ACE with enalapril (given at 3 mg/kg p.o., 3 hrs prior to cisplatin) reduced AII levels by 70%, but failed to significantly modify the increase in AVP levels (7.2 +/- 2.2 pg/ml), the latency time to emesis (149 +/- 2 min) and the number of emetic episodes induced by cisplatin. These results suggest that AII does not mediate cisplatin-induced emesis, nor does it mediate the increase in AVP observed at the time of emesis. We propose that AVP may be a good marker for nausea and emesis, and that increases in AVP may be neurally-mediated. The large increase in circulating AVP may represent a desirable water conservation response in anticipation of fluid losses induced by vomiting. PMID- 2314193 TI - Evidence for lipid peroxidation in atherosclerosis. AB - Lipid peroxidation may play a significant role in the initiation and progression of atherosclerotic plaque. Freshly harvested normal and atherosclerotic human aortic tissue, coronary arteries and explanted vein grafts were snap frozen at 70 degrees C. Folch reagent (chloroform-methanol 2:1, v/v) was used to extract lipids from the homogenates. These extracts were assayed for cholesterol, phospholipid and triglyceride content. Lipid peroxide complexes in vessels were measured fluorometrically. Atherosclerotic plaque from patients with aortic aneurysmal and occlusive disease and coronary artery disease contained significantly greater amounts of cholesterol (15.54 +/- 9.71 vs 3.39 +/- 1.14 mg/g tissue) than controls (p less than 0.01). Lipid peroxide fluorochromes were similarly elevated in all atherosclerotic tissue (4.159 +/- 1.065 vs 3.087 +/- 0.497 fluoro units/g tissue) compared to control (p less than 0.01) with significant elevations in saphenous vein grafts and occlusive aortic disease. Although lipid peroxidation and lipid accumulation occur in close association in atherosclerotic plaque, the role of lipid peroxides in the pathogenesis of atherosclerosis remains to be determined. PMID- 2314192 TI - Interrelationships between plasma homovanillic acid and indices of dopamine turnover in multiple brain areas during haloperidol and saline administration. AB - Haloperidol or saline was administered to rats daily for 1, 8, 15 or 22 days. During haloperidol, but not saline administration, changes in plasma homovanillic acid (HVA) concentrations were correlated with changes in nucleus accumbens HVA. Haloperidol administration also had a significant effect on the intercorrelation of dopamine (DA) concentrations and indices of DA turnover across multiple brain areas. In particular, intercorrelations of HVA concentrations among DA terminal brain areas (i.e. striatum, nucleus accumbens, and olfactory tubercle) occurred only during haloperidol treatment. PMID- 2314194 TI - Central mechanisms of action involved in cocaine-induced tachycardia. AB - The present study was designed to determine the central effects of cocaine on heart rate and blood pressure in Wistar Kyoto rats (WKY) and to evaluate mechanisms involved in the response. Cocaine (0.025-4 mg/kg) was administered to unanesthetized, unrestrained rats via a cannula placed into the lateral ventricle. Procaine (0.1 and 4 mg/kg) was also administered centrally. Cocaine did not significantly alter blood pressure at doses of 0.025, 0.1, or 0.5 mg/kg, icv. Only the highest dose, 4 mg/kg, icv produced a significant pressor response. Cocaine produced significant dose-dependent tachycardia, with the maximum increase in heart rate occurring within 5 min. Procaine (4 mg/kg, icv) produced tachycardia, but the effect was significantly less than that produced by cocaine (4 mg/kg, icv). Cocaine also produced tachycardia at a dose of 0.1 mg/kg, but procaine did not significantly alter heart rate at the same dose. Central phentolamine pretreatment (0.1 mg/kg, icv) significantly attenuated the increase in heart rate produced by cocaine. These results indicate that the centrally mediated tachycardia produced by cocaine is partly due to its local anesthetic activity and to indirect stimulation of alpha receptors. PMID- 2314195 TI - Early events of RNA polymerase II transcription initiation. AB - We have investigated the earliest stages of assembly of an RNA polymerase II transcription complex. General transcription factors from HeLa cells were partially purified and assayed using the adenovirus-2 major late promoter. Preincubation of either all the transcription factors (TF) with the DNA or only the subset consisting of TFIIA, TFIID, and DNA overcame the 15-20 min lag normally observed. The kinetics demonstrate that TFIIA first interacts with the template over a 5 min. period, and then TFIID interacts with the IIA:DNA complex over a 2 min. period. The remainder of the necessary transcription factors then interact with the IIA:IID:DNA complex. There are apparently interactions between IIA and IID, as a pre-incubation of these factors (without DNA) overcomes the lag period. Both IIA:DNA and IIA:DNA:IID interactions are temperature sensitive, resulting in slower kinetics at 0 degree C. Thus, the kinetics of transcription involve activation processes in addition to DNA binding. PMID- 2314196 TI - Effect of multiple dosing on the analgesic action of diflunisal in rats. AB - This investigation was designed to compare the analgesic effect of the initial dose of a repetitively dosed non-narcotic analgesic with the analgesic effect of a subsequent dose given 3 days later. To exclude gradual drug accumulation as a variable, the first ("loading") dose was larger than the maintenance doses. Male Sprague-Dawley rats received 100 mg/kg diflunisal i.v. as the first dose and 70 or 75 mg/kg every 12 hours thereafter. The analgesic effect of the first and seventh doses was determined as the pain threshold (voltage) upon electrical stimulation of the tail every 15 to 30 minutes from the third to the ninth hour after dosing. Blood samples for drug assay were obtained at 3 and 9 hours. A control group received injections of solvent for 6 doses and 100 mg/kg diflunisal as the seventh dose. There were no statistically significant differences between the area under the total or free (unbound) drug concentration versus time curves of the first and seventh dose but the average analgesic effect (area under the voltage increase versus time) of the seventh dose was only 28 percent that of the first dose. The areas under the drug concentration and analgesic effect versus time curves of the diflunisal dose given as the seventh injection to the control rats were similar to those produced by the first dose given to the multiple dosed rats. The results of this investigation show that the analgesic effect of a non narcotic drug decreases substantially during repeated dosing in an animal model of experimental pain. This change in pharmacologic response has the characteristics of functional rather than pharmacokinetic tolerance in that there was no change in the drug concentration profile with time and no effect of the manipulations as such (i.e., repeated pain threshold determinations and blood withdrawals) on diflunisal-induced analgesia. These observations may have important implications for the evaluation and use of non-narcotic analgesics in the management of clinical pain. PMID- 2314197 TI - [The differential diagnosis of thyroid cancer using radioimmunologic analysis]. AB - Clinical and radioimmunoassay investigations performed in 162 patients with different thyroid diseases, have shown that changes in the levels of T3, T4 and TSH do not allow assessment of the nature of a tumor process. The level of calcitonin is a tumor marker of medullary carcinoma and C-cell thyroid adenomas. In the absence of pathological changes in the thyroid an increase in the level of thyroglobulin can be regarded as a tumor marker of metastatic growth of papillary and papillary-follicular cancer. PMID- 2314198 TI - [Radioimmunologic research in the complex assessment of thyroid status in primary hypothyroidism]. AB - Radioimmunoassay data on the determination of the plasma levels of free and bound forms of thyroid hormones and TSH in various types of primary hypothyrosis were analyzed. The variability of analyzed indices was revealed; changes in the thyroid status according to the results of hormonal investigations were more noticeable in idiopathic hypothyrosis, the least noticeable in patients with hypothyrosis operated on for diffuse toxic goiter. Changes detected in patients with severe-type hypothyrosis did not depend on the type of disease. PMID- 2314199 TI - [Thermography with glucose loading in the examination of women at high risk of developing breast cancer]. AB - Thermography of the breast with pharmacological GTT was performed in 260 women; cancer was diagnosed in 150 of them, benign breast diseases in 110. A significant increase in temperature asymmetry after GTT was shown in breast cancer patients as compared to patients with benign diseases. Data on the sensitivity of the mammographic and thermographic methods to identify risk groups were presented. PMID- 2314200 TI - [The function of the hepatobiliary system in patients with cholelithiasis based on hepatocholescintigraphic data]. AB - Function of the hepatobiliary system in 35 patients with cholelithiasis of mild and average grave types and in 36 examinees after cholecystectomy without complaints and with the post-cholecystectomy syndrome was assessed with dynamic hepatocholescintigraphy which was shown to be an effective method for assessment of the hepatobiliary system in patients with cholelithiasis and after cholecystectomy. In some patients with cholelithiasis a degree of hepatobiliary disorders, including the frequency of dyskinetic disturbances, grows progressively with the severity of pathology (from a mild clinical type to an average grave one) and is most expressed in patients suffering from the postcholecystectomy syndrome. PMID- 2314201 TI - [The effect of potassium iodide on the pharmacokinetics of radioactive iodine labelled antibodies]. AB - Radioactive iodine-labeled rabbit antibodies to beta 1-MA antigen (the marker of human colon cancer) were injected iv to BALB/c mice as well as to nude mice with xenografts of various human tumors. Preparations of iodinated antibodies contained an admixture of protein-unbound radionuclide 2-4% of total radioactivity. Part of the recipient animals were given per os 0.1% solution of KI to block the thyroid from radioactive iodine. A comparative study was made of the distribution of radioactivity in the tissues of recipients in the time course of 7 days. The thyroid of nude mice with tumors was shown to uptake much more radioactivity than that of immunologically intact mice. In addition to its protective effect of the thyroid from radioactive iodine, KI also enhanced the excretion of the preparation of labeled antibodies. Possible mechanisms of the revealed phenomena were analyzed. PMID- 2314202 TI - [The direct use of cytogenetic data for plotting prognostic curves of the dynamics of neutrophil count after acute relatively uniform gamma irradiation (based on data from the victims of the accident at the Chernobyl Atomic Electric Power Station]. AB - A considerable number of irradiated persons appeared as a result of the accident at the Chernobyl Atomic Power Station. Analysis of chromosome aberrations and detailed hematological investigations were performed in them. Relatively uniform affection of the hemopoietic tissue could be anticipated on the basis of the results of the cytogenetic analysis in most of these persons who had been exposed to radiation at doses that were critical for the development of the bone marrow syndrome. It made it possible to establish direct quantitative relationship between the indices of a postradiation curve of the time course of the neutrophil count in peripheral blood and the mean rate of dicentrics in lymphocytes for cases of relatively uniform irradiation and to plot prognostic curves of neutrophils for different frequencies of dicentrics. PMID- 2314203 TI - [Theoretical simulation of temperature distribution in electromagnetic hyperthermia of tumors]. AB - Combined methods of tumor therapy including electromagnetic hyperthermia are used nowadays in many countries of the world. Ordinary control of temperature at several points of a heated volume by invasive temperature sensitive elements gives approximate evaluation of a temperature profile during a session of hyperthermia. The authors have proposed methods for the calculation of temperature distributions in tissues taking account of the correlation of the blood flow and temperature and its contribution to heat transfer processes in body tissues. It is assumed that the vessels are equally distributed in the body volume sparing a necessity to record each one individually. The rated temperature profiles by the depth of a heated body zone corresponding to different variants of a UHF radiator and a tumor are given. Some conclusions as to the peculiarities of electromagnetic heating of body tissues have been drawn. PMID- 2314204 TI - [The RX-PLAN--a computer system for planning radiation treatment]. AB - The authors presented a system of radiation treatment design (RT)--RX-PLAN developed at the N. N. Burdenko Main Military Hospital in 1988 on the basis of a PC of DVK-3M type. The use of the PC with a graphic interface made it possible to meet the following specific requirements: input, imaging, processing and output of graphic data and to make an automated working place of low cost for radiologists (a physicist and a physician). PMID- 2314205 TI - [Dosimetric characteristics of the C-4 grid diaphragm from a kit of shaping fittings]. AB - A kit of equipment is manufactured at present for gamma-beam therapeutic units. The authors describe the design and geometrical parameters of a new grid diaphragm C-4 included in this kit. Characteristics of a dose field, formed by this grid, have been studied and are presented in this paper. Particular attention during the calculation of the dose time of an irradiation session under the opening should be drawn to an error in beam alignment. PMID- 2314206 TI - [The shape of the absorbed dosage in neutron irradiation of a water phantom]. AB - The paper is concerned with the results of experimental and estimated investigations into the spatial distribution of an absorbed dose and the spectrum of neutrons during irradiation of a water phantom by a P-3 beam of a BP-10 reactor. The ratio of densely ionizing and rarely ionizing components of an absorbed dose as well as the ratios between neutrons of different energetic groups were shown to undergo considerable changes with the penetration of reactor neutrons into the depth of a tissue-equivalent medium. The obtained results serve as basic data in various biomedical investigations using reactor neutron beams, including the planning of their use in cancer therapy. PMID- 2314207 TI - [Beta therapy of vulvar leukoplakia]. PMID- 2314208 TI - [Deontologic problems of clinical radiology]. PMID- 2314209 TI - [Determination of the separate clearance of the kidneys using radionuclide methods]. PMID- 2314210 TI - [The effect of local UHF hyperthermia and a fractionated radiation dosage on the incidence of perichondritis during the treatment of laryngeal cancer]. AB - Perichondritis in patients treated by a continuous course were noted in 12.5 +/- 1.5%, in patients treated by a split method--in 4.6 +/- 1.2%, in chemoradiotherapy--in 5.75 +/- 1.3%, in thermoradiotherapy--in 3.0 +/- 2.9%, and after synchronization using 5-FU and large fractions--in 30.5 +/- 3.9%. Complications appeared mainly during the 1st year (85%), after 2-3 yrs.--in 8.4%, later on--in 6.6%. Local hyperthermia did not cause an increase in the number of complications. PMID- 2314212 TI - Discriminant factor analysis of 31P NMR spectroscopic data in myopathies. AB - Discriminant factor analysis (DFA) enables one to distinguish among diagnostic groups using diagnostic variables. It provides discriminant functions that are linear combinations of the diagnostic variables and that optimally separate diagnostic groups. It was used to enhance the accuracy of 31P NMR data in the diagnosis of myopathies. DFA allowed a good separation of normal subjects, congenital neuromuscular disorders with type I fiber predominance, and McArdle's diseases. It elicited an unexpected homogeneity of idiopathic rhabdomyolyses, the metabolic origin of which is unknown, and suggested that the abnormality could involve the mitochondrial oxidative metabolism in some of them. In mitochondrial myopathies, an expected heterogeneity is shown by DFA. It may allow an automatic diagnosis of some myopathies from 31P NMR data or guide biochemists by comparing biochemical features of a new patient to those of previously established groups. PMID- 2314211 TI - Epicardial and endocardial localized 31P magnetic resonance spectroscopy: evidence for metabolic heterogeneity during regional ischemia. AB - Previous studies have noted that myocardial blood flow and high energy phosphates are heterogeneous across the myocardial wall during ischemia. In order to determine whether differences in metabolites between the subendocardium and subepicardium could be detected using 31P magnetic resonance spectroscopy, the Fourier series window (FSW) experiment was implemented on a porcine model of graded regional ischemia. FSW experiments using a planar phantom showed a 46% improvement in localization to the subendocardium compared to a one-pulse experiment. Animal studies of graded ischemia demonstrated a gradient in the phosphocreatine to inorganic phosphate ratio in the myocardium that paralleled the gradient in blood flow. These studies demonstrate the ability of spatially localized 31P magnetic resonance spectroscopy to detect regional changes in myocardial high energy phosphates localized to the subepicardium and subendocardium. PMID- 2314213 TI - Comparison of 31P MRS and 1H MRI at 1.5 and 2.0 T. AB - The goals of this study were to compare 31P magnetic resonance spectroscopy (MRS) and 1H magnetic resonance imaging (MRI) of human subjects and phantoms at 1.5 and 2.0 T. The 31P signal-to-noise (S/N) ratios in phantom standards and in localized volumes in human brain and liver were compared at 1.5 and 2.0 T. In addition, T1 values for 31P resonances in human brain, 31P linewidths of metabolites in human brain and liver, 1H S/N in a phantom standard, and MR image quality in human head and body were compared at the two field strengths. The results of our study showed that at the higher strength field, (1) in vivo 31P MRS studies benefited from up to 32% improvement in S/N; (2) in vivo 31P MRS studies also benefited from increased spectral dispersion; (3) the quality of MR head images remained comparable; and (4) body images showed some decrease in image quality due to increased chemical shift, and flow and motion artifacts. PMID- 2314214 TI - Spatial localization for motion-rejected NMR imaging: SLO-MOTION. AB - A new method of eliminating NMR image artifacts caused by random or sporadic motion is presented. The method uses only NMR techniques. A combination of a spatial localization method and a standard 2DFT imaging sequence is employed and consequently named SLO-MOTION. Alternatively, the sequence may be used to aid motion artifact reduction by postprocessing methods. The feasibility of the method is demonstrated on a phantom. PMID- 2314215 TI - The crossover surface coil: an efficient in vivo NMR detector. AB - The crossover surface coil is constructed with two turns of copper foil using a unique transposition construction which incorporates an explicit center tap ground of the widened bottom layer. The coil reduces dielectric and inductive losses by effective shielding of electric fields and uniform distribution of magnetic fields for minimum Q losses upon loading of the coil. Flexible, copper foil construction permits easy conformation to tissues of interest, enhancing coil performance. Construction details of the crossover coil and Q data for coils of various sizes operating at a number of frequencies are given. PMID- 2314216 TI - Numerical analysis of multislice MR excitation and inversion with multifrequency selective rf pulses. AB - Multifrequency selective excitation and inversion were recently described and tested for multislice imaging and multivolume selective spectroscopy (Magn. Reson. Med. 6, 364 (1988), J. Magn. Reson. 76, 155 (1988]. The technique is based on assumption that a multifrequency rf pulse, a linear superposition of several selective rf pulses with different frequencies, generates a MR signal which can be separated into the spin responses due to each individual frequency. This assumption is investigated theoretically by analyzing the effect of multifrequency selective rf pulses on the magnetization of a homogeneous phantom as a function of slice separation, pulse shape, and rf amplitude using computer simulations of the Bloch equations. It is found that multifrequency selective excitation with sinc pulses--up to eight slices are investigated--and two frequency inversion with hyperbolic secant pulses lead to profiles comparable in quality and selectivity to those of conventional single-frequency pulses. PMID- 2314217 TI - A study of optimization of the complex hyperbolic secant inversion pulses. AB - The conjugate gradient method is used to optimize the inversion slice profile produced by complex hyperbolic secant selective pulses. An improved quality is obtained for the inversion slice profile at a price, however, of a lower immunity to the amplitude variation of radiofrequency pulses. PMID- 2314218 TI - Environmental optimization and shielding for NMR experiments and imaging in the earth's magnetic field. AB - For many years, a number of laboratories have been working on the applications of very low field NMR. In 1985, our laboratory presented the first NMR images using the earth's magnetic field. However, the use of this technique was limited by the weakness of the signal and the disturbing effects of the environment on the signal-to-noise ratio and on the homogeneity of the static magnetic field. Therefore experiments has to be performed in places with low environmental disturbances, such as open country or large parks. In 1986, we installed a new station in Lyon, in the town's hostile environment. Good NMR signals can now be obtained (with a signal-to-noise ratio better than 200 and a time constant T2 better than 3s for 200-mnl water samples and at a temperature of about 40 degrees C). We report the terrace roof of our faculty building. Gradient coils were used to correct the local inhomogeneities of the earth's magnetic field. We show FIDs and MR images of water-filled tubes made with or without these improvements. PMID- 2314219 TI - Triple-quantum-coherence-filtered imaging of sodium ions in vivo at 4.7 tesla. AB - The tissue distribution of sodium ions which generate triple-quantum coherence (TQC) in vivo is determined from images. A technique for filtering conventional sodium images, so that signal is obtained only from sodium ions which have a correlation time appropriate for producing TQC, is described. The utility of TQC filtered sodium images is demonstrated in a study of tumors implanted in a nude rat model, where the intensity of the TQC signal from sodium ions in the growing margin of the tumor is observed to be 200-250% greater than that from surrounding tissue. PMID- 2314220 TI - Echo-planar imaging of the human fetus in utero. AB - We have demonstrated that echo-planar imaging can be used to produce high-quality snapshot images of the human fetus in utero in a fraction of a second. These images are free of motional artifact or blurring and allow detailed depiction of fetal structures in normal and pathological pregnancies. PMID- 2314222 TI - Parameter estimation for in vivo magnetic resonance spectroscopy (MRS) using simulated annealing. AB - A method for estimating the spectral parameters from a noisy FID is proposed. The method uses a priori information concerning the lower and upper limits between which such parameters' values can exist. Computer simulation results show that, using the proposed method, values of the spectral parameters can be accurately estimated from a noisy FID. PMID- 2314221 TI - Uterine cervical punch biopsy specimens can be analyzed by 1H MRS. AB - Biopsy specimens of the uterine cervix, including colposcopically directed punch biopsy specimens of females with atypical Papanicolaou smear tests, are suitable for analysis by magnetic resonance (MR) spectroscopy. A narrow lined lipid MR spectrum, characteristic of malignant tissue, is obtained from a 6-mm3 biopsy specimen of histologically confirmed squamous carcinoma of the cervix. In contrast, specimens containing inflammatory cells generate a broad component only centered at 1.3 ppm with a T2 relaxation value of less than 350 ms. Most biopsy specimens which contain dysplastic cells or evidence of human papilloma virus (HPV) infection have a discernible lipid spectrum similar to that of the malignant tissue specimen. Long T2 relaxation values found in malignant tissue specimens at 1.3 and 1.2 ppm are observed in some but not all of the biopsies which show evidence of HPV infection. The suitability of small tissue samples, such as punch biopsy specimens, for study by MR illustrates the sensitivity of this technique and its potential as an aid to histopathological discrimination between the various precursor states of cervical cancer. PMID- 2314223 TI - Selective access in cued recall: the roles of retrieval cues and domains of encoding. AB - The purpose of these experiments was to determine whether retrieval access in cued recall can be selectively restricted to a single domain of encoding when information has been encoded within two domains as different as word sound and word meaning. In Experiment 1, the subjects studied pairs of rhyming words differing in rhyme set size under verbal-repetition or interactive-imagery instructions. Recall was cued with study-context rhymes, with extralist rhymes, or with extralist associates. The results indicated that rhyme set size and instructional effects were found no matter how recall was cued, indicating that both domains of encoding were always accessed. In Experiment 2, potential effects of study time and overt naming of the test cues were explored. These results indicated that both domains of encoding were accessed, except when long study times were available and subjects did not have to name the rhyme test cues. Rhyme set-size effects were eliminated under these conditions, suggesting that selective access to encoded meaning is possible in cued recall. Retrieval access in this task appears to be more controlled by domains of encoding than by information directly available in the cue, and access to encoded information can be restricted to a single domain. PMID- 2314224 TI - Recollective experience in word and nonword recognition. AB - The functional relationship between memory and consciousness was investigated in two experiments in which subjects indicated when recognizing an item whether they could consciously recollect its prior occurrence in the study list or recognized it on some other basis, in the absence of conscious recollection. Low-frequency words, relative to high-frequency words, enhanced recognition accompanied by conscious recollection but did not influence recognition in the absence of conscious recollection. By contrast, nonwords compared with words enhanced recognition in the absence of conscious recollection and reduced recognition accompanied by conscious recollection. A third experiment showed that confidence judgments in recognizing nonword targets corresponded with recognition performance, not with recollective experience. These measures of conscious awareness therefore tap qualitatively different components of memory, not some unitary dimension such as "trace strength." The findings are interpreted as providing further support for the distinction between episodic memory and other memory systems, and also as providing more qualified support for theories that assume that recognition memory entails two components, one of which may also give rise to priming effects in implicit memory. PMID- 2314225 TI - On time differences in searching for letters in words and nonwords: do they emerge during the initial encoding or the subsequent scan? AB - Krueger (1970a, 1970b, 1982) has demonstrated that subjects can search for target letters within words faster than they can complete an equivalent search through nonwords, and he further demonstrated that the effect did not arise during the comparison stage. The present study involved three experiments in which the usual word advantage disappeared either when subjects knew where within a display the target item would appear (i.e., it was always the first letter), or when all the component letters were encoded into memory before the task began (i.e., a memory search task). These data, in conjunction with Krueger's, where interpreted as localizing at least one (and possibly the only) source of the word-nonword difference in this task to the events that occur during the item-to-item transitions subjects make when scanning the letter arrays. That is, these transitions are faster for words than nonwords, and it was suggested that the time difference may emerge because although all the letters from within a word appear to be available in memory before the scan begins, this seems not to be true for consonant arrays. Given that this is the case, part of the word-nonword difference may be attributable to subsequent encoding events that would be needed for the consonant arrays as the scan moves from letter to letter. PMID- 2314226 TI - An odd effect: lengthened reaction times for judgments about odd digits. AB - Eight experiments are reported that first establish and then explicate a serendipitous finding that judgments about whether digits are odd or even take longer for odd than for even digits. The slowing of judgments about odd digits is more pronounced when digit pairs or triples are used, but is still weakly present when a single digit must be classified. A similar effect is seen when judgments of nouns are based on whether the nouns are the names of living or dead objects. Nouns that name dead objects are judged more slowly than ones that name living objects. The concept "alive" is linguistically marked. Past research has shown that unmarked concepts are processed more rapidly than marked ones. The similarity in the pattern of results when digits and words are judged is used to argue that the slower judgments about odd digits are due to the fact that "odd" is a linguistically marked and "even" a linguistically unmarked concept. PMID- 2314228 TI - Memory for script actions: effects of relevance and detail expectancy. AB - Script actions that varied both in relevance to the script and in the expectancy of their details were developed. In Experiment 1, recall of these actions was tested. Actions of medium relevance were recalled better than actions of high or low relevance, whether or not details were presented. However, the unexpected details themselves were recalled better than the expected details. In Experiment 2, recognition was lowest for high-relevance actions but medium- and low relevance actions did not differ. Actions with unexpected details were recognized better than actions with expected details, which tended to be better than generic actions. The results were interpreted as showing that both the relevance and the expectancy of the details in script actions are important in memory, but that the two dimensions may play different roles. PMID- 2314227 TI - The conjunction fallacy? AB - Tversky and Kahneman (1983) showed that when subjects are asked to rate the likelihood of several alternatives, including single and joint events, they often make a "conjunction fallacy." That is, they rate the conjunction of two events as being more likely than one of the constituent events. This, they claim, is a fallacy, since the conjunction of two events can never be more probable than either of the component events. In addition, they found that prior training in probability theory does not decrease the likelihood of making this fallacy. We argue that in some contexts, an alternative that contains the conjunction of two events can be more probable than an alternative that contains only one of the conjunction's constituent events. We carried out four experiments in which we manipulated this context. The frequency of making a conjunction fallacy was affected by the manipulation of context. Furthermore, when the context was clearly specified, prior training in statistics influenced the ratings. PMID- 2314229 TI - Knowledge acquisition and strategic action in "Mastermind" problems. AB - In two experiments, the strategies used by subjects playing the logical-deduction game, Mastermind, were examined. In the first experiment, subjects showed improvement resulting from the continued use of a particular strategic action, and the data suggested that the subjects learned the strategy from their transactions with the task. In the second experiment, the question of changes in underlying strategic knowledge of Mastermind was examined. The accuracy and complexity of the subjects' deductions and their use of the previously identified strategy were used to generate a model of the cognitive operations involved in Mastermind. Although there were improvements in the accuracy and complexity of the subjects' deductions resulting from continued play, these improvements were unrelated to the use of the strategy. Moreover, the likelihood of making accurate and complex deductions was well accounted for by a Markovian model, suggesting that the deployment of the strategy was not driven by any change in the subject's underlying knowledge structures. Rather, the subjects seemed to use the strategy to create Mastermind situations whose interpretation was fairly easy. The implications for previous work on the issue of Mastermind strategies and the development of logical-deduction strategies are discussed. PMID- 2314230 TI - An on-line assessment of causal reasoning during comprehension. AB - Fletcher and Bloom (1988) have argued that as readers read narratives, clause by clause, they repeatedly focus their attention on the last preceding clause that contains antecedents but no consequences in the text. This strategy allows them to discover a causal path linking the text's opening to its final outcome while minimizing the number of times long-term memory must be searched for missing antecedents or consequences. In order to test this hypothesis, we examined the reading times of 25 subjects for each clause of eight simple narrative texts. The results show that: (1) causal links between clauses that co-occur in short-term memory (as predicted by the strategy) increase the time required to read the second clause; (2) potential causal links between clauses that never co-occur in short-term memory (again as predicted by the strategy) have no effect on reading time; and (3) reinstatement searches are initiated at the end of sentences that are causally unrelated to the contents of short-term memory or that contain clauses that satisfy goals no longer in short-term memory. These results support the claim that subjects engage in a form of causal reasoning when they read simple narrative texts. PMID- 2314231 TI - Effects of repetition of mental operations on memory for occurrence and origin. AB - In two experiments, subjects read or generated items at both encoding and retrieval. At test, they were required to decide whether or not the targets were presented initially (recognition), and if so, whether they were initially read or generated (judgments of origin). Recognition for items that were initially generated was enhanced if they were once again generated at test in the same context, but not if they were generated at test without context. These results confirm that memory for occurrence is facilitated by repetition of the initial encoding operations at retrieval. Generating at test resulted in an increase in "generate" responses both for items that were initially generated and for items that were initially read. Overall, there was a decrease in the accuracy of origin discriminations. It is suggested that, when subjects generate at test, they are likely to mistakenly attribute these just-performed operations to be part of the memory trace for that item. PMID- 2314232 TI - Selecting analogous problems: similarity versus inclusiveness. AB - Students were asked to select one of two analogous problems in order to solve algebra word problems. In Experiment 1, one problem was less inclusive and the other was more inclusive than a test problem. The students judged the complexity and similarity of problems, selected analogous problems, and used the solutions to solve test problems. They performed significantly better on the test problems when given the more inclusive solutions, but used perceived similarity rather than inclusiveness to select analogous problems. The same pattern of results occurred in Experiment 2, in which isomorphic problems replaced the more inclusive problems. The results show that students are deficient in selecting good analogies, both from the same category (Experiment 1) and from a different category (Experiment 2). Students who saw the analogous solutions (Experiment 3) or were majoring in mathematics (Experiment 4) were more likely to select an isomorphic problem over a less inclusive problem, but were not more likely to select a more inclusive over a less inclusive problem. PMID- 2314233 TI - The spatial frame of reference in object naming and discrimination of left-right reflections. AB - The effects of stimulus rotation and observer's head-tilt position on various pattern-recognition tasks were investigated to compare the external directions most closely aligned with the spatial frame of reference. Specifically, the effects of these factors on the time to name objects were compared with their effects on the time to discriminate left-facing from right-facing lateral views of these objects, as well as with their effects on the time to discriminate normal from mirror-imaged alphanumeric characters. The naming task relied upon a reference frame more closely aligned with retinal directions than with environmental directions. In contrast, both discrimination tasks relied upon a frame aligned more closely with environmental directions. Overall, the nature of the task exerts a greater influence on the directions with which the frame of reference is aligned than do the stimulus attributes. PMID- 2314234 TI - Guide to protein purification. PMID- 2314235 TI - Preparation of extracts from plants. PMID- 2314236 TI - Setting up a laboratory. PMID- 2314237 TI - Preparation of extracts from higher eukaryotes. PMID- 2314239 TI - Detergents: an overview. PMID- 2314238 TI - Preparation of membrane fractions. PMID- 2314240 TI - Buffers: principles and practice. PMID- 2314241 TI - Removal of detergents from membrane proteins. PMID- 2314242 TI - Precipitation techniques. PMID- 2314243 TI - Precipitation of proteins with polyethylene glycol. AB - Polyethylene glycol is a nondenaturing water-soluble polymer whose ability to precipitate protein from aqueous solution can be qualitatively understood in terms of an excluded volume mechanism. The increment in PEG concentration required to effect a given reduction in solubility is unique for a given protein polymer pair, being insensitive to solution conditions and primarily dependent on the size of the protein and polymer. Selective manipulation of the solubility of specific proteins through control of their state of association or ligand environment can potentially remove some of the empiricism otherwise involved in fractional precipitation. Adequate methods for removing the polymer are available. PMID- 2314244 TI - Ion-exchange chromatography. PMID- 2314245 TI - Gel filtration. PMID- 2314246 TI - Hydrophobic chromatography. PMID- 2314247 TI - Chromatography on immobilized reactive dyes. PMID- 2314248 TI - Affinity chromatography: general methods. PMID- 2314249 TI - Measurement of enzyme activity. PMID- 2314250 TI - Chromatofocusing. PMID- 2314251 TI - High-performance liquid chromatography: effective protein purification by various chromatographic modes. PMID- 2314252 TI - One-dimensional gel electrophoresis. PMID- 2314253 TI - Protein analysis using high-resolution two-dimensional polyacrylamide gel electrophoresis. PMID- 2314254 TI - Isoelectric focusing. PMID- 2314255 TI - Elution of protein from gels. PMID- 2314256 TI - Quantitation of protein. PMID- 2314257 TI - Determination of purity. PMID- 2314258 TI - Determination of size, molecular weight, and presence of subunits. PMID- 2314259 TI - Amino acid analysis. PMID- 2314260 TI - Protein crystallization. PMID- 2314261 TI - Preparation of polyclonal antibodies. PMID- 2314262 TI - Preparation of monoclonal antibodies. PMID- 2314263 TI - Protein blotting and immunodetection. PMID- 2314264 TI - Concentration of proteins and removal of solutes. PMID- 2314265 TI - Using purified protein to clone its gene. PMID- 2314266 TI - Computer analysis of protein structure. PMID- 2314267 TI - Rethinking your purification procedure. PMID- 2314268 TI - Purification and crystallization of transaldolase from Candida utilis. PMID- 2314269 TI - Maintaining protein stability. PMID- 2314270 TI - Molecular evolution: computer analysis of protein and nucleic acid sequences. PMID- 2314271 TI - Finding protein similarities with nucleotide sequence databases. AB - In this chapter we describe strategies for the searching of translated nucleotide sequence databases. By applying standard searching techniques developed for protein databases, we have found that previously unrecognized homologies can be detected. In addition, we have shown that extremely high sensitivity can be obtained using the scoring matrix strategy for short regions of similarity. The latter approach is particularly effective for detecting homologs found at the ends of sequences and within data of poor quality. These individual methods are demonstrated for the LysR family of bacterial activator proteins. Successive applications of these methods allow for sensitive detection of complex relationships, as demonstrated for the AraC family and for the complex LuxR-OmpR NtrC families of bacterial activator proteins. Although our examples are drawn from bacterial sequences, these methods are likewise effective for higher eukaryotic genomic sequences, where protein-coding sequences are usually interrupted by introns. This should be particularly important in the future, since much of the expected increase in nucleotide sequence databases is likely to come from eukaryotic genomic sequencing projects. PMID- 2314272 TI - Use of homology domains in sequence similarity detection. AB - We have found the detection of homology domains using a nonlinear similarity score and the DD algorithm to be a useful approach for identifying similarity between sequences and evaluating potential homology. There are several reasons for the success of the method. (i) Homology domains are identified by a rigorous method that guarantees they will be locally optimal. (ii) The relative significance of different homology domains can be directly compared using the nonlinear similarity score. (iii) Different cost matrices can be used in the calculation of the similarity score. (iv) Relatively long sequences can be compared in a single pass as storage requirements are proportional to the shorter of the two sequences being compared. (v) The method has proved to be very sensitive in practice. (vi) The boundaries of authentic regions of homology are accurately identified. (vii) The information required to define a homology domain (its location, size, similarity score, etc.) can be stored in a compact data structure, facilitating the sharing of homology domain data among different software tools. (viii) The method can be applied to similarity searches of the nucleotide and protein sequence data banks. These properties make the identification of homology domains for studying sequence similarity a useful companion to other accepted methods, such as dynamic programming based analyses. PMID- 2314273 TI - Profile analysis. PMID- 2314274 TI - Finding protein coding regions in genomic sequences. PMID- 2314275 TI - Ancient patterns in nucleic acid sequences. PMID- 2314276 TI - Consensus methods for DNA and protein sequence alignment. PMID- 2314277 TI - EMBL Data Library. PMID- 2314278 TI - Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project. PMID- 2314279 TI - GenBank: current status and future directions. PMID- 2314280 TI - Protein sequence database. PMID- 2314281 TI - Mutation data matrix and its uses. PMID- 2314282 TI - Sensitivity comparison of protein amino acid sequences. PMID- 2314284 TI - Protein multiple sequence alignment and flexible pattern matching. PMID- 2314285 TI - Genomic divergence through gene rearrangement. PMID- 2314283 TI - Progressive alignment and phylogenetic tree construction of protein sequences. PMID- 2314286 TI - Multiple sequence comparison. PMID- 2314287 TI - Simultaneous comparison of several sequences. PMID- 2314288 TI - Significance of protein sequence similarities. PMID- 2314289 TI - Fast alignment of DNA and protein sequences. PMID- 2314290 TI - Cooperation between databases and scientific community. PMID- 2314291 TI - Statistical methods for estimating sequence divergence. PMID- 2314292 TI - Converting distance to time: application to human evolution. PMID- 2314293 TI - Maximum likelihood methods. PMID- 2314294 TI - Maximum parsimony approach to construction of evolutionary trees from aligned homologous sequences. PMID- 2314295 TI - Phylogeny determination using dynamically weighted parsimony method. PMID- 2314296 TI - Unified approach to alignment and phylogenies. PMID- 2314297 TI - Statistical tests of molecular phylogenies. PMID- 2314298 TI - Nearest neighbor procedure for relating progressively aligned amino acid sequences. PMID- 2314299 TI - Searching through sequence databases. PMID- 2314300 TI - Multiplication in human blood and deoxyribonuclease production by group G streptococci isolated from animals and humans. AB - An M protein or an M protein-like substance was found to be present in a large proportion of group G streptococci isolated from animals and humans. Forty-seven percent of the isolates from cat throats and 38% of the isolates from the vagina of cats were able to multiply in human blood. Only 14% of the human isolates of group G isolated from various anatomical sites and sources were able to multiply in fresh human blood. Deoxyribonuclease was produced by 81% of cat vagina isolates, by 80% of cat throat isolates and by only 27% of the group G isolates from humans. Thirty-five percent of the cat isolates but only 5% of the human isolates were able to both grow in blood and produce DNase. PMID- 2314301 TI - Isolation of acid producing sorbitol-adapted bacteria from dental plaque using selective agar media. AB - Acidogenic bacteria metabolizing sorbitol were isolated and identified from dental plaque of twenty nine volunteers, claiming to be users (sixteen) and non users (thirteen) of sorbitol-containing chewing gum and candy. Sixty bacterial strains were isolated, using improved selective agar media. The taxonomy of twenty strains, all Gram-positive cocci, was determined employing a customized BBL MinitekR system and other biochemical reactions. The majority of these strains represented Streptococcus sanguis and Streptococcus acidominimus. Although sorbitol-metabolizing bacteria were found in plaque specimens of most persons tested, a larger number of acidogenic sorbitol degrading bacteria was detected in the plaque of the volunteer group claiming to use sorbitol-containing sweets. Bacteriological results indicate that frequent consumption of sorbitol containing products will lead to a shift in oral ecology, numerically favouring sorbitol-metabolizing bacteria. These sorbitol adapted bacteria appear to be as acidogenic as Streptococcus mutans in the presence of ordinary sugars. PMID- 2314302 TI - Fluid-phase endocytosis by primary cultures of bovine brain microvessel endothelial cell monolayers. AB - Blood-brain barrier (BBB) fluid-phase endocytosis was examined in primary cultures of bovine brain microvessel endothelial cell (BMEC) monolayers. By fluorescence spectroscopy. Lucifer yellow (LY, a fluorescent, soluble molecule used as a marker for pinocytosis) accumulation by BMEC was observed to be linear over a concentration range of 0.05 to 1.0 mg/ml. Time-dependent uptake of LY exhibited curvilinear kinetics composed of an initially rapid uptake rate of 1338 ng of LY/mg protein per hour at 0.5 mg/ml LY. Within 20 min, the rate of LY accumulation slowed to a steady-state rate of 23 ng of LY/mg protein per hour. Accumulation of LY was inhibited in the presence of metabolic inhibitors, potassium cyanide or 2-deoxyglucose, and was decreased, but not completely inhibited, at 4 degrees. Pulse-chase experiments revealed that efflux of LY was very rapid with at least 80% of the accumulated LY being lost within 2 min and was not sensitive to low temperature. Only 3-5% of the LY initially accumulated by BMEC remained cell-associated after a 30-min chase. The calculated turnover of the endocytic compartment's total volume (per hour) is 8- to 20-fold less than values for fibroblasts and macrophages, respectively. We have interpreted these data to suggest that the efflux of most of the LY involves loss from a rapidly recycled compartment of finite volume, possibly caveolae, that had sequestered marker during accumulation and suggest that these results are consistent with the present understanding of BBB pinocytosis in vivo. PMID- 2314303 TI - A new stimulation of the interaction between neutrophils and pulmonary endothelial cells. AB - To study the interaction between isolated homologous neutrophils and pulmonary endothelial cells under simulated in vivo conditions, we developed a model of the circulation in which neutrophils flow past endothelial cells. Endothelial cells from porcine pulmonary artery were grown on microcarriers, loaded into an elutriator chamber, and suspended (speed--300 rpm. flow--18 ml/min). Porcine neutrophils were labeled with 111In, mixed with a tracer dose of 125I-albumin, and injected into the elutriator inlet. Fractions were collected from the elutriator outlet and indicator dilution curves were plotted. Adherence of neutrophils was calculated by 1 - (area under 111In curve/area under 125I curve). In separate injections, neutrophils were preactivated with phorbol 12-myristate 13-acetate (100 ng/ml) or zymosan-activated plasma (10%, v/v). In three of eight lines of endothelial cells the adherence of activated neutrophils to cell-coated microcarriers was greater than that of nonactivated neutrophils. There was no difference in adherence to uncoated microcarriers or to the empty elutriator chamber between activated and nonactivated neutrophils. We conclude that this model will be useful for studying interactions between isolated neutrophils and endothelial cells because it incorporates flow in a physiologic milieu. PMID- 2314304 TI - An intact cremaster muscle preparation for studying the microcirculation by in vivo microscopy. PMID- 2314305 TI - The retinal microvasculature of spontaneously diabetic BB rats: structure and luminal surface properties. AB - Endothelial cell permeability and luminal surface anionic sites were studied in the retinal microvasculature of spontaneously diabetic rats. Horseradish peroxidase (HRP) was used as a tracer of pinocytotic transport, and cationized ferritin (CF) was used as a marker of luminal surface anionic sites. Diabetic and control rats were injected with HRP, and their retinas were fixed. Retinal tissue sections were then incubated in CF, reacted to visualize HRP, and prepared for quantitative electron microscopic analysis. In both control and diabetic rats treated with serotonin and histamine antagonists to prevent HRP-induced vascular changes, the endothelium formed a barrier to the tracer. Pinocytotic uptake was relatively low in most vessels. Reaction product was restricted to pinocytotic vesicles, tubular cisternae, and multivesticular bodies. HRP uptake appeared high in some of the deep capillaries of the diabetic retinas as compared with that of the controls, but the difference was not statistically significant. HRP-induced transendothelial permeability was observed in both control and diabetic rats when serotonin and histamine antagonist pretreatment was omitted. CF studies showed anionic sites in four luminal surface microdomains in control and diabetic endothelial cells. CF-binding, anionic sites were present on the plasma membrane, on all coated vesicles, on some uncoated vesicles, and on most diaphragms of uncoated vesicles. Plasma membrane binding was sparse and patchy in some diabetic vessels, especially in the deep vessels of rats that were not treated with the serotonin and histamine antagonists. However, statistical analysis showed similar numbers of plasma membrane binding sites in diabetic and control rats pretreated with serotonin and histamine antagonists. Our data suggest that the retinal microvasculature in diabetic rats remains normal in terms of permeability and luminal membrane anionic charge. PMID- 2314306 TI - Kinetic analysis of blood-brain barrier transport of D-glucose in man: quantitative evaluation in the presence of tracer backflux and capillary heterogeneity. AB - The present study deals with the analysis of double-indicator curves for blood brain barrier studies. Two mathematical models which provide for the estimation of backflux of tracer from brain to blood in conjunction with heterogeneity of the cerebral capillary and large-vessel transit times were used for the analysis of D-glucose transport on the basis of cerebral venous outflow curves. The two models, non-mixed and well mixed, arise from differing assumptions regarding the effective region surrounding the capillary lumen. An approximate solution for the well-mixed model was developed to increase computation speed. Fourteen D-glucose outflow curves and their reference curves were obtained from nine patients and subsequently analyzed by the two models. Further, in five patients data were obtained under different physiological conditions: normal, decreased, and increased cerebral blood flow rates. The results support the appropriateness of the well-mixed model and heterogeneity of the cerebral capillary transit times. The median value for the average extraction was 0.18 and the median distribution space was 0.14. The latter value is similar to the brain extracellular space that has been estimated by other methods. The extraction values calculated from the peak of the venous outflow curves were significantly smaller than the whole-brain average extraction values estimated with the well-mixed model (0.157 vs 0.178, P less than 0.0005). In summary: (a) capillary heterogeneity is present in the human brain and changes with cerebral blood flow; (b) after crossing the blood brain barrier, D-glucose distributes in the brain extracellular fluid; and (c) the extraction curve is significantly influenced by backflux. PMID- 2314307 TI - Associations between pericytes and capillary endothelium in the eel rete mirabile. AB - Morphometric analysis of electron micrographs of the eel rete mirabile revealed that pericytes occupied nearly one-third of the cellular volume of this organ with over 75% of the pericyte volume associated with arterially derived capillaries. These pericytes were highly arborized, extending processes which encircled the capillaries and covering, on average, more than 85% the ablumenal surface of arterially derived capillaries. Pericytes and endothelial cells interacted in a manner suggesting that pericyte activity modulates both capillary blood flow and permeability. PMID- 2314308 TI - Convection and diffusion measurements using fluorescence recovery after photobleaching and video image analysis: in vitro calibration and assessment. PMID- 2314309 TI - "The battered image syndrome"--we can overcome it. PMID- 2314310 TI - Infant feeding in adversity. "Why wrong for so long?". PMID- 2314311 TI - "Successful breastfeeding". PMID- 2314312 TI - A vision of the '90s? PMID- 2314313 TI - 1989 RCM professional day papers: infant feeding in adversity. Young mothers. PMID- 2314314 TI - A model for midwives--support for ethnic breast-feeding mothers. PMID- 2314315 TI - Health promotion with homeless families--extending the role of the midwife. PMID- 2314316 TI - Dame Juliet Rhys Williams Memorial Lecture 1989. Safe motherhood. PMID- 2314317 TI - Beware sheep! PMID- 2314318 TI - Diploma in professional studies in midwifery/advanced diploma in midwifery by distance learning. PMID- 2314319 TI - Water & birth--humans & birth. PMID- 2314320 TI - Acute dental caries, mental stress, immunity and the active passage of ions through the teeth. PMID- 2314321 TI - Carcinogenic optical rotation. AB - It is suggested that viral nucleic acid inserts in vulnerable regions of host cell DNA contribute to cell transformation by introducing 43 degrees of optical rotation at 425 nm, and that a carcinogenic event caused by DNA inserts and adducts is spurious electron ejection from important adenine molecules that may be far from insert/adduct sites. PMID- 2314322 TI - Pathogenesis of acute graft-versus-host disease after open heart surgery. AB - Acute Graft-versus-Host disease (GVHD) generally occurs after allogenic bone marrow transplantation and in immunocompromised patients who have received blood products containing viable lymphocytes. A recently recognized association is that of acute GVHD in the transfused post-open heart surgery patient. The factors that converge after open heart surgery that allow the engraftment and proliferation of donor lymphocytes are discussed and a hypothesis is developed to link the acute GVHD and open heart surgery. PMID- 2314323 TI - Isotopical positional correlations as a possible model for Benveniste experiments. AB - I suggest a hypothetic explanation of recently found 'memory effect' in water (water 'remembers' the presence of some biologically active molecules even when they are diluted to levels less then one molecule per total volume). My explanation is based on isotopic diversity water, namely that some positional correlations of stable isotope (H, D, 16O, 17O and 18O) might work as 'templates' of the originally dissolved molecules. These isotopic correlations are equivalent to the choice of a particular isotopic pattern out of the highly degenerate manyfold of potentially available patterns. This pattern is further reproduced at each next dilution level by some sort of 'locking-in' mechanism. Among possible physical candidates for such locking-in action is the polaronic self stabilization in non-linear media. PMID- 2314324 TI - A rapid evolution mechanism may contribute to changes in sex ratio, multiple birth incidence, frequency of auto-immune disease and frequency of birth defects in Clomid conceptions. AB - Under conditions favourable to the horizontal transmission of genetic material, a clomiphene isomer is hypothesized to encourage an alternate ovulatory route, with consequence for the sex ratio, multiple birth incidence, incidence of auto-immune disease, and frequency of malformations. PMID- 2314325 TI - Serine proteinase inhibitors on chromosome 14 and the genetics of familial chronic obstructive airways disease. AB - Environmental and genetic factors contribute to familial chronic obstructive airways disease. The genetic component could be polygenic or in some families be associated with one or two major genes. It is assumed that most cases of familial chronic obstructive airways disease are polygenic, but this conclusion is based on insufficient data. The use of linkage analysis using DNA probes for specific genes that may have a direct role in the disease process should facilitate our understanding of the genetics. Genetic deficiency of alpha1-antitrypsin is associated with predisposition to pulmonary emphysema. In the absence of alpha 1 antitrypsin deficiency I suggest that a study of serine-proteinase inhibitors on chromosome 14 may identify a significant proportion of families where only one major gene is important. PMID- 2314326 TI - DNA markers in genetic disease. PMID- 2314327 TI - "Random breath tests". PMID- 2314328 TI - Hyperthermia in the treatment of cancer. PMID- 2314329 TI - Publicity, police resources and the effectiveness of random breath testing. AB - Random breath testing (RBT) of drivers by the police was introduced in South Australia in 1981 at a very low level of enforcement. As there was no lasting effect on illegal "drink driving" the resources devoted to RBT were increased in 1987. In the months after this change police doubled the number of drivers tested by RBT. Concurrent with this change in the level of enforcement of RBT was an extensive publicity campaign, which warned drinking drivers of their increased risk of detection by RBT units. A roadside breath alcohol survey, conducted in metropolitan Adelaide late at night to evaluate the effect of these changes, showed a 34% reduction in the proportion of car drivers detected with a blood alcohol concentration at or above the legal limit of 0.08 g/100 mL. PMID- 2314330 TI - Predictive diagnosis for polycystic kidney disease using DNA markers. AB - Two families in which the gene for the common, autosomal dominant form of polycystic kidney disease (PKD1) was present were examined using flanking DNA markers. The 5'HVR probe detects a linked DNA marker 8 map units distal to the PKD1 gene in males and 1 unit distal to the PKD1 gene in females. The 24-1 probe detects another linked DNA marker 4 map units proximal to the PKD1 gene in males and 0.5 map units proximal to the PKD1 gene in females. When each marker is informative they can be used as a pair flanking the disease gene to follow accurately its transmission through families for presymptomatic or prenatal prediction. For an asymptomatic individual tested in one family, DNA studies reduced the 50% prior risk of carrying the disease gene to 0.006%. An affected woman in a second family was shown to be fully informative for the flanking markers. In a future pregnancy, it will be possible to modify the 50% prior fetal risk to either 0.008% or 99.99% depending on which maternal chromosome 16 is transmitted, and provided that no cross-over occurs between the flanking markers (probability, 1.5%). PMID- 2314331 TI - Reviewing the reviewers: a survey of institutional ethics committees in Australia. AB - Completed questionnaires were received from 89 (88%) of the 101 Australian institutions identified as having an ethics committee which reviewed research on human subjects. The majority (75%) of committees complied with national requirements to include a layman, a laywoman, a minister of religion, a lawyer and a medical graduate with research experience in their membership. On average, the committees considered 41 research protocols in the year from mid 1987 to mid 1988. The proposed projects were from the medical sciences, including health services and epidemiology research (80% of projects), and the behavioural and social sciences (20% of projects). Less than half the committees monitored research projects in progress as a general practice. Most of the monitoring that was conducted was based on a report from the researcher on the progress of the study. Although monitoring, frequency of meetings, selection of committee members, member involvement in the review of their own protocols and provisions for expedited review gave cause for concern, most committees were found to follow the national guide-lines. PMID- 2314333 TI - Death from myocardial infarction: what are the benefits of early arrival at hospital and thrombolysis? AB - The potential benefits of early hospital care in the event of myocardial infarction were investigated in a community-based study of all suspected cases of heart attack among people aged under 70 years in the Hunter Region of New South Wales. Between August 1984 and December 1985 acute care data were collected for 1029 cardiovascular events classified as definite myocardial infarction or sudden coronary death; 516 (50%) resulted in death within 28 days from the onset of symptoms and 325 of these deaths (63%) occurred outside hospital. Of 703 people who are known to have reached hospital alive 205 (29%) did so more than four hours after the onset of symptoms. At the time of the study fewer than 1% of patients received streptokinase. To estimate the potential benefits of increased medical care an optimistic scenario was considered in which patients who arrived at hospital more than four hours after the onset of symptoms received medical attention earlier and all eligible patients received thrombolysis. Based on the results of the Second International Study of Infarct Survival (ISIS-2), if streptokinase and aspirin had been used 14% of deaths would have been averted. If, in addition, patients had arrived at hospital earlier and received optimal benefit from thrombolysis another 13% of deaths could have been avoided. These results provide a broader perspective of the potential benefits of improved medical care than can be obtained from hospital-based studies that deal only with those heart attack victims who survive long enough to reach hospital alive. PMID- 2314332 TI - Shoulder shrug--a prognostic sign for recovery of hand movement after stroke. AB - A new clinical sign with prognostic significance for recovery of hand movements after stroke is described. Thirty-two patients with hemispheric cerebrovascular accident were assessed to determine whether the ability to shrug the hemiplegic shoulder at initial assessment correlated with the recovery of hand movements. The results of 29 of these patients with poor hand movements at initial assessment were analysed. Of 18 patients with absent shoulder shrug, only two patients (11%) showed return of good active movements in the involved hand at final evaluation, whereas eight (73%) of 11 patients who could shrug the hemiplegic shoulder at initial assessment went on to recover good movements in the hand (P = 0.00). In a subgroup of patients who demonstrated only synergistic flexion of fingers in the hemiplegic hand, one of five patients with absent shoulder shrug showed good hand movements at the final assessment in contrast to six of seven patients who initially could shrug the hemiplegic shoulder. Only one of 15 patients who showed total absence of hand movements at the initial assessment had a return of good hand movements. The data suggest that clinical assessment of shoulder shrug is a good prognostic indicator for recovery of voluntary movements in the hemiplegic hand especially when any hand movement, even if it is only synergistic finger flexion, is present at initial assessment. Total absence of hand movements at initial assessment is a poor prognostic sign. PMID- 2314334 TI - Prevention and treatment of postsurgical adhesions. PMID- 2314336 TI - Kilimanjaro, epistaxis and all that. PMID- 2314335 TI - Hyponatraemia due to the combination of hydrochlorothiazide and amiloride (Moduretic): Australian spontaneous reports 1977-1988. PMID- 2314337 TI - Group C streptococcal meningitis. AB - Group C streptococci have been infrequently described as human pathogens. A case of meningitis caused by Streptococcus dysgalactiae, in a 73-year-old man with alcoholic liver disease, was treated successfully with penicillin and chloramphenicol. PMID- 2314338 TI - The frequency of the common (delta F508) cystic fibrosis mutation in the Australian population. PMID- 2314339 TI - Risk factors for coronary heart disease. PMID- 2314340 TI - Boosting recruitment to breast screening programmes. PMID- 2314341 TI - Neisseria meningitidis in a school population in Queensland. PMID- 2314342 TI - The iris of the anarchist. PMID- 2314343 TI - Ketoprofen: possible idiosyncratic acute bronchospasm. PMID- 2314344 TI - Acute painful cellulitis caused by a Pasteurella pneumotropica-like bacterium in northern Queensland. PMID- 2314345 TI - Asbestos-related diseases. PMID- 2314347 TI - Medical tour of the USSR. PMID- 2314346 TI - Compound analgesics. PMID- 2314348 TI - To resuscitate or not. PMID- 2314349 TI - Fatal meningitis caused by chloramphenicol-resistant Haemophilus influenzae. PMID- 2314350 TI - [Drug use. Storage and administration references]. PMID- 2314352 TI - [Intestinal manifestations of renal cell cancer]. PMID- 2314351 TI - [Acral skin circulation following intra-arterial infusion of vasodilating substances in patients with intermittent claudication]. AB - The value of vasodilator drugs for the conservative treatment of peripheral arterial occlusive disease is widely questioned because clinical and experimental studies have shown paradoxical redistribution phenomena of blood flow in disfavour of an already ischemic peripheral circulation. This paper deals with acute effects of intraarterially infused prostaglandin E1 and buflomedil on the overall foot sole perfusion as well as its distribution patterns. Measurements were performed in patients with sufficiently compensated obstructions of the superficial femoral artery by means of dynamic fluorescein angiography. After i.a. infusion in general an increase of the total blood supply to the feet was found. However, in response to this common vasodilator effect in some patients apparently non-perfused circumscribed skin areas occurred which could never be observed under control conditions. With respect to these results the clinical value of vasodilator drugs as well as the meaning of such adverse redistribution phenomena are discussed from a pathophysiological and pharmacodynamical point of view. It is proposed that the therapeutical concept of pharmacological vasodilation should not be rejected in general. However, special attention should be paid to the development of steal effects. PMID- 2314353 TI - [Systemic mastocytosis]. PMID- 2314354 TI - [Acrokeratosis Bazex]. PMID- 2314355 TI - [Osteolysis in psoriatic arthritis?]. PMID- 2314356 TI - Use of a computerized postural sway measurement system for neurobehavioral toxicology. AB - The study of standing posture has been associated with nervous system functioning for over a hundred years. Measures of human standing ability have attracted some attention as indicators of neurotoxic insult. The use of postural sway measures as subclinical indicators of toxicity has not been regularly incorporated into most neurobehavioral test batteries, but the development of microcomputer controlled systems offers new possibilities. The mechanisms involved in controlling postural sway are discussed, as well as the various measurement techniques. In addition, studies involving the effects of some neurotoxic agents are cited. A postural sway measurement system that is noninvasive, has 1-2-minute test periods, provides immediate test results, and is relatively free of practice and motivation effects is described. Results present the normative characteristics of the sway parameters, a comparison of three data transformation techniques, and the effects of height and weight on the sway parameters. Power calculations were also performed to estimate the number of subjects needed to detect effects at both the 80% and 90% power levels. PMID- 2314357 TI - Neonatal ethanol exposure: functional alterations associated with cerebellar growth retardation. AB - The effects of alcohol exposure during the brain growth spurt on development and on behavioral assessments of functional alterations in the cerebellum were examined in the rat. Rat pups were exposed via an artificial rearing technique to either a 2.50% w/v or 2.15% w/v EtOH-milk formula during a period encompassing the brain growth spurt. An artificially reared control group and a suckle control group were also included. Peak blood alcohol concentrations for animals in the high and low dose alcohol exposure groups were approximately 300 mg/dl and 180 mg/dl, respectively. Reductions in brain minus cerebellum to body weight (BR C/BD) and cerebellum to body weight (C/BD) ratios were noted in animals from each of the alcohol-treated groups. Some catch-up growth in terms of brain mass was noted in animals from each of the alcohol-exposed groups. Animals exposed to alcohol during the neonatal period displayed deficits on several tests of balance and motor ability. Alcohol-exposed animals performed more poorly than controls when traversing two parallel horizontal rods and on tests of hindlimb and head elevation. No differences were noted in the ability to remain on a rotating drum. These results suggest that some of the behavioral consequences of neonatal ethanol exposure might be due to ethanol's actions on the cerebellum. PMID- 2314359 TI - Thermoregulatory effects of methanol in Fischer and Long Evans rats. AB - While methanol neurotoxicity has been studied for decades, there are very few data available on the thermoregulatory effects of methanol exposure. This paper will present the results of three studies designed to assess the effects of methanol on body temperature and behavioral thermoregulation in Fischer and Long Evans rats. The first study measured the onset of body temperature changes following methanol exposure. Following gavage of 3 g/kg methanol (20% w/v in saline), brain temperature (Tbr) of Fischer rats decreased 1.5 degrees C within 35 min. A similar volume of saline led to transient increases in Tbr. A second study assessed the time course of changes in body temperature by measuring colonic temperature (Tc) hourly following IP injection of saline or 1 or 3 g/kg methanol. The highest dosage of methanol caused a significant hypothermia in both Fischer and Long Evans rats. The hypothermia reached its nadir in both strains at 1-2 hours and partially recovered within the 6 hour experiment. The third study measured the effects of methanol on behavioral thermoregulation. Fischer and Long Evans rats were gavaged with saline or 1-3 g/kg methanol and placed in a temperature gradient. After 90 min in the gradient, rats of both strains which received 2 or 3 g/kg methanol had a significantly lower Tc than control rats. However, the methanol-treated rats remained in the cool end of the gradient and did not prevent the hypothermic effect of the alcohol. The absence of an observed effect on behavioral temperature selection suggests that methanol may interfere with thermal sensation. PMID- 2314358 TI - Enriched housing masks deficits in place navigation induced by neonatal monosodium glutamate. AB - Monosodium-L-glutamate (MSG)-induced behavioural deficits were examined under two housing conditions. Male Wistar rat pups were cross-fostered at birth and injected with MSG on days 2 to 11 postpartum. Control pups were injected with saline (Sal) of equivalent volume. Following weaning at day 25 the rats were allocated to either "enriched" (EC) or "impoverished" (IC) housing, thus forming four treatment groups: MSG-EC, MSG-IC, Sal-EC, and Sal-IC. Thirty-five days later all rats were tested in the open field and in the place navigation task. Multivariate analysis of variance (MANOVA) revealed a significant two-way interaction of the housing x drug variables. While the MSG-IC rats were deficient in the water maze, the performance of the MSG-EC approached that of saline injected controls. Although the Sal-IC rats developed higher body weights than the Sal-EC rats the MSG-EC and MSG-IC rats did not differ in body weight. The housing by drug treatment interaction was not apparent in the open field. PMID- 2314360 TI - Effects of repeated administration of soman on schedule-controlled behavior and brain in the rat. AB - The effects of repeated SC administration of soman on schedule-controlled performance and brain pathology were studied in the rat. Soman suppressed response rates in both components of a multiple fixed interval 50-sec fixed-ratio 25 (mult. FI 50-sec FR 25) schedule of reinforcement, although all animals revealed marked tolerance to repeated drug administration. Response rates generally recovered to baseline levels within 1-3 sessions. Three of the six animals studied, however, demonstrated marked deterioration of steady state schedule performance, particularly during the FI 50-sec component of the multiple schedule. Compared to untreated controls, all soman-treated animals exhibited pathological changes in brain. The most salient finding was glial cell proliferation in layer 4 and deep parts of layer 3 of the cerebral cortex. Glial cell proliferation was most marked in animals that exhibited deterioration of steady state schedule performance. PMID- 2314361 TI - Methylmercury effects on the social behavior of Macaca fascicularis infants. AB - Observations of the social behavior of Macaca fascicularis exposed in utero to methylmercury (MeHg) and nonexposed control infants were performed as part of a study of the toxic, reproductive and developmental effects of maternal MeHg intake. Infants were tested twice weekly from 2 weeks to 8 months of age. Data were summarized into 6 categories of social behavior and 7 categories of nonsocial behavior. Analysis of the most prevalent behavior indicated that MeHg exposed offspring exhibited a decrease in social play behavior and a concomitant increase in nonsocial passive behavior. The MeHg effect on social play behavior tended to decrease with age, while the group differences in nonsocial passive behavior tended to increase. The results indicate that maternal intake of MeHg during pregnancy can affect the social development of infant primates by suppressing social interactions and increasing nonsocial behavior. PMID- 2314362 TI - Microanalysis of ultrasound vocalizations of young rats: assessment of the behavioral teratogenicity of methylmercury. AB - An on-line real-time computer system for the analysis of ultrasound vocalizations of rats is presented. The calls of young rats are recorded by an ultrasound microphone, transformed by an amplitude envelope and a frequency to voltage converter, digitized and stored by a microcomputer. The data management and analysis of the recorded vocalizations are entirely automated, allowing a high throughput of experiments in a routine laboratory. The frequency values are analyzed with respect to number, duration, base-interval, and mean frequency of the calls. Also, the frequency distributions of the call to call intervals, the call durations and the ultrasound frequencies, as well as the power spectra of the frequency modulations, are calculated. This system was used for the assessment of the behavioral teratogenicity of methylmercury chloride. Wistar rat dams were treated with 0, 1.5 or 5 mg/l in their drinking water from two weeks prior to pairing until the end of the experiment. The ultrasound vocalizations of two female and two male offspring per litter were recorded on days 5, 7, 9, 11, 13, and 15 for one minute in a clean glass beaker cooled to 20 degrees C. Methylmercury treatment resulted in a developmental delay and an overall reduction in the number of calls, a shortening of the base-interval and the call durations, a flattening and shift of the frequency distributions, and an alteration in the development with age of the frequency distributions. The frequency modulations of the calls also differed, their power being lower (smaller frequency variation) on several occasions. PMID- 2314364 TI - Drivers with epilepsy. PMID- 2314363 TI - Neurobehavioral effects of the pyridinium aldoxime cholinesterase reactivator HI 6. AB - A series of neurobehavioral testing procedures was used to evaluate the behavioral effects of the pyridinium aldoxime cholinesterase reactivator HI-6 in male Sprague-Dawley rats. These procedures were fixed-ratio (FR) responding, shuttle-box conditioned avoidance response (CAR), conditioned taste aversion (CTA), drinking behavior, open-field exploratory behavior, negative geotaxis, and wire suspension time. Dose-response studies of HI-6 at dose-levels of 25, 50 and 100 mg/kg, or saline (IP) were evaluated. HI-6 disrupted FR responding in a dose dependent fashion, with significant effects occurring at doses of 50 and 100 mg/kg. The pattern of disruption was characterized by extended periods of nonresponding having an abrupt onset and offset. HI-6 produced CTA in a dose related manner, with significant effects at doses equal to those that disrupted FR performance. HI-6 did not alter CAR, drinking motivation, exploratory behavior, negative geotaxis, or wire suspension time. These data suggest that there may be a commonality in the underlying mechanism(s) for the disruption in FR performance and the induction of the CTA. This mechanism may relate to the presumed drug-induced adverse internal state inducing the CTA. PMID- 2314365 TI - Fair rural reimbursement. PMID- 2314366 TI - Are we equipped for the elderly boom? PMID- 2314367 TI - The limits of life and the limits of technology. PMID- 2314369 TI - Physiologic aging and nutritional status. PMID- 2314368 TI - The challenges of feeding the elderly. PMID- 2314370 TI - The other side of the story. PMID- 2314371 TI - Implications of a statewide survey of arthritis in Missouri. AB - The authors discuss the major findings of a survey intended to supply information to the Missouri Arthritis Program in order to reach its goal of improving the health status and quality of life of arthritis patients. PMID- 2314372 TI - An update on chymopapain for treating lumbar disc ruptures. AB - The author's experience in the use of chymopapain for the lysis of ruptured disc indicates that the drug is a valuable alternative to surgery. PMID- 2314373 TI - Intra-abdominal hemorrhage and shock due to uterine fibroid. AB - The authors describes a rare, but potentially life-threatening case of hemorrhage from a uterine fibroid. Prompt surgical management was essential for making the diagnosis and for saving the patient's life. PMID- 2314374 TI - Moth-associated dermatitis--Cozumel, Mexico. PMID- 2314375 TI - [Correlation between gastric microcirculation and mucosal injury after surgical therapy of esophageal varices]. AB - The correlation between gastric microcirculation and mucosal injury was studied in patients who underwent surgery for esophageal varices. Both mucosal and submucosal blood flow at the lower esophagus, gastric body and antrum was measured using hydrogen gas clearance method through endoscopy in 55 patients including 33 cirrhotics, 10 idiopathic portal hypertensive patients and 12 controls. In 20 cases with esophageal varices, 10 patients were treated with transabdominal esophageal transection (transection group) and 10 with left gastric vena caval shunt (shunt group). The patients with portal hypertension, showed a reduced blood flow in gastric mucosa but increased flow in the submucosa, as compared with the controls. When comparing the postoperative changes in gastric mucosal flow between the two groups, the transection group showed a reduction of mucosal flow by approximately 30% during surgery, and 20% for 4 weeks after operation. In shunt group, the mucosal flow was well preserved with reduction rate less than 10%. Postoperative mucosal injury was endoscopically and histologically found in almost all patients who showed a reduction rate of more than 20%. This study suggests that active protection against possible gastric mucosal lesion should be kept in mind in the setting of surgical therapy for esophageal varices. PMID- 2314376 TI - [Experimental studies of transcatheter portal embolization]. AB - The effects of transcatheter portal embolization (TPE) on energy charge (EC) and hepatic blood flow of the rat liver (HBF) were investigated. The antitumor effects on minimal tumor nodules inoculated into the rat liver via the portal vein were evaluated by the alphafetoprotein (AFP) levels and survival period after TPE. The EC of the embolized lobes was significantly decreased after TPE, as compared with the control groups, but was restored 3h later. The HBF of the embolized lobes was reduced 1h after TPE, but was restored in 1 day when TPE was performed by means of temporary embolus. When permanent embolus was used for TPE, decreased HBF persisted for at least seven days. On the other hand, HBF of the non-embolized lobes was not altered in both groups. When TPE was performed after TAE using temporary embolus, the intervals of 14 days were required for normal liver tissue to be preserved. TPE performed 3 days after inoculation of cancer cells into the rat liver caused prolongation of the survival period and decrease in the level of AFP. These results indicate that TPE does not produce marked damage to the liver and has antitumor effects on minimal tumor nodules. TAE followed by TPE may be useful for therapy of unresectable liver tumor. PMID- 2314377 TI - [Effect of thymectomy in myasthenia gravis]. AB - In order to examine the long-term effects of sternal splitting extended thymectomy in myasthenia gravis 42 patients were evaluated on an annual basis, beginning 12 months after surgery. The effects of surgery on the patients' myasthenic symptoms were as follows: 21.4% of the patients achieved complete remission, 61.9% showed improvement; in total 83.3% had palliation. There were no significant correlation among age, sex, Osserman type, pre-operative treatment and histological findings. Patients with long duration of the disease showed a statistically lower percentage of remission; the patients with complication after operation showed a lower percentage of palliation. The annual transition of the remission rate and the palliation rate were as follows: 11.8% of patients were in remission at 12 months after surgery; 16.1% at 24 months; and 17.4% at 36 months. Moreover 91.2% of the patients were palliated at 12 months after surgery; 90.3% at 24 months; 87.0% at 36 months; and 83.3% at 48 months. There was no significant difference in annual transition rates by age, Osserman type, pre operative treatment and histology by scattering matric analysis. There was significant differences in annual transition rates according to dyspnea, duration of the disease, sex and post-operative complication. PMID- 2314378 TI - [Reconstruction of the trachea invaded by advanced carcinoma of the esophagus, using the omental pedicle flap]. AB - The omental pedicle flap (OPF) was used for wrapping the plastic site of trachea involved in esophageal cancer in two cases. Though one of them developed an anastomotic dehiscence, the catastrophe was held off to the minimum. There were some disadvantages of the esophageal surgery for utilizing the omentum, compared to the other thoracic operations. It is the problem that the gastroepiploic artery should be shared to the gastric tube to some extent. But OPF was considered to be the best tissue in these particular cases. PMID- 2314380 TI - [Study of para-aortic lymph node metastasis of gastric cancer subjected to superextensive lymph node dissection]. AB - Para-aortic lymph nodes (n4), were dissected out to the technical extreme (superextensive lymph node dissection) from 129 gastric cancer cases, and were subjected to the histological study for metastasis. Following observations led us to the conclusions in reference to the significance of n4 node dissections on curability of surgery. 1) Among 25 cases with n4(+) metastasis n3 was free [n3( )] in 11 cases (44.0%). 2) ps(+) cancer presented high rate of n4(+) (31.5%). 3) n4(+) occurred irrespective of the location of the cancer, with particularly high rate of occurrence among CMA and cancers. 4) The rate of the metastasized lymph nodes to the total number of the n4 lymph nodes, was found low (34.9%) in cases with n3(-), and high (90.1%) with n3(+). 5) The cumulative survival rate of the cases with n4(+) was found significantly high with n3(-), as compared to n3(+) cases. The lymphatic drainage from the stomach seems more direct and/or more abundant to the n4 than to the n3 nodes. Such observation coincides with our experience that the n4 nodes are involved in metastasis in earlier timing and in higher incidence than n3 nodes. These results warn the present evaluation of curability in which the n4 node dissection is not performed. It is our opinion that the thorough dissection extended to the n4 nodes (superextensive lymph node dissection) is warranted, particularly in order to improve the curability of n3( )-n4(+) cases. PMID- 2314379 TI - [A case of obstructive jaundice caused by incarceration of pancreatic stones in the ampulla of papilla Vater]. AB - A very rare case of obstructive jaundice caused by the incarceration of pancreatic stones in the ampulla of papilla Vater is reported. A forty-eight-year old man, who had been taking alcohol daily for 10 years, was admitted to our hospital because of recurrent attacks of upper abdominal pain. Biochemical analysis demonstrated typical pattern of chronic pancreatitis. US, CT and ERCP showed a markedly dilated pancreatic duct and pancreatic calcifications. Cholecystolithiasis, or dilatation of the choledochus was not noted. Conservative treatment was performed under the diagnosis of chronic calcifying pancreatitis for one month. Then, obstructive jaundice, severe epigastralgia, and high fever occurred. Obstructive jaundice with sudden onset and existence of pancreatic stones suggested incarceration of pancreatic stones in the bile duct, and cephalic pancreaticoduodenectomy was performed. The largest pancreatic stone was incarcerated into the ampulla of papilla Vater. Histopathological analysis of the pancreas showed severe chronic pancreatitis. No report of the similar case can be found in the literature. Incarceration of pancreatic stones into biliary system might be very rare, however, should not be forgotten in differential diagnoses of obstructive jaundice in chronic pancreatitis patients. PMID- 2314381 TI - [Preoperative gastric acid secretion of gastric cancer patients and their prognosis]. AB - This study was performed to evaluate how preoperative gastric acid secretion in gastric cancer patients correlated their prognosis. The results are as follows. 1) The 5-year survival rates of patients with MAO = 0mEq/h, 0mEq/h less than MAO less than or equal to 7.0mEq/h and 7.0mEq/h less than MAO were 29.2%, 73.6% and 88.4%, respectively. There were significant differences among them. 2) The patients with 7.0mEq/h less than MAO had normal cellular immunity and low immunosuppressive glycoproteins in sera. These results suggest that gastric cancer patients who have a potency of normal gastric acid secretion with normal cellular immunity, or who have a potency of normal immunity with normal gastric acid secretion, have a good prognosis. PMID- 2314382 TI - [Gastric secretion in vagotomized stomach and transplant stomach in rat]. AB - The gastric phase of gastric secretion is well documented. The object of this study was to estimate the relationship between the host and the graft stomach in rats. Our findings revealed individual variations in total gastric secretion, while the mean secretory volume in syngeneic transplants remained relatively constant throughout the observation period. No significant changes in the secretion of free acid or pepsin were noted. Histologic studies were made of the myenteric nerve plexus and submucosal muscle. The creation of various models of gastric pouches and transplantation of the stomach have added valuable data to gastric physiology and transplant immunology. PMID- 2314383 TI - [Augmentation of cytotoxicity of regional lymph node lymphocytes of gastric cancer after intratumoral injection of OK-432]. AB - Although regional lymph node lymphocytes (LNL) are thought to be a barrier of the immunological surveillance, their natural cytotoxicity is strongly suppressed. In this study, an immunopotentiator OK-432 (10K.E.) was injected into gastric cancer lesions under endoscopy 1 week before operation, and the effects on the cytotoxicity of LNL were examined by single cell assay. This assay is characterized by assessment of killer cell frequency in preventing the killer cells from recycling by their fixation in agarose, and by direct microscopic observation of both binding and killing phases. NK sensitive cell line K562 was used as target cells. By intratumoral injection of OK-432, the killer cell frequency of LNL in 8 out of 20 cases was elevated to almost equal level as that of peripheral blood lymphocytes. In clinical stages these 8 cases belonged to early stages (stage I 7 cases, stage II 1 case). In LNL subsets of OK-432 injected cases, the percentage of OKT8 positive cells was decreased and the ratio of OKT4 and OKT8 was significantly increased compared with non-injected group. PMID- 2314384 TI - [31P nuclear magnetic resonance study of intrahepatic energy metabolism in acute liver failure]. AB - Changes in phosphorus metabolites and intracellular pH in acute liver failure induced by D-galactosamine (GAL) were evaluated non-destructively and continuously using 31P-NMR spectroscopy. Furthermore, changes in these parameters under ischemia were also examined. GAL(1.0g/kg) was injected intravenously to male Wistar rats. NMR measurements in perfused livers were performed with a GX 270FT NMR spectrometer (JEOL). Typical changes in 31P-NMR spectra were observed after GAL administration. ATP levels decreased to 57.4 +/- 12.4% at 12 hours and to 65.4 +/- 7.7% at 24 hours after the administration compared with that in control rats. Pi levels increased remarkably to 632.1 +/- 76.4% at 3 hours and recovered to 127.5 +/- 22% at 24 hours. NAD+/NADH and UDP-sugar levels gradually increased to 253.5 +/- 33.4 and 456.3 +/- 60.9%, respectively, at 24 hours. In GAL treated livers, ATP levels fell rapidly and Pi levels rose correspondingly during ischemia, and they rapidly recovered by reperfusion. The intracellular pH decreased to 7.16 +/- 0.032 from 7.38 +/- 0.065 at 3 hours after GAL administration. However, significant changes in pH were not observed until 24 hours. In GAL treated livers, slight changes in pH were observed under ischemia. These results indicate that 31P-NMR is a useful method to evaluate the damage of acute liver failure, and to diagnose liver diseases involving the intrahepatic energy metabolism. PMID- 2314385 TI - [Three-dimensional morphology of intrahepatic bile ducts in patients with intrahepatic gallstones]. AB - Eight livers surgically resected for intrahepatic gallstones were submitted to graphic reconstruction from serial histological sections to correlate the peculiar ductal changes with the pathogenetic aspects of this disease. Reconstruction was aided by a microcomputer system we have developed. Further, morphometric analysis was added to relate the obstruction of portal veins with parenchymal atrophy. Three-dimensionally, the ducts in these livers were strikingly transformed into a chain of ampullar dilatations interposed by either bending or strictures. Morphometrically, even a stenotic segment was wider than a corresponding normal one, showing that it was a relative stricture. The parenchymal lobule was atrophic or even completely destroyed due to the frequent thrombotic obstruction of portal veins about 0.5mm diameter. These 3-D morphology of intrahepatic bile ducts provided little evidence of congenital bile duct anomaly for the origin of intrahepatic gallstones. The basic ductal changes were dilations, alternated with "stenoses" that were more apparent than real. On the other hand, both the frequent obstruction of small portal veins and the lobular atrophy reflected a severely reduced portal blood flow. Not only the recurrent cholangitis that is apt to occur upon dilated ducts, but this functional incompetence of a stone-harboring, atrophic liver lobe strongly suggests a surgical indication for hepatic resection. PMID- 2314386 TI - [The role of alpha-tocopherol and allopurinol in lipid peroxidation and mitochondrial respiration in the ischemic rat liver]. AB - In the present study, the effects of alpha-tocopherol and allopurinol in liver ischemia and reperfusion injury on lipid peroxidation and mitochondrial respiratory function were investigated in rats. Ischemia was induced in the left and median liver lobes clamping the vessels for 90 minutes. After declamping reperfusion was continued for 60 minutes. Liver tissue was taken before and 90 minutes after ischemia and 60 minutes after reperfusion to measure lipid peroxides and mitochondrial respiratory function. In one group of rats alpha tocopherol (10mg/kg) was given intraperitoneally for three consecutive days preoperatively and in the other group allopurinol (50mg/kg) was given intravenously 10 minutes before ischemia. alpha-Tocopherol caused inhibition of increase in lipid peroxides at reperfusion and improvement in lowering of mitochondrial respiratory function. This improvement was less than previously reported, probably due to not only reperfusion injury but also ischemic injury. Allopurinol, on the other hand, caused neither such inhibition nor such improvement, suggesting the other source of oxygen-derived free radicals than xanthine oxidase system. PMID- 2314387 TI - Two distinct angiotensin II receptor binding sites in rat adrenal revealed by new selective nonpeptide ligands. AB - The nonpeptide angiotensin II antagonists Dup-89 and WL-19 displaced specific 125I-angiotensin II binding in rat whole adrenal in a clearly biphasic manner, indicating the presence of high (nanomolar) and low (micromolar) affinity sites, each representing approximately 50% of the total maximal number of binding sites. Displacement studies using sufficient concentrations of either antagonist to prevent binding to its respective high affinity site revealed that the high affinity binding sites for Dup-89 and WL-19 were distinct and corresponded to the low affinity site of the other. Both binding sites were also present in the adrenal capsule (cortex) and adrenal decapsulated (medulla) tissue. The two 125I angiotensin II binding sites were also differentiated by their sensitivity to dithiothreitol and the relative affinities of angiotensin II, angiotensin III, and their respective Sar1,Ile8- and Ile7-substituted antagonist analogs. Only Dup 89 (KB = 13 nM) was effective in antagonizing angiotensin II-stimulated aldosterone release from dispersed adrenal capsular cells, indicating that this functional response is mediated by an action upon the 125I-angiotensin II binding site at which Dup-89 has high affinity. Collectively, the data provide additional strong support for the presence of two distinct angiotensin II receptor subtypes in the rat adrenal. PMID- 2314388 TI - Characterization of the binding of [3H]Ro 41-1049 to the active site of human monoamine oxidase-A. AB - The novel reversible and selective inhibitor of monoamine oxidase-A (MAO-A) Ro 41 1049 [N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide HCl] shows inhibition characteristics similar to those of the structurally related reversible MAO-B inhibitors Ro 16-6491 and Ro 19-6327. In the present study, tritiated Ro 41-1049 was used as a high affinity ligand to study the binding characteristics of this inhibitor to MAO-A and its interactions with the enzyme. An homogeneous population of high affinity binding sites for [3H]Ro 41-1049 was found in membrane preparations from human frontal cortex and placenta (Kd = 16.5 +/- 1.4 and 64.4 +/- 19.2 nM, respectively). In frontal cortex the Bmax value for [3H]Ro 41-1049 (2.6 +/- 0.4 pmol/mg of protein) was about one third of the Bmax calculated for the MAO-B-selective ligand [3H]Ro 16-6491. The density of [3H]Ro 41-1049 binding sites in human placenta varied greatly in the different tissue samples investigated, showing an average Bmax of 101.7 +/- 36.5 pmol/mg of protein. Apparent binding equilibrium was reached after 1 hr of incubation at 37 degrees. At this temperature the binding was reversible, with a dissociation t 1/2 of about 35 min. At lower temperatures the radioactivity dissociation was much slower. Among the various drugs tested, only inhibitors of MAO-A were able to effectively prevent [3H]Ro 41-1049 specific binding. As previously reported for the MAO-B ligands [3H]Ro 16-6491 and [3H]Ro 19-6327, the analysis of the membrane-bound radioactivity showed that [3H]Ro 41-1049 was entirely recovered in the form of its aldehyde derivative, indicating that Ro 41-1049 was deaminated by MAO-A. The existence of a Ro 41-1049 adduct reversibly bound to the enzyme active site might explain the inhibition mechanism of this compound. The exposure of the radioligand-enzyme complex to NaBH3CN at pH 4.5 caused the irreversible covalent incorporation of about 70% of the specifically bound radioactivity into a 60-kDa polypeptide. This incorporation was dependent on the pH and on the amount of NaBH3CN added. The presence of MAO-A- but not MAO-B-selective inhibitors prevented the covalent incorporation of [3H]Ro 41-1049. The present results indicate that [3H]Ro 41-1049 is incorporated into a subunit of MAO-A, in the presence of NaBH3CN, and modifies a protein domain that is essential for the enzyme activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2314389 TI - Changes in expression of mRNA coding for glutathione S-transferase subunits 1-2 and 7 in cultured rat hepatocytes. AB - mRNA hybridizing to probes for glutathione S-transferase (GST) subunits 1 and 2 (probe pGSTr 155) and subunit 7 (probe pGSTr 7) has been measured by Northern blot analysis in adult rat hepatocytes both in conventional monoculture and in co culture with epithelial cells. In addition, several media conditions were used, namely with and without fetal calf serum (FCS) and with and without nicotinamide or dimethyl sulfoxide (DMSO). In monoculture, mRNA coding for subunits 1 and 2 was extensively reduced in the presence of FCS. In the absence of FCS, after an initial decrease, an increase of subunits 1 and 2 mRNA was noticed on day 6. When nicotinamide or DMSO was added to the medium, the GST subunits 1 and 2 mRNA level increased during the culture period. In co-culture, an initial reduction in levels of mRNA encoding subunits 1 and 2 was less marked and the values measured increased with co-culture time. Nicotinamide tended to reduce these mRNA levels, whereas DMSO increased them. In contrast, in conventional culture, mRNA encoding subunit 7 was expressed de novo and this induction was prevented by DMSO but not by nicotinamide. Similar results were obtained with co-culture. PMID- 2314390 TI - Pharmacological characterization of 5-hydroxytryptamine4(5-HT4) receptors positively coupled to adenylate cyclase in adult guinea pig hippocampal membranes: effect of substituted benzamide derivatives. AB - Adult guinea pig hippocampal membranes contain two 5-hydroxytryptamine (5-HT) receptors positively coupled with an adenylate cyclase. One is a typical 5-HT1A receptor and the second is a nonclassical 5-HT receptor that we previously proposed to call 5-HT4. Here, we show that 4-amino-5-chlor-2-methoxy-benzamide derivatives are agonists of 5-HT4 receptors in guinea pig hippocampal membranes. Their effects on the adenylate cyclase of these membranes are not additive with those of 5-HT but are additive with those of RU 24969, a typical 5-HT1 agonist. The effects of benzamides, as well as those of 5-HT, on 5-HT4 receptors are not blocked by 5-HT1, 5-HT2, or 5-HT3 antagonists except ICS 205 903, which does so with a low affinity (1 microM). The potency of benzamides (cisapride greater than BRL 24924 greater than zacopride greater than BRL 20627 greater than metoclopramide) is similar to their effect of 5-HT4 receptors positively coupled with an adenylate cyclase of fetal mouse colliculi neurons. PMID- 2314392 TI - Mechanisms of activation of phenacetin to reactive metabolites by cytochrome P 450: a theoretical study involving radical intermediates. AB - The cytochrome P-450-mediated activation of phenacetin (PHEN) to reactive intermediates by two hypothetical mechanisms has been studied by use of SV 6-31G ab initio energy and spin distribution calculations. In our calculations, the cytochrome P-450 enzyme system has been substituted by a singlet oxygen atom in order to reduce the computational efforts and to fulfill the requirements as to spin conservation. Both mechanisms are based on the currently increasingly accepted view that radical intermediates, formed via sequential one-electron steps, play a crucial role in the metabolic activation of substrates by cytochrome P-450. The first pathway is proposed to involve an initial abstraction of an electron and a proton from the alpha-methylene carbon atom in the ethoxy side chain and can explain the O-deethylation products paracetamol and acetaldehyde. In the second pathway, an initial abstraction of an electron and a proton from the nitrogen atom in the acetylamino side chain is proposed. The calculated spin densities of the formed nitrogen radical indicate that the unpaired electron is primarily localized at the nitrogen atom and to a smaller extent at the ortho- and paracarbon atoms relative to the acetylamino group. Radical recombination reactions between a hydroxyl radical and the spin delocalization-radicalized reactive centers of the nitrogen radical can explain the formation of the metabolites N-hydroxy-PHEN, 2-hydroxy-PHEN, and the arylating metabolite N-acetyl-p-benzoquinone imine (NAPQI), which forms a 3-(S glutathionyl)paracetamol conjugate in the presence of glutathione. NAPQI is proposed to be formed via intermediate formation of a hemiketal. Proposals are made for the decomposition of this hemiketal into NAPQI that are consistent with currently available experimental data on 14C- and 18O-labeled PHEN. PMID- 2314391 TI - Autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by an oxidative stress. AB - Pretreatment of cultured hepatocytes with the ferric iron chelator deferoxamine prevents the killing of the cells by tert-butyl hydroperoxide (TBHP). Incubation of the deferoxamine-pretreated hepatocytes in a serum-free medium containing only 0.25 nM iron restored the sensitivity of the cells to TBHP within 4 to 6 hr. An amino acid-free medium accelerated the restoration of sensitivity in parallel with an enhanced rate of degradation of 14C-prelabeled protein. By contrast, inhibitors of the autophagic degradation of protein, including chymostatin, 3 methyladenine, benzyl alcohol, colchicine, oligomycin, and methylamine, inhibited the restoration of sensitivity of deferoxamine-treated hepatocytes to TBHP in parallel with their inhibition of protein degradation. With chymostatin, 3 methyladenine, benzyl alcohol, and colchicine, there was a parallel dose dependency of both the inhibition of protein turnover and the inhibition of the restoration of sensitivity to TBHP. Ascorbic acid, known to specifically retard the autophagic degradation of ferritin, inhibited the restoration of sensitivity to TBHP without effect on the general rate of protein turnover. None of the agents studied had any protective effect on the toxicity of TBHP for hepatocytes that were not pretreated with deferoxamine. These data indicate that the autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by TBHP. PMID- 2314394 TI - Use of monoclonal antibodies in the detection of structural alterations occurring in lysozyme on heating. AB - Seven murine anti-hen egg-white lysozyme (HEL) monoclonal antibodies (MAbs), which recognize distinct epitopes of the native enzyme, were used as macromolecular probes to detect structural or conformational alterations occurring in HEL on heating at 95 degrees C, pH 5. As the interactions of the heat-treated HEL with its corresponding MAbs were carried out at room temperature, only irreversible structural and/or conformational alterations could be detected. The transformation of the native enzyme into its denatured form was followed electrophoretically and chromatographically. The denatured enzyme was more negatively charged at pH 8.4 and exhibited a longer retention time on reverse-phase HPLC than native HEL. Its specific catalytic activity was considerably lower than that of the native enzyme. Of the seven MAbs tested in competitive ELISA assays with native and heat-treated HEL only one, MAb D74.3, failed to recognize the heat-treated enzyme. This antibody, which is directed toward the active site region of the enzyme, was ineffective in inhibiting the catalytic activity of the heat-treated HEL using M. lysodeikticus as substrate. In contrast, the monoclonal antibody D1.3, which recognizes an epitope remote from the active site of HEL, inhibited the catalytic activity of the native as well as the heat-treated enzyme. The results indicate that the active site of HEL undergoes an irreversible structural alteration on heating for 2 hr at 95 degrees C, pH 5. No irreversible structural changes could be detected in the other regions of HEL recognized by the corresponding MAbs. PMID- 2314393 TI - Cysteine conjugate toxicity, metabolism, and binding to macromolecules in isolated rat kidney mitochondria. AB - The 14C-labeled, 35S-labeled, and unlabeled nephrotoxic cysteine conjugates S (1,2-dichlorovinyl)-L-cysteine, S-(2-chloro-1,1,2-trifluoroethyl)- L-cysteine, S (1,1,2,2-tetrafluoroethyl)-L-cysteine, S-(1,2,3,4,4-pentachlorobutadienyl)-L- cysteine (PCBC), and S-(1,1,2,3,3,3-hexafluoropropyl)-L-cysteine were synthesized and their toxicities were compared in isolated rat renal mitochondria. Inhibition of respiration, covalent binding to macromolecules, metabolism by mitochondria, metabolism by a purified cysteine conjugate beta-lyase (beta-lyase), and octanol/water partition coefficients were studied. All of the conjugates inhibited mitochondrial state 3 respiration. Only PCBC was found to uncouple oxidative phosphorylation. (Aminooxy)acetic acid, a beta-lyase inhibitor, blocked the effects of the conjugates on state 3 respiration except for the uncoupling effect of PCBC, which was not blocked. Binding of 35S label to macromolecules was observed after treatment with each of the 35S-labeled conjugates, and (aminooxy)acetic acid blocked the binding. The relative amounts of metabolism of the conjugates did not correlate well with their relative binding and toxicities, indicating some differential reactivity of metabolites and/or selectivity for binding targets. Some of the binding from 35S-labeled conjugates was removed by treatment with the disulfide-reducing agent dithiothreitol, suggesting that some of the binding was via mixed disulfides. The amount of dithiothreitol-sensitive binding differed among the conjugates. The metabolism of PCBC by permeabilized mitochondria, but not by a purified beta-lyase, was consistent with its relative toxicity and covalent binding, suggesting the involvement of other beta-lyase enzymes in the activation of PCBC to toxic species in mitochondria. PMID- 2314395 TI - Detection of specific antigens for ten serogroups of Clostridium difficile. AB - We previously described a serogrouping technique for Clostridium difficile based on slide agglutination with rabbit antisera raised against formol-treated cells. It allows the differentiation of ten serogroups, namely A, B, C, D, F, G, H, I, K and X. Each serogroup displays a specific profile with several distinctive bands by polyacrylamide gel electrophoresis (PAGE). In this study we investigated the common and specific antigenic determinants of the ten serogroups by immunoblotting. In a first experiment, whole cell proteins of the ten reference strains were separated by SDS-PAGE, transferred onto nitrocellulose membrane and immunoblotted against their homologous and heterologous antisera. Each serogroup was characterized by several common bands and one or two specific antigens which were proven to correspond to the lowest molecular weight distinctive band observed on PAGE profiles. New rabbit antisera were subsequently raised against the purified specific antigen obtained by electro-elution from polyacrylamide gels. Immunoblots were repeated with these new antisera: all reactions were serogroup specific except one minor cross reaction between C and F. The antisera still agglutinated the homologous strain without any cross agglutination, suggesting that the serogroup specific determinant is a surface antigen responsible for agglutination. PMID- 2314396 TI - Amplification of hepatitis delta virus RNA sequences by polymerase chain reaction: a tool for viral detection and cloning. AB - In this investigation we have evaluated the feasibility of using the polymerase chain reaction (PCR) for hepatitis delta virus (HDV) RNA detection, cloning and sequencing. Total RNA from HDV-infected liver and serum samples was purified and Moloney murine leukaemia virus (M-MLV) reverse transcribed. HDV cDNA was then directly amplified with Taq polymerase using three pairs of specific primers. It was possible to amplify a region of about 1200 bp in three partially overlapping fragments including the whole HDAg-ORF. A DNA fragment of the expected size was repeatedly obtained from an initial sample of less than 0.1 pg of liver RNA and from 10 pl of infected serum. An amplified fragment of 359 bp obtained by PCR from an infected woodchucks' liver was sequenced. The sequence was 91.8% and 98.6% identical to previously published HDV sequences. In addition, amplified and 32P-radiolabelled HDV sequences were shown to hybridize specifically to HDV RNA extracted from HDV-infected liver and serum. In conclusion this technique promises to be of great value in the appraisal of HDV infection, rapid synthesis of HDV probes and analysis of the genetic variability of the virus. PMID- 2314397 TI - Detection of Borrelia burgdorferi DNA by the polymerase chain reaction. AB - DNA amplification by the polymerase chain reaction (PCR) was used to detect DNA of the Lyme disease spirochaete Borrelia burgdorferi. Primers that specify the amplification of a 145 basepair DNA fragment of the OspA gene of B. burgdorferi were used. The amplification product was detected by gel electrophoresis and ethidium bromide staining or by hybridization to a radiolabelled oligonucleotide probe. The hybridization method was found to be more sensitive. As little as 50 fg of purified B. burgdorferi DNA could be detected by PCR. This corresponds to fewer than 50 spirochaetes. The specificity of PCR for B. burgdorferi was tested by using DNA from other organisms as templates for amplification. No cross reactivity was found. The data shown provide useful information for the development of a PCR-based diagnostic test for Lyme disease. PMID- 2314398 TI - [Value of the elastase-alpha 1-proteinase inhibitor complex in pediatric oncologic patients with fever]. AB - The elastase-alpha1-proteinase inhibitor complex (E-alpha 1-PI) is a well known, sensitive indicator of infection. The significance of this parameter was investigated in 12 febrile paediatric-oncological patients. With neutrophil counts greater than 500/microliters infections caused a definitive increase in E alpha 1-PI serving as an additional diagnostic parameter. E-alpha 1-PI provided no additional information in situations of sepsis with leukopenia and simultaneous agranulocytosis. In patients with metastatic tumours, the assay of E alpha 1-PI may differentiate between infection-related and tumour-related serological disturbances. PMID- 2314399 TI - [Experiences with specific screening for early detection of congenital adrenogenital syndrome with 21-hydroxylase defect]. AB - In Southern Bavaria over 32 months a total of 575 newborn babies was selectively screened for CAH due to 21-hydroxylase deficiency. Whenever one of the 3 key symptoms "failure to thrive", "ambiguous or atypical genitalia" and/or "positive family history" were present, a small plasma sample was drawn for the rapid and centralized radioimmunologic determination of 17-hydroxyprogesterone (17-OHP) and cortisol. Pathologically elevated 17-OHP plasma levels were found in 9 babies with CAH in whom adequate replacement therapy with gluco- and mineralocorticoids could be initiated without delay. On the basis of a mean birth rate of 60 000 per year a relatively low prevalence of 1:20 000 was calculated. It is likely that this is due to the fact that such a selective newborn screening program fails to detect the clinically normal male infants with simple virilizing CAH. PMID- 2314400 TI - [The current status and risk evaluation of the use of hormone preparations in food producing animals]. AB - Three groups of hormonal agents are currently in discussion for meat and milk production: sexual hormone active anabolics and beta-agonists, the latter acting as lipidmodulators to produce lean meat (for example, Clenbuterol, Salbutamol). Biologically active residues can result from illegal treatment only under exceptional circumstances. The analytical control measures, particularly for babyfood production, are of a very high standard in thr FRG and guarantee the safety of the products. The growth hormone that enhances milk yield has no importance as it is orally inactive. PMID- 2314401 TI - [Allergic reactions in treatment with L-asparaginase. Significance of specific IgE antibodies]. AB - The formation of specific IgE antibodies to L-Asp was studied in 27 children with ALL. Increased titers of specific IgE antibodies were significantly more frequent (p less than 0.001) prior to L-Asp infusions followed by allergic reactions than in those without reactions. After passive sensitization of basophile granulocytes of a healthy volunteer using patient's serum with the highest titers of specific IgE antibodies to L-Asp a significant release of histamine was observed after exposure of cells to L-Asp. In 1 of 8 patients with allergic reactions titers of specific IgE antibodies were elevated, while there was not detectable activation of the complement system. In conclusion, elevated titers of specific IgE antibodies to L-Asp are frequently detectable prior to L-Asp infusions which are associated with allergic reactions. In addition to activation of the classical complement pathway specific IgE antibodies and mediator release from mast cells may contribute to clinical symptoms. In a small number of patients this mechanism alone may be responsible for the allergic reaction. PMID- 2314402 TI - [Hypertelorism-hypospadias (BBB) syndrome. 2 additional family studies]. AB - We report on two unrelated families with the hypertelorism-hypospadias (BBB-) syndrome. The male index patients, 3 and 10 months old, respectively, have ocular hypertelorism, cleft lip and palate, high and broad nasal bridge and hypospadias. The patients' mothers, maternal grandmothers and one patient's sister show hypertelorism. In addition, we summarize the characteristics of previously published cases. PMID- 2314403 TI - [Intraspinal, extradural hemorrhage in a 7-year-old boy with hemophilia B]. AB - A 7-year-old boy with severe hemophilia B suffered an intraspinal extradural hemorrhage without preceding trauma. Since the age of 3 years the patient is HIV 1 positive. The actual hemorrhage caused a strong pain in the thoracolumbar area without signs of spinal cord compression. It was diagnosed by CT-scan. By early high dose factor-IX substitution the hemorrhage was stopped and no neurological complications occurred. The further substitution regime is described. PMID- 2314404 TI - [Intraspinal astrocytoma in a 3-year-old girl]. AB - A 3-year old patient with a spinal cord astrocytoma is presented. The clinical signs, diagnosis, neurosurgical, morphological results and prognosis are discussed. If there is any suspicion of an intraspinal abnormity, short-term neurological controls, somato-sensory evoked potentials and MRT of the spinal cord should be performed. PMID- 2314406 TI - Suppressing effect of antimutagenic flavorings on chromosome aberrations induced by UV-light or X-rays in cultured Chinese hamster cells. AB - Chromosome aberrations induced by UV-light or X-rays were suppressed by the post treatment with antimutagenic flavorings, such as anisaldehyde, cinnamaldehyde, coumarin, and vanillin. UV- or X-ray-irradiated surviving cells increased in the presence of each flavoring. X-ray-induced breakage-type and exchange-type chromosome aberrations were suppressed by the vanillin treatment in the G1 phase of the cell cycle and a greater decrease in the number of X-ray-induced chromosome aberrations during G1 holding was observed in the presence of vanillin. Furthermore, a greater decrease in the number of X-ray-induced DNA single-strand breaks was observed in the presence of vanillin. Treatment with vanillin in the G2 phase suppressed UV- and X-ray-induced breakage-type but not exchange-type chromosome aberrations. The suppression of breakage-type aberrations was assumed to be due to a modification of the capability of the post replicational repair of DNA double-strand breaks. These G1- and G2-dependent anticlastogenic effects were not observed in the presence of 2',3' dideoxythymidine, an inhibitor of DNA polymerase beta. Based on these results, the anticlastogenic effect of vanillin was considered to be due to the promotion of the DNA rejoining process in which DNA polymerase beta acts. PMID- 2314405 TI - [Treatment of respiratory distress syndrome in very small premature infants with bovine surfactant]. AB - In a clinical, uncontrolled study, bovine surfactant was administered intratracheally to 32 very low birth weight infants. In the first 18 patients, the dose was 20-40 mg/kg body weight (group 1, median birth weight 750 g) in the other 14 infants 40-50 mg/kg (group 2, median birth weight 840 g). The bovine surfactant was given, if the peak inspiratory pressures (PIP) were above 22-27 cm H2O depending on the infant's birth weight or whether the fraction of inspired oxygen (FiO2) was greater than 0.5. The FiO2 decreased from the pretreatment value of 0.7 to 0.46 after 1 hour, whereas PIP could not be lowered as rapidly as FiO2 (PIP from 29 to 26 cm H2O after 1 h). Surfactant treatment was more effective in group 2 comparing the reduction in FiO2 (delta FiO2 0.34 versus 0.16 in group 1 after 1 h), survival in group 2 was higher (71%) than in group 1 (56%). Our data are consistent with those of other groups using other natural surfactant preparations. PMID- 2314407 TI - Origin of aneuploidy in relation to disturbances of cell-cycle progression. I. Effects of vinblastine on mouse bone marrow cells. AB - Vinblastine (VBL) was tested in the mouse for induction of chromosome malsegregation in bone marrow cells. The occurrence of aneuploidy and polyploidy was correlated with cell-cycle kinetics measured by DNA labelling with bromodeoxyuridine (BrdUrd). Sister-chromatid exchanges (SCE) were also detected. A dose-dependent lengthening of the cell cycle was induced in the dose range of 0.9-4.5 mg/kg body weight, up to a complete inhibition of cell-cycle progression (100% of metaphases were arrested before completion of the first mitotic division following a recovery time of 18 h, compared with 8% in the controls). Both aneuploidy and polyploidy were induced. Aneuploid metaphases were grouped into 2 classes, those with no more than 2 extra chromosomes and those with 3-10 extra chromosomes. The frequencies of cells with severe aneuploidy and polyploidy increased considerably when second-generation cells were sampled at a recovery time of 24 h. This observation suggested that gross chromosome imbalances occur preferentially after a period of mitotic arrest, probably as a consequence of multipolar spindles or failure of proper spindle assembly. Non-disjunction of single chromosomes arises independently of the mitotic block. A slight increase in SCE frequency was observed only at a recovery time of 18 h. This study may provide information on the kinetics and mechanisms of origin of VBL-induced numerical aberrations in vivo. PMID- 2314408 TI - Cytogenetic effects of near ultraviolet radiation in normal and systemic lupus erythematosus lymphocytes. AB - We have conducted a study on the spontaneous and UV-A-induced frequency of chromosomal breaks and sister-chromatid exchanges (SCE) in purified lymphocytes from normal donors and from systemic lupus erythematosus (SLE) patients who were in clinical remission at the time of the study. Our results show that although SLE lymphocytes exhibit a higher frequency of spontaneous SCEs than controls, the rate of chromosomal breakage is comparable in the 2 groups. In both controls and patients, irradiation with UV-A (320-400 nm) increases the SCE values but does not significantly affect the frequency of chromosomal aberrations. PMID- 2314409 TI - Comparison of clastogenicity of inorganic Mn administered in cationic and anionic forms in vivo. AB - A comparison of the cytotoxic activity of cationic (MnSO4) and anionic (KMnO4) salts of inorganic manganese in the mouse in vivo indicated that the former was more strongly clastogenic than the latter. Mice were administered different doses of the salt orally over a period of 3 weeks. In general, both the frequencies of chromosomal aberrations in bone marrow cells and micronuclei were increased significantly by both salts. Sperm-head abnormalities showed a significant enhancement as well. The clastogenic effects were directly related to the concentrations used and were not markedly influenced by the duration of treatment. In view of the known affinity of Mn2+ for chromosomal components, it has been suggested that the effects were mediated by these ions produced directly from MnSO4 and indirectly from KMnO4 following conversion under acidic pH of the gastric juices. PMID- 2314410 TI - The effect of chemotherapy on the in vivo frequency of glycophorin A 'null' variant erythrocytes. AB - A human in vivo somatic cell assay based on the enumeration of variant erythrocytes lacking expression of an allelic form of the cell-surface sialoglycoprotein, glycophorin A, was applied to the study of blood samples from patients obtained prior to, during, and following chemotherapy for malignant disease in order to determine the effect of mutagenic chemical agents on the frequency of variant cells. In 22 patients assayed prior to therapy, the mean variant cell frequency was 11.9 per million, which was not significantly different from that observed in healthy controls. In an initial cross-sectional survey, blood samples were obtained at various times during and after therapy from 30 patients diagnosed with a variety of malignancies who were treated with one or more known mutagenic agents including adriamycin, bleomycin, cis-platinum, cyclophosphamide, dacarbazine, etoposide, lomustine, mechlorethamine, melphalan, mitomycin C, and procarbazine. Significant elevations in the mean frequency of variant cells over pre-therapy and normal levels were observed in samples obtained during and after therapy. In a time-series study, 14 breast cancer patients treated with CAF (cyclophosphamide, adriamycin, 5-fluorouracil), CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or VMF (vinblastine, methotrexate, 5-fluorouracil) adjuvant chemotherapy were sampled repeatedly during and after therapy. For the CAF and CMF patients an increase in the frequency of variant cells was observed with a lag in the appearance of induced variants after initiation of therapy; variant frequencies gradually increased during therapy reaching a maximum at or shortly after the end of therapy, then declined to near pre-therapy levels within 6 months. The maximum level of induced variants ranged from 2- to 7-fold over pre-therapy or normal levels depending on the combination of agents used. The breast cancer patients treated with both adriamycin and cyclophosphamide showed consistent elevations in the frequency of variant cells; patients treated only with cyclophosphamide showed lower and more variable elevations. The data demonstrate that mutagenic chemotherapy agents induce elevated levels of glycophorin A variant erythrocytes consistent with the hypothesis that variant cells result from somatic mutation. The elevations in variant cells were transient, suggesting that these agents primarily affect the rapidly cycling committed erythroid cell population. PMID- 2314411 TI - Evaluation of clastogenicity of formic acid, acetic acid and lactic acid on cultured mammalian cells. AB - Using Chinese hamster ovary K1 cells, chromosomal aberration tests were carried out with formic acid, acetic acid and lactic acid, and the relationship between the pH of the medium and the clastogenic activity was examined. The medium used was Ham's F12 supplemented with 17 mM NaHCO3 and 10% fetal calf serum. All of these acids induced chromosomal aberrations at the initial pH of ca. 6.0 or below (about 10-14 mM of each acid) both with and without S9 mix. Exposure of cells to about pH 5.7 or below (about 12-16 mM of each acid) was found to be toxic. When the culture medium was first acidified with each of these acids and then neutralized to pH 6.4 or pH 7.2 with NaOH, no clastogenic activity was observed. Using F12 medium supplemented with 34 mM NaHCO3 as a buffer, no clastogenic activity was observed at doses up to 25 mM of these acids (initial pH 5.8-6.0). However, it was found that about 10% of the cells had aberrations at pH 5.7 or below (27.5-32.5 mM of each acid). Furthermore, when 30 mM HEPES was used as a buffer, chromosomal aberrations were not induced at doses up to 20 mM formic acid and acetic acid (initial pH 7.0-7.1), and at doses up to 30 mM lactic acid (initial pH 6.6). In the initial pH range of 6.4-6.7 (25-32.5 mM of each acid), chromosomal aberrations were observed. The above results show that these acids themselves are non-clastogenic, and the pseudo-positive reactions attributable to non-physiological pH could be eliminated by either neutralization of the treatment medium or enhancement of the buffering ability. PMID- 2314412 TI - Distribution of nerve conduction velocities in acute thallium poisoning. AB - To assess the effects of thallium on the conduction velocities of faster and slower nerve fibers, the distribution of conduction velocities in sensory fibers of the median nerve was examined in a patient with acute thallium poisoning 2 and 11 months after the onset of symptoms. In the first examination, the patient showed evidence of a distal sensorimotor neuropathy and had an elevated urinary thallium concentration (3.5 mg/L); the conduction velocities of faster fibers were below the normal lower limit, whereas those of slower fibers were within normal limits. At the second examination, the conduction velocities of all faster and slower fibers increased and were within normal limits; clinical signs and symptoms of neuropathy almost disappeared. It is concluded that the conduction velocities of faster fibers significantly decrease in an early stage of acute thallium poisoning and recover following recuperation from the poisoning; those of slower fibers are minimally affected and then improve. PMID- 2314413 TI - Impairment of retrograde axonal transport in wobbler mouse motor neuron disease. AB - The earliest horseradish peroxidase (HRP) neuronal labeling (the fastest retrograde transport) was determined by histochemical techniques at various intervals after intramuscular HRP injection in wobbler mice and normal littermates. In the clinically impaired forelimb system, the retrograde transport rate was 150-170 mm/day in wobbler mice and 170-230 mm/day in controls. However, there was no statistical difference between the two groups. The neuronal HRP accumulation at the early intervals was significantly less in wobbler mice than controls, suggesting that the amount of HRP transport was diminished in each axon. For the clinically intact hindlimb nerves, the rate was normal in wobbler mice, but the amount of neuronal HRP was significantly increased. Retrograde axonal transport appeared to be affected in a differential fashion, depending on the extent of disease. PMID- 2314414 TI - Electrophysiological monitoring during lipomyelomeningocele resection. AB - Surgical resection of a lipomyelomeningocele carries a risk of injury to nerve roots in the cauda equina. We have devised a technique for combined spinal evoked potential and peripheral nerve compound action potential recording for intraoperative monitoring of this surgical procedure. We report the results of six cases where this technique was used. In each case, the monitoring prevented resection of viable neural tissue, and all six patients were neurologically unchanged postoperatively. PMID- 2314415 TI - Phosphorylase kinase isozymes and phosphorylase in denervated skeletal muscles. AB - The effects of motor denervation on levels of phosphorylase kinase isozymes and phosphorylase were investigated in rat epitrochlearis, hemidiaphragm, and soleus muscles. Amounts of the proteins were measured after quantitative immunoprecipitation and found to be decreased by as much as 70% 2 weeks after denervation. Unexpectedly, denervation had little, if any, effect on the relative proportions of the two phosphorylase kinase isozymes. Phosphorylase and phosphorylase kinase were decreased by essentially the same extent after denervation, and the effects of denervation were comparable in all three muscles. The decreases in these enzymes explain, at least in part, the marked alterations in glycogen metabolism that occur after motor denervation. PMID- 2314416 TI - Steroid-responsive electromyographic abnormalities in polymyalgia rheumatica. AB - Prior to definitive diagnosis, electrodiagnostic studies are often requested in patients with polymyalgia rheumatica to evaluate complaints of muscle aching, tenderness, and weakness. These studies are generally normal, although rare reports of electromyographic abnormalities in polymyalgia rheumatica exist. Two patients with polymyalgia rheumatica and electrodiagnostic findings consistent with diffuse denervation are described. Following steroid treatment, both patients experienced impressive clinical and electromyographic improvement. To explain this improvement, we hypothesize a steroid-responsive microvascular arteritis resulting in ischemic damage to axons of motor nerve terminal branches. PMID- 2314417 TI - Receptor-triggered polyphosphoinositide turnover produces less cytosolic free calcium in cultured dysgenic myotubes than in normal myotubes. AB - Myotubes prepared from mice with muscular dysgenesis (mdg) were used to further elucidate the putative role of inositol triphosphate (InsP3) in excitation contraction (E-C) coupling of skeletal muscle. The mdg mutation is characterized by an uncoupling of the E-C coupling. InsP3 production in normal and mdg/mdg myotube cultures and its relation to the levels of cytosolic free calcium were analyzed. Basal and ATP-stimulated levels of InsP3 were equal in normal and mdg/mdg myotube cultures. In contrast, the transient increases of cytosolic free calcium in mdg/mdg myotubes in culture were generally much lower than those in normal ones. This suggests that the defect in dysgenic myotubes does not rest on the InsP3 formation but on the InsP3-triggered transduction of excitation and/or the induction of calcium release from internal stores. PMID- 2314418 TI - Cortical magnetic stimulation in amyotrophic lateral sclerosis. AB - Forty patients with ALS underwent cortical magnetic stimulation. Twelve had marked pseudobulbar signs; in these motor evoked potentials (MEPs) could not be elicited. Mean MEP latencies in the others, who had predominantly lower motor neuron signs, measured 23.3 +/- 2.1 msec (thenar), 18.7 +/- 5.3 msec (EDC), and 13.4 +/- 2.9 msec (biceps), respectively. These values were significantly longer (P greater than 0.001) compared with normal values (n = 35), which measured 20.2 +/- 1.6, 14.2 +/- 1.7, and 9.4 +/- 1.7 msec, respectively. MEP amplitude was often markedly reduced (less than 15% of the M wave) compared with a normal mean of 39.5 +/- 13.0%. Overall abnormal MEPs (delayed, absent, or reduced in amplitude) approached 100%. It is argued that measuring central motor delay, which was not significantly different in the patients compared with normals, is subject to error in ALS. PMID- 2314419 TI - The effect of aging on cardiac autonomic and postganglionic sudomotor function. AB - Little quantitative information is available on the effects of age on peripheral autonomic function. We studied the effect of age on the heart rate (HR) responses to deep breathing and the Valsalva maneuver in 122 and 155 subjects, respectively, aged 10 to 83 years. The quantitative sudomotor axon reflex test (QSART) was determined in 114 subjects in the same age group. The HR responses were not different between the sexes, but a consistently significant regression with age was demonstrated in response to deep breathing and the Valsalva ratio. The QSART responses were significantly larger in male subjects and were generally lower in older subjects of both sexes but a significant negative regression with age was found only in female subjects. Cardiac vagal function is impaired with age, but postganglionic sympathetic function is little affected by age, suggesting selectivity of effects of aging on autonomic function. PMID- 2314420 TI - Dorsal interosseous neuropraxic compression syndrome. PMID- 2314421 TI - Association of the eosinophilia-myalgia syndrome with the ingestion of tryptophan. AB - We report on a series of three patients with an unusual syndrome of eosinophilia and myalgia associated with the oral ingestion of tryptophan that was recognized in New Mexico in October 1989. All three patients, who were women 37 to 44 years of age, had severe muscle pain, muscle weakness, mouth ulcers, and striking eosinophilia (more than 8 X 10(9) cells per liter). Other manifestations included fever, abdominal pain, dyspnea, skin rash, and elevated serum concentrations of aminotransferase and aldolase. The women had been taking tryptophan in doses of 1.2 to 2.4 g a day for three weeks to 2 1/2 years. The discontinuation of tryptophan and the initiation of glucocorticoid treatment resulted in improvement, but all three women were still symptomatic three to five months later. Tests for trichinosis and other parasites and for allergic and connective tissues disorders were negative, and serum immunoglobulin concentrations and erythrocyte sedimentation rates were normal. A muscle biopsy in one patient and biopsies of the vagina, liver, and other abdominal organs in another revealed eosinophilic infiltration, as well as the extracellular deposition of eosinophil granule major basic protein. All three patients had elevated serum and urinary levels of this protein and eosinophil-derived neurotoxin, indicative of eosinophil degranulation. The syndrome of eosinophilia and myalgia in association with the ingestion of tryptophan that was seen in these three patients is a newly recognized adverse effect of tryptophan ingestion. Our identification of this association in these patients led to the discovery of an epidemic of what is now called the eosinophilia-myalgia syndrome. PMID- 2314422 TI - A prospective study of obesity and risk of coronary heart disease in women. AB - We examined the incidence of nonfatal and fatal coronary heart disease in relation to obesity in a prospective cohort study of 115,886 U.S. women who were 30 to 55 years of age in 1976 and free of diagnosed coronary disease, stroke, and cancer. During eight years of follow-up (775,430 person-years), we identified 605 first coronary events, including 306 nonfatal myocardial infarctions, 83 deaths due to coronary heart disease, and 216 cases of confirmed angina pectoris. A higher Quetelet index (weight in kilograms divided by the square of the height in meters) was positively associated with the occurrence of each category of coronary heart disease. For increasing levels of current Quetelet index (less than 21, 21 to less than 23, 23 to less than 25, 25 to less than 29, and greater than or equal to 29), the relative risks of nonfatal myocardial infarction and fatal coronary heart disease combined, as adjusted for age and cigarette smoking, were 1.0, 1.3, 1.3, 1.8, and 3.3 (Mantel-extension chi for trend = 7.29; P less than 0.00001). As expected, control for a history of hypertension, diabetes mellitus, and hypercholesterolemia--conditions known to be biologic effects of obesity--attenuated the strength of the association. The current Quetelet index was a more important determinant of coronary risk than that at the age of 18; an intervening weight gain increased risk substantially. These prospective data emphasize the importance of obesity as a determinant of coronary heart disease in women. After control for cigarette smoking, which is essential to assess the true effects of obesity, even mild-to-moderate overweight increased the risk of coronary disease in middle-aged women. PMID- 2314423 TI - Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. AB - Abundant deposition of bronchoalveolar fibrin and fibronectin occurs during the exudative phase of the adult respiratory distress syndrome (ARDS), promoting hyaline-membrane formation and subsequent alveolar fibrosis. To explore the mechanisms that account for the persistence of bronchoalveolar fibrin and fibronectin, we compared the activity of urokinase, which is necessary for plasminogen activation and fibrin degradation, in cell-free bronchoalveolar lavage fluid from 8 patients with ARDS, 9 patients with acute pulmonary diseases other than ARDS, and 10 normal subjects. The mean level of urokinase activity in the lavage fluid from the patients with ARDS was 0.003 IU per milliliter of fluid (range, 0 to 0.008), which was significantly lower (P = 0.001) than the level in the fluid from either the patients with pulmonary diseases other than ARDS (0.118 IU per milliliter [range, 0.032 to 0.295]) or the normal subjects (0.129 IU per milliliter [range, 0.045 to 0.198]). The lavage fluid from all the patients with ARDS also had antiplasmin activity, which would promote the persistence of fibrin. A true decrease in urokinase activity was confirmed by the failure of the lavage fluid from the patients with ARDS to convert [125I]plasminogen to plasmin. Despite the low urokinase activity, immunochemical assays revealed normal levels of urokinase antigen in the fluid from the patients with ARDS, suggesting the presence of urokinase inhibitors. Inhibitors were demonstrated directly by a fibrin gel-underlay assay that detects complexes of urokinase with inhibitors. Plasminogen-activator inhibitor type 1 was the principal inhibitor identified. We conclude that increased antifibrinolytic activity due to both urokinase inhibitors and antiplasmins in the bronchoalveolar compartment of patients with ARDS contributes to the formation and persistence of hyaline membranes, a key component of alveolar histopathology in ARDS. PMID- 2314424 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 13-1990. A 23-year-old woman with primary amenorrhea, an abnormal karyotype, and bilateral inguinal masses. PMID- 2314425 TI - Tryptophan-induced eosinophilia-myalgia syndrome. PMID- 2314426 TI - The perils of obesity in middle-aged women. PMID- 2314427 TI - The yin and yang of fibrin in the airways. PMID- 2314428 TI - Case 4-1990: eosinophilic fasciitis. PMID- 2314429 TI - Predictive value of preoperative electrocardiographic monitoring. PMID- 2314430 TI - Plasma norepinephrine levels in patients with sleep apnea syndrome. PMID- 2314431 TI - Primary hyperoxaluria. PMID- 2314432 TI - Effect of inhaled furosemide on bronchial responsiveness to methacholine. PMID- 2314433 TI - Pneumocystis carinii choroiditis in patients receiving inhaled pentamidine. PMID- 2314434 TI - Access to information about physicians' credentials. PMID- 2314435 TI - Radiation as a risk factor for cancer of the breast. PMID- 2314436 TI - NMR--another cancer-test disappointment. PMID- 2314437 TI - Changes in the Journal. PMID- 2314438 TI - HLA-homozygous donors and transfusion-associated graft-versus-host disease. PMID- 2314439 TI - Diabetic end-stage renal disease. PMID- 2314440 TI - The effect of cyclosporine on the use of hospital resources for kidney transplantation. PMID- 2314441 TI - More on making sushi safe. PMID- 2314443 TI - Interviewing in the 1990s: the olive syndrome. PMID- 2314442 TI - Industry is responding to the crisis in biomedical-research brainpower. PMID- 2314444 TI - Kool-Aid colitis. PMID- 2314445 TI - Physicians' refusal of requested treatment. The case of Baby L. PMID- 2314446 TI - Proton nuclear magnetic resonance spectroscopy of plasma from healthy subjects and patients with cancer. AB - To evaluate the ability of proton nuclear magnetic resonance (NMR) spectroscopy to indicate the presence or absence of malignant disease, we analyzed plasma samples from 104 patients with untreated cancer of various types and from 164 healthy controls. All specimens were coded with random numbers, and the investigators were blind to patient category. A statistically significant difference (P less than 0.001) was found between the mean (+/- SD) line widths in the plasma samples from the controls (39.1 +/- 6.7 Hz) and the line widths in plasma from the patients with cancer (35.2 +/- 6.4 Hz). However, the values showed considerable overlap between the two groups. The average line widths in the 54 male (36.0 +/- 7.9 Hz) and the 110 female (40.5 +/- 5.6 Hz) controls were significantly different (P less than 0.001). Differences in the average line width were also found between 34 male controls 40 years old or older (33.9 +/- 6.5 Hz) and 20 younger men (39.6 +/- 8.8 Hz) (P = 0.008) and between 61 female controls 40 or older (38.8 +/- 5.7 Hz) and 49 younger women (42.5 +/- 4.7 Hz) (P less than 0.001). The average line widths in 36 women with cancer (35.5 +/- 6.8 Hz) and their controls matched for age and sex (39.0 +/- 6.3 Hz) were significantly different (P = 0.03) but again showed much overlap. In 29 men with cancer, the line widths were not different from those of controls matched for age and sex. We conclude that proton NMR spectroscopy is not generally reliable for the detection of cancer. Furthermore, our data demonstrate the importance of studying control groups matched for age and sex. PMID- 2314447 TI - Lack of efficacy of water-suppressed proton nuclear magnetic resonance spectroscopy of plasma for the detection of malignant tumors. AB - Water-suppressed proton nuclear magnetic resonance (NMR) spectroscopy of plasma has been proposed by Fossel et al. (N Engl J Med 1986; 315:1369-76) as a technique for detecting malignant tumors. In their analysis, plasma samples from patients with cancer were clearly distinguished from those of normal subjects by measuring and averaging the methyl and methylene line widths of plasma lipoproteins in NMR spectrums. To evaluate this diagnostic procedure further, we collected and analyzed by NMR spectroscopy 145 samples of plasma from patients who served as controls, most of whom were undergoing orthopedic or cardiac surgery (n = 66); patients with a variety of untreated malignant tumors (n = 25) or treated malignant tumors (n = 18); and patients with hyperplastic or "premalignant" diseases, such as benign prostatic hyperplasia and ulcerative colitis (n = 36). All the samples were coded, and NMR spectroscopy was performed without knowledge of the patients' clinical status. There were no significant differences in the NMR line widths among the four study groups (P greater than 0.05 for all pairwise comparisons). The specificity and sensitivity of this method for distinguishing the control patients (mean line width [+/- SD], 44.0 +/ 7.4 Hz) from those with untreated cancer (43.8 +/- 6.9 Hz) were poor, with a false positive rate of 52 percent (34 of 66) and a false negative rate of 56 percent (14 of 25). Inverse correlations of line widths with age (P less than 0.01) and with the plasma triglyceride level (P less than 0.001) were detected. We conclude that NMR spectroscopy of plasma is not an accurate test for the detection of malignant tumors. PMID- 2314448 TI - Yersinia enterocolitica O:3 infections in infants and children, associated with the household preparation of chitterlings. PMID- 2314449 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 14-1990. A 76-year-old man with a prosthetic aortic valve, staphylococcal sepsis, and a recent myocardial infarct. PMID- 2314450 TI - Antelopes die of "mad cow" disease. PMID- 2314451 TI - More radiation hazards. PMID- 2314452 TI - Nuclear safety. US response to Sellafield data. PMID- 2314453 TI - Transfer RNA. Synthetases gain recognition. PMID- 2314454 TI - Protein structure. Shuffling on this mortal coil. PMID- 2314455 TI - Metazoan phylogeny. Reassessing relationships. PMID- 2314456 TI - Scaling of sexual activity. PMID- 2314457 TI - Irradiation detection. PMID- 2314458 TI - Direct repeats in HSF binding sites. PMID- 2314459 TI - Muscarinic modulation of a transient K+ conductance in rat neostriatal neurons. AB - Neurons of the neostriatum are richly innervated by cholinergic neurons of intrinsic origin. Both pre- and post-synaptic muscarinic receptors mediate the effects of acetylcholine (ACh). Activation of these receptors is functionally significant, particularly in Parkinson's disease. Current-clamp studies indicate that muscarinic receptors serve to decrease the responsiveness of neostriatal neurons to excitatory inputs. Here we present evidence that this effect is caused, in part, by the muscarinic modulation of the A-current, a transient outward potassium current. The voltage dependence of this current suggests that normally it enhances spike repolarization and slows discharge rate, but does not affect 'synaptic integration'. We find that under the influence of muscarinic agonists, the voltage dependence of A-current activation and inactivation is shifted towards more negative membrane potentials and the peak conductance is increased. Therefore, at relatively hyperpolarized resting potentials, ACh transiently alters the functional role of the A-current, allowing it to suppress excitatory inputs and further slow the discharge rate. But at relatively depolarized resting potentials, ACh increases excitability by removing the A current through inactivation. PMID- 2314460 TI - Regulation and deregulation of cardiac Na(+)-Ca2+ exchange in giant excised sarcolemmal membrane patches. AB - A plasmalemmal Na(+)-Ca2+ exchange mechanism is an important electrogenic determinant of contractility in cardiac cells. As in other cell types, calcium influx by Na(+)-Ca2+ exchange is secondarily activated by cytoplasmic calcium and probably ATP, but these modulatory mechanisms are either absent or altered in isolated cardiac sarcolemmal vesicles. Involvement of a calcium-dependent protein kinase in exchange regulation has been suggested but not verified. Here I describe measurements of outward Na(+)-Ca2+ exchange current, corresponding to calcium influx, in giant excised sarcolemmal patches from guinea pig myocytes. The exchange current is stimulated by both calcium and Mg-ATP from the cytoplasmic face, evidently through separate mechanisms. Activation by cytoplasmic calcium takes place within seconds, is reversible, and does not require ATP. Stimulation by Mg-ATP reverses only slowly over greater than 10 min, or not at all. Unexpectedly, a substantial decrease in exchange current occurs during activation by cytoplasmic sodium, which seems to reflect an inactivation process rather than ion concentration changes or a 'first pass' exchange cycle. This apparent inactivation, and the modulations by cytoplasmic calcium and Mg ATP, are all abolished by brief treatment of the cytoplasmic surface with chymotrypsin, leaving the exchanger in a maintained state of high activity. Therefore, limited proteolysis deregulates Na(+)-Ca2+ exchange and could contribute to the loss of secondary regulation of the exchange in isolated sarcolemmal vesicles. PMID- 2314461 TI - Evolutionary transfer of the chloroplast tufA gene to the nucleus. AB - Evolutionary gene transfer is a basic corollary of the now widely accepted endosymbiotic theory, which proposes that mitochondria and chloroplasts originated from once free-living eubacteria. The small organellar chromosomes are remnants of larger bacterial genomes, with most endosymbiont genes having been either transferred to the nucleus soon after endosymbiosis or lost entirely, with some being functionally replaced by pre-existing nuclear genes. Several lines of evidence indicate that relocation of some organelle genes could have been more recent. These include the abundance of non-functional organelle sequences of recent origin in nuclear DNA, successful artificial transfer of functional organelle genes to the nucleus, and several examples of recently lost organelle genes, although none of these is known to have been replaced by a nuclear homologue that is clearly of organellar ancestry. We present gene sequence and molecular phylogenetic evidence for the transfer of the chloroplast tufA gene to the nucleus in the green algal ancestor of land plants. PMID- 2314462 TI - Relative helix-forming tendencies of nonpolar amino acids. AB - An important issue in understanding the relationship between protein sequence and structure is the degree to which different amino acids favour the formation of particular types of secondary structure. Estimates of the 'helix-forming tendency' of amino acids have been made based on 'host-guest' experiments, in which copolymers are made of the amino acid of interest (the 'guest') and a host residue (typically hydroxypropyl- or hydroxybutyl-L-glutamine). Recently, however, short alanine-based peptides were found to form stable monomeric helices in water, contrary to the result predicted from host-guest experiments. We have now measured the helix-forming tendency of five different nonpolar amino acids (Ala, Ile, Leu, Phe, Val) by substituting each in turn for alanine in a 17 residue alanine-based peptide and determining the extent of alpha-helix formation. Our results differ from those of host-guest experiments both in the degree of variation in helix-forming tendency of different amino acids, and in the rank order of the helix-forming tendency. We conclude that the helix-forming tendency of a particular amino acid depends on the sequence context in which it occurs; and the restriction of side-chain rotamer conformations is important in determining the helix-forming tendency. PMID- 2314463 TI - Bioassays with a microphysiometer. PMID- 2314464 TI - Monkey imports may be curtailed in US. PMID- 2314465 TI - AIDS. Mann's resignation causes uncertainty. PMID- 2314466 TI - Research with fetal tissue. PMID- 2314467 TI - Genetic linkage and psychiatric disease. PMID- 2314468 TI - Analogous alternative splicing. PMID- 2314469 TI - Origins of T-cell leukaemia virus. PMID- 2314470 TI - Copper-bottomed earwax. PMID- 2314471 TI - How secretion is inhibited. PMID- 2314472 TI - Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice. AB - Transgenic mice containing a human fetal (gamma-) or adult (beta-) globin gene linked to the beta-globin gene locus activation region (LAR) express the gene throughout development. By contrast, transgenic mice containing LAR linked to both a fetal and an adult globin gene display the normal developmental switch from fetal to adult gene expression. This suggests that the human fetal-to-adult globin gene switch is controlled through a mutually exclusive interaction between LAR and either the gamma- or beta-globin gene, resulting in the expression of only one gene at any given moment. PMID- 2314473 TI - Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. AB - The survival and functional maintenance of vertebrate neurons critically depends on the availability of specific neurotrophic factors. So far, only two such factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been characterized and shown to have the typical features of secretory proteins. This characterization has been possible because of the extraordinarily large quantities of NGF in some adult tissues, and the virtually unlimited availability of brain tissue from which BDNF was isolated. Both NGF and BDNF promote the survival of distinct neuronal populations in vivo and are related in their primary structure, suggesting that they are members of a gene family. Although there is little doubt about the existence of other such proteins, their low abundance has rendered their identification and characterization difficult. Taking advantage of sequence identities between NGF and BDNF, we have now identified a third member of this family, which we name neurotrophin-3. Both the tissue distribution of the messenger RNA and the neuronal specificity of this secretory protein differ from those of NGF and BDNF. Alignment of the sequences of the three proteins reveals a remarkable number of amino acid identities, including all cysteine residues. This alignment also delineates four variable domains, each of 7-11 amino acids, indicating structural elements presumably involved in the neuronal specificity of these proteins. PMID- 2314474 TI - Retinofugal fibres change conduction velocity and diameter between the optic nerve and tract in ferrets. AB - In earlier studies of central nervous fibre tracts, it was tacitly assumed that individual axons are relatively uniform along their length. In the retinofugal pathway in particular, axon diameter, myelin thickness and correlated conduction properties have been treated as constant throughout the optic nerve, chiasm and tract. We report here that the conduction velocities of fibres contributing to the early components of the compound action potential are significantly greater in the optic tract than in the optic nerve of ferrets, and also that the diameters of the largest retinofugal fibres increase from nerve to tract. This observation raises significant questions about the developmental mechanisms in the central nervous system that relate the axons, their diameters, and the glia with which they are myelinated. In addition, it indicates that studies that have relied on the constancy of conduction velocity along the retinofugal course may require reappraisal. PMID- 2314475 TI - Reverse hydrophobic effects relieved by amino-acid substitutions at a protein surface. AB - It is rare for amino-acid substitutions on the surface of proteins to have large stabilizing or destabilizing effects. Nevertheless, one substitution of this type, the Tyr 26----Cys mutation in lambda Cro, increases the melting temperature of the protein by 11 degrees C and the stability by 2.2 kcal mol-1. Here we show that the stability of Cro can be increased by many different amino-acid substitutions at position 26, with increasing stability showing a good correlation with decreasing side-chain hydrophobicity. As Tyr 26 is hyper-exposed to solvent in the Cro crystal structure, we suggest that wild-type and variant proteins with other hydrophobic side chains at position 26 are destabilized as a result of a reverse hydrophobic effect caused by the side chain being more exposed to solvent in the native than in the denatured state. PMID- 2314476 TI - The pictographic molecular paradigm. Pictorial communication in the chemical and biological sciences. AB - Chemistry, molecular biology and biology have turned into visive sciences in which ideas and information are communicated by artistic impressions and cartoons. These sciences have, in fact, become dominated by what we term the Pictographic molecular paradigm under which reality is acritically approximated by drawings of some kind. But it goes further than this and has both social and philosophical implications of which, we feel, there is insufficient general awareness. Important questions should be asked in connection with this way of doing science, including, for example, as to whether drawings of chemical formulae and graphical representation in biology meet the criterion of objectivity. This paper discusses some of the implications of the pictographic molecular paradigm and its limits and dangers. PMID- 2314477 TI - A comparison of enzymatic and heterogeneous catalysis. PMID- 2314478 TI - Sensory integration within temporally neutral systems states: a hypothesis. PMID- 2314479 TI - Muscarinic cholinoceptors in the human heart: demonstration, subclassification, and distribution. AB - In human atrial and ventricular myocardium, the muscarinic cholinoceptor (M cholinoceptor) populations were characterized by means of radioligand binding (with [N-methyl-3H]-scopolamine ([3H]-NMS) as the ligand) and functional experiments (negative inotropic effect of carbachol on isolated electrically driven right atrial and left papillary muscle preparations). (1) Binding of [3H] NMS to human atrial and ventricular membranes was rapid, reversible and saturable (KD-values: 0.5-1.0 nmol/l). The maximal number of [3H]-NMS binding sites, however, was approximately 2.5-fold higher in right and left atrial membranes (200-250 fmol [3H]-NMS specifically bound/mg protein) than in right and left ventricular membranes (80-100 fmol/mg protein). (2) M-cholinoceptor antagonists inhibited [3H]-NMS binding to right atrial and left ventricular membranes with steep, monophasic competition curves indicating interaction with a single class of binding sites. In both tissues the order of potency was: atropine greater than AF-DX 116 greater than hexahydrosiladifenidol (HHSiD) greater than pirenzepine. (3) On isolated electrically driven right atrial and left papillary muscle preparations (with force of contraction enhanced by 10(-5) mol/l isoprenaline), carbachol (10(-8)-10(-4) mol/l) caused concentration-dependent decreases in force of contraction; the pD2-value for carbachol was 6.65 +/- 0.09 (n = 8, atria) and 6.62 +/- 0.08 (n = 10, papillary muscles). In both tissues M-cholinoceptor antagonists antagonized the negative inotropic effect of carbachol with an order of potency: atropine greater than AF-DX 116 greater than HHSiD greater than pirenzepine, identical to that obtained in radioligand binding experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314480 TI - NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. AB - We studied the effects of the L-arginine analogue NG-nitro-arginine (L-NNA), in comparison with its D-isomer [D-NNA), on endothelium-dependent dilations of rabbit femoral arteries (RFA) and on the release of endothelium-derived relaxant factor (EDRF) from native and cultured endothelial cells. In addition, we examined the effects of L- and D-NNA on the L-arginine- and NADPH-dependent synthesis of nitric oxide (NO) in the cytosol of porcine aortic endothelial cells. L-NNA enhanced the noradrenaline-induced contraction of endothelium intact, but not of endothelium-denuded segments of RFA, indicating an inhibition of basal EDRF release. L-NNA also inhibited significantly the endothelium dependent dilations to acetylcholine (ACh). Both effects of L-NNA were attenuated by L-arginine. L-NNA rapidly inhibited the release of EDRF from cultured and native endothelial cells stimulated with thimerosal or ACh. L-NNA concentration dependently and reversibly antagonized the L-arginine- and NADPH-dependent activation of a purified soluble guanylate cyclase (GC) by cytosol from freshly harvested porcine aortic endothelial cells, suggesting a direct competition between L-NNA and L-arginine at the level of endothelial NO-synthesis. D-NNA was ineffective in all instances. These results prove L-NNA to be a stereospecific inhibitor of the cytosolic NO formation from L-arginine in endothelial cells. Therefore, L-NNA will be a useful tool to elucidate the molecular mechanism of mammalian NO synthesis. PMID- 2314481 TI - Intra- and extraluminally-applied acetylcholine on the vascular tone or the response to transmural stimulation in dog isolated mesenteric arteries. AB - Acetylcholine applied extraluminally to isolated, perfused dog mesenteric artery segments produced an endothelium-dependent depressor response when the perfusion pressure was raised by continuous infusion of noradrenaline; the potency was 1/30 to 1/60 that of intraluminal acetylcholine. Contractions induced by transmural electrical stimulation were attenuated by treatment with intra- and extraluminal acetylcholine; the inhibitory effect of intraluminal acetylcholine was greater than that of extraluminal acetylcholine. Removal of endothelium did not significantly alter the inhibitory effect. In mesenteric artery strips with endothelium, treatment with oxyhaemoglobin suppressed the relaxant response to acetylcholine but did not influence the inhibitory effect of acetylcholine on stimulation-evoked contractions. Acetylcholine reduced the 3H-overflow and contraction of superfused mesenteric artery strips, preloaded with 3H noradrenaline, response to transmural stimulation. By the use of bioassay (dog femoral artery segment with endothelium/coronary artery strip without endothelium), the release of EDRF was first determined in the perfusate, which was introduced to dog mesenteric artery strips loaded with 3H-noradrenaline. The 3H-overflow and contraction caused by the stimulation were not attenuated by EDRF and were also observed following treatment with superoxide dismutase. Inability of the perfusate to reduce the stimulation-evoked 3H-overflow was also observed when the donor and assay tissues were treated with superoxide dismutase. It may be concluded that the inhibition by acetylcholine of the release of neuronal noradrenaline is not dependent on endothelium. Extraluminally applied acetylcholine would reach the endothelium and release EDRF, and intraluminal acetylcholine is presumed to act directly on prejunctional muscarinic receptors; however, acetylcholine appears to cross the medial layer more efficiently from intima to adventitia than in the reverse direction. PMID- 2314482 TI - Mechanisms of the release of 3H-noradrenaline by dimethylphenylpiperazinium (DMPP) in the rat vas deferens. AB - In the rat vas deferens, DMPP is a substrate of uptake1 (Km = 11.5 mumol/l). After block of vesicular uptake, monoamine oxidase and catechol-O-methyl transferase, after loading of the tissue with 3H-noradrenaline, and in calcium free solution (i.e., when axoplasmic 3H-noradrenaline levels were high and when depolarization-induced exocytotic release was impossible), DMPP induced a pronounced outward transport of 3H-noradrenaline. On the other hand, when, in similar experiments, vesicular uptake and monoamine oxidase were intact (i.e., when axoplasmic 3H-noradrenaline levels were low), DMPP induced very little outward transport of 3H-noradrenaline. This discrepancy indicates that DMPP has little ability to mobilize vesicularly stored 3H-amine. When the medium contained calcium (catechol-O-methyl transferase inhibited, all other mechanisms intact), 100 (but not 10) mumol/l DMPP induced a hexamethonium-sensitive release of 3H noradrenaline of short duration. Hence, in the presence of extracellular calcium, 100 mumol/l DMPP elicits exocytotic release via activation of hexamethonium sensitive nicotinic acetylcholine receptors. DMPP inhibits the monoamine oxidase of rat heart homogenate with an IC50 of about 100 mumol/l. PMID- 2314483 TI - Propranolol inhibits nonexocytotic noradrenaline release in myocardial ischemia. AB - Ischemic induces a nonexocytotic noradrenaline release in the heart, which leads to high and potentially harmful interstitial noradrenaline concentrations. The effect of beta-adrenoceptor antagonists on noradrenaline release in ischemia has been investigated in the present study. DL-Propranolol (1-100 mumol/l) concentration-dependently reduced noradrenaline release during 20 min of global and total ischemia in the perfused rat heart. Other beta-adrenoceptor blocking agents such as atenolol, metoprolol, and timolol (10 mumol/l each), however, did not share this effect. Moreover, both stereoisomers of propranolol were equipotent in suppression of ischemia-induced noradrenaline release, indicating a property of propranolol independent from interaction with beta-adrenoceptors. The well known local anesthetic action of propranolol was not likely to cause its inhibitory effect on ischemia-induced noradrenaline release, as lidocaine (10 mumol/l) did not affect noradrenaline overflow in ischemia. The effect of propranolol was further examined in cyanide intoxication, an experimental model of energy depletion. In this experimental setting the release of dihydroxyphenylethyleneglycol--the major neuronal metabolite of noradrenaline- served as indicator of increased axoplasmic noradrenaline levels which are present during nonexocytotic noradrenaline release. In cyanide intoxication DL propranolol also reduced noradrenaline overflow but did not affect release of dihydroxyphenylethylene glycol. The latter finding suggests an interaction of propranolol with the neuronal membrane transport of noradrenaline. In ischemia and cyanide intoxication, transport of noradrenaline across the plasma membrane is known to be driven by the noradrenaline carrier (uptake1) working in reverse of its normal direction--from inside to outside. Consequently, inhibitors of the noradrenaline carrier like desipramine were shown to suppress nonexocytotic noradrenaline release in ischemia and cyanide intoxication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314484 TI - Anxiogenic-like action of caerulein, a CCK-8 receptor agonist, in the mouse: influence of acute and subchronic diazepam treatment. AB - Effects of caerulein, a cholecystokinin octapeptide (CCK-8) receptor agonist, on exploratory activity of mice were investigated. Exploratory and locomotor activity of animals were measured using elevated plus-maze and open field tests. The systemic administration of caerulein at non-sedative doses (100 ng/kg-1 micrograms/kg i.p.) resulted in a significant decrease in the exploratory activity of mice. This effect was completely blocked by proglumide, a CCK-8 receptor. Acute treatment with low doses (0.1-0.75 mg/kg i.p.) of diazepam did not attenuate the anxiogenic-like effect of caerulein, but at more high doses of diazepam the coadministration depressed locomotor activity in mice. After subchronic diazepam treatment (2.5 mg/kg once a day, 10 days, i.p.) tolerance was developed toward the sedative effect of diazepam, and 72 h after withdrawal of the drug the animals showed increased anxiety in the plus-maze test. 30 min after the last injection procedure the anxiogenic-like effect of caerulein (500 ng/kg i.p.) on exploration was absent in both diazepam or vehicle groups. However, 72 h after the last pretreatment injection caerulein (500 ng/kg i.p.) reduced significantly the exploratory activity in control group, whereas it was inactive after diazepam withdrawal. The results obtained in this study support the hypothesis that endogenous CCK-8 an CCK-8 receptors are involved in the neurochemistry of anxiety and the anxiolytic action of benzodiazepine tranquillizers. PMID- 2314485 TI - Endothelium-dependent relaxant action of platelet activating factor in the rat mesenteric artery. AB - Vasorelaxant action of platelet activating factor (PAF) was examined in perfused mesenteric vascular beds and mesenteric artery strips isolated from rats. PAF caused a dose-dependent vasodilation of norepinephrine-contracted mesenteric vascular bed, which was sensitive to CV-3988, a PAF antagonist, but insensitive to tetrodotoxin, atropine, propranolol and indomethacin. PAF also caused a relaxation of phenylephrine-contracted mesenteric artery strips at above 3 X 10( 12) M. Much higher concentrations of PAF were required to relax the aorta, carotid and pulmonary arteries. The PAF- and acetylcholine (ACh)-induced relaxations of mesenteric artery were dependent on the presence of endothelium and were inhibited by either hydroquinone and methylene blue, which inhibit the action of endothelium-derived relaxing factor (EDRF), or L-canavanine, which inhibits the formation of nitric oxide from L-arginine. Phospholipase A2 inhibitors such as quinacrine and ONO-RS-082 abolished the relaxation induced by ACh but did not affect that by PAF. Thus, PAF induces a vasorelaxation by releasing EDRF from endothelial cells as ACh does, although the pathway to produce the substances by PAF may be different from that by ACh. PMID- 2314486 TI - [Too weak with laughing]. PMID- 2314487 TI - [Rhonchi and crepitations: nomenclature and interpretation]. PMID- 2314488 TI - [Endobronchial hamartoma; a benign mesenchymal tumor]. AB - In this review the histological and clinical features of 12 endobronchial hamartomas seen between 1960 and 1987 are presented. All patients were men; the mean age was 54.0 years. Nine patients presented with pulmonary symptoms, most frequently cough. All lobes were affected, with a slight preponderance in the left upper lobe. Surgical treatment was given to 10 patients. In the other 2 cases bronchoscopic resection was preferable. There were no complications due to therapy. No recurrences were noted. This lesion should be regarded as a true neoplasm, in view of the clinical and histopathological characteristics. PMID- 2314489 TI - [Relationship between perioperative anxiety and postoperative recovery]. AB - One day before surgery and three days postoperatively, 118 cholecystectomy patients were investigated by means of several self-report anxiety question(naire)s. On the basis of these, the patients were assigned to either the category more anxious postoperatively (A+) or the category less anxious postoperatively (A-). A+ patients rated preoperatively lower and postoperatively higher on the anxiety-question(naire)s than A- patients, and they stayed longer in hospital postoperatively. PMID- 2314490 TI - [Registration and prevention of hospital infections in a general hospital]. AB - Active surveillance in a 270-beds general hospital in the period 1984-1988 yielded 1,547 episodes of hospital-acquired infections among 26,079 patients admitted, i.e. 5.9 infections per 100 admissions (5.1 infections/1,000 days in the hospital). Infections of the urinary tract (3.0/100 admissions), surgical wounds (1.0%), the respiratory tract (0.8%) and bloodstream infections (0.5%) predominated. The incidence of infections was highest among patients of 75 years and older (13.0%), lowest in the age group 1-14 years (1.2%). Escherichia coli, Staphylococcus aureus, enterococci and coagulase-negative staphylococci were isolated most frequently. Specific measures to limit the occurrence of urinary tract infection resulted in a decline in the rate of hospital-acquired infections, from 7.6% in 1984 to 4.9% in 1988 (35.5%). We conclude that active surveillance of hospital-acquired infections contributes to our awareness of these infections and provides the basis for preventive action. (Micro)computers constitute important aids for these activities. PMID- 2314491 TI - [Aids caused by HIV-2 in The Netherlands]. AB - In four patients in Rotterdam AIDS was diagnosed, and it was subsequently demonstrated that they were infected with HIV type 2. One of the patients was an immigrant from the Cape Verde islands, two of the others had heterosexual contacts with persons of this area, and the fourth patient was a male homosexual without known contacts with Africans. The Cape Verde islands are one of the areas in which HIV-2 infection occurs, and because of immigration into The Netherlands and in particular to Rotterdam, the possibility of HIV-2 infection should be considered in persons of this population group and their sexual contacts. Furthermore, problems with serologic investigations should be avoided by the application of HIV-2 specific confirmatory assays. PMID- 2314492 TI - [Liver metastases: a death sentence?]. PMID- 2314493 TI - [Cytostatic treatment of patients at home]. PMID- 2314494 TI - [Maxillary sinusitis in children]. AB - In children with nasal discharge the distinction between the group with a diagnosis of rhinitis and the group with a diagnosis of sinusitis was vague. Anamnestic data and findings at physical examination were not significantly different. There was hardly any relation between radiographic and echographic findings, the nature of the irrigation fluid, and isolation of pathogenic or non pathogenic bacteria from cultures of nasal or sinus secretions. In our opinion there is no clearcut difference between rhinitis and simple sinusitis (i.e. mucositis of the maxillary sinus without empyema). Nor is this therapeutically relevant because both conditions are mostly features of a respiratory tract infection. It is therapeutically important, however, to differentiate between sinusitis without and sinusitis with empyema. The latter requires special treatment. None of the patients studied had a sinusitis with empyema. When a child has running nose there is no reason to look for a sinusitis when there are no clinical symptoms of empyema. PMID- 2314495 TI - [The epidemiology of AIDS in Amsterdam, 1982-1988]. AB - The results are reported of AIDS monitoring in Amsterdam in the period 1982-1988. Males with homosexual contacts are the principal risk group followed by the fast growing group of users of intravenous drugs. Transmission of the human immunodeficiency virus to the heterosexual population will occur mostly via sexual contacts with users of drugs. An investigation of the degree of underreporting in Amsterdam revealed 23 unreported patients (5.7% of the cumulative total). The median duration of survival of AIDS patients increased: 1982-1985, 9 months, 1986, 12 months, 1987, 16 months. Two-year survival of patients in the periods 1986 and 1987 was practically the same, however. It is assumed that at the end of 1991, 1124 AIDS patients domiciled in Amsterdam will have been diagnosed. PMID- 2314496 TI - [Regional differences in vitamin K administration to a newborn infant]. PMID- 2314497 TI - [Health services research on the move]. PMID- 2314498 TI - [Limitations to medical ability]. PMID- 2314499 TI - [Current treatment of children with chronic juvenile arthritis]. PMID- 2314500 TI - [Finally action against passive smoking]. PMID- 2314501 TI - [Aids research proposals]. PMID- 2314503 TI - [Ritchie's scale of arthritis or: rheumatology prematurely as clinimetrics]. PMID- 2314502 TI - [Thrombotic thrombocytopenic purpura: a benign disease with a very severe acute phase]. PMID- 2314504 TI - [Do not underestimate prevention!]. PMID- 2314505 TI - [The surgical treatment of the Pancoast tumor]. AB - A retrospective study was made of eight patients who underwent operation in the period 1974-1987 because of a Pancoast (pulmonary sulcus) tumour. Of the five patients still alive, three have had no local recurrences for 15, 4 and 2 years, respectively, after the operation. Data from this investigation and from the literature confirm that the absence of metastases in mediastinal lymph nodes, and use of preoperative irradiation may have a favourable effect on the prognosis. The best result is achieved with preoperative irradiation followed by 'en bloc' resection of the affected pulmonary lobe, the tumour-infiltrated chest wall and, if necessary, part of the sympathetic trunk and the plexus brachialis inferior. Emphasis is laid on the importance of early recognition of the tumour in case of aspecific shoulder and arm symptoms. PMID- 2314506 TI - [The course of illness in ulcerative colitis]. AB - The data of 301 ulcerative proctitis/colitis patients, with a mean follow-up of 10 (1/2-26) years were analysed retrospectively. In 84 patients (28%) the diagnosis was made in this hospital (non-selected group), the other 217 patients were referred from other hospitals with an established diagnosis of ulcerative colitis. At any time after the fifth year of illness approximately 55% of the non selected patients were free of symptoms, for the referred patients this proportion was 30%. In one half of the cases the inflammation started as a proctitis, almost 60% of these progressed to colitis later. Fourteen patients (5%) had a toxic megacolon, and a colon carcinoma developed in 9 patients (3%) on average 13 years after the first symptoms of colitis. We recorded 9 colitis related deaths. Fifty patients (17%) underwent a colectomy, mostly because of failure of conservative therapy. PMID- 2314507 TI - [Lithium in the treatment of depressed elderly patients]. AB - In the geriatric department of a Dutch psychiatric hospital the charts of 65 patients treated with lithium for depression were reviewed. We assessed efficacy and adverse effects. The sample included 65 patients, 12 men and 53 women, mean age 77 (64-91) years. A complete or partial response was seen in 30 out of 43 patients (70%) treated with lithium in addition to a cyclic antidepressant. Six out of 22 patients treated with lithium as a sole antidepressant responded completely or partially. During lithium therapy 16 patients suffered from severe adverse effects. In our view and in spite of severe adverse effects, with expert monitoring lithium can be of value in the treatment of (very) old and depressed patients. PMID- 2314508 TI - [Fractures of the extremely atrophic mandible]. AB - Fracture treatment of the extremely atrophic mandible is a challenge to the surgeon because of the special problems and complications. A reliable method is the internal fixation technique with multiple split rib grafts. By use of immediate split rib bone grafting secondary revisions and reconstructions may be avoided. The technique and rationale are discussed. PMID- 2314509 TI - [Eurothemes. Informatics, who registers what for whom and why?]. PMID- 2314510 TI - [Clinical scientific research]. PMID- 2314511 TI - [Deglutition disorders caused by mediastinal carcinomatosis, a late sequela of breast carcinoma]. PMID- 2314512 TI - [What is the value of heart rehabilitation?]. PMID- 2314513 TI - Use of adult psychiatric services by primary care physicians in midwestern cities. AB - Primary care physicians in the tri-state area of Nebraska, Iowa and South Dakota were surveyed concerning their baseline practices in requesting psychiatric consultations, and their recommendations for improvement in psychiatric consultation. A two-page questionnaire was used to collect data. The information obtained was analyzed by tetrachoric correlations. Our results indicate that most primary care physicians refer patients to psychiatrists and prescribe psychotropic medications. It was generally noted that the respondents do not do psychotherapy themselves. In contrast to studies from other areas, our research showed that the symptoms which prompted psychiatric referral the most are psychosis and depression. Suggestions for improvement in psychiatric consultations included that psychiatrists need to be more available to the primary care practitioner. It was also indicated that financial constraints, social stigma and psychiatric shortage were problems in referral of patients to psychiatrists. PMID- 2314514 TI - Monostotic fibrous dysplasia: a rare source of hand pain. A report of a case. PMID- 2314515 TI - Metaphylaxis for calcium containing kidney stones. A reappraisal. PMID- 2314516 TI - A study of the importance of fine needle aspiration cytology in the diagnosis of the solitary thyroid nodule. AB - The results of 287 fine needle aspirations (FNAs) of the thyroid, performed between 1 January 1982 and 31 December 1986, were retrospectively analysed with respect to clinical history, physical examination, scintigraphy and echoscopy, and compared with the results of the histological examination of thyroid tissue removed from the 65 patients who were operated. Except for the follicular tumour group, FNA examination proved to be the best method for differentiating benign and malignant lesions. The specificity was found to be 48%, the sensitivity 86%. The only value of scintigraphy and echoscopy appears to be in their supporting role. Based on these results a new strategy for the evaluation of thyroid nodules is proposed, in which the FNA examination has a more important place in the diagnosis than before. PMID- 2314517 TI - Continuous intravenous administration of daunorubicin and cytarabine for remission induction of poor risk acute myelogenous leukaemias and myelodysplastic syndromes. AB - Seventeen consecutively admitted poor risk acute myeloid leukaemia (AML) patients and 4 patients with myelodysplastic syndrome (MDS) were treated with a remission induction regimen consisting of a 7-day continuous intravenous infusion of conventional doses of cytarabine and of three 24-h constant rate infusions of daunorubicin administered intermittently on days 1, 3 and 5. The diagnoses were: relapsed primary AML in 6 patients, secondary AML in 11 patients (9 untreated, 2 relapsed) and MDS in 4 patients. The median age was 50 yr. Five of 6 patients with relapsed primary AML, 3 of 11 patients with secondary AML and 2 of 4 patients with MDS achieved complete remission (CR). The overall CR rate was 48% with a median remission duration of 5 months (range: 0.25-20 months). Few acute toxic side effects were observed thanks to the constant rate of infusion of daunorubicin. PMID- 2314518 TI - The straight back syndrome. AB - Chest wall deformities may produce signs that closely mimic organic heart disease. In this category, the straight back syndrome is well recognized. Although clinical identification of this syndrome is thought sufficient to withdraw from any further investigation, its association with idiopathic mitral valve prolapse--a cardiac lesion with considerable morbidity and mortality--may be underestimated. The literature on straight back syndrome is reviewed and its association with mitral valve prolapse discussed. PMID- 2314519 TI - Mitoxantrone, methotrexate and chlorambucil in metastatic breast cancer, a combination with relatively low subjective toxicity. AB - Thirty-three patients with metastatic breast cancer received 135 cycles of chemotherapy consisting of mitoxantrone, methotrexate and chlorambucil. Forty eight per cent of the patients achieved a partial response, and the median response duration was 8 months. Patchy alopecia was seen in 10 patients, but only 2 required a wig. In approximately half of the cycles, there were no complaints of nausea or vomiting. Nausea only was recorded in 27% of the cycles; nausea and vomiting in 26%. This combination regimen is active with a low degree of subjective toxicity. PMID- 2314520 TI - Campylobacter jejuni: clinical and diagnostic value of serum antibody titres. AB - Eighty patients with either bacteriologically confirmed Campylobacter jejuni infection and/or an antibody titre value of at least 1:80, determined by ELISA, were studied. A significant correlation was found between titre value and severity of symptoms (P = 0.015). Although a correlation was noted between symptoms score and endoscopic abnormalities, this was not quite statistically significant (P = 0.053). Comparison of patients with a titre of at least 1:1280 and those with lower titre values revealed a significantly higher symptom score (P = 0.019) and endoscopic score (P = 0.015) in patients with a higher antibody level. By using the previously recommended titre of 1:640 as a cut-off point for active infection, all significant differences were lost. Of 12 patients with positive stool culture, 7 had a titre value of at least 1:1280, suggesting a sensitivity of 58%. However, of 20 patients with negative culture, 4 showed this titre value, three of whom were studied several weeks after the onset of their illness. In those patients with clinically proven Campylobacter infection, the antibody response was characterized by a rapid initial rise and a slow four-fold drop in antibody titre after 3 to 5 months. Colonic involvement of the infection was seen in 63% of our patients with positive cultures. Our results support the conclusion that ELISA is a valuable method of diagnosing C. jejuni infections when stool cultures are likely to become negative, as is the case in prolonged complaints or complications after gastro-enteritis or in proctocolitis or after the use of antibiotics. Serial serum samples have no advantage over a single sample for antibody detection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314521 TI - Orthostatic hypotension caused by sympathectomies performed for hyperhidrosis. AB - We studied sympathetic cardiovascular control in a patient after sympathectomies and found severe hypoadrenergic orthostatic hypotension before and after, but not during upright exercise. This report is the first to correlate in man anatomical sympathetic lesions with autonomic function test results and to document that in a sequence of sympathectomies orthostatic hypotension does not develop until the major part of splanchnic sympathetic outflow is destroyed. PMID- 2314522 TI - Hypokalaemia and lactic acidosis in a patient with myelomonocytic leukemia. AB - We report a patient with myelomonocytic leukaemia, persistent hypokalaemia and lactic acidosis. Cytotoxic chemotherapy induced a short remission with normalisation of the potassium concentration; death resulted from lactic acidosis. These two uncommon complications of leukaemia are discussed briefly. PMID- 2314523 TI - Combined therapy in the treatment of gastric epithelioid leiomyosarcoma. AB - In recent years it has been reported that the chemotherapeutic CYVADIC regime has contributed well to the treatment of advanced soft tissue sarcomas. We treated a patient with a large gastric epithelioid leiomyosarcoma with a combination of surgery and the CYVADIC regime. We believe that our result warrants further investigation in this field. PMID- 2314524 TI - Computerized medical information system enhances quality assurance. A 10-year experience in chronic maintenance hemodialysis patients. PMID- 2314525 TI - Erythropoietin and anemia in the progression of Balkan endemic nephropathy and other renal diseases. AB - We have investigated anemia in patients at different stages of the evolution of three chronic renal diseases: Balkan endemic nephropathy (BEN), chronic pyelonephritis (PN) and chronic glomerulonephritis (GN). A total of 88 patients with creatinine clearances from 9 to 118 ml/min and hemoglobin concentrations from 70 to 160 g/l were studied with regard to the relationship, if any, between erythropoietin production and the type and stage of nephropathy. Anemia in BEN was a particular focus of interest since it had been stated that in BEN, anemia precedes renal failure. Our data neither prove nor disprove this statement. A significant positive correlation between creatinine clearance and hemoglobin concentration was found in all three nephropathies, indicating that in the patients studied the severity of anemia increased with the impairment of renal function regardless of the underlying disease. Serum levels of immunoreactive erythropoietin were in the normal range in 54 patients, moderately increased in 20 and slightly decreased in 14. The erythropoietin level appears to be unrelated to the stage of renal failure or the type of nephropathy. The only exception was the subgroup where the patients with glomerulonephritis and normal renal function had increased serum erythropoietin levels and significantly higher parameters of red blood cell concentration than the patients from the same subgroup with tubulointerstitial nephropathies. In patients with severe renal failure and anemia, serum erythropoietin levels were inappropriately low for the degree of anemia, indicating that erythropoietin plays a role in the pathogenesis of the anemia. PMID- 2314526 TI - Superiority of the internal jugular over the subclavian access for temporary dialysis. AB - We studied angiographically the access route 1-27 months after the insertion temporary dialysis catheters in 52 patients: 32 subclavian and 20 internal jugular. The two groups were statistically similar with respect to age, sex and race. The subclavian catheters were left in for a mean of 11.5 days (2-22) while the internal jugular ones were inserted for 15.8 days (5-25; p = 0.0015). One hundred percent of the internal jugular patients were free of any venogram abnormalities in their venous access return. In marked contrast, 50% of the subclavian sites had mild to severe stricutures with 90% having 70-100% occlusion of the subclavian vein. Six patients had bilateral severe strictures. The long term stricture rate of subclavian catheters in the subclavian vein was unacceptably high compared to the internal jugular route. PMID- 2314527 TI - Influence of fluid removal during haemodialysis on macro- and skin microcirculation. Haemodynamic pathophysiologic study of fluid removal during haemodialysis. AB - Changes of macro- and microcirculation during haemodialysis and fluid removal are probably dependent on ultimate fluid status and on the efficacy of various regulation mechanisms, especially the catecholamines. This was studied in 20 chronic dialysis patients. Pre- and postdialysis stroke volume, mean arterial pressure, heart rate and systemic vascular resistance were measured. Furthermore, microcirculation was studied by Laser Doppler flow and by intravital microscopy of finger nail fold, measuring red blood cell velocity and capillary density. Pre and postdialysis noradrenaline and adrenaline were measured. Nine patients proved to be hypovolaemic after dialysis (group I) and 11 patients proved to be normovolaemic or less hypervolaemic (group II) according to vena cava inferior parameters. There was a significant decrease of mean arterial pressure and stroke volume in group I, and an increase of heart rate, whereas in group II there was only a decrease of mean arterial pressure. Systemic vascular resistance did not change in both groups. Noradrenaline decreased although not significantly in both groups, whereas in group I adrenaline increased significantly. There was a significant decrease of skin perfusion in group I, whereas in group II there was a significant increase. Capillary density increased significantly in group II after reaching normovolaemia. Underhydration was leading to a decrease of skin microcirculation on the basis of a decrease of stroke volume and an increase of adrenaline levels. In hypervolaemic patients, who were ultrafiltrated to normovolaemia, skin microcirculation improved on the basis of a decrease of arterial and venous pressure and consequently a decrease of the myogenic response as a local autoregulatory effect. PMID- 2314528 TI - Aluminum removal in uremic patients after desferrioxamine infusion: is hemofiltration more effective than hemodialysis? PMID- 2314529 TI - Is the urine anion gap a reliable index of urine ammonium excretion in most situations? PMID- 2314530 TI - Urinary oxalate excretion during intravenous infusion of diuretics in man. PMID- 2314531 TI - Erythrocyte calcium content and cell deformability in chronic renal failure. PMID- 2314532 TI - Is membranoproliferative glomerulonephritis an autoimmune disease? PMID- 2314533 TI - Usefulness of norfloxacine prophylaxis in late recurrent urinary tract infection after renal transplantation. PMID- 2314534 TI - Response to prednisone in membranous nephropathy associated with sarcoidosis. PMID- 2314535 TI - Urinary enzyme excretion after donor nephrectomy--how should we express and compare excretion rates of the remaining kidney after donor nephrectomy? PMID- 2314536 TI - Technetium-99-labelled methylene diphosphonate uptake scans in patients with dialysis arthropathy. AB - Patients on long-term haemodialysis suffer from dialysis arthropathy due to the deposition of dialysis amyloid. We investigated the use of 99Tc-labelled methylene diphosphonate bone scans in 17 patients as a possible in vivo diagnostic technique. In most clinically affected joints, with the exception of shoulders and hands, there was increased radioisotope uptake consistent with uptake by periarticular bone. In addition, we describe intense soft-tissue uptake around some clinically affected large joints. In contrast, control groups of patients on haemodialysis without arthropathy and patients without renal failure did not have increased uptake. A semi-quantitative scale of uptake was devised, and the following correlations were significant: pain perception and isotope uptake score in the ankles and feet, and the number of radiological lesions and isotope uptake scores in the wrists and knees. The following sites where the radioisotope might bind in the affected joints are proposed: amyloid deposits, areas of soft-tissue calcification, or areas of increased bone turnover. It is concluded that whereas the scanning technique cannot make a definite diagnosis of amyloid and, therefore, cannot be expected to supersede histological diagnosis, it is a useful adjuvant investigation, of particular importance in those patients unable or unwilling to undergo biopsy. PMID- 2314537 TI - Renal hemodynamic and tubular response to furosemide in man during normal and restricted sodium intake. AB - To investigate the factors determining the natriuretic response to furosemide (F) during Na restriction, we performed clearance studies in 7 healthy humans on a daily Na intake of 200 and 20 mmol. The maximum urine flow during water loading (Vmax) and simultaneous F administration was used as index of tubular fluid output from the proximal tubules. The F-induced natriuresis was only moderately reduced during Na restriction (Na excretion on low vs. normal Na intake: 4.28 +/- 0.25 vs. 4.94 +/- 0.25 mmol/min; p less than 0.05). The diminished natriuresis was mainly due to a significant fall in Na delivery to Henle's loop of 0.51 +/- 0.10 mmol/min which was either caused by a decrease in filtered Na load or a rise in fractional proximal reabsorption. Fractional distal Na reabsorption was less suppressible by F during Na restriction, but this contributed relatively little (0.15 +/- 0.11 mmol/min) to the total reduction in Na excretion (0.66 +/- 0.10 mmol/min). The F-induced increases in uric acid, phosphate, and bicarbonate excretion suggest an additional proximal site of action of F. This was confirmed by a rise in lithium clearance (CLi), another alleged index of tubular fluid delivery from the proximal tubules. However, the magnitude of the rise in CLi to values markedly exceeding Vmax suggest that CLi overestimates tubular fluid delivery to Henle's loop during F administration. PMID- 2314538 TI - Comparison of psychosocial adjustment of male nondiabetic kidney transplant and hospital hemodialysis patients. AB - Psychosocial adjustment and psychological distress was compared in 31 male nondiabetic successful renal transplant and 31 hospital hemodialysis patients, matched for duration of treatment, age, education, and family status. The only significant difference between the two groups was that the transplant patients were more satisfied with the medical staff. Vocational rehabilitation was similar in both groups. Sexual interrelationships, as reported by the patients, were slightly, but insignificantly, better in the transplanted group. Thus, the psychological adjustment of transplant and hemodialysis patients is similar when demographic differences are accounted for. PMID- 2314539 TI - Erythrocyte ferritin in patients on chronic hemodialysis treatment. AB - Serum ferritin (SF) and erythrocyte ferritin (EF) were evaluated in 35 patients on chronic hemodialysis treatment (CHD), in 45 healthy subjects and in 22 nonnephropathic females with iron deficiency anemia. Twenty-five CHD patients with basal SF less than 500 micrograms/l were treated orally with 200 mg of Fe2+ for 2 months and the positive (hemoglobin increase greater than 1 g/dl) or negative response to the therapy was correlated to the basal levels of SF and EF. Three groups of CHD patients could be defined on the basis of their basal SF levels (hypo-, normo- or hyperferritinemic). Nine patients with increased SF levels had also EF levels significantly higher than the other CHD patients and controls since they were probably iron-overloaded. In the other 2 groups of CHD patients, EF levels were significantly higher than in controls for each level of SF probably because of the reduced utilization of iron by uremic bone marrow. Among the 25 treated CHD patients, only 5 responded to the therapy: 3 were hypoferritinemic while the other 2 responders had basal SF within the normal range. Four hypoferritinemic patients did not respond to the therapy. Four out of five responders had the lowest EF levels among CHD patients. EF measurement could be an important and useful test in detecting the presence of an iron deficiency erythropoiesis in CHD patients. PMID- 2314540 TI - Serum apolipoproteins A and B, lecithin: cholesterol acyl transferase activities and urinary cholesterol levels in nephrotic syndrome patients before and during steroid treatment. AB - Serum apolipoproteins A (Apo-A) and B (Apo-B) and lecithin: cholesterol acyl transferase (LCAT) activities and 24-hour urinary cholesterol levels were estimated in 25 nephrotic children before and during steroid treatment with 4 weeks of daily prednisolone followed by another 4 weeks of alternate-day prednisolone. The patients with untreated nephrotic syndrome (NS) showed significant decrease in serum Apo-A and LCAT activities associated with significant increase in serum Apo-B and urinary cholesterol levels compared to healthy controls (n = 25). Serum Apo-A levels correlated directly and Apo-B levels inversely with the serum albumin concentrations. After a transient elevation, the serum Apo-A level returned to control range by 8 weeks of treatment accompanied by a gradual increase in serum LCAT activity and decrease in urinary cholesterol excretion. Though, the serum Apo-B level was decreased with treatment, it was still significantly high compared to the controls. PMID- 2314541 TI - Fluctuation of vasopressin secretion in chronic hypernatremia. AB - Herein we will describe a case of chronic hypernatremic-hyperosmolar syndrome with cerebral localization of systemic sarcoidosis. Several determinations of plasma arginine vasopressin (p-AVP) at various plasma sodium levels were carried out in this patient. During the study p-AVP values varied between 2.6 and 9.5 pg/ml. A high percentage of them was related to plasma osmolality, pointing out that p-AVP secretion was osmotically mediated. This behavior is in contrast with the tendency of hypernatremic patients previously reported in the literature, in whom p-AVP values were inappropriately low for the corresponding degree of plasma osmolality, suggesting that vasopressin secretion was not influenced by osmotic stimulation. Furthermore, our case, unlike those previously described, showed high values of urinary osmolality. In conclusion, our patient represents, in essence, the 'middle' of the spectrum of the hypodipsic-hypernatremic syndrome, because she is to be inserted between the majority of patients who have little or no osmotically mediated AVP release and the case of a child, recently described, who had completely normal AVP secretion. PMID- 2314542 TI - Acute renal failure due to pyelonephritis. AB - Acute renal failure developed in a 3-year-old boy with acute pyelonephritis. Renal biopsy showed acute interstitial infiltration of neutrophils and macrophages. There were also glomerulitis and capillary tuft thrombosis. He required peritoneal dialysis, but subsequently recovered renal function. Prompt antimicrobial therapy is crucial to insure a favorable outcome. Pyelonephritis is an unusual cause of acute renal failure in infants and children. PMID- 2314543 TI - The role of HLA-DR4 in the long-term prognosis of IgA nephropathy. AB - The study was performed to clarify the relationship between the long-term prognosis of IgA nephropathy and the HLA-DR4 antigen. From the 130 patients typed for HLA antigens, stable (n = 42) and progressive (n = 45) patient groups were selected. DR4 frequency was not different in the two groups (stable, 66.7 vs. progressive, 53.3%). However, the frequencies of HLA-DR4 and B35 in the 130 patients were significantly higher than those in the national control (DR4; 60.0 vs. 41.6%; B35:30.0 vs. 15.5%). We concluded that DR4 played no role in the long term prognosis of IgA nephropathy, but that B35 and DR4 were associated with the disease in the Japanese population. PMID- 2314544 TI - Acute renal failure and rhabdomyolysis following cocaine abuse. PMID- 2314545 TI - Suppression of complement activation in hemodialysis patients. PMID- 2314546 TI - Hemodialysis and cancer. PMID- 2314547 TI - Elevated serum IgE levels in children with nephrotic syndrome, a steroid resistant sign? PMID- 2314548 TI - Effect of hyperoxalaemia on factor VIII-related antigen in uremia. PMID- 2314549 TI - Nephrotic syndrome associated with recombinant interleukin-2. PMID- 2314550 TI - Scintigraphic evaluation of renal function in renal transplant donors. PMID- 2314551 TI - Progressive renal failure despite discontinuation of mefenamic acid. PMID- 2314552 TI - Horseshoe kidney and membranous glomerulonephropathy. PMID- 2314553 TI - Prediction of subsequent motor and mental retardation in newborn infants exposed to alcohol in utero by computerized EEG analysis. AB - In a prospective, blinded study 38 infants of mothers with varying quantities of alcohol ingestion during pregnancy had an EEG at 40 weeks post conceptional age. Bayley Development Tests were administered between 1.5 and 10 months of age. The total power of the EEG during REM sleep was inversely related to subsequent motor development (r = -0.51, F = 13.1, p less than 0.0008) whereas the total power of the EEG during quiet sleep was inversely related to subsequent mental development (r = 0.61, F = 24.4, p less than 0.0001). In alcohol exposed babies EEG abnormalities were present even in the absence of fetal alcohol syndrome (FAS). In 16 older children born to abstainers or alcoholic mothers similar results were obtained. Thus, the power of the EEG during REM and quiet sleep at birth appears to be a sensitive index of alcohol effects on the fetal brain and may be used to predict future motor and mental development. PMID- 2314554 TI - Dendritic development of motor neurons in the cervical anterior horn and hypoglossal nucleus of normal infants and victims of sudden infant death syndrome. AB - Morphometric Golgi methods were used to study dendritic development of neurons in the cervical ventral and dorsal horns and the hypoglossal nucleus of 8 victims of sudden infant death syndrome and 20 age-matched control infants. The dendrites and spines of these neurons proliferated rapidly until 28 weeks gestation, then increased slowly until shortly after birth. Dendritic spine density of motor neurons in the cervical anterior horn and hypoglossal nucleus of victims of sudden infant death syndrome was similar to that of the controls. Thus, the delayed maturation of dendritic spines seen in the reticular formation and vagal nuclei is not present in motor neurons of the cervical anterior horn and hypoglossal nucleus. PMID- 2314555 TI - Spinal muscular atrophy in African children. AB - Forty-five African children with SMA were seen over a period of five years. Fifteen had severe infantile form (Group 1), 19 intermediate (Group 2), 9 juvenile (Group 3) and 2 cervical type. A positive family history was obtained in only 9% of patients. The female/male ratio was 1:1.7. The age of onset was under four months in Group 1, between 5-24 months in Group 2. In 77% of Group 3 onset was between 5-24 months, 22% between 25-48 months. The lower limbs were more severely affected than upper limbs in all except the two patients with cervical SMA, proximal muscles more than distal in 82% and proximal and distal muscle were equally affected in 18%. Bulbar weakness was present in 73% and facial weakness in 80% of Group 1 patients only. Fasciculation of tongue occurred in 50% of Group 1, 42% of Group 2 and 44% of Group 3 patients. Tremor of hands was seen in none of the patients in Group 1, 58% in Group 2 and 66% in Group 3. Tendon reflexes were absent or depressed in all except one patient in Group 2 and were normal in the legs of the two patients with cervical SMA. The blood CK was elevated in 26% of patients. An ECG "tremor" was present in 26% of patients in Group 1, 68% in Group 2 and 66% in Group 3. Four patients (all in Group 1) died of pneumonia; the outcome in the others is not known.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314556 TI - Somatosensory evoked potentials in term and preterm infants in relation to postconceptional age and birth weight. AB - The effect of age on the maturation of median nerve somatosensory evoked potentials (SEPs) was studied in 103 normal neonates (24 preterm, 79 term) at the postconceptional age (PCA) of 36-48 weeks. The influence of birth weight was evaluated in 44 term neonates, aged 0-7 days, according to their gestational age (GA) stratified into three groups: A: 38-39 weeks (n = 15); B: 39.5-40.5 weeks (n = 15); C: 41-43 weeks (n = 14). The mean birth weight was not different in the three groups. For all infants the N13 latency recorded at cervical (CS2-Fz) level as well as the N19 onset and peak latency at cortical (C3'/C4'-Fz) level were measured. For these parameters and for the N13 latency divided by arm length (N13/AL) and the N19 ascending time (N19AT) the P50, P97 and P3 were calculated as a function of PCA. They were all decreasing in the 36-48 weeks period, fast before 40 weeks and slowly thereafter. The SEP values of groups, A, B and C were not different, but in each group the wave pattern of the cortical SEPs was more mature in the larger than in the smaller infants. For the groups A, B and C together birth weight (in SDS) correlated inversely with the N13/AL and the N19AT (both in SDS) (r = 0.73 and 0.52 respectively, p less than 0.001). Our data indicate that the progression of maturation of the various SEP components in the period of 36-48 PCA is non-linear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314557 TI - Moyamoya disease associated with renovascular hypertension. AB - This is a report of a case history of a child with cerebral Moyamoya disease and gradual development of systemic hypertension. Sodium depletion combined with enalapril induced renal failure. A bilateral renal artery stenosis was found. Percutaneous transluminal angioplasty was not successful and was followed by autotransplantation of both kidneys. Histopathological examination of the renal arteries revealed intimal hyperplasia. PMID- 2314558 TI - Pigmentary type of orthochromatic leukodystrophy with early onset and protracted course. AB - The pigmentary type of orthochromatic leukodystrophy (OLD) is a rare disorder in adults; only one questionable childhood case has been observed. We report the sporadic case of a male aged 26 years with early onset and protracted course. He presented retarded motor development from birth with ataxic gait and, at age 13 years, developed progressive mental and neurologic deterioration with tetraparesis, ataxia and seizures and died in a disabled, mute state. Repeated CT scans showed progressive diffuse cerebral atrophy and low density of the hemispheric white matter. Autopsy revealed OLD with pigmented macrophages and glial cells, ultrastructurally showing storage of lipofuscin and ceroid with multilamellar bodies or finger-print profiles. Abnormal cytoplasmic inclusions in reduced oligodendroglial cells suggest demyelination due to a primary defect of oligodendroglia in this rare disorder. PMID- 2314559 TI - Congenital muscular dystrophy with cerebral involvement--report of a case of "occidental type cerebromuscular dystrophy"? AB - Cerebral CT scan abnormalities have been seen to be afflicted with some cases of classic occidental type congenital muscular dystrophy (CMD) with normal or borderline intelligence without neurological abnormality. A case is presented with early hypotonia, joint contractures, muscle biopsy features of CMD, normal intelligence and diffuse white matter hyperlucency on CT scan. Every CMD case should be screened with cerebral CT and magnetic resonance (MRI) scans to reach more aspects of this heterogenous disorder. PMID- 2314560 TI - Infant feeding and cardiorespiratory maturation. AB - 134 preterm infants were investigated in their ability to coordinate sucking and breathing. Of those infants who did not coordinate, 79% showed immature cardiorespiratory control whereas of those who suck and breathe simultaneously only 12% had poor cardiorespiratory control. This finding suggests that in infants with poor coordination of sucking and breathing an investigation of cardiorespiratory control might be indicated. PMID- 2314561 TI - Visual memory lateralization in pigeons. AB - Previous experiments employing simple visual discrimination tasks have revealed a cerebral lateralization in the visual system of pigeons with a dominance of the left hemisphere. Until now, visual memory lateralization in birds has not been investigated. To study possible asymmetries of visual memory functions, a simultaneous instrumental discrimination procedure was used. The animals were trained to discriminate 100 different visual patterns from a further 625 similar stimuli. Retention tests were conducted under binocular and monocular conditions. When the subjects looked monocularly, retention performance was significantly higher with the right eye (left hemisphere) than with the left eye (right hemisphere). The results suggest that the lateralization of the pigeon's visual system depends at least partly on an asymmetry in visual memory capacity. PMID- 2314562 TI - Crossmodal short-term memory of haptic and visual information. AB - Rhesus monkeys were trained on a within-subjects design to assess whether they could perform concurrently visual-to-haptic (V-H) and haptic-to-visual (H-V) crossmodal delayed matching-to-sample (DMS). A parametric analysis was conducted of the effect of delay between presentation and re-presentation of the test discriminanda (three-dimensional geometric objects). The results indicate that (a) monkeys are capable of concurrent V-H and H-V crossmodal matching of objects by shape, size, and texture; (b) monkeys acquire faster and perform better crossmodal matching in the V-H direction than in the H-V direction; (c) as they learn to perform DMS with successive object pairs, monkeys transfer some- procedural--knowledge from the use of one pair to the use of the next; and (d) in the monkey, crossmodal short-term memory, as measured by DMS performance, has a temporal decline. PMID- 2314563 TI - The effects of developmental factors on IQ in hemiplegic children. AB - The effects of early unilateral brain lesions on subsequent intellectual functioning were explored in hemiplegic children with congenital or acquired lesions. For congenital hemiplegics who sustained damage pre- or perinatally, lower intellectual functioning (IQ) was most highly associated with longer elapsed time since lesion. Moreover, including lesion size as an additional predictor of IQ did not account for significantly more variance than elapsed time since lesion alone. In contrast, for acquired hemiplegics who sustained damage after birth, lower intellectual functioning was highly associated with larger lesion size. In this group neither elapsed time since lesion nor age at testing accounted for significantly more IQ variance than lesion size alone. Possible effects of maturational factors and functional plasticity are considered in interpreting this pattern of results. PMID- 2314564 TI - Arithmetic and laterality. AB - Relationships between arithmetic ability, hand preference and hand skill were investigated in a general population sample of schoolchildren, aged 9-11 years. Incidences of non-right-handedness were highest in the children best at arithmetic and fell progressively through average and below average groups. Strong effects were found for hand skill; level of ability declined linearly from left to right across the R-L continuum in both sexes. Strong dextrality was associated with poor left hand skill and not superior right hand skill. Arithmetic ability was positively associated with left hand skill but not with right hand skill. PMID- 2314565 TI - Within-modal and cross-modal consistency in the direction and magnitude of perceptual asymmetry. AB - Three auditory and three visual tests of PA were administered to 45 healthy dextrals in order to evaluate within-modal and cross-modal consistency in the direction and magnitude of perceptual asymmetry (PA). Thirty-three subjects were retested after a 4-8 week interval to determine reliability of individual measures and stability of inter-test relationships. Pairs of visual and auditory tests consisted of exactly the same stimuli. Within-modal and cross-modal concordance in the direction of PA was high, providing additional empirical support for existing models of the neural basis of PA. Cross-modal correlations in the magnitude of PA were near zero despite highly significant within-modal correlations. Meaningfulness of the stimuli did not affect the magnitude of PA, although the presence of an orienting expression prior to each dichotic pair did. These three observations provide new information about the neural processes that determine the magnitude of PA. PMID- 2314566 TI - Cerebral correlates of imagining colours, faces and a map--II. Negative cortical DC potentials. AB - Cortical activation patterns as measured by negative shifts of the scalp-recorded cortical steady potential ("DC shifts") were assessed in 28 normal subjects during imagining colours, faces, and a spatial map. Imaging resulted in sustained negative DC shifts at temporal, parietal and particularly at occipital sites. The topographic distributions of such DC shifts was modulated as a function of whether spatial or visual imagery was performed. During imaging the spatial map, a parietal maximum was observed, as opposed to a distribution in favour of temporal and occipital sites during imagining faces and colours. Results suggest a neuroanatomical dissociation between visual and spatial imagery. Since a similar visual-spatial dichotomy exists in perception, the finding is interpreted as further evidence of a shared cerebral substrate for images and percepts. The results are discussed in conjunction with the joint blood flow study. PMID- 2314567 TI - Subjective ordering, short-term memory, and the frontal lobes. AB - Four tasks relying on short-term retention, i.e. digit span, missing scan, randomization span, and pointing span were presented to patients with frontal lobe lesions and normal controls. Digit span was considered a measure of passive short-term memory, the other three tasks additionally reflect comparing processes, and two of these, the randomization and pointing spans, also measure active ordering by the subject. The results confirmed Petrides and Milner's (Neuropsychologia 20, 249-262, 1982) hypothesis that frontal-lobe patients are typically deficient in subject-ordered tasks. It is also suggested that they are deficient in a spontaneous generation, rather than comparison component of subjective ordering. PMID- 2314568 TI - Manual asymmetries in the reproduction of a 3-dimensional spatial location. AB - Two experiments examined differences in the reproduction of preselected arm positioning movements. In Experiment 1, subjects defined a position in right space with a right index finger, or a position in left space with the left index finger, and then attempted to reproduce the position with either the left or the right hand. Subjects were more accurate when vision was available and when the reproduction hand was the same as the criterion hand. Availability of vision reduced the same hand advantage. There were no accuracy differences between the left and right hands. Experiment 2 was designed to determine whether the left left and right-right criterion and reproduction advantages evident in the no vision condition of the first experiment were accounted for by the two movements being made by the same hand or by being performed in the same space. The results demonstrated that accuracy depended primarily on whether movements were made with the same hand. No right/left hand advantage was observed. The absence of a right hand advantage in either experiment may be due to the spatial complexity of the task examined or to the relative absence of any temporal constraints. PMID- 2314569 TI - Supraspan learning in patients with unilateral anterior temporal lobe resections. AB - The present data addresses the role of the anterior temporal lobe in verbal and visual supraspan learning. Patient subjects had either a left or right standardized temporal lobe resection, which involved extensive removal of mesial temporal lobe structures. Neither patient group showed marked deficits on either the verbal or visual supraspan learning tasks, although an unexpected performance variation occurred. A tendency to mild depression of performance on the verbal supraspan learning task was observed among right temporal-lobectomy patients. Nevertheless, the overall results indicate that anterior temporal lobe structures are not independently critical for supraspan learning. These findings are consistent with a previous report that posterior brain regions are involved in mediating such tasks. PMID- 2314570 TI - Covert orientation of visual attention in Parkinson's disease: an impairment in the maintenance of attention. AB - Covert orientation of attention was studied in a group of patients with idiopathic Parkinson's disease and compared to a matched control group using a cued reaction time task which measured disengagement, covert movement and engagement of attention. Parkinson patients had an increased response latency and disengaged from attended locations more readily than controls. This impairment in the maintenance of attention in Parkinson's disease was comparable to that produced in a previous study by pharmacological blockade of brain catecholamines in normal subjects. It is suggested that an impairment in the maintenance of oriented attention may underlie some of the cognitive deficits reported in Parkinson's disease. PMID- 2314571 TI - Frontal hypermetabolism and thalamic hypometabolism in a patient with abnormal orienting and retrosplenial amnesia. AB - A patient with verbal amnesia and a propensity to direct his attention to the right following a retrosplenial area lesion was studied with positron emission tomography using [F-18] fluorodeoxyglucose. These studies showed that the left thalamus was hypometabolic, and the anterior 2/3 of the left hemisphere was hypermetabolic when compared with the right. There were no significant differences seen in the medial temporal lobes. Based on this study, it is posited that interruption of hippocampal input into the anterior thalamus was responsible for the amnesia, and the left frontal hyperactivity was associated with the propensity to attend contralaterally. PMID- 2314572 TI - Characteristics of the memory loss of a patient with Wernicke-Korsakoff's syndrome without alcoholism. AB - The memory loss in alcoholic Wernicke-Korsakoff syndrome has been well characterized. However, it has been suggested that some of the neuropsychological defects seen in these patients are due to frontal lobe dysfunction resulting from chronic alcohol abuse. The present report details the nature and extent of the amnesia in a Wernicke-Korsakoff patient who did not have a history of alcoholism. In spite of her normal performance on measures of frontal lobe function, this patient showed many characteristics similar to those seen in alcoholic Wernicke Korsakoff syndrome including a graded loss of remote memories and abnormal semantic information processing. Thus, the extent of the "core" features of this amnesic syndrome may be greater than was previously thought. PMID- 2314573 TI - Directed attention dichotic listening in reading disabled children: a test of four models of maladaptive lateralization. AB - In two experiments, critical a priori tests compared four competing LD theories of maladaptive language lateralization (Poor Structural Lateralization; Excessive RH Activation; Excessive LH Activation; Excessive LH or RH Activation). In Experiment 1, 32 auditory-linguistic LD children from public schools were compared to 32 high-achieving, age-matched controls. Experiment 2 replicated the main findings of Experiment 1 by comparing 14 LD children to 14 controls attending a private school. The effect of priming or ear order was analyzed in a directed attention, dichotic paradigm with strings of quadruple digit names as stimuli. The order in which the ears were monitored (LE first or RE first) determined (1) in both experiments whether the LD children compared to controls were more weakly or strongly lateralized and (2) in Experiment 2 whether the REA correlated negatively of positively with reading and spelling achievement. The results indicate that the hemispheric processes involved in disengaging and shifting response strategies between dichotic channels may share common neuronal mechanisms with cognitive processes that are important to school achievement. Rather than LD children suffering from a fixed laterality deficit, the results are consistent with the view that a task-dependent attentional dysfunction may interfere with left hemisphere language processes by overengaging either hemisphere. However, pronounced asymmetry in the relative magnitude of the effects at each channel also suggests greater interference in LD children between the systems controlling auditory-linguistic attention and lateral orienting. PMID- 2314574 TI - Lateralization for the expression and perception of facial emotion as a function of age. AB - In order to test the hypothesis of right hemisphere changes with age, this study examined lateralization for facial emotion in young, middle-aged, and older women (N = 90). For expression, subjects were photographed while posing positive and negative emotions. Composite photographs were created and rated for intensity. For perception, subjects were required to make intensity judgements about emotional chimeric faces. Overall, subjects demonstrated significant left-sided facial asymmetry for expression and significant left hemispace biases for perception. The findings for facial expression were not influenced by emotional valence or resting face asymmetries. There were no changes in lateralization as a function of age for either expression or perception. Taken together, these findings lend support to the notion that the right hemisphere mediates emotional processing across the adult life span. PMID- 2314575 TI - Enhanced right hemisphere involvement during cognitive processing may relate to intellectual precocity. AB - In the present study, intellectually precocious and average ability youths performed a dichotic listening task (Experiment 1) and a free-vision chimeric face task (Experiment 2). Patterns of hemispheric lateralization and the relative involvement of the left and right hemispheres during cognitive processing were assessed. In Experiment 1, the average ability youths demonstrated a right ear/left hemisphere (re/LH) superiority for identification of CV syllables, while the gifted subjects failed to show any ear/hemisphere advantage. In Experiment 2, members of both groups tended to judge the leftside smile/rightside neutral half faces as "happier", a pattern indicative of enhanced right hemisphere (RH) arousal. Notably, the degree of RH involvement was significantly greater in the gifted as compared to average ability youths. Moreover, laterality scores of the precocious on the chimeric face task correlated with their performance on the College Board Scholastic Aptitude test (SAT), i.e. the greater the leftward bias, the higher the SAT score. These findings, taken in composite, suggest that a high level of RH involvement during cognitive processing may be related to intellectual precocity. PMID- 2314576 TI - Digit span and visual neglect: a puzzling relationship. AB - Weinberg et al. found a relationship between the presence of extinction and the discrepancy between backward and forward digit span among left hemiplegic patients. The present study replicates this finding in a group of 37 patients suffering from unilateral left visual neglect, demonstrating a strong relationship between degree of neglect and digit span discrepancy. A principal components analysis of a neurospychological examination revealed three main independent components--Neglect, Verbal Memory and Non-verbal Memory respectively. Digit Span Discrepancy had one of the highest loadings on the neglect factor, and loaded significantly on no other factor. Multiple regression analysis showed that the relationship of Digit Span Discrepancy with Degree of Neglect exists independently of visuo-spatial ability, and this is also true for paced auditory serial addition (PASAT) scores for one of the two main indices of neglect. The implications of this for understanding neglect are discussed. PMID- 2314577 TI - Association between left-handedness and allergy: a reappraisal. AB - There are conflicting reports in the literature about the possible association between left-handedness and immune disorders, including autoimmune diseases as well as allergies. In this study we compared the distribution of right- and left handers, assessed with the Edinburgh Handedness Inventory, in a group of patients consulting an allergy clinic and a control population with a similar sex and age distribution. There was no overall association between left-handedness and allergies, although we found a tendency towards left-handedness in patients whose allergic symptoms started before puberty, suggesting that left-handers may have an increased predisposition to allergic disease that manifests itself during early life. PMID- 2314578 TI - Comparative cognitive effects of anticonvulsants. AB - We investigated the neuropsychological effects of carbamazepine, phenobarbital, and phenytoin in 15 partial complex epilepsy patients treated with each drug for 3 months, using a randomized double-blind, triple crossover design. Neuropsychological evaluation at the end of each treatment period included Digit Span, Selective Reminding Test, Digit Symbol, Finger Tapping, Grooved Pegboard, Choice Reaction Time, P3 evoked potential, and Profile of Mood States. Employing anticonvulsant blood levels and seizure frequencies as covariates, the only significant difference was for Digit Symbol. Performance with phenobarbital was significantly worse than with the other 2 anticonvulsants despite phenobarbital's having had the lowest overall blood levels. Our data show that patients receiving carbamazepine, phenobarbital, and phenytoin have comparable neuropsychological performance on most measures. The results suggest that the differential cognitive effects of anticonvulsants may be subtle. PMID- 2314579 TI - Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity. AB - We evaluated age at onset and lifetime risk for Alzheimer's disease (AD) in 70 kindreds with familial AD (designated FAD) composed of 541 affected and 1,066 unaffected offspring of demented parents who were identified retrospectively. Using a survival analysis method which takes into account affected persons with unknown onset ages and unaffected persons with unknown censoring ages, we found lifetime risk of AD among at-risk offspring by age 87 to be 64%. Analysis of age at onset among kindreds showed evidence for a bimodal distribution: in this sample, families with a mean onset age of less than 58 years were designated as having early-onset, while late-onset families had a mean onset age greater than 58 years. At-risk offspring in early-onset families had an estimated lifetime risk for dementia of 53%, which is significantly less than the risk of 86% that was estimated for offspring in late-onset families. Men and women in early-onset families had equivalent risk of dementia. In late-onset families, the risk to female offspring was somewhat higher than to male offspring but this difference was marginally significant. Lifetime risk of dementia in early-onset FAD kindreds is consistent with an autosomal dominant inheritance model. Our results may suggest that late-onset FAD has at least 2 etiologies; AD in some families may be transmitted as a dominant trait, whereas a proportion of cases in these and other late-onset families may be caused by other genetic or shared environmental factors. PMID- 2314580 TI - Changes in seizure activity following anticonvulsant drug withdrawal. AB - We retrospectively studied the effects of changing antiepileptic drug levels on patterns of seizure discharge in 8 patients investigated with intracerebral electrodes during presurgical evaluation. We compared seizures recorded at high levels of medication to seizures recorded at low levels for changes in seizure duration, duration from unilateral onset to contralateral spread, inter- and intrahemispheric coherence, and morphology of EEG discharges. Seizures were more frequent with low medication, as was secondary generalization. Reduction in medication did not affect the morphology of discharges at onset, duration to contralateral spread, and coherence between EEG discharges. Seizures of similar type (eg, complex partial seizures without secondary generalization) were not longer with low than with high medication. Whereas medication clearly affects seizure frequency and generalization, it has little effect on the pattern of early parts of seizures. In particular, we found no evidence that seizure discharges become bilateral or generalized more quickly when medication is reduced. PMID- 2314581 TI - Anterior temporal lobectomy for complex partial seizures: evaluation, results, and long-term follow-up in 100 cases. AB - We report evaluation and results in 100 patients who had undergone anterior temporal lobectomy for intractable complex partial seizures. Average follow-up was 9.0 years (range, 2 to 21 years). In the 2nd postoperative year, 63% were seizure free, 16% were significantly improved, and 21% were considered not significantly improved. Mean number of seizures in the last group was 27% of preoperative levels. Surgical results did not change significantly in subsequent postoperative years; good outcomes tended to persist over the longer term. We also examined the utility of continuous depth electrode monitoring in the evaluation of patients with independent bitemporal interictal epileptiform activity. Despite limited numbers of subjects in this category, there was a trend toward improved surgical outcome when such subjects were evaluated with depth electrodes. PMID- 2314582 TI - Progressive aphasia: a precursor of global dementia? AB - We studied 8 subjects longitudinally in whom isolated language dysfunction had developed gradually at a mean age of 62.8 years. The language deficits initially displayed by the subjects were characteristic of the syndrome of "progressive aphasia without dementia." By 5 years after onset of progressive aphasia, however, 7 of the 8 subjects additionally had developed mild dementia as diagnosed by clinical means, and the remaining subject demonstrated declining performance in both verbal and nonverbal psychometric measures. Thus, generalized cognitive impairment occurred in all. Neuropathologic evidence of a diffuse dementing disorder was present in the 2 subjects studied postmortem. One had Alzheimer's disease with disproportionate involvement of the left inferior parietal cortex, and the other displayed widespread neocortical neuronal loss and microvacuolation in the absence of specific histopathologic markers. In this series, progressive aphasia was a precursor of global dementia. PMID- 2314583 TI - Measles virus polypeptide-specific antibody profile in multiple sclerosis. AB - Elevated antibody (Ab) titers to measles virus (MV) is a frequent finding in MS. Although MV-Abs are synthesized intrathecally, it is not known whether this is due to polyclonal activation of B cells recruited from the blood, recognition of MV antigens within the CNS, or cross-reactivity with myelin antigens. This study examined these possibilities using purified MV polypeptides. We examined Ab reactivity to each polypeptide in serum and CSF from 21 MS patients, 5 with subacute sclerosing panencephalitis (SSPE), and 11 patients with other neurologic diseases (OND), and serum from 5 patients with acute MV infection and 11 normal controls. The serum of all subjects tested contained reactivity with MV and the 5 polypeptides. Of 21 MS patients, 20 had CSF reactivity with MV compared with 3/11 ONDs and 5/5 SSPE patients. Intrathecal MV-Ab synthesis was present in 11/21 MS patients, 5/5 SSPE, and in none of the ONDs. Nine of 21 MS patients had intrathecal synthesis of Ab to 2 MV polypeptides. Serum and CSF reactivity in MS patients was skewed towards the F polypeptide. The results are consistent with the concept of polyclonal B cell activation within the CNS, but the heightened response to F could also reflect cross-reactivity with a relevant antigen in MS. PMID- 2314584 TI - Leptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast enhanced CT of the brain. AB - We evaluated 14 consecutive patients with leptomeningeal metastasis prospectively, using both T1-weighted (T1W) gadolinium-DTPA-enhanced MR (Gd-MR) and contrast-enhanced CT (CE-CT). Thirteen had positive CSF cytology; the remaining patient had an atypical CSF lymphocytosis and primary CNS lymphoma. The patients (8M/6F) ranged in age from 8 to 70 years (median, 42 years). Tumor histology included 3 systemic and 2 primary CNS lymphomas, 3 breast carcinomas, 2 leukemias, 1 malignant schwannoma, 1 small cell lung cancer, 1 prostate cancer, and 1 melanoma. Both imaging methods demonstrated parenchymal volume loss equally well in all patients. Gd-MR revealed abnormal enhancement of meninges or parenchyma in 10 patients, including all 5 patients with positive CE-CT. Neither technique revealed any foci of abnormal enhancement in 4 patients. Gd-MR was superior to CE-CT in demonstrating and quantifying enhancing subarachnoid and parenchymal nodules in 6 patients and in demonstrating sulcal, dural, cisternal, tentorial, and ependymal enhancement. Our findings indicate that T1W Gd-MR is the preferred imaging modality in leptomeningeal metastasis and suggest that CE-CT is unnecessary. PMID- 2314585 TI - Complex visual disturbances in Alzheimer's disease. AB - Although Alzheimer's disease (AD) involves visual association cortex, previous studies have not systematically investigated complex visual disturbances in AD. We examined 30 community-based AD patients, 13 (43%) of whom had complex visual complaints, and compared them with 30 controls on 7 types of complex visual tasks. Despite preserved visual acuity and color recognition, the AD patients were impaired in the visual evaluation of common objects, famous faces, spatial locations, and complex figures. In the AD patients, we found that all 30 had disturbances in figure-ground analysis; 17 (57%) had difficulties visually recognizing actual objects ("agnosia"); those with worse dementia disability had the most complex visual disturbances; and a subgroup (6) with Balint's syndrome performed the most poorly on the complex visual tasks. This study demonstrates that a range of complex visual disturbances are common in AD and suggests that they may result from the known neuropathology in the visual association cortex. PMID- 2314586 TI - Spontaneous visual phenomena with visual loss: 104 patients with lesions of retinal and neural afferent pathways. AB - Fifty-seven percent of 104 consecutive patients with retinal or neural visual loss reported spontaneous visual phenomena (SVP). Elementary SVP occurred more commonly (51% of patients) than complex SVP (21%). SVP occur with lesions of any portion of the visual pathways. Unlike irritative hallucinations, they do not aid in localization of the lesion. SVP occur significantly more frequently with visual acuity of 20/50 or less in both eyes. These purely visual hallucinations are unlikely to herald psychiatric disease and may be release phenomena stemming from loss of inhibitory visual input. PMID- 2314587 TI - Simultanagnosia: a defect of sustained attention yields insights on visual information processing. AB - Simultanagnosia, in which subjects report a piecemeal visual experience, offers an important probe of human attention. We studied 2 subjects with simultanagnosia following bilateral superior occipital strokes. Compared with controls, they could orient attention to spatial targets in visual, auditory, and mixed-modal conditions. A different task required immediate response to the appearance or disappearance at unpredictable intervals of any element in a random-dot CRT display. The subject tested could detect less than 50% of 1,600 events, and had increased "mirages" and prolonged reaction times. Undetected events occurred anywhere and formed temporal clusters. Application of signal-detection theory confirmed abnormal sensitivity and response bias (d' and beta). Yet performance improved when a valid cue introduced events in the random display. Our results suggest that simultanagnosia was related to an inability to sustain visuospatial attention across an array, corresponding to processing failure at a level of long range (global) spatiotemporal interactions among converging inputs from early vision. The operations for orienting and sustaining attention may be dissociable at visual association cortex levels. PMID- 2314588 TI - Pharmacokinetics and safety of a phenytoin prodrug given i.v. or i.m. in patients. AB - ACC-9653, a prodrug of phenytoin synthesized to be water soluble, is converted to phenytoin by phosphatases. In this study, 43 patients received ACC-9653 IV or IM. Side effects were transient and minor. The conversion half-lives of ACC-9653 after intravenous and intramuscular administration averaged 8.4 and 32.7 minutes, respectively. Peak phenytoin concentrations occurred 42 minutes after IV and 151 minutes after IM administration. PMID- 2314589 TI - Anticardiolipin antibodies in Sneddon's syndrome. AB - We studied 24 patients (18 women, 6 men), aged 29 to 54, with Sneddon's syndrome. The clinical picture of Sneddon's syndrome was characterized by cerebrovascular disorders, livedo reticularis, disturbance of peripheral circulation, arterial hypertension, cardiac pathology (ischemic heart disease, heart murmurs), complicated obstetric history in women, and disturbed sexual function in men. In 6 of 17 examined patients with Sneddon's syndrome there was a high concentration of anticardiolipin antibodies (ACA) but no antibodies to native DNA and LE cells. The course of the disease in the patients with a high ACA level, when compared with normal ACA level patients, was characterized by a more rapid progression and more severe clinical manifestations. The study demonstrates the similarity of clinical symptoms and immunologic disturbances in Sneddon's syndrome and the antiphospholipid syndrome and suggests the importance of ACA in the pathogenesis of some cases of Sneddon's syndrome. PMID- 2314590 TI - Circadian fluctuations of contrast sensitivity in Parkinson's disease. AB - Spontaneous circadian fluctuations of motor symptoms in Parkinson's disease (PD) often occur, with dysfunction typically less severe in the early morning than in the afternoon. In 23 PD patients with or without a history of circadian motor fluctuations, we studied contrast sensitivity (CS), a non-motor function, considered to be dependent on dopaminergic transmission to see if it exhibits similar circadian variability. We tested CS throughout the day at 2-hour intervals beginning at 8:30 AM. To facilitate multiple testing sessions, we used a rapid, printed, forced choice test of CS not requiring a motor response. We tested CS in 43 eyes in the PD patients and 23 eyes in 12 controls at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles per degree (cpd). At 8:30 AM, CS in PD did not differ from that of controls, but at all other testing times it was significantly worse at 3 or more spatial frequencies. In PD, CS was significantly worse at 2:30 PM than at 8:30 AM at 3 and 6 cpd, but in controls it was unchanged throughout the day. Separate analysis of CS in PD patients, with and without a history of circadian change in motor symptoms, revealed no significant difference between the groups. These results suggest that in PD a non-motor dopaminergic function can exhibit circadian variability and that this pattern can exist in the absence of similar variability in motor symptoms. Circadian variability which parallels the most common pattern of motor variability in PD supports the notion that the CS abnormality in this condition is related to dopamine deficiency. PMID- 2314591 TI - Central lesions in chronic inflammatory demyelinating polyneuropathy: an MRI study. AB - To determine the frequency of the possible association between chronic inflammatory demyelinating polyneuropathy (CIDP) and MS, we did magnetic resonance imaging (MRI) of the brain in 19 patients with CIDP. Only 1 patient had clinical signs suggestive of central involvement. Seven of the 19 scans showed 2 or more brain "lesions." In 1 case the cause was an infarct and in 5 cases the patients were over 55 years of age and the lesions were not typical of MS. One 38 year-old patient had 2 small subcortical lesions. Typical MS lesions on MRI are uncommon in CIDP. PMID- 2314592 TI - Juvenile multiple sclerosis-like episodes associated with a defect of mitochondrial beta oxidation. AB - We describe a young girl who presented with recurrent episodes of central nervous system (CNS) demyelination mimicking multiple sclerosis. Metabolic evaluations and decreased oxidation of [9,10(n)-3H] palmitate demonstrated defective mitochondrial beta oxidation, but complementation studies of the patient's cells, fused with cell lines with known defects of beta oxidation, failed to identify a known disorder. While progressive CNS demyelination has occurred in patients with defective peroxisomal very long-chain fatty acid oxidation, this is the 1st time it has occurred with defective mitochondrial beta oxidation. This patient appears to represent a novel disorder of beta oxidation producing intermittent demyelination with profound CNS symptoms. Recognition of the defect led to appropriate therapy, which caused marked clinical improvement. PMID- 2314593 TI - Successful treatment of acquired pendular elliptical nystagmus in multiple sclerosis with isoniazid and base-out prisms. AB - We treated 3 multiple sclerosis patients who had pendular nystagmus with isoniazid (800 to 1,000 mg/d). Isoniazid abolished the nystagmus and relieved oscillopsia in 2 patients but was ineffective in the 3rd in whom the nystagmus was damped with convergence and vision improved with converging (base-out) prisms. PMID- 2314594 TI - Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes. AB - A 7-month-old boy died in a demented state after a clinical history characterized by generalized seizures, psychomotor deterioration, and fumaric aciduria. We found a marked deficiency of both mitochondrial and cytosolic fumarases in skeletal muscle, brain, cerebellum, heart, kidney, liver, and cultured fibroblasts. Fumarase activities were 30 to 50% compared with controls in both mitochondria and cytosol from cultured fibroblasts of the parents. Antifumarase cross-reacting material was present in negligible amounts in the patient's tissues. Our data indicate that this disease is an autosomal recessive encephalopathy, due to a single mutation affecting the gene encoding both forms of the enzyme. PMID- 2314595 TI - Cerebrospinal fluid production is reduced in healthy aging. AB - In order to study age-related differences in cerebrospinal fluid (CSF) production in humans, we measured the rate of CSF production in 7 young (age 21 to 36 years) and 7 elderly (age 67 to 84 years) healthy volunteers, using a modified Masserman method. In addition, we evaluated CSF protein gradients by collecting CSF in serial fractions up to the 30th ml and assaying for total protein concentration. The mean rate of CSF production was significantly less in the elderly than in the young subjects. Mean CSF total protein concentrations were higher in the elderly than in the young, and significant rostrocaudal protein gradients with similar slopes were present in both groups. However, there was no correlation between CSF production and CSF total protein concentrations or protein gradient slopes. Age related reductions in CSF production, together with the ventricular dilatation that occurs with aging, should presumably result in reduced CSF turnover and therefore influence measured concentrations of lumbar CSF constituents. PMID- 2314596 TI - Nifedipine for intractable hiccups. AB - Seven patients with intractable hiccups were treated with a calcium channel blocker, nifedipine. A daily dose of 30 to 60 mg of this drug stopped hiccups in 4 patients and improved them in a 5th patient. In 2 patients hiccups recurred within 24 hours after stopping nifedipine. Nifedipine can be effective against intractable hiccups in some patients. PMID- 2314597 TI - White matter dementia in chronic toluene abuse. AB - We studied 14 chronic toluene abusers with a comprehensive neuropsychological evaluation and cerebral magnetic resonance imaging (MRI). There were 10 men and 4 women, and the mean age was 29 years. Using a blinded global assessment of neuropsychological functioning, we found 3 patients to be normal, 3 in a borderline range, and 8 impaired. Independent analyses of white matter changes on MRI disclosed that the degree of white matter abnormality was strongly correlated (p less than 0.01) with neuropsychological impairment. Dementia in toluene abuse appears to be related to severity of cerebral white matter involvement. PMID- 2314598 TI - Human immunodeficiency virus wasting syndrome may represent a treatable myopathy. AB - We evaluated 5 patients with the diagnosis of HIV wasting syndrome. None had severe diarrhea or other causes for malabsorption. All had myopathy by clinical, laboratory, and muscle biopsy criteria. Withdrawal of azidothymidine in 3 patients did not lead to improvement. Corticosteroid therapy was effective in 3 patients. PMID- 2314599 TI - Congenital absence of the corticospinal fibers: pathologic and clinical observations. AB - We describe 2 patients with primary absence of corticospinal tracts. Both presented with delayed motor development, head lag, and spasticity of the limbs. We could not identify precentral cortex, and there were no corticospinal fibers below the internal capsules. We postulate that the fibers were displaced or interrupted early in their development. PMID- 2314600 TI - Neurosyphilis in AIDS patients: initial CSF VDRL may be negative. AB - We report 2 HIV-seropositive patients with neurosyphilis whose initial CSF VDRL tests were negative. The CSF VDRL became positive after 12 days of IV penicillin treatment for syphilitic meningitis in the 1st patient. The 2nd patient developed syphilitic polyradiculopathy and a positive CSF VDRL 3 months after treatment with IV penicillin. Serial CSF VDRL determinations may be required in AIDS patients when a diagnosis of neurosyphilis is suspected. PMID- 2314601 TI - Dextromethorphan for treatment of complex partial seizures. AB - We performed a double-blind, crossover, add-on study of the antitussive agent dextromethorphan (DM 120 mg/d) as therapy for seizures on 9 patients suffering from severe complex partial seizures. DM had no significant influence on key laboratory values, nor on anticonvulsant drug levels. Side effects were negligible. Complex partial seizure frequency increased 25% during the DM arm of the study, although this increase was not clinically significant. PMID- 2314602 TI - Periodic saccadic oscillations and tinnitus. AB - A man with essential hypertension developed stereotyped cycles of oscillopsia and bilateral "sparking" tinnitus. Eye movement recordings showed cycles of disconjugate opsoclonus, square-wave jerks, and saccadic dynamic overshoot disrupting stable fixation. Neuroimaging studies were normal. We postulate a lesion episodically disturbing saccade-related neurons and central auditory neurons in the pons. PMID- 2314603 TI - Kearns-Sayre syndrome and dilated cardiomyopathy. PMID- 2314604 TI - Superior oblique palsy due to a midbrain vascular malformation. PMID- 2314605 TI - Bilateral infarction of the medullary pyramids. PMID- 2314606 TI - A syndrome of hyperhidrosis, hypothermia, and bradycardia possibly due to central monoaminergic dysfunction. PMID- 2314607 TI - MPTP-induced up-regulation. PMID- 2314608 TI - MS referendum. PMID- 2314609 TI - Neurocysticercosis. PMID- 2314610 TI - [Comparison of MR and CT in a radiological study of Cushing's syndrome. A report on 16 cases]. AB - In 16 patients with high cortisol plasma levels MRI and CT investigation of adrenal gland region was performed; 13 also had the pituitary region examined. CT and MRI results in Cushing's Syndrome due to adrenal glands etiology (8 cases) are overlapping. The morphological criteria utilized consist in the radiological finding of bilateral adrenal hyperplasia or adrenal mass (adenoma, carcinoma). The great amount of retroperitoneal fat increases the normal contrast with both techniques. In the pituitary Cushing's Syndrome MRI was more sensible than CT as far as it concerns ACTH producing pituitary lesion assessment; this technique may show 5 mm diameter adenomas for their high signal intensity. PMID- 2314611 TI - [IgD myeloma. Presentation of a case and review of the literature]. AB - A case of IgD myeloma that began with high paraproteinaemia, BJ proteinuria of type and 40% marrow plasmacellular infiltration is reported. These onset data suggested a large tumoral mass and hence a poor prognosis. On the other hand, after subjecting the patient to 4 polychemotherapy cycles (alkeran and prednisone) CM disappeared from serum and urine and bone lesion progression stopped. It is also stressed that this from presents clinical (frequent extra osseous growth, presence of amyloidosis), laboratory (severe anaemia, renal insufficiency, BJ proteinuria) and particular prognostic features. PMID- 2314612 TI - [Induced pemphigus and brucellosis]. AB - A case of induced pemphigus occurring in a patient affected with a brucellosis is reported with emphasis on the definitive remission of the pemphigus after antibiotic therapy against brucellosis and in the absence of corticosteroid treatment. Attention is also drawn to a possible autoimmune mechanism of the pemphigus triggered by brucellosis. PMID- 2314613 TI - [Description of an unusual clinical picture of visual hallucinations (polyopsia, erythropsia) as expression of right temporo-occipital ischemia (visual association cortex, Brodman area 37]. AB - An unusual clinical picture (polypsia and erythropsia) as a consequence of an ischaemic lesion of the temporo-occipital junction, known as Brodman area 37 is reported. CT images showed that the lesion area was linked with the two particular function of visual association and memory peculiar to area 37 and, as is well known in the literature, predominant in right hemisphere damage. PMID- 2314614 TI - [Physiopathological significance of renal blood flow reduction in patients with essential arterial hypertension]. AB - a group of 120 patients suffering from E.A.H. divided into three age Plasma renal flow was reduced on average in all three groups. It is t this fact could support the hypothesis that the change in renal per y a pathogenic role in E.A.H. ss F1/hlp F2/que F3/ext F4/can F5/nxt F6/ins F7/up F8/dwn F9/fin PMID- 2314615 TI - [The renin-angiotensin-aldosterone system in liver cirrhosis]. AB - The role of the RAA system in the genesis of ascites in liver cirrhosis patients is not yet perfectly clear. The present study was conducted on 176 cirrhosis patients in order to investigate RAA system function, to assess the changes taking place in the various stages of the disease and to correlate such changes with the various kidney function parameters. The patients were divided into 3 groups as follows: Group I: patients without ascites on admission and with no history of the condition; Group 2: patients with ascites of recent onset and/or response to diuretic treatment; Group 3: patients with ascites not responsive to diuretic treatment. In Group 1, 19 patients (38%) reveal a significant reduction in renin activity together with portal hypertension and increased hydrosaline retention. In Group 2 renin activity was reduced in 4 patients (6%), aldosterone activity in 3 (4%). Progressive deterioration in liver function parameters and progressive activation of the RAA system combined with reduced sodiuria content were found in over 50% of these patients. The presence or absence of portal hypertension in this group was not related to significant changes in diuresis or sodiuria. In Group 3 renin was activated in 54 patients (89%), aldosterone in 58 (95%) and there was also a distinct reduction in sodiuria (96% of patients) and chloruria (100%). A substantial increase was also noted in the incidence of low blood sodium (53%) while portal hypertension was found in 97% of patients. On the basis of those data it may be hypothesised that high pressure inside the liver creates the stimulus for primary sodium retention. The decrease in effective blood volume after vasodilation, accentuated by low blood albumin and splanchnic venous stagnation may the stimulate the sympathetic nervous system and RAA system. Hyperaldosteronism only becomes the dominant factor in renal imbalance when the cirrhosis reaches the resistant ascites phase. PMID- 2314616 TI - [Intestinal ischemia: nosographic framework and risk factors]. AB - The diagnosis of intestinal ischaemia still presents numerous problems in terms of nosography, epidemiology, diagnosis and treatment with the result that it is more often excluded than diagnosed. The aim of the present study was to discover whether intestinal ischaemia was clinically identifiable by any specific early signs and symptoms and whether there were any concomitant risk factors. The medical reports on 44 patients consecutively admitted to the San Giovanni Battista Hospital, Turin in 1985-86 with suspected intestinal ischaemia were therefore examined. It was found that intestinal ischaemia was only occasionally (30% of cases) diagnosed at the onset of clinical symptoms. In the 10 patients with ischaemic colitis, the risk factor linked to the causes of the disease was systemic hypovolaemia arising in diffuse atherosclerosis. In the 8 cases of chronic ischaemia and the 26 of intestinal infarction the remote anamnesis revealed symptoms that should have aroused suspicion of intestinal ischaemia partly because the patients were suffering from widespread atherosclerosis. In fact a review of the risk factors for the onset of atherosclerosis (i.e. high blood pressure, smoking, dyslipidemia, obesity and age over 65) revealed that about 60% of the patients under study presented 3 or 4 them simultaneously. To conclude, the data emerging from the study indicate the existence of symptoms and risk factors to diffuse atherosclerosis that should permit the early diagnosis of intestinal ischaemia. PMID- 2314617 TI - [Unreliability of the clinical diagnosis in deep venous thrombosis of the lower limbs]. AB - 277 patients subjected to phlebography for clinically suspect acute deep venous thrombosis of the lower extremities have been examined. Instrumental examination evidenced the presence of thrombosis in 140 of them (50.5%) while in the remaining 137 (49.5%) in whom venography proved negative, it was possible to define the pathologies responsible for the clinical picture in 89% of cases. In out-patients, the incidence of thrombosis proved lower (46%, 65/141 patients) than that presented by patients already hospitalised for other pathologies (55%, 75/136 patients). No significant differences were observed in the incidence of clinical symptoms and signs between patients with thrombosis and patients without at phlebography, while as regards the distribution of risk factors, there was a greater incidence of the following: age over-65, cancers, recent surgery and fractures of the lower extremities in the group of patients suffering from thrombosis. Personal experience would therefore appear to point to the total fallibility of the clinical diagnosis of deep venous thrombosis of the lower extremities and the consequent need for a constant objective instrumental diagnostic approach to this type of pathology. PMID- 2314618 TI - [Influence of smoking on healing in patients with NSAID-induced peptic ulcer]. AB - The influence of smoking on the cure of patients with peptic disease under non steroidal antiphlogistic drugs. Observation over a 2-month period of 35 patients with peptic ulcer or erosive duodenitis related to the use of non-steroidal antiphlogistic drugs shows a significant delay in endoscopic cure in smokers, whether or not they have stopped smoking. PMID- 2314619 TI - [Chronic prophylaxis of urinary tract infections in diabetic patients]. AB - A mass screening of 600 diabetic revealed 240 (190 female and 50 male) with urinary infections. The comparative antibiotic efficacy (elimination) and tolerability of Cinoxacin and Norfloxacin were assessed in the treatment of these patients. The traditional protocol (2 daily doses for 10-20 days) was supplemented in every case by chronic prophylaxis (a single daily dose for 10 days each month for 6 months) that was designed to prevent recurrences and the development of chronic urinary infections. Cinoxacin was always found to be faster acting in antibacterial terms than Norfloxacin (at 10 days x2 = p less than 0.01; at 2 degrees, 4 degrees, and 6 degrees month x2 = p less than 0.05) providing a more complete and faster remission of the subjective symptoms, as well as being considerably better tolerated a both locally and systematically than Norfloxacin. PMID- 2314620 TI - [Efficacy of the disinfection of fiber endoscopes]. AB - The validity of routine disinfection of gastrointestinal fibroscopes is reported. The Authors present their work based on 204 tests performed on gastroscopes and colonoscopes after manual disinfection performed by skilled nurses. All the instruments were kept in a 1:16 solution of glutaraldehyde-phenate for 10 minutes. Microbiological tests were performed half on sterile solution flushed on the outer part of the endoscope and half into the bioptic channel. Different groups of tests are reported. When strict asepsis was observed in handling the endoscopes all tests demonstrated to be sterile. When the endoscopes were handled as in usual routine, i.e. without sterile gloves and so on, 20% of the tests showed the presence of bacteria: these were only of types present in the environment. No real pathogens or antibiotic resistant strains were observed. The total disinfection procedure showed to be easy and quick to perform. No allergic or toxic reactions were observed. The importance of this procedure as a routine one in all endoscopy units is stressed considering also that literature data demonstrate the efficacy of glutaraldehyde-phenate against hepatitis and AIDS viruses. PMID- 2314621 TI - [Bamifylline in the therapy of asthmatic syndromes. Efficacy and side effects vs delayed-action theophylline anhydride]. AB - Two homogeneous groups of 8 patients suffering from bronchial asthma or chronic obstructive bronchial pneumonia were treated with slow release theophylline anhydride or bamiphylline respectively, both products being given orally twice a day. The results showed that both drugs possess a powerful bronchodilatory action and therefore have a beneficial effect on subjective symptoms. Statistical analysis confirmed the absence of any significant difference between the two xanthine derivatives, both of which were well-tolerated though bamiphylline offered a slight advantage in this respect. In fact there were no side effects at all in the bamiphylline group whereas there was one case of moderate gastric intolerance in the group given theophylline anhydride, though it was not severe enough to warrant suspension of the treatment or reduction of the dose. PMID- 2314622 TI - [Polycythemia vera and hemoregulator hormones. Considerations on an unusual clinical case]. AB - The case is reported of a patient with polycythemia vera, who developed an anterior panhypopituitarism, due to an adenoma, some years later. The endocrine deficiency caused the return of the hemoglobin count and global red cell volume to the normal range. The finding suggests that in polycythemia vera the neoplastic growth is still partially responsive to normal hemoregulator factors. PMID- 2314623 TI - Selective uptake of gamma-[3H]aminobutyric acid by neural elements and vascular nerves of the rat intestinal submucosa. AB - Laminae of the rat intestinal submucosa were examined autoradiographically for gamma-[3H]aminobutyric acid ([3H]GABA) high-affinity uptake sites. In the presence of 10(-3) M beta-alanine, to prevent high-affinity uptake and localization of radiolabelled GABA by glia. [3H]GABA was accumulated into elements of Henle's or Schabadasch's plexus, and vascular nerves. Densely labelled fibres in the nerve plexus could be followed through the ganglia and interconnecting fasciculi, and often formed a dense neuropil in the ganglia. Cell soma were never labelled. Densely labelled fibres of the nerve plexus were sometimes found to be contiguous with fibres coursing with the blood vessels. All labelling could be prevented by the neural specific high-affinity uptake blocker, L-diaminobutyric acid (L-DABA; 10(-3) M). PMID- 2314624 TI - Fetal cortical transplants reduce motor deficits resulting from neonatal damage to the rat's frontal cortex. AB - Motor deficits in the execution of grasping movements of the right forelimb were compared in normal female Wistar rats, in animals which sustained a neonatal lesion of the left frontal cortex and in animals which received immediately after the lesion a transplant obtained from the frontal cortex of E16 embryos. Behavioral testing was carried out from postnatal day 48 (D48) to D108. The animals were placed at the center of a circular wire grid which was turned upside down so that they hung by their 4 paws at a distance of 40 cm above the floor. The precision of grasping movements of the right limb and the number of falls were recorded during a 1 min session of active moving across the grid. The lesioned subjects were most impaired on both motor indices whereas the grafted animals although performing slightly poorer than the controls were, however, less impaired than the lesioned animals. Fetal cortical transplants, therefore, seem to promote functional recovery from neonatal cortical damage. PMID- 2314625 TI - Changes in the discharge patterns of motor cortical neurones associated with volitional changes in stepping in the cat. AB - Extracellular recordings have been obtained from motor cortical neurones of cats walking along a horizontal ladder. We present responses obtained when the animal produced defined volitional changes in limb trajectory, and during different conditions of locomotion. Our results show substantial changes in discharge pattern of some cells under these different conditions. Encounters with displaced rungs produce marked changes in discharge pattern including some which precede foot contact and others graded to the magnitude and direction of displacement. PMID- 2314626 TI - Cocaine-induced cerebral vascular damage can be ameliorated by Mg2+ in rat brain. AB - Cocaine HCl (10 micrograms/ml) delivered perivascularly to the surface of the rat brain resulted in rapid contraction of pial arterioles, which reduced the diameters by 26% compared to controls. This was followed by venular vasospasm and rupture of postcapillary venules and micro-hemorrhages at postcapillary sites. Administration of Mg aspartate HCl, by intraarterial or intravenous infusion (1, 10 and 20 mumol/min), before or after the cocaine, produced dose-dependent inhibition (20-85%) of the cocaine-induced arteriolar spasms and prevention and attenuation of the venular vasculotoxicity and hemorrhaging. These data suggest that magnesium salts might be useful agents in the treatment of cocaine-induced intoxication and prevention of brain damage. PMID- 2314627 TI - Large reductions in composite monosynaptic EPSP amplitude following conditioning stimulation are not accounted for by increased postsynaptic conductances in motoneurons. AB - A compartmental neuronal model was used to show that increased compartmental leak conductances distal to the site of excitatory postsynaptic potential (EPSP) generation have little effect on EPSP amplitude but decrease half-width markedly. Using intracellular recording from cat hindlimb motoneurons, reductions of composite Ia EPSP amplitude by up to 70% unaccompanied by reductions in half width were seen following conditioning stimuli to hindlimb nerves. Appropriate condition-test intervals produced large reductions in EPSP amplitude that were unaccompanied by detectable increases in motoneuron conductance. These observations suggest that presynaptic inhibition and not increased postsynaptic motoneuron conductances is responsible for large EPSP amplitude reductions following conditioning stimulation. PMID- 2314628 TI - The GABAergic system of the dorsal cortex of lizards: a combined HRP-GABA immunohistochemistry study. AB - gamma-Aminobutyric acid (GABA)-like immunoreactive (GABA-LI) neurons were found throughout the mediolateral and rostrocaudal axis of the dorsal cortex. They were horizontal, vertical and multipolar cells, mainly distributed in layers 1 and 3. GABA-LI boutons were diffusely distributed in layers 1 and 3, as well as forming basket-like images around layer 2 pyramidal perikarya. Double labelling experiments indicate that GABA-LI cells are an origin of and a target for rostrocaudal intrinsic projections within the dorsal cortex. PMID- 2314629 TI - Stability of orthogonal arrays of particles in murine skeletal muscle and astrocytes after circulatory arrest, and human gliomas. AB - The effect of hypoxic conditions on the maintenance of orthogonal arrays of particles (OAP) in the plasma membranes of brain astrocytes, skeletal muscle cells of the mouse and of human glioma cells was investigated by means of freeze fracturing. Pieces of tissue were put in a moist chamber at 20 and 37 degrees C and fixed after different intervals up to 2 h. Muscle cell OAP are demonstrated 2 h after circulatory arrest irrespective of temperature. Astrocytic OAP are shown to be as stable as those in muscle cells at 20 degrees C. Also at 37 degrees C, intact OAP were observed although the membranes were strongly lesioned. We conclude that OAP in astrocytes are essentially more stable than reported in the literature. PMID- 2314630 TI - Differing actions of baclofen and 3-amino-propylphosphinic acid in rat neocortical slices. AB - Rat neocortical slices maintained in Mg2(+)-free Krebs medium developed spontaneous paroxysmal discharges which were attenuated or suppressed by the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen, occasionally accompanied by a slight hyperpolarisation, and antagonised by the specific GABAB receptor antagonist, 2-OH-saclofen. Over the same dose range, the GABA-analogue 3 amino-propylphosphinic acid (3-APA) caused a marked, prompt hyperpolarisation with little or no effect on the frequency of the discharges, although their amplitude was attenuated. In the presence of 2-OH-saclofen, 3-APA still induced a hyperpolarisation but the amplitude of the discharges was no longer affected. This marked difference in action between baclofen and 3-APA in the rat neocortical slices suggests there may be a heterogeneity of GABAB-receptors. PMID- 2314631 TI - Myosin heavy chain expression in developing rat intrafusal muscle fibers. AB - The immunocytochemical expression of several isoforms of myosin heavy chains (MHC) was determined in developing intrafusal and extrafusal fibers of the soleus muscle of prenatal and postnatal rats. At the onset of spindle assembly, both bag2 intrafusal myotubes and primary extrafusal myotubes bound a slow-twitch MHC antibody, whereas the bag1 and chain myotubes expressed a fast-twitch MHC isoform identical to that expressed by secondary extrafusal myotubes. Subsequently, developing intrafusal fibers began to express unique myosin isoforms, and ceased to express some of the myosin isoforms present initially. The initial similarity in MHC composition of intrafusal and extrafusal fibers suggests that these two kinds of mammalian muscle cell originate from a common pool of bipotential myotubes. Differences in MHC expression by intrafusal and extrafusal fibers in adult muscles might result from the effect of sensory neurons on the developing intrafusal myotubes. PMID- 2314632 TI - Vasopressin mRNA in parvocellular neurons of the rat suprachiasmatic nucleus exhibits increased poly (A) tail length following water deprivation. AB - Dehydration is associated with altered vasopressin (VP) gene expression in the rat hypothalamus; an increase in both arginine-vasopressin mRNA abundance and size (due to 3' poly(A) tail extension) has been observed previously. We have now shown that the effects of dehydration are not restricted to the magnocellular AVP neuronal systems since VP mRNA in the suprachiasmatic nucleus (SCN) exhibits a progressive increase in poly(A) tail length during dehydration. No significant increase in VP mRNA abundance was found. Similar kinetics of poly(A) tract extension in the SCN and magnocellular supraoptic nucleus implies a common regulatory mechanism which appears to be distinct from osmotic upregulation of VP transcript abundance. PMID- 2314633 TI - Protein synthesis as a function of depth in slices of rat hippocampus. AB - Physiologically viable slices of rat hippocampus were incubated in radiolabeled valine, then cut into 20 microns serial sections to evaluate the profile of protein synthesis through the depth of the slice. Maximum radiolabel incorporation was observed near the center of the slice, while at the upper (gas interface) and lower (liquid interface) surfaces radiolabel incorporation per section was reduced by about 30% and 90%, respectively. The results suggest that in properly slices damage due to slicing may be less important to cell viability than are limits on oxygen diffusion into the tissue. PMID- 2314634 TI - Electroimmunoblotting of neuropeptide Y: application to the rat vas deferens. AB - In this study we have optimized the electroimmunoblotting conditions for neuropeptide Y (NPY). NPY standards and samples extracted from the rat vas deferens were separated on urea-sodium dodecyl sulphate gels. Densitometric scanning of the Coomassie Blue-stained gels allow a semi-quantitative analysis of NPY in the range of approximately 10(-11) to 10(-8) mol of NPY. Electroimmunoblotting of NPY was also shown to be best achieved overnight at 4 degrees C and with NC membranes of 0.22 micron. Under these conditions NPY extracted from the vas deferens has been efficiently electroimmunoblotted. Higher molecular weight NPY-reactive peptides were also detected that may be related to proteolytic processing of the NPY precursor. PMID- 2314635 TI - The role of the hypothalamic paraventricular nuclei for the regulation of pineal melatonin synthesis: new aspects derived from the vasopressin-deficient Brattleboro rat. AB - There is evidence for an involvement of the hypothalamic paraventricular nuclei (PVN) in the regulation of pineal melatonin synthesis in rats. Since electrical stimulation of the PVN or the systemic administration of arginine-vasopressin (AVP) result in a depression of the nocturnal melatonin surge, this neuropeptide appears to be pivotal for the transduction of PVN-efferent, pinealopetal signals. We therefore used an AVP-deficient animal model, the Brattleboro rat, to further investigate the mechanisms responsible for pineal regulation. Anesthetized adult male animals received 2 min of bilateral electrical stimulation of the PVN either during the day or at night. Thirty min later, pineal glands were removed and pineal N-acetyltransferase (NAT) activities and melatonin contents were determined. Stimulation resulted neither during the day nor at night in any significant alterations of pineal NAT activity or melatonin content when compared to control or sham-stimulated animals. These data further support the proposed modulatory role of AVP for the regulation of melatonin synthesis in the Epiphysis cerebri of genetically intact rats. PMID- 2314636 TI - Thioridazine chronic administration: a behavioural and autoradiographic study. AB - In rats the effects of chronic treatment with thioridazine (5 mg/kg orally administered for 22 days) were studied by means of behavioural supersensitivity to apomorphine and by means of dopamine (DA) receptors quantitative autoradiography. Locomotion and stereotypies induced by apomorphine increased after thioridazine chronic administration, whereas grooming behaviour decreased. Autoradiographic data showed an increase in DA receptors density both in the striatum and in the olfactory tubercle, to which the increase in stereotypies and locomotion could be respectively attributed. DA receptors increased also in the medial and dorsal frontal cortex. Moreover a decrease in DA receptors density appeared in the nucleus accumbens septi and in the lateral frontal cortex. Receptors decrease found in these regions might be associated with thioridazine induced chronic inactivation of A10 DA neurons, to which the antipsychotic effect of the drug is attributed. PMID- 2314637 TI - Effect of chronic GM1 ganglioside administration on passive avoidance retention in mice. AB - Chronic administration of GM1 ganglioside to C57BL/6 mice during development improved passive avoidance retention. A significant weight increase was also evident in the treated animals in comparison with the control group. The results are discussed in terms of the possible effects exerted by GM1 upon the cholinergic mechanisms of this inbred strain. PMID- 2314638 TI - Ultrasonic vocalization in rats produced by cholinergic stimulation of the brain. AB - Neurotransmitters involved in production of ultrasounds in rodents have not yet been identified. It is also not known whether brain mechanisms regulating production of ultrasounds and audible sounds are similar or different. The present study provides the first report that intracerebral injection of an acetylcholine agonist, carbachol, in rats induces ultrasonic vocalization. Since the same agent can induce audible vocalization in cats, the finding suggests a possible common neurochemical substrate underlying production of sonic and ultrasonic vocalization in mammals. The data accumulated to date indicate also that these two kinds of vocalization may play a homologous role in animal communication. PMID- 2314639 TI - The influence of cocaine self-administration on in vivo dopamine and acetylcholine neurotransmission in rat caudate-putamen. AB - Presynaptic dopamine and acetylcholine transmission in the anteroventral (limbic) caudate-putamen were studied by microdialysis in freely moving rats during cocaine self-administration sessions. Acute cocaine exposure elevated dopamine (DA) overflow in drug-naive animals. However, during repeated cocaine administration, the drug-induced elevation of DA was attenuated in animals previously exposed (during the prior 9 days) to cocaine. The diminished dopamine response in repeatedly treated animals while self-administering cocaine was speculated to be due to increased activity of DA transport carrier and/or supersensitive receptors modulating DA release. During repeated cocaine administration, extracellular acetylcholine levels in animals previously exposed to cocaine were found to be significantly decreased compared with controls. The findings of the study may suggest a functional development of supersensitive DA receptors postsynaptic to the DA terminal (located on cholinergic neurons) as a consequence of previous cocaine exposure. Such supersensitivity would allow for a reduced DA signal to be amplified at the postsynaptic level during repeated cocaine self-administration. PMID- 2314640 TI - Developmental delays associated with prenatal alcohol exposure are reversed by thyroid hormone treatment. AB - Exposure to alcohol in utero has been associated with hypothyroidism and a variety of developmental defects characteristic of thyroid dysfunction. The present work examined whether these abnormalities could be reversed in infant rats treated with thyroid hormones. Subjects were offspring of dams which were on the following diet regimen during gestation: (1) free access to liquid diet containing ethanol (alcohol pups); (2) an equal volume of isocaloric liquid diet (pair-fed pups); or (3) ad libitum control diet (control pups). Neonates from each group were foster-nursed by control dams, and received triiodothyronine (T3; 0.1 mg/kg/day; s.c.) or saline treatments on postnatal days 1 to 10. The alcohol neonates displayed reduced serum thyroxine which was restored to normal by postnatal day 14. In addition, these pups showed a delayed appearance of developmental landmarks, including righting reflex, dental eruption, auditory startle response and eye opening. The retarded incisor eruption and eye opening were reversed in alcohol pups by T3 treatments. The present data suggest that at least some of the developmental abnormalities associated with prenatal alcohol exposure are attributable to perinatal hypothyroidism and can be restored by early hormone replacement therapy. PMID- 2314641 TI - Increased expression of the embryonic form of a developmentally regulated mRNA in Alzheimer's disease. AB - There is increasing evidence that an aberrant sprouting response may contribute to some of the neuronal alterations observed in Alzheimer's disease (AD). In this study, we demonstrate that in the rat CNS, sprouting results in the reinduction of the embryonic form of the mRNA for alpha-tubulin. The fetal form of alpha tubulin mRNA was also elevated in the hippocampus obtained from five AD patients, as compared to five elderly controls. These results suggest that the reexpression of embryonic forms of cytoskeletal proteins, in association with an aberrant sprouting response, may contribute to the neuropathological alterations in AD. PMID- 2314642 TI - Neuronal hypertrophy in the human supraoptic and paraventricular nucleus in aging and Alzheimer's disease. AB - In the literature, activation of the hypothalamo-neurohypophyseal system (HNS) in normal aging has been demonstrated in rat and human. This activation might be secondary to an age-related decline in vasopressin binding sites in the kidney, or to cell loss in the supraoptic (SON) and paraventricular nuclei (PVN) and/or to an age-related decline in noradrenergic (NA) innervation of the hypothalamus. This study shows neuronal hypertrophy in SON and PVN in normal aging and an additional hypertrophy in Alzheimer's disease. No cell loss could be demonstrated in both conditions. PMID- 2314643 TI - Calcitonin gene-related peptide containing primary afferent fibers synapse on primate spinothalamic tract cells. AB - Spinothalamic tract (STT) cells were identified by intracellular injection or retrograde labeling with horseradish peroxidase (HRP) in the primate spinal cord. Using immunohistochemical techniques, a population of primary afferents containing calcitonin gene-related peptide (CGRP) is demonstrated in synaptic contact with these neurons. Large glomerular type CGRP terminals with morphology considered typical of primary afferent fibers are occasionally observed in contact with STT profiles in laminae I and IIo; however, this morphological type targets STT profiles chiefly in the deeper dorsal horn (laminae III, IV and V). In contrast, the majority of CGRP terminals contacting STT profiles in the superficial dorsal horn (laminae I and IIo), are small, round or oblong shaped terminals. Thus, evidenced by these data, the absence of large, glomerular type terminals does not rule out primary afferent input. PMID- 2314644 TI - Responses of reticulospinal neurons in the lateral reticular nucleus area of the rat to cutaneous noxious and non-noxious stimulation. AB - Response properties of reticulospinal neurons in the lateral reticular nucleus (LRN) area to natural cutaneous stimulation were investigated systematically in 45 urethane-anesthetized rats by using extracellular recording techniques. A total of 64 neurons were tested with peripheral stimuli, of which 19 were responsive only to noxious stimuli; 7 responsive to both noxious and non-noxious stimuli; 4 responsive only to non-noxious stimuli; and 34 not responsive to any cutaneous stimuli. Both the noxious and non-noxious receptive fields were large and bilateral. Among the neurons responding to noxious stimuli, the majority (72%) was excited. This study provides evidence that some reticulospinal neurons in the rat LRN area are involved in the mechanisms of nociception. PMID- 2314645 TI - Vasopressin-secreting neurones of the paraventricular nucleus respond to oropharyngeal application of hypertonic saline. AB - Responses of electrophysiologically identified vasopressin (VP)-secreting neurones of the hypothalamic paraventricular nucleus in the rat were recorded following the application of hypertonic saline (2-4 M) to the tongue and oropharynx. Fourteen of the 15 VP-secreting neurones were excited by the stimulus, response onset occurring within a few seconds. Of the 5 neighbouring unidentified neurones, or those identified as projecting to the median eminence, 3 were also found to respond to the stimulus. All of the responses were sustained during the period of application and were reversed following wash-off with distilled water, when neurones were found to be substantially inhibited. The results of this study indicate a role of ascending gustatory sensory afferent innervation as a predictive indicator of changing plasma osmotic pressure. PMID- 2314646 TI - "Near death" and live responses. PMID- 2314647 TI - Open letter re: feminism and nursing. PMID- 2314648 TI - Critical thinking in the nursing curriculum. AB - In increasing the emphasis on critical thinking in the nursing curriculum, there is concern that it will become another unit of content competing with other units that must be included somewhere in the curriculum. Critical thinking is much more than this. It is a combination of an attitude of inquiry, supported by a knowledge base and enhanced by skill in application. Critical thinking is an approach to inquiry where both students and faculty examine clinical and professional issues and search for more effective answers. Unfortunately, there is no simple, magic "how to" formula to guide faculty in developing these skills among nursing students. PMID- 2314649 TI - A faculty learns how to make self-pacing work. AB - Today's nursing faculty employ self-pacing, independent study, formative evaluation, summative evaluation, competency-based learning, and flexible scheduling, to name but a few methods. But when is enough, enough? One faculty learned that each new method brings its own problems. Brubaker tells how this faculty reached those compromises that promised the best path through the maze of educational technology. PMID- 2314650 TI - Student evaluations: are they an appropriate criterion for promotion? AB - Are student evaluations appropriate tools for evaluating faculty for promotion? Dennis gives a balanced perspective on the arguments both pro and con. Can a student who is just learning a subject judge a faculty member's command of the subject matter? What factors can a student adequately assess-presentation? subject matter knowledge? motivational power? Dennis looks at the dangers and benefits of adding student evaluations to the compendium of evidence for faculty promotion. PMID- 2314652 TI - At New York University, the division of nursing develops a model for nursing and medical school collaboration. PMID- 2314651 TI - Developing a BSN program across two institutions: Arizona State University West Campus/Glendale Community College. The adjuvant model. AB - It is an era when new and creative academic linkages are being forged in nursing education. Many unique programs are coming into existence in service of the goal of promoting baccalaureate education for nurses. Davids and Laeger describe a particularly complex and sensitive program of BSN education developed across two institutions. PMID- 2314653 TI - Care for the elderly. PMID- 2314654 TI - Nursing home administration: a key role for the gerontological nurse. PMID- 2314655 TI - Innovative programs and services for the elderly. PMID- 2314656 TI - Clinical nursing rounds: a model for elder care planning at the bedside. PMID- 2314657 TI - Rehabilitation nurse specialist practice in an acute care setting. PMID- 2314658 TI - Discharge planning for the elderly: implementation of a continuing care role. PMID- 2314659 TI - The geriatric consult team: service and advocacy for elders. PMID- 2314660 TI - The elder assessment team: protecting elders from abuse and neglect. PMID- 2314661 TI - Assessing patient placement at Freedom Square Retirement Community. PMID- 2314662 TI - The frail elderly: those 85 and over. PMID- 2314663 TI - Health care services for older adults: geriatric programs at the Johnston R. Bowman Health Center for the Elderly. PMID- 2314664 TI - On the scene: section 2--Rush-Presbyterian-St. Luke's Medical Center. PMID- 2314665 TI - Geriatric medicine unit. PMID- 2314666 TI - Nursing home liaison program. PMID- 2314667 TI - The Rush Alzheimer's Disease Center. PMID- 2314668 TI - Nursing clinics and senior centers. PMID- 2314669 TI - The teaching nursing home program. PMID- 2314670 TI - Church-based geriatric care. PMID- 2314671 TI - A unique multidisciplinary approach for urban geriatric home care. PMID- 2314672 TI - The gerontological nursing program. PMID- 2314673 TI - On the scene: section 1--Beth Israel Hospital. PMID- 2314674 TI - Innovative community-based health care for the elderly: a university-community partnership. PMID- 2314675 TI - Unstructured strategic decision making by nurse administrators when allocating resources. PMID- 2314676 TI - Counseling medical patients about cigarette smoking: a comparison of the impact of training on nurse practitioners and physicians. AB - Health providers believe that eliminating smoking is an important health promotion goal, but physicians and nurse practitioners may differ in the implementation of that belief. To determine whether nurse practitioners or physicians were more likely to counsel smokers to quit smoking, 12 internal medicine nurse practitioners (100 percent female) and 40 internal medicine physicians (30 percent female) were studied at four San Francisco Bay-area Kaiser Permanente Medical Centers, both before and after training in smoking-cessation counseling. In addition, exit phone surveys of at least 15 smokers per participant were completed as soon as possible following an office visit to the participant (269 nurse practitioner patients; 948 physician patients). It was found that nurse practitioners discussed smoking with patients more often than did physicians (64 percent vs. 50 percent; p less than 0.001), asked patients more often whether they were interested in quitting (49 percent vs. 40 percent; p less than 0.01), distributed more smoking-cessation literature to patients (37 percent vs. 25 percent; p less than 0.001) and made more follow-up appointments about smoking (36 percent vs. 19 percent; p less than 0.001). These differences in counseling behavior between the two groups were not explained by differences in patient characteristics of the two groups. The authors concluded that, given the same training, nurse practitioners are more likely to counsel smokers about quitting than are physicians. PMID- 2314677 TI - An introduction to using children's drawings as an assessment tool. AB - This article is intended to familiarize the ambulatory care provider with possible uses of children's drawings as assessment tools. Drawings can be a useful adjunct in detecting perceptual-motor difficulties and developmental delay, and can provide clues to self-image and family dynamics. Piaget's theory of cognitive development provides a framework to evaluate the child's intellectual development as reflected in drawings. The developmental scales of Koppitz are presented as a practical screening tool. The Koppitz scales include both developmental norms and items that might indicate emotional problems. Observing the child's drawing of the family provides clues to family dynamics. Becoming highly skilled in the evaluation of children's drawings requires a familiarity with neurophysiology, education, psychology, and psychoanalytic and developmental theory, along with intuition and practice. This article presents an introduction to evaluating children's drawings. PMID- 2314678 TI - Methylxanthines and fibrocystic breast disease: a study of correlations. AB - Daily methylxanthine ingestion from drug and dietary sources was studied by means of questionnaires from a sample of 102 women who visited the office of a radiologist for xeromammograms. The mammograms were used to measure the level of fibrocystic breast disease. Fibrocystic breast disease was found to be positively correlated with both caffeine and total methylxanthine ingestion. These positive findings are discussed in light of the fact that most recent studies of this link have been negative. PMID- 2314679 TI - The issue of third-party reimbursement--advice for nurse practitioners from a national expert. Interview by Linda J. Pearson. PMID- 2314680 TI - Fluids, electrolytes, and acid-base balance. PMID- 2314681 TI - 10 questions recruiters will ask. PMID- 2314682 TI - Make the most of your time...by trusting yourself. PMID- 2314683 TI - Handling hemorrhage wisely. PMID- 2314684 TI - Meeting Kevin halfway. PMID- 2314685 TI - A.I.D.S. Update: pros, cons of Hickman catheter. PMID- 2314686 TI - A.I.D.S. update: endocrine complications. PMID- 2314687 TI - A.I.D.S. update: how infection occurs. PMID- 2314688 TI - A.I.D.S. dilemma. Doing the right thing. PMID- 2314689 TI - Action stat! Cocaine overdose. PMID- 2314690 TI - Right ventricular infarction. How to recognize hidden cardiac damage. PMID- 2314691 TI - Treating a stab wound. PMID- 2314692 TI - Bob was simply dying. PMID- 2314693 TI - Dealing fairly with medication errors. PMID- 2314694 TI - Offer families hope...or help them let go? The story of Anna, a brain-injured patient. PMID- 2314695 TI - Pulse oximetry. An easy way to check oxygen saturation. PMID- 2314697 TI - IV therapy. Reducing the risk of infection. PMID- 2314696 TI - How to insert a small-bore feeding tube safely. PMID- 2314698 TI - Calling in sick. How to decide. PMID- 2314699 TI - When overcompliance means trouble. PMID- 2314700 TI - Giving intradermal injections. PMID- 2314701 TI - Just nervous enough. PMID- 2314702 TI - Assessing abdominal pain in a postoperative patient. PMID- 2314703 TI - A healing hug. How a caring gesture broke through a patient's heartache. PMID- 2314705 TI - The research process. PMID- 2314704 TI - Symposium on immobility. The role of community nurses. PMID- 2314707 TI - Barking up the right tree. PMID- 2314706 TI - The psychiatric CNS 4. The nurse as therapist. PMID- 2314708 TI - Wound management. Tattoos and tattoo removal. PMID- 2314709 TI - Career profile: all thanks to Sonia. PMID- 2314710 TI - That was the year that was. PMID- 2314711 TI - Symposium on immobility. Care after a stroke. PMID- 2314712 TI - Acquired immunodeficiency syndrome: the agenda for the 1990s. PMID- 2314713 TI - Expanding the focus of human immunodeficiency virus prevention in the 1990s. PMID- 2314714 TI - The increasing role of primary care in the management of HIV-infected patients. PMID- 2314715 TI - Dissemination of Pneumocystis. PMID- 2314716 TI - Changes in AIDS risk behavior among intravenous drug abusers in New York City. AB - Forty newly admitted patients to a methadone treatment clinic in New York City were interviewed to assess their patterns of intravenous (IV) drug abuse, sexual activity, and other risk behaviors for the acquired immunodeficiency syndrome (AIDS). The study revealed a marked decline in needle sharing since 1984 (46% to 14%), despite a concurrent doubling of the number of weekly IV drug injections per subject (10 to 21). High rates of promiscuous heterosexual activity were noted among men (80% said they were currently active with more than one woman), while the rates of condom use were low, as reported by both men and women (less than 30%). Recent reduction in weight were reported by 40% of subjects, and the average body mass of all individuals was subnormal. Thus, despite an apparent decline in needle sharing, high risk sexual behavior is apparently persisting, drug use is increasing, and nutritional deficits are prevalent among IV drug abusers. Synergism of these factors should be considered in the manifestation of HIV infection among IV drug abusers. PMID- 2314717 TI - Assessment of AIDS knowledge in selected New York State sexually transmitted disease clinics. AB - A 1988 survey regarding the level of knowledge about acquired immunodeficiency syndrome (AIDS) among 505 clients of sexually transmitted disease (STD) clinics demonstrated 80% correct responses. However, 13% thought AIDS could be transmitted via sharing utensils, and 51% were unaware that acquiring another STD could increase one's risk of human immunodeficiency virus (HIV) infection. In addition, only 10% always used condoms. An average 69% of patients obtained their AIDS information from newspapers, magazines, television, or radio; and 30% acquired information from medical or clinic staffs. In response to this survey, a videotape on AIDS was developed to show to patients of STD clinics while they are waiting to see a physician. PMID- 2314718 TI - AIDS education: evaluation of school and worksite based presentations. AB - From 1986 through mid-1988, the Westchester County (NY) Health Department made AIDS education presentations upon request to junior and senior high school students and to adult educators and supervisors. In 1987, an evaluation component was added to measure the effectiveness of the presentations in increasing knowledge on AIDS-related topics. Questionnaires were field tested in a pilot study. During 1988, pre- and post-tests were administered 10-14 days before and after each scheduled presentation. Multivariate linear regression on the 847 pre- and 574 post-tests that were returned shows a statistically significant pre test/post-test difference, controlling for test type, age, and gender, in both overall score (t = 9.00, p less than 0.0001) and in total number of questions answered rather than left blank (t = 6.27, p less than 0.0001). In logistic analyses controlling for test type, age, and gender, the greatest post-test improvements were in questions about differences between AIDS and HIV-related disorders (then called ARC) (adjusted odds ratio, 1.86; 95% confidence limits, 1.65, 2.10); AIDS and drug use (1.73; 1.40, 2.14); sexual practices and AIDS (1.64; 1.40, 1.91); and the definition of AIDS (1.52; 1.29, 1.81). There was also significant post-test improvement on questions dealing with risks in social proximity to persons with AIDS, virus transmission by persons with AIDS, and differences between AIDS and HIV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314719 TI - AIDS behind bars. Epidemiology of New York State prison inmate cases, 1980-1988. AB - During the last five years, AIDS has become the preeminent health care problem in New York State correctional facilities. Through December 31, 1988, 915 cases of AIDS had been diagnosed among inmates. This represented approximately 1% of the cumulative AIDS cases in the United States, 4% of those in New York State, and 40% of those reported in state correctional systems nationwide. An analysis of epidemiologic data on these cases showed an annual increase in cases from 3 in 1981 to 227 in 1988, with an incidence greater than 400 per 100,000 inmates per year over the past four years. While most cases occurred in males (96%), females had the same high incidence rates (compared to the general population, in which female rates are one-eight of males). Forty-seven percent of infected inmates were Hispanic, 38% black, and 13% white. Pneumocystis carinii pneumonia was the most common diagnosis (65%), while Kaposi's sarcoma was rare (3%). Previous intravenous drug use has been the major risk factor, seen in 95% of cases. A comparison of 54 inmate AIDS cases with 107 matched and 196 unmatched controls showed that inmates in whom AIDS developed had significantly lower white blood cell counts on entry into prison, lower hematocrits and serum albumin levels, and higher serum glutamic oxaloacetic transaminase and globulin counts. Through July 1989, 643 (70%) of these 915 inmates had died of AIDS, and HIV infection and AIDS account for 68% of recent inmate deaths. PMID- 2314720 TI - A seroprevalence survey for human immunodeficiency virus antibody in mentally retarded adults. AB - The prevalence of human immunodeficiency virus (HIV) infection among adults who are mentally retarded is not known. Policies for those in residential settings are being established despite incomplete information. Knowledge regarding HIV seroprevalence would enable administrators to make more effective policy decisions concerning testing and HIV prevention. Discarded sera from mentally retarded adults were anonymously tested for HIV antibody. Sera were collected from a health facility in Westchester County, NY, that provides care to developmentally disabled adults. After identifications were removed, sera were coded and linked to demographic and clinical variables from hospital and laboratory records. Sera came from individuals living in both institutional and less restrictive community settings in metropolitan New York City and more distant locations in New York State, all of whom were seen by the above facility. No HIV antibody was detected in sera from 241 mentally retarded adults. This study suggests that the prevalence of HIV antibody in mentally retarded adults is not high. Mandatory screening programs may not be appropriate for these individuals. Monies might be better spent on educational programs directed at AIDS prevention, and further development of ethical and safe policies for those who are mentally retarded. PMID- 2314721 TI - Thoracic lymphadenopathy and disseminated Pneumocystis carinii in AIDS. PMID- 2314722 TI - Deep venous thrombosis in patients with AIDS. PMID- 2314723 TI - Resolution of cavitary Pneumocystis carinii pneumonia. PMID- 2314724 TI - AIDS legislation needed. PMID- 2314725 TI - Physicians needed to work with AIDS patients. PMID- 2314727 TI - Food and Drug Administration halves dosage for AZT. PMID- 2314726 TI - Extent of underreporting of AIDS documented in South Carolina. PMID- 2314728 TI - Growing role of bacterial infections in AIDS-related morbidity and mortality. PMID- 2314729 TI - Perinatally acquired HIV infection: AIDS' youngest victims. PMID- 2314730 TI - Some thoughts on undergraduate medical education. PMID- 2314731 TI - Cefixime: in vitro sensitivity of respiratory and urinary tract infection organisms. PMID- 2314733 TI - Wellington Area Health Board. PMID- 2314732 TI - Fluoxetine and hyponatraemia. PMID- 2314734 TI - Complications of legal abortion. PMID- 2314735 TI - Conduct unbecoming a consultant. PMID- 2314736 TI - Fluconazole for fungal disease. PMID- 2314738 TI - Prophylactic antibiotics for colorectal surgery. PMID- 2314737 TI - NZMA complaint. PMID- 2314739 TI - AIDS in New Zealand. PMID- 2314740 TI - AIDS in Thailand. PMID- 2314741 TI - The prevalence of immature respiratory control in a neonatal population. AB - Cot death could be the result of chance coincidence of an adventitious challenge and a baby ill-equipped to meet it. This work was designed to test the hypothesis that there is a subpopulation of babies who lack the appropriate responses to hypoxia and hypercapnia which would enable them to overcome the effects of, for instance, nasal obstruction. The responses of 630 babies to air mixtures which induced significant changes in ventilation in the overwhelming majority, were recorded in a short protocol in which both the addition and withdrawal of hypercapnia and of hypoxia were effected. The results of each test were placed in one of five categories; in 13.6% there was no response to hypoxia, and in 2% the ventilation fell in hypoxia to a significant degree. The study confirms the existence of a subgroup of normal babies with little defence to the respiratory loading of mild upper respiratory tract infections. PMID- 2314742 TI - Risk factors for low birthweight in New Zealand, 1981-83. AB - This paper describes the patterns of risk factors for low birthweight in a cohort of New Zealand births. The trend of low birthweight with maternal age and parity was U-shaped. Maori mothers had the highest (79.38/1000 livebirths) and Pacific Island mothers the lowest (39.88/1000), rates of low birthweight infants. There was an indication that the risk for Pacific Island mothers was modified by the mother's place of birth. Compared to nonMaori nonPacific Island New Zealand born women, the risk was high for Pacific Island New Zealand born women (RR = 1.27, 95% CI 1.04-1.56), but low for nonNew Zealand born Pacific Island mothers (RR = 0.70, 95% CI 0.61-0.79). The risk for Maori mothers increased if the father was also of Maori ethnic origin. The risk of a low birthweight infant increased (p less than 0.001) with social class, and the rate was high among exnuptial births (75.25/1000 live births). The rates of low birthweight for nonMaori and Pacific Island births in the South Island were similar to those in the North Island, but among Maori births the rate in the South Island (RR = 0.64, 95% CI 0.51-0.82) was lower than in the North Island. PMID- 2314743 TI - Prader-Willi syndrome in New Zealand: a survey of 36 affected people. AB - The Prader-Willi syndrome consists of infantile hypotonia, failure to thrive, hypogonadism and developmental delay. It was first described in 1956. Later in life hypotonia improves. Between the age of two and four obesity becomes noticeable and between six and ten there is uncontrollable behaviour. A survey has been carried out of the 36 known cases in New Zealand and the pattern of the disease is similar to that elsewhere. In most cases the diagnosis was not established until between the ages of six and 10 when the obesity was marked and uncontrolled behaviour a problem. Early control of the obesity is helpful. PMID- 2314744 TI - Survey of neurological problems with amiodarone in the New Zealand Intensive Medicines Monitoring Programme. AB - Early in the monitoring of amiodarone it was evident that neurological events were unexpectedly frequent. A survey was then undertaken to measure the frequency of such events and to gain some impression of their clinical importance. The method of survey was the completion of questionnaires by doctors when patients were being reviewed. There was a 63.6% response rate and questionnaires were evaluated for 408 patients. There were 192 events assessed as being adverse reactions from a group of nine types of neurological events in 112 patients. Paraesthesiae, ataxia, vertigo and tremor were the most common (7-9%). The overall rate of neurological reactions was 27.5%. The individual reactions are examined as are dose relationships. PMID- 2314745 TI - Nursing in the computer age. PMID- 2314747 TI - Information technology and the computer. PMID- 2314746 TI - New age nursing. PMID- 2314748 TI - Piri ki nga tangaroa: in anticipation of better days. PMID- 2314749 TI - Stresses and strains. PMID- 2314750 TI - The compact. Interview by Glanda McCallum. PMID- 2314751 TI - Sun cancer. PMID- 2314753 TI - National campaign action. PMID- 2314752 TI - Know your rights. PMID- 2314754 TI - If AMA really wants to help ... PMID- 2314755 TI - A unique LPN to ADN bridge program. PMID- 2314756 TI - Agency nurses--whose liability? PMID- 2314757 TI - Modular nursing: partners in professional practice. PMID- 2314758 TI - Nurse liaison: bridging the gap. PMID- 2314759 TI - Nursing exchange: a new experience. PMID- 2314760 TI - Resurgence of nurse assistants in acute care. PMID- 2314761 TI - A self-care approach to today's challenges. PMID- 2314762 TI - The best approach is doing "nothing". PMID- 2314763 TI - The nurse's role in a team conference. PMID- 2314764 TI - From research to utilization: bridging the gap. PMID- 2314765 TI - Do head nurses include staff nurses in problem-solving? PMID- 2314766 TI - Cost containment and the short-stay needs of surgical patients. PMID- 2314767 TI - Cross-training: practicing effectively on two levels. PMID- 2314768 TI - Doing the impossible: managing ICU with no head nurse. PMID- 2314769 TI - Old loyalties in the new organization. PMID- 2314770 TI - Dealing with chemical dependency. PMID- 2314771 TI - Dealing with the RN shortage: one strategy that worked. PMID- 2314772 TI - Uveoparotid fever. A case report. PMID- 2314773 TI - Radiotherapy in the management of recurrent ameloblastoma. A long term follow-up of a case. PMID- 2314774 TI - More on endocarditis guidelines. PMID- 2314775 TI - Mosaicism in chorionic villus sampling: an association with poor perinatal outcome. AB - Prenatal diagnosis by first-trimester chorionic villus sampling was successful in 4319 pregnancies involving 4395 fetuses. Cytogenetic information was obtained by both rapid cytotrophoblastic preparation and monolayer mesenchymal tissue culture. Chromosomal mosaicism was present in 55 of 4319 (1.3%). The abnormal cell line involved the cytotrophoblast in 79.6% of the mosaic specimens. None of the abnormalities found in the cytotrophoblast were confirmed in the fetus when the tissue culture was normal, supporting the belief that the cells of the mesenchymal core more truly reflect the chromosomal constitution of the fetus. However, a significant increase in the perinatal loss rate in the placental mosaic group was noted when compared with the nonmosaics: 16.7 versus 2.7% (P = .0001). These findings suggest that placental mosaicism may be a cause of perinatal loss. PMID- 2314776 TI - Acute hypoxemia does not affect the umbilical artery flow velocity waveform in fetal sheep. AB - The present study in sheep was undertaken to test whether acute fetal hypoxemia causes abnormalities in the umbilical artery velocity waveform. A 1-hour period of hypoxemia was induced in six chronically catheterized fetal sheep by reducing the inspired oxygen content of the ewe. During hypoxemia, the ratio of the systolic to diastolic velocity did not change significantly compared with controls. From this experimental evidence, we conclude that normal Doppler waveforms in the umbilical artery do not necessarily imply fetal normoxemia in sheep and that, because a direct cause-effect relationship has not been established, fetuses that have abnormal waveforms are not necessarily hypoxemic. Whether this is also true in humans remains to be shown. PMID- 2314777 TI - Potential human teratogenicity of frequently prescribed drugs. AB - Published data regarding the human teratogenic potential of 157 drug components that are frequently prescribed to outpatients in the United States were evaluated according to a protocol developed for TERIS, an automated clinical teratology resource. This protocol stipulates that a bibliographic search be performed on each agent, a brief narrative summary of the available teratologic information prepared, and a risk rating assigned. The ratings are determined by consensus of five clinical teratologists, who independently assess the magnitude of teratogenic risk associated with each agent under usual therapeutic conditions as "none," "minimal," "small," "moderate," "high," and "undetermined." Forty-nine percent of the components of these frequently prescribed drugs had insufficient published information available to assess the risk of human teratogenicity. Of the agents that could be rated, the teratogenic risk in usual therapeutic doses was considered to be minimal or less in 92.5%. Many of these agents have also been assigned Pregnancy Categories by the United States Food and Drug Administration (FDA) according to a system designed to provide therapeutic guidance. There was no more agreement than that expected by chance between TERIS ratings and the FDA Pregnancy Categories for 83 agents that were classified according to both systems. We believe that the FDA Pregnancy Categories should not be used to provide counseling regarding the risk of teratogenic effects to women who have taken medication during pregnancy. Such counseling should be based on a more comprehensive evaluation of the teratologic literature and clinical situation, but need not involve consideration of the therapeutic benefit of the agent. PMID- 2314778 TI - Protein/creatinine ratio in random urine specimens for quantitation of proteinuria in preeclampsia. AB - Protein/creatinine ratio (mg/g) in random urine samples was measured in 35 preeclamptic patients and 70 healthy pregnant women. We found a close correlation between the protein/creatinine ratio in random urine samples and both the 24-hour protein excretion and the 24-hour protein/creatinine ratio in the preeclamptic patients. The ratio did not exceed 200 mg/g in any of the 70 healthy pregnant women; therefore, ratios below this value can be considered normal. We conclude that determination of the protein/creatinine ratio in random urine specimens may be a simple method for quantitation of proteinuria in preeclampsia. PMID- 2314779 TI - Quality of prenatal care; selected social, behavioral, and biomedical factors; and birth weight. AB - Two hundred two poor, mainly black women were studied to assess the effects of selected social, behavioral, and biologic factors on birth weight. A path analysis was used to model hypotheses about the interrelationships among these variables. Six sociocultural factors had direct paths to quality of prenatal care: amount of insurance, delay in telling others about the pregnancy, attitudes toward health professionals, month of gestation in which the pregnancy was suspected, perception of the importance of prenatal care, and initial attitude toward the pregnancy. Together, these factors accounted for 64% of the variance in the quality of prenatal care received. Four variables had direct paths to birth weight: month in which the pregnancy was suspected, quality of prenatal care, hypertension, and substance abuse, which together accounted for 13% of the variance in birth weight. The key findings were the relative impact that the quality of prenatal care, especially the source of care, had on birth weight, and the potential for improving birth outcomes by addressing the negative effects of underlying social factors. PMID- 2314780 TI - Head-to-cervix forces and their relationship to the outcome of labor. AB - The force (as distinct from pressure) between the fetal head and the maternal cervix during labor was measured for the first time in an attempt to improve the intrapartum prediction of progress in labor. The 50th percentile of the variables active pressure and active force and the mean uterine activity integral were compared with the cervical dilatation rate and delivery mode in 31 women. The 50th percentile of active force had the highest correlation with the cervical dilatation rate (r = 0.54) (50th percentile of active pressure, r = 0.43; mean uterine activity integral, r = 0.40). The 50th percentile of active force was significantly higher in women who achieved a vaginal delivery (mean +/- SD 45 +/- 21.2 g wt) than in those who underwent cesarean delivery for failure to progress (16.5 +/- 9 g wt). The 50th percentile of active force discriminated among modes of delivery as effectively as did the cervical dilatation rate. These results support the hypothesis that head-to-cervix force measurements may have clinical value in the management of labor. PMID- 2314781 TI - Plasma fibronectin concentrations during normal term labor. AB - We measured plasma concentrations of fibronectin in 30 normal parturients in early labor and at the time of delivery, using a rapid immunoturbidimetric assay. We compared these values with those of 30 healthy nonpregnant control women. The mean plasma concentrations of fibronectin in women in early labor and at delivery were 400 +/- 104 and 410 +/- 147 micrograms/mL, respectively (not significant). Both of these values were higher than the mean fibronectin concentration in controls, 283 +/- 81 micrograms/mL (P less than .0001). We conclude that plasma concentrations of fibronectin are higher in pregnant women than in nonpregnant controls and that they remain relatively constant during uncomplicated term labor. PMID- 2314782 TI - Histologic chorioamnionitis and preterm delivery in different patient populations. AB - The placentas of 1843 deliveries were examined for the presence of histologic chorioamnionitis, which was classified as mild, moderate, or severe. Chorioamnionitis was present in 7.5% of patients who underwent cesarean before labor and in 18 and 32% of those delivering at term and preterm, respectively. Chorioamnionitis was severe in 74% of preterm but in only 15% of term deliveries. Premature rupture of membranes (PROM) was more frequent with preterm than with term delivery, with chorioamnionitis present in 42 and 15% of patients, respectively. Although chorioamnionitis was equally frequent in women with intact membranes delivering preterm and term, chorioamnionitis was severe in 63% of preterm and 14% of term deliveries (P less than .001). The frequency and severity of chorioamnionitis were related inversely to gestational age at preterm birth. Preterm delivery was more frequent in black than in white patients (19 versus 9%) and in indigent clinic versus private patients (13 versus 7.5%). However, there was no significant difference in frequency and severity of chorioamnionitis between black and white or between indigent clinic and private patients who delivered preterm. Among term births, chorioamnionitis was more often severe in black than in white patients. Chorioamnionitis in term deliveries was more frequent in clinic than in private patients; however, this was not true when only severe chorioamnionitis was considered. There were no differences in PROM between these patient populations. Thus, higher preterm birth rates in black and indigent clinic populations are not due to the more frequent occurrence of chorioamnionitis. PMID- 2314783 TI - Bacteriologic findings of post-cesarean endometritis in adolescents. AB - Two hundred four post-cesarean adolescents were compared with 751 adults to determine whether age was a risk factor for endometritis. Adolescents had an infection rate of 23%, compared with 11% for controls (P less than .001). Length of labor, duration of ruptured membranes, and the use of an internal monitor were noted to be risk factors for endometritis in adults, but not in adolescents. Endometrial aspirates from adolescents exhibited significantly higher isolation rates of Chlamydia trachomatis (21 versus 6%, P less than .05) and Gardnerella vaginalis (32 versus 9%, P less than .005) than did those from adults. Antepartum isolation of these organisms in teenagers may help to identify those at risk for postpartum endometritis. PMID- 2314784 TI - Megestrol acetate for treatment of endometriosis. AB - Between 1977-1989, 29 women with symptomatic endometriosis were treated with megestrol acetate by the Johns Hopkins Division of Reproductive Endocrinology. All had previously received one or more alternative medical treatments for endometriosis, in each case discontinued because of poor response or development of unacceptable side effects. Treatment consisted of a daily dose of 40 mg megestrol acetate orally for up to 24 months. Disease-related symptoms (dysmenorrhea, noncyclic pelvic pain, and dyspareunia) were relieved in 86% of the subjects treated with an adequate course of therapy. Side effects were fairly well tolerated, although eight women discontinued treatment within 2 months and two others stopped the drug by 4 months. These preliminary findings suggest that megestrol acetate may be an effective treatment for patients with endometriosis, even those who have been unresponsive to other modes of therapy. PMID- 2314785 TI - Seroprevalence and epidemiologic correlates of human immunodeficiency virus infection in women with acute pelvic inflammatory disease. AB - As the number of women with acquired immunodeficiency syndrome (AIDS) continues to rise in the United States, it becomes important to target preventive interventions as effectively as possible toward those groups at highest risk of acquiring human immunodeficiency virus (HIV) infection. We analyzed the prevalence of serum antibody to HIV in 333 women admitted to the Gynecology Service at San Francisco General Hospital with acute pelvic inflammatory disease in the years 1985-1988. The proportion of women with HIV infection in our sample rose incrementally over this 4-year period, from 0 to 6.7%. A history of intravenous (IV) drug use conferred a 23-fold risk of HIV seropositivity. In contrast, markers of the level of sexual activity did not correlate significantly with the presence of HIV infection, although the power to detect such an association was limited by the small sample size. An intensification of educational efforts directed at IV drug-using women in San Francisco is necessary to prevent further increases in the rate of HIV infection and further spread into the heterosexual population. PMID- 2314786 TI - Stress urinary incontinence: effect of pelvic muscle exercise. AB - Twenty women with stress urinary incontinence diagnosed by urodynamic testing participated in a 6-week pelvic muscle exercise program. The aim of the study was to evaluate the effectiveness of the exercise program, with or without an intravaginal balloon, on urinary leakage as determined by a 30-minute and a 24 hour pad test. Relative strength of the pelvic muscles was evaluated using an intravaginal device that measures the pressure generated during a muscle contraction. After completion of the exercise program, 18 of the 20 subjects had an increase in strength of the pelvic floor muscles, as demonstrated by increased intravaginal pressure or a decrease in urinary loss on the 24-hour pad test. The use of an intravaginal balloon did not improve performance of the pelvic muscles or decrease urinary loss as compared with the subjects who exercised without an intravaginal balloon. Twelve months after the completion of the exercise program, 19 of the participants responded to a questionnaire about their urinary loss and performance of pelvic muscle exercises. None of the subjects stated that her urinary loss was worse, three had undergone surgical intervention, and ten had not continued to exercise. Seven subjects still exercised, with subjective improvement of urinary loss. It appears that pelvic muscle exercises may be successful in improving the condition of stress urinary incontinence; however, half of the subjects did not continue to exercise independently. PMID- 2314787 TI - Functional ovarian cysts in patients cured of ovarian neoplasms. AB - Twenty-seven patients with ovarian cancer underwent unilateral salpingo oophorectomy and were followed for 12-215 months (mean 80) after completion of therapy. Of these, nine patients who received pelvic irradiation subsequently developed ovarian failure. Of the remaining 18 patients who maintained ovarian function, 13 (72%) developed a functional ovarian cyst during the follow-up period. Of these 13 patients, eight were observed until the functional cyst regressed, four were treated with oral contraceptives (OCs) to suppress ovarian function, and one underwent oophorectomy for a large corpus luteum cyst. We recommend that OC pills be considered for suppression of ovarian function in postmenarcheal girls after completion of therapy for ovarian neoplasms. Routine use of OCs may simplify the follow-up of these patients by preventing the formation of functional ovarian cysts. In postmenarcheal patients not treated with OCs, the finding of a unilocular ovarian cyst should be considered to represent a functional cyst, and a trial of OCs for 3 months may result in spontaneous regression. Persistent cysts must be operatively removed. PMID- 2314788 TI - Controlled evaluation of implementing the Cytobrush technique to improve Papanicolaou smear quality. AB - The effect of introducing the Cytobrush Cell Collector for endocervical sampling on the quality of Papanicolaou smears was evaluated using a quasi-experimental design. Baseline evaluation of the Ayre spatula-cotton swab method in two patient groups showed that only 61.8-61.9% of smears contained endocervical cells. Replacing the cotton swab with the Cytobrush in the intervention group improved endocervical cell yields to 82.0% (P less than .001). This improvement was not due to group differences in patient factors previously related to endocervical cell yields, eg, parity, use of oral contraceptives, pregnancy, previous cervical procedures, and menopausal status. An increase in the proportion of Papanicolaou smears showing dysplasia or cancer (class III or higher) was associated with use of the Cytobrush (P less than .05). Subsequent introduction of the Cytobrush to the control group resulted in a similar significant improvement in cell yields to 82.5% (P less than .001). Greater use of methods such as the Cytobrush Cell Collector in the primary care setting can improve cervical cancer screening by reducing the number of false-negative Papanicolaou smears resulting from inadequate endocervical cell sampling. PMID- 2314789 TI - Medical professional liability and obstetric care: the Institute of Medicine report and recommendations. PMID- 2314790 TI - Let's get rid of the term "Braxton Hicks contractions". AB - The early detection of preterm labor and the prevention of preterm birth require special attention to early subtle signs and symptoms of preterm labor. The concept of "Braxton Hicks contractions" may negate these early signs and symptoms by falsely reassuring patients, thus encouraging them not to seek medical care promptly. PMID- 2314791 TI - The demise of vaginal operative obstetrics: a suggested plan for its revival. AB - Predictions made more than a quarter of a century ago regarding excessive use of cesarean delivery for cases of dystocia have been realized. Breech presentation, correctable dystocia, and twin gestation are increasingly being delivered by the abdominal route. Recent studies have shown that neonatal morbidity is not inherently improved by cesarean birth, and in fact have reported comparable results with vaginal operative procedures in properly selected and managed cases. Pressure to control the cesarean birth rate is now being exerted by consumer groups, professional groups, and governmental agencies. The reintroduction of vaginal operative procedures to modern obstetrics would help reduce the cesarean birth rate. However, major changes in the medical liability system, medical education and training, and the method of certifying obstetricians will be required before vaginal operative obstetrics becomes a serious alternative to cesarean delivery. Without these changes, I believe there is little hope of reversing the trend toward cesarean birth. PMID- 2314792 TI - Breast-feeding and the potential for human immunodeficiency virus transmission. AB - There is evidence to suggest that the human immunodeficiency virus (HIV) can be transmitted from mothers to their uninfected offspring via infected breast milk. The quantitative risk of transmission by this route is unknown. We must urge all individuals at risk for HIV infection to be tested. In the United States, it is recommended that women who are known to be HIV-positive be discouraged from breast-feeding. In certain regions of the United States, such as high-risk areas of New York City, HIV infection may be present in more than 3% of reproductive age women, most of whom do not know they are infected. Women who either live in areas of the United States in which acquired immunodeficiency syndrome (AIDS) is endemic or are living in other parts of the country and are at high risk for AIDS, yet refuse to be tested, should be counseled regarding the potential for transmission of the virus to uninfected offspring via breast-feeding. PMID- 2314793 TI - Education on breast disease in an obstetrics and gynecology training program: a multidisciplinary approach. AB - Breast cancer affects one in ten women during their lifetime. Recognizing the importance of early detection in the prognosis of this condition, the American Board of Obstetrics and Gynecology has stated guidelines encouraging breast disease education in obstetrics and gynecology training programs. To fulfill this academic responsibility, we have organized a multidisciplinary Breast Disease Detection and Treatment Clinic where patients with abnormal mammograms or any breast-related complaints are evaluated and managed. In cooperation with the radiology department and general surgery service, a mammogram review conference has been instituted. Abnormal mammograms are reviewed with a radiologist. Our activities have been coordinated such that a general surgery staff member and resident are present during the breast clinic hours to review mammograms and to examine the patients with the gynecologist, providing immediate consultation. Needle aspiration of breast cysts, repeat imaging studies, and general surgery referrals for breast biopsies are performed as indicated. The patient receives integrated care of her breast problem in one visit, and our residents gain the experience of diagnosing and managing breast problems which, before establishment of this clinic, were referred to the general surgery department. This multidisciplinary approach developed in our institution helps us provide the most efficient care to our patients, while providing our residents with integrated teaching and training concerning the diagnosis and management of breast disease. PMID- 2314794 TI - The use of modified Martius graft as an adjunctive technique in vesicovaginal and rectovaginal fistula repair. AB - The use of the Martius graft, a labial fibro-fatty tissue graft, is described as an adjunctive technique in the repair of 37 complex fistulas in 35 patients. The graft was used to repair three groups of patients with non-radiation-induced vesicovaginal fistulas: 12 patients with large (greater than 4 cm) obstetric fistulas, six patients with obstetric fistulas that caused urethral sloughing, and six patients with recurrent obstetric or post-hysterectomy fistulas. Five other patients had radiation-induced fistulas, and six others had rectovaginal fistulas. The overall success rate was 86.5%. Anatomical studies undertaken of the graft in a cadaver demonstrated that it is composed of fibroadipose tissue from the labium majus, and not from the bulbocavernosus muscle. It receives its blood supply anteriorly from the external pudendal artery and posteriorly from the internal pudendal artery. These vessels form a plexus within the graft. The prominence of fibrous tissue in this fibroadipose tissue arises from a superficial tunic of fibrous tissue similar to the tunica dartos in the male, as well as from the considerable fibrous septa within the adipose tissue itself. Although the labial graft used today differs from that originally described by Heinrich Martius, it remains a safe, simple, and helpful technique in difficult fistula repairs. PMID- 2314795 TI - Vaginal birth after cesarean: is suspected fetal macrosomia a contraindication? PMID- 2314796 TI - Current perspectives in the management of the menopausal and postmenopausal patient: introduction. PMID- 2314797 TI - Enhancing patient compliance with hormone replacement therapy at menopause. AB - Physicians who prescribe hormone replacement therapy for menopausal women should explain the purpose, risks, and side effects of the treatment. This enhances compliance and discourages patients from discontinuing therapy because of fears of cancer or misconceptions about hormone replacement therapy. The physician should explain that the risk of endometrial cancer is virtually eliminated (reduced to that of a normal woman or a woman not receiving therapy) by the addition of progestogen to estrogen regimens, and that when this cancer does occur, it is usually diagnosed and treated early. Recent studies have not conclusively shown a significant effect of progestogen on lipid profiles relevant to cardiovascular disease. Hormone replacement therapy does not appear to be associated with an increased risk of breast cancer. Nuisance side effects (such as edema and breast tenderness) can be better tolerated if the physician prepares the patient, offers a solution, and helps to put the problem in perspective. Other measures, such as providing written information and avoiding unnecessary biopsies, also enhance compliance. PMID- 2314798 TI - Competent to judge noise at work? PMID- 2314799 TI - Audiometry: why and how. PMID- 2314800 TI - Working alone on dark evenings--a hazard for researchers. PMID- 2314801 TI - Is HSE making itself heard? Health and Safety Executive. PMID- 2314802 TI - 'Bad dose of the flu'. PMID- 2314803 TI - Contractors' employees. Who is liable? PMID- 2314805 TI - Formation of an independent professional organisation for OH and safety nurses. PMID- 2314804 TI - Are we occupational health nurses or OH practitioners? PMID- 2314806 TI - The future of occupational health practice. PMID- 2314807 TI - Counseling the HIV-test subject ... AIDS. PMID- 2314809 TI - Making the grade, a report card on American youth. PMID- 2314808 TI - Building doctor-staff rapport. PMID- 2314810 TI - Travails of Ohio's grim reapers. PMID- 2314811 TI - How to be a sports medicine physician: the old tape and go. PMID- 2314812 TI - Advances in pediatrics. PMID- 2314813 TI - Reviewing and checking medical records. PMID- 2314814 TI - Electra complex. PMID- 2314815 TI - Cholesterol crusade continues. PMID- 2314816 TI - Circumcision--another look. PMID- 2314817 TI - Grief in children studied. PMID- 2314818 TI - Over 40 and "the pill". PMID- 2314819 TI - Schizophrenia drug approved. PMID- 2314820 TI - Elliptinium acetate in metastatic breast cancer--a phase II study. AB - Thirty-five patients with metastatic breast cancer who had received one or two prior chemotherapeutic regimens were treated with elliptinium acetate at a dose of 80 mg/m2 for 3 days every 3 weeks. Of the 33 patients evaluable for response, 1 patient achieved complete remission, 4 achieved partial responses (15% overall objective response with 95% confidence interval of 5-32%), and 6 achieved minor response. Toxicity of the treatment was xerostomia, diarrhea, and nausea and vomiting. The drug was not myelosuppressive. Three patients showed evidence of elliptinium antibody, and treatment was discontinued. No episodes of hemolysis were observed. Elliptinium acetate showed modest antitumor activity in previously treated patients with metastatic breast cancer. PMID- 2314821 TI - Doxorubicin and etoposide in the treatment of advanced measurable breast cancer. AB - Nineteen evaluable patients with advanced breast cancer were treated with a combination of doxorubicin and etoposide. Patients had measurable disease, received only mild pretreatment and most had good general conditions at start of therapy. Strict criteria for dose adjustments according to nadir counts were applied. A 42% response rate was obtained. Toxicity was mild and treatment well tolerated. Doxorubicin-etoposide is an active regimen for patients with breast cancer and warrants further testing in a larger patient population with less stringent criteria for evaluation and treatment monitoring. PMID- 2314822 TI - Cisplatin-containing versus cisplatin-free adjuvant chemotherapy in ovarian carcinoma. Results after second-look laparotomy. AB - In 1980, second-look laparotomy was introduced simultaneously into the treatment regimen for ovarian carcinoma at the two main referral centers of northern Spain. First-line chemotherapy after initial surgery was, however, different at both hospitals. At one of them (Bilbao), a combination involving the use of cisplatin was employed (cyclophosphamide 600 mg/m2, Adriamycin 45 mg/m2, and cisplatin 80 mg/m2 i.v. on day 1), whereas the patients of the other hospital were treated mainly with single-agent chemotherapy (melphalan 0.2 mg/kg p.o. on days 1-5) and never with a cisplatin combination as first-line therapy in any case. In all, 92 patients (42 stage I, 14 stage II, 33 stage III, and 3 stage IV) could be treated during the study period with optimal surgery (complete tumor excision or largest residual tumor less than 2 cm in diameter). This was followed by adjuvant chemotherapy for 12-18 months in all cases, except for 18 patients with a stage Ia borderline or G1 tumor. The latter were merely kept under observation until their second-look laparotomy after 1 year of negative follow-up. All of the 74 patients who received adjuvant chemotherapy, of whom 36 with cisplatin and 38 without, were clinically disease free after at least twelve courses of treatment and had a second-look laparotomy performed. This was positive in 33.3% of the cases after cisplatin-containing therapy and in 26.3% of the cases after cisplatin-free therapy. This difference is not statistically significant. The mean follow-up period after negative second-look was 34 months. The long-term results of both patient groups were comparable as far as rate of positive second look laparotomies and survival rate, overall and stage for stage are concerned. The use of cisplatin did not result in any significant therapeutic improvement. It was uniformly bad tolerated by the patients and carried higher cost, since all patients had to be hospitalized for treatment. PMID- 2314823 TI - Mitoxantrone, etoposide and cytarabine in the treatment of acute nonlymphocytic leukemia. AB - In a phase I/II study mitoxantrone and etoposide, in combination with cytarabine, were given to 26 patients with refractory, relapsed, and previously untreated acute nonlymphocytic leukemia. Therapy consisted of mitoxantrone 12 mg/m2/day for 3 days, etoposide 100 mg/m2/day and cytarabine 1 g/m2 twice a day for 5 days. A total of 14 complete remissions (CR, 54%) were noted. Among refractory patients 5 of 10 achieved a CR as compared to 5 of 6 in the previously untreated group. A favorable response was also seen in patients with late relapse off treatment (3/4 CR) while patients relapsing on therapy did worse (1/6 CR). The results suggest a high antileukemic activity and a moderate toxicity for this drug combination. PMID- 2314824 TI - Evaluation of local control, survival and pattern of failure with radiotherapy in cancer of the tongue. AB - 105 patients with cancer of the tongue were treated with radical radiotherapy in 1982 at the Regional Cancer Centre, Trivandrum, India. The overall local control rate was 55% and the 3-year actuarial disease-free survival was 36% with radiotherapy. The analysis revealed a close correlation between stage of the disease and local control as well as survival. 45% of the patients with clinically positive cervical nodes had their disease controlled by radiotherapy. Since the best results were obtained with early disease, the need for clinical downstaging by early detection is stressed. PMID- 2314825 TI - Advanced colon cancer: staging and prognosis by CEA test. AB - The carcinoembryonic antigen (CEA) test was studied in 54 patients with advanced stages of colon cancer which was treated with high doses of folinic acid + fluorouracil. The CEA test correlates evaluated included: prognostic value, performance status, metastatic pattern, histologic grading, predictive value for response to chemotherapy, and value differences in cases with partial response to therapy. CEA levels less than 5 ng/ml corresponded to a greater survival time than did levels greater than 5 ng/ml. A correlation of CEA with performance status and with metastatic pattern was demonstrated. A progressive increase in average CEA values corresponded to increases in neoplastic mass. Although CEA levels were not found to be an index for predicting the response to chemotherapy, there was a significant different between pre- and posttreatment levels for partial response. The results suggest that CEA offers an additional criterion for evaluating the response of colon cancer to chemotherapy and it also has a role in the staging of advanced disease. PMID- 2314826 TI - Dose and schedule effects of cisplatin on the related acute iron changes. AB - To investigate the relationships between cisplatin and the related erythropoiesis impairment, 14 patients receiving very-high-dose cisplatin (40 mg/m2/day for 5 days) and 17 patients receiving standard-high-dose cisplatin (either a single dose of 100 or 20 mg/m2/day for 5 days) entered this study. Iron, ferritin, hemoglobin, and reticulocyte levels were evaluated before, 4 and 6 days after each course of cisplatin. A complete blood count was obtained weekly. During the 1st week after chemotherapy, iron and ferritin levels significantly increased, and the reticulocyte count decreased. Iron changes depend on the cisplatin dose, but are not related to the different schedules employed. The severity of subacute anemia was found to be dependent on the cisplatin dose administered and on hemoglobin pretreatment levels. Some relationships between cisplatin, iron changes, and the subacute hemoglobin decrease are described. PMID- 2314827 TI - Murine monoclonal antibodies to human pancreatic cancer: specificity and sensitivity. AB - Pancreatic carcinoma (n = 7), pancreatitis tissue (n = 4), normal pancreas tissue (n = 5), colonic adenocarcinoma (n = 4) and in vitro human pancreatic cancer cell lines (n = 6) were studied with the murine monoclonal antibodies (MAbs) 3DS2A, AR1-28, AR2-20, Ca19-9 and CA17-1A to determine their immunohistologic specificity and sensitivity for use as radiolabeled diagnostic imaging agents. Using the avidinbiotin-immunoperoxidase staining technique, MAbs 3DS2A and AR1-28 stained 86 and 100% of pancreatic cancer specimens, respectively. MAbs 3DS2A and AR1-28 are suitable agents for use as radiolabeled diagnostic imaging agents in patients with pancreatic cancer. PMID- 2314828 TI - Application of the immunohistochemical method as a predictive assay in radiotherapy of squamous cell carcinoma of oropharynx and hypopharynx. AB - We analyzed various subsets of lymphocytes infiltrated into cancer tissues from 15 patients (10 cases of oropharyngeal cancer and 5 of hypopharyngeal cancer) before treatment and after irradiation with approximately 10 Gy (1,000 rad) and 30 Gy by the method of biotin-avidin-horseradish peroxidase using mouse monoclonal antibodies. The infiltration was graded (marked) to - (none). In 3 cases, tumor-infiltrating lymphocytes were remarkably increased at the delivery of a small dose of irradiation (approx. 10 Gy): 2 of them showed remarkable radiosensitivity, and the lymphocyte subpopulation of the cancer tissue was mainly composed of Leu-3a + 3b-positive and Leu-8-negative lymphocytes (helper inducer T lymphocytes or delayed-type hypersensitivity cells). On the other hand, the third one proved to be rather radioresistant, and the lymphocyte subpopulation was mainly composed of Leu-14-positive lymphocytes (B lymphocytes). These findings indicate that the analysis of the lymphocyte subpopulation infiltrating into cancer tissues at the delivery of small doses of irradiation is applicable as a predictive assay in radiotherapy of squamous cell carcinoma of the oropharynx and hypopharynx. PMID- 2314829 TI - In vivo response of mitoxantrone and doxorubicin with dipyrone in parental and doxorubicin-resistant P388 leukemia. AB - The efficacy of dipyrone to modulate antitumor activity of mitoxantrone (MTN) and doxorubicin (DOX) was studied in vivo in mice bearing P388 murine lymphocytic leukemia sensitive (P388/S) and resistant P388/DOX) to DOX. P388/DOX-bearing mice demonstrated marginally higher sensitivity to dipyrone at 200 mg/kg when compared to P388/S-bearing mice. However, dipyrone could significantly enhance the antitumor activity of MTN and DOX in both P388/S and P388/DOX-tumor-bearing mice. MTN was cross-resistant to P388/DOX. PMID- 2314830 TI - Establishment and characterization of a human ovarian serous cystadenocarcinoma cell line that produces the tumor markers CA-125 and tissue polypeptide antigen. AB - A cultured cell line (SHIN-3) derived from a human ovarian serous cystadenocarcinoma which consistently produces two tumor markers, CA-125 and tissue polypeptide antigen (TPA) was established. After 1 week of culture of 1 x 10(5) cells, high levels of tumor marker were observed (the total CA-125 release was 1,500 U and the total TPA release was 37.5 U). Expression of CA-125 and TPA was also demonstrated in cultured cells immunohistochemically. The volume of CA 125 release per cell was highest just before the start of the logarithmic growth phase. TPA production was increased in the logarithmic growth phase, but its relationship to the total number of cells was not clear. PMID- 2314831 TI - Phase II study of pirarubicin (THP-adriamycin) in metastatic breast cancer patients. AB - Fourteen patients with metastatic breast cancer previously treated with one chemotherapy regimen received Pirarubicin at a dose of 70 mg/m2 at 3-week intervals. In 7 patients the dose had to be reduced, in 1 patient to 40 mg/m2 and in 6 patients to 50-60 mg/m2. There were 1 complete and 2 partial remissions. These objective responses were observed in soft tissue, lung and pleural areas and lasted 1+; 4+ and 5+ months. Grade 3 and 4 leukopenia was found in 42%, grade 3 thrombocytopenia in 2%, grade 3 nausea/vomiting in 29% of the cycles. Grade 1 and 2 alopecia occurred in 64% of the patients, the remaining 36% of the patients did not suffer from any alopecia. No cardiotoxic side effects were observed in 13 patients. In 1 patient with severe coronary heart disease extrasystoles and reduction in left ventricular ejection fraction occurred. Pirarubicin has antitumor activity in previously treated metastatic breast cancer patients. PMID- 2314832 TI - The pathology of posterior amorphous corneal dystrophy. AB - The youngest affected member of a family with a five-generation history of posterior amorphous corneal dystrophy underwent penetrating keratoplasty. The corneal button was studied by light and electron microscopy, representing the first pathologic description of this condition. Light microscopy demonstrated fracturing of the most posterior collagen layers of the stroma and focal attenuation of endothelial cells. Electron microscopy showed the collagen fibers in the most posterior stromal lamellae to be disorganized. Descemet's layer was interrupted by a band of collagen fibers resembling stroma, and there was loss of endothelial cells. These findings suggest a developmental abnormality in the formation of the posterior stroma and Descemet's membrane in posterior amorphous corneal dystrophy. PMID- 2314833 TI - Anterior segment evaluation of infants with retinopathy of prematurity. AB - To understand the mechanisms of glaucoma in retinopathy of prematurity (ROP), anterior segment evaluation is essential. The authors prospectively examined the anterior segment of 27 eyes of 17 premature infants with stages IV and V ROP. Twenty-six eyes received no previous surgery or treatment. Schiotz and applanation tonometry were performed. Structural evaluation of each anterior segment was conducted by biomicroscopy and Koeppe gonioscopy. In the 26 eyes, angle closure of greater than 180 degrees was noted in 3 (12%). The authors noted prominent Schwalbe's line in 4 eyes (15%), high iris convexity in 15 (58%), hypopigmentation of the iris root in 19 (73%), translucent matrix in the angles ("Barkan's-type" membrane) in 18 (69%), posterior synechiae in 16 (62%), visible iris or angle vessels in 12 (46%), and pigment clumping in the angle recess in 12 (46%). This study identified structural abnormalities in the anterior segment of ROP infants, including pathologic changes and anatomic features that could have a developmental origin. PMID- 2314834 TI - Recognition and repair of the "lost" rectus muscle. A report of 25 cases. AB - Twenty-five consecutive cases of lost muscle over a 10-year period are presented with regard to etiology, clinical presentation, operative findings, and treatment results. All patients showed a large-angle strabismus and all muscles had marked limitation of excursion in its field of action. This complication of ocular surgery or trauma, unlike the slipped muscle which has its empty capsule attached to the sclera, is characterized by the absence of any attachment of the muscle or its capsule to the sclera. Eleven of the 25 muscles were retrievable largely because of attachments through intermuscular septum to adjacent oblique muscles. The remaining 14 muscles were considered irretrievable, and these patients underwent a muscle transposition procedure. The clinical features and surgical repair of the lost muscle are described and compared with those of the slipped muscle. PMID- 2314835 TI - Training ophthalmology residents to treat patients with vision loss. Results of a demonstration program. AB - Ophthalmology residents attended a day-long training program designed to teach them about the rehabilitation needs of visually impaired and blind patients. A pretest measuring the participants' knowledge of rehabilitation services and their rehabilitation-oriented activities was administered before the training program and a posttest measuring the same items was administered 6 months after the program. Several of the rehabilitation-oriented measures that participants themselves take with visually impaired and blind patients increased substantially during the 6-month period as did their knowledge of rehabilitation services available in the community. The referrals made for these rehabilitation services and the participants' interactions with allied health professionals who serve visually impaired and blind patients increased only slightly. These findings suggest the need to institutionalize training for residents in the topic of rehabilitation and to allocate time within their schedules for making referrals and working cooperatively with allied health professionals. PMID- 2314836 TI - Visual loss caused by rapidly progressive intracranial meningiomas during pregnancy. AB - Three cases of intracranial meningiomas occurring in young pregnant women are presented. The typical growth pattern of these tumors is slow, producing insidious and chronic visual disturbances. In contrast, during pregnancy meningiomas may follow a rapidly progressive course, producing dramatic and relatively acute visual loss. This accelerated growth pattern is probably mediated by hormone receptors in these tumors. Nausea, vomiting, and other symptoms caused by the tumor may be attributed to pregnancy, delaying the diagnosis. Symptoms may abate spontaneously after delivery only to recur with greater rapidity and severity during subsequent pregnancies. Hormone-responsive intracranial meningiomas must be considered in the differential diagnosis of visual disturbances during pregnancy. Close cooperation between the ophthalmologist, neurosurgeon, obstetrician, and neonatologist is essential for an optimal outcome. Although surgical excision remains the treatment of choice, hormonal therapy may be valuable in treating unresectable or partially resectable meningiomas. PMID- 2314837 TI - Role of cryotherapy in treating sebaceous carcinoma of the eyelid. PMID- 2314838 TI - Orbitofrontal cholesterol granuloma. AB - Cholesterol granuloma of the orbital bones is a rare but readily recognizable clinical and radiologic entity usually affecting men. Twenty-seven patients are reported, and in all except one, the frontal bone in the region of the lacrimal fossa was involved. These lesions produced an area of osteolysis in the frontal bone with expansion into the extraperiosteal space of the lacrimal fossa, causing fullness of the upper lid and proptosis. The granuloma always remained extraperiosteal and was composed of a granulomatous reaction surrounding cholesterol crystals and altered blood. It is postulated that cholesterol granuloma occurs because of hemorrhage into the diploe of the bone. Extraperiosteal surgical removal cured all patients. Some previous reports have failed to identify the true nature of this lesion and confused its nomenclature. PMID- 2314839 TI - Functional scoring of the field of binocular single vision. AB - Fifty-one patients with diplopia were investigated prospectively to assess the correlation between their subjective impression of disability from diplopia and an objective measurement obtained using a method of assessing the field of binocular single vision (BSV). The objective score generally exceeded the patient's own assessment and the scoring method has been modified to improve the correlation. PMID- 2314840 TI - Flicker sensitivity in treated ocular hypertension. AB - Reductions in flicker sensitivity in ocular hypertension are thought to precede manifest glaucomatous damage, but the proportion of patients with ocular hypertension reported to have losses in flicker sensitivity (50-90%) is far out of step with the proportion of ocular hypertensive patients in whom clinically defined glaucoma will develop (5-30%). The authors examined the possibility that the flicker losses in some of these patients represent not early glaucomatous damage, but instead a transient influence of raised intraocular pressure (IOP) on an otherwise normal eye. Temporal contrast sensitivity was measured in 26 patients with ocular hypertension and in 22 patients with primary open-angle glaucoma (POAG) before and after hypotensive treatment (timolol). Compared with normotensive controls, all POAG patients exhibited sensitivity losses before treatment which remained unchanged after treatment. The ocular hypertensive patients were divided into three groups, which may reflect differing risks of glaucoma conversion. Group I patients (8/26) had normal flicker sensitivity, and thus appear to be resistant to high IOP. Group II patients (9/26) showed initial losses which disappeared with lowered IOP. They probably have not yet suffered damage but appear to be sensitive to high IOP. Group III patients (9/26) had losses that persisted despite lowered IOPs. The similarity of their response to that of the POAGs suggests that group III patients have already suffered early glaucomatous damage. PMID- 2314841 TI - Orbital toxicity from insecticides. PMID- 2314842 TI - Effect of patient experience on the results of automated perimetry in glaucoma suspect patients. AB - The first four Octopus-automated visual field examinations of 29 patients with elevated intraocular pressure but apparently normal optic discs and Goldmann visual fields were studied for the presence of a learning effect on the visual field parameters of mean sensitivity, number of disturbed test locations, total field loss, and short-term fluctuation. A learning effect, if present, would manifest itself as an improvement in the visual field as patients become more experienced with the test. There was no apparent effect of patient experience on the mean sensitivity of the whole visual fields or the mean sensitivity of the test locations within 20 degrees of fixation. There was a significant (P = 0.012) increase in mean sensitivity for the test locations outside 20 degrees of fixation. There were significant (P less than 0.01) improvements in short-term fluctuation, total loss, and number of disturbed points between the first and second visual field examinations. The results indicated that there was a learning effect between the first and second automated visual field in glaucoma suspect patients who had previous experience with manual perimetry. It was not, however, very large in most patients and seems to be present in the peripheral portions of the visual field only. In most cases, it was not necessary to obtain more than two "baseline" examinations unless a patient demonstrated unusually high short term fluctuation or had visual field defects inconsistent with the remainder of their clinical examination. PMID- 2314843 TI - Investigations into a vascular etiology for low-tension glaucoma. AB - Increased intraocular pressure is accepted as a primary etiologic factor for the atrophy of the optic nerve head and visual field defects of high-tension glaucoma. Other factors must be present to explain these findings in low-tension glaucoma. One of the current theories is that low-tension glaucoma is the result of decreased optic nerve perfusion on the basis of vascular disease or other factors such as altered blood viscosity. This study compared the non-invasive vascular profiles, coagulation tests, and rheological profiles of 46 consecutive cases of low-tension glaucoma with 69 similarly unselected cases of high-tension glaucoma and 47 age-matched controls. Despite the multifactorial approach and the use of previously validated objective tests, no significant group differences were detected with any of the above investigations. If vascular disease is important in the etiology of low-tension glaucoma, then it must be localized or vasospastic since this study does not support the concept of a generalized vascular etiology, either of an atheromatous or hyperviscous nature, for the genesis of low-tension glaucoma. PMID- 2314844 TI - Clearing of bilirubin from donor corneas. PMID- 2314845 TI - Management of encapsulated filtration blebs. AB - Increased intraocular pressure (IOP) in encapsulated filtration blebs was evaluated in 49 eyes of 49 patients followed for 6 to 48 months (mean +/- standard deviation, 19.7 +/- 12.6 months). Intraocular pressure increased from 10.2 +/- 7.5 mmHg at 1 week postfiltration surgery to a peak of 26.1 +/- 10.7 mmHg at 3 weeks postoperatively and then decreased to 16.2 +/- 5.0 mmHg at 16 weeks and remained stable through the follow-up period. Thirty-nine eyes had a final IOP of 19 mmHg or less; 35 eyes required medical therapy alone (antiglaucoma drops, oral carbonic anhydrase inhibitors, and/or digital massage) with a final IOP of 14.1 +/- 3.8 mmHg; and 14 eyes required surgical reintervention for medically uncontrolled IOP elevation, and five of these eyes required two or more surgical reoperative procedures. Vigorous medical therapy, including glaucoma medications, topical steroids, and digital massage, is particularly important for encapsulated blebs during the first 2 months after surgery. After this period, IOP decreases and often remains sufficiently reduced to avoid further surgical intervention. PMID- 2314846 TI - Alzheimer's disease, optic neuropathy, and selective ganglion cell damage. PMID- 2314847 TI - Mid-term effects of neodymium: YAG transscleral cyclocoagulation in glaucoma. AB - Neodymium: YAG (Nd:YAG) transscleral cyclocoagulation successfully lowers intraocular pressure (IOP) over the short term in animals and humans. Twenty eight eyes with uncontrolled glaucoma were prospectively followed over a mean period of 21.9 months. Mean pretreatment IOP was 47.5 mmHg. Mean posttreatment IOP was 19.9 mmHg (P less than 0.005). Mean (+/- standard deviation) number of treatments was 1.86 (+/- 1.11) Mean number of drugs used before and after treatment was 3.28 and 2.48, respectively (P less than 0.01). A total of 10.7% eyes went phthisical. Thirty percent of eyes with vision and good IOP control (i.e., less than 21 mmHg) lost some vision after the procedure. Neodymium:YAG transscleral cyclocoagulation appears to be an effective method of controlling IOP over the mid-term, but is associated with significant complications. PMID- 2314848 TI - Comparison of specular microscopy and examination of aspirate in phacolytic glaucoma. AB - Although phacolytic glaucoma is well known and the clinical picture is well recognized, the nature of the polychromatic hyperrefringent granules is less well understood. A series of five cases was examined by specular microscopy, and the anterior chamber aspirate obtained at operation was subsequently examined by direct microscopy of the wet aspirate. Direct microscopy showed that the macrophages identified histologically in the aspirate corresponded to regular round cells about three times the size of an erythrocyte seen in the relief mode of specular microscopy. This finding aided in the interpretation of cellular deposits seen on specular microscopy. One hyperrefringent granule was seen on the posterior endothelium on specular microscopy, and results of subsequent examination of the aspirate showed this and the crystals in another patient to be morphologically identical with cholesterol crystals. The findings confirm that cholesterol crystals are present in the exudate in phacolytic glaucoma and are responsible for hyperrefrigent granules. PMID- 2314849 TI - Optic nerve damage in Alzheimer's disease. AB - Optic nerves from ten patients with Alzheimer's disease were histologically examined and compared with those from age-matched controls. Specific and nonspecific measures of degeneration were noted in eight of ten Alzheimer's disease optic nerves; no degeneration was noted in any of the controls. Results of histologic examination of the retinas of one eye of three Alzheimer's disease patients also showed degeneration of retinal ganglion cells and their axons in the nerve fiber layer. Morphometric analysis suggested that in many cases of Alzheimer's disease, the optic nerve showed predominant loss of the largest class of retinal ganglion cells (M-cells) that contribute large caliber fibers to the optic nerve. The M-cell system is known to mediate specific visual functions, and selective involvement of the M-cell population leads to clinically measurable neuro-ophthalmic and psychophysical impairments in many Alzheimer's disease patients. PMID- 2314850 TI - The barrier function in extracapsular cataract surgery. AB - The distribution of fluorescein between the anterior chamber and the anterior vitreous was measured in two groups of patients after oral administration: group I, extracapsular cataract extraction (ECCE) patients with intact capsule and posterior chamber intraocular lens (PC IOL) (n = 12); group II, intracapsular cataract extraction (ICCE) patients with anterior chamber IOL (AC IOL) (n = 13). The fluorescein concentrations were measured by fluorophotometry and the penetration ratios were calculated. The penetration of fluorescein into the anterior vitreous was significantly less in the ECCE group (group I, penetration ratio = 2.03 +/- 1.00 X 10(-3) min-1; group II, penetration ratio = 5.99 +/- 4.89, X 10(-3) min-1, P less than 0.01). The authors concluded that in ECCE versus ICCE a significantly smaller proportion of fluorescein is found in the anterior vitreous relative to the aqueous after passage through the blood-aqueous barrier. This suggests a barrier to posterior movement of other molecules that may initially gain access to the eye in the anterior segment (e.g., prostaglandins). PMID- 2314851 TI - A comparison of carbon dioxide laser, liquid nitrogen cryosurgery, and scalpel wounds in healing. AB - With the carbon dioxide surgical laser, the liquid nitrogen cryoprobe, and the scalpel, wounds were created on the shaved abdomen of 24 rats, and the patterns of healing were studied. The laser wounds were the first to epithelialize, followed by the scalpel wounds, with the cryosurgery wounds the slowest to epithelialize. The results were confirmed histologically. PMID- 2314852 TI - Condylar atrophy and osteoarthrosis after bimaxillary surgery. AB - Radiographic evidence of condylar atrophy was seen in 12 patients out of 206 patients who underwent surgical orthodontic treatment. All 12 patients had the same dentofacial deformity, high-angle mandibular retrognathia (Class II open bite), and all but one had bimaxillary surgery. The etiologic factors are discussed. The dentofacial deformity is considered to be the main reason for condylar resorption, but orthognathic surgery is supposed to stimulate the progress of the disease by increased loading, disk displacement, and immobilization. PMID- 2314853 TI - The accuracy of osteosynthesis repositioning of the mandible--a stereophotogrammetric study. AB - The accuracy of repositioning of wire and plate osteosyntheses is measured by means of close-up stereophotogrammetry on cadaver mandibles. An increase of the intercondylar distance, which increases by an average of about 3.3 mm after plate osteosynthesis and by about 1.9 mm after a wire suture, is characteristic for both methods of osteosynthesis. In addition, there is a tendency to displacement of the articular condyle to caudal in osteosyntheses at the base of the mandible. PMID- 2314854 TI - Chronic facial pain associated with endodontic therapy. AB - Retrospective study was done on 118 patients who underwent nonsurgical endodontics and then surgical endodontics. Seventy-nine patients had pain before nonsurgical endodontics, and an additional 39 were pain free. After the open surgical procedure, six patients (5%) had continual pain and were considered failures. Three patients (2.5%) were thought to have had posttraumatic dysesthesia, and the other three (2.5%) were considered to have phantom tooth pain. Possible mechanisms for each chronic pain type are discussed. PMID- 2314855 TI - Cryogenically preserved adult and juvenile goat mandibular condylar transplantation. AB - Loss of a functional temporomandibular joint (TMJ) has long been a clinical challenge in both children and adults. Although reconstruction to date has been performed with various prosthetic devices or autogenous costochondral grafts, these procedures have a potential for complications and morbidity. Our studies were performed to determine the feasibility of healing, growth, and long-term function of TMJ reconstruction techniques with cryogenically preserved mandibular allografts in the goat model. This species was chosen because the surgical anatomy and biomechanics of the goat TMJ are very similar to those of the human TMJ. The positive results of the studies and their relevance will be described. PMID- 2314856 TI - Nerve entrapment in the lateral pterygoid muscle. AB - The posterior trunk of the mandibular division of the trigeminal nerve normally descends deep to the lateral pterygoid muscle. In three of 52 dissections the three main branches of the posterior trunk (lingual, inferior alveolar, and auriculotemporal nerves) were observed to pass through the medial fibers of the lower belly of the lateral pterygoid muscle. The mylohyoid and anterior deep temporal nerves also were observed to pass through the lateral pterygoid muscle in other specimens. These nerve entrapments in the infratemporal fossa provide new information concerning the anatomic and clinical relationships between the mandibular nerve and the lateral pterygoid muscle. These findings support the hypothesis that a spastic condition of the lateral pterygoid muscle may be causally related to compression of an entrapped nerve that lead to numbness, pain, or both in the respective areas of nerve distribution. PMID- 2314857 TI - The lateral medullary syndrome. AB - The lateral medullary syndrome is a rare syndrome resulting from a cerebrovascular accident involving part of the medulla oblongata with consequent loss of pain and temperature sensation in the orofacial region, loss of taste, and palatal palsy and loss of gag reflex, together with Horner's syndrome and ataxia. A case is presented and the literature reviewed. PMID- 2314858 TI - Practical applications of energy dispersive X-ray microanalysis in diagnostic oral pathology. AB - Energy dispersive X-ray microanalysis is a powerful tool that can reveal the presence and relative quantities of elements in minute particles in biologic materials. Although this technique has been used in some aspects of dental research, it has rarely been applied to diagnostic oral pathology. The purpose of this paper is to inform practicing dentists and oral specialists about the diagnostic potential of this procedure by presenting three case reports. The first case involved the identification of flakes of a metallic material claimed by a 14-year-old girl to appear periodically between her mandibular molars. In the second case, a periodontist was spared a lawsuit when a freely mobile mass in the antrum of his patient was found to be a calcium-phosphorus compound not related to the periodontal packing that had been used. The third case involved the differential diagnosis of amalgam tattoo and graphite tattoo in a pigmented lesion of the hard palate mucosa. The results of the analyses were significant and indicate a role for this technique in the assessment of selected cases. Potential for wider use of energy dispersive X-ray microanalysis in diagnostic oral pathology exists as research progresses. PMID- 2314859 TI - Which oral white lesions will become malignant? An image cytometric study. AB - We investigated the value of image cytometry in predicting the prognosis of oral epithelial lesions, whether or not they show dysplasia. Thirty-five oral epithelial lesions were studied retrospectively. Of these, 23 had later transformed to carcinoma and 12 had not. By means of the Leitz TAS image analyzer, 200 nuclei of epithelial cells and 20 nuclei of lymphocytes from each section were individually assessed for eight features related to shape and amount of stain and for six features related to chromatin pattern. The mean, standard deviation, and interquartile range of each feature were calculated, first for each section and then for each group. With the use of linear stepwise discriminant analysis we constructed a predictive model, which consisted of three variables related to chromatin pattern. The variables were mean margination, standard deviation of clumping, and standard deviation of condensation. In the jackknife classification, this model predicted the malignant potential of the lesions that later transformed to cancer with 86% predictive value and 83% sensitivity. PMID- 2314860 TI - HIV-associated periodontitis complicated by necrotizing stomatitis. AB - This report describes a case of HIV-associated periodontitis complicated by necrotizing stomatitis in a homosexual male patient with AIDS. Necrotizing stomatitis is a rapidly progressive ulcerative and necrotic infection that causes massive destruction of the oral tissues and underlying bone. Like HIV periodontitis, it appears to be related to the immune suppression caused by human immunodeficiency virus (HIV) infection; importantly, it may be life threatening. In this case, initial resolution resulted from local debridement in association with metronidazole therapy. Long-term clinical management consisted of monthly professional prophylaxis, good oral hygiene, and daily rinses with chlorhexidine. This case suggests that progressive oral necrotizing infection should be recognized as one element in the spectrum of oral manifestations of HIV infection. PMID- 2314861 TI - Factors influencing the sealing behavior of retrograde amalgam fillings. AB - In this study, the sealing behavior of apical (retrograde) amalgam fillings was evaluated with particular regard to the nature of the amalgam and the manipulative procedures used. With the use of an in vitro air pressure test, four high-copper alloys and one traditional composition low-copper alloy were selected for determination of their microleakage characteristics. Measurements were made on both normal and water-contaminated mixes, and the effect of mix plasticity was evaluated. In addition, both setting and postsetting dimensional changes of these alloys were determined. The results showed that amalgams differ in their ability to provide a complete seal and that low plasticity mixes result in greater microleakage. All zinc-containing alloys that were contaminated with water exhibited a postsetting or delayed expansion. However, only the low-copper alloy exhibited a delayed expansion of a magnitude that might induce root fracture. PMID- 2314862 TI - The use of radiographs in periapical surgery. AB - The purpose of this case report is to demonstrate the importance of radiographic examination before suturing in periapical surgery. Corrective surgery was performed to eliminate excess amalgam left in the periapical region 6 years before. The result was favorable and demonstrates the importance of radiographic examination before flap repositioning and suturing. A roentgenogram should always be made before suturing and dismissal to verify the removal of amalgam particles and to confirm that no alteration is needed. PMID- 2314863 TI - Analysis of positive cultures from endodontically treated teeth: a retrospective study. AB - A study of 12,150 endodontically treated teeth from 11,797 patients in a private patient setup revealed an incidence of 10.2% positive cultures obtained just before obturation of the root canal. Streptococcal predominance was reflected by a presence of nearly 60% in the pure culture and nearly 98% in the mixed cultures. No significant changes in microbial predominance or bacterial sensitivities were detected over the 7-year period of study. Ampicillin, cephalothin, erythromycin, and penicillin were the most effective antibiotics against the viridans streptococci, the most prevalent organism in the infected teeth. PMID- 2314864 TI - Sensitometric comparison of unexpired and expired duplicating films used in dentistry. AB - This investigation compared the sensitometric properties of unexpired and expired duplicating films. The characteristic curve derived for a duplicating film is the negative slope of a solarization curve; that is, it is different in direction to that of a regular x-ray film. An expired duplicating film is slower than an unexpired duplicating film. Unlike a negative working film, which gains fog past its expiration date, a positive working film (for example, a duplicating film) gains contrast past its expiration date. An expired duplicating film has a narrower latitude than that of an unexpired duplicating film for a useful density range. Clinically, a duplicating film can be used years after its expiration date even though there is a change in its speed and contrast. PMID- 2314865 TI - Performance of seven rapid radiographic processing solutions. AB - This study evaluated the performance of seven rapid radiographic processing products. A conventional automatic processing solution was evaluated as a standard of comparison. The products were analyzed with respect to image quality and speed. The results indicate that rapid manual processing generally involves some compromise of image quality as well as slower speeds with an accompanying increase in patient radiation exposure. Accordingly, there seems to be little motivation for the use of rapid manual processing solutions unless there is a compelling rationale in terms of time or convenience. PMID- 2314866 TI - The frequency and distribution of idiopathic osteosclerosis. AB - Full-mouth radiographs of 1921 patients were examined for the presence of radiopacities that could not be attributed to any known sources of bone formation. A total of 103 patients, or 5.4%, exhibited these foci of idiopathic osteosclerosis. Most lesions were located in the vicinity of the mandibular premolars, and the majority had some connection to the apices of the teeth. No difference in frequency between males and females was detected overall, but a statistically significant preponderance of idiopathic osteosclerosis was found in blacks, with a predilection for black females also noted. PMID- 2314867 TI - Bilateral paramolars and fourth molars. PMID- 2314868 TI - The clinical and histologic appearance of HIV-associated gingivitis. AB - Human immunodeficiency virus-associated gingivitis (HIV-G) has been described recently as a clinical entity in HIV-infected patients. However, little is known about the etiology and pathogenesis of this condition. We report a case of HIV-G in a 32-year-old man with acquired immunodeficiency syndrome (AIDS). The histology of the clinically involved gingiva revealed the absence of an inflammatory cell infiltrate. This report provides an initial description of the histologic changes occurring in HIV-G. PMID- 2314869 TI - The incidence and prevalence of hepatitis B surface antibody in a dental school population. AB - A study was undertaken to determine whether the prevalence of hepatitis B surface antibody (anti-HBs) increased among students in a dental school after exposure to patients. Predoctoral students were followed during their 4 years of dental school. An anti-HBs determination was made before patient contact and again just before graduation. Of the 247 predoctoral students initially tested, 6.1% were found to be anti-HBs positive. Of these only 145 students were tested again before graduation; four (2.8%0 who were initially anti-HBs negative seroconverted during the testing period. In addition, 31 staff, 73 graduate students and faculty, and 21 dental hygiene students were also tested for anti-HBs seroprevalence. This single test revealed 6.5% of the staff, 8.2% of the graduate students and faculty, and 4.8% of the hygienists to have the positive marker. PMID- 2314870 TI - Aarskog syndrome. A case report. AB - A rare Aarskog syndrome is reported in a 12-year-old boy. The patient had a triad of characteristic symptoms consisting of short stature, genital anomaly, and unusual facies. Both jaws were hypoplastic with presence of crowded permanent teeth and over-retained deciduous teeth. Radiographic examination of teeth showed taurodontism, which has not been reported previously. PMID- 2314871 TI - Peripheral, soft tissue odontomas. Two case reports. AB - Two cases of rare, peripheral, soft tissue odontomas, in different growth phases, are reported. Case one, discovered in an early, rapid growth phase, had no radiographic appearance, was presumed to be a periodontal abscess, and presented a diagnostic challenge. Case two was diagnosed radiographically in its mature phase. Both were treated successfully by excisional biopsy and did not recur. Comparisons are made to the classic intrabony odontomas. PMID- 2314872 TI - [The role of autotransfusion in vascular surgery]. AB - Use of autotransfusion has recently come into the limelight of clinical practice especially because of the AIDS-risk and financial considerations. Authors have analysed data of 20 patients with peripheral arterial disease at whom hemodilution were carried out before the operation with the aim of using autotransfusion. Attention is called to the importance of autotransfusion and its applicability in the practice of other sorts of surgery. PMID- 2314874 TI - [Acute kidney failure caused by rhabdomyolysis]. AB - Rhabdomyolysis developed in the muscles of the left lower extremity of a 43 year old man leading to myoglobinuria and acute renal failure. The diagnosis of rhabdomyolysis was strengthened by muscle and renal biopsy. The renal functions were restituted after peritoneal dialysis performed four times (12 hours each) within two weeks. The possible role of alcohol or Dalgol intoxication as well the disturbed circulation in the development of rhabdomyolysis is discussed. Authors point out the benefit of peritoneal dialysis in acute renal failure caused by rhabdomyolysis. PMID- 2314873 TI - [Infectious diseases and hemostasis]. AB - Authors survey the most significant haemostatic complications (thrombocytopenia, DIC, vasculitis, thrombotic microangiopathy) as well as their immune and non immune pathogenesis in infectious diseases. A short summary of therapeutic facilities and the infectious hazards of blood component therapy is also given. PMID- 2314875 TI - [Brainstem acoustic evoked potential (BEAP] in children with posterior fossa tumors]. AB - Brainstem acoustic evoked potentials (BAEPs) were recorded in 16 children with posterior fossa tumours. The results were compared with the clinical course, CT scan findings and the postmortem pathological findings. Eight children had midline medulloblastoma, four children had lateral astrocytoma (two of them cerebellar, one of them pontocerebellar, and one of them craniospinal) and four children had brainstem glioma. Different BAEP pattern could be detected according to the tumour's location and histological nature: 1. In midline medulloblastoma: bilateral, symmetrical, or slightly asymmetrical I-V. IPL prolongation was the common abnormality. Beside that, some of the patients showed III-V., or I-III. IPL prolongation, or V. depression. 2. In lateral astrocytoma: asymmetrical BAEP abnormalities were seen: unilateral V. depression, and/or I-V. IPL prolongation. 3. In brainstem glioma: severely distorted waveform could be observed, with depression and gradual disappearance of components following the wave III. Based on these results BAEP measurement seems to be useful in the differential diagnosis of posterior fossa tumours of childhood, and it can be necessary even beside the CT scan. It can be useful in the early diagnosis, because the BAEP positivity can precede the CT scan positivity, in such a case repeated CT scan required. Finally BAEP measurement proved to be effective in the follow-up of posterior fossa tumours: it can document the tumour's chemotherapeutic regression, or the progression. It is a simple, non-invasive, and cheap method. PMID- 2314876 TI - [Mononuclear cell activation in status asthmaticus]. AB - Evidence was provided by the authors, that the activity of circulating mononuclear cells is increased in status asthmaticus. An increased spontaneous secretion of chemotactic cytokin was found into the culture medium. There was no further increase in neutrophil chemotactic activity after 24 hours. In all patients a reduction was observed in the amount of neutrophil chemotactic activity after one week therapy, which is probably due to steroid treatment. No eosinophil chemotactic activity could be detected in the mononuclear cell supernatant derived from patients with acute severe asthma. The chemotactic activity was measured using a 48-well microchemotactic chamber. This mononuclear cell derived cytokin may play a role in genesis of asthmatic bronchial inflammation and provides further evidence that mononuclear cell activation is a feature of status asthmaticus. PMID- 2314877 TI - [Prothrombin and acarboxyprothrombin activity in neonates after oral and intramuscular administration of vitamin K]. AB - The effect of prophylaxis with oral or intramuscular vitamin K1 (Konakion) on the hypoprothrombinaemia and on the rate of detectable acarboxyprothrombin of full term newborns was investigated. Factor II clotting activity, factor II activity by Echis carinatus venom, factor II protein concentration and acarboxyprothrombin were determined in four groups of breast-fed infants. In the untreated group and in the group where the babies received vitamin K1 orally at birth the factor, II clotting activity was decreased and the rate of acarboxyprothrombin positive cases was increased significantly (from 30% and 28% to 55% and 52% respectively) at the 3d and 5-7th days of age. By the other two groups where 1 mg vitamin K1 was given intramusculary or 2-3 mg vitamin K1 was given orally with the first milk-feed, the factor II clotting activity increased at 3d and 5-7th days of life. In these groups the rate of acarboxyprothrombin positive babies was reduced at 3d day of life from 36% and 35% (cord blood values) to 16% and 13% respectively, and there was found acarboxyprothrombin in none of the babies at 5 7th days of life. These findings support that vitamin K1 given orally at birth is ineffective to prevent vitamin K deficiency, but when it was given with the first feed orally to well, mature babies it seems to be enable to protect the early haemorrhagic disease of the newborns. PMID- 2314878 TI - [Percutaneous balloon catheter dilatation in the therapy of mitral valve stenosis]. PMID- 2314879 TI - [Experience with the surgical treatment of superficial thrombophlebitis (varicophlebitis)]. AB - 107 patients with acute varicophlebitis of the lower limbs have been treated. In 101 cases operation were performed. These patients were treated by surgical excision of the thrombosed segments, with excision or stripping of the remaining varicosities and high saphena ligature. There were no postoperative deaths. One male patient experienced nonfatal minor pulmonary embolism. Wound-healing disturbances were observed in only 11 patients. Attention is drawn to the advantage of the surgical management. Regarding the good experiences, the authors recommend the performance of the "acute" varicectomy. PMID- 2314880 TI - [Analysis of the data from the Szabolcs-Szatmar County 1983-1987 leukemia/lymphoma registry]. AB - In Szabolcs-Szatmar county between January 1 1983 and December 31, 1987, 465 new cases of adult malignant haematologic diseases were registered by authors. The authors present the yearly distribution of cases, and analyse the main types and characteristics of the disease entity. According to their data the epidemiology of leukaemia/lymphoma in their county is equivalent to that of European and North American, therefore that may be considered as a standard for their whole country. Their work is date-collecting, it is still going on. Authors want to have more exact informations about epidemiology of leukaemia/lymphoma in their county. Their results have great importance in organizing and continuous assuring of modern treatment of haematologic malignancies. Their data would probably allow to make etiopathogenetic and therapeutic conclusions in a few years. PMID- 2314881 TI - [Hemorrhage in the abdominal cavity caused by ruptured varices]. AB - The authors report on the successful treatment of an unusual varix rupture causing intraabdominal hemorrhage in a patient who suffered from alcoholic hepatic cirrhosis. Simultaneously with the hypogastric pain, hypotension, growing circumference of the abdomen and increasing anaemia--without hematemesis or melena--referred to intraabdominal hemorrhage, which was confirmed by diagnostic paracentesis. Urgent exploratory laparotomy revealed the source of the bleeding and made the adequate surgical treatment possible. The authors are of the opinion that in case of a suspected intraabdominal hemorrhage the exploratory puncture is of diagnostic value and an operation performed without delay may ensure the improvement of the prognosis of this severe complication. PMID- 2314882 TI - [The Hungarian Chamber of Medicine addresses the readers of Orvosi Hetilap]. PMID- 2314883 TI - [Thoughts on the organization of the Hungarian Chamber of Medicine]. PMID- 2314884 TI - [Preventive value of vitamin D in various doses based on a prospective study of healthy infants]. AB - Authors have kept under review two groups of healthy full-term infants born from undisturbed pregnancy, who lived in good social conditions from birth to one year of age. One of the groups was given 500IU/die and the other 1200 IU/die vitamin D. Authors evaluated the effect of the different doses of vitamin D on the prophylaxis of the rickets. 100 infants were reviewed in both groups. The clinical, laboratory and radiological examination revealed symptoms referring to rickets at the half of infants in both groups as early as 3 month of age. In the group of infants having been given low prophylactic dose of vitamin D there was significantly larger number of patients showing clinical evidence for rickets in both ages. Also significant differences were found at the age of one year in the size of the anterior fontanelles and the head circumferences, the developing of dentition and walk and the disturbed rank of eruption of teeth. PMID- 2314885 TI - [Clinical importance of cardiac output dissociation between the right and left ventricle without evidence of an anatomical shunt]. AB - Authors took note of transitoric cardiac output dissociation between the right and left ventricle during the treatment of the acute myocardial infarction controlled hemodynamically, without the presence of a provable anatomical shunt. They demonstrate some kinds of clinical appearances and call the attention to the clinical importance of the progressive cardiac output dissociation. The re establishment of balance of the right and left cardiac output in resting position at the most optimal level of the oxygen demand, simultaneously the correction of the blood pressure and blood volume correlation can help the treatment of such acute cardiovascular cases which are complicated hemodynamic disturbances. The authors demonstrate a simple method for the registration of the cardiac output in the left and right ventricles. It has been found that the right cardiac output determined by the thermodilution method cannot be referred to the left one in such cases when the dissociation of cardiac output is present, because it can cause damage. PMID- 2314886 TI - [Ambulatory treatment of hemorrhoids using rubber band ligation and cryodestruction. Early results]. AB - Author reports about his experience with 205 patients suffering hemorrhoid disease of grade I-III. treated by rubber band ligation and cryodestruction. Follow up was carried out with the help of a questionnary. 187 answers arrived. This was the base of the investigation. 81.8 per cent of the patients gave an account of good result. The method is recommended because of its simplicity and cheapness. PMID- 2314887 TI - [Genetic and evolutionary analysis of cases of Darier's disease]. AB - In the past 10 years the authors have observed 27 people (13 men and 14 women) suffering from Darier's disease in Somogy county. Out of these 22 cases were familiar and 5 isolated. The praevalence of dysceratosis follicularis vegetans was found 1 to 16,000 in the area. In the 3 familiar cases the dysceratotic papules of Darier's disease followed the naevus-lines, drawing out the Arnosan triangle in the meantime. In the case of one of the nonfamiliar occurrences the Darier's diseased papules running stripelike also wrote out the naevus-lines, strictly localized to one side of the body. The stripes composed by the dysceratotic papules ran bipolarly in these cases too; heading from a point of the lumbosacral part of the median line of the back towards the navel. According to the authors the direction of the development of the epidermal elements of the skin is expressed in the early phase of embryonic life by the dysceratotic papules running bipolarly and following naevus-lines as embryological rudiments. PMID- 2314888 TI - [Radionuclide imaging of parathyroid adenoma using the 201TI-99mTc substraction scintigraphy method]. AB - Primary hyperparathyroidism is the most frequent parathyroid disease. Parathyroid adenomas account for the majority of primary hyperparathyroidism (81%) while carcinoma and diffuse hyperplasia occur less frequently (4% and 15%). Ten per cent of adenomas are located substernally. The difficulties of preoperative localization of parathyroid adenomas may lead to incomplete surgical removal. Therefore an accurate technique for preoperative localization of the parathyroid gland is of utmost importance. Various imaging methods are available (ultrasonography, computer tomography, angiography, etc.), each with their own limitations. Thus, a nuclear technique performed via 201Tl-99mTc dual isotope subtraction scintigraphy may well contribute to the safety of diagnostics. The authors present a case of parathyroid adenoma diagnosed by this method and confirmed histologically. The role of non-invasive techniques in preoperative localization of parathyroid adenomas protecting the patient from invasive procedures and repeated surgical explorations is highly emphasized. PMID- 2314889 TI - [Thoughts of a recently-licensed nurse on the occasion of her first day of work]. PMID- 2314890 TI - [The situation of cancer patients]. PMID- 2314892 TI - [The path to supervision]. PMID- 2314891 TI - [On Lainz, big talk and little reform]. PMID- 2314893 TI - [Supervision: help in dealing with patients]. PMID- 2314894 TI - [Working conditions of nursing personnel in Austria]. PMID- 2314895 TI - [Quality of life--quality of work]. PMID- 2314896 TI - [Methods for the reduction of psychological stress in nursing personnel]. PMID- 2314897 TI - [Positive stress control]. PMID- 2314898 TI - [Work schedule as a guarantee++ for working and living conditions]. PMID- 2314899 TI - Tax-independent binding of multiple cellular factors to Tax-response element DNA of HTLV-I. AB - The human T-cell leukemia virus type I (HTLV-I) promoter contains three copies of imperfect repeats of a 21-base pair sequence designated here as TRE (Tax-response element) that is responsive to the virally encoded transactivator protein Tax. We have identified and separated four nuclear proteins from C81-66-45 cells, an HTLV I immortalized Tax-expressing human T-lymphocyte line (Salahuddin et al., 1983), that interact with the TRE-DNA, none of which are identical with the Tax-protein. The proteins identified have molecular weights of about 32, 36 to 42, 50 and 110 kD. Four different methods were used to identify the proteins. First, from different cell lines three or all four of the nuclear proteins were specifically cross-linked by UV irradiation to the radioactively labeled TRE-DNA fragment. Second, TRE-DNA binding proteins sedimented through a glycerol density gradient at rates corresponding to proteins of native molecular weights of 35 to 50 kD and 110 kD. Third, only the 50 kD protein was retained on a biotinylated DNA streptavidin matrix when the DNA fragment contained the TRE-DNA. Fourth, extensive purification by several cycles of TRE-DNA affinity chromatography resulted in the 32, 36 to 42 and 110 kD proteins and to less extent the 50 kD factor. Two abundant proteins of 75 and 80 kD were competed out by poly[d(I-C)] in all reactions. The cAMP-response element CRE, TGACGTCA, present in the 21 base pair sequence, appears to be essential for specific protein-TRE-DNA interactions because mutation of the two G's destroys this complex. This result suggests that the cAMP response element binding protein, CREB, is involved in the protein-TRE DNA complex and in mediating the Tax response. PMID- 2314900 TI - Overexpression confers an oncogenic potential upon the eph gene. AB - The eph gene encodes a putative receptor tyrosine kinase for an as yet unknown ligand. Some human cancer cells have been found to overexpress eph mRNAs without gene amplification. We show here that NIH3T3 cells acquire tumorigenic ability in nude mice and make colonies in soft agar with a viral LTR (Long Terminal Repeat) driven artificial expression of the eph gene to a high level. This result supports the alleged contribution of overexpressed receptor tyrosine kinases to cell transformation. PMID- 2314901 TI - Lasers in otolaryngology. PMID- 2314902 TI - Lasers in tympanomastoid surgery. AB - This article describes the lasers available for use by otolaryngologists--head and neck surgeons. It emphasizes the advantages of each type for specific otolaryngologic problems and discusses the considerations for choosing the appropriate laser to treat a particular lesion. PMID- 2314903 TI - Laser surgery of tonsils, adenoids, and pharynx. AB - The author reports his experience with the laser in the treatment of lingual and palatine tonsillitis as well as with other lesions of the region. The results of laser surgery for procedures in the tonsils, adenoids, and pharynx are compared with the results of conventional surgery and electrocautery. PMID- 2314904 TI - Laser applications in ossicular surgery. AB - In the past 8 years, the author has used the laser in more than 2800 cases of tympanomastoid surgery. Of these, more than 600 involved middle ear ossicular surgery including otosclerosis, congenital deformities, and fixations of the ossicular mass for various reasons. During this time, there have been no complications, either short-term or long-term, associated with the use of the laser. There are many tasks the laser can perform with less trauma, more precision, and greater speed than conventional hand-held tools. The laser does not replace these tools in otologic surgery, but it does add an instrument that allows the microsurgeon to perform difficult tasks with greater ease and confidence. PMID- 2314905 TI - Medical staffs must maintain self-governance. PMID- 2314906 TI - Determining disability: the treating physician's role. PMID- 2314907 TI - We're all a part of the global family. PMID- 2314908 TI - A visit to the Soviet Union. PMID- 2314909 TI - The hospital and the impaired physician. PMID- 2314911 TI - Knocked-out teeth can be saved. PMID- 2314910 TI - Life after Section 89. PMID- 2314913 TI - Heart RX is patient education. PMID- 2314912 TI - HIV transmission! Potential risks for providers. PMID- 2314914 TI - No ducking the future. PMID- 2314915 TI - Doing what you can makes a difference. PMID- 2314916 TI - Effects of air pollutants and acid rain on human health. Commission on Public Health and Toxic Substances Pennsylvania Medical Society. PMID- 2314917 TI - Structure of a hospital's impaired physician committee. PMID- 2314918 TI - Know your PRO. PMID- 2314919 TI - Considering merger? Look at these issues. The Health Care Group. PMID- 2314920 TI - Preprocedure review gridlock. PMID- 2314921 TI - Tumour necrosis factor (TNF) as a mediator of macrophage helminthotoxic activity. AB - Lymphokine-activated macrophages are cytotoxic for larvae of the helminth parasite Schistosoma mansoni. That soluble secreted factors may mediate this cytotoxicity was suggested by the observation that culture supernatant fluids from stimulated macrophages also exhibited larvacidal activity. These fluids contain the monokine tumour necrosis factor (TNF). Several observations indicated that TNF is directly toxic to schistosome larvae. Cytotoxic sera taken from BCG- or S. mansoni-immunized mice after endotoxin challenge killed schistosomula in vitro, and upon gel filtration the larvacidal factor(s) in the sera co-eluted with the tumoricidal activity defined as TNF. Recombinant-derived TNF exhibited direct toxicity to schistosomula at high concentrations, or at lower concentrations in the presence of IFN gamma. The larvacidal activity of macrophage supernatant fluids was abrogated by addition of either anti-TNF antisera or Zn+2, which has been shown to inhibit TNF-induced damage of tumour cells. Anti-TNF and Zn+2 likewise suppressed schistosomulum killing by lymphokine activated peritoneal macrophages or the IC-21 macrophage line, indicating that TNF also plays a role in the effector mechanism of larval killing by whole cells. PMID- 2314922 TI - Relationships between sequestration, antigenic variation and chronic parasitism in Plasmodium chabaudi chabaudi--a rodent malaria model. AB - We describe here a rodent malaria model using cloned lines of Plasmodium chabaudi chabaudi in inbred CBA/Ca mice that exhibits both clonal antigenic variation in late stage-specific surface antigens, and deep vascular schizogony in the liver. We show that both these features are modulated by the spleen, and that surface antigen expression is crucially involved in the sequestering phenotype. Surface antigens are variant in chronic infection, and host protective immune responses can distinguish between these variants. Splenectomy abolishes this difference. The acute infection with non-sequestering cloned lines is kinetically indistinguishable from sequestering clones, but parasites unable to express variant sequestration-associated antigen do not form a chronic recrudescing infection. Another clone, able to re-express this antigen in the presence of the spleen, undergoes typical chronic recrudescence. In this model, the biological significance of sequestration-associated variant antigen seems to enable the establishment of chronic infection in the presence of a primed spleen. PMID- 2314923 TI - Larval membrane antigens protect Hereford cattle against infestation with Boophilus microplus. AB - Hereford cattle (Bos taurus) were immunized with antigens solubilized with Triton X-100 from larval membranes of the cattle tick (Boophilus microplus). Based on tick egg production compared to control cattle, vaccinated cattle were protected (78%) against challenge with 2 x 20,000 tick larvae. The soluble Triton X-100 extract of tick larval membranes was further purified by immunoaffinity chromatography, using immunoglobulin ligands (IgG1 and IgG2) from three immune steers, previously vaccinated with membrane antigens from the midgut of partly engorged adult female ticks. Cattle vaccinated with these purified antigens were protected in two separate experiments (80 and 89% respectively), against challenge with 2 x 20,000 larval ticks compared to control cattle. Whole larval membranes used as vaccines in cattle reduced the amount of eggs produced from ticks by 47% compared to control cattle, but this difference was not significant. PMID- 2314924 TI - Antigenic relatedness of stocks and clones of Trypanosoma vivax from east and west Africa. AB - The antigenic relationships of 7 stocks and 7 clones of Trypanosoma vivax from East and West Africa were compared by immune lysis. Sera from goats infected with different stocks and clones of T. vivax, collected on days 40 and 80 after infection, were used in the immune lysis test with homologous and heterologous stocks and clones of trypanosomes. Sera from infected cattle were included to compare stocks and clones from Kenya. The parasites that were used as antigen in the immune lysis tests were collected from infected mice when variable antigen type (VAT) homogeneous populations were used, from goats for infection with stocks and clones from Nigeria, The Gambia and Uganda, and from cattle for Kenyan stocks. Reciprocal cross-reactivity between sera and parasites was found between all the stocks and clones from Nigeria and The Gambia with the exception of one clone from Nigeria that was not recognized by antisera to a clone from The Gambia. There was also cross-reactivity between a stock and clone from Uganda and stocks and clones from Nigeria and The Gambia. Sera from goats infected with stocks and clones from Nigeria, The Gambia and Uganda recognized parasite populations that were homogeneous for one VAT (ILDat 1.2) of the rodent infective stock from Nigeria. Some antisera to West African stocks recognized another stable variant from a Ugandan stock adapted to rodents (ILDat 2.1), indicating that these VATs were expressed in the repertoires of the heterologous stocks. There was no cross-reaction between stocks from Nigeria, The Gambia or Uganda with Kenyan stocks. A stock from Galana (Kenya) and Bamburi (Kenya) showed reciprocal cross-reactivity. Two other Kenyan stocks, from Kilifi and Likoni, also showed cross-reactivity by immune lysis but showed no antigenic relationship with the other Kenyan stocks. PMID- 2314925 TI - Survival, strobilation and sexual maturation of Echinococcus multilocularis in the small intestine of golden hamsters. AB - Echinococcus multilocularis survived, strobilated and matured sexually in the small intestine of 6-week-old male golden hamsters that were either non-treated or treated with prednisolone tertiary-butylacetate (PTBA), following oral administration of 20 000 protoscoleces. Non-treated hamsters harboured the adult worms for up to 25 days post-infection (p.i.). Hamsters treated with PTBA from the day of infection (day 0 p.i.) harboured more adults than the non-treated, and their survival periods were extended. Moreover, a remarkable improvement in worm recovery, development and survival periods was observed in hamsters additionally treated with PTBA on days -- 14 and -- 12 p.i., and the worm development including proglottisation, sexual maturation and egg formation was comparable with that in dogs. With the present results it is suggested that Echinococcus/rodent systems represented by the E. multilocularis/golden hamsters may rejuvenate the current stagnant research on host-parasite interactions of the definitive host-stage and egg-stage of Echinococcus. PMID- 2314926 TI - A larval paralysis assay for the detection of thiabendazole resistance in trichostrongyles. AB - Infective-stage larvae of trichostrongyle nematodes, either resistant or susceptible to thiabendazole (TBZ), were incubated in eserine, an acetylcholinesterase inhibitor. Paralysis occurred in larvae treated with eserine but significant differences were observed in the percentage of larva immobilized between TBZ-resistant and TBZ-susceptible strains of the nematodes. These differences are probably related to the presence of higher levels of acetylcholinesterase in the TBZ-resistant strains than in the susceptible strains. This could be used as a rapid and inexpensive method of detecting resistance to TBZ in trichostrongyles. PMID- 2314927 TI - Blocking factors and the isolation of glutathione transferases from Hymenolepis diminuta (Cestoda: Cyclophyllidea). AB - Four acidic glutathione (GSH) transferase forms were isolated from the cytosol of the adult cestode Hymenolepis diminuta by hydroxylapatite chromatography, glutathione-affinity chromatography and chromatofocusing, pH 7-5. The enzymes were dimers of subunit size approximately 24 kDa and accounted for at least 3% of the total soluble protein. The major GSH transferase had limited catalytic activity but may interact with a range of ligands and function as a binding/passive detoxification protein. An endogenous factor interfered with the binding of the crude cytosolic GSH transferase activity to glutathione-dependent affinity matrices but, following partial purification, the GSH transferase activity successfully interacted with the glutathione affinity matrix. PMID- 2314928 TI - Transmission of taeniid tapeworm eggs via blowflies to intermediate hosts. AB - Experiments showed that dead blowflies containing eggs of Taenia hydatigena can transmit infection if ingested by lambs during grazing. Rabbits became infected with T. pisiformis after grazing grass exposed to blowflies that had been in contact with dog faeces containing the eggs of this parasite. When captive blowflies were exposed first to dog faeces containing proglottids of T. hydatigena and then to cooked meat, 100% of pigs fed on this meat became infected. The experiments are intended to model the transmission dynamics that result in human larval tapeworm infections. The implications of the results to the epidemiology of human hydatid diseases caused by Echinococcus granulosus and E. multilocularis as well as of T. solium cysticercosis are discussed. PMID- 2314929 TI - Honey bee mortality due to tracheal mite parasitism. AB - We demonstrate, by truncating the expected negative binomial distribution, that the tracheal mite parasite, Acarapis woodi, causes mortality in the European honey bee, Apis mellifera, but, that this mortality can be documented only during periods of low mite densities (mites per bee). At high mite densities, this technique no longer reveals mite-induced mortality. We suggest that this paradox results from a reduction in the mortality threshold at high mite densities, concealing mortality from our truncation procedures. Longitudinal comparisons of hive and forager bee cohorts, nevertheless, suggests mortality at all levels of infestation. We propose that persistent parasitism overcomes a colony's ability to compensate for losses, leading to its sudden decline and death. PMID- 2314930 TI - Parasite-specific antibody responses of ruminants infected with Trypanosoma vivax. AB - Sera from goats and cattle that were infected with two Trypanosoma vivax clones (ILDat 1.2 and ILDat 2.1) derived from different stocks were analysed for antibody activity against the variable surface glycoproteins (VSGs) of the infecting clones by enzyme-linked immune assays (ELISA) and immune lysis. To obtain purified VSG, lysed trypanosomes were separated on dodecyl sulphate polyacrylamide gels. The gels were copper stained and the VSG protein band was excised from the gel. After destaining, the proteins were electroeluted from the gel slices and used as antigens in ELISA. High titres of IgM and IgG1 antibodies and lytic antibodies against the VSG of the infecting clone were detected. The IgG1 response appeared about 4 days later than the IgM response. IgG2 antibodies were only detected in goats and cattle that were infected with ILDat 1.2. Two goats and two calves that were infected with ILDat 1.2 showed recurrent peaks in lytic activity and of IgM and IgG1 antibody activity to the VSG of the infecting variable antigenic type (VAT). Two goats that were infected with ILDat 2.1 showed a similar pattern, but in two other goats there was a recurrent peak only in the IgM class. Recurrent peaks of antibody activity to the VSG of ILDat 1.2 and ILDat 2.1 were not detected in the sera of goats that had been inoculated with irradiated trypanosomes or that had been infected with an unrelated T. vivax clone. The recurrence of antibody peaks against the VSG of infecting VATs suggests that trypanosomes with completely or partially identical surface determinants reappear during T. vivax infection of ruminants. PMID- 2314931 TI - [Contribution of enzyme-linked immuno-electrotransfer blot assay for the diagnosis of human neurocysticercosis]. AB - An enzyme-linked immunoelectrotransfer blot (EITB) is developed for immunodiagnosing human neurocysticercosis. The assay's efficacy is evaluated in 71 neurocysticercotic patients whose diagnosis of the disease and evaluation of disease activity is based on CT scan findings. We identified eight bands (molecular weigh less than 35 000) that evaluate the disease activity: active disease, calcification in progress, inactive disease. All samples patients with active disease recognized 14 000 band. This band is missing in the others parasitic diseases and in serum of the patients with inactive diseases or calcification in progress. The enzyme-linked immunoelectrotransfer blot is simple to perform and may be used in sero-epidemiology. PMID- 2314932 TI - [Influence of experience on the success of the treatment of chronic kidney failure by continuous ambulatory peritoneal dialysis compared with hemodialysis at a center]. AB - Experience influence on treatment success of renal chronic failure by continuous ambulatory peritoneal dialysis comparatively to hemodialysis in center is estimated by the probability variation of still being in dialysis techniques. The retrospective study was realized in 276 dialysed patients who were taken over from 1972 to April 1989. In this population, there isn't any significant difference between the probability to stay in ambulatory peritoneal dialysis or in hemodialysis in center. But, if the study is realizing from the 4 years which followed the technique introduction in the center, the success probability at 30 months, remains the same for hemodialysis in center whether the technique has began in 1972 or 1976, whereas for continuous ambulatory peritoneal dialysis, this probability raises from 52% to 72% if it begins after 1982. Ambulatory peritoneal dialysis treated patients would be maintained more longer in their system than hemodialysis patients. Those results are explaining by prevention of the peritonitis thanks to technological progress and the early prevention of possible complications. PMID- 2314933 TI - Retention of orienting reaction habituation in chronic alcoholics. AB - A polygraphic study on resistance to habituation of the somatic (EMG), autonomic (finger plethysmogram, galvanic skin reaction, respiration) and EEG (acoustic evoked potential and EEG-blocking reaction) components of the orienting reaction, elicited by a repetitive auditory stimulus during successive (weekly) sessions was performed in 67 chronic alcoholics and in 70 matched normal subjects (control group). The study showed significant retention disturbances of orienting reaction habituation (i.e., of learning), or the "saving" of stimulations, achieved from one session to the other to obtain the habituation criterion, the savings being less in alcoholics than in control subjects. The severity of habituation retention disturbances depended on patients' ages, types of alcoholism, alcohol consumption intensity and chronicity, as well as the type of resting EEG. PMID- 2314934 TI - Neuropsychological analysis of some dynamic aspects of the sexual drive in men and women. AB - In previous works the author has proposed the conception of an affect-behavioral system as the neuropsychological basis of fundamental emotions and drives. It consists of ten subsystems (SS) integrated with relations of reciprocal induction and facilitation. The SSs are: (1) SS of flight, (2) SS of aggression, (3) SS of socially channeled attack, (4) SS of mutual aid, (5) SS of autoaggression, (6) SS of food taking, (7) SS of inhibition of food taking, (8) SS of vomiting, (9) SS of sexual contacts, and (10) SS of inhibition of sexual contacts. To the activity of the different SSs correspond fundamental emotions and drives. Thus, to the activity of the SS of flight corresponds fear; to the activity of the SS of aggression, socially uncultivated anger; to the activity of the SS of sexual contacts, sexual drive; and so forth. In the paper, appropriate observations are analyzed. They reveal that the activity of the SSs of flight and vomiting can inhibit reciprocally the sexual drive; whereas, the activity of the SSs of socially channeled attack, of mutual help, and of aggression can facilitate it. The activity of the SS of autoaggression is two-sided: According to the personality structure and the situation, it can inhibit or facilitate the sexual drive. PMID- 2314935 TI - The effect of specific hypnotic suggestions on blood pressure in normotensive subjects. AB - Twenty normotensive subjects participated on a voluntary basis in an experiment designed to study the effects of specific suggestions on blood pressure (BP). After an induction procedure, the experimental group received suggestions presumed to be relatively nonactivating, although capable of lowering or raising BP. A control group was used to record the BP changes over time. All subjects met for one session. Eight subjects from the experimental group met for a second session. Both adaptation and induction resulted in significant BP decreases. A specific suggestion to increase BP gave a significant result when compared to the induction point. There was no significant change from induction to the BP decrease suggestion. Both systolic and diastolic BP behaved in the same way. A second experimental session resulted in no significant change compared with the first session. Also, no significant difference was found in suggestibility scores from the first to the second session. The results are in line with previously published studies. PMID- 2314936 TI - Influence of immobilization stress on the phospholipid composition of alveolar surfactant and lungs in rats. AB - The influence of immobilization stress on the lipid composition of alveolar surfactant and lungs in rats immobilized for 12 and 24 hours, the effects of phospholipase A2, and lipid transfer activity in alveolar surfactant were investigated. The results indicate that alveolar surfactant phospholipids underwent more significant alterations compared to lung phospholipids. Furthermore, phospholipase A2 and lipid transfer activity were reduced in alveolar surfactant of immobilized rats. The reported data suggest that the lower lipid transfer activity might be responsible for the reduced phospholipids in the surfactant system. PMID- 2314937 TI - Observation, objectivity, and the conflict of ideas. AB - The first two terms of this title are clear, representing, respectively, the guiding motto of the Society, and the common thread that unites members with very diverse interests and approaches to the understanding of behavior. Then, the last part of the title is elaborated: the conflict of ideas. This aspect is important both in terms of social values, and in terms of the interests of a scientific society operating in the modern world. Within science, there are forces that weaken genuine scientific discussion, and these need at least to be explicated so that their deleterious effects can be minimized. Finally, it is suggested that although the Society has done well in facilitating oral discussion, there is room for improvement in its readiness to engage in written intellectual conflict. PMID- 2314938 TI - Analysis of breathing patterns in a prospective population of term infants does not predict susceptibility to sudden infant death syndrome. AB - Oscillatory patterns in ventilation have been seen in term and premature infants and are indicative of the stability of the respiratory blood gas feedback control system. Apneas are related to these patterns and apnea duration is correlated with pattern characteristics. In our study breathing patterns were analyzed in recordings from 10 term infants who subsequently died of sudden infant death syndrome (SIDS) and 10 control infants matched for birth wt, gestational age, and postnatal age. Subjects were drawn from a prospectively studied population of 9856 infants. Breath-by-breath minute ventilation was estimated in each of these 24-h recordings and oscillatory patterns were detected using a comb of digital bandpass filters. Confidence limits on the filter output and a bad data flag for rejection of data during gross body movements or crying insured that only significant patterns in ventilation were evaluated. Pattern prevalence and amplitude were compared in three frequency regimes: 6- to 87-s cycle times, 6- to 28-s cycle times, and 28- to 87-s cycle times. There was no significant difference between the SIDS and the control infants in any of these pattern comparisons (paired t and Wilcoxon paired rank sum tests, p less than 0.05). In light of the normal breathing patterns found in the SIDS infants, it is unlikely that susceptibility to SIDS is distinguished, at the time of these recordings, by instability of the respiratory blood gas feedback control system. PMID- 2314939 TI - Periodic breathing and apnea in preterm infants. AB - The relationship between periodic breathing and idiopathic apnea of prematurity was investigated. We recorded respiratory impedance, heart rate, pulse oximetry and end-tidal CO2 from 68 untreated infants of less than or equal to 34 wk gestation with a diagnosis of idiopathic apnea of prematurity. Mean birth wt was 1476 g (SD 420) and mean gestational age was 29.9 wk (SD 2.6). Apneas of more than 15 s duration that were associated with hypoxemia or bradycardia were identified by semiautomated analysis of computerized records. A total of 1116 significant apneic spells were identified, only one of which occurred during an epoch of periodic breathing, five others occurred within 2 min of the end of an epoch of periodic breathing. Less than 0.6% of significant apneic spells occur within 2 min of periodic breathing. In all of the 12 infants that were monitored starting in the first 12 h of life, significant apneic spells were identified before 36 h of age and no precipitating factors were identified. Periodic breathing did not occur during the first 48 h of life, a finding that supports the concept that the peripheral chemoreceptor is inactive in the first 48 h of life. Periodic breathing in the premature infant is not a precursor to significant apnea. PMID- 2314940 TI - Morphometric study of the role of pulmonary arterial flow in fetal lung growth in sheep. AB - Pulmonary hypoplasia has been associated with absent or hypoplastic pulmonary artery in four cases in humans. Despite these reports, the effects of decreased pulmonary arterial flow on fetal lung growth have not been adequately studied. This study defines the effects of left pulmonary artery (LPA) ligation on fetal lung growth in sheep by comparing morphometrically determined pulmonary volumes from LPA-ligated, sham-operated, and un-operated control fetuses. LPA ligation (n = 5) or sham operation (n = 4) was performed at 105- to 114-d gestation. lungs were intratracheally fixed for light microscopy. At 112 d (n = 4) and at 140 d (n = 4), unoperated control fetuses were similarly delivered. Absolute pulmonary volumes were then measured using standard stereologic methods. Normal growth of the left lung from 112 to 140 d resulted in significant increases in wet and dry wt, displacement volume, and volumes of future airspace and capillary contents. LPA ligation caused significant decreases in left lung wet and dry wt, displacement volume, and in absolute volumes of fine nonparenchymal, future airspace, parenchymal tissue, and capillary contents compared to sham-operated and 140-d controls. Parenchymal tissue volume was also less than in 112-d controls. In addition, lung wt, displacement volume, and future airspace volume were significantly decreased in sham-operated fetuses compared to 140-d controls. The effects of LPA ligation on bronchial collateral circulation and factors known to affect lung growth (i.e. lung fluid volume) remain to be determined. Clearly, during the canalicular and alveolar stage of fetal lung development, pulmonary arterial flow is necessary for normal lung growth. PMID- 2314941 TI - The effect of methylprednisolone on hypoxic pulmonary vasoconstriction in the newborn late-gestation lamb. AB - Methylprednisolone (30 mg/kg), which inhibits a number of mediators of hypoxic pulmonary vasoconstriction derived from arachidonic acid, has been found to alleviate hypoxic pulmonary vasoconstriction in adult humans and in the isolated rat lung preparation. We studied the effect of 30 mg/kg of methylprednisolone on the pulmonary vascular response to hypoxia in six late-gestation newborn lambs. During hypoxia, pulmonary vascular resistance nearly doubled compared with the baseline hyperoxic state. This was true both before and after administration of methylprednisolone. We conclude that methylprednisolone, when administered at the dosage used in previous studies of adult humans and animals, does not affect the response of the pulmonary vascular bed to hypoxia in newborn lambs. PMID- 2314942 TI - The biphasic effect of amrinone on tension development in newborn mammalian myocardium. AB - The effect of the bipyridine compound, amrinone, on tension generation in neonatal and adult myocardium was studied over the concentration range 30-500 micrograms/mL. Increasing concentrations of amrinone caused a monotonic increase in twitch tension and the rate of tension development in adult papillary muscles. In contrast, lower concentrations of amrinone (30 and 100 micrograms/mL) caused a decrease in twitch tension and dP/dt in newborn papillary muscles, whereas 500 micrograms/mL amrinone caused a significant increase in both parameters in the younger age group. Lactic acid, used to dissolve amrinone, was shown to have no effect on tension development. Half relaxation time was decreased in adult preparations at all concentrations of amrinone. In comparison, the decrease in half relaxation time produced by amrinone in the newborn was significant only at a concentration of 500 micrograms/mL. Action potential duration in the newborn was significantly shortened by 30 micrograms/mL amrinone. In voltage clamp experiments, 30 micrograms/mL amrinone was shown to have no effect on tension accompanying two second voltage clamp steps to the plateau potential in newborn myocardium. Developed tension at 400 ms into the clamp step, final tension, and the ratio of early peak tension to final tension were all unchanged by the low concentration of amrinone. In contrast, 500 micrograms/mL amrinone in the newborn increased tension at 400 ms and final tension but had no effect on the ratio of early peak tension to final tension. These results suggest that the negative inotropic effect of lower concentrations of amrinone on neonatal myocardium is the result of changes in action potential configuration and not a true alteration in basic mechanisms of intracellular Ca2+ regulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314943 TI - Development of baroreflex control of heart rate in swine. AB - The purpose of this study is to describe the developmental course of arterial baroreflex control of heart rate in swine. Tests of baroreflex function were performed with eight conscious piglets serially over their first 2 mo of life. Systemic blood pressure was raised with phenylephrine (pressor test) and lowered with nitroprusside (depressor test), and stimulus-response curves relating heart rate to mean blood pressure were constructed. Baroreflex sensitivity was determined as the slope of the linear portion of the curve. Baroreflex sensitivity decreased with increasing age. Baroreflex sensitivity was not different between pressor and depressor tests except when the piglets were greater than 52 d old and sensitivity was greater with the depressor test. The heart rates at threshold and saturation, and therefore the heart rate response range, shifted to lower heart rates with increasing age. This shift was more than can be accounted for by the simultaneously decreasing resting heart rate. PMID- 2314944 TI - Effect of rotavirus infection and malnutrition on uptake of a dietary antigen in the intestine. AB - Intestinal absorption of ovalbumin (OVA), a dietary macromolecule, was studied in malnourished and normally nourished suckling mice after experimentally induced infection with rotavirus. All mice developed diarrhea within 24 to 48 h postinoculation. The malnourished animals exhibited more severe symptoms and an increased number of rotavirus-containing enterocytes in intestinal sections as compared to well-nourished mice when examined 3 d postinoculation, at the peak of diarrhea. Histopathologic examination revealed villus atrophy and pronounced vacuolization of villus enterocytes in association with malnutrition and rotavirus infection. The combination of malnutrition and viral infection resulted in more severe mucosal damage, including disruption of microvillus borders. After a single oral dose of 100 micrograms OVA at 3 d postinoculation, the concentration of OVA in serum, gastric content, intestinal lavage fluid, and intestinal tissue homogenates was measured at different time intervals. The concentrations of OVA in intestinal tissue were significantly higher in malnourished animals, whereas lower values were found in rotavirus-infected animals. In all mice, OVA was rapidly absorbed and could be consistently detected in the serum within 5 min. OVA levels peaked at 45 to 60 min and then gradually declined. In malnourished infected animals, the uptake of OVA was rapid and resulted in significantly higher serum levels when compared to well nourished or uninfected controls, respectively. The peak uptake of OVA per g body wt was about 4.5 times more in malnourished infected compared to well-nourished infected mice and 2.5 times higher in normally nourished infected animals when compared to uninfected controls. These results indicate that rotavirus infection in association with malnutrition may cause a significant rise in gut permeability to environmental macromolecules. PMID- 2314945 TI - Characterization of carbohydrate fermentation in feces of formula-fed and breast fed infants. AB - We wished to characterize the carbohydrate fermentation by intestinal flora in formula-fed infants and in breast-fed infants. We also wished to compare the carbohydrate fermentation process in the two groups to determine whether differences that existed between groups could help explain the observation that breast-fed infants usually have milder forms of acute gastroenteritis. We performed in vitro incubations of fecal samples from nine formula-fed and 14 breast-fed infants and examined the samples for fermentation characteristics, the effect of acid pH on bacterial fermentation, and changes in carbohydrate fermentation in relation to the age of the infant. Fecal samples were incubated, with and without the addition of lactose, at a pH of 6.8 and at a pH of 5.5. Volatile fatty acids and carbohydrates were determined in the incubates. The addition of lactose to the incubate at pH 6.8 resulted in significantly increased volatile fatty acid production and larger amounts of lactose, glucose, and galactose compared with the values observed in 1-h incubates to which no lactose was added. At pH 5.5, volatile fatty acid production was significantly lower in both groups compared with that at pH 6.8, and the accumulation of monosaccharides in the incubate of feces of formula-fed infants increased significantly (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314946 TI - Mineral excretion during acute, dehydrating diarrhea treated with oral rehydration therapy. AB - Twenty-four male Guatemalan children, aged 7 to 23 mo, suffering dehydration due to acute diarrhea were studied to assess their fecal endogenous losses of trace minerals zinc, iron, and copper while treated with oral rehydration therapy, either with standard or glycine-added solutions. Sodium and potassium excretions (from endogenous and exogenous sources) were also monitored. No statistically significant effect of glycine was observed on any of the minerals studied, although a tendency to higher output was seen with zinc. Median rates of fecal excretion of zinc, iron, and copper were 6.08, 6.33, and 1.61 micrograms/kg/h, respectively, whereas those for sodium and potassium were 11.2 and 9.7 mg/kg/h. All of the minerals' excretion showed significant linear correlations with fecal volume, r values were 0.47 (Zn), 0.64 (Fe), 0.77 (Cu), 0.98 (Na), and 0.97 (K). Mineral-mineral interactions also were evident, with such correlations in fecal excretion rates as: Zn versus Cu, r = 0.75; Zn versus Fe, r = 0.62; Fe versus Cu, r = 0.76. PMID- 2314947 TI - Iron retention from lactoferrin-supplemented formulas in infant rhesus monkeys. AB - Iron absorption from human milk and infant formula has received much attention, but experimental design problems have been common. In our study, iron retention from human milk, milk-based infant formula (IF) with and without supplemental ferrous sulfate, and IF supplemented with either human or bovine lactoferrin (Lf) was evaluated in infant rhesus monkeys. The exchange of 59Fe (III) Cl3 between the whey, casein, and fat fractions required up to 72 h to reach the same distribution as intrinsic iron, depending on the type of diet. Infant monkeys were intubated with labeled human milk or IF and counted in a whole body counter. Each infant received all five diets and was also intubated with a reference dose of 55Fe (II) ascorbate. There was no significant difference in iron retention (mean +/- SEM) from the experimental diets: human milk 32.5 +/- 5.1%; IF 32.1 +/- 8.0%; IF + Fe 23.0 +/- 3.9%; IF + human Lf 23.5 +/- 3.3%; IF + bovine Lf 22.7 +/- 4.9%. Therefore, infant monkeys absorb and retain iron similarly from human milk and infant formula. Supplementation of infant formula with human or bovine Lf resulted in similar iron retention to that of ferrous sulfate-supplemented infant formula. PMID- 2314948 TI - Production of generalized learning deficit and permanent growth stunting by bilateral brain stem lesions. AB - Bilateral lesions of the globus pallidus, ventrolateral thalamus, substantia nigra, or the median raphe produce a generalized learning deficit in rats. Bilateral lesions of the dorsomedial hypothalamic nuclei stunt growth in rats without significantly disturbing endocrine functions and without producing a generalized learning deficit. Globus pallidus, ventrolateral thalamus, substantia nigra, median raphe, and dorsomedial hypothalamic nuclei lesions were produced in weanling Sprague-Dawley rats to compare their effect on physical growth. At approximately 72 d of age, all lesions had resulted in reduced body wt, tail length, and tibial length. The differences lacked significance only in body wt after median raphe lesions and tail length after ventrolateral thalamus lesions. In rats with the generalized learning deficit, body size was most stunted after substantia nigra lesions. Tibial epiphyseal width was modestly increased in rats with the generalized learning deficit. Food intake/average body wt ratio in substantia nigra and dorsomedial hypothalamic nuclei rats did not differ significantly from control values. Decreases in brain, heart, liver, kidney, and testes tended to occur after all the lesions, but brain and testis organ wt/body wt ratios were either increased or unchanged. We conclude that brain lesions producing a generalized learning deficit in rats result in impaired physical growth. The results indicated that the stunted animals maintain adequate food intake and have normal growth hormone function. The anatomical substrate for generalized learning impairment may overlap with that of a set point for body size. PMID- 2314949 TI - Hypoxic injury to developing glial cells: protective effect of high glucose. AB - Hypoxic injury to differentiating glial cells is a critical event in the development of periventricular leukomalacia, the major hypoxic-ischemic lesion of the premature infant. This study has addressed the effects of hypoxia on differentiating glial cells, primarily astrocytes. Primary cultures of dissociated newborn rat brain, which are composed predominantly of differentiating astroglia, were used. Efflux of lactate dehydrogenase, an enzyme enriched in astroglia, was used to quantitate cellular injury. Three major findings are reported. First, differentiating astrocytes were resistant to hypoxic injury for many hours, although by 24 h of hypoxia severe cellular injury (lactate dehydrogenase efflux of 86% of total and morphologic changes) was obvious. Second, increase of glucose in the culture medium from the approximately physiological concentration of 5.6 to 15 mM had a marked protective effect versus hypoxia, i.e. lactate dehydrogenase efflux was totally prevented during 24 h of hypoxia in 15 mM glucose. Third, the protective effect of high glucose appeared to be related to increased utilization by glycolysis, because there was a direct correlation between the resistance to hypoxic cellular injury and the amount of lactate generated and of glucose consumed by the cells. Thus, the cells with the lowest lactate dehydrogenase efflux (and highest glucose supplementations) had medium lactate concentrations as high as 32-36 mM. These concentrations of lactate are approximately double the reported threshold concentration of lactate considered to produce cellular necrosis in in vivo models of hypoxic injury, primarily in mature animals. The data raise the possibility that hypoxic injury to differentiating glia can be prevented or ameliorated by increase in glucose availability. PMID- 2314950 TI - Energy expenditure in obese and nonobese adolescents. AB - We measured body composition, basal metabolic rate (BMR), and total energy expenditure in 28 nonobese and 35 obese adolescents aged 12-18 y using indirect calorimetry and the doubly labeled water method. BMR was highly correlated with fat-free mass in both the nonobese and obese groups (r = 0.77 and 0.84, respectively). BMR adjusted for fat-free mass was significantly greater in males than females and in the obese subjects. Total energy expenditure was significantly greater in the obese than nonobese cohort but ratios of total energy expenditure/BMR were not significantly different in the two groups (1.79 +/- 0.2 versus 1.68 +/- 0.19, nonobese and obese males and 1.69 +/- 0.28 versus 1.74 +/- 0.19 nonobese and obese females, respectively). These data indicate that BMR and total energy expenditure are not reduced in the already obese adolescent. Therefore, reduced energy expenditure cannot be responsible for the maintenance of obesity in adolescents. PMID- 2314951 TI - Simultaneous ehrlichiosis and Lyme disease. PMID- 2314952 TI - Congenital cardiac toxoplasmosis in a newborn with acquired immunodeficiency syndrome. PMID- 2314953 TI - Ventricular fluid concentrations of vancomycin in children after intravenous and intraventricular administration. PMID- 2314954 TI - Puncture wound osteochondritis of the foot caused by Pseudomonas maltophilia. PMID- 2314955 TI - Oral rehydration and breast-feeding. PMID- 2314956 TI - Childhood brucellosis: a study of 102 cases. AB - One hundred two children, 45 days to 14 years of age, with proven brucellosis were studied to illustrate the epidemiologic, clinical and laboratory findings and to assess the outcome of antimicrobial therapy. The main source of infection was the consumption of raw milk in 80% of the patients. The predominant presenting symptoms and signs were fever, arthralgia, malaise, weight loss, arthritis, hepatosplenomegaly and lymphadenopathy. Brucella melitensis was isolated from 75% of 87 patients. Diverse hematologic and biochemical abnormalities were found. Different durations and combinations of trimethoprim sulfamethoxazole or tetracycline plus streptomycin or rifampin were used for therapy. Eight-five patients were followed for an average of 14 months. Twelve (85.7%) of 14 patients treated with two-antibiotic combinations for 3 weeks relapsed, as did 5 (8%) of 62 patients treated for at least 6 weeks (P less than 0.001). No relapses occurred in 9 patients treated with trimethoprim sulfamethoxazole and rifampin for 8 to 12 weeks plus streptomycin for the first 3 weeks. Longer duration and combination of antibiotic therapy seem warranted to improve outcome and to prevent relapses. PMID- 2314957 TI - Neonatal necrotizing enterocolitis associated with delta toxin-producing methicillin-resistant Staphylococcus aureus. AB - Delta toxin-producing coagulase-negative staphylococci previously have been associated with necrotizing enterocolitis in neonates. We identified three preterm infants (body weight, 845 +/- 59 g) infected with methicillin-resistant Staphylococcus aureus (MRSA) who had a similar clinical syndrome, characterized by pustular dermatitis, bacteremia and necrotizing enterocolitis accompanied by gastric residua, abdominal distention, hematochezia and pneumatosis intestinalis. MRSA was recovered from all three infants at infected skin sites, blood or venous catheters and from two of three infants in stool specimens. Two infants also had Staphylococcus epidermidis isolated from stool. All MRSA isolates had identical microbiologic profiles: four plasmids with identical molecular weights; coproduction of enterotoxins A and B; and the same antibiotic susceptibilities. Of one skin isolate, two blood isolates and two stool isolates of MRSA that were tested, all had characteristic delta toxin hemolytic activity. All culture supernatants of these isolates evaluated for delta toxin were positive by Western blot analysis. The two strains of S. epidermidis isolated from stool were negative for delta-like toxin by a standardized enzyme-linked immunoassay. The clustering of these cases, the similarity of the clinical syndrome, and the prior association of necrotizing enterocolitis with delta-like toxins produced by S. epidermidis, suggest that delta toxin-producing MRSA (or other S. aureus isolates) also may be etiologic agents in some cases of necrotizing enterocolitis in newborns. PMID- 2314958 TI - Relationship between infant feeding and infectious illness: a prospective study of infants during the first year of life. AB - Prior studies investigating the relationship between infant feeding and infectious illnesses in developed countries have provided conflicting data about whether breast-feeding protects against common infectious illnesses early in life. These conflicts may in part be due to the failure to consider the following methodologic issues: (1) collecting data prospectively at frequent intervals for active surveillance of the detection of infections and of feeding practices, (2) specifying what is meant by infectious illnesses and breast-feeding, (3) controlling for confounding variables such as social class or presence of siblings in the household, and (4) applying appropriate analytical strategies to a population in which both feeding and exposure to illness change over time. A total of 500 infants born consecutively in a university-affiliated community hospital in Copenhagen, Denmark, were studied prospectively for the first 12 months of life by means of a detailed, monthly, mailed questionnaire that focused on feeding practices and illnesses (overall response rate, 73%). The percentage of infants who were completely or mostly breast-fed decreased from 88% at 1 month to 20% at 12 months of age. After adjustment for major covariates, no statistically significant relationship was found between the type of infant feeding and the incidence of four categories of infectious illnesses: gastroenteritis, upper respiratory illness, otitis media, and lower respiratory illness. The adjusted incidence density ratio for gastroenteritis was 1.067 (95% confidence interval = 0.982, 1.226) and for upper respiratory illnesses 0.984 (95% confidence interval = 0.883, 1.096).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314959 TI - Serum total cholesterol screening for the detection of elevated low-density lipoprotein in children and adolescents: the Bogalusa Heart Study. AB - The use of serum total cholesterol measurement was evaluated as a screening tool to predict elevated levels of low-density lipoprotein cholesterol in 2857 children and adolescents, aged 5 to 17 years, examined in 1981 and 1982. Subjects were from the biracial community of Bogalusa, Louisiana. For selected serum total cholesterol values (150 to 210 mg/dL, 3.88 to 5.43 mmol/L), sensitivities were higher for blacks than whites and higher for females than males, whereas the positive predictive values were higher for whites than blacks and higher for males than females. With the age-, race-, and sex-specific 95th percentiles of serum total cholesterol levels as cutoff points, only 44% to 50% of subjects with elevated low-density lipoprotein cholesterol levels (greater than or equal to 95th percentile) were detected, and approximately 50% of those identified had false-positive results. Lowering the serum total cholesterol cutoff point increased the sensitivity, but decreased the specificity and positive predictive value. At the 75th percentiles of serum total cholesterol levels, sensitivities were 92% to 95% for females and 100% for males and specificities were 78% to 79%, but the false-positive results increased to 81% to 84%. The low cost and ease of obtaining serum total cholesterol measurements contribute to its appeal as a screening tool for hyperlipidemia. However, its poor test characteristics make serum total cholesterol measurement inefficient as a screening tool for detecting elevated levels of low-density lipoprotein cholesterol in children and adolescents. PMID- 2314960 TI - Psychogenic seizures in children and adolescents: outcome after diagnosis by ictal video and electroencephalographic recording. AB - Psychogenic seizures in 21 nonepileptic children and adolescents, aged 8 to 18 (mean 14.5) years, were recorded by means of video recording and electroencephalography. The episodes included thrashing movements, limb jerking, or staring, with unresponsiveness. Ictal and interictal electroencephalograms showed no abnormalities after antiepileptic medication was discontinued. Fifteen patients had psychogenic seizures spontaneously during recording, and six had seizures in response to suggestion and intravenous saline injection. After the video-electroencephalographic evaluation, patients and families were told that the episodes were emotional in origin. All patients but 1 agreed to remain without antiepileptic medication, and 16 patients (76%) agreed to begin psychiatric treatment. At 6 to 66 (mean 30) months' follow-up, 14 of 18 (78%) were free of episodes. These data indicate that the majority of young patients with psychogenic seizures have a good outcome. A firm diagnosis is critical so that the episodes can be classified and emphasized as medically not worrisome, permitting a shift away from antiepileptic medication and toward psychiatric treatment. PMID- 2314961 TI - Population-based study of the developmental outcome of children exposed to chloride-deficient infant formula. AB - In 1978 and 1979 a large number of US children were fed chloride-deficient soy based infant formula. A representative sample of such children was identified in a southern county through a mailing to the homes of 3639 first- and second-grade children in the public schools. Of the 2329 (64%) who responded, 56 reported use of deficient formula and were invited to have developmental testing by one of four study psychologists at their school. Of the 310 users of other soy formulas, 112 were selected for testing as matched controls on the basis of their sex, feeding history, age, birth weight, and socioeconomic status (as indicated by school attended). After exclusions and refusals, 42 children who used deficient formula and 66 control children were tested using the McCarthy Scales of Children's Abilities. Examiners were unaware of the child's history of formula use. The mean General Cognitive Index was 102.8 in those using deficient formula and 105.4 in controls. After adjustment for demographic differences the children who used chloride-deficient formula were found to average 4.9 points less than the controls (P = .04, 1-tailed). The largest difference was in the Quantitative subscale (P = .005). These data show a statistically significant although small effect of chloride-deficient formula on the long-term developmental outcome of exposed children; however, further study of these results is needed for full confirmation. PMID- 2314962 TI - Fryns syndrome: an autosomal recessive disorder associated with craniofacial anomalies, diaphragmatic hernia, and distal digital hypoplasia. AB - Fryns syndrome is an autosomal recessive, genetically determined condition with variable expression, which includes abnormal facial features, diaphragmatic hernia, distal limb abnormalities, and malformations of the cardiovascular, gastrointestinal, genitourinary, and central nervous systems. Five cases of children with Fryns syndrome, including an example of familial recurrence and a case of long-term survival, are described. This report brings to 25 the number of cases reported in the literature and further serves to illustrate the clinical variability of this disorder. PMID- 2314963 TI - Maternal smoking and childhood asthma. AB - According to a substantial literature, passive smoking by children is associated with an increased incidence of lower respiratory illness and diminished pulmonary function. The relationship between passive smoking and childhood asthma, however, is not clear. Data from the Child Health Supplement to the 1981 National Health Interview Survey were analyzed with information about 4331 children aged 0 to 5 years to study the relationship between maternal smoking and (1) the prevalence of childhood asthma, (1) the likelihood of taking asthma medication, (3) the age of onset of children's asthma, and (4) the number of hospitalizations among children with and without asthma. An odds ratio for asthma of 2.1 was shown by multivariate logistic regressions among children whose mothers smoke 0.5 packs of cigarettes or more per day compared with children of nonsmokers (P = .001). In similar analyses maternal smoking of 0.5 packs per day was identified as an independent risk for children's use of asthma medications (odds ratio 4.6, P = .0006) and for asthma developing in the first year of life (odds ratio 2.6, P = .0006). Maternal smoking is also associated with increased numbers of hospitalizations by its association with an increased risk of asthma as well as by contributing to hospitalizations independently of a child having asthma. Among children with asthma, however, maternal smoking is not associated with increased numbers of hospitalizations. It was concluded that maternal smoking is associated with higher rates of asthma, an increased likelihood of using asthma medications, and an earlier onset of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314964 TI - Screening for biotinidase deficiency in newborns: worldwide experience. AB - Between January 24, 1984, and December 31, 1988, 29 screening programs for biotinidase deficiency in newborns were established in 12 countries, and 4,396,834 newborns were screened. The worldwide incidence is based on screening programs in Australia, Austria, Canada, Italy, Japan, Mexico, New Zealand, Scotland, Spain, Switzerland, The United States, and West Germany. Biotinidase deficiency was detected in 72 newborns; 32 had profound biotinidase deficiency (less than 10% of mean normal activity level) and 40 had partial deficiency (10% to 30% of mean normal activity level). The combined incidence of profound and partial deficiency was 1 case per 61,067 live births (1:49 500 to 1:79 544; 95% confidence interval), the estimated frequency of the recessive allele was 0.0040, and the frequency of heterozygosity was estimated to be 1:123. Profound deficiency occurred in 1 per 137,401 live births (1:109,300 to 1:211,200), and partial deficiency in 1 per 109,921 live births (1:86,600 to 1:159,700). Most available parents of children with profound and partial deficiency had biotinidase activity levels intermediate between zero and mean normal activity levels. Six children with profound deficiency were symptomatic at, or soon after, the time of diagnosis; no infant with partial deficiency has become symptomatic, but little is known about the natural history of infants with partial deficiency. Most children whose biotinidase deficiency was detected by newborn screening were white, one was black, and one Hispanic; biotinidase deficiency has not been detected in Oriental children. Although 8 pilot programs have terminated, 21 will continue either indefinitely or until predetermined targets are reached, and 3 new programs were scheduled to begin in January 1989.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2314965 TI - Di George anomaly and velocardiofacial syndrome. AB - The velocardiofacial syndrome is an autosomal dominant disorder characterized by cleft palate, cardiac anomalies, characteristic facies, and learning disabilities. The Di George anomaly involves developmental defects of the third and fourth pharyngeal pouches, resulting in thymic and parathyroid hypoplasia and cardiac defects. The cases of individuals in two families help substantiate the notion that the Di George anomaly occurs as a feature of the velocardiofacial syndrome. The proband in family 1 was a male infant with persistent hypocalcemia and cardiac defects consisting of truncus arteriosus, atrial septal defect, ventricular septal defect, and abnormal aortic arch vessels. Autopsy revealed absence of thymic and parathyroid tissue, and the Di George anomaly was diagnosed. His father had a submucous cleft palate, T cell dysfunction, and facial features consistent with the velocardiofacial syndrome. This is the third case of male-to-male transmission of velocardiofacial syndrome. The proband of family 2 was a 4-year-old girl with developmental delay, persistent neonatal hypocalcemia, ventricular septal defect, T cell dysfunction, and facial features of the velocardiofacial syndrome. The Di George anomaly has been reported to occur in at least 18 different disorders. The observation that the Di George anomaly is a component manifestation of the velocardiofacial syndrome in these two families provides further evidence that the Di George anomaly is not a distinct syndrome of a single origin but rather a heterogeneous developmental field defect. It is proposed that all previously reported cases of autosomal dominant Di George anomaly are examples of the velocardiofacial syndrome. PMID- 2314966 TI - Percutaneous catheterization of the axillary vein in infants and children. AB - The axillary vein was evaluated as an alternative access site for central venous catheterization in critically ill infants and children. Children were placed in the Trendelenberg position (when possible) with arm abducted 100 to 130 degrees. The vein was entered parallel and inferior to the artery. Success rate for catheterization was 79% (41/52). Catheter diameter range was 3 to 8.5 F and catheter length range was 5 to 30.5 cm. Median patient weight was 7.0 kg (3.0 to 59 kg). Median age was 0.91 years (14 days to 9 years). All central lines ended in the subclavian, innominate, or superior vena cava. Median catheter duration was 8 days (2 to 22 days). A total of 338 patient catheter-days were studied. Central venous pressure was successfully monitored in five of five attempts. Complications with insertion (3.8% of attempts) included one pneumothorax and one hematoma. Complications during catheter duration (9.8% of catheters, 1.1% per catheter-day) included one instance each of venous stasis, venous thrombosis, catheter sepsis, and parenteral nutrition infiltration. No complication contributed to a patient mortality. Success and complication rates were comparable with those in jugular catheterization studies in children. The axillary approach is an acceptable route for central venous catheterization in critically ill infants and children. PMID- 2314967 TI - Tentorial hemorrhage associated with vacuum extraction. AB - The clinical and radiologic descriptions of three neonates with tentorial hemorrhage after vacuum extraction are reported. All patients were full term, with Apgar scores of 8 or more; one patient experienced fetal distress during delivery. Within 36 hours after birth, the neonates had multiple generalized seizures; computed tomography or magnetic resonance imaging outlined distinctive tentorial hemorrhages with extension over the superior surface of the cerebellum or inferior surface of the occipital lobe. One patient had diffuse hypoxic ischemic injury, and another had bilateral temporal lobe infarcts. Treatment included medical control of seizures and intracranial hypertension; one patient had surgical evacuation of bilateral subdural hematomas. Follow-up from 1 to 5 years showed significant developmental delays in two patients. These cases demonstrate that the forces generated on the fetal cranium by vacuum extraction are similar to those produced by forceps and result in tentorial laceration, venous rupture, and subdural hemorrhage. Because these hemorrhages may be associated with significant ischemic injury, serial radiologic evaluation is recommended for the detection of persistent structural abnormalities. PMID- 2314968 TI - Establishing special needs car seat loan program. AB - Car seat loan and rental programs have provided many families with low-cost access to child restraints. When an infant or child is unable to be accommodated in a standard car seat or seat belt owing to physical or medical problems, parents of these children have few, if any available resources. The establishment and operation of a loan program at the Indiana University School of Medicine for children who are medically fragile is reviewed in this article. This program was developed by the Automotive Safety for Children Program at the James Whitcomb Riley Hospital for Children, Indiana University Medical Center, to meet the special transportation needs of children with respiratory, orthopaedic, and other medical and physical difficulties. A summary table is included to highlight restraints that have performed satisfactorily during dynamic crash tests and are used to meet patient transportation needs at Riley Hospital. Guidelines for establishing and maintaining a child restraint loan program for children with special needs are outlined to encourage replication of this effort. PMID- 2314969 TI - Assessment of temperament in the toddler age group. AB - We used the Toddler Temperament Scale with large representative samples of younger (mean age = 20.5 months; N = 1188) and older (mean age = 35.4 months; N = 1360) Australian toddlers. There were significant sex differences on 6 of the temperament dimensions for the young group, and on 5 of the 9 dimensions for the older group. Older boys were also more likely to be categorized clinically as having a "difficult" temperament and less likely to have an "easy" temperament. Each group was divided into quartiles according to socioeconomic status. For the younger toddlers there were significant differences in 3 of 9 temperament dimensions, and for the older group there were significant differences in 7 of 9 dimensions. Groups with higher socioeconomic status had temperament ratings which were more likely to make them easier to manage, and to be categorized clinically as having an easy temperament, but toddlers with low socioeconomic status were more likely to have a difficult temperament. There were significant differences in temperament dimension scores between Australian toddlers and those studied in an American setting. These results indicate that toddler temperament ratings differ according to age, sex, social class, and cultural context. Great caution needs to be taken in interpreting individual temperament profiles utilizing comparison data obtained from different sociocultural settings. Future temperament "norms" may need to specify characteristics of the group of children from which they were derived to allow more valid comparisons. PMID- 2314970 TI - Retinal hemorrhage after cardiopulmonary resuscitation in children: an etiologic reevaluation. PMID- 2314971 TI - Transient organic aciduria and methemoglobinemia with acute gastroenteritis. PMID- 2314972 TI - A horrifying television commercial that led to constipation. PMID- 2314973 TI - Gas embolism after ingestion of hydrogen peroxide. PMID- 2314974 TI - Repeated oral administration of activated charcoal for treating aspirin overdose in young children. AB - The data from our two patients indicates that gastrointestinal dialysis with repeated oral doses of activated charcoal may significantly enhance the elimination of overdoses of salicylate in young children. Limited experience precludes precise recommendations, but current evidence suggests that gastrointestinal dialysis should be evaluated further for treating pediatric salicylate intoxication. PMID- 2314975 TI - An unlucky rabbit's foot? PMID- 2314976 TI - Hereditary fructose intolerance in the vomiting infant. PMID- 2314977 TI - American Academy of Pediatrics Committee on Hospital Care: Medical staff appointment and delineation of pediatric privileges in hospitals. PMID- 2314978 TI - American Academy of Pediatrics Committee on Fetus and Newborn: Recommendations on extracorporeal membrane oxygenation. PMID- 2314979 TI - Fluctuating blood pressure and intraventricular hemorrhage. PMID- 2314980 TI - Ceftriaxone vs cefotaxime for treatment of Haemophilus influenzae meningitis. PMID- 2314981 TI - Topical skin anesthesia before inserting hemodialysis cannula. PMID- 2314982 TI - Rickets and metabolic disorders. PMID- 2314983 TI - Intensive care management of acute asthma in children. PMID- 2314984 TI - Parental presence in the emergency department. PMID- 2314985 TI - Solar intensity and sun protection. PMID- 2314986 TI - Dangers of arterial catheters in critically ill neonates. PMID- 2314987 TI - Evaluating persistent sleeplessness in children. PMID- 2314988 TI - Maternal cocaine use during pregnancy: effect on the newborn infant. PMID- 2314989 TI - Current status of Haemophilus influenza type b vaccines. PMID- 2314990 TI - Conditions for the transition to home health care. AB - A number of changes in health care thinking have been taking place during the past years; these changes are in the financial system, in professional thinking and in political views. As one of the consequences, general hospitals in the Netherlands are thinking of entering home health care for professional and financial reasons. Most probably this may be done now if the management dares to take some risks. However, many conditions still need to be adapted to that situation. Most importantly, it is absolutely necessary to achieve a functional co-operation between professional groups in home health care. Hospital pharmacists should do their home work to make clear what extra value they can bring into home health care. Undoubtedly there are possibilities for the hospital pharmacy in home health care as part of the whole hospital policy in that direction. PMID- 2314991 TI - Possibilities of continuous care. Part I. AB - The continuity of health care in the Netherlands is hampered by its structure. There exists a sharp border between the first echelon in which the primary general care is given and the higher echelons in which the out-patient and hospital care is delivered. The policy of the Government is directed to substitution of out-patient and hospital functions, executed in primary care. The possibilities and difficulties for patients and pharmacists are discussed. PMID- 2314992 TI - Possibilities of continuous care. Part II. AB - In this article the growing need and necessity to accomplish a shift from in patient care towards out-patient care, and the role of the hospital pharmacists after this shift has been accomplished, are discussed. If certain obstacles, which still hamper the development towards home care are overcome, then--given the hospital pharmacist's possibilities and limitations--his task in patient care, although important, seems limited. Besides, several other provisions have to be made before the hospital pharmacist comes into the picture. On the other hand, other contributions to health care in general, such as contributions to journals, helping with executing research, information to the public and participation in pharmaceutical consultation groups, have increased and are also important. Although these contributions may already have been realized, they could be more firmly structured, extended and intensified. PMID- 2314993 TI - Intramural and extramural health care in the United Kingdom. AB - In this article the factors which determine whether health care in the United Kingdom is provided in hospital, at home or through intermediate or shared care arrangements are considered. The following aspects of home health care in the United Kingdom are discussed: continuous ambulatory peritoneal dialysis; parenteral nutrition; cytotoxic therapy; terminal care/pain control; intravenous antibiotics. Pharmaceutical implications of the transfer of the long-term care of the mentally ill, mentally handicapped and elderly from hospital to community settings are also considered. Key changes in the development of pharmacy in the United Kingdom are mentioned and the emergence of a new group, community service pharmacists, is identified. PMID- 2314994 TI - Home health care in France. AB - Home health care in France has a long tradition, but is limited in its development. Since 1970 hospitals are by law permitted to extend services at home. Apart from this, patient associations are a driving force in the organization of home health care. There is a trend to more home health care, but this is hampered by splitting of responsibilities of local, departmental or central authorities. The hospital pharmacist is recommended to focus on his scientific and technical competence. Improved relations between community pharmacists and hospital pharmacists are advocated. PMID- 2314995 TI - The challenge of health care developments for hospital pharmacy. AB - The traditional role of hospital pharmacists in drug analysis and drug compounding broadened to a patient-oriented approach during the sixties and seventies. The clinical pharmacy concept was adopted. This practice includes daily-prepared total parenteral nutrition and chemotherapy, sophisticated analgesic systems, individualized drug distribution and specific information. The hospital pharmacy provides aseptic procedures as well as specialized logistics. Clinical pharmacy practice concentrates on tailor-made pharmaceutical care. As home health care usually deals with therapeutic modalities, this approach offers great possibilities for highly skilled out-patient care. Financial and legal interferences and the traditional gap between in-patient care and out-patient care must be removed. Home health care challenges the hospital pharmacists to place his knowledge and abilities at the disposal of this new type of patient care. PMID- 2314996 TI - Technology and health care. AB - The invasion of technology, both in society and health care, asks for critical assessment of efficacy and safety. In a greying population hospital care will be substituted by home care in the treatment of chronic diseases. Continuity of care, between hospital and home, requires good communication between physician, patient and family. The hospital pharmacy has an essential role in providing treatment material in renal dialysis, chemotherapy or parenteral nutrition, the instruction of patients and the quality control of diagnostic tests and new devices for drug administration. The surveillance of complex medication, especially in the elderly, is an important part of that consultancy. The hospital pharmacist, in order to take up his place in the treatment team, should become familiar with new and technical aspects of drug administration in home care setting and the safety of its transfer from hospital to home. PMID- 2314997 TI - Practical aspects of extramural pharmaceutical care. PMID- 2314998 TI - Integration of pharmacotherapy. PMID- 2314999 TI - Choice of drugs: always a compromise. PMID- 2315000 TI - Gene technology and the drugs of tomorrow. AB - The progress of pharmaceutical research depends on three factors: on the evolution of medical needs, on societal attitudes, and on scientific and technical feasibility. Among the factors which are 'internal' to science, molecular biology seems to be the most important driving force, at least for the foreseeable future. The influence of molecular biology on pharmaceutical research is occurring in several distinct phases. The first phase was characterized by the use of gene technology as a production instrument for known proteins. In the second phase, gene technology is instrumental in the identification of novel proteins and in the elucidation of their gene structure and physiological function. A great number of proteins which have therapeutic potential will eventually emerge from this phase, with the more important ones like the hematopoietic factors yet to come. During the third phase, gene technology will provide proteins that can serve as pharmacological tools: receptors, ligands, enzymes, cytokines and other proteins provided by gene technology will enable us to open up new fields of pharmacology from which novel drugs, often low molecular weight chemical entities, will emerge. Finally the fourth phase will be characterized by a knowledge of gene structure and regulation extensive enough to develop a pharmacology of gene regulation and to establish somatic gene therapy. New drugs that can be expected to emerge from the interaction of molecular biology and pharmaceutical research within the next ten to twelve years are discussed. It is expected that pharmaceutical research will in the end be transformed into a discipline in which molecular biology and structural chemistry play dominating roles while synthetic chemistry will be reduced to the role of an important tool. PMID- 2315001 TI - Pinacidil activates the ATP-sensitive K+ channel in inside-out and cell-attached patch membranes of guinea-pig ventricular myocytes. AB - Patch-clamp techniques were used to study the effects of pinacidil on the adenosine-5'-triphosphate (ATP)-sensitive K+ channel current in guinea-pig ventricular myocytes. In inside-out patches, the ATP-sensitive K+ channel current could be recorded at an internal ATP concentration of 0.5 mM or less and almost complete inhibition was achieved by raising the concentration to 2 mM. Application of pinacidil (10-30 microM) in the presence of 2 mM ATP restored the current, whereas 5 mM ATP antagonized the effect of pinacidil. The conductance of the channel at symmetrical K+ concentrations of 140 mM was 75 pS with a slight inward rectification at voltages positive to + 40 mV. There was no significant change in the conductance after application of pinacidil. In 0.5 mM ATP, at -80 mV, both the distributions of the open time and the life-time of bursts could be fitted by a single exponential. An increase in ATP concentration decreased the mean life-time of bursts, whereas pinacidil increased it with little increase in the mean open time. Closed time distributions of the channel were fitted by at least two exponentials, with a fast and a slow time constant. An increase in ATP concentration markedly increased the slow time constant associated with a decrease in the number of bursts, whereas the effect of pinacidil was opposite to that of increased ATP. These results indicate that pinacidil increases the open state probability of the ATP-sensitive K+ channel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2315002 TI - Dimethyl sulfoxide elevates intracellular Ca2+ and mimics effects of increased light intensity in a photoreceptor. AB - A 1% (v/v) solution of dimethyl sulfoxide (DMSO) added to the saline bath of isolated Balanus eburneus photoreceptors increased receptor potential amplitude by 40-50% and shortened time to peak amplitude and latency by 20-25%. The light sensitive membrane current of voltage-clamped cells was increased systematically as DMSO concentration was increased from 1% to 10%. The null potential of the light sensitive current was unaffected by DMSO with short pulses of light, indicating that DMSO has no direct effect on ion selectivity of the light sensitive channel. Absorbance changes of cell injected with the calcium indicator arsenazo III show that DMSO elevates intracellular Ca2+ (Cai). Current-voltage relations in darkness reveal that DMSO induces a small sustained inward current (approximately 5 nA) which has a null potential similar to the light-induced current. DMSO may activate the light-sensitive conductance via the increase in Cai. However, the altered kinetics and increased amplitude of the receptor current are opposite to the desensitizing effects normally observed with increased Cai. PMID- 2315003 TI - The effect of high-intensity exercise on the respiratory capacity of skeletal muscle. AB - The effect of high-intensity exercise on the respiratory capacity of skeletal muscle was studied in horses which ran five 600-m bouts on a track with 2 min of rest between exercise bouts, or once to fatigue on a treadmill at an intensity that elicited the maximal oxygen uptake. Venous blood and biopsy samples of the middle gluteal muscle were collected at rest, after each exercise bout, and 30 and 60 min post-exercise. Blood samples were analyzed for lactate concentration and pH and muscle samples for metabolites, pH, and respiratory capacity. Venous blood and muscle pH declined to 6.91 +/- 0.02 and 6.57 +/- 0.02, respectively, after the fifth track run and to 6.98 +/- 0.02 and 6.71 +/- 0.07, respectively, after treadmill running. Muscle metabolite changes were consistent with the metabolic response to high-intensity exercise. Muscle respiratory capacity declined greater than 20% (P less than 0.05) after a single exercise bout and was 45% of the control value after the fifth track run. Tissue respiration was depressed 60 min post-exercise but was normal 24 h later. These observations suggest that high-intensity exercise impairs the respiratory capacity of the working muscle. Although this occurred in parallel with reductions in pH, other factors could be responsible for this response. PMID- 2315004 TI - A rapidly inactivating Ca2(+)-dependent K+ current in pheochromocytoma cells (PC12) of the rat. AB - The membrane electrical properties of undifferentiated pheochromocytoma cells of the rat (PC12) were studied using both current- and voltage-clamp techniques with the use of low-resistance blunt-tipped micropipettes (patch electrodes). In the presence of tetrodotoxin (TTX, 2-3 microM), a spike-like wave form with a prominent after-hyperpolarization (AHP) was recorded following brief (less than 10 ms) depolarizing current pulses. The inorganic divalent cations, Cd2+ (0.5 mM), Mn2+ (4 mM), and 0 mM Ca2+/4 mM Mg2+ solution prolonged the duration, attenuated the AHP, slowed the rate of repolarization, and slightly enhanced the amplitude of this wave form. A rapidly inactivating outward current was recorded in over 70% of the cells under voltage-clamp conditions. This transient current was elicited at about -30 mV, and was blocked by tetraethylammonium (5 mM), inorganic divalent cations (Cd2+, 0.5 mM; Mn2+, 4 mM; Ba2+, 3 mM), and removal of Ca2+ (0 mM Ca2+/4 mM Mg2+) from the local perfusion medium. In addition, 4 aminopyridine (5 mM), which blocks the transient outward K+ current IA in a variety of excitable cells, did not have any appreciable effect on this rapidly inactivating current. Moreover, it was possible to elicit the current at a holding potential of -40 mV. The reversal potential of this current was -90 mV, and shifted positively when extracellular K+ concentrations were elevated. It is concluded that PC12 cells have a rapidly inactivating Ca2(+)-dependent K+ current. A possible explanation for the transient nature of this current may be the presence of an effective intracellular Ca2+ buffering (uptake or extrusion) system. PMID- 2315005 TI - The luminal K+ channel of the thick ascending limb of Henle's loop. AB - In vitro perfused rat thick ascending limbs of Henle's loop (TAL) were used (n = 260) to analyse the conductance properties of the luminal membrane applying the patch-clamp technique. Medullary (mTAL) and cortical (cTAL) tubule segments were dissected and perfused in vitro. The free end of the tubule was held and immobilized at one edge by a holding pipette kept under continuous suction. A micropositioner was used to insert a patch pipette into the lumen, and a gigaohm seal with the luminal membrane was achieved in 455 instances out of considerably more trials. In approximately 20% of all gigaohm seals recordings of single ionic channels were obtained. We have identified only one single type of K+ channel in these cell-attached and cell-excised recordings. In the cell-attached configuration with KCl or NaCl in the pipette, the channel had a conductance of 60 +/- 6 pS (n = 24) and 31 +/- 7 pS (n = 4) respectively. In cell-free patches with KCl either in the patch pipette or in the bath and with a Ringer-type solution (NaCl) on the opposite side the conductance was 72 +/- 4 pS (n = 37) at a clamp voltage of 0 mV. The permeability was 0.33 +/- 0.02 . 10(-12) cm3/s. The selectivity sequence of this channel was: K+ = Rb+ = NH4+ = Cs+ greater than Li+ much greater than Na+ = 0; the conductance sequence was K+ much greater than Li+ much greater than Rb+ = Cs+ = NH4+ = Na+ = 0. In excised patches Rb+, Cs+ and NH4+ when present in the bath at 145 mmol/l all inhibited K+ currents out of the pipette. The channel kinetics were described by one open (9.5 +/- 1.5 ms, n = 18) and by two closed (1.4 +/- 0.1 and 14 +/- 2 ms) time constants. The open probability of this channel was increased by depolarization. The channel open probability was reduced voltage dependently by Ba2+ (half maximal inhibition at 0 mV: 0.07 mmol/l) from the cytosolic side. Verapamil, diltiazem, quinine and quinidine inhibited at approximately 1 mumol/l -0.1 mmol/l from either side. Similarly, the amino cations lidocaine, tetraethylammonium and choline inhibited at 10-100 mmol/l. The channel was downregulated in its open probability by cytosolic Ca2+ activities greater than 10(-7) mol/l and by adenosine triphosphate greater than or equal to 10(-4) mol/l. The open probability was downregulated by decreasing cytosolic pH (2-fold by a decrease in pH by less than or equal to 0.2 units).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2315006 TI - Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels. AB - Intracellular recordings were made from neurones located in the ventromedial hypothalamic nucleus (VMHN) of slices from rat hypothalamus. These neurones were hyperpolarized on removal of extracellular glucose, resulting in an inhibition of firing, actions which were reversed on the re-introduction of glucose. No reversal of the inhibition of firing was observed when 10 mM mannoheptulose, an inhibitor of glucose metabolism, was present in addition to glucose. Increasing the mannoheptulose concentration to 20 mM resulted in further hyperpolarization. Cell-attached recordings from isolated neurones revealed that an increase in extracellular glucose inhibited a K+ channel and increased action current activity. ATP induced closure of this K+ channel when applied to inside-out membrane patches. Closure was also induced by Mg-free ATP or the non-hydrolysable ATP-analogue, adenylylimidodiphosphate indicating no requirement for ATP metabolism. We suggest that the closure of ATP-sensitive potassium channels underlies increased hypothalamic firing following an increase in extracellular glucose. PMID- 2315007 TI - Stimulus-specific patterns of myosin light chain phosphorylation in smooth muscle of rabbit thoracic artery. AB - When the rabbit thoracic artery was stimulated with submaximal concentrations of agonist [40 mM K+, 30 microM prostaglandin F2 alpha (PGF2 alpha) or 7 microM histamine], about 90% of a maximal contraction occurred. Each agonist induced a rapid development of contraction followed by a sustained response. The maximal rate of force generation stimulated with PGF2 alpha was twice that seen with K+ or histamine. Stimulation with 40 mM K+ increased the extent of monophosphorylated 20 kDa myosin light chain (MLC-P) for up to 1 min to a maximal value of 38.8 +/- 1.0%, there was a subsequent rapid decrease and the MLC-P level remained just above the basal value for 40 min (6.8 +/- 3.0%). In the case of stimulation with 7 microM histamine, MLC-P level increased rapidly and was sustained for up to 40 min (28.0 +/- 4.9%). In contrast to the stimulation with K+ or histamine, PGF2 alpha induced both mono- and diphosphorylated MLC20 (MLC-P and MLC-P2 respectively) at a low concentration (3 microM). The monophosphorylation of MLC20 induced by 30 microM PGF2 alpha reached the maximal value of 32.8 +/- 5.2%, and was sustained for up to 40 min (15.2 +/- 5.4%). The diphosphorylation of MLC20 increased rapidly (7.4 +/- 4.0% at 5 min), then decreased to the basal value within 40 min. These results suggest that different modes of stimulation of smooth muscle contraction produce different profiles of MLC20 phosphorylation. The implications of these observations are that the diphosphorylated form, specifically induced by certain agents, may modify the mode of contraction of the aortic artery. PMID- 2315008 TI - Calibration of photodiode measurements of cell motion by a transmission optical lever method. AB - A method of calibrating photodiode measurements of cell motion is described. A transparent glass plane is inserted perpendicular to the light path, in front of the photodiode. When the glass plane is rotated, changing the angle between the plane and the light path, the image is displaced. The rotatable glass plane acts as an optical lever to simulate cell motion. The optical lever is easy to construct and offers excellent linearity and accuracy. PMID- 2315009 TI - Ophidian kidney preparation for the measurement of glomerular dynamics in real time. AB - A new ophidian kidney preparation is described which allows the measurement of glomerular arteriolar diameters, glomerular blood flow, and glomerular capillary pressure in real time. Intravital epifluorescence video microscopy is utilized to observe and record blood flow in the renal microcirculation in the garter snake, Thamnophis sirtalis. Carotid, renal artery and glomerular capillary pressures are recorded digitally on the video recording simultaneously with the images with an eight-channel video data recorder, maintaining synchrony of all data. On the video replay, glomerular arteriolar diameters are measured with a video micrometer and RBC velocity determined with the video dual-slit method. Blood flow is continuously calculated from the diameter and RBC velocity measurements. The continuous and simultaneous measurements of the pressure gradient across the afferent limb of the glomerular circulation, the renal artery to glomerular capillary pressure drop, and the rate of glomerular blood flow allow the continuous calculation of afferent glomerular arteriolar resistance in real time. This is the first demonstration of these capabilities in a vertebrate kidney. PMID- 2315010 TI - Modulation of ATP-sensitive potassium channel activity by flash-photolysis of 'caged-ATP' in rat heart cells. AB - We have used 'caged-ATP' to investigate the kinetic behavior of KATP channels in ventricular cells from rat heart. In whole cells, loaded with 'caged-ATP', an increase of intracellular [ATP] following a UV light flash produced a decrease of KATP channel current that was too slow (tau approximately 300 ms) to be explained by the expected time-course of ATP release (tau approximately 3 ms) and the time course of channel blockade by ATP (tau approximately 20 ms). In isolated membrane patches, caged-ATP itself caused partial blockade of KATP) channels. Under these conditions, photorelease of ATP caused channel activity to decline further. The results suggest that caged-ATP can bind to the KATP) channel but, on binding, decreases the open probability to a lesser extent than does ATP. Additionally, the observations indicate that for photolytically-generated ATP to bind to the channel, caged-ATP must first unbind (slowly) from the channel. We conclude that 'caged-ATP' is not fully caged with respect to its allosteric action on the KATP channel. PMID- 2315011 TI - Is potassium co-transported by the cardiac Na-Ca exchange? AB - It has been suggested that the stoichiometry of the electrogenic Na-Ca exchange is 3Na:1Ca. Recently, however, it was reported in rod outer segments that the stoichiometry of Na-Ca exchange is not 3Na:1Ca but 4Na:1Ca + 1K. In cardiac cells, the reversal potential has always been measured in the absence of K or at a very low K concentration. We have, therefore, re-examined the reversal potential of the Na-Ca exchange current by whole-cell voltage clamp in single guinea-pig ventricular cells in the presence of K on both sides of the membrane. The Na-Ca exchange current reversed at potentials close to the calculated values for 3Na:1Ca stoichiometry even in the presence of K. The magnitude of the Na-Ca exchange current did not change in 1 and 10 mM [K]o. We therefore conclude that K is not co-transported by cardiac Na-Ca exchange and its stoichiometry is 3Na:1Ca. PMID- 2315012 TI - Single Ca2(+)-activated K+ channels in excised membrane patches of hamster oocytes. AB - The properties of the Ca2(+)-activated K+ channel in unfertilized hamster oocytes were investigated at the single-channel level using inside-out excised membrane patches. The results indicate a new type of Ca2(+)-activated K+ channel which has the following characteristics: (1) single-channel conductance of 40-85 pS for outward currents in symmetrical K+ (150 mM) solutions. (2) inward currents of smaller conductance (10-50 pS) than outward currents, i.e. the channel is outwardly rectified in symmetrical K+ solutions, (3) channel activity dependent on the internal concentration of free Ca2+ and the membrane potential, (4) modification of the channel activity by internal adenosine 5' diphosphate (0.1 mM) producing a high open probability regardless of membrane potential. PMID- 2315013 TI - NLN testing. Preferred in the 1990s. PMID- 2315014 TI - Reaction parameters of TFIIIA-induced supercoiling catalyzed by a Xenopus laevis cell-free extract. AB - In addition to its fundamental role of nucleating the formation of stable transcription complexes, the Xenopus laevis 5S RNA specific transcription factor, TFIIIA, promotes a variety of DNA-associated metabolic reactions. We report that TFIIIA can induce a DNA supercoiling catalyzed by the Xenopus laevis S-150 cell free extract on plasmids containing a single copy of the Xenopus 5S RNA gene (somatic-type). Stimulated supercoiling occurs in the presence of high concentrations of ATP (4 mM) and at a factor to DNA ratio of 1 through a mechanism most likely involving type I topoisomerase. The highest level of stimulated supercoiling occurs when TFIIIA is incubated with DNA prior to the addition of the S-150 extract. Taken together, the experiments outlined in this report establish a reliable and seminal system in which TFIIIA-induced DNA supercoiling can be observed reproducibly. PMID- 2315015 TI - Alpha-amylase gene transcription in tissues of normal dog. AB - We studied the distribution of alpha-amylase mRNA in normal dog tissues by northern blotting (NB) and reverse transcription-polymerase chain reaction (RT PCR) with human pancreatic (AMY2) and salivary (AMY1) alpha-amylase cDNA-specific primers. Analysis of poly(A+) RNA from various normal tissues by NB indicated the presence of detectable levels of alpha-amylase mRNA transcripts only in pancreas. Dot-blot analysis of DNA amplified with primers common to both (human) isoamylase mRNAs showed presence of alpha-amylase gene transcripts not only in pancreas but also in liver, small intestine, large intestine and fallopian tube. Traces of amylase gene transcripts were also observed in ovary, uterus and lung. Interestingly, amylase transcripts were not detectable in the parotid gland by NB or RT-PCR. We have also localized alpha-amylase mRNA transcripts to dog pancreas by in situ transcription and in situ hybridization. Our results suggest that there is high degree of homology between the alpha-amylase mRNA sequences in dog and human at least in the exon 3-4 regions of the human gene. PMID- 2315016 TI - A cDNA sequence encoding a neurotoxin-homolog from Bungarus multicinctus. PMID- 2315017 TI - The sequence of the leading region of the resistance plasmid R1. PMID- 2315018 TI - cDNA deduced amino-acid sequences of two novel kappa-neurotoxins from Bungarus multicinctus. PMID- 2315019 TI - Nucleotide sequence of the mustard chloroplast genes trnH and rps19'. PMID- 2315020 TI - Sequence of the Erysiphe graminis f. sp. hordei gene encoding beta-tubulin. PMID- 2315021 TI - Satellite 1 DNA sequence from genomic DNA of the giant panda Ailuropoda melanoleuca. PMID- 2315022 TI - Nucleotide sequence of a gene encoding a 29 kDa polypeptide in mba region of the virulence plasmid, pKDSC50, of Salmonella choleraesuis. PMID- 2315023 TI - Cloning of cDNA encoding the complete precursor for bovine seminal ribonuclease. PMID- 2315024 TI - A plant-ferredoxin-like gene is located upstream of ferredoxin I gene (fdxN) of Rhodobacter capsulatus. PMID- 2315025 TI - The nucleotide sequence of major outer membrane protein gene of Chlamydia trachomatis serovar F. PMID- 2315026 TI - Conditions for generating well-resolved human DNA fingerprints using M13 phage DNA. PMID- 2315027 TI - Automated fluorescent sequencing of cosmid DNA. PMID- 2315028 TI - A simplified protocol for fast plasmid DNA sequencing. PMID- 2315029 TI - Spatial imaging of luciferase gene expression in transgenic fish. PMID- 2315030 TI - High resolution southern analysis of genomic DNA using heat denatured acrylamide gels. PMID- 2315031 TI - Extraction of cellular DNA from crude cell lysate with glass. PMID- 2315032 TI - Improved single-stranded DNA producing expression vectors for protein manipulation in Escherichia coli. PMID- 2315033 TI - Direct sequencing of double-stranded DNA PCR products via removing the complementary strand with single-stranded DNA of an M13 clone. PMID- 2315034 TI - Streptomyces promoter-probe plasmids that utilise the xylE gene of Pseudomonas putida. PMID- 2315035 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2315036 TI - A cassette containing the bar gene of Streptomyces hygroscopicus: a selectable marker for plant transformation. PMID- 2315037 TI - A theoretical investigation of the base sequence preferences of monointercalating polymethylene carboxamide derivatives 9-aminoacridine. AB - Theoretical computations are performed of the comparative binding affinities of five polymethylene carboxamide derivatives of 9-aminoacridine to a series of double-stranded hexanucleotides. The purpose of this investigation is to ascertain whether minor groove recognition of a guanine base adjacent to the intercalation site can occur, and be preferentially stabilized, for a given length of the polymethylene side chain, encompassing from n = 2 up to n = 6 methylene groups. For that purpose, several representative sequences were investigated, in which intercalation of the 9-aminoacridine chromophore occurred at a central d(CpG) or d(TpA) step. Investigated were the self-complementary sequences d(CGCGCG)2, d(GCCGGC)2, d(TATATA)2 and d(ATTAAT)2, as well as the 'mixed' sequences d(ACTAAT) .d(ATTAGT) and d(TGTATA). d(TATACA). For n = 3 up to n = 6, such a recognition was enabled only when the guanine base was located downstream of the intercalation site, i.e. with steps d(CGG) and d(TAG). It occurred by means of a bidentate interaction involving, on the one hand, H(N2) and N3 of the base, and, on the other hand, the carbonyl oxygen and the cis amino hydrogen of the terminal formamide moiety of the ligand. Because of the flexibility of the side chain, however, alternative binding modes were also found to occur competitively, involving backbone-only interactions of the side chain. On the basis of the present computations, upon binding to the sequence d(GCCGGC)2, an optimal value of n = 5 could be derived, with the corresponding acridine derivative eliciting both a significant prevalence of the bidentate over backbone only binding mode, and the most favourable energy balance within the investigated series. This privileged value of n = 5 is fully consistent with the experimental results of Markovits et al. and Gaugain et al. The very flexibility of the side chain, however, hampered any preferential recognition of a triplet sequence with a downstream guanine, such as d(CGG) or d(TAG), to be elicited over sequences such as d(TAA), d(TAT) or d(TAC). PMID- 2315038 TI - Does butylphenyl-deoxyguanosine triphosphate differentially inhibit DNA polymerase alpha and delta activities in permeabilized HeLa cells? AB - In eukaryotic cells, two enzymes, DNA polymerases alpha and delta, are thought to play major roles in DNA synthesis. I have used butylphenyl dGTP (BuPdGTP), a potent inhibitor of purified DNA polymerase alpha, to assess the relative activities of these enzymes in two permeabilized cell systems. In both instances BuPdGTP eliminated all of the activity which was sensitive to aphidicolin. However, no conditions were found where BuPdGTP preferentially inhibited the synthesis of Okazaki fragments--the presumed products of DNA polymerase alpha activity. This implies that DNA polymerase activities on the two sides of the replication fork are unable to operate independently, being just two elements of the integrated replication machinery that undertakes DNA synthesis in permeabilized cells. PMID- 2315039 TI - Detection of mutations and DNA polymorphisms using whole genome Southern Cross hybridization. AB - We report a general method for the detection of restriction fragment length alterations associated with mutations or polymorphisms using whole genomic DNA rather than specific cloned DNA probes. We utilized a modified Southern Cross hybridization to display the hybridization pattern of all size-separated restriction fragments from wild-type Caenorhabditis elegans to all the corresponding fragments in a particular mutant strain and in a distinct C. elegans variety. In this analysis, almost all homologous restriction fragments are the same size in both strains and result in an intense diagonal of hybridization, whereas homologous fragments that differ in size between the two strains generate an off-diagonal spot. To attenuate the contribution of repeated sequences in the genome to spurious off-diagonal spots, restriction fragments from each genome were partially resected with a 3' or 5' exonuclease and not denatured, so that only the DNA sequences at the ends of these fragments could hybridize. Off-diagonal hybridization spots were detected at the expected locations when genomic DNA from wild-type was compared to an unc-54 mutant strain containing a 1.5 kb deletion or to a C. elegans variety that contains dispersed transposon insertions. We suggest that this modified Southern Cross hybridization technique could be used to identify restriction fragment length alterations associated with mutations or genome rearrangements in organisms with DNA complexities as large as 10(8) base pairs and, using rare-cutting enzymes and pulse-field gel electrophoresis, perhaps as large as mammalian genomes. This information could be used to clone fragments associated with such DNA alterations. PMID- 2315040 TI - Guanine tracts enhance sequence directed DNA bends. AB - Synthetic DNA fragments were constructed to determine the effect of G tracts, in conjunction with periodically spaced A tracts, on DNA bends. Relative length measurements showed that the G tracts spaced at the half helical turn enhanced the DNA bend. When the G tract was interrupted with a thymine or shortened to one or two guanines, the relative lengths decreased. If the G tract was replaced with either an A tract or a T tract, the bend was cancelled. Replacement with a C tract decreased the relative length to that of a thymine interruption suggesting that bend enhancement due to G tracts requires A tracts on the same strand. PMID- 2315041 TI - Synthesis and properties of dithymidine phosphate analogues containing 3' thiothymidine. AB - Dithymidine-3'-S-phosphorothioate (d(TspT)) has been prepared from a 5'-O monomethoxytritylthymidine-3'-S-phosphorothioamidite (7) by activation with 5-(p nitrophenyl)tetrazole in the presence of 3'-O-acetylthymidine. The resulting dinucleoside phosphorothioite is readily oxidised to the corresponding 3'-S phosphorothioate using either tetrabutylammonium (TBA) periodate or TBA oxone and has been deprotected under standard conditions to yield d(TspT). This dithymidine phosphate analogue is comparatively resistant to hydrolysis by nuclease P1, but the P-S bond is readily cleaved by aqueous solutions of either iodine or silver nitrate. Dithymidine-3'-S-phosphorodithioate (d[Tsp(s)T]) was prepared in an analogous fashion using sulphur to oxidise the intermediate dinucleoside phosphorothioite. Absolute stereochemistry has been assigned to the diastereoisomers of d[Tsp(s)T] by comparing their physical and chemical properties to those of the dinucleoside phosphorothioates. PMID- 2315042 TI - The structure of a pre-mRNA molecule in solution determined with a site directed cross-linking reagent. AB - We describe the use of site specific psoralen (SSP) to determine the solution structure of a segment of the human beta globin pre-mRNA. In these experiments, SSP is first delivered as monoadducts to specific nucleotides in the pre-mRNA and subsequently used to form intramolecular RNA-RNA cross-links. The use of this reagent greatly decreases the number of the cross-linked products as compared to generalized psoralen cross-linking. The experiments confirm the locations of previously determined aminomethyltrimethylpsoralen (AMT) cross-links in the human precursor mRNA. In addition, new cross-links consistent with an alternative secondary structure and a small number of cross-links that represent higher order interactions have been determined. Altogether, 42 of 47 cross-links identified in this analysis can be accounted for in a small number of alternative secondary structures and higher order interactions. The site directed cross-linking technique will be useful for the precise determination of RNA secondary and tertiary structures under a variety of experimental conditions. PMID- 2315043 TI - Preservation of a complex satellite DNA in two species of echinoderms. AB - The cloning and sequencing of a tandemly arrayed repetitive DNA sequence from the sea cucumber Holothuria tubulosa has been recently described (Sainz, J., Azorin, F. and Cornudella, L. 1989. Gene 80, 57-64). We have now searched the genomes of several echinoderm species for the presence of homologous repetitive elements. A close but not identical repeated sequence has been identified in a related holothuroid, H. polii. The monomeric repeat unit is 391 bp long and has a base composition of 66.8% A and T residues, lined up in tracts of 4 nt or larger. The monomeric sequence lacks any internal subrepeat organization although it displays a substantial degree of internal redundancy in the form of inverted and direct repeats. The repeated element accounts for 0.34% of the genome which corresponds to a repetition frequency of about 0.5 x 10(5) copies per haploid complement. The intra- and interspecific homologies among monomers of the satellite DNA as derived from sequence analyses are very high, averaging 97%. The results suggest that the homogeneity of the highly reiterated DNA sequence may be attributed to evolutionary conservative trends. PMID- 2315044 TI - Protein binding elements in the human beta-polymerase promoter. AB - The core promoter for human DNA polymerase beta contains discrete binding sites for mammalian nuclear proteins, as revealed by DNasel footprinting and gel mobility shift assays. Two sites correspond to sequences identical with the Sp1 factor binding element, and a third site includes an eight residue palindromic sequence, TGACGTCA, known as the CRE element of several cAMP responsive promoters; the 5 to 10 residues flanking this palindrome on each side have no apparent sequence homology with known elements in other promoters. Nuclear extract from a variety of tissues and cells were examined; these included rat liver and testes and cultured cells of human and hamster origin. The DNasel footprint is strong over and around the palindromic element for each of the extracts and is equivalent in size (approximately 22 residues); footprinting over the Sp1 binding sites is seen also. Two potential tissue-specific binding sites, present in liver but not in testes, were found corresponding to residues -13 to 10 and +33 to +48, respectively. Protein binding to the palindromic element was confirmed by an electrophoretic mobility shift assay with the core promoter as probe. Binding specificity of the 22 residue palindromic element, as revealed by oligonucleotide competition, is different from that of AP-1 binding element. Controlled proteolysis with trypsin was used to study structural properties of proteins forming the mobility shift bands. Following digestion with trypsin, most of the palindrome binding activity of each extract corresponded to a sharp, faster migrating band, potentially representing a DNA binding domain of the palindrome binding protein. PMID- 2315045 TI - Mammalian mitochondrial endonuclease activities specific for ultraviolet irradiated DNA. AB - Mitochondrial forms of uracil DNA glycosylase and UV endonuclease have been purified and characterized from the mouse plasmacytoma cell line, MPC-11. As in other cell types, the mitochondrial uracil DNA glycosylase has properties very similar to those of the nuclear enzyme, although in this case the mitochondrial activity was also distinguishable by extreme sensitivity to dilution. Three mitochondrial UV endonuclease activities are also similar to nuclear enzymes; however, the relative amounts of these enzyme activities in the mitochondria is significantly different from that in the nucleus. In particular, mitochondria contain a much higher proportion of an activity analogous to UV endonuclease III. Nuclear UV endonuclease III activity is absent from XP group D fibroblasts and XP group D lymphoblasts have reduced, but detectable levels of the mitochondrial form of this enzyme. This residual activity differs in its properties from the normal mitochondrial form of UV endonuclease III, however. The presence of these enzyme activities which function in base excision repair suggests that such DNA repair occurs in mitochondria. Alternatively, these enzymes might act to mark damaged mitochondrial genomes for subsequent degradation. PMID- 2315046 TI - Rapid repair kinetics of pyrimidine(6-4)pyrimidone photoproducts in human cells are due to excision rather than conformational change. AB - UV-induced pyrimidine(6-4)pyrimidone photoproducts in DNA of mammalian cells are apparently repaired much more rapidly than cyclobutane dimers. Since only immunological assays for (6-4) photoproducts have been sensitive enough for repair measurements, it was possible that these apparently rapid repair kinetics reflected a change in physical conformation of antibody-binding sites, resulting in epitope loss rather than excision. To discriminate between these possibilities, we developed a procedure to photochemically convert (6-4) photoproducts to single-strand breaks in UV-irradiated DNA with a background low enough to permit repair measurements. Analysis of a specific DNA sequence indicated that photoinduced alkali-labile sites (PALS) were induced with the same site-specificity as (6-4) photoproducts. Normal human and xeroderma pigmentosum (XP) variant cells rapidly excised (6-4) photoproducts measured as PALS, but little repair was seen in cells from XP complementation group A. These repair kinetics corresponded to those determined in the same samples by radioimmunoassay of (6-4) photoproducts. Thus we conclude that the rapid repair of (6-4) photoproducts observed in UV-irradiated human cells is not the result of a conformational change resulting in epitope loss, but reflects excision of this photoproduct from DNA. PMID- 2315047 TI - The effect of replication errors on the mismatch analysis of PCR-amplified DNA. AB - The mismatch analysis of PCR-amplified DNA has generally assumed the absence of artificially introduced base substitutions in a significant proportion of the amplification product. This technique, however, differs from the direct sequencing of amplified DNA in that non-specific substitutions will render a molecule useless in analysis. The expected signal-to-noise ratio is heavily influenced by several parameters viz. initial template copy number, number of replication cycles, eventual product yield and the type of experimental system adopted. Mathematical modelling can be used to optimize fragment length with respect to the method applied and suggests as yet undescribed improvements such as partial modification or cleavage to optimize signal detection. PMID- 2315048 TI - Electrophoretic behavior of d(GGAAAAAAGG)n, d(CCAAAAAACC)n, and (CCAAAAAAGG)n and implications for a DNA bending model. AB - Double stranded multimers (C2A6C2)n, (C2A6G2)n and (G2A6G2)n were prepared from chemically synthesized oligonucleotides to study the influence of sequences flanking the An tract on the curvature of DNA. All these duplexes, including polypurine.polypyrimidine one, exhibit strong retardation in polyacrylamide gel which is indicative of pronounced DNA curvature. It has been proposed previously that among the bends at the boundary with the oligo(A) tract two types should be distinguished: 5'-bends and 3'-bends (Koo et al., 1986) This distinction was deduced from different relative mobilities of two specially designed sequences having phased 5'-bends and 3'-bends, respectively. Our data indicate that the substitutions of nucleotides at both 5' and 3' boundaries of A6 tract result in comparable changes in relative mobility. Therefore, for B-B' bends it is important to take into account not only whether they are at the 5' or 3' end of an oligo(dA) tract, but also the particular sequences at the boundaries of this tract. PMID- 2315049 TI - Polymerase chain reaction based assay to detect allelic loss in human DNA: loss of beta-interferon gene in chronic myelogenous leukemia. AB - We have developed a polymerase chain reaction (PCR) based technique to detect allelic loss. In this differential PCR a target gene and a reference gene are coamplified in the same reaction vessel. The ratio of the intensity of the two resultant bands is an indication of relative gene dosage. This procedure is sensitive in that gene copy ratios of 2:1 and 3:2 (reference: target gene) can readily be detected. Using this differential PCR, we have examined 64 cases of chronic myelogenous leukemia (CML) for the loss of the beta 1-interferon gene, a relatively common event in certain human leukemias and lymphomas. Only one patient who was Philadelphia chromosome positive and who was in blast crisis exhibited allelic loss of the beta-interferon gene. Thus despite deletions at the beta-interferon locus in the CML cell line, K562, this perturbation is rarely seen in primary CML samples. PMID- 2315050 TI - Revising the Policy and Procedure Manual. PMID- 2315051 TI - Perinatal home visiting returns. PMID- 2315052 TI - Political subversion on Ninth and P? PMID- 2315053 TI - Expanded consciousness. PMID- 2315054 TI - U.S. embargo on health care literature. PMID- 2315055 TI - Caring as skill. PMID- 2315056 TI - Tenure turmoil: light or shadows? PMID- 2315057 TI - The moral failure of the patriarchy. AB - The present health care system operates within a larger structure that now has to be openly acknowledged as patriarchal: Caring is viewed as women's work, which is not valued and which is considered less important than the work of men. The moral failure of this worldview is evident in such health care crises as care of the homelessness and those with AIDS, and dramatic rises in rates of infant mortality among the poor. This failure demands a health care revolution--a revolution in the sense that society must give up that which no longer works. PMID- 2315058 TI - Uncovering hidden caring. AB - The characteristics of caring nursing practice are often, by their very nature, hidden. If caring is to become a core value of the health care system, these caring characteristics need to be uncovered so that they can be taught, rewarded, and recognized as contributing to successful patient outcomes. PMID- 2315059 TI - Caring as a value in nursing education. AB - Nursing educators are torn between producing graduates who are employable in the health care marketplace and educating nurses who are capable of transforming the health care system. One way to resolve this conflict is to make caring a core value in the "hidden curriculum"--the way students are taught to think and feel as nurses. PMID- 2315060 TI - Re-claiming our communities. AB - Homelessness, increases in infant mortality, Supreme Court decisions against abortion and affirmative action, and corruption among housing officials are all aspects of the patriarchal control of society that is destroying the health of individuals and communities. Nursing must assume a leadership role not only in offering new ways to structure health care, but in reordering the values of society as a whole. PMID- 2315061 TI - Identifying nursing's future leaders. AB - Only a very small percentage of registered nurses actively participate in organized nursing. Does encouraging students to participate in professional organizations lead them to participate after graduation? This study suggests that it does, but there are other factors as well. PMID- 2315062 TI - A classification of nursing technology. AB - In the previous issue, the authors described the process of technology assessment and its implications for nursing. In this article, the authors propose a classification system for nursing technology. They argue that, in the face of competition from other, rapidly proliferating health care professions, such a system is necessary to insure that nurses are acknowledged and adequately compensated for the functions they actually perform. PMID- 2315063 TI - Selected list of nursing books and journals. AB - This, the 1990 update of notable nursing books and journals, shows many new titles in the areas of nursing diagnosis, critical care nursing, pharmacology, and psychiatric nursing. Nurses and librarians will find the entire list a useful tool in developing a collection of current nursing literature. PMID- 2315064 TI - Adolescent reactions to sibling death: perceptions of mothers, fathers, and teenagers. AB - Fourteen families in which a child had died participated in this study; the mother, father, and one teenager from each family were interviewed. All participants completed a sibling bereavement inventory consisting of 109 scaled items that measured self-concept perceptions and grief reactions. The teenagers completed the inventory in terms of their own reactions; the mothers and fathers were instructed to complete the inventory as they anticipated their teenager would answer it. Mothers held significantly different views of their teenagers' self-concept and grief than did the fathers or the teenagers. Fathers' responses resembled those of their teenagers. In addition to accenting the need to study more fully the family dynamics involved when a child dies, the results call into serious question commonly held views regarding the accuracy and reliability of mothers' perceptions of bereaved children. The results suggest that more credence be given to fathers' observations about the phenomena of bereavement engaging their teenage children. PMID- 2315065 TI - Nurses' job satisfaction: a proposed measure. AB - Thirty-three items originally developed to measure three dimensions of nurses' job satisfaction were subjected to a series of checks designed to determine the number of dimensions being measured and the reliability and validity of the measures of these dimensions. Although the hypothesis of only three dimensions was not supported, the eight interpretable factors that did emerge could meaningfully be placed within these three dimensions. The eight factors were satisfaction with extrinsic rewards, scheduling, family/work balance, co-workers, interaction, professional opportunities, praise/recognition, and control/responsibility. Internal consistency and test-retest reliabilities are reported, as well as checks for criterion-related and construct validity. PMID- 2315066 TI - Treating ordinal scales as interval scales: an attempt to resolve the controversy. PMID- 2315067 TI - Focus groups: a research technique for nursing. PMID- 2315068 TI - Publish and perish. PMID- 2315069 TI - Changes in functional status after childbirth. AB - Changes in functional status after childbirth were examined over a 6-month postdelivery period in 97 women who had delivered healthy full-term infants. Functional status was defined as the woman's readiness to assume infant care responsibilities and resume her usual activities. Functional status was found to improve steadily from 3 weeks to 3 months postpartum, but no statistically significant changes were found between 3 and 6 months. However, by 6 months postpartum 6% of the women had not yet fully assumed the desired or required level of infant care responsibilities, nearly 20% had not yet fully resumed usual levels of household activities, 30% had not fully resumed usual levels of social and community activities, and more than 80% had not yet fully resumed usual self care activities. Of the 57 women who had returned to work or school by 6 months postpartum, over 60% had not fully resumed their usual level of occupational activities. Canonical analysis revealed that different sets of health, psychosocial, family, and demographic variables were associated with functional status at each data collection point. PMID- 2315070 TI - Predictors of family functioning eight months following birth. AB - A theoretical causal model was tested to determine the effects of stress on family functioning for four groups of parents at 8 months postpartum. High-risk women who had been hospitalized during pregnancy, their partners, low-risk women, and their partners were tested to find how predictors might differ by gender and risk-status. The proposed theoretical model had low predictive power among the four groups (20% to 24%); however, the exploratory, empirical models had moderate to strong explanatory power (33% to 58%). Depression had direct effects on family functioning among all four groups in the theoretical model, but the respecified models had direct effects only among the two groups of women. Antepartal stress in the form of negative life events stress had indirect effects on women's family functioning, as was hypothesized, but not for men. High-risk men's partners' pregnancy risk had direct effects on family functioning at 8 months, indicating long-term effects on the family of a high-risk pregnancy. PMID- 2315071 TI - Impact of caretaker stress on behavioral adjustment of very low birth weight preschool children. AB - The impact of caretaker daily stress and life strain on the behavioral adjustment of very low birth weight (VLBW less than or equal to 1,500 grams) preschool children was investigated; the degree to which the caregiving environment contributes to the effects of caretaker stress on child outcome was also explored. Subjects were 39 VLBW children (mean birth weight = 1,208 grams) and their primary caretakers, the majority of whom were their biological mothers. Data on caretaker stress and life strain, the caregiving environment, and child behavior were gathered when the children were 60 months of age. The impact of caretaker daily stress and life strain on VLBW child adjustment was moderate and similar to that of normal birth weight (NBW) children. The impact of caretaker stress appeared to be affected by the quality of the caregiving environment. Analysis showed that more behavior problems were found in VLBW 5-year-olds than expected in the general preschool population. Caretakers of VLBW 5-year-olds experienced more intense daily stress than those of NBW children. PMID- 2315072 TI - Breast-feeding problems in the first week postpartum. AB - Pre- and perinatal variables commonly found to predict breast-feeding duration were examined to see whether they also predicted breast-feeding problems in the first week postpartum. One hundred and twenty-eight families who prenatally committed to breast-feeding for at least 6 weeks comprised the sample. The families were randomly assigned to one of two groups: a group in which bottle feedings would be avoided in Weeks 2-6 postpartum and a group in which approximately one bottle per day would be given during the same period. Breast feeding events most commonly experienced as problems in previous studies were also reported by mothers in this sample. Multiple regression analyses revealed that bottle use in the hospital, lower satisfaction with first breast-feeding, and group assignment were weakly predictive of the Breast-feeding Problem Score at 1 week, R2 = .154, p = .0004. The negative effect of hospital bottle use was greater for women in the bottle-restricted group than for women in the planned bottle group. PMID- 2315073 TI - Predicting breast self-examination using the theory of reasoned action. AB - The personal and normative influences on breast self-examination (BSE) behavior in older women were examined using the Theory of Reasoned Action. The sample consists of 93 volunteers ranging in age from 52 to 90 years. A structured questionnaire was used for data collection. Direct and indirect measures of attitude and social norm were used to predict intention to perform BSE and BSE frequency. Contrary to the model assumptions, indirect measures accounted for more variance in both intention and behavior, and explained actual behavior better than intention to perform. Both the indirect and direct measures of attitude and social norm explained a significant amount of the variance in intention and BSE frequency. There were significant differences on all the model components (direct and indirect measures of attitude, social norm, and intention) between frequent and infrequent BSE performance groups. Discriminant analysis using the indirect measures of attitude and social norm correctly classified 76% of the women into frequent and infrequent performance groups. PMID- 2315074 TI - Ogre or 'gentle giant'? PMID- 2315076 TI - Nappy wars. PMID- 2315075 TI - PREPP-aring the future. PMID- 2315077 TI - Danger in the medicine chest. PMID- 2315078 TI - A ray of hope. PMID- 2315079 TI - Mental health. A pill for every ill. PMID- 2315080 TI - Right ventricular infarction. PMID- 2315081 TI - Setting standards. Tackling incontinence. PMID- 2315082 TI - Nursing around. Happy alternatives. PMID- 2315083 TI - Agents of change. PMID- 2315084 TI - Self-help with support. PMID- 2315085 TI - Semi-permeable film dressings. PMID- 2315086 TI - An understanding profession. Interview by Dalani Carlisle. PMID- 2315087 TI - NHS nursing homes. PMID- 2315088 TI - Domestic staff on the ward team. PMID- 2315089 TI - Awareness of teratogens. PMID- 2315090 TI - Nurse education. Issues: Competency scoring. PMID- 2315091 TI - Child health. Building for the future. The rights of the child. PMID- 2315092 TI - Child health. Building for the future. The case for paediatric nurses. PMID- 2315093 TI - Symptom care of the child with cancer. PMID- 2315094 TI - Are nurses who say they are too busy afraid to touch their patients? PMID- 2315095 TI - Child's play. PMID- 2315096 TI - Let the patients know. PMID- 2315097 TI - Beds of the future? PMID- 2315098 TI - Aid for the AIDS children. PMID- 2315099 TI - Who is an expert on ethics? PMID- 2315101 TI - Essentials of management. Motivate yourself. PMID- 2315100 TI - Essentials of management. Know yourself. PMID- 2315102 TI - Community: pensioner power. PMID- 2315103 TI - Mental health: treat with caution. PMID- 2315104 TI - Setting standards. Steps to self-medication. PMID- 2315105 TI - Look before you leap. PMID- 2315106 TI - 'The lovely lady in the third bed'. PMID- 2315107 TI - Management. Vain aspirations. PMID- 2315108 TI - Effective education. PMID- 2315109 TI - Mattress conditions. PMID- 2315110 TI - Facing the fax. PMID- 2315111 TI - Systems of life No. 181. Senior systems--46. Older patients and their medication. PMID- 2315112 TI - Mental health. Revealing hidden fears. PMID- 2315113 TI - Mental health. Joyful strategies. PMID- 2315114 TI - Quest for quality. PMID- 2315115 TI - The ultimate choice. PMID- 2315116 TI - RCN congress. 'Poacher turned gamekeeper'. PMID- 2315117 TI - 'Not the sort of thing people normally discuss'. PMID- 2315119 TI - Last rights. PMID- 2315118 TI - Missing managers. PMID- 2315120 TI - Suffer the little children. PMID- 2315121 TI - Into Europe: 1992 and all that. PMID- 2315122 TI - Nursing in Germany--dead end job? PMID- 2315123 TI - Nursing in Spain--times of change. PMID- 2315124 TI - Setting standards--improving intensive care. PMID- 2315125 TI - Expert handling. PMID- 2315126 TI - Nursing children in Canada. PMID- 2315127 TI - Essentials of management: support yourself. PMID- 2315128 TI - Eating disorders. To eat or not to eat? PMID- 2315129 TI - Mental health--reward and punishment. PMID- 2315130 TI - All you ever wanted to know about ... counselling. PMID- 2315131 TI - Midwives' Journal. Preparing for a home birth. Guidelines for the independent midwife. PMID- 2315132 TI - Midwives' Journal. Going independent. PMID- 2315133 TI - Midwives' Journal. Advising on alcohol. PMID- 2315134 TI - Midwives' Journal. Self-help in Central America. PMID- 2315135 TI - Ceausescu's legacy. PMID- 2315137 TI - A dream job? PMID- 2315136 TI - Heard but rarely heeded. PMID- 2315138 TI - Spreading the load. PMID- 2315139 TI - Falling off cloud nine. PMID- 2315140 TI - Primary nursing. A network for change. PMID- 2315141 TI - Primary nursing. Learning from experience. PMID- 2315142 TI - Primary nursing--current research. Applications in ICU. PMID- 2315144 TI - No conferring. PMID- 2315143 TI - Redress sense. PMID- 2315145 TI - Does work make you sick? PMID- 2315146 TI - Trapped in a stammer. PMID- 2315147 TI - A model home? PMID- 2315149 TI - Money rights. Patients at home. PMID- 2315148 TI - As other sees us. Emotional support. PMID- 2315150 TI - Bereavement support. PMID- 2315151 TI - Systems of life No. 180. Senior systems--45; Mental health and illness in old age -3. PMID- 2315152 TI - A.C.A. Continence. PMID- 2315153 TI - Continence: combining resources. PMID- 2315154 TI - Continence: update on eric. PMID- 2315155 TI - Prediction of AIDS cases. Pattern of AIDS increase. PMID- 2315156 TI - Caring views on AIDS. PMID- 2315157 TI - Who prescribes? PMID- 2315158 TI - The cost of learning. PMID- 2315159 TI - Many happy returners? PMID- 2315160 TI - Fatal reaction. PMID- 2315161 TI - The times they are a-changing. PMID- 2315162 TI - A photo opportunity. PMID- 2315163 TI - A matter of life and death. PMID- 2315164 TI - Testicular self-examination. PMID- 2315165 TI - Education. Window on achievement. PMID- 2315166 TI - Psychiatric. Treated like human beings. PMID- 2315167 TI - Fair deal on appeal. How can we manage? PMID- 2315169 TI - A smarter way of nursing? PMID- 2315168 TI - Dual-purpose midwifery. PMID- 2315170 TI - Computer-assisted care planning. PMID- 2315171 TI - Computer control. PMID- 2315172 TI - Trauma. PMID- 2315173 TI - Care of the multiple trauma victim. The first hour. AB - Trauma is a devastating event that affects all ages. Trauma can be fatal, disabling, or disfiguring. Public awareness, education, and legislation can affect the trauma statistics of the future. Health professionals such as nurses are working toward these goals, but government and community support is also needed. If 24 per cent of trauma deaths can be prevented when appropriate medical and nursing care is provided within the first hour after injury, then health professionals and hospitals, as well as communities, are obligated to provide a system that makes "appropriate" care available. Appropriate care involves a team approach including prehospital personnel, nurses, physicians, and ancillary services, all trained in performing primary and secondary assessments. Appropriate care also includes immediate treatment of life-threatening injuries and shock during the first hour. Nurses are key members in this team approach. By utilizing assessment skills, nursing diagnosis, interventions, and constant evaluation, the trauma nurse will contribute to the decrease in preventable deaths during the first hour. PMID- 2315174 TI - Nursing care of the pediatric multitrauma patient. AB - Pediatric multitrauma causes more deaths and injuries each year in children than any other cause of death. Most of the multitrauma cases involve a motor vehicle accident. Blunt trauma and head injuries constitute the majority of injuries in pediatric multitrauma. Blunt trauma leaves minimal evidence of the underlying injury and is difficult to assess in the unconscious child. The initial assessment in children is in some ways more complex than in an adult. The airway is a more critical concern in the child. Airway obstruction is a more frequent cause of ventilatory insufficiency in pediatric trauma. Hypothermia is a vital concern because children lack the ability to maintain their temperature when they are compromised. Assessment of circulation and shock in children is complicated because the signs of shock are subtle in the child. The plan of care and the approach to the child must incorporate the child's fears and coping mechanisms based on the child's age and developmental level. Nursing diagnoses should reflect the plan of care not only for the child, but for his or her family. The proper approach to the child can positively influence the quality of the assessment, the level of cooperation, and the long-term outcome of care. PMID- 2315175 TI - Ethical dilemmas in trauma nursing. AB - For someone seeking to understand the ethical dimensions of trauma nursing, it quickly becomes apparent that there is a uniquely complex set of issues to be examined in this context. Many of these issues are made more difficult by the fact that the provider/patient relationship that undergirds the moral dimension of patient care in other contexts is necessarily truncated or absent in the trauma unit. This article seeks to explore some of these issues and the moral ambivalence they create. PMID- 2315176 TI - The family of the trauma victim. AB - Emergency room and trauma unit work offers unique challenges to the nurse, both professionally and personally. One of these challenges is understanding and dealing with the behavior of victims' families. Some of the factors that impact on the behavior of families include (1) the sudden and unpredictable nature of trauma; (2) the nature of the relationship of the specific family member and the trauma victim; (3) the issues of responsibility, anger, and guilt; (4) religious beliefs; and (5) trauma sequelae. The development of organ and tissue donor programs and of psychotraumatology as ways to help ease the plight of trauma victims' families are also discussed. PMID- 2315177 TI - Wound healing. PMID- 2315178 TI - Emergency department nursing management of patients with orthopedic fractures resulting from motor vehicle accidents. AB - Nursing management of patients with orthopedic fractures resulting from motor vehicle accidents is a frequent challenge for nurses in an emergency department setting. The nurse must have knowledge of the mechanics of injury, the classification of the resulting fracture types, and the usual medical interventions. In addition, emergency department nurses should follow plans of care that are based on nursing diagnoses so that appropriate nursing interventions can be determined and consistently provided. Initiation of these care plans must not be delayed until the patient is admitted to an inpatient nursing unit, but should be begun in the emergency unit setting. This article presents information that the emergency room nurse needs in order to make plans for nursing care, and discusses seven nursing diagnoses that are almost always appropriate for patients seen in the emergency department who are experiencing orthopedic fractures resulting from motor vehicle accidents. PMID- 2315179 TI - "A small coalition of antismoking zealots"--look what they did! PMID- 2315180 TI - Managing VAD withdrawal occlusion. PMID- 2315181 TI - Prevention of pressure sores in patients with cancer. AB - Pressure sores can lead to life-threatening infection in people with cancer. Identifying patients at risk is of prime importance in instituting appropriate preventive regimens before pressure sores develop. Pressure can be reduced through use of soft bedding, by turning the patient at frequent intervals to the 30 degree oblique angle, increasing mobility, enhancing nutrition, and reducing moisture and friction. Patient assessment, teaching, and measures to reduce pressure, prevent shearing forces, and prevent maceration from moisture and friction are addressed in a protocol. PMID- 2315182 TI - Nursing care of patients receiving activated lymphocytes. AB - Activated lymphocytes are administered to patients as a component of many biological therapy clinical trials. Oncology nurses caring for these patients need to understand administration techniques, potential side effects, and management strategies. Activated lymphocytes may be administered intravenously or regionally; administration techniques and side effects differ depending on the route of administration. The major side effects with intravenous infusion are chills/rigors, fever, hypotension, tachycardia, respiratory compromise, headache, nausea, and vomiting. When activated lymphocytes are infused regionally, the most common side effects are immediate regional discomfort and delayed chills, fever, and hypotension. Management of these side effects involves intense nursing care including assessment, monitoring, and interventions to promote medical stability and symptom control. Astute assessment skills and sound nursing judgement are essential for the safe administration of activated lymphocytes. PMID- 2315183 TI - Magnetic resonance imaging and the implantable port. AB - Magnetic resonance imaging (MRI) is a promising noninvasive procedure in cancer detection, producing images without using ionizing radiation. Since the heart of the MRI is a large magnet, certain metals such as stainless steel can cause artifacts in the images. Depending upon its composition, the presence of a metal implantable port could interfere with this diagnostic procedure. Manufacturers of metal ports recommended that the port not be exposed to the magnetic field. High grade titanium ports reportedly produce minimal artifacts, and those of nonmetal materials reportedly produce no artifacts. Knowing which metal ports are acceptable is important, but because of the wide spectrum of proprietary steels used in port manufacture, healthcare professionals may not know the metal type unless the manufacturer provides this information and it is recorded in the medical record. With the increased use of both implantable ports and MRI, healthcare professionals need to know which type of port is implanted and its possible effects on MRI. PMID- 2315184 TI - A model of continuing education for rural oncology nurses. AB - Societal changes from an industrial era to an informational era create an ever increasing demand for adult continuing education. Malcom Knowles (1970) proposed a theory of adult learning; del Bueno later applied these principles to a model she described as competency-based nursing education. This article considers these two models and describes an innovative, cost-effective, continuing education model developed by a group of oncology nurses in one rural state. This model was one strategy to address their continuing learning needs. PMID- 2315185 TI - Recovering from cancer: a nursing intervention program recognizing survivorship. AB - The Oncology Nursing Task Force of the Cleveland Clinic Cancer Center and the local county unit of the American Cancer Society jointly sponsored "EXPO '88: Recovering from Cancer" on the first National Cancer Survivors' Day held on June 5, 1988. The event--a day of survivor recognition and celebration, education, and support-provided a setting for oncology nurses to participate in a program recognizing cancer survivorship and enhancing awareness of survivors' issues. Program goals, development, planning, evaluation, and implications for nursing are discussed. PMID- 2315186 TI - The impact of the cancer experience on long-term survivors. AB - Little is known about the impact of the cancer experience on long-term survivors of adult cancers. This exploratory study describes survivors' needs and identifies emic (in the subject's own words) categories and patterns among physiological, psychological, and socioeconomic changes, problems/concerns, and needs. A purposive sample of 17 adults more than two years post-cancer therapy was interviewed using the semi-structured Cancer Survivor Questionnaire (CSQ). Deductive content analysis was used to identify specific changes, problems/concerns, or needs associated with physiological, psychological, and socioeconomic categories. Inductive content analysis identified major emic themes and patterns. Findings indicate that the cancer experience permanently changes life patterns and suggest guidelines for nurses to use in helping the cancer survivor better adapt holistically to long-term survival. PMID- 2315187 TI - The death surround: factors influencing the grief experience of survivors. AB - Factors surrounding the death of a loved one can have a profound impact on the grief experience of survivors. This study examined the relationship between participation in a hospice program of care, place of death, length of illness prior to death, and the grief experience of survivors of patients who have died of cancer. Sixty survivors responded to the Grief Experience Inventory (GEI). Survivors of terminally ill people who participated in a hospice program prior to the death showed decreased feelings of guilt, dependency, loss of control, despair, numbness, shock, and disbelief. Survivors of those who died in the home had fewer guilt feelings and decreased death anxiety, but showed greater social isolation tendencies and were more apt to dwell on thoughts of the deceased. Finally, survivors of those who were ill six months or less had a greater need for dependency on others, isolated themselves more, and had increased feelings of anger and hostility. Study findings have significant implications for providing a death surround that enables an appropriate death for the patient and adaptation of the family that can lead to a more successful bereavement for survivors. PMID- 2315188 TI - The patient with testicular cancer: nursing management of chemotherapy. AB - Although testicular cancer accounts for only one percent of all male malignancies, it affects a predominantly young population (15-35 years). Despite its relatively low incidence, the emotional, financial, and psychosocial implications of the disease and its treatment in this young population are enormous. Knowledge of the disease and its treatment-related side effects and toxicities is essential to planning comprehensive nursing care. This article reviews the natural history, treatment, and nursing management of the client with testicular cancer, focusing on the specific and most current issues associated with this disease and its chemotherapeutic treatment. Application of research findings in the management of both short- and long-term sequelae are discussed. PMID- 2315189 TI - Decreasing documentation time using a patient self-assessment tool. AB - A 1986 audit of 150 randomly selected radiation therapy patient records revealed 147 records containing completed nursing assessment and weekly progress notes. Documentation of care provided was comprehensive, but concern was expressed over the length of time it required--an average of 40 minutes for the patient interview and an additional 20 minutes for documentation. Two strategies were proposed to reduce the amount of time spent in documentation without jeopardizing the detail of information contained in the initial nursing assessment: to pilot a patient self-assessment tool based on our original functional health pattern nursing assessment and to develop a standard flow sheet that contained both frequently used nursing diagnoses and potential interventions. Selected patients completed self-assessment records and discussed them with their primary nurses on the first day of treatment. Based on the pilot data, the forms were modified and revised. In 1987, 50 revised patient self-assessment records were reviewed revealing that both subjective and objective information had improved. Documentation time was reduced and information was more comprehensive. PMID- 2315190 TI - Preparing patients with breast cancer for brachytherapy. PMID- 2315191 TI - AIDS education: a community hospital approach. PMID- 2315192 TI - Maximizing caloric intake. PMID- 2315193 TI - Controlling nausea and vomiting in outpatients. PMID- 2315194 TI - The challenge of research on international populations: theoretical and methodological issues. PMID- 2315195 TI - Relationship between values of bioelectrical impedance and creatinine clearance. AB - This investigation was conducted to determine if measurements of bioelectrical impedance in conjunction with serum creatinine concentrations are useful in predicting creatinine clearance. Twenty-eight healthy volunteers between 23 and 50 years of age followed an individualized protein diet to provide 1.2 g protein/kg/day for 3 consecutive days. At the beginning of day 3, a 24-hour urine collection was initiated. At the midpoint of urine collection, bioelectrical impedance measurements of resistance and reactance were taken, together with a single blood sample for assessment of serum creatinine concentration. Multiple linear regression techniques were used to identify significant values for predicting creatinine clearance. Resistance and serum creatinine concentration were identified as significant predictors. The measured creatinine clearance was compared to that predicted by the impedance-derived model that we developed, as well as other established estimation methods. Mean absolute prediction errors in creatinine clearance using this model were significantly lower than those obtained using four empiric methods. Bioelectrical impedance may provide a noninvasive, quick, and accurate method for predicting creatinine clearance from serum creatinine concentration values. PMID- 2315196 TI - Hepatic failure associated with imipramine therapy. AB - Imipramine, a widely used antidepressant, has rarely been associated with hepatic abnormalities. In the majority of reported cases, hepatic effects have been transient and readily reversible on discontinuation of the drug. We cared for an 11-year-old boy with hepatic failure and massive cell necrosis which followed treatment with imipramine for enuresis. This therapy led to fulminant hepatic failure and subsequent liver transplantation. PMID- 2315197 TI - The impaired psychiatrist. AB - Precise data on impaired psychiatrists is lacking, but the evidence suggests significant prevalence due to mental illness, substance abuse, and personality disorder. The complexity and stress of the profession may induce and aggravate vulnerabilities that lead to impaired functioning. Although the very idea of impaired function centers on harmful patient care, colleagues may be affected in ways that, via transference reactions, are not always helpful. There is a great need to balance sanction and rehabilitation, and we need to be proactive and research oriented in dealing with the problem. PMID- 2315198 TI - Improving quality. PMID- 2315199 TI - Promoting quality assurance through performance contracting. AB - Performance contracting is an essential component of quality assurance in human service settings. Performance contracting involves developing performance standards for administrative, support service, and direct service personnel; communicating and contracting with personnel to ensure that they agree to comply with the performance standards for their positions; and using standards to monitor and evaluate the quantity and quality of staff performance. Performance contracting also serves to reinforce organizational structure and facilitate program evaluation and is useful in helping to ensure that psychiatrists and other professionals are sufficiently committed to meeting organizational goals as well as those of their professional disciplines. PMID- 2315200 TI - Risk management in psychiatry. AB - This article introduces some basic concepts of psychiatric risk management and demonstrates how risk management and quality assurance can work together. Risk exposure areas and loss prevention issues identified during a review of 98 psychiatric claims managed from 1976 to 1988 by the Risk Management Foundation of the Harvard Medical Institutions are detailed. PMID- 2315201 TI - Linking utilization management with quality improvement. AB - The author describes the context for conducting utilization management and quality improvement studies in psychiatry; utilization management and quality improvement are defined and differentiated. Examples of utilization management and drug utilization evaluation studies are given with explanation of how they can be linked to quality improvement efforts. PMID- 2315202 TI - A collaborative approach to clinical standards development. Psychiatry and psychiatric nursing in a changing world. AB - Today's consumers, faced with limited resources, want documented proof of the quality of a product or service. This shift to consumerism has caused health care providers and institutions to carefully examine their practice and move toward the establishment of standards of care in all areas. The authors are recommending a collaborative approach between standards and are advocating the use of the Marker Model as a system to define, organize, integrate, document, and monitor standards in the fields of psychiatry and psychiatric nursing. PMID- 2315203 TI - Quality improvement: a collaborative discipline approach. AB - In order for a quality assurance program to achieve its goal of true quality improvement, it must function in full partnership with the entire treatment team as a collaborative discipline. It must actively contribute to the care by not only developing effective studies and reports on treatment but also must share these results in an educational, timely, relevant, and individualized manner. This article offers a number of specific methods to enhance staff involvement and participation in quality assurance and describes a series of collaborative approaches and techniques to promote their collaboration. PMID- 2315204 TI - Introducing quality assurance to a state hospital medical staff. AB - Establishing a quality assurance program in a developing state hospital requires considering the unique problems of being a physician in such a setting. The hospital and medical staff must be developed to the point where consideration of quality of care is a feasible goal. Managers can take advantage of the interests of individual medical staff as well as serendipitous factors promoting a program. PMID- 2315205 TI - Taxpayers on the ward. Quality improvement through the Citizen Monitoring Program. AB - This chapter describes the Massachusetts Citizen Monitoring Program and discusses the program's history and rationale. Although the program has great intuitive and political appeal, little data currently exists with which to assess its effectiveness in improving patient care. The monitoring and evaluation model of the Joint Commission on Accreditation for Healthcare Organizations is proposed as an alternative to the present program. Under the proposed model, the program should become more efficient and effective. PMID- 2315206 TI - From quality assurance to quality improvement. AB - As we are learning to master the methods of quality assurance, a new conceptual approach focused on quality improvement is being advocated. But this new approach is not a derailment for health care practitioners committed to improve patient care quality. Rather, it is a progressive step that builds upon the concepts and methods of quality assurance. Whereas quality assurance tends to focus on correcting problems in patient care quality--especially individual practitioners' problems--quality improvement focuses on finding opportunities to improve quality by changing systems as well as individual practitioner behavior. Whereas quality assurance tends to rely primarily on standards or guidelines for the structures and processes of care and the intensive review of individual cases with undesirable outcomes, quality improvement also utilizes statistical profiles of outcomes, structures, and processes as baselines against which improvement can be measured. Whereas quality assurance may engender defensiveness in an individual practitioner, quality improvement is based on the health care practitioner's professional ethic and pride in providing even better care to patients tomorrow than is possible today. To improve patient care quality, it is necessary to examine the structures, processes, and outcomes of care. The structures and processes can be controlled by the practitioner and organization; the outcomes are the benchmarks against which the effectiveness of the structures and processes can be evaluated. Outcomes in health care are the effects of more than just the structures and processes controlled by the practitioner and organization. Therefore, outcomes are not direct and complete measures of the quality of the care provided. They are instead indicators of performance. These indicators can focus attention on care that lies outside the normal statistical parameters of performance and can provide baselines against which improvements can be measured. The monitoring and evaluation process described in Joint Commission standards is a method for establishing priorities and using indicators to improve the quality of patient care. This method can be used to focus case based review of care and to establish baselines for continuous improvement. This conceptual approach that emphasizes quality improvement and the use of the monitoring and evaluation process is guiding the Joint Commission's development of clinical indicators and revision of its standards and survey process to help health care organizations in the transition from quality assurance to quality improvement. PMID- 2315207 TI - The consequences of tubulo-interstitial changes for renal function in glomerulopathies. A morphometric and cytological analysis. AB - Morphometric investigation of the structures of the cortex in kidneys exhibiting various types of glomerulopathy revealed the following: 1. In various types of glomerulonephritis, diabetic glomerulosclerosis, and glomerular amyloidosis there are significant correlations between the severity of fibrosis of the renal cortical interstitium and tubular atrophy resulting from chronic interstitial inflammation, and the serum creatinine concentration, creatinine clearance, inulin clearance and PAH clearance. 2. As illustrated with the example of membranoproliferative glomerulonephritis type I, if glomerulopathy alone is present, there is no elevation of the serum creatinine concentration, even if the glomerular inflammatory changes are severe; neither are severe renal amyloidosis that is confined to the glomeruli and severe isolated diabetic glomerulosclerosis associated with elevation of the serum creatinine concentration. 3. There is a significant negative correlation between the severity of interstitial fibrosis resulting from chronic inflammation and the total number and cross-sectional area of the intertubular capillaries; i.e., the total cross-sectional area and number of capillaries per unit area decrease as the fibrosis of the cortical interstitium increases. 4. Cases of glomerulonephritis in which there is accompanying fibrosis of the renal cortical interstitium have a significantly worse long-term prognosis than those in which there is only severe glomerulitis. 5. Obliteration of the post-glomerular capillaries leads to an increase in the cross-sectional area of the glomerular capillary convolution, the morphological equivalent of an increase in intraglomerular pressure. 6. The cause of the disease of the renal cortical interstitium that may accompany the various types of glomerulonephritis is not known. It is considered possible, as a working hypothesis, that this inflammation represents a T-cell stimulated autoimmune process in which fibroblast proliferation occurs, leading to an increase in numbers of fibrocytes in the renal cortical interstitium and thus to increased production of collagen. PMID- 2315208 TI - Proliferation and maturation of human bone marrow cells in infectious diseases. AB - In 6 patients with various types of infectious disease an extended study of proliferation and maturation of erythropoiesis and granulocytopoiesis was performed. By means of quantitative 14C-autoradiography DNA synthesis time and labeling index were determined in every morphologically defined cell compartment of both lineages. With these parameters and the relative frequency of cells in the various compartments cell cycle times, relative cell production rates and maturation indices were determined. A general labeling index reduction and prolongation of DNA synthesis time was observed which was statistically significant in the majority of compartments. As a consequence, cell cycle times were prolonged throughout, the deviation from normal increasing with advancing maturation in both lineages. Relative cell production was normal in myelocytes, but elevated in myeloblasts and promyelocytes. On the other hand, proerythroblasts and basophilic erythroblasts showed normal relative cell production rates, while a significantly reduced value was found in polychromatic erythroblasts. The maturation index in both lineages was reduced by roughly 50%. Since cell cycle times were generally prolonged, the most significant deviations from normal being present in the latest proliferative compartments, the low maturation indices are discussed in the light of ineffective erythro- and granulocytopoiesis. Premature cell death in the bone marrow is suggested to be a significant factor in particular cases of infectious disease. PMID- 2315209 TI - Non-random spatial distribution of intermembraneous particles in red blood cell membrane. AB - A combined analysis using digital image processing and quantitative evaluation of computed radial distribution of freeze fracture P face particles irradiated and nonirradiated has been carried out. Important quantitative features of the arrangement of particles can be described by computing a statistical measure, the radial distribution function g(r), commonly used to study the structure of liquids. The coordinates for calculating g(r) for each sample were measured automatically by a digital image processing system. The results for the radial distribution function were found to closely resemble g(r) for fluids, indicating the presence of shortrange order. This measure distinguishes three different patterns: i) random distribution, ii) dilute gas like and iii) a liquid like model. The mean number of first nearest neighbours surrounding each particle (coordination number) was found to be of the order of three. The RBC intramembraneous particles are heterogeneous in their behavioural pattern: two thirds random; one fifth, dilute gas; and one tenth, liquid. PMID- 2315210 TI - Light and electron microscopy of the spontaneous intimal thickenings of rabbit aorta. A normal arterial wall growth. AB - A light and electronmicroscopic study in the intima of the smaller and larger curvatures of a healthy rabbit aortic arch was performed. In both curvatures there were areas of intimal thickenings of varying width, and consisting mainly of collagenous and elastic fibers and smooth muscle cells. The structure of the wider thickenings resembled the media layer. There was evidence that such intimal thickenings are media growth in thickness and physiological in nature. It is inferred that the early lipid deposition in the intimal thickenings of the smaller, but not in the larger curvature, is not related to morphological differences, since both curvatures had the same intimal pattern. PMID- 2315211 TI - Clinical and pathological changes of the heart in brain death maintained with vasopressin and epinephrine. AB - In ten brain death patients circulatory stability was attained with both vasopressin and a minimum dose of epinephrine for more than a week. Clinical and pathological changes of the heart after brain death were examined in this model. ST-T wave changes of ECG were initially observed in 57%. The required dose of epinephrine to maintain the systemic blood pressure was rather high in the first two days after brain death and could be reduced below 0.1 kg/min in a steady state. Normal level of CPK-MB in this study indicated that the damage of the heart was reversible. The cardiac biopsy specimens from the right ventricular septum were obtained serially and they showed normal or slightly swollen mitochondria. The mitochondrial scores were below 1.0 in seven patients, and they were elevated to more than 1.0 in three patients with prolonged shock. The heart of brain death was suppressed by the shock at brain death, but it could be preserved in good condition for several days with our circulatory support which uses both arginine vasopressin and epinephrine. PMID- 2315212 TI - The influence of portocaval shunting on inner ear structures. AB - In rats with a portocaval shunt the cells of the inner ear were examined in an ultrastructural study. In 15 rats a porto-caval shunt (PCS) was constructed. Control rats underwent identical procedures but no anastomosis was produced (SOP). The control rats were pair-feeded. PCS rats developed an increased urinary zinc excretion associated with weight loss, alopecia, lethargy and atrophy of the testes. The serum zinc concentration in PCS rats was significantly reduced. In the inner ear we found ultrastructurally an increasing number of lysosomes and a severe damage of the myelin sheath of the granular ganglion cells. The myelin sheath was split and filled with great myelin figures. In the outer hair cells resulted in an increasing number of lysosomes. In the stria vascularis and in Reissner's membrane a vacuolization of the tissue appeared. The results of this study show that rats with a porto-caval anastomosis serve as a pathophysiological model of zinc impoverishment like porto-caval shunting in patients with liver cirrhosis. PMID- 2315213 TI - Physiological and pathological morphology of the umbilical and placental circulation. AB - Closure mechanisms of fetal vessels are essential after birth. They are physiological. The speedy and characteristic constriction is made possible by the special construction of the fetal vessels. The so-called "folds of Hoboken" in the umbilical artery initially form tapered constrictions which quickly extend to longer sections of the vessel. The contractions continue to include the chorion plate and the villi. Due to a lack of lamina elastica interna, a protrusion of pear shaped, expanded mediamyocytes and myofibroblasts is possible which reduces the cross-sectional area of these vessels. Similar, but lasting reductions in the cross-section of the villous arteries due to a fibrous-muscular media occur in the second half of pregnancy (IVth sign of maturity). Closure of the fetal vessels during intrauterine life leads to placental insufficiency of fetal death in utero. The endarteritis obliterans closes villous vessels by means of a connective tissue plug which starts on one side of the vessel and continues across the whole width of the lumen. The periphery dependent of these villi remains avascular, as the placenta is limited in its resorptive capabilities. In the case of intrauterine asphyxia, intravasal fibrinthrombi form as a sign of subacute insufficiency in the utero-placental circulation. A decompression collapse occurs in the fetal circulation, when fetal death occurs with continuing maternal circulation. PMID- 2315214 TI - Trace metal analysis of chromium and nickel in lung tissue fixed and stored in formalin. AB - In an attempt to answer the question whether the determination of chromium and nickel concentration in lung tissue, fixed and stored in formalin is still tolerable despite the related sources of error, the entire system (tissue, tissue abrasion, formalin, plastic container) was analysed by means of flameless atomic absorption spectrometry. It appears that such a procedure can be justified for practical purposes. In order to reduce possible errors, well defined rules are to be observed during specimen collection and processing and specialities have to be taken into account. PMID- 2315215 TI - Stromal changes in early invasive breast carcinoma. An immunohistochemical, histoenzymological and ultrastructural study. AB - The purpose of this work was to detect in periductal connective tissue of breast carcinoma in situ changes induced by intraductal tumor cells before any dehiscence in basement membrane. Histological, electron microscopic, immunohistochemical and histoenzymological methods were used in 3 carcinomas in situ, 4 microinvasive carcinomas and 13 control invasive carcinomas. We could demonstrate a high functional activity of fibroblasts with secretion of mucopolysaccharides and type III collagen around intraductal carcinomas. These changes occurred simultaneously to those of the basement membrane which was either thinning or thickening. Any dehiscence in basement membrane secondarily induced in this periductal stroma the usual changes seen in invasive stroma, peculiarly numerous vascular pedicles, myofibroblasts, elastic material. These periductal stromal changes are interpreted according to recent concepts about the possible influence of tumor cells upon their environment: stimulation of mitotic and metabolic activity of fibroblasts: stimulation of angiogenesis by means of an angiogenic factor. PMID- 2315216 TI - An evaluation of gastric dysplasia in the years 1986 and 1987. AB - Since the fate and significance of gastric mucosal dysplasia is still largely unknown we have started a follow-up study for patients with dysplasia in the years 1986 and 1987. In this paper the short term results are reported. Dysplasia grade II was found in 2% of all patients and dysplasia grade III in 0.5%. The following results suggest a close-possibly sequential relationship of dysplasia and gastric cancer: dysplasia and gastric cancer are preferentially located in distal parts of the stomach; sex distribution of dysplasia and gastric cancer (especially intestinal type) are similar; considering the mean age of patients with dysplasia or gastric cancer we have observed that patients with dysplasia II were younger than patients with dysplasia III and both were younger than patients with gastric cancer of the intestinal type; during the short term follow-up (12 24 months) 4-8% of patients with dysplasia II and 18-20% of patients with dysplasia III showed a progression; of 26 carcinomas detected by follow-up of patients with dysplasia III 10 were early gastric cancer, 11 resectable with curative intent, 2 were metastatic and 3 without sufficient information for staging. We conclude therefore that gastric dysplasia is probably a true precancerous lesion that helps to identify high risk patients and thus contributes to the objective of an early diagnosis of gastric cancer. PMID- 2315217 TI - Left and right sided breast cancer. AB - Many studies have shown that unilateral breast cancer is more frequent in the left breast than in the right. This has been investigated in the Icelandic Cancer Registry. Information on all but 18 female breast cancer cases diagnosed in the forty-year-period from 1948 to 1987, a total of 2139 cases, was used. Of these 2011 were unilateral, 1069 were in the left breast, an excess of 13%. Primary breast cancer in both breasts was diagnosed in 81 women, 35 in the left breast first, and 46 in the right breast first. The excess risk of developing cancer remains for the left breast also for women who have already lost one breast because of cancer. Information on whether their relatives had developed breast cancer existed for 1197 of these women. Patients with an affected first degree relative were of 2.54 fold risk of developing contralateral primary breast cancer, but women with no affected relative were at a reduced risk (not significant). Patients with right sided breast cancer are more likely to have a relative with breast cancer. The breast cancer status of the relatives did not influence the risk of death, so a better survival of familial cases could not be shown. PMID- 2315218 TI - Extracellular matrix in preneoplastic lesions and early cancer of the lung. AB - Characterization of preneoplastic lesions mainly concentrated on cellular, nuclear and epithelial atypias. The extracellular matrix was almost neglected, although malignant tumour cells interact with extracellular matrix molecules during tumour invasion. Until now systematic investigations of extracellular matrix components in preneoplastic lesions and early stages of lung cancer are lacking. 150 preneoplastic lesions, 10 specimens of early cancer and 30 specimens of normal bronchial mucosa were examined by means of immunofluorescence microscopy. The distribution of collagen type I and III and the non-collagenous glycoproteins laminin and fibronectin have been investigated by an indirect immunohistochemical method. With an increasing degree of preneoplasia an increased matrix disarrangement of the basement membrane zone could be observed. In severe dysplasia and carcinoma in situ neosynthesis of collagen type III and especially laminin in close association to neoangiogenesis could be demonstrated besides a disintegration of extracellular matrix components. In early lung cancer numerous laminin positive basement membrane like structures are situated around tumour cells. An enhanced deposition of collagen type I and III fibres could be demonstrated around tumour cell islets. The results indicate a partial loss of function in preneoplastic basal cells in cases of dysplasia and carcinoma in situ. In early stages of invasive squamous cell carcinoma of the bronchus, extracellular matrix components obviously could be produced by tumour cells. PMID- 2315219 TI - Comparison of anterior laxity measurements in anterior cruciate deficient knees with two instrumented testing devices. AB - We measured anterior tibial displacements in 21 anterior cruciate ligament deficient patients using two instrumented testing devices, the KT-1000 and the KSS. A comparison of values obtained from testing was done using statistical analysis. The two tests common to both devices were the 20 lb pull and the manual maximum. The involved normal (I-N) values showed that there was no significant difference between the two devices for both the manual maximum and the 20 lb force level. There was also no significant difference between devices for the manual maximum absolute values. The significant difference between the absolute values for the 20 lb force level is probably due to the different testing techniques for both devices. When testing with the KSS, the patella remains free; testing with the KT-1000 requires that the examiner maintain pressure to hold the patella down. The manual maximum absolute values showed no significant difference because the testing techniques for both devices were identical. Comparable data for both devices are the I-N values for the 20 lb and manual maximum values. PMID- 2315220 TI - A quantitative assessment of degenerative changes acceptable in the unoperated compartments of knees undergoing unicompartmental replacement. AB - Thirty-five unicondylar knee arthroplasties were performed on 32 patients. In the unresurfaced compartments, degenerative cartilaginous changes were observed intraoperatively and recorded. The Outerbridge grading scale was used to assess the degree of arthritic change. In addition, the surface area involved was estimated. Grade III and limited grade IV changes in the unresurfaced tibiofemoral compartment and the patellofemoral joint did not preclude excellent results at a follow-up interval of 2 to 4 years. PMID- 2315221 TI - Early clinical experience with Orthofix external fixation of complex distal radius fractures. AB - Twelve patients with complex fractures of the distal radius were treated with the Orthofix external fixation system (EBI Medical Systems, Fairfield, NJ). On follow up physical examination, the average wrist dorsiflexion was 46 degrees, and the average volar flexion was 55 degrees. The average grip strength in the involved hand was 38 lb force. The average final radial angle was 18 degrees, and the average residual radial height was 12 mm. Average volar tilt was 3 degrees. The complication rate was 42%. Very rigid axial stability is afforded by the fixator, but the large 3.5 mm tapered bone screw diameter precludes redrilling for screw adjustment. The apparatus needs frequent monitoring to reconfirm the security of the locking nuts and cam mechanisms, and the Orthofix system can be reused only four times. PMID- 2315222 TI - Coccidioides immitis: an unusual presentation. PMID- 2315223 TI - Early surgical correction of unilateral cleft foot deformity. PMID- 2315224 TI - Bilateral piriformis syndrome associated with dystonia musculorum deformans. PMID- 2315225 TI - The magnetic resonance appearance of spinal radiation: the converse of spinal metastases. PMID- 2315226 TI - Acrocephalospondylosyndactyly--a possible new syndrome: analysis of the vertebral and intervertebral components. AB - Apert-Crouzon syndrome (formerly ACS type 2; 10130) is now considered a subset of autosomal dominant Apert acrocephalosyndactyly type 1 (10120), with features of craniosynostoisis, syndactyly of all extremities, maxillary hypoplasia, "parrot beaked" nose, hypertelorism, exophthalmos, external strabismus, and short upper lip. We report a 3 1/2-month-old infant with features of Apert syndrome, plus thoracic vertebral anomalies radiographically similar to those seen in spondylothoracic dysplasia, a condition in which block thoracic vertebrae with widely open neural arches and a fan-shaped thoracic cage are found. Our patient also had flared metaphyseal ends of humeri, dislocated radii with immobile elbows, an unusual tail-like protuberance in the coccygeal area, and a solid cartilaginous tracheal wall. To date, in ongoing reviews of radiographs of other patients with acrocephalosyndactyly or acrocephalopolysyndactyly complexes and of relevant literature, we have not identified other patients with these findings. The vertebrae and intervertebral discs of the patient in this report, three patients with Jarcho-Levin syndrome, and one with Apert syndrome were measured from anteroposterior chest radiographs; the findings clearly distinguish the condition in our patient from Jarcho-Levin syndrome or Apert syndrome. PMID- 2315227 TI - Pontocerebellar hypoplasia associated with infantile motor neuron disease (Norman's disease). AB - A Japanese female, floppy since birth, died at the age of 1 year and 10 months. Fasciculation of the tongue, neurogenic patterns on an electromyograph, and an empty posterior fossa on a cranial computerized tomogram suggested a motor neuron disorder resembling Werdnig-Hoffmann disease with cerebellar hypoplasia. Autopsy revealed a very small cerebellum and brain stem. The cerebellar cortex showed thin molecular and granular layers with total absence of Purkinje cells. Degeneration of the motor neurons with central chromatolysis, a change typical of Werdnig-Hoffmann disease, was noted throughout the anterior horn of the spinal cord as well as in the motor nuclei of the brain stem. The clinical features and pathological findings of this case were almost identical with those first detected and described by Norman in 1961. Six similar autopsy cases have been reported since the original description. In addition to pontocerebellar hypoplasia, the presence of severe mental retardation and a probable autosomal recessive inheritance make the disease a distinct entity, which we have called Norman's disease. PMID- 2315228 TI - Spontaneous regression of neuroblastoma: an experimental approach. AB - The cytolytic activity of normal pregnancy serum was first studied on murine cancer cells and shown to be the result of a natural IgM antibody that binds to cell surfaces and activates complement. Both the classical and alternative pathways of complement are involved. It was then shown that certain human neuroblastoma cell lines, to the exclusion of other human cancers, react to the same system. It is proposed that this system may play a role in the cytolytic form of spontaneous regression of neuroblastoma. PMID- 2315229 TI - Neuropeptide Y as a marker in pediatric neuroblastoma. AB - Neuropeptide Y (NPY) was investigated as a possible tumor marker in pediatric patients with tumors of the sympathetic nervous system. Seven patients with neuroblastoma, 3 patients with ganglioneuroblastoma, and 2 with ganglioneuroma, were compared with 12 matched healthy controls and 34 tumor controls. NPY-like immunoreactivity (NPYLI) was analyzed in extracted plasma using a competitive radioimmunoassay. At diagnosis, plasma NPYLI was significantly increased (p less than .001) in the neuroblastoma patients (352 +/- 99 pM; mean +/- SEM) when compared with healthy controls (36 +/- 4 pM) and tumor controls (30 +/- 2 pM). Ganglioneuroblastoma and ganglioneuroma patients had lower levels (57 +/- 8 pM) than neuroblastoma patients but still significantly higher than the controls. In all patients with sympathetic tumors, the NPYLI level was decreased after treatment. Five neuroblastoma patients relapsed; all had increasing NPYLI levels. In 3 of these patients, incresing NPYLI was the first sign of relapse. Plasma NPYLI correlated well to urinary levels of homovanillic acid. NPY in plasma (NPYLI) may be a clinically useful marker of pediatric neuroblastoma for diagnosis and differential diagnosis. NPYLI correlates well with the clinical course and can be the first sign of relapse. Plasma determinations of NPYLI make it possible to monitor rapid alterations of disease. PMID- 2315230 TI - Glomerulosclerosis in the sudden infant death syndrome. AB - In the past two decades, two groups of investigators have alleged that infants who die of the sudden infant death syndrome (SIDS) have excess numbers of sclerotic glomeruli in their kidneys. This double blind, case-control study was undertaken to test that assertion. Using microscopic sections of the kidney from 153 autopsies (99 SIDS infants and 54 control infants) in the National Institute of Child Health and Human Development (NICHD) Cooperative Epidemiologic Study of Risk Factors for SIDS, we counted relative numbers of sclerotic glomeruli in four fields of renal cortical tissue in two sections from each infant. Our results indicate that there is no difference between the two groups in regard to the proportion of sclerotic glomeruli. PMID- 2315231 TI - Clinical laboratory management: a critical evaluation. AB - The clinical laboratory is described as a system with an enquiry component or demand side, where control of test utilization is the mandate of the clinical physician or surgeon, and a production component or supply side, where answers to clinical questions are generated and control of test data production is the mandate of the laboratory physician. Supply side unit costs are maintained by increased production effectiveness brought about by the judicious manipulation of supply costs; labor costs; and capital expenditures for automated equipment, robots, and information technologies. The pathologist's prime role as controller of the supply side is outlined, as are the clinical physician's prime role and pathologist's subsidiary role in control of test use on the demand side. PMID- 2315232 TI - Mesodermal cell determination and differentiation. AB - Many in vitro systems have been designed to study the processes governing cell determination and differentiation during development. Mammalian culture systems have been particularly helpful in elucidating the mechanisms regulating gene expression during differentiation in cells of mesodermal origin, namely, myoblasts, preadipocytes, and chondroblasts. Studies have shown that particular cis-acting sequences and trans-acting factors are important in determining tissue specific and developmental gene expression in these systems. The role of growth factors, oncogenes, and other agents during differentiation has also been examined. Recently four putative muscle determination genes have been isolated and are being characterized. These studies have been useful in postulating models of how development proceeds in vivo and how differentiation and transformation to a neoplastic phenotype may be related. PMID- 2315233 TI - Development and transformation of the ductal plate in the developing human liver. AB - The livers of 15 embryos and fetuses measuring from 0.5 cm to 21 cm in crown-rump length were examined. The liver of the smallest embryo showed a sheet of hepatocytes without any ductal plates or intrahepatic bile ducts. Transformation of the hepatocytes of a hilar ductal plate was first observed in a 1.8-cm embryo. A 10.0-cm fetus had ductal plates virtually throughout the liver. Focal transformation of the flattened cells of the ductal plates into tubules composed of columnar or cuboidal ductal cells was observed. Mature interlobular ducts were observed predominantly in the hilum whereas scattered primitive interlobular ducts were scattered throughout the parenchyma. The transformation of hepatocytes into interlobular bile ducts thus seemed to occur in two stages: in the first, the hepatocytes of the ductal plate became flattened and developed increased cytokeratin; in the second, these flattened cells became focally cuboidal or columnar, lost their carcinoembryonic antigen, became strongly positive for epithelial membrane antigen, and formed tubules and primitive interlobular bile ducts. PMID- 2315234 TI - Confined placental mosaicism and intrauterine development. AB - Confined placental chromosomal mosaicism can be detected in 1-2% of pregnancies studied by chorionic villus sampling at 9-12 weeks of gestation. It is more commonly found in the cytotrophoblast than in placental connective tissue. Aneuploid conceptions are more likely to have confined chromosomal mosaicism than euploid ones. Although intrauterine survival of chromosomally abnormal embryos and fetuses appears to be significantly enhanced by placental mosaicism, the effect of placental mosaicism on chromosomally normal fetuses is variable and, at the present time, still unpredictable. PMID- 2315235 TI - Sleep disorders in childhood and adolescence. PMID- 2315236 TI - Sleep schedule-dependent causes of insomnia and sleepiness in middle childhood and adolescence. AB - Schedule-dependent sleep problems tend to increase as the youngster moves from middle childhood through preadolescence and into adolescence. This is partly because the youngster becomes more independent and parental control over both the selection of particular sleep schedules and the consistent maintenance of these schedules across weekends diminishes. Even accurate descriptions of the existing problem may become difficult to obtain. Nevertheless, specific syndromes are common and may be identified and treated. There may be increased demands at both ends of the sleep period leading to later bedtimes, earlier wakings, insufficient sleep, and daytime sleepiness. Periods of wakefulness confined to one portion of the night (beginning, middle, or end) may occur if sleep requirements are overestimated. Insomnia coupled with trouble waking may imply a circadian phase shift abnormality or a 'school-refusal' variant. And, variable sleep difficulties may be seen in a youngster with irregular schedules and poor sleep hygiene. Guidelines to the understanding, evaluation, and treatment of these syndromes are presented. PMID- 2315237 TI - Sleep disorders in childhood and adolescence. Introduction. PMID- 2315238 TI - Patterns of sleep and sleepiness in adolescents. AB - Most studies of adolescent sleep habits show a pattern of decreasing total sleep time, a tendency to delay the timing of sleep, and an increased level of daytime sleepiness. Laboratory tests have shown that adolescents do not have a decreased need for sleep but probably need more sleep than prepubertally. A number of factors affect the development of adolescent sleep patterns. Puberty itself imposes a burden of increased daytime sleepiness with no change in nocturnal sleep. Parental involvement in setting bedtimes wanes, though they become increasingly involved in waking teenagers in the mornings. Curfews and school schedules also affect adolescent sleep patterns, seen most commonly as imposing earlier rise times as the school day begins earlier during the adolescent years. Part-time employment has a significant impact on the sleep patterns of teenagers: those who work more than 20 h each week sleep less, go to bed later, are more sleepy, and drink more caffeine and alcohol. Development of circadian rhythms may also play a role in the phase delay teenagers commonly experience. The primary conclusion is that many adolescents do not get enough sleep. The consequences of the chronic pattern of insufficient sleep are daytime sleepiness, vulnerability to catastrophic accidents, mood and behavior problems, increased vulnerability to drugs and alcohol, and development of major disorders of the sleep/wake cycle. Educational programs hold the promise of improving teenagers' sleep patterns through informing youngsters, parents, and pediatricians about proper sleep hygiene and the risks of poor sleep habits. PMID- 2315239 TI - Heparin-induced hyperkalemia. AB - Heparin sodium is an extremely useful medication with demonstrated benefit in a number of clinical settings. Physicians need to be aware of the potential complication of hyperkalemia, especially in patients with renal insufficiency or diabetes mellitus. Discontinuation of heparin therapy is necessary to reverse the suppression of aldosterone. If heparin is the cause, the hyperkalemia will resolve within 5 days. PMID- 2315240 TI - Rocky Mountain spotted fever. When and why to consider the diagnosis. AB - Rocky Mountain spotted fever, caused by a rickettsial organism transmitted by the bite of a tick, can be confused with many more common diseases. Diagnosis is made more challenging by the fact that treatment is most efficacious if begun before the second week of illness. Tetracycline and doxycycline are the most successful therapeutic agents against this potentially fatal disease. PMID- 2315241 TI - Childhood obesity. AB - More effort should be invested in preventing obesity than is currently practiced, because prevention is much more successful than treatment, in either children or adults. Most obese children or adults. Most obese children have exogenous obesity, which is caused by increased caloric intake, reduced energy output, or overly efficient calorie utilization. These children are often tall for their age and have advanced bone age. Obesity in childhood is strongly associated with obesity in adulthood. The relationship between infantile obesity and obesity in childhood is less clear. Preventive measures in infants may include promotion of breastfeeding and delay in introduction of solid foods. Treatment in children includes abolition of junk foods and reduction in saturated fat in the diet and encouragement of regular physical exercise. PMID- 2315242 TI - Allergy testing by primary care physicians. AB - Primary care physicians will treat allergy to some degree purely because of supply and demand. The effectiveness of treatment depends on their interest and involvement. A thorough history and physical examination are essential. Physicians should not depend on a remote, computerized plan for diagnosis and treatment. Various diagnostic tests are available, some appropriate to nearly all levels of interest. Primary care physicians must choose between referral, pharmacotherapy, or more extensive involvement in allergy care. Immunotherapy involves some risk and a better possibility of pure result, but it requires additional training. Food allergy cannot be diagnosed by in vitro tests. Elimination and challenge with subsequent long-term elimination of offending foods is the only practical course for primary care physicians. PMID- 2315243 TI - Everyone needs a personal physician. PMID- 2315244 TI - Severe headaches. When to worry, what to do. AB - All patients who present with severe headaches merit careful medical and neurologic evaluation, and many require neuroimaging studies or lumbar puncture. To avoid missing the occasional seriously ill patient among the large number of patients with relatively benign headaches, physicians must maintain a high index of suspicion and a familiarity with the differential diagnosis. Patients with severe acute headaches must be evaluated for subarachnoid hemorrhage and bacterial meningitis. Temporal arteritis must be excluded in all older patients with recurrent headaches of recent onset. Trigeminal neuralgia and cluster headache usually do not signify serious underlying disease, but the severity of the pain mandates rapid diagnosis and institution of therapy. Migraines are extremely common and often mislabeled as tension or sinus headaches. All primary care physicians should be able to recognize the many faces of migraine and be familiar with symptomatic and prophylactic therapy. Difficult cases should be referred to a neurologist for ongoing care. PMID- 2315245 TI - Management of headaches. Focus on new strategies. AB - Migraine headaches can be successfully treated both abortively and prophylactically with carefully selected pharmaceutical agents. Mixed headache syndrome is complex and difficult to manage. Treatment is often complicated by patients' susceptibility to dependency and accompanying sleep disturbances, as well as by troublesome drug interactions. Cranial neuralgias can be successfully treated in the majority of cases. Since many patients with cranial neuralgias are elderly, careful monitoring of serum drug levels and frequent blood cell counts during therapy are crucial. PMID- 2315246 TI - How serious is the radon problem? AB - In the last year or two, a vast array of radon-detection kits has appeared in stores and catalogs. The authors explain what radon is and why it has captured the interest of the American public. They also examine the extent and significance of the radon problem and suggest solutions for homes that are found to have a high concentration. PMID- 2315247 TI - Treatment of asthma. New and time-tested strategies. AB - Early, aggressive therapy in conjunction with good communication with a knowledgeable, caring physician may reverse the trends of increasing morbidity and mortality from asthma. Allergen avoidance and immunotherapy are helpful in some patients. For those who need medication, bronchodilation with a beta 2 adrenergic drug, often in conjunction with an anticholinergic and theophylline, is the current treatment of choice for acute symptoms. For prophylaxis of chronic symptoms, sustained-release theophylline is still an excellent drug. However, an anti-inflammatory agent (eg, cromolyn sodium [Intal]) or, in some cases, an inhaled corticosteroid, may be an effective alternative. Whatever treatment is used, its success depends on effective self-management, which begins with education of the patient and family. PMID- 2315248 TI - Therapeutic drug monitoring. Practical considerations for primary care physicians. AB - Primary care physicians who understand the complexities of drug dosing may be able to provide their patients with more effective pharmacologic therapy. Standard or empirical methods of dosing are appropriate for most agents. The evolution of pharmacokinetics and clinically useful drug assays has led to pharmacokinetic dosing, a more sophisticated and exact method of dosing certain agents. PMID- 2315249 TI - When a depressed patient fails to improve. AB - In all depressed patients, an accurate and complete diagnosis of psychiatric as well as other medical conditions is essential. Diagnosis must be followed by adequate use of medications and an effective treatment plan that addresses all the relevant issues. In patients who have complex depressions and those who are unresponsive to adequate initial treatment with antidepressants, evaluation by a psychiatrist is recommended. A referral for psychotherapy, whether to a psychiatrist or other competent therapist, should follow appropriate diagnosis. PMID- 2315250 TI - Treatment of osteoporosis. What is the role of calcium? AB - On the basis of currently available information, the following recommendations can be made for treating osteoporosis. Women with no contraindications should maintain a total calcium intake of 1,000 mg daily before menopause and 1,500 mg daily after menopause. Calcium supplementation should be considered adjunct treatment in postmenopausal women and those who already have osteoporosis. At menopause, women with no contraindications should be given the option of taking estrogen to prevent osteoporosis. Vitamin D supplementation up to the recommended dietary allowance should be used in patients who may not get adequate dietary intake or sunlight exposure. Calcium carbonate should be the main calcium supplement when possible, because it is usually the least expensive and has the highest percentage of calcium. In older patients, who may have achlorhydria, calcium carbonate should be taken with food or another form of calcium that is well absorbed should be used. In compliant patients, calcium supplements should be given in two or three divided doses. Until more is known about exercise and osteoporosis, low-intensity exercise that promotes cardiovascular fitness should be prescribed. One appropriate regimen is brisk walking for 1 hour three times a week. PMID- 2315251 TI - Acute mediastinitis. What to do when the cause is nonsurgical. AB - Acute mediastinitis is a serious disease that requires prompt diagnosis and aggressive treatment. In each case, treatment should be individualized to the clinical presentation and suspected cause. The authors presented a general therapeutic scheme that may be used in the initial management of patients with acute mediastinitis from nonsurgical sources. PMID- 2315252 TI - The untold story. PMID- 2315253 TI - Deficiency of vitamins A, B, and C. Something to watch for. AB - Although specific vitamin deficiency syndromes are relatively rare in the United States, primary care physicians may encounter them in elderly patients and persons who consume minimal diets. Knowledge of such deficiencies is crucial in the evaluation of these patients. The authors discuss manifestations of deficiency of vitamins A, B, and C and recommend appropriate methods of diagnosis and treatment. PMID- 2315254 TI - Fibrocystic disease and breast cancer. PMID- 2315255 TI - Drug-induced illness in the elderly. PMID- 2315256 TI - Other causes of diarrhea. PMID- 2315257 TI - What are the facts on cholesterol? Questions physicians often ask about screening and treatment. AB - In spite of, or possibly because of, the many studies about cholesterol in the literature, some physicians remain confused or skeptical about the issues and conclusions. Reasonably clear evidence indicates that lowering the total serum cholesterol level can lessen the likelihood of primary coronary artery disease. There is no reason to believe that this benefit would not be conferred on women and the elderly, even though specific studies have not been done in these populations. Also, lowered cholesterol levels have been shown to correlate with regression of established atherosclerotic lesions. Moderate dietary changes can have significant impact on serum lipid levels in many patients, and a trial of low-dose drug therapy can usually identify those who may benefit from combination therapy. PMID- 2315258 TI - Acute gastrointestinal bleeding. A logical approach to management. AB - Management of acute gastrointestinal bleeding follows a logical sequence of steps. The first priority is to assess the magnitude of blood loss and resuscitate the patient. The patient history and nasogastric aspiration can help localize the source of bleeding to the upper tract or lower tract. Treatment of suspected upper gastrointestinal bleeding is usually empirical and consists of histamine 2 blockers (or sucralfate [Carafate]) or antacids. Diagnosis of the specific bleeding site is based on the severity, activity, and nature of the bleeding. Endoscopic and radiographic techniques may be useful. Intravenous vasopressin (Pitressin) therapy and endoscopic sclerotherapy are important in the management of variceal hemorrhage. Therapeutic endoscopic techniques are being used more often to manage nonvariceal bleeding as well. PMID- 2315259 TI - Endoscopic therapy for bleeding from the upper gastrointestinal tract. AB - Advances in endoscopic therapy have dramatically altered the approach to acute upper gastrointestinal tract hemorrhage. It can no longer be assumed that early endoscopic evaluation of this condition does not affect outcome. In the management of selected patients with nonvariceal hemorrhage, endoscopic therapy affects rates of rebleeding, need for surgery and transfusions, and length of hospitalization. For patients with variceal hemorrhage, the impact of endoscopic treatment is less clear. The endoscopic advances of the past decade have been exciting and have presented new challenges. Future investigators need to better define subgroups of patients who will benefit from this technology and determine which of the many techniques available will be safest and most efficacious. PMID- 2315260 TI - Decubitus ulcers. How to prevent them--and intervene should prevention fail. AB - Decubitus ulcers can develop in any chronically ill patient who is immobilized. Elderly patients and patients with spinal cord injury are at particularly high risk. Prevention is best achieved by identification of susceptible patients, alleviation of causative and predisposing factors, and early detection of ischemic skin changes. Treatment should be determined by the depth of tissue involvement. Conservative therapy is effective for shallow ulcers, whereas surgery, including the use of flaps, is reserved for deeper, more extensive lesions. PMID- 2315261 TI - Verapamil-induced inhibition of theophylline elimination in healthy humans. AB - The interaction between theophylline and verapamil was investigated in 7 healthy volunteers. Oral administration of verapamil in a dose of 120 mg t.i.d. for 7 days caused a significant inhibition of the elimination of theophylline (5 mg/kg intravenously). Theophylline clearance was reduced from 45.2 to 36.1 ml/hr/kg (20.1%; P less than 0.005). The apparent steady-state volume of distribution of the drug was not influenced. The terminal half-life of theophylline was increased from 6.80 to 8.23 hr (21.0%; P less than 0.001). Increased steady-state plasma theophylline concentrations may thus be expected when verapamil is added to a drug regimen which includes theophylline. PMID- 2315262 TI - Distribution of disulfiram and its chief metabolites over erythrocyte cell membranes and inactivation of erythrocyte aldehyde dehydrogenase activity. AB - The distribution of disulfiram (Antabuse over erythrocyte cell membranes and the inhibitory action of the parent drug and its metabolites on a disulfiram sensitive erythrocyte isozyme of aldehyde dehydrogenase (ALDH) was investigated in intact and haemolyzed human erythrocytes. These studies showed that not only disulfiram but also its bis(diethyldithiocarbamato) copper complex (Cu(DDC)2) were distributed over the erythrocyte cell membranes. In addition, disulfiram was the only substance examined that inactivaed erythrocyte ALDH, a reaction which was dependent on the concentration of disulfiram added. PMID- 2315263 TI - Inverse relationship between total glutathione S-transferase content and bile acid release in isolated hepatocytes from untreated, phenobarbital pretreated and hypothyroid rats. AB - The role of cytosolic anion binding proteins (glutathione S-transferases) in the hepatic transport of bile acids remains controversial. To investigate whether increased levels of the hepatocyte total glutathione S-transferase content were associated with changes in the release of bile acids from the hepatocyte, we measured the rate of release of radioactive bile acids in isolated hepatocytes from thyroidectomized, phenobarbital pretreated and untreated rats. The isolated hepatocytes were preincubated with either 14C-cholic acid or 14C-taurocholic acid, and the release rate of radiolabeled bile acids was determined. Hepatocyte total glutathione S-transferase content was measured by rocket immunoelectrophoresis. The release rate of the radiolabeled bile acids was significantly (P less than 0.005) decreased in both hypothyroid and phenobarbital pretreated hepatocytes. The levels of total glutathione S-transferase content were significantly (P less than 0.001) increased in the hepatocytes from both hypothyroid and phenobarbital pretreated animals. Our findings reveal a striking inverse relationship between the total glutathione S-transferase content of the hepatocyte and the release rate of radiolabeled bile acids in isolated hepatocytes from two independent animal models. These observations support the hypothesis that cytosolic anion binding proteins (glutathione S-transferases) may influence the net flux across the hepatocyte plasma membrane largely by limiting efflux. PMID- 2315264 TI - Influence of paracetamol and acetylsalicylic acid on the toxicokinetics of toluene. AB - To study the influence of paracetamol and acetylsalicylic acid on the toxicokinetics of toluene, 2 groups of 10 male volunteers were exposed to toluene vapor (3.25 mmol/m3, 4 hr) at two different exposure occasions: toluene alone and toluene + analgesics. Solvent concentrations in blood and hippuric acid concentrations in urine were measured during the exposure period and 3 hr after exposure. The concentration of toluene in blood increased after ingestion of paracetamol or acetylsalicylic acid, as compared to the control exposure. The ingestion of paracetamol significantly increased the area under the blood concentration versus time curve (P less than 0.05) and the apparent blood clearance was significantly reduced (P less than 0.05) after ingestion of paracetamol but not after ingestion of acetylsalicylic acid. No statistically significant differences in the urinary excretion of hippuric acid were found. PMID- 2315265 TI - Effects of lithium and rolipram enantiomers on locomotor activity in inbred mice. AB - Rolipram is a racemic drug that increases brain cAMP availability by inhibiting phosphodiesterase. Lithium, on the other hand, reduces cAMP levels in brain by inhibiting adenylate cyclase and by increasing phosphodiesterase activity. Inbred strains of mice were used in the present study to determine whether the opposite effects of lithium and rolipram on cAMP levels were evident from behavioural effects of the drugs. In the first experiment, locomotor activity was measured in strains of male and female mice given an injection of either vehicle, (+)- or (-) rolipram in order to find appropriate test conditions for studying interactions with lithium. (-)-Rolipram was more potent than its antipode in inducing hypokinesia, and the effects of (+)- and (-)-rolipram depended on mouse strain. In the second experiment, mice received lithium in their food for 3-4 weeks prior to testing, and they were then given an injection of vehicle, (+)- or (-) rolipram before behaviour tests. Lithium reduced locomotor activity in mice given the vehicle, whereas it counteracted activity-suppressant effects of rolipram. The behavioural findings are consistent with the opposite pharmacological effects of lithium and rolipram on cAMP, and support the notion that cAMP availability in brain may play a role in behavioural effects of lithium and rolipram. PMID- 2315266 TI - Effect of NO2 on lipids and lipid peroxidation in the CNS of the guinea-pig. AB - This study was undertaken to investigate the effect of nitrogen dioxide on some neurochemical parameters. Guinea-pigs were exposed to NO2, 5 p.p.m. and 10 p.p.m. for 2 hr daily for five weeks. The results showed significant depletion of the total lipids and phospholipids content of the cerebral hemisphere, cerebellum, midbrain and spinal cord following nitrogen dioxide intoxication. The results further revealed significant diminution in the cholesterol content of the NO2 intoxicated animals in cerebral hemisphere, cerebellum and midbrain. But on the other hand the level was significantly enhanced in the spinal cord. Interestingly, the rate of lipid peroxidation was found enhanced in all the investigated brain areas, and with increasing dosage the effect was correspondingly pronounced. PMID- 2315267 TI - Cocaine-induced arrhythmia in human foetal myocardium in vitro: possible mechanism for foetal death in utero. AB - We examined the acute in vitro effects of cocaine on cell membrane potentials and contractility of 12-16 week old human foetal heart, to better assess the potential for the induction of serious arrhythmia, in utero, by this abused substance. Ventricular preparations were maintained in a tissue bath, and continuously provided with oxygen and glucose during the measurement of membrane potentials with microelectrodes, and developed force of contractions with microforce transducers. Cocaine (600 ng/ml) had a significant effect on the ability of the heart to produce action potentials of normal rising velocity, amplitude, and duration. Within 90 min., all electromechanical activity had ceased. Under the conditions of our study, the effects of cocaine were reversible, however, reversibility in vitro may have no counterpart in utero, and irreversible loss of cardiac function may result. PMID- 2315268 TI - Pharmacokinetics of recombinant human erythropoietin in chronic haemodialysis patients. AB - Single dose intravenous and subcutaneous pharmacokinetics of recombinant human erythropoietin (rhEPO) has been determined in 6 chronic haemodialysis patients. Four patients, all on maintenance therapy with rhEPO, were consecutively treated both intravenously and subcutaneously with injections of rhEPO in a dose of 50 U/kg. Two previously untreated patients received 150 U/kg of rhEPO intravenously and subcutaneously. After intravenous injection of 50 U/kg of rhEPO a mean serum half-life value of 5.4 +/- 0.9 hr was found. The corresponding half-life after injection of 150 U/kg was 7.6 hr. The peak concentration of serum EPO after subcutaneous injection was 12.5-20 times lower than the corresponding intravenous Cmax. After administration of 150 U/kg subcutaneously the absorption of EPO was monitored to completion at 120 hr. The complete bioavailability of subcutaneous rhEPO after injection of 150 U/kg was 31.7%. Whether this low and protracted subcutaneous absorption of rhEPO is accounted for by either impeded absorption or partial skin degradation of rhEPO is not known. PMID- 2315269 TI - Accumulation and turnover of metabolites of toluene and xylene in nasal mucosa and olfactory bulb in the mouse. AB - Autoradiography of male mice following inhalation of the radioactively labelled solvents, toluene, xylene, and styrene, revealed an accumulation of non-volatile metabolites in the nasal mucosa and olfactory bulb of the brain. Since no accumulation occurred after benzene inhalation, it was assumed that the activity represented aromatic acids, which are known metabolites of these solvents. This was supported by the finding that also radioactive benzoic acid (main metabolite of toluene) and salicylic acid accumulated in the olfactory bulb. High performance liquid chromatography revealed that after toluene inhalation (for 1 hr), nasal mucosa and olfactory bulb contained mainly benzoic acid, with a strong accumulation in relation to blood plasma, and considerably less of its glycine conjugate, hippuric acid. After xylene inhalation, on the other hand, methyl hippuric acid dominated over the non-conjugated metabolite, toluic acid. The results indicate a specific, possibly axonal flow-mediated transport of aromatic acids from the nasal mucosa to the olfactory lobe of the brain. The toxicological significance of these results remains to be studied. PMID- 2315270 TI - Tissue distribution, metabolism, and excretion of 14C-TCDD in a TCDD-susceptible and a TCDD-resistant rat strain. AB - A comparative study was carried out in the most TCDD-resistant [Han/Wistar (H/W), LD50 greater than 3000 micrograms/kg] and the most TCDD-susceptible [Long-Evans (L-E), LD50 about 10 micrograms/kg] rat strain to assess the significance of kinetic factors in TCDD toxicity. Young adult males of both strains were administered 5 micrograms/kg (1.9 microCi/kg) 14C-TCDD intraperitoneally. Four rats per strain were killed at 4 hr, 1, 4, 8, 16, and 32 days after exposure. A total of 22 tissues along with blood and serum were sampled for liquid scintillation counting. From half of the animals, daily urine and faeces were also analyzed. In addition, 3 rats per strain were given 50 micrograms/kg (19 microCi/kg) 14C-TCDD and prepared for whole-body autoradiography after 1, 4 or 8 days. The livers of two rats per strain killed at 4 hr, 4 or 16 days, and the excreta from two rats of both strains collected on days 1-4, 5-8, 13-16, and 29 32 after exposure were analyzed for metabolites of TCDD by high pressure liquid chromatography. The label was mainly excreted in faeces as metabolites of TCDD, and the half-life of elimination was 20.8 (L-E) or 21.9 (H/W) days. A very similar overall distribution pattern was observed in both strains irrespective of dose, and the liver was the major site of accumulation. Practically all liver 14C activity was found as the parent compound. Moderate strain-related differences were observed in the thyroid, thymus, prostate, adrenals, and brown and white fat, where lower values were recorded in H/W rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2315271 TI - Neurochemical correlates of affective disorders and their treatment. A satellite symposium affiliated to the XVIth C.I.N.P. Congress. August 21-24, 1988. PMID- 2315272 TI - [Theraplay--a direct communication play therapy]. AB - This paper introduces the basic concepts and the application of the directive short-term play therapy called Theraplay. Goals and methods are illustrated by examples from the assessment (Marschak Interaction Method) and by sessions with a 6 year old regressive noncompliant mutistic twin. PMID- 2315273 TI - [School phobic behavior--etiologic conditions and follow-up]. AB - The histories, results as well as treatment and courses of 38 children and juveniles (25 boys, 13 girls) with schoolphobic behaviour were exposed and analysed with regard to there aetiological and improvement circumstances. In 34 pupils (63%) schoolphobic behaviour was an expression of a depressive state demanding appropriate treatment, usually antidepressant drugs. In those 14 pupils (10 boys, 4 girls) who did not suffer from a depressive state the following subgroups were established: 1 Pupil with decisive school problems (lack of achievements, problems in relating towards schoolmates). 2 Pupils with a decisive conflict (ambivalence between dependence and independence). In these pupils schoolphobic behaviour was preceded by a change of there school or form respectively their schoolmates. 3 Pupils with decisive psychosocial interactions. As a distinguished constellation which might be another factor in the aetiology of schoolphobic behaviour the reactivation of oedipal conflicts was exposed. This applies to pupils with and without depressive states. In all pupils with repeated schoolphobic behaviour depressive states were diagnosed. Whenever the onset of schoolphobic behaviour led to a change of school form prolonged avoiding of the school was the result. PMID- 2315274 TI - Prenatal analysis of insulin receptor autophosphorylation in a family with leprechaunism. AB - We describe a method for the isolation and functional characterization of insulin receptors from chorionic villi and cultured amniotic fluid cells. The functionality of these receptors is assayed by measuring the insulin-induced stimulation of autophosphorylation of the receptor beta-chain. The method is expected to allow the prenatal diagnosis of those forms of leprechaunism and related diseases which are the result of a decreased stimulation by insulin of receptor autophosphorylation. A pregnancy at risk for leprechaunism was examined and an unaffected child was correctly predicted by study of the functionality of the insulin receptor on cultured amniocytes and by echoscopic examination. PMID- 2315275 TI - Fetal blood sampling demonstrating chimerism in monozygotic twins discordant for sex and tissue karyotype (46,XY and 45,X) AB - Fetal blood sampling has been used in the genetic work-up of twin gestations for rapid karyotyping. We present a case of twins which on ultrasound evaluation revealed hydrops fetalis in one twin and a normal second twin. Fetal blood sampling revealed the presence of mosaicism for 46,XY/45,X in both twins. HLA antigen testing showed the twins to be identical. The patient elected pregnancy termination. Blood chromosomal analysis after delivery revealed both twins to have 46,XY/45,X mosaicism, but the twin with signs of hydrops fetalis had tissue chromosomes of 45,X and the normal twin had tissue chromosomes of 46,XY. Amniotic fluid chromosomal analysis revealed 46,XY in twin A and 45,X in twin B. This represents a case of identical (monozygotic) twins with sex discordance. In this case, there was the probable occurrence of post-zygotic chromosomal non disjunction leading to the discordancy of the sex in this set of twins. With the presence of vascular communication in monozygotic twins, there is the possibility of exchange of blood in monozygotic twins and the result of blood chimerism in twins. PMID- 2315276 TI - Exclusion of chromosomal mosaicism in amniotic fluid cultures: efficacy of in situ versus flask techniques. AB - Accurate diagnosis of mosaicism in amniotic fluid cell cultures represents a major problem. If insufficient cells are analysed, true fetal mosaicism may go undetected. False-positive diagnosis is also possible since a second cell line may arise in vitro and not reflect the true fetal genetic constitution. These difficulties apply to both flask and in situ culture techniques, to varying degrees. The relative accuracy of flask versus in situ culture techniques in excluding mosaicism was determined by statistical analysis of experimental data from ten pairs of mixed male-female amniotic fluid specimens. The data support the idea that the majority of in situ colonies are independent of one another. The following conclusions are drawn: (1) analysis of a single metaphase from a number of different colonies enhances the confidence for excluding mosaicism; (2) analysis of more than one cell per colony offers little advantage; (3) exclusion of a given level of mosaicism requires analysis of fewer metaphases using the in situ method; (4) the confidence for excluding mosaicism is high with both in situ and flask techniques, using the provided guidelines; and (5) it is shown that the two-stage approach used by many laboratories is currently the most efficient way to exclude mosaicism. PMID- 2315277 TI - [Asbestos types, lung dust analysis, exposure and latency time of malignant mesotheliomas in German Switzerland]. PMID- 2315278 TI - [The etiopathogenesis of infantile coronary sclerosis in so-called Kawasaki syndrome]. PMID- 2315279 TI - [Progress in pathology?]. PMID- 2315280 TI - Sexual cycle of Babesia divergens confirmed by DNA measurements. AB - The DNA content of the developmental stages within the life cycle of Babesia divergens was measured by means of fluorescence microscopy using the DNA-specific bisbenzimide Hoechst 33258. By comparing the mean relative fluorescence intensities, the assumption of sexual reproduction in the gut of the tick vector (Ixodes ricinus) was confirmed. However, no proof of a pre- or postzygotic meiosis was found. PMID- 2315281 TI - Light and electron microscopic studies on Myxobolus cotti el-Matbouli and Hoffmann, 1987 infecting the central nervous system of the bullhead (Cottus gobio). AB - Myxobolus cotti (Myxozoa: Myxosporea) is described as found in the central nervous system of the bullhead (Cottus gobio) caught in the Alpine lake Konigssee and in a brook in the Bavarian Forest, Federal Republic of Germany (El-Matbouli and Hoffmann 1987). Aggregations of spores and polysporoblastic trophozoites compressed and replaced large areas of the white and grey matter of the brain and spinal cord. These aggregations may be surrounded by a thin, connective tissue capsule; in a few cases they were associated with loose infiltrates of glial cells. Neither conspicuous tissue reactions nor inflammatory responses were evident. No other organs were seen to be infected with M. cotti. Mature spores are oval, with a tapering anterior end, and the pyriform polar capsules are nearly equal in size. Fresh spores measured 8.9-15.1 microns in length (mean, 12.4 microns) and 8-12.4 microns in width (mean, 9.6 microns); polar capsules were 4.3-9 microns long (mean, 6.4 microns) and 2-3.8 microns wide (mean, 2.9 microns). Light microscopy, the ultrastructure of pansporoblasts, sporogenesis and mature spores are described. PMID- 2315282 TI - Light and electron microscopic observations on the swimbladder stages of Sphaerospora renicola, a parasite of carp (Cyprinus carpio). AB - The developmental cycle of stages of Sphaerospora renicola, proliferating in the walls of the swimbladder in carp fry and responsible for swimbladder inflammation (= SBI stages) is described. The initial stage, a primary cell containing two secondary cells, grows in size while the secondary cells divide and produce two tertiary cells each by endogenous division. After a supposed disintegration of the grown primary cell, the cell triplets are released to repeat the cycle. The cell divisions are asynchronous and the development of the whole formation may be quite irregular. The cytology of these stages is closely reminiscent of the blood stages of S. renicola and also shares common features with the parasite's sporogonic stages. The SBI stages show typical features of myxosporean organisation, i.e., a "cell-within-cell" arrangement in which the primary cell contains secondary cell(s) in membrane-bound vacuoles and many free ribosomes, in the absence of centrioles. Other salient features of SBI stages are partitions in the nuclei; a small amount of cytoplasm in the early secondary cells; distinct, age-dependent changes in morphology of the nucleus; and atypically shaped Golgi bodies in the cytoplasm or integrated with the nuclear envelope. The cytological features and significance of swimbladder stages are discussed in detail. PMID- 2315283 TI - Chemotherapy of experimental Echinococcus multilocularis in jirds. AB - A total of 50 jirds (Meriones unguiculatus) were infected by intraperitoneal implantation of 0.20 g metacestode tissue of Echinococcus multilocularis. The feed of 4 groups of 10 animals each was treated for 35 days with 500 ppm albendazole, flubendazole, mebendazole or praziquantel; 1 group of 10 jirds served as unmedicated controls. At autopsy 2 weeks after the end of medication, the transplants had increased in size and weight, reaching a total weight of 78.11 g in the control group, 21.60 g in the albendazole-treated group, 3.63 g in the flubendazole-treated group, 7.00 g in the mebendazole-treated group and 68.91 g in the praziquantel-treated group. The percentage in reduction of parasitic tissue weight as compared with control values was 72%, 95%, 91% and 12%, respectively. The calculated daily drug intake was approximately 48 mg/kg body weight. Drug-related side effects were not observed. PMID- 2315285 TI - The fine structure of the embryonic envelopes before and after hatching in bothriocephalids: physiological and ecological significance. AB - The fine structure and differentiation of the embryonic envelopes before and after hatching in two bothriocephalid species of teleostean fish are described. Scanning electron microscopic observation of the egg surface confirmed the specific ornamentation of the capsule. Its thickness and topographic morphology reflect the physiocochemical characteristics of the environment. Beneath the eggshell, two syncytial layers were observed around the oncosphere. The outer envelope, visible during the preoncospheral phase, degenerated before the liberation of the coracidium. Glycoconjugate labelling confirmed the nutritive character of this layer. After hatching, the inner envelope was the only layer covering the oncosphere. The apical plasma membrane of the coracidial sheath bore cilia and numerous clublike microvilli. Beneath the cortical zone, the syncytial cytoplasm was vacuolated, resembling a honeycomb; the electron-dense zone, described from other pseudophyllideans, was not present. The basal membrane of the inner envelope, uniformly electron-dense, was assimilated by the oncospheral membrane. Comparison of the composition of the embryonic envelopes of pseudophyllideans with those of other tapeworm orders and trematodes revealed ontogenetic, structural and functional similarities between the embryotrophic layers. The physiological and ecological significance of the structure of the free-swimming coracidium is discussed. In this respect, the inner envelope around the oncosphere appears to be responsible for the inability of the larva to detect and invade the intermediate host. PMID- 2315284 TI - The effect of the hydrogen ionophore closantel upon the pharmacology and ultrastructure of the adult liver fluke Fasciola hepatica. AB - The present study describes the effects of the H+ ionophore and anthelmintic closantel upon the in vitro motility and in vivo ultrastructure of the liver fluke, Fasciola hepatica. At a concentration of 50 micrograms/ml, closantel caused an initial stimulation, then suppression of activity, which was accompanied by an increase in muscle tone and led to a spastic paralysis within 2 h. The pattern of response was similar at lower concentrations, although the initial stimulation was not always evident, but the onset of paralysis could be reached more quickly. Scanning electron microscopy revealed gross surface damage from 24 h onwards in vivo, in the form of erosion of the anterior and posterior extremities of the fluke and large-scale sloughing of the tegument on both dorsal and ventral surfaces. Tegumental changes prior to sloughing included some swelling of the basal infolds and an apical accumulation of T1 secretory bodies. In the underlying tegumental cells there was reduced secretory activity and the mitochondria were consistently swollen and deformed. Reduced secretory activity was a feature of the gastrodermal cells as well; these cells were characterized by swollen, electron-lucent mitochondria, vesiculated GER cisternae and apical blebbing of packets of cytoplasm. The vitelline follicles became severely disrupted as a result of the breakdown of the nurse cell cytoplasm. The stem and intermediate type 1 (It1) cells rounded up and showed nuclear abnormalities. There did not appear to be a severe disruption of shell protein production in the intermediate vitelline cells, but there was a noticeable absence of glycogen in the mature vitelline cells. The effects of closantel are discussed in relation to its proposed mode of action as an uncoupler of oxidative phosphorylation. PMID- 2315286 TI - Praziquantel treatment of porcine brain and muscle Taenia solium cysticercosis. 1. Radiological, physiological and histopathological studies. AB - Porcine Taenia solium cysticercosis, recognized as a model of the human disease, was used to analyze the effect of the anthelminthic drug praziquantel on hosts and parasites. The drug (50 mg/kg daily) was given over 15 days in the feed of 13 cysticercotic and 9 control pigs. Changes in the number, size and appearance of brain parasites were seen by computerized tomography immediately after the last dose of praziquantel, although not all cysticerci had disappeared by day 47 following the end of the treatment. Muscle parasites became small and hyperdense shortly after treatment and disappeared from tomographic images afterwards. No alterations were found in EEGs or in brain-stem auditory and somatosensory evoked potentials. Muscle cysticerci showed increasing degrees of degeneration with time after treatment, and an augmented inflammatory reaction was concomitantly observed. In contrast, more heterogeneous results were obtained in parasites lodged in the brain, since viable cysts and less intense inflammatory reactions were found in the brain at different times after treatment. Physiological evaluation of the parasites showed that evagination was inhibited immediately after treatment and that oxygen consumption decreased with time. The results of this investigation suggest that praziquantel damages cysticerci and that the inflammatory reaction destroys and eliminates them. PMID- 2315287 TI - Visceral pathology and size of the host snail: comparative studies in Lymnaea glabra infected by Fasciola hepatica. PMID- 2315288 TI - Polyamine concentrations in pancreatic tissue, serum, and urine of patients with pancreatic cancer. AB - We investigated the total, free, and acetylated polyamine concentrations in pancreatic tissue, serum, and urine of 20 patients with pancreatic cancer, 30 healthy volunteers, and 40 patients with nonmalignant, gastrointestinal diseases by reversed-phase liquid chromatography. Tissue concentrations in carcinoma compared to histologically unaffected pancreas were significantly higher for putrescine, elevated for cadaverine, and nearly identical for spermidine and spermine, while N1-acetylspermidine was detectable in cancer tissue only. With the exception of free spermine in urine and total spermine in serum, all other polyamines were significantly elevated in the urine and serum of cancer patients compared to healthy controls. These data support the concept that polyamines play an important role in rapidly growing tissues. However, nonmalignant gastrointestinal diseases partly showed similar elevations. Because of this low specificity, polyamines are of little value only as diagnostic markers of pancreatic carcinoma. Since polyamine concentrations normalized in patients after curative operation while they were further elevated in patients with tumor relapse or metastases, polyamines might play a clinical role in predicting therapeutic success or indicating relapse of the tumor. A significant linear correlation of polyamine concentrations and the size of the tumor was found while a significant correlation to CEA, CA 19-9, and CA 125 or the presence of organ metastases did not exist. PMID- 2315289 TI - Effect of ursodeoxycholic acid (UDCA) on pancreatic enzyme secretion and gallbladder emptying. AB - We have used a duodenal perfusion technique to study the effect of chronic administration of ursodeoxycholic acid (UDCA) on postprandial pancreatic enzyme secretion and gallbladder emptying. Duodenal output and hepatic secretion rate of bile acid were also measured. Six gallstone subjects were studied during an evening meal and an overnight fast before and during UDCA administration (675 mg/day for 6 weeks). During the first postprandial hour, the duodenal trypsin output was reduced from 253 to 164 IU/kg/h (p less than 0.05), and mean gallbladder ejection fraction from 38 to 20% (p less than 0.05). The peak response to the meal was delayed from 30 to 50 min for trypsin output (NS) and from 25 to 45 min for gallbladder ejection fraction (p less than 0.05). Area under the curve during the first postprandial hour was decreased for trypsin output from 225 to 119 IU/kg (p less than 0.025), and for gallbladder ejection fraction from 43 to 19% (NS); but areas for the second postprandial hour were increased, so that total values were unchanged. We conclude that the pattern of response for both end organs during chronic UDCA is better described as an attenuated response to food, rather than as a simple reduction in response; and that, since the effects were unaccompanied by any quantitative changes in hepatic bile acid secretion rate, they were probably mediated via the qualitative change in biliary bile acid composition known to accompany chronic UDCA administration. PMID- 2315290 TI - Altered synthesis of some secretory proteins in pancreatic lobules isolated from streptozotocin-induced diabetic rats. AB - The in vitro incorporation of [35S]cysteine into lipase, colipase, amylase, procarboxypeptidase A and B, and the serine proteases and total proteins was studied in pancreatic lobules isolated from normal and diabetic rats with or without insulin treatment. The incorporation of [35S]cysteine into total proteins was 65% greater in pancreatic lobules from diabetic animals than from normal rats. The increased incorporation was partly reversed by insulin treatment (2 U/100 g/day for 5 days) of diabetic rats. The relative rates of biosynthesis for amylase and the procarboxypeptidases in diabetic pancreatic lobules were decreased by 75 and 25%, respectively, after 1 h of incubation, while those for lipase, colipase, and the serine proteases were increased by 90, 85, and 35%, respectively. The absolute rates of synthesis for these enzymes changed in the same direction as the relative rates in diabetic lobules, except that for the procarboxypeptidases, which did not change. The changed rates of biosynthesis for the pancreatic enzymes were reversed by insulin treatment of the diabetic rats. Kinetic studies showed that the incorporation of [35S]cysteine into amylase, lipase, and colipase was linear until up to 2 h of incubation in normal pancreatic lobules, while in the diabetic lobules the incorporation into lipase and colipase was accelerated, reaching a plateau level already after 1 h of incubation. It is concluded that the biosynthesis of pancreatic secretory proteins in diabetic rats is greatly changed both in terms of quantity and kinetics. PMID- 2315291 TI - Decreased levels of serum alpha-isoamylase prior to diabetes onset in BB rats. AB - The development of insulin-dependent diabetes mellitus (IDDM) includes a prodrome of autoimmunity against pancreatic beta cells. The period of subclinical islet cell disease with altered beta-cell function may be prolonged. We have determined the serum pancreatic alpha-isoamylase in both young diabetes-prone (DP) and newly diabetic BB rats to test whether changes in the pancreas prior to IDDM are reflected by this enzyme, shown to be regulated by insulin. A prospective analysis of inbred BB rats (n = 28) that later developed diabetes showed that the alpha-isoamylase at the time of onset was reduced by 19% (p less than 0.02) compared with levels observed 1 week earlier and by 30% (p less than 0.01) compared with levels 2 weeks before onset. Furthermore, when compared to age matched diabetes-resistant (DR) BB rats in a cross-sectional study, the DP BB rats investigated in groups at 20, 30, 40, 50, 60, and 70 days of age had significantly lower (p less than 0.01) serum alpha-isoamylase already from 50 days of age, which is 2-6 weeks prior to the expected onset of diabetes. Finally, in 70-day-old cofostered DP and DR male rats with identical body weight and rates of growth, the serum alpha-isoamylase was decreased in the DP yet nondiabetic (n = 8) rats compared with the DR (n = 8) rats (p less than 0.05). Reduced levels of serum alpha-isoamylase, therefore, may reflect loss of beta cells or beta-cell function in the pancreas of diabetes-prone but not yet diabetic BB rats. PMID- 2315292 TI - Acinar cholecystokinin (CCK) receptors in the exocrine pancreas of the rat: effect of adrenalectomy. AB - The binding of [125I]BH-CCK-8 to membranes of acinar cells from rats at 6 and 21 days after adrenalectomy was studied. The optimum conditions of time and temperature were previously established as being 120 min and 30 degrees C. Under these conditions, the membranes of the adrenalectomized animals of both groups (6 and 21 days) bound more radioligand than those from control rats. However, a qualitative study of the binding showed that the affinities of binding were much lower; in particular, the high affinity receptors had a Kd of 0.94 +/- 0.33 nM in the controls and this was 14.9 +/- 1.29 nM in the 6-day adrenalectomized animals, although the maximum binding capacity did not vary significantly. However, in the case of the low affinity receptors, there was a gradual increase in the maximum binding capacity as the time after adrenalectomy progressed: 717 +/- 121, 1,987 +/- 183, and 10,175 +/- 862 fmol/mg for the control, 6-day, and 21-day adrenalectomized rats, respectively. In the latter situation, the high affinity receptors completely disappeared. These results, which coincide with a marked deficit in protein secretion already described in adrenalectomized rats, can be accounted for in terms of the possible negative cooperativity exerted by the low affinity receptors on the high affinity hormone-receptor complex, the protein secretion of the acinar cells normally mediated by the high affinity receptors becoming paralyzed. PMID- 2315293 TI - Increased canine pancreatic acinar cell damage after organophosphate and acetylcholine or cholecystokinin. AB - Sublethal doses of organophosphate anticholinesterases cause acute pancreatitis in dogs within 2 h. In vitro studies using canine pancreatic fragments have also demonstrated that the peak of amylase release in response to acetylcholine is shifted far to the left after incubation with the organophosphates echothiophate (10(-4) M) or tetraisopropyl pyrophosphoramide (iso-OMPA) (10(-3) M), indicating an increased sensitivity of response. The present in vitro study examined whether there was also an increased susceptibility to acinar cell damage at the electron microscopic level after acetylcholine or cholecystokinin. Minced pieces of whole fresh canine pancreas 2-3 mm in size were placed in buffered Eagle's solution and gassed with 100% O2. After pretreatment 1 h with echothiophate or iso-OMPA, they were then incubated with acetylcholine (10(-5) M). Other tissues preincubated with echothiophate were stimulated with cholecystokinin (10(-9) M). These are submaximal doses for untreated canine pancreatic fragments. After acetylcholine and echothiophate or acetylcholine and iso-OMPA, there was extensive acinar damage with the appearance of large vacuoles and lakes, and interstitial edema. There was evidence of intense supramaximal stimulation and lateral exocytosis. Similar destructive changes were seen after echothiophate and cholecystokinin. In control sections from tissues stimulated with acetylcholine (10(-5) M) or cholecystokinin (10(-9) M, there were lumenal exocytotic patterns typical of submaximal stimulation. Other controls, organophosphate alone and unstimulated basal conditions, showed only minor changes. It is concluded that the increased sensitivity to acetylcholine after organophosphate incubation correlates with an increased susceptibility to acinar ultrastructural damage from acetylcholine and cholecystokinin. PMID- 2315294 TI - Intestinal phase of pancreatic polypeptide release: the effect of segmental perfusion of the small intestine with various secretagogues. AB - The purpose of this study was to examine the effect of various nutrients perfused selectively into isolated sections of the small intestine on the release of pancreatic polypeptide (PP). Six dogs were prepared with chronic gastric, duodenal, and three permanent intestinal fistulas (one distal to the ligament of Treitz, one in the terminal ileum, and one halfway between). After a 24-h fast, the duodenum was perfused for 45 min (200 ml/h) via the duodenal limb with HCl (30 mM), an amino acid solution (50 mM), or sodium oleate (NaO, 40 mM). In separate studies, the jejunal and ileal segments were isolated by inflating two balloon catheters via the intestinal fistula, and these segments were perfused as described earlier. Plasma PP, cholecystokinin (CCK)-33, and secretin levels were measured. Results of this study showed that the perfusion of all segments of the small intestine with amino acid caused a significant elevation of plasma PP levels. Perfusion of the duodenum and jejunum but not the ileum with a fatty acid resulted in a significant elevation of plasma levels of PP. Perfusion of HCl into any segment did not affect plasma levels of PP. This study shows that PP is released by the presence of nutrients in all segments of the small intestine, and that a PP elevation was always accompanied with a rise in plasma levels of CCK 33. PMID- 2315295 TI - Injection of microspheres into pancreatic arteries causes acute hemorrhagic pancreatitis in the rat: a new animal model. AB - Alterations in the vascular bed of the pancreas or disturbances of the blood coagulation system are mostly considered to be sequelae of acute pancreatitis, but it seems that impairment of the pancreatic blood supply can per se lead to acute hemorrhagic pancreatitis. To test this hypothesis with a new animal model, we injected 20 microns polystyrene microspheres retrogradely into the distal splenic artery of rats, thus incompletely blocking blood perfusion in the splenic portion of the pancreas. Eight of eight rats (100%) subjected to microsphere injection developed acute hemorrhagic pancreatitis by 27 h after surgery, when they were killed, but none of the six sham-operated control animals (0%) showed macroscopic signs of pancreatitis. Blood amylase levels at death were 3,087 +/- 650 I.U./L (mean +/- SEM) and the histologic severity score for pancreatitis was 10.8 +/- 1.0 (mean +/- SEM), whereas in the six control rats amylase levels were 1,375 +/- 158 I.U./L and the histology score was only 1.7 +/- 1.0. The result is, with p less than 0.0005, highly significant (chi 2 analysis) and shows that acute experimental pancreatitis can indeed be induced by partially blocking the arterial blood supply within the organ. PMID- 2315296 TI - Role of cholecystokinin in bombesin-stimulated pancreatic enzyme secretion in conscious rats. AB - Since bombesin is a potent stimulus of cholecystokinin (CCK) secretion, it is assumed that the stimulatory effect of bombesin on pancreatic protein secretion is mediated by CCK. This study was undertaken to determine in the conscious rat with a cannulated pancreatic duct the role of CCK in the stimulation of pancreatic protein secretion by bombesin. Infusion of 18 pmol/kg/30 min of bombesin into rats stimulated pancreatic protein secretion from 6.7 +/- 1.1 to 9.9 +/- 0.4 mg/30 min (p less than 0.05). This stimulation of pancreatic protein secretion was accompanied by a significant increase in plasma CCK, measured by a specific and sensitive radioimmunoassay, from 3.2 +/- 0.2 to 4.7 +/- 0.2 pM (p less than 0.01). When a similar plasma CCK increment as during infusion of bombesin (1.5 +/- 0.2 pM) was achieved by infusion of 6 pmol/kg/30 min of exogenous CCK (1.6 +/- 0.3 pM), pancreatic protein secretion increased only from 6.9 +/- 0.7 to 7.6 +/- 0.7 mg/30 min (p less than 0.05). To achieve a pancreatic protein secretion similar to that during bombesin, large doses of exogenous CCK (24 pmol/kg/30 min) were needed, resulting in considerably higher plasma CCK concentrations of 10.9 +/- 0.7 pM. It is concluded that CCK is unlikely to play a significant role in the stimulation of pancreatic protein secretion by bombesin in the rat. PMID- 2315297 TI - Structural and functional effects of long-term alcohol administration on the dog exocrine pancreas submitted to two different diets. AB - Our purpose was to study the influence of two different levels of dietary protein and fat on the action of chronic alcohol feeding on the exocrine pancreatic secretion and the pancreatic morphology of conscious dogs. Ten animals were provided with gastric and duodenal cannulas. Five of them (group H) received a high-protein (39% of calories), high-fat (34%) diet, and the five others (group L) a moderately low-protein (15%), low-fat (20%) diet. Animals were housed in closed kennels lightened with artificial light and did not have free access to sunlight. Five series of experiments were performed just before and 5 and 12 months after daily alcohol administration through the gastric cannula (2 g/kg/day). Volume, bicarbonate, and protein were measured under basal conditions after intragastric ethanol infusion (1.5 g/kg), under hormonal stimulation with 1 clinical unit (CU)/kg/h secretin or 1 CU/kg/h secretin plus 3 Crick Harper Rate (CHR) U/kg/h cholecystokinin (CCK), before and after intravenous ethanol 1.3 g/kg for 20 min, and after intragastric ethanol (1 g/kg) given with a meal. Group H was the most sensitive to the action of chronic alcohol feeding. At the end of 1 year of alcohol administration, volume and bicarbonate were not affected, but protein secretion was significantly increased in basal conditions and under secretin infusion, but not under CCK infusion or in response to a meal. The secretory pattern of these dogs was different from the response of dogs studied in previous experiments having the same diet but housed in an open kennel and having free access to outside and sunlight. In group L, protein was less affected, but volume and bicarbonate were significantly decreased 1 year under secretin stimulation. Histological damages were seen in the two groups characterized by a slight periacinar fibrosis and alterations of ductal cells. Acinar and ductal luminae were dilated and filled with protein plugs also present in pancreatic juice and able to stop the flow of juice. At the difference from human beings, these plugs were built up of all secretory protein but not of an insoluble fibrillar molecular form of pancreatic stone protein. This study confirms the role of chronic alcoholism on the formation of protein plugs and shows the influence of nutritional and environmental conditions. PMID- 2315299 TI - The following protein sequences were reprinted from the protein sequence database of the Protein Identification Resource (PIR). PMID- 2315298 TI - Hemerythrin from Lingula unguis consists of two different subunits, alpha and beta. AB - Hemerythrin, a non-heme Fe-protein, of Lingula unguis has an octamer structure. We demonstrated that the protein is composed of two distinct subunits (alpha and beta), in equal amounts by investigation of their composition and partial terminal sequence. The cross-linking reaction of the native protein with dithiobis-(succinimidyl propionate) provided evidence for the presence of a dimer composed of alpha and beta subunits. PMID- 2315300 TI - Estimation of protein secondary structure from circular dichroism spectra: a critical examination of the CONTIN program. AB - The computer program CONTIN uses the Provencher and Glockner procedure to calculate protein secondary structure from circular dichroism spectra. We have tested this program with peptides and proteins in which unfolding was either induced by denaturing treatment or was already present. Results indicate that the program does not clearly discriminate between the ordered and the unordered states of a protein. PMID- 2315301 TI - Expression and secretion of aequorin as a chimeric antibody by means of a mammalian expression vector. AB - A fusion protein has been expressed from the relevant genes in mammalian cells consisting of the photoprotein aequorin and an anti-4-hydroxy-3-nitrophenacetyl antibody gene. This chimeric antibody has allowed the development of a sensitive luminescent immunoassay. Initially the cDNA of the photoprotein aequorin from Aequorea victoria was cloned and expressed in Escherichia coli. The gene was expressed as apoaequorin and, by using luciferin isolated from Renilla reniformis, its activity was found essentially identical to native aequorin. The aequorin gene was subcloned into a mammalian expression vector to produce a fusion protein directing secretion of apoaequorin; the aequorin gene was fused to the 3' terminus of an immunoglobulin heavy-chain gene that directed expression of an anti-4-hydroxy-3-nitrophenacetyl antibody. The gene fusion contained the variable region, the constant region domain 1, and part of domain 2 for the IgG2b mouse immunoglobulin, followed by the aequorin gene. Transfection of the chimeric gene into a cell line expressing the complementary lambda 1 light chain, J558L, allowed recovery of a chimeric antibody with binding specificity for the 4 hydroxy-3-nitrophenacetyl group and the related 4-hydroxy-3-iodo-5 nitrophenacetyl hapten. The Ca2(+)-dependent bioluminescent activity of aequorin was also recovered. PMID- 2315302 TI - Average locus differences in mutability related to protein "class": a hypothesis. AB - Substantially less genetic variation has been recognized in studies of the proteins of nucleated cells by the technique of two-dimensional polyacrylamide gel electrophoresis than has been encountered in studies of serum transport proteins and erythrocyte enzymes with one-dimensional electrophoresis. Technical factors appear to account for only part of the difference. The two remaining (nonexclusive) explanations are more stringent biological selection against variants of these proteins or lower mutation rates at the loci encoding the proteins visualized with two-dimensional electrophoresis. While the former possibility cannot be rigorously excluded, the evidence suggests the latter hypothesis merits serious consideration. Some consequences of this latter suggestion for genetic monitoring and the interpretation of molecular evolution are mentioned. PMID- 2315303 TI - Multiple conductance classes of mouse nicotinic acetylcholine receptors expressed in Xenopus oocytes. AB - Acetylcholine receptor (AcChoR) subunit mRNAs transcribed from mouse BC3H-1 cDNAs were injected into Xenopus oocytes and the expressed AcChoR channels were examined by single channel recording. Injection of alpha-, beta-, gamma-, and delta-subunit mRNAs produced two predominant channel classes with conductances of approximately 50 and approximately 12 pS, while infrequent openings of approximately 25-pS channels were also observed. Injection of alpha-, beta-, and gamma-subunit mRNAs produced a single class of approximately 12-pS AcChoR channels, which resembled the smallest conductance channels present in alpha beta gamma omega-injected oocytes. Assembly of delta-less channels may thus explain the lowest conductance AcChoR channels in alpha beta gamma delta-injected oocytes and might also account for similar channels that have been observed in vertebrate skeletal muscle. PMID- 2315304 TI - Characterization of the transverse relaxation rates in lipid bilayers. AB - The 2H NMR transverse relaxation rates of a deuterated phospholipid bilayer reflect slow motions in the bilayer membrane. A study of dimyristoyl lecithin specifically deuterated at several positions of the hydrocarbon chains indicates that these motions are cooperative and are confined to the hydrocarbon chains of the lipid bilayer. However, lipid head group interactions do play an important role in modulating the properties of the cooperative fluctuations of the hydrocarbon chains (director fluctuations), as evidenced by the effects of various lipid additives on the 2H NMR transverse relaxation rates of the dimyristoyl lecithin bilayer. PMID- 2315305 TI - Presence of a vertebrate fibrinogen-like sequence in an echinoderm. AB - Sequence comparisons of the three homologous polypeptide chains that compose vertebrate fibrinogens imply that the molecule evolved before the divergence of vertebrates and invertebrates, but, to our knowledge, no protein resembling vertebrate fibrinogen has even been reported from an invertebrate. We used primers based on sequences conserved between lamprey and human fibrinogens and applied the polymerase chain reaction (PCR) to cDNA preparations from various invertebrates. A fibrinogen-like sequence was identified in cDNA prepared from the soft tissues of a sea cucumber, parastichopus parvimensis. The PCR-prepared material was then used to clone two closely related mRNA sequences from a sea cucumber soft tissue cDNA library. The putative fibrinogen-related proteins, FReP A and FReP-B, correspond to the carboxyl-terminal two-thirds of vertebrate fibrinogen beta and gamma chains. Computer comparisons of various fibrinogen related sequences indicate that the sea cucumber proteins diverged before the beta-gamma gene duplication. PMID- 2315306 TI - Genesis by meiotic unequal crossover of a de novo deletion that contributes to steroid 21-hydroxylase deficiency. AB - The HLA-linked human steroid 21-hydroxylase gene CYP21B and its closely homologous pseudogene CYP21A are each normally located centromeric to a fourth component of complement (C4) gene, C4B and C4A, respectively, in an organization suggesting tandem duplication of a ca. 30-kilobase DNA unit containing a CYP21 gene and a C4 gene. Such an organization has been considered to facilitate gene deletion and addition events by unequal crossover between the tandem repeats. We have identified a steroid 21-hydroxylase [steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10] deficiency patient who has a maternally inherited disease haplotype that carries a de novo deletion of a ca. 30-kilobase repeat unit including the CYP21B gene and associated C4B gene. This disease haplotype appears to have been generated as a result of meiotic unequal crossover between maternal homologous chromosomes. One of the maternal haplotypes is the frequently occurring HLA-DR3, B8, A1 haplotype that normally carries a deletion of a ca. 30-kilobase unit including the CYP21A gene and C4A gene. Haplotypes of this type may possibly act as premutations, increasing the susceptibility of developing a 21-hydroxylase deficiency mutation by facilitating unequal chromosome pairing. PMID- 2315307 TI - Cloning and sequence analysis of the cDNA for arachidonate 12-lipoxygenase of porcine leukocytes. AB - The complete amino acid sequence of arachidonate 12-lipoxygenase (EC 1.13.11.31) of porcine leukocytes was deduced by cloning and sequence analysis of DNA complementary to its mRNA. The sequence was confirmed by automated Edman degradation of the N-terminal regions of the native enzyme and its proteolytic fragments. The cDNA had an open reading frame encoding 662 amino acid residues with a calculated molecular weight of 74,911. Amino acid residues 533-545, Cys (Xaa)3-Cys-(Xaa)3-His-(Xaa)3-His, showed significant homology to the short cysteine- or histidine-containing sequences proposed as the metal-binding domains of transcription factors and various metal-containing proteins [Berg, J. M. (1986) Science 232, 485-487]. The amino acid sequence of 12-lipoxygenase exhibited 86% identity with human reticulocyte 15-lipoxygenase and showed 41% identity with human leukocyte 5-lipoxygenase. The 12-lipoxygenase cDNA recognized a 3.4-kilobase mRNA species in various porcine cell types, with the largest amount in leukocytes, followed by pituitary, lung, jejunum, and spleen. PMID- 2315308 TI - Isolation and characterization of a cDNA clone encoding avian skeletal muscle C protein: an intracellular member of the immunoglobulin superfamily. AB - C-protein is a thick filament-associated protein located in the crossbridge region of vertebrate striated muscle A bands. Its function is unknown. To improve our understanding of its primary structure, we undertook the molecular cloning of C-protein mRNA. We describe the isolation and characterization of a cDNA clone, lambda C-86, that encodes approximately 80% of the fast isoform of C-protein in the chicken. Sequence analysis of the insert revealed that C-protein, although an intracellular, nonmembrane-associated protein, is a member of the immunoglobulin superfamily. Like several cell surface adhesion molecules that belong to this superfamily, C-protein contains sequence motifs that resemble immunoglobulin domains and fibronectin type III repeats. Computer searches using the C-protein sequence also lead to the identification of related domains in chicken smooth muscle myosin light chain kinase that have not been reported previously. PMID- 2315309 TI - Concerted evolution of class I genes in the major histocompatibility complex of murine rodents. AB - Full-length cDNA sequences of two class I major histocompatibility complex molecules from the DA strain of Rattus norvegicus are reported. One codes for the classical class I restriction element RT1.Aa, which maps to the locus in the rat major histocompatibility complex homologous to H-2K in the mouse. The other probably codes for a soluble nonclassical class I molecule present in DA rat serum; a short deletion in the fifth exon implies that the translated product will terminate in the membrane-spanning region. These sequences have been compared with mouse classical class I sequences as well as with three published rat class I cDNA partial sequences. The results show, first, that "locus specific" substitutions from the H-2K, H-2D, and H-2L data set are scrambled in the RT1.Aa molecule; a majority of these substitutions have H-2D/L-specific features. Second, the data show that the four rat sequences are strikingly similar to one another regardless of locus or haplotype of origin; they share a number of apparently species-specific features that distinguish them all from mouse classical class I sequences, which likewise share distinctive features of their own. The results suggest that segmental sequence exchange plays a major role in determining the evolution of sequence in class I major histocompatibility complex molecules. PMID- 2315310 TI - Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats. AB - High-affinity nuclear binding sites for 17 beta-estradiol (17 beta E2) were recently found in bone cells; however, the mechanism by which estrogen exerts its effect on bone in vivo is still unknown. To study if estrogen acts on bone directly, we used an experimental model in which test substances are infused locally into rat femur trabecular bone. Sprague-Dawley rats weighing 150-160 g were ovariectomized (OVX) and 14 days later a polyethylene tube (1 mm in diameter) connected to an Alzet osmotic minipump was implanted into the distal femur 9 mm from the joint. 17 beta E2 (24 microliters/day at 0.01-1 nM), 17 alpha estradiol (17 alpha E2) (24 microliters/day at 1 nM), or phosphate-buffered saline (NaCl, 8 g/liter; KCl, 0.2 g/liter; KH2PO4, 0.2 g/liter; Na2HPO4.7H2O, 2.16 g/liter) was infused for 8 days. The contralateral limb remained intact. Animals were sacrificed and bones were examined by histomorphometry. Ovariectomy caused a 50% loss in trabecular bone volume (TBV) in the secondary spongiosa (from 20.3% +/- 1.7% to 9.6% +/- 1.1%; mean +/- SEM), a 2-fold increase in osteoclast number (to 4.0 +/- 0.4 per mm), a 3-fold increase in relative resorption surfaces (to 24.8% +/- 2.9%), a 9-fold increase in osteoblast number (to 11.3 +/- 2.1 per mm), and an 8-fold increase in relative osteoid surface (to 9.6% +/- 1.7%). The local infusion of 17 beta E2 for 8 days into OVX rats (i) restored the TBV dose dependently to 75% and 85% of control (non-OVX) levels, at 0.1 nM and 1 nM 17 beta E2, respectively; (ii) decreased osteoclast number and the relative resorption surface to control (non-OVX) levels; and (iii) further increased osteoblast number and the relative osteoid surface dose dependently (by 5-fold at 1 nM 17 beta E2). Phosphate-buffered saline infusion was without effect. Infusion of 17 alpha E2 had no effect on TBV, osteoclast number, or resorption surface but increased slightly the osteoblast number and the osteoid surface. Its potency was 1/100 that of 17 beta E2. The local infusion of 17 beta E2 or 17 alpha E2 had no effect on body or uterine weight. We conclude from these findings that estrogen delivered directly to the bone of OVX rats in vivo at 2.4 and 24 fmol/day acted locally to inhibit bone resorption and stimulate bone formation. PMID- 2315311 TI - Increased platelet-derived growth factor A-chain expression in human uterine smooth muscle cells during the physiologic hypertrophy of pregnancy. AB - Platelet-derived growth factor (PDGF) has been implicated in the cell proliferation and directed cell movement in various physiologic and pathologic processes. To explore the role of PDGF in a reversible physiologic process, adaptation of the uterus to pregnancy, expression of PDGF in tissue sections of human gestational myometrium was demonstrated by immunohistochemical techniques and confirmed by nuclease protection analysis. Commensurate with an increase in immunoreactive PDGF expression in the myometrial smooth muscle cells, increased levels of PDGF A-chain mRNA, but not PDGF B-chain or PDGF B-type receptor transcripts, were seen in the gravid uterus relative to the nongravid uterus. The amount of A-chain transcript increased during gestation and diminished during the puerperium. These observations demonstrate PDGF polypeptide expression in situ and implicate PDGF in a normal physiologic process--uterine expansion during pregnancy. PMID- 2315312 TI - Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11. AB - The MYOD1 locus is preferentially expressed in skeletal muscle and at higher levels in its related neoplasm, rhabdomyosarcoma. We have combined physical mapping of the human locus with meiotic and physical mapping in the mouse, together with synteny homologies between the two species, to compare the physical relationship between MYOD1 and the genetically ascertained human rhabdomyosarcoma associated locus. We have determined that the myogenic differentiation gene is tightly linked to the structural gene for the M (muscle) subunit of lactate dehydrogenase in band p15.4 on human chromosome 11 and close to the p and Ldh-1 loci in the homologous region of mouse chromosome 7. Because the rhabdomyosarcoma locus maps to 11p15.5, MYOD1 is very unlikely to be the primary site of alteration in these tumors. Further, these analyses identify two syntenic clusters of muscle-associated genes on the short arm of human chromosome 11, one in the region of rhabdomyosarcoma locus that includes IGF2 and TH and the second the tightly linked MYOD1 and LDHA loci, which have been evolutionarily conserved in homologous regions of both the mouse and the rat genomes. PMID- 2315313 TI - Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis. AB - Serotonin (5-HT) stimulated the release of arachidonic acid in hippocampal neurons cocultured with glial cells but not in glial cultures alone. Similar results were observed for the 5-HT-stimulated release of inositol phosphates. These results suggest a neural but not glial origin of both responses. Pharmacological studies suggested that release of arachidonic acid and inositol phosphates was mediated by a type 2 5-HT (5-HT2) receptor. 5-HT-stimulated release of arachidonic acid was also detected in cortical neurons, which contain high levels of 5-HT2 receptors, but not striatum, spinal cord, or cerebellar granule cells, which have very low levels or are devoid of 5-HT2 receptors. The phorbol ester phorbol 12-myristate 13-acetate augmented the 5-HT-stimulated release of arachidonic acid but inhibited the 5-HT-stimulated release of inositol phosphates. 5-HT-stimulated release of arachidonic acid, but not inositol phosphates, was dependent on extracellular calcium. 5-HT stimulated the release of [3H]lysophosphatidylcholine from [3H]choline-labeled cells with no increase in the release of [3H]choline or phospho[3H]choline. These data suggest that 5-HT stimulated the release of arachidonic acid in hippocampal neurons through the activation of phospholipase A2, independent of the activation of phospholipase C. PMID- 2315314 TI - Recombinant human bone morphogenetic protein induces bone formation. AB - We have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 micrograms of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans. PMID- 2315315 TI - Structure of nogalamycin bound to a DNA hexamer. AB - The anthracycline antibiotic nogalamycin, which binds to DNA, is composed of a planar aglycone substituted on each end to form an unusual dumbbell-shaped molecule. At one end nogalamycin contains an uncharged nogalose sugar and a methyl ester. At the other end nogalamycin contains a positively charged bicyclo amino sugar. We report the crystal structure of nogalamycin bound to the self complementary DNA hexamer d(m5CGTsAm5CG). In this complex, the cytosines are methylated at the 5 position and the DNA contains a phosphorothioate linkage at the TpA step. Two nogalamycin molecules bind to the 6-base-pair fragment of double-helical DNA. The drug has threaded between the phosphodiester backbones with three aromatic rings intercalated within the DNA. In the major groove, the bicyclo amino sugar forms two direct hydrogen bonds to span a CG base pair and interacts indirectly with the next base pair of the duplex via a water-mediated hydrogen bond. In the minor groove, a carbonyl oxygen of nogalamycin forms a hydrogen bond directly to N2 of a guanine. The DNA base pairs are severely buckled by up to 26 degrees and are also distorted in directions perpendicular to the Watson-Crick hydrogen bonds. This complex illustrates the deformable nature of DNA. PMID- 2315316 TI - Mitochondrial genotype of a unisexual salamander of hybrid origin is unrelated to either of its nuclear haplotypes. AB - We examined mitochondrial DNA (mtDNA), enzyme, and morphological variation among 17 unisexual Ambystoma of hybrid origin. Electrophoretic comparison of diagnostic enzymes indicates that these unisexuals are triploid with two nuclear genomes from the bisexual species Ambystoma laterale and one from Ambystoma jeffersonianum; however, according to restriction analysis, the mtDNAs of these specimens derive from a third species, Ambystoma texanum. This unusual situation is apparently due to a partially independent segregation event in an ancestor of these unisexuals. This situation highlights the potential importance of molecules with different inheritance patterns in elucidating complex cases of reticulate evolution. PMID- 2315317 TI - Functional analysis of the human tissue factor promoter and induction by serum. AB - Tissue factor (TF) is the primary initiator of the coagulation protease cascades. This cell surface glycoprotein is the receptor and essential cofactor for the serine protease factor VIIa. TF is constitutively expressed in some extravascular cell types and is transiently induced in monocytes, endothelial cells, and fibroblasts. Inducible expression is implicated in cellular immune responses, inflammation, and intravascular coagulation. Transcriptional regulation of the TF promoter was analyzed in COS-7 cells under conditions of (i) high-level expression and (ii) serum induction. The region comprising nucleotides -209 to +121 (relative to the transcription start site) supports high-level transcriptional activity and can be divided into two distinct regions: a region ( 111 to +121) that exhibited low promoter activity and a region (-209 to -112) that enhanced transcriptional activity to a high level. The role of further upstream sequences is still to be established, although two consensus binding sites for the transcriptional activator protein AP-1 did enhance low-level promoter activity. In serum-starved COS-7 cells TF expression was transiently increased 20-fold by serum. All transcriptionally active constructs were responsive to serum, indicating the presence of at least one serum response element, whose function was retained in the immediate 5' aspect of the gene, at 111 to +14. Based on this functional map, we propose that the elaborate pattern of TF expression by cells results from a relatively complex promoter. PMID- 2315318 TI - Immunolocalization in three dimensions: immunogold staining of cytoskeletal and nuclear matrix proteins in resinless electron microscopy sections. AB - We describe two methods for staining resinless thin sections with antibodies and gold-conjugated second antibodies. Immunolocalization of specific proteins is a powerful tool for cell structure studies but current techniques do not develop its full potential. Immunofluorescence provides only low-resolution localization, whereas conventional thin-section electron microscopy images and immunostains only the section surface. Resinless sections of extracted cell structures offer a simple and effective means of immuno-electron microscopy. Without embedding plastic or soluble proteins, the cell cytostructure produces high-contrast, three dimensional images. Resinless sections of detergent-extracted cells are prepared by embedding in diethylene glycol distearate, sectioning, and removing diethylene glycol distearate before microscopy. In the first method of immunostaining, extracted cells were fixed and stained with antibodies before embedment, sectioning, removal of the embedding resin, and critical point drying. In the postembedment method, the sample was embedded and sectioned, the diethylene glycol distearate was removed, and the sample was rehydrated before antibody staining. With these techniques, specific proteins were localized with high resolution throughout the entire section. Stereoscopic micrographs of resinless sections revealed the precise localization of specific cytoskeleton and nuclear matrix proteins in three dimensions with unprecedented clarity. PMID- 2315319 TI - Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. AB - An unusual pattern in a nucleic acid or protein sequence or a region of strong similarity shared by two or more sequences may have biological significance. It is therefore desirable to know whether such a pattern can have arisen simply by chance. To identify interesting sequence patterns, appropriate scoring values can be assigned to the individual residues of a single sequence or to sets of residues when several sequences are compared. For single sequences, such scores can reflect biophysical properties such as charge, volume, hydrophobicity, or secondary structure potential; for multiple sequences, they can reflect nucleotide or amino acid similarity measured in a wide variety of ways. Using an appropriate random model, we present a theory that provides precise numerical formulas for assessing the statistical significance of any region with high aggregate score. A second class of results describes the composition of high scoring segments. In certain contexts, these permit the choice of scoring systems which are "optimal" for distinguishing biologically relevant patterns. Examples are given of applications of the theory to a variety of protein sequences, highlighting segments with unusual biological features. These include distinctive charge regions in transcription factors and protooncogene products, pronounced hydrophobic segments in various receptor and transport proteins, and statistically significant subalignments involving the recently characterized cystic fibrosis gene. PMID- 2315321 TI - Activation of resting human T cells requires prolonged stimulation of protein kinase C. AB - Purified resting human T cells can be induced to express the alpha subunit of the interleukin 2 receptor and to proliferate by treatment with 12-O tetradecanoylphorbol-13-acetate plus ionomycin but not with 1,2 dioctanoylglycerol plus ionomycin. Determination of the translocation of protein kinase C showed that 12-O-tetradecanoylphorbol-13-acetate plus ionomycin caused a prolonged membrane association of the enzyme for more than 4 hr, whereas 1,2 dioctanoylglycerol plus ionomycin induced a transient membrane association, which was maximal at 20 min. Delivery of multiple additions of 1,2-dioctanoylglycerol plus ionomycin to the T cells resulted in progressively increased expression of the alpha subunit of the interleukin 2 receptor and proliferation commensurate with the number of multiple additions delivered, suggesting that prolonged protein kinase C activity is required for T-cell activation. PMID- 2315320 TI - Regulatory and structural motifs of chicken gizzard myosin light chain kinase. AB - The amino acid sequence for chicken smooth muscle myosin light chain kinase (smMLCK) was deduced from a full-length cDNA. This has allowed definition of both the complete sequence of the inactive 64-kDa proteolytic fragment, which contains the pseudosubstrate autoregulatory sequence, and of the active 61-kDa Ca2+/calmodulin-independent fragment, which lacks the autoregulatory domain. Comparison of the two sequences shows that the autoregulatory domain extends from Asn-780 to Arg-808. The peptide Leu-774 to Ser-787 does not inhibit smMLCK, whereas peptides of similar or shorter length from the pseudosubstrate region (Ser-787 to Val-807) are potent inhibitors. These data define the autoregulatory region as being contained within and probably identical to the pseudosubstrate domain. The catalytic and regulatory regions are flanked by several copies of 100 amino acid segments containing one of two consensus motifs. These motifs are absent from mammalian skeletal muscle MLCK or from Dictyostelium discoideum MLCK but are present in the Caenorhabditis elegans unc-22 gene product and the titin molecule of skeletal muscle myofibrils. These results indicate that the amino acid sequence of smMLCK encodes multiple functional motifs in addition to the catalytic domain. PMID- 2315322 TI - Secretin: structure of the precursor and tissue distribution of the mRNA. AB - Secretin is a 27-amino acid gastrointestinal hormone that stimulates the secretion of bicarbonate-rich pancreatic fluid. The unusually high number of serine, leucine, and arginine residues in secretin has precluded the use of oligonucleotides to screen cDNA libraries to isolate a secretin cDNA. In the present study, a short cDNA encoding porcine secretin was amplified from duodenal mucosal first-strand cDNA template by using 16,384- and 4096-fold degenerate primers in the DNA polymerase chain reaction. From the sequence of the amplified cDNA, an unambiguous oligonucleotide probe was designed to screen a cDNA library. Here we report the sequences of cDNAs encoding the porcine and rat secretin precursors. The predicted amino acid sequences reveal that each precursor consists of a signal peptide, an N-terminal peptide, secretin, and a 72-amino acid C-terminal peptide. Secretin has been highly conserved through evolution. Rat secretin differs from its porcine counterpart by a single glutamine-for arginine substitution at position 14. In contrast, the amino acid sequences of the C-terminal peptides are only 39% conserved between the two species, suggesting that the C-terminal peptide does not have an essential physiologic function. RNA blot hybridizations reveal that the rat secretin gene is expressed throughout the small intestine. Although secretin immunoreactivity has been localized in the central nervous system by some laboratories, we are unable to detect secretin mRNA in tissues of the central nervous system by Northern blot hybridization. PMID- 2315323 TI - Sustained metabolic scope. AB - Sustained metabolic rates (SusMR) are time-averaged metabolic rates that are measured in free-ranging animals maintaining constant body mass over periods long enough that metabolism is fueled by food intake rather than by transient depletion of energy reserves. Many authors have suggested that SusMR of various wild animal species are only a few times resting (basal or standard) metabolic rates (RMR). We test this conclusion by analyzing all 37 species (humans, 31 other endothermic vertebrates, and 5 ectothermic vertebrates) for which SusMR and RMR had both been measured. For all species, the ratio of SusMR to RMR, which we term sustained metabolic scope, is less than 7; most values fall between 1.5 and 5. Some of these values, such as those for Tour de France cyclists and breeding birds, are surely close to sustainable metabolic ceilings for the species studied. That is, metabolic rates higher than 7 times RMR apparently cannot be sustained indefinitely. These observations pose several questions: whether the proximate physiological causes of metabolic ceilings reside in the digestive tract's ability to process food or in each tissue's metabolic capacity; whether ceiling values are independent of the mode of energy expenditure; whether ceilings are set by single limiting physiological capacities or by coadjusted clusters of capacities (symmorphosis); what the ultimate evolutionary causes of metabolic ceilings are; and how metabolic ceilings may limit animals' reproductive effort, foraging behavior, and geographic distribution. PMID- 2315324 TI - Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease. AB - Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, we developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py+/Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hematopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeat (Mo-MLV LTR) and levels of Py+/Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection (by means of the polymerase chain reaction) of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py+/Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity had been normalized. PMID- 2315325 TI - Long-term transplantation of canine keratinocytes made resistant to G418 through retrovirus-mediated gene transfer. AB - We studied cultured canine keratinocytes to determine whether they could serve as targets for retrovirus-mediated gene transfer and whether infected cells could persist after transplantation into dogs, a large random-bred model for gene transfer studies. Canine keratinocytes obtained from skin biopsy samples were cultured in vitro with lethally irradiated NIH 3T3 cells used as a feeder layer. The keratinocyte colonies consisted of squamous epithelium with numerous desmosomes, tonofilaments, and keratohyalin granules. In addition, the cells were strongly reactive with monoclonal antibodies to cytokeratin intermediate filament proteins. For the infection studies, we grew the keratinocytes on a feeder layer of lethally irradiated PA317 retrovirus packaging cells, which produced a helper free amphotropic retroviral vector containing the neomycin phosphotransferase (neo) gene. After cocultivation, 34% (range, 10-76%) of the keratinocytes were found to be resistant to the neomycin analogue G418. Infected keratinocytes were then transplanted into the dog of origin; 1% (range, less than 0.1-3%) of the keratinocytes obtained 27-130 days after transplantation from skin biopsy samples gave rise to G418-resistant colonies. We conclude that canine keratinocytes cultured in vitro can be infected efficiently with a neo gene-containing retroviral vector, and they show persistent G418 resistance for at least 130 days after transplantation into the skin donor. PMID- 2315326 TI - FlbD of Caulobacter crescentus is a homologue of the NtrC (NRI) protein and activates sigma 54-dependent flagellar gene promoters. AB - The periodic transcription of flagellar genes in the Caulobacter crescentus cell cycle is controlled, in part, by their organization in a regulatory hierarchy. The flbG (hook operon), flaN, and flagellin gene operons, which are at the lowest levels of the hierarchy and expressed late in the cell cycle, contain Ntr-like promoters. We report that flbD, one of the early genes required in trans for expression of these operons, codes for a 52-kDa protein homologous to the transcriptional activators NtrC (NRI), NifA, DctD, HydG, and XylR. Our results show that in Escherichia coli flbD partially complements glnG (ntrC) mutations and stimulates transcription of the C. crescentus sigma 54 RNA polymerase dependent flbG gene. Additionally, the sequence predicts that FlbD protein, along with NtrC, DctD, and HydG proteins, is structurally related at the amino-terminal domain to a larger family of response regulators that mediate cellular responses to environmental stimuli. FlbD may be a singular member of this large protein family in that its function is tied to an internal cell-cycle signal. FlbD is also unusual in that its amino-terminal domain contains only one of the three residues conserved in previously described members of this family of response regulators. PMID- 2315328 TI - Let nurses be an effective weapon against drug abuse. PMID- 2315327 TI - Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA. AB - Envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) is known to inhibit T-cell function, but little is known about the mechanisms of this immunosuppression. Pretreatment of a CD4+ tetanus toxoid-specific T-cell clone with soluble gp120 was found to exert a dose-dependent inhibition of soluble antigen-driven or anti-CD3 monoclonal antibody-driven proliferative response, interleukin 2 (IL-2) production, and surface IL-2 receptor (IL-2R) alpha-chain expression, all of which were reversed by the addition of exogenous IL-2. mRNA for the gene encoding IL-2 was suppressed by treatment with gp120, but IL-2R gene transcription was not inhibited. Bypass activation of the T-cell clone with phorbol 12-myristate 13-acetate plus ionomycin was unaffected by gp120 pretreatment. Thus, gp120-CD4 interaction interferes with an essential role of the CD4 molecule in signal transduction through the CD3-antigen receptor (Ti) complex. Such a mechanism of gp120-induced immunosuppression, if operative in vivo, could contribute to the depressed specific immune responses associated with HIV infection. PMID- 2315329 TI - Nursing care of catheterised patients. AB - Catheterised patients are at a relatively high risk of complications and infection. This risk can be greatly reduced by excellent nursing care. PMID- 2315330 TI - The risks of i.v. therapy. AB - Infection rates in IV therapy are unacceptably high, but how can they be reduced and who should reduce them? This article begins a series on preventing infection in IV therapy. PMID- 2315331 TI - Psychoanalysis and dynamic psychotherapy. AB - Analytic therapists work with a wide range of clients, taking an active role in helping them overcome problems which often stem from their childhood. PMID- 2315332 TI - Using modern dressings to effect debridement. AB - Before sloughy or necrotic wounds can begin to heal, they must be debrided. Some of the modern wound dressings are not only extremely effective in this, but they do not damage surrounding tissue. PMID- 2315333 TI - Why do we forget to remember handwashing? PMID- 2315334 TI - Resource management in action on the ward. AB - The implementation of resource management at the Radcliffe Infirmary made clinical managers responsible for their ward budgets. This article describes how a nursing system was developed to facilitate the planning and management of resources at ward level. PMID- 2315335 TI - What about the relatives? AB - Dealing with a relative or friend's terminal illness is an extremely stressful experience. How well are patients' relatives and friends cared for by healthcare staff? PMID- 2315336 TI - SCBU (special care baby unit): keeping the baby breathing. AB - Beginning a major new series on special baby care, this article looks at the types of unit, the babies treated in them, and how respiration is maintained. PMID- 2315337 TI - Coming out of my no-man's land. PMID- 2315338 TI - Mouse liver carcinogenesis: mechanisms and species comparisons. Proceedings of a symposium. Austin, Texas, November 30-December 3, 1988. PMID- 2315339 TI - Structural and immunological identity of p65 tumor-associated factors from rat and mouse hepatocarcinomas. PMID- 2315340 TI - DNA adduct formation in relation to tumorigenesis in mice chronically fed 2 acetylaminofluorene. PMID- 2315341 TI - Do mouse liver tumors predict rat tumors? A study of concordance between tumors induced at different sites in rats and mice. PMID- 2315342 TI - The androgen receptor and liver tumor development in mice. PMID- 2315343 TI - Heme metabolism in hepatocellular carcinoma. PMID- 2315344 TI - Gap-junctional intercellular communication and murine hepatic carcinogenesis. PMID- 2315345 TI - Oval cells and liver carcinogenesis: an analysis of cell lineages in hepatic tumors using oncogene transfection techniques. PMID- 2315346 TI - Acute hyperplasia and peroxisome proliferation induced by methylclofenapate: a species comparison and implications for liver carcinogenesis. PMID- 2315347 TI - Research opportunities and reducing uncertainty. PMID- 2315348 TI - Buspirone blocks the discriminative stimulus effects of apomorphine in monkeys. AB - Three rhesus monkeys were trained to discriminate apomorphine (APO) from saline in a two-lever, food-reinforced drug discrimination procedure. After acquisition of the discrimination, the monkeys were given various doses of APO in combination with saline or buspirone before test sessions in which responses occurring on either lever were reinforced. Combinations of APO (0.01-0.08 mg/kg, IV) and saline resulted in a dose-related increase from 0 to 100% in the percentage of responses that occurred on the APO-appropriate lever. When buspirone (0.04-0.16 mg/kg, IV) was combined with APO, reductions from 100% to 0% APO-appropriate responding were seen following at least one dose combination in all three monkeys. A parallel shift to the right of the APO dose-response curve with buspirone was evident in 2 monkeys, indicating surmountable antagonism. In one case, a further increase in buspirone dose resulted in an insurmountable antagonism, i.e., increasing APO dose still resulted in primarily saline appropriate responding. These results suggest that buspirone can function as a D2 dopamine (DA) receptor antagonist at behaviorally relevant doses. PMID- 2315349 TI - Latency to enter a mirrored chamber: a novel behavioral assay for anxiolytic agents. AB - Many animal species exhibit approach-avoidance responses upon the novel placement of a mirror into an individual animal's environment. With a view toward identifying new behavioral measures with qualitatively or quantitatively different responses to anxiolytic agents, we developed a mirrored chamber apparatus for which adult male BALB/cByJ mice showed an extended latency to enter. Administration of diazepam significantly reduced this latency to enter a mirrored chamber in a dosage-dependent manner. The psychomotor stimulant, methylphenidate, had no effect on latency to enter the mirrored chamber at a dose which stimulated locomotor activity to the same extent as diazepam. Thus, the decreased latency to enter the mirrored chamber brought about by diazepam seems unlikely to reflect the motor effects of this benzodiazepine. The potency of diazepam was significantly lower in the mirrored chamber assay than it was on three other measures of exploratory activity--"head-dipping" performance, plus maze performance and locomotor activity stimulation. The findings of our study indicate that the mirrored chamber method is simple to carry out, nonpunishing, rapid and quantitative and that it possesses pharmacological attributes which distinguish its response to anxiolytics from other assays of exploratory behavior. PMID- 2315350 TI - Amino acids and memory consolidation in the cricket. I: Changes in the titer of free amino acids in nervous tissue after learning. AB - The involvement of certain amino acids in the memory consolidation process was investigated in the cricket Pteronemobius sp. Thirsty crickets were trained to constantly turn to one side of a symmetrical Y-shaped maze using reinforcement with water. Controls were trained to turn to both sides of the maze according to a random program. Animals were sacrificed immediately after training and free amino acid fractions were isolated from whole brain, subesophagic, prothoracic, mesothoracic and metathoracic ganglia homogenates and analyzed by high pressure liquid chromatography. A complex pattern of variation in the titer of amino acids emerged after learning, where the changes differed among the various ganglia. The most conspicuous change was an increase in the levels of urea and an amino acid like compound related to the urea cycle, in all ganglia except the subesophagic one, if compared to controls. Arginine increased in the subesophagic ganglion, but decreased significantly in the metathoracic ganglion. The variation of ganglionic amino acid levels and its possible relation to mnemonic processes is discussed. PMID- 2315351 TI - Pertussis toxin inhibits morphine analgesia and prevents opiate dependence. AB - Six days after intracerebroventricular pretreatment of rats with pertussis toxin (PTX 0.5 microgram/rat) there was a marked decrease in the antinociceptive effect of morphine, regardless of the route of opioid administration (into the periaqueductal gray matter, intrathecally or intraperitoneally) or the analgesic test used (tail flick and jaw opening reflex). PTX pretreatment also partially attenuated the naloxone-precipitated withdrawal syndrome in morphine-dependent rats, significantly reducing teeth chattering, rearing and grooming. These in vivo findings indicate that G-protein-dependent mechanisms are involved in morphine analgesia and dependence. The biochemical mechanism could be related to ADP ribosylation of Gi coupled to the adenylate cyclase system, but an interaction of PTX with other G-proteins linked to different second messengers or directly to ionic channels cannot be excluded. PMID- 2315352 TI - Effects of caerulein and cholecystokinin-octapeptide on acetylcholine and choline contents in the brains of intact and vagotomized mice. AB - The effects of caerulein (CLN; 0.5, 5, and 50 micrograms/kg, IP) and cholecystokinin-octapeptide (CCK-8; 5, 50, and 400 micrograms/kg, IP) on the acetylcholine and choline contents in the discrete brain regions were examined, 30, 60, and 120 min after injection into intact and vagotomized mice. In all of the discrete brain regions of the intact mice. CLN and CCK-8 was found to have a complex effect on the acetylcholine and choline contents depending on the brain region, dosage and treatment time. On the other hand, the effect of CLN was abolished completely in the vagotomized mice. Thus, the present study indicates that peripherally administered CLN and CCK-8 have an effect on the central cholinergic system, mainly mediated via the vagus. PMID- 2315353 TI - Is there a genetic control of morphine preference in rat? AB - Morphine preference was tested in two-bottle, voluntary-choice situations on physically dependent Sprague-Dawley rats. The animals ingested morphine which was dissolved in a fluid diet. Choice tests were performed under similar experimental conditions as the ingestions. Approximately 10% of the physically dependent rats voluntarily preferred large amounts of morphine already after a short treatment. The preference level was found to correlate with the animals' requirement for the drug. There was a gradual increase in morphine preference in F1 and F2 offspring of extremely high morphine preference rats. In F3 (of such extremely high morphine preference rats) up to 65% died shortly after birth. The surviving rats showed a low morphine preference after ingestion when adult. Our result of increasing preference over two generations and death of a large number of rats in the third generation with a low morphine preference of the surviving rats was seen also in F4-F8. The data suggest that high morphine preference is under genetic control. PMID- 2315354 TI - Habituation and retention of the head-shake response: lack of impairment by nucleus basalis magnocellularis lesions. AB - Bilateral ibotenic acid lesions of the nucleus basalis magnocellularis (NBM) were examined on the habituation and retention of the head-shake response (HSR). HSR, a rapid, stereotyped rotation of the head about a front-to-rear axis, was elicited by a stream of mildly pressurized air directed at the ear in Fischer 344 rats. HSR training consisted of 40 stimulated trials followed by a 30-min retention test of 20 stimulated trials. Stimulus duration was 15 sec per trial with a 15-sec intertrial interval. Frontal cortex choline acetyltransferase was reduced by 22% in the NBM-lesioned group compared to the controls. The NBM lesioned rats and the controls were not significantly different on either frequency or latency measures of HSR habituation or retention. The results do not support a role for cortical cholinergic mediation of the HSR. PMID- 2315355 TI - Tryptophan-morphine interactions and postoperative pain. AB - Patients undergoing abdominal surgery were infused with saline or the 5 hydroxytryptamine (5-HT) precursor tryptophan starting in the operating room and continuing for three hours in the recovery room. There was a nonsignificant trend for patients who received tryptophan to have higher pain scores. In the saline treated patients, plasma tryptophan was below the range for normal healthy subjects, and there was a strong positive relationship between plasma tryptophan and morphine requirements. These data, taken together with animal data obtained using the formalin pain test, suggest that a 5-HT system in the brain can antagonize the dissociative state produced by morphine, which helps patients to tolerate pain. When plasma tryptophan falls below normal levels, brain 5-HT falls and morphine requirements are reduced. While tryptophan may potentiate spinal 5 HT function to decrease nociceptive afference in some circumstances, there may be clinical conditions in which the use of tryptophan is contraindicated. PMID- 2315356 TI - Strain differences in adrenalectomy-induced alterations in nicotine sensitivity in the mouse. AB - Adult mice of four inbred strains (A, BUB, C57BL, DBA) and two selectively bred lines [Long-Sleep (LS) and Short-Sleep (SS)] were tested for differences in glucocorticoid regulation of nicotine sensitivity. One week following adrenalectomy (ADX), animals were tested for nicotine sensitivity in a battery of tests that included acoustic startle response, Y-maze activity (line crosses and rearings), heart rate and body temperature. Although each type of animal tested had increased nicotine sensitivity in at least one of the test battery measurements, there was clear evidence for a genetic influence on the scope of ADX-induced changes in sensitivity. LS animals had the largest increase in sensitivity with altered responses in four of five tests following ADX. The sensitivity of DBA animals was increased in two tests while for A, BUB, C57BL and SS animals, only one test was affected. ADX-induced alterations in nicotine sensitivity could not be explained on the basis of changes in nicotinic receptor number since changes were consistent across strains. The mechanism by which ADX causes increased nicotine sensitivity is not known. However, these data support the hypothesis that nicotine sensitivity is modulated by adrenal glucocorticoid secretion and also suggest that this phenomenon is under strict genetic control. PMID- 2315357 TI - Effects of serotonin agonists on operant behavior in the squirrel monkey: quipazine, MK-212, trifluoromethylphenylpiperazine, and chlorophenylpiperazine. AB - The behavior of squirrel monkeys was studied under fixed-interval (FI) schedules with responding maintained either by food presentation or by termination of stimuli correlated with impending electric shock delivery (stimulus-shock termination). The 5-HT agonists m-trifluoromethylphenylpiperazine (TFMPP), m chlorophenylpiperazine (mCPP), and 6-chloro-2(l-piperazinyl)pyrazine (MK-212) decreased responding under both the food and shock schedules (0.3-5.6 mg/kg). These decreases in responding were blocked by the nonselective 5-HT antagonists methysergide and mianserin (0.3, 1.0 mg/kg), but not by the selective 5-HT2 antagonists ketanserin (0.3-1.7 mg/kg) or pirenperone (0.001-0.1 mg/kg). Quipazine (0.3-5.6 mg/kg) decreased responding under the food schedule, and this effect was blocked by both the nonselective and selective 5-HT2 antagonists. This pattern of antagonism suggests that the decreases in responding produced by quipazine involve significant actions at 5-HT2 sites, whereas those produced by TFMPP, mCPP, and MK-212 do not. In contrast to the decreases in responding seen with the food schedules, quipazine produced moderate increases in responding under the shock schedules. Moreover, these increases in responding were not blocked by methysergide or mianserin, but instead were enhanced. The results with antagonists suggest that certain behavioral effects of quipazine are probably due to actions at 5-HT2 sites, whereas similar effects of TFMPP, mCPP, and MK-212 are more related to actions at other 5-HT receptor subtypes. PMID- 2315358 TI - Schedule-induced cocaine drinking: choice between cocaine and vehicle. AB - Rats were exposed to daily 3-hr schedule-induced polydipsia sessions (fixed-time 1-min food-pellet delivery) with two drinking fluids available: cocaine solution and water. Fluid position was alternated daily. Polydipsia occurred mostly from a preferred-side spout (position preference) until cocaine solution concentration was increased to between 0.52 and 1.04 mg/ml and animals drank mostly water. Within a lower concentration range (0.28-0.6 mg/ml) maximum session cocaine intakes ranged from 54.3 to 120.1 mg/kg. Postsession serum cocaine levels were about 200 ng/ml. At individually chosen cocaine solution concentrations, the addition of saccharin to the solution did not increase cocaine intake, but a compound solution (saccharin plus glucose) did. With progressive dilution of the compound vehicle, an almost complete preference for cocaine solution was maintained. But with a return to water as the vehicle, animals reverted to a position preference after a few sessions, although one maintained a clear cocaine preference. Schedule-induced polydipsia produced chronic, oral self administration of cocaine resulting in pharmacologically significant intakes and serum levels. PMID- 2315359 TI - Tyrosine loading increases dopamine metabolite concentrations in the brain. AB - Administration of haloperidol (1.5 mg/kg) to rats increased concentrations of dopamine metabolites in the corpus striatum, nucleus accumbens, hypothalamus and amygdala. Treatment of similar rats with various doses (25, 100 or 400 mg/kg) of tyrosine methyl ester in combination with the haloperidol led to additional elevations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the corpus striatum and hypothalamus at the lowest dose tested. Therefore, it is concluded that during periods of increased neuronal activity, as induced by haloperidol, tyrosine availability may become a rate-limiting factor in dopamine metabolism. PMID- 2315360 TI - Adrenoreceptor antagonist treatment influences recovery of learning following medial septal lesions and hippocampal sympathetic ingrowth. AB - Previous studies have demonstrated that in male rats hippocampal sympathetic ingrowth (HSI), which is induced by medial septal lesions (MS), is detrimental to recovery of spatial learning. The present study was performed in an attempt to determine if this effect was mediated through adrenergic receptor activity. Adult male Sprague-Dawley rats underwent training on a modified version (i.e., 4 arms baited) of a radial-8-arm maze task. Following attainment of learning criterion animals underwent one of three surgical procedures: CON (sham surgeries); MSGx (MS + superior cervical ganglionectomy--to prevent HSI); MS (MS + sham ganglionectomy). Reacquisition trials were performed in the same manner as initial acquisition except animals were treated with vehicle, propranolol (20 mg/kg), or phentolamine (20 mg/kg) 30 minutes prior to testing. As expected, vehicle-treated MS animals took longer to reacquire the task than MSGx animals, who were in turn more impaired than CON animals. Propranolol (beta-adrenergic antagonist) treatment impaired performance of both the MS and MSGx group, but did not alter the CON group. Phentolamine (alpha-adrenergic antagonist) increased the number of trials to reattain criterion in the CON group, had no effect in the MSGx group, and markedly improved performance in the MS group. The results suggest that HSI mediates its detrimental effects through alpha-receptors, while beta-blockade, in the setting of brain injury, is detrimental to performance regardless of the presence or absence of HSI. PMID- 2315361 TI - [125I]-2-(2,5-dimethoxy-4-iodophenyl)aminoethane ([125I]-2C-I) as a label for the 5-HT2 receptor in rat frontal cortex. AB - Recent studies of 5-HT2 receptor binding have involved the use of radiolabeled agonists. This report describes the use of [125I]-2-(2,5-dimethoxy-4 iodophenyl)aminoethane ([125I]-2C-I) as a label for low-density 5-HT2 agonist binding sites. A nonhydrolyzable analog of GTP, GppNHp, was found to inhibit the high affinity binding of [125I]-2C-I. 5-HT and several 5-HT2 agonists and antagonists displayed high affinity for this site. In addition, a significant decrease in the Bmax value, but not the KD for [125I]-2C-I was observed at 37 degrees C as compared to that observed at 24 degrees C. Several structure activity relationships were investigated for displacement of [125I]-2C-I, and the results are consistent with the importance of this receptor in the mechanism of action of hallucinogens. This study demonstrates the utility of [125I]-2C-I as a novel radioligand and provides further data that the 5-HT2 receptor is significantly linked to hallucinogenic activity for several compounds. PMID- 2315362 TI - Inhibitory and stimulatory effects of morphine on locomotor activity in mice: biochemical and behavioral studies. AB - A possible interaction between the opposite effect (inhibition and stimulation) of morphine on locomotor activity in mice and monoaminergic systems in the striatum was studied. Ten minutes after systemic administration, morphine at 1.25 mg/kg decreased locomotor activity and the levels of 3-methoxytyramine (3-MT), whereas at 20 mg/kg locomotor activity and 3-MT levels increased. At the same time, no change in the other monoamine metabolite (DOPAC, HVA, MHPG, and 5-HIAA) levels was observed. Sixty minutes after administration, morphine at 1.25 mg/kg did not induce any change in locomotor activity or in all the monoamine metabolite levels measured. On the other hand, morphine at 20 mg/kg maintained an initial increase in locomotor activity and increased not only 3-MT levels, but also other metabolite (DOPAC, HVA, MHPG, and 5-HIAA) levels. These results suggest that, at low dosages, the inhibitory effect of morphine on locomotor activity in mice may be related to a decrease of the presynaptic dopamine release in the striatum and that the stimulatory effect of morphine, at high dosages, may be related to an increase of the presynaptic dopamine release in the striatum. PMID- 2315363 TI - Fluoxetine reduces intravenous cocaine self-administration in rats. AB - Rats self-administered intravenously delivered cocaine (0.2 mg/kg) under a fixed ratio (FR) 4 schedule during 24-hr sessions. Water was freely available from both a drinkometer and a standard water bottle. After behavior had stabilized, the rats were injected with fluoxetine HCl at 10:00 a.m. and 4:00 p.m. for 5 consecutive days. Three groups of 5 rats each received a different dose of fluoxetine (2.5, 5 or 10 mg/kg) via the IV cannula. In three other groups of rats a glucose and saccharin solution (G + S) was substituted for water in the automatic drinking device and saline was substituted for cocaine. These three groups of rats received the same fluoxetine doses as the cocaine self-injecting groups. In two additional groups of 5 rats each, the cocaine dose was changed to 0.1 or 0.4 mg/kg, and 5 mg/kg fluoxetine injections were given. The two higher doses of fluoxetine (5 and 10 mg/kg) reduced cocaine infusions (0.2 mg/kg) by at least 50 percent on all 5 days of treatment, and cocaine infusions returned to baseline levels within 48 hr after fluoxetine treatments were terminated. Behavior maintained by the G + S solution was also reduced by the two higher fluoxetine doses; however, this reduction did not reliably occur until the last two days of fluoxetine administration. The G + S intakes returned to baseline levels within 24 hr after fluoxetine treatment. Fluoxetine also reduced cocaine infusions in the group of rats that received the lower unit dose of cocaine (0.1 mg/kg); however, it had almost no effect on behavior maintained by a higher cocaine dose (0.4 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2315364 TI - Orally delivered cocaine as a reinforcer for rhesus monkeys. AB - Orally delivered cocaine was established as a reinforcer for six rhesus monkeys. Cocaine and its vehicle, water, were available from separate spouts under independent concurrent fixed-ratio schedules. The positions of cocaine and water were reversed between spouts from session to session. Cocaine consistently maintained higher response rates than water. Cocaine concentration was systematically varied for three of the six monkeys tested, and cocaine intake (mg of drug/kg of body wt.) increased with increases in drug concentration. PMID- 2315365 TI - Cocaine and level of arousal: effects on vigilance task performance of rats. AB - Rats were food-reinforced for pressing one of two levers in an operant chamber, with the correct lever being indicated by the position of a briefly illuminated light. After stable accuracy levels were achieved, the rats were tested after an injection of either saline or cocaine (2.5 mg/kg) under two conditions. In the "low arousal" condition, animals were tested during the light phase of a 12-hr light-dark cycle and were fed approximately 5 hr prior to testing. In the "high arousal" condition, animals were tested during the dark phase after approximately 28-hr food deprivation. As expected, accuracy was higher and median choice and food retrieval latencies were shorter under the high arousal condition. Contrary to predictions, cocaine enhanced accuracy under both conditions. These results indicate that cocaine-enhanced performance in some tasks is not necessarily dependent on the animal performing at suboptimal arousal levels. PMID- 2315366 TI - Gonadal alcohol and aldehyde dehydrogenase: in vivo and in vitro effects of psychoactive and endocrine agents. AB - The in vivo effect of amantadine, chlorpromazine and reserpine on testicular aldehyde dehydrogenase (T-ALDH) was studied as a function of mouse strain. The effect of Leu-enkephalin and tetrahydropapaverine on rodent T-ALDH was also studied in vivo. The in vitro effect of chlorpromazine, papaverine and scopolamine on rodent subcellular T-ALDH and testicular alcohol dehydrogenase (T ADH) were evaluated. A strain-linked difference in endogenous T-ALDH among the three mouse strains studied was determined. Individual injection of chlorpromazine or reserpine inhibited only albino ICR T-ALDH which was alleviated by pretreatment with amantadine and, thereby, suggesting antagonism between amantadine and these agents. The Leu-enkephalin administration induced T-ALDH from saline control. Tetrahydropapaverine did not influence the enzymes studied in vivo compared to an insignificant in vitro induction of T-ADH by the O methylated analogue papaverine. Chlorpromazine noncompetitively inhibited T-ADH in vitro. The results indicate the modulation of the enzymes studied, which are involved in both detoxification of ethanol and biogenic amine-derived aldehyde intermediates, by agents affecting the endocrine system. This suggests the potential of these testicular enzymes in the evaluation of alcohol- and drug induced endocrine adverse reactions. PMID- 2315367 TI - Free-running circadian activity rhythms during long-term clonidine administration in rats. AB - Experimental and clinical studies indicate that the alpha-adrenergic agonist clonidine can alter mood and activity. However, the behavioral effects of this agent are complex and appear to depend on duration of treatment. Recent work from this laboratory demonstrated that clonidine systematically alters the period, amplitude, and level of free-running circadian activity rhythms in rats. The present study confirms and extends previous observations by employing a longer duration of clonidine treatment. The results show that chronic clonidine administration reversibly shortens the free-running period and reduces the amplitude of the free-running rhythm in constant light. Furthermore, clonidine treatment can increase or decrease the level of activity, depending on baseline activity level, and these effects are not consistently reversed following the termination of treatment. These observations support the hypothesis that noradrenergic systems influence both the circadian periodicity and the level of spontaneous activity, and that clonidine may influence these two parameters by acting at different neural or neuronal loci. PMID- 2315368 TI - Effects of propranolol on, and noradrenergic correlates of, the response to nonreward. AB - Rats were rewarded by food for running in a straight runway with short (15 sec) intertrial intervals. On the final day, animals were subjected to either 14 extinction trials or 14 rewarded trials. During acquisition, half of each group had been injected once daily for 15 days with propranolol (5 mg/kg IP), the remainder with saline vehicle. All animals were killed immediately after the final trial and the cerebral cortex taken for noradrenaline assay and radioligand binding to beta- and alpha 2-adrenoceptors. Propranolol increased running times early in extinction; this effect was replicated in a second experiment. Neither the drug injections nor the extinction procedure affected neurochemical measures. However, the rate of extinction correlated positively with both beta- and alpha 2 adrenoceptor number. Although consistent with the theory that beta-adrenoceptors are involved in adaptation to stress, these results differ from our previous findings. The relationship between beta-adrenoceptor number and the response to stress may depend on the severity of the stress. PMID- 2315369 TI - Fluoxetine reduces food intake by a cholecystokinin-independent mechanism. AB - The selective serotonin uptake inhibitor, fluoxetine (3.0-10 mg/kg), produced a significant dose-related suppression of palatable food consumption in nondeprived rats. The anorectic effect of fluoxetine (10 mg/kg) was not reversed by the potent and highly selective cholecystokinin receptor antagonist MK-329 [1-methyl 3-(2-indolyl) amino-5-phenyl-3H-1,4-benzodiazepin-2-one], administered in doses of 10-100 micrograms/kg. Fluoxetine (10 mg/kg) also significantly reduced the consumption of powdered laboratory chow in a 6-hr nocturnal free-feeding test. The anorectic effect in this paradigm was also not antagonized by MK-329. In contrast to previous data for d-fenfluramine (which enhances serotonin release), these results indicate that fluoxetine may suppress food intake by a mechanism which is independent of endogenous cholecystokinin. PMID- 2315370 TI - Corticostriatal and thalamic regulation of amphetamine-induced ascorbate release in the neostriatum. AB - Lesions of cerebral cortex and ventromedial nucleus (VM) of the thalamus were made in rats to investigate the contribution of these structures to amphetamine (AMPH)-induced ascorbate (AA) release in the neostriatum as measured by in vivo voltammetry. Following a recovery period of at least one week, rats were anesthetized, and electrochemically modified, carbon-fiber electrodes were lowered into the neostriatum. Compared to data obtained from sham-operated and unoperated controls, bilateral aspiration lesions of cerebral cortex significantly lowered both the basal level of AA and the amount of AA released by AMPH in the neostriatum. Similar results were obtained after bilateral, but not unilateral electrolytic lesions of the VM thalamus. Collectively, these results suggest that the corticostriatal pathway and the VM thalamic nuclei participate in the regulation of basal and AMPH-induced AA release in the neostriatum. PMID- 2315371 TI - Failure of serotonin antagonist pizotifen to stimulate feeding or weight gain in free-feeding rats. AB - The serotonin antagonist pizotifen (BC-105) is prescribed as an appetite and weight enhancer (Mosegor--Wander, also commercialized under brand names Sanmigran or Sandomigran--Sandoz, Switzerland) for anorectic and convalescent humans. There has been, however, difficulty in demonstrating any orexigenic effect of pizotifen in laboratory animals. In the present report, the influence of chronic administration of pizotifen (0.1-30.0 mg/kg b.wt. per day, SC) on food intake and body weight gains was studied in rats given a standard diet (SD-energy content 14.5 kJ/g, 9% fibre), and in rats either habituated to a low energy content, carbohydrate-free diet (DD-7.3 kJ/g, 45% fibre), or given the DD after habituation to the SD. Pizotifen failed to increase food intake or weight gain. Nor did it shorten a period of initial depression of intake of the unfamiliar DD. On the contrary, pizotifen seemed to diminish food intake and weight gain in rats fed the low energy content diet. Since it has been reported that other 5-HT antagonists, e.g., cyproheptadine, methysergide, and ritanserin can enhance feeding, it is of some interest that pizotifen failed to affect food intake or weight gain in rats. The results suggest that the effects of pizotifen (and, possibly, of serotonin) in rats may differ from those in man. The possibility that feeding in the rat is mediated by 5-HT1 rather than 5-HT2 receptors is discussed. PMID- 2315372 TI - Centrally administered opioid antagonists, nor-binaltorphimine, 16-methyl cyprenorphine and MR2266, suppress intake of a sweet solution. AB - Three opioid antagonists (MR2266, 16-methyl cyprenorphine and nor binaltorphimine) were tested independently for their ability to suppress the intake of a highly palatable saccharin and glucose (S/G) solution after central administration. MR2266 is an equally potent antagonist at kappa (kappa) and mu (mu) opioid receptors. Nor-binaltorphimine (N-BNI) and 16-methyl cyprenorphine (M80) are two recently developed opioid antagonists that were chosen based upon their ability to act more selectively than naloxone at kappa and delta (delta) opioid receptor types, respectively. Prior research has demonstrated that when dissolved in acid and administered centrally, MR2266 (20 micrograms) fails to suppress S/G intake. Because all three antagonists are rather insoluble in water, they were dissolved in dimethyl sulfoxide (DMSO). Rats with chronic ventricular cannula were allowed to consume S/G for a 0.5 hr bout. They received a single intracerebroventricular (ICV) injection of antagonist (MR2266: 0, 10, 20 and 40 micrograms; M80: 0, 5, 10, 20 and 40 micrograms or N-BNI: 0, 1, 3, and 10 micrograms) 10 min prior to the start of the drinking bout. Administration of DMSO alone failed to alter drinking relative to saline, whereas each antagonist significantly attenuated S/G intake. We conclude that, when dissolved in DMSO, these antagonists suppress drinking by blockade of opioid receptors. PMID- 2315373 TI - Behavioral effects of early postnatal lead exposure in herring gull (Larus argentatus) chicks. AB - Lead exposure early in life affects behavioral and intellectual development in humans. In this paper, I use the herring gull, Larus argentatus, as an animal model to examine effects of lead exposure on early development. Like humans, birds rely mainly on visual and vocal, rather than olfactory, modes of communication. Each of 24 one-day-old herring gull chicks was randomly assigned to one of three treatment groups to receive a lead nitrate solution at a concentration of 0.0, 0.1 and 0.2 mg/g. The control dose was an equal volume of sterile saline. The trios were not siblings, but were matched by weight. Behavioral tests were performed either daily, every two to five days, or at the end of the experiment (45 days posthatching), depending on the nature of the experiment. The behavioral tests examined locomotion, balance, righting response, begging, recognition, thermoregulation and visual cliff. Although on most days, begging behavior, balance and righting response did not differ significantly, over the 45 days of the experiment control birds performed better on more days than the lead-injected birds. Balance was disturbed by lead-injection for the first six days following injection. Individual recognition developed by day 5 in control birds, by day 10 for 0.1 Pb mg/g birds, and by day 14 for 0.2 Pb mg/g birds. Depth perception and thermoregulation behavior were also adversely affected by lead. PMID- 2315374 TI - Conditioned aversion after delay place conditioning with amphetamine. AB - Male, Sprague-Dawley rats received subcutaneous injections of either dextroamphetamine sulfate (AMP; 3.0 mg/kg) or vehicle [VEH (phosphate buffer); 1 ml/kg] immediately before (standard conditioning) or after (delay conditioning) conditioning sessions in a place-conditioning paradigm. AMP was paired for 4 conditioning sessions with one compartment of a three-compartment place conditioning apparatus; VEH was paired for 4 conditioning sessions with another compartment. Animals were then tested for place preference or aversion by determining the proportion of time spent in each compartment during a 15-minute test session. Standard conditioning with AMP produced a place preference while delay conditioning produced a place aversion. Similar findings had earlier been reported from studies involving conditioned place-preferences and aversions with nicotine. These studies demonstrated that the time of drug administration can be as strong a determinant of place-conditioning effects as the drug itself. PMID- 2315375 TI - Prenatal phencyclidine in rats: effects on apomorphine-induced climbing. AB - Either 5 or 10 mg/kg of phencyclidine (PCP) in saline was administered by subcutaneous injection to gravid dams during the last two weeks of gestation. A pair-fed control group was administered the vehicle alone and allowed to eat and drink only the amount consumed by the 10 mg/kg group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Among the dams receiving 10 mg/kg of PCP, food and water intake was initially reduced to 33-43% of nontreated controls, but then returned to control levels. Surprisingly, after 3 days of drug administration, water intake of PCP-treated dams exceeded that of the nontreated dams by approximately 15%. Compared with the nontreated dams, both PCP groups and pair-fed control dams gained significantly less body weight from conception to term. PCP had no significant effect on number of implantation sites or number of live births, however, PCP produced an apparent selective embryolethal effect on males and body weight reduction in all groups at birth. Prenatal PCP did not alter the sensitivity to apomorphine-induced climbing behavior during the second postnatal week. These results are discussed with respect to published animal and clinical studies of PCP exposure during pregnancy. PMID- 2315376 TI - Prevalence of psychotropic medication in childhood and adolescence in the Federal Republic of Germany. AB - The use of psychotropic drugs in childhood and adolescence has been the subject of intense debate during the last few years. Allegations about the excessive consumption and overprescription of these substances in younger age groups play an important role in the public discussion. In this situation it would be useful to present relevant data on the prescription volume of psychotropic drugs in childhood and adolescence. The present investigation comprises data of 1985 using the GKV drug index and the IMS prescription index. According to the authors' results the prescription volume of these drugs is significantly lower than estimated in previous pilot studies. Illustrating the prescriptions by means of a drug profile, type and prevalence of psychotropic medication in children and adolescents are clearly distinguished from those of other age groups by the greater use of homeopathics and phytopharmaceutics. Among the psychotropics the neuroleptics represent the largest group. In comparison with international drug prevalence studies the prescription volume of psychostimulants is extremely low in the Federal Republic of Germany. PMID- 2315377 TI - Effect of imipramine on liver function tests. PMID- 2315378 TI - Theoretical investigation of estimation of steady and pulsatile blood flow and blood vessel cross section by CW NMR excitation. AB - In this paper we show theoretically that when a magnetised blood bolus enters a CW NMR excitor coil of length Le at resonance and the signal from the T2 decaying, processing transverse magnetisation of the flowing blood spins is subsequently detected by a detector coil of length L separated from the excitor coil by a distance delta l, then by recording CW NMR signals at three positions such as delta l = 0, 0.5 and 1.0 cm one can eliminate the static tissue signal and measure non-invasively the steady component V0 as well as the total vessel cross section, beta accurately. The time dependent part of the CW NMR signal which depends on Vpulse(t), is also dependent on V0 non-linearly unless both L and Le are greater than 50 cm and delta l is zero. Finally, methods of obtaining true Vpulse(t) from the CW NMR signal after applying proper correction due to the steady flow are discussed. PMID- 2315379 TI - Characterisation of mammographic parenchymal pattern by fractal dimension. AB - A consistent, quantitative, observer-independent method of characterising mammographic parenchymal pattern is described. The method is based on the calculation of the 'fractal dimension' of digitised mammograms. The degree of correlation between the parenchymal pattern classifications by a fractal-based system and those of radiologists is assessed. For a set of 70 mammograms, average weighted proportion agreement among three radiologists in calling Wolfe grades was 85%, while agreement between the radiologists and our fractal classifier was 84%. The method developed may prove to be useful in establishing an index of risk for breast cancer and, ultimately, in determining intervals between examinations for individuals in a mammographic screening programme. PMID- 2315380 TI - Feasibility of simultaneous and sequentially administered dual tracer protocols for measurement of regional cerebral haematocrit using positron emission tomography. PMID- 2315381 TI - Photoelectron bremsstrahlung--analytical possibilities. PMID- 2315382 TI - A contact x-ray therapy unit for intracavitary irradiation. PMID- 2315383 TI - What's in a name? PMID- 2315384 TI - Influence of high voltage pulsed direct current on edema formation following impact injury. AB - Edema results in pain and may lead to reduced functional mobility. High voltage pulsed direct current (HVPC) has recently been advocated for edema control. The purpose of our study was to determine the effect of HVPC on edema formation in frogs. Hind limbs of 20 anesthetized frogs were injured by dropping a 450-g weight onto the plantar aspects of the feet. One hind limb of each frog was randomly selected to receive continuous 120-Hz HVPC at voltages 10% lower than those needed to evoke muscle contraction. Four 30-minute treatments were administered at 1.5-hour intervals beginning 10 minutes after trauma. Limb volumes were measured by water displacement. An analysis of variance for repeated measures and a Newman-Keuls post hoc test were used to determine the significance of treatment effects. The HVPC significantly (p less than .01) reduced edema formation. We hypothesize that HVPC may also be effective in controlling edema formation after impact injuries in humans. [Bettany JA, Fish DR, Mendel FC: Influence of high voltage pulsed direct current on edema formation following impact injury. PMID- 2315385 TI - Reliability and validity of judgments of the integrity of the anterior cruciate ligament of the knee using the Lachman's test. AB - This study assessed the intratester and intertester reliability and the validity of judgments of the integrity of the anterior cruciate ligament (ACL) based on the use of the Lachman's test. End-feel and tibial translation judgments made during the Lachman's test were also assessed. Patients with unilateral knee problems (N = 32), 13 of whom had documented ACL damage, were examined by two physical therapists and two orthopedic surgeons. Intratester Kappa values for whether the test was positive or negative were .44 for physical therapists, .60 for orthopedic surgeons, and .51 for all examiners. Intertester Kappa values were .69 for the therapists, .61 for the surgeons, and .42 for all examiners. The predictive value of a positive test was 47% for all examiners, whereas the predictive value of a negative test was 70%. Results indicate that Lachman's test judgments have limited reliability and may be more useful for predicting that a patient does not have an ACL injury than for predicting that the ACL is injured. [Cooperman JM, Riddle, DL, Rothstein JM: Reliability and validity of judgments of the integrity of the anterior cruciate ligament of the knee using the Lachman's test. PMID- 2315386 TI - Postural control in standing following stroke: test-retest reliability of some quantitative clinical tests. AB - Despite their importance to stroke rehabilitation, appropriate clinical tests of postural control in standing appear to be inadequately developed. Several quantitative clinical tests, therefore, were constructed. These tests were used to measure functionally relevant aspects of postural control in standing in 24 stroke patients within a mean time interval of two months following a cerebrovascular accident. Subjects were tested in two stance positions (step and parallel) for five tasks that assessed their ability to withstand perturbations produced by self-generated body movements during functional activities. Intrasession reliability coefficients were very high (r = .94-.99). Intersession reliability coefficients were also high (r = .85-.94). Because the test battery requires minimal training and equipment, it can be easily applied in the clinical setting. The high reliability obtained justifies further evaluation of these tests, which appear to be very promising for use in stroke rehabilitation. PMID- 2315387 TI - Reliability of isokinetic measurements of hip muscle torque in young boys. AB - The purpose of this study was to determine the reliability of measurements of hip muscle torque obtained with the Cybex II isokinetic dynamometer from healthy young boys. Twenty-nine healthy boys, aged 6 to 10 years, were tested two times at one- to two-week intervals. Torque of the hip flexors and extensors and the hip abductors and adductors was assessed at angular velocities of 30 degrees and 90 degrees/sec. The torque generated by each muscle group at 30 degrees/sec was similar to the torque generated at 90 degrees/sec. Intraclass correlation coefficients (ICCs) were used to determine test-retest reliability for measurements of each of the muscle groups at both angular velocities. The ICCs were higher for hip flexion and extension than they were for hip abduction and adduction. The highest ICC (ICC = .84) was found for hip extension at 90 degrees/sec. The ICCs for hip abduction and adduction at both angular velocities were less than .60. Factors that possibly contributed to the relatively low reliability in hip abduction and adduction are discussed. PMID- 2315388 TI - References corrected. PMID- 2315389 TI - Fetal wound healing: a biochemical study of scarless healing. AB - Human fetal surgery is being successfully performed today in a small number of highly selected patients for conditions that may lead to irreversible damage to the fetus and threaten the viability of the newborn. Following surgical repair, fetal wounds heal without scarring. This study was initiated to characterize fetal wounds both histologically and biochemically. Gore-Tex tubing was implanted into the subcutaneous tissue of the back of fetal, newborn, and adult New Zealand white rabbits. Light microscopic examination of healed wounds revealed no evidence of scar formation. Electron microscopy demonstrated a striated fibrillar structure suggestive of collagen within the lumen of the Gore-Tex tubing implants. Amino acid analysis (sensitivity 40 pmol) confirmed the presence of hydroxylysine and hydroxyproline within the Gore-Tex wound chambers indicating the presence of collagen in fetal wounds. The small amount of collagen precluded the typing of the collagen using cyanogen bromide peptide analysis. The absence of scarring and the small amounts of detectable collagen suggest a high degree of reorganization of the connective tissues involved in repair. The fetal wound matrix is rich in hyaluronic acid. Topical hyaluronic acid has been associated experimentally with a reduced amount of scarring in postnatal wound healing. Hyaluronic acid extracted from human skin and scar tissue is associated with collagen and other proteins. We propose that a hyaluronic acid-collagen-protein complex may play a role in fetal wound healing. PMID- 2315390 TI - Craniofacial and oral manifestations of fetal alcohol syndrome. AB - Six representative patients with fetal alcohol syndrome (FAS) were studied for craniofacial and oral anomalies, dental development, and long-term bodily growth patterns. The craniofacial features observed were reduction of total head size, increased head-body ratio, the existence of upper and middle craniofacial asymmetry and telecanthus in some instances, and the features of a long face syndrome with a large gonial angle. Dental development was mildly to moderately delayed, and enamel anomalies were present. Analysis of growth patterns demonstrated compensatory growth in stature, weight, or head circumference and a delayed bone age in some instances. It is suggested that the semiquantitative score system for fetal alcohol syndrome study may fail to diagnose individual cases and that craniofacial features are more important in diagnosis than seems to have been appreciated in the past. PMID- 2315391 TI - Total and subtotal glossectomy: function after microvascular reconstruction. AB - Twelve patients with advanced carcinoma of the floor of the mouth and tongue were treated with total (five patients) or subtotal (seven patients) glossectomy, partial mandibulectomy, and immediate reconstruction with the microvascular composite groin flap. The osteomusculocutaneous groin flap was used in eleven patients, and the osteomuscular flap was used in one patient. The groin musculocutaneous or muscle flap was designed to resemble the shape of the tongue for dynamic food transport, improved swallowing, and acceptable speech. Eight of the 12 patients who survived more than 1 year were evaluated for speech and swallowing. Eight patients were able to speak intelligibly, six patients could tolerate a soft/pureed diet, and two patients were limited to fluids. Cinefluorographic swallow studies using semisolid contrast material showed voluntary active intraoral transport and propulsive pharyngeal emptying without aspiration in six patients with complete flap to palate contact; the remaining two patients were unable to move the intraoral contrast material effectively for swallowing because of poor palatal contact. PMID- 2315392 TI - Nasal surgery complications. AB - This study examines the incidence of serious complications in nasal surgery and discusses the diagnosis and management of these complications. The authors review 259 consecutive cases performed between January 1, 1983, and August 31, 1988. One hundred and ninety-five patients had septorhinoplasties, 29 had septoplasties, and 35 had rhinoplasties. Thirteen of these cases involved serious complications as follows: hemorrhage (5), perforation (4), infections (3), and pneumocephalus (1). All the patients with these serious complications had associated septal and/or turbinate surgery. The diagnosis and management of these complications will be discussed. In this small series of nasal surgery patients, the incidence of serious complications was 5.0 percent, with no fatalities reported. The higher incidence of serious complications occurred when associated septal and/or turbinate surgery was required. Awareness of these complications is essential because of the increasing number of patients presenting to plastic surgeons for nasal surgery in whom associated septal and/or turbinate surgery is necessary. PMID- 2315393 TI - Measurement and study of the nose and face and their correlations in the young adult of Han nationality. AB - The measurement of 13 items in the face and nose of 220 young adults (110 males and 110 females) of the Han nationality between the ages of 18 and 21 years has been done in the Henan Province of China. The means and standard deviations have been obtained, and the significant differences in many items between males and females have been proved. Some items influencing outer nasal shape have been analyzed. The correlations between nose height, nose length, and morphologic facial height and physiognomic facial height have been discussed. The ratio and amount of nasal breadth to facial breadth and nasal breadth to interocular breadth have been compared and analyzed, and the differences among the different races and between the sexes have been explained. PMID- 2315394 TI - Depth of the facial nerve in face lift dissections. AB - Facial nerve depth was measured in 12 cadaver face halves after bilateral face lift dissections. The main nerve trunk emerged anterior to the midearlobe and was 20.1 +/- 3.1 mm deep. Nerve exit from the parotid edge also was deep, averaging 9.1 +/- 2.8 mm for temporal, 9.2 +/- 2.2 mm for zygomatic, 9.6 +/- 2.0 mm for buccal, and 10.6 +/- 2.7 mm for mandibular branches. Distal to the parotid gland, danger areas where nerve branches became superficial were distal temporal, lower buccal, and upper mandibular branches over the masseter muscle and marginal mandibular as it crossed the facial artery. Some protection in these danger areas was provided by fascia, especially superficial temporal and masseteric, while platysma provided some protection for the mandibular branch. Fascial and muscle protection was less in thin cadavers. Face lift dissection can be rapid in areas where facial nerve branches are deep or absent, such as postauricular, inferior to the zygomatic prominence, and near the earlobe. PMID- 2315395 TI - Age-related changes in skin blood flow at four anatomic sites of the body in males studied by xenon-133. AB - The normal skin blood flow in healthy subjects consisting of 28 males whose ages ranged from 20 to 72 years was measured by the xenon-133 clearance method at four different sites of the body to determine the presence of any age-related changes. The following results were obtained: Significant age-related changes were observed in the skin blood flow of the deltoid region, anterior chest, dorsum of the hand, and dorsum of the foot. Normal skin blood flow was demonstrated to be highly dependent on age and to significantly decrease with age. Average skin blood flow at these four regions of those 70 years of age decreased by 30 to 40 percent when compared to that of those 20 years of age. The skin blood flow at the deltoid region of healthy subjects was higher by 6.3 ml/100 gm per minute than that of patients in poor condition with cancer of the head and neck. PMID- 2315396 TI - Long-term results after microlymphaticovenous anastomoses for the treatment of obstructive lymphedema. AB - Over the last 14 years, 134 patients with obstructive lymphedema have been treated with microlymphaticovenous anastomoses. Ninety patients were available for long-term follow-up study. Of these, 52 patients were treated by microlymphatic surgery only and 38 of them also had segmental or radical reduction surgery, either at the same time or secondarily. Objective assessment was undertaken by volume and circumferential measurements. Initially, lymphangiography was used, but a study demonstrated increased edema immediately following the investigation in one-third of the patients and it was abandoned, both preoperatively and postoperatively. In the microlymphaticovenous anastomoses only group (N = 52), subjective improvement occurred in 38 patients (73 percent). Objectively, volume changes showed a significant improvement in 22 patients (42 percent), with an average reduction of 44 percent of the excess volume. In the microlymphaticovenous anastomoses and reduction surgery, usually segmental, group (N = 38), subjective improvement occurred in 30 patients (78 percent) and objective improvement occurred in 23 patients (60 percent), with an average reduction of 44 percent of the excess volume. Of those followed up, 67 patients (74 percent) have been able to discontinue the use of conservative measures, with an average follow-up of 4.0 years and average reduction in excess volume of 26 percent. There was a 58 percent reduction in the incidence of cellulitis following surgery. In those patients who were improved, drainage resulted in increased softness of the limbs. Edema of the hand diminished considerably in most patients, although this was difficult to measure. These long-term results indicate that microlymphaticovenous anastomoses have a valuable place in the treatment of obstructive lymphedema and should be the treatment of choice in these patients. Reduction surgery can be used as an adjunct in some of these patients, especially in the posteromedial aspect of the upper arm. Liposuction has been used in failed cases or in patients in whom no lymphatics could be found. Improved results can be expected with earlier operations because patients referred earlier usually have less lymphatic disruption. PMID- 2315397 TI - An experimental model for chronic lymphedema. AB - Although a multitude of operations exist for the treatment of lymphedema, none is highly successful. An experimental model that reliably and easily produces chronic lymphedema in an extremity would be useful to study treatments in a controlled and comparative manner and would enhance our understanding of the physiology and treatment of lymphedema. Many models that simulate clinical lymphedema have been described, but they suffer from cumbersome protocols, high laboratory costs, and an inconsistent yield of permanent lymphedema. We describe an experimental model for chronic lymphedema in the lower extremity of the rat that creates a lymphatic block in the groin induced by radiation treatment and one operation--surgical division of the superficial and deep lymphatics. All animals develop stable chronic lymphedema of the lower extremity within days of operation, with swelling that persists for at least 9 months. A mortality rate of 8 percent was associated with this technique. Methods for quantification of limb swelling are described, as is analysis of the lymphatic block by lymphoscintigraphic imaging of lymph channels and nodes. This model has the advantages of simplicity of technique, cost-effective use of rodent subjects, reproducibility of lymphedema, and quantification of results. PMID- 2315398 TI - Vascularized periosteum associated with cancellous bone graft: an experimental study. AB - The association of a vascularized periosteal flap with a cancellous bone graft was studied on a group of 20 Wistar rats. Ten rats were sacrificed at 6 weeks and seven at 12 weeks (three died prematurely). The behavior of the cancellous bone graft buried in striated muscle and the osteogenic capacity of a simple vascularized periosteal flap also were observed on the same animals. Results of the study are as follows: In 14 of 17 animals, a vascularized periosteal flap wrapped around a cancellous bone graft resulted in new cortical bone formation with little resorption of the initial cancellous graft. A vascularized musculoperiosteal flap has produced a small amount of new compact bone only in 4 of 17 animals. A cancellous bone graft buried into well-vascularized muscle tissue was resorbed (15 cases) or necrotic (2 cases) at 12 weeks. In conclusion, the association of a vascularized periosteal flap and cancellous bone is a better means to produce compact bone than a vascularized periosteal flap alone or an isolated cancellous bone graft. PMID- 2315399 TI - Update on the anatomy of the pulley system in the chicken foot long digit. AB - The pulley system in the flexor sheath of the long toe of the white leghorn chicken foot was studied. Histologic sections of the pulleys were prepared, and the mechanics of flexion of the long toe was analyzed. An annular flexor pulley that attached to the third phalanx was identified. This pulley, which has not been described previously, was found to be essential for proper flexion of the third interphalangeal joint. PMID- 2315400 TI - Cranial fasciitis of childhood. AB - Cranial fasciitis of childhood is a benign lesion occurring superficial to or involving the cranial bones of children at a median age of 18 months, with a male sex predilection of 2:1. It is histologically described as a well-circumscribed, loose proliferation of stellate to spindle-shaped fibroblasts in a myxoid background with foci of hemorrhage and hyalinization. Mitotic figures, increased cellularity, and cellular immaturity may be seen. The treatment of choice is excisional biopsy, since the lesion is not known to recur. It is important that the pathologist and surgeon alike be able to differentiate this benign condition from other lesions because of the clinically threatening presentation of cranial fasciitis. PMID- 2315401 TI - Island scalp flap for superior forehead reconstruction. AB - An island scalp fasciocutaneous flap, based on the posterior superficial temporal vessels, is described for single-stage reconstruction of full-thickness forehead and scalp defects. The hairline can be precisely determined and tailored to restore symmetry. By removing the hair-bearing dermis of the forehead portion of the flap and placing a full-thickness skin graft, aesthetic reconstitution of the forehead skin is achieved. This flap is especially useful when exposed calvarium limits other techniques. PMID- 2315402 TI - Functional support for flap reconstruction of the lower lip and mandible. AB - A case of functional support for distant flap reconstruction of the entire lower lip and mandibular symphysis following resection of an aggressive recurrent basal cell carcinoma of the lip is presented. Resection of the entire lower lip and mandibular symphysis includes loss of the orbicularis oris and attached muscles of the modiolus as well as the buccinator and masseter muscles. Without the support of these muscles, control of saliva as well as solid and liquid food is lost and articulation is hampered. In this case, fasciae latae strips attached to distally transected temporalis muscle tendons were tunneled bilaterally into the lower lip and chin area, which had been previously reconstructed with deltopectoral and pectoralis major musculocutaneous flaps. PMID- 2315403 TI - Technique for correction of lop ear. AB - Various techniques of correction of lop ear have been described. Minor lop ear deformity can easily be corrected with simple excision of the overhanging auricular cartilage. Moderate and severe lop ear deformities, on the other hand, are more difficult to correct because there is actual reduction in size of the upper third of the ear in addition to the overhanging auricular cartilage. The purpose of this paper was to present a new technique used to correct the moderate lop ear deformity. In addition to excising the overhanging cartilage, I rotate a cartilage flap from the anthelix upward where the missing superior crus was supposed to be. This flap increases the vertical height of the ear and creates a new superior crus. I applied this technique on three cases of moderate lop ear deformities with good results. PMID- 2315404 TI - The employment of suction for the removal of siliconomas. PMID- 2315405 TI - Transparent luminescent illuminator. PMID- 2315406 TI - Staphylococcus aureus inflammation and cleft palate in mice. PMID- 2315407 TI - Complications of autografting fat obtained by liposuction. PMID- 2315408 TI - Determining the area of a lesion or a flap. PMID- 2315409 TI - Internal fixation of malar fractures. PMID- 2315410 TI - Peripheral in-continuity tissue examination. PMID- 2315411 TI - Mohs' micrographic surgery versus peripheral in-continuity tissue examination. PMID- 2315412 TI - To be or not to be an island fasciocutaneous flap. PMID- 2315413 TI - Prevention of burr hole defects. PMID- 2315414 TI - Galactorrhea after reduction mammaplasty. PMID- 2315415 TI - Cultured epithelial autografts for giant congenital nevi. PMID- 2315416 TI - The dog-ear in areolar reconstruction. PMID- 2315417 TI - Fixation of suction drains. PMID- 2315418 TI - A 90-degree twisted scalpel. PMID- 2315419 TI - [Panic attacks and avoidance behavior]. AB - In a crossectional investigation based on a group of 122 patients with panic attacks, compiled from a variety of hospitals and therapy institutions, 97 patients were found to be suffering from panic disorder as a relevant medical problem. The disease, however, is often identified in an unsatisfactory manner. Avoidance behaviour (extensive or limited) associated with a severe form of panic disorder, was evident in more than one-half of the group (60%). In these patients the incidence of panic attacks is higher, anxiety is more marked, and there are more often additional anxiety disorders (generalised anxiety, sociophobia). These results underline the importance of early recognition and specific treatment of panic disorder to prevent development of avoidance behaviour. PMID- 2315420 TI - Neuropsychological deficit in schizophrenic subtypes: paranoid, nonparanoid, and schizoaffective subgroups. AB - Schizophrenic patients were carefully diagnosed and screened for a history of neurological disorders. Diagnosis and subtyping was based on DSM-III-R criteria, using the Structured Clinical Interview for DSM-III-R, which was administered by trained interviewers and confirmed by a research psychiatrist. The schizophrenic patients were compared with an age-matched control group on an extensive battery of neuropsychological measures. The undifferentiated/disorganized schizophrenic patients were consistently the most impaired on a broad range of tasks. When the effect of symptom severity and drug level were statistically controlled (analysis of covariance), however, the magnitude and number of differences were substantially reduced. The perseverative error score from the Wisconsin Card Sort Test showed the greatest difference between the groups. However, the strongest and most consistent effects were observed in relation to symptom ratings. These data indicate the importance of controlling for medication and symptom severity, and suggest that current diagnostic classifications may not be the most useful factors for studies of the cognitive correlates of schizophrenia. PMID- 2315421 TI - Anhedonia and the deficit syndrome of schizophrenia. AB - Schizophrenic outpatients with and without the deficit syndrome were administered Chapman's "psychosis proneness" scales. As hypothesized, deficit syndrome patients had higher scores on Social Anhedonia and Physical Anhedonia, but did not differ from nondeficit patients on Perceptual Aberration, Magical Ideation, or Impulsive Nonconformity. The differences between the two groups were not related to race, gender, age, socioeconomic status of family of origin, or drug treatment. These results support the validity of the deficit syndrome, and suggest that the Social Anhedonia and Physical Anhedonia scales may be useful in future studies of schizophrenia. PMID- 2315422 TI - Neuroendocrine aspects of primary endogenous depression: IX. Receiver operating characteristic analysis of the dexamethasone suppression index vs. the dexamethasone suppression test in patients and controls. AB - The dexamethasone suppression index (DSI), which is the product of the postdexamethasone (DEX) serum DEX concentration and the post-DEX serum cortisol concentration, has been suggested to be a more sensitive discriminative test for depression than the standard DEX suppression test (DST). We used receiver operating characteristic (ROC) analysis to examine the DSI, calculated in several ways, versus the standard DST in a sample of 40 endogenous major depressives and 40 matched normal control subjects. The ROC analysis indicated that the DSI offers no advantage over the standard DST, regardless of which criterion values are used to define cortisol nonsuppression. Serum DEX determinations appear to have value primarily as an indicator of the minimum DEX concentration necessary for an accurate DST. PMID- 2315423 TI - Using the CES-D scale to screen for depression and anxiety: effects of language and ethnic status. AB - The purpose of this report is to present data on the effects of language (English/Spanish) and ethnic status (white/non-Hispanic or Mexican origin) on the ability of the Center for Epidemiologic Studies Depression (CES-D) scale to detect cases of clinical depression and generalized anxiety identified using the Diagnostic Interview Schedule (DIS) in psychiatric treatment settings. The agreement between the CES-D scale and the DIS diagnoses of major depressive disorder (MDD) and generalized anxiety disorder (GAD) was poor, especially among Mexican-origin patients interviewed in Spanish. Multiple regression analysis revealed that the CES-D scale was positively associated with MDD in all groups. In addition, GAD also was associated with the CES-D scale in Anglos and English speaking Mexican-Americans but not in Spanish-speaking Mexican-Americans. PMID- 2315424 TI - Evoked potential augmenting-reducing in psychopaths and criminals with impaired smooth-pursuit eye movements. AB - Previous studies that have assessed a stimulation-seeking theory of psychopathy are open to the criticism that psychopaths may lie on self-report questionnaires. The present study uses event-related potential (ERP) augmenting-reducing as a psychophysiological analog of stimulation-seeking in psychopaths to test this theory. It is also hypothesized that "schizoid" criminals, as defined by poor eye tracking, would show nonaugmenting/reducing, a profile characteristic of schizophrenia. Schizoid criminals were found to be characterized by nonaugmenting/reducing, but psychopaths were not found to be characterized by augmenting. It is concluded that stimulation-seeking is a viable theory of criminality but not of psychopathy, and that the etiological basis to schizoid criminality may differ substantially from criminality, per se. PMID- 2315425 TI - Statistical issues in the identification of risk factors for suicidal behavior: the application of survival analysis. AB - Studies of suicide risk factors generally examine suicidal behavior as a dichotomous outcome. Survival analytic techniques are discussed in which the time until a suicide attempt from a specific point, such as prior attempt or onset of illness, is also examined. These procedures can incorporate information on those lost to followup or "censored." One survival analytic technique, Cox's proportional hazards model, is a particularly informative statistical technique for the study of suicidal risk factors because several covariates can be incorporated. Illustrative analyses estimate the significance of different risk factors, and demonstrate that there is a 32% increase in the relative risk of a suicide attempt associated with each prior attempt. PMID- 2315426 TI - Intravenous cocaine self-administration in rats is reduced by dietary L tryptophan. AB - Rats were trained to self-administer intravenously-delivered cocaine. Four lever press responses resulted in a cocaine infusion (0.2 mg/kg) during daily 24-h sessions. The rats were also trained to obtain water from tongue-operated solenoid-driven drinking spouts. Ground food and water from a standard drinking bottle were also available. When cocaine injections reached stable levels, L tryptophan was mixed with the rats' food for 5 days. Three concentrations of L tryptophan (2, 4, and 8%) were tested in different groups of five rats each. Three other groups of five rats each received the same L-tryptophan treatments; however, in these rats saline was substituted for cocaine and a sweet drinking solution consisting of glucose and saccharin (G + S) replaced water in the automatic drinking device. Two other groups consisting of five rats each self administered a higher (0.4 mg/kg) or lower (0.1 mg/kg) unit dose of cocaine and food adulterated with 4% tryptophan. At the two higher concentrations L tryptophan reduced cocaine infusions by at least 50% during the 5 days of treatment, and cocaine infusions returned to baseline levels within 48 h after the regular diet was restored. Responding reinforced by the G + S solution was not altered by any of the L-tryptophan concentrations. Food intake was substantially lowered by the 8% L-tryptophan concentration; however, water intake, responding on an inactive lever, and the number of saline infusions were not affected by addition of L-tryptophan to the food. L-Tryptophan had the same magnitude of effect on self-administration of the 0.1 and 0.2 mg/kg unit doses of cocaine, but behavior maintained by the highest cocaine dose (0.4 mg/kg) was resistant to the effect of L-tryptophan. The results of this experiment indicate that L-tryptophan reduces behavior reinforced by IV cocaine infusions. PMID- 2315427 TI - Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats. AB - Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2-32 mg/kg IP) as well as idebenone (10-100 mg/kg IP) and physostigmine (0.1-0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems. PMID- 2315428 TI - Reduced behavioral variability in extinction: effects of chronic treatment with the benzodiazepine, diazepam or with ethanol. AB - Extinction of a food reinforced habit results in an increase in the variability of the response learned in acquisition and in the appearance of previously suppressed competing responses. The purpose of the present study was to examine the effects of chronically administered diazepam (0.0, 1.5, 3.0, or 6.0 mg/kg, IP, -30 min) or 10% ethanol (0.0, 1.0, 1.5, or 2.0 g/kg, IP, -15 min) on such behavioral variability in the extinction of radial maze performance. Eight groups of food deprived rats (n = 6) were given one of the forementioned doses for 2 sessions of baseline, 18 sessions of acquisition, and 5 sessions of extinction. In acquisition, eight rewards of two food pellets were obtained on each of three trials in each session. The food well at the end of each arm was rebaited when emptied by the animal, consequently an entry into any arm was reinforced. In baseline and extinction no food was available in the maze. Each session consisted of three 10-min trials. In extinction, compared to treatment with vehicle, both diazepam and ethanol treatments decreased the rate of the instrumental response, arm entry, and increased the variability of the instrumental response and of competing responses. Only the effects of the drugs on the competing responses in extinction were greater than those observed in acquisition. It was concluded that the interference-reduction model of drug action best described the magnitude of the drug effects and the variability-reduction model best predicted the direction of the effects. PMID- 2315429 TI - Subjective and behavioral effects of marijuana the morning after smoking. AB - Twelve regular marijuana smokers participated in a study designed to detect possible after-effects associated with marijuana smoking. Each subject was evaluated for two weekends-during one weekend they received only placebo marijuana (0.0% THC); the other weekend they received active marijuana (2.1% THC). Each weekend subjects received a total of 40 standardized puffs of marijuana smoke, administered during five separate smoking periods in the late afternoons and evenings. Each morning after smoking, subjects completed a series of questionnaires evaluating their sleep and mood, and then performed a battery of tasks to assess their psychomotor and cognitive function. Ratings of "high" and heart rate indicated that effective doses of THC were delivered to the subjects, and expired air carbon monoxide levels demonstrated effective smoke administration over the course of the weekends. No evidence of residual subjective intoxication was found, and most of the behavioral tasks and mood scales were unaffected the morning after. Statistically significant after-effects were obtained on a few measures, but with one exception, these were of negligible magnitude, inconsistent with previous findings, or likely artifacts of the experimental situation. In short, marijuana smoking was not associated with a "hangover" syndrome similar to those reported after use of alcohol or long-acting sedative-hypnotics. PMID- 2315430 TI - Aspects of amitriptyline and nortriptyline plasma levels monitoring in depression. AB - Fifty-nine depressed female inpatients were treated with 100 mg amitriptyline (AMT) IM for 4 weeks. Depression ratings and determinations of the parent drug and nortriptyline (NT) were performed weekly. No direct relationship between plasma AMT + NT concentrations and therapeutic response was apparent, but beneficial therapeutic responses and significantly lower side-effect scores were more frequently noted in subjects with concentrations in the 100-200 ng/ml range. AMT + NT concentrations were significantly correlated with age. No significant difference was found in the number of responders between younger and older subjects with two clinical improvement criteria; however, a significant difference emerged when a third more restrictive clinical outcome criterion was adopted. The implications of the present findings for patient treatment and for the interpretation of previous studies are discussed. The data collected point to a possible usefulness of monitoring AMT and NT plasma levels, even if further investigations are needed. PMID- 2315431 TI - Effect on radiolabelled-monoamine uptake in vitro of plasma taken from healthy volunteers administered the antidepressant sibutramine HCl. AB - Sibutramine HCl, a monoamine reuptake inhibitor type of antidepressant, was administered to healthy male volunteers as either a single dose (12.5 or 50 mg) or repeated treatment (5-20 mg once daily or 15 mg twice daily). Plasma, obtained at regular intervals during and after sibutramine HCl or placebo treatment, was assayed in vitro for its ability to inhibit the uptake of [3H]-noradrenaline (NA) by rat cortical synaptosomes, [3H]-5-hydroxytryptamine (5HT) by human platelets and [14C]-dopamine (DA) by rat striatal synaptosomes. After both single and repeated sibutramine HCl administration, the rank order of uptake inhibition was [3H]-NA greater than [3H]-5HT greater than [14C]-DA. The level of monoamine uptake inhibition increased on daily administration to a plateau 4-6 days after initiation of treatment, for example, approximately 60% and 40% inhibition of [3H]-NA and [3H]-5HT, respectively, following 15 mg sibutramine HCl twice daily. The pattern of monoamine uptake inhibition following sibutramine HCl administration to man is similar to that observed in sibutramine HCl-treated rats, and probably at least partly reflects inhibition of uptake by drug metabolites in both species. The inhibition of monoamine uptake following sibutramine HCl administration to man is consistent with an antidepressant effect. PMID- 2315432 TI - Administration of leu-enkephalin impairs the acquisition of preference for ethanol. AB - The effects of subcutaneous administration of leu-enkephalin (LEU-E) (10, 100 and 300 micrograms/kg) and LEU-E (100 micrograms/kg) plus naloxone (2.5 mg/kg) on ethanol preference and fluid intake have been investigated in rats. Under our procedural conditions, rats develop ethanol preference through forced ethanol drinking (conditioning session). Preconditioning administration of LEU-E induced a reduction of later ethanol preference. Post-conditioning administration of LEU E (10 and 100 micrograms/kg) also attenuated the development of ethanol preference. NX antagonized the effects of LEU-E on ethanol preference and fluid consumption in the two experimental procedures used, indicating an involvement of opioid receptors in the LEU-E-induced impairment of the acquisition of ethanol preference. PMID- 2315433 TI - Bromocriptine self-administration and bromocriptine-reinstatement of cocaine trained and heroin-trained lever pressing in rats. AB - Rats were trained to lever press for intravenous cocaine (1.0 mg/kg/injection) and then switched to bromocriptine (0.3, 1.0, or 3.0 mg/kg/injection) on a FR-1 reinforcement schedule. Bromocriptine sustained responding at all three doses; hourly drug intake increased linearly with log-dose. In a second experiment, animals were trained to respond for cocaine (1.0 mg/kg/injection) or heroin (0.1 mg/kg/injection) reinforcement; drug was available for the first 2 h of each daily session; saline was substituted for cocaine or heroin for 5 subsequent hours. One hour into each saline substitution session, an intravenous injection of saline or bromocriptine (0.0, 0.5, 1.0, or 2.0 mg/kg) was given. Bromocriptine reinstated both cocaine-trained and heroin-trained lever pressing; under these conditions, the drug was most effective in the heroin-trained animals. Reinforcing doses of clonidine (0.0625 and 0.125 mg/kg), methohexital, and nicotine (0.05 and 0.1 mg/kg), and a sub-intoxicating dose of ethanol (2 g/kg) failed to reinstate cocaine-trained responding. These data indicate that bromocriptine has cocaine-like and heroin-like stimulus and reinforcing effects. PMID- 2315434 TI - Effects of smoking context on habituation to a repeated cognitive task. AB - This study assessed the role of smoking-related cues on habituation of electrodermal responding and facial neuromuscular responses in male smokers. In three of the four groups, subjects smoked for the first five trials followed by the laboratory arithmetic task. On the sixth trial one group of subjects continued to smoke nicotine cigarettes, while the context was changed for subjects in the other groups by 1) omitting the pharmacological cues (smoking a non-nicotine cigarette) or 2) omitting both the pharmacological and behavioral cues (not smoking). Subjects in a non-smoking control group did not smoke before any of the six trials. During trials 1-5, smoking significantly increased the rate of habituation of electrodermal activity. On trial 6, electrodermal activity significantly increased for subjects who had a change in smoking context, whether it involved removal of pharmacological or smoking plus pharmacological cues. No differences in electrodermal activity were observed between subjects in these groups compared to non-smoking control subjects. Smoking increased zygomatic activity (predominant during smiling) during trials 1-5, consistent with an interpretation of the positively reinforcing nature of smoking. Corrugator activity (predominant during frowning or concentration) increased for subjects who had both the pharmacological and behavioral smoking cues omitted on trial 6. PMID- 2315435 TI - Ontogeny of the enhanced behavioral response to amphetamine in amphetamine pretreated rats. AB - Repeated administration of amphetamine to adult rats results in enhanced behavioral responses to subsequent amphetamine exposure. These experiments were designed to determine the earliest age at which behavioral sensitization to amphetamine could be detected. Rats from both sexes (n = 6-8/group) at ages of 1, 7, 21 or 49 postnatal days (PNDs) were injected with either d-amphetamine sulfate (5 mg/kg) or saline, SC, twice daily for 5 consecutive days. Stereotyped behavior and locomotor activity responses to a challenge dose of d-amphetamine (2.5 mg/kg), or saline, IP, were assessed for a total of 90 min, 15 days after the last dose of pretreatment. Amphetamine-induced stereotyped behavior was significantly enhanced only when amphetamine pretreatment was initiated at PND 49, but not at the earlier ages of PND 1, 7 or 21. There was no apparent sex difference in this effect. Correspondingly, amphetamine-induced locomotor activity was reduced in both sexes of the same age group (PND 49), but not in groups pretreated earlier, when compared to the saline-pretreated rats. These results suggest that amphetamine sensitization may be a late-developing effect, one which occurs sometime after the 3rd week of postnatal life. PMID- 2315436 TI - Buspirone impairment of performance of passive avoidance and spatial learning tasks in the rat. AB - The effects of buspirone on the execution of step-through passive avoidance and spatial navigation learning tasks were assessed. In view of the anxiolytic properties of the drug, its effects on shock induced ultrasonic vocalizations and shock suppressed locomotor activity in a hole-board were also determined. Doses (0.5, 1 and 2 mg/kg, IP) which did not affect exploratory activity in a novel environment (light/dark box and hole-board apparatus) were used. Buspirone (1 and 2 mg/kg) impaired performance on the 24 h passive avoidance recall test when given prior to the training and the test sessions or prior to the test session only but not when given before the training trial only. The stress response to the mild footshock, as measured in terms of suppressed locomotor activity in the hole-board apparatus and post-shock ultrasonic vocalizations, was reduced by buspirone (at 1 and 2 mg/kg, respectively), indicating that its effect on behavior in the passive avoidance learning task is probably due to its anxiolytic properties. Evidence for a possible amnesic effect of buspirone (2 mg/kg) was found on the acquisition and probe test trials in the spatial navigation task. During training the latency to find a submerged escape platform in a water maze was increased. Performance on a probe test was also impaired but this effect was not apparent in animals which had received buspirone only prior to the probe test. Although these changes may be attributable to alterations in many aspects of cognitive processing, the possibility of a direct effect on memory warrants further investigation. PMID- 2315438 TI - Amphetamine disruption of prepulse inhibition of acoustic startle is reversed by depletion of mesolimbic dopamine. AB - Previous studies have demonstrated that dopamine (DA) agonists disrupt sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats; other reports suggest that this stimulant-induced disruption of PPI may reflect drug-induced increases in ASR amplitude rather than changes in sensorimotor gating. In the current study, 6-hydroxydopamine lesions that depleted dopamine from the nucleus accumbens, olfactory tubercles and anterior striatum reversed the disruption of PPI caused by amphetamine (AMPH), but did not disrupt AMPH potentiation of ASR baseline. These findings strongly suggest that increased mesolimbic DA activity is one substrate of the AMPH induced disruption of PPI; in contrast, AMPH potentiation of baseline startle amplitude may be independent of mesolimbic DA activation. PMID- 2315437 TI - Intermittent and continuous haloperidol regimens produce different types of oral dyskinesias in rats. AB - Rats were administered equivalent doses of haloperidol for either 28 days or 8 months using one of two different drug regimens: intermittent (i.e., weekly injections) or continuously (via drinking water and osmotic mini-pumps). Oral movements were determined by human observers and by a computerized video analysis system, which determined number and amplitude of jaw openings and closings (computer-scored movelets "CSMs") as well as the slope (amplitude/duration) and frequency spectrum (fourier transform) of oral activity. The two drug groups developed distinctively different changes over time. Continuous administration resulted in late-onset oral activity changes at 1-3 Hz and withdrawal increases in CSMs, a pattern expected of tardive dyskinesia. Intermittent treatment produced a primed dystonia-like pattern: large amplitude CSMs which had steep onset slopes and a peak energy at 4-7 Hz. These results demonstrate the importance of drug regimen in determining the type of neuroleptic-induced dyskinesias which develop with prolonged neuroleptic treatment in rodents. PMID- 2315440 TI - Radiation-induced chromosome 2 rearrangement and initiation of murine acute myeloid leukemia. PMID- 2315439 TI - Effects of nalmefene on feeding in humans. Dissociation of hunger and palatability. AB - Effects of nalmefene on eating were investigated in two groups of ten male volunteers, in a double-blind placebo-controlled study. The nalmefene treated group ate 22% less, both in terms of absolute weight and caloric intake, of a standardised buffet-meal than did the placebo group. No differences in subjective ratings of hunger or satiety were found between the groups, suggesting that the reduced feeding was not a consequence of any change in motivation to eat. When analysed by nutrient content, nalmefene was found to reduce fat and protein, but not carbohydrate, intakes. Analyses of intakes of individual foods showed a differential effect of nalmefene on foods rated as highly palatable. Thus the apparent nutrient specificity of nalmefene appeared to be an indirect consequence of its effect on palatability. Nalmefene also caused slight increases in self rated alertness, and decreases in ratings of tiredness and elation, although it was thought unlikely that these accounted for observed changes in eating behaviour. No other side-effects were detected, and performance on a choice reaction time task was unaffected. These results add weight to suggestions that endogenous opioids are involved in reward-related aspects of feeding associated with food palatability. PMID- 2315441 TI - Biological and molecular aspects of radiation carcinogenesis in mouse skin. AB - The process of mouse skin carcinogenesis can be operationally subdivided into at least three stages which have been termed initiation, promotion, and progression. Ionizing radiation has been found to be a weak initiator of malignant squamous cell carcinomas (SCCs) when radiation was followed by repeated treatments of the skin with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Besides SCCs, ionizing radiation was found to induce, independent of tumor promoters, basal cell carcinomas (BCCs), a tumor histology not normally seen with chemical carcinogens and mouse skin. Fractionated doses of 1 MeV electrons were found to enhance the conversion of chemically induced benign papillomas to malignant SCCs. In addition to the biological studies, questions related to dominant transforming genes and differential gene expression in the radiation-initiated mouse skin tumors have been explored. Distinct non-ras dominant transforming gene(s) have been detected in radiation-initiated, TPA-promoted SCCs. Differences in the expression pattern of tumor-associated genes were seen in comparing chemically to radiation-induced benign and malignant skin tumors. Therefore, ionizing radiation has been shown to be active in the initiation of malignant skin tumors and progression of benign to malignant tumors in the mouse skin. The ability to divide the process of carcinogenesis into multiple stages in the mouse skin model has facilitated mechanistic studies that may elucidate the molecular pathways involved in radiation-versus chemically induced tumor development. PMID- 2315442 TI - Interactions between cell populations influence expression of the transformed phenotype in irradiated rat tracheal epithelial cells. AB - A combined in vivo-in vitro model has been utilized to evaluate the influence of cell-cell interactions on expression of radiation-induced transformation in irradiated rat tracheal epithelial cells. Two types of cell interactions are evaluated. One type of interaction appears to involve direct cell-cell contact as occurs within the intact tissue. The other type of communication appears to be mediated via a diffusible factor, most likely transforming growth factor type beta. The data suggest the need to be cautious when extrapolating from transformation data obtained following irradiation of low-density rapidly proliferating cell cultures to the in vivo model. PMID- 2315443 TI - Monte Carlo calculations of free ammonia production in deoxygenated solutions of glycylglycine irradiated by X rays and 60Co gamma rays. AB - Detailed-history Monte Carlo computer codes were used to simulate the formation, diffusion, and chemical reaction of free-radical species within deoxygenated aqueous solutions of glycylglycine irradiated by 250-kVp X rays and by 60Co gamma rays. In one reaction, hydrated electrons react with the glycylglycine solute to produce unbound, or free, ammonia. This reaction is complete by 10(-6) s within individual electron tracks for glycylglycine concentrations greater than or equal to 0.025 M. For solute concentrations from 0.025 to 1.2 M, calculated G values of free ammonia are in excellent agreement with measured values. In addition, the computer model predicts a statistically significant difference between the G value of free ammonia produced under X irradiation and that produced under 60Co gamma irradiation. PMID- 2315444 TI - Measurement of free ammonia produced by X irradiation of glycylglycine in aqueous solution. AB - This research was initiated to test the validity of predictions based on Monte Carlo calculations of the effect of ionizing radiation on a simple dipeptide. The mechanism for the formation of ammonia, proposed by Garrison, Sokol, and Bennett Corniea (Radiat. Res. 53, 376-384, 1973), was reevaluated by measuring the yields under deoxygenated and oxygenated conditions. Although free ammonia was formed under both conditions, the yields were different, depending on the concentrations of solute and molecular oxygen. The reaction probabilities of the specific interactions of free radicals formed in pure water with solute and oxygen are discussed to account for the observed difference. Our results obtained after low dose-rate X irradiation are compared with those obtained by Garrison et al. after high-dose-rate 60Co gamma irradiation. PMID- 2315445 TI - Stage-dependent variation in the radiosensitivity of DNA in developing male germ cells. AB - The induction and rejoining of gamma-ray-induced DNA single-strand breaks (SSBs) were measured in the spermatogenic cells of mice using the alkaline elution technique. The animals were injected with [3H]thymidine and sacrificed on subsequent days to examine selectively cohorts of radiolabeled cells in the successive stages of maturation. A significantly increased frequency of SSB was observed in the unirradiated early spermatocytes and late spermatids, associated with genetic recombination and chromatin compaction, respectively. The frequency of SSBs induced by irradiation of animals in vivo remained constant from the early spermatocyte through mid-spermatid stages and decreased significantly only after the cells matured to the late spermatid stage. The frequency of SSBs after in vitro irradiation of testicular cell suspensions also decreased as round spermatids matured to late spermatids. Such decreases for both modes of irradiation may result from maturation-dependent alterations in chromatin in late spermatids, such as condensation and replacement of histones with protamines, rather than from changes in oxygen tension. Rejoining of SSBs in vivo was efficient in the spermatocytes and early spermatids but declined in late spermatids. Possible reasons for the discrepancy between the greater number of unrepaired lesions and lower susceptibility to mutation induction in late spermatids than in round spermatids are discussed. PMID- 2315446 TI - Time-temperature relationships for L1A2 cells step-down heated from 38 to 45 degrees C in vitro. AB - The in vitro response of L1A2 cells to a single exposure to one temperature and to step-down heating was investigated. Single heating consisted of heating for a specified time at a constant temperature in the range 38.0-45.0 degrees C, whereas step-down heating involved a pretreatment of either 45.0 degrees C for 10 min or 42.0 degrees C for 90 min. The pretreatments were adjusted to give the same survival level. The survival curves for single heating had an initial shoulder followed by an exponential region, whereas for step-down heating they were strictly exponential and had no shoulder. The time-temperature relationship for cells exposed to single heating showed a biphasic Arrhenius curve with a downward inflection at 40.5 degrees C. Biphasic Arrhenius curves were also observed for step-down heating, but both the 45 degrees C/10 min and the 42 degrees C/90 min pretreatment showed an upward inflection that broke at 42.5 degrees C and 40.5 degrees C, respectively. The downward inflection on the Arrhenius curve for single heating has been attributed to thermotolerance development and the effect of step-down heating to a temporary inhibition of thermotolerance development. However, the present shape of the Arrhenius curves for step-down heating cannot be explained by inhibition of thermotolerance. It is therefore reasonable to assume that step-down heating is more than just the inhibition of thermotolerance, and that step-down heating and thermotolerance are distinct phenomena which act independently. PMID- 2315447 TI - Dose-dependent metabolic response of mammary carcinoma to photodynamic therapy. AB - The metabolic response of mammary carcinoma in the C3H mouse to photodynamic therapy (PDT) was measured using in vivo 31P nuclear magnetic resonance (31P-NMR) spectroscopy and pH microelectrodes. Twenty-four hours after administration of Photofrin II (12.5 mg/kg), the tumor was subjected to photoactivation using an argon dye laser. Optical treatment doses were 200, 400, and 600 J/cm2 and corresponded to the following tumor control doses: TCD10/30, TCD50/30, and TCD90/30, respectively. In vivo 31P-NMR spectra and pH micro-electrode measurements were obtained prior to treatment and at 4, 24, 48, and 72 h and 1 week post-treatment. The data revealed a significant (P less than 0.0002) alkalosis as indicated by the pH measured by NMR compared to pH measured by microelectrodes at all treatment levels and time points. Spectral differences between treatment groups were apparent as early as 4 h after treatment. The ratio of beta-nucleoside triphosphate to inorganic phosphate at 4 h after treatment was significantly (P less than 0.01) smaller for 600 J/cm2 treatment than for 200 J/cm2 treatment. At curative (600 J/cm2) levels, from 48 h on, no phosphate resonances were detected in the spectra. The pH measured by NMR transiently decreased from pretreatment levels after 200 and 400 J/cm2 treatment (P less than 0.002, P less than 0.009, respectively), while no change in pH from pretreatment values was found after 600 J/cm2 treatment. The data suggest that the early metabolic response of mammary carcinoma to PDT, as indicated by 31P-NMR spectroscopy, is dose dependent, and may be a sensitive indicator of biological outcome to treatment. PMID- 2315448 TI - Changes in 31P nuclear magnetic resonance with tumor growth in radioresistant and radiosensitive tumors. AB - In vivo 31P nuclear magnetic resonance (31P NMR) spectroscopy has been used to compare metabolic profiles with tumor radiosensitivity. A radioresistant mammary carcinoma (MCa) and a radiosensitive methylcholanthrene-induced fibrosarcoma (Meth-A) were studied by 31P NMR spectroscopy in the tumor volume range of approximately 100-1200 mm3. The MCa showed a constant pH in this volume range; the ratio of phosphocreatine to inorganic phosphate (PCr/Pi) for 160-300 mm3 tumors was 0.33 +/- 0.11 (mean +/- standard deviation) and did not change (0.29 +/- .09) for tumors in the volume range of 600-1200 mm3. In comparison, the Meth A showed a decrease in tumor pH as volume increased from 160-300 mm3 (pH 7.16 +/- 0.4) to 600-1200 mm3 (pH 6.94 +/- .07). Tumor PCr/Pi decreased from 0.70 +/- .16 (160-300 mm3) to 0.33 +/- .16 (600-1200 mm3). The radiation doses for control of MCa-induced tumors in 50% of the treated tumors ranged from 65 (150-250 mm3) to 71 Gy (1000-1300 mm3) and for the Meth-A-induced tumors ranged from 35 (150-250 mm3) to 38 Gy (1000-1300 mm3). These results suggest that 31P NMR spectra may be a qualitative predictor of tumor hypoxia, although further studies of human and rodent tumors are necessary to support this hypothesis. PMID- 2315449 TI - Formation of alpha-deoxyadenosine in polydeoxynucleotides exposed to ionizing radiation under anoxic conditions. AB - When poly(dA), poly(dA-dT), and salmon testis DNA were gamma-irradiated under nitrogen, the major deoxyadenosine damage product (excluding liberated adenine) was identified as the alpha-anomer of deoxyadenosine. The yields of alpha deoxyadenosine from poly(dA), poly(dA-dT), and salmon testis DNA irradiated with a dose of 500 Gy under anoxic conditions were 1.5, 1.3, and 1.3%, respectively. No alpha-deoxyadenosine was detected after irradiation under oxic conditions. The presence of nucleotides with the alpha-configuration at the anomeric carbon atom in the DNA chain may have a significant effect on its tertiary structure and possibly modify its biological activity. PMID- 2315450 TI - Hydrogen peroxide-induced base damage in deoxyribonucleic acid. AB - Aqueous solutions of calf thymus deoxyribonucleic acid (DNA) were exposed to hydrogen peroxide in the presence of air. Base products formed in DNA were identified and quantitated following acid hydrolysis and trimethylsilylation using gas chromatography-mass spectrometry. The yields of these products were dependent upon the hydrogen peroxide concentration, and increased in the following order: 8-hydroxyadenine, cytosine glycol, 2,6-diamino-4-hydroxy-5 formamidopyrimidine, 8-hydroxyguanine, thymine glycol, and 4,6-diamino-5 formamidopyrimidine. Previous studies have shown that these compounds are typically formed in DNA in aqueous solution by hydroxyl radicals generated by ionizing radiation. Hydrogen peroxide is thought to participate in a Fenton-like reaction with transition metals, which are readily bound to DNA in trace quantities, resulting in the production of hydroxyl radicals close to the DNA. This proposed mechanism was examined by exposing DNA to hydrogen peroxide either in the presence of a hydroxyl radical scavenger or following pretreatment of DNA with metal-ion chelators. The results indicate that trace quantities of transition metal ions can react readily with hydrogen peroxide to produce radical species. The production of radical species was monitored by determining the altered bases that resulted from the reaction between radicals and DNA. The yields of the base products were reduced by 40 to 60% with 10 mmol dm-3 of dimethyl sulfoxide. A 100-fold increase in the concentration of dimethyl sulfoxide did not result in a further reduction in hydrogen peroxide-induced base damage. DNA which was freed from bound metal ions by pretreatment with metal ion chelators followed by exhaustive dialysis was found to be an ineffective substrate for hydrogen peroxide. The yields of base products measured in this DNA were at background levels. These results support the role of metal ions bound to DNA in the site-specific formation of highly reactive radical species, most likely hydroxyl radicals, in hydrogen peroxide-induced damage to the bases in DNA. PMID- 2315451 TI - [The effective dosage as the stimulating exposure in fractionated gamma irradiation]. AB - The study of early neurological disturbances (END) in rats after fractionated gamma irradiation with doses of 37.5-225 Gy at dose rate of 30.11 Gy/min has demonstrated that the initial response of animals to pulse ionizing radiation is a function of the electric charge induced by ionizing radiation. A change in the probability of occurrence of each of the END symptoms, with the increased intervals between exposures, is merely an indirect indication of the eliminating mechanisms and is intricately connected with the irritating charge value. The period of dose half-elimination in 16 min. The threshold effective dose rate leading to END is of the order of 2.12 Gy/min. The proposed empiric relationships permit to correlate the probability of END symptom occurrence with the continuous quantitative parameter of fractionated irradiation, that is, with an effective dose as an analogue of the irritating effect. PMID- 2315452 TI - [The possibility of using polarography for the diagnosis of radiation damage]. AB - The polarographic method permitted to register changes in the protein higher structure at radiation doses of the order of tenths Gy. A technique is proposed and optimum conditions found for taking measurements in mammalian serum and plasma in vitro. It is suggested that the proposed technique, having been tested on experimental animals, might be used for an indirect diagnosis of radiation affection in human beings. PMID- 2315453 TI - [A decrease in the efficiency of radiation damage repair in HeLa tumor cells with their preliminary irradiation at low radiation doses (0.1 Gr)]. AB - In experiments with tumor HeLa cells, a study was made of the survival rate of both the whole population and individual clonogenic cells after irradiation within different regimes at a cumulative dose of 4 Gy. The results obtained prompt a conclusion that the preirradiation with a dose of 0.1 Gy decreases the efficiency of repair of radiation-induced damages to cells. PMID- 2315454 TI - [An analysis of the lymphocytes with anomalous nuclei in the peripheral blood of rats subjected to gamma irradiation]. AB - The share of lymphocytes with abnormal nuclei in the peripheral rat blood was found to increase during the first 24 h following irradiation with doses LD0, LD50, and LD100. With LD50 the index under study significantly varied in survived, died and control animals. It is suggested that the occurrence of abnormal nuclei in the peripheral rat blood is the result of the two processes, namely, the mitotic division and apoptotic death of cells. PMID- 2315455 TI - [Kininogenesis and the effect of bradykinin on the level of blood plasma glucocorticoids in irradiated rats]. AB - Kininogenesis is activated after irradiation as well as after the injection of hydrocortisone. Bradykinin, the main component of the kinin system, is a factor that limits the level of blood plasma 11-oxycorticosteroids after its intravenous injection to exposed rats. PMID- 2315456 TI - [The early changes in humoral immunity under the prolonged action of tritium oxide with different dose rates]. AB - Within the dose range from 0.2 to 1 Gy, early changes in the humoral immunity of mice exposed to tritium oxide at varying dose rates have been investigated. The study of the immunity impairment at different stages of immunopoiesis permits to reveal the points (a lymphocyte precursor department) that are mostly affected by radiation, to find the causes of the decrease in the antibody production, and to reveal the relationship between the damages observed the dose absorbed and dose rate of beta radiation. PMID- 2315457 TI - [Protein phosphorylation during mast cell secretion in radioprophylaxis]. AB - A study was made of the role of protein phosphorylation of mast cells and their cytoskeleton upon secretion induced by biogenic amines (histamine and serotonin) and bradykinin, a possible mediator of the effect of MEA, a sulfur-containing radioprotector. The data obtained indicate that the incorporation of phosphate in some proteins of mast cells is an important stage in the process of exocytosis during radioprophylaxis. Cytoskeletal proteins were shown to be involved in mast cell secretion. PMID- 2315458 TI - [The brain phospholipids following the irradiation of animals at a high dosage]. AB - In experiments with albino mice, rats and guinea pigs the effect of ionizing radiation (100 Gy) on brain phospholipids and their fatty acids has been investigated. Upon the development of manifest behavioural disturbances (2 h after irradiation) phospholipid molecules degrade insignificantly. Some changes in the relative content of phospholipids and their fatty acids are mainly found in the rat synaptosomal fraction: this may be responsible for the disturbances in the sensitivity of the receptor apparatus of cell membranes. PMID- 2315459 TI - [The effect of ionizing radiation at superhigh dosages on the ATP content in the rat brain]. AB - The ATP content of rat brain was shown to decrease considerably (20-60%) during the first minutes following high-energy electron irradiation with doses of 300 and 500 Gy. A transient nature of changes and a more pronounced decrease in ATP with increasing radiation dose and manifest neurologic disturbances indicate that the energy metabolism is involved in the pathogenesis of early neurologic disturbances in animals. PMID- 2315460 TI - [Postradiation changes to the systems of active ion transport in the CNS. The content of adenine nucleotides as an index of the energy support for transport]. AB - The postirradiation changes in the adenine nucleotide content and energy charge in large hemispheres of rat brain have been investigated. Dose dependent disturbances have been found in the adenine nucleotide system. Mechanisms of changes in the energy status of nerve cells in radiation disease are discussed. PMID- 2315461 TI - [The effect of L-DOPA on the accumulation of lipid peroxidation products in separate brain structures during irradiation]. AB - A study was made of the effect of L-DOPA on the dynamics of changes in lipid peroxidation products (LPP) and the content of various types of SH groups in certain brain structures (oblongata, cerebellum, visual and sensorimotor cortex) and their synaptosomal fractions upon irradiation. The preadministration of L DOPA to irradiated rats inhibited LPP accumulation, prevented the decrease in the content of various types of thiols and thus exerted an antioxidant effect. PMID- 2315462 TI - [The effect of mexamine on liver mitochondrial function in rats in vivo and in vitro from the aspect of the mechanisms of the pharmacological and radioprotective action of the protector]. AB - The polarographic study of the functional status (FS) of rat liver mitochondria subjected to the effect of mexamine in vivo and in vitro and the hypoxic hypoxia in vivo has revealed various FS changes displaying disconnecting and rotenone like effects and posthypoxic activation. With a mexamine dose of 50 mg/kg in vivo the direct effect of the protector contributes considerably to the mitochondrial FS. Within a wide range of mexamine doses no relationship was found between the pattern of the mitochondrial FS change in the liver and the protective effect with respect to bone marrow. PMID- 2315463 TI - [The mechanism of the radioprotective action of cystamine and mexamine]. AB - It was found that at the time when cystamine and mexamine exert their maximum radioprotective action DNA synthesis rate decreases in bone marrow cells, the ratio between the colony-forming units in the bone marrow and peripheral blood changes, and functional activity of neutrophils increases. PMID- 2315464 TI - [The autoregulation of intracellular oxygen tension and the modification of cellular radiosensitivity. The development of an adaptation hypothesis]. AB - A hypothesis is reported postulating that the range within which the intracellular oxygen content varies with changes in the external oxygenation conditions is responsible for the oxygen-dependent radiosensitivity modification that may be controlled by the diffusion resistance of a cytoplasmic membrane. The adaptation mechanism of intracellular Po2 autoregulation is involved when drastic changes in the oxygen content of the environment occur. As the oxygen content decreases this mechanism provides maximal values of the intracellular Po2 required for optimizing cell viability; the increased oxygen content prevents cells from oxygen intoxication. PMID- 2315465 TI - [The direct action of high doses of gamma quanta and neutrons of different energies on the sympathetic ganglion neurons in the frog]. AB - Irradiation of isolated frog sympathetic ganglia IX-X with high doses caused a long-term depolarization of a single ganglion cell and increase of synaptic activation threshold. The radiation effects observed were not accompanied by the transmission failure. The authors suggest that the changes in the synaptic mechanisms play a minor role in the development of the CNS syndrome. PMID- 2315466 TI - [The effective and ineffective levels of the joint action of 239Pu and gamma radiation according to the change in the ECG indices of dogs]. AB - Effective and ineffective levels of the isolated and combined action of inhaled 239Pu and external gamma radiation on dogs were estimated by some changes in the ECG. Specific share of each factor in the combined effect and the quality coefficient of 239Pu were estimated by two criteria of changes in the ECG. The data were extrapolated to man by the most reliable criterion, that is, the decrease in the ECG voltage indicated by the sum of R I, II, III waves. PMID- 2315467 TI - Perfusion thallium imaging of type I diabetes patients with end stage renal disease: comparison of oral and intravenous dipyridamole administration. AB - Eighty patients with type I diabetes and end stage renal disease were prospectively evaluated for coronary artery disease with dipyridamole-thallium 201 scintigraphy and quantitative coronary angiography. Forty patients received dipyridamole orally, and 40 received it intravenously. The prevalence of coronary artery disease was 53%. There were no significant differences in the accuracy of the two dipyridamole tests (sensitivity = 85%, specificity = 85%, accuracy = 85% for the oral group; sensitivity = 86%, specificity = 72%, accuracy = 79% for the intravenous group). Combining the 80 patients into a single group gave a sensitivity of 86%, a specificity of 79%, and an accuracy of 83% for the detection of coronary disease. Although the accuracy of this test in this patient population was similar to that previously reported for other groups, the prevalence of disease was high and resulted in a low predictive value of a negative test (83%). PMID- 2315468 TI - Cerebral palsy: initial experience with Tc-99m HMPAO SPECT of the brain. AB - The outlook for children with cerebral palsy is determined by the severity of motor problems and the presence of associated disabilities, in which early detection remains a medical challenge. The authors studied 13 children (aged 13 months to 12 years) with cerebral palsy by means of single photon emission computed tomography (SPECT) of the brain with technetium-99m hexamethylpropyleneamineoxime (HMPAO). In all children with hemiplegia, SPECT demonstrated hypoperfusion in the hemisphere contralateral to the motor deficit. SPECT demonstrated normal findings in patients with mild diplegia; bilateral hypoperfusion in the superior motor cortex in patients with moderate di- or tetraplegia; and bilateral reduction of perfusion in the superior motor, inferior motor, prefrontal, and parietal cortices in patients with severe di- or tetraplegia. Results suggest that Tc-99m HMPAO SPECT of the brain is a valuable complementary tool for thorough neurologic assessment in cerebral palsy. PMID- 2315469 TI - Right carotid artery ligation in neonates: classification of collateral flow with color Doppler imaging. AB - Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure for neonates that involves permanent ligation of the right common carotid artery. To determine the collateral flow patterns that develop after ligation, 58 infants underwent a total of 115 color Doppler imaging studies during (n = 54), within 1 month after (n = 36), or more than 1 month after (n = 25) ECMO. On the basis of the direction of flow in the right internal carotid artery (ICA) proximal and distal to the right posterior communicating artery (PCoA), 85 of the 115 studies were placed in one of three categories: (a) Anterior communicating artery (ACoA) dominance (n = 22), with retrograde flow in the entire right ICA, was most common during ECMO and was never seen more than 1 month after ECMO. (b) PCoA dominance (n = 47), with antegrade right ICA flow distal to the right PCoA but retrograde proximally, was common during all time periods. (c) External carotid artery (ECA) dominance (n = 16), with antegrade flow throughout the right ICA, was noted in 53% of studies more than 1 month after ECMO but in only 9% of earlier studies. Patterns changed from ACoA to PCoA to ECA dominance in 17 infants, but no change in the opposite direction was noted. PMID- 2315471 TI - Clinical activities of pediatric radiologists in the United States and Canada: 10 year follow-up. AB - The members of the Society for Pediatric Radiology were surveyed in 1989 about their involvement with newer imaging modalities. Results were compared with those obtained in a similar study performed 10 years earlier. The performance and monitoring of imaging studies increased dramatically, with most respondents now being involved with ultrasound (US) and computed tomography (CT), and almost one half involved with magnetic resonance (MR) imaging. When equipment became available, pediatric radiologists were quicker to assume control of MR imaging than US and CT. In most large pediatric centers, imaging with all current modalities and of all organ systems has become the responsibility of pediatric radiologists. These findings are in contrast to those obtained in 1979, when pediatric imaging practices primarily consisted of conventional radiography and fluoroscopy. PMID- 2315470 TI - Intussusception: hydrostatic pressure equivalents for barium and meglumine sodium diatrizoate. AB - The pressures generated by a barium suspension and various solutions of meglumine sodium diatrizoate in water were measured with a manometer. A pressure of 120 mm Hg was produced by a 3.5-foot (105-cm) column of 60% wt/vol barium and a 5-foot (150-cm) column of either a 1:3 or 1:4 solution of meglumine sodium diatrizoate and water. This is the pressure used to reduce an intussusception with air. PMID- 2315472 TI - Rapid acquisition spin-echo (RASE) MR imaging: a new technique for reduction of artifacts and acquisition time. AB - The rapid acquisition spin-echo (RASE) technique combines a short repetition time, a short echo time, and a single excitation pulse sequence with half-Fourier data sampling. This allows for acquisition of 11 strongly T1-weighted sections during a single 23-second breath-holding period. Measurements obtained from volunteers and with phantoms reveal that RASE images have a lower signal-to-noise ratio and contrast-to-noise ratio than do conventional multiacquisition spin-echo (SE) images due to reduced data acquisition. However, liver-spleen contrast and spatial resolution are not affected. Moreover, contrast-to-artifact (C/A) measurements are 77% greater with RASE. When normalized for imaging time, all parameters are significantly higher with RASE, with a C/A per unit time that was 338% higher. Randomized, blinded review of RASE and SE sequences from 20 patients was conducted to evaluate qualitative performance. Excellent to good performances for phase-encoding artifact reduction, edge sharpness, and overall image quality were recorded for 89%, 88%, and 86% of RASE examinations, respectively, versus 41%, 59%, and 47% of conventional SE examinations, respectively. All results were statistically significant with P less than .001. RASE is an easily implemented imaging technique that utilizes widely available existing technology. Its major benefits relate to significant reduction in imaging time, elimination of respiratory artifacts, and the potential for performing dynamic contrast material enhanced screening examinations. PMID- 2315473 TI - Parietal pleural changes in empyema: appearances at CT. AB - The parietal pleura bordering pleural space collections was analyzed with computed tomography (CT) in 35 patients with thoracic empyema, 30 patients with malignant effusion, and 20 patients with transudatory effusion. Enhancement of the parietal pleura was present in 96% of the 25 patients with empyema who underwent contrast material-enhanced examinations. Of the 35 patients with empyema, 86% showed thickening of the parietal pleura, 60% showed thickening of the extrapleural subcostal tissues, and 35% showed increased attenuation of the extrapleural fat. None of the 20 patients with transudatory effusion showed these findings. Of the 30 patients with malignant effusion, eight patients (27%) showed chest wall changes similar to those of the patients with empyema. However, two thirds of these patients had a recognized superimposed complication (ie, sclerotherapy). Contrast-enhanced CT appears to be sensitive to chest wall changes in patients with empyema. CT study of the parietal pleura may help suggest occult pleural space infections and may influence therapeutic decisions that vary with the stage of empyema. PMID- 2315474 TI - Double-contrast barium enema studies: effect of multiple reading on perception error. AB - The images from 60 double-contrast barium enema (DCBE) examinations of patients who had also undergone colonoscopy were reviewed independently by three radiologists. The average radiologist detected 70.2% of the 46 radiologically visible lesions. The reports of the individual observers were combined to generate double and triple reading reports. The corresponding average double and triple reading combinations resulted in detection of 83.3% and 89.0%, respectively, of the visible lesions. These increases in sensitivity over those of the readings of the single observers were clinically and statistically significant. They were, however, accompanied by some decreases in specificity. The results confirm the concept that false-negative perception error is a major problem in the interpretation of DCBE examinations and indicate that multiple reading is an effective way to reduce this error. PMID- 2315475 TI - Aortoenteric fistula and perigraft infection: evaluation with CT. AB - A blinded retrospective study was performed to determine the sensitivity and specificity of computed tomography (CT) in detecting perigraft infection (PGI) and aortoenteric fistula (AEF), rare but devastating complications of aortic reconstructive surgery. Two observers independently reviewed CT scans in 55 cases including AEF (n = 23); PGI (n = 12); and normal, noninfected grafts (n = 20). Each scan was assessed for ectopic gas, focal bowel wall thickening, perigraft fluid, perigraft soft tissue, pseudoaneurysm formation, disruption of the aneurysmal wrap, and increased soft tissue between the graft and surrounding wrap. Comparison of CT findings with operative results revealed that each observer correctly identified as abnormal 33 of 35 cases of PGI either with or without AEF (sensitivity, 94%) and that results were falsely positive in three cases (specificity, 85%). CT findings ranged from large amounts of perigraft soft tissue and ectopic gas to subtle findings of minimal or no abnormalities; thus, strict criteria must be applied to the interpretation of CT scans after aortic surgery. Although CT is not 100% sensitive or specific, the authors conclude that it will continue to be valuable for diagnosing PGI and AEF. PMID- 2315476 TI - In-111-labeled monoclonal antibody immunoscintigraphy in colorectal carcinoma: safety, sensitivity, and preliminary clinical results. AB - A phase I/II prospective clinical trial was performed with indium-111-labeled monoclonal antibody (MoAb) conjugate B72.3-glycyl-tyrosyl N-epsilon diethylenetriaminepentaacetic acid (CYT-103) in 28 preoperative patients with biopsy-proved or suspected colorectal carcinomas. Immunoscintigraphy was performed 2-7 days after infusion of 4.1 mCi (152 MBq) of In-111 labeled to CYT 103 at doses of 0.5, 1.0, 2.0, and 20.0 mg. Surgical and histologic confirmation was available in all cases. Use of In-111 CYT-103 made possible detection of 75% of colorectal carcinomas at doses of 1.0 mg and higher, compared with only 20% detection at the 0.5-mg MoAb dose. Immunohistochemical staining for tumor associated glycoprotein (TAG)-72 in resected carcinoma tissues demonstrated a positive correlation between MoAb imaging and the percentage of cells that expressed TAG-72. One patient suffered an adverse reaction after MoAb infusion. Human antimouse response to CYT-103 developed in 16% of patients. PMID- 2315477 TI - Sphenoid fractures: prevalence, sites, and significance. AB - The computed tomographic (CT) scans of the head of 490 blunt trauma victims were reviewed to establish the frequency of sphenoid fractures. There were 111 patients with craniofacial fractures, 78 of whom had fractures of the sphenoid bone. In 51 of the 78 patients these were associated with complex facial fractures, and in the 27 remaining patients they represented primarily fractures of the skull base. The number of sphenoid fractures not only exceeded those that involved the other bones of the base of the skull, including the temporal bone, but also exceeded the number of fractures of the cranial vault that could be identified with CT. All available charts were reviewed for the patients with sphenoid fractures in order to determine the presence of potentially related injuries. In 21 patients there were complications that included damage to the internal carotid artery, cerebrospinal fluid rhinorrhea, optic nerve damage, superior orbital fissure syndrome, and posttraumatic diabetes insipidus. PMID- 2315478 TI - Osteogenesis imperfecta tarda: appearance of the temporal bones at CT. AB - The computed tomographic findings in the temporal bone of two patients with osteogenesis imperfecta tarda are described. One of the patients had bilateral facial nerve paresis, and both patients presented with hearing loss. PMID- 2315479 TI - Encephalitis caused by human immunodeficiency virus: CT and MR imaging manifestations with clinical and pathologic correlation. AB - To determine the computed tomographic (CT) and magnetic resonance (MR) imaging manifestations of central nervous system (CNS) infection by the human immunodeficiency virus (HIV), the authors analyzed the results of imaging of the CNS in 24 patients with HIV encephalitis confirmed at autopsy. Careful pathologic correlation demonstrated that neither CT nor MR imaging enabled detection of microglial nodules with multinucleated giant cells, the hallmark of HIV encephalitis seen in all 24 affected patients. The most common abnormality observed on images of the CNS was atrophy, demonstrated in 18 patients. Demyelination and vacuolation of white matter tracts accompanying severe HIV infection caused hypoattenuation on CT scans and hyperintensity on T2-weighted MR images. These lesions had no mass effect. MR imaging was more sensitive than CT in the detection of lesions caused by HIV or other superimposed infectious agents. Although it is often difficult to attribute any radiologic appearance to a single etiologic agent in patients with acquired immunodeficiency syndrome, the combination of atrophy and symmetric, periventricular or diffuse white matter disease suggests HIV encephalitis. PMID- 2315480 TI - Dural arteriovenous fistulas: evaluation with MR imaging. AB - The preangiographic diagnosis of cerebral dural arteriovenous fistula (DAVF) can be difficult. The magnetic resonance (MR) images of 12 patients with angiographically proved DAVF were evaluated to characterize the appearance of these lesions and to identify those patients at increased risk for complications. Patients with DAVF demonstrating venous occlusive disease are at higher risk for complications from the arterialized collateral venous system. This venous occlusive disease is demonstrated best at arteriography. The MR imaging appearance of dilated cortical veins without a parenchymal nidus is suggestive of a DAVF with veno-occlusive disease. Eight of the 12 patients in our series demonstrated this finding at angiography. Complications, including infarction and hemorrhage, were identified at MR imaging in eight patients with MR imaging evidence of veno-occlusive disease. At angiography 42% of these complications were not apparent. In one patient with a DAVF draining into an unobstructed right sigmoid sinus, results of MR study were normal. Although patients with DAVF without veno-occlusive disease may have normal findings at MR imaging, DAVF associated with veno-occlusive disease and dilated pial venous drainage can be documented on MR images. This subset of DAVF patients, many of whom were identified only at MR imaging, is at higher risk for complications due to veno occlusive disease. These patients are believed to require more urgent therapy. MR imaging is useful in the pretherapeutic planning for patients with DAVF. PMID- 2315481 TI - Acute hematomas: effects of deoxygenation, hematocrit, and fibrin-clot formation and retraction on T2 shortening. AB - Acute hematomas can appear hypointense on T2-weighted magnetic resonance (MR) images at field strengths as low as 0.35 T. Using Raman spectroscopy to measure blood oxygenation and taking T2 measurements at 2.1 and 9.4 T, the authors examined the relaxation mechanisms acting during deoxygenation, increases in hematocrit, and fibrin-clot formation and retraction. Individual contributions to overall T2 from deoxyhemoglobin and the interactions of water with protein hydration layers in hemoglobin, plasma proteins, and fibrin were measured. Overall T2 values estimated by summing individual relaxation rates were in reasonable agreement with the T2 values of clotted blood. Results suggest that deoxygenation may be most important in T2 shortening, followed by increased hematocrit. T2 shortening from fibrin polymerization was minimal at the field strengths used. Effects of deoxygenation and increasing hematocrit are more sensitive to field strength than fibrin T2 shortening. Effects of fibrin may be more significant at middle and low field strengths. PMID- 2315482 TI - Canine intervertebral disks: correlation of anatomy and MR imaging. AB - Because the structure, maturation, and degeneration of canine intervertebral disks resemble those of humans, the authors developed a model of acute intervertebral disk degeneration in dogs. Herniated disks of 18 dogs were examined with magnetic resonance (MR) imaging and then sectioned with a freezing microtome. On the basis of their morphologic appearance in the freezing microtome sections, most of the lumbar intervertebral disks could be categorized as one of six types. Each type has characteristic features and a distinctive appearance on MR images. Findings of this study--including decreased signal intensity from the intervertebral disk, altered signal intensity in contiguous bone marrow, bulging of the anulus fibrosus, herniation of the nucleus pulposus, and contrast enhancement after intravenous administration of gadolinium diethylenetriaminepentaacetic acid (DTPA)--resemble observations from human clinical studies. Classification of degenerating disks and identification of MR imaging characteristics of each type may improve the interpretation of MR images and recognition of early disk degeneration in humans. PMID- 2315483 TI - Repopulation of marrow after transplantation: MR imaging with pathologic correlation. AB - Sixty-seven magnetic resonance (MR) studies of the lumbar spine were performed in 15 patients with bone marrow transplants, and the appearance of marrow regeneration on MR images was correlated with results of bone marrow biopsy and pathologic examination. After transplantation, T1-weighted MR images of vertebral marrow showed a characteristic band pattern consisting of a peripheral zone of intermediate signal intensity and a central zone of bright signal intensity. Reciprocal changes were identified on short inversion time inversion recovery images. At histologic examination the central zone corresponded to fatty marrow; the peripheral zone corresponded to a zone of regenerating hematopoietic cells. Posttransplantation T1 and T2 relaxation times of the entire vertebral marrow were calculated from the spin-echo images; no statistically significant trends in relaxation times were noted. Knowledge of the normal MR pattern of marrow regeneration after transplantation may be useful in screening for residual marrow disease, determining marrow engraftment, and differentiating marrow repopulation with normal versus malignant cells. PMID- 2315484 TI - Red and yellow marrow in the femur: age-related changes in appearance at MR imaging. AB - T1-weighted magnetic resonance (MR) images of the femur in 77 subjects, aged 1 month to 24 years, were retrospectively analyzed for the distribution and appearance of red and yellow marrow. The subjects were divided into six age groups, and the signal intensity and degree of mottling of marrow in the proximal epiphysis, proximal metaphysis, diaphysis, distal metaphysis, and distal epiphysis were observed and assigned a grade. Bone marrow with low or intermediate to slightly increased signal intensity was considered red marrow, while bone marrow with increased signal intensity was considered fatty marrow. An orderly progression of red to yellow marrow conversion in the femur was appreciated first in the diaphysis (ages 1-10 years) and then in the distal metaphysis (ages 10-20 years), with an adult pattern seen by age 24 years. The MR spectrum of red and yellow marrow differs from the existing macroscopic anatomical data because MR imaging is apparently more sensitive to the presence of microscopic fat in bone marrow. PMID- 2315485 TI - Comparison of digital and conventional musculoskeletal radiography: an observer performance study. AB - Interpretations of 122 musculoskeletal radiographs were compared with interpretations of their digital counterparts at a resolution of 1,024 X 840 X 12 bits. Images were evaluated by four readers and included subtle and nonsubtle abnormalities and normal findings. Joint receiver operating characteristic (ROC) analysis results were averaged over all readers and demonstrated no statistically significant difference between the two imaging methods. High interobserver variability limited identifiable differences. Review of cases with subtle findings on the digital system at a resolution of 2,048 X 1,680 X 12 bits (2.5 line pairs per millimeter) revealed adequate visualization of the abnormality in every case. It is concluded that a resolution of 1,024 X 840 X 12 bits is adequate for the interpretation of many musculoskeletal abnormalities but that a resolution of 2,048 X 1,680 X 12 bits is needed for visualization of some subtle abnormalities. PMID- 2315486 TI - Bone scans with one or two new abnormalities in cancer patients with no known metastases: frequency and serial scintigraphic behavior of benign and malignant lesions. AB - Scintigraphic, radiologic, and clinical follow-up findings were reviewed in cases in which bone scans (n = 301) showed one or two new abnormalities in patients with malignancy but no known metastases. Metastatic disease was confirmed for 25 of 231 scans (11%) with one new abnormality and for 17 of 70 scans (24%) with two new abnormalities. The prevalence of metastases was 0.06 to 0.13 for lesions in all regions of the skeleton, except the sternum (three of six) and the pelvis (10 of 32). On follow-up scans, in the absence of an interval change in therapy, 19 of 21 metastases became more intense, whereas most benign abnormalities either remained unchanged (47%) or resolved (41%). Benign lesions in the ribs, extremities, and pelvis generally resolved within 12-24 months, while most benign skull and spine abnormalities were still apparent after 35-58 months of follow up. PMID- 2315487 TI - Osteosarcomatosis. AB - A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized. PMID- 2315488 TI - Gamma camera image acquisition, display, and processing with the personal microcomputer. AB - The authors evaluated the potential of a microcomputer for direct acquisition, display, and processing of gamma camera images. Boards for analog-to-digital conversion and image zooming were designed, constructed, and interfaced to the Macintosh II (Apple Computer, Cupertino, Calif). Software was written for processing of single, gated, and time series images. The system was connected to gamma cameras, and its performance was compared with that of dedicated nuclear medicine computers. Data could be acquired from gamma cameras at rates exceeding 200,000 counts per second, with spatial resolution exceeding intrinsic camera resolution. Clinical analysis could be rapidly performed. This system performed better than most dedicated nuclear medicine computers with respect to speed of data acquisition and spatial resolution of images while maintaining full compatibility with the standard image display, hard-copy, and networking formats. It could replace such dedicated systems in the near future as software is refined. PMID- 2315489 TI - Research resources in academic radiology. AB - Research resources in academic radiology were investigated by analyzing the responses to a survey from 72 North American institutions. The questionnaire addressed five general areas: department size, departmental resources committed to research, availability of research training, research quality control, and research productivity. The highest correlates of grant productivity included measures of departmental resources committed to research, for example, space devoted to research, size of research budget, and full-time employee support for engineers, physicists, and chemists. In a regression model, measures of the number of engineers employed by a department, the number of attending staff, and the number of training lectures given by engineers were found to be most highly associated with dollar value of grant support. The average level of research resources available at responding institutions was generally low, despite a seemingly strong desire to do quality research. This is evidenced by a strong sentiment among respondents in favor of research training and quality control of research. PMID- 2315490 TI - Selective internal radiation therapy: validation of intraoperative dosimetry. AB - In selective internal radiation (SIR) therapy of hepatic metastases, tumor vasculature is preferentially embolized with high-energy beta-emitting yttrium-90 labeled microspheres. To enable accurate estimation of the resultant absorbed radiation doses to tissues, an intraoperative beta detection probe is used to scan the liver surface. The validity of the response of this probe to Y-90 and its clinical application were assessed with a phantom containing varying activities and with biopsy samples obtained from patients being treated with SIR therapy. A linear relationship was found between the probe counts taken from the biopsy samples and the calculated tissue radiation doses from the specific activities of each sample. This relationship was repeated with probe counts determined against a water phantom containing various activities of Y-90. The probe was shown to respond minimally to bremsstrahlung. The use of the probe in measuring tissue radiation doses at laparotomy provides the opportunity to control dose administration during SIR therapy. In this way, subtherapeutic exposure of normal tissue can be assured while tumor tissue receives maximal radiation levels. PMID- 2315492 TI - Measurement of pulmonary parenchymal attenuation: use of spirometric gating with quantitative CT. AB - A new approach to reproducible measurement of lung attenuation and structure by means of respiratory-gated computed tomography (CT) was developed. The patient breathes through a microcomputer-controlled pocket spirometer during the complete CT examination, starting with a measurement of the vital capacity. At a user selected respiratory level, the CT scan is triggered and air flow is inhibited mechanically. To exclude operator-related reproducibility errors, evaluation is based on semiautomated algorithms that isolate lung parenchyma by fast contour tracing. In a study on one volunteer, measurement of lung attenuation changed by a factor of about 2.6 (-895 to -730 HU) as a function of inspirational status. Reproducibility on the order of 5% or better can be achieved only with tight spirometric control of respiration. PMID- 2315491 TI - The effects of 2.35-T MR imaging on natural killer cell cytotoxicity with and without interleukin-2. AB - The effects of magnetic resonance (MR) imaging on the natural killer (NK) cell cytotoxicity of human peripheral blood mononuclear cells (PBMC) were studied. The possibility that prior exposure of PBMC to MR imaging might alter the effectiveness of interleukin-2 (IL-2) in enhancing NK cell cytotoxicity was also investigated. PBMC from 10 healthy subjects were used as effector cells, and target cells were three different types of cancer cells: K-562, OV-2774, and Clone-A. MR imaging exposure of effector cells was performed in a 2.35-T static magnetic field for 50 minutes. The chromium-51-release assay was used to determine NK cell cytotoxicity. NK cell cytotoxicity was greater against K-562 target cells than against Clone-A target cells, but in neither case was cytotoxicity affected by prior exposure of PBMC to MR imaging. Treatment of PBMC with IL-2 for 2-6 days enhanced NK cell cytotoxicity, and this enhancement was not altered by prior MR imaging exposure of PBMC. PMID- 2315493 TI - Aspiration catheter for percutaneous thrombectomy: clinical results. AB - The clinical application of an aspiration thrombectomy system is presented. The system consists of a 7-F Teflon catheter with a rotating coaxial propeller-tipped wire. Thrombectomy was successful in treating occlusion of two femoropopliteal arteries and one hemodialysis implant but was not completely successful in a draining shunt vein. Preliminary results are encouraging; mechanical thrombectomy may offer an alternative to local lysis therapy. PMID- 2315495 TI - Anterior cruciate ligament: oblique sagittal MR imaging. AB - Optimal visualization of the anterior cruciate ligament with magnetic resonance imaging requires oblique sagittal imaging planes. Between 10 degrees and 20 degrees of external rotation of the knee is considered ideal. While the knee may normally assume this amount of obliquity in the relaxed position, the orientation of the imaging plane is not guaranteed. Many imagers can perform oblique sagittal imaging, but the operator must set the proper degree of obliquity for the examination. A simple template was devised to facilitate this process, resulting in more consistently oriented imaging planes. The template can be reproduced by photocopying the diagram provided onto a transparency. PMID- 2315494 TI - Celiac plexus neurolysis with the modified transaortic approach. AB - Celiac plexus block with alcohol was performed to relieve pain in 124 patients with abdominal malignancies. A transaortic technique was employed in which a single needle was advanced from a left posterior paramedian approach through the aorta to deposit anesthetic agent directly onto the celiac plexus. Ninety-one percent of patients experienced marked pain relief. No major hemorrhagic or neurologic complications were encountered. The transaortic method of celiac block is as effective as, easier to perform, and may be safer than the classic two needle technique. PMID- 2315496 TI - Demonstration of the scapholunate space with radiography. AB - The importance of radiographic evaluation of the scapholunate space, which should not be wider than 2 mm, has been well established in cases of wrist injury. Unfortunately, the assessment of this space is not accurately determined with routine posteroanterior (PA) radiographs, because the scaphoid and lunate bones often overlap. Moreover, the exact portion of the scapholunate space that should be measured has never been clearly defined. Nine wrists with a scapholunate space no wider than 2 mm and without chondrocalcinosis were studied by means of plain routine views and special projections, transaxial and coronal computed tomographic scans, and dissection to determine the precise orientation and anatomy of this space. A PA radiograph with 10 degrees of tube angulation from the ulna toward the radius best demonstrated the scapholunate space. This space should be measured at the level of the midportion of the flat lateral facet of the scaphoid. PMID- 2315497 TI - Gadolinium-enhanced MR angiography. AB - Experience in three patients (one each with meningioma, pineal tumor, and prominent jugular bulb) illustrates that magnetic resonance (MR) angiography can benefit from the administration of gadolinium diethylenetriaminepentaacetic acid. Data were acquired with a three-dimensional velocity-compensated (fast imaging with steady-state precession) sequence. MR angiograms were obtained with a ray projection algorithm by using maximum intensity values. Portions of the vascular anatomy--particularly venous structures and smaller arteries--were better portrayed on the postcontrast than on the precontrast angiograms. Enhancing lesions were also seen on the projection images. Enhancement of dura and extracranial tissues (sinus and nasal mucosa) can obscure vascular detail. PMID- 2315498 TI - Reversal of tumor location on MR images. AB - After repair work was performed on a magnetic resonance (MR) imager, images of the brain were obtained from a patient with an acoustic neuroma on the left side. On the images, the tumor appeared to be on the right side. The reversal occurred due to a reversal of gradient wire connections. To prevent such an event after MR imager repair, a phantom with side markers should be imaged. PMID- 2315499 TI - Percutaneous transjejunal access to the biliary system. PMID- 2315500 TI - Zones of increased perfusion (hot spots) on perfusion lung scans. PMID- 2315501 TI - Perforation of the inferior vena cava with aortic and vertebral penetration by a suprarenal Greenfield filter. PMID- 2315502 TI - Academic radiology and research: a fresh approach. PMID- 2315503 TI - Uterine cervical carcinoma: comparison of CT and MR findings. AB - Thirty patients with uterine cervical carcinoma underwent computed tomography (CT), magnetic resonance (MR) imaging, and surgical exploration. MR imaging was superior to CT in visualization of the tumor. MR imaging had an accuracy of 77% in the assessment of thickness of cervical stromal invasion. The accuracy rates of these modalities for parametrial evaluation were 78% for clinical evaluation, 70% for CT, and 92% for MR imaging. The overall accuracy rates for tumor staging were 70% for clinical evaluation, 63% for CT, and 83% for MR imaging. MR imaging is superior to clinical evaluation and CT in parametrial evaluation and the staging of uterine cervical carcinoma. PMID- 2315504 TI - Subacute scrotal pain: evaluation of torsion versus epididymitis with MR imaging. AB - Torsion knot and whirlpool patterns result from the twisting of the spermatic cord, which produces distortion of cord structures. These two findings, along with spermatic cord vascularity, were used to prospectively differentiate testicular torsion from epididymitis in 11 patients with subacute scrotal pain who underwent magnetic resonance (MR) imaging. The final diagnosis was established clinically in four patients and surgically in five. MR imaging enabled the recognition of each entity without error. Retrospective review of findings highlighted other potential discriminating features, the most important of which were testicular size and vascularity. Because of its ability to highlight vessels and detail normal and abnormal intrascrotal anatomy, MR imaging in this small series enabled the differentiation of subacute torsion from epididymitis with 100% accuracy. This high degree of accuracy warrants further investigation. PMID- 2315505 TI - Oxygen free radical involvement in urinary Tamm-Horsfall protein excretion after intrarenal injection of contrast medium. AB - To discover whether the increase in urinary excretion of Tamm-Horsfall protein (THP) is mediated by oxygen free radicals generated after injection of contrast medium, the authors tested the hypothesis that inhibition of oxygen free radical production after injection of sodium methylglucamine diatrizoate or iothalamate sodium diminishes urinary THP excretion. In three groups of dogs, kidneys received continuous infusions of either superoxide dismutase (SOD) and normal saline (six dogs), heat-inactivated SOD and normal saline (six dogs), or normal saline alone (four dogs). Urinary THP excretion, glomerular filtration rate, renal blood flow, mean arterial pressure, and renal venous malondialdehyde concentrations were measured before and after administration of contrast medium to each kidney. During the postcontrast period, SOD significantly attenuated the increase in urinary THP excretion, accompanied by an attenuated increase in renal venous malondialdehyde concentration. Heat-inactivated SOD did not attenuate renal hemodynamics or urinary THP excretion. The use of another contrast medium, iothalamate sodium, similarly increased urinary THP excretion. These results show that intrarenal administration of contrast medium induces a transient increase in urinary THP mediated in part by oxygen free radical damage to the kidney. Thus, THP may be a marker of renal tubular injury after injection of contrast medium. PMID- 2315506 TI - Radiolabeled antifibrin antibody in the detection of venous thrombosis: preliminary results. AB - The recent development of monoclonal antibodies against components of coagulated blood may provide new approaches to the diagnosis of venous thrombosis. Scanning with an indium-111-labeled Fab fragment of a murine monoclonal antifibrin antibody (59D8) and ascending contrast venography were performed in 33 patients. Images of the calves, popliteal fossae, thighs, and pelvis were obtained immediately, 4-6 hours, and 24 hours after injection of 2 mCi (74 MBq) of the antibody. All images were read in a blinded manner. Findings in both studies were positive in 28 patients and negative in three. In 19 patients not undergoing heparin therapy, 19 specific anatomic sites were positive on venograms and 29 were positive on antibody images (19 sites matched). In 14 patients undergoing heparin therapy, 34 sites were positive on venograms and 27 were positive on antibody images (22 sites matched). In most patients, positive results were noted within 1 hour of antibody injection. No adverse effects were noted with the antibody preparation. Preliminary data suggest that antifibrin antibody imaging is sensitive in detecting clots, is safe to use, and may have a role in diagnosing and managing venous thrombosis. PMID- 2315507 TI - Tubo-ovarian abscesses: CT-guided percutaneous drainage. AB - The results of computed tomographic (CT)-guided percutaneous drainage in eight patients with tubo-ovarian abscesses are reported. Seven patients (88%) recovered without surgery and required no further treatment. One patient had marked clinical improvement but still required a posterior colpotomy. No complications occurred. One patient had a recurrence of symptoms 20 months after the procedure that represented a new infection. The role of CT-guided percutaneous drainage in tubo-ovarian abscesses as well as an analysis of the technical aspects associated with a successful procedure are discussed. PMID- 2315508 TI - Flexible tantalum stents implanted in aortas and iliac arteries: effects in normal canines. AB - Vascular endoprostheses made of knitted tantalum wire and expanded over angioplasty balloons were placed into aortas or iliac arteries of 14 normal dogs. Twelve stents were placed into the infrarenal abdominal aorta and two stents in the left common iliac arteries by the left carotid artery approach. To firmly expand the stent against the vascular wall, nominal stent sizes 0.5-1.0 mm larger than the measured arterial diameter were required. Arteriography performed at specified follow-up intervals showed no evidence of thrombi or emboli; all side branches (lumbar arteries) covered by the stents remained patent. Vascular diameter decreased minimally at 8 and 26 weeks, associated with histopathologic evidence of neointimal buildup. This buildup was highest at 8 weeks (mean, 313 microns) and was slightly less at 26 weeks (mean, 223 microns). Almost complete coverage by endothelium was seen as early as 3 weeks. It is concluded that the flexible tantalum wire stents are well tolerated by the arterial wall and become quickly endothelialized. No excessive neointimal buildup was observed during the 6-month study. PMID- 2315509 TI - Expandable tubular stents for treatment of arterial occlusive diseases: experimental and clinical results. Work in progress. AB - The balloon-expandable vascular prosthesis consists of a flexible, knitted tantalum wire mesh tube. To demonstrate its pliability, this prosthesis was tested experimentally in 10 mongrel dogs by implanting it into the proximal femoral arteries. The maximum follow-up time was 1 year. On the basis of the experimental results, in which there was no relevant stenosis, occlusion, or migration of the vascular prosthesis, nine patients were treated: one with iliac artery occlusive disease and eight with superficial femoral artery (SFA) occlusive disease (four reocclusions after angioplasty and four unsatisfactory primary angioplasty results). One SFA lesion was treated with the crossover method from the contralateral side. All implants remained patent without hemodynamically significant stenoses, with the longest observation time being 6 months. Flexible, expandable vascular prostheses are promising adjuncts to angioplasty. PMID- 2315510 TI - Imaging of energy metabolites (ATP, glucose and lactate) in tissue sections: a bioluminescent technique. PMID- 2315511 TI - The correlation between excessive vitreal protein levels, prostaglandin E2 levels, and the blood retinal barrier. AB - Changes in vitreal protein and prostaglandin E2 (PGE2) concentrations, as well as chorioretinal in vitro PGE2 production, were studied in rabbit eyes following Neodymium (Nd):YAG laser retinal exposure. Laser exposure was associated with an enhanced vitreal PGE2 concentration throughout a two-week observation period, with highest levels on days 1 and 7 after exposure (a 5.3 and 4.7 increase above baseline, respectively). A transitory 50% elevation above baseline in vitreal protein levels was observed in the laser-exposed eyes during the second week after exposure. Laser exposure was also associated with an enhancement in the in vitro chorioretinal PGE2 production, which varied throughout the observation period, and was more pronounced during the first week after exposure, when levels were four times higher than baseline. Initially PGE2 vitreal levels were closely related to excessive in vitro production. However, during the second week after exposure, evidence of such correlation was lacking, but PGE2 vitreal levels coincided with a small increase in vitreal protein levels. It is suggested that disruption of the blood retinal barrier by the long-term exposure to mildly elevated vitreal PGE2 levels was accountable for protein leakage, which might have affected PGE2 removal mechanisms. PMID- 2315512 TI - Indomethacin enhances histamine-induced pulmonary hemodynamic changes. AB - To determine the role of prostaglandins in porcine pulmonary hemodynamic changes caused by histamine, we compared responses to intravenous histamine with and without pre-treatment with the cyclo-oxygenase inhibitor, indomethacin. In anesthetized pigs, pulmonary artery pressure (Ppa), pulmonary arterial wedge pressure (Ppaw), left ventricular end diastolic pressure (Plved) and cardiac output (Q) were measured repeatedly for 30 minutes, following a 1 ml intrajugular injection of histamine 0.6 microM/kg (n = 6), the identical histamine dose after pre-treatment with indomethacin 5 mg/kg (n = 7), or normal saline (n = 5). Pulmonary arterial resistance (Ra) and pulmonary venous resistance (Rv) were calculated as (Ppa-Ppaw)/Q and (Ppaw-Plved)/Q respectively. Indomethacin pre treatment caused 2-fold greater increases in Ra and Rv with histamine and more prolonged changes. We conclude that inhibition of a vasodilatory prostaglandin released from pulmonary endothelial cells results in unopposed pulmonary vasoconstriction, thereby augmenting pulmonary resistance changes due to histamine. PMID- 2315513 TI - [The nightmare continues. Life after the occupation time in survivors and their descendants]. AB - In the physical and psychical suffering of former concentrations camp inmates, their families, and descendants Auschwitz is as real as ever. The author reports on his own encounters with victims and on the protracted consequences of the camp experience. The author comments on the difficulty of handling the topic of Auschwitz both in Poland and in the Federal Republic. PMID- 2315514 TI - [Concentration camp imprisonment and psychological traumatization]. AB - The author reports on a Norwegian investigation extending over more than 30 years, which showed that, apart from a few exceptions, all former concentration camp inmates and prisoners in Nazi jails manifest permanent physical and psychic damage. On the basis of these findings the Norwegian government has established a generous statutory compensation program. Unlike its counterpart in the Federal Republic of Germany, this program does not require applicants to demonstrate the cause of illness or its consequences in each case. The method of the investigation is presented in detail. PMID- 2315515 TI - [Derealization and repetition]. AB - The psycho-technique of "derealization" helped the majority of the German population that had been loyal to the Hitler regime to escape from their historical responsibility in 1945. The derealization of an historical era of collective history and of the corresponding phases of their individual histories saved these people the work of self transformation and opened the way to an unwitting repetition. In the unending debates around Nazi war criminal and their accomplices, the paramount issue is to refuse the "normality" of this derealization. PMID- 2315516 TI - [Long-term psychological stress as a traumatic syndrome--possibilities of a single therapeutic consultation. Sanctuaries Counseling Team]. AB - The paper begins with a description of the power relations under which youth live in the South African township "Leandra". This leads into a discussion of the sort of therapeutic help, often consisting of no more than a single interview session, that can be offered under these conditions. PMID- 2315517 TI - [Denial in adolescence. Some contradictory aspects]. AB - Adolescents are simultaneously subject to extremely divergent feelings of strength and of weakness and dependency, aggravated by intense regressive longings. In order to tolerate and master these feelings, adolescents commonly employ the defense of denial. This may result in splitting. A case except shows how such a defensive strategy may hinder or further psychic development. PMID- 2315518 TI - [Delusion and dreams in "Death in Venice". Thomas Mann's consequential reading of Freud in 1911]. AB - The author shows by means of literary comparisons that in "Death in Venice" and The Magic Mountain, Mann was strongly influenced by Freud's psychoanalysis, in particular by the latter's work "Delusion and dreams in W. Jensen's 'Gradiva'." PMID- 2315519 TI - [Greetings of the President of the Italian Association of Medical Radiology and Nuclear Medicine]. PMID- 2315520 TI - [Pseudocoarctation of the aorta. Description of a case]. PMID- 2315521 TI - [Dissociation of radiocolloid accumulation and hepatobiliary tracer in a patient with liver adenoma]. PMID- 2315523 TI - [Current role of CT in pediatric ophthalmology]. AB - In spite of the recent and substantial improvements in MR technique, some problems still exist relative to its applications in routine clinical exams in pediatric ophthalmology. The main problems are: inadequate MR equipment, long examination time, and MR inability to demonstrate intraocular calcifications. Ocular and orbital ultrasound (US) studies are highly operator-dependent, and US utility has been especially described in evaluating ocular, but not orbital, lesions. In order to verify the actual role of CT in pediatric ophthalmology, the CT scans of 58 children with ophthalmologic pathologies, performed over a 2-year period, were reviewed and compared with definitive diagnoses. Seven separate CT findings for each pathologic condition were independently analyzed and correlated with histology. In agreement with other CT series, optic nerve gliomas were invariably intraconal, whereas histiocytosis-X, Ewing's sarcoma, olfactory neuroblastoma (esthesioneuroblastoma), metastatic neuroblastoma and nephroblastoma were extra-conal. Rhabdomyosarcoma, principally extraconal, frequently involved the intraconal and preseptal spaces, with permeative destruction of the osseous orbit and frequent intra/extracranial spread. Orbital spread was mainly observed in vascular tumors. CT showed great accuracy in evaluating punctuate calcifications in retinoblastomas and in metastatic neuroblastomas, and bone fragments within a zone of destruction in histiocytosis X. Various characteristics of CT attenuation values were observed in pathologic tissues, and high attenuation and marked contrast enhancement were particularly observed in metastatic neuroblastomas and rhabdomyosarcomas. In congenital orbital abnormalities and inflammatory diseases, CT readily detected ocular malformations (microphthalmos and colobomata).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2315522 TI - [Cerebral hemorrhage: initial experiences with magnetic resonance imaging]. AB - The authors employed MR imaging to examine 29 hematomas (21 spontaneous, 1 traumatic, 2 vascular malformative, and 5 intratumoral). All images were acquired with a 1.5 T superconducting magnet (Signa, General Electric). The different features hemorrhagic collections may present with on MR images and their temporal evolution depend on their dimension, on the different water content of the hematoma and adjacent tissues, on the peripheral macrophage border, and, above all, on the presence of hemoglobin breakdown products, some of which are paramagnetic. The latter is the most important feature as to the nature of the lesion and allows hematomas to be classified as: 1) Acute (1-7 days): presence of intracellular deoxyhemoglobin. 2) Subacute (8-30 days): 2A, intracellular methemoglobin; 2B, intra- and extracellular methemoglobin; 2C, totally extracellular methemoglobin. 3) Chronic (from 30 days on): thick macrophages hemosiderin rim with/without fluid methemoglobin content. The interpretative difficulties initially met caused the authors to arrange schemes, based on the literature data on the subject, to be used as an useful interpretative tool in most of the cases observed. PMID- 2315524 TI - [Magnetic resonance in the study of aseptic necrosis of the femur head]. AB - Avascular necrosis (AVN) of the femoral head is a common clinical problem due to the frequent use of corticosteroids and to the high incidence of hip fractures from osteoporosis and traumas. In order to demonstrate MR diagnostic capabilities, 31 patients (62 hips) were studied with MR imaging, CT, and conventional radiology. The patients had already been diagnosed as having AVN of the femoral head, or the condition was clinically suspected. MR staging of the disease was compared with CT staging and with plain radiographs. The authors suggest new MR staging method and adapt the radiographic classification developed by Ficat, Arlet, and Lecestre. The results of this comparative study demonstrate MR imaging to be most appropriate in the patients with equivocal/negative radiological/CT findings. On the contrary, MR imaging is unnecessary when AVN has already been diagnosed by means of other imaging modalities, because in these advanced cases MR diagnostic contribution either equals or is inferior to that of CT and conventional radiology. PMID- 2315525 TI - [Significance of computerized tomography in the study of Crohn disease]. AB - Twenty-six patients affected with Crohn's disease were studied by means of CT. The method demonstrated transmural fistulas in 2 cases, and bowel wall thickening in all patients. In our series of cases, the advantages of CT over conventional radiology lay in the fact that the former allowed the evaluation of associated mesenteric pathologies (e.g. fibrofatty proliferation, and adenopathies) and demonstrated the presence of abscesses in 4 case. CT findings were in agreement with those from conventional contrast studies in the demonstration of entero enteric fistulas, whereas they yielded additional information in the study of entero-muscular fistulas. Associated pathologies in other organs were found in 5 patients--i.e. fatty infiltration of the liver and cholelithiasis. CT is not useful in demonstrating early mucosal damage in Crohn's disease, but it should be regarded as a complementary method to conventional barium studies. As a matter of fact, CT is fundamental in the evaluation of associated mesenteric pathologies and of other complications which can affect therapeutic management. PMID- 2315527 TI - [Acceptance test after installation of a radiotherapy simulator]. PMID- 2315526 TI - [Immunoscintigraphy in the diagnosis of choroid melanoma]. AB - This study was aimed at evaluating the role of 99mTc-labelled anti-melanoma antibodies as in vivo tumor markers in the diagnosis of uveal melanomas. Usually, neither conventional semeiological techniques nor more recent diagnostic imaging methods allow a differential diagnosis to be made of benign and malignant intra ocular tumors. Immunoscintigraphy was employed to examine 9 patients with monolateral reduction of sight, and photopsy. All patients were previously submitted to funduscopy, fluorescein angiography, and US. Four hours after iv injection of 370 MBq of 99mTc F(ab1)2, we obtained 500,000-count images of skull, abdomen, and thorax, with a computerized gamma camera equipped with a general purpose collimator. A SPET of the head followed the conventional examination. Our first results seem promising enough for further study to be carried out to assess immunoscintigraphy specificity in the diagnosis of uveal melanoma. PMID- 2315528 TI - [MR study of the carpal scaphoid. Normal anatomy]. PMID- 2315529 TI - The greening of hospitals. PMID- 2315530 TI - The business of nursing. GST and health care: the debate is just beginning. PMID- 2315531 TI - Checking up on environmental health. PMID- 2315532 TI - The message is coming in loud and clear. PMID- 2315533 TI - Violence against nurses: an ounce of prevention is worth a pound of cure. PMID- 2315534 TI - Colleagues need pat-on-the-back, not back-stabbing. PMID- 2315535 TI - Greater respect needed for nurses returning to work force. PMID- 2315536 TI - [Right-sided infectious endocarditis. Experience with a series of 35 patients]. AB - From 1978, 35 patients with right-sided endocarditis were treated at our hospital. There were 25 male and 10 female patients, with ages ranging from 14 to 77 years. The cause was intravenous drug abuse in 27 cases. Positive blood cultures were obtained in 29 cases, isolating staphylococcal organisms in 26 of them. Two-dimensional echocardiography was performed in 30 patients, confirming the diagnosis in 27 of them (90%). Vegetations were found in 25 patients and perivalvular abscess was seen in 4 patients. The management was medical only in 32 patients. Three patients were operated on because of failure to control pyrexia and heart failure, performing total tricuspid valvectomy in two, and only partial in the third one. All the 3 patients had perivalvular tricuspid abscess. There were 2 hospital deaths (5.7%), because of septic shock in drug abusers, one of them after a tricuspid valvectomy. In our experience, right-sided endocarditis is mainly associated with drug abusers and staphylococcal organisms. Two dimensional echocardiography plays an important role in the diagnosis of this entity. In our series the size of vegetations does not play a role in selection of surgical candidates. The presence of perivalvular abscess was the only predictive factor for surgery. Only a few patients do not respond to medical therapy. In those cases the elective surgical procedure in our criterion and in our patients is tricuspid valvectomy without valve replacement, or if possible, the use of reconstructive or reparative approaches. PMID- 2315537 TI - [Utility of myocardial scintigraphy with Tc-99m methoxy-isobutyl-isonitrile in the diagnosis of coronary disease]. AB - We have studied 24 patients (21 males and 3 females) with coronary artery disease. Stress and rest myocardial scintigraphy was performed in all cases with 15-20 mCi of Tc99m methoxy-isobutyl-isonitrile. The examination was done in 2 sessions. Usually the stress scan was obtained and within 2-4 days the rest study was obtained. All patients underwent selective coronary arteriography within a week of the scintigraphy and, in 13 cases, rest radiologic ventriculography was also performed. In 5 patients coronary arteriography and myocardial scintigraphy were normal. In 19 cases the coronary arteriography showed lesions, the myocardial scintigraphy showed ischemia or necrosis in 17 of them and was normal in two. To localize the pathologic vessel the myocardium was divided into 3 segments and segmentary analysis localized the abnormal coronary artery in 51 out of 72 cases. The best availability of the new myocardial agent and the results obtained make it a good tracer for myocardial studies. PMID- 2315538 TI - [Double-outlet right ventricle with mitral atresia. Study of 9 cases]. AB - Double-outlet right ventricle with mitral atresia is an uncommon anomaly with a few cases reported in the literature. We present 9 cases of this malformation that have been diagnosed by two-dimensional echocardiography (7 cases), cardiac catheterization (9 cases) and anatomical study (2 cases). We classify them into two groups according to whether or not they have associated pulmonary stenosis. The dominant symptoms were cyanosis and hypoxemia in the first group and cardiac insufficiency signs in the other. The left ventricle was hypoplastic in eight and normal in the one with tricuspid overriding. Six of the cases had ventricular septal defect. The great arteries were in normal relationship in 4 cases, with D malposition in 3 cases and side-by-side in 2 cases. Rashkind atrial septotomy was performed in 5 patients, but was effective only in two. Palliative surgical treatment was performed on six of them. The actual survival rate is 44%. PMID- 2315539 TI - [Aging and efficiency of the baroreflex arc. Analysis of a large sample of normal individuals studied with a computerized technic]. AB - Previous studies, with manifold contradictions, have shown the baroreflex progressive damage in the elderly. A group of 178 normal subjects, between 11 and 88 years age, were investigated by measuring their blood pressures and R-R intervals while at rest and during the Valsalva manoeuvre, deep breathing at 6 breaths/min, and standing up from a lying position. The parasympathetic parameters decreased with ageing; mean heart rate and its response during standing up diminished, suggesting a cardiac ortho-sympathetic alteration; and basal blood pressures increased, while its responses at the last manoeuvre did not change. All this indicates that cardiac parasympathetic activity is reduced and vascular ortho-sympathetic activity--C1 group--is increased. Probably, the cardiac ortho-sympathetic findings are originated by the receptors--because of the C1 neuronal hyperactivity. The destruction of inhibitory afferents with ageing could explain this hyperactivity. PMID- 2315540 TI - [Right aortic arch with retro-esophageal aorta. Diagnosis by computerized axial tomography]. AB - The case of a patient with right aortic arch and retro-esophageal aorta associated with a perimembranous ventricular septal defect with a mild fibrous subaortic stenosis is presented. The existence of the retro-esophageal segment of the aorta was confirmed by left ventriculography and computerized axial tomography. This patient is the first to be diagnosed by axial tomography in our country. PMID- 2315541 TI - [Acute myocardial infarction secondary to non-penetrating thoracic trauma]. AB - We present a case of acute myocardial infarction located anteriorly in a healthy young man who suffered a blunt chest trauma following a motor vehicle accident, with coronarographic evidence of intimal dissection of the left anterior descending artery and evolution to ventricular aneurysm. We comment on the rare incidence of this entity and the mechanism involved in this case, a coronary contusion with subsequent intimal dissection. PMID- 2315542 TI - [Atrioventricular block at the nodal level and block of an accessory pathway during percutaneous mitral valvuloplasty]. AB - We describe the simultaneous occurrence of a temporal complete atrioventricular block and a persistent disappearance of preexcitation, in a patient with rheumatic mitral stenosis and a ventricular preexcitation, after an effective percutaneous mitral valvuloplasty. These conduction disturbances were attributed to atrioventricular node and paraseptal atrioventricular pathway trauma, due to transseptal manipulation during the mitral valvuloplasty. PMID- 2315543 TI - [Biatrial recurrence of a left atrial myxoma]. AB - A biatrial myxoma was diagnosed by 2D echocardiography in a man who was minimally symptomatic. Five years previously another similar tumour, located in the left atrium, attached to the interatrial septum, was excised. Similar histological features were present in both cases. The rarity of biatrial recurrence of this sort of myxoma is emphasized. PMID- 2315544 TI - [Thromboembolism with the Ionescu-Shiley bovine pericardial bioprosthesis. Long term results (11 years)]. AB - With the aim to asses the thrombogenicity of "treated" bovine pericardial tissue, the incidence of thromboembolism with Ionescu-Shiley pericardial bioprostheses was analyzed in 349 operative survivors since January 1977. A total of 376 valves were available for the study. Mean age was 59 years. Preoperatively atrial fibrillation was present in 68.2% (91.7% of the mitral replacement group) and 62% were in NYHA functional class III-IV; in 10.6% previous embolism had been documented. Early anticoagulation (8-12 weeks) was administered in the first 232 patients (113 mitral replacements, 98 aortic replacements and 21 multiple replacements) and the rest of the patient population had no anticoagulation at all. Thromboembolic events were documented in 13 patients (3.72%) or 0.84% per patient/annum (1.49% per patient/annum for mitral and multiple replacements and 0.13% per patient/annum for aortic replacements). Early thromboembolism was detected in 6 patients (3 months after surgery), all in anticoagulated patients, three being in sinus rhythm. No valve thrombosis was detected in this series. Three patients with late thromboembolism were in NYHA functional class III-IV. Ten thromboembolic events were central (1 died and three had permanent neuro residua). In two the location was peripheral and another one in the kidney. The Ionescu-Shiley pericardial bioprosthesis after 11 years has demonstrated a low thrombogenicity in the absence of chronic anticoagulation. Early anticoagulation does not influence the rate of thromboembolism during this period and therefore we believe that this therapeutic approach is not justified despite the presence of risk factors. PMID- 2315545 TI - [Dysfunction caused by thrombosis in a Hancock mitral bioprosthesis and resolution with heparin]. PMID- 2315546 TI - [Myocardial infarction in a young woman with a left atrial myxoma]. PMID- 2315547 TI - Management of agitated head-injured patients: a survey of current techniques. AB - Traumatically brain-injured (TBI) patients compose a large portion of the population treated in rehabilitation programs. Because of the increase in the number and acuity of agitated clients on an inpatient unit at Michiana Rehabilitation Institute in South Bend, IN, the authors conducted a study to establish what techniques currently are used to manage this population. A questionnaire was sent to 60 rehabilitation facilities throughout the United States, with a 50% return rate. The use of an interdisciplinary team, primary nursing, and one-to-one monitoring were frequently reported staffing patterns. Orientation for one-to-one attendants and self-defense education were noted as beneficial. The use of behavior modification, physical restraints, environmental modifications, and medications were nearly equally reported. Further research to identify the need for and outcome of specific management techniques is recommended. PMID- 2315548 TI - Vulnerability and alcohol and substance abuse in spinal cord injury. AB - Alcohol and substance abuse are methods of coping with the losses experienced as a result of spinal cord injury. Applying the concept of vulnerability to this population is useful to assess those spinal cord injured individuals at risk for developing these maladaptive coping mechanisms. The concept of vulnerability also can be used in planning interventions during initial hospitalization to help these individuals avoid the development of or relapse into alcoholism and/or substance abuse. PMID- 2315549 TI - Rehabilitation nursing novices: changing the acute care mind set. AB - The majority of nurses entering the specialty of rehabilitation have little or no previous rehabilitation experience. Specific strategies are needed to assist new staff in developing skills and concepts congruent with rehabilitation nursing practice. This article describes a two-stage orientation process that has been effective in helping new staff members make the practice transition from acute care to rehabilitation nursing. PMID- 2315550 TI - The functional model in multiple sclerosis. AB - Multiple sclerosis (MS) is a sometimes progressive neurologic disorder of young adults that can result in disability and markedly altered lifestyles. Traditionally, MS has had a negative impact on both the patient and healthcare provider, because there is no known cure and treatments are symptomatic. The Functional Model offers a new way of focusing on MS by evaluating function rather than dysfunction, and by emphasizing healthcare and self-care activities that may help the patient move from dependency to a more independent functional status. This model provides rehabilitation personnel with a tool to design individualized interventions and encourage the patient to focus on strengths rather than weaknesses. PMID- 2315551 TI - Education for rehabilitation nursing. AB - An increasing shortage of rehabilitation nurses is anticipated in the coming decade. This article describes one potential answer to the nursing shortage through a course in rehabilitation nursing for senior baccalaureate students. The unique features of the course included the use of holistic learning experiences that integrate theory and practice. Clinical experiences in critical care units, in intensive rehabilitation settings, and in a variety of outpatient facilities, as well as travels with rehabilitation nurse consultants in the field, provided students with rich perspectives on the scope of rehabilitation nursing practice. Replication of this successful course in other settings has the potential to enhance the recruitment of new graduates into the field of rehabilitation nursing. PMID- 2315552 TI - Direct nursing care given to patients in a subacute rehabilitation center. AB - Direct nursing care observations were performed in a 57-bed head trauma subacute rehabilitation center on four day shifts, three evening shifts, and three night shifts. The type of nursing care and level of personnel providing this care are described. Although nursing assistants give the majority of direct care, the RN still provides most of the psychosocial care that is crucial for these patients and their families. PMID- 2315554 TI - Interaction and living arrangements of older parents and their children. Past trends, present determinants, future implications. AB - This article addresses several specific questions which have arisen from speculation about the impact of recent social, economic, and demographic trends on the older family. The availability of and interaction with children among elderly Americans over the past two decades is examined. Causal models are used to explore the effects of social, economic, and demographic change on family interaction and living with a child. Finally, the implications of these findings for the future are reviewed. Analyses are based on the 1984 National Health Interview Survey Study on Aging and the 1962 and 1975 Survey of the Aged studies. PMID- 2315553 TI - Rehabilitation nursing and the patient: outside influences that affect the level of recovery. PMID- 2315555 TI - Survey of adult day care in the United States. National and regional findings. AB - Before attempting to understand how a relatively new treatment modality such as adult day care (ADC) works, it is useful to understand what it is. To this end, this article describes the structural characteristics of ADC centers and the characteristics of ADC users in the United States and across the four U.S. census regions. A 1986 national census survey of 1,347 ADC centers yielded 974 usable responses (72.3%). Findings indicated that there is great variability in characteristics of ADC across the country. In general, ADC's are well-staffed, well-linked to other agencies, and well-equipped. However, demand and enrollment appeared low. A need for improved oversight and staff in-service training was indicated for a substantial proportion of centers. These and other findings provide the most detailed and comprehensive national and regional descriptions of ADC available to date. PMID- 2315556 TI - Personalization of formal social relationships by the elderly. AB - This article examines the role of formal support services in the lives of elderly residents of HUD-subsidized buildings. Tenants identified a variety of formal roles as important in their lives. The three most central roles were physician (79%), apartment manager (58%), and social worker (51%). Formal roles were an important source of both instrumental and affective support in a wide variety of circumstances. Many individuals in formal roles were considered friends and the highly personalized nature of these relationships was a surprising finding. PMID- 2315557 TI - Comparative neuroprotective effects of pentobarbital, vinpocetine, flunarizine and ifenprodil on ischemic neuronal damage in the gerbil hippocampus. AB - We studied the protective effects of pentobarbital, vinpocetine, flunarizine, and ifenprodil on delayed neuronal death using Mongolian gerbils. The animals were allowed to survive for 7 days after 5 min of cerebral ischemia induced by bilateral occlusion of the common carotid arteries. Hippocampal cell loss was quantified histologically 7 days following ischemia. Intraperitoneal application of pentobarbital (40 mg/kg) 30 min and vinpocetine (50 and 100 mg/kg) 10 min before ischemia significantly reduced neuronal cell loss in the CA1 sector. However, the intraperitoneal administration of flunarizine (10 and 30 mg/kg) and ifenprodil (10 and 30 mg/kg) 15 min before ischemia was not protective. The results suggest that pentobarbital and vinpocetine prevent ischemic neuronal damage, but not flunarizine and ifenprodil. These findings are of interest in relation to the mechanism of delayed neuronal death. PMID- 2315558 TI - Microcalorimetric studies on metabolism of hepatic tissue. I. A methodological study of normal tissue. AB - In the present study, the heat production of liver biopsies (5-8 mg) was measured by a microcalorimetric technique. Tissue incubated in Leibowitz L-15 medium (L 15) showed a higher metabolic rate compared to tissue incubated in a medium without substrate 2.8 microW/mg and 1.75 microW/mg, respectively. Heat production was found to be related to weight density. No difference in the metabolic rate was found after organ perfusion in comparison to nonperfused liver. Storage in medium L-15 at 4 degrees C caused a lower rate of heat production, but if the tissue was stored in an electrolyte balance solution without substrate, no difference was seen compared to fresh tissue. Recording heat production with the present calorimetric technique is relatively simple and rapid and allows measurement of small samples. PMID- 2315559 TI - Microcalorimetric studies on metabolism of hepatic tissue. II. Measurements of ischemic tissue. AB - Biopsies of ischemic livers demonstrated a significantly higher rate of heat production when incubated in Leibowitz L-15 medium compared to incubation in modified Eagle's solution (P less than 0.01). A maximal reduction of 25% in the rate of heat production was observed after 60 min of induced ischemia. Liver tissue undergoing reperfusion showed complete and partial recovery after 60 and 90 min, respectively. We conclude that the viability of liver tissue begins to deteriorate after 1-1.5 h of ischemia. Using the level of adenosine triphosphate (ATP) as a parameter for viability, others had found this critical time period to be 1.5-2 h. Furthermore, we conclude that monitoring heat production of tissue provides a useful measure of viability for both clinical application and in connection with experimental liver surgery. PMID- 2315560 TI - Hepatic passage of bile acids increases oxygen uptake by perfused rat liver. AB - It has been claimed that the hepatic passage of conjugated bile acids does not increase oxygen uptake by the isolated perfused rat liver. We studied a variety of bile acids in the single-pass perfused rat liver. All bile acids studied except taurocholate and tauro-beta-muricholate induced an increase in oxygen uptake of 2.1%-11.2% (baseline 2.54 +/- 0.57 mumoles/min per g liver). Raised values for oxygen uptake were not specifically associated with the critical micellar concentration of the bile acid, with bile acid uptake, or with bile acid secretion. It is postulated that bile acid toxicity may have an intracellular effect on hepatic oxygen uptake. PMID- 2315562 TI - Acidification mechanisms. PMID- 2315561 TI - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Disease). PMID- 2315563 TI - Public health nurses' knowledge base and decision-making process in child health care: methodic experiment. PMID- 2315564 TI - Under what conditions do the gynaecologist/women, midwife/women meet at a gynaecological examination? PMID- 2315565 TI - Collaborative decision-making in nursing practice: a Norwegian study. PMID- 2315566 TI - Interaction between mother and infant. PMID- 2315567 TI - Effects of the training of integrity--promoting care on the interaction at a long term ward. Analysis of video-recorded social activities. AB - A training programme in integrity-promoting care was given the staff of a long term ward and practised during a three months intervention period. The effects were analysed in different parameters and compared with a control ward. This report describes analysis of video-recorded interactions (12 hs) during social activities between demented patients and caregivers and changes induced by the programme. The video-recorded episodes, containing mainly music and coffee sessions were interpreted from a model on interaction with demented patients suggested by Athlin & Norberg. The results indicate that the training programme and the guidance during the intervention resulted in increased understanding of demented patients' situation among the staff. They became more sensitive, adapted their cues and made the environment easier to interpret for the patients. This in turn led to the fact that the patients appeared more sensitive and clear in their cues. A positive circle developed. PMID- 2315568 TI - Errors of measurement affecting the reliability and validity of data acquired from self-assessed quality of life. AB - Research often uses self-assessed quality of life. Quality of life cannot be observed directly; other variables have to serve as its indicators. In the case of self-assessed quality of life, the researcher has to rely upon the individual's own statement as to how she/he feels. The subjective nature of the term creates problems in the matter of reliability and validity of the data thus collected. Random and systematic errors of measurement are liable to influence the result of the investigations. The researcher must know the possible sources of error and make allowances for them if research into quality of life is to be a worthwhile contribution to a greater understanding of what is meant by having a good life, and of the means to achieve it. PMID- 2315569 TI - Systematic and contextual caring science. A study of the basic motive of caring and context. PMID- 2315571 TI - Nursing as a scientific discipline. PMID- 2315572 TI - Quality of life--euthanasia. PMID- 2315570 TI - Urostomy appliances and stoma care routines. The relation to peristomal skin complications. AB - The aim of the study was to describe types of appliances and stoma care routines and evaluate their relation to peristomal skin complications. Sixty-six patients with a cutaneous uretero-ileostomy were interviewed and the peristomal skin was assessed according to Classification of Peristomal Skin (CPS). The results show a conservatism regarding the types of appliance and the stoma care routines. More than half of the patients used the same product at follow-up as they were initially fitted with three to 14 years earlier. The routines adopted by the patients were often inadequate, resulting in skin complications. Continuous exposure of the skin to urine by creation of a too wide opening in the face-plate and infrequent changing of the appliance resulted in development of pseudoverrucose skin lesions. PMID- 2315573 TI - [Esophageal manometry]. PMID- 2315574 TI - [Prevalence of superficial cutaneous mycoses in the Mosan region]. PMID- 2315575 TI - [Eosinophilic cellulitis (Wells' syndrome) and stings or bites by arthropods]. PMID- 2315576 TI - Adherence to sports injury rehabilitation programmes. AB - Many studies have shown that low adherence is a common problem in treatment programmes. Adherence to sports injury rehabilitation is dependent on the personality characteristics of athletes operating in conjunction with particular aspects of their rehabilitation settings and the quality of interactions developed between athletes and their therapists. Any attempt to view treatment adherence as a unitary construct is doomed to fail; a complex construct demands a multidimensional outlook. Taking into account the challenges that injured athletes face during their rehabilitation, strategies can be designed to promote adherence. Self-confidence is the key to enhanced rehabilitation adherence, and the strategies are organised within that framework. Competence strategies include education, treatment efficacy, tailoring, and relapse prevention training. Control strategies include dissociation, self-monitoring, decision-balance sheet, and pain deconditioning. Commitment strategies include shaping, contracting, threats, goal-setting, and social support. Because of the dearth of empirical data on the specific issue of adherence to sports injury rehabilitation programmes, it is necessary to extrapolate from various other areas of treatment adherence (e.g. cardiac rehabilitation). Treatment dropout does not seem to be inevitable, but is in fact preventable. The task for the sports medicine professional is to recognise and acknowledge the salient features of their clients and the rehabilitation demands on them and then to utilise various strategies to enhance the likelihood of treatment adherence. PMID- 2315578 TI - [What is your diagnosis? Baker's cyst with partially calcified detritus in chronic synovialitis chondrodetrica]. PMID- 2315577 TI - Femoral neck stress fractures. AB - Femoral neck stress fractures are unusual but not rare athletic injuries. In one large series they accounted for 5% of all stress fractures. Early recognition of the signs and symptoms of this injury is important, as objective findings are often delayed. The potential problems from this fracture are serious. The aetiology includes repeated force above a certain load without internal bone response time. Loss of shock absorption due to muscle fatigue and limitation of ankle motion by boots or splints may also play a role. The diagnosis is based on the finding of groin pain and radiographic testing, which often requires plain films and bone scintigraphy. Regular radiographic findings present in stages progressing from a normal film through sclerosis to a disruption of the cortex and displacement. Bone scintigraphy may be positive 2 or more weeks before plain film changes are present. Classification schemes follow the radiographic changes. A classification system and treatment plan may be based on 3 categories of these fractures--compression side, tension side and displaced femoral neck fracture. Treatment ranges from rest with early symptoms to surgical stabilisation for any widening of cortical cracks and/or displaced fractures. Prompt diagnosis and carefully supervised treatment is the key to preventing displacement. Prolonged disability secondary to pain, nonunion or avascular necrosis is associated with displacement of the femoral neck stress fracture. PMID- 2315579 TI - [Clinical presentation and diagnosis of coronary heart disease]. AB - Coronary artery disease may present as silent ischemia, chronic typical angina pectoris, unstable angina, Prinzmetal angina, acute myocardial infarction, and sudden cardiac death. These manifestations can usually be differentiated by the clinical history. Each of them has its own pathophysiology and, accordingly, therapy and prognosis are different. Myocardial ischemia is common to all of the manifestations and this can be assessed by history taking, ECG stress-testing, ambulatory monitoring, myocardial perfusion scanning, or radionuclide angiography (RNA). The diagnostic accuracy of these diagnostic procedures varies from 70% (history) to 81% (RNA). PMID- 2315580 TI - [Interventional therapy in coronary heart disease]. AB - The introduction of balloon angioplasty represents the major step in modern cardiology. Today four different techniques for interventional treatment of coronary artery disease are at our disposition for classic balloon angioplasty, laser balloon, catheter atheromectomy and endovascular prosthesis make interventions in coronary artery disease more easy and reliable. However, the main problem, restenosis, which appears in one fourth of the cases, is not yet resolved. We report our experience in 1000 cases of transluminal approach to coronary artery disease. PMID- 2315581 TI - [Postoperative mortality in surgery of cholelithiasis: a retrospective analysis from the years 1972-1980]. AB - In a retrospective study (1972-1980) we analyzed the postoperative mortality of 2916 consecutive cholecystectomies or interventions on the common bile ducts respectively. The mean age of the patients was 54 years (17-92 years), 63% were older than 60 years; 74% were women. We show that age, histology, intervention, stone localization, sex and concomitant internal diseases influenced the early postoperative mortality. The overall mortality was 0.7% (21 patients), 0.7% in the under 60 years old patients, 1.8% in the older aged group. The mortality in chronic cholecystitis was 0.5%, in acute cholecystitis 2.6%. After simple cholecystectomy we observed a mortality of 0.3%, after cholecystectomy and common bile duct intervention 2.5% (p less than 0.001), and after intervention on the common bile ducts 7.3%. Stones only in the gallbladder were associated with a mortality of 0.3%, cholecysto- and choledocholithiasis with 2.8% and choledocholithiasis alone with 7.3%. The mortality in men was significantly (p less than 0.001) higher as in women (1.2 against 0.6%). In 76% of the deceased we diagnosed preoperatively a concomitant internal disease. PMID- 2315582 TI - [Eyelid and ankle edema]. AB - A 57-year-old patient presented with periorbital and lower limb edema. The physical examination revealed no signs of cardiac insufficiency or chronic liver disease. Initial laboratory values showed significant hypoproteinemia and hyperlipidemia. Renal function was normal. Urinary protein excretion was 5.5 g/d. Thus, the patient was diagnosed to have nephrotic syndrome. The patient's history, the physical examination and further laboratory work-up suggested a primary glomerulopathy. Percutaneous renal biopsy was performed. The biopsy was diagnostic of minimal change glomerulonephritis. A therapy with steroids was initiated which induced a complete remission of the nephrotic syndrome. The patient has been relapse-free for the entire follow-up period. PMID- 2315583 TI - [A case from practice (164). Stage I Boeck's disease with recurrent uveitis, secondary glaucoma and erythema nodosa]. PMID- 2315584 TI - [A case from practice (164). Acute unilateral vestibular deficit on the left]. PMID- 2315585 TI - [What is your diagnosis? Chronic paroxysmal hemicrania]. PMID- 2315586 TI - [Psychodynamic and general psychotherapeutic aspects of the treatment of depressive patients]. AB - Successful approach to depressed patients demands some knowledge of psychodynamic mechanisms in depressive patients according to a basic understanding of depression as a biological and a psychological disorder. Departing from such a point of view some important aspects of understanding and coping with depressives are the following: 1. Therapy of the depressed means communication. 2. Because of a deficiency in the development of emotions and self-esteem in childhood and youth depressives have a tendency to need very close symbiotic relationships and also tend to develop high standards in work efficiency and ethic norms. 3. Closeness and empathy, benevolence as well as patience and interest in the patient import and demand communicative partnership, valuation of collaborative efforts and form the basis of a therapeutic relationship. 4. Dangers lie in playing down and thus depreciation or in overdramatization. 5. Prolonged work with depressed patients requires supervision, acquisition of psychosocial competence and collaboration in Balint-groups. PMID- 2315587 TI - [A pilot test of the efficacy of a povidone-iodine-based surgical soap]. AB - A PVP-iodine containing surgical soap (low-iodine) was tested by 20 volunteers (14 women and 6 men) under conditions usually present in surgical clinics. The results proved the efficacy of this soap, as its usage entails a significant decrease in the number of germs. Two of the volunteers presented diverging results. The results of that study, confirmed by other studies, are interpreted and discussed. PMID- 2315588 TI - [Paradoxical aspects of neurotic behavior]. AB - Neurotic splitting of the human personality can be viewed as a form of maldevelopment of the brain which is split organically and functionally in several ways, thus harboring in part unreasonable contradictions. The latter surface in contrasts such as: consciousness versus unconsciousness, body versus soul, word versus sentiment. Limits towards neurotic diseases are difficult to define. They challenge the therapist to gently abandon his conventional role and to find--sometimes paradoxical--language for his clients. PMID- 2315589 TI - [Vysorel/Isorel--cancer drug from Viscum album. Documentation No.20]. AB - Vysorel/Isorel is an aqueous extract from fresh mistletoe (viscum album). A number of components with different possible effects have been isolated, but exact analyses of the preparation have not been published. One ampoule 'Starke 60' of 1 ml contains the extract of 60 mg mistletoe. Vysorel/Isorel is recommended in all malignant diseases, in 'precancerous' conditions and for prevention of relapse. Vysorel/Isorel is supposed to be taken subcutaneously according to a rhythmic schedule. Drug costs for one year in precancerous conditions are approximately 900 DM, for prevention of recurrence approximately 1800 DM, in the case of inoperable tumour approximately 3800 DM. Vysorel/Isorel is also a product of the anthroposophical medicine according to R. Steiner. It is marketed by Novipharm GmbH as Isorel in Austria and as Vysorel in the Federal Republic of Germany. The clinical efficacy of Vysorel/Isorel is derived from the demonstration of proteins from mistletoe (so-called 'Vester's Protein') with cancerostatic activity in vitro. No preclinical or clinical investigations are available. None of the 33 case histories suggests that Vysorel/Isorel is effective in the treatment of malignant diseases. Vysorel/Isorel is not registered in Switzerland at the IKS. It has been permitted in Austria since 1983 and in Germany since 1986. PMID- 2315590 TI - [Heart contusion]. AB - This 40 year old patient was involved in a car accident which resulted in a thoracic trauma with fracture of the sternum and the left radius. The ECG showed a complete right bundle branch block and a left anterior fascicular block (= bifascicular block). These electrocardiographic findings and an elevated CK-MB fraction after thoracic trauma were indicative for the diagnosis of myocardial contusion. The ECG was normal after 24 hours, the CK-MB after two days. The patient left the hospital after one week. Five weeks later, a control examination showed no cardiological abnormalities. PMID- 2315591 TI - [A case from practice (166). Mycoplasma pneumonia]. PMID- 2315592 TI - [A case from practice (167). Decreased glucose tolerance with reactive postprandial hypoglycemia in obesity]. PMID- 2315593 TI - [The effect of nutritional energy intake on endurance]. PMID- 2315594 TI - [The injured muscle (overexertion or acute injury): definitions, study methods and therapeutic proposals]. PMID- 2315596 TI - [Consultations for infants in an infant-juvenile psychiatric service. Catamnestic study based on 28 cases. Evaluation of therapeutic interventions performed and results obtained as a function of the family psychodynamic organization]. PMID- 2315595 TI - [Tendon pathology in athletes]. PMID- 2315597 TI - [Liaison psychiatry: a triangular model]. PMID- 2315599 TI - [AIDS: the moral of a story]. PMID- 2315598 TI - [Comparison of 2 antitussive agents in pediatrics (butamirate citrate in drinkable solution and zipeprol syrup)]. PMID- 2315601 TI - The journal as a forum for unsettled questions. PMID- 2315600 TI - Thymoma. AB - A review of the evaluation, treatment, and end results for 52 patients with thymoma treated at The University of Texas M.D. Anderson Cancer Center (1950 1984) is presented. The objective of the study was to examine the influence of a number of clinical characteristics on survival, including histologic and staging classifications, associated diseases, symptom status, and treatment. Forty-nine patients (94%) underwent surgical exploration; 13 were stage I, 12 were stage II, and 24 were stage III. Complete resection was accomplished in all of the stage I and II groups and in 6 of the stage III patients. An asymptomatic history, surgical stage I disease, lymphocytic thymoma cell type, and complete resection favorably influenced prognosis. The cumulative 5-year survival rate for all patients was 40%. No patient with stage I thymoma had recurrent disease, however, there were 9 recurrences (50%) in the completely resected stage II/III patients, six of whom remained disease-free following treatment with radiotherapy, chemotherapy, or a combined approach. PMID- 2315602 TI - To err is human. PMID- 2315603 TI - Women's rights and the medical use of fetal tissue: an international perspective. PMID- 2315604 TI - Under your calvarium. Brown University Program in Medicine 1989 commencement speech. PMID- 2315605 TI - Absence of correlations between indices of systemic inflammation and synovial fluid interleukin 1 (alpha and beta) in rheumatic diseases. AB - There are two forms of the cytokine interleukin 1 (IL1), produced by two distinct genes encoding a neutral (IL1 beta) and an acidic (IL1 alpha) peptide. They have powerful pro-inflammatory, immunopotentiating, catabolic and arthritogenic properties in vivo and have been implicated in the pathogenesis of rheumatic diseases. In this study, using specific immunoassays, we have measured both IL1 alpha and IL1 beta levels in synovial fluids (SF) from a large number of patients with different rheumatic diseases. Biologically significant levels of both cytokines were found in SF from patients with different forms of arthritis, but no correlations were found with any of the measures of disease activity that we tested. We also describe the presence in joint exudates of biological inhibitor(s) that neutralize IL1-induced T-cell activation. This is the first report of IL1 alpha and IL1 beta measurements in the same synovial exudates and also of the comparison of local levels of these cytokines with conventional indices of systemic inflammation. PMID- 2315607 TI - Type IV collagen and laminin in the synovial intimal layer: an immunohistochemical study. AB - The distribution of type IV collagen and laminin in the intimal layer of rheumatoid, osteoarthritic, traumatic and normal human synovium was determined by immunohistochemistry using polyclonal and monoclonal antibodies. All samples showed a similar pattern of labelling with type IV collagen and laminin present around the synovial intimal cells. Type IV collagen has previously only been identified in association with basement membranes which are not found at this site. Two major basement membrane components around synovial cells suggest the formation of a modified basement membrane-like structure. PMID- 2315606 TI - Intraarticular corticosteroid injection into rheumatoid arthritis knees improves extensor muscles strength. AB - Eleven arthritic knee joints in seven patients with rheumatoid arthritis were studied before and after intraarticular injection of a corticosteroid preparation. Extensor muscle torque and quantitative electromyography increased on days 7 and 14 after treatment, indicating that muscle function had been inhibited by synovitis. Clinical signs of synovitis, such as pain, range of motion and knee circumference, also improved. Synovial fluid withdrawal alone improved extensor muscle torque. Joints with instability and/or radiological cartilage involvement also improved. PMID- 2315609 TI - A link between HIV infection and circumcision. PMID- 2315608 TI - Bisphosphonates in collagen arthritis. AB - Bisphosphonates suppress bone destruction in various diseases. We studied the effects of 3-amino-hydroxypropylidene-1,1-bisphosphonate (APD), and dimethyl-APD in the collagen model of chronic arthritis in rats. The incidence and severity of arthritis was not lower in rats treated with APD or dimethyl-APD compared with controls. The cellular and humoral immune responses to collagen were also similar in the treated and untreated animals. In all animal groups the same bone destruction was found radiographically 42 days after immunization. This study demonstrates that bisphosphonates do not suppress the course of collagen arthritis in rats. PMID- 2315610 TI - How to land the job you want. PMID- 2315611 TI - It's never just a miscarriage. PMID- 2315612 TI - Learning to conduct research--the hard way. PMID- 2315613 TI - Research really can pay off. PMID- 2315614 TI - What's wrong with this patient? PMID- 2315616 TI - The pain of codependence. PMID- 2315615 TI - Nurses are the key to quality health care. PMID- 2315617 TI - The smaller the patient, the bigger the risk. PMID- 2315618 TI - New answers to "how much should I weigh?". PMID- 2315619 TI - An rx for building professional pride. PMID- 2315620 TI - Education expenses: a payoff at tax time. PMID- 2315621 TI - Group support builds patient morale. PMID- 2315622 TI - When the solution is a prosthesis. PMID- 2315623 TI - AIDS dementia. Your assessment can make all the difference. PMID- 2315624 TI - Don't underestimate the lumpectomy patient's needs. PMID- 2315625 TI - New drugs you're giving now. PMID- 2315626 TI - In support of premarital HIV testing. PMID- 2315627 TI - For a child with pneumonia, there's no place like home. PMID- 2315628 TI - Health in the 1990's. PMID- 2315629 TI - A conversation about new directions for health care. PMID- 2315630 TI - New directions for health care: what can we expect? PMID- 2315631 TI - Managing your money: choosing your investments. PMID- 2315632 TI - What is nursing? PMID- 2315633 TI - Pronouncing and certifying death. PMID- 2315634 TI - Getting louder on nurses' job action. PMID- 2315635 TI - [Effect of the geometry of atherosclerotic carotid artery lesions on their angiography image--an arteriography study]. AB - Atherosclerotic lesions of the carotid arteries are frequently located eccentrically and are of asymmetric configuration. For their angiographic detection at least two orthogonal views are mandatory. The carotid bifurcations, the proximal internal carotid artery and the carotid siphon can be visualised free from vessel overlap only via often mandatory lateral views that must be obtained by selective arteriography (IA DSA). Smaller lesions and ulcerations of the carotid bifurcation area may be misinterpreted with nonselective IA DSA and IV DSA because of their geometry. PMID- 2315636 TI - [Quality criteria for intra-oral roentgen images]. AB - The apical and marginal parodontium are the main targets in dental roentgenology. The most important structural details are of 0.1 to 1.0 mm size. Their imaging is determined by - among other parameters - The X-ray film technique. This article presents quality criteria for a number of standard projections, that appear suitable for assessing the image quality. Other factors determining the characteristics of an x-ray film have been neglected, the only exception being a short treatise on the importance of contrast. PMID- 2315637 TI - Urography with spasmolytics. AB - The effects of glucagon (1 mg i.v.) and hyoscine butylbromide (Buscopan 20 mg i.v.) and placebo on the visualization of the pyelocalyceal systems and ureters was compared in a routine urography with abdominal compression in a double-blind, randomized trial comprising 189 kidneys and ureters. The visualization of the ureters in the supine position was highly significantly better than in the prone. In the prone position the ureteral visualization with Buscopan was marginally significantly better than with placebo or glucagon. Otherwise, neither Buscopan nor glucagon improved the pyeloureteral visualization. However, with glucagon the pyelocalyceal visualization was highly significantly poorer than with placebo, and marginally significantly poorer than with Buscopan. PMID- 2315638 TI - [Ectopia of the right ureter as the cause of a cystic abdominal space-occupying lesion]. AB - Ureteral ectopias, which mostly occur in ureteral duplications, become noticeable in women quite early by characteristic clinical signs (dribble, or urinary incontinence). In males, it is usually only a stenosis-conditioned dilatation of the ureter that results in an uncharacter-istic pattern of complaints. The article presents the clinical pattern of signs and the x-ray findings in a man of 42 year of age, who had not reported any complaints until then, with an excessive dilatation of an extopically discharging single ureter. PMID- 2315639 TI - [Methodologic procedure in the removal of a knotted intravascular pulmonary artery catheter]. AB - Distal knotting of a pulmonary artery catheter that had been introduced via the subclavian or jugular vein, is a possible complication. To avoid venous dissection in the thoracic or cervical regions, removal via a transfemoral approach should be considered as a feasible alternative. The article report on the extraction of two knotted pulmonary artery catheters, effected transfemorally. PMID- 2315640 TI - [Pulmonary cryptococcosis--a rare differential diagnosis of intrapulmonary coin lesions]. AB - In connection with a case of pulmonary cryptococcosis, the clinical manifestations, radiological findings and therapeutic possibilities are discussed. Although pulmonary cryptococcosis is relatively uncommon, the diagnosis should be considered in any immunologically compromised patient with an abnormal chest roentgenogram. PMID- 2315641 TI - Structure of the normal liver sections in microangiographic studies and CT scanning. AB - Based upon the results of microangiographic (MAR) and computed tomography (CT) studies of thin slices of the normal liver preparations the author reveals subtle morphological structures of the liver, namely, terminal branches of the portal vein and lobular sinusoids shown in MAR examinations, and hepatic laminae arranged in the so-called muralium simplex visualized in CT scanning. PMID- 2315642 TI - [Magnetic resonance tomography of adrenoleukodystrophy]. AB - Adrenoleucodystrophy (ALD) is an uncommon, sex-linked disease, characterised by the accumulation of very long-chain fatty acids in various tissues. There is a great predilection for young boys between the age of three and ten years. The disease ends fatally after a clinical course of several years. The clinical and MR findings of a child with typical ALD are presented. T2-weighted MR demonstrates confluent, symmetrical, hyperintense lesions of the occipital white matter bilaterally. After the application of Gd-DTPA, contrast enhancement is seen in the margins of the lesions indicating active demyelination. MR is recommended as imaging modality of choice in patients with suspected or confirmed diagnosis of adrenoleucodystrophy. PMID- 2315643 TI - Anorexia nervosa and zinc. PMID- 2315644 TI - A method for determination of normal or abnormal blood volume in patients subjected to radionuclide cardiography. AB - The blood volume can be measured after labelling of red blood cells with technetium-99m. In addition, the blood volume and its standard error of estimate can be calculated from the subject's sex, height and deviation from desired weight. By comparing the measured blood volume with the estimated normal blood volume and using a statistical test, it can be decided whether a measured blood volume is normal or not. This method was applied to a group of 36 patients with heart diseases. Four of the patients had abnormal blood volumes. In the remaining 32 patients the measured blood volumes were equally distributed around the estimated mean normal values. The method described for determination of normal/abnormal blood volumes can be considered a by-product of routine radionuclide cardiography. PMID- 2315645 TI - Lipid peroxidation and antioxidant supplementation in old age. AB - An age-related rise in blood lipid peroxides measured by the thiobarbituric acid (TBA) method has been reported in several studies. Our study was designed to investigate whether this could be attributed to antioxidant deficiencies in aged individuals. We therefore measured the TBA-value of young and old women and related this to vitamin E and selenium status and the fatty acid composition, triglyceride and cholesterol content of platelet-poor plasma. A significant difference (p less than 0.001) between young and old women in the plasma TBA value and the plasma lipid parameters was found. Old women had a lower selenium status than the young women (p less than 0.01), but their vitamin E status was fully adequate. Only the lipid parameters correlated significantly (p less than 0.001) with the TBA-value. In a 3-month placebo-controlled supplementation trial with vitamin E and selenium, the plasma TBA-value of the old women did not change. This study shows that the TBA-value of plasma is primarily determined by the fatty acid content and is not influenced by antioxidant supplementation in healthy individuals. The question of the sensitivity of the TBA-test is discussed. PMID- 2315646 TI - Serum ferritin and iron status in a population of 'healthy' 85-year-old individuals. AB - Iron status, including S-ferritin, S-iron, S-total iron binding capacity (TIBC), TIBC saturation, haemoglobin (Hb) and dietary iron intake, was assessed in a population study comprising 92 healthy 85-year-old subjects (32 males, 60 females). S-iron, S-TIBC, TIBC saturation and S-ferritin values were not significantly different in the two sexes. Males had a geometric mean S-ferritin of 130 micrograms/l, females of 98 micrograms/l. Ferritin levels less than 15 micrograms/l (i.e. depleted iron stores) were found in one female (1.6%); and in one male (3.1%), who in addition had iron deficiency anaemia. None of the females displayed latent iron deficiency (i.e. S-ferritin less than 15 micrograms/l and S TIBC saturation less than 15%) or iron deficiency anaemia. Arithmetic mean Hb was 145 +/- 13 (SD) g/l (9.0 +/- 0.8 mmol/l) in males and 139 +/- 11 g/l (8.6 +/- 0.7 mmol/l) in females (p less than 0.02). Median nutritional iron intake was 10 mg/day (range 3-17), higher in males (median 12) than in females (median 9) (p less than 0.0001). Iron intake showed significant correlations to S-iron, S-TIBC and TIBC saturation, but not to S-ferritin. PMID- 2315647 TI - The amino terminal portion of cerebrospinal fluid cystatin C in hereditary cystatin C amyloid angiopathy is not truncated: direct sequence analysis from agarose gel electropherograms. AB - The isolated amyloid substance in hereditary cystatin C amyloid angiopathy (HCCAA) is mainly composed of a cystatin C variant devoid of the 10 amino terminal amino acid residues of extracellular cystatin C from healthy individuals. We have developed a procedure for protein sequencing directly from agarose gel electropherograms and used this in conjunction with isoelectric focusing to investigate the amino terminal sequence of cerebrospinal fluid (CSF) cystatin C in HCCAA patients. The amino-terminal sequence determined for cystatin C from a HCCAA patient CSF sample, Xaa-Ser-Pro-Gly-Lys-Pro-Pro-Xaa-Leu-Val-Gly Gly-Pro-Met-Xaa-Ala-Xaa-Val, showed that the protein was not amino-terminally truncated. CSF cystatin C from all nine HCCAA patients investigated was found to have an isoelectric point identical to that of native cystatin C, and the truncated form of cystatin C isolated from amyloid deposits was shown to contribute to less than 1% of the total amount of cystatin C in CSF. The total cysteine proteinase inhibitory capacity of CSF from HCCAA patients was lower than that of CSF from other patients. This decreased CSF inhibitory capacity in HCCAA patients was caused by decreased levels of cystatin C, since the levels of the other two cysteine proteinase inhibitors found in CSF, alpha 2-macroglobulin and kininogen, were significantly higher than in CSF from non-HCCAA patients. PMID- 2315648 TI - Functional capacity of neutrophil granulocytes in deep-sea divers. AB - Neutrophil granulocytes (PMN) are main defenders against invading microbes. We evaluated the adaptive response of PMN from divers exposed for weeks to high total and oxygen pressures. Under these conditions PMN could be primed to give a heightened respiratory burst upon stimulation with the bacterial peptide analogue, formyl-methionyl-leucyl-phenylalanine (FMLP): blood PMN sampled both shortly after operational saturation dives offshore and during an onshore test dive gave larger responses than control pre- or post-dive PMN from the same subjects and PMN from laboratory personnel. The assays used measured oxygen consumption, intracellular H2O2 availability, and chemiluminescence. The submaximal responses provoked by the non-metabolizable diacylglycerol analogue phorbol myristate acetate (PMA) were less and less often increased. Such enhanced PMN responsiveness may possibly decrease resistance to skin and other infections that are encountered in divers, if PMN thereby failed to localize correctly to inflamed tissues. PMID- 2315649 TI - Guidelines for description of immunoassay kits. AB - A provisional recommendation in order to improve manufacturers' and marketers' information to users of immunoassay kits has been compiled by a Nordic Clinical Chemistry project working group. PMID- 2315650 TI - Recommendation for collection of venous blood from children, with special reference to production reference values. AB - Reference values should be produced under standardized conditions. To enable comparison it is desirable to use the same procedure also in other clinical situations. A procedure for the collection of venous blood from children with special reference to production of reference values is recommended. It deals with five items: preparation of the child before specimen collection, preparation of the blood collection site, equipment for specimen collection, the specimen collection itself, and handling and storage of the specimen. Alternative methods are described since no single method is suitable for all paediatric age groups. The problem of adhering to a proposed procedure during routine clinical work is also commented upon. The recommendation has been produced as a joint effort of the Scandinavian Committee on Reference Values and a working group set up by the National Paediatric Societies in the Nordic countries. PMID- 2315652 TI - [Ergometric assessment of functional performance deficit in psychosomatic patients]. AB - Patients with marked loss of physical and psychological fitness and cardiovascular symptoms without objective findings often pose diagnostic problems. Fifteen patients hospitalized for general incapacity with normal cardiovascular findings were tested in the ECG laboratory on a conventional bicycle ergometer and in a more natural environment climbing stairs in a windowed staircase. Work capacity in the two tests was compared. Eight out of fifteen patients achieved only 40% of their age and weight adjusted nominal value on the bicycle ergometer, while they were fully efficient on the staircase (= discordant result). Four patients reached their expected nominal values in both tests. The performance of three patients was much lower than expected, more markedly so in the laboratory situation on the bicycle. All patients' performance was limited by central nervous incapacitating cardiovascular symptoms. Diagnosis of psychosomatic situational cardiovascular insufficiency in the absence of pathological findings can be substantiated by comparing exercise tests in a physiological and non-physiological environment. This is helpful to both patient and physician by facilitating a more precise diagnostic process and documentation of therapeutic improvement. PMID- 2315651 TI - [364 anonymous screening tests for AIDS at the Vaudois University Hospital Center: who? why?]. AB - From 1 July to 31 December 1988 risk factors for HIV infection were systematically recorded for all individuals tested anonymously at our institution and compared with similar data observed when anonymous testing was introduced (1985-1986). The absolute number of homosexuals and intravenous drug abusers remained stable but their ratio decreased because most tests are now performed in persons with multiple heterosexual partners. More than half of heterosexuals said they used condoms. Tests were positive only in homosexuals and intravenous drug abusers. These data suggest that the ongoing Swiss nationwide educational programmes have been successful in reaching people potentially exposed to HIV. Such campaigns may still prevent the dissemination of HIV infection to the heterosexual population. PMID- 2315653 TI - [Several years observation of a Catergen (cyanidanol-3) induced immunohemolysis]. AB - A report is presented on repeated severe episodes of cyanidanol-induced immune hemolysis in a 75-year-old woman suffering from chronic active hepatitis. One year after the first hemolytic episode, high titers of anticyanidanol antibodies were still demonstrated in the patient's serum (as well as sensitization of the patient's lymphocytes by the drug). 4 years later virtually no decrease of the antibody titer was found. Further investigations of the patient's serum revealed antibodies against flavonoids with free hydroxyl groups (cyanidanol and rutin). However, no antibodies against flavonoids with derivatized hydroxyl groups (troxerutin, mixture of hydroxy-ethyl-rutin and silibinin) could be demonstrated. Sensitization with flavonoids other than cyanidanol preceding cyanidanol-induced hemolysis has been proposed by others. In this case storage of approximately 75 flavonoid containing preparations in a chemist's shop in the patient's house may have contributed to the astonishing persistence of dry dependent antibodies. PMID- 2315654 TI - [Exertion-induced lactic acidosis in celiac artery stenosis]. AB - A well-trained young male developed effort-induced dyspnea due to marked lactic acidosis. In the absence of cardiopulmonary problems, enzyme defects, primary hepatopathy or myopathy, abdominal angiography revealed subtotal stenosis, and duplex sonography (15 years later) total occlusion, of the celiac trunk associated with hepatic steal syndrome. We suggest that the marked, effort induced lactic acidosis may be a metabolic consequence of Dunbar syndrome (stenosis of the celiac trunk due to compression by the crura diaphragmatica). PMID- 2315655 TI - [Calcium carbonate for the treatment of hyperphosphatemia in chronic hemodialysis patients]. AB - Hyperphosphatemia in chronic hemodialysis patients is usually treated with aluminium containing phosphate binders. In recent years there has been increasing evidence of serious complications due to aluminium accumulation. We have investigated a new calcium carbonate preparation with an HCl-resistant capsule designed to prevent gastrointestinal side effects. Its phosphate binding capacity in comparison to aluminium chloride hydroxide was investigated in 17 chronic hemodialysis patients. The dose of the phosphate binder was adjusted regularly so that the serum phosphorus levels were below 1.8 mmol/l. The mean dose of aluminium chloride hydroxide was 3.36 g/day and of calcium carbonate 4.96 g/day. The mean (+/- SD) serum calcium level was 2.58 +/- 0.11 mmol/l under aluminium chloride hydroxide and 2.50 +/- 0.25 mmol/l under calcium carbonate. The mean phosphorus level was 1.69 +/- 0.31 mmol/l under aluminium chloride hydroxide and 1.71 +/- 0.33 under calcium carbonate. Serum aluminium fell from 64.5 +/- 14.4 micrograms/l to 28.5 +/- 17.5 micrograms/l after 3 months. PMID- 2315656 TI - [Hereditary chondrocalcinosis in Switzerland: a new family]. PMID- 2315657 TI - [Soft-tissue profile changes through therapy with the Herbst hinge appliance]. AB - The posttreatment tissue profile changes that can be observed after treatment with the Herbst therapy were investigated in a class II malocclusion mixed dentition group. Profile photographs of two groups of 18 patients were compared. One group was treated with the Herbst appliance, the other served as an untreated control. The treated cases were retained by means of an activator after the active treatment period. After this retention period, new profile photographs were taken and compared to the controls. All treated patients displayed a significant improvement of the soft tissue profile at the end of the active treatment period. After retention a relapse tendency could be observed. Due to the large range of observed treatment effects, no correlation between soft tissue profile and skeletal changes could be found. PMID- 2315658 TI - Local differences in the newly formed crevicular microbiota. AB - Subgingival plaque samples were taken from upper and lower right canines, premolars, and first molars (distal, mid-buccal and lingual) in 10 periodontally healthy individuals after four days without oral hygiene. The samples were examined in the darkfield microscope. Counts and proportions of morphotypes were related to the location of the sampled sites. The influence of site location on the distribution of morphotypes was studied by multiple regression analysis. Inter-individual differences were significant for the proportions of cocci, nonmotile rods and fusiform organisms (p less than 0.001), the influence of site location was not. Significant differences (p less than 0.05) were found between total bacterial counts of samples taken from different sites: Distal-buccal samples contained more bacteria than did mid-buccal samples, mid-buccal ones contained more than lingual samples; samples from more posterior teeth contained more bacteria. The experiment was repeated after 5 weeks. The intertest agreement (kappa) for the presence of the different morphotypes ranged between 0.13 and 0.30. Coefficients of variation of the proportions of morphotypes determined in repeated samples were between 1.35 and 3.13. PMID- 2315659 TI - [Bristle end rounding and anchoring in children's toothbrushes]. AB - This scanning electron microscopic study of eight toothbrushes for children has shown differences in quality and quantity of the rounding of bristle ends. While four products which were examined for the first time were partially deficient, the preparation of the other toothbrushes had clearly improved in comparison to previous products. Quotas of acceptable end rounding of the bristles varied considerably between 14.3% and 90.2%. Welding of bristle bundles at their base into the head of the toothbrush offers hygienic advantages. PMID- 2315660 TI - [Autotransplantation and orthodontic planning]. PMID- 2315662 TI - [The moment-of-force and -rotation ratio]. PMID- 2315661 TI - [Orthodontics: the absence of tooth primordium: treatment planning of malocclusions with partial anodontia]. PMID- 2315663 TI - [Questions about deciduous tooth eruption]. PMID- 2315664 TI - [Orthodontics--its current status. Interview by Kurt Venner]. PMID- 2315665 TI - Unconscious mental functioning. PMID- 2315666 TI - Test negative. A look at the "evidence" justifying illicit-drug tests. PMID- 2315667 TI - Who's the dealer? What controls gene shuffling in the immune system? PMID- 2315668 TI - Smelling better. Smell-blindness "cure" may point to olfactory mechanism. PMID- 2315669 TI - Fallout. New radiation-risk estimates prompt calls for tighter controls. PMID- 2315670 TI - Safe passage? Study fuels debate over safety of birth centers. PMID- 2315671 TI - Interleukin-2. PMID- 2315672 TI - Likely litigation. Companies wield lawsuits as a market-development tool. PMID- 2315674 TI - Science behind the Wall. East Germany's liberated scientists regroup. PMID- 2315673 TI - Right to lie? Studies disprove claims about abortion's dangers. PMID- 2315676 TI - Net result: folded protein. A neural network deciphers the structure of protein. PMID- 2315675 TI - All about Eve. Did the mother of us all live less than 200,000 years ago? PMID- 2315677 TI - Space invaders. Extra! Extra! Flu linked to sunspots! PMID- 2315678 TI - Tone of relief. Ultrasound speeds the release of drugs from medical implants. PMID- 2315679 TI - The unusual origin of the polymerase chain reaction. PMID- 2315680 TI - Of mice and men. How form affects function in monoclonal-antibody drugs. PMID- 2315681 TI - The use of central venous catheters in paediatric oncology--a cautionary tale. AB - The use of indwelling central venous catheters has become widespread since their introduction by Broviac et al in 1973 and Hickman et al in 1974. They are of particular value in paediatric oncology where young children require intensive chemotherapy over a long period of time and where peripheral venous access may become a problem. PMID- 2315682 TI - Influence of anaesthesia on blood loss in transurethral prostatectomy. AB - In this study operative blood loss was measured in 177 transurethral prostatectomies performed over a six-year period in one hospital by the author. A comparison was made relative to type of anaesthesia used i.e. general inhalation versus spinal anaesthesia. The two groups were similar in age and physical condition. Their prostates were almost the same size and there was negligible difference in the rate of resection between the two groups. Mean loss and median loss in 113 patients given general anaesthesia were 66.6 and 29.9 ml. In 64 patients who had spinal anaesthesia these losses were 35.6 and 22.2 ml respectively. The findings are in agreement with two of the three previous studies devoted to the relationship between operative blood loss during transurethral prostatectomy and the type of anaesthesia used. PMID- 2315683 TI - Urethral valves--treatment, results and urodynamic assessment. AB - Posterior urethral valves is an uncommon condition, but it poses many diagnostic and therapeutic problems. Long term follow up of these patients revealed that the majority of these boys have long term problems. In depth assessment of 10 boys with this problem revealed that their upper urinary tracts remained stable whereas urodynamic studies showed gross micturition abnormalities. Most methods of assessing the urinary tracts in these boys are invasive (eg. Intravenous urography, micturating cystography) and may indeed show no change in upper tract radiology despite marked abnormalities of micturition detected by urodynamics and which may require further investigation and treatment. We therefore recommend regular urodynamic assessment of these boys as it is accurate and initially non invasive. Those boys with a detectable abnormality can progress to further studies. PMID- 2315684 TI - Multiple gastric carcinoid tumours associated with atrophic gastritis. AB - A case of multiple gastric carcinoid tumours is described in an elderly man with atrophic gastritis and hypergastrinaemia. This case provides further evidence of an association between hypochlorrhydric states and some gastric endocrine tumours. PMID- 2315685 TI - Thyrotropin receptor antibodies associated with post-operative relapse of thyrotoxicosis in a pregnancy complicated by neonatal thyrotoxicosis. AB - This case describes the clinical, biochemical and immunological features associated with relapse of thyrotoxicosis during pregnancy in a patient who had recently undergone a subtotal thyroidectomy for Graves' disease. The baby, shortly after birth, showed clinical and biochemical features of thyrotoxicosis which responded to carbimazole therapy. Thyrotropin receptor antibodies and thyroid stimulating antibodies were present in the blood of the mother and baby. The clinical course of the neonatal thyrotoxicosis correlated with the TSH receptor antibody levels. PMID- 2315686 TI - Guillain-Barre syndrome and pan-uveitis. AB - A case history of a patient diagnosed as having Guillain-Barre syndrome who is also found to have a pan-uveitis which has caused significant deterioration in vision and which has been slow to resolve on treatment. This would appear to be the first such report in the literature. PMID- 2315688 TI - Low-dose radiation exposure. PMID- 2315689 TI - Academy panel raises radiation risk estimates. PMID- 2315687 TI - Coexistent coronary artery disease and oesophageal spasm: the importance of establishing the source of chest pain. AB - A 55 year old woman presenting with chest pain was found to have significant triple vessel coronary artery disease. Non-invasive investigations showed that she had a good exercise tolerance without inducible ischaemia. The history was more suggestive of an oesophageal source of pain, an impression supported by manometry. This case illustrates some of the problems encountered during the investigation of chest pain and the need to interpret angiographic findings in the context of the patient's functional state. PMID- 2315690 TI - Getting to the heart of the cholesterol debate. PMID- 2315691 TI - Risk assessors taken to task. PMID- 2315692 TI - NIH seeks a chief, desperately. PMID- 2315693 TI - Gene therapy proposed. PMID- 2315694 TI - Conserved residues make similar contacts in two repressor-operator complexes. AB - Comparison of a lambda repressor-operator complex and a 434 repressor-operator complex reveals that three conserved residues in the helix-turn-helix (HTH) region make similar contacts in each of the crystallographically determined structures. These conserved residues and their interactions with phosphodiester oxygens help establish a frame of reference within which other HTH residues make contacts that are critical for site-specific recognition. Such "positioning contacts" may be important conserved features within families of HTH proteins. In contrast, the structural comparisons appear to rule out any simple "recognition code" at the level of detailed side chain-base pair interactions. PMID- 2315696 TI - Gene therapy clears first hurdle. PMID- 2315697 TI - Heart like a wheel. PMID- 2315695 TI - The direction of membrane lipid flow in locomoting polymorphonuclear leukocytes. AB - The objective of this study was to determine the direction of membrane lipid flow in locomoting cells. The plasma membrane of human polymorphonuclear leukocytes was stained with a fluorescent lipid analog dihexadecanoyl indocarbocyanine. A line was photobleached on the cell surface perpendicular to the direction of cell motion. Low-light-level fluorescence microscopy and digital image-processing techniques were used to analyze a series of images taken at short intervals after photobleaching. The bleached line remained visible for about 5 seconds before being erased by diffusional recovery. Examination of fluorescence intensity profiles allowed a comparison to be made between the velocities of line and cell movement. Results indicate that the bleached line moves forward with the same velocity as the cell during locomotion, refuting the retrograde lipid flow model of locomotion. Instead, the plasma membrane lipid appears to move forward according to either the unit movement of membrane or the tank track model of locomotion. PMID- 2315698 TI - CF screening delayed for awhile, perhaps forever. PMID- 2315699 TI - Deciphering the message in protein sequences: tolerance to amino acid substitutions. AB - An amino acid sequence encodes a message that determines the shape and function of a protein. This message is highly degenerate in that many different sequences can code for proteins with essentially the same structure and activity. Comparison of different sequences with similar messages can reveal key features of the code and improve understanding of how a protein folds and how it performs its function. PMID- 2315700 TI - Requirement for activin A and transforming growth factor--beta 1 pro-regions in homodimer assembly. AB - Many proteins are initially synthesized as part of a large precursor. The role of the pro-region in the biosynthesis of transforming growth factor--beta 1 (TGF beta 1) and activin A, two structurally related disulfide-linked homodimers synthesized as large precursors, was studied. Vectors that expressed either the pro-region or the mature regions of these molecules were used in complementation experiments, only when the pro-region was coexpressed with the mature region did intracellular dimerization and secretion of biologically active homodimers occur. The pro-regions of activin A and TGF-beta 1, therefore, aid the folding, disulfide bond formation, and export of their respective homodimers. PMID- 2315701 TI - Molecular cloning of the Bombyx mori prothoracicotropic hormone. AB - Prothoracicotropic hormone (PTTH), a brain secretory polypeptide of insects, stimulates the prothoracic glands to produce and release ecdysone, the steroid essential to insect development. The complementary DNAs encoding PTTH of the silkmoth Bombyx mori were cloned and characterized, and the complete amino acid sequence was deduced. The data indicated that PTTH is first synthesized as a 224 amino acid polypeptide precursor containing three proteolytic cleavage signals. The carboxyl-terminal component (109 amino acids) that follows the last cleavage signal represents one PTTH subunit. Two PTTH subunits are linked together by disulfide bonds, before or after cleavage from prepro-PTTH, to form a homodimeric PTTH. When introduced into Escherichia coli cells, the complementary DNA directed the expression of an active substance that was functionally indistinguishable from natural PTTH. In situ hybridization showed the localization of the prepro PTTH mRNA to two dorsolateral neurosecretory cells of the Bombyx brain. PMID- 2315702 TI - Simulation of paleocortex performs hierarchical clustering. AB - Simulations were performed of layers I and II of olfactory paleocortex, as connected to its primary input structure, olfactory bulb. Induction of synaptic long-term potentiation by means of repetitive sampling of inputs caused the simulation to organize encodings of learned cues into a hierarchical memory that uncovered statistical relationships in the cue environment, corresponding to the performance of hierarchical clustering by the biological network. Simplification led to characterization of those parts of the network responsible for the mechanism, resulting in a novel, efficient algorithm for hierarchical clustering. The hypothesis is put forward that these corticobulbar networks and circuitry of similar design in other brain regions contain computational elements sufficient to construct perceptual hierarchies for use in recognizing environmental cues. PMID- 2315703 TI - 1990 guide to biotechnology products and instruments. PMID- 2315704 TI - Cartilage degradation: is there a place for chondroprotective agents? A symposium of the American College of Rheumatology. Cincinnati, Ohio, June 17, 1989. Proceedings. PMID- 2315706 TI - Clinical aspects of chrondroprotection. PMID- 2315705 TI - Cartilage degradative enzymes in human osteoarthritis: effect of a nonsteroidal antiinflammatory drug administered orally. AB - The activity of stromelysin and collagenase was determined in fibrillated human OA cartilage using labeled proteoglycans and type II collagen as substrates. In vitro paracetamol had no effect on metalloprotease whereas TA induced a significant inhibition of stromelysin. In cartilage and synovium from nine patients treated with TA and nine patients treated with paracetamol during 8 weeks before surgery for hip OA, stromelysin activity was significantly lower in the TA than in the paracetamol group. The results suggest that TA has a potential chondroprotective effect in OA. PMID- 2315707 TI - [Macroscopic and microscopic appearance of arterial stumps in limb segment amputation]. AB - Until now, it has been assumed that in arterial lesions invagination of the intimal layer occurs. In a thigh and an upper-arm amputation this assumption was scrutinized. No hemorrhage or hypovolemic shock occurred in either case despite total amputation. The brachial and femoral arteries were closed and pulsed visibly within the soft tissue. Histology showed no invagination: the adventitial layer was drawn over the open lumen, which was filled with an extensive thrombus. Therefore, in these cases occlusion of the artery is presumed to occur by means of a fingertrap mechanism of the adventitia and the interaction of collagenous fibers with platelets. This hypothesis will be tested in an animal experiment. PMID- 2315708 TI - [Experimental over-stretching of the femoral artery in the sheep in situ]. AB - Arterial lesions associated with fractures or luxations are thought to be caused by an overstretching mechanism. In this paper we would like to elucidate this mechanism in an animal model. Eight sheep (mean age 1.7 years, mean weight 67 kg) were placed under general anesthesia and their femoral arteries prepared. Before stretching, a lesion was induced by crushing the artery with a blunt household wire clipper, so that the adventitial layer was not damaged. With a balloon catheter (inserted through a vessel branch) rupture of the intimal and medial layers was induced. The adventitia was lengthened in situ by tearing with the fingers until a sand-glass form occurred. Two to three minutes later the arteries were occluded proximally and distally so that traction could be stopped. After removal, the vessels were fixated immediately in formaldehyde and embedded in methylacrylate. Using the van Gieson elastica technique, 4- to 6-microns sections were stained. On histological examination of the proximal stump, a thrombus was located in the lumen surrounded by adventitial tissue, which was sheared off from the medial layer for some distance. There was no invagination of the medial layer. The histology of the distal arterial stump is shown in Fig. 6. The findings are similar to those in Fig. 5; in particular, the behavior of the adventitia can be seen here, the thrombus is enveloped by adventitial fibers. These findings can be explained by the three-dimensional network of the adventitia. With regard to the large amount of fibers, a direct platelet-collagen interaction may be responsible for this thrombus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2315709 TI - [Significance of the glenoid labrum for stability of the glenohumeral joint. An experimental study]. AB - In human cadavers we were able to show that the glenohumeral joint is comparable to the model of a physical piston. The labrum glenoidale functions like a valve against atmospheric pressure. It is possible to characterize the behavior of intraarticular negative pressure by the equation (formula; see text). The calculations of the force F of atmospheric pressure tending to resist distraction of the joint surfaces leads to a 95% confidence interval from 6.9 to 22.9 kp. Under a general anesthetic, distraction of the healthy glenohumeral joint also produces negative intraarticular pressure in the area of the fossa glenoidalis in vivo. Joints with a labral tear (Bankart defect) and a chronic instability are not characterized by this phenomenon. A change in intraarticular pressure might stimulate intraarticular pressure receptors. This could be important in functioning as a neuromuscular protection reflex for the joint. PMID- 2315710 TI - [Static stabilizers of the shoulder joint]. AB - Anatomic dissection of 220 cadaver shoulders was performed to find out more about the static stabilizers of the shoulder joint. The static stabilizers, i.e. the glenohumeral ligaments, were always found to be present and strong in healthy shoulders. It was revealed that in anatomic preparations with all the organs removal except the synovial capsule, the capsule ligaments completely stabilized the joint. Anterior dislocation at 45 degrees of abduction was prevented by the superior and medial glenohumeral ligaments, while at 90 degrees of abduction the inferior glenohumeral ligament prevented dislocation. When anterior dislocation has occurred even the coracohumeral ligament must be ruptured. A new finding recorded is that the glenoid labrum is the origin of the inferior glenohumeral ligament and not a triangular static organ enlarging the socket and having a similar function to the menisci in the knee. This ligament is the most important ventral stabilizer of the humeral joint. With the conventional arthrotomy technique the medial and inferior ligaments are immediately cut through and therefore cannot be seen. The inferior glenohumeral ligament must be reconstructed in cases of anterior recurrent dislocation. PMID- 2315711 TI - [Fractured Monteggia pseudarthrosis. An unusual case]. AB - The diagnosis of an ulnar fracture is easily made in Monteggia lesions, but dislocation of the radial head can occasionally be overlooked. In the case presented luxation persisted and ulnar pseudarthrosis developed. In spite of functional disorders, however, the patient still managed to work for 36 years as a lorry driver. An unusual feature of this case is that 40 years after the primary event traumatic fracture of the pseudarthrotic ulna developed and was managed by bone grafting, with good functional results. PMID- 2315712 TI - [Cervical transverse spinal cord injury caused by knife stab injury]. AB - This clinical report refers to a case of quadriplegia caused by a knife stab wound in the cervical spine. Open removal of the knife made it possible to avoid such complications as bleeding and infection. Nevertheless, the tetraplegic signs and symptoms were the result of complete severance of the cervical spinal cord and therefore persisted. PMID- 2315713 TI - Surgical treatment of Achilles tendon ruptures. AB - A total of 75 patients with surgically repaired Achilles tendon ruptures were evaluated with special reference to the status at the end of a standardized short period of cast immobilization (6 weeks). There were 3 (4%) reruptures caused by new adequate trauma, but no other major complications. The final functional result was evaluated with reference to the patients' return to social and recreational activities. Objective measurements reflecting the final functional result are discussed. PMID- 2315714 TI - [The significance of postoperative stability for osseous repair of a multiple fragment fracture. Animal experiment studies]. AB - The significance of postoperative mechanical stability for bony repair of a comminuted fracture was investigated in an animal experimental study comparing four commonly applied operative methods of stabilizing fractures: (1) flate osteosynthesis combined with lag screw fixation after reduction of the fragments; (2) bridging plate osteosynthesis; (3) external fixation; (4) static interlocking intramedullary nailing. As the fracture model, a triple-wedge osteotomy of the right sheep tibia was used. The results of in vitro testing of stiffness (N/mm) of each of the four osteosyntheses was as follows: anatomical plate: 746 N/mm; bridging plate 434 N/mm; external fixation 625 N/mm; nailing 416 N/mm. Eight weeks after the operation, the tibiae were explanted and the contralateral tibiae of six sheep were taken as a control group. The three-point bending test revealed no significant difference in bending deviation: anatomical plate 47.58 +/- 22.57 microns; bridging plate 33.93 +/- 7.67 microns; external fixation 33.83 +/- 8.02 microns; nailing 33.0 +/- 17.23 microns. However, it was noted that there was a slightly higher tendency towards stiffness of the bones after bridging plate osteosynthesis, external fixation and interlocking intramedullary nailing and that the amount of stiffness resembled that in non-operated control animals (25.56 +/- 6.66 microns). On the other hand, anatomical plate osteosynthesis showed less stiffness. To assess the tensile strength at the osteotomy area, bone samples were prepared and tested for failure on a material testing machine. The tensile strength of the bone samples showed a distinct difference in all experimental groups according to their anatomical location.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2315715 TI - [Blunt injuries of the gastrointestinal tract]. AB - This study represents our experience with severe blunt gastrointestinal injury in 29 polytrauma and 3 solitary trauma patients. The primary diagnosis was missed in intestinal perforation (4x) and mesenteric disrupture (1x). In 2 other patients contusion of the gastrointestinal wall led to postprimary perforation. The average mortality was 21.8%; only 2 patients died from abdominal sepsis. Blunt gastrointestinal trauma differs from penetrating injury as far as the diagnostic and therapeutic aspects are concerned. In some cases, explorative laparotomy alone leads to early diagnosis. For sufficient management, the blunt contusion/compression aspects must be taken into account. PMID- 2315716 TI - [Rare, bilateral posterior shoulder dislocation. A case report]. AB - Posterior shoulder dislocation is a very rare injury, accounting for only 1-2% of all shoulder dislocations. It is very often misdiagnosed because its clinical symptoms are not characteristic and the X-ray pictures are often misinterpreted. In many cases this means delayed treatment and impaired shoulder function. The most common cause of posterior shoulder dislocation is an epileptic seizure. In approximately 50% of all cases a ventral impression fracture of the humeral head is diagnosed. This is known as the "reverse Hill-Sachs lesion". About 10% of all posterior shoulder dislocations are associated with fracture of the lesser tuberosity of the humerus. In this paper a case of bilateral posterior shoulder dislocation with bilateral fracture of the lesser tuberosity of the humerus is described. The luxations were caused by an epileptic seizure following chronic alcohol abuse. Following early commencement of an exercise programme excellent results were obtained, and no redislocations occurred. PMID- 2315717 TI - [The coxal end of the femur. An architecture following strict rules]. AB - In order to combine the dynamic hip screw with a plate that anchors the greater trochanter, detailed measurements of the greater trochanter are necessary and its relation to the femoral head and neck must be studied. The hips in 200 X-ray films in the AP view were measured. The radiographs were obtained from 46 males and 87 females (69.2 +/- 16.9 years old) without hip disease. Concerning the neck shaft angle, no selection was done. The axis of the femoral head and neck was drawn; a second horizontal line passed through the apex of the lesser trochanter. Both lines intersected the lateral cortex of the femur. The distance between those two intersections was measured: d = 0.41 +/- 0.28 cm. In the next step, 74 human femora were obtained from 21 females and 17 males (79.9 +/- 9.0 years old). A special gauge was fixed at the lateral site of the femur. Using this gauge, the size and shape of the greater trochanter were measured: (1) the apex of the greater trochanter lay exactly on the line, which was determined by the lateral cortex of the femoral shaft (+/- 0.4 cm); (2) the maximum lateral extension of the greater trochanter was measured half-way from the lesser trochanter niveau to the apex of the greater trochanter (minor-major distance: 6.09 +/- 0.82 cm; minor lateral maximum distance: 3.03 +/- 0.59 cm); (3) the maximum lateral extension of the greater trochanter measured 11.4 +/- 3 mm. PMID- 2315719 TI - [Synovectomy in knee infection. Late results]. AB - When short-term conventional treatment of pyogenic knee-joint infections does not relieve the symptoms, in most cases the patients can be cured with an synovectomy within a few weeks. In this procedure, the infected site, the synovial membrane, is excised. Immediately after the operation, functional treatment starts to improve joint mobility and cartilage nutrition. Of 17 synovectomies followed up after an average of 9.5 years, 10 were free of pain, 13 patients were able to walk without restriction, 12 could flex their knee more than 120 degrees, and 9 knees showed no radiographic signs of osteoarthritis. This 10-year follow-up shows that early synovectomy and functional treatment can lead to good long-term results. Therefore, this procedure can be recommended. PMID- 2315718 TI - [Mobilization in anesthesia and arthrolysis in postoperative knee joint stiffness]. AB - Knee joint stiffness first of all calls for physiotherapy, ranging from exercise therapy to a passive-immobilization splint. If no progress can be achieved, narcosis mobilization and brisement modere should be done. If narcosis mobilization does not yield acceptable results, then surgical dissolution and arthrolysis should be performed. Thirty-seven patients with painless fibrous knee joint stiffness following ligament reconstructions showed a reduction in mobility of 0 degree-20 degrees-80 degrees on average. After narcosis mobilization, full extension and bending could be achieved in 28 patients. In 9 patients, arthrolysis had to be carried out. At follow-up examination 1/2 to 3 1/2 years later, all 37 patients showed an increase in movement of 0 degree-0 degree-125 degrees on average. The "relative gain," the quotient of achieved and possible gain of movement in percentage, ranged from 88% to 96% on average. Other kind of loss of movement, patient age, or sex had no influence on the results. Twenty-six patients were able to participate in sports again due to the increase in movement potential. In the last few years, we have come to prefer arthroscopical arthrolysis instead of surgical arthrolysis when narcosis mobilization fails. PMID- 2315720 TI - [Force couple splint in unstable dislocation fracture of the interphalangeal joint]. AB - A well-documented percutaneous method in the treatment of fracture dislocations of the PIP joint, the force couple splint technique according to Agee produces good functional results in these rare injuries. This paper presents our own modification with mass-produced preconstructed couple splints, which can be combined precisely with the elements of a mini-external fixation system. PMID- 2315721 TI - [Follow-up of extensive burns in an HIV positive patient. Case report]. AB - The case of a 33-year-old HIV-positive patient who suffered from second- and third-degree burn injuries involving 30% of the body surface is reported. She was treated by early tangential excision of the burnt skin and split-thickness mesh grafting. The burn wounds healed without complications within the usual time, with excellent cosmetic and functional results. In spite of the successful treatment, she suffered from fever and various infections for several months. With the appearance of these constitutional symptoms, we recognized the AIDS related complex. Her general condition deteriorated continuously and 10 months after the accident she had to be admitted to a hospital again. The skin had nevertheless healed perfectly and in spite of not having compression treatment for the grafts or physiotherapy, she did not show any signs of hypertrophic scars. Some important conclusions drawn from this case are discussed. The fact that healing occurred without complications is in contrast to the results reported in the literature concerning impaired wound healing in AIDS patients with anorectal surgery. We therefore believe that the reluctant and perhaps even anxious attitude of the medical and nursing staff towards performing technical and expensive procedures in HIV-positive burn patients is not justified. PMID- 2315722 TI - Pathophysiologic interactions: pregnancy and associated illnesses, Part I. PMID- 2315723 TI - Clinical ethics: a role theoretic look. AB - The new phenomenon of clinical ethics is analyzed from a role theoretic perspective that differentiates consulting, teaching, watching, and witnessing. Teaching and consulting are seen as main role alternatives in clinical ethics practice, with watching and witnessing defining transitional states that reveal the complexity of clinical ethics. The problem of the legitimation of clinical ethics is discussed in terms of legal, professional, and social accountability and authorization. It is argued that the problem of legitimation is tied up with the related issue of expertise that, in turn, reflects the complex role alternatives of consulting, teaching, watching, and witnessing. Finally, the question of methodology and practice of clinical ethics is explored in connection with the four role alternatives delineated. PMID- 2315724 TI - Women and AIDS. AB - This article describes the epidemiology of acquired immunodeficiency syndrome (AIDS) in women in the United States. Comparisons of female and male transmission categories are made and emphasis is placed on the heterosexual transmission and undetermined risk categories for women. Since its onset in 1981, AIDS has affected males predominantly and female AIDS cases have not received as much attention. AIDS education efforts have not targeted women as much as men, despite women's vulnerability to infection, especially through heterosexual transmission. AIDS tends to generate many issues that concern women's sexuality--contraception, pregnancy and abortion among them. Some of the special problems that women with AIDS face are discussed. Women's role as caregiver for persons with AIDS also is examined. Attention is directed to the ways in which AIDS is associated with the traditional female role. PMID- 2315725 TI - Behavioural factors affecting physical health of the New Zealand Maori. AB - A major factor in the aetiology of illness is the behaviour of individuals with regard to certain risks and hazards of the environment. The Maori of New Zealand have been shown to be at greater risk of illness and death than their non-Maori counterparts. It is estimated that a significant proportion of this excess morbidity and mortality can be attributed to at least four behavioural factors: smoking, obesity, alcohol use and accidents. This paper examines the inter cultural differences in these factors, both from a contemporary and an historical perspective. Some of the reasons for the continuation of these adverse patterns of behaviour are explored, in particular the role of psycho-cultural stress. Some possible mechanisms of effecting behavioural change in modern Maori society are discussed. PMID- 2315726 TI - The biocultural context of social networks and depression among the elderly. AB - The association between the size and structure of social networks and the prevalence of depressive symptoms was examined in a population-based study of 1615 men and women age 65 years and older. Age was significantly associated with marital status, social network index quartile, and the social relationship to the primary source of support. Women and men differed with respect to current marital status, number of close friends and relatives, frequency of face-to-face contact, and participation in voluntary associations and religious institutions. Regardless of their marital status, women were also less likely than men to point to a spouse as their primary source of support. Beck Depression Inventory mean scores and rates of depressive symptoms were inversely associated with social network index and participation in voluntary associations and religious institutions for both men and women. Individuals with no primary source of support or who depended on a relative had significantly higher than expected mean scores and rates of depressive symptoms. Both social network index and social distance to primary source of support were independently associated with depression after controlling for age, sex, and number of chronic conditions. Participation in voluntary associations, social distance from primary source of support, church membership, and number of close friends were also significant independent predictors of depressive symptoms. Results indicate that depressive symptoms are inversely associated with the size of social networks. The structure of these networks, in turn, is influenced by biological factors such as age, physical disability, and mortality of network members, and by culturally determined rules that define the individuals and institutions available for support. However, these rules appear to differ for men and women. PMID- 2315727 TI - The mundane ailment and the physical self: analysis of the social psychology of health and illness. AB - Using interview data from adult men and women who participated in an ongoing study of self-care, the research focused on the experience of mundane ailments as a promising topic for research in the social psychology of health and illness. Phenomenological analysis of respondents' accounts of everyday ailments generated concepts of 'the physical self', which expands interactive or dramaturgical concepts, and 'the health biography'. These concepts, when linked to analysis of interaction lead to a more dynamic sociology of health, illness, care and cure. PMID- 2315728 TI - The confounding of occupation and smoking and its consequences. AB - A strong pattern in smoking behavior can be demonstrated, in which smoking is much more prevalent among those occupational groups (and social strata) that are also more exposed to hazards in the workplace and much less prevalent among those groups less exposed to such hazards. As a consequence, comparing individuals with greater to those with lesser exposure to tobacco also compares groups that differ with respect to occupational exposure to dust, fumes and toxic substances and with respect to occupationally related lifestyle factors. Analyses of the U.S. National Health Interview Survey show that smoking and occupation are substantially confounded among individuals differing by (1) amount of smoking; (2) smoking cessation; (3) types of cigarettes smoked; (4) age of starting to smoke; and (5) exposure to more or less environmental tobacco smoke at home. This confounding between types of work and proximity to tobacco smoke may have masked relationships between type of employment and disease. But it is difficult to disentangle the effects of occupation and of smoking from each other without well planned further studies because (1) of the difficulty of estimating occupational effects and simultaneously adjusting for healthy worker effects, (2) satisfactory techniques for estimating relative effects of intertwined variables make demands on the quality and quantity of data that are not met by presently available data, and (3) there may be deeply rooted social and psychological attitudes toward effects of work versus effects of lifestyles that tend to bias investigative work. PMID- 2315729 TI - Gender differences in the effect of unemployment on psychological distress. AB - In this paper we examine whether unemployment has a differential impact on the expression of psychological distress among men and women. Based on the traditional centrality of the work role to men and the family role to women, we defined several key domains that might affect unemployed men and women differentially: family circumstances, concerns and worries about children and family; coping responses; social support and social integration; and the centrality of the work role. While the study population either were or hoped to be in the labor force and had dependent children, they varied in their marital status and whether they were the custodial parent. Using data collected in Baltimore from those who had been unemployed but had returned to work, those who had remained continuously unemployed for a year, and those who had been continuously employed, we compared the patterns of men's and women's reactions to unemployment. The important differences in psychological symptoms in this population were related to employment status, problems with parenting, financial difficulties, perceived lack of social support, hostility, and feelings about unemployment. By and large, the patterns of these relationships were similar for men and women. These findings suggest that when gender differences in psychological distress are found they may be due to differences in role configurations of men and women rather than intrinsic gender differences. PMID- 2315730 TI - Injury mortality in American Indian, Hispanic, and non-Hispanic white children in New Mexico, 1958-1982. AB - Childhood fatalities from injuries are a serious public health problem in New Mexico, a state which ranks second in the nation in injury-related mortality rates. To determine the extent of injury mortality in children in this state, and to examine time trends and differences in mortality rates in New Mexico's American Indian, Hispanic, and non-Hispanic white children aged 0-14 years, we analyzed vital records collected from 1958 to 1982. American Indian children experienced the highest mortality rates from all external causes combined. Among all three major ethnic groups, children aged 0-4 years were at the highest risk for injury fatalities. Unintentional injuries accounted for 85% of all injury related deaths. Motor vehicle crashes and drowning were the first and second leading causes of death in all three groups, while other important causes of death included fire, choking on food or other objects, poisoning, and homicide. Although the fatality rates on most types of injuries decreased over the 25-year period, childhood fatality rates for motor vehicle crashes and homicide increased in each ethnic group. Despite the overall decrease in injury mortality rates in New Mexican children, the rates are excessively high compared to other states, especially in American Indian children. PMID- 2315731 TI - Barriers and motivators to prenatal care among low-income women. AB - Substantial evidence exists which links prenatal care to improved birth outcomes. However, low-income and nonwhite women in the United States, who are at greatest risk for poor birth outcomes, continue to receive the poorest prenatal care. The purpose of this study was to identify and compare barriers and motivators to prenatal care among women who lived in low-income census tracts. The stratified sample included recently delivered white, black and American Indian women who received adequate, intermediate, and inadequate prenatal care. Interviews were conducted which focused primarily on the women's perceptions of problems in obtaining prenatal care and getting to appointments. Results indicated that women with inadequate care identified a greater number of barriers and perceived them as more severe. Psychosocial, structural, and socio-demographic factors were the major barriers, while the mother's beliefs and support from others were important motivators. The predictive power of selected barrier variables was examined by a regression analysis. These variables accounted for 50% of the variance in prenatal care use. The results affirm the complexity of prenatal care participation behavior among low-income women and the dominant influence of psychosocial factors. Comprehensive, coordinated and multidisciplinary outreach and services which address psychosocial and structural barriers are needed to improve prenatal care for low-income women. PMID- 2315732 TI - Low birth-weight and pre-term delivery in South-east Asia. The WHO International Collaborative Study of Hypertensive Disorders of Pregnancy. AB - Population-based data from 10 centres in Burma, Thailand, China and Vietnam, have been analysed to assess those social and environmental factors which may be associated with pre-term delivery and low birth-weight. The philosophy behind the study was that if the same association was found in different countries, then the association may be causal; if associations differed in the various countries, then causality was unlikely. The major findings were as follows: a strong association between low birth-weight and pre-term delivery and the unmarried state (RR 1.64, 1.39), a consistent reduced risk of pre-term delivery when the father was in a managerial post (RR 0.77), an excess risk of pre-term delivery if the mother was a housewife (RR 1.16), lifting heavy objects at the time of quickening (RR 1.63) or frequently bending and stooping at the time of quickening (1.15). Strong associations were found with both paternal and maternal education levels but these were strongest for the mother's education level. The association was far stronger for pre-term delivery than for low birth-weight and it is assumed that the low birth-weight effect is secondary to pre-term delivery. The only variation with maternal age concerned an excess of low birth-weight among teenage mothers, but not of pre-term delivery, and an excess of low birth-weight but not pre-term delivery among mothers with small head circumferences or small arm circumferences. We conclude that the aetiology of growth retardation and pre term delivery are probably different in South-east Asia, and point out the need to elucidate further the strong variation with education level. PMID- 2315734 TI - Long-term patterns of general practice consulting behaviour: a qualitative 9-year analysis of general practice histories of a working-aged rural Finnish population. AB - The 9-year practice histories of 100 working-aged residents of the rural municipality of Kaavi in Finland were analysed. Based upon an analysis of these histories, an interview of the 81% who participated and the personal patient knowledge of the author from his work as a general practitioner for 7 years in the community, 78% of the persons studied could be classified into six categories in a qualitative typology of consulting patterns. The descriptive names of the categories, together with their proportionate sizes and the mean annual consultation rates within the categories were: (1) 'Healthy and competent' (16%; 1.03); (2) 'Contented returners' (12%; 3.28); (3) 'Information seekers' (8%; 4.08); (4) 'Support seekers' (15%; 4.62); (5) 'Drifters' (21%; 2.21) and (6) 'Those hard to convince' (6%; 3.59). The rest (22%; 1.15) could not be classified. The implications of the typology are discussed from two standpoints: (1) In view of the current Finnish debate on the need for fee deterrents for the use of public general practitioner's services. (2) The potentials and limitations of different broad strategies suggested for general practice. PMID- 2315733 TI - Social support, stress and functional status in patients with osteoarthritis. AB - We investigated the relationship among social support, stress and functional status in 439 patients with osteoarthritis (OA). OA is among the most prevalent diseases affecting American adults and is a major contributor to functional impairment, morbidity, and utilization of health care resources. This study examines whether the impact of social support upon health was direct or indirect (i.e. it was present only when respondents were exposed to stressors). We also wanted to explore the relationship between functional status and specific dimensions of support (i.e. self-esteem, appraisal, belonging, and tangible support). Functional status (psychological disability, physical disability, pain) was assessed with the Arthritis Impact Measurement Scales (AIMS). Multiple regression suggested that exposure to stressors and low self-esteem support were associated with increased disability along all AIMS dimensions; appraisal support was not correlated with any AIMS score. Also, physical disability was associated with being older and having less tangible support (R2 = 0.17); psychological disability with being younger, caucasian, and having less belonging support (R2 = 0.47); and pain with being younger, caucasian and having less education (R2 = 0.15). In no instance was there empirical support for the buffering model. Self esteem appeared to be the most, and appraisal the least, consistent social support dimension when predicting functional status. While exposure to stressors negatively affected all AIMS dimensions, its impact was greatest with respect to psychological disability. We conclude that social support had a direct, rather than indirect, impact on functional status. Future research should consider separately the impact of distinct social support dimensions. PMID- 2315735 TI - Baby Doe regulations and medical judgment. AB - The potential for conflict between social policy and medical judgment can be examined in relation to the 'Baby Doe' regulations issued by the U.S. Federal Government in 1984. These regulations identify the circumstances in which medical treatment may be withheld from handicapped infants. This article reports on a national survey of perinatal social workers which compared their responses to the answers of physicians to similar questions published earlier. These social workers failed to express a conflict between sound medical judgment and the federal regulations when confronted with three hypothetical cases. The same was true in the published study of physicians but that data was erroneously interpreted as providing evidence of a conflict between medical judgment and federal regulations. On some general opinion statements, the social workers were similar to physicians in their criticism of these regulations but on others they were equivocal. While the majority of responses of social workers to other questions about these regulations was rather similar to the responses of physicians, the social workers were found to be more inclined than physicians to express the view that these regulations were needed to protect the rights of handicapped infants and the view that the physician's practice had been changed as a result of these regulations. PMID- 2315736 TI - Social class and health in youth: findings from the west of Scotland twenty-07 study. AB - The assumption that social class inequalities in health are a persistent feature of the life-course has been questioned in a recent issue of this journal. On the evidence of mortality and chronic illness, the pattern in youth in Britain appears to be characterised by the lack of class differentials, a striking contrast to early adulthood where the familiar picture of health inequalities is observed. The possibility that this finding of relative equality in youth is a consequence of the limited, and potentially inappropriate, health indicators used has now been tested on a cohort of 15-year-olds in the West of Scotland. On a range of indicators, from subjective assessments to objective physical measures, very little evidence of class variation in health is found. The possible transience of the youth pattern is, however, indicated by findings from a cohort of 35-year-olds in the same study, among whom marked class gradients in health are apparent. Possible explanations for the transformation of a pattern of relative class equality in youth into one of inequalities in adulthood are discussed. PMID- 2315737 TI - Cow dung, rock salt, and medical innovation in the Hindu Kush of Pakistan: the cultural transformation of neonatal tetanus and iodine deficiency. AB - In mountain villages of Chitral District in northwestern Pakistan, dried cow dung is used as Westerners would use talcum powder when babies are swaddled and rock salt is consumed in tea and other foods. Both substances are esteemed as conveying beneficial 'heat' and 'strength'. Unfortunately, however, cow dung sometimes contains a bacterium that causes neonatal tetanus, and the resulting toxin may enter through the baby's unhealed umbilical cord and cause death. Further, rock salt contains no iodine, and Chitral's soil is so iodine-deficient that goiter is very common. Thus local health workers advocate use of talcum powder rather than cow dung, immunization against tetanus, and replacement of rock salt by powdered iodized salt. The present report documents widespread community acceptance of these innovations despite the fact that the biomedical model of tetanus and goiter was not well understood and indigenous concepts of the causes of the diseases remained virtually undisturbed. Most of the villagers were Ismaili Muslim followers of the Aga Khan; their receptivity to such health messages was influenced by the high value that their religion places on advancement through 'education' and was correlated with their proximity to Ismaili health workers whom they trusted. A major implication of this research for primary health care programs is that when one is attempting to change existing health practices, explication of biomedical models should not be the only focus of concern. Attentiveness to the context in which behavior changes are introduced and interpreted is at least equally important. Further, the fact that new knowledge was added to the old without replacing it illustrates the complexity of human cognition and points to limitations in the KAP (knowledge attitude-practice) model of health belief and behavior. This report adds to a small but important body of literature documenting the dynamic nature of medical pluralism in the developing world. PMID- 2315738 TI - A pilot study of attendance for breast cancer screening. AB - Previous research has identified some characteristics related to attendance for breast cancer screening, but few research findings carry practical implications for the optimum organisation of the service. The present study describes the reactions of women attending one of the first breast screening units to be established in the U.K. following government directives. Responses to the invitation to be screened and reasons for attendance suggest ways in which the idea of screening can be conveyed in health education. Practical problems were few, but some negative features of the design of the screening unit and of the experience of being screened were identified. Recommendations for the organisation of breast cancer screening are presented using the typology of factors influencing health behaviour developed by Green et al. PMID- 2315739 TI - Neighbourhoods for health service administration. AB - Health and social service administrators are increasingly realising the importance of adopting a community or neighbourhood scale for the organisation and delivery of many different services. The concept of neighbourhood is an elusive one, yet it has been used for a number of planning purposes. This paper reviews the nature and utility of neighbourhoods and demonstrates the variety of territorial units used by different statutory agencies. The results of an empirical exercise in North Staffordshire are reported as an example of the practical issues involved. Neighbourhoods are identified with a view to being used for data collection, the delivery of health care services and the possible implementation of health forums. PMID- 2315740 TI - Homosexual and bisexual men's coping with the AIDS epidemic: qualitative interviews with 10 non-HIV-tested homosexual and bisexual men. AB - This paper describes how the threat of HIV infection is appraised and coped with by homosexual and bisexual men. Very little is known about men who do not want to be HIV tested, thus non-HIV-tested homosexual and bisexual men have been interviewed in depth about themes concerning their lives during the AIDS epidemic. Men with sexual risk behaviour appeared to be very reluctant to participate, and therefore six men with safe sexual behaviour and four men with unsafe sexual behaviour were interviewed. The results showed that all the men were well informed about AIDS and preventive measures. Reasons for not wanting a test were fear of psychological distress caused by a possible positive test and the fact that no treatment is available. The men who had adopted safe sex appraised their sex lives to have suffered a minor loss but found that sexuality played a subordinate role compared to trust and friendship. The men with risk behaviour considered sexuality to play an important role in their lives. They found condoms a barrier to intimacy and used defensive strategies to manage stress. Most of them were able to exchange social support with their network but had difficulties in setting their own limits. All four men had experienced undertreated traumatic events in their past. The results indicate that knowledge of AIDS and satisfactory social support do not necessarily result in safe sexual behaviour. The role of undertreated traumatic events forming barriers against adopting safe sexual practices should be further studied. Proposals are put forward for future health education programmes. PMID- 2315741 TI - Health belief and compliance with screening for fecal occult blood. AB - Additional data regarding compliance with screening for occult bowel neoplasm using hemoccult II is reported in this paper. The effects of 'health beliefs' and 'barriers to compliance' among a subset of 256 compliers and 166 noncompliers drawn from the population of 5003 patients previously screened were analyzed. Health belief variables as predictors of compliance were found to be age related. Being 'too busy' was frequently given as the reason for noncompliance in all age groups. The percentage of patients correctly classifies as to compliance was appreciably higher than in the earlier study which considered demographic data and the effect of diet restriction. These findings carry implications extending into clinical practice. PMID- 2315742 TI - Perceptions of risk, dilemmas of policy: nuclear fallout in Swedish Lapland. AB - This paper concerns risk perceptions of Swedish Saami reindeer herders in conjunction with the Chernobyl nuclear disaster. Focus is also placed upon their experiences of damage and their efforts to deal with these problems. Data relating to these social aspects of the Chernobyl event come from interviews with members of Saami herding families. The initial governmental policy of establishing a simple contamination limit for the marketability of all foodstuffs was beset with shortcomings. I propose that all contaminated foods should be labeled with contamination specifications along a fully graded scale. In addition, there should be consumer education and recommendations for the entire population, not just one segment. An absolutely necessary step in the construction of valid policies is the health calibration of low-dose radiation. Without such knowledge, any marketability limit is suspect. With such knowledge, policy can be firmly based on human health. PMID- 2315743 TI - Secular trends and the pattern of growth in arctic populations. AB - Examinations of growth patterns in Arctic populations suggest that Inuit/Inupiat (Eskimo) children display a unique pattern relative to European or continental U.S. children. This pattern--high weight for height--becomes established early in life and it has existed for as long as researchers have Inuit or Inupiat data. This paper will examine the growth pattern relative to the NCHS reference standard, using recent data from the Arctic and several indices combining height and weight. Of particular concern will be the persistence of this pattern in the face of secular trends in growth that have occurred over the past 50 years. Trends for height increase have been greater than those for weight but weight for height still remains well above the 50th percentile of the U.S. reference for these Arctic groups. PMID- 2315744 TI - Medicalization, public policy and the elderly: social services in jeopardy? AB - This paper examines the medicalization of community-based services for the elderly; a process of restructuring to provide more highly medical services to a frail older population at the expense of providing a broader range of social and supportive services to older persons with varying levels of need. Medicalization is tied to changes in government policy (particularly Medicare reimbursement) which have led to increased competition within the health and social service sector. The paper utilizes data on services, policy impact and staffing from the DRG Impact Study conducted at the Institute for Health and Aging (UCSF), a 3-year study of the impacts of federal policy on 7 types of community providers of services to the elderly. Data are presented from telephone interviews conducted at two points in time (1986 and 1987) with directors of a representative sample of home health agencies (HHAs). Findings include: HHAs were more likely to report adding highly medical services and cited social/supportive services (as opposed to highly medical and/or highly technical services) as the most commonly requested services they cannot provide. Policy effects and societal implications of the medicalization of home care are considered. PMID- 2315745 TI - Nutritional status and the incidence and duration of diarrhoeal disease among children in northeast Thailand. AB - In Thailand, diarrhoeal diseases are among major community health problems. The relationship between nutrition status and the incidence and duration of diarrhoea was studied in a sample of 1,117 mothers and 1,364 children under the age of 5 years. The findings are reported and analysed. PMID- 2315747 TI - Referrals to physiotherapy: the relation between the number of referrals, the indication for referral and the inclination to refer. AB - This article studies the relation between the referral rate and the type of patients general practitioners refer for physiotherapy. The study population consists of GPs participating in the Netherlands' Sentinel Stations Network, who recorded data on all referrals to physiotherapy during one year and filled in a questionnaire. Results show that the pattern of referral indications of high referring GPs does not differ systematically from that of low referring GPs. High referring GPs evaluate their patients complaints more as purely or mainly somatic. High referring GPs were no more inclined to give in to their patients demands, had busier practices, closer relations with physiotherapists and viewed their knowledge of physiotherapy as more satisfactory than low referring GPs. Some policy implications are discussed in respect to these results. PMID- 2315746 TI - Gender differences in medical student distress: contributions of prior socialization and current role-related stress. AB - Gender differences in psychological distress among future physicians are addressed from contrasting role-related stress and socialization-based vulnerability perspectives. A medical student cohort was surveyed at medical school entrance and after one year of training, focusing on earlier familial relationships, personality and social support resources, perceived medical school stressors and alcohol consumption and depressive and anxiety symptomatology. Relative to socialization perspectives, the sexes manifested more similarities than differences at time 1, although the females manifested lower overall psychopathology, but greater perceived paternal overprotection in childhood. Relative to role stress perspectives, both sexes reported increased psychopathology by the time 2 point. The sexes did not differ in perceived medical school-related stressors, while females manifested better social supports at time 2. The psychosocial predictors of increased subjective distress for both sexes included perceived earlier familial relationships and medical school stressors. The only predictor of increased drinking (by males) was time 1 drinking level. Future research on gender roles and distress should assess both male and female modes of psychopathology and should address antecedents of role entrance in addition to the (presumed) consequences of role incumbency. PMID- 2315748 TI - Incongruence between self-reported symptoms and objective evidence of respiratory disease among construction workers. AB - In clinical settings, self-reported symptoms and objective evidence of disease may be poorly correlated. In the present study, symptoms and objective evidence of pulmonary disease were compared in a community sample of construction workers with occupational exposure to asbestos. Symptoms of dyspnea and cough were assessed by a standardized questionnaire. The clinical examination included a chest X-ray, pulmonary function testing (PFT), and a physical examination. Both symptoms and objective clinical findings were strongly related to years in these trades. However, less than 1% of workers reported symptoms in the absence of any clinical evidence of disease. A similar low percentage of workers denied any symptoms yet produced clear evidence of pulmonary disease on clinical examination. Results were interpreted in terms of the variety of factors which have been associated with patients' readiness, and conversely, reluctance to report symptoms. The comparatively low frequency of incongruence between symptoms and objective clinical findings in this study suggests over emphasis of malingering by other authors. Health care might be improved if more attention is given by clinicians and researchers to patients who fail to report symptoms in the presence of disease. PMID- 2315749 TI - The French version of the Nottingham Health Profile. A comparison of items weights with those of the source version. AB - The efficient and reliable assessment of general community health requires the development of comprehensive and parsimonious measures of proven validity. The Nottingham Health Profile (NHP) has been demonstrated to be a reliable indicator of common expressions of discomfort and stress in the general population. The present paper describes its linguistic adaptation into French, the derivation of item weights by Thurstone's method of paired comparisons and the comparison of item weights across various sociodemographic groups. There is more similarity than variation on the valuation of the state of health explored by the NHP between the French and the British population as little inter-cultural or inter linguistic variations were found. The differences in judgement of severity elicited across sociodemographic groups in the French sample cast some doubts on the relevance of general weights for use in population surveys. PMID- 2315750 TI - Waiting for the family legacy: the experience of being at risk for Machado-Joseph disease. AB - Every offspring of an individual with Machado-Joseph disease has a 50% chance of inheriting the disease-causing gene, and symptoms usually do not appear until adult life, usually between the ages of 20 and 40. There are no predictive screening tests available for the disease. This paper, drawn from data collected as part of a larger study of the malady among descendants of Azorean-Portuguese in the Azores Islands and in northern California, explores the subjective state of genetic risk. Although individuals at risk vary in their reactions to the threat of Machado-Joseph disease, there are commonalities of concern that cross cut individual differences. These differences and commonalities are important for what they might tell us about the experience of genetic risk in general, as well as Machado-Joseph disease in particular. PMID- 2315751 TI - Double bind and disability: the case of traumatic head injury. AB - This paper presents ethnographic data to support the double bind model of communication most recently described by Alexander. Using traumatic head injury as an example, an interactive view of paradoxical communication was taken focusing on the disabled, the family, and service providers. A brief discussion of head injury in the U.S. is followed by a delineation of the principles of the model. A number of specific binds are described based on perceptions of caregiving, private and public performance of the head injured, the invisibility of the disability, and economic disincentives to employment of the disabled. The paper expands the model based on the disability experience including illustrations of split binds, contextual communication and biological aspects of double bind. PMID- 2315753 TI - Ambiguity and difference: families with dwarf children. AB - The social complexities of dwarfism differ from those of other conditions included under the rubric of physical disability because of the historical mystique of dwarfism and the fact that most dwarfs do not have severe physical restrictions on their activities. The ambiguities around being a dwarf in American society foster ambivalence and multiple perceptions and understandings of daily life experiences for parents and their dwarf children. This paper will examine areas in the child's career in which these ambiguities are played out. The data were gathered through interviews with 25 families, and through attendance at meetings of Parents' Groups of Little People of America from 1976 to 1987. PMID- 2315752 TI - Rehabilitation ideology and respiratory support technology. AB - This paper examines the impact changing ventilation technology and the ideologies of rehabilitation medicine on the long term adaptations of people with post-polio respiratory disability. Multiple in-depth interviews with 10 respirator-dependent people indicates that cultural ideologies learned during rehabilitation continue to effect the adoption of technology and daily management of respiratory insufficiency. Adaptive strategies through which benefits of technology are maximized and the social costs minimized, have transformed rehabilitation ideologies and moderated the late, aging-related effects of poliomyelitis. PMID- 2315754 TI - The concept of self in the context of crisis: a study of families of the severely brain-injured. AB - Patients in coma and a persistent vegetative state (PVS) lack cognitive ability, but may survive for prolonged periods. They present their family members with complex and difficult questions with respect to their treatment and care ranging from the type of technical support they should receive to the nature of adjustments in daily life to accommodate new circumstances and needs. Such decisions are often made in the face of considerable socio-economic and moral constraints with little if any medical guidance and no firm cultural guidelines. Based on a continuing study of families of patients in coma and PVS living in the greater New York area and using the case-study method, this paper argues that such patients and their families find themselves in socially ambiguous and isolated positions which can best be described through the anthropological concept of liminality. Further, it is hypothesized that decisions concerning these patients will in part reflect the way in which family members define the concept of self. PMID- 2315755 TI - Stigma, biomedical efficacy, and institutional control. AB - This paper explores the role of biomedical efficacy in the rehabilitation of the disabled. Ethnographic data are presented from two studies, one concerned with the prevocationally blind, the other with the institutionalized chronically mentally ill. A comparison of rehabilitation for these two groups suggests that when disabilities do not respond well to biomedical interventions, inconsistent and contradictory interpretations and policies about etiology, therapy, and post treatment prognosis are likely to flourish. These conflicts may, in turn, increase pressure on rehabilitation institutions to maintain control over their clients. This paper addresses these issues in order to stimulate discussion about the relationship of different kinds of disability to stigma and rehabilitation. PMID- 2315756 TI - Facing AIDS: reactions among police officers, nurses and the general public in Sweden. AB - This study compares police officers and registered nurses and the general public concerning their perceptions of the risk of HIV infection, attitudes toward HIV infected individuals, and attitudes toward measures used to fight the AIDS epidemic. Information was obtained through mail questionnaires sent to random samples of individuals, aged 25-44 years, from the 3 groups. The samples included 525, 501 and 1600 individuals respectively. Response rates were 85, 93 and 74%. The study showed good knowledge concerning verified carriers of HIV infection (blood, sperm, vaginal secretion, etc.). A widespread fear of unverified carriers of infection (public toilets, kissing on the mouth) existed particularly among the public and police officers. Negative attitudes toward HIV-infected individuals and demands for compulsory measures were common among all groups, although least common among nurses and most common among the police. Positive relationships were established between the fear of unverified carriers of infection, repulsive attitudes toward individuals infected by HIV, and demands for compulsory measures. PMID- 2315757 TI - Households, resources, and child health in a self-help settlement in Cairo, Egypt. AB - The health of children is produced within the social structures of daily life. This paper looks at children in a large, self-help settlement within the city of Cairo, Egypt. It shows how the social and physical conditions of the community, and the specific resources of households, condition the processes by which better or worse health is produced for children under the age of 3. Health status is measured by anthropometric observation and by household survey. Variables are defined and positioned in the analysis according to a framework that links biological outcomes to social determinants through intermediate factors. The analysis makes use of multivariate modeling, as well as qualitative data collected by direct observation in the community. PMID- 2315758 TI - A comment on the meaning of numerical valuations of health states. PMID- 2315759 TI - Social workers' comfort in providing services to AIDS patients. AB - With the steadily increasing number of people infected with the human immunodeficiency virus, social workers are being called on to play a key role in meeting the complex psychosocial needs of infected individuals and their significant others. To understand more about social workers' levels of comfort in providing services to individuals with acquired immune deficiency syndrome (AIDS) and their family and friends, a survey of social workers in 12 hospital centers was carried out. The majority of social workers were found to be compassionate and sensitive to the needs of this patient population. Several factors were found to be associated with comfort, including various background characteristics, knowledge about the disease, homophobia, negative moral attitudes toward people with AIDS, and the reactions of family and friends. In this article, the authors review these findings and discuss their implications for social work education and practice. PMID- 2315760 TI - Cuba's health care policy: prevention and active community participation. AB - In Cuba, health care is considered a human right for all citizens; health care is therefore a national priority. Cuba's health policy emphasizes prevention, primary care, services in the community, and the active participation of citizens. These emphases have produced an impressively high ranking on major health indicators, despite economic handicaps. The Cuban experience demonstrates the influence of ideological commitment and policy-making on the provision of health care and challenges the assumption that high-quality care for all citizens requires massive financial investment. The evolution of the Cuban health care system since the revolution thus has implications for the U.S. health care system; specifically, it suggests that the equitable distribution of health care services in the United States requires a national health insurance and service delivery system. PMID- 2315761 TI - A group orientation program for families of newly admitted cancer patients. AB - Diagnosis and treatment of cancer is traumatic for patient and family, and hospital admission is the climax of the crisis. The authors describe a program in which social workers and former cancer patients orient families to a cancer center at the time of patient admission. The goals of the program are to lessen anxiety and increase mastery at this entry point into the medical system. No medical information is given during the group sessions. Content includes information on hospital facilities, treatment equipment, common feelings that cancer patients and their families experience, ways that family members can support the patient, and the roles of various hospital staff. The sessions also serve as a screening tool for the hospital to identify families that may need additional intervention. The program lessens the trauma for patients and their families, engages family members in treatment, and facilitates positive interactions between the hospital staff and members of patients' support networks. PMID- 2315762 TI - Why every social worker should be challenged by AIDS. PMID- 2315763 TI - Does social work education make a difference? AB - To test the hypothesis that state employees with social work education are better prepared for social work positions than are their colleagues without such education, data were collected in five areas, using different instruments and approaches. The data sets were scores on state merit tests for family service workers, employees' quality assurance scores, ratings of employees from supervisors, measures of employees' commitment to social work values, and measures of employees' confidence in their educational preparedness. Overall, employees with social work degrees, either bachelor's or master's, were better prepared than were those without social work degrees. PMID- 2315764 TI - Organizational structure and client advocacy: lessons from the 1980s. PMID- 2315765 TI - Tobacco: the neglected addiction. PMID- 2315766 TI - The SHARP carwash: a community-oriented work program for substance abuse patients. PMID- 2315767 TI - Social work and mental illness. PMID- 2315768 TI - Ability of practitioners to estimate client acceptance of single-subject evaluation procedures. AB - Practitioners' ability to estimate client acceptability of treatment evaluation procedures was investigated. Practitioners were able to predict accurately their clients' favorable responses to the use of single-subject procedures. The results lend support to those advocating continued research into variables affecting the use of systematic evaluation procedures by social work practitioners. PMID- 2315769 TI - What you see... PMID- 2315770 TI - Medications obtained in Mexico by patients in southern New Mexico. AB - Many health care providers practicing near the border between the United States and Mexico have serious concerns about their patients' using medications obtained in Mexico. Despite these concerns, the extent of this problem is not known. A survey administered in a publicly funded rural clinic and an urban private practice in southern New Mexico assessed this problem. The survey revealed that 87% of the rural clinic patients and 6% of the urban private practice patients had purchased medications in Mexico within the past two months. Further, 91% of the clinic patients and 56% of the private practice patients stated that they had, at some time, used medications from Mexico. Although many of these medications are fairly innocuous, their easy accessibility and lack of regulation can lead to serious health hazards. PMID- 2315771 TI - Antibiotic prophylactic uterine lavage in cesarean section: a double-blind comparison of saline, ticarcillin, and cefoxitin irrigation in indigent patients. AB - The purpose of this present study was to determine whether intraoperative antibiotic uterine irrigation was effective in reducing febrile morbidity (Part 1), and to determine whether ticarcillin disodium (Ticar) or cefoxitin sodium (Mefoxin) was the more effective solution (Part 2). The indications for cesarean section had an effect on febrile morbidity. In patients having nonelective cesarean section, febrile morbidity was high, occurring in 62.7% of the saline control group and 32.9% of those receiving ticarcillin disodium irrigation. In patients having elective cesarean section, febrile morbidity was lower (28% in the saline control group and 8.3% in the ticarcillin group [P less than or equal to .05]). Ticarcillin and cefoxitin were equal in reducing postoperative febrile morbidity. The use of prophylactic antibiotics, therefore, is indicated both in high-risk patients having nonelective cesarean section and in low-risk patients having elective repeat cesarean section. PMID- 2315772 TI - Spontaneous midbrain hemorrhage. AB - Spontaneous (nontraumatic) midbrain hemorrhage (SMH) is an uncommon condition whose diagnosis is greatly assisted by the use of cranial computerized tomography. Of 18 cases described in the English language literature, only two were diagnosed without the aid of CT. We report five cases of SMH in five normotensive patients. Vertical gaze palsies were noted in four patients, headache in four, pupillary dysfunction in four, mild hemiplegia in two, unilateral ataxia in two, and unilateral asterixis in one. The diagnosis of SMH had not been considered before CT scanning in any of these patients. All patients had partial to complete recovery. Cerebral angiography in each case showed no abnormalities in the area of the hemorrhage. PMID- 2315773 TI - Fine needle aspiration and frozen section of salivary gland lesions. AB - This report examines the role of fine needle aspiration (FNA) and frozen section (FS) examination in the management of salivary gland lesions, and is based on a review of 58 cases. FNA specimens were first classified as nonneoplastic, or as benign or malignant neoplasms. Identification of specific morphologic type of neoplastic lesions was attempted. Overall accuracy for assigning cases was 86%. Specific accuracy (histologic type of neoplasms predicted by FNA) was 72%. No inflammatory lesion was incorrectly diagnosed as neoplasm. Eight patients with histologically documented neoplasm had aspirates classified as nonneoplastic because the sample obtained was not representative. These data indicate that FNA is a highly specific method for identifying benign and malignant neoplasms. Applications of salivary gland FNA include (1) identification of nonneoplastic lesions that may respond to nonsurgical management, (2) identification of neoplasms that represent lymph node metastases rather than primary lesions of the salivary gland, (3) preliminary identification of lymphomas, and (4) preliminary separation of benign and malignant neoplasms. PMID- 2315774 TI - Computerized tomographic appearance of renal cysts after extracorporeal shock wave lithotripsy. AB - We identified cysts in five kidneys of four patients who had lithotripsy. Three of these kidneys were evaluated with CT scans the day before and the day after lithotripsy and showed no change. The other two kidneys were studied by CT only after extracorporeal shock wave lithotripsy; hemorrhage was shown in one and cyst wall thickening in the other. PMID- 2315775 TI - HIV testing: the legal balance between individual and societal rights. AB - Testing for the presence of human immunodeficiency virus (HIV) antibodies creates a legal conflict between the individual's right to autonomy and privacy versus society's right to control the public health. A body of laws exists to address these conflicting rights. These laws, however, must evolve so as to strike a better balance between what society has a right to know and the individual's right to personal autonomy and privacy. Appropriate statutes should recognize that a legitimate need may arise for a physician to disclose otherwise confidential testing data to the spouse and other intimate sexual partners of an HIV-infected patient. PMID- 2315776 TI - Three ways of knowing in clinical medicine. PMID- 2315777 TI - Medicine in Budapest. PMID- 2315778 TI - Current challenges in house office training. PMID- 2315779 TI - Chylothorax in a patient with AIDS and Kaposi's sarcoma. AB - We have described the case of a patient with AIDS in whom a chylothorax developed, probably as a result of lymphatic obstruction from KS. This case emphasizes that the loss of proteins, fats, and lymphocytes into chylous pleural effusions can be particularly devastating in AIDS patients, who have profound nutritional problems and a marked depletion in the level of helper T-lymphocytes. PMID- 2315780 TI - Bilateral protrusio acetabuli in sickle cell anemia. AB - Extreme bilateral protrusio acetabuli is an unusual complication of hematologic disease. We have described a patient with sickle cell anemia who had this complication probably as a result of osteopenia. Thus sickle cell anemia should be added to the list of potential causes of protrusio acetabuli. PMID- 2315782 TI - Delayed diagnosis of a foreign body in the spinal canal. AB - The absence of neurologic deficit does not preclude the diagnosis of stab wound injury of the spinal cord. Adequate radiologic examination is fundamental in detecting retained foreign bodies. Surgical extraction of foreign bodies is indicated to avoid infection and myelopathy. PMID- 2315781 TI - Intra-abdominal mesenteric desmoid tumor. AB - We have presented a case of mesenteric desmoid tumor, with analysis of 21 such cases previously reported in Japan. PMID- 2315783 TI - Cardiopulmonary abnormalities after smoking cocaine. AB - We recently treated a young man who had chest pain after smoking "freebase" cocaine. Pneumomediastinum was diagnosed, and the electrocardiographic changes that developed were characteristic of coronary artery spasm. Although pneumomediastinum has been linked to "freebasing," we believe electrocardiographic abnormalities in this situation have not been previously reported. PMID- 2315784 TI - Thallium-201 scintigraphy in the diagnosis and management of myocardial sarcoidosis. AB - We have described three patients with clinical evidence of myocardial sarcoidosis to illustrate the utility of thallium-201 scintigraphy in demonstrating the myocardial lesions. Both the symptomatic and asymptomatic individuals studied showed the characteristic "reverse redistribution" phenomenon. No abnormalities were seen during the exercise phase of the thallium study, but myocardial defects were detected in each patient when repeat studies were obtained at rest six hours later. Steroid therapy resolved the defects in each case. We propose thallium-201 scintigraphy of the heart as a safe and useful tool for documenting myocardial involvement in sarcoidosis and following the effects of therapy. PMID- 2315785 TI - Conn's syndrome with rhabdomyolysis mimicking deep vein thrombophlebitis. AB - We have reported a case of Conn's syndrome, with pain, tenderness, and swelling of the calf mimicking deep vein thrombophlebitis. The symptoms were associated with sever hypokalemia and rhabdomyolysis, and these findings subsequently explained by primary aldosteronism, which was cured by adrenalectomy. PMID- 2315786 TI - Haemophilus influenzae meningitis in an adult with initially normal cerebrospinal fluid. AB - We have described an adult patient with signs and symptoms of bacterial meningitis who had an initially unremarkable cerebrospinal fluid examination, but then had development of fulminant meningitis over the next 48 hours. Bacterial meningitis with normal CSF values has been previously reported in children, immunocompromised hosts, and alcoholics, and in patients with fulminant infections due to Neisseria meningitidis. We recommend that all patients with signs and symptoms compatible with bacterial meningitis and with normal results of CSF examination have close follow-up clinically over the next 48 hours with consideration of repeating the lumbar puncture. PMID- 2315787 TI - Diverticular disease of the appendix. AB - We have discussed a case of appendiceal diverticulitis diagnosed at laparotomy, and reviewed the histologic and clinical findings. Although infrequently encountered, appendiceal diverticulitis must be entertained in the differential diagnosis of pain in the right lower quadrant, especially in the adult patient. PMID- 2315788 TI - Aspergillus endocarditis: cure without surgical valve replacement. AB - We have reported a case of fungal native valve endocarditis due to Aspergillus sp in which cure was effected by medical therapy alone. An infected sternectomy wound from a previous aortic valve replacement was considered a contraindication to surgery. PMID- 2315789 TI - Torulopsis glabrata fungemia in a diabetic patient. AB - We have presented a case of a stable diabetic outpatient who had an acute illness that proved to be Torulopsis glabrata fungemia responsive to amphotericin B therapy. Her only apparent additional predisposition was a nonobstructing renal calculus. Fungemia with this organism in an outpatient is most unusual. T glabrata should be an additional consideration in outpatient as well as inpatient illnesses, especially in diabetic women. PMID- 2315790 TI - Dilutional acidosis. AB - Rapid, extreme expansion of the extracellular fluid with solutions devoid of acid or alkali theoretically can produce a metabolic acidosis, due to buffer dilution. This phenomenon has previously been demonstrated only in experimental animal studies. We have reported what we believe to be the first documented case of hypobicarbonatemia and metabolic acidosis consequent to massive saline infusion, other causes having been excluded. PMID- 2315792 TI - Successful pregnancy in a patient with a double inlet left ventricle treated with a septation procedure. AB - Because of improved medical and surgical care, women with univentricular hearts may live to enter the reproductive years and become pregnant. Pregnancy in a woman with a history of a univentricular heart treated successfully with a septation repair can follow a favorable course if she is acyanotic without functional or cardiovascular compromise. PMID- 2315791 TI - Primary Vibrio vulnificus sepsis in Kentucky. AB - Vibrio vulnificus is associated with infection acquired during contact with sea water or with seafood, and is seldom suspected by physicians in noncoastal states. The ease of transportation of fresh raw seafood has facilitated this organism's capacity to produce disease in geographic areas in which it was previously unseen. We have reported a case of fatal Vibrio vulnificus sepsis acquired from ingestion of fresh oysters in the inland United States. PMID- 2315793 TI - Hypertrichosis of the eyelashes associated with interferon-alpha therapy for chronic granulocytic leukemia. PMID- 2315795 TI - The challenge of pelvic inflammatory disease. PMID- 2315794 TI - Fatal lithium toxicity during a religious fast. PMID- 2315796 TI - We need more accurate data on the causes of sickness and death. PMID- 2315797 TI - The effect of plasma volume expansion on uteroplacental blood flow in hypertensive pregnancies. AB - The effect of plasma volume expansion on uteroplacental blood flow was investigated in 20 hypertensive women in the 3rd trimester of pregnancy by measuring the radioactivity in the region of the placenta with a gamma camera after an intravenous injection of indium-113. Despite a significant increase in plasma volume there was no change in maternal blood pressure or in uteroplacental blood flow. This suggests an autoregulation of both blood pressure and uteroplacental blood flow. PMID- 2315798 TI - [The prevalence of Chlamydia trachomatis infections in new patients at the Infertility Clinic, UOFS, Bloemfontein]. AB - Chlamydia trachomatis is a common sexually transmitted agent causing infertility. Routine screening tests or empirical antibiotic treatment of infertile couples may be justified by the prevalence of this organism. In this study the female partner of 40 consecutive infertile couples was investigated. As a screening test direct immunofluorescence (DIF) was performed on fixed smears from endocervical swabs. Of a total of 40 specimens, 11 (27.5%) were positive, 25 (62.5%) were negative and 4 (10.0%) were equivocal. DIF was repeated on smears from 3 of the last 4 patients and all 3 specimens were positive for C. trachomatis. One patient was lost to follow-up and excluded from the study. Of a total of 39 specimens the final results yielded 14 (35.9%) positive and 25 (64.1%) negative. Statistical analysis showed no correlation between the clinical history and the presence of C. trachomatis infection. PMID- 2315799 TI - The taking of adequate cervical smears. AB - In order for cytological examination of a cervical smear to be an adequate method of screening for pre-invasive lesions, the smear must contain both squamous and endocervical cells. Figures obtained for 1988 indicated that in South Africa 45% of smears do not contain endocervical cells. The study reported, in which the same patients were compared in successive years but using different techniques, showed that with the use of biomedically designed tools 98.3% of smears can be classified as adequate. PMID- 2315800 TI - Conservative approach to the management of pelvic inflammatory disease. AB - Clinical criteria and treatment protocols are outlined for 663 cases of mild, moderate and severe pelvic inflammatory disease (PID). Data on 176 patients requiring admission to hospital and who were treated conservatively with antibiotics are analysed. Criteria for operative intervention are outlined; only 1 patient required surgical intervention. The study suggests that, provided strict criteria are adhered to, conservative management of PID is both safe and effective and offers outlying hospitals and rural practitioners a plan of management that can be safely followed before resorting to referral to major centres. PMID- 2315801 TI - Use of indium-111-labelled platelets in black stroke patients. A pilot study. AB - Human blood platelets labelled with indium-111 oxine have been shown to accumulate on damaged vascular surfaces and abnormal platelet deposition has been demonstrated in the carotid arteries of white stroke patients. Gamma scintigraphy of the carotid and cerebral arteries of 5 black stroke patients and 5 age- and sex-matched controls using 111In-labelled platelets showed no abnormal accumulation indicative of carotid artery disease. PMID- 2315803 TI - Basic cardiopulmonary resuscitation techniques--national consensus achieved. AB - Successful management of a cardiac arrest demands immediate and appropriate action. Numerous different techniques for cardiopulmonary resuscitation (CPR) have been described, resulting in confusion among health care providers with respect to the use of different methods under different circumstances. Lack of adequate resuscitation skills and the need for proper training are well recognised. The Heart Foundation of Southern Africa, in recognising this need, organised this country's first National Basic CPR Symposium, followed by a National Workshop where official representatives of major CPR-promoting organisations critically analysed and reviewed contentious issues in basic CPR with a view to providing national guidelines. It was unanimously agreed that the recommendations of the National Workshop, as reported here, would stand as the consensus of opinion of the 33 major CPR-promoting organisations in this country. PMID- 2315802 TI - Are clinical differences between black and white stroke patients caused by variations in the atherosclerotic involvement of the arterial tree? AB - The differences in site and degree of atherosclerotic involvement of various vascular beds and their clinical significance are emphasised in a study of 304 black stroke patients. Detailed clinical examinations, computed tomography (CT), gated blood pool studies, echocardiography and ECG were performed and autopsy studies carried out. CT of the brain showed that non-haemorrhage, i.e. ischaemic lesions, accounted for 71.2% of strokes, a similar figure to that found in white stroke patients. However, carotid bruits (0.62%) and peripheral vascular disease (0.9%) followed by transient ischaemic attacks (1.9%) were found to be uncommon. Similarly, ischaemic heart disease (6.9%) appeared to be less common than the incidence in reported white stroke patients. In 30 patients who came to autopsy, the maximum degree of atherosclerotic stenosis of the extracranial carotid arteries was 21.7% of the lumen diameter. The differences in the site and degree of atherosclerosis in blacks not only give rise to differences in the clinical features of stroke patients but may have an important bearing on their investigation, management and prognosis. PMID- 2315805 TI - Colorectal cancer in blacks. PMID- 2315806 TI - Packed cell volume and venesection. PMID- 2315804 TI - Locked unifacet dislocation L3 on L4 vertebra. A case report. AB - Unifacet dislocation of the lumbar spine, without fracture of the posterior elements on the opposite side, is a rare injury. A patient with this injury at the L3/L4 level is described. A satisfactory outcome was achieved using open reduction and internal fixation with plate and intrapeduncular screws. PMID- 2315807 TI - Seasonal and nocturnal asthma in the tropics and subtropics. PMID- 2315808 TI - Childhood asthma--foods the trigger? PMID- 2315809 TI - Dissatisfaction of registrars in training at the University of Cape Town Teaching Hospitals. PMID- 2315810 TI - [Should medical research form an integral part of the undergraduate medical curriculum?]. PMID- 2315811 TI - Relevance of ancestral surname identification in pedigrees of Afrikaner families with familial hypercholesterolaemia. AB - Familial hypercholesterolaemia (FH) is more prevalent among Afrikaans-speaking individuals in South Africa then elsewhere. Founder effects have been suggested as an explanation. A study was undertaken that demonstrated ancestral links for a low-density lipoprotein receptor allele, haplotype No. 2, in the two lines of descent identified and 2 other known pedigrees with the same haplotype. Probable founder members for this haplotype are identified. These differ from the founder members assumed to be responsible for a majority of FH. A minor founder effect is suggested. Explanations are given for the apparent lesser prevalence of the second haplotype associated with FH. PMID- 2315812 TI - Methaemoglobinaemia due to accidental sodium nitrite poisoning. Report of 10 cases. AB - Nitrates and nitrites are widely used in the food and chemical industry. Poisoning with these agents may be potentially life-threatening as a result of the production of methaemoglobin. A group of 10 patients suffering from moderate to severe methaemoglobinaemia after accidental intoxication with a sodium nitrite salt is described. One patient died but the other 9 recovered rapidly. The low mortality rate was attributed to prompt diagnosis and institution of appropriate therapy with methylene blue and ascorbic acid. PMID- 2315813 TI - An assessment of registrars and their training programmes at the University of Cape Town Teaching Hospitals. AB - In order to describe the registrar population and to highlight their problems, a study using an anonymous questionnaire was conducted in August 1988 at the University of Cape Town Group of Teaching Hospitals. The average age of respondents was 32 years and the majority had family responsibilities (60% married, 41% with dependents). They had significant medical experience and postgraduate qualifications. Registrars work long hours (mean 66 +/- 13.7 h/wk), with duty shifts that can extend for up to 34 hours. Most of their time at work was devoted to patient care, with time for study and research virtually non existent. Although the majority (61%) felt that the 'registrar experience' was worthwhile, a significant proportion of respondents (45%) had considered leaving the rotation. The study revealed several shortcomings that need to be addressed if candidates of good calibre are to be attracted, academic standards are to be maintained and sufficient specialists produced to serve the needs of our population adequately. PMID- 2315815 TI - Is there a use for stabilised human serum in the treatment of Scoline apnoea? A case report. AB - Prolonged apnoea occurs occasionally after the routine use of suxamethonium chloride (Scoline). A case history is presented where the use of stabilised human serum (SHS) resulted in a dramatic reversal of this problem. Guidelines for the management of this condition with special reference to the use of SHS are discussed. PMID- 2315814 TI - Inappropriate antidiuretic state in long-term psychiatric inpatients. AB - To investigate the occurrence of an inappropriate antidiuretic state in a long term psychiatric inpatient population, 690 patients underwent serum sodium determination. Forty-four patients (6.4%) had levels less than 133 mmol/l. Fifteen of these patients could be investigated further and the biochemical findings in all were consistent with an inappropriate antidiuretic state. Evidence of previous episodes of water intoxication was found in 80% of these patients. Although more than one possible cause was present in most patients, the two factors most strongly incriminated in the pathogenesis of the inappropriate antidiuretic state were the drugs carbamazepine and hydrochlorothiazide. PMID- 2315816 TI - Colonoscopic diagnosis of ileocolic intussusception in an adult. A case report. AB - An elderly man was admitted to hospital with dull abdominal pain and marked weight loss. Ileocolic intussusception was shown on colonoscopy and later confirmed at laparotomy. The main feature was a caecal lipoma. A review of the subject and comparison with two other cases is included in the report. If the colonoscopy reveals a coil-spring polypoid mass, intussusception must be considered as a diagnosis in patients with abdominal pain. PMID- 2315817 TI - Entry of spermatozoa into the cervical mucosa and transmission of the AIDS virus. PMID- 2315818 TI - Public social welfare expenditures, fiscal years 1965-87. AB - The years from 1965 to 1976 were a period of great expansion in social welfare expenditures under public law. The entry of the Federal Government into the fields of health care and education was responsible for much of the growth in the first part of this period; high inflation produced increased spending in the later years. From 1977 to 1987, the rate of growth in social welfare spending slowed considerably. In fact, since 1983 the dominant characteristic of such expenditures has been their stability. Although the amount of money spent was higher in each year, little change occurred in the relative size or the apportionment of the funds. The 1987 expenditures continued this pattern. The total amount spent, $834.4 billion, represented an increase of 6.6 percent over the previous year. This amount equaled 18.8 percent of the gross national product. In constant dollar terms, the increase from 1986 to 1987 was 1.7 percent. The Federal Government provided 60-62 percent of all social welfare funding from 1980 to 1986. In 1987, this share fell slightly--to 59.9 percent. The programs for social insurance, public aid, veterans, and housing were primarily Federally funded, while education was largely a State and local responsibility. Governments at all levels spent 53.4 percent of their funds for social insurance purposes in 1987, slightly more than in 1986. However, the experience at different levels of government varied considerably. Federal spending increased 2 percent as a percent of all Federal expenditures, while State and local spending decreased about 1 percent. PMID- 2315819 TI - Investment of Social Security reserves in three countries. AB - The current buildup of the U.S. Social Security Trust Fund has caused speculation about both the potential consequences of the buildup under different policy objectives and the fund's management. As is often the case, the search for precedents under similar circumstances abroad has been quite extensive on the part of legislators and U.S. experts in the field of financial policy. This article summarizes the experiences of Canada, Japan, and Sweden--all of whom have accumulated large trust fund reserves--with a focus on their investment policies. Trust fund investments in the three countries are similar as to types of investments, but the pattern of distribution of these investments varies widely from one country to another. PMID- 2315820 TI - Endoscopic injection sclerotherapy using a transparent overtube with intraluminal negative pressure (np-EIS) for esophageal varices. AB - Endoscopic injection sclerotherapy (EIS) using the transparent overtube (OT) method can be conducted safely and easily not only in elective esophageal varices but also in emergency cases because of the ability to obtain a good field of view and fixation of the varix. However, application of the OT method is limited because intravariceal injection into small varices through the slit of the OT is impossible. We devised a technique to apply the OT method to small varices by utilizing negative pressure in the OT (np-OT method). By using negative pressure, EIS with a transparent overtube is now suitable for all grades of esophageal varices, and the accuracy of puncture in EIS has been improved. Injection of the target area was successful in all cases. The rate of intravariceal injection has also been improved (47% in low-grade varices) because injection of all sites was possible. We call EIS by the np-OT method "np-EIS". PMID- 2315821 TI - Bacteremia after injection of esophageal varices. AB - Elective sclerotherapy for esophageal varices produces bacteremia in 4% to 53% of patients. The clinical importance of this phenomenon is uncertain. This study was undertaken to re-assess the incidence and clinical relevance of post sclerotherapy bacteremia. Blood cultures were taken prior to and at 5 min and 4 h after endoscopy in 50 patients for whom sclerotherapy was planned. In the 41 patients in whom varices were injected, positive cultures were obtained 5 min after sclerotherapy in only 4 patients (10%) and all but 1 patient had other possible causes of bacteremia. After 4 h, all blood cultures were sterile. No infective complications were identified. Bacteremia appears to be an infrequent and transient event after elective sclerotherapy. Only patients with prosthetic heart valves or endocardial abnormalities require antibiotic prophylaxis. PMID- 2315822 TI - Large-bile-duct stones--extracorporeal piezoelectric lithotripsy as adjuvant measure for endoscopic basket extraction. AB - Extracorporeal piezoelectric lithotripsy (EPL) was performed in 12 patients with large-bile-duct stones and intrahepatic stones. The Piezolith 2300 lithotripter (Wolf, Knittlingen, FRG) was used in all patients in whom routine endoscopic approaches for removal of the calculi had failed or were considered inappropriate because of large stone size or difficult localization. In 9 of the 12 patients the stones were fragmented. Complete stone clearance from the bile ducts was obtained in 8 of 10 patients by EPL alone or combined with one of the following: endoscopic extraction, mechanical lithotripsy or installation of solvents. Adjuvant EPL in conjunction with endoscopic therapy increased the success rate of nonsurgical treatment for bile duct stones from 73% to 95%. No clinically significant side effects or complications were noted. PMID- 2315823 TI - Pancreatic and biliary pressure changes during ERCP. AB - Injection of contrast is a prerequisite for endoscopic retrograde cholangiopancreatography. Such injection into the biliary and pancreatic duct systems may require considerable force. This paper reports the changes in pressure that result within the duct systems and highlights the significant pressure rise that occurs within the pancreatic duct. PMID- 2315824 TI - Endoscopic dilation of colonic postoperative strictures. AB - After the use of surgical staplers had become widespread, the number of colonic postoperative stenoses was observed to have increased. Nevertheless, the clinical relevance of this observation is minimal since only 2-5% of the patients complain of chronic constipation or obstruction symptoms. In such cases medical therapy is somewhat troublesome, and surgical treatment always implies a major operation. Endoscopic dilation has proved to be a reliable, simple, and safe therapeutic alternative. Forty-two patients with evidence of stenosis of either colocolic or colorectal anastomosis underwent mechanical or pneumatic dilation in our unit: 19 patients with a temporary diverting stoma were dilated before the colostomy was removed; in the remaining 23 cases, treatment was given according to the patients' symptoms or because it was not possible to pass the anastomosis with an endoscope. The overall failure rate was 2.4%, and no morbidity or mortality was found. When the percentages of patients successfully treated in one session alone were compared (76.9% versus 51.8%), balloon dilation was found to be more effective than bougienage. In our opinion, endoscopic dilation represents the mainstay of treatment of colonic anastomotic strictures, with surgery being reserved for the rare failures, when recurrence of cancer should be suspected. PMID- 2315825 TI - Bronchoscopy in severe blunt chest trauma. AB - Extended lesions of the lung parenchyma are often seen in association with blunt chest trauma. Blood aspiration, atelectasis and the formation of bronchopleural fistulae can lead to early respiratory deterioration and the development of severe post-traumatic complications (pneumonia, acute respiratory distress syndrome). Diagnostic and therapeutic bronchoscopy is essential on admission. This procedure helps to estimate the severity and extent of parenchymal lesions even before chest X-ray signs are noted. Bronchoalveolar lavage is needed for removal of aspirates. In our study bronchoalveolar lavage on admission reduced bacterial contamination and pneumonia in comparison to patients not lavaged. A new method for closure of bronchopleural fistulae is described. Fibrin instillation after balloon catheter occlusion leads to a significant reduction of tidal volume loss (greater than 50% in average). PMID- 2315826 TI - Percutaneous endoscopic laser lithotripsy of retained stones in the left hepatic duct. The role of the surgeon. AB - A 35-year-old woman with a retained stone in a branch of the left hepatic duct was referred to us. The stone was discovered on the postoperative T-tube cholangiogram. A flexible ureteroscope was introduced into the duct, under fluoroscopic and direct endoscopic vision and the pulse dye laser was used successfully to disintegrate the calculus. The postoperative course was uneventful. We suggest that in certain selected cases, the pulsed dye laser might be useful in disintegrating stones sited in difficult positions. PMID- 2315827 TI - Cholecystocolic fistula: an unusual presentation and diagnosis by endoscopic retrograde cholangiopancreatography. AB - This report describes a patient with a cholecystocolic fistula whose presentation was unusual because it lacked the signs and symptoms that suggest biliary disease (abdominal pain, food intolerance, and belching) and because the fistula was not visualized on barium enema but was apparent on endoscopic retrograde cholangiopancreatography after incidental pneumobilia discovered on ultrasound directed our attention to the biliary tree. A previous Billroth II with vagotomy may have predisposed to the development of the fistula. PMID- 2315828 TI - Clinical correlates of erythropoiesis in chronic subdural hematoma. AB - Histologic investigation was performed in 38 out of 224 chronic subdural hematomas treated at our institution from 1978 to 1988. Nucleated red blood cells were found in 33% of the chronic subdural membranes examined. Additional sections were examined in 14 of these 38 patients, revealing erythroblasts in 57%. The clinical course and radiographic findings in the patients whose membranes contained erythroblasts were compared with those whose specimens did not. Neither history, presentation, size of hematoma, nor postoperative recovery differed from one group to the other. By comparing histologic and clinical findings, we are able to conclude that the production of erythrocytes by chronic subdural membranes is of no surgical significance. PMID- 2315829 TI - Estimation of intracranial pressure using computed tomography scan findings in patients with severe head injury. AB - The relationship between initial intracranial pressure and the findings of the first computed tomography scan on admission was assessed in 100 consecutive moderate-to-severe head injury patients using a method of multiple regression analysis. Intracranial pressure was measured through a slender subarachnoid catheter with a transducer. Thirty-nine checkpoints of computed tomography findings, including a shift of midline structure, the status of ventricles or cisterns, and the amount of subarachnoid hemorrhage, were investigated. The results were as follows: (1) The computed tomography findings that contributed to estimating intracranial pressure were the appearance of cisterns, the size of a subdural hematoma (number of slices), ventricular size, status of subarachnoid hemorrhage, status of cerebral contusion, magnitude of midline shift, and ventricular index, in that order. (2) Approximately 80% of predicted cases of intracranial pressure were included within the range of measured intracranial pressure +/- 10 mmHg. When the predicted intracranial pressure was less than 30 mmHg, the discrepancy between both intracranial pressures was small. It is concluded that an equation using several computed tomography findings gives a reasonably accurate intracranial pressure for the initial stage of severe head injury. PMID- 2315830 TI - Ultrastructural cerebrovascular changes in a model of subarachnoid hemorrhage in baboon based on triple cisternal blood injection. AB - In a subarachnoid hemorrhage model in the baboon, achieved through three cisternal blood injections with 1-day intervals, the cerebral arteries were dissected out 7 days after the first blood injection for electron microscopy All the animals showed ultrastructural changes in the cerebral arteries: two with severe, one with moderate, and three with mild alterations in the vessel walls. The most constant findings were seen in the muscle cells of the media layer. Fragmentation of the nuclei was frequently observed together with cytoplasmic vacuoles. Scattered groups or single degenerated muscle cells were also noted. In the intima the changes included rounding of the nuclei along with the appearance of cytoplasmic vacuoles. Desquamation or flattening of the endothelium and loss of tight junctions were encountered in some vessel areas. Degenerating mitochondria were a common finding. PMID- 2315831 TI - Treatment of hemispheric collapse and herniation beneath the falx in a case of shunted hydrocephalus. AB - A successfully treated case of inversion and herniation of a cerebral hemisphere beneath the falx is reported. This condition resulted from large subdural hematomas as a complication of shunting in advanced hydrocephalus. The subdural collections were evacuated gradually while ventricular cerebrospinal fluid was replenished through the externalized ventricular catheter. The patient showed substantial recovery of neurological function. Tolerance of such massive cerebral herniation demonstrates a remarkable ability of the thin hydrocephalic cortical mantle to function after extreme distortion. PMID- 2315832 TI - Granulomatous angiitis of the nervous system: a case report of long-term survival. AB - In 1977, a 61-year-old man developed an occipital hemorrhage, and a biopsy specimen revealed granulomatous angiitis of the nervous system. No concurrent infection or systemic vasculitis was present. After initial treatment with steroids and cyclophosphamide, the patient did well on chronic steroids alone for 4 years. He then independently stopped taking the steroids and suffered a second hemorrhage. Steroids were reinstated, and he did well for 3 more years before he experienced a third hemorrhage. Intravenous steroids were given acutely and tapered to a chronic maintenance dose. Although granulomatous angiitis of the nervous system usually causes death within weeks to months of the appearance of symptoms, the patient is still alive more than 12 years since the tissue-proven diagnosis. This unusually long survival is attributed to the continued use of steroids, even when the patient is asymptomatic. PMID- 2315833 TI - Alkaptonuric ochronosis and multiple intracranial aneurysms. AB - Alkaptonuric ochronosis is a heritable disorder of tyrosine metabolism, with various systemic abnormalities related to pigment deposition and degeneration of collagen and other tissues, including the heart and aorta, though no cerebrovascular abnormalities have been reported. The authors report a patient with alkaptonuric ochronosis and multiple intracranial aneurysms presenting with subarachnoid hemorrhage. The ruptured aneurysm was surgically treated, with a satisfactory outcome. In view of the well-known association of other connective tissue disorders with intracranial aneurysms, a potentially causal relationship is suggested between cerebral aneurysms and alkaptonuric ochronosis. PMID- 2315834 TI - Transcerebellar thrombectomy for the successful clipping of thrombosed giant vertebral artery-posterior inferior cerebellar artery aneurysm: case report. AB - The operative technique used for a thrombosed vertebral artery-posterior inferior cerebellar artery aneurysm that was treated by combined transcerebellar (petrosal surface) thrombectomy and neck clipping is presented. Transcerebellar thrombectomy permitted the successful clipping of this thrombosed vertebral artery-posterior inferior cerebellar artery aneurysm via the cerebello-medullary cistern. PMID- 2315836 TI - Balloon needle for the atraumatic transcortical ventricular approach: technical note. AB - We have designed a double-lumen inflatable needle for the atraumatic dissection of brain substance. This balloon needle has been successfully used for the ventricular approach in brain grafting procedures to obtain a rounded corticotomy with a diameter of 1.5-2 cm in the treatment of Parkinson's disease. PMID- 2315835 TI - Intracranial nonspecific inflammatory granuloma. AB - A case of nonspecific inflammatory granuloma arising from the dura mater near the hypoglossal canal is reported. A 38-year-old woman developed an isolated left hypoglossal nerve palsy. Computed tomography and magnetic resonance imaging demonstrated an enhanced tumorous lesion at the inner orifice of the left hypoglossal canal. Skull x-ray was normal, and cerebral angiography showed no vascular abnormalities. Examination of the cerebrospinal fluid showed mild pleocytosis with a predominance of lymphocytes. Systemic examination revealed no abnormalities. The tumor was removed completely and pathologic investigation revealed that it was an inflammatory granuloma. The patient's history and laboratory data, however, failed to suggest the underlying disease, and histopathologic examination did not indicate any special type of granuloma. Therefore, the lesion was diagnosed as a nonspecific inflammatory granuloma. PMID- 2315837 TI - Ethical and medical/legal problems in Chile. PMID- 2315838 TI - Needle size for puncture of a Rickham reservoir. PMID- 2315839 TI - [T-staging of tongue and mouth floor tumors: comparison of ultrasonography and computerized tomography]. AB - A comparison was made between the pretherapeutic CT and ultrasound findings of 43 patients with tumors of the oral tongue and the floor of the mouth. Two tumors of the edge of the tongue (T1) each were not diagnosed by computed tomography and by sonography. In three cases a more precise determination of the tumor size was achieved by sonography. In 25 out of 38 cases the contrast between tumor and sound tissue was better in the sonographic image. The reduction and regressive modification of the tumor following to radiotherapy could be observed in eleven cases. Despite the benefits of sonographic investigation in this area due to the excellent contrast without any need of contrast media, the good availability and the absence of metal and movement artefacts, this method is not able to replace computed tomography. The most important disadvantages of sonography were found to be the incapability to show osseous erosions and the restricted or lacking possibility to assess the parapharyngeal and the retropharyngeal area. PMID- 2315840 TI - [Radium contact irradiation of vocal cord carcinoma--a possible treatment method?]. AB - In the course of the use of carrier- bounded radioactive substances for the treatment of the vocal cord carcinoma, 113 patients with a vocal cord carcinoma were treated with radium contact irradiation after thyroid cartilage windowing at the ENT University Clinic Essen. The period of study extended from 1972 to 1983. 88,6% of the patients with vocal cord carcinoma, who showed a typical localisation for radium contact irradiation, became recurrence-free. About 88,0% of the patients, who were led through an irradiation treatment of extended indication, became recurrence-free. A normal vocal function was achieved in 71,7% of all cases. PMID- 2315841 TI - [Functional changes in the lower urinary tract after irradiation of cervix carcinoma]. AB - 104 patients submitted to primary irradiation for cervix carcinoma were examined by means of urodynamic methods of diagnosis in order to investigate the functional changes of the lower urinary tract induced by therapy. 34 patients could be examined prior to therapy, 19 and 12 patients, respectively, were examined six and 18 months on an average after the treatment. Another group of 70 patients had retrospective check-up examinations with average intervals of five and ten years. Hydronephrosis occurred only as a late result after more than six years in 12% of the irradiated women. The incidence of residual urine, significant bacteriuria, and disturbed sensory function of the bladder was not important. All patients were incontinent two years after the irradiation; 60% of the cases of incontinence were due to the bladder and 40% to the urethra. The increase of urgency incontinence is possibly caused by a radiofibrotic reaction of the bladder, as is shown by correspondent cystometric alterations: the bladder tonicity increased, whereas the bladder capacity decreased. These alterations were only partially reversible. The stress incontinence, however, was found already before the treatment. The maximum urethral closing pressure, which often indicates incontinence due to the urethra, was not modified by the irradiation. An increased stress incontinence, probably caused by advanced age, was found only after six years or later. The problems resulting from functional changes should be taken into consideration in the course of post-therapeutic care, i.e. the patients concerned should be given instructions for a regular bladder training. PMID- 2315842 TI - [A simple method for MRI-assisted radiotherapy planning in brain tumors]. AB - A simple method for radiation therapy planning of brain tumors is presented. Therapy portals of midline tumors can easily be determined by comparing sagittal MRI scans with the lateral simulator radiograph. By addition of appropriately processed MR-tomograms a similar planning is possible for parasagittal tumors. Digital data exchange between different operating systems is not necessary with our simple method, problems with varying input/output standards and expensive hardware requirements are thus avoided. PMID- 2315843 TI - [Esthesioneuroblastoma--treatment of recurrences using the remote-control afterloading technic. A case report]. AB - At the Radiological Hospital of the Heidelberg University, one patient with a local recurrence of an esthesioneuroblastoma situated on the left-hand side of the skull base was treated between February 11 and March 18, 1986, by an afterloading contact therapy with curative intent. After preceding surgery and percutaneous radiotherapy, repeated local recurrences and locoregional lymph node metastases had occurred. The contact therapy was performed after adjusting an individual face mask in which the afterloading probe was placed and brought into its position in the tumor region. The irradiation scheme was based on the transformation of the source coordinates form the stereoscopic X-ray localization system into the coordinate system of the computed tomogram by means of X-ray tight reference points. The irradiation planning by computed tomography allows to optimize the arrangement of sources within the tumor region. The principles of the method as well as the treatment result are presented. PMID- 2315844 TI - The influence of electromagnetic interference and ionizing radiation on cardiac pacemakers. AB - Adverse effects of the ionizing and non-ionizing electromagnetic fields on five pacemaker models have been tested. The study consisted of three parts: 1. measurement of magnetic fields in a radiotherapy room (microtron MM14), 2. the application of non-ionizing electromagnetic fields on pacemakers in a test laboratory (1...1000 microT, 10...10000 Hz), and 3. the application of ionizing radiation of different types of radiotherapy devices on the pacemakers. The magnetic field strength in the microtron treatment room was found to be under 7.5 microT, which is one order of magnitude lower than the tolerance level obtained for the pacemakers in the test laboratory. All the tested pacemakers tolerated the ionizing radiation dose levels (less than 60 Gy) which are used in the radiotherapy. PMID- 2315845 TI - Biophysical investigations on L1210 mouse leukemia cells treated with activated cyclophosphamide metabolites: determination of selective properties of DNA interstrand and DNA-protein cross-linking mechanisms (alkaline elution and 31P NMR-spectroscopy) and some aspects of the combination drug and radiotherapy. AB - Dose-effect relationships have been studied by using L1210 mouse leukemia cells treated with the activated cyclophosphamide derivatives 4-hydroperoxy cyclophosphamide and 4-sulfido-cyclophosphamide. The combined treatment of the cells with the drugs and irradiation with X-rays indicates synergistic effects, if the irradiation of the cells is performed four to six hours after the drug treatment. DNA-interstrand and DNA-protein cross-linkings have been determined by an alkaline elution procedure. The yield of cross-linkings has been monitoring by either the 3H-14C method or by a 31P-NMR Fourier spectroscopy analysis of the eluted substrates. PMID- 2315846 TI - Radioresistance of rat glioma cell lines cultured as multicellular spheroids. Correlation with electrical cell-to-cell-coupling. AB - Two chemically induced rat glioblastomas, RG2 and F98, were cultured as monolayers and as multicellular spheroids and subjected to Co-gamma-irradiation. In parallel, intercellular communication between cells was determined as electrical coupling between neighbouring cells using micro-electrode techniques. A third glioblastoma with known radiobiological response (9L) was assayed with respect to intercellular communication and included into this analysis. Electrical coupling was low for RG2, intermediate for F98, and high for 9L. Radioresistance of spheroids, as expressed in terms of the mean inactivation dose computed from the survival curves increased in the same direction (RG2: 2.4 Gy; F98: 5.1 Gy; 9L: 6.5 Gy). A comparison of these parameters demonstrates a correlation between solid tumor radioresistance and gap-junctional cell-to-cell communication, at least for the class of glioblastomas analysed in this study. PMID- 2315847 TI - Glycolytic changes after local hyperthermia in mouse liver and adenocarcinoma. AB - Glycolytic changes in an adenocarcinoma and in liver of C57B1 mice were determined for up to twelve hours after local hyperthermia at 43 degrees C for 30 min. The metabolites studied included glucose, glucose-6-phosphate, pyruvate, lactate, acetoacetate and beta-hydroxybutyrate. Both the glucose and glucose-6 phosphate levels decreased significantly in liver and tumour and remained low for up to twelve hours. The lactate levels increased slightly immediately after heating but were decreased at later times. However, the hepatic pyruvate levels decreased for up to two hours after heating but increased later reaching control levels. In both liver and tumour the levels of beta-hydroxybutyrate were significantly enhanced immediately after hyperthermia, whereas those of acetoacetate were lowered. PMID- 2315849 TI - [New models for nursing service]. PMID- 2315848 TI - The reaction of lymphatic component of hemopoiesis to fractionated irradiation and repeated bone marrow transplantation. AB - Mice were repeatedly subjected to individual doses of 60Co-gamma rays at intervals of four days up to total doses of 3, 6, 9, 12, 15, 18, 21 and 24 Gy. Under these conditions, signs of partial adaptation of the lymphatic component of hemopoiesis to conditions of repeated irradiations were found in mice which were given transplants of 10(6) nuclear cells of syngenetic bone marrow after each irradiation. Systematic findings of statistically significant differences in the values of the lymphatic hemopoietic component parameters studied between bone marrow recipients and animals subjected only to repeated irradiations were recorded after 24th day of experiment in mice which received total doses of 21 and 24 Gy. A positive influence of repeated transplantations in bone marrow recipients became manifested in these experimental groups already upon withdrawals made on day 4 after the last irradiation. A quite pronounced increase in the values of the bone marrow recipients' lymphatic hemopoietic component studied was then recorded upon withdrawals made on day 9 after the last irradiation. PMID- 2315851 TI - ["Evil in life"--a new popular disease. Interview by Jette Kingod]. PMID- 2315850 TI - [Greater Copenhagen's special plan is welcome]. PMID- 2315852 TI - [Cost containment aggravates the ethical dilemma. Interview by Jette Kingod]. PMID- 2315853 TI - [The nurse for the 90s. Interview by Grethe Kjaelgaard]. PMID- 2315854 TI - [We should have continuing education for the many. Interview by Mette Marie Davidsen and Grethe Kjaergaard]. PMID- 2315855 TI - [Education--countdown. Interview by Grethe Kjaergaard]. PMID- 2315856 TI - [The essence of nursing lies in home nursing]. PMID- 2315857 TI - [FTF: government's blind navigation without the necessary perspective. Interview by Kirsten Stallknecht]. PMID- 2315858 TI - [FTF organizations move up to negotiating table]. PMID- 2315859 TI - [New framework for Scandinavian cooperation]. PMID- 2315860 TI - [Radiology nursing. Patients need more than technically perfect images]. PMID- 2315861 TI - [Radiology nursing. Diagnostic imaging continuing education with professional identity]. PMID- 2315862 TI - [Newly created center for brain-damaged patients]. PMID- 2315863 TI - [Danish Nursing Council's sex discrimination]. PMID- 2315864 TI - [Patients choose nurse for themselves. Interview by Anne Vesterdal]. PMID- 2315865 TI - [12 years of cross-professional team work in childbirth in Herlev]. PMID- 2315866 TI - [Cholesterol level can be lowered]. PMID- 2315867 TI - [Physicians want to withhold research results. Interview by Mette Ellegaard]. PMID- 2315868 TI - [Heart transplantation as clinical routine practice]. PMID- 2315869 TI - [Evaluating the graft rejection reaction in endomyocardial biopsy]. AB - Transplant survival is the result of a balance between natural defence mechanisms and their suppression by drugs. A grading system of allograft rejection should characterize this equilibrium quantitatively. The system developed by McAllister evaluates graft rejection on a numerical scale ranging from 0 to 10. This scale enhances communication between the pathologist, surgeon and cardiologist. In our experience with more than 1000 biopsies of 80 patients the Texas scale is useful. PMID- 2315870 TI - [Toxoplasmosis in the heart transplant patient]. AB - Toxoplasmosis is a well-known problem under immunosuppressive conditions in cardiac transplant patients. In our series 12% of the patients (8 of 65) had clinical and/or serological signs of active toxoplasmosis. Due to its serious prognosis once the clinical process has started we favor a generous diagnostic interpretation of the serological results and a broad indication to drug therapy. PMID- 2315871 TI - [Long-term follow-up after heart transplantation]. AB - Actuarial survival rate two years after heart transplant in our patients is 90%. The most patients report excellent quality of life (NYHA I) and present definitely improved work load capacity as well as normal cardiac hemodynamic assessment two years after transplant. The major problems in the long follow-up of heart transplant recipients are accelerated coronary disease (graft atherosclerosis), arterial hypertension and renal function impairement. PMID- 2315872 TI - In vitro and in vivo effects of ribavirin on human respiratory epithelium. AB - The effects of ribavirin, a broad spectrum antiviral agent, on the structure and function of normal human nasal epithelium have been studied in vitro, as has also the in vivo effect of treatment with nebulised ribavirin on nasal mucociliary clearance of saccharin in four patients. Ciliary beat frequency was measured by a photometric technique, and changes in epithelial and ciliary ultrastructure were assessed by transmission electron microscopy. Ribavirin solution at the recommended concentration of 20 mg/ml had no adverse effects on ciliary activity in vitro; at concentrations of 50 mg/ml and above it slowed ciliary beating significantly and at 60 mg/ml caused ciliostasis associated with epithelial disruption. Nasal inhalation of ribavirin at 60 mg/ml for up to 20 minutes, however, did not slow nasal mucociliary clearance, nor did it adversely affect the ciliary beating or structure of nasal ciliated epithelium examined in vitro immediately after inhalation. PMID- 2315873 TI - Particle size of beclomethasone dipropionate produced by two nebulisers and two spacing devices. AB - An impactor method was used to assess the amount of beclomethasone dipropionate in particles less than 5 microns produced by two nebulisers (Pari Inhalierboy, Medix Traveller compressor with cirrhus nebuliser chamber) and two spacer devices (Volumatic and Nebuhaler). After nebulisation of 3 ml (150 micrograms) beclomethasone dipropionate the amount of drug in particles less than 5 microns was 16 micrograms (GSD 1.1) with the Pari Inhalierboy, and 27 micrograms (1.4) with the Medix Traveller with cirrhus nebuliser. This was less than the amount in particles less than 5 microns after three metered dose inhaler actuations (150 micrograms) from the Nebuhaler (58.2 (1) micrograms) or the Volumatic spacer (46.5 (1) micrograms). The greater amount of beclomethasone dipropionate in small particles with administration from a metered dose inhaler with a spacer device means that considerably more drug is likely to reach the airways than when the same dose is given by the two nebulisers studied. PMID- 2315874 TI - Diagnosis of congenital cystic adenomatoid malformation of the lung in newborn infants and children. AB - Seventeen patients were diagnosed as having congenital cystic adenomatoid malformation of the lung during 1970-88. One case was associated with congenital diaphragmatic hernia and the child died before operation. The other 16 children underwent successful surgery. The patients presented in one of three ways--with neonatal respiratory impairment (12 cases) requiring urgent diagnosis and treatment, with recurrent respiratory tract infections (3), and with pneumothorax (1). Diagnostic problems arose with the neonatal presentation. In four of the children laparotomy was performed for presumed diaphragmatic hernia; three of these children had right sided lesions. Congenital diaphragmatic hernia was excluded by contrast studies in a further two patients. Histological examination confirmed the diagnosis in all cases. The postoperative course was uneventful in all 16 patients. No long term impairment of pulmonary function was noted. PMID- 2315875 TI - Pulmonary sequelae in survivors of congenital diaphragmatic hernia. AB - Nineteen survivors of congenital diaphragmatic hernia repair were compared with age and sex matched control children six to 11 years after repair. All subjects were examined clinically and underwent lung function testing. The patients also had individual lung volumes assessed radiographically and had radionuclide (krypton-81 m, technetium-99 m macroaggregates) ventilation-perfusion (V/Q) lung scans. Four patients had pectus excavatum and two had mild scoliosis. Spirometric measurements were lower in the patients than in the control subjects but only the differences in peak expiratory flow and flow at 50% of expired vital capacity were significant. The radiographic left lung volumes in patients surviving left diaphragmatic repair were larger than expected at 49.3% (SD 2%), suggesting alveolar overdistension. V/Q scans showed a mismatch in the ipsilateral lung, mean Q (40% (7%] being significantly lower than mean V (47% (6%)). In seven patients who had required ventilation for four days or more perfusion to the ipsilateral lung was significantly lower (34% (6%)) than values for the 12 patients ventilated for less than four days (43% (6%)). Survivors of right diaphragmatic repair had a better outcome in terms of relative radiographic lung volumes and V/Q distribution. More severely affected children are now surviving repair of congenital diaphragmatic herniation, with residual pulmonary abnormalities that could produce functional impairment in adult life. PMID- 2315876 TI - Changes in hospital management of acute severe asthma by thoracic and general physicians in Birmingham and Manchester during 1978 and 1985. AB - Hospital management of acute severe asthma in 14 large hospitals in Birmingham and Manchester was audited in a random 20% of 1196 patients aged 15-45 years admitted in 1985. Of the 239 admissions randomised, 192 were suitable for study. Results were compared with those from a study in the same hospitals using the same methods in 1978. The age and sex of the patients and their smoking history, duration of asthma, and hospital attendance were similar in 1978 and 1985. A much smaller proportion of patients presented with symptoms of over seven days' duration in 1985 (8.5%) than in 1978 (26%). The inpatient management of asthma appears to have improved in both thoracic and general units, with more thorough functional assessments, more frequent performance of relevant investigations (arterial blood gases and peak expiratory flow rates) and more frequent use of recommended treatment (nebulised bronchodilators, oral and intravenous corticosteroids). Less difference was found in 1985 between units with a specialist thoracic interest and those without, though some differences remained in 1985 in monitoring of peak expiratory flow rate and arterial blood gases, outpatient prescribing, and follow up arrangements. Inhaled preventive medication was prescribed more frequently than in 1978. In 1985 there was a 56% increase in admissions for asthma. The proportion of severely ill patients was similar to that in 1978, but in the most severe functional grade mean arterial carbon dioxide tension was higher in 1985 and more patients were ventilated. Our results suggest that hospital management by thoracic and general physicians has improved over the period 1978-85. Patients presented earlier in 1985, though there seems to have been an increase in asthma of all grades of severity. PMID- 2315877 TI - Systemic amyloid associated with carcinoma of the bronchus. AB - An association of systemic amyloid with a squamous cell carcinoma of the bronchus is described. Amyloid may be associated with myeloma and neuroendocrine tumours but has not been described in squamous cell carcinoma of the bronchus. PMID- 2315878 TI - Significance of antibodies to cytoplasmic components of neutrophils. PMID- 2315879 TI - Pulmonary eosinophilia. PMID- 2315880 TI - Relation between small airways disease and parenchymal destruction in surgical lung specimens. AB - The relation between small airways disease and parenchymal destruction was investigated in lungs and lobes removed at surgery from 27 patients aged 15-70 years. Eight of the 27 patients were life-long non-smokers. The degree of small airways disease was assessed by semi-quantitative grading (SAD score) and by measuring diameter and wall thickness of membranous bronchioles. Parenchymal destruction was measured in three ways. Firstly, the number of alveolar attachments on membranous bronchioles per millimetre of circumference (AA/mm) was counted; the number of broken attachments was subtracted from the total AA/mm to give the numbers of intact attachments (normal AA/mm). Secondly, a point counting technique was used to give a destructive index (DI). Thirdly, the mean linear intercept (Lm) was determined. Total and normal AA/mm correlated negatively with the SAD score of membranous bronchioles (rs = -0.48 and -0.51) and with wall thickness (rs = -0.37 and -0.45) and DI correlated with wall thickness (rs = 0.5) and with the SAD score of respiratory bronchioles (rs = 0.53). Lm did not correlate with indices of small airway disease and total and normal AA/mm did not correlate with diameter. Multiple regression analyses showed that the correlation of total AA/mm with the SAD score of membranous and respiratory bronchioles and with wall thickness were not confounded by age or smoking. It is concluded that small airways disease is related to destruction of peribronchiolar alveoli, and it is postulated that small airways disease has a direct role in the causation of centrilobular emphysema. PMID- 2315881 TI - Reduced selenium in asthmatic subjects in New Zealand. AB - Selenium is an essential component of glutathione peroxidase, an enzyme that helps protect cells against oxidation damage and modulates the lipoxygenase pathway of arachidonic acid metabolism. Low selenium concentrations might therefore influence the inflammatory process in asthma by reducing the activity of glutathione peroxidase. Whole blood and plasma selenium concentrations and glutathione peroxidase activity have been measured in 56 asthmatic patients and 59 non-asthmatic control subjects in New Zealand, a country with a low dietary selenium intake and a high prevalence of asthma. When compared with control subjects the asthmatic patients had lower values for whole blood selenium concentrations (-4.9, 95% confidence interval -10.2 to 0.4 ng/ml) and glutathione peroxidase activity (-3.3, 95% CI -5.8 to -0.8 units/g Hb). There was a 1.9 and 5.8 fold increased risk of asthma in subjects with the lowest range of whole blood selenium concentration and glutathione peroxidase activity respectively (95% CI 0.6 to 5.6 and 1.6 to 21.2). Levels were lower in patients and control subjects without an atopic predisposition, but were not affected by prednisone use. Similar differences between the asthmatic and control subjects were not observed for selenium concentration or glutathione peroxidase activity measured in plasma, which reflects short term rather than long term selenium content. These findings are consistent with the hypothesis that low selenium concentrations may have a role in the pathogenesis of asthma in New Zealand. PMID- 2315883 TI - Location of the binding site "b" for lateral polymerization of fibrin. AB - We examined the location of the binding site "b" for lateral polymerization of fibrin using two fractions of normal human fibrinogen, a high-molecular weight fraction (so-called normal fibrinogen) and a low-molecular weight fraction which lacks the C-terminal half of one of its two A alpha chains, and Gly-His-Arg-Pro, a synthetic peptide that corresponds to the N-terminal sequence of human fibrin beta chain and binds specifically to the site "b". The amounts of the synthetic peptide bound to each of the low- and high-molecular weight fractions were 1 mol/mol and 2 mol/mol, respectively. The peptide delayed the clotting of fibrinogen by blocking the site "b", but did not inhibit thrombin at all. In the presence of the peptide, the high-molecular weight fraction did not form a normal coarse clot but a fine clot which was identical to that produced by the low molecular weight fraction. The identity of the two clots was judged from four different points: morphology, turbidity, elasticity and clotting velocity of fibrin. The results suggest that the site "b" is located within the portion of the fibrinogen molecule present in the high-molecular weight fraction, but not in the low-molecular weight fraction and that the site "b" plays an essential role in the lateral polymerization of fibrin. PMID- 2315882 TI - Recombinant human erythropoietin shortens the uraemic bleeding time without causing intravascular haemostatic activation. AB - Blood rheology and haemostasis have been investigated in 8 haemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). The aim was to elucidate the mechanism by which rHuEPO improves haemostasis, and to determine whether rHuEPO promotes intravascular coagulation. Investigations were performed before, and after 3 months of treatment. Haemoglobin and haematocrit rose significantly after rHuEPO (p less than 0.001) and there was a concurrent shortening of the bleeding time. No significant changes were observed in platelet aggregation, thromboxane generation, or platelet nucleotide content during the treatment period. Whole blood viscosity increased following rHuEPO (p less than 0.01), but plasma viscosity and red cell deformability were unchanged, as were markers of intravascular platelet activation and plasma levels of cross-linked fibrin derivatives. No patient suffered from thrombosis during the study period, and elevation of the haematocrit in uraemic patients up to 0.35 with rHuEPO did not appear to lead to intravascular coagulation. Shortening of the prolonged bleeding time in haemodialyzed patients following rHuEPO appeared to be due to the increase in circulating red cells, rather than to changes in platelet reactivity. PMID- 2315884 TI - Determination of the minimal concentrations of contact activation factors in deficient substrate plasmas required to assess accurately factor XII, factor XI, factor IX, and high molecular weight kininogen. AB - Using combined deficient plasmas prepared by passage of a deficient plasma over an anti-factor XI-monoclonal antibody column, we have determined the threshold concentrations of each coagulation factor of contact phase in factor-deficient substrate plasmas required to determine accurately the functional activities of factor XII, factor XI, factor IX and high molecular weight kininogen (HMWK). In order to reliably quantitate factor XI and factor IX activity levels, at least 20% factor XII and 20% factor XI, respectively, were required in the deficient substrate plasmas. In the assessment of factor XII activity, approximately 40% factor XI was required in the factor XII-deficient substrate plasma. On the other hand, only 11-12% factor XI or HMWK was required in the deficient substrate plasmas in the assessment of these two clotting factors. Our data emphasize that deficiencies of other clotting factors may reduce the apparent activity of the clotting factor in question if their concentration is rate-limiting in the clotting assay. PMID- 2315885 TI - Effect of warfarin on plasma and liver vitamin K levels and vitamin K epoxide reductase activity in relation to plasma clotting factor levels in rats. AB - Changes in plasma and liver vitamin K1 and vitamin K1 epoxide levels, liver microsomal vitamin K epoxide reductase activity, and plasma clotting factor II and VII levels were determined in rats after a single injection of warfarin (2.5 mg/kg, s.c.). The plasma and liver vitamin K1 levels gradually decreased after warfarin injection, attaining the lowest values at 2-3 hrs and remaining low for 48 hrs. They then returned to the control levels at 72 hrs. The changes in vitamin K1 epoxide levels were opposite, with an increase being seen soon after the warfarin injection, the highest values at 3 hrs and a gradual decrease to the initial levels occurring subsequently. The combined levels of vitamin K1 plus vitamin K1 epoxide, however, remained almost constant in both plasma and liver after the warfarin injection. The liver vitamin K epoxide reductase activity decreased to its lowest level soon after the injection and then gradually increased after 12 hrs, but the activity at 72 hrs was only about 30% of the initial activity. The plasma clotting factor levels gradually decreased after the injection, bottomed at 24 hrs and then began to increase, recovering almost to the initial levels at 72 hrs. A positive correlation was found between plasma and liver levels for both vitamin K1 and vitamin K1 epoxide, and the slope of the vitamin K1 epoxide curve was steeper than that for vitamin K1 in the warfarin treated rats. A similar positive correlation was found for both vitamin K1 and vitamin K1 epoxide after vitamin K1 injection in normal untreated rats, but the slope of the vitamin K1 epoxide curve was much shallower. These results suggest that warfarin inhibits vitamin K epoxide reductase and decreases blood clotting factor synthesis, thus increasing plasma and liver vitamin K1 epoxide levels. A vitamin K epoxide reductase activity one third of that in normal rats is sufficient to maintain normal reduction of vitamin K1 epoxide and synthesis of blood clotting factors. PMID- 2315886 TI - Anticardiolipin antibodies and thrombosis: buffer's influence on the detection and quantitation of anticardiolipin antibody measured by ELISA. AB - The influence of adult bovine serum (ABS) and fetal calf serum (FCS) on IgG anticardiolipin antibodies (ACA) levels measured by ELISA has been investigated. In control subjects the frequency of the optical density (O.D.) distribution was found to be non-gaussian. The O.D. of the 97th percentile was similar with both buffers, although the distribution of O.D. was statistically different (P less than 0.004). The slope of the dilution curves of two house standards as well as the curves obtained with reference standards were found to be very different depending on the buffer. In 55 consecutive patients with thrombotic events, recurrent fetal loss or auto-immune disorders, ACA positivity was also dependent on the way to express the data and the choice of the buffer: when O.D. values were read with their respective standard curves, IgG ACA positivity was 98% with FCS and 20% with ABS (P less than 0.001), but when the 97th percentile O.D. was considered, 40% were positive with FCS and 51% with ABS (n.s.). Furthermore 10 patients were found to be negative with FCS and positive with ABS and 4 others showed the inverse picture. Levels of positivity were also dependent on the buffer. These differences arise from the solution used to dilute the sera and not of that to block the plates. These methodological problems may explain some conflicting data found in the literature about the prevalence of ACA positivity. PMID- 2315887 TI - Factor VII activation and menopausal status. AB - The incidence of coronary heart disease (CHD) is higher in postmenopausal or oophorectomised women than in premenopausal women of the same age. The difference cannot be explicable in terms of conventional CHD risk factors. Since factor VII may be relevant to the pathogenesis of CHD, we have investigated the menopause related changes in factor VII activation in 228 healthy women aged 45-54 years. A standard factor VII clotting assay (FVIIc) and a factor VII antigen assay (FVIIag) were carried out on the same plasma samples. Both FVIIc and FVIIag levels were significantly higher in postmenopausal than in premenopausal women. Despite the strong correlation between the two assays (r = 0.80), the FVIIc/FVIIag ratio was positively and significantly associated with the menopause, suggesting that activated factor VII form might in part account for the high FVIIc levels in postmenopausal women. With respect to the type of menopause, the highest levels of both FVIIc and FVIIc/FVIIag ratio were found in women having undergone bilateral oophorectomy. These results suggest that raised factor VII coagulant activity may contribute to an increased risk of CHD in postmenopausal women. PMID- 2315888 TI - Normal and fibrinaemic patient plasma contain high-molecular weight crosslinked fibrin(ogen) derivatives with intact fibrinopeptide A. AB - Freshly drawn plasma samples from healthy subjects and from fibrinaemic patients were subjected to electrophoresis on SDS-agarose (unreduced material) or on SDS PAG (1D and 2D, reduced material) and Westernblotted. The blots were immunovisualized using either polyclonal anti-fibrinogen or a monoclonal antibody (Y18) to fibrinopeptide A-containing molecules. The following results were obtained: 1. Normal plasma as well as plasma from patients with fibrinaemia contained FXIII-crosslinked HMW oligomers, stabilized through gamma gamma dimerization as well as alpha-polymer formation and these oligomers contained molecules with intact A alpha-chain N-termini. 2. Cross-linked material amounted to less than 0.1% of the fibrinogen pool regardless of the sample studied, and apparently less in fibrinaemic patient plasma than in normal plasma. Thus, since the ratio of crosslinked fibrin(ogen) derivatives to that of fibrinogen was lower for fibrinaemic plasma than for normal plasma, it is suggested that the type of soluble fibrin which gives rise to a positive EGT in fibrinaemia patients is not crosslinked. PMID- 2315889 TI - Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease. AB - We have studied the activation state of the fibrinolytic system in 39 patients with systemic meningococcal disease (SMD). Patients defined as having fulminant septicemia (n = 13) with high (greater than 700 ng/L) levels of endotoxin (LPS) in plasma and severe coagulopathy, had significantly lower functional levels of plasminogen (P less than 0.05) and alpha-2-antiplasmin (P less than 0.01) and higher antigen levels of plasminogen activator inhibitor 1 (PAI-1) (P less than 0.01), and fibrin degradation products (FDP) (P less than 0.01), but not of PAI-2 (P greater than 0.1) as compared with less severely ill patients (meningitis and meningococcemia) (n = 25). A positive correlation existed between the admission (maximum) levels of LPS and PAI-1 (r = 0.86, P less than 0.0001). Decreasing admission levels of platelets were associated with increasing levels of PAI-1 (r = -0.55, P less than 0.001). After initiation of treatment with antibiotics and fresh frozen plasma, the PAI-1 levels declined rapidly. PAI-1 levels greater than 360 micrograms/L on admission predicted the development of a severe septic shock combined with renal impairment correctly in 12 of 13 patients (92%). None of 25 patients without multiple organ failure had PAI-1 levels greater than 260 micrograms/L. PAI-1 levels greater than 1850 micrograms/L were associated with 100% fatality. The results suggest that in the early phase of fulminant meningococcal septicemia an extensive plasmin generation occurs. On admission, however, high levels of PAI-1 seem to inhibit the plasmin generation, and thereby promote DIC. PMID- 2315890 TI - Further observations on in-vitro aggregation of rat platelets with different collagens. PMID- 2315891 TI - Influence of chemical modification of tryptophan residues on the properties of human antithrombin III. AB - According to the reaction conditions selected, chemical modification of tryptophan residues in antithrombin III by dimethyl (2-hydroxy-5 nitrobenzyl) sulfonium bromide (HNBSB) generated products with similar levels of modification (equivalent to 0.9 mole 2-hydroxy-5-nitrobenzyl (HNB) incorporated/mole of antithrombin III) but with high or low affinity for heparin. These products were subjected to digestion by cyanogen bromide and shown to be modified equivalently in fragment II containing Trp 189 and Trp 225 and fragment III containing Trp 49. The molar level of incorporation of HNB into these fragments was similar in the high and low affinity forms. Both high and low affinity forms showed loss of heparin cofactor activity. A recovery of heparin cofactor activity towards coagulation factor Xa was observed upon prolonged storage of low affinity forms at -70 degrees C. It is considered that the loss of high affinity for heparin upon modification of antithrombin III arises from change or stabilization of conformation associated with tryptophan modification and is not a singular property of modification of Trp 49. PMID- 2315892 TI - Platelet membrane defects in fawn hooded bleeder rats. AB - An inbred strain of fawn hooded rats with a congenital platelet defect shows a marked bleeding tendency with prolonged bleeding time. This haemorrhagic disorder has been exclusively related to a deficiency of nucleotides in platelet dense granules. When tested in cell electrophoresis platelets from fawn hooded bleeder rats showed a significantly lower electrophoretic mobility than normal rat platelets. Subsequent studies on the platelet membrane protein pattern by high resolution two-dimensional gel electrophoresis revealed the deficiency of a membrane glycoprotein (apparent molecular mass 90.000, isoelectric point 5.6), which is detectable in normal rat platelets after surface labeling by periodate tritiated sodium borohydride. It seems likely, that this glycoprotein defect contributes at least partially to the disorder of platelet function in fawn hooded bleeder rats. PMID- 2315894 TI - The effect of sulfation on the anticoagulant and antithrombin III-binding properties of a heparin fraction with low affinity for antithrombin III. AB - Heparin with low affinity for antithrombin III (ATIII) and devoid of anticoagulant activity was chemically oversulfated and fractionated by affinity for ATIII. The oversulfated material showed ATIII binding properties, as monitored by intrinsic fluorescence enhancement of ATIII. The fluorescence increase was comparable to that of the AT III high affinity fraction of native heparin. The estimated dissociation constants however, showed a 10-fold weaker binding of the oversulfated material to ATIII, Kd = 6.4 x 10(-8) M, as compared to native heparin, Kd = 0.63 x 10(-8) M. Concomitant with the binding-induced allosteric change in ATIII, the oversulfated material stimulated the ATIII thrombin and ATIII-factor Xa reactions. The high affinity fractions of native heparin and the sulfated material were almost equally effective in enhancing the rate of thrombin neutralization by ATIII. However, a 3-fold faster rate of factor Xa inactivation was found with the native high affinity material. PMID- 2315893 TI - Relationship between vessel wall 13-HODE synthesis and vessel wall thrombogenicity following injury: influence of salicylate and dipyridamole treatment. AB - We performed studies to determine the relationship between injured vessel wall thrombogenicity, vessel wall 13-hydroxyoctadecadienoic acid (13-HODE) synthesis and cAMP levels in rabbit treated with salicylate or dipyridamole. Injured vessel wall thrombogenicity was measured as the number of 3H-adenine labelled platelets adhered to the subendothelial basement membrane exposed by air injury in carotid arteries of rabbits treated orally with salicylate or dipyridamole. Vessel wall 13-HODE was measured by HPLC and vessel wall cAMP was measured by RIA. Vessel wall thrombogenicity was increased two-fold in rabbits treated with salicylate and decreased by half in rabbits treated with dipyridamole. The levels of vessel wall cAMP levels were correlated both with the plasma dipyridamole levels and increases in 13-HODE synthesis. cAMP levels were unaffected by salicylate treatment, but 13-HODE synthesis was decreased. We conclude that there is a significant relationship between vessel wall cAMP levels and 13-HODE synthesis, which in turn, influences subsequent vessel wall thrombogenicity. PMID- 2315895 TI - Platelet serotonergic mechanisms in ischaemic heart disease. AB - The uptake, basal content and efflux of serotonin (5-HT) from the platelets of patients of ischaemic heart disease (I.H.D.) was studied and compared with normal platelets. A significant increase in uptake and basal content of 5-HT as well as increase in 5-HT efflux was observed as compared to control. Our data indicate that I.H.D. is associated with platelet serotonergic dysfunction which seems to indicate that the platelets are preactivated in I.H.D. PMID- 2315896 TI - Influences of strenuous exercise (triathlon) on blood coagulation and fibrinolytic system. PMID- 2315898 TI - Fibrinolysis. Proceedings of the Second Osaka Symposium. Osaka, Japan, August 27, 1989. PMID- 2315897 TI - Urinary tissue factor activity in malignancy. PMID- 2315899 TI - Measurement of plasminogen activator inhibitor 1 (PAI-1) in plasma with various monoclonal antibody-based enzyme-linked immunosorbent assays. AB - Four monoclonal antibodies, MA-7D4, MA-7F5, MA-12A4 and MA-15H12, were raised against human plasminogen activator inhibitor-1 (PAI-1). MA-7D4 and MA-7F5 had an inhibitory effect on PAI-1 activity, whereas MA-15H12 and MA-12A4 did not affect PAI-1 activity. MA-7D4 was used previously as capture antibody in combination with MA-7F5 conjugated to horseradish peroxidase (7F5-HRP) to construct an ELISA which was 12 times more sensitive towards free PAI-1 as compared to PAI-1 in complex with human tissue-type plasminogen activator (t-PA) (Blood 71: 220-225, 1988). MA-15H12, as capture antibody, in combination with MA-12A4 corjugated to horseradish peroxidase (12A4-HRP) yielded an ELISA which was equally sensitive towards free PAI-1 and PAI-1/t-PA complex. Another ELISA was constructed using MA 15H12 as capture antibody in combination with an anti-t-PA antibody (MA-62E8) conjugated to horseradish peroxidase (62E8-HRP), allowing the specific measurement of t-PA/PAI-1 complexes and the development of an immunofunctional method for the specific quantitation of active PAI-1. These assays were then used to measure PAI-1 levels in plasma and the values obtained were compared with the data obtained by functional methods. It was found that 44% to 60% of free PAI-1 antigen in normal plasma is active and that t-PA occurs mainly as t-PA/PAI-1 complexes. In plasma from 48 patients suffering from angina pectoris no statistical difference in PAI-1 activity, PAI-1 antigen or PAI-1/t-PA complex could be observed as compared to normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2315900 TI - [Lens extraction]. PMID- 2315901 TI - [Worldwide interest for research on the strange relationship between man and animal]. PMID- 2315902 TI - [The Veterinary Chief Inspection for Public Health. Plan of campaign against parrot fever]. PMID- 2315903 TI - 19th annual meeting of the German Society for Thoracic and Cardiovascular Surgery. February 22, 1990, to February 24, 1990, Bad Nauheim. Abstracts. PMID- 2315904 TI - [The dyspneic infant. Interpretation of symptoms of lower airway disorders in the first year of life]. AB - A number of age-related anatomical and physiological factors place the respiratory system of the neonate and young infant in a potentially vulnerable position during disease states. Maintenance of a lung volume necessary for effective gas exchange is compromised by the floppy chest wall, the relatively stiff lungs and the horizontal position of the body. Respiratory muscles are prone to fatigue in case of increased respiratory loads and fail to move the rib cage efficiently. Many signs of lower airway disease, observed during the physical examination of the young infant, can be related to these factors. Awareness of them helps in the interpretation of these symptoms in order to make the correct diagnosis and to initiate treatment. PMID- 2315905 TI - [Lung infections with atypical features]. AB - The clinical difference between a lobar pneumonia caused by pneumococci or other bacterial agents and lower respiratory tract infections presenting with atypical symptoms is important. Mycoplasma pneumoniae, chlamydia species, Coxiella burnetii and several viruses amongst others are micro-organisms which cause atypical symptoms. All the time new types of micro-organisms like Ureaplasma urealyticum are found as a cause of pneumonia with atypical symptoms. Special diagnostic tools like cultures, serological or antigen detection are often needed to determine the exact causative agent. Clinical data are important to suspect a specific micro-organism. PMID- 2315907 TI - The hospital-physician relationship. PMID- 2315906 TI - [Early diagnosis of cystic fibrosis: to screen or not to screen?]. AB - After an experimental neonatal screening program for cystic fibrosis (CF) had been carried out in the Netherlands during 1973-1979, a follow-up study to evaluate the effects of neonatal screening was started in 1980. The results of this study suggest that early diagnosis and appropriate treatment may prevent serious deterioration and death at a young age, and may reduce the extent of early irreversible lung damage in patients with CF. The short period between the birth of an affected child and the diagnosis and the timely information on the high recurrence risk, may lead to a significant reduction in subsequent births in the case of neonatal screening. However it is still doubtful whether general neonatal screening for CF should be recommended, as treatment directed against the harmful effects of the genetic defect is not yet available. PMID- 2315908 TI - Physician-nurse relationships. PMID- 2315909 TI - Understanding utilization data and detecting provider "gaming". PMID- 2315910 TI - Physician recruitment and credentialing. PMID- 2315911 TI - The evolution of faculty practice plans. PMID- 2315912 TI - Pharmacokinetics of benzene. AB - A physiologically based pharmacokinetic model was developed and used to describe the pharmacokinetics of benzene in three species: mice, rats, and humans. For each species, the body was divided into five anatomical compartments, consisting of liver, fat, bone marrow, and muscle, and organs such as brain, heart, kidney, and viscera, connected by the arterial and venous blood flow pathways. Metabolism of benzene followed Michaelis-Menten (nonlinear) kinetics in all species and occurred primarily in the liver compartment and, to a lesser extent, in the bone marrow. Comparison of model results with empirical data on inhalation, gavage, and intraperitoneal and subcutaneous injection in mice, rats, and humans, demonstrates the utility of a physiological pharmacokinetic model in describing the pharmacokinetics of benzene in three species across multiple routes of exposure. PMID- 2315914 TI - Effects of two pyrethroids, bioallethrin and deltamethrin, on subpopulations of muscarinic and nicotinic receptors in the neonatal mouse brain. AB - Ten-day-old NMRI mice were given deltamethrin, bioallethrin, or the vehicle once daily for 7 days. The doses used were as follows: deltamethrin, 0.71 and 1.2 mg/kg body wt; bioallethrin, 0.72 and 72 mg/kg body wt; and 20% fat emulsion vehicle, 10 ml/kg body wt. The mice were killed 24 hr after the last administration, and crude synaptosomal fractions (P2) were prepared from the cerebral cortex and hippocampus. The densities of the muscarinic and nicotinic receptors were assayed by measuring the amounts of quinuclidinyl benzilate ([3H]QNB) and [3H]nicotine, respectively, specifically bound in the P2 fraction. The proportions of high- and low-affinity binding sites of the muscarinic receptors were assayed in a displacement study using [3H]QNB/carbachol. The two types of pyrethroids affected the cholinergic system in the neonatal mouse brain in two different ways. At the lower dose, which did not cause any neurotoxic symptoms, both pyrethroid types affected the muscarinic receptors in the cerebral cortex. Here deltamethrin caused an increase and decrease in the percentage of high- and low-affinity binding sites, respectively, whereas the reverse was observed after bioallethrin treatment. Deltamethrin treatment also caused an increase in the density of nicotinic receptors in the cerebral cortex. The higher doses revealed typical symptoms of pyrethroid poisoning, such as choreoathetosis and tremor for deltamethrin and bioallethrin, respectively. The symptoms declined gradually during each successive day of administration and had disappeared by Day 4. At this dose deltamethrin affected the muscarinic receptors in the hippocampus and the nicotinic receptors in the cerebral cortex, whereas bioallethrin had no apparent effect. This study further supports that the cholinergic system under rapid development in the neonatal mouse is sensitive to xenobiotics. PMID- 2315913 TI - Evaluation of a two-drug combination pretreatment against organophosphorus exposure. AB - A pretreatment combination of physostigmine and azaprophen (6-methyl-6 azabicyclo[3.2.1]octan-3-ol-2,2-diphenylpropionate), a novel cholinolytic, was evaluated for its ability to minimize soman-induced incapacitation and lethality in guinea pigs. This was accomplished by using response surface methodology to model and analyze the combination, varying physostigmine from 0 to 194 micrograms/kg, azaprophen from 0 to 5 mg/kg, and soman from 30 to 150 micrograms/kg. One hundred percent survival was achieved against 5 LD50 of soman using as little as 100 micrograms/kg of physostigmine in the presence of 5 mg/kg azaprophen. Both survival and soman-induced incapacitation were similarly affected by this pretreatment combination. For both endpoints, greater efficacy was achieved with the combination than could be achieved with either component alone (therapeutic synergism). This suggests that such a pretreatment combination may prove very efficacious against soman-induced lethality and incapacitation in higher species. PMID- 2315915 TI - Acute cadmium uptake by rabbit kidneys: mechanism and effects. AB - Trapping of an arterial bolus in the kidney by 40 sec aortic occlusion permitted demonstration of diffusion-limited and Zn-sensitive renal uptake of nonfiltered but diffusible Cd from plasma; mercaptoethanol (ME) or 2,3-dimercaptopropanol (BAL) had been added to the bolus to prevent sequestration of the metals by plasma protein. Cadmium taken up by the kidney under these conditions, whether from blood or glomerular filtrate, unlike Zn, did not return to blood over a period of 2-3 min. Nor was Cd thus accumulated removed by EDTA; it had presumably been transferred into cells. The diffusion dependence of this internalization shows it to be a relatively slow process, as it is in jejunum. In contrast, uptake of Cd tightly bound in a lipid-soluble complex with diethyldithiocarbamate (DDTC) is rapid and flow dependent. Slow uptake in the presence of ME and its inhibition by Zn are therefore not likely to involve movement of undissociated ME complex across the cell membranes. Instead, it is suggested that (1) Cd-binding sites on the membrane possess a relatively high affinity for Cd and can compete for it with ME, and (2) it is the resulting Cd-membrane interaction which, as in jejunum, is depressed by Zn. During transient occlusion kidneys could be loaded with up to 25 micrograms Cd/g cortex without evidence of immediate malfunction. Inhibition of amino acid transport, as previously described, is seen only after an initiation period of 1-2 days following CdME injection, although cortical Cd levels at that time have decreased. The finding of a slowly developing inhibition of amino acid carrier systems suggests an indirect action of Cd; by implication, unique threshold concentrations should not be defined for Cd in renal cortex following subchronic exposures without reference to the duration of exposure. PMID- 2315916 TI - Triadimefon, a triazole fungicide, induces stereotyped behavior and alters monoamine metabolism in rats. AB - Triadimefon, a triazole fungicide, has been observed to increase locomotion and induce stereotyped behavior in rodents. The present experiments designed to characterize the stereotyped behavior induced by triadimefon used a computer supported observational method, and tested the hypothesis that these observed effects involved central dopaminergic systems. Adult male and female Sprague Dawley rats were injected with triadimefon (0, 50, 100, and 200 mg/kg) in corn oil (2 ml/kg ip) 4 hr prior to behavioral assessment. The two lowest doses of triadimefon increased the frequency of locomotion and rearing, while the highest dose induced highly stereotyped behaviors, including backward locomotion, circling, and head weaving. Immediately after behavioral testing, the rats were sacrificed, and the striata and olfactory tubercles, terminal fields of the nigrostriatal and mesolimbic dopamine systems, respectively, were removed. Steady state concentrations of the monoamines dopamine and serotonin and their metabolites were determined by HPLC-EC. In independent experiments, the direct effects of triadimefon on dopamine (D1 and D2) receptor binding and dopamine sensitive adenylate cyclase activity were assessed in vitro using rat striata. Dopamine concentrations were increased in olfactory tubercles, but decreased in striatum. Concentrations of 5-hydroxyindoleacetic acid (the major metabolite of serotonin) were increased only in striatum, and only in animals treated with 200 mg/kg triadimefon. In vitro, triadimefon neither competed with D1 or D2 dopaminergic radioligands nor affected dopamine-stimulated adenylate cyclase activity. Together these behavioral and biochemical data lend support to the hypothesis that triadimefon may have actions similar to those produced by indirect-acting dopamine agonists. PMID- 2315918 TI - Physiologically based pharmacokinetic modeling of the lactating rat and nursing pup: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid. AB - A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the lactating rat and nursing pup. The lactating dam was exposed to TCE either by inhalation or by ingestion in drinking water. The nursing pup's exposure to TCE was by ingestion of maternal milk containing TCE. The kinetics of trichloroacetic acid (TCA), a metabolite of TCE, were described in the lactating dam and developing pup by a hybrid one compartment model. The lactating dam's exposure to TCA was from metabolism of TCE to TCA. The pup's exposure to TCA was from metabolism of TCE ingested in suckled milk and from direct ingestion of TCA in maternal milk. For the PB-PK model, partition coefficients (PCs) were determined by vial equilibration, and metabolic constants for TCE oxidation, by gas uptake methods. The blood/air and the fat/blood PCs for the dam were 13.1 and 34.2, and for the pup, 10.6 and 42.3, respectively. The milk/blood PC for the dam was 7.1. In lactating rats and rat pups (19-21 days old) the maximum velocities of oxidative metabolism were 9.26 +/ 0.073 and 12.94 +/- 0.107 mg/kg/hr. The plasma elimination rate constant (K = 0.063 +/- 0.004 hr-1) and apparent volume of distribution (Vd = 0.568 liter/kg) for TCA in the lactating dam were estimated from both intravenous dosing studies and an inhalation study with TCE. For the pup, K (0.014 +/- hr-1) and Vd (0.511 liter/kg) were estimated from a single 4-hr inhalation exposure with TCE. The dose-rate-dependent stoichiometric yield of TCA from oxidative metabolism of TCE in the lactating rat is 0.17 for a low-concentration inhalation exposure (27 ppm TCE) and 0.27 for an exposure above metabolic saturation (about 600 ppm TCE). For the pup, the stoichiometric yield of TCA is 0.12. With changing physiological values during lactation for compartmental volumes, blood flows, and milk yields obtained from the published literature and kinetic parameters and PCs determined by experimentation, a PB-PK model was constructed to predict maternal and pup concentrations of TCE and TCA. To test the fidelity of the PB-PK lactation model, a multiday inhalation exposure study was conducted from Days 3 to 14 of lactation and a drinking water study, from Days 3 to 21 of lactation. The inhalation exposure was 4 hr/day, 5 days/week, at 610 ppm. The TCE concentration in the drinking water was 333 micrograms/ml. Prediction compared favorably with limited data obtained at restricted time points during the period of lactation. PMID- 2315917 TI - Metabolism of the liver tumor promoter ethinyl estradiol by primary cultures of rat hepatocytes. AB - Previously, we reported that relatively high micromolar concentrations of the liver tumor promoter 17 alpha-ethinyl estradiol (EE2) stimulated DNA synthesis and enhanced the DNA synthetic response to epidermal growth factor (EGF) in primary cultures of female rat hepatocytes [J.D. Yager, B.D Roebuck, T.L. Paluszcyk, and V.A. Memoli, Carcinogenesis 7, 2007-2014 (1986); Y.E. Shi and J.D. Yager, Cancer Res. 49, 3574-3580 (1989)]. In this study, our goal was to examine the metabolism of EE2 in cultured hepatocytes. After 4, 24, and 48 hr of culture, hepatocytes maintained their ability to convert up to 95% of a 4 nM concentration of [3H]EE2 to polar conjugates within 4 hr. EE2 at 2 microM was also 95% metabolized within 4 hr. HPLC analysis of the metabolites confirmed the rapid disappearance of [3H]EE2 and the formation of polar conjugates as detected by organic extraction. HPLC separation of hydrolyzed conjugates indicated that the major aglycone was the parent compound, EE2. In general, the metabolites differed both qualitatively and quantitatively from those reported in vivo in the rat. The rapid metabolism of EE2 by hepatocytes in culture may, at least in part, explain the high concentrations of EE2 required to stimulate DNA synthesis in cultured hepatocytes and to potentiate the response to EGF. PMID- 2315919 TI - Tobacco smoke suppresses T cells but not antigen-presenting cells in the lung associated lymph nodes. AB - Chronic inhalation of cigarette smoke in mice preferentially inhibited the antigen-specific T-cell proliferative response of lung-associated lymph nodes compared to anatomically distant lymph nodes. Cell mixing experiments demonstrated that the defect in smoked mice resulted from an abnormality in T lymphocyte function. In contrast, the activity of antigen-presenting cells was similar in smoked and sham-smoked control animals. These results suggest that T cell function in lung-associated lymphoid tissue may be inhibited in smokers, leading to a localized predisposition to respiratory tract infections. PMID- 2315920 TI - Effect of oral cadmium exposure during pregnancy on maternal and fetal zinc metabolism in the rat. AB - To study the effect of cadmium exposure on maternal and fetal zinc metabolism, rats were exposed to 0, 5, 50, or 100 ppm Cd in the drinking water on Days 6 through 20 of pregnancy. In comparison to controls, fetal and maternal weights were slightly reduced in the 50- and 100-ppm groups, but not the 5-ppm group. Multiple regression analysis revealed that in the 50-ppm group, but not in the 100-ppm group, the decrease in fetal weight was not solely a consequence of decreased maternal weight. Cd accumulated in a dose-dependent manner in both maternal organs and fetuses, although the absolute concentrations in fetuses were very low as compared to those of maternal tissues. In the 50- and 100-ppm groups, zinc concentrations were significantly increased in maternal liver and kidney, and significantly decreased in fetal liver. The changes in tissue Zn concentrations were accompanied by altered Zn-metalloenzyme activities in both maternal and fetal tissues. These findings support the hypothesis that Cd-induced maternal zinc retention is responsible for fetal Zn deprivation and impaired fetal growth. PMID- 2315921 TI - Three forms of trichloroethylene-metabolizing enzymes in rat liver induced by ethanol, phenobarbital, and 3-methylcholanthrene. AB - In vitro metabolism of trichloroethylene (TRI) and trichloroethanol (TCE) was investigated using liver microsomes from control and ethanol-, phenobarbital (PB) , and 3-methylcholanthrene (MC)-treated rats. At least three forms of enzymes were involved in TRI metabolism. One was a low-Km type normally existing in microsomes from control rats. The ethanol-inducible enzyme was found to be catalytically identical to this low-Km isozyme. Another was a high-Km type which was induced exclusively by PB, and a third was an MC-inducible isozyme with a Km value between those of ethanol- and PB-inducible isozymes. Although MC treatment did not affect the rate of TRI metabolism in vitro, both ethanol and PB treatment markedly enhanced the metabolism. Ethanol-induced enhancement was different from PB-induced enhancement in that ethanol enhanced the metabolism predominantly at low substrate concentrations, whereas PB did so at high concentrations. In addition, TRI metabolism with enzymes from ethanol-treated rats was inhibited by the substrate itself at high concentrations. MC treatment of rats had little or no influence on the rate of TCE metabolism in vitro, whereas both ethanol and PB enhanced the microsomal conversion of TCE to chloral hydrate. As in the case of TRI metabolism, ethanol induced a microsomal TCE-metabolizing enzyme of low Km, whereas PB preferentially induced an enzyme of high Km. PMID- 2315922 TI - L-methionine antagonism of cis-platinum nephrotoxicity. AB - L-Methionine administered simultaneously with cis-platinum (CDDP) iv results in a significant reduction of the nephrotoxicity normally associated with CDDP without any apparent effect on the antineoplastic activity for rats bearing the Walker 256 carcinosarcoma. CDDP given with L-methionine at a 1:20 mole ratio can be administered to rats at doses up to 35 mg/kg iv with the survival of all treated animals (3/3) and up to 56 mg/kg iv (bolus injection) with the survival of 3/6 animals, while CDDP administered alone at these levels is lethal. A reduced level of protection against the nephrotoxicity was also achieved at lower mole ratios of L-methionine to CDDP. Renal function was monitored using BUN and serum creatinine levels, and gastrointestinal toxicity by weight changes during the course of the experiments. A histopathological examination of the kidneys was also performed to evaluate the protection provided by L-methionine. Under the conditions used, the reaction between L-methionine and CDDP does not appear to proceed so rapidly as to interfere with the antitumor activity of the CDDP. The examination of structural analogs as agents for the control of CDDP-induced nephrotoxicity revealed that the C-S-C-group is the essential group for the protective action in these structures. Although L-methionine can provide renal protection in rats given high doses of CDDP, it does not prevent the accumulation of platinum in the kidney. PMID- 2315923 TI - Metabolism of the arylamide herbicide propanil. II. Effects of propanil and its derivatives on hepatic microsomal drug-metabolizing enzymes in the rat. AB - Propanil (3,4-dichloropropionanilide) is an arylamide herbicide that has been reported to be contaminated with the cytochrome P450 enzyme inducers 3,3',4,4' tetrachloroazobenzene (TCAB) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB), which are structural analogs of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We determined if treatment of rats with TCAB, TCAOB, propanil, 3,4-dichloroaniline, TCDD, or phenobarbital induced the hepatic microsomal metabolism of propanil and 3,4-dichloroaniline. Acylamidase-catalyzed hydrolysis of propanil to 3,4 dichloroaniline was not induced by any of the pretreatments; however, hydroxylation of propanil at the 2'-position was induced by TCDD, TCAB, TCAOB, propanil, and 3,4-dichloroaniline pretreatments. Ring- and N-hydroxylations of 3,4-dichloroaniline were induced by TCDD, TCAB, TCAOB, and 3,4-dichloroaniline pretreatments. Microsomal 7-ethoxyresorufin-O-deethylase (EROD) and 7 benzoxyresorufin-O-dealkylase (BROD) activities and electrophoretic mobility of microsomal proteins suggested that cytochromes P450c and P450d were induced by TCAB and TCAOB pretreatment. EROD, BROD, and 7-pentoxyresorufin-O-dealkylase activities were slightly increased in microsomes from propanil- and 3,4 dichloroaniline-pretreated rats, which suggests that these compounds may be weak inducers of cytochrome P450 isozymes. PMID- 2315924 TI - Toxicity of cadmium to rat osteosarcoma cells (ROS 17/2.8): protective effect of 1 alpha,25-dihydroxyvitamin D3. AB - Inadequate vitamin D intake is an important cofactor in clinical and experimental bone disease induced by chronic cadmium exposure. The interaction was investigated by culture of rat osteoblastic osteosarcoma cells (ROS 17/2.8) in a serum-free medium with equimolar concentrations of cadmium chloride and 1 alpha,25-(OH)2 vitamin D3. After addition of cadmium alone to culture medium, the unstimulated secretion of osteocalcin and cellular alkaline phosphatase activity were inhibited at 10 pM, and of DNA synthesis and proline incorporation into collagen at 500 nM. In the presence of equimolar amounts of cadmium and 1 alpha,25-(OH)2 vitamin D3, all four responses paralleled those of 1 alpha,25 (OH)2 vitamin D3 alone up to the inhibitory concentration of 500 nM cadmium. Neither 10 nM 1 alpha,25-(OH)2 vitamin D3 nor 1 microM cadmium induced synthesis of metallothionein in these cells indicating that the protective effect of D3 was not related to the induction of a metallothionein-like protein in ROS 17/2.8 cells. In the presence or absence of D3, cadmium inhibited osteoblastic function at concentrations below the whole-organ concentration of cadmium in bone as reported in experimental and clinical cadmium-induced osteotoxicity. The extreme sensitivity of ROS 17/2.8 cells to cadmium may relate to the absence of metallothionein synthesis. PMID- 2315925 TI - Proliferative responses of rat nasal epithelia to ozone. AB - The epithelium of the female Fischer 344/N rat anterior nasal cavity was examined and found to be composed of four types of epithelia: squamous, ciliated respiratory, nonciliated cuboidal/transitional, and olfactory. DNA replication in these tissues was monitored by bromodeoxyuridine (BrdUrd) incorporation. Labeled cells were identified using a monoclonal antibody recognizing BrdUrd. Ciliated respiratory, nonciliated cuboidal/transitional, and olfactory epithelia from control animals had a low level of DNA replication (1 labeled cell/mm basal lamina); in contrast, the squamous epithelium contained 40 labeled cells per millimeter basal lamina. Female Fischer 344/N rats were exposed to 0.0, 0.12, 0.27, or 0.8 ppm ozone, 6 hr/day for up to 7 days. Observations were made after 3 or 7 days of exposure and after 3 or 7 days of recovery from the 7-day exposure. Following exposure to 0.8 ppm ozone, a transient but marked increase in DNA replication was seen in the nonciliated cuboidal/transitional, while in ciliated respiratory and olfactory epithelia the transient increase in DNA replication was less marked. This increase was prominent after 3 days of exposure and absent by 7 days of exposure in all but the cuboidal/transitional epithelium. Exposure to 0.8 ppm ozone for either 3 or 7 days resulted in hyperplasia of the cuboidal epithelium. A depressed level of DNA replication was seen in the squamous epithelium following 7 days of recovery from 7 days of ozone exposure to 0.8 ppm ozone. This study shows that there are regional differences in DNA replication within the anterior nasal epithelium of the rat and that these levels are modulated by exposure to irritants. The cuboidal/transitional epithelium was the most responsive epithelial cell type to the effects of ozone exposure and may, therefore, provide a sensitive indicator of irritant damage to the respiratory tract. PMID- 2315926 TI - Amiodarone-mediated increase in intracellular free Ca2+ associated with cellular injury to human pulmonary artery endothelial cells. AB - The cardiac antidysrrhythmic drug amiodarone can give rise to potentially fatal pulmonary toxicity in large numbers of patients. The effect of amiodarone on Ca2+ homeostasis and cell injury has been studied using human pulmonary artery endothelial (HPAE) cells in vitro. Amiodarone produced a concentration-dependent increase in intracellular free Ca2+ concentration ( [Ca2+]i) to micromolar levels that are similar to those seen with physiological stimuli that increase [Ca2+]i. Unlike physiological stimuli, the rise in [Ca2+]i produced by amiodarone developed slowly and was maintained over at least 30 min. Omitting Ca2+ from the external medium reversibly prevented the amiodarone-induced rise in [Ca2+]i. Amiodarone treatment increased the apparent first order rate constants for 45Ca2+ influx and efflux in intact HPAE cells. 45Ca2+ accumulation into the endoplasmic reticulum of saponin-permeabilized HPAE cells was decreased by amiodarone treatment. The release of 45Ca2+ from the endoplasmic reticulum stores by the putative intracellular second messengers inositol-1,4,5-trisphosphate, arachidonic acid, and Ca2+ was blocked by amiodarone treatment. The changes in Ca2+ homeostasis coincide with an increase in [3H]deoxyglucose release as a measure of early cell injury by amiodarone. It is concluded that amiodarone can produce an increase in [Ca2+]i by an action on the plasma membrane that allows the influx of external Ca2+. This increase in [Ca2+]i, together with other changes in Ca2+ homeostasis, may be responsible for the early cell injury associated with amiodarone toxicity. PMID- 2315927 TI - Phenobarbital pretreatment alters the localization of CCl4-induced changes in rat liver microsomal fatty acids. AB - Phenobarbital treatment induces an isozyme(s) of liver microsomal cytochrome P450 susceptible to CCl4 and enhances the latter's lethality. We have now studied phenobarbital's effect on the specificity of phosphatidyl fatty acid changes in rat liver microsomes. Male Sprague-Dawley rats were pretreated with three daily ip doses of phenobarbital (50 mg/kg) or saline and then orally dosed with CCl4 (2.5 ml/kg). Liver microsomes were prepared 7.5 to 180 min after CCl4 treatment, the lipid fraction was extracted, diene conjugate content was determined, and phospholipids were separated by HPLC for fatty acid content determination. Protein, phospholipid, and phosphatidyl fatty acid residue loss occurred early (7.5 to 30 min) and in some cases later (60 to 180 min) in both pretreated groups, suggesting that two phases of CCl4-mediated injury occurred. Phenobarbital pretreatment accelerated the CCl4-induced formation of diene conjugates in the microsomal lipids. In studies on the separated phospholipids, phenobarbital alone altered microsomal fatty acid content, primarily decreasing arachidonic acid in favor of linoleate, particularly in phosphatidylserine. During the early phase of CCl4 injury, phenobarbital pretreatment shifted the major loss of arachidonic acid from phosphatidylserine to phosphatidylethanolamine. During the later phase, arachidonic acid loss was still prominent, but the most extensive CCl4-induced changes in fatty acids occurred in the neutral lipid fraction, regardless of pretreatment. These changes included loss of neutral lipid linoleic and docosahexanoic acids associated with an increase in palmitic acid. These data demonstrate that phenobarbital pretreatment is associated with a shift in the predominant phospholipid locus from phosphatidylserine to phosphatidylethanolamine for the early CCl4-induced fatty acid changes in rat liver microsomes. PMID- 2315928 TI - Cytochrome P450 isozyme induction by methyl ethyl ketone and m-xylene in rat liver. AB - The rat hepatic cytochrome P450 induction pattern caused by administration of a high peroral dose of methyl ethyl ketone (MEK, 1.4 ml/kg once daily for 3 consecutive days) and m-xylene (1.0 ml/kg X 3) was studied by catalytic activity and immunoblotting techniques. MEK caused a marked increase in the amount of P450 isozymes belonging to the phenobarbital- and ethanol-inducible P450 subfamilies P450IIB and P450IIE, respectively. Catalytic activities linked with these isozymes, pentoxyresorufin O-depentylase (P450IIB), aniline hydroxylase, and N nitrosodimethylamine N-demethylase (P450IIE), were also increased (18.0-, 5.4-, and 2.4-fold, respectively). The activity of ethoxyresorufin O-deethylase, which is predominantly linked with the polycyclic aromatic hydrocarbon-inducible P450 isozymes, was also increased 2.3-fold without an apparent increase in the amount of the respective P450 protein (P450IA). m-Xylene caused a similar induction pattern with less effect on P450IIE. Simultaneous administration of MEK and m xylene resulted in an additive or, in the case of pentoxyresorufin O-depentylase, a potentiating effect on P450-linked catalytic activities. These data indicate that MEK and m-xylene elicit a qualitatively similar induction of P450 isozymes, which may play a role in the metabolic interactions of these compounds. PMID- 2315929 TI - Cadmium-metallothionein-induced kidney dysfunction increases magnesium excretion in the rat. AB - Urinary excretion of the major minerals, calcium (Ca), magnesium (Mg), sodium (Na), and potassium (K), as well as of protein and metallothionein, was studied following the injection of cadmium-metallothionein (CdMT) in rats. Animals were given vehicle (saline) and 0.4 and 0.8 mg Cd/kg body wt as CdMT. A marked, relatively early, and reversible increase in Mg excretion was seen. The increase was dose-related, indicating a close connection to the typical Cd-derived cellular damage in the renal tubular epithelium, including an early reversible Ca excretion and a late reversible protein excretion. The increase in Mg excretion was similar in magnitude to the one for Ca and much more prominent than that recorded for Na and K. The appearance of Mg and Ca excretion peaks at an early stage after CdMT injection makes it likely that this effect is an early event in the process of development of cellular damage and does not merely represent unspecific cellular damage giving rise to proteinuria. PMID- 2315930 TI - Effects of fasting on cadmium toxicity, glutathione metabolism, and metallothionein synthesis in rats. AB - Acute oral toxicity of Cd (as cadmium chloride) was enhanced in rats fasted 24 hr, as shown by a markedly decreased LD50. To examine the relationship among Cd toxicity, hepatic glutathione (GSH), and metallothionein (MT) during fasting, rats were administered 75 mg Cd/kg orally 24 hr after fasting and euthanized after a further 4 or 24 hr for various assays. Serum glutamic-pyruvic transaminase activity 24 hr after Cd treatment was higher in fasted rats than in fed rats. Both total GSH and nonprotein sulfhydryl (NPSH) concentrations in liver decreased to 50% of control levels after 28 hr of fasting and returned to 75% of control values by 48 hr. Total hepatic GSH concentration in fed rats decreased 4 and 24 hr after Cd treatment, whereas that in fasted rats remained unchanged at 4 hr and decreased significantly at 24 hr. Cd uptake by the liver (both concentration and content) 24 hr after Cd treatment was higher in fasted rats than in fed rats. Hepatic MT concentration was markedly increased by Cd treatment and higher in fasted rats than in fed rats. There was no relationship between Cd toxicity and hepatic thiobarbituric acid (TBA) value, an indicator of lipid peroxidation. Fasting had no effect on hepatic GSH peroxidase and GSH reductase activities. These enzymes probably are not involved in Cd toxicity. On histological examination, focal degenerative and necrotic changes were observed from the midlobular to the pericentral region in the livers of fed rats 24 hr after Cd treatment. These changes were enhanced by fasting, diffusing from the pericentral to the periportal region. Histochemical examination revealed a heterogeneous distribution of GSH in the livers of fed rats, with strong staining of GSH in the periportal region. This heterogeneous distribution of GSH in liver was not observed in fed rats 4 hr after Cd treatment or in fasted rats at 24 hr. The present results suggest that hepatic GSH plays an important role in protection against Cd toxicity before the onset of MT synthesis. Animals in bad condition, such as that resulting from interruption of nutrient supply, cannot be protected against Cd toxicity even if the hepatic MT level is high. PMID- 2315931 TI - Organ-selective switching of 3-methylindole toxicity by glutathione depletion. AB - A high dose (550 mg/kg) of 3-methylindole (3MI) specifically damaged pulmonary tissue in Swiss-Webster mice without causing any hepatic or renal necrosis. When a glutathione depleter, L-buthionine-(S,R)-sulfoximine (BSO, 1.0 mmol/kg), was administered to mice 3 hr before a low dose of 3-methylindole (75 mg/kg), significant renal damage was observed by histopathological examination after 4 hr. The nephrotoxicity occurred without any observable pathological damage to lung tissues. Increased doses of BSO caused dose-dependent increases in renal toxicity. A low dose of BSO (1.0 mmol/kg) caused no depletion of renal glutathione levels, a large depletion of hepatic glutathione levels (60% of control values), and much larger increases in covalent binding of [methyl-14C]3 methylindole to renal tissues (3.4-fold) than to hepatic tissues (1.5-fold) or pulmonary tissues (2.1-fold). No evidence of hepatic or pulmonary histopathological damage was observed at any dose of BSO with 75 mg/kg 3MI. These results indicate that a shift in organ selectivity of 3MI-induced toxicity from pulmonary to renal sites occurs as a result of glutathione depletion in hepatic tissues. The production of a toxic metabolite in the livers of glutathione depleted mice that is circulated to susceptible renal cells may be the mechanism of this interesting organ-selective shift in toxicity of 3MI. PMID- 2315932 TI - Evaluation of estimations in vitro of tissue/blood distribution coefficients for organothiophosphate insecticides. AB - Physiologically based pharmacokinetic (PBPK) modeling of foreign chemicals is dependent on the accurate determination of their tissue/blood distribution coefficients, Kp (partition coefficients). The present study was undertaken to evaluate the validity of the in vitro estimation of the Kp values of the organothiophosphate insecticides parathion and methyl parathion by equilibrium dialysis. Data derived from previously published studies that utilized single pass perfusions of mouse livers in situ with parathion or methyl parathion were analyzed to determine liver/perfusate Kp values from the equation Kp = (t 1/2ss) (Q)/(0.693) (VH), where Kp is the liver/perfusate distribution ratio, t 1/2ss is the half-life for approach to steady state of the chemical, VH is the liver volume, and Q is the perfusate flow rate. Kp values for methyl parathion were calculated to be 16.4 +/- 7.5 and 9.5 +/- 2.7 (mean +/- SD) for perfused livers and equilibrium dialysis, respectively, while estimates of Kp for parathion were 15.6 +/- 6.3 and 19.5 +/- 5.5 for perfused livers and equilibrium dialysis, respectively. These results indicate that equilibrium dialysis can be utilized to give an accurate estimate of tissue partitioning of parathion and methyl parathion from perfusate into perfused mouse livers. PMID- 2315933 TI - A radioimmunoassay for perch (Perca fluviatilis) metallothionein. AB - A sensitive radioimmunoassay (RIA) for the measurement of metallothionein (MT) from perch (Perca fluviatilis) has been developed. The method is a double antibody RIA with rabbit anti-perch MT serum as first antibody, goat anti-rabbit immunoglobulin G as second antibody, and perch MT conjugated to 125I-labeled Bolton-Hunter reagent as tracer. The rabbit antiserum raised against perch MT recognizes rainbow trout (Oncorhynchus mykiss) MT, but shows little cross reactivity with horse MT. At a dilution of 1:2000, the MT antibodies bind 36% of the tracer when no cold ligand is present. The sensitivity of the assay is 15 pg perch MT per tube and the practical working range is 0.15-250 ng perch MT per tube. The RIA allows determination of MT in plasma or lysed blood cells at concentrations as low as 3.0 ng/ml and in tissues at levels above 9.0 ng/g (wet weight). Intra- and interassay coefficients of variation were 6 and 10%, respectively. PMID- 2315934 TI - Metabolism of the arylamide herbicide propanil. I. Microsomal metabolism and in vitro methemoglobinemia. AB - Methemoglobinemia produced by exposure to the herbicide propanil (3,4 dichloropropionanilide) is thought to be mediated by toxic metabolites formed during the hepatic clearance of the parent compound. We examined the metabolism of propanil and 3,4-dichloroaniline in rat liver microsomes to identify metabolites that may be involved in propanil-induced methemoglobinemia. The major pathway of propanil metabolism in microsomal incubations was acylamidase catalyzed hydrolysis to 3,4-dichloroaniline. The reaction did not require NADPH, and was inhibited by the acylamidase inhibitors paraoxon and sodium fluoride. Oxidized metabolites were isolated by high-performance liquid chromatography, and identified as 2'-hydroxypropanil and 6-hydroxypropanil by comparison of their mass and nuclear magnetic resonance spectra to those of synthetic standards. Major microsomal metabolites of 3,4-dichloroaniline were 6-hydroxy-3,4 dichloroaniline and N-hydroxy-3,4-dichloroaniline. Both N-hydroxy-3,4 dichloroaniline and 6-hydroxy-3,4-dichloroaniline directly oxidized hemoglobin in rat erythrocyte suspensions in a concentration-dependent manner; however, the potency of N-hydroxy-3,4-dichloroaniline was at least an order of magnitude greater than that of 6-hydroxy-3,4-dichloroaniline. PMID- 2315935 TI - Symposium on New and Developing Techniques in Respiratory Toxicology. October 1988. Proceedings. PMID- 2315936 TI - The role of intestinal microflora in the metabolic activation of 6-nitrochrysene to DNA-binding derivatives in mice. AB - 6-Nitrochrysene has previously been shown to be a potent lung and liver carcinogen following i.p. administration to newborn mice and to be metabolically activated to DNA-binding derivatives by nitro-reduction or a combination of nitro reduction and ring oxidation. In this study, we have examined fecal metabolites and DNA-carcinogen adducts in 5-week-old conventional and germfree Balb/c mice treated with [3H]6-nitrochrysene in order to determine if the metabolic activation pathway(s) for this compound in these mice differs from that observed in preweanling mice. We further evaluated the role of the intestinal microflora on the metabolism and generation of DNA-reactive metabolites in this system. The amount of 6-aminochrysene excreted in the feces of germfree mice within 48 h after treatment with a single i.p. dose of [3H]6-nitrochrysene (0.03 mumol/5 microliters/g body wt) was approximately 25% of that excreted in identically treated conventional mice. However, the levels of carcinogen-DNA adducts in the lungs and livers of conventional and germfree Balb/c mice were similar at the 24 and 48 h time points examined. HPLC analysis of hydrolysates of liver and lung DNA indicated that adducts derived from both N-hydroxy-6-aminochrysene and trans 1,2-dihydroxy-1,2-dihydro-6-aminochrysene metabolites were formed in the liver whereas only the latter adduct was detected in the lung. This contrasts with previous findings in preweanling mice where the adduct derived from the trans-1,2 dihydroxy-1,2-dihydro-6-aminochrysene metabolite was the single major adduct detected in both liver and lung DNA. The proportion of adducts derived from N hydroxy-6-aminochrysene was significantly greater in the liver DNA of germfree mice than in the liver DNA of conventional mice. PMID- 2315937 TI - Nasal lavage as a tool in assessing acute inflammation in response to inhaled pollutants. AB - The upper airway, especially the nose, is a major target of toxic damage. Nasal challenges followed by nasal lavage (NAL) have been applied to studies of hypersensitivity, in particular as a method to identify the allergen in patients with allergic situations such as rhinitis. The NAL method has not been extensively used to determine the effects of air pollutants on the upper airways in humans. Ozone is known to interact avidly with various tissues in the respiratory tract and to cause decrements in lung function tests. This oxidant pollutant has also been shown to induce inflammation in the lower airways of humans and animals. In this study, we have examined the effect of an acute (2 h) exposure of ozone at 0.4 ppm on the inflammatory response in the upper airways of 10 normal volunteers and compared these results to those obtained in the lower airways assessed by bronchoalveolar lavage (BAL). The results indicate significant increases in the number of polymorphonuclear neutrophils (PMN) in NAL immediately post exposure (7.7-fold). This increase is still detectable 18 h post exposure (6-fold) which is similar to the increase of PMN in BAL. Tryptase, released by mast cells was also increased in the NAL fluid immediately post exposure (2-fold). While the albumin level, which is an indicator of epithelial cell permeability, was elevated 18 h post exposure (1.5-fold), tryptase level, was not anymore elevated at that time point. Interestingly, several other markers of acute inflammation such as prostaglandin E2 (PGE2), C3a, urokinase-type plasminogen activator (U-PA), which were found to be significantly elevated in the BAL of the same group of subjects (18 h post exposure), were not elevated in the NAL either immediately post or 18 h post exposure. The level of uric acid, thought to be an important anti-oxidant molecule, was also unchanged in the NAL fluid but was elevated in the BAL fluid. Collectively the data suggest that NAL may serve as a sensitive and reliable technique to detect inflammation in the upper airways of subjects exposed to ozone. Moreover, in the case of this particular oxidant pollutant, the NAL seems to mirror the inflammatory response in the lower airways, 18 h post exposure, relative to the number of PMN and albumin levels. PMID- 2315938 TI - Metallothionein production: similar responsiveness of avian liver and kidney to chronic cadmium administration. AB - The accumulation of hepatic and renal Cd, Zn, Cu, and metallothionein (MT) was investigated in ringed turtle doves (Streptopelia risoria) chronically exposed to 3 different concentrations of dietary Cd. When only tissue-Cd was considered as an inducer of MT, kidney was found to be 35% as responsive as liver in producing MT. However, when all potentially relevant inducing metals (Cd + Zn + Cu) were taken into account, kidney was found to be 85% as responsive as liver. The greater production of MT/mol Cd in liver was accounted for mainly by a greater co accumulation of Zn/mol Cd in liver than in kidney. We conclude that the apparent tissue specificity in expression of MT may be overestimated by failure to consider fluctuations in multiple inducers. Variability in tissue-MT concentrations after chronic dietary Cd administration is best accounted for by a consideration of tissue-Cd, -Zn, and -Cu, rather than tissue-Cd alone. PMID- 2315939 TI - Effect of cadmium on membrane potential in isolated rat hepatocytes. AB - The effect of cadmium (Cd) on rat hepatocytes upon short term exposure was studied by focusing on the integrity of mitochondria and on the possible consequences of its disturbance, such as alterations in plasma membrane potential and loss of cell viability. Changes in the potential of mitochondrion and plasma membranes were monitored using [3H]triphenylmethylphosphonium (TPMP+) and [14C]SCN- probes, respectively. Isolated rat hepatocytes were exposed to increasing CdCl2 concentrations for short time periods (30-120 min). Cd measurement by atomic absorption showed that the cells efficiently accumulated Cd, as did mitochondria in situ. In CdCl2-treated cultures, it was observed that the release of TPMP+, which revealed a drop in the mitochondrial membrane potential, was time- and concentration-dependent, and that the first significant efflux was caused by a 30-min exposure to 89 microM CdCl2. No significant change in plasma membrane potential, as judged from the increase in the uptake of SCN-, was detected after 30 min, suggesting the greater precocity of the mitochondrial attack. Finally, the release of lactate dehydrogenase (LDH) occurred only after 2 h of exposure, reflecting ultimate stages of cell injury induced by Cd. These results suggest that Cd induces an alteration in mitochondrial function in hepatocytes which may lead to the loss of plasma membrane potential and cell viability. The study therefore adds further evidence of the role of mitochondria as primary targets in Cd-induced cytotoxicity. PMID- 2315941 TI - Pregnancy-induced mobilization of copper and zinc bound to renal metallothionein in cadmium-loaded rats. AB - Our investigations undertook to examine whether copper (Cu) and zinc (Zn) bound to renal metallothionein (MT) along with cadmium (Cd) in Cd-loaded rats can be mobilized during pregnancy and lactation. Rats of the Wistar strain were injected with Cd. Synthesis of MT containing Cd, Cu and Zn was induced in the kidneys. Concentrations of Cd and essential elements in blood plasma and organs (liver and kidneys) were compared among non-pregnant and pregnant, and Cd-loaded and non loaded rats at middle and late gestational days and after delivery. Cu bound to renal MT was decreased with gestational age, while Zn was slightly increased. The results indicate that Cu was mobilized and utilized even when the metal was bound to MT in the kidneys of dams. On the other hand, Zn bound to renal MT in Cd loaded rats was retained and not mobilized during pregnancy. The elution profile of renal MT on an SW column was changed from a typical renal to a mixed profile of renal and hepatic MTs as a result of decreased Cu content in MT. Plasma essential elements changed similarly with gestational age in both concentrations and distributions in non-loaded and Cd-loaded rats. These results indicate that the 3 metals bound to renal MT are dealt with differently during gestation and lactation, and Cu but not Zn is transferred to the fetus, independently of the Cd status of the dam. PMID- 2315940 TI - Induction of the P-450 I family of proteins by polycyclic aromatic hydrocarbons: possible relationship to their carcinogenicity. AB - The hypothesis has been put forward that mutagenic polycyclic aromatic hydrocarbons which induce the P-450 I family of cytochromes, the major enzyme system responsible for their activation, are likely to be carcinogenic. In order to test this hypothesis, rats have been pretreated with a number of polycyclic aromatic hydrocarbons of different mutagenic and carcinogenic potency and hepatic P-450 I activity was monitored using chemical probes such as the O-deethylation of ethoxyresorufin and metabolic activation of Glu-P-1 to mutagens, and immunologically employing polyclonal antibodies against purified rat P-450 I A1. All compounds studied enhanced P-450 I activity and induced P-450 I apoproteins but the extent of induction was very markedly different. The results are discussed with reference to the mutagenicity of these chemicals in the Ames test and their carcinogenicity in the classical mouse skin model. A relationship appears to exist between carcinogenicity of polycyclic aromatic hydrocarbons and their ability to induce hepatic P-450 I activity. PMID- 2315942 TI - Inhibition of catalase and epoxide hydrolase by the renal cystogen 2-amino-4,5 diphenylthiazole and its metabolites. AB - Subchronic feeding of 2-amino-4,5-diphenylthiazole (DPT) to rats results in the development of renal cysts and has been used as a model system to study polycystic kidney disease. Because previous studies revealed changes in renal enzymes following DPT administration, a possible direct effect of DPT and its phenolic metabolites on catalase and a related enzyme, epoxide hydrolase, was examined. Experiments with three in vitro systems (suspensions of rabbit renal tubules, rat kidney homogenates, and commercially obtained bovine liver catalase) revealed direct inhibition of catalase activity by the diphenolic metabolite (diOH- DPT: 2-amino-4,5di(4'-hydroxyphenyl)-thiazole), the known renal cystogen nordihydroquaiaretic acid (NDGA) 2-amino-4(4'-hydroxyphenyl),5-phenyl-thiazole (4OH-DPT), and the known catalase inhibitor 3-amino-1,2,4-triazole; DPT did not inhibit catalase activity. Following oral administration to rats of the DPT congeners, 4OH-DPT caused the greatest decrease in both renal catalase and cytosolic epoxide hydrolase activities and the shortest time to onset of cystic lesions. In vitro, mouse liver cytosolic epoxide hydrolase activity was substantially inhibited by 4OH-DPT and dioH-DPT, and NDGA, but not by 2-amino-4 phenyl,5-(4'-hydroxyphenyl)-thiazole (5OH-DPT) or DPT itself. Microsomal epoxide hydrolase (mEH) activity was inhibited by 4OH-DPT, unaffected by DPT or dioH-DPT, and stimulated 2-fold by 5OH-DPT. Finally, mEH activity was substantially higher in samples of normal human kidney than in samples of kidney derived from a patient with autosomal recessive polycystic kidney disease; no differences were observed in cEH activity in these samples. Although the role of altered catalase and epoxide hydrolase activities in cystogenesis is unknown, DPT-induced cyst formation is associated with loss of these enzyme activities in kidney tissue. To our knowledge, this is the first report of an in vivo diminution of cytosolic epoxide hydrolase activity by xenobiotics. PMID- 2315943 TI - An evaluation of the male reproductive toxicity of cathinone. AB - (-)-Cathinone is the major psychoactive component of khat plant (Catha edulis Forssk.). Khat has been shown to produce reproductive toxicity in human beings and experimental animals. However, the chemical constituents of khat leaves responsible for sexual dysfunction are not known. In the present study cathinone enantiomers have been investigated for their reproductive toxicity in rats. Cathinone produced a dose-dependent decrease in food consumption and suppressed the gain in body weight. There was a significant decrease in sperm count and motility and increase in the number of abnormal sperms in cathinone treated animals. Histopathological examination of testes revealed degeneration of interstitial tissue, cellular infiltration and atrophy of Sertoli and Leydig's cells in cathinone treated animals. Cathinone also produced a significant decrease in plasma testosterone levels of the rats. Although both enantiomers of cathinone produced deleterious effects on male reproductive system, (-)-cathinone was found to be more toxic. From this study it may be concluded that the cathinone content in khat may be partially or totally responsible for the reproductive toxicity in khat chewers. PMID- 2315944 TI - Protective effect of sodium molybdate against the acute toxicity of cadmium chloride. AB - Pretreatment of rats with Na2MoO4 (1.24 mmol/kg, once a day for 3 days, i.p.) partially protected them against the acute toxicity of CdCl2 (0.075 mmol/kg, once, s.c., 24 h after pretreatment with Na2MoO4). The survival number of rats per total number of rats in the CdCl2-dosed group was 10/10, 8/10, 6/10, 2/10 and 0/10 on 0, 1, 2, 6 and 18 days after treatment with CdCl2 whereas in the group where CdCl2 is given after pretreatment with Na2MoO4 it is 10/10 and 6/10 on 0 and 18 days. The body weight of CdCl2-dosed rats consistently decreased until their death while that of Na2MoO4-CdCl2-dosed rats similarly decreased up to 4 days after exposure to CdCl2 but then increased almost normally. In order to elucidate the mechanism of protective action of Na2MoO4 against the acute toxicity of CdCl2, cellular components such as DNA, inorganic cations and metallothionein were measured in the liver after exposure to CdCl2. The treatment with CdCl2 alone reduced K content and increased Ca content but pretreatment with Na2MoO4 prevented such alterations in the levels of those cations caused by CdCl2. Metallothionein content in the liver was significantly elevated in the CdCl2-treated groups as compared to saline controls although the protein content was higher in the Na2MoO4-CdCl2-dosed group than in the CdCl2-dosed group. There was no difference in the protein content of the liver between saline controls and the Na2MoO4-dosed group. This suggests that Na2MoO4 alleviated the acute toxicity of CdCl2 in the rat and the protective mechanism by the metal is in part related to the enhancement of liver Cd-metallothionein induction. PMID- 2315945 TI - 3-Methylcholanthrene induces differential inhibition of humoral and cell mediated immune responses in mice of different ages. AB - C57B1/6 mice aged 2-3 and 13-14 months were treated i.p. with 3 methylcholanthrene. A single dose of 25 mg/kg reduced primary antibody production to the T-dependent antigen sheep red blood cells by 20% in mice aged 2-3 months and by 90% in 13-14-month-old animals. The same treatment did not reduce antibody production to the T-independent antigen pneumococcal polysaccharide type III in young mice, but reduced this response by 50% in 13-14-month-old animals. Blastogenesis to concanavalin A, phytohemagglutinin and alloantigens, that is mediated by T lymphocytes, was consistently reduced in young animals but only marginally affected, when at all, in 13-14-month-old mice. Blastogenesis to lipopolysaccharide, mediated by B lymphocytes, was reduced in mice of both ages, though in older mice it was affected later than in younger animals. Addition of 3 methylcholanthrene in vitro increased T lymphocyte responses equally in mice of both ages and did not modify B lymphocyte proliferation. Results presented here show that older mice are not necessarily more susceptible to all types of immunosuppression induced by a xenobiotic like 3-methylcholanthrene and that the sensitivity of the different facets of the immune response can change with aging. PMID- 2315946 TI - Comparison of effectiveness of 3 dithiocarbamates on excretion and distribution of cadmium in rats and mice. AB - Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-methylbenzyl-D glucamine dithiocarbamate (MBGD), and sodium N-p-isopropylbenzyl-D-glucamine dithiocarbamate (PBGD), which were recently synthesized, were evaluated for their efficacy in the distribution and excretion of cadmium in rats and mice exposed to cadmium. Rats and mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 2 microCi 109Cd/one animal) and 3 days later, they were treated with the dithiocarbamates (400 mumol/kg) every other day for 2 weeks. These dithiocarbamates were effective in removing cadmium from the body without increasing the cadmium content in the kidney. After treatment with BGD, MBGD, and PBGD, cadmium was excreted mainly in the feces and the effect of MBGD and PBGD on the fecal excretion of cadmium was much larger than that of BGD. The treatment with these dithiocarbamates did not cause the redistribution of cadmium to brain, testes, and heart in rats and mice. The treatment of mice with PBGD decreased the concentrations of essential metals in liver, kidney, and brain. The extent of acute toxicity of the dithiocarbamates in mice was in the order PBGD greater than MBGD greater than BGD. PMID- 2315947 TI - Chronic inhalation effects of ethylene oxide on porphyrin-heme metabolism. AB - The effects of chronic ethylene oxide (EtO) inhalation on porphyrin-heme metabolism were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, hemoglobin content significantly decreased, and a normocytic and normochromic anemia was found. In the liver, cytochrome P-450 and protoheme significantly decreased but wet weight, microsomal protein and cytochrome b5 were not affected. The activity of delta-aminolevulinic acid (ALA) synthase increased while ALA dehydratase did not change. The activity of hepatic ferrochelatase decreased time-dependently. Uroporphyrin increased 37% and coproporphyrin tended to increase in the liver. The concentration of protoporphyrin in the liver and erythrocytes tended to increase. Coproporphyrin excretion in the urine showed a 5-6-fold increase while there was no significant increase in urinary ALA excretion. These results indicate that chronic inhalation of EtO causes alterations of hepatic porphyrin-heme metabolism as well as anemia and may affect mechanisms of adaptation to xenobiotics. PMID- 2315948 TI - Absorption, distribution, and elimination of a single oral dose of [14C]tri-o cresyl phosphate in hens. AB - The absorption, distribution, elimination, and metabolism of a single oral dose of 50 mg (4.6 microCi)/kg of uniformly phenyl-labeled [14C]tri-o-cresyl phosphate (TOCP) was investigated in adult chickens. Three treated hens were killed at each time interval: 0.5, 1, 2, and 5 days. TOCP was absorbed from the gastrointestinal tract and subsequently distributed throughout the body. Generally, the highest concentrations of radioactivity were associated with gastrointestinal tract parts, bile, kidneys, liver, and lungs. Most of the radioactivity (47%) was excreted in the combined fecal-urinary excreta during the first 12 h. Very small fractions of the dose were deposited in egg albumen and egg yolk, 0.12% and 0.24%, respectively during the 5-day study. After 5 days, 99% of the dose was eliminated in excreta. TOCP and its metabolites in bile and the combined fecal urinary excreta were analyzed by high-performance liquid chromatography and liquid scintillation spectrometry. TOCP and nine of its metabolites were identified. In the bile a TOCP active metabolite, saligenin cyclic-o-cresyl phosphate, was the predominant compound found compared to the parent compound in the excreta. These results suggest that in the hen TOCP is excreted slower than the rat and also undergoes metabolic activation. The absorption, elimination, and metabolic profile of TOCP in the hen may contribute to its sensitivity to delayed neurotoxicity. PMID- 2315949 TI - Determination of the effect of tridiphane on the pharmacokinetics of [14C] atrazine following oral administration to male Fischer 344 rats. AB - The absorption, distribution, metabolism and excretion of [14C]-atrazine was studied in male Fischer 344 rats administered a 30 mg [14C]-atrazine/kg of body weight oral dose with or without pretreatment with a non-radiolabeled oral dose of 60 mg tridiphane/kg of body weight. The objective of this study was to determine whether tridiphane had any meaningful effect on the pharmacokinetics and/or metabolism of atrazine in the rat. The 14C plasma time-course exhibited a mono-exponential decrease with an absorption and elimination half-life of approximately 3 h and 11 h, respectively for both treatment groups. In addition, at 72 h after the administration of [14C]-atrazine, approximately 93% of the administered radioactivity was recovered and the primary route of excretion was via the urine (67%) for both treatment groups. The feces accounted for approximately 18% of the dose, and less than 10% remained in the carcass, skin, and red blood cells (RBCs). The urine excreted in the first 24 h post-dosing contained approximately 57% of the administered radioactivity for both treatment groups. There were no appreciable differences in the metabolite distribution between treatment groups, and the major urinary metabolite of atrazine was found to be 2-chloro-4,6-diamino-1,3,5-triazine (II; 64-67%). Additionally, S-(2-amino 4-methylethylamino-1,3,5-triazin-6-yl)-mercapturi c acid (V; 13-14%), and S-(2,4 diamino-1,3,5-triazin-6-yl)-mercapturic acid (III; 9%) were tentatively identified based upon similar HPLC retention times as seen with synthesized standards. These data indicate that there are no meaningful differences in the absorption, distribution, metabolism, and excretion between rats administered only [14C]-atrazine and those administered both tridiphane and [14C]-atrazine. Therefore, it can be concluded that tridiphane has no meaningful effect on the pharmacokinetics and/or metabolism of atrazine in the rat. PMID- 2315950 TI - Toxicity of alkyldihydrofurans to metabolically active organs in the mouse. AB - Alkylfurans inflict toxicity in several mammalian species to lung, liver and kidney. Organ specificity of the alkylfurans is a sensitive function of the nature of the alkyl group. To determine if this toxicity requires an aromatic ring in the compound, we synthesized 4-methyl-2,3-dihydrofuran, 4-ethyl-2,3 dihydrofuran and 4-pentyl-2,3-dihydrofuran and determined their toxicity to lung, liver and kidney in mice. Lung damage was evaluated by light microscopy and the incorporation of [14C]thymidine into lung DNA. The results indicated that 4 methyl-2,3-dihydrofuran and 4-ethyl-2,3-dihydrofuran were toxic to the lung whereas 4-pentyl-2,3-dihydrofuran did not produce lung toxicity. Histological examination of liver sections revealed that 4-ethyl-2,3-dihydrofuran induced vacuolar degeneration of hepatocytes. Kidney toxicity was evaluated by light microscopy and determining plasma urea levels. Both 4-ethyl-2,3-dihydrofuran and 4-pentyl-2,3-dihydrofuran exhibited kidney toxicity, while equimolar doses of 4 methyl-2,3-dihydrofuran did not damage the kidney. A quantitative comparison of the nephrotoxicity of 4-pentyl-2,3-dihydrofuran with the corresponding aromatic compound 3-pentylfuran was made. We also sought to determine if renal injury resulting from these 2 agents is related to their oxidative metabolism. Uptake of organic ions by kidney slices and plasma urea nitrogen levels were used to assess renal function. 3-Pentylfuran caused greater renal injury than an equimolar dose of 4-pentyl-2,3-dihydrofuran. Phenobarbital pretreatment protected mice against 3 pentylfuran-induced nephrotoxicity. Cotreatment with piperonyl butoxide did not affect renal injury resulting from 3-pentylfuran. N-octylimidazole significantly reduced 3-pentylfuran-induced nephrotoxicity as well as that caused by 4-pentyl 2,3-dihydrofuran. These results point to metabolic activation as a basis for the nephrotoxicity induced by both compounds. PMID- 2315951 TI - Depression of glutathione by cold-restraint in mice. AB - The effects of cold-restraint as a physiological stressor on the glutathione (GSH) content of the liver and other tissues were examined in male mice. Mice of the ICR, NIH, ND/4, and B6C3F1 strains subjected to cold-restraint for 2 or 3 h experienced a loss of hepatic GSH concentrations ranging from approximately 15 to 50%. Though 3 of these strains (ICR, NIH, and B6C3F1) experienced hypothermia as result of the cold-restraint treatment, with average decreases in core body temperature ranging from 3.3 to 9.8 degrees C, hepatic GSH levels were depressed in the ND/4 mouse in the absence of changes in core body temperature. The ability of cold-restraint as a stressor to diminish hepatic GSH therefore could not be attributed simply to hypothermia. The decrease in hepatic GSH from cold-restraint in ND/4 mice was paralleled by a decrease in non-protein sulfhydryl (NPSH) content of the liver. In addition to its effects on liver GSH and NPSH concentrations, 1.5 h of cold-restraint stress significantly depressed plasma, heart, kidney, and lung NPSH concentrations. The extent of NPSH depression was equivalent to the GSH depression in the liver, heart, and kidney, despite the observation that the normal contribution of GSH to total NPSH content in these tissues ranged from a high of 89% (liver) to a low of 49% (heart). These results with cold-restraint in the ND/4 mouse suggest that other stressors may significantly depress cellular concentrations of GSH and other thiols, and may thereby render the affected tissues more susceptible to the toxicity of free radicals, electrophilic xenobiotic metabolites, or reactive oxygen species. PMID- 2315952 TI - Intracellular cadmium mobilization sequelae. AB - The consequences of the mobilization of aged intracellular cadmium from its in vivo deposits in mice by chelating agents were examined. The chelating agents used were BAL, sodium N-benzyl-D-glucamine dithiocarbamate (NaB), Diisopropyl meso-2,3-dimercaptosuccinate(Di-PDMS) and sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate(4-Me0), all previously shown capable of causing statistically significant decreases in either renal or hepatic cadmium burdens in rodents. They were given at a level of 400 mumol/kg (i.p.) daily for 10 days to mice previously loaded with a total of 10 mg CdCl2.2.5 H2O/kg. Under these conditions a significant decrease in the renal cadmium level occurred following treatment with BAL, NaB, and 4-MeO; hepatic cadmium levels decreased significantly following treatment with NaB and 4-MeO. Pathological examination of the kidneys, liver, and testes in these animals showed that chelate mobilization of the cadmium produced no noticeable changes in the histopathology of these organs in comparison with that observed for the animals which had been given only cadmium and had undergone no chelate treatment. The results suggest that the mobilization of such aged cadmium from in vivo deposits need not result in any deleterious changes in the kidneys, liver or testes. PMID- 2315953 TI - Inhibition of 12-O-tetradecanoylphorbol-13-acetate-enhanced transformation in vitro by inhibitors of phospholipid metabolism. AB - The effects of some inhibitors of phospholipid metabolism were studied using a two-stage transformation assay system in vitro with 3-methylcholanthrene (3-MC) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in BALB/3T3 cells. Inhibitors of phospholipid metabolism such as hydrocortisone (HC), p bromophenacyl bromide (BPB), nordihydroguaiaretic acid (NDGA), quercetin and indomethacin (IM) were used. They were demonstrated to inhibit strongly TPA promoted transformation. In particular, HC at 1 microgram/ml inhibited the in vitro transformation completely. All the inhibitors used inhibited transformation in a dose-dependent manner. The results suggest that phospholipid metabolism is important for the promotion stage of transformation in BALB/3T3 cells. PMID- 2315954 TI - Modulation of the course of CCl4-induced liver injury by the anti-calmodulin drug thioridazine. AB - Thioridazine (TDZ) administration to rats (50 mg/kg i.p.) 6 or 10 h after CCl4 treatment (1 ml/kg in olive oil i.p.) partially prevented necrogenic effects of this compound at 24 h but not at 72 h. TDZ did not have inhibitory effects on CCl4 activation, covalent binding (CB) of reactive metabolites to cellular constituents or CCl4-induced lipid peroxidation (LP). Moreover, TDZ had enhancing effects on both LP and CB. TDZ was able to increase protein and phospholipid synthesis and slightly but significantly enhanced protein but not phospholipid degradation in livers from control rats. TDZ administration decreased calcium liver content in CCl4-poisoned animals but did not change the intensity of CCl4 induced fatty liver. TDZ lowered body temperature in CCl4-treated animals during the 24 h observation period. These results and previous studies from our laboratory suggest calcium and calmodulin (CaM) participation in the CCl4 necrogenic effects on the liver but not in the hepatotoxin-induced fatty liver. TDZ-lowering effects on body temperature might also be a determinant in the delaying effects of this drug on the onset of CCl4-induced necrosis. Present experiments did allow discrimination between these two or other possible mechanisms for TDZ modulation effects. PMID- 2315956 TI - Lack of an effect of saxitonin on the contractility of isolated guinea-pig trachea, lung parenchyma and aorta. AB - The effects of saxitonin were investigated in guinea-pig tracheal rings, lung parenchymal strips and aorta rings. Tracheal rings were used both with epithelium present and with it removed. Aorta rings were used both with endothelium present and with it removed. Saxitoxin, 1 pM to 0.1 microM, did not alter the resting tension of either airway tissues or aorta. Also 0.1 microM saxitonin did not reduce tension of tracheal rings contracted by 10 microM carbachol, parenchymal strips contracted by 100 microM acetylcholine or by 10 microM histamine, or aorta rings contracted by 10 microM norepinephrine. Responses of tracheal rings to 0.03 10 microM carbachol added cumulatively were not altered by 0.1 microM saxitoxin (EC50 with epithelium: 1.11 +/- 0.48 microM control, 2.01 +/- 0.71 microM with saxitoxin; EC50 without epithelium: 2.83 +/- 0.55 microM control, 2.05 +/- 0.58 microM with saxitoxin). Also, 1 microM saxitoxin did not alter contractions of parenchymal stirps to cumulatively added acetylcholine (EC50: 3.47 +/- 1.06 microM, control; 3.98 +/- 1.19 microM with saxitoxin), histamine (EC50: 0.83 +/- 0.24 microM, control; 0.60 +/- 0.13 microM with saxitoxin); or of aorta strips to norepinephrine with endothelium (EC50: 1.78 +/- 0.80 microM, control; 0.74 +/- 0.21 microM with saxitoxin) or without endothelium (EC50: 2.18 +/- 0.78 microM, control; 1.42 +/- 0.62 microM with saxitoxin). Thus, saxitoxin did not significantly alter contractile activity of airways of large arteries in vitro. PMID- 2315955 TI - Cadmium cytotoxicity correlates with the changes in glutathione content that occur during the logarithmic growth phase of A549-T27 cells. AB - Correlation of cadmium cytotoxicity with cellular glutathione content as it changes during cell growth was examined in human lung carcinoma A549-T27 cells. Cellular glutathione content was found to increase rapidly during the first 24 h of subculture, which includes the lag and early log phases of growth, and to decrease continuously thereafter. Glutathione content reached its lowest level at 108 h of subculture. This period of glutathione decrease represented most of the logarithmic phase of cell growth. Cells exposed to cadmium at different times during the logarithmic growth phase showed differential sensitivity. Cells with the higher initial glutathione content that occurs at the early period of the logarithmic growth phase were cadmium-resistant relative to those of lower glutathione content found at the later period of the logarithmic phase. A high correlation (r = 0.82) between cadmium sensitivity and glutathione content was found, which suggests that intracellular glutathione content is an important determinant of overall cadmium cytotoxicity. PMID- 2315957 TI - Effects of rhodamine 6G on the mitochondrial ultrastructure of mouse spermatocytes. AB - Effects of rhodamine 6G on spermatocyte mitochondria were assessed in BALB/c mice in vivo. Four groups of mice were given rhodamine 6G doses of 0.0, 0.3 and 0.5 and 0.8 mg.kg-1.d-1 i.p. for 5 days. On the 5th day after the last day of dye administration, the mice were killed and testicular tissue was prepared for electron microscopy. Exposure to rhodamine 6G resulted in dose-dependent effects, primarily intracristal expansion of mitochondria. PMID- 2315958 TI - Cytotoxic T-lymphocyte and NK responses in mice treated prenatally with chlordane. AB - It has been reported previously that BALB/c mice, treated in utero with chlordane, showed increased survival to influenza A/PR/8/34 [H1N1] (influenza) virus as young adults. To determine the possible role of cell-mediated immunity (CMI) on this effect, cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell activities were assessed on chlordane-exposed offspring at 100 and 200 days post partum. The CTL response of these offspring showed no significant change from that obtained from their sex- and age-matched control counterparts exposed prenatally to the vehicle. NK responses of chlordane-exposed female offspring were significantly higher at 100 days of age but not at 200 days of age. Although male offspring that were exposed to chlordane prenatally showed no difference in NK cell activity at 100 days of age, NK cell activity was significantly less in chlordane-treated animals than controls at 200 days of age. Thus, prenatal treatment of mice with chlordane had varying effects on the NK cell activity of adult offspring, depending on the sex and age of the animal. It is concluded that the previously reported increase in survival to influenza is due to a resolution of the infection by normal CTL and NK cell activities coupled with a decrease in delayed-type hypersensitivity (DTH)-mediated pathology. PMID- 2315959 TI - Increased levels of protein- and lipid-bound sialic acids in the renal cortex of rats injected with low doses of gentamicin. AB - Administration of the aminoglycoside antibiotic, gentamicin, even at therapeutic doses, causes renal lysosomal phospholipidosis. We now report that protein- and lipid-bound sialic acid levels are increased significantly in a time-dependent fashion in the renal cortex of rats injected with gentamicin (10 mg/kg body wt. per day) for 4-10 days and a significant relationship could be observed between these two parameters. This elevation was not due to tissue regeneration, since it was not observed in cisplatin-treated animals. PMID- 2315960 TI - The protective effects of glutathione against methylmercury cytotoxicity. AB - Mouse neuroblastoma cells exposed to 2.5 and 5.0 microM methylmercury for 24 h appeared rounded with the loss of processes. Immunohistochemical staining directed against beta-tubulin revealed severe alterations in microtubular architecture. Non-membrane-bound condensation product was visualized ultrastructurally in the treated cells and appeared similar to what was seen histochemically. Reduced and oxidized glutathione levels suggest that methylmercury may manifest its deleterious effects via oxidation of tubulin sulfhydryls, and by alterations due to peroxidative injury. Cells exposed to methylmercury showed a decrease in glutathione peroxidase activity. Simultaneous administration of 10 mM glutathione with 2.5 and 5.0 microM methylmercury dramatically prevented cell injury. PMID- 2315961 TI - Effects of activators and inhibitors of protein kinase C on two-stage transformation in BALB/3T3 cells. AB - To determine the relationship between protein kinase C and the promotion of carcinogenesis, we investigated the effects of activators and inhibitors of protein kinase C on two-stage transformation in BALB/3T3 cells. Diacylglycerols, which are activators, and specific inhibitors, such as palmitoyl-DL-carnitine chloride (PC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H 7), and staurosporine (ST) were used. Treatment with diacylglycerols enhanced focus formation in 3-methylcholanthrene (3-MC)-initiated cells, but not as much as 12-O-tetradecanoylphorbol-13-acetate (TPA). PC and H-7 inhibited TPA-enhanced transformation by 76 and 79%, respectively. ST, the most potent inhibitor of protein kinase C, had a low inhibitory effect on transformation at non-toxic doses (33% inhibition). The results suggest that protein kinase C may play an important role in the process by which transformation is promoted in BALB/3T3 cells. PMID- 2315962 TI - Pteridine modulation of lead inhibition of uroporphyrinogen synthesis in erythroid precursor cells. AB - The role of nutritional factors on heme synthesis and their influence on the development of anemia in the bone marrow during lead exposure is unclear. Previous reports suggested that pteridines could regulate the formation of uroporphyrinogen, a step midway along the heme synthetic pathway. Studies were undertaken to determine if pteridines could modulate lead inhibition of uroporphyrinogen synthesis in erythroid precursor cells. Pteroylpolyglutamates of various glutamate chain lengths were tested for the ability to protect against lead inhibition of uroporphyrinogen I (URO) synthase prepared from murine erythroleukemia cells (MELC). Pteroylpentaglutamate, the major endogenous polyglutamate form by chain length found to be present in MELC, afforded rapid and specific protection of URO synthase against lead inhibition. MELC are expected to be a useful in vitro model for studying the role of endogenous folates on uroporphyrinogen synthesis and heme formation in erythroid precursor cells following lead exposure. PMID- 2315963 TI - Metallothionein induction and metal homeostasis in rainbow trout hepatocytes exposed to mercury. AB - Rainbow trout hepatocytes were exposed to a sublethal concentration of mercury (Hg) (100 nM) for 0, 5, 10, 15, 20, 25, 30 and 35 h at 15 degrees C. The hepatocytes were found to accumulate appreciable quantities of Hg. The presence of Hg led to elevated Ca, Cu and Zn levels in cells. Hg was bound mainly to low molecular-weight components, although it induced the synthesis of metallothionein (MT). The results suggest that when hepatocytes are exposed to low levels of Hg, MT does not play a significant role in the sequestration of the metal. The elevated cellular Cu and Zn levels could be associated with the induction of MT. PMID- 2315964 TI - United States and Denmark: different approaches to health care and family planning. AB - The findings of this study suggest that, compared to the United States, Danish health care policies and family planning services delivery systems are, in the aggregate, more conducive to the promotion of effective contraceptive practice, more instrumental in conveying information to high-risk groups, and more successful in reducing the incidence of unintended pregnancies and induced abortions. One of the major reasons for this difference may stem from the positive and nonambivalent climate of public opinion about sexuality in Denmark and the manner in which health care and family planning services are delivered to all segments of the population regardless of age, income, or location of residence. Research in reproductive behavior is greatly facilitated by the existence of automated population registers. PMID- 2315965 TI - Family planning in Rwanda: status and prospects. AB - This article analyzes the status and future prospects of family planning in Rwanda. The use of traditional contraceptive methods is examined and major constraints to modern contraceptive use are discussed, both for potential users (low demand) and family planning delivery systems (poor supply). Current contraceptive prevalence, as well as evidence of potentially higher demand, are analyzed. Contraceptive prevalence for modern methods is estimated at 3-4 percent, for 1988, of women of reproductive age who are at risk of exposure to conception. An attempt is also made to target future contraceptive prevalence rates needed to attain specific levels of fertility. Finally, the prospects for family planning as well as recommendations to increase contraceptive use are reviewed. PMID- 2315966 TI - Fertility and family planning in Jordan: results from the 1985 Jordan Husbands' Fertility Survey. AB - The 1985 Jordan Husbands' Fertility Survey (JHFS) was designed to assess husbands' attitudes and behavior toward fertility and family planning. The 1985 JHFS was a follow-up survey to obtain data from husbands of women who were currently married in the 1983 Jordan Fertility and Family Health Survey (JFFHS). The results from the 1985 JHFS point to the usefulness of collecting fertility and family planning information from husbands. These findings showed that nearly 40 percent of the husbands do not believe in practicing contraception, and more than 50 percent of the husbands report that family size should be "up to God." How program officials address these issues will be important for the future success of the family planning program in Jordan. PMID- 2315967 TI - Infant feeding practices in Thailand: an update from the 1987 Demographic and Health Survey. AB - Data from the Thai Demographic and Health Survey, conducted in 1987, confirm evidence from earlier surveys that the decline in the duration of breastfeeding evident during the 1970s came largely to a standstill in the 1980s. In addition, the proportion initiating breastfeeding, while high throughout the period, has increased to the point where, at the national level, it is now close to universal. These changes coincide with efforts, primarily undertaken or coordinated by the Ministry of Public Health, to promote breastfeeding and discourage use of breast milk substitutes. While substantial socioeconomic differentials in the duration of breastfeeding exist, initiation is common even among the groups that breastfeed for the shortest period of time. Breastfed children are generally given supplemental foods or liquids at very early ages. It is common to breastfeed children relatively frequently during the day and evening. Bottles with nipples are used to provide supplementary food to breastfed children by a substantial proportion of mothers. Most use of bottles with breastfed children is not for the provision of infant formula but for other types of supplemental food. PMID- 2315968 TI - Guatemala 1987: results from the demographic and health survey. PMID- 2315969 TI - Cis- and trans-isomers of doxepin and desmethyldoxepin in the plasma of depressed patients treated with doxepin. AB - Plasma levels of doxepin and desmethyldoxepin were measured in split samples of 20 depressed patients treated with doxepin by using a conventional extraction and gas chromatography method on a packed column (method 1) and derivation of secondary amine and gas chromatography on a capillary column, allowing the separation and simultaneous quantitation of the cis- and trans-isomers of the two compounds (method 2). We have found that significantly higher levels of desmethyldoxepin and of total drug are detected in plasma when the two isomers are separated and measured by method 2. We concluded that the plasma levels of doxepin reported in most previous studies were underestimated since the cis- and trans-isomers were not separated and included in the total drug concentration. Because the activity of the two isomers is different and their proportion varies in individual patients, we suggest that in future studies correlating plasma levels and the clinical effects of doxepin, both the cis- and the trans-isomers of doxepin and desmethyldoxepin be determined. PMID- 2315970 TI - Single-dose cyclosporine pharmacokinetics in various biological fluids of patients receiving allogeneic marrow transplantation. AB - The clinical usefulness of cyclosporine is hampered by dose-limiting toxicities to the kidney that are not predicted by drug levels in serum or whole blood. Because of its lipophilic nature, circulating plasma lipoproteins may play a role in drug disposition. This study characterized the pharmacokinetic parameters of a single 2-mg/kg i.v. infusion of cyclosporine in the whole blood, plasma, high density (HDL), low-density (LDL), and very low-density (VLDL) lipoprotein fractions of nine patients before bone marrow transplantation. The dose- and protein-corrected area under the concentration-time curve in whole blood; plasma; and HDL, LDL, and VLDL compartments were 44.6 +/- 11.3, 19.2 +/- 2.4; 33.6 +/- 12.3, 49.0 +/- 19.9, and 17.5 +/- 9.0 ng h/ml, respectively. The mean half-life of the drug from the VLDL fraction was significantly less than from the other biologic fluids. The systemic clearance rate of cyclosporine was greater in the total plasma or VLDL fractions compared with whole blood and the HDL and LDL fractions. The HDL-cyclosporine clearance inversely correlated with the serum creatinine (r = -0.71; p less than 0.05) and total bilirubin levels (r = -0.76; p less than 0.05). The plasma half-life and volume of distribution directly correlated with fasting HDL cholesterol levels (r = 0.94 and 0.99; p less than 0.01). Correlations between pharmacokinetic parameters and lipid fractions suggest a role of lipids in the distribution of cyclosporine. These data may be useful in the development of guidelines for therapeutic drug monitoring of cyclosporine in the transplantation population. PMID- 2315972 TI - Comparison of two infusion methods for pharmacokinetic monitoring of gentamicin. AB - Gentamicin is commonly administered by intermittent infusions using a gravity flow or a mechanical device. The primary objective of our study was to compare the pharmacokinetic data in patients receiving gentamicin infusion by a syringe pump and a new controlled-release membrane infusion device. The membrane device consists of a drug and a fluid chamber separated by a 0.2-micron proprietary membrane; drug transfer is based on electrodiffusion across the membrane. Ten patients (mean age 50 years) received the same dose of gentamicin, separated by a 24-h interval, from two devices. Differences in serum concentrations, distribution volume, and half-life were not statistically significant. However, time for complete delivery (0.9 +/- 0.4 h for membrane device vs. 0.5 h for syringe pump) and calculated dosage requirements (10.9 +/- 6.3 vs. 9.6 +/- 5.5 mg/h) to achieve peak of 7 and trough of 1 microgram/ml were significantly different (p less than 0.05). Thus, the infusion method for gentamicin can have a significant influence on its pharmacokinetic monitoring. PMID- 2315971 TI - Effect of ponsinomycin on single-dose kinetics and metabolism of carbamazepine. AB - The effect of ponsinomycin (or miocamycin), a new macrolide antibiotic, was investigated on the pharmacokinetics of carbamazepine (CBZ) administered as a single dose in healthy volunteers. Disposition of the active 10,11 epoxycarbamazepine (ECBZ) was investigated as well. For each compound both total and free plasma concentrations were measured. A moderate (+13%) but statistically significant (p less than 0.05) increase of CBZ total area under the curve (AUC), was observed in the presence of ponsinomycin, accompanied by a 26% decrease (p less than 0.01) in the AUC of its metabolite. There was a tendency toward an increase in AUC of unbound CBZ, although it was not statistically significant. Together these data suggest that formation of ECBZ is inhibited in the presence of ponsinomycin. The relative importance of the epoxy-diol metabolic pathway being increased at steady state due to autoinduction, results of this study suggest that CBZ plasma levels should be carefully monitored in patients receiving ponsinomycin. PMID- 2315973 TI - The pharmacokinetics of omeprazole in humans--a study of single intravenous and oral doses. AB - The pharmacokinetics of omeprazole, hydroxyomeprazole, omeprazolesulfone, and "remaining metabolites" have been studied in eight young healthy subjects following an acute i.v. and oral dose of 10 and 20 mg of 14C-labeled drug, respectively. The oral dose was given as a buffered solution. Two subjects exhibited essentially higher and more sustained plasma levels of omeprazole than the others. This was due to a higher bioavailability, lower clearance, and longer t1/2 of omeprazole in these two subjects. Maximum concentration (0.7-4.6 mumol/L) was reached between 10 and 25 min after oral dosing. The median bioavailability was 39% (25-117%) and the median systemic plasma clearance was 624 ml/min (range of 59-828 ml/min). The corresponding t1/2 for the i.v. dose was 35 min (16-150 min) and 39 min (14-186 min) after oral administration. The drug was rapidly distributed to extravascular sites (mean t1/2 lambda 1 = 3.0 +/- 0.8 min). Mean Vss was 0.23 +/- 0.04 L/kg. Low systemic clearance of omeprazole was associated with a decreased formation rate of hydroxyomepraxole and "remaining metabolites" while omeprazolesulfone formation seemed to be less affected. However, there was a clear-cut correlation between the t1/2 of omeprazole and of its omeprazolesulfone metabolite, indicating that the elimination of these two compounds is mediated by the same isoenzyme. The mean urinary recovery of the radioactive dose during 96 h was 78.3 +/- 2.3 and 75.7 +/- 2.6% for the i.v. and oral dose, respectively. Insignificant amounts were due to unchanged drug and omeprazolesulfone. The excretion of hydroxyomeprazole during the first 12 h varied between 4.6 to 15.5% of a given dose. The mean recovery of radioactivity in the feces was 19.3 +/- 3.1% of a given i.v. dose and 18.2 +/- 2.3% when given orally. It is concluded that omeprazole is mainly eliminated metabolically and that there is a substantial interindividual variation in the rate of formation of primary and secondary metabolites. This variation in omeprazole disposition is probably of limited clinical importance. The half-life, with a maximum of approximately 3 h, is too short to cause accumulation when the drug is administered in a once-daily regimen. PMID- 2315974 TI - Therapeutic drug monitoring: improved performance through educational intervention. AB - A pilot study done at our institution and previous studies in the literature indicate that therapeutic drug monitoring (TDM) is frequently performed without a proper indication. In addition, samples are often improperly collected or interpreted by physicians. The purpose of this study was to determine if a pharmacy-based educational intervention could positively influence the performance of TDM in a teaching institution. A cost-savings analysis on the reduction of drug levels not indicated or improperly sampled was also performed. The study consisted of a preliminary data collection period, an educational intervention, and a postintervention data collection period. The pre- and posteducational intervention periods consisted of a 1-month concurrent review of aminoglycosides, digoxin, and theophylline serum levels. The educational intervention consisted of in-service programs and newsletter. There were 188 and 211 serum drug levels analyzed during the pre- and postintervention periods, respectively. Overall, the educational intervention significantly increased the number of drug levels obtained for rational indications, correctly sampled and appropriately interpreted by physicians (p less than 0.001, chi 2 analysis). Cost savings associated with this program was +2,788 in patient charges (+559 in hospital costs) per month. This study demonstrated that TDM may be significantly improved through education. PMID- 2315975 TI - Therapeutic monitoring of albendazole: a high-performance liquid chromatography method for determination of its active metabolite albendazole sulfoxide. AB - A sensitive and specific reversed-phase high-performance liquid chromatography (HPLC) method is described for the quantitative determination of albendazole sulfoxide (ASOX); since albendazole sulfone (ASON) appears only in small amounts and albendazole (ABZ) normally does not appear in human plasma, only a qualitative determination of ASON and ABZ was made in human plasma. Plasma samples were extracted three times using ethylacetate and petroleum benzine; this yielded optically clear samples which after evaporation were dissolved in the HPLC solvent and injected onto an RP-C18 column, with ultraviolet detection at 290 nm. The detection limit of the main metabolite ASOX was 50 nM and that of ASON was 100 nM. The intraday coefficient of variation for ASOX was 3.3% at a concentration of 2.2 microM, and the interday coefficients of variation were 14.5, 7.3, and 9.1% at ASOX concentrations of 0.5, 2.5, and 5.0 microM, respectively. Calibration was linear in a concentration range of 0.05-12 microM for ASOX and 0.1-8 microM for ASON, respectively. Pharmacokinetic data of a patient with echinococcosis are presented. PMID- 2315976 TI - High-performance liquid chromatographic determination of methotrexate in plasma. AB - A procedure for the determination of methotrexate in human plasma is reported. The analysis involved extraction of methotrexate as an ion pair in ethyl acetate. Reconstituted residue was analyzed using reverse phase C-18 column and a mobile phase consisting of acetate buffer (87%), methanol (6.5%), and acetonitrile (6.5%). The methotrexate recovery range was 95-97%. Theophylline was used as internal standard with a recovery of 96%. The intraday coefficient of variation for the assay ranged from 1.8-3.0%, while interday variation coefficient range was 3.5-3.7%. The method is selective, reproducible, and covers a wide range of methotrexate concentrations in patient's plasma. PMID- 2315977 TI - Radioimmunoassay of digoxin in serum using monoclonal antibodies and assessment of interference by digoxin-like immunoreactive substances. AB - We used 7 monoclonal antibodies (MoAbs) and one polyclonal antibody to develop radioimmunoassays (RIAs) for digoxin in serum or plasma. These RIAs were tested for measuring apparent digoxin concentrations in serum from patients receiving the drug, from normal individuals, and in cord blood plasma. We found that two MoAbs cross-reacted significantly with substances in cord blood. The magnitude of cross-reactivity was dependent on the incubation time and temperature. Under equilibrium conditions, one antibody gave apparent digoxin values in cord blood plasma averaging 2.15 ng/ml. We suggest that this cross-reactivity is partially due to progesterone and 17-hydroxyprogesterone in cord blood plasma. The antibody that shows high cross-reactivity with digoxin-like immunoreactive substances may prove a useful tool for studies dealing with characterization of the cross reacting compounds. PMID- 2315978 TI - A dry-strip immunometric assay for digoxin on the Ames Seralyzer. AB - We evaluated the Ames Seralyzer III with a new reagent and drystrip test for assay of digoxin. Assay precision was acceptable in the therapeutic range. Within run imprecision (coefficient of variation, n = 20) was 7% at 0.9 ng/ml (1.2 nM) and 3.5% at 1.9 ng/ml (2.4 nM); run-to-run imprecision was 7.6% at 0.8 ng/ml (1.0 nM) and 5.7% at 2.1 ng/ml (2.7 nM). The method is very reproducible and is linear between 0.5 and 4.3 ng/ml (0.6-5.5 nM). The assay performed well with patient samples, with Abbott TDx used as the reference procedure. Bilirubin up to 16 mg/dl (273 microM) and hemoglobin up to 11 g/l do not cause interference. Digoxin like immunoreactive factors cause minimal interference. Some digoxin metabolites such as monodigitoxoside, bis-digitoxoside, and digoxigenin cross-react with the digoxin antibody. Patients on spironolactone have falsely increased digoxin values. The new digoxin assay is easy to perform and uses 30 microliters serum; the result can be reported in 15-20 min. PMID- 2315979 TI - Using clinical data to determine vancomycin dosing parameters. AB - The serum concentrations and pharmacokinetic parameters produced from standard doses of vancomycin were evaluated in 22 patients. The mean (+/- SD) half-life, clearance (Cl), and volume of distribution, respectively, were 6.2 (+/- 1.9) h, 79.2 (+/- 34.3) ml/min, and 0.54 (+/- 0.23) L/kg. Geometric regression analysis was used to determine significant correlations between Cl and creatinine clearance (CrCl) (p less than 0.001). The dosing method developed is based on the pharmacokinetic parameters of vancomycin derived from our patient data and the relationship between Cl and CrCl described by the following equation, Cl = (0.674) (CrCl) + 13.45 (r = 0.703). Predictive performance measures were used to compare our dosing method with that of the Matzke nomogram. Our method was found to be less biased and more precise in regards to predicted half-life and volume of distribution, while less biased with no difference in precision in regard to predicting clearance. We plan to use this dosing method at our institution to provide a more individualized initial dosing regimen for vancomycin. Other institutions may wish to use a similar approach to design a dosing nomogram specific for their patient population. PMID- 2315980 TI - Falsely high-trough cyclosporine levels in capillary samples due to topical contamination. PMID- 2315981 TI - [Geriatrics threatened or a threat?]. PMID- 2315982 TI - [The elderly and the use of home care. Past, present and future]. AB - Home help is supposed to be one of the most important instruments for the sustained independency of the elderly. It is true that home help is a general provision, but because of the ongoing ageing of the population, it becomes a provision with mainly elderly clients (60%). In percentages of population the importance of home help increases with age and achieves a maximum for people of 80-84 years (15%). Clients living by themselves are the most important group (70%). Two thirds of the elderly clients have a public pension as (maximum) income, which explains the low contribution of client fees to the total costs. On average, they account for 14.7% of the costs for alpha service and 7.6% of the costs for traditional home help. Clients receive home help for more than three years, which is not only influenced by marital status (clients living by themselves 50% longer than other households), but also by age (the older, the longer). Within the group of elderly clients we found a positive relation between clients' age and total help in hours per week and in years of care. The ongoing greying will cause an increase in the number of clients with an average of 1.8% per year until the end of the century. Improvement of efficiency and diversification of provisions could partly mitigate the expected financial pressure, but because of the (intended) incorporation of home help services in the social insurance package (AWBZ), policy makers will have to pay attention to the financial consequences of population ageing for the home help services. PMID- 2315983 TI - Developing and promoting managerial talent. AB - 1. Developing and promoting managerial talent through the use of power and influence, mentoring, and empowerment is essential for seizing opportunities to successfully meet nursing challenges. 2. Power is the ability to affect outcomes, whereas influence is the process of modifying behavior. 3. Mentoring has several advantages: reduction of employee turnover; cultivation of talented employees; and maintenance of organizational goals and traditions. PMID- 2315984 TI - Keep what you've got: the role of the manager in nurse retention. AB - 1. The nursing shortage of today differs significantly from shortages of the past. A decrease in the nursing pool compounded with an increased variety of career opportunities for women are some of the major contributing factors. 2. Early attempts to solve the shortage focused primarily on recruitment strategies. 3. In these times of cost containment, agencies cannot afford substantial staff turnover. Thus, retention of staff has far-reaching implications. 4. Although the preparation of the nurse manager has improved, there is still a disequilibrium between the nurse manager and appropriate management skills. PMID- 2315985 TI - Digital replantation. Using the ninety-ninety intraosseous wiring technique. AB - 1. In ninety-ninety intraosseous wiring, two 26-gauge intraosseous wires are placed perpendicular to each other through bone. This technique requires slight exposure to obtain rigid fixation, and the patient can expect relatively unhindered rehabilitation using early digit motion. 2. Because the procedure is long and tedious, two surgical teams, each with its own circulating and scrub nurses, are preferred. 3. Ninety-ninety intraosseous wiring is less prominent than plates or screws, it has less risk that adhesions will develop, and, theoretically, less bone is devascularized. PMID- 2315986 TI - Designing a state-of-the-art operating room complex. AB - 1. When designing a new operating room complex, it is important to remember that, with a life expectancy of 15 years or more, you must take into account not only your current needs, but also anticipate those of the future. 2. The OR facility needs to be designed both for patients and providers: provide private, comfortable surroundings for your patients that are efficient and conducive to developing an enjoyable work environment for your staff. 3. Be sure to solicit input from various department managers as well as physicians during the initial design phases so that all needs may be met. In addition, ensure that state guidelines are satisfied. PMID- 2315987 TI - Hair clipping superior to preoperative shave. PMID- 2315988 TI - Innovations in liposuction. PMID- 2315989 TI - The future is up to us. PMID- 2315990 TI - Hemispherectomy--a radical solution. AB - 1. Hemispherectomy, a procedure where half of the brain is removed, is one of the most radical surgeries performed. One of the few medical conditions to warrant such a procedure is intractable seizures in infantile hemiplegia. 2. Children on whom hemispherectomies are performed present with one or more of the following symptoms: hemiplegia, persistent focal seizures, mental deterioration, and hemianopia. Mental deterioration is usually present to some degree but can be exacerbated by the persistent seizures. 3. Nursing implications include extensive preoperative teaching as to pathology, surgical procedure, and expected outcomes. Postoperative instruction involves training parents to assist their child with passive range of motion exercises or ambulation and the action and side effects of medications. PMID- 2315991 TI - Transfusion-associated Yersinia enterocolitica. PMID- 2315992 TI - The in vivo survival of human red cells with low oxygen affinity prepared by the osmotic pulse method of inositol hexaphosphate incorporation. AB - The purpose of this study was to determine the posttransfusion survival of low affinity red cells (RBCs) containing the hemoglobin modifier, inositol hexaphosphate (IHP). An osmotic pulse technique was used to incorporate IHP, a compound that normally does not cross the RBC membrane. Two groups of six volunteers were studied. RBCs were treated under conditions that resulted in a relatively large increase in mean corpuscular volume (delta MCV = 11.8 +/- 4.0, 1 SD) in Group I, but a relatively small increase (delta MCV = 5.5 +/- 1.9) in Group II. The groups had a similar decrease in mean corpuscular hemoglobin (delta MCH = -3.8 +/- 0.9 for Group I and -3.1 +/- 1.1 for Group II). The 24-hour posttransfusion RBC survival, measured with 3 mL of 51Cr-labeled autologous RBCs, correlated with the induced change in oxygen affinity, and larger shifts were associated with poorer survival. An acceptable 75-percent 24-hour posttransfusion survival was achieved for p50 increases up to approximately 15 torr. Cells that survived 24 hours appeared to have a normal lifespan. This study is the first demonstration of adequate survival for human RBCs with a potentially long-lasting decrease in oxygen affinity. PMID- 2315993 TI - Decreasing seroprevalence of human immunodeficiency virus type 1 in a regional blood donor population. AB - Blood banks have intensified their efforts to discourage donations from individuals at risk for the human immunodeficiency virus (HIV-1). Since the onset of HIV-1 donor screening in April 1985, a marked reduction in seroprevalence has been seen at the authors' institutions: from 51 cases per 100,000 donors in 1985 to 13 per 100,000 in the first 6 months of 1988. Data from 3.5 years have been analyzed for temporal trends in the association of HIV-1 seroprevalence with donation site (urban vs. non-urban) and donor gender. The association of HIV-1 seropositivity with an urban donation site decreased through 1987 as the urban-to nonurban donation odds ratio declined from 6.48 in 1985 to 2.54 in 1987. Despite this decrease, both men and women who donated in urban areas had a significantly higher seroprevalence than those in nonurban areas. Male donors had a higher overall HIV-1 seroprevalence than female donors. However, the male-to-female odds ratio declined from 2.94 in 1985 to 1.96 in 1988, and male gender was no longer significantly associated with HIV-1 seropositivity. This change in the donor profile appears to reflect declining numbers of seropositive men who acknowledge risk factors and greater numbers of women with no identified risks for HIV-1. This study documents a dramatic decrease in HIV-1-seropositive donors and suggests that the deferral of high-risk individuals has become increasingly successful. PMID- 2315995 TI - Identification of HIV-infected transfusion recipients: the utility of crossreferencing previous donor records with AIDS case reports. AB - An expanded "look-back" program has been developed, in which patients who may have been exposed to HIV through blood transfusion were identified via three triggers: the blood that they received was donated by persons who 1) have subsequently been reported to local health departments as meeting the diagnostic criteria for AIDS, 2) have donated since the introduction of anti-HIV screening and tested positive, or 3) have been found to be infected during investigation of reported transfusion-associated HIV infections. In comparing triggers, cross referencing the list of patients reported to have AIDS (AIDS case list) proved to be the most efficient approach for identifying HIV-infected donors and transfusion recipients. Of the 7973 AIDS patients reported in eight Northern California counties as of December 1988, 316 (4.0%) were determined to have donated at Irwin Memorial Blood Centers between 1977 and 1985. Despite the logarithmic increase in reported cases of AIDS in the San Francisco Bay area over the last 5 years, the rate of detection of previous donors from AIDS case lists remained between 3.3 and 5.4 percent. These persons accounted for 69 percent of the identified infected donors, and their identification led to notification of 60 percent of potentially exposed recipients and 51 percent of known infected recipients. The crossreferencing of AIDS case listings with blood bank records was equally efficient for regions with low and high AIDS prevalence. National adoption of AIDS case list crossreferencing is recommended as an effective means of identifying previously unidentified infected recipients in an effort to limit the secondary spread of HIV infection. PMID- 2315994 TI - Sepsis associated with transfusion of red cells contaminated with Yersinia enterocolitica. AB - Between April 1987 and May 1989, the Centers for Disease Control investigated seven cases of transfusion-associated Yersinia enterocolitica sepsis; four were caused by organisms of serotype O:3, and one each was caused by organisms of serotype O:1,2,3; O:5,27; and O:20. All seven recipients developed septic shock after receiving units of red cells (RBCs) contaminated with Y. enterocolitica; five recipients died. The cases occurred in seven states and were unrelated. There was no evidence for contamination of the RBC units during processing. Six of the seven donors had serologic evidence of recent Y. enterocolitica infection, and it is hypothesized that these donors had asymptomatic bacteremia when they donated the implicated blood. Four of the seven donors reported gastrointestinal illness in the 4 weeks before blood donation, and one donor became ill on the day he donated blood. Y. enterocolitica grows well at 4 degrees C and in the presence of dextrose and iron. If blood is contaminated at the time of collection, storage of the RBCs at 4 degrees C provides an ideal environment for bacterial growth and endotoxin production. These cases demonstrate the need for careful evaluation of patients with transfusion reactions for possible sepsis and suggest a need to screen prospective blood donors for mild gastrointestinal illness, including those illnesses not requiring physician evaluation or medication. PMID- 2315996 TI - Murine monoclonal antibody with anti-e-like specificity: suitability for screening for e-negative cells. AB - A directly agglutinating murine monoclonal antibody of the IgG3 isotype has been produced after mice were immunized with papain-treated Bombay phenotype, e positive red cells (RBCs). The antibody strongly agglutinated all e-positive RBCs and gave negative reactions with RBCs from Rhnull persons and those homozygous for Rh deletion genes. Variable reactivity was found with e-negative RBCs, ranging from weak to negative with R2R2, slightly stronger with r"r", and stronger still with RzRz. These reactions, together with results from tests with a large panel of Rh-variant RBCs, suggested a specificity for an epitope that is part of the e mosaic but is also expressed at least partially on e-negative RBCs and is influenced by the presence of C. This antibody has been standardized for use as a screening reagent for R2R2 cells by a microplate technique, and over 6000 donations have been screened in this way. No discrepancies have been found in confirmatory tests for e-negative status using human anti-e. PMID- 2315997 TI - Directed-donor programs may adversely affect autologous donor participation. AB - One hundred autologous whole blood donors (11 men, 89 women; 49 preoperative, 51 prenatal) completed a questionnaire concerning their motivations as autologous donors, their perceptions of the relative safety of blood donor options, and their interest in directed donations. Concern about acquiring AIDS from transfusion was the most prevalent reason for autologous donation. Nearly all participants knew that autologous blood was safer than volunteer blood, and most also believed that directed-donor blood was safer than volunteer blood. Most would have used a directed-donor program if available, particularly if they were ineligible as autologous donors. Furthermore, their interest in directed donations was unaffected by written material, provided pathway through the questionnaire, that included a statement that no scientific evidence exists to support directed donations' being safer than volunteer blood. One donor in five believed that autologous and directed donations were equivalent in safety, and 19 (15 of whom were prenatal donors) indicated that they probably or surely would not have participated in the autologous program if directed donations had been available. This study demonstrates that a sizable proportion of autologous donor candidates might not participate if a directed donation program were available. The unrestricted availability of directed donations may thus contribute to suboptimal use of autologous donor programs. PMID- 2315998 TI - Donation reactions among autologous donors. AB - Studies of risk factors associated with reactions among autologous blood donors have been limited. Therefore, 2091 autologous and 4737 homologous donations were examined. Donors at greatest risk for reaction were autologous donors who had reactions at first donation; among 45 who made repeat donations for the same surgery, 17 (38%) had repeat reactions. The group least likely to experience reactions were the autologous donors greater than or equal to 66 years old; they experienced a 1.9 greater than or equal to percent (6/310) incidence of reactions. More reactions were seen in both autologous and homologous donors in the categories of first-time donor, female gender, decreasing age, and lower weight. Multiple logistic regression analysis showed that all of these variables were independent predictors of donor reaction, with first-time donation (odds ratio, 2.4) and female gender (odds ratio, 1.9) being the strongest predictors of reaction. Donor room personnel should be alerted that autologous donors who react at first donation are very likely to react at subsequent donations. Contrary to common concern, elderly autologous donors are least likely to have reactions. PMID- 2315999 TI - Modification of fresh-frozen plasma transfusion practices through educational intervention. AB - The effect of an educational program designed to address misconceptions about the perioperative transfusion of fresh-frozen plasma (FFP) was examined. Results of a baseline audit of FFP use were compared to those of a study subsequent to the educational process. Statistical analysis of the data revealed that the decrease in the number of patients transfused with FFP, from 32 of 2077 operative cases in Group A (baseline) to 18 of 2540 operative cases in Group B (after education), was significant (p less than 0.01). Analysis of the justifications given for transfusion of FFP revealed that the increase in acceptable indications from 47 percent in Group A to 78 percent in Group B was also significant (p less than 0.05). There was no significant difference between the two groups in units of FFP transfused per patient (Group A, 3.66 +/- 3.2, vs. Group B, 2.47 +/- 1.7) or red cells (Group A, 2.84 +/- 5.2, vs. Group B, 5.22 +/- 4.4), and the patterns of platelet transfusion were similar in the two groups. There was a significant difference in the postoperative partial thromboplastin time (Group A, 38.2 +/- 8.7 vs. Group B, 56.3 +/- 24 seconds, p less than 0.01) but no significant difference in postoperative prothrombin time (Group A, 14.1 +/- 2.6 vs. Group B, 15.4 +/- 3.3 seconds). It can be concluded that an educational program designed to address misconceptions in transfusion practice can alter physician performance and thereby reduce the inappropriate use of FFP. PMID- 2316000 TI - In vivo red cell destruction by anti-Lu6. AB - An example is presented of an IgG1, anti-Lu6, that reacted by indirect antiglobulin test and was capable of destroying antigen-positive red cells in vivo. Two methods for the measurement of red cell survival, 51Cr labeling and flow cytometry, gave the same result: 20 percent of the test dose of Lu:6 red cells was destroyed in the first hour after injection and 80 percent in the first 24 hours. The clinical relevance of the antibody was correctly predicted by an in vitro monocyte monolayer assay. The finding that this example of anti-Lu6 was clinically significant should not be taken to mean that all antibodies directed against high-incidence Lutheran and Lutheran system-related antigens will behave similarly. When such antibodies are encountered, in vivo and/or in vitro studies to assess their clinical significance are necessary before rare blood is used for transfusion. PMID- 2316001 TI - Autoimmune hemolytic anemia caused by a cold agglutinin with a new specificity (anti-Ju). AB - A cold autoantibody detected in the serum of a patient with chronic idiopathic cold agglutinin disease and hemolytic anemia is described. The antibody reacted with adult as well as with cord red cells, and its reactivity was strongly diminished by treatment of the cells with neuraminidase and to a lesser degree by treatment with protease. Thus, the specificity of the antibody is distinct from those of all cold antibodies yet described. PMID- 2316002 TI - Cefotaxime-induced immune hemolytic anemia due to antibodies reacting in vitro by more than one mechanism. AB - Until recently, all cephalosporin-induced immune hemolytic anemias appeared to react by a "penicillin-type" drug adsorption mechanism, and hemolysis was extravascular. In 1987 and 1988, the first two cases of cephalosporin-induced immune hemolytic anemia with intravascular hemolysis associated with a so-called immune complex mechanism were reported. This report describes a case of extravascular hemolysis due to a third-generation cephalosporin, cefotaxime, which, to the authors' knowledge, is the first to show in vitro characteristics of both the drug adsorption and the so-called immune complex mechanisms. PMID- 2316003 TI - Inhibition of an anti-Pr1d cold agglutinin by citrate present in commercial red cell preservative solutions. AB - A patient with known cold autoimmune hemolyticanemia was admitted for surgery. Routine cold agglutinin evaluations, using commercial red cells (RBCs) in modified Alsever's preservative solution, revealed a cold agglutinin titer of 4 to 16. However, using RBCs washed four times with saline, a high-titer (greater than 2000 at 4 degrees C) cold autoagglutinin was demonstrated. The cold agglutinin was shown to be an IgM kappa paraprotein with anti-Pr1d specificity. The addition of Alsever's solution to washed RBCs inhibited the cold agglutinin. Each major component of Alsever's solution (neomycin, chloramphenicol, inosine, dextrose, and citrate) was tested individually; only citrate inhibited the patient's cold agglutinin. Various compounds structurally related to citrate were tested and found to cause various degrees of inhibition. The strongest inhibition correlated with the presence of either three carboxyl groups on molecules devoid of double-bonded carbon atoms or two carboxyl groups in cis configuration. A panel of 54 cold agglutinins, including 7 with anti-Pr specificity, was analyzed. None was significantly inhibited by Alsever's solution, although one with anti Pr2 specificity was weakly inhibited. In summary, these studies describe an anti Pr1d cold autoagglutinin that was inhibited by citrate in RBC preservative solutions. The failure to detect such a cold agglutinin can result from not washing RBCs free of citrate before testing. PMID- 2316005 TI - Abstracts of papers presented at the National Hemophilia Foundation's 41st annual meeting. October 10-14, 1989. PMID- 2316006 TI - Photopheresis: a therapy or an eclipse? PMID- 2316004 TI - Blood component therapy during the neonatal period: a national survey of red cell transfusion practice, 1985. AB - A questionnaire to determine patterns of neonatal red cell transfusion practice during 1985 was mailed to 2200 blood banks of American Association of Blood Banks (AABB) institutional members and children's hospitals. There were 915 responses (41.6%); 785 responses (86%) contained sufficient data for analysis. The majority (70.6%) of 785 responding hospitals were community/urban institutions. However, more highly specialized, pediatric hospitals were also represented by 92 university/tertiary-care hospitals (11.7% of respondents) and 29 children's hospitals (3.7% of respondents). Two-thirds of hospitals performed a major antiglobulin crossmatch (rather than an abbreviated one) before all neonatal red cell transfusions. The red cell preparation most frequently selected for small volume transfusions was ABO and Rh group-specific red cell concentrates. When performing only large-volume exchange transfusions, 19.2 percent of hospitals used whole blood; all others prepared reconstituted units of red cells plus fresh frozen plasma, a practice that frequently causes exposure to two donors per unit. Another practice likely leading to multiple donor exposure is the use of fresh frozen plasma to adjust the hematocrit of red cell preparations to a predetermined value prior to a small-volume transfusion. Over one-half of hospitals adjusting hematocrits used plasma, presumably from one donor, to dilute packed red cells from another donor, a practice that has no apparent medical benefit. Most hospitals (63.4%) provided red cells with a reduced risk of transmitting cytomegalovirus; blood from seronegative donors was selected by 65 percent of hospitals. The majority of hospitals, including most of the community/urban hospitals, did not irradiate blood products before transfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316007 TI - Preparation of white-cell poor platelet concentrates. PMID- 2316008 TI - Correct use of Scatchard plots. PMID- 2316009 TI - Prostanoid release in experimental liver transplantation. AB - Prostanoids are biologically active mediators of inflammation and tissue injury. To investigate the role of prostanoids in orthotopic liver transplantation we used a porcine model and determined prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 in arterial, portal, and hepatic venous blood during organ harvesting, the recipient operation, and the early postoperative period. There were no significantly increased serum levels during the donor operation or at the end of cold storage. As early as 1 or 5 min after initiation of reperfusion of the transplanted organ, prostanoids in hepatovenous blood increased dramatically (100-500-fold). Changes in arterial and portal blood (10 50-fold) were less pronounced but still statistically significant. In surviving animals these values returned to normal within 24 hr. The hepatic release of metabolites of the arachidonic acid cascade after liver grafting indicates that the synthesis of prostanoids might contribute to morphological and functional alterations of the transplanted graft. In addition, the increased arterial values of circulating prostanoids may potentially participate in severe cardiovascular, hemostatic, and immunological alterations known to occur after liver transplantation. PMID- 2316010 TI - The effect of renal ischemia on cyclosporine clearance in rabbits. AB - The renal handling of cyclosporine was studied in ischemically damaged kidneys in New Zealand White rabbits and nonischemic control animals. CsA, 25 mg/kg/day, was administered intravenously for 10 days starting with the day of operation. Blood CsA (B CsA) was higher in the ischemic group compared with the controls (median: 285 micrograms/L, range 95-785 micrograms/L vs. 170 micrograms/L, range 110-185 micrograms/L, P = 0.05) on day 1 after operation. B CsA dropped rapidly to a level equivalent to the controls by day 4 (median: 105 micrograms/L, range 60-280 micrograms/L vs. 195 micrograms/L, range 70-215 micrograms/L, P = NS). Median CsA clearance (C CsA) as a percentage of creatinine clearance (C Cr) was some ten fold greater in the ischemic animals (6.32%, range 2.93-18.41% vs. 0.55%, range 0.13-0.78%, P less than 0.001) on day 1. The ratio gradually declined, approaching the value in controls by day 10 (0.86%, range 0.24-7.21% vs. 0.23%, range 0.16-0.73%, P = 0.05). The data suggest that renal impairment has an important effect on CsA blood levels. In the clinical situation this may be of particular importance during both oliguria and the recovery from acute tubular necrosis. PMID- 2316011 TI - Incidence of skin cancer after renal transplantation in The Netherlands. AB - The incidence of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) was analyzed separately in all 764 patients who received a renal allograft between 1966 and 1988 at the Leiden University Hospital. The mean follow-up period was 8.7 posttransplant years (range 1-21 years). During this time period 176 skin cancers were diagnosed in 47 patients. The overall risk to develop a first tumor increased from 10% after 10 years to 40% after 20 years of graft survival. The overall incidence of SCC was 250 times higher and that of BCC 10 times higher when compared with the general Dutch population. Moreover the localization of SCCs and BCCs differed considerably. Solar radiation is thought to be an important risk factor for the development of skin cancer. However, the occurrence of skin cancer in long-term graft survivors forms also a major problem in a country with a higher geographical latitude and a moderate amount of sun exposure, such as the Netherlands. PMID- 2316012 TI - Characterization and significance of donor-reactive B cell antibodies in current sera of kidney transplant patients. AB - The specificity and class of antibodies resulting in a positive B cell crossmatch were studied in 47 kidney-transplanted patients. The study was performed to determine instances where a positive B cell crossmatch would not be deleterious to the survival of the graft. In order to determine the specificity and class of the antibodies, we used monoclonal antibodies to HLA-A,B,C and DR antigens to block cytotoxicity of sera, and the reagent DTT to characterize the immunoglobulin class. We found that graft survival in patients with DR antibodies was significantly better than in patients with class I antibodies (P less than 0.02). No difference in graft survival in patients with IgM antibodies versus patients with IgG antibodies was observed. The presence of weak HLA class I antibodies in patient's sera only detected as reactivity on B lymphoid cells should be considered a contraindication to transplantation. Thus our study shows that a fraction of patients who have cytotoxic B cell reactive antibodies at the time of transplantation can be successfully transplanted, provided the specificity of each serum is defined prior to transplantation. PMID- 2316013 TI - Outcome of patients with tuberous sclerosis after renal transplantation. AB - The fate of tuberous sclerosis (TS) patients after renal transplantation (RT) for end-stage renal failure remains to be defined. We report three patients with a posttransplantation follow-up averaging 54 months and review 6 previously published cases. Three women, aged 27-46 years, received a cadaver kidney 26-67 months after starting dialysis. None had mental retardation, 2 had suffered from seizures during infancy and 2 had intracranial calcification; neurological involvement was equally mild in the 6 reported patients. Currently, 16-84 months after RT, our 3 patients are fully rehabilitated with a well-functioning graft (serum creatinine 1.2-1.7 mg/dl). Results of RT are also satisfactory in the 4 other reported cases for whom a follow-up is available, except for 1 death unrelated to the initial disease. Neurologic disorders did not progress. Renal cell carcinoma was discovered in one removed kidney, and cells suggestive of malignant transformation in another case. No metastases were discovered up to 4 years later. No neoplastic transformation was observed up to 7 years after RT in the 3 patients who retained their native kidneys. TS patients with end-stage renal failure are good candidates for RT. The probably small risk of neoplastic transformation of native kidneys warrants a close monitoring by CT scan of the few patients who have not undergone bilateral nephrectomy. PMID- 2316014 TI - The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant recipients. AB - The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 (EPA) and 20% C22:6 omega-3 for three months on renal function variables was investigated in a placebo-controlled (6 g corn oil, 50% C18:2 omega-6) prospective, randomized, double-blind study in stable cyclosporine-treated renal transplant recipients, at least nine months after grafting. Ten patients ingested placebo capsules and eleven patients fish oil. When measuring glomerular filtration rate and effective renal plasma flow (ERPF) before (baseline [BL]) and after 3 months of oil ingestion nothing changed in the placebo-treated group: GFR BL = 64.5 GFR-3 months = 60 ml/min/1.73m2 (NS; median, Wilcoxon test) ERPF BL = 229.5 and ERPF-3 months = 242.5 ml/min/1.73m2 (NS). In the fish oil-treated group GFR rose by 20.3% from GFR-BL = 56 to GFR-3 months = 68 ml/min/1.73m2 and ERPF by 16.4% from ERPF-BL 218 to ERPF-3 months = 245 ml/min/1.73m2, (P less than 0.01). In the placebo-treated group mean arterial pressure and calculated total renal vascular resistance (TRVR) did not change: MAP-BL = 106 mmHg and MAP-3 months = 109 mmHg, TRVR being 20856 dyne.sec/cm5 and 19862 dyne/sec/cm5, respectively (NS). In the fish oil-treated group MAP and TRVR fell by 8.6% and 21.1%, respectively: MAP-BL = 106 mmHg and MAP-3 months = 98 mmHg (P less than 0.01), TRVR-BL = 21952 dyne/sec/cm5 and TRVR-3 months = 17087 dyne/sec/cm5 (P less than 0.01). According to these results fish oil supplementation has considerable effects on renal function and blood pressure in stable CsA-treated renal transplant recipients. PMID- 2316015 TI - Significance of arterial ketone body ratio measurement in human liver transplantation. AB - Arterial ketone body ratio (KBR), which reflects the NAD+/NADH ratio of hepatic mitochondria, was measured sequentially in 39 liver transplantations. In 22 cases, KBR was increased to above 0.7 within 6 hr after reperfusion (group A). In 11 cases, restoration of KBR was delayed until the first postoperative day (group B) and in 6 cases, KBR failed to recover (group C). The patients in group A survived liver transplantation without complications. By contrast, morbidity and mortality were significantly higher in groups B and C. In 2 cases in group C, the livers were clinically diagnosed as initially nonfunctioning grafts and the patients underwent retransplantation. Another two died of hepatic failure soon after the operation. It is suggested that delayed recovery of KBR is an early indicator of metabolic overload in the liver allograft, and that a delay exceeding 24 hr may imply the need for retransplantation. PMID- 2316016 TI - Hepatitis B liver disease in cyclosporine-treated renal allograft recipients. AB - To establish the impact of cyclosporine on the development of chronic hepatitis in hepatitis B surface antigen (HBsAg)-positive renal allograft recipients, the incidence and outcome of chronic hepatitis in 20 cyclosporine-treated patients (CsA group) were compared with 13 azathioprine-treated patients (AZA group). All 33 patients had a functioning graft for 2 years or longer. Twenty-nine of the 33 patients were HBsAg-positive prior to the initiation of hemodialysis. The difference in the incidence of chronic hepatitis between these 2 groups was not statistically significant (78.6% in the AZA group vs. 52.4% in the CsA group, P = 0.12). In the CsA group, 3 patients (15%) developed liver cirrhosis, and there was a 5% mortality. The AZA group had a 7.7% mortality, and 4 patients (30.8%) developed liver cirrhosis. Serial serum samples obtained from these 33 HBsAg positive renal allograft recipients were analyzed for antibody to hepatitis D virus (anti-HD). Anti-HD was found in 3 patients. Two of them developed anti-HD seroconversion after renal transplantation during a mean follow-up of 4 years. All 3 patients developed chronic hepatitis and 2 of them have subsequently developed liver cirrhosis. There was a mortality of 6.1% in 33 HBsAg-positive patients compared with a 5.3% mortality in 57 HBsAg-negative renal allograft recipients. The difference was not statistically significant. We conclude from this study that (1) CsA-treated HBsAg-positive renal allograft recipients have a tendency to develop chronic hepatitis like AZA-treated patients; (2) HBsAg positive patients have an increased risk of HDV superinfection after renal transplantation, and this may result in rapid progression to liver cirrhosis; (3) HBsAg-positive patients who acquire HBsAg prior to renal transplantation have a low overall mortality, including death due to liver disease, for a mean follow-up of 4 years. PMID- 2316017 TI - Intraoperative evaluation of EuroCollins and University of Wisconsin preservation solutions in patients undergoing hepatic transplantation. AB - The effects of cold liver preservation with two solutions, EuroCollins and University of Wisconsin, were compared in terms of hepatic function and hemodynamic parameters obtained intraoperatively during orthotopic liver transplantation. Data from 101 consecutive liver transplants were analyzed retrospectively, comparing 50 grafts preserved with EC with 51 preserved with UW solution. Hepatic hemodynamics parameters included portal venous and hepatic arterial flows, determined with an electromagnetic flowmeter. Vascular pressures, blood gases and pH measurements were obtained directly from the portal vein, hepatic vein, and peripheral artery. Serial measurements of serum glucose, SGOT, and SGPT were performed following reperfusion. Preservation related graft failure occurred in 4 of 50 patients in the EC group, but not in any of 51 patients in the UW group. Cold Ischemia time (hours +/- SEM) was significantly prolonged in UW group (7.23 +/- 1.4 vs. 5.21 +/- 0.9). Rate of temperature change (degrees C/hour +/- SEM) after reperfusion was similar in both groups (EC = 0.62 +/- 0.35, UW = 0.71 +/- 0.4). Peak serum SGOT, SGPT, and glucose levels following reperfusion were significantly higher in the EC group, as was PRBC and FFP administration. Systemic hemodynamics in both groups of patients were similar. However, UW-preserved grafts demonstrated a significantly higher hepatic artery resistance, with no other differences in hepatic hemodynamics seen. UW solution appears to extend cold ischemia time without adversely affecting liver function. However, the etiology and clinical significance of the increased hepatic artery resistance seen in UW-stored liver grafts are unknown. PMID- 2316018 TI - Augmentation of cell-mediated cytotoxicity following 50% partial hepatectomy. AB - The cytolytic responses of C3H/HeJ mice after 50% hepatectomy (PH) were assessed in a 4-hr 51Cr-release assay. Spleen cells (SC) (50 x 10(6] from normal or PH C3H/HeJ (H-2k) mice were sensitized with equal numbers of irradiated allogeneic DBA/2 (H-2d) spleen cells in a five-day mixed lymphocyte culture. Generated cytolytic activity was measured against 51Cr-labeled P815 mastocytoma (H-2d) and EL4 lymphoma (H-2b) target cells. The wet weight and cell numbers per spleen following 50% partial hepatectomy were 70% and 75% higher than the control values for the first 20 days, and then returned to normal levels by 21 days. The cytolysis by spleen cells from 2-, 14-, and 31-day PH mice were 89.3 +/- 0.7, 86.9 +/- 5.3, and 90.1 +/- 1.3%, respectively, compared with control (sham operated) values of 56.0 +/- 1.0, 57.0 +/- 2.0, and 49.9 +/- 7.0% (P less than 0.03 at E/T 100:1). This enhanced cytolysis by PH spleen cells remained high for at least 118 days after the liver resection before returning to control levels by 268 days. Cytolytic effector cells in PH SC were generated at least 24 hr earlier than in control SC. When normal and PH cytolysis were compared following primary and secondary in vitro sensitization, the cytolytic levels of primarily sensitized PH spleen cells were comparable to secondarily sensitized normal spleen cells. Furthermore, the primarily sensitized normal spleen cells did not show crossreactive cytolysis with EL4 target cells (H-2b), while both the primarily sensitized PH spleen cells and the secondarily sensitized normal spleen cells were significantly cross-reactive against the third party EL4 target cells. Adherent PH spleen cells appear to be responsible for this augmented cytolytic capacity since their coculture with normal nonadherent responder spleen cells increased control cytolysis by approximately 30%. These studied demonstrate that, following 50% partial hepatectomy, there is an immediate and sustained increase in the allospecific cytolytic response. PMID- 2316019 TI - Immunological unresponsiveness induced by ultraviolet-B-irradiated and nonirradiated skin grafts. AB - We previously reported that ultraviolet-B-irradiated B10.AQR tail skin grafts were permanently accepted by B10.T6R recipients in about half the cases. Such a beneficial effect on graft survival could only be demonstrated in this particular combination. We have now investigated whether these animals had become tolerant to the donor strain antigens. Nonirradiated B10.AQR tail skin grafted 50 days after acceptance of a UVB-irradiated B10.AQR graft was accepted in 9/9 cases, indicating that these animals had become tolerant to the B10.AQR alloantigens. However, secondary grafts on animals that had rejected the first graft also showed a prolonged or definite survival. This tolerance was specific; B10.T6R mice tolerant to B10.AQR grafts rejected B10 skin grafts, while F1(B10A X B10.AQR) and F1(B10 X B10A) grafts, sharing class II antigens with B10.AQR, had a slightly prolonged graft survival. Cells of tolerant animals showed normal proliferative responses against B10.AQR antigens. However, when autologous serum was added, proliferation was specifically suppressed. Likewise, this specific tolerance could be transferred with serum or serum and cells but not with cells only. Analysis of the sera of these animals showed long-lasting and donor specific high-titered cytotoxic antibody titers, which are likely to play a pivotal role in the observed suppression. PMID- 2316020 TI - A novel sulphate conjugate of cyclosporine occurring in high concentrations in vivo. AB - A novel, water-soluble metabolite of cyclosporine, a sulphate conjugate, present in high concentrations in human bile and plasma was evaluated for its immunosuppressive properties. The direct binding of the conjugate to surface molecules on lymphocytes was studied. The effect of the metabolite was tested in several in vitro systems, including MLR and mitogen-induced proliferation, Il-2 production, generation of CTL, and expression of surface antigens on lymphocytes after stimulation with mitogens. In vivo, the drugs were tested for suppression of the PFC response against SRBC. The results show an inhibitory effect of the conjugate in the generation of CTL and to some extent in the production of Il-2 but not in any of the other systems. The concentrations needed to achieve these effects exceeded those of CsA with a factor of 500-5000. PMID- 2316021 TI - Hemopoietic histocompatibility (Hh-1) regulatory and structural genes of the f haplotype map to H-2. AB - Natural resistance to bone marrow stem cell (BMC) grafts in lethally irradiated mice is a consequence of natural killer cell recognition and elimination of BMC that express hemopoietic histocompatibility (Hh) antigens inherited noncodominantly. The major Hh genetic region, Hh-1, maps to H-2. The phenotype of the BMC was determined by grafting BMC into panels of irradiated mice, and measuring splenic incorporation of the radioactive specific DNA precursor, 5-iodo 2'-deoxyuridine [125I] (IUdR) 5 days after cell transfer. Our previous analysis of Hh-1 antigen expression on BMC of intra-H-2 recombinant inbred strain mice indicated that Hh-1 regulatory genes (Hh-1r) map in the H-2S/H-2D interval. Nine recombinants described here shared the following: (1) the DL region was donated by H-2f that was associated with expression of determinant 2, shared with H-2d/Hh 1d, and (2) had crossovers in the S/D or Ea/S intervals or within Eb, and (3) had BMC that were Hh-1 null. F1 hybrids of crosses between mice of these recombinant strains with H-2d strain mice had BMC that expressed determinant 2, suggesting that a structural gene had been lost by the crossover event. Crosses with H-2b strain mice produced mice whose BMC were Hh-1 null, indicating that the H-2f/Hh 1f regulatory genes were still intact. We suggest that Hh-1r maps to the S/D interval of all haplotypes so far studied, even H-2f. The structural gene for the f haplotype is centromeric of Eb and may be Kf, based on recent data supporting the role of class I antigens in Hh antigen expression. PMID- 2316022 TI - Excellence of perfluorochemical with simple oxygen bubbling as a preservation medium for simple cold storage of canine pancreas. PMID- 2316023 TI - Postnecrotic cirrhosis following varicella hepatitis in a liver transplant patient. PMID- 2316024 TI - Sterility of bile in multiple-organ donors. PMID- 2316025 TI - Large airway inflammation in heart-lung transplant recipients--its significance and prognostic implications. PMID- 2316026 TI - Low-dose (one gray) total-lymphoid irradiation for extensive, drug-resistant chronic graft-versus-host disease. PMID- 2316027 TI - Peroperative appearance of serum class I antigen during liver transplantation. PMID- 2316028 TI - A new approach to the left-lateral segment hepatic transplant. The flop. PMID- 2316029 TI - Transplacental passage of cyclosporine after liver transplantation. PMID- 2316030 TI - More on life insurance for kidney donors. PMID- 2316032 TI - [Epidemiology of acute myocardial infarction]. PMID- 2316031 TI - Generic names need stereochemical information. Signs of support. PMID- 2316033 TI - [Heart transplantation in the era of cyclosporin]. AB - In a five-year period from February 1984, 76 orthotopic heart transplantations were performed in the most extensive heart transplantation programme in the Harvard Medical School in Boston, Massachusetts. The average age of the patients was 43 years (range 14-61 years) and the sex distribution was 55 men/21 women. Cardiomyopathy and ischaemic heart disease were the commonest indications for transplantation. The actuarical survival was 84% after one year, 81% after two years and 76% after five years. When the operative lethality is excluded, the one year survival was 91%, the two-year survival 88% and the five-year survival 82%. Six operative deaths occurred within the first 30 days and seven late deaths, five of these from acute rejection and two as a result of transplant atherosclerosis. No deaths were due to infection. Twelve patients developed 14 general surgical complications and laparotomy proved necessary in ten cases. One of the patients died from haemorrhagic pancreatitis and the remainder had no sequelae. An association was found between tissue type compatibility (human leukocyte antigen (HLA)) between donor and recipient and the occurrence of steroid resistant rejections. PMID- 2316034 TI - [The cryopathies]. AB - The term cryopathies includes conditions in which abnormal sensitivity to cold is a prominent feature and includes the cold agglutinin syndrome, the cold hemolysin syndrome, the cold urticarias, the cryoglobulinemias, and cryofibrinogenemia. The cryopathies may be secondary to lymphoproliferative, autoimmune, and infectious diseases, but in many patients no underlying disease can be found (essential cryopathy). Avoidance of cold is of prime importance in all patients. Underlying disease should be treated, if possible. Severe therapeutic problems may arise in patients with essential cryopathies. PMID- 2316035 TI - [Practical use of the brain death diagnosis]. AB - A retrospective review of a material spontaneous intracerebral haemorrhages and head injuries from a period of five years revealed that 14% of the patients with these diagnoses eventually are diagnosed as brain dead. In half of the brain dead patients cerebral angiography was carried out and, in all of the cases, this revealed circulatory arrest in the brain. The investigation demonstrates that, on the average, 8.5 hours elapse from the establishing of the diagnosis of brain death until cardiac arrest occurs. In 75 out of 105 cases, relations were asked for permission to remove organs and the reply was affirmative in 52 cases (69.3%). Two patients had already consented to organ donation. PMID- 2316036 TI - [Attitude to the criteria of death and kidney transplantation of the relatives of kidney donors]. AB - Fifty near relatives of cadaver kidney donors in the County of Ringkobing were questioned about how they experienced information concerning the brain death of the donor and the request for permission to remove the kidneys for transplantation. This was undertaken as an interview investigation. In addition, they were questioned as to whether they subsequently experienced doubt about the decision and about their attitude to the criteria for death. It was found that approximately half were aware of the seriousness of the condition before they were told by a doctor but that 35% would have desired more detailed information. Emphasis is placed, in addition, on improved conditions for a dignified parting from the decreased, not information by telephone and that the time for decision making was too short. The reasons for accepting removal of the kidneys were either knowledge of the donor's attitude or consideration of the recipient. Only three donors had drawn up donor testaments. Only one of the relatives regretted the decision while 20% had experienced doubts but the great majority would have liked to discuss the subject with others later. 63% accept the criteria for brain death and 14% the criteria for heart death but only 9% have altered their attitude as a result of the current debate. PMID- 2316037 TI - [A longitudinal study of the nutritional status of chronic dialysis patients]. AB - A longitudinal investigation was undertaken to follow the nutritional status of 30 patients receiving chronic dialysis (19 patients in haemodialysis and 11 patients receiving continuous outpatient peritoneal dialysis) over a period of 14 months. A significant decrease in serum transferrin from 28 mumols/litre to 25 mumols/litre was registered (Pratt's test 0.01 less than p less than 0.05) while three other nutritional parameters (Relative Body Weight (RBW), Triceps Skin Fold (TSF) and Mid-Arm Muscle Circumference (MAMC)) did not alter significantly. Employment of a nutritional scoring system revealed that the incidence and degree of malnutrition were unchanged during the period concerned. It is concluded that conventional dialysis therapy with a relatively liberal diet does not appear to result in improvement in the nutritional status of the dialysis patients and that prevention of malnutrition in patients with chronic renal insufficiency must receive high priority. PMID- 2316038 TI - [Julia Vldan's dietary plan for patients with lumps and cancer. An analysis and evaluation of the nutritional aspects]. AB - An analysis and assessment of the nutritional aspects of Julia Voldan's dietary regime for patients with lumps and cancer. The main constituents of the diet are raw, biodynamically cultured vegetables, particularly potatoes, root-vegetables and cabbage, raw milk and other milk products, raw eggs, nuts, seeds, peas, beans and herbal tea. Nutritional calculations revealed that the diet was adequate as regards energy, vitamins and minerals provided that the recommended large portions were eaten. 49% of the energy originated from fat, 12% from proteins and 39% from carbohydrates. Thus, a diet with a high fat content is concerned. The fat content is much higher than that normally recommended to ensure health and prevention of disease, including cancer. The raw milk constitutes a health risk and employment of great quantities of raw potatoes, raw root vegetables and cabbage make the diet voluminous and difficult for sick people with poor appetites to consume. This, together with the relatively low protein content increase the risk of development of incorrect nutrition or undernutrition. This diet may thus be responsible for unnecessary weakening of cancer patients. Recommending of Julia Voldan's dietary regime for patients with lumps and cancer is unsuitable from a nutritional point of view. PMID- 2316039 TI - [Assessment of the diet of malnourished outpatients with chronic obstructive respiratory insufficiency]. AB - We investigated the daily diets of malnourished patients with chronic obstructive ventilatory insufficiency. A total of 28 patients with body weights of less than 80% of ideal body weight were included. The patients were all ambulatory and in a stable phase of their illness. Their diets were assessed by dietary registration covering seven days. Basal energy expenditure was calculated using the Harris Benedict equation. On an average these patients had a daily energy intake of 205% of their total energy expenditure, which is significantly higher than the value of 150% of basal energy expenditure considered sufficient for normal daily activity (p less than 0.0001). We conclude that low energy intake is not the cause of low body weight in these patients. They seem to be in a hypermetabolic state which may be due to the increased energy demand of the exertion of breathing. PMID- 2316040 TI - [The risk of ornithosis among the staff of Copenhagen Zoo]. AB - Because a keeper in Copenhagen ZOO had developed ornithosis, clinical and serological examination of the staff of the ZOO was instituted. The object was to demonstrate any possible threatening epidemic and also to demonstrate if the staff of the ZOO were particularly exposed to the risk of ornithosis. Neither of these could be confirmed. PMID- 2316041 TI - [An EDP program for distribution of patients at a surgical department]. AB - A computer programme is described which can undertake automatic distribution of patients referred for elective surgery. The programme ensures coordinated reservation of operation and bed resources. The programme provides copies of admission and operation lists to the departments concerned and, similarly, it writes out distribution lists and summoning letters. The programme provides statistics for use in planning of resources and statistics with waiting lists according to diagnoses and the time of waiting. The programme is protected from illegal employment by unauthorized users as typing of the identity of the user and a personal code word are required. The programme fulfills the requirements to a register made by the supervision of registers concerning registers which contain very sensitive personal information. PMID- 2316042 TI - [Percutaneous transluminal coronary angioplasty in acute myocardial infarction]. AB - The attitude towards the treatment of acute myocardial infarction is currently changing. As an example of one of the new methods, a successful case of acute percutaneous transluminal coronary angioplasty is presented. Which of the new therapeutic regimens provides the best prognosis is unknown, but considering the resources and the hitherto published studies, intravenous thrombolysis seems in general to be the most advantageous, while the others ought only to be used on special indications. PMID- 2316043 TI - [Aorto-esophageal fistula]. AB - A case of aorto-oesophageal fistula is presented. The lesion was caused by rupture of a small saccular aortic aneurysm. PMID- 2316044 TI - [Atypical manifestation of extragonadal germinative tumors]. AB - Three cases of extragonadal germinative tumours, all with atypical manifestations are presented. All patients were treated as for germinative tumours and all of them were without any signs of recurrence 24 to 60 months after treatment. The literature is surveyed. It is concluded that although the histology of the tumour is uncertain, the location of the tumour and the tumour markers are atypical, younger patients where a germinative tumour cannot be excluded should be treated as for a gonadal germinative tumour with a cisplatinum-based combination chemotherapy. PMID- 2316045 TI - [The Danish Medical Statistics and Danish practical research]. PMID- 2316046 TI - [Diagnosis and evaluation of metabolic control in diabetes mellitus]. PMID- 2316047 TI - [Attempted suicide among children and adolescents--therapeutic possibilities within the health care]. PMID- 2316048 TI - [Ketanserin. A new antihypertensive agent with an antagonistic effect on serotonin]. PMID- 2316049 TI - [Patellar dislocation as a cause of osteochondral fracture of the femoro-patellar joint]. AB - Acute traumatic dislocation of the patella may be associated with osteochondral fractures. Clinical examination invariably shows a tense effusion. A detailed radiographic examination including antero-posterior, lateral and skyline views of the patella is usually necessary to establish an exact diagnosis. Once diagnosis is made open reduction and fixation of the osteochondral fracture should be carried out if it is possible. Out of 78 patients of our own with patella dislocation 24 cases suffered an osteochondral fracture. In ten cases refixation of the osteochondral fragment was achieved. Intraoperatively the alignment of the patella was controlled in any case. In cases of lateral subluxation lateral release and medial reconstruction was performed. In two cases medial transfer of the tibial tuberosity was carried out. Osteochondral fractures of the femoro patellar groove represent an important injury in the course of acute patellar dislocation. With exact diagnosis and correct treatment congruity of the femoro patellar joint can be restored in many cases. PMID- 2316050 TI - [Surgically stabilizing "complex therapy" of unstable injury of the lower cervical spine]. AB - Numerous assessments of the stability of screws within the cervical vertebral bodies after strong mechanical loading showed that spondylodesis can be considered as a stable fixation whether it is performed as a ventral, dorsal of combined procedure. Luxation fractures of the cervical spine, however, often do not only show lesions of the osteo-ligamentary structures, but are also accompanied by lesions of the spinal marrow. In addition to surgical measures, the self-destructing fermentative processes occurring in the mechanically injured spinal marrow have to be and can be eliminated or at least reduced by chemotherapy. The immediate simultaneous chemotherapeutic and surgical treatment is presented as "complex therapy" and recommended because of its good results. PMID- 2316051 TI - [Bicycle accidents--causes and sequelae. An evaluation of the 1986 calendar year]. AB - In a population of 402 motorcyclists and bicyclists, which were treated in the Traumatological Department of the University of Freiburg during 1986, we describe the different cause, spectrum and follow-up of the injuries. The special risk factors are discussed. The social implications show the importance of preventive measures to limit the risk of injury. With respect to the 70% of injured bicyclists with severe head injury, the wearing of safety helmets is strongly advocated. The effectiveness of cycle lanes is substantiated by our results. PMID- 2316052 TI - [Obturator dislocation of the hip joint]. AB - Luxatio obturatoria may occur in the case of a trauma affecting the hip joint when the latter is in a position of flexion, abduction and external rotation. The femoral head dislocates anteriorly and caudally towards the foramen obturatum. A recent case will be presented with a discussion of the general aspects of this injury, with special emphasis on concomitant injuries and their significance of the long-term prognosis. PMID- 2316053 TI - [Occupational accidents with possible HIV contamination]. AB - From January 1st, 1984 until December 31st, 1988 586 employees of the University Clinic of Frankfurt, West-Germany, were treated after occupational accidents with potentially HIV-contaminated materials. The majority of the patients were admitted because of lacerations that occurred with used injection needles. Up to now the sero-conversion of a patient after this special kind of trauma has not been documented in West-Germany. In our clinic we found an infection in one employee, which is due to an occupationally acquired injury. PMID- 2316054 TI - [Expert evaluation of children and students in legal accident insurance]. AB - Children and students take part in legal accident insurance as if they were adults. The functional impairment of the childish individual has to be measured. Therefore the child is treated as a fictious adult. The problem is explained by two examples. PMID- 2316055 TI - [Digital computer arthrometry of the upper ankle joint using a personal computer. A new procedure]. AB - The digital computerarthrometry (DCAM) was developed as a very cost-effective device to calculate the pathologic angles of injured joints. The joint's data are captured by a frame grabber-board installed in a personal computer after takeover from the X-rays by a video camera. Measurements are performed using a commercially available software package which displays the X-ray-photograph on a separate screen besides the one used to manipulate the computer. With this system the calculations of angles and distances of the injured joints are performed with considerably higher precision as it could be done before. As a further possibility bone density measurements may be done from the X-rays as it had been tried to before computers could be used. Our first results seem to present our system as an alternative to the costly workstations, that had to be used until now. PMID- 2316056 TI - [Adamantinoma of the fibula--follow-up study]. AB - A case of the adamantinom of the fibula has been reported. The tumor was resected six years ago. The yearly follow-up showed no sign of a relapse or metastases. PMID- 2316057 TI - [Management of subtrochanteric femoral fractures with the dynamic condylar screw]. AB - The 95-degree angled condylar screw (DCS) has been proven to be a valuable implant in the operative repair of comminuted and two-level fractures of the subtrochanteric region. Technically, it is easier to insert than the 95-degree angled condylar plate providing higher stability and the possibility of corrections even after insertion. PMID- 2316058 TI - Hormonal and cardiorespiratory changes following simulated saturation dives to 4 and 11 ATA. AB - Professional divers were compressed with trimix to 4 ATA (2 persons, aged 35 and 26) and to 11 ATA (3 persons, aged 34, 26, and 23) for saturation dives with durations of 48 and 50 h, followed by 33 and 109 h of decompression, respectively. Pre- and postdive cardiorespiratory reactions to a step test--heart rate (HR) and ventilation (VE)--and concentrations of growth hormone, corticotropin, cortisol, insulin, lutotropin, folitropin, triiodothyronine (T3), thyroxine (T4), thyrotropin, and testosterone in serum were studied. All divers developed postdecompression tachycardia (90-108 beats/min), which persisted 24 h after surfacing. Physical fitness assessed by steady state HR and VE during a step test was lowered 24 h after decompression compared with the predive values in 4 divers and enhanced in 1. These data provide evidence for hindered and delayed readaptation of the cardiorespiratory system to a normobaric environment. T3, T4, and testosterone were significantly decreased postdive. Hormonal responses were found to exhibit a very individual pattern from which it was possible to estimate the adaptive reactions after hyperbaric exposure. Professional divers with a lower level of physical fitness showed more pronounced hormonal responses to hyperbaric environments. PMID- 2316059 TI - Magnesium sulfate suppresses electroencephalographic manifestations of CNS oxygen toxicity. AB - We studied the effects of parenteral magnesium sulfate (MgSO4) administration on electroencephalographic seizures induced by hyperbaric oxygen (HBO) in awake rats. Sixteen rats chronically implanted with electrocorticographic electrodes were preinjected i.p. with either vehicle or 3 mmol/kg MgSO4 (the latter resulted in serum levels of 3.5-5.5 mmol/liter) and then exposed to 6 ATA O2 in a pressure chamber. The time to develop an electric ichtal seizure was measured and compared to that in the same animal receiving the alternate treatment 3 days later. Mean and median times after the magnesium treatment were almost double those of vehicle administration. A central anticonvulsive action of magnesium, which should be investigated over the entire HBO range, is indicated. PMID- 2316060 TI - Complement activation involvement in decompression sickness of rabbits. AB - A hypothesis has been proposed that claims much of the phenomena of decompression sickness (DCS) are mediated by the complement system of blood plasma. This "complement hypothesis" can be used to explain the variation in susceptibility of individuals to DCS, including the phenomena of acclimatization and de acclimatization. In this study, certain predictions of the complement hypothesis were examined by exposing rabbits to a particular pressure profile; some were observed to have symptoms of DCS and some showed none. Those that were observed to have symptoms were also found to have native complement systems that were activated by air bubbles, and those that did not show symptoms of DCS when exposed to the same pressure profile had native complement systems that were not activated by air bubbles. Rabbits that had shown symptoms of DCS the first 2 times that they were exposed to the pressure profile could be acclimatized to the pressure profile by pharmacologically decomplementing them in vivo. After being decomplemented, they showed no symptoms of DCS when they were exposed to the same pressure profile for a third time. When the decomplemented rabbits were allowed to remain inactive for a period of time that was sufficient to allow their complement systems to return to normal, after having been decomplemented, and were then subjected to the pressure profile for the fourth time, they were each again observed to have symptoms of DCS, i.e., they became de-acclimatized when their complement systems had returned to their native sensitivity. These results provide further experimental support for the complement hypothesis. PMID- 2316061 TI - [Prognostic value of HIV serum antigens]. AB - Human immunodeficiency virus (HIV) antigens can be detected during early infection but usually disappear afterwards. Their later reappearance in serum seems to herald a greater virus replication and a poor prognosis. The prognostic value of antigen detection at the first clinical visit was assessed among 37 symptomatic patients. Patients with detectable antigenemia at the first visit progressed more rapidly towards the acquired immunodeficiency syndrome (p less than 0.0001). Similarly, patients with detectable antigens at the time of a Pneumocystis carinii pneumonia had a shorter survival than patients without detectable antigens (p less than 0.0001). Four months after the hospital admission date, the survival rate was 31% among patients with detectable antigens and 100% among patients without detectable antigens (p less than 0.0001). In two of four patients tested, serial HIV antigens determinations suggested a spontaneous decrease of antigen titers during the terminal phase of the disease. PMID- 2316062 TI - [The antipneumococcal vaccine and elderly persons: not a luxury, a necessity]. PMID- 2316063 TI - [Sports injuries in elderly athletes. A 3-year prospective study, with controls]. PMID- 2316064 TI - [All that burns is not an ulcer]. PMID- 2316065 TI - The in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate and other parameters in human urine. AB - In this study, an efficient microtechnique (gel crystallization method) was used to investigate the in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate (Vcr) in human urine samples of 6 healthy volunteers. With a daily dose of 3 X 11 mmol of alkali citrate, Vcr decreased by 70%. This could have been due to the decrease of calcium excretion, which caused 50-60% of the total change, and to the increase of citrate and pH, each contributing about 20-25% to the decline of Vcr. The findings explain the clinical advantages of alkali citrates in the prevention of recurrent calcium oxalate stone formation. PMID- 2316066 TI - Effects of different doses of alkaline citrate on urine composition and crystallization of calcium oxalate. AB - Prophylactic treatment with alkaline citrate in patients with recurrent calcium oxalate (CaOx) stone disease results in reduced CaOx supersaturation and increased urinary citrate. The effects of a single evening dose were compared with those of two and three daily doses in six recurrent CaOx stone formers with hypercalciuria, hypocitraturia or raised calcium/citrate quotients. While on a standardized hospital diet the patients were given 7.5 g (28 mmol) of sodium potassium citrate (URALYT-U) in one, two, and three doses. Fractional urine collections during 24 hours were analyzed for pH, composition, and crystallization risk (CR). All dosage regimens had favourable effects on urinary calcium, citrate, calcium/citrate quotients, and CaOx-CR. The most sustained effect was recorded with three divided doses. Single evening doses resulted in the most pronounced effects between 22.00-06.00 h, thereby counteracting the increased risk of CaOx crystallization during that period. In terms of 24h urine composition the best effect was recorded with alkaline citrate administered three times daily, but because of the favourable response by a single evening dose between 22.00-06.00 h the assumption was made that this dosage regimen might be sufficient to reduce the risk of CaOx crystallization and stone formation. However, the validity of such an assumption can only be established by long-term clinical studies. PMID- 2316067 TI - Production of calcium oxalate monohydrate, dihydrate or trihydrate. A comparative study. AB - Procedures to obtain calcium oxalate monohydrate, dihydrate and trihydrate are presented and discussed. The influence of several additives and conditions in the formation of calcium oxalate dihydrate crystals are comparatively evaluated. It seems that the presence of colloidal phosphate favours the formation of calcium oxalate dihydrate crystals through heterogeneous nucleation. PMID- 2316068 TI - Glycose aminoglycane excretion and concentration in the urine of patients with frequently recurrent calcium-oxalate lithiasis prior to and following Diclofenac Na therapy. AB - Excretion and concentration of glycose aminoglycans were measured in 19 patients with frequent relapses of calcium-oxalate lithiasis, prior to and two weeks after onset of Diclofenac-Na therapy. In most patients, markedly enhanced glycose aminoglycan concentration and excretion could be demonstrated. Elevation of the high-molecular inhibitor potential in the urine results in reduced risk of calcium-oxalate lithogenesis, which may explain the therapeutic success of nonsteroidal anti-inflammatory drugs in the treatment of therapy resistant calcium-oxalate lithiasis. PMID- 2316069 TI - Determination of urinary oxalate by high-performance liquid chromatography monitoring with an ultraviolet detector. AB - High-performance liquid chromatography (HPLC) monitoring with an ultraviolet detector was carried out to measure urinary oxalate levels in urolithiasis. Interfering substances in urine were removed by anion exchange prior to chromatography. This procedure was found excellent with respect to sensitivity, reproducibility, and analytical recovery. The findings were in agreement with colorimetric date. The mean oxalate level in 24-hour urine was 30.5 +/- 15.1 mg in patients with a single episode and 36.3 +/- 9.8 mg in recurrent stone formers. The latter values was significantly higher than the normal control level (27.4 +/ 3.8 mg). PMID- 2316070 TI - Sialic acid concentrations in the urine of men with and without renal stones. AB - It has been suggested that urinary sialidase may play a role in the formation of renal stones. The present study was therefore undertaken to compare spectrophotometrically the different types of sialic acid concentrations and sialidase activities in fresh first morning urine specimens of men (21-65 years) with (13) and without (9) calcium oxalate renal stones. Although the free urinary sialic acid concentrations of the two groups of men were statistically about the same (P = 0.0614), the total (P = 0.003) and bound (P = 0.0012) urinary sialic acid concentrations differed significantly. Both the total and bound sialic acid concentrations were lower in the urine specimens of the stone patients than in their healthy counterparts. This decrease in urinary sialic acid concentrations was firstly thought to be the result of elevated breakdown enzymes of sialic acid, which would favour the production of pyruvate. However, spectrophotometric determinations of the endogenous pyruvate concentrations of the two types of urine specimens did not differ significantly (P = 0.0708). Secondly, the decrease in total urinary total sialic acid concentration of stone patients, could be attributed to less sialic acid synthesis or less renal excretion. Therefore, the same experiments were repeated using serum of 13 patients and 9 healthy men. Conversely, the total (P = 0.4425) and bound (P = 0.2850) serum sialic acid concentrations were found to be similar in the two types of subjects. However, the free serum sialic acid concentration of stone patients was significantly lower than in the healthy subjects (P = 0.0062).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316071 TI - The effects of fractioned human urine on urease-induced crystallisation in vitro. AB - Previous studies have shown human urine to have an inhibitory action on urease induced crystallisation. Centrifugation and 0.45 microns filtration of the urine did not reduce this activity. This eliminates larger urine particles as being the cause of the inhibitory activity. Both the retenate and the filtrate after ultrafiltration of urine with a 100.000 mol weight cut-off influenced the urease induced crystallisation of magnesium ammonium phosphate and calcium phosphate. The results indicate that the inhibitory action is exerted by more than one urinary component. PMID- 2316073 TI - Side-effects of extracorporeal piezoelectric shock wave lithotripsy (EPL). AB - In the Department of Urology, University of Freiburg, West Germany extracorporeal piezoelectric shock wave lithotripsy (EPL) has been used in the treatment of urinary and biliary stones since November 1987. The first 85 treatments (in 71 patients) for renal stones were evaluated with regard to complications and side effects. There was no need for any anesthesia. Urinary obstruction was observed in 12% of the cases. Aside from the urinary obstruction and urosepsis (2%) no serious complications were seen. Endourological auxiliary measures were applied in 32% (27% prophylactically). The temporary glomerular damage which appeared in some patients vanished within 6 days after treatment. Because of possible asymptomatic ureteral obstruction a close follow up by ultrasound is recommended. EPL was found to be a useful method of treatment for renal calculi with few side effects. PMID- 2316072 TI - Blood cellular and biochemical changes after extracorporeal shock wave lithotripsy. AB - The present study deals with blood cell behaviour and related hematochemical changes occurring in man after exposure to extracorporeal shock wave lithotripsy (ESWL). The following parameters have been investigated, before and after treatment, in a longitudinal study carried out on 58 patients of our Center: RBC count, Ht, Blood Hb, Plasma Hb, autohemolysis after 72 hours, bilirubinemia, WBC count, platelet count, in vitro platelet aggregation, beta-TG, sideremia and urinary post-exposure transferrin concentration. After exposure to ESWL, with pulse numbers ranging from 350 to 3,000, 18-20 KV, direct and indirect evidences of hemolysis have been found when number of SW exceeded 1,000. The hemolysis rate in different models of in vitro exposure to ESWL of blood samples was also investigated. Increase of WBC count, and changes of the platelet in vitro aggregation patterns were also observed. Changes in sideremia values have been related to urinary loss of transferrin. PMID- 2316074 TI - "Dry lithotripsy" by a simple modification of the Chinese lithotripter KDE-1. AB - We report on the improved technique upon a water bath lithotripter. With a simple water balloon device added to the Chinese KDE-1 Type water bath lithotripter, an extracorporeal shock wave dry lithotripter has been developed. From June to December 1988, there were 300 cases of upper urinary tract calculi and gallbladder stone treated with this machine with excellent results and no severe complications. The improved technique would be made reference to change old water bath machines into dry (water balloon) machines. PMID- 2316075 TI - Second European Symposium on Stone Disease. March 22-24, 1990, Basel, Switzerland. Abstracts. PMID- 2316076 TI - Hydration feature of urinary compounds. Evidence for molecular abnormality in calcium oxalate urolithiasis. AB - Proton-relaxation-time measurements were performed on lyophilized urine samples collected from 11 recurrent calcium oxalate stone-formers, 9 uric acid stone formers, 9 patients with various urological disorders, and 20 normal individuals. The T1 and T2 relaxation times were determined using a Bruker PC Multispec at 20 MHz at 37 degrees C for measurements of lyophilized sample and thereafter during gradual controlled rehydration. The prolongation of the relaxation times as a function of rehydration was found to differ significantly (P less than 0.005) between, on the one hand, the calcium oxalate stone-formers and, on the other hand the normal, uric-acid stone-formers, and patients with other urological disorders. Water compartmentalization was then calculated according to the fast proton diffusion model. At most of the experimental points during rehydration process, significantly (P less than 0.001) less water was bound to the compounds of urine from calcium oxalate stone-formers than that obtained from normal individuals. The variations in the bound hydration water may have been associated with possible changes in the structure or configuration of the compounds present in the urine of the different groups. The results reflect differences in the urinary content and/or properties of normal subjects and calcium oxalate stone formers, and indicate that the mechanism of bound water relaxation is in some way specific to the pathophysiological state of urine. PMID- 2316077 TI - [Electronic data processing-assisted text processing at the clinic and in general practice]. AB - Word processing is currently the most frequent application for personal computers, and a wide variety of standard software is available. The capabilities of modern word-processing software includes the convenient typing and correction of all routine correspondence, as well as the professional layout of scientific manuscripts. The decision to purchase a certain word-processing programm should be made according to local needs and prerequisities. Three to six months may be necessary to fully adapt the organization of a clinic or private practice to the new technology. PMID- 2316078 TI - [NAG (N-acetyl-beta-D-glucosaminidase)--a sensitive marker for disorders of kidney function]. AB - In a clinical study we tested the use of the lysosomal enzyme NAG as a parameter of kidney function. Following prospective randomization, we examined NAG excretion during cisplatin treatment with/without nephroprotection, after intravenous urography with ionic/non-ionic contrast media, during lower/upper urinary tract infections and before/after extracorporeal shockwave lithotripsy for intrarenal calculi (first-generation equipment used). Measurements were performed in 3-h urine specimens and in urine collected over 24 h, using a simple method of analysis. A correlation between NAG leakage and functional disorder of the renal tubular cells seemed likely on the basis of additional clinical and experimental data. Increases, in some cases dramatic, in NAG excretion were observed after the administration of cisplatin and ionic contrast media, in acute pyelonephritis, and after extracorporeal shockwave lithotripsy. However, the increase in NAG excretion was less impressive during cisplatin therapy when nephroprotective amino acids were infused, and in the urography group when non ionic contrast media were used. Infections of the lower urinary tract did not increase NAG excretion. The results indicate that NAG is a sensitive marker of occult renal dysfunction, which can be checked by non-invasive techniques and can be used in a clinic setting to detect functional disorders of the kidney. PMID- 2316079 TI - [Clinical value of new rapid nuclear magnetic resonance tomography in preoperative assessment of hypernephroma. A prospective comparative study of CT and MR]. AB - The new technique of rapid magnetic resonance imaging (MRI) with a paramagnetic contrast agent provides excellent imaging of the kidneys and their lesions. MR imaging of this anatomical region at short breath holding intervals matches the well-known quality of computed tomography (CT) for the first time. MR and CT studies were performed on 36 patients with proven renal cell carcinoma. Different investigators evaluated the staging of the tumor by means of both techniques in a prospective study. In all patients a radical nephrectomy was performed. Surgical and pathological findings were compared. Though little difference was found in diagnostic value between the two systems, MRI results concerning the T-stage were better. Venous invasion was clearly shown by MRI without the use of contrast medium. Furthermore, sagittal and transaxial images provided a more direct assessment of the extent of the tumor and its demarcation to healthy parenchyma. Thus, MRI is helpful in planning of the surgical approach when organ-sparing excision of renal tumors is to be performed. PMID- 2316080 TI - [Adjuvant systemic interferon alpha-2B treatment in treatment refractory anogenital Condylomata acuminata]. AB - Despite different treatment modalities, resistance to treatment is observed in 4 15% of patients with anogenital condylomata acuminata. A total of 16 patients with resistant condylomata acuminata or extended infection affecting an area of more than 6 cm2 were treated with a prospectively defined therapy entailing laser treatment and adjuvant systemic interferon-alpha 2B (3 x 1 MU/day for 7 days). Of the 16 patients, 13 (81%) were in complete remission after an 8-month period of follow up. The typical side-effects of interferon were attenuated in 80% of cases by simultaneous paracetamol (3 x 500 mg/day). The combination of laser treatment and adjuvant systemic interferon-alpha 2B seems to be highly effective in the treatment of resistant or extended condylomata acuminata. At present, these results are being tested for significance in a prospectively randomized study. PMID- 2316081 TI - [Differentiation of human sperm cells using flow cytometry]. AB - An improved method for differential staining and high-resolution flow cytometric measurement of human sperm cells is presented. Involving a mild pretreatment with citric acid/detergent and staining with DAPI, the new procedure provides excellent preservation and good discrimination of all cells present in normal and pathologic semen samples. PMID- 2316082 TI - [How do I avoid being accused of malpractice? Or: the "ten commandments"]. PMID- 2316083 TI - Hyperbilirubinemia after single-stage radical cystectomy and ileal loop diversion. AB - One hundred ninety-two patients underwent single-stage radical cystectomy and ileal loop diversion over a three-year period. Postoperative hyperbilirubinemia occurred in 21 patients (10.9%) within the first ten days. Early hyperbilirubinemia occurred in 11 patients by postoperative day 5, accounting for 52 percent of the hyperbilirubinemic patients and 5.7 percent of the study population. Elevation persisted into the six to ten-day postoperative period for 9 at which time a total of 18 patients had bilirubin levels elevated above their presurgical values (P less than 0.001). This clinical observation appears to be benign and worthy of further investigation. PMID- 2316084 TI - Artificial urinary sphincter cuff erosion. Experience with reimplantation in 38 patients. AB - Artificial urinary sphincter cuff erosion has become rare but remains a dreaded consequence of sphincter implantation. Our experience indicates that with rational and systematic management of this problem, sphincter reimplantation can restore continence in many of these patients. During a ten-year period, 412 artificial sphincters were implanted at the Mayo Clinic. Bladder neck or urethral erosion occurred in 64 patients (15.5%). Ultimately, 38 patients had reimplantation, and the outcome was successful in 32 (84%). After the advent of delayed activation, the incidence of cuff erosion decreased greatly--from a peak of 18 percent (12 of 66 cases) in 1977 to 1.3 percent (1 of 79 cases) in 1985. PMID- 2316085 TI - Intraoperative and early complications of staging pelvic lymph node dissection in prostatic adenocarcinoma. AB - Pelvic lymphadenectomy is the final staging procedure before institution of therapy for patients with clinically locally confined adenocarcinoma of the prostate, a normal acid phosphatase, and a bone scan free of metastatic disease. The pathologic information it provides cannot be accurately acquired at the present time by any other method. Extraperitoneal lymphadenectomy is associated with some morbidity intraoperatively and in the early postoperative period. We enumerate our results with 284 extraperitoneal lymphadenectomies. PMID- 2316086 TI - Five-year survival following excision of renal cell carcinoma extending into inferior vena cava. AB - Fifteen consecutive patients having radical nephrectomy and excision of tumor extension from the inferior vena cava for pathologic Stage 3A renal cell carcinoma were followed up for a minimum of five years. Survival was compared with patients having radical nephrectomy for Stage 2 or Stage 3 renal cell carcinoma in the same time interval. Five-year survival in the Stage 3A group (47%) was similar to that for patients with Stage 2 tumors (54%) and significantly better than Stage 3 patients with positive lymph nodes at surgery (12%). Renal cell carcinoma with venous extension has a reasonable prognosis after surgical excision and warrants an aggressive surgical approach. PMID- 2316087 TI - Cystourethrograms characteristic of bladder instability in children. AB - Cystourethrograms characteristic of bladder instability are illustrated. A repeated increase of intravesical pressure causes functional and morphologic deformities of vesicourethral configuration: ballooning of the proximal urethra, ureteric reflux, and trabeculated bladder during the storage phase; and dilatation of bladder neck and proximal urethra, and a pearl string-like configuration of urethra during the voiding phase. The clinical significance of these observations is presented. PMID- 2316088 TI - A true hermaphrodite with some unusual features. AB - A fifteen-month-old boy with ambiguous external genitalia was found to have a 46XX karyotype, an ovotestis in the right labioscrotal fold, and an absent left gonad. He also had a rudimentary uterus and fallopian tubes and a blind-ending vagina lined with squamous epithelium. These features are compared with those more commonly found in true hermaphroditism. PMID- 2316089 TI - Ureteroscopic stone manipulation during pregnancy. AB - We report on 2 successful cases of ureteroscopic stone manipulation during pregnancy using the rigid ureteroscope. These 2 cases are reported to show the utility of this technique when applied to low ureteral stones presenting in third trimester of pregnancy. We believe this technique is safe, both for the mother and the fetus, when carefully applied to selected individuals. PMID- 2316090 TI - Dose response relationship of methotrexate in combination with cisplatin in murine bladder cancer. AB - Methotrexate (MTX) has activity in transitional cell carcinoma (TCC) in man and some have suggested an advantage of high-dose methotrexate versus the standard dose in controlling tumor growth and prolonging survival. MBT-2, a poorly differentiated TCC induced by the carcinogen FANFT, is both grossly and histologically similar to human TCC and has been used as an animal model. One hundred twenty C3H/HE female mice were injected in the hind limb with 7.5 X 10(4) MBT-2 tumor cells. When palpable tumors developed in all animals, therapy was initiated. Animals were randomized into a control group and nine treatment groups as follows: cisplatin (DDP), MTX32 mg, MTX50 mg, MTX80 mg, DDP + MTX32, MTX50 + Leucovorin, MTX80 + Leucovorin, DDP + MTX50 + Leucovorin, DDP + MTX80 + Leucovorin. The combination of MTX50 mg with Leucovorin + DDP and DDP alone were the two most effective regimens in controlling tumor growth and prolonging survival. No statistically significant difference was observed between the group treated by high-dose MTX alone and those treated by low-dose MTX. No toxicity was observed even when high doses of MTX were used. PMID- 2316091 TI - Diphallus with third urethra. AB - An unusual case is reported of a fifteen-year-old adolescent boy, who was born with two independent phalli. Both organs featured separate, completely developed urethras, including an extra urethral remnant in the right penis. A third hypospadic perineal urethral duct equipped with a mechanical sphincter also could be identified histologically. Bilateral simultaneous erections could be achieved easily. A review of published cases suggests that this may be the first example of a complete diphallia coexisting with a third urethra. PMID- 2316092 TI - Percutaneous suprapubic cystostomy using balloon dilation. PMID- 2316093 TI - Injectable internal ureteral stent. PMID- 2316094 TI - Analysis of voiding disorders in patients with cerebrovascular accidents. AB - Urodynamic evaluation was undertaken in 33 patients (15 males and 18 females, age range 48-90 years) with voiding problems following cerebrovascular accidents. In the majority of these patients (26) cystometry revealed involuntary contractions of the bladder. The critical volume for involuntary bladder contractions was approximately 200 mL. The majority of patients with cerebral cortex and/or internal capsule lesions had uninhibited relaxation of the sphincter during involuntary bladder contractions, while all of the patients with lesions only in the basal ganglia or thalamus had normal sphincter function. The remaining 7 patients had poor bladder contractions. Correlation of bladder dysfunction with the area of brain injury was not conclusive, but was suggestive of directions to be taken in future research. PMID- 2316095 TI - Pseudotumor of left kidney due to sarcoidosis. AB - Presence of granulomas in the kidney have been reported in up to 40 percent of patients with sarcoidosis. However, granulomatous infiltration producing renal enlargement with distortion of the normal renal contour, and mimicking renal "pseudotumor" is exceedingly rare and is the subject of this case report. Radiographic, scintigraphic, and histologic findings are presented. PMID- 2316096 TI - Extra-adrenal pheochromocytoma causing renal artery stenosis and implications of magnetic resonance imaging as diagnostic tool. AB - Extra-adrenal pheochromocytoma causing renal artery stenosis is very uncommon. We describe a patient who had hypertension from this entity. Surgical excision of the mass corrected the renal artery stenosis without the need for bypass grafting, and the patient has remained normotensive. Magnetic resonance imaging (MRI) showed an extremely bright lesion on T2 weighted image, which is virtually pathognomonic. MRI is the most sensitive modality for the detection of an extra adrenal or unsuspected multiple pheochromocytoma. This should obviate the need for routine abdominal exploration in the evaluation and treatment of pheochromocytoma. Therefore we strongly recommend magnetic resonance imaging in the management of adrenal masses in general and pheochromocytomas in particular. PMID- 2316097 TI - [Economic yields of life insurance]. PMID- 2316098 TI - [Changes in the benefits spectrum of medical insurance by the development of advanced technology medicine]. AB - The development of technical, diagnostic and therapeutical treatment in medicine to high-tech medicine and the survival of patients with necessity of permanent medical treatment and the development of a disadvantageous age structure of the population will need a continuous going up of costs in health maintenance. Restrictive handling of unnecessary medical treatment can only for a short time delay the going up costs, but it cannot stop this development or reverse it. PMID- 2316099 TI - [Medical malpractice in relation to its social political importance]. AB - Despite an unchanged legal basis the number of proceedings concerning medical practitioner's liability has increased substantially and medical law has developed into an independent field of law in the last 20 years. On one hand this is a result of modern medicine's extended possibilities to act and control, on the other hand it is caused by the patient's changed attitude towards both, his disease and his physician. Hereby the mass media exercise considerable influence with their commentaries, that are often exaggerated in their criticism and their representation. But this development gives no rise to concern. The jurisdiction in the field of medical practitioner's liability is--apart from a few exceptions- not overstated but necessary for the safeguarding of the patient's interests. It doesn't impede progress, doesn't give cause for a defensive medicine and doesn't burden our public health system. For the patient's wellbeing it often even accomplishes the important function of convincing the public health administration, that sometimes shows a tendency to act economically, of strict medical demands. There still is no room for the general conclusion, that the control of medicine by jurisdiction has undermined the confidential relationship between patient and physician. The recently published result of an opinion poll has shown, that physicians still enjoy a high reputation, while journalists--in spite of some contradictory statements--find themselves in the last ranks. PMID- 2316100 TI - [Dialysis and kidney transplantation]. AB - In the Federal Republic of Germany more than 22,000 patients receive renal replacement therapy. More than 6000 patients live with a functioning graft. Thus the Federal Republic of Germany holds leading position of internationally high standard. Since 1969 the non profit-organisation KfH major contributions to secure dialysis treatment; since 1976 KfH was engaged in the organisation of kidney transplantation. Future goals are the strengthening of reliable and secure dialysis facilities as well as--at least--2400 kidney transplantations per year in the FRG. This figure represents the approximate number of new uremic patients to be treated each year. PMID- 2316101 TI - [Health resorts--dissatisfaction with health resorts]. AB - An efficient medical rehabilitation is an important part of a modern health care system. There should be no doubts about its necessity. The medical rehabilitative system in Germany however, as it is organized by the sick-insurances and the annuity-insurances, does not fulfil all the claims urgently required. Much criticism seems really correct: the missing scientific basis of rehabilitation, the poor flexibility around the administrative procedures of application and performance, which is inadequate to medical needs, the nearly total absence of any negative selective criteria on the one hand and the huge problems in finding out those persons badly needing rehabilitative measures on the other, and last not least the uncertainty regarding the real economic benefits of the total enterprise of rehabilitation as it is actually practised. PMID- 2316102 TI - [Drug research and insurance medicine]. AB - The inflation in hospital financing has fallen off. The new regulations brought in with the health reform law (Gesundheitsreformgesetz) could help to cut hospital running costs and lead to a more economical form of medical treatment. At present a prognosis of these cost reductions is not possible. The new list of charges for medical treatment (Bundespflegesatzverordnung) brought in by the government in 1986 also has helped in reducing expenditure. Especially the requirement for self-budgeting and performance-costing has lead to a reduced inflation rate in medical treatment costs. An effective control of medical treatment costs demands more management not only in administrative but also in medical areas as well. Improving hospital economy must not automatically lead to a reduction in the quality of the service provided. PMID- 2316103 TI - [Therapy costs at the hospital]. AB - The inflation in hospital financing has fallen off. The new regulations brought in with the health reform law (Gesundheitsreformgesetz) could help to cut hospital running costs and lead to a more economical form of medical treatment. At present a prognosis of these cost reductions is not possible. The new list of charges for medical treatment (Bundespflegesatzverordnung) brought in by the government in 1986 also has helped in reducing expenditures. Especially the requirement for self-budgeting and performance-costing has lead to a reduced inflation rate in medical treatment costs. An effective control of medical treatment costs demands more management not only in administrative but also in medical areas as well. Improving hospital economy must not automatically lead to a reduction in the quality of the service provided. PMID- 2316104 TI - [The 1985/87 mortality table]. AB - The life-table is a mathematical model. On the base of probabilities of death the life-table gives statements about the expectation of life for each age. It also shows how many persons will--on an average--reach a certain age. Since 1871/81 the life expectancy for newborn children has doubled. 1871/81 only 74.7% of all male new-born children finished the first year, to-day this share is more than 99%. During this time the number of male persons that reached an age of 80 years increased from 5% to 37%. PMID- 2316105 TI - [A personal computer assessment program for increased risk in life insurance]. AB - The computer aided underwriting procedure means a substantial progress compared to the classical method. It enables less skilled people to rate substandard risks within specific limits. All important data will be saved automatically and can be retrieved for statistical or other analysis. PMID- 2316106 TI - [Equilibrium function in patients with chronic encephalopathy as an indicator of compensation level in cerebral circulation insufficiency]. AB - The equilibrium function of 52 patients suffering from chronic hypertensive encephalopathy was examined using a stabilographic method combined with provocative tests. It was found that their static and dynamic equilibrium declined when compared to that of healthy subjects of matched age. Dynamic equilibrium varied to the greatest extent, especially their capacity of responding adequately to strong stimuli, whereas static equilibrium changed in a far lesser degree. Comparison of the functional stability of the equilibrium system and the compensation level of cerebral circulation lesions revealed significant (p less than 0.01) changes in patients with varying degree of compensation. This observation suggests that the factor of functional stability can be used to measure the level of compensation of cerebral circulation lesions. PMID- 2316107 TI - [Particularities of hearing disorders in inhabitants of Mali]. AB - Audiologic examinations of the Mali people showed that neurosensory hypoacusis was the most common hearing problem, the incidence of which tended to increase. Altogether 147 patients (or 294 ears), aged 10 to 60 years, were examined, the duration of their hearing impairment varying from 1 month to 20 years. In terms of the pathological causes, all the patients were divided into 3 groups: 1) ototoxic antibiotics and quinine, 2) cerebrospinal meningitis, and 3) infectious disease. The patients underwent tonal threshold, suprathreshold and speech audiometry and showed impairment of primarily peripheral type. The prevalence of this type of pathology is indirect evidence that in this country the incidence of vascular pathologies is low and that prophylaxis of infectious diseases is necessary. PMID- 2316108 TI - [Treatment of secretory otitis media]. AB - Blood serum of 38 patients with otitis media (14 men and 24 women), aged 16 to 55 years, was examined immunologically. The patients were subdivided into two groups that received identical traditional therapy. However the Group 2 patients were also given per os 0.5 g sodium nucleinate 3 times a day for 10 days. Before and after treatment all the patients underwent immunological tests which included measurements of T- and B-lymphocytes, T-helpers and T-suppressors as well as immunoglobulins M, A, G and complement. It was demonstrated that sodium nucleinate exerted beneficial clinical and immunological effects. PMID- 2316109 TI - [Indicators of the state of hearing and olfactory analyzers in healthy man]. AB - This paper presents the concept of a biological norm, methods of experimental studies, and parameters of the hearing and olfactory function as derived from large-scale examinations of healthy people of different sex and age groups. On this basis parameters of the physiological norm for the hearing and olfactory function were calculated as applied to various age groups. The paper gives tables of average thresholds and limits of variations of hearing and olfactory sensitivity adapted for practical use. The tabulated data can be employed to evaluate examination results, to make early diagnosis, and to assess performance capabilities in the norm and pathology. PMID- 2316110 TI - [Characteristics of otorhinolaryngologic diseases in the indigenous rural population of the North]. AB - This paper presents the data describing specific features of ENT diseases in the aboriginal population of the North (Yakutians) obtained through mass-scale detailed examinations of the villagers. ENT pathologies were identified in 52.7% of those taken under examination. Among the pathologies ear diseases were in the first place (43.8%), pharyngeal diseases were in the second place (38.2%), nasal and paranasal diseases in the third place (14.2%). It is concluded that the prevalence and structure of ENT diseases among the population of the Far North should be taken into consideration when organizing ENT medical assistance in this area. PMID- 2316111 TI - [Specific features of otorhinolaryngologic diseases in patients with hemophilia]. AB - The fact that ENT doctors infrequently diagnose hemophilia is explained by their inadequate knowledge of the disease. We examined 35 patients suffering from hemophilia A and 3 patients suffering from hemophilia B. The most frequent ENT pathology in them was relapsing nasal hemorrhages of varying intensity and duration (20 patients). Chronic tonsillitis was identified in 17 hemophiliacs. In 2 patients, angina was aggravated by hemorrhages from the tonsils and life threatening hemorrhages to the soft tissues of the pharynx, neck and mediastinum which led to airways stenosis. In 3 patients, adenoids of the I degree and in 5 patients, adenoids of the II degree were detected. Among other ENT pathologies mention should be made of deformed nasal septum (13 cases), chronic otitis media (4 cases) and chronic suppurative mesotympanitis (1 case). In summary, the most common ENT disease in hemophiliacs is pathology of the lymphadenoid pharyngeal ring detected in more than half of the patients examined. Taking into consideration the specific and life-threatening pattern of potential complications of this pathology, it is important to choose efficient therapeutic methods. PMID- 2316112 TI - [Specific features of the clinical course and treatment of chronic tonsillitis in children]. AB - This author applied present-day methods--clinical, immunological, immunomorphological--to examine 2262 children with chronic tonsillitis and processed the data obtained statistically. The emergence and development of chronic tonsillitis were strongly stimulated by preceding cases of angina, acute respiratory pathologies, flu, and other infectious diseases. The children were treated using dioxidine, desensitizing drugs, vitamins, ultrasonic and tubus quartz exposures as well as levamisole. The treatment was effective and caused no complications. PMID- 2316113 TI - [Clinical aspects of otogenic abscesses of cerebral hemispheres]. PMID- 2316115 TI - [Microcirculation of the nasal mucosa in persons of the older age groups]. AB - Specific features of microcirculation of the mucous membrane of the nasal cavity of 32 patients over 57 years were investigated. Additionally, microcirculation of the mucous membrane of the nasal septum and wall of untreated rabbits and rabbits, that for 5 months were on a cholesterol enriched diet, was examined. It was shown that in both cases the transport function of capillaries and, consequently, the structure of the mucous membrane deteriorated which may contribute to the development of persistent rhinosinusitis. PMID- 2316114 TI - [Magnetic resonance tomography in the diagnosis of paranasal sinusitis]. AB - The potentialities of a new method--magnetic resonance tomography (MRT)--as applied to the diagnosis of paranasal sinusitis are discussed. The method permits detection of inflammation in the paranasal sinuses identified as a significant enhancement of a signal in the projection of the affected sinus. This paper presents two cases: patients with rhinosinusogenic cerebral arachnoiditis and arachnoencephalitis in whom paranasal pathologies which had no clinical manifestations were diagnosed by MRT. This helped to choose adequate therapy. In contrast to X-ray methods, MRT causes no unnecessary irradiation which allows repeated examinations. PMID- 2316116 TI - [Morphological changes in the nasal mucosa after diathermo-coagulation in chronic hypertrophic rhinitis]. AB - Morphological changes were investigated in 15 patients suffering from chronic hypertrophic rhinitis after 1, 3, 7, 14, 21, 30, and 120 days of treatment with high frequency current diathermocoagulation of concha nasalis. During treatment an area of coagulation necrosis was formed along the electrode passage which was replaced with sclerotic connective tissue by day 30. The tissue provided a stable reduction of the hypertrophic concha nasalis. The functional activity of its mucous membrane remained unaltered. PMID- 2316117 TI - [The Northern variant of the norm in the thermal picture of the face]. AB - One hundred and ten healthy residents of the cities of Krasnoyarsk and Norilsk were examined using the method of thermal visualization. As a result, a symptomcomplex of the thermal face picture typical of the Northern version of the norm was detected and described. When compared to the controls from Krasnoyarsk, delta T of the target group from Norilsk was on the average 0.07 degrees C lower. The knowledge of the thermal normogram in the Far North can help adequately interpret face thermograms of patients with nasal and paranasal pathologies in different geographical regions. PMID- 2316118 TI - [Surgical treatment of patients with cancer of the larynx with lesions of the anterior commissure]. AB - Eighty two patients with glottic tumors extending to the anterior commissure underwent surgical treatment: 11 patients for cordectomy in its classic form, 11 patients for fronto-lateral cordectomy, 59 patients for extended cordectomy, and 1 patient for hemilaryngectomy according to Otan. Analysis of the postoperative clinical state of the patients suggests that surgery for vocal cord carcinoma involving the anterior commissure should not necessarily include tracheostomy and laryngeal tamponade. PMID- 2316119 TI - [Local immunologic manifestations in chronic hyperplastic laryngitis. 1. Epithelial-stromal interactions in the mucous membrane of the "intact" larynx (morphometric analysis of dissected samples)]. AB - Local immunological manifestations of chronic hyperplastic laryngitis were investigated on the basis of quantitative determination of epithelial-stromal interactions in the mucous membrane of the larynx of subjects having no respiratory problems. Autopsy examinations (histotopograms) showed that lymphoid cells were nonuniformly distributed in the laryngeal mucous membrane: the pattern of distribution depended on the type of epithelium and its integrity, state of the basal membrane, stroma collagen content and vascularization. The distribution can be viewed as a characteristic of the adaptive potential of the laryngeal mucosa. PMID- 2316120 TI - [Cochleovestibular syndrome caused by sphenoiditis]. AB - Due to sphenoiditis, the patient developed a cochleovestibular syndrome at the labyrinthine level which was eliminated only by surgical treatment of sphenoiditis. This observation suggests that sphenoiditis can be referred to the factors responsible for hearing and vestibular disorders. Another interesting observation was that in the presence of pus in the sphenoidal sinus contrast X ray did not reveal a filling defect. Such a finding was not the first of this type seen by the author. PMID- 2316121 TI - [Certain aspects of otorhinolaryngologic care in Moscow's polyclinics]. PMID- 2316122 TI - [A case of a symptomless course in rhinogenic meningitis]. PMID- 2316123 TI - [Abscess of the left auricular, zygomatic and occipital regions of a tuberculous etiology on the background of bilateral chronic suppurative mesotympanitis]. PMID- 2316124 TI - [Chronic suppurative polypous maxillary sinusitis caused by a retained tooth]. PMID- 2316125 TI - [Ultrasonic surgery in multiple osteomas of the paranasal sinuses]. PMID- 2316126 TI - [Otogenic abscess of the occipital lobe]. PMID- 2316128 TI - [Congenital aneurysm of the internal carotid artery with a clinical course of a peritonsillar and retropharyngeal abscess]. PMID- 2316127 TI - [Multiple rhinogenic intracranial complications with favorable outcome]. PMID- 2316129 TI - [Characteristics of motion sickness during prolonged otolith stimulation in anti orthostatic position]. AB - Thirty healthy volunteers were tested for an extended period of time (up to 4 hours) on modified parallel swings during a head-down tilt (-8 degrees) study. The pattern of motion sickness that developed in this situation was evaluated in terms of physiological parameters (electrocardiography, rheoencephalography, arterial pressure, respiration rate electrooculography, etc.), hormonal status, fluid-electrolyte balance, sensory function. The test subjects developed a vestibulo-hemodynamic syndrome that included vestibular disorders, spatial illusions, fluid displacement in the cranial direction, excitation of the hypothalamic-pituitary-adrenal system, changes in fluid-electrolyte balance. The resulting data may help better understand mechanisms underlying motion sickness. PMID- 2316130 TI - [Profuse auricular hemorrhage caused by lesion of the sigmoid sinus associated with arterio-sinus anastomosis]. PMID- 2316131 TI - [Modification of the horizontal resection of the larynx with preservation of the free part of the epiglottis]. PMID- 2316132 TI - [Portable rhinomanometer for studying the function of nasal respiration]. PMID- 2316133 TI - Toxicology of selected pesticides, drugs, and chemicals. PMID- 2316134 TI - A connective tissue defect in two rabbits similar to the Ehlers-Danlos syndrome. AB - A connective tissue disease resembling the human Ehlers-Danlos syndrome is reported in two sibling rabbits about four months old. The clinical signs included skin hyperextensibility and fragility and poor wound healing. There were ultrastructural abnormalities in the structure of the collagen fibrils and in their arrangement in bundles of fibres. Affected rabbits may be a useful laboratory animal model for collagen disorders in human beings. PMID- 2316136 TI - Food safety. PMID- 2316135 TI - Enzootic abortion of ewes. PMID- 2316137 TI - Acute cardiomyopathy in heifers. PMID- 2316138 TI - Oestrus control in the ferret. PMID- 2316140 TI - Public health, food hygiene and OVS work. PMID- 2316139 TI - 'Magic mushroom' poisoning in a dog. PMID- 2316142 TI - Animal rights. PMID- 2316141 TI - Vaginal probes. PMID- 2316143 TI - Blood tests for FIP. PMID- 2316144 TI - Caesarean sections on BSE cows. PMID- 2316145 TI - Report emphasises links between human and animal disease. PMID- 2316146 TI - International disease surveillance. Quarterly report October to December 1989. PMID- 2316147 TI - Disease conditions diagnosed in culled adult cattle sent to an abattoir either with or without a veterinary certificate. AB - Lesions were detected in 208 culled cattle examined at a slaughterhouse. Eighty two of them had a veterinary certificate, and 30 of these had been slaughtered on the farm. The principal diagnoses included lameness (88 cases), mastitis (35), chronic infections (32), complications of parturition (20) and fractures and dislocation (14). Most of the 126 animals sent for slaughter by farmers without a veterinary certificate were suffering from lameness (71), mastitis (29) or chronic infections (18). Over 90 per cent of the animals with complications of parturition or traumatic injury had a veterinary certificate. The carcases of 33 (26 per cent) of the animals sent for slaughter without a veterinary certificate were rejected by the meat inspector, and 29 (35 per cent) of those with a veterinary certificate were rejected; the difference was not statistically significant. PMID- 2316148 TI - Testing strains of Clostridium perfringens type A isolated from diarrhoeic piglets for the presence of the enterotoxin gene. AB - A diarrhoeic syndrome in piglets has been linked to Clostridium perfringens type A because this organism has been isolated in large numbers from all cases. The strains isolated from these cases and strains isolated from healthy piglets were screened for the enterotoxin gene of C perfringens by DNA-hybridisation. Using two different synthetic DNA-probes, none of the strains isolated from diseased pigs was positive in this reaction, indicating that the enterotoxin of C perfringens is not involved in the syndrome. PMID- 2316149 TI - Comparison of cobalt supplemented anthelmintics and injected vitamin B12 for cobalt-deficient lambs. PMID- 2316150 TI - Neospora caninum encephalomyelitis in a British dog. PMID- 2316151 TI - Eosinophilic rumenitis in intensively reared lambs. PMID- 2316152 TI - Intellectual needs of practice. PMID- 2316153 TI - Digital dermatitis control. PMID- 2316154 TI - Detection of Salmonella. PMID- 2316155 TI - Diuresis following medetomidine. PMID- 2316156 TI - Working party on AI and embryo transfer. PMID- 2316157 TI - Changes to structure of welfare supervision proposed by FAWC. PMID- 2316158 TI - Cyromazine pour-on for the prevention of cutaneous myiasis of sheep. AB - The results of trials on eight farms to assess the efficacy of two pour-on formulations containing cyromazine for the prevention of cutaneous myiasis of sheep are presented; data from trials on sheep with larval implants and on sheep kept in cages with adult flies are also reported. The incidence of cutaneous myiasis was reduced by between 87 per cent and 100 per cent for eight weeks when a formulation containing 6 per cent w/v cyromazine was used at an application rate of 60 to 85 mg of active ingredient/kg bodyweight. When a formulation containing 10 per cent w/v was used at an application rate of 50 to 100 mg/kg, the incidence of the condition was reduced by between 90 per cent and 100 per cent for eight weeks. Studies of sheep with larval implants, using the formulation containing 10 per cent w/v cyromazine at 50, 100 and 150 mg/kg bodyweight gave variable results with some animals at each dose rate having lost protection by the seventh week. When sheep were treated with the formulation containing 10 per cent w/v cyromazine at 50 or 100 mg/kg and exposed to adult flies in fly-proof cages they were completely protected for nine and eight weeks, respectively. PMID- 2316159 TI - Tonic immobility in spent hens after catching and transport. AB - Tonic immobility tests were used to obtain information about the levels of fear in end-of-lay hens after they had been transported to four commercial processing plants. They stayed in a condition of tonic immobility longer than hens which had only been caught and removed from cages. There was no evidence that they became habituated to transport during journeys of up to five hours, but there were significant differences between the levels of fear expressed by birds transported by the different processors. PMID- 2316160 TI - The efficacy of triclabendazole and other anthelmintics against Fasciola hepatica in controlled studies in cattle. AB - In eight controlled tests 274 cattle were used to assess the efficacies of triclabendazole, albendazole, clorsulon, nitroxynil, oxyclozanide and rafoxanide against Fasciola hepatica. Against one-, two- and four-week-old early immature fluke the mean efficacies of triclabendazole given orally at 12 mg/kg were 88.1, 95.3 and 90.7 per cent, respectively. Clorsulon, nitroxynil and rafoxanide administered at recommended dose rates showed negligible activity against these stages of the parasite. Against six- and eight-week-old infections the mean efficacies of triclabendazole at 12 mg/kg were 87.5 per cent and 95.7 per cent, respectively. Against F hepatica aged six weeks, albendazole and oxyclozanide showed no activity and clorsulon, nitroxynil and rafoxanide had only slight to moderate activity. The efficacies of triclabendazole, clorsulon, nitroxynil and rafoxanide against 10- or 12-week-old parasites were 100, 99.0, 99.1 and 90.1 per cent, respectively. Albendazole and oxyclozanide showed poor efficacy against 12 week-old infections. PMID- 2316161 TI - An outbreak of botulism in captive hamadryas baboons (Papio hamadryas). PMID- 2316162 TI - Generalised progressive retinal atrophy in the English setter in Norway. PMID- 2316163 TI - Guidance for veterinary surgeons handling BSE cases. PMID- 2316164 TI - BSE, scrapie and laboratory models. PMID- 2316165 TI - Public health. PMID- 2316166 TI - Tail docking. PMID- 2316167 TI - Welfare standards in the EC. PMID- 2316168 TI - Complementary medicine. PMID- 2316169 TI - Blood tests for FIP. PMID- 2316170 TI - Calculation of body surface area from bodyweight. PMID- 2316171 TI - Evaluation of acid-base disturbances. PMID- 2316172 TI - Aujeszky's disease in foxhounds. PMID- 2316173 TI - Presence of microfilaria parasites in the red neck lizard. PMID- 2316174 TI - Preliminary trials using a macrocyclic lactone against psoroptic scabies of cattle. AB - A macrocyclic lactone, LL-F28249 alpha, C36H52O8, was evaluated as a one- or two injection treatment in different formulations and concentrations against cattle infested with Psoroptes ovis (Hering). One injection of 2 mg kg-1 or two injections of 1 mg kg-1 of 3% active material in either an aqueous or oil formulation failed to eliminate all of the mites. A single injection of 3 mg kg-1 as a 5% aqueous formulation eliminated all mites for 35 days post-injection. At lower dosages of the aqueous formulation (3%), the male mites appeared to be less susceptible to the acaricide than either the female or immature mites. PMID- 2316175 TI - Haemorrhagic pancarditis in cattle infected with Trypanosoma vivax. AB - Haemorrhagic pancarditis has been studied microscopically and ultrastructurally. Haemorrhages, oedema, mononuclear cell infiltration, degeneration, fragmentation, atrophy and lysis of myofibres, and extravascular localisation of the parasite were observed. PMID- 2316176 TI - The relationships among ecto- and endoparasite levels, class I antigens of the bovine major histocompatibility system, immunoglobulin E levels and weight gain. AB - Natural infestations of the cattle tick Boophilus microplus, levels of the buffalo fly Haematobia irritants exigua and faecal nematode egg concentrations (Bunostomum phlebotomum, Cooperia spp., Haemonchus placei, Oesophagostomum radiatum and Trichostrongylus axei) were assessed in 221 Belmont Red calves during the post-weaning period, when the animals were between 9 and 18 months of age. In addition, the 98 males of this group were challenged with B. microplus larvae on two separate occasions. There were strong positive correlations among replicate assessments of the same parasite. Field tick counts and tick counts following deliberate challenge were strongly correlated, and both showed negative correlations with post-weaning weight gain. There was a weak positive correlation between buffalo fly counts and post-weaning weight gain. There was a negative correlation between total worm egg count and weight gain. Among worm species, only the effect of O. radiatum on weight gain was significant. Cattle with bovine major histocompatibility (BoLA) antigens W6.1 and W7 had significantly fewer ticks than cattle lacking these antigens. Cattle with BoLA antigens W7 and CA36 had lower concentrations of nematode eggs in their faeces than cattle lacking these BoLA antigens. PMID- 2316177 TI - Appetite, digestive efficiency, feed utilization and carcass evaluation of housed calves naturally infected with gastrointestinal nematodes. AB - The progress of two groups of 10 calves, which had previously been exposed to trichostrongyle infections by grazing infected pastures, was monitored from housing in October to slaughter the following April. Each of the animals of one group had received a morantel sustained release bolus, the other control group remained untreated. The high faecal egg counts and serum pepsinogen concentrations, together with the clinical signs of ostertagiosis observed in the controls in October, persisted during the first month of housing but improved thereafter. From late November onwards, no difference in feed intake and digestive efficiency was observed between the groups. The control calves exhibited a significantly greater feed conversion efficiency over the period February-April, (7.5 vs. 12.3 kg feed kg-1 liveweight gain, P less than 0.001). This reduced the liveweight advantage of the MSRB group over the controls at housing to 25 kg. PMID- 2316178 TI - A drug incubation infectivity test (DIIT) for assessing resistance in trypanosomes. AB - Blood stream forms of drug-resistant and sensitive Trypanosoma brucei brucei, Trypanosoma brucei evansi and Trypanosoma vivax were incubated in a liquid medium for 24 h at 37 degrees C in the presence of various concentrations of diminazene aceturate (Berenil) or isometamidium chloride (Samorin), and assayed for infectivity in mice. Whereas the infectivity to mice of all Samorin-sensitive trypanosomes was decreased after incubation with 1 ng Samorin ml-1, the Samorin resistant stocks remained infective for mice. Two of the Samorin-resistant stocks remained infective after incubation with Samorin concentrations of up to 50 ng ml 1. The infectivity of Berenil-resistant trypanosome stocks were also retained after incubation with drug concentrations (0.5 or 1.0 micrograms ml-1) which otherwise inhibited the infectivity of Berenil-sensitive trypanosome stocks. In addition, differences in infectivity were observed when Berenil-resistant and sensitive trypanosome stocks were incubated in medium supplemented with serum from goats previously treated with Berenil. Thus, drug-resistant and sensitive trypanosomes can be clearly distinguished using the drug incubation infectivity test. PMID- 2316179 TI - The dispersion of the Karoo paralysis tick, Ixodes rubicundus, within a naturally infested population of sheep in South Africa. AB - The ratio of variance to mean (s2/means) of numbers of Ixodes rubicundus (males and females) per sheep was used as a measure of the dispersion pattern of this tick within a naturally infested population of sheep. Sheep were divided into two groups, one with previous contact with I. rubicundus and the other with no previous contact. Samples of 10 sheep from each group were searched for ticks on a weekly basis for 19 weeks during the winter of 1986. In each group, both male and female ticks had an s2/means ratio greater than 1 for the majority of observation periods indicating an aggregated dispersion pattern. The degree of aggregation was greater with increasing density of the ticks. The implications of these results are discussed both in relation to sampling procedures and potential control strategies. PMID- 2316180 TI - Immunization of pigs with culture antigens of Taenia solium. AB - An evaluation has been made of the protective effect of immunizing pigs with excretory-secretory homologous antigens on Taenia solium infections. This procedure reduced the number of cysticerci established from a challenge infection. PMID- 2316181 TI - Prevalence of Toxoplasma gondii infection in man and animals in Guangdong, Peoples Republic of China. AB - Tissue and serum samples from animals and man in Guangdong Province of the Peoples Republic of China were examined for Toxoplasma gondii infection. Tissues from 519 swine, 576 rodents, 84 people, one cat and two dogs were bioassayed in mice. T. gondii was isolated from 13 pools of swine tissues, but not from any other hosts. Serum samples from animals and man were examined at 1:64 dilution in the indirect hemagglutination test. Antibodies to T. gondii were found in 10.4% of 816 pigs, 0.9% of 955 rodents, 0.7% of 3085 people, 4.4% of 90 cattle, 8.3% of 12 rabbits and 2.1% of 47 cats. None were found in 83 buffaloes. PMID- 2316182 TI - Observations on the pathogenicity for sheep and goats and the transmissibility of the strain of virus isolated during the rinderpest outbreak in Sri Lanka in 1987. AB - The pathogenicity for sheep and goats of the virus strain that caused acute rinderpest in cattle and domestic buffalo in Sri Lanka after an interval of over 40 years has been examined. The results show that it can cause overt clinical disease in goats, but only mild or unapparent infection in sheep. The disease was transmitted from infected sheep to in-contact susceptible sheep and calves. PMID- 2316183 TI - The effect of Mycoplasma bovis on fertilization processes in vitro with bull spermatozoa and zona-free hamster oocytes. AB - The effect of Mycoplasma bovis (Donetta strain) on the ability of bull spermatozoa to interact with zona pellucida-free hamster oocytes was studied in an in vitro assay. Ejaculates of semen from a fertile Holstein bull were used fresh on the day of collection (unextended semen) as well as diluted with egg yolk-citrate and used the following day (extended semen). The addition of M. bovis to both unextended and extended semen at a mycoplasma to sperm cell ratio of 10:1 significantly reduced sperm penetration rates and the mean number of sperm per penetrated egg. Similarly, the ability of spermatozoa to form pronuclei and the activation of penetrated oocytes were adversely affected by M. bovis. No apparent effect on sperm motility was detected. When M. bovis was added to the oocytes, there was a marked reduction in the sperm penetration rates and fertilization processes suggesting that the organism affects certain oocyte function(s). The results indicate that the presence of M. bovis in semen or in the female reproductive tract may affect fertilization. Moreover, the in vitro assay with hamster oocytes was found to be useful for demonstrating the effects of contaminating microbial agents on bovine fertilization processes. PMID- 2316184 TI - Surface parasitism of the fish mycoplasma Mycoplasma mobile 163 K on tracheal epithelial cells. AB - The interaction of Mycoplasma mobile 163 K with epithelial cells was investigated in tracheal organ cultures of gnotobiotic rats by electron microscopy. Ultrathin sections showed that the epithelial cells were heavily colonized and damaged by the mycoplasmas 2 days after infection. Numerous organisms were attached to fragments of the cytoplasmic membranes; others entered the injured cells and adhered to cell structures. Organisms were interconnected by fibrillary material supporting their adherence to the cell surface. Non-infected tracheal rings remained viable, differentiated and well organized up to 28 days of cultivation. The present investigation characterizes M. mobile 163 K as a surface parasite. PMID- 2316185 TI - Mitogen stimulation of canine normal and myasthenia gravis lymphocytes. AB - Responses of canine lymphoid tissues to mitogens were studied in five normal dogs and in two dogs with acquired myasthenia gravis (MG). In the normal dogs, lymph node-derived lymphocytes gave the most consistent proliferative responses to concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM), as determined by thymidine incorporation; and in most cases PHA, lipopolysaccharide (LPS), and PWM stimulated total IgG production, as determined by ELISA. Splenic lymphocytes had the greatest capacity for increased total IgG production. In the myasthenic dogs total IgG production by unstimulated lymph-node-derived lymphocytes was 88 micrograms/ml and 153 micrograms/ml, much higher than that of unstimulated normal dog lymphocytes (mean less than 1.0 microgram/ml). All mitogens resulted in suppression rather than stimulation of IgG production by lymphocytes from dogs with MG. Production of antibodies to acetylcholine receptors (AChRs) was detected in the supernatants of lymphocyte cultures from one of the dogs with MG at a rate of 78 fmol/5 x 10(5) cells per week and was not detected in culture supernatants of control dogs. This study demonstrates that lymph nodes may be an important site of antibody production in myasthenic dogs and provides the necessary groundwork for future studies of the cellular immunology of canine MG. PMID- 2316186 TI - Phagocytic functions of pulmonary alveolar macrophages in genetically selected lean and obese swine and the effects of exogenous linolenic acid upon cell function. AB - Alveolar macrophages from genetically selected obese and lean swine were compared for in vitro phagocytic capabilities, using Fc (gamma)- and C3-mediated phagocytosis. Cells from obese pigs were significantly more effective at Fc (gamma)-mediated phagocytosis than those from lean pigs, both for percentage of total cells phagocytosing (P less than 0.044) and for the average number of opsonized sheep erythrocytes (SRBC) ingested per phagocyte (P less than 0.045). A seasonal interaction was noted for average number of SRBC ingested per phagocyte: the relative difference in macrophage responses between obese and lean groups became significantly more pronounced during winter and spring months (P less than 0.080). Macrophages from obese pigs also exhibited higher phagocytic activities at C3-mediated phagocytosis than did cells from lean pigs, but these differences were significant only for average number of SRBC ingested per phagocyte (P less than 0.080). Exogenous linolenic acid was added to selected cultures undergoing Fc (gamma)-mediated phagocytosis. Addition of the fatty acid frequently caused enhanced phagocytosis. Macrophages from obese pigs were stimulated by fatty acid treatment more frequently than cells from lean pigs (P less than 0.05). Relatively greater enhancement was also seen in cells from obese pigs, when compared with those from lean swine (P less than 0.025). These results suggest that genetically transferred factors are of primary importance in alveolar macrophage phagocytic responses and that linolenic acid can induce increased phagocytic activity by porcine alveolar macrophages in vitro. PMID- 2316187 TI - Modulation of canine lymphocyte blastogenesis via histamine. AB - The effect of histamine on in vitro T cell blastogenic responses of canine peripheral blood lymphocytes to phytohemagglutinin-P (PHA-P) was investigated. A dose dependent inhibition of blastogenesis was observed; an effect which could be blocked by cimetidine, a type II histamine receptor antagonist, but not by diphenhydramine, a type I receptor antagonist, suggesting that histamine's inhibitory effect is mediated through a type II histamine receptor. The inhibitory effect of histamine on blastogenesis was also reversible by indomethacin, a prostaglandin synthetase inhibitor, implicating prostaglandin involvement in histamine suppression. Histamine release at sites of inflammation may result in down regulation of local immune responses by activation of specific immunoregulatory cells. This could permit the escape of certain neoplasia from local immunosurveillance mechanisms. Cimetidine may block activation of histamine responsive regulatory cells bearing type II receptors, which may help explain the beneficial effect cimetidine therapy has on regression of certain human tumors (i.e., malignant melanomas). PMID- 2316188 TI - The relationship between the concentration of selenium in the blood and the activity of glutathione peroxidase in the erythrocytes of the dromedary camel (Camelus dromedarius). PMID- 2316189 TI - Onchocerca raillieti: release from skin snips, maintenance in vitro and periodicity of microfilariae. AB - Several media were tested for the release of Onchocerca raillieti microfilariae from skin snips and for their subsequent in vitro maintenance. Tyrode's solution containing 20% equine serum and antibiotics was the best medium tested, followed by phosphate buffered saline. Tyrode's solution alone or distilled water were poor media. A temperature 7-12 degrees C lower than the host's body temperature favoured release of the microfilariae from skin snips. The microfilariae were best maintained at 4-10 degrees C, when they remained alive for up to 5 days. O. raillieti microfilariae had an evening periodicity which could be related to a possible vector's peak of feeding activity. PMID- 2316190 TI - The ultrastructure of Strongylus vulgaris-mediated equine chronic mesenteric arteritis. AB - Cells found in the intima and media of the cranial mesenteric artery of a mature mare with chronic arteritis were identified as smooth muscle cells and occurred in association with collagen and elastin fibres. As no fibroblasts were demonstrable within these regions, the smooth muscle cells were the likely source of the extracellular matrix. In contrast, the abnormal adventitis from the same artery contained abundant fibroblasts which are considered to be the source of the adventitial collagen. PMID- 2316191 TI - Pharmacokinetics and distribution of ampicillin in plasma, milk and uterine fluid of female buffaloes. AB - A pharmacokinetic study of ampicillin (6 mg/kg intravenous) revealed that the peak concentrations of 17.81 +/- 1.25, 5.64 +/- 2.24 and 1.09 +/- 0.10 micrograms/ml of the drug were attained at 15 min, 30 min and 2 h in plasma, milk and uterine fluid respectively. A therapeutic concentration of greater than or equal to 0.1 microgram/ml was maintained from 15 min-8 h, 15 min-6 h and 30 min-6 h in plasma, milk and uterine fluid. Hence, the drug may be used effectively in mammary gland and uterine infections apart from its use in other systemic infections. PMID- 2316192 TI - Estimation of the total surface area in Indian elephants (Elephas maximus indicus). AB - Twenty-four adult Indian elephants (Elephas maximus indicus) of both sexes and different ages and weights, belonging to the Temple Devaswoms, the Forest Department of the Government of Kerala and the Gemini Circus formed the experimental subjects from which formulae were derived to predict the total surface area from either body measurements or areas of individual regions. Several models, using the parameters studied either singly or in combination, were tried independently for males and females and also for adults irrespective of sex. The best prediction of total surface area (S) in m2 was obtained for adults irrespective of sex by using the two parameters, the height at the shoulders (H) in m and forefoot pad circumference (FFC) in m in the formula S = 8.245 + 6.807H + 7.073FFC. No significant improvement in the accuracy of prediction resulted from the use of the independent best fit formulae for males and females. The conventional method of using the exponential of body weight (kg) for predicting surface area was not found to yield an equivalent accuracy in these animals. PMID- 2316193 TI - A discriminatory study of a pharmacokinetic model for intramuscular gentamicin in sheep. AB - The resulting serum concentrations were measured in six ewes after intramuscular administration of 10 mg/kg of gentamicin. The model providing the best fit for the experimental data was determined both by linear regression analysis between the experimental and theoretical values and by means of the Minimum Akaike Information Criterion Estimation (MAICE) test. Linear regression analysis showed certain differences favouring the monocompartmental model although the advantage was not conclusive. The MAICE test, however, permitted a clear discrimination in favour of the same model. When linear regression analysis is not conclusive, the MAICE test represents a good alternative. PMID- 2316194 TI - Pharmacokinetics and dosage regimen of cephalexin in buffalo calves (Bubalus bubalis) following single intravenous and intramuscular administration. PMID- 2316195 TI - The effects of age on the erythrocyte sodium and potassium concentrations of dairy cows during late pregnancy and early lactation. AB - Blood samples were taken at weekly intervals from 54 dairy cows (mainly Friesians and Jerseys) during the periods 8 weeks before and 8 weeks after calving. The cows were divided into two age groups; group 1 consisting of 26 cows aged 2 1/2 years and group 2 consisting of 28 cows aged 5-9 years. The changes in the erythrocyte sodium (ENa) and the erythrocyte potassium (EK) concentrations before and after calving were expressed as the slopes for each component regressed on weeks. In the older cows the concentration of ENa decreased (p less than 0.05) while that of EK increased (p less than 0.05) after calving. Both the ENa and EK concentrations varied significantly (p less than 0.01) between cows in the two age groups. The prepartum and postpartum ENa and the postpartum EK concentrations varied significantly (p less than 0.05) between weeks. EK type did not influence the changes in ENa or EK concentrations before or after calving. PMID- 2316196 TI - [The registry status of cancer patients in the USSR in 1985]. PMID- 2316197 TI - [RLadiolymphography with 113mIn-chloride in the diagnosis of the lymphogenic metastases of skin melanomas]. AB - One hundred and thirty indirect lymphoscintigraphies (74 lower and 56 upper ones) using 113mIn-chloride were performed in 121 cases of skin melanoma. Metastatic involvement of lymph nodes was characterized by either increased or decreased accumulation of the radionuclide. The overall accuracy of the procedure was 0.85 for the inguinal, 0.82--iliac and 0.75--for the axillary lymph nodes. PMID- 2316198 TI - [Serum marker changes during the rehabilitative treatment of stomach cancer patients]. AB - The results of rehabilitative treatment received at health resort by 200 gastric cancer patients were studied. In 85 of them, radioimmunoassay was used to measure serum CEA, ferritin and gastrin levels in the course of treatment. CEA and ferritin concentrations in remission patients (12.6 +/- 5.7 ng/ml and 94,6 +/- 15.3 ng/ml, respectively) differed from those in cases of relapse (69.2 +/- 7.1 ng/ml and 361.4 +/- 46.8 ng/ml). It is suggested that serum markers levels be used as criteria of response to treatment and prognosis. PMID- 2316199 TI - [The importance of a sequence of laboratory diagnostic micromethods in detecting tumors in subjects with complaints of functional disorders of the gastrointestinal tract]. AB - The paper is concerned with the diagnostic value of a complex of laboratory micromethods for detection of tumors which were used in 421 subjects who had been endoscopically examined for gastrointestinal discomfort. The methods assured correct diagnosis in 61.1% and gave false-positive results in 35.6%. Ninety-seven percent of the latter group showed preneoplastic lesions of the stomach which must be followed up. Half of the patients with preneoplastic lesions of the stomach revealed changes in the physico-chemical properties of blood similar to those observed in gastric cancer patients. False-negative results were obtained in 3.8% of the whole group (far-advanced cancer). The sensitivity of the suggested complex of micromethods for gastric cancer detection was 86%, reliability--61 and specificity--52%. PMID- 2316200 TI - [The pathogenesis of the Zollinger-Ellison syndrome]. AB - The paper discusses data on 48 cases of Zollinger-Ellison's syndrome. Surgery was performed in 45 patients and ulcerated tumor (UT) found in 32. Tumor was detected in the pancreas (17 cases), duodenum, stomach, liver and parapancreatic fat tissue. Multiple tumors were detected in 3 patients. Twenty-seven percent of UT were genuinely or suspiciously malignant. A histological and clinical classification of gastrin-secreting neoplasms is presented. Surgical treatment for Zollinger-Ellison's syndrome presenting with UT and the results of surgery are discussed. PMID- 2316201 TI - [The effect of a black tea extract on the tumor-like growth of the fungus Fusarium bulbigenum var. blasticola]. AB - The antiblastogenic activity of black tea is predicted with a 98% credibility basing on the observation of its inhibitory or preventive effect on spontaneous or carcinogen-induced tumor development in the culture of mycelial fungus Fusarium bulbigenum var. blasticola. PMID- 2316202 TI - [The organization of breast self-examination among women in the Estonian SSR]. AB - Patients with breast cancer and healthy females (150 in each group) aged 40-64 years were examined to assess the extent of breast self-examination development in Estonia. Breast cancer was detected by self-examination in 82.0% of cases. The occurrence of stage I tumors detected by the physician was comparable to that in the self-examination group. Breast self-examination was practised by 69.3% of healthy females and 42.7% of patients. Most of them had read about the method in the literature. Early detection of breast cancer can be assured provided breast self-examination is performed regularly. PMID- 2316203 TI - [The treatment of laryngeal cancer by using local hyperthermia]. AB - Potentiation of the effect of radiation and combined treatment of laryngeal cancer by local hyperthermia was studied in 43 patients. In 51 cases of the control group (radiotherapy), conventionally-dynamic fractionation of dose was used. At 32 Gy, complete or partial regression of tumor was observed in 72.1% in the study group and 64.7% of controls. An increased frequency of radiation induced damage of the oral mucosa was observed whereas radiation epidermitis did not occur. Three-year relapse-free survival following a course of radical thermoradiotherapy was as high as 76.5% compared to 40% in controls. Overall three-year survival (including the results of combined treatment and treatment for relapse) increased from 66.7 to 83.3%. PMID- 2316204 TI - [The psychological aspects of the rehabilitative treatment of patients operated on stomach cancer]. AB - Psychic status was evaluated in 250 radically operated patients with gastric cancer at different stages of treatment (inpatient hospital-health resort outpatient hospital) and adequate therapy was administered. Timely correction of depression proved a component of complex treatment of postresection disorders in gastric cancer patients. PMID- 2316205 TI - [Integral spectrofluorimetry in the diagnosis of jaundice of tumor origin]. PMID- 2316206 TI - [Inflammatory polyp of the ileum complicated by invagination]. PMID- 2316208 TI - An improved assay for human tetanus anti-toxin and its use in the accession of human plasma for the production of high-titre tetanus immunoglobulin. AB - A simplified passive haemagglutination (PHA) screening test, an improved quantitative PHA assay, and a stable test cell preparation are described, as well as a comprehensive testing strategy which have been used in concert at this Service over the past 10 years for the successful accession of high-titre tetanus anti-toxin (TAT) plasma for fractionation into human tetanus immunoglobulin (HTIG). The sequential deployment of the screening and quantitative assays, has permitted large numbers of donors to be screened quickly and economically, and has helped establish a significant core of regular donors with high TAT levels. The assays have proven to be highly sensitive and specific and relatively simple to perform, while the coated cells are inexpensive and easily prepared. Approximately 20% of donors screened from the Sydney metropolitan area had TAT levels of 3 IU/ml or greater. PMID- 2316207 TI - Development of an immunoaffinity process for factor IX purification. AB - An immunoaffinity process based on monoclonal antibody (MAb) to factor IX (FIX) has been developed. Initially, vitamin-K-dependent proteins from cryoprecipitate poor plasma are isolated on DEAE-Sephadex. The eluate is applied to an immunoaffinity column that utilizes a divalent metal-ion-dependent MAb directed against FIX. After washing the column with high salt in the presence of magnesium ion, the FIX is eluted using a citrate- or EDTA-containing buffer. Coagulation assays and Western blots show no detectable amounts of any contaminating proteins. Purity of the FIX product is established using reduced and nonreduced Coomassie-stained SDS-PAGE and HPLC. The N-terminal 20 amino acids of the single peak of the HPLC were shown to be identical to those reported for FIX. The process shows no detectable leakage of monoclonal antibodies (MAb), efficient utilization of MAb, and provides yields greater than 95%. The use of solvent/detergent treatment as a potential viral inactivation methods is incorporated in the process. Studies with tritiated Triton X-100 indicate that the detergent can be washed out of the MAb column so that less than 1 ppm (total) Triton X-100 coelutes with the FIX. PMID- 2316209 TI - The platelet storage capability of different plastic containers. AB - Platelet concentrates (PC), prepared by platelet apheresis, were stored in four different types of blood bags. One of the bags, manufactured with a thinner PVC film than previously, was tested in three different bag volumes. From 25 donors a total number of 99 PC were prepared. Platelet numbers varied from 20 to 140 X 10(9) platelets per bag. The cell count, pH, pO2, pCO2 and lactate were determined initially and on days 1, 3 and 5 of storage. In a separate test, the oxygen diffusion capacity of the bags was determined by oxidation of sodium sulfite in the presence of cobaltous chloride. The oxygen diffusion capacity found was 16 (PL 732, 300 ml), 13.5 (Teruflexa 800 ml), 11.5 (PL 1240, 400 ml), 10.6 (Teruflexa 600 ml), 9 (Teruflexa 400 ml) and 4 (PL 146, 300 ml) mumol O2/h, respectively. For each bag type, the minimum and maximum platelet number stored with maintained pH levels (6.9-7.4) was defined. The maximum platelet number stored with maintained aerobic metabolism, correlated to the oxygen diffusion capacity of the bag, r = 0.998, p less than 0.001, n = 6; thus the maximum platelet number successfully stored for 5 days in each container can be predicted by determination of the oxygen diffusion capacity. In PC with a low platelet yield, pH values above 7.4 were observed after 1 and 3 days. When the results are compared with platelet yield data from routine blood banking, the optimal bags for platelet storage can be chosen. These conclusions must be further investigated in studies in vivo. PMID- 2316210 TI - Management of fetal alloimmune thrombocytopenia by weekly in utero platelet transfusions. AB - Alloimmune neonatal thrombocytopenia (ANT) may cause intracranial haemorrhage in utero as well as at delivery. Recent management has concentrated on attempts to minimise fetal thrombocytopenia and prevent its complications. This report describes further experience with the use of repeated intravascular transfusions of compatible platelets in utero. The patient studied had already had one infant with intracranial haemorrhage due to ANT. In her next pregnancy, weekly intra uterine platelet transfusions were given from 26 weeks, but intra-uterine death occurred at 30 weeks after the mother had a heavy fall. In her most recent pregnancy, weekly intravascular transfusions of platelets were given by cordocentesis from 29 to 34 weeks. The fetal platelet count was maintained above 30 X 10(9)/l for almost all of the last 6 weeks of pregnancy before delivery of a normal infant by Caesarean section at 35 weeks' gestation. This approach is effective in preventing severe fetal thrombocytopenia in the last trimester of pregnancy and is contrasted with alternative treatments of ANT. Further data are required to determine the efficacy and risks of these treatments. PMID- 2316211 TI - Red cell alloantibodies in patients with thalassemia. AB - We present the results of tests carried out to detect alloimmunization against red cells in 1,200 patients (607 males and 593 females), transfused and followed up during the period 1981-1987 in our hospital. Of these patients, 1,135 were thalassemic and 65 had sickle cell/beta-thalassemia. In 162 patients who received blood matched for the AB0, rhesus and Kell systems from their first transfusion, the immunization rate was very low (3.7%). In a pilot group consisting of 83 patients with the same clinical characteristics, who received blood matched only for the AB0 and Rh-D antigens, there was a significant difference in the frequency of alloantibodies (15.7%, p less than 0.001). Of 1,038 patients who received blood only matched for AB0 and Rh-D 244 (23.5%) with one or more red cell alloantibodies were identified. Of these 1,038 patients, 973 were exclusively thalassemic. In 220 (22.6%) of them, alloantibodies were found. The sickle cell beta-thalassemia patients presented alloantibodies with a higher frequency (36.9%, 24/65). Only one antibody was found in 114 patients (51.8%) and two or more in 106 patients (48.2%). The alloimmunization significantly concerned the rhesus (34.0%) and Kell (29.8%) systems. Anti-Kell was most often identified (28.5%). Alloimmunization appears considerably lower in patients in whom blood transfusion is started before the age of 3 than in those in whom it is started after that age (20.9 vs. 47.5%, p less than 0.0001). PMID- 2316212 TI - Evidence that the Auberger blood group antigens are located on the Lutheran glycoproteins. AB - Immunoblots of red cell membranes stained with eluates of alloanti-Aua and alloanti-Aub show that these antibodies recognize 2 membrane components from Au(a+) and Au(b+) cells, respectively. These structures, of apparent molecular weight (Mr) 79,000 and 85,000, are identical in appearance and mobility on a 10% SDS polyacrylamide gel to the Lutheran glycoproteins identified by alloanti-Lub. Like the Lutheran glycoproteins, they showed a reduction in apparent Mr of about 1,500 after sialidase treatment. Red cell membrane components immunoprecipitated by a Lutheran-related monoclonal antibody, were analysed with Lutheran and Auberger antibodies by immunoblotting. The Lutheran glycoproteins were revealed by anti-Lub in precipitates from Au(a+b-) Lu(a-b+) and Au(a-b+) Lu(a-b+) cells, by anti-Aua in precipitates from Au(a+b-) Lu(a-b+) cells and by anti-Aub in precipitates from Au(a-b+) Lu(a-b+) cells. The same components were also recognized by anti-Lua in precipitates from Lu(a+b-) cells. Thus Aua and Aub antigens appear to be carried on the same red cell membrane structures as those carrying the Lutheran determinants. These results are particularly significant in the light of the very close phenotypic association between the Auberger and Lutheran blood groups which have been shown, by one family, to be controlled by genes at separate loci. PMID- 2316213 TI - Investigation of Lewis phenotypes in Polynesians: evidence of a weak secretor phenotype. AB - The salivary ABH and Lewis antigens of Polynesians were measured using a standardised red cell agglutination microplate assay and compared with the red cell defined Lewis phenotypes. Salivary ABH substances were detected in almost all saliva samples tested, with low levels (partial secretion) of ABH substances in the saliva from Le(a+b-) and Le(a+b+) individuals. Salivary Leb substance was detected in all Le(a-b+) and Le(a+b+) samples and in almost all Le(a+b-) samples. It is evident from the results obtained that Polynesian red cell phenotypes cannot be used to predict the presence or absence of salivary substances. If the presence of a coding secretor gene is presumed responsible for salivary ABH antigens and salivary Leb antigen expression, then the incidence of a coding secretor gene in Polynesians is 98%. These results indicate that the recessive non-secretor gene is absent or rare in a Polynesian derived gene pool. Two variants of secretor individuals are found among Polynesians, secretors with expression of normal amounts of the product of the secretor gene, similar to Caucasians, and partial secretors with weak expression of the secretor gene products. PMID- 2316214 TI - Retrospective screening for HTLV I infections in 68 acute leukemic patients multiply transfused before 1985. PMID- 2316215 TI - Haemolytic disease of the newborn due to anti-k. PMID- 2316216 TI - Heterogeneity of anti-U. PMID- 2316217 TI - White Paper, SB-576. PMID- 2316218 TI - The White Paper. PMID- 2316219 TI - Microvascular free tissue transfers. AB - Despite complex massive defects, reconstruction can be reliably undertaken with microvascular free tissue transfers. In a single stage, this technique permits restoration of composite tissue loss, restoration of function, and acceptable aesthetic results. When confronted with extensive tissue loss, a multidisciplinary team approach is optimal. The risk associated with sophisticated reconstructive procedures is justified when managing these patients. The success of these procedures allows a better quality of life by reestablishing function and maintaining acceptable aesthetic appearance. PMID- 2316221 TI - Blood rheology during induced ischaemia of the lower limbs. AB - The filterability rate of whole blood, the red and white blood cell sub populations, and the erythrocyte and leucocyte count variations were studied during exercise in 20 male non-diabetic smokers, all with Stage II peripheral vascular disease (PVD), and 20 matched controls. A controlled ischaemia was induced using treadmill exercise. Blood samples were taken at rest, at the onset of calf pain and at haemodynamic recovery from peak exercise. Leucocytes were counted, separated using Ficoll-Hypaque into their sub-populations by centrifugation, and adherence to Petri dishes, re-suspended in buffer and filtered through 5 micron pore diameter filters. Whole blood filterability and the leucocyte count were significantly increased at the onset of calf pain. A significant increase was observed in the filterability of the monocyte sub fraction and this persisted throughout the recovery period. PMID- 2316220 TI - [Left ventricular function in young type I diabetic patients. A Doppler echocardiography study]. AB - Systolic and diastolic left ventricular function was assessed by M-mode and pulsed Doppler echocardiography in 10 young type I diabetic patients without late complications and maximal diabetes duration of 5 years and in 10 healthy persons. Fractional shortening, a measure of systolic ventricular function, was significantly lower in diabetics than in controls (33.9 +/- 2.9 vs. 37.9 +/- 4.9; p less than 0.05). Fractional shortening decreased significantly with advancing diabetes duration (R = -0.819; p less than 0.01). Indexes of diastolic ventricular function (isovolumetric relaxation period and transmitral flow velocity pattern) were not significantly different in the two groups, but 3 patients had 1 parameter (3x isovolumetric relaxation period) and another patient had 2 parameters (isovolumetric relaxation period and early diastolic peak velocity E-E') outside the normal range. Follow-up studies should define the clinical significance of these alterations of systolic and diastolic left ventricular function. PMID- 2316222 TI - [Hemolyzing antibodies to markers of the P blood factor system as a problem in blood transfusion and pregnancy. With reference to serology, biochemistry and genetics]. AB - The extremely rare phenotypes p, P1k and P2k (0.0005-0.0006%) of the blood group P system are usually found in consanguinous families. In the serum of these persons haemolytic antibodies with the specificity anti-PP1Pk and anti-P are found, causing severe haemolytic reactions after transfusion of incompatible blood. Because of their rarity it is difficult to find compatible blood donors. The antibodies are also associated with abortion early in pregnancy. Since 1948 at the "Institut fur Blutgruppenserologie der Universitat Wien" 4 persons of the phenotype p and 3 of the type P2k were observed in altogether 5 families. Two of them needed blood transfusions, the one p patient received p blood from her sister, who likewise gave blood to the other p patient. This latter patient additionally received three blood units which had been stored in liquid nitrogen and came from Austria and from the European bank of frozen blood in Amsterdam (Council of Europe). The pedigrees of three families with 5 probands out of the 7 observed cases could be reconstructed and showed consanguinity, partly some generations back. A genetic model valid at the moment for the biosynthetic pathway of the P antigens is demonstrated and the appropriate serological characteristics of the haemolytic antibodies are shown. The seven antibodies are partly IgG and partly IgM antibodies, optimally reacting using the indirect antiglobulin test or enzyme-treated red cells. The range of the antibody titres was between 1:8 and 1:1024. Absorption of Anti-PP1Pk sera with red cells of type P1 to get Anti-Pk and inhibition with hydatidcyst fluid and globoside to receive Anti-P and Anti-P1 + Pk, respectively were partly successful. PMID- 2316223 TI - [24-hour blood pressure determination in Shy-Drager syndrome. A case report]. AB - The case history is presented of a 57 year-old male patient suffering from the Shy-Drager syndrome. This syndrome was first described by G. M. Shy and G. A. Drager in 1960. The clinical manifestations are extrapyramidal, with Parkinsonian features, combined with severe orthostatic hypotension and failure of the autonomic nervous system. Apart from the standard clinical investigations in this condition, namely the orthostasis test and polygraphic recording of the EEG, ECG, breathing and blood pressure on the tilting table, additional non-invasive long term determination of the blood pressure was carried out. This method allows simultaneous measurement of blood pressure and heart rate without appreciably interfering with the patient's daily activities. PMID- 2316224 TI - [Prevalence of HIV-1 infection in intravenous drug dependent patients 1986 to 1989 in Vienna]. AB - We report the results of a survey of a total of 553 intravenous drug users (IVDUs) investigated at the drug addiction out-patient unit of the Psychiatric Department of Vienna University for antibodies to human immunodeficiency virus (HIV-1) using both enzyme-linked immuno sorbent and Western blot assays. HIV-1 antibodies were found 1985/86 in 8.5%, 1986/87 in 14.5%, 1988 in 27.7% and 1989 in 29.7% of IVDUs. The introduction of methadone maintenance in 1987 attracted many IVDUs and increased the number of patients at the out-patient clinic. In 1989 more than 50% of the IVDUs are on methadone maintenance and already 84.5% of the HIV-1 infected drug users are treated with methadone. PMID- 2316225 TI - [Air pollution and sudden infant death in Graz 1982 to 1987]. AB - We correlated the incidence of the sudden infant death syndrome (SIDS) and the degree of air pollution in each district of Graz over a time period of five years. The degree of air pollution was derived from a mapping of epiphytical lichen vegetation by Grill et al. (1988). We found an increased incidence of SIDS in districts with poor air quality. Although this result is not statistically significant a possible increase in SIDS risk because of air pollution cannot be excluded. Some pathophysiological explanations are discussed. PMID- 2316226 TI - [In vitro sensitivity of Aeromonas spp. to antibiotics]. AB - Aeromonas strains, isolated from stool samples and aquatic biotopes were tested for their susceptibility to 20 antibiotics. The beta-lactamase-resistant cephalosporins, imipenem, aminoglycosides, ciprofloxacin, tetracycline, chloramphenicol and sulfamethoxazole + trimethoprim are highly efficient. PMID- 2316227 TI - [Clinical aspects and therapy of gallstone ileus]. AB - High lethality of gallstone ileus can be reduced by prompt diagnosis and careful treatment. Aerobilia is of great diagnostic value, in doubtful cases Gastrografin passage of the intestine is useful. Enterolithotomia alone is the least dangerous treatment. However, postoperatively the possibility of a recidive should be kept in mind. PMID- 2316228 TI - Characterization of dexamethasone binding in normal and uremic human serum. AB - The purpose of this study was to examine the extent and linearity of dexamethasone binding over a wide concentration range in normal and uremic serum. Tritiated dexamethasone was added to both untreated and charcoal-treated pooled normal serum and to pooled uremic serum to produce concentrations similar to those attained therapeutically (10-1000 ng/mL). Protein binding was determined by equilibrium dialysis at 37 degrees C. Dexamethasone serum binding was linear over the entire range of concentrations for each set of pooled serum. The mean (+/- SD) percent bound (mean +/- SD) for dexamethasone was similar for untreated (75.1 +/- 3.6 percent) and charcoal-treated (77.3 +/- 3.5 percent) normal serum. Dexamethasone binding (69.2 +/- 1.8 percent, p less than 0.05) and serum albumin concentrations (39.9 vs. 55.1 mmol/L) were significantly less in uremic vs. normal serum, respectively. These results suggest that (1) the binding of dexamethasone is linear and occurs primarily to albumin, with little or no binding to corticosteroid-binding globulin; (2) endogenous cortisol does not compete with dexamethasone for protein binding sites; and (3) steroid pharmacokinetics may be altered in uremic patients due to the 24 percent higher free fraction of dexamethasone in this population. PMID- 2316229 TI - Prolonged labetalol infusion for management of severe hypertension and tachycardia in a critically ill trauma patient. AB - A trauma victim sustained multiple injuries including cervical spine injuries, splenic laceration, and left kidney fracture. His recovery was complicated by acute renal failure, resistant hypertension, and tachycardia refractory to multiple therapies. The patient was ultimately managed with continuous infusions of labetalol 2-3 mg/min for 14 days, with adequate control of both blood pressure and heart rate. The sustained labetalol infusion was not associated with clinically significant adverse effects although a progressive decrease in heart rate was noted near the end of therapy. This downward trend in heart rate was not associated with hemodynamic compromise and returned to pretreatment baseline of 90-110 beats/min upon discontinuation of parenteral therapy and initiation of oral labetalol. The prolonged use of labetalol infusions may be beneficial in certain patients. Further work needs to be done to identify the safety and efficacy of labetalol infusions. PMID- 2316230 TI - Severe hypomagnesemia induced by pentamidine. AB - The use of pentamidine for treating Pneumocystis carinii pneumonia in AIDS patients has increased the awareness of pentamidine-induced adverse reactions. We report a case of severe hypomagnesemia and concurrent hypocalcemia that occurred during therapy with intravenous pentamidine. Pentamidine therapy was subsequently changed to the nebulized route. Electrolyte imbalances were corrected after daily supplementation with high doses of magnesium and calcium. Clinicians should monitor for electrolyte imbalances which can be severe in patients receiving prolonged courses of pentamidine therapy. PMID- 2316231 TI - Perphenazine-induced priapism. AB - A 29-year-old man experienced four episodes of prolonged painful erection while being treated with perphenazine for paranoid schizophrenia. Each episode of priapism lasted five hours or longer. On two occasions, aspiration of blood from the corpora cavernosa resulted in detumescence; the other episodes were successfully managed with operative shunting of blood from the congested cavernosa. Perphenazine was discontinued after the fourth episode of priapism and antipsychotic treatment with thiothixene was subsequently initiated. During 16 months of follow-up, the patient has reported normal erections without repeat episodes of priapism. PMID- 2316232 TI - Symptomatic hypoglycemia secondary to a glipizide-trimethoprim/sulfamethoxazole drug interaction. AB - Sulfonamides have been reported to augment the hypoglycemic effects of chlorpropamide, glyburide, and tolbutamide. This case report is the first to describe a possible interaction with glipizide. An 83-year-old man receiving glipizide 10 mg bid developed symptomatic hypoglycemia within three days of adding trimethoprim/sulfamethoxazole (TMP/SMX) to his regimen. All other factors, including laboratory data, dietary intake, activity level, and concurrent use of other medications, were stable and noncontributory. This patient may have been at increased risk for this interaction secondary to his age and history of alcohol abuse. The mechanism of the interaction is probably inhibition of glipizide metabolism rather than protein-binding displacement. This case suggests that, when TMP/SMX is combined with glipizide, patients should be closely monitored, especially those at high risk for hypoglycemia. PMID- 2316233 TI - Effect of aluminum hydroxide gel on quinidine gluconate absorption. AB - The effect of aluminum hydroxide gel on quinidine gluconate bioavailability was studied in eight nonsmoking healthy male volunteers. Subjects were randomized to receive quinidine gluconate 648 mg with and without 30 mL of aluminum hydroxide gel. The mean area under the concentration-time curve (AUC) (23.11 +/- 5.21 mg.h/L), time to reach maximum concentration (tmax) (3.13 +/- 0.64 h), maximum serum concentration (1.44 +/- 0.41 mg/L), and elimination rate constant (0.069 +/ 0.010-h) observed during the control phase of the trial did not differ significantly (p greater than 0.05) from values obtained during the coadministration of aluminum hydroxide with quinidine gluconate (23.91 +/- 4.48 mg.h/L, 4.13 +/- 2.12 h, 1.53 +/- 0.34 mg/L, and 0.077 +/- 0.013-h, respectively). There was considerable individual variation in AUC with one subject demonstrating an increase of 35 percent and one subject demonstrating a decrease of 18 percent. There was a trend toward aluminum hydroxide delaying tmax with only one subject experiencing an earlier tmax with the coadministration of aluminum hydroxide. The results of this single-dose trial suggest that, although statistically the concurrent administration of aluminum hydroxide gel with quinidine gluconate does not significantly alter the extent of quinidine absorption, clinically significant individual variations may occasionally occur. PMID- 2316234 TI - Omega-3 fatty acid supplementation in noninsulin-dependent diabetes. PMID- 2316235 TI - Aminoglycoside volume of distribution in pediatric patients. AB - Pharmacokinetic parameters of three aminoglycoside antibiotics were studied retrospectively in 218 pediatric patients to determine an apparent volume of distribution (Vd) for this age group and to determine if Vd is significantly different in pediatric patients compared with adults. Data on patients considered for inclusion in the study were obtained from the files of the aminoglycoside monitoring services at Saskatoon University Hospital and Regina General Hospital. Both services use a computer program that calculates pharmacokinetic parameters using the Sawchuk-Zaske method. Children between the ages of 1 and 16 years with normal renal function from whom serum concentration had been obtained were included in the study. Exclusion criteria included abnormal or unstable renal function, cystic fibrosis, and pregnancy. The mean age of the pediatric group was 8.65 +/- 5.37 years. Average values for Vd and half-life were 0.34 L/kg and 2.3 h, respectively. No strong correlation was found between the Vd (L/kg) and age. The patients were subdivided into three age groups: 1-4.9 years, 5-9.9 years, and 10-16 years. Group 1 (1-4.9 years) had a larger Vd than the other groups and the Vd of all three groups were significantly different from the estimated Vd of 0.20 L/kg for adult patients. A "normal" pediatric value for the Vd of aminoglycosides could not be determined; however, the Vd in children is significantly larger than the Vd in adults and dosage regimens should be adjusted accordingly. PMID- 2316236 TI - Effect of cimetidine on oral digoxin absorption. AB - Cimetidine is a commonly prescribed histamine 2-receptor antagonist used in the treatment of gastric acid-related disorders. Cimetidine can interact with a number of drugs, including theophylline, benzodiazepine sedative hypnotics, warfarin, and antiarrhythmics. Problems may occur in patients receiving drugs with a narrow therapeutic index when combined with cimetidine. Contrasting reports have been published on the potential interaction between digoxin and cimetidine. This study focuses on cimetidine's effect on the pharmacokinetic disposition of chronic digoxin usage. Six hospitalized patients with stable congestive heart failure received their usual maintenance dose of digoxin 0.125 0.25 mg/d po. After confirming steady-state digoxin concentrations, cimetidine 300 mg po q6h was administered. Two patients were dropped from the study. Analysis of digoxin serum concentrations, area under the curve, and the rate of elimination suggested no significant differences in digoxin parameters when combined with cimetidine. PMID- 2316237 TI - Effect of a clinical pharmacist program on the cost of hypertension treatment in an HMO family practice clinic. AB - This study evaluated the impact of a clinical pharmacy service on the cost of antihypertensive drug therapy in an HMO family practice clinic. The service was provided to five family practice physicians. Pharmacists identified hypertensive patients prior to their regularly scheduled office visits from April through June 1986. Patient's medical records and computerized drug files were reviewed, and written recommendations for drug therapy changes were placed in patients' medical record by the pharmacists. When appropriate, pharmacists alerted prescribers to lower cost alternatives. A matched control group of physicians was selected. Hypertensive patients were identified retrospectively in the control group. We found that the cost of antihypertensive drug therapy was significantly higher for study physicians' patients when compared with control physicians' patients in the period prior to implementing the service. The difference between the two groups was not significant after six months. Clinical pharmacist intervention decreased the average cost of antihypertensive treatment from 33.4 to 27.2 cents per day. PMID- 2316238 TI - Adjusting for clustering in survey research. AB - The current widespread application of cluster sampling in survey design presents concerns to the researcher regarding the chosen unit of study. The statistical power of a study could be spuriously increased or decreased, sample size could be altered dramatically, and the uniqueness of the individual unit under study (e.g., a patient) could be lost and substituted by average values of characteristics depending on which unit of study is selected. The 1985 National Ambulatory Medical Care Survey of the U.S. National Center for Health Statistics was used to illustrate research methodologies that would deflate spuriously high results due to clustered sampling. Using the individual patient as the study unit, correction factors ranging from 1.99 to 35.40 were calculated in order to deflate exaggerated t-tests, chi-square, and F values of predictor variables. The effect of clustering was more marked on (1) continuous rather than binary outcome variables, as the former provide a richer environment to form clusters; and (2) on outcome variables relating to the practice-related or personal style of physicians. Using the physician (who represented a cluster of patients) as the unit of study, it was realized that correction factors were relevant to physician specific predictors but not patient-specific predictors. Using design effect correction factors developed from a simple univariate analysis of variance, pharmacoepidemiologists can analyze accurately the currently available large survey databases of clustered samples. PMID- 2316239 TI - Polypharmacy in the elderly: a fait accompli? PMID- 2316241 TI - Lorazepam and sleep quality. PMID- 2316240 TI - Theophylline plasma concentrations and silicone central venous catheter: a potential source of error. PMID- 2316242 TI - Lorazepam dosing in neonates: application of objective sedation scores. PMID- 2316243 TI - Bethanechol-induced cholinergic toxicity in diabetic neuropathy. PMID- 2316244 TI - Serum concentration of alpha 1-acid glycoprotein and albumin following cesarean section and vaginal delivery. PMID- 2316245 TI - [Emergencies and management by the family practitioner]. AB - 4.6% of all consultations realized by family doctors (including consultations in the doctor's practice, visits to the patients' homes, medical on-call service) can be characterized as emergency consultations. In the provision of health care by family doctors those circumstances that require medical intervention without delay are to be characterized as emergency situations (even if life is not immediately threatened). 11.6% of all emergency calls are made because of a cold (in particular, in the case of small children) or a hurt (open wound, contusion, or fracture). According to physicians, 54.5% of the emergency consultations were based on urgent circumstances. In those cases where only life-threatening circumstances were registered as emergency cases, 15.2% of the above percentage of emergency consultations were underestimated by the patients as to their urgency. PMID- 2316246 TI - [Diagnoses in the medical house call]. AB - 8.6% of the inhabitants of a rural community called for a physician's visit to their homes during a period of 12 months. 2.9% of the population were medically attended to exclusively in their homes. Health care in the patient's home is above all provided to chronically ill, disabled and care-needing persons at old age (73.8% of all visits to the patient's homes). Almost 50% of all visits to the patient's homes are made to elderly women because of diseases of the circulatory system. Geriatric issues are predominant in health care in the patient's home. The ranking order of the diseases most frequently diagnosed in the patient's home differs from that observed in the General Practitioner's consultations. Hospitalizations resulting from visits to the patient's home have, as a rule, the nature of emergency measures. The need for a visit to a patient's home is determined more often by the patient's state of health rather than by nosologically oriented diagnoses. Medical diagnoses made in the patient's home characterize the care situation at home only to a limited degree. PMID- 2316247 TI - [Management of elderly citizens in a residential setting]. AB - On the basis of demographical and social developments as well as of the "demand" for nursing resources in the GDR, the medical and social care situation for the elderly is discussed with special emphasis on the responsibilities of the family practitioner. Concluding from our own investigations we propose to use the Classification of Disabilities for deducing indications of care activities and standards. Examples are given, in particular, in respect of differing forms of protected lodging of care-needing elderly citizens. PMID- 2316248 TI - [Responsibilities of the district physician in managing severely ill psychiatric patients at institutions]. AB - 574 individuals with heavy psychical impairments living in psychiatric clinics have been examined and their impairments diagnosed in a differentiated way. Conclusions are drawn as for the organization of the contents of care activities. Care should be, in principle, aimed at rehabilitation. The necessary material an human resources are to be created. PMID- 2316249 TI - [Managing severely ill psychiatric patients at nursing homes]. AB - Different conditions of care for individuals with chronic psychical impairments are discussed and explained by investigations into the care situation in clinics and facilities with protected work. The author demonstrates that care should be provided on the basis of individually existing disabilities with rehabilitative activities playing an essential role. Protected work is of paramount importance. PMID- 2316250 TI - [Management and organization of ambulatory medical care in a district]. AB - An analysis is given of the management and organization of out-patient medical care in 15 districts and of the District Physician's responsibilities as well as the profile of a District Health Department. Compared to the situation of a decade ago, substantial changes in the territorial health organization have occurred (decentralization, formation of care areas, affiliation of small health facilities to bigger ones). The District Physician's scope of responsibility is increasingly determined by activities within the framework of the District Council, the proportion of organizational work has increased. In order to be able to fulfill his tasks the District Physician needs the support of a special Health Department. Skeleton regulations for out-patient medical care are necessary. PMID- 2316251 TI - [Effect of health behavior on health status--social medicine problems in family practice management]. AB - Health counselling as a part of the family doctor's practice includes the influence of health behaviour on the state of health. Health behaviour is transmitted by relational persons within everyday social groups. It depends on the scale of values and norms of behaviour within a group and is modified by individual needs. Vital social contacts (family and relational persons) have a higher value than health and serve-depending on the structure of personality-as a motivation of a health-promoting lifestyle. The family doctors strategies of intervention are aimed at winning relational persons, group leaders and local personalities to encourage health promotion and thus achieving that a healthful lifestyle is supported by the public opinion and becomes the social standard. PMID- 2316252 TI - [Taste disorders in chromium exposed workers]. AB - Taste thresholds were investigated by means of chemical and electric stimulation in order to prove the induction of taste disturbances by chrome dust. There were examined 46 persons with exposition by potassium bichromate, chromic acid and zinc chromate, 19 of them working under conditions of a lower chrome exposition level but 27 of them working under conditions of a higher chrome exposition level. We could find a increasing threshold in taste qualities "sweet", "poor", "salty" and "bitter" corresponding to an increase of chrome exposition on the one hand and likewise of electric stimuli on the other hand. The quantity of chrome exposition must be regarded more important than its quality and its duration. Finally we want to recommend the appliance of always as electrogustometry as chemogustometry for occupational taste investigations because both the methods seem to differ somewhat. PMID- 2316253 TI - [Specialty specific reference values in linen use in public health and social service as a basis for determining laundry capacities]. AB - The use of linen in health and social care should primarily be seen from a hygienic angle. Disproportions between the use of linen in the various fields of health care and the available laundry capacities have a negative hygienic and economic effect. Laundry capacities should, therefore, be calculated on the basis of specialty-specific guidevalues. The authors propose indicators suitable to this aim and present the results of a comprehensive analysis for the inpatient departments of internal medicine, surgery, urology, ophthalmology and otorhinolaryngology. PMID- 2316254 TI - [Analysis of economic management as an aid for directing and planning health care facilities]. AB - Analyses of hospital processes are of vital importance to management decisions in health facilities. The number of indicators to provide a meaningful analytical basis for decision making should be kept as small as possible. An increased use of modern electronic data processing systems will result in a qualitative improvement of facility-related information systems for managing and planning purposes. The example of an internal department of a district hospital shows that a small number of basic indicators is sufficient for facilitating efficiency and capacity analyses in in-patient units. PMID- 2316255 TI - [Hearing loss of workers in mining--a 6-year longitudinal study]. AB - Hearing threshold level (HTL) in miners, was determined after six years interval characterized by the same noise exposure. An attempt was made to establish the prognosis regarding the hearing losses extent and the time interval involved in the occurrence of these modifications in the subjects applying the HTL values. 132 workers (miners and miner apprentices) underwent audiometrical examinations, after 6 years interval in the same testing conditions. To evaluate the vibrations possible effects on the HTL, the results registered in a group of workers exposed solely to noise (n = 33)-identical continuous equivalent level/week-were compared to those found in miners. According to age range and the duration of noise exposure, the yearly mean rate for both the low (500-2000 Hz) and high frequencies (2-8 kHz), were calculated based on the hearing threshold differences. The miners, simultaneously exposed to noise and vibration presented yearly decreased HTL values (up to 2000 Hz), as against the subjects exposed solely to noise. The prognosis indicates that in a miner with a duration of exposure above 21 years and/or a mean age of 38, one may expect a loss of the HTL exceeding 30 dB at 4 kHz. PMID- 2316257 TI - [Ergo-ophthalmologic aspects of work responsibilities with high visual requirements]. AB - Visual requirements, in the case of modern technologies, are concerned in particular with control and regulation mechanisms of the visual system. For this reason differentiated analyses of visual requirements are necessary along with comprehensive optometrical care. In the latest official sight capacity criteria D 77, account is taken of these points. Measurements of the strain experienced, the routine of breaks during working hours and the extension of optometrical methods are therefore subjects of current research. Attention needs to be paid to raising the qualification levels and to finding new partners for cooperation. PMID- 2316256 TI - [Occupational medicine outpatient management of workers with responsibilities involving great psychological stress]. AB - Some selected results from regular medical occupational fitness evaluations, the statistic of unfitness for work, the disablement of teachers and the occupational referred mortality were demonstrated in special consideration of workers with particular psychic load. From it conclusions were drawn for the development of methods for occupational medical fitness examinations and check ups, prophylactic and therapeutic programmes. The necessarity of scientific dealing with this problems was emphasized. PMID- 2316258 TI - [Meteorologic effects on dental pain conditions]. AB - Cases of treatment because of acutely occurring states of pain were analysed in a big-city dental outpatients department. The one-year examination covered about 4,000 cases of the total number of 40,000 consultations. As for the diagnoses considered in the examination, it concerned primarily dental caries, acute apical periodontitis and pulpitis. It was to find out if here is a relation between "toothache" and airhygienic influences. This was done with reference to an examination using the same method which was performed as early as in 1982/83. Apparently, there is no immediate correlation. PMID- 2316259 TI - [A responsibility key for personnel in health and social service as an aid for occupational medicine epidemiology]. AB - Staff members of the public health service were examined referring to problems of industrial epidemiology. This examination requires the consideration of activity and branch of study of the people involved. A system of itemization used for encoding is explained. Results of application are introduced with occupationally caused allergy to formaldehyde serving as example. In addition, further possibilities of application are shown. PMID- 2316260 TI - [Functional changes of the cervical spine and shoulder-neck region in workers employed in textile sewing]. AB - Functional disturbances of cervical spine, shoulder-nape-muscles and cervicothoracic ligamentous apparatus were examined in 100 needle-women. 105 nurses from outpatients departments served as group of comparison. In consideration of signs of occupational load clues to occupationally caused overstrain were found. PMID- 2316261 TI - [Computer-assisted evaluation of emission data]. AB - To estimate the hygienic relevance of a given air pollution situation the knowledge of the quantiles of an ensemble of measuring data is very important. A computer programme to determine the quantiles is presented. In addition to the usual method of ranking data it allows the calculation by use of the Weibull distribution function, which is important in the case of a small data set. First results of practising on this software are discussed. PMID- 2316262 TI - [Collaboration between the specialist in general medicine and pediatrics in the rural area with special emphasis on informational relations]. AB - An analysis is made of the scope of health care performances provided by family practitioners and paediatricians to children in a mountainous community (of the Erzgebirge), with special regard to the informational relations existing in the community. The survey is, in the main, a two-stage interval investigation. At the first stage, a description is given of the high share the family practitioner has in the health care performances provided to children (preventive care: 100%; curative care: 95.4%, about 60% of which require the occasional collaboration with the paediatrician). At the second stage, an informational sheet is used, which not only permits complete feed-back information from the paediatrician but also increases the referral rate, multiplies the back referral rate and improves the quality of health care in general. This model is recommended for use by analogous territories. PMID- 2316263 TI - [Time factors in endoscopic studies. A survey in West Germany]. AB - In order to obtain representative data for the orientation of personal requirements in endoscopic units, 650 hospitals in the FRG were asked to have an exact look at the times they needed for endoscopic procedures during an period of 14 days. 25% of the contacted hospitals answered to this request and thus the times required for more than 14,000 endoscopic procedures for both, doctors and medical staff, could be analysed. Results revealed that most of the sophisticated procedures such as colonoscopy, ERCP (especially when they included therapeutic endoscopical methods) varied largely in time. This was caused by different factors such as the patient dependent variables, and the course of the procedure including observation of safety and hygiene standards. Average values of times needed for endoscopic procedures were as follows (time in minutes): (Table: see text). The data given above might be of value for the estimation of actual personal and time requirements in endoscopic units. PMID- 2316265 TI - [6th Working Group Meeting of the German Association for the Study of the Liver. Bonn, 26-27 January 1990. Abstracts]. PMID- 2316264 TI - [Carcinoid tumor of the esophagus. A rare differential diagnosis in submucosal esophageal tumor]. AB - In a 63-yr-old male endoscopy revealed an occlusive submucosal tumor in the upper esophagus. The surgically enucleated tumor was identified histologically and immunohistochemically as a carcinoid. The tumor had no endocrine activity. The localisation of these tumors in the esophagus is an extremely rare condition. PMID- 2316266 TI - [Clinical trends in 520 twin pregnancies in 22 years]. AB - In the last 22 years 520 twin pregnancies were seen at the Department of Obstetrics and Gynecology, University of Ulm. The material was analyzed retrospectively according to the 4 time periods 1965-1974, 1975-1980, 1981-1983, and 1984-1987. An equal-size group of singleton pregnancies was used as control. 1. By the 20th week the diagnosis had been established in 67% between 1984 and 1987 and 29% between 1975 and 1980. 2. A cervical cerclage was most commonly done between 1981 and 1983 (75%). The frequency decreased afterwards and a cerclage was only done in 18% in 1987. 3. Tocolytic agents were used in 7% between 1965 and 1974 and in two thirds of cases in the last years. 4. Hospital admission before delivery was most common between 1975 and 1980 (33%). In the last 7 years it was only half as common (15%). 5. There was no difference in the frequency of preeclampsia and eclampsia between singleton and twin pregnancies in the last years. 6. Maternal hemoglobin levels below 10% were more common in twin pregnancies than in the control group: Before delivery 11%, after delivery 22% in the twin pregnancies, compared with 6% and 4% in the singleton pregnancies. 7. There was no increase in the duration of pregnancy in the last 22 years. The difference between actual birth date and estimated date of delivery remained about the same in the 4 examined time periods: 21 days, 20 days, 21 days, 27 days. There was a slight increase in the frequency of delivery before the 37th week in twin pregnancies: 38%, 41%, 43%, 47%. PMID- 2316267 TI - [Prematurity and prenatal care]. AB - In regard of the constant rate of low birthweight infants in Federal Republic of Germany kinds and relevance of social factors within Low Birthweight are examined. Results of a study based on all births in Berlin (West) during the years 1982-1985 (n = 72201) are presented. It shows a constant rate of low birthweight infants also in Berlin (mean: 6.3%, excluding multiple births). Several social factors (legitimacy, nationality...) with varying intensity played a major role, especially if certain risk situations were cumulating. Since Prenatal Care has particular difficulties in reaching women at higher risks early and consequently, specific approaches of intervention derived from experiences in the US are suggested. PMID- 2316268 TI - [Personality-dependent anxiety reactions in primiparous patients]. AB - The emotional state of the gravida shortly before childbirth has a predictive value for her comportment during parturition. We evaluated, whether the concept of defensive coping with fear (repression vs. sensitization) contributed to a better identification of patients at risk. Both repression and sensitization are inadequate attempts of warding off fear, the difference being the interpretation of the triggering situation. We interviewed 101 primiparous women during routine pregnancy check-ups between the 34th and 40th week of pregnancy. The following instruments were applied: demographic data, repression-sensitization scale, scales concerning birth preparation and fear of birth, Spielberger's STAI-X and the Giessen scale of psychosomatic complaints. Three days post partum a scale concerning the experience of birth and the STAI-X were completed. Sensitizers had a tendency to admit fears more openly in the STAI-X and to experience birth as threatening. They complained about more psychosomatic symptoms than the repressor group in the Giessen scale. Non defensive-copers were found in-between. Sensitizers showed highest levels of fear of birth. No differences between repressors, non-defensive copers and sensitizers could be found concerning demographic data like birth complications (spontaneous delivery vs. cesarean section/forceps delivery). Neither did the groups show differences concerning the attendance of birth preparation courses. PMID- 2316269 TI - [Value of endogenous uterine contraction stress test by breast nipple stimulation]. AB - In a prospective study we performed a breast-stimulation-test (BST) in 136 patients. Sufficient contractions could be achieved in 89.7%. A hyperstimulation was seen in 5.8% of the patients. We could not find a false negative BST-result. The duration of the BST was significantly shorter compared to the OBT. The new noninvasive method was well accepted by patients and staff-members, leading to a new management of fetal surveillance in patients beyond 40 weeks of pregnancy. PMID- 2316270 TI - [Effect of co-medication with magnesium sulfate in beta-mimetic tocolysis on parameters of water-electrolyte balance]. AB - With 2 groups of 10 patients the influence of an additional therapy with 1 g magnesium sulfate/h during i.v. tocolysis with the betamimetic fenoterol (2 micrograms/min) upon parameters of water and electrolyte balance has been investigated. The whole of the magnesium administered during the 24 hours investigational period has been eliminated via the kidneys. Most probably due to a competition within the distal tubulus hypermagnesemia was associated with hypocalcemia and hypercalciuria, followed by a rise in parathyroid hormone. As PTH is able to compensate hypocalcemia not only by means of bone mobilisation but also by an increase in enteral Ca absorption, estimated losses of calcium are minimal. These may be neglected, as additional therapy with magnesium sulfate- besides the advantages yet known (cardioprotection, saving of betamimetic dosage, reduction of drug tolerance development)--reduces betamimetic induced water retention, thus significantly diminishing lung edema hazard during tocolytic therapy. PMID- 2316271 TI - [Course of pregnancy and labor following in vitro fertilization. A retrospective study of 246 deliveries]. AB - This record concerns the statistical registration and analysis of the courses and developments having taken place in 246 pregnancies and births after in-vitro fertilization. The cases were registered retrospectively, the degree of registration being 77.2% approximately; the scientific evaluation was carried out on the basis of the BPE 1987. It can be shown that there is an increased incidence of the EPH-gestosis, the clinically relevant placenta insufficiency syndrome, the intrauterine death of fetus, the abruptio placentae and prematurity. As predisposing factors must primarily be seen and discussed the ovarian hyperstimulation being--in most cases--connected with IVF and the higher age of the patients; it can be supposed that the method of fertilization in vitro itself is of minor importance. Its importance in the pathogenesis of abruptio placentae, however, cannot be exactly evaluated so far. The frequency of multiple pregnancies represents a special problem. Though the rate is lower in the examined group than in comparable--that is due to the limited number of collected oocytes--it should be aimed at a further lowering of multiple pregnancy rates. PMID- 2316272 TI - [Changes in left ventricular hemodynamics and contractility and significance of various reperfusion phase times in recurrent short duration ischemia in the human]. AB - The time courses of left ventricular systolic (LVSP) and enddiastolic (EDP) pressures as well as changes in peak dp/dtmax and peak dp/dtmin using high fidelity-tip catheters were studied in 35 out of 179 consecutive patients undergoing elective percutaneous transluminal angioplasty (PTCA) of the left anterior descending artery (LAD). Only patients with global and regional normal left-ventricular function and without collateral filling of the target vessel in the diagnostic angiograms were included. Occlusion time of the LAD was 50 and 60 s during each cycle. Reperfusion time between each vessel occlusion was 60 s in 15 patients and 180 s in 20 patients. During every ischemic period identical significant decreases of LVSP (p less than 0.005), peak dp/dtmax (p less than 0.001), and peak dp/dtmin (p less than 0.001) and significant increases of EDP (p less than 0.001) were documented. The maximum of hemodynamic changes in every patient was within the first 20 s after vessel occlusion. With a reperfusion period of 60 s LVSP and EDP did not return to basic level and the difference reached statistical significance (p less than 0.05) during the fourth occlusion. This could not be documented when the reperfusion period lasted 180 s. For clinical implications a reperfusion time of 180 s between consecutive repeated short periods of ischemia during PTCA could be recommended. PMID- 2316273 TI - [Comparison of the oxygen deficit and ischemia pain threshold in patients with silent and symptomatic myocardial exercise-induced ischemia]. AB - In 39 patients with angiographically documented coronary artery disease and silent or symptomatic myocardial ischemia under exertion it was investigated if there is a difference in forearm skeletal muscle ischemia and ischemic pain threshold. The degree of myocardial ischemia was determined by plethysmographically measured reactive hyperemia. In 12 asymptomatic and eight symptomatic patients maximal reactive hyperemia was induced by ischemic work in the forearm skeletal muscle. After termination of ischemia there was a significantly higher reactive hyperemia at 20, 90, and 180 s in the asymptomatic patients. Furthermore, nine asymptomatic and 10 symptomatic patients underwent symptom-limited ischemic work until weakness or pain developed. Under these conditions reactive hyperemia as a parameter of oxygen deficiency was higher in the asymptomatic patients. The difference was not statistically significant. There was, however, a significantly higher incidence of ischemic pain in the symptomatic patients. It can be concluded that patients with asymptomatic myocardial ischemia tolerate a higher oxygen deficit in the working forearm and have a higher pain threshold than patients with symptomatic ischemia. PMID- 2316274 TI - [Effect of the duration of reperfusion on metabolic recovery during unloading of the hypertrophic heart following induced heart arrest]. AB - The methods of cardioplegia used today are not always able to sufficiently protect the hypertrophied heart. The present study investigated if a recovery period of 30 min before the end of ECC improves metabolic recovery of the heart in comparison to a recovery period of 15 min before terminating extracorporeal circulation. A clinical study was performed of patients undergoing aortic valve replacement. In one group reperfusion was performed for 15 min and in the second group for 30 min before the conclusion of extracorporeal circulation. The concentration of high energy phosphates in the left ventricle was determined at the end of the ischemic period, after 15 min and after 30 min of reperfusion. The behavior of the myocardial metabolites of the two groups showed no differences. Creatinephosphate increased continuously in both groups, while adenosine triphosphate and the adenonucleotide pool did not change during the reperfusion period. From our results we conclude that under the conditions given in our study a recovery period of 15 min is sufficient for metabolic recovery and prolongation of reperfusion before termination of extracorporeal circulation do not improve metabolic recovery. PMID- 2316275 TI - [Spontaneous coronary artery dissection: a rare cause of myocardial infarct]. AB - The case of a 52-year-old female is presented who suffered from myocardial infarction with a prolonged course of symptoms. The angiographic examination revealed a spontaneous dissection of the right coronary artery without evidence for atherosclerotic coronary artery disease. Under medical treatment no further complications occurred. Control angiography showed a spontaneous improvement of the dissection. The characteristic clinical features of this case are compared with the literature data on angiographically visualized spontaneous coronary artery dissections. PMID- 2316276 TI - [Surgical treatment of Wolff-Parkinson-White syndrome--experiences with 87 surgically treated patients]. AB - Since January 1984, 87 patients (pts) (57 male, 30 female; age 3 to 64 years) with Wolff-Parkinson-White syndrome were operated upon. The indication for surgical treatment was documented recurrent, paroxysmal tachycardia refractory to medical treatment in 85 cases. Eleven pts (13%) had additional heart disease. 87 pts had a total of 103 accessory pathways (AP). AP was localized at the left free wall in 68% (70 AP), at the right free wall in 16% (16 AP), and localized septally in 17% (17 AP). Thirteen pts (15%) had multiple AP (10 pts had two and three pts had three AP). 87 AP were known preoperatively, 96 were localized intraoperatively, and seven were diagnosed during reoperation. Twenty-seven pts were left lateral AP were operated by the epicardial approach and 37 pts by the endocardial approach. Patients with right lateral AP were approached by an epicardial technique in six cases, and by a transmural technique in five. Cryotechnique was applied additionally in 85 pts. Twelve pts suffered recurrences, 11 were reoperated. 101 AP (98%) were dissected successfully, of which 13 (13%) were ablated during reoperation. All pts survived the initial operation. Two pts died after reoperation. One pt is pacemaker-dependent due to a persisting postoperative AV block. We conclude that surgical dissection of accessory pathways can now be offered as an alternative to the non-surgical treatment modes, with low risk and yielding a high success rate. PMID- 2316277 TI - [Indications for pacemaker therapy in ophthalmoplegia plus and Kearns-Sayre syndrome]. AB - Mitochondrial myopathies can affect the skeletal muscle, the central or peripheral nervous system, and they may be associated with chronic progressive external ophthalmoplegia (CPEO). In 7/29 patients with mitochondrial myopathies and CPEO a cardiac involvement (Kearns-Sayre syndrome) was found: incomplete right bundle branch block (n = 1), right bundle branch block (n = 1), left anterior fascicular block and right bundle branch block (n = 2), complete atrioventricular block (n = 3); congestive cardiac failure (ejection fraction 40%) (n = 2); 3/10 patients had prolonged infranodal conduction on His-bundle electrography (HV-interval 60 ms). The cardiac involvement in ophthalmoplegia plus is characterized by progressive impairment of fascicular conduction. The need for prophylactic pacemaker implantation appears to exist in patients with bifascicular block and prolonged His-ventricle conduction. PMID- 2316278 TI - [Infectious endocarditis following orthotopic heart transplantation]. AB - Infection remains a major problem in the early phase after heart transplantation. Immunosuppressive therapy is the most important predisposing factor. It may also reactivate preexisting latent endogenous infections. Unspecific symptoms and a chronic clinical course, as described in this report, may suggest infective endocarditis of the cardiac allograft. From this case, we do not suggest a general antibiotic prophylaxis for heart transplant recipients; however, special precaution should be considered in heart transplant patients with a history of endocarditis. PMID- 2316279 TI - [Doppler echocardiography evaluation of left ventricular function in intra-aortic balloon counterpulsation]. AB - Doppler-echocardiographic measurement of transaortic and mitral flow allows an assessment of systolic and diastolic left ventricular performance. To evaluate the hemodynamic effects of intra-aortic balloon counterpulsation (IABP) 10 patients were examined during IABP after myocardial infarction or cardiothoracic surgery. Doppler echocardiographic transaortic (VAo), early (VE) and late (VA) transmitral flow velocities, transaortic velocity time integral (VTIAo), acceleration and deceleration intervals and rates were obtained. The IABP augmentation was changed from 1:1, 1:2 to 1:4 causing no notable change in invasively measured arterial pressures (p greater than 0.05). With constant heart rate the VE/VA ratio was similar in 1:2 and 1:1 mode (1.44 +/- 0.42 vs 1.47 +/- 0.27; p greater than 0.2), whereas VAo and VTIAo were increased (p less than 0.01). A beat-to-beat analysis during 1:2 mode confirmed an increase in VAo (84.1 +/- 13.5 vs 98.3 +/- 16.5 cm/s; p less than 0.01) and VTIAo after the augmenting balloon inflation, but did not confirm any concomitant effect on diastolic transmitral parameters; acceleration and deceleration intervals were not changed. Thus, Doppler-echocardiography was able to detect an increase in transaortic flow during IABP augmentation by beat-to-beat analysis. The increase in VTIAo indicates an elevated cardiac output. A similar instantaneous effect on the diastolic transmitral flow could not be identified. PMID- 2316280 TI - Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2. AB - Vector-directed lymphokine expression represents a novel approach to the attenuation of live recombinant viruses which might be used as vaccines. Expression of interleukin-2 (IL-2) by recombinant vaccinia virus has been shown to significantly attenuate virus virulence in rodent species without diminishing immunogenicity. Skin lesion formation and immunogenicity of vaccinia/IL-2 recombinants in three species of primates was examined. IL-2 expression was associated with a 15-fold reduction in the area of induration after intradermal inoculation of recombinant viruses in patas monkeys. Wild type and a control vaccinia recombinant produced large (greater than 5000 mm2) skin ulcers in this species, but the IL-2 expressing recombinant produced no ulceration. Production of antibodies to vaccinia virus and to influenza A virus haemagglutinin expressed by recombinant vectors was examined in rhesus and squirrel monkeys. IL-2 expression accelerated the resolution of skin lesions in rhesus but not squirrel monkeys. Despite this, antibody production was equivalent in the presence or absence of IL-2. IL-2 expression can greatly reduce the skin lesions formed by live recombinant vaccinia vectors in primates, indicating significant attenuation, without reducing the immunogenicity of the vaccine. PMID- 2316281 TI - A new vaccine against tick-borne encephalitis: initial trial in man including a dose-response study. AB - A new vaccine against tick-borne encephalitis was investigated in 56 healthy volunteers randomized for five different doses of antigen in a comparative group trial. Good tolerability and high immunogenicity were found using three different antibody test systems. The dose response study revealed that there was a strong relationship between the amount of antigen administered and the antibody response over the range of 0.03-3.0 micrograms antigen per dose. PMID- 2316282 TI - AIDS vaccine research in the UK. AB - The UK Medical Research Council initiated a Directed Programme, aimed at developing vaccines for prevention and drugs for treatment of HIV infection and AIDS, in April 1987. This is a single collaborative research programme encompassing work in about 100 UK laboratories together with a small number in Europe and the USA. The third annual workshop for the programme, held at the University of Sheffield in September 1989, which brought together nearly 400 scientists, technical staff and students, as well as representatives of other national AIDS research programmes, showed that the Directed Programme is now well established and productive, making important contributions to the worldwide effort to control AIDS. PMID- 2316283 TI - Purified chick-embryo-cell (PCEC) rabies vaccine: its potency performance in different test systems and in humans. AB - The potency of purified chick embryo cell rabies vaccine Rabipur was evaluated by four different in vivo test systems: (1) NIH test with homologous strain LEP challenge; (2) intramuscular challenge of vaccinated laboratory animals; (3) postexposure vaccine treatment trials in laboratory animals; and (4) antibody induction tests in laboratory animals. These different test systems were compared with the Standard NIH test and an in vitro test, the modified ABT. Each of the four in vivo methods chosen demonstrated potency values superior to that of the Standard NIH test in which challenge was with CVS strain. Potency relations were: Standard NIH test versus alternative methods versus modified ABT 1.0-2.2-1.85 respectively. There was good correlation between alternative in vivo methods and the ABT. In addition examples of antibody induction in man following administration of various postexposure treatment regimens are presented which lead to the conclusion that postexposure vaccination method and composition of the study group play a more important role in achieving optimum treatment results than vaccine potency, provided that it corresponds to WHO requirements (minimum 2.5 IU per dose). PMID- 2316284 TI - Enhancement of antibody responses to influenza B virus haemagglutinin by use of a new adjuvant formulation. AB - Mice and guinea pigs were immunized with the haemagglutinin (HA) of influenza B USSR/100 virus, either in Syntex Adjuvant Formulation-1 (SAF-1) or in saline. Antibody titres were determined by ELISA, haemagglutination inhibition and virus neutralization. Animals immunized with HA in SAF-1 had significantly higher antibody titres than did animals immunized with HA in saline. Both 3-week-old and 13 1/2-month-old mice had greater and more uniform antibody responses to HA in SAF-1 than to HA in saline. PMID- 2316285 TI - Laboratory properties of cold-adapted influenza B live vaccine strains developed in the US and USSR, and their B/Ann Arbor/1/86 cold-adapted reassortant vaccine candidates. AB - The adaptation of two influenza B strains (B/Leningrad/14/55 and B/Ann Arbor/1/66) to replication at 25 degrees C is described. Comparison of the two viruses indicates that both also exhibit temperature sensitive phenotypes, although that of the virus B/Leningrad/14/55 is less pronounced. When inoculated into ferrets both viruses replicate well in the trachea, but only the B/Leningrad/14/55 cold-adapted virus replicates in the lungs. This virus exhibited a moderate level of attenuation in the animals, in contrast to the B/Ann Arbor/1/66 cold-adapted virus, which was fully attenuated. Reassortant viruses deriving the surface antigens of the contemporary wild type virus B/Ann Arbor/1/86 and most or all of their other genes, from one or other cold-adapted parent, were virtually indistinguishable from their respective cold-adapted parents. The B/Leningrad/14/55 reassortant was slightly more attenuated than its cold-adapted parent in ferrets. These studies extend knowledge of the properties of viruses used to prepare experimental live influenza B human vaccines. PMID- 2316286 TI - Occurrence of peroxisomal membrane proteins in methylotrophic yeasts grown under different conditions. AB - We have studied the substructure and polypeptide composition of the peroxisomal membranes in two methylotrophic yeasts in relation to different growth conditions. The results obtained indicated that no significant ultrastructural differences existed between the membranes of variously grown cells. The presence of specific peroxisomal membrane proteins (PMPs) was studied biochemically. On sodium dodecyl sulphate-polyacrylamide gels of purified microbody membranes isolated from methanol-grown Hansenula polymorpha, prominent protein bands were observed at 22, 31, 35, 42, 49 and 51 kD. These proteins were also present when the cells were grown in media containing ethanol and/or ethylamine. Apart from these, several other PMPs were specifically induced under these conditions, namely 24, 29, 37 and 62 kD proteins. The polypeptide composition of peroxisomal membranes from H. polymorpha was compared with that of another methylotroph, Candida biodinii. In the latter organism a specific PMP with a molecular weight of 23 kD was induced during growth on D-alanine instead of ammonium sulphate as the nitrogen source. PMID- 2316287 TI - [Surgical treatment of bronchial carcinoid]. AB - 84 patients with bronchial carcinoid tumors were analysed on during of 28 years. 26 of them were detected by radiography and 58 by symptoms. The bronchoscopy with biopsy is the most important diagnostic procedure. The preoperative histological or cytological diagnosis was correct in 25 cases. The suspicion was given only in 39 patients. The surgical therapy was carried out in all cases with conventional resection of lung as well as parenchyma preserving methods. We used atypical or typical segmental lung resections, bronchotomy with direct suture, sleeve or wedge resection of the bronchus and fenestration of bronchus with closure of the window with free skin graft. The prognosis after surgical treatment is very good. The 5-year-survival was 89%. PMID- 2316288 TI - [Correlation of tumor site and tumor volume in radical surgery of cancer of the peripapillary area]. AB - In a group of 52 partial duodenopancreatectomies (34 cancers of the head of the pancreas, 14 cancers of the papilla and 4 cancers of the common bile duct) the dependence of tumour volume and tumour localisation on carcinomatous lymph node involvement, infiltration of surrounding tissues, infiltration of great visceral vessels and not radical resection was determined. The analysis demonstrates that there is significant difference in volume between radically treated carcinomas of the common bile duct, the papilla of Vater and the head of the pancreas with mean volumes of 463:1,851:11,835 mm3 or 1:4:26! Furthermore the investigation shows that for every analysed parameter median volume is larger for positive observations than for negative ones: lymph node involvement 10,606:6,459 mm3, infiltration of surrounding tissues 10,444:6,703 mm3, infiltration of great visceral vessels 14,923:7,144 mm3, not radical resection 18,130:5,343 mm3. From these results it is concluded, that early stages of periampullary carcinomas with a good chance for cure are only present in radically treated cancers of the papilla and the common bile duct. In cancers of the head of the pancreas the significant larger primary cancers and the more advanced staging results in a dismal prognosis. PMID- 2316289 TI - Papillary carcinoma of thyroglossal duct cyst. A case report. PMID- 2316290 TI - [Urethral wall pulsation in pregnant patients, continent and stress incontinent females]. AB - The amplitudes of urethral vascular pulsations in pregnant women, continent and urinary stress incontinent women were compared with each other. Significant differences have been found in the chi 2-Test. In pregnant women the mean pulsation amplitude was 1.81 kPa, in continent women it was 1.13 kPa and in urinary stress incontinent women 0.46 kPa. Low or missing urethral vascular phenomena seem to be connected with urinary stress incontinence. That is why the amplitude of urethral pulsation should be taken into consideration in the urodynamic investigation of urinary stress incontinence. PMID- 2316291 TI - [Colposcopic, cyto- and histologic signs of papilloma virus infection in precancerous and early stages of cervix cancer]. AB - Basis of present study are examinations in 100 women with colposcopic and/or cytologic abnormalities suspect of preinvasive or early invasive carcinoma of the uterine cervix. We found 76 colposcopic abnormal findings in 100 women examined. In 36 women there was a colposcopic suspicion on a papilloma virus infection, in 32 cases combined with abnormal colposcopic findings. All 100 patients had cytologic smears group III and/or IV according to Papanicolaou. In 71 women cytologic signs of a papilloma virus infection was detected in the cervical smears. We found histologic signs of a papilloma virus infection in 69 cases in the specimen of biopsy, conization or hysterectomy (5 times condylomata acuminata, 53 times flat condylomata and 11 times inverted condylomata). Preinvasive respectively invasive and papillomavirus caused lesions of the cervix are coexisting in 59 cases. Our examination demonstrates that also in GDR in about 70 per cent of the precancerous or invasive cervical lesions signs of an infection with human papilloma viruses are present histologically and/or cytologically. PMID- 2316292 TI - [An ethics discussion in gynecology and obstetrics]. PMID- 2316293 TI - [HELLP syndrome in the 23d week of pregnancy. A case report and literature discussion]. AB - A case report is given on a 24 years old primipara who developed a progredient HELLP-syndrome (H = hemolysis, EL = elevated liver enzymes, LP = low platelet counts) in the 23rd week of gestation two days after first diagnosis of pregnancy induced hypertension. As the situation became increasingly critical, the pregnancy had to be terminated in the 23rd week of gestation by sectio parva. To our knowledge the development of a HELLP-syndrome at this early gestational age has not yet been described. PMID- 2316294 TI - Heterotopic pregnancy. The first case with an IUD in situ. AB - The first reported case of simultaneous tubal and intrauterine pregnancy in a women with an IUD in situ is presented. The incidence of combined pregnancies is estimated as 1 to 2 pr. 10,000 gestations. The risk of IUD using women for becoming combined tubal and intrauterine pregnant is calculated as 1:6,000,000 women years of use. PMID- 2316295 TI - [Prenatal diagnosis of triploidy (69,XXX) in the 29th week of pregnancy with fetal death in the 37th week of pregnancy]. AB - A case report is given on a pregnancy in the 29th week of gestation. Sonographic control showed extensive oligohydramnions, a size date discrepancy was noted, and there was no spontaneous movement of the fetus. An amniocentesis revealed triploidy as the cause. The clinical, sonographic, and hormonal data as well as the autopsy findings are discussed. PMID- 2316296 TI - [Adjuvant therapy also in node-negative breast cancer?]. PMID- 2316297 TI - [Indications for roentgenologic diagnosis of the colon in gynecology]. AB - X-ray barium-enema examination of the colon recently is an established method in gynecology performed as differential or spreading diagnosis. In 276 patients the results of 291 barium-enema examinations have been analysed retrospectively. The radiographic findings correlate 279 times with the intraoperative and histologic diagnoses (165 correct nonpathologic and 114 correct pathologic). On the basis of the obtained correct and false diagnoses, common indications for using irrigoscopy in gynecology have been suggested. In this context, abdominal and/or vaginal sonography as well as sigmoidoscopy are suitable methods which should be applicated compulsorily before radiologic examination of the colon in women suffering from gynecologic diseases. PMID- 2316298 TI - [Prognostic significance of the length of the uterus, depth of infiltration and grading of endometrium cancer]. AB - 84 patients who underwent operation for adenocarcinoma of the endometrium stage I have been investigated with regard to morphometric and histologic prognostic factors. Measuring the maximal depth of infiltration of the carcinoma in relation to the thickness of the uterine wall, tumor grading and carcinomatous lymphangiosis are of dominant value. Measuring the length of the uterine cavity is without significance. Patients with a short length had more often recurrences than patients with a longer one. PMID- 2316299 TI - [Follow-up in cervix intra-epithelial neoplasia and condylomatous lesions of the uterine cervix]. AB - 77 women with colposcopic and/or cytologic suspicious signs had been followed up 6 to 46 months. In 23 (44 per cent) out of 52 women with CIN we could observe progredience, in 19 (37 per cent) cases dysplasias and carcinoma in situ remained unchanged and in 10 (19 per cent) there was a regression. From 18 benign condylomatous lesions 8 were regredient and sones were progredient. Only in 1 out of 7 cases with benign lesions without papilloma virus infection a CIN II developed. Follow up of pregnant women demonstrated twofold more regredient findings compared with nonpregnant women. Follow up over a period of several years with colposcopic, cytologic and histologic examination in young women with CIn and childwish is possible without risk if definite management will be secured. PMID- 2316300 TI - Nutrition and cardiovascular risk in Hungary. PMID- 2316301 TI - The four diastoles. A cardiac-cycle model. PMID- 2316302 TI - Nutrition and cardiovascular risk: the Hungarian experience. PMID- 2316303 TI - Effect of serum from spontaneously hypertensive rats on 86Rb washout in cultured vascular smooth muscle cells. AB - In addition to the known genetic abnormalities affecting the membrane permeability of vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR), serum humoral factors may also play some role in the alteration of permeability of VSMC and possibly contribute to the pathogenesis of hypertension in SHR. To test this hypothesis, the passive K permeability described as the washout rate constant (Ke) was measured based on 86Rb washout from cultured VMC in response to serum from SHR, Wistar-Kyoto rats (WKY), and Wistar rats (W). Serum from the three rat strains produced a substantial increase in the Ke of 86Rb washout from 9.6 +/- 1.7 for the control (C) of 17.3 +/- 2.0 for SHR. 15.3 +/- 0.9 for WKY, and 16.0 +/- 2.4 for W (x 10(-3)/min) (p less than 0.001 comparing C with SHR, W and p less than 0.01 comparing C with WKY respectively). However, comparison of the Ke of 86Rb washout among the three rats strains revealed no significant differences. It is concluded that serum increased passive K permeability of VSMC in culture. However, the data do not support the suggestion that some unknown humoral factors in the serum from SHR are involved in the abnormal alterations of membrane permeability to cations and thus contributing to the pathogenesis of hypertension in the SHR. PMID- 2316304 TI - Evaluation of the safety and efficacy of amrinone in chronic obstructive lung disease with cor pulmonale. AB - In a pilot study the effect of a bolus dose of amrinone intravenously (IV), 0.5 or 1 mg/kg body weight, in 10 patients with chronic obstructive lung disease and cor pulmonale was evaluated. We found that the higher dose of 1.0 mg/kg IV significantly (P less than 0.05) decreased the mean pulmonary artery pressure and pulmonary wedge pressure without significant changes in cardiac output, in systemic blood pressure or in arterial blood gas values. No adverse effects were recorded in any of the patients. PMID- 2316305 TI - Ochronosis and alkaptonuria: report of a new case with calcified aortic valve stenosis. AB - A patient with calcified aortic valve disease secondary to ochronosis and alkaptonuria is presented. Urgent aortic valve replacement was necessary. The cardiovascular complications of this disease are reviewed. PMID- 2316306 TI - A polyclonal antiserum against chromogranin A and B--a new sensitive marker for neuroendocrine tumours. AB - Chromogranins A, B, and C, proteins that are co-stored and co-released with peptides and amines, have been identified in a variety of neuroendocrine tissues, both normal and neoplastic. We examined the secretion of chromogranin A and chromogranin A + B by hormone-producing tumours in patients with endocrine pancreatic tumours, carcinoid tumours, pheochromocytomas, and small cell lung cancer. The radioimmunoassay determining the plasma concentrations of chromogranin A + B showed a greater sensitivity than that determining chromogranin A alone. All patients with endocrine pancreatic tumours, carcinoids, and pheochromocytomas had increased levels of chromogranin A + B, whereas a small number of the patients (5/18 with endocrine pancreatic tumours and 1/3 with pheochromocytomas) had normal levels of chromogranin A. Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C. We have demonstrated that a polyclonal antiserum against a mixture of chromogranin A and B might be a more sensitive marker than chromogranin A alone for diagnosing neuroendocrine tumours. This is not surprising, since both chromogranins are widely distributed in neuroendocrine cells. PMID- 2316307 TI - Metabolic fuel and amino acid transport into the brain in experimental hypothyroidism. AB - The effect of hypothyroidism in the adult rat on blood-brain barrier and muscle transport of hexoses, neutral amino acids, basic amino acids, monocarboxylic acids, and ketone bodies was examined using single arterial injection-tissue sampling technique. The cerebral blood flow and brain extraction of 3H2O (internal reference substance) was not altered in 3-month-old hypothyroid rats maintained on methimazole, 0.025% in the drinking water, for 7 weeks. The brain uptake index of D-beta-hydroxybutyrate was significantly reduced in hypothyroid rats (2.4 +/- 0.3 vs 4.6 +/- 0.6% p less than 0.001). Hypothyroid rats given thyroid hormone replacement therapy had normal brain uptake of D-beta hydroxybutyrate (4.4 +/- 0.8%). The brain uptake index of butyrate was also significantly reduced in hypothyroid rats (39.3 +/- 2.1 vs 47.2 +/- 0.74%, p less than 0.001). The brain uptake index of other test substances and muscle uptake of nutrients examined were not altered in hypothyroid rats. These studies indicate that of the four transport systems examined in two tissues, the blood-brain barrier monocarboxylic acid transport system is most susceptible to the hypothyroidism-induced changes. PMID- 2316308 TI - The effect of fasting on thyroidal T4-5' monodeiodinating activity in mice. AB - Complete fasting induces a significant decrease of serum T3 and a fall in TSH in rodents and man. To evaluate the effect of starvation on thyroidal T4 5'monodeiodinating activity, in vitro conversion of T4 to T3 by thyroid and liver homogenate from one to three days fasted mice was compared with homogenates from control mice on animal chow. 5'monodeiodinating activity was significantly lower in thyroid homogenates of fasted mice than in those of chow-fed control [100 +/- 5.0 and 92 +/- 5.0 pmol T3.(mg protein)-1.h-1 at 48 and 72 h fasting, respectively, vs 132 +/- 5.0 pmol T3.(mg protein)-1.h-1 of fed control, p less than 0.01]. A similar decrease in thyroidal 5'monodeiodinating activity was seen in the liver. The decrease in thyroidal 5'monodeiodinating activity induced by fasting was not reversed by the supplementation of homogenates with the thiol protecting agent, dithiothreitol (0.2-4.0 mmol/l). Physiological replacement of T4, 0.58 nmol.(100 g)-1.day-1, did not alter the effect of starvation in either the thyroid or liver. TSH (0.02 IU/day) injection, on the other hand, stimulated 5'monodeiodinating activity in homogenates of thyroids from 3-days fasted mice which was no different from TSH-treated fed control. It is postulated that starvation-induced decrease in thyroidal T4 to T3 converting activity may play a role, together with decreased hepatic 5'monodeiodinating activity, in fasting induced low serum T3 in mice. PMID- 2316309 TI - Tissue-specific differences in the compartmentalization of rat nuclear triiodothyronine receptors. AB - In addition to the recognized rat liver nuclear T3 receptor extractable with hypertonic salt, recent studies have described nucleoplasmic receptors extractable with isotonic KCl and salt-resistant receptors localized to the nuclear matrix. A method was developed for the determination of intra-nuclear receptor distribution in small samples of nuclei dispersed within glass wool matrices. After in vitro labelling with 6 nmol/l [125I]T3, dispersed nuclei were sequentially extracted with 0.15 mol/l KCl (yielding nucleoplasmic receptors), 0.4 mol/l KCl. and 2 mol/l KCl (the latter two concentrations yielding hypertonic salt-extractable receptors). The salt-resistant receptors were retained within the glass wool columns. The intra-nuclear distribution of in vivo labelled receptors was very similar to that obtained by in vitro labelling. The equilibrium association constants for L-T3 binding among the receptor pools ranged from 0.6 X 10(9) to 1.0 X 10(9) l/mol. The distribution of total nuclear receptors within each nuclear compartment was (percentage of nucleoplasmic, hypertonic salt-extractable, and salt-resistant receptors): Cerebrum: 23.6, 52.2, 24.2; Liver: 25.2, 57.2, 17.5; Kidney: 45.9, 33.5, 20.6; Testis: 65.5, 14.7, 19.7; and Spleen: 66.7, 18.7, 14.6. The rank order of percentage of hypertonic salt-extractable receptors approximates the rank order of thyroid hormone responsiveness by traditional criteria. The inverse is true for the percentage of nucleoplasmic receptors. The percentage of salt-resistant receptors was very similar in all of the tissues. PMID- 2316310 TI - Effects of parathyroid hormone fragments on the growth of murine mandibular condylar cartilage in vitro. AB - The present study showed that the fragment hPTH (1-34) is mitogenic in organ cultures of neonatal mandibular condylar cartilage, and even more so in late fetal condyles. Three fragments of hPTH were used to clarify which part of the molecule possesses a mitogenic effect alike that of the native hormone: hPTH (1 34), (28-48) and (53-84). [3H]thymidine incorporation into trichloracetic acid insoluble material and quantitative autoradiography were employed in a serum-free medium to assess the effects of these fragments while light and electron microscopy studies served for morphological evaluations. It became evident that the fragment hPTH (1-34) enhanced the incorporation of [3H]thymidine, a fact that could be noted only in serum-free medium. The putative target cells for the effects of hPTH (1-34) were the chondroporogenitor cells which also appeared to have experienced a blockage in their differentiation into chondroblasts. Ultrastructurally, the latter cells responded in the formation of adherent profiles of plasma membranes, whereas the differentiated zone of the cartilage reduced its size. Using serum-free medium, hPTH (1-34) also brought about an inhibition in alkaline phosphatase activity, a fact that was not encountered in medium containing serum. By contrast, hPTH (28-48) had no mitogenic effect, although treated specimens revealed morphological changes in the chondroprogenitor cell zone along with an enhancement of cartilage cells hypertrophy. No significant effects on either mitogenecity or morphology could be noted in hPTH (53-84)-treated cultures. PMID- 2316311 TI - Peripheral blood T cell activation after radioiodine treatment for Graves' disease. AB - Radioiodine therapy for Graves' thyrotoxicosis produces a rise in thyroid autoantibodies in the first three months after treatment, but little is known of its effects on T cells. We have therefore followed the changes in T cell subsets in sequential samples from 23 patients with Graves' disease treated with radioiodine, using dual-colour flow cytometry. In the first month after treatment there was a significant rise in activated T cells, identified by the markers HLA DR (la) and CDw26/Ta1 (p less than 0.025 in both cases). CD45RO-positive T cells, which are the primed population containing memory cells, also increased (p less than 0.025), but there was no change in CD45R-positive, resting T cells or in the CD4 to CD8 (helper to cytotoxic/suppressor) ratio. Vicia villosa-binding T cells, containing the contrasuppressor population, showed a more variable response, but the trend was to an overall increase from pre-treatment values (p less than 0.025). The changes did not appear to be related to antithyroid drug treatment, since they were seen irrespective of whether patients continued such therapy. These results suggest that T cell activation and enhanced contrasuppressor activity may in part be responsible for the rise in autoantibodies after radioiodine. The T cell changes could also contribute to the worsening of ophthalmopathy seen in some radioiodine-treated patients. PMID- 2316312 TI - Characterization of dimeric forms of human pituitary growth hormone by bioassay, radioreceptor assay, and radioimmunoassay. AB - Seven highly purified dimeric forms of human pituitary growth hormone, composed of the monomeric forms 20 K hGH, 22 K hGH and 24 K hGH linked together by noncovalent or covalent bonds, have been characterized by an in vitro bioassay (the Nb2 assay), a radioreceptor assay and a radioimmunoassay. Considerable differences in the ability to displace labelled recombinant hGH were observed in the radioreceptor assay. The seven dimeric forms varied over a range between 22 K hGH (most effective) and 20 K hGH. The three covalently-linked dimeric forms had nearly identical affinity constants. The mitogenic action of all but one of the hGH dimers in the Nb2 assay was in the same mutual order as the receptor binding activity in the radioreceptor assay. In the RIA, all dose-response curves were parallel except for those obtained with 20 K hGH and with the dimeric form (20 K 20 K)hGH. In this assay, dimeric variants of the constituents 22 K hGH and 24 K hGH were approximately twice as active as 22 K hGH on a molar basis, suggesting about the same affinity between the antibodies and each of the monomeric forms. Determination of the amino acid compositions of the dimeric forms provided support for their content of monomeric constituents as established earlier by electrophoretic analysis. PMID- 2316313 TI - Effect of amiodarone on non-deiodinative pathway of thyroid hormone metabolism. AB - Amiodarone, an iodine containing anti-arrhythmic drug, causes a significant decrease in molar ratio of daily production rates of T3 and T4 from 0.75 in controls to 0.36 in amiodarone-treated rabbits. A model was constructed from the above data which showed that metabolism of T4 via non-deiodinative pathways (e.g. tetraiodothyroacetic acid and/or conjugates) increased from 29% in untreated controls to 66% in amiodarone-treated rabbits. In this study, we have examined the metabolic clearance rate of tetraiodothyroacetic acid in rabbits given amiodarone (20 mg.kg-1.day-1 ip for 3 weeks) or saline (controls). Serum amiodarone and desethylamiodarone levels under the above experimental conditions were 0.20 +/- 0.067 and 0.17 +/- 0.058 mg/l, respectively, which were in the near therapeutic range observed in humans. Control and amiodarone-treated rabbits were administered [125I]-tetraiodothyroacetic acid (10 muCi/rabbit) iv and blood was collected at 0.5, 1, 2, 4, 6, 10, 32 and 48 h. Serum tetraiodothyroacetic acid radioactivity was determined by trichloroacetic acid precipitation and ethanol extraction and metabolic clearance rates were calculated from the area under the curve of computer fits to tetraiodothyroacetic acid radioactivity data. Amiodarone treatment decreased metabolic clearance rates significantly from 0.107 +/- 0.008 in controls to 0.074 +/- 0.009 l/day in amiodarone-treated rabbits (p less than 0.05). However, when expressed per unit body weight (1.day-1.kg-1), the metabolic clearance rates were not significantly different between the controls and amiodarone-treated rabbits. The terminal serum elimination half-life in the two groups were similar (32.0 +/- 6.7 h in controls vs 49.2 +/- 12.4 h in amiodarone-treated).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316315 TI - Isolation of several fractions from human serum, inhibiting rabbit cartilage metabolism in vitro. AB - In contrast to the well characterized serum stimulators of cartilage metabolism, information is scarce on the nature of circulating inhibitors. Human serum was fractionated by molecular sieving chromatography on Sephadex G-200, G-75, G-50 and Biogel P-4 gels. Six fractions with molecular weights of 150, 45, 30, 16, 9 and 1.2 kD inhibited [35S]sulphate incorporation into rabbit cartilage segments. All fractions but the smallest one exhibited their inhibitory effect only in the serum-stimulated cartilage. The 1.2 kD fraction impaired [35S]sulphate and [3H]methyl-thymidine incorporation into the cartilage segments in both stimulated and basal conditions. A seventh inhibitory fraction corresponded to the serum salt peak. PMID- 2316314 TI - Parlodel LAR in the treatment of macroprolactinomas. AB - Eight patients with macroprolactinomas were treated with a long-acting injectable form of bromocriptine, depot-bromocriptine (Parlodel LAR). With the exception of one male patient who had partial and short-lasting suppression of PRL levels after two injections and who underwent a second adenomectomy, the patients were given Parlodel LAR injections at 28-day intervals for six months. In all patients, there was a significant fall in serum PRL levels after the first injection. PRL secretion was suppressed to within the normal range in 3 of 7 patients on long-term treatment. PRL was consistently within the normal range in 2 patients from the sixth week and in one, from the 14th week onwards. In the other 4 of 7 patients, a marked suppression of PRL secretion, resumption of menses, and normal libido and potency were recorded. In 3 of 8 patients, no adverse effects were noted. Two patients reported short-lasting nausea, one vomiting, one constipation and in 2 patients, orthostatic dizziness occurred after the first injection. Subsequent injections, however, were well tolerated systematically and locally. Five patients had CT scan evidence of tumour shrinkage. A very large tumour virtually disappeared after the first injection of 50 mg depot-bromocriptine in one patient. The decrease of serum PRL secretion within the first 12 hours after injection did not predict normalization of serum PRL levels during long-term treatment, whereas the fall of serum PRL levels to below 5% of the basal values within the first months of treatment could be a good indicator for the final outcome. PMID- 2316317 TI - [Proceedings of the 52d general meeting of the Japan Hematologic Society. Tokyo, 29-31 March 1990. Abstracts]. PMID- 2316316 TI - Postpartum thyroid dysfunction in Bangkok: a geographical variation in the prevalence. AB - To determine the prevalence of thyroid dysfunction in Thai postpartum women, we evaluated thyroid function and thyroid autoantibodies in 812 consecutive unselected women at 1.5 months post partum. At 3.5 months post partum 570 women without previous thyroid abnormality returned for a second set of thyroid function test. The prevalence of thyroid dysfunction was 1.1%, which was less than that reported from other countries. Various types of postpartum thyroid dysfunction, namely, transient thyrotoxicosis followed by transient hypothyroidism, transient thyrotoxicosis or hypothyroidism occurring alone or permanent hypothyroidism were encountered. Eight out of 9 patients with thyroid dysfunction had thyroid autoantibodies. Fine needle aspiration biopsy of the thyroid was done in 4 patients and all showed lymphocytic thyroiditis. Even though Bangkok is an iodine surfeit area, iodine intake is relatively lower than in other areas where the prevalence of postpartum thyroid dysfunction is much higher. The discrepancy in geographic prevalence of postpartum thyroid dysfunction may result from the interaction of immunogenetic heterogeneity of different ethnic background, environmental iodine intake, and other unidentified environmental factors. PMID- 2316318 TI - Explore professional opportunities as a certified registered nurse anesthetist. PMID- 2316319 TI - Preoxygenation of patients for coronary artery bypass grafting: vital capacity versus tidal breathing. AB - Arterial oxygenation, as measured by serial arterial blood gases (ABGs) and in vivo polarographic PaO2 during the rapid sequence induction of general endotracheal anesthesia, was evaluated in 20 ASA physical class IV subjects undergoing elective coronary artery bypass grafting (CABG). Subjects received a narcotic premedication 30-60 minutes prior to arrival in the operating room. Subjects in Group I (n = 10) were preoxygenated with 3 minutes of tidal breathing, while Group II (n = 10) subjects took four vital capacity breaths (VCB) within 30 seconds. Manual ventilation was withheld after the period of preoxygenation (the mean duration of apnea was 121.25 seconds). The mean PaO2 rose from 69.40 mmHg to 323.80 mmHg after preoxygenation in Group I and from 73.70 mmHg to 359.10 mmHg in Group II. After tracheal intubation, the mean PaO2 fell to 275.70 mmHg in Group I compared with 277.20 mmHg in Group II. There was no significant difference (p greater than 0.05) between the two methods of preoxygenation in their ability to increase arterial oxygen. In conclusion, vital capacity breathing is as effective as 3 minutes of tidal breathing in elevating the PaO2 in subjects with significant coronary artery disease prior to a rapid sequence induction. PMID- 2316320 TI - AANA Journal course: new technologies in anesthesia: update for nurse anesthetists--the computer-generated anesthesia record. AB - This lesson will introduce the anesthetist to computerized anesthesia record keepers, their history, development and current technology. It will identify some of the outstanding advantages and disadvantages of computerized record keepers from both clinical and legal standpoints. Computerized record keepers may not assume charting duties during all anesthetics administered in the United States but they do offer many advantages, especially during difficult cases. As their development continues, they may relieve the anesthetist of some repetitive and distracting tasks while providing clinically useful information and analysis. PMID- 2316321 TI - Development of the current certification examination. PMID- 2316322 TI - Hospital privileges. PMID- 2316323 TI - Herpetic whitlow: an occupational hazard. AB - Herpetic whitlow is a herpes infection of the digits of the hand, first described in 1909, caused by either herpes simplex virus type 1 or type 2. It was not until 1959 that herpetic whitlow was reported to occur in health care professionals. Nurse anesthetists are among the many health care professionals considered to be at high risk for acquiring herpetic whitlow, making it an occupational, but preventable, disease. After an initial infection, the virus invades the nerve tissue supplying the affected area, thus creating a reservoir for the virus to remain latent until reactivated. The recurrence of herpetic whitlow suggests that the infection persists for life. Pain, tingling and burning of the distal phalanx are the initial symptoms. Swelling and vesicles on an erythematous base follow. The infection is self-limiting, usually resolving in about three weeks. Primary infections are very inflammatory and persistent. Diagnosis can be made clinically and confirmed by many laboratory tests. Early recognition is most important, and treatment is symptomatic. The drug acyclovir has proven to be an effective chemotherapeutic agent for suppressive therapy. PMID- 2316324 TI - [Two atavistic characteristics of the laryngeal skeleton]. AB - In the analysis of laryngeal anomalies in 30 selected phoniatric patients by CT examination, 2 atavisms of the laryngeal skeleton were found. The ventral enclosure of the thyroid cartilage by the hyoid bone presents an inhibition malformation of the laryngeal skeleton with essential reduced vocal ability. The posterior junction between the cornu majus ossis hyoidei and the cornu superius cartilaginis thyroideae is marked by the direct contact of these cornua lacking the ligamentum thyrohyoideum laterale. Both anomalies are characterized by the persistence of the close relation between the hyoid bone and the thyroid cartilage, which normally exists phylogenetically as well as ontogenetically. That could be shown by anatomical sections performed on 4 human newborns in the horizontal plane. PMID- 2316325 TI - A simplified method of casting the macroscopic airways of lungs. AB - A technique for preparing casts of the macroscopic airways of mammalian lungs, which is both simplified and inexpensive in comparison with previous techniques, is described. The models are accurate, durable and flexible, and clearly demonstrate the orientation and branching pattern of the bronchial tree. The nature of the procedure also extends the availability of casts to laboratories or individuals with limited instrumentation and/or funding. Preliminary results using this technique to inject the lungs and certain air sacs of birds are also discussed. PMID- 2316326 TI - Ultrastructural aspects of the production of extracellular matrix components by the chick embryonic notochord in vitro. AB - The morphology of extracellular matrix (ECM) components and of the cell organelles, particularly the Golgi complex and its derived structures, implicated in the production of ECM in the chick embryonic notochord have been studied by transmission electron microscopy. Isolated notochordal fragments were cultured in suspension in liquid medium. Native striated collagen fibrils with a period of 540 A were observed in the perinotochordal sheath. Fine granular and filamentous materials suggestive of proteoglycans have been observed in intercellular spaces and under the basal lamina of the notochordal sheath. Golgi mature vesicles with structures resembling the previously described segment-long-spacing (SLS)-like aggregates and secretory vesicles probably containing proteoglycans or condensed collagen precursors have also been observed. PMID- 2316327 TI - Transverse diameter of the lumbar spinal canal in normal adult Saudis. AB - Pathological changes in the diameters of the lumbar spinal canal may be associated with low back pain. The assessment of the size of the canal is therefore an important diagnostic procedure. Evidence suggests that there are ethnic differences in the dimensions of the canal. A radiogrammetric study was therefore undertaken to establish norms of the transverse diameter for the Saudi population. The results show that the transverse diameter of the canal in Saudis differ from that of other populations, but the shape is similar to those of earlier reports. Intersegmental differences which are useful for the detection of isolated segmental anomalies were also calculated. The significance of the findings is discussed. PMID- 2316328 TI - Arterial supply of the human long biceps tendon. AB - The present study deals with the question whether an insufficient vascular supply of certain areas can be made responsible for ruptures in the biceps tendon. The macroscopic and microscopic examination shows that the blood supply of the tendon in the part most prone to ruptures, that is in the bicipital groove, is guaranteed even in older individuals. It is at least much better than in the intra-articular portion where ruptures are seldom observed. This means that mechanical components such as friction are dominant. The vascular factors seem to play a minor part. PMID- 2316329 TI - The influence of colonizing micro-organisms on development of crypt architecture in the neonatal mouse colon. AB - The effects of the normal colonizing microflora on postnatal development in the infant mouse were determined by comparison of crypt parameters in histological sections of the ascending colons of conventional specified-pathogen-free mice and their germ-free counterparts. Association of bacteria with the developing colonic mucosa in the third postnatal week caused a lengthening of the crypt column and depressed the total number of secreting goblet cells in each crypt. Thus the increasing bacterial burden during colonization of the developing colon was associated not only with expansion of the proliferative component of the crypt but also with modulation of the relative proportions of crypt cell populations. PMID- 2316330 TI - Arcade-like anastomoses between the posterior intercostal arteries in man. AB - The intercostal arteries of 12 nonpreserved human bodies were investigated: in 8 specimens they were injected with Latex for anatomical preparation, 4 specimens were radiographed after injection of Angiographin. Arcade-shaped anastomoses were consistently found to be present between neighboring intercostal arteries IV VIII; frequently, inconstant arcade-like communications were seen as far down as the 11th intercostal artery. The superior and inferior ends of each arcade were equidistant from the aorta as were the right and left arcades. Communications on the right side were stronger than those on the left. PMID- 2316331 TI - Effects of hypercalcemia-producing tumor extract and parathyroid hormone on osteoclast ultrastructure. AB - Hypercalcemia is a frequent complication of cancer. Recently, parathyroid hormone related protein has been isolated from tumors associated with this syndrome. In the present study, the effects of tumor-derived hypercalcemic factor and bovine parathyroid hormone (PTH) on bone were compared in an organ culture system using calvarial bones from newborn mice. Mouse calvaria were incubated for 72 h with control medium or media containing 0.15 mg/m tumor extract (TE) or 2 x 10(-9) M PTH. Bone resorption, as assessed by the amount of calcium released into the medium and the number of osteoclasts counted on light microscopy, was increased by both PTH and TE. On electron microscopy, areas for cytoplasm, ruffled border and clear zone were statistically increased in PTH- and TE-treated calvaria as compared to control. These values were not significantly different between PTH- and TE-treated calvaria. The study therefore demonstrates that the ultrastructural changes in osteoclasts induced by the hypercalcemia-producing TE are similar to those induced by PTH. PMID- 2316332 TI - [The arterial supply of the cervical vertebral body in newborns]. AB - The cervical vertebral column is mainly supplied by both vertebral arteries. A regular ladder pattern of arteries is on the dorsal plane as well as on the ventral plane of the cervical vertebral bodies, opposite to the thoracal and the lumbar area of the vertebral column with only a dorsal ladder pattern of arteries. The cervical arterial anastomoses are built by the segmental arteries of the vertebral arteries, in the back of the cervical vertebral bodies by the arteriae canalis vertebralis anteriores and in the front by the rami anteriores (corporum vertebrarum). The thyrocervical and the costocervical trunks are an additional blood supply especially to the ventral anastomoses. A loss of a segmental artery may have no effect because of the good anastomoses. Some decades of aa. nutriciae come in the vertebral body from all sides, but only 2 up to 4 rr. centrales anteriores and 2 rr. centrales posteriores join in the middle of the vertebral body. There are parallels to the arterial blood supply of the thoracal and the lumbar vertebral bodies. The longitudinal ligaments are supplied by both ladder patterns of arteries. PMID- 2316333 TI - [The arterial supply of the thoracic and lumbar spine in newborns]. AB - The major arteries supplying the vertebral column are definite. The branching arteries of these trunks are variable. The posterior intercostal arteries and the lumbar arteries have an ascending, descending or horizontal course. In accordance with the literature, we found large, arched anastomoses between the rami ascendentes and the rami descendentes arising from the rami canalis vertebralis anteriores on the dorsal plane of the vertebral bodies. There are also nearly horizontal junctions between the rr. ascendentes of both sides. We found junctions on the front of the thoracolumbar vertebral column at the end of the arteries. On the dorsal plane of the vertebral body 2 arteriae centrales posteriores originate from the rr. ascendentes. They run to the centre of the vertebral body. On the ventrolateral plane of the vertebral body 2 or 3 aa. centrales anteriores can be found. These 4 or 5 arteries join in the middle of the vertebral body. The blood supply of the thoracal and lumbar vertebral bodies does not differ essentially. Vessels come especially from lateral in the intervertebral disc. We suggest to name such a vessel ramus disci intervertebralis. The posterior longitudinal ligament is mainly supplied by the junction between the rr. ascendentes of both sides and the anterior longitudinal ligament by the aa. nutriciae in the thoracal and the lumbar area. PMID- 2316334 TI - Microangioarchitecture of gastric mucosa in man: antrum ventriculi. AB - The blood vessels of the antrum area of human gastric tunica mucosa have been studied by scanning electron microscopy and compared with vertical and horizontal serial sections of perfusion-fixed antrum mucosa. In contrast to previous studies on the oxyntic corpus mucosa, where two superimposed capillary layers could be seen, the antrum mucosa presents only one capillary layer. It extends from the lymphatic follicles above the lamina muscularis mucosae up to the luminal surface. No further arterioles exist in the glandular part of the antrum mucosa. The luminal aspect of the capillaries show thin, honeycomb-like capillaries, differing from our previous findings in the corpus area. There the capillaries are wide and circulate in a dense, convoluted way. Arteriovenous anastomoses again could not be seen in the examined tissue. The differences in gastric microangioarchitecture might be explained by the extent of the glandular part in both regions. The findings in the antrum area very much resemble the basal capillary layer in the corpus mucosa. The critical height for one capillary layer in the glandular tissue of human gastric mucosa is estimated to be approximately 1 mm. Larger diameters, as in the oxyntic corpus mucosa, might require a second capillary layer. PMID- 2316335 TI - Experimental reflux esophagitis in rats. A scanning electron-microscopic investigation. AB - We investigated the morphological alterations of the esophageal mucosa due to reflux disease by scanning electron microscopy. The esophagi of several rats were perfused with hydrochloric acid in the lower third, which was sealed towards the cardia with an inflatable catheter. Our findings indicate extensive erosion of the esophageal mucosa with detachment of the epithelial layer and underlying lamina propria from the lamina muscularis mucosae. The esophagi of control animals were perfused with physiologic saline solution and displayed no evidence of erosion or ulcerous alterations. PMID- 2316336 TI - Transplantation of the chick early eye primordium into a lensectomized optic cup of a host embryo. AB - Eye primordia of young chick embryos (stage XII) were transplanted into lensectomized optic cups of older embryos (stage XVII) to analyze the influence of the host retina on the degree of morphological differentiation attained by the donor lens. Embryos were sacrificed 24-96 h later. The donor lens primordium showed a differentiation more in correlation with the host eye cup (stage XXIII) after 24-96 h of incubation. PMID- 2316337 TI - First description of mechanoreceptors in the corpus adiposum infrapatellare of man. AB - The sensory innervation of the corpus adiposum infrapatellare of the human knee joint was studied by light microscopy. Small lamellated corpuscles (pacinian corpuscles) were found in the adipose tissue of the corpus adiposum infrapatellare. The lamellated corpuscles measured about 20 microns and consisted of 3-4 lamellae. It is discussed whether the corpus adiposum infrapatellare might perform a sensory function, influencing the muscle tone via polysynaptic reflexes. PMID- 2316338 TI - Growth and differentiation of fetal rat limb buds transplanted in athymic (nude) mice. AB - Limb buds of day 14 rat fetuses were cut into pieces and transplanted into the subcutaneous tissue of athymic (nude) mice. In day 14 fetal limbs, mesenchymal cells have begun to condense to form cartilaginous anlage, but no cartilage has been formed. Within 7 days after grafting, masses of hyaline cartilage developed. Numerous osteoblasts appeared, and new bone formation began by 14 days. By 20 days, osteoclasts appeared, and the formation of bone trabeculae and marrow cavities progressed. The cytological characteristics of chondrocytes, osteoblasts and osteoclasts were essentially the same as those seen in vivo. Many grafts developed into long bones, having the diaphysis and epiphysis. The mode of chondrogenesis and osteogenesis in the grafts was histologically similar to the corresponding process in vivo, although the differentiation was slower in the grafted limbs. Since the grafted limb buds showed remarkable growth and tissue differentiation for at least several weeks, this heterotransplantation system would be of potential use for the study of bone formation and resorption as well as for developmental toxicological studies. PMID- 2316339 TI - Plasticity of compensatory eye movements in rotatory tests. II. The effect of voluntary, visual, imaginary, auditory and proprioceptive mechanisms. AB - Two groups of 10 healthy volunteers each with a mean age of 28 years (17-39) were tested in low-frequency rotatory experiments (sinusoidal harmonic acceleration, SHA), at frequencies of 0.01-0.32 Hz. The purpose was to ascertain whether voluntary enhancement and reduction of gain and phase occurred with voluntary performances. The different tests were alertness in darkness, stationary and moving targets, imaginary stationary and moving targets in darkness, proprioceptive moving targets and acoustic stationary and moving targets. Alertness tests in darkness demonstrated a gain increase (0.5-0.7) at 0.01-0.32 Hz, and a decreasing phase lead (40-2 degrees) with increasing frequency. The alertness tests served as a reference for the other tests. In tests with stationary targets, the gain reached unity and the phase was almost 0 degrees. In imaginary stationary target tests, gain and phase were significantly increased compared with alertness. Stationary acoustic targets in darkness significantly enhanced the gain. An increased phase lead was also found. In visual suppression tests (moving target), the gain was near 0. In imaginary moving target tests, the gain decreased significantly. In darkness the gain was significantly more depressed with a proprioceptive moving target than during imaginary moving target. Testing with proprioceptive + acoustic moving target in darkness, displayed an additional gain depression and negative phase at 0.08 Hz. The conclusion is that the influence of non-vestibular mechanisms substantially affects low frequency sinusoidal rotatory testing. PMID- 2316340 TI - Cross-coupling between horizontal and vertical eye movements during optokinetic nystagmus and optokinetic afternystagmus elicited in microgravity. AB - The occurrence of horizontal jerks with larger amplitudes than on Earth was observed during vertical optokinetic nystagmus in astronauts tested throughout a 7-day spaceflight. During early exposure to microgravity, a horizontal spontaneous-like nystagmus was recorded in darkness following both vertical and horizontal optokinetic stimulation. In addition, the time constant of vertical OKAN with slow phase up was larger than on the ground. These effects disappeared on flight day 2. Then, the horizontal and vertical OKAN time constants decreased, and gradually returned to the preflight values, as previously observed with the gain of the vestibulo-ocular reflex. The early changes in microgravity are in agreement with those obtained on Earth in monkeys and humans during static tilt relative to gravity. Our findings suggest that the absence of otolithic input in microgravity may have an effect on the optokinetic system which could be mediated by the velocity storage mechanism. PMID- 2316341 TI - Effect of vestibulo-cerebellar lesions on asymmetry of vertical optokinetic functions in the squirrel monkey. AB - The role of the cerebellar uvula and nodulus in vertical optokinetic after nystagmus (OKAN) was studied in 4 squirrel monkeys. Aspiration ablation of the uvula and nodulus resulted in no significant change in the initial or peak gain of vertical optokinetic nystagmus (OKN) during the 24-week post-operative observation. However, the asymmetry of vertical OKAN was significantly altered. Using a protracted upward OK stimulus, slow phase-down OKAN-II, which was not seen pre-operatively, was significantly increased. In contrast, a downward OK stimulus produced little change in slow phase-up OKAN-II. Thus, the asymmetric degree of vertical OKAN-II was decreased after uvulonodulectomy. In addition, there was a post-operative reduction in the vertical oculomotor stability. When slow-phase eye velocity of OKAN was plotted along the time scale, the amplitude and frequency of the sinusoidal pattern was increased. OKAN-III and OKAN-IV were found in 50% of the monkeys after uvulonodulectomy. It is therefore thought that inhibition and directional control from the uvula and nodulus influence the stability and asymmetrical behaviour of the leaky integrator in the second order output system. PMID- 2316342 TI - Coherence analysis of scalp responses to amplitude-modulated tones. AB - Magnitude squared coherence is a method of auditory evoked potential (AEP) frequency-domain analysis, measuring the degree to which the AEP is determined by the stimulus as a function of frequency. In 10 normal-hearing human subjects, scalp responses to an amplitude-modulated (AM) tone (500 Hz carrier modulated with a 40 Hz envelope) were recorded. Critical value criteria were utilized in the statistical analysis of coherence-intensity functions for determination of threshold responses. When compared with subjective determination of AEP threshold from time-domain waveforms, coherence analysis provided a significantly (p less than 0.001) more sensitive threshold measure. Coherence analysis provides information on the spectral content of the response, and allows for the objective determination of threshold which may potentially be utilized in a more expeditious threshold measurement scheme. PMID- 2316343 TI - Aberrant frequency tuning and early stereociliary derangement in genetic inner ear disease. AB - We have developed an auditory brainstem response (ABR) based method for frequency selective forward masking tuning curve technique. Normative data from CBA/CBA mice are compared with tuning curves (TCs) from heterozygote dancer mice which in most cases initially had a normal ABR threshold. The sharpest tuning in normal mice was obtained at 10 kHz (Q10 = 7.6) and 12 kHz (Q10 = 10.9). With increasing age the mutants showed a broadening of the TC tip before ABR threshold impairment occurred. Morphological analysis of the cochleae from dancer mutants revealed an early disarray of hair cell stereocilia which became increasingly more severely affected with advancing age. We conclude that the broadening of the TC tip is an early finding in the genetically induced cochlear susceptibility which can be correlated to stereociliary dysfunction. PMID- 2316344 TI - Structurally based new functional interpretations of the subsurface cisternal network in human outer hair cells. AB - The system of subsurface cisterns (SSC) in human outer hair cells (OHC) was studied by high-resolution transmission electron microscopy (TEM). The SSC consist of only a single layer of cisterns, either flattened or tubular. The subsynaptic cisterns of efferent synapses are an integral part of the SSC. The outer leaflet of the SSC facing the cell membrane is connected to the OHC wall by pillars arranged in a highly regular and geometric pattern. The inner leaflet facing the cytoplasm displays an identical pattern of particles arranged in a star-like configuration so that pores are formed centrally. Pores are also identified at the outer leaflet and at the insertion of the pillars into the cell membrane. It is hypothesized that this highly specific organization of SSC, so far described only in the human OHC wall, is controlled by the efferent acetylcholine-mediated innervation. PMID- 2316345 TI - Melanocytes in the modiolus of the guinea pig cochlea. AB - The cochleae of pigmented and albinotic guinea pigs aged 6-8 weeks were examined by electron microscopy for melanocytes in the modiolus. Two different types of melanocyte were observed: i) The first (Type A) was characterized by spherical, uniformly pigmented stage IV melanosomes. No signs of melanogenesis were seen in this perivascular pigment cell form, which is found mainly in the region of the cochlear plexus. ii) The second, very rarely observed type of melanocyte (Type B) was characterized by fusiform to oval melanosomes in various stages of maturation. Connective tissue cells containing fusiform to oval melanosomes enclosed in membrane-bound vacuoles were frequently found. These two types can be regarded as corresponding to uveal (Type A) and dermal (Type B) melanocytes. The connective tissue of the cochlear plexus seems to be derived from the leptomeninx. PMID- 2316346 TI - Computer-aided three-dimensional reconstruction of the inner hair cells and their nerve endings in the guinea pig cochlea. AB - The inner hair cells and their nerve endings in the basal and third turns of the guinea pig cochlea were reconstructed three-dimensionally from serial thin sections by means of computer graphics. The inner hair cells showed narrowing below the cuticular plate and gradual increase in size toward the base where the surface was indented by nerve attachments. The sizes of the afferent nerve endings were in the range of 0.9 to 3.2 microns in cross section. Large endings were fewer and were located mainly on the pillar cell side, whereas small endings were numerous and were located on the modiolar side. The number of afferent nerve endings on a single cell in the basal turn averaged 26 and in the third turn, 17. All the afferent fibers were unbranched, most of them innervated a single cell, and 81% of them formed synapses with distinct synaptic bodies in the inner hair cells. A few afferent endings formed membrane specializations with two adjacent inner hair cells but the synaptic body was seen in only one cell. The number of efferent endings, from 0.08 to 2.0 micron in diameter, was about nine in the basal turn and was seven in the third turn. No significant difference was seen between the basal and third turns in cell shape, proportion of afferent to efferent endings, nor in morphology of synapses. PMID- 2316347 TI - Murine endolymphatic sac development in tissue culture: an in vitro model for sac function. AB - Numerous studies have attempted to elucidate the function of the mammalian endolymphatic sac (ELS). All of these studies have been performed on in vivo specimens and are thus influenced by humoral and tissue factors extraneous to the sac. In contrast, an in vitro model would provide an opportunity to study ELS cells in a carefully controlled environment. This report presents our experience with tissue culturing the murine endolymphatic sac removed from 16 and 18 gestational day fetuses. Light (LM) and transmission electron microscopical (TEM) evaluations of the developing endolymphatic sac were performed over periods of one, four, and seven days in tissue culture. In order to confirm growth and maturation, three-dimensional reconstructions from serial sections of the cultured ELS were made and compared with published accounts of in vivo murine ELS development for equivalent periods of time. Both whole and dissected otocysts were grown in tissue culture and compared with one another. Two different tissue culture medias were investigated, each with and without the addition of collagenase, used to soften the dense fibrous capsule of the otocyst and thus facilitate dissection and histological preparation. The impact of collagenase and the tissue culture medias on endolymphatic sac growth were studied. Results demonstrated that murine ELS cells were able to differentiate and mature in tissue culture, as confirmed by LM, TEM, and three-dimensional reconstructions. After an initial delay, in vitro maturation of cells in tissue culture paralleled normal in vivo growth and in some specimens appeared to show accelerated maturation. This in vitro model should prove useful in efforts to define ELS function and in providing a technique for tissue culturing human ELS from normal and diseased ears. PMID- 2316349 TI - Lymphocyte circulation to the middle ear. AB - The movement of lymphocytes into the tympanic cavity was studied during an immune response in the middle ear. Sensitized lymphocytes obtained from peripheral blood, peripheral lymph nodes, spleen, mesenteric lymph nodes and Peyer's patches of strain-13 inbred guinea pigs were labelled with 51Cr and injected intravenously into strain-13 recipients undergoing a middle ear immune response. The middle ears and immune organs of the recipients were assayed for radioactivity to detect the infiltration of labelled cells. Lymphocytes from all sources entered the middle ear mucosa in response to immune stimulation at equal levels, suggesting that the middle ear is seeded non-specifically by circulating lymphocytes in response to antigenic stimulation. The infiltration of lymphocytes of mucosal origin into the middle ear cavity is consistent with the participation of the middle ear in a defense system in common with other mucosal organs. PMID- 2316348 TI - Observations of cochlear microcirculation using intravital microscopy. AB - The guinea pig cochlea was prepared for visual observation of blood vessels using fluorescence intravital microscopic techniques. Measurements were made of the lateral wall vessels in the third cochlear turn and of the basilar membrane and lateral wall vessels in the first turn. A stable and consistent pattern of flow was observed under a variety of manipulations, including blood pressures of less than 20 mmHg. The rationale for the choice of observation areas in the cochlea and the specific vessel types studied at these locations are discussed. The change in blood velocity in cochlear blood vessels during pentoxifylline perfusion and during exsanguination are described. PMID- 2316351 TI - Re: Professor Ryo Takahashi's supplement: "Conceptualization in Endonasal Endoscopic Reconstructive Surgery of the Naso-paranasal Cavities: Imagination, Realisation and Reformation". PMID- 2316350 TI - Surfactant-like lamellar bodies in the mucosa of the human nose. AB - Specimens from the epithelium on the lateral wall of the human nose were examined under the electron microscope using a lipid and carbohydrate retaining method. In many of the ciliated epithelial cells and in some of the cells in the mucosal glands we identified multilamellated granules. These structures resembled lamellar bodies as found in normal alveoles where they are known to represent surfactant. The effect of phospholipid and the upper respiratory system is unknown but the similarities of these granules suggest to us a surface active function as it seems to play a role for normal Eustachian tube function. PMID- 2316352 TI - Campylobacter pylori and reflux oesophagitis. PMID- 2316353 TI - Acute intoxication with theophylline, proxyphylline and diprophylline in a 3 month-old infant after rectal application: pharmacokinetic data under hemoperfusion. PMID- 2316354 TI - Acute otitis media and facial palsy in children. AB - Two cases of facial palsy in connection with acute otitis media are presented. The patients were 2 months and 2 years old, respectively. In both cases the facial palsy disappeared after treatment with myringotomy and antibiotics. The etiological mechanisms behind and the different approaches to the treatment of facial palsy in children with acute otitis media are discussed. PMID- 2316355 TI - Abdominal mass: "fetus in fetu". AB - A female newborn presented a mass in the left upper abdominal quadrant. It was removed by surgery and contained two independent fetuses. Dissection and radiological study of the fetuses showed an axial skeleton and long bones. It corresponds to the generally recognized diagnostic criteria of fetus in fetu. PMID- 2316356 TI - Normal pattern of the cerebral function monitor trace in term and preterm neonates. AB - Cerebral Function Monitor (CFM) recordings were performed on 10 term and 19 preterm healthy infants. Term infants were monitored once, while preterm infants were followed serially. Forty-six recordings were made on 7, 14, 16 and 9 occasions in the age groups 30-31, 32-33, 34-35 and 36-37 weeks. All infants were examined clinically at 18 months of age and found healthy. By drawing weighted lines derived from the lower and upper limits of the CFM traces, mean values of minimum and maximum cerebral activity were calculated for the different age groups. In the term infants different CFM traces were identified corresponding to quiet sleep and active sleep. In the preterm infants a similar cyclic variability of the CFM trace was noted. A gradual increase in the minimum cerebral activity was found with increasing gestational age, resulting in a gradual narrowing of the trace. PMID- 2316357 TI - High total and free 1,25-dihydroxyvitamin D concentrations in serum of premature infants. AB - We investigated the relationship between serum total and free 1,25 dihydroxyvitamin D (1,25-OH2D) and the biochemical regulation of 1,25-OH2D production in premature infants. We measured 1,25-OH2D, vitamin D binding protein and related biochemical parameters and calculated the free 1,25-OH2D index in serum of 17 premature infants (birthweight 810-1700 g; gestational age 31-36 weeks) on two different occasions defined by body weight (Study A: 1,750-1,850 g, Study B: 2,100-2,200 g). Dietary calcium (Ca) intake was 1,5 or 2,6 mmol/kg/d, phosphorus (P) intake 1,7 mmol/kg/d and vitamin D intake 1,000 IU/d. Biochemical results were similar in infants with different Ca intakes and all were within reference ranges. Concentrations of vitamin D binding protein (Study A 0.15 +/- 0.03 g/l, Study B 0.14 +/- 0.03 g/l; means +/- SD) were lower, concentrations of 1,25 (OH)2D (Study A 180 +/- 67 pmol/l, Study B 216 +/- 53 pmol/l) were higher, and consequently the free 1,25-OH2D index (Study A 6.6 +/- 2.7, Study B 8.8 +/- 2.6) was 4 to 6 times higher than in previously studied term infants. 1,25-OH2D and the free 1,25-OH2D index increased significantly with age and were not correlated with serum P or parathyroid hormone. The data indicate that in premature infants with normal biochemical parameters of Ca and P metabolism elevated concentrations of 1,25-OH2D signify an increased fraction of free 1,25 OH2D and that increased production of 1,25-OH2D is not due to hypophosphatemia or hyperparathyroidism. PMID- 2316358 TI - Duplex versus unguided pulsed Doppler measurements of right ventricular output in newborn infants. AB - Noninvasive measurement of pulmonary artery blood flow has widespread implications for management of newborn infants requiring intensive care. Using a precordial, unguided, single Doppler technique, we evaluated right ventricular output in 26 preterm and 16 term infants without cardiopulmonary problems and compared it with right ventricular output obtained by duplex Doppler scanning and left ventricular output measured by a suprasternal single Doppler approach. Weights ranged from 1,120 to 3,960 g and postconceptional ages from 29 to 42 weeks. Unguided measurements of left and right ventricular output and guided and unguided measurements of right ventricular output were highly correlated (r = +0.92 and +0.95 respectively, p less than 0.001). The precordial single Doppler technique offers a reliable noninvasive estimate of right ventricular output in preterm and term newborn infants. PMID- 2316359 TI - Birthweight specific perinatal mortality in Greece. AB - Data from the Greek Perinatal Study in April 1983 revealed an excessively high perinatal mortality rate of 21.6 per 1,000 total births among singletons despite a low birthweight rate of only 4.5%. Comparison of perinatal mortality rates with Danish mortality rates in 1983, revealed the Greek rates to be three times higher than those in Denmark. When divided by time of death, the Greek stillbirth rates were two times higher and the early neonatal mortality rates were four times higher than the corresponding Danish rates. Subdivision of the Greek perinatal deaths using the Wigglesworth classification showed that the biggest group (40%) consisted of deaths associated with intrapartum asphyxia. The incidence of such deaths was 10 times higher than that found in Denmark. We conclude that in reducing the excessively high perinatal mortality rate in Greece special attention should be made to improve intrapartum and resuscitation techniques. PMID- 2316360 TI - Somatic growth in infants receiving prolonged caffeine therapy. AB - We have evaluated the longitudinal growth of 28 premature infants who had been treated by prolonged caffeine therapy (mean: 23.8 weeks). Routine follow-up included at least 5 physical examinations with measurement of length, weight and head circumference at the beginning of caffeine therapy, at mid therapy, at the end of the therapy and at 3 and 6 months after therapy. The distribution of the infants on the growth curves according to weight, length and head circumference showed a regular increase in growth parameters. Analysis of variance was highly significant at p less than 0.0001. We conclude that long term caffeine treatment does not adversely influence growth parameters, at least during early infancy. PMID- 2316361 TI - Predictive value of short-term growth using knemometry in a large population of healthy children. AB - We have analyzed the lower leg growth using a knemometer and the height growth using a stadiometer of 90 healthy children aged 3-16 years, for one year. The intra- and inter-individual monthly lower leg growth varied up to 4-fold, which was not accounted for by age or sex. The correlation between short term and annual lower leg growth rates increased with longer observation periods. There was no month-to-month consistency in the ratio of lower leg growth and height growth. There was no correlation between 1 month lower leg growth and annual height growth. The correlation increased with time. The 6-month observation interval was the interval with the highest predictive value for annual lower leg growth (R2 = 0.727) and annual height growth (R2 = 0.732). We conclude that growth of different parts of the skeleton and variable interval growth rates limits the ability of knemometry to predict long term growth. PMID- 2316362 TI - The importance of vitamin E in human nutrition. PMID- 2316363 TI - Plasma amino acids in term neonates and infants with phenylketonuria before and after institution of the diet. AB - The plasma amino acid concentrations were measured in 12 neonates with phenylketonuria (PKU). Blood samples were taken when fasting and two hours after a meal. The individual amino acid concentrations, the glycine/valine ratios, and the total amino acid concentrations were mutually compared and also compared to reference intervals. When the diet was instituted and plasma phenylalanine decreased, we observed a normalization of the postprandial response of isoleucine, leucine, tyrosine, and valine. PMID- 2316364 TI - Plasma amino acids in phenylketonuric children treated either with phenylalanine free amino acids or a protein hydrolysate. AB - The plasma amino acid concentrations were measured in 10 children with phenylketonuria (PKU) on the phenylalanine-free amino acid mixture Phenyldon and 9 PKU children on the phenylalanine-free protein hydrolysate Albumaid. The blood samples were taken fasting and two hours after the meal. The individual amino acid concentrations, the glycine/valine ratios, and the total amino acid concentrations were mutually compared and also compared to reference intervals. No differences of the concentration of phenylalanine on the two diet formulas were observed. Children on Phenyldon showed fasting and postprandial isoleucine higher than the reference intervals. Furthermore, a postprandial increase of several amino acids was observed on both diet formulas. This response was statistically significant in children on Phenyldon. PMID- 2316365 TI - Fibronectin in meningococcal sepsis. Correlation with antithrombin III and protein C. AB - Plasma fibronectin was measured with Laurell's immunoelectroassay in 44 patients with meningococcal sepsis. The average value (15.0 +/- 7.9 mg/dl) was lower than that in normal children (27.4 +/- 8.7 mg/dl) (p less than 0.001). Fibronectin in patients correlated positively with antithrombin III (AT-III) values (p less than 0.02), but not with protein C (0.05 less than p less than 0.1). The decrease of fibronectin had no prognostic value. The fibronectin levels were lower in patients with disseminated intravascular coagulation (DIC+), than in those without DIC (DIC-) (p less than 0.02), but were lower in both groups than in a normal control group. A negative correlation between fibronectin and protein C was only present in DIC- patients (r: -0.773 = p less than 0.01). Fibronectin varied independent of AT-III and protein C in DIC+ patients. The study was repeated in 11 patients 24 hours after admission when fibronectin had decreased in 7/11 cases (mean decrease: -2.7 +/- 8.7 mg/dl). This variation correlated in a negative way with AT-III (r: -0.659 = p less than 0.05). In meningococcal sepsis fibronectin decreases very early, even in DIC- patients and its relationship to AT-III and protein C is different, depending on the presence of DIC and on the stage of evolution of the disease. PMID- 2316366 TI - Exercise therapy and hypocaloric diet in the treatment of obese children and adolescents. AB - Fourteen obese children and adolescents were treated with a combined therapy of low calorie diet and exercise and their progress compared to that of 11 obese children treated with diet only. Children treated with combination therapy were encouraged to perform aerobic exercises daily, for a period of time which was calculated to consume approximately 250 kcal per exercise session. After 4 months of therapy, a significantly (P less than 0.05) larger decrease of % overweight was observed in the group of children treated with diet and exercise (-25 +/- 13.5%) than in those treated with diet only (-15.8 +/- 10.5%). Treatment compliance was better in the group treated with diet and exercise than in the group which followed a low calorie diet only. We think that unsupervised exercise therapy can be successfully combined with a low calorie diet in the treatment of childhood obesity. PMID- 2316367 TI - Child sexual abuse. Characteristics of the assaults in a population of children, 0-17 years of age, molested by a relative or an acquaintance. AB - Thirty-eight children, 0-17 years of age, suspected to have been sexually abused by a relative or an acquaintance were psychiatrically evaluated. The suspicions had developed in various ways: through accounts given by the child, through the child's contacts with a person suspected of having abused another child, through a witness or through conclusions drawn, for instance, from changes in behaviour or play patterns of the child. Genital fondling was the most common sexual act reported. The children usually described repeated abuse. The duration of the abuse situation was more than one year in the majority of the cases. PMID- 2316368 TI - Child sexual abuse. The suspects, the suspicions and the background. AB - In a study of suspected cases of child sexual abuse, 22 persons (21 men and one woman) were identified as probable perpetrators according to the child psychiatric evaluation. Eight perpetrators admitted abuse, although denying certain aspects of the allegations, and two persons made what was categorized as partial confirmations. Nine cases led to a charge and eight of these to a conviction. Disease, addiction, sexual frustration, unwanted separation, ageing and adolescence were identified as factors which in individual cases seemed to have influenced a person's predisposition to abuse children sexually. PMID- 2316369 TI - Immunohistochemical analysis of estrogen receptors in human gallbladder. AB - Estrogen receptors (ER) in human gallbladders were examined immunohistochemically using a specific monoclonal antibody against human ER. ER immunoreactivity was positive in 6 (19.4%) of 31 cases of cholelithiasis, 6 (33.3%) of 18 cases of epithelial polyp, 14 (53.8%) of 26 cases of adenoma, and 26 (22.8%) of 114 cases of adenocarcinoma. ER immunoreactivity was located at the nucleus of the epithelium of both non-neoplastic and neoplastic tissues, although the number of ER-immunoreactive cells was small. There was no sex difference in the incidence of ER immunoreactivity. No significant difference in survival rates could be demonstrated between ER-positive and ER-negative carcinomas. Epithelial polyps, adenomas and carcinomas were divided into metaplastic type and non-metaplastic type based on the presence or absence of metaplastic changes for comparison of the incidence of ER immunoreactivity. The incidence of ER immunoreactivity in the metaplastic type was significantly higher than that in the non-metaplastic type. We conclude that ER are present in the gallbladder mucosa in various disease states and suggest that the presence of ER is related to metaplasia of the gallbladder mucosa. PMID- 2316370 TI - Ultrastructural study of the human pineal gland in aged patients including a centenarian. AB - An ultrastructural study of human pineal glands obtained at autopsy from 7 patients older than 70 years was conducted in order to clarify the functional anatomy of the pineal in the aged. By light microscopy, the pineal glands from aged patients were parenchymatous and almost indistinguishable from those of younger controls. Electron microscopy of the pineal parenchymal cells revealed deep nuclear indentations, synaptic ribbons and ribbon fields, Golgi apparatus, lipofuscin granules and microtubular sheaves in all subjects, cilia with a 9 + 0 pattern in a few, and lamellated structures suggestive of the outer segment of photoreceptor cells very rarely. Microtubules were numerous in the cytoplasmic processes and bulbous endings. Fibrous astrocytes located between the pinealocytes showed long and thin cytoplasmic processes containing numerous glial filaments. Two types of nerve bouton were present in the pineal parenchyma, one of which contained clear vesicles forming synapse-like contacts with pinealocytes. There were no significant age-related changes in these features in a qualitative comparison with pineal glands from 5 adult patients younger than 70 years. These findings indicate that even in advanced age, the human pineal gland maintains some functions, such as intercellular communication and photoreception, in common with the pineal in lower vertebrates. PMID- 2316371 TI - Studies on pulmonary anthracosis. With special reference to the mineral constitution of intrapulmonary particulate pollutants in the human lung. AB - In order to investigate anthracosis of the human lung, especially its causal relationship with atmospheric pollution and the occurrence of lung cancer, intrapulmonary particulate pollutants (IPP) from autopsy cases and patients lobectomized because of lung cancer were separated by alkali digestion of the lung tissue, and their elemental constitution was analyzed by a wavelength dispersive X-ray fluorescence spectrometer. Silicon was the most abundant mineral constituent of non-carbonaceous fraction of IPP, followed by calcium, magnesium, iron, aluminum and other trace elements. The levels of silicon and aluminum in IPP were significantly higher in individuals treated at Saitama Medical School Hospital than in those from Tokyo. Farmers showed higher levels of silicon and aluminum than other occupational categories, whereas male blue-collar workers showed higher levels of calcium and lead than farmers. The level of iron in IPP of male smokers tended to be higher than in non-smokers. In cases of lung cancer, especially of the hilar type, the levels of iron, calcium, copper, lead, chromium and nickel in IPP tended to be higher than in non-lung cancer cases, whereas the levels of silicon and aluminum were lower than in non-lung cancer cases. On the basis of these results, pulmonary anthracosis was considered to be etiologically related to the occurrence of lung cancer. PMID- 2316372 TI - An autopsy case of peritoneal malignant mesothelioma in a radiation technologist. AB - A case of peritoneal malignant mesothelioma in a radiation technologist, who had worked in this field for 34 years, is reported. Histopathologically, a biopsy specimen from the retroperitoneal tumor revealed a biphasic type of malignant mesothelioma. Electron microscopy disclosed that the tumor cells contained prominent microvilli, basal laminae adjacent to the stroma, junctional complexes, desmosomes, tonofilaments, clusters of glycogen granules, well developed rough endoplasmic reticulum (RER), confronting cisternae showing direct continuity with the RER and membrane-bound granules suggestive of secretory activity. No increased amount of asbestos was detected in autopsied lung material or the peritoneal mesothelioma. The estimated cumulative dose of occupational irradiation was calculated to be about 40 to 50 rad at most. Irradiation was discussed in relation to the etiology of the peritoneal mesothelioma. PMID- 2316373 TI - Pulmonary alveolar proteinosis and disseminated atypical mycobacteriosis in a patient with busulfan lung. AB - A 32-year-old Japanese man with chronic granulocytic leukemia died of respiratory failure. Autopsy revealed alveolar proteinosis and pulmonary fibrosis, complicated by disseminated atypical mycobacteriosis. Epithelial hyperplasia caused by busulfan therapy was probably responsible for the induction of excessive surfactant production, resulting in alveolar proteinosis, and the immunosuppressive state due to chronic granulocytic leukemia was probably related to the induction of disseminated atypical mycobacteriosis. PMID- 2316374 TI - Massive ovarian edema associated with polycystic ovary. AB - A 14-year-old girl with massive ovarian edema (MOE) of the right ovary and a polycystic ovary is presented. The right ovary was moderately enlarged and incompletely twisted. Histologically, it showed diffuse interstitial edema and multiple cysts, frequently surrounded by a line of luteinized cells. Such cysts are suspected to consist of highly degenerative ovarian follicles, in addition to an edematous corpus albicans and cystic change in the edematous stroma. Focal edematous change and occasional indefinite cystic structures, as seen in the left polycystic ovary of our patient, indicate an early stage of MOE. The pathogenesis of MOE in the present case was therefore suspected to be based on the underlying state of bilateral polycystic ovary. The luteinized cells would have been derived from granulosa cells and from the internal theca cells of the follicles in addition to stromal cells. PMID- 2316375 TI - Sex-linked variation in creatine kinase release, and its dependence on oestradiol, can be demonstrated in an in-vitro rat skeletal muscle preparation. AB - Creatine kinase (CK) release from male and female rat soleus muscles was studied for 4.5 h in vitro, under basal conditions and after electrical stimulation. Basal CK release was greater from male than from female muscles, and CK release from male muscles increased significantly when the muscle tension in the in-vitro set-up was increased. CK release after electrical stimulation was also more marked in male soleus muscles. Pretreatment of male rats and ovariectomized female rats with oestradiol for 3 weeks attenuated the enzyme efflux, but ovariectomy 24 h before in females, or oestradiol administration 24 h before in males, did not affect the release of CK in vitro. The data show that sex-linked differences in CK efflux are still present, under both basal and stimulated conditions, when muscles are isolated from the intact animal, and that hormone treatment of the intact animal affects these properties in the isolated muscle in vitro. PMID- 2316376 TI - Differences in cardiorespiratory responses during and after arm crank and cycle exercise. AB - The differences in cardiorespiratory responses were examined during and after intermittent progressive maximal arm-crank and cycle exercise. Arm-crank exercise was performed in a standing position using no torso restraints to maximize the amount of active skeletal muscle mass. Recovery was followed for 16 min. In the tests a variety of ventilatory gas exchange variables, heart rate, the blood pressure, and the arm venous blood lactate concentration were measured in 21 untrained healthy men aged 24-45 years. At equal submaximal external workloads for arm cranking and cycling (50 and 100 W) the respiratory frequency, tidal volume, pulmonary ventilation, oxygen uptake, carbon dioxide output, the respiratory exchange ratio, heart rate, the arm venous blood lactate concentration, and the ventilatory equivalent for oxygen were higher (P less than 0.001) during arm cranking than cycling. The maximal workload for arm cranking was 44% lower than that for cycling (155 +/- 37 vs 277 +/- 39 W, P less than 0.001) associated with significantly (P less than 0.001) lower maximal tidal volume (-20%), oxygen uptake (-22%), carbon dioxide output (-28%), systolic blood pressure (-17%) and oxygen pulse (-22%) but a higher ventilatory equivalent for carbon dioxide (+22%) and arm venous blood lactate concentration (+37%). However, these responses after arm-crank and cycle exercises behaved almost similarly during recovery. The high cardiorespiratory stress induced by arm work should be taken into account when the work stress and work-rest regimens in actual manual tasks are assessed, and when arm work is used for clinical testing, and in physiotherapy particularly for patients with heart or pulmonary diseases. PMID- 2316377 TI - Cardiovascular responses to carotid sinus baroreceptor stimulation during moderate to severe exercise in man. AB - Our objective was to assess the importance of arterial baroreflexes in maintaining vasoconstriction in active muscle during moderate to severe exercise. Eight subjects exercised for 8-15 min on a cycle ergometer at three levels (averages 94, 194, 261 W) requiring 40-88% of VO2 max. Four times during each exercise level pulsatile negative pressure (-50 mmHg) was applied over the carotid sinuses for 30 s; suction was applied at each ECG R-wave for 250-400 ms. Before and during each neck suction, femoral venous blood flow (FVBF) was measured by constant infusion thermal dilution. At 94 W neck suction significantly reduced blood pressure (BP) (15 mmHg) and heart rate (HR) (7 beats min-1), and raised leg vascular conductance (LVC) (11.4%) without changing FVBF. At 194 W, neck suction reduced BP (9 mmHg), HR (4 beats min-1) and FVBF (5.1%, 240 ml min-1), and raised LVC (5.2%). At 261 W, LVC was unchanged by neck suction, but BP and FVBF both fell (9 mmHg and 650 ml min-1 or 7.4%). We conclude that competing local vasodilation and sympathetic vasoconstriction control muscle blood flow during moderate exercise, and vasoconstrictor tone can be withdrawn by baroreceptor stimulation. High levels of vasoconstrictor outflow to muscle in severe exercise may not originate from baroreflexes. PMID- 2316378 TI - Cardiovascular and endocrine responses to haemorrhage in the pig. AB - Heart rate (HR), mean arterial pressure (MAP), indices of sympathetic and parasympathetic activity (plasma concentrations of adrenaline, noradrenaline and pancreatic polypeptide, PP), vasopressin (VP) and aldosterone (ALDO) were measured in six pigs during continuous bleeding resulting in hypovolaemic shock, from which five survived. Three stages of haemorrhage could be defined. Stage I. Resting MAP was 85 +/- 6 mmHg and increased to 96 +/- 5 mmHg with a blood loss of 275 (range 250-300) (10 (9-12)% of the estimated blood volume) concomitant with an increase in HR from 105 +/- 5 to 113 +/- 6 beats min-1 (P less than 0.05). Stage II. After a blood loss of 375 (300-500) ml (15 (13-16)%) MAP fell to 62 +/- 9 mmHg and HR to 95 +/- 5 beats min-1 (P less than 0.05). Stage III. A blood loss of 1113 (825-1450) ml (44 (30-52)%) resulted in a MAP of 50 +/- 4 mmHg and an increase in HR to 206 +/- 3 beats min-1 (P less than 0.05). Adrenaline increased from 0.3 +/- 0.1 to 0.8 +/- 0.3 (stage II) and 3.6 +/- 1.1 nmol l-1 (stage III) (P less than 0.05); noradrenaline from 0.4 +/- 0.1 to 1.5 +/- 0.4 (stage II) and 5.9 +/- 1.7 nmol l-1 (stage III) (P less than 0.05); PP from 6.2 +/- 1.6 to 13.3 +/- 2.3 (stage II) and 20.9 +/- 7.8 pmol l-1 (stage III) (P less than 0.05). VP changed only marginally, but ALDO increased from 496 +/- 54 to 623 +/- 76 pmol l 1 (stage III) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316379 TI - Effects of acute administration of omeprazole or ranitidine on basal and vagally stimulated gastric acid secretion and alkalinization of the duodenum in anaesthetized cats. AB - Experiments were performed on acutely vagotomized cats during chloralose anaesthesia. In order to avoid sympathoadrenergic influences, the adrenal glands were ligated and the splanchnic nerves were cut bilaterally in all animals. The gastric lumen was perfused with saline and the H+ secretion was calculated from pH measurements in the perfusate. HCO3- secretion by the duodenal mucosa was titrated in situ. Omeprazole (4 mg kg-1 i.v., dissolved in PEG400, 40% w/v) did not influence basal or vagally induced HCO3- secretions, but inhibited by about 80% the H+ secretory response induced by electric vagal stimulation. Acute administration of ranitidine (5 mg kg-1 i.v.) transiently lowered arterial pressure, an effect which was followed by a sustained compensatory tachycardia. Ranitidine raised basal duodenal HCO3- secretion by 50% and inhibited vagally induced gastric H+ secretion by about 70%, whereas vagally induced HCO3- secretion was not influenced. The results suggest that vagal nerve stimulation raises the duodenal bicarbonate secretion via a mechanism independent of the level of gastric H+ secretion. PMID- 2316380 TI - Intestinal fluid transport in the small intestine of normotensive and spontaneously hypertensive rats: the importance of enteric nerves, chloride and bicarbonate secretion. AB - Fluid transport was studied in periarterially denervated jejunal segments of spontaneously hypertensive rats (SHR) of the Okamoto strain and as a control also in Wistar-Kyoto rats (WKR). In agreement with the findings of an earlier report a 'spontaneous' fluid secretion was observed in SHR whereas the intestinal segments of WKR absorbed fluid. The fluid secretion in SHR was inhibited by tetrodotoxin or lidocaine placed on the serosal surface of the intestinal segment under study. These observations confirm our earlier proposal that secretory nervous pathways in the enteric nervous system evoke the fluid secretion in SHR. In an attempt to analyse the cellular mechanisms that underlie the fluid secretion in SHR the animals were given loop diuretics in doses that evoked diuresis. No effect on intestinal fluid transport was seen in SHR or WKR. Furthermore, to study the importance of bicarbonate transport alkaline secretion was monitored with a pH stat technique. In the initial part of the experiments the alkaline secretion in SHR and WKR was similar. In half of the SHR experiments alkaline secretion increased with time. This increase could be completely reversed with hexamethonium and atropine (only tested in three experiments). The time course of the alkaline and fluid secretion in SHR did not coincide, indicating that bicarbonate ion transport was not the major cause of fluid secretion in SHR. In agreement with this conclusion it was observed that acetazolamide (a blocker of carbonic anhydrase) did not influence rate of fluid transport in SHR or WKR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316381 TI - Uptake of ascorbic acid by freshly isolated cells and secretory granules from the intermediate lobe of ox hypophyses. AB - Mechanically isolated cells from the intermediate lobe of ox hypophyses contained 40.6 +/- 3.7 nmol mg-1 protein (mean +/- SE, n = 5) of ascorbic acid. They accumulated radioactivity time dependently, on incubation with L-[14C]ascorbic acid in ionic medium dominated by NaCl. No definite saturation of uptake occurred when mechanically isolated cells were incubated with increasing ascorbic acid concentrations up to 0.6 mM. But if such cells were purified on a Percoll gradient, a clear saturation of uptake could be observed. Acetylsalicylic acid reduced the uptake markedly. When cells loaded with L-[14C]ascorbic acid were homogenized and placed on a Percoll gradient, the radioactivity was recovered in several subcellular fractions. Decrease of the Na+ concentration or presence of ouabain in the medium did not cause noticeable changes in uptake by non-purified cells, whereas uptake by purified cells was clearly sodium-dependent. Phloridzin inhibited uptake. Secretory granules from pars intermedia contained 40.0 +/- 3.8 nmol mg-1 protein of ascorbic acid (mean +/- SE, n = 3) and could accumulate L [14C]ascorbic acid rapidly in a KCl-dominated medium. The uptake was not saturable with ascorbic acid concentration and was not influenced by the presence of I mM ATP + I mM Mg2+ in the medium. The concentration of copper and iron in isolated cells was comparable to that in isolated neurohypophysial nerve terminals, whereas the concentration of zinc was considerably higher in the pars intermedia cells. The concentration of Cu, Zn, Fe and Co in secretory granules from pars intermedia was higher than in secretory granules from neurohypophyses. PMID- 2316382 TI - Changes in gastric EGF, EGF receptors and acidity during healing of gastric ulcer in the rat. PMID- 2316383 TI - Post-natal changes in growth of rat proximal tubule cells: a study of cells in short primary culture. PMID- 2316384 TI - Maternally administered epidermal growth factor stimulates fetal growth in the rat. PMID- 2316385 TI - Diffusion from the cerebrospinal fluid as a nutritional pathway for spinal nerve roots. PMID- 2316386 TI - Discrimination of cardinal compass directions. AB - The study tested the hypothesis that east-west is more difficult to discriminate than north-south because pre-experimentally the former is associated with right left and the latter with up-down (or front-behind). Forty-eight undergraduates first learned north, south, east, and west in slides of unknown places. In one condition the compass directions were indicated by labels. Arrows presented in the plane of the slides were in other conditions used to create different associations between the compass directions and the egocentric directions right left and front-behind. In a subsequent RT task subjects indicated if the directions were the same or different in two consecutively presented slides. No reliable effects were found for same responses but different responses supported the hypothesis in being slower for east-west than north-south when associated with right-left (or left-right) and faster when associated with front-behind (or behind-front). PMID- 2316387 TI - The influence of near-threshold priming on metamemory and recall. AB - A metamemory paradigm involving the use of near-threshold visual priming is developed in which a brief flash of a previously nonrecalled answer occurs, and then the person attempts to recall the answer and/or make feeling-of-knowing judgments. The major new finding is that the feeling of knowing did not detect perceptual input from a near-threshold prime that increased the recall of otherwise nonrecallable items. This finding has two important implications: (1) The feeling of knowing is not always more sensitive than recall as an indicant of information in memory (particularly, as an indicant of small amounts of information newly deposited into memory), and (2) 'monitored' information (that the feeling of knowing would be capable of detecting, as examined in previous research) can be combined with 'nonmonitored' information (that is newly deposited into memory and that the feeling of knowing does not detect) so as to produce the successful recall of an otherwise nonrecallable item. PMID- 2316388 TI - Large and rapid improvement in form discrimination accuracy following a location precue. AB - Processing of a visual stimulus can be improved by precuing its location. Most previous precue studies have used reaction time as the dependent measure and have found large effects; but when form discrimination accuracy has been used, precue effects have been relatively small. The present experiments yielded large, short latency precue effects on form discrimination accuracy. A small square precue was briefly presented near one of four possible target locations. Then one of four possible targets (T-like figures) was presented in each location, followed by a mask. Observers attempted to identify the target that had been presented in the cued location. In experiment 1, target duration, cue-to-target distance, and cue target onset asynchrony (SOA) were varied. Target discriminability (d') increased markedly with increasing precue-target SOA, even at very short SOAs. Thus, there was no evidence for a delay in the onset of precue effects (caused, for example, by the need to shift attention across the visual field). Performance was best for precues that were closest to the target, thus ruling out a forward masking explanation of the effect. Finally SOA and target duration interacted strongly - longer precue SOAs resulted in larger effects of target duration. In experiment 2, this interaction was replicated using an additional target duration and longer SOAs. One interpretation of this result is that focal attention increases the rate at which information can be extracted from a visual location. PMID- 2316389 TI - Fifth International Symposium on Bioluminescence and Chemiluminescence. Florence Bologna, Italy, September, 1988. Proceedings. PMID- 2316390 TI - A sensitive and rapid luminescence sandwich assay for antibodies to hepatitis-B surface antigen (anti-HBsAg). AB - A chemiluminescent assay for hepatitis-B surface antigen is described which used an isoluminol derivative as the label. The assay is precise intra-assay CV, 1.96 2.45%; inter-assay CV, 5.26-8.11% and has a lower detection limit for hepatitis-B surface antigen of 1.3 U/l. PMID- 2316391 TI - Optimization of an HPLC peroxyoxalate chemiluminescence detection system for some dansyl amino acids. AB - Bis(2,4,6-trichlorophenyl) oxalate (TCPO)-hydrogen-peroxide-generated chemiluminescence (CL) of four dansyl amino acids has been used as a model system for the optimization of a detection system in reversed-phase high-performance liquid chromatography. Dansylated alanine, glutamic acid, methionine, and norleucine were subjected to peroxyoxalate induced CL in a static system and in a flow system under various conditions with respect to TCPO (ethyl acetate) and hydrogen peroxide (acetone) concentrations, solvent composition and flow, using a two-pump or a one-pump post-column reagent system. From the CL-decay curve, the influence on the emission signal from the total flow rate in the detector was investigated. Special attention was focused on the mixing of the LC eluate and the reagent in order to combine an efficient collection of the emitted light using a 74 microliter flow cell (originally 10 microliters in the fluorescence detector) with minimal extra column band broadening. Therefore, a capillary fused silica tubing of about 100 microns i.d. was inserted against the end-frit of the column and brought through a mixing tee, in which the solutions of TCPO and hydrogen peroxide were added. The column end tubing ended in the flow cell and the LC eluate and the reagents were mixed when entering the flow-cell. Average detection limits (S/N = 2) of 200 fmol injected dansylated amino acid could be reached. A comparison is made between the use of TCPO and DNPO (bis (2, 4 dinitrophenyl) oxalate). PMID- 2316392 TI - The chromophore of pholasin: a highly luminescent protein. AB - Pholasin is the photoprotein extracted from the marine bivalve Pholas dactylus. It undergoes an oxidative chemiluminescent reaction to oxypholasin with superoxide anion, hypochlorite, peroxidases and other oxidants. Since the observed absorbance and chemiluminescent emission spectra of pholasin solutions cannot be brought about solely by the amino acids composing the protein, there has to be a chemiluminescent chromophore. However, little is known about the chemical nature of this molecule. This work seeks to identify the chemical structure of the luminescent prosthetic group of pholasin. Pholasin could not be reactivated using chromophores from the hydroid Obelia geniculata (coelenterazine) and from the ostracod shrimp Vargula (formerly Cypridina) hilgendorfi. Furthermore, the reaction product of the Vargula chromophore could not be detected in solutions containing oxypholasin. Fluorescence analysis of such a solution revealed a compound with an emission spectrum (lambda max 480 nm; excitation at 320 nm), resembling the emission spectrum of the chemiluminescent reaction. This fluorescent substance was separated by gel filtration. It exhibited an apparent molecular mass of less than 2000. Fluorescence measurements of extracts of partially purified pholasin suggested that a flavin moiety may be involved in pholasin luminescence. PMID- 2316393 TI - Enhanced chemiluminescent immunoassay for aldosterone. AB - A solid phase immunoassay for aldosterone using enhanced chemiluminescent detection has been developed. Monoclonal antibodies against aldosterone were used for the immune reaction and compared with polyclonal antibodies. Uniform Protein A coated polystyrene tubes were used as solid phase for the monoclonal antibody and second (anti-rabbit) antibody coated tubes for the polyclonal antibody. Horseradish peroxidase was covalently linked to aldosterone as enzyme label. Optimum conditions were established for the generation and measurement of the luminescent reactions using luminol, p-iodophenol as enhancer and hydrogen peroxide. The advantages of this assay are the high sensitivity with a detection limit of 100 fg/tube, the prolonged luminescence signal with a simplification of the measurement (simpler detectors, external start pipetting) and the short measure time with the possibility of repeated measurement. The coefficients of variation were 4.2%-7.3% in the concentration range 140-1180 pmol/l. The assay showed a significant correlation (r = 0.91) with the ELISA. The aldosterone concentrations in plasma and saliva of patients with Conn's syndrome were significantly increased, and in patients with Addison's disease were found near the detection limit. PMID- 2316394 TI - Isoluminol as a marker in direct chemiluminescence immunoassays for steroid hormones. AB - We have used isoluminol steroid hormone conjugates in competitive heterogeneous chemiluminescence immunoassays (CIA) for estradiol, progesterone and estriol in body fluids. The assays did not require prior extraction of the steroid hormone with an organic solvent. Polyclonal or monoclonal antibodies, covalently coupled to polyacrylamide microspheres or adsorbed onto the plastic surface of microtritation plates via an intermediate second antibody, were used as solid phase. The latter solid-phase system allows rapid processing of incubation mixtures. Sensitive and reliable direct CIAs for estradiol in serum, progesterone in serum and in saliva and for estriol in saliva have been developed and their clinical utility has been assessed. Sensitivities ranged from 0.54 to 0.04 nmol/l, and precision (% CV) ranged from 10% to 16%. PMID- 2316395 TI - Fibre-optic biosensor based on luminescence and immobilized enzymes: microdetermination of sorbitol, ethanol and oxaloacetate. AB - We have investigated highly selective and ultrasensitive biosensors based on luminescent enzyme systems linked to optical transducers. A fibre-optic sensor with immobilized enzymes was designed; the solid-phase bioreagent was maintained in close contact contact with the tip of a glass fibre bundle connected to the photomultiplier tube of a luminometer. A bacterial luminescence fibre-optic sensor was used for the microdetermination of NADH. Various NAD(P)-dependent enzymes, sorbitol dehydrogenase, alcohol dehydrogenase and malate dehydrogenase, were co-immobilized on preactivated polyamide membranes with the bacterial system and used for the microdetermination of sorbitol, ethanol and oxaloacetate at the nanomolar level with a good precision. PMID- 2316396 TI - Chemiluminescence of bronchoalveolar lavage cells as an indicator of leukocyte activation in rats with a hyperreactive bronchus. AB - Activation and generation of inflammatory mediators by different leukocytes may be important in the pathogenesis of airway hyperreactivity. We studied the effect of active sensitization with ovalbumin as antigen and i.v. treatment with Sephadex particles on bronchial reactivity (BR) in rats and its possible relation to leukocyte infiltration (LI) and activation (LA) in bronchoalveolar lavage (BAL). A marked BR to aerosols of serotonin (5-HT) and ovalbumin was found in Sephadex treated animals but not in control animals. In parallel to this a marked increase in BAL cell count from Sephadex-treated animals compared to controls was seen. This increase in BAL cell count corresponded with a clear augmentation of spontaneous, buffer-induced and C3Z-induced, luminol-amplified CL. We deduce that detection of CL of BAL cells from rats might be used for studying inflammatory mechanisms which lead to a hyperreactive bronchus. PMID- 2316397 TI - Effects on bone of primary hyperparathyroidism. PMID- 2316398 TI - Circulating concentrations of parathyroid hormone-like peptide in malignancy and in hyperparathyroidism. AB - We have examined circulating concentrations of a parathyroid hormone-like peptide (PLP) in patients with malignancies and in patients with hyperparathyroidism. The radioimmunoassay employed reacts with synthetic amino-terminal fragments of PLP but not with parathyroid hormone. Elevated plasma PLP concentrations were observed in 50% of patients with malignancy and hypercalcemia and in 15% of normocalcemic cancer patients, mean values being higher in the former group. Detectable plasma PLP concentrations were found in 2 of 39 control subjects. In 2 patients with breast cancer plasma PLP declined concomitantly with a reduction in tumor burden. Adenocarcinoma of the breast and squamous cell carcinomas were most frequently associated with high plasma PLP levels although a variety of histologic types were represented. The presence of metastases on bone scans did not correlate with either the severity of hypercalcemia or the extent of PLP elevation. Increased concentrations of plasma PLP were also observed in 4 of 20 patients with primary hyperparathyroidism and in 5 of 16 patients with chronic renal failure and secondary hyperparathyroidism. Gel filtration analysis of immunoreactive PLP in plasma from 2 hypercalcemic breast cancer patients revealed heterogeneity, with, in each case, both large (greater than 15 kD) and small (6-7 kD) molecular weight amino-terminal moieties. The results document the presence of PLP in the circulation of patients with cancer and are consistent with a pathogenetic role for PLP in the hypercalcemia of malignancy irrespective of whether skeletal metastases have occurred. PLP may also contribute to the skeletal and/or renal manifestations of hyperparathyroid states. PMID- 2316399 TI - Parathyroid hormone, but not prostaglandin E2, changes the shape of osteoblasts maintained on bone in vitro. AB - Parietal bones from 2-week-old rats were dissected free from the sutural regions, dura mater, and periosteum, leaving the surface covered with osteoblasts and some osteoclasts. Prostaglandin (PG) production by these "stripped" bones under basal conditions and after exposure to parathyroid hormone (PTH) was measured by radioimmunoassay of the culture medium (minimum essential medium with or without added 10% heat-inactivated fetal calf serum). Cultured specimens were examined by scanning electron microscopy for changes in osteoblast length, orientation, ruffling, and overlap. As demonstrated previously, PTH caused the osteoblasts to elongate, align, and show fewer ruffles compared to controls. PTH increased PG synthesis by the stripped bones. Indomethacin inhibited PG formation but did not affect the osteoblast shape change. PGE2, indomethacin, or both drugs together had no discernible effect on any morphologic features. These findings indicate that PGE2 does not change osteoblast shape and that the cell shape change with PTH is not mediated by endogenous prostanoids. PMID- 2316400 TI - A scanning electron microscopic and photon absorptiometric study of the development, prolongation, and pattern of recovery from lactation-induced osteopenia in rats. AB - Measurements by scanning electron microscopy (SEM) of femoral hemisections confirmed and amplified results by single-photon absorptiometry that had shown a marked increase in lactation osteopenia in rats fed a low-calcium diet (LCD, 0.04% Ca) as compared with a medium-(adequate) calcium diet (ACD, 0.4% Ca). SEM of bones from rats at the end of lactation on either diet showed a large loss of trabecular bone, increased porosity of endosteal surfaces, and cortical thinning. These changes were much more striking in LCD rats than in ACD rats. Backscattered electron imaging of cross sections of the femora revealed marked cortical thinning at midshaft after lactation, especially in rats on the LCD; this method also showed a marked increase in newly formed, less dense diaphyseal bone on the endosteal surface when dietary calcium had been made available to the LCD rats after lactation ceased. Unlike the rats fed the ACD after lactation, the rats continued on the LCD for the first 3 weeks postlactation failed to recover bone mineral, even though there was a marked decrease in resorbing surfaces of the femora as revealed by morphologic examination. When the diet was changed from the LCD to the ACD for the second 3 weeks postlactation (week 4-6), the bone mineral increased substantially. Overall, these results demonstrate the marked loss of bone during lactation, especially severe in rats fed a low-calcium diet, and the rapid postlactational recovery of bone when adequate dietary calcium was made available, even if the recovery had been delayed for the first 3 weeks by feeding a diet very low in calcium. PMID- 2316401 TI - IGF-I production by mouse osteoblasts. AB - Mouse osteoblasts contain and secrete insulinlike growth factor I (IGF-I), which can be measured by radioimmunoassay after separation from endogenous IGF-I binding activity. Our studies indicate that IGF-I is produced by all bone cell populations prepared by sequential digestion of mouse calvaria with collagenase and protease. Furthermore, relatively small amounts of IGF-I are cell associated, and IGF-I is recovered primarily in the cell medium after 24 h of culture. Basal IGF-I secretion is also density dependent, and secretion per cell is approximately 20-fold higher when cultures are inoculated at 0.125 versus 1.0 x 10(5) cells per cm2. Growth hormone increased the secretion of IGF-I only in cells released in the earlier stages of digestion. These growth hormone responsive populations were previously shown to differ from late released cells in that they show a lower expression of the osteoblastic phenotype, harbor more EGF receptors per cell, and have a higher proliferative response to low doses of exogenous IGF-I and EGF. These data reaffirm the presence of different subclasses of bone cells in populations obtained by sequential digestion of bone and suggest that growth hormone stimulates IGF-I secretion by immature osteoblasts. PMID- 2316402 TI - Iliac bone biopsies at the time of periarticular stress fractures during fluoride therapy: comparison with pretreatment biopsies. AB - We attempted to establish whether systemic changes in trabecular bone explain the development of stress fractures in the lower limbs during fluoride therapy for osteoporosis. To this end we compared transiliac bone biopsies obtained before treatment with those taken around the time of stress fractures after 14.3 +/- 10.9 (SD) months of therapy in six patients (group A). Biopsies from a comparable group of six patients without stress fractures at the time of the second biopsy (after 11.9 +/- 2.7 months of treatment) served for comparison (group B). The biopsies were processed undecalcified and examined by routine histomorphometry. The second biopsies did not show any significant improvement in mean bone volume or trabecular architecture. Although the second biopsies in group A had increased erosion surfaces (p less than 0.05) and greater osteoid volume (p less than 0.05), group B biopsies showed no difference in erosion surfaces but an increase in all osteoid parameters: osteoid volume (p less than 0.05), osteoid surface (p less than 0.05), and osteoid seam thickness (p less than 0.01). We reached the following conclusions: (1) the combination of increased erosion and replacement of removed bone by as yet unmineralized osteoid in the stress fracture group must have weakened bone and allowed the development of stress fractures. (2) Stress fracture patients may have mounted a less vigorous osteoblast response to fluoride than non-stress fracture patients. Under these conditions microfractures are likely to heal poorly and propagate to develop into full stress fractures. (3) Renal failure is a contraindication to fluoride therapy. PMID- 2316403 TI - Effects of weight lifting on bone mineral density in premenopausal women. AB - A group of 68 premenopausal women participated in a controlled 12 month exercise program. Two groups were matched according to age, body size (body mass index), and typical activity level. Data collection included bone mineral density (BMD) of the lumbar spine with dual-photon absorptiometry and of the os calcis with single-photon absorptiometry, lean body mass, urinary calcium/creatinine, and urinary gamma-carboxyglutamic acid (Gla). Subjects were given a daily 500 mg supplement of elemental calcium. There was no significant difference between groups in terms of diet, in urinary calcium/creatinine or Gla, or in lean body mass. The weight lifting group had a nonsignificant increase in mean lumbar BMD of 0.81% and the control group exhibited a nonsignificant decrease of 0.5%. However, a paired t-test revealed a significant change in the means in either group or as matched pairs. The relatively small change seen as a result of this modified Nautilus exercise program may prevent moderate weight lifting from being a practical answer for osteoporosis, even in a highly motivated population. PMID- 2316404 TI - Transfection of calcitonin gene regulatory elements into a cell culture model of the C cell. AB - Calcitonin gene expression in the TT cell line can be regulated by phorbol esters, cAMP, glucocorticoids, and 1,25-dihydroxyvitamin D3. To further study the regulation of this gene we have sequenced 1460 bases 5' to the start of calcitonin gene transcription. This DNA sequence contains cis consensus elements for both phorbol ester- and cAMP-responsive elements. To study the role of these elements, calcitonin 5' flanking DNA was coupled to the human growth hormone gene as a reporter and transiently transfected into TT cells, a human thyroid C cell line. Treatment of transfected TT cells stimulated a two- to fivefold increase in reported gene product expression, confirming the existence of functional cAMP- and phorbol ester-dependent enhancers within the calcitonin 5' flanking sequence. PMID- 2316405 TI - Plasma 24,25-dihydroxyvitamin D3 concentrations in X-linked hypophosphatemic mice: studies using mass fragmentographic and radioreceptor assays. AB - Previous studies have suggested that both plasma 24,25-dihydroxyvitamin D [24,25 (OH)2D] concentrations and renal 25-hydroxyvitamin D-24-hydroxylase activity are increased in mice with X-linked hypophosphatemia (Hyp mice). However, because the plasma levels of 24,25-(OH)2D seemed surprisingly high, we repeated these assays using two different techniques. Mass fragmentographic and radioreceptor assays were employed to compare the plasma concentrations of 25-hydroxyvitamin D (25 OHD) and 24,25-(OH)2D in normal mice with those in Hyp mice. These assays yielded 24,25-(OH)2D concentrations much lower than previously reported in mice (both normal and Hyp). The concentrations of 25-OHD3 and 24,25-(OH)2D3, determined by mass fragmentography, were lower in Hyp mice than in controls [25-OHD3, 9.7 +/- 0.4 versus 14.6 +/- 0.6 ng/ml, p less than 0.01; 24,25-(OH)2D3, 7.1 +/- 0.3 versus 10.4 +/- 0.4 ng/ml, p less than 0.01]. Plasma 25-OHD concentration was the main determinant of plasma 24,25-(OH)2D, and the ratio of 25-OHD3 to 24,25 (OH)2D3 obtained from mass fragmentographic measurements did not differ between the two groups (1.40 +/- 0.05 versus 1.36 +/- 0.03 ng/ml, NS in normal and Hyp groups, respectively). Separate measurement of plasma 25-OHD, 24,25-(OH)2D, and 25-OHD3-26,23-lactone by radioreceptor assay showed no difference between either plasma 24,25-(OH)2D, or the ratio of 25-OHD concentration to 24,25-(OH)2D concentration among Hyp and control animals. In neither study was plasma phosphate concentration related to the 25-OHD3:24,25-(OH)2D3 ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316406 TI - Monoclonal antibodies to ROS 17/2.8 cells recognize antigens, some of which are restricted to osteoblasts and chondrocytes. AB - We have raised a panel of 15 monoclonal antibodies (MAbs) recognizing cell surface antigens of the rat osteoblast-like cell line ROS 17/2.8. The MAbs were selected on the basis of preferential binding to ROS 17/2.8 cells compared to ROS 25/1 cells. Immunohistochemical studies of antigen localization on cryostat sections of rat calvaria, long bone, and soft tissues demonstrated that five of these MAbs, UBIM 1, 2, 3, 12, and 17, recognize antigens that are restricted to normal rat osteoblasts and chondrocytes. The antigens appear to be localized to the cell surface of the osteoblast, with no apparent staining of bone matrix in either undecalcified or decalcified sections. In vitro, these MAbs recognize cell surface antigens present on two additional cell lines, ROS 24/1 and Rat 2 cells, and on the adherent cell population cultured from rat long bone marrow. Of these MAbs, three (UBIM 1, 2, and 3) recognize high-molecular-weight antigens of Mr 200,000-225,000. This study has also identified cell surface antigens of ROS 17/2.8 cells that are not expressed by osteoblasts in vivo. MAbs UBIM 9 and 21 bind to marrow cells in long bone sections, to the 7-day-old nonadherent cell population from cultured marrow, and to lymphoid tissue in sections of spleen. Another four MAbs (UBIM 10, 11, 14, and 22) bind to a variety of cells and tissues both in vitro and in vivo. Studies of the interactions of this panel of MAbs with osteogenic tissues and cell lines may have an important impact on the understanding of osteoblast physiology. PMID- 2316407 TI - 24- and 26-homo-1,25-dihydroxyvitamin D3 analogs: potencies on in vitro bone resorption differ from those reported for cell differentiation. AB - It has been proposed that the stimulatory effects of 1,25-dihydroxyvitamin D on bone resorption may be mediated through actions on differentiation of marrow cells into monocytic osteoclast precursors. In human promyelocytic leukemia cells (HL-60), 24- and 26-homo-1,25-dihydroxyvitamin D3 and their delta 22 analogs and 24,24-dihomo-1,25-dihydroxyvitamin D3 are 10-fold more potent than 1,25 dihydroxyvitamin D3, and delta 22-24,24,24-trihomo-1,25-dihydroxyvitamin D3 is equipotent with 1,25-dihydroxyvitamin D3 in inducing differentiation into the monocytic phenotype. The effect of these 1,25-dihydroxyvitamin D3 analogous on resorption of fetal rat limb bones in vitro was determined in the present study. 1,25-Dihydroxyvitamin D3 was equipotent with 24-homo-1,25-dihydroxyvitamin D3, delta 22-24-homo-1,25-dihydroxyvitamin D3, 26-homo-1,25-dihydroxyvitamin D3, and delta 22-26-homo-1,25-dihydroxyvitamin D3 for in vitro bone resorption, whereas 24,24-dihomo-1,25-dihydroxyvitamin D3 and delta 22-24,24,24-trihomo-1,25 dihydroxyvitamin D3 were inactive. The failure of these analogs to show a higher bone-resorbing activity than 1,25-dihydroxyvitamin D3 were inactive. The failure of these analogs to show a higher bone-resorbing activity than 1,25 dihydroxyvitamin D3 provides evidence to suggest that the mechanism of 1,25 dihydroxyvitamin D3-induced bone resorption may not involve stimulation of monocytic cell differentiation. PMID- 2316408 TI - Situational factors in cigarette smoking. AB - Situational factors related to smoking behavior in the natural environment were studied. Six subjects smoked all cigarettes over 10 days with a portable, electronic recording device which measured a number of frequency and time-based features of smoking. Subjects also coded activities and internal states associated with each cigarette smoked. Across subjects, there were considerable differences in the distribution of cigarettes smoked across the activity and internal states categories. Within subjects, all subjects showed variation in measures of smoking topography (number of puffs/cigarette, mean puff duration, total puff time/cigarette) as a function of situational variables. It did not appear that pharmacological factors could fully account for the substantial situational differences found. The results suggest that different factors may be involved in the control of different aspects of smoking topography. PMID- 2316409 TI - Social influences approach to smoking prevention: the effects of videotape delivery with and without same-age peer leader participation. AB - This study tested the hypothesis that cigarette smoking adoption among adolescents could be suppressed by providing school-based videotape instruction for resisting social influences to smoke. The utilization of same-age peer leaders was also varied to test whether their participation in the classroom would enhance program effects. Seventh grade students (N = 540) from one junior high school in Southern California were randomly assigned by classrooms (N = 15) to: (a) videotape instruction, (b) videotape instruction plus peer leader involvement, or (c) survey-only. Seventh grade students (N = 234) in a second junior high school served as a measurement-only control. Assessments were conducted at the beginning and end of the academic year. Results revealed a marked suppression in the onset of both experimental and regular smoking among those students exposed to the pressure resistance training with peer leader involvement. Pressure resistance training without peer leader involvement produced a more variable and less powerful effect on students' smoking behavior. Data collected on students' use of alcohol and marijuana revealed a generalized suppression effect, albeit weaker than for tobacco, among those students exposed to the social resistance training with peer leader involvement. Results provide further encouraging support for the use of peer-led pressure resistance training in preventing adolescent drug use. PMID- 2316410 TI - Alcohol cue reactivity and ad lib drinking in young men at risk for alcoholism. AB - Individuals at high risk for alcoholism have been hypothesized to acquire alcoholic characteristics more rapidly than those at low risk. Two studies examined reactivity to alcohol cues, a phenomenon linked to craving for alcohol in clinical alcoholics, and ad lib drinking behavior in young men at varying risk for alcoholism. In Study 1, subjects exhibited increased autonomic and subjective responses during exposure to an alcohol beverage relative to a control beverage, suggesting that alcohol cue reactivity is not merely a clinical alcoholic phenomenon but also present in more moderate drinkers. This alcohol cue reactivity, however, was unrelated to risk status. Also, high-risk subjects exhibited greater nonspecific electromyographic and skin temperature reactivity, and higher baseline salivation volume than low-risk subjects. Of special note, ad lib alcohol consumption in Study 1 was correlated with subjects' self-report of craving during exposure to the alcoholic beverage. Study 2 attempted to replicate the baseline salivation finding but results were equivocal concerning the robustness of this effect. Also in Study 2, subjects exhibited decreased salivation volume following a placebo beverage and increased salivation volume following alcohol consumption. Studies 1 and 2 compared ad lib drinking behavior in high-risk and low-risk samples, but no group differences were found. PMID- 2316411 TI - A cognitive-behavioral approach to substance abuse prevention: one-year follow up. AB - This study presents one-year follow-up data from an evaluation study testing the effectiveness of a cognitive-behavioral substance abuse prevention approach which emphasizes the teaching of social resistance skills within the larger context of an intervention designed to enhance general social and personal competence. The follow-up study involved 998 eighth graders from 10 suburban New York junior high schools. Two schools were assigned to each of the following conditions (a) peer led intervention, (b) peer-led intervention with booster sessions, (c) teacher led intervention, (d) teacher-led intervention with booster sessions, and (e) control. The original intervention was implemented in the seventh grade; the booster intervention was implemented during the eighth grade. Results indicate that this type of prevention strategy, when implemented by peer leaders in the seventh grade and when additional booster sessions are provided during the eighth grade, can reduce tobacco, alcohol, and marijuana use. Similar effects are evident for females when the prevention program is implemented with fidelity by classroom teachers. Moreover, the prevention program is also capable of producing a significant impact on several hypothesized mediating variables. PMID- 2316412 TI - Parents' accuracy in estimating child weight status. AB - Mothers of 107 preschool children estimated their child's weight status, and the accuracy of these estimates was examined. The majority of mothers (72%) were accurate. Of those who were inaccurate, 83% had underestimated the child's weight status, whereas only 17% had overestimated. Mothers of heavier children were more likely to underestimate their child's weight status. PMID- 2316413 TI - Physical dependence and attributions of addiction among cigarette smokers. AB - Examination of the attitudes and attributions of cigarette smokers has differentiated smokers who believe their behavior is a "sickness" from those who believe they are "hooked." Among other things, the hooked smoker, more than the sick one, believes they are addicted and their chances of stopping smoking are poor. If there is a causal association between the attribution of addiction and perceived prospects of change, as this suggests, it could mean treatment and preventative programs stressing the addictive nature of cigarettes may be counterproductive. However, the present study, using a survey of 105 male and female smokers from the general population, suggests the attribution of addiction is related to a smoker's estimate of their chances of stopping only through a common association that each of these measures has with actual (not necessarily perceived) physical dependence. Caution is needed in the application of cognitive research when related physical measures have not been included in the research design. PMID- 2316415 TI - Adolescents' value images of smokers, ex-smokers, and nonsmokers. AB - Adolescents' value images of smokers, ex-smokers, and nonsmokers were investigated in a study of high school graduates. Overall, smokers were seen as being concerned with values related to personal enjoyment and autonomy. In contrast, nonsmokers were perceived as being more conventional, and more concerned with religious, interpersonal, and family values. Images of ex-smokers usually were intermediate, but resembled those of nonsmokers somewhat more than those of smokers. Interestingly, ex-smokers were perceived to place more importance on values relating to accomplishment and self-control than were either smokers or nonsmokers. In general, the value images were consistent among respondents who themselves were smokers, potential smokers, or nonsmokers. However, for a few values smokers and potential smokers had a more favorable image of smokers than did nonsmokers. Interestingly, males and females generally did not differ in their images of smokers, ex-smokers, and nonsmokers. Suggestions for prevention of adolescent smoking based on the value images are discussed. PMID- 2316414 TI - Relationship between nicotine tolerance questionnaire scores and plasma cotinine. AB - The Fagerstrom Tolerance Questionnaire (TQ) is often used in both research and treatment contexts to evaluate nicotine tolerance and physiological dependence in cigarette smokers. Recently, however, questions about its validity and its usefulness in comparison to other easily collected measures have been raised. In the present study, 100 male subjects reporting for experimental sessions (Sample I) and 50 male and female subjects entering a smoking cessation clinic program (Sample II) were administered the TQ and determinations of plasma cotinine during ad libitum smoking were made. TQ scores were found to be correlated with cotinine levels in both samples, and several of the individual items proved to have statistically significant discriminatory value. Other schemes for determining degree of dependence were considered and found not to be superior to the TQ. Suggestions for further refining the TQ are reviewed. PMID- 2316416 TI - Identification of nonalcoholic and alcoholic beers: effects of consumption practices and beer brand. AB - Because nonalcoholic beer provides sensory cues that simulate alcoholic beer, this beverage may be more effective than other placebos in contributing to a credible manipulation of expectancy to receive alcohol. The present experiment assessed the sensory identification of nonalcoholic and alcoholic beers. Subjects with higher beer consumption practices were more accurate than subjects with lower beer consumption practices in the identification of nonalcoholic beers. Brand of nonalcoholic beer affected the identification performance of subjects with lower beer consumption practices. PMID- 2316417 TI - Heavy drinking and its correlates in young men. AB - This study examined the drinking behavior of a sample of 98 college men and the relationship to drinking of a variety of subject variables. The subjects reported drinking an average of nearly eight days a month, about five drinks each time, and were intoxicated more than three times monthly. Nearly half reported having experienced two or more drinking-related adverse consequences within the past year and over a third were intoxicated four or more times monthly. Forty percent of the subjects could be described as problem drinkers. Illicit drug use and the disinhibition factor of the sensation seeking scale were the most consistent correlates of drinking behavior and its adverse consequences, although belonging to a fraternity, consuming alcohol/drugs before age 15, the Macandrew Alcoholism Scale score, and a family member having received alcoholism treatment were also found to be consistently associated with drinking in the subjects. Sociodemographic characteristics, physical health, mental health treatment, childhood behavior problems, adolescent antisocial behavior, and familial alcoholism were by and large not found to be related to drinking behavior. A stepwise multiple regression analysis revealed that five variables accounted for 51% of the total variance in drinking behavior. The significant predictors included a heavy drug use factor, a smoking factor, fraternity membership, drug/alcohol use before age 15, and having a family member who had received alcoholism treatment. Thus, four of the five significant predictor variables were reflective of drug use in the subject or his family. The findings underline the need for further prospective longitudinal research to understand the origins of problem drinking and its relationship to alcoholism. PMID- 2316418 TI - The ageing liver. PMID- 2316419 TI - Outcomes of care within a multiple-case study in the evaluation of the experimental National Health Service nursing homes. AB - This paper reports outcome data from a multiple-case study of the three experimental NHS nursing homes and six hospital wards undertaken as part of the evaluation of the experimental NHS nursing homes. While all subjects were very frail, NHS nursing home residents were found to be less frail than those in hospital wards. Significant differences in favour of the NHS nursing homes were found in the proportion of subjects engaged in meaningful activity during the mornings and afternoons, in the amount of activity and contact with others during the hour preceding lunchtime, and in amount of verbal interactions over lunchtime, particularly when choices were offered. These outcome data support the findings of other studies carried out as part of the evaluation that there is no evidence to imply that continuing-care accommodation should not be provided in NHS nursing homes. PMID- 2316420 TI - A re-validation of the Rivermead ADL scale for elderly patients with stroke. AB - The Rivermead ADL scale was developed for assessing activities of daily living in stroke patients but was not validated for elderly subjects. This study was designed to validate the scale for patients aged over 64 years. A series of 150 stroke patients was assessed on the scale, of whom 103 were aged over 64 years. The coefficients of reproducibility and 'scalability' were within acceptable limits both for patients aged under 65 and over 64 years. A revised order of assessment is suggested based on the order of difficulty of items. The two original household scales were combined to give an overall household scale which was validated as a unidimensional Guttman scale. PMID- 2316421 TI - Epileptic seizures in elderly people: aetiology and seizure type. AB - We have studied 342 patients who had their first seizures after the age of 60 years. The causes of seizures were identified in 305 patients (89%) with cerebrovascular disease accounting for 39%, head injury 21%, brain tumours 11%, metabolic disorders 7%, multifactorial aetiology 6%, and CNS infection 4%. The majority of patients (80%) had focal onset seizures that were secondarily generalized in 50%. PMID- 2316422 TI - Benign oesophageal stricture: the place of surgery in the management of elderly patients. AB - The results of surgery for benign oesophageal stricture in 53 consecutive cases referred to a sub-regional Cardiothoracic Unit are presented. The operations included retrograde dilatation and either total fundoplication or Allison repair, or an oesophageal resection with gastro-oesophageal anastomosis through a trans thoracic approach. Postoperative fatality was 9%. Most subsequent deaths were due to unrelated acute events with a 5-year survival rate of 62%. Sixty per cent were free from dysphagia and 82% led active and independent lives without support. Surgery offers an alternative to dilatation in elderly patients with oesophageal stricture. PMID- 2316424 TI - Transient neurological dysfunction and risk of stroke in an elderly English population: the different significance of vertigo and non-rotatory dizziness. AB - A sample of people aged 65 and over were interviewed at home and asked a series of questions aimed at identifying episodes of possible transient neurological dysfunction. During follow-up of respondents initially free from manifest cerebrovascular disease, no relationship was found between subsequent stroke and reported episodes of diplopia, transient numbness or weakness, non-rotatory dizziness or blackouts. There was an association of stroke with reported blurring or dimming of vision, statistically significant only for the sexes combined (relative incidence ratio 1.5), and a consistently increased risk in men and women reporting rotatory vertigo (relative incidence ratio 2.5). This relationship remained significant when adjusted for the association of rotatory vertigo with ECG evidence of heart disease. Thus rotatory vertigo is a risk factor for stroke but non-rotatory dizziness is not. Conversely a previous study of falling in the same population sample had shown an association with rotatory vertigo but not with non-rotatory dizziness. PMID- 2316423 TI - Acute renal failure: a study of elderly patients. AB - Two hundred and forty-six patients over the age of 65 years treated for acute renal failure (ARF) between 1960 and 1987 are reviewed. Although the fatality has apparently not changed over the duration of the study, it is possible to identify groups with a relatively good prognosis with renal replacement therapy. This particularly applies to patients with an underlying medical illness or with urological problems (excluding neoplasia). ARF following surgery with perioperative sepsis continues to carry a poor prognosis. We would recommend early referral of elderly patients with acute renal failure to a specialist unit, as a substantial proportion of survivors will regain normal renal function and quality of life. PMID- 2316425 TI - The contribution of computerized tomography to the differential diagnosis of confusion in elderly patients. AB - Two hundred and eighty elderly patients who were referred because of a principal problem of confusion were investigated by computerized tomography; 94% were suffering from a 'dementia syndrome' and unrecognized receptive dysphasia was the commonest problem in the remainder. One hundred and twenty-four patients were suffering from senile dementia of the Alzheimer type, and 79 from multi-infarct dementia. Space-occupying lesions (tumour, subdural haematoma or hygroma) were found in 32 (11%). Of the 25 with other intracranial and extracranial causes, 64% had potentially treatable lesions (PTL). In only four cases was no diagnosis made. PTL were found in 31% of 170 patients with a duration of confusion of less than a year compared with 1% of 110 patients with a longer duration. In 48 of the former group, confusion was an isolated phenomenon; 12 of these (25%) had a PTL, as had 27 of 88 with confusion and a focal neurological deficit (31%). All five patients with recognized seizures, and six of 15 of those with reduced alertness had PTL. Twenty of 37 patients with neurosurgical lesions underwent surgery. PMID- 2316426 TI - The effect of mild to moderate dementia on the Geriatric Depression Scale and on the General Health Questionnaire. AB - The Geriatric Depression Scale (GDS) and two versions of the General Health Questionnaire (GHQ 28 and corrected GHQ 28) were administered to 111 patients admitted to an acute geriatric medical unit. Depression and dementia were diagnosed by semi-structured interview using DSM III criteria. There was no statistically significant difference in the three scales between cognitively normal depressed patients and demented depressed patients. The three scales were sensitive indicators of depressive illness (greater than 90%), but the GHQ 28 and CGHQ 28 needed adjustment of their community-based threshold values. PMID- 2316427 TI - Oxybutynin and urinary incontinence. PMID- 2316428 TI - Risk factors for adverse drug reactions--epidemiological approaches. PMID- 2316429 TI - A twenty-year follow-up study on phenacetin abuse. PMID- 2316430 TI - Physician's compliance. PMID- 2316431 TI - Compliance with short-term high-dose ethinyl oestradiol in young patients with primary infertility. New insights from the use of electronic devices. AB - The objective of the study was to investigate patient compliance with ethinyl oestradiol therapy. Medication was prescribed to be taken in 20-micrograms doses four times daily for seven days. Oestrogens are prescribed for standardization of the cervical mucus before the sperm cervical-mucus penetration test (SCMPT) is performed. Relation of drug compliance with adverse drug reactions reported by the patients. The methodology used in this study was continual microprocessor based monitoring by means of the Medication Event Monitoring System, MEMSTM. Adverse drug reactions were recorded by means of standardized interviews. Investigations were carried out on thirty female patients, mean age: 28.8 years (range 21 to 36 years), with primary infertility, mean duration of infertility: 3.9 years (range 9 months to 8 years). The results showed that individual patients' compliance was remarkably variable, ranging from 14.3% up to 136%. The average compliance was 65%. Less than 30% of the prescribed doses were taken on schedule. Administration of oestrogens was effective in all but one patient. High cervical indices were documented irrespectively of the dose taken. In answer to the questionnaire, 24 out of 30 women reported side effects, of which 79% were rated by the patients as being mild. The lower the drug compliance was, the more adverse reactions were reported. In patients who took more than 65% of the drug, this inverse relationship was statistically significant (r = -0.71, p = less than 0.01). Our conclusion is that the empirically fixed daily dose of 80 micrograms of ethinyl oestradiol for seven days appeared to be too high in regard of the observed dose response, i.e. cervical mucus quality. A dose finding study, including compliance monitoring, seems to be reasonable. Within further studies, a simpler dosage regimen should also be taken into account. The observed association between patients' reports of adverse effects and drug compliance deserves further investigation. PMID- 2316432 TI - Risk factors as reflected by an intensive drug monitoring system. AB - Age and gender are often suspected to be risk factors predisposing to ADRs. Therefore the data obtained by the Heidelberg Intensive Drug Monitoring System were analysed for possible correlations between these two variables and the incidence of ADRs. Based on the medical records comprising the time period between 1980 and 1987 information was available on 70,500 admissions to the Heidelberg University Hospital, Department of Medicine. Age, gender, number of prescriptions and ADRs were analysed. The percentage of patients affected by ADRs rises with advancing age; however the number of prescribed drugs also increases. When the incidence of ADRs in various age groups was analysed in relation to prescription data, no effect of age could be found. In contrast there was a linear correlation between the overall incidence of ADRs (independent of age) and the number of prescriptions per patient (per single admission). These results clearly document that age does not seem to be relevant to the incidence of ADRs, but that the risk is related to the number of drugs prescribed to a particular patient. PMID- 2316433 TI - Time pattern of allergic reactions to drugs. AB - Generalized, allergic reactions to drugs show time patterns different from those based on pharmacological concepts. We distinguish three types of reactions: acute reactions (reaction time (RT): 0-60 minutes), subacute reactions (RT: 1-24 hours) and reactions of the latent type (RT: 1 day to several weeks). In this study, allergic reactions in the strict sense are supplemented by reactions considered to be based on intolerance or idiosyncrasy to aspirin, pyrazolones, paracetamol, NSAIDs, quinidine, iodine-containing contrast media and some as yet not understood reactions to local anaesthetics. Out of a total of 23,935 drug monitoring patients with 32,317 hospitalizations in the clinical divisions of internal medicine at three Swiss hospitals during the 1974-1987 period, 951 patients with 1,040 probably or definitely drug-related events of the selected type were recorded. Ultimately, 287 patients with 310 adverse drug reactions (ADRs) fulfilled our selection criteria and were classified into six groups of syndromes (Table 1). (Of the reactions described as maculopapular rash, unspecified rash and special exanthema, only the 159 reactions from the 1985-1987 period out of a total of 889 reactions of this type observed during the whole study period were included in our secondary evaluation.) The total number of 310 reactions (100%) showed the following RT distribution: 36 (11.6%) were of the acute type, 13 (4.2%) of the latent type, 12 (3.9%) could be interpreted as two distinct possible types of reaction to different drugs, and for 3 (1.0%) reactions, the type of reaction was indeterminable. The majority of reactions, 246 (79.4%), were of the subacute type starting within 24 hours of the last drug exposure. Among the 36 reactions of the acute type, 7 events of acute severe dyspnoea were observed which seemed to be as life-threatening as anaphylactic or anaphylactoid shock. These hospital-epidemiological data are of interest for focusing basic research and developing further principles of drug safety. PMID- 2316434 TI - Epidemiological screening for potentially carcinogenic drugs. AB - This paper describes a unique program for the systematic screening of commonly used prescription drugs for possible carcinogenic effects, by following up a large cohort of patients with computer-stored pharmacy data for incidence of cancer. Among the most interesting findings in recent analyses are an association of several antibiotics with subsequent lung cancer, and negative associations of prescribed vitamin E and diazepam with certain cancers. Analyses of additional data do not clearly indicate that these represent causal relationships to the drugs themselves. Also of interest is our continuing negative evidence regarding reserpine and metronidazole. The planned computerization of all pharmacies in our medical care program now serving over 2.2 million subscribers, should greatly increase our drug surveillance capabilities. PMID- 2316435 TI - Monitoring for adverse pregnancy outcomes related to drug exposure during pregnancy. PMID- 2316436 TI - Another house call. PMID- 2316437 TI - Lyme disease. PMID- 2316438 TI - Possible Lyme meningitis. AB - Lyme disease was first recognized in 1975 because of a cluster of patients with arthritis in the vicinity of Lyme, Connecticut. Subsequently the arthritis was linked with erythema chronicum migrans (88%), cardiac (8%), and nervous system diseases (11%). By 1983, the etiology of the disease had been confirmed as an infection caused by a spirochete, Borrelia burgdorferi, transmitted to man by the bite of a tick, Ixodes dammini. Then it became apparent that this was the same disease reported as far back as the 1920's, known in Europe as tick-borne meningeal polyneuritis, lymphocytic meningoradiculitis, or Bannwarth's syndrome. The usual presentation includes exposure to ticks or tick-infested areas of the Northeast, the characteristic rash, and then the neurological abnormalities, then the arthritis. This case is presented to illustrate the possible presence of the disease with no history of tick exposure, no travel to areas usually considered endemic and no characteristic rash. PMID- 2316439 TI - Legionella longbeachae. PMID- 2316440 TI - The retirement plan distribution decision. PMID- 2316441 TI - Space station technology applied to clinical care. PMID- 2316443 TI - Pharmacists in the physician's office. PMID- 2316442 TI - An RBRVS dissent. PMID- 2316444 TI - Will you make money? PMID- 2316445 TI - Value of pharmacy services: perceptions of consumers, physicians, and third party prescription plan administrators. AB - A study of patients, physicians, and third party prescription plan administrators was conducted to identify those pharmacy services they believe are important and valuable and to determine whether third party plan administrators would reimburse pharmacists for such services. Patient and physician focus groups indicated that both wanted personalized services related to medications. Physicians believe that pharmacists are talking to patients about their medications, whereas patients want more drug information but report that pharmacists are not always providing such information. A mail survey of 41 third party prescription plan administrators indicated they believe that pharmacy services are important to consumers and that pharmacists are already providing most of the services identified. One-third of the third party administrators said their companies would consider implementing a structured pharmacist incentive plan to improve enrollee satisfaction. Those whose companies would not most often gave "increased cost" as the reason. No clear relationship was shown between number or type of services and the incentive value offered. Providing administrators with evidence that enhanced pharmacy services will increase overall program cost savings may lead to implementation of pharmacy incentives. PMID- 2316446 TI - New drugs of 1989. PMID- 2316447 TI - Usefulness of two-dimensional echocardiography for immediate detection of myocardial ischemia in the emergency room. AB - Inappropriate discharge from the emergency room of patients with acute chest pain may have serious consequences. Regional asynergy is one of the first signs of myocardial ischemia and can be detected with 2-dimensional echocardiography (2 DE). This study determines the value of 2-DE in the emergency room for immediate detection of myocardial ischemia causing acute chest pain at the time the electrocardiogram was nondiagnostic. Forty-three patients (32 men and 11 women) with a normal or nondiagnostic electrocardiogram during acute chest pain were studied with 2-DE. Only patients without a previous myocardial infarction and without known coronary artery disease (CAD) were studied. The entire left ventricular wall was examined for presence of regional asynergy. Coronary angiography was performed within 3 weeks. Cardiac enzyme levels were measured serially to establish or rule out an acute myocardial infarction. Sensitivity of 2-DE for detection of myocardial ischemia was 88% (22 of 25), specificity 78% (14 of 18), negative predictive accuracy 82% (14 of 17) and positive predictive accuracy 85% (22 of 26). Sensitivity of 2-DE for detection of acute myocardial infarction was 92% (12 of 13), specificity 53% (16 of 30) and negative predictive accuracy 94% (16 of 17). Thus, 2-DE during pain and a nondiagnostic electrocardiogram can readily identify patients with CAD in the emergency room, and it can accurately rule out an acute myocardial infarction. PMID- 2316448 TI - Influence of myocardial infarction size on radionuclide and Doppler echocardiographic measurements of diastolic function. AB - To assess the relation between myocardial infarction size and diastolic function as measured by radionuclide ventriculography and Doppler echocardiography, 83 patients (aged 58 +/- 9 years) without significant valvular disease were studied 8 to 12 weeks after an acute myocardial infarction. Myocardial infarction size was measured by resting thallium-201 tomography. Peak early filling rate (in end diastolic volumes/s) was measured by gated blood pool scintigraphy. Doppler measures of mitral inflow were peak early (E) and atrial (A) filling velocities, slopes of E and A, percent E and A filling, E/A ratio and diastolic filling period. In univariate analyses, there was a significant inverse correlation between infarction size and the peak early filling rate (r = -0.59, p less than 0.001), and this remained significant (r = -0.63, p less than 0.0001) in an analysis that included 2 other determinants of the filling rate, age and diastolic filling period. Infarction size was directly correlated to the peak E velocity (r = 0.37, p less than 0.01), deceleration of E (r = 0.41, p less than 0.01) and percent E filling (r = 0.31, p less than 0.01), and was inversely correlated to peak A (r = -0.27, p less than 0.05) and percent A filling (r = 0.26, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316449 TI - Usefulness of angioplasty during acute myocardial infarction in patients with prior coronary artery bypass grafting. AB - The efficacy and risk of reperfusion strategies for myocardial infarction in patients with prior coronary artery bypass surgery are uncertain. In this study 72 patients with prior bypass grafting underwent direct percutaneous transluminal coronary angioplasty without antecedent thrombolytic therapy. There were 26 anterior and 46 inferior infarctions, including 11 patients (15%) in cardiogenic shock. The baseline ejection fraction was less than 40% in 47 (65%) patients. Angioplasty was successful in 41 of 48 (85%) vein grafts and 24 of 24 (100%) arteries (difference not significant) at 5.1 +/- 4.0 hours from the onset of symptoms (79% treated less than 6 hours). There were no urgent bypass operations, strokes or transfusions. In-hospital survival was 90% (nonshock 95% vs shock 64%, p less than 0.01). Symptomatic acute reclosure occurred in 1 patient. Predischarge coronary arteriography in 34 patients demonstrated continued vessel patency in 32 infarct vessels (94%), although 5 of these vessels were redilated for restenoses. Predischarge paired ventriculography in 26 patients showed an increase in ejection fraction from 44 +/- 16% to 51 +/- 18% (p less than 0.01). One- and 3-year actuarial survival was 89 and 87%. Thus, prior coronary surgery should not preclude reperfusion therapy by direct angioplasty, which can be accomplished with low procedural risk, improvements in ventricular function and excellent in-hospital and late survival. PMID- 2316450 TI - Effects of atrial pacing and dipyridamole administration on coronary hemodynamics of collateralized myocardial regions in stable angina pectoris. AB - Great cardiac vein blood flow by thermodilution and great cardiac vein oxygen saturation were measured in 14 patients with stable exertional angina and an angiographic pattern of complete occlusion of the proximal left anterior descending artery retrogradely filled by collateral vessels supplying still viable myocardium. Measurements were obtained under control conditions, at peak atrial pacing and after dipyridamole administration (0.56 mg/kg intravenously over 4 minutes). Both stress tests induced ischemic electrocardiographic changes in all patients, but dipyridamole administration resulted in greater ST-segment depression in 11 patients (1.6 +/- 0.5 vs 2.4 +/- 1.6 mm, p less than 0.05) and transient ST-segment elevation in 3 patients. Dipyridamole provoked ischemia at a lower value of rate-pressure product (145.3 +/- 30.6 vs 202.9 +/- 36.6 beats/min . mm Hg . 10(-2), p less than 0.0005) and anterior region myocardial oxygen consumption (9.32 +/- 4.76 vs 11.39 +/- 3.91 ml/min, p less than 0.05), despite a greater increase in great cardiac vein flow (139.4 +/- 45 vs 93 +/- 27.4 ml/min, p less than 0.0025) and a greater decrease in the calculated index of anterior region coronary resistance (0.87 +/- 0.27 vs 1.46 +/- 0.43 mm Hg/ml/min, p less than 0.0005). Moreover, great cardiac vein oxygen saturation increased more significantly during dipyridamole-induced ischemia than at peak pacing (63 +/- 12 vs 35 +/- 8%, p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316452 TI - Possible role of coronary artery spasm in unexplained syncope. AB - Coronary spasm provocation by intracoronary methylergonovine was performed in 14 patients (8 men and 6 women, mean age 56 +/- 6 years) with syncope that remained unexplained despite neurologic and noninvasive cardiac evaluations. Electrophysiologic testing was also performed in 6 of 14 patients. No patient had structural heart disease or significant fixed stenosis of greater than or equal to 75% in the coronary arteries. Six patients had no history of chest pain even when they developed syncope. Serious arrhythmia was documented in 2 patients, cardiac standstill in 1 and complete atrioventricular block in the other. Coronary spasm was induced in 9 patients using the methylergonovine provocation test. Multivessel spasms were found in 3 patients. Coronary spasm was induced in the artery supplying the inferior wall in 7 of 9 patients with positive results. In 4 of 9 patients who had a positive result, there was no prior history of chest pain. In 1 patient, whose electrocardiogram was recorded during syncope, cardiac standstill was documented and cardiac standstill and syncope also occurred during the provocation test. Monomorphic ventricular tachycardia was not induced by the electrophysiologic study. These results suggest that coronary spasm is involved in unexplained syncope. PMID- 2316451 TI - Magnesium deficiency detected by intravenous loading test in variant angina pectoris. AB - To study whether magnesium (Mg) deficiency is present in patients with variant angina, 24-hour Mg retention of low dose Mg (0.2 mEq/kg lean body weight) administered intravenously over 4 hours in 20 patients with variant angina was examined. No patient had received calcium antagonists before or during the study. All had attacks of chest pain associated with ST elevation on electrocardiograms. Twenty-one subjects without ischemic heart disease were studied as control subjects. Ten patients with variant angina were restudied 10 to 529 days (mean 235 +/- 30) after the treatment with calcium antagonists (diltiazem 120 to 240 or nifedipine 40 to 80 mg/day), which resulted in complete suppression of anginal attacks. The mean serum Mg concentrations in the patients with variant angina and the control subjects were 2.1 +/- 0.05 and 2.1 +/- 0.03 mg/dl, respectively (difference not significant). However, 24-hour Mg retention in the patients with variant angina was 60 +/- 5%, while that in the control subjects was 36 +/- 3% (p less than 0.001), suggesting that Mg deficiency is present in at least some patients with variant angina. The mean serum Mg concentrations before and after calcium antagonist treatment in 10 patients with variant angina were 2.1 +/- 0.09 and 2.1 +/- 0.07 mg/dl, respectively (difference not significant). However, 24 hour Mg retention decreased significantly (p less than 0.01) from 60 +/- 6 to 34 +/- 7% after the treatment. There is Mg deficiency in many patients with variant angina and it is corrected after treatment with calcium antagonists. PMID- 2316453 TI - Prognostic significance of silent myocardial ischemia on a thallium stress test. AB - The clinical significance of silent ischemia is not fully known. The purpose of this study was to determine whether the presence or absence of angina during a thallium stress test positive for ischemia was independently predictive of an adverse outcome. Two hundred thirty-four consecutive patients with ischemia on a thallium stress test were identified. Ischemia was defined as the presence of defect(s) on the immediate postexercise scans not in the distribution of prior infarctions that redistributed on 4-hour scans. During the test 129 patients had angina, defined as characteristic neck, jaw, arm, back or chest discomfort, while the remaining 105 patients had no angina. Follow-up ranged from 2 to 8.2 years (mean 5.2 +/- 2.1) and was successfully obtained in 156 patients. Eighty-two of the 156 patients had angina (group A) and 74 had silent ischemia (group S). Group A patients were significantly older (62 +/- 8 vs 59 +/- 8 years, p less than 0.05). There was no significant difference between the 2 groups in terms of sex, history of prior infarction or presence of left main/3-vessel disease. A larger percentage of patients in group A were receiving beta blockers (60 vs 41%, p less than 0.05) and nitrates (52 vs 36%, 0.05 less than p less than 0.10). There was a large number of cardiac events (myocardial infarction, revascularization and death) in both groups (37 of 82 [45%] in group A; 28 of 72 [38%] in group S) but no statistically significant difference between the groups. Similarly, life-table analysis revealed no difference in mortality between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316454 TI - Influence of ventricular function and presence or absence of coronary artery disease on results of electrophysiologic testing for asymptomatic nonsustained ventricular tachycardia. AB - One hundred ten patients with asymptomatic nonsustained ventricular tachycardia (VT) were evaluated prospectively to assess the value of electrophysiologic testing. This testing consisted of up to 3 extrastimuli delivered during 3 drive cycle lengths from 2 right ventricular sites. A positive study was defined as monomorphic VT lasting 30 seconds or requiring cardioversion. Patients with a positive study were treated, and serial drug testing was done. An event during follow-up was sustained VT or cardiac arrest. The mean follow-up was 15 months. Of 57 patients with an ejection fraction greater than or equal to 40%, 6 had a positive electrophysiologic test with 1 event and 51 had a negative test with 1 event. Twenty-eight patients had an ejection fraction less than 40% and coronary artery disease: 14 had a positive test with 1 event, and 14 had a negative test with 3 events. Twenty-five patients had an ejection fraction less than 40% and no coronary artery disease: 1 had a positive test with no events, and 24 had a negative test with 8 events. Only ejection fraction and congestive heart failure class were found to be independent predictors of outcome. Patients with an ejection fraction greater than 40% had low inducibility (11%), had few events (3.5%) and did not require electrophysiologic testing. In patients with an ejection fraction less than 40% and coronary artery disease, inducibility was high (50%) and a negative study was of no value. Patients with an ejection fraction less than 40% and no coronary artery disease had low inducibility (4%), had frequent events (33%) and did not benefit from electrophysiologic testing. PMID- 2316455 TI - Relation of prognosis in sick sinus syndrome to age, conduction defects and modes of permanent cardiac pacing. AB - A large population of sick sinus syndrome (SSS) patients was analyzed to determine whether age of patients, presence of conduction disturbances and mode of permanent pacing are related to the occurrence of supraventricular tachyarrhythmias, cerebral embolism and cardiac mortality. Three hundred thirty nine patients permanently paced (135 AAI, 79 DDD, 125 VVI) because of SSS were followed for a mean period of 5 years (range 2 to 10). Patients were divided into 4 groups according to age (less than 70 or greater than 70 years) and the presence or absence of an associated conduction disturbance. Sixty-eight percent of VVI, 55% of AAI and 40.5% of DDD patients were greater than 70 years of age. In the VVI and DDD groups a conduction disturbance was present in 67 of 204 (33%) patients; conduction disturbances were more common in patients greater than 70 years old (46 of 111, 41%) than in those less than 70 years old (21 of 93,22%). The Wenckebach threshold (greater than 140 beats/min) remained unchanged during the follow-up period in 82% of AAI patients. In 9% of these patients, the Wenckebach threshold showed some degree of deterioration, but only in 2 patients was it less than 100 beats/min (1.5%). Spontaneous second-degree atrioventricular block was observed in 7 patients (5%); it disappeared in 6 of these patients when drug therapy was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316456 TI - Defective myocardial carnitine metabolism in congestive heart failure secondary to dilated cardiomyopathy and to coronary, hypertensive and valvular heart diseases. AB - Reduced myocardial carnitine concentrations in the explanted heart and elevated plasma levels have been found in patients undergoing heart transplant for end stage congestive heart failure (CHF). To evaluate a possible loss of myocardial carnitine in less severe stages of CHF, total myocardial carnitine levels were compared in right ventricular endomyocardial biopsies from 28 patients with mild, moderate and severe dilated cardiomyopathy, 8 patients with CHF of different origin and 13 normal control subjects. If possible, free myocardial carnitine and free and total plasma carnitine were also determined. For the first time, myocardial carnitine levels have been measured in endomyocardial biopsies from 13 normal human hearts (control values: 9.9 +/- 0.8 nmol/mg noncollagen protein). In comparison with these control values, total myocardial carnitine was significantly reduced in patients with dilated cardiomyopathy (6.1 +/- 0.5 nmol/mg noncollagen protein, p less than 0.0001), and CHF of other origins (6.6 +/- 1.1 nmol/mg noncollagen protein, p less than 0.02). Free myocardial carnitine concentrations in dilated cardiomyopathy (4.6 +/- 0.4 nmol/mg noncollagen protein) and CHF of different origin (4.4 +/- 0.5 nmol/mg noncollagen protein) were also significantly different from control values (control values: 9.7 +/- 0.7 nmol/mg noncollagen protein, p less than 0.0001 and p less than 0.005 for both groups). The loss of free and total myocardial carnitine was comparable in dilated cardiomyopathy and CHF due to other diseases. In contrast, plasma free and total carnitine levels in the CHF patients were significantly elevated (67 +/ 5.5 mumol/liter, control values 41 +/- 3.7 mumol/liter, p less than 0.005). Alterations in myocardial carnitine metabolism represent nonspecific biochemical markers in CHF with yet unknown consequences for myocardial function. PMID- 2316457 TI - Balloon dilatation of the stenosed aortic valve: how does it work? Why does it fail? AB - The hemodynamic changes that may occur in patients undergoing aortic balloon valvuloplasty were examined in the circulatory model. Four conclusions were reached. (1) Significant transvalvular pressure gradients appear only if the orifice is severely narrowed. (2) The magnitude of this gradient is highly flow dependent. (3) At critical narrowings, minute alterations in orifice size may induce most significant changes in the transvalvular gradient. (4) In low flow states significant gradients appear only if the stenosis is extreme. In patients with aortic stenosis, especially those with failing hearts and low cardiac output, the pressure gradient may be effectively decreased by minimal dilatation of the aortic orifice. These patients, however, remain in jeopardy because recurrent narrowing may cause a gradient incompatible with life. PMID- 2316458 TI - Comparison of proximal left anterior descending and circumflex coronary artery dimensions in aortic valve stenosis and hypertrophic cardiomyopathy. AB - To examine the "adequacy" of basal coronary flow in ventricular hypertrophy, the relation between proximal coronary artery dimensions and regional ventricular mass in aortic valve stenosis (AS) and hypertrophic cardiomyopathy (HC) was evaluated. Coronary artery size was determined by quantitative coronary arteriography while global/regional ventricular mass was calculated using computer-processed biplane 2-dimensional echocardiography. In comparison to 18 "normal" subjects, left anterior descending coronary dimensions were significantly larger in those with hypertrophy (normal 3.32 +/- 0.54, AS 3.82 +/- 0.71, HC 4.72 +/- 0.81 mm, p less than 0.05), with progressive increases in left anterior descending/circumflex coronary diameter ratios (normal 1.04 +/- 0.14, AS 1.18 +/- 0.19, HC 1.25 +/- 0.31, p less than 0.01). Compared to the AS group, indexed anteroseptal mass was greater in the HC subjects (AS 40.9 +/- 8.9 vs HC 72.1 +/- 21 g/m2, p less than 0.001). Both septal width/left anterior descending coronary diameter ratios (AS 3.61 +/- 1.06 vs HC 4.85 +/- 1.17 mm/mm, p less than 0.05) and indexed anteroseptal mass/left anterior descending coronary diameter ratios (AS 11.2 +/- 3.0 vs HC 15.6 +/- 3.4 g/m2/mm, p less than 0.01) were greater in HC subjects. Increased coronary dimensions were observed in both AS and HC, with the greatest changes noted within the left anterior descending distribution in HC, but when analyzed with respect to regional ventricular mass, these subjects demonstrated relative "inadequate" enlargement in coronary artery diameters. Underdeveloped epicardial coronary arteries may contribute to anteroseptal myocardial ischemia, with resultant angina pectoris, increased ventricular ectopic activity and sudden death in HC. PMID- 2316459 TI - Results of the Valvuloplasty and Angioplasty of Congenital Anomalies Registry. PMID- 2316460 TI - Balloon pulmonary valvuloplasty: results of the Valvuloplasty and Angioplasty of Congenital Anomalies Registry. AB - Eight hundred twenty-two balloon pulmonary valvuloplasties were reported to the Valvuloplasty and Angioplasty of Congenital Anomalies Registry. Before and after systolic outflow gradients were recorded in 784 valvuloplasties, and the gradient decreased from 71 +/- 33 to 28 +/- 21 mm Hg. The sites of residual obstructions could be ascertained in 196 patients. In these, the total systolic outflow gradients decreased from 85 +/- 41 mm Hg to 33 +/- 27 mm Hg. Of this total residual gradient, 16 +/- 15 mm Hg was transvalvar and 18 +/- 24 mm Hg was infundibular. The degree to which infundibular obstruction subsequently resolved was not determined in this study. The procedure was less effective in reducing outflow gradients in patients with dysplastic valves with or without Noonan's syndrome. There were 5 major complications (0.6%), including 2 deaths (0.2%), a cardiac perforation with tamponade (0.1%) and 2 tricuspid insufficiencies (0.2%). There were 11 minor complications (1.3%) and 21 incidents (2.6%). The incidence of major complications, minor complications and incidents was inversely related to age; it was substantially higher in infants and, in particular, neonates. Balloon pulmonary valvuloplasty is a safe and effective method of lowering pulmonary outflow gradients in infants, children and adults. Small transvalvar and varied infundibular gradients commonly are present at the end of the procedure. Assessing the full effect of the procedure requires intermediate-term follow-up and assessing the duration of relief requires long-term follow-up. PMID- 2316461 TI - Balloon aortic valvuloplasty: results of the Valvuloplasty and Angioplasty of Congenital Anomalies Registry. AB - Data from 204 children and infants who underwent aortic balloon valvuloplasty between 1982 and 1986, reported to the Valvuloplasty and Angioplasty of Congenital Anomalies Registry, were reviewed. Valvuloplasty was successful in 192 of 204 children, reducing the peak systolic left ventricular ejection gradient from 77 +/- 2 to 30 +/- 1 mm Hg, p less than 0.001. The same degree of aortic stenosis gradients reduction was noted in both the 38 children under 1 year of age and in the 166 children over 1 year of age. Significant complications included death, aortic regurgitation and femoral artery thrombosis or damage. The incidence of these complications correlated with the age of the child, the ratio of valvuloplasty balloon size/anulus size, or both. The data suggest that percutaneous balloon valvuloplasty provides effective acute relief of valvar aortic stenosis in both infants and children. However, long-term follow-up data are necessary before balloon valvuloplasty can be established as a treatment of choice for congenital valvar aortic stenosis. PMID- 2316462 TI - Balloon angioplasty for the treatment of native coarctation: results of Valvuloplasty and Angioplasty of Congenital Anomalies Registry. AB - Data on dilation of 141 native coarctation procedures in 140 patients between 3 days and 29 years of age were submitted to the Valvuloplasty and Angioplasty of Congenital Anomalies (VACA) Registry. Fifteen patients were less than 4 weeks old, 15 between 1 month and 12 months old and 110 patients over 1 year old. The immediate results confirmed that native coarctations could be effectively dilated in both infants and older children. The data do not support any conclusions concerning balloon size relative to results or complications. There were 24 complications (17%) reported with 1 death after 3 days and after intervening surgery in an infant with associated persistent ductus arteriosus. There were 2 early and 6 late "aneurysms" reported after the coarctation dilations with insufficient immediate and no long-term information about the significance of these. The VACA Registry data suggest that dilation of native coarctations can be performed effectively and relatively safely but do not answer whether this procedure should be performed. PMID- 2316463 TI - Balloon angioplasty--branch pulmonary artery stenosis: results from the Valvuloplasty and Angioplasty of Congenital Anomalies Registry. AB - Balloon angioplasty for branch pulmonary artery stenosis was reported from 27 institutions to the Valvuloplasty and Angioplasty of Congenital Anomalies Registry. One hundred eighty-two procedures were performed in 156 patients ranging in age from 0.2 to 46.2 years (mean 7.7). Short-term angiographic appearance, hemodynamic results and immediate complications were recorded. Vessel dimension at the site of stenosis increased from 4.5 +/- 2.0 (mean +/- standard deviation) to 6.8 +/- 3.0 mm (p less than 0.001) with greater increases in vessel dimension at the site of stenosis if the balloon diameter was greater than 3 X the original dimension of the stenosis. There was no significant benefit related to age or prior surgical intervention. The mean peak systolic pressure gradient was reduced from 49 +/- 25 to 37 +/- 26 mm Hg (p less than 0.001) and pressure proximal to the stenosis decreased from 69 +/- 25 to 63 +/- 24 mm Hg (p less than 0.001). Complications occurred in 21 patients and included vessel rupture and death in 2 patients, vessel perforation or rupture with survival in 3, cardiac arrest and death in 1, paradoxical embolism and death in 1 and low output and death in 1. Balloon angioplasty for branch pulmonary artery stenosis increases vessel dimension at the site of stenosis, reduces systolic pressure gradient and to a minor degree, reduces proximal pressure. Long-term outcome and potential complications are as yet uncertain. PMID- 2316464 TI - Balloon dilation of miscellaneous lesions: results of Valvuloplasty and Angioplasty of Congenital Anomalies Registry. AB - Data on 111 lesions, in addition to pulmonary valve, aortic valve, branch pulmonary stenosis, native coarctation and recoarctation, were submitted to the Valvuloplasty and Angioplasty of Congenital Anomalies Registry. Because there was a very heterogenous group of lesions both in types of lesions and techniques of dilation, only minimal data can be offered concerning the efficacy of the dilation of any or all of these lesions. The registry data do, however, demonstrate the safety of these dilations compared to alternative surgical therapy. PMID- 2316466 TI - Cause of acute myocardial infarction late after successful coronary artery bypass grafting. PMID- 2316465 TI - Assessment of the hemodynamic response to acetyl-strophanthidin by Doppler echocardiography in normal subjects and in those with coronary artery disease or idiopathic dilated cardiomyopathy. AB - The effect of acetyl-strophanthidin, a rapidly acting digitalis-like drug, was measured on peak flow velocity, stroke distance (an index of stroke volume) and minute distance (an index of cardiac output), determined by Doppler echocardiography in 21 subjects with a wide range of left ventricular ejection fractions (12 to 89%, average 47%). For the total study group, peak flow velocity increased from 99 +/- 10 to 110 +/- 13 cm/s (p less than 0.01), and stroke distance increased from 15.1 +/- 3.2 to 16.8 +/- 3.1 cm (p less than 0.01). Minute distance remained unchanged: 1,093 +/- 168 cm before and 1,129 +/- 187 cm after acetyl-strophanthidin (difference not significant). Improvement in Doppler parameters of forward blood flow was significantly (p less than 0.001) greater in subjects with left ventricular ejection fractions less than 60% (+17% for peak flow velocity, +22% for stroke distance and +15% for minute distance) than those with left ventricular ejection fractions greater than or equal to 60% (+4% for peak flow velocity, +2% for stroke distance and -8% for minute distance). These data suggest that Doppler echocardiography is a useful method to assess the efficacy of acute digitalis administration in improving forward blood flow. PMID- 2316467 TI - Usefulness of echocardiographic left ventricular ejection fraction and silent myocardial ischemia in predicting new coronary events in elderly patients with coronary artery disease or systemic hypertension. PMID- 2316468 TI - An angiographic and histologic study of cocaine-induced chest pain. PMID- 2316469 TI - Evaluation of Fontan's operation by magnetic resonance imaging. PMID- 2316470 TI - Endomyocardial biopsy in cardiac transplant recipients using the femoral venous approach. PMID- 2316471 TI - Left ventricular diastolic volume changes by exercise radionuclide ventriculography in normal subjects and in patients with coronary arterial narrowing. PMID- 2316472 TI - Rapid bolus magnesium sulfate for supraventricular tachycardia. PMID- 2316473 TI - Acquired bicuspid aortic valves. PMID- 2316474 TI - A symposium: Evolving issues in the treatment of hypercholesterolemia. June 18, 1989, Washington, D.C. Proceedings. PMID- 2316475 TI - Lipid-lowering therapy after an atherosclerotic event. PMID- 2316476 TI - Diffuse extent of coronary atherosclerosis in fatal coronary artery disease. AB - In 4 subsets of patients with coronary artery disease, the amounts of narrowing of the 4 major epicardial coronary arteries were compared (left main, left anterior descending, left circumflex and right) by atherosclerotic plaques. Among 129 patients studied at necropsy, an average of 2.7 of the 4 arteries were narrowed greater than 75% in cross-sectional area at some point; in control subjects, narrowing was seen in an average of 0.7 arteries. Patients with unstable angina pectoris had a greater incidence of narrowing (3.2 arteries) than did patients with sudden coronary death (2.8), acute myocardial infarction (MI) (2.7) or healed MI (2.3). Each of the 4 major arteries was divided into segments 5 mm in length, and histologic sections were prepared and stained by the Movat method. A total of 6,461 segments were analyzed from the 129 patients and 1,849 from the 40 controls. In the 129 patients, 35% of the 5-mm segments were narrowed 75 to 100% in cross-sectional area (compared with 3% in control subjects). The group with unstable angina had the highest percentage (48%) of severely narrowed segments compared with the groups with sudden coronary death (36%), acute (34%) and healed MI (31%). Only 8% of the 6,461 segments were narrowed less than or equal to 25% in cross-sectional area, and virtually none of the 6,461 segments was normal; thus, 92% of the coronary segments were narrowed greater than 25% in cross-sectional area by atherosclerotic plaque alone. Among patients with fatal coronary artery disease studied at necropsy, therefore, the atherosclerotic process is severe and diffuse in the major epicardial coronary arteries. PMID- 2316477 TI - Can atherosclerotic lesions regress? Angiographic evidence in humans. AB - Evidence that atherosclerotic lesions can regress is derived from autopsy findings in starved human populations, animal-model studies of induced atherosclerosis, and clinical trials using angiography. Three angiographic trials, with a total of 317 subjects, have demonstrated stabilization of lesions. One of these trials has revealed clear evidence of lesion regression. PMID- 2316478 TI - Thirtieth annual meeting. The American Society for Clinical Nutrition, Inc. May 3, 4, and 5, 1990, Washington, DC. Abstracts. PMID- 2316479 TI - Intraoperative and external beam radiotherapy in invasive bladder cancer: pathological findings following cystectomy. AB - The pathological findings observed following intraoperative radiotherapy (IORT) boost (15Gy) to the whole bladder, external beam fractionated irradiation (46Gy in 5 weeks), and planned radical cystectomy in patients with deep invasive bladder carcinoma are analyzed. Clinical pretreatment stage of disease was T3 (16 cases) and T4 (two cases). No evidence of residual tumor (pT0) was demonstrated in 11 cystectomy specimens (61%) and residual tumor (pT+) was observed in seven (39%). Toxicity and complications related to the treatment approaches were minor and reversible. It is concluded that IORT is a feasible boosting modality in the management of invasive bladder cancer, able to induce high rates of pT0 cystectomy specimens, and might be considered as a valuable technique for organ preservation treatment programs. PMID- 2316480 TI - Teniposide (VM-26) in patients with non-squamous-cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group. AB - Twenty-three evaluable patients with non-squamous-cell carcinoma of the cervix were treated with teniposide 100 mg/m2 per week administered as a 30-60 min infusion. Escalations of 20 mg/m2 per week to a maximum dose of 160 mg/m2 were performed in patients without toxicity. Thirteen of the 23 patients had no prior chemotherapy. One patient had a partial response (95% confidence intervals for response less than or equal to 19%). Toxicity was minimal. Seven patients had white blood cell counts of less than 2,000/mm3 but only one had less than 1,000/mm3. No patients had platelet counts less than 50,000/mm3, and no bleeding or septic episodes were noted. Two patients had mild nausea and seven had mild nausea and vomiting. Teniposide displays no major activity in patients with non squamous-cell cervical cancer. PMID- 2316481 TI - Monoclonal antibodies in the treatment of metastatic carcinoma to the liver: report of a pilot study including leukopheresis. AB - Thirteen patients with metastatic liver carcinoma were treated with hepatic irradiation, leukopheresis and monoclonal antibodies to test the tumoricidal effects of murine 17-1A immunoglobulin G (IgG) Mab. A significant increase in survival for this group of patients was identified. PMID- 2316482 TI - Benzylidene-glucose: no effect after all? AB - Several promising reports on the treatment of human cancer with various benzaldehyde derivatives have been published during the last decade. The present phase II study was performed to investigate whether the rather sensational results of one such derivative, benzylidene-D-glucose (BG), could be confirmed. The study included 14 patients with metastases from adenocarcinomas of the colon and rectum. The patients were treated with BG according to the recommended regimen for 8 weeks, after which tumor response was evaluated. Neither clinical tumor regression nor side effects were observed. The present study does not confirm the extremely good results previously reported by others. We conclude that BG is not an active agent in colorectal cancer. PMID- 2316483 TI - Electrochemical treatment of cancer. III: Plasma pharmacokinetics of adriamycin after intraneoplastic administration. AB - Plasma pharmacokinetics of Adriamycin (doxorubicin) has been studied after intraneoplastic administration during electrochemical treatment to patients with lung cancer that is noncurable with radiotherapy, surgery, or chemotherapy. Intraneoplastic administration of Adriamycin via the anode resulted in a dramatic change of the pharmacokinetic pattern in plasma as compared with what has been previously observed after intravenous administration. A fivefold reduction of the area under the plasma concentration time curve and a 25-fold reduction of the maximum plasma concentration was observed. PMID- 2316484 TI - Electrochemical treatment of cancer. IV: Leukocyte and platelet counts in peripheral blood after electrochemical treatment of solitary lung neoplasms. AB - The effects on hematological parameters in peripheral blood was measured by electronic cell counting after electrochemical treatment (n = 11), after electrochemical treatment with concomitant intraneoplastic injection of the chemotherapeutic agent doxorubicin (Adriamycin) (n = 13), and after electrochemical treatment with concomitant intravenous infusion of Adriamycin (n = 2). After treatment, a reduction in lymphocyte count (p less than 0.01) and an increase in total leukocyte count (p less than 0.01) was observed. There was a trend that during treatment the platelet count was reduced. PMID- 2316485 TI - Combination metoclopramide and diphenhydramine short infusion for prevention of chemotherapy-induced emesis. PMID- 2316486 TI - Cerebral metastases in pleural mesothelioma. PMID- 2316487 TI - Evaluation of trilostane plus hydrocortisone in women with metastatic breast cancer and prior hormonal therapy exposure. AB - Trilostane, which causes a perturbation of adrenal steroidogenesis, was studied in combination with hydrocortisone in 32 women with progressive metastatic breast cancer. Trilostane was administered orally at a dosage level of 240 mg four times daily after escalation over the first 10 days from 60 mg four times daily. Hydrocortisone was given orally at doses of 10 mg at 8 a.m. and 5 p.m. and 20 mg at bedtime. Patients must have been postmenopausal (81%) or previously castrated (19%), had a response to the hormonal treatment just prior to study (81%) or a positive estrogen receptor at time of entry on study (41%), and a measurable indicator lesion. The number of prior hormonal therapies was 1 in 19 patients (59%), 2 in 12 patients (38%), and 3 in 1 patient (3%), respectively. Twelve patients (38%) achieved an objective response, and a 95% confidence interval for this result is from 21 to 56%. The median time to disease progression was 140 days, median duration of response was 278 days, and median survival was 556 days. Common toxicities included lethargy, lightheadedness, diarrhea, and abdominal discomfort. Eleven patients required a dosage reduction, usually because of gastrointestinal side effects, and one additional patient had the trilostane discontinued because of leukopenia. We conclude that the combination of trilostane plus hydrocortisone appears to have definite antitumor activity in women with metastatic breast cancer who have characteristics favorable for response to hormonal therapy. PMID- 2316489 TI - The changing field of hematopathology. Tradition versus technology. PMID- 2316488 TI - Combination chemotherapy with oral etoposide plus intravenous cyclophosphamide in liver metastases of breast cancer. AB - Sixteen patients with hepatic metastases of histologically documented breast cancer were treated with etoposide (VP 16-213) and cyclophosphamide. Previously, 6 had shown relapse in the liver after adjuvant chemotherapy, 2 had failed to respond to another chemotherapy combination, and 8 had never undergone chemotherapy. Fifty percent responded to treatment, including 1 complete remission and 7 partial responses. Median survival was 16 months and median duration of response was 13 months. All patients showed alopecia and moderate leukopenia; 13 experienced moderate gastrointestinal toxicity; there was 1 mild case of anemia and 1 case of moderate hemorrhagic cystitis. This study suggests that the combination of VP 16-213 and cyclophosphamide is a well-tolerated and effective treatment in advanced breast cancer patients with liver metastases. PMID- 2316490 TI - Pathology patterns. ASCP commentary on the environment of laboratory medicine. PMID- 2316491 TI - New technology in laboratory medicine. A call for pathologists to lead the march. AB - Several new technologies are impacting the practice of pathology. Appropriate clinical uses must be defined and standards established. It is vitally important that pathologists play the leadership role in incorporating new diagnostic techniques in the clinical laboratory. To do so may require new knowledge and skills. Pathology associations must support the needs of their members by providing avenues for education and training in new technologies applicable to pathology practice. PMID- 2316492 TI - The paradox of high risk of stroke in populations with low risk of coronary heart disease. AB - The "paradoxical" occurrence of high rates of stroke and low rates of coronary heart disease observed in Asian and other populations has been examined using accumulated clinical and autopsy data obtained during the long-term follow-up from 1965 to 1985 of cohorts of Japanese men living in Hawaii and Japan. The search for explanatory variables revealed three with the characteristics of having both opposing patterns of associations with clinical stroke compared with coronary heart disease and of being more prevalent in Japan than in Hawaii. These variables were low serum cholesterol levels, high intake of alcohol, and some aspect of an Oriental diet characterized by low intake of fat and protein from animal sources. Analysis of associations of these variables with measures of atherosclerosis in coronary and cerebral arteries revealed no paradoxical differences, with the possible exception of some dietary variables. Associations with autopsy-measured myocardial infarctions, cerebral infarction, and hemorrhage, however, showed opposing patterns similar to those found for clinical disease. The main inference from this work is that the paradoxically high risk of stroke observed in populations with low risk of coronary heart disease is not due to atherosclerosis in the major cerebral arteries. Rather, it is more likely due to lesions in the small intracerebral arteries and appears to be related to low levels of serum cholesterol, high alcohol intake, and some aspect of a traditional Oriental diet. PMID- 2316493 TI - Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma. AB - Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3). PMID- 2316494 TI - Menstrual and reproductive characteristics and age at natural menopause. AB - Data from women who enrolled between 1935 and 1939 in a long-term prospective study of menstrual and reproductive health, in which menstrual cycles and other events were recorded as they occurred, were analyzed to examine factors associated with age at natural menopause. Analysis was restricted to 561 women who enrolled before age 25 years and recorded data through at least age 44 years. Women with a median cycle length that was less than 26 days at ages 20-35 years reached menopause 1.4 years earlier than those with cycles between 26 and 32 days. The difference in mean menopausal age between women with short cycle length (less than 26 days) and women with long cycle length (33 days or longer) was 2.2 years. Women who had ever been pregnant reached menopause slightly, but statistically significantly, later than women who had never been pregnant. Similarly, women who had ever had a live birth had a slightly later age at menopause compared with nulliparous women. A trend of later age at menopause with increasing parity was also observed. There was no association with age at menarche. Certain of these observations are consistent with proposed mechanisms of cessation of menstrual function. PMID- 2316495 TI - Sensory neuropathy in non-insulin-dependent diabetes mellitus. The San Luis Valley Diabetes Study. AB - A screening neurologic examination capable of detecting distal symmetric (sensory) neuropathy in a large population-based study of non-insulin-dependent diabetes mellitus in San Luis Valley, Colorado, in 1984-1986 is described and validated. The examination, completed in 279 diabetics and 577 controls, had 90% agreement with a standard neurologic examination completed on a subsample of 38 patients. Independent validation of neuropathy status was obtained with the Optacon tactile (vibration) stimulator. Mean, age-adjusted vibration threshold was significantly greater in those with neuropathy than in those without. The subtests of the examination most sensitive in detecting neuropathy were a combination of a positive history of neuropathy symptoms and decreased or absent deep tendon reflexes in both ankles. Age-adjusted prevalence of neuropathy in controls, those with impaired glucose tolerance, and diabetics was 3.9%, 11.2%, and 25.8%, respectively. Prevalence odds ratios were 3.5 and 10.6 for the presence of neuropathy in persons with impaired glucose tolerance and diabetes, respectively, compared with persons with normal glucose tolerance. Neuropathy was significantly associated with age, duration of diabetes, male sex, and glycemic control, but not with Anglo/Hispanic status. PMID- 2316497 TI - Perceptual acuity and the risk of industrial accidents. AB - A case-control study of the risk of injuries incurred by male shipyard workers in Den Helder, The Netherlands, was carried out in 1986-1987. The main focus of interest was factors which can interfere with faculties needed for recognizing warning signals of imminent danger. Three hundred workers who had had at least one injury in the previous 3 1/2 years and 300 matched controls were asked about their current use of alcohol, tranquilizers, and cigarettes; the wearing of spectacles and earplugs; taking a nap at noon; engaging in sports during leisure hours; and involvement in a traffic accident during the past year. The hearing acuity of most of the workers involved in the study, as well as the noise load at work, had been recently assessed. Alcohol consumption, hearing loss greater than 20 dB, and loud noise greater than 82 dB(A) were found to be safety hazards. At this shipyard, the risks attributable to noise and hearing loss together accounted for 43% of the injuries. PMID- 2316496 TI - The validity of estimating the incidence of diabetic retinopathy from prevalence. AB - A method for estimating incidence rates of a disease from prevalence proportions with differential mortality was validated for diabetic retinopathy in a large population of diabetic persons followed for 4 years, 1980-1982 to 1984-1986, in southern Wisconsin. Four-year age- or duration-specific incidence rates of retinopathy were calculated from prevalence and mortality in persons with and those without retinopathy. These rates were lower than the actual rates obtained at the 4-year follow-up examination by 50% or more in most age intervals in both younger and older onset persons. Estimated duration-specific rates were up to 29 and 57% lower than the actual rates in younger and older onset persons, respectively. These discrepancies could not be accounted for by violations of the assumptions underlying the method. In applying the method to diabetic retinopathy, age- and duration-specific incidence may be more appropriate. Such estimated rates agree well with actual rates except in older onset persons with diabetes of short duration. PMID- 2316499 TI - The incidence of viral-associated diarrhea after admission to a pediatric hospital. AB - For determination of the incidence of viral-associated diarrhea after admission to a pediatric hospital, all patients admitted to general pediatrics, cardiology, and neurosurgery wards without diarrhea between January 1 and July 31, 1985 were followed 5 days per week for presence of diarrhea, etiologic agent, and possible risk factors. A total of 1,530 patients were followed for 3,642 days. Of these patients, 69 developed 80 nosocomial diarrhea episodes after 72 hours in hospital for a nosocomial diarrhea rate of 4.5 infected children per 100 admissions. Of 358 patients with an infected roommate, 37 (10.3%) developed nosocomial diarrhea. Etiologic agents recognized included rotavirus (43%), calicivirus (16%), astrovirus (14%), minreovirus (12%), adenovirus (8%), Salmonella sp. (4%), and parvo/picornavirus (3%). The nosocomial diarrhea rate by age was: 0-11 months, 8.8%; 12-35 months, 3.6%; and 36 months or more, 0.6%. The rate by length of stay was: 3-7 days, 8.4%; 8-14 days, 10.4%; 15-21 days, 7.9%; and 22 days or more, 8.8%, and by number of roommates/1,000 patient-days it was: 0-1, 15.7; 2 to 3, 27.7; and 4 or more, 45.2. Patients who acquired diarrhea were more likely to be diapered (9.6% vs. 1.8%, p less than 0.001). Playroom use was not significantly different in the two groups. A total of 64 patients developed diarrhea within 72 hours of admission (community diarrhea rate = 4.2). Nosocomial viral-associated diarrhea is almost exclusively a disease of diapered children less than age 36 months and occurs at any time during hospital stay. It is more common in multibed rooms, but does occur in single-bed rooms. PMID- 2316498 TI - Symptoms, signs, and ill-defined conditions: a leading cause of death among minorities. AB - The Manual of the International Classification of Diseases, Injuries, and Causes of Death includes the category, "symptoms, signs, and ill-defined conditions" for nonspecific causes of death. To determine whether this categorization of cause of death is commonly applied to New Mexico's minority populations, the authors examined state vital records data for 1958-1982. Age-specific and age-adjusted death rates were calculated by 5-year intervals for Hispanics, American Indians, and non-Hispanic whites. Death rates attributed to symptoms, signs, and ill defined conditions in all three major ethnic groups in New Mexico far exceeded the national rate for whites. For males in the period 1978-1982, American Indians had the highest rates (115.6 per 100,000 males), followed by Hispanics (58.3 per 100,000 males), and non-Hispanic whites (49.2 per 100,000 males); the national rates were 41.3 and 13.1 per 100,000 males for blacks and whites, respectively. Comparable differences were observed among females. The authors suggest that the death rate for deaths attributed to symptoms, signs, and ill-defined conditions may be a potential indicator of access to and use of health services and that the categorization may strongly affect cause-specific death rates in minority populations. PMID- 2316500 TI - Epidemic cholera in West Africa: the role of food handling and high-risk foods. AB - During an epidemic of cholera in Guinea, West Africa, in 1986, the authors conducted two studies of risk factors for transmission. In the capital city, 35 hospitalized cholera patients were more likely than 70 neighborhood-matched controls to have eaten leftover peanut sauces (odds ration (OR) = 3.1, 95% confidence interval (CI) 1.2-8.2), but less likely to have eaten tomato sauces (OR = 0.2, 95 percent CI 0.1-0.9). Hand washing with soap before meals by all family members protected against cholera (OR = 0.2, 95 percent CI 0.02-0.96), suggesting that persons asymptomatically infected with Vibrio cholerae 01 may have been the initial source for contamination of the leftover foods. Laboratory studies demonstrated that V. cholerae multiplied rapidly in peanut sauce (pH 6.0), but not in the more acidic tomato sauce (pH 5.0). In an outbreak of cholera like illness after a rural funeral, illness was strongly associated with eating a rice meal served over many hours without reheating. These studies demonstrated that, in this epidemic, many cases of severe cholera were associated with eating specific cooked foods that could support bacterial growth after contamination of these foods with V. cholerae within the household. Epidemic control efforts should include identification of high-risk foods and promotion of simple changes in food handling behaviors to lower the risk of foodborne transmission. PMID- 2316502 TI - Re: "The validity of estimating the incidence of diabetic retinopathy from prevalence". PMID- 2316501 TI - Animal exposures and antibodies to Toxoplasma gondii in a university population. AB - To determine the risk of toxoplasma infection to individuals exposed to cats in a research institution, we compared the prevalence of toxoplasma antibodies with exposure to cats in university employees. Of 116 employees tested, 42 (36 percent) had toxoplasma antibodies as determined by the indirect fluorescent antibody test. Women and individuals aged 35 years or more had a greater prevalence of antibodies. The antibody prevalence by occupation was 72.1 percent for physicians and those with doctorates, 45.3 percent for animal and veterinary technicians, 33.3 percent for research technicians, 28.2 percent for administrative staff, 25.0 percent for graduate students and fellows, and 13.4 percent for veterinarians. There was no significant positive association between exposure to cats and the prevalence of toxoplasma antibodies. A follow-up of seronegative employees, 6 and 18 months later, revealed no seroconversions indicative of acute toxoplasma infection. We concluded that there was no significant risk of toxoplasma infection in university employees exposed to cats. PMID- 2316504 TI - Re: "Ordinal regression models for epidemiologic data". PMID- 2316503 TI - Re: "High incidence and prevalence of rheumatoid arthritis in Pima Indians". PMID- 2316505 TI - Effect of adherent cells on the regulation of BFU-E in patients with myeloproliferative disease. AB - The interaction between adherent cells and red cell progenitors from peripheral blood of patients with polycythemia vera (PV), essential thrombocytosis (ET), and healthy controls was studied. Various combinations of adherent and nonadherent cells were co-cultured in a semisolid system. Adherent cells from controls, when added at low concentrations, stimulated BFU-E proliferation, whereas high concentrations (40% of total cells in the culture) caused a significant decrease in the number of BFU-E colonies in 6/8 PV patients, 4/4 ET patients, and 8/12 controls. On the other hand, low and high concentrations of adherent cells from both patients with PV and ET caused a significant increase in BFU-E from either patients or controls. Moreover, adherent cells from these patients induced endogenous BFU-E proliferation (independent of erythropoietin) in nonadherent cells of 12/12 normal controls. The results show that BFU-E from patients with PV and ET are sensitive to suppression by normal adherent cells. On the other hand, adherent cells from these patients possess stimulatory activity on BFU-E from peripheral blood at all concentrations and are devoid of the inhibitory activity. This suggests a possible defect in the functioning of adherent cells in PV and ET patients which may contribute to the abnormal regulation of hematopoiesis in these disorders. PMID- 2316506 TI - Hematological abnormalities in hemophilic patients with human immunodeficiency virus infection. AB - Hematological abnormalities are common in patients with AIDS or AIDS-related complex. We studied cytological characteristics in peripheral blood and bone marrow samples of 33 hemophilic patients with HIV Infection and in six HIV negatives. The HIV-positive patients presented leukopenia (60.6%), thrombocytopenia (69.9%), and anemia (57.5%). Bone marrow showed abnormalities of maturation in one or more cell lines similar to those described in other HIV infected groups of patients. These findings were more prominent in megakaryocytes and granulocytic series. Lymphocytosis, plasmocytosis, and increased hemophagocytosis were also common. These alterations do not appear in HIV negative patients and seem related to a direct effect of HIV on bone marrow cells or to alterations in T-cell regulatory functions. PMID- 2316507 TI - Effect of histocompatibility factors on pulmonary retention of indium-111-labeled granulocytes. AB - Granulocyte transfusions are associated with a number of side effects including febrile transfusion reactions and occasionally pulmonary infiltrates. There is evidence that the presence of preformed antibodies may be a cause of these complications. In this study, allogeneic 111Indium-labeled granulocytes were used to evaluate the pulmonary retention of radioactivity in alloimmunized and non alloimmunized patients in an attempt to assess antibody effect on granulocyte migration. After injection of labeled allogeneic granulocytes into neutropenic patients, the ratios of lung to heart activity were calculated for the first 30 min of scanning. There was significantly greater retention of radioactivity from cells in the lungs of patients who were alloimmunized, having both lymphocytotoxic (anti-HLA) and leuko-agglutinating antibodies, compared to the activity in the lungs of non-alloimmunized patients (P less than .001) or of patients receiving autologous granulocytes (P less than .001). This study demonstrates that labeled, mismatched granulocytes may be retained in the lungs for a significantly longer time in patients with preformed antibodies. This implies that transfusion of large numbers of such mismatched granulocytes, i.e., granulocyte transfusions, may also be retained in the lungs of alloimmunized patients, which could lead to pulmonary compromise. Therefore, granulocyte transfusions from random donors should not be given to alloimmunized patients. PMID- 2316508 TI - In vivo aging of red cell enzymes: study of biotinylated red blood cells in rabbits. AB - It is generally recognized that the activities of some of the red cell enzymes decline as the cell ages. However, there is still a controversy regarding the rate at which this aging occurs. In the present study we applied newly developed technology for the specific isolation of maturing reticulocytes/erythrocytes for a more comprehensive study of in vivo aging of red cell enzymes in rabbits. Anemia was induced by repeated phlebotomy, and reticulocyte-rich erythrocytes were labeled with N-hydroxy succinimido-biotin and then transfused into a normal rabbit. These biotinylated cells were isolated at various time points by their affinity for an avidin support, and the enzymatic activity of 19 red cell enzymes was measured. We observed a biphasic pattern of decay for the activity of six age dependent enzymes--aldolase, glutamate-oxaloacetate transaminase, glucose 6 phosphate dehydrogenase, hexokinase, pyrimidine 5'-nucleotidase, and pyruvate kinase. PMID- 2316509 TI - Detection of engraftment and chimerism after bone marrow transplantation by in situ hybridization using a Y-chromosome specific probe. AB - After bone marrow transplantation (BMT), the recipient and donor cells must be distinguished from each other to document and characterize successful engraftment. In addition to dot blot and Southern blot analyses, we have performed in situ hybridization in two sex-mismatched cases using a Y-chromosome specific DNA probe (PHY10). In situ hybridization showed that greater than 95% of the peripheral mononuclear cells had clusters of grains indicative of male cell origin in a recipient girl (case 1), and no cells had clusters of grains in another recipient boy (case 2) at the time of engraftment and 3 months after BMT. In situ hybridization using the PHY10 probe appears to facilitate identification of individual cells of male and female origin, and it requires only 20 hr to obtain the results. The technique provides a powerful new method for the documentation of engraftment and the detection of mixed hematopoietic chimerism in peripheral blood and bone marrow cell compartments after BMT. PMID- 2316511 TI - Familial macrothrombocytopenia associated with decreased glycosylation of platelet membrane glycoprotein IV. AB - A case of hereditary thrombocytopenia with large platelets (familial macrothrombocytopenia, FM) is reported. Studies on the platelets from the propositus showed decreased glycosylation of platelet membrane glycoprotein IV, which would distinguish the case from other FM previously described. PMID- 2316510 TI - Enhanced botrocetin-induced type IIB von Willebrand factor binding to platelet glycoprotein Ib initiates hyperagglutination of normal platelets. AB - Botrocetin, a protein isolated from the venom of the snake Bothrops jararaca, induces platelet aggregation/agglutination by von Willebrand factor (vWF) binding to the membrane glycoprotein (GP) Ib, an action resembling that of ristocetin. However, some differences in the interaction between vWF and platelet GPIb induced by these two substances have been reported. We have recently shown that the GPIb binding domain on the vWF molecule, in both instances, resides in the tryptic 52/48 kDa fragment extending from amino acid residue 449 to 728 of the constituent subunit. In the present report, we demonstrate that botrocetin does not induce agglutination of formalin-fixed platelets from a patient with Bernard Soulier syndrome congenitally lacking GPIb and GPIX as well as GPV, a finding similar to that shown with ristocetin. A monoclonal antibody against GPIb (AP-1) inhibits either ristocetin- or botrocetin-dependent vWF binding to formalin-fixed platelets from normal individuals. Therefore, botrocetin-induced vWF binding to formalin-fixed platelets may reflect the interaction between vWF and platelet GPIb. To strengthen this concept, we have now found that heightened botrocetin induced type IIB vWF binding to platelet GPIb causes hyperagglutination of normal platelets. PMID- 2316512 TI - Effects of 2'-deoxycoformycin on HL-60 cell differentiation, adenosine deaminase, and oligoadenylate synthetase. AB - There is evidence that 2'-deoxycoformycin (DCF) functions as a differentiating agent. We examined the effects of DCF on the differentiation of HL-60 cells, a standard model of leukemic cell differentiation. DCF did not induce morphologic or histochemical evidence of differentiation, nor did it interact with retinoic acid, 1,25-dihydroxyvitamin D3, or interferon-gamma in inducing differentiation. Furthermore, DCF and agents that differentiated HL-60 cells had opposing effects on adenosine deaminase and 2',5'-oligoadenylate synthetase activity. PMID- 2316513 TI - Treatment of patients with disseminated intravascular coagulation by protein C. AB - The therapeutic effect of highly purified protein C (PC) or activated protein C (APC) on three patients with disseminated intravascular coagulation (DIC) was tested. In two out of three cases, although therapeutic dose of heparin was not effective, PC or APC administration significantly improved the hypercoagulable state. In one case with acute leukemia who developed DIC with the severe gastrointestinal bleeding, APC corrected the hypercoagulable state without aggravating bleeding. These findings suggested that PC and/or APC might be effective in correcting hypercoagulable state without any adverse effect. PMID- 2316515 TI - MCHC in intravascular hemolysis. PMID- 2316514 TI - Pulmonary embolism and splenic infarction in a patient with sickle cell trait. AB - A 43 year-old black man with sickle cell trait documented by hemoglobin electrophoresis presented with severe pleuritic chest pain and hypoxemia three weeks after discharge following abdominal surgery. A pulmonary embolus was diagnosed by angiography and he was treated with heparin; the minimum arterial pO2 was 55 torr while O2 was being administered at a rate of 3 L/min. During this therapy, he developed abdominal pain. Computerized tomography suggested splenic infarction, which was documented by radionuclide liver-spleen scan and magnetic resonance imaging (MRI); the patient's spleen had been normal at exploratory laparotomy three weeks previously. No source for emboli was identified in the deep venous system by MRI. Although splenic infarction has been reported in patients with sickle cell trait at high altitude, this is the first reported case of splenic infarction secondary to the hypoxemia of pulmonary embolism in a patient with sickle cell trait. The spleen is subject to infarction in sickle cell trait because blood flow is slow through a hypoxemic and acidemic environment. The additional hypoxemia due to pulmonary embolism is presumed, in our patient, to have created a local splenic environment which permitted infarction to occur. PMID- 2316516 TI - Marfan syndrome: light at the end of the tunnel? PMID- 2316517 TI - Do twin Lyons have larger spots? PMID- 2316518 TI - Opinion: how can one study individual variation for 3 billion nucleotides of the human genome? PMID- 2316519 TI - Duplicational mutation at the Duchenne muscular dystrophy locus: its frequency, distribution, origin, and phenotypegenotype correlation. AB - Partial gene deletion is the major cause of mutation leading to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Partial gene duplication has also been recognized in a few cases. We have conducted a survey for duplication in 72 unrelated nondeletion patients, analyzed by Southern blot hybridization with clones representing the entire DMD cDNA. With careful quantitative analysis of hybridization band intensity, 10 cases were found to carry a duplication of part of the gene, a frequency of 14% for nondeletion cases (10/72), or 6% for all cases (10/181). The extent of these duplications has been characterized according to the published exon-containing HindIII fragment map, and in six of the 10 duplications a novel restriction fragment that spanned the duplication junction was detected. The resulting translational reading frame of mRNA has been predicted for nine duplications. A shift of the reading frame was predicted in four of the six DMD cases and in one of the two intermediate cases, while the reading frame remained uninterrupted in both BMD cases. RFLP and quantitative Southern blot analyses revealed a grandpaternal origin of duplication in four families and grandmaternal origin in one family. In all five families, the duplication was found to originate from a single X chromosome. Unequal sister chromatid exchange is proposed to be the mechanism for the formation of these duplications. PMID- 2316520 TI - Mental retardation in heterozygotes for the fragile-X mutation: evidence in favor of an X inactivation-dependent effect. AB - The still debated question of whether the expression of mental retardation in heterozygous carriers of the Martin-Bell syndrome is influenced by X inactivation has been investigated in a group of phase-known double heterozygotes for the FRA X mutant and the G6PD Mediterranean variant. In these individuals, the number of somatic cells (fibroblasts or red cells) with an active FRA-X chromosome could be assessed through the G6PD phenotype at the single-cell level. The data reported indicate a significant inverse correlation between the IQ level (as measured by the Wechsler-Bellevue test) and the percentage of fibroblast cells with an FRA-X active chromosome. In contrast, no significant correlation was found when the IQ level and red cell data were compared, thus suggesting the occurrence of somatic selection against hematopoietic stem cells with an active FRA-X chromosome. PMID- 2316521 TI - Methylation status of genes flanking the fragile site in males with the fragile-X syndrome: a test of the imprinting hypothesis. AB - Laird has suggested that the mutation responsible for the fragile X (FraX) syndrome interferes with the process of X chromosome reactivation in oocytes, thus blocking the transcription of loci at or neighboring the fragile site (Xq27.3) and producing the clinical FraX phenotype; he has also suggested that the transcriptional block might result from inappropriate DNA methylation. We have explored the latter possibility by examining the methylation status of several genes flanking the fragile site in eight FraX males from seven unrelated families. These genes (HPRT, G6PD, P3, and GdX), contain 5' clusters of CpG dinucleotides which are differentially methylated in transcriptionally active and inactive loci. Using the methylation-sensitive restriction enzyme, HpaII, we observed no differences between FraX and normal males in the methylation either of CpG islands in any of these genes or in nonclustered CpGs within the body of the HPRT gene. The same was true for the CpG cluster in intron 22 of the clotting factor VIII gene. In each gene, the island is methylated on the inactive X chromosome and not on the active one, but in no case were these islands methylated in FraX males. The four anonymous loci (DXS98, DXS304, DXS52, and DXS15) that are closely linked to the FraX locus (the closest is within 5 centimorgans) are not differentially methylated on active and inactive X, nor are they unusually methylated in FraX males. Therefore, our observations provide no evidence that DNA methylation in the vicinity of the FraX locus has a role in producing the clinical phenotype of the FraX syndrome. PMID- 2316522 TI - The parental origin of the extra X chromosome in 47,XXX females. AB - We used X-linked DNA polymorphisms to study the parental origin of X chromosome nondisjunction in 28 47,XXX live-born females. Errors in oogenesis accounted for 26 of the cases, with the majority of these being attributable to an error at meiosis I. We observed an association between advanced parental age and meiosis I nondisjunction--but not meiosis II nondisjunction--in the maternally derived cases. In studies of recombination we found little evidence for an association between pairing failure and X chromosome nondisjunction, but our results suggest that increased recombination near the centromere may play a role in the etiology of the 47,XXX condition. PMID- 2316523 TI - Five polymorphic microsatellite VNTRs on the human X chromosome. AB - The human genome contains approximately 50,000 copies of an interspersed repeat with the sequence (dT.dG/dA.dC)n, where n = approximately 10-60. We and others have found that several of these repeats have variable lengths in different individuals, with allelic fragments varying in size by multiples of 2 bp. These "microsatellite" variable number of tandem repeats (VNTRs) may be scored by PCR, using unique flanking primers to amplify the repeat-containing regions and resolving the products on DNA sequencing gels. Since few VNTRs have been found on the X chromosome, we screened a flow-sorted X chromosome-specific genomic library for microsatellites. Approximately 25% of the phage clones hybridized to a poly (dT-dG).poly(dA-dC) probe. Of seven X-linked microsatellites present in positive phages, five are polymorphic and three have both eight or more alleles and heterozygosities exceeding 75%. Using PCR to amplify genomic DNAs from hybrid cell panels, we confirmed the X localization of these VNTRs and regionally mapped four of them. The fifth VNTR was regionally mapped by virtue of its tight linkage to DXS87 in Centre du Polymorphisme Humain families. We conclude that whatever factors limit the occurrence of "classical" VNTRs and RFLPs on the X chromosome do not appear to operate in the case of microsatellite VNTRs. PMID- 2316524 TI - A human alpha satellite DNA subset specific for chromosome 12. AB - We have isolated a DNA clone (pBR12, locus D12Z3) which identifies an alphoid subset specific for chromosome 12. This alphoid subset has an EcoRI periodicity of 680 bp and is characterized by a higher-order repeat of about 1.4 kb (eight basic units of about 170 bp each) as revealed by several restriction enzymes. The sequence analysis confirmed the alphoid nature of pBR12 and the dimeric organization. PMID- 2316525 TI - Genetic mapping of autosomal dominant Charcot-Marie-Tooth disease in a large French-Acadian kindred: identification of new linked markers on chromosome 17. AB - We have performed linkage analysis in a large French-Acadian kindred segregating one form of autosomal dominant Charcot-Marie-Tooth disease (CMTD) (type IA) using 17 polymorphic DNA markers spanning human chromosome 17 and demonstrate linkage to several markers in the pericentromeric region, including DNA probes pA10-41, EW301, S12-30, pTH17.19, c11-2B, and p11-2c11.5. Linkage of markers pA10-41 and EW301 to CMTD type IA has been reported elsewhere. Four new markers, 1516, 1517, 1541, and LL101, which map to chromosome 17 have been identified. The marker 1516 appears to be closely linked to the CMTD locus on chromosome 17 as demonstrated by a maximum lod score of 3.42 at theta (recombination fraction) = 0. This marker has been mapped to 17p11.2 using a somatic cell hybrid constructed from a patient with Smith-Magenis syndrome [46,XY, del(17)(p11.2p11.2)]. A lod score of 6.16 has been obtained by multipoint linkage analysis with 1516 and two markers from 17q11.2, pTH17.19, and c11-2B. The markers 1517 and 1541 have been mapped to 17p12-17q11.2 and demonstrate maximum lod scores of 2.35 and 0.63 at recombination values of .1 and .2, respectively. The marker LL101 has been mapped to 17p13.105-17p13.100 and demonstrates a maximum lod score of 1.56 at a recombination value of .1. Our study confirms the localization of CMTD type IA to the pericentromeric region of chromosome 17. PMID- 2316526 TI - Characterization of the normal alpha 1-antitrypsin allele Vmunich: a variant associated with a unique protein isoelectric focusing pattern. AB - alpha 1-Antitrypsin (alpha 1AT), the major serum inhibitor of neutrophil elastase, is a highly polymorphic protein associated with isoelectric focusing (IEF) patterns typical for each variant. alpha 1AT Vmunich, a previously unreported normal alpha 1AT variant, has a unique IEF banding pattern in which the 7 and 8 alpha 1AT protein bands focus with the normal M-type 7 and 8 bands, despite the fact that the major fraction of the Vmunich protein focuses in the "V" region of the IEF gel. To characterize the molecular basis of this variant and its unique IEF pattern, DNA sequence analysis of the coding exons of the Vmunich alpha 1AT gene was carried out using the polymerase chain reaction. The Vmunich allele differed from the common normal M1(Val213) alpha 1AT allele by a single nucleotide substitution of cytosine for adenosine, with the resultant amino acid change Asp2 GAT----Ala GCT. Inheritance of the allele was confirmed by family analysis using allele-specific amplification with the polymerase chain reaction. The Asp2----Ala mutation explains the cathodal position of the Vmunich protein on IEF, as there is a substitution of a negatively charged amino acid by a neutral one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316527 TI - Intraspecific nucleotide sequence differences in the major noncoding region of human mitochondrial DNA. AB - Nucleotide sequences of the major noncoding region of human mitochondrial DNA (mtDNA) from 95 human placentas have been determined. These sequences include at least a 482-bp-long region encompassing most of the D-loop-forming region. Comparisons of these sequences with those previously determined have revealed remarkable features of nucleotide substitutions and insertion/deletion events. The nucleotide diversity among the sequences is estimated as 1.45%, which is three- to fourfold higher than the corresponding value estimated from restriction enzyme analysis of whole mtDNA genome. A hypervariable region has also been defined. In this 14-bp region, 17 different sequences were detected. More than 97% of the base changes are transitions. A significantly nonrandom distribution of nucleotide substitutions and sequence length variations were also noted. The phylogenetic analysis indicates that diversity among the negroids is much larger than that among the caucasoids or the mongoloids. In fact, part of the negroids first diverged from other humans in the phylogenetic tree. A striking finding in the phylogenetic analysis is that the mongoloids can be separated into two distinct groups. Divergence of part of the mongoloids follows the earliest divergence of part of the negroids. The remainder of the mongoloids subsequently diverged together with the caucasoids. This observation confirmed our earlier study, which clearly demonstrated, by the restriction-enzyme analysis, existence of two distinct groups in the Japanese. PMID- 2316529 TI - AIDS panel finds U.S. public health system lacking, urges national scheme to combat epidemic. PMID- 2316528 TI - Sequence of the E1 alpha subunit of branched-chain alpha-ketoacid dehydrogenase in two patients with thiamine-responsive maple syrup urine disease. AB - Some patients with maple syrup urine disease respond to thiamine administration with a reduction in ketoaciduria and increase in activity of branched-chain alpha ketoacid dehydrogenase. The biochemical mechanism underlying this effect is unknown but may result from decreased affinity of the mutant enzyme for thiamine or from stabilization of the abnormal enzyme by thiamine. The E1 alpha subunit of the complex participates in the thiamine-dependent decarboxylation of branched chain alpha-ketoacids. We sequenced the E1 alpha subunit by using reverse transcription of RNA followed by enzymatic amplification of cDNA in two patients with thiamine-responsive maple syrup urine disease. The deduced amino acid sequence of this subunit in the patients was identical to that in normal controls, suggesting that in the patients the thiamine-binding site is abnormal because of a mutation in the E1 beta subunit. Other possible explanations are (a) that a mutation in the E1 beta or E2 subunits either alters thiamine binding by E1 alpha because of allosteric interactions or causes the complex to be unstable and (b) that thiamine stabilizes the complex. PMID- 2316530 TI - Precipitation of teniposide during infusion. PMID- 2316532 TI - Incompatibility of cefoperazone and promethazine. PMID- 2316531 TI - Changes in recommendations for reconstituting Kefurox injection. PMID- 2316534 TI - Facilitating computer interfaces with the Health Level Seven standard. PMID- 2316533 TI - Cost-effective alternative to aminocaproic acid syrup. PMID- 2316535 TI - Hospital-based immunization: a leadership role for hospital pharmacists. PMID- 2316536 TI - Helping people make the best use of their medications. PMID- 2316537 TI - Doing the right thing for patients. PMID- 2316538 TI - Opportunities and responsibilities in pharmaceutical care. AB - Pharmacy's opportunity to mature as a profession by accepting its social responsibility to reduce preventable drug-related morbidity and mortality is explored. Pharmacy has shed the apothecary role but has not yet been restored to its erst-while importance in medical care. It is not enough to dispense the correct drug or to provide sophisticated pharmaceutical services; nor will it be sufficient to devise new technical functions. Pharmacists and their institutions must stop looking inward and start redirecting their energies to the greater social good. Some 12,000 deaths and 15,000 hospitalizations due to adverse drug reactions (ADRs) were reported to the FDA in 1987, and many went unreported. Drug related morbidity and mortality are often preventable, and pharmaceutical services can reduce the number of ADRs, the length of hospital stays, and the cost of care. Pharmacists must abandon factionalism and adopt patient-centered pharmaceutical care as their philosophy of practice. Changing the focus of practice from products and biological systems to ensuring the best drug therapy and patient safety will raise pharmacy's level of responsibility and require philosophical, organizational, and functional changes. It will be necessary to set new practice standards, establish cooperative relationships with other health care professions, and determine strategies for marketing pharmaceutical care. Pharmacy's reprofessionalization will be completed only when all pharmacists accept their social mandate to ensure the safe and effective drug therapy of the individual patient. PMID- 2316539 TI - Pharmaceutical care: pharmacy's mission for the 1990s. AB - The case for pharmaceutical care as pharmacy's mission for the 1990s is presented. The emergence of pharmacy as a clinical profession has given pharmacists the skills and knowledge to improve the outcomes of drug therapy. It also presents them with the responsibility for those results. Practitioners of pharmaceutical care are concerned with the effect of their services on patients' quality of life and not merely with the act of providing services. They work with other health-care professionals as equals to ensure that therapeutic goals are achieved and that drug-related illness does not occur or is quickly detected and resolved. To be accepted and implemented, pharmaceutical care must first overcome pharmacy's product- and service-oriented focus, opposition from other health-care professions and drug manufacturers, financial and logistical problems, and ignorance and inertia among pharmacists themselves. Through a united effort, pharmacy organizations, schools, and individual pharmacists can translate the need for pharmaceutical care into demands for it by patients, insurance companies, health maintenance organizations, and the government. Pharmaceutical skills and knowledge have developed to the point where pharmacists must share in responsibility for the outcomes of drug therapy. PMID- 2316540 TI - Integrated patient-specific model of pharmacy practice. AB - The deficiencies of traditional models for the provision of clinical pharmacy services are discussed, and a patient-specific model that integrates drug distribution and clinical pharmacy functions is proposed. Traditional models have either designated specific individuals as providers of clinical pharmacy services or have combined distributive and supportive services with clinical services. In both cases, clinical services have been of secondary importance. Such models have resulted in inconsistent clinical services for which the patient is not necessarily the primary focus and have made it difficult for pharmacists to understand their mission. The lack of a well-defined primary clinical role for pharmacists has confused health-care providers and created problems for managers attempting to evaluate pharmacists and justify clinical services. The integrated patient-specific model is based on the ethical imperative that the patient must be central to any health-care endeavor. Under this model, clinical pharmacy services are of central importance and distributive services are integrated as a secondary but still very important aspect of comprehensive institutional pharmacy services. Critical elements of the integrated model include a patient-centered philosophy of practice, a definition of clinical pharmacy work, and a managerial framework. The integrated patient-specific model of pharmacy practice puts pharmacists in a professional relationship with patients and explicitly defines clinical services and priorities. PMID- 2316541 TI - Time and cost requirements for decentralized pharmacist activities. AB - Time and cost requirements for pharmaceutical services in patient-care areas at a 548-bed university hospital were studied. The study was conducted in 1987 and 1988 to (1) define the clinical and distributive activities of decentralized pharmacists, (2) develop time standards for each activity, (3) determine whether the time requirements of decentralized pharmacists depend on the type of patient involved, (4) determine the actual costs of decentralized pharmacist services for various types of patient, and (5) compare costs with reimbursement for clinical pharmacy services. Time standards were established based on data from seven patient categories representing a cross section of the institution's patients. The mean frequency of each activity and the total time and cost per patient day for all activities were determined. Pharmacist time spent daily in each patient service category ranged from 2.3 hr for low-intensity medical care to 20.8 hr for trauma-burn intensive care. Decentralized pharmacists spent approximately 50% of their time on clinical activities in all patient-service categories. The daily cost per patient day for clinical activities was lowest for low-intensity medical care and highest for adult intensive care. The institution's daily charge for clinical activities ($10/admission and $10/day) exceeded the cost of clinical services during the study period. The decentralized pharmacist time requirement per patient day, and thus the costs of delivering pharmaceutical services, varied by patient-service category. The provision of clinical services generated a profit. A pharmacy workload analysis system that can identify costs and correlate them with patient types can be valuable in hospital pharmacy management. PMID- 2316542 TI - Restructuring pharmacy services to reduce expenses without eliminating services. AB - The manner in which pharmaceutical services in a 719-bed teaching institution were restructured to reduce expenses without eliminating services is described. Before the department was restructured, the labor-intensive nature of the drug distribution system and high personnel costs hindered the introduction of upgraded services. Drugs were dispensed from a central pharmacy and 14 pharmacy satellites located throughout the hospital campus. A traditional floor stock system was used in the critical-care units, the operating suites, and the pediatric facility; i.v. admixture services were provided to only two patient care units. Under a three-year strategic plan, the organizational structure of the department was changed to regroup existing functions and to give more autonomy to the managers. The 12 small pharmacy satellites in the main hospital building were replaced by two larger and more efficiently designed satellites. An automated medication order entry system with bar-code-reading capabilities was installed; automation was also used to increase the efficiency of the nutritional support and oncology services and to create an online file of all statistical, fiscal, and purchasing records. Fax machines that were installed on five critical care units and the oncology unit decreased turnaround time for new medication orders. These changes enabled the department to eliminate 17 positions while adding 5 clinical pharmacist specialist positions and 6 technician group leader positions. By integrating automation technology with controlled downsizing and restructuring of drug distribution services, the department was able to reduce expenses while improving existing pharmaceutical services. PMID- 2316543 TI - Integration of clinical and administrative strategies to reduce expenditures for antimicrobial agents. AB - A comprehensive program of clinical and administrative strategies to reduce expenditures for antimicrobial agents is described. Clinical intervention strategies include the use of antimicrobial order sheets, standardized dosage regimens, restriction policies for certain antimicrobial agents, and position statements on the use of restricted agents. A cornerstone of the program is the support for cost-reduction interventions offered by the pharmacy and therapeutics committee and its subcommittee on therapeutics; that support is demonstrated through endorsement and enforcement of pharmacy programs. Physicians are reminded of the cost-reduction programs through periodic articles in the pharmacy newsletter and an "antibiogram" card supplied by the division of epidemiology. The effectiveness of these interventions has been demonstrated by progressive decreases in expenditures for antimicrobial agents during 1987 and 1988. Antimicrobial agents also account for increasingly smaller percentages of the total drug budget. This combination of clinical and administrative strategies reduced expenditures for antimicrobial agents by more than $700,000 over two years without the use of clinical specialists or any apparent sacrifice in the quality of patient care. PMID- 2316544 TI - Implementing and maintaining a private pharmacokinetics practice. AB - The development and maintenance of a private-practice pharmacokinetics service is described. A contracted pharmacokinetics service has been in place at Georgia Baptist Medical Center, a 525-bed hospital, for the past eight years. Physician support, inhouse study results, and literature documentation of the benefits of scheduling drug concentration determinations were used to convince hospital administrators of the value of a pharmacokinetics service. Services were reimbursed by increasing the fee charged for each drug concentration determination, with payment made to the pharmacokinetics service on a monthly basis. The service is associated with the pathology department for administrative purposes. Each member of the pharmacokinetics service is credentialed by the medical staff. The group trains part-time personnel to provide services when needed. Services provided by the group but not required by the contract include collecting quality assurance data, conducting research, serving on hospital committees, writing newsletter articles, conducting inservice-education programs, and providing clinical interventions for nonconsultation patients. This private practice pharmacokinetics service provides high-quality services and is well accepted within the institution. PMID- 2316545 TI - Use of "The Invisible Ingredient" videotape as a public relations tool. PMID- 2316547 TI - ASHP supplemental standard and learning objectives for residency training in critical-care pharmacy practice. American Society of Hospital Pharmacists. PMID- 2316546 TI - Liquefaction times of fatty-type suppositories with and without progesterone. PMID- 2316548 TI - Should the dosage of zidovudine be adjusted in HIV-infected patients with impaired renal function? PMID- 2316549 TI - What is the status of AIDS antibody home test kits? PMID- 2316550 TI - Making a difference: managing hypertension in special patient populations. Proceedings of a symposium. June 7, 1989, New York. PMID- 2316551 TI - Making a difference. Managing hypertension in minority patients. PMID- 2316552 TI - Hypertension in minority populations. Access to care. AB - Data from multiple sources confirm the greater risk of morbidity and mortality from cardiovascular disease that is seen in some minority segments of the population of the United States, when those segments are compared with the population as a whole. In most studies, blacks are shown to have the highest overall mortality rate from cardiovascular disease--higher than the rate for Hispanics, and substantially higher than the rate for whites and Asians. In some of these studies, blacks also have higher rates of both hypertension-related stroke and coronary artery disease. In some of the major clinical trials, Hispanic patients have the next-highest death rate from high blood pressure and ischemic heart disease. In other, smaller studies, however, non-Hispanic whites have had comparable or higher age-adjusted death rates. Asians, by contrast, have significantly lower death rates from cardiovascular disease, irrespective of national origin, and they also have correspondingly lower mortality from stroke and other hypertension-related diseases. As in coronary artery disease, issues related to access to care may be implicated in the disproportionate morbidity and mortality rates noted in black and Hispanic patients, as well as among some lower class segments of the non-Hispanic white population. Access to care may depend upon a number of factors, among them cultural isolation, public awareness, individual and group attitudes, perception of resource availability, actual resources, socioeconomic status, educational level, and peer behavior. PMID- 2316553 TI - Aztreonam's role in the treatment of gram-negative infections. Proceedings of a symposium. March 15, 1989, New York, New York. PMID- 2316554 TI - Immunogenicity and cross-allergenicity of aztreonam. AB - Beta-lactams are responsible for more than half of the allergic drug reactions encountered in the hospital setting. Although most such reactions are mild, the potential for acute and life-threatening reactions cannot be underestimated when considering readministration of beta-lactam agents, such as the penicillins or cephalosporins, to persons who have previously exhibited sensitivity. In addition to concerns about possible allergic reactions to the beta-lactam antibiotics individually, considerable cross-reactivity has been demonstrated among such classes as the penicillins, the cephalosporins, and the imipenems, although it cannot yet be predicted on an individual basis. Early studies of the unique monocyclic beta-lactam--or monobactam--aztreonam, indicated that the new class demonstrated negligible cross-reactivity with the standard beta-lactams both experimentally and clinically.Further, aztreonam was associated with an extremely low (2 percent) incidence of immunologic drug reactions. Aztreonam also has been found to be well-tolerated by highly penicillin-allergic patients. Although further clinical study is indicated, data so far are encouraging. If it is confirmed that monobactams such as aztreonam are minimally cross-reactive, well tolerated by subjects allergic to other beta-lactam antibiotics, and only weakly immunogenic, fewer allergic reactions may be associated with antimicrobial therapy in the future than have been seen with the other available beta-lactam antibiotic drugs. PMID- 2316555 TI - Empiric antibiotic use--aztreonam as a model. AB - Empiric antibiotic therapy, which accounts for over 90 percent of in-hospital therapeutic antibiotic decisions, may be defined as tentative therapy designed to decrease morbidity and mortality associated with severe infection due to unidentified bacterial pathogens. In the 48- to 72-hour interim between presentation and the availability of reliable culture and sensitivity data that allow for definitive therapy, empiric therapy is extremely important. Aztreonam, the first member of the monobactam class of monocyclic beta-lactam antibiotics, is highly active against most gram-negative aerobic bacteria, including Pseudomonas aeruginosa. Its spectrum of activity is similar to that of the aminoglycosides but without the toxicity associated with those agents. For this reason, aztreonam may play an important role in empiric therapy. Currently, it can be recommended as single-agent empiric therapy only for severe urinary tract infections, but in combination with a variety of other agents, it has proved useful against a wide range of bacterial infections, and in certain subgroups, such as penicillin-allergic patients, it may represent the treatment of choice. It is not yet clear whether aztreonam is superior to other relatively nontoxic agents, such as the third-generation cephalosporins or carbapenems, but there is little doubt that this new agent is a generally safe and effective drug for the treatment of suspected gram-negative sepsis. PMID- 2316556 TI - Infections in frail and vulnerable elderly patients. AB - Frail and vulnerable elderly patients, recognized primarily by the presence of such disabilities as immobility, incontinence, and dementia, are at particularly high risk for the development of infectious diseases, which are the leading cause of hospitalization in this population. The infectious diseases most often observed in the debilitated elderly are pneumonias, urinary tract infections, skin infections, and gastroenteritis, with fever a common manifestation. Some of the factors identified as contributing to their increased susceptibility include diminishing physiologic functioning; compromised host-defense mechanisms; increased incidence of mechanical risk factors, such as pressure ulcers, indwelling or condom catheters, feeding tubes, and soft tissue injuries; and comorbidities such as soft tissue or pulmonary edema. In addition to the common infecting pathogens found in the general population, these unique compromising factors increase the risk of elderly patients for aerobic gram-negative bacillary infection. Further increasing the therapeutic dilemma are ethical considerations involved in prolonging treatment that might be considered medical intervention beyond what is routine and necessary. Although the decision to treat must be made on an individual basis, studies have not always shown treatment to provide benefits in terms of quality of life. Once it is decided to treat, however, appropriate therapy is crucial. One of the most important considerations is renal function, which impacts on effectiveness, toxicity, and cost of therapy and is likely to be diminished in elderly patients. A non-nephrotoxic agent, such as aztreonam, may be a more appropriate therapeutic choice than an aminoglycoside antibiotic in this patient population. PMID- 2316557 TI - Gram-negative bacillary pneumonia in the nosocomial setting. Role of aztreonam therapy. AB - Gram-negative bacterial pneumonia is the leading cause of fatal nosocomial infection in this country. Predisposing factors include altered upper respiratory tract flora and altered barriers that normally protect the sterile lower respiratory tract from invasion by pharyngeal bacteria. Aztreonam, which is highly active against most gram-negative pathogens and which does not cause nephrotoxicity, has been evaluated in the treatment of nosocomial pneumonia. In vitro and pharmacokinetic data on aztreonam indicate that this agent provides an alternative agent for use when resistance to cephalosporin and aminoglycoside antibiotics has developed. Data further suggest that aztreonam may interact synergistically with aminoglycosides against gram-negative pathogens. Clinical study supports the usefulness of aztreonam against gram-negative nosocomial pneumonia. Since aztreonam is inactive against gram-positive and anaerobic bacteria, it must be used in combination with other antibiotics when these pathogens are suspected. PMID- 2316558 TI - In vitro effects of cyclosporine on glomerular function. AB - Cyclosporine A (CsA) causes vasoconstriction and decrease in glomerular filtration rate. Experiments were conducted in isolated glomeruli to study effects of CsA of glomerular perfusion and independent of systemic or renal factors. CsA caused a dose dependent decrease in glomerular volume consistent with mesangial contraction. The ultrafiltration coefficient Kf was significantly lower after incubation in 4 X 10(-4) M CsA when compared to control (2.81 +/- 0.2 vs 5.19 +/- 0.5 nl/min X mm Hg; p less than 0.001). Hydraulic conductivity Lp was diminished by CsA from 2.69 +/- 0.11 to 1.41 +/- 0.05 microliter/min X mm Hg X cm2 (p less than 0.001). These findings demonstrate a direct effect of CsA on the glomerulus which must be considered in addition to drug-induced changes in perfusion and tubular function. PMID- 2316559 TI - The use of low dose methotrexate in refractory sarcoidosis. AB - Symptomatic sarcoidosis is usually treated with glucocorticoids; however, glucocorticoids are associated with significant morbidity. Because low dose methotrexate has been successful in treating other inflammatory diseases, methotrexate was used in patients with persistent, symptomatic sarcoidosis. Fifteen patients with either progressive advancing disease or severe side effects with prednisone were treated with methotrexate for at least 6 months. In 13 of 14 evaluable cases there was symptomatic improvement. In 12 of 14 patients there was significant improvement in objective parameters, including a greater than 15% increase in the vital capacity (5 patients), improvement in chest roentgenogram (6 patients), or a greater than 50% reduction in skin lesions (4 patients) or liver function tests (2 patients). In five patients the disease relapsed as methotrexate was being withdrawn; all patients responded to reinstitution of the drug. PMID- 2316560 TI - The effect of HIV infection on phagocytosis and killing of Staphylococcus aureus by human pulmonary alveolar macrophages. AB - Pulmonary alveolar macrophages (PAM) play a central role in host defense against pulmonary infection. The authors studied the number, viability, and ultrastructure of PAM recovered by bronchoalveolar lavage from normal and HIV infected subjects, and their ability to phagocytose and kill Staphylococcus aureus. PAM from HIV-infected subjects who did not have pneumonia were present in greater numbers and phagocytosed significantly more opsonized Staphylococcus aureus (32.5% and 27.3% for nonsmokers and smokers, respectively) than did PAM from healthy controls (19.5% and 18.2%). In 15 patients with AIDS and pneumonia (due to Pneumocystis carinii in 13/15), viability of PAM and their phagocytic capacity were significantly reduced; in smokers with AIDS and pneumonia, the PAM yield was also dramatically decreased. Killing of S. aureus was similar by PAM from all patient groups. HIV infection was associated with the electron microscopic finding in PAM of extensively ruffled PAM cell-surfaces and ingestion of lymphocytes. Thus, HIV infection stimulates the phagocytic capacity and produces morphologic changes consistent with the possibility that PAM are activated by this retroviral infection. In patients with AIDS who develop pneumonia, especially in smokers, the number, viability and phagocytic capacity of PAM are significantly decreased; our study could not determine whether this diminished activity reflects evolution of the HIV infection or a secondary effect of the pneumonia. PMID- 2316561 TI - Clinical assessment of central venous pressure in the critically ill. AB - To evaluate the accuracy of central venous pressure (CVP) assessment in critically ill patients, and measure disagreement amongst clinicians, 50 consecutive intensive care unit (ICU) patients with right internal jugular catheters were examined. CVP was measured by the indwelling catheter, and was assessed by: (1) one of three ICU staff physicians, (2) one of six medical residents, and (3) one of six medical students. There was no significant difference in CVP assessment between medical students, residents, and staff physicians. Although all clinicians tended to underestimate CVP, only the residents did so significantly (p less than 0.05). Sensitivity and specificity, and agreement and correlation between the clinicians' assessment and catheter measurements were higher when ventilated patients were excluded. All clinicians agreed more often and were better at identifying low CVP. In summary, considerable disagreement and inaccuracy exists in the clinical assessment of central venous pressure in critically ill patients. PMID- 2316562 TI - The case for routine umbilical blood acid-base studies at delivery. AB - One of the major goals of obstetricians is to prevent fetal asphyxia. Unfortunately, the commonly used clinical indicators (fetal heart rate monitoring, meconium staining of the amniotic fluid, and Apgar scores) do not have acceptable accuracy in establishing the presence of fetal asphyxia. These subjective assessments often overdiagnose fetal asphyxia and on occasion may fail to detect its presence. The only scientific, objective means of diagnosing fetal asphyxia at delivery is through umbilical blood acid-base studies. This test is convenient, noninvasive, and accurate. The routine use of umbilical blood acid base studies is a major asset to the obstetric team in determining (1) the presence of asphyxia and its consequences, (2) the efficacy of interventions to prevent fetal asphyxia, and (3) the mechanisms responsible for fetal acidosis. PMID- 2316563 TI - Pseudogene/functional gene ratio in late-onset 21-hydroxylase-deficient adrenal hyperplasia. AB - Late-onset adrenal hyperplasia caused by 21-hydroxylase deficiency leads to hyperandrogenic symptoms in 1% to 6% of hyperandrogenic women. Normally there are two 21-hydroxylase genes present in a 1:1 ratio. Gene CYP21A is a nonfunctional pseudogene, whereas CYP21B is an active gene. Abnormalities of the CYP21A/CYP21B gene ratio may serve as a marker for late-onset adrenal hyperplasia. Eight hyperandrogenic patients with late-onset adrenal hyperplasia and five control subjects were studied by evaluation of autoradiograms of Taq I and Kpn I digests by means of laser densitometry. Seven of eight (87%) patients with late-onset adrenal hyperplasia had an abnormal CYP21A/CYP21B gene ratio on laser densitometry, suggestive of CYP21A gene duplication, CYP21B gene deletion, or the conversion of a CYP21B gene to a CYP21A gene. One of the five control subjects had a heterozygous deletion of the CYP21A gene. The CYP21A/CYP21B gene ratio may serve as a useful genetic marker for late-onset adrenal hyperplasia in a non-high risk population. PMID- 2316564 TI - Cigarette smoking as a risk factor for pelvic inflammatory disease. AB - To examine the relationship between cigarette smoking and pelvic inflammatory disease we analyzed data from a hospital-based, case-control study of pelvic inflammatory disease. Case subjects were 197 women hospitalized with their first episode of pelvic inflammatory disease; control subjects were 667 women hospitalized with nongynecologic conditions. Logistic regression was used to control for potentially confounding factors, including number of recent sexual partners, frequency of intercourse, and previous episodes of gonorrhea. Compared with women who had never smoked, current cigarette smokers had a significantly elevated relative risk of pelvic inflammatory disease of 1.7 (95% confidence interval, 1.1 to 2.5). Similarly, former cigarette smokers had a significantly elevated relative risk of pelvic inflammatory disease of 2.3 (95% confidence interval, 1.3 to 4.2). However, a dose-response relationship was not observed. These results suggest that cigarette smoking is associated with pelvic inflammatory disease. Whether or not this association is causal requires clarification. The high prevalence of cigarette smoking and the serious consequences of pelvic inflammatory disease make such clarification an important consideration for future research. PMID- 2316566 TI - Birth weight discordancy in male-first and female-first pairs of unlike-sexed twins. AB - We studied 153 consecutive twin pairs of unlike sex. Comparison of 71 male-female pairs with 82 female-male pairs showed similar mean twin birth weight and rate of discordance. However, males were significantly heavier (p less than 0.04) compared with females in the male-first but not in the female-first combination. The rate of female discordance was significantly higher compared with male discordance in both fetal sex combinations. It is concluded that females of unlike-sexed pairs are at greater risk to be growth discordant. Fetal sex, therefore, should be included as one of several factors that produce divergent twin growth. PMID- 2316567 TI - Pregnancy outcome and fetomaternal hemorrhage after noncatastrophic trauma. AB - Two hundred five consecutive cases of noncatastrophic trauma occurring during the second half of pregnancy were evaluated prospectively. Pregnancy complications as a result of trauma occurred in 18 of 205 patients (8.8%): premature labor (n = 10), placental separation (n = 5), fetal injury (n = 1), and fetal death (n = 2). Multiple regression analysis of the data base showed obstetric findings (contractions, uterine tenderness, and bleeding) on presentation to be highly associated with complications (17/88; 19.3%). In their absence complications were rare (1/117; 0.9%). Detectable fetomaternal hemorrhage was significantly more common in trauma patients (18/205) than in control subjects (2/110) (p less than 0.01), but its role in managing trauma patients was limited to detection of rare massive hemorrhage (1/205) and detection of rare hemorrhage exceeding that covered by the standard Rho (D) immune globulin dose (2/205). Fetomaternal hemorrhage need not be quantitated in patients who lack obstetric findings on presentation. Despite rare reports of delayed abruptio placentae, it is doubtful that prolonged observation (greater than 2 to 3 hours) in the hospital is necessary in patients who lack obstetric findings on initial presentation. PMID- 2316565 TI - Genetic screening with exfoliated cervicovaginal cells collected by a noninvasive lavage technique performed during routine gynecologic cancer screening. AB - We have investigated and established the feasibility of the use of exfoliated cervicovaginal cells as an abundant source of genetic material. We routinely use this material for the detection by molecular hybridization of human papillomavirus infection of the cervix. We have analyzed deoxyribonucleic acid isolated from cervicovaginal cells by Southern blot hybridization to detect a common restriction fragment length polymorphism on chromosome 13. We suggest that in the near future most, if not all, major human genetic disease loci will be cloned and their mutations will be identified. With this knowledge and innovative methods, such as the polymerase chain reaction, it will be possible to distinguish normal individuals who harbor a variety of recessive genetic mutations that may place them at risk to produce offspring with serious genetic diseases. We propose that both genetic and cancer screening can be performed during the same office visit. Such testing offers the advantage of identification of women at risk for genetic disease with a noninvasive procedure before or concurrent with childbearing. Easily accessible genetic material extracted from exfoliated cervicovaginal cells can also be used for population genetic studies. PMID- 2316569 TI - Could antiprogesterones be used as alternative cervical ripening agents? AB - We measured the effect of a progesterone antagonist on the pregnant cervix with a custom-built cervicometer. The change in cervical diameter was studied in 11 pregnant patients after oral administration of 600 mg of RU-486. In all cases RU 486 ripened the cervix (p = 0.0007). The average increase in diameter was 13% (95% confidence limits, 10% to 16%). PMID- 2316568 TI - Mechanisms of parturition: the transfer of prostaglandin E2 and 5 hydroxyeicosatetraenoic acid across fetal membranes. AB - Prostaglandin E2 production by amnion is thought to be an important event in the onset of human labor. It has been suggested that 5-hydroxyeicosatetraenoic acid, also produced in the amnion, may mediate prelabor contractions. For either of these compounds to play a paracrine role they need to cross the chorion, which has a high capacity to metabolize prostaglandins. With the use of an in vitro system we have shown that both prostaglandin E2 and 5-hydroxyeicosatetraenoic acid cross either amnion or intact amnion-chorion-decidua at a rate similar to that of an extracellular marker sucrose. Analysis by high performance liquid chromatography revealed that at physiologic concentrations neither prostaglandin E2 nor 5-hydroxyeicosatetraenoic acid were metabolized by amnion alone. Moreover, 100% of the 5-hydroxyeicosatetraenoic acid and 72% of the prostaglandin E2 remained in the active form after passage across intact amnion-chorion-decidua. There did not appear to be any difference in the rate of transfer or permeability of the membranes before or after spontaneous labor. We conclude that both 5 hydroxyeicosatetraenoic acid and prostaglandin E2 synthesised in the amnion can cross the membranes by diffusion through the extracellular space, remaining largely unmetabolized, and may play a role in the onset of human labor. PMID- 2316570 TI - Myometrial activity after local application of prostaglandin E2 for cervical ripening and term labor induction. AB - Twelve pregnant women at term with unfavorable cervices (less than or equal to 5 points according to Bishop score) were given prostaglandin E2 for cervical priming and labor induction. Prostaglandin E2 was given in the following manner: 0.5 mg in gel strictly intracervically (n = 4), extraamniotically (n = 4), or prostaglandin E2 (4 mg) in gel vaginally (n = 4). The myometrial activity was registered over a period of 30 minutes before and at least 3 hours after gel application by means of an extraamniotic microtransducer catheter. After both extraamniotic and vaginal gel application, myometrial activity was significantly increased compared with intracervical application. All the women had favorable cervical states 6 hours after treatment and were delivered vaginally within 24 hours. All infants were delivered in good condition with 1-minute Apgar scores greater than 7. From these results we conclude that proper intracervical prostaglandin E2 gel application, in contrast to extraamniotic or vaginal application, induces cervical ripening without significant myometrial activity. Because careful intracervical application appears to avoid or minimize the risks of myometrial hyperstimulation, this technique should be considered particularly in women with unfavorable cervices and delicate fetuses. PMID- 2316571 TI - Management of severe postpartum hemorrhage by intrauterine irrigation with prostaglandin E2. AB - Continuous intrauterine irrigation with minute amounts of prostaglandin E2 was used in 22 patients with severe postpartum hemorrhage unmanageable by conventional therapy. Twenty-one women were treated because of uterine atonic hemorrhage and one because of late postpartum hemorrhage from subinvolution. A quick tetanic contraction of the uterine muscle with dramatic and sustained hemostasis was achieved in all patients. The therapeutic response was continuous and uninterrupted regardless of the predisposing factors for the hemorrhage or the hemodynamic condition of the patients. No side effects were observed. PMID- 2316572 TI - Postpartum pulmonary embolus as an unusual cause of cortical blindness. AB - A pregnant patient was delivered by cesarean section with blindness occurring in the postoperative period. Diagnostic evaluation revealed the presence of massive pulmonary embolus associated with cardiogenic shock. The differential diagnosis of blindness during pregnancy is discussed. PMID- 2316573 TI - Antepartum heart rate patterns in small-for-gestational-age third-trimester fetuses: correlations with blood gas values obtained at cordocentesis. AB - Antepartum fetal heart rate records were made immediately before cordocentesis and blood gas analysis in 58 small- and 29 appropriate-for-gestational-age fetuses at 27 to 38 weeks' gestation. All appropriate-for-gestational-age fetuses had blood PO2 and pH values within the normal ranges for gestation, and in 27 of 29 cases the heart rate pattern was reactive; in two it was nonreactive. Abnormal heart rate patterns were present in 15 of the 19 small-for-gestational-age fetuses that were found to be hypoxemic, acidemic, or both. The abnormalities included decreased baseline variation, absence of accelerations, presence of decelerations, and increased baseline heart rate. A repetitive decelerative pattern best identified the hypoxemic fetuses. Fetal PO2 values in the lower normal range, present in many of the small-for-gestational-age fetuses, were in general associated with a reactive fetal heart rate pattern. PMID- 2316574 TI - Fetal assessment based on fetal biophysical profile scoring. IV. An analysis of perinatal morbidity and mortality. AB - The relationship between the last biophysical profile score result and perinatal outcome was determined among a large referred population of high-risk pregnancies. A highly significant inverse linear correlation was observed for fetal distress, admission to neonatal intensive care unit, intrauterine growth retardation, 5-minute Apgar score less than 7, and umbilical cord pH less than 7.20 but not for the incidence of meconium or major anomaly. A highly significant inverse exponential (log 10) relationship was observed for perinatal mortality in total and by component parts and cause. These data strongly suggest the biophysical profile scoring method of fetal risk assessment is accurate and also provides insight into the extent of fetal compromise. PMID- 2316575 TI - Blood exposure in single versus double gloving during pelvic surgery. AB - In light of continued reports suggesting the inadequacy of surgical gloves as sterile barriers, as well as an increasing number of reports describing intraoperative cross infections, a prospective study was performed comparing the presence of visible blood on the hands of surgeons wearing single or double gloves during 45 consecutive major obstetric and gynecologic operations. Single gloved hands revealed the presence of visible blood in 38% of cases (n = 42) whereas visible blood was noted in only 2% of double-gloved hands (n = 48) (p less than 0.001). These results demonstrate that the sterile barrier between surgeon and patient was compromised intraoperatively and that particles the size of red blood cells were able to cross this barrier. In addition, these data suggest single gloving may be less than optimal in maintaining a sterile barrier, as well as strongly suggesting that double gloving can improve the integrity of the patient-surgeon sterile barrier during pelvic surgery. PMID- 2316576 TI - Single-dose antibiotic prophylaxis for patients undergoing extended pelvic surgery for gynecologic malignancy. AB - The comparative efficacy of single-dose antibiotic prophylaxis was retrospectively evaluated in 116 patients undergoing extended pelvic surgical procedures with curative intent. During the 24-month period, other important variables such as surgeon's experience, duration of preoperative hospitalization, preoperative preparation, method of hair removal, suture type, suture size, use of drains, use of cautery, and abdominal closure were controlled. The overall surgical site infection rate was 4.3% after radical hysterectomy with lymphadenectomy and 4.5% after total hysterectomy with lymphadenectomy. In this clinical situation the use of a single dose of antibiotic prophylaxis theoretically decreases cost and patient exposure and appears to be as efficacious as a multiple-dose regimen. PMID- 2316577 TI - The mons pubis: an excellent graft donor site in gynecologic surgery. AB - Split-thickness skin grafting has many applications in gynecologic surgery. Selection of the donor site is an aspect of the procedure that is very important for preventing highly visible lifelong scars. In this regard the mons pubis is an excellent choice as a donor site. Scar visibility is minimized by regrowth of the pubic hair. Another advantage is the anterior location of the mons, which allows for healing without constant pressure in patients who must remain supine in the postoperative period. Graft harvesting requires shaving the mons pubis and injecting saline solution into the subcutaneous tissue to elevate the skin and thus provide a firm flat base for dermatome application. Hair growth does not occur in the recipient site because the hair follicles are not harvested. Healing of both donor and recipient sites has been excellent with minimal discomfort during pubic hair regrowth. Thus it is recommended that the mons pubis be given serious consideration as a graft donor site in gynecologic surgery. PMID- 2316578 TI - Ectopic pregnancy concurrent with induced abortion: incidence and mortality. AB - From 1972 through 1985, 24 women who underwent an induced abortion died as a result of a concurrent ectopic pregnancy. We analyzed data from the Joint Program for the Study of Abortion, National Hospital Discharge Survey, and the Centers for Disease Control Ectopic Pregnancy and Abortion Surveillance Systems to determine the incidence and mortality of ectopic pregnancy concurrent with induced abortion. During the period 1971 through 1985, the incidence of ectopic pregnancy concurrent with induced abortions was 1.35/1000 induced abortions, compared with 13.6/1000 pregnancies not terminated by induced or spontaneous abortion. The rate was higher among women who obtained abortions at earlier gestational age and among older women. The death-to-case rate for ectopic pregnancies concurrent with induced abortion was 1.3 times higher than that for women not undergoing abortion. Most of the deaths of women with ectopic pregnancy who underwent induced abortion were attributable to the failure to diagnose the ectopic pregnancy before the woman left the facility where the abortion was performed. Such deaths could be prevented by the provider of the abortion assuring that the tissue is examined for products of conception at the time of the abortion. PMID- 2316579 TI - Thrombocytopenia at delivery: a prospective survey of 6715 deliveries. AB - Thrombocytopenia occurred in 513 (7.6%) of 6715 consecutive deliveries that occurred in our hospital over a 3-year interval. The patients with thrombocytopenia could be divided into three groups. The largest group (65.1%) consisted of healthy women whose thrombocytopenia was incidentally detected. The next group of patients (13.1%) was composed of healthy women who had an obstetric or medical condition such as diabetes or premature labor. No mother or infant in either group had excessive bleeding, and no infant had a cord platelet count less than 50 x 10(9) per liter. The last group (21%) was composed of hypertensive patients and patients with immune thrombocytopenia. Two infants in this group had cord platelet counts less than 50 x 10(9) per liter, but neither had bleeding. This study indicates that incidental thrombocytopenia in an otherwise well woman at term is the most frequent type of thrombocytopenia and poses no apparent risk for mother or infant at delivery. PMID- 2316580 TI - The neuropeptide histidyl proline diketopiperazine throughout human pregnancy: an inverse correlation with amniotic fluid prolactin. AB - Histidyl proline diketopiperazine values have been established in human amniotic fluid (n = 81) and maternal serum (n = 36) throughout gestation (10 to 42 weeks). Newborn cord serum (n = 10) and first-voided fetal urine (n = 10) levels were also documented. These measurements reveal increasing amniotic fluid levels with term gestation values (15,551 pg/ml) nearly thirteen-fold higher than maternal serum concentrations (1150 pg/ml). Corresponding fetal urine and cord serum concentrations were 16,781 and 2160 pg/ml, respectively. The amniotic fluid values are not influenced by fetal sex or maternal labor, nor do they correlate with amniotic fluid alpha-fetoprotein levels. However, there is a significant inverse correlation (r = -0.628; p less than 0.0001) between amniotic fluid prolactin and histidyl proline diketopiperazine after midgestation. The hypothesis that histidyl proline diketopiperazine may be a regulatory peptide for decidual prolactin production was tested by culturing term decidua in the presence of varying concentrations of histidyl proline diketopiperazine, but no inhibitory effect was observed. Decidual cultures did not produce measurable amounts of histidyl proline diketopiperazine. It is suggested that amniotic fluid histidyl proline diketopiperazine is derived from fetal urine. PMID- 2316581 TI - Amniotic fluid volume increase after amnioinfusion of a fixed volume. AB - Amnioinfusion of 250 ml of normal saline solution was performed in 30 laboring women at greater than or equal to 37 weeks' gestation with oligohydramnios as defined by an amniotic fluid index of less than or equal to 5 cm. A total of 50 amnioinfusions were performed. Amniotic fluid volumes, as assessed by the amniotic fluid index, increased by a mean of 4.3 +/- 1.5 cm after infusion. We conclude that in women with oligohydramnios, 250 ml of amnioinfusate will increase the amniotic fluid index by approximately 4 cm. PMID- 2316582 TI - Warning symptoms, uterine contractions, and cervical examination findings in women at risk of preterm delivery. AB - The presence of various reputed warning signs of preterm labor, the frequency of contractions, and the presence of cervical examination findings and their value in predicting preterm labor and spontaneous preterm delivery were assessed. The frequency of contractions and all cervical examination findings increased during pregnancy, as did backache, pressure, and cramping. The frequency of diarrhea, discharge, and bleeding remained constant. Of the various warning signs, only diarrhea and discharge were associated with the diagnosis of preterm labor. None of the warning signs were associated with spontaneous preterm delivery. Various patterns of contractions tended to be associated with higher rates of preterm labor and preterm delivery, but results were generally not statistically significant. Most cervical examination findings were statistically associated with both preterm labor and preterm delivery. PMID- 2316583 TI - Comparative evaluation of uterine response to exercise on five aerobic machines. AB - We evaluated the effect of five aerobic exercise machines on uterine activity during the third trimester of pregnancy. Uterine activity correlated with the type of exercise, but not with the level of exertion. At equivalent work loads, the bicycle ergometer led to uterine activity in 50% of sessions, the treadmill in 40%, the rowing ergometer in 10%, recumbent bicycle in 0%, and the upper arm ergometer in 0%. Therefore, the upper body ergometer and the recumbent bicycle appear to be the safest forms of aerobic exercise studied. PMID- 2316584 TI - Amniotic fluid alpha 1-antitrypsin concentration in premature rupture of the membranes. AB - Premature rupture of the membranes is probably a result of a loss in amniotic membrane collagen. A recent report that the concentration of alpha 1-antitrypsin was decreased in patients with premature rupture of the membranes suggested a generalized defect in such pregnancies. In this study we compared the concentration of alpha 1-antitrypsin in samples from pregnancies with premature rupture of the membranes and from pregnancies with preterm labor at similar gestational age. No difference in alpha 1-antitrypsin concentration was noted between these groups or between samples with or without intrauterine infection. These results support a localized inflammation and necrosis of the membranes at the site of rupture. PMID- 2316585 TI - A 62-year-old woman with endodermal sinus tumor of the ovary. AB - An endodermal sinus tumor of the ovary in a 62-year-old woman is described. This is the first case reported of which I am aware of endodermal sinus tumor of the ovary in a woman after the age of 60 years. PMID- 2316586 TI - Fetal acoustic stimulation in the early intrapartum period as a predictor of subsequent fetal condition. AB - Fetal acoustic stimulation has recently received much attention in the literature. This study evaluates fetal acoustic stimulation in the early intrapartum period as a predictor of subsequent fetal condition. The study group consisted of 201 patients, approximately 60% of whom had complicated pregnancies. All were in the latent phase of labor with singleton, vertex-presenting fetuses. Gestational age ranged from 37 to 43 weeks. Fourteen of the 201 fetuses (7%) showed a nonreactive response to fetal acoustic stimulation and those fetuses were at significantly greater risk of initial and subsequent abnormal fetal heart rate patterns, meconium staining, and cesarean delivery because of fetal distress and Apgar scores less than 7 at both 1 and 5 minutes. Transient fetal heart rate decelerations after a reactive response occurred in 25% of patients; however, fetal outcome was not worse in this group. A reactive response to fetal acoustic stimulation was associated with high specificity and negative predictive values. Therefore we conclude that fetal acoustic stimulation in the early intraprtum period may discriminate the compromised from the noncompromised fetus. PMID- 2316587 TI - Preoperative assessment of fragment D-dimer as a predictor of postoperative venous thrombosis. AB - We used a latex agglutination assay to measure preoperative plasma fragment D dimer levels in patients admitted to a gynecologic oncology service. Eight percent of 71 patients with gynecologic cancer had elevated fragment D-dimer levels; none of these patients developed postoperative deep venous thrombosis. Preoperative elevation of the fragment D-dimer level was not predictive of postoperative deep venous thrombosis. PMID- 2316588 TI - Acute renal failure in hypertensive disorders of pregnancy. Pregnancy outcome and remote prognosis in thirty-one consecutive cases. AB - The purpose of this study is to report short-term pregnancy outcome, subsequent pregnancy outcome, and remote prognosis (follow-up from 0.3 to 9.8 years) in 31 cases complicated by acute renal failure. Eighteen patients had "pure" preeclampsia and 12 patients (13 pregnancies) had chronic hypertension, parenchymal renal disease, or both before pregnancy. All patients had serial evaluation of renal function, urine microscopy, and electrolyte studies at the onset of acute renal failure and on follow-up. There were three immediate maternal deaths (two in the pure preeclampsia group and one in the other group). Nine patients (50%) in the "pure" group required dialysis during hospitalization and all 18 patients had acute tubular necrosis. Five patients (42%) in the other group required immediate dialysis and three patients had bilateral cortical necrosis. The majority of pregnancies in both groups were complicated by abruptio placentae and hemorrhage. All 16 surviving patients in the pure preeclampsia group had normal renal function on long-term follow-up (average 4.0 +/- 3.1 years). Conversely, nine of the 11 surviving patients in the second group required long-term dialysis on follow-up and four of them ultimately died of end stage renal disease. We conclude that proper management of acute renal failure in patients with pure preeclampsia-eclampsia does not result in residual function impairment. PMID- 2316589 TI - A longitudinal study of maternal digoxin-like immunoreactive substances in normotensive pregnancy and pregnancy-induced hypertension. AB - The serum of women in the third trimester of pregnancy demonstrates cross reactivity with some commercially available antibodies to digoxin. A number of studies have suggested that levels of this digoxin-like immunoreactive substance(s) are further increased in patients with pregnancy-induced hypertension, and some have proposed that the digoxin-like immunoreactive substance could be useful as a predictor of pregnancy-induced hypertension. We measured digoxin-like immunoreactive substance levels every 2 weeks throughout the third trimester in 170 women; of these, 20 developed hypertension. Digoxin like immunoreactive substance levels rose with gestational age. A graph of the slope of digoxin-like immunoreactive substance plotted against gestational age was fitted for the results obtained from each woman. There was no significant difference in the mean rate of increase of digoxin-like immunoreactive substance level per week between pregnancy-induced hypertension and normotensive pregnancy, nor was there any difference between these two groups at any gestational age studied. These results suggest that measuring digoxin-like immunoreactive substance levels is not useful as a predictor of pregnancy-induced hypertension. PMID- 2316590 TI - The use of nifedipine during the postpartum period in patients with severe preeclampsia. AB - Nifedipine is a calcium channel blocker that reduces blood pressure and increases renal blood flow. This double-blind investigation evaluated the effect of nifedipine in postpartum patients with severe preeclampsia. Thirty-one patients were randomized to receive either nifedipine (10 mg) or placebo every 4 hours beginning immediately after delivery. Data analysis revealed a significantly higher urine output in the nifedipine group during the first 24 hours after delivery (3834 versus 2057 ml; p less than 0.05). A significant reduction in mean arterial pressure was also noted in the nifedipine group between 18 and 24 hours postpartum (93.9 versus 100.2 mm Hg; p less than 0.05). There were no significant differences in the systolic or diastolic blood pressures, pulse, laboratory study results, or the need to administer hydralazine to control blood pressure. Nifedipine appears to have a beneficial effect on urinary output and mean arterial pressure during the first 24 hours post partum in patients with severe preeclampsia. PMID- 2316591 TI - Bacteriuria in the puerperium. Risk factors, screening procedures, and treatment programs. AB - Screening for bacteriuria by culture of voided midstream urine was done in 6803 puerperal women; significant growth was found in 8.1%. The urine was recollected by suprapubic aspiration and bacteriuria was confirmed in 52%, corresponding to an incidence of bladder bacteriuria of 3.7%. A history of past urinary tract infection, bacteriuria in pregnancy, operative delivery, epidural anesthesia, and bladder catheterization increased the risk of postpartum urinary tract infection. Only 21% of the women complained of dysuria; this symptom occurred significantly more often after operative delivery and in patients with previous urinary tract infection. Two hundred fifty-one women with bladder bacteriuria were subjected to different treatments by randomized allocation: 153 patients with amoxicillin susceptible bacterias were selected for amoxicillin treatment of 1, 3, and 10 days' duration. The cure rates were 84%, 94%, and 98%, respectively; the single dose therapy was significantly less effective than 10 days' treatment (p less than 0.05). Forty-six women with amoxicillin-resistant bacterial infections received cephalexin or nitrofurantoin therapy of 7 days' duration; the cure rate was 91%. Fifty-two women served as control subjects and received no treatment. Ten weeks later 27% still had persistent bacteriuria in their suprapubic aspiration control specimens. All therapeutic regimens except the single-dose method showed a cure rate that was significantly higher than the spontaneous cure rate (p less than 0.05). Multiparity seemed to be a predisposing factor for persistence of bacteriuria. The study indicates that puerperal patients with positive midstream urine specimens should not be automatically treated, but more thoroughly examined. In cases of confirmed bladder bacteriuria, treatment should be recommended; 3 days' therapy appears to be sufficient. PMID- 2316593 TI - Production of prostaglandin E2 by human amnion in vitro in response to addition of media conditioned by microorganisms associated with chorioamnionitis and preterm labor. AB - To examine the potential role of bacterial infection in the cause of spontaneous preterm labor, human amnion cells in tissue culture were exposed to medium conditioned by culturing each of 21 microorganisms previously found in association with chorioamnionitis and preterm labor. At a final concentration of 0.1% bacterial conditioned medium, a significant stimulation of prostaglandin E2 production from amnion cells was observed for this range of microorganisms. Conditioned medium obtained from culturing Bacteroides fragilis caused a dose related increase in prostaglandin production, final concentrations of 0.02% to 0.1% being stimulatory but greater concentrations (0.1% to 10%) causing a progressive inhibition of prostaglandin synthesis. A similar concentration related response in which stimulation was followed by inhibition occurred on addition of increasing concentrations of phospholipase A2 to amnion cells. These data suggest that bacterial phospholipase may release arachidonic acid from amnion leading to prostaglandin E2 synthesis, but excessive addition of phospholipase and consequent increased arachidonic acid availability may give rise to substrate inhibition of cyclooxygenase enzyme and inhibit prostaglandin E2 synthesis. Overall it appears that a wide variety of microorganisms associated with preterm labor may secrete phospholipase, which liberates amnion arachidonic acid for conversion to the oxytocic agent prostaglandin E2. PMID- 2316592 TI - Prediction of residual trophoblastic tissue in first-trimester abortions and low levels of human chorionic gonadotropin beta-subunit. AB - The clinical data and the histologic report of curettage specimens of 174 patients with first-trimester abortion and human chorionic gonadotropin beta subunit less than 500 mIU/ml were reviewed. In only 22 (12.6%) were chorionic villi histologically reported. A multivariate analysis showed that increased log human chorionic gonadotropin beta-subunit levels within the range of 20 to 500 mIU/ml, intrauterine tissue demonstrated by ultrasonography, higher gestational age, and active bleeding were significant predictive variables for the presence of villi in curettage specimens. A mathematical formula and a clinical scoring system for the prediction of residual villi in these cases were devised and were applied to the data of our study group. The sensitivity, false-negative rate, and specificity of the scoring system were 90.9%, 2.2%, and 59.2%, respectively; however, the false-positive rate was 75.6%. By use of this scoring system in patients with first-trimester abortion and low human chorionic gonadotropin beta subunit level, the presence of villi in curettage specimens can thus be predicted with a high sensitivity and as many as 60% of curettage procedures might be prevented. PMID- 2316594 TI - A longitudinal study of respiratory changes in normal human pregnancy with cross sectional data on subjects with pregnancy-induced hypertension. AB - Respiratory frequency, tidal volume, minute ventilation, oxygen consumption, carbon dioxide production, and end-tidal carbon dioxide tension were measured longitudinally during pregnancy and post partum in 20 normal subjects with a computer-assisted mass spectrometer. Resting tidal volume, minute ventilation, oxygen consumption, and carbon dioxide production increased during pregnancy. End tidal carbon dioxide tension fell progressively during pregnancy. Respiratory exchange ratio was 0.9 at 36 to 39 weeks' gestation and 0.8 at 5-13 weeks post partum. Respiratory frequency did not change during pregnancy. The increase in minute ventilation is in excess of the increase of carbon dioxide production and the resultant fall in end-tidal carbon dioxide tension reflects a fall in systemic arterial blood carbon dioxide tension. The greater respiratory exchange ratio during late pregnancy as compared with post partum also reflects this hyperventilation during pregnancy. Fourteen subjects with pregnancy-induced hypertension studied cross-sectionally failed to show any difference in the respiratory variables measured when compared with normotensive subjects at a similar length of gestation. PMID- 2316595 TI - The relationship between experimentally determined litter size and maternal blood pressure in spontaneously hypertensive rats. AB - Pregnancy lowers blood pressure in hypertensive rats. To evaluate the role of the conceptus in maternal blood pressure regulation, we measured the changes in systolic blood pressure b (by tail-cuff plethysmography) throughout gestation and mean arterial pressure, cardiac output, and organ blood flows (with radioactive microspheres) on postmating day 21 for calculation of total peripheral and organ vascular resistances in spontaneously hypertensive rats with litter size surgically adjusted to 0 to 10 conceptuses on postmating day 7. Blood pressure remained elevated in those rats with zero fetuses but decreased during the last week of pregnancy in those rats with three or more fetuses. The magnitude of the decrease was directly related to litter size. At term, cardiac output was positively correlated (r = 0.61; p less than 0.001), whereas mean arterial pressure and total peripheral resistance were negatively correlated (r = -0.74; p less than 0.001 and r = -0.79; p less than 0.001, respectively) with litter size. Resistances of all the vascular beds in the body, except the kidneys, spleen, and hepatic artery were also negatively correlated with fetal number. Thus pregnancy is characterized by a generalized maternal vasodilation, and the fetal/placental unit may play a significant role in modulating maternal vascular tone. PMID- 2316597 TI - Value of hamster egg penetration assay. PMID- 2316596 TI - Deoxyribonucleic acid flow cytometric analysis of cervical adenocarcinoma: prognostic significance of deoxyribonucleic acid ploidy and S-phase fraction. AB - Paraffin-embedded tumor samples from 125 patients with cervical adenocarcinoma were analyzed by deoxyribonucleic acid flow cytometry. Thirty-one percent of the tumors were aneuploid. Triploid deoxyribonucleic acid content predominated (51.3%) and one third of the deoxyribonucleic acid aneuploid tumors were tetraploid, whereas near-diploid deoxyribonucleic acid aneuploidy was seen infrequently. Deoxyribonucleic acid aneuploidy was associated with tumor size, histologic grade, clinical stage, and high S-phase fraction. Deoxyribonucleic acid ploidy and S-phase fraction value were independent prognostic parameters, together with the presence of lymph node metastases and tumor size. In conclusion, our results indicate that flow cytometric deoxyribonucleic acid analysis helps to predict the prognosis and may thus influence the choice of treatment. PMID- 2316598 TI - Low segment cesarean section: a supracervical hysterotomy. PMID- 2316599 TI - Hormone activity and autoimmune function. PMID- 2316600 TI - Ammonium chloride pretreatment of bloody amniotic fluids for cytogenetic analysis. PMID- 2316601 TI - Heparin prophylaxis during pregnancy. PMID- 2316602 TI - Predictive value and prevalence. PMID- 2316603 TI - Lack of association of cytotoxicity in serum and preeclampsia. PMID- 2316604 TI - Premature ovarian failure. PMID- 2316605 TI - Methodologic queries: clinical significance of mean arterial blood pressure in second trimester. PMID- 2316606 TI - The transformation of HIV infection and AIDS in occupational therapy: beginning the conversation. PMID- 2316607 TI - Knowledge and attitudes of occupational therapy students regarding AIDS. AB - In this pilot study, knowledge regarding AIDS was tested in 36 occupational therapy students and 33 education students. Also measured were the students' attitudes toward AIDS patients and the resulting health care controversies. An analysis of the results revealed no significant differences in knowledge between the two groups. Attitudinal differences between the two groups, however, were significant for two items. Implications for occupational therapy curricula are discussed. PMID- 2316608 TI - Occupational therapy personnel and AIDS: attitudes, knowledge, and fears. AB - This study explored the attitudes, knowledge, and fears of occupational therapists and certified occupational therapy assistants regarding AIDS and HIV. The 119 respondents' scores related to knowledge and fear revealed that many had significant fears about AIDS, which in turn may inhibit their willingness to care for persons with AIDS. The respondents also indicated a need for specific information about the condition, including current research data and information on infection control. PMID- 2316609 TI - Assessing the impact of HIV disease. AB - This article presents a definition of HIV disease as a four-stage process. The Sickness Impact Profile (SIP) (Bergner, Bobbitt, Carter, & Gilson, 1981) was used to measure behavioral dysfunction in a sample of 15 persons with Stage 3 or Stage 4 (symptomatic) HIV disease. The areas of work, leisure, cognitive behavior, and emotional behavior were found to be, on the average, most affected by HIV disease. A diagnosis of AIDS does not affect the severity of dysfunction. Functional deficits that are experienced for longer periods of time affect several behavioral categories on the SIP as well as on the overall SIP score. PMID- 2316610 TI - Hemophilia, AIDS, and occupational therapy. AB - This article describes the blood clotting disorder of hemophilia, including its transmission, incidence, and physical and psychosocial effects. The epidemiology of persons with both hemophilia and HIV are discussed, as well as HIV's rapid spread due to contaminated blood products and the mechanisms commonly used to cope with HIV infection. Specific suggestions on occupational therapy intervention are provided, including helping clients learn to cope with HIV by transferring skills previously learned for coping with hemophilia; teaching stress reduction, anger management, communication, and energy conservation skills; educating families and helping them set appropriate goals; designing adaptive systems for dealing with neurological deficits; and designing exercise programs. PMID- 2316611 TI - A day treatment program for persons with AIDS. AB - This paper describes the Village Nursing Home's day treatment program for persons with AIDS, with an emphasis on the role of occupational therapy and the outcomes of occupational therapy interventions. The clients' demographics are included, and a general program philosophy of clients' empowerment is discussed. The health promotion framework and the use of holistic modalities address the spiritual aspect of the individual and how occupational therapy and spirituality might interconnect. PMID- 2316612 TI - The ethics of caring for patients with HIV or AIDS. AB - Health care professionals encounter many ethical issues in the care of persons who are HIV positive or who have been diagnosed as having AIDS. Such issues include the allocation of scarce resources for research and health care; the use of various methods of disease control, including mandatory testing, forced isolation, informing of sexual partners, and education; and the determination of the responsibility to treat infected patients. These issues are presented as a stimulus to readers to examine their own attitudes regarding HIV and AIDS. The usefulness and limitations of occupational therapy's professional code in resolving ethical dilemmas are discussed, followed by the description of a process that can be used to analyze and solve these dilemmas. PMID- 2316613 TI - A legal perspective on AIDS. AB - AIDS presents difficult and unprecedented legal problems. Because modern law requires that persons with disabilities or illnesses be integrated into the mainstream of society, past responses to those with communicable diseases are no longer acceptable. Laws dealing with AIDS patients will have to evolve gradually and build upon commonsense solutions to problems. PMID- 2316614 TI - Occupational therapy for children with perinatal HIV infection. AB - This article discusses occupational therapy for children with perinatal HIV infection and their care-givers. An interdisciplinary early intervention and preschool program serving these children is described. Current medical and neurological research is reviewed to serve as a basis for occupational therapy intervention. Therapeutic approaches that integrate physical, neurological, developmental, and psychosocial needs are presented. PMID- 2316615 TI - The model of human occupation and adults with HIV infection and AIDS. AB - HIV infection affects all aspects of a person's occupational functioning. This article examines the application of the Model of Human Occupation (Kielhofner & Burke, 1980) to adults with HIV. An occupational therapy assessment battery based on the model is introduced. Given the physical, psychosocial, and environmental needs of persons with HIV, the assessment must be comprehensive to fully evaluate the effect of HIV on occupational behaviors. Goal planning and treatment follow the assessment process. A case example illustrates the integration of the Model of Human Occupation with clinical practice. PMID- 2316616 TI - Coping with grief in response to caring for persons with AIDS. AB - AIDS has or will affect virtually every professional health care provider. Occupational therapists are in a key position to identify and intervene with the social and occupational changes and losses commonly experienced by this patient population. Suggestions are provided to assist occupational therapists in helping patients with AIDS maintain meaning in their lives. Strategies to help occupational therapists prevent burnout resulting from the emotional stress related to caring for patients with AIDS are suggested as well. PMID- 2316617 TI - AIDS: toward a compassionate response. AB - AIDS evokes powerful feelings, often manifestations of fear, among health care providers. To effectively treat patients with AIDS, occupational therapists must acknowledge and reconcile their personal feelings. One way to formulate a compassionate response to patients is to understand the meanings that we give to AIDS, meanings that shape our interpersonal behaviors. Restricted meanings--that the disease constitutes death, sin, crime, war, or community division--place the person with AIDS at risk for compromised care. Recognizing the limitations of these meanings can free therapists to find other meanings that inspire compassion. PMID- 2316618 TI - The HIV-positive intravenous drug abuser. PMID- 2316619 TI - Teaching safe sex practices to psychiatric patients. PMID- 2316620 TI - The demonstration of vasodilator activity of pancreatic amylin amide in the rabbit. AB - Amylin amide, a 37-amino acid peptide that is a major component of amyloid deposits in the diabetic pancreas, possesses vasodilator activity. Human synthetic amylin amide (30 to 300 pmol/site) stimulated a dose-dependent increase in blood flow after intradermal injection in rabbit skin. Amylin amide was 100 times less active than the structurally related potent vasodilator neuropeptide calcitonin gene-related peptide. Amylin amide did not induce edema formation; however, as a consequence of its vasodilator activity, amylin amide potentiated edema formation induced in rabbit skin by bradykinin. The intravenous injection of amylin amide (10 nmol) caused a systemic drop in blood pressure. This study demonstrates that amylin amide elicits vasodilator responses in vivo. It is possible that the release of amylin amide from the pancreas in type II diabetes could lead to changes in vascular tone. PMID- 2316621 TI - Ischemia-reperfusion in humans. Appearance of xanthine oxidase activity. AB - We evaluated effluent blood from extremities of human patients undergoing reconstructive surgical treatment, which is routinely accompanied by upper extremity exsanguination and application of a tourniquet, resulting in total interruption of arterial blood flow to one upper extremity. After tourniquet release (reperfusion), there were immediate increases in the plasma levels of xanthine oxidase activity, uric acid, and histamine in the ipsilateral limb and much smaller increases, if any, in levels of the same materials in plasma obtained from the contralateral extremity. There was no detectable xanthine dehydrogenase activity in plasma from either limb. Plasma also contained evidence of products consistent with the formation of oxygen-derived free radicals, namely, the appearance predominantly in the reperfused limb of hemoglobin and fluorescent compounds. These data indicate for the first time in humans that ischemia-reperfusion events are associated with the appearance of xanthine oxidase activity and its products in the plasma effluent. PMID- 2316622 TI - Carcinoma in situ of the testis. Detection of malignant germ cells in seminal fluid by means of in situ hybridization. AB - Testicular germ cell tumors can be prevented if the neoplasia is diagnosed at the stage of carcinoma in situ (CIS). Hyperdiploid DNA content is one of the markers of CIS germ cells. We developed a noninvasive procedure for detection of CIS of the testis by means of a nonradioactive in situ hybridization assay with a probe for chromosome 1. Seminal cytospin smears from 2 men with isolated CIS changes, from 6 men in whom CIS was combined with a tumor, and from 16 control men without evidence of testicular neoplasia were tested. Ejaculates from men with CIS contained on average 2.6% hyperdiploid cells, whereas the corresponding percentage in the smears from controls was 0.2 (P = 0.009). In a blind study we identified samples from both patients with isolated CIS changes and from 3 of the 6 men in whom CIS was accompanied by a tumor, based on the percentage of the hyperdiploid cells. No false-positive results were obtained. Thus this study confirmed findings of previous immunocytochemical and flow cytometric studies that indicated exfoliation of CIS germ cells into seminal fluid. For detection of aneuploid cells in semen, in situ hybridization may be a more sensitive technique than flow cytometry. Applied on seminal samples, in situ hybridization may become a valuable and fast tool for diagnosis of CIS and thereby for prevention of testicular cancer. PMID- 2316623 TI - Monoclonal antibody HML-1, a marker for intraepithelial T cells and lymphomas derived thereof, also recognizes hairy cell leukemia and some B-cell lymphomas. AB - Current views regard monoclonal antibody HML-1 as an exquisite marker for intraepithelial T cells and primary intestinal and cutaneous T-cell lymphomas. We show that HML-1 reacted with 11 of 12 cases of hairy cell leukemia, with 1 of 13 cases of primary gastrointestinal B-cell lymphoma, and with an unclassified large cell B lymphoma of the thoracic wall. We conclude that HML-1 is not restricted to the T-cell lineage and that the HML-1 antigen is expressed in a small subset of both T- and B-cell neoplasms. PMID- 2316624 TI - Prevention of 11-deoxycorticosterone-salt-induced glomerular hypertrophy and glomerulosclerosis by dietary phosphate binder. AB - The effects of dietary phosphate binder on deoxycorticosterone (DOC)-salt hypertensive rats were examined. DOC-treated and non-DOC-treated rats were fed the diet either with or without phosphate binder, dihydroxyaluminum aminoacetate. All rats drank 1% NaCl. DOC-salt-treated rats without binder demonstrated marked glomerular hypertrophy, many globally sclerosed glomeruli, severe proteinuria, focal cardiac fibrosis, and splenomegaly. A significant reduction of glomerular hypertrophy, glomerulosclerosis, severity of proteinuria, splenomegaly, and the myocardial lesion took place when the DOC-salt-treated rats were given phosphate binder. The globally sclerosed glomeruli exhibited remarkable hypertrophy while structurally preserved glomeruli showed little evidence of enlargement. The plasma phosphate level was low in rats with dietary phosphate binder. In conclusion, the dietary phosphate binder ameliorated glomerular hypertrophy, glomerulosclerosis, proteinuria, myocardial fibrosis, and splenomegaly occurring in DOC-salt-treated rats. The data indicated that there was an association between glomerular hypertrophy and glomerulosclerosis in this model. The exact mechanisms of action of the phosphate binder, however, remain far from clear. PMID- 2316625 TI - Reversal of inhibition of rat glomerular epithelial cell growth by growth factors. AB - The ability of several growth factors to reverse heparin-induced inhibition of rat glomerular epithelial cell (GEC) growth and the mechanism of growth inhibition were explored in vitro. Insulin-like growth factor-1, rat multiplication-stimulating activity, and platelet-derived growth factor had no effect on proliferation of cultured GEC exposed to heparin (100 micrograms/ml). Epidermal growth factor (EGF) partially reversed heparin-induced growth inhibition in a dose-dependent fashion with a maximum effect seen at 1 ng/ml. No additive effect was seen with combinations of EGF and the other growth factors assayed. A decrease in EGF-stimulated incorporation of 3H-thymidine by GEC was seen with as little as 2 hours of heparin exposure and persisted for up to 48 hours. Heparin consistently increased binding of 125I-EGF to GEC with a significant increase apparent after 2 hours of exposure and a further increase with a 24-hour exposure. Increased EGF binding to heparin-treated cells was due to a significant increase in the association constant of EGF and its receptor with no effect on receptor number. Interactions between GEC and heparinlike glycosaminoglycans in the glomerular basement membrane may play a role in the regulation of GEC proliferation in normal and diseased states. PMID- 2316626 TI - Macrophage secretory products selectively stimulate dermatan sulfate proteoglycan production in cultured arterial smooth muscle cells. AB - Arterial dermatan sulfate proteoglycan has been shown to increase with atherosclerosis progression, but factors responsible for this increase are unknown. To test the hypothesis that smooth muscle cell proteoglycan synthesis may be modified by macrophage products, pigeon arterial smooth muscle cells were exposed to the media of either cholesteryl ester-loaded pigeon peritoneal macrophages or a macrophage cell line P388D1. Proteoglycans radiolabeled with [35S]sulfate and [3H]serine were isolated from culture media and smooth muscle cells and purified following precipitation with 1-hexadecylpyridinium chloride and chromatography. Increasing concentrations of macrophage-conditioned media were associated with a dose-response increase in [35S]sulfate incorporation into secreted proteoglycans, but there was no change in cell-associated proteoglycans. Incorporation of [3H]serine into total proteoglycan core proteins was not significantly different (5.2 X 10(5) dpm and 5.5 X 10(5) disintegrations per minute (dpm) in control and conditioned media-treated cultures, respectively), but selective effects were observed on individual proteoglycan types. Twofold increases in dermatan sulfate proteoglycan and limited degradation of chondroitin sulfate proteoglycan were apparent based on core proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Immunoinhibition studies indicated that interleukin-1 was involved in the modulation of proteoglycan synthesis by macrophage-conditioned media. These data provide support for the role of macrophages in alteration of the matrix proteoglycans synthesized by smooth muscle cells and provide a mechanism to account for the reported increased dermatan sulfate/chondroitin sulfate ratios in the developing atherosclerotic lesion. PMID- 2316627 TI - Pentoxifylline-induced modulation of human leukocyte function in vitro. AB - We previously demonstrated that pentoxifylline stimulated leukocyte migration in vitro and leukocyte accumulation in vivo and protects neonatal mice from experimentally induced Staphylococcus aureus infections. In the present studies we have investigated pentoxifylline's effect on human leukocyte function in vitro. In these studies we demonstrate that pentoxifylline at low concentrations (ie, 0.01 and 0.1 mg/ml) stimulates both leukocyte migration and microbicidal activity in vitro. Alternatively, low concentrations (0.001 to 0.1 mg/ml) of pentoxifylline had no significant effect on the binding uptake of S. aureus by leukocytes, nor did it enhance phagocytic degranulation. At extremely low concentrations (0.001 mg/ml), pentoxifylline enhanced oxygen metabolism by human leukocytes, as reflected by increased H2O2 production and chemiluminescence (CL). At higher concentrations (ie, 0.1 to 1 mg/ml), pentoxifylline consistently suppressed these leukocyte functions in vitro. Thus, this study supports the following hypothesis: 1) the in vivo effects of pentoxifylline may involve a direct effect on both leukocyte mobilization and microbicidal activity, and 2) the enhanced microbicidal activity induced by pentoxifylline may be a result of enhanced leukocyte oxygen metabolism. In summary, pentoxifylline appears to be an interesting immunomodulator (ie, immunoenhancement and immunosuppression) of leukocyte function in vitro, but additional studies will be required before the efficacy of pentoxifylline in man can be determined. PMID- 2316628 TI - Expression of human tumor-associated antigens in pancreatic cancer induced in Syrian hamsters. AB - Our previous studies have shown that pancreatic cancer induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) shows remarkable similarities with the human disease in morphologic and biologic characteristics. Moreover, both human and hamster pancreatic cancer share expression of some tumor-associated antigens, such as those with blood group specificities, including A, B, H, Leb, Lex, and Ley. By examining other antigens commonly expressed in human pancreatic cancer, we have found that monoclonal antibodies CO17-1A (recognizing 17-1A antigen), OC 125 (recognizing CA 125 antigen), B72.3 (recognizing TAG-72 and DU-PAN-2 react with induced pancreatic cancer in a pattern similar to that seen in human pancreatic cancer. Remarkably, although the epitopes of the antigens recognized by these three antibodies are different, many tumor cells were reactive with all these antibodies. However, in contrast to the human cancer, none of these antigens were expressed in the normal hamster pancreatic tissue, except for 17 1A. However, all of these antigens were expressed in some hamster tissues showing the same cellular localization as pancreatic cancer cells and corresponded, to a great extent, with findings in human tissue. Expression of these antigens was diminished in vitro (cell culture) but was regained in vivo (homologous transplantation). The results emphasize the usefulness of this experimental model for studying some aspects of tissue antigenicity, particularly as it relates to pancreatic cancer. PMID- 2316629 TI - Triamcinolone acetonide-induced meningocele and meningoencephalocele in rhesus monkeys. PMID- 2316630 TI - Polarized insertion of an intracellular glycoprotein pool into the apical membrane of MDCK cells. AB - A monoclonal antibody that recognizes a 135-kDa glycoprotein (GP135) on the apical membrane of Madin-Darby canine kidney (MDCK) cells was used to identify and characterize an intracellular pool of GP135. Mild trypsin treatment at 4 degrees C removed approximately 95% of the GP135, and after warming to 37 degrees C, the reappearance of GP135 on the apical membrane was monitored by radioimmunoassay. Incorporation of GP135 into the apical cell surface after trypsin treatment consisted of two components, a rapidly inserted, cycloheximide insensitive portion (defined as the GP135 pool), which leveled off within 1 h, followed by a slower insertion of newly synthesized GP135. Immunogold electron microscopy demonstrated that the GP135 pool was targeted in a polarized manner and was only detected on the apical membrane. Temperature shift and retrypsinization experiments provided evidence that the GP135 pool consisted of intracellular vesicles that could fuse with the plasma membrane. This was confirmed by immunofluorescence microscopy demonstrating that GP135 was localized within large cytoplasmic vesicles residing at varying distances from the apical cell surface. These data provide evidence for the presence of a regulated pathway in MDCK cells and support the possibility that the GP135 pool functions as an intracellular reserve which can exhibit polarized insertion into the plasma membranes similar to that described for other epithelial cells. PMID- 2316631 TI - Free radical injury to skeletal muscles of young, adult, and old mice. AB - We tested the hypotheses that 1) muscles of old mice are more susceptible to injury than muscles of young and adult mice, and 2) secondary or delayed onset injury results from free radical damage. Extensor digitorum longus muscles were injured in situ by lengthening contractions. Injury was assessed by measurement of maximum isometric tetanic force (Po) expressed as a percentage of the control value and by morphological damage. Mice were treated with a free radical scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD). Three days postinjury, the Po of 44% for muscles of nontreated old mice was significantly lower than the Po of 58 and 61% for those of young and adult mice. In each group, the secondary injury at 3 days was alleviated by treatment with PEG-SOD. For treated muscles of young, adult, and old mice, values for Po were 88, 80, and 70%, respectively. We conclude that muscles of old mice are more susceptible to injury than muscles of young or adult mice and that free radicals contribute to the secondary or delayed onset injury. PMID- 2316632 TI - Contraction-induced injury: recovery of skeletal muscles in young and old mice. AB - We tested the hypothesis that after the same amount of contraction-induced injury, skeletal muscles in old mice regenerate less well than muscles in young mice. Extensor digitorum longus (EDL) muscles in young and old mice were exposed to 15 min of lengthening contractions. The amount of injury was evaluated at 3, 7, 14, 28, and 60 days by measurements of maximum isometric tetanic force (Po) and number of fibers per cross section. When values 3 days after lengthening contractions were expressed as a percentage of control values, the Po (approximately 34%) and fiber number (approximately 80%) for muscles in old mice were not different from those in young mice, suggesting that muscles in old and young mice were injured to the same degree. By 28 days, injured muscles in young mice regained control values for Po and fiber number. In contrast, at 28 days, injured muscles in old mice recovered approximately 84 and approximately 87% of control values for Po and fiber number, respectively, and deficits in Po persisted at 60 days. We conclude that injured muscles regenerate less well in old mice than in young mice. PMID- 2316633 TI - Taurine transport by microvillous membrane vesicles and the perfused cotyledon of the human placenta. AB - Human placental uptake and maternal-to-fetal (M-to-F) net transfer of taurine were evaluated in purified microvillous membrane vesicles (MMV) and the isolated perfused cotyledon. Taurine uptake by MMV was specifically stimulated by an inward Na+ gradient [maximum velocity (Vmax), 24.5 +/- 0.6 pmol.mg-1.30 s-1; Michaelis constant (Km), 6.2 +/- 0.7 microM], with uptake stoichiometry showing approximately 2 Na+/taurine molecule. In the presence or absence of Na+, Cl- did not stimulate uptake. Na(+)-stimulated uptake was enhanced by an outward K+ gradient. beta-Alanine and hypotaurine competitively inhibited uptake of taurine in MMV. Two-way uptake inhibition studies showed no interaction between taurine and non-beta-amino acids. When MMV were preloaded with taurine there was enhancement of Na(+)-stimulated uptake. In the perfused placentas, saturable M-to F net transfer of taurine was not observed, despite saturation of tissue uptake from the maternal circulation. During 3 h of perfusion, no fetal-to-maternal (F to-M) gradient formed for taurine; yet, a 2:1 gradient simultaneously occurred for histidine. This study demonstrates that taurine uptake by the microvillous membrane of the human placenta is highly specific, of high affinity, and Na+ coupled. PMID- 2316634 TI - Augmentation of GABA-induced current in frog sensory neurons by pentobarbital. AB - The effect of pentobarbital sodium (PB) on the gamma-aminobutyric acid (GABA) induced macroscopic and microscopic Cl- currents (ICl and iCl, respectively) was studied in the soma membrane of isolated frog sensory neurons using a rapid concentration-jump and patch-clamp technique. The GABA-induced ICl was composed of a transient peak and a steady plateau. PB shifted the concentration-response curve of the GABA-induced peak ICl to the left without affecting the maximum value. The apparent dissociation constant (KD) decreased from 13 microM at control to 8.0, 4.8, and 2.9 microM by adding 10, 30, and 100 microM PB, respectively. PB also shifted the concentration-response curve for the plateau ICl to the left and augmented the maximum value of the plateau, indicating an increase in the available receptor-channel complex. The Hill coefficient (n = 2) in concentration-response curves of both peak and plateau responses was not changed by adding PB. Both the activation and desensitization phases of GABA induced ICl consisted of two exponential components. PB significantly increased the time constant of slow desensitization component at all concentrations of GABA used. In the "inside-out" configuration, PB markedly increased the open probability (Po) of a GABA-gated single Cl- channel having a conductance of 14.57 +/- 2.3 pS (n = 123) without affecting the single-channel conductance. The increase of Po was due to the prolongation of mean open time (tau of the tau os) and shortening of mean closed time (tau cf and tau cs), resulting in the increase of channel-opening events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316635 TI - Corticosterone 6 beta-hydroxylase in A6 epithelia: a steroid-inducible cytochrome P-450. AB - We found microsomal corticosterone 6 beta-hydroxylase (6 beta-OHase) from cultured A6 kidney epithelial cells to be a cytochrome P-450 enzyme with both similarities to and differences from the rat liver steroid 6 beta-OHase P-450p. Enzyme activity was inhibited by CO, alpha-naphthoflavone, metyrapone, and clotrimazole, well-known inhibitors of P-450 enzymes, and increased by known inducers of P-450 enzymes, including dilantin, phenobarbital sodium, and corticosteroids. Moreover, some additional, relatively specific inducers of P 450p (troleandomycin and pregnenolone-16 alpha-carbonitrile) also induced the A6 6 beta-OHase, whereas inducers of other forms of P-450 (aroclor, spironolactone, and isosafrole) appeared to repress the A6 enzyme. The time course of increase in enzyme activity and increased cellular cytochrome P-450 content were consistent with increased levels of enzyme protein. Induction of 6 beta-OHase by the substrate (corticosterone), the metabolite (6 beta-OH-corticosterone), dexamethasone, and aldosterone was biphasic as a function of inducer concentration, with approximate 50% effective concentration (EC50) values of 10( 8)-10(-9) M and 10(-5)-10(-6) M for the respective components of induction. Cortisol also induced the enzyme at 10(-8)-10(-6) M; however, its metabolite 6 beta-OH-cortisol was ineffective or decreased activity at higher concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316636 TI - Vector-free gravity disrupts synapse formation in cell culture. AB - Terrestrial organisms evolved under and are subjected to the constancy of gravity. The organisms having adapted to this environmental factor, it is possible that embryonic development may be modified by exposure to altered gravity. To test the effects of gravity on embryonic development, we monitored the formation of nerve-associated acetylcholine receptor patches (NARPs) as an index of synaptogenesis. Embryonic spinal neuron and myotomal myocyte cocultures were placed in a horizontally rotating clinostat. From the cell's perspective, this results in the cancellation of the gravitational vector because of continuous averaging, thus mimicking the reduced gravitational force encountered in space. NARPs from cultures in which nerve-muscle contact was established before the onset of rotation were unaffected. In contrast, cultures in which nerve contact took place during rotation showed a marked inhibition of NARPs. Moreover, in the myocytes which did exhibit NARPs, the area of the patch was significantly reduced compared with control sister cultures. Several paradigms were used to ascertain that these findings did not result simply from loss of contact between neurites and myocytes, accelerated diffusion of a putative aggregating factor secreted by neurites, or from turbulence in the medium. Our data suggest that the process of synapse formation is sensitive to the gravitational vector. Embryonic development of the nervous system, in space, may therefore be markedly different from that normally occurring on earth. PMID- 2316637 TI - The polyphasic nature of the respiratory process at the mitochondrial level. AB - The kinetics of oxygen consumption by rat liver mitochondria, respiring under a variety of metabolic conditions, have been studied. Respiration was initiated by injecting oxygen into anaerobic suspensions of mitochondria. It was found that, irrespective of the metabolic state of the mitochondria and the nature of the respiratory substrate, the rates of electron flow and oxygen consumption follow the pattern of a polyphasic reaction. The rates of oxygen uptake during the first phase are extremely fast and depend on oxygen concentration. The second phase represents a transition in which net oxidation of cytochrome-c oxidase stops and the rates of oxygen consumption suddenly decrease. The third phase is characterized by its changeability. Depending on initial conditions the rates may increase, decrease, or remain constant, although the reaction is not one of zero order. During the last phase, the rates decrease and the oxidase becomes increasingly reduced. It is postulated that the mitochondrial respiratory process is basically a cyclic event in which the redox state of the membrane and the rates of oxygen consumption oscillate with amplitudes and frequencies conditioned by the energy demand and energy-yielding capacity of the cell. PMID- 2316638 TI - Mechanics of K(+)-induced isotonic and isometric contractions in isolated canine coronary microarteries. AB - The effects of shortening in isotonic contractions on the mechanics of microvascular smooth muscle were investigated. Intramyocardial canine coronary microarteries (in situ diameter 60 +/- 3 microns) were mounted as rings, connected to a newly developed photoelectromagnetic force-length transducer, and activated with 125 mM K+. Shortening during isotonic contractions depressed the length-force relation (shortening deactivation) compared with the length-force relation obtained from isometric contractions; the effect was present at the earliest moments after activation, suggesting that a fundamental mechanism associated with the actual sliding of contractile filaments delayed onset of contractile activity in isotonic contractions compared with isometric contractions. Force-velocity relations were obtained by isotonic quick releases from isotonic and isometric contractions at various times. Isotonic shortening before the quick releases reduced the constants of the apparent hyperbolic force velocity relations and maximal velocity of shortening (Vmax) compared with isometric contractions released at the same time. Increasing contraction duration reduced Vmax but more so in isotonic than in isometric contractions. Vmax also decreased with decreasing instantaneous length. A possible effect of force development on Vmax before the isotonic quick release was also described. Quick increments of load during isotonic contractions were sustained during active shortening in the phasic part, but during the tonic part loading resulted in a pronounced transient relaxation. Thus, in microvascular preparations, active isotonic shortening altered the length-force, force-velocity, and velocity-time relations and uncovered a time-dependent sensitivity to loading conditions. These experiments suggested that the mechanics of smooth muscle contraction may contribute significantly to the mechanisms of the physiological control of coronary microvascular diameter. PMID- 2316639 TI - Histamine receptors in human fibroblasts: inositol phosphates, Ca2+, and cell growth. AB - Histamine stimulated inositol phosphate formation by human skin fibroblasts. The effect of histamine was reduced but still readily apparent in the absence of extracellular Ca2+. Histamine caused a transient increase in intracellular free Ca2+ as detected by indo-1 and fura-2 fluorescence studies on cell populations and on individual cells. Similar increases were observed in the absence of extracellular Ca2+, indicating that the effect was primarily due to mobilization of Ca2+ from intracellular stores, presumably by inositol trisphosphate (IP3). The effects of histamine on phosphoinositide metabolism and intracellular Ca2+ were inhibited by pretreatment of the cells with phorbol esters, suggesting that the histamine receptor in fibroblasts is subject to feedback regulation by protein kinase C. Histamine inhibited the incorporation of [3H]-thymidine into DNA. The effects of histamine on inositol phosphate formation, intracellular Ca2+, and thymidine incorporation were blocked by the H1 receptor antagonist mepyramine. Our results indicate that human skin fibroblasts have H1 receptors coupled to the formation of inositol phosphates and mobilization of intracellular Ca2+. We suggest that this H1 receptor also mediates a block of the cell cycle and that histamine may play a physiological role in the regulation of fibroblast proliferation. PMID- 2316641 TI - Stimulation of porcine thyroid cell alkalinization and growth by EGF, phorbol ester, and diacylglycerol. AB - We studied the effects of epidermal growth factor (EGF), 12-O tetradecanoylphorbol-13-acetate (TPA), and 1-oleoyl-2-acetyl-glycerol (OAG) on cytoplasmic pH (pHi) and cell growth in cultured porcine thyroid cells. pHi was measured using 2',7'-bis(2-carboxyethyl-5,6-carboxyfluorescein (BCECF), an internalized fluorescent pH indicator. EGF, TPA, and OAG alkalinized the thyroid cells and stimulated their growth. These EGF-, TPA-, and OAG-stimulated cell alkalinization and growth depended on extracellular Na concentrations and were inhibited by amiloride, an inhibitor of Na(+)-H+ exchanger, indicating that EGF-, TPA-, and OAG-stimulated cell alkalinization and growth may occur through activation of Na(+)-H+ exchange. Alkalinization seems to be involved in thyroid cell growth. TPA (a tumor-promoting phorbol ester) and OAG (synthetic diacylglycerol), both potent activators of protein kinase C, imitate the action of EGF in rapidly elevating pHi and stimulating cell growth in thyroid cells. Trifluoperazine, an inhibitor of protein kinase C, inhibited EGF-, TPA-, and OAG stimulated cell alkalinization and growth. The data suggest that activation of protein kinase C may be involved in the mechanism of EGF-stimulated cell alkalinization and growth of the thyroid cells. PMID- 2316640 TI - Eicosanoid production in rabbit vascular tissues and placentas. AB - In pregnant rabbits, systemic levels of prostaglandin E2 (PGE2) are elevated. To evaluate the source of the rise in circulating levels of PGE2, eicosanoid production was determined in rabbit placental cotyledons and the following vascular tissues: mesenteric arteries, main renal arteries, and intrarenal preglomerular vessels (n = 6 or 7 rabbits). Comparisons were made with vascular tissues from nonpregnant rabbits (n = 6 or 7). Freshly isolated tissues were incubated for 15 min at 37 degrees C. Medium aliquots were analyzed for eicosanoids by radioimmunoassay. Maximal net production and release (pg/microgram protein) was determined by subtraction of the quantity of eicosanoids present in medium before incubation from that present at the end of incubation. Net production and release of 6-ketoprostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin, and of PGE2 was similar in vascular tissues from pregnant and nonpregnant rabbits. Thromboxane B2 (TxB2) generation in preglomerular vessels from pregnant rabbits was lower (P less than 0.05) than that of nonpregnant rabbits. This could contribute to renal vasodilation in pregnancy. The pattern of eicosanoid production in vascular tissues was 6-keto PGF1 alpha greater than PGE2 greater than TxB2, and in cotyledons it was PGE2 greater than 6-keto-PGF1 alpha greater than TxB2. In cotyledons, PGE2 and TxB2 production was 56-219 and 2-12 times that in maternal vascular tissues, respectively. These data suggest that physiologically significant quantities of eicosanoids may be released by rabbit placental tissue. PMID- 2316642 TI - Intracerebroventricular infusion of RU28318 blocks aldosterone-salt hypertension. AB - The chronic intracerebroventricular (icv) infusion of aldosterone in rats and dogs elevates the blood pressure within 10-14 days at doses far below those that produce hypertension systemically. The effect in rats is dose dependent and blocked by the concomitant icv infusion of the antimineralocorticoid, prorenone. The effect of the icv infusion of RU28318, another specific spironolactone mineralocorticoid antagonist, on the hypertension produced by chronic subcutaneous (sc) administration of aldosterone in sensitized rats was reported. Miniosmotic pumps were used to deliver 1 micrograms/h aldosterone sc and 1.1 micrograms/h RU8318 icv. Over a 24-day period the indirect systolic blood pressure of the control, RU28318 icv, and aldosterone sc plus RU28318 icv groups increased from 105 to 123 mmHg and were not significantly different from each other, whereas the aldosterone sc group increased to 156 mmHg. RU28318, icv or sc, did not alter the increase in urine volume produced by aldosterone sc, and there was no significant differences in weight between the groups. This study provides evidence of the importance of the central nervous system in the pathogenesis of hypertension produced by systemic mineralocorticoid excess. PMID- 2316643 TI - Free amino acids in muscle: effect of muscle fiber population and denervation. AB - One hindlimb of each rat was denervated by sectioning the sciatic nerve. Three days later, soleus, plantaris, and gastrocnemius muscles of the sham hindlimb and the contralateral denervated hindlimb were excised and analyzed for intracellular concentrations of 23 free amino acids and the dipeptides carnosine and anserine. Compared with the sham soleus (slow-twitch) muscle, the sham plantaris and gastrocnemius (fast-twitch) muscles showed 57-81% lower concentrations of histidine, glutamine, glutamate, aspartate, and serine and also 32-78% lower levels of taurine, citrulline, phosphoserine, and ornithine. On the other hand the fast-twitch muscles exhibited 31% higher concentrations of free glycine and alanine and 113-127% higher levels of carnosine and anserine than the soleus muscle. The denervation caused greater changes in soleus muscle than in the other two muscles. The denervation-induced changes in soleus muscle included 38-87% increases in concentrations of free valine, leucine, isoleucine, and glutamate associated with 21-56% decreases in the levels of glutamine, glycine, aspartate, serine, alanine, and citrulline. It is concluded that both muscle fiber population and muscle denervation have an independent effect on the intracellular concentrations of free amino acids in muscles. PMID- 2316644 TI - Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria. AB - Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. In this paper the potential coupling of mitochondrial metabolism to mitochondrial protein synthesis was investigated and the concentration of nucleotides and substrates for optimal translation in isolated rat heart mitochondria was determined. It was demonstrated that optimal isolated heart mitochondrial protein synthesis required the presence of an oxidizable substrate. Of the substrates tested, glutamate (20 mM) supported translation best followed by malate, succinate, and alpha-ketoglutarate, whereas pyruvate supported synthesis poorly. Unlike other recent mammalian mitochondrial systems, the presence of an oxidizable substrate was required for translation even in the presence of medium ATP and an exogenous energy-generating system. Mitochondrial translation also required the presence of adenine nucleotide that could be added as ADP or ATP; however, ATP added above 0.5 mM became progressively inhibitory. As a result, synthesis was supported significantly better by ATP synthesized by the system from added ADP, than by ATP added directly to the system. However, if the phosphorylation of ADP was prevented by limiting the phosphate concentration, ADP itself strongly inhibited mitochondrial protein synthesis. This inhibition appeared to be closely related to the energy charge of the system rather than to absolute levels of ADP, indicating for the first time that mitochondrial translation, like its cytoplasmic counterpart is regulated by energy charge. Last, this system did not require the inhibition of guanine nucleotide or exogenous energy-generating systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316645 TI - Pseudoketogenesis in hepatectomized dogs. AB - Overestimation of ketone body turnover in vivo, measured by tracer kinetics, could occur if specific activity or molar percent enrichment is diluted in extrahepatic tissues by label exchange via reversal of 3-oxoacid-CoA transferase, a process we call pseudoketogenesis. To test this hypothesis, euglycemic hepatectomized dogs were injected with a bolus of acetoacetate (0.8 mmol/kg), 32% enriched in [3,4-13C2]acetoacetate. Concentrations and labeling patterns of blood acetoacetate and R-3-hydroxybutyrate were measured by selected ion-monitoring gas chromatography-mass spectrometry. During the 60 min after bolus injection of [3,4 13C2]acetoacetate, the molar percent enrichment of blood [3,4-13C2]acetoacetate decreased to 73 +/- 3% (n = 5) in controls and to 11.5 +/- 0.8% (n = 3) during infusion of dichloroacetate, an activator of pyruvate dehydrogenase. The enrichment of R-3-hydroxy-[3,4-13C2]butyrate followed closely that of [3,4 13C2]acetoacetate. These dilutions occurred despite a net uptake of ketone bodies. Concomitantly, 10.6 +/- 2.2 (n = 5) and 6.0 +/- 2.9% (n = 3) of [13C]acetoacetate molecules were labeled on all four carbons in control and dichloroacetate-treated dogs, respectively. This uniformly labeled acetoacetate arises from partial equilibration between [3,4-13C2]acetoacetate and [1,2 13C2]acetyl-CoA via the reactions catalyzed by 3-oxoacid-CoA transferase and acetoacetyl-CoA thiolase. Our data demonstrate the reversibility of the 3-oxoacid CoA transferase in intact extrahepatic tissues and support the concept of pseudoketogenesis. This phenomenon has been quantitated by kinetic analysis of the data. PMID- 2316646 TI - Glucose is required to maintain ATP/ADP ratio of isolated bovine cerebral microvessels. AB - Isolated bovine cerebral microvessels (ICMV) were incubated with different metabolic fuels to determine the effect of each of them on microvessel energy state. With no fuel added to the medium, the ATP/ADP generally decreased from initial values of 1.5-3 down to 1-1.5 over 4 h; the ATP content also declined approximately 50%. In contrast, with glucose present, the ATP/ADP increased, and the ATP content was maintained. Pyruvate, beta-hydroxybutyrate, glutamate, and oleate were ineffective; oleate added together with carnitine gave some improvement but less than with glucose. Oxygen consumption by ICMV did not differ appreciably in fuel-free or glucose-containing medium. Addition of an inhibitor of fatty acid oxidation, 2-tetradecylglycidate, depressed the ATP/ADP. These results suggest that ICMV require glycolysis to maintain both their content of ATP and their ATP/ADP. They also suggest that endogenous lipid is an important fuel for isolated microvessels. PMID- 2316647 TI - Cold-restraint stress increases rat fecal pellet output and colonic transit. AB - Increased fecal pellet output that occurs during cold-restraint stress (CRS) was evaluated systematically. Free-feeding rats, which exhibit a reduced occurrence of gastric ulcers under these conditions, were studied. CRS significantly increased fecal pellet production and fluid content. However, the fecal output produced during CRS was not associated with increased gut secretory activity or somatic motor activity associated with cold restraint and did not occur in anesthetized animals. Cold and restraint stress were additive in producing increased fecal output. Significant dose-related decreases in fecal output were produced by drugs that decrease gut transit (i.e., B-HT 920, clonidine, Lomotil, loperamide, and lidamidine). Anticholinergic-antisecretory drugs, antidepressants, and tranquilizers had little effect on fecal output or fluid content. Changes in gastrointestinal transit did not contribute to the increased fecal output during CRS. Transit in the lower small intestine was not altered, but the cecum tended to empty more contents into the large intestine during CRS. Colonic transit was dramatically affected by CRS, which eliminated retrograde transit and produced the evacuation of the majority of colonic contents. The increased colonic transit produced by CRS was decreased in a dose-related fashion by hexamethonium, nifedipine, loperamide, and B-HT 920. In several time-response and drug-inhibition studies during CRS, both fecal pellet output and colonic transit were affected similarly. These data indicate that CRS appears to change central nervous system output to the colon and that it alters colonic smooth muscle motility in a manner that facilitates colonic transit and evacuation. Small intestinal transit is not involved in this phenomenon and is regulated differently during CRS. PMID- 2316648 TI - Mechanical properties of isolated human esophageal smooth muscle. AB - Isolated smooth muscle strips from the human esophagus representing both the longitudinal and circular layers of the esophagogastric junction and the esophageal body were prepared. The strips were mounted in organ baths, and resting length was defined. By repeatedly increasing the length of the strips with 20% of resting length and recording values of resting and active tensions, length-tension relations for each muscle type were constructed. Only circular strips from the esophagogastric junction developed active, resting tension, disclosed by replacing the normal Ca2(+)-containing Krebs solution with Ca2(+) free medium. Carbachol (10(-6) M) was used for submaximal activation of the contractile apparatus. At lengths between 180 and 260% of resting length, all strips reached optimum length (LO) where further elongation gave no further increase in active tension development. Repeated stimulations with carbachol was possible at a length of 200% of LO without affecting reproducibility. Determination of different collagen components revealed no differences between muscle types. PMID- 2316649 TI - Effects of transmural field stimulation in isolated muscle strips from human esophagus. AB - Smooth muscle strips representing longitudinal and circular muscle layers of the esophagogastric junction (EGJ) and esophageal body (EB) of the human esophagus were prepared. The strips were mounted in organ baths and isometric tension was recorded. Square wave stimulation was applied through platinum electrodes. Only responses abolished by tetrodotoxin (TTX) were considered neurogenic. Strips taken from longitudinal muscle layers of the EB and EGJ contracted during field stimulation. The responses evoked were abolished by atropine, and optimal frequency of stimulation was 40 Hz. In strips taken from the circular muscle layer of the EB, a contraction occurred after cessation of the stimulus. Atropine inhibited 90% of this response; the optimal stimulation frequency was 40 Hz. When a tone was induced in strips from this layer, a TTX-sensitive relaxation was seen during field stimulation. During stimulation of strips from the EGJ circular muscle layer, which was the only preparation developing spontaneous active tone, a relaxation was seen. A small contraction followed after termination of the stimulus. The relaxation, which was nonadrenergic, noncholinergic, reached maximum at 10 Hz. Atropine inhibited 40% of the contraction. The results suggest that in the longitudinal muscle layer of the human lower esophagus field stimulation causes postganglionic nerves to release transmitter(s) acting on muscarinic receptors. The responses of circular muscle layers seem to be mediated through release of at least two transmitters. PMID- 2316650 TI - Influence of morphine or capsaicin pretreatment on rat gastric microcirculatory response to PAF. AB - Capsaicin pretreatment, which destroys primary sensory afferent neurons, or morphine, which can inhibit peripheral sensory neurons, augments gastric damage induced by platelet-activating factor (PAF). The concurrent effects of such treatments on the changes in gastric mucosal blood flow (GMBF), as estimated by hydrogen gas clearance, and in systemic arterial blood pressure (BP) have now been determined in anesthetized rats. Intravenous infusion of PAF (25 and 50 ng.kg-1.min-1 for 30 min) induced dose-related histologically assessed mucosal damage, which was significantly potentiated by neonatal capsaicin pretreatment. Capsaicin pretreatment did not affect resting BP or GMBF or the fall in BP induced by PAF but did significantly potentiate the PAF-induced reduction in GMBF. Likewise, morphine (1.5 mg/kg iv) did not affect resting BP or GMBF or the fall in BP but did enhance the reduction in GMBF and potentiated the mucosal damage after PAF infusion; both of these effects were abolished by the opioid antagonist naloxone (1 mg/kg iv). These findings indicate that the deleterious gastric microcirculatory changes induced by PAF are enhanced by functional ablation of sensory afferent neurons and by morphine, which may act on these neurons; these effects may therefore underlie the potentiation of gastric damage. Such local sensory neurons thus appear to be involved in the regulation of local protective microvascular responses to noxious challenge. PMID- 2316651 TI - Splanchnic and systemic hemodynamics in mice using a radioactive microsphere technique. AB - Mice are commonly used for the study of human disease processes. However, techniques for measuring systemic and hepatic blood flow in mice have not been developed. We attempted the conventional technique of radiolabeled microsphere injection into the left ventricle, but difficulties were encountered, including unsuspected ventricular perforation and outflow obstruction in 68% of the animals. We therefore evaluated whether an injection into the carotid artery close to the aortic arch can fulfill the criteria (approximately or greater than 300 microspheres in femoral blood or tissues, adequate mixing of microspheres with blood, and no significant alteration of blood pressure during microsphere injection) required for accurate measurement of systemic and regional hemodynamics. Carotid artery injection resulted in adequate mixing and number of microspheres in tissues in 78 and 91% of the animals, respectively. Portal venous inflow was 1.8 +/- 0.3 ml.min-1.g liver tissue-1 and renal blood flow was 5.1 +/- 0.75 ml.min-1.g tissue-1. Compared per unit weight, these values are quite similar to those reported in rats. Cardiac output was 12.1 +/- 1.2 ml/min and cardiac index was 462 +/- 47 ml.min-1.kg body wt-1. The reliability of cardiac output determination is improved if whole body radioactivity is taken into account. Five of 22 animals had to be excluded because of either a low number of microspheres in tissues or inadequate mixing of microspheres with blood (shown by asymmetrical distribution of microspheres between left and right kidney). With modifications, the radioactive microsphere technique can be adapted to the hemodynamic study of mice. PMID- 2316652 TI - Jejunal adenosine increases during food-induced jejunal hyperemia. AB - If adenosine mediates postprandial intestinal hyperemia, increases in local adenosine release must accompany the hyperemia. We tested this by determining jejunal venous and arterial plasma adenosine concentrations, jejunal blood flow, and oxygen consumption before and during placement of normal saline or predigested food plus bile into the jejunal lumen of anesthetized dogs. Adenosine concentrations were measured by high-pressure liquid chromatography. Luminal placement of food significantly increased blood flow (+46%), oxygen consumption (+40%), venous adenosine concentration (+56 nM), and adenosine release (+1.7 nmol.min-1.100 g tissue-1) during the initial 3 min of placement. Whereas blood flow and oxygen consumption remained elevated for the entire 15-min placement period, venous adenosine concentration and release returned to control levels at 7 and 11 min after placement, respectively. Placement of the same volume of normal saline did not significantly alter any variables measured, indicating that the food-induced changes were because of constituents of food. In conclusion, introduction of predigested food into the jejunal lumen significantly increases adenosine releases into the local venous blood during the initial several minutes of food placement. The increased adenosine production and release may play a role in postprandial jejunal hyperemia. PMID- 2316653 TI - Mechanical aspects of rabbit fecal dehydration. AB - The hydrostatic pressure required to reduce the water content of rabbit feces in an odometer from greater than 80 to less than 65% was approximately 5 atm. This pressure was unaffected by raising the temperature from 20 to 37 degrees C. It became progressively more difficult to dehydrate feces as consolidation occurred, as is evident from the significant (P less than 0.001) reduction in the fecal consolidation coefficient (Co) from 1.76 +/- 0.25 X 10(-6) (n = 4) to 1.35 +/- 0.093 X 10(-7) m2/s (n = 4) and the fecal fluid permeability coefficient (k) from 4.10 +/- 0.51 X 10(-8) (n = 4) to 1.42 +/- 0.12 X 10(-10) m/s (n = 4), concomitant with the reduction in fecal water content. The results suggest that rabbit hard feces are unlikely to be produced, under physiological conditions, by mechanical pressure exerted by the wall of the colon or by a prolonged retention time of hard feces by the distal colon. The hypertonic absorbate (1,000 mosmol/kg) produced by rabbit descending colon is of sufficient magnitude to overcome the fecal resistance to dehydration. PMID- 2316655 TI - Acute and chronic ethanol on hepatic oxygen ethanol and lactate metabolism in cats. AB - The effects of increasing blood ethanol levels on hepatic hemodynamics and O2, ethanol, and lactate metabolism were studied in two groups of anesthetized cats: a control group and a group whose prior fluid intake contained 2, 4, then 8% ethanol for 24 days. Within each group, responses were compared in cats with acutely denervated and innervated livers. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to allow hemodynamic measurements and repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cats' blood volume. Vmax for ethanol was 105 +/- 9 and 91 +/- 6 mumol.min 1 g liver-1 and Km was 136 +/- 18 and 168 +/- 24 microM for control and chronic alcohol groups, respectively. There was no stimulation of ethanol metabolism after chronic administration. O2 uptake by the liver was not altered during acute ethanol administration in any group and base-line O2 uptakes before acute administration of ethanol were not different between normal and chronic ethanol groups. No evidence for a hypermetabolic state induced by chronic ethanol administration was seen in innervated or acutely denervated livers. Oxidation of ethanol required 40-45% of normal O2 uptake; thus other oxidative processes must have been suppressed during ethanol metabolism. Hepatic lactate uptake remained unaltered when ethanol metabolism was less than 0.5 Vmax, but was suppressed on an equimolar basis with ethanol metabolism when ethanol metabolism rose to greater than 0.5 Vmax. Thus lactate metabolism is one process that can be suppressed to allow ethanol metabolism without additional O2 uptake by the liver. PMID- 2316654 TI - Regional cholinergic differences between distal and proximal colonic myenteric plexus. AB - We investigated differences in myogenic and neural response of proximal vs. distal guinea pig colon in longitudinal and circular muscle. Spontaneous phasic contractions were more intense in distal colon in both layers. Phasic contractile frequency was also greater in distal colon in both layers. In both longitudinal and circular muscle, acetylcholine induced greater contractions in distal than in proximal colon (maximal response: longitudinal, 7.00 +/- 1.04 X 10(4) vs. 3.50 +/ 0.49 X 10(4) N/m2; circular, 3.29 +/- 0.82 X 10(4) vs. 8.92 +/- 1.30 X 10(3) N/m2). Compared with proximal colon, electric field stimulation induced greater atropine-sensitive contractions in distal colon in both muscle layers (maximal response: longitudinal, 4.22 +/- 0.53 X 10(4) vs. 7.53 +/- 1.97 X 10(3) N/m2; circular, 2.14 +/- 0.79 X 10(3) vs. -5.28 +/- 2.04 X 10(2) N/m2). In contrast, there were no regional differences in atropine-insensitive relaxations. Veratridine (10(-5) M) stimulated greater [3H]acetylcholine release from distal longitudinal muscle-myenteric plexus than from proximal preparations (11.44 +/- 2.03 vs. 5.84 +/- 1.26% of total tissue radioactivity). These data suggest the greater contractile responses in the distal colon are because of enhanced cholinergic response to neural stimuli and increased muscle sensitivity to acetylcholine, whereas there are no differences in the inhibitory responses to neural stimuli. PMID- 2316656 TI - Exocrine secretion and processing of pro-xenopsin in rat gastric lumen. AB - This study examines the effects of acid, acid secretagogues, and pepstatin on gastric luminal concentrations of xenopsin-like immunoreactivity (XPLI) by in situ luminal perfusion of the stomach in anesthetized rats. During perfusion with saline over a 2-h period, the concentration of XPLI fell in parallel with acid output. Levels of XPLI fell more rapidly when the saline contained 20 micrograms/ml pepstatin A and when phosphate-buffered saline (pH 7.0) was used. These treatments did not, however, alter acid output. After a basal condition was established at 90 min, intravenous injection of carbachol, pentagastrin, or histamine stimulated acid and pepsin secretion and also led to an increase in XPLI concentration, which was pepstatin sensitive. Acid itself was also a stimulus for pepsin and XPLI output, which were correlated at various levels of acidity. Although pepstatin blocked the effect of acid on XPLI output, it did not lead to an accumulation of xenopsin (XP) precursor in the luminal fluid. However, the decrement in acid-stimulated XPLI output seen in the presence of pepstatin was matched by an increment in XP precursor associated with the mucosal surface. During high-pressure liquid chromatography, approximately 70% of the acid generated XPLI eluted at the position of mammalian XP. These data support the notion that, during heightened acid output, XP is secreted by a pepsin-dependent process or generated by the action of pepsin on XP precursor present on the mucosal surface of the rat stomach. PMID- 2316657 TI - Effect of histamine and 1,4-methylhistamine on gastric vascular resistance in dogs. AB - The goal of this study was to compare the relative potency of histamine and its metabolite, 1,4-methylhistamine, as vasodilators of the gastric circulation. Changes in vascular resistance were measured during local intra-arterial infusion of graded doses of histamine and 1,4-methylhistamine to an ex vivo segment of dog stomach. Infusate concentrations were adjusted to deliver calculated arterial blood concentrations of 0, 3.7, 11, 33, 100, 300, and 900 ng/ml of each substance to the stomach segment. We found that histamine caused rapid dose-related decreases in gastric vascular resistance of up to -47.6 +/- 1.3% compared with control values. The effects of histamine were reversible when infusions ended. In contrast, there were no statistically significant changes in vascular resistance at any dose of 1,4-methylhistamine. In addition, modifications to previous methods using histamine antagonists resulted in greater attenuation of histamine induced gastric vasodilation. Our results support a role for locally released histamine, but not for 1,4-methylhistamine, as a mediator of gastric vasodilation. PMID- 2316658 TI - Postnatal development of colonic electrolyte transport in rabbits. AB - Postnatal changes in adrenal gluco- and mineralocorticoid secretion and colonic sodium and chloride transport were examined. New Zealand White rabbits, age 10 14, 18-22, and 25-30 days, and adult animals (6-10 wk) were studied. Serum cortisol, corticosterone, aldosterone, and mucosal Na(+)-K(+)-ATPase activities were measured in each age group. Transport studies were performed in vitro under short-circuited conditions in distal colon at all age groups and in proximal colon in days 10-14 and 18-22 and in adult animals. Serum glucocorticoids varied little until after day 30 when they rose to adult levels. On the other hand, serum aldosterone levels were two- to threefold higher in days 10-14 and 18-22 animals but fell to adult levels by day 25. In distal colon, amiloride inhibitable electrogenic Na+ absorption was present at all ages but was significantly greater (P less than 0.01) in days 10-14 (3.8 +/- 0.5 mu eq.cm-2.h 1) and 18-22 (4.2 +/- 0.4) rabbits compared with adults (1.9 +/- 0.4) but not day 25-30 (2.8 +/- 0.5). In proximal colon, Na+ absorption was significantly higher (P less than 0.05) in day 10-14 (1.6 +/- 0.5 mu eq.cm-2.h-1) compared with day 18 22 (-0.2 +/- 0.5) and adults (0.06 +/- 0.5) and was amiloride insensitive. Neither chloride transport nor mucosal Na(+)-K(+)-ATPase demonstrated significant age-related changes in either region of colon. These results indicate that both proximal and distal colonic Na+ transport undergoes postnatal changes. In distal but not proximal colon these changes appear to be regulated by circulating aldosterone probably by increasing apical membrane permeability to Na+. PMID- 2316659 TI - Electrical and mechanical interactions between the muscle layers of canine proximal colon. AB - Electrical and mechanical interactions between the two smooth muscle layers of canine colon have been studied using a dual sucrose gap apparatus. Muscle samples were dissected into an L-shape, with one leg cut in the circular direction and the other cut in the longitudinal direction. Longitudinal muscle was removed from the circular leg and circular muscle was removed from the longitudinal leg. The bend of the L contained both layers. The activity of the two layers was studied simultaneously under basal conditions, after stimulation by neostigmine and carbachol, and in the presence of tetrodotoxin. Interactions were more common after stimulation and were marked by modification of one layer's mechanical and electrical activity during increased activity in the other layer. Two patterns were commonly observed. First, during a burst of membrane potential oscillations and spike potentials in the longitudinal layer, slow waves in the circular layer developed spike potentials and some slow waves were also prolonged. Second, during a slow-wave cycle in the circular layer, the amplitude of membrane potential oscillations in the longitudinal layer was increased with an associated increase in the incidence of spike potentials. These interactions were associated with contractions of increased strength, which were similar in both layers. All interactions continued after nerve-conduction blockade by tetrodotoxin. PMID- 2316660 TI - Feedback responses during sequential inhibition of angiotensin and thromboxane. AB - Since thromboxane (Tx) can mediate the actions of angiotensin II (ANG II), we investigated interaction between these systems on the tubuloglomerular feedback (TGF) response. TGF was assessed from proximal stop-flow pressure (PSF) during orthograde perfusion of the loop of Henle (LH) between 0 and 40 nl/min. In the basal state, TGF was 11.3 +/- 0.8 mmHg. In series 1 experiments, it was unaltered by vehicle (+0.3 +/- 0.9 mmHg, n = 9, NS), was reduced by an ANG II antagonist, saralasin (-2.4 +/- 1.1 mmHg, n = 8, P less than 0.0005), and by a TxA2 antagonist SQ 29,548 (-4.8 +/- 0.6 mmHg, n = 11, P less than 0.0001). Both drugs together produced an additive blunting of TGF of -6.9 +/- 0.7 mmHg. In series 2 experiments, TGF was again unchanged by vehicle (+0.2 +/- 0.6 mmHg). It was reduced by -4.4 +/- 0.2 mmHg (P less than 0.0001) by an angiotensin-converting enzyme inhibitor CGS-14,824A (50 mg/kg, n = 5) and by -4.0 +/- 0.4 mmHg (P less than 0.001) by a Tx synthesis inhibitor CGS-13,080 (50 mg/kg, n = 7). Although both drugs together produced a further blunting of the response of -6.1 +/- 0.4 mmHg, this was significantly (P less than 0.001) less than additive. In both series, a response (averaging 3.5 +/- 0.3 mmHg) persisted in all rats given combined antagonists or inhibitors. In conclusion, both ANG II and TxA2 can modulate TGF-induced changes in PSF independently, and the response probably requires other system(s) in addition to ANG II and TxA2. PMID- 2316661 TI - Single-nephron adaptations to partial renal ablation in the dog. AB - Micropuncture and histological studies were performed in dogs to characterize single-nephron adaptations to partial renal ablation. Dogs underwent sham surgery (group 1, n = 6), three-fourths nephrectomy (group 2, n = 10), or seven-eighths nephrectomy (group 3, n = 6). Single-nephron glomerular filtration rate (SNGFR) was 71.0 +/- 4.2 nl/min in group 1, 132.5 +/- 9.6 nl/min in group 2, and 161.8 +/ 12.4 nl/min in group 3 (P less than 0.05). There were parallel increases in single-nephron glomerular plasma flow rate (GPF), with a mean value of 235.3 +/- 20.1 nl/min in group 1, 442.4 +/- 34.4 nl/min in group 2, and 569.6 +/- 73.7 nl/min in group 3 (P less than 0.05, group 1 vs. groups 2 and 3). Glomerular capillary pressure, estimated from the sum of proximal tubule stop-flow pressure and arterial oncotic pressure, was 63.2 +/- 1.9 mmHg in group 1, 73.5 +/- 2.0 mmHg in group 2, and 77.9 +/- 2.2 mmHg in group 3 (P less than 0.05, group 1 vs. groups 2 and 3). The mean glomerular transcapillary hydraulic pressure gradient (delta P) in group 2 was not different from group 1 (46.8 +/- 1.3 vs. 43.9 +/- 1.8 mmHg, NS); however, it was significantly increased in group 3 (50.0 +/- 1.4 mmHg; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316662 TI - Amino acid transport: microinfusion and micropuncture of Henle's loops and vasa recta. AB - Amino acids appear to be reabsorbed distal to the tips of loops of Henle and may be recycled between loops and vasa recta in rat papilla. These possibilities were examined further by microinfusion and micropuncture of loops of Henle and vasa recta. To obtain information on the specificity of amino acid transport distal to the tips of the loops, ascending limbs were continuously microinfused with radioactively labeled L- and D-alanine, L-glutamate, taurine, and mannitol. About 30% of the L- and D-alanine and L-glutamate but none of the taurine or mannitol appeared to be reabsorbed. These results suggest that an acidic and a neutral amino acid are reabsorbed to a similar extent, that reabsorption is not stereospecific, but that it does not occur indiscriminately for all amino acids or for all molecules of similar size. Continuous microinfusion of ascending vasa recta with radioactively labeled L- and D-alanine suggests that amino acids may be able to move from vasa recta into tubules (apparently loops of Henle) without first entering the systemic circulation. However, micropuncture measurements of concentrations of endogenous amino acids in thin ascending limbs and adjacent descending vasa recta do not demonstrate a gradient for passive movement out of loops. PMID- 2316663 TI - Effects of apical membrane Cl(-)-formate exchange on cell volume in rabbit proximal tubule. AB - We used real-time recordings of cell volume changes to test for the role of the Cl(-)-formate exchanger in mediating NaCl entry across the apical membrane of rabbit proximal tubule cells. In the absence of extracellular Cl-, 0.5 and 5 mM formate in the tubule lumen induced an increase in cell volume of 1 and 9%, respectively. Formate-induced cell swelling was reduced by alkalinizing the tubule lumen or by addition of luminal amiloride (2 mM), indicating that the increase in cell volume results from the intracellular accumulation of Na-formate via nonionic diffusion of formic acid in parallel with Na(+)-H+ exchange. The cell volume increase induced by 0.5 mM formate was potentiated (from 1 to 4%) by Cl-, as expected for a formate-mediated stimulation of NaCl uptake via parallel Cl(-)-formate exchange and Na(+)-H+ exchange across the apical membrane. By contrast, the cell volume increase induced by 5 mM formate was attenuated (from 9 to 4%) by Cl-. The attenuating effect of Cl- on formate-induced cell swelling required the operation of the apical membrane Cl(-)-formate exchanger. The effect of 1:1 Cl(-)-formate exchange to attenuate formate-induced cell swelling can be explained if the cell possesses a volume-activated anion exit pathway, most likely at the basolateral cell membrane, that is capable of mediating the efflux of Cl- but not formate from the cell. PMID- 2316664 TI - Tubuloglomerular feedback responses during peritubular infusions of calcium channel blockers. AB - Experiments were performed in pentobarbital-anesthetized rats to evaluate the dependence of the effector limb of the tubuloglomerular feedback mechanism on transmembrane calcium flux through potential-operated calcium channels. Peritubular capillary infusions of the calcium channel blockers, verapamil and nifedipine, were used to achieve high intrarenal levels without influencing arterial blood pressure. Proximal tubule stop-flow pressure (SFP) and single nephron glomerular filtration rate (SNGFR) tubuloglomerular feedback responses were obtained during control conditions and during simultaneous peritubular capillary infusion with an isotonic saline solution containing either verapamil or nifedipine. Infusion of either 10(-3) M verapamil or 10(-3) M nifedipine, at a rate of 20 nl/min, increased resting SFP (measured during conditions of zero distal volume delivery) and markedly attenuated both the SFP and SNGFR feedback responses to a late proximal perfusion rate of 30 nl/min. Infusion of verapamil (10(-3) M) also increased the slope of the relationship between SFP and renal arterial perfusion pressure between 80 and 120 mmHg (0.43 +/- 0.03 vs 0.24 +/- 0.02, P less than 0.001, n = 10). These findings support the hypothesis that the preglomerular contractile elements responsive to signals from the macula densa cells are activated by calcium influx through potential-operated calcium channels. Furthermore, the preglomerular contractile elements sensitive to calcium channel blockers can dilate further even when orthograde flow to a single macula densa segment is interrupted. PMID- 2316665 TI - Whole-cell currents in rat cortical collecting tubule: low-Na diet increases amiloride-sensitive conductance. AB - Individual principal cells within the rat cortical collecting tubule were studied under voltage-clamp conditions using the whole-cell variation of the patch-clamp technique. Isolated tubules were split to expose the apical membrane surface and bathed in NaCl medium at 23 degrees C. When carboxyfluorescein was included in the patch pipette, the dye diffused rapidly into the cell being clamped but did not spread to neighboring cells, indicating a lack of cell-to-cell coupling. Average cell capacitance under whole-cell clamp conditions with KCl in the pipette was 18 +/- 2 pF (n = 10 cells) in rats maintained on a normal diet, consistent with that expected from morphometric measurements of cell surface area. The capacitance increased to 36 +/- 7 pF (n = 8 cells) for rats kept on a low-Na diet, indicating that cell membrane area was increased under these conditions. The amiloride-sensitive whole-cell conductance (GNa), assumed to equal the conductance through apical Na channels, was determined as the slope of the current-voltage relation near zero holding potential. GNa was 6.0 +/- 1.7 nS/cell (n = 12) for rats maintained on a low-Na diet compared with 0.06 +/- 0.08 nS/cell (n = 13) for rats kept on a normal diet. The amiloride-insensitive whole cell conductance averaged 9.1 +/- 2.0 nS/cell, with no significant difference between low-Na and normal groups. Sodium channel density (N) was estimated from GNa, the mean open probability of the channel, and the single-channel conductance. N equals 3,000 channels/cells in rats on a low-Na diet compared with N less than 100 channels/cell for rats on a normal diet. PMID- 2316666 TI - Ca2(+)-dependent inhibition of sodium transport in rabbit cortical collecting tubules. AB - Experiments were carried out to test whether maneuvers believed to increase intracellular Ca2+ concentration [( Ca2+]cell) inhibit Na transport in cortical collecting tubules (CCTs). Unidirectional Na efflux (JNa1----b) and Na influx (JNab----1) were measured isotopically in isolated perfused renal CCTs of rabbits. The animals were either untreated or pretreated with deoxycorticosterone (DOC) for 1-3 wk. To raise [Ca2+]cell, ionomycin or quinidine were added to, or [Na] reduced in, pertubular fluid. In control DOC-pretreated CCTs JNa1----b tended to saturate as luminal Na concentration was increased, reaching 22.9 +/- 1.2 pmol.cm-1.s-1 at 145 mM. In addition, in these CCTs, in contrast to non-DOC treated tubules, the apical cell membrane was not found to be rate limiting for Na reabsorption as neither amphotericin B nor vasopressin further enhanced JNa1-- -b. In non-DOC-treated CCTs 10(-6) M ionomycin inhibited JNa1----b by 44.7%. When DOC-pretreated CCTs were exposed to either 10(-6)M ionomycin or 10(-4)M quinidine, JNa1----b was inhibited by 27 and 26%, respectively, while JNab----1 remained unchanged. This ionomycin-induced inhibition was Ca dependent. Exposure of DOC-pretreated CCTs to 5 mM Na-Ringer solution (Na replaced by choline or N methyl-D-glucamine) for 30 min reduced JNa1----b by 18-30%. The inhibition of JNa1----b caused by any of the three maneuvers was fully reversed upon addition of amphotericin B to the luminal fluid. The results are consistent with the view that a sustained increase in [Ca2+]cell reduces Na transport by inhibition of the rate of Na+ entry across the apical cell membrane. PMID- 2316668 TI - MPP+ is transported by the TEA(+)-H+ exchanger of renal brush-border membrane vesicles. AB - Rabbit renal brush-border membrane vesicles (BBMV) were used to study the transport of the cationic neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). An outwardly directed H(+)-gradient stimulated MPP+ uptake and led to the development of an active accumulation of MPP+ within the vesicles. H(+)-gradient driven MPP+ transport was saturable, with a maximal transport rate of 3 nmol.mg 1.min-1 and an apparent Michaelis constant (Kt) of 8 microM. MPP+ and tetraethylammonium (TEA) behaved as competitive inhibitors of one another's transport in renal BBMV, suggesting the presence of a common transport pathway for these organic cations. At an ambient pH of 7.5, preloading BBMV with MPP+ failed to stimulate TEA uptake, although trans TEA did stimulate MPP+ uptake. Increasing ambient pH to 8.5 (i.e., reducing competition between H+ and these organic cations for a common transport pathway) led to a clear reciprocal trans stimulation of TEA and MPP+ fluxes. With an equilibrium-shift protocol, a trans concentration of MPP+ energized uphill transport of TEA. We conclude that MPP+ and TEA share a common organic cation-H+ exchange pathway in the renal brush border, although turnover of an MPP(+)-loaded exchanger is slow compared with that for a TEA or H(+)-loaded exchanger. PMID- 2316667 TI - Mechanism of aluminum-induced calcium efflux from cultured neonatal mouse calvariae. AB - Aluminum has been shown to increase unidirectional 45Ca efflux from prelabeled bones in vitro; whether aluminum affects net calcium efflux and, if so, by what mechanism has not been studied. To examine the effects of aluminum on net calcium flux from bone we cultured live and dead neonatal mouse calvariae with and without graded concentrations of aluminum (10(-8) to 10(-5) M). Aluminum induced a dose-dependent net calcium efflux from live bone after 24 h, but not 3 h, which was similar in magnitude to that produced by 10(-8) M parathyroid hormone. The normal calcium influx into dead bone was not altered by aluminum. Release of beta glucuronidase, a lysosomal enzyme released by osteoclasts, increased after a 24-h incubation in aluminum-containing medium and was correlated with net calcium efflux. Calcitonin, an inhibitor of osteoclastic bone mineral dissolution, abolished the increase in beta-glucuronidase release and nullified the aluminum induced net calcium efflux. Thus aluminum induces cell-mediated net calcium efflux from bone and increases beta-glucuronidase release. Calcitonin inhibits the increase in both calcium efflux and beta-glucuronidase release, suggesting that aluminum stimulates osteoclasts to release bone mineral. PMID- 2316669 TI - Glomerulotubular balance in a mathematical model of the proximal nephron. AB - A nonelectrolyte model of proximal tubule epithelium has been extended by the inclusion of a compliant tight junction. Here "compliance" signifies that both the junctional salt and water permeability increase and the salt reflection coefficient decreases in response to small pressure differences from lateral interspace to tubule lumen. In previous models of rat proximal tubule, there has been virtually no sensitivity of isotonic salt transport to changes in peritubular oncotic force. With the inclusion of junctional compliance, decreases in peritubular protein can open the junction and produce a secretory salt flux. Thus the model can represent the "backflux hypothesis," as it was originally put forth (J. E. Lewy and E. E. Windhager, Am. J. Physiol. 214: 943-954, 1968). Additional calculations, simulating a tight junction with negligible water permeability, reveal that the quantitative impact of peritubular protein can be realized whether or not there is substantial junctional water flux. The epithelial model of proximal tubule has also been incorporated into a model of the proximal nephron, complete with glomerulus, peritubular capillary, and interstitium. The interstitial compartment is well mixed and interstitial pressure and osmolality are determined iteratively to achieve balance between tubule reabsorption and capillary uptake. For this model, two domains of operation are identified. When interstitial pressures are low, junctions are closed, and filtration fraction has no effect on proximal reabsorption. When interstitial pressures are relatively elevated, epithelial junctions are open, and proximal salt reabsorption changes in proportion to changes in filtration fraction. In neither domain, however, does the model tubule augment salt flux with isolated increases in luminal flow rate (at constant filtration fraction). The absence of a separate effect of tubule fluid flow on salt transport precludes perfect glomerulotubular balance. PMID- 2316670 TI - Autoregulation and tubuloglomerular feedback in juxtamedullary glomerular arterioles. AB - Videometric measurements of changes in vessel lumen diameters were made to investigate autoregulatory and tubuloglomerular feedback (TGF) responses of early efferent arterioles (EA), mid-to-late afferent arterioles (MAA), and terminal, juxtaglomerular afferent arterioles (JAA) in rat juxtamedullary nephrons in vitro. High-contrast shadow-cast images of blood-perfused arterioles at the glomerular vascular pole were obtained with incident illumination and long working-distance objectives fitted to a compound microscope. In response to an increase in blood perfusion pressure from 60 to 140 mmHg, strong autoregulatory vasoconstriction was observed in the MAA and JAA, with respective reductions in mean luminal diameter of 23 +/- 4 and 40 +/- 4% (mean +/- SE); EA diameter was unchanged. In response to TGF excitation by direct microinjection of Ringer solution into the cortical thick ascending limb segment near the macula densa, JAA luminal diameter decreased by 34 +/- 5%. The TGF responses were completely inhibited by the addition of 0.1 mM furosemide to the tubular injectate. Calcium channel blockade achieved by adding 1 microM nimodipine to the superfusate had no effect on early EA diameter but produced a blood pressure-dependent JAA and MAA vasodilation and complete inhibition of autoregulatory responses. These results provide direct evidence that the distal afferent arteriole in juxtamedullary nephrons is a major effector site for both renal autoregulation and tubuloglomerular feedback. PMID- 2316671 TI - Impaired renal response to a meat meal in insulin-dependent diabetes: role of glucagon and prostaglandins. AB - The renal response to 100 g/1.73 m2 protein load in the form of a meat meal was studied in 19 normal subjects and 35 normoalbuminuric insulin-dependent diabetic patients (IDDs) under conditions of sustained euglycemia. The area under the glomerular filtration rate (GFR) curve rose above base line by 1,904 +/- 292 in normals and 502 +/- 237 ml/1.73 m2 in IDDs (P less than 0.01). The meat meal induced a greater increment in the area under the glucagon curve in normals (14,930 +/- 186 pg.ml-1.min-1) than in IDDs (7,227 +/- 67, P less than 0.01); similarly urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha rose by 119 and 98%, respectively, in normals but only by 2% (P less than 0.01 vs. normals) and 10% (P less than 0.01 vs. normals) in IDDs. The fractional albumin clearance rose by 102 and 251% in normals and IDDs, respectively. In five normal subjects indomethacin administration abolished the GFR, glucagon, prostaglandin, and albuminuric response to meat ingestion. Glucagon replacement under indomethacin treatment failed to restore these responses. In five diabetic patients, selected for having a flat glucagon and GFR response to a meat meal, replacement of glucagon to postprandial levels increased urinary vasodilatory prostaglandins and restored a normal GFR response. Thus in normal subjects renal vasodilatory prostaglandins appear to be the final effector of the renal hemodynamic and albuminuric response to a meat meal. The prostaglandin increase is likely to be mediated under physiological conditions by a glucagon rise, which, however, has no effect per se on renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316672 TI - A theoretical approach to analyze pressure equilibria in the interstitium. AB - Inherent problems concerning the interstitial fluid pressure (IFP) are reinvestigated on theoretical grounds. Analyzing the thermodynamic and mechanical equilibria in the interstitium, it is concluded that IFP includes a pressure term originating from the elastic forces and an osmotic pressure term. A quantitative relationship is established between the IFP and all of the parameters responsible for the changes in the recorded pressure. The theoretical results suggest that, under control conditions, 1) there are no permanently existing free fluid spaces, 2) the gel pressure is atmospheric, and 3) the fluid equilibration techniques measure an osmotic pressure difference between the gel phase and the fluid phase created artificially by any of the pressure measuring devices. The pressure response during acute volume changes is attributed to the changes in the osmotic pressure term, gel volume, and elasticity. Volume and elasticity changes are reflected in the recorded IFP as promptly developing and permanent effects; on the other hand, osmotic processes result in slowly developing and transient effects. The volume-pressure relationship is also analyzed. PMID- 2316673 TI - Role of xanthine oxidase in ischemia/reperfusion injury. AB - Oxygen metabolites formed during reperfusion of ischemic kidneys prevent recovery of renal function after short periods of renal ischemia. Xanthine oxidase has been proposed as a source of toxic oxygen metabolites during reperfusion of ischemic kidneys. To determine whether the enzyme is converted from the non oxygen metabolite-producing dehydrogenase (type D) to the oxygen metabolite producing oxidase (type O), we measured type D and type O (total, reversible, and irreversible) xanthine oxidase in renal cortical homogenates after 30 min of ischemia in vivo and 60 min of reperfusion by the isolated perfused kidney technique. Total enzyme activity (type D plus type O) was not altered by ischemia or reperfusion. Compared with nonischemic conditions, ischemia increased total type O (53 +/- 5 vs. 21 +/- 3%, P less than 0.01) and reversible type O (15.4 +/- 1.5 vs. 2.1 +/- 1.4 U/g) xanthine oxidase activities. Reperfusion further increased total type O (82 +/- 3%) and reversible type O (27.7 +/- 3.3 U/g, both P less than 0.01 vs. nonischemic perfusions) xanthine oxidase activities. To determine the physiological role of xanthine oxidase in renal ischemia, we depleted rats of xanthine oxidase by feeding tungsten. After 4 wk of tungsten, renal xanthine oxidase levels were reduced by greater than 90% and renal function was markedly improved during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316674 TI - Glomerular effects of angiotensin II require intrarenal factors. AB - Glomerular ultrafiltration coefficient (Kf) of glomeruli isolated from kidneys of normovolemic rats decreases following infusion of angiotensin II (ANG II). Kf from isolated glomeruli after ANG II infusion in vivo and from isolated perfused kidneys following infusion of ANG II in vitro was measured to determine whether the decrease required the presence of systemic factors. Filtration was induced in vitro and the maximum rate of change in glomerular volume was used to calculate Kf. Glomerular capillary hydraulic conductivity (Lp) was calculated from Lp = Kf/A where the basement membrane area A was calculated as 3 X pi X D2. ANG II infusion in vivo in rats diminished Lp from 3.19 +/- 0.19 to 1.96 +/- 0.13 and to 1.82 +/- 0.11 microliters.min-1.mmHg-1.cm-2, respectively. ANG II infusion into isolated kidneys caused a similar decrease in Lp (3.55 +/- 0.11 to 2.37 +/- 0.07). ANG II infusion either in vivo or during isolated kidney perfusion decreases Kf and Lp. ANG II effects do not require the presence of extrarenal factors but depend on perfusion in situ since incubation of isolated glomeruli with ANG II did not alter Kf. PMID- 2316676 TI - Adenosine formation and energy metabolism: a 31P-NMR study in isolated rat heart. AB - Temporal and quantitative relations between cytosolic energy metabolism, adenosine efflux, and coronary flow were examined during 10 min of isoproterenol (ISO) infusion (60 nM) or hypoxia (5% O2) in isolated isovolumic rat heart. Myocardial metabolism was monitored using 31P-nuclear magnetic resonance spectroscopy, and venous effluent was collected and assayed for adenosine. During ISO infusion, coronary flow increased to approximately 170%, and [ATP]/[ADP] [Pi] (cytosolic phosphorylation potential) declined to less than 25% of preinfusion levels, respectively (P less than 0.001). During hypoxia, coronary flow increased to 190%, and [ATP]/[ADP] [Pi] declined to less than 25% of normoxic levels (P less than 0.001). Release of adenosine into the coronary venous effluent increased greater than 10-fold and displayed significant inverse linear correlations with log[ATP]/[ADP] [Pi] and positive linear correlations with free cytosolic [AMP] and coronary flow during ISO infusion and hypoxia. Adenosine deaminase (ADA) treatment reduced coronary vasodilation by approximately 30% during ISO infusion and 40% during hypoxia (P less than 0.001) and augmented chronotropic and inotropic responses to ISO infusion (P less than 0.01). Infusion of ADA potentiated changes in [ATP]/[ADP] [Pi] and [AMP] observed during ISO infusion and hypoxia (P less than 0.05). These results indicate that 1) endogenous adenosine mediates metabolic vasodilation in the heart, 2) adenosine modulates the response of isolated myocardium to catecholamines, 3) myocardial adenosine formation appears to be linked to cytosolic metabolism via changes in [ATP]/[ADP] [Pi] and [AMP], and 4) endogenous adenosine provides a significant, metabolically beneficial action in isolated hearts during hypoxia and inotropic stimulation. PMID- 2316675 TI - The 11 beta-OHSD inhibitor, carbenoxolone, enhances Na retention by aldosterone and 11-deoxycorticosterone. AB - Carbenoxolone sodium, CS, a liquorice derivative associated with hypertension and sodium retention, has been demonstrated to inhibit 11 beta-hydroxysteroid dehydrogenase, an enzyme that metabolizes cortisol and corticosterone to their respective inactive 11-dehydro products (cortisone and 11-dehydrocorticosterone). It has been proposed that the increased bioavailability of unmetabolized corticosterone and cortisol following 11 beta-OHSD inhibition allows these steroids to act on renal mineralocorticoid receptors to elicit the mineralocorticoid action. Here we describe how CS amplifies the antinatriuretic activity of aldosterone and deoxycorticosterone; the latter steroid is of particular importance in that it does not possess a hydroxyl group at the C-11 position in the steroid ring, indicating that another mechanism(s) in addition to 11 beta-OHSD inhibition is responsible for the amplification of the action of deoxycorticosterone. PMID- 2316677 TI - Sepsis-induced diastolic dysfunction in chronic canine peritonitis. AB - A chronic canine model of hyperdynamic sepsis was achieved by cecal ligation and puncture (SEP) in conjunction with continuous high-volume fluid resuscitation. Cardiac function was evaluated using ultrasonic cardiac crystals placed across the major, minor, and wall thickness axes of the left ventricle, together with simultaneous arterial and ventricular pressure measurement. Seven to 10 days after crystal implantation, animals were randomized to either SEP (n = 10) or sham laparotomy control (n = 7). SEP dogs became febrile and lethargic, with elevated leukocyte counts and positive blood cultures for enteric organisms. They were also hyperdynamic, with significant increases in heart rate and cardiac output and a fall in systemic vascular resistance. Systolic blood pressure, stroke volume, and ejection fraction remained stable. Relative to control, the SEP group demonstrated a significant reduction in intrinsic contractility during systole, as measured by the heart rate and load-independent index of left ventricular performance Emax (P less than 0.01), confirming the observations of others. In addition, however, diastolic function also became markedly abnormal with a progressive increase in unstressed and end-diastolic ventricular volumes (P less than 0.05) and a significant decrease in myocardial compliance as quantitated by transmural pressure vs. volume-strain analysis. It is hypothesized that this increase in diastolic volume helps to maintain global cardiac performance during the hyperdynamic response to sepsis in the presence of adequate volume support. PMID- 2316678 TI - Diurnal variations in vagal and sympathetic cardiac control. AB - To investigate the diurnal variation in autonomic cardiac control, the magnitudes of the power spectral components of supine and standing heart rate variability were measured during controlled respiration (15 breaths/min). Examination was performed hourly between 0700 and 2300 h in eight male subjects whose activities and food intake were controlled for 24 h in the laboratory. The respiratory component (0.25 Hz) was greater in the morning than in the late afternoon (P less than 0.05) and decreased 30 min after food intake (P less than 0.01) in the supine position, but it was unaffected by the time of day or food intake while in the standing position. The Mayer wave component (0.03-0.15 Hz) did not change with the time of day, but it increased 90 min after food intake in both supine and standing positions (P less than 0.01 and P less than 0.05, respectively). These data suggest that supine vagal cardiac control during the waking period increases in the morning and decreases 30 min after food intake and that sympathetic cardiac control increases 90 min after food intake. PMID- 2316679 TI - Heparinase treatment suggests a role for the endothelial cell glycocalyx in regulation of capillary hematocrit. AB - Physiological stimuli induce rapid and unexplained increases in the number of red blood cells within capillaries of skeletal muscle. We hypothesized that such alterations in intracapillary red cell numbers might be due to an undefined interaction between one or more components of blood and the luminal surface of the capillary. This proposition was tested by in situ microperfusion of capillaries with enzymes directed against macromolecules likely to be expressed on the surface of endothelial cells. The instantaneous fractional volume of red blood cells within a capillary (tube hematocrit) was used as an index of a capillary's response to enzyme microperfusion. Five to 8 min of perfusion with enzyme vehicle (0.25% albumin-Ringer solution) produced no significant alteration in capillary tube hematocrit. Perfusion with solutions containing heparinase raised the tube hematocrit at least twofold (P less than 0.05) without a significant change in red cell velocity. Heat-denatured heparinase and other enzymes such as neuraminidase, hyaluronidase, papain, pronase E, and clostripain had no detectable effect on the tube hematocrit (P greater than 0.05). After enzyme treatment, application of adenosine (10(-4) M) or oxygen caused brisk vasomotor responses in arterioles feeding perfused capillary units, but the usual changes in the tube hematocrit were not observed. Thus heparinase treatment results in a sustained elevation in the capillary tube hematocrit and a dissociation of the typical relationship between vasomotor changes and red cell distribution in capillaries. These findings suggest that physiological stimuli which alter the number of red blood cells within capillaries may operate by modifying interactions between plasma and one or more components on the luminal surface of capillaries. PMID- 2316680 TI - Flow-induced resistance artery tone: balance between constrictor and dilator mechanisms. AB - Infusion of physiological saline solution into the lumen of an isolated segment of a resistance artery results in constriction when the vessel is relaxed and in dilation when it is contracted. There is a level of wall tone at which infusion causes no change. In the small rabbit ear arteries used in this study (approximately 200 microns OD) this balance (null) point for infusion rates of 35 microliters/min is 69 +/- 4% of the maximum possible tone development. When tone is set at different levels by norepinephrine, infusion tends to change the level of wall force in the direction of the null point for that artery. The magnitude of flow-induced relaxation can be correlated positively (r = 0.74; P less than 0.001) and the flow-induced constriction correlated negatively (r = -0.67; P less than 0.001) with the level of wall tone. The 95% confidence prediction bands for flow relaxation and contraction against level of wall tone overlap when extrapolated to zero response. These results are consistent with the hypothesis that flow-induced change in resistance artery tone is the result of a balance between independent constrictor and dilator influences. PMID- 2316681 TI - Effects of increased splenic arterial flow and venous pressure on splenic red cell accumulation. AB - The importance of increments in splenic venous pressure (SVP) and splenic arterial flow (SAF) for splenic red cell accumulation was estimated in 14 anesthetized dogs with the spleen in situ by arterial and splenic venous hematocrit measurements and continuous ultrasonic recording of splenic diameter (SD). A 10-mmHg increase in SVP by 4 min of splenic venous constriction reduced SAF by 32 +/- 5%, increased SD by 5.1 +/- 0.8%, and transiently reduced splenic venous hematocrit, measured every 10 s, from 35.4 +/- 1.4 to a minimum of 29.2 +/ 1.8%. A 10-mmHg rise in SVP by 4 min of saline infusion increased SAF by 178 +/- 25% and SD by 16.1 +/- 3.0%, and splenic venous hematocrit declined more rapidly and to a lower value than arterial hematocrit. Blood volume expansion with saline or blood at constant, 10-mmHg elevated SVP confirmed that splenic red cell accumulation was greater during blood volume expansion than during splenic venous constriction. We conclude that the spleen accumulates red cells when SVP is raised. At constant, elevated SVP splenic red cell accumulation is flow dependent. PMID- 2316682 TI - Intramural coronary collateral flow in dogs. AB - The objective of this study was to determine whether intramural collaterals contribute significantly to total retrograde flow (index of collateral flow). The left circumflex, left anterior descending, right, and septal coronary arteries were separately cannulated, and blood flows through these vessels were monitored on an isolated, blood-perfused beating heart preparation. Epicardial collaterals between the borders of the circumflex and right coronary perfusion territories were cauterized, and retrograde flow from the circumflex coronary artery was determined before and after cauterization. This procedure unmasked the intramural collateral flow component to retrograde flow. By occluding and unoccluding the coronary flows from the right, septal, and left anterior descending coronary arteries during these measurements, we were able to determine their contribution to epicardial and intramural collateral flow. We found that, after cauterization, an average of 58 +/- 3.6% of the total retrograde flow remained. The septal and left anterior descending coronary arteries contributed almost equally to this retrograde flow. We concluded that, because the epicardial collaterals were cauterized, the source of retrograde flow was from intramural collaterals and constituted about one-half of the measured retrograde flow in dogs with a native collateral circulation. PMID- 2316683 TI - Energetic response of coronary endothelial cells to hypoxia. AB - The response of endothelial energy metabolism to oxygen supply was studied in cultured coronary endothelial cells from the rat at defined PO2 levels between 0.1 and 100 Torr. In the presence of glucose (5 mM), endothelial respiration (4 nmol O2.min-1.mg protein-1) was independent of the exterior PO2 greater than 3 Torr; oxygen consumption was half maximal at 0.8 Torr. At 100 Torr, lactate production was 26 nmol.min-1.mg protein-1; the decrease of the PO2 to 0.1 Torr resulted in a 2.2-fold increase in lactate production. The contents of ATP, ADP, and AMP were 21, 4, and 2 nmol/mg protein, respectively; they remained constant for 2.5-h incubations at PO2 levels between 0.1 and 100 Torr. In the presence of palmitate (100 microM) plus glutamine (0.5 mM), oxygen consumption was 8 nmol.min 1.mg protein-1 at PO2 levels greater than 3 Torr, and the half-maximal rate was again observed at 0.8 Torr. Lactate production was negligible. At PO2 levels greater than 3 Torr, the cells remained well energized. Below 3 Torr, however, the adenine nucleotide contents rapidly declined. These results demonstrate that the oxygen demand of coronary endothelial cells is low compared with the beating myocardium. In the presence of glucose, aerobic glycolysis is pronounced and the Pasteur effect small. In severe hypoxia (PO2 less than 0.1 Torr) the energetic state remained stable. In the absence of glucose, the energetic state of coronary endothelial cells is sensitive to the exterior PO2 less than 3 Torr, declining concomitantly with the decrease in respiration. PMID- 2316684 TI - Mechanism of L-glucose, raffinose, and inulin transport across intact blood-brain barriers. AB - Brain capillary permeability-surface area products (PS) of hydrophilic solutes were evaluated in terms of a conventional two-compartment model. In rats whose blood-brain barrier (BBB) was presumed to be intact, metabolically inert carbohydrates with different molecular weights were injected in pairs to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. The distribution volume of 70 kDa dextran 10 min after intravenous injection was used as a measure of the residual volume of plasma in brain tissue after death. The two-compartment model yielded larger PS values for inulin and raffinose than for L-glucose, and the PS values of inulin and L-glucose were found to decrease as the labeling time was lengthened (10, 30, and 60 min). These observations were interpreted to mean that a rapidly equilibrating compartment was present between blood and brain, rendering the two-compartment model inadequate for computing true transfer rate constants. When multiple-time uptake data were reanalyzed using the three compartment graphical analysis of Patlak, Blasberg, and Fenstermacher (J. Cereb. Blood Flow Metab. 3: 1-7, 1983), solutes of differing molecular size were found to enter the brain at approximately equal rates. This observation suggested that the predominant transport mechanism across an intact BBB is vesicular. Specifically, unidirectional transport is likely to be initiated by solute binding to the glycocalyx on the luminal surface of brain capillary endothelium. Apparently more inulin than L-glucose is absorbed, which may account for its slightly faster transfer across the BBB. We suggest that this adsorptive surface is the location of the rapidly equilibrating compartment on the plasma side of the BBB. PMID- 2316685 TI - Inhibition of renal sympathetic activity and heart rate by vasopressin in hemorrhaged diabetes insipidus rats. AB - Hypotensive hemorrhage paradoxically decreases renal sympathetic nerve activity (SNA) and heart rate (HR) in normal rats. Interruption of vagal reflexes by cervical vagotomy prevents these inhibitory responses but does not unmask expected increases in either renal SNA or HR. Arginine vasopressin (AVP), which increases markedly during hemorrhage, may also exert an inhibitory action on responses of renal SNA and HR to hemorrhage. We tested the hypothesis that inhibition of renal SNA and HR by hemorrhage is absent in AVP-deficient diabetes insipidus (DI) rats and is restored by intravenous AVP replacement (1 mU.kg-1.min 1 before hemorrhage and 10 mU.kg-1.min-1 during hemorrhage). We also determined whether vagotomy unmasks significant increases in renal SNA and HR during hemorrhage in DI rats and whether AVP replacement prevents these increases. Under chloralose anesthesia, hemorrhage to 50 mmHg mean arterial pressure for 8 min did not decrease renal SNA or HR in AVP-deficient DI rats but decreased (P less than 0.05) renal SNA and HR in normal Long-Evans rats and in DI rats receiving AVP replacement. After vagotomy, hemorrhage increased (P less than 0.05) renal SNA and HR in AVP-deficient DI rats but did not alter renal SNA or HR in Long-Evans rats and AVP-treated DI rats. Thus renal SNA and HR during hemorrhage were consistently higher (P less than 0.05) in AVP-deficient DI rats compared with Long-Evans or AVP-treated DI rats both before and after vagotomy. In addition, vagotomy attenuated the inhibitory action of AVP on the response of HR but not the response of renal SNA to hemorrhage in DI rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316686 TI - Heart rate and muscle sympathetic nerve variability during reflex changes of autonomic activity. AB - Low-frequency (less than 0.15 Hz) fluctuations of heart rate are increased by maneuvers, such as standing or hemorrhage, that increase sympathetic outflow to the heart and vasculature. To test the hypothesis that low-frequency heart rate fluctuations provide an index of sympathetic efferent activity, we compared power spectral measures of heart rate variability with two measures of sympathetic outflow, peroneal nerve sympathetic activity and antecubital vein plasma norepinephrine concentrations. Autonomic outflow was varied with graded stepwise infusions of nitroprusside and phenylephrine, which lowered or raised average diastolic pressures by approximately 15 mmHg. Before vasoactive drug infusions, no spectral measure of heart rate variability correlated significantly with muscle sympathetic activity, plasma norepinephrine concentration, average heart rate, or arterial pressure. During increases of muscle sympathetic activity and probable reductions of cardiac vagal activity induced by nitroprusside, the fraction of heart rate spectral power at low frequencies, but not the absolute value, correlated significantly with muscle sympathetic activity and plasma norepinephrine. However, during reductions of muscle sympathetic activity and probable elevations of cardiac vagal activity induced by phenylephrine, no measure of heart rate variability correlated significantly with muscle sympathetic activity. These findings can be explained by a model of heart rate control in which low-frequency heart rate fluctuations result from changing levels of both the sympathetic and parasympathetic inputs to the sinoatrial node. PMID- 2316687 TI - Arginine vasopressin increases apparent whole body capacity in anesthetized cats. AB - The effects of arginine vasopressin (AVP) on capacitance function were assessed in anesthetized cats by draining blood from the superior and inferior venae cavae into an external reservoir and then returning blood to the right atrium at a constant rate. Under these conditions, changes in reservoir volume were assumed to reflect reciprocal changes in whole body capacity. Intravenous infusions of AVP (1, 10, and 100 ng.kg-1.min-1) that elevated plasma AVP concentrations by approximately 30, 400, and 4,000 fmol/ml were associated with concentration dependent increases in whole body capacity that ranged between 1.6 and 8 ml/kg. In contrast to AVP, intravenous infusions of angiotensin II (5, 10, and 50 ng.kg 1.min-1) had relatively little influence on capacity, whereas norepinephrine administration (300, 1,000, and 3,000 ng.kg-1.min-1) was associated with dose dependent decreases in capacity of 4.5-10.3 ml/kg. Virtually the entire increase in whole body capacity to AVP can be accounted for by summation of the predicted contributions of an active reflex venodilatatory component and those of a passive component (arterial and cardiopulmonary compartments). Because systemic compliance (delta reservoir volume/delta venous pressure) was not changed by AVP administration, the contribution of a reflex venodilatatory component must be the result of increases in unstressed vascular volume (contained volume at 0 transmural pressure) as opposed to changes in compliance. These results may explain why AVP decreases cardiac output to a greater extent than either angiotensin II or sympathomimetics and, thus, why AVP is a weaker pressor agent in animals with intact autonomic function. PMID- 2316689 TI - Phase resetting in a model of sinoatrial nodal membrane: ionic and topological aspects. AB - We describe the phase-resetting effect of injecting an isolated current pulse in an ionic model of a single cell of the sinoatrial node. Delivery of a depolarizing pulse early (late) in the cycle results in a prolongation (abbreviation) of the cycle length. With a hyperpolarizing pulse, the effect is reversed. We determine the topological type or degree of phase resetting in two ways: 1) by analyzing interbeat intervals extracted from the voltage waveform, and 2) by analyzing the waveform, not only of the voltage, but of all the activation and inactivation variables. The two methods give similar results. At low (high) pulse amplitudes, there is type 1 (0) phase resetting. When type 1 phase resetting occurs, the new phase is a monotonically increasing function of the old phase at sufficiently low stimulus amplitudes, whereas at higher stimulus amplitudes it is not. Leading roles in generating phase resetting are attributed to the slow inward current and to the leakage current. Comparison is made with experimental phase-resetting findings in the sinoatrial node and other cardiac oscillators. Implications for unidirectional and bidirectional synchronization are also sketched out. PMID- 2316688 TI - Cerebral blood flow during fastigial pressor response in cats. AB - We tested the hypotheses that electrical stimulation of the fastigial nucleus increases cerebral blood flow by a dilator mechanism, impairs autoregulation during increases in arterial pressure, and attenuates increases in cerebral blood flow during acute hypertension by activation of sympathetic nerves. Cerebral blood flow was measured with microspheres in anesthetized cats during control and moderate or severe hypertension produced by stimulation of the rostral fastigial nucleus. Cervical sympathetic nerves to one cerebral hemisphere were cut to compare responses in the innervated and denervated hemispheres. Fastigial stimulation at a level that raised arterial pressure from 94 +/- 10 (mean +/- SE) to 133 +/- 6 mmHg had no significant effect on cerebral blood flow. Autoregulation was preserved because cerebral vascular resistance increased approximately 40% during the fastigial pressure response. When mean arterial pressure was raised to 189 +/- 9 mmHg by stimulation of the fastigial nucleus, cerebral blood flow increased similarly in the denervated hemisphere and the hemisphere with intact sympathetic nerves. We conclude that stimulation of the fastigial nucleus in cats does not have a direct dilator effect on cerebral vessels, does not impair autoregulation during moderate hypertension, and does not attenuate increases in cerebral blood flow during severe hypertension by activation of sympathetic pathways. PMID- 2316690 TI - Macromolecular transport in canine coronary microvasculature. AB - Coronary vascular osmotic reflection coefficients (sigma dS) for total protein, albumin (Alb), immunoglobulin (Ig)G, and IgM were determined in the anesthetized dog. Myocardial lymph was collected from the anterior interventricular lymphatic trunk, and the sigma dS estimated from filtration rate-independent lymph-to plasma protein concentration ratios (CL/CPS). Lymph flows of at least 12 times base line were needed to produce filtration rate-independent CL/CPS, and these were achieved in 9 of 12 experiments. In these nine experiments, sigma dS for total protein, Alb, IgG, and IgM were, respectively, 0.67 +/- 0.02 (SE), 0.59 +/- 0.05, 0.70 +/- 0.03, and 0.87 +/- 0.01. The data were fitted to a model that showed that transvascular fluid and solute flux could be described by two populations of pores. A large pore system with an equivalent radius of 235 A was responsible for 39% of the transvascular volume flow. A small pore system less than 53 A accounted for the remaining flow. In a second group of experiments (n = 8), 60 min of ischemia decreased the sigma dS to 0.27 +/- 0.03, 0.07 +/- 0.05, 0.22 +/- 0.03, and 0.69 +/- 0.04 for total protein, Alb, IgG, and IgM, respectively. A single population of pores of 220 A could describe the entire transvascular volume flow. These results indicate that coronary vascular protein permeability is moderately high and can be increased significantly by ischemia. PMID- 2316692 TI - Muscle blood flow in trained rats with peripheral arterial insufficiency. AB - The influence of exercise training on the recovery of muscle blood flow was assessed in rats with bilateral stenosis of the femoral artery, sufficient to limit exercise hyperemia in the distal hindlimb but not alter resting blood flow. Muscle blood flow was measured with 141Ce-labeled microspheres (15 microns) during treadmill running at 20 m/min in normal (n = 10), acute stenosed (n = 9), sedentary stenosed (n = 10) and trained stenosed (n = 13) animals. Treadmill training by a progressively intense program (up to 1 h/day, 7 days/wk for 6 wk) improved exercise tolerance evident both in duration and intensity of exercise. Total hindlimb blood flow (ml.min-1.100 g-1) was not different (P greater than 0.05) between all stenosed groups but was only 46-63% that of the normal group (P less than 0.05). Acute stenosis reduced distal blood flow to only 22% of that in the proximal hindlimb tissue. A significant (P less than 0.05) but limited recovery of distal limb blood flow (to 44% of proximal) occurred in sedentary stenosed rats after 6 wk of cage activity. Training further increased (P less than 0.05) distal limb blood flow to 69% of proximal. This partial recovery of distal limb blood flow could reflect a greater collateral vessel function or an enhanced vascularity of the distal limb tissue. Our results illustrate that peripheral adaptations occur within the ischemic hindlimb of trained animals to redistribute the limited O2 delivery to the active muscles most affected by stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316691 TI - Pulmonary embolism: emboli and fibrinolysis inhibition in isolated canine lungs. AB - The effect of fibrinolysis inhibition with tranexamic acid on pulmonary microvascular permeability during glass bead embolization was investigated in the isolated lung. Lung lobes from nonheparinized dogs were treated in vivo with the equivalent of 0.6 g/kg 100 microns glass bead emboli alone, emboli after tranexamic acid, tranexamic acid alone, or the bead vehicle alone. After 40-50 min, the lobes were isolated for ex vivo perfusion with heparinized autologous blood. There were no changes in any parameter over the 120-min perfusion period. Blood flow at 120 min was decreased after both emboli alone and emboli with tranexamic acid, reflecting an increase in vascular resistance compared with the Tween or tranexamic acid controls. Furthermore, tranexamic acid increased the ratio of pre- to postcapillary resistance in embolized lobes compared with that after emboli alone or in the Tween or tranexamic acid controls. The isogravimetric capillary pressure and the osmotic reflection coefficient were not significantly decreased by tranexamic acid compared with those after emboli alone; however, it did result in an increase in the capillary filtration coefficient compared with that after emboli alone or in the control groups. We conclude that although fibrinolysis inhibition does not clearly exacerbate the lung injury seen after emboli, the tranexamic acid-induced changes in hemodynamics would tend to accelerate edema formation. PMID- 2316693 TI - Brachial artery diameter changes associated with cardiopulmonary baroreflex activation in humans. AB - Stimulation of receptors in the cardiopulmonary compartment produces a vasodilatation of forearm resistive vessels. A possible participation of large conduit arteries in such adjustments, studied in situ, has not been clearly documented in humans. We used a dual-crystal pulsed Doppler system to determine whether leg elevation in recumbent subjects is associated with changes in brachial artery diameter (BAD) and blood velocity (BV) in humans. BA diameter, velocity, and flow, together with arterial pressure and heart rate, were measured in 20 normal subjects in supine position and after passive leg raising. BAD increased immediately after leg elevation from 4.03 +/- 0.11 to 4.56 +/- 0.13 mm (P less than 0.001) parallel with an increase in BV from 6.05 +/- 1.18 to 7.1 +/- 1.36 cm/s (P less than 0.02). A positive correlation between BAD enlargement and BV increase was observed during the initial peak response (P less than 0.01). Subsequent measures indicated that BAD remained enlarged throughout the whole period of leg raising, whereas BV returned to the base-line values. Brachial artery volumic flow augmented during the initial phase of leg raising from 46 +/- 8 to 74 +/- 15.5 ml/min (P less than 0.01) and remained elevated throughout the whole period of leg elevation. This study shows that arteries participate in hemodynamic adjustments induced by positional changes associated with cardiopulmonary baroreflex activation. PMID- 2316694 TI - Sensory nerves mediate neurogenic escape in rat gut. AB - We investigated the involvement of primary sensory nerves in intestinal autoregulatory escape induced by postganglionic nerve stimulation (NS) in anesthetized rats. Anterior mesenteric artery (AMA) blood flow velocity (BF) was measured with a pulsed Doppler flowmeter. Periarterial NS elicited an abrupt fall in BF, which was followed by a recovery in BF toward the basal value, despite sustained NS. This recovery from NS constituted the neurogenic escape phenomenon. Vasoconstrictor responses to NS were abolished by periarterial application of tetrodotoxin. Acute, surgical interruption of proximal periarterial nerves had no effect on BF responses to distal NS, suggesting a peripheral rather than a central nervous mechanism for the escape phenomenon. Escape from NS-induced vasoconstriction was significantly inhibited by prior administration of the selective sensory neurotoxin capsaicin as either subcutaneous injection in neonatal life, acute application to periarterial nerves, or acute injection into the jejunal lumen. In rats pretreated 24 h with reserpine, NS provoked a vasodilator response that was inhibited by intrajejunal capsaicin. Increases in arterial blood pressure (BP) and heart rate observed during NS were blocked by periarterial (but not intrajejunal) application of capsaicin. Transmural electrical field stimulation elicited significantly greater nerve-induced contractions in AMA rings from control rats. Our findings support the hypothesis that postganglionic NS activates both vasoconstrictor sympathetic nerve branches and vasodilator afferent C-fibers. The latter nerves release vasodilator peptides in the periphery during continuous low frequency NS that appear to be essential for autoregulatory escaped in our model. PMID- 2316696 TI - Effect of acidosis and alkalosis on postischemic Ca gain in isolated rat heart. AB - The effect of pH of the reperfusion buffer on postischemic changes in tissue Ca and Na was examined in isolated Langendorff-perfused Sprague-Dawley rat hearts. Reperfusion began after 15-, 25-, or 60-min ischemia at 37 degrees C. After 60 min ischemia, reperfusion at pH 6.4 or 6.6 attenuated the reperfusion-induced Ca gain so long as the acidotic conditions were maintained (3.08 +/- 0.22, 1.37 +/- 0.41, and 16.96 +/- 1.18 mumol Ca gain/g dry wt for pH 6.4, 6.6, and 7.4, respectively after 15-min reperfusion). Conversely, reperfusion under alkalotic conditions (pH 7.9) after 60-min ischemia exacerbated the gain (27.45 +/- 4.75 and 8.92 +/- 1.53 mumol Ca gain/g dry wt during 5-min reperfusion at pH 7.9 and 7.4, respectively). Similar, but less pronounced Ca gains occurred during reperfusion after 15- or 25-min ischemia. Sodium content during reperfusion, but not during aerobic perfusion, was also found to be pH sensitive with acidosis causing a reduction and alkalosis an increase. These results could not be explained in terms of an effect of pH on recovery of high-energy phosphates, percentage "reflow" during reperfusion, or reperfusion-induced increases in tissue water or resting tension. The results are in agreement with the hypothesis that the "inhibitory" effect of acidosis on postischemic Ca overload could involve an effect of pH on the Na(+)-H+ exchanger and intracellular Ca storage. PMID- 2316695 TI - Positive pleural pressure decreases coronary perfusion. AB - Pressure surrounding the heart (PSH) rises with maneuvers that increase pleural pressure. This may decrease left ventricular (LV) oxygen demand by reducing LV afterload. However, positive PSH may also directly impede coronary flow. To study the effects of positive PSH on coronary perfusion, PSH was increased in 10-mmHg increments from 0 to 60 mmHg in an isolated canine heart-lung preparation with constant venous return, arterial pressure, and lung volume. Increased PSH caused a rapid significant (P less than 0.001) fall in left atrial transmural pressure (PLATM) of up to 1.28 +/- 0.31 mmHg. With constant venous return and lung volume, this was interpreted to reflect decreased LV afterload. However, at levels of PSH greater than 30 mmHg, initial decreases in PLATM were followed by sustained increases, suggesting that there was a deterioration in cardiac function despite the lower level of afterload. Increased PSH was also associated with decreases in circumflex coronary artery flow [flow (ml/min) = 52.4 - 0.4PSH, P less than 0.01]. Moreover, when the circumflex coronary artery was maximally dilated with adenosine, the effects of PSH were amplified [flow (ml/min) = 137.9 - 1.78PSH, P less than 0.001], indicating that positive PSH mechanically impeded coronary flow. When PSH was raised to 60 mmHg for 90 s, the aortic-coronary sinus lactate concentration difference fell from 0.71 +/- 0.09 to 0.10 +/- 0.21 mM (mean +/- SE, P less than 0.001, n = 8), suggesting myocardial ischemia. We conclude that positive PSH directly decreases myocardial perfusion. This may lead to ischemic cardiac dysfunction, especially in patients with low arterial pressure or coronary artery disease. PMID- 2316697 TI - Endothelial and smooth muscle cells hyperpolarized by bradykinin are not dye coupled. AB - The membrane potential of endothelial and neighboring (0.1 mm) smooth muscle cells of pig coronary arteries were simultaneously recorded with two microelectrodes. The membrane potential of endothelial cells was -40 +/- 4 mV (n = 9). In these cells bradykinin (250 nM), an endothelium-dependent vasodilator, evoked a transient hyperpolarization (14 +/- 2 mV, n = 9) resembling those already observed in smooth muscles. The similarity between the electrical signal of pre- and postmyoendothelial junctions suggested an electrical coupling between endothelial and smooth muscle cells. However, the injection of the fluorescent dye Lucifer yellow in the recorded cell proved that the cell was endothelial, and in addition, the injection demonstrated the absence of dye coupling between endothelial and smooth muscle cells. Moreover the injection of electrical pulses (0.05-3.5 nA) in the endothelial cell never evoked any electrical response in the smooth muscle. By contrast, the smooth muscle cells were electrically coupled together. These results do not support the idea that the endothelial cell hyperpolarization caused by bradykinin is transmitted to smooth muscle cells by electrotonic spreading. PMID- 2316698 TI - Regional vascular resistance during exercise: role of cardiac afferents and exercise training. AB - This study was designed to determine whether cardiac vagal afferents exert an inhibitory influence on increases in regional vascular resistance during exercise and to determine whether endurance exercise training enhances the inhibitory influence of cardiac vagal afferents. We measured changes in regional vascular resistance in 12 rabbits at rest and during running at 12.6 m/min, 20% grade, before and after reversible denervation of cardiac afferents (intrapericardial procainamide HCl, 2%). In addition, these procedures were repeated in five of these rabbits following an 8-wk endurance exercise training program. Because intrapericardial injections of procainamide anesthetize both the efferent as well as the afferent innervation to the heart, it was necessary to determine the effects of blocking the efferent innervation on the regulation of regional vascular resistance during exercise. Rabbits were instrumented with Doppler ultrasonic flow probes around the renal (R), mesenteric (M), ascending, and terminal aortic (TA) arteries. Catheters were positioned in the central ear artery and vein and pericardial sac. Mean arterial pressure, heart rate, cardiac output, R, M, TA, and systemic (S) resistances were determined. Exercise changed R (+37 +/- 4%), M (+88 +/- 9%), TA (-62 +/- 6%), and S (-34 +/- 3) resistances. Subsequent cardiac efferent blockade alone had no significant effect on regional vascular resistance during exercise. Combined efferent and afferent blockade resulted in significant increases in R (+62 +/- 6%) and M resistance (+134 +/- 13%) but did not alter TA (-51 +/- 4%) or S (-27 +/- 2%) resistance during exercise. Exercise training significantly enhanced the inhibitory influence of cardiac afferents on R and M regional vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316699 TI - Altered pressor responses to NE and ANG II during cyclosporin A administration to conscious rats. AB - Vasoconstriction and hypertension have been prominent during cyclosporin A (CSA) administration. To evaluate whether CSA modulates vascular responsiveness to pressor stimuli in the intact organism, CSA was administered via osmotic pump (10 and 20 mg.kg-1.day-1 ip vs. olive oil vehicle) for 2 wk. After 8 days, arterial pressure and dose-response relationships to norepinephrine, angiotensin II, and bradykinin were measured in conscious animals. Despite similar initial pressures, dose-response relationships were markedly attenuated to both norepinephrine and angiotensin II. Maximal responses were not affected, indicating a rightward shift without loss of peak effect. Vasodilation with bradykinin was not diminished. These changes were not evident after an acute CSA infusion at the same dose (10 mg.kg-1.day-1 over 2 h). Treatment with verapamil (0.505 mg/kg over 2 days) lowered basal arterial pressures but did not change the effects of CSA on pressor sensitivity. Despite attenuated pressor responses, renal vascular resistance was elevated and glomerular filtration diminished during CSA administration. These observations indicate that cyclosporin modifies vascular responsiveness to pressor stimuli in the rat and may explain the relative resistance of this species to cyclosporin-induced hypertension. PMID- 2316700 TI - Unstimulated force during hypoxia of rat cardiac muscle: stiffness and calcium dependence. AB - The stiffness of rat cardiac trabeculae was measured in vitro to distinguish between an increase in unstimulated force (Fu) caused by rapid cycling of cross bridges or caused by rigor bridges during hypoxia. The force was measured with a strain gauge, the sarcomere length was determined by laser diffraction techniques, and muscle length was controlled by means of a motor. Stiffness was analyzed by using small (less than 1% of muscle length) sinusoidal length perturbations of 1 and 100 Hz. The stiffness at 100 Hz increased linearly with force during tetani at a varied [Sr2+] (0.25-10 mM) in the Krebs-Henseleit (K-H) buffer, but remained virtually unchanged at 1 Hz. In contrast, the stiffness of both the passive muscle and the muscle exposed to either CN- or to PO2 less than 1.5 mmHg up to development of maximal Fu (Fumax) was similar at 1- and 100-Hz perturbations. Less profound hypoxia (PO2 6-10 mmHg) resulted in spontaneous sarcomere activity during the rise in Fu, and an increase in the ratio of stiffness at 100 Hz to stiffness at 1 Hz was detected. When oxidative phosphorylation was inhibited by CN- (2 mM) while the muscle was stimulated in the absence of both Ca2+ and Na+ (choline+substituted), the addition of Na+ at the time at which Fu had reached 30-40% of Fumax did not affect the rate of rise of Fu. These results show that the development of Fu during more complete anoxia in rat trabeculae is completely due to the formation of rigor links and that Ca2(+)-dependent cross-bridge activation can contribute to the rise in Fu during less severe hypoxia. PMID- 2316701 TI - Heat production in isolated heart myocytes: differences among species. AB - A new calorimetry method has been developed to measure heat production from heart cell suspensions under continuous perfusion. The method is technically independent of the temperature at which the measurements are made, allows full control of the perfusion media, and is suitable for various biological preparations such as cells from diverse tissues, membrane vesicles, or skinned cells. The resting heat rate (Hr) measured at 18.5 degrees C in three different species (19.2 +/- 0.43, 12.8 +/- 0.56, and 9.4 +/- 0.52 mW/g dry wt for rat, guinea pig, and rabbit ventricular myocytes, respectively) agrees with that obtained with other methodologies such as oxygen consumption, thermopiles, and whole heart calorimetry. The Hr measurements showed an excellent correlation with the percentage of rod-shaped cells, indicating that rounded cells are metabolically inactive. Although the time course of the effect of increasing extracellular [K] was dependent on the species, the new steady level of Hr observed under higher extracellular [K] was significantly higher in all three species (+8.3 +/- 1.2, +9.5 +/- 4.0, and +9.3 +/- 2.7 mW/g dry wt for rat, guinea pig, and rabbit ventricular cells, respectively). This indicates that the commonly used "arrested-heart" preparation (with high extracellular [K]) for evaluation of basal metabolism most probably overestimates the real resting values. The present results also show that the wide range of resting metabolism reported in whole tissue is not due to cellular heterogeneity nor to myocyte interaction and supports the idea of an inverse relationship between resting metabolism and body weight or animal size across species. PMID- 2316702 TI - A new method to identify dynamic transduction properties of aortic baroreceptors. AB - We identified, in 17 alpha-chloralose-anesthetized rabbits, the dynamic transduction characteristics of the aortic arch baroreceptors using a "white noise technique." We recorded aortic pressure and aortic depressor nerve activity while perturbing pressure by rapid, intermittent ventricular pacing (400 beats/min). Dividing the cross-power spectrum between nerve activity and pressure by the power spectrum of pressure yielded the transfer function. The gain of the transfer function increased threefold as the frequency increased from 0.005 to 5 Hz, suggesting that the baroreceptors responded primarily to dynamic rather than to static changes in pressure. To quantify the nonlinear properties of baroreceptor transduction, we compared measured instantaneous nerve activity with that linearly predicted. We demonstrated that the major nonlinearity was attributable to "threshold". The overall baroreceptor transduction properties could be represented by a cascade connection of a linear subsystem followed by a nonlinear subsystem with threshold. The white-noise technique made it possible to identify the unbiased linear properties in a nonlinear system, and thus was very useful in identifying complex biological systems. PMID- 2316703 TI - ANG II inhibits calcium-activated potassium channels from coronary smooth muscle in lipid bilayers. AB - Angiotensin II (ANG II) is a powerful vasoconstrictor of coronary vessels and other smooth muscles. One of the actions of ANG II is the inhibition of K+ currents, possibly contributing to depolarization and contraction. Therefore, we investigated the role of ANG II on the regulation of K+ channels at the single channel level. We studied its effect on calcium-activated potassium (KCa) channels (congruent to 250 pS) from coronary smooth muscle incorporated into lipid bilayers. KCa channels were sensitive to externally applied ANG II at voltages from -20 to -70 mV and pCa between 6.5 and 4. The dose-response curve gave a concentration of half-inhibition (Ki1/2) of 58 nM and a Hill coefficient of 2.2, indicating a minimum of two sites in the process. ANG II modified the open and closed states of the channel, affecting their proportions and their values. In addition, a new much slower (congruent to 1 s) closed or "blocked" state appeared. We conclude that one of the mechanisms by which ANG II causes vasoconstriction of the coronary vessels is a direct inhibition of KCa channels contributing to depolarization and contraction. PMID- 2316704 TI - Endothelium regulates skeletal muscle microcirculation by a blood flow velocity sensing mechanism. AB - In rat cremaster muscle, utilizing parallel arteriolar occlusion, we found that an increase in red blood cell (RBC) velocity (3.5-26.5 mm/s) per se induced an increase in diameter (1.5-9.4 microns) of arterioles (mean control diam 21.5 +/- 0.6 microns; n = 25). The dilation of arterioles appeared only when RBC velocity increased and started always with a delay (mean 8.4 +/- 0.5 s) after the increase in flow velocity. A positive linear correlation was found between peak changes in RBC velocity and diameter (r = 0.87, P less than 0.05). The velocity sensor as well as the mechanism(s) that mediates this response is likely to be located in endothelial cells, because the dilation to increased RBC velocity was completely eliminated after impairment of arteriolar endothelium with light-dye (L-D) treatment. The in vivo demonstration of this phenomenon in arterioles suggests the existence of a new endothelium-dependent, flow velocity-sensitive mechanism for the regulation of blood flow in the microcirculation. PMID- 2316705 TI - Pressure-flow characteristics of coronary collaterals in dogs. PMID- 2316706 TI - Model of placental glucose consumption and glucose transfer. AB - Net ovine uteroplacental glucose consumption (Ro,up) and transfer rates to the fetus (Rf,up) were measured at different concentrations of maternal (GA) and fetal (Ga) arterial plasma glucose that were set and maintained independently by a glucose clamp procedure. Five GA/Ga combinations were studied: 70/15, 70/20, 70/30, 50/14, and 50/24 mg/dl. Rf,up was inversely related to Ga both at GA = 70 and GA = 50. Linear regression analysis of Rf,up vs. Ga for the GA = 70 and GA = 50 groups of observations revealed similar slopes (-0.286 +/- 0.012 vs. -0.217 +/ 0.028 dl.min-1.kg fetus-1) but a significantly higher intercept for the GA = 70 group (10.3 +/- 0.12 vs. 5.5 +/- 0.47 mg.min-1.kg fetus-1). In contrast, Ro,up increased significantly in response to an increase of Ga and had no significant dependence on GA. These results indicate that uteroplacental glucose metabolism occurs primarily in tissues that have direct access to glucose molecules carried by the umbilical circulation and that the glucose transport capacity of the placental barrier is greater on its fetal than its maternal surface. Uteroplacental glucose metabolic rate and its dependence on fetal glucose concentration are major factors that determine the magnitude and variability of the glucose concentration gradient (and thus the rate of net glucose transfer) between maternal and fetal plasma. PMID- 2316707 TI - Antiserum against tumor necrosis factor increases stress hyperthermia in rats. AB - Psychological stress (e.g., exposure to a novel environment) causes a rapid rise in body temperature in rats. In this study, we examined the roles of physical activity and the immune cytokine tumor necrosis factor or cachectin (TNF) in this temperature change. The elevation in temperature of rats exposed to cage-switch stress during the day correlated poorly with the increase in activity (r = 0.07; P = 0.84) and, during cage switch at night, correlated negatively (r = 0.64; P = 0.04). TNF was not detected in the plasma or cerebrospinal fluid of rats after exposure to open-field stress. However, the injection of antiserum against TNF 3.5 h before exposure to the stress of being in an open field resulted in a significantly greater hyperthermia than was seen in the control serum-injected rats (1.38 +/- 0.11 vs. 0.79 +/- 0.14 degrees C; P = 0.002). The peak temperature change after cage-switch stress was similarly increased in rats that had been injected with anti-TNF (0.82 +/- 0.08 vs. 0.50 +/- 0.08 degrees C; P = 0.016). This enhanced hyperthermia is similar to the excessively high fever that occurs during the later phase of lipopolysaccharide fever in animals that have been injected with antiserum against TNF. These data support the hypotheses that stress hyperthermia is a true fever and that TNF is an endogenous antipyretic, limiting the magnitude of this fever. PMID- 2316709 TI - Facial vessels of desert camel (Camelus dromedarius): role in brain cooling. AB - The reactivity of the superficial veins of the camel was investigated in vitro in response to stretch, heat, norepinephrine, and transmural nerve stimulation (TNS). Stretch at 30 degrees C or 37 degrees C produced a maintained tone and phasic contractions of the facial and nasal veins. The developed tone increased significantly with increasing the temperature (from 30 to 45 degrees C), especially in the proximal part of the buccal facial vein. Norepinephrine caused a constrictor response in the facial vein with the proximal part showing a lower maximum. TNS evoked a constrictor response in proximal segment and a dilator response in the more proximal segment of the buccal facial vein. Either responses were blocked by bretylium or tetrodotoxin. Morphological examination of the vasoactive segment of the facial vein showed a thick muscular layer and a valve in the proximal segment of the buccal facial vein. These results show functional variation in the distribution of adrenoceptors in the facial vein. The high temperature sensitivity of the buccal facial vein suggests that this part could serve as a temperature-sensitive sphincter that diverts cool nasal blood to the brain for selective cooling of the camel brain during heat stress. PMID- 2316708 TI - Central nervous system cardiovascular actions of CRF in sinoaortic-denervated rats. AB - Studies were performed in unrestrained conscious Sprague-Dawley rats to examine the central nervous system (CNS) mechanism by which corticotropin-releasing factor (CRF) produces simultaneous elevations of arterial pressure and heart rate. To test the hypothesis that CRF inhibits ongoing impulse transmission through and/or transmitter release from the CNS terminations of baroreceptor afferents, the cardiovascular effects of intracerebroventricular administration of CRF were compared in rats subjected to prior sham surgery (Sham) or sinoaortic denervation (SAD). Resting levels of arterial pressure and heart rate were elevated after SAD. In addition, SAD resulted in greater chronotropic sympathetic tone and reduced chronotropic parasympathetic tone as assessed by intravenous injections of atropine methyl nitrate and DL-propranolol. Intracerebroventricular administration of CRF in both surgical groups elicited significant increases in arterial pressure and heart rate, although a tendency for reduced tachycardic responses after SAD was apparent. Pretreatment with atropine or propranolol revealed that both the parasympathetic and sympathetic nervous systems contribute to CRF-induced heart rate responses in both surgical groups. These results suggest that ongoing baroreceptor afferent transmission is not requisite for the expression of CRF-induced cardiovascular changes. Thus it is unlikely that CRF elevates arterial pressure and heart rate through an exclusive action at the CNS terminations of baroreceptor sensory fibers. PMID- 2316710 TI - Weight gain and brown fat composition of mice selected for high body weight fed a high-fat diet. AB - Mice selected for high body weight (QL522) had increased food intake, body weight gain, and fat deposition relative to mice without weight selection (QL521). Brown adipose tissue (BAT) thermogenic capacity, as determined by the tissue content of protein, DNA, and succinate dehydrogenase and by mitochondrial uncoupling protein content was similar or slightly higher in 2- and 10-mo-old QL522 mice relative to age-matched QL521 mice. When food intake of QL522 mice was restricted to the level of QL521 mice, body weight gain and fat deposition over 28 days were then comparable to those of QL521 mice. Food restriction had no effect on BAT composition of QL522 mice. Both QL521 and QL522 mice increased calorie intake by 40-50% when offered a palatable high-fat supplement (HF), but only QL522 mice increased weight gain and fat deposition significantly. QL521 mice fed a high-fat supplement showed a significant increase in brown fat succinate dehydrogenase content, whereas QL522 mice showed significant increases in brown fat weight, protein, and succinate dehydrogenase content relative to mice fed stock diet. Nonshivering thermogenic capacity, as assessed by norepinephrine-stimulated oxygen uptake in anesthetized animals at 30 degrees C was similar between QL521 and QL522 mice eating stock diet and was significantly increased by the high-fat supplement in both strains. Thus mice selected for high body weight are very susceptible to diet-induced obesity, and we have no evidence that a reduction in brown fat thermogenic capacity contributes to the increased fat deposition of QL522 mice as they grow old or when they are offered palatable energy-dense supplements. PMID- 2316711 TI - Sleep regulation in rats during early development. AB - Sleep states and power spectra of the electroencephalogram (EEG) were determined in freely moving young rats. Recordings during 24 h were obtained from the same animals at three different ages. Already at the age of 23 days waking predominated in the 12-h dark period. Rapid-eye-movement sleep (REMS) declined between the age of 23 and 40 days. Its 24-h maximum was situated in the dark period at 23 and 29 days of age and in the light period at 40 days. Slow-wave activity (SWA; 0.75-4.0 Hz) of the non-REMS (NREMS) EEG showed marked age-related changes: a declining trend in the 12-h light period was absent at 23 days, moderate at 29 days, and prominent at 40 days. At 23 days, SWA progressively declined within ultradian sleep episodes and at 24 days was massively increased after 2-h sleep deprivation (SD). At the age of 30 days, 6-h SD induced much smaller changes. The distinct 24-h pattern of high-frequency activity (10.25-25.0 Hz) was present at all ages and may represent an EEG correlate of a circadian process. We conclude that homeostatic mechanisms regulating NREMS intensity are already operative a few days after weaning. PMID- 2316712 TI - Time course of EEG power density during long sleep in humans. AB - In nine subjects sleep was recorded under base-line conditions with a habitual bedtime (prior wakefulness 16 h; lights off at 2300 h) and during recovery from sleep deprivation with a phase-advanced bedtime (prior wakefulness 36 h; lights off at 1900 h). The duration of phase-advanced recovery sleep was greater than 12 h in all subjects. Spectral analysis of the sleep electroencephalogram (EEG) revealed that slow-wave activity (SWA; 0.75-4.5 Hz) in non-rapid-eye-movement (NREM) sleep was significantly enhanced during the first two NREM-REM sleep cycles of displaced recovery sleep. The sleep stages 3 and 4 (slow-wave sleep) and SWA decreased monotonically over the first three and four NREM-REM cycles of, respectively, base-line and recovery sleep. The time course of SWA in base-line and recovery sleep could be adequately described by an exponentially declining function with a horizontal asymptote. The results are in accordance with the two process model of sleep regulation in which it is assumed that SWA rises as a function of the duration of prior wakefulness and decreases exponentially as a function of prior sleep. We conclude that the present data do not provide evidence for a 12.5-h sleep-dependent rhythm of deep NREM sleep. PMID- 2316713 TI - Ingestion rate as an independent variable in the behavioral analysis of satiation. AB - A novel intake testing paradigm, allowing explicit adjustment of the rate of sucrose ingestion via intraoral delivery, was used to investigate the effects of ingestion rate on ingestion duration and amount consumed. In experiment I, 12 rats were tested under each of three sucrose concentrations (0.1, 0.3, and 1.0 M) delivered at each of four rates (0.5, 1.0, 1.5, and 2.0 ml/min). For each stimulus concentration, intraoral intake varied as a decreasing linear function of ingestion rate (infusion rate). In experiment II, a second (part B) infusion (0.5, 1.0, or 1.5 ml/min) was initiated 30 s after an initial (part A) infusion (0.5, 1.0, or 1.5 ml/min) of the same stimulus was rejected. Amount consumed during the part B infusion was substantial only when the part B infusion rate was lower than that of part A. Quantitative analysis of experiment II indicated that across sessions with common part B infusion rates, total session intake remained stable regardless of 1) whether the part A ingestion rate was greater than or equal to that of part B, 2) systematic differences in part A intake and duration, 3) differences in total session duration, and 4) differences in average ingestion rate for the session (total session intake/total session duration). The behavioral results are discussed in relation to the analysis of satiety under traditional intake testing paradigms and to gastric and postgastric theories of satiety. PMID- 2316714 TI - Triggering of erythropoietin production by hypoxia is inhibited by respiratory and metabolic acidosis. AB - Erythropoietin (EPO) production in response to hypoxic hypoxia is known to be attenuated by simultaneous hypercapnia. This study aimed to investigate whether this inhibitory effect of hypercapnia is 1) a direct effect of carbon dioxide or mediated by changes in pH or bicarbonate, 2) affects also carbon monoxide hypoxia, and 3) influences either the synthesis and release of EPO or the mechanisms by which hypoxia triggers an increase in EPO production rate. We found that EPO formation in mice exposed to normobaric hypoxia (8% O2) or to carbon monoxide (0.1%) was reduced by 30 and 42% when animals were simultaneously exposed to hypercapnia (7% CO2), by 35 and 38% when subjected to metabolic acidosis (NH4Cl), and unchanged when subjected to metabolic alkalosis (NaHCO3). In animals exposed to brief hypoxia (15 min) and subsequent normoxia (2 h), metabolic acidosis did not affect EPO levels when initiated after the hypoxic period. The results indicate that acidosis inhibits hypoxia-induced triggering of EPO formation independently of PCO2 and HCO3 levels. Because this inhibitory effect is also present during carbon monoxide hypoxia, it appears not solely due to potentiated hyperpnea. Alternatively, it may result from a facilitated intrarenal oxygen release or a direct effect at the EPO production sites. PMID- 2316715 TI - In vivo myocyte sodium activity and concentration during hemorrhagic shock. AB - The increase in intracellular Na+ concentration ([ Na+]i) and H2O content and decrease in K+ concentration during hemorrhagic shock have been observed. However, the state of the increased [Na+]i has never been defined. In this investigation double-barreled Na(+)-selective microelectrodes were used to directly measure in vivo intracellular Na+ activity (alpha Na) in skeletal muscle cells during prolonged hemorrhagic shock. Resting membrane potential, [Na+]i, and H2O content were also studied concomitantly. Sustained hemorrhagic shock with metabolic acidosis was produced in 12 rabbits after removal of approximately 40% of estimated blood volume under light anesthesia. During prolonged shock, resting membrane potentials of skeletal muscle cells depolarized to -74.7 +/- 1.7 mV from a base-line value of -92.6 +/- 0.4 mV. [Na+]i increased to 14.22 +/- 0.45 mmol/l from a base-line value of 11.50 +/- 0.32 mmol/l. Intracellular H2O content also had a 2.2% increase, whereas levels of [K+]i and extracellular H2O content decreased significantly. However, alpha i(Na) remained unchanged (4.07 +/- 0.19 mmol/l in base line and 4.04 +/- 0.20 mmol/l during shock). This makes the intracellular apparent activity coefficient for Na+ fall significantly from 0.356 in base line to 0.286 during shock. This result indicates that the extra Na+ that diffused into cell because of membrane dysfunction was bound to the fixed charges and/or compartmentalized into subcellular organelles. The unchanged alpha i(Na) also indicates that the depolarization of resting membrane potentials during sustained severe hypovolemia was not caused by the increased [Na+]i. The increase in extracellular [K+] during shock could account for the fall of the resting membrane potentials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316716 TI - Regulation of glycolysis in the pectoralis muscles of seasonally acclimatized American goldfinches exposed to cold. AB - Regulation of glycolysis was assessed in winter- and summer-acclimatized goldfinches (Carduelis tristis). We exposed birds to a thermo-neutral temperature (30 degrees C), moderate cold (-15 degrees C), and severe cold (0 degrees C in an atmosphere of 21% O2-79% He), and then measured concentrations of glycogen, glycolytic intermediates, and citrate in the pectoralis muscles. Winter birds used less glycogen when exposed to moderate cold than did summer birds, confirming the carbohydrate sparing noted by Marsh and Dawson [Am. J. Physiol. 242 (Regulatory Integrative Comp. Physiol. 11): R563-R569, 1982]. However, depletion of muscle glycogen did not correlate with thermoregulatory failure in this study. Concentrations of glucose 6-phosphate and fructose 6-phosphate in the pectoralis muscles were approximately 1.9 and 0.3 mumol/g wet mass in birds exposed to thermoneutral temperatures. The levels of these intermediates fell 50 70% under conditions known to enhance flux through glycolysis as indicated by increased glucose turnover and glycogen depletion. This information identifies phosphofructokinase (PFK) as a major regulated step in glycolysis in these highly aerobic skeletal muscles. Winter birds maintained the inhibition of this step under conditions of moderate cold. However, concentrations of citrate, which have been hypothesized to be an important inhibitor of PFK, did not correlate with the observed pattern of inhibition. Therefore, if the enhanced beta-oxidative capacity of winter birds is important in the regulation of glycolysis, a mechanism other than the accumulation of citrate may be involved. PMID- 2316718 TI - Measurements of core temperature in spontaneously hypertensive rats by radiotelemetry. AB - Spontaneously hypertensive (SH) rats have been shown to have elevated colonic temperatures when compared with normotensive Wistar-Kyoto (WKY) rats. In the present study, core temperatures of SH and WKY rats were compared using radiotelemetry temperature sensors implanted in the abdominal cavity. At an ambient temperature (Ta) of 25 degrees C, SH and WKY rats showed no significant difference in core temperature over a 24-h period. After 1 h exposures to Ta values of 5, 15, 25, or 35 degrees C, there were no significant differences between core temperatures of SH and WKY rats, but at 40 degrees C the SH rats had a significantly higher core temperature than the WKY rats. Handling and moderate restraint also led to significantly higher core temperatures in the SH rats. Core temperature was also significantly increased in the SH rats compared with the WKY rats when a temperature probe was either inserted intermittently or inserted and left in place. The results of this study indicate that nonstressed SH rats do not have an elevated core temperature but that stress such as heat exposure, handling, restraint, or even the presence of a colonic temperature probe can cause significant increases in core temperature in these rats. PMID- 2316717 TI - Suspension effects on rat femur-medial collateral ligament-tibia unit. AB - To study the influence of a 2-wk absence of normal weight-bearing forces on dense fibrous connective tissues of growing animals, the geometrical and biomechanical characteristics were examined of femur-medial collateral ligament (MCL)-tibia units (FMT unit) of age-matched controls and tail-suspended young male rats. During the 2-wk suspension, the rate of longitudinal growth of MCL decreased significantly, but no differences were found in the cross-sectional area of the MCL of the two groups. The tensile stiffness of suspension FMT units was significantly less than control, and the proportional, maximum, and failure loads of FMT units were also significantly less for the suspended animals. The stresses in the suspension MCL at the proportional limit were significantly less than control values. These results indicated that a 2-wk absence of normal weight bearing forces adversely affected the rate of longitudinal growth of MCL and the mechanical properties of the rat FMT unit. PMID- 2316719 TI - Decreased availability of metabolic fuels induces anestrus in golden hamsters. AB - Food deprivation inhibits ovulation and estrous behavior in golden hamsters. In experiment 1, the effects of phasic starvation (food deprivation on days 1 and 2 of the 4-day estrous cycle) depended on prior body weight and fat content. Starvation-induced anestrus, which occurs after only one cycle of phasic starvation in lean hamsters, did not occur until after three or more cycles in fat hamsters. None of the fat hamsters became anestrous until their body weights had declined to the level of lean hamsters. However, in experiment 2, we found evidence that changes in reproductive status were not signaled by any dimension of body size per se but instead by the general availability of metabolic fuels. Estrous cycles of thin hamsters were not significantly affected by food deprivation and weight loss when the hamsters were provided with either a 25% glucose solution or with vegetable shortening. In experiment 3, simultaneous pharmacological reduction of both fatty acid oxidation and glycolysis inhibited estrous cycles in hamsters fed ad libitum. Estradiol treatment restored estrous behavior, but not ovulation, in food-deprived, lean hamsters and in hamsters in which both fatty acid oxidation and glycolysis were reduced. Decreased availability of utilizable metabolic fuels may inhibit follicular development, which may in turn lead to circulating estradiol levels that are insufficient to stimulate estrous behavior. PMID- 2316720 TI - Mitochondrial and peroxisomal fatty acid oxidation in elasmobranchs. AB - In heart and red muscle of dogfish (Squalus acanthias), the maximal activities of the fatty acid catabolizing enzyme carnitine palmitoyltransferase (CPT) are less than 5% the rate in the same tissues of teleosts (carp, Cyprinus carpio; trout, Salmo gairdneri). CPT activities in these tissues of hagfish (Eptatretus stouti) are approximately 10% the rate in teleosts. However, the maximal activities of the beta-oxidation enzyme beta-hydroxyacyl-CoA dehydrogenase (HOAD) in dogfish red muscle and heart are similar to these tissues in the other species. This paradox prompted a more detailed study on the capacity of mitochondria from dogfish cardiac and red skeletal muscles to utilize fatty acids, possibly by a CPT-independent pathway. Free fatty acids were not oxidized by mitochondria from red muscle (hexanoate, octanoate, decanoate, and palmitate) or from heart (octanoate, palmitate). Neither hyposmotic incubation nor addition of 5 mM ATP could stimulate oxidation of octanoate or palmitate in either preparation, suggesting that these tissues have little capacity to oxidize fatty acids by a carnitine-independent pathway. Palmitoyl carnitine oxidation was detectable at very low rates in these mitochondria only with hyposmotic incubation. Octanoyl carnitine was oxidized at greater rates than palmitoyl carnitine, 10% the rate of pyruvate in both tissues, suggesting that medium-chain fatty acids could be physiologically relevant fuels in elasmobranchs if available to heart and red muscle. One potential source of medium-chain fatty acids is hepatic peroxisomal beta-oxidation, which occurs in dogfish liver at maximal activities similar to carp and trout liver. However, based on relative rates of oxidation, it is likely that dogfish heart and red muscle metabolism are fueled primarily by carbohydrate and ketone bodies. PMID- 2316721 TI - Training improves glucose homeostasis in rats during exercise via glucose production. AB - The effects of endurance training (running 1 h/day at 35 m/min, 10% grade) on glucose homeostasis during exercise (running 20 m/min) was studied in 30-h fasted rats. Primed-continuous infusion of [6-3H]- and [U-14C]glucose were employed to assess rates of appearance (Ra), disappearance (Rd), and apparent recycling. Training resulted in a 65% increase in skeletal muscle succinate dehydrogenase (SDH) activity but did not significantly influence body weight. Resting blood glucose concentrations were not significantly different between controls, 5.01 +/ 0.19 mM, and trained animals, 4.86 +/- 0.16 mM. Exercise resulted in a more rapid decline in blood glucose levels for control animals, reaching a value of 2.35 +/- 0.39 mM at 60 min, compared with 3.69 +/- 0.47 mM for trained animals. Glucose Ra was not significantly different between groups at rest, and rose for both groups during exercise. However, for controls Ra plateaued between 15 and 60 min of exercise at 11.03 +/- 0.73 mumol.100 g-1.min-1, whereas trained animals demonstrated a continuous rise to 17.13 +/- 1.18 mumol.100 g-1.min-1. Glucose Rd values were not significantly different between groups during the first 30 min of exercise but were significantly higher for trained animals during the final 30 min. As a result of the higher glucose Ra, trained animals demonstrated a smaller mean difference between Ra and Rd during exercise when compared with controls, 0.27 +/- 0.14 vs. -0.96 +/- 0.17 mumol.100 g-1.min-1. Trained animals further demonstrated significantly higher rates of glucose carbon recycling during the final 30 min of exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316722 TI - Angiotensin II binding sites in aortic endothelium of domestic fowl. AB - In domestic fowl, angiotensin II (ANG II) produces a unique vasodepressor response in vivo and endothelium-dependent relaxation of aortic rings in vitro that appear to be a direct effect on vascular smooth muscle mediated through vascular angiotensin receptors. To explore the possible role of the endothelium in ANG II-induced vasodilation, ANG II binding to aortic membrane fractions and intact endothelium and prostaglandin (PG) production were examined in fowl aortas. 125I-[Ile5]ANG II binding by endothelium-intact aortic membrane fractions was consistently higher than binding by identically prepared endothelium-deleted membrane fractions at virtually all concentrations of ligand (10 pM-0.20 microM). Incubation of intact aortic rings with 125I-[Ile5]ANG II (0.50 nM) resulted in specific endothelial binding that increased linearly with time from 5.5 +/- 1.7 (SE) fmol/mg protein at 5 min to 13.7 +/- 1.8 at 30 min. Endothelial ANG II binding increased linearly with the dose of ligand, from 2.7 +/- 0.3 fmol/mg protein at 0.1 nM to 21.0 +/- 2.2 at 1.0 nM. Specific ANG II binding to aortic endothelium was competitively displaced 73 +/- 11% by unlabeled ANG II (0.1 microM) but not by bradykinin (0.1 microM). Incubation of intact aortic rings with [14C]arachidonic acid resulted in the formation of radioactive metabolites that comigrated in thin-layer chromatography with authentic PGE2 but not with 6 keto-PGF1 alpha. PGE2 production by aortic rings (44.4 +/- 4.5 ng.mg dry tissue 1.h-1) was not stimulated by addition of ANG II. These results suggest that specific receptors for ANG II exist in fowl aortic endothelium and that PGs are not involved in ANG II-induced vasodilation of the fowl aorta. PMID- 2316723 TI - Cerebrospinal fluid pressure in conscious rats during prostaglandin E1 fever. AB - Intraperitoneal body temperature was monitored from groups of 10 conscious adult male Wistar rats. The daily body temperature rhythm was determined, and an intraperitoneal body temperature dose response relationship was established for prostaglandin E1 (PGE1) delivered into a lateral cerebral ventricle (LCV). Cerebrospinal fluid pressure was measured by direct cannulation of a LCV. Heart rate, arterial and central venous blood pressure, and blood gases were also measured in groups of 10 animals. It was found that there was a daily rhythm in intraperitoneal body temperature that was higher at night than during the day but stable between 0800 and 1600 h. A significant temperature dose (20-2,000 ng) response relationship was established for administration of PGE1 into the LCV. Cerebrospinal fluid pressure when measured from the LCV increased significantly during the "chill" phase of the PGE1-induced fever. Carotid arterial blood pressure also significantly increased at this time as did central venous pressure, particularly so with vigorous shivering. There was a significant fall in arterial CO2 partial pressure, a slight rise in pH, and no change in arterial O2 partial pressure. These data support the hypothesis that a significant increase in cerebrospinal fluid pressure occurs during the chill phase of a PGE1 induced fever in the conscious rat. PMID- 2316724 TI - Metabolic activation of efferent pathways from the rat area postrema. AB - We used the quantitative [14C]deoxyglucose method and autoradiography to evaluate metabolic activity in 47 individual cerebral structures or subregions that are part of neural pathways emanating from the brain stem circumventricular organ, area postrema. Electrical stimulation of the dorsocentral area postrema in halothane-ventilated rats produced hypotension and increased glucose metabolism by several structures within the ascending trajectories of efferent neural projections from the nucleus. Structures in the caudal medulla oblongata, including three subnuclei of the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and nucleus ambiguus-A1 noradrenergic region, had increases of metabolism during stimulation of 32-62%. Pontine activation occurred specifically in the locus coeruleus and lateral parabrachial nuclei (increases of 24-36%). Magnocellular and parvocellular subdivisions of the hypothalamic paraventricular nucleus, supraoptic and suprachiasmatic nuclei, and median eminence showed increases in metabolism of 22-34%. An 89% elevation of glucose metabolism by the pituitary neural lobe resulted. The findings are evidence for functional activation of specific structures within ascending neural pathways from area postrema to forebrain mechanisms regulating blood pressure and fluid balance. PMID- 2316725 TI - Role of interleukin 6 in fever in rats. AB - The purpose of these studies was to assess whether interleukin 6 (IL-6) is an endogenous pyrogen, responsible for all or part of the fever caused by lipopolysaccharide (LPS) in rats. We have found that the core temperature (as measured by biotelemetry) rose significantly after intracerebroventricular (icv) injection of recombinant human IL-6. The same doses of IL-6, when administered intravenously or intraperitoneally, had no effect on body temperature. The fever caused by icv administration of IL-6 was completely blocked by indomethacin. After injection of fever-inducing doses of LPS, the plasma and cerebrospinal fluid (CSF) IL-6 activities rose, the former much more than the latter. The correlation between fever and plasma IL-6 activity was r = 0.84 (P less than 0.0025); the correlation between fever and CSF IL-6 activity was r = 0.77 (P less than 0.015). The results of this study are consistent with the hypothesis that IL 6 is a mediator of LPS-induced fever in the rat. PMID- 2316726 TI - Deuterium and oxygen-18 abundance in birds: implications for DLW energetics studies. AB - The doubly labeled water (DLW) technique for measuring energy expenditure may employ one (18O) or two (18O and deuterium) stable isotopes as tracers. These occur naturally in the environment, so when they are used as tracers it is necessary to subtract the background levels. Few studies report data on background concentrations. This work provides such data for a range of avian species. Overall, there was a strong positive correlation (r = 0.63) between the 18O and deuterium concentrations in birds' body water. Variation in the deuterium concentration was less extensive than in the 18O concentration (1:2.7 parts/million). In the European robin, there was a linked, seasonal variation in 18O and deuterium abundance producing high summer and low winter values. Throughout the year, a high individual variability was greater in 18O than in deuterium. A difference between the European robin and the dipper suggests that habitat may also influence background abundance. Investigation of the effect of variation in background abundance on measures of energy expenditure for small passerines (20 g) revealed that employing estimates, instead of direct measurements, had a minor influence over an experimental period of 1 day but could potentially introduce errors as large as 54% over a 2-day period. PMID- 2316727 TI - Light and target distance interact to control pupil size. AB - Light and target distance stimuli were presented to normal human subjects, and their pupillary responses were measured. A homeomorphic computer model of the pupillary control system is presented in which the form of interaction of controller signals due to light and target distance was investigated. The error remaining when model parameters were optimized to fit experimental pupil size (area or diameter) was smaller for the linear interaction hypothesis than for either power law or logical law interaction. A generalized second-order nonlinear model with six parameters (vs. 3 for each of the other models) yielded somewhat lower residual error. With the use of a modified Akaike information criterion, the value (in an information theoretic sense) of the improved fit afforded by the three additional parameters in the generalized nonlinear model was shown to be small, and thus the generalized second-order nonlinear model was rejected in favor of the simpler and more parsimonious linear model. PMID- 2316728 TI - Chemospecific deficits in taste detection after selective gustatory deafferentation in rats. AB - Electrophysiological data support the existence of sodium-specific taste receptors that appear to be limited to the anterior tongue. However, previous behavioral findings suggest that bilateral transection of the chorda tympani nerve (CTn) has minimal consequences on NaCl intake and preference. This study employed a conditioned avoidance procedure to measure detection thresholds to NaCl and sucrose both before and after bilateral transection of the CTn. Rats were trained to maintain spout contact in response to water presentations (70 microliters) and to avoid spout contact when a taste solution (70 microliters) was presented. In experiment 1, all rats (n = 3) showed statistically significant impairments in the detectability of NaCl after bilateral section of the CTn. The mean increase in the NaCl detection threshold was 1.41 log units. In contrast, sucrose threshold in these same rats was marginally affected by CTn section (mean increase = 0.22 log units). Experiment 2 (n = 4) replicated the findings of the first experiment. The mean increase in the NaCl detection threshold was 2.23 log units. Sucrose threshold in these rats was, again, only marginally affected by CTn section (mean increase = 0.83 log units). Histological examination of the anterior tongue from the rats in experiment 2 indicated that the CTn transections were complete. These findings reveal that the anterior oral receptive field (innervated by the CTn) containing only 15% of the total taste bud population is critical for the normal detection of NaCl. PMID- 2316729 TI - Whatever happened to intensive psychotherapy? AB - Of 163 residency programs responding to a survey about training requirements in long-term psychotherapy, more than 100 did not require that any patients be seen more than once a week. Among 41 psychotherapy protocols representing outcome related research that were reported at an annual meeting of the Society for Psychotherapy Research, the studies employing more than once-a-week treatment for 6 or more months were rare. Intensive psychotherapy is clearly on the wane in training programs and in psychotherapy research paradigms. PMID- 2316730 TI - Progression of illness in the differential diagnosis of primary dementia. AB - The diagnostic utility of determinations of insidious or stepwise progression of illness was examined in 124 geriatric inpatients with primary dementia. Such determinations failed to distinguish patients with primary degenerative dementia of the Alzheimer type from those with multi-infarct dementia. Episodic behavioral complications, especially depression and delusions, in the patients with primary degenerative dementia were associated with stepwise progression. Determinations of stepwise progression were made in only six (15%) of the 40 demented patients with at least two cerebral infarctions, a finding inconsistent with current diagnostic criteria for multi-infarct dementia. PMID- 2316731 TI - Association between family history of affective disorder and the depressive syndrome of Alzheimer's disease. AB - For each of 41 index patients with probable Alzheimer's disease and a first episode of major depression and 71 nondepressed Alzheimer's disease patients, two first-degree relatives were interviewed by a rater blind to presence or absence of depression in the proband. The depressed patients had significantly more first and second-degree relatives with depression than did control subjects. The lifetime risk for major depression, adjusted for differences in age distribution, was significantly greater in first-degree relatives of index patients, suggesting that depression in Alzheimer's disease is genetically related to primary affective disorder. Alzheimer's disease may be useful for studying aspects of depressive pathophysiology. PMID- 2316732 TI - Plasma concentrations of melatonin in panic disorder. AB - Nocturnal plasma melatonin concentrations were measured in seven patients with panic disorder and eight healthy control subjects. The five patients who had never received psychotropic medication had significantly greater melatonin concentrations from 4:00 a.m. to 7:00 a.m. than the control subjects. In addition it is possible that a phase delay occurred in these unmedicated patients. The findings are discussed in terms of previous studies showing increased melatonin in manic patients and the effect of intense stress on melatonin synthesis. The two patients who had been medication free for only 1 week showed a decreased melatonin rhythm, which is consistent with previous findings in medicated patients. PMID- 2316733 TI - Relationship between utilization of mental health and medical services in a VA hospital. AB - Previous research has demonstrated a reduction in utilization of medical services following the initiation of psychiatric services for certain patients. The phenomenon has been called the offset effect. The authors investigated the offset effect in a Veterans Administration medical center setting. They found that the offset effect emerged only for patients who had high rates of use of medical services who received mental health services for 1 year or less. They discuss factors related to higher rates of medical care utilization as well as important differences between the present and previous research that require further study. PMID- 2316734 TI - The borderline diagnosis in adolescents: symptoms and developmental history. AB - Adult criteria for borderline personality disorder distinguished a group of 27 inpatient adolescent girls from 23 nonborderline inpatient female comparison subjects. The two groups were compared on retrospectively assessed variables measuring psychological, familial, and constitutional factors. Variables most likely to predict borderline personality disorder included history of disrupted attachments, maternal neglect, maternal rejection, grossly inappropriate parental behavior, number of mother and father surrogates, physical abuse, and sexual abuse. Families of borderline adolescents were chronically disrupted, particularly during the patients' early childhoods. The traumatic childhood experiences of the borderline adolescents were similar to those of adults with borderline personality disorder in recent studies. PMID- 2316735 TI - Glucose tolerance testing in women with premenstrual syndrome. AB - Glucose tolerance tests (GTTs) were administered to 11 women with premenstrual syndrome (PMS) to ascertain whether the patients had abnormalities of glucose tolerance, to determine whether such abnormalities were related to menstrual cycle phase, and to compare the symptoms during the GTT with the PMS symptoms experienced in the luteal phase. Two GTTs were performed for each patient, one during the late follicular phase and one during the late luteal phase. Although many patients experienced symptoms of hypoglycemia during the GTT, the hypoglycemia symptoms were not specific to the luteal phase and did not resemble the patients' PMS symptoms. PMID- 2316736 TI - Tridimensional Personality Questionnaire scores of sons of alcoholic and nonalcoholic fathers. AB - The authors studied 33 men whose fathers had severe alcohol-related problems and 33 subjects with no family history of alcoholism. The former supplied information about the course of their fathers' alcohol problems; all 66 men answered questions about their own drinking and drug use and completed the Tridimensional Personality Questionnaire. There were no significant relationships between any of the 18 questionnaire scores and a subject's quantity/frequency of drinking or his family history of alcoholism. There was only one significant correlation between the alcoholic fathers' type 2 characteristics, according to the type 1/type 2 theory, and the sons' questionnaire scores. The relevance of these findings to the theory is discussed. PMID- 2316737 TI - Paradoxical patient reactions to psychiatric life support: clinical and ethical considerations. AB - The authors describe cases illustrating two types of high-risk and especially difficult suicidal psychiatric inpatients. In the first case, a suicidal patient reacted to psychiatric life support measures (maximum observation) with increasingly life-threatening acting out, necessitating a difficult, seemingly paradoxical staff decision to withdraw life support. In the second, a patient felt to be improving killed herself when life support was withdrawn. The authors argue that there are clinical limits to psychiatric life support and an appropriate goal of psychiatric treatment is to maximize the chances for patient survival, rather than to attempt to guarantee such survival. PMID- 2316738 TI - Reliability of categorical and dimensional judgments of personality disorder. AB - To investigate interrater reliability on categorical and dimensional judgments of personality disorder, five clinicians completed five different judgment tasks for each of 10 case vignettes. The reliability estimates support previously unconfirmed statements that dimensional judgments are substantially more reliable than categorical diagnoses. PMID- 2316739 TI - Effects of methylphenidate on early adolescent growth. AB - Thirty-one hyperactive adolescents treated with methylphenidate for at least 6 months demonstrated no significant deviation from expected height and weight growth velocities. In contrast to findings in prepubertal children, these results suggest that early adolescent growth is insensitive to methylphenidate. PMID- 2316740 TI - Weight gain associated with clozapine. AB - Six of seven patients treated with clozapine gained 6-69 lb. Because of clozapine's anticipated availability in the United States, clinicians should be aware of this possible side effect, which, to the authors' knowledge, has not been reported previously. PMID- 2316742 TI - Effect of distraction on communication failures in schizophrenic patients. AB - Manic, schizophrenic, and normal subjects were interviewed in the presence and absence of distracting information, and their speech performance was evaluated. Normal and manic subjects were unaffected by irrelevant information. Schizophrenic subjects manifested more reference failures during distraction than during nondistraction periods. PMID- 2316741 TI - Evidence for physical and psychological dependence on anabolic androgenic steroids in eight weight lifters. AB - All eight users of anabolic androgenic steroids in a pilot survey of weight lifters reported withdrawal symptoms and continued steroid use despite adverse consequences. Psychiatric (especially, depressive) symptoms were prominent in dependent users, underscoring the importance of diagnosing steroid dependence in clinical practice. PMID- 2316743 TI - Overcoming hypersensitivity to fluoxetine in a patient with panic disorder. PMID- 2316744 TI - MAOIs and Meniere's syndrome. PMID- 2316746 TI - Schizotypal personality and brief reactive psychosis. PMID- 2316745 TI - Propranolol withdrawal in psychosis. PMID- 2316747 TI - Tarasoff and threats of patricide by a 9-year-old boy. PMID- 2316749 TI - Seasonal birthrates and schizophrenia. PMID- 2316748 TI - Long-term follow-up of a patient who received electrical stimulation for chronic vomiting. PMID- 2316750 TI - Psychobiology and the brain-mind relationship. PMID- 2316751 TI - Importance of consultation-liaison psychiatry. PMID- 2316753 TI - Photophobia in other disorders as well as depression. PMID- 2316752 TI - Multiple personality disorder: the new "royal road"? PMID- 2316754 TI - Role of psychotherapy in bipolar disorder. PMID- 2316755 TI - P.T. Barnum and the borderline personality disorder muddle. PMID- 2316756 TI - Editor's report: scientific misconduct and the responsibility of journal editors. PMID- 2316757 TI - Stalking the HIV epidemic: which tracks to follow and how far? PMID- 2316758 TI - When is the quality of care good enough? PMID- 2316759 TI - Human immunodeficiency virus seropositivity among members of the active duty US Army 1985-89. AB - Between October 1985 and June 1989, most active duty US Army soldiers were screened for human immunodeficiency virus (HIV) antibody. Of 648,032 screened soldiers in this analysis, 1,588 were HIV-antibody positive. In a multivariate analysis, correlates of positivity included: age [Adjusted Odds Ratios (ref less than 20 years) = 20-24 years, 3.7; 25-29, 9.3; 30-34, 15.7; greater than or equal to 35, 15.9]; being male, [4.2]; being Black or Hispanic (vs white) [3.7 and 3.0, respectively]; being single (vs married) [3.8]; assignment to an HIV endemic location [1.7], and having a medical occupation [2.7, 2.7, and 2.6 for negligible, low, and high blood exposure professions, respectively]. Seropositivity rate ratios for medical vs non-medical personnel were 0.7 [95% CI = 0.4, 1.4] for females and 2.9 [95% CI = 2.5, 3.3] for males. For male medical personnel, being single (vs married) correlated strongly with antibody positivity [prevalence ratio = 3.4, 95% CI = 2.6, 4.6]. Excess HIV risk among medical personnel appeared largely attributable to factors other than occupational exposures. PMID- 2316760 TI - AIDS risk behavior patterns among gay men in small southern cities. AB - Men entering gay bars in three small southern cities were administered questionnaires to assess AIDS (acquired immunodeficiency syndrome) risk knowledge, perceived norms concerning the social acceptability of AIDS risk precautions, and personal sexual behavior. Seventy-seven percent (N = 355) of male patrons completed the measures. While risk knowledge levels were high, respondents did not perceive strong norms favoring risk reduction precautions. Rates of risk behavior were considerably higher than those reported for gay men in large urban epicenters. PMID- 2316761 TI - HIV-1 counseling and testing sites, Minnesota: analysis of trends in client characteristics. AB - We report here a summary of the data obtained from two HIV-1 antibody counseling and testing sites in Minneapolis-St. Paul for the first 48 months of operation (24,911 persons tested). The HIV-1 antibody seroprevalence rate for all persons tested was 5 percent. The highest seroprevalence rates were in male homosexual/bisexual intravenous drug users (23 percent) and homosexual/bisexual men (13 percent). There was a significant decrease in the HIV-1 antibody seroprevalence rate among clients during the 48-month period from 14 percent in the first six months to 3 percent in the last six months. This decrease coincided with an increase in the number of low-risk female clients and low-risk heterosexual male clients, and a decrease in the number of homosexual/bisexual males participating in the programs. These findings suggest the need for development and implementation of other strategies to identify and reach persons at highest risk for HIV-1 infection. PMID- 2316762 TI - Potential for laboratory exposures to biohazardous agents found in blood. AB - The magnitude of risk for occupational exposures to biohazardous agents found in blood was assessed by 800 environmental samples taken from a total of 10 clinical and research laboratories at the National Institutes of Health (NIH). Thirty-one samples from 11 work stations in three laboratories contained hepatitis B virus surface antigen (HBsAg). Observations of workers indicated that environmental contamination arose from several sources. Among the 11 work stations with HBsAg environmental samples, eight had high work loads, seven had inappropriate behaviors, and nine had flawed laboratory techniques. This information suggests that a multifactorial approach is needed to minimize the risk of laboratory associated infections. PMID- 2316764 TI - Tuberculin skin testing in US Navy and Marine Corps personnel and recruits, 1980 86. AB - An extensive skin testing program is part of the United States Naval Medical Command's infectious disease control effort. From 1980 to 1986, 2,306,533 skin tests, using five TU PPD, were performed on active-duty Navy and Marine Corps personnel, 0.97 percent of which were positive. A downward trend in positive tests was found with a high of 1.43 percent in 1980 and a low of 0.80 percent in 1983. Since 1984, the percentage of positive tests has remained the same or increased. Shore-based medical facilities around the world reported 1,491,646 skin tests with 1.07 percent positive; Navy ships reported 814,887 skin tests with 0.78 percent positive. PPD-positivity for ships in the Pacific area was higher (0.98 percent) than for ships in the Atlantic (0.62 percent). During this same period, the percentage of positive tests in Navy and Marine Corps recruits ranged from a high of 1.82 percent in 1981 to a low of 1.23 percent in 1986. Since 1984, the percentage of positive tests has remained relatively stable in recruits. The frequency of positive PPD tests found in this study is lower than the percentage positive (1.59 percent) found in active-duty Navy personnel in 1969 and the percentage positive (5.2 percent) found in a study of Navy and Marine Corps recruits between 1958 and 1969. PMID- 2316763 TI - A rural outbreak of Legionnaires' disease linked to visiting a retail store. AB - Between May 7 and June 7, 1986, 27 residents of a rural county in Maryland developed legionellosis, and two died. Legionella pneumophila serogroup 1 was cultured from the sputum of two patients and identified in lung tissue of a third patient by direct fluorescent antibody staining. An additional 11 patients had four-fold rises in antibody titer to L. pneumophila, and 13 had single titers greater than or equal to 1:256. To determine risk factors for disease, we performed a case-control study. Twelve of 16 case-patients reported visiting store A in the two weeks before onset of illness compared with four of 28 control patients. A serologic survey of employees showed that employees of store A were 3.63 times more likely than control employees to have titers of antibody to L. pneumophila greater than or equal to 1:256 (95% confidence intervals 0.8, 16.7). Cultures of soil specimens, samples of water from the hot water system of store A and from stagnant ponds near store A collected five weeks after the end of the outbreak were negative for Legionella species. Store A was adjacent to a site of excavation and construction during May 1986, when the community was experiencing an extended drought. This investigation suggests that exposure to excavation and construction activity may be a risk factor for legionellosis. PMID- 2316765 TI - Tuberculosis infection in urban adolescents: results of a school-based testing program. AB - In 1986-87 a pilot tuberculosis (TB) skin testing program was introduced for seventh and tenth grade students in the Boston (Massachusetts) public schools. The 8.9 percent tuberculin positivity rate in tenth grade students was significantly higher than the 5.1 percent rate found in seventh graders. A majority of those who were skin test positive were born outside the United States. These results suggest that tuberculin testing in an urban school setting may identify a significant number of candidates for TB preventive therapy, particularly among tenth grade students and those who are foreign-born. PMID- 2316766 TI - Epidemiologic and clinical characteristics of persons with serologic evidence of E. canis infection. AB - The results of a serosurvey of Oklahomans for the presence of antibody to Ehrlichia canis is reported. Paired serum specimens, from patients lacking the serologic criteria for diagnosis of Rocky Mountain spotted fever (RMSF), were tested. A four-fold increase in E. canis-IFA antibody was found in 16/144 (11 percent) of these paired serum samples. Patients with serologic evidence of E. canis infection had a mean age of 34 years, 69 percent were male, and 63 percent lived in a town less than 10,000 population. Signs and symptoms included: fever 94 percent, headache 94 percent, fatigue 94 percent, anorexia 81 percent, nausea 60 percent, and rash 44 percent. When compared to control patients, whose sera were submitted for RMSF testing but did not meet serologic criteria for RMSF or E. canis, case-patients were more likely to have had leukopenia (OR = 4.9, 95 percent Cl = 1.2, 19.0) and tick exposure (OR = 9.5, 95 percent Cl = 1.4, 62.7). The results suggest E. canis, or a closely related agent, is a cause of human illness. Ticks are probable vector. PMID- 2316767 TI - Self-rated health and mortality in the NHANES-I Epidemiologic Follow-up Study. AB - The ability of self-rated health status to predict mortality was tested with data from the National Health and Nutrition Examination Survey (NHANES-I) Epidemiologic Follow-Up Study (NHEFS), conducted from 1971-84. The sample consists of adult NHANES-I respondents ages 25-74 years (N = 6,440) for whom data from a comprehensive physical examination at the initial interview and survival status at follow-up are available. Self-rated health consists of the response to the single item, "Would you say your health in general is excellent, very good, good, fair, or poor?" Proportional hazards analyses indicated that, net of its association with medical diagnoses given in the physical examination, demographic factors, and health related behaviors, self-rated health at Time 1 is associated with mortality over the 12-year follow-up period among middle-aged males, but not among elderly males or females of any age. PMID- 2316768 TI - HIV prevention: the need for methods women can use. AB - Efforts to prevent heterosexual transmission of HIV (human immunodeficiency virus) infection have thus far focused on modifying sexual behaviors and the use of condoms. While the experience of family planners, particularly in those countries most threatened by heterosexual HIV transmission, has shown that the most effective measures of pregnancy prevention have relied on women, little attention has been given to barriers to HIV transmission that depend on the woman and are under her control. Tactics which interrupt transmission of the virus should be considered in their own right and separated from those that interrupt pregnancy, for insurance, the diaphragm. Greater emphasis is urged for research on preventive methods women could use, including the possibility of a topical virucide that might block transmission through the vaginal route. PMID- 2316769 TI - Evaluation of active versus passive AIDS surveillance in Oregon. AB - We searched for unreported AIDS cases in Oregon through death certificate and medical record review, and enhanced infection control practitioner and physician surveillance. Fifty-six AIDS cases diagnosed between February 1, 1986 and January 31, 1987 were reported passively. Twenty-nine additional cases diagnosed during this time were retrospectively identified by active methods. Ninety percent of those 29 cases were diagnosed by physicians and cared for in hospitals that had previously reported cases. Completeness of reporting under the passive system was 64 percent. PMID- 2316770 TI - The prevalence of high-risk sexual behavior in male intravenous drug users with steady female partners. AB - A sample of 149 (70 White, 79 Black) male intravenous drug users with steady female sexual partners was interviewed in 1987, in treatment and street settings, about sexual practices during the previous five years. Eighty-three percent had multiple partners, 15 percent reported male sexual contact, 38 percent reported heterosexual anal intercourse, and 73 percent never used condoms. Thirty-seven White and 30 Black subjects reported bisexuality or heterosexual and intercourse or both. PMID- 2316771 TI - Are patients talking to their physicians about AIDS? AB - We conducted a nationwide telephone survey of a random sample of United States adults in summer 1988 (n = 2000, response rate = 75 percent) to find out if physicians were providing education and counseling to the public about AIDS and AIDS prevention. Within the previous five years, 94 percent had seen a physician but only 15 percent had discussed AIDS even though most said they would not object to discussing the topic. AIDS-related conversations are not commonplace in physician's offices and in most cases (72 percent) patients are the initiators of such conversations. PMID- 2316772 TI - Prevalence of markers for hepatitis B and hepatitis D in a municipal house of correction. AB - Following an outbreak of hepatitis B (HBV) in a municipal house of correction, HBV markers were detected in 173/406 (43 percent) inmates and 10/129 (8 percent) staff. Of the 173 HBV-infected inmates, 14 (8 percent) had hepatitis D (HDV) markers compared to 0/10 staff members. Intravenous drugs use (IVDU) was most strongly associated with HBV marker presence. Increasing duration of imprisonment, history of hepatitis B and especially IVDU were associated with the prevalence of HDV markers. PMID- 2316773 TI - Influenza epidemics and anencephaly. AB - To explore the postulated association between maternal influenza and congenital defects of the central nervous system, 14 virologically verified epidemics in Finland, 1969-82, were studied. Mothers of 248 anencephalic children were grouped into those whose first trimester had occurred during an epidemic period and those whose pregnancy had commenced during a non-epidemic period. No significant differences in prevalence of anencephaly were noted in these groups. PMID- 2316775 TI - Health effects of a thorium waste disposal site. AB - A case-control study of 112 households residing in the vicinity of a thorium waste disposal site found a higher prevalence of birth defects (RR 2.1) and liver diseases (RR 2.3) among exposed than the unexposed group. The numbers were quite small and the confidence intervals wide, however, so that no definite conclusions can be drawn from these data. PMID- 2316776 TI - Comparison of antineoplastic drug handling policies of hospitals with OSHA guidelines: a pilot study. AB - Hospital antineoplastic drug handling policies of 24 hospitals in eight Southwestern Ohio counties were compared with recommendations of the 1986 Occupational Safety and Health Administration (OSHA) guidelines. Although most study facilities where antineoplastics are handled have policies, content varies and is generally less complete than OSHA guidelines, particularly regarding storing, transporting, and disposing of drugs; managing equipment; informing personnel of risk; and surveillance. Recommendations for personal protection concur more closely with OSHA guidelines than do other content areas. PMID- 2316774 TI - Rabies Vaccine Adsorbed: neutralizing antibody titers after three-dose pre exposure vaccination. AB - Field trials at several schools of veterinary medicine showed that three-dose pre exposure rabies vaccination with Rabies Vaccine Adsorbed developed by the Michigan Department of Health elicited neutralization antibody in practically all recipients two to three weeks after immunization. Titers declined during the first six months after vaccination. However, by 18 to 24 months, 98 percent of recipients still had titers equal or greater than a 1:5 dilution of serum. PMID- 2316778 TI - The female condom. PMID- 2316777 TI - Trends in hospital utilization, 1965-86. PMID- 2316779 TI - Personality traits and addictive disease. PMID- 2316780 TI - AIDS as a cause of death in children, adolescents, and young adults. PMID- 2316781 TI - Lifetime risk of a hip fracture. PMID- 2316782 TI - The onset of decline in ischemic heart disease in Italy. PMID- 2316783 TI - Dirofilaria striata infection in a North Carolina child. AB - A living, adult female Dirofilaria striata was removed from the orbit of a 6-year old boy living in Buncombe County, NC. The specific identification of the filaria was based on its size and the morphological features of the cuticle including the weak, irregular, longitudinal ridges and small but conspicuous lateral alae. PMID- 2316784 TI - Cryptosporidiosis: a cause of diarrhea in Bangladesh. AB - Fecal samples from diarrheal patients and non-diarrheal controls were examined for Cryptosporidium oocysts in a year-long prospective study at a diarrhea treatment center in Dhaka, Bangladesh. Cryptosporidium oocysts were detected in 42 (3%) of 1,382 diarrheal patients but in none of 235 non-diarrheal controls. In 32 (76%) of 42 patients, no other enteropathogens were detected. Children less than 5 years of age were more commonly infected than older children (4.8% vs. 1.6%, P greater than 0.05) and adults (4.8% vs. 0.2%, P less than 0.01). A higher number of cases were detected during hot and humid months (April--July). Nineteen children less than 5 years of age (index cases) and their 71 family members were followed for 3 weeks after the release of the index cases from the hospital. Diarrhea continued for greater than 14 days (persistent diarrhea) in 8 (32%) index children. Cryptosporidium oocysts were detected in 1 (12.5%) of 8 family members who developed diarrhea during the follow-up period. Index cases excreted oocysts for 3-28 days (12.37 +/- 8.35 days). Almost all the patients recovered with oral rehydration. Cryptosporidium ssp. cause self-limited diarrhea episodes in children less than 5 years of age in Bangladesh, with a low frequency of intrafamilial transmission. PMID- 2316786 TI - Effect of mass treatment of a human population with ivermectin on transmission of Onchocerca volvulus by Simulium yahense in Liberia, West Africa. AB - The impact of mass treatment with ivermectin on the intensity of Onchocerca volvulus transmission by the black fly (Simulium yahense) was evaluated on the Liberian Agricultural Company rubber plantation in Liberia, West Africa. The adult pre-treatment prevalence of onchocerciasis was greater than 80%, and the average intensity of infection was 5.35 mf/mg of skin. The drug was administered at 2 annual intervals, reaching 58-60% of the approximately 14,000 people living in 73 camps. Landing/biting catches of black flies made in central and peripheral plantation zones indicated similar fly activity before and after ivermectin treatment (man hr index of 2.1 and 2.4 within the plantation, and 10 and 10.9 outside the plantation, respectively). The number of infected flies with developing larvae (L1, L2, L3 stages) of O. volvulus in treated areas was reduced by 93.4-95%; the number of infective flies with L3 larvae was reduced by 81.7 89.3%. Parasite loads of infected (L1, L2) and infective flies (L3 stages only) outside the plantation also decreased by 86.8% and 80%, respectively. Monthly transmission potential (MTP) showed a similar decrease: from 22.9 to 5.8 (74.6% reduction) in the treated area, and from 210 to 158.8 (24.4% reduction) in untreated areas. Mass treatment with ivermectin efficiently controlled, and at least temporarily interrupted, transmission of Onchocerca volvulus by black fly vectors. PMID- 2316785 TI - Immune response to cryptosporidiosis in Philippine children. AB - An ELISA was used to measure the Cryptosporidium-specific IgA, IgG, and IgM antibody levels in serum, stool, and duodenal fluid of 15 Filipino children. Antibody levels were measured on admission to the hospital, 1 week later, and at a 6 week follow-up examination. Delayed type hypersensitivity skin tests were used to assay cell mediated immunity (CMI), iron status was measured by serum iron tests and total iron binding capacity, and the degree of malnutrition was determined by clinical examination. Antibody response to Cryptosporidium was qualitatively and quantitatively strong and maintained over time. All subjects showed impaired CMI early with some reconstitution after 6 weeks. All subjects showed some degree of malnutrition and/or depleted iron status. PMID- 2316787 TI - Equine rabies immune globulin: a product with an undeserved poor reputation. AB - Four hundred nineteen patients exposed to rabies in Thailand were treated with equine rabies immune globulin (ERIG) manufactured by Sclavo of Italy, a product also licensed in the United States of America. They were followed for a minimum of 1 month after ERIG injection and rabies vaccine administration. Adverse serum sickness-like reactions were noted in 15 patients (3.58%). These were clinically acceptable and only 1 of these patients required corticosteroid therapy and short term hospitalization for serum sickness. ERIG is approximately 1/10 of the cost of human rabies immune globulin (HRIG), which is not generally available in developing countries. ERIG is a safe and underutilized essential biological when HRIG is not affordable or available. PMID- 2316789 TI - Transmission of Rift Valley fever virus by the sand fly, Phlebotomus duboscqi (Diptera: Psychodidae). AB - Studies were conducted to determine if the sand fly Phlebotomus duboscqi could serve as a vector of Rift Valley fever (RVF) virus. When 145 P. duboscqi were fed on a hamster with RVF viremia (approximately 10(9) PFU/ml of blood), 72 (50%) became infected. Of 5 with disseminated infections (i.e., virus recovered from their legs) 4 transmitted virus to hamsters by bite. Sand flies were uniformly infected when RVF virus was inoculated by the intrathoracic route, and each of 31 sand flies so inoculated that fed on a hamster transmitted virus. None of 331 progeny of inoculated sand flies or 230 progeny of orally exposed sand flies contained virus. Sand flies could serve as vectors of RVF virus. PMID- 2316790 TI - Distribution and etiology of leishmaniasis in Colombia. AB - A total of 340 Leishmania strains, isolated from humans, animals, and sand flies from various regions of Colombia, were examined by isozyme electrophoresis. Seven different Leishmania species were identified. Leishmania panamensis and L. braziliensis were the most common, representing 53.8% and 30.3% of the total, respectively. Isolation rates of the other species were as follows: L. chagasi, 9.4%; L. guyanensis, 2.6%; L. amazonensis, 1.8%; L. mexicana, 0.8%; and a new species requiring additional study, 1.2%. Statistical analyses of representative L. panamensis and L. braziliensis isolates indicated that the populations of these 2 species are genetically very similar. L. panamensis may have a continuous distribution in Colombia west of the eastern Andes Mountains and L. braziliensis may have a continuous distribution east of the western Andes Mountains. Information is given on disease manifestations of the parasites in human hosts and on isolation records from sand flies and animals. PMID- 2316788 TI - Dengue hemorrhagic fever in Cuba, 1981: a retrospective seroepidemiologic study. AB - In Cuba, 2 epidemics of dengue virus occurred: 1 caused by DEN-1 in 1977 and 1 caused by DEN-2 in 1981. The latter was associated with cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). To study viral risk factors for DHF/DSS, a retrospective seroepidemiological survey was conducted in Cerro, a densely populated district in Havana City. The prevalence of plaque reduction neutralizing antibodies to DEN-1 and DEN-2 viruses was measured in 1,295 individuals (children and adults). Of these, 43.7% were immune to DEN-1 virus and 23.6% to DEN-2 virus. Of those individuals who were immune, 26.1% were immune to DEN-1 virus only, 6% to DEN-2 virus only, and 17.6% to both viruses. The DEN-2 virus infection rate in DEN-1 immune individuals was 3.8 times higher than in non immune individuals. The 5 DHF/DSS cases in the sample had evidence of DEN-1 virus plus DEN-2 virus infections. Three were children and 2 were young adults. No cases were found in individuals infected with DEN-1 virus or DEN-2 virus only. Children infected by DEN-1 virus followed by DEN-2 virus had a high risk of acquiring DHF/DSS. Blacks and whites were equally infected with DEN-1 and DEN-2 viruses. PMID- 2316791 TI - An epidemic of Oroya fever in the Peruvian Andes. AB - Between February and October 1987, a febrile illness killed 14 persons and seriously affected at least 14 others in Shumpillan, a remote Peruvian mountain village of 353 people. The illness was characterized by fever, headache, chills, and pallor. The fatality rate of untreated cases was 88%. The patients, 71% of whom were male, were 1-75 years of age. Fatal illnesses progressed from lethargy to coma to death in 3-60 days. Patients treated empirically with chloramphenicol survived. Bartonella bacilliformis was isolated from the whole blood of 3 patients. A serologic study revealed a high prevalence of antibodies to B. bacilliformis in the villagers. It is concluded that the villagers suffered from an epidemic of Oroya fever. PMID- 2316793 TI - A survey of the intestinal nematodes of Bushmen in Namibia. AB - Studies in Namibia revealed prevalence rates of 63% for hookworm and 35% for Trichuris in 31 Bushmen, 4-65 years of age, who were encamped in the Kaudom Game Reserve. The study also revealed prevalence rates of 85% for hookworm, 25% for Strongyloides, and 1% for Trichuris in 103 children, 6-17 years of age, attending 5 schools in Bushmanland. The 25% Strongyloides infection rate is one of the highest prevalences recorded in southern Africa. The Trichuris infections in the Kaudom group appeared to be autochthonous, and this population did not harbor Strongyloides. Regular contact with pans in summer and boreholes at any time probably facilitated the acquisition of infections in wet and fecally polluted sites. Thirteen spurious Physaloptera infections were recorded. PMID- 2316792 TI - Ultrastructural studies on the effect of tumor necrosis factor on the interaction of neutrophils and Naegleria fowleri. AB - Naegleria fowleri is the common etiologic agent of primary amebic meningoencephalitis (PAM). We investigated the interaction of human neutrophils with Naegleria trophozoites and examined the effect of neutrophil stimulation by the recombinant human tumor necrosis factor (TNF) on this interaction. As indicated by scanning and transmission electron microscopy, TNF stimulated the adherence of neutrophils to N. fowleri with destruction of the ameba. Neutrophil iodination, an indirect measure of stimulation, increased from 0.81 +/- 0.23 nmol/10(7) cells/hr to 2.41 +/- 0.62 nmol/10(7) cells/hr following the addition of TNF to the neutrophil-N. fowleri mixture (P less than 0.05). This was independent of complement or specific immunoglobulin. Ingestion of neutrophils by Naegleria trophozoites was observed following more prolonged incubation, particularly in the absence of TNF. These findings suggest a role for TNF mediated destruction of Naegleria trophozoites by neutrophils in host defense, and that ingestion of host neutrophils by Naegleria trophozoites may represent a virulence factor. PMID- 2316794 TI - Systemic disease in Peromyscus leucopus associated with Borrelia burgdorferi infection. AB - Sixteen wild Peromyscus leucopus, trapped for the establishment of a breeding colony, developed signs of neurological damage (trembling, incoordination, circling, head tilt, and lameness of the rear legs) 2-47 days after capture in southern Wisconsin. Spirochetes were cultured from the brain of 5/11 mice, and Borrelia burgdorferi was cultured from 1 brain. A spirochete was isolated from the bladder of 1 mouse. The spirochete was identified by fluorescent antibody staining with the monoclonal antibody specific for B. burgdorferi, H5332. Serum antibodies to the spirochete were found in 14/15 mice. Negative results were obtained in all tests for viruses and bacteria, including Listeria (2/2), Mycoplasma (2/2), mouse hepatitis virus (10/10), Theilers's encephalomyelitis virus (GD VII) (8/8), REO 3 virus (2/2), and lymphocytic choriomeningitis virus (4/4). There was no bacterial growth from brains cultured on eosin methylene blue or blood agar (3/3). Histologic lesions included nonsuppurative cellular infiltrates in the brain, kidney, liver, and lung. Three outbred Swiss-Webster mice were inoculated orally with a suspension of the brain in BSKII medium, and 3 were inoculated with unpassed B. burgdorferi cultured from the brain of a P. leucopus with motor dysfunction. Five of the inoculated mice developed antibody titers of 1:128; one mouse was positive at 1:256. Motor signs of neurologic damage developed in 3/6 mice 2-24 weeks post-inoculation, and B. burgdorferi was detected in the brains of 2 mice by isolation and by fluorescent antibody. PMID- 2316795 TI - Pharmacokinetics of three commercial antivenoms in patients envenomed by the Malayan pit viper, Calloselasma rhodostoma, in Thailand. AB - The pharmacokinetics of 3 monospecific antivenoms were compared in patients envenomed by the Malayan pit viper, Calloselasma rhodostoma. There was a biphasic decline in serum concentrations following intravenous administration. The initial rapid decline was attributable to the formation of venom-antivenom complexes, as the fall in antivenom during this phase was positively correlated with the initial venom concentration (P = 0.045). The total apparent volume of distribution for each antivenom was 1.5-3 times larger than that of the central compartment, which suggests some tissue distribution in addition to complex formation. This was marked for antivenom from the Government Pharmaceutical Organization of Thailand which contained mostly F(ab)2 fragments. The terminal elimination half time was shorter for Twyford antivenom of caprine origin. Systemic clearance was lower for Thai Red Cross antivenom. In 8 of the 26 patients who experienced recurrence of non-clotting blood after initial response to antivenom, serial measurements of plasma venom and antivenom concentrations revealed that recurrence of venom antigenemia and non-clotting blood bore no direct relation to the elimination half-life of the antivenom used, but non clotting blood recurred when serum antivenom levels fell below 10-20% of the total given. There is no substitute for close monitoring of envenomed patients so that indications for further antivenom can be detected promptly. PMID- 2316796 TI - Lethal paralytic shellfish poisoning in Guatemala. AB - An outbreak of paralytic shellfish poisoning occurred in Champerico, on the Pacific coast of Guatemala, July-August 1987. Of 187 people affected with characteristic neurologic symptoms, 26 died. A case study implicated a species of clam, Amphichaena kindermani, harvested from local beaches as the vehicle of the neurotoxins (saxitoxins). Children less than 6 years old had a higher fatality rate (50%) than people greater than 18 years of age (7%). The minimum lethal dose for 1 child was estimated to have been 140 mouse units of toxin/kg body weight; thus children may be more sensitive to the saxitoxins than are adults. This is the first large outbreak of paralytic shellfish poisoning recognized in Guatemala. PMID- 2316797 TI - Proper timing of surgery for gallstone pancreatitis. PMID- 2316798 TI - Abdominal trauma and diagnostic peritoneal lavage revisited. PMID- 2316799 TI - Venous thromboembolism in patients with major trauma. AB - The risk of venous thromboembolism after trauma is thought to be high, but the specific risk factors and the incidence of venous thromboembolism in the trauma population are poorly defined. Between October 1, 1987, and March 1, 1988, 719 patients were evaluated; 542 had no risk factors and 177 had at least 1 risk factor. No venous thromboembolism occurred in any of the 542 patients without a risk factor, whereas 12 of 177 patients (7%) with at least 1 risk factor had a venous thromboembolism. Pneumatic compression hose was the most common form of prophylaxis used, but it could not be applied to 35% of limbs because of plaster immobilizers, external fixators, complex wounds, or traction. In the high-risk group, 25 patients (14%) received no prophylaxis because of a physical impediment to application of these hose and a contraindication to anticoagulation. Age greater than 45 years was the only risk factor predictive of venous thromboembolism by logistic regression analysis. Patients with more than one risk factor had a significantly higher incidence of venous thromboembolism than those with only one risk factor. We conclude that a selected subgroup of trauma patients appears to be at risk of venous thromboembolism and should receive prophylaxis. Approximately one in seven high-risk patients cannot receive anticoagulant or mechanical prophylaxis because of their injuries. PMID- 2316800 TI - Factors influencing postoperative urinary retention in patients undergoing surgery for benign anorectal disease. AB - One hundred eleven patients who had undergone surgery for benign anorectal disease under spinal anesthesia were studied retrospectively to determine the incidence of postoperative urinary retention requiring catheterization and to assess possible influences on that incidence. The age group and sex of the patients did not affect the rate of retention. However, the use of a long-acting anesthetic agent and the administration of at least 1,000 mL of intravenous fluid perioperatively each produced a significant increase in postoperative urinary retention. PMID- 2316801 TI - Emergency department deaths. AB - This study reviews 186 deaths resulting from trauma in a 2-year period in the Charity Hospital of Louisiana at New Orleans Accident Room in order to evaluate problems in prehospital and hospital resuscitative care. All subjects underwent autopsy, and only six were found to have injuries compatible with survival. Three of these were late arrivals (by transfer or self-imposed delay) and died of protracted hemorrhage. Only three deaths occurring in the Emergency Department itself were found to have been potentially preventable. The important factors in maximizing survival of trauma patients remain rapid transport; immediate, appropriate, rapid evaluation; and quick diagnosis, resuscitation, and definitive therapy. These require a well-trained emergency medical ambulance service delivering patients quickly to a hospital designed to handle trauma patients. One person, preferably a general surgeon with trauma experience, should supervise and monitor the patient continually until the resuscitation phase and all diagnostic tests are completed and definitive therapy is initiated. PMID- 2316802 TI - Operative cholangiography. AB - The value of operative cholangiography in the management of biliary tract disease has been questioned. To better define the role of cholangiography, we reviewed 579 consecutive cholecystectomies done by 1 group of surgeons in a small rural practice over 8 years. Cholangiography demonstrated unsuspected common bile duct disease in 5% of the procedures, while 12% of the patients were spared an unnecessary choledochotomy after a normal cholangiogram was obtained. There was no morbidity, mortality, or prolongation of the hospital stay attributed to the cholangiographic procedure. These findings bolster the argument for routine cholangiography as a safe, effective, and helpful screening examination for patients who are at risk for having common bile duct disease. PMID- 2316803 TI - Obstructed intestine as a reservoir for systemic infection. AB - Intestinal motility, absorption, and secretion are altered after intestinal obstruction, but at what point the normal bacterial barrier function of the viable gut fails after intestinal obstruction is unclear. Thus, we tested whether after simple intestinal obstruction bacteria would translocate across the viable intestinal wall to cause systemic infection. Within 6 hours of intestinal ligation 1 cm proximal or distal to the ileocecal valve, bacteria had translocated to the mesenteric lymph nodes, and by 24 hours after intestinal obstruction, bacteria had spread to the liver, spleen, and blood stream. Bacterial translocation rarely occurred in the animals undergoing laparotomy and sham intestinal ligation, indicating that bacterial translocation was not due to surgical stress. Based on the results of these studies, bacterial translocation induced by intestinal obstruction appears to be due to disruption of the ecology of the normal gut microflora, leading to intestinal overgrowth with certain enteric bacilli and mucosal damage. Although the exact mechanism(s) by which simple mechanical obstruction injures the intestine is not known, the fact that mucosal injury did not occur in germ-free mice suggests that bacteria may play a role in the pathogenesis of obstruction-induced intestinal injury. PMID- 2316804 TI - Thirty years' experience with biliary tract reconstruction by hepaticoenterostomy and transhepatic T tube. AB - This study shows long-term results of biliary tract reconstruction in cases of high stenosis of the hepatic duct. Hepaticoenterostomy was performed with transhepatic insertion of a T tube following an original technique. A portion of the horizontal limb of the T tube is placed in the left hepatic duct, the other portion in the duodenum or jejunum, and the vertical limb extends into the right hepatic duct and the right lobe of the liver and is brought out through the abdominal wall. This tube is irrigated daily and removed after 12 months in order to keep the stent in place for a sufficient duration to prevent stenosis. This technique was used in 45 patients who underwent operations from 1954 to 1984. There were 6 postoperative deaths. Of the 39 patients discharged from the hospital, 37 were followed up. Excellent results were obtained in 30 patients who remained asymptomatic after observation from 1 to 14 years. In three patients, results were good, but there were occasional episodes of fever that subsided with antibiotics; one of these patients was observed for 17 years. Results were poor in four patients who developed a recurrent stenosis; three of them underwent reoperations, with satisfactory results. Long-term observation has shown that the described surgical procedure is useful in cases of high stenosis of the hepatic duct, because a stent can be left in place for a year and usually will prevent stenosis at the biliary intestinal anastomosis. PMID- 2316805 TI - Treatment of enterocutaneous fistulas by high-pressure suction with a normal diet. AB - The treatment of enterocutaneous fistulas has dramatically changed in recent years with the advent of total parenteral nutrition, which continues to be the most utilized and efficient means of cure. However, the cost of the treatment and long-term hospitalization represent real problems. We were able to obtain clinical cure in some patients with an inexpensive and simple high-pressure suction method, so we examined an experimental model in an attempt to define the usefulness and feasibility of this technique. PMID- 2316806 TI - End-to-end anastomosis by enclosure between a prosthesis and a vessel with a significant difference in diameter. AB - A technique is described that allows an end-to-end anastomosis between a vascular prosthesis and a vessel that is much smaller in diameter. This procedure involves enclosing the prosthesis and the vessel while keeping the vascular axis straight without any kinking. In addition, this technique makes little demand on the extensibility of the natural tissue in order to adapt to the prosthesis, which is inextensible. PMID- 2316807 TI - Surgical implications of the posterior gastric artery. AB - The posterior gastric artery was identified during gastrectomy in 43 of 51 patients with distal gastric cancer. Two female patients had two posterior gastric arteries that originated separately from the splenic artery. Of these 45 arteries, 6 originated from the proximal third of the splenic artery, 35 from the mid third, and 4 from the distal third. These vessels coursed upward behind the posterior parietal peritoneum. The anterior and posterior walls of the remnant stomach were stained blue after injection of methylene blue solution into the splenic artery. The surgical importance of the posterior gastric artery is obvious because of its high frequency and deep origin and course. In addition, it is another source of blood supply to the stomach, and the lymphatics around this vessel form one of the primary routes draining the gastric fundus. PMID- 2316808 TI - Structured single-observer methods of evaluation for the assessment of ward performance on the surgical clerkship. AB - This study compares the traditional method (TM) of evaluating ward performance on the surgical clerkship with four structured, single-observer methods (SSOM) of evaluating the clinical skills demonstrated in patient workups, progress notes, physical examination, and technical performance. SSOM differed from TM in preciseness of evaluation criteria, training of evaluator, and amount of direct observation of clinical performance. SSOM appeared to be a more precise measurement instrument than TM and far more sensitive to the detection of clinical improvement. The study documents the significant contribution of a nurse educator to the evaluation process, as this contribution correlates well with TM yet provides a unique and independent perspective. Finally, SSOM of evaluation correlated significantly with oral examination and the National Board of Medical Examiners (NBME) test results. Addition of SSOM to TM is recommended for clerkship evaluation of ward performance. PMID- 2316810 TI - Righteousness in medicine. Who really wins? PMID- 2316809 TI - Syringosquamous metaplasia. A distinctive eruption in patients receiving chemotherapy. AB - Squamous metaplasia of the upper portion of the sweat ducts has been observed in four patients who received chemotherapy; two patients with acute myelogenous leukemia, one patient with testicular carcinoma, and one patient with anaplastic carcinoma of the lung. This change is different (but perhaps related) from what is described in neutrophilic eccrine hidradenitis in patients with acute myelogenous leukemia and other tumors after chemotherapy. Syringosquamous metaplasia may be confused with well differentiated squamous cell carcinoma histologically. PMID- 2316811 TI - Focal acantholytic dyskeratosis occurring in pityriasis rubra pilaris. PMID- 2316812 TI - Tubulin expression in melanocytic skin tumors. An immunohistochemical study. AB - The microtubulus system as a part of the cellular cytoskeleton contributes to cell movement. Microtubulus assembly and disassembly is considered to be essential for tumor invasion and serves as a target for tumor chemotherapy. Using immunohistochemical methods, we investigated the distribution of tubulin in normal skin and 34 melanocytic skin tumors. In normal skin, tubulin was strongly expressed in dermal nerves, melanocytes, fibroblasts within the papillary dermis and in myoepithelial cells. In melanocytic skin tumors, nevus cells and melanoma cells stained positive, particularly at the periphery of the lesions, where there were single cells and small nests. The main difference between benign and malignant melanocytic tumors was found in the stromal cells: In melanocytic nevi, the stromal fibroblasts were entirely tubulin negative; whereas, adjacent to the invasive edge in primary and metastatic malignant melanoma, the stroma fibroblasts were strongly positive. Our results show that tubulin is regularly expressed in melanocytic skin tumors and may serve as a prerequisite for cell movement. The pronounced expression of tubulin in fibroblasts surrounding malignant melanocytic skin lesions reflects a stromal alteration that might contribute to tumor invasion. PMID- 2316813 TI - An immunohistochemical study of dermatofibrosarcoma protuberans supports its fibroblastic character and contradicts neuroectodermal or histiocytic components. AB - Paraffin-embedded material from 26 cases of dermatofibrosarcoma protuberans (DFSP) was investigated by the peroxidase-antiperoxidase technique. Antibodies to S-100 protein, Leu-7 antigen, and neuron-specific enolase (neural markers); to lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin (histiocytic markers); and to cytokeratin, desmin, vimentin, and factor VIII were used. The tumor cells reacted only for vimentin. In addition, 12 cases showed positive reactions with histiocytic markers (1-3% of the cells; in two cases, up to 10%). These results support a fibroblastic and contradict a neural or histiocytic histogenesis of DFSP. PMID- 2316814 TI - Tufted folliculitis. A specific bacterial disease? AB - Residual groups of hair follicles and unusual "tufts" of multiple hairs emerging from single follicular openings have been described in scarring alopecia associated with staphylococcal infection. Various mechanisms have been proposed to explain these findings. Histological study of four cases suggests that retention of telogen hairs through several hair cycles may be responsible for this phenomenon. PMID- 2316815 TI - Quantification of histologic features of dysplastic nevi. AB - We quantified the histologic features of 100 consecutive dysplastic nevi. Although there is heterogeneity in the microscopic attributes of dysplastic nevi, certain features that are seen repeatedly should enable the histologic identification of these melanocytic neoplasms. These features include a central dermal nevocytic component with a peripheral extension of a junctional component, elongated epidermal rete ridges, bridging of nests of melanocytes at the dermo epidermal junction, nests of melanocytes at the sides of rete ridges as well as at their bases, and concentric eosinophilic fibrosis. Cytologic features of melanocytes were not as valuable as architectural features of individual nevi in classifying these lesions. We also provide an atlas of selected histologic features that depicts some aspects of this heterogeneity. PMID- 2316816 TI - Electron microscopy of the effects of dithranol on healthy and on psoriatic skin. AB - The fine structure of healthy and of psoriatic skin was studied after dithranol irritation. Following a minimum erythematogenic or a moderate-to-considerable irritant reaction of healthy skin with dithranol, all epidermal cell types were focally affected. The Langerhans' cells (LC) were most sensitive, reacting with strongly swollen mitochondria with broken cristae, and sometimes by forming branched and circular Birbeck granules. More often than is normal, the Birbeck granules showed continuity with the LC cytomembrane. Also, melanocytes were more sensitive than keratinocytes. Most of the more strongly affected keratinocytes became cytolytic with edemic cytoplasm, but scattered cells underwent dyskeratosis (apoptosis) resulting in colloid bodies in the upper dermis. High amounts of lipid droplets developed in the basal keratinocytes, LCs, melanocytes, and dermal cells. Lipid droplets also developed in the keratinocytes at the stratum granulosum/stratum corneum interface concomitantly with a decrease in keratohyalin. Ten days after challenge, keratohyalin granules were normal again, but otherwise many changes in epidermis persisted, with increased numbers of exocytic cells and LC-mononuclear cell contacts in the epidermis and immunocompetent cells crossing the dermal-epidermal junction. These findings indicate that an irritant reaction could predispose to sensitization via nonspecifically activated immunocompetent cells. A single half-hour contact treatment with dithranol caused negligible changes in the psoriatic skin, while 24 hours' occlusion caused moderate-to-massive changes in mitochondria of keratinocytes, resulting in giant perinuclear mitochondria with broken cristae. Dithranol affects all cell types in the skin and morphologically it cannot be concluded which effect is the important one in clearing the psoriatic lesions. PMID- 2316817 TI - Follicular lymphomatoid papulosis. AB - A case of follicular lymphomatoid papulosis was studied by light- and electron microscopic methods. The nature of atypical cells was analyzed with monoclonal antibodies. This case proved to be mainly a type B lymphomatoid papulosis with a predominance of T-helper markers in atypical lymphoid cells. All previously reported cases of this rare variant corresponded to type A lymphomatoid papulosis. Therefore we believe this to be the first case report of type B follicular lymphomatoid papulosis. PMID- 2316819 TI - Superficial mucoceles of the oral mucosa. AB - Superficial mucoceles are innocuous vesicular lesions that have been mistaken for mucous membrane pemphigoid. Clinically they are asymptomatic, small, clear, tense vesicles that have a predilection for the retromolar pad area, posterior buccal mucosa, and soft palate. Microscopically they are subepithelial extravasations of sialomucin that occur at the epithelial connective tissue interface. Minor salivary gland ducts are present in the immediate vicinity of the lesions and are a clue to the correct diagnosis. Demonstration of sialomucin is diagnostic. PMID- 2316818 TI - Giant cytoplasmic granules in Langerhans cells of Chediak-Higashi syndrome. AB - Giant membrane-bound cytoplasmic granules were found in the epidermal Langerhans cells of a patient with the Chediak-Higashi syndrome. These cells also contained normal-appearing Birbeck granules. The giant granules had a granular or sometimes globular internal structure; they are believed to derive from fusion of lysosomes or some portion of Birbeck granules. It is unclear whether this morphologic change in Langerhans cell interferes with their antigen-presenting function; it may be, in part, responsible for the frequent infections seen in patients with Chediak-Higashi syndrome that are otherwise more clearly related to the abnormalities in neutrophils and lymphocytes. The Langerhans cell is another cellular type in Chediak-Higashi syndrome in which giant cytoplasmic granules are found. PMID- 2316820 TI - Comparative evaluation between two immunoenzymatic techniques (FAST and Phadezym) and the Phadebas RAST in food allergy. AB - The diagnosis of food IgE-dependent hypersensitivity is based on the demonstration of specific IgE, completed by provocation tests. Two immunoenzymatic techniques, the Phadezym and the FAST, are compared with the Phadebas RAST, in 86 sera (23 controls, 28 from patients with a reported food allergy and 35 with a positive RAST to a food allergen). The within-run variation coefficient of class 0-2 sera was 9% for the Phadebas RAST, and higher than 20% for the Phadezym and the FAST. It was in order of 8.7%, 9.4% and of 17.6% respectively for Phadebas RAST, Phadezym and FAST when estimated with class 3-4 sera. The specificity was higher than 95% for the three techniques. The sensitivity was 75% for Phadebas and 43% for Phadezym and FAST. The FAST test is much less sensitive with allergens of vegetal origin than those of animal origin (P less than 0.01). This work indicates the high percentage of false negative results of immunoenzymatic techniques when food extracts are tested. This could be explained either by an enzyme-substrate reaction or by a non-specific inhibition of the enzyme linked to the anti-IgE IgG. PMID- 2316821 TI - Developmental change of chironomid allergen during metamorphosis. AB - The development of allergen during metamorphosis of chironomids, Chironomus yoshimatsui and Tokunagayusurika akamusi, was studied by means of ELISA inhibition with pooled serum containing high titer of specific IgE to each adult midge. Extracts of C. yoshimatsui larvae and pupae did not inhibit the specific IgE antibody to adult C. yoshimatsui. Mature adult C. yoshimatsui extract had about 10 times more inhibitory substance than the young adult. Hemoglobin, however, was degraded during the metamorphosis as measured by spectrophotometry and HPLC. The inhibitory substance against specific IgE antibody to adult T. akamusi was identified as highest in female body, less in egg, and even less in wing, leg and male body. The size of the substance in egg and female body was estimated at greater than 500 kD of molecular weight. PMID- 2316822 TI - Inhibition of histamine skin flare reaction following repeated topical applications of capsaicin. AB - The intention was to clarify, experimentally, some of the clinical properties of capsaicin. The modulation of histamine-induced immediate inflammatory responses following subsequent topical applications of capsaicin was studied. A gradual dose-dependent reduction of the acute inflammatory reaction was observed after daily epicutaneous application of 1% capsaicin for 6 days. The modulation suggests that the small nerve fibres responsible for the neurogenic spread of the flare gradually become less excitable. After termination of capsaicin applications the flare returned to its initial value after 9 days. The recovery phase was longer than the inhibition phase, probably due to slow repletion of neuropeptides in the cutaneous nerve endings. PMID- 2316823 TI - Stinging insect allergy: sensitization to vespids in Madrid and surroundings. Cross-reactivity study. AB - The study comprised 28 patients from the centre of Spain (Madrid and surroundings) who had suffered systemic reactions when stung by vespids. Specific IgE antibodies to Vespula spp. and Polistes spp. venoms were measured by RAST. All patients had positive RAST to Vespula venom and half of them also had positive RAST to Polistes venom. A patient can be sensitive to both venoms due to either a clinical sensitization to both venoms, or common antigenic determinants. To differentiate these states we used a RAST inhibition assay. We could inhibit Polistes RAST with either Polistes or Vespula venom to a similar degree. Inhibition of Vespula RAST was possible with Vespula venom, but only to a limited degree with Polistes venom. Direct RAST and RAST inhibition studies indicate that in our geographic region sensitization to Vespula venom is more common than to Polistes venom and Polistes might have cross-reactivity in our patients. PMID- 2316824 TI - Hyposensitization in asthmatics with mPEG-modified and unmodified house dust mite extract. IV. Occurrence and prediction of side effects. AB - A double-blind study on hyposensitization (HS) with two extracts prepared from the house dust mite Dermatophagoides pteronyssinus (Dp) was performed on a group of asthmatics with bronchial sensitivity to Dp. In 18 patients, aluminium hydroxide was added to the Dp-extract to give a depot effect (Dp-group). Nineteen patients were treated with a similar extract in which allergenicity had been reduced by coupling to monomethoxypolyethylene glycol (mPEG-Dp-group). This extract had previously been shown to have less effect on clinical symptoms and skin sensitivity compared to the Dp-extract. In the Dp- and mPEG-Dp-groups, 778 and 675 injections were administered. Fifteen and 12 patients in the Dp- and mPEG Dp-groups had systemic reactions (P greater than 0.05). The frequency of injections giving systemic reactions was reduced in the mPEG-Dp-group: 5.1% compared to 9.0% in the Dp-group (P less than 0.01). In the mPEG-Dp-group, reactions were mild to moderate, mainly late-occurring asthma and urticaria, whereas two episodes of anaphylaxis and four of severe asthma occurred in the Dp group. The reduction in side effects seems promising, but a further dose increase in the mPEG-Dp-group would be necessary to compare the side effects of doses with equal therapeutic effectiveness. High frequency of late local reactions made dose increase impossible with the present slightly modified extract. The systemic side effects occurred more frequently in patients highly skin test-sensitive to Dp prior to treatment. All patients skin test-positive to less than or equal to 100 BU had systemic reactions. Systemic side effects could not be predicted from the size of previous local reactions. PMID- 2316825 TI - Environmental factors in the first months of life and the possible relationship to later development of hypersensitivity. AB - The results of skin prick test (SPT) with common aeroallergens (in 870 severely asthmatic children, average age at testing 8.1 years) were analysed and compared with the results of a questionnaire about pets and smoking habits in the children's homes during the first 6 months of life. The study indicates a possible correlation between early massive exposure to certain allergens (cat, timothy) and later development of hypersensitivity. No conclusion can be drawn about a possible role of tobacco-smoking. PMID- 2316826 TI - Delayed-type hypersensitivity skin testing: variance among Trichophyton species extracts. PMID- 2316827 TI - Allergy to storage mites in asthmatic patients and its relation to damp housing conditions. AB - The relation between allergy to house dust mites and allergy to storage mites was studied in 326 patients with bronchial asthma. A positive RAST to house dust mites was found in 24.5% and to storage mites in 7.4%. There was a close association between a positive RAST to house dust mites and a positive RAST to storage mites, and 91.6% had a positive RAST to both. Only 0.9% with a negative RAST to house dust mites had a positive RAST to storage mites, whereas the frequency was 27.5% in those with a positive RAST to house dust mites. Present occupation with exposure to storage mites was found in 20.8% with a positive RAST to storage mites. A positive RAST to both house dust mites and storage mites was significantly associated with anamnestic indicators of damp housing conditions. The close association between allergy to house dust mites and allergy to storage mites in this study is probably caused by a common environmental factor, i.e. damp housing conditions. PMID- 2316828 TI - Evaluation of the Phadiatop test in an epidemiological study. AB - Sera from 204 adult patients with chronic airways obstruction were analysed with the Phadiatop, a new allergosorbent test with a paper disc containing the most relevant inhalant allergens, the PRIST for total IgE determinations, and a panel of seven RAST tests with the common inhalant allergens in The Netherlands as reference. The aim was to evaluate the Phadiatop as screening test in the in vitro diagnostic procedures in an epidemiological setting. The Phadiatop was classified positive or negative according to percentage binding, total IgE was considered elevated at values greater than 100 kU/l and the RAST panel positive when at least one RAST result was class greater than 1. The prevalence of inhalant atopy came to 27.9%. The predictive value of the Phadiatop for a positive RAST panel was 96.4%, and for a negative RAST panel 97.3%. For the PRIST these values were 51.9% and 87.2% respectively. The correlation between the log percentages binding of the Phadiatop and the RAST panel was 0.93. It is concluded that the Phadiatop is a valuable test for the screening of inhalant atopy, and as the percentage binding of the Phadiatop may reflect the degree of sensitization it could also be applied as a quantitative measure especially for epidemiological purposes. PMID- 2316829 TI - Metachromatic cells in nasal mucosa after allergen challenge. AB - Metachromatic cells in the nasal mucosa were studied in relation to symptoms in 16 schoolchildren and 11 adults with hay fever who were challenged with pollen outside the pollen season, using either a gentle scraping-cytocentrifugation method for collection of mucosal specimens or biopsies. There was a temporary redistribution of metachromatic cells towards the mucosal surface appearing 5-24 h after challenge, with a correlation between the quantity of metachromatic cells and symptom scores. Thus, a single exposure to high doses of allergen may contribute to priming in susceptible individuals. PMID- 2316830 TI - Change of clinical practice. PMID- 2316831 TI - Local anaesthesia for eye surgery. The peri-ocular technique. AB - A technique of peri-ocular infiltration of local anaesthetic for eye surgery is described. The ease of administration of this form of local blockade is highlighted and its low propensity for complication compared with retrobulbar blockade. The involvement of anaesthetists in the performance of local anaesthesia for ophthalmic surgery that utilises this technique is encouraged. PMID- 2316832 TI - Tussive effect of a fentanyl bolus administered through a central venous catheter. AB - One hundred and ten male patients scheduled for coronary artery bypass grafting were allocated randomly into one of three groups. Patients in group A received fentanyl 7 micrograms/kg via a central venous catheter, those in group B were given fentanyl 7 micrograms/kg through a peripheral venous cannula, and patients in group C received sterile water via a central venous catheter. In group A, 45.9% of patients coughed after injection of fentanyl; the mean onset time from the end of fentanyl administration to the beginning of coughing was 10.6 seconds. Only one patient in group B and no patient in the control group exhibited a cough response (p less than 0.0001). We hypothesise that fentanyl can evoke the pulmonary chemoreflex. PMID- 2316833 TI - Cardiac arrest after isoflurane anaesthesia in a patient with Duchenne's muscular dystrophy. AB - An 8-year-old boy known to have Duchenne's muscular dystrophy suffered a cardiac arrest 10 minutes after he regained consciousness after isoflurane anaesthesia for an orchidopexy procedure. Resuscitation was successful 2 hours after the start of external cardiac compression and after correction of hyperkalaemia and the administration of dantrolene. He later developed myoglobinuria elevated creatine kinase and a metabolic and respiratory acidosis. He demonstrated a delayed increase in rectal temperature. PMID- 2316834 TI - Accidents, near accidents and complications during anaesthesia. A retrospective analysis of a 10-year period in a teaching hospital. AB - A retrospective analysis is presented of all reports of faults, accidents, near accidents and complications associated with anaesthesia in one hospital from 1978 to 1987. 113,074 anaesthetics were administered in that period, of which 97,496 were for noncardiac procedures. There were 148 reports; 39 were of dental damage. Peri-operative cardiac arrests during noncardiac surgery were reported 29 times. Sixteen of these were fatal. Anaesthesia was thought to have played an important role in 13 cardiac arrests (1 per 7500 anaesthetics) and six were not successfully resuscitated (1 per 16,250 anaesthetics). There were 12 reports of postoperative peripheral neuropathies (1 per 9422 anaesthetics). Failure to check, lack of vigilance and inattention or carelessness were the most frequently associated factors with the rest of the reports. PMID- 2316835 TI - 'Leopard' syndrome. AB - 'Leopard' syndrome is a rare inherited disorder associated with a high prevalence of cardiac abnormalities. General anaesthesia for dental treatment in a patient who had cardiomyopathy and bizarre electrocardiographic abnormalities associated with this syndrome is described. A thorough cardiac assessment is advised in a patient with multiple lentigines, although no clinical symptoms or signs may be found. Even if no cardiac abnormality is found before it is better to re-assess the patient, since abnormalities may develop later. The assessment should be repeated if any abnormality was detected before but without clinical significance, since the disease is progressive and may progress more rapidly in some patients than in others. PMID- 2316836 TI - Acute infective airway obstruction associated with subglottic stenosis. AB - Pre-existing subglottic stenosis in a 22-month-old child with laryngotracheobronchitis resulted in failure to intubate the trachea on the intensive therapy unit. Tracheostomy was necessary in the operating theatre to secure the airway. The implications for safe management are discussed. PMID- 2316837 TI - The Keeler Pulsair air impulse tonometer. Comparison with the Perkins hand-held applanation tonometer for peri-operative measurement of intra-ocular pressure. AB - The Keeler Pulsair is a noncontact tonometer which can be used by those without specialist ophthalmic training. The instrument was compared, in a series of 30 patients in whom a total of 150 readings were taken, in respect of accuracy, ease and speed of use, and acceptability to patients, with the Perkins hand-held applanation tonometer. There was good correlation between measurements obtained with the two instruments: r = 0.92, (p less than 0.001); the Pulsair was described as easy to use in 87% of subjects, and no patient found the procedure unpleasant. The median times taken for Pulsair measurements were 7 (range 4-14) seconds for a single reading in conscious patients, and 11 (range 4-29) seconds for four readings in anaesthetised patients. These times were significantly quicker than those recorded with the Perkins tonometer which were 83 (range 66 138) seconds and 20 (range 8-45) seconds respectively (p less than 0.001). We conclude that the Pulsair is suitable for use by those who are not ophthalmologists for the rapid measurement of intra-ocular pressure changes during anaesthesia. PMID- 2316838 TI - Effect of metoprolol and diazepam on pre-operative anxiety. AB - A double-blind study of 98 patients who underwent elective hysterectomy or orthopaedic surgery was conducted to evaluate the effect of metoprolol or placebo combined with diazepam given 1-3 hours before surgery. Evaluation was by anaesthetists and by visual analogue scoring by the patients. The anaesthetists found that patients who received metoprolol were significantly less anxious (p less than 0.005) and better sedated (p less than 0.001) before induction of anaesthesia. The patients who received metoprolol found themselves more calm compared with placebo patients. Arterial blood pressure and heart rate were reduced by metoprolol compared to placebo. Metoprolol may be a valuable drug for premedication. PMID- 2316839 TI - Comparison of conventional and rapid inhalational induction of anaesthesia with enflurane. AB - Inhalational induction of anaesthesia using either a conventional method or a vital capacity breath of 4% enflurane in 67% nitrous oxide was compared in 30 adult surgical patients. Induction time was significantly faster in patients who took a vital capacity breath (71, SD 22 versus 132, SD 18 seconds, p less than 0.01). There were no significant differences between groups in respect of systolic blood pressure, heart rate, arterial oxygen saturation or incidences of excitement or coughing. The vital capacity breath method was acceptable to 87% of patients. PMID- 2316840 TI - A jet nebuliser for delivery of topical anesthesia to the respiratory tract. A comparison with cricothyroid puncture and direct spraying for fibreoptic bronchoscopy. AB - Topical anesthesia of the respiratory tract for fibreoptic bronchoscopy was compared, in a single-blind study, inhaled from a simple and inexpensive jet nebuliser, administered by cricothyroid injection or by a 'spray-as-you-go technique'. Each technique was supplemented by spraying lignocaine through the fibrescope and intravenous fentanyl-droperidol sedation. Inhaled nebulisation was successfully used for 96% (46 of 48) of patients, was safe, effective and acceptable to the patient and bronchoscopist. The cricothyroid injection method produced better conditions than nebulisation in patients who had diagnostic bronchoscopy. The nebuliser technique is as satisfactory as the spraying technique in patients for diagnostic bronchial lavage in whom bleeding from a cricothyroid puncture is unacceptable. Patients who used the nebuliser were more satisfied. This technique may also be a useful method for 'awake' intubation. PMID- 2316841 TI - Goldenhar's syndrome: an analysis of anaesthetic management. A retrospective study of seventeen cases. AB - Seventeen patients with Goldenhar's syndrome who had surgery 28 times are presented. Various authors have reported problems in the anaesthetic management of these patients, but we encountered significant difficulties in only one. Three anaesthetic techniques were used. A thorough pre-operative assessment with back up facilities for difficult intubation are important. Additional cardiorespiratory and craniovertebral anomalies may necessitate modifications in the basic techniques. PMID- 2316842 TI - Pulse oximetry in methaemoglobinaemia. PMID- 2316843 TI - Carboxyhaemoglobin. PMID- 2316844 TI - 'Intra-operative hearing' under general anaesthesia. PMID- 2316845 TI - Fear and anaesthesia. PMID- 2316846 TI - Possible malignant hyperpyrexia. PMID- 2316847 TI - Collapse of lung during hemithyroidectomy. PMID- 2316848 TI - Recurrent anaphylactoid reaction during caesarean section. PMID- 2316849 TI - The Graseby adult apnoea alarm. PMID- 2316850 TI - Respiratory arrest after caudal bupivacaine. PMID- 2316851 TI - Doxapram for respiratory depression after epidural morphine. PMID- 2316852 TI - The requirement for intensive care support for the pregnant population. PMID- 2316853 TI - Muscle spasticity. PMID- 2316854 TI - An unusual complication of varicose vein surgery. PMID- 2316855 TI - Hypotension and epidural for caesarean section. PMID- 2316856 TI - Recovery from two different intravenous induction techniques in identical twins. PMID- 2316858 TI - Abolition of injection pain due to propofol in children. PMID- 2316857 TI - Changes in haemodynamics and plasma catecholamine concentrations after field block for inguinal herniorrhaphy using lignocaine with adrenaline. AB - Haemodynamic changes and plasma catecholamine concentrations were measured in 12 patients aged 24 to 87 years after performance of a field block for elective repair of inguinal or femoral hernia. The local anaesthetic used comprised a mixture of lignocaine 0.5% with adrenaline 1:200,000; the dose of lignocaine administered varied from 3.8 mg/kg to 4.9 mg/kg. Plasma adrenaline increased by 326% and plasma noradrenaline by 75% at 10 minutes after completion of the block. Mean heart rate increased from 75 to 94 beats/minute after 20 minutes, whilst there were no obvious changes in systolic and diastolic arterial pressures. Potentially serious arrhythmias developed in two patients, thought to be related to the peak plasma concentrations of adrenaline produced. It is recommended that the dose of adrenaline used as described for this block should be reduced. PMID- 2316859 TI - Misassembly of Laerdal masks. PMID- 2316860 TI - Perforation of oesophagus by tracheal tube during resuscitation. PMID- 2316861 TI - Awake blind nasal intubation: use of a simple whistle. PMID- 2316862 TI - A self-retaining nasopharyngeal airway. PMID- 2316863 TI - Bain system for use with the circle absorption system. PMID- 2316864 TI - Damage to Manley ventilators. PMID- 2316866 TI - Damage to multidose vials. PMID- 2316865 TI - Burns from iodine. PMID- 2316867 TI - Failed cuff deflation. PMID- 2316868 TI - DNA sequencing, automation, and the human genome. AB - DNA sequencing is one of the key analytical operations of modern molecular biology and a crucial element of biotechnology. The principles of DNA sequencing and details of the technologies of both manual, radioisotope-based and automated, fluorescence-based approaches are described. The goals and rationale of the Human Genome Initiative are discussed along with implications for future sequencing technologies. Finally, a glimpse of emerging DNA sequencing technologies is offered. PMID- 2316869 TI - Mediated, anaerobic voltammetry of sulfite oxidase. AB - The anaerobic voltammetry of the Mo/Fe enzyme, sulfite oxidase (SO), is described for the mediators cytochrome c, [Ru(NH3)6]3+/2+, TMPD+/0, and [Co(bpy)3]3+/2+. Theory derived for steady-state voltammetric catalysis correctly predicts the observed concentration and scan-rate dependencies of the catalytic waves. The instances for which existing ECcat theories may be applied to two catalytic reactions coupled to an interfacial charge transfer are considered. The biomolecular rate constant for the reaction of [Co(bpy)3]3+ with reduced SO is calculated and determined to be approximately 5 X 10(4) L.mol-1.s-1. The appearance of catalytic prepeaks at low sulfite concentrations is noted and the shape of corresponding i/t curves from chronoamperometry is examined. The analytical implications of the novel time dependence of the catalytic current under these conditions are discussed. PMID- 2316870 TI - Effects of inaccurate reference lifetimes on interpreting frequency-domain fluorescence data. AB - The effects of assigning inaccurate reference lifetimes in lifetime determinations are predicted theoretically by using standard equations. This theory leads to a method to remove reference error effects using common least squares software. This method cannot, however, be used to deconvolute data collected with isochronal references. Uncorrected data can always be exactly solved with models containing one more degree of freedom than the true model. Monoexponential decays are fit by double-exponential decays or excited-state processes. Unimodal distributed decays often appear as discrete, double exponential decays. PMID- 2316871 TI - Elimination of z-ejection in Fourier transform ion cyclotron resonance mass spectrometry by radio frequency electric field shimming. AB - In Fourier transform ion cyclotron resonance (FT/ICR) mass spectrometry, coherent ion cyclotron orbital motion is produced by resonant radio frequency (rf) electric field excitation. However, because the excitation electrodes are of finite dimensions, the desired transverse (to the applied magnetic field) rf electric field is accompanied by an rf electric field component along the z- (magnetic field) direction, resulting in mass-dependent z-ejection and mass dependent FT/ICR mass spectral peak relative magnitudes. Addition of several "guard wires" of voltage-divided rf amplitude allows the rf electric field to be "shimmed" to near-perfect uniformity. In this paper (see also the accompanying paper by Russell et al.), we introduce two types of rf-shimmed ion traps. In the first type, guard wires are placed only in front of the trapping electrodes. In the second type, guard wire rings are placed inside the detector and trapping electrodes. For either arrangement, simion simulations were used to adjust the rf voltages applied (by use of voltage dividers) to the guard wires or rings so as to produce an optimally uniform rf field within the trap. The virtual elimination of z-excitation is confirmed by plots of magnitude-mode relative peak height vs ICR orbital radius. Because the guard wires (or rings) tend to shield the ions from the trapping electrode potential, the shift in ICR frequency with trapping voltage is also reduced, but not as well as by a screened trap.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316872 TI - Long path atomic/ionic absorption spectrometry in an inductively coupled plasma. AB - A novel approach was taken to increase the atomic/ionic absorption path length in an inductively coupled plasma (ICP) by using a water-cooled quartz "T-shaped" bonnet. Atomic and ionic absorption spectrometry was performed utilizing a continuum source and line sources. Absorption spectra of synthetic multielement solutions were collected with a photodiode array. Sample introduction into the ICP was accomplished with an ultrasonic nebulizer. To prevent the bonnet from cracking, low radio frequency powers were utilized (i.e., 400-600 W). Plasma diagnostics were performed to study the plasma temperature and electron number density within the "T-shaped" bonnet. Analytical figures of merit were found to be better than those obtained from previous work attempted with inductively coupled plasma atomic absorption spectroscopy and approaching that of flame atomic absorption spectroscopy. PMID- 2316873 TI - In vivo microdialysis and thermospray tandem mass spectrometry of the dopamine uptake blocker 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)-piper azine (GBR-12909). AB - Microdialysis in conjunction with thermospray tandem mass spectrometry was employed in following the time course of the experimental drug GBR-12909 in vivo. GBR-12909 is 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-3(phenylpropyl) piperazine. An important feature of microdialysis exploited in the method is the elimination of sample cleanup procedures. The detection limit was determined to be 100 pg and the relative standard deviation of estimates for standard solution in the range of 50 nmol/L to 1 mumol/L concentrations was found to be 17%. Important factors in obtaining high sensitivity and reproducibility were carrier phase composition and operation in the flow injection mode. The maximum concentration of GBR-12909 in the brain for a dose of 100 mg/kg i.p. was determined to be 250 nmol/L with the maximal concentration occurring approximately 2 h postinjection. This represents a 40-fold lower concentration of GBR-12909 in the brain as compared to cocaine concentration obtained at a dose of 30 mg/kg, which was estimated earlier under similar experimental conditions. This observation could explain the discrepancy between relative in vivo and in vitro potencies of the two drugs. PMID- 2316874 TI - Microchannel plate for surface-induced dissociation in mass spectrometry. AB - A new method for surface-induced dissociation of molecular ions, applied to tandem mass spectrometry, is achieved by collisions at a grazing angle on the inside channel surfaces of a microchannel plate. This technique, termed microchannel SID, is demonstrated by using both positive and negative parent ions in the energy range of 500-2000 eV. Fragmentation spectra of the pentapeptide leucine-enkephalin (555 daltons) at 500 eV show good sequence information with a net fragmentation efficiency of 14%. High mass fragmentation is demonstrated on (CsI)23Cs+ (6113 daltons), with the resultant spectrum showing all cluster fragments from n = 0 to 23. PMID- 2316875 TI - Bicontinuous microemulsions as media for electrochemical studies. AB - Biocontinuous microemulsions of didodecyldimethylammonium bromide (DDAB)/dodecane/water were explored as media for voltammetric reductions and oxidations of ruthenium(III) hexaammine, ferrocyanide, ferrocene, cob(II)alamin, and several polycyclic aromatic hydrocarbons (PAHs). These clear microemulsions are conductive and are believed to contain a dynamic extended network of interconnected water tubules. Agreement of simulated and experimental voltammetric data shows that electrochemical theory for homogeneous media is followed to a good approximation in DDAB microemulsions. Diffusion of electroactive solutes did not reflect the high bulk viscosities of the microemulsions. Non-polar molecules and ions diffuse as if they were in neat oil or aqueous media, respectively, and voltammograms with good signal to noise ratio are obtained. Reductions of PAHs in the microemulsions occurred by an ECE-type pathway, with nearly reversible one-electron reductions achieved at high scan rates. PMID- 2316876 TI - Continuous intercostal blockade with lidocaine after thoracic surgery. Clinical and pharmacokinetic study. AB - The efficacy and the side effects of a continuous infusion of lidocaine in the fifth intercostal space for the management of postoperative pain after lateral thoracotomy were evaluated in 20 adults. An indwelling catheter was inserted in the appropriate intercostal space before thoracotomy closure. After recovery from general anesthesia, a loading dose of 3 mg/kg of 1.5% lidocaine with epinephrine 1:160,000 was injected through the catheter, followed by a continuous infusion of 1% lidocaine without epinephrine at a rate of 1 mg.kg-1.h-1 for 54 h. In seven patients pharmacokinetic data were obtained. Pain, assessed by visual continuous analog scale, decreased from a median score of 8 (range, 7-10) to a score of 5 (range, 2-7) 20 min after the loading dose of lidocaine and continued to decrease until the end of the study (P = 0.0001). Complete cutaneous analgesia, assessed by pinprick test, was seen in a median of three thoracic spinal segments (range, 0-6) with partial cutaneous analgesia in seven segments (range, 6-9) 40 min after the loading dose, and levels that remained unchanged for 54 h (P = 0.0001). Peak lidocaine serum concentrations, 1.9 +/- 0.7 micrograms/mL, were present 9 +/- 3 min after injection of the loading dose. Serum concentrations of lidocaine under steady state conditions averaged 4.8 +/- 0.9 micrograms/mL (range, 3.5-5.8 micrograms/mL). This level under steady state conditions, though below the toxic level, suggests that additional bolus injection of lidocaine during the course of infusion might result in potentially toxic serum levels of lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316877 TI - Echocardiographic assessment of mitral valve function during mechanical cardiopulmonary resuscitation in pigs. AB - Using two-dimensional and M-mode echocardiography, mitral valve function was assessed during mechanical cardiopulmonary resuscitation (CPR). In 10 anesthetized pigs CPR began 1 min after induction of ventricular fibrillation; in all pigs three different compressive forces (200, 350, and 500 Newton [N]) were applied in randomized sequence for 3 min each, thus resulting in a reduction of anterior-posterior chest diameter by 15%, 20%, and 25%, respectively. Echocardiographic recordings of adequate technical quality were obtained from seven animals. During ventricular fibrillation, mitral valve leaflets showed fibrillatory movements without closure. During CPR systole with a compressive force of 200 N, the mitral valve closed in 114 of 700 CPR cycles (16%). This rate increased significantly (P less than 0.001) to 399 of 584 cycles (68%) with 350 N, and further to 470 of 494 cycles (95%) with 500 N. The higher mitral valve closure incidence was linked to statistically significant increases in systolic cerebral (+125%) and diastolic myocardial perfusion pressures (+136%) and cardiac output. We thus conclude that with low compressive force blood flow during mechanical CPR is due mainly to the chest pump mechanism, whereas the cardiac pump mechanism is effective with high compressive forces. PMID- 2316878 TI - Different effects of halothane and enflurane on diaphragmatic contractility in vivo. AB - We examined the effects of halothane and enflurane on diaphragmatic contractility in 12 anesthetized, mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Animals were randomly assigned to two groups, a halothane group (n = 6) and an enflurane group (n = 6). The Pdi stimulus-frequency relationship was compared at anesthetic levels of 1, 1.5, and 2 MAC (minimum alveolar concentration) in each group. The sequence of changing anesthetic concentration was randomized. In addition, the Pdi-frequency relationship was also compared between 1 MAC of halothane and enflurane in 8 of 12 dogs. In animals anesthetized with enflurane, Pdi significantly decreased with 50- and 100-Hz stimulation in the presence of increasing MAC values, whereas Pdi at 10-Hz stimulation was not affected by the depth of anesthesia. Pdi with 20-Hz stimulation during 2 MAC enflurane also decreased significantly below Pdi levels seen at 1 and 1.5 MAC. By contrast, with halothane there was no difference in Pdi at any of the stimulation frequencies during any of the three levels of anesthesia. There was no statistical difference, however, between Pdi-frequency relationships during 1 MAC of halothane and enflurane in eight animals. From these results, we conclude that halothane does not impair diaphragmatic contractility any more than enflurane does, but enflurane decreases force generation of the diaphragm at high stimulation frequencies in a dose-related fashion. This depressant effect of enflurane occurs mainly through the impairment of neuromuscular transmission and/or membrane excitability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316879 TI - Progressive changes in electroencephalographic responses to nitrous oxide in humans: a possible acute drug tolerance. AB - The possibility of acute tolerance to nitrous oxide was examined during halothane anesthesia in humans. Nitrous oxide was added to the inspired gas twice. The first admixture induced three successive stages of electroencephalogram (EEG): delta-waves lasting for 13 +/- 12 min, theta-waves lasting for 41 +/- 21 min, and, finally, spindle-type waves. The spindle-type EEG was similar to that of halothane anesthesia in configuration, but smaller in amplitude and faster in frequency than that seen during halothane anesthesia. The second admixture, given after a 20-30-min interval, induced a continuous delta-wave EEG in one patient, theta-waves followed by spindle EEG in eight patients, and spindle-type EEG in four patients. The successive changes of electroencephalographic response during the first admixture indicate that an alteration of central nervous system function occurred. The altered state was maintained in the absence of nitrous oxide: responses to a second admixture were characteristic of the later, altered, stages of responses seen after the first admixture. These findings support the view of acute tolerance to nitrous oxide. PMID- 2316880 TI - Efficacy of high-frequency jet ventilation in cardiac tamponade. AB - To evaluate the effects of high-frequency jet ventilation (HFJV) (f = 60, 120 breaths/min) and conventional mechanical ventilation (CMV) (f = 10, 20) during equivalent conditions of cardiac tamponade, stroke index (SI), intrapericardial pressure (IPP), airway pressure (P(aw)), and cardiac pressures were measured in anesthetized, paralyzed, chest-closed dogs with the same levels of PaCO2. Cardiac tamponade was produced by infusing normal saline into the intrapericardial space to increase IPP to either 8 mm Hg (group 1, n = 8) or 12 mm Hg (group 2, n = 8). Stroke index in group 1 was 7.3 +/- 0.8 during CMV (f = 10), 8.1 +/- 0.7 during CMV (f = 20), 10.9 +/- 1.4 during HFJV (f = 60), and 10.7 +/- 1.2 (mL.beat-1.m-2) during HFJV (f = 120). Stroke index in group 2 was 4.1 +/- 0.7, 5.1 +/- 0.5, 7.2 +/- 0.5, and 6.7 +/- 0.5 (mL.beat-1.m-2), respectively. In both IPP groups, stroke index values during HFJV were significantly higher than during CMV; however, there were no significant differences in mean left and right atrial transmural pressures between HFJV and CMV. Peak IPP, mean P(aw), and peak P(aw) during HFJV were significantly lower than those during CMV. The results indicate that HFJV with lower mean and peak Paw, and with lower mean and peak IPP, can result in higher cardiac output than CMV in cardiac tamponade. Thus, HFJV may be superior to CMV in the clinical management of cardiac tamponade. PMID- 2316881 TI - Incidence and prediction of postdural puncture headache. A prospective study of 1021 spinal anesthesias. AB - The incidence of postdural puncture headache (PDPH) was investigated prospectively in 873 consecutive patients undergoing a total of 1021 spinal anesthesias, and its association to age, sex, needle size, number of attempted dural punctures, needle bevel direction, duration of postoperative recumbency, and previous PDPH was analyzed. Multivariate analysis showed that age (P less than 0.0001), direction of the bevel of the needle when puncturing the dura mater (P = 0.022), and a history of previous PDPH (P = 0.018) were significant predictors of PDPH. The estimated relation between PDPH, on the one hand, and age and orientation of the bevel, on the other, enables the anesthetist to predict the risk of PDPH and thereby to choose an acceptable age limit for spinal anesthesia. PMID- 2316882 TI - Effects of epinephrine and ritodrine in dogs with acute hyperkalemia. AB - As plasma potassium concentrations, whether normal or elevated, can be reduced by intravenous administration of either epinephrine or ritodrine, the effects of these drugs were examined during acute hyperkalemia. Six anesthetized dogs were studied every 2 wk, on 18 separate occasions. Hyperkalemia was induced by intravenous infusion of potassium chloride, resulting in plasma potassium concentrations of 9.6 +/- 0.3 mEq/L (mean +/- SEM), bradycardia, and idioventricular rhythm. Dogs were then given slow intravenous injections every 30 min of either saline (controls), epinephrine, or ritodrine. Epinephrine doses were 0.01, 0.1, 1.0, 10, or 100 micrograms/kg; ritodrine doses were 0.1, 1.0, 10, 100, or 1000 micrograms/kg. At the highest does, both epinephrine and ritodrine caused clinically important decreases in plasma potassium, reducing concentrations to below 7.0 mEq/L. Ritodrine had a significantly greater effect than epinephrine. Side effects included hypertension and dysrhythmias with epinephrine, serious hypotension with ritodrine, and tachycardia with both drugs. For both drugs, the doses that caused a decrease in plasma potassium also caused an increase in heart rate and there was a correlation between plasma potassium levels and heart rate. Epinephrine and ritodrine may be useful in treating acute hyperkalemia, but cardiovascular side effects may occur. Increased heart rate could be used as an indicator of therapeutic effect and the magnitude of the increase in heart rate may be helpful in predicting the level of response. PMID- 2316884 TI - Lower esophageal sphincter integrity is maintained during succinylcholine-induced fasciculations in dogs with "full" stomachs. AB - During succinylcholine-induced muscle fasciculations, gastroesophageal barrier pressure in fasted adult dogs (n = 10) was compared by esophageal manometry with that in the same dogs with full stomachs. After fasting, fasciculations did not increase significantly either mean intragastric pressure (4.7 +/- 1.3 mm Hg before; 5.2 +/- 1.7 mm Hg during) or lower esophageal sphincter pressure (35.4 +/ 21.4 mm Hg before; 40.6 +/- 17.5 mm Hg during). Filling the dogs' stomachs with 300 mL of saline significantly increased both mean intragastric pressure (from 3.8 +/- 2.2 to 7.4 +/- 1.4 mm Hg) and mean lower esophageal sphincter pressure (from 20.2 +/- 6.8 to 28.6 +/- 14.8 mm Hg). Fasciculations did not produce a further increase in either mean intragastric or mean lower esophageal sphincter pressure. Most importantly, in all animals, under all conditions, gastroesophageal barrier pressure remained positive (range, 6.0-65.5 mm Hg) and therefore served as a barrier to passive regurgitation. PMID- 2316883 TI - Treatment of postoperative paralytic ileus by intravenous lidocaine infusion. AB - The effects of continuous intravenous infusion of lidocaine on postoperative paralytic ileus in cholecystectomized patients was investigated in this double blind study. An infusion of lidocaine (3 mg/min, n = 15) or an infusion of an equal volume of saline (n = 15) was started 30 min before induction of anesthesia and continued for 24 h after surgery. Postoperative colonic motility was evaluated by radiopaque markers and serial abdominal radiographs. A record was kept of the first passage of gas and feces. Results showed significantly earlier return of propulsive motility in the colon of lidocaine-treated patients. Radiopaque markers in the lidocaine group were propelled significantly earlier from the cecum/ascending colon to the transverse colon (P less than 0.05) and appeared significantly earlier in the descending colon (P less than 0.05) and the rectosigmoid colon (P less than 0.05) than in saline-treated patients. Despite the fact that the mean time for postoperative defecation occurred 17 h earlier in lidocaine-treated patients, differences between the groups were not statistically significant--a fact due, perhaps, to great individual variations in defecation habits. The time to first passage of gas, a variable representative of changes in anorectal or colonic tone rather than propagative motility, also did not differ significantly between the groups. No adverse reactions to lidocaine were reported. The results suggest that continuous intravenous infusion of lidocaine during the first postoperative day shortens the duration of paralytic ileus in the colon after abdominal surgery. Suppression of inhibitory gastrointestinal reflexes by reduction of postoperative peritoneal irritation is suggested as the mechanism of action. PMID- 2316885 TI - Evaluation of a forced-air system for warming hypothermic postoperative patients. AB - Thirty adult surgical patients admitted to the recovery room with an oral temperature less than or equal to 35.0 degrees C were randomized into two groups. Group 1 patients were covered with cotton blankets warmed to 37.0 degrees C, and group 2 patients were treated with a forced-air warming system. Mean oral temperature on admission to the recovery room was the same in both groups (34.3 degrees C). Oral temperature and the presence or absence of shivering were recorded at 15-min intervals. After application of the selected warming method, patients in group 2 were warmer at all time intervals. Mean temperatures in the forced-air heating group and in group 1 were, respectively, 34.8 degrees C and 34.3 degrees C (P less than 0.05) at 15 min; 35.0 degrees C and 34.2 degrees C (P less than 0.01) at 30 min; 35.2 degrees C and 34.5 degrees C (P less than 0.05) at 45 min; 35.8 degrees C and 34.7 degrees C (P less than 0.001) at 60 min; 36.0 degrees C and 35.0 degrees C (P less than 0.01) at 75 min; and 36.0 degrees C and 35.0 degrees C (P less than 0.01) at 90 min. The incidence of shivering was significantly greater in group 1 at 15 and 45 min. In addition, time spent in the recovery room was significantly greater in group 1 than in group 2, 156.0 min versus 99.7 min (P less than 0.003). PMID- 2316886 TI - Continuous spinal anesthesia with combined hyperbaric and isobaric bupivacaine in a patient with scoliosis. PMID- 2316887 TI - Pharmacokinetics of interpleural lidocaine administration in trauma patients. PMID- 2316888 TI - Anesthetic management of a pregnant patient with the hyperimmunoglobulin E (Job's) syndrome. PMID- 2316889 TI - Another complication of tracheal intubation. PMID- 2316890 TI - Vanishing calibration marks on a spinal catheter. PMID- 2316891 TI - Bupivacaine-induced cardiac arrest. PMID- 2316893 TI - Catecholamine release during isoflurane-induced hypotension. PMID- 2316892 TI - Iatrogenic pharyngeal pouch mimicking esophageal atresia: a diagnostic challenge to the anesthesiologist. PMID- 2316894 TI - Conical needles and transdural fluid leak. PMID- 2316895 TI - Decreased oxygen consumption during anesthesia and surgery: decreased metabolism or oxygen deficit? PMID- 2316896 TI - The infection control practitioner: an action plan for the 1990s. AB - Some articles have suggested that to survive in the 1990s an infection control practitioner (ICP) will have to be "smarter, brighter, or gone"--they assume that new initiatives for hospital peer review (utilization review, risk management, antibiotic use review, and quality assurance) soon will swallow up the ICP and the infection control program. This article questions that assumption. It reviews data supporting the continuing need for hospital infection control programs and presents information suggesting that the need for the ICP will increase rather than decline during the 1990s. Four essential characteristics for infection control programs are listed, and skills that make the ICP a valuable resource for other peer review programs are described. Several ways that the ICP can (and must) bring this information to the attention of other hospital personnel are suggested. Such actions help assure recognition of the continuing important role of the ICP and the hospital infection control program in each U.S. hospital and long-term care institution. PMID- 2316897 TI - Methodology to evaluate a computer-based system for surveillance of hospital acquired infections. PMID- 2316898 TI - Infection control in public health: a new perspective. AB - As public health continues to meet the challenges of old and new health risks, the practice of infection control will be an integral part of its services. The public health infection control program should include effective policies and procedures, in-service programs and implementation, and systems of surveillance specific to each department. Public health personnel must place emphasis on the practice of infection control in the community setting. The ICP who accepts this challenge will be in the forefront of infection control in public health. Infection control is a respected part of the hospital setting and now is the time for the ICP to tailor this program to the public health delivery system. PMID- 2316899 TI - Stability of anterior openbite treated with crib therapy. AB - The records of 33 openbite patients treated with cribs were collected. The sample was divided into two groups with group one comprised of 26 growing patients and group two comprised of seven nongrowing patients. There was a significant increase in overbite for both groups during treatment. The nongrowing group also showed a significant increase in overbite during the posttreatment period. During the posttreatment time interval 17.4 percent of the growing sample and zero percent of the nongrowing sample exhibited relapse. However, all patients who achieved a positive overbite during treatment maintained a positive overbite posttreatment. These findings suggest that patients who achieve a positive overbite with crib therapy have a good chance of maintaining this correction after orthodontic treatment is completed. This statement appears to be true for both growing and nongrowing patients. The reason for this increased stability may be due to a modification of tongue position or posture. PMID- 2316900 TI - Load-deflection rate measurements of activated open and closed coil springs. AB - The purpose of this investigation was to provide load-deflection rate data for a variety of open and closed coil springs. Ten millimeter lengths of open and closed coil stainless steel and Cobalt-Chromium-Nickel (Co-Cr-Ni) alloys in combinations of 0.008, 0.009 and 0.010 inch wire sizes, and 0.030 and 0.032 inch lumen sizes were tested. Other groups included heat treated Co-Cr-Ni springs and springs of 15 and 20 millimeter lengths. Forces and activations were measured by a tension load cell with an Instron universal testing instrument. Stiffness increased dramatically with wire size and pitch angle of the coils. Stiffness decreased slightly with increased lumen size. Co-Cr-Ni closed coil springs were slightly stiffer than stainless steel, whereas stainless steel open coil springs were much stiffer than Co-Cr-Ni. Heat treatment increased the stiffness of Co-Cr Ni coil springs. The length of the spring had a great effect on the load deflection rate. A shorter spring is stiffer than a longer spring by an amount directly proportional to the ratio of the length of the longer spring to that of the shorter spring. PMID- 2316901 TI - The orthodontic examination. PMID- 2316902 TI - Israeli cephalometric standards compared to Downs and Steiner analyses. AB - A sample consisting of 40 young Israeli adolescents, 18 males and 22 females, was examined cephalometrically. The subjects were classified as Angle Class I, with less than three millimeters of crowding and an orthognathic profile. Steiner and Downs analyses were performed for all subjects. Each analysis was done both manually and by using a computer. The computerized results were processed and subjected to statistical tests. The Israeli sample is characterized by a convex profile, a retrusive mandible, a steep mandibular plane and protrusive incisors. PMID- 2316903 TI - "Wits" appraisal in southern Chinese children. AB - The sagittal difference between the maxillary and mandibular apical bases in orthodontic diagnosis and treatment planning can be evaluated by means of the angle ANB or alternatively, by means of the "Wits" appraisal. The lateral cephalometric radiographs of a randomly selected sample of 101 Southern Chinese children aged 10-15 years, with 55 males and 46 females were traced and analyzed by the standardized method taught to dental undergraduates. The "Wits" appraisal and angulation of the A-B line to the functional occlusal plane were added in order to generate data relevant to the local population, on whom the flatness of the nose-nasion-forehead region imposes a genuine difficulty in the identification of the cephalometric nasion. Data analyses were performed under landmark nasion. Data analyses were performed under different categories with respect to age groups, 10-12 years and 13-15 years; the types of malocclusion and sex. It was found that both the angular and linear measurements were comparable to the existing norms established for the Chinese population. The "Wits" appraisal values have to be modified in order to be applicable to this population with -4.9 millimeters and -4.5 millimeters being the normal values for male and female children respectively. PMID- 2316904 TI - The morphology of canines in relation to preadjusted appliances. AB - The canine occupies the transition from anterior to posterior occlusion. Following orthodontic treatment the canine's incisal edge occlusion demonstrates the tip and torque present in the appliance that was used. The effective torque of the bracket, however, is influenced by the tooth morphology at the bracket's base. The morphology of the facial surface can be described by an angle formed between the tangent at the point of bracket placement and the long axis of the crown. In this study, tangent angles at four millimeters and five millimeters from the cusp tip of 100 maxillary and 70 mandibular canines were determined. There was a significant difference between tangent angles at the same location on different canine teeth and also at different locations on the same canine tooth. Proximal collum angles were also measured in this study and there was a significant negative proximal collum angle in maxillary canines and a significant positive proximal collum angle in mandibular canines. The presence of these normal biologic variables will either enhance or minimize the torque supplied by preadjusted appliances, depending on a combination of prescription used and biologic variable present. PMID- 2316905 TI - Hemifacial microsomia label questioned. PMID- 2316906 TI - The relationship between bite depth and incisor angular change. AB - A geometric, two-dimensional model was developed, which estimates the effect of changing incisal angular position to the effective bite depth. Because of the constant lengths of incisors whose long axes can be viewed as the sides of a triangle, it is possible to calculate the amount of their overlap as a function of changing angle. Additionally, a distinction is made between controlled and uncontrolled tipping, defined in respect to their centers of rotation. It is suggested that an average of 0.1 to 0.2 millimeter change in overbite occurs for every degree of incisal angular change. PMID- 2316907 TI - A new cephalometric parameter to aid in dental base relationship analysis. AB - The cephalometric literature is rich with different craniofacial analyses. However, since these analyses are only descriptive for the clear skeletal discrepancies and somewhat handicapped for borderline cases, an investigation was designed to assess the dental base relationship in the human lateral skull cephalostat radiograph. A number of existing measurements were reviewed, and a new measurement, based upon anatomical points which could prove to be more reliable, was introduced. PMID- 2316908 TI - Case report BC. Early identification and correction of transposed teeth. PMID- 2316909 TI - Adherence of Mycoplasma hyopneumoniae to cell monolayers. AB - This work was an attempt to develop an in vitro adherence model for Mycoplasma hyopneumoniae, using monolayers of human and porcine lung fibroblasts and porcine kidney cells. Mycoplasma hyopneumoniae grown in Friis mycoplasma broth was radiolabeled with 35[S]-methionine, washed, concentrated, and inoculated on the monolayers. After 15 minutes of centrifugation to facilitate adherence, monolayers were washed 3 times, dissolved with 0.1N NaOH, and suspended in scintillation liquid, and the radioactivity was determined in a liquid scintillation counter. Adherence, measured as a percentage of counts added, varied according to the mycoplasma strain and the cell line used. Comparison of strains J, 144L, and 232 of M hyopneumoniae revealed 7.5 +/- 5.9, 31.9 +/- 13, and 9.6 +/- 5% adherence to porcine kidney cells, respectively. Slightly different, but proportionally the same relationships were obtained with swine or human fibroblasts. Adherence was decreased slightly by repeated washings of the mycoplasma-treated cell monolayers; however, a plateau was reached, indicating irreversibility of the adherence process. Pretreatment of cell monolayers with nonlabeled organisms substantially blocked adherence by labeled organisms. Dilution of labeled organisms resulted in an increased proportion adhering. Therefore, it appears that the adherence was a receptor-dependent event. Treatment of the mycoplasmas with trypsin prior to the inoculation of monolayers resulted in a marked reduction in adherence. Treatment of the mycoplasmas with hyperimmune swine serum against M hyopneumoniae or normal swine serum resulted in 80 to 90% reduction of adherence; however, no inhibition occurred when mycoplasmas were treated with purified IgG from the hyperimmune serum. PMID- 2316910 TI - Excretion of porcine parvovirus through the genital tract of boars. AB - The putative binding of porcine parvovirus (PPV) to semen components in vitro was examined along with the shedding pattern of PPV in oronasally infected boars. Porcine parvovirus DNA was determined to be bound to spermatozoa that had been incubated in vitro with PPV and washed to remove loosely adherent virus. To determine whether PPV was shed in the semen, four 8-month-old boars, seronegative for PPV, were inoculated oronasally with a virulent strain of PPV. Prior to virus inoculation, a catheter was surgically implanted in the vas deferens for the purpose of collecting cauda epididymal semen free of extrinsic contamination. Epididymal semen specimens were collected prior to inoculation and daily thereafter for 21 days. A fifth boar was inoculated oronasally with PPV, but semen was collected by electroejaculation twice weekly for an equal period of time. Reproductive glands and semen specimens from all boars were examined by nucleic acid hybridization for the presence of viral DNA. All boars seroconverted to PPV, as evidenced by serum antibody titers ranging from 512 to 8,192 hemagglutinating inhibition units/50 microliters. Porcine parvovirus DNA was detected in epididymal semen of 3 of 4 catheterized boars on postinoculation days 5 through 9, but not in semen obtained by electroejaculation. Viral DNA was consistently detected in tissue samples collected on postinoculation days 8 and 21 from the scrotal lymph nodes (4 of 5 boars) and epididymides (3 of 5 boars). PMID- 2316911 TI - Pharmacokinetics of phenylbutazone given intravenously or orally in mature Holstein bulls. AB - Six mature Holstein bulls were each given 10 mg of phenylbutazone (PBZ)/kg of body weight, PO. Of the 6 bulls, 3 were given 10 mg of PBZ/kg by rapid IV administration 4 weeks later. Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling (sum of exponential functions). The harmonic mean of the biologic half-life of PBZ was 62.6 +/- 12.9 hours after oral administration and 61.6 +/- 7.2 hours after IV administration. The mean residence time was 94.61 +/- 8.44 hours and 90.49 +/- 8.93 hours for oral and IV administration, respectively. The mean total body clearance was 0.0015 +/- 0.0003 L/h/kg, with the mean apparent volume of distribution 0.134 +/- 0.021 L/kg. Mean bioavailability was 73 +/- 2% after oral administration. Phenylbutazone was adequately absorbed from the gastrointestinal tract in bulls. The apparent volume of distribution was small, indicating that PBZ distributed mainly into plasma and extracellular fluid. The total body clearance was also small, which accounted for the long half-life of PBZ in bulls. PMID- 2316912 TI - Pharmacokinetics of phenylbutazone in mature Holstein bulls: steady-state kinetics after multiple oral dosing. AB - Six mature Holstein bulls were given an 8-day course of phenylbutazone (PBZ) orally (loading dose, 12 mg of PBZ/kg of body weight and 7 maintenance doses of 6 mg of PBZ/kg, q 24 h). Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling. The harmonic mean +/- pseudo-SD of the biologic half-life of PBZ was 61.8 +/- 12.8 hours. The arithmetic mean +/- SEM of the total body clearance and apparent volume of distribution were 0.0021 +/- 0.0001 L/h/kg and 0.201 +/- 0.009 L/kg, respectively. The predicted mean minimal plasma concentration of PBZ with this dosage regimen was 75.06 +/- 4.05 micrograms/ml. The predicted minimal plasma drug concentration was compared with the observed minimal plasma drug concentration in another group of bulls treated with PBZ for at least 60 days. Sixteen mature Holstein bulls were given approximately 6 mg of PBZ/kg, PO, daily for various musculoskeletal disorders. The mean observed minimal plasma concentration of PBZ in the 16 bulls was 76.10 +/- 2.04 micrograms/ml, whereas the mean predicted minimal plasma concentration was 74.69 +/- 3.10 micrograms/ml. Dosages of 4 to 6 mg of PBZ/kg, q 24 h, or 10 to 14 mg of PBZ/kg, q 48 h, provided therapeutic plasma concentrations of PBZ with minimal steady-state concentrations between 50 and 70 micrograms/ml. PMID- 2316913 TI - Topically applied benzathine cloxacillin for treatment of experimentally induced infectious bovine keratoconjunctivitis. AB - The efficacy of an ophthalmic ointment containing benzathine cloxacillin for treatment of infectious bovine keratoconjunctivitis was determined in 2 experiments. In the first experiment, Holstein calves (n = 6/group) were inoculated with Moraxella bovis and treated on postinoculation days 3 and 6 with either topically applied benzathine cloxacillin (250 mg/eye) or long-acting oxytetracycline formulation (20 mg/kg of body weight, IM). A third group of inoculated calves remained untreated as controls. For the second experiment, 4 groups of calves (n = 6/group) were inoculated and treated on postinoculation days 3 and 6 with 50, 125, 250, or 375 mg of benzathine cloxacillin; a fifth untreated group served as controls. Ocular specimens were obtained for microbiologic culture, and eyes were observed and assigned a clinical score daily. Eyes were photographed on alternate days. Ulcer surface area was measured, using a planimeter. In experiment 1, the week-2 ulcer surface area measurements for both groups of treated calves were smaller than those for controls. There was a greater frequency of M bovis isolation from the ocular secretions of controls than from those of benzathine cloxacillin-treated calves during postinoculation weeks 2 and 3. The number of M bovis isolations from the benzathine cloxacillin- and oxytetracycline-treated calves was not significantly different at any sample collection interval. On week 3, the scores of the benzathine cloxacillin-treated calves were smaller than those of controls. In experiment 2, calves of the 250- and 375-mg groups had smaller ulcer surface area measurements than did controls on week 2. By week 3, calves of the 375-mg group had smaller scores than did controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316914 TI - Ocular and serum disposition kinetics of cloxacillin after topical administration of benzathine cloxacillin and intravenous administration of sodium cloxacillin to calves. AB - Disposition kinetics of cloxacillin were examined in calves after topical administration of benzathine cloxacillin and single IV administration of sodium cloxacillin, and the susceptibility of 17 field isolates of Moraxella bovis was measured. For the IV pharmacokinetic phase, sodium cloxacillin was administered at dosage of 10 mg/kg of body weight to male Holstein calves (n = 6, weighing 146 to 170 kg), and serum concentration of cloxacillin was measured thereafter for 10 hours. For the ocular pharmacokinetic phase, 6 calves were given either of 4 benzathine cloxacillin topical formulations consisting of 50-, 125-, 250-, or 375 mg doses. Treatment was repeated every 10 days until all 4 benzathine cloxacillin dosages were tested in the same 6 calves. Blood and tears were collected for 72 hours after each benzathine cloxacillin formulation was administered, and the concentration of cloxacillin in each specimen was measured, using a bioassay. The minimal inhibitory concentration of cloxacillin for 17 field isolates of M bovis was determined by use of an agar pour-plate dilution assay. After single IV administration of sodium cloxacillin, its half-life, body clearance, and volume of distribution were 19.5 +/- 12.8 minutes, 18.3 +/- 2.2 ml/min.kg, and 496 +/- 290 ml/kg, respectively. After topical administration of benzathine cloxacillin, cloxacillin concentration in lacrimal fluid peaked between 30 and 45 minutes and ranged between 963 micrograms/ml and 3,256 micrograms/ml for the 125- and 375-mg doses, respectively. There was no detectable cloxacillin activity in the lacrimal fluid of any calf by 36 hours after topical administration of benzathine cloxacillin, and cloxacillin was not detected in the serum at any time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316915 TI - Pharmacokinetic and tissue residue characteristics of fenprostalene, a prostaglandin F2 alpha analog, in swine. AB - Fenprostalene, a prostaglandin F2 alpha analog, can be used to induce parturition in swine. As part of the approval process for that indication, pharmacokinetic characteristics of the absorption and elimination of fenprostalene and the depletion of drug residues from the principal edible tissues of swine were studied. Blood samples, urine, and feces were collected from 8 gilts (body weight, 95 +/- 1.7 kg) for up to 72 hours after a single dose of 0.5 mg of 13,14 [3H]-fenprostalene in polyethylene glycol-400 was administered SC. At intervals of 24, 48, 72, and 168 hours after dosing, 2 gilts each were killed, and samples of liver, kidney, muscle, and abdominal fat were obtained for analysis. The mean (+/- SEM) maximal concentration of fenprostalene radioequivalents in plasma (0.41 +/- 0.05 nanogram-equivalents/ml; n = 8) was observed at 12 hours and decreased biexponentially, with half-lives of approximately 8 hours and 9 days. Mean cumulative recovery (n = 4) of the administered dose by 72 hours was 61.2 +/- 5.9% in urine and 18.5 +/- 2.6% in feces. The highest tissue fenprostalene concentration was in kidneys and liver, probably reflecting the role of those organs in excreting fenprostalene. Rates of depletion of fenprostalene equivalents from the injection site, kidneys, and liver were comparable with those previously observed in cattle. The composition of residue in the liver of 2 gilts slaughtered 12 hours after SC administration of [3H]-fenprostalene was examined in a second study. Results suggested that approximately 4% of the total residue was pharmacologically potent fenprostalene or the carboxylic acid form of fenprostalene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316916 TI - Correlation between drug and metabolite concentrations in plasma and anesthetic action of ketamine in swine. AB - Pharmacokinetic variables and metabolism of IM and IV administered ketamine (15 mg/kg of body weight) were determined in 8 swine (2 adult sows and 6 young pigs). After IM administration, maximal plasma concentration was rapidly reached, but peak concentration varied considerably, although comparison with IV data for the same swine indicated that the drug was almost completely absorbed from the musculature. After IV administration, ketamine kinetics followed a 3-term exponential decrease, indicating rapid initial distribution of the drug to highly vascular tissues including the brain, followed by redistribution into less vascular tissues, and elimination. Redistribution and elimination phases, with similar kinetics as those observed in the IV experiment, also were determined in the IM experiment. After both routes of administration, onset of anesthesia was rapid, and most swine recovered consciousness during the phase of redistribution, indicating that anesthesia is terminated by redistribution of drug from the brain into other tissues, whereas metabolism and excretion are less important for duration of anesthesia induced by ketamine. The time during which the swine resumed a lateral position (sleep time) was positively correlated with plasma ketamine concentration at onset of lateral recumbency, as well as with the area under the plasma concentration-time curve. The minimal plasma ketamine concentration for induction of immobilization was about 2 micrograms/ml. In adult sows, ketamine induced profound analgesia, which was not obtained in young pigs; this difference in potency could not be related to pharmacokinetic differences between young and adult swine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316917 TI - Pharmacokinetics, inhibition of lymphoblast transformation, and toxicity of cyclosporine in clinically normal pigs. AB - Pharmacokinetic variables were calculated from time-concentration data obtained after IV (10 mg/kg of body weight; n =9) and oral (12.5 mg/kg to group A [n = 3]; 25 mg/kg to group B [n = 3]; and 50 mg/kg to group C [n = 3] pigs) cyclosporine (formerly, cyclosporine A) administration. Resulting mean (+/- SD) pharmacokinetic variables were as follows: half life of distribution, 0.96 (+/- 0.7) hours; half life of elimination, 7.71 (+/- 2.6) hours; volume of distribution at steady state, 4.47 (+/- 2.22) L/kg; volume of the central compartment, 1.71 (+/- 0.78) L/kg; and systemic clearance, 8.95 (+/- 2.7) ml/kg/min. Oral bioavailability was: overall 57 (+/- 19) %; group A, 44 (+/- 11) %; group B, 78 (+/- 15) %; group C, 48 (+/- 6) %. Time to peak concentration was 3.55 (+/- 0.88) hours. During the 22 days of daily oral cyclosporine administration, blood 24-hour trough concentrations were: group A, 224.3 (+/- 78.4) ng/ml; group B, 640.7 (+/- 174.6) ng/ml; and group C, 2,344 (+/- 1,095) ng/ml. Lymphoblast transformation stimulation index was suppressed in all pigs except 1, which had a corresponding cyclosporine concentration of 92.4 ng/ml. Minimal, although statistically significant, decreases in serum albumin and magnesium concentrations and increases in serum creatinine and urea nitrogen concentrations were evident in pigs of some treatment groups. Histologic examination of necropsy specimens revealed mild hepatic necrosis (n = 1 pig), renal tubular dilatation (n = 5), and pulmonary inflammation (n = 2). Pigs given 25 and 50 mg of cyclosporine/kg failed to gain weight. PMID- 2316918 TI - Adverse effects of gentamicin in scarlet macaws and galahs. AB - The adverse effects of administration of gentamicin (5 mg/kg of body weight, IM, q 12 h) for 7 days were studied in healthy scarlet macaws (Ara macao) and galahs (Eolophus roseicapillus; cockatoos). Polydipsia and polyuria developed in each species, but were greater and persisted longer in the cockatoos. Peak water intake in the cockatoos more than quadrupled, and remained increased for 23 days after cessation of gentamicin administration. Plasma aspartate transaminase activity increased significantly (P less than 0.05) after treatment in the macaws, and plasma aspartate transaminase and lactate dehydrogenase activities increased in the cockatoos. Single IM administration of gentamicin (5 mg/kg) resulted in mean (+/- SEM) plasma concentration of 20.6 (+/- 1.85) micrograms/ml at 0.5 hour for either species of birds. There were no significant differences between mean plasma gentamicin concentrations for cockatoos and macaws at any time after drug administration, except at 12 hours, when values for cockatoos were significantly (P less than 0.05) greater than those for macaws. The elimination half-life for gentamicin after IM administration of 5 and 10 mg/kg was 1.17 and 1.07 hours, respectively, for macaws and 1.23 and 1.44 hours, respectively, for cockatoos. Correlation between drug disposition and adverse side effects could not be detected. PMID- 2316920 TI - Urinary indices of renal function in sheep with induced aminoglycoside nephrotoxicosis. AB - Aminoglycoside nephrotoxicosis (AGNT) was induced in ewes by daily SC administration of gentamicin. Changes in urinary indices of renal function during the development of AGNT are reported. Measurements from timed, volume-measured urine samples were made on days 0, 7, and 8 and included creatinine clearance, total excretion (TE) rates of electrolytes (Na, K, Cl, P) and urine volume. Measurements from free-catch urine samples (without volume measurement) were made daily and included fractional excretion (FE) rate of electrolytes, urine osmolality, and urine-to-serum osmolality and urine-to-serum creatinine ratios. With the onset of AGNT, FE rates of Na, K, Cl, and P- increased many fold above baseline values (200x, 4 to 5x, 6 to 9x, and 70 to 95x, respectively, on days 7 and 8), indicating decreased tubular reabsorption or increased tubular secretion. The increased FE rates were not representative of increases in total electrolyte excretion rates. The total excretion of Na (TENa) was mildly increased, TEK was decreased, TECl was unchanged, and TEP was significantly increased on days 7 and 8. Abnormal urinalysis results, glucosuria, and increased FEP preceded appreciable increase in serum creatinine concentration. Other abnormal urinary indices of renal function coincided with or followed the increase in serum creatinine concentration. Urinary indices may help characterize renal function associated with the disease state, but did not provide early indication of AGNT. PMID- 2316919 TI - Reference ranges and the influence of age and sex on hematologic and serum biochemical values in donkeys (Equus asinus). AB - Hematologic and serum biochemical values were determined in blood samples from 217 donkeys (Equus asinus). Donkeys were classified on the basis of size, sex, age, and whether they were domestic or feral. Parametric (mean +/- 2 SD) and nonparametric (2.5th to 97.5th percentile) reference ranges were calculated for each analyte. For all donkeys, 26 of 46 analytes significantly departed from gaussian distribution. Serum lactate dehydrogenase activity in miniature donkeys was higher than that in other donkeys. Differential leukocyte counts in feral donkeys differed from those in other types in ways that suggested that the former had smaller parasite loads or experienced greater stress. Erythrocyte, lymphocyte, and platelet counts and fibrinogen, glucose, inorganic phosphorus, and potassium concentrations decreased with age. Eosinophil counts, mean corpuscular volume, and plasma protein, serum protein, and serum globulin concentrations increased with age. Female donkeys had significantly (P less than 0.05) higher mean corpuscular hemoglobin concentration and leukocyte and neutrophil counts than did male donkeys. Mean corpuscular hemoglobin increased with age, and females had higher values than did males of all age groups. An interaction between age and sex was observed for alkaline phosphatase activity, with a trend for decreased activity with age. PMID- 2316921 TI - Effect of Pasteurella haemolytica-derived endotoxin on pulmonary structure and function in calves. AB - The role of endotoxin in the pathogenesis of acute pneumonic pasteurellosis is uncertain. Recently, we reported that Escherichia coli-derived endotoxin given by airway inoculation fails to induce lung injury in calves. Because Pasteurella haemolytica-derived endotoxin may differ substantially from E coli in its pathogenicity, we repeated these studies with Pasteurella endotoxin. Intratracheal inoculation of P haemolytica endotoxin caused hypoxemia and increased the alveolar-arterial oxygen differences without causing hypercarbia or changes in lung mechanical properties and volumes. In contrast, IV inoculation of endotoxin caused systemic hypotension, leukopenia, gas exchange impairment, increased total pulmonary resistance, and decreased dynamic compliance. Both routes of inoculation increased serum endotoxin concentrations and were associated with areas of pulmonary hemorrhage, edema, and acute inflammation. We concluded that P haemolytica-derived endotoxin is pathogenic by IV and airway routes of inoculation, and therefore differs from E coli endotoxin in its ability to induce lung lesions in calves. PMID- 2316923 TI - Histomorphometric comparison of measurements of trabecular bone remodeling in iliac crest biopsy sites and lumbar vertebrae in cats. AB - Trabecular bone remodeling values of the right and left iliac crest and lumbar vertebrae in cats were quantitated histomorphometrically and were compared. Healthy cats were given calcein (n = 2) or oxytetracycline (n = 2) twice for double-labeling of bone. Static and dynamic variables of bone resorption and formation were determined. Bone remodeling variables between right and left iliac crest were not significantly different (P less than 0.05). Significant differences (P less than or equal to 0.05) were not detected between values of iliac crest and lumbar vertebrae except in the percentage of osteoid surface. Percentage of osteoid surface was significantly (P less than or equal to 0.05) increased in the iliac crest compared with that in the vertebral body. Although not significantly different, values for bone formation were generally greater in the iliac crest than in the vertebral body. In healthy cats, values of trabecular bone remodeling were comparable between right and left iliac crest, and also were comparable between iliac crests and lumbar vertebrae. PMID- 2316924 TI - Effect of administration of prostaglandin F2 alpha on embryo recovery from the uterus on day 5 after ovulation in mares. AB - Ten mares were used to investigate the effect of administration of prostaglandin F2 alpha on uterine tubal motility, as reflected by embryo recovery from the uterus 5 days after ovulation (day 0). Mares were assigned to 3 groups: group A, uterine flush for embryo recovery on day 7; group B, uterine flush for embryo recovery on day 5; and group C, uterine flush for embryo recovery on day 5, after treatment with prostaglandin F2 alpha (10 mg, IM) on day 3. Each mare was assigned to each group once. Embryo recovery rates for the 3 groups were: A, 6 of 10; B, 2 of 8; and C, 0 of 10. The embryo recovery rate for group C was significantly lower (P less than 0.01) than that for group A. Embryo recovery rate for group B was not significantly different from group A or group C. Administration of prostaglandin on day 3 did not increase embryo recovery rate from the uterus on day 5. Additionally, the 25% embryo recovery rate (2 of 8) for group B mares suggested an earlier time for entry of the embryo into the uterus than has previously been reported. PMID- 2316922 TI - Suspected ciliary dysfunction in Chinese Shar Pei pups with pneumonia. AB - Chronic pneumonia was investigated in a litter of young Chinese Shar Pei in which 4 of 6 dogs were affected. Serum immunoglobulin concentrations (IgA, IgG, IgM) determined by radial immunodiffusion varied over time, but were not consistently lower in affected dogs, compared with control dogs. Two dogs that died had hydrocephalus and lymphoid depletion, in addition to severe broncho-pneumonia. Evaluation of ciliary ultrastructure in 2 affected dogs revealed random orientation of adjacent respiratory tract or oviductal cilia and a greater number of microtubular disarrangements, compared with control dogs. In vivo tracheal mucociliary clearance of 99mtechnetium macroaggregated albumin was absent in 1 dog examined. The ciliary abnormalities were suspected to have resulted in an inefficient mucociliary transport system predisposing to the development of pneumonia. Further evaluation of 1 Chinese Shar Pei revealed lymphocyte mitogenesis results that were not consistently less than those of a control dog, normal total hemolytic complement values, and normal blood neutrophil chemotaxis. PMID- 2316926 TI - Effects of halothane and isoflurane on mean arterial blood pressure, heart rate, and respiratory rate in adult Pekin ducks. AB - Although the cardiovascular and respiratory effects of halothane and isoflurane have been documented in a variety of common mammalian laboratory animals, they have not been investigated in birds. In this study, the effects of halothane and isoflurane anesthesia on respiratory rate, heart rate, heart rhythm, and mean arterial pressure in adult Pekin ducks were evaluated. Both anesthetics significantly increased heart rate and depressed blood pressure and respiration. Halothane induced a more profound alteration in heart rate and respiratory rate. With the ducks under halothane anesthesia, abnormal cardiac rhythms included ventricular fibrillation, ventricular bigeminy, and multifocal ventricular rhythms. Other than cardiac tachycardia, isoflurane induced no changes in cardiac rhythm. PMID- 2316925 TI - Effects of age, sex, and body size on serum concentrations of thyroid and adrenocortical hormones in dogs. AB - Thyroxine (T4), 3,5,3'-triiodothyronine (T3), and cortisol frequently are quantified in canine serum or plasma samples to aid in the diagnosis of hypothyroidism, hypoadrenocorticism, and hyperadrenocorticism. Many laboratories have established reliable references values for concentrations of these hormones in blood of clinically normal animals. However, nonpathologic factors that affect thyroidal and adrenocortical secretion may lead to misinterpretation of test results when values for individual animals are compared with reference values. The objective of the study reported here was to identify effects of age, sex, and body size (ie, breed) on serum concentrations of T3, T4, and cortisol in dogs. Blood samples were collected from 1,074 healthy dogs, and serum concentrations of the iodothyronines and cortisol were evaluated for effects of breed/size, sex, and age. Mean (+/- SEM) serum concentration of T4 was greater in small (2.45 +/- 0.06 micrograms/dl)- than in medium (1.94 +/- 0.04 micrograms/dl)- or large (2.03 +/- 0.03 micrograms/dl)-breed dogs, the same in females (2.11 +/- 0.04 micrograms/dl) and males (2.08 +/- 0.04 micrograms/dl), and greater in nursing pups (3.04 +/- 0.05 micrograms/dl) than in weanling pups (1.94 +/- 0.05 micrograms/dl), rapidly growing dogs (1.95 +/- 0.04 micrograms/dl), and young adult (1.90 +/- 0.06 micrograms/dl), middle-aged adult (1.72 +/- 0.05 micrograms/dl), or old adult (1.50 +/- 0.05 micrograms/dl) dogs. Dogs greater than 6 years old had lower mean serum T4 concentration than did dogs of all other ages, except middle-aged adults. Mean serum T3 concentration in medium-sized dogs (1.00 +/- 0.01 ng/ml) was greater than that in small (0.90 +/- 0.01 ng/ml)- and large (0.88 +/- 0.01 ng/ml)-breed dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316927 TI - Use of multiallelic human DNA probes to detect polymorphisms in the porcine genome. AB - Two human variable-number tandem repeat probes, pYNH24 and pYNA23, were examined for their possible ability to detect polymorphisms in the porcine genome. Useful DNA polymorphisms were detected in the porcine species, using both probes. In addition, results of Southern blot analysis of these markers in family studies indicated that the genome fragments obey mendelian laws of inheritance. PMID- 2316928 TI - Effects of milbemycin oxime on adult hookworms in dogs with naturally acquired infections. AB - Previous work indicated that adult Ancylostoma caninum can be removed from experimentally infected dogs, using a formulation of milbemycin oxime at dosage of 0.5 mg/kg of body weight. To determine the efficacy of this treatment in dogs naturally infected with adult hookworms, 24 mixed-breed dogs with patent hookworm infections were purchased from an out-of-state vendor, and 6 male and 6 female dogs were assigned to either a control group or a group that would be treated. Dogs were treated 10 days after their arrival and were euthanatized 1 week after treatment. Beginning 3 days before treatment, fecal samples were collected daily from all dogs, and the number of Ancylostoma eggs per gram of dry weight of feces was determined from each sample. By 1 week after treatment, the mean number of eggs being passed by the treated dogs had dropped from 12,700 to 10 eggs/g of dried feces; there was no apparent change in fecal egg counts for dogs of the control group. At necropsy, the mean number of adult A caninum in dogs of the treated and control groups was 1.3 and 56, respectively; in these naturally infected dogs, efficacy of treatment was calculated to be 97.8%. The mean number of adult Trichuris vulpis recovered in dogs of the control and treated groups at necropsy was 24 and 0, respectively, which yielded treatment efficacy of 100%. Although Uncinaria stenocephala and Toxocara canis appeared also to be removed by use of this dosage, too few dogs were in the study to calculate meaningful efficacies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316929 TI - Diagnosis of nitrate toxicosis in cattle, using biological fluids and a rapid ion chromatographic method. AB - An ion chromatographic method was used to simultaneously determine nitrate and nitrite ions in biological samples. Ultrafiltration was used to produce a protein free filtrate. Chloride interferences were eliminated by precipitation as the silver salt. Detection limits and average recoveries were 0.5 mg/L and 102% for nitrate and 0.2 mg/L and 78% for nitrite, respectively. Nitrate concentration was 2.1 +/- 1.8 mg/L and 4.9 +/- 0.8 mg/L in serum and ocular fluid of healthy cattle, respectively; nitrite was not detected. A severe case of nitrate poisoning in cattle was described and used to study the concentrations of nitrate and nitrite in samples obtained under natural conditions. Nitrate concentration of acutely poisoned cattle was 35% lower in ocular fluid at 158.1 +/- 51.4 mg/L, than in serum at 256.3 +/- 113.4 mg/L. Nitrite was not detected, because of the long processing time (greater than 3 hours) required for samples obtained in the field. A gradual decrease in ocular fluid nitrate of 29.4% at 24 hours, 25.9% at 36 hours, 51.6% at 48 hours, and 73.2% at 60 hours was observed; however, concentrations remained diagnostically significant (73.2 mg/L) 60 hours after death. Twenty-four hours after poisoning, the serum nitrate concentration of severely ill (52.7 +/- 51.9 mg/L) and moderately affected (12.4 +/- 5.7 mg/L) cattle that survived was indicative of the severity of clinical signs previously observed. Nitrate in serum and ocular fluid was stable in samples stored for 24 hours at 23 C, 1 week at 4 C, and 1 month at -20 C. PMID- 2316930 TI - Evaluation of the occult blood test in screening for colorectal neoplasms. A prospective study using flexible endoscopy. AB - Survival rates from colorectal cancer will rise only when polyps and cancers are found at an earlier, curable stage. Consequently, the purpose of the present study was to compare the yield of colonic neoplasms from flexible sigmoidoscopy and colonoscopy with that from occult blood testing. Results from 474 flexible sigmoidoscopies and 1,115 colonoscopies were prospectively recorded during a four year study period. Colorectal polyps were found in 111 (23.4%) patients undergoing flexible sigmoidoscopy and 325 (29.1%) patients undergoing colonoscopy. Among the 436 patients with polyps, the occult blood test was negative in 282 (64.7%). Among the 51 patients with colorectal cancers, the occult blood test was negative in 20 (39.1%). Thus, testing for occult blood missed the majority of polyps and a large percentage of the carcinomas. These data indicate that lower gastrointestinal endoscopy is superior to occult blood testing as a screening test for detecting colorectal polyps or cancers. Furthermore, given the high incidence of neoplasia in this patient population, the authors suggest that colonoscopy become the screening test of choice for colorectal cancer. PMID- 2316931 TI - The effect of preoperative endoscopy on recurrence and survival following surgery for colorectal carcinoma. AB - Numerous studies have elucidated the benefits of endoscopy before surgery for carcinoma of the colon and rectum. In patients with known colon cancer, the incidence of synchronous colon cancers is 1.5 to 7.6 per cent and synchronous colon polyps is 25 to 40 per cent. Standard barium contrast studies are inferior to endoscopic examination in detecting these synchronous lesions. Endoscopy has been shown to alter the planned surgical procedure in 11 to 13 per cent of patients with colorectal cancer. Nevertheless, some authors avoid preoperative endoscopy because of concern that neoplastic cells may be seeded throughout the colon during the examination. They fear that manipulation of the tumor may promote hematogenous or lymphatic spread. Our study seeks to demonstrate whether this concern is valid by comparing rates of local recurrence, distant metastases, and survival between patients who have undergone preoperative endoscopy with those who have not. PMID- 2316932 TI - Microcomputer image processing in gastrointestinal endoscopy. AB - A computer-based system was developed to handle information and endoscopic images in a clinical setting. The system is based on an 80286 AT computer whose topology includes a 16-bit color image capture/display graphics adapter and a 256 gray scale 8-bit digital image analysis processor. Using its color capabilities, one may initiate a picture database of patient's endoscopic images, x rays, and relevant clinical data. The computer-based imaging system allows instant access to this information and minimizes subjective evaluation, improving comparison and follow-up of treatments in a more objective manner. The image analysis components permit digital characterization of lesions, which allows online measurements and image enhancement. This is a cost-effective method of handling information and images in the clinical setting, facilitating endoscopic management and follow-up of the patient with gastrointestinal disease, as well as an effective research and teaching tool. PMID- 2316934 TI - Combined endoscopic and surgical gastrostomy when percutaneous endoscopic gastrostomy is contraindicated. AB - The resurgence of enteral feeding, as both a more physiologic and cost-effective means of alimenting patients, has coincided with the increased popularity of endoscopically placed gastrostomies. Indeed, numerous retrospective studies have shown that percutaneous endoscopic gastrostomy (PEG) is superior to its surgical counterpart. There are, however, both absolute and relative contraindications to percutaneous placement. Reported here are three patients who were poor surgical candidates, yet had contraindications to percutaneous placement. Described is a method of combined endoscopic and surgical placement under local anesthesia used successfully in these patients. General anesthesia and laparotomy were not required. A 2-cm incision with endoscopic guidance was used and the gastrostomy was placed under direct vision and secured with a gastric purse string and sutured to the abdominal wall. There was no morbidity or mortality among the three cases reported. All gastrostomies were considered functional within 48 hrs. The authors feel this method is an excellent alternative when PEG is contraindicated. In addition, it may represent the safest and most effective method of gastrostomy placement in the majority of patients requiring a gastrostomy. PMID- 2316933 TI - Pathogenesis of complications of percutaneous endoscopic gastrostomy. A lesson in surgical principles. AB - In two comparable series of percutaneous endoscopic gastrostomy differing in only one technical detail, complications were significantly reduced by omitting traction on the gastrostomy tube to approximate the gastric to the abdominal wall. Radiologic studies show that traction shortened the tract (4.9 +/- 1.1 cm with traction, 11.6 +/- 2.3 cm without traction). In two patients with fasciitis, gross pericatheter leak of contrast into a short and patulous tract was observed. Tube extrusion and gastrointestinal bleeding from gastric ersion ulcers were eliminated when traction was not used. No peritonitis occurred as a result of not attempting to approximate the stomach to the abdominal wall. The data suggest that traction on the gastrostomy tube is not only unnecessary, but is the cause of many of the complications reported. PMID- 2316935 TI - A reproducible, safe jejunostomy replacement technique by a percutaneous endoscopic method. AB - Patients undergoing esophagogastrectomy for cancer often benefit from postoperative nutritional support and an operative jejunostomy is frequently placed at the time of surgery. If the original tube has been removed, replacement of this jejunostomy previously required repeat laparotomy. Described here is the technique of direct percutaneous endoscopic jejunostomy placement (PEJ) used in two such patients following esophagogastrectomy. This PEJ placement technique using a #16-Fr, Pezzer-type Ponsky tube is an easy, reproducible method for the replacement of an operative jejunostomy tube. The fibrosed tract between the abdominal wall and jejunum allows the safe performance of the procedure if one endoscopically identifies the site of operative insertion. PMID- 2316936 TI - Endoscopic Nd-YAG laser treatment of colorectal neoplasms. A four-year longitudinal study. AB - In order to gain a longitudinal perspective of the benefits, complications, and role of the neodymium yttrium aluminum garnet (Nd-YAG) laser in the treatment of colorectal neoplasms, we performed a review of endoscopies using the laser during a 53-month period ending in January 1989. We reviewed the records of 100 patients for details of the endoscopic procedure and demographic data. Performance status and survival were critically assessed. We performed 275 procedures on 57 men and 43 women with an average age of 76.5 years. An average of 2.75 procedures, each lasting an average of 45 minutes, were performed per patient. Half of the patients had fulgurations of rectal tumors with the common indication being bleeding. Thirteen morbid events and no deaths occurred. Ninety-six per cent of the procedures were performed with the patient under intravenous sedation. The Karnofsky performance scale applied to surviving patients revealed that 90 per cent were able to care for themselves and scored greater than 70. Average survival was 5.58 months. Our results indicate that the Nd-YAG is a safe and effective tool in the treatment of colorectal neoplasms offering palliation as well as maintenance of quality of life. PMID- 2316937 TI - Fibrosis of gastric cardia after endoscopic sclerosis. Mechanism for control of experimental reflux? AB - Endoscopic sclerosis of the gastric cardia (ESGC) prevents experimental gastroesophageal reflux (GER) without changes in lower esophageal sphincter (LES) pressure and length. This study was performed to define the histologic appearance of the esophagus and stomach one year after ESGC. Four dogs were studied one year after ESGC with morrhuate sodium; ESGC had been performed at six sites, 1-3 cm distal to the esophagogastric junction. All animals had stable weight and eating habits at sacrifice. Light microscopy of the cardia and LES included morphometry of wall thickness (mm) and assessment of fibrosis (- to ). The esophagus had minimal changes; the gastric cardia had focal fibrosis, maximal on the greater curve, without any change difference in wall thickness. ESGC results in fibrosis of the gastric cardia, without significant changes in the esophagus. These changes prevent GER, possibly by preventing the initiation of a reflux event. PMID- 2316938 TI - Strictures following gastric stapling for morbid obesity. Results of endoscopic dilatation. AB - Gastric-restrictive operations for the treatment of morbid obesity are well established. Postoperative stricture is one complication of this procedure. In a large obesity practice, 40 patients presented with this complication. The authors reviewed retrospectively the management of these strictures, using endoscopic dilatation. All patients were morbidly obese, defined as greater than 100 pounds more than ideal weight. The original gastric-restrictive procedure included vertical-banded gastroplasty (35 patients); revision vertical-banded gastroplasty (2 patients); and revision of gastric bypass to vertical-banded gastroplasty (3 patients). Three methods were used: dilatation with endoscope, balloon dilatation, and Savary-Guilliard dilatation. Twenty-seven patients became asymptomatic after dilatation (68%). Occasionally, multiple dilatations were necessary. In 13 patients (32%), dilatation was unsuccessful and revision surgery was needed. In early postoperative (6 to 12 weeks) stricture, dilatation with the endoscope was often successful. When strictures were associated with an angulated channel, dilatation was almost uniformly unsuccessful. In summary, endoscopic dilatation for postgastroplasty strictures is a useful and effective technique, obviating the need for operative revision in the majority of patients; however, when the stenosis is associated with channel angulation, dilatation is almost uniformly unsuccessful. Such patients should not be subjected to repeated dilatation but rather proceed promptly to revision surgery. PMID- 2316939 TI - Nodular duodenitis and single duodenal nodules. AB - Duodenal nodules are an uncommon endoscopic finding generally thought to indicate duodenal inflammation. This study examines the incidence and histologic correlates of multiple and single duodenal nodules in 2,966 consecutive male patients who underwent esophagogastroduodenoscopy during the past five years. Five per cent had duodenal nodules. When two or more discrete nodules, with or without apical ulceration, were present, the finding was termed nodular duodenitis, which was seen five and one-half times more frequently than single nodules. There were 127 patients with nodular duodenitis (4.3%); seven had chronic renal disease and 33 (26%) had concomitant peptic ulcer disease. Biopsies showed either normal mucosa or histologic aberrations typical of nonspecific duodenitis. Single nodules were seen in only 23 patients (0.8%). Biopsies of these nodules revealed benign or malignant tumors in five instances and infrequently showed only normal mucosa. It is concluded that nodular duodenitis is a visually distinct, morphologic variant of nonspecific duodenitis bearing some yet-to-be-defined relationship to peptic ulcer disease. Single nodules are much less likely to represent duodenitis and, in fact, they have significant neoplastic potential, mandating biopsy whenever they are found. PMID- 2316940 TI - Intraoperative flexible videocholedochoscopy. An improved technique for evaluating the common duct. AB - At the conclusion of common duct exploration, a T-tube cholangiogram is usually performed. Recently, flexible choledochoscopy has become available to evaluate the interior of the common duct. We compared four cases, using the videocholedochoscope with completion T-tube cholangiography, both in our four patients and historically. We used the Olympus CHF-P20 flexible choledochoscope, which is 4.8 mm in diameter, hooked to an Olympus S-4 videoadapter. We found that flexible choledochoscopy enabled us to evaluate the biliary tree directly from the ampulla to the third branch radicle within the liver. In all cases, the common ducts were normal after stone removal. Both the preexploration and completion T-tube cholangiograms yielded less information. We conclude that flexible choledochoscopy is an improved technique that allows a more thorough evaluation of the common duct, obviates more extensive procedures, i.e., sphincteroplasty, by removing stones through the scope, and negates the need for a completion T-tube cholangiogram. We encourage all biliary tract surgeons to consider this technique for their own use. PMID- 2316941 TI - Endoscopic retrograde cholangiopancreatography in a general surgery practice. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is performed for the diagnosis and therapy of benign and malignant biliary and pancreatic disease. There are few reports in the literature regarding the incorporation of this procedure into a general surgery practice. One hundred seven consecutive ERCPs performed by the same surgeon over a two-year period were reviewed. The most frequent indications for ERCP were jaundice, suspected common bile duct stones, and a history of pancreatitis. Successful cannulation of the ampulla of Vater was achieved in 97 per cent of the cases with the desired duct being adequately visualized in 90 per cent of the cases. Sphincterotomy was performed in 42 per cent of the procedures and common bile duct stones were removed with a balloon or basket catheter. The overall complication rate was seven per cent with no mortality. ERCP accounted for 20 per cent of all endoscopies and 12 per cent of all procedures performed by the surgeon. Twelve per cent of these patients were subsequently operated upon by the surgeon while another 16 per cent requiring surgery were returned to the referring physician. This study supports the feasibility of the incorporation of ERCP into a general surgery practice. PMID- 2316942 TI - Partner notification: can it control epidemic syphilis? AB - STUDY OBJECTIVE: During 1987, the rate of syphilis among heterosexual adults in Oregon increased 159%, yet the number of cases of gonorrhea remained stable. Our study was done to evaluate why the same control measures contained gonorrhea but not syphilis in this population. DESIGN: Exploratory case-control study. SETTING: Public health clinics in Portland, and Salem, Oregon. PATIENTS: All 146 heterosexual adults with early syphilis and all 164 heterosexual adults with acute gonorrhea reported to the public health clinics during April to July 1988. INTERVENTION: A questionnaire was administered to all syphilis case-patients and control patients (those with gonorrhea) at the beginning of the routine, sexually transmitted disease (STD), investigative interview. MEASUREMENTS AND MAIN RESULTS: Syphilis case-patients had contact with an average of 5.0 sex partners for whom they could not supply locating information sufficient to initiate partner notification. In contrast, patients with gonorrhea had contact with an average of 0.4 sex partners for whom they could not supply locating information (P less than 0.005). The 28% (41 of 146) of syphilis case-patients who reported having exchanged sex for drugs or money accounted for 72% (527 of 729) of the unlocatable partners exposed to syphilis. In contrast, the 17% (28 of 164) of patients with gonorrhea who reported having exchanged sex for drugs or money accounted for 36% (25 of 69) of the unlocatable partners exposed to gonorrhea. CONCLUSIONS: Because patients infected with syphilis have relatively large numbers of anonymous sexual encounters, prevention strategies that supplement partner notification are urgently needed to control the syphilis epidemic among adults. PMID- 2316943 TI - The fat overload syndrome: successful treatment with plasma exchange. PMID- 2316945 TI - Lovastatin and hypospermia. PMID- 2316944 TI - Altitude hypoxemia and the arterial-to-alveolar oxygen ratio. PMID- 2316946 TI - Erythropoietin and anemia of gastrointestinal bleeding in a Jehovah's Witness. PMID- 2316947 TI - Anticonvulsants and busulfan. PMID- 2316948 TI - Parental leave. PMID- 2316949 TI - Planning parental leave. PMID- 2316950 TI - Endophthalmitis due to Mycobacterium avium in a patient with AIDS. AB - A 27-year-old man with acquired immunodeficiency syndrome [AIDS] had endophthalmitis OS four years after a trabeculectomy was done. The patient had a history of disseminated infection with Mycobacterium avium. Examination showed an intact filtering bleb with inflammation and hypopyon formation in the anterior chamber OS. The M. avium was cultured from an anterior chamber paracentesis. The patient responded to treatment with gentamicin, cefazolin, and prednisolone. Infection with M. avium should be included in the differential diagnosis of endophthalmitis in patients with AIDS. PMID- 2316951 TI - Problems with current concepts of the epidemiology of Mooren's corneal ulcer. AB - Results from an analysis of 287 patients in 20 series do not support widely held concepts of the descriptive epidemiology of Mooren's corneal ulcer, i.e., that bilateral disease is more common in younger patients and blacks. Our review shows that the disease is reported 1.6 times more frequently in males than in females regardless of race or age. Black patients are five times more likely to be young than are white patients. However these figures may be misleading since they are not calculated from population-based estimates. Our analysis highlights misconceptions and emphasizes the hazards of drawing conclusions about the epidemiologic characteristics of this disease based on currently available data. PMID- 2316952 TI - Mooren's ulcer treated with a periosteal graft. AB - We report a case of recurrent Mooren's ulcer treated with an autogenous periosteal graft. The eye responded well to this therapy. Final visual acuity was 20/40 with spectacle correction of +2.00 + 2.50 X 165. PMID- 2316953 TI - Vogt-Koyanagi-Harada syndrome and pregnancy. AB - Two black women had bilateral anterior and posterior uveitis, nonrhegmatogenous retinal detachments, pleocytosis, headaches, dysacousis, and alopecia. These patients with Vogt-Koyanagi-Harada (VKH) syndrome improved clinically while they were pregnant after the discontinuation of corticosteroid treatment. They developed recurrent symptoms and findings after termination of their pregnancies. We speculate that changes in immunity and humoral constituents during pregnancy account for their remissions. It is important to assess the menstrual history and to avoid pregnancy before initiating steroid treatment for VKH syndrome. PMID- 2316955 TI - Optociliary shunts and sickle retinopathy in a woman with sickle cell trait. AB - We report a case of unilateral optociliary shunt vessels and sickle cell retinopathy in a patient with sickle cell trait. Sickle cell retinopathy has rarely been reported in patients with sickle cell trait hemoglobinopathy. To our knowledge, this is the first report of the association of sickle cell trait, unilateral sickle cell retinopathy, and ipsilateral optociliary shunt vessels. PMID- 2316954 TI - Immediate contralateral amaurosis after retrobulbar anesthesia. AB - Many potential complications associated with retrobulbar anesthesia have been reported. Of these, sudden loss of vision in the contralateral eye is the least expected. We report a case of immediate loss of vision in the fellow eye after retrobulbar anesthesia for cataract extraction. Possible etiology such as emboli thrown during ventricular fibrillation, direct optic nerve anesthetic injection with reflux to the chiasm, cortical stroke, amaurosis fugax, arterial injection of anesthetic material, and hysteric reaction are discussed. PMID- 2316956 TI - Is asteroid hyalosis ocular gout? AB - In 76 cases of asteroid hyalosis, seven (9.2%) had gout, eight (10.5%) had close relatives with gout, and two (2.6%) were in both categories. Three of the gouty seven were receiving gout medications. Serum uric acid measurements were elevated in 28.3% of the 46 cases (60.5%) measured. In the 68 monocular cases (89.5%), whites (57 cases) showed no right/left predilection, but blacks (11 cases) had 100% left eye involvement (P less than .001). From a review of 49,000 records, prevalence rates were calculated for discrete age and sex groups. Females under age 60 had no asteroid hyalosis. After age 60 they had a constant prevalence rate of one case per 600 (0.15%). Males of all ages had a higher prevalence rate than females, increasing with age to one per 126 (0.79%) in the 80-or-older group. In all 76 patients, the male-to-female ratio was 1.45:1. Among whites it was, 1.74:1, and among blacks, 0.63:1. PMID- 2316957 TI - [An example of detection of heterozygotes and antenatal diagnosis in four families with anhidrotic ectodermal dysplasia]. AB - Anhidrotic ectodermal dysplasia is an X-linked inherited skin disorder; only affected males exhibit the complete syndrome, whereas females may have a few mild features. The gene involved in this disease is located in the proximal area of the long arm of the X chromosome, in the q13 position. Molecular analysis is very helpful for calculating the risk of transmission in sisters with normal phenotypes and affected individuals (family 1 provides an example), but cannot solve all problems (example of family 4). The best results are obtained when there are two informative markers, each located on either side of and very close to the mutant gene. Molecular analysis can also be applied to chorionic villi sampled at the tenth week of gestation in order to achieve antenatal diagnosis in male fetuses in high risk families. Until recently, antenatal diagnosis could be performed only at the twentieth week of gestation by the demonstration of inadequate development of skin glands in skin biopsy specimens sampled under fetoscopy. Family 2 provides an example of antenatal diagnosis and highlights the risk of error that always exists in molecular analysis studies. PMID- 2316958 TI - [Nosocomial Staphylococcus epidermidis and Staphylococcus aureus septicemias in neonates]. AB - Sixteen neonates developed staphylococcal septicemia (S. epidermidis in 10 cases and S. aureus in six). Two infections were due to maternofetal contamination and four to contaminated foreign material. Clinical symptoms included non-specific evidence of neonatal bacterial infection and, in S. aureus infections, suggestive skin or bone localizations. Fifteen patients recovered without sequelae and one died as a result of S. aureus septicopyemia. In view of the patterns of resistance to antimicrobial agents exhibited by S. aureus and S. epidermidis, the vancomycin-amikacin combination seems the most appropriate treatment in neonatal staphylococcal septicemias. However, the fosfomycin-cefotaxim combination can be proposed for the treatment of staphylococcal infections with osteoarticular or meningeal involvement. PMID- 2316959 TI - [Failures observed after repair of the pyeloureteric junction in children based on a series of thirteen cases]. AB - We report a series of 13 infants with failed surgery for pyeloureteric junction (PUJ) obstruction. Failure was defined as the necessity for further surgery, either refashioning of the anastomosis or nephrectomy. These infants were part of a series of 306 with 322 PUJ. Of the 258 surgically treated infants, 232 (90%) had a post operative course without complication or need for reoperation. The failure rate was significantly higher in infants operated before the age of 4 months (8/65: 12.3%) when compared with those over 4 months of age (5/193: 2.59%). The use of postoperative drainage via a nephrostomy significantly reduced the percentage of early complications (e.g. fistula) but did not affect the final failure rate. The severity of the obstruction at presentation correlated with a bad outcome after reoperation. Of the cases which resulted in failure after reoperation (7/258: 2.7%) all occurred in cases of severe obstruction with parenchymal damage. While the failure of surgery is often evident early (persistant fistula, urinoma, non-functioning kidney on IVP) this may only become obvious some years later. Reoperations were successful in half the cases irrespective of the time between the initial operation and the reoperation. Long term follow-up of all infants operated for PUJ obstruction is recommended. PMID- 2316960 TI - [Ophthalmologic manifestations of the Pierre Robin syndrome. Report of a case of microphthalmia]. AB - The classical description of the Pierre Robin syndrome includes micrognathia, glossoptosis, airway obstruction, and usual presence of a cleft palate. The Pierre Robin syndrome is currently defined as the combination of retrognathia, cleft palate, and respiratory distress. This last is mixed, with a peripheral component due to glossoptosis and a central component due to brain stem immaturity. The main ocular manifestations found in the Pierre Robin syndrome are congenital glaucoma and severe congenital mypopia responsible for retinal detachment. Microphthalmia is infrequent. We report the case of a neonate with severe Pierre Robin syndrome and major microphthalmia documented by CT scan. PMID- 2316962 TI - [Torticollis in children: do not forget the Sandifer syndrome]. AB - We report a case of Sandifer syndrome with chronic torticollis and gastroesophageal reflux (GER). The infant exhibited regurgitations and vomiting from birth. Torticollis with a permanent tilt of the head towards the right developed at age six months. At 16 months, persistence of the vomiting and abnormal attitude of the head and neck led to a CT scan that outruled a brain tumor. Esophageal pH recordings disclosed severe gastroesophageal reflux (pH less than 4 for 46% of the time over 24 hours) and endoscopy showed ulcerated peptic esophagitis. Surgical treatment of the GER ensured both resolution of the reflux and disappearance of the torticollis, establishing the causal relationship between the former and latter manifestations. PMID- 2316961 TI - [Iatrogenic Cushing syndrome in infants. Report of a case with dwarfism]. AB - We report a case of iatrogenic Cushing syndrome with dwarfism (-6 SD) in an eight month-old infant. The respective role of exposure to corticosteroids in utero (the mother took 30 mg prednisolone per day throughout pregnancy) and postnatally (oral prednisolone, prednisolone in breast milk, and betamethasone cream) is discussed. Two other features are pointed out, i.e. presence of a food allergy and favorable outcome under hydrocortisone therapy. PMID- 2316963 TI - [Waardenburg syndrome. Report of a familial case]. AB - We report a familial case of Waardenburg syndrome. A four and a half year old boy had displacement of the canthi, a white forelock, perceptive deafness, and a congenital heart defect. The mother and younger brother had the same syndrome. Usually, cases of Waardenburg syndrome are divided into types I and II according to whether lateral displacement of the inner canthi is present or absent. Uni or bilateral perceptive deafness is found in 13 to 28% of type I cases and 53% of type II cases. The white forelock is a feature in 30% of cases and should suggest the diagnosis. Several other abnormalities have been reported in this syndrome. Inheritance of Waardenburg syndrome is autosomal dominant with variable penetrance. We discuss the possibility that one or both of the children we report were homozygous for a dominant gene. PMID- 2316964 TI - [Single preoperative intravenous dose of metronidazole for appendectomy in children]. AB - One hundred children were prophylactically treated with 15 mg/kg-1 of metronidazole immediately before appendicectomy and retrospectively compared with 100 other patients without any antibioprophylaxis. No statistically significant difference was found between the two groups as regards age, weight, sex and macroscopic appearance of the appendix. The overall incidence of complications was 1% in the antibioprophylactic group and 9% in the control group. Furthermore, a single pre-operative intravenous dose of metronidazole was as effective as conventional antibioprophylaxis. PMID- 2316965 TI - [Emotional attachment in children]. PMID- 2316966 TI - [International Convention on Children's Rights]. PMID- 2316967 TI - [Sudden infant death syndrome]. AB - Over the last 20 years, the sudden infant death syndrome has become the leading cause of death in infants aged one month to one year in developed countries. The SIDS Referral Centers set up in France have been assigned the task of performing thorough clinical, metabolic, infectious and histologic studies. This post-mortem evaluation, whose results are difficult to interpret, is undertaken in an attempt to discriminate between the multiple causes of conditions present at the time of death. This classification task will improve the definition of a number of risk factors. Among these factors, prematurity, perinatal distress requiring resuscitation, and an unfavorable sociocultural environment are often mentioned. Other factors, including intrauterine growth retardation, dysmorphic disorders, impaired regulation of ventilation, heart rhythm anomalies, and inherited defects in fatty acid metabolism are still under study since they are all infrequent. Various combinations of these factors may result in increased vulnerability to stress during the first months of life, the period when SIDS is most common. This ongoing research is indispensable for providing advice and support of the family and developing appropriate individual preventive measures for newborn SIDS siblings. PMID- 2316968 TI - Nonmicrosurgical transfer of the radial forearm flap for head and neck reconstruction. AB - In this article I present a nonmicrosurgical technique for transferring the radial forearm flap for reconstruction of defects in the head and neck. The technique is described briefly and experience with 7 patients is presented. The advantages of this method are discussed. PMID- 2316969 TI - Partial eyebrow reconstruction using subcutaneous pedicle flaps to preserve the natural hair direction. AB - Five cases of partial eyebrow reconstruction using subcutaneous pedicle flaps from the ipsilateral eyebrow are presented. Proper use of this method will enable safe one-stage transfer of the skin and the eyebrow hair, preserving the natural hair direction and properties. It will also leave minimal scars and dog-ears. This method is especially suitable for the reconstruction of moderate- to small sized eyebrow defects. PMID- 2316970 TI - Combined suction-assisted lipectomy, surgical lipectomy, and surgical abdominoplasty. AB - Although combined suction-assisted lipectomy (SAL) and surgical abdominoplasties have been described, the surgical excisions have in general been small and limited to the lower portion of the lower abdomen (i.e., just above the pubis). For the obese patient this is an insufficient lipectomy. SAL alone is unsatisfactory because the marked skin excess will not shrink sufficiently to allow a desired final result. Surgical abdominoplasty alone is also insufficient in the obese patient because the thickness of the abdominal panniculus is not reduced and, additionally, secondary to tissue tension with wound closure, some necrosis of skin above the pubis is not unusual. In this article results are described from a small consecutive series of obese patients treated with a combined extensive SAL, surgical lipectomy, and surgical abdominoplasty. The sequence of fat removal is different than that which has been previously described. In all of the patients the results were pleasing, and there were only two relatively minor complications. PMID- 2316971 TI - Use of cartilage graft for an orbital socket implant. AB - After enucleation, a spherical implant of some material is placed into the muscle cone to give bulk to the orbital socket area. This also allows better movement of the artificial eye prosthesis, which is placed in the socket to give the appearance of a normal eye. If there is loss of the spherical implant because of infection or extrusion for other reasons, there is a resulting enophthalmos of the prosthetic eye. Replacement of this spherical implant with another implant of alloplastic material often results in secondary extrusion. In other cases, there is downward displacement of the spherical implant with pressure against the prosthesis and lower lid. This causes undue stretching of the lower fornix and lid area with inability to hold the prosthesis in place. To correct these two problems, we have found that an autogenous cartilage graft is useful for an implant that will not extrude and that holds its position. Examples of this technique and preoperative and postoperative cases are described here. We have used this technique over the past 11 years and have achieved good success in 15 patients. PMID- 2316972 TI - Results of the Allen test on 2,940 arms. AB - The ulnar arterial circulation to bilateral hands of 683 men and 787 women was assessed with the Allen radial artery compression test. Of the 2,940 arms, the Allen test showed abnormalities in 105 (3.6%). The incidence of abnormality generally increased with age: 2.2% in the first decade and 6.9% after the ninth decade. It is very likely that circulatory failure in the hand develops after several decades among those whose radial artery was removed in their youth. When the radial artery is removed in the young, attention should therefore be paid to future consequences. PMID- 2316973 TI - The anatomy of the subscapular artery and its effects on flap design in the rabbit. AB - The course of the subscapular artery was studied in 20 rabbits. Its course was constant, giving two branches to the latissimus dorsi muscle after which the vessel sent a branch (S1) that perforated the panniculus carnosus to supply a large territory of skin. In a separate experiment, the contribution of the S1 branch to the viability of the rabbit latissimus dorsi musculocutaneous flap was evaluated. From this experiment it can be concluded that, first, it is possible in a rabbit to elevate a large skin flap based solely on a muscle perforator (S1), which survives completely. Second, in the rabbit latissimus dorsi musculocutaneous flap, S1 is the major blood supply to the skin component. Damage to it severely diminishes skin flap survival, even if the vascular supply to the underlying muscle is completely intact. PMID- 2316975 TI - Treatment of the concrete scalp donor site. AB - The scalp has become a popular donor site for split-thickness skin, and few complications have been reported. However, we have been troubled by 5 patients in whom the donor site did not epithelialize but rather turned into dried granulation tissue with embedded growing hairs, a situation rather like concrete with steel reinforcing rods. The pathophysiology is not clear but seems to be related to thick grafts from hair-bearing areas. We treated the lesions by removing the granulation tissue, shaving the hair, and treating the wound as a new donor site. Four lesions healed with total or near total regrowth of hair, and one required a small skin graft. PMID- 2316974 TI - Intraluminal cyclosporine A reduces capsular thickness around silicone implants in rats. AB - One theory of the cause of connective tissue capsule formation around silicone mammary prostheses is based on an immunological interaction. In an in vitro pilot study, it is shown that intraluminal cyclosporine A, a potent T-lymphocyte specific immunosuppressive agent, can diffuse slowly through the outer shell of a standard double-lumen silicone breast implant. Round silicone tissue expanders containing 50 mg of cyclosporine A were implanted subcutaneously in 10 rats. Ten animals served as controls. Evaluation was performed after three months. A significant decrease in collagen capsular thickness of 21.6 +/- 5.4 microns (mean +/- standard deviation was measured histomorphometrically in the treated group compared with 39.6 +/- 8.6 microns in the control group (p less than 0.001). PMID- 2316976 TI - Psychological considerations in the elderly cosmetic surgery candidate. AB - The mean age of Americans is increasing, and more and more Americans are living longer and more productively. It follows, therefore, that an increasing number of elderly patients will be seen by the cosmetic surgeon. These patients are often in the surgeon's office to negate or erase the physical effects of old age, which serve as social cues expressing inadequacy and inability. The plastic surgeon can "turn back the clock" as it relates to physical appearance for these patients; however, not every patient seen by the surgeon is an ideal candidate for surgery. Normally, the surgeon is used to dealing with the physical possibilities of surgical procedures and how they relate to surgical results, but what about the mental health of the elderly patient? In this article we seek to help the plastic surgeon identify the elderly patient who poses potential problems in the preoperative and postoperative periods because of inadequate or unstable mental health. PMID- 2316977 TI - Open reduction and interfragment wire fixation of comminuted nasal fractures. AB - Manual reduction is the first choice for all types of acute nasal fractures; open reduction is the choice for fractures that do not respond to manual reduction or complicated fractures at the base of the nasal pyramid. From 1968 to 1986, 564 cases of nasal fractures were treated at the Department of Plastic and Reconstructive Surgery, Jikei University School of Medicine, Tokyo. Of these, 241 were acute nasal fractures, 52 of which were associated with facial bone fractures. Deviated types of fractures that cannot be correctly repositioned by manual reduction and some depressed fractures often require a surgical approach for reduction and fixation. In our series of 241 patients with acute nasal fractures, 43 (18%) were treated by open reduction and fixed with soft stainless steel wires. PMID- 2316978 TI - Basal cell burn carcinoma. AB - Postburn malignant degeneration into squamous cell carcinoma is unusual but well described. Much rarer is malignant degeneration of a burn into basal cell carcinoma. Recently a well-documented case was seen. The cause was postulated to be injury to the more superficial hair follicles and sweat glands. A brief report is given. PMID- 2316979 TI - A better "sky hook" for hand elevation. PMID- 2316981 TI - Textured silicone and capsule contracture. AB - An experiment was performed in rabbits to test the effect of a textured surface of a silicone implant on the incidence and severity of capsule contracture. Contrary to the hypothesis of this experiment, texturing of the implant surface resulted in an increase in the contracture problem rather than a reduction. PMID- 2316980 TI - Simple suction drainage: an adjunct to septal surgery. AB - Postoperative hematoma is a complication of septal surgery that can be associated with significant morbidity and possibly even mortality in some cases. A simple suction drainage technique using a scalp vein cannula and vacuum tube can prevent a septal hematoma without the need for bulky nasal packing (with its attendant nasal obstruction and risk of bleeding on removal). The technique is also useful for postoperative drainage of an established septal hematoma or abscess secondary to trauma. PMID- 2316984 TI - The sliding plication gluteus maximus musculocutaneous flap for reconstruction of sacrococcygeal wounds. AB - The technique of the sliding gluteus maximus muscle flap as originally described has allowed closure of defects up to 20 cm in transverse diameter. However, this requires extensive dissection and mobilization of the musculocutaneous units. A modification of the original flap is described. In this technique, there is no subcutaneous dissection. The dissection is limited to the submuscular plane of the lower portions of the muscle origin. These modifications lessen the amount of dissection and blood loss and shorten the operative time. This had permitted closure of sacrococcygeal defects up to 12 cm in transverse diameter. Twenty-two patients with a variety of sacrococcygeal defects were successfully reconstructed with this technique. PMID- 2316982 TI - Submalar augmentation: a procedure to enhance rhytidectomy. AB - The use of submalar augmentation in facial rejuvenation surgery satisfies the need for enhancement of the midface to obtain longer lasting and better results from rhytidectomy. Submalar augmentation is a new surgical technique that positions anatomically designed silicone implants over the midthird of the face. It provides the appearance of restoring midfacial soft tissue and reduces the depth of anterior facial folds. The enhanced underlying bone structure avoids exerting excessive tension on the skin during face-lift surgery, thus preventing distortion of midfacial architecture. Submalar augmentation is a procedure that has been used as a supplementary enhancement to rhytidectomy in 56 patients over six and one-half years. Only minimal complications have been reported, all of which have been satisfactorily resolved. To date, no implant has been rejected or permanently removed. In our experience, when performed in conjunction with rhytidectomy, submalar augmentation has greatly enhanced and prolonged the results of face-lift surgery, and has significantly increased patient satisfaction. PMID- 2316983 TI - Washout of vessels with heparin does not improve patency following severe microarterial trauma: an experimental study. AB - The antithrombotic effect of heparin used as a wash-out solution in small arteries has been evaluated following severe vessel trauma (arteriotomy/intimectomy). Twenty-three central arteries of rabbit ears were prepared and platelets labeled with phosphorus-32 injected intraaortically. The arteries were positioned in double vascular clamps and opened by arteriotomy, and intimectomy was performed. After reestablishing blood flow, arteriotomic bleeding times, platelet accumulation in vivo, patency, and the amounts of intraluminal red thrombotic material were recorded. The rabbits were divided into two groups. In group A (12 vessels) the vessel interior was flushed with 2 ml of saline or Ringer's lactate solution. Group B (11 vessels) was similar except that the vessels were flushed with 2 ml of heparin, 100 IU/ml, in Ringer's lactate solution. In the control group (A) the bleeding time was 5 +/- 2 min, while in group B bleeding was so profuse that extra sutures had to be used in 6 of the vessels. Although significantly fewer platelets accumulated in heparin-treated animals, the patency frequencies and amounts of thrombotic material observed in both groups were similar. The final volume of thrombus formed is thus not always proportional to the degree of platelet accumulation. Washout of small traumatized arteries with heparin is thus not beneficial. PMID- 2316985 TI - Bone lengthening in the craniofacial skeleton. AB - The process of bone lengthening by cortical fracture and gradual distraction of callus has become well established in the enchondral bones of the extremities. In this study the principles of bone lengthening were applied to the membranous bone of the craniofacial skeleton using the growing dog mandible as a model. Six mongrel dogs five months of age were studied. A unilateral, periosteal-preserving angular corticotomy was performed, and an external minilengthening device was fixed to the mandible perpendicular to the corticotomy. After 10 days of external fixation, the mandible was lengthened 1 mm/day for 20 days and then held in external fixation for 56 days (8 weeks) after which all dogs were killed. Anthropometric measurements and histological analysis of the specimens confirmed that bone lengthening had occurred and that new cortical bone was formed in the expanded areas. PMID- 2316987 TI - Cleft earlobe repair. AB - This is a retrospective study of 9 patients who underwent a total of 11 repairs for cleft earlobe. Two repairs were performed using the simple technique, and 9 were repaired using the L-plasty technique. The mean follow-up was 5.5 months (range, 2-18 months). Both of the simple repairs were judged to have moderate notching along the inferior lobular border, and 1 of the 9 L-plasty repairs was judged to have a slight notching. There were no complications. We believe that the L-plasty technique offers a better cosmetic result in the repair of the cleft earlobe. This technique breaks the vertical component of scar contracture, resulting in a smooth lobular border. In addition, a variation on this technique allows for a simultaneous reduction of the lobule when indicated. PMID- 2316986 TI - Improvement in blood flow and diameter of the postanastomotic rat tail artery by topical application of lidocaine in varying concentrations. AB - Prolonged spasm in small vessels is a major problem after microsurgical procedures. Topical agents applied to resolve these spasms have been the subject of many experimental studies. In this model we studied the effectiveness of various concentrations of lidocaine in resolving microvascular spasms induced by anastomosing the ventral rat tail artery. PMID- 2316988 TI - Injection of illicit drugs into the granulation tissue of chronic ulcers. AB - Chronic skin ulcers are rare among healthy young adults. Local injection of cocaine and heroin has been identified as a cause of chronic skin ulcers in young adults abusing intravenous drugs. These patients use both engorged veins surrounding the ulcers and the granulation tissue itself for the injection of drugs. We believe that chronic skin ulcers in young adults should be a marker for intravenous drug abuse, and should be considered in the differential diagnosis of nonhealing wounds. PMID- 2316989 TI - Nipple centralization for the correction of breast deformity from segmental mastectomy. AB - A breast deformed by lateral tissue deficiency and severe lateral displacement of the nipple, caused by the treatment of an early breast cancer with segmental mastectomy and radiotherapy, was corrected by a modification of techniques used commonly for mastopexy. The nipple and areola were moved medially on a central pedicle to create the illusion that the missing lateral tissues had been restored. Simultaneously, the opposite breast was reduced to improve symmetry. The result was a normalization of breast appearance without the need for distant tissue. It is possible that modifications of this approach could be used to treat similar deformities in other quadrants of the breast as well. PMID- 2316990 TI - Infection following cranial bone grafting--a need for caution? AB - A case of delayed infection following the use of split-cranial bone graft is presented. Trauma and bacterial contamination of the donor area six months before harvest were the likely causes. We advise caution and the use of alternate donor sites in cases where a history of previous contaminating trauma exists, even if the cranial bone is clinically completely healthy. PMID- 2316991 TI - Acute Pseudomonas chondritis as a sequel to ear piercing. AB - A patient is reported who had Pseudomonas chondritis secondary to ear piercing. The cause, pathogenesis, symptoms, and diagnosis of acute chondritis are discussed. Principles of treatment are enumerated. PMID- 2316994 TI - [Minimal lipid anomalies in a group of men with early coronary disease compared to a control group]. AB - A group of 27 men with early coronary disease (mean age: 52 years) with cholesterol levels below 6.45 mmol/l and triglycerides levels below 2.3 mmol/l, who underwent a coronary angiography, is compared with a control group of 18 men (CG) with normal angiography. The only significant differences between the two groups are: a triglycerides levels slightly higher in the CM group (1.55 + 0.4 mmol/l) vs 1.18 +/- 0.37 mmol/l, p 0.001), a HDL-cholesterol level slightly lower in the CM group (1.08 +/- 0.19 mmol/l vs 1.26 +/- 0.21 mmol/l, p 0.01) and an Apo AI/Apo B ratio slightly lower in the CM group (1.02 +/- 0.24 vs 1.18 +/- 0.17, p 0.005). In the CM group, 21 patients in 27 present a lipid abnormality requiring, according to the European consensus recommendations, the prescription of hygieno dietetic measures. In the CM group, 10 patients in 18 present a minimal lipid abnormality, also requiring hygieno-dietetic measures. These results are compared with the recommendations of the European consensus. PMID- 2316993 TI - Syringe aspiration and fat concentration: a simple technique for autologous fat injection. AB - Autologous fat grafting, a technique used earlier this century, has recently been proposed for reconstruction of contour defects, especially of the face. A simple technique is described for harvesting fat, removing serum, blood, and liquid fat, and then injecting the concentrated fat into contour defects. Atraumatic harvesting and fat concentration are the keys to greater fat graft survival. PMID- 2316992 TI - Buried inferiorly based gluteus maximus musculocutaneous flap for reconstruction of large, recurrent ischiopubic pressure sores. AB - The ischium is the most common site for recurrence of pressure sores in the paraplegic population. Successful reconstruction of these wounds depends on the total excision of ulcer, soft tissue debris, bony prominence, and the durability of the soft tissue repair. The V-Y gluteus maximum musculocutaneous flap based on the inferior gluteal vessels can be advanced medially, deepithelialized, and buried to fill large, deep soft tissue ischial wounds. Local rotational flaps close the superficial wound. This buried flap, although not previously described, is useful for the reconstruction of large ischiopubic pressure sores initially or at the time of recurrence. PMID- 2316995 TI - [Arterial injuries caused by the insertion of an intra-aortic counterpulsion balloon]. AB - Insertion of an intra-aortic counterpulsion balloon was necessary following 283 surgical procedures with the heart pump at Hospital Broussais. One instance of vascular trauma at the site of insertion of the balloon was reported in 36 cases (13 p. cent). This was treated according to the severity of the arterial lesion with the following techniques: closure with Goretex venous patch (n = 25), short ilio-femoral by-pass (n = 9) and extra-anatomical femoro-femoral by-pass (n = 2). The overall mortality of the patients who required an intra-aortic balloon was 19 p. cent, including one case of retrograde aortic dissection at the site of insertion of the balloon. The morbidity related to the insertion of the balloon was as follows: one leg amputation, two disabling intermittent claudication episodes. PMID- 2316996 TI - [Natural course of type III traumatic chronic dissection in a patient with Marfan's syndrome]. AB - Description of a traumatic dissection of the descending thoracic aorta, occurring in a female patient with Marfan's syndrome, the chronic course of which over more than three years was complicated by retrograde extension to the ascending thoracic aorta, resulting in death by massive aortic insufficiency and pleuro pericardial effusion. Advantages of clinical and sonocardiographic monitoring of chronic dissections. PMID- 2316998 TI - [Treatment of type A aortic dissection by exclusive gluing. Long-term results apropos of 15 patients]. AB - Between 1984 and 1988, 15 patients with a type A aortic dissection were treated with direct suturing of the entry opening of the dissection and gluing of the dissected aortic layers using the GRF glue (gelatine-resorcine-formaldehyde), without prosthetic replacement. An associated aortic insufficiency, in 10 patients, was treated with valve replacement (5 patients) or plasty (5 patients). Deep hypothermia with circulatory arrest were necessary in 10 patients whose dissection reached the ascending aorta. All patients survived the procedure. These patients are followed from 6 to 44 months. They are all controlled by echo Doppler. In addition, ten had an angiography, 6 a control scan and 5 a NMR. In twelve patients, the ascending aorta as well as the aortic junction are normal. A limited aortic dissection which did not require a secondary procedure, is found in 3 patients. A dissection of the descending aorta is present in 10 patients. Two patients had to be re-operated: one, for a valve replacement, 18 months later; the other, for a myocardiopathy at the terminal stage, 14 months later, requiring an orthotopic transplantation. These results show that gluing of the aorta is an easy and effective treatment in type A aortic dissections. PMID- 2316997 TI - [Auricular flutter disclosing cardiac tumor]. AB - It is unusual that an atrial flutter reveals a tumor of the atrium. Two cases are reported: one occurred in a patient with a myxoma of the left atrium, the other was found in a patient with a non-hodgkinian lymphoma of the right atrium. The diagnosis was made possible by sonocardiography in both cases. The transesophageal view improves the quality of the images. MRI provided further informations regarding the lymphoma. Modern techniques of cardiac imaging permit the early diagnosis and treatment of cardiac tumors which must be investigated in case of apparently isolated atrial arrhythmias. PMID- 2317000 TI - [Value of echocardiography in aged patients with presumed idiopathic auricular fibrillation]. AB - Thirty seven patients (mean age = 80.2 years with extremes from 66 to 98 years), presenting atrial fibrillation (AF), presumably idiopathic (non known heart disease, completely normal cardiac auscultation, good quality chest X-ray and electrocardiogram, no laboratory test anomaly), and paroxystic (n = 7: 19 p. cent) or permanent (n = 30: 81 p. cent), were given an electrocardiogram TM and bidimensional. In only 9 of them (24.3 p. cent), this examination is completely normal. Three other patients (8.1 p. cent) present an isolated dilatation of the left atrium. The 25 remaining patients present various cardiopericardic anomalies: valvular pathologies (n = 2: 59.4 p. cent): mitral (n = 15: 40.5 p. cent) more often than aortic (n = 7: 18.9 p. cent); myocardiopathies (n = 8: 21.6 p. cent), hypertrophic (n = 2), dilated (n = 4) or hypertrophic and dilated (n = 2); moderate pericardial effusion (n = 1: 2.7 p. cent). The mean left and right ventricular diameters, measured in TM mode, are normal as well as the mean contractility indexes (percentage of shortening of the small axis, stroke volume) and the mean filling index (mitral gradient EF) of the LV. Overall, the transverse diameter of the LA is moderately increased (41.9 +/- 9.7 mm); it is not significantly different from the AF, either paroxystic (41.5 +/- 4.9 mm) or permanent (42 +/- 9.93 mm) and whether it is (40.5 +/- 9.9 mm =) or not (42.5 +/- 8.8 mm) complicated by a systemic embolism, especially cerebral. Therefore, the sonocardiogram demonstrates a latent cardiopathy in two-thirds of the patients over 65 presenting a presumably idiopathic AF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2316999 TI - [Auriculoventricular block disclosed in the exercise test]. AB - Sixteen patients, 14 of whom described stress related symptoms, present a severe atrio-ventricular block (A-V B), identified during a stress test while the ECG at rest showed a 1/1 atrioventricular conduction (AV). The electrophysiological study (EPS) creates the A-B Block through atrial stimulation and specifies the location of the A-V B: intra-hissian in 8 patients (7 with small QRS an 1 with widened QRS) and infra-hissian in 8 patients (all with widened QRS). Non-invasive methods constitute the prime approach in the diagnostic work-up of stress symptoms. The ideal treatment consists of a dual-chamber cardiac stimulation. PMID- 2317002 TI - The adaptive significance of Polynesian body form. AB - The Polynesian people who settled a wide area of the tropical Pacific have a large and muscular body phenotype that appears to contradict the classical biological rules of Bergmann and Allen. However, a scrutiny of the conditions actually experienced by these canoe voyagers and small-island dwellers suggests that in reality the oceanic environment is labile and frequently very cold, and from it tribal technology offered little protection. The Polynesian phenotype is considered to be appropriate to, and have undergone selection for, this oceanic environment. PMID- 2317003 TI - Anthropometric measurements of Saudi boys aged 6-14 years. AB - Anthropometric measurements of 1169 Saudi school boys between the ages of 6 and 14 years are reported. The boys were randomly selected from primary schools in the city of Riyadh, Saudi Arabia. Measurements of height, weight, grip strength, chest, triceps and subscapular skinfold thicknesses as well as biacromial, chest, bi-iliac, knee, and elbow breadths were taken. Saudi boys have slightly lower values for body weight and height than American boys (NCHS standards). Values of skinfold measurements increased with age up to age 11 where they plateaued and took then a sharp increase by age 14. Means of triceps and subscapular skinfolds of the Saudi boys are also lower than some standards from U.S.A. throughout age 13. At age 14, however, the Saudi boys have higher means than the U.S.A. boys. PMID- 2317001 TI - Height and mortality in the counties of England and Wales. AB - Average heights of adults and children in the counties of England and Wales were examined using national samples of people born between 1920 and 1970. Although height increased over this 50-year period the differences between counties persisted. Average height in a county is closely related to its pattern of death rates, which were derived from all deaths during 1968-78. Counties with taller populations have lower mortality from chronic bronchitis, rheumatic heart disease, ischaemic heart disease and stroke, and higher mortality from three hormone-related cancers, of the breast, prostate and ovary. The inverse relation of height with bronchitis and cardiovascular disease is further evidence of risk factors acting in early childhood. The positive relation between height and cancers of the breast, ovary and prostate could suggest that promotion of child growth has disadvantages as well as benefits. PMID- 2317004 TI - Sibling similarity in annual growth increments in schoolchildren from a rural community in Oaxaca, Mexico. AB - Sibling similarity in annual growth increments was analysed in schoolchildren, aged 6-13 years, from a Zapotec-speaking, subsistence agricultural community in the Valley of Oaxaca in southern Mexico. Sibling correlations for 44 brother brother, 44 sister-sister, and 110 unlike sex pairs were computed for 17 dimensions holding constant environmental effects, age difference between siblings, and the growth status of each sibling for the dimension. Correlations are negative or close to zero. The lack of similarity between siblings in annual growth increments perhaps reflects age-specific variation in a genotype environment interaction with chronic undernutrition, the important mediating environmental variable. PMID- 2317005 TI - Age of menarche in Bolivian girls of European and Aymara ancestry. AB - Median age of menarche was determined in children of European and Aymara ancestry residing in La Paz, Bolivia (3600 m) and in children of European ancestry residing in Santa Cruz, Bolivia (400 m). Median age of menarche in European and Aymara highland natives was younger than reported by previous researchers, thus broadening the range of variation in age of menarche in high-altitude populations. Comparisons between La Paz and Santa Cruz European children suggested that growth and development at high altitudes results in a delay in median age of menarche of about 0.8 years. PMID- 2317006 TI - On correlations between adjacent velocities and accelerations in longitudinal growth data. AB - Correlations are examined between adjacent velocity and acceleration growth in stature, weight and skinfold thickness in a group of adolescent boys measured approximately quarterly. It is concluded that some substantial component of the variability behaves rather like measurement error, and this is likely to represent negative feedback homeostasis. PMID- 2317007 TI - Isonymy in emigrants from Ferrara in 1981-1988. AB - The distribution of surnames in the emigrants from the population of the town of Ferrara in the period 1981-88 was studied by sex and place of birth, namely Ferrara versus other places. Emigrants born in Ferrara were defined as first time emigrants and those who had previously immigrated to Ferrara were defined second time emigrants. It was found that random isonymy is smaller in second time emigrants. Sex ratio is not different in the two types of emigrants. As indicators of the abundance of surnames in a distribution, the common ecological indexes derived from entropy were used and compared between types of emigrants. It was found that redundancy, as isonymy, is larger in the first time emigrants than in second time emigrants. It was observed that second time emigrants were consistently and significantly older than first time emigrants, and that a considerable fraction of them, (22.4%) returned to their place of birth. A sexual dimorphism in age at emigration was observed in second time emigrants, females emigrating at an older age than males. PMID- 2317009 TI - Prenatal and perinatal antecedents of febrile seizures. AB - We examined prenatal and perinatal characteristics as possible risk factors for febrile seizures in a large pediatric population. Family history was among the few identified factors that made an important contribution to vulnerability to febrile seizures; however, no more than 6% of febrile seizures could be attributed to a characteristic of family history. Maternal illness, smoking history, and a few rare neonatal characteristics were associated with increases in risk. No complication of labor or delivery was an important risk factor for febrile seizures. PMID- 2317008 TI - Dystonia gene in Ashkenazi Jewish population is located on chromosome 9q32-34. AB - Idiopathic torsion dystonia (ITD) is a neurological disorder characterized by sustained muscle contractions that appear as twisting movements of the limbs, trunk, and/or neck, which can progress to abnormal postures. Most familial forms of ITD follow autosomal dominant transmission with reduced penetrance. The frequency of ITD in the Ashkenazi Jewish population is five to ten times greater than that in other groups. Recently, a gene for ITD (DYT1) in a non-Jewish kindred was located on chromosome 9q32-34, with tight linkage to the gene encoding gelsolin (GSN). In the present study linkage analysis using DNA polymorphisms is used to locate a gene responsible for susceptibility to ITD in 12 Ashkenazi Jewish families. This dystonia gene exhibits close linkage with the gene encoding argininosuccinate synthetase (ASS), and appears by multipoint analysis to lie in the q32-34 region of chromosome 9, a region that also contains the loci for gelsolin and dopamine-beta-hydroxylase. The same gene may be responsible for ITD both in the non-Jewish kindred mentioned above and in the Ashkenazi Jewish families presented here. However, because there is substantial difference between the penetrance of the dominant allele in these two groups, two different mutations may be operating to produce susceptibility to this disease in the two groups. PMID- 2317010 TI - Immunological studies in tropical spastic paraparesis. AB - Tropical spastic paraparesis (TSP) and other chronic-progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T-lymphotropic virus type I (HTLV-I). However, little is known about the cellular immune function in TSP. In the present study, activated T lymphocytes were found in the peripheral blood of patients with TSP. Specifically, there were increased numbers of large CD3+ cells that also expressed HLA-DR and interleukin-2-receptor molecules. A significantly elevated spontaneous lymphoproliferative response was demonstrated in all patients tested. Generation of measles virus-specific cytotoxic T-cell response was reduced in 4 of 4 patients. This was similar to previous findings in patients with multiple sclerosis. However, unlike multiple sclerosis, reduced generation of cytotoxic T cell response to influenza and mumps viruses was observed in 2 of 4 patients. These observations confirm further the strong association between TSP and an HTLV I-like virus and suggest that the observed abnormalities of the cellular immune response in TSP are related to infection of lymphocytes by the retrovirus. PMID- 2317011 TI - Regional cerebral blood flow during focal seizures of temporal and frontocentral onset. AB - Ictal single photon emission computed tomography recordings were performed in 9 patients in the course of 11 seizures. Injections of radionuclide were made an average of 72 seconds after the onset of the seizure as indicated by electroencephalography. All patients also underwent interictal recordings. In 6 patients, the localization of the electroencephalographic focus and the morphological lesions corresponded with the ictal hyperperfusion. This could be seen in single photon emission computed tomography. Seizures triggered by hyperventilation, and seizures of patients with anatomical brain lesions (e.g., cysts, surgical defects, and recent injections of technetium-hexamethylene propylene-amine-oxime) showed an absent or noncorresponding localization of the ictal recording. The ictal and interictal recording seems suitable as a confirmatory noninvasive method for the localization of the epileptogenic focus, particularly in the preoperative evaluation of epilepsy. PMID- 2317012 TI - Hyperfractionated radiotherapy for children with brainstem gliomas: a pilot study using 7,200 cGy. AB - Brainstem gliomas, constituting approximately 10% of all childhood central nervous system tumors, remain the most resistant of all brain tumors to therapy. A subgroup of high-risk patients with tumors that diffusely involve the brainstem or that microscopically demonstrate foci of anaplasia on biopsy specimens rarely survive after treatment. Conventional doses of radiotherapy result in temporary clinical improvement in the majority of these high-risk patients; however, few if any remain alive 18 months after treatment. Hyperfractionated radiotherapy, with delivery of larger numbers of smaller fractions of radiotherapy, is a possible way to increase tumor control without increasing neurological toxicity. In 1985, a multiinstitutional phase I/phase II trial, using 100 cGy of radiation therapy twice daily to a total dose of 7,200 cGy, was undertaken for patients with high risk brainstem gliomas. At the time of writing, 24 (69%) had developed progressive disease and 11 remained in continuous progression-free remission. Actuarial progression-free survival at 20 months is approximately 30%. Twenty three of 31 evaluable patients had an objective radiographic response to therapy. In comparison to both historical control patients and patients treated in a previous trial using 6,480 cGy of hyperfractionated radiation therapy, there was a statistically significant improvement in progression-free survival rate for patients treated with 7,200 cGy of hyperfractionated radiation therapy (p less than 0.01). To date no patient has died as a result of treatment. Six patients developed transient neurological deterioration or cystic intralesional changes, as demonstrated on magnetic resonance imaging, within 6 weeks of the completion of radiotherapy. Postmortem examination performed in 7 patients did not disclose significant radiation necrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317013 TI - Increased thymocyte differentiation in myasthenia gravis: a dual-color immunofluorescence phenotypic analysis. AB - Thymocytes express multiple, different surface antigens according to their stage of maturation. Surface differentiation antigens have been studied with the technique of simultaneous dual-color, direct immunofluorescence in the thymuses of 20 patients with myasthenia gravis (MG) and 10 control subjects with cardiac diseases. Fluorescein isothiocyanate-conjugated and phycoerythrin-conjugated monoclonal antibodies were used to stain thymic cell suspensions. A significant decrease in the percentage of immature and common thymocyte phenotypes (CD1+,3+ and CD4+,8+) and a significant increase in the percentage of mature thymocyte phenotypes (CD1-,3+; CD4+,8-; and CD4-,8+) and of B cells (CD20+) were found in MG thymuses compared with controls. These data, indicating an increased availability of mature, fully immunocompetent T and B cells, indirectly suggest the occurrence of an active immune response in MG thymus. PMID- 2317014 TI - Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis. AB - 4-Aminopyridine (4-AP), a potassium channel blocker, restores conduction in blocked, demyelinated animal nerve. Its administration to multiple sclerosis (MS) patients produces transient neurological improvements. Vision improves after either oral or intravenous administration, whereas motor function improvement has been reported only with the latter. To assess further its potential as a practical symptomatic treatment, we studied the efficacy of single, oral doses of 4-AP on both visual and motor signs in MS. Twenty temperature-sensitive male MS patients were given either 10 to 25 mg of 4-AP or identically appearing lactose placebo capsules. Static quantitative perimetry, critical flicker-fusion, visual acuity, visual evoked potentials, and videotaped neurological examinations were monitored. All of 15 MS patients given 4-AP mildly to markedly improved. Motor functions (power, coordination, gait) improved in 9 of 13 involved, vision in 11 of 13, and oculomotor functions in 1 of 2. Improvements developed gradually at doses as low as 10 mg, usually beginning within 60 minutes after drug administration, and reversed gradually over 4 to 7 hours. No serious adverse effects occurred. No significant changes were observed in 5 MS patients given placebo. We conclude that orally administered 4-AP produces clinically important improvements in multiple, chronic deficits in MS. Further studies are warranted to assess efficacy and safety of prolonged administration. PMID- 2317015 TI - A disorder of axonal development, necrotizing myopathy, cardiomyopathy, and cataracts: a new familial disease. AB - We report severe congenital encephalopathy and profound hypotonia associated with necrotizing myopathy, cardiomyopathy, and cataracts in 3 infants, including 2 sisters. Brain scans suggested agenesis of the corpus callosum. Neuropathological findings consisted of severe atrophy of the corpus callosum (not the usual agenesis with longitudinal callosal bundles), atrophy of the white matter, and absence of pyramidal tracts in the medulla. Multiple axonal swellings were present in the white matter and in Purkinje cells. Except for the corpus subthalamicum, gray matter structures were preserved. These findings are considered to be the expression of a primary disorder of axonal development leading to a reduction in interneuronal synaptic contacts. It is suggested that the anomaly may be due to an extension of the normal phenomenon of axonal elimination, related to a primary defect of the axonal cytoskeleton. The concept of a primary axonal disorder may also apply to other, mostly familial, conditions with progressive atrophy of the cerebral white matter and corpus callosum. PMID- 2317016 TI - Neurosyphilis in the patient infected with human immunodeficiency virus. PMID- 2317018 TI - Celebrating OR nurse day. PMID- 2317017 TI - Opercular sign: significance beyond cerebral dysgenesis. PMID- 2317019 TI - Reader questions wrapping endotracheal tubes. PMID- 2317020 TI - Integrated systems; system growth; modems; vendors; computer literacy. PMID- 2317021 TI - Single lung transplantation. New treatment for end-stage pulmonary disease. AB - Single lung transplants have become a reality. In the 1990s, the development of transplant teams will be an issue for OR nursing. Operating room nurses must be prepared to provide preoperative, intraoperative, and postoperative nursing care for transplant patients. Although single lung transplant procedures still are in their infancy, the procedures continue to be refined through research and clinical evaluation. Single lung transplants are the key to the future for treating end-stage pulmonary disease. PMID- 2317022 TI - Left ventricular rupture. A collaborative approach to emergency management. PMID- 2317023 TI - Dental implants. Permanent replacement for lost teeth. AB - Implant complications are rare, but they can include nerve injury, bone loss, infection, injury to adjacent teeth and their supporting structures, premature loss of implants or the prosthesis fitted on the implant, bone fracture, and oroantral (ie, mouth, maxillary sinus) and oronasal (ie, mouth, nose) fistulae. Oral implants represent a new technological possibility. Whether it is used to replace a single tooth, several missing teeth, or an entire dentition, dental implants restore the feeling of having one's own natural teeth. This can improve the patient's physical and psychological health. PMID- 2317024 TI - Facial dermabrasion. Modern techniques and protocols. PMID- 2317025 TI - Patient advocacy. The essence of perioperative nursing in ambulatory surgery. PMID- 2317026 TI - The autonomous endoscopy unit. Designing it for maximum efficiency. PMID- 2317027 TI - Intraoperative endoscopy of the small bowel. Treatment for occult hemorrhage. PMID- 2317028 TI - Failure. Making it a positive experience. AB - It is naive to think that all failures can be viewed as positive. Failure hurts. It can create the lowest of the lows and anxieties that you did not know existed. It is not fatal, however, nor is it contagious. Most of all, it is not permanent. Failure is an event. It can be judged by how we view it and how others tell us to view it. We do not have to accept others' opinions about the event. We do have to decide how we will interpret it and manage it. It is the way we cope with failure that shapes us, not the failure itself. The real strength of character comes from knowing that we will survive, that survival will ensure a better life, and that we can learn to manage both our successes and failures. PMID- 2317030 TI - Choosing management. It is not for everyone. PMID- 2317029 TI - Applying Parse's theory to perioperative nursing. A nontraditional approach. PMID- 2317031 TI - 12-hour shifts. A scheduling alternative for ORs. PMID- 2317032 TI - Made-to-order suture packs. Increasing OR efficiency. PMID- 2317033 TI - Recommended practices. Surgical attire. AORN Technical Practices Coordinating Committee. PMID- 2317034 TI - Recommended practices. Sponge, sharp, and instrument counts. AORN Technical Practices Coordinating Committee. PMID- 2317035 TI - Incident reports may or may not be privileged information. AB - Whether incident reports are discoverable depends on the purpose of the reports and the laws of the state where the reports are filed. Subtle differences in state laws and/or how reports are used can make major differences in the determination. These differences are for hospital attorneys to study and consider. In addition to anticipating litigation, hospitals may use incident reports to promote hospital safety and prevent general losses. The hospital, not the nurse, decides if incident reports will be used in a manner more likely to protect the reports from discovery or if protection from discovery is of less concern (either because of state law or corporate philosophy). These decisions will determine how the forms are printed, when reports should be filed, what information is required, how many copies are made, and to whom the copies are distributed. Perioperative nurses need only follow the facility's policy and procedure for completing and filing incident reports. If the hospital attempts to protect reports from discovery, it is especially important that the procedure be followed precisely. PMID- 2317036 TI - Admission/discharge unit alleviates overcrowding. PMID- 2317037 TI - Sharing the perioperative role with nursing colleagues. PMID- 2317038 TI - Detection of ruminal bacteria that degrade toxic dihydroxypyridine compounds produced from mimosine. AB - Leucaena leucocephala, a tropical leguminous shrub, contains a toxic amino acid, mimosine. Successful utilization of leucaena as a ruminant forage depends on colonization of the rumen by bacteria that degrade dihydroxypyridines (DHP), which are toxic intermediates in the metabolism of mimosine. Populations in the rumina of animals in some parts of the world, however, do not include bacteria that are able to carry out this degradation. We thus describe tests for the presence of DHP degraders in ruminal populations that are based on degradation (loss) of DHP compounds from culture media. Results obtained with the tests indicate that DHP degraders were not part of microbial populations in the rumina of cattle, sheep, and goats in Iowa, while most rumen samples examined from animals from the Virgin Islands and Haiti contained DHP degraders. These results confirm and extend the findings of others about geographic limits to the distribution of these important ruminal bacteria. PMID- 2317039 TI - Purification and properties of an acetoacetyl coenzyme A-reacting phosphotransbutyrylase from Clostridium beijerinckii ("Clostridium butylicum") NRRL B593. AB - During the study of acetoacetyl coenzyme A (CoA)-reacting enzymes of Clostridium beijerinckii NRRL B593, a phosphate-dependent acetoacetyl-CoA-utilizing activity was detected in protein fractions devoid of thiolase and phosphotransacetylase. Further purification of this acetoacetyl-CoA-utilizing activity yielded an enzyme which may be designated as phosphotransbutyrylase (PTB; phosphate butyryltransferase [EC 2.3.1.19]). PTB from C. beijerinckii NRRL B593 was purified 160-fold with a yield of 14% and, with the best fractions, purified 190 fold to near homogeneity. It showed a native Mr of 205,000 and a subunit Mr of 33,000. PTB activity was sensitive to pH changes within the physiological range of 6 to 8. PTB exhibited a broad substrate specificity. The Km values at pH 7.5 for butyryl-CoA, acetoacetyl-CoA, and acetyl-CoA were 0.04, 1.10, and 3.33 mM, respectively. The Vmax values with butyryl-CoA and acetoacetyl-CoA were comparable, but the Vmax/Km was higher for butyryl-CoA than for acetoacetyl-CoA. An apparent Km of 6.5 mM for phosphate was obtained with butyryl-CoA as the cosubstrate, whereas it was 12.9 mM with acetoacetyl-CoA as the cosubstrate. It remains to be established whether the putative compound acetoacetyl phosphate is produced in the PTB-catalyzed reaction with acetoacetyl-CoA. PMID- 2317040 TI - Deposition of manganese in a drinking water distribution system. AB - The deposition of manganese in a water distribution system with manganese-related "dirty water" problems was studied over a 1-year period. Four monitoring laboratories with Robbins biofilm sampling devices fitted to the water mains were used to correlate the relationship among manganese deposition, the level of manganese in the water, and the chlorination conditions. Manganese deposition occurred by both chemical and microbial processes. Chemical deposition occurred when Mn(II) not removed during water treatment penetrated the filters and entered the distribution system, where it was oxidized by chlorine and chlorine dioxide used for disinfection. Microbial deposition occurred in areas with insufficient chlorination to control the growth of manganese-depositing biofilm. At 0.05 mg of Mn(II) per liter, the chemical deposition rate was much greater than microbial deposition. Significant deposition occurred at 0.03 mg of manganese per liter, and dirty water complaints were not eliminated until manganese levels were continuously less than 0.02 mg/liter and chlorination levels were greater than 0.2 mg/liter. A guideline level of 0.01 mg of manganese per liter is recommended. PMID- 2317041 TI - Stereoselective fungal metabolism of methylated anthracenes. AB - The metabolism of 9-methylanthracene (9-MA), 9-hydroxymethylanthracene (9-OHMA), and 9,10-dimethylanthracene (9,10-DMA) by the fungus Cunninghamella elegans ATCC 36112 is described. The metabolites were isolated by high-performance liquid chromatography and characterized by UV-visible, mass, and 1H nuclear magnetic resonance spectral techniques. The compounds 9-MA and 9,10-DMA were metabolized by two pathways, one involving initial hydroxylation of the methyl group(s) and the other involving epoxidation of the 1,2- and 3,4- aromatic double bond positions, followed by enzymatic hydration to form hydroxymethyl trans dihydrodiols. For 9-MA metabolism, the major metabolites identified were trans 1,2-dihydro-1,2-dihydroxy and trans-3,4-dihydro-3,4-dihydroxy derivatives of 9-MA and 9-OHMA. 9-OHMA was also metabolized to trans-1,2- and 3,4-dihydrodiol derivatives. The absolute configuration and optical purity were determined for each of the trans-dihydrodiols formed by fungal metabolism and compared with previously published circular dichroism spectral data obtained from rat liver microsomal metabolism of 9-MA, 9-OHMA, and 9,10-DMA. Circular dichroism spectral analysis revealed that the major enantiomer for each dihydrodiol was predominantly in the S,S configuration, in contrast to the predominantly R,R configuration of the trans-dihydrodiol formed by mammalian enzyme systems. These results indicate that C. elegans metabolizes methylated anthracenes in a highly stereoselective manner that is different from that reported for rat liver microsomes. PMID- 2317042 TI - Bioconversion of possible T-2 toxin precursors by a mutant strain of Fusarium sporotrichioides NRRL 3299. AB - Liquid cultures of a mutant strain of Fusarium sporotrichioides NRRL 3299 that accumulates trichodiene rather than T-2 toxin converted tricho-9-ene-2 alpha,3 alpha,11 alpha-triol, trichotriol (tricho-10-ene-2 alpha,3 alpha,9 alpha-triol), tricho-10-ene-2 alpha,3 alpha,9 beta-triol, 3 alpha-hydroxytrichothecene, and 3 alpha-acetoxytrichothecene to T-2 toxin. Other possible oxygenated precursors of T-2 toxin, including trichodiol (tricho-10-ene-2 alpha,9 alpha-diol), trichothecene, 4 alpha-hydroxytrichothecene, and 15-hydroxytrichothecene, were not metabolized. The results indicate that in the biosynthesis of T-2 toxin by F. sporotrichioides, (i) oxygenation at C-3 occurs prior to the second cyclization, (ii) this second cyclization involves two steps that may be nonenzymatic, and (iii) oxidation at C-3 precedes that at C-4 or C-15. PMID- 2317044 TI - DNA hybridization to compare species compositions of natural bacterioplankton assemblages. AB - Little is known about the species composition and variability of natural bacterial communities, mostly because conventional identification requires pure cultures, but less than 1% of active natural bacteria are cultivable. This problem was circumvented by comparing species compositions via hybridization of total DNA of natural bacterioplankton communities for the estimation of the fraction of DNA in common between two samples (similarity). DNA probes that were labeled with 35S by nick translation were hybridized to filter-bound DNA in a reciprocal fashion; similarities (in percent) were calculated by normalizing the values to self-hybridizations. In tests with DNA mixtures of pure cultures, the experimentally observed similarities agreed with expectations. However, reciprocal similarities (probe and target reversed) were often asymmetric, unlike those of DNA from single strains. This was due to the relative complexity and G + C content of DNA, which provided a means to interpret the asymmetry that was occasionally observed in natural samples. Natural bacteria were collected by filtration from Long Island Sound (LIS), N.Y., the Caribbean and Sargasso seas, and a coral reef lagoon near Bermuda. The samples showed similarities of less than 10 to 95%. The LIS and Sargasso and Caribbean sea samples were 20 to 50% similar to each other. The coral reef sample was less than 10% similar to the others, indicating its unique composition. Seasonality was also observed; an LIS sample obtained in the autumn was 40% similar to two LIS samples obtained in the summer; these latter two samples were 95% similar. We concluded that total DNA hybridization is a rapid, simple, and unbiased method for investigating the variation of bacterioplankton species composition over time and space, avoiding the need of culturing. PMID- 2317043 TI - Assay for the enzymatic conversion of indoleacetic acid to 3-methylindole in a ruminal Lactobacillus species. AB - An assay to measure the rate of enzymatic formation of 3-methylindole (3MI) from indoleacetic acid (IAA) in Lactobacillus sp. strain 11201 was developed. The reaction mixture contained 50 micrograms of microbial protein per ml (range, 25 to 100 mg/ml), essential low-molecular-weight reaction ingredients, and radiolabeled IAA as substrate (range, 0 to 2 mM IAA). The reaction was anaerobic for 25 min at 39 degrees C. The apparent Michaelis-Menten constants were: Km, 0.14 mM IAA; and Vmax, 64 nmol 3MI.mg-1.min-1. The inhibitors avidin, aminopterin, and EDTA had no effect on the 3MI-forming enzyme. Dithionite stimulated the 3MI-forming enzyme. The product of the reaction, 3MI, acted as a noncompetitive inhibitor of the enzyme. Enzyme activity was associated with the cell wall fraction after sonication; treatment with the French press; or treatment with detergents, proteolytic enzymes, and EDTA. PMID- 2317045 TI - Radioimmunoassay of nivalenol in barley. AB - Antibodies against nivalenol (NIV) tetraacetate (Tetra-Ac-NIV) were prepared by immunizing rabbits with a hemisuccinate derivative of 8-hydroxy-3,4,7,15 tetraacetyl-12, 13-epoxytrichothece-9-en conjugated to bovine serum albumin. A radioimmunoassay system with one of these sera was developed to measure NIV contamination in barley. The detection limit for Tetra-Ac-NIV was about 0.5 ng/ml. The relative cross-reactivities of the antiserum with Tetra-Ac-NIV, acetyl T-2 toxin, and scirpenol triacetate, which were determined by the competitive radioimmunoassay, were 1, 0.78, and 0.56, respectively. Other derivatives showed no cross-reactivity. For the determination of NIV in a barley sample, NIV was extracted from the sample with acetonitrile-water (7:3), defatted with hexane, and then acetylated with acetic anhydride to form Tetra-Ac-NIV. The reaction mixture was loaded onto a C18 cartridge to remove excess reagents and impurities. Tetra-Ac-NIV was eluted from the cartridge with 50% methanol in water, and the eluate was subjected to radioimmunoassay. Analysis of six naturally contaminated barley samples for NIV revealed that radioimmunoassay results agreed well with gas chromatographic analyses. PMID- 2317046 TI - High diversity in DNA of soil bacteria. AB - Soil bacterium DNA was isolated by minor modifications of previously described methods. After purification on hydroxyapatite and precipitation with cetylpyridinium bromide, the DNA was sheared in a French press to give fragments with an average molecular mass of 420,000 daltons. After repeated hydroxyapatite purification and precipitation with cetylpyridinium bromide, high-pressure liquid chromatography analysis showed the presence of 2.1% RNA or less, whereas 5 methylcytosine made up 2.9% of the total deoxycytidine content. No other unusual bases could be detected. The hyperchromicity was 31 to 36%, and the melting curve in 1 X SSC (0.15 M NaCl plus 0.015 M sodium citrate) corresponded to 58.3 mol% G+C. High-pressure liquid chromatography analysis of two DNA samples gave 58.6 and 60.8 mol% G+C. The heterogeneity of the DNA was determined by reassociation of single-stranded DNA, measured spectrophotometrically. Owing to the high complexity of the DNA, the reassociation had to be carried out in 6 X SSC with 30% dimethyl sulfoxide added. Cuvettes with a 1-mm light path were used, and the A275 was read. DNA concentrations as high as 950 micrograms ml-1 could be used, and the reassociation rate of Escherichia coli DNA was increased about 4.3-fold compared with standard conditions. C0t1/2 values were determined relative to that for E. coli DNA, whereas calf thymus DNA was reassociated for comparison. Our results show that the major part of DNA isolated from the bacterial fraction of soil is very heterogeneous, with a C0t1/2 about 4,600, corresponding to about 4,000 completely different genomes of standard soil bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317047 TI - Problems associated with identification of Legionella species from the environment and isolation of six possible new species. AB - Following investigation of an outbreak of legionellosis in South Australia, numerous Legionella-like organisms were isolated from water samples. Because of the limited number of commercially available direct fluorescent-antibody reagents and the cross-reactions found with some reagents, non-pneumophila legionellae proved to be difficult to identify and these isolates were stored at -70 degrees C for later study. Latex agglutination reagents for Legionella pneumophila and Legionella anisa developed by the Institute of Medical and Veterinary Science, Adelaide, Australia, were found to be useful as rapid screening aids. Autofluorescence was useful for placing isolates into broad groups. Cellular fatty acid analysis, ubiquinone analysis, and DNA hybridization techniques were necessary to provide definitive identification. The species which were isolated most frequently were L. pneumophila, followed by L. anisa, Legionella jamestowniensis, Legionella quinlivanii, Legionella rubrilucens, Legionella spiritensis, and a single isolate each of Legionella erythra, Legionella jordanis, Legionella birminghamensis, and Legionella cincinnatiensis. In addition, 10 isolates were found by DNA hybridization studies to be unrelated to any of the 26 currently known species, representing what we believe to be 6 possible new species. PMID- 2317049 TI - The power of the written word. PMID- 2317048 TI - Enzymatic profiles of 11 barophilic bacteria under in situ conditions: evidence for pressure modulation of phenotype. AB - Barophilic bacteria are microorganisms that grow preferentially (facultative barophiles) or exclusively (obligate barophiles) under elevated hydrostatic pressure. Barophilic bacteria have been isolated from a variety of deep-sea environments. Attempts to characterize these organisms have been hampered by a lack of appropriate methodologies. A colorimetric method for the detection of 19 constitutively expressed enzymes under in situ conditions of pressure and temperature has been devised, using a simple modification of the commercially available API ZYME enzyme assay kit. By using this method, enzyme profiles of 11 barophilic isolates, including an obligate barophile, were determined. Nine of the 10 facultatively barophilic isolates examined exhibited a change of phenotype in at least one enzyme reaction when tested at 1 atm (1 atm = 101.29 kPa), compared with results obtained under in situ pressure. The assay is simple and rapid and allows for direct determination of enzyme activity under conditions of high pressure and low temperature. PMID- 2317050 TI - Research utilizaton: an evaluation and critique of research related to oral temperature measurement. AB - The problem addressed was whether a research-based protocol on oral temperature measurement could be developed and used in the practice setting. The first phase of the study proposed to (a) identify research articles related to the subject; (b) evaluate the quality of the research; (c) assess the adequacy of the research base; and (d) select areas for future study. The results indicated that further clinically-based studies are needed before a protocol can be designed and tested in clinical practice. PMID- 2317051 TI - Strategies for setting and implementing the National Center for Nursing Research priorities. AB - This paper describes the development of the National Nursing Research Agenda (NNRA) of The National Center for Nursing Research (NCNR), a concentrated and long-range effort to set priorities for nursing research. The NNRA process, the contextual characteristics under which the NNRA is carried out, and the strategies for setting and implementing the priorities are discussed. PMID- 2317052 TI - The relationship of age, gender, and exercise practices to measures of health, life-style, and self-esteem. AB - A study of 478 adults from a rural-urban region was conducted to determine differences in health and life-style measures based on age, gender, and exercise involvement that would provide data to incorporate in healthy-living programs. Pender's Health Promotion Model provided the framework for the study. Significant results related to age, gender, exercise, and initiation and maintenance of health-promoting practices were found. PMID- 2317053 TI - Care of HIV-infected patients: nurses' concerns, opinions, and precautions. AB - The purpose of this study was to describe nurses' concerns, opinions, and precautions related to nursing patients infected with the human immunodeficiency virus (HIV). Of special interest was a comparison of responses by nurses who reported exposure to the HIV through broken skin or mucous membranes with the responses of nurses who reported no such exposure. The sample included all staff nurses employed in either the ambulatory/home health care unit or in one of seven inpatient critical care units of a large urban medical center. Of the 323 respondents, 64 (20%) reported HIV exposure, 77 (24%) reported no exposure, and 180 (56%) reported not knowing if they had been exposed. A 15-item Likert-type scale was used. More HIV-exposed nurses than non-exposed nurses reported: (a) worrying about becoming HIV-infected; (b) considering a change of specialty or profession because of the acquired immunodeficiency syndrome (AIDS) risk; and (c) favoring selected HIV-related policies. Of the total sample, nearly all subjects agreed that staff nurses should be involved in developing HIV-related policies affecting nurses; and over one-half said that, if the agency gave them the option, they would refuse assignment to HIV-infected patients. Nearly 30% said that they had considered changing their profession because of the AIDS risk. Some implications are that nursing administrators should involve well-informed staff nurses in formulating HIV-related policies that affect nurses. The HIV-exposed nurses may need support in dealing with their concerns resulting from HIV exposure, and they may need more information about HIV-infection control and seroconversion rates of HIV-exposed nurses. PMID- 2317054 TI - Nurses' responses to separation from their secondborn infants. PMID- 2317055 TI - Measurement of psychophysiologic response variables in chronic bronchitis and emphysema. PMID- 2317056 TI - 'I just pretend it's completely normal': strategies for surviving data collection when researching menarche. PMID- 2317057 TI - Maternal position, labor, and comfort. AB - The purpose of this study was to determine if women who assumed upright positions during the phase of maximum slope would have a shorter phase of maximum slope in their labor and experience more comfort than women who assumed recumbent positions. Forty laboring women were randomly assigned to either an upright or recumbent position group. Subjects assumed the positions of their assigned group during the phase of maximum slope in their labor (cervical dilatation from 4 cm to 9 cm). Every hour during the phase of maximum slope, each subject was examined vaginally to determine her cervical dilatation and assessed for her level of comfort using the Maternal Comfort Assessment Tool. Women in the upright position group had a significantly shorter phase of maximum slope in labor, but did not significantly differ in comfort level from women in the recumbent group. Newborn Apgar scores were not significantly different between the two groups. Nurses need to be aware that the upright labor positions have the distinct advantages of facilitating efficient uterine contractions and reducing the duration of the phase of maximum slope in labor, with no increase in the discomfort experienced or adverse effect on newborn well-being. PMID- 2317059 TI - Estimation of lung volume in infants by echo planar imaging and total body plethysmography. AB - Echo planar imaging (an extremely fast method of magnetic resonance imaging) was used to measure lung volume in a group of nine infants, all of whom had had respiratory problems. The mean echo planar imaging estimate of total lung volume was 44 +/- 9 ml/kg. In each case the right lung was larger than the left (ratio 52.8:47.2%). The mean thoracic gas volume was 36 +/- 8 ml/kg. The entire sequence of images of the thorax (about 400) takes five minutes to complete, infants require no sedation, and there are no side effects. PMID- 2317058 TI - Survey of asthma deaths in the Northern region, 1970-85. AB - Thirty five asthma deaths in children aged 1 to 16 years were investigated in detail. Twenty four of these children had previously been under hospital consultant care and there were seven inpatient deaths. Twenty nine cases (83%) had a history of severe asthma, 17 of whom had previously experienced a life threatening attack. The fatal outcome, however, could not have been predicted in six children (17%) with preceding mild asthma. Potentially preventable factors in management were found in 28 cases (80%). While 18 (51%) had been chronically undertreated, the major factor in 20 deaths (57%) was suboptimal management of the final attack owing to delay in seeking medical attention, inadequate medical response, or both. Only two children had received systemic corticosteroid in appropriate amounts during the final illness. If mortality is to be reduced, families of asthmatic children must be educated to recognise severe symptoms and be given an appropriate 'crisis plan'. Hospitals should permit free access and have a clear protocol for the management of children with severe asthmatic attacks. PMID- 2317060 TI - Airway function in infants with vascular rings: preoperative and postoperative assessment. AB - Aortic arch anomalies in infancy often cause intrathoracic airway obstruction. Airway function was assessed as part of the diagnostic evaluation in six symptomatic infants both by plethysmography and using a chest compression technique to obtain partial flow-volume loops. Two infants had normal intrathoracic airway function and their symptoms were unrelated to aortic arch abnormalities. The remaining four had complete vascular rings (three double aortic arch, one pulmonary sling) and had increased expiratory airway resistance (Raw) (mean Raw = 700% predicted) and greatly decreased maximum flow rates at functional residual capacity (VmaxFRC; mean VmaxFRC = 34% predicted) with gross shape abnormalities of the flow-volume loop. Postoperatively airway function was substantially improved (mean Raw = 175% predicted, VmaxFRC = 79% predicted) but some abnormality of flow-volume loop shape remained, suggesting that tracheal dynamics were not completely normal in the early postoperative period. PMID- 2317061 TI - Bacterial reservoirs in cystic fibrosis. AB - To establish whether colonisation of the upper respiratory tract or bacterial contamination of inhaler devices or solutions predisposes to colonisation of the lower respiratory tract in patients with cystic fibrosis, bacterial isolates from groups of children who were positive (n = 13) or negative (n = 18) for Pseudomonas aeruginosa were studied. Cultures of swabs from inhaler devices, toothbrushes, and upper airways were compared with cough swabs or sputum cultures. No pathogens were obtained from inhaler equipment administering unit dose medications. Upper airway carriage of Staphylococcus aureus and Haemophilus influenzae was identified in both groups but correlated poorly with sputum isolates. P. aeruginosa was found only in the upper respiratory tract of children with established colonisation of the lower airways. No P aeruginosa isolates were obtained from the upper airways of the group with negative sputum, including one patient who became colonised by P aeruginosa during the study. Our results did not support the suggestion that colonisation of the upper respiratory tract by P aeruginosa predisposes to colonisation of the lower airways. Failure to isolate pathogenic organisms consistently from the upper airways in patients with positive sputum argues against a local epithelial factor predisposing to bacterial colonisation. PMID- 2317062 TI - Ontogeny of pancreatic exocrine function. AB - Exocrine pancreatic proteolytic activity, determined by serial measurement of faecal chymotrypsin concentration, was investigated in 21 preterm infants (23-32 weeks' gestation) during the first 28 days of life. The overall chymotrypsin concentration range was similar to that already described in term infants showing that pancreatic chymotrypsin secretion is equally well developed at birth in the preterm infant. A chymotrypsin concentration peak, seen in term infants at 4 days, did not occur in this study until day 8, suggesting a slower initiation of pancreatic exocrine function in the preterm infant. Median faecal chymotrypsin concentrations, calculated for each baby using data from stools passed between day 2 and day 12 of life, were significantly lower in infants who were small for gestational age when compared with those who were an appropriate size for gestational age. The lower chymotrypsin concentration in infants who were small for gestational age suggests a deleterious effect of intrauterine growth retardation on pancreatic exocrine function which may be a factor in limiting postnatal catch up growth. PMID- 2317063 TI - Submucous cleft palate in the differential diagnosis of feeding difficulties. AB - Submucous cleft palate is a missed or forgotten diagnosis. We reviewed 81 patients with submucous cleft palate seen over a 15 year period; 26 of these patients were interviewed. The patients were divided into three main groups according to the referral pattern. Children under 2.5 years were referred by a paediatrician for feeding problems; children aged 2.5-10 were referred mainly by speech therapists; and those over 10 had a varied pattern of referral. Thirty nine of the 81 had problems with feeding, but of the 26 interviewed, 22 had feeding problems. Not all patients with a submucous cleft palate are symptomatic and require active treatment, but children with this condition have the same high incidence of middle ear disease as those with overt cleft palate. We suggest that the diagnosis of submucous cleft palate be included in the differential diagnosis of feeding difficulties, with early referral to a specialist cleft palate team. PMID- 2317064 TI - Factors influencing the presence of faecal lactobacilli in early infancy. AB - The faecal flora of 46 preterm infants and 52 born at full term was studied at 10 days of age; 46 born at full term and 37 preterm infants were also studied at 30 days. Viable counts of coliforms, lactobacilli, and bifidobacteria were made; gas liquid chromatography was used to identify the anaerobes. Lactobacilli, but not bifidobacteria, were found in high counts in the stools of most of the infants born at full term by 30 days of age. The mode of delivery, but not the method of feeding, had a significant influence on early colonisation. A selective deficiency of lactobacilli compared with coliform organisms was found in preterm infants. Previous treatment with antibiotics and being nursed in an incubator were also significantly associated with a lower rate of early colonisation with lactobacilli. Our findings indicate that lactobacilli may be an important part of the normal stool flora in early infancy, and that modern methods of neonatal care are associated with delayed or deficient colonisation. PMID- 2317065 TI - Helicobacter pylori in Gambian children with chronic diarrhoea and malnutrition. AB - Infection with Helicobacter pylori (formerly Campylobacter pylori) was studied by measuring antibody titres to H pylori in Gambian children. Serological evidence of infection was found in 12 of 82 (15%) infants aged less than 20 months; this increased to 62 of 135 (46%) in those aged 40-60 months. Positive serology was found in 41 of 77 (53%) infants with chronic diarrhoea and malnutrition (mean age 19 months, range 5-36) compared with 18 of 70 (26%) of age matched healthy controls and nearly a quarter (12/49, 24%) of age matched undernourished (marasmic) subjects. These data show that infection with H pylori is common in the Gambia and that in infancy this infection is associated with chronic diarrhoea and malnutrition. PMID- 2317066 TI - Understanding non-attendance in outpatient paediatric clinics. AB - Outpatient clinic appointments are often not kept. There has been little study of the reasons for this, but failure to attend may affect future health. Our study was based on the children's outpatient department of a large inner city district general hospital. The parents of 34 children who had failed to keep appointments and of 12 who did attend were interviewed in depth and the appointment systems of the hospital and of a nearby regional referral centre for children were reviewed. At the district general hospital 23% of first appointments and 35% of subsequent appointments were not kept. We found that parents usually made a conscious decision about attending, balancing the perceived advantages and disadvantages of doing so. Their assessment of the severity of the child's illness was crucial in this. Twenty one of the 34 children who had not attended were assessed at the time of interview as still needing to attend. Of these, 16 subsequently kept an appointment and 11 underwent further investigation or treatment. We conclude that children who are not brought for outpatient appointments may be at risk of avoidable ill health and that ways of either ensuring attendance at outpatient clinics or providing alternative means of health supervision are needed. PMID- 2317067 TI - Pharmacokinetics of prednisolone in children with nephrosis. AB - The pharmacokinetics of prednisolone given intravenously were studied in 11 children with relapsed steroid responsive nephrotic syndrome, and four control subjects. The clearance of both total and unbound drug was decreased in these children and the unbound fraction of the drug in plasma was significantly correlated with the degree of hypoalbuminaemia. We conclude that changes in the clearance of prednisolone and altered protein binding might account for some of the variability in both therapeutic responses and the incidence of toxicity in patients treated with standard dosage regimens. PMID- 2317068 TI - Who's in CHARGE? Multidisciplinary management of patients with CHARGE association. AB - Clinical experience of 50 patients with the CHARGE association is reviewed and problems with management of children born with multiple system involvement is highlighted. It was found that the outlook for survival was poor if more than one of the following three features was present: cyanotic cardiac lesions, bilateral posterior choanal atresia, or tracheo-oesophageal fistula. Mortality was largely due not to the structural heart defects or choanal abnormalities, but reflected underlying pharyngeal and laryngeal incoordination, which resulted in aspiration of secretions. Outcome is likely to be improved if collaboration between specialist surgical teams allows necessary procedures to be performed using the minimum number of anaesthetics. Examination of both the short and long term management of these children has stressed the importance of a multidisciplinary approach to their care. PMID- 2317069 TI - Iron in tubewell water and linear growth in rural Bangladesh. AB - The growth of 694 children from rural Bangladesh was studied. Children drinking water containing greater than 1 mg iron/l (n = 628) were significantly taller than those drinking less than 1 mg iron/l (n = 66): their mean (SD) height for age Z score was -2.10 (1.34) compared with -2.45 (1.24), p less than 0.05. This suggests that iron deficiency may contribute to growth retardation in poor communities. PMID- 2317070 TI - The five year school medical--time for change. AB - School medical records of 1000 children born in 1981 were studied retrospectively. They showed that once known medical problems and those screened for by the school nurse (hearing, vision, growth) were excluded, only 17 problems requiring treatment were discovered: speech (n = 10), development (n = 3), undescended testes (n = 3), and phimosis (n = 1). This indicates that routine screening by a nurse, backed up by selective medical examination by the school doctor, is efficient and effective. PMID- 2317071 TI - Isolated fructose malabsorption. AB - A patient with isolated fructose malabsorption presented with diarrhoea and colic during the first year of life and subsequently responded to a fructose free diet. Fructose malabsorption has been implicated in some cases of irritable bowel syndrome in adults and may also be an infrequently recognised cause of gastrointestinal symptoms in children. PMID- 2317072 TI - Dietary management of D-lactic acidosis in short bowel syndrome. AB - Manipulation of carbohydrate intake was used to treat severe, recurrent D-lactic acidosis in a patient with short bowel syndrome. Dietary carbohydrate composition was determined after assessment of D-lactic acid production from various carbohydrate substrates by faecal flora in vitro. This approach may be preferable to repeated courses of antibiotics. PMID- 2317073 TI - Atopic eczema, hyponatraemia, and hypoalbuminaemia. AB - We describe an infant with atopic eczema, treated with homoeopathic medicines, who presented with erythema and limb oedema. Concentrations of urinary and plasma sodium and plasma albumin were low. On conventional treatment he made a satisfactory recovery. PMID- 2317074 TI - Growth failure secondary to moyamoya syndrome. AB - We describe a boy who presented at the age of 7 years with short stature due to hypopituitarism. Six months after starting appropriate hormone replacement treatment at the age of 8 he suffered his first generalised convulsion. Further neuroradiological investigation led to the diagnosis of moyamoya syndrome. PMID- 2317075 TI - Staphylococcus epidermidis and retention of neonatal percutaneous central venous catheters. AB - The percutaneous insertion of central venous catheters has become an established practice on many neonatal units. We describe four low birthweight babies, whose catheters became tethered in the vein, and discuss the management of this unusual complication. PMID- 2317076 TI - Cryptosporidiosis and acute leukaemia. AB - Six children with cryptosporidiosis, concurrently receiving chemotherapy for acute leukaemia (n = 5) and lymphoma (n = 1), are described. Two died with evidence of persistent infection. Modification of the chemotherapy regimens in the other four children was associated with successful eradication of the pathogen and permitted continued treatment of the primary disease. PMID- 2317077 TI - Management of acute upper airway obstruction in an intensive care unit in a district general hospital. PMID- 2317078 TI - Intravenous immunoglobulin in HIV infection. PMID- 2317079 TI - Breath hydrogen excretion in infants with colic. PMID- 2317080 TI - Stereographic analysis of syringomas. AB - To investigate biological characteristics of syringomas, three-dimensional (3-D) architectures of epithelial tumor nests and luminal structures of syringomas, hair follicles, and epidermal basement membrane in skin lesions were reconstructed using a computer stereographic analysis. Each lesion was composed of many spherical- to ovoid-shaped tumor nests, which interconnected with each other by narrow tumor strands, showing features of ginger roots or budding fungi. Small discrete tumor nests were often present in the peripheral areas of the lesions. Tumor nests developed around hair follicles and beneath epidermis, but they were never connected with hair follicles or epidermal basement membrane, although occasionally such structures were slightly bent by a pressure from the developing tumor nests. There was no relationship between tumor nests and normal sweat glands. Many tumor nests formed luminal structures; however, some small tumor nests did not. Most of the luminal structures were disconnectedly present. These findings suggest that in each lesion syringoma may occur in a single focus in the upper dermis without a relationship to the surrounding normal epithelial tissues, develop and partly swell forming lumina, and then the peripheral parts of the tumor may become discrete. The ratio of [lumen volume/tumor nest volume] measured by computer stereometry was 0.275 +/- 0.037 (n = 5); this indicates a constant ability to form luminal structures by syringoma cells. PMID- 2317081 TI - Intranuclear androgen and cytosolic receptor concentrations in the axillary skin of osmidrosis. AB - 5 alpha-Dihydrotestosterone (DHT) and testosterone were measured by radioimmunoassay in the crude nuclear and cytoplasmic fractions of the axillary skin of both male and female patients with osmidrosis and the levels compared with those of nongenital skin. The intranuclear levels of DHT were 1.44 +/- 0.22 and 1.77 +/- 0.38 pg/micrograms DNA in men and women, respectively. Those of testosterone were about 10% of DHT levels. In the skin of nontarget regions nuclear DHT was much scarcer or undetectable. Cytosolic androgen receptors in isolated apocrine glands were also measured using 3H-R1881 as a ligand. Typical androgen receptors were present in all of eight patients (KD = 1.32 +/- 0.24 X 10(-9)M, Bmax = 10.3 +/- 0.51 fmol/mg protein). Neither the intranuclear androgen concentrations nor the cytosolic androgen receptor levels were significantly different between the two sexes. These data indicate clearly that the apocrine gland of patients with osmidrosis is a typical androgen target organ, irrespective of sex, and suggest that nuclear DHT in the axillary skin of women is derived from not only testosterone but also other precursors, especially in consideration of the very low serum concentrations of testosterone in females. PMID- 2317082 TI - The inhibiting effect of PABA on photocarcinogenesis. AB - The efficacy of a 5% solution of para-aminobenzoic acid (PABA) to protect against photocarcinogenesis was tested in 6 groups, each of which contained 30 light pigmented hairless mice. The light source was a Phillips TL 40 W/12, which mainly emits UVB. PABA significantly retarded the tumor induction time (p less than 0.05) and reduced both tumor yield and carcinoma yield (p less than 0.05). The dorsal skin of the mice was removed and weighed. The mean weight of UVR-exposed mice skin protected with PABA did not differ from that of the controls, but in the non-protected UVR-exposed mice the skin samples were significantly heavier (p less than 0.05). PMID- 2317084 TI - Are free radicals and not quinones the haptenic species derived from urushiols and other contact allergenic mono- and dihydric alkylbenzenes? The significance of NADH, glutathione, and redox cycling in the skin. AB - The induction of allergic contact dermatitis to urushiols from poison ivy and related plants is generally believed to involve an initial oxidation event by which a protein-reactive quinone is formed. However, this does not readily account for the contact allergenicity of closely related mono- and dihydric alkylbenzenes such as the alkylphenols and alkylresorcinols which are not so easily oxidised to quinones in vitro. When the redox processes known to occur in living tissues are taken into consideration, a more plausible unifying mechanism involving the formation of protein-reactive radical species becomes apparent. Experiments described here examine the autoxidation of p-benzoquinone and various mono- and dihydric benzenes and alkylbenzenes, and their reactions with the diphenylpicrylhydrazyl radical, cysteine, glutathione, and NADH. We have also demonstrated that administration to mice of 2-oxo-4-thiazolidine carboxylate, a compound known to elevate intracellular glutathione levels, inhibits the irritancy and sensitising activity of 3-pentadecylphenol. This work suggests that redox cycling in the skin following penetration of allergenic mono- and dihydric alkylbenzenes initially depletes local levels of endogenous reducing equivalents such as glutathione and NADH; once depleted, further cycling results in the uncontrolled generation of radical species which may reasonably be expected to exhibit protein reactivity. PMID- 2317083 TI - Multifunctional analysis of the interaction of anthralin and its metabolites anthraquinone and anthralin dimer with the inner mitochondrial membrane. AB - We studied the interaction of the antipsoriatic compound anthralin (1.8-dihydroxy 9-anthrone), and its metabolites anthraquinone (1.8-dihydroxy-9.10-anthraquinone) and anthralin dimer (1.8.1'.8'.-tetrahydroxy-10.10'-bis-9[10]-dianthrone) with the inner mitochondrial membrane. Mitochondrial membrane functions such as ubiquinone redox equilibria, redox status of iron sulfur clusters, cyanide sensitive and cyanide-insensitive oxygen consumption, adenosine triphosphate (ATP) synthesis, ATP hydrolysis, and adenine nucleotide content of mitochondria were analyzed. Anthralin is an inhibitor of mitochondrial oxygen uptake in the presence of ADP and substrate (cyanide-sensitive respiration), inhibits ATP synthesis without affecting ATP hydrolysis, and depletes mitochondria of ATP. Anthralin dimer is a much weaker inhibitor of mitochondrial functions and anthraquinone is almost inactive. Anthralin, but not anthraquinone and anthralin dimer, reverses uncoupler stimulated oxygen consumption, stimulates cyanide insensitive respiration, reduces mitochondrial ubiquinone-9 and -10 to the corresponding ubiquinols and reduces mitochondrial iron sulfur clusters. Anthralin may induce formation of reactive oxygen species by enhancing autoxidation of mitochondrial components and/or by catalyzed oxidation of anthralin. Taken together, anthralin acts as an electron donor to inner mitochondrial membrane associated redox components, inhibits the electron transport chain, and has an oligomycin-like effect. Anthralin dimer and anthraquinone do not function as electron donors and act by a different reaction mechanism. Respiratory measurements in human keratinocytes revealed similar results as obtained with isolated mitochondria. We suggest that modulation of membrane redox status may be a common concept of anthralin action in target cells such as keratinocytes and neutrophils. PMID- 2317085 TI - Elevated serum IgE, eosinophilia, and lung function in rubber workers. AB - We previously reported an outbreak of acute respiratory illness associated with eosinophilia in a group of rubber workers who performed a thermoinjection process in which synthetic rubber was heated and then injected onto metal molds. This study was conducted to determine if persistent respiratory health effects were associated with this work area and to explore the possible allergic etiology of this syndrome. A survey was performed 1 mo after a major improvement in area ventilation and consisted of baseline, cross-shift, and cross-week spirometry; diffusing capacity; serum immunoglobulin E (IgE), total eosinophil count; and skin patch testing. Baseline lung function, cross-shift, and cross-week spirometry were not significantly worse in the exposed group as compared to the control group. However, either eosinophilia (greater than 450/mm3) or elevated serum IgE (greater than 470 ng/ml) were present in 44% of exposed workers vs. 11% of the control group (p = .003). Nine months later, neither eosinophilia nor elevated IgE were associated with employment in this work area. We conclude that employment in the thermoinjection process was associated with eosinophilia and elevated IgE, which suggests sensitization to one of the components of the rubber, although no effect on pulmonary function could be demonstrated. PMID- 2317086 TI - Effects of chronic organic dust exposure on respiratory function and airway responsiveness in peat moss factory workers. AB - Fifty-two males and 1 female, who were 19 to 62 y of age (median = 26), were employed at an eastern Quebec peat moss plant and were included in this study. Of these 53 workers, 29 were smokers, 5 were ex-smokers, and 19 had never smoked. The workers were divided by level of exposure into 4 groups: (1) group 1--minimal exposure (N = 7); (2) group 2--light exposure (N = 7); (3) group 3--moderate exposure (N = 17); and (4) group 4--heavy exposure (N = 22). Chest radiographs and physical examinations were normal for all subjects. Only 1 subject had precipitins to Penicillium and Monocillium species isolated from the peat moss plant. Pulmonary function tests were normal and similar in all groups. Thirty three subjects (20 smokers, 4 ex-smokers, and 9 nonsmokers) had chronic bronchitis; these symptoms were related to work exposure for 28 subjects. Bronchial responsiveness to methacholine was measured in 14 subjects who had persistent cough and sputum. No subject had evidence of airway hyper responsiveness, i.e., PC20 metacholine less than 8 mg/ml. We concluded that the peat moss workers in our study showed no evidence of extrinsic allergic alveolitis; however, chronic exposure to organic dust leads to chronic cough and sputum production, which is not associated with significant lung impairment nor increase in nonspecific airway responsiveness. PMID- 2317087 TI - Long-term observation of serum creatinine and arterial blood pH in persons with cadmium-induced renal dysfunction. AB - Twenty-one subjects who had cadmium (Cd)-induced renal dysfunction and who lived in a Cd-polluted area in Japan were investigated to determine changes in their renal function. Since 1974, serum creatinine and arterial blood pH were measured annually during the autumn months for 9-14 y. Mean serum creatinine was significantly increased during this period, i.e., from 1.19 +/- 1.28 mg/100 ml to 1.68 +/- 1.56 mg/100 ml. Even after cadmium exposure ceased, significant deterioration of glomerular filtration was found. Eleven subjects showed a greater than 20% serum creatinine increase during this period. The most severe case had a serum creatinine value of 4.4 mg/100 ml at the most recent examination and experienced generalized edema, which suggests a clinical diagnosis of renal failure. The mean arterial blood pH values decreased significantly in all subjects, i.e., from 7.400 +/- 0.023 to 7.361 +/- 0.034. The 11 subjects cited above also showed a significant decrease and progression of tubular dysfunction after Cd exposure ceased. Our findings suggest that Cd-induced renal tubular dysfunction and decreased glomerular filtration are aggravated even after cessation of environmental Cd exposure, and in some cases this renal dysfunction may progress to renal failure. PMID- 2317088 TI - Temporal fluctuation of the lead level in the cord blood of neonates in Taipei. AB - From August 1985 to September 1987, 9,502 cord blood samples were obtained from the Taipei Municipal Maternal and Child Hospital. A total of 205 cord blood samples chosen randomly from newborns without parental exposure to lead were analyzed by flameless atomic absorption spectrophotometry. The average blood lead level was .36 +/- .11 mumol/l (7.48 +/- 2.25 micrograms/dl). A similar analysis was performed on samples obtained from 160 newborns whose fathers had occupational lead exposure. In both groups, the average concentration of lead in cord blood in the summer was statistically greater than that in the winter. Air lead and total amount of lead in gasoline consumed in Taipei appeared to be associated with this seasonal fluctuation in the average lead level of cord blood. After considering alternative sources, we conclude that the seasonal fluctuation of cord blood lead is probably influenced by air lead produced from the combustion of gasoline. PMID- 2317089 TI - Birthweight of infants born to Hispanic women employed in agriculture. AB - A prospective study examined the effects of maternal occupation on the birthweight of infants of Hispanic women. The study population consisted of 1,040 pregnant women enrolled for prenatal care in two rural health care centers in California between 1982 and 1984. Birthweights of infants were examined after classifying these women into three groups: (1) 255 mothers who did agricultural work, (2) 134 mothers who worked in nonagricultural jobs, and (3) 651 mothers who did not work during pregnancy. Prenatal interviews and medical records revealed medical, social, and occupational histories of the mothers. Stepwise linear regression analyses, using the backward elimination method, were conducted for some exposure models to determine whether work category influenced birthweight after controlling for confounders. The incidence of low birthweight and mean birthweights did not vary significantly with work status. PMID- 2317090 TI - Prevalence and antibiogram of Campylobacter jejuni in domestic animals in rural Ghana. AB - A total of 134 samples of rectal and cloacal swabs taken from apparently healthy domestic animals that were in 43 of 76 homes located in rural Ghana were examined for Campylobacter jejuni. C. jejuni was isolated from 32.8% (44/134) of the animals. The highest isolation rate of 43.6% was from local domestic fowls, followed by goats (33.3%) and sheep (23%). This organism was not detected in the pigs, cats, and ducks. All 44 strains of this bacterium produced hydrogen sulphide and hydrolyzed hippurate; antibiogram on 24 strains showed resistance to cephalothin, cephalexin, and sulfamethoxazole/trimethoprim. C. jejuni biotype 2 is the prevailing strain in animals in the area studied. PMID- 2317092 TI - You cannot publish the same paper twice. PMID- 2317091 TI - Our industries and our lives: a view from Nigeria. PMID- 2317093 TI - Client-centered case consultation and single-case research design: application to case management. AB - Tim is a 17-year-old white, male adolescent who exhibited extreme social isolation and was unresponsive to multiple forms of treatment. Staff members had conflicting views about the nature of Tim's difficulties; these conflicting views indicated their loss of objectivity. Using client-centered case consultation and single-case research design, the consultant helped staff members regain their objectivity so they might intervene to reduce Tim's social isolation. PMID- 2317094 TI - A future perspective on psychiatric mental health nursing. PMID- 2317095 TI - Psychiatric nursing in the 1990s. AB - This article reviews the accomplishments of psychiatric nursing--theory development, advanced practitioner roles, family-centered care--and notes some limitations--a projected shortage of psychiatric nurses, devaluation of biological knowledge, reluctance to focus on illness. The challenges ahead for the 1990s are described with a focus on the tremendous need to integrate the biological sciences (neurobiology, genetics, and immunology) and behavioral sciences in the practice of psychiatric nursing. In the development of these issues, attention is paid to the argument raised by consumer advocacy groups that a clear differentiation exists between adjustment problems and mental illness. In a time when psychiatry is realigning itself with medical practice, it is important that psychiatric nursing become reassociated with both neurological nursing and the care ethic. This article ends with a partial list of questions for psychiatric nurses to answer in the decade ahead. PMID- 2317096 TI - Psychobiological indices of bipolar mood disorder: future trends in nursing care. AB - Recent research on the various biological indices of bipolar mood disorder reveals a complex framework for the understanding of this psychobiological disorder. Four major constructs emerge from the professional literature to form the basis of the current understanding of and approaches to bipolar disorder. The first construct is that of biological rhythms and mood disorders. From this perspective, time is considered as a biological dimension evidenced by biological rhythms. Disruption of certain internal circadian rhythms yields behavioral change and symptoms of psychobiological disequilibrium. Concepts inherent in this particular construct include sleep, effect of light on mood pattern, and possible biochemical indices of mood modulation such as melatonin or phenylethylamine. The second construct attempts to explore the linkage between biochemical brain function and aberrant mood behavior. This information bifurcates into two major categories: (1) effects of psychopharmacological substances on neurotransmitter synthesis and release; and (2) implications of dietary influences on neurotransmitter activity and the psychobiological ramifications of such activity on the clinical understanding of the behavioral disorder. An eclectic set of concepts form the third construct in the framework presented here. These concepts address other possible etiological or mitigating biological influences on bipolar mood states. Such influences include, but are not limited to, limbic seizure activity, neuroendocrine dysfunction, and organic substrates of bipolar states such as various malignancies. The final construct explores the role of genetics in either the predisposition to or the emergence of bipolar mood disordered states. This report will focus on a review of the aforementioned constructs, pointing to significant research and narrative professional publications. In addition, the presentation will address the application of the nursing process to psychobiological aspects of bipolar mood disorder, specifically circadian rhythmicity disturbance and dietary influences on neurotransmission. PMID- 2317097 TI - Alzheimer's disease: a disabling neurophysiological disorder with complex nursing implications. AB - Alzheimer's Disease (AD) is a very complex and devastating disorder of the brain that affects over 2 million people in the United States, mostly over age 65. Approximately one-half are taken care of at home by family members; the remainder are in institutions. Nearly 120,000 deaths are attributed to AD annually. While biomedical research continues to make headway in uncovering factors related to the disease, the causes, and therefore, the treatment remain just beyond our reach. In the meantime, persons with AD, their family members, and professional caregivers must learn to cope with this disabling disease on a day-to-day basis while waiting for a breakthrough. AD is characterized by a gradual decline in mental status and functional abilities over an extended period of time, from as short as 1 year to as long as 10 years or more. Eventually, all components of cerebral functioning are altered, with the neuronal losses exhibited at the cognitive and behavioral level. The nature and degree of decline depends on the extent of the progression of neuronal deterioration and, therefore, varies widely from patient to patient. The complex interactional patterns of pathophysiological brain changes and the concomitant cognitive/behavioral manifestations present careplanning and caregiving dilemmas. On the one hand, it is our responsibility as nurses to treat patients and teach others to care for patients in the least restrictive environment possible, while maintaining a choice of options, promoting optimal functioning, and fostering independence in the patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317099 TI - Collaboration in care and research. AB - This article focuses on psychiatric mental health nursing care and research, with particular attention to collaboration with other health professionals in the area of geriatric mental health. Various components of the NIMH Task Force on Nursing report and recommendations are emphasized. These include research focused on: (a) improving the understanding, treatment, and rehabilitation of the mentally ill; (b) preventing mental illness and promoting mental health; (c) continuous care of persons who are acutely or chronically mentally ill or who are at risk for mental illness; (d) therapeutic interventions with ill persons or those at risk; and (e) the design, implementation, and evaluation of new and existing models of care delivery. An illustrative model of research in geriatric mental health nursing is presented. Particular attention is given to collaborative relationships developed by the primary nursing research team and the nursing staff in an acute care setting, colleagues providing nursing home care, and physician colleagues in geriatric mental health, gerontology, and neurology. Strategies to enhance collaboration and develop collegial relationships for better patient care are presented. PMID- 2317098 TI - Early family experiences of women with bulimia and depression. AB - This study characterizes the early family experiences of 30 women with bulimia nervosa and 15 women with major depression, and compares them with 100 women controls, with particular emphasis placed on parental rearing practices, family conflict resolution, sexual mistreatment, problematic childhood indicators, and childhood separation experiences. There is little research on these patient populations in relation to their childhood experiences, and thus, it is difficult to identify markers for women at risk for these disorders. The findings show that there are significant differences between the experiences these women had growing up and those of the control group, and a profile of children at risk based upon the study indicators is presented. PMID- 2317100 TI - Collaborative investigation of adult children of alcoholics with anxiety. AB - The literature reports an increased incidence of anxiety disorders in alcoholic families. Whether anxiety is a complication of alcoholism or a precursor to alcohol abuse is not understood. Studies suggest that there are psychological as well as genetic components in substance abuse and anxiety disorders. The purpose of this paper is to describe a collaborative effort designed to explore the complex interaction between the etiologic factors that lead to anxiety and substance abuse. This collaboration brings together the unique perspectives of both psychiatric medicine and psychiatric nursing. PMID- 2317101 TI - Genetic implications for major affective disorders. AB - This article reviews the current outcomes of twin, adoption, and family epidemiological studies. Psychiatric genetics research has made a major paradigm shift from epidemiology studies to molecular genetic research. The manner in which affective disorders are inherited continues to elude scientists. Nurses, in collaboration with patients, families and scientists, can facilitate the research process. Merging our professional caring with the biological research outcomes will assure our professional contribution in this expanding research and assist the affected persons from further stigmatization. PMID- 2317102 TI - Hemodialysis of HIV-positive patients: impact on organization and staff. AB - Hemodialysis of HIV-positive patients poses a new challenge to dialysis facilities. Organizations need to address treatment options, staffing issues, and occupational risks as programs for treatment of these individuals are developed. This article presents an overview of these concerns and one facility's experience. PMID- 2317103 TI - Renal disease and HIV infection: clinical course, treatment outcome, and infection control. AB - The AIDS epidemic is growing worldwide, and projections for the next decade indicate that over 6 million people will develop clinical AIDS, an increase of 10 30 times the number that has been reported to date. AIDS is spreading rapidly among intravenous drug abusers, which is the risk group that is at highest risk for the development of HIV associated nephropathy (HIVAN). This will result in an increase in the number of patients who develop end stage renal disease (ESRD) and require dialysis treatment during the next decade. Survival time for patients with AIDS is improving as new therapies are implemented; the prognosis for patients with AIDS and ESRD also appears to be slightly better, but the natural course of HIV infection in the ESRD patient remains to be defined. PMID- 2317104 TI - A miraculous recovery following life-threatening complications. PMID- 2317105 TI - The relationship between chronological age and perceived quality of life of hemodialysis patients. AB - This descriptive study examined the relationship between age and perceived quality of life of chronic hemodialysis patients. The quality of life score and the chronological age of the 17 hemodialysis patients were correlated. No significant relationship was established between the ages of the patients and how they perceived the quality of their lives. PMID- 2317106 TI - Maintaining quality patient care while increasing staff safety: AIDS update. AB - As nurses, our belief is that not enough is known regarding AIDS or the HIV virus that causes it and because of this, concern among health care workers is justified. Prompted by this concern, we developed a protocol that we think will help improve staff safety while maintaining quality patient care. We are sharing our ideas as this concern affects all nephrology personnel. The intention of this article is to enable others in this field to establish a protocol based on their own individual situations and needs. PMID- 2317107 TI - Case management of the anemic patient. Focus on blood pressure and rHuEPO therapy. AB - As the use of Epoetin alfa to treat the anemia of chronic renal failure (CRF) expands, nurses play an ever-increasing role in patient monitoring and control. One area that relies heavily on nurses is blood pressure monitoring. Clinical trials with Epoetin alfa in hemodialysis patients indicate that its use may be associated with the onset or aggravation of elevated blood pressure as the hematocrit level increases. Because high blood pressure is a risk factor for left ventricular hypertrophy and cardiovascular mortality in this patient population, use of an agent that may cause high blood pressure requires careful monitoring. As the following two cases reports illustrate, sufficient data to provide better insight into the clinical aspects of this potential problem have now been accumulated. PMID- 2317108 TI - Let's hear it for nursing. PMID- 2317109 TI - AIDS patient--knowledge and compassion needed. PMID- 2317110 TI - Phenotypic and genotypic analysis of mononuclear cells from patients with Felty's syndrome. AB - Phenotypic and genotypic characteristics of the peripheral blood mononuclear cells in nine patients with Felty's syndrome have been examined. One patient had an increased number and percentage of peripheral blood mononuclear cells with the phenotype CD3+ Leu-7+ CD16+ and showed a clonal rearrangement of the T cell receptor B chain gene. The remaining eight patients all showed a germline configuration of the T cell receptor B chain gene. In two patients an increased proportion of CD3+ Leu-7+ CD16- peripheral blood mononuclear cells (45 (SD 11)% of peripheral blood mononuclear cells) were found, while the remaining six patients had proportions of CD3+ Leu-7+ cells similar to those of patients with uncomplicated rheumatoid arthritis. These data confirm that patients with Felty's syndrome are heterogeneous, with at least three different peripheral blood mononuclear cell phenotypic subsets. One subset is characterised by a clonal expansion of an unusual lymphocyte subpopulation, another by polyclonal expansion, and the third subset has the same proportions of peripheral blood mononuclear cells as patients with uncomplicated rheumatoid arthritis. PMID- 2317111 TI - Infective endocarditis, rheumatoid factor, and anticardiolipin antibodies. AB - Serum samples from 22 patients with infective endocarditis were analysed for the presence of antibodies to cardiolipin, false positive Venereal Disease Research Laboratory (VDRL) test, and rheumatoid factor in order to determine the prevalence of anticardiolipin antibodies, their level, and to ascertain whether there was any correlation with the presence of rheumatoid factor. Although the latex test was positive in 10/22 (45%) patients, anticardiolipin antibodies, usually of a low level, were raised in only four (18%), and the VDRL test was positive in two patients in whom other antibodies were negative. These results show a clear discordance between these three tests, indicating that B cell production of these antibodies is separate and distinct. As with other infections which result in anticardiolipin antibody production, no thrombotic events were encountered. PMID- 2317113 TI - A subset of systemic lupus erythematosus with progressive cystic bone lesions. AB - Clinical and serological findings of 16 patients with systemic lupus erythematosus (SLE) who had progressive cystic bone lesions were compared with a control group of 19 patients with SLE without radiological evidence of bone cysts. Central nervous system manifestations, synovitis, and other radiologically observed skeletal abnormalities were more prevalent in the patients with cysts than in the control group. Higher concentrations of C reactive protein, and a greater incidence of rheumatoid factor positivity were seen in the patients with cysts than in the control patients, but no other serological differences were found. It is suggested that patients with SLE with progressive cystic lesions form a subgroup of the syndrome characterised by an increased acute phase reaction. PMID- 2317112 TI - Neuropsychiatric lupus erythematosus, cerebral infarctions, and anticardiolipin antibodies. AB - Anticardiolipin antibody (aCL) has been associated with thromboembolic phenomena, including stroke, in certain patients with systemic lupus erythematosus (SLE); however, the relation between this antibody and the central nervous system manifestations of SLE is unknown. Serum samples and cerebrospinal fluid from five patients with SLE and acute central nervous system manifestations were assayed for the presence of aCL. Anticardiolipin antibody was identified in sera from four of the five patients but in none of the cerebrospinal fluid samples. Nuclear magnetic resonance imaging showed 'infarct-like' lesions in these four patients. This preliminary study suggests that a correlation between serum aCL and cerebral infarcts in central nervous system lupus may potentially exist. From this limited study it seems unlikely that aCL has a direct pathogenic role in the diffuse encephalopathy of acute central nervous system lupus. PMID- 2317114 TI - Partial purification and characterisation of a synovial fluid inhibitor of osteoblasts. AB - A polypeptide inhibitor of osteoblast proliferation is described which occurs in synovial effusions of patients with rheumatoid arthritis. Partial purification of the inhibitor showed a molecular weight of approximately 81,000 by gel electrophoresis. This polypeptide seems to be unique as no inhibitor of osteoblasts of similar molecular weight has been previously described in rheumatoid synovial effusions. PMID- 2317115 TI - Influence of indomethacin on extracellular calcium homeostasis. AB - Rheumatoid arthritis is associated with a generalised loss of bone mass. One of the factors that have been implicated in the pathogenesis of this bone loss is the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs are known to increase gastrointestinal permeability and may thus influence the absorption of calcium; they may also influence glomerular filtration rate and the renal excretion of calcium; in addition, NSAIDs may inhibit osteoblast function as well as osteoclastic bone resorption. Calcium homeostasis was studied in eight healthy volunteers during eight days' treatment with 150 mg indomethacin daily. No changes in serum concentration of calcium, phosphorus, parathyroid hormone, 25 hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were found. The creatinine clearance and the urinary excretion of phosphorus and sodium did not change, but a decrease in calcium excretion was noted (mean (SEM) calcium/creatinine excretion 0.52 (0.05) v 0.28 (0.06)). This decrease is probably due to renal retention of calcium. Whether this decrease of urinary calcium excretion has a positive or a negative effect on bone is presently unknown. PMID- 2317117 TI - Anticardiolipin antibody negative occlusive vascular retinopathy in systemic lupus erythematosus. PMID- 2317116 TI - The time of blood sampling for osteocalcin determinations. PMID- 2317118 TI - Beneficial effects of reduced intake of polyunsaturated fatty acids in the diet for one year in patients with systemic lupus erythematosus. PMID- 2317119 TI - Peyronie's disease in systemic sclerosis. PMID- 2317120 TI - Arthritis in acute febrile neutrophilic dermatosis (Sweet's syndrome) PMID- 2317121 TI - Measurement of joint inflammation in rheumatoid arthritis with indium-111 chloride. AB - Studies in the collagen and rabbit models of arthritis have indicated that indium 111 chloride (111InCl3) scintigraphy objectively measures synovial inflammation. Indium-111 chloride scans, with imaging three days after 19 MBq intravenous injection, were performed on 21 patients with definite or classical rheumatoid arthritis (RA), all of whom were functional class II. Standard clinical indices of disease activity were recorded at the time of imaging by the same investigator, who was unaware of the results of joint scans. In addition, eight patients with severe osteoarthritis, four of whom were considered to need hip or knee joint replacement, were similarly scanned. In each patient 16 joints were graded as 0 to 5, based on increasing degrees of 111InCl3 uptake, by a single investigator blinded to the patient's diagnosis and clinical status. In the group with RA significant correlations were observed between individual joint uptake on scan and peripheral joints with swelling, joints reported to be painful, and joints with any abnormality on physical examination. In the group with osteoarthritis joints positive on scan correlated with the presence of pain. A total scan score (sum of individual joint scores) was calculated for each patient. In the patients with RA values ranged from 0 to 42 with a mean (SEM) of 20.7 (2.7) and correlated with the number of swollen joints and decreasing grip strength. In the group with osteoarthritis the mean total scan score (9.2 (1.5), range 3-14) was significantly lower than in the patients with RA. These data show that 111InCl3 scanning can measure joint involvement by RA. PMID- 2317122 TI - Anaemia in rheumatoid arthritis: the role of iron, vitamin B12, and folic acid deficiency, and erythropoietin responsiveness. AB - Thirty six patients with rheumatoid arthritis (RA) (25 with anaemia) were studied to establish the role of iron, vitamin B12, and folic acid deficiency, erythropoietin responsiveness, and iron absorption in the diagnosis and pathogenesis of anaemia in RA. Iron deficiency, assessed by stainable bone marrow iron content, occurred in 13/25 (52%), vitamin B12 deficiency in 7/24 (29%), and folic acid deficiency in 5/24 (21%) of the anaemic patients. Only 8/25 (32%) had just one type of anaemia. The iron deficiency of anaemia of chronic disease (ACD) was distinguished by ferritin concentration, which was higher in that group. Mean cell volume (MCV) and mean cell haemoglobin (MCH) were lower in both anaemic groups, but most pronounced in iron deficient patients. Folic acid, and especially vitamin B12 deficiency, masked iron deficiency by increasing the MCV and MCH. Iron absorption tended to be highest in iron deficiency and lowest in ACD, suggesting that decreased iron absorption is not a cause of ACD in RA. No specific causes were found for vitamin B12 or folic acid deficiency. Haemoglobin concentration was negatively correlated with erythrocyte sedimentation rate in the group with ACD. Erythropoietin response was lower in ACD than in iron deficient patients. It was concluded that generally more than one type of anaemia is present simultaneously in anaemic patients with RA. The diagnosis of each type may be masked by another. Studies on pathogenesis of the anaemia are difficult as deficiencies generally coexist with ACD. Disease activity and, possibly, erythropoietin responsiveness are major factors in ACD pathogenesis. PMID- 2317123 TI - [Results of forensic medicine victim/perpetrator studies following sex offenses]. AB - 39.1% of all clinical examinations performed at the institute for legal medicine in Hannover during a period of 9 years were carried out after sexual assault (229 out of 585 cases between 1979-1987). In 74.4% of all women extragenital injuries and in 26.2% of the cases genital lesions could be observed. Vaginal swabs showed sperm at a rate of 44%; spermatozoa could be observed at a maximum delay between assault and examination of 36 hours. Three male victims of sexual assaults and 37 male defendants were examined. On male victim presented superficial lesions of the anus. In 27 penis swabs there could be found spermatozoa (4x), vaginal epithelia (2x) and red blood cells (1x; after intercourse during menstruation). PMID- 2317124 TI - [Species differentiation by placental morphology with human and animal tissue. A contribution to species determination in relation to embryo findings]. AB - On the occasion of an embryo being found with attached placenta, species differentiation of the fetus was to be carried out within the framework of a preliminary proceeding. Consulted gynecologists diagnosed a human embryo. From the macroscopic and histologic structure of the placenta, our investigations resulted a species diagnosis of an embryo belonging to the order Carnivora (cat). The diversity of external placental shapes as well as of different histologic structures permit species differentiation. The delimitation of the human embryo from nonhuman tissue should always be possible, even on formalin-fixed material. PMID- 2317125 TI - [Identification of blood stains and fetal tissue using genetic fingerprinting]. AB - Two cases from practical forensic serological investigations which could not be clarified by means of conventional serological methods, but could be resolved on the basis of the DNA finger print technique with oligonucleotide probes are presented. Both the comparison of the identity of the blood sample which had been stored for a long time and the determination of paternity in fetal material in a case of incest demonstrate the enormous possibilities of this method. However, some problems which still have not been resolved at least at present with regard to the evaluation and appraisal of the band patterns are also discussed. PMID- 2317126 TI - Quantitative and functional restorations and alterations of peripheral lymphocytes in patients with autologous spleen implantation. AB - To reduce the risk of severe infections in splenectomized patients, new methods for splenic preservation or heterotopic autologous spleen implantation have been established. In the latter case, the immunological and functional benefits are still under discussion. In this study we compared immunological parameters in 16 splenectomized patients with and without heterotopic autologous spleen implantation with a nonsplenectomized control group. The total lymphocyte counts- T-cells, CD4+ -, as well as CD8+ - lymphocytes, CD16+ - and B-cells--were highly elevated in both groups, whereby the B-cells were relatively and absolutely higher in the implanted group than in the nonimplanted group. Splenectomized patients had a significantly reduced serum IgM level. The serum IgM of patients with splenic autotransplantation was not significantly lower than that of the controls. In contrast to the impaired in vitro immunoglobulin synthesis in the splenectomized group, the autotransplanted patients showed a normal PWM-induced IgG and IgM synthesis and an increased IgA production compared with the controls. The latter results support the findings of elevated serum IgA levels in this group. The mitogenic-induced proliferation with PHA, ConA, PWM, and OKT3 was not clearly different within the tested groups. The results may indicate a benefit of autologous spleen implantation in regard to the humoral immune response. PMID- 2317127 TI - Bilateral pseudarthrosis of the femur after stress fracture. AB - Stress fractures of the diaphysis of the femur are very rare, particularly bilateral ones. We describe here a woman patient with bilateral pseudoarthrosis of the femoral diaphysis which was the result of a stress fracture. The case is a rarity because the in question is of a dwarfism stature with great deformation of the lower extremities due to rickets. The patient has been closely examined for over 30 years. Our own explanation for the beginnings of stress fracture as well as for the pseudarthrosis development are given. PMID- 2317128 TI - A case of hip osteoarthrosis contaminated by fungi. A histological study. AB - A pathological study of a surgical specimen of hip osteoarthrosis presenting a superficial fungal infection (presumably Aspergillus) without any known origin is reported. Fungal penetration was mild in cartilage and fibrocartilage and more pronounced in naked cancellous bone, but it did not occur in eburnated bone or in the deep osteomedullar area. This observation indicates an unusual combination of infection and osteoarthrosis. Relationships between fungi and bone or cartilage as well as interaction between osteoarthrotic remodeling and a superimposed disease are discussed. PMID- 2317129 TI - The Tikhoff-Linberg procedure for bone tumors of the proximal humerus: the classical "extensive" technique versus a modified "transglenoid" resection. AB - The authors report on two groups of patients (each with 12) with primary bone tumors of the humerus who underwent either a classical Tikhoff-Linberg (T-L) procedure or a modified technique by which the body of the scapula was saved. The latter procedure was an "en bloc" resection of the glenohumeral joint after an extra-capsular osteotomy of the neck of the scapula, followed by reconstruction with a modular prosthesis. Indications, perioperative differences, and complications of both procedures are discussed. Besides producing better aesthetic and functional results, the modified technique offered the advantages of shorter anesthesia time, less blood loss, and a better anchorage of the prosthesis. The results of this study show that the proposed modification of the T-L procedure is indicated in patients with bone tumors of the proximal humerus in which invasion of the joint capsule is present without macroscopic involvement of the glenoid. PMID- 2317130 TI - New aspects of lumbar disc disease. MR imaging and histological findings. AB - Magnetic resonance imaging (MRI) and plain X-ray and CT studies were performed in patients with a history of lumbar back pain due to spinal disc disease. Spin-echo pulse sequences (SE), phase-contrast techniques (partial saturation sequences with delayed readout, PS), and fat-suppressing inversion recovery sequences (STIR) were employed. In 74 of 325 patients, PS and STIR images displayed vertebral marrow changes adjacent to the end-plates of the affected segments. Bacterial infection, however, could be excluded. In six patients histological diagnosis showed substitution of hematopoietic marrow by fatty tissue, cartilaginous particles, degeneration of fat cells, and an increase in extracellular fluid with different components. The etiology is still unclear, but a correlation with lumbar disc disease is demonstrated. These vertebral marrow changes were best displayed with STIR and phase-contrast MR sequences, both providing contrast changes superior to T2-weighted SE techniques. PMID- 2317131 TI - Pathology of the bone-cement interface in loosening of total hip replacement. AB - The histopathology of the bone-cement interface in nine retrieved hip prostheses is reported. Three cases presented features similar to those observed by Charnley in highly successful implants, and they were classified as stable prostheses, although signs of periprosthetic bone resorption were already present. In this group a macrophagic reaction was evident even in the presence of a stable bone cement interface, supporting the view that the release of particles by the cement or by the prosthetic components can precede the mechanical instability and be the primary cause of loosening. In six prostheses the connective tissue layer between the cement and the bone was thick and no bone trabecula reached the cement surface. The polymorphous features of this connective membrane probably resulted from instability and movement at the bone-cement and stem-cement interfaces. On the basis of the pathological changes observed in the study, the process of loosening must be far advanced before it is detected on radiographs; it is suggested that scintigraphy is the best noninvasive technique to demonstrate macrophage activation and increased bone remodeling around the cement in the early phases of loosening. PMID- 2317132 TI - Digital subtraction angiography in musculoskeletal tumors and other conditions. AB - One hundred and forty consecutive DSA examinations of various musculoskeletal diseases were analyzed with respect to the contributions and/or limits of this modern diagnostic imaging modality. Angiography remains the imaging tool of choice for many benign and malignant orthopedic conditions of bones and soft tissues, mainly when MRI is still not generally available. It remains indispensable for embolization and/or local chemotherapy. DSA has the advantage of being less invasive and it also surpasses analog arteriography in better visualization of vascular patterns hidden in hyperostosis, sclerosis, and metallic shadows. Angiographic investigations, when necessary, should therefore start with DSA. PMID- 2317133 TI - Treatment of an old infection in a total hip replacement with an interim spacer prosthesis. AB - When treating a septic hip-joint prosthesis with bone loss of the proximal femur secondary to osteomyelitis, we implanted a specially designed prosthesis to act as a local antibiotic and spacer between the acetabulum and femur until the infection abated. Arthroplasty could then be carried out with no trouble and there was no recurrence of infection. PMID- 2317134 TI - Induction of monocyte chemotaxis in devascularized rabbit bone. AB - Temporary impairment of blood supply has been suggested to cause bone remodeling. The degradation of cells and matrix and the attraction of resorbing cells were examined in this study. Bone specimens of rabbits were stored in vitro for 2-20 days. At the end of this aging process the probes were tested for their chemotactic activity toward autologous leukocytes in a diffusion chamber. Both supernatant from the aged bone specimens and ground bone particles exhibited significant chemotactic activity that was specifically attracting monocytes. It is suggested that soluble bone matrix proteins or degeneration products liberated during ischemic damage to cortical bone initiate the resorptive process. PMID- 2317135 TI - 22nd annual Walter J. Zeiter lecture. Continuing physiatric education and our academy: purpose, past, present, and prospect. PMID- 2317136 TI - Depressed mood in spinal cord injured patients: staff perceptions and patient realities. AB - This study examined the correspondence between staff ratings and patient ratings of depressed mood for 102 newly spinal cord injured persons admitted to two regional spinal cord injury rehabilitation centers. Patients rated their mood by using the Depression Adjective Check List (DACL). Treatment staff also rated each patient by completing the DACL as they thought the patient would have on the same day. Ratings were made every three weeks during a patient's stay. Results indicate that patients were generally similar to the general population in terms of self-rated depressed mood. Staff members typically overestimated levels of patients' depressed moods. Staff members' ratings did correlate significantly, although modestly, with patients' self-ratings (r = .34, p less than .001). However, staff's accuracy in estimating patient mood did not increase as a function of increased exposure to the patient or years of experience in rehabilitation. PMID- 2317137 TI - Atelectasis and pneumonia in acute spinal cord injury. AB - The purpose of this study was to demonstrate the high incidence of atelectasis or pneumonia (A/P) in the left lung of acute spinal cord injured (SCI) patients. The study group consisted of 46 consecutive motor complete (Frankel A or B) SCI patients admitted within 48 hours of injury. The ages of the patients ranged from 15 to 72 years. Neurologic levels ranged from C3 to T11. There were 19 high-level quadriplegic patients (HLQ; C3-C5), 11 low-level quadriplegic patients (LLQ; C6 C8), and 16 paraplegic patients (Para; T1-T11). The patients were followed during the first 30 days postinjury for radiographic evidence of A/P lasting more than three days. The time of onset, duration, and location of A/P was determined. Fifty percent (23 of 46) of the patients developed A/P in the first 30 days after their spinal cord injury. The incidence was higher in the HLQ than in the LLQ and Para (74% vs 33%; p less than 0.02 using the Fischer exact test). There was a preponderance (4:1 ratio) of left-sided involvement for A/P in this population (p = 0.01 using the two-tailed binomial test). Sixteen patients had left-sided A/P, four patients had right-sided A/P, and three patients had bilateral findings. There was no relationship between level of injury and side of involvement. The high incidence of left-sided pulmonary involvement in the acute SCI patient may be due to the tendency to retain secretions in this period combined with the increased difficulty of clearing secretions from the left lung. PMID- 2317138 TI - Functional neuromuscular stimulation for standing after spinal cord injury. AB - A study was undertaken to determine if functional neuromuscular stimulation could be used to obtain standing in patients with traumatic spinal cord injury. Twenty five subjects were selected during the study, and standing was accomplished in 21 using bilateral quadriceps stimulation with the hips in hyperextension. Four subjects elected not to continue participation to the point of standing. Stimulation parameters were 0 to 120V pulse amplitude, frequency 13Hz or 20Hz, and pulse width of 0.4msec. Confirmation of standing with support of 95% of the body weight by the legs was verified by quantitative measurements with a dual scale force platform or a biomechanics force platform. Subjects initially selected had injury levels between C7 and T11 and ranged in age from 22 to 47 years, with duration of injury from one to 13 years. The subjects had complete lesions, with no active motor function below the last normal level, and absent sensation or partial sparing of sensation with vague perception of pinprick, but no position sense. Six subjects stood at home and 15 stood only in the laboratory. This five-year experience indicates that paraplegic individuals may obtain standing with functional neuromuscular stimulation. PMID- 2317139 TI - Bone mineral density after bicycle ergometry training. AB - The effect of functional electrical stimulation (FES) cycle ergometry on bone mineral density (BMD) was investigated in six spinal cord injury (SCI) quadriplegic men. Each subject trained three days a week for six months on an FES cycle ergometer. Pretraining and posttraining BMD measurements of the proximal femur were performed using dual photon absorptiometry. Mean pretraining BMD (percent norm) for the femoral neck, Ward triangle, and trochanter were 66.65, 57.43, and 57.67, respectively. After six months of FES cycle ergometry, mean BMD measurements were 66.15, 57.07, and 55.13, respectively. There was no statistically significant difference between the pretraining and posttraining BMD measurements. All subjects were found to have osteoporotic proximal femurs when BMD was expressed as a percent of their age-matched controls. Bone mineral density measurements were subsequently performed on three additional men with SCI who had exercised for three years with the FES cycle ergometry modality. Their mean BMDs were not significantly different from the experimental group. This study demonstrated that six months of FES cycle ergometry did not produce an increase in BMD. PMID- 2317140 TI - Segmental H-reflex studies in upper and lower limbs of healthy subjects. AB - The H-reflex has been recorded from the flexor carpi radialis muscle in the upper limb and vastus medialis (quadriceps) muscle in the lower limb in relaxed healthy subjects. The characteristics of these reflexes have been compared with those of the soleus H-reflexes, recorded with the same technique, and similar behavior has been reported. The techniques and pitfalls of recording these segmental reflexes and their clinical and neurophysiologic significance are discussed in light of the relevant literature. These segmental reflexes will be useful in studying conduction and integrity of C7, L4, and S1 spinal segments. PMID- 2317141 TI - Anterior interosseous/median nerve latency ratio. AB - This report describes a new diagnostic technique for evaluating anterior interosseous nerve injuries (Kiloh Nevin syndrome). The resultant "AIM" (anterior interosseous/median nerve) score establishes a normal ratio of the pronator quadratus latency to the abductor pollicis brevis latency after one stimulus to the proximal median nerve and simultaneous recordings of the evoked response at the respective muscles. One hundred normal nerves were tested in 61 patients. The result was an AIM score of 0.60 (SD = 0.06). Five patients with Kiloh Nevin syndrome were evaluated. The average AIM score was 0.76 (SD = 0.04). Five patients with severe carpal tunnel syndrome were evaluated. The average AIM score was 0.38 (SD = 0.06). Ten patients with borderline carpal tunnel syndrome were evaluated. The average AIM score was 0.48 (SD = 0.06). Anterior interosseous nerve entrapment or compression injury remains a difficult clinical diagnosis because it is mainly a motor nerve and the syndrome is often mistaken for finger ligamentous injury. We describe an easily performed electrodiagnostic latency ratio technique to diagnose this injury. This technique may also be helpful as a screen for carpal tunnel syndrome when it is difficult to control for systemic illness. PMID- 2317142 TI - Physiologic and perceptual responses during treadmill running with ankle weights. AB - This study examined the effects of ankle weighting on physiologic and perceptual responses during treadmill running in seven healthy, female recreational runners with a mean maximal aerobic power of 48.4 +/- 4.0 ml/kg/min. Each subject completed four experimental one-mile runs at individually selected treadmill running speeds with 0, 1.6, 3.2 and 4.8 kg weights on their ankles. The subjects selected a speed at which they would run (train) if their objectives were to significantly improve cardiovascular function and induce weight loss. Metabolic and cardiovascular responses were continuously monitored, and ratings of perceived exertion were recorded near the end of the activity. During the unweighted run, the subjects selected a running speed of 6.87 +/- 0.63 mph which resulted in a net energy expenditure of 0.153 kcal/kg/min or 1.34 +/- 0.16 kcal/kg/mile. This corresponded to a training intensity of 76.3% +/- 5.1% of maximum oxygen consumption or 88.1% +/- 9.7% of maximum heart rate. Addition of weight to the ankles caused a significant decrease (p less than .05) in the running speed selected and, therefore, did not result in any significant changes (p greater than .05) in the rate of oxygen consumption, heart rate or ratings of perceived exertion when compared to the unweighted condition. These observations are in contrast to previous studies on ankle weighting which were conducted at fixed treadmill running speeds. However, the use of ankle weights did have a tendency to increase gross and net energy expenditure of running when values were expressed in kcal/mile because of slower self-selected running speeds under these conditions. This increase in energy expenditure could be of physiologic significance if running with ankle weights was performed on a regular basis at a fixed distance. PMID- 2317143 TI - Preoperative and postoperative gait evaluation in cerebral palsy. AB - The purpose of the study was to evaluate objectively and quantitatively the possible effects of surgical correction for equinus deformity on the gait of children with cerebral palsy (CP). Evaluation criteria selected were based on time and distance parameters of stride during gait. Ten children with confirmed diagnoses of CP took part in the study. They were tested before surgery and after surgery at four-month intervals for a period of up to one year. Results were compared to published data obtained on able-bodied, growing children to determine whether progress after the operation was faster than that expected in normal growth. Gait improvement was demonstrated by a decrease in support time and an increase in walking speed and stride length. Overall improvement was sometimes preceded by an initial, temporary deterioration. Results indicate that the time and distance parameters of stride can provide reliable objective evaluation of gait improvement after tendo Achilles lengthening in children with CP. PMID- 2317144 TI - Endurance training in the elderly nursing home patient. AB - Endurance training in nursing home patients was evaluated by selecting 15 of 150 patients for a conditioning program eliminating those patients with dementia and/or significant cardiac disease. After a medical and laboratory screen, all had a symptom-limited exercise test (SLXT) using arm and leg ergometry. Only two patients were able to use the treadmill and many had difficulty with leg cycling. Exercise capacities averaged 2-3METs in most patients. The exercise (E) group included eight randomly selected subjects who participated in a three times weekly upper and lower conditioning program using target heart rates based on the SLXT. The control (C) group continued in the daily nursing home routine. The SLXT was repeated at the end of one year. Two patients in each group expired from unassociated medical problems. Three patients in group E were hospitalized for brief periods. In group E there was a small but significant training effect in the arms (p = 0.05) but not in the legs. It would appear that a small training effect can occur in elderly nursing home patients with a conditioning program. The magnitude is limited by the low intensity of the program as well as the detraining effect of intercurrent illness. Functional limitations of the legs may be responsible for the lack of a training effect in these muscle groups. PMID- 2317145 TI - Guillain-Barre syndrome in children: evidence of axonal degeneration and long term follow-up. AB - A retrospective study was done of 12 children who met the NINCDS clinical criteria for the diagnosis of Guillain-Barre syndrome and who were hospitalized with this diagnosis. Electrodiagnostic testing was sufficiently complete for interpretation of the neuropathophysiology in six children. Long-term outcome was determined through examination by a physician one to eight years after onset in all six children, and was supplemented by telephone follow-up with the children or their parents by the authors five to eight years after onset. Long-term clinical outcome was analyzed for any correlation between poor outcome and axonal degeneration. The electrodiagnostic tests were consistent with primarily axonal neuropathophysiology in three of the six children. Poor clinical outcome appeared to correlate with electrodiagnostic evidence of primarily axonal pathophysiology, or absence of an evoked M-response, or both. PMID- 2317146 TI - Overwork weakness with evidence of muscle damage in a patient with residual paralysis from polio. AB - Overwork weakness has been reported in survivors of poliomyelitis with residual paralysis. Investigators have recently reported that approximately 25% of polio survivors experience functional declines with onset of symptoms of new weakness, fatigue, and muscle pain. The diagnosis of overwork weakness has remained a clinical diagnosis, as previous investigations have failed to uncover reliable, objective, diagnostic methods to confirm the diagnosis in symptomatic individuals. A case is presented in which markedly elevated levels of CPK were present with symptoms of weakness, fatigue, and muscle pain. These levels declined after clinical intervention, with resolution of symptoms. This case represents an overuse syndrome in which muscle fibers were being damaged through overuse. This case further suggests the possible role of serum CPK in the diagnosis of, and in monitoring clinical intervention in, some polio survivors who experience overwork weakness. PMID- 2317147 TI - Isolated lesion of the lateral cutaneous nerve of the forearm. AB - Because of its location in the antecubital fossa, the lateral cutaneous nerve of the forearm is at risk of injury when a person is carrying objects with the forearm flexed or during venipuncture. Injury to this nerve, however, is rarely reported. A case report of traumatic injury to the lateral cutaneous nerve, the use of appropriate nerve conduction studies for diagnosis, and a discussion of the available literature is presented. PMID- 2317148 TI - Acute pulmonary edema following removal of a spinal orthosis: an unusual complication of a halo vest. AB - The halo vest is a commonly used spinal orthosis that provides stability to the cervical spine. Known complications include loss of spinal reduction, local pin tract infection, skin breakdown over the scapulae, and, rarely, brachial plexus and cranial nerve palsies. The use of the halo vest has not been associated with significant respiratory compromise. Cardiopulmonary complications associated with halo vests have not been reported. We report a case of pulmonary edema associated with removal of a halo vest in a patient with occult mitral stenosis. We speculate that removal of the orthosis resulted in rapid redistribution of peripheral blood volume sufficient in magnitude to provide the hemodynamic substrate for acute pulmonary edema. PMID- 2317149 TI - Familial fibromyalgia and/or myofascial pain syndrome? PMID- 2317150 TI - Isokinetic testing. PMID- 2317151 TI - Studies in the in vivo expression of the influenza resistance gene Mx by in-situ hybridisation. AB - The inbred laboratory mouse strain A2G carries a functional, interferon type 1 inducible gene, Mx which upon expression confers specific resistance to an otherwise lethal dose of influenza virus. We investigated in vivo Mx gene expression by performing Northern hybridisation and in-situ hybridisation on A2G (Mx+) and (CBA/J x C57)F1 (Mx-) mice that were induced either with human, natural interferon; human, recombinant interferon or double stranded poly(I):(C). All 3 inducers were able to stimulate Mx expression in all organs examined in the A2G strain. However, contrary to previous reports, Mx expression was confined to a small number of cell types; the main contributor was most probably mononuclear cells. Specialised cells such as hepatocyte, nephron, ovarian follicle and seminiferous tubules did not show detectable Mx level. There was also constitutive Mx expression in the epithelia of uterus and duodenum which suggested direct gene activation independent of blood-bourne interferon. PMID- 2317152 TI - The cleavage of p62, the precursor of E2 and E3, is an early and continuous event in Semliki Forest virus-infected Aedes albopictus cells. AB - The cleavage of p62 of Semliki Forest virus (SFV) in C6/36 (Aedes albopictus) cells was investigated by pulse-chase labeling experiments and analysis of the sugar side chain of E1 using endoglycosidases. Similar to vertebrates, E1, E2, and p62 are transported as complexes in C6/36 cells. This observation allows the use of E1 as a positional marker for the transport and processing of E2 and p62. The oligosaccharide on the viral spike E1 protein was modified first to an Endo-D sensitive (35 min) and then to an Endo-H-resistant structure (55 min), whereas the oligosaccharides of p62 remained sensitive towards Endo-H the whole time. E2 could be detected already at 10-20 min post synthesis, suggesting that p62 cleavage starts early, probably before the protein has been transported to the Golgi apparatus. This is in contrast to the cleavage taking place later mainly near the plasma membrane of higher eukaryotes. The spike proteins finally appeared in extracellular virions after about 70-90 min post synthesis. PMID- 2317153 TI - Adenovirus 41 growth in semi-permissive cells shows multiple-hit kinetics. AB - Adenovirus type 41 infection of semi-permissive Chang conjunctival cells, monitored by fluorescent focus assay, followed multiple-hit kinetics. In non permissive human cells, type 41 showed infectivity with two-hit kinetics in the presence of type 2. Type 41 infectivity was seen to be directly proportional to input concentration (one-hit) only in 293 cells, a continuous human line expressing Ad 5 E1 products. PMID- 2317154 TI - Host-range modifications of bacteriophage epsilon 15. AB - Host-range modifications were observed after multiplication of bacteriophage epsilon 15 on Salmonella strains belonging to five serovars. The phage preparations obtained were tested at RTD (routine test dilution) on strains belonging to the same serovars. In each serovar, three kinds of reaction patterns were observed: (a) specific sensitivity only to the phage multiplied on the same serovar; (b) sensitivity to all host-range modifications of the phage; (c) lack of sensitivity to all phage preparations, at RTD. PMID- 2317155 TI - Induction of interleukin-1 alpha and beta gene transcription in mouse peritoneal exudate cells after intraperitoneal infection with herpes simplex virus-1. AB - Macrophages have been shown to play a determining role in the immune defense against herpes simplex virus-1 (HIV-1) intraperitoneal infection in the mouse. In the present study, the effect of HSV-1 infection on interleukin-1 alpha and beta gene transcription in peritoneal exudate cells was investigated. HSV-1 infection was found to induce interleukin-1 alpha and beta gene transcription in these cells. Induction of the interleukin-1 beta gene initiated 6 h postinfection (p.i.) and terminated at 48 h p.i. In contrast, interleukin-1 alpha RNA was detectable at high levels at 6h p.i. but not at 24 h p.i. Inactivation of virus prior to infection prevented HSV-1-induced IL-1 gene induction, indicating that only infectious virus is able to stimulate IL-1 gene transcription. These findings are discussed in relation to the role of macrophages in the immunological mechanisms of defense against HSV-1 infection. PMID- 2317156 TI - Atherogenesis during low level hypercholesterolemia in the nonhuman primate. II. Fatty streak conversion to fibrous plaque. AB - This study focuses on the formation of lesions of atherosclerosis in the aortas and iliac arteries of nonhuman primates (Macaca nemestrina) maintained on a low level hypercholesterolemic diet (plasma cholesterol 200 to 400 mg/dl) for 2, 3, or 3.5 years. Advanced lesions, or fibrous plaques, were found in all of the animals. The extent and severity of the lesions were closely related to the level and duration of hypercholesterolemia. The presence of monocyte-macrophages, T lymphocytes, and smooth muscle cells, and the interactions of those cells that precede fibrous plaque formation in these long-term, relatively low level hypercholesterolemic monkeys were similar to those observed in previously published studies of high level hypercholesterolemia in nonhuman primates, with one principal difference: the fibrous plaques in the longer-term, low level hypercholesterolemic animals contained increased amounts of fibrous connective tissue, more smooth muscle cells, and fewer macrophages. As in the studies with high levels of hypercholesterolemia, fibrous plaques were more frequently observed in the abdominal aorta and iliac arteries than in the thoracic aorta and aortic arch. Fibrous plaques were preferentially located at the branches and bifurcations of the arteries. These anatomic sites were consistent with those that contained fatty streaks and fibrofatty lesions in the animals fed the diet for shorter periods of time. These data are compatible with the proposal that many of the fatty streaks are converted to fibrofatty lesions, some of which ultimately become converted to fibrous plaques. PMID- 2317157 TI - Uremic levels of oxalic acid suppress replication and migration of human endothelial cells. AB - Patients with chronic renal failure who undergo hemodialysis experience accelerated atherosclerosis and premature death. Since the end-metabolite, oxalic acid, accumulates in plasma in proportion to the severity of renal failure, we studied whether sodium oxalate (0 to 300 microM) is an endothelial toxin and, therefore, might enhance atherogenesis. Exposure to uremic levels of oxalate (greater than 30 microM) for 9 to 28 days depressed endothelial cell replication by 33% to 84% (mean +/- SD, 54% +/- 15.7%, n = 17 experiments, p = 0.002). In contrast, replication of fibroblasts exposed to 200 microM oxalate for 45 days was not inhibited. The inhibitory effect of oxalate on endothelial cell replication was both dose- and time-dependent (both p less than 0.0001) and was first detected 3 to 7 days after the initial exposure to oxalate. Further, the inhibitory effect was fully reversible upon removal of oxalate, but only if exposure was limited to 5 days or less. Sodium salts of other carboxylic acids (citric, succinic, glyoxylic, and malonic; 200 microM) as well as HCl (200 microM) did not suppress endothelial cell replication. Oxalate also inhibited endothelial cell migration but had no effect on basal, thrombin-induced, or arachidonate-induced prostacyclin production by endothelial cells. Exposure of endothelial cells to sodium oxalate (200 microM) for as little as 24 hours-a time period sufficient to induce delayed, transient inhibition of replication not detectable until approximately 1 week after exposure-inhibited incorporation of 3H-leucine into protein by 40% (p = 0.009). We conclude that sodium oxalate acts as a uremic toxin, inhibiting endothelial cell replication and migration, functions which may be important for constitutive inhibition of atherosclerosis. PMID- 2317158 TI - Expression of elastase activity by human monocyte-macrophages is modulated by cellular cholesterol content, inflammatory mediators, and phorbol myristate acetate. AB - We investigated the effects of a number of stimulatory agents on the production of both cell-associated and extracellular elastase-type enzymes on human monocyte macrophages in vitro and of the modulation of such effects by modification of cellular cholesterol content. The stimulatory agents included phorbol myristate acetate (PMA) and the inflammatory mediators, lipopolysaccharide (LPS), opsonized zymosan (OZ), and platelet activating factor (PAF). Using the synthetic substrate, N-succinyl-trialanyl-paranitroanilide (SANA), we detected cell associated elastase-like activity in monocyte-derived macrophages. Such activity increased markedly with cell maturation over the period from 5 to 15 days of adherence culture. While PAF (10 micrograms/ml) and LPS (10 micrograms/ml) were without effect on cell-associated elastase-like activity in macrophages, PMA (100 ng/ml) and OZ (1 mg/ml) markedly stimulated such activity in cells cultured for 15 days. Furthermore, a fivefold increase in the cell-associated elastase-like activity of macrophages occurred upon cholesterol loading of the cells with acetylated low density lipoprotein (AcLDL). By contrast, this activity was markedly diminished upon depletion of cellular cholesterol content after incubation with high density lipoprotein (HDL3). Latent elastinolytic activity in the culture medium was detected by use of a radioactive substrate, insoluble 3H elastin, after initial tryptic treatment of the medium. Such latent elastase activity was secreted only by activated macrophages; the relative potency of stimulation was: PMA greater than LPS = PAF greater than OZ. Increase in cellular cholesterol content alone markedly enhanced the secretion of elastase (from undetectable levels to 28 ng of 3H-elastin degraded/hr/micrograms DNA). In all cases, both the cell-associated and secreted latent elastinolytic activities were due to metalloproteases, in view of their 90% inhibition by 2 mM EDTA. Cholesterol-loaded macrophages, which displayed an approximately 40-fold increase in total cholesterol content as compared to control cells, remained sensitive to the action of activators of OZ and PMA, while LPS and PAF exerted only weak effects. Our data indicate that cellular cholesterol content and inflammatory mediators are effective stimulants of the production and secretion of elastase type enzymes by human monocyte-macrophages. Among these factors, cellular cholesterol content, OZ, PAF, and LPS may represent factors of relevance to the inflammatory role of the macrophage in atherogenesis and more specifically to the alteration of elastin structure in the extracellular matrix of the vessel wall. PMID- 2317159 TI - Noninvasive imaging of 99mtechnetium-labeled low density lipoprotein uptake by tendon xanthomas in hypercholesterolemic patients. AB - Technetium-labeled low density lipoproteins (Tc-LDL) appear to be useful for describing LDL biodistribution in normal and dyslipidemic subjects. We injected 99mTc-LDL into subjects with large tendon xanthomas secondary to homozygous familial hypercholesterolemia or sitosterolemia. Rapid (4 hours) accumulation of Tc-99m activity in xanthomas was observed, and this accumulation increased over a 24-hour period. No comparable accumulations of Tc-99m activity were noted in normal subjects or in a subject with heterozygous familial hypercholesterolemia who had very small tendon xanthomas. These findings support previous biopsy data indicating active uptake of LDL by macrophages within xanthoma and suggest that 99mTc-LDL imaging of xanthomas may be useful in studies of the effects of diet and drugs on the accumulation of lipoproteins by atherosclerotic plaques. PMID- 2317160 TI - Fate of fibrinogen in human arterial intima. AB - Fibrinogen and fibrinogen/fibrin-related antigen (total FRA) was measured in human normal intima and different types of atherosclerotic lesions and mural thrombi. The amount showed marked variation between groups of tissue samples, but within each group there was a significant correlation between levels of total FRA and low density lipoprotein (LDL), suggesting that some common factor must influence their influx or retention. The total FRA were analyzed by gradient sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting with antisera to whole fibrinogen and fragments D and E, and fibrinopeptide A (FPA). All intimal samples (but not thrombi) contained fragment X, the first product of plasmin digestion of fibrinogen, but fragment Y was present in only half the samples, and no core-fragment E containing FPA was detected in any sample, suggesting that fibrinogenolysis is limited. By contrast, all samples contained fragment E, which was negative for FPA, so presumably derived from fibrin; they also contained fragments D-dimer and DY, which are characteristic degradation products of cross-linked fibrin. There were no differences between samples obtained during reconstructive vascular surgery and samples obtained at autopsy, so the patterns appear to represent the steady state. This implies that within the intima there is continuous formation of cross-linked fibrin and continuous fibrinolysis, both processes generating fragments that may have atherogenic properties. PMID- 2317161 TI - Collagen type III induced ex vivo thrombogenesis in humans. Role of platelets and leukocytes in deposition of fibrin. AB - Exposure of type III collagen coats on plastic cover slips in parallel-plate perfusion chambers to flowing nonanticoagulated human blood resulted in deposition of platelets and fibrin. Blood was drawn directly from an antecubital vein by an occlusive roller pump over the collagen coats in chambers having flow slits of different dimensions, so that wall shear rates of 100, 650, and 2600 s-1 were obtained at 10 ml/min. Coagulation was minimally activated during the passage of blood from the vein to the chamber as shown by fibrinopeptide A levels of 3.7 ng/ml after 5-minute perfusions. The surface coverage with platelets increased from 18% at 100 s-1 to 59% at 2600 s-1, and the corresponding thrombus volumes increased from 2 to 22 microns 3/microns 2, respectively. This contrasted with the coverage with fibrin on collagen, which decreased from 28% at 100 s-1 to 9% at 2600 s-1. Fibrin deposits on the thrombi covered 6% of the surface irrespective of the shear rate, indicating that some of the deposited platelets accelerated the deposition of fibrin. The type III collagen preparation did not activate factor XII and did not possess tissue factor activity, indicating that the surface itself was not procoagulant. However, a correlation between deposited leukocytes and surface coverage with fibrin was observed (r = 0.78, p less than 0.01), suggesting a role for these cells in the deposition of fibrin. The data demonstrate that thrombogenesis is triggered by pure type III collagen, although the deposition of fibrin is not initiated by the collagen itself but presumably by deposited leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317162 TI - Apolipoprotein E4 homozygosity predisposes to serum cholesterol elevation during high fat diet. AB - The hypothesis that apolipoprotein E (apo E)-isoform-related differences in plasma and LDL cholesterol concentrations are due to differential responses to dietary lipids was explored in 110 North Karelian subjects who had previously participated in dietary intervention studies. This was accomplished by collecting fresh blood samples for apo E phenotyping and by re-analysis of the original plasma lipid data according to apo E phenotypes. During high fat, high cholesterol baseline (p = 0.003) and switchback diets (p = 0.002), plasma cholesterol correlated inversely with the sum of subscript numbers (e.g., apo E3/4 = 7). Thus, subjects with the apo E4/4 phenotype had the highest (7.63 +/- 1.32 mmol/l), and subjects with the apo E3/2 phenotype had the lowest baseline levels of plasma cholesterol (5.85 +/- 1.48 mmol/l). This association became weaker during a low fat, low cholesterol diet intervention (p = 0.069). Greater reductions in plasma cholesterol occurred in subjects homozygous for the apo epsilon 4 allele (-1.84 mmol/l) as compared to subjects with other genotypes ( 1.13 mmol/l) (p = 0.0097). Moreover, these subjects responded to the switchback diet by greater increases in plasma cholesterol (1.52 mmol/l) than others (0.92 mmol/l, p = 0.0141). The results suggest that the effect of apo epsilon genotype on plasma cholesterol is modulated by dietary fat and cholesterol intake. PMID- 2317164 TI - Proliferation of smooth muscle cells at sites distant from vascular injury. AB - This study investigated the phenomenon that injury at one specific site in blood vessels induces cell replication at distant vascular sites. A polyethylene tube was inserted via the common carotid into rat aortic arch, which caused focal endothelial cell loss and formation of platelet thrombi. In a similar fashion, a polyethylene tube was placed into the lower abdominal aorta via a femoral artery. All animals received 3H-thymidine continuously for 2 weeks, after which time segments of the aorta distant from the polyethylene tubing were processed for autoradiography. These sites showed no loss of endothelium or adherent platelets, and yet the smooth muscle and endothelial cell replications were significantly elevated as compared to control aortas. There was no significant change in blood pressure during these experiments and no increase in smooth muscle cell ploidy. When the polyethylene tubing was left in situ for 2 months, no increased replication of the smooth muscle cells was observed during the last 2 weeks of the experiment, and at this time the aorta adjacent to the tubing was completely re-endothelialized. Finally, the mitogenic activity of plasma from these animals was tested in vitro. At the time of a significant increase of in vivo cell replication (2 weeks), the mitogenic activity of the plasma from animals with the indwelling tubing was similar to that of the control animals. In summary, these data show that injury at one discrete arterial site leads to general cell proliferation in the same vessel, and the data would support the possibility that cell communication initiates this response. PMID- 2317163 TI - Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin. AB - We examined the relationship between cholesterol synthesis and high affinity low density lipoprotein (LDL) catabolism in freshly isolated mononuclear leukocytes and plasma sterols and apolipoprotein concentrations in three homozygous and one heterozygous subject with sitosterolemia with xanthomatosis and in 12 control subjects. Observations in untreated subjects were compared during therapy with lovastatin or interruption of the enterohepatic circulation of bile acids. Plasma cholesterol, plant sterol, and apolipoprotein B concentrations declined more than 50% in the two homozygous sitosterolemic subjects after ileal bypass surgery. In contrast, plasma cholesterol, plant sterol, and apolipoprotein B concentrations remained constant in a homozygous sitosterolemic subject and declined only 7% in a heterozygous sitosterolemic subject during 20 weeks of lovastatin (40 mg/day) treatment compared to a 28% decrease in similarly treated control subjects. Lovastatin treatment decreased cholesterol synthesis more than 60% but did not increase high affinity catabolism of LDL further in the sitosterolemic cells, compared to a more than 20% rise in control mononuclear leukocytes. Conversely, bile acid malabsorption increased cholesterol synthesis 59%, total hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity 13%, and receptor mediated LDL degradation 41% in control cells, but did not stimulate cholesterol synthesis or microsomal HMG-CoA reductase activity in sitosterolemic mononuclear leukocytes although receptor-mediated LDL catabolism rose an additional 26%. These results demonstrate a greater than expected decrease in plasma sterols and apolipoprotein B concentrations in sitosterolemic subjects after stimulation of bile acid synthesis because of the inability to up-regulate cholesterol production. We suggest that bile acid-sequestering drugs or ileal exclusion surgery may be more effective treatments to mobilize accumulated sterol deposits and prevent atherosclerosis in this disease. PMID- 2317165 TI - Dynamic monitoring of platelet deposition on severely damaged vessel wall in flowing blood. Effects of different stenoses on thrombus growth. AB - The formation of an arterial thrombus is a dynamic process that depends upon the characteristics of blood flow, the triggering substrate, and the blood components. We have developed and characterized a sensitive and specific computer assisted nuclear scintigraphic method to study the dynamics of platelet deposition on severely damaged vessels both in vitro and in vivo in nonstenotic and stenotic flow conditions. Heparinized pig blood with Indium-111-labeled platelets was perfused for 50 minutes. Method variability in both static and flowing conditions was evaluated by Indium-111-labeled transferrin and Indium-111 labeled platelets. Positive scintigrams were obtained mainly in the presence of severe high grade stenoses on a thrombogenic substrate. Since the method is highly sensitive, computer-assisted axial dependence analysis was performed on the scintigraphic images to locate the thrombotic accumulation with respect to the area of the stenosis and to monitor the dynamic changes in platelet accumulation over time. Both in vitro and in vivo the highest level of platelet deposition occurred at the apex of the 80% stenosis, where embolization could be usually detected after 30 minutes of perfusion. This study is the first to assess the dynamics of thrombus growth in nonparallel flow streamlines such as are encountered in stenotic vessels. This method provides a new experimental tool with which to study factors affecting thrombus formation and stability. PMID- 2317166 TI - Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice. AB - Female mice of 16 inbred mouse strains were fed an atherogenic diet for 14 weeks and were then evaluated for atherosclerotic lesions in the aorta. Strains C57BL/6, C57BR/cd, C57L, and SM were very susceptible to atherosclerosis, with lesion area/aortic cross-sections in the range of 4500 to 8000 microns 2. Strains C58 and SWR were intermediate in susceptibility, with lesion area/sections in the range of 1670 to 1690 microns 2. Strains 129, AKR, DBA/2, and BALB/c had only small lesions in the range of 20 to 350 microns 2/section; strains C3H, NZB, CBA, HRS, SJL, and A had no lesions after 14 weeks. Lesion formation in five strains was compared at several time points. Strain C57BL/6 mice developed lesions by 7 weeks, and these continued to grow until all mice had large atheromatous plaques in the aorta and coronary arteries. Strains AKR and DBA/2 also had fatty streak lesions as early as 7 or 8 weeks, but these lesions had not progressed in size by 14 weeks. Strains BALB/c and C3H, which were both resistant to lesion formation at 14 weeks, diverged from each other as time progressed. By 1 year, BALB/c mice had large lesions, but C3H mice had none. Most of the inbred strains chosen for evaluation are the progenitors of recombinant inbred sets of strains, a genetic tool that greatly facilitates the analysis of strain differences. This survey indicates seven additional recombinant inbred sets of strains whose progenitors differ in atherosclerosis susceptibility: BXD, AKXL, SWXJ, NX8, 129XB, NXSM, and B6NXAKRN. An analysis of these recombinant inbred strains may reveal additional mouse genes affecting atherosclerosis susceptibility. PMID- 2317168 TI - AIDS open line. PMID- 2317169 TI - The expert witness. PMID- 2317167 TI - Award restructuring. PMID- 2317170 TI - A practical guide to duty of care. PMID- 2317171 TI - The fluoroquinolone antibacterial agents. PMID- 2317172 TI - An historical perspective on registration. PMID- 2317173 TI - Influence of 7 days of hindlimb suspension and intermittent weight support on rat muscle mechanical properties. AB - Unloading the rat hindlimb results in a decrease in mass, especially in those muscles that normally have a load-bearing function. The present study was designed to evaluate the effect of intermittent periods of weight support in ameliorating this atrophic response. Adult male Sprague-Dawley rats were assigned to either a control (CON), a hindlimb suspended (HS), or a hindlimb suspended plus intermittent weight support (HS-WS) group. HS-WS rats were walked slowly on a treadmill at 0.2 m/s and a 19% incline for 10 min, every 6 h. After 7 d, the in situ mechanical properties of the soleus (Sol) and medial gastrocnemius (MG) were studied. Body weights of HS and HS-WS rats were 9 and 13% lower than CON. The SOl weight relative to body weight was 21 and 9% lower in HS and HS-WS than CON. Maximum tetanic tension relative to muscle mass was significantly lower in HS than CON, whereas HS-WS had values similar to CON. The MG weight relative to body weight was significantly lower in both suspended groups. The maximum tetanic tension relative to muscle weight was significantly elevated in HS-WS compared to CON, suggesting that weight support may have preferentially maintained the contractile protein component of the muscle. Contraction times were 25% faster (p less than 0.05) in the Sol and unchanged in teh MG of HS rats. For each muscle, the fatigue properties were similar in all groups. These data indicate that a low force, short-duration exercise regime results in a significant functional recovery in the "slow" Sol, whereas the "fast" MG is less affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317174 TI - Effects of whole-body vibration waveform and display collimation on the performance of a complex manual control task. AB - An experiment is described in which two independent groups of eight subjects each performed a combined continuous and discrete tracking task during exposure to vertical whole-body vibration. Both groups received sinusoidal and random vibration at preferred third-octave centre frequencies of 0.5-10 Hz. One group performed the task with the display collimated by a convex lens. Without the collimation, performance was disrupted by both types of vibration at all vibration frequencies; collimation removed the disruption at frequencies above 1.6 Hz. There were differences in the effects of random and sinusoidal vibration at 2.0 and 2.5 Hz, suggesting that compensatory eye movements were assisting performance during exposure to the predictable sinusoidal motion. The results show that continuous control performance was disrupted by visual interference at frequencies above 1.6 Hz; closed-loop system transfer functions showed that visual interference increased the phase lags which impaired control performance. Possible mechanisms explaining the disruption in performance at lower frequencies are discussed. PMID- 2317175 TI - Human temperature regulation during exercise after oral pyridostigmine administration. AB - Four healthy males exercised in two experiments at ambient temperatures of 22, 29, and 36 degrees C with the relative humidity at 30% in all environments (Tdp = 3.9, 9.9, and 15.8 degrees C). One experiment in each environment was done 150 min after 30 mg oral pyridostigmine bromide (PYR) administration, and the second experiment was done on a separate day with no medication (CON). Red blood cell cholinesterase was 39 +/- 7% lower after PYR (11.8 vs 7.2 micromol.ml-1.min-1). Esophageal (Tes) and mean skin temperature (Tsk), forearm blood flow (FBF), forearm sweating, and skin blood flow (SkBF) were measured twice each minute during a 15-min rest period and during 30-min of seated cycle exercise at approximately 58% Vo2peak. Whole body sweating was determined from weight changes before and after exercise. PYR decreased heart rate at rest and during exercise at 29 degrees C and 36 degrees C (8bpm, p less than 0.05). Resting SkBF was 40% lower at 29 degrees C and 30% lower at 36 degrees C after PYR compared to CON (p less than 0.05). There was no effect of PYR on heat production at rest or during exercise. Tsk was different in the three conditions by design, but was unchanged by PYR. Tes was not different at rest in any condition, but was elevated during exercise at 36 degrees C (0.1 degree C, p less than 0.05) in PYR compared to CON. These data suggest that pyridostigmine ingestion decreased skin blood flow, which may limit exercise thermoregulation in more severe environments. PMID- 2317176 TI - Altitude symptomatology and mood states during a climb to 3,630 meters. AB - Ascents to altitudes above 3,050 m have been shown to cause adverse changes in symptoms and moods. The severity of these changes may depend not only on the altitude and rate of climb, but also on the length of stay and the effort expended to reach the desired altitude. In order to better understand how these factors influence symptom and mood changes during a climb, this study systematically assessed symptoms and moods during an ascent to 3,630 m. Self rated symptoms and moods were determined in seven male volunteers over a period of 7 days (d) during a climb to 3,630 m of Mount Sanford, AK. The subjects were tested five times--twice at 2,225 m, then at 2,530, 3,080, and 3,630 m. Symptoms and moods were assessed with the Environmental Symptoms Questionnaire (ESQ) and the Profile of Mood States (POMS), respectively. Seven symptom factors and two mood factors were found to be adversely affected over time by the changes in altitude. More specifically, the subjects experienced more respiratory acute mountain sickness (AMS), exertion stress, and muscular discomfort and they were also colder, less alert, less vigorous, and more fatigued at higher elevations. These changes occurred primarily at 3,630 m and most also occurred at 3,080 m.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317178 TI - Effect of hypoxia on VO2 kinetics during pseudorandom binary sequence exercise. AB - The dynamic response characteristics of the oxygen uptake (VO2) response were investigated during upright cycle ergometer exercise in six healthy male volunteers. The exercise test consisted of a pseudorandom binary sequence (PRBS) with 15 units per sequence, each unit 15 s long, for a total period of 225 s. Six identical sequences were completed in a single test session. Each subject exercised under both normoxic and hypoxic (FIO2 = 14%) conditions. VO2 was measured breath-by-breath. The data were analyzed in the frequency domain by Fourier analysis to yield amplitude and phase shift coefficients for the relationship between the input work rate and the output responses of VO2 and heart rate (HR). The amplitude of the VO2/work rate was significantly reduced by hypoxia compared to normoxia over a wide range of frequencies. The mean VO2 was not different between hypoxia and normoxia. The phase shift for the VO2/work rate response was significantly greater for hypoxia than normoxia. The amplitude of the HR/work rate relationship was not significantly altered by hypoxia; however, the mean HR was higher during hypoxia. The phase shift of the HR/work rate response was significantly different between hypoxia and normoxia only at certain frequencies. These data indicate that the effects of hypoxia on the cardiorespiratory response to exercise can be characterized by the use of PRBS exercise and Fourier analysis techniques. A significant reduction in the ability of the cardiorespiratory system to adapt to changes in work rate appears to be caused by a reduction in the arterial O2 content. PMID- 2317177 TI - Periodic breathing and O2 saturation in relation to sleep stages at high altitude. AB - This study was designed to compare sleep organization at high altitude (HA) and sea level (SL) and to estimate the extent periodic breathing (PB) negatively influences arterial O2 saturation (SaO2). Six lowlanders were studied at SL and after 3 weeks spent at 3,800 m (La Paz, Bolivia). Three EEG leads, EOG, submental EMG, chest and abdominal motion, temperature of ventilated gas, and SaO2 were polygraphically recorded. Comparison of HA and SL data disclosed that: 1) Sleep organization was identical, with the same percentage of REM and stage 4. 2) PB (cycle length: 20 s; central apnea: 9 s) occurred in three subjects during all stages of sleep except REM (43-60% of total sleep). A periodic lowering in heart rate occurred during ventilatory oscillation. 3) During PB, SaO2 oscillated very regularly from 78-90%, which resulted in a mean SaO2 value calculated during oscillations similar to that of the non-periodic breathers. We conclude that lung O2 uptake during PB is preserved. PMID- 2317179 TI - Cardiovascular response to 4 hours of 6 degrees head-down tilt or of 30 degrees head-up tilt bed rest. AB - The cardiovascular responses to 4 h of 6 degrees head-down tilt (HDT) were compared to those of 4 h of 30 degrees head-up tilt (HUT) following a period of 1 h baseline in the 30 degrees HUT position. Eight healthy males completed each tilt position. Immediately on assuming HDT, heart rate decreased slightly from baseline, but did not differ from HUT. Stroke volume and cardiac output both increased significantly by as much as 54% and 26%, respectively, in the first minute of HDT. The difference between HDT and HUT was no longer present after 30 min. Mean arterial blood pressure was unchanged throughout 4 h or HUT or HDT. The ratio of pre-injection period to left ventricular ejection time was significantly decreased across all 4 h of HDT. Plasma volume was slightly elevated over the 4 h of HDT, while plasma hemoglobin concentration was significantly reduced. No evidence of a diuresis was found with 4 h HDT. Plasma catecholamines were not different between HDT and HUT. The present results show that the immediate transition from a HUT to a HDT position causes a dramatic change in cardiovascular variables. These changes are generally transient with baseline values resumed by many variables within 30 min of exposure to 6 degrees HDT. PMID- 2317180 TI - The use of tympanometry to detect aerotitis media in hypobaric chamber operations. AB - Diagnosis and quantification of aerotitis media were performed using a modified commercially-available tympanometer under hypobaric conditions. Subjects were 22 males and 9 females, 22-43 years of age, who were tested in each ear with the tympanometer prior to and after exposure, sequentially at the barometric pressure plateaus of 706, 656, 609, 586, 564, and 522 mm Hg, and following an induced ear block during a 1-min descent from 522 to 586 mm Hg. Each subject was examined once either alone or in pairs during a 90-min exposure. Aerotitis media was detected using tympanometry at simulated altitude as evidenced by the difference between measurements made during induced ear blocks and those made prior to inducement, as well as following relief of the pressure differential with the Valsalva maneuver. There were no significant differences between pre- and post induced aerotitis media values at 586 mm Hg, or between pre- and post-hypobaria. Our study suggests that tympanometry can be a valuable tool in managing aerotitis media in the aeromedical environment. PMID- 2317181 TI - Clinical aspects of inflight incapacitations in commercial aviation. AB - Sudden incapacitations can affect a pilot and even a whole crew during a flight, preventing them from performing their task in complete safety. In some cases, they could even cause an accident. Our study examines the causes of sudden in flight incapacitation in Air France pilots and flight engineers from 1968-88. Ten cases were reported out of a population of 1,800 cockpit crew, each flying an average of 600 h/year. These incapacitations were due to cardiac disorders (1 atrial fibrillation, 1 sinus tachycardia), epileptic attacks (2 generalized seizures), duodenal hemorrhages (2 cases), infection (1 case of severe vertigo due to viral labyrinthitis), metabolic disorders (1 case of hypoglycemia), and sometimes disorders affecting the whole crew (1 case of hypoxia due to a pressurization deficiency, 1 case of CO2 intoxication caused by the inadequate packaging of a container refrigerated in dry ice). Seven times out of ten, incapacitations occurred during cruising, twice during approach, and once on the ground before starting up, with closed doors (CO2 intoxication). Two of these incapacitations led to flight diversions. None of them caused an accident. In this series, incapacitations of a cardiac nature were rarer and less serious than those caused by gastrointestinal or neurological disorders. Prevention is based on detection during systematic medical check-ups, and on crews being trained to recognize subtle incapacitations early and to ensure that the flight continues safely when such a case occurs. PMID- 2317182 TI - An analysis of factors impeding passenger escape from aircraft fires. AB - The aviation world has long recognised that fires in aircraft are potentially very dangerous, being the cause of considerable mortality and morbidity even in otherwise survivable accidents. The evidence accumulated in the British Airtours Boeing 737 accident at Manchester International Airport on 22 August 1985, and the information acquired as a result of this investigation, reinforce the long held view that protection for passengers is needed. Heat, smoke, and toxic fumes can incapacitate people very rapidly. The time it took for people to die cannot be accurately assessed, but it is likely that all died within 4.5 min of the emergency being declared and probably within 2 min of smoke and flames entering the fuselage. Thus, it is obvious that new measures will have to be taken if lives are to be saved in future events of this nature. PMID- 2317183 TI - Voice analysis to predict the psychological or physical state of a speaker. AB - A vocal message, apart from its semantic content, carries information on the psychological and physiological condition of the speaker. Physical fatigue and especially psychological stress are the pathological elements of the condition. The accepted term for the cause of these effects is the "workload." This article describes the main research carried out since the 1940's to measure the acoustic modifications of the voice brought about by a workload. It concludes by a critical analysis of the studies and a short description of the perspectives for research. Their results mainly concern astronauts and pilots involved in specific high-stress tasks and possible users of voice recognition systems. All the studies show an excellent approach to this field of research but deserve to be widened, deepened, and made more accurate to enable estimating the nature or level of reaction to a workload. PMID- 2317184 TI - [The suitability of morphometric parameters of fat cell size for the purposes of animal science research. 1. Cellularity of swine subcutaneous adipose tissue influenced by different fattening ages and graded feed levels]. AB - The cellularity of subcutaneous adipose tissue of 108 male castrated pigs (German Landrace) was investigated. The tissue was taken bioptically under anesthetic conditions. The outer and the inner layer of backfat were examined separately, fresh unfixed tissue slices floating in Ringer solution were subjected to microscopic measurements of adipocyte diameters. The animals were kept in feeding experiments, 3 and 2 sectors respectively of growing period were examined (40 kg; 66 kg, 88 kg body mass) divided into 6 and 4 feeding levels respectively for 21 days (0.4; 0.6/0.8; 1.0; 1.2; 1.4 MJ metabolic energy per kg body mass0.75 per day). The inner layer of backfat showed bigger fat cells compared to the outer layer. The average fat cell size was greater for the older and heavier than for the younger animals. The gradation of food administration resulted not in a straight parallel rise in fat cell size but in an effective consequence with respect to the distribution frequency of the dates: The higher the food energy level, the more the accumulation of small fat cells from 10 til 30 microns diameter. These cell fractions succeeded in being signified as typical and important closed population. Other authors also had described these particular cells, i.e. "fat cell clusters" and "VSFC" (= very small fat cells) respectively. An external use of the dates for computer simulation programs resulted in success and manifested the independently gained conclusions. The examinations were performed by support of different branches of literature and the results had to be discussed in front of a wide background of known connections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317185 TI - [The problems of the estimation of bacterial contamination in viral drinking water vaccines for poultry]. AB - The definition of saprophytic and non pathogenic germs according to the DAB 9 (German Pharmacopeia) will be explained as follows. Germs should be seen as saprophytic and non pathogenic when they are either classified as a pathogen by biochemical methods or when the safety test in chickens shows no adverse local or clinical reactions. The reason for the different test results in testing the species and the amount of contaminating germs at the laboratories of vaccine producers and state laboratories are explained by the unequal dissemination of germs in each batch and by the discontinuity in cooling the vaccine samples. PMID- 2317186 TI - [Pathological changes in Streptobacillus moniliformis infection of C57bl/6J mice]. AB - An epizootic disease caused by Streptobacillus moniliformis occurred in C57BL/6J mice. Pathological lesions included abscessation of lymph nodes and chronic polyarthritis and osteomyelitis. Histological features of the disease are described. The most important differential diagnosis, infectious ectromelia of mice, is discussed. PMID- 2317187 TI - [A non-systemic skeletal disease in a cat--a case report]. AB - A report is given on a skeleton disease in a cat, mainly demonstrating an extraordinary severe coxarthrosis. PMID- 2317188 TI - [The use of a test phantom in step-shaped forms (test steps) for the clarification of different problem situations in x-ray diagnosis. 1. The use of test steps for the estimation of image quality after modified darkroom technics]. AB - Properly exposed radiographs and under- or overexposed ones were processed differently with regard to temperature and time. Using a step wedge for the objective estimation, the alteration of well-exposed radiographs by neglecting time and temperature control was examined. Further information is given about the possibility to improve the quality of wrongly exposed radiographs by manipulation of the processing, and about the quantity of acceptable radiographs received in this way. Stop bath, fixation bath, wash bath and drying were performed regularly. The result showed, that the only chance to get high quality radiographs is by exact and correct working. PMID- 2317190 TI - Both the outer mitochondrial membrane and the microsomal forms of cytochrome b5 reductase contain covalently bound myristic acid. Quantitative analysis on the polyvinylidene difluoride-immobilized proteins. AB - NADH-cytochrome b5 reductase is known to be located on two distinct membranes, i.e. endoplasmic reticulum and outer mitochondrial membranes. The endoplasmic reticulum-associated form of the enzyme contains myristic acid in an amide linkage to its N-terminal glycine [Ozols, Carr & Strittmatter (1984) J. Biol. Chem. 259, 13349-13354]. To investigate whether the dual subcellular localization of the reductase corresponds to a difference in fatty acylation, the enzyme was purified from well-characterized rat liver microsomal and mitochondrial fractions and analysed by a new quantitative analytical procedure. The purified reductases were run on SDS/polyacrylamide gels and blotted on to polyvinylidene difluoride membranes. The reductase-containing bands were treated with hydroxylamine, and amide-linked fatty acids were then detached by acid hydrolysis. The detached fatty acids were extracted, derivatized and analysed as phenylacyl esters by reverse-phase h.p.l.c., and the protein content of the samples was determined by amino acid analysis of the acid hydrolysates. Myristic acid was found in both the microsomal and mitochondrial reductases in a molar ratio of 1:1 with protein. These results demonstrate for the first time the presence of a myristylated protein on outer mitochondrial membranes, and show that the microsomal and mitochondrial reductases are also identical in their fatty acylation. PMID- 2317189 TI - Manganese and calcium efflux kinetics in brain mitochondria. Relevance to manganese toxicity. AB - Manganese shares the uniport mechanism of mitochondrial calcium influx, accumulates in mitochondria and is cleared only very slowly from brain. Using dual-label isotope techniques, we have investigated both Mn2+ and Ca2+ mitochondrial efflux kinetics. We report that (1) there is no significant Na(+) dependent Mn2+ efflux from brain mitochondria; (2) Mn2+ inhibits both Na(+) dependent and Na(+)-independent Ca2+ efflux in brain, in a mode that appears to be primarily competitive and with apparent Ki values of 5.1 and 7.9 nmol/mg respectively; and (3) Ca2+ does not appear to inhibit Mn2+ efflux from brain mitochondria. Findings (1) and (2) suggest the possibility of mitochondrial accumulation of both Mn2+ and Ca2+ in Mn2(+)-intoxicated brain. PMID- 2317191 TI - Lipoprotein lipase and hepatic lipase activities in a hypercholesterolaemic (RICO) strain of rat. Effect of dietary cholesterol. AB - Hepatic lipase (HL) and lipoprotein lipase (LPL) were assayed in heparinized plasma from male normocholesterolaemic (SW) and genetically hypercholesterolaemic (RICO) rats. Both strains were fed on either a semi-purified control diet or the same diet enriched with 0.5% or 1% cholesterol. HL activity was similar in both groups of rats fed on the control diet. LPL activity was found to be significantly lower in RICO rats (35% decrease, P less than 0.05). Feeding with a high-cholesterol diet led to a decrease in HL activity (15-23%) in both groups of rats but no change was detected in LPL activity, which remained consistently lower in the RICO rats. Thus, with the control diet, LPL activity is lower in RICO rats but presumably is not rate-limiting for their triacylglycerol clearance, given the normal triacylglycerol levels present. After cholesterol feeding, however, the lower LPL activity may become rate-limiting together with the decrease in HL activity, as in these circumstances hypertriacylglycerolaemia was evident and the hypercholesterolaemia of this strain was further increased. PMID- 2317192 TI - Subcellular biosynthesis and transport of gangliosides formed from exogenous lactosylceramide in rat liver. AB - In order to clarify the mechanisms of ganglioside biosynthesis and transport we intravenously administered a liposomal dispersion of radiolabelled lactosylceramide (LacCer) to rats and then followed the time course of the individual gangliosides which became radioactive in the Golgi-apparatus and plasma-membrane fractions prepared from the liver. After administration of radiolabelled LacCer the liver retained a substantial amount of radioactivity, which was distributed among an organic phase (mainly residual LacCer), a fraction containing low-Mr substances (mainly 3H2O) and a ganglioside fraction. The hepatocytes were found to provide the bulk of gangliosides biosynthesized from exogenous LacCer. After subcellular fractionation, the total radioactive gangliosides increased in the Golgi apparatus up to 8 h, to then decrease and practically disappear at 24 h; in the plasma membranes they were progressively concentrated, accounting for high absolute values. Ganglioside patterns were greatly modified with time in both the Golgi apparatus and plasma membrane, but without significant differences between them. Biosynthesis in the Golgi apparatus and accumulation in the plasma membrane of each individual ganglioside followed a precursor-product relationship. The obtained results indicated that once a ganglioside is biosynthesized in the Golgi apparatus, it is in part made available for translocation to the plasma membrane, which rapidly occurs, and is in part retained in the Golgi apparatus, where it acts as a precursor for the biosynthesis of more glycosylated gangliosides. PMID- 2317193 TI - Study of the mode of action and site-specificity of the endo-(1----4)-beta-D glucanases of the fungus Penicillium pinophilum with normal, 1-3H-labelled, reduced and chromogenic cello-oligosaccharides. AB - The modes of action of the five major endo-(1----4)-beta-D-glucanases (I, II, III, IV and V) purified from Penicillium pinophilum cellulase were compared by h.p.l.c. analysis, with normal, 1-3H-labelled and reduced cello-oligosaccharides and 4-methylumbelliferyl glycosides as substrates. Significant differences were observed in the preferred site of cleavage even when substrates with the same number of glycosidic bonds were compared. Thus, although endoglucanase I was unable to attack normal cello-oligosaccharides shorter than degree of polymerization 6, it hydrolysed reduced cellopentaose to yield cellotriose and cellobi-itol, and it produced cellotriose and 4-methylumbelliferyl glucoside from 4-methylumbelliferyl cellotetraoside. Endoglucanase IV hydrolysed [1 3H]cellotriose but did not attack either cellotri-itol or 4-methylumbelliferyl cellobioside. These and other anomalous results indicated clearly that modification of the reducing glycosyl residue on the cello-oligosaccharides induces in an apparent change in the mode of action of the endoglucanases. It is suggested that, although cello-oligosaccharide derivatives are useful for differentiating and classifying endoglucanases, conclusions on the mechanism of cellulase action resulting from these measurements should be treated cautiously. Unequivocal information on the mode of endoglucanase action on cello oligosaccharides was obtained with radiolabelled cello-oligosaccharides of degree of polymerization 3 to 5. Indications that transglycosylation was a property of the endoglucanases were particularly evident with the 4-methylumbelliferyl cello oligosaccharides. Turnover numbers for hydrolysis of the umbelliferyl cello oligosaccharides were calculated, and these, along with the other analytical data collected on the products of hydrolysis of the normal, reduced and radiolabelled cello-oligosaccharides, suggested that the various endoglucanases had different roles to play in the overall hydrolysis of cellulose to sugars small enough to be transported through the cell membrane. PMID- 2317194 TI - Purification and characterization of a hyaluronan-binding protein from rat chondrosarcoma. AB - Swarm rat chondrosarcoma contains a hyaluronan-binding protein of molecular mass 102 kDa (HABP102). The protein is present in 4 M-guanidinium chloride extracts of the chondrosarcoma and can be incorporated into reconstituted proteoglycan aggregates, but it is not present in native proteoglycan aggregates or in 0.5 M guanidinium chloride extracts. HABP102 is unlikely to be an integral membrane protein, as it does not require detergent for extraction, is not enriched in hydrophobic amino acids and does not bind avidly to octyl-Sepharose. The protein stains poorly with Coomassie Blue and is only visible on PAGE gels after staining with silver. Disulphide bonds are essential for the binding of HABP102 to hyaluronan, and bivalent cations are not required for this interaction. HABP102 can be purified from dissociative chondrosarcoma extracts by sequential density gradient centrifugation, hyaluronan-Sepharose affinity chromatography and hydrophobic-interaction chromatography. The amino acid composition is similar to that of domains 1-4 of the chondrosarcoma proteoglycan core protein, but peptide analysis after digestion with Staphylococcus aureus V8 proteinase and chymotrypsin and different immunoreactivity suggest that HABP102 is not closely related to proteoglycan hyaluronan-binding region. HABP102 is a glycoprotein containing N-acetylgalactosamine, N-acetylglucosamine, mannose and galactose. PMID- 2317195 TI - P2-purinoceptor regulation of surfactant phosphatidylcholine secretion. Relative roles of calcium and protein kinase C. AB - Ca2+ and protein kinase C have both been proposed as intracellular signals for subsequent phosphatidylcholine secretion by alveolar Type II cells. We have determined the relative roles of Ca2+ and protein kinase C in regulating surfactant phosphatidylcholine secretion by utilizing exogenous ATP and the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) as secretagogues, along with MAPTAM to chelate intracellular Ca2+ and sphingosine to inhibit endogenous protein kinase C. Exposure of Type II cells to the P2-purinoceptor agonist, ATP, results in a dose-dependent increase in surfactant phosphatidylcholine secretion from isolated alveolar Type II cells with an EC50 (concn. producing 50% of maximal response) of 2 microM. Administration of exogenous ATP to Type II cells also results in a dose-dependent increase in inositol trisphosphate production, Ca2+ mobilization and [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding as a measure of protein kinase C translocation. The EC50 in each case is 1-5 microM, indicating association of these events with surfactant phosphatidylcholine secretion. Loading Type II cells with non-hydrolysable GTP analogue (GTP[S]) inhibited ATP-induced Ca2+ mobilization, supporting the hypothesis that Type II cell P2-purinoceptors are coupled to phospholipase C via a GTP-binding protein. The ATP-induced elevation of cytosolic Ca2+ was also inhibited by MAPTAM (a cell permeant EGTA analogue) by 90%, but MAPTAM was without effect on surfactant phosphatidylcholine secretion induced by ATP. Sphingosine inhibited both ATP- and TPA-induced surfactant phosphatidylcholine secretion as well as [3H]PDBu binding with a similar IC50 (concn. producing 50% of maximal inhibition) (10 microM). Sphingosine did not affect surfactant phosphatidylcholine secretion induced by terbutaline and did not have a significant effect on Ca2+ mobilization induced by exogenous ATP. These results are consistent with a prominent role for protein kinase C in regulation of P2-purinoceptor-induced surfactant phosphatidylcholine secretion, and indicate that Ca2+ mobilization is not a necessary step for ATP induced surfactant phosphatidylcholine secretion. PMID- 2317196 TI - Lipoamidase (lipoyl-X hydrolase) from pig brain. AB - Although the optimum substrate for lipoamidase (lipoyl-X hydrolase) has not yet been determined, it is known that lipoamidase activity, as determined by hydrolysis of the synthetic substrate lipoyl 4-aminobenzoate (LPAB), is widely distributed in pig brain tissues, i.e. in the cerebrum, cerebellum and medulla. Over 95% of the enzyme activity is present in the membrane subfractions, indicating that brain lipoamidase is an integral membrane protein enzyme. To elucidate the chemical nature and the optimum substrate of the abundant lipoamidase in the brain, we isolated it from the membrane subfractions. After an 8-step purification procedure, brain lipoamidase was purified 601-fold and identified as a 140 kDa glycoprotein by SDS/PAGE. A mechanistic study to determine Km and Vmax, values was carried out using various synthetic compounds. Lipoyl-lysine, which is generally believed to be a naturally occurring substrate of lipoamidase, was first compared with biotinyl-lysine, because these two vitamins have reactive sulphur atoms and are similar in molecular mass and structure. The Km for lipoyl-lysine was 333 microM, whereas biotinyl-lysine was not hydrolysed. Stringent specificity for the lipoyl moiety is demonstrated, as expected. Dipeptides of amino acid-lysine structures were studied, and dipeptides of aspartyl- and glutamyl-lysine hydrolysis occurred at high Km (3 mM) values. Thus lysine in the moiety is not very effective as an optimum substrate. The chemical bond structures of the amide bond (lipoyl-lysine) and peptide bond (aspartyl-lysine) were hydrolysed. Next, the ester bond compound was tested, and it was observed that lipolylmethyl ester was hydrolysed at high specificity. These findings indicate that this enzyme has broad specificities with respect to bond structure; it therefore is a unique hydrolase having stringent specificity for lipoic acid and relatively broad specificity for the chemical bond and the X moiety. Various inhibitors were tested; a few reagents, such as organic mercurials, di-isopropylfluorophosphate, 1,10-phenanthroline, sodium azide and angiotensin-converting enzyme inhibitor exhibited some inhibition (not more than 60%). Thus the active centre of this enzyme is a complex type. Although ATP is not hydrolysed and the lowest Km value is exhibited by the synthetic substrate reduced from LPAB (12 microM), some other compounds may still be expected to be hydrolysed by this unique and abundant brain lipoamidase. PMID- 2317197 TI - A continuous fluorescence displacement assay for the measurement of phospholipase A2 and other lipases that release long-chain fatty acids. AB - 1. A new continuous fluorescence assay for phospholipase A2 is described which involves the displacement of the highly fluorescent fatty-acid probe 11 (dansylamino)undecanoic acid from rat liver fatty-acid-binding protein by long chain fatty acids released as a result of phospholipase A2-catalysed hydrolysis of phospholipids. The initial rate of decrease in fluorescence is linearly related to enzyme activity. 2. The assay will detect enzyme activity down to about 10 pmol/min per ml and gives a linear response up to about 10 nmol/min per ml. 3. The assay will work with all phospholipids that have been tested including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and phosphatidylglycerol. Substrates carrying a net negative charge showed the highest rates of hydrolysis. 4. The assay will work, in principle, with an enzyme catalysing the release of long-chain fatty acids from a fatty-acylated substrate. This has been confirmed with pancreatic lipase and cholesterol esterase. PMID- 2317198 TI - Affinity labelling of 5'-nucleotidases with 5'-p-fluorosulphonylbenzoyladenosine. AB - 5'-Nucleotidases play an important role in the metabolism of nucleosides; for example, the hydrolysis of AMP generates adenosine, which can modulate a variety of cellular functions. We have used the membrane-bound AMPase from chicken gizzard and a secreted form of these enzymes to analyse their modification by the substrate analogue 5'-p-fluorosulphonylbenzoyladenosine (5'-FSBA). 5'-FSBA irreversibly inactivates 5'-nucleotidases by means of covalent modification of the proteins. ATP, a competitive inhibitor of chicken gizzard and snake-venom 5' nucleotidase, abolished the inactivation by 5'-FSBA, demonstrating that the inactivation was due to the modification of amino acid residues essential for AMPase activity. We have synthesized radioactive 5'-FSBA, which was employed for the radiolabelling of chicken gizzard 5'-nucleotidase. Incorporation of radioactivity was completely abolished in the presence of ATP, which showed that 5'-FSBA acted by the selective modification of amino acid residues at the active site whereas other potential reactive residues of the protein were not attacked. Limited proteolysis of affinity-labelled chicken gizzard 5'-nucleotidase permitted the identification of digestion products containing the catalytic centre. Pseudo-first-order kinetics indicate that modification of a minimum of one amino acid side chain at the active centre is sufficient to result in inactivation of both chicken gizzard and snake-venom 5'-nucleotidases. Incorporation of the radioactive p-sulphonylbenzoyladenosine moiety parallels the inactivation of 5'-nucleotidase by 5'-FSBA and further substantiated the idea that modification of one amino acid residue at the active centre results in loss of the AMPase activity. PMID- 2317199 TI - The accessibility of the thiol groups on G- and F-actin of rabbit muscle. AB - The accessibility of the cysteine residues of actin from rabbit muscles to the thiol-targeted reagent 7-dimethylamino-4-methyl-(N-maleimidyl)coumarin (DACM) was investigated. Under conditions where the actin is in the unpolymerized form (G actin), the most reactive thiol group was Cys-257, suggesting that it was located on the surface of the actin molecule. The selective modification of Cys-374 for this reagent as reported by Sutoh [(1982) Biochemistry 21, 3654-3661] was not observed. Cys-10, Cys-217 and Cys-374 were much less reactive and only gradually became extensively modified when the concentration of DACM approached 5 molar equivalents of actin. Presumably these thiol groups were located further inward away from the surface or situated in a different environment that rendered them less reactive. On the other hand, Cys-285 was completely inaccessible and presumably was buried. The lack of preferential labelling of Cys-374 by DACM is incompatible with the finding with iodoacetic acid as the reagent as reported by Elzinga & Collins [(1975) J. Biol. Chem. 250, 5897-5905]. This discrepancy, however, might well be due to the different reagents employed. The DACM-G-actin largely retained its competence for polymerization. Upon polymerization of G actin, practically all the thiol groups became inaccessible to DACM, suggesting that a drastic change occurred in the conformation of actin units in the transition of monomers to filamentous actin. PMID- 2317200 TI - Rat spleen glutathione transferases. A new acidic form belonging to the Alpha class. AB - Cytosolic glutathione transferases (GSTs) were purified from the rat spleen by S hexyl-GSH-Sepharose chromatography, and two major forms were identified as GSTs 2 2 and 7-7 (GST P). Besides these forms an acidic form (pI 5.8) was purified by chromatofocusing at pH 7-4 and it accounted for about 1% of the total GST activity bound to S-hexyl-GSH-Sepharose. Two-dimensional gel electrophoresis revealed that it is a homodimer (subunit Mr 26,000 with pI 5.8). Immunoblot analysis demonstrated that it was immunologically related to GSTs 2-2 and 1-1, and its N-terminal amino acid was apparently blocked, similarly to other forms of the class Alpha. This form had a low activity towards cumene hydroperoxide or 4 hydroxynon-2-enal, indicating that this form differed from GSTs 10-10 and 8-8 as well as from GSTs 1-1 and 2-2. These results suggest that it is a new form of GST belonging to the class Alpha. PMID- 2317201 TI - Hydrolysis of fucosyl-GM1 ganglioside by purified pellet-associated human brain and human liver alpha-L-fucosidases without activator proteins or detergents. AB - Pellet-associated human brain alpha-L-fucosidase was solubilized with 0.5% (w/v) Triton X-100 and purified by affinity chromatography on agarose-6-aminohexanoyl fucosamine resin. The procedure resulted in a 290,000-fold purification, a 58% yield and a final specific activity of 11,500 nmol/min per mg of protein. Isoelectric focusing indicated that all six major isoforms (with pI values between 4.1 and 5.3) present in crude brain pellet preparations were purified by the affinity technique. SDS/PAGE indicated the presence of one subunit (54 kDa) and a minor protein band at 67 kDa, which presumably is a contaminant since it was not immunoreactive on Western blotting. The pH optimum of the brain enzyme and its apparent Km for the synthetic substrate 4-methylumbelliferyl alpha-L fucopyranoside were 5.5 and 0.07 mM respectively. Pellet-associated human brain and liver alpha-L-fucosidases were both capable of hydrolysing fucosyl-GM1 ganglioside without activator proteins or detergents. Linear hydrolysis rates were found only for short incubation times (1-5 min). Optimal enzymic activity at 37 degrees C was found at pH 3.4 for both alpha-L-fucosidases, with no activity at pH values above 4.0. PMID- 2317203 TI - Photoaffinity labelling of isopenicillin N synthetase. AB - The alpha-aminoadipoyl group of the natural substrate of isopenicillin N synthetase (IPNS), L-alpha-aminoadipoyl-L-cysteinyl-D-valine (ACV), has been replaced by a diazirinyl-containing group, which can be photoactivated. This has allowed investigation of the substrate binding site of IPNS by photoaffinity labelling. Laser flash photolysis of this analogue, [3H]DCV, in the presence of IPNS leads to the incorporation of radioactivity into the enzyme. Tryptic digestion of this labelled enzyme, followed by separation and sequencing of the resultant fragments, identified two labelled regions of the protein. These are the fragments Asp-40 to Arg-78 and Thr-237 to Gly-256. PMID- 2317202 TI - Stimulus-response coupling in human platelets activated by monoclonal antibodies to the CD9 antigen, a 24 kDa surface-membrane glycoprotein. AB - The CD9 molecule is a 24 kDa surface-membrane glycoprotein present on platelets and a variety of haematopoetic and non-haematopoetic tissues. In the present study we utilized specific inhibitors of thromboxane A2 (TxA2) formation (aspirin), protein kinase C [H-7 [1-(5-isoquinolinesulphonyl)-2 methylpiperazine]] and autocrine stimulation by secreted ADP (apyrase) to modify platelet activation by a monoclonal antibody ALB-6 to the CD9 antigen. This activation is only partially inhibited by aspirin alone but, in combination with either H-7 or apyrase, more than 50% inhibition of platelet aggregation and secretion was observed. This combination of inhibitors was also required to inhibit effectively the phosphorylation of myosin light chain and the 47 kDa substrate of protein kinase C. Intracellular Ca2+ flux monitored by the fluorescent dye fura-2 showed that this was almost completely mediated by the aspirin-sensitive TxA2 pathway. We suggest that the aspirin-insensitive pathway is primarily mediated by phospholipase C formation of diacylglycerol to activate protein kinase C. The inhibition by apyrase suggests a strong dependency on autocrine stimulation by secreted ADP to fully activate both phospholipase C and express fibrinogen-binding sites mediating platelet aggregation. This alternate pathway of phospholipase C activation by ALB-6 may be mediated by cytoplasmic alkalinization [monitored by SNARF-1 (5'(6')-carboxy-10-bismethylamino-3-hydroxy spiro-[7H- benzo[c]xanthine-1',7(3H)-isobenzofuran]-3'-one) fluorescence of the dye]. Both activation pathways are dependent on intact antibodies, since F(ab')2 fragments of SYB-1, a monoclonal antibody against the CD9 antigen with activation characteristics identical with those of ALB-6, do not elicit activation. Besides thrombin, collagen is another physiological agonist shown to induce aspirin insensitive activation. Similarities to ALB-6 in collagen sensitivity to apyrase in combination with aspirin inhibitors were noted with respect to aggregation and secretion, as well as a complete block of Ca2+ flux by aspirin. However, it is unlikely that collagen activation is mediated by the CD9 antigen, since SYB-1 F(ab')2 fragments had no effect on collagen activation and aspirin also completely blocked the alkalinization response to collagen, in contrast with ALB 6. PMID- 2317204 TI - Cartilage proteoglycan aggregate is degraded more extensively by cathepsin L than by cathepsin B. AB - The degradative actions of cathepsins L and B on human articular-cartilage proteoglycan aggregates were examined. Cathepsin L was found to be much more extensive than cathepsin B in degrading proteoglycan aggregates. It released products with size similar to that of single chondroitin sulphate chains, and a series of degraded link-protein fragments in the digestion mixtures. These proteolytically modified link-protein components (Mr 25,000 and 33,000) have similar Mr values to those of fragments observed in adult human cartilage. In contrast, cathepsin B exhibited a much more limited degradation on both proteoglycan subunits and link-protein components. Both cathepsins L and B generate multiple but distinct cleavage sites on human link proteins, and the hydrolysed bonds have been identified in the region between residues 18 and 29. Protein sequencing analysis of these modified link-protein components also provided evidence for the location of a second N-linked glycosylation site at residue 41 in human link proteins, in addition to that previously described at residue 6 on a proportion of the link proteins. Furthermore, it allows us to report the sequence of human link protein up to residue 65. PMID- 2317205 TI - Demonstration of 3 alpha(17 beta)-hydroxysteroid dehydrogenase distinct from 3 alpha-hydroxysteroid dehydrogenase in hamster liver. AB - NAD(+)-linked and NADP(+)-linked 3 alpha-hydroxysteroid dehydrogenases were purified to homogeneity from hamster liver cytosol. The two monomeric enzymes, although having similar molecular masses of 38,000, differed from each other in pI values, activation energy and heat stability. The two proteins also gave different fragmentation patterns by gel electrophoresis after digestion with protease. The NADP(+)-linked enzyme catalysed the oxidoreduction of various 3 alpha-hydroxysteroids, whereas the NAD(+)-linked enzyme oxidized the 3 alpha hydroxy group of pregnanes and some bile acids, and the 17 beta-hydroxy group of testosterone and androstanes. The thermal stabilities of the 3 alpha- and 17 beta hydroxysteroid dehydrogenase activities of the NAD(+)-linked enzyme were identical, and the two enzyme activities were inhibited by mixing 17 beta- and 3 alpha-hydroxysteroid substrates, respectively. Medroxyprogesterone acetate, hexoestrol and 3 beta-hydroxysteroids competitively inhibited 3 alpha- and 17 beta-hydroxysteroid dehydrogenase activities of the enzyme. These results show that hamster liver contains a 3 alpha(17 beta)-hydroxysteroid dehydrogenase structurally and functionally distinct from 3 alpha-hydroxysteroid dehydrogenase. PMID- 2317207 TI - Isolation and partial characterization of an extradiol non-haem iron dioxygenase which preferentially cleaves 3-methylcatechol. AB - A purification procedure has been developed for an extradiol dioxygenase expressed in Escherichia coli, which was originally derived from a Pseudomonas putida strain able to grow on toluidine. Physical and kinetic properties of the enzyme have been investigated. The enzyme has a subunit Mr of 33,500 +/- 2000 by SDS/polyacrylamide-gel electrophoresis. Gel filtration indicates a molecular mass under non-denaturing conditions of 120,000 +/- 20,000. The N-terminal sequence (35 residues) of the enzyme has been determined and exhibits 50% identity with other extradiol dioxygenases. Fe(II) is a cofactor of the enzyme, as it is for other extradiol dioxygenases. The reactivity of this enzyme towards catechol and methyl-substituted catechols is somewhat different from that seen for other catechol 2,3-dioxygenases, with 3-methylcatechol cleaved at a higher rate than catechol or 4-methylcatechol. Km values for these substrates with this enzyme are all around 0.3 microM. The enzyme exhibits a bell-shaped pH profile with pKa values of 6.9 +/- 0.1 and 8.7 +/- 0.1. These results are compared with those found for other extradiol dioxygenases. PMID- 2317206 TI - The disulphide-bond content and rheological properties of intestinal mucins from normal subjects and patients with cystic fibrosis. AB - The disulphide/thiol (S-S/SH) content and rheological properties of highly purified small-intestinal mucins from normal (N) subjects and patients with cystic fibrosis (CF) were investigated. (1) An assay was developed to measure free SH groups (before reduction) and total SH content (after reduction) using 4,4'-dipyridyl disulphide. S-S bonds were calculated by difference. Experimental values for the S-S and SH contents of well-characterized proteins obtained with the assay showed good agreement with expected values. (2) The S-S and free SH contents of nine N and six CF mucins were variable: 44.4 +/- 5.4 nmol of S-S and 4.3 +/- 1.1 nmol of free SH per mg of N mucin and 31.7 +/- 7.6 nmol of S-S and 7.5 +/- 3.7 nmol of SH per mg of CF mucin. N and CF mucins were not statistically different. In most mucins, approximately 90% of the SH groups were involved in S S bonds. (3) Gels were reconstituted from the same N and CF mucins at concentrations between 8 and 25 mg/ml and their rheological properties were assessed by using a magnetic microrheometer. (4) Once formed, mucin gels were stable and maintained the same mechanical properties over a long period of time (3-14 days). (5) The rheological profiles of both N and CF samples did not vary with the concentration of mucin present and were characteristic of weak, visco elastic gels. (6) Although variations were seen in the visco-elastic properties of individual mucins, no systematic differences were detected between N and CF preparations. (7) There was no apparent correlation between the rheological properties of a mucin and its S-S/SH content. PMID- 2317208 TI - Genetic characterization of an alloalbumin, albumin Kashmir, using gene amplification and allele-specific oligonucleotides. AB - The molecular basis for albumin Kashmir was studied using the polymerase chain reaction to amplify a DNA fragment containing codon 501 in exon 12 of the human albumin gene. Southern blots of the amplified DNA were hybridized to oligonucleotide probes specific either for the normal allele of albumin or for albumin Kashmir. The results provide strong evidence that codon 501 in albumin Kashmir is AAG (lysine) instead of GAG (glutamic acid), thus confirming the protein sequences reported. This approach was used to characterize a bisalbuminaemic individual as a carrier for albumin Kashmir. Similar strategies may be devised to study the molecular basis and to identify carriers of other alloalbumins. PMID- 2317209 TI - The pathophysiological significance of increased tight-junctional permeability during oestrogen cholestasis. PMID- 2317211 TI - Bone morphogenetic protein 1 is homologous in part with calcium-dependent serine proteinase. PMID- 2317210 TI - Oestradiol 17 beta-glucuronide and tight junctional permeability increase. PMID- 2317212 TI - Kinetic parameters governing the formation of eIF-2.methionyl-tRNAi complexes in protein synthesis. AB - Published data have been analysed to determine the rate constants governing the exchange of GDP in the complex of the eukaryotic protein synthesis initiation factor eIF-2 with GDP, catalysed by eIF-2B. The interaction of eIF-2B with eIF 2.GDP appears to include a very high 'on' rate constant of up to 4 x 10(8) M-1 sec-1 - a value very similar to that found by others for the interaction of the bacterial elongation factors Tu and Ts. Assuming a substituted enzyme mechanism that leads to displacement of GDP and ultimately to formation of a quaternary complex eIF-2B.eIF-2.GTP.methionyl-tRNA, minimum rate constants have been estimated for the additional reactions assuming in vivo rates of protein synthesis. Rate constants for the other reactions are unexceptional. PMID- 2317213 TI - Isolation and characterization of hyaluronidase from scorpion (Heterometrus fulvipes) venom. AB - Hyaluronidase (Hyaluronate lyase, E.C. 3.2.1.35) has been isolated from Heterometrus fulvipes scorpion venom by a combination of gel filtration on Sephadex G-75 and ion exchange chromatography on DEAE-cellulose. The enzyme preparation showed a single band on polyacrylamide gel electrophoresis and a molecular weight of 82,000. The final preparation was purified 27-fold. The optimum pH for enzyme activity was 4.0. No loss of activity was observed up to 30 degrees C and showed a sharp decrease in activity at 50 degrees C. Heparin inhibited the enzyme activity. PMID- 2317214 TI - Protease inhibitors reduce lysosomal acid phospholipase A1 activity in cultured rat hepatocytes. AB - When rat hepatocytes were cultured in the presence of various specific protease inhibitors, lysosomal acid phospholipase A1 activity decreased progressively. Exposure of the cultured cells to 0.1 micrograms/ml of pepstatin, E 64, leupeptin or chymostatin also reduced the catalytic activities of several lysosomal marker enzymes. Irrespective of the protease inhibitor type employed, acid phospholipase A1 activity reacted most sensitively, followed by acid phosphatase, acid beta-N acetyl-D-hexosaminidase and acid beta-glucuronidase. Of the protease inhibitors studied, pepstatin appeared to be most potent in reducing lysosomal enzyme activities in cultured hepatocytes. These findings suggest that proteolytic processes at as yet unknown, possibly extralysosomal sites play an important role in the turnover rates of lysosomal enzymes. PMID- 2317215 TI - Isomer specific kinetics of dopamine beta-hydroxylase and arylsulfatase towards catecholamine sulfates. AB - Both isomers of epinephrine sulfate were synthesized, unequivocally identified by 1H-NMR and highly purified from catecholamines (less than 90 ppm). Bacterial as well as pig liver arylsulfatase A and B demonstrated a higher substrate turnover of epinephrine-4-sulfate, norepinephrine-4-sulfate and dopamine-4-sulfate as compared to the 3-sulfate isomers. The arylsulfatase B however, is less important for the deconjugation of these sulfoconjugates than arylsulfatase A. Since arylsulfatase A occurs in most human tissues, it might be of physiological significance in the deconjugation of the catecholamine sulfate isomers. Furthermore the kinetic data at pH 7.4 and 6.9 suggest the increased cleavage of the sulfate group, e.g. during exercise-induced acidosis. In contrast to results reported in the literature, dopamine sulfates were no substrates of dopamine beta hydroxylase. PMID- 2317216 TI - In vivo C14-L-alanine metabolism in rat dietary obesity induced by cafeteria diet. AB - The "in vivo" handling of L-alanine in 24 hours starved rats, in which obesity was induced by feeding with cafeteria diet, was compared with that of starved control rats. 14C-alanine was administered in trace amounts in order not to affect the normal handling of this amino acid. The results obtained in blood and liver support a lowered glucose formation from alanine. The specific radioactivities corresponding to lactate, glutamate + glutamine and asparagine as well as total protein and total lipid, were all lowered in the obese group. This strongly suggests that glucose formation from alanine in the liver was impaired. The specific radioactivity of the metabolites studied in the striated muscle are compatible with the above suggestion. It can be concluded that the glucose alanine cycle operation is inhibited in the cafeteria diet starved obese rats. PMID- 2317217 TI - Accumulation of oleate-rich cholesteryl esters by acetyl-LDL in macrophages in the presence of an acyl-CoA: cholesterol acyltransferase inhibitor (Sandoz 58 035). AB - The mechanism through which cholesteryl esters rich in oleic acid accumulate in the cytoplasm was studied. The fatty acid composition of the cholesteryl esters in acetyl-LDL was high in linoleic acid, while that of cholesteryl ester inclusion bodies accumulated in the cytoplasm was high in oleic acid. This compositional change of fatty acids in cholesteryl esters occurred even in the presence of an acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, Sandoz 58 035. These results suggest that oleate-rich cholesteryl esters accumulated in the cytoplasm, even though the reesterification in microsome was inhibited by an ACAT inhibitor. PMID- 2317218 TI - A study of the intracellular effects of glutathione by 1H-spin echo NMR of intact human erythrocytes. AB - The effect of adding either reduced (GSH) or oxidized (GSSG) glutathione to intact human erythrocytes was investigated by 1H-spin echo NMR, which allows direct observation of relatively concentrated low molecular weight compounds within intact cells. A specific region of the spectrum was affected by addition of GSH, with the appearance of new peaks that were diagnostic of an increase of intracellular GSH. These changes did not occur in hemolysates, and did not involve extra-cytosol GSH either free or membrane-bound. These results indicate that the intracellular redox balance of glutathione is shifted toward the reduced state by exogenous glutathione, possibly via a signal transferring system of the cell membrane. PMID- 2317219 TI - Purification and properties of buffalo serum albumin. AB - Based on a detailed study of the solubility of serum albumin, a procedure for its purification by selective ammonium sulphate precipitation has been developed. Using buffalo serum, first extraneous proteins were precipitated by making the serum 2.26 M saturated with ammonium sulphate at pH 7.0 and then albumin was precipitated from the supernatant at 1.9 M ammonium sulphate concentration at pH 4.2. The overall yield of serum albumin thus isolated was about 55% with a purity of 97%. The protein preparation gave a single nearly symmetrical peak on Sephadex G-100 column and virtually a single band on polyacrylamide gel electrophoresis in the presence and absence of SDS. Buffalo serum albumin has a molecular weight of 69,000 Da. The hydrodynamic properties such as Stoke's radius (3.70 nm), diffusion coefficient (6.03 X 10(-7) cm2/s) and frictional ratio (1.36) obtained by analytical gel chromatography, bilirubin binding characteristics and its interaction with anti-bovine serum albumin antiserum suggest that buffalo serum albumin is very similar to BSA in its molecular properties. PMID- 2317221 TI - The spectrum of atlantoaxial facet joint involvement in rheumatoid arthritis. AB - Six hundred fifty outpatients with rheumatoid arthritis (RA) were evaluated and followed up during a 7-year period. As part of their routine evaluation or because of neck-shoulder girdle symptoms, 48% of the patients underwent routine cervical spine radiography. Sixty-one RA patients (9% of the total population) had C1-C2 involvement. Compared with the 589 patients with no evidence of C1-C2 involvement, these 61 patients were significantly more likely to be younger, female, and seropositive, and they had significantly more nodules and erosions, as well as a longer disease duration. Based on radiographic evidence of C1-C2 disease severity, 3 groups emerged. Group 1 (28 patients) had lateral mass collapse, group 2 (27 patients) had lateral facet joint sclerosis, erosion, or loss of joint space with no collapse, and group 3 (6 patients) had lateral subluxation with no bone or cartilage changes. Nine patients in group 1 had severe pain, and 25 had a nonreducible rotational tilt of the head. None of the patients in the other 2 groups had either of these signs or symptoms. Moreover, patients in group 1 were more likely to have other C1-C2 or subaxial subluxations and were more likely to have myelopathy. C1-C2 lateral facet joint involvement is common in RA, correlates with disease severity generally and specifically with that in the cervical spine, and, when severe, causes nonreducible rotational tilt of the patient's head. PMID- 2317220 TI - Nucleotide sequence of a cDNA encoding the lipoate acetyl transferase (E2) of human heart pyruvate dehydrogenase complex differs from that of human placenta. AB - Tissue specific isoforms of an enzyme autoantigen were sought in an attempt to explain a possible disease-associated translocation of the enzyme. A human heart cDNA clone (0.66 kb) coding for part of the lipoate acetyl transferase component of pyruvate dehydrogenase complex, recently identified as one of the major autoantigens of primary biliary cirrhosis was isolated. The cloned cDNA corresponded to nucleotides 1545-2201 of a previously published placental sequence, but showed some differences which give rise to differences in the inferred amino acid sequences of proteins. This may indicate the existence of tissue-specific isoforms of the lipoate acetyl transferase component of pyruvate dehydrogenase complex coded for by a multi-gene family. PMID- 2317222 TI - Enhanced binding of lupus sera to the polyamine-induced left-handed Z-DNA form of polynucleotides. AB - The natural polyamines putrescine, spermidine, and spermine are small polyvalent cations present in all living cells. Spermidine and spermine are excellent promoters of left-handed Z-DNA, an immunogenic form of DNA that binds readily with anti-DNA antibodies in the sera of patients with systemic lupus erythematosus (SLE). We studied the binding of a panel of 16 SLE sera to poly(dA dC).poly(dG-dT) and poly(dG-m5dC).poly(dG-m5dC) in the presence and absence of spermidine and spermine using an enzyme-linked immunosorbent assay. The majority of SLE sera showed a 50-150% mean increase in optical density values when incubated with the polynucleotides and either 0.25 mM spermidine or 0.025 mM spermine than when incubated with the polynucleotides alone. Under these conditions, the polynucleotides assumed the Z-DNA form. Since polyamines are ubiquitous cellular components and since potential Z-DNA-forming alternating purine-pyrimidine sequences are widely dispersed in native DNA, the increased binding of SLE sera to polyamine-induced Z-DNA suggests a pathogenic role for these compounds in SLE. PMID- 2317223 TI - Soluble interleukin-2 receptors in patients with systemic sclerosis. Clinical and laboratory correlations. AB - Plasma levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked immunosorbent assay in 79 patients with systemic sclerosis (SSc). These levels were significantly elevated in SSc patients, compared with normal controls (mean +/- SEM 866.0 +/- 63.6 units/ml versus 293.0 +/- 20.5; P less than 0.001). Soluble IL-2R levels were highest in patients with generalized disease, were strongly associated with mortality (P less than 0.001) and inversely correlated with disease duration (P = 0.003), but were not related to sex, age, specific visceral involvement, serologic status, peripheral lymphocyte count, or therapy. Levels of sIL-2R in the supernatants of peripheral blood mononuclear cells were low in patients and controls, and showed comparable increases following phytohemagglutinin stimulation. Exposure of peripheral blood mononuclear cells to laminin did not induce sIL-2R release. Circulating IL-2 levels were comparably low in patients and controls. Our findings suggest the presence of lymphocyte activation in SSc, and further suggest that measurement of sIL-2R may prove to be a useful laboratory technique for assessing disease activity. PMID- 2317224 TI - High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice. AB - We administered a standardized history questionnaire and performed a tender point examination on 27 patients with debilitating fatigue of at least 6 months duration, seen in a primary care practice, as well as on 20 patients with fibromyalgia. Sixteen of the 27 patients with chronic fatigue met the full criteria for the working case definition of chronic fatigue syndrome (CFS). Eight patients with chronic fatigue denied having any current persistent, diffuse musculoskeletal pain, and their tender point scores were similar to those in 10 normal control subjects. In contrast, 19 patients with chronic fatigue (70%) had persistent, diffuse musculoskeletal pain. The results of their tender point examinations were similar to those of the patients with fibromyalgia. Thus, the majority of these patients with debilitating chronic fatigue, including those who met criteria for CFS, met the historical and tender point diagnostic criteria for fibromyalgia. The presence of current musculoskeletal pain will identify those CFS patients who have fibromyalgia. PMID- 2317225 TI - Atypical presentations of polymyalgia rheumatica. AB - Seventy patients with polymyalgia rheumatica (PMR) were seen at a suburban rheumatology practice from July 1983 to December 1987. Six of these patients presented without the typical limb girdle features associated with PMR. Presenting symptoms included peripheral synovitis or unilateral shoulder pain (3 patients), lower leg pain (3 patients), carpal tunnel syndrome (1 patient), and abdominal pain (1 patient). The disease evolved into the recognizable syndrome of PMR over a period of 2-12 months. We suggest that PMR may present in a variety of guises, or have a "stuttering evolution" to the full syndrome. The presenting manifestations of these atypical cases result from peripheral synovitis and thus represent a variant of the more common subclinical proximal synovitis seen in PMR. Increased clinical awareness of atypical presentations may assist earlier diagnosis and effective treatment. PMID- 2317226 TI - Associations between clinical status questionnaire scores and formal education level in persons with systemic lupus erythematosus. AB - In a study of 124 systemic lupus erythematosus patients, clinical status, according to 5 questionnaire scales, was poorer in patients with less than or equal to 11 years versus those with greater than or equal to 12 years of formal education. These results were statistically significant when adjusted for age, race, sex, and disease duration, though results on some scales were not significant when adjusted for multiple comparisons. These findings further support observations that formal education level is associated with clinical status in rheumatic and other chronic diseases. PMID- 2317227 TI - Pelvic insufficiency fractures. PMID- 2317229 TI - Another colloquy at Delphi: an unabashed parody. PMID- 2317228 TI - Mycobacteria and rheumatoid arthritis. PMID- 2317230 TI - Response. Marketing and the American College of Rheumatology: a professional approach for a professional society. PMID- 2317231 TI - Magnetic resonance imaging of the knee and hip. PMID- 2317232 TI - Regarding methotrexate pricing. PMID- 2317233 TI - The early use of disease-modifying antirheumatic drugs in rheumatoid arthritis. PMID- 2317234 TI - Differences between radiographic abnormalities of acromegalic arthropathy and those of osteoarthritis. PMID- 2317235 TI - Developing quality assurance programs in the occupational health setting. AB - It is important in the delivery of quality nursing care to have a system in place to evaluate the care administered. It is the responsibility of the profession to develop such a system, which is done in nursing through quality assurance programs. Quality assurance programs are based on standards of practice and peer review systems. Occupational health nurses are somewhat unique in their work situations and often need to develop creative strategies for quality assurance programs. The criteria used to evaluate nursing care may be developed to look at the structure, process, or outcome of nursing care. The model for implementation of quality assurance programs involves seven steps. PMID- 2317236 TI - Quality of care in occupational health through nursing diagnosis. AB - Nursing diagnosis as a part of nursing is not a new activity, but rather one that has been more clearly delineated and structured. Nursing diagnosis is the natural outcome following nursing assessment, and directs the establishment of care goals. Nursing diagnosis promotes quality of care by providing a common framework for the description of client needs, by delineating the areas of nursing responsibility, and by providing criteria to measure the comprehensiveness of the care provided. Consistency in terminology and structure is important for the effectiveness of nursing diagnosis. The use of a widely accepted diagnostic label promotes a clear understanding of the nurse's intended statement of the client's condition. Although consistency and standardization are features of the taxonomy of nursing diagnosis, the concept is flexible enough to be used in a variety of care settings. In occupational health nursing, this flexibility is provided through use of group data, through the diagnostic category of health maintenance, and by the identification of potential nursing diagnoses. PMID- 2317237 TI - Peer review: self help for occupational health nurses. AB - Nurses validate their actions with other nurses whose knowledge and skills they value. Where opportunities for evaluation do not exist, enthusiasm and creativity can wane. Peer review is a process that includes education, case writing, evaluation, and research. Peer review is not punitive. It is a professional review and has no place in personnel records or periodic evaluation by one's supervisors. Local constituencies can provide peer review programs for their members as part of their monthly meetings. PMID- 2317238 TI - Prenatal education and family centered health promotion at the worksite. PMID- 2317240 TI - Effective decision making. PMID- 2317239 TI - Educating women about benign breast disease. AB - The occupational health nurse can be a valuable resource for women by teaching how their bodies work and how female hormones affect their breasts. Nurses who work in primary care should view their role as one of education and advocacy on behalf of the client. Nurses can model a healthy attitude about breast self examination, encouraging women to perform it and to discuss openly their questions and concerns. Women should be encouraged to have mammograms, following ACS guidelines: a baseline mammogram between the ages of 35 and 40, a mammogram every 1 to 2 years between the ages of 40 and 49, and a yearly mammogram after age 50. PMID- 2317241 TI - Geographic variation of mortality in Greenland. Economic and demographic correlations. AB - Geographic variation of mortality in the native (Inuit) Greenlandic population was studied and compared at community level with income, population change and community size. Six well defined geographic regions were identified. Mortality rates from infectious diseases and accidents were lowest in West Greenlandic towns and highest in settlements and in East Greenland; they showed a significant negative correlation with income. Mortality rate from ischaemic heart disease was highest in West Greenlandic towns excluding the capital (Nuuk) while no clear geographic pattern was observed for cerebrovascular disease. The suicide rate was very high in the capital and in East Greenland while it was low, at the Danish level, in West Greenlandic settlements. The study has demonstrated an internal variation in the Greenlandic mortality pattern which must be taken into account in the planning of both scientific studies and practical health interventions. PMID- 2317242 TI - Inuit suicides in Greenland. AB - The increased frequency of suicide among Inuit in the North is reviewed and compared with an analysis of public files on suicides in Greenland 1977-86. From these files some kind of small scale "psychological" autopsy is performed, and the material is analyzed in relation to theories of socialization and acculturation. PMID- 2317243 TI - Playwork as a tool in the socialization of an Inuit child. PMID- 2317244 TI - Lactate does facilitate oxygen unloading from the hemoglobin of the whale, Balaenoptera acutorostrata, after diving. AB - The present study reports on a specific effect of lactate on the oxygen binding properties of the hemoglobin from the whale, Balaenontera acutorostrata. In fact 0.1 mM lactate may increase the amount of oxygen unloaded to the tissues as much as 30%. Under these conditions the Bohr shift, of the magnitude of about -1, does not alter the oxygen affinity, but plays an important role in the isohydric transport of carbon dioxide. PMID- 2317245 TI - Ectopic pregnancy in Greenland. An epidemiological study. AB - A retrospective epidemiological investigation was carried out to study the rate and incidence of ectopic pregnancy (EP) in Greenland. Data from 7 of Greenland's 16 medical districts, representing 48% of the population, were available for analysis covering the years 1980-1984. A total of 4481 pregnancies were reported, including 105 cases of EP. A rate of EP 2.34 was calculated, one of the highest on record, and significantly higher than Scandinavian figures representing the same period. Estimated from our figures there would be 44 cases of EP annually in Greenland. Annual fluctuations, however, were seen, and a positive correlation was found to notified cases of Neisseria infections. Significance from the null hypothesis, however, was only found at the 10% level. PMID- 2317247 TI - The Velo-Cardio-Facial (Shprintzen) syndrome. PMID- 2317246 TI - [Cardiology in rural areas]. AB - Based on a personal experience after having established a cardiology clinic in the town of Arroyo (Puerto Rico), we analyzed the patient population served and the services that were rendered. After collecting the data from the clinical files, we were able to obtain information on diagnosis, follow-up, diagnostic test and therapeutic procedures performed. In general, it was found that only a minority of patients needed long term cardiology follow-up and specialized diagnostic or therapeutic interventions. In conclusion we established that the presence of a cardiology clinic in the rural areas is reasonable, if their function remains as merely consultative. PMID- 2317248 TI - Peptic ulcer in Puerto Rico. PMID- 2317249 TI - Central Cancer Registry of Puerto Rico, 1973-1982. PMID- 2317250 TI - Trihalomethane levels in Madras public drinking water supply system and its impact on public health. AB - It is known that trihalomethanes (THM) are formed during chlorination of drinking water for disinfection. Heightened concern about these substances is due to the fact that THMs are now characterized as potential mutagen, carcinogen and teratogen. Thus, it is a risk factor in human beings. In the present study, a total number of 13 stations located in different drinking water trunk mains of the city of Madras were analysed for THM using the Gas Liquid Chromatographic method. It is reported that THM are formed after treatment of raw water with chlorine at the levels required for disinfection. The THM level in drinking water increased towards the dead-end of the water trunk mains. A relationship between the distance travelled by the potable water and the level of THM was established. At certain stations, the total trihalomethanes level (TTHM) was found to exceed the EPA's maximum contaminant level. Further, an intermittent addition of the precursors for the formation of THM through the seepage of polluted River Cooum water into the pipe lines has been demonstrated. An experiment on the trihalomethane formation potential (THMFP) clearly revealed the occurrence of higher magnitude of humic substances in source water. Therefore, it is suggested that if suitable steps are not taken, various environmental factors may trigger the THM kinetics. Hence, it is obvious that pretreatment regulations proposed by developed countries are essential if safe drinking water is to be supplied to the people of Madras. PMID- 2317251 TI - [Lead and cadmium content in deciduous incisors of children from Duisburg and Gummersbach--developing trend 1976-1988]. AB - Shed deciduous teeth (incisors only) were collected from children (n = 199) living in Duisburg and Gummersbach (F.R.G.) in 1976 and 1988. The teeth were analysed for lead and cadmium. Considering all teeth, there was a significant of tooth lead and tooth cadmium from 1976 to 1988. The reduction was between -40 and -50% for tooth lead and -45% for tooth cadmium. Regarding tooth lead, the reduction was more pronounced in children from Duisburg, an area heavily polluted by lead and other heavy metals due to the presence of large iron and steel plants and a large lead-/zinc smelter. Teeth from the upper jaw were found to have higher lead and calcium concentrations than teeth from the lower jaw. Moreover, it was found that central incisors had higher lead and cadmium concentrations than lateral incisors. Even after the effects of jaw and tooth type had been allowed for, the reduction of tooth lead and tooth cadmium could be demonstrated. Children living in pre-war houses were found to have higher tooth lead and tooth cadmium levels than children living in post-war houses. The higher lead and cadmium burden of children living in old houses seems to be related to a higher degree of exposure to lead and cadmium via drinking water resulting from the release of these metals from old zinc-plated steel water pipes. In total, our results indicate that there has been a significant decrease of lead and cadmium exposure in West-German children since the mid-70s. The reduction of tooth lead levels parallels the decrease of blood and bone lead levels, which has been observed in previous studies. PMID- 2317252 TI - Drug-DNA interactions. An international conference. 11-15 September 1989, Cambridge, England. Proceedings. PMID- 2317253 TI - A strategy for the construction of double-stranded DNA microcircles with circumferences less than 50 bp. AB - A procedure for the construction of double-stranded DNA microcircles is described that overcomes the natural limits of established circularization procedures. The assembly strategy needs only three components, i.e. two synthetic oligonucleotides containing any sequence of interest and T4 DNA ligase. All components can be provided in large quantities and only two enzymatic reaction steps are required. Such microcircles can serve as a model for topologically fixed and highly bent DNA molecules and the amounts needed for X-ray crystallography, n.m.r. spectroscopy or drug binding studies can readily be produced. The construction of a 42 base pair double-stranded DNA microcircle is presented, by far the smallest double-stranded DNA circle yet described either in vivo or in vitro. PMID- 2317254 TI - Acid-base properties of ellipticine bound to DNA, micelles and liposomes. AB - We have determined the acid-base properties of the alkaloid ellipticine, bound to DNA and to micelles and liposomes, taken as models for membranes, in the prospect of characterizing the actual structure of the bound ligand, this being relevant to the mode of action of the drug. The acid-base properties of ellipticine bound to sonicated calf thymus DNA and SDS micelles are similar as regards their pK values and their dependence on NaCl concentrations. This observation is satisfactorily understood in terms of sodium ion condensation around the negative phosphate and sulphate groups. The slope of pK vs log(Na+) is -1, a value predicted by Friedman theory. The pK of ellipticine bound to cationic (CTAB, DDTAB) or to neutral (Triton X100) micelles and to neutral liposomes (PC) is significantly lower than water (7.4), and, in contrast to the situation in DNA and SDS micelles, does not vary with addition of NaCl. Interestingly, this result is good evidence for ellipticine having a specific pK when bound to a hydrophobic structure. This view is likely to hold for ellipticine bound to DNA. PMID- 2317255 TI - Can cytotoxic activity of anthracyclines be related to DNA damage? AB - Accumulation, cytotoxicity, and DNA damages produced by doxorubicin (DOX), pirarubicin (THP-DOX), fluoro-doxorubicin (ME2303) or its isolated metabolite M1 have been investigated in human myelogenous leukemia cells, sensitive (K562) and resistant to DOX (K562/DOX). These compounds differed by lipophilicity and/or sugar moiety either with (DOX, THP-DOX) or without (ME2303, M1) amino group. In K562 cells, the cytotoxicity was correlated to DNA single-stranded breaks and the intracellular drug amount of DOX or M1. This was not true when the cells were treated with THP-DOX or ME2303. In addition, THP-DOX produced total DNA protein cross-linking. In K562 cells DNA damage was not repaired, while in K562/DOX repair of DNA damage produced by all drugs could be observed. Although in K562/DOX cells drug accumulation was much reduced, higher intracellular drug concentration was required to induce similar level of cytotoxicity and DNA damage. Thus, cytotoxicity produced by anthracycline is not always associated with DNA damage. Different level of resistance to DOX, THP-DOX, ME2303 or M1 is associated with reduced drug accumulation which varies with the structure. PMID- 2317256 TI - Structural analysis of replicating DNA following exposure to cytotoxic drugs: implications for current models of DNA synthesis in mammalian cells. AB - The polynucleotide length of single-stranded regions in double-stranded DNA may be determined by caffeine gradient elution from benzoylated DEAE-cellulose. On the basis of this principle, analysis has been made of sheared, deproteinized DNA isolated from synchronized lymphoblastoid cells. Two classes of single-stranded regions were detected. A minor fraction of replicating DNA contained single stranded regions of 200 nucleotides, whilst the major structural discontinuity involved single-stranded regions of 1-4 kilobases. Newly incorporated [3H]thymidine was principally associated with the latter. Using a 'pulse-chase' protocol, the effect of certain cytotoxic drugs (and related compounds) on the proportion of replicating DNA exhibiting single-stranded character was assessed. The effects were variable. The proportion was increased by hydroxyurea and 3 aminobenzamide, but decreased by inhibitors of DNA polymerase and, to a greater extent, by inhibitors of topoisomerase. Caffeine gradient elution associated drug induced changes with the radiolabelling of long single-stranded regions. The results are consistent with models of DNA replication involving DNA polymerization remote from replicating forks. PMID- 2317257 TI - N-methylmitomycin A cross-linking to nucleosomal structure. AB - The cross-linking reaction of N-methylmitomycin A to 175-bp calf thymus nucleosomes and to reconstituted core particles having known DNA sequences was examined using gel-electrophoresis techniques. The nucleosome structure, as the CAP-DNA complex, leads to a decreased covalent binding in comparison to protein free DNA, suggesting, in addition to sequence specificity, precise geometrical requirements for bifunctional covalent addition of the drug to the nucleic acid. PMID- 2317258 TI - Design of molecules which specifically cleave abasic sites in DNA. PMID- 2317259 TI - Anti-tumour imidazotetrazines. Part XXI. Mitozolomide and temozolomide: probes for the major groove of DNA. AB - The structural and electronic properties of the major groove-binding anti-tumour imidazotetrazinones, mitozolomide and temozolomide were studied using molecular orbital techniques. Structure-activity relationships of mitozolomide derivatives emphasized the importance of a hydrogen bond donor on the C8-substituent and showed that good activity would be expected for derivatives carrying a small C8 substituent with restricted negative potential. The coplanarity of the carboxamide substituent in mitozolomide is unlikely to be disrupted by hydrogen bonding in the major groove. Semi-empirical M.O. calculations gave a very high partial positive charge on C4, indicating an enhanced susceptibility to nucleophilic attack leading to ring opening at this position and the formation of a triazene alkylating agent. PMID- 2317260 TI - Interaction of tetra-azaphenanthrene ruthenium complexes with DNA and oligonucleotides. A photophysical and photochemical investigation. AB - The interaction of complexes Ru(bpy)n(TAP)3-n2+ (1a-1d for n = 0-3) with DNA has been investigated using photophysical methods (emission spectroscopy and laser flash photolysis), by studying the induction of single-strand breaks in plasmid DNA and the formation of adducts using 32P-labelled 27-mer oligonucleotides. Two classes of behaviour are found. Complexes 1a and 1b show quenched emission in the presence of calf thymus DNA and yield photoadducts with the 27-mer, whereas 1c and 1d show enhanced emission and do not form photoadducts. 1a and 1b are more efficient sensitizers for single-strand breaks than are 1c and 1d. It is proposed that the excited states of 1a and 1b, which are stronger oxidizing agents than those of 1c and 1d, are capable of oxidizing guanine. Direct evidence for electron transfer has been obtained from laser flash photolysis of Ru(TAP)3(2+) and dGMP, CT-DNA and polynucleotides. PMID- 2317261 TI - Kinetic and thermodynamic studies on drug-DNA interactions in the ellipticine series. AB - The temperature-jump (T-jump) method has been used to investigate the binding mechanism to calf-thymus DNA of ellipticine and some of its derivatives. The results show that the plant alkaloid, ellipticine, interacts with DNA at a unique intercalation site whereas most of its synthetic derivatives, such as ellipticinium, 9-hydroxy-ellipticinium and related alkyl-oxazolopyridocarbazoles recognize two distinct DNA sites. Parallel analysis of kinetic data and DNA lengthening abilities of these derivatives suggests that only one of these two DNA sites is an intercalation site. Owing to the determination of the genuine number of drug-DNA complexes (inferred from T-jump experiments) and with the results of thermodynamic investigations (Van't Hoff plots), further characterization of the molecular interactions involved in the binding process was proposed. Thus, the formation of the unique intercalation complex of ellipticine was found to be entropy driven whereas binding of drugs which recognize the second class of binding sites was essentially enthalpy driven. These different thermodynamic behaviors suggest that intercalation essentially results from hydrophobic solvent structure effects in contrast to the second binding mode which principally arises from hydrogen bonding interactions through DNA grooves. PMID- 2317262 TI - Bromocriptine produces decreases in cocaine self-administration in the rat. AB - The effect of bromocriptine pretreatment was investigated in rats trained to self administer intravenous cocaine on a fixed-ratio (FR) 5 schedule of reinforcement. Bromocriptine, a dopamine agonist, produced dose-dependent decreases in cocaine self-administration at doses of 4.0, 8.0, 16.0, and 32.0 mg/kg. In a separate group of rats trained on a DRL 20-second schedule of food reinforcement used to produce the same overall rate of responding for food as for cocaine on the FR 5 schedule, bromocriptine did not produce a significant effect on overall response rate, number of reinforced responses, or percent of responses that were reinforced. Given that bromocriptine produced a specific effect on cocaine maintained responding, the present results suggest that bromocriptine is interacting with the neurochemical substrate mediating the reinforcing effects of cocaine. The potential effectiveness of bromocriptine as a pharmacotherapy for cocaine dependence is discussed. PMID- 2317263 TI - Effects of bilateral adrenalectomy on the induction of learned helplessness behavior. AB - In the learned helplessness model of depression, naive Sprague-Dawley rats are exposed to a 40-minute uncontrollable shock training and are subsequently tested in a shock escape paradigm. "Helpless rats" exhibit 11 to 15 failures in a 15 trial test while "nonhelpless" rats and naive controls score 0 to 5 failures in the same test. We report on the effect of bilateral adrenalectomy on the induction of learned helplessness. Most of the adrenalectomized rats (70%) became helpless whereas sham controls responded to the training and testing similarly to naive nonoperated rats (20% to 30% helpless). This increase in behavioral deficits after adrenalectomy was reversed by administration of corticosterone, the naturally occurring glucocorticoid in rat. We conclude that secretion from the adrenal cortex is necessary for the incorporation of a learned response after stress and that a dysregulation of the hypothalamic-pituitary-adrenal axis seems to be involved in helpless behavior. PMID- 2317265 TI - Why we do not know how convulsive therapy works. PMID- 2317264 TI - Subunit characterization and primary structure of bovine adrenal medullary dopamine beta-hydroxylase. AB - Bovine adrenal medullary dopamine beta-hydroxylase was purified by sucrose density sedimentation, gel filtration chromatography, and Concanavalin A Sepharose 4B affinity chromatography. Three subunits have been identified, of 71, 75, and 78 kd, present at a ratio of 1:2:1. Homogeneous subunits were isolated on denaturing polyacrylamide gels. Endoglycosidase treatment reduced each polypeptide to a 66-kd species, indicating that high and complex mannans account for the major differences in the subunits. The subunits and their 66-kd products cross-react with an anti-native dopamine beta-hydroxylase antiserum, suggesting common antigenic epitopes. Amino acid content analysis shows enrichment in glutamic acid/glutamine, aspartic acid/asparagine, glycine, and leucine, with little cysteine, tyrosine, proline, lysine, and methionine. Two to three nonidentical polypeptides have been identified from cyanogen bromide fragments. Comparison of the bovine peptide sequences to the corresponding cDNA-deduced human sequences show substantial similarity. Many of the species-specific differences in the primary structure represent conservative changes in amino acids or single base pair changes in amino acid codons. PMID- 2317267 TI - Heart transplants. PMID- 2317266 TI - [Interpretation of blood gas analysis]. AB - Acid-base problems can be easily identified by the nurse when a systematic approach is utilized during arterial blood gases interpretation. Furthermore, understanding the underlying principles of acid-base balance assist the nurse in choosing the appropriate intervention. By intervening early, many emergency situations can be avoided. Since the nurse is the primary care giver, and is most readily available for the client, early interventions to correct acid-base problems would expedite the client's recovery. This article demonstrates how to identify and explain acid-base problems by answering four key questions. Tables and figures are incorporated to facilitate understanding, and to summarize information in a succinct manner. PMID- 2317268 TI - Toward comprehensive nursing care of the total artificial heart patient. AB - At this time, heart transplantation is the only form of intervention for some end stage cardiac diseases. The use of the artificial heart has been adopted at the Ottawa Institute as a bridge to transplant when a heart is needed, and there are no suitable donors available. The patient is maintained with this technology until a donor heart can be found and transplanted. This article chronicles the steps that were taken by the nursing staff in preparation for these unique patients. The nursing process was the main framework around which we developed our plan of action, assessed and evaluated our interventions and modified nursing care accordingly. The basic functioning of the system that operates the heart is described, as well as nursing care specific to the Total Artificial Heart patient. PMID- 2317269 TI - Structure of 5' regions and expression of phenobarbital-inducible rabbit cytochrome P450IIC genes. AB - To analyze phenobarbital-inducible genes in the P450IIC subfamily, fragments of rabbit genomic DNA containing portions of the P450IIC1 and P450IIC4 genes were isolated and the DNA sequences of the 5'-flanking regions and exons were determined and compared to that of the P450IIC2 gene. The sequences have consensus TATA motifs about 20 bp from the mRNA initiation sites as determined by single-strand nuclease mapping and primer extension. Sequences similar to those for proposed liver-specific regulatory factors, HNF-1 and CCAAT, are found in the P450 5'-flanking regions. A glucocorticoid response element is present in the P450IIC2 gene but is not conserved in P450IIC1 or P450IIC4. Other sequences similar to binding sites for AP-1, the octamer binding proteins, and SPH-1 are present. Except for the TATA motif, none of the potential regulatory sequences was conserved at the same location in the different genes. The P450IIC1 and P450IIC2 genes exhibited high similarity detectable by dot matrix analysis throughout the 700 bp of sequenced 5'-flanking region while the P450IIC4 gene exhibited high similarity to both P450IIC1 and P450IIC2 only for about -150 nucleotides from the RNA initiation site. Southern analysis using probes from the 5' region of the P450IIC4 gene suggests that there are at least three closely related members in the P450IIC4 subgroup in agreement with previous studies. After phenobarbital treatment, levels of P450IIC4 mRNA increased about fourfold, as measured by dot blot hybridization with a P450IIC4-specific oligonucleotide probe or by single-strand nuclease mapping of the 5' end of the mRNA, indicating that the P450IIC4 gene characterized in this study is responsive to phenobarbital. Phenobarbital treatment of rabbits increased in vitro transcription of RNA for both the P450IIC1/2 and P450IIC4 gene subgroups but only slightly and transiently for the constitutive P450IIC3 gene. PMID- 2317270 TI - Structural and regulatory analysis of a cytochrome P450 gene (CYP2C12) expressed predominantly in female rat liver. AB - Cytochrome P450 15 beta is a female-specific gene product that catalyzes the hydroxylation of steroid sulfates at the 15 beta position. Isolation and analysis of the gene for rat P450 15 beta reveals nine coding exons and encompasses more than 35 kb of chromosomal DNA. The intron-exon junctions are at similar positions with the P450 genes of the II family, whose gene structure has been determined. Sequencing of about 2 kb of the 5'-flanking region indicates the presence of the Alu-like R.dre.1 repetitive sequence, a GA-rich stretch that is also found in the 5'-flanking DNA of the male-specific cytochrome P450 16 alpha gene, the enhancer octamer sequence ATGCAAAT, and three CAAAGTT repeats just upstream from the TATA box. Primer extension reveals a major and a minor transcription start site located 22 and 26 bases 5' to the translation initiation codon, respectively. This gene is developmentally regulated and transcriptional activation accounts, at least partly, for the sexually differentiated expression of cytochrome P450 15 beta. PMID- 2317271 TI - Site-directed insertion of long single-stranded DNA fragments into plasmid DNA. AB - A new site-directed method for inserting long single-stranded DNA fragments into any region of a duplex vector is described. Its major advantage is independence of the location of the restriction sites. The method involves the assembly of single-stranded DNA fragments by ligation to both ends of the inserted fragments of two cohesive flanks that are complementary to the target region. Short oligonucleotide templates are used to direct the ligation. The resulting fragments, designated further as omega fragments with cohesive flanks, are hybridized with a gapped DNA vector. The heteroduplexes are transformed into Escherichia coli cells without enzymatic filling and sealing of gapped DNA. As a consequence of intracellular repair and heteroduplex resolution, insertion mutants are recovered. To demonstrate the method's efficiency, we inserted a 51 nucleotide synthetic DNA fragment containing a modified glucocorticoid receptor binding site into the region of pBR322, near the transcription starting point of the tet gene. The method we developed makes possible site-directed insertion of synthetic and genome-derived DNA fragments at least 200 nucleotides long. PMID- 2317272 TI - Reflex facilitation of the rabbit nictitating membrane response by an auditory stimulus as a function of interstimulus interval. AB - The ability of an auditory stimulus to facilitate the amplitude and latency of the unconditioned nictitating membrane (NM) response in rabbits was investigated over a wide range of interstimulus intervals (ISIs) for both delay (Experiments 1 4) and trace (Experiments 3 and 4) procedures. The auditory stimulus was a 1000 Hz tone (T) at either 85 or 95 dB, and the reflex-eliciting stimulus was a 2.0 psi (pounds per square inch) corneal air puff (AP). The results indicate that (a) robust facilitation of the NM response, as measured by an increased amplitude and a reduced latency, can be obtained at long ISIs (2,000-32,000 ms); (b) increasing the tone intensity can increase reflex facilitation of the peak amplitude; (c) at comparable ISIs, delay procedures produce more facilitation of both amplitude and latency than do trace procedures; and (d) when trace procedures are used, amplitude and latency facilitation by a 125-ms tone follows an inverted U-shaped ISI function in which facilitation peaks between 125 and 500 ms, rapidly decreases between 1,000 and 2,000 ms, and disappears by 4,000 ms. PMID- 2317273 TI - Behavioral and neuroanatomical effects of prenatal, postnatal, or combined exposure to ethanol in weanling rats. AB - Separate and combined effects of prenatal and postnatal exposure to ethanol on activity, emotionality, learning, and hippocampal neuroanatomy were examined in infant rats. Neonatal rats from mothers that were fed either a liquid ethanol (E) or control (C) diet on Gestational Days (G) 1-21 were artificially reared during Postnatal Days (P) 4-12 on either 3% ethanol (E) or isocaloric maltose/dextrin (C) in a milk formula. Pups in these treatment groups (EE, EC, CE, and CC) were tested for activity and emotionally in an open field on P19, for acquisition and extinction of an appetitive, straight runaway task on P20-P21, and for the effects of ethanol treatments on alterations in hippocampal neuroanatomy on P21. Differences in activity and emotionally were slight. Ethanol affected both the partial reinforcement acquisition effect and the partial reinforcement extinction effect. Hippocampal cell density (compared with Group CC) showed a 12% reduction in CA1 pyramidal cells and an 11% reduction in mature granule cells in Groups EC and EE; the CA4 area (compared with Group CC) was significantly larger after postnatal exposure (Groups CE and EE). Significant positive correlations were found between rate of extinction after partial reinforcement (PRF) training and CA1 pyramidal cell density in Groups CC and CE. A significant negative correlation was found between extinction rate after PRF training and CA4 area in Group EE. PMID- 2317274 TI - Effects of dl-fenfluramine on dextrin and casein intakes influenced by textural preferences. AB - The effects of dl-fenfluramine (2.5 mg/kg) on selection between the textures of nutrient preparations were tested by presenting rats with a choice between pairs of three sizes of chow crumb with 45% dextrin, casein, maltodextrin, or calcium caseinate added or with no nutrient added. The usual effect of fenfluramine was to reduce the intake preference for a coarser over a finer crumb. This drug effect differed, however, with the preparation of protein or of carbohydrate added to each crumb size. There was no consistent effect of nutrient, and hence the reported effects of this dose of dl-fenfluramine cannot be attributed to nutrient-specific selection. PMID- 2317276 TI - Prenatal and neonatal testosterone exposure interact to affect differentiation of sexual behavior and partner preference in female ferrets. AB - Implanting testosterone (T) subcutaneously over Postnatal Days 5-20 masculinized sexual behavior, reduced proceptive responsiveness, and shifted sexual preference more readily in male than in female ferrets gonadectomized on Day 5. This enhanced sensitivity of males to neonatal T was best duplicated in females exposed transplacentally to T over Embryonic Days (E) 27-39 (41-day gestation) and injected at birth with T (2.5 micrograms sc in oil: 10% ethanol). Extended exposure of male ferrets to high levels of T, beginning shortly after the onset of testicular steroidogenesis (E25) and continuing for several hours after birth (E41) normally sensitizes their brains to the subsequent organizational effects on coital performance and sexual motivation of the relatively low levels of T that circulate in male ferrets during the first 3 postnatal weeks. PMID- 2317275 TI - Dependence of adrenalectomy-induced sodium appetite on the action of angiotensin II in the brain of the rat. AB - Adrenalectomized rats express a robust sodium appetite that is accompanied by high levels of blood-borne angiotensin II and is caused by angiotensin II of cerebral origin. Blood-borne angiotensin II is elevated in rats consuming NaCl after adrenalectomy, and plasma angiotensin II concentrations are increased further when the animals cannot drink a NaCl solution. These phenomena are the result of the pathological removal of aldosterone, because replacement therapy returned both sodium intake and plasma angiotensin II concentrations to preadrenalectomy levels. The adrenalectomized rat's appetite for sodium is completely suppressed by interference with the central, but not the peripheral, action of angiotensin II. These data demonstrate that the mechanism of the sodium appetite of the adrenalectomized rat is a pathological instance of the angiotensin/aldosterone synergy that governs the sodium appetite of the adrenal intact, sodium-depleted rat. Because aldosterone has been removed, angiotensin acts alone to produce the appetite. Furthermore, the data show that it is angiotensin II of central origin that is important for sodium appetite expression. PMID- 2317277 TI - Cholecystokinin conditioning in rats: ontogenetic determinants. AB - Low doses (0.12-2.0 micrograms/kg) of cholecystokinin octapeptide (CCK), administered intraperitoneally, support the formation of conditioned odor preference in neonatal and weanling rats. Exposure to a novel odor was paired with CCK injection, and the rats' olfactory choices were assessed 24 hr later. Rats at 5, 11, and 22 days of age preferred the odor previously associated with CCK, compared with vehicle-injected littermates. In contrast, CCK failed to support olfactory conditioning in 28-day-old rats, whether they were (a) weaned and independently housed, (b) residing with the dam and suckling, or (c) fed only milk. Adult rats also did not establish an odor preference with CCK as the unconditioned stimulus. Thus, CCK's changing impact from positive to neutral probably occurs during the rats' 4th postnatal week and may be related to maturational changes occurring during the final stages of weaning. PMID- 2317278 TI - An associative process maintains reflex facilitation of the unconditioned nictitating membrane response during the early stages of training. AB - The presentation of a neutral or conditioned stimulus (CS) at an appropriate interval prior to the presentation of a corneal airpuff, or a paraorbital shock (unconditioned stimulus, US) can facilitate the amplitude of the unconditioned nictitating membrane (NM) response in rabbit. In two experiments, it was demonstrated that an associative process mediates the maintenance of that facilitation during repeated CS-US pairings. Although CS-alone presentations produced a substantial decrease in the amount of reflex facilitation in animals not pretrained with the CS, pretraining that consisted of paired CS-US presentations prevented that decrease when CS-alone presentations were subsequently given. Conditioned facilitation of the unconditioned response occurred very rapidly (within 5-12 trials in these experiments) and long before the appearance of overt conditioned responses to the CS. In addition, it was demonstrated that conditioned facilitation can be relatively specific to the tonal frequency of the CS. These results indicate the first sign of conditioning of the NM response is exhibited in the amplitude of the unconditioned response. PMID- 2317280 TI - dl-fenfluramine challenge to nutrient-specific textural preference conditioned by concurrent presentation of two diets. AB - Effects of the ingestion of protein and carbohydrate conditioned a preference for one size of chow particle over another, which was triggered by need for a specific nutrient. This learned elicitation of nutrient-specific dietary selection was not changed by injection of dl-fenfluramine HCl (2.5 mg/kg). This indicates that previously observed effects of fenfluramine on differential intakes of dextrin- and casein-rich diets do not depend on nutrient-specific self selection. PMID- 2317279 TI - Effects of systemic atropine sulfate administration on the frequency content of the cat sensorimotor EEG during sleep and waking. AB - Sensorimotor electroencephalogram (EEG) frequencies in cats were evaluated with power spectral analysis before and after 3 doses of atropine sulfate. All doses of atropine tested caused enhanced EEG slow waves (0-7 Hz) and spindles (8-15 Hz) during waking immobility, and postdrug frequency profiles during slow-wave sleep and waking immobility were identical. With 0.75 mg/kg atropine, movement (head movement, locomotion) resulted in EEG desynchronization and reduced power in all frequencies less than 24 Hz. After 1.5 or 3.0 mg/kg atropine, power in low frequencies remained elevated during movement, but power in spindle frequencies was significantly reduced compared with other states. During active REM sleep after 1.5 mg/kg atropine, power in spindle frequencies was significantly lower than that during quiet REM sleep. These results indicate that the sensorimotor cortical EEG in cats is under the control of multiple systems. At least 1 of these systems is active during movement, and its actions are resistant to muscarinic receptor blockade. PMID- 2317281 TI - Spatial contiguity, not cue-to-consequence, is the issue in taste-potentiated noise-illness associations: comment on Holder, Bermudez-Rattoni, and Garcia (1988). AB - Holder, Bermudez-Rattoni, and Garcia (1988) allege to have failed to corroborate findings from our laboratory (Ellins, Cramer, & Whitmore, 1985; Ellins & von Kluge, 1987) that taste-potentiated noise-illness associations can be established under conditions of spatial contiguity. We maintain that Holder et al. have provided additional experimental support for our contention that spatial contiguity is an important factor in the taste-potentiation of nongustatory stimuli. In addition, we take issue with their conclusion that the results of our research are incompatible with the conditioning principle of cue-to-consequence. PMID- 2317282 TI - The conditioned stimulus-unconditioned stimulus-feedback feeding sequence: reply to Ellins, von Kluge, and Cramer (1990). AB - Taste-potentiated noise aversions have been demonstrated in rats (Ellins, Cramer, & Whitmore, 1985; Ellins & von Kluge, 1987; Holder, Bermudez-Rattoni, & Garcia, 1988). However, these aversions are apparently less readily established than taste-potentiated odor aversions suggesting that all exteroceptive stimuli are not equally well potentiated by taste (Holder et al., 1988). Despite the claims of Ellins, von Kluge, and Cramer (1990), we replicated their findings and see no inconsistency between our findings and theirs. Both sets of results are explained by a common theory of conditioning (Garcia, 1989; Garcia & Holder, 1985). PMID- 2317283 TI - Increased immobility in an automated forced swimming test following lesion of the habenula in rats: absence of evidence for a contribution from motor impairment. AB - The effects of lesions of the habenula on responses during a forced swimming test (FST) were examined. Active behavior, documented by turns on a drum immersed in a water tank, were reduced in lesioned rats. Lesioned rats also demonstrated an inability to escape from the water by climbing onto the drum when it was locked in position at the end of the test. There was a tendency for lesioned rats to show more activity in open-field tests either after the FST or independent of such prior testing. Lesioned rats showed no motor or postural abnormalities and were able to maintain position for longer than controls during a rotating rod test. Collectively, the results are compatible with the suggestion that lesions of the habenula impair the ability to change motor strategies under stress but indicate such failures may not be ascribed to gross motor impairment. PMID- 2317285 TI - State-dependent fear extinction with two benzodiazepine tranquilizers. AB - Four experiments with rats were run to investigate whether fear extinction conducted under the influence of a benzodiazepine transfers to the undrugged state. Fear was conditioned by pairing an experimental chamber with footshock and was assessed by observing freezing, a characteristic response of the rat to stimuli associated with shock. In Experiment 1, extinction of the chamber cues under chlordiazepoxide (librium) or diazepam (valium) was compared with extinction under a placebo; both drugs interfered with extinction in a dose dependent manner as indicated by freezing during an undrugged test. Further results with chlordiazepoxide suggested that the effect depended on the drug's specific combination with extinction and that it occurred even though the extinction procedure otherwise eliminated fear completely (Experiment 2). Repeated preexposure to the drug, and the development of partial tolerance to its sedative effects, did not weaken the interference effect (Experiment 3). Other evidence suggested that the drug signaled or retrieved extinction instead of disrupting learning or consolidation (Experiment 4). The results are consistent with research suggesting that extinguished fear can be "renewed" if the exteroceptive contextual stimuli are changed after extinction. Extinction combined with either unique exteroceptive or interoceptive cues may be specific to its context. PMID- 2317284 TI - Electrical stimulation of brainstem nuclei: elicitation, modification, and conditioning of the rabbit nictitating membrane response. AB - Electrical stimulation of the reticular formation, pars oralis of the spinal trigeminal, abducens, and accessory abducens nuclei was used to assess the role of these sites in the elicitation, reflex modification, and classical conditioning of the rabbit's nictitating membrane response (NMR). Although electrical brain stimulation of the targeted sites revealed comparable levels of unconditioned responses, the spinal trigeminal nucleus was the only site at which reflex modification and conditioned response acquisition occurred reliably. These findings suggest that a locus of conditioned stimulus and unconditioned stimulus interaction, mediating either or both reflex modification and NMR conditioning, is on the sensory side of the reflex arc, at the pars oralis of the spinal trigeminal nucleus. PMID- 2317286 TI - Diazepam's impact on self-stimulation but not stimulation-escape suggests hedonic modulation. AB - In rats that self-administered lateral hypothalamic (LH) stimulation through chronically implanted electrodes, ip diazepam (DZ) increased rates and decreased thresholds of self-stimulation (SS) in a dose-related manner. Stimulation-escape (SE), however, was refractory to the drug. There was a complete dichotomy in electrode placements along the anterior/posterior plane. Every pure-reward electrode location was posterior to every reward-escape electrode. DZ-sensitive SS appears to be mediated by a reward substrate common to both pure-reward and reward-escape rats, whereas SE is supported by an aversive system unaffected by DZ and stimulated only in those rats with anterior placements. The lack of control over SE suggests that the drug's effect on stimulation-induced conduct is to increase reward rather than to decrease aversion. This hypothesis is discussed in the context of DZ's interactions with drugs of abuse. PMID- 2317287 TI - Visual response latencies in temporal lobe structures as a function of stimulus information load. AB - In a monkey performing a visual delayed matching-to-sample task, units and visual evoked potentials (VEPs) were sampled from the inferior bank of the superior temporal sulcus (STS; Areas TEa and IPa), the hippocampus, and the presubiculum. VEP latencies indicated that flash information--signaling the imminent presentation of a color sample to be retained--reached the presubiculum and the hippocampus substantially earlier than the STS. In contrast, color sample VEP latencies did not differ between sites, arriving at all sites appreciably later than flash VEPs. Unit data indicated generally excitatory responses to both stimuli at all sites and net inhibition during the interstimulus interval separating flash from sample. As with VEPs, unit latencies to flash were shorter than to sample stimuli. The alerting flash data imply activation of the hippocampus occurring before activation of the STS cortex, whereas the coincident arrival of color sample information suggests temporal synchronization between these structures. PMID- 2317288 TI - Organizational effects of early gonadal secretions on sexual differentiation in spatial memory. AB - Neonatally castrated (MNC) and control male rats (MC) and female rats treated neonatally with estradiol benzoate (FNE) and female controls (FC) were studied. In Exp. 1 spatial memory was assessed using a 12-arm radial maze. During acquisition, MC and FNE groups were more accurate in choice behavior than FC and MNC groups. In Exp. 2 the discriminative control exerted by different types of cues was evaluated. Alteration of the geometry of the room but not movable landmarks disrupted performance of MC and FNE groups. For the FC and MNC groups, alteration of either geometry or landmarks did not disrupt performance. In Exp. 3 the effect of a 15-min delay was determined. MC and FNE groups were more disrupted by a delay than MNC and FC groups. Together, these data suggest that early exposure to gonadal steroids (probably estradiol) improves acquisition of spatial tasks by reorganizing and simplifying associational-perceptual processes that guide spatial ability. PMID- 2317290 TI - Aging and qualitative characteristics of memories for perceived and imagined complex events. AB - Older and younger adults' memory for perceived and imagined events was examined with a procedure in which everyday situations are simulated in the laboratory. Subjects perceived some situations and imagined others. Later, they were asked to rate their memory for various aspects of these situations (e.g., amount of perceptual detail, thoughts and feelings). A recall test followed the ratings. On the rating scale, for both perceived and imagined events, older subjects reported better memory for their thoughts and feelings than did younger subjects. In addition, on the recall test, older subjects produced more thoughts and feelings than did younger subjects, whereas younger subjects produced more perceptual and spatial information. These results suggest that older subjects may not inhibit personal information (e.g., thoughts and feelings), and this information may interfere with memory for other aspects of information, such as perceptual and contextual details (Hasher & Zacks, 1988). PMID- 2317289 TI - Depressive symptom patterns among older women. AB - The structure of depressive symptom patterns was investigated in a community sample of 344 women between the ages of 51 and 92 who were administered the SCL 90-R Depression and Additional Symptoms Scales. Confirmatory factor analysis was used to test alternative measurement hypotheses implied by clinical formulations of depressive symptom patterns among elderly persons. The findings show support for the hypothesis that 2 somewhat different depressive syndromes, along with 4 more delimited forms of distress, underlie symptom-reporting patterns. Implications of these findings for future research on the relation between aging and depression are discussed. PMID- 2317291 TI - Reliability of proxy response on mental health indices for aged, community dwelling women. AB - The correspondence between respondent and proxy response was evaluated on 4 mental health measures (Affect Balance Scale, Center for Epidemiological Studies Depression Scale, Mental Status Questionnaire, and Mini-Mental State Examination) with a sample of 538 respondent-proxy pairs. Results indicated that respondent and proxy responses were strongly associated, particularly for the cognitive measures. This association was found even for respondents classified as depressed or cognitively impaired. Although there was evidence of proxy bias, with proxies underrating affective status and overrating cognitive status, the magnitude of the bias proved small for all scales but the Mental Status Questionnaire. Examination of response comparability by proxy characteristics showed that choice of proxy affected agreement and bias. Implications of these findings for survey research are discussed. PMID- 2317292 TI - Learning mnemonics: roles of aging and subtle cognitive impairment. AB - Previously validated methods of memory training were used in conjunction with the Folstein Mini-Mental State Examination (MMSE) to explore the relationship between complexity of learned mnemonic, aging, and subtle cognitive impairment. Subjects were 218 community-dwelling elderly. Treatment included imagery mnemonics for remembering names and faces and lists. There was a significant interaction among age, type of learning task (face-name vs. list), and improvement when controlling for MMSE score. There was also a significant interaction among MMSE score, type of learning task, and improvement when controlling for age. Scores on the more complex list-learning mnemonic were more affected by age and MMSE scores than were scores on the face-name mnemonic. Implications of the findings for cognitive training of the old old and the impaired are discussed. PMID- 2317293 TI - The nature and basis of age-related changes in dynamic visual acuity. AB - The ability of observers to resolve moving targets, or dynamic visual acuity (DVA), was determined for a group of young adults (M age = 19.6 years) and a group of older adults (M age = 67.6 years). Targets were presented at two luminance levels over a range of velocities (30, 60, 90, and 120 deg/s) and at 2 durations (200 and 600 ms). The younger subjects exhibited superior DVA under nearly all conditions, but this effect was essentially eliminated by the luminance adjustment. These results are interpreted in terms of decreased retinal illumination in the older subjects rather than in terms of age-related changes in the underlying eye movement systems. Practical and theoretical implications are discussed. PMID- 2317294 TI - Training effects on Raven's progressive matrices in young, middle-aged, and elderly adults. AB - Previous training studies of fluid intellectual abilities have involved training on either figural relations or induction tasks. In the present study, young, middle-aged, and elderly adults were given training on another measure of fluid ability--Raven's Progressive Matrices. The training involved a strategy-modeling technique that lasted no more than a few minutes. The results indicated that (a) performance on the Raven decreased with increasing age, (b) training significantly improved performance, and (c) the effect of training did not differ as a function of the age or sex of the subjects. Thus, the results indicate that performance on the Raven can be significantly improved in a single, brief training session. PMID- 2317295 TI - Two-dimensional grid is ineffective against demented patients' exiting through glass doors. AB - An extension of the visual-grid method of controlling egress from a 30-bed specialized dementia care unit of a nursing home was tested. Hussian and Brown (1987) significantly reduced patient egress attempts from a state hospital psychogeriatric ward with strips of beige tape on a brown floor near an opaque door. In this study, black tape was used on a white floor at both glass exit doors, in the same configuration as Hussian and Brown's (1987) most effective condition. Data indicated no intervention effect. Results are attributed mainly to the glass doors, which allow an outdoor view and can entice residents outward and distract them from the floor grid. PMID- 2317296 TI - Relations between source amnesia and frontal lobe functioning in older adults. AB - A study is reported in which the relations among normal aging, source amnesia, and frontal lobe functioning were explored. Twenty-four older adults (aged 60-84 years) were tested on their ability to remember where they had acquired new factual information; they were also given the Wisconsin Card Sorting Test (WCST), a test of verbal fluency, and other psychometric tests. The degree of source amnesia in this normal sample correlated with age, verbal fluency, and some measures from the WCST. Source amnesia was not related to Performance IQ, however, or to a measure of fact recall. The implications for the relations among aging, memory, and frontal lobe functions are discussed. PMID- 2317297 TI - Systematic 24-hr behavioral observations of sleep and wakefulness in a skilled care nursing facility. AB - Sleep patterns of aged, infirm, demented, chronically institutionalized residents of a skilled-care nursing facility were studied. The purpose of this naturalistic study was to describe sleep and wakefulness (S/W) within the limits afforded by brief behavioral observations and to examine homeostasis and diurnal rhythmicity of S/W as a function of psychoactive drug intake. Observers noted S/W every 15 min, 24 hr a day for 10 days in 24 Ss. Results indicated substantial individual variation in daytime hours. Daily and weekly variation within Ss was minimal. Sleep was least likely near sunset. Ss on psychoactive drugs showed dampened diurnal variation in S/W rhythms. In Ss not on such drugs, there was a suggestion of homeostasis of S/W between sleep during the morning and evening hours. Results are discussed methodologically (viability of approach), theoretically (age related change in sleep), and practically (potential treatments). PMID- 2317298 TI - Genetic influence on life events during the last half of the life span. AB - Genetic influence on perceptions of major events later in life was assessed with a combination of twin and adoption designs as part of the Swedish Adoption/Twin Study of Aging (SATSA). The SATSA design includes 4 groups totaling 399 pairs of same-sex twins: identical and fraternal twins reared apart and matched twins reared together. The average age of the twins was 59 years. The results demonstrate significant genetic influence on reports of the occurrence of life events, especially for controllable events in which the individual can play an active role. Maximum likelihood model-fitting estimates of genetic influence indicate that 40% of the variance of the total life events score is due to genetic differences among individuals. How genetic factors can affect life experiences and directions for future research are discussed. PMID- 2317299 TI - Dementia and agitation in nursing home residents: how are they related? AB - The link between agitated behaviors and cognitive functioning in 408 nursing home residents was examined. Results showed that cognitively impaired residents manifested aggressive behaviors (e.g., cursing, hitting) and physically nonaggressive behaviors (e.g., pacing). The highest levels of physically nonaggressive behaviors were manifested by those residents who presented intermediate levels of impairment in their performance of activities of daily living. Cognitively intact residents exhibited verbally agitated behaviors (e.g., complaining). These findings have important implications for caregivers of agitated nursing home residents. PMID- 2317300 TI - Differences in social support among retirees and workers: findings from the Normative Aging Study. AB - Cross-sectional differences between retirees and workers in the importance of coworkers as a source of support, as well as in general quantitative support (social networks and frequency of interaction) and qualitative support (confidants and the perceived reliability of support) were examined. The sample consisted of 1,513 older men (mean age = 61), participants in the Normative Aging Study. Half (56%) were working, and the rest were retired. Slightly fewer retirees than workers reported coworker friends, especially among those who were long-term retirees or who did not work at all in retirement. Whereas similar findings were seen with quantitative support, workers and retirees reported nearly identical levels of qualitative support. However, retirees almost never discussed personal problems with former coworkers. The relevance of these findings for the convoy construct is discussed. PMID- 2317301 TI - A self-rating scale for evaluating memory in everyday life. AB - A memory self-rating scale is described that includes 21 ability-to-remember items, 24 items assessing frequency of occurrence of memory failures, and 4 global rating items assessing overall comparison to others, comparison to the best one's memory has ever been, speed of recall, and concern or worry over memory function. Factor analysis yielded 5 orthogonal Ability to Remember and 5 orthogonal Frequency of Occurrence factors. The factor structure was not affected by age or sex, and level of complaint on the factor scores was not strongly associated with age. PMID- 2317302 TI - Tenacious goal pursuit and flexible goal adjustment: explication and age-related analysis of assimilative and accommodative strategies of coping. AB - Crises and critical life transitions activate 2 distinct but complementary modes of coping, (a) transforming developmental circumstances in accordance with personal preferences (assimilative tendency) and (b) adjusting personal preferences to situational constraints (accommodative tendency). Assimilative and accommodative tendencies were measured by a questionnaire comprising 2 independent scales (Tenacious Goal Pursuit and Flexible Goal Adjustment). Both scales predict high life satisfaction and low depression and are positively related to generalized internal control beliefs. The scales evinced an opposite relation to age: Cross-sectional analyses on a sample of 890 Ss in the age range from 34 to 63 years revealed a gradual shift from an assimilative to an accommodative mode of coping. Implications for theories of depression and successful aging are discussed. PMID- 2317303 TI - On-line processing of written text by younger and older adults. AB - Word-by-word reading times were measured for young and elderly adults who read single sentences for immediate recall. The reading strategies of young and old were similar in that both groups allocated time to process word-level and constituent-level features. Young and elderly readers differed mainly in how they allocated time for organizational processing: Whereas younger adults allocated extra processing time at sentence boundaries as well as at major and minor clause boundaries, older adults allocated extra time at major and minor clause boundaries only. Results were generally consistent with the notions that processes that are more microlevel (e.g., word access) become automatic with practice and that age deficits are minimal for such processes. Age differences in organization time allocated at clause boundaries, however, suggested age-related limitations in working memory processing. PMID- 2317304 TI - Developmental assumptions in literary criticism and their implications for conceptions of continuity and change in literary creativity. AB - With 2 critical readings of William Wordsworth's "Ode: Intimations of Immortality From Recollections of Early Childhood," this article presents contrasting assumptions of the literary critic about the development of artistic creativity and relates them to the issue of continuity and change in literary expression over the life span. The unveiled assumptions parallel the "hard" (structuralist) and "soft" (life-span) conceptions of human development prevailing in contemporary psychology. A better understanding of creative development may be reached by superimposing the principles derived from the soft metatheoretical orientation on those of the hard theory. PMID- 2317305 TI - Worker equality and adult development: the kibbutz as a developmental model. AB - Adults' social status, particularly their occupations, is a powerful predictor of their level of moral and ego development. This association's inevitability was tested by examining the relationship of personal development with social status among 3 groups of workers. Results showed that kibbutz workers' moral and ego development were not significantly associated with educational, occupational, or social class standing, but that Israeli city and North American workers' moral and ego development were significantly associated with all measures of social status. In further contrast, work complexity was significantly associated with both moral and ego development only for kibbutz workers, suggesting that they engage in jobs that are appropriate to their psychological development without creating social inequality. Implications for developmental theory and workplace research are considered. PMID- 2317306 TI - Memory factors in age-related differences in simple reasoning. AB - Adults in their 50s were compared with adults in their late teens or 20s in the accuracy of relatively simple reasoning decisions involving varying amounts of information. Because the magnitude of the age differences in decision accuracy was independent of the amount of information relevant to the decision, it was suggested that adults in their 20s and 50s do not differ in the effectiveness of integrating information across multiple premises. However, the 2 groups differed in the accuracy of trials involving only a single relevant premise, and thus it was inferred that 1 factor contributing to reasoning differences within the age range from 20 to 60 may be a failure to encode, or retain, relevant information. PMID- 2317307 TI - Differences in abstraction ability with age. AB - Three tests of abstraction were administered to 89 optimally healthy subjects aged 30-79. Performance on all 3 tasks showed significant differences with age. This was primarily, although not entirely, the result of deficits in performance by the 70-year-old subjects. These results do not appear to be related to changes in memory ability or to a differential increase in a particular type of abstraction error. PMID- 2317309 TI - Suicidal attempts with zidovudine. PMID- 2317310 TI - HIV infection and histiocytosis X. PMID- 2317308 TI - Reducing the spread of HIV infection in sub-Saharan Africa: some demographic and economic implications. AB - Any reduction in the rate of spread of HIV infection has consequences for the incidence and demographic effects of AIDS. In this paper, output from a published mathematical model of the dynamics of HIV transmission through heterosexual contact is used to study the implications of reducing HIV transmission on demographic patterns and national health budgets in sub-Saharan Africa. The major conclusion is that both the timing and the effectiveness of reducing HIV transmission are non-linearly related to their potential demographic and economic effects. The analysis emphasizes the benefits to be gained from a concerted effort to reduce the spread of HIV infection as early as possible in the time course of the epidemic. PMID- 2317311 TI - Recovery of HIV antibodies in eluates from plasma and erythrocytes dried on filter paper and stored under various conditions. PMID- 2317312 TI - HIV infection and squamous cell carcinoma of sun-exposed skin. PMID- 2317313 TI - Thrombolytic therapy in the peripheral circulation. PMID- 2317314 TI - Improve nursing's image: alleviate the nursing shortage. PMID- 2317316 TI - Morphometry of the parahippocampal gyrus in schizophrenics and controls. Some anatomical considerations. AB - Volumetry of the parahippocampal gyrus was performed applying stereological methods. No difference was found comparing 18 schizophrenic brains with 18 sex- and age-matched controls. Variable sulcal pattern may contribute to inconsistency with previous findings. PMID- 2317315 TI - Some central pharmacological effects of (+)- and (-)-oxaprotiline. AB - The central action of oxaprotiline (OXA) enantiomers, administered in a single dose, was studied in rats and mice. (+)-OXA and (-)-OXA attenuated reserpine- and apomorphine-induced hypothermia [(+)-OXA in a more potent manner] in mice and reduced the immobility time in the behavioural despair test in rats. Both OXA enantiomers inhibited locomotor activity in mice and rats, and enhanced and prolonged amphetamine- and apomorphine-induced stereotypy in rats. (-)-OXA potentiated the amphetamine hyperactivity in rats, but not in mice. Nomifensine hyperactivity in rats was unaffected by either enantiomer, and locomotor hypoactivity induced by low doses of apomorphine was also unchanged, as was L DOPA-induced locomotor hyperactivity in mice. Apomorphine-induced climbing in mice was attenuated by (+)-OXA. Clonidine locomotor hypoactivity and hypothermia were unchanged, and clonidine-induced aggressiveness was attenuated by (+)-OXA. Neither OXA enantiomer affected the action of oxotremorine. In some tests the effect of OXA was stronger at 3 h than at 1 h after administration. The above results indicate that both OXA enantiomers--in particular (-)-OXA--increase some dopaminergic behavioural effects in rats. PMID- 2317317 TI - 5-HT1A receptor function in depression: effect of chronic amitriptyline treatment. AB - Hypothermic responses to 5-HT1A receptor activation by the selective ligand ipsapirone (IPS) were attenuated in depressed patients as compared to controls. Chronic treatment with amitriptyline (AMI) further impaired 5-HT1A-mediated hypothermia. The results indicate a subsensitive (presynaptic) 5-HT1A receptor and/or a defective post-receptor signalling pathway in depression and are consistent with the hypothesis that 5-HT1A receptors are down-regulated during AMI treatment. PMID- 2317318 TI - Oculoplastic surgery. PMID- 2317319 TI - Fretting over fragmentation. The debate continues. PMID- 2317320 TI - Expanding interspecialty cooperation. PMID- 2317321 TI - The incidence of aminoglycoside antibiotic-induced hearing loss. AB - The definition of ototoxicity in most clinical studies of aminoglycoside antibiotics is an increase in pure-tone threshold from a baseline audiogram greater than or equal to 15 dB at two or more frequencies, or greater than or equal to 20 dB at one or more frequencies. In this study, test-retest auditory threshold differences of this magnitude were found in a group of 20 normal volunteers who were not taking any known ototoxic drugs. Depending on which of the two criteria for ototoxicity are used, these data represent a 20% or 33% incidence of ototoxicity. We believe that many of the audiometric changes reported to represent aminoglycoside antibiotic ototoxicity may actually represent the normal test-retest variability of pure-tone audiometry. If this is true, the reported incidence of hearing loss due to aminoglycoside antibiotics may be exaggerated. PMID- 2317322 TI - An estimate of the prevalence of tinnitus caused by spontaneous otoacoustic emissions. AB - Prototypical experimental tests for linking spontaneous otoacoustic emissions with disruptive tinnitus have been described previously. Using similar experimental tests on 96 tinnitus sufferers, an estimate is made here of the prevalence of tinnitus caused by spontaneous otoacoustic emissions: the 95% confidence limits of this estimate are 1.11% and 9.05%. PMID- 2317323 TI - The development of the Dizziness Handicap Inventory. AB - Conventional vestibulometric techniques are inadequate for quantifying the impact of dizziness on everyday life. The 25-item Dizziness Handicap Inventory (DHI) was developed to evaluate the self-perceived handicapping effects imposed by vestibular system disease. The development of the preliminary (37 items) and final versions (25 items) of the DHI are described. The items were subgrouped into three content domains representing functional, emotional, and physical aspects of dizziness and unsteadiness. Cronbach's alpha coefficient was employed to measure reliability based on consistency of the preliminary version. The final version of the DHI was administered to 106 consecutive patients and demonstrated good internal consistency reliability. With the exception of the physical subscale, the mean values for DHI scale scores increased significantly with increases in the frequency of dizziness episodes. Test-retest reliability was high. PMID- 2317324 TI - Rhabdomyosarcoma of the head and neck in children. AB - Rhabdomyosarcoma is the most common soft-tissue sarcoma in infants and children, with the head and neck being the most frequent site of involvement. Treatment for this neoplasm has undergone many changes, with a much improved prognosis using a combination of surgery, radiation therapy, and chemotherapy. This retrospective analysis presents the management and outcome of 60 children (aged 3 months to 18 years) with rhabdomyosarcoma of the head and neck evaluated at the Children's Hospital of Philadelphia (Pa) between 1970 and 1987. The overall death rate for all head and neck sites decreased from 50% in 1970 to 1979 to 23% in 1980 to 1987, reflecting the improved management protocol. PMID- 2317325 TI - Patterns of cervical node metastases from squamous carcinoma of the larynx. AB - We undertook a retrospective review of 247 previously untreated consecutive patients from 1965 to 1986 with primary squamous cell carcinoma of the supraglottic or glottic larynx to ascertain the prevalence of neck node metastases by neck level. The 247 patients underwent a total of 262 radical neck dissections. Patients were grouped by clinical neck status at the time of neck dissection: elective dissection in the NO neck; immediate therapeutic dissection in the N+ neck; and subsequent therapeutic dissection in the NO neck that over time converted clinically to N+. Detailed analysis revealed a predominance of neck node metastases in levels II, III, and IV for all clinical neck groups. Level V was rarely involved, but always in conjunction with neck node metastases in levels II, III, or IV (ie, N2 disease). Level I was rarely involved; involvement occurred with neck node metastases in levels II, III, or IV 75% of the time. Level I involvement correlated with T3 or T4 primary tumors exhibiting histologic extralaryngeal spread. These data support the trend toward selective limited neck dissection in both NO and N1 patients. PMID- 2317327 TI - Carotid body paragangliomas. A clinicopathologic and DNA analysis of 13 tumors. AB - The clinical and pathological features of 13 carotid body paragangliomas from 12 patients were examined and correlated with the DNA ploidy pattern as determined by image analysis. These tumors occurred in 7 women and 5 men aged 19 to 62 years (average, 42 years). All presented with a slowly enlarging, usually asymptomatic mass of 2 weeks' to 25 years' duration. Two patients were related and had a family history of paragangliomas. The tumors ranged from 2 to 6 cm. All contained scattered chief cells with pleomorphic nuclei, two exhibited mitoses, and three showed perineural and three vascular invasion. Follow-up was available in all 12 patients and ranged from 15 months to 28 years (average, 7.3 years). None of the tumors recurred locally, but one did metastasize to a single cervical lymph node that was apparent at the time of diagnosis. Of 13 carotid body paragangliomas examined for DNA, 4 were diploid, 3 diploid-tetraploid, 3 tetraploid, 2 aneuploid, and 1 polyploid. The only malignant tumor was polyploid. From these observations, we conclude that abnormalities in DNA content of carotid body paragangliomas are common and that tumor ploidy cannot be used to assess malignant potential. We also found no apparent relationship among nuclear pleomorphism, mitotic activity, perineural invasion, or vascular invasion and clinical behavior. Perineural and vascular invasion, however, were observed only in tumors with abnormal DNA histograms. PMID- 2317326 TI - Tumor necrosis factor and cytotoxic agents. Effect on squamous carcinoma lines. AB - The cytotoxicity of dactinomycin (actinomycin D), doxorubicin hydrochloride (Adriamycin), cisplatin, fluorouracil, and methotrexate alone and in combination with recombinant human tumor necrosis factor (rHuTNF) on human squamous cell carcinoma lines was studied by an MTT proliferation assay. The rHuTNF alone caused no inhibition after 24 to 72 hours. All lines investigated showed a dose dependent response to dactinomycin and doxorubicin. Potentiation of dactinomycin and doxorubicin cytotoxicity occurred with four of six cell lines following incubation of rHuTNF and the drug. No synergistic effect on cytotoxicity was seen with rHuTNF and any chemotherapeutic agent on two cell lines. The addition of rHuTNF did not augment the cytotoxic effect seen with cisplatin, methotrexate, or fluorouracil on any cell line. These results show that rHuTNF can enhance the cytotoxic effect of certain chemotherapeutic agents on squamous cell lines in vitro. PMID- 2317328 TI - Evaluation of mandibular tumor invasion with magnetic resonance imaging. AB - Evaluating the extent of tumor invasion of the mandible is clinically important in the management of mandibular tumors. Conventional imaging studies including panoramic radiography, bone scans, and computed tomography, as well as clinical evaluation can be unreliable in defining the extent of neoplastic marrow invasion. This study presents the initial UCLA, Los Angeles, Calif, experience with magnetic resonance imaging in evaluating mandibular invasion by benign and malignant neoplasms. Magnetic resonance imaging, using T1 and T2 images, was compared with conventional imaging methods in 11 patients with malignant lesions and nine patients with benign lesions. In all cases, magnetic resonance imaging most accurately determined the full extent of tumor invasion in the mandibular marrow spaces. Magnetic resonance imaging appears to be superior to offer clear benefits over conventional imaging methods, including computed tomography, for the evaluation of tumor invasion of the mandible. PMID- 2317329 TI - Surgical correction of the snout suffocation syndrome. AB - Two nursing home patients with difficulty breathing because of occlusion of the mouth and nares by an involuntary snout reflex-like mannerism have previously been described. In both cases advanced dementia, edentia, and a downward-angled nasal base were present. Life-threatening hypoxia occurred intermittently in one case, and after becoming severe, was corrected by the surgical procedure described. PMID- 2317330 TI - Snoring can be reduced when the nasal airflow is increased by the nasal dilator Nozovent. AB - The ability to breath through the nose can be increased above normal by dilating the narrow nasal valve area with the plastic nasal device Nozovent. For 10 nights, 10 patients used Nozovent every other night, and the sleeping partners of the patients judged the snoring sound level using a snoring score. The results showed a significant decrease in snoring, from moderate to slight, when Nozovent was used, or from a barely tolerable to a tolerable noise level. In about 1 night out of 4, when the nostrils were dilated, the sleeping partners did not note any snoring at all. An increased nasal airflow is achieved with less negative intrathoracic pressure, which presumably results in less opportunities for vibrations of the soft palate. PMID- 2317331 TI - Subglottic cysts in the premature infant. AB - Supraglottic cysts in the newborn are a well-recognized entity, but subglottic cysts have been rarely reported. Over the past 6 years we have observed subglottic cysts in nine patients with relatively long intubations from the neonatal intensive care unit of two university hospitals. Most frequently the patients were extubated and did well for weeks or months, but then they had progressive biphasic stridor. On endoscopy the patients had a subglottic stenosis that was irregular but with a smooth mucosal lining. Usually the cysts were apparent, but in two patients the mucosa was thickened and the patients were treated as a subglottic stenosis with tracheostomy. These subglottic cysts were recognized at the time of laryngotracheoplasty. In six patients the cysts were managed either by marsupialization with cup forceps, endoscopic diathermy, or carbon dioxide laser without recurrence. It is our belief that this condition is most likely due to scarring and obstruction of mucus glands of the subglottic area from prolonged intubation. This entity should be recognized and looked for in the neonate who has an acquired subglottic stenosis and should first be treated conservatively with endoscopic marsupialization. PMID- 2317332 TI - Vestibular schwannoma presenting with sudden facial paralysis. AB - Facial paralysis is an unusual manifestation of vestibular schwannoma, and generally signifies an advanced stage of tumor growth. We describe a case of eighth-nerve schwannoma that presented initially with rapid-onset complete unilateral facial paralysis. At the time of operation the nerve was found to be electrically intact despite marked compression by tumor. The facial nerve was preserved and facial motion has partially recovered postoperatively. All unexplained persistent facial paralysis should be evaluated by magnetic resonance imaging with paramagnetic contrast enhancement. PMID- 2317333 TI - Pathologic quiz case 2. Benign lymphoepithelial cyst of the parotid gland associated with HIV infection. PMID- 2317334 TI - On the cause of sinusitis in patients with cleft palate. PMID- 2317335 TI - Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: correlation with cognitive severity. AB - Diagnosis of probable Alzheimer disease (AD) is made by a combination of characteristic clinical findings, when normal laboratory studies reveal no structural or metabolic cause of the dementia. Definite diagnosis of AD, however, can only be made with brain tissue examination. PET scanning reveals parietotemporal decreases in cerebral blood flow (CBF) and glucose metabolism that differentiate AD from normal elderly and from multi-infarct dementia. Preliminary studies suggest that similar defects in CBF are detectable in single photon emission computed tomography (SPECT) in AD. Utilizing the iodinated ligand [123I] HIPDM ([123I] hydroxyiodobenzylpropanediamine), we studied 19 patients with probable AD of varying severity, with emphasis on mild cases, to assess the utility of SPECT as a diagnostic test in AD. Parietotemporal perfusion on SPECT was decreased unilaterally or bilaterally in 16 of 19 AD patients, similar to the defects reported with PET. The degree and extent of decreased CBF on SPECT correlated with AD severity. Strong correlations were obtained between decreases in computer-generated ratios of parietal to cerebellar activity and the level of cognitive function. SPECT was read as normal (on the radiographic film) by the nuclear medicine physician in all cases with Mini-Mental State (MMS) score greater than 24, and showed bilateral parietal perfusion deficits in only 1 of 4 patients with MMS between 22 and 24. Ten of 12 patients with MMS less than or equal to 21 had bilateral parietal abnormalities; the other 2 had unilateral perfusion defects. All patients with MMS less than 15 were bilaterally abnormal. SPECT is less expensive and more widely available than PET, and may have an adjunctive role in diagnosis of AD and other dementias if utilized under the proper circumstances. PMID- 2317336 TI - Immunogold labeling of Alzheimer paired helical filaments with ganglioside MAB A2B5. AB - The ganglioside monoclonal antibody A2B5 has previously been used at the light microscopic level to label Alzheimer neurofibrillary tangles (NFTs). Light microscopic analysis, however, could not reveal whether the A2B5 antibody-labeled NFTs or membrane fragments associated with NFTs. Therefore, we used pre-embedding immunohistochemical electron microscopy to examine A2B5 labeling of NFT. We found that the A2B5 antibody does indeed label a NFT antigen associated with the paired helical filament (PHF) structure, while no significant labeling of membranes or membrane fragments was observed. However, no clear periodicity of the immunogold label on the PHF was found. PMID- 2317337 TI - Impaired facial recognition memory in aging and dementia. AB - Young normals, aged normals, and patients with early and advanced probable dementia of the Alzheimer type (DAT) were administered a facial recognition memory task. A continuous recognition paradigm was used, in which subjects were instructed to identify the repeated faces in an ongoing series of faces presented on a video monitor screen. A signal detection analysis of the data revealed that the DAT patients were markedly impaired in their ability to discriminate between new and repeated faces. Multiple presentations of faces improved the recognition accuracy of the early DAT patients only, but their rate of learning was slower than that of the normal subjects. In comparison to the young normals, elderly normals exhibited a mild deficit in recognition memory. All of the elderly subject groups exhibited a more liberal response bias than the young normals, which eliminates the possibility that the impaired memory task performance of the aged subjects could be attributed to a more conservative test-taking strategy. The DAT patients exhibited impaired recognition even when the second presentation of a face immediately followed the first, which perhaps implies that task performance was also sensitive to the effect of DAT on visuoperceptual abilities or psychomotor speed. PMID- 2317338 TI - Whatever happened to those with borderline IQs? AB - Persons with IQs between one and two standard deviations below the mean constitute a group that has long been ignored by researchers in mental retardation and by programs aimed at assisting developmentally disabled people. This group used to be considered as having "borderline retardation," but these people have since become decertified. A study of 20 young adults whose IQs fell within the former borderline range was conducted to examine how they fared during the transitional year after leaving high school. Most expressed serious concerns for the future as they drifted between jobs and educational programs. More research is needed to identify the special problems of this group and devise appropriate intervention strategies. PMID- 2317339 TI - Preparing mentally retarded students for mainstreaming: priorities of regular class and special school teachers. AB - An inventory to assess instructional priorities when preparing young mentally retarded children for mainstreaming was administered to special school and regular class teachers. Regular class teachers placed a significantly higher priority on two of five academic areas and one of four behavioral problem areas than did the special school teachers. PMID- 2317340 TI - Social behavior and knowledge of social "scripts" among mentally retarded adults. AB - Mentally retarded individuals' script-based knowledge and performance of routine events was explored. Twenty mentally retarded adults and 20 nonretarded preschoolers were asked to sequence photographs of events depicted in familiar and novel contexts. Retarded individuals were better able to sequence events depicted in familiar contexts than in novel contexts, suggesting deficits in generalizing social knowledge. Preschoolers performed above chance levels in the familiar context only. Observations of retarded individuals during naturally occurring events indicated that actual social behavior was unrelated to event knowledge. PMID- 2317341 TI - Intentional and incidental memory in organically mentally retarded, familial retarded, and nonretarded individuals. AB - Groups of organically mentally retarded, familial retarded, and nonretarded subjects were compared on two tasks of intentional memory and one of incidental memory. With mental age being covaried, the familial group did better than the organic group on both tasks of intentional memory. However, the performance of both retarded groups was inferior to that of the nonretarded children. The three groups did not differ on incidental learning. The finding of differences between organically retarded and familial retarded persons supports the view that etiology needs to be considered when studying cognitive functioning in mentally retarded persons. The differences between the familial retarded and nonretarded groups appear to be in contradiction to the similar structure hypothesis of mental retardation. PMID- 2317342 TI - Ego identity in mentally retarded adolescents. AB - Ego identity and the relations between ego identity and adjustment in mentally retarded adolescents were explored. Three groups were formed: 30 mildly retarded adolescents, 30 nonretarded adolescents matched for CA, and 30 nonretarded preadolescents matched for MA. Ego identity was individually assessed using a questionnaire, and social adjustment was assessed by teachers' ratings. The identity profile of the retarded adolescents differed from that of the nonretarded peers and from that of younger preadolescents. Results suggest that identity in retarded adolescents does not reflect a simple developmental lag, but rather a unique profile. Ego identity in the retarded adolescents was also related to their social adjustment and level of functioning, even after controlling for IQ. PMID- 2317343 TI - Rigidity in mentally retarded and nonretarded children. AB - The dependence of rigidity on task difficulty was examined. The hypothesis was that mentally retarded subjects would be more rigid than would nonretarded subjects on difficult but not on easy tasks. An intelligence test and seven rigidity tests varying in difficulty were administered to 45 retarded and 45 MA matched nonretarded subjects. Factor analyses yielded one rigidity factor for the retarded group and two for the nonretarded group. In both groups the rigidity tests were interrelated and formed a Guttman simplex structure in terms of difficulty. The groups did not differ on three easy tests but did differ on four more difficult tests. The results were interpreted mainly in a motivational framework, with implications concerning mental retardation and rigidity as an interactional concept. PMID- 2317344 TI - Carbamazapine for behavioral disorders. PMID- 2317345 TI - Microwave-assisted frozen section diagnosis. A comparison between conventional cryostat technique and the combination of freezing and microwave-stimulated fixation. AB - The study evaluates the morphology of frozen tissue sections treated by microwave stimulated fixation compared with unfixed cryostat sections. Furthermore, microwave fixation has been compared with fixation at room temperature. Improved preservation of nuclear structures (chromatin pattern and nucleoli) was found with the microwave combination, while other parameters were indistinguishable from the unfixed cryostat sections. Fixation at room temperature showed no difference compared with the unfixed cryostat sections. The combined method might be useful in rapid diagnosis of mesenchymal tumors, lymphoid proliferations and tumors of the CNS. PMID- 2317346 TI - Histological evaluation of prostatic cancer. (II): Reproducibility of a histological grading system. AB - The aim of this study was to evaluate the reproducibility, expressed by kappa coefficients, of the histological grading system of prostatic cancer as proposed by Schroeder, Hop, Blom and Mostofi in 1985. This grading system has five prognostic groups based on combinations of growth pattern, mitoses and nuclear anaplasia. All histological slides from 85 cases of prostatic carcinoma were blindly evaluated on two independent occasions by each of four pathologists. The overall INTER-observer agreement and mean INTRA-observer agreement regarding "prognostic group" were 0.55 and 0.69 respectively, whereas the kappa coefficients were 0.38 and 0.57 respectively. An acceptable level of INTER observer reproducibility of prognostic group I (kappa = 0.70), of the parameter "growth pattern" (kappa = 0.60) and of "slight nuclear anaplasia" (kappa = 0.62) was found. A low overall kappa coefficient of "mitoses" and "nuclear anaplasia" was found. Based on the well reproducible parameters a simplified grading system is proposed. PMID- 2317347 TI - Histological evaluation of prostatic cancer. (III): Reproducibility of assessment of tumour volume and its possible significance for prognosis. AB - The aim of this study was to evaluate the INTER- and INTRA-observer reproducibility of prostatic cancer volume defined as the percentage of chips with carcinoma in transurethrally resected tissue. All histological slides from 80 consecutive cases of prostatic cancer were blindly evaluated on two independent occasions by each of four pathologists. The correlation was expressed by Spearman's rank correlation coefficient (R). Both the overall INTER- and mean INTRA-observer correlation of tumour volume were high with R being respectively 0.905 and 0.918. With reference to stage A1 and A2, data were transformed to an ordinal scale with 2 categories (less than = 5%, greater than 5%). The overall INTER- and mean INTRA-observer agreement of this classification were 0.926 and 0.943 respectively--the corresponding kappa coefficients being 0.68 and 0.74. It is concluded that in transurethrally resected tissue a highly reproducible index of the resected prostatic cancer volume can be given by the percentage of chips with tumour. The prognostic significance of this parameter is discussed. PMID- 2317349 TI - Quantitative estimation of diphtheria and tetanus toxoids. 4. Toxoids as international reference materials defining Lf-units for diphtheria and tetanus toxoids. AB - The Lf-unit, which is used in the control of diphtheria and tetanus toxoid production and in some countries also to follow immunization of horses for production of antitoxins, has hitherto been defined by means of antitoxin preparations. A diphtheria toxoid and a tetanus toxoid preparation, both freeze dried, were examined in an international collaborative study for their suitability to serve as reference reagents in the flocculation tests and for defining the Lf-units. It was shown that flocculation tests using the reference toxoids are very reproducible and reliable and the WHO Expert Committee on Biological Standardization established: the toxoid called DIFT as the International Reference Reagent of Diphtheria Toxoid for Flocculation Test with a defined content of 900 Lf-units of diphtheria toxoid per ampoule; and the toxoid called TEFT as the International Reference Reagent of Tetanus Toxoid for Flocculation Test with a defined content of 1000 Lf-units of diphtheria toxoid per ampoule. PMID- 2317348 TI - Postantibiotic effect of the penem FCE 22101 against selected gram-positive and gram-negative bacteria in vitro and in vivo by the use of a tissue cage model in rabbits. AB - Isolates of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae were tested for their bactericidal activity and postantibiotic effect (PAE) with the new penem FCE 22101. The tissue cage model in rabbits was used to study PAE in vivo. The bactericidal activity against all four species was shown to be in the range of 0.05-4.0 mg/l. A 99.9% killing effect at MBC concentrations was reached within 2 hours with S. pneumoniae and K. pneumoniae and within 6-8 hours with S. aureus and H. influenzae. After in vitro exposure by FCE 22101 a PAE in vitro and in vivo was obtained against S. aureus, S. pneumoniae and H. influenzae strains but no PAE could be demonstrated against K. pneumoniae. FCE 22101 showed a good bactericidal activity and PAE against the strains investigated, except for K. pneumoniae. PMID- 2317350 TI - Assessment of an end-point microassay for yellow fever vaccine. AB - A statistical analysis was performed on the results obtained in titrations of yellow fever vaccine using a cytopathic end-point microassay in the Vero cell line. The present test system appeared less sensitive than the conventional plaque assay in PS cells but the consistency in titres was satisfactory since both test-to-test and within-test variations were small. In addition, the test is easy to perform, economical and fast. PMID- 2317351 TI - An in vitro bioassay for quantitation of human interferons by measurements of antiproliferative activity on a continuous human lymphoma cell line. AB - Interferons have, in addition to their antiviral effects, been shown to possess several non-antiviral activities. In this study, an in vitro bioassay for interferon alpha (IFN-alpha) preparations based on their antiproliferative effect in cultured Daudi cells has been developed. Briefly, about 10(5) cells per ml treated with different concentrations of IFN were incubated under standard culture conditions for 3 days. Two different end points, i.e. incorporation of [3H]thymidine and final cell density, were used and responses were evaluated according to established pharmacopoeial principles for quantification of biomolecules. Both methods gave similar results. However, measurement of final cell density yielded the most precise results. The proposed assay, with an effective assay range of 1-10 IU/ml (approximately 0.2-2 x 10(-12)M, had a high sensitivity and precision as well as a good reproducibility. Compared with antiviral assays, it is less resource demanding. In conclusion, the in vitro bioassay described is well suited for potency determinations of IFN-alpha and probably also IFN-beta preparations. PMID- 2317352 TI - Quantitative estimation of diphtheria and tetanus toxoids. 3. Comparative assays in mice and in guinea-pigs of two tetanus toxoid preparations. AB - Two freeze-dried international reference tetanus toxoids of different origin and purified by different methods were compared in various potency assay systems, in vitro as well as in vivo. When the antigenic contents in the two toxoids are used as the basis for expressing the relative potency, different tests in animals gave different potencies. It is concluded that, as a result of such differences, tetanus vaccines can hardly be quantitated unambiguously in potency assays in animals. Since, however, a biological immunogenicity control seems necessary, a more simple type of test is suggested, which will require much less resources in terms of animals and manpower. PMID- 2317353 TI - A stability study of an opacity standard. AB - Three procedures were adopted to increase the stability of the Chinese National Opacity Standard so that the change in opacity was within a range of +/- 5%. PMID- 2317354 TI - The development of an enzyme-linked immunosorbent assay for measuring the potency of vaccines containing Clostridium chauvoei antigens. AB - Current standards (British Pharmacopeia (Veterinary) 1985) for vaccines containing Clostridium chauvoei require a potency test based on a challenge assay in guinea-pigs. Animal welfare and cost considerations favour the development of alternatives. Most veterinary clostridial vaccines are multi component, requiring assays in rabbits to test the potency of components other than C. chauvoei. We describe the application of an ELISA to measure the response to C. chauvoei vaccines in rabbits. The antigen is a sonicated extract of C. chauvoei strain CH4, intended to include a mixture of cellular and soluble antigens. The rabbit response to more than 70 vaccines containing C. chauvoei has been assessed against a reference serum which has been assigned an arbitrary potency of 100 units ml-1. The antibody titres of rabbit sera have been compared with the results of guinea-pig challenge potency tests on the same vaccines. The pass level in the guinea-pig potency test is equivalent to a rabbit ELISA titre of 50 units ml-1. PMID- 2317356 TI - Report--from the European Collection of Animal Cell Cultures. PMID- 2317355 TI - [A simple method for assaying the activity of adsorbed tetanus toxoids]. AB - The authors have developed a simplified activity test for Tetanus Toxoids Adsorbed, based on the comparison of antitoxin levels in mice 4 weeks after injection of a reference toxoid and of the vaccine to be tested. Titration of tetanus antitoxin is achieved by passive agglutination of turkey RBC sensitized by means of glutaraldehyde. After preliminary experiments establishing feasibility of this method, the authors have obtained reproducible and quantitative results. They observed an increase of the immune response by a booster and an immunostimulation when pertussis component is present. They have found close correlation in immunized mice between the titre of circulating antibodies and the survival/death response after challenge by tetanus toxin as done in the official control. This simplified method using a reduced number of animals, yields, nevertheless, quantified results with confidence limits. Thus it is suitable for laying down a norm and can in many cases take the place of the official potency test which is tedious, expensive and often criticized. PMID- 2317357 TI - The influence of sound stimulus parameters on the acoustic reflex waveform. AB - The transient increase in admittance seen at the beginning of the acoustic reflex response in man was investigated with a view to reaching a better understanding of its possible mechanisms. The sound stimulus intensity, its duration and its off-time were varied to investigate their effects on the morphology of the admittance waveform. The results found suggest that the transient increase may not be due to a temporary partial decoupling of the ossicular chain during the initial stages of stapedial contraction, but rather that it may be caused by a slight improvement in the coupling between the middle ear components. PMID- 2317358 TI - An evaluation of the relationship among electronystagmographic, audiologic, and self-report descriptors of dizziness. AB - Although descriptions of dizziness constitute a major category of complaints among patients seen in many clinical practices, the actual significance of the patient's report of symptoms has been disputed. Furthermore, the relationship of report to outcomes of clinical tests of the audio-vestibular system has not been well described. The present study examined the relationship of a self-report measure to results of electronystagmographic and audiometric evaluations in a consecutive sampling of patients at a Veterans Administration Medical Center. The findings reflected poor predictability of peripheral vestibular involvement when using the self-reporting questionnaire by patients, even when combined with audiometric observations. The utility of the self-report approach is discussed. PMID- 2317359 TI - Immunocytochemical localization of mitochondrial and cytosolic aspartate aminotransferase isozymes in the vestibular end-organs of rats. AB - The localization of mitochondrial (m-) and cytosolic (c-) aspartate aminotransferase (AAT) was examined in the vestibular ganglion neurons and sensory cells in the vestibular end-organs of rats by an indirect immunohistochemical method using antibodies specific for m- and c-AAT. Neurons in the vestibular ganglion were stained by both m- and c-AAT antibodies, but the vestibular sensory cells exhibited only m-AAT-like immunoreactivity and were not labeled by c-AAT. These findings suggested that aspartate is a neurotransmitter in the hair cells of the vestibular end-organs. PMID- 2317360 TI - Adherence of Haemophilus influenzae to nasal, nasopharyngeal and buccal epithelial cells from patients with otitis media. AB - Since mucosal colonization may be an important determinant in the pathogenesis of otitis media with effusion (OME), we studied the adherence of Haemophilus influenzae (HI) to human nasal, nasopharyngeal, and buccal mucosal cells obtained from patients with OME. Non-typeable HI adhered in significantly greater numbers than type b HI. HI bacteria adhered to both nasal and nasopharyngeal mucosal cells in significantly greater numbers than to buccal ones. Non-typeable HI adhered to the epithelial cells from children with chronic sinusitis in more significant numbers than did those from children without chronic sinusitis. These results indicate that non-typeable HI adhere more readily to epithelial cells and that the nasal and nasopharyngeal mucosa may be an important route for HI infection in OME. PMID- 2317361 TI - Changes in tympanograms after middle ear inflation. AB - To determine the effects of politzerization or middle ear (ME) inflation by a catheter, we studied the ME pressures in 35 ears with retracted tympanic membranes (29 patients). Serial tympanometries were performed prior to the ME inflation and immediately, 10, 20, 30 and 60 min after the procedure. The present study showed that the more negative the ME pressure was before the inflation, the greater the pressure change was after the treatment. The elevated ME pressure induced by the procedure declined rapidly within the first 20 min after the inflation. This was probably caused mainly by spontaneous elimination of ME gas through the eustachian tube and gas absorption from the ME mucosa. During the post-inflation course, some ears demonstrated more negative pressures in the ME cavity than those before the inflation. The present investigation demonstrated that the use of inflation to treat secretory otitis media had short-term benefits which could be improved by minimizing gas absorption. PMID- 2317362 TI - Nasal myiasis due to Oestrus ovis larvae. AB - Herein we report our experiences in managing nasal infestation due to fly larvae in an urban population. The nasosinus location is infrequently seen in cases with human infection. The life cycle of the fly (Oestrus ovis) is discussed in view of the clinical features of our case. PMID- 2317363 TI - Cholesteatoma in the oval window niche. AB - The histopathological changes in the oval window niche into which a cholesteatoma is spreading are described in 14 temporal bones. Extension of the matrix into the niche was found commonly. In some cases the matrix passed from the facial canal to the promontory but failed to reach the niche. The perimatrix of the cholesteatoma was composed of inflamed and vascularized granulation tissue or fibrocystic tissue. A matrix covering the walls of the niche and the footplate of the stapes or the oval window was rarely found. It was surrounded by a thin layer of non-inflamed fibrous or fibrocystic tissue which covered the niche. Bone destruction of the superstructures of the stapes was observed in 12 of the 14 cases examined. The footplate of the stapes was partially or totally destroyed in 4 cases. Bone destruction of the tympanic portion of the facial canal adjacent to the oval window niche was present in all cases. Our present studies further suggest that surgical removal of a cholesteatoma from the niche may be difficult, even when done very carefully. PMID- 2317364 TI - Ultrastructural pathology of the vestibule in patients with acoustic neurinomas: secondarily operated cases after posterior fossa operation. AB - The vestibular sensory epithelia from two patients with acoustic neurinomas were examined ultrastructurally. Both patients had first undergone posterior fossa operations 8 months and 3 years before residual tumors in the acoustic canals were removed by a secondary translabyrinthine operation. Labyrinthine sensory tissues were also removed for microscopic studies. In case 1, the utricular macula and the lateral and anterior cristae were observed, with all sensory epithelia showing fairly normal findings. Myelinated nerve fibers below the sensory epithelia also appeared normal. In case 2, only the utricular macula could be observed. The sensory epithelium showed severe degeneration, disappearing sensory cells and increasing cytoplasmic filaments of both the sensory cell and the supporting cell. Myelinated nerve fibers below the sensory epithelia were only rarely found. PMID- 2317365 TI - Susceptibility of the endocochlear potential to pH and osmolarity changes in the perilymph of the cochlea in the guinea pig. AB - The effects of artificial perilymph at various pH levels and osmolarities on the endocochlear potential (EP) were investigated in a guinea pig model. In 47 ears, the mean EP was 74.5 +/- 0.5 mV in the second turn of the cochlea before perilymphatic perfusion. The artificial perilymph with a pH ranging from 5 to 9 and tonicity less than 1.25 (osmolarity, 345 mosmol/l) did not alter the EP when testings were recorded for at least 1 h. However, after the start of a perfusion with a pH less than 4, the EP declined gradually but recovered to the pre perfusion level rapidly when the perfusion was stopped. The artificial perilymph with a pH over 10 decreased the EP considerably but showed no recovery, even after cessation of the perfusion. Tonicity more than 1.35 (osmolarity, 372.6 mosmol/l) also decreased the EP, with this decrease paralleling further increases in the tonicity used. From these data, we have concluded that a perilymph perfusate with a pH from 5 to 9 and an osmolarity less than 350 mosmol/l can be used in animal testing without any noxious effects on the EP. PMID- 2317366 TI - A rapid and versatile method for the detection and isolation of mammalian cell lines secreting recombinant proteins. AB - The secreted-protein agarose diffusion immunoassay (SADI) described here is an efficient and time-saving method for identifying cell lines secreting recombinant protein products. In addition to significantly reducing the labor involved in identifying clones of interest, it also increases the possibility of detecting rare transformants by allowing the screening of a large number of clones simultaneously. The recovery of viable cell lines following the technique is nearly 100%. We demonstrate that the assay can be used to differentiate between clones producing two different protein products and that it is possible to use the technique to identify and isolate the high-producing recombinant clones in a population. Given an available antiserum, it should be possible to adapt this assay for any secreted protein of interest. PMID- 2317367 TI - Sequencing products of the polymerase chain reaction directly, without purification. AB - An improvement over current protocols for sequencing products of the polymerase chain reaction is described. This method allows sequencing products of the reaction without performing costly, time-consuming purification steps which often result in unacceptable loss of product. Conservation of small amounts of polymerase chain reaction products which can be obtained from limited DNA sources, such as tissue biopsies, is achieved. Clarity of autoradiograms obtained utilizing this adaptation is comparable to that obtained with the original method. In addition to streamlining the amplification-sequencing procedure, this procedure can potentially be subjected to total automation. PMID- 2317368 TI - A simple and easy-to-assemble device for polymerase chain reaction. AB - In this paper we describe an efficient polymerase chain reaction device which is easy to assemble and requires minimal investment in dedicated equipment. The polymerase chain reaction device consists of three waterbaths, three dual-head peristaltic pumps, an electronic timer and a fabricated water jacket capable of holding microcentrifuge tubes. This device has been successfully used to amplify human factor X genomic DNA in our laboratory. PMID- 2317369 TI - Increased efficiency of oligonucleotide mutagenesis by removal of endogenous primers from preparations of single-stranded M13 DNA. PMID- 2317370 TI - Use of a fluorescent chloramphenicol derivative as a substrate for CAT assays. PMID- 2317371 TI - Avoiding woody plant DNA sample loss when loading submarine agarose gels for electrophoresis. PMID- 2317372 TI - Mini-prep in ten minutes. PMID- 2317373 TI - A simple and rapid method for the preparation of total plant DNA. PMID- 2317374 TI - Removal of yeast contamination from lymphoblast cultures. PMID- 2317375 TI - Optimization of asymmetric polymerase chain reaction for rapid fluorescent DNA sequencing. AB - A high-throughput method for the preparation of single-stranded template DNA, which is suitable for sequence analysis using fluorescent labeling chemistry, is described here. In this procedure, the asymmetric polymerase chain reaction is employed to amplify recombinant plasmid or bacteriophage DNA directly from colonies or plaques. The use of amplification primers located at least 200 base pairs 5' to the site of sequencing primer annealing removes the need for extensive purification of the asymmetric polymerase chain reaction product. Instead, the single-stranded product DNA is purified by a simple isopropanol precipitation step and then directly sequenced using fluorescent dye-labeled oligonucleotides. This method significantly reduces the time and labor required for template preparation and improves fluorescent DNA sequencing strategies by providing a much more uniform yield of single-stranded DNA. PMID- 2317376 TI - Chromosome assignment by polymerase chain reaction techniques: assignment of the oncogene FGF-5 to human chromosome 4. AB - We describe a new chromosomal assignment method based on the polymerase chain reaction mediated amplification of target sequences in DNAs from somatic cell hybrids. The new method is faster, much more sensitive and less labor intensive than the standard method of chromosome assignment by Southern hybridization analysis of somatic cell hybrid DNAs. The feasibility of the new approach was demonstrated by verifying the assignment of the previously mapped acidic fibroblast growth factor gene to human chromosome 5. The method was employed to assign the related oncogene, FGF-5, to human chromosome 4. PMID- 2317377 TI - Paralog chromatography. AB - As a mixed mode ligand, a small peptide can mimic an antibody's paratope (antigen recognition site). This report describes the construction of a representative set of paratope analogs, or "paralogs," which can be conjugated to a chromatographic sorbent to combine desirable characteristics of traditional high-performance liquid chromatography columns with the specificity of a moderate affinity antibody. The broad utility of this novel set of protein separatory reagents is illustrated on the complex mixture of proteins in a yeast lysate. PMID- 2317378 TI - A two-dimensional acrylamide gel electrophoresis/computer software approach to decoding the human genome. AB - The human genome sequencing initiative is sure to be an expensive and time consuming project. To maximize the quality of the initial thrust, it is necessary to concentrate on sequencing those genes that are actively involved in crucial biological processes, both normal and otherwise. To identify the protein products of these genes, we propose the use of two-dimensional acrylamide gel electrophoresis and powerful computer software. The two-dimensional gels can then be scaled to yield sufficient amounts of the protein for direct amino acid sequence analysis. The amino acid sequence then provides the direct link back to the gene. PMID- 2317379 TI - Heteropolymeric potassium channels expressed in Xenopus oocytes from cloned subunits. AB - Voltage-dependent potassium currents were measured in Xenopus oocytes previously injected with RNAs generated in vitro from each of three cloned cDNAs (RBK1, RBK2, and RGK5). The currents differed in their sensitivities to blockade by tetraethylammonium (TEA; respective KDs 0.3, greater than 100, and 10 mM) and in their inactivation during a depolarizing pulse. Injections of RNA combinations (RBK1/RBK2 and RBK1/RGK5) caused currents that had TEA sensitivities different from those expected from the sum, in any proportion, of the two native channels. It is concluded that novel potassium channels are formed by the oocytes injected with two RNAs, presumably by heteropolymerization of subunits; such heteropolymerization would contribute functional diversity to voltage-dependent potassium channels in addition to that provided by a large gene family. PMID- 2317380 TI - Visinin: a novel calcium binding protein expressed in retinal cone cells. AB - Visinin is a retinal cone cell-specific protein (molecular weight 24,000, pI 5.1). To investigate its function, visinin cDNA was isolated from a chick retinal lambda gt11 cDNA library, using anti-visinin serum. The beta-galactosidase visinin fusion protein was used for purifying epitope-selected antibody. The purified visinin antibody reacted only with a 24 kd protein in retinal cone cells. Visinin mRNA was expressed only in the retinal photoreceptor layer. The nucleotide sequence of the cDNA revealed that visinin has three E-F hand structures and is a Ca2+ binding protein. Visinin protein expressed in E. coli exhibited Ca2+ binding activity. These results suggest that visinin is a photoreceptor-specific Ca2+ binding protein and may be involved in phototransduction in the cone cells. PMID- 2317381 TI - Sudden cortical blindness following transient enhancement of steroids administered in congenital adrenal hyperplasia (case report). AB - A case of cortical blindness developed in an infant who suffered from congenital adrenal hyperplasia and was hospitalized for enteritis is reported. The severe but transient hypertension recorded raises the possibility that the increased doses of steroid administered may have contributed to the pathogenesis of visual impairment. PMID- 2317382 TI - Surgical management of neonates and children with ambiguous genitalia. AB - Gender assignment is a neonatal surgical emergency. Early evaluation and treatment of intersexuality must be done as a team approach with a genetist, a paediatric endocrinologist and a paediatric surgeon/urologist taking part in it. Change of gender after 2 years of confusion of gender identity often results in social disaster. Over a period of 20 years the authors managed a total of 27 patients with ambiguous genitalia. They favour early reconstruction of most anomalies at about 3 years of age, which seems to be optimal in terms of surgical feasibility and avoidance of the obvious emotional problems caused by delayed intervention. A detailed description of policy and techniques is given for surgical intervention in the patient to be raised as a female or as a male. They changed the gender in three patients, twice in neonates and once before two years of age. PMID- 2317384 TI - Interaction of monocyte Fc receptors with monovalent and polyvalent ligands. PMID- 2317383 TI - Normocaloric diet and exercise: a good choice for treating obese adolescents. AB - The results of a slimming treatment in which the main features were: energy intake according to expected body weight for height (normocaloric), exercise, education and psychological support, are evaluated after one year of experience. Twenty-four obese adolescents (15 boys and 9 girls), out of thirty who started treatment, completed this stage successfully. Pubertal changes occurred and growth continued normally, mainly of lean body mass, as shown by the increase of lean body weight and muscle area of the mid-upper arm. A substantial loss of fat, expressed in a reduction of fat weight, relative fatness and fat areas of the mid upper arm was obtained. Body weight for height shifted to lower percentile channels. The results are promising in indicating the successful treatment of obese subjects in a period of rapid growth without affecting their normal development, profiting also from the usually-observed decrease in fatness at this age. In view of the success in motivating most of the subjects to maintain the continuity of diet and physical activity, this method is considered a good choice for treating obese adolescents without severe energy restriction, thus assuring lasting effects instead of the short-term ones commonly reported in the literature. PMID- 2317385 TI - Modulation of Fc gamma receptors in the membrane of human monocytes: effect on monocyte functions. PMID- 2317386 TI - G6P-DH Santa Clara and G6P-DH Villa Clara: two new Cuban variants. AB - Two new glucose 6-phosphate dehydrogenase G6P-DH variants designated G6P-DH Santa Clara and G6P-DH Villa Clara were identified in a Cuban family. These variants belong to class III. Their electrophoretic and kinetic properties allow the conclusion that G6P-DH Santa Clara and G6P-DH Villa Clara are probably two new variants. PMID- 2317387 TI - Hypercalciuria and postglomerular hematuria in children. The effects of thiazide on calcium excretion, urine saturation with respect to calcium-hydrogenphosphate and hematuria. AB - Calcium-hydrogenphosphate was considered as one of the main factors governing renal calculus formation. The degree of saturation (expressed as activity product = AP) with respect to this phase was therefore calculated in urines of 36 hypercalciuric children (20 absorptive, 16 renal subtype) with isolated hematuria and 30 healthy controls. The effect of thiazide treatment on the urine saturation and on the evolution of hematuria was also investigated. The results were compared to the urinary calcium excretion (expressed as Ca/cr ratio). Urines of both hypercalciuric groups were saturated on basal conditions (AP above 3.5 x 10 6 mol2/l2; -lgAP below 6.4), the values differed significantly from those of the controls (-lgAP = 6.78 +/- 0.4 in the control-; 6.1 +/- 0.25 in absorptive-, 6.03 +/- 0.34 in renal hypercalciuria; p less than 0.001). Thiazide normalized the activity product in all groups. During thiazide therapy significant decrease in the occurrence of hematuria was noted (p less than 0.001 in both hypercalciuric groups). These data furnish further evidence on the relation of hypercalciuria and postglomerular hematuria. Simultaneous determinations of the state of saturation may provide further information on the "stone forming potential" of the urines investigated. PMID- 2317388 TI - Chromosome examinations on six-hour cultures of unstimulated peripheral blood from some patients with childhood leukemia. AB - Six-hour cultures of unstimulated peripheral blood cells from patients with various types of childhood leukemias were examined for chromosome karyotypes. It was found that this method was suitable for the detection of characteristic chromosomal abnormalities in two cases of acute nonlymphoblastic leukemias (ANLL; FAB types M3 and M6) and in a case of chronic myelogenous leukemia (CML), but not in acute lymphoblastic leukemias (ALL). The results suggest the usefulness of this simple method (possibly in combination with the thymidine boost technique of Yunis) in the cytogenetic diagnosis of some types of leukemias. PMID- 2317389 TI - Future structure of the BDA. PMID- 2317390 TI - Reasonable remuneration? PMID- 2317391 TI - 'Wisdom tooth waiting lists'. PMID- 2317392 TI - Waste not... PMID- 2317393 TI - 'Changing perceptions of the requirements of cavity preparations'. PMID- 2317395 TI - Failed eruption of the permanent canine following open reduction of a mandibular fracture in a child. AB - A 10-year-old patient with failed eruption of the right mandibular canine associated with a retained metal plate previously placed to reduce a mandibular body fracture is presented. The incidence and site of mandibular fractures related to the developing permanent dentition and the relevance of this to popular methods of fixation employed in the reduction of fractures is discussed. PMID- 2317394 TI - The Brain laryngeal mask. An alternative to difficult intubation. AB - We report the case of a young man undergoing fixation of bilateral mandibular fractures, where the anaesthetist was unable to intubate. A Brain laryngeal mask was employed, thus enabling surgery to proceed. This relatively new device enabled the airway to be safeguarded whilst preserving reasonable surgical access for the attachment of Erich arch bars and a four hole osteosynthetic bone plate. The surgical and anaesthetic procedures are summarised. The laryngeal mask is described and its performance and limitations are discussed. We believe this to be the first report of mandibular fracture fixation performed with a Brain laryngeal mask in situ. PMID- 2317396 TI - Treatment of Class II malocclusions with removable appliances. Part 2. Class II division 1 treatment. AB - It is possible, with careful case selection, to achieve good orthodontic results using removable appliances, provided that they are well designed and properly adjusted. The best way to measure progress is to divide the treatment plan into stages, with each stage having recognisable objectives that must be achieved before moving on to the next stage. PMID- 2317397 TI - The MGDS: a candidate's view--Part 2. PMID- 2317398 TI - Ki aikido: a solution to stress. AB - It is common knowledge that the life of the general dental practitioner is extremely stressful. Different dentists resort to various ways of unwinding- perhaps a game of golf, a sailing trip, or mending the odd clock as occupational therapy. These are all ways of getting away from the stress of day-to-day work- but perhaps the time has come to look for a more fundamental solution. How many dentists have considered taking up a martial art to alleviate the problem of stress? Here, we outline the background of ki aikido and its practical applications in daily life. PMID- 2317399 TI - Redkino to Rutland--a glimmer of Glasnost. AB - Margaret Herd met Vladimir Nikitin on a BDJ study tour in the Soviet Union in March 1988. As a result of their meeting Margaret moved heaven and earth to help Vladimir come for a taste of the West. He spent a month in Britain last Christmas, encountering with awe and disbelief the many everyday things that we take for granted. Here Margaret describes Vladimir's brief visit. PMID- 2317400 TI - Operation Himalaya! AB - Primary health care is more than a luxury for many of the world's poorest countries. The charity, Action Health 2000, is attempting to develop dental services in, among other places, the northern provinces of India. Linda Hillman answered their advertisement and found herself among the people of the 'God King'. PMID- 2317401 TI - Undergraduate teaching of hypnotherapy and its uses in the United States. AB - American dental students are able to study hypnotherapy. In Britain no such facility exists. In order to ascertain the feasibility of introducing hypnotherapy into the undergraduate curriculum in Britain I attended an elective in clinical hypnosis at the University of California, Los Angeles. PMID- 2317402 TI - Ambulatory pulmonary arterial pressure in primary pulmonary hypertension: variability, relation to systemic arterial pressure, and plasma catecholamines. AB - The variability of pulmonary arterial pressure, the relation of pulmonary pressure to systemic pressure, pulmonary pressure responses to stimuli (exercise, hypoxia, smoking, free ambulation), and plasma catecholamine responses were assessed in five patients with primary pulmonary hypertension. Ambulatory monitoring techniques provided data for the computerised analysis of continuous, beat-to-beat, direct recordings of both pulmonary and systemic arterial pressures for 8 to 10 hours. The absolute variability of pulmonary arterial pressure and the magnitude of absolute changes in this variable in response to stimuli were increased in primary pulmonary hypertension. The variability of systemic pressure was similar to that in healthy volunteers. Basal and stimulated plasma catecholamine values were normal, suggesting preservation of normal sympathetic nervous system activity in primary pulmonary hypertension. PMID- 2317403 TI - Enhanced morphological diagnosis in infective endocarditis by transoesophageal echocardiography. AB - Thirty three consecutive patients with clinically suspected endocarditis were studied by both precordial cross sectional echocardiography and transoesophageal echocardiography. The diagnostic value of both techniques was assessed. The data were compared with findings at operation in 25 patients. In 21 patients with native valve endocarditis precordial echocardiography showed evidence of vegetations in six patients and suggested their presence in nine. Transoesophageal echocardiography identified vegetations in 18 patients. Complications were seen in four patients at precordial echocardiography and in nine patients at transoesophageal echocardiography. Precordial echocardiography did not show vegetations in any of the 12 patients with prosthetic valve endocarditis whereas transoesophageal echocardiography showed vegetations in four. Complications were seen in four patients at precordial echocardiography and in 10 at transoesophageal echocardiography. Echocardiographic findings were confirmed at operation in all 25 operated patients. In two patients both echocardiographic techniques had missed the perforation of the cusps of the aortic valve that was seen at operation, but this had no effect on patient management. Transoesophageal echocardiography is the best diagnostic approach when infective endocarditis is suspected in patients with either native or prosthetic valves. PMID- 2317404 TI - Familial restrictive cardiomyopathy with atrioventricular block and skeletal myopathy. AB - Five generations of an Italian family with an autosomal dominant restrictive cardiomyopathy are described. Members of four generations were examined. Symptoms usually developed in the third or fourth decade but the disease did occur in childhood. Initially the condition was characterised by normal ventricular size and systolic function with increased diastolic filling pressures in both ventricles and consequent bi-atrial enlargement. Cardiac catheterisation showed a left ventricular filling pattern of "dip and plateau". The electrocardiogram typically showed non-specific changes in the ST segment and T wave and changes indicating considerable atrial enlargement, which were confirmed by echocardiography. Light microscopy of two endocardial biopsy specimens showed no specific features but excluded the endomyocardial fibrosis of eosinophilic heart disease, amyloid, and specific heart muscle diseases. At necropsy in one case examined under light microscopy extensive patchy fibrosis was found throughout the endocardium, myocardium, and subepicardium, but there were no features typical of eosinophilic heart disease. Histopathological and biochemical examination of skeletal muscle identified no abnormality. The disease often had an insidious course over five to ten years after presentation. Bundle branch blocks, leading to complete atrioventricular block, however, often occurred and may be the first manifestation. Some individuals who survived into the fifth decade developed a progressive, non-wasting skeletal myopathy. PMID- 2317405 TI - Cardiac involvement in congenital myotonic dystrophy. AB - Seven young patients (mean age 19 years 8 months) with congenital myotonic dystrophy and with defined symptoms at birth were investigated by electrocardiography and echocardiography. None had cardiovascular symptoms. Electrocardiograms or echocardiograms or both were abnormal in all patients. Atrioventricular and intraventricular conduction defects were the most common electrocardiographic abnormalities and were seen in five patients. The echocardiographic examinations showed impaired left ventricular systolic function in one patient. Other echocardiographic findings were a small left ventricle and atrium, minor valve defects, and mitral valve prolapse. This study shows that the heart is often affected in young patients with congenital myotonic dystrophy. The specialised conduction system is often affected and so too is the myocardium, causing impaired systolic function. PMID- 2317407 TI - Blood filled cyst of the papillary muscle of the mitral valve producing severe left ventricular outflow tract obstruction. AB - A 46 year old man was found to have left ventricular outflow obstruction caused by a blood-filled cyst attached to the anterior papillary muscle of the mitral valve. It was successfully excised. PMID- 2317406 TI - Abnormalities of the spleen in relation to congenital malformations of the heart: a survey of necropsy findings in children. AB - A series of 1042 reports of necropsies on children dying at Children's Hospital of Pittsburgh was reviewed. In each case, note was taken of the status of the spleen, the lobation of the lungs, the arrangement of the bronchi, the morphology of the atrial appendages, and the presence of any congenital malformations of the heart and great vessels and of any malformations of the abdominal organs. There was isomerism of the left atrial appendages in eight (0.77%), 13 (1.25%) showed isomerism of the right appendages, and seven (0.67%) had multiple spleens without having isomerism of the atrial appendages. Unexpectedly, a normal spleen was found in one patient with isomerism of the right appendages and also in a patient with isomerism of the left appendages. In one patient with isomeric left atrial appendages there was no spleen. The review showed that the morphology of the atrial appendages, and hence the arrangement of the atria, is not accurately predicted by the type of spleen. The arrangement of the atrial appendages is the most reliable guide to the recognised combinations of congenital cardiac malformations previously described as "splenic syndromes". Because there is no certain way of predicting all the malformations in patients with complex congenital heart disease, it is advisable to record separately for each patient the details of lobation of the lungs, the bronchial and atrial arrangement, anomalies of the heart and great vessels, the type of spleen, and any abnormal arrangement of the abdominal organs. PMID- 2317408 TI - Gonococcal arthritis complicated by acute pericarditis and pericardial effusion. AB - A woman of 23 presented with a painful, swollen left knee. A thick yellow fluid aspirated from the joint cavity grew Neisseria gonorrhoeae. Central pleuritic chest pain and ST segment elevation developed 48 hours after presentation. These signs and symptoms of pericarditis had settled two months after the acute illness. PMID- 2317409 TI - Low pressure cardiac tamponade: diagnosis facilitated by Doppler echocardiography. AB - A case of low pressure cardiac tamponade is reported in which hypovolaemia altered the clinical findings of tamponade and complicated the diagnosis. Venous pressure was not raised and there was no pulsus paradoxus. In this patient, a man of 67, characteristic variations in diastolic inflow signals and the isovolumic relaxation period throughout the respiratory cycle were shown by Doppler echocardiography and led to the diagnosis of cardiac tamponade in the absence of characteristic signs and symptoms. PMID- 2317410 TI - Should coronary angiography be performed in district hospitals? PMID- 2317411 TI - Major complications of coronary arteriography: the place of cardiac surgery. AB - The records of the catheter laboratory at St George's Hospital between 1983-1988 were reviewed to determine how often emergency coronary bypass surgery was performed because of a complication arising during elective coronary arteriography. A total of 11,216 cardiac procedures were performed; 5781 were confined to left ventricular angiography and coronary arteriography in patients with suspected coronary artery disease. Fourteen patients, whose investigation had been considered routine, suffered profound circulatory collapse during the procedure. Emergency cardiac surgery was undertaken in 13, with long term survival in 10. This experience suggests that, even in patients considered to be at low risk, there were major complications requiring emergency coronary surgery in at least 2.4 per 1000 coronary arteriograms performed. Survival after emergency cardiac surgery in these patients was 77%. These findings and the access to cardiac surgery should be considered when the development of facilities for cardiac catheterisation is planned. PMID- 2317412 TI - High density lipoprotein cholesterol and triglycerides as markers of angiographically assessed coronary artery disease. AB - Serum triglycerides, high density lipoprotein (HDL) cholesterol, and total cholesterol were measured in 698 patients examined by angiography. The ratio of HDL cholesterol to total cholesterol was significantly lower in patients with single, double, and triple vessel disease than in patients without disease. The serum concentration of triglyceride was significantly higher in patients with single, double, and triple vessel disease than in those without coronary artery disease. Similar proportion of patients with coronary artery disease and without had serum cholesterol concentrations of greater than or equal to 6.5 mmol/l, but total cholesterol was significantly higher in patients with single, double, and triple vessel disease than in those without. HDL cholesterol (less than 1.0 mmol/l), triglycerides (greater than 2.0 mmol/l), and the ratio of HDL cholesterol to total cholesterol (less than 0.20) were significantly better than total cholesterol as indicators of coronary risk. PMID- 2317414 TI - Lipid peroxidation during myocardial ischaemia induced by pacing. AB - Oxygen derived free radical generation can be shown in experimental models of myocardial ischaemia and reperfusion and may cause cellular damage by peroxidizing polyunsaturated membrane phospholipids. An attempt was made to quantify human intracardiac lipid peroxidation during transient myocardial ischaemia by measuring the aortic and coronary sinus concentrations of malondialdehyde (a marker of lipid peroxidation) before, during, and after incremental pacing. Twenty six patients were paced until they had severe chest pain or 2 mm ST segment depression or they reached a paced rate of 180 beats/min. They were divided into two groups according to whether or not lactate was produced during pacing. Twelve patients (group 1), all with coronary artery disease, produced myocardial lactate during pacing. None of the other 14 patients (group 2), half of whom had coronary disease, produced lactate during pacing. Concentrations of malondialdehyde in the aorta and coronary sinus were significantly higher in group 1 than in group 2. Five minutes after the end of pacing coronary sinus malondialdehyde concentrations in group 1 had increased significantly from baseline values. There were no changes with time in the coronary sinus concentration of malondialdehyde in group 2 or in the aorta in either group. The negative malondialdehyde extraction ratio in group 1 suggests that intracardiac lipid peroxidation occurs during transient human myocardial ischaemia. PMID- 2317413 TI - Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment. AB - Activated neutrophils releasing proteolytic enzymes and oxygen free radicals have been implicated in extending myocardial injury after myocardial infarction. Neutrophil elastase was used as a marker of neutrophil activation and the non peroxide diene conjugate of linoleic acid was used as an indicator of free radical activity in 32 patients after acute myocardial infarction; 17 were treated by intravenous thrombolysis. Patients with acute myocardial infarction had higher plasma concentrations of neutrophil elastase and the non-peroxide diene conjugated isomer of linoleic acid than normal volunteers or patients with stable ischaemic heart disease. Patients treated by thrombolysis had an early peak of neutrophil elastase at eight hours while those who had not been treated by thrombolysis showed a later peak 40 hours after infarction. The plasma concentration of non-peroxide conjugated diene of linoleic acid was highest 16 hours after the infarction irrespective of treatment by thrombolysis. Quantitative imaging with single photon emission tomography showed decreased uptake of indium-111 labelled neutrophils in the infarcted myocardium (as judged from technetium-99m pyrophosphate) in those who had received thrombolysis, suggesting a decreased inflammatory response. The results indicate increased neutrophil activation and free radical production after myocardial infarction; they also suggest that thrombolysis does not amplify the inflammatory response and may indeed suppress it. PMID- 2317415 TI - Non-invasive determination of cardiac output by Doppler echocardiography and electrical bioimpedance. AB - Cardiac output measured by thermodilution in 25 patients within 24 hours of acute myocardial infarction was compared with cardiac output measured by Doppler echocardiography (24 patients) and electrical bioimpedance (25 patients). The mean (range) cardiac outputs measured by Doppler (4.03 (2.2-6.0) 1/min) and electrical bioimpedance (3.79 (1.1-6.2) 1/min) were similar to the mean thermodilution value (3.95 (2.1-6.2) 1/min). Both non-invasive techniques agreed closely with thermodilution in most patients. None the less, three results with each method disagreed with thermodilution by more than 1 1/min. Both non-invasive techniques were reproducible and accurate in most patients with acute myocardial infarction. Doppler echocardiography was time consuming and technically demanding. Electrical bioimpedance was simple to use and had the additional advantage of allowing continuous monitoring of the cardiac output. PMID- 2317416 TI - Peroperative nitrous oxide delays bowel function after colonic surgery. AB - Forty patients scheduled for elective colonic surgery were allocated at random to receive either nitrous oxide or air during surgery. Preoperative management, surgery, parenteral therapy and postoperative analgesics were similar in both groups. Anaesthetic management included isoflurane, vecuronium by infusion and fentanyl 3 micrograms kg-1 h-1. The air group required a mean inspired isoflurane concentration of 0.8% (SD 0.3), whereas the nitrous oxide group required 0.4% (SD 0.2). No differences were found in duration of operation, blood loss, need for postoperative analgesia or postoperative nausea. Patients in the air group had less gas in the small bowel (P less than 0.005) and in the large bowel (P less than 0.001), and operating conditions were better than in the nitrous oxide group (P less than 0.01). After operation, the air group had significantly earlier bowel function than the nitrous oxide group, with earlier passing of flatus (3.4 (1.2) vs 4.7 (1.4) days) (P less than 0.05) and faeces (4.7 (1.5) vs 6.3 (2.2) days) (P less than 0.05) and required a shorter postoperative hospital stay (10.0 (1.3) vs 11.7 (2.5) days) (P less than 0.05). PMID- 2317418 TI - Effects of enflurane on visual evoked potentials in humans. AB - Effects of enflurane on visual evoked potentials (VEP) were studied in eight healthy female patients. Control VEP were recorded from the occipital electrode (OZ-CZ), and prominent negative (N70) and positive (P100) peaks were observed following flash light stimulation. After induction of anaesthesia with thiopentone, VEP were recorded at expired concentrations of 1.2, 1.8, 2.4 and 2.7% of enflurane in 100% oxygen. The amplitude of the P100 was decreased and the latency of the N70 was increased significantly from the control with all concentrations of enflurane. No significant difference was found between different concentrations of enflurane. The latency of the P100 was increased significantly only at concentrations above MAC and at 2.7% when it was significantly longer than those at 1.2 and 1.8%. We conclude that VEP are altered significantly with enflurane in clinically used concentrations. PMID- 2317417 TI - Isoflurane sedation for patients undergoing mechanical ventilation: metabolism to inorganic fluoride and renal effects. AB - The metabolism and renal effects of isoflurane sedation were studied for 24 h in patients undergoing mechanical ventilation. Forty-six patients admitted to our intensive therapy unit were allocated randomly to receive either 0.1-0.6% isoflurane or midazolam 0.01-0.2 mg kg-1 h-1 for sedation. In 26 patients sedated with isoflurane, plasma inorganic fluoride increased from a mean concentration of 4.03 mumol litre-1 to 13.57 mumol litre-1 12 h after stopping sedation. Plasma inorganic fluoride concentrations in 20 patients sedated with midazolam were unchanged from baseline values (mean 5.32 mumol litre-1). Serum electrolyte, urea and creatinine concentrations, and urine output rates during and after sedation in patients who received isoflurane were similar to those who received midazolam. We conclude that, following isoflurane sedation for up to 24 h, metabolism to inorganic fluoride is insufficient to cause clinical renal dysfunction. PMID- 2317419 TI - Oxygen saturation during inhalation induction with halothane and isoflurane in children: effect of premedication with rectal thiopentone. AB - Anaesthesia was induced by inhalation in 100 children using nitrous oxide in oxygen supplemented by either halothane or isoflurane, with or without rectal thiopentone premedication. Respiratory problems occurred more frequently in the unpremedicated isoflurane group, resulting in significant reductions in oxygen saturation. Premedication reduced the frequency of these complications, and oxygen saturation was usually maintained. PMID- 2317420 TI - Spinal analgesia with plain 0.5% bupivacaine administered at spinal interspace L2 3 or L4-5. AB - Forty patients (age range 60-79 yr) undergoing transurethral surgery were allocated randomly to receive 0.5% plain bupivacaine 4 ml at the L2-3 (n = 20) or L4-5 (n = 20) space. The solution was injected over 30 s with the patient in the sitting position. The patient was kept sitting for 2 min, then placed supine and, 5 min later, placed in the lithotomy position. No significant differences were found in onset time, extent and duration of analgesia or duration of motor block. PMID- 2317422 TI - Comparison of complications associated with single-holed and multi-holed extradural catheters. AB - Adverse events associated with single-holed and multi-holed extradural catheters were compared in obstetric practice. Two hundred and forty-five patients were given an extradural block using a single-holed catheter and 229 received a block via a multi-holed catheter. There was no difference in the incidence of major side effects. Flow of fluid under gravity in the catheter was restricted significantly more often in the single-holed catheters. Blood was found significantly more often in the multi-holed catheters. PMID- 2317421 TI - Depth and duration of skin analgesia to needle insertion after topical application of EMLA cream. AB - We have determined the depth and duration of analgesia to needle insertion after topical application of EMLA cream (Eutectic Mixture of Local Analgesics). EMLA was applied for 30, 60, 90 and 120 min and the sensory and pain threshold depths were determined before analgesia (1.0 and 1.9 mm, respectively) and up to 4 h after the cream was removed from the skin. The maximal depth of analgesia (approx. 5 mm) was observed 30 min after a 90-min application and during the 60 min period after a 120-min application of EMLA cream, for both sensory and pain thresholds. For application times shorter than 120 min, the depth of analgesia increased during the period after removal of the cream. This suggests new guidelines for the use of this topical analgesic. PMID- 2317423 TI - Effect of dantrolene on ventilation and respiratory muscle activity in anaesthetized dogs. AB - The effect of dantrolene on ventilation and ventilatory muscle activity was evaluated in spontaneously breathing anaesthetized dogs. When administered as a bolus of 1.5 mg kg-1 i.v., dantrolene caused hypercapnia. Under isocapnic conditions, with end-tidal PCO2 maintained at 8.1 (SEM 0.3) kPa by adjusting inspired carbon dioxide, dantrolene decreased tidal volume from 475 (66) to 254 (46) ml and breathing rate from 21 (4) to 15 (3) b.p.m. (P less than 0.01 for both). Occlusion pressure was reduced, but the rate of rise of the diaphragm and intercostal EMG were unchanged and peak activity increased only as a result of prolongation of inspiration. Respiratory variables returned gradually to baseline values 1 h after dantrolene administration. Phrenic nerve stimulation revealed a marked reduction in the ability of the diaphragm to generate pressure, particularly at low frequencies of stimulation. Only partial recovery was observed after 1 h. It is concluded that dantrolene causes hypoventilation in the anaesthetized dog when given in large doses i.v. PMID- 2317424 TI - Effect of glucose concentration on the intrathecal spread of 0.5% bupivacaine. AB - We have studied the effects of intrathecal injection of 0.5% bupivacaine in solutions containing different concentrations of glucose (0.33%, 0.83% and 8%) in three groups of 10 patients. The mean maximum extent of sensory block was significantly higher with 8% glucose (T3.6) than with 0.83% glucose (T7.2) or 0.33% glucose (T9.5). Administration of solutions containing 0.33% glucose produced a greater variability in upper level of sensory block (11 dermatomes) than the two other concentrations (six dermatomes each). The rate of onset of sensory block to T12 was fastest with solutions containing 8% glucose. Complete motor block of the legs was produced in every patient. PMID- 2317426 TI - Enhanced thromboxane synthesis with extradural anaesthesia. AB - Reperfusion of a limb following tourniquet ischaemia increases plasma concentrations of thromboxane (TxB2). The study examined TxB2 production during the ischaemia and reperfusion of femoral-popliteal bypass surgery and the effect of anaesthetic technique. Patients (n = 19) were randomly allocated to receive either general (GA) or extradural (EA) anaesthesia. TxB2 concentrations were similar both before and after anaesthesia in the two groups. Clamping the femoral artery in patients given GA resulted in a small but insignificant increase in TxB2 concentration. However, in the EA group clamping resulted in a 10-fold increase in TxB2 concentration (P less than 0.05). To demonstrate that anaesthesia itself was not the stimulus to TxB2 synthesis, patients undergoing inguinal herniorrhaphy (n = 13) received either GA or EA. There were no subsequent changes in TxB2 concentrations in each group. The results indicate that EA but not GA maintains collateral flow during femoral arterial clamping and provides the oxygen needed for generation of TxB2 during ischaemia. PMID- 2317425 TI - Effect of humidification on inhalation induction with isoflurane. AB - Forty-two patients undergoing inhalation induction with isoflurane in nitrous oxide and oxygen, were allocated randomly to receive either humidified or non humidified gas. Humidification resulted in a significantly lower incidence of problems during induction (P less than 0.05). PMID- 2317427 TI - Effect of nicardipine on the cardiovascular response to tracheal intubation. AB - We studied the cardiovascular responses to laryngoscopy and intubation in 30 patients who received nicardipine 15 micrograms kg-1 or 30 micrograms kg-1, or saline placebo 60 s before the start of laryngoscopy. Anaesthesia was induced with thiamylal 5 mg kg-1 i.v. and tracheal intubation was facilitated with vecuronium 0.2 mg kg-1. Patients receiving saline showed a significant increase in mean arterial pressure (MAP) and rate-pressure product (RPP) associated with tracheal intubation. The increases in MAP and RPP following tracheal intubation were reduced in both groups of patients who received nicardipine. PMID- 2317428 TI - Profound respiratory depression after extradural fentanyl. AB - A case is described of profound respiratory depression occurring 100 min after the extradural administration of fentanyl 100 micrograms to a patient undergoing Caesarean section. PMID- 2317429 TI - Fibrodysplasia ossificans progressiva. AB - A 14-yr-old boy with fibrodysplasia ossificans progressiva (FOP) presented for surgery for bilateral division of his ossified masseter muscles. Patients with FOP may present problems to the anaesthetist, including difficulties with tracheal intubation, restrictive pulmonary disease and abnormalities of cardiac conduction. With our patient sedated the trachea was intubated using a fibrescope and anaesthesia was induced and maintained with nitrous oxide and enflurane in oxygen. Ventilation was controlled throughout surgery and recovery was uneventful. PMID- 2317430 TI - Pharmacokinetics of buccal morphine. PMID- 2317431 TI - Doxapram and the neuromuscular junction. PMID- 2317433 TI - Another AIDS controversy. PMID- 2317432 TI - Blind nasal intubation is no longer necessary. PMID- 2317434 TI - Non-steroidal anti-inflammatory drugs and gastrointestinal bleeding in the elderly. AB - Cases of gastrointestinal bleeding associated with non-steroidal anti inflammatory drugs (NSAIDs) were analysed. Forty per cent of the 92 cases admitted with gastrointestinal bleeding were found to be on NSAIDs. Sixty per cent of the cases on NSAIDs had a preceding history of dyspepsia or ulcer disease and its complications. Forty per cent presented with spontaneous bleeding. We discuss some of the aspects of the management of these cases in clinical practice. PMID- 2317435 TI - ACE inhibitors and diuretics causing hypokalaemia. AB - Angiotensin-converting enzyme (ACE) inhibitors and diuretics are known to cause hyperkalaemia. We undertook a prospective analysis over a period of six months of patients admitted under our care. Of 217 patients, 39 (18 per cent) were admitted with congestive cardiac failure/left ventricular failure. Of these 39 patients, 21 (54 per cent) were prescribed ACE inhibitors. Seven of these 21 patients subsequently developed hypokalaemia. This was irrespective of the type or dose of the diuretic but seemed to be related to the dose of the ACE inhibitor. In three cases the hypokalaemia was corrected by the addition of a potassium-sparing diuretic; in two cases a potassium supplement was added; and in the other three an increase in the dose of the ACE inhibitor for the resistant heart failure corrected the potassium deficit. This study shows that one should be alert to both hyperkalaemia and hypokalaemia when using a combination of ACE inhibitors and diuretics. PMID- 2317437 TI - Chronic active hepatitis, pyoderma gangrenosum and febrile panniculitis. PMID- 2317436 TI - Acute intussusception: referral in relation to presentation and aetiology. AB - A study of 42 consecutive children with acute intussusception was undertaken. The emphasis was on the time taken for surgical referral in relation to the presenting symptom. Operative findings and outcome revealed late referral (greater than 72 h) in cases presenting with diarrhoea and bleeding per rectum. A higher incidence of gangrenous gut and irreducibility of intussusception was found in the ileoileal variety of intussusception. Some interesting facts about the aetiology have also been noted. Rupture of intussuscipiens was also encountered. PMID- 2317438 TI - Psychiatric presentation of a venous angioma of the frontal lobe. PMID- 2317439 TI - Ingestion of dishwasher detergent by children. PMID- 2317441 TI - Intra-vaginal torsion of the testis occurring in a neonate. PMID- 2317440 TI - Surgical complications of fulminating meningococcaemia. PMID- 2317442 TI - Comparison of the effectiveness of slow-release propranolol (Inderal LA) 80, 160 and 320 mg orally daily in the treatment of angina pectoris. AB - Doses of 80, 160 and 320 mg of Inderal LA (slow-release propranolol) were compared in 12 patients with stable angina pectoris. There was an unpredictable and variable individual response to treatment and hence no differences were detected between the effects of the three doses on mean treadmill exercise duration, time to angina, frequency of angina or glyceryl/trinitrate consumption. There was a marked deterioration in two patients whilst on 320 mg Inderal LA. In these patients, the time to angina fell by 2 minutes 50 seconds and 4 minutes 20 seconds on 320 mg daily and 160 mg daily respectively. Given the inter-patient variability in response to Inderal LA, the dose for each patient should be individually titrated according to response. Two patients reported here suggest that some subjects may benefit from lower doses, although further work is required to clarify this point. Possible explanations for this finding are discussed. PMID- 2317443 TI - Cultured epithelia from junctional epidermolysis bullosa letalis keratinocytes express the main phenotypic characteristics of the disease. AB - Keratinocytes from a 1-week-old male infant with junctional epidermolysis bullosa letalis (JEBL) were grown in vitro and then grafted as multi-layered epithelia onto nude mice, to investigate whether the defect in the dermo-epidermal cohesiveness in the disease is of epidermal and not mesodermal origin. In culture, there was a birefringent ring of cells at the edges of the keratinocyte colonies and in places some cells looked as though they had been ejected from the periphery of the colony. At confluence, the multi-layered epithelia were easily detached from the culture flasks using only mechanical agitation. On microscopy the fully-differentiated epithelium on days 21, 30 and 40 after grafting sometimes showed blistering at the dermal-epidermal junction. No labelling was noted using a GB3 monoclonal antibody, that reacts with normal human keratinocytes in culture and with the dermo-epidermal basement membrane zone in normal skin. This indicates that the defect of JEBL may be reproduced in culture and also after grafting the cultured epithelial onto a wound without an epidermis. This suggests a possible role for the junctional structure recognized by GB3 in dermo-epidermal cohesiveness. PMID- 2317444 TI - A dose-response study of UVB-induced suppression of contact photosensitivity in the mouse. AB - A marked contact photosensitivity (CPS) response to 3,3',4',5 tetrachlorosalicylanilide (TCSA) plus UVA was induced in mice. Cyclophosphamide (Cy), given prior to sensitization, caused a further increase in ear swelling. When UVB radiation was given at a site distant from that used for sensitization it caused a dose-related suppression of CPS. Cy did not eliminate the UVB-induced suppression. PMID- 2317445 TI - Pharmacodynamic measurements of methyl nicotinate percutaneous absorption: the effect of aging on microcirculation. AB - The penetration of drugs through aged skin is important both in terms of transdermal delivery to elicit systemic pharmacological effects, and for topical treatment. Cutaneous microcirculation efficiency, an integral parameter in the overall process of percutaneous absorption, was studied in young (20-34 years) and old (64-86 years) individuals. Cutaneous erythema as induced by topical administration of methyl nicotinate to the ventral forearm, was monitored non invasively using laser-Doppler flowmetry. Dose-response behaviour was characterized by five parameters: (i) the time of onset of action; (ii) the time to reach maximum response; (iii) the magnitude of the maximum response; (iv) the area under the response-time curve; and (v) the time to decay to 75% of the maximum response. Additionally, the sensitivity and efficiency of the cutaneous microcirculation in both age groups was evaluated using a pharmacokinetic pharmacodynamic model. Statistical analysis of all data showed no significant differences between the age groups for the same concentrations. The results indicate that microvessel reactivity to the applied stimulus is comparable in the ventral forearm of both young and old populations. PMID- 2317447 TI - The eosinophil granulocyte in psoriasis. AB - The presence of eosinophils and eosinophil cationic protein (ECP) in the involved and non-involved skin in patients with psoriasis was studied using a polyclonal antibody specific for ECP and a monoclonal antibody (EG2) specific for activated eosinophils and secreted ECP. ECP immunoreactive eosinophils were found in all the specimens from involved psoriatic skin. In new lesions in patients with rapidly progressive disease, intense ECP immunoreactivity was detected both intra and extracellularly, particularly in the upper third of the epidermis and usually in association with granulocytes. In stable or slowly progressive lesions, less ECP was observed. The EG2-immunoreactivity was positive in the same areas. ECP was also determined in suction-blister fluid from lesional and non involved skin in psoriasis patients and in healthy subjects. The ECP concentration was greatly elevated in the fluid from lesions in patients with more acute and progressive disease. PMID- 2317446 TI - The effect of cyclosporin on human epidermal keratinocytes in vitro. AB - Cyclosporin A has been shown to be effective in the treatment of severe, recalcitrant psoriasis, but it is uncertain whether the mode of action is primarily by immune suppression or by other mechanisms. Cyclosporin-dependent growth-inhibition has recently been demonstrated in vitro using several non-human and transformed epithelial cell lines. In this study the effect of cyclosporin on human epidermal keratinocytes and skin fibroblasts was investigated. Secondary cultures of human epidermal keratinocytes were grown on collagen-coated dishes in the presence of increasing concentrations of cyclosporin. Inhibition of growth was observed at 6-8 microM. An almost identical dose-response curve was obtained for the cytotoxic drug, cis-platin. Short-term exposure (I h) to cyclosporin did not have any effect on epidermal cell growth, suggesting that direct membrane related effects were not involved. Analysis of cellular proteins by SDS-PAGE indicated no effect of continuous cyclosporin exposure on in vitro differentiation. The observation that human epidermal keratinocyte growth is inhibited by cyclosporin suggests that a topical form of therapy for psoriasis may be an effective alternative to oral treatment. PMID- 2317448 TI - Investigation of skin by ultraviolet remittance spectroscopy. AB - Remittance spectroscopy in the ultraviolet spectral region was used to investigate human skin in vivo. Untreated healthy skin showed a minimum remittance at 280 nm wavelength, corresponding to the keratin absorption band. At shorter wavelengths the remittance mostly originated from light scattering in the stratum corneum and at longer wavelengths subcorneal structures had increasing influence. The spectral remittance reflected variations in pigmentation most sensitively in the UVA region. Hydration of the skin yielded a hypsochromic shift of the keratin absorption band due to changes in polarity and proton concentration in the environment of the chromophores. Remittance spectroscopy allows detection of topically applied drugs, whose penetration into the skin can be evaluated from the time-dependence of the remittance. PMID- 2317449 TI - Homozygous variegate porphyria: a case report. AB - Homozygous variegate porphyria is described in a 14-year-old girl with a unique clinical presentation of photosensitivity from the second year of life, mental retardation, clinodactyly, and normal growth rate. The erythrocyte protoporphyrin concentration was raised with the protoporphyrin being predominantly zinc chelated, which appears to be characteristic for all homozygous hepatic porphyrias. Protoporphyrinogen oxidase activity in lymphoblasts was decreased in both patient and parents despite the latter having normal porphyrin excretion. PMID- 2317450 TI - British Society for Investigative Dermatology. Annual meeting. Birmingham, September 1989. Abstracts. PMID- 2317451 TI - Pneumocystis carinii pneumonia following methotrexate. PMID- 2317452 TI - Long-term survival and late relapses in acute leukaemia in adults. AB - 34 out of 403 apparently unselected adult patients with acute leukaemia referred to a single department from 1970 through 1989 survived more than 3 years. The cumulative rate of relapse after 3 years was 39% in patients with acute myeloblastic leukaemia (AML) and 74% in patients with acute lymphoblastic leukaemia (ALL). The latest relapse was observed 75 months after diagnosis in AML and 98 months after diagnosis in ALL. 65% of the long-term survivors were able to undertake normal physical activity, 26% had decreased activity, and 9% were unable to work. 5-year survival for all patients, whether treated or not, during two successive decades was 16% versus 18% and 5% versus 6%, respectively, for ALL and AML. The departmental results were identical with population-based national results. Only in patients 15-49 years of age with AML was there evidence that more intensive treatment had led to better survival. PMID- 2317453 TI - Induction of eosinophilic colonies by interleukin-5 on acute myeloblastic leukaemic cells. AB - The effect of interleukin-5 (IL-5) on blast colony formation of acute myeloblastic leukaemia (AML) cells was studied. IL-5 showed a weak but significant colony stimulatory effect in one out of six cases studied. IL-5 induced eosinophilic colony growth in this case, and chromosomal and histochemical analyses strongly suggested that these eosinophilic colonies were derived from leukaemic blast progenitor cells. To our knowledge, this is the first report that IL-5 induces eosinophilic colonies on fresh AML cells. A possible induction of differentiation of AML blast cells by IL-5 is suggested. PMID- 2317454 TI - P47 phosphoprotein of blood platelets (pleckstrin) is a major target for phorbol ester-induced protein phosphorylation in intact platelets, granulocytes, lymphocytes, monocytes and cultured leukaemic cells: absence of P47 in non haematopoietic cells. AB - Aggregating agents including phorbol esters which activate protein kinase C induce the rapid phosphorylation of a Mr = 47,000 cytosolic protein in blood platelets (P47 or pleckstrin). This protein is well resolved by analytical 16-BAC ---SDS two-dimensional PAGE and was purified from platelets by preparative 16-BAC ---SDS PAGE. Polyclonal antibodies were raised to the protein in mice and rabbits. These antisera detected a single protein with the migration of P47 on Western blots of platelet extracts, and the rabbit antisera immunoprecipitated 32P-labelled P47 from platelet cytosol. The presence of P47 in other haematopoietic cells was determined by prelabelling them with 32P and observing increased 32P incorporation into the location of P47 on autoradiographs of 16-BAC ---SDS analytical PAGE of cells exposed to phorbol ester. The identity of the phosphoprotein found in this location was further established by probing Western blots of SDS PAGE gels of cultured cell lines with the P47 antisera. P47 was detected in peripheral blood lymphocytes, monocytes and granulocytes (including the granulocytes of two unrelated patients with X-linked chronic granulomatous disease). P47 was also found in HL-60 promyelocytes (especially after differentiation with retinoic acid), U937 histiocytes, HEL leukaemia cells, and Raji 'B' lymphoblasts. It was not detected in normal erythrocytes, K562 leukaemic cells, MOLT-3 'T' lymphoblasts, or in wide range of non-haematopoietic cell lines. We conclude that P47 is a major target for the action of phorbol ester induced phosphorylation in platelets, normal leucocytes and some haematopoietic cell lines. These cells have as their common feature the ability when stimulated to develop adhesive functions on their plasma membranes. PMID- 2317455 TI - Genetic thrombocytopenia with autosomal dominant transmission: a review of 54 cases. AB - On the basis of a retrospective study of 3600 platelet kinetic studies, we have isolated 54 cases with chronic thrombocytopenia, a normal autologous and homologous platelet lifespan, and increased mean platelet volume without Dohle bodies, the absence of any functional platelet abnormalities, and a normal megakaryocyte count. These cases were either discovered during the first few years of life (i.e. constitutional) and/or were proven to be familial (autosomal dominant transmission). Previous treatments (corticosteroids, immunoglobulins, androgens, immunosuppressor agents, splenectomy) were not effective in any of these cases or in their relatives. A new syndrome can therefore be proposed which can easily be suspected on the basis of platelet kinetic studies performed in cases of early onset, increased platelet volume, failure of corticosteroids or evidence of a familial blood disorder. It can be proved when the autologous platelet life span is demonstrated to be normal in spite of a chronic thrombocytopenia and a normal megakaryocytic count. The recognition of this syndrome will avoid neonatal complications (cephal-haematomas), surgical complications, and the use of expensive and possibly harmful ineffective treatments, both in the propositus and in other abnormal family members. The syndrome is certainly frequent (54 cases are presented here), but the diagnosis is often missed or delayed due to the low risk of haemorrhage. However, it is associated with a certain risk of leukaemia (four cases in three families). PMID- 2317456 TI - Alloimmunization to the PlA1 platelet antigen: results of a prospective study. AB - The natural history of alloimmunization to the PlA1 platelet antigen is uncertain. We followed 50 PlA1-negative pregnant women during pregnancy and for 6 months post-partum in order to determine this natural history. The cohort of PlA1 negative women was obtained by PlA1 typing 5000 women. Three PlA1-negative women formed anti-PlA1 antibodies during this prospective study, two in pregnancy and one in the immediate post-partum period. All three PlA1 antibody producers were HLA-DR3 positive, a histocompatibility phenotype that is strongly associated with alloimmunization to the PlA1 antigen. One of the three infants delivered to these mothers was thrombocytopenic (platelet count 9 x 10(9)/l). The remaining two infants had normal platelet counts at birth (160 and 174 x 10(9)/l). The HLA-A1, B8, -DR3 and -DRw52 phenotype frequencies in the group of PlA1-negative women who did not form PlA1 antibodies (n = 47) was similar to that found in their husbands, and that expected in a normal Caucasian population. From our data we estimate that alloimmunization to the PlA1 antigen occurs in approximately one out of every 1000 pregnancies in a Caucasian population. It is important to recognize that not all pregnancies in which a mother has formed PlA1 alloantibodies will result in the delivery of a thrombocytopenic infant. These findings are relevant to programs designed to either prevent alloimmunization to the PlA1 antigen (through passive administration of anti-PlA1 immunoglobulin to at-risk PlA1-negative mothers), or to identify women at risk of delivery of thrombocytopenic infants (by antenatal screening to detect women alloimmunized to the PlA1 antigen). PMID- 2317457 TI - Platelet activation by CD9 monoclonal antibodies is mediated by the Fc gamma II receptor. AB - The function of the human cell surface CD9 antigen is not known, yet monoclonal antibodies (mAbs) of the IgG1 subclass in the CD9 cluster induce activation of platelets. Previously it had been shown that this activation pathway is comparable both in kinetics and extent to physiological agonists such as thrombin. Here it is demonstrated that activation with CD9 mAbs depends on interaction of the Fc part of the CD9 antibody molecule with Fc receptors on the platelet surface, since: (i) mAb directed against the Fc receptor totally blocked the platelet response to CD9 mAb; and (ii) F(ab')2 fragments of the CD9 mAb SYB-1 which bound to platelets, as demonstrated by flow cytometry, failed to activate them. Furthermore, platelet activation by CD9 mAb closely paralleled the activation caused by cross-linking Fc receptors when comparing: (i) kinetics and extent of aggregation; (ii) thromboxane synthesis; (iii) calcium flux; and (iv) the cytoplasmic alkalinization response. Thus it is concluded that CD9 antigen itself does not necessarily participate in stimulus-response coupling leading to platelet activation by CD9 mAbs, and that this activation can be entirely accounted for by the Fc receptor pathway mechanism. The results suggest a possible novel mechanism for platelet consumption in cases of immune thrombocytopenia. PMID- 2317459 TI - Bone marrow trephine biopsies as a source of nucleic acids for molecular diagnosis of haematological neoplasms. PMID- 2317458 TI - Re-evaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenic purpura: a report on 53 cases. AB - We treated 53 adults (mean age 54 years, range 17-89; 37 females and 16 males) with chronic idiopathic thrombocytopenic purpura (ITP) by azathioprine. All patients had received at least one form of therapy (including splenectomy in 40 patients) and had less than 50 x 10(9)/1 platelets. The duration of ITP before azathioprine was started ranged from 6 to 350 months (median 19). All patients initially received 150 mg/d of azathioprine. This was associated with a short initial course of prednisone (0.3-0.5 mg/kg d) in 10 of them, who were refractory to prednisone alone. 34 (64%) patients responded, including 24 (45%) complete remissions (CR), three (6%) partial remissions (PR) and seven (13%) minor responses (MR). Median time to achieve response was 4 months. 17 of the CR persisted after 7-182 months, 10 of them after discontinuation of azathioprine. Seven patients relapsed after 4-26 months, five of them after azathioprine was stopped or its dose was reduced. PR were short and the median duration of MR was 8 months. Overall, 21 patients (40%) had responses lasting 1 year or more and 17 (32%) lasting 2 years or more. Median duration of treatment was 18 months (range 3-84). Five patients died of bleeding while on treatment. No prognostic factors for response to azathioprine were found. Mild leucopenia was seen in seven patients and a moderate (x3) increase in transaminases in two patients. No opportunistic infections were seen and no malignancy has occurred since the onset of azathioprine. We conclude that azathioprine gives a relatively high incidence of durable responses and very limited side effects in chronic ITP, when splenectomy has failed or is contraindicated. This efficacy, in our experience, is superior to that obtained with other therapeutic approaches. As responses may be delayed, a course of azathioprine of 4 months is required before one can infer a failure to respond. In responding patients, however, the optimum duration of treatment remains to be established. PMID- 2317460 TI - Hodgkin's disease and memory loss: another case of the Ophelia syndrome. PMID- 2317461 TI - High levels of soluble interleukin-2 receptor in the serum of 30 patients with idiopathic hypereosinophilic syndrome. PMID- 2317462 TI - Ascorbate for the treatment of refractory idiopathic thrombocytopenic purpura. PMID- 2317463 TI - Complete remission duration and long-term survivors (LTS) in chronic myelogenous leukaemia (CML): a theoretical approach to a clinical decision. PMID- 2317464 TI - Phenytoin sodium and magnesium sulphate in the management of eclampsia. AB - Twenty-two patients with eclampsia were randomly allocated to receive either intravenous phenytoin sodium or intravenous magnesium sulphate. The groups were comparable. No side-effects occurred and therapeutic levels were obtained in both groups. While none of the 11 patients managed with magnesium sulphate had further convulsions, four of the 11 treated with phenytoin sodium did and were subsequently effectively treated with magnesium sulphate. These results suggest that phenytoin sodium is not as effective an anticonvulsant in eclampsia as is magnesium sulphate. PMID- 2317465 TI - Malignant melanoma of the vulva: a clinicopathological study of 50 women. AB - A clinicopathological review of 50 primary malignant melanomas of the vulva in the West Midlands region of England is presented. The overall 5-year-survival rate was 35%, when adjusted for age. Significant predictors of survival were clinical stage, patient age, tumour ulceration, cell type and mitotic rate. Tumour thickness was of prognostic importance but as a prognostic variable it did not operate independently of stage and as most lesions were deeply invasive at presentation vulval tumours must be separated for prognostic purposes into bands at greater overall thicknesses than those used for skin melanomas generally. There was no significant relation between survival and type of surgery performed as a primary therapeutic procedure. PMID- 2317466 TI - Social support and pregnancy outcome. AB - A total of 509 women with a history of a low-birthweight (LBW, less than 2500 g) baby were recruited from the antenatal booking clinics of four hospitals and randomized to receive either a social support intervention in pregnancy in addition to standard antenatal care (the intervention group) or standard antenatal care only (the control group). At recruitment to the study, mean gestational age was 6 weeks, mean maternal age was 28.0 years, 86% of the women had one previous LBW baby, 11% had two and 2% had had three or more. The study population was socially disadvantaged: 77% of the women were working class, 18% had unemployed partners and 41% were smoking at booking. Social support was given by four research midwives in the form of 24-h contact telephone numbers and a programme of home visits, during which the midwives provided a listening service for the women to discuss any topic of concern to them, gave practical information and advice when asked, carried out referrals to other health professionals and welfare agencies as appropriate, and collected social and medical information. Pregnancy outcomes were assessed using obstetric case-note data (obtained for 507 women) and a postal questionnaire sent to all mothers 6 weeks after delivery (94% replied). Babies of intervention group mothers had a mean birthweight 38 g higher than that of control group babies; there were fewer very low-birthweight babies in the intervention group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317467 TI - Change in ovarian arterial compliance during the human menstrual cycle assessed by Doppler ultrasound. AB - Ovarian arterial velocimetry, using real-time two-dimensional and pulsed Doppler ultrasound, was performed on 36 occasions in nine healthy women with regular menstrual cycles. The change in ovarian arterial compliance was based on the calculation of pulsatility index (PI). In the active ovary carrying a dominant follicle or corpus luteum, the PI in the early follicular phase (mean 6.97, SD 2.01) was significantly higher than that in the late follicular phase (mean 2.36, SD 0.31) (P less than 0.001), and the PI in the early luteal phase (mean 0.68, SD 0.09) was significantly lower than that in the late follicular phase (P less than 0.001). The PI in the late luteal phase (mean 0.93, SD 0.16) was significantly higher than that in the early luteal phase (P less than 0.01). In the inactive ovary, no cyclical changes were seen in the values of PI. There was a significant difference between the values of PI in the active ovary and the inactive ovary in the late follicular, the early and the late luteal phases [2.36 (SD 0.31)] vs [6.29 (SD 1.02)], [0.68 (SD 0.09)] vs [6.18 (SD 1.33)], [0.93 (SD 0.16) vs [6.57 (SD 1.72)] (P less than 0.001), respectively. Use of non-invasive Doppler ultrasound to study physiology of ovarian haemodynamics during the menstrual cycle is of great clinical relevance and paves the way for further investigations on sterility. PMID- 2317468 TI - Endemic placenta accreta in a population of remote villagers in Papua New Guinea. AB - Using a combination of prospective registration of definite cases (n = 47) and retrospective identification of probable cases (n = 22) over a 6.5-year period, we have estimated that the rate of placenta accreta in the Milne Bay Province of Papua New Guinea is at least 1.6 per 1000 births, and probably in excess of 2.3 per 1000. This is substantially higher than other reported estimates of the frequency of this condition, which causes significant maternal morbidity. The study population of 130,000 consisted mainly of subsistence cultivators who live in remote hamlets, and included about 27,600 women between the ages of 15 and 49 years. A number of factors seem likely to be important in the aetiology of the condition in Milne Bay Province, including infection associated with previous childbirth and abortion. Over three-quarters of the cases would have been prevented if all women of para greater than or equal to 4 or with a history of retained placenta had used effective contraception. Better obstetric care, including early treatment of postpartum sepsis and incomplete abortion, may also help to reduce the frequency of placenta accreta in this population. PMID- 2317469 TI - Listeriosis revisited: the role of the obstetrician. AB - The clinical course and outcome is described of three pregnancies complicated by listeriosis encountered during a 6-month period. All three ended in preterm labour characterized by the passage of meconium by the fetus. Two babies died in the early neonatal period and the third survived with neurological handicap. Although the diagnosis of listeriosis was made only after delivery, all the mothers had a pyrexial illness before delivery. A high index of suspicion is needed for the early detection and prompt treatment of this life-threatening perinatal infection. Effective advice concerning prevention of listeriosis by avoidance of high-risk foods must be given to women during pregnancy. PMID- 2317470 TI - Endometrial hyperplasia in an oophorectomized woman receiving tamoxifen therapy. Case report. PMID- 2317471 TI - Ligneous conjunctivitis involving the cervix. Case report. PMID- 2317472 TI - Resistance of leaf and stem fractions of tropical forage to chewing and passage in cattle. AB - The voluntary intake (VI) of separated leaf and stem fractions of a grass and legume (Panicum maximum and Lablab purpureus respectively) was determined using Hereford steers fistulated at the rumen and oesophagus. VI of leaf fractions was higher than that of the stem fraction (8.23 v. 3.67 kg/d, P less than 0.001) while that for the legume diets was higher than for the grass diets (6.65 v. 5.22 kg/d, P less than 0.05). The total number of eating chews per day was higher on the leaf than stem fraction (1.6 x 10(4) v. 9.8 x 10(3), P less than 0.05). The mean number of rumination chews (2.4 x 10(4)) was similar (P greater than 0.05) for all four diets. The mean resistance of large particles (LP, i.e. retained on a 1.18 mm sieve during wet sieving) to breakdown (chews per g LP breakdown) during eating was lower for leaf than stem fractions (8.4 v. 23.7) and lower for the grass than legume diets (10.5 v. 21.6). The mean resistance to breakdown of LP by rumination (chews per g LP breakdown) was lower in leaf than in stem fractions (8.2 v. 13.2, P less than 0.01) and higher in grass than in legume (12.5 v. 9.0, P less than 0.05). The resistance of LP to breakdown during rumination was higher than during eating for the grass diets, but was lower for the legume. Fractional passage rates (FPR) of small particles (i.e. passing through a 1.18 mm sieve during wet sieving) from the reticulo-rumen were negatively related to dimensions of particles, with greater ease of outflow for legume than for grass particles of the same length or diameter. When corrected for content of cellulase-indigestible fibre, FPR of small particles of leaf was greater than for small stem particles. It was concluded that VI of tropical forages was associated with the resistance of LP to breakdown by chewing during both eating and rumination and that the patterns of escape of small particles from the reticulo-rumen were only partially explicable in terms of particle dimensions, and that other properties of the particles may be of importance. PMID- 2317473 TI - Excretion of purine derivatives by ruminants: endogenous excretion, differences between cattle and sheep. AB - The endogenous urinary excretion of the purine derivatives allantoin, uric acid and xanthine plus hypoxanthine were measured in twenty-nine lambs, ten cattle (six steers, one cow and three preruminant calves) and four pigs. The sheep and mature cattle were nourished by intragastric infusion and the calves were given a milk-substitute. The pigs were fed on a purine-free diet. The excretion of total purine derivatives was substantially greater by the cattle, being 514 (SE 20.6) mumol/kg live weight (W)0.75 per d compared with 168 (SE 5.0) mumol/kg W0.75 per d by the sheep and 166 (SE 2.6) mumol/kg W0.75 per d by the pigs. Plasma from normally fed sheep, cows and pigs was incubated with either xanthine or uric acid. Sheep and pig plasma had no xanthine oxidase (EC 1.2.3.2) activity whereas plasma from cattle did. Uricase (EC 1.7.3.3) was not present in plasma of cattle and pigs and appeared to be present in trace amounts only in sheep plasma. It is suggested that the species differences in endogenous purine derivative excretion were probably due to the different profiles of xanthine oxidase activity in tissues and particularly in the blood. This is because a high xanthine oxidase activity would reduce the chance to recycle purines, by increasing the probability of degradation to compounds which could not be salvaged. PMID- 2317474 TI - Excretion of purine derivatives by ruminants: effect of exogenous nucleic acid supply on purine derivative excretion by sheep. AB - The present study examined the relationship between the supply of exogenous nucleic acid (NA) purines and their recovery as the derivatives hypoxanthine, xanthine, uric acid and allantoin in urine. Six lambs, totally nourished by intragastric infusions of volatile fatty acids (VFA) and casein (i.e. no rumen fermentation), were given by abomasal infusion a microbial NA concentrate at six levels (from zero to 24.5 mmol purines/d). The true digestibility between the abomasum and terminal ileum of the NA purines was measured in a separate experiment using three lambs. The relative proportion of urinary allantoin increased, and that of other derivatives decreased, as the amount of NA infused was increased. The relationship between total excretion of purine derivatives (Y; mmol/d) and exogenous purines absorbed (X; mmol/d) was Y = 0.84X + 0.150W0.75 e 0.25X, where W is body-weight (kg). This implies that the endogenous contribution to the total excretion of derivative decreased as the supply of exogenous purines increased, with an associated progressive replacement of de novo synthesis by exogenous purines. The model also implies that 0.16 of the purines were eliminated through routes other than derivative excretion in urine. Once excretion exceeded 0.6 mmol/kg W0.75 per d, endogenous excretion was effectively zero and thus Y = 0.84 X. In normally fed sheep, derivative excretion should therefore relate to the microbial purines and, hence, microbial protein absorbed according to these models. The changing proportions of allantoin and other derivatives in urine were probably due to changes in the relative importance of endogenous and exogenous purines as precursors. PMID- 2317475 TI - The effect of lactulose, pectin, arabinogalactan and cellulose on the production of organic acids and metabolism of ammonia by intestinal bacteria in a faecal incubation system. AB - An in vitro faecal incubation system was used to study the metabolism of complex carbohydrates by intestinal bacteria. Homogenates of human faeces were incubated anaerobically with added lactulose, pectin, the hemicellulose arabinogalactan, and cellulose, both before and after subjects had been pre-fed each carbohydrate. Fermentation of added substrate was assessed by the production of short-chain fatty acids (SCFA) and suppression of net ammonia generation over 48 h of incubation. Control faecal homogenates to which carbohydrate was not added yielded an average increment of SCFA of 43 mmol/l, equivalent to 172 mmol/kg in the original stool. The addition of lactulose, pectin and arabinogalactan each increased the yield of SCFA by a similar amount, averaging 6.5 mmol/g carbohydrate or 1.05 mol/mol hexose equivalent; organic acid yield was not increased by pre-feeding these substances for up to 2 weeks. Acetate was the major SCFA in all samples at all times and, after pre-feeding with extra carbohydrate, butyrate concentrations exceeded propionate in all samples. Faecal homogenates incubated with cellulose showed no greater SCFA production than controls over the first 48 h, but there was a slight increase when samples from two subjects pre-fed cellulose were incubated for 14 d. Net ammonia generation was markedly suppressed by addition of lactulose to faecal incubates with an initial period of net bacterial uptake of ammonia. Pectin and arabinogalactan also decreased ammonia generation, but the reductions were not significant unless subjects were pre-fed these materials; cellulose had no effect on ammonia generation. PMID- 2317476 TI - Tryptophan metabolism in vitamin B6-deficient mice. AB - Vitamin B6 deficiency was induced in mice by maintenance for 4 weeks on a vitamin B6-free diet. Tryptophan metabolism was assessed by determining the urinary excretion of tryptophan metabolites, the metabolism of [14C]tryptophan in vivo and the formation of tryptophan and niacin metabolites by isolated hepatocytes. The vitamin B6-deficient animals excreted more xanthurenic acid and 3 hydroxykynurenine, and less of the niacin metabolites N1-methyl nicotinamide and methyl-2-pyridone-4-carboxamide, than did control animals maintained on the same diet supplemented with 5 mg vitamin B6/kg. After intraperitoneal injection of [14C]tryptophan, vitamin B6-deficient mice showed lower liberation of 14CO2 from [methylene-14C]tryptophan and [U-14C]tryptophan than did controls, indicating impairment of kynureninase (EC 3.7.1.3) activity. There was no difference between the two groups of animals in the metabolism of [ring-2-14C]tryptophan. Hepatocytes isolated from the vitamin B6-deficient animals formed more 3 hydroxykynurenine and xanthurenic acid than did cells from control animals, but also formed more NADP and free niacin. PMID- 2317477 TI - The nutrition of microbes and man. PMID- 2317478 TI - The effect of diets adequate and deficient in calcium on blood pressures and the activities of intestinal and kidney plasma membrane enzymes in normotensive and spontaneously hypertensive rats. AB - Basolateral and brush-border membranes were prepared from the intestines and kidneys of spontaneously hypertensive (SHR) and normotensive (WKY) rats fed on a calcium-adequate diet and assayed for their enzyme activities. In intestinal basolateral membranes the activities of Na+ K(+)-ATPase (EC 3.6.1.37) Ca2(+) ATPase (EC 3.6.1.38) and alkaline phosphatase (EC 3.1.3.1) were lower in SHR rats when compared with WKY rats, whilst 5'-nucleotidase (EC 3.1.3.5) (a marker for basolateral membranes) was unaffected. In kidney basolateral membranes all enzymes were similar in activity in SHR and WKY rats. In intestinal brush-border membranes the activities of Ca2(+)-ATPase and alkaline phosphatase were lower in SHR rats when compared with WKY rats, whilst microvillus aminopeptidase (EC 3.4.11.2) (a marker for brush-border membranes) was unaffected. In kidney brush border membranes all enzymes were similar in activity in SHR and WKY rats. The blood pressures of the SHR rats were considerably higher than those of the WKY rats. When SHR rats were fed on a Ca-deficient diet the activities of Na+K(+) ATPase, Ca2(+)-ATPase and alkaline phosphatase in basolateral membranes and Ca2(+)-ATPase and alkaline phosphatase in brush-border membranes were all increased in the intestine when compared with SHR rats fed on a Ca-adequate diet. The equivalent enzymes in the kidneys of SHR rats, and the intestines and kidneys of WKY rats, were not affected by altering the Ca in the diet. The blood pressures of SHR rats fed on a Ca-deficient diet were higher than in those fed on a Ca-adequate diet. Blood pressures of WKY rats were not affected by altering the diet in this way. The results indicate that the absorption of Ca by active mechanisms may be reduced in SHR rats compared with WKY rats. Changing the level of Ca in the diet modified both blood pressure and the activities of enzymes which catalyse active Ca transport. The implications of these results to the aetiology, and possible nutritional treatment, of essential hypertension are discussed. PMID- 2317479 TI - Forms of soluble iron in mouse stomach and duodenal lumen: significance for mucosal uptake. AB - Stomach contents of mice fed on a standard rodent breeding diet contained 29-733 microM-soluble nonhaem-iron. A very variable percentage (3-100, mean 49.3 (SE 4.7), n 37) of this Fe was rapidly (half-life less than 1-2 s) available for chelation by the strong Fe(II) chelator ferrozine, with little or no further Fe being available on addition of ascorbate. Ferrozine-available Fe could be detected in the duodenal lumen at concentrations up to 60 microM in vivo and after in vitro neutralization of stomach contents. No significant changes in quantity of stomach ferrozine-available Fe or soluble non-haem-Fe occurred in mice with adaptive enhancement of Fe absorption induced by chronic hypoxia. Electron paramagnetic resonance (e.p.r.) spectroscopy of the soluble portion of mouse stomach contents demonstrated a g = 4.3 signal (rhombic Fe(III)) equivalent to up to 20% of soluble non-haem-Fe. The signal was unaffected by addition of excess ferrozine and increased on subsequent neutralization, suggesting redistribution of Fe from other e.p.r.-silent species. Solutions of Fe nitrilotriacetate (NTA) (a synthetic Fe chelate used as a bioavailable, model Fe solution) were found to contain both rapidly and slowly ferrozine-available Fe (after addition of ascorbate) depending on pH, NTA:Fe ratio and the presence of Ca(II) ions. Fe-ascorbate mixtures (a model solution for Fe absorption studies) also contained ferrozine-available Fe. These results suggest the presence of Fe(II), rhombic Fe(III) and other e.p.r.-silent Fe species in the soluble fraction of mouse stomach contents. The ferrozine-available (Fe(II)) fraction is not limited by the reducing power in the diet, but by binding to ligands. Neutralization with bicarbonate leads to a loss of ferrozine-available Fe and increase in rhombic Fe(III) at the expense of both ferrozine-available and other e.p.r.-silent Fe species. The ferrozine-available Fe in mouse stomach and duodenal lumen can be related to Fe species present in model solutions used for in vitro studies of mucosal uptake mechanisms. PMID- 2317480 TI - Breast milk zinc and copper concentrations in Bangladesh. AB - Breast-fed infants in Bangladeshi villages were weighed at 1, 2, 6, 9 and 12 months. The concentrations of zinc and copper in the breast milk were measured and the daily intake of these elements calculated. Breast milk Zn concentration decreased over the year but was comparable with that found in developed countries. The calculated daily intake decreased from 17.7 to 8.0 mumol (10-30% of recommended dietary allowances (RDA); National Academy of Sciences, 1980). Breast milk Cu concentration also fell over the year and was lower than that reported from developed countries. Calculated daily Cu intake was 1.95-2.63 mumol (RDA 7.81-15.63 mumol). Deficiencies of trace elements may therefore be a problem in poorly nourished communities where breast feeding is continued for several years with only small amounts of additional food. Breast milk may not be adequate as the only source of infant nutrition after the first few months of life in Bangladesh. PMID- 2317481 TI - Ontogenic changes in hepatic glutathione and metallothionein in rats and the effect of a low-sulphur-containing diet. AB - Metallothionein contains about 30% cysteine and is a major protein in newborn rat liver. This protein and glutathione constitute two major intracellular cysteine pools in newborn rat liver. When pregnant rats were fed on a soya-bean-protein diet, low in sulphur amino acids, the hepatic glutathione levels of the dams were decreased. However, this did not affect the levels of glutathione or metallothionein in the pups. The activity of the glutathione-degrading enzyme gamma-glutamyltransferase (EC 2.3.2.2) in the livers of pups was maximum at birth and gradually decreased with age when the hepatic glutathione was transported to the kidney. In the pups born from dams fed on soya-bean-protein diet the decline in the hepatic enzyme activity was delayed, suggesting a continued degradation of glutathione in the liver. These results suggest that even with a maternal nutritional deficiency of sulphur amino acids, the transfer of cysteine to the fetus is not impaired. However, the hepatic intra-organ degradation of glutathione is continued in these pups for a prolonged period after birth compared with pups born from control mothers. The increased degradation of glutathione in the liver may be essential to meet the requirement of cysteine in pups born from dams fed on the soya-bean-protein diet. PMID- 2317482 TI - Age-related changes in the activity of the pyruvate carrier and in the lipid composition in rat-heart mitochondria. AB - The effect of aging on the activity of the pyruvate translocator and on the lipid composition in rat-heart mitochondria has been investigated. It has been found that the rate of pyruvate transport in mitochondria from aged rats (28 months old) is markedly reduced (38%) as compared with that obtained with mitochondria from young adults rats (4 months old). Kinetic analysis of the pyruvate transport shows that only the Vmax of this process is decreased, while there is no change in the Km values. The age-related decrement in the activity of the pyruvate carrier is not due to a decrease in the transmembrane delta pH value, neither does it depend on a decrease in the total number of the pyruvate carrier molecules, titrated with radioactive alpha-cyanocinnamate. The lower activity of the pyruvate translocator in mitochondria from aged rats is associated to a parallel decrement of the rate of pyruvate-dependent oxygen uptake. There is, however no appreciable difference in either the respiratory control ratios or in the ADP/O ratios between these two types of mitochondrion. The Arrhenius plot characteristics differ for pyruvate transport activity in mitochondria from aged rats as compared with young rats in that the break point of the biphasic plot is shifted to a higher temperature. The heart mitochondrial lipid composition is significantly altered in aged rats. The total cholesterol increases (43%), the phospholipids decrease (15%) and the cholesterol/phospholipid molar ratio increases (68%). Among phospholipids, cardiolipin shows the greatest alteration (28% decrease in aged rats). The lower activity of the pyruvate carrier in mitochondria from aged rats may be ascribed to changes in the lipid domain surrounding the carrier molecule in the membrane. PMID- 2317483 TI - Effects of hypoxia and fatty acids on the distribution of metabolites in rat heart. AB - The effects of exogenous fatty acids and hypoxia on cardiac energy metabolism were studied by measuring mitochondrial and cytosolic adenine nucleotides as well as CoA and carnitine esters using a tissue fractionation technique in non-aqueous solvents. During normoxia, the administration of 0.5 mM palmitate caused a considerable increase in acyl-CoA and acylcarnitine, particularly in mitochondria. High-energy phosphates, however, were only slightly altered. A 90 min low-flow hypoxia caused a dramatic increase in mitochondrial acyl esters. The mitochondrial ATP content decreased significantly, while the cytosolic concentration was only slightly diminished, suggesting an inhibition of mitochondrial adenine nucleotide translocation by long-chain acyl-CoA. Addition of palmitate during hypoxia amplified hypoxic damage and reduced adenine nucleotides in both compartments considerably, while fatty acid metabolites were only slightly affected. In presence of an inhibitor of fatty acid oxidation (BM 42.304), the fatty-acid-induced acceleration of cardiac injury was prevented. Since BM 42.304 decreased mitochondrial acylcarnitine and increased the cytosolic concentration significantly, BM 42.304 was presumed to inhibit mitochondrial acylcarnitine translocase. However, a causal relationship between lipid metabolites and ischemic damage seemed unlikely. PMID- 2317484 TI - Significance and redox state of SH groups in pyruvate carrier isolated from bovine heart mitochondria. AB - The role and properties of -SH groups of purified pyruvate (monocarboxylate) carrier were investigated. After isolation, this protein has all -SH groups in the oxidized state. Upon reduction, the carrier can be labelled with eosin-5 maleimide. The shift in apparent Mr after the labelling points to the presence of at least two cysteine residues. Pyruvate uptake in the reconstituted system is inhibited by both permeable (eosin-5-maleimide at 1 mM concentration) and impermeable (mersalyl, p-chloromercuribenzoate) -SH group reagents. Phenylarsine oxide inhibits pyruvate transport only slightly (20%), but the inhibition is enhanced after preincubation with the substrate. PMID- 2317485 TI - Structure of polymerizable lipid bilayers: water profile of a diacetylenic lipid bilayer using elastic neutron scattering. AB - Elastic neutron scattering experiments have been used to study the hydration of multibilayers of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC). Previously published FTIR spectroscopic data had suggested, based on shifts in the carbonyl (C = O) stretch frequencies, that the phosphocholine headgroup in these polymerizable lipid bilayers was much less hydrated than that of saturated phosphatidylcholines. Our results demonstrate that the DC8,9PC headgroup is at least as well hydrated as that of dipalmitoylphosphatidylcholine (DPPC), a saturated lipid, under the same conditions. PMID- 2317486 TI - pH-sensitive, plasma-stable liposomes with relatively prolonged residence in circulation. AB - Acid-sensitive liposomes composed of unsaturated phosphatidylethanolamine (PE) are efficient vehicles for cytoplasmic delivery of the target cells. We have recently shown that liposomes composed of dioleoyl-PE (DOPE) and dipalmitoyl succinylglycerol (DPSG) retain the acid-sensitivity after exposure to human plasma. In the present work, we have extended these observations to investigate the role of ganglioside GM1 on the blood residence time of these liposomes. Small (d approximately 100 nm) unilamellar liposomes composed of DOPE and DPSG (4:1, molar ratio) became progressively less acid-sensitive when increasing amounts of GM1 were included in the lipid composition. However, partial sensitivity to acid (40-50% release of entrapped contents at pH 4) could be retained up to 5% GM1, even for liposomes which had been exposed to human plasma. Inclusion of GM1 in the lipid composition only slightly increased the release of entrapped contents in the presence of human plasma. The biodistribution of i.v. injected GM1 containing liposomes was studied by following the entrapped 125I-labeled tyraminylinulin marker in Balb/c mice. Inclusion of up to 5% GM1 showed a transient increase in the blood level and a concomitant decrease of liver and spleen uptake of liposomes. Thus, these liposomes are pH-sensitive, plasma-stable and show a relatively prolonged residence time in circulation. They are potentially significant drug carriers in vivo. PMID- 2317487 TI - Effect of the level of ATP and of the state of spectrin on osmotic properties of bovine erythrocytes. AB - The effect of the intracellular level of ATP and of the state of spectrin on the critical cell volume of bovine erythrocyte was studied. The state of spectrin was changed by thermal denaturation, which for the bovine red cell took place at similar temperature as for the human erythrocyte. The increase of the ATP level and the spectrin denaturation increased the critical cell volume, while metabolic starvation decreased it. The changes of the ATP level did not influence the critical volume after the denaturation of spectrin. The results suggest that the ATP-dependent effect on the critical cell volume was caused by an alteration of the membrane extensibility due to the change of the membrane skeleton-lipid bilayer interaction(s). PMID- 2317489 TI - Reversible large-scale deformations in the membranes of electrically-treated cells: electroinduced bleb formation. AB - Morphological changes in electrically-treated cells have been investigated by light and scanning electron microscopy. The application of 100-microseconds rectangular pulses of 1.3 kV/cm electric field to different types of cells (FBT, MEF, RAT-1, L-cells) in the physiological medium leads to the formation and growth of spherical and hemispherical protuberances of the cell membrane. The formation of such electroinduced blebs is not associated with the cells' death and is reversible. The electroinduced blebs are mainly formed at those sites of the cell membrane which are subjected to the highest voltage during the electric pulses. Increasing the tonicity of the medium by introducing 20 mM of inulin prevents the bleb formation, indicating the osmotically-dependent nature of the processes involved. When electric pulses are applied to the cells pre-treated with cytochalasin B, the formation of electroinduced blebs occurs independently from cytochalasin-induced ones originally present on such cells. Speculations are presented concerning the nature of the membrane structural changes underlying the electroinduced blebbing and their possible role in some electrically-induced processes. PMID- 2317488 TI - Composition of the inner mitochondrial membrane of porcine corpus luteum. AB - An inner mitochondrial membrane fraction was prepared from porcine corpus luteum. The concentrations of the respiratory cytochromes, cytochrome P-450scc, cholesterol, ubiquinone, cardiolipin and the total phospholipids were measured. The fatty acid compositions of cardiolipin and the total phospholipid fraction were determined. Comparative data from porcine heart and liver were obtained using the same methods. Differences in both the concentration and the fatty acid composition of the phospholipids were observed between the tissues. It appeared that the phospholipid bilayer was expanded relative to haem a in luteal mitochondria. It is proposed that in the ovary this expansion may be necessary to accommodate cytochrome P-450scc and its substrate, cholesterol. PMID- 2317490 TI - Interaction of cyclosporin A with dipalmitoylphosphatidylcholine. AB - Cyclosporin A, a hydrophobic cyclic peptide, is a potent immunosuppressant. In an attempt to determine the localization of cyclosporin A in phospholipid membranes, the effect of cyclosporin A on dipalmitoylphosphatidylcholine (DPPC) has been investigated using deuterium nuclear magnetic resonance (2H-NMR) spectroscopy and differential scanning calorimetry (DSC). Cyclosporin A was dispersed within acyl chain per-deuterated DPPC at a concentration of 6 mole percent, hydrated with buffer, and the spectra obtained over a range of temperatures were compared with that of pure DPPC. The changes caused by cyclosporin A were assessed by the first moment (M1) and order parameters calculated from the spectra. The presence of cyclosporin A decreases the magnitude of M1 at temperatures below the gel to liquid-crystalline phase transition temperature but increases M1 at temperatures above the transition. In addition, the change in M1 at the transition temperature was also less abrupt when cyclosporin A was present. For bilayers in the liquid crystalline state, cyclosporin A causes an increase in the order parameters along the acyl chains which suggests that cyclosporin A is located along the acyl chains of the phospholipid. For DSC, cyclosporin A was dispersed in non deuterated DPPC at different peptide to phospholipid mole ratios. The endothermic peaks associated with the gel to liquid-crystalline phase transition and pretransition were recorded and compared with similar mole ratios of cholesterol to lipid. At 30 mole percent cyclosporin A, small decreases in the main transition temperature and associated enthalpy were observed, whereas at 30 mole percent cholesterol, the main transition is barely distinguishable from the baseline. The pretransition was not observed with the addition of 11 mole percent of either cyclosporin A or cholesterol. The results of the thermal analysis indicate that although cyclosporin A and cholesterol appear to be both located along the acyl chains of the phospholipids, they have dramatically different interactions with the membrane lipids. PMID- 2317491 TI - Interactions of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. AB - Several novel cationic amphiphiles, based on a hydrophobic cholesteryl or dioleoylglyceryl moiety, have been prepared whose hydrophobic and cationic portions are linked by ester bonds to facilitate efficient degradation in animal cells. Dispersions combining such cationic species with phosphatidylethanolamine (PE), certain structural analogues of PE or diacylglycerol can mediate efficient transfer of both nonexchangeable lipid probes and the DNA plasmid pSV2cat into cultured mammalian (CV-1 and 3T3) cells. The abilities of different types of cationic lipid dispersions to mediate transfection of mammalian cells with pSV2cat could not be directly correlated with their abilities to coalesce with other membranes, as assessed by their ability to intermix lipids efficiently with large unilamellar phosphatidylcholine/phosphatidylserine vesicles in the presence or absence of DNA. The cytotoxicities toward CV-1 cells of dispersions combining PE with most of the degradable cationic amphiphiles studied here compare favorably with those reported previously for similar dispersions containing other types of cationic amphiphiles. Fluorescent analogues of two of the diacylglycerol based cationic amphiphiles examined in this study are shown to be readily degraded after incorporation into CV-1 cells from PE/cationic lipid dispersions. PMID- 2317492 TI - Liposomes with entrapped doxorubicin exhibit extended blood residence times. AB - The blood residence time of liposomes with entrapped doxorubicin is shown to be significantly longer than for identically prepared empty liposomes. Liposomal doxorubicin systems with a drug-to-lipid ratio of 0.2 (w/w) were administered at a dose of 100 mg lipid/kg. Both doxorubicin and liposomal lipid were quantified in order to assess in vivo stability and blood residence times. For empty vesicles composed of phosphatidylcholine (PC)/cholesterol (55:45, mole ratio) and sized through filters of 100 nm pore size, 15-25% of the administered lipid dose was recovered in the blood 24 h after i.v. injection. The percentage of the dose retained in the circulation at 24 h increased 2-3-fold when the liposomes contain entrapped doxorubicin. For 100 nm distearoyl PC/chol liposomal doxorubicin systems, as much as 80% of the injected dose of lipid and drug remain within the blood compartment 24 h after i.v. administration. PMID- 2317493 TI - Reconstitution of sulfobromophthalein transport in erythrocyte membranes induced by bilitranslocase. AB - Bilitranslocase, the protein responsible for the anion translocation at the sinusoidal plasma membrane level in liver, was shown to be able to reconstitute the transport of sulfobromophthalein in liposomes in the past. The protein preparation used in those experiments consisted of two subunits of 35.5 and 37 kDa. The isolated 37 kDa protein, when inserted in erythrocyte membrane vesicles, confers to the particles the ability to carry out an electrogenic transport of sulfobromophthalein. The effect is specific and can be inhibited by monospecific polyclonal antibodies raised against the protein. In may be concluded that the 37 kDa protein band, present in previous preparations of bilitranslocase, is not only a necessary but also a sufficient component of the transport system for bilirubin and functional analogues. PMID- 2317494 TI - Partitioning behavior of indocarbocyanine probes between coexisting gel and fluid phases in model membranes. AB - Gel-fluid partition coefficients, Kp, were measured for a series of indocarbocyanine dyes in multilamellar lipid vesicles. The dyes examined had alkyl chain lengths from 12 to 22 carbons. Fluorescence quenching by a spin labeled phosphatidylcholine-enriched fluid phase created a large difference in quantum yield for indocarbocyanine fluorescence between fluid and gel phases, enabling reliable Kp determinations. The values range from Kp = 8 for the 12 carbon chain, favoring a fluid phase over a Ca2-phosphatidylserine rigid phase, to Kp = 0.02 for the 20-carbon chain dye, favoring a distearoylphosphatidylcholine-rich gel phase over the fluid phase. PMID- 2317495 TI - Iturin lipopeptides: interactions of mycosubtilin with lipids in planar membranes and mixed monolayers. AB - The interactions between the antifungal lipopeptide mycosubtilin and lipids are studied. Mycosubtilin increases the ion permeability of planar lipid membranes by forming ion conducting pores. The lifetime of these pores is greatly increased when the membrane contains cholesterol. In mixed monolayers the interaction between mycosubtilin and DMPC leads to the formation of a mycosubtilin/DMPC 1:2 complex non miscible in the excess DMPC monolayer but miscible in the mycosubtilin monolayer. Mycosubtilin and cholesterol interact strongly in monolayers in all proportions and form a mycosubtilin-cholesterol (1:2) complex. These results are analyzed with reference to the overall view of the activity of iturins and the importance of the lipopeptide conformation is outlined. PMID- 2317496 TI - The effect of transmembrane potential on the dynamic behavior of cell membranes. AB - The relationship between transmembrane potential and lipid dynamics in the cytoplasmic membrane of mouse thymus cells has been investigated. Changes of transmembrane potential was followed by measuring the fluorescence emission of the anionic dye, bis-(1,3-dibutylbarbiturate)trimethine oxonol (diBa-C4-(3)). Assessment of lipid fluidity was carried out applying three fluorescent lipid probes, 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), 12 (9-anthroyloxy)stearic acid (12-AS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) used to monitor different structural regions of the bilayer. The fluorescence anisotropy of these probes was measured as a function of temperature at two values of transmembrane potential. In the case of DPH it proved to depend on the membrane potential in the higher temperature range (above 28 degrees C), while no such a dependence could be observed for DPH below this temperature range and for TMA-DPH and 12-AS in between 20 and 37 degrees C. These data suggest that changes in transmembrane potential are accompanied with some local alteration in membrane lipid dynamics and/or structure. PMID- 2317497 TI - Na+ and pH dependence of 5-methyltetrahydrofolic acid and methotrexate transport in freshly isolated hepatocytes. AB - The dependence of the high-affinity transport systems for 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) and methotrexate on sodium ions and on pH was examined in freshly isolated rat hepatocytes. Previous studies indicated that transport of these folate derivatives was sodium-dependent. Experiments to determine the Km for sodium of 5-CH3-H4PteGlu transport showed no dependence on extracellular sodium. However, uptake was sodium-dependent when hepatocytes were preincubated for 30 min in sodium-free medium, a treatment which resulted in an increase in the transmembrane pH gradient (delta pH = pH out-pH in) and a decrease in the uptake of 5-CH3-H4PteGlu. Uptake of methotrexate displayed a linear dependence on extracellular sodium ions. Uptake of 5-CH3-H4PteGlu increased linearly as the transmembrane pH gradient decreased; i.e., as the medium became more acid with respect to the cytosol. Lineweaver-Burk and Scatchard plots of 5-CH3-H4PteGlu uptake indicated an apparent Km for H+ of about 24 nM, equivalent to a pH of 7.6. Hill-plots suggested a stoichiometry of 1:1 for the interaction of protons with the 5-CH3-H4PteGlu transport system. Both the Km and Vmax for 5-CH3-H4PteGlu transport were increased at pH 5.5 compared to pH 7.4, suggesting that extracellular protons increased the number of and/or the activity of the membrane carrier. In contrast, methotrexate transport was maximal at pH 7 where the transmembrane pH gradient was zero. These results suggest the possibility that 5 CH3-H4PteGlu may be cotransported along with H+ ions in hepatocytes, although they do not rule out a 'catalytic coupling' whereby protons interact with the carrier to stimulate substrate flux without concomitant H+ transport. PMID- 2317498 TI - Membrane skeleton-bilayer interaction is not the major determinant of membrane phospholipid asymmetry in human erythrocytes. AB - Transbilayer phospholipid distribution, membrane skeleton dissociation/association, and spectrin structure have been analysed in human erythrocytes after subjecting them to heating at 50 degrees C for 15 min. The membrane skeleton dissociation/association was determined by measuring the Tris induced dissociation of Triton-insoluble membrane skeletons (Triton shells), the spectrin-actin extractability under low ionic conditions, and the binding of spectrin-actin with normal erythrocyte membrane inside-out vesicles (IOVs). The spectrin structure was ascertained by measuring the spectrin dimer-to-tetramer ratio as well as the spectrin tryptophan fluorescence. Both the Tris-induced Triton shell dissociation and the spectrin-actin extractability under low ionic conditions were considerably reduced by the heat treatment. Also, the binding of heated erythrocyte spectrin-actin to IOVs was significantly smaller than that observed with the normal cell spectrin-actin. Further, the quantity of spectrin dimers was appreciably increased in heat-treated erythrocytes as compared to the normal cells. This change in the spectrin dimer-to-tetramer ratio was accompanied by marked changes in the spectrin tryptophan fluorescence. In spite of these heat induced alterations in structure and bilayer interactions of the membrane skeleton, the inside-outside glycerophospholipid distribution remained virtually unaffected in the heat-treated cells, as judged by employing bee venom and pancreatic phospholipase A2, fluorescamine and Merocyanine 540 as the external membrane probes. These results strongly indicate that membrane bilayer-skeleton interaction is not the major factor in determining the transbilayer phospholipid asymmetry in human erythrocyte membrane. PMID- 2317499 TI - The determination of binding site density and association constants for monovalent cation adsorption onto liposomes made from mixtures of zwitterionic and charged lipids. AB - The Gouy-Chapman-Stern theory predicts that the shape (but not the magnitude) of the surface potential dependence on the electrolyte concentration mainly reflects the screening of the surface charge but not cation adsorption. So this dependence does not allow to determine two parameters of the theory (the surface density of binding sites (S) and the association constant (K)) simultaneously. Therefore the fitting procedure for the determination of S and K was suggested as a test of cation adsorption for the surface or zeta potential measurements at a fixed electrolyte concentration but with a variable ratio of charged and neutral components in the lipid mixture. This procedure was applied to the electrophoretic measurements made by the method of photon correlation spectroscopy in the suspensions of PS/PC or CL/PC liposomes in the monovalent electrolytes. For KCl and NaCl electrolytes it only leads to the different association constants (about 0.2 and 0.8 M-1, respectively) corresponding with data from the literature but to the same value of the surface charge density (about -16 microC/cm2) which is smaller than usually postulated for PS membranes. The fitting of zeta potentials measured in tetraalkylammonium salts shows a small cation adsorption but a large surface charge density (about -21 microC/cm2). PMID- 2317500 TI - Subcellular distribution of selenoproteins in the liver of the rat. AB - After in vivo labeling with [75Se]selenite, the intracellular distribution of selenoproteins in the liver was investigated in selenium-adequate and selenium deficient rats. In the subcellular fractions, which were obtained by differential centrifugation, the proteins were separated by means of SDS-PAGE and the selenium compounds were identified via their 75Se activity. In this way twelve selenium containing proteins or protein subunits with molecular weights between 12,100 and 75,400 were found. Glutathione peroxidase was concentrated in the cytosol and in the mitochondria. With the newly detected selenoproteins, some were enriched in the cytosol, one was mainly found in the nuclear fraction and some, which were present mainly in the mitochondrial and microsomal fractions, are most probably membrane-bound. In the liver of selenium-depleted rats the selenium administered was used predominantly to restore the levels of some of the newly found selenoproteins, while in the liver of selenium-adequate animals most of the selenium retained was incorporated into the glutathione peroxidase. The differences in the distribution among the subcellular fractions and the specific incorporation of the element in selenium deficiency into certain compounds suggest that there are several metabolic pathways for selenium and that the selenoproteins are involved in several different processes of intracellular metabolism. PMID- 2317501 TI - Variability of proteoglycan expression in the isolated rat glomerulus. AB - The sulphation of proteoglycans in freshly isolated rat glomeruli was studied by biosynthetic labelling with [35S]sulphate. At least 75% of the observed sulphation requires de novo synthesis of core protein and proceeds at a constant rate over at least 40 h. Heparan and dermatan sulphate proteoglycans (HSPG and DSPG, respectively) are the two major species produced, with only minor amounts (less than 5%) of chondroitin sulphate labelled under these conditions. Several factors affect the population distribution of labelled material. When glomeruli were obtained from rats 6 weeks of age, HSPG accounted for 75 +/- 9% of tissue proteoglycan sulphated over 16 h. When older rats (12-14 weeks) were used, only 32 +/- 10% of label was associated with HSPG, DSPG accounting for the remainder. Production of HSPG is sulphate-dependent, increasing relative to DSPG with increasing sulphate, up to physiological concentrations. However, the net charge density of sulphated material is conserved even at the lowest concentrations of sulphate. This may reflect the importance of electrostatic properties in the function of glomerular proteoglycans. The production of HSPG increases relative to DSPG with time following isolation and this effect is more dramatic in glomeruli from younger rats. However, reciprocal changes in production of HSPG and DSPG sustain a constant rate of sulphation. This phenomenon may arise from interdependency of the glomerular epithelial and mesangial cells with respect to regulation of proteoglycan synthesis. PMID- 2317502 TI - Increased intestinal iron absorption in rats with normal hepatic iron stores. Kinetic aspects of the adaptative response to parenteral iron repletion in dietary iron deficiency. AB - Male Sprague-Dawley rats were fed an iron-deficient diet for 8 days. After this period, iron stores were repleted in three groups of animals by intravenous administration of iron dextran. In a second set of experiments, iron was administered in the same dose as Fe nitrilotriacetic acid complex. 12 h, 24 h and 48 h thereafter, the intestinal iron transfer in vitro and in vivo as well as the non-heme iron and ferritin content were determined in both the liver and the jejunal mucosa. In iron deficiency, intestinal iron transfer is increased to 230% of untreated controls, while non-heme iron and ferritin decreased to 20% and 10% in the liver and to 55% and 25% in the mucosa, respectively. 12 h and 24 h after parenteral administration of 0.1 mmol Fe/kg body weight iron transfer was as high as in iron deficiency, while liver iron stores were not significantly different from the untreated controls. In this situation, the close link between decreases in body iron stores and increases in iron transfer was temporarily dissociated. This can be related to the time lag between the incorporation of parenterally applied iron in the liver and in the jejunal mucosa. The data provide evidence for the hypothesis that the hepatic iron stores have no means of neural or hormonal communication with the small intestine in order to adapt iron transfer to their state of repletion on short notice. Intestinal iron transfer returned to control levels after 48 h. PMID- 2317503 TI - Reactivity of sulfhydryl groups in the brush-border membranes of chick duodena is increased by 1,25-dihydroxycholecalciferol. AB - The total amount and reactivity of SH-groups were determined in isolated duodenal brush-border membranes from rachitic chicks given 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3) before isolation of the membranes. 1,25(OH)2D3 treatment significantly increased the total amount of SH groups (9.7 +/- 2.3 vs. 23.9 +/- 2.1, P less than 0.001, n = 6) in brush-border membranes solubilized in 1% sodium dodecyl sulfate. The rate of reaction (reactivity) of membrane-bound SH-groups, determined with the fluorescent thiol reagent, N-(7-dimethylamino-4 methylcoumarin-3-yl)maleimide (DACM), was also significantly enhanced by the intravenous injection of various doses (0.005-0.10 microgram) of 1,25(OH)2D3 into vitamin D-deficient chicks. An increase in reactivity occurred as early as 10 min after dosing of the chicks with 1,25(OH)2D3. Fluorescence scanning of the membrane proteins labeled with DACM and separated by polyacrylamide gel electrophoresis revealed three major peaks of fluorescence and a generally higher degree of fluorescent labeling of these and many other proteins in the membranes isolated from the 1,25(OH)2D3-treated chicks. The physiological significance of the 1,25(OH)2D3-mediated increase in the reactivity and total amount of membrane bound SH-groups in terms of vitamin-D-dependent epithelial transport and epithelial membrane properties needs to be further explored. PMID- 2317505 TI - Metabolic control of the expression of mitochondrial D-beta-hydroxybutyrate dehydrogenase, a ketone body converting enzyme. AB - The effects of various metabolic conditions inducing an overproduction of ketone bodies in the rat were studied at different levels of D-beta-hydroxybutyrate dehydrogenase expression, i.e., enzymatic activity and protein content in purified mitochondria, and translational activity of isolated free cytosolic polysomes. The strongest variations were obtained in diabetes mellitus where the D-beta-hydroxybutyrate dehydrogenase expression is largely decreased. Insulin can reverse this strong effect. Modulation of liver enzyme activity and of enzyme content was observed under the other conditions tested, i.e., a decrease and an increase in starvation and hyperlipidemic conditions, respectively. A comparative study was carried out on the enzyme of extrahepatic tissues, i.e., heart, kidney and brain. The results indicate that the D-beta-hydroxybutyrate dehydrogenase function appears to be controlled, at least at the translational, post translational and catalytic levels. PMID- 2317504 TI - The sex difference in the regulation of liver regeneration after partial hepatectomy in the rat. AB - The increases in the activity of hepatic thymidylate synthetase and thymidine kinase, which catalyzes the formation of thymidylate via the de novo and salvage pathways, respectively, were significantly suppressed 24 h after 70% partial hepatectomy in female rats administered either alpha- or beta-adrenoreceptor antagonists. The injection of beta-antagonist to male or ovariectomized female rats had no effect on the activities of these enzymes. Only alpha-adrenoceptor antagonist depressed these enzymatic activities of 24-h-regenerating liver in male and ovariectomized female rats. The decrease of the activities of thymidylate synthetase and thymidine kinase was accompanied by a concomitant reduction of DNA content in 24-h-regenerating liver. It is concluded that catecholamine regulates the female rat liver regeneration through both alpha- and beta-adrenergic pathways by the inductions of thymidylate synthase and thymidine kinase, while in adult male and ovariectomized female rats, only the alpha mediated pathway is involved. PMID- 2317506 TI - Heat conduction microcalorimetry of overall metabolism in rabbit alveolar macrophages in monolayers and in suspensions. AB - A technique has been developed for studying the overall metabolism in small numbers of cells in monolayers and in suspensions by measuring the heat exchange rate with a thermopile heat-conduction microcalorimeter. The system was tested with alveolar macrophages from rabbits, and heat flux-time curves could be monitored from numbers of cells as low as 0.05 . 10(6). The metabolic activity was found to be unchanged or to decrease very slowly over a period of 20 h. In a conventional cell medium, without the addition of serum, a mean heat flux value of 19.4 (S.D. 3.2) pW. cell-1 (37 degrees C, pH = 7.4) was obtained for alveolar macrophages in monolayers. The corresponding value for cells in the same medium, with the addition of 20% homologous rabbit serum, was 27.0 (S.D. 2.0). We suggest that this calorimetric method can be used as a short-term cytotoxic test for measuring potentially toxic agents in our environment; this test can involve alveolar macrophages of either animal or human origin. In such an assay, the cells should be used in monolayers, and suspensions should be avoided. We found that when alveolar macrophages were used in suspension, the metabolic activity, measured as heat flux, was dependent on cell concentration, even at values as low as 0.2. 10(6) cells per ml. PMID- 2317507 TI - The intracellular pH of tunicate blood cells: Ascidia ceratodes whole blood, morula cells, vacuoles and cytoplasm. AB - The intracellular pH of blood cells of the tunicate Ascidia ceratodes has been measured by equilibration of radioactively labeled markers between intra- and extracellular media. Labeled acid, 5,5-dimethyloxazolidine-2,4-dione (DMO), and base, methylamine (MA), have been used in the range of extracellular pH (pHm) of 4.5-7. For unsorted blood cells MA is less sensitive to the transmembrane pH gradient (delta pH) than is DMO in the pHm of 6.3-7. The data measured by DMO yield an intracellular pH value of 6.98 +/- 0.15. Ficoll density gradients separated 86.4% pure morula cells. Other experiments show that morula cells contain significant amounts of vanadium and most of the free tunichrome. Using both MA and DMO with morula cells yields pH values of 5.0 +/- 0.2 for the vacuoles and 7.1 +/- 0.2 for the cytoplasm. If vanadium is accumulated in the intravacuolar solution space, then this mildly acidic pH indicates that the aquo V3+ ion, which is only stable below pH 3, is stabilized by some factor other than high hydrogen ion concentration. This factor may be chelation by tunichrome. It is also possible that accumulated vanadium(III) is sequestered in hydrophobic regions of the vacuolar or cellular membranes. PMID- 2317508 TI - Purification and characterization of bioactive peptides from skin extracts of Rana esculenta. AB - The peptide fraction extracted by methanol from the skin of Rana esculenta, a species widely distributed in Western Europe, was investigated. The pharmacological activity found in the extract is attributable to the presence of authentic bradykinin, together with a shorter, partially active version of this molecule, des-Arg9-bradykinin. Also the bradykinin fragment 1-7 has been isolated, but it was inactive in our bioassay system. Moreover, a family of hydrophobic peptides has been purified and characterized, which appeared devoid of pharmacological activities when tested on smooth muscle preparations, but were provided with hemolytic activities. PMID- 2317509 TI - Monoclonal antibodies directed against a synthetic peptide corresponding to the alpha-bungarotoxin binding region of the acetylcholine receptor. AB - Murine monoclonal antibodies have been produced against a 32 amino acid synthetic peptide corresponding to residues 173-204 on the alpha-subunit of the nicotinic acetylcholine receptor from Torpedo californica. All of the monoclonal antibodies were of the IgM subtype and most cross-reacted with the purified native receptor. None of the antibodies were effective in blocking alpha-bungarotoxin binding to the receptor nor, conversely, did alpha-bungarotoxin interfere with antibody binding. However, two monoclonal antibodies, previously shown to bind near the ligand binding site on the native receptor, did compete partially (50%) with the binding of one of the IgM monoclonal antibodies. PMID- 2317510 TI - The effects of anions on the kinetics of reductive elimination of iron from monoferrictransferrins by thiols. AB - The kinetics of reductive elimination of iron from the human serum monoferric transferrins by thioglycollate (TG), 3-mercaptopropionate (MP), cysteine (Cys), cysteamine (Cym) and 2-mercaptoethanol (ME) have been studied at 37 degrees C using bathophenanthroline sulphonate (BPS) as the ferrous ion acceptor. Analysis of the entire course of the reaction was possible only with thioglycollate since the other thiols cause eventual protein precipitation; in these cases, initial rates were used. The rate of iron release is linearly dependent on thiol concentration at low concentrations of reductant (less than approx. 0.2 M) and increases more rapidly with higher concentrations (up to 0.5-0.75 M). The thiols fall into two distinct groups, with TG, MP and Cys reacting at approx. the same rate, which is an order of magnitude faster than the reaction with Cym and ME. The carboxylate functionality present in the first group may be responsible for the faster reaction rate, by competitively weakening the interaction between the protein and synergistic anion. The pH-dependence of the rate of reductive elimination appears to depend on ionizable functionalities on both the protein and reducing agent. The addition of NaCl, NaClO4, NaHCO3 and Na2HPO4 increases the rate of iron release from the monoferric transferrins. The last two have particularly large accelerating effects and, in the case of the N-terminal monoferrictransferrin, gave saturation kinetics, suggesting that the observed effect is due to conformational changes in the protein caused by binding of ions. The role of the Fe-synergistic anion complex in the transferrins as a 'trapped intermediate' is considered. PMID- 2317512 TI - Binding of inhibitors to the major glutathione S-transferase from bovine brain. Competitive binding between bilirubin and glutathione. AB - The binding of non-substrate ligands to the glutathione S-transferase (RX:glutathione R-transferase, EC 2.5.1.18) from bovine brain has been investigated kinetically by monitoring the inhibition of the enzyme-catalyzed reaction between glutathione and 1-chloro-2,4-dinitrobenzene. Bilirubin, thyroxine, lithocholic acid, retinoic acid and retinol are competitive inhibitors with respect to glutathione. Cooperative binding effects are observed with lithocholic acid, retinoic acid and retinol while cooperative binding is not observed with thyroxine or bilirubin. Bilirubin is the most potent inhibitor with constants of 0.1 and 110 microM. 50% of the total activity is lost upon binding to the high-affinity site and the remainder is lost at higher bilirubin concentrations. In spite of the apparently favorable binding for bilirubin, it is estimated that the high intracellular concentrations of reduced glutathione will saturate the enzyme and allow only a small fraction of the bilirubin in brain to bind to the enzyme. It is concluded that the binding of these ligands may be of minor importance in vivo. PMID- 2317511 TI - A physical characterization of sulfane sulfurtransferase. AB - The bacterial enzyme sulfane sulfurtransferase has been studied using spectroscopic techniques. The enzyme was characterized in terms of its near-UV absorption spectrum, molar ellipticity, intrinsic fluorescence spectra and the effects of general and ionic quenching reagents upon its fluorescence. Fluorescence model studies are consistent with sulfane sulfurtransferase having only a single tryptophan residue, which accounts for its low UV absorption coefficient and suggested that this residue is at least partially exposed to solvent. Second derivative absorption spectroscopy studies revealed that most of the bacterial enzyme's tyrosine residues are exposed to solvent. Unlike the better known sulfurtransferase, bovine liver rhodanese, sulfane sulfurtransferase does not undergo a detectable increase in quantum yield when shifting from the sulfur-containing covalent enzyme intermediate to the free enzyme form (which lacks sulfur) during catalysis. CD studies suggest that sulfane sulfurtransferase has a significantly higher proportion of alpha-helix than rhodanese. The renaturation of sulfane sulfurtransferase denatured in 6 M guanidine was shown to be rapid and complete provided that the enzyme had not been oxidized while in the denatured state. Sulfane sulfurtransferase, like rhodanese, catalyzes the transfer of sulfur from thiosulfate to cyanide via a persulfide intermediate, and displays remarkably similar kinetics in this process (Aird, B.A., Heinrikson, R.L. and Westley, J. (1987) J. Biol. Chem 262, 17327-17335). In light of this, the results of the structural studies with sulfane sulfurtransferase are compared and contrasted to data from similar experiments with rhodanese in hopes that they would provide insight about which phenomena observed with rhodanese are intrinsic to the process of transferring sulfur atoms. PMID- 2317513 TI - Isolation and partial characterization of a cytochrome P-450 isoenzyme (cytochrome P-450tu) from mouse liver tumors. AB - Experimental hepatomas induced with 5,9-dimethyldibenzo[c,g]carbazole in female XVIInc/Z mice display a strong microsomal steroid 15 alpha-hydroxylation activity. A cytochrome P-450 isoenzyme (cytochrome P-450tu), specific for this activity, has been isolated by an HPLC derived method using various Fractogel TSK and hydroxyapatite supports. On SDS polyacrylamide gel electrophoresis the purified protein appeared as one major band with an apparent Mr of 50,000. Its specific cytochrome P-450 content was 7.55 nmol/mg protein. As deduced from the visible spectrum, the heme iron of the isolated P-450tu was to 72% in the high spin state. The CO-bound reduced form showed an absorption maximum at 450 nm. In addition to the stereospecific 15 alpha-hydroxylation of progesterone (2.3 min-1) and testosterone (2.5 min-1), the enzyme catalyzed also 7-ethoxycoumarin O deethylation, benzphetamine N-demethylation and aniline 4-hydroxylation. Its N terminal amino-acid sequence (21 residues) was identical to that of cytochrome P 450(15) alpha, isolated by Harada and Negishi from liver microsomes of 129/J mice. P-450tu differed from P-450(15) alpha by its higher molecular weight, its 40-times lower steroid 15 alpha-hydroxylation and its 4-times higher benzphetamine N-demethylation. PMID- 2317514 TI - Effect of calcium ion on the dimerization of alpha-chymotrypsin. AB - Results of a sedimentation equilibrium study of the inhibitory effect of calcium ion on the dimerization of alpha-chymotrypsin (pH 3.9, I 0.2) are used to establish that the phenomenon does not reflect increased electrostatic repulsion between Ca2(+)-saturated enzyme molecules, but rather the displacement of the monomer-dimer equilibrium by the specific, weak interaction of metal ion with a single site on monomeric enzyme. PMID- 2317515 TI - Autoxidation of myoglobin from bigeye tuna fish (Thunnus obesus). AB - Native oxymyoglobin (MbO2) was isolated directly from the skeletal muscle of bigeye tuna (Thunnus obesus) with complete separation from metmyoglobin (metMb) on a CM-cellulose column. It was examined for its stability properties over a wide range of pH values (pH 5-12) in 0.1 M buffer at 25 degrees C. When compared with sperm whale MbO2 as a reference, the tuna MbO2 was found to be much more susceptible to autoxidation. Kinetic analysis has revealed that the rate constant for a nucleophilic displacement of O2- from MbO2 by an entering water molecule is 10-times higher than the corresponding value for sperm whale MbO2. The magnitude of the circular dichroism of bigeye tuna myoglobin at 222 nm was comparable to that of sperm whale myoglobin, but its hydropathy profile revealed the region corresponding to the distal side of the heme iron to be apparently less hydrophobic. The kinetic simulation also demonstrated that accessibility of the solvent water molecule to the heme pocket is clearly a key factor in the stability properties of the bound dioxygen. PMID- 2317516 TI - Electron transferase activity of diaphorase (NADH: acceptor oxidoreductase) from Bacillus stearothermophilus. AB - Electrochemical kinetic measurements were carried out for electron-transfer between NADH and the oxidized forms of mediators (ferrocenylmethanol (FMA), ferrocenyl-1-ethanol (FEA), N,N,N',N'-tetramethylphenylenediamine (TMPD), Co(Phen)2+(3) and Fe(CN)4-(6)) catalyzed by diaphorase (NADH: acceptor oxidoreductase, EC 1.6.99.-) purified from Bacillus stearothermophilus. Cyclic voltammograms for the mediators with excess NADH in the presence of diaphorase gave steady-state currents. The quantitative analysis of the dependence of the current on the mediator concentration yielded a Michaelis constant (Km) and molecular activity (ko), which are difficult to determine by the conventional spectrophotometric method. Small Km and large ko values were observed for the oxidized forms of FMA, FEA and TMPD compared to those for Co(Phen)3+(3) and Fe(CN)3-(6). It is suggested that the reaction pocket of the present diaphorase is hydrophobic. The present electrochemical procedure for the determination of the kinetic parameters is applicable widely to similar enzyme reactions. PMID- 2317517 TI - Purification and characterization of 3-ketosteroid-delta 1-dehydrogenase from Nocardia corallina. AB - The inducible 3-ketosteroid-delta 1-dehydrogenase of Nocardia corallina which catalyzes the introduction of a double bond into the position of carbon 1 and 2 of ring A of 3-ketosteroid has been obtained in four steps with a 50% yield and 360-fold purification. The enzyme is homogeneous as judged by SDS-gel electrophoresis and is a monomeric protein with a molecular weight of 60,500. The isoelectric point of the enzyme is about 3.1. The enzyme contains 1 mol of flavin adenine dinucleotide per mol of protein, and has a typical flavoprotein absorption spectrum with maxima of 458, 362 and 268 nm. The enzyme is very stable in the absence of added cofactors, and catalyzes the dehydrogenation of delta 4-3 ketosteroids in the presence of phenazine methosulfate, which acts as an excellent electron acceptor. Potassium ferricyanide and cytochrome c did not act as electron acceptors. The delta 1-dehydrogenation was also stimulated by molecular oxygen with stoichiometric production of hydrogen peroxide and delta 1,4-3-ketosteroid. The optimum pH is 10 for dehydrogenation using phenazine methosulfate, and is between 8.5 and 10 for the oxidase reaction. The enzyme oxidizes a wide variety of 3-ketosteroids, but not 3 beta-hydroxysteroids. 3 Ketosteroids having an 11 alpha- or 11 beta-hydroxyl group were oxidized at slow rates. The purified enzyme catalyzes efficiently aromatization of the A-ring of 19-nortestosterone and 19-norandrostenedione to produce estradiol and estrone. 19 Hydroxytestosterone, 19-hydroxyandrostenedion and 19-oxotestosterone were converted to the respective phenolic steroids with cleavage of the C10 side chain. Activities of 3-ketosteroid-delta 4-dehydrogenase, delta 5-3-ketosteroid 4,5-isomerase, 3 beta-hydroxysteroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase were not observed in the purified preparations. Properties of this novel flavoprotein enzyme are discussed. PMID- 2317518 TI - Immobilization of acetyl-CoA:arylamine N-acetyltransferase and the preparation of an enzyme reactor for the synthesis of N-[11C]acetylserotonin. AB - The enzyme arylamine acetyltransferase (acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) from pigeon liver is immobilized onto differently derivatized controlled pore glass beads. Different silanes, spacer arms and reactive end groups were tested, and immobilized enzyme stability tests were performed. From these experiments, the method of choice was selected: immobilization on controlled pore glass beads (24 nm pore size, 75-125 microns particle size) derivatized with gamma-aminopropyl and glutaraldehyde as the reactive end group. The kinetic properties of an enzyme reactor were investigated and optimized. The goal was to obtain a rapid high-yield conversion of 0.5-1 mumol acetyl-CoA to N acetylserotonin, so that the reactor is useful for the 11C-labelling of N acetylserotonin. Using an enzyme reactor (9.8 x 0.5 cm i.d.) containing 4.6 U active arylamine acetyltransferase immobilized onto 930 mg carrier, a 70% conversion of acetyl-CoA was obtained within 4 min. PMID- 2317519 TI - Inactivation of peroxidase by hydrogen peroxide and its protection by a reductant agent. AB - Hydrogen peroxide, the oxidant substrate of peroxidase, is also an inactivating agent of this enzyme. The reductant substrates protect the enzyme from the inactivating process. A reaction mechanism is proposed, in which two competitive routes exist for Compound I of peroxidase; one catalytic and one inactivating. The analytical solution produced at the end of the reaction supports the proposed mechanism and shows the dependence between the number of turnovers of the enzyme (r) and the ratio of both substrates. PMID- 2317520 TI - Spectral studies on the oxidation of organic sulfides (thioanisoles) by horseradish peroxidase compounds I and II. AB - Using both rapid-scan and conventional spectrophotometry, oxygenation of p substituted thioanisoles by horseradish peroxidase compounds I and II was investigated at pH 5, 7 and 9. The pH-jump technique was applied to the compound II reactions at acidic and neutral pH. The rate of oxidation of the sulfides is dependent on pH, concentration of substrate and on the different substituents in the para position of the benzene ring. Our results, based on transient state observations of the enzyme intermediates, are in agreement with the results of Kobayashi, S., Minoru, N., Kimura, T. and Schaap, A.P. (Biochemistry (1987) 26, 5019-5022), obtained using 18O-labelling and studies of product formation, in which formation of a sulfur cation radical from compound I is proposed. We consider two reaction mechanisms for the compound II reaction: one a one-electron oxidation of the thioanisole, analogous to the compound I reaction, and the other, the attack of the hydroxyl radical originating from compound II on the sulfur-cation radical. PMID- 2317521 TI - Abnormal cholesterol metabolism in imipramine-treated fibroblast cultures. Similarities with Niemann-Pick type C disease. AB - Addition of low-density lipoprotein (LDL) to cholesterol-deprived human skin fibroblast cultures treated by imipramine at a 20 microM concentration induced a significant intracellular accumulation of unesterified cholesterol. Intracytoplasmic inclusions were already visible by histochemical filipin staining after 2 h of LDL uptake and were progressively mobilized towards the perinuclear region within 24 h. At this concentration of the drug, the rate of proteolytic 125I-LDL hydrolysis was similar in treated and untreated cells. Treated cells maintained in lipoprotein-deficient medium showed no abnormality, indicating the exogenous origin of the accumulated sterol. Further, the drug induced a drastic dose-dependent impairment of LDL-stimulated cholesterol esterification, not related to an inhibition of acyl CoA:cholesterol acyltransferase, and a significant delay in down-regulation of de novo cholesterol synthesis. However, imipramine did not affect 25-hydroxycholesterol mediated regulation of the two latter processes. These results resemble those observed in Niemann-Pick type C disease and suggest an impaired mobilization of LDL-derived cholesterol in imipramine-treated cells. PMID- 2317522 TI - Changes in phospholipid composition and phospholipase D activity during the differentiation of Physarum polycephalum. AB - Changes in phospholipid composition and phospholipase D activity were observed during a differentiation from haploid myxoamoebae to diploid plasmodia of a true slime mold, Physarum polycephalum. In the amoeboid stage, the main components of phospholipid fraction were phosphatidylethanolamine (PE, 43.3%), phosphatidylcholine (PC, 28.8%) and phosphatidylinositol (PI, 8.0%), but in the plasmodial stage, PC was dominant (40.7%) and other main components were PE (31.5%) and phosphatidic acid (PA, 11.0%). The specific activity of phospholipase D in the plasmodia was 5.7-times higher than that in the myxoamoebae when measured in the presence of Ca2+ at the alkaline pH. In the amoeboid stage, phospholipase A activity (A1 or A2) was detected at the alkaline pH with Ca2+. Phospholipase D activity in the plasmodia was characterized: pH optimum was 6.0; Ca2+ was required for the reaction and Ba2+ could substitute partly for Ca2+; PE was the best substrate for the hydrolytic activity and PC and PI were not appreciably hydrolyzed; and all detergents tested inhibited the enzyme activity. PMID- 2317523 TI - Time-course of utilization of [stearic or lignoceric acid]sphingomyelin from high density lipoprotein by rat tissues. AB - Utilization of stearic and lignoceric acids supplied by high-density lipoprotein (HDL) sphingomyelin to different tissues was followed for 24 h after rats were injected with HDL containing [[1-14C]stearic (18:0) or [1-14C]lignoceric (24:0) acid [Me-3H]choline]sphingomyelin. Both isotopes reached a maximum in tissue lipids 3-12 h after injection and were recovered mainly in the liver (30%) and small intestine (3%), whereas the other tissues contained approx. 1% or less of the injected dose. All the tissues were able to take up some intact sphingomyelin from HDL and hydrolyze it. In the lung and erythrocytes, the 3H:14C ratio of sphingomyelin remained unchanged throughout the studied period, while an increase in the isotopic ratio was observed in the kidney due to the 3H choline moiety re used for synthesis of new sphingomyelin. Conversely, the isotopic ratio of sphingomyelin decreased in the liver, indicating a saving of the 14C-labelled fatty acids, especially 24:0. Furthermore, [24:0]ceramide in the liver remained at a high level (6% of the injected dose), whereas [18:0]ceramide decreased to 1%. When the tissues were examined 24 h after injection, the proportion of the 14C linked to sphingomyelin in the total 14C was always higher for both kinds of sphingomyelin than the molar proportion of sphingomyelin in the whole of lipid classes. However, in the majority of the extra-hepatic tissues, more [14C]18:0 than [14C]24:0 was recovered in sphingomyelin, and more 14C radioactivity from 18:0 than from 24:0 was redistributed in the other lipids. The choline moiety from both kinds of sphingomyelin was re-used to synthesize phosphatidylcholine, especially in the liver (up to 20% of the injected dose). All these results show that utilization of sphingomyelin from HDL by tissues normally occurs in vivo and that this phenomenon should be taken into account in the study of the phospholipid turnover of cell membranes. They also show that metabolism of sphingomyelin from HDL in the liver and other tissues is dependent on the sphingomyelin acyl moiety. PMID- 2317524 TI - Acylglycerol reactivity and reaction mechanism of bovine milk lipoprotein lipase. AB - The sequential lipolysis of trioleoylglycerol and the triacylglycerols of very low-density lipoprotein by bovine milk lipoprotein lipase can be described by the consecutive reactions: (formula: see text) where k'1, k'2 and k'3 are apparent first-order rate constants. The values of these rate constants dictate several conclusions concerning the reaction mechanism of this enzyme. The significant differences in the k'1, k'2 and k'3 values for trioleoylglycerol substrate imply that cleavage of the acyl-enzyme intermediate is not the rate-limiting step of the overall lipolysis reaction. This conclusion is further supported by the lack of an effect of hydroxylamine on the reaction rate. In addition, the observed isotope effect of k1 (H2O): k1(D2O) of 1.32 with trioleoylglycerol substrate suggests that the acyl-enzyme formation may contribute to the rate-limiting step of the lipoprotein-lipase-catalyzed reaction. In the presence of excess bovine serum albumin, the transfer of fatty acid product from the enzyme to albumin must be fast, since the k'1 values are not dependent on albumin concentration. When albumin is not in excess, the reaction is retarded and the study of reaction kinetics demonstrates negligible reaction after the available albumin is saturated. PMID- 2317525 TI - Effect of increasing amounts of dietary fish oil on brain and liver fatty composition. AB - Increasing dietary fish oil in rat had the following effect on brain lipids: Arachidonic acid regularly decreased; eicosapentanenoic acid, normally nearly undetectable, was present; 22:5(n - 3), dramatically increased but remained below 1% of total fatty acids; cervonic acid was increased by 30% at high fish oil concentration. Saturated and monounsaturated fatty acids were not affected regardless of chain-length. In contrast, in the liver, nearly all fatty acids (saturated, monounsaturated and polyunsaturated) were affected by high dietary content of fish oil, but liver function was normal: serum vitamin A and E, glutathione peroxidase, alkaline phosphatase, transaminases were not affected. Serum total cholesterol, unesterified cholesterol and phosphatidylcholine were slightly affected. In contrast, triacylglycerols were dramatically reduced in proportion to the fish oil content of the diet. PMID- 2317526 TI - Oxidation and reduction of bile acid precursors by rat hepatic 3 alpha hydroxysteroid dehydrogenase and inhibition by bile acids and indomethacin. AB - Enzyme kinetics of purified rat hepatic 3 alpha-hydroxysteroid dehydrogenase for bile acid precursors and effects of bile acids and indomethacin on those activities were studied. This enzyme catalyzed the oxidoreduction of the C3 position of bile acid precursors. Km for 7 alpha, 12 alpha-dihydroxy-5 beta cholestan-3-one (1.6 microM) was markedly lower than Km for 7 alpha-hydroxy-5 beta-cholestan-3-one (28 microM) but Vmax was similar. Km for 3 alpha, 7 alpha dihydroxy-5 beta-cholestane (12 microM) was lower than Km for 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestane (150 microM) although Vmax/Km values were similar for both compounds. Bile acids and indomethacin inhibited the reduction of 3-oxo bile acid precursors. NADPH inhibited the binding of lithocholic acid (3 alpha-hydroxy-5 beta-cholanic acid) by 3 alpha-hydroxysteroid dehydrogenase. These data suggest that intrahepatic bile acid concentrations may affect the reduction of 3-oxo-bile acid precursors and intrahepatic redox conditions may affect intracellular bile acid transfer. PMID- 2317527 TI - Interaction of lipoprotein lipase with glycosaminoglycans and apolipoprotein C II: effects of free-fatty-acids. AB - Lipoprotein lipase (LPL) bound to endothelial cells is released from the cell surface by triacylglycerol-rich lipoproteins and oleic acid (Saxena, U., Witte, L.D. and Goldberg, I.J. (1989) J. Biol. Chem. 264, 4349-4355). Studies were conducted to compare the ability of different fatty acids to release 125I labelled bovine milk LPL bound to endothelial cells and to define the mechanism for this effect. Using fatty acid/bovine serum albumin (BSA) solutions (molar ratio, 6:1), the release of LPL from endothelial cell surfaces using monounsaturated (18:1), polyunsaturated (18:2) and saturated (16:0) fatty acids was 78%, 60% and 28%, respectively. Release of LPL from heparin-agarose followed a similar pattern, suggesting that the fatty acids specifically affected LPL heparin interaction. Short-chain fatty acids (C6, C8 and C10), medium-chain fatty acids (C12 and C14) and elaidic acid, a transisomer of oleic acid, released less 125I-LPL than oleic acid from heparin-agarose. To determine whether oleic acid release of 125I-LPL from heparin-agarose was due to binding of the fatty acid to heparin or LPL, oleic acid was incubated with either LPL or heparin-agarose prior to performing the affinity chromatography. Only the prior incubation with LPL affected the binding to heparin-agarose. This demonstrates that dissociation of LPL from heparin required interaction of fatty acid with LPL. At high molar ratios of fatty acid:BSA (greater than 3:1), apo C-II is known to be ineffective as an activator of LPL. To determine whether this effect is due to decreased association of apo C-II with LPL, 125I-apo C-II (0.5-10 nmol) was allowed to bind to LPL-Sepharose. A 6:1 molar ratio of oleic acid:BSA produced up to 69% decrease in the amount of 125I-apo C-II bound to the gel. This dissociation of apo C-II from LPL by oleic acid was also demonstrated using gel-filtration chromatography. Thus, the amount and type of fatty acids may be important in regulating LPL activity in vivo by affecting both LPL interaction with glycosaminoglycans and with apo C-II. PMID- 2317528 TI - Omega- and (omega-1)-hydroxylation of arachidonic acid, lauric acid and prostaglandin A1 by multiple forms of cytochrome P-450 purified from rat hepatic microsomes. AB - The metabolism of arachidonic acid, lauric acid and prostaglandin A1 by rat hepatic microsomes and multiple forms of cytochrome P-450 purified from rat hepatic microsomes was studied. Arachidonic acid was hydroxylated by hepatic microsomes of male rats by omega- and (omega-1)-hydroxylation. Phenobarbital treatment of rats decreased the hydroxylation activity slightly, but 3 methylcholanthrene treatment increased the hydroxylation activity 2-fold. However, lauric acid and prostaglandin A1 omega- and omega-1)-hydroxylation activities decreased after treatment with phenobarbital and 3-methylcholanthrene. Arachidonic acid and lauric acid were metabolized with similar ratios of omega- and (omega-1)-hydroxylation, but prostaglandin A1 was efficiently metabolized at the omega-position by hepatic microsomes of untreated male rats. In a reconstituted system with purified cytochromes P-450, P450 UT-1, UT-2 (P-450h), MC-1 (P-450d) and MC-5 (P-450c) effectively hydroxylated arachidonic acid at both the omega- and (omega-1)-position. P450 UT-8 hydroxylated arachidonic acid only at the omega-position. P450 DM (P-450j) hydroxylated arachidonic acid at the (omega-1)-position efficiently. Lauric acid was also hydroxylated by P450 UT-1, UT-2, PB-1, PB-2, MC-1, IF-3 (P-450a) and DM, at the (omega - 1)-position only. Only P450 UT-8 could hydroxylate laruic acid at the omega-position. Prostaglandin A1 was efficiently and specifically metabolized by P450 UT-8 with omega hydroxylation. P450 UT-2 and PB-1 could hydroxylate prostaglandin A1 by (omega-1) hydroxylation, but with low activity. PMID- 2317529 TI - Identification of intermediates in the peroxisomal beta-oxidation of linoleic acid. AB - Rat liver peroxisomes contain a beta-oxidation system different from that present in the mitochondria. Intermediates in this oxidation have not hitherto been identified by direct methods. Incubation of linoleic acid with isolated peroxisomes (in the absence of detergent) resulted in the accumulation of polar products in addition to the chain-shortened products. Omission of NAD in the incubation mixture considerably increased the accumulation of these products. Two of the products were isolated and characterized by gas chromatography-mass spectrometry. They were identified as 2,3-dehydrolinoleic acid and 3 hydroxylinoleic acid, based on identical chromatographic behaviour and mass spectra compared to synthetic reference compounds. Stereochemical analysis of catalytically hydrogenated 3-hydroxylinoleic acid showed a D/L ratio near to one. The mechanism behind the apparent lack of stereospecificity is discussed in relation to the recently described novel peroxisomal 2-enoyl-CoA hydratase (Smeland, T.E., Li, J., Chu, C.-h., Cuebas, D. and Schultz, H. (1989) Biochem. Biophys. Res. Commun. 160, 988-992 and Hiltunen, J.K., Palosaari, P.M. and Kunau, W.-H. (1989) J. Biol. Chem. 264, 13536-13540). In previous work we have demonstrated that beta-oxidation intermediates accumulate also in the peroxisomal metabolism of C27-bile acid intermediates and prostaglandins. The possibility is discussed that the peroxisomal beta-oxidation system is less tightly coupled than the corresponding system in mitochondria. PMID- 2317531 TI - Biological rhythms in psychiatry: order and disorder. Society of Biological Psychiatry. Forty-fifth annual convention & scientific program. May 9-13, 1990, New York, New York. Program and abstracts. PMID- 2317530 TI - Cholesterol esters selectively taken up from high-density lipoproteins are hydrolyzed extralysosomally. AB - High-density lipoprotein (HDL) cholesterol esters (CE) are taken up by many cells without parallel uptake of HDL apoproteins. This selective uptake is mediated by reversible incorporation of HDL CE into a plasma membrane pool, from which the CE are internalized. We now show that selectively taken up CE are directed to an extralysosomal destination where they are hydrolyzed and available to the steroidogenic pathway. Cultured human fibroblasts take up HDL CE predominantly by selective uptake. Wolman's disease fibroblasts, which are deficient in lysosomal cholesterol esterase, effectively hydrolyzed CE from HDL, but not CE taken up in low density lipoproteins (LDL); normal fibroblasts hydrolyzed both effectively. Analogously, the lysosomotropic agent chloroquine effectively blocked hydrolysis of LDL CE but not HDL CE. A similar effect of chloroquine was seen in primary cultures of rat adrenal cells, which are very active in selective uptake. More than 50% of HDL CE taken up by adrenal cells appeared in the medium as corticosterone. To examine the subcellular destination of selectively taken up CE, non-hydrolyzable tracers of HDL and LDL CE were simultaneously injected into rats. On fractionation of adrenal glands 24 h after injection, 83% of the HDL CE tracer and 48% of the LDL CE tracer were recovered in cytoplasmic lipid droplets; that LDL tracer in the lipid droplets was accounted for by selective uptake of CE from LDL. Thus, selectively taken up cholesterol esters are processed by a mechanism distinct from the classical endosomal/lysosomal pathway, and are delivered to a cytoplasmic compartment. PMID- 2317532 TI - The biodegradability of polyester blends. AB - Blends of poly(epsilon-caprolactone) (PCL) and poly(L-lactic acid) (PLLA) with polyglycolic acid-co-L-lactic acid (PGLA) were prepared by three methods: compression moulding, coprecipitation, and solvent evaporation of a methylene chloride-in-water emulsion of the polymers. The rates of hydrolytic chain scission of each component of the blends were determined by deconvolution of GPC traces of samples maintained in phosphate buffer, pH 7.4, 37 degrees C, for up to 3000 h. The observed rates were dependent on the method of blending. For compression moulded blends, the rate of chain scission of PGLA was decreased and that of PCL and PLLA increased. A corresponding delay in the onset of weight loss was also observed. There was no evidence of blend miscibility. PMID- 2317533 TI - Clinical application of antithrombogenic hydrogel with long poly(ethylene oxide) chains. AB - Thirty clinical tests on PVC drain tubes coated with hydrophilic copolymer with long poly(ethylene oxide) chains (PEO-COAT) were carried out. Controls were non coated PVC drain tubes. Thrombogenesis was observed in 24 out of 30 non-coated PVC drain tubes (80%) and in only 4 out of 30 PEO-COAT drain tubes (13%). PEO COAT drain tubes significantly suppressed absorption of plasma proteins and adhesion of platelets. The excellent antithrombogenic property of this hydrophilic polymer, already suggested by in vitro and in vivo experiments, was demonstrated here clinically. PMID- 2317534 TI - Glycidyl methacrylate-styrene copolymer latex particles for immunologic agglutination tests. AB - New latex particles for immunologic agglutination reaction were prepared by a seeded polymerization technique for the emulsifier-free copolymerization of styrene and glycidyl methacrylate. The surface of the latex particles was presumed to be dotted with hydrophilic domains, giving stability to the particles. The remaining areas, to which many antigens or antibodies were strongly adsorbed, were hydrophobic. Various groups of the glycidyl methacrylate styrene latex particles were coated with human immunoglobulin G, and immunologic agglutinating potencies were compared by the box-titration method. Immunologic reactivities of the latex particles decreased with an increase of glycidyl methacrylate content at concentrations of 1 mol% or higher. Latex particles containing 0.5 to 0.75 mol% GMA caused strong immunologic agglutination besides showing good stability, indicating the availability of these latex particles. Glycidyl methacrylate-free polystyrene latex particles caused non-specific agglutination, while the immunologic agglutinating ability of glycidyl methacrylate-styrene latex particles, prepared by the unseeded polymerization technique was weak. PMID- 2317536 TI - Screening of in vitro cytotoxicity by the adhesive film test. AB - A novel procedure, the adhesive film test, is proposed as a screening method to predict potential cytotoxicity of biomaterials. This in vitro test utilizes a sterile strip of acrylate-based medical adhesive as an anchorage substrate in cytotoxicity studies. The adhesive film allows direct fixation of test samples to the base of the petri dish, ensuring close contact between sample and cells. The test is based on the principle that toxic components present in the test material will readily leach out into the culture medium and adversely affect the local cell population. The main advantage of the adhesive film test is that a viable cell population can be added directly to the test plate and after an incubation period of 24 h, the cellular response can be recorded as either cytotoxic or cytocompatible. Microscopic examination can be followed by quantifying the results using a micrometer to measure cellular attachment areas, migration distances and zones of inhibition. In addition, the adhesive film used to attach the test samples is shown to support extensive fibroblast growth and attachment to its surface and hence can also function as a negative nontoxic control in cytotoxicity studies. PMID- 2317535 TI - Adhesion and aggregation of thrombin prestimulated human platelets: evaluation of a series of biomaterials characterized by ESCA. AB - Five materials of interest in blood contact applications (PVC, Silastic, Biomer and siliconized glass) were internally coated on glass tubes and exposed to suspensions of platelets and red cells. Uncoated glass was also examined. Thrombin was added (prestimulation) to some suspensions before exposure to the biomaterial surfaces. The three polymeric surfaces were characterized by electron spectroscopy for chemical analysis (ESCA). Prestimulation with thrombin leads to increased adhesion of single platelets only with Silastic. With a wide range of surface types, thrombin prestimulation consistently leads to higher levels of platelet accumulation in the form of aggregates; the PVC-coated material showed the highest levels. ESCA analysis of PVC, however, suggested our coating was impure or an oxidized material. PMID- 2317537 TI - Workshop on the characterization of biomaterials in contact with blood. Siena, Italy, 18-19 January 1988. Abstracts. PMID- 2317538 TI - Measurement of the mechanical properties of the ovine anterior cruciate ligament bone-ligament-bone complex: a basis for prosthetic evaluation. AB - The reported ultimate tensile stress of the anterior cruciate ligament varies greatly, ranging from 13 to 147 MPa. This study shows that the orientation and degree of flexion of the bone-ligament-bone complex significantly alter the apparent ultimate tensile properties (ultimate tensile stress ranging from 60 +/- 3 to 123 +/- 15 MPa, ultimate specific extension from 37 +/- 7 to 93 +/- 20%), whilst the method chosen for measuring extension also affects the calculated specific extension of the bone-ligament-bone complex. It is suggested that, for considerations of prosthesis design and evaluation, the mechanical properties of the bone-ligament-bone complex should be measured in anterior draw and extension measured using points as close as possible to the positions of the ligamentous attachment sites. PMID- 2317539 TI - Intracerebral implantation of synthetic polymer/biopolymer matrix: a new perspective for brain repair. AB - Various poly (2-hydroxyethyl methacrylate)-collagen and poly (glyceryl methacrylate)-collagen composite hydrogels with varying porosities and cross linking densities were implanted into the cortex of adult rat brains to provide mechanical guiding substrates for wound healing and tissue ingrowth. The hydrogels were well tolerated by the neural tissue. After 2 and 3 month, hyper- and macroporous hydrogels (poly(glyceryl methacrylate)) with interconnected channel systems were penetrated by neural tissue and elements of extracellular matrices, with differences in the degree and the topographic patterning of tissue ingrowth according to the type of samples. These differences were ascribed to the geometry, size of the pore interconnections and the mechanical properties of the polymers. Hyper- and microporous hydrogels (poly(2-hydroxyethyl methacrylate)) and hydrogels without collagen were not penetrated by the host tissue. The compatibility of the polymers with the neural tissue was also tested in vitro. This study suggests a new approach to repair brain lesions consisting of loss of tissue volume. PMID- 2317540 TI - [Intra- and interindividual differences in tensile strength of human bone]. AB - In a biomechanical study we evaluated the stability of human femurs. In order to document the inter- and intraindividual differences in bending stability, we tested 200 bone samples, harvested from the femurs of 5 multiorgan donors. The bending tests were performed on a material testing machine (ZWICK) under standardized conditions. Our results revealed significant differences in the stability of the femurs of the 5 multiorgan donors. Furthermore, there was a significant difference in breaking strength at different levels of the same bone. CLINICAL RELEVANCE: In studies aimed at evaluating the primary bony stability of alloimplants after different preservation or sterilization procedures, the above mentioned results should be taken into consideration. PMID- 2317541 TI - [The cementless artificial hip cup--implant components with reliable long-term stability?]. AB - A hip joint simulator was developed to analyse the mechanism of loosening of cementless artificial hip cups. The machine induces vibrating motions and asymmetrical tilt shock loadings of the artificial cup. On measuring the primary stability of threaded cups, the simulation tests performed on pelvis substitute models, and animal and human acetabula failed to show any loosening of threaded cups fixed in place with a screw-in torque of more than 10 Nm. Instable cups became loose all the sooner, the lower the preload between the cup and femoral head. This demonstrates the importance of both the screw-in torque of the cup and the training status of the periarticular muscles. PMID- 2317542 TI - ["Glucosensor Unitec Ulm". A portable, continuously measuring glucose sensor and monitor]. AB - The "Glucosensor Unitec Ulm" is the first commercially available, portable glucose monitor that permits continuous measurement in venous blood under ambulatory conditions for up to 256 hours. The device weights 850 g, and measures 15 x 19 x 7 cm. Depending on the flow rate of the pump, the blood requirement is 15-25 ml/24 h. The size of the built-in-memory is 32 kByte, enough to store 3180 15,900 glucose values. The "24 hour glucogram" obtained under day to day living conditions permits the detection of disturbances of carbohydrate metabolism. Thus, early abnormalities of type II diabetes can be detected as well the degree of blood glucose normalization in patients suffering from severe insulin dependent diabetes. Moreover, the effects of glucose-lowering drugs can be analyzed objectively. Finally, this portable glucose monitor permits the recognition of hypoglycemia induced by insulin administration or endogenous insulin overproduction due to tumors. PMID- 2317543 TI - [A sterile, regulated, pulsation-dampened precision dosing system for biomedical technics]. AB - For sterile continuous metering of small and very small flow rates delivered by peristaltic pump, a gravimetric control system which permits a high accuracy of mass flow is described. This is achieved by a digital PI controller and a digital filter with which the very accurate signal from a high precision electronic scale is filtered. In addition proposals are made for solving the problem of refilling the reservoir and for compensating the pulsations caused by the peristaltic pump. PMID- 2317544 TI - Dielectrophoretic spectra of single cells determined by feedback-controlled levitation. AB - In this paper we have utilized the principle of dielectrophoresis (DEP) to develop an apparatus to stably levitate single biological cells using a digital feedback control scheme. Using this apparatus, the positive DEP spectra of both Canola plant protoplast and ligament fibroblast cells have been measured over a wide range of frequencies (1 kHz to 50 MHz) and suspending medium conductivities (11-800 muS/cm). The experimental data thus obtained have been interpreted in terms of a simple spherical cell model. Furthermore, utilizing such a model, we have shown that various cellular parameters of interest can be readily obtained from the measured DEP levitation spectrum. Specifically, the effective membrane capacitance of single cells has been determined. Values of 0.47 +/- 0.03 muF/cm2 for Canola protoplasts and 1.52 +/- 0.26 muF/cm2 for ligament fibroblasts thus obtained are consistent with those determined by other existing electrical methods. PMID- 2317545 TI - Inhomogeneous broadening in spectral bands of carbonmonoxymyoglobin. The connection between spectral and functional heterogeneity. AB - The rebinding kinetics of CO to myoglobin after flash photolysis is nonexponential in time below approximately 180 K; the kinetics is governed by a distribution of enthalpic barriers. This distribution results from inhomogeneities in the protein conformation, referred to as conformational substates. Hole-burning experiments on the Soret and IR CO-stretch bands test the assumption that an inhomogeneous distribution of conformational substates results in inhomogeneously broadened spectra. CO was slowly photolyzed at different wavelengths in the Soret band at 10 K. Both the Soret band and the CO-stretch band A1, centered at 1,945 cm-1, shift during photolysis, demonstrating that different wavelengths excite different parts of the distributed population. We have also done kinetic hole-burning experiments by measuring peak shifts in the Soret and A1 bands as the CO molecules rebind. The shifts indicate that the spectral and enthalpic distributions are correlated. In the A1 band, the spectral and enthalpic distributions are highly correlated while in the Soret the correlation is weak. From the peak shifts in the spectral and kinetic hole burning experiments the inhomogeneous broadening is estimated to be approximately 15% of the total width in the Soret band and approximately 60% in A1. We have previously measured the tilt angle alpha between the bound CO and the heme normal (Ormos, P., D. Braunstein, H. Frauenfelder, M. K. Hong, S.-L. Lin, T. B. Sauke, and R. D. Young. 1988. Proc. Natl. Acad. Sci. USA. 85:8492-8496) and observed a wave number dependence of the tilt angles within the CO-stretch A bands. Thus the spectral and enthalpic distributions of the A bands are coupled to a heterogeneity of the structure. PMID- 2317546 TI - Cross-bridge cycling theories cannot explain high-speed lengthening behavior in frog muscle. AB - The Huxley 1957 model of cross-bridge cycling accounts for the shortening force velocity curve of striated muscle with great precision. For forced lengthening, however, the model diverges from experimental results. This paper examines whether it is possible to bring the model into better agreement with experiments, and if so what must be assumed about the mechanical capabilities of cross bridges. Of particular interest is how introduction of a maximum allowable cross bridge strain, as has been suggested by some experiments, affects the predictions of the model. Because some differences in the models are apparent only at high stretch velocities, we acquired new force-velocity data to permit a comparison with experiment. Using whole, isolated frog sartorius muscles at 2 degrees C, we stretched active muscle at speeds up to and exceeding 2 Vmax. Force during stretch was always greater than the peak isometric level, even during the fastest stretches, and was approximately independent of velocity for stretches faster than 0.5 Vmax. Although certain modifications to the model brought it into closer correspondence with the experiments, the accompanying requirements on cross bridge extensibility were unreasonable. We suggest (both in this paper and the one that follows) that sarcomere inhomogeneities, which have been implicated in such phenomena as "tension creep" and "permanent extra tension," may also play an important role in determining the basic force-velocity characteristics of muscle. PMID- 2317547 TI - New insights into the behavior of muscle during active lengthening. AB - A muscle fiber was modeled as a series-connected string of sarcomeres, using an A. V. Hill type model for each sarcomere and allowing for some random variation in the properties of the sarcomeres. Applying stretches to this model led to the prediction that lengthening of active muscle on or beyond the plateau of the length tension curve will take place very nonuniformly, essentially by rapid, uncontrolled elongation of individual sarcomeres, one at a time, in order from the weakest toward the strongest. Such a "popped" sarcomere, at least in a single fiber, will be stretched to a length where there is no overlap between thick and thin filaments, and the tension is borne by passive components. This prediction allows modeling of many results that have previously been inexplicable, notably the permanent extra tension after stretch on the descending limb of the length tension curve, and the continued rise of tension during a continued stretch. PMID- 2317548 TI - Mapping of fluorescence anisotropy in living cells by ratio imaging. Application to cytoplasmic viscosity. AB - Steady-state and time-resolved fluorescence properties of probes incorporated into living cells give information about the microenvironment near the probe. We have extended studies of spatially averaged fluorescence anisotropy (r) by using an epifluorescence microscope, equipped with excitation and emission polarizers and an image analysis system, to map r of nonoriented fluorophores incorporated into cultured cells. With this imaging system, r for reflected light or glycogen scattering solutions was greater than 0.98. Measurement of r over the range 0.01 0.35 for fluorophores in bulk solution and in thin capillary tubes placed side-by side gave values equivalent to r measured by cuvette fluorometry. Cytoplasmic viscosity (eta) in Madin-Darby canine kidney (MDCK) cells and Swiss 3T3 fibroblasts was examined from anisotropy images and time-resolved fluorescence decay of the cytoplasmic probes 2,7-bis-carboxyethyl-5 (and 6)-carboxy fluorescein (BCECF) and indo-1. Nanosecond lifetimes and anisotropy decay were measured using a pulsed light source and gated detector interfaced to the epifluorescence microscope. Anisotropy images of BCECF in MDCK cells revealed two distinct regions of r: one from the cytoplasm (r = 0.144 +/- 0.008) and a second appearing at late times from the interstitial region (r = 0.08 +/- 0.03), representing BCECF trapped beneath the tight junctions. Anisotropy values, taken together with intracellular life-times and the calibration between r and eta/tau f for water/glycerol mixtures, gave eta values of 10-13 cP at 23 degrees C. These values assume little fluorophore binding to intracellular components and are therefore upper limits to cytoplasmic viscosity. These data establish a new methodology to map anisotropy in intact cells to examine the role of fluidity in cellular physiology. PMID- 2317549 TI - Cell membrane fluidity in the intact kidney proximal tubule measured by orientation-independent fluorescence anisotropy imaging. AB - Membrane fluidity was measured in the isolated perfused proximal tubule from rabbit kidney. The apical and basolateral plasma membranes of tubule cells were stained separately with the fluidity-sensitive fluorophore trimethylammonium diphenyl-hexatriene (TMA-DPH) by luminal or bath perfusion. Fluorescence anisotropy (r) of TMA-DPH was mapped with spatial resolution using an epifluorescence microscope (excitation 380 nm, emission greater than 410 nm) equipped with rotatable polarizers and a quantitative imaging system. To measure r without the confounding effects of fluorophore orientation, images were recorded with emission polarizer parallel and perpendicular to a continuum of orientations of the excitation polarizer. The theoretical basis of this approach was developed and its limitations were evaluated by mathematical modeling. The tubule inner surface (brush border) was brightly stained when the lumen was perfused with 1 microM TMA-DPH for 5 min; apical membrane r was 0.281 +/- 0.006 (23 degrees C). Staining of the tubule basolateral membrane by addition of TMA DPH to the bath gave a significantly lower r of 0.242 +/- 0.010 (P less than 0.005); there was no staining of the brush border membrane. To interpret anisotropy images quantitatively, effects of tubule geometry, TMA-DPH lifetime, fluorescence anisotropy decay, and objective-depolarization were evaluated. Steady-state and time-resolved r and lifetimes in the intact tubule, measured by a nanosecond pulsed microscopy method, were compared with results in isolated apical and basolateral membrane vesicles from rabbit proximal tubule measured by cuvette fluorometry; r was 0.281 (apical membrane) and 0.276 (basolateral membrane) (23 degrees C). These results establish a methodology to quantitate membrane fluidity in the intact proximal tubule, and demonstrate a significantly higher fluidity in the basolateral membrane than in the apical membrane. PMID- 2317550 TI - Lateral diffusivity of lipid analogue excimeric probes in dimyristoylphosphatidylcholine bilayers. AB - The lateral mobility of pyrenyl phospholipid probes in dimyristoylphosphatidylcholine (DMPC) vesicles was determined from the dependence of the pyrene monomeric and excimeric fluorescence yields on the molar probe ratio. The analysis of the experimental data makes use of the milling crowd model for two-dimensional diffusivity and the computer simulated random walks of probes in an array of lipids. The fluorescence yields for 1-palmitoyl-2-(1' pyrenedecanoyl)phosphatidylcholine (py10PC) in DMPC bilayers are well fitted by the model both below and above the fluid-gel phase transition temperature (Tc) and permit the evaluation of the probe diffusion rate (f), which is the frequency with which probes take random steps of length L, the host membrane lipid-lipid spacing. The lateral diffusion coefficient is then obtained from the relationship D = fL2/4. In passing through the fluid-gel phase transition of DMPC (Tc = 24 degrees C), the lateral mobility of py10PC determined in this way decrease only moderately, while D measured by fluorescence photobleaching recovery (FPR) experiments is lowered by two or more orders of magnitude in gel phase. This difference in gel phase diffusivities is discussed and considered to be related either to (a) the diffusion length in FPR experiments being about a micrometer or over 100 times greater than that of excimeric probes (approximately 1 nm), or (b) to nonrandomicity in the distribution of the pyrenyl probes in gel phase DMPC. At 35 degrees C, in fluid DMPC vesicles, the diffusion rate is f = 1.8 x 10(8) s-1, corresponding to D = 29 microns2 s-1, which is about three times larger than the value obtained in FPR experiments. The activation energy for lateral diffusion in fluid DMPC was determined to be 8.0 kcal/mol. PMID- 2317551 TI - Dipyrenylphosphatidylcholines as membrane fluidity probes. Relationship between intramolecular and intermolecular excimer formation rates. AB - In the intramolecular excimeric membrane probe, dipyrenylphosphatidylcholine (dipyn PC), pyrene moieties are linked to the terminal carbons of the two acyl chains, each of which contains n carbons. We show here how the probe intramolecular excimer production rate, K, may be determined from the excimer/monomer intensity ratio, rl, by making use of the fluorescence titrations of the related monopyrenyl probe, pyn PC, analyzed according to the milling crowd model. rl and the rate K of dipy10 PC in four model membrane systems were measured over a wide temperature range and both parameters are shown to be sensitive functions of the lateral fluidity of the host matrix. A model for relating the intramolecular and intermolecular excimer formation rates is proposed according to which both processes are limited by the reorientational rate of the pyrene moiety. Above the fluid-gel transition temperature, Tc, the diffusion rate (f) of the monopyrenyl probe (pyn PC) is accordingly related to K by: pE approximately K/(K + 1/2f + tau -1M), where pE is the probability of excimer formation between nearest neighbor pyn PC probes, and tau M is the monomer lifetime. Values of pE derived in this way are found to be consistent with pE values derived from the milling crowd analysis of fluorescence yield titration experiments. K for dipy10 PC in DMPC multibilayers ranges from 0.21 x 10(7) s-1 at 10 degrees C in the gel phase, to 5.7 x 10(7) s-1 at 60 degrees C in the fluid phase, whereas the lateral diffusion coefficient, D, for py10 PC in the same bilayers ranged from 8 to 34 microns2 s-1, when calculated with D = fL2/4, L being the average lipid-lipid spacing of the host membrane. Above Tc and at the same reduced temperature, (T - Tc)/Tc, both f for py10 PC, and K for dipy10 PC were found to have relative magnitudes in the order: DPPC greater than DMPC greater than POPC greater than DOPC. This and the similarity of the activation energies for f and K suggest that the rotation of the the pyrene moiety is the rate-limiting step for both the lateral mobility of py10 PC and intramolecular excimer formation in dipy10 PC. PMID- 2317552 TI - High sensitivity electron diffraction analysis. A study of divalent cation binding to purple membrane. AB - A sensitive high-resolution electron diffraction assay for change in structure is described and harnessed to analyze the binding of divalent cations to the purple membrane (PM) of Halobacterium halobium. Low-dose electron diffraction patterns are subject to a matched filter algorithm (Spencer, S. A., and A. A. Kossiakoff. 1980. J. Appl. Crystallogr. 13:563-571). to extract accurate values of reflection intensities. This, coupled with a scheme to account for twinning and specimen tilt in the microscope, yields results that are sensitive enough to rapidly quantitate any structure change in PM brought about by site-directed mutagenesis to the level of less than two carbon atoms. Removal of tightly bound divalent cations (mainly Ca2+ and Mg2+) from PM causes a color change to blue and is accompanied by a severely altered photocycle of the protein bacteriohodopsin (bR), a light-driven proton pump. We characterize the structural changes that occur upon association of 3:1 divalent cation to PM, versus membranes rendered purple by addition of excess Na+. High resolution, low dose electron diffraction data obtained from glucose-embedded samples of Pb2+ and Na+ reconstituted PM preparations at room temperature identify several sites with total occupancy of 2.01 +/- 0.05 Pb2+ equivalents. The color transition as a function of ion concentration for Ca2+ or Mg2+ and Pb2+ are strictly comparable. A (Pb2(+)-Na+) PM Fourier difference map in projection was synthesized at 5 A using the averaged data from several nominally untilted patches corrected for twinning and specimen tilt. We find six major sites located on helices 7, 5, 4, 3, 2 (nomenclature of Engelman et al. 1980. Proc. Natl. Acad. Sci. USA. 77:2023-2027) in close association with bR. These partially occupied sites (0.55-0.24 Pb2+ equivalents) represent preferential sites of binding for divalent cations and complements our earlier result by x-ray diffraction (Katre et al. 1986. Biophys. J. 50:277-284). PMID- 2317553 TI - Calcium diffusion modeling in a spherical neuron. Relevance of buffering properties. AB - We have developed a calcium diffusion model for a spherical neuron which incorporates calcium influx and extrusion through the plasma membrane as well as three calcium buffer systems with different capacities, mobilities, and kinetics. The model allows us to calculate the concentration of any of the species involved at all locations in the cell and can be used to account for experimental data obtained with high-speed Ca imaging techniques. The influence of several factors on the Ca2+ transients is studied. The relationship between peak [Ca2+]i and calcium load is shown to be nonlinear and to depend on buffer characteristics. The time course of the Ca2+ signals is also shown to be dependent on buffer properties. In particular, buffer mobility strongly determines the size and time course of Ca2+ signals in the cell interior. The model predicts that the presence of exogenous buffer, such as fura-2, modifies the Ca2+ transients to a variable extent depending on its proportion relative to the natural, intrinsic buffers. The conclusions about natural calcium buffer properties that can be derived from Ca imaging experiments are discussed. PMID- 2317554 TI - Determination of three-dimensional imaging properties of a light microscope system. Partial confocal behavior in epifluorescence microscopy. AB - We have determined the three-dimensional image-forming properties of an epifluorescence microscope for use in obtaining very high resolution three dimensional images of biological structures by image processing methods. Three dimensional microscopic data is collected as a series of two-dimensional images recorded at different focal planes. Each of these images contains not only in focus information from the region around the focal plane, but also out-of-focus contributions from the remainder of the specimen. Once the imaging properties of the microscope system are characterized, powerful image processing methods can be utilized to remove the out-of-focus information and to correct for image distortions. Although theoretical calculations for the behavior of an aberration free microscope system are available, the properties of real lenses under the conditions used for biological observation are often far from an ideal. For this reason, we have directly determined the image-forming properties of an epifluorescence microscope under conditions relevant to biological observations. Through-focus series of a point object (fluorescently-coated microspheres) were recorded on a charge-coupled device image detector. From these images, the three dimensional point spread function and its Fourier transform, the optical transfer function, were derived. There were significant differences between the experimental results and the theoretical models which have important implications for image processing. The discrepancies can be explained by imperfections of the microscope system, nonideal observation conditions, and partial confocal effects found to occur with epifluorescence illumination. Understanding the optical behavior of the microscope system has indicated how to optimize specimen preparation, data collection, and processing protocols to obtain significantly improved images. PMID- 2317555 TI - Ligand dynamics in the photodissociation of carboxyhemoglobin by subpicosecond transient infrared spectroscopy. AB - Time-resolved infrared spectroscopy with 0.5-ps resolution is used to track the evolution of the CO stretching vibration after visible photoexcitation of carboxyhemoglobin in water at room temperature. Polarization measurements determine that the iron-complexed CO is oriented nearly perpendicular to the porphyrin plane. The dissociation appears to proceed via a metastable excited state with 2 +/- 1 ps lifetime. The dissociated CO binds weakly in the heme pocket for at least 500 ps. This state correlates with the internally bound state observed by Frauenfelder et al. at low temperatures in myoglobin. PMID- 2317556 TI - On the analysis of high order moments of fluorescence fluctuations. AB - A simple, straightforward analysis to characterize the distribution of aggregate sizes in a reversible aggregation system at equilibrium is presented. The method, an extension of fluorescence correlation spectroscopy (FCS), is based on measurements of higher order moments of spontaneous fluctuations of fluorescence intensity emitted from a defined open region of the sample. These fluctuations indicate fluctuations of the numbers of the fluorescent molecules in the observation region. Shot noise resulting from the random character of fluorescence emission and from the photoelectric detection system is modeled as a Poisson distribution and is subtracted from the measured photon count fluctuation moments to yield the desired fluorescence fluctuation moments. This analysis can also be used to estimate the fraction of immobile fluorophores in FCS measurements. PMID- 2317557 TI - Evidence that several high-frequency human blood group antigens reside on phosphatidylinositol-linked erythrocyte membrane proteins. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder associated with absence of expression of phosphatidylinositol (PI)-linked membrane proteins from circulating hematopoietic cells of multiple lineages. Recent work demonstrated that decay accelerating factor, one such PI-linked protein, bears the Cromer related blood group antigens. This study demonstrated that other high incidence antigens, including Cartwright (Yta/Ytb), Holley-Gregory (Hy/Gya), John Milton Hagen (JMH), and Dombrock (Doa/Dob), are absent from the complement-sensitive (PNH III) erythrocytes of patients with PNH. The relatively normal, complement insensitive erythrocytes from the same patients express these antigens normally. Therefore, these antigens most likely reside on PI-linked proteins absent from PNH III, but not PNH I, erythrocytes. PMID- 2317558 TI - Molecular studies of von Willebrand disease: reduced von Willebrand factor biosynthesis, storage, and release in endothelial cells derived from patients with type I von Willebrand disease. AB - Endothelial cells were cultured from the umbilical veins of two neonates with type I von Willebrand disease (vWD) and compared with cells cultured in parallel from normal control umbilical veins. In both cases, cultured vWD endothelial cells contained less messenger RNA (mRNA) encoding von Willebrand factor (vWF), and constitutively secreted two- to fourfold less vWF protein than their matched controls. Regulated secretion of stored vWF induced by thrombin or phorbol-12 myristate-13-acetate (PMA) was also diminished in vWD cells. Both the mRNA and protein produced by each of these type I vWD cells appeared to be of normal size. However, despite the diminished size of the vWF storage pool, electron microscopy of endothelial cells in situ showed normal appearing vWF storage organelles (Weibel-Palade bodies). These studies show that cultured umbilical vein endothelial cells can be used to explore the molecular defects in type I and perhaps other forms of vWD, and suggest that at least some forms of type I vWD are caused by diminished mRNA transcription or subsequent translation due to a defective vWF allele. PMID- 2317559 TI - Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity. AB - Rabbits were given polyclonal anti-tissue factor (TF) immunoglobulin G (IgG) before an injection of endotoxin to test the hypothesis that TF triggers disseminated intravascular coagulation (DIC) after endotoxin. The rabbits had been prepared with cortisone to develop DIC after one injection of endotoxin. Anti-TF IgG substantially reduced the falls in fibrinogen, factors V and VIII, and platelets noted in control rabbits given preimmune IgG before endotoxin. At autopsy 24 hours later, fibrin was present in glomerular capillaries of 4 of 5 control rabbits, but in none of 11 rabbits given anti-TF IgG. DIC was also induced in a second group of rabbits by the infusion, over 4 hours, of 1 microgram/kg of purified, reconstituted rabbit brain TF. This resulted in striking falls in plasma fibrinogen, factors V, and VIII that were diminished, but not prevented by prior treatment with anti-TF IgG. Circulating activated factor VII, induced by either TF infusion or endotoxin, could not be detected after DIC. Mean plasma extrinsic pathway inhibitor (EPI) activity did not fall significantly after endotoxin, and only to about 65% of the preinfusion after infusion of TF. Thus, DIC induced by both agents proceeded despite nearly normal plasma EPI levels. Because EPI neutralizes factor VIIa/TF in vitro only after a short lag period, the DIC that persisted for up to 6 hours after injection of endotoxin suggests that TF activity continued to be generated during this period on cells to which the circulating blood was exposed. All animals given endotoxin became ill with cyanosis, tachypnea, cold ears, and diarrhea, regardless of whether they had received anti-TF IgG to attenuate DIC. Infusion of TF caused some animals to die acutely with pulmonary arterial thromboses, but surviving animals did not appear ill. The findings support the hypothesis that exposure of blood to TF triggers DIC after endotoxin, but is not important for the pathogenesis of endotoxin-induced shock. PMID- 2317560 TI - Mechanisms accounting for the defective natural killer activity in patients with hairy cell leukemia. AB - Natural killer (NK) cell activity is severely impaired in untreated patients with hairy cell leukemia (HCL). In an attempt to investigate whether this impairment is related to a defect at the target cell binding and/or at the post target cell binding level, we evaluated the peripheral blood mononuclear cells (PBMC) of HCL patients for their ability to: (1) bind and kill K-562 NK-sensitive targets at the single cell binding level; (2) release the NK cytotoxic factor (NKCF) under different in vitro stimuli, including K-562 and phytohemoagglutinin; and (3) kill K-562 targets in a lectin-dependent cellular cytoxicity (LDCC) assay. This study demonstrates that untreated HCL patients' PBMC show a low ability to form conjugates with K-562 targets at the single cell binding level (5.7% +/- 1.0%) with respect to patients studied after treatment (9.3% +/- 1.3%) and controls (15.0% +/- 4.0%); P less than .05 and P less than .001, respectively. A decreased ability to kill the bound target was demonstrated in untreated cases (1.2% +/- 1.1%) versus patients studied after treatment and controls (12.3% +/- 1.6%, 17.0% +/- 3.1% respectively); P less than .001 in both conditions. After activation of effector cells with interleukin-2 (IL-2) in vitro, an increase in the ability of PBMC to form conjugates with K-562 targets and kill the bound target was demonstrated in each group of patients. Moreover, IL-2 was able to increase the cytotoxicity against NK-sensitive targets in all patients tested. Evaluation of NKCF production showed that untreated patients release low levels of NKCF when PBMC were incubated in the presence of K-562 stimulators (1.8% +/- 0.7%) with respect to patients after interferon-alpha (IFN-alpha) therapy (7.6% +/- 2.1%) and controls (12.9% +/- 2.2%); P less than .02 and P less than .001, respectively. When the recognition mechanisms were bypassed by triggering the cells with lectins in an LDCC assay, we demonstrated an increase of the lytic activity in both groups of patients with respect to the baseline values. However, the cytotoxic capacity observed in untreated patients was significantly lower than that observed in subjects after IFN-alpha therapy and controls (P less than .001). These findings suggest that the impaired NK activity observed in patients with HCL is related to defects both at the target and posttarget cell binding levels. PMID- 2317561 TI - The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis. AB - Acute myelofibrosis is often associated with acute megakaryoblastic leukemia (AMKBL). Although the exact mechanism for the progression of myelofibrosis in AMKBL is unclear, certain humoral factors from megakaryoblastic cells, the precursors of platelets, may be involved in the enhancement of collagen synthesis by bone marrow fibroblasts. The present study, therefore, is an investigation of the possible pathogenic role of transforming growth factor-beta (TGF-beta), known to be a very potent collagen-stimulating factor found in platelets in the myelofibrosis of AMKBL. The results obtained were as follows: (1) Conditioned media from peripheral megakaryoblasts taken from an AMKBL patient and from established megakaryoblast cell lines (MEG-01) had much greater stimulatory effects on collagen synthesis in bone marrow fibroblasts than conditioned media from other leukemic cell types. (2) Based on an assessment of soft agar colony formation, there was greater TGF-beta activity in media that had been conditioned from megakaryoblasts than in media from other leukemic cell types. (3) When compared with other leukemic-cell types, megakaryoblasts showed substantially greater expression of TGF-beta mRNA that was hybridized at 2.5 kb with a TGF-beta cDNA probe, and TGF-beta polypeptides were detected at 13 Kd with anti-TGF-beta antibodies. (4) The addition of the anti-TGF-beta antibody inhibited the stimulatory effects of the megakaryoblast conditioned medium on collagen synthesis in bone marrow fibroblasts. These results clearly suggest that megakaryoblasts produce and secrete an active form of TGF-beta and stimulate collagen synthesis in bone marrow fibroblasts in a paracrine manner. PMID- 2317562 TI - Shed tumor gangliosides and progression of human neuroblastoma. AB - Shedding of membrane gangliosides is characteristic of human and experimental tumors. Because some shed tumor gangliosides have potent tumor-enhancing properties, significant ganglioside shedding could influence tumor progression. We examined this possibility in a human tumor, neuroblastoma. Ganglioside shedding, measured as circulating tumor-derived GD2 ganglioside, and the outcome of 74 patients with advanced stage (III and IV) disease were studied. Progression free survival (PFS) was inversely related to circulating GD2 levels at the time of diagnosis (P = .018). By Kaplan-Meier analysis, the quartile of patients having the highest circulating GD2 levels (greater than or equal to 568 pmol/mL) had a strikingly different outcome from the quartile of patients with the lowest (less than or equal to 103 pmol/mL) GD2 levels (P = .013): median PFS was shorter (9 v 28 months), and the long-term survival rate lower (2-year PFS of 24% v 70%). We conclude that more rapid disease progression and lower survival rate are associated with high circulating GD2 levels at diagnosis and speculate that shed neuroblastoma tumor gangliosides play a role in accelerating tumor progression. PMID- 2317563 TI - Artificial surface effect on red blood cells and platelets in laminar shear flow. AB - Red blood cell (RBC) effects on platelet adhesion to a nonbiologic test surface (tetrafluoroethylene propylene copolymer) and platelet aggregation during laminar shear flow for shear rates to 5,680 s-1 (corresponding to shear stress to 200 dyne/cm2) were investigated. Results on hemoglobin (Hb) and adenosine diphosphate (ADP) release from RBCs, percent decrease of single platelets in the bulk, and percent of test surface covered with platelets were obtained in a cone-and-plate (CP) viscometer for samples of whole blood, suspensions of RBC ghosts in platelet rich plasma (PRP), and suspensions of RBCs in either PRP or platelet-poor plasma. Results obtained over the shear rate range studied for samples of normal hematocrit indicated that low-stress shearing led to ADP and Hb release from intact RBCs; shear-induced release of ADP from RBCs was about twice that of platelets, and of the total ADP released, the ADP released from RBCs contributed about six times that of the platelets to single platelet reduction in the bulk and about twice that of the platelets to platelet adhesion, ie, coverage of the test surface with platelets. Results obtained for various hematocrits showed that above a threshold hematocrit of about 25% to 35% the RBCs (suspended in PRP) had a greater contribution to ADP release, platelet adhesion, and platelet aggregation than the platelets themselves. Single platelet reduction for samples of RBC ghosts suspended in PRP correlated with shear rate level and not with shear stress. PMID- 2317564 TI - Immunoglobulin G subclass deficiency and pneumococcal infection after allogeneic bone marrow transplantation. AB - Serum immunoglobulin (Ig) G subclass levels were measured in a radial immunodiffusion assay in 25 leukemic patients before and after allogenic bone marrow transplantation. All patients received a conditioning regimen of busulfan and cyclophosphamide followed by infusion of marrow from an HLA-identical sibling. Intravenous infusions of a commercial Ig preparation were administered every 2 weeks until day 120 posttransplant. Nine patients developed pneumococcal infections at 6 months or greater posttransplant. Infection was associated with low levels or the absence of detectable serum IgG2 and IgG4. At the time of infection, 4 of 7 patients evaluated had undetectable IgG2, while 5 of 7 had undetectable levels of IgG4. After infection, none of the 8 patients evaluated had detectable levels of IgG2, and only 2 of 8 had detectable levels of IgG4. In contrast, all 16 patients without pneumococcal infection had IgG2 levels of 102 mg/dL or greater, and IgG4 levels of 20 mg/dL or greater. It appears that IgG2 and IgG4 subclass deficiencies after allogenic bone marrow transplantation contribute to susceptibility to pneumococcal infection. After pneumococcal infection, IgG2 and IgG4 levels remain low for a prolonged period and patients remain susceptible to infection by encapsulated organisms. PMID- 2317565 TI - Gene transfer into hematopoietic cells. PMID- 2317567 TI - Auto-antigens in Wegener's granulomatosis. PMID- 2317566 TI - Genetic mechanisms in chronic myelogenous leukemia. PMID- 2317568 TI - Phase II cooperative study with a new alkylating drug, PTT-119, in the treatment of non-Hodgkin's lymphomas. AB - In a phase II cooperative study involving eleven Italian haematological units, the efficacy and toxicity of a new alkylating compound, PTT-119, was evaluated in 53 patients with non-Hodgkin's lymphoma (NHL). Forty-five of the patients had been previously treated with various regimens of chemotherapy, the remaining eight were at the onset of the disease. PTT-119 was scheduled at 3.0 mg/kg every three weeks for a minimum of three administrations. Seven patients achieved a complete remission (CR), 19 a partial remission (PR); the overall response rate was 49%. The median duration of response was 6 months. Most frequent adverse effects were alopecia, nausea and vomiting and phlebitis due to the drug infusion. Myelosuppression was severe only in patients with bone marrow involvement or who were heavily pretreated. No liver, cardiac or renal toxicity was recorded. These data indicate that PTT-119 is an effective drug in the treatment of NHL; the matter of its non-cross-resistance with other alkylating compounds warrants further studies. PMID- 2317569 TI - IgG replacement therapy for primary hypogammaglobulinaemia during pregnancy: report of 9 pregnancies in 4 patients. AB - We report the cases of four pregnant women with primary hypogammaglobulinaemia, who received intramuscular, intravenous or no replacement therapy with IgG in late pregnancy, and review the literature. Intravenous replacement administered to the mother during pregnancy produces adequate serum IgG levels in the neonate, and should be the treatment of choice in this situation. PMID- 2317570 TI - Anti-thoracic duct lymphocyte globulin stimulates human megakaryocytopoiesis in vitro. AB - Anti-thoracic duct lymphocyte globulin (ALG) therapy is effective in patients with aplastic anemia. We examined the effect of ALG on human megakaryocyte progenitor cells (colony-forming unit-megakaryocyte, CFU-Meg) in vitro. Normal human bone marrow mononuclear cells (MNC) were cultured in plasma clots with varying concentrations of ALG or non-immunized horse IgG. After 12 days of culture, significant megakaryocyte colony formation was observed in cultures containing ALG but not in cultures containing non-immunized horse IgG. The peak stimulatory effect seemed to occur with 10-25 micrograms/ml of ALG. When marrow MNC, depleted of adherent and T cells, were cultured in plasma clots with ALG, its stimulatory effect on megakaryocytopoiesis decreased markedly. Finally, it was demonstrated that ALG stimulated marrow MNC to produce a factor stimulatory for CFU-Meg. The in vitro megakaryocytopoietic stimulatory effect of ALG may be related to its clinical efficacy in some patients with aplastic anemia. PMID- 2317571 TI - [The pill and cancer of the breast]. PMID- 2317573 TI - [Symposium. Cancer of the exocrine pancreas. Paris, 6-7 March 1989. Proceedings]. PMID- 2317572 TI - [Role of preoperative radiotherapy in preservation of the anal sphincter in cancer of the lower rectum]. AB - Short term preoperative irradiation of rectal cancer (30 Gy in 12 days) followed by a two-month rest before surgery has proven to be more efficient than most usual protocols of radiotherapy. In a series of 136 tumors T2, T3 or T4, tumor free specimens and Duke'A lesions were found at surgery in 17% and 36% respectively. Surgeons took advantage of the tumor regression and performed sphincter-saving surgery in 41 patients with T2, T3 or T4 tumors of the lower third of the rectum. Of 30 patients followed from 2 to 6 years, the disease-free survival rate is 86%. Only one local failure was observed and subsequently controlled by abdomino-perineal resection. PMID- 2317574 TI - Experimental pancreatic cancer: role of species, sex and diet. AB - Pancreatic cancer has been experimentally induced in rodents by chemical carcinogens that have been used to establish "animal models" for pancreatic carcinogenesis. Recent work with transgenic mice provided a new model in which a dominantly expressed oncogene is transmitted in the germ cell line of homozygous strains. Carcinogens are not equally effective in all species and the histologic type of carcinoma that develops is strongly influenced by the species. Carcinomas that develop in rats and mice are predominantly acinar cell type. In contrast, hamsters characteristically develop duct-like carcinomas. The histologic type of carcinoma in hamsters resembles more closely the majority of carcinomas in the human pancreas than is the case in the rat or mouse. Studies in rats and guinea pigs have demonstrated that duct-like and undifferentiated carcinomas, as well as acinar cell carcinomas, can arise from acinar cells. Thus, the relative importance of ductal cells, centroacinar cells, acinar cells and putative stem cells in the origin of pancreatic carcinomas remains to be determined. In most rat models, males have developed a higher incidence rate of pancreatic cancers than females. Experimental evidence shows that testosterone promotes and estrogen inhibits the growth of preneoplastic lesions and cancers in the rat pancreas. Dietary composition and additives influence carcinogenesis in the pancreas. High fat diets promote carcinogenesis in rats and hamsters, and dietary trypsin inhibitors promote in rats. Other dietary additives such as retinoids and antioxidants have inhibited carcinogenesis in the animal models. PMID- 2317575 TI - [Descriptive epidemiology of cancer of the pancreas]. AB - Cancer of the pancreas is a relatively common malignancy in France, where it represents 10% of all digestive tract cancers. Over the world, there is little variation in incidence rates; Europe, North America, South America, Oceania and parts of Asia represent high risk areas. The regions with the lowest incidence rates are India, mid-western countries and Africa. In most countries, pancreatic cancer incidence rates increased between 1950 and 1965; however little change in incidence has been observed over the past 20 years. Pancreatic cancer occurs more frequently in males than in females in all age groups. No consistent differences have been identified in urban/rural distribution or in socioeconomic status. Studies of migrant populations and some religious groups indicate that environmental factors are of overwhelming importance in determining the incidence of pancreatic cancer in a given population. In the same areas, difference in incidence has been reported among various ethnic groups: in the United States the rate is higher in Blacks than in Whites, in New Zealand in Maoris and Polynesians than in Whites, in Israel in Jews than in non-Jews. This data leads us to the conclusion that diet is of importance in pancreatic cancer etiology. No premalignant lesion has been clearly identified. Particular attention has been paid to diabetes mellitus and chronic pancreatitis, but a firm conclusion cannot be drawn. Some potentially valuable clues for clarifying the etiology of pancreatic cancer have been found by way of descriptive epidemiology. In view of the severe prognosis of the disease, there is an urgent need for further aetiological studies in order to develop effective methods of prevention. PMID- 2317576 TI - [Cancer of the breast in Cote-d'Or (1982-1987). The Burgundian register of gynecologic diseases]. AB - Burgundian registry of gynaecological pathology, formed in 1982 is involved in the study of epidemiologic and clinical features of breast cancer in the district of Cote-d'Or. One thousand two hundred and twenty nine new cases were recorded from 1982 to 1987. Crude incidence was 82.8/100,000 women. Age standardised incidence, based on world standard population was 63.4/100,000 women. Incidence of breast cancer was higher in urban areas (66.0/100,000 women) than in rural (55.0/100,000 women) areas. In comparison with data of other cancer registries, women from Cote-d'Or are in the high risk group. Histological diagnosis was reported in 97% of cases. The most frequent histologic types were infiltrating duct carcinoma (81.6%) and infiltrating lobular carcinoma (4.4%). Non-invasive carcinoma was present in 4.2% of cases; 4.8% of patients presented metastases at the time of primary diagnosis. Sixty four percent of tumors measured less than 30 mm (on gross specimen). Frequency of axillary nodal involvement was lower than 20% for tumors which measured less than 10 mm but increased up to 40% for larger tumors. From a therapeutic point of view, 91% of patients underwent mammary surgery, 67% underwent radiotherapy and 44% underwent chemotherapy and/or hormonotherapy. Five-year observed actuarial survival rate was 68%, corrected 75% and specific 77%. These results point out the necessity of extensive use of mammography for screening of small breast tumors which have a low risk of nodal involvement. PMID- 2317577 TI - [Antigens associated with cancer of the pancreas]. AB - This short review describes the main antigens associated with pancreatic carcinomas: carcinoembryonic antigen (CEA) and related antigens; oncofetal antigens of exocrine pancreas; mucin-type antigens characterized by monoclonal antibodies. PMID- 2317578 TI - [Oncofetal proteins of the exocrine pancreas]. AB - Specific pancreatic oncofetal proteins have been discovered in man and a species of hamster using polyclonal antisera against fetal pancreatic extracts. Two main components in the Mr range of 80 kDa and 58 kDa (hamster) and 110 kDa and 58 kDa (man) were detected in pancreatic fetal extracts, by the "Western blot" technics. Two monoclonal antibodies, namely J28 directed against the human 110 kDa component (FAP protein) and B4 directed against the hamster 58 kDa component (FP protein) have been prepared. The B4 cross-reacts with the homologous human antigen. These monoclonal antibodies have shown that both proteins are antigenically unrelated, although they share common properties such as association to development of exocrine pancreas and high tissue specificity. The expression of both proteins increases in the case of pancreatic cancer but localisation varies. FAP protein is found in peritumoral acinar tissue, whereas FP protein is expressed in transformed cells. FAP protein is a serum marker for pancreatic pathologies and combined with CA 19-9 antigen assay it provides a serum test which is almost specific for cancer of the pancreas with near 100% sensitivity. PMID- 2317579 TI - [A function for carcinoembryonic antigen?]. PMID- 2317580 TI - [Invasive cancer of the uterine cervix in young women: retrospective study of 236 cases]. AB - The study of cases treated between 1970 and 1984 at the Institut Curie, in women aged 40 years and under, was undertaken in order to determine the influence of age on prognosis. The incidence of these cases was stable throughout the 15 years study period as was the very high incidence of earlier cases: 84.5%. Earlier cases were treated with combined radiotherapy and surgery and advanced cases with radiotherapy alone. Overall survival rate was 75% at 5 years, 60% at 10 and 15 years: but 85% for the 36-40 years of age group, 74% for the 30-35 years of age group and 67% for women aged 29 and less. Five year survival rate for operated cases is the same for the 36-40 age group as for all age patients, according to the lymph node status. In contrast, it was 85% in the N-younger group, and 30% for those patients with lymph node involvement. In conclusion, from our study it appears that the overall survival rate for women of 36 years and less, and mainly 29 years and less, is significantly lower than that for older women, and that their prognosis is especially poor in the case of lymph node involvement. PMID- 2317581 TI - [Treatment of cancer of the anal canal with combination radiochemotherapy: apropos of 12 cases]. AB - We present 12 patients (3 male, 9 female) aged from 53-88 years with squamous cell cancer of the anal canal treated with combined radiotherapy-chemotherapy (5 FU-mitomycin C); the distribution of the tumours was 2 T4, 6 T3, 3 T2, 1 T1). In 11 patients evaluated, complete remission was obtained in 8 with partial remission in 2 others. In spite of this good result with combined treatment, 4 patients had a recurrence between 9 and 26 months. Five patients survived and 2 died without disease (16-38 month), 3 patients died and one survived with disease. The small series confirms the efficacy of this combination which treated bulky tumours (T3-T4). It is necessary however to compare these results with radiation alone in a randomised trial. PMID- 2317582 TI - [Geographic distribution of cancer of the larynx and hypopharynx by anatomic subsite]. AB - Incidence data from many cancer registries throughout the world are presented for the major sub-sites of laryngeal and hypopharyngeal cancers. Correlations between glottic (161.0) supra-glottic (161.1) and pyriform sinus (148.1) cancers, and cancers at sites known to be associated with tobacco and alcohol on the one hand, and to annual tobacco and alcohol consumption on the other, are examined. The major role of alcohol in males, suggested by previous studies, is confirmed, but the effect of tobacco does not emerge at population level. PMID- 2317583 TI - [Role of high-dose chemotherapy followed by bone marrow autograft in the treatment of metastatic Ewing's sarcoma in children]. AB - Thirty-two children were treated for metastatic Ewing sarcoma by high-dose chemotherapy followed by autologous bone marrow transplantation. Fourteen patients entered phase II studies of high-dose alkylating agents. The response rate observed was 61%. High-dose chemotherapy was used as consolidation in complete remission of 18 patients. Disease free survival appears to be better than that observed under conventional altered chemotherapy. However, with only 4/18 long term survivors, these results remain unsatisfactory, taking into account the recent encouraging results of semi-continuous conventional chemotherapy. PMID- 2317584 TI - Brief didactic treatment for alcohol and drug-related problems: an approach based on client choice. AB - The conceptual and empirical basis of a treatment programme for the prevention of severe alcohol or drug-related problems is described. The approach rests on the assumption that clients are capable of self-control and of taking responsibility for much of their treatment. We also believe that offering clients choices, particularly about the goal of treatment, is conducive to better outcome. The treatment involves cognitive and behavioural techniques which have been gradually refined in outcome studies with clients of diverse characteristics, and with abstinence or moderation as goals. It is proposed that the treatment model is suitable as a true self-help procedure, or as a brief intervention for primary care health professionals. PMID- 2317585 TI - Crack and cocaine use in south London drug addicts: 1987-1989. AB - There has been great concern in recent years about the abuse of cocaine, particularly in its smokable form 'crack'. This paper presents data drawn from 441 patients seen by a South London Community Drug Team between 1987 and 1989. Only four (1%) cited cocaine abuse as the main drug problem. Heroin was the most common main drug. Detailed information was available on 355 of these subjects. During the study period 63 patients reported using cocaine and the proportion of subjects using cocaine increased from 13% to 29%. Within the sub-group of cocaine users, there was a marked increase in the use of smokable forms of cocaine from 15% in 1987 to 75% in 1989. In view of the increased dependence risk associated with smoking cocaine, this is seen as an ominous development. PMID- 2317586 TI - Consistency of alcohol self-report measures in a male young offender population. AB - The consistency among a number of measures of self-report of alcohol consumption in imprisoned male young offenders was studied by asking 56 young offenders to report, based on a 'typical week', how many days they had consumed alcohol, how many days they were drunk and how much alcohol they had consumed. They were asked to rate their confidence in the accuracy of their self-report and to complete the short EPQ-R, which contains a Lie Scale. Results show that self-report in this population is reliable over time and that different indices of alcohol consumption correlate significantly with each other. Young offenders report a moderate degree of confidence in their accuracy of self-report and the mean EPQ-R Lie Scale score is within 1 standard deviation of the norm for a comparable sample. PMID- 2317587 TI - Liver cirrhosis with and without mention of alcohol as cause of death. AB - Changes in the estimated proportion of liver cirrhosis deaths attributable to alcoholism in the United States from 1940 to 1980 are reviewed. The value of this proportion from 1940 in the original Jellinek Alcoholism Estimation Formula, through Formula modifications, to 1980 use are presented; the rationale for various changes in its value are discussed. Essex County, New Jersey, USA decedents in 1984, aged 25-years or older, whose underlying cause of death was specified alcoholic cirrhosis and those who died of cirrhosis without mention of alcohol are analyzed for differences in background and post-mortem characteristics. Some appreciable proportion of cirrhosis deaths without mention of alcohol is considered to be attributable to alcoholism. Background and post mortem differences between persons whose underlying cause of death is certified as cirrhosis with and without mention of alcohol suggest some bases for the under reporting of specified alcoholic cirrhosis mortality. PMID- 2317588 TI - Evaluation of an alcohol education package for non-specialist health care and social workers. AB - A quasi-experimental non-equivalent control group design was used to assess the influence of a two-day experiential alcohol education package for non-specialist health care and social workers. Four pairs of teams took part in the study: general practice; accident and emergency; medicine for the elderly; and social work. The dual foci of the evaluation were agents' knowledge and attitudes, and these were assessed using a modified version of the Alcohol and Alcohol Problems Perception Questionnaire (AAPPQ). For both variables, the one-month follow-up scores of the education teams were significantly higher than those of the comparisons, although the effect was stronger in the case of therapeutic attitudes than knowledge. There were also significant differences in improvement in attitude scores, with significant effects being observed in the general practice, medicine for the elderly and social work teams but not the accident and emergency. At 6 months, the level of fall-off in improvement varied and this, along with the pattern of change evident in the five components which comprise the AAPPQ attitude scale, was examined and discussed in relation to previous research in this field of inquiry. PMID- 2317589 TI - Help-seeking and referrals in a needle exchange: a comprehensive service to injecting drug users. AB - From November 1987 to March 1989 total number of clients, visits made, including numbers of new clients and second visits, and referrals to other agencies were routinely monitored at The Cleveland Street Needle Exchange, the Middlesex Hospital, London. During the study period a total of 510 onward referrals were made, involving 277 clients. Of these, 305 (59.7%) were to drug agencies and 187 (36.7%) to medical services. A sample of clients were interviewed to identify demographic and behavioural characteristics. Comparisons were made between those clients receiving referrals and the general client population; no significant differences were found in terms of sex, age and current patterns of drug use. However, those who accepted and took up referrals were found to have begun opiate use, injecting drug use and daily injecting at an earlier age than the general client population. The scheme attracts and retains its clients and provides a comprehensive service to a client group not currently in contact with other services. PMID- 2317590 TI - Dyschromatopsia in heroin addicts. AB - The Farnsworth-Munsell 100-hue test was employed to determine whether there was any defect of colour vision in 29 confirmed male heroin addicts who had been successfully detoxified. Forty age-matched males served as controls. A typical normal error score on the FM test is about 40 and an error score of over 100 indicates poor colour discrimination; 86.2% of the eyes of the control group had an error score below 100 while only 17.2% of the eyes of heroin addicts had an error score below 100. The colour confusion among the heroin addicts was in the blue-purple (475-495 mu) range. These results indicate that colour vision defects are more common in heroin addicts. PMID- 2317591 TI - Tobacco use: a perspective for alcohol and drug researchers. PMID- 2317592 TI - What does research on nicotine and tobacco use have to offer alcohol researchers? PMID- 2317593 TI - Licit and illicit drug policies: a typology. AB - To foster comparison of policy interventions across the various categories of licit and illicit drugs, we develop a typology of policies intended to address drug abuse problems. The principal dimensions of the typology are policy type and intervention channel. While the typology has important limitations, as a mechanism to organize information and stimulate thought it holds the potential to improve understanding of commonalities and distinctions among policies applying to widely discrepant drug problems, both within and across cultures. As such, it could contribute to the development of more effective approaches to grappling with a diverse set of drug policy issues. PMID- 2317594 TI - Mass and molecular weight of isolated nuclear rings. AB - Nuclear rings are cell structures found at the nuclear cortex wedged between the nuclear envelope and the chromatin fiber network. In previous publications we have dealt with their morphology, relationships with the nuclear membranes, chromatin fibers and cytoskeletal filaments; and more recently, with their measurements at high electron microscope resolution. In this article we have calculated the mass and molecular weight of 336 isolated nuclear rings from human circulating lymphocytes using a photometric procedure and polystyrene latex spheres as the standard for weight calibration. Our results show a range of mass of 0.4-35.5 x 10(-16) g (equivalent to 0.2-21.2 x 10(8) Da with a positively skewed distribution (median: 3.3 x 10(-16) g or 2.0 x 10(8) Da). Mass and volume of nuclear rings were highly correlated. In addition, it was possible to calculate the area, the whole mass and the mass per unit area of the nuclear envelope present in the center of the nuclear rings. The mass of this area also shows a lognormal distribution (median of mass/unit area: 37.3 x 10(-8) pg/nm2 or 1.9 x 10(5) Da/nm2). We discuss the significance of this results as parameters for the characterization of the nuclear rings and their possible implications for a new interpretation of nuclear cortex architecture, nucleocytoplasmic traffic and macromolecule segregation between the two main cell compartments. PMID- 2317596 TI - The culture of human skin fibroblasts on microcarriers in the presence of serum substitute: Ultroser G. AB - The effects of the substitution of serum by Ultroser G on human skin fibroblasts cultured on microcarriers were analysed. Cultures could not be established on microcarriers in the presence of Ultroser G. However, microcarrier cultures started in the presence of 10% foetal calf serum, and transferred to 2% Ultroser G after 7 days resulted in high cell densities. PMID- 2317595 TI - Permeability of the normal rat brain, spinal cord and dorsal root ganglia microcirculations to immunoglobulins G. AB - The distribution of blood-borne immunoglobulins G (IgG) was studied in the cerebral cortex, pineal gland, spinal cord and dorsal root ganglia of normal Lewis rats using the detection of autologous anti-horseradish peroxidase (HRP) antibodies. This detection was performed by means of light and electron microscopy. This study demonstrated that, in the cerebral cortex and the spinal cord microcirculations, endothelial cells are a restrictive barrier against IgG while IgG are able to diffuse into the perivascular parenchyma of the pineal gland and spinal ganglia. PMID- 2317597 TI - Magnitude of diotic summation in speech-in-noise tasks: performance region and appropriate baseline. AB - The diotic summation effect is one of the three types of binaural advantage for perceiving speech-in-noise. Using a within-subject design in normally-hearing subjects having no significant noise exposure, we examined its magnitude. The average advantage was +5%, at an overall performance level of 70-80% rising to +9% when an appropriate control was used to exclude order effects introduced by the within-subject design. Diotic summation is an important component of the advantage to be derived from presentation to two ears, but the size of the binaural advantage obtained depends critically on the particular monotic baseline chosen for comparison. The methodological problems of demonstrating binaural advantages (as in binaural aiding studies) are discussed. PMID- 2317598 TI - The GMC project: some linguistic and cognitive characteristics of a population of hearing-impaired children. AB - In this paper, some developmental characteristics of a population of hearing impaired children are described. The 79 children described are all those born in Greater Manchester in the years 1977-1980 with a mean bilateral sensorineural hearing loss of 25 dB HL or more in the better ear and without additional handicaps or bilingualism in the home. The subjects attended clinics in which comprehensive monitoring of their development was carried out by means of audiological, psychological and linguistic testing and video-recordings of mother child interaction. In this cross-sectional study of their first clinic attendance at the ages of between 3 and 7, the measures used to define their levels of language ability and intelligence are described. As a means of dealing with the wide range of values, the children were blocked into groups according to their spontaneous language level and the results are reported groupwise. PMID- 2317599 TI - A procedure for measuring auditory and audio-visual speech-reception thresholds for sentences in noise: rationale, evaluation, and recommendations for use. AB - The strategy for measuring speech-reception thresholds for sentences in noise advocated by Plomp and Mimpen (Audiology, 18, 43-52, 1979) was modified to create a reliable test for measuring the difficulty which listeners have in speech reception, both auditorily and audio-visually. The test materials consist of 10 lists of 15 short sentences of homogeneous intelligibility when presented acoustically, and of different, but still homogeneous, intelligibility when presented audio-visually, in white noise. Homogeneity was achieved by applying phonetic and linguistic principles at the stage of compilation, followed by pilot testing and balancing of properties. To run the test, lists are presented at signal-to-noise ratios (SNRs) determined by an up-down psychophysical rule so as to estimate auditory and audio-visual speech-reception thresholds, defined as the SNRs at which the three content words in each sentence are identified correctly on 50% of trials. These thresholds provide measures of a subject's speech reception abilities. The difference between them provides a measure of the benefit received from vision. It is shown that this measure is closely related to the accuracy with which subjects lip-read words in sentences with no acoustical information. In data from normally hearing adults, the standard deviations (s.d.s) of estimates of auditory speech reception threshold in noise (SRTN), audio-visual SRTN, and visual benefit are 1.2, 2.0, and 2.3 dB, respectively. Graphs are provided with which to estimate the trade-off between reliability and the number of lists presented, and to assess the significance of deviant scores from individual subjects. PMID- 2317600 TI - Computer simulation of the patient for training in audiometry. AB - A theoretical framework for computer simulation of the listener's response during pure tone audiometry is described. Methods for providing features which make the simulation realistic are discussed. PMID- 2317601 TI - Predictors of tinnitus discomfort, adaptation and subjective loudness. AB - In a nation-wide investigation, covering all the hearing centres in Sweden, a study was made of adaptation processes, subjective discomfort from tinnitus, subjective loudness of tinnitus and psychological complaints in 3372 subjects by means of a questionnaire. The most important predictors of discomfort from and adaptation to tinnitus were found to be the controllability and the degree of maskability by external sounds, i.e. the subject's coping abilities or internal external locus of control. Increased control and masking effects from the environment imply a decrease in discomfort and better adaptation. The most important predictor of worsened subjective loudness of tinnitus was the duration of the tinnitus. That is, subjects who had had tinnitus for a longer time perceived the loudness as more intense. The psychosomatic factors which most strongly predicted increased discomfort from and decreased tolerance to tinnitus were depression and insomnia. These findings have theoretical and practical implications for the management and treatment of tinnitus. PMID- 2317602 TI - Response times to speech stimuli as measures of benefit from amplification. AB - The benefits of management of hearing disability, in particular by provision of a hearing aid, are traditionally assessed by the percentage improvement in performance on a speech identification task. To provide precise and stable results, such procedures require more time than is available in most clinical settings. In any stressed performance, e.g. an impaired individual trying to listen in noise, there is a trading relationship between accuracy and effort (the cost at which accuracy is achieved). If the control of performance naturally spends effort to stabilize high performance, then benefit from amplification may essentially comprise and be measurable as reduction in effort rather than improvement in accuracy. Certainly complaints of hearing disability emphasize fatigue from careful listening. Hence a hearing aid may not only enable hearing impaired persons to hear more of speech but may enable them to hear it more easily, thus reflecting a second dimension to disability and benefit. Ease of listening was investigated using auditory response times to speech stimuli of two levels of structure: single words and sentences. The speech material was presented to 44 experienced hearing aid users (mild to moderate sensorineural hearing impairment). The speech was presented both unaided and aided at presentation levels of 60, 70 and 80 dB SPL and signal-to-noise ratios of quiet and + 5 dB. Response times were taken to the tokens within each list that were correctly identified. Benefit is defined as the decrease in response time from the unaided to the aided condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317603 TI - Macrophage differentiation at the genome level: studies of lysozyme gene activation. PMID- 2317604 TI - Immunotherapy in conjunction with autologous bone marrow transplantation. AB - Although high-dose chemoradiotherapy used for conditioning prior to autologous bone marrow transplantation (BMT) represent an effective tool for eradication of certain malignant hematological disorders, relapses indicate that the last tumor cell is unlikely to be completely eradicated. We are investigating several approaches for controlling residual tumor cells escaping from chemoradiotherapy by cellular adoptive immunotherapy and amplification of natural defense mechanisms, using recombinant human IL2 (Cetus, Emeryville CA), in a murine model of leukemia/lymphoma disease (BCL1). PMID- 2317605 TI - Impact of the White Paper on teaching and training. PMID- 2317606 TI - The Dowie report: is it out of date? PMID- 2317607 TI - Organ transplant units: future needs. PMID- 2317608 TI - The life of heart valves. PMID- 2317609 TI - Acipimox and hypertriglyceridaemia. PMID- 2317611 TI - NHS indemnity scheme: bad news for doctors. PMID- 2317610 TI - Do overseas doctors receive appropriate training? PMID- 2317612 TI - An alternative to bougies for difficult intubation. PMID- 2317613 TI - Not so rare complications of pulmonary AVMs letter; [comment]. PMID- 2317614 TI - Successful cannulation of the subclavian vein. PMID- 2317615 TI - What size chest tube for pleural effusions? PMID- 2317616 TI - Can communication skills be taught? AB - Basic interviewing skills can be learned at undergraduate and postgraduate level, providing effective methods are used. These include demonstration of key skills, practice under controlled conditions, and audiotape or videotape feedback of performance by a tutor within small groups. More complex skills can also be learned but may not be used or maintained without ongoing training and supervision. PMID- 2317617 TI - Medical negligence law: 1. Liability and litigation trends. PMID- 2317618 TI - How to aspirate the pericardium. AB - Of the practical procedures in a general physician's repertoire, pericardiocentesis is one of the less commonly performed and perhaps among the most worrying. The advent of echocardiography has made the procedure safer but it must be appreciated that the risk of developing a life-threatening complication is probably still higher than during cardiac catheterization or coronary angiography. PMID- 2317619 TI - Aspirin and intravenous regional blocks. PMID- 2317621 TI - Motherhood, employment and the development of depression. A replication of a finding? AB - A prospective inquiry of a largely working-class sample of women with children considers the effect of employment on risk of developing clinical depression. The hypothesis was that there would be a direct protective effect arising from employment once quality of other support was taken into account. In fact full time working mothers were at high risk. This appeared to be explained by either prior work strain or a severe event involving 'deviant' behaviour on the part of husband/boyfriend or child. Neither factor was relevant for part-time workers. The severe events appeared to be particularly depressogenic for full-time workers because they represented either failure in the motherhood role or a sense of entrapment in an unrewarding work/domestic situation. However, those in part-time work had a low rate of onset compared with non-workers, and the difference appears to be related to non-working women feeling less secure about their marriages. PMID- 2317622 TI - First-rank symptoms of Schneider. A new perspective? AB - Based on evidence from patients with epilepsy who develop a schizophrenia-like illness, it is argued that the first-rank symptoms of Schneider are closely related to temporal lobe pathology, particularly in the dominant hemisphere. It is suggested that the first-rank symptoms should be seen as signifiers of temporal lobe pathology, as opposed to being pathognomonic for schizophrenic illness. PMID- 2317623 TI - Cognitive processing and its relationship to symptoms and social functioning in schizophrenia. AB - This study analyses the relationship between contextual processing ability and symptom and social status in schizophrenia. The results showed that current symptom status is related to occupational status, and contextual processing is related to current symptom status and employment history. Current symptom severity in chronic schizophrenics may indicate an increased frequency and/or duration of symptom episodes in the past, and therefore an increase in the periods in which contextual processing was disturbed, which would therefore account for the observed decrease in work achievements. PMID- 2317620 TI - Proceedings of the British Pharmacological Society Meeting. 3rd-5th January 1990. Abstracts. PMID- 2317624 TI - Linguistic performance in schizophrenia: a comparison of acute and chronic patients. AB - A computer-assisted analysis of samples of free speech from acute schizophrenics (n = 50), chronic schizophrenics (n = 27) and normal subjects (n = 50) enabled a comparison of the linguistic profiles of the three groups. The chronic group consistently emerged as the most impaired, on measures of complexity, integrity (error) and fluency of speech, with the acute patients performing less well than normal speakers but better than chronic patients. Demographic differences could account for only a small number of the linguistic differences. A comparison of chronic schizophrenics from the community and those from long-stay wards suggested that their poor linguistic performance was in some way related to the illness process and not to institutionalisation. Three possible explanations for these results were considered, particularly the possibility that low complexity of speech, negative symptoms and poor outcome are in some way related. PMID- 2317625 TI - Re-examination of the language of psychotic subjects. AB - To investigate whether language in schizophrenia deteriorated progressively, 11 schizophrenic subjects, 9 manic subjects and 9 controls were re-tested after an interval of three years using the computer-assisted syntactical analysis technique of Morice. In 13 of the 16 linguistic variables described as hallmarks of schizophrenic speech decline, deterioration was noted in schizophrenics in the direction predicted and relative to the manic and control groups. The deterioration was most pronounced in complexity and integrity of speech. One variable remained unchanged and two (semantic variables) showed marginal improvement. It was concluded that language, and in particular syntax, does deteriorate in the schizophrenic process. PMID- 2317626 TI - Glucose metabolic rate in normals and schizophrenics during the Continuous Performance Test assessed by positron emission tomography. AB - Local cerebral uptake of glucose labelled with fluorine-18 was measured by positron emission tomography in 13 patients with schizophrenia and 37 right handed volunteers. Patients received no medication for a minimum of 31 days and a mean of 30 weeks. The subjects were administered the labelled deoxyglucose just after the beginning of a 32-minute sequence of blurred numbers as visual stimuli for the Continuous Performance Test. In normal controls, task performance was associated with increases in glucose metabolic rate in the right frontal and right temporoparietal regions; occipital rates were unchanged. Patients with schizophrenia showed both absolutely and relatively reduced metabolic rates in the frontal cortex and in the temporoparietal regions compared with normal controls. PMID- 2317627 TI - Handedness and epileptic schizophrenia. AB - Thirty-two epileptic patients with RDC diagnoses of schizophrenia were tested for handedness on the Annett Handedness Schedule, and handedness was assigned on the basis of Annett-Maudsley criteria. They were compared with three other groups of patients. Five (15.6%) of the epileptic schizophrenic patients were mixed or left handed. The prevalence of mixed and left handedness did not differ between the samples studied. However, there was a significant reduction of mixed and left handedness in male epileptics with schizophrenia. Mixed or left handedness in male epileptics appears to be protective against the development of psychiatric illness in general. PMID- 2317628 TI - A study of epileptic psychosis using magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) was used in patients with epilepsy and psychosis. From 50 patients with epilepsy, a subgroup of 12 patients were categorised by the Present State Examination (PSE) as having nuclear schizophrenia (NS) and then compared with an epileptic control group with no psychiatric history. Further, patients with hallucinations were compared with patients without hallucinations. No differences in T1 relaxation times in any regions of interest were noted in the NS group compared with the other group. However, patients with hallucinations had a significantly higher T1 value in the left temporal lobe. These findings support the concept that specific abnormalities in limbic system structures relate to the phenomenology of the psychoses of epilepsy, especially left temporal lobe epilepsy. PMID- 2317629 TI - Characteristics of suicide attempters in a population-based sample of Dutch adolescents. AB - The characteristics of suicide attempters were ascertained in a sample of 9393 Dutch students aged 14-20. Broken homes and use of drugs and alcohol were found more often among attempters. Attempters more frequently lived with a single parent, in children's homes or foster homes, were disproportionately of female sex, reported more deaths of friends or relatives, and more often had an unemployed father. Thoughts of suicide and of death were reported more frequently, they were more depressed and hopeless, and had less self-esteem. They were less rational and perceived relationships with parents as poor. PMID- 2317630 TI - Adult children of problem drinkers in an urban community. AB - In a medium-sized Canadian city, 581 randomly selected households were contacted and responded to a survey on the impact of parental alcohol problems. Twenty-two per cent of the respondents indicated that at least one of their parents had a drinking problem. The biological father was affected in 81%. Compared with the rest of the sample, the adult children of problem drinkers were younger but they did not differ in income or education. Adult children of problem drinkers were more likely to have parents who were divorced or separated; to be divorced, separated, or remarried themselves; to be heavy drinkers and have indications of alcohol problems; and to use more sources of help for problems with stress and anxiety and problems with alcohol. They did not differ from those without parental drinking problems on measures of current positive and negative affect. PMID- 2317631 TI - Olfactory delusional syndrome with various aetiologies. AB - Six patients who had delusional convictions that they were malodorous were followed up for between six months and four years. Difficulties encountered in clinical settings in differentiating overvalued ideas, delusions, and hallucinations arise from lack of clarity of psychopathological terminology. Schizophrenia and depression are closely related to the syndrome. PMID- 2317632 TI - Personality disorder and psychiatric illness in general practice. AB - In a one-year prevalence study of conspicuous psychiatric morbidity in two group general practices, one urban and the other rural, personality disorder was diagnosed in 5.3% by the GP and in 5.6% by the psychiatrist, but this increased to 28% when personality disorder was assessed using a structured interview. The prevalence of personality disorder was higher in the urban practice than in the rural one but there was no consistent association between personality disorder and mental state disorder, with the exception of alcohol abuse and dependence. The high rate of personality disorder found using the interview schedule is likely to be a true finding, and failure to recognise this hidden morbidity is important in both general and psychiatric practice. PMID- 2317633 TI - Nicotine and Alzheimer's disease. PMID- 2317634 TI - Carbamazepine in affective disorders. PMID- 2317635 TI - Is screening for syphilis justified? PMID- 2317636 TI - Genetics of alcoholism. PMID- 2317637 TI - Akathisia. PMID- 2317638 TI - Asneezia. PMID- 2317639 TI - Psychosis in a transsexual. PMID- 2317640 TI - Validation of a self-administered urological questionnaire. AB - Self-administered questionnaires are widely used in clinical practice and as an aid to research. However, their reliability as a means of eliciting symptoms of urological disease has not been established. A questionnaire designed to elicit symptoms of urological disease was validated in 120 patients (36 out-patients, 27 in-patients and 57 community patients). All found the questionnaire acceptable and the completion rate was 99%. Only 3 of 648 answers were changed on the test retest analysis. Consistency, as assessed by a comparison of responses by clinician and patient, was satisfactory in 11 of 15 questions relating to urological symptoms and the questionnaire successfully identified a high risk group of patients from the community requiring further urological evaluation. The need to include results of a preliminary validation study when reporting results obtained by a self-administered questionnaire is emphasised. PMID- 2317641 TI - Pyelo-intestino-cutaneous conduit in the treatment of renal carcinoma of solitary kidneys. AB - A pyelo-intestino-cutaneous conduit, either by colonic or ileal segment, was used successfully in 4 patients with urothelial carcinoma affecting a solitary kidney. Primary healing was good but involved the risk of stricture formation. During the follow-up period (10-48 months), repeated endoscopic check-ups were easily performed through the conduit, enabling coagulation of recurrent tumour growth. Two patients are still alive and well; 2 are dead. PMID- 2317642 TI - Antegrade ureterolitholapaxy in the treatment of obstructing or incarcerated proximal ureteric stones. AB - Extracorporeal shockwave lithotripsy (ESWL) and retrograde ureterorenoscopy (RU) have transformed the management of ureteric calculi. Nevertheless, patients with obstructing proximal ureteric calculi are not suitable for ESWL or RU. From January 1986 to September 1988, 17 patients with fixed upper ureteric stones underwent antegrade renoureteroscopy and percutaneous surgery. The technique was effective in removing incarcerated proximal ureteric calculi: all patients were stone-free at follow-up 3 months later. PMID- 2317643 TI - Transurethral ureterorenoscopic lithotripsy and retrieval of ureteric calculi under local anaesthesia and sedation. AB - Under strict indications, ureterorenoscopic (URS) lithotripsy was used to treat ureteric calculi in 61 patients under local anaesthesia and sedation in a 2-year period ending November 1988. Assessments of success and discomfort of the procedure were made. Stone retrieval was accomplished in 48 patients (78% success rate) and a mean pain score of 6 was recorded in a scale from 0 to 10. It was concluded that performing URS under local anaesthesia is an acceptable alternative. PMID- 2317644 TI - Vesicoureteric reflux in the adult male. AB - The main prevalence of vesicoureteric reflux (VUR) is in the adult female population. Although recognised as a clinical entity in adult males, little detailed information is available on this subject. A retrospective analysis was carried out on the results of 1519 consecutive videocystometrograms performed on male patients. VUR had an overall incidence of 8.6% within this population, with a range of 5.1% in patients with normal urodynamics to 15.6% in those with detrusor-sphincter dyssynergia. The common denominator between VUR and urodynamic measurement appears to be the generation of high intravesical pressures. These findings suggest that VUR is not uncommon in the male population, is usually asymptomatic and should respond to the treatment of any underlying bladder abnormality. PMID- 2317645 TI - Acquired venous disease of the lower urinary tract. AB - Thrombosis of the vena cava, femoral veins or iliac veins can result in the formation of large collateral veins in the pelvis and retroperitoneum which are often asymptomatic but which may cause severe bleeding and produce major difficulties in urological management. Such abnormalities are a rare cause of urological symptoms but may be difficult to diagnose unless a high index of suspicion is maintained. Three patients are reported who developed significant urological problems as a consequence of acquired venous disease; the use of ultrasound, venography and CT in the diagnosis of this condition is described. PMID- 2317646 TI - Measurement of voiding pressures on ambulatory monitoring: comparison with conventional cystometry. AB - A series of 20 patients underwent conventional medium fill cystometry (CMG) and ambulatory monitoring during natural bladder filling (AM). The measurement of voiding pressures by the 2 techniques was compared. The maximum subtracted detrusor contraction pressure recorded during CMG (50 +/- 30 cm H2O) was significantly less than that recorded during AM (86 +/- 35 cm H2O). Voiding pressures during natural filling are greater than those observed during conventional urodynamic studies: this finding may have important implications in the definition of bladder outflow obstruction. PMID- 2317647 TI - Voiding patterns in men evaluated by a questionnaire survey. AB - A questionnaire on obstructive and irritative voiding symptoms was sent to 572 men aged between 20 and 79 years, selected at random from the National Register; 337 questionnaires were completed. None of the responders had consulted a doctor because of voiding symptoms. There was a significant increase in voiding symptoms and in the obstructive, irritative and total symptom scores between the sixth and seventh [corrected] decades, whereas the increases in the other decades were small. Only the prevalence of terminal dribbling was uniform. The prevalence of single obstructive and irritative voiding symptoms in men aged 60 to 79 years without subjective prostatism was the same as in patients admitted with prostatism, although most of the men had milder symptoms. Only nocturia and urge incontinence were more prevalent in patients admitted with prostatism. About 20% of men in the oldest decades had symptoms equal in severity to those found in men undergoing prostatectomy; 29% and 11% of men in the eighth decade [corrected] had nocturia twice and 3 times or more respectively; 19% complained of urge incontinence. More information on possible treatment is needed. PMID- 2317648 TI - Assessment of the poorly contractile or acontractile bladder in the older male in the absence of neuropathy. AB - Up to 30% of patients who undergo prostatectomy are left with residual symptoms. Most have persistent detrusor instability, but some have poorly contractile or acontractile bladders. Over a 2-year period, 42 neurologically normal patients were shown to have a hypocontractile or acontractile bladder on urodynamic testing; 27 had undergone outflow tract surgery. Four patients who were totally incontinent had undergone at least 2 transurethral resections. The remainder had severe frequency, urgency and nocturia. Urodynamically, all but 7 patients with poor compliance had normal filling cystometrograms, all but 8 had residual urine volumes less than 100 ml, and 26 had less than 5 ml. Thus their symptoms are difficult to explain. Apart from the insertion of an artificial sphincter in those with total incontinence, treatment did not improve any of these patients. PMID- 2317649 TI - Surgical management of the congenital neuropathic bladder. AB - We have previously described 3 types of lower urinary tract dysfunction in the congenital neuropathic bladder--contractile, intermediate and acontractile- accounting for 35, 40 and 25% of patients respectively. Subsequent urodynamic and surgical experience has shown that the intermediate type is commoner and the acontractile type less common than was thought. The contractile group accounts for 31% of patients and rarely requires surgery (a "clam" ileocystoplasty). The acontractile group accounts for only 9% but more commonly requires surgical treatment, usually the implantation of an artificial urinary sphincter (AUS). The intermediate group accounts for 60% of patients and usually requires surgery. If there is no significant sphincter weakness incontinence, a "clam" ileocystoplasty alone is performed; if there is sphincter weakness, a "clam and a cuff" procedure is performed with implantation of the remainder of the AUS at a later date, if required. PMID- 2317650 TI - Follow-up results with the Stamey operation for stress incontinence of urine. AB - Medium-term results are reported in 100 patients who had a Stamey operation for genuine stress incontinence. The results were good in 72, improved in 8 and 20 were failures when assessed clinically and with pad tests. Most of the failures occurred in the first post-operative year. A repeat Stamey operation was easy and the results have been good in 7 of the 8 cases. Bladder outflow obstruction, urinary infection and wound sepsis were not a problem. PMID- 2317651 TI - The Stamey endoscopic bladder neck suspension in the elderly. AB - The Stamey procedure was performed on 21 women aged 65 to 81 years; 17 were cured (completely dry) or significantly improved (maximum 1 pad/day). Urethral length was significantly increased by the operation but maximum urethral pressure and maximum flow rate were unchanged. Complications were few. PMID- 2317652 TI - Immunohistochemical staining with monoclonal antibody 32-2B to desmosomal glycoprotein 1. Its role in the histological assessment of urothelial carcinomas. AB - A series of transitional cell carcinomas of bladder were stained immunohistochemically with the monoclonal antibody, 32-2B, to desmosomal glycoprotein 1. All of the sections showed positive staining with the antibody. Assessment of staining intensity, by 3 independent examiners, revealed a strong negative correlation between density of desmosomal staining and degree of invasion (P = 0.012). Nests of strongly staining cells were identified in several invasive tumours, possibly indicating early squamous differentiation. Invasive tumour cells in the subepithelial stroma also stained strongly with the antibody. Correlation with clinical course, however, revealed no significant association between desmosomal staining and the incidence of recurrence or progression. It is suggested that staining with this antibody may be of value in detecting both stromal invasion and early squamous differentiation of transitional cell carcinomas. Both this and previous studies emphasise the value of this antibody as an epithelial marker in neoplasia. PMID- 2317653 TI - Defective interleukin-1 production of monocytes in patients with bladder cancer. AB - Patients with advanced malignant neoplasms have a variety of abnormal lymphocyte and monocyte functions. We examined the PHA (phytohaemagglutinin) blastogenic response of lymphocytes and interleukin-1 (IL-1) production of monocytes in 40 bladder cancer patients and 16 control subjects. The correlation between the 2 parameters was also studied. The PHA blastogenic response was measured by the incorporation of 3H-thymidine into lymphocytes. IL-1 production was assayed by the murine thymocyte 3H-thymidine incorporation assay. As a result, the PHA blastogenic response and IL-1 production were significantly lower in the high stage bladder cancer patients compared to the control subjects and low stage patients. However, there was no significant correlation between the 2 parameters. Furthermore, with the addition of indomethacin, IL-1 production in the control subjects and low stage patients improved to the same degree, but it did not reach the control level in the high stage patients. PMID- 2317654 TI - Influence of retinoids on bladder cancer growth as detected by primary tissue culture. AB - The ability of the retinoid compounds, all-trans and 13-cis, to inhibit the growth of bladder tumour cells was investigated in primary tissue culture. A significant decrease in tumour growth was evident in 9 human bladder cancer patients. Since retinoid compounds are able to delay the progression or induction of tumours in primary tissue culture, their trial use as intravesical agents may be warranted. PMID- 2317655 TI - Life with urostomy. AB - The quality of life of urostomy patients was assessed by direct interview. Specific problems, such as urine leakage, were documented and the size, site and quality of the stoma were assessed. The study included 41 patients; 83% noted an improvement in the quality of life since their urinary diversion and 90% were still able to work or continue to perform household duties. Urine leakage was the commonest problem and this was unrelated to the length of the stoma or the build of the patient. More important factors were the correct siting of the stoma and the avoidance of parastomal herniation. All patients emphasised the importance of the stoma therapist. PMID- 2317656 TI - Prostatic stenting for outflow obstruction. AB - A series of 30 patients with outflow obstruction underwent treatment with prostatic stents. Most had retention of urine and were unfit for conventional surgery. The prostatic stent was readily inserted under local anaesthesia and successfully relieved obstruction in 80% of patients with acute retention. Minor problems were common but there were few major complications. PMID- 2317657 TI - Sperm motility, velocity and migration. AB - Four different methods for evaluating sperm motility were analysed for experimental error: subjective assessment of a wet film preparation, sperm velocity measured by time-lapse photography, sperm velocity measured by computer analysis and sperm migration across a nucleopore membrane. Subjective assessment of motility was found to be inaccurate, within single observer and between 2 observers. Both methods of measuring mean sperm velocity were accurate, particularly that using the computer analysis system; a high technical failure rate was found using time-lapse photography. Sperm migration across a nucleopore membrane was found to be highly inaccurate. Two groups were then analysed for the predictive value of these tests (excluding sperm migration): 104 proven fertile men and 53 infertile men. Although subjective motility was able to predict from which group the sample came at optimum cut-off with 78% accuracy, computer analysed sperm velocity could predict with overall 91% accuracy at optimum cut off. Computer analysis of sperm velocity offers a rapid, objective and predictive assessment of sperm function. PMID- 2317658 TI - The scrotoscope. A new instrument for examining the scrotal contents. AB - A new instrument (the scrotoscope) is described. It was used in the diagnosis of questionable masses in the testis, epididymis and spermatic cord in 49 patients. Scrotal examination and testicular biopsy were performed in 31 infertile patients by means of the scrotoscope, together with pampiniform plexus venography in 1 patient and vasography in 2. Scrotoscopy allows the surgeon to view, study and treat intrascrotal lesions. PMID- 2317659 TI - Infected hydrocele following acute appendicitis. PMID- 2317660 TI - Squamous metaplasia complicating a mullerian duct remnant. PMID- 2317661 TI - A rare cause of post-micturition dribbling: incomplete urethral duplication. PMID- 2317662 TI - Refrigeration engineer's testis. PMID- 2317663 TI - Squamous cell carcinoma in a patient on clean intermittent self-catheterisation. PMID- 2317664 TI - Fibroepithelial polyps of the pelviureteric junction in childhood. PMID- 2317665 TI - Ruptured bladder following circumcision using the Plastibell device. PMID- 2317666 TI - Primary squamous carcinoma of the male urethra presenting as a periurethral abscess. PMID- 2317667 TI - Simple method of hydrostatic dilatation of the ureter for ureteroscopy. PMID- 2317668 TI - The Emeltract mechanized surgical retractor. PMID- 2317669 TI - Peroperative observation of marginal artery bleeding: a predictor of anastomotic leakage. PMID- 2317670 TI - Familial megaduodenum associated with hypoganglionosis. PMID- 2317671 TI - Blood transfusion and survival following surgery for prostatic carcinoma. AB - Blood transfusion in the perioperative period has been reported to have a detrimental effect on survival in many types of cancer. Other studies have failed to confirm this. We have examined retrospectively the records of 246 patients with prostatic carcinoma who underwent transurethral resection of the prostate (TURP) in Aberdeen Royal Infirmary between 1977 and 1982. Bilateral orchiectomy (BLO) was performed in 193 patients. Of these patients, 71 of 246 (29 per cent) received perioperative blood transfusion. After controlling for differences due to a number of variables, transfusion of non-autologous blood was shown to be associated with a significant negative effect on survival. Perioperative transfusion of non-autologous blood should be avoided in patients with malignancy, unless there are clear overriding clinical indications. Prospective trials are needed urgently. PMID- 2317672 TI - Sutured posterior abdominal rectopexy with sigmoidectomy compared with Marlex rectopexy for rectal prolapse. AB - Two treatment policies for rectal prolapse were prospectively assessed between April 1986 and January 1989. Sixteen patients had a Marlex mesh posterior rectopexy alone and 13 underwent a sigmoidectomy combined with a sutured posterior rectopexy. Preoperative and post-operative assessment included manometry, a saline infusion test and video-proctography. Hospital stay, control of prolapse and complications were comparable in both groups. Restoration of continence occurred in nine of the 12 incontinent patients after Marlex rectopexy, compared with six of nine after sutured rectopexy and sigmoidectomy. Constipation persisted in three patients who were constipated before operation and in four of 13 who had previously normal bowel habits became constipated after Marlex rectopexy; constipation persisted in one of five previously constipated patients while none with previously normal bowel habits became constipated after sutured rectopexy and sigmoidectomy. Sigmoidectomy combined with sutured rectopexy was safe and as efficient as Marlex rectopexy in prolapse control and improvement of continence; significantly fewer patients were constipated (one of 13) after sigmoidectomy than following rectopexy alone (seven of 16). A randomized trial now seems justified. PMID- 2317674 TI - Surgical correction of the efferent ileal limb for disordered defaecation following restorative proctocolectomy with the S ileal reservoir. AB - The S ileal reservoir has been superseded in this unit but 76 patients had this operation between 1976 and 1983. Forty-one (54 per cent) patients had to catheterize the reservoir to evacuate faeces and this was primarily due to the long efferent ileal limb. In six patients, the need to catheterize and other problems with defaecation were such that surgical correction of the efferent ileal limb was undertaken. These six patients are reported. Presenting features were the need to catheterize the reservoir, difficulty in catheterizing, faecal incontinence, stenosis of the efferent ileal limb and transanal prolapse of the efferent ileal limb. All patients had an excessively long efferent ileal limb of 8 cm or more which was resected and reanastomosed to the anal canal. The resection was performed endoanally in three patients but was successful in only one. In the two patients in whom endoanal excision was unsuccessful and in the remaining three resection of at least 5 cm was performed transabdominally with endoanal reanastomosis. Three of these five patients were converted from catheterizing the reservoir to spontaneous evacuation, but two patients still needed to catheterize. All six patients benefited in terms of the need for, or frequency of, catheterization, or by improvement in continence. Excessive length of the efferent limb of an S ileal reservoir may cause unsatisfactory defaecation, which may be improved by partial resection. The transabdominal route is recommended for the resection, with endoanal reanastomosis. This surgery is potentially problematic and, although no anastomotic leakage was encountered, a covering loop ileostomy is recommended. PMID- 2317673 TI - Metabolism of body water and electrolytes after surgery for ulcerative colitis: conventional ileostomy versus J pouch. AB - Some authorities believe that patients with conventional ileostomies are chronically water and salt depleted but there are no data on the metabolism of body water and electrolytes after ileoanal J pouch. To clarify the situation we studied the body composition of 14 patients with well functioning ileostomies and 20 patients with well functioning J pouches. Both groups were compared with two closely matched control groups. Body weight, total body fat, fat-free mass, total body water and extracellular water were measured by neutron activation analysis, tritiated water and bromide dilution respectively; 24-h collections of urine and stool were analysed for volume and electrolyte content. The results show that the body content of water and extracellular fluid in ileostomy patients and J pouch patients is normal. The faecal volume and chemistry is similar in both groups resulting in a similar and significant degree of urinary sodium retention. PMID- 2317675 TI - Role of intraoperative prograde colonic lavage and a decompressive loop ileostomy in the management of transmural amoebic colitis. AB - A prospective analysis is presented of a selected group of 45 consecutive patients with transmural amoebic colitis treated by laparotomy, colonic lavage and ileostomy (phase 1 surgery) over 3 years. The diagnosis of amoebic colitis and amoebic perforation of the bowel were difficult and therefore all patients with 'acute abdomen' had proctosigmoidoscopy and a trial of metronidazole for 24 48 h before laparotomy. At laparotomy, adhesive wraps were present in all patients; 13 perforations were exposed by inadvertent disturbance of adhesive wraps but were successfully closed by suture to any available organ in close proximity, such as the omentum or small bowel. Four patients (9 per cent) died after phase 1 surgery. After 6 weeks when the acute disease had healed, 33 of the remaining 41 patients (80 per cent) required closure of ileostomy only, five had resection of stricture and three (7 per cent) needed stricturoplasty (phase 2 surgery). Two patients (5 per cent) died after phase 2 surgery. Thus, in surgery for transmural amoebic colitis adhesive wraps should not be disturbed as they mechanically protect the peritoneal cavity from faecal soiling when perforation occurs. The colon should be emptied by lavage and the faecal stream diverted to avoid secondary bacterial effects. PMID- 2317676 TI - Evaluation of the prognostic value of triple node biopsy in early breast cancer. AB - The prognostic information obtained by triple node biopsy (low axillary, apical axillary and internal mammary nodes) in 693 patients with early breast cancer has been reviewed. Results show that tumour site within the breast influenced which nodal groups were involved. The low axillary node contributed the most useful prognostic information. The involved apical node carried the worst prognosis. Either the internal mammary node or a low axillary node when positive alone carried the same prognostic weight. When both nodes were positive the prognosis declined to the level associated with apical node positivity. A double node biopsy of the low axillary node and either the apical or the internal mammary node gave the same maximum prognostic information as a triple node biopsy. The triple node biopsy technique can be used to divide patients into groups with vastly different prognoses. PMID- 2317677 TI - Intact parathyroid hormone in primary hyperparathyroidism. AB - In 49 patients with primary hyperparathyroidism, intact parathyroid hormone (PTH) was measured with a recently developed immunoradiometric assay, and midregional PTH fragments (sequence 44-68) were measured with an established radioimmunoassay technique. In 47 normal subjects, the concentration of intact PTH ranged from 2.0 to 6.8 pmol/l, and in 49 patients with primary hyperparathyroidism it ranged from 6.4 to 80.0 pmol/l. In contrast, midregional PTH fragments were normal in seven of 49 patients with primary hyperparathyroidism. In five healthy controls and in 12 patients with surgically confirmed primary hyperparathyroidism and serum calcium levels below 3.0 mmol/l, a rapid calcium loading test was performed. In healthy controls, intact PTH was in the low normal to subnormal range within 2.5 5.0 min, and had recovered within 15 min of calcium infusion. In patients with primary hyperparathyroidism, the calcium infusion also led to a 30-50 per cent decrease in intact PTH levels within 5.0-7.5 min after injection, with a slow recovery after 10-15 min. In six of the patients with only slightly elevated basal intact PTH, a suppression to the normal range was observed. In 24 patients (16 patients with a solitary adenoma and eight patients with four-gland hyperplasia) the intact PTH levels were followed intraoperatively during parathyroidectomy, revealing a significantly different rate of decline for single adenomas compared with hyperplasia during the first 15 min after removal of the primary enlarged gland. Intact PTH values remained constantly elevated in one patient with primary hyperparathyroidism and an unsuccessful neck exploration. These results confirm that (a) the measurement of intact PTH in patients with primary hyperparathyroidism is superior to the measurement of midregional fragments; (b) PTH secretion in primary hyperparathyroidism is not totally autonomous; and (c) intraoperative monitoring of intact PTH values could be used to monitor the success of surgery. PMID- 2317678 TI - Common femoral artery volume flow in peripheral vascular disease. AB - Common femoral artery volume flow was measured at rest and during postocclusive reactive hyperaemia in 80 normal subjects and 67 patients with radiological evidence of occlusive peripheral vascular disease. At rest, means(s.d.) common femoral artery volume flow in normal subjects (344(135) ml/min) and all patients with peripheral vascular disease (401(168) ml/min) was not significantly different. During postocclusive reactive hyperaemia, mean(s.d.) peak flow was significantly higher in normal subjects (1951(438) ml/min) than in patients with peripheral vascular disease (996(457) ml/min) (P less than 0.01). Common femoral artery volume flow in patients with critical ischaemia and intermittent claudication did not differ at rest but mean(s.d.) peak flow in patients with critical ischaemia (697(276) ml/min) was significantly lower than in claudicants (1131(447) ml/min) (P less than 0.01). Mean(s.d.) resting common femoral artery volume flow in limbs with femoropopliteal disease (457(185) ml/min) was significantly greater than that in limbs with occlusion of the aortoiliac segment (308(130) ml/min) (P less than 0.01). However, this difference did not persist during postocclusive reactive hyperaemia. A hyperaemic index, calculated from the hyperaemic responses to below knee and whole limb ischaemia, was used to quantify segmental perfusion during postocclusive reactive hyperaemia. The mean(s.d.) value in normal subjects, 46(9) per cent, and in those with aortoiliac disease, 52(12) per cent, indicated approximately equal perfusion of the above and below knee limb segments. In those with femoropopliteal disease the mean(s.d.) hyperaemic index was 17(13) per cent, revealing relative hypoperfusion of the below knee segment. PMID- 2317679 TI - Aortoiliac endarterectomy: an 11-year review. AB - Fifty-seven patients underwent aortoiliac endarterectomy over an 11-year period, the majority (86 per cent) for disabling claudication. No patient died within 30 days of surgery, but nine patients suffered significant complications. The cumulative survival rate was 98 per cent at 1 year, and was 94 and 78 per cent at 5 and 10 years respectively. Cumulative operated segment patency rates were 92 per cent at 5 years and 68 per cent at 10 years. There was no significant difference in survival rates between patients who smoked after surgery and those who did not, but smokers had significantly worse rates for cumulative patency, limb failure and symptom status than non-smokers. Twenty-seven patients developed worsening symptoms during follow-up and 24 patients required secondary vascular intervention. Fourteen patients subsequently required aortofemoral bypass and the largest single cause of operated segment failure was recurrent disease in the external iliac artery. Our evidence suggests that, while aortoiliac endarterectomy should be considered in young patients with localized disease not involving the external iliac artery, those who do not fit these criteria should be considered for primary aortofemoral bypass. Regardless of the choice of operation, the chance of success is jeopardized if the patient continues to smoke. PMID- 2317680 TI - Simultaneous aortic and renal artery reconstruction. AB - Nine patients presenting with combined aortic and renal artery disease underwent simultaneous infrarenal aortic reconstruction and renal revascularization. Seven patients had aneurysmal and two had occlusive aortic disease in association with unilateral (four cases) or bilateral (five cases) atheromatous renal artery stenosis. The indications for renal revascularization were hypertension (n = 8) refractory to medical treatment or associated with renal functional impairment and chronic renal failure alone (n = 1). Five patients developed postoperative complications with one fatality. Eight patients were followed up for between 7 months and 4 years. Control of blood pressure had improved in six of seven hypertensive patients. Serum creatinine levels were stabilized or had fallen in five patients. Simultaneous aortic and renal artery reconstruction is widely recognized as having a high postoperative morbidity rate but can improve control of hypertension and stabilize renal function in carefully selected patients. PMID- 2317681 TI - Effect of acute starvation on plasma fibronectin response to sepsis. AB - There is evidence that undernutrition may contribute to the reduction in plasma fibronectin concentration and the depression of the reticuloendothelial (RE) system associated with severe sepsis. We have investigated the effects of fasting, surgical trauma and sepsis on plasma fibronectin concentrations and RE function. In experiment 1, plasma fibronectin was measured in rabbits (n = 14) before and 48 h after fasting. In experiment 2, sepsis was induced by devascularization of the appendix in animals on a normal diet (sepsis group, n = 7). A third group of animals underwent only a laparotomy (laparotomy only group, n = 7). Plasma fibronectin concentrations and the blood clearance and organ distribution of 99mtechnetium tin colloid (TTC) were measured 24 h after operation. Compared with pooled reference plasma, fasting in experiment 1 resulted in a reduction in mean(s.e.m.) plasma fibronectin concentration from 98(1.5) per cent to 86(3.7) per cent (T = 2, P less than 0.005). Mean(s.e.m.) plasma fibronectin concentration was raised in the sepsis group to 117(4.6) per cent, compared with 97(2.5) per cent in the laparotomy only group (U = 5, P less than 0.02), but there was no such increase in the fasting and sepsis group. There was a delay in the blood clearance and reduced hepatic uptake of TTC in both sepsis groups. The dissociation between fibronectin concentrations and RE function in animal models of sepsis casts doubt on the importance of fibronectin in RE function. PMID- 2317683 TI - Electrically stimulated sartorius neosphincter: canine model of activation and skeletal muscle transformation. AB - The sartorius muscle was transposed into the abdominal cavity of six dogs, passed around a Thiry-Vella loop and sutured to itself to form a neosphincter. The muscle was activated by electrical stimulation and on contraction the neosphincter stopped or reduced the flow of saline through the Thiry-Vella loop in all animals until the onset of muscle fatigue. Continuous low frequency stimulation was used to transform the skeletal muscle, and when studied after a mean of 8 weeks of stimulation (range 6-11 weeks) the neosphincter stopped the flow for a significantly longer period of time (P = 0.027). Associated with the improved neosphincter function was a significant decrease in the fusion frequency (P = 0.003) and prolongation of the stimulus-peak tension time as assessed by a strain gauge sutured to the neosphincter muscle (P = 0.002). The changes in the contraction properties of the skeletal muscle suggest that continuous low frequency stimulation transformed the muscle fibres from type 2 to type 1, resulting in improved fatigue resistance and potential for continuous sphincter activity. PMID- 2317682 TI - Monocyte HLA-DR antigen expression characterizes clinical outcome in the trauma patient. AB - Immunological assessment is important to characterize the host defence response of trauma patients as infection is the most common cause of severe morbidity and late death. Sixty trauma patients were followed serially and divided into three groups: those with an uneventful recovery (n = 17), those with recovery after major sepsis (n = 27) and those who died (n = 16). The ability of peripheral blood monocytes to express the antigen HLA-DR was measured and compared to the results from 77 asymptomatic volunteers. After initial injury, there was a significant reduction from normal in the three trauma groups. It took one week for HLA-DR antigen expression to return to the normal range in the first group, three weeks in the second group, and in the third group it never returned to normal. Monocyte HLA-DR antigen expression, after incubation with lipopolysaccharide, distinguished those patients who survived from those who died. There was no difference in HLA-DR antigen expression between a high transfusion group of 31 patients who received 10 or more units of blood and a low transfusion group of 29 patients who received less than 10 units. The ability of monocytes to express HLA-DR antigen correlated directly with the clinical course in these patients and its measurement identified a group of patients at high risk of infection and death following trauma. PMID- 2317684 TI - Self protection in surgery: the use of double gloves. AB - This study assesses the perforation rate of single and double gloves and thus the extent to which double gloving protects the surgeon from diseases transmissible from the patient. We have also investigated whether double gloving offers the patient extra protection by reducing wound sepsis. Two hundred adult hernia repairs were performed, the first 100 single gloved and the second 100 double gloved. Glove perforation rates were not significantly different between single gloves and the outer of the double gloves. Although 46 of 400 outer gloves were perforated there were only 15 inner glove perforations and only eight of these matched the outer perforations. The percentage of operations in which the latex protective barrier was breached was reduced from 31 per cent when the surgeon wore single gloves to 8 per cent with double gloves. Wound sepsis was not increased by glove perforation nor reduced by double gloving. While careful technique remains mandatory we conclude that double gloving offers increased protection to the surgeon operating on high risk infectious cases. PMID- 2317685 TI - Pregnancy in a renal transplant recipient complicated by rupture of a transplant renal artery aneurysm. PMID- 2317686 TI - Cholecystokinin provocation test. PMID- 2317688 TI - Transanal resection of rectal tumours. PMID- 2317687 TI - Typhoid perforations. PMID- 2317689 TI - Nursing, teaching and computers--my experiences. PMID- 2317690 TI - Potential effects of decision support systems on the role of the nurse. AB - Decision support systems, and expert systems in particular, may have profound effects on nursing's role, causing the profession to reexamine the meaning of expertise for nursing and the educational strategies which enhance its development. In addition, expert systems provide support for enhanced scope of practice and greater autonomy, and they present intriguing liability challenges for the profession. Utilization of these sophisticated systems will encourage the trend toward increased information management, and will underscore the importance of nurses' interpersonal communication skills and their qualitative, ethical contributions to clinical decision-making. PMID- 2317691 TI - SNAP and dBASE. School of Nursing Admissions Program. AB - This article describes the use of dBASE software to facilitate computerized management of a school of nursing recruitment database. The School of Nursing Admissions Program (SNAP) provides an interface to commercial software to fit unique undergraduate and graduate program needs. By producing personalized computer-generated letters, SNAP enabled the school to increase its communication to prospective undergraduate and graduate students. PMID- 2317692 TI - Authoring systems. Finding the right tool for your courseware development project. AB - Many factors must be considered when selecting an appropriate tool for courseware development. An overview of development tools is provided. Based on the authors' experience in selecting an authoring system for a recent courseware development project, a practical process for selecting the appropriate tool is described. Considerations when determining the general needs for an authoring system and evaluating specific authoring systems' features are outlined. Selection considerations are also discussed. PMID- 2317693 TI - Psychiatric Nurses Association of Canada: a national education strategy for R.P.N.'s. PMID- 2317694 TI - Substance abuse in the elderly. PMID- 2317695 TI - Seasonal affective disorder. PMID- 2317696 TI - Let's have "ozone-friendly" pharmaceutical products. PMID- 2317697 TI - Has the CMA become "big business"? PMID- 2317698 TI - The CMA and abortion. PMID- 2317699 TI - Trends in use of medical services by the elderly in British Columbia. PMID- 2317700 TI - Third World aid. PMID- 2317702 TI - It is 25,000 operations and counting for Dr. Howard Gimbel. PMID- 2317701 TI - Naturopathic services. PMID- 2317703 TI - Transplantation of organs from newborns with anencephaly. Bioethics Committee, Canadian Paediatric Society. PMID- 2317704 TI - Basic Training Program in Medical Pedagogy: a 1-year program for medical faculty. AB - In 1979 universite de Montreal developed the Basic Training Program in Medical Pedagogy; the program has since been offered at two other Canadian medical schools. The learning activities are spread over an academic year so that the teachers are able to continue their clinical or research duties. The program, which follows a model of systematic instruction, comprises 17 self-instructional modules on basic educational topics adapted to medical teaching. The topics are related to four components of an integrated system: student needs and learning objectives, instructional methods, student evaluation and program evaluation. The instructional format is aimed at three levels--understanding, analysis and application--to which assignments and assessments are related. In addition to the modules, the program offers 15 half-day sessions for small groups (five participants and one instructor) to discuss aspects of the program, especially home assignments and the application of personal educational projects. A minimum of 100 hours of personal time is requested. The program's main goal is that students be placed at the centre of the educational process. Of 215 participants since 1979, 171 (80%) have completed the program and reported high satisfaction. Issues related to any faculty development program are discussed. PMID- 2317705 TI - Resuscitation from hypothermia-induced cardiac arrest. PMID- 2317706 TI - Claire and Tom and AIDS. PMID- 2317707 TI - The vulgarization of research. PMID- 2317709 TI - The patient-doctor relationship. PMID- 2317708 TI - CMA takes debate about health care south of the border. PMID- 2317710 TI - Physician advertising: The winds of change are blowing. PMID- 2317711 TI - Inhalant allergy to arthropods. PMID- 2317712 TI - Communicating clinical nurse specialist effectiveness. PMID- 2317713 TI - Gerontological nursing practice standards: achievement and importance. AB - The 1987 ANA Standards of Gerontological Nursing Practice is compared with the 1976 Standards and found to be a new document, not simply a revision. These 1987 standards are assessed using five queries: progression, timeliness, adequacy of scope, substance, and form. Eighteen nurses practicing at a long term care facility in the midwest rated both the achievement and importance of these new standards. Descriptive data analysis demonstrated unmet expectations for all but 1 of the 11 standards. One appropriate function of the gerontological clinical nurse specialist is ongoing evaluation of these nursing practice standards which will continue to describe and prescribe professional nursing practice. PMID- 2317714 TI - Measuring the difference between the means of two groups. PMID- 2317715 TI - Attributions about sexual experiences. AB - The findings of this study suggest areas for assessment and interventions that the clinical nurse specialist can use in counseling clients about sexual relationships. Emphasis in counseling should be placed on the mutuality of the sexual relationship and shared responsibility for both satisfying and unsatisfying experiences. PMID- 2317716 TI - Identifying major concerns of persons with acquired immunodeficiency syndrome: a replication. AB - A descriptive study was conducted at two major medical centers in Boston to identify and categorize major concerns of persons with acquired immunodeficiency syndrome. Thirty-four subjects were interviewed using a semistructured instrument, developed by Spross and her colleagues while at the National Institutes of Health. Obtained by referral from nurses caring for them in inpatient and outpatient settings, the majority of subjects were Caucasian, homosexual males from the Boston metropolitan area. The mean age of subjects was 33.6, with 71% less than 35 years old. Subjects reported an average of 3.2 hospitalizations since the AIDS diagnosis had been made; average time since diagnosis was 8 months. Information obtained from subjects included impact of diagnosis, major concerns and sources/types of support perceived to be helpful. Five themes were identified: uncertainty of the future; desire to maintain health; social unacceptability; fatigue; and weight loss. PMID- 2317717 TI - Managed care and the clinical nurse specialist. PMID- 2317718 TI - Strategies for practice as a clinical nurse specialist in a small setting. AB - The size of setting impacts the clinical nurse specialist's (CNS) practice in a myriad of ways. The many differences between small and large settings that affect the CNS role are identified, and the roles of clinician, educator, executive, and researcher illuminate facts and provide examples that demonstrate the limitations and benefits of a small setting. The three specialty areas represented include oncology, cardiovascular, and gerontology/community health. Practical strategies for practice of the clinical nurse specialist in a small or nontraditional setting are provided. PMID- 2317719 TI - A family systems nursing approach to premenstrual syndrome. AB - The paper presents a family systems nursing approach to premenstrual syndrome. The interaction between premenstrual syndrome and family dynamics becomes the focus for the clinical nurse specialist and her team. A case example illustrates the use of the interview guidelines of hypothesizing, circularity and neutrality and various systemic-strategic interventions. through this process the couple's maladaptive patterns of interaction are interrupted. Symptom prescription, symptom sharing, symptom escalation, and positive connotation are among the creative interventions used to release premenstrual syndrome from its triangulated position in the marriage. PMID- 2317720 TI - Perspectives on developing, marketing, and implementing a new clinical specialist position. AB - The purpose of this article is to provide guidelines for the clinical nurse specialist (CNS) who is involved in setting up a new position. The article describes the use of marketing strategies as a means of introducing the role to a prospective employer. Three guidelines are proposed as a framework for successful development of a new position. They are: (1) clearly defined purposes, goals, and role responsibilities, (2) mutual agreement of role expectations, and (3) self confidence of clinical knowledge and ability. The article discusses the issues of unrealistic expectations, credibility, and role competition as potential difficulties in implementing a new position and offers suggestions to assist the CNS to realize success in implementing a new position. The key to success in setting up a new position is to develop the function that makes the CNS most valuable to the employer. PMID- 2317722 TI - Clinical nurse specialist curriculum planning: a step toward development of a standard. PMID- 2317721 TI - Specialty nursing council: a peer support group for nurses in independent roles. AB - As nurses move into more nontraditional, expanded roles, they sometimes lack a social and professional support group within the work setting. Feeling isolated and lacking support, several clinical nurse specialists (CNSs) at a large county institution began the Specialty Nursing Council. The Specialty Nursing Council provides a means of networking and support for nurses in specialty roles in a three institution health care campus. Monthly meetings are conducted to bring members together and for continuing education programs. The keys to success in forming this type of council are: 1) a dedicated group that plans, organizes, and distributes informational material; 2) common goals and objectives; 3) direct benefits to members. PMID- 2317723 TI - Clinical issues in a nursing administration graduate program. AB - Should clinical nursing content be part of the preparation of future nurse executives? This issue has been debated by nursing administrators and nursing educators; many advocate some type of clinical knowledge base for nurse executives. In the graduate program in Nursing Administration at the State University of New York at Buffalo, we have developed a course that focuses on the administrative implications of current clinical issues. This course enables future nurse executives to explore clinical nursing problems and plan appropriate administrative strategies for confronting these problems. PMID- 2317724 TI - National agenda for elder care in America. PMID- 2317725 TI - Prevention of elder abuse: Betty Neuman health care systems approach. AB - It is estimated that as many as 2.5 million elderly persons in the United States every year are victims of abuse, neglected, battered, or otherwise deprived of their rights, usually by those on whom they are most dependent for care. Although there is no clear consensus on what constitutes or causes abuse, it is widely accepted that this national tragedy has growing implications for the future. Presented here are definitions of abuse, trends that have impact on the incidence of elder abuse, trends that have impact on the incidence of elder abuse and also theories of causation. In addition the Betty Neuman health care systems model is presented as a framework for the clinical nurse specialist to utilize in developing a plan of care aimed at preventing abuse while maintaining the integrity of the family. This framework and accompanying generalized plan of care could easily be adapted to other types of intrafamily violence. PMID- 2317726 TI - "Nursing is an art". PMID- 2317727 TI - Neuroleptic malignant syndrome. PMID- 2317728 TI - The brain and the mind. PMID- 2317729 TI - Treatment focus in psychiatry. PMID- 2317730 TI - Propranolol in the treatment of postencephalitic psychosis. PMID- 2317731 TI - Effect of concurrent medical illness on dexamethasone suppression test results in depressed inpatients. AB - A retrospective evaluation of the clinical records of 138 depressed patients, who received the dexamethasone suppression test (DST) as part of a standardized physical and psychiatric assessment protocol, revealed that 60 had acute, chronic (mild or severe), stable or remitted medical conditions. The proportion of DST nonsuppressors did not differ between depressed subjects with medical conditions (45% nonsuppressors) and those without (34.6% nonsuppressors; p greater than 0.2). However, all of the six subjects with acute or chronic-severe medical conditions were found to be nonsuppressors (p = 0.003). These results may help clarify the medical exclusion criteria for the clinical application of the DST. PMID- 2317732 TI - The remitting atypical psychoses: clinical and nosologic considerations. AB - There exists in the literature a group of nonorganic psychoses which appear to have no obvious relationship to either schizophrenia or affective illness. Diagnostic terminology to classify these atypical psychoses has been varied, although features in common can be identified. For example, they often are associated with antecedent personality problems, acute onset, florid and mixed symptomatology, brief duration, and full remission with a return to premorbid level of functioning. Case material reflecting these types of psychoses is presented here, and is discussed with reference to the nosologic status of these atypical psychoses. PMID- 2317733 TI - An examination of Mann's model of time-limited individual psychotherapy. AB - The present study attempted a sensitive test of the dynamic sequence proposed by Mann for time-limited individual psychotherapy (TLP). Session evaluation ratings were collected from both patient and therapist. Indices were constructed that reflected the consistency of patient ratings, the consistency of therapist ratings, and the congruence between patient and therapist ratings, in each third of TLP. Measures of symptoms and social functioning were employed to differentiate cases of "good" versus "poor" treatment outcome. Therapists' adherence to the TLP technique was assessed by categorizing all interventions in each session. Fourteen patients were treated according to the TLP model. Measures of therapist behaviour indicated that treatments had been conducted in general accordance with Mann's technical recommendations. Measures of consistency and congruence failed to support the proposed TLP dynamic sequence. Analyses of mean evaluation ratings indicated a trend towards more positive evaluations as therapy progressed; "good" outcome cases were significantly more likely to evidence this pattern. Results are discussed in terms of interplay between inductive hypothesis building and empirical verification in the development of theories of psychotherapy. PMID- 2317734 TI - The etiology of nonpsychotic emotional illness. AB - Two hundred and fifty couples in the general population completed self-report questionnaires which measured life events, personality, marital intimacy, and symptoms of nonpsychotic emotional illness. Path analysis was utilized to explain the development of symptoms of nonpsychotic emotional illness. Personality traits of neuroticism and extroversion explained most of the variance of symptoms of nonpsychotic emotional illness. Life events played a much smaller but significant role and marital intimacy was a nonsignificant factor. The data support a proneness model for the etiology of nonpsychotic emotional illness. PMID- 2317735 TI - An integrated approach to family therapy training for psychiatric residents. AB - Unlike nonmedical family therapists, psychiatric family therapists are able to evaluate and treat both the biological and psychosocial components of a problem. They can integrate knowledge of biology, psychopharmacology and individual psychodynamics with family systems theory and family therapy skills. A family therapy training program is presented as a model which prepares psychiatric residents for this unique role. This model emphasizes the importance of having psychiatrists as family therapy teachers, the use of both systems and psychodynamic perspectives in teaching about families, and the principle of presenting concepts and interventive techniques at successively greater levels of difficulty. Illustrative examples are presented. A minimum of two years of family therapy training and supervision is recommended during a four year residency program. PMID- 2317736 TI - [Formal thinking, logical-discursive operations and schizophrenia: experimental study of a clinical case]. AB - This study, based on a single case experimental design, examined logical reasoning in a schizophrenic meeting the DSM-III criteria. The quantitative assessment carried out by 32 psychiatrists on a rating scale for logical thinking disorders (nine items, six points) of the retranscribed clinical interview showed 1. that the assessments varied in a statistically significant way according to items and psychiatrists, and that these variations were independent of their degree of experience--the correlations between the different items of the rating scale proved to be weak and not significantly different from zero; and 2. the study of the most contradictory statements carried out by a logician using reasoning analysis procedures concluded that there were in fact logical relationships between the subjects the schizophrenic talked about. The results are discussed in relation to the methodology of assessing formal thought in schizophrenia. PMID- 2317737 TI - Some factors relating to satisfactory post-discharge community maintenance of chronic psychotic patients. AB - The length of time a group of 70 psychiatric patients could be maintained in the community following discharge from a provincial hospital was found to be significantly related to post-discharge compliance with medication and to the level of discharge planning (well planned versus unplanned, or patient prematurely self-discharged against medical advice). Various demographic and clinical variables were unrelated to the length of post-discharge survival in the community. PMID- 2317738 TI - A brief note on serum calcium levels in schizophrenics and controls. AB - The present investigation examined the relationship between serum calcium levels and schizophrenic disorder. Unlike earlier studies a wider range of diagnoses was surveyed, subjects were limited to first time admission, and the relationship of socio-demographic factors to the hypothesized biological risk factor was assessed. Analysis revealed no significant differences in levels of serum calcium between schizophrenics and four nonschizophrenic comparison groups, nor were any one of several socio-demographic factors found to correlate significantly with serum values. Some risk factors, however, differentiated between schizophrenics and nonschizophrenics. They were being single, poor employment history, and reason for admission. A more promising avenue for further research in the area is outlined. PMID- 2317739 TI - The impact of the amended Ontario Mental Health Act (Bill 7) on patients discharging themselves from hospital against medical advice (AMA): a preliminary study. AB - Bill 7, the most recent amendment to the Ontario Mental Health Act was introduced in December 1986. It has resulted in some major changes to the practice of psychiatry, especially in provincial hospitals. We compared patients who had discharged themselves against medical advice (AMA) during the six months before the Bill was enacted, with those who discharged themselves AMA in the 12 months following. Significantly more patients discharged themselves AMA in the post- than the pre-Bill period. The majority of these were potentially treatable, acutely ill individuals with schizophrenia or affective disorder. We argue that Bill 7 has largely failed in its objective to improve the overall "quality of care" to psychiatric patients, at least in the short term. PMID- 2317740 TI - A case study: schizophrenia and tactile hallucinations, treated with electroconvulsive therapy. AB - The authors review the literature on tactile hallucinations. They examine its occurrence in a schizophrenic patient who had poor response to neuroleptic medication, after several admissions to a psychiatric hospital. The patient responded well to electroconvulsive therapy when it was combined with a small dose of a neuroleptic. Due to prolonged use of neuroleptics he developed tardive dyskinesia that responded only to a large dose of lecithin. They discuss the use of electroconvulsive therapy in schizophrenic patients who have shown little or no response to neuroleptics after prolonged use. The case presented showed better clinical response with smaller doses of antipsychotic medication, when combined with electroconvulsive therapy. PMID- 2317741 TI - [Contemporary aspects of psychiatry in Communist China]. AB - Psychiatry in Communist China is at a delicate phase where it is drawn both to modern Western medicine and to the wealth of traditional medicine. This is conveyed through accounts of some present-day situations as seen by the author during stays in Peking and Shanghai. After the treatment provided in various hospitals for acute-care and chronic-care patients is described, we are introduced to the organization of mental health at the various levels of hospital and external structures. A general survey of the research being done in epidemiology, neurology and traditional medicine at the Peking Research Centre is also presented. The novel nosography reveals one particular entity: phasophrenia, described as a stereotyped and recurring acute psychotic episode that responds poorly to neuroleptic chemotherapy. Finally, the medico-legal aspects of psychiatry and the effects of the new birth-rate policy are briefly discussed. PMID- 2317742 TI - Women as torture victims. AB - This paper reports a retrospective study of the frequency, severity, modalities and mental health consequences of torture in 28 Latin American refugee women in Toronto. The data on these women and a comparison group of male torture victims were retrieved from case records in a hospital outpatient clinic. The results support the hypotheses implicit in the scanty literature available that the frequency and effects of torture in women differ from those found in men. In female victims, as in their male counterparts, the severity of the torture was related to the degree of their political involvement. However, torture was more frequently sexual, and its consequences more often affected the women's sexual adaptation. PMID- 2317743 TI - Children who survived Japanese concentration camps: clinical observations and therapy. AB - The majority of children who survived concentration camps have remained silent about their experiences. Their memories, rather than fading with time, have intensified. In the 1970s previously silent Jewish child survivors declared themselves through books and films. Child survivors of Dutch origin who were the victims of Japanese concentration camps are similarly emerging from silence. Parents and even psychiatrists do not credit child survivors with their ability to remember. As a result, child survivors have difficulty verifying their memories and have spoken very little about them. The numbers of patients with this particular childhood experience are increasing as noted in Dutch clinics devoted to the care of victims of war. This paper focuses on two such patients in order to alert North American psychiatrists to their existence and to crucial aspects of their care. PMID- 2317744 TI - Separation experiences in childhood and adult marital quality. AB - A relational model of the influence of childhood relationships on adult marital quality is proposed and tested in a family medical centre and a psychiatric outpatient population by a questionnaire of separation experiences, the Parental Bonding Instrument and the Locke-Wallace Short Marital Adjustment Test. This paper presents results from a psychiatric outpatient population that correspond with previously reported results on the family medical centre patients. The paper also presents data from both populations on the association of childhood separation experiences with adult marital quality. The presence or absence of self-reported childhood separation experiences was not associated with variations of marital quality in either population. The variation in other aspects of separation experiences similarly was not associated with marital quality. The association between representations of childhood experience and adult marital quality, found in a previous study of the family medical centre patients, was not found in the psychiatric outpatient population. The possible reasons for these findings are discussed. PMID- 2317745 TI - Psychological factors in irritable bowel syndrome. AB - This paper describes the prevalence and incidence of psychiatric disorders in IBS patients using a standardized psychiatric interview, and proposes a psychological model for investigating one aspect of IBS. Forty-four IBS patients and 28 nonclinical participants received a psychiatric interview (Diagnostic Interview Schedule) and completed the Lie Scale of the Eysenck Personality Inventory (L EPI). Results indicated that a significant percentage (59%) of the IBS group met DSM-III criteria for a psychiatric disorder within the last year, far more than occurred in the matched nonclinical comparison group. Relative to the comparison group, the IBS group also had significantly higher lie scores on the EPI indicating a response style of social desirability. On the basis of these findings, together with earlier work by Latimer's group, a conceptual model was formulated on the notion that some IBS patients may have a self-schema (i.e. knowledge of self, stored in memory) characterized by social desirability. We suggest that the construct of self-schema may be helpful in differentiating IBS from psychiatric groups both conceptually and therapeutically. PMID- 2317746 TI - Canadian projections of cases suffering from Alzheimer's disease and senile dementia of Alzheimer type over the period 1986-2031. AB - Alzheimer's disease (AD) is characterized by irreversible changes in cognitive and intellectual functions, accompanied by progressive memory loss, and described by neurochemical and neuropathological impairments. The classic term Alzheimer's disease applies to presenile dementia, while all of the syndromes that share the distinctive signs of AD are known as senile dementia of the Alzheimer type (SDAT). In Canada, as in several other industrialized countries, we are seeing a rapid growth of the elderly population. The renewed interest in AD and SDAT is partly attributable to the view that the increasing percentage of sufferers will have a significant socioeconomic impact. Few attempts have been made to project the number of cases of SDAT in Canada. In assessing the prevalence of SDAT in an over 65 population, a rate of 2.5% (or 3%) is commonly applied. This rate corresponds to one half the estimated prevalence rate for all severe types of dementia, using an average of the rates arrived at by some ten studies. The authors dispute this approach: i. the assumption that 50% of dementia cases will be AD is not verified for all populations; ii. the use of a single prevalence rate for everyone over age 65 is rather uninformative; and iii. the combining of results from various sources is questionable given the possible lack of consistency in the following respects: diagnostic criteria, methods of investigation, effort made to recruit cases, and representativeness of the groups studied. In this article, prevalence rates by age group have been inferred based on two Finnish studies conducted in the 1980s on the prevalence of AD in the general population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317747 TI - The criminalization of the mentally ill. AB - This paper presents three patients with manifest psychotic illnesses who were directed into the legal system when they committed criminal acts. All of the patients were ordered to attend a psychiatrist for the year they waited for trial. All three patients pleaded guilty; two were put on probation with continuing psychiatric attendance, a condition of probation, and the other was given an absolute discharge when the court was assured that the patient would remain in treatment. Two of the patients who had previously been noncompliant with psychiatric treatment became very compliant and cooperative as a result of the court process and probation order. The third patient was compliant and cooperative both before and after the legal proceedings. All three patients were embarrassed by the criminal charges and disliked the legal process. Since civil commitment laws have changed, psychiatrists must not abandon the seriously mentally ill but should be willing to treat patients backed up by a probation order. The cooperation of medical and legal professionals is in the patients' interest. PMID- 2317748 TI - [Depression with panic attacks: clinical characteristics and prevalence in hospital]. AB - Seventy-three patients successively hospitalized in psychiatry and meeting the criteria of the DSM-III for diagnoses of major depressive episode with or without melancholia (n = 64), dysthymia (n = 5) or adjustment disorder with depressed mood (n = 2) were studied. Of these 73 patients, 50.7% also exhibited, at the time of their hospitalization, panic disorder as defined by the DSM-III criteria (53.4% having exhibited this disorder at some time in their life). Moreover, eight of the 73 patients (11%) exhibited, or had exhibited at some time in their life, a "sub-panic" state characterized by recurring rudimentary attacks, while five of the 73 patients (6.8%) exhibited "permanent panic anxiety" tending to fluctuation rather than paroxysm. These two forms of anxiety raise the question of the limits of panic disorder. The comparison of depressions with and without panic disorder shows an even distribution of endogenous and nonendogenous forms in both groups. Depressions with panic disorder, moreover, registered greater intensity (according to the HDRS score), a higher lever of anxiety (according to the AMDP-AT score), and a higher degree of nervousness (according to the EPI score) than depressions without panic disorder. The study of the chronology of the associations between depressions and panic disorder shows that in more than one-half of the cases these disorders began within one month of each other. In one-third of the cases, panic disorder preceded the depressive episode by more than one month. And finally, in just over 10% of the cases, panic disorder appeared more than one month after the beginning of the depressive episode. PMID- 2317749 TI - Multiple personality disorders. PMID- 2317750 TI - Psychiatry and chronic pain. PMID- 2317751 TI - Simultaneous versus sequential combined technique therapy for squamous cell head and neck cancer. AB - Forty-eight patients with locally confined (M0) squamous cell head and neck cancer were prospectively randomized to receive either simultaneous (SIM) or sequential (SEQ) combined technique therapy with a 5-fluorouracil infusion, a cisplatin bolus injection, and radiation therapy. Patients with residual resectable disease underwent surgery after induction therapy, whereas those achieving a complete response to induction did not require surgery. Patients on the two treatment arms were equivalent in all measured variables, including disease extent. Toxicities of the SIM and SEQ arms also were equivalent except for mucositis and the resultant weight loss, which were more severe on the SIM arm (P = 0.002). With a follow-up time ranging from 9 to 41 months, seven of the 24 SIM patients and 14 of the 24 SEQ patients are considered treatment failures. The relapse-free survival is significantly better on the SIM arm (P = 0.03), although an overall survival advantage has not yet been demonstrated (P = 0.13). The achievement of a complete response after induction therapy correlates with both the relapse-free (P = 0.0005) and overall (P = 0.05) survival, and the likelihood of an induction complete response also is significantly better for those treated with the SIM schedule (P = 0.02). Eighteen patients did not require surgery after achieving an induction complete response. Relapse-free survival does not appear to be compromised in this patient subset. PMID- 2317752 TI - Continuous cyclophosphamide, doxorubicin, vincristine, and prednisolone. A new, innovative protocol for diffuse aggressive lymphomas. AB - One hundred eight patients with aggressive non-Hodgkin's lymphoma (high and intermediate grade) were treated with a new protocol: continuous cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). They were evaluated for long-term survival and pretreatment characteristics predictive of response and survival. Continuous CHOP protocol consists of initial 8 weeks of intensive chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, followed by local/cranial radiotherapy and maintenance therapy. Complete remission (CR) was achieved in 84 of 108 (78%) patients; seven (6%) had a moderate response and 17 (16%) had a poor response. A statistically significant difference in CR rate was found only in patients with different stages. Seventeen of 84 (20%) complete responders have had a relapse of the disease. The median survival has not been reached. Results show an actuarial disease-free survival (DFS) of 77% for the 84 patients who had a complete response. The overall survival for all patients was 53% at 5 years of follow-up. The difference in DFS at the end of 5 years between different stages, main histologic subgroups, and age groups was not statistically significant. The toxicity observed was acceptable. Thus continuous CHOP appears to be an effective protocol for the treatment of intermediate-grade and high-grade lymphomas. PMID- 2317753 TI - Platelets acquire a secretion defect after high-dose chemotherapy. AB - Patients receiving high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) may experience life-threatening hemorrhagic myocarditis. The authors investigated whether HDC was associated with an acquired platelet defect. Platelet aggregation and release were evaluated after HDC in ten patients with either metastatic breast carcinoma or melanoma. Platelets underwent shape change and a primary wave of aggregation. High-dose chemotherapy was associated with the inhibition of secondary aggregation of platelets induced by adenosine diphosphate (ADP), arachidonic acid, prostaglandin H2 (PGH2) analog (U44619), and collagen. Although electron microscopic study of the platelets revealed normal morphologic features with an adequate number of dense bodies and alpha-granules, release of adenosine triphosphate (ATP) from dense granules was less than 20% of normal. The acquired platelet defect occurred before development of thrombocytopenia. Aggregation of platelets from normal volunteers was not inhibited by either the addition of the chemotherapeutic agents, chemotherapy metabolites, or the patients' sera. In conclusion, HDC induces an acquired abnormality in platelet secretion and aggregation which may contribute to the development of hemorrhagic complications after ABMT. PMID- 2317754 TI - Osteonecrosis in pediatric patients with acute lymphoblastic leukemia. AB - The authors report five pediatric patients with acute lymphoblastic leukemia (ALL) in whom symptomatic aseptic osteonecrosis developed on therapy. All patients had been on treatment with a modified BFM protocol and developed osteonecrosis in the maintenance phase of the protocol. The avascular necrosis was multifocal in all. The authors' data suggest that dexamethasone used in the reinduction phase of the protocol may be the responsible agent although no definite proof exists. Since only symptomatic patients are reported, the true frequency of this complication may be significantly higher. PMID- 2317755 TI - Fluorescence microscopic demonstration and demarcation of doxorubicin extravasation. Experimental and clinical studies. AB - Extravasation of doxorubicin and its derivative epirubicin, cause severe progressive tissue necrosis that requires early excision of all affected tissues. Doxorubicin and epirubicin are autofluorescent and this characteristic can be used to demonstrate and delineate extravasation by the aid of fluorescence microscopic study. In a rat model doxorubicin was injected intradermally in declining concentrations and the minimal detectable concentration was found to be 0.02 mg/ml. Skin necrosis developed in rats injected with doxorubicin concentrations ranging from 0.02 mg/ml to 2 mg/ml. Clinically, fluorescence microscopic analysis of frozen sections was used in eight patients to assess whether doxorubicin or epirubicin extravasation had taken place. When all fluorescing tissue was removed, no necrosis ensued, but in one patient, where a slightly fluorescing area was ignored, necrosis developed later and excision of the tissue had to be performed. PMID- 2317756 TI - Is there no influence of local control on the rate of metastases in high-grade soft tissue sarcoma? AB - Primary host and tumor-related prognostic factors, the occurrence of local recurrence, and the time interval between diagnosis of the primary tumor and metastatic disease were analysed in 39 patients with metastatic Grade 4 soft tissue sarcoma. The pattern of prognostic factors and the timing of metastases were the same in patients with and without local recurrence. Thus, primary prognostic factors alone may determine the risk of metastases in high-grade soft tissue sarcoma; local recurrence per se may not influence the prognosis in these cases. PMID- 2317757 TI - Tumor cells in intraoperative pleural lavage. An indicator for the poor prognosis of bronchogenic carcinoma. AB - Fifty-nine patients with bronchogenic carcinoma and 21 patients with nonneoplastic lung diseases underwent intraoperative pleural lavage with 300-ml physiologic saline before (Lavage I) and after resection (Lavage II). The presence of tumor cells in the lavage fluid was established cytologically in 29 patients with bronchogenic carcinoma. Twenty-seven had positive findings in Lavage I and 23 of these also in Lavage II. Two patients had positive findings in Lavage II only. All controls were negative. In all 40% of patients with Stage I bronchogenic carcinoma had positive lavage results. The cumulative two-year survival rate of this group is 40%, which differs significantly (P less than 0.01) from the 97% survival rate of the patients with the same tumor stage whose lavage findings were negative. Detection of tumor cells in pleural cavity washings before resection proves that tumor cells have spread into the pleural cavity. Cytologic examination of an intraoperative pleural lavage should be done when assessing the tumor stage. PMID- 2317758 TI - Prognostic significance of intramural metastasis in patients with esophageal carcinoma. AB - Clinicopathologic data on 201 patients who underwent surgical resection of esophageal squamous cell carcinoma, with or without intramural metastasis (IM), were analyzed to determine the significance of IM for patient prognosis and survival. In 24 (11.9%) patients IM was observed. There was one (1.4%) in 74 cases in Stage 0, I, or II, and 23 (18.1%) in 127 cases in Stage III or IV, based on the new pTNM classification. There was a statistically significant Cox-Mantel test difference in the percentage survival curves of the patients, both in all stages (P less than 0.01) and in only Stages III and IV (P less than 0.05), as a function of the presence or absence of IM. Lymph node metastasis and distant organ metastasis were observed in 22 (91.7%) and seven (29.2%) of the 24 patients, respectively, with IM and in 111 (62.7%) and 13 (7.3%) of the 177 patients without IM. For both types of metastasis, the incidence was significantly lower in the patients without IM (P less than 0.01). Seventy percent of IM on the proximal side was detected during preoperative clinical examination. These data indicate that the presence of IM is an important factor for preoperative and postoperative evaluation of the prognosis of patients with esophageal squamous cell carcinoma. PMID- 2317759 TI - Tissue carcinoembryonic antigen and DNA aneuploidy in precancerous and cancerous colorectal lesions. AB - Chronic inflammatory bowel disease (CIBD) and colorectal adenoma are considered as precancerous conditions and lesions of large bowel carcinoma, respectively. They, therefore, may be used to study the behavior of such different factors as tumor-associated antigens and nuclear DNA content abnormalities in colorectal carcinogenesis. Tissue concentrations of carcinoembryonic antigen (CEA) were significantly higher in those precancerous lesions (CIBD: 61 +/- 11.2 ng/mg, adenoma: 70 +/- 6 ng/mg; mean +/- standard error of the mean) than in normal colonic mucosa (36 +/- 4.7 ng/mg). Colorectal carcinoma had still higher tissue levels (437 +/- 108.2 ng/mg). No correlation between tissue CEA and tumor differentiation could be found, but there was a significant difference between aneuploid (747 +/- 354 ng/mg) and diploid (139 +/- 43 ng/mg) tumors. Using flow cytometry DNA aneuploidy was present in 31.6%, 10.5%, and 51.6% of CIBD, colorectal adenoma, and carcinoma, respectively. These data suggest that the occurrence of aneuploidy is not strongly dependent on a malignant transformation, but it may also be present in premalignant colorectal lesions without cellular dysplasia. PMID- 2317760 TI - Diploid predominance in hereditary nonpolyposis colorectal carcinoma evaluated by flow cytometry. AB - Fifty-nine colorectal carcinomas of patients with verified cancer family syndrome (CFS) were analyzed for DNA ploidy using flow cytometry. Sixty-eight percent of the tumors were diploid, and 32% were aneuploid. The aneuploid tumors had a median DNA index of 1.24 (range, 1.12-1.97). In 90% of all tumors the DNA index was less than 1.27. This predominance of diploid/near-diploid tumors was seen both in primary and in metachronous carcinomas. In 21 cases a cell cycle analysis was possible. Tumors with the S-phase fraction (SPF) greater than or equal to 9.8% had a worse prognosis than tumors with the SPF of less than 9.8%. These findings suggest that the predominance of diploid/near diploid DNA values is one of the characteristics of colorectal carcinomas in CFS. This might signify the existence of two or more pathogenetically different subgroups of colorectal carcinoma and explain the proposed better prognosis of colorectal carcinoma in CFS compared with other colorectal carcinomas. PMID- 2317761 TI - Adenocarcinoma of the uterine cervix. Prognostic significance of pretreatment serum CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen levels in relation to clinical and histopathologic tumor characteristics. AB - The prognostic value of the pretreatment serum CA 125, squamous cell carcinoma antigen (SCC), and carcinoembryonic antigen (CEA) levels in relation to tumor type, vascular invasion by tumor cells, and lymph node metastases was investigated in 77 patients with cervical adenocarcinoma. In Stage IB (International Federation of Gynecology and Obstetrics [FIGO]), the five-year actuarial survival of patients with pretreatment serum CA 125 levels greater than 16 U/ml was 52.4% versus 95.6% when normal serum CA 125 levels were determined (P less than 0.01). Pretreatment serum SCC or CEA levels had no substantial prognostic value. In Stage IB (FIGO), 42% of the patients with elevated serum CA 125 levels had lymph node metastases versus 4% when normal levels were found (P = 0.012). The presence of vascular invasion (P = 0.01) or lymph node metastases (P = 0.001) was associated with an increased risk for recurrent disease. Adenosquamous tumors showed a higher incidence of vascular invasion (P = 0.05) and a higher incidence of elevated serum CA 125 levels (P = 0.03). Particularly in Stage II, adenosquamous tumors were found to have a poorer prognosis than adenocarcinomas (P = 0.0566). We conclude that in cervical adenocarcinoma serum CA 125 is an important prognostic factor and an implicit indicator of tumor virulence. PMID- 2317762 TI - Malignant giant cell tumor associated with leiomyosarcoma of the uterus. AB - A unique association of uterine malignant giant cell tumor (MGCT) with leiomyosarcoma (LMS) is described. Contrary to the true mixed sarcomas, they appeared as two adjacent tumors with distinctly different gross, histologic, ultrastructural, and immunohistochemical features and little intermixing at their border. The dissemination of MGCT resulted in the fatal outcome 81 days after hysterectomy. Malignant giant cell tumor and LMS were coexistent neoplasms, which derived probably from different progenitor cells. It is suggested that MGCT could develop in association with preexisting LMS. PMID- 2317763 TI - Two different lymph node metastatic patterns of a prostatic cancer. AB - Among 753 autopsy prostatic cancer cases with a metastasis, 476 (63%) had a lymph node metastasis, whereas 277 (37%) did not. Two different lymph node metastatic patterns were observed: Type 1, combined metastasis involving the pelvic and paraaortic lymph nodes; and Type 2, metastasis to the paraaortic lymph nodes, but not to the pelvic lymph nodes. Type 1 metastasis cases showed a significantly more frequent metastasis to the bladder and rectum, and a less frequent metastasis to the lungs and liver. Hydronephrosis occurred more frequently (P less than 0.01) in the Type 1. Furthermore, in the Type 1 cases the lymph node metastasis appeared to be continuously invasive, but in the Type 2 cases, metastasis appeared to be the skip type or some metastases may have spread via the vertebral vein bypass route and may have been associated with a hematogenous metastasis. PMID- 2317764 TI - Fine needle aspiration cytology of chondroblastoma of bone. AB - Between 1979 and 1987 12 patients with chondroblastoma underwent fine needle aspiration (FNA). There were eight female and four male patients (age range, 11 35 years) with lesions of the proximal humerus (three cases), distal femur (two cases), proximal tibia (two cases), proximal femur, distal tibia, talus, navicular bone, and fifth metacarpal (one case each). The radiologic features of the tumors were not entirely typical of chondroblastoma in the majority of patients. The aspirate was diagnosed as chondroblastoma in seven cases, was considered strongly suggestive of chondroblastoma in one case, was found to be diagnosable as chondroblastoma on review in one case, and was nondiagnostic in two cases. The remaining case, which showed giant cell tumor-like areas in addition to typical chondroblastoma on histologic sections from the curettage, was interpreted as giant cell tumor on FNA. There was no case in which an aspirate was erroneously diagnosed as chondroblastoma. On FNA, chondroblastoma had three dominant cytologic components: neoplastic mononuclear cells (chondroblasts), multinucleated osteoclast-like giant cells, and chondroid matrix fragments. The chondroblasts tended to lie individually in smears creating a pebbled appearance. They most commonly had round to oval nuclei with fine, evenly distributed chromatin and distinct longitudinal grooves, but indented, lobulated, and pyknotic nuclei were also observed. Their cytoplasm was dense and opaque with rounded well-defined borders. Multinucleated osteoclast-like giant cells were randomly admixed and were indistinguishable from those seen in other bone neoplasms. Chondroid matrix stained magenta with the Diff-Quik stain and green to violet with Papanicolaou. The cytologic features of the chondroblasts are the diagnostic hallmark of chondroblastoma and may allow FNA to become a valuable preoperative technique in the management of these patients. PMID- 2317765 TI - Performance status assessment in cancer patients. AB - Performance status assessment, Karnofsky performance status (KPS), and Eastern Cooperative Oncology Group (ECOG) scales were performed in 100 consecutive patients independently by two physicians and by the patients themselves to evaluate the scales' validity and reliability. Findings of Kendall's correlation were highly significant between physicians (0.76 for KPS, 0.75 for ECOG) and between physicians and patients (0.65 for KPS, 0.59 for ECOG). The authors point out that patients' self evaluation could provide a valuable and reliable assessment. PMID- 2317766 TI - Chromosome analysis of cryopreserved cells. AB - We describe a technique for freezing and thawing human leukemic cells for cytogenetic studies. We studied 64 harvests on 26 cryopreserved samples from 20 individuals. Chromosome quality was best in the samples from patients with myeloid disturbances. Successful chromosome studies of approximately 50% of the samples were accomplished. Cryopreservation of leukemic cells is not a substitute for fresh material because the method produces relatively few metaphases and mediocre chromosome spreading and banding. However, when rigid and appropriate research objectives are applied, chromosome analysis of cryopreserved leukemic cells can be a viable alternative to analysis of fresh cells. PMID- 2317767 TI - Acquired Robertsonian translocations in hematologic malignancy. A rare mechanism of clonal evolution. AB - We identified three patients with an acquired Robertsonian translocation among 1,200 patients with hematopoietic malignancy. In each case the translocation served to produce partial chromosomal trisomy or tetrasomy within the malignant clone. Acquired Robertsonian translocation represents another, although rare, mechanism of clonal evolution in malignant cells. PMID- 2317768 TI - Chromosomal changes in renal cell carcinoma. No evidence for correlation with clinical stage. AB - A cytogenetic study was performed in 18 renal cell carcinomas using a culture method previously described. The significance of chromosome involvement in clonal aberrations was evaluated according to the mean + 1 SD objective criterion. Chromosomes 3, 7, 9, and 17 were preferentially involved in both numerical and structural changes. The cytogenetic data have been correlated with the clinical staging, but in contrast to a previous study, abnormalities of chromosome 3 were not associated with a higher clinical stage. PMID- 2317769 TI - Chromosome mapping using polymerase chain reaction on somatic cell hybrids. AB - DNA polymerase chain reaction (PCR) was used to detect specific human sequences in human-mouse somatic hybrids. As compared with classic Southern blotting, this technique appeared to be more sensitive and less time-consuming for gene mapping. PMID- 2317770 TI - Involvement of 9p in metastatic ovarian adenocarcinomas. AB - By a direct method and after in vitro culture, we cytogenetically analyzed five ovarian adenocarcinomas, using six samples of ascitic fluid. The structural aberrations included rearrangements of chromosomes 1 and 3, in agreement with the results of other researchers. The long arm of chromosome 6 was rearranged in three samples, but no translocation t(6;14) was found. Rearrangements involving 9p were present in all cases, with breakpoints at p13 or p22-23. PMID- 2317771 TI - Cytogenetic follow-up in a case of Sezary syndrome. AB - A cytogenetic follow-up study was performed for a 3-year period on a 70-year-old patient with Sezary syndrome (SS). The results showed formation of hypotetraploid cell clones with 60 to 89 chromosomes and 19 markers, some of which appeared during the period of study and stabilized thereafter. The incidence of these clonal cells increased from 29% to 85% during the follow-up study. The results confirm the presence of hypotetraploid cell clones, especially in the more advanced stages of SS. Moreover, some marker chromosomes in our patient (M2 and M3), derived from chromosome 2, were similar to those observed in SS by other investigators. According to our data and to those in the literature, SS appears to involve preferentially chromosomal regions 2p12-13, 2p21-22, 2q37, 17p13, 13q1, 9q11, 10p13, 14q11, 14q32, 7p1 and, to a lesser extent, 5q and 6q. PMID- 2317772 TI - Correlation between cytogenetic and histopathological findings in 65 human meningiomas. AB - The correlations between cytogenetic and histopathological findings were analyzed in 65 cases of human meningiomas. Clonal chromosome abnormalities were present in 28 cases (43%). The overall female/male ratio was 1.7, but it was 1.1 in the group of 28 cases with chromosomal abnormalities. Abnormalities of chromosome 22 as sole abnormality predominate in the female patients. The mean age of patients with normal karyotype was significantly lower (50.7 years) than that of patients with chromosome changes (57.3 years). The tumor origin was predominantly at the base in the patients with normal karyotype but different at the convexity, falx cerebri, and spinal cord. The five abnormal cases from the spinal cord all showed involvement of chromosome 22. The proportion of chromosome anomalies was different in the various histological types, and a significant difference was found between the meningotheliomatous (23%) and psammomatous (58%) types. The cytogenetically abnormal cases of the psammomatous type all showed involvement of chromosome 22. In three patients with multiple meningiomas, we found different karyotypes in the different tumors of the same patient, which may indicate a multifocal origin of the tumors. PMID- 2317773 TI - Monosomy 3 and isochromosome 8q in a uveal melanoma. AB - Chromosome analysis of a locally invasive uveal melanoma revealed monosomy 3 and i(8q). Sublines with multiple copies of the i(8q) were also present. Loss of heterozygosity for genes on chromosome 3 and duplication of genes on 8q may play an important role in progression of uveal melanoma. PMID- 2317774 TI - Translocation t(11;13) and deletion of chromosome 7 in a patient with acute myelomonocytic leukemia. AB - A translocation between chromosomes 11 and 13, together with a deletion of the long arm of chromosome 7, was found in the bone marrow of a patient with acute myelomonocytic leukemia (AMMOL). All three breakpoints are believed to be associated with a predisposition to malignancy. PMID- 2317775 TI - Trisomy 4 in a case of acute undifferentiated myeloblastic leukemia with hand mirror cells. AB - A case of acute undifferentiated myelocytic leukemic with trisomy 4 is described. The patient is a 61-year-old woman who developed leukemia 4 1/2 years after receiving radiation therapy for uterine carcinoma. Many leukemic cells exhibited hand-mirror configuration after the bone marrow aspirate was left at room temperature overnight. The relationship between trisomy 4 and hand-mirror cells in acute myelocytic leukemia is unknown. PMID- 2317776 TI - Clonal duplication of the Y chromosome and fra(X)(q28) in a case of epidermoid carcinoma of the esophagus. PMID- 2317778 TI - The nature of non-disjunction. PMID- 2317777 TI - Pseudodicentric isochromosome(22) in meningiomas. PMID- 2317779 TI - Changes in diacylglycerol and membrane associated protein kinase C activity reflect the growth status of xenografted human mammary carcinoma treated with 8 Cl-cAMP. AB - The intracellular accumulation of cAMP inhibits the growth of transformed cells in vitro and in vivo, and exposure to various cAMP analogs produces similar results. The influence of such analogs on the growth of neoplastic cells in vivo is less well defined, and the relevance of these analogs for the phosphoinositide pathway has not been established. The present report details the inhibition of tumor growth that occurred when human mammary xenografts were treated with 8-Cl cAMP, the subsequent rebound in tumor growth that occurred when treatment ceased, and the levels of diacylglycerol and membrane-associated protein kinase C activity that characterized tumors in different growth states. Tumor levels of diacylglycerol and particulate PKC activity appeared to be influenced not only by treatment but also by treatment withdrawal. Changes in these entities tended to coincide with tumor growth rate, being relatively suppressed during growth stasis and markedly elevated during periods of rapid growth. The data presented do not establish a causal relationship. Thus, the concomitant changes noted in tumor growth and tumor levels of either diacylglycerol and membrane-associated protein kinase C may only be coincidental. Alternatively, they may indicate that cAMP analogs inhibit tumor growth in vivo by modulating the phosphoinositide pathway. PMID- 2317780 TI - Cancer mortality and some socio economic correlates in Rosario, Argentina. AB - The age-standardized mortality rates by sex for cancer of all sites and some specific sites were calculated in the 22 areas of Rosario (Argentina). The rates by area were correlated with education, occupation, housing quality and population density, applying Kendall's tau. Cervical cancer rates showed the strongest correlations, which were positive with illiteracy, unqualified occupations and poor housing. These variables presented positive correlations with stomach cancer also, which were more significant in males than in females. Colon and breast cancer rates had positive correlations with the highest levels of education, occupational status, housing conditions and population density. PMID- 2317781 TI - Modification of DNA by bile acids: a possible factor in the etiology of colon cancer. AB - Bile acids have been implicated as promoters and cocarcinogens in the etiology of colon cancer and as comutagens and mutagens in bacteria. These observations suggest the hypothesis that bile acids may interact directly with DNA. We treated the single stranded circular DNA of phage M13 with bile acids and found that the transfection efficiency of this DNA declined up to a 1000-fold. This result suggests that bile acids can damage DNA and thus may play an important role in the etiology of colon cancer. PMID- 2317782 TI - Usefulness of rapid production model for pancreatic carcinoma in male hamsters. AB - The rapid production model of pancreatic duct adenocarcinoma established previously in female Syrian hamsters was applied to male hamsters to confirm the efficacy of the "augmentation pressure" procedure and to reveal sex difference in response to this procedure. Hamsters received 70 mg/kg N-nitrosobis (2-oxopropyl) amine (BOP) as an initiation and two cycles of "augmentation pressure" consisting of ethionine on a choline-deficient diet, methionine and BOP and an additional 20 mg/kg BOP and were killed 10 weeks after the beginning of the experiment. During the experimental period, 28% of the hamsters died and severe body weight loss was observed, however, incidence of pancreatic carcinomas reached 50% which is a significantly higher level than that in hamsters which received BOP without "augmentation pressure". A 66.7% yield of cholangiocellular tumors was also observed. The present result indicates that the "augmentation pressure" effected rapid production of pancreatic carcinoma in male hamsters in spite of sex difference in response. PMID- 2317783 TI - Susceptibility of RDM4 lymphoma cells to LAK-mediated lysis is decreased in tumor bearers fed fish oil high fat regimen. AB - RDM4 lymphoma cells were grown intraperitoneally in genetically compatible AKR mice fed either regular mouse chow, or diet supplemented with either saturated fat (hydrogenated beef tallow = HBT) or unsaturated fat (fish oil = FO). It was observed that the lymphoma cells number was significantly greater in FO-fed hosts and lower in HBT-fed hosts, than in the mice fed regular chow. The tumor bearers diet did not dramatically influence the rate of DNA synthesis of RDM4 cells, as measured by [3H]thymidine uptake in culture, a few hours after harvesting from the peritoneal cavity. It was repeatedly found that FO feeding of the tumor bearers elicited an increased resistance of RDM4 cells to lysis by LAK effectors, as appraised in vitro by 51Cr release test and in vivo by the "Winn assay". Different FO percentage of the diet (16%, 8%, 4%) resulted in comparable reduction of susceptibility of RDM4 cells to lysis by LAK effectors. Lipid analysis showed that RDM4 cells grown in mice fed FO diet or HBT diet differed markedly in their fatty acid composition and that their resistance to lysis by LAK cells correlated with the quantity of oxidizable fatty acids especially of the n-6 type. PMID- 2317784 TI - Effect of dietary aromatic isothiocyanates fed subsequent to the administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumorigenicity in mice. AB - Naturally-occurring aromatic isothiocyanates, benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC), were tested for their post-treatment effects on lung tumorigenicity by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone (NNK) in A/J mice. Mice at 7 weeks of age were administered a single i.p. dose of NNK (10 mumol/mouse). One week after NNK dosing, mice were placed on AIN-76A diet containing 1 or 3 mumol/g diet of BITC or PEITC. The control group was maintained on AIN-76A diet after NNK administration. Mice were killed 16 weeks after NNK treatment and lung adenomas were counted. The results showed mice fed control diet developed 7.8 tumors/mouse. Mice fed PEITC at concentrations of 1 or 3 mumol/g diet had 8.2 or 6.1 tumors/mouse, respectively. Feeding BITC at 1 mumol/g diet resulted in a tumor yield of 8.0 tumors/mouse, whereas BITC diet at 3 mumol/g diet gave 5.2 tumors/mouse, a small but significant inhibition. However, in the high BITC dose group, a loss in weight gain due to reduced food intake was noted. The results of this study showed that post-treatment of aromatic isothiocyanates had little, if any, effect on NNK lung tumorigenicity in A/J mice. This is in contrast to our previous findings in which pretreatment with PEITC greatly inhibited lung tumor induction by NNK in A/J mice and suggests that tumor inhibition by PEITC is due to inhibition of NNK metabolic activation. PMID- 2317785 TI - Effect of DL-buthionine-S,R-sulfoximine on 1,2-dimethyl-hydrazine-induced colonic tumors in rats. AB - The effect of DL-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of glutathione biosynthesis, on colon tumor development was studied in rats. Weanling male Sprague-Dawley rats were randomly assigned to one of three groups following a week of adaptation. Group 1 rats received BSO (4.5 mM) daily in the drinking water one week before 1,2-dimethylhydrazine (DMH) injections and continued to receive BSO daily until sacrificed; group 2 rats received BSO (4.5 mM) after the last DMH injection, and continued to receive BSO daily until sacrificed; group 3 rats did not receive BSO. All experimental rats received 20 weekly subcutaneous injections of DMH (20 mg/kg body wt.) for colon tumor induction. The tumor incidence was lower in group 1 (54%) than in group 2 (97%) or group 3 (96%). The median tumor size is significantly smaller in group 1 (11 mm2) than group 3 (46 mm2). The group 2 had the largest median tumor size (65 mm2). PMID- 2317786 TI - Retinoic acid inhibition of human breast carcinoma proliferation is accompanied by inhibition of the synthesis of a Mr 39,000 protein. AB - Retinoic acid (RA) inhibits proliferation of numerous breast carcinoma cells and prevents estrogen stimulation of growth of several estrogen receptor (ER) positive cell lines. RA inhibition of human breast carcinoma cell proliferation is associated with marked inhibition of the synthesis of a Mr 39,000 protein in the ER-positive human breast carcinoma cell lines investigated. Inhibition of the synthesis of the Mr 39,000 protein occurred within 24 h of RA addition and coincides with the onset of inhibition of cellular proliferation. Increasing the dose of RA results in increasing inhibition of Mr 39,000 synthesis. RA does not inhibit the proliferation of the ER-negative human breast carcinoma cell line MDA MB-231; synthesis and inhibition of the Mr 39,000 protein is not noted in this cell line. Tamoxifen, which inhibits ER-positive breast carcinoma proliferation, moderately inhibits Mr 39,000 synthesis, while a concentration of difluoromethylornithine which inhibits cellular proliferation by greater than 50% does not affect Mr 39,000 protein synthesis. Thus, inhibition of the Mr 39,000 protein appears not to be simply related to the cessation of cellular proliferation. PMID- 2317787 TI - Expression of alternatively terminated unusual human butyrylcholinesterase messenger RNA transcripts, mapping to chromosome 3q26-ter, in nervous system tumors. AB - To study the molecular origin of the altered regulation of butyrylcholinesterase (BuChE) in nervous system tumors, BuChE complementary DNA (cDNA) sequences from human glioblastoma and neuroblastoma cDNA libraries were compared with BuChE cDNAs from normal fetal and adult tissues. A single 2.6-kilobase BuChE cDNA sequence was found in all normal tissues, whereas an additional alternatively terminated BuChE cDNA clone was found in both tumor libraries. The tumor-specific cDNA contained a 3',0.7-kilobase nontranslatable extension, as well as several nucleotide alterations in the normal polyadenylation site. Single-base mutations in the coding region of this unusual BuChE cDNA infer two amino acid substitutions: Asp70----Gly and Ser425----Pro. The Asp70----Gly change has recently been implicated with "atypical" BuChE, which is deficient in its capacity to hydrolyze succinylcholine. The 3.6-kilobase mRNA was less abundant in RNA blot hybridization than the 2.6-kilobase mRNA, which is in agreement with the low ratios between the 3.6- and 2.6-kilobase BuChE cDNA clones in glioblastoma and neuroblastoma libraries. Furthermore, size fractionation and microinjection of glioblastoma polyadenylated RNA, followed by enzyme activity and selective inhibition measurements, demonstrated two peaks of functional BuChE mRNA, the heavier one probably reflecting the longer transcripts. Chromosomal mapping of the 0.7-kilobase 3' fragment by in situ hybridization localized it to a unique 3q26-ter position, where we recently found an inheritably amplified "silent" defective CHE gene in a family exposed to the cholinesterase inhibitor methyl parathion. Our findings confirm previous genetic linkage mapping of the functional CHE gene to the 3q26-ter position and demonstrate that extended functional mRNA transcripts encoding a BuChE form with two modified amino acids are produced from this gene in glioblastoma and neuroblastoma cells. PMID- 2317788 TI - Retinoid modulation of estradiol-stimulated growth and of protein synthesis and secretion in human breast carcinoma cells. AB - All-trans-retinoic acid (RA) has been demonstrated to inhibit the growth of numerous breast carcinoma cell lines. In this study we demonstrated that RA inhibits estradiol stimulation of proliferation of the estrogen-dependent breast carcinoma cell lines MCF-7 and ZR-75. RA inhibition of MCF-7 breast carcinoma cell proliferation is associated with the marked stimulation of the synthesis and secretion of a 75,000 molecular weight protein. Minor stimulation of the synthesis and secretion of other proteins was also noted, including 160,000, 95,000, 89,000, 82,000, 52,000 and 46,000 molecular weight proteins. Increased synthesis and secretion of the Mr 75,000 protein was noted with as little as 10 nM RA. Stimulation of the synthesis and secretion of this protein occurred within 24 h of adding the retinoid and at the time of RA inhibition of cellular proliferation. RA stimulated the production and secretion of this protein both in the absence and presence of estradiol. Stimulation of the secretion and synthesis was not noted in the presence of difluoromethyl-ornithine or tamoxifen, both of which significantly inhibited cellular proliferation. The estrogen-dependent breast carcinoma cell line ZR-75 when exposed to RA also expressed increased synthesis of the Mr 75,000 and 46,000 proteins but increased synthesis was not noted in the RA-resistant cell line MDA-MB-231. Stimulation of the synthesis and secretion of the Mr 75,000 and/or 46,000 proteins may be intimately involved in RA inhibition of cellular proliferation. PMID- 2317789 TI - Pharmacokinetics of recombinant interleukin 2 in humans. AB - This report summarizes the pharmacokinetics in humans of recombinant interleukin 2 (IL-2) given as an i.v. bolus, i.v. or i.p. infusion, and i.m. or s.c. injection. Immediately after an i.v. bolus the serum IL-2 level equals the dose divided by the plasma volume, in a typical human 650 units/ml for a dose of 10(6) units/m2. The level initially decreases with a half-life of 12.9 min, followed by a slower phase with a half-life of 85 min out to 4 h after the bolus. The median steady state level during an i.v. infusion of 10(6) units/m2 over 6 h is 41 units/ml. A clearance rate of approximately 120 ml/min is obtained from either the i.v. bolus or infusion data and is consistent with the renal filtration being the major route of clearance. Serum levels remain fairly constant for about 8 h after s.c. or i.m. injection but are approximately 2% of the level seen immediately after an i.v. bolus. The area under the time-concentration curve suggests that about 30% of the IL-2 activity is transported from the site of an i.m. injection to the blood. After i.p. infusion IL-2 is only slowly transported to the blood. The median serum IL-2 levels are 430-fold lower than levels in the i.p. fluid and decrease with a median half-life of 6.3 h. PMID- 2317790 TI - Potentiation of invasive capacity of rat ascites hepatoma cells by adriamycin. AB - The effect of Adriamycin on the invasive capacity of rat ascites hepatoma cells, W1, was studied. The invasive capacity of W1 cells was estimated in vitro by counting the number of penetrated single tumor cells and tumor cell colonies formed from the penetrated cells underneath a cultured mesothelial cell monolayer (H. Akedo et al., Cancer Res., 46: 2416-2422, 1986). A considerable increment of the invasive capacity was observed when the tumor cells had been treated with 1.0 to 20.0 microM Adriamycin. This augmentation of invasive capacity of tumor cells was partially inhibited by 60 microM N-acetylcysteine, a scavenger of free radicals. On the other hand, 60 microM N-acetylcysteine did not impair the cytotoxicity of Adriamycin for W1 cells measured by an in vitro tetrazolium-based colorimetric assay for cytotoxicity. PMID- 2317791 TI - Expression of chromosomal proteins HMG-14 and HMG-17 in transformed human cells. AB - The relation between cellular phenotype and expression of chromosomal high mobility group proteins 14 and 17 (HMG-14 and HMG-17) has been examined in human cell lineages. Quantitation of HMG-14 and HMG-17 mRNA in several human cell lines revealed differences in both the steady state mRNA level and in the ratio of HMG 14 to HMG-17 mRNA. Analysis of phenotypically distinct derivatives of human bronchial epithelial cells revealed small differences between both the steady state mRNA levels and the relative amount of these proteins among the clonal variants. The effect of myeloid differentiation on the mRNA level of HMG-14 and HMG-17 was examined in the human promyelocytic leukemia cell line HL-60 following treatment with several granulocytic and monocytic differentiating agents. The ratio of HMG-17 mRNA to either HMG-14 or histone H4 mRNA varied among the cell phenotypes suggesting that phenotype switching may result in detectable alterations in the expression of the HMG-14 and HMG-17 genes. The data suggest that, although the ratio of HMG-14 to HMG-17 mRNA varies among human cell lines, these variations are relatively small. PMID- 2317792 TI - Effects of smoking and irradiated volume on inflammatory response in the lung of irradiated breast cancer patients evaluated with bronchoalveolar lavage. AB - Quantitative measurements of the effects of irradiation on normal tissues in humans have been hard to obtain because most tissues are inaccessible and/or direct responses are difficult to quantify in a nondestructive manner. Pneumonitis and fibrotic lung disease are adverse effects seen in varying intensity in patients treated with radiotherapy for carcinomas of the thorax, e.g., breast cancer. In the present study the aim was to evaluate the inflammatory reaction in the underlying parenchyma following postoperative irradiation with bronchoalveolar lavage technique. Twenty-one patients (11 smokers, 10 nonsmokers) with breast cancer stage T1N0M0 received radiotherapy with photons to a target dose of 56 Gy following breast conservative surgery. Nineteen healthy controls were also included. The results showed a clear elevation of neutrophils, mast cells, eosinophils, and lymphocytes in the total irradiated groups, compared to controls. When subclassifying the material according to smoking habit, it was obvious that the smokers displayed a significantly decreased inflammatory reaction, i.e., reduced levels of mast cells and lymphocytes, compared to both nonsmoking controls and patients. Eosinophils were seen in an elevated number in all irradiated patients. Radiological signs of pneumonitis were observed in three patients, all in the nonsmoking group. No correlation was found between the volume of lung irradiated and the inflammatory response. It is concluded that bronchoalveolar lavage is a suitable and sensitive method for investigating radiotherapy-induced reactions in the human lung. Furthermore, ongoing smoking during the treatment depressed the inflammatory response in the lung parenchyma induced by irradiation. The present study as well as earlier observations justify further studies concerning the possibility of interaction of smoking with cancer treatment, both from the view of therapeutic failures and reduced adverse effects. PMID- 2317793 TI - Effect of homoharringtonine on proliferation and differentiation of human leukemic cells in vitro. AB - Homoharringtonine (HHT) is a cephalotaxine ester derived from an evergreen tree of southern China. We studied the effect of HHT on the clonal proliferation and differentiation of human leukemic cells from cell lines and patients. Dose response studies found that HHT inhibited colony formation of myeloid cell lines (50% inhibitory dose range, 7 to 12 ng/ml), lymphocytic cell lines (50% inhibitory dose range, 4 to 7 ng/ml), and fresh leukemic cells (50% inhibitory dose range, 2 to 25 ng/ml). Pulse-exposure studies showed that colony formation of HL-60 cells was inhibited 50% by HHT (10 to 20 ng/ml) at 45 h and completely inhibited at 72 h. Radioactive precursor studies using HL-60 cells showed that HHT predominantly inhibited protein synthesis as compared with RNA and DNA synthesis. Taking advantage of this, we have found that the combination of HHT with 1-beta-D-arabinofuranosylcytosine (inhibitor of DNA synthesis) was synergistic in the inhibition of HL-60 clonal growth. HHT (2 to 20 ng/ml) also was found to induce up to 28% of HL-60 cells to differentiate toward macrophage like cells. PMID- 2317794 TI - Heat radiosensitization and the level of DNA polymerases alpha and beta of human colony-forming unit-granulocyte-macrophage and myeloid leukemias sensitive and resistant to chemotherapeutic agents. AB - In these studies, heat radiosensitization in normal human colony-forming unit granulocyte-macrophage (CFU-GM) and several different leukemic cell lines sensitive or resistant to chemotherapeutic agents were measured. Extent of heat radiosensitization was then correlated with the level of DNA polymerases alpha and beta in control and heat-shocked cells in order to examine whether there is a positive correlation between the degree of heat radiosensitization and the level of these enzymes. Our results show that human bone marrow CFU-GM have an x-ray response with D0 of 1.56 Gy and a small amount of heat radiosensitization with a thermal enhancement ratio (TER) of 1.2. K562, a human erythroleukemic cell, showed a D0 of 1.32 +/- 0.2 Gy and TER of 1.4. However, in contrast to normal CFU GM which showed no shoulder in the X-ray survival curve, K562 cells showed a small shoulder with a quasi-threshold dose, (Dq) of 2 Gy and n of 2. K562 cells resistant to chemotherapeutic drugs such as 1-beta-D-arabinofuranosylcytosine and etoposide (VP-16) showed D0 of 1.47 +/- 0.13, and 1.77 +/- 0.18 Gy; Dq of 4 and 0 Gy; and n of 5 and 1; and TER of 1.6 and 2, respectively. The level of DNA polymerases alpha and beta activity and their respective mRNA levels were approximately the same in all cells. The reduction in the level of DNA polymerase beta after heat treatment however, correlated with the TER obtained for various leukemic cells. These studies indicate that normal CFU-GM and variety of human leukemic cells show only a small amount of heat radiosensitization. However, drug resistant leukemic cells show a higher amount of heat radiosensitization than their drug-sensitive parent line. This suggests that hyperthermia may be beneficial in eradicating drug-resistant leukemic cells when combined with X-ray. Furthermore, the inactivation of DNA polymerase beta activity results in a higher amount of heat radiosensitization. PMID- 2317796 TI - Nonuniform alteration of cis-diamminedichloroplatinum(II) tissue distribution in dogs with whole body hyperthermia. AB - The purpose of this study was to investigate the pharmacokinetics and tissue disposition of cisplatin (CDDP) in euthermic and hyperthermic dogs to determine if hyperthermic alteration of tissue CDDP concentration is uniform. Eighteen female beagle dogs received 20, 50, or 80 mg/m2 CDDP by constant infusion for 60 min under normothermic or hyperthermic conditions (n = 3/subgroup). Blood, plasma, and ultrafiltered plasma samples were collected during the infusion. At termination of infusion, animals were immediately sacrificed, all major tissues were collected, and platinum levels were determined by atomic absorption spectroscopy. Platinum concentrations in all blood fractions of hyperthermic dogs tended to be lower than those of normothermic dogs. The correlation between dose and blood area under the concentration-time curve was linear at both temperatures. Each tissue concentration was normalized for that individual dog's blood area under the curve. The ratio of relative extraction at 42 degrees C to that at 37 degrees C were compared for each tissue. Values of 1.0 were interpreted as indicating uniform relative tissue extraction at each temperature. Values of greater than 2.0 were obtained in lung and ileum, while values of greater than 1.5 were obtained in liver, adrenal, stomach, colon, duodenum, spleen, and pancreas. Values of less than 1.0 were obtained in skin and superficial lymph nodes. These results indicate that hyperthermia significantly alters the pattern of CDDP tissue disposition in a nonuniform manner and that pharmacokinetic data obtained at one temperature, e.g., areas under the curve, cannot be used to directly predict tissue concentrations at another temperature. PMID- 2317795 TI - Phase I trial of 5-fluorouracil and recombinant alpha 2a-interferon in patients with advanced colorectal carcinoma. AB - We have previously shown that the combination of 5-fluorouracil (5-FUra) and recombinant alpha-2a-interferon (rIFN-alpha-2a) produced objective responses in 23 of 32 (63%) previously untreated patients with advanced colorectal carcinoma. Because in vitro data suggest that rIFN-alpha-2a modulates the cytotoxic effects of 5FUra in a concentration-dependent manner, a phase I clinical trial was initiated to determine the maximum tolerated dose of rIFN-alpha 2a when administered in combination with 5FUra. A total of 27 patients with advanced colorectal carcinoma were enrolled. The median age was 64 years, and the median performance status was 1. A total of 18 patients had no prior chemotherapy and 19 no prior 5FUra. 5FUra was administered at 750 mg/m2/day by continuous i.v. infusion for 5 days, followed by weekly bolus therapy. rIFN-alpha 2a was administered at 6, 9, 12, 15, or 18 x 10(6) units s.c. beginning on day 1. The dose-limiting toxicity of this regimen was fatigue, resulting in a decrease in performance status, and this was the only toxicity that correlated with increasing dose of rIFN-alpha 2a. Eastern Cooperative Oncology Group grade 3-4 toxicities included leukopenia (6), thrombocytopenia (2), anemia (4), stomatitis (4), diarrhea (4), neurological (2), infection (2), and allergy (2). Three quarters of the patients required interruption of therapy or dose reductions of either 5FUra or rIFN-alpha 2a for toxicity. Among the patients with measurable disease who were previously untreated with 5FUra, 5 of 9 at the lowest dose levels achieved an objective response, including one pathological complete responder, whereas 0 of 9 at the three highest dose levels responded. Among patients previously treated with 5FUra, only 1 achieved an objective response. We conclude that the maximum tolerated dose of rIFN-alpha 2a, when administered with 5FUra as above, is 15-18 x 10(6) units; however, the efficacy of this regimen does not appear to be related to the dose intensity of rIFN-alpha 2a, and future regimens should employ a lower dose, intermittent schedule of rIFN-alpha 2a, which may be better tolerated. PMID- 2317797 TI - Properties of ornithine decarboxylase in human colorectal adenocarcinomas. AB - Ornithine decarboxylase (ODC) activity was measured in colon adenocarcinomas and adjacent normal-appearing colon mucosa from a total of 40 patients undergoing surgical resections. The enzyme activity was measured in the presence and absence of GTP, since recent work has demonstrated a GTP-activatable form of ODC in some murine and human tumors. In general, ODC specific activity was higher in adenocarcinomas than in adjacent normal-appearing mucosa. Of greater interest, however, was the finding that 13 of 40 tumors and 3 of 40 mucosae contained a GTP activatable form of ODC. These are minimal estimates of the proportion of tissues positive for this enzyme form, since a multiple sampling protocol indicated that expression of a GTP-activatable ODC was not uniform throughout a given tumor. Chromatographic analyses of tumor extracts revealed the presence in some tumors of multiple size forms of ODC, only some of which were activated by GTP. Enzyme kinetic data indicated that the multiple forms of ODC can have different affinities for L-ornithine and that GTP can "normalize" the aberrant kinetic properties of these forms. While there was no statistically significant correlation of the presence of a GTP-activatable ODC with stage of disease, analysis of our data revealed a positive association of a GTP-activatable ODC with tumor site; a much higher percentage of tumors of the cecum contained this ODC isoform than tumors of other colonic segments (64% versus less than or equal to 25% for other sites). These results demonstrate (a) the presence of a functionally distinct form of ODC in some human colon adenocarcinomas and (b) a distinct regional distribution of this ODC form within the colon. We suggest this alteration in a key enzyme in the growth-associated pathway of polyamine biosynthesis may play a role in colon tumor progression. PMID- 2317798 TI - Effect of calcium channel blockers on gastric carcinogenesis and caerulein enhancement of gastric carcinogenesis induced by N-methyl-N'-nitro-N nitrosoguanidine in Wistar rats. AB - The effects of the organic calcium channel blocker verapamil and the inorganic calcium channel blocker MgCl2 on gastric carcinogenesis, on caerulein enhancement of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and on the labeling index of gastric mucosa were investigated in inbred Wistar rats. After 25 weeks of treatment with N-methyl-N'-nitro-N-nitrosoguanidine (50 micrograms/ml p.o.), rats received one of the following alternate-day injections: caerulein (2 micrograms/kg body weight, s.c.), MgCl2 (150 mg/kg, s.c.), verapamil (20 mg/kg body weight, i.p.), caerulein (2 micrograms/kg body weight, s.c.) plus MgCl2 (150 mg/kg body weight, s.c.), or caerulein (2 micrograms/kg body weight, s.c.) plus verapamil (20 mg/kg body weight, i.p.). At Week 52, prolonged administration of caerulein had significantly increased the incidence and number of adenocarcinomas in the glandular stomach and the incidence of gastric cancers that penetrated through or beyond the muscle layer. Concomitant administration of MgCl2 significantly attenuated the enhancing effect of caerulein on gastric carcinogenesis. Combined administration of caerulein and verapamil did not affect the incidence and number of gastric cancers but significantly reduced the incidence of cancers penetrating through or beyond the muscle layer. Administration of MgCl2 or verapamil alone had no influence on gastric carcinogenesis. Rats treated with caerulein had a significantly elevated labeling index of the antral mucosa which was significantly decreased by concomitant administration of MgCl2 and/or of verapamil, as compared with the labeling index observed after treatment with caerulein alone. Either MgCl2 or verapamil alone had no influence on the labeling index of the antral mucosa. These findings indicate that caerulein enhances gastric carcinogenesis and that MgCl2 and verapamil attenuate this enhancement. These findings also indicate that calcium may play an important role in caerulein enhancement of gastric carcinogenesis. PMID- 2317799 TI - Prevention of fatal infections by recombinant human interleukin 1 alpha in normal and anticancer drug-treated mice. AB - The preventive capability of interleukin 1 alpha (IL-1) against bacterial infections was estimated in normal and anticancer drug-treated BALB/c mice in comparison with OK432, granulocyte colony-stimulating factor, interferons alpha and gamma, and interleukin 2. Pretreatment with IL-1 (days -4 and -2) resulted in a significantly higher survival rate in normal mice inoculated i.p. with Klebsiella pneumoniae, Pseudomonas aeruginosa or Listeria monocytogenes (day 0). The i.p. and s.c. administrations of IL-1 were equally effective for the induction of antibacterial resistance. Pretreatment with OK432 showed an equal degree of resistance to i.p. infection but was effective only by i.p. administration. Enhanced antibacterial resistance by IL-1 and OK432 was also observed in cyclophosphamide- and aminomethylpyrimidinylmethylchloroethylnitrosourea hydrochloride-pretreated (day 5) normal hosts and in cyclophosphamide-treated tumor-bearing hosts. In the case of granulocyte colony-stimulating factor (i.p. or s.c.) (days -4 to -1), a statistical difference in survival rate between granulocyte colony-stimulating factor and its vehicle-treated groups was observed in cyclophosphamide-pretreated hosts, but not in normal hosts or aminomethylpyrimidinylmethylchloroethylnitrosourea hydrochloride-pretreated hosts. Viable bacteria in the peritoneal cavity and blood at 12 h after i.p. infection of K. pneumoniae correlated well with the survival rate. In IL-1 pretreated hosts, the earlier and increased accumulation of neutrophils into peritoneal cavity after the infection was observed and the number of inflammatory cells in peritoneal cavity correlated well with the survival rate. The enhanced resistance to bacterial infection by IL-1 was suggested to be in part due to the enhanced cellular defense mechanisms. The prophylactic administration of IL-1 would be beneficial for the management of serious infections in cancer patients. PMID- 2317800 TI - Tropomyosins of human mammary epithelial cells: consistent defects of expression in mammary carcinoma cell lines. AB - Suppression of synthesis of specific tropomyosin (TM) isoforms occurs commonly in human, murine, and avian fibroblasts transformed by retroviral oncogenes or other modalities. The resulting deficiency or altered distribution of TMs may predispose the cells to microfilament instability and contribute to expression of the transformed phenotype. In this study we have asked whether defects in TM expression had relevance to human neoplasia, which arises most often in cells of the epithelial lineage rather than in fibroblasts and often is unrelated to demonstrable expression of oncogenes. TMs were characterized in normal primary human mammary epithelial cells (HMEC) and in an immortalized nontumorigenic cell line derived from them. Seven TM isoforms were identified in primary HMEC, two of which may be unique to epithelial cells. Immortalized nontumorigenic HMEC expressed the same array of isoforms. Of six established human breast carcinoma cell lines studied, all failed to express the Mr 39,000 TM isoform and five of six also lacked expression of either the Mr 38,000 or 35,000 isoform. Northern blot analysis with probes specific for the 1.1-kilobase mRNA of fibroblast TM1 detected a mRNA of this size in normal HMEC. This mRNA, which probably encodes the Mr 39,000 TM missing from all the carcinoma lines, was absent from five of the six breast cancer cell lines. These results indicate that abnormalities in TM expression in neoplastic cells are not limited to fibroblasts. The high frequency and consistent nature of such abnormalities among cell lines derived from human breast cancer raises the possibility that such abnormalities in expression of a major cytoskeletal protein may play a role in human neoplasia. PMID- 2317801 TI - Estradiol sensitivity test using contact-sensitive plates of confluent BALB/c 3T3 cell monolayers. AB - We have attempted to develop an in vitro assay system for predicting estradiol sensitivity of clinical cancer cells by measuring the effects of estradiol on the net DNA synthesis of primary culture cells. Superinoculation of neoplastic and normal cells onto confluent monolayers of a contact-sensitive cell line, which have been designated as contact-sensitive plates (CSPs), resulted in both the specific growth of the neoplastic cells and the growth inhibition of contact sensitive normal cells. The applicability of CSPs to an estradiol sensitivity test was examined in the known estradiol-sensitive, estrogen receptor-possessing cell lines, MCF-7 breast cancer and KSE-1 esophageal cancer cells. The responses of each cancer cell to estradiol were sufficiently evaluated in this assay and clearly demonstrated stimulative and inhibitive growth regulatory effects of the estradiol in MCF-7 and KSE-1 cells, respectively. A total of 38 clinical carcinomas (33 of the breast and 5 of the esophagus) were tested for their estradiol sensitivity. A statistically significant increase of cancer cell growth (P less than 0.1) in nontreated culture from the 48th to the 96th h of the primary culture on CSPs was observed in 28 of 38 overall cases (73.7%), and the evaluable data were obtained within 5 days by a sampling of 5 X 10(3) cancer cells. Most of the breast carcinomas exhibited a positive correlation between the growth-stimulative effect of estradiol in this assay and the estrogen receptor levels in the resected specimens. On the other hand, a clinical case of esophageal cancer with an estrogen receptor showed a growth inhibition of primary carcinoma cells by estradiol treatment. These results therefore indicate the feasibility of predicting individual tumor response to estradiol by using a rapid sensitivity test in vitro. PMID- 2317802 TI - Relationship of hepatic glucose production to growth hormone and severity of malnutrition in a population with colorectal carcinoma. AB - To define the influence of weight loss on the severity of metabolic abnormalities in patients with the same stage and primary site of cancer, hepatic glucose production (HGP) and nutritional status were determined in 44 patients with advanced, Stage D colorectal carcinoma and compared to values in seven cancer free controls. The colorectal cancer patients were divided into three groups based upon percentage of ideal body weight. HGP was determined in all participants after an overnight fast by using a 3- or 4-h primed, continuous infusion of [6-3H]glucose. Fasting glucose, insulin, cortisol, thyroxine, triiodothyronine, and growth hormone values were also determined. Mean HGP was significantly elevated in colorectal carcinoma patients versus normal subjects (2.35 +/- 0.89 (SD) mg/kg/min versus 1.75 +/- 0.16; P less than 0.01). The most severely malnourished group (ideal body weight less than 90%) demonstrated the greatest increase in HGP (2.98 +/- 0.73 mg/kg/min). Growth hormone mean fasting levels were significantly elevated in the colorectal carcinoma population compared to the normal subjects (2.9 +/- 3.1 ng/ml versus 0.5 +/- 0.2; P less than 0.001). The most severely malnourished group also demonstrated the highest growth hormone levels. The rate of HGP was significantly correlated with fasting growth hormone levels (r = 0.71; P less than 0.001) and not significantly correlated to cortisol, insulin, thyroxine, triiodothyronine, or glucose levels in carcinoma patients. Thus, the elevation in HGP seen in patients with colorectal carcinoma is related to the severity of weight loss and is associated with elevations in fasting growth hormone. PMID- 2317803 TI - Suppression of radiation-induced neoplastic transformation of human cell hybrids by long term incubation at low extracellular pH. AB - We have previously reported that, when 4-(2-hydroxyethyl)-1 piperazineethanesulfonic acid buffer was used in the growth medium to control pH fluctuations during the 21-day expression period of our human cell hybrid (HeLa x skin fibroblast) transformation assay, the yield of radiation-induced neoplastically transformed foci after 7 Gy of gamma-irradiation was suppressed. We now demonstrate that the observed suppression is not related to the presence of the 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer per se but rather is a function of the growth medium pH. Detailed studies reveal that incubation of the irradiated cells during the entire 21-day expression period at pH 6.7-6.8 versus pH 7.0-7.2 significantly suppressed the transformation frequency after 7 Gy, from 4.4 x 10(-4) to 4.6 x 10(-5) (accumulated data). The endpoint fraction of flasks containing foci was also significantly reduced at the lower pH. Suppression was evident whether the growth medium pH was lowered from pH 7.0-7.2 to pH 6.7-6.8 by medium exchange on day 0, 1, or 9 or even up to 15 days post-irradiation. Growth curves revealed that the population doubling time of the cells is extended and the unirradiated and irradiated plating efficiencies are lowered by long term low pH exposure. We discuss possible mechanisms for the observed suppression, in terms of the influence of low extracellular pH on cell turnover, repair of radiation damage, cell toxicity, and activity of cellular proteases. PMID- 2317804 TI - Embryonic mutation as a possible cause of in utero carcinogenesis in mice revealed by postnatal treatment with 12-O-tetradecanoylphorbol-13-acetate. AB - Although in utero irradiation at early stages induced a high incidence of somatic mutations at coat color genes in the embryos of a specified tester strain (PT x HT F1) of mice, it was not carcinogenic by itself. However, in utero-irradiated animals did develop skin tumors and hepatomas (but not leukemias) by the postnatal administration of 12-O-tetradecanoylphorbol-13-acetate. The incidence of both tumors and embryonic mutations increased with in utero doses of X-rays. Furthermore, a large reduction of tumor incidence, about 80%, was observed by low dose-rate irradiation, similar to the 75% reduction in spot size found for embryonic mutations. The tumor nodule size was also dramatically reduced by low dose-rate irradiation. Consequently, the induced incidence and size of tumors produced by 12-O-tetradecanoylphorbol-13-acetate treatment parallel those which are observed for coat color mutations as expected, because somatic mutations observed in the pigment cells must similarly occur in embryonic cells of other organs. The larger the clone of mutant cells, the greater their chance of becoming tumorigenic by 12-O-tetradecanoylphorbol-13-acetate posttreatment. These results strongly support the recent epidemiological survey showing that adult types of cancers, but not leukemias, are increasing in the atomic bomb survivors exposed in utero, since humans are continuously exposed to a variety of cancer promoting agents in contrast to experimental animals reared without such exposures. PMID- 2317805 TI - Residual damage in mouse lungs at long intervals after cyclophosphamide treatment. AB - The purpose of these studies was to quantify the effects of radiation given to mouse lungs at intervals up to 6 months after injection of the maximally tolerated dose of cyclophosphamide. In one set of experiments a single i.p. injection of 300 mg/kg of cyclophosphamide was followed at either 1, 3, or 6 months by a range of single doses of gamma-rays delivered to the whole thorax only. In a second set of experiments mice were given five daily i.p. injections of cyclophosphamide, 100 mg/kg, followed at 1, 3, and 6 months by a range of fractionated doses of X-rays. Breathing rate, histology, and mortality were used to assess lung damage. These data were compared with age-matched animals given either the drug alone or single doses of radiation alone. Dose-response curves of lethality were constructed and fitted by a logit program, and 50% lethal doses with 95% confidence limits were determined at monthly intervals after irradiation. Dose enhancement factors were then calculated at this isoeffect for the mice given the drug and radiation. Deaths from radiation pneumonitis occurred as early as 6 weeks in mice given cyclophosphamide before irradiation; few deaths occurred after 26 weeks. However, in the mice given radiation alone, deaths from pneumonitis did not occur before 12 weeks. Cyclophosphamide given as either single doses or fractionated doses at all three times before irradiation enhanced radiation pneumonitis in mouse lung. Dose enhancement factors of 1.2, 1.4, and 1.3 were obtained when single doses of radiation followed single doses of cyclophosphamide at 1, 3, and 6 months, respectively. The dose enhancement factor for radiation pneumonitis after the fractionated exposures was less, 1.1, and was independent of time between the two treatments. An enhancement factor of 1.2 was observed for the later wave of lung damage in those few studies available for analysis at this time. These data clearly show that prior treatment of the animal with cyclophosphamide significantly reduces the radiation dose that can be given to the lung for as long as 6 months after drug treatment. In addition, lung damage occurred sooner when the drug was given prior to irradiation. These data indicate that the lung will be sensitive to retreatment with radiation when a full tolerance dose of cyclophosphamide precedes radiation. PMID- 2317807 TI - Association of change in body mass with breast cancer. AB - We examined the relation between maximal adult change in body mass and breast cancer in the Epidemiological Follow-up Study of the first National Health and Nutrition Examination Survey. A total of 5599 women ages 25 to 74 years at the baseline examination in 1971 to 1975 were analyzed. Adult body mass change was calculated from baseline interview questions on lowest and highest adult weights, ages at those weights, and adult height. The cohort was followed for a median of 10 years and yielded 101 cases of breast cancer. In a multivariate model adjusting for potential confounders (age, body mass, education, parity, age at first birth, menopausal status, calorie and alcohol intake, and physical activity) the relative risk estimates for the upper two tertiles of body mass gain were 1.7 (95% confidence interval, 0.9 to 3.4) and 2.5 (95% confidence interval, 1.2 to 5.4), respectively, in comparison to the lowest tertile of adult body mass gain. The relative risk estimate for those with a loss in body mass during adulthood was 1.3 (95% confidence interval, 0.7 to 2.6) in comparison to those in the lowest tertile of adult body mass gain. There was no association between body mass at the baseline examination and subsequent breast cancer. The results of this study suggest that gain in adult body mass is a predictor of breast cancer risk independent of adult body mass. These results also suggest that avoidance of marked weight gain during adult life may reduce the risk of breast cancer. PMID- 2317806 TI - Differential effect of gestation stage on benzo(a)pyrene-induced micronucleus formation and/or covalent DNA modifications in mice. AB - Benzo(a)pyrene (BP), an environmental carcinogen, binds ubiquitously to the DNA of maternal and fetal tissues (Lu et al., Cancer Res., 46: 3046-3054, 1986). These studies further investigated the effect of gestation age on the induction of genetic damage by BP. Timed-pregnant ICR mice were treated with one dose of BP on various days of gestation and sacrificed 24-120 h after treatment. At the molecular level, BP covalently bound to the DNA of adult bone marrow and fetal liver of mice at all gestation ages. Compared to the nonpregnant mice (adduct level = 15 adducts/10(8) bases), the adduct levels in the pregnant adult bone marrow were decreased up to 50% during early gestation (days 3-9) and then increased steadily to a 4-fold excess over nonpregnant values during late gestation (days 15-18). In the fetal liver, adduct levels exhibited little variation (3-4 adducts/10(8) bases) between days 11 and 15 of gestation and then increased sharply to 14 adducts/10(8) bases after day 16. At the cellular level, a higher percentage of polychromatic RBCs from adult and fetal mice after BP treatment contained micronuclei (MN) than controls (solvent or untreated). Bone marrow from pregnant mice exhibited greater increases in the formation of MN during early gestation (days 3-9) relative to late gestation (days 15-18), compared to the nonpregnant mice. In the fetuses, the amounts of MN formed were higher than those found in the adult nonpregnant or maternal mice, but these amounts decreased with gestation progression. Thus, MN induction with gestation progression differed from DNA adduction in adults and fetuses. In addition, the dose and time responses of MN formation also differed from those of covalent DNA modifications, when analyzed in the bone marrow of pregnant mice treated on gestation day 5. Collectively, our results showed that pregnancy and development modulate different types of genetic damage in different ways. Fetal tissues may be more sensitive than maternal tissues to genetic damage. Factors in addition to DNA adduct formation may be responsible for MN induction. PMID- 2317808 TI - Uptake of the cation hexakis(2-methoxyisobutylisonitrile)-technetium-99m by human carcinoma cell lines in vitro. AB - Uptake of the cationic compound hexakis(2-methoxyisobutylisonitrile)-technetium 99m ([99mTc]MIBI) was examined in nine human tumor cell lines. The concentration of [99mTc]MIBI after a 1-h incubation with the compound varies from 5 to 28% of the activity in the external medium. In contrast, normal V79 cells (Chinese hamster lung fibroblasts) and human peripheral blood mononuclear cells exhibit a minimal uptake of less than 2% of the activity in the medium. Kinetic experiments with SW-13 cells indicate a rapid uptake over time (t1/2 of 10 min) until a steady state is approached whose concentration appears directly correlated with the extracellular concentration of [99mTc]MIBI with no evidence of saturation over the range tested (10(-12)-10(-9) M). [99mTc]MIBI is taken up by a temperature dependent process that is restricted to living cells. Microautoradiography demonstrates that [99mTc]MIBI is clustered in the cytoplasm around the nucleus. Given that depolarizing the plasma membrane potential in high K+ buffer results in lowering the uptake of [99mTc]-MIBI and that alteration of the mitochondrial membrane potential with valinomycin or nigericin induces, respectively, a significant decrease or increase of [99mTc]MIBI uptake, we propose that the plasma and mitochondrial membrane potentials play a major role in the uptake. These data suggest that the gamma emitter [99mTc]MIBI exhibits interesting tumor cell interaction characteristics with promise for in vivo tumor imaging. PMID- 2317809 TI - Cellular F-actin levels as a marker for cellular transformation: relationship to cell division and differentiation. AB - Transformation is associated with profound structural and quantitative changes in the cytoskeleton. Herein we report studies using F-actin, a major cytoskeletal protein, as a quantitative marker for transformation cells, focusing on separating the effects of the cell cycle, cell differentiation, and transformation. The model system for these studies consisted of three lymphoblastic cell lines, one untransformed line (RPMI) and two transformed lines, one (HL-60) of which can be induced to differentiate and the other (Daudi) which cannot. The relation of F-actin levels to cell cycle was studied by flow cytometry with the use of fluorescein-phalloidin to label F-actin and propidium iodide to label DNA. F-actin levels in transformed Daudi and HL-60 lines were only two-thirds that of the untransformed RPMI cells. Histograms of the distribution of F-actin showed that the transformed lines consisted of two cell populations, one having an F-actin content near that of untransformed cells and the other having much less. Cell cycle analysis showed that F-actin in untransformed cells increased 10-15% as cells entered the S compartment, remaining approximately constant through G2 + M phases of the cell cycle, but in transformed cells the major increase in F-actin occurred during G2 + M phase. Double-label studies with rhodamine-phalloidin for F-actin and KI-67 monoclonal antibody for dividing cells (cells at late G1, S, G2, and M) measured with quantitative fluorescence image analysis showed that the mean F-actin content of dividing cells was twice that of nondividing cells. These results suggested that most of the cell division-related F-actin increase occurred during late G1 phase in untransformed cells. Differentiation of HL-60 cells with dimethyl sulfoxide or retinoic acid normalized the F-actin content of the nondividing cell population, but dimethyl sulfoxide and retinoic acid produced no detectable change in F-actin in the undifferentiable Daudi cells. A tumor promoter (12-O-tetradecanoylphorphol 13-acetate) inhibits differentiation of hematopoietic cells, resulted in a 32% decrease in the mean F-actin content of RPMI cells due to the appearance of a new subpopulation of low F-actin content. The 12-O-tetradecanoylphorbol-13-acetate induced changes reversed slowly after removal of 12-O-tetradecanolyphorbol-13 acetate but more rapidly in the presence of retinoic acid. These results indicate that F-actin quantification can serve as a marker for cellular transformation and provides a tool for studying the mechanisms of cellular differentiation that may lead to a better understanding of the oncogenic process. PMID- 2317810 TI - Radiosensitive barrier to T-cell-mediated adoptive immunotherapy of established tumors. AB - This study shows that it is not possible to cause regression of the immunogenic SA-1 sarcoma by adoptive immunotherapy with tumor-sensitized T-cells, unless the tumor-bearing recipient is exposed to a sublethal dose of gamma-irradiation to remove a barrier that prevents adoptive immunity from being expressed. This barrier to adoptive immunotherapy was found to be regenerated between 2 and 4 weeks following irradiation, and its regeneration was associated with general repopulation of host T-cells. However, it was not regenerated in the absence of the thymus, thus showing that it is T-cell dependent. Evidence that it is caused by the presence of CD4+ suppressor T-cells was shown by the finding that it can be removed by depleting mice of CD4+ T-cells with anti-L3T4 monoclonal antibodies, but not by depleting them of CD8+ T-cells with anti-Lyt-2 monoclonal antibodies. Again, the barrier could be restored to irradiated recipients by infusing them with CD4+ T-cells, but not with CD8+ T-cells, from tumor-bearing donors. The barrier to adoptive immunotherapy was found to be tumor induced and to be paradoxically generated in concert with host concomitant immunity. PMID- 2317811 TI - Expression of human chromosome 2 ornithine decarboxylase gene in ornithine decarboxylase-deficient Chinese hamster ovary cells. AB - Ornithine decarboxylase (ODC) belongs to a multigene family and some of these may very well be nonfunctional (pseudogenes). We isolated an ODC gene from a human chromosome 2-specific library and transfected the gene into ODC-deficient Chinese hamster ovary cells to directly demonstrate that this ODC gene is functional and ODC is essential for cell proliferation. After screening 2.5 X 10(5) plaques using a human ODC complementary DNA probe, a typical clone with a 5.4-kilobase insert was isolated and then cloned into the HindIII site of the pGem-1 vector. One (phODC 2B1) of these clones containing a 5.4-kilobase ODC gene insert was identified. Restriction enzyme analysis and partial sequencing data revealed that phODC 2B1 contained the full length protein-coding sequences but lacked first exon and 3'-polyadenylation sequences. Primer extension analysis indicated that human ODC mRNA has homologous sequences with the ODC gene from human chromosome 2. To determine that the chromosome 2 ODC gene is functional, ODC-deficient Chinese hamster ovary cells were transfected with the ODC expression vector (phSV2B1-neo) and several G418-resistant transfectants were isolated which expressed 70- to 400-fold more ODC activity than parental or wild-type Chinese hamster ovary cells. Furthermore, these stable transfectants exhibited a higher growth rate than wild-type cells. These results indicate that the ODC gene from human chromosome 2 encodes functional ODC protein, and ODC (and its product putrescine) is required for cell growth. PMID- 2317812 TI - Transcriptional control of glutathione S-transferase gene expression by the chemoprotective agent 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz) in rat liver. AB - The substituted 1,2-dithiole-3-thione oltipraz [5-(2-pyrazinyl)-4-methyl-1,2 dithiole-3-thione] protects against the acute and chronic toxicities of many xenobiotics, including aflatoxin B1, in rodents. These protective effects are mediated, in part, through elevation of glutathione S-transferase (GST) activities. Because studies by Coles et al. [Carcinogenesis (Lond.), 6: 693-697, 1985] suggested that the detoxication of aflatoxin through conjugation with glutathione is principally catalyzed by GST homodimer YaYa, we have investigated the regulation of the gene coding for the Ya subunit in the liver of F344 rats following dietary administration of oltipraz. Overall GST activity, as measured by conjugation with 1,2-dichloro-4-nitrobenzene or 1-chloro-2,4-dinitrobenzene, as well as the levels of GST Ya protein, was elevated 1.5-fold by 24 h and maximally (2.7- to 3.5-fold) and persistently after 5 days on a purified diet supplemented with 0.075% oltipraz. Steady state mRNA levels for GST subunit Ya, as quantified by slot blot analysis using rat liver GST complementary DNA clone pGTB38, were also elevated by 24 h, with a maximal elevation of 3-fold observed at 3 days. However, mRNA levels decreased thereafter, despite continued feeding of oltipraz. Northern blot analyses demonstrated that oltipraz did not alter the size of GST mRNA. Transcriptional activity of the GST Ya gene, as determined by nuclear run-off analysis, was increased 2-fold after 24-h feeding of oltipraz, was maximally induced 2.4-fold at 3 days, and returned to near control levels at 7 days, despite sustained feeding of oltipraz. Modulation of GST activity by oltipraz was not accompanied by changes in the methylation pattern at internal sites of the GST Ya gene. These results show that the initial induction of hepatic GST activity during oltipraz exposure correlates with changes in steady state levels of GST mRNA and rates of GST gene transcription; however, the continued elevation of GST enzymatic activities and GST Ya protein levels in the face of declining GST Ya mRNA levels and transcription rates suggests that additional mechanisms may be involved in regulating GST Ya expression by oltipraz. PMID- 2317813 TI - Impact of tolerance on antitumor efficacy of tumor necrosis factor in mice. AB - Repetitive sublethal doses of tumor necrosis factor (TNF) can induce tolerance or tachyphylaxis to the toxic effects of TNF. Because tumor-bearing (TB) mice are more sensitive to the toxic effects of TNF, this study investigates whether similar tolerance occurs in TB mice and whether it affects the antitumor response of TNF. Nontumor-bearing C3H/Hen mice were treated with twice daily i.p. sublethal escalating doses of human recombinant TNF (2, 2, 3, 3, 4, and 4 micrograms i.p. every 12 h for 6 days) and were challenged 2 days later with a lethal i.v. dose (40 micrograms) of TNF. TNF-pretreated mice had 100% survival as compared to 0% survival in control mice previously treated with saline (P less than 0.01). Tumor-bearing C57BL/6 mice bearing an MCA-106 or MCA-102 sarcoma were treated with an identical TNF-tolerizing regimen (2, 2, 3, 3, 4, and 4 micrograms i.p. every 12 h for 6 days) beginning 3 days following tumor inoculation and were similarly more resistant to a subsequent 100% lethal i.v. treatment dose of TNF than control TB mice. A significantly greater percentage of TNF-pretreated mice bearing the MCA-106 sarcoma survived treatment doses of 8, 12, and 16 micrograms of TNF i.v. than control TB mice. Similarly, a significantly greater percentage of TNF-pretreated mice bearing the MCA-102 sarcoma survived treatment doses of 6 and 9 micrograms of TNF i.v. than control TB mice. However, the ability to administer higher doses of TNF i.v. to TNF-pretreated TB mice did not improve therapeutic efficacy. In mice bearing the MCA-106 tumor the most efficacious treatment responses were seen in animals that were previously naive to TNF, and treatment toxicity (lethality) correlated directly with antitumor efficacy such that larger treatment doses of TNF in tolerant mice resulted in similar antitumor effects as smaller treatment doses in control TB mice. In mice bearing the MCA 102 tumor, equitoxic treatment doses of TNF produced similar antitumor effects in both control and tolerant TB mice. There were no differences in cure rate for TNF tolerant or control TB mice bearing either tumor. The results suggest that TNF tolerance occurs in TB mice and reduces the toxicity as well as the therapeutic efficacy of TNF. PMID- 2317814 TI - An epidemiological study of precursor lesions of esophageal cancer among young persons in a high-risk population in Huixian, China. AB - The occurrence of chronic esophagitis, considered a precursor condition for esophageal cancer, among persons 15 to 26 yr of age and risk factors for the disease were investigated in Huixian, Henan Province, a high-risk area for esophageal cancer in the People's Republic of China. The 538 study subjects underwent an esophagoscopy with guided biopsies and cytology, a physical examination, an interview with a questionnaire including known and suspected risk factors for esophageal lesions, and collection of a 10-ml blood sample and overnight urine. One-third of the subjects was selected from households with a case of esophageal cancer in the past 6 yr and two-thirds came from control households. Histologically confirmed very mild, mild, and moderate esophagitis was observed in 31.6%, 10.7%, and 1.1% of 354 male and 30.4%, 4.3%, and 1.1% of 184 female subjects, respectively. In the multivariate case-control analysis of mile and moderate esophagitis compared with very mild esophagitis and normal subjects, the prevalence of mild and moderate disease was found to be positively associated with the consumption of burning hot beverages [odds ratio (OR) = 4.7], the prevalence of esophagitis among siblings (OR = 4.4), and family history of esophageal cancer (OR = 1.8) and negatively associated with the frequent consumption of fresh fruits (OR = 0.3) and wheat flour products (OR = 0.4). Weaker associations were seen for cigarette smoking and the use of cottonseed oil as the main cooking oil. Univariate associations seen with a clinical diagnosis of oral leukoplakia (OR = 2.7) and seborrheic dermatitis (OR = 3.7) are probably due to common risk factors such as smoking and nutritional deficiency. The present findings suggest that exposures early in life to environmental risk factors and nutritional deficiency may be responsible for inflammation and a weakened esophageal epithelium, resulting in a condition possibly more favorable for the development of esophageal cancer. PMID- 2317815 TI - Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma. AB - The parent Shionogi mouse mammary carcinoma is androgen dependent but cells that survive hormone withdrawal progress and give rise to an androgen-independent tumor. To determine whether renewed growth might be attributed to the persistence or partial recovery of an androgenic stimulus, we compared the amount of dihydrotestosterone and nuclear androgen receptor in parent and recurrent tumors. The whole tissue concentration of dihydrotestosterone in the parent tumor before castration was 1.40 +/- 0.46 (SE) as compared with 0.22 +/- 0.10 pmol/mg of DNA in the recurrent tumor. The initial concentration of nuclear androgen receptor in the parent was 0.65 +/- 0.12 pmol/mg of DNA; this was reduced to zero within 24 h after castration. Also in keeping with the androgen independence, no receptor was detected in the nuclear fraction of the recurrent carcinoma. In an attempt to relate malignant potential to nonhormonal factors associated with progression, we compared the proportions of androgen-dependent and -independent tumorigenic (stem) cells in parent and recurrent tumors using an in vivo limiting dilution assay. The difference observed, i.e., one stem cell per 4000 tumor cells in the parent versus one stem cell per 200 tumor cells in the recurrent carcinoma, was consistent with a marked enrichment of stem cells in the latter. The proportion of androgen-independent stem cells was also determined by assaying tumor takes in female hosts. The difference, i.e., one stem cell per 370,000 tumor cells in the parent versus one stem cell per 800 tumor cells in the recurrent carcinoma, demonstrated a striking 500-fold increase in androgen-independent stem cells resulting from androgen withdrawal. Unexpectedly, no enrichment of androgen independent stem cells was evident in regressing parent tumors; rather, the proportion of such cells was very small, i.e., one androgen-independent stem cell per 2,200,000 regressing parent cells. This finding implies that the androgen independent state of cells which survive androgen withdrawal may result from the ability of a small number of initially androgen-dependent stem cells to adapt to an altered hormone environment. PMID- 2317816 TI - Cancer mortality in women with thyroid disease. AB - A retrospective follow-up study of 7338 women with either nontoxic nodular goiter, thyroid adenoma, hyperthyroidism, hypothyroidism, Hashimoto's thyroiditis, or no thyroid disease was conducted. All women patients at the Massachusetts General Hospital Thyroid Clinic who were seen between 1925 and 1974 and who were treated for a minimum of 1 year were traced. A total of 2231 women (30.4%) were dead and 2012 women (27.4%) were alive as of December 31, 1978. Partial follow-up information was available for the remaining 3095 women (42.2%). The average length of follow-up was 15.2 years. When losses to follow-up were withdrawn at the time of their loss, the standardized mortality ratios (SMR) for all causes of death were 1.2 [95% confidence interval (CI), 1.1-1.3] for women with nontoxic nodular goiter, 1.2 (95% CI 1.0-1.3) for those with thyroid adenoma, 1.4 (95% CI 1.3-1.5) for women with hyperthyroidism, 1.5 (95% CI 1.3 1.7) for hypothyroid women, 1.2 (95% CI 0.9-1.5) for those with Hashimoto's thyroiditis, and 1.5 (95% CI 1.4-1.6) for those without thyroid disease. For deaths from all cancers, the standardized mortality ratios were 1.5 (95% CI 1.2 1.8) for women with nontoxic nodular goiter, 1.5 (95% CI 1.1-1.9) for those with thyroid adenoma, 1.2 (95% CI 1.0-1.4) for women with hyperthyroidism, 1.0 (95% CI 0.7-1.4) for the hypothyroid women, 1.2 (95% CI 0.7-2.1) for those with Hashimoto's thyroiditis, and 1.3 (95% CI 1.0-1.5) for those women without thyroid disease. When specific cancer sites were studied, excess numbers of deaths were observed from breast cancer in women with nontoxic nodular goiter (SMR = 1.6, 95% CI 1.0-2.6) and from lymphatic and hematopoietic cancer in women with nontoxic nodular goiter (SMR = 2.4, 95% CI 1.2-4.3) and thyroid adenoma (SMR = 2.7, 95% CI 1.1-5.2). An increase in thyroid cancer risk was observed in women with thyroid adenoma (SMR = 11.7, 95% CI 1.3-42.1) but was based on only two deaths. In hyperthyroid women, statistically significant increases in the number of deaths were observed from pancreatic cancer (SMR = 2.6, 95% CI 1.4-4.3) and respiratory cancer (SMR = 2.2, 95% CI 1.3-3.5), but not breast cancer (SMR = 1.3, 95% CI 0.8 1.8). When the data were stratified by the time between the onset of thyroid symptoms and death, a nonsignificant excess number of cancer deaths was observed in hyperthyroid women who died 20 or more years after their symptoms began.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2317817 TI - Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice. AB - The present study investigates a tumor model for cachectic mice. Among various murine transplantable tumors, used for assessing cytostatics, we identified colon 26 adenocarcinoma (colon 26) as capable of causing cachexia. Fifteen days after inoculation, the tumor grew to about 6% of the body weight causing substantial carcass weight loss of 3.4 g (14.5% of the carcass weight). When the tumor size was 2.7 g at 3 weeks after the inoculation, the carcass weight was 12 g less than the age-matched control. The tumor continued to grow while the mice maintained this weight, surviving for an average of 45 days. This extensive weight loss was essentially the wasting of adipose and muscle tissues. Hypoglycemia and hypercorticism occurred during the time of the weight loss. In addition, the colon 26 caused disorders of hepatic functions: the concentration of acute phase proteins in serum increased; the number of hepatic glucocorticoid-cytosol receptors decreased; and activities of hepatic catalase and drug-metabolizing enzymes decreased. On the other hand, noncachectic mice with Meth A fibrosarcoma gained weight, which was somewhat less than the control, and had neither hypoglycemia nor hypercorticism, although some mild disorders of hepatic functions were found. Mice bearing colon 26 is an appropriate model for elucidating the mechanism that causes cachexia. PMID- 2317818 TI - Serum vitamin A and subsequent development of prostate cancer in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. AB - The relation between serum vitamin A measurements made at baseline examination (1971-1975) and subsequent development of prostate cancer was examined in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (1981-1984). The analytic cohort consisted of 2440 men 50 years of age or older who were followed for a median of 10 years. A total of 84 men developed prostate cancer. The mean level of serum vitamin A was significantly lower (P less than 0.01) in prostate cancer cases than in noncases. Considered as a continuous variable or in quartiles, a statistically significant (P less than 0.005 or P less than 0.02, respectively) trend was observed for increased risk of prostate cancer with decreasing levels of serum vitamin A. Adjusted for age and race, men in the lowest quartile had a relative risk of 2.2 (95% confidence intervals, 1.1, 4.3) compared to those in the highest quartile. The elevated risk of prostate cancer associated with the lowest quartile of serum vitamin A levels did not attenuate with increasing time between blood drawing and diagnosis, suggesting that metabolic effects of early disease are an unlikely explanation of these results. The inverse association between serum vitamin A and prostate cancer incidence was independent of age at examination and several other possible confounding variables. This is the first prospective study of serum vitamin A and prostate cancer to include a large (84) number of cases. PMID- 2317819 TI - Heme synthesis in normal mouse liver and mouse liver tumors. AB - Hepatic cancers from mice and rats demonstrate decreased levels of delta aminolevulinic acid synthase, the rate-limiting enzyme in the heme synthetic pathway, and increased heme oxygenase, the heme-catabolizing enzyme. These findings suggest that diminution of P-450, b5, and catalase in these lesions may result from a heme supply that is limited by decreased heme synthesis and increased heme catabolism. Heme synthesis was measured in mouse liver tumors (MLT) and adjacent tumor-free lobes (BKG) by administering the radiolabeled heme precursors 55FeCl3 and [2-14C]glycine and subsequently extracting the heme for determination of specific activity. Despite reduced delta-aminolevulinic acid synthase activity in MLT, both tissues incorporated [2-14C]glycine into heme at similar rates. At early time points, heme extracted from MLT contained less 55Fe than that from BKG. This was attributed to the findings that MLT took up 55Fe at a slower rate than BKG and had larger iron stores than BKG. The amount of heme per milligram of protein was also similar in both tissues. These findings militate against the hypothesis that diminished hemoprotein levels in MLT result from limited availability of heme. It is probable, therefore, that decreased hemoprotein levels in hepatic tumors are linked to a general program of dedifferentiation associated with the cancer phenotype. Diminution of hemoprotein in MLT may result in a relatively increased intracellular heme pool. delta Aminolevulinic acid synthase and heme oxygenase are, respectively, negatively and positively regulated by heme. Thus, their alteration in MLT may be due to the regulatory influences of the heme pool. PMID- 2317820 TI - Total serum cholesterol and triglycerides and risk of breast cancer: a prospective study of 24,329 Norwegian women. AB - The association between total serum cholesterol and triglycerides and the incidence rate of breast cancer has been examined in 242 incident cases of breast cancer that developed among 24,329 Norwegian women during 11-14 years of follow up. At the time of lipid measurement they were between 35 and 51 years of age. There was an inverse relation between serum cholesterol and risk of breast cancer which was confined to women diagnosed before the age of 51. The incidence rate ratio was 0.53 (95% confidence limits, 0.32 and 0.88) for women in the highest quartile of serum cholesterol (mean = 8.52 mM = 329 mg/100 ml) compared to women in the lowest quartile (mean = 5.28 mM = 204 mg/100 ml), and the relation displayed a negative trend over quartiles of cholesterol (chi 2 for trend = 3.94, P = 0.05). No association with cholesterol was found among cases diagnosed during the initial 2 years of follow-up, whereas a strong inverse relation was observed among cases that were diagnosed during the following 4 years (chi 2 trend = 12.6, P less than 0.001). For serum triglycerides there was an overall negative, but not statistically significant, association with breast cancer incidence, which was weakened after further adjustment for body mass index and serum cholesterol. The lack of information on reproductive factors associated with breast cancer risk is a limitation of this study, since potential confounding with the results cannot be excluded. We conclude that there is an inverse relation between serum cholesterol and breast cancer risk among women diagnosed before the age of 51 years. The findings indicate that the negative association cannot easily be attributed to a preclinical effect of the cancer. PMID- 2317821 TI - Genetic and biochemical characterization of the CHO-UV-1 mutant defective in postreplication recovery of DNA. AB - The CHO-UV-1 mutant, a Chinese hamster ovary cell with defective postreplication recovery of DNA, is 2- to 4-fold more sensitive than its wild-type counterpart (CHO-77256) to the lethal effects of ethylating agents and UV radiation; it is also hypersensitive (10- to 20-fold) to some DNA-methylating and -cross-linking agents. We studied the CHO-UV-1 mutant further to define its phenotype in terms of DNA damage induction and repair, methyltransferase activity, and effects of caffeine on mutational and lethal responses. Both wild-type and CHO-UV-1 cells incurred similar levels and types of damage when exposed to UV radiation, N methyl-N'-nitro-N-nitrosoguanidine, or N-methyl-N-nitrosourea. The rate and extent of repair of Micrococcus luteus endonuclease-sensitive sites after UV irradiation or treatment with N-methyl-N'-nitro-N-nitrosoguanidine were also equivalent in these two cell types. Twenty % of the initial endonuclease sensitive sites induced in either cell line remained at 18 h after UV irradiation; approximately 8% of the sites after N-methyl-N'-nitro-N nitrosoguanidine exposure were present in both parental and CHO-UV-1 cells after a 17-h repair period. Moreover, the ability of CHO-UV-1 to resynthesize and ligate DNA during excision repair was similar to that of its parent. Neither CHO UV-1 nor CHO-77256 had appreciable levels of O6-methylguanine-DNA methyltransferase activity which ameliorates the cytotoxicity of alkylating agents. Caffeine, a known inhibitor of postreplication repair, decreased the frequency of mutation induction at the hypoxanthine-guanine phosphoribosyltransferase locus by 40-55% in CHO-77256 but not in CHO-UV-1. These results rule out defective excision repair as a factor in the hypersensitivity of the CHO-UV-1 mutant to DNA-damaging agents. Hence, this cell line appears to derive from a mutation affecting nonexcision repair processes and should be useful in clarifying the mechanism(s) of postreplication recovery of DNA in mammalian cells. PMID- 2317822 TI - Correlation between clinical response to interleukin 2 therapy and sustained production of tumor necrosis factor. AB - Twenty-five previously untreated patients with metastatic renal cell carcinoma were treated with 5-day cycles of continuous infusion of interleukin 2 (IL2) and lymphokine-activated killer cell reinfusion. Five achieved a partial response. Three patients were found to have detectable tumor necrosis factor (TNF) in serum before initiation of therapy. On the fifth day of therapy, 24 patients had circulating TNF with immunoradiometric assay whereas 13 had detectable biological activity. Two days after the end of IL2 therapy, TNF concentration (immunoradiometric assay) decreased in most cases but was still detectable in 17 patients. Thirteen patients had still circulating TNF bioactivity. Although there was no significant difference between TNF levels observed on the fifth day of therapy in the responder and nonresponder groups, 48 h after the end of IL2 infusion, both the TNF concentration and the biological activity were significantly higher in the group of responder patients. This result suggests that the clinical response to IL2 therapy in patients with metastatic renal cell carcinoma is correlated to a sustained production of TNF after the end of IL2 infusion. PMID- 2317823 TI - Hyperthermic enhancement of rhodamine 123 cytotoxicity in B16 mouse melanoma cells in vitro. AB - The effect of elevated temperature on cytotoxicity of rhodamine 123 (R123) was tested in vitro on B16 mouse melanoma cells. Simultaneous 1-h exposure to R123 and hyperthermia (43 degrees C for 1 h) resulted in marked enhancement of R123 cytotoxicity. Thermal enhancement of R123 cytotoxicity occurred at temperatures as low as 38 degrees C. Heat treatment (43 degrees C for 1 h) given immediately before or after R123 exposure (37 degrees C for 1 h) yielded no significant increase in cytotoxicity over that expected for strict additivity. The effects of heat on two mechanisms reported to be associated with R123 cytotoxicity were evaluated: (a) target inactivation by R123; and (b) R123 intracellular accumulation. Hyperthermia caused an increased rate of target inactivation by R123 and also caused an increased net intracellular accumulation of R123. This indicates that at least two mechanisms are responsible for the synergistic cytotoxicity of R123 and hyperthermia. PMID- 2317824 TI - Expression of complementary DNA and genomic clones for carcinoembryonic antigen and nonspecific cross-reacting antigen in Chinese hamster ovary and mouse fibroblast cells and characterization of the membrane-expressed products. AB - Complementary DNA clones coding for both carcinoembryonic antigen (CEA), a well characterized colonic tumor marker, and nonspecific cross-reacting antigen (NCA), a related antigen, were expressed in Chinese hamster ovary (CHO) cells and L cells (mouse fibroblasts). A genomic clone coding for CEA was also expressed in CHO cells. Positive clones were identified by fluorescence flow cytometry and enzyme-linked immunosorbent assay. Membrane location of the recombinant CEA and NCA was confirmed by indirect immunofluorescence labeling of the transfectants, followed by visualization under a fluorescence microscope. The apparent molecular weight of the expressed CEA and NCA were 180,000 and 96,000, respectively, for both cell lines, as determined by immunoblot analysis. The CEA and NCA expressed on CHO cells were sensitive to treatment with phosphatidylinositol-specific phospholipase C (PI-PLC), whereas the CEA and NCA proteins on L-cells were resistant to removal by PI-PLC. Unlike NCA, which contains three methionine residues, the only methionine in CEA is in the C-terminal hydrophobic domain. This domain in CEA was shown to be removed and replaced by a phosphatidylinositol glycan (PI-G) anchor (Hefta et al., Proc. Natl. Acad. Sci. USA, 85: 4648-4652, 1988). The recombinant CEA from both CHO cells and L-cells could be labeled with [3H]-ethanolamine (a component of the PI-G anchor) but not with [35S] methionine, whereas the recombinant NCA could be labeled with both [3H]ethanolamine and [35S]methionine. The labeling studies and PI-PLC treatment results are consistent with the CEA and NCA expressed on CHO cells possessing a PI-G anchor. The CEA expressed on the L-cell transfectants may contain a PI-G anchor which is resistant to cleavage by PI-PLC. In addition, the membrane-bound and secreted levels of CEA from the CHO and L-cell transfectants were determined. PMID- 2317825 TI - Microvascular architecture of experimental colon tumors in the rat. AB - Tumor cell proliferation is dependent upon concurrent growth of a supporting vasculature. This study aims to characterize the structural features of the microvasculature within a primary tumor model. There were 22 colon tumors induced in 16 rats by repeated administration of dimethylhydrazine. A cast of the microvessels was prepared by intraarterial administration of acrylic resin (Mercox). After corrosion of the tissue, the cast was examined by scanning electron microscopy. Tumors 2.6 to 12.0 mm in diameter were examined. Within polypoid carcinomas up to 5.7 mm in diameter, there were two distinct vascular zones, a luminal vascular zone continuous with the vasculature of normal mucosa and a central zone continuous with the normal submucosa and muscularis propria vessels. Within both vascular zones, the organization of microvessels had the same general pattern as in normal mucosa. However, in tumors with diameters greater than 5.7 mm, the vasculature was seen to be disorganized and of a greater density than normal. In the smallest tumors, few morphological changes were seen in the individual microvessels when compared to normal. However, with tumor growth, there was elongation and increased diameters of the microvessels within the tumor. Microvessels within the luminal zone of the tumors which could definitely be traced to veins had diameters of 50 to 100 microns (compared to 12 to 30 microns for normal venules). Individual microvessels varied in diameter along their course forming saccular dilations in places. Networks of frequently anastomosing microvessels were formed. Extravasation of resin occurred from some microvessels. Elongated vessels of uniform diameter which travel distances up to 2 mm without branching were seen and were probably arterioles. These appearances indicate that there are two distinct stages of development of the vasculature within primary tumors, an early phase where the tumor is supplied by the preexisting host microvessels, followed by a phase of proliferation of new vessels with abnormal morphological characteristics. PMID- 2317826 TI - Effect of dietary molybdenum on esophageal carcinogenesis in rats induced by N methyl-N-benzylnitrosamine. AB - The influence of dietary molybdenum on esophageal carcinogenesis induced by N methyl-N-benzylnitrosamine (2.5 mg per kg of body weight once a week for 20 wk s.c.) was studied in male F344 rats. The tumor incidence and tumor development in the esophagus were significantly lower in the rats in the high-molybdenum (2 ppm) diet group than in the rats in the low-molybdenum (0.032 ppm) diet group; i.e., 44.4% (0.6 +/- 0.8) and 73.2% (2.2 +/- 2.0), respectively. The molybdenum levels in the esophagus-forestomach, liver, and serum were significantly higher in the high-molybdenum diet group than in the low-molybdenum diet group. Xanthine oxidase activity in the esophagus and forestomach in the high-molybdenum diet group was significantly higher than that in the low-molybdenum diet group, whereas liver and serum xanthine oxidase activities were not significantly different between these two groups. These results suggest that xanthine oxidase in the esophagus plays a significant role in the inhibitory effect of molybdenum on esophageal carcinogenesis. PMID- 2317827 TI - Infiltrative and cytolytic activities of lymphokine-activated killer cells against a human glioma spheroid model. AB - In the present study, we investigated not only the cytotoxic effects of lymphokine-activated killer (LAK) cells on a tumor mass but also the ultrastructural cell-to-cell interaction between LAK effector cells and tumor cells during the cytolytic process within a three-dimensional solid tumor. A multicellular tumor spheroid of a human glioma cell line (U-251MG) was utilized as a solid tumor model. LAK cells were generated from peripheral blood lymphocytes of a healthy donor after stimulation by interleukin 2. Multicellular tumor spheroids with diameters of 500 microns were cocultivated with either LAK cells or nonactivated peripheral blood lymphocytes at the effector:target cell ratio of 20:1, and then time-sequential kinetic, morphological, and ultrastructural analyses were carried out. Morphological and kinetic studies showed that LAK cells directly infiltrated toward the inner areas of multicellular tumor spheroids and caused a progressive tumor destruction. In contrast, peripheral blood lymphocytes hardly exhibited such activities. Ultrastructurally, it was found that the infiltrating LAK effector cells were composed of heterogeneous subpopulations, T-like cells, and large granular lymphocyte-like cells. Both types of lymphocytes tightly adhered to the tumor cells and showed typical morphological features of killing them. PMID- 2317828 TI - Molecular analysis by electron microscopy of the removal of psoralen-photoinduced DNA cross-links in normal and Fanconi's anemia fibroblasts. AB - The induction and fate of psoralen-photoinduced DNA interstrand cross-links in the genome of Fanconi's anemia (FA) fibroblasts of complementation groups A and B, and of normal human fibroblasts, were investigated by quantitative analysis of totally denatured DNA fragments visualized by electron microscopy. 8 Methoxypsoralen (5 x 10(-5) M) interstrand cross-links were induced as a function of the near ultraviolet light dose. With time of postexposure incubation, a fraction of interstrand cross-links disappeared in all cell lines. However, 24 h after treatment, this removal was significantly lower in the two FA group A cell lines examined (34-39%) than in the FA group B and normal cell lines (43-53 and 47-57%, respectively). These data indicate that FA cells are at least able to recognize and incise interstrand cross-links, as normal cells do, although group A cells seem somewhat hampered in this process. This is in accord with data obtained on the same cell lines using another biochemical assay (D. Papadopoulo, D. Averbeck, and E. Moustacchi. Mutat. Res., DNA Repair Rep., 184: 271-280, 1987). Since the fate of cross-links in FA constituted a controversial matter, it is important to stress that two different methodologies applied to genetically well defined cell lines led to the same conclusions. PMID- 2317829 TI - Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity. AB - Administration of cyclophosphamide at a dose which is lethal to 10% of control athymic nude mice resulted in sudden death within 3 h in all mice that had been pretreated with the glutathione synthesis inhibitor L-buthionine-SR-sulfoximine. In Fischer 344 rats pretreated with L-buthionine-SR-sulfoximine, the cyclophosphamide dose producing 100% acute toxicity was lowered from 500-150 mg/kg; cardiac monitoring revealed ventricular fibrillation to be the cause of death. These and additional studies reported demonstrate that cytoplasmic glutathione is an important protectant against the cardiac and skeletal muscle toxicity of cyclophosphamide and indicate that such toxicity may be substantially increased by glutathione depletion. Since diet and many drugs (including cyclophosphamide itself) are known to affect glutathione levels, the present studies suggest that cardiac and skeletal muscle glutathione content is likely to be a clinically significant determinant of the frequency and severity of the adverse drug interactions and systemic toxicity sometimes observed during cyclophosphamide therapy. PMID- 2317831 TI - Characterization of B16 melanoma cells resistant to the CC-1065 analogue U 71,184. AB - U-71,184 is a CC-1065 analogue which is highly cytotoxic in vitro and has a broad spectrum of antitumor activity in vivo. Against B16 cells, U-71,184 was 8-fold and 253-fold more potent than Actinomycin D and Adriamycin, respectively. U 71,184 killed 90% of B16 cells at 0.01 ng/ml levels of drug in the medium, which was equivalent to an intracellular concentration of about 8 pg/10(6) cell (= 2 x 10(-8) pmol/cell). A B16 cell line resistant to U-71,184 developed after 3 months of in vitro exposure to gradually increasing concentrations of the drug. The sensitive and resistant cell lines were cloned and a B16/R clone was selected which was 60 to 100 times more resistant to U-71,184 than the cloned sensitive parent (B16/S). Cells grown in the absence of U-71,184 for 2 months retained resistance to the drug. B16/R was slightly cross-resistant only to Adriamycin but not to Actinomycin D, vinblastine, or colchicine. Among alkylating agents, it was slightly cross-resistant to Melphalan but not to 1,3-bis(2-chloroethyl)-1 nitrosourea or cisplatin. B16/R did not overexpress mdr mRNA. Therefore, this cell line does not exhibit the multidrug-resistant phenotype. Most karyotypes of B16/R had a marker chromosome which carried an aberrantly staining region apparently containing repetitive replication of the same segment. Resistance can be partly accounted for by the approximately 10-fold lesser uptake of [3H]-U 71,184 in B16/R, as compared to B16/S. B16/R was cross-resistant in varying degrees to several other CC-1065 analogues. The ratio of the 50% lethal dose of U 71,184 for B16/R, as compared to B16/S, was about 60 (i.e., R/S = 60). In comparison, the following compounds had an R/S ratio of less than 20 (i.e., modest level of cross-resistance to U-71,184): U-68,819, U-73,975, U-75,500, U 75,559, and CC-1065. In contrast, the following compounds had an R/S ratio greater than 20 (i.e., highly cross-resistant to U-71,184): U-71,184 analogues U 71,185, U-73,903, and U-75,012; U-73,975 analogues U-75,613, U-75,032, and U 73,896; and CC-1065 enantiomer U-76,915. We cannot yet explain the difference in the level of cross-resistance between these compounds in vitro. B16/S and B16/R cells were tumorigenic in mice and B16/R was resistant to U-71,184 in vivo. There was no clear indication of cross-resistance of B16/R in vivo to Adriamycin, Actinomycin D, cisplatin, or Melphalan. However, U-73,975, a compound with modest cross-resistance in vitro, was significantly cross-resistant in vivo. PMID- 2317830 TI - Studies of effects of recombinant human tumor necrosis factor on autochthonous tumor and transplanted normal tissue in mice. AB - The acute hemorrhagic necrosis of tumor nodules caused by the systemic administration of recombinant human tumor necrosis factor alpha (rhTNF-alpha) has been partially attributed to changes in tumor neovascularity. In this study, the effects of rhTNF-alpha were tested on primary autochthonous sarcomas induced in C57BL/6 mice by 3-methylcholanthrene, on spontaneous mammary tumors in C3H/HEN mammary tumor virus positive mice, and on the rejection of normal tissue transplants at different stages of maturity in C57BL/6 mice. Primary i.m. tumors induced by injection of 3-methylcholanthrene grew slowly over a 3-month period and became acutely necrotic after i.v. injection of rhTNF-alpha (2-6 micrograms). In addition, rhTNF-alpha caused a reduction in tumor area of 24% over 10 days compared to a 43% increase in tumor area in control mice receiving excipient (P2 less than 0.01). Histopathologically, tumors underwent central necrosis with a neutrophilic infiltration as was observed previously for serially transplanted tumors following rhTNF-alpha administration. Spontaneous, virally induced mammary tumors underwent a 11% regression on administration of rhTNF-alpha (4-6 micrograms) compared to a 24% growth in mice receiving excipient (P2 less than 0.05). Normal mice were grafted with syngeneic (C57BL/6) or partially allogeneic (C57BL/10 to C57BL/6) skin and were treated with a single dose of rhTNF-alpha (5 20 micrograms) i.v. at either 5, 10, or 15 days posttransplantation. rhTNF-alpha administration had no effect on the integrity of the skin grafts at any maturation point tested (syngeneic graft survival at 60 days: excipient, 35 of 36 versus 20 micrograms rhTNF-alpha, 35 of 36; allogeneic graft survival: excipient, 46 +/- 8 days versus 20 micrograms rhTNF-alpha, 48 +/- 10 days). In addition, rhTNF-alpha had no effect on the integrity of a syngeneic neonatal s.c. heart graft (graft survival at 60 days, excipient, 35 of 36 versus rhTNF-alpha, 30 of 33). Thus, although rhTNF-alpha administration led to marked necrosis and growth inhibition of vascularized tumor, no effect was observed on vascularized normal tissue transplants. To evaluate possible systemic effects of the tumor bearing state on the maturing neovascularity of normal tissue grafts, the three transplant models were studied in mice bearing a 9-day established MCA-106 s.c. sarcoma. After treatment with rhTNF-alpha (2-6 micrograms), acute necrosis and tumor size reduction was apparent in the s.c. tumors; however, no effect was seen in any of the normal tissue transplants.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2317832 TI - Kinetics of transitional tumor cell line 4909 adherence to injured urothelial surfaces in F-344 rats. AB - Prior reports have described the mechanism initially responsible for transitional tumor cell adherence and implantation on injured urothelial surfaces. This study further quantifies variables that influence the size of tumor inoculum at the injury site and thereby affect bladder tumor recurrence risk. The surface area of urothelial injury, the concentration of tumor cells in the intravesical bathing medium, the viability of tumor cells, the time of urothelial exposure to tumor cells, and the intravesical pressure were the variables studied. Increasing the surface area of urothelial injury resulted in a linear increase in the size of the tumor inoculum (r2 = 0.805, P = 0.0001). Tumor inoculum increased as a direct function of the concentration of tumor cells in the bathing medium. This relationship was linear at low cell concentrations (r2 = 0.64, P = 0.0001). Higher concentrations of tumor cells appeared to result in saturation of the system, with a relationship best described by a log/log function (r2 = 0.975, P = 0.0001). Viable and nonviable tumor cells appeared to compete for available binding sites with equal efficacy. A simple logarithmic relationship was seen for the effect of exposure time on the size of the tumor inoculum (r2 = 0.513, P = 0.0198). Tumor inoculum increased as a linear function of the intravesical pressure (r2 = 0.314, P = 0.0125). These results demonstrate a significant positive correlation between each of the experimental variables and the size of tumor inoculum. Manipulation of these variables in clinical practice may alter the size of tumor inoculum and thereby have an impact on tumor recurrence secondary to implantation. PMID- 2317833 TI - Reactivity of a monoclonal antibody to manganese superoxide dismutase with human ovarian carcinoma. AB - A monoclonal antibody against manganese superoxide dismutase was assessed for its use in detecting a marker for epithelial ovarian carcinoma. An enzyme-linked immunosorbent assay indicated that less than 1% of normal individuals had serum levels over 150 ng per ml of serum, whereas over 50% of such patients showed elevated amounts. The serum levels of manganese superoxide dismutase correlated with the clinical stage of the disease and with the effects of therapy. The antibody used reacts with cryopreserved epithelial ovarian carcinomas but not with normal adult ovary or other normal tissues. Determination of the levels of this enzyme should provide a useful method for detection and monitoring of responses to treatment of epithelial ovarian carcinomas. PMID- 2317834 TI - Re: Junya Toguchida et al., Assignment of Common Allele Loss in Osteosarcoma to Subregion 17p13. Cancer Res., 49: 6247-6251, 1989. PMID- 2317835 TI - Age-related changes in the cell kinetics of rat foot epidermis. AB - The durations of the cell cycle and its component phases have been determined for the basal layer of the epidermis of the skin from the upper surface of the hind foot of the rat using single pulse [3H]-thymidine labelling and the percent labelled mitosis (PLM) technique. Rats of three age groups were used, namely 7, 14 and 52 weeks. The duration of DNA synthesis (Ts) and the G2 plus M phase (TG2 + M) were comparable in 7-week and 52-week-old rats (P greater than 0.1). The major difference between 7-week and 52-week-old rats was in the duration of the G1 phase (TG1). In 7-week-old rats TG1 was 15.0 +/- 0.8 h and in 52-week-old rats TG1 was 31.2 +/- 3.5 h. A consequence of this variation was that the overall duration of the cell cycle was longer in 52-week-old rats (53.9 +/- 5.3 h) than in 7-week-old rats (30.1 +/- 1.3 h). Difficulties were found in fitting a simple curve to the PLM data for 14-week-old rats. This suggests that the proliferative cell population of the epidermis of rats of this age group may be heterogeneous. A satisfactory fit to the data was obtained using a computer model which assumed that the proliferative population of the epidermis of 14-week-old rats was a mixture of cells with cell cycle parameters the same as those of the 7-week and the 52-week-old rats. These two sub-populations of relatively slowly and rapidly proliferating cells were present in the ratio of 2:1. PMID- 2317836 TI - Specific expression of proteins and phosphoproteins in 3T3 T mesenchymal stem cells at distinct growth arrest and differentiation states. AB - Murine mesenchymal stem cells can be induced to arrest their growth at a series of growth and differentiation states in the G1 phase of the cell cycle. These include the predifferentiation arrest state (GD) at which the integrated control of proliferation and differentiation is mediated, the growth factor/serum deficiency arrest state (GS), and the nutrient deficiency arrest state (GN). Cells at states of reversible nonterminal differentiation (GD') and irreversible terminal differentiation (TD) can also be isolated. In this paper we have employed 1- and 2-dimensional (D) gel electrophoresis to evaluate changes in specific proteins that occur during the various growth and differentiation states of 3T3 T mesenchymal stem cells. The protein composition of membrane, microsome and cytosol preparations of cells arrested at GD, GS and GN states was determined by 2-D gel electrophoresis. More than 50 distinct polypeptides could be identified for each arrest state in gels analysed by a silver staining procedure or by autoradiography following [35S]-methionine labelling. A second series of studies established that a more limited number of differences could be identified if phosphoproteins were analysed by 1-D gel electrophoresis in cells at the GS, GD, GD' and TD states. These results established that one distinct 37 kD phosphoprotein is present in all growth arrested cells and that two distinct differentiation-associated phosphoproteins with molecular weights of 29 kD and 72 kD are present in cells at the GD' and TD states. Thus, the composition of proteins and phosphoproteins in mesenchymal stem cells serves to characterize different states of growth arrest and differentiation.2+he identification of differential PMID- 2317837 TI - In vivo effect of the tetrapeptide, N-acetyl-Ser-Asp-Lys-Pro, on the G1-S transition of rat hepatocytes. AB - The synthetic molecule N-Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), corresponding to the low molecular weight inhibitory factor preventing in vivo haematopoietic stem cell (CFU-S) entry into DNA synthesis, was tested in two heterologous systems in vivo: adult regenerating rat liver and 10-day-old rat hepatocytes synchronized by an irritating trigger. In both systems, it was shown that doses of 2-8 micrograms kg-1 of tetrapeptide inhibited 50-70% of the hepatocyte G1-S transitions. PMID- 2317838 TI - Effects of endogenous and exogenous cholesterol on the ultrastructure and steroid secretion of undifferentiated rat adrenocortical cells in primary culture. AB - The present study was undertaken to define the effects of lipoprotein-derived cholesterol and endogenous, de novo synthesized cholesterol on the ultrastructure and function of undifferentiated rat adrenocortical cells [lipoprotein (HDL3 and LDL) receptor-negative, zona glomerulosa-like adrenocortical cells] in primary culture. For this purpose human plasma high density lipoprotein (HDL3) or low density lipoprotein (LDL) was added to culture medium devoid of cholesterol. Steroid secretion remained at the low basal level even after addition of lipoproteins, and the amount of intracellular lipid droplets did not increase. When mevinolin (0.96 microgram/ml), an inhibitor of cholesterol synthesis, was added to the culture medium, a low secretion of corticosterone was measured both in serum-free and serum-containing media. Ultrastructurally, lipid droplets disappeared after treatment with mevinolin in both media used. At this concentration of mevinolin cell proliferation was similar to that in the controls, but at higher concentrations (4.8 or 9.6 micrograms/ml) proliferation was inhibited to 42% and 26% in serum-free medium, and 20% and 12% in serum supplemented medium, respectively. This study demonstrates that cell proliferation and synthesis of corticosterone by undifferentiated rat adrenocortical cells is identical in the absence or presence of exogenous lipoprotein cholesterol. Inhibition of de novo cholesterol synthesis by mevinolin over a period of 7 days does not inhibit corticosterone secretion or proliferation of cells but decreases the amount of intracellular lipid droplets, thus suggesting utilization of intracellular cholesterol esters. However, higher concentrations of mevinolin inhibit proliferation of cells both in serum-free and serum-containing media. PMID- 2317840 TI - Morphological changes in the zonula adhaerens during embryonic development of chick retinal pigment epithelial cells. AB - Retinal pigment epithelial cells from chicks at various stages of development were examined by transmission electron microscopy to determine how the adult form of the zonula adhaerens, composed of subunits termed zonula adhaerens complexes, is acquired. During early stages of development, between embryonic day 4 and embryonic day 7, the intermembrane discs of zonula adhaerens complexes appear to be formed from material already present between the junctional membranes of the zonulae adhaerentes. In contrast, the cytoplasmic plaque material of the zonulae adhaerentes is difficult to detect before hatching; it is seen as a dense band along the junctional membranes at hatching and as individual subunits in register with the intermembrane discs in adult retinal pigment epithelial cells. After embryonic day 16, when the zonulae adhaerentes increase dramatically in size, single zonula adhaerens complexes are also present basal to the zonulae adhaerentes along the lateral cell membrane. This suggests that, during later stages of development, the junctions grow in size and/or turn over by the addition of pre-assembled zonula adhaerens complexes. PMID- 2317839 TI - Cytochalasin D inhibits basal body migration and ciliary elongation in quail oviduct epithelium. AB - The effects of cytochalasin D (CD) were studied by scanning (SEM) and transmission (TEM) electron-microscopic examination at different stages of ciliary differentiation in epithelial cells of quail oviduct. Immature quails were prestimulated by estradiol benzoate injections to induce ciliogenesis in the undifferentiated oviduct. After 24 h of CD culture, SEM study revealed inhibition of ciliogenesis and dilation of the apex of non-ciliated cells. TEM study showed that 2 h of CD treatment produced dilation of lateral intercellular spaces, after 6 h of treatment, this resulted in intracellular macrovacuolation. Vacuoles were surrounded by aggregates of dense felt-like material. CD also induced the disappearance of microvilli, and rounding of the apical surface of undifferentiated cells and those blocked in ciliogenesis. Centriologenesis was not inhibited by CD; basal bodies assembled in generative complexes in the supranuclear region after 24 h of treatment. However, the migration of mature basal bodies towards the apical surface was impaired. Instead, they anchored onto the membrane of intracellular vacuoles; growth of cilia was induced in the vacuole lumen. Cilium elongation was disturbed, giving abnormally short cilia with a dilated tip; microtubules failed to organize correctly. PMID- 2317841 TI - The monoclonal antibody 22/18 recognizes a conformational change in an intermediate filament of the newt, Notophthalmus viridescens, during limb regeneration. AB - Previous work has shown that the monoclonal antibody 22/18 identifies progenitor cells (blastemal cells) which depend on the nerve for their division in the early stages of limb regeneration in the newt, Notophthalmus viridescens. This antibody also reacts with cultured cells derived from the newt limb, and the intensity of immunoreactivity appears related to cell density and differentiation into myotubes. We report here that the monoclonal antibody 22/18 recognizes a polypeptide (22/18 antigen) which is intracellular and filamentous. Double staining of cells with 22/18 monoclonal antibody and antibodies against various cytoskeletal components indicates that the epitope is expressed on an intermediate filament component. Although this antibody is specific for blastemal cells in cryostat sections of the regenerating limb, its reactivity on immunoblots is not confined to this tissue. The 22/18 antigen is differentially affected by aldehyde fixatives distinguished by the spacing of their reactive groups. While formaldehyde fixation impairs detection of the antigen, ethylene glycol-bis[succinic acid n-hydroxysuccinimide ester] reveals the antigen in sections of normal and regenerating limbs in a distribution that is consistent with the one obtained from immunoblots. We suggest that the 22/18 monoclonal antibody detects a change in protein conformation, probably related to changes in the physiological state of the cell, that occurs transiently during regeneration and possibly during development. PMID- 2317842 TI - Microvasculature of the epididymis in the boar. AB - Microvasculature of the epididymis was investigated by scanning electron microscopy of vascular corrosion casts. The basic structure of blood supply to the boar epididymis consists of two superimposed vascular networks. Capillaries surrounding the epididymal duct constitute the inner level. They form polygonal meshes around the efferent ductules whereas circular capillaries strongly predominate in the subsequent region of the caput epididymidis. This annulate feature is progressively lost from corpus to cauda, where the capillary network once again has a polygonal appearance. The outer network is composed of feeding and draining vessels. Intertubular arteries pass between the loops of the epididymal duct and give rise to longitudinally oriented vessels attributable to only one adjacent duct segment. They feed the capillary network via circular ramifications debouching in different sectors of its circumference. The sparse veins draining the capillaries encircling the efferent ductules give way to a gradually increasing number of confluent veins up to the cauda. PMID- 2317843 TI - Morphometry of the galliform cecum: a comparison between Gambel's quail and the domestic fowl. AB - Tissues from the proximal, middle, and distal regions of the ceca of Gambel's quail and domestic fowl were examined by scanning and transmission electron microscopy. Cellular and subcellular structures, including epithelial cell height, mitochondrial volume fraction, microvillous surface area, proportion of goblet cells, and junctional complex characteristics, were quantified by a variety of stereologic procedures and other measurement techniques. The mucosal surface of quail cecum shows a much more highly developed pattern of villous ridges and flat areas than that of fowl cecum. The fowl has significantly greater cell heights than the quail in all cecal regions. The mitochondrial volume fraction does not differ significantly with species or region, but mitochondria are concentrated on the apical side of the nucleus. In both species, the proximal cecal region has the greatest microvillous surface area. All 3 components of junctional complexes, including zonula occludens, zonula adhaerens, and macula adhaerens, are quantified. When all factors are considered, the quail cecum appears to have morphological characteristics consistent with a greater potential capacity for absorption than the fowl cecum. PMID- 2317845 TI - Qualitative and quantitative analysis of granules in atrial appendage cardiocytes in different physiological states. AB - Atrial appendage cardiocytes of mammals, including man, contain multiple cytoplasmic granules that vary in number in different physiological states. Using morphologic and comprehensive morphometric techniques, these granules were assessed in Sprague-Dawley rats following dehydration for 5 days, volume-loading by substituting 1% NaCl as drinking water for 7 days, unilateral nephrectomy plus volume-loading for 7 days, and in late term pregnant animals (18-20 days; term approximately 21 days). Although principally located in the paranuclear region, granules were observed throughout the sarcoplasm. Cytological features indicative of synthetic activity and granule formation were readily apparent in all groups with the exception of pregnant rats where they were infrequently observed. Granule contents were released by exocytosis and observed in the right appendage of control, dehydrated and nephrectomy/volume-loaded groups and left appendage of volume-loaded animals. Exocytosis was not observed in pregnant animals. By point counting, the proportional volume of cardiocytes occupied by granules (Vv) in controls was significantly greater for right than for left appendage (2.12 +/- 0.22% vs 1.29 +/- 0.16%; mean +/- SEM; p less than 0.05). A significantly similar difference was found for nephrectomy/volume-loaded animals. There was no significant difference in Vv for right appendage between the control and experimental groups; for left appendage there was a significant increase in Vv to 2.42 +/- 0.09% (p less than 0.05) for volume-loaded animals only. Estimation of the maximum diameter of granule profiles in control animals was 238 +/- 9 nm and 230 +/- 6 nm for right and left appendages, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317844 TI - Uptake of tritiated uteroglobin by the endometrium of the rabbit during peri implantation. AB - Uteroglobin, labelled with N-succinimidyl-(2-3-3H)-propionate, was applied in vivo for 3 h to pregnant rabbit uteri 7 and 9 days after mating. Light- and electron-microscopic autoradiographs showed that the endometrial epithelium, both ciliated and non-ciliated cells, is able to take up 3H-uteroglobin, however, with differing intensity. Large areas of labelling were found in the luminal epithelium, whereas the glandular epithelium contained fewer silver grains. Moreover, intensively labelled single cells or symplasms occurred in both luminal and glandular epithelium. They were identified as degenerating or dead cells. After internalization by pinocytosis or phagocytosis, the tritiated uteroglobin was observed in multivesicular bodies or in lysosomes with floccular content. Later, radioactivity was either found within residual bodies or distributed throughout the entire epithelium and the subepithelial stroma, i.e., the silver grains could no longer be assigned to specific cell organelles. PMID- 2317846 TI - Retinal axons in Xenopus laevis recognise differences between tectal and diencephalic glial cells in vitro. AB - Explants of retina from Xenopus laevis were cultured on monolayers of tectal and diencephalic glial cells in order to determine whether the glia, normally encountered by optic nerve fibres as they grow to the optic tectum, can influence the growth of these neurons in any way. Explants of nasal retina produced prolific radial outgrowth patterns on both tectal and diencephalic monolayers. Explants of temporal retina produced similar outgrowth patterns on diencephalic glia, but on tectal glia the outgrowth was restricted and fibres were fasciculated in short, fat bundles. PMID- 2317847 TI - Ultrastructural study of crystalloids in Sertoli cells of the three-toed sloth (Bradypus tridactylus). AB - Crystalloids were found in Sertoli cells of the testis of the three-toed sloth by examination at the light- and electron-microscopic levels. Needle-, or spindle shaped crystalloids, varying in length, were located in the basal part of the Sertoli cells. They consisted of bundles of filaments each measuring approximately 11 nm in diameter. Several filaments were packed hexagonally to form a bundle. The center-to-center distance between individual filaments of a bundle was approximately 17 nm. Periodical lateral projections emanated from the filaments. Cross sections of crystalloids showed that the projections radiated from each filament in three directions, forming an equilateral triangle with a side length of approximately 15 nm. Scattered polyribosomes were found between and around the bundles. PMID- 2317848 TI - In-vitro formation of a collagenous matrix upon previously diseased and experimentally treated cemental root surfaces. AB - A diseased and mechanically treated surface of root cementum is known, clinically, to favor periodontal regeneration. The present investigation was undertaken to test whether previously diseased and experimentally treated root surfaces can support the in-vitro formation of a new collagenous matrix. Three teeth extracted for advanced periodontitis were treated first with 5% sodium hypochlorite for 2 h to remove all organic material from the root surface. After the healthy, apical one third of the root was cut off, the roots were scaled with moderate pressure to remove visible calculus. Non-demineralized root discs were cut and placed on a co-culture of periodontal ligament- and alveolar bone-derived cells. After 7 weeks in culture, either one of two matrix types was found along the root surface. The most frequent matrix consisted of clusters of cells layered within densely aggregated collagen fibrils. The other, less frequent matrix consisted of loosely arranged collagen fibrils adjacent to the cemental surface. The findings support the notion that, in vitro, a collagenous matrix is formed in contact to diseased and experimentally treated root surfaces. However, the smooth, non-demineralized and scaled cemental surface does not appear to be a suitable substrate for interdigitation with newly produced collagen fibrils. PMID- 2317849 TI - Flunarizine in migraine prophylaxis: efficacy and tolerability of 5 mg and 10 mg dose levels. AB - The use of flunarizine, a drug which has proven its efficacy in migraine, is often associated with important side effects. The aim of this paper has been to check their incidence at different dose levels (5 mg vs 10 mg). Our data confirm the occurrence of important side effects (in particular weight gain); on the other hand, they emphasize the dose-dependency of the side effects. PMID- 2317850 TI - Subdural hematoma presenting as headache in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) affects the nervous system in 75% of cases (1). A female with several neurological manifestations in the case history presented with severe headache, psychiatric disturbances, and increasing paraparesis. She was found to have bilateral subdural hematomas, and after evacuation her neuropsychiatric symptoms, including headache, disappeared. It is speculated that the reported low incidence of subdural hematomas in SLE may be more apparent than real. On the basis of our case, we recommend repeated neuroradiological investigations to uncover this important, treatable and otherwise potentially fatal cause of headache. PMID- 2317851 TI - Opioid control of the hypothalamus-pituitary-adrenal axis cyclically fails in menstrual migraine. AB - To assess the biological correlates of the precipitation of migraine attacks in the perimenstrual period, plasma beta-endorphin (beta-EP) and cortisol responses to naloxone (8 mg iv) and corticotropin releasing hormone (100 micrograms iv) were evaluated in both the follicular phase and the premenstrual period in 7 patients suffering from menstrual migraine and in 7 healthy, asymptomatic control volunteers. In the controls, naloxone evoked a significant release of both beta EP (F = 5.86, p less than 0.002) and cortisol (F = 4.43, p less than 0.008), independently of the menstrual cycle phase (F = 0.31 and 1.04, for beta-EP and cortisol, respectively). Menstrual migraine patients, on the other hand, showed a significant hormone response only in the follicular phase, not in the premenstrual period. Corticotropin releasing hormone significantly increased beta EP and cortisol in both the controls and the menstrual migraine patients, independently of the menstrual cycle phase. In both the naloxone and corticotropin releasing hormone testings, the basal beta-EP levels measured in the premenstrual period were lower than those observed in the follicular phase (p less than 0.02). These data demonstrate a cyclical, premenstrual dysfunction of the hypothalamic control exerted by opioids on the hypothalamus-pituitary-adrenal axis. Impairment of this fundamental adaptive mechanism (involved in stress responses and in pain control) could establish a causal relationship between menstrual-related migraine attacks and premenstrual opioid hyposensitivity. PMID- 2317852 TI - Lumbar iohexol myelography and diagnostic lumbar puncture. Headache and associated side effects in relation to neurological signs and diagnosis, previous mental symptoms and pain history. AB - Various possible risk factors for postlumbar puncture (and postiohexol myelographic) headache and associated side effects were analysed. Headache and nausea occurred significantly more often in patients without clinical findings than in those with findings. We found significantly different incidences of severe headache and nausea between diagnostic subgroups after a lumbar puncture. The greatest headache incidence was found in patients without a definite neurological diagnosis, while nausea occurred most frequently in patients with various painful disorders. Following iohexol myelography, nausea occurred most often in patients who had a history of previous mental symptoms and in patients with a history of previous headache disorders. Mental symptoms were more frequently reported in patients who also had experienced mental symptoms previously. The relationship between side effects and negative clinical findings was stronger than the relationship between side effects and previous mental symptoms. PMID- 2317853 TI - Analysis of risk factors for restenosis after PTCA. AB - To identify risk factors for restenosis, we evaluated data in 473 patients with single-vessel percutaneous transluminal coronary angioplasty (PTCA) and control angiography after 6 months. Restenosis, defined as (1) loss greater than 50% of the initial gain, and (2) stenosis greater than 50% was found in 138 patients (29.2%). Univariate analysis revealed eight factors related to restenosis: (1) duration of symptoms less than 1 month (P = 0.005), (2) unstable angina (P = 0.004), (3) high-grade stenosis before PTCA (P = 0.014), (4) large residual stenosis after PTCA (P = 0.001), (5) insufficient improvement of stenosis (P = 0.042), (6) prolonged single inflation time (P = 0.017), (7) prolonged total inflation time (P = 0.055), and (8) low inflation pressure (P = 0.028). Multivariate analysis revealed four factors significantly related to restenosis: (1) large residual stenosis after PTCA (P = 0.0001), (2) prolonged single inflation time (P = 0.0047), (3) unstable angina (P = 0.0127), and (4) high-grade stenosis before PTCA (P = 0.0179). Modification of procedural factors might be helpful to reduce the risk of restenosis after successful PTCA. PMID- 2317854 TI - "High-risk" percutaneous transluminal coronary angioplasty with preventive intra aortic balloon counterpulsation. AB - Between January 1987 and February 1988, 1,385 patients underwent percutaneous transluminal coronary angioplasty; 27 procedures were performed using prophylactic intraaortic balloon counterpulsation. Twenty-four patients had poor left ventricular function (EF less than 40%), and coronary dilatation was performed in arteries opposite to an occluded myocardial necrosis related vessel. In three patients of advanced age with distal stenoses and normal left ventricular function a multivessel dilatation was performed. Primary success rate was achieved in all patients. There were no deaths, myocardial infarctions or emergency bypass operations in the hospitalization period. During the follow-up (9 to 21 months) there were 2 deaths, 1 cardiac transplantation, and 6 restenosis with repeated dilatation. If revascularization is warranted, in high-risk patients, coronary angioplasty can be performed safely and successfully with protection by intraaortic balloon counterpulsation. However the long-term prognosis of these patients is complicated by the presence of other high-risk variables, such as advanced age or poor left ventricular function. PMID- 2317855 TI - Percutaneous balloon valvuloplasty of pulmonary valve stenosis, dysplasia, and residual stenosis after surgical valvotomy for pulmonary atresia with intact ventricular septum: long-term results. AB - Eight-six children (aged 20 days to 14 years, 20 under age 1 year) underwent 94 percutaneous balloon valvuloplasty for pulmonary valve stenosis. The patients were divided into three groups: typical pulmonary valve stenosis (71), pulmonary valve dysplasia (9), and residual stenosis after surgical valvotomy for pulmonary atresia with intact ventricular septum (PAIS) (6). Each of the three groups was divided into two subgroups. In the early cases, balloon catheters with diameter 10-20% exceeding pulmonary valve annulus were used and the drop of the gradient was 39.5%. In the later cases, balloon diameters 30-40% greater than the valve anulus or double balloons were used and a drop of 66.7% in the RV-PA pressure gradient was achieved. The dilation in patients with dysplastic valve and residual stenosis after surgical valvotomy for PAIS was less effective. Doppler echocardiography was the technique used to evaluate residual gradient. Six months to 4 years follow-up demonstrated a persistent decrease of the valve gradient. PMID- 2317856 TI - Splenic abscess due to Peptostreptococcus spp. as a complication of cardiac catheterization. AB - We describe the development of a splenic abscess, due in part to Peptostreptococcus, as a complication of cardiac catheterization. The etiologies of splenic abscess should include Peptostreptococcus, and splenic abscesses should be added to the list of complications of cardiac catheterization. PMID- 2317857 TI - Iatrogenic aorto-sinus of valsalva fistula: angiographic and cine computerized tomography delineation. AB - A patient is reported who underwent cardiac catheterization 4 years following coronary artery bypass grafting. Cardiac catheterization revealed the presence of a fistulous tract in the wall of the ascending aorta, originating at the site of aortic anastomosis of a saphenous vein bypass graft and ending in the superior aspect of the right sinus of Valsalva. This complication was felt to have resulted from a inadvertent localized dissection of the aorta during bypass surgery. The fistula was also imaged by ultrafast cine computerized tomography which proved a useful non-invasive method for follow-up examination. PMID- 2317858 TI - Hugging balloon coronary angioplasty of a large left circumflex coronary artery. AB - A case is described in which hugging balloons were used to perform coronary angioplasty through a single catheter. A discussion concerning selection of balloon combinations and technique is included. PMID- 2317859 TI - Torsion of an internal mammary graft during percutaneous transluminal angioplasty: a case report. AB - A successful percutaneous transluminal angioplasty of the distal anastomosis of a tortuous left internal mammary artery graft to the left anterior descending coronary artery was complicated by the development of a focal lesion in the mid graft region. Dilatation at the site failed to improve the angiographic appearance. Withdrawal of the guidewire resulted in immediate resolution of the apparent mid-graft lesion. The abnormality is felt to have been due to torsion of the graft upon itself, caused by guidewire and balloon catheter manipulation. PMID- 2317860 TI - Swan-Ganz catheter-induced rupture of the pulmonary artery: successful early management by transcatheter embolization. AB - An 84-year-old patient with severe aortic valve stenosis suffered Swan-Ganz catheter-induced massive pulmonary hemorrhage. Immediate therapeutic embolism of the segmental artery by using a liquid, tissue-adhesive, occlusive agent (isobutyl-2-cyanoacrylate) controlled bleeding. PMID- 2317861 TI - Performance of 5 French and 7 French catheters in coronary angiography. PMID- 2317862 TI - The effects of MHC gene dosage and allelic variation on T cell receptor selection. AB - In a T cell receptor transgenic mouse model of thymic selection, the efficiency of selection of the transgenic alpha beta heterodimer is significantly enhanced in animals that express higher densities of the relevant major histocompatibility complex molecule (I-Ek/b). These results imply that there is a stochastic component to positive selection in the thymus. Allelic variants of the original selecting I-Ek molecule are either less efficient (E alpha k:E beta b) or incapable (E alpha k:E beta s and I-Ed) of mediating the selection of transgenic alpha beta + T cells. Two of these three I-E variants appear to differ from I-Ek in amino acid residues of the peptide binding site and not in residues capable of contacting the T cell receptor, suggesting that specific peptides, or conformations of peptides, play a role in positive selection. In contrast, mice transgenic for only the beta chain of this T cell receptor show selection for CD4+ T cells in the presence of all four I-E variants tested. PMID- 2317863 TI - Alternative chromatin structure at CpG islands. AB - Actively transcribed chromatin is structurally different from bulk inactive chromatin. It has been difficult to define the molecular basis of the difference, however, because purified fractions of active chromatin were not available. We have overcome this problem by releasing oligonucleosomes from the nonmethylated CpG-rich islands (CpG islands) of HeLa cell nuclei using restriction endonucleases. Since CpG islands very often include the promoters and 5' transcribed regions of genes, they represent a model for the "active" chromatin structure. CpG island chromatin differs in three respects from bulk chromatin prepared in the same way: histone H1 is present in very low amounts; histones H3 and H4 are highly acetylated; and nucleosome-free regions are present. Except for the latter regions, the average nucleosomal spacing is similar to that of bulk chromatin. PMID- 2317864 TI - A novel pathway of DNA end-to-end joining. AB - Repair mechanisms related to illegitimate recombination can join nonhomologous DNA ends that terminate as protruding single strands (PSS). Here we analyze in Xenopus egg extracts joining reactions between 3' PSS termini and various partner termini. In junctions, 3' PSS termini are preserved by fill-in DNA synthesis, although their 5' recessed ends cannot serve as a primer. Alternative priming from a partner terminus ligated to the 3' PSS end appears unlikely, because no single strand-specific DNA ligases are detectable. We show that fill-in of 3' PSS termini precedes ligation and can even be primed in the absence of any ligation. Therefore, priming requires precise alignment of terminus pairs by a novel mechanism. We postulate that this is achieved by unique DNA binding proteins that align ends in various types of joining reactions. PMID- 2317865 TI - Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. AB - cDNA clones encoding the human and murine interleukin-7 (IL-7) receptor were isolated and expressed in COS-7 cells. Binding of radiolabeled IL-7 to the recombinant IL-7 receptors produced curvilinear Scatchard plots containing high and low affinity classes. These binding properties, as well as the molecular size of the cloned receptor, were comparable to the native forms of the IL-7 receptor. In addition, several cDNA clones were isolated that encode a secreted form of the human IL-7 receptor capable of binding IL-7 in solution. Analysis of the sequence of the IL-7 receptor revealed significant homology in the extracellular domain to several recently cloned cytokine receptors, demonstrating that the IL-7 receptor is a member of a new receptor superfamily. PMID- 2317866 TI - Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. AB - We have identified a region within the steroid binding domain of the mouse estrogen receptor that is required for both receptor dimerization and high affinity DNA binding. Analysis of sequences in this region revealed that a heptad repeat of hydrophobic residues was conserved in all members of the nuclear receptor superfamily. Single amino acid substitutions of residues in the N terminal half, but not the C-terminal half, of the repeat prevented receptor dimerization. Steroid binding was abolished by point mutations in the center of the conserved region, implying that the steroid binding and dimerization domains overlap. The role of this region in steroid receptor function is discussed in relation to other models of protein dimerization and DNA binding. PMID- 2317867 TI - Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes: implications for the generation of antibody diversity. AB - Rabbits are unique in that their immunoglobulin VH regions bear allotypic markers encoded by allelic genes. The presence of these markers on most serum immunoglobulins is difficult to explain, as the germline contains several hundred VH genes. We cloned VH genes from normal rabbits of the VHa allotypes a1, a2, and a3 and from a mutant a2 rabbit, Alicia, which expresses almost no a2 allotype. The D-proximal VH gene VH1 of normal rabbits encoded prototype a1, a2, or a3 allotype VH regions in a1, a2, or a3 rabbits, respectively; VH1 was shown to be preferentially utilized in leukemic rabbit B cells. This VH1 gene was deleted from the germline of the Alicia rabbit. These data suggest that the allelic inheritance of a allotypes results from preferential utilization of VH1 in VDJ rearrangements. We suggest that antibody diversity in rabbit primarily results from somatic hypermutation and gene conversion. PMID- 2317868 TI - Maternally transmitted histocompatibility antigen of mice: a hydrophobic peptide of a mitochondrially encoded protein. AB - MTF, a murine minor histocompatibility antigen, is maternally inherited and thought to be encoded by a mitochondrial gene. We sequenced the entire mitochondrial genomes from three strains that differ in MTF Mtf beta, Mtf gamma, and Mtf delta) and compared the sequences with the known, Mtf alpha, mitochondrial DNA sequence. We found only one site where all four genomes differed, affecting amino acid residue 6 of ND1, a subunit of NADH dehydrogenase. Incubation of non-Mtf alpha target cells with synthetic peptide ND1 alpha 1-17 (the first 17 amino acid of the ND1 protein of Mtf alpha mice) rendered them susceptible to lysis by MTF alpha-specific cytotoxic T cells (CTLs). Similarly, non-Mtf beta target cells were lysed by MTF beta-specific CTLs after incubation with the allelic form ND1 beta 1-17. Thus, Mtf is attributable to allelic variation at a single residue of the ND1 protein. Cells can therefore display peptides derived from mitochondrially encoded proteins, and such peptides can be histocompatibility antigens. PMID- 2317869 TI - The product of fem-1, a nematode sex-determining gene, contains a motif found in cell cycle control proteins and receptors for cell-cell interactions. AB - We report the cloning and sequencing of fem-1, a gene required for sex determination in both germline and somatic tissues in the nematode C. elegans. Clones carrying a 5.5 kb fragment are able to rescue the progeny of a fem-1 mutant when injected into its oocytes. The major fem-1 transcript in both sexes is 2.4 kb and comprises 11 exons. It encodes a soluble, intracellular protein of 656 amino acids that includes near its N-terminus six contiguous copies of a motif found in the products of the cdc10 gene of S. pombe, the SWI6 gene of S. cerevisiae, the Notch gene of Drosophila, and the lin-12 and glp-1 genes of C. elegans. PMID- 2317870 TI - Localization of specificity determining sites in cadherin cell adhesion molecules. AB - Cadherins are a group of homophilic intercellular adhesion molecules; each member of this family exhibits binding specificity. Here, we attempted to map the sites for the specificities of these molecules by analyzing adhesives selectivities of the cells that express chimeric and point-mutated E- and P-cadherin. The results showed that the amino-terminal 113 amino acid region is essential to determine the specificities, and within this region we could identify especially important sites in which amino acid substitutions altered the binding specificity of cadherins. We also found that the epitopes for antibodies capable of blocking cadherin action are located in this amino-terminal region. PMID- 2317871 TI - sevenless: Seven found? PMID- 2317873 TI - RNK granule extract cytolysis: differential inhibitor production by an NK resistant vs an NK-sensitive murine lymphoma. AB - Natural killer (NK) cell-resistant tumors exist despite their ability to bind cells from the effector population. Tumor sensitivity to NK activity was therefore examined at the level of susceptibility to cytolysin-containing NK cell cytotoxic granule extracts. The NK-sensitive SL2-5 murine lymphoma was markedly more susceptible than the NK-resistant L5178Y-F9 to solubilized granule preparations from the rat NK tumor cell line RNK-16, and this corresponded also with tumor sensitivity to hypotonic lysis. However, the resistant L5178Y-F9 was better able to inhibit the extract activity than the SL2-5. Dissociation of the binding and lysis phases of the cytolysin reaction based on their differential temperature requirements, 4 degrees C for binding and 37 degrees C for lysis, permitted an examination of the cytolysin/tumor interaction prior to lysis. The residual cytotoxic activity was lower after extract exposure to the L5178Y-F9 compared with the SL2-5 consistent with possible inhibitor production. Finally, supernatant material collected from the L5178Y-F9 was a better inhibitor of granule extract lysis and acted preferentially in the extract-binding phase. The inhibitor appears to be protein in nature, relatively stable, and exhibits molecular weight heterogeneity ranging from 2000 to greater than 300,000. PMID- 2317872 TI - The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity. AB - Pathfinding of axons in the developing nervous system is thought to be mediated by glycoproteins expressed on the surface of embryonic axons and growth cones. One molecule suggested to play a role in axonal growth is TAG-1, a 135 kd glycoprotein expressed transiently on the surface of subsets of neurons in the developing mammalian nervous system. We isolated a full-length cDNA clone encoding rat TAG-1. TAG-1 has six immunoglobulin-like domains and four fibronectin type III-like repeats and is structurally similar to other immunoglobulin-like proteins expressed on developing axons. Neurons maintained in vitro on a substrate of TAG-1 extend long neurites, suggesting that this protein plays a role in the initial growth and guidance of axons in vivo. TAG-1 is anchored to the neuronal membrane via a glycosyl phosphatidylinositol linkage and is also released from neurons, suggesting that TAG-1 also functions as a substrate adhesion molecule when released into the extracellular environment. PMID- 2317874 TI - Hyaluronic acid promotes chick embryo fibroblast and chondroblast expression. AB - 15-day-chick-embryo fibroblasts and chondroblasts were cultured in the presence of high and low molecular weight exogenous hyaluronic acid (HA). Growth range and incorporation of radiolabelled sulphate and proline were determined. HA reduced cell proliferation to about 75% of controls, while incorporation of radiolabelled sulphate and proline was higher in HA-treated cultures of both chondroblasts and fibroblasts. The effect was not due to the polyanionic or polymeric nature of the molecule and appeared to be highly specific for HA. PMID- 2317875 TI - Factors affecting neurite outgrowth of occipital cortical explants. AB - The effects of various substrata including laminin, collagen gel, collagen I, and human amniotic basement membrane on neurite outgrowth of occipital cortical and diencephalic explants were studied. The results showed that the extent and pattern of growing neurites of cortical explants varied considerably depending on the substrata used. While an elaborated network of growing neurites was observed when cortical explants were plated on laminin, the most extensive neurite outgrowth was observed when collagen gel was used as the substratum. In contrast, diencephalic explants did not grow on most of the substrata. The significance of the findings are discussed. PMID- 2317876 TI - 5'-Nucleotidase is involved in chick embryo myoblast spreading on laminin. AB - Previous studies have shown that 5'-nucleotidase, an ectoenzyme from chicken gizzard, interacts specifically with laminin and fibronectin, two glycoproteins of the extracellular matrix. Recently, we demonstrated that 5'-nucleotidase was involved in the spreading of chick embryo fibroblast on laminin. In the present communication, we report that a monoclonal antibody (CG37) raised-directed against 5'-nucleotidase inhibited the spreading of chick embryo myoblasts on laminin after their initial attachment to the substrate. Furthermore, monoclonal antibody CG37 specifically eluted 5'-nucleotidase from immobilized laminin and thus enabled its isolation from other myoblast laminin-binding proteins. PMID- 2317878 TI - Lyme disease: first indigenous case in Quebec. PMID- 2317877 TI - Differential effect of pH on solubilization of nuclear lamins A/C and lamin B. AB - Extraction of isolated rat liver nuclear envelopes with 4M urea at various pH values led to differential solubilization of lamin polypeptides. All three lamins A, B and C were solubilized to 70-80% when extraction was performed at pH 8 while only 50-60% of lamins A and C were solubilized at pH 6, leaving lamin B completely insoluble. These results indicated that the interaction of lamin B with the nuclear envelope was strongly dependent upon the ionization state of lamin B and/or of its putative attachment site. PMID- 2317879 TI - Lyme disease--United States, 1987 and 1988. PMID- 2317880 TI - Influenza virus strain identification. PMID- 2317881 TI - Two outbreaks of Clostridium perfringens food poisoning-Ontario. PMID- 2317883 TI - Heightened risks for women cited in Heart and Stroke Facts. PMID- 2317882 TI - The Tennessee living will statute and its impact on the professional nurse. PMID- 2317884 TI - Effects of amiloride on metabolism and contractility during reoxygenation in perfused rat hearts. AB - Myocardial recovery after hypoxia may be determined not only by the extent of metabolic depression during the hypoxic period but also by changes in cation contents as well. Calcium overload during reoxygenation, mediated in part by Na Ca exchange and supported by the rise in cell sodium during hypoxia, may be one factor. The effects of amiloride (0.1 mM), a diuretic that inhibits Na(+)-H+ and Na-Ca exchanges in cardiac sarcolemma and mitochondria preparations, were studied during hypoxia-reoxygenation in the isovolumic, isolated rat heart. During hypoxia, cell sodium, measured using potassium ethylenediamine tetraacetate cobaltate as an extracellular marker, increased in amiloride and amiloride-free hearts, but there was no increase in cell calcium (3.3 +/- 0.3 vs. 3.6 +/- 0.9 mumol/g dry wt; p = NS). Amiloride did not alter developed pressure (DP), end diastolic pressure (EDP), pH, or integrated areas of adenosine triphosphate (ATP) and phosphocreatine (PCr) (determined by phosphorus-31-nuclear magnetic resonance spectroscopy) during hypoxia or normal perfusion conditions. Forty minutes after reoxygenation, however, cell calcium was significantly lower in the amiloride (5.1 +/- 1.3 mumol/g dry wt) than in the amiloride-free group (10.4 +/- 1.8 mumol/g dry wt; p less than 0.001), and there was improved recovery of DP (percent of initial) (72 +/- 12% vs. 41 +/- 12%; p less than 0.001), PCr (99 +/- 9% vs. 70 +/- 14%; p less than 0.001), and pH (7.17 +/- 0.17 vs. 6.88 +/- 0.16; p less than 0.001) in the amiloride group. To determine whether this dose of amiloride inhibits the manifestations of sodium-mediated calcium gain in the same model during normoxia, the metabolic and functional sequelae of lithium substituted low sodium (50 mM) perfusion were studied. Amiloride significantly limited the manifestations of sodium-mediated calcium gain as indexed (all expressed as percent of control) by a lower peak DP (221 +/- 25% vs. 284 +/- 20%) at 3 minutes, improved preservation of PCr (85 +/- 10% vs. 68 +/- 9%) and ATP (104 +/- 12% vs. 84 +/- 9%), lower rise in inorganic phosphate (201 +/- 74% vs. 332 +/- 106%), and a smaller fall in intracellular pH (7.01 +/- 0.04 vs. 6.70 +/- 0.15, p less than 0.05) for all metabolic parameters during a 20-minute period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2317885 TI - Noninvasive recovery of epicardial potentials in a realistic heart-torso geometry. Normal sinus rhythm. AB - The inverse problem in electrocardiography implies the reconstruction of electrical events within the heart from information measured noninvasively on the body surface. Deduction of these electrical events is possible from measured epicardial potentials, and, thus, a noninvasive method of recovering epicardial potentials from body surface data is useful in experimental and clinical studies. In the present study, an inverse method that uses Tikhonov regularization was shown to reconstruct, with good accuracy, important events in cardiac excitation. The inverse procedure was employed on data obtained from a human-torso tank in which a beating canine heart was placed in the correct anatomical position. Comparison with the actual, measured epicardial potentials indicates that positions and shapes of potential features (maxima, minima, zero potential line, saddles, etc.) are recovered with good accuracy throughout the QRS. An error in position of up to 1 cm is typical, while amplitudes are slightly diminished. In addition, application was extended from the above setting, in which the geometry was precisely known and potentials at a large number of leads were measured accurately, to a situation that is more representative of clinical and experimental settings. Effects of inaccuracy in location of the position of the heart were examined. A stylized torso that approximates the actual geometry was designed, and its performance in the inverse computations was evaluated. A systematic method of reduction of the number of leads on the body surface was proposed, and the resulting lead configurations were evaluated in terms of the accuracy of inverse solutions. The results indicate that the inverse problem can be stabilized with respect to different types of uncertainties in measured data and offer promise in the use of the inverse procedure in clinical and experimental situations. PMID- 2317886 TI - Thromboxane B2 in cardiac lymph. Effect of superoxide dismutase and catalase during myocardial ischemia and reperfusion. AB - Neutrophils have been implicated in the genesis of myocardial ischemia reperfusion injury, and their mechanism of action has been linked to the production of reactive oxygen species, fatty acid-derived prostanoids, and leukotrienes. In this study, we examined the potential relation between production of reactive oxygen species and cyclooxygenase-derived autacoids by studying the effects of superoxide dismutase (SOD) and catalase (CAT) on the rise in thromboxane formation observed with myocardial ischemia and reperfusion. Immunoreactive thromboxane B2 was measured in cardiac lymph from conscious dogs during reperfusion after a 60-minute occlusion in the presence of infusions of SOD alone, CAT alone, and a combination of SOD and CAT. Reperfusion after 60 minutes of ischemia causes an immediate elevation in thromboxane B2. SOD and CAT infusion prevented this rise in thromboxane B2 as did infusion of SOD alone. The ability of SOD-CAT to suppress thromboxane B2 production dissipated within 3 hours after the cessation of infusion, at which time thromboxane B2 excretion increased. The modulation of fatty acid oxygenases by reactive oxygen species may be a very important pathogenic factor in considering the origin of the protective effect of antioxidants in the setting of myocardial ischemia-reperfusion injury. PMID- 2317887 TI - Flow patterns and spatial distribution of atherosclerotic lesions in human coronary arteries. AB - To investigate the potential role of fluid mechanical factors in the localized genesis and development of atherosclerotic lesions in humans, the exact anatomic locations of atherosclerotic lesions and the flow patterns at such sites in left and right human coronary arteries were studied in detail by flow visualization and high-speed cinemicrographic techniques using five isolated, transparent human coronary arterial trees prepared postmortem. It was found that atherosclerotic plaques and wall thickenings in left and right coronary arteries were localized almost exclusively on the outer wall of one or both daughter vessels at major bifurcations and T-junctions, which left the flow-divider free of lesions, and along the inner wall of curved segments. When flow patterns in such vessels were studied in detail, it was discovered that these sites were where flow was either slow or disturbed with the formation of slow recirculation and secondary flows and where wall shear stress was low. The results indicate that the major hemodynamic factors directly related to the localization of atherosclerotic plaques and wall thickenings in the human arterial system are the low fluid velocity and the resultant low shear stress that acts on the vessel wall. PMID- 2317888 TI - Importance of the great vessels in the genesis of the electrocardiogram. AB - The electrocardiogram is the graphic representation against time of the difference in potential between points of the body caused by the current field of the heart. To examine the origin of this current field, a method of transforming body surface electrocardiographic data to the epicardial surface has been developed. The computed epicardial current density distributions in 219 patients with acute inferior myocardial infarction showed that, in 89% of patients, the current flow out of the heart during the ST segment came from two regions, not only from the infarction region but also from a region over the great vessels. This findings suggests that current flows from the ischemic region, through the low-resistance pathway provided by the intracavity blood, out the great vessels, and back to the epicardium. A similar pathway has been hypothesized when ischemia caused endocardial ST elevation, such as during a stress test or with unstable angina. To test this hypothesis, a group of patients with ST depression on the 12 lead electrocardiogram, not associated with ST elevation, was examined with body surface mapping. Ninety-four percent of patients had epicardial current density distributions that showed a region of current flow out of the heart and over the great vessels that was consistent with this hypothesis. This could explain the poor localization of coronary artery disease by electrocardiographic techniques when there is ST depression on the body surface. PMID- 2317889 TI - Vascular reactivity during the progression of atherosclerotic plaque. A study in Watanabe heritable hyperlipidemic rabbits. AB - The effects of varying degrees of atherosclerotic plaque on vascular responsiveness in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits and New Zealand White (normal cholesterolemic) rabbits were studied. Ring segments from the aortic arch and thoracic aorta were mounted in organ chambers for isometric tension recording and measurement of endothelium-derived relaxing factor. WHHL rabbits were divided into three groups according to age: group 1, 3 5 months; group 2, 6-9 months; and group 3, 12-14 months. Atherosclerotic changes (expressed as a percent of total surface area) in the aortic arches in groups 1, 2, and 3 were 11 +/- 3% (mild), 28 +/- 6% (moderate), and 54 +/- 8% (severe) respectively; only occasional plaques were present in the thoracic aorta in all groups. Maximal contractions elicited with phenylephrine progressively decreased with increasing degrees of atherosclerotic plaque. Contractions evoked by histamine were augmented in all groups of WHHL rabbits when compared with controls, whereas those to serotonin were augmented only in vessels with mild atherosclerosis. As the severity of the intimal lesions increased, endothelium dependent relaxations to acetylcholine, ATP, and calcium ionophore A23187 progressively decreased. Endothelium-independent relaxation to nitroglycerin was virtually complete in all segments. However, vessels with severe atherosclerosis were less sensitive to this agent as illustrated by a significant increase in the ED50 value. Scanning electron microscopy revealed a predominant loss of endothelial cells in the central regions of fibrous plaques. Thus, in WHHL rabbits, hypercholesterolemia and atherosclerosis result in an increased responsiveness of vascular smooth muscle to histamine and serotonin. Endothelium mediated relaxation of vascular smooth muscle is reduced with the progression of atherosclerosis primarily due to a loss of endothelial cells. PMID- 2317890 TI - Ischemic preconditioning reduces infarct size in swine myocardium. AB - We evaluated the hypothesis that stunning swine myocardium with brief ischemia reduces oxygen demand in the stunned region and increases tolerance of myocardium to longer periods of ischemia. Wall function was quantified with ultrasonic crystals aligned to measure wall thickening, and stunning was achieved with two cycles of left anterior descending coronary artery (LAD) occlusion (10 minutes) and reperfusion (30 minutes), after which the LAD was occluded for 60 minutes and reperfused for 90 minutes. Infarct size (as a percent of risk region) was then determined by incubating myocardium with para-nitro blue tetrazolium. Regional oxygen demand was measured as myocardial oxygen consumption before the 60-minute LAD occlusion in the stunned region; tracer microspheres were used to determine blood flow, and blood from the anterior interventricular vein and left atrium was used to calculate oxygen saturations. After the second reperfusion period, wall thickening in the stunned region was reduced to 1.4 +/- 2.4% compared with 36.7 +/- 2.5% (mean +/- SEM) before ischemia (p less than 0.001). Regional myocardial oxygen consumption after stunning (3.1 +/- 0.7 ml O2/min/100 g) was no different from regional myocardial oxygen consumption before stunning (3.7 +/- 0.6 ml O2/min/100 g). In the nine pigs "preconditioned" by stunning, infarct size was 10.4 +/- 6.3% of the risk region compared with 48.0 +/- 12.7% in the six control pigs subjected to 60 minutes of ischemia without prior stunning (p less than 0.005). The risk regions were similar (14.4 +/- 1.5% vs. 14.6 +/- 1.9% of the left ventricle, preconditioned vs. control pigs, respectively). We conclude that stunning swine myocardium with two cycles of a 10-minute LAD occlusion followed by reperfusion increases ischemic tolerance but that changes in regional demand in stunned myocardium do not predict the marked reduction in infarct size that follows a subsequent 60-minute period of ischemia. PMID- 2317891 TI - Phorbol ester and dioctanoylglycerol stimulate membrane association of protein kinase C and have a negative inotropic effect mediated by changes in cytosolic Ca2+ in adult rat cardiac myocytes. AB - We used left ventricular myocytes from adult rats to investigate the effect of 4 beta-phorbol 12-myristate 13-acetate (PMA) and of sn-1,2-dioctanoylglycerol (DiC 8) on the membrane association of protein kinase C (PKC), cytosolic [Ca2+], (Cai) homeostasis, and the contractile properties of single cardiac cells. Because PKC activity is known to be highly Ca2+ sensitive, the K+ concentration of the bathing medium was raised from 5 to 30 mM in some experiments, a perturbation known to depolarize the cell and increase Cai. In cell suspensions both PMA (3 x 10(-10) and 3 x 10(-7) M) and DiC-8 (10(-5) and 10(-4) M) increased membrane association of PKC. The effect of PMA (10(-7) M) on PKC translocation was enhanced in 30 mM KCl compared with 5 mM KCl. During steady field stimulation at 1 Hz in 1 mM bathing [Ca2+], both PMA (10(-7) M) and DiC-8 (10(-5) M) decreased twitch amplitude to approximately 60% of control in 5 mM KCl, and the negative inotropic effect of either drug was more pronounced in 30 mM KCl than in 5 mM KCl. In single cardiac myocytes loaded with the Ca2+ indicator indo-1 and bathed in 5 mM KCl, we simultaneously measured cell length and Cai. The myofilament responsiveness to Ca2+ was assessed by the relation between contraction amplitude and the peak of the Cai transient. The negative inotropic effect of both PMA and DiC-8 was related to a diminished amplitude of the Cai transient and not to a decreased myofilament responsiveness to Ca2+. In the absence of electrical stimulation, PMA (10(-7) M) and DiC-8 (10(-5) M) decreased the frequency of contractile waves due to spontaneous Ca2+ release from the sarcoplasmic reticulum, and DiC-8 also decreased resting Cai. Thus, activation of PKC, which is thought to occur as part of the response of cardiac muscle to alpha 1 adrenergic stimulation, is associated with a negative inotropic action due to a smaller Cai transient rather than to a decrease in the myofilament responsiveness to Ca2+. These effects on the membrane association of PKC and on contractility are enhanced by cell depolarization achieved by raising [KCl] in the bathing medium. PMID- 2317892 TI - Detection of oxygen-derived free radical generation in the canine postischemic heart during late phase of reperfusion. AB - To define the relation between oxygen-derived free radical (oxy-radical) generation in the reperfused ischemic myocardium and the progression of myocardial damage, we measured oxy-radical generation in the ischemic myocardium and the propagating infarct size in a model of canine coronary occlusion (90 minutes) and reperfusion. We used electron paramagnetic resonance spin-trapping techniques (5,5-dimethyl-1-pyrroline N-oxide [DMPO]) to detect oxy-radicals in the rapidly frozen myocardial samples taken by needle biopsy. There was no detectable generation of DMPO adducts in the normal myocardium before or after reperfusion. In the reperfused ischemic myocardium, electron paramagnetic resonance signals of DMPO-OOH (superoxide anion) and DMPO-OH (hydroxyl radical) were detected, with peak concentrations at 1 hour after reperfusion for DMPO-OOH and at 3 hours after reperfusion for DMPO-OH, respectively. These DMPO adducts were also detected during the early phase (15 seconds) of reperfusion, but the concentrations of these signals were much less than those during the late phase of reperfusion. Treatment with human recombinant superoxide dismutase (2.5 mg/kg/hr) and catalase (2.5 mg/kg/hr) during the course of experiments abolished DMPO-OOH formation but had little effect on DMPO-OH formation. Infarct size (percent of risk area infarcted), quantified by a dual staining method with Evans blue dye and triphenyltetrazolium chloride, was 18.3 +/- 4.8% (mean +/- SEM) at 90 minutes of occlusion. After 5 hours of reperfusion, infarct size increased to 43.6 +/- 7.2%. These results indicate that a greater magnitude of oxy-radical generation was sustained in the ischemic myocardial tissue during the late phase (1-3 hours) of reperfusion, associated with the progression of myocardial infarction. The concurrent appearance of oxy-radicals and progressive infarction may support the view that a chain reaction of oxy-radicals contributes to the propagation of myocardial cell damage in the postischemic heart. PMID- 2317893 TI - Acceleration of platelet aggregability due to modulation of native LDL. AB - The aim of this experiment was to clarify whether low density lipoprotein (LDL) causes an acceleration of platelet aggregability. Native LDL was separated into two fractions by filtered tap-water dialysis, namely, water-soluble LDL (WS-LDL) and non-water-soluble LDL. Although native LDL did not enhance the platelet aggregability, WS-LDL made it markedly increased. WS-LDL consisted of the lipid constituents that were not found in native LDL. Namely, in thin-layer chromatography of WS-LDL, an unknown spot between triolein and free fatty acid was clearly stained. This unknown spot in the WS-LDL was produced by the peroxidation of cholesteryl ester in native LDL. It was confirmed that the spot has the same Rf value as the peroxidate of cholesteryl linolate in thin-layer chromatography. If native LDL is modulated by divalent metal ions and oxygen in the fluids, LDL with biological activity such as an increase of platelet aggregability is produced. PMID- 2317894 TI - Immunohistochemical demonstration of human cardiac innervation before and after transplantation. AB - Knowledge about the distribution and origins of peptide-containing nerves in the innervated and transplanted heart is lacking. Immunohistochemical and histochemical techniques were used to visualize human cardiac innervation before and after transplantation. In the recipient heart cardiac nerve fibers and fascicles displayed immunoreactivity for general neural (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). A major proportion of cardiac nerves displayed neuropeptide tyrosine and tyrosine hydroxylase immunofluorescence staining. Subpopulations of nerves contained somatostatin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P- or neurokinin-like immunoreactivity, and acetylcholinesterase activity. Tissues from cardiac allografts (5 weeks to 63 months after transplantation) contained nerves and ganglion cells that were acetylcholinesterase positive and immunoreactive for the general neural markers. These nerves were less numerous than in recipient hearts and rarely displayed neuropeptide immunostaining. Atrial natriuretic peptide immunoreactivity was localized to myocardial cells in transplanted hearts as well as explanted recipient and postmortem hearts. While most human cardiac allografts remain functionally extrinsically denervated, they appear to contain viable intrinsic nerves, and myocardial cells retain the capacity to produce atrial natriuretic peptide. PMID- 2317895 TI - Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. AB - We have shown previously that preconditioning myocardium with four 5-minute episodes of ischemia and reperfusion dramatically limited the size of infarcts caused by a subsequent 40-minute episode of sustained ischemia. The current study was undertaken to assess whether the same preconditioning protocol slowed the loss of high energy phosphates, limited catabolite accumulation, and/or delayed ultrastructural damage during a sustained ischemic episode. Myocardial metabolites and ultrastructure in the severely ischemic subendocardial regions were compared between control and preconditioned canine hearts. Hearts (four to 10 per group) were excised after 0, 5, 10, 20, or 40 minutes of sustained ischemia. All groups had comparable collateral blood flow. Preconditioned hearts developed ultrastructural injury more slowly than controls; evidence of irreversible injury was observed after 20 minutes in controls but not until 40 minutes in preconditioned hearts. Furthermore, after 40 minutes of ischemia, irreversible injury was homogeneous in controls but only focal in preconditioned myocardium. Preconditioning reduced starting levels of ATP by 29%. Nevertheless, it also slowed the rate of ATP depletion during the episode of sustained ischemia, so that after 10 minutes of ischemia, preconditioned hearts had more ATP than controls. However, after 40 minutes, ATP contents were not significantly different between groups. Preservation of ATP resulted from reduced ATP utilization and was not due to increased ATP production. Accumulation of purine nucleosides and bases (products of adenine nucleotide degradation) was limited in preconditioned myocardium. Accumulation of glucose-1-phosphate, glucose-6 phosphate, and lactate also was reduced markedly by preconditioning, due to reduced rates of glycogen breakdown and and anaerobic glycolysis. We propose that preconditioning reduces myocardial energy demand during ischemia, which results in a reduced rate of high energy phosphate utilization and a reduced rate of anaerobic glycolysis. Either preservation of ATP or reduction of the cellular load of catabolites may be responsible for delaying ischemic cell death. PMID- 2317896 TI - Effect of wall shear rate on thrombogenesis in microvessels of the rat mesentery. AB - The role of hemodynamics on platelet thrombus formation was studied in venules and arterioles of the rat mesentery. Thrombus formation was induced by the fluorescent dye/light method for examination of the following factors: 1) the effect of wall shear rate on thrombus initiation, 2) the effect of wall shear rate on the growth of thrombi, and 3) the relation between platelet thrombus initiation and intraluminal velocity profile. The range of wall shear rate was up to approximately 1,000 1/sec in venules and from 640 to 2,900 1/sec in arterioles. Platelet thrombus initiation occurred more rapidly at higher wall shear rate in venules and at lower wall shear rate in arterioles. Thrombus initiation time was shortest around a wall shear rate of 900 1/sec in venules and around 700 1/sec in arterioles. Thrombus growth rate in venules was greatest at a wall shear rate of 1,500-2,000 1/sec. Thrombus initiation and its relation to blood flow was also examined in branched and curved microvessels. In these vessels platelet thrombi were also first initiated at the sites of higher wall shear rate in venules and of lower wall shear rate in arterioles. PMID- 2317897 TI - Collagen and elastin metabolism in hypertensive pulmonary arteries of rats. AB - We evaluated the processes controlling the accumulation of collagen and elastin in main pulmonary arteries of rats during an episode of hypoxic pulmonary hypertension. Explant cultures of main pulmonary arteries were incubated with [3H]proline to measure collagen and protein synthesis and percent collagen synthesis. Elastin synthesis was measured by [14C]valine incorporation into insoluble elastin. Relative collagen synthesis increased twofold (from 1.1 +/- 0.2 x 10(3) to 2.0 +/- 1.0 x 10(3) disintegrations per minute [14C]hydroxyproline/vessel/hr/mg protein), relative collagen synthesis doubled (from 2% to 4-5% of total protein synthesis), and elastin synthesis increased ninefold (from 0.4 +/- 0.2 x 10(4) to 3.6 +/- 0.6 x 10(4) dpm [14C]valine/vessel/hr/mg protein) in early hypertension. The level of pro alpha l(I) collagen RNA paralleled the relative collagen synthetic rate during the study period. Within 7 days of recovery from hypoxia, collagen and elastin contents were normal. We conclude that collagen and elastin in main pulmonary arteries are synthesized rapidly during an episode of hypoxic pulmonary hypertension and that collagen and elastin are rapidly removed from the hypertensive vessel during normoxic recovery. PMID- 2317898 TI - Molecular cloning of gene sequences from rat heart rapidly responsive to pressure overload. AB - Although pressure overload induces cardiac hypertrophy and reexpression of contractile protein isogenes, the molecular mechanism of both is not well understood. We demonstrated the early change in the translational activity of specific cardiac messenger RNA by two-dimensional gel electrophoresis of in vitro translational products. A total of over 400 translational products were detected by fluorography, and the relative predominance of eight species was increased by pressure overload whereas that of two translational products was decreased. We cloned four pressure-overload-responsive complementary DNA clones, pPO-1, -4, -5, and -6, by differential dot blot hybridization. Two clones were increased from the early period after the imposition of pressure overload; the other two were decreased. The expression pattern of each complementary DNA clone in the pressure overloaded hearts was similar to that in fetal hearts. Pressure overload also induced the additional messenger RNA, which hybridized with pPO-4. This mRNA was also recognized in fetal, neonatal, and adult spontaneously hypertensive rat hearts. The induction of this transcript by pressure overload was not suppressed but, rather, stimulated by cycloheximide. These results suggest that there are some genes that rapidly respond to pressure overload and that may play some role in the development of cardiac hypertrophy. PMID- 2317899 TI - Decreased contractile efficiency and increased nonmechanical energy cost in hyperthyroid rabbit heart. Relation between O2 consumption and systolic pressure volume area or force-time integral. AB - Both systolic pressure-volume area (PVA) and force-time integral (FTI) have been used as measures of oxygen consumption per beat (VO2) in the isolated left ventricle. The reciprocal of the slope of the VO2-PVA relation has been considered to reflect the chemomechanical energy transduction efficiency of the contractile machinery (contractile efficiency), whereas its VO2 intercept consists of energy cost of excitation-contraction coupling and basal metabolism. To examine whether the increase in myosin isoform V1/V3 ratio in hyperthyroid rabbits decreases contractile efficiency and to determine overall mechanisms of higher oxygen consumption in hyperthyroid hearts, the VO2-PVA and VO2-FTI relations as well as the end-systolic pressure-volume relation were assessed in cross-circulated, isovolumically beating hearts isolated from normal, hyperthyroid, and hypothyroid rabbits. Normalized initial slopes of the rising limb of the curvilinearly fitted end-systolic pressure-volume relation (E'max, ventricular contractility index) were similar for normal and hyperthyroid groups. However, the slopes and VO2 intercepts of the VO2-PVA and VO2-FTI relations were greater in hyperthyroid hearts than in normal hearts. Accordingly, in the hyperthyroid hearts, the contractile efficiency (27 +/- 6%) was lower and left ventricular VO2 for excitation-contraction coupling (0.028 +/- 0.004 ml O2/beat/100 g) was higher than in normal hearts (40 +/- 4% and 0.021 +/- 0.005 ml O2/beat/100 g, respectively). This decreased contractile efficiency in the hyperthyroid hearts was attributable to myosin isoform alteration rather than to increased beta-adrenoceptors because isoproterenol did not affect the slope of the VO2-PVA relation in all groups. In contrast, the slope of the VO2-FTI relation was significantly increased by isoproterenol in all groups. Neither the VO2-PVA nor the VO2-FTI relations in hypothyroid hearts were different from those in normal hearts except for significantly lower VO2 for basal metabolism. We conclude that in hyperthyroid rabbits, the left ventricle has decreased contractile efficiency and increased energy cost of excitation-contraction coupling and that the decreased contractile efficiency in hyperthyroid hearts is probably due to the increased V1/V3 ratio of the myosin isoform component. In addition, this study demonstrates that the VO2-PVA and VO2-FTI relations dissociate depending on the intervention, even in the same isovolumic contraction mode. PMID- 2317900 TI - Determinants of survival and left ventricular performance after mitral valve replacement. Department of Veterans Affairs Cooperative Study on Valvular Heart Disease. AB - To determine how survival and clinical status were related to left ventricular (LV) size and systolic function after mitral valve replacement, 104 patients (48 mitral regurgitation [MR], 33 mitral stenosis [MS], and 23 MS/MR) with isolated mitral valve replacement were evaluated before and after surgery. Preoperative hemodynamic abnormalities by cardiac catheterization were improved 6 months after surgery in all three patient groups. The patients with MR exhibited reductions in LV end-diastolic volume index (EDVI) (117 +/- 51 to 89 +/- 27 ml/m2, p less than 0.001) and ejection fraction (EF) (0.56 +/- 0.15 to 0.45 +/- 0.13, p less than 0.001); however, the ratio of forward stroke volume to end-diastolic volume increased (0.32 +/- 0.21 to 0.45 +/- 0.17, p less than 0.001) because of the elimination of regurgitant volume. Survival analysis revealed that mortality was significantly higher in MS or MS/MR patients with postoperative EDVI more than 101 ml/m2 (p less than 0.001 and p less than 0.042, respectively) and in MR patients with postoperative EF less than or equal to 0.50 (p less than 0.031). Also, the majority of patients with MR or MS/MR and postoperative EDVI more than 101 ml/m2 and EF less than or equal to 0.50 were in New York Heart Association class III or IV. Multivariate logistic regression analysis in the patients with MR revealed that the strongest predictor of postoperative EF was preoperative EF (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317901 TI - 111In platelet imaging of left ventricular thrombi. Predictive value for systemic emboli. AB - To determine whether a positive indium 111 platelet image for a left ventricular thrombus, which indicates ongoing thrombogenic activity, predicts an increased risk of systemic embolization, we compared the embolic rate in 34 patients with positive 111In platelet images with that in 69 patients with negative images during a mean follow-up of 38 +/- 31 (+/- SD) months after platelet imaging. The positive and negative image groups were similar with respect to age (59 +/- 11 vs. 62 +/- 10 years), prevalence of previous infarction (94% vs. 78%, p less than 0.05), time from last infarction (28 +/- 51 vs. 33 +/- 47 months), ejection fraction (29 +/- 14 vs. 33 +/- 14), long-term or paroxysmal atrial fibrillation (15% vs. 26%), warfarin therapy during follow-up (26% vs. 20%), platelet inhibitory therapy during follow-up (50% vs. 33%), injected 111In dose (330 +/- 92 vs. 344 +/- 118 microCi), and latest imaging time (greater than or equal to 48 hours in all patients). During follow-up, embolic events occurred in 21% (seven of 34) of patients with positive platelet images for left ventricular thrombi as compared with 3% (two of 69) of patients with negative images (p = 0.002). By actuarial methods, at 42 months after platelet imaging, only 86% of patients with positive images were embolus free as compared with 98% of patients with negative images (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317902 TI - Left-to-right atrial shunting after percutaneous mitral valvuloplasty. Incidence and long-term hemodynamic follow-up. AB - To assess the incidence and long-term evolution of left-to-right atrial shunting (AS) after the performance of percutaneous mitral valvuloplasty (PMV), venovenous indicator dilution curves and right heart oximetric measurements were obtained in 68 consecutive patients before and after successful PMV. The procedure increased the mitral valve area (p less than 0.0001) and decreased the mitral gradient (p less than 0.0001). No AS was detected before PMV, but it was detected immediately after PMV. Oximetry identified AS in 17 patients (25%), and dilution curves identified AS in an additional 25 (total, 62%). The ratio of mean pulmonary to systemic blood flow (Qp/Qs) was 1.31 +/- 0.2, and in six patients (9%), the ratio was 1.5 or greater. Among nine clinical, 20 hemodynamic, and six procedural variables, stepwise logistic regression analysis selected the following as independent predictors of AS: smaller increases in valve area (p = 0.01) after PMV, absence of previous surgical commissurotomy (p = 0.02), mitral valve calcification (p = 0.02), and smaller left atria (p = 0.06). Among the 33 patients recatheterized at 6 months, oximetry had detected AS in 10, and dilution curves detected AS in an additional nine (total, 58%) immediately after PMV. At 6 months, AS had decreased or disappeared in 14 of these patients (74%), had increased in three (16%), and was unchanged in two (10%). Overall, at 6 months, oximetry identified AS in three patients, and dilution curves identified AS in an additional 13 (total, 48%). AS was detected at 6 months in only three patients but was not detected immediately after PMV. Although AS is very frequent immediately after PMV, Qp/Qs is usually less than 1.5. The appearance of shunting correlates with patient characteristics and with less improvement in valve area after PMV. Atrial shunting usually persists at 6 months, but its severity almost always decreases. PMID- 2317903 TI - Reversible segmental left ventricular dysfunction after coronary angioplasty. AB - Patients with chronic segmental myocardial dysfunction may demonstrate improvement after coronary revascularization. To evaluate the early effects of percutaneous transluminal coronary angioplasty (PTCA) on resting left ventricular segmental function, we obtained serial two-dimensional echocardiograms 1.1 +/- 0.9 days before and 3.1 +/- 2 days after elective PTCA in 40 patients. Echocardiograms were reviewed in a blind fashion; left ventricular segmental wall motion was analyzed in four short-axis views, and a score was assigned to each region (0, normal; 1, hypokinetic; and 2, akinetic). Abnormal regional wall motion was present in 20 of the patients before PTCA. Summed segment scores in these 20 patients showed an improvement in regional wall motion from 4.5 +/- 2.5 to 1.6 +/- 2.1 (p less than 0.01) after successful PTCA. Similar results were obtained when the patients were divided into those with or without a previous myocardial infarction. Improvement occurred in the seven patients without a previous myocardial infarction; the summed segment score decreased from 4.2 +/- 3.4 to 0.86 +/- 1.6 (p less than 0.05) after PTCA. Ten of the 13 patients with a prior myocardial infarction demonstrated improvement in wall motion after PTCA; the summed segment scores decreased 54% (p less than 0.001). Of the 260 segments analyzed in the study, 180 were normal before and after PTCA. Forty-nine of the 69 hypokinetic segments were normal, and 10 of 12 akinetic segments were hypokinetic after successful coronary revascularization. There was no deterioration in wall motion after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317904 TI - Decreased magnitude of heart rate spectral components in coronary artery disease. Its relation to angiographic severity. AB - We analyzed the spectral components of RR interval variability under controlled respiration (15 breaths/min) in 56 patients (age range, 35-73 years) referred for coronary angiography; 14 patients had multivessel disease (group M), 21 had one vessel disease (group S), and 21 had nonsignificant disease or normal coronary artery (group N). There were 43 healthy controls (age range, 36-71 years) (group C). The patients had no clinical evidence of heart failure, hypertension, diabetes mellitus, or acute stage of infarction and had taken no medication for 3 days. The autoregressive power spectral density of RR interval variability contains two major components, respiratory sinus arrhythmia (RSA) (0.25 Hz) and Mayer wave-like sinus arrhythmia (MWSA) (0.04-0.15 Hz), which have magnitudes that are quantitative markers of cardiac vagal activity and sympathetic activity with vagal modulation, respectively. We represented the magnitudes by the coefficient of component variance (CCV), which provided the amplitude relative to the mean RR interval. The age- and sex-adjusted mean of CCVRSA significantly decreased with advancing angiographic severity (1.64 +/- 0.09%, 1.66 +/- 0.12%, 1.22 +/- 0.13%, and 0.81 +/- 0.16% for groups C, N, S, and M, respectively) (p = 0.0001). The CCVRSA was unrelated to left ventricular function, previous myocardial infarction, or stenosis of any specific artery including the sinoatrial and atrioventricular node arteries. The CCVMWSA decreased only in group M (p = 0.0462). These results indicate that coronary artery disease is associated with vagal dominant impairment in autonomic cardiac function and that reduction in the vagal cardiac function correlates with the angiographic severity. PMID- 2317905 TI - Effect of intravenous propranolol on coronary vasomotion at rest and during dynamic exercise in patients with coronary artery disease. AB - Coronary vasomotion was studied at rest and during bicycle exercise with biplane quantitative coronary arteriography in 28 patients with coronary artery disease. Patients were divided into two groups; the first 18 patients served as controls (group 1), and the next 10 patients were treated with propranolol 0.1 mg/kg, which was infused intravenously before exercise (group 2). Luminal area of a normal and a stenotic vessel segment was determined at rest, during supine bicycle exercise, and 5 minutes after sublingual administration of 1.6 mg nitroglycerin after exercise. In group 1, the normal vessel showed vasodilation (+16%, p less than 0.001) during exercise, whereas the stenotic vessel segment showed vasoconstriction (-31%, p less than 0.001). After sublingual administration of nitroglycerin, there was coronary vasodilation of both normal (+36%, p less than 0.001 vs. rest) and stenotic (+20%, p less than 0.001) vessel segments. Patients with angina pectoris during supine exercise (n = 10) had significantly (p less than 0.05) more vasoconstriction (-36%) than patients without angina (-23%). In group 2, intravenous administration of propranolol at rest was associated with a decrease in luminal area of both normal (-24%, p less than 0.001) and stenotic (-43%, p less than 0.001) vessel segments; however, during subsequent exercise, both normal (-2%, p = NS vs. rest) and stenotic (-3%, p = NS vs. rest) vessel segments dilated when compared with the measurements after propranolol. Administration of nitroglycerin further increased luminal area of both vessel segments (normal segment, +23%, p less than 0.001; stenotic segment, +46%, p less than 0.001 vs. rest). It is concluded that dynamic exercise in patients with coronary artery disease is associated with coronary vasodilation of the normal and vasoconstriction of the stenotic coronary arteries. Patients with exercise-induced angina had significantly more stenosis vasoconstriction than patients without angina although minimal luminal area at rest was similar. Intravenous administration of propranolol is accompanied by a significant decrease in coronary luminal area of both normal and stenotic vessel segments at rest, which is overridden by dynamic exercise and sublingual nitroglycerin. The reduction in myocardial oxygen consumption and the prevention of exercise-induced stenosis vasoconstriction might explain the beneficial effect of beta-blocker treatment in most patients with coronary artery disease. PMID- 2317906 TI - Noninvasive quantification of left ventricular rotational deformation in normal humans using magnetic resonance imaging myocardial tagging. AB - It has been postulated that rotation of the left ventricular apex with respect to the base is a component of normal systolic function in humans, but it has been difficult to measure it noninvasively. Tagging is a new magnetic resonance imaging technique that labels specific areas of myocardium by selective radio frequency excitation of narrow planes orthogonal to the imaging plane before acquiring an image. Tags appear as black lines and persist in myocardium for 400 500 msec and, if applied at end diastole, will move with the myocardium through systole. Tagging was used to noninvasively quantify left ventricular torsion and circumferential-longitudinal shear (shearCL) in humans. Eight normal volunteers, aged 24-38 years, were imaged in a 0.38-T iron-core resistive magnet. Five short axis left ventricular images, positioned to encompass the entire left ventricle (LV), were obtained separately at end systole. Four equiangular radial tags had been applied at end diastole, intersecting the myocardium at eight locations. We calculated the difference in angular displacement of each epicardial and endocardial tag point (a tag point being where the tag crossed the epicardium or endocardium) at end systole from the systolic position of the corresponding tag point on the basal plane. This value was called the torsion angle. From this, shearCL, the angle inscribed on the epicardial or endocardial surface between the systolic tag position, the corresponding basal tag position, and its projection onto the slice of interest could be calculated at 32 points in the left ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317907 TI - Transvenous defibrillation in humans via the coronary sinus. AB - A consistently effective transvenous defibrillation system for use in automatic defibrillators could significantly alter the approach to patients at risk of sudden death. Transvenous defibrillation systems that use a right ventricular (RV) electrode only or an RV electrode in combination with a chest patch are relatively inefficient at applying current to the posterolateral left ventricle. An RV electrode combined with a coronary sinus (CS) electrode, however, may improve current distribution to the posterolateral left ventricle. The purpose of this investigation, therefore, was to evaluate the effectiveness and safety of a specially designed transvenous lead system with a CS electrode capable of current delivery to this relatively inaccessible region of the heart. In 20 survivors of cardiac arrest, we determined defibrillation efficacy immediately before defibrillator surgery for monophasic pulses delivered between an RV catheter electrode and a CS catheter electrode system and compared these findings with an RV catheter electrode-thoracic patch defibrillation system. Subsequently, we referenced the efficacy of both transvenous systems to an epicardial patch electrode system at the time of defibrillator implantation. The mean delivered energy defibrillation threshold for the CS-RV electrode system was 17.5 +/- 7.9 J, which was substantially lower than the RV electrode-thoracic patch system (25.6 +/- 11.4 J, p = 0.0016 [46% more]). Defibrillation threshold voltage was 529 +/- 123 V for the CS-RV electrode system and 647 +/- 164 V (22% more) for the RV electrode-thoracic patch system (p = 0.0013).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317908 TI - Detection of left main coronary artery stenosis by transesophageal color Doppler and two-dimensional echocardiography. AB - Although transthoracic two-dimensional echocardiography can detect dilation of the coronary arteries, the reliability of this technique in the detection of coronary artery stenosis is still doubtful. The purpose of this study was to test the ability of newly developed biplane transesophageal color Doppler and two dimensional echocardiography in the detection of left main coronary artery stenosis. Blood flow in the left main coronary artery was detected in 57 of 67 (85%) patients by transesophageal color Doppler flow imaging. Using transesophageal two-dimensional echocardiography, adequate images of the full length of the left main coronary artery and identification of the bifurcation were obtained in 60 of 67 (90%) patients. Transesophageal echocardiography clearly showed significant (greater than or equal to 50%) narrowing of the coronary lumen in 10 of 11 patients (sensitivity, 91%) and insignificant narrowing or no abnormalities of the coronary lumen in the other 49 patients (specificity, 100%). The positive predictive accuracy for left main coronary artery disease was 100%, and the negative predictive accuracy was 98%. This preliminary study suggests that biplane transesophageal color Doppler and two dimensional echocardiography appears to be a feasible noninvasive technique for imaging the left main coronary artery and detecting hemodynamically significant luminal obstruction. PMID- 2317909 TI - Dissociation of end systole from end ejection in patients with long-term mitral regurgitation. AB - To determine whether left ventricular (LV) end systole and end ejection uncouple in patients with long-term mitral regurgitation, 59 patients (22 control patients with atypical chest pain, 21 patients with aortic regurgitation, and 16 patients with mitral regurgitation) were studied with micromanometer LV catheters and radionuclide angiograms. End systole was defined as the time of occurrence (Tmax) of the maximum time-varying elastance (Emax), and end ejection was defined as the time of occurrence of minimum ventricular volume (minV) and zero systolic flow as approximated by the aortic dicrotic notch (Aodi). The temporal relation between end systole and end ejection in the control patients was Tmax (331 +/- 42 [SD] msec), minV (336 +/- 36 msec), and then, zero systolic flow (355 +/- 23 msec). This temporal relation was maintained in the patients with aortic regurgitation. In contrast, in the patients with mitral regurgitation, the temporal relation was Tmax (266 +/- 49 msec), zero systolic flow (310 +/- 37 msec, p less than 0.01 vs. Tmax), and then, minV (355 +/- 37 msec, p less than 0.001 vs. Tmax and p less than 0.01 vs. Aodi). Additionally, the average Tmax occurred earlier in the patients with mitral regurgitation than in the control patients and patients with aortic regurgitation (p less than 0.01, for both), whereas the average time to minimum ventricular volume was similar in all three patient groups. Moreover, the average time to zero systolic flow also occurred earlier in the patients with mitral regurgitation than in the control patients (p less than 0.01) and patients with aortic regurgitation (p less than 0.05). Because of the dissociation of end systole from minimum ventricular volume in the patients with mitral regurgitation, the end-ejection pressure-volume relations calculated at minimum ventricular volume did not correlate (r = -0.09), whereas those calculated at zero systolic flow did correlate (r = 0.88) with the Emax slope values. We conclude that end ejection, defined as minimum ventricular volume, dissociates from end systole in patients with mitral regurgitation because of the shortened time to LV end systole in association with preservation of the time to LV end ejection due to the low impedance to ejection presented by the left atrium. Therefore, pressure-volume relations calculated at minimum ventricular volume might not be useful for assessing LV chamber performance in some patients with mitral regurgitation. PMID- 2317910 TI - Exercise performance after repair of anomalous origin of the left coronary artery from the pulmonary artery. AB - Eleven patients underwent exercise testing after operative repair of anomalous origin of the left coronary artery from the pulmonary artery. Five patients repaired after 2 years of age comprised a childhood surgery group, and six patients repaired before 2 years of age comprised an infant surgery group. All patients were exercised using either a treadmill or electronically braked bicycle with simultaneous thallium 201 scintigraphy. Oxygen consumption, carbon dioxide production, pulmonary functions, and electrocardiogram were all monitored continuously. Pulmonary reserve was normal in all patients. Based on heart rate reserve, respiratory exchange ratio, and oxygen-consumption response to work load, two patients in the infant surgery group stopped exercise before achieving maximum aerobic capacity. All remaining patients achieved their maximum aerobic capacity. There was no difference in work rate or oxygen consumption during exercise between the infant and childhood surgical group. Four patients (two in each surgical group) had an impaired chronotropic response to exercise. Three of these four patients demonstrated perfusion defects by thallium scintigraphy. Thallium scintigraphy was normal in all remaining patients. Electrocardiographic abnormalities were noted in seven of 11 patients having ventricular arrhythmias or ST segment depression. It is concluded from this study that exercise performance after repair of anomalous origin of the left coronary artery from the pulmonary artery is not affected by the age at which surgery is performed. Exercise is frequently associated with electrocardiographic evidence of abnormal myocardial perfusion despite frequently negative simultaneous 201Tl scintigraphy. PMID- 2317911 TI - Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men. AB - We studied separately the effects of weight loss by calorie restriction (dieting) and by calorie expenditure (primarily, running) on lipoprotein subfraction concentrations in sedentary, moderately overweight men assigned at random into three groups as follows: exercise without calorie restriction (n = 46), calorie restriction without exercise (n = 42), and control (n = 42). Plasma lipoprotein mass concentrations were measured by analytic ultracentrifugation for flotation rates (F0(1.20), S0f) within high density lipoprotein (HDL) (F0(1.20) 0-9), low density lipoprotein (LDL) (S0f 0-12), intermediate density lipoprotein (IDL) (S0f 12-20), and very low density lipoprotein (VLDL) (S0f 20-400) particle distributions. Particle diameter and flotation rate of the most abundant LDL species were determined by nondenaturing polyacrylamide gradient gel electrophoresis and analytic ultracentrifugation, respectively. During the 1-year trial, the exercisers ran (mean +/- SD) 15.6 +/- 9.1 km/wk, and the dieters ate 340 +/- 71 fewer kilocalories per day than at baseline. Total body weight was reduced significantly more in dieters (-7.2 +/- 4.1 kg) and exercisers (-4.0 +/- 3.9 kg) than controls (0.6 +/- 3.7 kg). As compared with mean changes in controls, the exercisers and dieters significantly increased HDL2 mass (48.6% and 47.1%, respectively), decreased VLDL mass (-23.9% and -25.5%), and increased LDL peak particle diameter (2.4 and 3.2 A). When adjusted to an equivalent change in body mass index by analysis of covariance, 1) exercise-induced and diet-induced weight loss produced comparable mean changes in the mass of small LDL and VLDL, and in LDL peak particle diameter; 2) the exercisers versus control group difference in HDL2 was attributed to the exercisers' reduced body mass index; and 3) HDL2 increased significantly less in dieters than in exercisers. In dieters, low calorie intake might mitigate the effects of weight loss on HDL2. PMID- 2317912 TI - Interstudy variability of coronary flow reserve. Influence of heart rate, arterial pressure, and ventricular preload. AB - To define the long-term variability of serial coronary flow reserve (CFR) measurements in humans and to evaluate the influence of changes in heart rate, mean arterial pressure, and left ventricular preload on CFR, 45 patients with normal left ventricular function (38 cardiac allograft recipients, five patients with normal coronary arteries, and two patients with minimal coronary artery disease [less than 50% diameter stenosis]) were studied. CFR (ratio of peak hyperemic [h] to resting [r] coronary blood flow velocity [CBFV]) was measured with a 3F coronary Doppler catheter and intracoronary papaverine. Initial CFR measurements were highly correlated with repeat measurements obtained 11 +/- 0.6 months later (r = 0.95; mean absolute difference, 0.3 +/- 0.1; n = 17). Differences in CFR between studies were related to changes in heart rate (r = 0.61, p = 0.01) but not to changes in mean arterial pressure (r = 0.25, p = 0.33). To define the effects of rapid changes in heart rate, mean arterial pressure, and preload on CFR, these variables were altered by atrial pacing, handgrip exercise, and volume expansion, respectively. Atrial pacing produced a rate-related increase in rCBFV but did not change hCBFV. Consequently, CFR was significantly reduced as heart rate was increased progressively from 76 +/- 2 in sinus rhythm (4.5 +/- 0.2) to 100 (3.8 +/- 0.2, p less than 0.05, n = 32) to 120 beats/min (3.2 +/- 0.1, p less than 0.05, n = 7). Despite a 19 +/- 2 mm Hg rise in mean arterial pressure during handgrip exercise, CFR was unchanged from baseline (3.7 +/- 0.3 vs. 3.7 +/- 0.4, p = NS, n = 7) because rCBFV rose proportionally with hCBFV. When pulmonary capillary wedge pressure was increased from 9 +/- 1 to 16 +/- 1 mm Hg after volume expansion, CFR was significantly decreased (from 3.8 +/- 0.2 to 2.9 +/- 0.2, p less than 0.05, n = 9) because rCBFV was increased while hCBFV remained unchanged. Hence, serial CFR measurements in humans are highly reproducible in the absence of conditions known to affect resting or hyperemic coronary blood flow. Increases in heart rate or preload reduced CFR because rCBFV was increased while hCBFV was unchanged. In contrast, changes in mean arterial pressure did not alter CFR. Proper interpretation of CFR measurements should take into account the hemodynamic conditions at which they are obtained. PMID- 2317913 TI - Mean transit time for the assessment of myocardial perfusion by videodensitometry. AB - The intrinsic limitations of coronary arteriography to predict the physiological effects of coronary obstructions are well known. Therefore, more direct assessments of the functional significance of coronary stenoses are becoming increasingly important. Study of contrast passage by electrocardiogram-triggered digital radiography has been proposed as a way of assessing changes in myocardial perfusion. The main problems in this approach are the limited time for motionless image acquisition, the potential alteration of vascular volume between different states, and the changing flow pattern induced by contrast agents. This has led to empiric substitution of mean transit time (Tmn) by other time parameters and to representation of vascular volume by maximal contrast intensity (Dmax). To avoid these problems, intact dogs were studied during almost motionless image acquisition of 20-25 consecutive paced heart beats obtained with synchronous radiographic pulses. In this way, unequivocal and reproducible determination of Tmn was possible. Constant and maximal vascular volume was created by continuous infusion of dipyridamole, and it was proved that coronary flow in this model was not influenced by contrast injections. Flow in the circumflex artery was measured by a ring mounted and calibrated Doppler probe. In each dog, flow in the circumflex artery was varied by a balloon occluder in 12 small steps (range, 0 174 +/- 42 ml/min). Inverse appearance time (1/Tapp), Dmax, Dmax/Tapp, inverse time of maximal intensity (1/Tmax), and 1/Tmn were calculated and the relations of these parameters to measured flow were investigated. Tmn proved to be the most reliable parameter for this purpose (r = 0.97 +/- 0.02; mean +/- SD), followed by Tmax (r = 0.93 +/- 0.04). Dmax failed to represent vascular volume but, in fact, showed a moderate correlation with flow (r = 0.78 +/- 0.22), as did Tapp (r = 0.64 +/- 0.18, 0.75 +/- 0.27, and 0.59 +/- 0.26 for the three definitions of Tapp used in this study). Dmax/Tapp correlated better with flow than either component separately. Our results indicate that the mean transit time calculated by videodensitometry can be used to accurately assess changes in myocardial perfusion strictly according to the original principles of indicator dilution theory. PMID- 2317914 TI - Left ventricular unloading during reperfusion does not limit myocardial infarct size. AB - To determine whether venting the left ventricle during coronary reperfusion limits myocardial infarct size, we studied paced (200 beats/min) Langendorff rabbit hearts, perfused with blood from a support rabbit. A left coronary artery was occluded for 60 minutes, followed by 2 hours of reperfusion. Four experimental conditions, as follows, were used: In group 1 (control), the hearts contracted isovolumetrically on a fluid-filled balloon in the left ventricle during both occlusion and reperfusion. In group 2, the balloon was present only during occlusion, and the heart was vented during reperfusion. Hearts in group 3 were vented during occlusion and developed pressure during reperfusion. In group 4, the left ventricle was vented during occlusion and reperfusion. Perfusion pressure (91.2 +/- 0.9 mm Hg) and coronary flow (0.88 +/- 0.03 ml/min/g) were not different between groups. Left ventricular pressures (mean of all groups) were 87.3 +/- 1.5 mm Hg systolic and 6.5 +/- 0.6 mm Hg diastolic. Infarcted myocardium was assessed by triphenyl tetrazolium staining and expressed as a percentage of the area at risk, as measured by fluorescent particles. Venting during both ischemia and reperfusion (n = 10) did result in significantly smaller infarcts than in the unvented controls (n = 10), that is, 13 +/- 5% vs. 41 +/- 6%, respectively. Venting only during reperfusion (n = 10) or occlusion (n = 11) did not significantly limit infarct size (57 +/- 6% and 32 +/- 5%, respectively), as compared with controls. Thus, the clinically feasible intervention of left ventricular venting during reperfusion was not cardioprotective. PMID- 2317915 TI - Comparative effects of pacing-induced and flow-limited ischemia on left ventricular function. AB - We compared left ventricular (LV) myocardial blood flow and function accompanying severe demand ischemia (rapid atrial pacing in the presence of critical bilateral coronary stenoses) and supply ischemia (complete bilateral coronary occlusion) of the same ischemic regions in 14 pentobarbital-anesthetized dogs. Pacing-induced ischemia resulted in pronounced reductions in average regional epicardial blood flow (0.8 +/- 0.4 vs. control 1.2 +/- 0.4 [+/- SD] ml/g/min, p less than 0.05) and endocardial blood flow (0.4 +/- 0.1 vs. control 1.3 +/- 0.3 ml/g/min, p less than 0.05). More severe reductions in average regional epicardial and endocardial blood flow were seen after bilateral coronary occlusion (BCO) (0.3 +/- 0.3 and 0.1 +/- 0.1 vs. control 1.3 +/- 0.3 ml/g/min, p less than 0.05, respectively). Hemodynamics of postpacing ischemia (PPi) were consistently characterized by systolic impairment including depressed systolic contractile performance [(+)dP/dtmax 1,281 +/- 442 vs. control 2,173 +/- 775 mm Hg/sec, p less than 0.05], ventricular dilation (left ventricular [LV] end-diastolic dimension [EDD] 47.6 +/- 7.8 vs. control 44.7 +/- 8.6 mm, p less than 0.05), and an increase in LV end-diastolic pressure (EDP) (14.4 +/- 2.8 vs. control 4.2 +/- 2.8 mm Hg, p less than 0.05). Abnormalities in early and late diastolic function with PPi included increased time constant of isovolumic relaxation (78.0 +/- 40.4 vs. control 46.4 +/- 20.5 msec, p less than 0.05) and increased chamber stiffness (1.9 +/- 0.77 vs. control 0.81 +/- 0.55 mm Hg/mm, p less than 0.05), respectively. The LV diastolic pressure-dimension relation, however, shifted upward and to the right in eight of nine animals, whereas an upward shift was observed in only one animal. Thus, in this model of postpacing ischemia, we observed contractile failure and passive changes in diastolic function. Alterations in ventricular function occurred consistently earlier and to a greater extent during BCO than PPi, including higher LVEDP (25.3 +/- 8.1 vs. 14.9 +/- 6.6 mm Hg, p less than 0.05), greater ventricular dilation (delta LVEDD 4.9 +/- 2.5 vs. 3.5 +/- 2.8 mm, p less than 0.05), and reduced minor-axis dimension shortening (3.3 +/- 3.1% vs. 6.5 +/- 3.6%, p less than 0.05). To detect potential qualitative differences in ventricular function between the two types of ischemia, we evaluated hemodynamics at comparable loading conditions (30 seconds to 1 minute of BCO).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2317916 TI - Effects of caffeine and ryanodine on delayed afterdepolarizations and sustained rhythmic activity in 1-day-old myocardial infarction in the dog. AB - Caffeine and ryanodine are known to modulate oscillatory release of Ca2+ from the sarcoplasmic reticulum. The effects of caffeine and ryanodine on delayed afterdepolarizations (DADs) and sustained rhythmic activity in subendocardial Purkinje fibers surviving 1-day-old myocardial infarction in the dog were studied with standard microelectrode techniques. In preparations that showed sustained rhythmic activity, a high concentration of caffeine (10 mM) and ryanodine (10(-7) and 10(-6) M) slowed and terminated the sustained rhythmic activity and markedly suppressed DADs. An increase in the temperature of the tissue bath from 37 degrees to 39 degrees C did not change these results. In quiescent normal and infarcted preparations, a low concentration of caffeine (0.5 mM) differentially induced DADs in ischemic but not in normal Purkinje fibers, increased the amplitude of existing DADs, and brought subthreshold DADs to threshold potential that caused triggered activity. Our results are consistent with the hypothesis that triggered activity arising from DADs characterizes the sustained rhythmic activity in endocardial preparations 1 day after infarction and indicate an important role for the sarcoplasmic reticulum in the genesis of DADs and triggered activity in this model. PMID- 2317917 TI - Effect of epicardial patch electrodes on transthoracic defibrillation. AB - To improve survival rates in patients undergoing surgical ablative procedures for malignant ventricular tachycardia (VT), a frequent practice is to implant epicardial patch electrodes at the time of map-guided surgery. After operation, patients with inducible VT often receive an automatic internal cardioverter/defibrillator (AICD) implant, whereas patients with noninducible VT usually do not. In the event that spontaneous, hypotensive VT or ventricular fibrillation should subsequently occur in the patient with noninducible VT, however, transthoracic defibrillation and resuscitation may prove difficult, because the patch electrodes are insulated with silicone rubber that can reduce the amount of current traversing the myocardium and thus can increase transthoracic defibrillation threshold (DFT). In this study, DFT was determined in mongrel dogs to test the hypothesis that epicardial patch electrodes elevate threshold. This study was also designed to assess the effect of patch electrode orientation and size on DFT. In the first protocol (perpendicular orientation), small epicardial patch electrodes (surface area, 30 cm2) were sutured to the epicardial surfaces of the anterior right and posterior left ventricles in 15 dogs so that the center axes of the patch electrodes were coincident and perpendicular to the coincident center axes of the transthoracic electrodes. The effect of two large epicardial patch electrodes (surface area, 53 cm2) on transthoracic DFT was also examined in eight of these dogs. In the second protocol (parallel orientation), small patch electrodes were sutured to the lateral surfaces of the right and left ventricles in seven dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2317918 TI - 111In platelet scintigraphy and risk stratification for embolization from chronic left ventricular thrombi. PMID- 2317919 TI - Iatrogenic Lutembacher's syndrome revisited. PMID- 2317920 TI - Dipyridamole thallium 201 imaging. How safe is it? PMID- 2317921 TI - What do muscles have to do with lipoproteins? PMID- 2317922 TI - Upward shift and outward bulge. Divergent myocardial effects of pacing angina and brief coronary occlusion. PMID- 2317923 TI - Treatment of patients with heart failure. PMID- 2317924 TI - Coarctation of the aorta: long-term follow-up and prediction of outcome after surgical correction. PMID- 2317925 TI - Characterization of prolidase I and II from erythrocytes of a control, a patient with prolidase deficiency and her mother. AB - Prolidase I (EC 3.4.13.9) was purified to homogeneity from the erythrocytes of a normal human (control) and the patient's mother, and prolidase II from erythrocytes of a control and the patient's mother, and prolidase from the patient's erythrocytes was also highly purified. The various properties of the patient's prolidase were compared to those of prolidase from a control and the patient's mother. Prolidase I from a control and the patient's mother had a molecular weight of about 112,000, and was composed of two subunits with an identical molecular weight of 56,000. The Km values for Gly-Pro of the control's and the patient's mother's prolidase I were 2.90 +/- 0.22 and 2.88 +/- 0.27 mM, but the Vmax values for Gly-Pro of the mother's enzyme was reduced about 30% compared to that of control enzymes (mother: 6.02 units/mg protein, control: 22.21 units/mg protein). Isoionic points of these enzymes by chromatofocusing were pH 4.6 approximately 4.7. Prolidase II from the control and the patient's mother, and the patient's prolidase had a molecular weight of about 185,000, and was composed of two subunits with an identical molecular weight of 95,000. The Km and Vmax values for various substrates of prolidase II from a control and the patient's mother, and the patient's prolidase were almost the same. PMID- 2317927 TI - Validation of a method to measure the uptake of [3H]dopamine by human platelets. AB - We have assessed the validity of using platelet-rich plasma (PRP) to measure dopamine uptake by platelets. In addition, we report on a pilot study comparing [3H]dopamine uptake by PRP from psychotic patients to that by PRP from healthy volunteers. Uptake of radiolabelled dopamine by PRP was related to the concentration of [3H]dopamine added and correlated with platelet number. [3H]dopamine uptake by PRP was not altered by varying pH (6.8 to 8.0) or by the time PRP was incubated prior to the addition of the radiolabelled dopamine. 11.7 +/- 0.34% (mean +/- SEM) of [3H]dopamine added to plasma was precipitated by polyethylene glycol (PEG) and appeared to be associated with a large molecular mass component of plasma. The amount of PEG precipitable [3H]dopamine did not correlate with dopamine uptake (r = 0.02) or differ between patients and controls. Uptake of [3H]dopamine by PRP from 52 volunteers (26 M, 26 F; age, 18 75 yr), expressed as the area under the dopamine uptake curve up to 60 min in arbitrary units, ranged from 72-285 for males and 59-455 for females. Comparing [3H]dopamine uptake by PRP from 15 psychotic patients to these sex-specific reference ranges 9 of 13 PRP from schizophrenic patients had [3H]dopamine uptake outside the normative values whereas the two non-schizophrenic patients did not differ from normal. Dopamine uptake by PRP may be useful in the study of diseases with altered dopaminergic activity in the CNS. PMID- 2317926 TI - Immunochemical assays of serum proteins: a European external quality assessment survey and the effects of calibration procedures on interlaboratory agreement. AB - An external quality assessment survey of immunochemical assays of 9 proteins (immunoglobulins G, A and M, complement components C3 and C4, alpha1-antitrypsin, orosomucoid, haptoglobin and transferrin) in 5 European countries (Austria, France, Hungary, Italy and UK) showed inter-country differences in the mean values obtained. Reprocessing of the results using one of the two specimens distributed as a 'calibrant' effectively eliminated or reduced substantially these differences. Consideration of the methods used by participants confirmed previous indications from national surveys that the differences were due to lack of agreement among commercial calibrants. Such interlaboratory variations were also minimised by the 'calibration' in this survey. The role of European working calibration materials in ensuring interlaboratory agreement on an international basis is discussed. PMID- 2317928 TI - Accumulation of mannosyl-beta(1----4)-N-acetylglucosamine in fibroblasts and leukocytes of patients with a deficiency of beta-mannosidase. AB - Cultured fibroblasts from two brothers with beta-mannosidosis were shown to accumulate the disaccharide mannosyl-beta(1----4)-N-acetylglucosamine in amounts of 52 and 68 nmol/mg protein. Structural identification of the Man beta(1--- 4)GlcNAc, isolated by HPLC, was performed by 500-MHz 1H-NMR spectroscopy and sugar composition analysis. Control fibroblasts did not contain a detectable amount of Man beta(1----4)GlcNAc. The disaccharide was also present in leukocytes from these patients, but not in controls, as could be demonstrated by thin-layer chromatography and sugar composition analysis. However, the amounts in leukocytes (5 and 6 nmol/mg protein) were much smaller than those in fibroblasts. PMID- 2317929 TI - Characterization of aminopeptidases in human kidney soluble fraction. AB - Fractionation of human kidney soluble extract (with which the majority of cellular aminopeptidase activity is associated) via anion exchange chromatography resolved four types of separable aminopeptidase (relative activity in parenthesis): alanyl aminopeptidase (EC 3.4.11.14; 50%); arginyl aminopeptidase (EC 3.4.11.6; 30%); leucyl aminopeptidase (EC 3.4.11.1; 18%) and pyroglutamyl aminopeptidase (EC 3.4.19.3; 2%). The further purification (via gel filtration chromatography and preparative electrophoresis) and characterization of each aminopeptidase has been described; the aminopeptidase tissue profile for human kidney was found to be similar to that previously obtained for human skeletal muscle and brain tissue using a similar experimental approach, i.e. the same enzymes, with corresponding similar characteristics, are present in each tissue. These results suggest that soluble aminopeptidases may be of fundamental importance in general cell protein catabolism. Degradation of the following aminoacyl-AMC derivatives via kidney soluble extract has been shown to be due principally to hydrolysis by alanyl aminopeptidase: glutamyl, glycyl, isoleucyl, methionyl, ornithyl, phenylalanyl, prolyl, seryl, tyrosyl and valyl. We would suggest that measurement of the soluble extract-derived aminopeptidases described in this paper in urine may lead to an improvement upon existing assay procedures for early detection of kidney damage. PMID- 2317930 TI - Post-transcriptional modification of serum creatine kinase in infected intensive care patients. AB - Low creatine kinase (CK) activities in serum are associated with high fatality rates in intensive care patients. The underlying mechanisms for this phenomenon were investigated. No correlation was found with other biochemical markers of inflammation (CRP, alpha-1 acid glycoprotein, alpha-2 macroglobulin). In the patients' serum a factor is described which is capable of increasing the activation energy of normal CK-MM, indicating molecular changes in CK-structure. This factor is likely to be an enzyme which is present in liver tissue and in fibroblasts. Similar results were obtained after in vitro treatment of normal serum samples with arylsulfatase. Furthermore, bacterial strains isolated in the serum of intensive care patients were found to alter human CK structure. In the investigated patient group, changes in CK activation energy are influenced by serum factors other than carboxypeptidase N activity. PMID- 2317931 TI - Comparison of serum and urine neopterin concentrations in patients with HIV-1 infection. AB - Urine and serum neopterin concentrations are now widely used to monitor patients with HIV-1 infection. However, there are no published studies comparing the levels in urine and serum, and relating both to the patients' immune status. Urine and serum neopterin concentrations correlated closely in our study population of 37 HIV-1 seropositive patients (34 homosexuals, 3 drug addicts) and 10 HIV-1 seronegative homosexuals. Our data further show that urine and serum neopterin concentrations correlate almost identically with the clinical and immunological presentation of HIV-1 infected individuals, as expressed by the Walter Reed Staging classification. In addition, there was no difference between the correlation of neopterin concentrations in either serum or urine with the Quetelet indices. It will depend on the clinical situation whether blood or urine sampling is preferred. Collection and handling of urine samples from HIV infected patients is less risky to health care personnel in HIV settings. PMID- 2317932 TI - Enzymatic erythrocyte creatine determinations as an index for cell age. AB - Creatine concentration in red blood cells was determined after ammoniumsulfate precipitation on a clear hemoglobin-free filtrate with a new enzymatic assay making use of bacterial creatinase. The method described is more specific than Griffiths' method and can easily be mechanised and adapted for use in a routine laboratory using classical automated equipment. By contrast with Griffiths' method no significant interferences of amino acids and creatine-like molecules were found. Reference values for this method were 0.379 +/- 0.076 mmol/l. In patients with high turnover of erythrocytes, e.g. haemodialysis patients (0.529 +/- 0.122 mmol/l), and renal insufficiency patients (0.565 +/- 0.145 mmol/l), significantly increased creatine concentration in erythrocytes were observed. Low erythrocyte creatine concentrations were found in chronic ambulatory dialysis patients (0.311 +/- 0.042 mmol/l). PMID- 2317933 TI - A microalbuminuria assay using bromphenol blue. AB - A simple microalbuminuria assay using bromphenol blue/glycine reagent is described. Urine samples were prepared using gel filtration on Sephadex G-50 minicolumns and absorbance was measured at 610 nm 20 s after mixing 10 parts of eluate and 1 part of reagent. The detection limit of this method was 3 mg/l; within-run and between-run precision was between 0.5 and 4.1% for borderline and raised albumin concentrations. The recovery of albumin added to samples was 98.7 +/- 2.5%. Results obtained by this method correlated closely with values obtained by radial immunodiffusion (r = 0.987). The test is cheap (reagent costs about 5 cents) and suitable for the non-specialist laboratory. PMID- 2317934 TI - A sensitive and specific assay for granulocyte elastase in inflammatory tissue fluid using L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide. AB - Granulocyte elastase (GE, EC 3.4.21.37) is a key enzyme in tissue injury. To elucidate the role of GE in tissue injury, a new method of measuring GE activity in various inflammatory tissue fluids was developed using diazotization and the chromogenic synthetic substrate, L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide (S-2482). GE activity demonstrated first order kinetics in the range from 1.9 to 30 U/l. Other proteases, such as pancreatic elastase, trypsin, and chymotrypsin did not hydrolyze S-2484. This assay permits the determination of GE activity with a coefficient of variance less than 7.8% and 95.6 to 105.4% recovery. With this method, hydrolytic GE activity was found to be increased in bronchoalveolar lavage fluid from patients with ARDS or pneumonia, synovial fluid from patients with rheumatoid arthritis, and blister fluid from burn patients. PMID- 2317936 TI - Spectrophotometric evaluation of results of the ascorbate and the ascorbate cyanide screening tests for glucose-6-phosphate dehydrogenase deficiency. PMID- 2317935 TI - Alterations in manganese and iodide contents in human thyroid tumors; a correlation between the contents of essential trace elements and the states of malignancy. PMID- 2317937 TI - Detection of neuron specific enolase concentrations in cerebrospinal fluid from patients with neurological disorders by means of a sensitive enzyme immunoassay. AB - An enzyme linked immunosorbent assay (ELISA) for the detection of neuron specific enolase (NSE) in cerebrospinal fluid (CSF) was developed. The sensitivity of the ELISA was less than 1 microgram/ml. This sensitivity is comparable with radioimmunoassays which have the disadvantage that radiolabelled products are used. The developed assay was used to measure cerebrospinal fluid neuron specific enolase (CSF-NSE) levels in 1178 patients with neurological disorders to establish its potential usefulness and clinical application. CSF-NSE levels in this group of patients were independent of sex and no correlation with age was found. CSF-NSE was significantly increased in Creutzfeldt-Jacob disease, meningeal hemorrhage, thrombosis, Guillain-Barre syndrome and in schizophrenia. PMID- 2317938 TI - Automated enzymatic assays for the determination of intestinal permeability probes in urine. 1. Lactulose and lactose. AB - Lactulose is becoming the disaccharide of choice in the dual sugar assessment of passive permeability of the small intestinal mucosa. However its more widespread use is hampered by current analytical methods which are tedious and time consuming. An automated spectrophotometric technique for the assay of this sugar in urine is presented in which lactulose is linked by a series of enzyme reactions to the equimolar production of NADPH. In addition to lactulose, the procedure also gives accurate values for lactose, glucose and fructose in the urine sample. The assay has been shown to be highly specific for lactulose and lactose and was not affected by high concentrations of other sugars or other urinary constituents. Within assay and between assay precision were similar with the coefficient of variation for both sugars in the range 0.4-1.6%. The technique represents a significant improvement in time, simplicity and precision on existing methods of analysis. PMID- 2317939 TI - A new sensitive microassay for the measurement of erythrocyte glycogen. AB - Conventional ethanol precipitation of sub-microgram amounts of glycogen leads to low yields (less than 50%). Quantitative recoveries of 90% were attained, however, when the isolation temperature was raised to 50 degrees C and ethanol was replaced by the less polar propan-2-ol. This improvement enabled development of an erythrocyte assay for glycogen which was both sensitive (0.1 microgram glycogen) and required only 1 ml of whole blood. 26 paediatric specimens were analysed and a reference range of values from undetected to 78 micrograms glycogen/g haemoglobin (Hb) was obtained. PMID- 2317940 TI - Development and validation of an automated enzyme assay for paracetamol (acetaminophen). AB - A rapid, enzymatic assay for serum or plasma paracetamol has been developed with the potential for adaptation to a wide range of clinical analysers. The method involves the action of an amidase enzyme to produce 4-aminophenol from paracetamol, which in turn reacts with 8-hydroxyquinoline in the presence of manganese ions to form a blue dye. Two stable reagents are used and excellent precision is achieved over the drug concentration range 0-2.5 mmol/l. The method, which is complete within 6 min, has been validated using a Monarch centrifugal analyser and shows no significant interference from endogenous serum compounds, drugs or paracetamol metabolites. PMID- 2317941 TI - Molecular size heterogeneity of immunoglobulins in health and disease. AB - The molecular size of serum IgG, IgA and IgM in patients with a variety of monoclonal and polyclonal immune disorders has been determined by a sensitive immunoblotting technique. IgM, IgA and IgG3 paraproteins from patients with B cell lymphoproliferative disorders frequently polymerize with IgA paraproteins demonstrating two polymeric series, the basic unit of the more dominant series being monomeric IgA, and the second consists of a basic unit having a molecular mass of approximately 70 kD heavier than monomeric IgA. The molecular nature of this heavier IgA moiety was shown to be IgA covalently bound with a single molecule of serum albumin or alpha 1 antitrypsin and this moiety was also observed in small quantities in sera from healthy subjects. IgM paraproteins, particularly from patients with malignant lymphoproliferative disorders, consisted of varying proportions of decamers, pentamers and monomers together with other low molecular weight IgM oligomers. Paraproteins from patients with benign conditions showed less tendency to exist in multiple molecular weight forms. Serum immunoglobulins from patients with polyclonal immune disorder also showed molecular sized heterogeneity. Significantly increased levels of dimeric IgA were observed in patients with alcoholic cirrhosis and Felty's syndrome, while low molecular weight IgM was commonly seen in patients with autoimmune disorders. In these latter disorders monomeric IgM correlated significantly with the serum IgM level suggesting a disorder of assembly of the IgM subunits during an ongoing IgM immune response. We have demonstrated considerable molecular size heterogeneity of serum immunoglobulins both in health and disease and have indicated some possible clinical associations. PMID- 2317942 TI - Suppression of HLA class II expression on thyrocytes by interferon-alpha 1. AB - Inappropriate expression of HLA class II molecules by human thyroid epithelial cells (thyrocytes) is commonly associated with autoimmune thyroid disease. HLA class II expression can be modulated in thyrocytes in vitro by a variety of substances: in particular, it is readily induced by interferon-gamma (IFN-gamma). Here we show that recombinant IFN-alpha 1 (rIFN-alpha 1) does not induce HLA class II expression by thyrocytes, but rather it suppresses the induction of such expression by rIFN-gamma. Similar effects were observed with IFN-alpha derived from a lymphoblastoid cell line. The effect of rIFN-alpha 1 on thyrocytes differs from its effect on human monocytes, reported by others, in which it was found to enhance the expression of HLA class II. Thus, rIFN-alpha 1 appears to have a differential effect on HLA class II expression, depending on the cell type involved. PMID- 2317943 TI - IgA polyspecific autoantibodies in IgA nephropathy. AB - The specificity of circulating and kidney-bound IgA during IgA nephropathy is still a matter of discussion. In the present study, high levels of IgA antibodies directed against a panel of self and non-self antigens were found in the serum from patients with IgA nephropathy and were eluted from four out of the seven kidney biopsies studied. After immunoadsorption of pooled selected serum samples on TNP and actin-coated columns, polyspecific IgA antibodies were eluted. This supports the hypothesis that IgA-bearing B cells clones most probably producing polyspecific antibodies are a major feature of human IgA nephropathy. These findings also suggest that it may be hazardous to draw conclusions from the finding of apparently monospecific IgA antibodies in this condition. PMID- 2317944 TI - Depressed lymphocyte transformation and the role of prostaglandins in atopic dermatitis. AB - We have shown that peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis have a reduced in vitro proliferative responsiveness to concanavalin A when compared with non-atopic controls. Addition of the cyclo oxygenase inhibitor indomethacin caused a significant enhancement of the mitogen response in the patients, indicating a suppressive effect of cyclooxygenase products. We have further demonstrated increased levels of prostaglandin E2 in the supernatants of the PBMC cultures and increased levels of IgE immune complexes in the sera of the atopic dermatitis patients and therefore hypothesize that IgE immune complexes may cause increased monocyte production of prostaglandins which in turn appears to be responsible for a reduced lymphocyte proliferation. PMID- 2317945 TI - HLA-DQ-controlled T cell response to soluble egg antigen of Schistosoma japonicum in humans. AB - We analysed regulatory mechanisms of the human T cell response to soluble egg antigen (SEA) of Schistosoma japonicum in vitro. SEA is a crude antigen mixture containing numerous epitopes. We obtained SEA-induced T cell lines from five patients with chronic schistosomiasis japonica, and tested their proliferative response to molecular weight fractions of SEA. Although all T cell lines showed strong responses to crude SEA, there was a heterogeneity in fraction-driven responsiveness. All but one T cell line tested failed to respond to SEA fraction I (mol. wt greater than 18 kD). One patient who was typed as HLA-DQw1/w4, did not show proliferation of CD4+ T cells to fraction I; however, a fraction I-driven helper T cell response was observed when we added HU-11 monoclonal antibody specific for HLA-DQw1/w4. This indicated that the patient had helper T cells to the fraction even though their response was suppressed. Because HLA-DQ had an effect on functional expression of suppressor T cells, it was suggested that there was epitope-specific regulation of the T cell response to SEA, and HLA-DQ controlled immune suppression might be involved in the regulatory system in human chronic schistosome infection. PMID- 2317946 TI - Combination chemo-immunotherapy: kinetics of in vivo and in vitro generation of natural killer cells and lymphokine-activated killer cells in the rat. AB - Rats received a single high dose of cyclophosphamide (Cy) (150 mg/kg), followed 48 h later (on day 0) by immunization with a T cell-dependent soluble antigen, ovalbumin in Freund's complete adjuvant (FCA). The effect of this treatment on lymphoid cell subpopulations in the spleen, natural killer (NK) cell and interleukin-2 (IL-2) induced lymphokine-activated killer (LAK) cell activity was examined. Cy (with and without ovalbumin) caused a large relative increase (by day 14) in splenic OX8+, OX19- cells with NK morphology. A marked relative increase in fresh NK cell activity was noted after Cy + ovalbumin, but not consistently after Cy alone. Elevated NK activity was Cy dose- and time dependent, was evident within 7 days post Cy/ovalbumin and persisted for at least 28 days. Pooled splenic mononuclear cells (MNC), obtained 14 days after Cy/ovalbumin, lost all cytolytic activity against YAC-1 cells when cultured in the absence of human recombinant IL-2 (rIL-2). In contrast, similarly maintained cells from normal rats displayed NK activity higher than normal 'fresh' levels. Upon culture in medium containing 500 U/ml rIL-2, however, 'augmented' NK activity was equivalent, on a per-cell basis, in both normal and Cy/ovalbumin pretreated groups. LAK activity generated in vitro (i.e. against NK-resistant target cells) was significantly lower in the latter group, and the overall yield of cells was reduced. By day 21 after Cy/ovalbumin, augmented NK activity was significantly greater than controls, on a per-cell and total culture yield basis. Moreover, LAK activity was now similar between groups. It is concluded that the chemotherapy/immunization protocol which we have used can greatly enhance NK activity in vivo and that these cells are responsive to induction of LAK activity by IL-2 in vitro. PMID- 2317947 TI - Reduced natural cytotoxic cell activity in patients receiving cisplatin-based chemotherapy and in mice treated with cisplatin. AB - In mice natural cytotoxic (NC) cells are known to play a role in the rejection of tumours that are sensitive to NC-mediated lysis. We have recently shown that in vitro human and murine tumour cells become more sensitive to lysis mediated by NC cells in the presence of the anti-cancer drug cisplatin. If NC activity plays a role in tumour surveillance in humans, then the ability of NC cells to eliminate tumours in patients treated with cisplatin would not only be dependent on cisplatin increasing the sensitivity of tumours to NC mediated lysis, but would also depend on the maintenance of high levels of NC activity during chemotherapy. Here we report that patients receiving chemotherapy that included cisplatin showed a time-dependent reduction in NC activity. NC activity was normal 1 day after treatment; however, 15 days after treatment patients had an eight- to 16 fold reduction in NC activity that returned to normal levels by day 21. The reduction in NC activity of patients was coincident with a reduction in circulating monocytes. Mice treated with only cisplatin showed a similar reduction in NC activity. Mice treated with cisplatin had a reduced level of NC activity that was first apparent 8 days after treatment, reached a nadir on day 15, and returned to normal levels on day 22. PMID- 2317949 TI - HL-60 cells induced to differentiate towards neutrophils subsequently die via apoptosis. AB - The human promyelocytic HL-60 cell line can be induced to differentiate to neutrophil-like cells in response to a variety of chemical stimuli. We have found that retinoic acid-treatment of HL-60 cells over a period of 6-8 days resulted in a progressive increase in the proportion of cells with mature neutrophil morphologies and was closely followed by an increase in the proportion of cells exhibiting the morphological characteristics of apoptosis, the non-pathological mode of cell death. Using Percoll step-density gradients we have demonstrated a marked increase in the buoyant density of these cells and have used this density difference to obtain enriched fractions of cells for more detailed study. Degradation of the nuclear DNA of these cells into integer multiples of about 200 base pairs, indicative of endogenous endonuclease activation a major characteristic of programmed cell death, was also demonstrated. From these observations we conclude that the mode of cell death in cultures of terminally differentiated HL-60 cells is that of apoptosis. These results parallel those of a recent report which has shown apoptosis to be the mode of cell death of ageing peripheral blood neutrophils. Because of this, we believe that our observations further validate the use of the HL-60 cell line as a model system for the study of human granulopoiesis in vitro and further, that this model system may be useful for gaining insight into the underlying mechanisms involved in apoptosis. PMID- 2317948 TI - The effect of the immunomodulator agent AS101 on interleukin-2 production in systemic lupus erythematosus (SLE) induced in mice by a pathogenic anti-DNA antibody. AB - The role of the synthetic immunomodulator AS101 on the production of interleukin 2 (IL-2) by spleen cells of mice with SLE was investigated. BALB/c female mice, in which SLE was induced by immunization with the pathogenic idiotype of anti-DNA antibody 16/6 Id were treated with AS101 for 7 weeks 2 and 4 months after induction of the disease. The ability of the splenocytes of the mice with SLE to produce IL-2 was restored after administration of AS101. This effect was particularly impressive when the 7-week AS101 treatment was initiated 4 months after immunization. Despite its beneficial effect on IL-2 production, AS101 exerted no influence on the titres of autoantibodies in the sera of the mice. It also had no effect on clinical parameters of SLE, such as the increased sedimentation rate, proteinuria and low white blood cell counts. Our data indicate that defective IL-2 production in SLE is probably secondary to other disease processes and is not necessarily associated with the production of autoantibodies in this disorder. PMID- 2317951 TI - Database utilization: identifying students at risk of poor academic performance. PMID- 2317950 TI - Human milk contains proteins that stimulate and suppress T lymphocyte proliferation. AB - The modulatory effect of human milk proteins from colostrum and late milk on the proliferative response of human T lymphocytes activated by mitogens (OKT3 and leucoagglutinin from Phaseolus vulgaris) and alloantigens was studied. High concentrations (10-100 micrograms/ml) of crude colostral milk proteins had an inhibitory effect on T cell growth while low concentrations (0.1-1 microgram/ml) enhanced T cells growth. In contrast, proteins from late milk did not inhibit T lymphocyte proliferation while the enhancing effect was retained. Colostrum was fractionated by ammonium sulphate precipitation and gel filtration on sepharose 6B. The inhibitory activity was recovered in a protein fraction containing lactoferrin as its major component. Lactoferrin was, however, not responsible for the observed inhibition. On the contrary, lactoferrin in most cases augmented the proliferative response induced by polyclonal activators. The inhibitory activity was found to bind concanavalin A-sepharose suggesting an association with glycoprotein. Inhibitory fractions contained glycoproteins of the following molecular sizes 26, 74/76 (doublet), 84, 145 and 160 kD under reducing conditions. The inhibitory effect appeared to be lymphocyte specific since the active fraction did not inhibit the growth of tissue culture cells (HeLa cells and human fibroblasts) or bacteria. Furthermore, the fraction was not toxic for lymphocytes. The inhibitory colostrum factor may prevent the newborn from overreacting immunologically against the environmental antigens encountered at birth. PMID- 2317952 TI - Suppression of rat tumor colonies in the lung by oxygen at high pressure is a local effect. AB - The effect of hyperbaric oxygen (HBO) on the growth of anaplastic carcinoma colonies in rat lungs after intravenous tumor cell injection was studied. From the first day after tumor cell injection, the rats were exposed to HBO for 16-21 days, 90 min per day. Oxygen at a pressure of 300 kPa (3.0 ATA) significantly decreased the number of lung tumor colonies and increased the survival of tumor bearing rats, whereas the application of oxygen at a pressure of 100 kPa had no effect. An oxygen-nitrogen normoxic mixture balanced with nitrogen to 300 kPa (3.0 ATA) did not affect the number of colonies, suggesting that the effect was specific for oxygen and not for the increased pressure itself. A 6-day application of oxygen at a 300 kPa pressure suppressed the growth of lung tumor colonies when applied on days 1-6 and 7-12 after intravenous tumor cell injection, but had no effect when applied on days 13-18. In contrast to dramatic effects of HBO on the development of artificial lung metastases, the oxygen at the same 300 kPa pressure had no effect on the growth of tumor cells injected in the hind foot. Thus it appears that the suppression of lung tumor colonies by HBO was due to local oxygen effects in the lungs. PMID- 2317953 TI - Morphogenesis as a parallel of invasion: the epithelial-mesenchymal boundary and basal lamina in foetal rat colon. AB - In order to determine whether neoplastic invasion, as it occurs in colonic carcinoma, represents a recapitulation of embryonic events, the development of the crypts and basal lamina of the rat colon was examined in foetuses between 16 and 21 days gestation by light and transmission electron microscopy, autoradiography and morphometric techniques. The thickness of the basal lamina increased from days 16 to 18 of gestation. On days 19 and 20 the basal lamina was found to be significantly thicker in the intercryptal areas than at the base of the crypt. This difference disappeared at 21 days gestation. It was also demonstrated that cell migration and renewal occur in the same manner in the foetal colon as in the adult colon. These features do not resemble closely those seen in neoplastic invasion. PMID- 2317954 TI - The identification of a neutral glycosphingolipid antigenic marker for metastatic cells in the R3230AC rat mammary adenocarcinoma. AB - The process of metastasis is a complex process involving numerous steps, and it is thought that cells able to complete all of these steps and form metastatic foci form a unique subpopulation of cells within the tumor. To study this metastatic subpopulation, a marker for the metastatic cells is required. We have previously described the enrichment of soybean agglutinin binding cells in tumor populations enriched for lymphatic metastasis [1]. In this study we provide evidence that the cell-surface structure binding soybean agglutinin is a neutral glycosphingolipid. Using monoclonal antibodies generated against this glycolipid, highly metastatic tumor populations were depleted of cells containing this glycolipid. These depleted cell populations were found to be equally tumorigenic to that of the untreated population but were much less metastatic. These results suggest that this glycolipid may be a useful marker for metastatic cells. PMID- 2317955 TI - N-methylformamide affects spontaneous metastases of 3LL lines and increases natural killer activity of tumor-bearing mice. AB - The antitumor activity of the polar solvent N-methylformamide (NMF) was evaluated on three lines derived from the Lewis lung carcinoma (3LL), endowed with different metastatic potential. Two administration schedules were tested, these being repeated regimens of NMF (200 mg/kg per dose) for 12 consecutive days, starting 24 h or 6-10 days after tumor implantation (early or late treatment, respectively). The results of the present work can be summarized as follows: (1) NMF regimens did not greatly affect tumor growth behavior of 3LL lines; conversely, they markedly influenced their spontaneous colonizing ability in the lungs, either by delaying early metastatic spread or by reducing the number and size of pulmonary metastases already implanted. (2) A significant increase of NK cell activity during and after early treatment with NMF was observed in the more metastasizing lines, thus suggesting the possibility of an immunomodulating effect of NMF. PMID- 2317956 TI - Reduction of metastasis in a murine mammary tumour model by heparin and polyinosinic-polycytidylic acid. AB - A murine mammary tumour model has been used to test the efficacy of a combination of heparin and the interferon inducer, poly I:C on spontaneous metastasis from a s.c. primary tumour and on experimental metastasis following i.v. injection of tumour cells. This treatment has no effect on the growth of primary tumours, but lung metastases arising from these tumours were reduced. When tumour cells were injected i.v. the number of lung colonies was significantly reduced and survival time extended. Short-term treatment did not prevent the subsequent growth of extravasated, but dormant tumour cells, although mice treated for 8 or 12 weeks survived at least 6 months without any sign of lung colonies. Several mechanisms may contribute to the overall effect of this treatment; a reduction in the mitotic indices of lung colonies (observed in poly I:C treated mice) and also NK cells appeared to be important for the effectiveness of poly I:C since the reduction in experimental metastasis was abrogated by concomitant treatment with anti-asialo GM1 serum. PMID- 2317957 TI - Dual-energy CT-scan quantification of recalcification in osteolyses of the vertebral body due to mammary carcinomas in the course of antineoplastic treatment. AB - Recalcification of osteolyses can be determined by the use of dual-energy CT scanning. Quantitative CT-scans have been performed in a group of 11 female patients with osteolytic metastatic spread of mammary carcinomas under systemic antineoplastic treatment. During their treatment with either chemotherapy or hormones these patients have been investigated every two weeks in a total observation period of three months. Additional to every CT-scan (n = 77) a conventional radiograph was taken. In the course of treatment it was possible to give reliable statements with regard to the response to therapy up to 8 weeks earlier by the use of quantitative CT-scans compared to conventional radiographs. PMID- 2317958 TI - Exogenously administered gangliosides fail to increase in vivo metastatic frequency or in vitro growth of murine neoplastic cells. AB - The influence of gangliosides on tumor growth and frequency of metastasis in vivo, as well as growth of neoplastic cells in vitro, was tested utilizing the mouse fibrosarcoma cell line MN4. In mice receiving intramuscular tumor transplants, injections of a ganglioside mixture twice daily did not influence the tumor volume or the number of spontaneous metastases per animal. Furthermore, in mice receiving the cells by tail vein injection, injections of a ganglioside mixture once or twice daily did not affect the number of metastatic foci in the lungs. Preincubation of neoplastic cells with the ganglioside mixture decreased the number of metastatic foci in the lungs of mice receiving the cells by tail i.v. injection. The addition of ganglioside mixture to the culture medium for up to a 48-h incubation period had no effect, independently of the cell density utilized, on either the rate of DNA synthesis or the relative numbers of neoplastic cells as compared to controls; at higher ganglioside concentrations, growth was actually reduced. These results are interpreted to indicate that gangliosides, under the present conditions, do not influence tumor growth and metastatic neoplastic capacity in vivo, and growth in vitro. PMID- 2317959 TI - Metastatic abilities of murine sarcomas and carcinomas. II. Relationship to cell volume and DNA index. AB - The cell volume and DNA content were determined in 12 murine tumors and correlated with the ability of these tumors to metastasize spontaneously or to form lung nodules when injected i.v. The cell volume significantly correlated with spontaneous metastatic potential of investigated tumors (r = 0.683; 0.02 less than P less than 0.05) but not with the ability of tumor cells to form artificial metastasis. The DNA index significantly correlated with both spontaneous metastasis (r = 0.594; 0.02 less than P less than 0.05), and lung colonization (r = 0.631; 0.02 less than P less than 0.05). The DNA index barely correlated with the cell volume (r = 0.564; P = 0.10). PMID- 2317961 TI - Symposium. Cerebral palsy. PMID- 2317962 TI - Surgery of spinal deformity in cerebral palsy. Twelve years in the evolution of scoliosis management. AB - In order to assess the lessons learned from 12 years of surgery on patients with cerebral palsy and spinal deformity, the cases may be divided into three groups classified according to type of posterior spinal fusion, instrumentation, and time period. Group I (1976-1980) included patients who had Harrington rods, usually with Dwyer instrumentation. Group II (1980-1985) consisted of patients with unlinked Luque or wired-in Harrington rods. Group III (1985-1988) comprised patients with a unit Luque rod extending to the pelvis. Most patients were retarded nonwalkers who had total body involvement, pelvic obliquity, and severe thoracolumbar curves (Group I average, 97 degrees; Group II average, 72 degrees; Group III average, 89 degrees). The frontal plane correction at follow-up study averaged 51% in Group I, 47% in Group II, and 76% in Group III. The correction of the pelvic obliquity averaged 71% in Group I, 58% in Group II, and 86% in Group III. The general trend was toward longer fusion, use of the unit 0.625-cm Luque rod, and first-stage anterior discectomy and fusion without anterior instrumentation. The second-stage posterior arthrodesis and fusion is now performed only one week after the first-stage anterior procedure. Skeletal traction has been abandoned. The Luque rod instrumentation without fusion has also been abandoned. PMID- 2317960 TI - Inhibition of lung colonization of mouse colon 26 adenocarcinoma by recombinant mouse interferon beta through a modification of platelet function. AB - Recombinant murine interferon beta (MuIFN-beta) given i.v. efficiently inhibited both pulmonary arrest and formation of lung colonies of NL-17, a highly metastatic variant of mouse colon adenocarcinoma 26. NL-17 was rather resistant to MuIFN-beta in vitro and was highly resistant to natural killer cells of mice even though they were treated in vivo with MuIFN-beta. Platelets isolated from MuIFN-beta-treated mice showed reduced aggregating activity induced by NL-17. Since lung colonization by NL-17 is influenced by platelet aggregation, the inhibition of colonization by MuIFN-beta could be partly mediated through modification of platelet function in vivo. The effect of MuIFN-beta on platelet function and its subsequent inhibition of lung colony formation give new insights into the action of recombinant MuIFN-beta. PMID- 2317963 TI - Intramuscular lipoma of the deltoid causing shoulder pain. Report of two cases. AB - Intramuscular lipomas have been reported in various regions of the body, and they are usually asymptomatic. Symptomatic lipoma in the deltoid muscle seems not to have been reported previously. Painful lipoma within the deltoid muscle is documented in two middle-aged men. Surgical excision was curative in both cases. PMID- 2317964 TI - Retroversion of the humeral head in the normal shoulder and its relationship to the normal range of motion. AB - Retroversion of the humeral head and the range of motion of the shoulder joint in both the frontal and the scapular plane have been studied in 100 shoulder joints in 50 healthy subjects, 25 men and 25 women. The average angle for humeral head retroversion was 33 degrees on the dominant side and 29 degrees for the nondominant side. There was no difference between genders. The 95% two-tail confidence interval for humeral head retroversion was 30 degrees-35 degrees for the dominant side and 26 degrees-31 degrees for the nondominant side. A larger retroversion angle was consistent with an increased range of external rotation. Mean external rotation in 90 degrees abduction was 105 degrees in the frontal plane and 120 degrees in the scapular plane. External rotation in 90 degrees abduction was greater in women than in men, but there was no difference between dominant and nondominant shoulder joints. The range of motion of rotation was found to be greater than the accepted normal values. PMID- 2317965 TI - Results of reconstruction for failed total elbow arthroplasty. AB - Failure of total elbow arthroplasty leads to difficult and complicated surgical reconstruction. This study evaluates the results of reconstruction after implant removal with respect to pain, motion, and functional ability. Between 1978 and 1985, 11 patients required implant removal. Indications for removal were infection for seven, implant fracture for three, and recurrent dislocation for one. The original diagnosis was rheumatoid arthritis in six elbows and traumatic arthritis in five. The average length of the follow-up period was 5.5 years after implant removal (minimum, two years). Treatment consisted of implant removal and soft-tissue arthroplasty combined with external fixation in ten patients, and attempted arthrodesis with external fixation in one. There were four good, one fair, two poor, and four failed results. Satisfactory results were obtained in seven of the eight elbows in which an anatomic arthroplasty was achieved. This consisted of containment of the ulna by the humeral epicondylar remnants. All eight elbows were pain-free with an average arc of motion of 85 degrees (range, 55 degrees to 120 degrees). They had excellent elbow flexion power; however, triceps strength was often compromised. In the three elbows in which anatomic arthroplasty could not be achieved, one was flail, one was later converted to an arthrodesis with a customized plate, and the third required an immediate arthrodesis. All three were rated as failures. Fractures occurred in five of the 11 elbows. One occurred preoperatively, three occurred intraoperatively, and one occurred postoperatively. All healed satisfactorily during the course of immobilization. The importance of an anatomic arthroplasty when removing a total arthroplasty cannot be overemphasized. Retaining the epicondylar segments is important because satisfactory results were obtained in patients in whom entrapment of the olecranon within the epicondylar ridges was obtained. Such patients can achieve a satisfactory soft-tissue arthroplasty without the use of an interpositional material. When the epicondylar ridges were not retained and there was marked instability, the patients did not achieve satisfactory results. PMID- 2317966 TI - Proximal radioulnar synostosis after repair of distal biceps brachii rupture by the two-incision technique. Report of four cases. AB - In four cases, proximal radioulnar synostosis developed as a complication of distal biceps tendon reattachment through a two-incision technique. The synostosis was excised in all four cases but recurred in two. In each case, the initial reattachment exposed the bicipital tuberosity of the radius anteriorly and exposed the ulna extraperiosteally through a second incision along its subcutaneous border. This two-incision approach may place the patient at risk for synostosis. If two incisions are to be used for distal biceps tendon reattachment, then a limited muscle-splitting approach through the extensor muscle mass, which avoids exposure of the ulna, may be preferable. PMID- 2317967 TI - Signal variability in magnetic resonance imaging of femoral head osteonecrosis. AB - The present study was designed to document the pattern and extent of magnetic resonance imaging (MRI) changes in femoral head osteonecrosis and also to correlate MRI findings with technetium bone scans and computed tomograms. Over a three-year period, MRI was performed on 26 patients who had clinical and roentgenographic evidence of femoral head necrosis in one or both hips. MRI abnormalities were present in all 41 hips with osteonecrosis, even when symptoms were absent and roentgenographic findings were nonspecific or not yet apparent. A single possible false-positive MRI was noted in a hip with mild degenerative change. There was considerable variation in the pattern and extent of MRI abnormalities. The most common findings were irregularity of the subchondral cortical outline (82.9%), an inhomogeneous pattern of signal loss (50%), focal increases in signal intensity with T2 weighting (35.5%), and effusion (33.3%). Regions of dense cancellous bone on computed tomograms correlated with bands of low-intensity MRI signal. In the diagnosis of asymptomatic hips, MRI was clearly more sensitive than technetium bone imaging. The role of MRI in defining prognosis and treatment selection remains to be established. PMID- 2317968 TI - Histologic correlation in magnetic resonance imaging of femoral head osteonecrosis. AB - The present study was undertaken to determine whether a correlation exists between localized magnetic resonance image (MRI) signal behavior and specific histopathologic features of femoral head osteonecrosis. Contiguous, 5-mm coronal MRI sections were compared with corresponding histologic sections from six surgically excised femoral heads. After identifying specific areas of interest on the images, signal intensity was evaluated, both subjectively and objectively, and T1 and T2 relaxation times were calculated. Mean values for these data were compared among the following histologic categories: normal bone, unrepaired dead bone and marrow, unrepaired dead bone with marrow replaced by amorphous debris, and zones of repair. For each type of tissue, MRI signal intensity on T1- and intermediately T2-weighted images behaved in a distinctive fashion. Active repair tissue could be differentiated from both necrotic bone and normal bone by a tendency for the signal to increase in intensity on intermediately T2-weighted images. These findings suggest that MRI may provide a noninvasive means of quantitatively analyzing the volume and spacial distribution of repair tissue in osteonecrotic femoral heads. In clinical practice, such analysis may lead to improvements in disease staging and treatment planning. PMID- 2317969 TI - Anterior dislocation of the hip associated with fracture of the ipsilateral greater trochanter. A case report. AB - A 22-year-old male motorcyclist fell from a height and sustained an obturator hip dislocation with concomitant fracture of the ipsilateral greater trochanter. The immediate reduction of the dislocation associated with open reduction of the fracture of the greater trochanter showed excellent results at the short-term and long-term follow-up examinations. This extremely rare hip injury seems not to have been previously reported in the literature. PMID- 2317970 TI - Controlled perforation. A safe method of cement removal from the femoral canal. AB - Removal of cement from the femoral canal during total hip revision arthroplasty continues to be very challenging. The technique is described using multiple 9-mm perforations placed at least 5 cm apart on the anterior surface of the femoral shaft. The tip of the revision stem should be at least 5 cm distal to the most distal perforation. From January 1984 to December 1986, 219 cases of revision total hip arthroplasties were performed using this technique; the incidence of ipsilateral postoperative femoral fractures was nine out of 219. Eight of these fractures were at the tip or distal to the femoral prosthesis and were associated with trauma. One fracture occurred through a perforation site and had an associated fracture of the femoral component. This method appears to be a reliable and safe method of cement removal from the femoral canal. PMID- 2317971 TI - Correlation of roentgenographic patterns and clinical manifestations of symptomatic idiopathic osteoarthritis of the knee. AB - A retrospective review of weight-bearing roentgenograms of 2197 knees in 1894 patients with symptomatic idiopathic osteoarthritis (IOA) revealed six different patterns of tibiofemoral deformity. Five of these patterns expand the taxonomic concepts of Ahlback; the sixth, "nonproliferative," was previously undescribed. It was seen exclusively in patients with varus disease and was characterized by a lack of reactive bony changes. Knees with degenerative changes in the medial compartment constituted the majority of cases (63%). The average age of patients was 72 years for those with varus disease, 79 years for those with valgus disease, and 84 years for those with patellofemoral arthritis (PFA). Bilateral involvement was common only in patients with PFA (79%), suggesting a developmental cause for this subset. There was a female predominance in valgus and patellofemoral disease. The authors report here on a classification system of IOA that has been designed and modified to reflect the unique roentgenographic, epidemiologic, and clinical characterization of the six subsets. PMID- 2317972 TI - Acute anterior cruciate ligament reconstruction. Analysis of complications. AB - One hundred fifty-six patients treated with intraarticular anterior cruciate ligament (ACL) reconstruction were analyzed to determine the incidence of complications. The study group of 31 patients (Group I) was treated with repair or reconstruction of an acute ACL injury. A comparison group of 125 patients had reconstruction for chronic ACL instability (Group II). The patients were evaluated clinically and by roentgenograms. The average follow-up time for the study group was 52.2 months. In Group I, 35% developed fibroarthrosis postoperatively that required arthroscopic lysis of adhesions and manipulation to restore motion. In Group II, only 12% developed this complication. However, developing this complication did not affect a patient's long-term clinical result when properly recognized and promptly treated. PMID- 2317973 TI - Load tolerance, security, and failure modes of fixation devices for synthetic knee ligaments. AB - One weak link in synthetic ligament reconstruction of the knee is the fixation device-ligament-bone interface. In this study, a laboratory model using bovine calf bone was designed to evaluate six different fixation devices combined with either an unlooped ligament in different configurations or a looped ligament. Results are expressed in terms of maximum load to failure, elongation at the site of fixation, stiffness of fixation prior to failure, and mode of failure. When failure of the test model occurred, it was always at the ligament--fixation device interface, the fixation device--bone interface, or a combination of the two. Elongation was recorded in all modes of fixation. The most secure fixation was obtained with a cortical screw and a looped ligament, the strength and predictability being mainly dependent on bone quality. The least secure and least predictable fixation was obtained with a prototype called bucket wedge. A barbed ligament staple and an unlooped ligament also had low predictability and considerably less strength than the screw fixation but showed less sensitivity to alterations in bone quality. PMID- 2317974 TI - Arthroscopic debridement of the arthritic knee. AB - Arthroscopic debridement was carried out in 49 knees of 44 patients. These patients, who had a primary diagnosis of arthritis, were older than 50 years of age. Two-thirds had roentgenographic evidence of severe arthritis. Age, weight, compartment location of arthritis, and presurgical range of motion did not affect surgical results. Symptoms of long duration, arthritic severity as evidenced by roentgenograms, and malalignment predicted poor results. Conversely, shorter duration of symptoms, mechanical symptoms, mild to moderate roentgenographic changes, and crystal deposition correlated with improved results. Surgery offered no benefit for 39% of the patients. Another 9% had temporary improvement, averaging 15 months, but were judged failures at the final follow-up examination. Good or excellent results were achieved in 52% of the patients and maintained through the final follow-up examination in 40% of the patients. Of these, two thirds had no visible deterioration within a 33-month average follow-up period. PMID- 2317975 TI - Clinical prognosticators for the efficacy of retinacular release surgery to treat patellofemoral pain. AB - The purpose of this prospective study was to identify clinical, pathologic, and roentgenographic factors that might serve as prognosticators for acceptable results after a lateral retinacular release for treatment of patellofemoral pain unresponsive to conservative measures. Fifty-two knees in 45 patients were studied. The data indicated that acceptable results can be expected in patients who have a negative mal-loose sign (no evidence of patellar malalignment or hyperlaxity) or a positive Sage sign (tight lateral parapatellar soft-tissue structures). Poorer results are predictable in patients with patellar hypermobility. PMID- 2317976 TI - Arthrodesis of the diabetic neuropathic ankle joint. AB - At the authors' institution from 1964 to 1984, ankle arthrodesis was performed in 13 patients with insulin-dependent diabetes mellitus who had a history of ankle sprain or fracture. Nine patients were diagnosed by clinical exam as having a peripheral neuropathy; nine patients had roentgenographic evidence of neuropathic arthropathy prior to surgery. Follow-up study with examination and roentgenograms averaged 42 months. Clinical and roentgenographic union was achieved in seven ankles at an average of 16 weeks. Two patients developed a nonunion, three had an amputation, and one died at two months postoperatively. Thirteen complications occurred in eight of the 13 patients (62%). Twenty reoperations, excluding pin removal, were performed in eight patients (62%). A satisfactory result was achieved in only 50% overall and in only 38% of patients with roentgenographic changes of neuropathic arthropathy. Neuropathic arthropathy contributes to the inordinate complication and failure rates. Ankle arthrodesis should be considered with caution in the diabetic patient. PMID- 2317977 TI - Internal fixation compression arthrodesis of the ankle. AB - Sixteen patients were treated by internal compression arthrodesis of the ankle using cancellous screw fixation. Thirteen patients had a preoperative diagnosis of traumatic osteoarthritis, and three patients had rheumatoid arthritis. All patients were followed until clinical and roentgenographic evidence of union had been obtained (average, 15.1 months). Union was obtained in 15 of 16 cases (94%) by an average of 9.2 weeks. The average ankle evaluation score was 77 points, with 80% of the patients rated good or excellent. Suboptimal results were attributed to technical errors. Midtarsal motion averaged 18 degrees, and subtalar motion was present in the majority of patients after surgery. This technique provides a high union rate while permitting early mobilization of the adjacent hindfoot and midfoot joints with earlier return to satisfactory function. PMID- 2317978 TI - Recurrent osteoid osteoma. Case report with a ten-year asymptomatic interval. AB - Osteoid osteoma has been accepted as a distinct clinical and pathologic entity for more than 50 years. Surgical curettage will often cure the lesion, although en bloc excision is now the preferred treatment. The development of local recurrence after surgery, although rare, has been well documented after both curettage and en bloc excision. Symptomatic recurrence of an osteoid osteoma was seen ten years after surgical curettage. Its occurrence at the same site as the original lesion is consistent with the concept that it had originated from residual tissue and is in keeping with the concept of osteoid osteoma as a benign tumor. PMID- 2317979 TI - Leiomyosarcoma of the popliteal artery. A report of two cases. AB - Leiomyosarcomas (LS) are relatively uncommon soft-tissue sarcomas that occasionally involve the extremities. LS are usually tumors of adults and most often involve the gastrointestinal tract and uterus. When a soft-tissue sarcoma is suspected, comprehensive preoperative staging studies are an important part of the diagnostic and therapeutic management. With the use of computed tomography and magnetic resonance image scanning, the role of the arteriogram in the staging of soft-tissue tumors has been markedly diminished. There is still, however, a place for the arteriogram in the staging of soft-tissue tumors that are proximate to or displace the neurovascular bundle. Two patients demonstrated LS that arose from the popliteal artery, illustrating the importance of arteriography. When indentation and displacement can be visualized, involvement of the artery should be suspected. This may be critical when considering limb salvage versus amputation surgery. If limb salvage surgery is to be accomplished, an interpositional graft and segmental resection of the artery are necessary. PMID- 2317980 TI - Mechanical characteristics of an upper-extremity external fixator. AB - Static and fatigue tests of the small Orthofix unilateral external fixator frame and its main components were performed. The use of six pins increased torsional rigidity, but this configuration failed at lower bending loads when compared to the four-pin configuration, reflecting the uneven holding strength of the pin clamp on three pins. The ball joint maximum torsional resistance was reduced by 27.2%, and the maximum bending resistance was decreased by 35.2% after first failure loading of a fatigue test. The strength of the ball joint returned to the normal level after replacement of the cam and bushing with new components. The locking strength of the fixator body telescoping mechanism was high and did not change during repetitive failure loading. Hence, the fixator should be applied under the four-pin configuration, placing pins in the outer slots of the clamps as recommended by the manufacturer. The frame stability is governed by the performance of the ball joint, and its locking cam should be tightened periodically. If the ball joint locking position starts to migrate from its initial position, the cam and bushing should be replaced. PMID- 2317981 TI - Delayed intramedullary nailing after failed external fixation of the tibia. AB - Thirteen patients (11 males, two females) with 16 tibia fractures (three segmental) were initially treated with external fixation and secondarily had delayed intramedullary nailing after fixator removal. There were six closed injuries and two Grade I, five Grade II, one Grade IIIA, and two Grade IIIB open soft-tissue injuries. The average patient age was 40 years (range, 19-84 years). The external fixator was removed at an average of 12 weeks (range, three to 25 weeks) for malreductions in six case, atrophic segmental fractures in two, and atrophic/unstable fracture patterns in five. Intramedullary nailing was performed at an average of 13 days (range, five to 30 days) after fixator removal. There were 12 reamed nails and one self-broaching nail. Preoperative antibiotics averaged eight days, and postoperative averaged 11 days. All patients healed with bridging callus; full weight bearing occurred at an average of 2.7 months. Follow up evaluation averaged 22.5 months. Weight bearing began within the first three weeks in 12 of 13 patients. Results were rated as excellent in eight and good in five. There were no complications related to infection or non-union. Delayed intramedullary nailing, after excluding potential high-risk patients, is an option for the treatment of tibia fractures that have failed treatment with external fixation. However, it is not recommended as a routine procedure. PMID- 2317982 TI - Ender rods versus external fixation in the treatment of open tibial fractures. AB - This is a retrospective nonrandomized study of 66 open tibial fracture patients that compares comparable population treated at one trauma center. The fractures were treated with either Ender rods or external fixation. Of these, 29 fractures were eliminated from the study due to incomparable variables. Thus, the study group consisted of a total of 37 tibial fractures: 20 treated by Ender rods and 17 treated by external fixation. Open tibial fractures treated with Ender rods had a significantly lower number of complications than those treated with external fixation. The group treated with Ender rods also had a significantly lower number of surgical procedures per patient in Grades I and II open tibial fractures. There were no statistical differences regarding weeks to union or hospital days. Ender rods are superior to external fixation removed early in the treatment of Gustilo's Grades I, II, and IIIA open fractures with either stable or unstable fracture configuration (Orthopaedic Trauma Association Grades IA-IC, IIA-IID, and IIIA-IIIC). Perhaps future study will allow sufficient numbers to determine whether Ender rods can be used in Grades IIIB and IIIC open tibial fractures, but there are no data at this time to support this conclusion. PMID- 2317983 TI - Quantitative roentgenographic densitometry for assessing fracture healing. AB - A noninvasive method was developed to assess fracture healing using optical densitometric methodology. Photometric measurements of osseous tissue density were based on illuminance or intensity of light, transmitted through standard roentgenograms. The method was tested in 6-mm tibial segmental defects and single cut osteotomy defects in adult mongrel dogs. The lowest measureable bone density in the defect was compared to bending rigidity of the involved extremity. For both types of defect, an exponential relationship was found between the densitometric evaluation of the healing fracture gap and bending rigidity. This method proved superior to a roentgenographic scoring method and is capable of detecting small differences in mineral content using standard roentgenograms. The high correlation between densitometric evaluation and bone rigidity indicates this method has potential for use in the in vivo assessment of fracture healing. PMID- 2317984 TI - The pathogenesis of loosening of total hip arthroplasties. The production of factors by periprosthetic tissues that stimulate in vitro bone resorption. AB - The production of factors capable of stimulating bone resorption in the newly formed periprosthetic capsule and in the bone-cement membrane obtained from patients reoperated due to aseptic loosening of cemented total hip prostheses was studied using organ culture techniques. Addition of culture media conditioned by membranes from six patients and bone-cement membranes from two patients to the mouse calvarial cultures resulted in a significantly increased release of calcium. The effect of capsule-conditioned media on calcium release was dose- and time-dependent and significantly reduced by the osteoclast inhibitor of calcitonin. Histologic analysis of bones at the end of the culture period showed that capsule-conditioned media enhanced the breakdown of mineralized bone and increased the number of osteoclasts. The observations showed that newly formed periprosthetic tissues from patients with loose total hip arthroplasties (THAs) can produce one or several factors that stimulate bone resorption in vitro by an osteoclast-mediated mechanism. Not only mechanical failure but also biologic reactions in the periprosthetic tissues eventually lead to osteoclast activation and may contribute to the loosening of THAs. PMID- 2317985 TI - Functional changes in the antagonists after lengthening the agonists in cerebral palsy. I. Triceps surae lengthening. AB - In a recent study, children with spastic cerebral palsy (median age, five years) were examined before and up to a median of 14 months after 52 operations involving elongation of the tendo Achillis or aponeurotomy of the gastrocnemius. On removal of the cast four weeks postoperatively, strength in the dorsiflexors had increased by more than 50%, as evaluated by the ability to raise a weight from a scale. Postoperative function was correlated with preoperative function. Strength had increased more than 200% by 14 months postoperatively, with no instance of excessive lengthening of the triceps. In 13 cases, the dorsiflexors had been without function preoperatively. Two of those cases again lost the dorsiflexor function achieved postoperatively, when dynamic shortening recurred after one year. The study thus confirms the view that antagonist function improves when spasticity in the agonist is reduced by tendon lengthening. PMID- 2317986 TI - Experimental chemonucleolysis with chondroitinase ABC. AB - Chemonucleolysis has recently become an established treatment for intervertebral disc protrusion. However, the exact mechanism of chemonucleolysis is still unknown. If mechanisms of chemonucleolysis include diminution of intradiscal pressure followed by subsequent regeneration of the nucleus pulposus, then a more selective enzyme for glycosaminoglycan, chondroitinase ABC, might be used for chemonucleolysis instead of chymopapain. Thus experimental chemonucleolysis with chondroitinase ABC compared with chymopapain was investigated. In rabbits, chondroitinase ABC is as effective for chemonucleolysis as chymopapain, but the chemonucleolysis process with chondroitinase ABC was milder than with chymopapain. At an early chemonucleolysis phase, chondroitinase ABC action was chiefly limited to digestion of the matrix, and a large number of cells in the nucleus pulposus remained. During long-term observations of chemonucleolysis with chondroitinase ABC, nuclear structure was restored to a nearly normal state. Although limited, this study indicates that chondroitinase ABC might be more suitable than chymopapain for chemonucleolysis. PMID- 2317987 TI - Bone morphogenetic protein. PMID- 2317988 TI - Functional changes in the antagonists after lengthening the agonists in cerebral palsy. II. Quadriceps strength before and after distal hamstring lengthening. AB - In a recent study, 38 patients with spastic cerebral palsy (median age, 5.6 years) were examined before and at a median 13 months after distal lengthening of the hamstrings. Four weeks after operation, the strength of the quadriceps was reduced by a median value of 70%. Seven months after operation, the strength had been regained; by 13 months after operation, it had increased by a median value of 22%. In 20 cases, strength had increased by more than 50%. The present study confirms the theory that quadriceps function is strengthened when the antagonist function is weakened. The study also explains (1) why it often takes six months for gait to become better than before operation and (2) why spasticity of the rectus often increases after the hamstrings are lengthened. PMID- 2317989 TI - Physical therapeutic and surgical management in spastic diplegia. A Japanese experience. AB - With the development of intensive neonatal care, spastic diplegia associated with prematurity has become the most common type of cerebral palsy. The principles of the present authors' treatment for children with the disease are physical therapy (involving neurodevelopmental treatment) and surgical treatment for contractures and deformities. The authors studied the long-term results of physical therapy and its effect on the necessity for surgery and the improvement of locomotor function. From 1973 to 1988, 355 children with spastic diplegia were treated at the authors' facility. From this group, the authors selected and studied 71 children who received systematic treatment for a minimum of one year and who could be followed at the age of six years or older. At the follow-up examination, 41 of these children were free ambulators, 28 were crutch ambulators, and two were not ambulatory. Of the 41 freely ambulatory children, four achieved free ambulation after the age of seven years. Of the 28 crutch ambulators, relatively small hip-flexion contractures were found in 11 children who had received the early developmental treatment program. PMID- 2317990 TI - Surgical treatment of knee dysfunction in cerebral palsy. AB - The prerequisites for normal gait are: (1) stability in the stance phase of gait, (2) clearance of the foot in the swing phase, (3) proper foot preposition in swing, and (4) an adequate step length. In the stance phase, the knee provides shock absorption and energy conservation; in the swing phase, it allows foot clearance. To accomplish these functions, the knee must extend fully in stance and flex approximately 60 degrees in swing. Consequently, balanced muscle action at the hip, knee, and ankle joints, combined with adequate acceleration from the hip flexor and triceps surae muscles, is essential. In the crouch gait of spastic cerebral palsy, hamstring lengthening alone often converts the flexed-knee gait to an extended-knee, stiff-legged gait with inadequate swing-phase knee flexion. This unwanted conversion is due to cospasticity of the quadriceps and hamstring muscles. Restoration of normal knee function in patients with spastic paralysis is more successful when fractional hamstring lengthening is combined with a transfer of the distal rectus femoris tendon to either the iliotibial band or the distal tendon of the semitendinosus. PMID- 2317991 TI - Surgical management of ankle and foot deformities in cerebral palsy. AB - A system of surgical treatment of deformities of the ankle and foot in cerebral palsy is presented on the basis of experience with 420 children. The aim of surgery is prevention or correction of deformities. There are three types of deformity (fixed, dynamic, and mixed), each of which is treated differently. Surgery should be delayed as long as there is functional improvement. The most common indication for foot surgery is equinus deformity, which makes it difficult to keep the heel in the shoe. Tendo Achillis lengthening is satisfactory for fixed equinus, and transfer of the medial belly and the tendon of the gastrocnemius to the dorsum of the foot is appropriate for dynamic equinus. Hindfoot valgus in hypertonic cerebral palsy is treated by peroneus brevis elongation when moderate and in combination with subtalar arthrodesis when severe. Hindfoot valgus in hypotonic cerebral palsy is treated by subtalar arthrodesis only. Hindfoot varus is treated by tibialis posterior lengthening, usually in combination with (1) tendo Achillis lengthening, (2) a Steindler plantar release, or (3) valgus calcaneal osteotomy. Dynamic forefoot supination is treated by split-tibialis anterior tendon transfer or, when associated with dorsiflexion of the hallux, by extensor hallucis longus transfer. PMID- 2317992 TI - Arthrodesis of the metacarpophalangeal joint of the thumb in children and adults. Adjunctive treatment of thumb-in-palm deformity in cerebral palsy. AB - A hypermobile hyperextension or hyperflexion deformity of the metacarpophalangeal (MCP) joint associated with thumb-in-palm deformity in 90 patients affected by cerebral palsy was treated by arthrodesis with or without soft-tissue procedures. Twenty-two of these patients were adults with closed physes, and 68 were children or adolescents with open growth plates. The MCP joint fusion was usually accompanied by intrinsic muscle lengthening and/or extrinsic tendon transfer, but occasionally it was the only procedure performed to diminish the thumb-in-palm position. Even in four-year-olds, joint fusion was a predictable procedure to establish stability of that joint without disturbing longitudinal or circumferential growth. Measurable function was improved to a mild or moderate degree in 44 of the 50 children who were followed to maturity. Eighteen of the 68 children were unavailable for follow-up evaluation. Six of the 50 followed patients showed no functional improvement, although arthrodesis of the MCP joint occurred in four of the six. The other two patients were operated on when they were 12 years of age and developed a fibrous union that was painless and stable when they were adults. Even those patients who had no functional improvement did have improved appearance and easier control of the affected hand when it was manipulated by the opposite hand. The children were followed to maturity with age matched cerebral palsy control patients. There was no significant disturbance in growth of those thumbs that had MCP joint fusion when the physes were open. PMID- 2317993 TI - Indium-111 DTPA flow study to evaluate surgically implanted drug pump delivery system. AB - The authors describe a radionuclide technique for evaluating intrathecal and intraventricular infusions by surgically implanted drug pump delivery systems. Sixteen patients underwent flow studies, performed by injecting 500 mu Ci of indium-111 DTPA into the pumps. Early and delayed images were obtained. These studies enabled distinction among functioning pumps, nonfunctioning pumps, and obstructed or occluded catheters. We conclude that indium-111 DTPA flow studies provide an excellent way to assess these drug pump delivery systems. PMID- 2317994 TI - The effect of projection in esophageal transit scintigraphy. AB - Data from esophageal transit scintigraphy with swallowing of Tc-99m sulfur colloid in water in the supine position were studied to determine the effect of posterior as compared with anterior imaging. Net attenuation was less with the anterior projection. Nonetheless, the posterior projection is favored because of more uniform attenuation. PMID- 2317995 TI - Gallium imaging of esophageal carcinoma: increased sensitivity with lateral views of the thorax. AB - Ga-67 imaging has not been very successful in the detection of esophageal carcinoma. In most reports, sensitivity for the primary tumor ranged from 25-61%, but imaging had been done only in anterior and posterior (A-P) projections. We performed gallium scans in 30 patients with esophageal carcinoma, adding lateral views to the routine A-P projections, to study the effect of lateral views on tumor detection. The A-P views detected only 57% of the tumors while the right lateral visualized 89%, and the left lateral detected 100%. Some lesions may be hidden by the sternum and the spine in the routine A-P views. Previous disappointments with Ga-67 imaging of esophageal carcinoma were probably due to this technical factor. Being gallium-avid, esophageal tumors deserve further studies with this agent to determine the role of Ga-67 imaging in this condition. These studies should be performed with multiple views of the thorax or, better yet, with SPECT imaging of the chest, to circumvent the problem of sternum and spine interference. PMID- 2317996 TI - Adrenal cortical adenoma causing Cushing's syndrome: correct localization by functional scintigraphy despite nonlocalizing morphological imaging studies. AB - A 60-year-old woman with Cushing's syndrome in whom high-dose dexamethasone failed to suppress glucocorticoids was studied by ultrasound and CT. Neither of these morphological studies was interpreted as revealing any adrenal abnormality. Functional imaging with NP-59 (131-I-beta-iodomethylnorcholesterol) revealed unequivocal, intense, unilateral uptake in the left adrenal gland and subsequent surgery removed a 2.5 cm adrenocortical adenoma from this site. Following surgery the patient was temporarily adrenocortically insufficient but later returned to normal. It is unusual for adrenocortical adenomas causing Cushing's syndrome not to be correctly located by CT. NP-59 scintigraphy in addition to being highly accurate in the location of adrenocortical adenomas also has the advantage of correctly depicting bilateral cortical nodular hyperplasia in which CT will frequently reveal only the largest nodule, which may be incorrectly designated a unilateral adenoma. Furthermore, scintigraphy provides evidence of suppression of the contralateral, normal adrenal cortical tissue in Cushing's syndrome caused by an adrenal adenoma and predicts the vulnerability of such patients to postoperative adrenocortical insufficiency. PMID- 2317997 TI - Role of fast data acquisition method with Tc-99m HMPAO brain SPECT in patients with acute stroke. AB - The first data acquisition method for Tc-99m hexamethylpropyleneamineoxime (Tc 99m HMPAO) brain SPECT was used in two patients with acute stroke 5 and 8 hours after the event. In one patient Tc-99m HMPAO fast SPECT showed perfusion defects before the same was manifested on CT. In the other patient, Tc-99m HMPAO fast SPECT showed larger defects than the edema seen on CT. The Tc-99m HMPAO fast SPECT might be feasible for the evaluation of acute stroke patients. Since the time required for fast SPECT is much shorter than usual SPECT, it appears to be more suitable for some patients with acute stroke who are brought to the hospital in a very critical condition. PMID- 2317998 TI - Tc-99m HMPAO SPECT of the brain in the neonate. AB - A brain scan with Tc-99m hexamethylpropyleneamineoxime (HMPAO) performed on a neonate demonstrated normal localization only in the sensorimotor cortex, basal ganglia, and cerebellum. This pattern of localization is remarkably similar to previously published PET images of the neonate. Because Tc-99m HMPAO is readily available and has biochemical and physical characteristics that are suitable for perfusion imaging of the brain, it likely will become a major imaging agent in nuclear medicine. Normal scan findings in the neonatal age group with Tc-99m HMPAO have not been previously reported because of limited clinical use to date. PMID- 2317999 TI - Technetium-99m HMPAO imaging in Sturge-Weber syndrome. AB - The Tc-99m HMPAO brain imaging confirmed marked hypoperfusion secondary to anomalous cerebral venous drainage of the Sturge-Weber syndrome. Until now, this had been a hypothesis suggested by results obtained from conventional brain scans and cerebral arteriography. PMID- 2318000 TI - The value of urine creatinine analysis in the evaluation on Schilling tests. AB - We performed a prospective study to assess the clinical value of evaluating the adequacy of 24-hour urine specimens submitted for Schilling tests. A total of 121 specimens were evaluated of which 51 had abnormal vitamin B12 excretion values. Of those 51, there were 23 with apparently inadequate total creatinine content (implying a collection of less than 24 hours). Six of 12 specimens with less than 600 ml had adequate total creatinine content as well as normal vitamin B12 excretion. Compared with evaluation of specimen volume alone, these data support the inexpensive urine creatinine assay as a valuable source of information regarding the adequacy of 24-hour urine collections thereby improving the specificity of the Schilling test. PMID- 2318002 TI - Scintigraphic demonstration of ectopic autonomously functioning thyroid adenoma with normal cervical thyroid. PMID- 2318001 TI - Lung uptake on Tc-99m albumin colloid liver spleen scan and on Ga-67 scan in angiotropic lymphoma. AB - Lung uptake of Tc-99m sulfur colloid has been reported in various hepatic and extrahepatic diseases, and lung uptake of gallium-67 may occur in patients with various interstitial lung disease without radiographic abnormality. This may be the first case of Tc-99m albumin colloid and Ga-67 lung uptake in a patient with angiotropic lymphoma of the liver, spleen, and uterus. PMID- 2318003 TI - Detection of metastatic thyroid carcinoma on renal dynamic study. PMID- 2318004 TI - Gallium scan diagnosis of sarcoidosis in the presence of equivocal radiographic and CT findings: value of lacrimal gland biopsy. PMID- 2318005 TI - Pelvic bone imaging in bladder exstrophy. PMID- 2318006 TI - Iliac artery aneurysm causing ureteric obstruction. PMID- 2318007 TI - Spinal compression fractures demonstrated on renal scan. PMID- 2318009 TI - Stimulation and the preterm infant: the limits of plasticity. PMID- 2318008 TI - Prediction of drug distribution into human milk from physicochemical characteristics. AB - Decisions about the safety of breast feeding during maternal ingestion of drugs require knowledge of the amount of drug which might be present in the milk. For many drugs this has not been studied, and mothers are usually advised against breast feeding. In many cases this is undoubtedly unnecessary, as the total dose to which the baby is exposed is often negligible. It would be very helpful, therefore, to be able to predict the approximate amount of drug which might be present in milk. Existing theory of pH partitioning enables estimation of the distribution of unbound drug, i.e. milk: plasma unbound ratios. However, these ratios are poor estimates of the concentration ratios for whole milk, because whole milk contains proteins and lipid in which drugs will distribute in amounts which depend on their particular physicochemical properties. To predict the milk: plasma concentration ratios for whole milk the amount of drug present in the protein and lipid phases must be considered along with the unbound drug distribution. A 'phase distribution model' has therefore been developed which permits estimation of whole milk: plasma concentration ratios. The model requires a knowledge of the unbound drug concentration ratio, the plasma and milk unbound fractions and the milk lipid: ultrafiltrate partition coefficient. Evaluation of the model by comparison of predicted whole milk ratio values with literature milk: plasma area under the curve (AUC) ratios indicated a trend to overprediction for acidic and neutral drugs and underprediction for basic drugs. Transformation of the phase distribution equation by taking logarithms results in a relationship which can be analysed by multiple linear regression to derive predictive equations for acidic and basic drugs which take into account the relative contributions of each component of the model. Regression of the logarithms of the literature milk: plasma AUC values against the independent variables resulted in good correlations for acidic and basic drugs. The independent variables explained 93.1% and 82.9% of the variance in the values for acidic and basic drugs, respectively, with random scatter of residuals. The equations, together with those to predict unbound fractions of drug in milk and milk lipid: ultrafiltrate partition coefficients, enable the ratio of the milk: plasma AUCs to be estimated for any acidic or basic drug for which the distribution into human milk is not known, using the pKa, octanol: water partition coefficient and plasma protein binding values of the drug. The data set for neutral drugs (n = 3) was too small to develop a correlation equation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2318010 TI - Guidelines for stimulation with preterm infants. PMID- 2318011 TI - Handling preterm infants in hospitals. Stimulating controversy about timing of stimulation. AB - The authors' research draws from a primary concern for the effects of the animate and inanimate caregiving environment on brain growth and central nervous system organization in hospitalized preterm infants. The current report presents data on physiologic trends in preterm infant heart rate and oxygenation as related to the timing and content of caregiver stimulation, specifically medical and social forms of touch. Results indicate that while most instances of bradycardia were not closely preceded by tactile stimulation, prebradycardia periods, which included touch, had lower pO2 levels than did baseline periods that included touch. These findings suggest that medical or "developmental" tactile stimulation presented when the infant was already physiologically compromised (with low pO2) may potentiate an underlying vulnerability to bradycardia. Timing, versus type, may be the better predictor of the physiologic effect of caregiver interventions on preterm infants. PMID- 2318012 TI - Behavioral responsivity in preterm infants. AB - Both prematurity and the type and degree of perinatal complications affect behavioral responsivity. Decreased sociability and decreased soothability shown by preterm infants can be considered to be attributable to some stress on the central nervous system. Because marked individual differences are observed within preterm groups, stimulation should be geared to the individual's level of responsivity. PMID- 2318013 TI - Protective apathy, a hypothesis about the behavioral organization and its relation to clinical and physiologic status of the preterm infant during the newborn period. AB - This article describes the behavioral organization and its change in relation to physiologic and clinical variables in a group of infants whose birthweight was less than 1.5 kg and who were experiencing and recovering from acute cardiorespiratory illness. The authors used the Brazelton Premature Sale, which was designed for use with a wide range of gestational ages (27 to 35 weeks). Examinations began 1 week after birth and were obtained serially during the initial recovery period of these infants. PMID- 2318014 TI - Behavioral and psychophysiologic assessment of the preterm infant. AB - Cardiorespiratory activity was recorded during attentional responsivity on the Brazelton scale in term and preterm infants. Preterm infants showed less heart rate deceleration, less heart rate variance and less power in the ECG spectrum at frequencies associated with respiratory sinus arrhythmia and oscillations in blood pressure: A lower threshold for attentional stimulation in the preterm infant may trigger a CNS mechanism that protects the infant from stimulus overload. Study of the coordination between behavioral and physiological reactivity provides an understanding of the role of the CNS in mediating information processing. PMID- 2318016 TI - Comparison of plasticity in sensory and cognitive processing systems. AB - The term "brain plasticity" can be applied to a number of processes, each with its own set of complex mechanisms. The plasticity of the human brain during postnatal development has been contrasted for a sensory, i.e., auditory, and cognitive system by comparing the development of two different evoked potential components. The short-latency auditory brainstem responses (ABRs), which are generated by auditory neurons within the brainstem auditory pathway, are mature by 1 to 2 years after birth. The rate of ABR development, as shown by longitudinal recordings from preterm infants, appears to be equally rapid in intrauterine and extrauterine environments. In contrast, the long-latency P300 cognitive potential, which reflects such processes as sequential information processing and short-term memory, does not show a mature waveform and latency until 14 to 17 years of age. This protracted rate of development cannot yet be related to a brain substrate, as the generator origins of the P300 are unknown. Clinical and animal data suggest, however, that limbic structures are critically involved. The long developmental history of the P300, in contrast to the ABRs, provides a functional measure of developmental plasticity in a cognitive versus a sensory brain system. PMID- 2318015 TI - The Mother-Infant Transaction Program. The content and implications of an intervention for the mothers of low-birthweight infants. AB - A brief, economic neonatal intervention based on the transactional model of development and influenced predominantly by the conceptual design of the Neonatal Behavioral Assessment Scale was implemented in an intensive care nursery with the mothers of a group of low-birthweight infants. The development of the intervention group was compared with that of a similar group of low-birthweight infants who did not receive the intervention and contrasted with that of a group of normal-birthweight infants. The intervention had a significant effect on maternal adjustment and perception of the infant at 6 months. No significant effect on infant cognitive development was apparent until 36 months (that is, 31 months after the intervention had ceased). The intervention effect was even more significant at 48 months. It appeared that the two low-birthweight groups had progressively diverged after 12 months, the intervention group rising until it approximated the normal-birthweight group in cognitive development, whereas the low-birthweight control group deteriorated. The economical nature of the MITP, its unique (although delayed) benefits, and the apparent durability of the intervention effect, suggest that this intervention program has important theoretical and practical implications and potentially far-reaching applications. PMID- 2318017 TI - Brain plasticity after damage. AB - This is a brief summary of our research on the prevention or reduction of the effects of brain damage. I believe that the results contain a number of exciting promises. At this time, the greatest hope for effective remedial interventions comes from the choline and metyrapone studies. However, I am also reminded of the components a psychiatrist who worked with children in the heart of Philadelphia made some 20 years ago at a conference on mental retardation. He said that the most significant contribution to the elimination of mental retardation in his city would be the elimination of lead-based paints from the walls of ghetto apartments, an intervention second only in effectiveness to the elimination of the ghettos themselves. The importance of early interventions with individuals suffering brain damage, either general or specific, is clearly recognized. In research now well underway, Yong Shen, William Smotherman, and I have found encouraging results indicating that both short- and long-term effects of hypoxia induced by clamping the rat's umbilical cord can be attenuated by the prior administration of a calcium L channel antagonist. If those results are upheld in further studies, the principles of prevention of damage described in this article for the adult may prove to be even more potent in the young. PMID- 2318018 TI - Plasticity triggering experiences, nature, and the dual genesis of brain structure and function. AB - Mammalian brains are capable of powerful adaptive and plastic potential. Because of this, the central nervous system can cope with an ever-changing environment. This short review details some of the experiments performed on the visual cortex, exactly these adaptive capabilities. PMID- 2318020 TI - Common soft tissue tumors. PMID- 2318019 TI - Development and plasticity of the primate cerebral cortex. AB - The results of our studies of corticocortical connectivity in developing monkey association cortex contrast with those obtained in similar studies of sensory regions in other species. In association areas of the monkey, these connections emerge very early in development, and many of the details of their organization are well specified from their earliest appearance. The presence of an adultlike pattern of organization a full month before birth suggests that these events probably are determined in large part by forces independent of general environmental stimulation, unlike the pattern seen for sensory regions in the cat. Do these differences reflect variations between species or between the development of sensory and nonsensory regions of the cortex? The answer is probably both. Our results suggest that diverse areas of the brain may differ in the extent to which they respond to environmental influences. For example, many of the organizational features that apparently emerge from an initially diffuse organization in sensory areas appear to be more strictly specified in their initial formation in the prefrontal cortex. However, we should not rule out the possibility that many of the features of connectional organization that are responsive to the environment in the sensory areas (e.g., the distribution of corticocortical neurons) develop in the prefrontal cortex during the prenatal period and therefore may simply be buffered from the effects of environmental stimuli. In addition, many aspects of the circuitry of the prefrontal cortex clearly continue to develop well into the postnatal period and may be subject to modification by experience. Among these are the organization and density of synaptic contacts and the elaboration of dendritic surfaces. Although relatively little is known concerning the response of these features to stimulation in the prefrontal cortex, studies from sensory areas suggest that these may be good candidates for modification by external interventions. The text of this paper was taken from a presentation given at the 1986 Johnson and Johnson Pediatric Roundtable. In the period between the original talk and the publication of this article, several studies have emerged on the development of corticocortical connectivity in sensory cortical regions of nonhuman primates. In agreement with our data in the monkey prefrontal cortex, these studies have also found that the distribution of callosal neurons in the somatosensory and visual cortices is adultlike at least 1 month prior to birth.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2318021 TI - Amikacin pharmacokinetics in a patient with spinal cord injury. PMID- 2318022 TI - Treatment of suspected postcholecystectomy diarrhea with psyllium hydrophilic mucilloid. PMID- 2318023 TI - Sympathetic activation during the cold pressor test: influence of stimulus area. AB - The purpose of this study was to determine the effect of the size of the stimulus area on the muscle sympathetic nerve activity (MSNA), systolic arterial blood pressure (SAP), and heart rate responses to the cold pressor test. To accomplish this, these variables were measured before (control), during, and after 1.5 min of ice water immersion of either one or both hands in nine healthy subjects (aged 19-27 years). The cold stimulus elicited significant increases above control levels in all three variables under both conditions (P less than 0.05). Immersion of both hands produced a much greater increase in total MSNA (+366%) than immersion of a single hand (+187%) (P less than 0.05). However, the magnitudes of the increases in SAP and heart rate during two-hand immersion (29 +/- 6 mmHg and 10 +/- 2 beats min-1) were not significantly different from the responses during the one-hand trials (24 +/- 5 mmHg and 6 +/- 2 beats min-1, P greater than 0.05). There was a strong, direct relationship between total MSNA and SAP responses during one-hand immersion (r = 0.93, P less than 0.001) but not during immersion of both hands (r = 0.66, P = 0.08). These findings indicate that during the cold pressor test the magnitude of the increase in sympathetic discharge to skeletal muscle, but not the systolic blood pressure response, is influenced by the size of the tissue area exposed to the stimulus. PMID- 2318024 TI - The effect of sympathetic blockade and cooling in Raynaud's phenomenon. AB - Nineteen patients with Raynaud's phenomenon (12 suffering from generalized scleroderma [GS] and seven from primary Raynaud's phenomenon [PR] and seven cold tolerant healthy women underwent a cooling challenge with combined body and finger cooling. Finger systolic blood pressure was measured at 30 and 15 degrees C, before and after nervous blockade at the finger-base with lidocain. Finger/arm blood pressure ratio (FBP/armBP) at 30 degrees C was significantly lower in GS as compared to controls and PR, and it did not change after nervous blockade in any group. FBP/armBP at 15 degrees C, decreased to zero in all patients with Raynaud's phenomenon and to median 0.67 in controls, prior to nervous blockade. After nervous blockade, in response to cooling, FBP/armBP at 15 degrees C decreased significantly and was comparable in all groups. We conclude that the sympathetic nervous system seems to play an important part in provoking Raynaud's phenomenon in PR and most GS. PMID- 2318025 TI - A non-invasive approach to cardiac autonomic neuropathy in patients with diabetes mellitus. AB - The purpose of this study was to obtain information regarding the participation of the sympathetic nervous system in cardiac autonomic neuropathy in patients suffering from diabetes mellitus employing spectral analysis of heart rate variability in the supine and standing posture. Ten insulin-dependent diabetic patients (29 +/- 2 years) with a short to moderately long duration of diabetes (11 +/- 1 years) and cardiac vagal neuropathy based on measurements of respiratory sinus arrhythmia were compared to 10 healthy volunteers (27 +/- 1 years) before and after the administration of atropine and atropine plus propranolol. In diabetic patients the reactivity in total power (delta TP) from supine to upright position was significantly lower compared to control subjects before and after atropine. There was no significant difference in delta TP between diabetics and controls after atropine plus propranolol. The magnitude of TP increase is essentially due to the increase of blood pressure related heart rate fluctuations (delta MF) from lying to standing and dependent on beta adrenergical efferent activity to the heart. In diabetic patients as well as in normal subjects under the influence of atropine plus propranolol the delta MF power was significantly lower compared to the unmedicated control and atropine group. There was no significant difference between diabetics and controls after combined autonomic blockade. It was concluded that delta MF heart rate spectral power could serve as an indirect, non-invasive, quantitative and sensitive marker of early cardiac sympathetic damage. PMID- 2318026 TI - Influence of local beta-adrenoceptor blockade on exchange of fat and glucose in the human leg after surgery. AB - The metabolic effects of the local administration of propranolol were determined in seven patients undergoing cholecystectomy. Measurements were carried out in the early postoperative period before and after infusion of 2 mg of intraarterial propranolol into the femoral artery of one leg using the other leg as control. Blood flow and arterio-venous concentration differences for oxygen, glucose, lactate, alanine, glycerol and total FFAs were determined. Uptake and release of FFAs were determined by using a tracer technique. The statistical analyses were based on differences between the test and the control leg in changes following the blockade. Glycerol release was significantly more suppressed in the test leg than in the control leg. No difference between the legs was seen in the uptake of oxygen, FFA and glucose or the release of lactate and alanine. The arterial concentration of propranolol was 6.07 +/- 0.72 ng ml-1 (mean +/- SEM). This study indicates that a local beta-blockade by intra-arterial propranolol infusion after surgery slightly reduces the postoperative lipolysis in leg tissues but does not influence or only marginally influences leg blood flow and oxygen uptake or the exchange of glucose, lactate and alanine after moderate surgical trauma. PMID- 2318028 TI - Neuropeptide Y is released together with noradrenaline from the human heart during exercise and hypoxia. AB - The myocardial release of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline (NA) during exercise with and without arterial hypoxia was measured in 18 healthy men by arterial (a) and coronary sinus (cs) catheterization. Exercise was performed in the supine position on a cycle ergometer at a load, selected to produce a heart rate during air breathing of 120 beats min-1. Coronary sinus blood flow (CSBF) was measured and a and cs samples for NPY-LI, NA, oxygen and lactate analyses were taken at rest and after 6 min exercise. The inspiratory gas was then switched to 15% (n = 8) or 12% (n = 10) oxygen in nitrogen, exercise continued at the same load and measurements repeated after 6 min. At rest no significant release and during normoxic exercise a very small myocardial release of NPY-LI and NA was detected. During hypoxia compared to normoxia the cardiac NPY-LI release increased four-fold and the NA net release doubled at the same time as the arterial NPY-LI remained unaltered or only slightly increased. Both the NPY-LI and the NA net release from the heart correlated with the heart rate and the arterial but not the cs oxygen tension. The NPY-LI release was correlated with the NA net release. The findings suggest that arterial hypoxia stimulates cardiac NPY together with NA release which derives from local sympathetic nerves. The release from the heart seems to be greater than from other tissues. PMID- 2318027 TI - Dissociation between vascular and metabolic effects of nicotinic acid in Gilbert's syndrome. AB - The relationship between the vasodilating and the hyperbilirubinaemic effect of low and high doses (50 and 300 mg i.v.) of nicotinic acid was studied in baseline conditions and after indomethacin pretreatment in healthy controls and patients with Gilbert's syndrome (a condition characterized by fluctuating, nonhaemolytic unconjugated hyperbilirubinaemia). The hyperbilirubinaemic effect of nicotinic acid was confirmed to be more pronounced in Gilbert's syndrome patients than in controls. The magnitude of hyperbilirubinaemia in the two groups was not dependent on the dose of nicotinic acid or indomethacin pretreatment. A dose dependent vasodilation which was inhibited by indomethacin could be demonstrated in both controls and Gilbert's syndrome subjects. Vasodilating properties of nicotinic acid were therefore found to be dissociated from the effect on bilirubin. PMID- 2318029 TI - Lung function in patients with prior poliomyelitis. AB - Lung volumes and spirometric flows, maximal respiratory pressures, lung diffusion capacity and blood gases were evaluated in 20 patients with prior poliomyelitis and compared with data from an age- and sex-matched control group. In the polio patients, static lung volumes and pulmonary flow capacity were significantly reduced to approximately 65% of the values of the control group. However, expiratory and inspiratory flows were normal in relation to lung volumes, while maximal respiratory pressures were significantly reduced in the polio patients. Static lung volumes and forced flows were correlated with the maximal respiratory pressures both in the polio patients and in the controls. However, when the muscle force in the polio patients decreased below a certain level, it became more important as a determinant of lung-flow capacity. The polio patients had a significantly increased PCO2 but a normal oxygen saturation and PCO2 was inversely correlated with the maximal respiratory pressures in the patients but not in the controls. The lung diffusion capacity was reduced in the polio patients compared to the controls, but less markedly than vital and total lung capacity. The findings indicate a restrictive respiratory dysfunction and alveolar hypoventilation most probably due to weakness of the respiratory muscles. PMID- 2318030 TI - Indications for allergen immunotherapy during pregnancy. AB - Allergen immunotherapy has been proven to be an efficacious and valuable tool in the treatment of the allergic patient with perennial rhinitis who is intolerant of medications or has moderate to severe asthma. It may also be useful for the allergic pregnant patient to reduce the severity of asthma or rhinitis, and possibly to prevent the complications of severe asthma. It may reduce the use of other medications that are undesirable during pregnancy. Allergen immunotherapy has been shown to be safe for both the mother and fetus during pregnancy. It does not need to be stopped during pregnancy, but the maintenance dose should be modified. Immunotherapy plays an important role in the treatment of severe allergic disease by virtue of its capacity to reduce airway hyperresponsiveness and late-phase airway responses that lead to inflammation and chronic symptoms. PMID- 2318031 TI - Causes, diagnosis, and management of toxic epidermal necrolysis. PMID- 2318032 TI - Pathology, pathogenesis, and possible causes of polymyositis. PMID- 2318033 TI - Diabetes. A view from the inside. PMID- 2318035 TI - 'I'll get nurse to do it'. PMID- 2318034 TI - Contraception for the young. PMID- 2318036 TI - The person with diabetes. PMID- 2318038 TI - Traumatic disruption of the suspensory apparatus in foals. AB - Traumatic disruption of the suspensory apparatus is a catastrophic injury in the horse. Although this injury has been described in the adult, little information is available in the foal. This paper describes 3 foals with metacarpophalangeal joint instability caused by traumatic disruption of the suspensory apparatus. Two foals had biaxial proximal sesamoid fractures in a single forelimb, and 1 foal had avulsion of the distal sesamoidean ligaments in 1 forelimb plus biaxial proximal sesamoid fractures in the other forelimb. The foals with single forelimb involvement were managed with splints, and the foal with bilateral disruption of the suspensory apparatus was euthanatized. Both treated foals resumed natural exercise at pasture. Both continue to be pasture sound 2 and 3 years after injury and are to be used for breeding. Management of disruption of the suspensory apparatus causing metacarpophalangeal joint instability using external support was effective for salvage of these 2 valuable foals for breeding. PMID- 2318037 TI - Deficiency of uridine monophosphate synthase among Holstein cattle. PMID- 2318039 TI - Intracranial schwannoma in a horse. AB - A case of intracranial schwannoma is described in a young horse. Clinical signs developed slowly and were suggestive of a lesion involving the left cerebrum. The filly exhibited a change in mentation, and circled to the left. Visual impairment and decreased facial sensation were noted on the right side. A solitary schwannoma which compressed the left cerebrum was found at necropsy. PMID- 2318040 TI - Comparison of the effects of an isosmolar and hyperosmolar oral rehydrating solution on the hydration status, glycemia and ileal content composition of healthy neonatal calves. AB - Isosmolar oral rehydrating solutions (ORS) used to treat diarrheic calves are low in energy. In contrast, hyperosmolar ORS may have a dehydrating effect. This study was designed to compare the net water and glucose absorption from the small intestine of normal calves given isosmolar or hyperosmolar ORS. Six calves were used for the experiment. A reentrant ileal cannula was implanted surgically. Each calf was fed with either the isosmolar or the hyperosmolar solution. The next day, the second solution was given. Both contained chromium EDTA as a nonabsorbable marker. Changes in the hematocrit, total plasma protein, plasma osmolality, plasma glucose concentration, and ileal volume, osmolality, glucose content, and chromium concentration were monitored for 10 hours. The only statistically significant difference was in the post-feeding plasma glucose level: it peaked at the higher level (p less than 0.05) in calves fed the hyperosmolar solution. In normal calves, the hyperosmolar ORS had no effect on the hydration or on the small intestinal fluid composition. PMID- 2318041 TI - Pseudohyperparathyroidism in a mare associated with squamous cell carcinoma of the vulva. AB - An 18-year-old Appaloosa mare was examined because of squamous cell carcinoma of the vulva, anorexia with pronounced weight loss, and hypercalcemia. The tumor had developed rapidly over a period of 3 months and externally extended ventrally involving the perineum and the dorsal aspect of the udder. Necropsy examination demonstrated a large primary squamous cell carcinoma of the vulva, perineum, and mammary gland with metastases to the supramammary, sublumbar, deep inguinal, and mediastinal lymph nodes. No gross renal lesions were observed and, histologically, there was only mild vacuolation of renal tubular epithelium. Based on the normal concentration of serum parathyroid hormone, the absence of evidence of hypervitaminosis D, and normal renal function, a diagnosis was made of hypercalcemia of malignancy or pseudohyperparathyroidism. The mechanism responsible for hypercalcemia was not determined, but the histologic type of the neoplasm and the clinical course suggested possible production of a humoral hypercalcemic factor by the neoplasm, similar to that demonstrated in certain types of human squamous cell carcinoma. PMID- 2318043 TI - Seasonal flank alopecia in ovariohysterectomized dogs. AB - Recurrent seasonal flank alopecia was recognized in 5 ovariohysterectomized female dogs. The dogs first developed hair loss between 1 1/2 and 4 1/2 years of age. The hair loss began in March or April (spring) and spontaneously resolved in July or August. The dogs were otherwise healthy, and no cause for the condition could be determined. PMID- 2318042 TI - Hypoperfusion of the small intestine during slow infusion of a low dosage of endotoxin in anesthetized horses. AB - The effects of intravenous infusion of endotoxin for 30 minutes at a cumulative dosage of 0.03 micrograms/kg on average carotid arterial pressure, and on average arterial pressure, capillary pressure, venous pressure, total vascular resistance, precapillary resistance, postcapillary resistance, and capillary filtration coefficient in the jejunum were compared to the effects of intravenous infusion of 0.9% sodium chloride solution in 6 anesthetized horses. Endotoxin significantly reduced intestinal venous blood flow by inducing vasoconstriction. Increased vascular resistance resulted from increased precapillary resistance. The capillary filtration coefficient was unchanged by endotoxin. These results suggest that intestinal vasoconstriction occurs during the compensatory stages of endotoxemia. PMID- 2318044 TI - Early embryonic death in lambs induced by Veratrum californicum. AB - Both field and laboratory observations have suggested the possibility of embryonic death from 14th day ingestion of Veratrum californicum by pregnant sheep. An experiment was conducted to tabulate the incidence of embryonic death from 14th day ingestion of high doses of plant material. Six of eight ewes so dosed were non-pregnant at term (75%), compared to none in controls, and were, therefore, believed to have experienced embryonic death from the plant ingestion. Results suggest that ingestion of plant material could account for many open ewes at lambing time in ranching operations where Veratrum has been ingested in early gestation. PMID- 2318045 TI - Hemolytic potential of guaifenesin in cattle. AB - The hemolytic effect on bovine red blood cells of 5%, 10%, and 15% guaifenesin solutions in 5% dextrose, 0.9% saline (NaCl), or distilled water was determined in vitro at 2 plasma concentrations (250 micrograms/ml, 500 micrograms/ml). A solution of 5% guaifenesin in a 5% dextrose solution or 5% guaifenesin in 0.9% saline produced minimal hemolysis in vitro. The amount of hemolysis of bovine red blood cells in vitro was related to the concentration of guaifenesin, diluent (5% dextrose, 0.9% NaCl, distilled water) and the plasma concentration of guaifenesin. In addition, plasma hemoglobin was determined in 4 adult dairy cows following the IV administration of 5% and 10% guaifenesin. These studies suggest that a solution of 5% guaifenesin in 5% dextrose is the most suitable solution for clinical use in cattle. PMID- 2318046 TI - Early prediction of outcome from cerebral trauma by somatosensory evoked potentials. AB - The prognostic value of short-latency somatosensory evoked potentials (SEP) during the first 4 days after severe head injury was studied in a group of 100 ICU patients. There was a strong association between the presence of bilateral cortical potentials and a good recovery or moderate disability 6 months after injury. In contrast, the bilateral or unilateral absence of cortical potential was associated with severe disability, persistent vegetative state, or death in a high percentage of patients. A reliable prediction of outcomes was obtained from SEP recorded within 24 h of head injury. Predictive accuracy was not influenced by the time of recording or cumulative analysis of consecutive daily SEP over the first 4 days after injury. Short-latency SEP can provide a reliable and accurate prognosis for sedated and curarized patients, and can have an important role in the management and triage of patients with severe head injury who are undergoing intensive therapy. PMID- 2318047 TI - Oxygenation index in patients with meconium aspiration: conventional and extracorporeal membrane oxygenation therapy. AB - The use of the alveolar-arterial oxygen difference P(A-a)O2 and the oxygenation index (mean airway pressure [Paw] FIO2 x 100/PaO2) have been proposed for selecting infants who will require extracorporeal membrane oxygenation (ECMO) therapy. However, the use of the oxygenation index (OI) in conjunction with Paw in an exclusive population of patients with meconium aspiration syndrome (MAS) has not been reported. Fourteen patients born in our facility and managed with conventional therapy and five infants treated with ECMO were enrolled in the study. All patients had clinical and x-ray evidence of MAS. Infants who received conventional treatment required mechanical ventilation greater than 48 h, FIO2 1.0, and were under the care and supervision of one neonatologist. Management was directed to minimize barotrauma by avoidance of routine hyperventilation, use of lower Paw, and sufficient expiratory time. One patient died before ECMO and 13 infants survived. Six survivors had an OI greater than 25 (three had an OI greater than 40), six had a Paw greater than or equal to 12 cm H2O (12 to 15 cm H2O in five infants) and six patients had a P(A-a)O2 greater than or equal to 610 torr. One surviving infant was transferred for ECMO therapy (OI 67, Paw 20 cm H2O). The five patients treated with ECMO survived (OI 48 to 92, Paw 20 to 29.5 cm H2O P(A-a)O2 627 to 650 torr). One patient in each group developed chronic lung disease with evidence of resting tachypnea. Our findings indicate that an OI greater than 40 in association with a Paw greater than or equal to 20 cm H2O may be helpful in predicting which infants with MAS need ECMO, whereas patients requiring a Paw less than or equal to 15 cm H2O can be managed with conventional therapy. An OI greater than or equal to 25 but less than 40 is not associated with high mortality in these patients. The predictive value of Paw of 16 to 20 cm H2O and the duration of an OI greater than 40 in patients with MAS need further investigation. PMID- 2318048 TI - Early nosocomial infections in pediatric cardiovascular surgery patients. AB - All patients undergoing cardiovascular surgery between July 1, 1987 and February 29, 1988 were followed from admission to the pediatric ICU (PICU) daily by an intensivist/anesthetist. Patients were characterized by surgical procedure and PRISM score on ICU admission. Of 310 patients, 40 patients (nosocomially infected patient ratio 12.9) developed 78 infections (nosocomial infection ratio 25.2), of which 28% (n = 22) were wounds, within 2 months of surgery. Early wound infection followed 8% of closed, nonpump cases and 6.7% of open, pump cases. Wound infection was more likely if the sternum was open on the ward (elective or emergency) (27.6% open vs. 5.0% closed, p less than .001) or if the PRISM score was greater than or equal to 10 on PICU admission (10.7% greater than or equal to 10 vs. 2.3% less than 10, p less than .01). The causative agents in wound infections in closed cases were Staphylococcus aureus (70%) and coagulase negative staphylococci (CONS) (30%) while in open, pump cases the agents were CONS (33%), Pseudomonas aeruginosa (27%), Candida spp. (27%), and S. aureus (20%). Nonwound infections accounted for 72% of infections (n = 56). The number of bacteremias and other central and arterial line-related infections approximated wound infection in incidence at 6.8/100 patients. Wound infections are more likely if the sternum has been left open on the ward, if the patient has a high PRISM score on PICU admission, and after specific surgical procedures. PMID- 2318049 TI - Gastric secretion pH measurement: what you see is not what you get! AB - We evaluated the accuracy of gastric secretion pH measurements as performed in three ICUs. The pH of 275 samples was measured with pH paper using established techniques. The pH of 85 additional samples was determined with a hand-held pH meter. All specimens also were measured using a research laboratory pH meter to learn the true pH. Analyses included mean and SD of the difference between the two measurements, the correlation coefficient (r value), and the concordance correlation coefficient. The pH meter values disagreed significantly with pH paper measurements. Measurements of gastric secretion pH with pH indicator paper do not guide therapy reliably. Inaccurate values derived from pH paper measurements could have resulted in inappropriate treatment in 28% of the samples tested. A portable, battery-powered pH meter accurately reproduced laboratory pH meter measurements and is a reasonable device for clinical use. PMID- 2318050 TI - Axillary or internal jugular central venous catheterization. PMID- 2318051 TI - Effect of exogenous surfactant on the development of bronchopulmonary dysplasia in a baboon hyaline membrane disease model. AB - To test the effect of exogenous surfactant on the evolution of histopathologic changes of bronchopulmonary dysplasia (BPD), we conducted a study in a premature baboon hyaline membrane disease model. One hundred mg/kg bovine surfactant sonicated in saline or 3 ml/kg saline placebo was instilled via the trachea at about 10 min of age. The clinical status and physiologic changes were monitored for 9 days, and pulmonary histopathology was evaluated after death. Compared to the control, the surfactant-treated animals showed a significant improvement in arterial/alveolar oxygen ratio and pulmonary compliance, facilitating rapid weaning from assisted ventilation. Lung histology revealed that pulmonary parenchyma expanded 70% to 95% without features of early BPD. Dysplastic maturation, air trapping, or cellular atypia was not seen. In contrast, lung histology in the control group revealed alveolar expansion less than or equal to 50%, basal cell hyperplasia in the bronchial and bronchiolar epithelium, dysplastic maturation with cellular atypia, extensive epithelial erosion, and type II cell hyperplasia, all features of early BPD. The results of this study suggest that in the premature baboon model, exogenous surfactant therapy improves pulmonary functional abnormalities and lessens the histologic features of BPD, perhaps because of rapid weaning and reduced barotrauma. PMID- 2318052 TI - Relationship of bioimpedance to thermodilution and echocardiographic measurements of cardiac function. AB - Bioimpedance cardiography has been suggested as a noninvasive means to monitor cardiac function. However, this method has not been compared to more conventional techniques such as echocardiography. This study compared simultaneously obtained thermodilution cardiac output and right ventricular ejection fraction (RVEF), and echocardiographic left ventricular fractional shortening (LVFS), to bioimpedance cardiac output and the maximum first derivative of the bioimpedance signal (dZ/dtmax) during positive inotropic stimulation and preload reduction. Eight pigs were instrumented with a rapid response thermistor (positioned in the pulmonary artery) and bioimpedance electrodes. Simultaneous thermodilution, echocardiographic, and bioimpedance measurements were performed at baseline and after 5, 10, and 15 min of isoproterenol infusion (0.5 microgram/kg.min). In six pigs, measurements were also performed after balloon occlusion of the inferior vena cava. A significant correlation was observed between LVFS and dZ/dtmax (r = .88, n = 35) over all time points. Thermodilution and bioimpedance cardiac output were in close agreement (r = .92, n = 35). However, bioimpedance overestimated cardiac output in the very low and high output states. The mean difference between thermodilution and bioimpedance cardiac outputs was -0.02 +/- 0.37 L/min. There was a positive relationship between RVEF and dZ/dtmax (r = .54, n = 35). In summary, bioimpedance was significantly correlated with thermodilution cardiac output over a wide hemodynamic range. The peak first derivative of the bioimpedance signal dZ/dtmax may provide a noninvasive index of ventricular pump performance. Further studies are required to evaluate the diagnostic value of bioimpedance cardiography in the clinical setting. PMID- 2318053 TI - Local cerebral glucose utilization in septic rats. AB - To identify cortical and subcortical structures in the brain which are associated with septic encephalopathy, local cerebral glucose utilization (LCGU) in the 31 discrete regions were evaluated with a quantitative (14C)-2.deoxyglucose autoradiographic method in the septic rat model. Sepsis was produced by cecal ligation and punctures. Forty rats were subjected to behavioral study and divided into two groups (control, n = 15; sepsis, n = 25). Septic rats died within 36 h, and the rats developed behavioral depression, and showed EEG slowing and an increase in pain threshold. The latter was evaluated by a tail flick method within 8 h after the surgical procedures, while control rats did not show significant change in either behaviors or pain threshold. In another study, LCGU was measured when behavioral depression, increase in pain threshold, and EEG slowing developed in the sepsis group (n = 7). In this group, the mean LCGU in auditory and parietal cortices, lateral geniculate, superior colliculus, hippocampus, and locus ceruleus was 95, 74, 67, 69, 72, and 53 mumol.100 g-1.min 1, being lower by 23%, 22%, 18%, 19%, 14%, and 27% than that in the sham-operated control group (n = 7), respectively. However, the mean LCGU in septal and raphe nuclei was 52 and 84 mumol.100 g-1.min-1, being significantly higher by 27% and 33% than that in the control group, respectively. These results suggest that septic encephalopathy is associated with metabolic changes in the discrete brain regions, which are related to the serotonergic or noradrenergic system. PMID- 2318054 TI - Thermodilution cardiac output values obtained by using a centrally placed introducer sheath and right atrial port of a pulmonary artery catheter. AB - Thermodilution cardiac output measurements obtained using a centrally placed introducer sheath were compared with thermodilution cardiac outputs obtained using the right atrial port of a balloon-tip, flow-directed pulmonary artery catheter in 15 patients with cardiac failure. Cardiac output values were obtained by manually injecting 10 ml of iced, D5W alternately through the introducer sheath and the right atrial port of the flow-directed catheter. Thirty cardiac output readings were obtained in the 15 patients. Cardiac outputs obtained using the right atrial port (CORA) did not differ significantly from cardiac outputs obtained using the introducer sheath (COSP) (5.3 +/- 0.2 vs. 5.2 +/- 0.2 L/min). The correlation between CORA and COSP was significant (r = .94, p less than .0001) and could be described by the formula CORA = 0.33 + 0.96 COSP. We conclude that when the right atrial port of a flow-directed catheter is nonfunctional, a thermodilution cardiac output obtained using a centrally placed introducer sheath offers a reliable alternative. PMID- 2318055 TI - Serum prolactin concentrations in patients with the acquired immunodeficiency syndrome. AB - Experimental evidence suggests that prolactin is an important immunomodulator hormone. Because this endocrine-immune link may represent a potential new therapeutic avenue, we considered its application in states of immunodeficiency. We hypothesized that serum prolactin concentrations might be abnormal in AIDS. To test this hypothesis, we measured serum prolactin concentrations in blood samples obtained from patients who had either AIDS (n = 15) or AIDS-related complex (n = 12), asymptomatic subjects who were antibody-positive for human immunodeficiency virus (HIV) (n = 10), HIV antibody-negative homosexual subjects (n = 10), and heterosexual HIV antibody-negative controls (n = 21). We found no difference in the serum prolactin concentrations between the five subject groups. We conclude that circulating prolactin values are not altered by HIV infection; however, the possibility that prolactin administration may modulate immune function remains to be tested. PMID- 2318056 TI - Effects of acute illness on selenium homeostasis. AB - Biochemical evidence of selenium (Se) deficiency is frequent in patients with chronic malnutrition. However, the incidence of Se deficiency in acutely ill patients is unknown. In 175 consecutive ICU patients, plasma Se measured during the first week of ICU admission was 0.66 +/- 0.21 mumol/L (mean +/- SD) and was less than that measured in 57 healthy blood donors (1.05 +/- 0.21 mumol/L, p less than .001). Sixty-eight percent of plasma Se concentrations fell below the lower limit of the reference range. Plasma Se decreased with the number of weeks in the ICU (r = .33, p less than .01) with values decreasing to 0.49 +/- 0.20 mumol/L during the fourth week. Urinary Se excretion measured in a subgroup of 20 patients was related to plasma Se concentration (r = .38, p less than .05), and inversely related to N balance (r = .50, p less than .01). We conclude that decreased plasma Se concentrations are common in ICU patients and that catabolic states are associated with increased Se losses. These losses are unlikely to account for the marked reductions in plasma Se concentrations, and the findings suggest there may be significant changes in the distribution of body Se during critical illness. PMID- 2318057 TI - Respiratory distress syndrome and tracheoesophageal fistula: management with high frequency ventilation. AB - An 1180-g infant with esophageal atresia and tracheoesophageal fistula developed life-threatening respiratory distress syndrome. Conventional mechanical ventilation resulted in gastric perforation and pneumoperitoneum. High-frequency ventilation stabilized the infant, permitting distal occlusion of the esophagus with a Silastic band. Fistula ligation was subsequently performed under more optimal physiologic conditions. PMID- 2318058 TI - Legionella infection mimicking herpes encephalitis. PMID- 2318059 TI - Pulmonary artery versus pulmonary angiography catheters. PMID- 2318060 TI - Avoiding unintentional arterial cannulation. PMID- 2318061 TI - Transcardiac method of jugular bulb catheter placement. PMID- 2318062 TI - Importance of head-down posture in resuscitation. PMID- 2318063 TI - Acute benzodiazepine withdrawal after midazolam in children. PMID- 2318065 TI - Harris-Benedict approximation. PMID- 2318064 TI - Reliability of central venous pressure measured by water column. PMID- 2318066 TI - [The "second opinion". Experiences in the USA]. PMID- 2318067 TI - [The "second opinion": a workshop of the Professional Society of German Surgeons, 17 November 1989, in Hamburg. Legal medical aspects of section 137 paragraph 5 of the Federal Penal Code V]. PMID- 2318068 TI - [The "second opinion": a workshop of the Professional Society of German Surgeons, 17 November 1989, in Hamburg]. PMID- 2318069 TI - [Clinical use of new organ-saving technics in splenic surgery]. AB - During a period of 19 months, 22 organ preserving splenic operations were performed. Eleven of these, were severe third degree traumatic bursting ruptures, which were treated using a resorbable compressive mesh. An intralienal pancreatic cyst, a case of splenomegaly suspicious for lymphoma, one traumatic and two accidental polar lesions were treated by partial splenic resection using stapler. In two patients with traumatic and four with accidental first and second degree lienal lesions, collagen tampon and fibrin adhesive were employed. None of these patients required a second laparotomy. Aside from an edematous tail pancreatitis, no complications arose. Two patients succumbed to their severe cranial injuries. In the same period, four posttraumatic splenectomies were performed. Thus, excluding incidental and technical splenectomies, the application of the described methods resulted in orthotopic splenic preservation in 78% of traumatic splenic ruptures. PMID- 2318070 TI - [Blood loss and the need for homologous blood transfusion in elective general surgery as a basis for indications for preoperative autologous blood donation]. AB - The records of 279 surgical patients of 1986 were retrospectively evaluated for blood loss and blood-transfusion in order to provide a basis for an autologous blood donation program. 90% of the large bowel resections, gastrectomy and peripheral artery interventions with a blood loss between 0.5 and 1.51 could have been performed with the sole use of autologous blood. 50% of the operations of the abdominal aorta and all operations of the oesophagus would have required the additional use of other autotransfusion techniques or homologous blood transfusions. PMID- 2318071 TI - [Perioperative anemia and erythropoiesis]. AB - 50 consecutive patients with hip arthroplasty had acute normovolaemic haemodilution and intra- and postoperative autotransfusion using Autotrans, Dideco GmbH. 18 of 50 patients received homologous blood products additionally to autotransfusion (Hb less than 8 g/dl, hemodynamic instability). There was no evidence for coagulation disorders, hypoxia or hypovolaemia during the whole investigation period (until the 10th p.o. day) though in some cases haemoglobin levels less than 7 g% were accepted. No variations of erythropoietin levels could be observed postoperatively, suggesting that acute anaemia alone does not affect erythropoiesis. Reticulocytes, however, increased significantly from the 4th postoperative day. There was no correlation between number of reticulocytes and erythropoietin levels. Lactate levels stayed within normal range during the whole investigation period thus indicating normal microcirculation. The present data demonstrate that postoperative anaemia can be tolerated even in elder patients if intravascular volume is kept constant (normovolaemia). In accordance with recent literature the course of erythropoietin levels seemed to prove that there was no functional reduction in oxygen-availability. PMID- 2318072 TI - [A technic of peranal anastomosis]. PMID- 2318073 TI - [Malignant hemangioendothelioma of the spleen as an incidental finding of abdominal surgery]. PMID- 2318074 TI - [Bronchobiliary fistula]. PMID- 2318075 TI - [Ruptured renal angiomyolipoma as a cause of acute abdomen]. PMID- 2318076 TI - [A simple method for measuring anal sphincter pressure]. PMID- 2318077 TI - [Reuse of disposable equipment from the legal viewpoint]. PMID- 2318078 TI - [Initial management of severe injuries of the head and trunk from the viewpoint of plastic surgery]. PMID- 2318080 TI - Molecular control of haemopoiesis. PMID- 2318079 TI - [Use of plastic surgery methods in primary management of limb injuries]. PMID- 2318081 TI - Multiparametric analysis of cell membrane permeability by two colour flow cytometry with complementary fluorescent probes. AB - We describe an improved twin-probe multiparameter flow cytometric technique to examine cell membrane permeability. Ability to retain preloaded intracellular bis carboxyethyl carboxy fluorescein (BCECF, green fluorescence) and to exclude extracellular propidium (red fluorescence) is measured, simultaneously with forward and right-angle scatter. This has significant advantages over an earlier method using fluorescein together with ethidium. In addition to the two expected cell populations which were stained green positive, red negative (by convention membrane "intact" and "viable," Region 1) and green negative, red positive ("membrane-damaged" and "non-viable," Region 3), a third population was seen which fluoresced neither green nor red and displayed intermediate light scatter characteristics (Region 2). This was true for each of 9 cell types in vitro. For EMT6 mouse mammary tumour cells held under sub-optimal conditions or treated with membrane-active drugs, progression from Region 1 to Region 2 was observed, followed by further progression from Region 2 to Region 3. Cells eventually accumulated in Region 3. These results suggest that sequential changes in membrane structure lead to increased permeability, first with respect to intracellular BCECF and in turn to extracellular propidium. PMID- 2318083 TI - Flow cytometric detection of multifocal DNA aneuploid cell populations in mastectomy specimens containing a primary breast carcinoma. AB - DNA flow cytometry was used to study the presence of DNA aneuploid cell populations in macroscopically normal glandular tissue in mastectomy specimens from 30 patients with breast cancer. In the 13 patients with a DNA diploid primary tumor, no DNA aneuploidy could be found in any of the 39 distant specimens assessed. However, DNA aneuploid cell populations were demonstrated in four of the 17 (23%) patients with a primary DNA aneuploid carcinoma and in seven out of 54 (13%) distant tissue samples (P = 0.02). In all cases the DNA index of the DNA aneuploid cells found in the distant samples was identical to that of the primary tumor. The replicate aneuploid DNA indices and histologic controls taken in parallel very strongly suggest that these distant DNA aneuploid cell populations are metastases. PMID- 2318082 TI - Changes in neutrophil right-angle light scatter can occur independently of alterations in cytoskeletal actin. AB - Forward-angle light scatter (FALS) and right-angle light scatter (RALS) are commonly employed to discriminate between leukocyte subclasses. Recently the application of RALS has expanded, and it is now also used as an indicator of neutrophil actin polymerization. In this communication we critically examine the relationship of RALS to changes in cytoskeletal actin. The data indicate that agonists which stimulate an increase, a decrease, or no change in F-actin content can all stimulate a biphasic change in RALS. We therefore conclude that changes in RALS can occur independently of changes in F-actin content. This leads us to suggest that caution must be taken when interpreting RALS data in relation to changes in F-actin. Furthermore, the data also support the idea originally proposed by Yuli and Snyderman (J Clin Invest 73:1408-1417, 1984), that RALS may be an exceptionally sensitive indicator of cell activation. PMID- 2318084 TI - Interfacing a flow cytometer computer with a PC-based patient information system. AB - We have established an interface between our flow cytometer's computer and the personal computer (PC) which supports our patient database system. The PC has been equipped with a commercially available IEEE-488 bus interface board which is connected to the interface bus of the cytometer's Hewlett-Packard 9000/300 computer (HP). The PC is set as a bus device with the same address as that of the HP's printer. It is programmed to examine the stream of data sent to the printer and extract from it and store in an MS-DOS text file selected information which subsequently may be transferred to the database system. PMID- 2318085 TI - Improved method for computing potential doubling time from flow cytometric data. AB - Relative movement methods use the timed progression of the mean fluorescence of cells which have been labeled with monoclonal antibodies against bromodeoxyuridine and displayed with bivariate flow cytometry according to DNA and label content to compute duration of DNA synthesis, TS. The relative movement is the difference of the mean DNA fluorescence of the labeled undivided cells from the G1 channel relative to the difference between the G1 and G2M channels. In this communication, we show how to extend this method to compute the potential doubling time, Tpot, the time required for a population of cells to double, given quiescent cells but no cell loss. A quantity v is introduced that is a function of the fraction of labeled divided cells and the fraction of labeled undivided cells. We show that v is independent of time and is equal to ln(2)Ts/Tpot so that Tpot (equal to ln(2)Ts/v) can be directly found from the information available in computing the relative movement. The method is applied to Chinese hamster ovary cells to demonstrate its utility. PMID- 2318086 TI - Characteristic immunophenotyping artefact seen in patients with anti-mouse immunoglobulin antibodies. AB - Patients treated with murine monoclonal antibodies develop anti-mouse immunoglobulin antibodies which can interfere with flow cytometry of lymphocytes, giving rise to high levels of nonspecific staining. This artefact can be avoided by using separated, washed lymphocytes for immunophenotyping. PMID- 2318087 TI - Exercise increases solid meal gastric emptying rates in men. AB - Gastric emptying rates of radiolabeled beef stew meals were measured in 10 healthy, young (median age = 27 years) male subjects on each of three randomly chosen study days. The subjects either (1) stood at rest, (2) walked on an exercise treadmill at 3.2 km/hr, or (3) at 6.4 km/hr during the study while gastric emptying was being monitored by externally positioned gamma cameras. Compared to the standing at rest study, exercise significantly increased gastric emptying (at rest emptying half-time (t1/2) = 72.6 +/- 7.6 (SEM) min; 3.2 km/hr t1/2 = 44.5 +/- 3.9 min, P = 0.0051; 6.4 km/hr t1/2 = 32.9 +/- 1.9 min, P = 0.0051). The 6.4 km/hr emptying time was significantly (P = 0.0249) faster than the 3.2 km/hr emptying time. Thus, the amount of exercise is a physiological factor that alters solid meal gastric emptying rates. PMID- 2318088 TI - Impact of diet and smoking on risk of developing intestinal metaplasia of the stomach. AB - A cohort of Hawaii Japanese men was assembled for epidemiologic studies of heart disease and cancer. Diet and tobacco consumption data were obtained from 1965 to 1968 and from 1971 to 1975. Biopsies from sites at maximal, intermediate, and minimal risk of intestinal metaplasia were performed on 350 men. Metaplasia was found in 234 men. Gastric cancer was found in 9/234 with metaplasia (3.8%) and 1/116 men without metaplasia (0.89%). Nitrite-rich salty foods (e.g., cured meats) were directly related to metaplasia at both examinations. Vitamin C intake did not appear to have prevented the development of intestinal metaplasia. Smoking was directly related to the presence of metaplasia, but the association was weaker than was observed for cured meats. The strong association between nitrite-rich salty foods and metaplasia appears to be uniform from one study to another, as is the lack of a consistent relation between metaplasia and either smoking or vitamin C consumption. Heavy smokers were more likely to have metaplasia than were nonsmokers, but these associations were weaker than were those with cured meats. PMID- 2318089 TI - Inhibitory effect of neurotensin on gastric acid secretion in rats. Development of a bioassay model. AB - Neurotensin has been shown to inhibit gastric acid secretion when administered in pharmacological doses, but no information has been available concerning its possible dose-related effect during intravenous infusion. In this study, a dose related and reversible inhibitory effect of neurotensin was demonstrated in pentobarbital-anesthetized female Sprague-Dawley rats. The rats underwent continuous gastric perfusion with saline, 1 ml/min, and intravenous infusion of both pentagastrin and neurotensin. Inhibition of acid secretion did not depend upon the occurrence of hypotension, and ranged from 35 +/- 7% of maximal acid output at 0.24 nmol/kg/hr to 60 +/- 10% at 7.2 nmol/kg/hr of neurotensin. Blood levels of C-terminal neurotensin-like immunoreactivity were proportional to the dose of peptide infused and were 52 fmol/ml during infusion of 0.24 nmol/kg/hr, a dose that significantly inhibited pentagastrin-induced acid secretion. Thus, a model has been developed to study the effect of neurotensin infusion on acid secretion; the concentration of plasma neurotensin-like immunoreactivity at which inhibition occurs in this model is similar to the concentration reported to occur after a nutrient stimulus. PMID- 2318090 TI - The effect of acute and chronic ethanol administration on gastric emptying in cats. AB - There continues to be disagreement regarding the effects of ethanol on gastric emptying. This study was designed to assess different degrees of ethanol exposure on gastric emptying. Scintigraphic gastric emptying studies were performed in healthy adult cats and the half time (t1/2) of gastric emptying was obtained from each study. Repeat measures of gastric emptying were again obtained in these cats under the conditions of both acute and chronic ethanol exposure and 24 hr following ethanol withdrawal. Gastric emptying half times were prolonged significantly during acute and chronic exposure to ethanol. The mean value for t1/2 under control conditions was 46.46 min, while for acute and chronic exposure to ethanol the mean t1/2 values were 69.34 and 91.33 min, respectively. In addition, we demonstrated a similar delay in gastric emptying during active withdrawal from alcohol (t1/2 = 70). We conclude that both acute and chronic alcohol exposure significantly delay gastric emptying. PMID- 2318091 TI - Canine gastric muscarinic receptors up-regulate after vagotomy. AB - Postvagotomy (PV) gastroparesis is an infrequent but troublesome problem. To test the hypothesis that the rarity of the PV syndrome is due to compensatory up regulation of muscarinic cholinergic receptors (mAChR), we measured changes in stomach mAChR and gastric acid secretion in dogs before and three weeks after truncal vagotomy. Maximum acid output dropped significantly one week PV and then partially recovered by three weeks PV. mAChR density changed in parallel and was significantly increased in body mucosa, body muscle, and antrum mucosa. In the body, changes in mAChR in mucosa correlated positively with changes in muscle, suggesting that mAChR binding in pinch biopsies of gastric mucosa might become useful in evaluating patients for postvagotomy syndrome. PV up-regulation of mAChR in the mucosa of the canine gastric body might explain PV recovery of gastric acid secretion. PMID- 2318092 TI - Body temperature-dependent action of baclofen in rat stomach. Relation to acid secretion and ulcerogenicity. AB - The effect of baclofen (PCPGABA) on acid secretion, motility, and mucosa was investigated in the anesthetized rat stomach under various body temperatures (BT: 28-38 degrees C), and they were compared with those of 2-deoxy-D-glucose (2DG), an acid stimulant through cytoglycopenia. Under these conditions PCPGABA induces lesions dose-dependently (greater than 1 mg/kg, subcutaneously) in both the stomach and duodenum, and this action was dependent on BT; lowering of BT enhanced the ulcerogenicity. PCPGABA (3 mg/kg) had no effect on acid secretion at higher BT (36-38 degrees C) but produced a marked increase of acid output at lower BT (30-32 degrees C). 2DG caused a stimulation of acid output and gastric lesions without BT dependency, but the duodenal ulcerogenicity enhanced at lower BT. Gastric motility was enhanced significantly by these two agents to similar degrees, at either high or low BT. Neither PCPGABA nor 2DG affected alkaline secretion in the duodenum, while lowering of BT by itself reduced alkaline secretory responses. The above changes caused by PCPGABA and 2DG were blocked by both atropine and vagotomy. These results suggest that (1) acid stimulatory and ulcerogenic action of PCPGABA may involve a temperature-dependent process but does not relate to a cytoglycopenia, and (2) the vagus nerve mediating acid secretion and motility may be different in the temperature dependency. PMID- 2318094 TI - Contributions of evacuation proctography and anorectal manometry to evaluation of adults with constipation and defecatory difficulty. AB - We prospectively evaluated 36 patients who complained of chronic constipation and/or defecatory difficulties to determine the role of anorectal manometry and evacuation proctography in delineating the pathogenesis of these complaints. Twenty patients with constipation also underwent a colonic transit study with radioopaque markers, which identified one group with normal transit (N = 10) and another with slow transit (N = 10). Nine of 36 patients (25%) had inappropriate puborectalis muscle contraction or exhibited weak expulsion efforts during evacuation proctography, and these correlated highly with poor rectal emptying of barium paste (20 +/- 6% vs 61 +/- 5% in patients with normal relaxation; P less than 0.01). However, poor rectal emptying did not correlate with the presence of high-grade intussusceptions, large rectoceles, anorectal angles at rest or with straining, rectal diameter, clinical features, or colonic transit. Moreover, abnormal expulsion patterns as seen with anorectal manometry correlated poorly with the presence of inappropriate puborectalis contraction and decreased rectal emptying by proctography. Although anatomic abnormalities occurred frequently in patients with constipation and/or defecatory difficulties, they were also prevalent in asymptomatic controls. In view of these findings, surgical intervention to correct anatomic abnormalities in patients with constipation and/or defecatory difficulties should be considered only with great caution. PMID- 2318093 TI - Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture. AB - The present study evaluated the effect of sucralfate and its components, sucrose octasulfate and aluminum hydroxide, on: (1) damage to rat cultured gastric mucosal cells induced by sodium taurocholate in a neutral environment and in conditions independent of systemic factors, (2) prostaglandin E2 and on 6-keto prostaglandin F1 alpha release by cultured cells, and (3) sulfhydryl content of cultured cells. Cell damage was quantitated by chromium-51 release assay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were measured by radioimmunoassay. Total sulfhydryl content of cultured cells was determined calorimetrically. Microscopically, sucralfate was found to adhere tightly to epithelial cell surfaces despite frequent washings. Sucralfate 2 mg/ml and 5 mg/ml significantly decreased taurocholate-induced damage, reducing taurocholate induced specific 51Cr release by 11.8 points (equal to 29% decrease in cell damage, P less than 0.01) and 22.9 points (equal to 56% decrease in cell damage, P less than 0.001), respectively. Sucrose octasulfate and aluminum hydroxide did not exert significant protection against damage induced by sodium taurocholate. The protective effect of sucralfate was not prevented by indomethacin, nor was it counteracted by the sulfhydryl blocker, iodoacetamide. Sucralfate, but not its components, significantly and dose-dependently stimulated prostaglandin E2 (r = 0.94, P less than 0.05) and 6-keto prostaglandin F1 alpha (r = 0.89, P less than 0.05) production by cultured cells. Neither sucralfate nor its components affected sulfhydryl content of cultured cells. In conclusion, sucralfate, but not its components, (1) protects rat gastric mucosal cells against taurocholate induced damage in conditions independent of systemic factors and in a neutral environment and (2) significantly stimulates prostaglandin production by cultured cells. (3) The protection by sucralfate in vitro does not seem to depend on its stimulatory effect on endogenous prostaglandin synthesis. PMID- 2318095 TI - Restoration of colorectal continuity reverses atrophy in human rectal mucosa. AB - Cell kinetic activity and adaptive response of rectal mucosa from patients with Hartmann's procedure were studied before and after restoration of colorectal continuity. Patients without colostomy and with normal rectal mucosa were used as controls. Autoradiography of in vitro labeled mucosal samples with [3H]thymidine was used. The proliferative activity in the rectal crypts was estimated by measuring labeling and mitotic indices, total DNA of isolated crypts, and total crypt cell numbers. One hundred forty days after creating a proximal end colostomy, labeling index (P less than 0.05), mitotic index (P less than 0.01), DNA content per crypt (P less than 0.05), and number of cells per crypt (P less than 0.05) decreased significantly compared to control values. Restoration of colorectal continuity resulted in a significant increase of the labeling index (P less than 0.05), the mitotic index (P less than 0.01), the DNA content per crypt (P less than 0.05), and the cell number per crypt (P less than 0.05). There were no significant differences between the postclosure values and the controls. These data indicated that excluding the human rectal mucosa from fecal stream determined a mucosal atrophy that could be reversed by restoration of colorectal continuity. PMID- 2318096 TI - Long-duration stress. Immediate and late effects on small and large bowel motility in rat. AB - No extensive information exists in literature concerning the late or residual effects of stress on motility of small bowel and colon. Moreover, the duration and magnitude of the intestinal motor response to stress are still ignored. Therefore, the aim of our work was to determine, in rat, the effect of long duration stress induced by restraint on the motility of small bowel and colon. Observations were made during physical restraint and 60 h later. Bipolar electrodes were implanted on the gastrointestinal serosa from the pylorus to the sigmoid colon in male Wistar rats. Electromyographic (EMG) recordings were made during fasting state, and a control EMG recording session was performed during 12 hr, followed by a 12-hr recording during restraint stress. After a 60-hr resting period, another EMG recording session was performed during 3 hr. During stress in the pylorus and small bowel, the recurrence of migrating myoelectrical complexes (MMCs) was immediately interrupted and replaced by a continuous and irregular activity. The motility index (number of spike bursts/10 min) was augmented rapidly on the jejunum and ileum, but it increased only gradually on the pylorus. Only on the transverse colon were the number of spike bursts/hour and their relative duration increased after 7 hr of physical restraint. In contrast, the sigmoid colon displayed a gradual decrease in the relative duration of contractile activity during the first 6-7 hr of stress. At 60 hr after stress in the pylorus and small bowel, a normal control motor activity was restored (MMC, motility index) on the jejunum and on the ileum, but the motility index on the pylorus was decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318097 TI - Endorectal cerebral evoked potentials. PMID- 2318098 TI - Gastric analysis (basal acid output) in nonulcer dyspepsia. PMID- 2318099 TI - Psychological characteristics of adults with IDDM. Comparison of patients in poor and good glycemic control. AB - This study was conducted to evaluate selected psychosocial characteristics of contrasting groups of patients with insulin-dependent diabetes mellitus (IDDM), i.e., patients with persistently poor versus good glycemic control. Patients with chronic poor control reported feeling physically best at higher blood glucose levels than patients with good control. They also reported a higher threshold for physical symptoms caused by hyperglycemia without any difference in threshold for hypoglycemic symptoms. No differences between groups were found in level of diabetes knowledge, self-esteem, or psychiatric symptomatology. This study suggests that poorly controlled adult patients have underlying perceptions of hyperglycemic symptoms and physical well-being that distinguish them from patients with well-controlled diabetes. The design of this study does not allow for determination of the causal direction in this relationship. Although these patient reports about glycemic and physical symptoms may be post hoc justifications or unreliable beliefs, they also may be accurate perceptions of physical symptom experiences and therefore could influence their self-care activities with resulting chronic problems in glycemic control. Further research is needed to assess the validity of these observations and their possible role in long-term regulation of glycemia. PMID- 2318100 TI - Development of questionnaire to examine relationship of physical activity and diabetes in Pima Indians. AB - There was a need to design a questionnaire that could accurately assess the activity patterns of Native Americans to evaluate the relationship between physical activity and diabetes. Such a questionnaire was developed and implemented into the data collection scheme of the prospective Pima Indian Study of Arizona. The questionnaire, which assesses historical, past-year, and past week leisure and occupational activity, was examined in 29 Pima individuals aged 21-36 yr and was shown to be reliable with test-retest correlations (rank-order correlations ranged from 0.62 to 0.96 for leisure and occupational activity). Reproducibility of the past-year leisure physical-activity estimate was determined in 69 participants aged 10-59 yr and was found to be reliable in all age-groups with the exception of the 10- to 14-yr-old age-group (rank-order correlations were 0.31 in the 10- to 14-yr-old age-group compared to 0.88 to 0.92 in those greater than 20 yr of age). Validity of the current-activity section of the questionnaire was demonstrated indirectly through comparisons with activity monitors. The past-week leisure-activity estimate was related to the Caltrac activity monitor counts per hour (rho = 0.62, P less than 0.05, n = 17). In summary, a physical-activity questionnaire has been developed that is both reliable and feasible to use in the Pima Indian population to evaluate the relationship of physical activity to non-insulin-dependent diabetes mellitus. PMID- 2318101 TI - Evidence for early impairment of macular function with pattern ERG in type I diabetic patients. AB - The electroretinogram (ERG) elicited by alternating gratings at constant mean luminance (pattern ERG) is a focal response reflecting the activity of the directly stimulated retinal area. In addition, pattern ERG is related, unlike the flash ERG, to ganglion cell activity. Therefore, this technique may be used to evaluate the integrity of inner retinal layers in the macular region. In this study, the steady-state pattern ERG, in response to alternating gratings (1.7 cycles/deg spatial frequency; 9 degrees field size) temporally modulated at 8 Hz, was recorded in 42 type I (insulin-dependent) diabetic patients with zero to four microaneurysms on fluorescein angiography and a duration of disease less than 11 yr. No patient had concomitant ocular or systemic complications. Mean pattern-ERG amplitude was significantly reduced in patients compared with age-matched control subjects (analysis of variance, F = 25.6, P less than 0.0001). Significant differences were observed between control and diabetic subjects without retinopathy (Scheffe F test, P less than 0.0001), between control and retinopathic subjects (Scheffe F test, P less than 0.0001), and between diabetic patients without retinopathy and those with early retinopathy (Scheffe F test, P less than 0.02). Pattern-ERG amplitude was inversely correlated with duration of diabetes (r = 0.22, P less than 0.05). Our results suggest a macular dysfunction in early diabetes resulting from metabolic and/or vascular injuries in the neurosensory retina. PMID- 2318102 TI - Testing for blood glucose by office-based physicians in the U.S. AB - A national sample of 2879 physicians were surveyed to ascertain characteristics of patient visits for diabetes including whether any test had been ordered or provided or a specimen taken to assess the patient's blood glucose level. Based on survey data, an estimated 21.3 million visits were made for diabetes in 1985. Of these, 16.8 million were for continuing care of diabetes by primary-care physicians, an average of 2.7 visits/yr for the 6.1 million U.S. residents diagnosed as having diabetes. A test for blood glucose was associated with 69% of these visits, an average of 1.9 times/yr per patient with diabetes in the U.S. Rates of testing for blood glucose varied by source of payment for the visit and were higher when diabetes was the primary diagnosis and when the number of physicians practicing together was greater, such as in health maintenance organizations or group practices. Rates of testing did not differ by age, race, or sex of the patient; location of the physician's practice; whether insulin or oral agents were prescribed; or a number of other characteristics. Other studies indicate that self-monitoring of blood glucose is performed by less than 10% of diabetic patients. Hence, the physician's office remains an important location for assessment of diabetes control by measurement of blood glucose levels. PMID- 2318103 TI - Cigarette smoking and neuropathy in diabetic patients. AB - We studied whether lifetime cigarette smoking is associated with the presence of diabetic neuropathy. The research design consisted of a case-control study conducted from a referral-based diabetes clinic at a major medical center. The patients were a 65% sample (163 insulin-dependent diabetes mellitus [IDDM] and 166 non-insulin-dependent diabetes mellitus [NIDDM] patients) of all patients admitted during a 26-mo period. Neuropathy was diagnosed on the basis of signs and symptoms. Smoking history was obtained by mailed questionnaire (66% response rate). Diabetes duration, HbA1, age, sex, peripheral vascular disease, hypertension history, and lifetime alcohol consumption were measured as covariates. The prevalence of neuropathy was 49 and 38% in IDDM (n = 113) and NIDDM (n = 104) patients, respectively. In IDDM, but not NIDDM, current or ex smokers were significantly more likely to have neuropathy than individuals who had never smoked (odds ratio 2.46, P = 0.02), and the prevalence of neuropathy increased with increasing number of pack-years smoked (P less than 0.001). After adjustment for covariates, IDDM patients smoking greater than or equal to 30 pack yr were 3.32 times more likely to have neuropathy than patients smoking less than this amount (95% confidence interval 1.15-9.58, P = 0.026). Cigarette smoking was associated with the presence of neuropathy in this clinic-based population of IDDM patients. The hypothesis that cigarette smoking is associated with diabetic neuropathy should be investigated further, both prospectively and in a more representative population. PMID- 2318104 TI - Arterial blood pressure related to degree of albuminuria and low-molecular-weight proteinuria in IDDM. AB - Urinary excretion of albumin and retinol-binding protein (a marker of tubular proteinuria that results from impaired proximal tubular reabsorption of low molecular-weight proteins) was determined in 110 insulin-dependent diabetic (IDDM) subjects. A statistically significant correlation between the urinary excretion of both proteins, in particular the retinol-binding protein, and the height of arterial blood pressure (systolic and diastolic) was observed. Correlation was weak, i.e., factors other than incipient nephropathy could be of greater importance for the development of arterial hypertension in diabetes. PMID- 2318106 TI - Targeting professional education. Pragmatism, priorities, and patience. PMID- 2318105 TI - Effects of changing amount of carbohydrate in diet on plasma lipoproteins and apolipoproteins in type II diabetic patients. AB - Eight type II (non-insulin-dependent) normolipidemic diabetic patients (aged 45 +/- 15 yr, body mass index 22 +/- 2 kg/m2, means +/- SD) treated with diet alone or diet plus oral hypoglycemic agents were given, in random order for periods of 15 days, two diets with different carbohydrate (CHO) (40 vs. 60% of total calories) and fat (20 vs. 40%) levels. Simple CHO, fiber, saturated fat, cholesterol, and polyunsaturated-saturated fat ratio were similar in the two diets. Total plasma cholesterol was not significantly affected by dietary changes; conversely, plasma triglyceride (1.38 +/- 0.59 vs. 1.11 +/- 0.39 mM, P less than 0.05) and apolipoprotein CII (3.8 +/- 1.4 vs. 3.3 +/- 0.8 mg/dl) increased significantly after the high-CHO low-fat diet. Among the various lipoproteins, very-low-density lipoprotein (VLDL) was the most affected by diet: VLDL cholesterol concentrations increased from 0.30 +/- 0.19 to 0.43 +/- 0.28 mM (P less than 0.05), and triglyceride concentrations increased from 0.62 +/- 0.33 to 0.88 +/- 0.53 mM (P less than 0.05). In conclusion, increasing the amount of complex CHO in the diet induces an elevation of VLDL in normolipidemic, nonobese, mildly type II diabetic patients. PMID- 2318107 TI - Systolic hypertension in IDDM patients with hyperfiltration and normal albumin excretion rates. PMID- 2318108 TI - SMBG in NIDDM patients treated by general practitioners in France. PMID- 2318109 TI - ExacTech cheating. PMID- 2318110 TI - Acute hypoglycemic effect of Opuntia streptacantha Lemaire in NIDDM. PMID- 2318111 TI - Adjustment to diabetes mellitus in preschoolers and their mothers. PMID- 2318112 TI - Psychobehavioral metabolic parameters of severe hypoglycemic episodes. PMID- 2318113 TI - [Infections following kidney transplantation under threefold or fourfold immunosuppressive treatment]. AB - To determine, whether the infection rate after renal transplantation is influenced by the intensity of immunosuppressive treatment, the postoperative course of 100 consecutive renal transplantations in 64 men and 36 women (mean age 44.1 [18-72] years) was investigated prospectively. 87 patients received threefold basal immunosuppression with low-dose ciclosporin, azathioprine and prednisolone. In 13 risk patients (retransplantation and [or] high panel-reactive antibody titres), poly- or monoclonal antibodies were administered additionally to prevent rejection. Steroid-resistant rejection crises had to be treated with poly- or monoclonal antibodies in 15 patients. Postoperatively there were 10 patients with systemic infections (5 with cytomegalovirus, 4 with herpes simplex virus and 1 with Pneumocystis carinii). The infection rate with three- or fourfold immunosuppression did not differ significantly (5.4% vs. 9.1%). However, infections occurred more frequently after additional antirejection treatment with poly- or monoclonal antibodies (33%). It is concluded from these results that fourfold basal immunosuppression treatment with poly- or monoclonal antibodies is not associated with an increased risk of perioperative infections. PMID- 2318114 TI - [The early recurrence of Crohn's disease after "curative" ileocecal resection. A prospective endoscopic and histological study]. AB - The postoperative course of 44 patients (24 women, 20 men; mean age 31.5 [18-63] years) treated by ileocaecal resection for Crohn's disease was investigated prospectively. None of the patients received any prophylactic drug treatment during the 12-month postoperative period of observation. Recurrence of Crohn's disease was endoscopically diagnosed in 21 of the 44 patients during the 12-month period, and in 14 patients recurrence was suspected. Histological confirmation of recurrent Crohn's disease, however, was obtained unequivocally in only 11 patients, while in further 20 patients there was suspicion of recurrence. A large proportion of the recurrences was already confirmed endoscopically and histologically by the end of the third postoperative month. It is concluded that recurrences are frequent and early after a "curative" operation, raising the question of early prophylaxis with drugs. PMID- 2318115 TI - [Pampiniform livedo--an acute cardinal symptom of a cutaneous cholesterol embolism]. AB - Acute, painful, persisting, pampiniform and asymmetrical skin discolorations over the legs occurred after retrograde femoral artery catheterization in three patients suspected of having renal artery stenosis. The cause was found histologically to be embolization of cholesterol crystals to the arterioles of the corium-subcutis. Under treatment with acetylsalicylic acid the painful cutaneous changes gradually regressed. The possibility of cholesterol crystal emboli from atheromatous plaques in the aorta should be considered if the described skin changes occur, especially in the legs and with normal arterial pulsations. Proof lies in the histological picture of slit-like spaces in the arteriolar vessels at the corium-subcutis juncture, previously occupied by cholesterol crystals dissolved during fixation, and surrounding inflammatory changes with vessel wall thickening. PMID- 2318116 TI - [Fulminant venous and arterial thromboses under heparin therapy]. AB - A deep-vein thrombosis developed in a 71-year-old patient on the eleventh day of heparin treatment (25,000 U intravenously over 24 hours) given because of a nontransmural anterior-wall infarct. Subsequently there occurred a unilateral and then bilateral thrombotic occlusion of the femoral arteries and thrombosis of the infrarenal artery with occlusion of the right renal artery which necessitated operative thrombectomy. Platelet count, initially 370,000/microliters, fell to 34,000/microliters. No source of emboli was found either echocardiographically or by thoracic and abdominal computed tomography. After heparin administration had been discontinued on the 15th day, platelet count quickly returned to normal. Rapidly progressing demarcation necessitated amputation of both legs. The patient died on the 23rd hospital day. The reported findings indicate a heparin-induced thrombosis-thrombocytopenia syndrome. PMID- 2318117 TI - [Aluminum hydroxide granuloma following hepatitis B vaccination]. PMID- 2318118 TI - [Type-IV renal tubular acidosis]. PMID- 2318119 TI - [Coffee and serum cholesterol]. PMID- 2318120 TI - [Coronary artery stenoses close to the ostia after mediastinal irradiation]. AB - A 42-year-old man who 16 years previously had had mediastinal radiotherapy (total focal dosage of 52 Gy) for a malignant lymphoma, developed chest pain on mild exertion. Coronary arteriography during a diagnostic cardiological work-up revealed a 50-70% stenosis of the right coronary artery near its origin and a 90% stenosis in the main left coronary artery. Except for being slightly over-weight (85 kg at a height of 181 cm) there were no risk factors for coronary heart disease and there was no evidence for arterial disease elsewhere. A double aortocoronary vein graft was placed to the right coronary artery and the interventricular branch of the left coronary artery. The postoperative course was unremarkable and the patient has resumed his occupation. This report emphasizes that, in case of atypical chest pain after mediastinal radiotherapy, coronary heart disease as a late complication should be considered. PMID- 2318121 TI - [Professional legal duty of cooperation for "senior contractors"?]. PMID- 2318122 TI - Psychosocial consequences of caesarean childbirth: a four-year follow-up study. AB - This paper describes the last part of a study on the long-term psychosocial consequences of caesarean delivery. One group of 103 primiparous caesarean delivered women and one control group of 103 women delivered vaginally were followed from delivery to the children's fourth birthday. Previous assessments were made at birth, two months and one year later (Garel, M., Lelong, N. and Kaminski, M. (1987) J. Psychosom. Obstet. Gynecol., 6, 197-209 and (1988) Early Hum. Dev., 16, 271-282). Four years after delivery, 58 mothers of the caesarean group and 50 mothers of the control group returned a completed questionnaire. The questionnaire included questions about subsequent pregnancies and mother's and child's general state of health. The comparisons between respondents and non respondents showed no significant difference with regard to social and medical factors. As far as possible, factors which might have interfered with the mothers' and children's conditions were controlled in the analysis. There was no association between the method of delivery and the mother's overall state of health. However, after a caesarean section, mothers tended to have fewer children and more difficulty in conceiving. Four years after delivery, mothers in the caesarean group reported fatigue more frequently than control mothers. Five mothers (9%) consulted a psychiatrist, none in the control group (P less than 0.09). Between one and four years, caesarean born children had more hospital admissions but their overall behaviour and development, as reported by the mothers, was not different from those of children in the control group. PMID- 2318124 TI - Abstracts of papers presented at the Neonatal Society Meeting. PMID- 2318123 TI - Breast-feeding in a Danish alternative birth center compared with the obstetrical ward. AB - In 1984 an Alternative Birth Clinic (ABC) was opened at the Copenhagen County Hospital in Glostrup. The ABC was opened on a trial basis to evaluate the demand for a different and more peaceful birth and nursing environment. The study was performed to illustrate how the place of birth can influence the delivery and the duration of breast-feeding. During the observation period of seven months there were 125 uncomplicated births at the ABC, and 170 uncomplicated births at the obstetrical ward. It was not possible to perform this study as a randomized one as delivering at the ABC was on offer to all women in this part of Copenhagen County. The newborn children at the ABC were nursed during the first 30 min after birth by 73.1% of the mothers compared to only 48.1% of the mothers at the obstetrical ward. On the fifth day after delivery 79.7% of the mothers at the ABC breast-fed without supplementary infant formula, while 95.1% of the mothers at the obstetrical ward breast-fed without supplement. Fourteen weeks after delivery 68.4% of the mothers who delivered at the ABC were breast-feeding without supplement, compared to 51.8% of the mothers who delivered at the obstetrical ward. The success of breast-feeding was found to have a positive correlation to higher social groups, delivering at the ABC, the number of antenatal care visits and increasing maternal age. The significance of these factors was tested in a regression analysis which revealed that birthplace and social group were the two factors that could explain the differences in the course of breast-feeding. Women referred to the obstetrical ward because there were no vacancies at the ABC (ABC refused) followed in all aspects the mothers at the obstetrical ward. In spite of the groups not being randomized we feel that we can conclude, especially taking into consideration the results from the ABC-refused group, that the differences in the success of breast-feeding can be explained by the place of birth, and that making the birthplace and the surroundings more inviting will be very profitable for the length of breast-feeding. If possible the staff should spend more time with the delivering women and later assist them in getting a good start of breast feeding. PMID- 2318125 TI - Maternal plasma zinc levels and first trimester abortion. PMID- 2318126 TI - Weight loss in full-term negroid infants: relationship to body water compartments at birth? AB - The possible influence of the body fluid compartments at birth on postnatal weight loss was studied in normal term negroid infants when on a standardized oral fluid, sodium and energy regimen during the first three days of life. Measurements of plasma volume (PV), total body water (TBW), and extracellular water (ECW) were performed simultaneously on vaginally-born infants on the first day of life, by using a triple indicator (Evans blue, deuterium oxide and sucrose) single injection dilution technique. PV was 54 +/- 7 ml/kg (N = 9), TBW was 751 +/- 50 ml/kg (N = 13) and ECW was 311 +/- 61 ml/kg (N = 13) (mean +/- S.D.). Postnatal weight loss (3.7% of birth weight) occurred during the first two days. The postnatal weight loss was not related to any of the body water compartments. However, there was a highly significant correlation with the (cumulative) urine water excretion (r = 0.833, P less than 0.001 on day 1, with similar values for days 1 and 2). PMID- 2318127 TI - Bronchopulmonary dysplasia and postnatal growth in extremely premature black infants. AB - Bronchopulmonary dysplasia (BPD) may adversely affect the postnatal growth of the extremely premature infant; however, most studies have not controlled for birth weight. We studied 90 Black premature infants (mean birth weight 989 +/- 148 g). Weight was recorded biweekly until discharge and at 4, 8, and 12 months of age corrected for prematurity. Infants with BPD (N = 23) were contrasted with infants without BPD (N = 67). Data were modeled using the Count model: Stage I birth to term and Stage II term to 12 months. Birth weight was considered part of growth beginning in utero and multivariate analyses were used to control for BPD, gestational age, duration of hospitalization and socioeconomic status. After adjustment for birth weight, BPD did not explain the growth pattern. A lower gestational age was associated with a slower establishment of steady growth (P less than 0.01), while an increased duration of hospitalization was associated with a lower growth rate (P less than 0.05). Growth in stage II was not explained by study variables. 'Catch-up' growth was seen in both infants with and without BPD. We conclude that differences in growth among infants with BPD are mainly attributable to birth weight. We speculate that poorer growth may be seen in a sub-group of infants with severe BPD. PMID- 2318128 TI - [The formation of carcinogenic nitrosamines from a small amount of precursors in human gastric juice]. AB - It has been shown in vitro with human acidic gastric juice the nitrosomorpholine (NMOR) formation from small doses of precursors (sodium nitrite and morpholine) with a significant difference relative to the control. The presented data suggest the possibility of the nitrosation reaction in the human gastric juice under hypo and anacidic conditions. The data obtained are one more experimental confirmation of the epidemiological evidence of the potential role of nitrates (nitrites) in the etiology of stomach and esophageal cancers. PMID- 2318129 TI - [The effect of environmental factors on the lung cancer morbidity of the population of large cities in the USSR]. AB - Results of the epidemiological study concerning the influence of the air pollution and smoking on the lung cancer incidence in population from 26 cities of the USSR are presented. The analysis of data has shown that smoking and air pollution correlate with the lung cancer incidence. The correlation between air pollution and lung cancer incidence is more significant for men than for women since men have additional professional exposure and smoking habit is more typical of them. PMID- 2318130 TI - [Biometric research in the cytomorphological diagnosis of endometrial lesions]. AB - Morphometrical and optical density (including DNA content) parametres of nuclei of the endometrial epithelial cells in smears of endometrial aspirates obtained from 57 women without endometrial disorders with hyperplastic, precancer conditions and endometrial cancer have been measured by using television image analyzer IBAS-2. Biometrical data have demonstrated a good correlation with cytomorphological diagnostic criteria and in 85.7% they have facilitated discrimination of the normal and hyperplastic epithelium from precancer and high differentiated endometrial cancer. PMID- 2318131 TI - [The capacity of glucocorticoid receptors for activation as a possible criterion of the hormonal sensitivity of human tumors]. AB - For the functional activity evaluation of glucocorticoid receptors (GR) a specific method for their activated form determination was developed on the experimental model of the rat liver. The method is based on the interaction of GR with DNA-cellulose. It has been shown that 26-41% of the total rat liver GR are able of undergoing activation and being bound to DNA-cellulose. Activated GR were studied in 88 renal tumours and in 37 melanomas. 20% of renal tumours and 33% of melanomas contain GR which are not able to undergo activation. The number of activated GR in most cases is much lower than the total GR number. There is no direct correlation between the concentrations of total and activated GR, as well as between the total GR content and the percent of activated forms in the whole receptor pool. It appears that the study of activated GR may give more reliable information about the hormone sensitivity of tumours than the determination of the total receptor content. PMID- 2318132 TI - [The characteristics of lectin binding to the surface of differentiated neuroblastoma C 1300 cells]. AB - Peculiarities of the binding of lectins of castor bean, cochlea, soya bean, lime bean and wheat germs to the surface of differential neuroblastoma C 1300 N 18 cells have been studied using the method electron cytochemistry. It is found that the quantity of the bound lectin conjugates with colloidal gold on the surface of differentiated cells varied considerably from that on the surface of nondifferentiated cells. PMID- 2318133 TI - [The cells of murine sarcoma PC-103 induced by a polymeric plate secret transforming growth factor alpha]. AB - It was shown previously that cells of sarcoma PS-103 induced in mouse by subcutaneous transplantation of plastic film produce growth-stimulating activity. In this communication clone 3 sb, isolated from sarcoma PS-103, was studied. Growth factor produced by the cells of this clone stimulated proliferation of quasi-normal (3T3, NRK) cells and transformed cells both in monolayer and in semi solid medium. It was shown by gel filtration chromatography that the main growth stimulating activity migrated with the protein fraction m.m. 10-15 kDa. The addition of this growth factor to the culture medium significantly (90%) inhibited 125I-EGF (epidermal growth factor) binding by A-431 cells. These data suggest that the growth factor produced by the studied tumor cells is transforming growth factor alpha. PMID- 2318134 TI - [Recombinant tumor necrosis factor promotes the formation of hematogenic metastases to the lungs of C57Bl/6 mice]. AB - The intravenous injection of the recombinant tumour necrosis factor (rTNF) to the C57BL/6 mice at a dose of 10(4) U 1.4 and 24 hours before or 4 hours after the intravenous inoculation of the LL (Lewis carcinoma) or MM-4 (B-16 melanoma) cells was found to be accompanied by a significant increase in the number of hematogenic metastases in the lungs of animals. The above rTNF effect could be considerably inhibited by the single heparin injection. PMID- 2318135 TI - [Endothelial changes in the pulmonary blood vessels of mice with Lewis lung carcinoma and experimental stress]. AB - The influence of surgical tumour removal and of the emotional-pain stress described by Desiderato on the lung metastases development and lung vascular internal surface state was studied in C57BL mice with Lewis carcinoma. Scanning electron microscopy revealed a stress-damaging effect on vascular walls. It is possible to assume that the stress damage of pulmonary blood vessels greatly influences the stimulation of metastases. Concrete mechanisms responsible for this phenomenon are elucidated. PMID- 2318136 TI - [The effect of the combined use of cryosurgery and hyperthermia on an experimental tumor process]. AB - The antitumour efficacy of a single cryosurgery use in combination with hyperthermia was studied in 165 mice with the Lewis carcinoma, sarcoma 180 and 169 rats with Guerin's carcinoma and sarcoma 45. A considerable decrease in the recurrence frequency was observed irrespective of the histological type of the primary tumour. The haemostasis-associated expressed hypoxia has been established to arise in tumour tissues after cryodestruction. A day after the cryodestruction a shift to alkaline pH in the tumour tissue has been observed along with hypoxia. The above conditions possibly specify the high antitumour efficacy of a combined use of the cryosurgery and hyperthermia. PMID- 2318137 TI - [The mechanisms of a decrease in the toxic action of cisplatin when administered jointly with preparation K-2-9 to mice with melanoma B16]. AB - The K-2-9 preparation was determined to change cis-platinum pharmacokinetics, that resulted in its pharmacodynamics alterations. The higher Pt concentrations in the blood of animals which were given the K-2-9 preparation provided selectivity of cytostatic accumulation in the tumour tissue, that was accompanied by more prolonged inhibition of the DNA synthesis. A decrease in the toxicity of cis-platinum is associated with a change in the elimination pathway and acceleration of its removal from the organism. PMID- 2318138 TI - [An evaluation of the toxic and antitumor action of farmorubicin administered to H-strain mice with Ehrlich ascitic cancer]. AB - The toxic and antitumour action of farmorubicin was investigated in experiments on mice. Data on the high antitumor activity were obtained after single application of the drug and at 5-day treatment of mice bearing the Ehrlich ascites tumour. It has been established that farmorubicin used in the tolerant dose was comparatively nontoxic--nonmyelotoxic. At higher doses the toxic damages manifested in different periods and depended on the employed doses. A decrease in the heart weight has permitted revealing the formorubicin-induced cardiotoxicity which was confirmed (after 5 injections of the preparation in a dose of LD 50) by electron microscopy. PMID- 2318139 TI - [The effect of ferromagnet particles on the growth of Walker carcinosarcoma 256 in Wistar rats]. AB - The intravenous injection of ferromagnetic particles (FMP) was studied for its effect on the growth of Walker 256 carcinosarcoma in Wistar rats. The injection of FMP in a dose of 750 mg/kg increased the organism resistance to the tumour development against a background of phagocytic reaction activation in neutrophils. The injection of FMP in a dose up to 2 g/kg inhibited the phagocytic reactions of neutrophils and accelerated the tumour growth. The data obtained evidence that depending on the FMP dose the total reactivity of the organism may either increase or decrease, thus changing, respectively, its resistance to the development of the tumour process. PMID- 2318140 TI - [Changes in the level of the permanent potential of the deep brain structures in rabbits with a Brown-Pearce carcinoma]. AB - Rabbits with the Brown-Pierce carcinoma have been studied in chronic experiments for dynamics of the permanent potential reflecting bioelectrochemical processes in different structures of the hypothalamic and limbic system: medial preoptic area, ventromedial nucleus, posterior hypothalamic area, basal and lateral amygdalas, hippocampus, nucleus coeruleus as well as in central nucleus of the suture. The space-temporal pattern of neurodynamic changes in the subcortical brain structures has been found. These changes correlated with developmental characteristics of the Brown-Pierce carcinoma. PMID- 2318141 TI - The contributions of 131I to the understanding of radiation carcinogenesis. PMID- 2318142 TI - Identification and characterization of an abundant phosphoprotein specific to the large luteal cell. AB - An abundant protein with a relative mol wt of 32K present specifically in the large cells of the pregnant rat corpus luteum has been identified. Separation of large and small luteal cells by elutriation, followed by protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), have revealed that the 32K protein was present as a major protein in the large luteal cells but was practically absent in the small cell population. This protein appears to be highly tissue and cell specific and resolves into three protein species by two-dimensional SDS-PAGE with the major protein having an isoelectric point (pI) greater than or equal to 8.5. It was not detected in preantral follicles or placentas of the same pregnant rats, or in any other tissue examined. After subcellular fractionation, the 32K protein(s) was found in the particulate fraction and was localized principally in the microsomal compartment. Autoradiographic analysis of 35S-amino acid-labeled tissue demonstrated that the 32K protein(s) is synthesized in the corpus luteum. When particulate fractions from small and large cells were incubated in the presence of [gamma-32P]ATP followed by SDS-PAGE, phosphorylation of the 32K protein was apparent. Phosphorylation of this protein was not enhanced by the addition of cofactors for cAMP, Ca2(+)-calmodulin- or Ca2(+)-phospholipid-dependent kinases. Experimental inhibition of steroidogenesis with amino-glutethimide caused a remarkable reduction in the luteal content of this 32K protein whereas estradiol and human CG treatment increased its content. In summary, we have discovered and partially characterized a unique 32K protein(s) which is expressed and phosphorylated only in large luteal cells of the corpus luteum. This protein(s), which is regulated by estradiol formed locally, may serve as a powerful marker for both the large luteal cell and estrogen action in the corpus luteum. PMID- 2318143 TI - Differential effects of continuous and transient treatment with parathyroid hormone related peptide (PTHrp) on bone collagen synthesis. AB - Parathyroid hormone-related peptide (PTHrp), a polypeptide synthesized by tumors associated with hypercalcemia and known to cause bone resorption, was examined for its effects on bone formation in cultures of 21-day fetal rat calvariae. Continuous treatment with PTHrp for 24-72 h stimulated DNA synthesis, but inhibited [3H] proline incorporation into collagen by about 50%. In contrast, transient exposure to PTHrp at 0.1-1.0 nM for 24 h followed by removal of the factor for 48 h caused an increase in [3H]proline incorporation into collagen and noncollagen protein by 2- and 1.6-fold, respectively. The stimulatory effect was seen in the periosteum-free bone, and was decreased, but not prevented by hydroxyurea. PTHrp at 1-10 nM for 24 h increased medium insulin-like growth factor (IGF) I levels by 2.5-4.4-fold, and the effect was sustained 48 h after the removal of the agent. An IGF I neutralizing antibody prevented the stimulatory effect of PTHrp on bone collagen synthesis. PTH had the same stimulatory effects as those of PTHrp on bone collagen synthesis and IGF I concentrations, although slightly lower doses were needed to observe the enhancement of [3H]proline incorporation into collagen. It is concluded that continuous treatment with PTHrp inhibits, whereas transient treatment stimulates, collagen synthesis; the stimulatory effect appears mediated by an enhancement in the local production of IGF I. PMID- 2318144 TI - Influence of calcium on the metabolism of intact parathyroid hormone by isolated perfused rat kidney and liver. AB - The metabolism of synthetic human PTH [PTH-(1-84)] 10(-9) M was studied in isolated rat kidneys and livers, perfused at a calcium concentration of 1 mM or 4 mM. Clearances were measured by an assay specific for intact PTH, and by assays specific for NH2-terminal, mid-molecule, and COOH-terminal immunoreactive PTH (iPTH). Production of PTH fragments was analyzed by HPLC. The kidneys cleared PTH mainly by filtration. The glomerular filtration rate was not lower at 4 mM calcium than at 1 mM calcium, and no significant differences were found between the clearance of PTH at 4 mM and at 1 mM calcium. At 1 mM calcium the kidneys cleared intact PTH without release of detectable fragments. At 4 mM calcium there was significant (P less than 0.05) accumulation of mid-molecule and COOH-terminal iPTH in the perfusate. Both at low and at high calcium the livers cleared NH2 terminal iPTH at the same rate as intact PTH, whereas mid-molecule and COOH terminal iPTH was cleared significantly (P less than 0.005) slower. In the livers, metabolic clearance of PTH was 60% faster at 4 mM calcium than at 1 mM calcium (P less than 0.001). Assuming that the hepatic metabolism of PTH represents degradation of the biologically active hormone and hormone fragments, rather than activation of the hormone, the present results suggest a homeostatic control of PTH degradation in the liver to enhance inactivation of the hormone at high serum levels of calcium. PMID- 2318145 TI - Regulation of glucocorticoid receptor expression: I. Use of a specific radioimmunoassay and antiserum to a synthetic peptide of the N-terminal domain. AB - In order to study glucocorticoid receptor (GR) gene expression at the protein level, we have produced an anti-serum to the GR using a 14 amino acid peptide (14 mer) of amino terminus domain of the human GR, and established a simple and specific RIA to quantitate both the human and rat GR. The antibody was raised in rabbits to the 14-mer coupled to either BSA or keyhole limpet hemocyanin. This antibody immunoblots the Mr = 94,000 bona fide GR in tissue extracts and localizes the GR at the subcellular level by immunocytochemistry. In addition, cytosolic GR, previously labeled by the affinity ligand, [3H]dexamethasone mesylate, was immunoprecipitated by the peptide antibody. The 14-mer was iodinated at its tyrosine residue and used in a standard RIA. The binding of the antibody to the 125I-14-mer was displaced by increasing concentrations of either the 14-mer (standard curve) pure GR or tissue cytosol containing native GR. This RIA reliably detects glucocorticoid receptor level between 20 and 500 fmol/tube in human, rat, and mouse tissues. In two well established cell line systems and their subclones (human CEM and in rat hepatoma tissue culture cells transfected or not with GR cDNA) the GR level, as assessed by this RIA, was compared to GR values using the classical radioreceptor or previously published mRNA assays. The relative amount of GR in wild-type cells and in subclones, as assessed by the novel RIA, was identical to the above-mentioned assays. Using the RIA, we demonstrated the down-regulation of GR level in liver following glucocorticoid administration and its up-regulation following adrenalectomy. This study, which constitutes the first description of an RIA for a steroid receptor using a synthetic peptide, provides a powerful tool for a standardized, sensitive, and simple assay for the GR in human and animal tissues. PMID- 2318146 TI - Effects of tunicamycin on growth hormone binding in rat adipocytes. AB - Digestion of covalently linked [125I]human (h) GH-receptor complexes with neuraminidase or endoglycosidase F reduced the mass of the principal hormone receptor complex from about 130 kilodaltons (kDa) to 120 and 110 kDa, respectively, suggesting that about 20% of the mass of the GH receptor of rat adipocytes consists of N-linked sialocarbohydrates. Incubation of adipocytes with tunicamycin, an inhibitor of N-linked glycosylation, decreased the incorporation of [35S]methionine into membrane glycoproteins by more than 50% in 4 h and decreased specific binding of [125I]hGH by about 70% after 8 h. Decreased binding and incorporation of [35S]methionine were seen only after a lag time of about 2 h. Cross-linking of [125I] hGH to cells that had been treated with tunicamycin resulted in the appearance of a new labeled species of hormone-receptor complex with an apparent mass of about 110 kDa. This band appeared after a delay of about 3 h and reached approximately equal prominence with the 130 kDa band at 5 h. By 8 h, the 110 kDa complex was the predominant band in radioautograms, but some of the 130 kDa species remained. Scatchard analysis of binding data in tunicamycin treated adipocytes indicated that decreased binding of [125I]hGH resulted from a 3- to 4-fold decrease in affinity accompanied by only a small (30%) decline in receptor number. Tunicamycin did not affect the rate of receptor turnover in cells that were also treated with cycloheximide to block protein synthesis, but receptor turnover decelerated with increasing time of incubation. Treatment with tunicamycin for 8 h markedly slowed the rate at which specifically bound [125I]hGH disappeared from adipocytes, suggesting that N-linked carbohydrates may play some role in internalization and processing of labeled hormone. We conclude that 1) N-linked carbohydrates contribute about 20 kDa to the apparent mass of the GH receptor of rat adipocytes; 2) N-linked glycosylation is not required for GH receptors to be inserted into the adipocyte membrane in the proper orientation and to retain their ability to recognize and bind GH; 3) N-linked sugar chains are required for maintenance of a normal high affinity of receptors for GH; 4) N linked carbohydrates are necessary for normal rates of internalization and processing of bound hGH. PMID- 2318148 TI - Changes in the hypothalamo-pituitary-adrenal axis of genetically obese fa/fa rats: a structural, immunocytochemical, and morphometrical study. AB - Most metabolic disorders of genetically obese Zucker rats are reversed by adrenalectomy and are restored by corticosterone treatment, thus suggesting that a functional hypercorticosteronemic state is involved in the pathogenesis of the obesity syndrome in fa/fa rats. However, the hormone content and morphology of the hypothalamo-pituitary-adrenal axis of this animal model have to our knowledge not yet been described. We, thus, investigated morphologically and morphometrically the hypothalamic regions involved in CRF synthesis and secretion in male fa/fa rats. To ascertain if the brain is selectively or uniformly affected, we studied the main nuclei of the lateral and mediobasal hypothalamus, i.e. arcuate, lateral hypothalamic, and ventromedial nucleus and the parvicellular portion of the paraventricular nucleus. Moreover, after immunocytochemical labeling, we analyzed densitometrically the CRF-bearing axons of the median eminence and the ACTH-containing cells of the anterior and intermediate lobe of the pituitary gland. Finally, we investigated the adrenal glands by qualitative light microscopy. In fa/fa rats most hypothalamic nuclei were structurally changed. Furthermore, hypothalamic CRF and anterior pituitary ACTH contents as well as adrenal weight were increased, the zona fasciculata of the adrenal cortex was hypertrophic, and the ACTH content of the intermediate lobe was reduced. In conclusion, our results demonstrate that the obesity syndrome in genetically obese fa/fa rats is associated with lesions of the hypothalamo-pituitary-adrenal axis consistent with hyperadrenocorticism due to hyperactivity of the whole adrenal axis. Alterations also occur in the hypothalamic nuclei controlling glycemia, insulinemia, and circadian corticosterone secretion. PMID- 2318147 TI - Abnormal regulation of the hypothalamo-pituitary-adrenal axis in the genetically obese fa/fa rat. AB - Adrenalectomy has been shown to reverse most facets of the syndrome of the genetically obese fa/fa rat. However, a detailed analysis of the hypothalamo pituitary-adrenal (HPA) axis in these animals is lacking. In the present study, morning corticosteronemia was higher in obese rats of both sexes than in lean ones, whereas evening corticosteronemia was higher only in obese male rats. The HPA axis was further investigated using stressful stimuli. Immobilization, ether, and cold stresses resulted in greater corticosterone levels in obese than in lean animals. These abnormalities consisted in upward shifts of the corticosterone response in obese females and absolute increases in that of obese males, indicating that such alterations were more pronounced in obese male than obese female rats. Due to this, the putative origin of the increased corticosterone output of obese rats was studied in males. Greater levels of ACTH were reached in obese than in lean rats when submitted to a cold stress (6 C). Dexamethasone produced a complete suppression of corticosterone output in both lean and obese rats. During the recovery from such suppression, corticosterone levels rose to higher values in obese than in lean rats. This observation together with the greater cold-induced ACTH output in obese rats suggest that the increased activity of the HPA axis of these animals is of central origin. Whatever its precise etiology within the central nervous system, it is proposed that the increased HPA axis activity in obese rats and its resultant hypercorticism play a role in the establishment and maintenance of their syndrome. PMID- 2318149 TI - The interrelationship of growth hormone (GH), liver membrane GH receptor, serum GH-binding protein activity, and insulin-like growth factor I in the male rat. AB - Indirect evidence suggests that the serum GH-binding protein (GH-BP) is related and possibly derived from the GH-receptor. GH, through its specific receptor, is the major regulator of insulin-like growth factor I (IGF-I) synthesis. The present study was undertaken to correlate serum GH-BP activity with liver plasma membrane GH receptors and their effects on serum IGF-I concentration during spontaneous pulsation of rat (r)GH in the normal male rat and after continuous delivery of human (h)GH to hypophysectomized male rats. In the first set of experiments, 45-day-old male rats were decapitated at 15 min intervals for 4 h. Serum GH-BP levels fluctuated with a 60 min lag behind the rGH levels. IGF-I pulsated over a 3-fold concentration range. IGF-I peak levels coincided with one of the rGH peaks, but its periodicity was longer than 3 h. Taken together with our previous studies on the turnover of the GH receptors, we suggest that each GH surge results in individual pulse-related turnover wave of receptor internalization and recycling. This is accompanied by a parallel increase in serum GH-BP activity. The GH and the receptor wave are responsible for an individual secretion pulse of IGF-I. In the second set of experiments male rats were hypophysectomized at 35 days of age. Four days later osmotic minipumps were implanted for continuous delivery of hGH. After 6 days of hGH treatment the rats were killed, blood was collected for hGH, GH-BP, and IGF-I determination, and the livers were removed. Plasma membranes were prepared, and lactogenic and somatogenic binding of [125I]hGH was evaluated. Removal of endogenous ligand was performed by exposing the membranes to 3 M MgCl2. Continuous administration of hGH induced a dose-dependent increase in liver membrane lactogenic and somatogenic binding. Parallel to that increase, serum GH-BP also increased in a dose-dependent manner, and the correlation between serum GH-BP and the liver membrane receptor was significant. Furthermore, hGH induced a dose-dependent increase in IGF-I concentration. There was a close correlation between IGF-I concentration and liver somatogenic receptors. It is concluded that up-regulation of the liver membrane GH receptors is accompanied by increased GH-BP and IGF-I. In both the pulsation experiment and the continuous infusion experiment, GH-BP closely correlated with the liver membrane GH receptor. PMID- 2318150 TI - Effects of free fatty acids on luteinizing hormone and growth hormone secretion in ovariectomized lambs. AB - The effects of FFA on circulating LH and GH concentrations in ovariectomized ewe lambs were investigated. Lambs (n = 14) were weaned at 2.5 months, ovariectomized at 6.5 months, and used at 8.5 months of age. From weaning until day 0 of the experiment, lambs were fed to maintain body weights (23 kg). On day 0, serum FFA concentrations and mean serum LH concentrations and number and amplitude of LH pulses, as assessed in blood samples collected every 12 min for 4 h, were 6.4 +/- 0.6 mg/100 ml, 0.57 +/- 0.08 ng/ml, 0.45 +/- 0.09 pulses/h, and 0.73 +/- 0.11 ng/ml, respectively. Double the maintenance feeding, beginning day 1, increased (P less than 0.01) body weights by 16% and LH pulse frequency by 82%, but had no effect (P greater than 0.1) on FFA concentrations, mean LH concentrations, or LH pulse amplitude by day 14. On day 14, lambs were infused with lipid (n = 9; 95.8 mg/min) or 0.9% saline solution (n = 5) for 8 h. Blood samples were collected at 12-min intervals for 12 h, beginning 4 h before infusions. FFA levels increased (P less than 0.01) in lipid-infused animals to 27.6 +/- 2.9 mg/100 ml by 4 h of infusion. Mean LH concentrations and LH pulse frequency and amplitude were unaffected (P greater than 0.1) by treatment. In contrast, mean GH concentrations and GH pulse frequency, which were similar (P greater than 0.1) between groups before infusion (14.0 +/- 0.8 ng/ml and 0.36 +/- 0.07 pulses/h, respectively) were decreased by FFA treatment by 51% (P less than 0.01) and 81% (P less than 0.006), respectively. GH pulse amplitude was highly variable and unaffected (P greater than 0.1) by treatment. In summary, elevated FFA levels appear to inhibit the release of GH, but not LH, in the ovariectomized ewe lamb. PMID- 2318151 TI - Stimulation by parathyroid hormone of 45Ca2+ uptake in osteoblast-like cells: possible involvement of alkaline phosphatase. AB - We have investigated the actions of human PTH [hPTH-(1-34)] on the association of 45Ca2+ with two human (SaOS-2 and MG-63) and two rat (ROS 17/2.8 and UMR-106) osteoblast-like cell types. In SaOS-2 cells, hPTH-(1-34) binds to specific membrane receptors to activate adenylate cyclase. Treatment of SaOS-2 cells with hPTH-(1-34) resulted in an increase in 45Ca2+ uptake, in a dose-dependent fashion, up to 2- to 4-fold above control values. The increase was first evident at 10 min and persisted for at least 30 min. Treatment with nimodipine, a calcium channel antagonist, was without effect on the stimulatory action of PTH. A similar enhancement of cell-associated 45Ca2+ was observed when the cells were incubated with vasoactive intestinal peptide, which acts via different receptors to activate adenylate cyclase in SaOS-2 cells. Treatment with (Bu)2cAMP also induced an increase in cell-associated 45Ca2+. Pretreatment of SaOS-2 cells with hPTH-(1-34) for 4 h, which induced homologous desensitization to a second challenge with the same peptide for stimulation of cAMP production, did not attenuate the further enhancement of cell-associated 45Ca2+ by a second treatment with hPTH-(1-34). We then examined a possible relationship between alkaline phosphatase (ALPase) and 45Ca2+ uptake. SaOS-2 cells contained high levels of alkaline phosphatase activity and continuously released the enzyme into the medium. Release was enhanced by treatment with hPTH-(1-34) for 10 min. Incubation of cells with levamisole (an inhibitor of the liver/bone/kidney type of ALPase) resulted in a rapid decrease in basal and PTH-stimulated 45Ca2+ uptake, while treatment with L-Phe-Gly-Gly (an inhibitor of human placental ALPase) was without effect. Treatment of the cells with ALPase (bovine kidney) enhanced 45Ca2+ uptake. In MG-63 cells, a stimulatory effect of hPTH-(1-34) on cell-associated 45Ca2+ was also observed; however, hPTH-(1-34) did not stimulate cAMP production in MG-63 cells. In ROS 17/2.8 cells, neither hPTH-(1-34) nor rat PTH-(1-34) stimulated an increase in cell-associated 45Ca2+, while in UMR-106 cells, rat PTH (1-34) and (Bu)2cAMP did enhance 45Ca2+ uptake, although hPTH-(1-34) was without effect. We conclude that PTH can stimulate an increase in cell-associated 45Ca2+ in several osteoblast-like cell lines, possibly by modulating local ALPase activity; however, this action of PTH does not appear to be obligatorily dependent on the adenylate cyclase-stimulating action of PTH. PMID- 2318152 TI - Two pathways for thyroxine 5'-monodeiodination in brown adipose tissue in fetal sheep: ontogenesis and divergent responses to hypothyroidism and 3,5,3' triiodothyronine replacement. AB - Thermogenesis in rat brown adipose tissue (BAT) is thyroid hormone responsive. Rat BAT expresses a type II 5'-iodothyronine monodeiodinase (5'MDI) which mediates local T3 production from T4. Earlier studies show that BAT from fetal and newborn sheep contains a high Km type I, instead of type II, 5'MDI. To better characterize the 5'MDI of ovine fetal BAT, we studied the in vitro monodeiodination of [125I]T4 at a low substrate concentration (2 nM) and in the presence of 1 mM propylthiouracil in BAT homogenates of control and thyroidectomized fetuses at different gestational ages as well as in newborn lambs. Thyroidectomies were performed at three gestational ages: 99-107 days (group 1), 129-132 days (group 2), and 115-117 days (group 3A). Animals were studied 8-13 days after surgery. A significant increase in the activity of a low Km T4 5'MDI was noted in BAT from hypothyroid fetuses at all three gestational ages. This low Km activity was similar to the type II enzyme in rat BAT and brain in that the activity was also T3 resistant. A gradual rise in BAT type II 5'MDI activity was measured between 99 days gestation and term (150 days). These results indicate that ovine BAT contains two distinct iodothyronine 5' monodeiodinating activities, one with a high Km and another with a low Km. The latter, resembling the type II 5'MDI in rat brain and BAT, is increased in ovine hypothyroid BAT. The former predominates in euthyroid tissue and is similar to the type I 5'MDI characterized in rat liver, kidney, and thyroid. We speculate that BAT type II 5'MDI may be important for neonatal BAT thermogenesis, while the type I enzyme may play a significant role in the increase in serum T3 concentration that occurs at birth. PMID- 2318153 TI - Initial characterization and sexual dimorphism of serum growth hormone-binding protein in adult rats. AB - The in vitro binding of 125I-bovine growth hormone (bGH) to adult rat serum was studied using Ultrogel AcA34 filtration. When analytical chromatography on a 1.6 x 100 cm column was performed, four peaks of radioactivity were revealed: the first two peaks with Mr +/- 220,000 and +/- 110,000 corresponded to bound 125I bGH (abolished by excess of unlabeled bGH), the third corresponded to free 125I bGH and the fourth to free Na125I (Vt). On a short (1 x 40 cm) column, bound 125I bGH eluted as a single peak between the void volume (Vo) and the peak of free 125I-bGH. Serum 125I-bGH binding was specific, saturable, and time-dependent. Specific serum 125I-bGH binding (bound/total radioactivity x 100), calculated as the difference of binding in the absence and the presence of an excess unlabeled bGH, was higher in female than in male rats (26 +/- 2% vs. 11 +/- 1%, respectively; mean +/- SE; n = 6; P less than 0.01). Scatchard analysis revealed a binding affinity of 2 x 10(8) M-1 for both sexes, and a binding capacity of 6.4 x 10(-8) mol/liter for the female rats and 1.6 x 10(-8) mol/liter for the male rats (mean of three serum pools of three animals each). Specific binding of 125I bGH to serum correlated significantly with 125I-bGH binding to liver homogenates (r = 0.83; n = 12; P less than 0.01). These results suggest the presence of a specific GH-binding protein in rat serum and provide further evidence for a close relationship between serum GH-binding protein and hepatic GH receptors. PMID- 2318154 TI - Comparison of reverse triiodothyronine distribution and metabolism in normal dogs and humans. AB - Serum rT3 tracer kinetic studies were performed in 14 normal dogs and 9 normal human subjects. A number of models were used to evaluate the data. Relative rates of hormone degradation by rapidly equilibrating tissues such as liver and kidney and slowly equilibrating tissues such as muscle, skin, and brain could not be determined using serum data alone. Based on known physiology, all hormone losses were confined to rapidly equilibrating sites. Dogs had significantly higher mean serum total rT3 (175% that in man), free fraction of rT3 (437%), and free rT3 levels (765%). Total rT3 values were determined in different assays, due to species differences, which had similar anti-rT3 antiserum characteristics and rT3 standards. Fractional rates of rT3 transfer from serum to both rapidly and slowly equilibrating pools in dogs were not significantly different from those in man, while the fractional transfer rate from the rapid pool to serum was increased (288%). This was associated with significantly smaller rapid and slow pool extravascular binding (rapid, 3.8%; slow, 2.8%), mass (29% and 21%, respectively), and volume (17% and 12%, respectively) in dogs compared to man. In dogs, 31% of the total 0.791 micrograms rT3 was in serum, 29% was in the rapid pool, and 40% was in the slow pool compared to 16% of 2.677 micrograms in serum, 29% in the rapid pool, and 55% in the slow pool in man (P less than 0.01). Further, 89% of the total unidirectional transfer from serum was to the rapid pool, and 11% to the slow pool in dogs compared to 82% and 18%, respectively, in man. Serum clearance (22%) and appearance rates (39%) as well as maximum total body production rates (34%) of rT3 were lower in the dogs. Serum appearance and maximum production rates, and hormone masses in the rapid and slow pools were no longer significantly different between dogs and man when normalized for either body weight or body surface area. Serum volume was no longer significant when normalized for body surface area. Noncompartmental analysis resulted in a significant underestimation of the mean total fraction rate of hormone exit from serum (by 20%), total volume of distribution (10%), extravascular binding (18%), and mean residence time (11%) in dogs and of extravascular binding (22%) in man. The serum appearance rate of rT3 was 78% of the maximum total body production rate in dogs and 69% in man.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2318155 TI - Hysterectomy-induced alterations in prolactin secretion of lactating rats. AB - The contribution of the uterus to the regulation of PRL secretion in lactating dams and cycling female rats was investigated. Lactating animals were hysterectomized or sham operated 2 days after parturition, and the number of pups was adjusted to eight. Blood samples for PRL RIA were obtained through intra atrial cannulae implanted 2 days before experimentation. In order to study the PRL secretory profile in undisturbed freely lactating rats, blood samples were taken every 2 h for 24 h starting at 1400 h. During early lactation (days 7-8), hysterectomy did not alter the PRL secretory profile compared to that of sham operated controls. On days 14-15 post partum, PRL secretion followed a characteristic bimodal pattern showing two PRL surges at 1800 h and 0600 h. After hysterectomy, the early morning PRL surge disappeared and PRL secretion showed an unimodal daily rhythm reaching its peak at 1800 h. The possible effect of the absence of the uterus on suckling-induced PRL release at various stages of lactation was studied. On days 7-8, suckling stimuli after 4 h of pup deprivation induced robust PRL release. Hysterectomy did not significantly alter PRL release at this earlier stage of lactation. In control groups, the suckling-induced PRL secretory response markedly declined as the postpartum period advanced. On the other hand, the hysterectomized animals retained significantly greater responsiveness to suckling during the second half of lactation. These data indicate an inhibitory influence of the uterus on PRL secretion. The onset of this uterine effect is considerably delayed, and its influence became prominent only at a later phase of lactation. The effect of length of pup deprivation preceding the suckling stimulus, in combination with hysterectomy, was also investigated. Hysterectomy significantly increased suckling-induced PRL release after 4 and 24 h separation compared to the sham-hysterectomized animals. When the separation was longer than 48 h, the inducibility of PRL release by suckling declined and was not influenced by hysterectomy. In order to study the possible influence of the uterus on PRL secretion during the estrous cycle, regularly cycling female rats were hysterectomized at diestrus 1. Twelve days later the animals were cannulated, and serial blood samples were taken during the subsequent proestrus. Hysterectomy did not alter the PRL surge which occurred on the afternoon of proestrus indicating that the uterus does not have a major function in regulating PRL secretion on proestrus. In conclusion, hysterectomy significantly delayed the extinction of suckling-induced PRL release revealing the active role of the uterus in the regulation of this neuroendocrine reflex. PMID- 2318156 TI - The response of splenic lymphocytes removed from hypophysectomized orchidectomized hamsters to phytohemagglutinin correlates with somatic growth but not with circulating prolactin levels. AB - To examine the relationship between PRL and the mitogenic capacity of lymphocytes, we studied the relationships among circulating PRL levels, somatic growth, and the response of splenic lymphocytes to the mitogen phytohemagglutinin (PHA) in hamsters. In the first experiment, no differences were observed in the PHA responses of lymphocytes removed from intact or hypophysectomized orchidectomized hamsters. No relationships were observed between circulating PRL levels and either the PHA responses or somatic growth. However, significant positive correlations were observed between the somatic growth of intact or hypophysectomized-orchidectomized hamsters and the PHA responses (r = 0.741; P less than 0.01 for intact hamsters; r = 0.642; P less than 0.01 for hypophysectomized-orchidectomized hamsters). In three subsequent experiments we tested the effects of placing muscle or hypophysial allografts in hypophysectomized-orchidectomized hamsters on somatic growth, the PHA responses, and circulating PRL levels. Neither type of allograft altered the somatic growth of hypophysectomized-orchidectomized hamsters. The hypophysial allografts did elevate serum PRL levels. In all experiments the responses of splenic lymphocytes to PHA showed a significant positive correlation with somatic growth, but not with serum PRL levels. These results minimize a role of PRL in this particular lymphocyte response. The results suggest that a strong correlation exists between mechanisms responsible for somatic growth in hypophysectomized-orchidectomized hamsters and the immune status, as determined by the response to PHA, of the animals. This relationship also may exist in intact hamsters. PMID- 2318157 TI - Effect of maternal fasting on fetal growth, serum insulin-like growth factors (IGFs), and tissue IGF messenger ribonucleic acids. AB - Pregnant rats were fasted or allowed access to ad libitum feeds for the last 3 days of gestation to determine if the fetal growth retardation that results from maternal nutrient deprivation correlates with reductions in serum insulin-like growth factor-I (IGF-I) and IGF-II. In addition, IGF-I and IGF-II mRNA concentrations in liver and lung were measured by specific solution hybridization assays to determine if changes in steady state levels of mRNA correlate with changes in serum values. Fetal serum IGF-I concentrations were 30% lower in fasted than in control fetuses, although fasting did not significantly reduce the abundance of IGF-I mRNA in their livers or lungs. Serum IGF-I concentrations in the fasted dams were 34% lower than those in controls. IGF-I mRNA concentrations in the livers and lungs of the fasted dams were also lower than those in controls and correlated with serum IGF-I values (liver: r = 0.833; P less than 0.001; lung: r = 0.610; P less than 0.05). Therefore, whereas IGF-I appears to be transcriptionally regulated by fasting in dams, regulation of circulating IGF-I in fetuses may occur at a post-transcriptional step. Serum IGF-II and liver IGF II mRNA concentrations were much higher than IGF-I levels in the fetuses and were not influenced by maternal fasting. Dam serum IGF-II concentrations were low compared to those in fetal serum and also were not reduced by fasting. We conclude that one mechanism by which maternal malnutrition causes intrauterine growth retardation is through decreased expression of IGF-I. On the other hand, short term nutrient restriction does not appear to be a regulator of IGF-II during either fetal or adult life. PMID- 2318158 TI - Oxytocin- and vasopressin-binding sites in the rat uterus: competition binding and inhibitory pA2 studies with oxytocin and oxytocin antagonists. AB - Recent reports have presented evidence suggesting that there are distinct oxytocin (OT) and vasopressin (VP) receptors in the human and rabbit myometrium. In this study we have investigated whether OT and arginine vasopressin (AVP) activate the same or two different receptor systems in the rat uterus in producing their uterotonic action and whether the myometrial OT/VP receptors are similar to the V1 receptors in the vascular smooth muscle cells. We compared the dose-response characteristics of OT and AVP by the in vitro cumulative dose response curve technique. We determined the ligand-receptor binding characteristics of [3H]OT and [3H]AVP on uterine membrane fractions from nonpregnant and pregnant rats. Specific OT antagonists were used in competition receptor binding assays and in antioxytocic pA2 bioassays against OT and AVP to determine whether OT antagonists can discriminate between OT- and AVP-binding sites in the myometrium. We also compared the in vitro antioxytocic (OT receptor mediated action) and the in vivo antivasopressor (V1 receptor-mediated action) potencies of a series of six OT antagonists. Our results show that OT- and AVP binding sites in the nonpregnant rat uterus have similar binding characteristics and cannot be distinguished by the dose-response study, radioligand receptor binding assays, or OT antagonists in the competition binding and pA2 assays. However, in the term pregnant parturient uterus, the two binding sites can be clearly differentiated. OT receptor density, but not AVP, was markedly increased at term pregnancy. All six OT antagonists studied in this investigation were more potent in antagonizing the uterotonic response to OT than the vasopressor response to AVP. The antioxytocic:antivasopressor potency ratios, however, were different between the antagonists, ranging from nearly equal (0.91) to low (0.1). The results above suggest that there are distinct OT- and AVP-binding sites in the rat myometrium. The myometrial OT/AVP receptors are similar to but not the same as the V1 receptors in the vascular smooth muscle cells. PMID- 2318159 TI - Vectorial secretion of prostaglandins by polarized rodent uterine epithelial cells. AB - Uterine epithelial cells (UEC) isolated from mature mice as well as immature mice and rats were cultured on EHS matrix-coated nitrocellulose filters in order to determine their ability to secrete prostaglandin (PG) F2 alpha and PGE2 in a polarized manner. Ultrastructural analyses were performed to validate the polar nature of mouse UEC and demonstrate the presence of separate apical and basolateral plasma membrane domains. These properties included the presence of tightly juxtaposed lateral membranes, apical microvilli, and a relatively flat basal surface. Biochemical indices of polarity included the preferential (approximately 5:1) basal uptake of [35S]methionine as well as a preferential (approximately 9:1) apical secretion of protein. UEC isolated from mice during the estrous and diestrous stages of the estrous cycle did not differ in their degree of polarity, as measured by these morphological and biochemical indices. UEC of estrous and diestrous mice as well as immature mice and rats preferentially secreted PGF2 alpha to the basal medium to an approximately 4-fold greater extent than to the apical medium. PGE2 was secreted at least 10-fold less than PGF2 alpha, and a preferential basal secretion could not be demonstrated. Polarized UEC accumulated relatively large cellular pools of PGF2 alpha, while nonpolarized cells grown on matrix-coated plastic did not. This difference was reflected by the inability of an inhibitor of PG biosynthesis, indomethacin, to inhibit PGF2 alpha secretion by polarized cells during short (4-h) incubations. In contrast, this drug effectively inhibited secretion in nonpolarized cells or polarized cells incubated with indomethacin for longer (24-h) intervals. Therefore, cellular PGF2 alpha pools apparently support continued secretion of this lipid even when de novo synthesis is transiently inhibited. Preferential basal secretion of PGF2 alpha was due to the polar nature of UEC, since disruption of tight junctions with EGTA modified the basal to apical ratio of PGF2 alpha secretion to near unity. Sodium azide inhibited the secretion of PGF2 alpha, indicating that PGF2 alpha secretion was energy dependent. PGF2 alpha secretion was not coupled to protein synthesis or secretion, since cycloheximide did not inhibit this process in polarized or nonpolarized cells. These studies describe the first evidence for polarized secretion of lipid-derived hormones by epithelial cells. The preferential basal secretion of PGF2 alpha may play an important role in regulating UEC interactions with the underlying stroma. PMID- 2318161 TI - Cell-free interaction of the estrogen receptor with mouse uterine nuclear matrix: evidence of saturability, specificity, and resistance to KCl extraction. AB - An integral part of the mechanism of estrogen action is the interaction of estrogen receptor (ER) complexes with specific nuclear acceptor sites to effect alterations in genomic expression. The localization of nuclear acceptor sites has been in question, but an increasing body of indirect evidence implicates the nuclear matrix. To assess the binding characteristics of [3H]estradiol-receptor complexes (3HER) to nuclear matrix, ER from ovariectomized mice was partially purified by ammonium sulfate precipitation and incubated under cell-free conditions with mouse uterine nuclear matrix at 4 C. The binding capacity of the nuclear matrix was determined to be 36.4 +/- 5.7 fmol/100 micrograms DNA, with a Kd of 0.23 +/- 0.03 nM. Binding to nuclear matrix sites was specific, as determined by the ability of increasing concentrations of unlabeled ER complexes to inhibit binding of 3HER. Spleen, used as a nontarget tissue, contained fewer binding sites (n = 4.07 fmol/100 micrograms DNA) than matrix from liver (n = 14.2). The binding affinity was the same in all three tissues. Injection of animals with estradiol before death was associated with loss of assayable nuclear matrix binding sites, implying occupancy of sites by ER in vivo. Unbound receptor (R) also demonstrated the ability to bind to uterine matrix (n = 40.2 +/- 2.7 fmol/100 micrograms DNA; Kd = 0.26 +/- 0.05 nM) as well as to competitively inhibit the binding of 3HER complexes. However, heat-inactivated receptor displayed no binding or competing activity, nor did the progesterone receptor. The two forms of the receptor can be functionally distinguished by extraction with 0.6 M KCl; 43% of ER, but no R, were resistant to KCl extraction. These results indicate that nuclear acceptor sites are associated with the nuclear matrix. Furthermore, these sites demonstrate the criteria expected of specific binding sites, i.e. high affinity, limited capacity, hormone receptor, and relative tissue specificity. The apparent association of uncomplexed receptor to nuclear acceptor sites may explain the uterine tissue nuclear localization of ER in the absence of hormone. PMID- 2318160 TI - Apolipoprotein A-IV messenger ribonucleic acid abundance is regulated in a tissue specific manner. AB - The influence of development and estrogen, thyroid hormone, corticosteroid, and fibrate administration on apolipoprotein (apo) A-IV mRNA levels in the liver and intestine and on serum or plasma concentrations of apo A-IV was studied in the rat. Treatment of ovariectomized rats with ethinyl estradiol provoked a dose dependent decrease in liver apo A-IV mRNA levels, whereas intestinal apo A-IV mRNA did not change. The serum apo A-IV concentration decreased in a dose dependent manner. Administration of L-T4 increased liver apo A-IV mRNA levels more than 2-fold, while n-propylthiouracil (PTU) decreased these levels more than 4-fold. Intestinal apo A-IV mRNA levels remained constant upon L-T4 treatment, but increased after PTU. Change in thyroid hormone levels caused no significant alteration of plasma apo A-IV levels. Hydrocorticsone increased liver and intestinal apo A-IV mRNA levels 2- and 1.5-fold, respectively, without changing plasma apo A-IV. Liver and intestinal apo A-IV mRNA underwent opposite changes during development. Intestinal apo A-IV mRNA decreased gradually during the period of weaning, while liver apo A-IV mRNA was undetectable before day 20 of life and rose to adult levels thereafter. Both L-T4 and hydrocortisone were able to increase liver apo A-IV mRNA prematurely when rat pups were treated from day 9 on. Hypothyroidism induced by PTU, on the other hand, was able to delay the developmental rise in liver apo A-IV mRNA. The hypolipidemic drug clofibrate reduced liver apo A-IV mRNA more than 10-fold without changing the intestinal levels. Plasma apo A-IV decreased by one third. Ethinyl estradiol, thyroid hormones, and clofibrate regulate apo A-IV mRNA abundance in a tissue-specific manner. Only liver, not intestinal, apo A-IV mRNA levels respond to treatment. Furthermore, opposing changes in liver and intestinal apo A-IV mRNA levels occur during development, and thyroid hormones and glucocorticoids are able to accelerate the developmental changes in liver apo A-IV mRNA. PMID- 2318162 TI - Tolerance and cross-tolerance to stress-induced increases in plasma Met enkephalin in rats with adaptively increased resting secretion. AB - Plasma concentrations of both native (pentapeptide plus its sulfoxide) and peptidase-derivable (trypsin followed by carboxypeptidase-B) Met-enkephalin showed brisk increases in response to the stresses of immobilization, hemorrhage, and electric footshock in conscious, freely moving, adult male rats. Daily exposure to 150-min periods of immobilization resulted in a maintained increase in baseline plasma concentrations of native Met-enkephalin 21.5 h after the sixth day and a further increase after 39 days. The plasma native Met-enkephalin response to acute immobilization was attenuated on day 7 and completely absent on day 40. Unstressed rats showed a plasma native Met-enkephalin response to hemorrhage of 15% blood volume and a further increase in response to 25% hemorrhage. Immediately after initial acute immobilization or 6 days of daily immobilization when plasma native Met-enkephalin was elevated but the response to acute immobilization was attenuated, plasma native Met-enkephalin responses to hemorrhage were also attenuated. Rats that had been immobilized daily for 40 days and showed no plasma native Met-enkephalin response to acute immobilization also showed no responses to hemorrhage. After 39 days of immobilization when there was no plasma native Met-enkephalin response to acute immobilization, there was also no response to footshock. Thus, development of tolerance or adaptive loss of plasma native Met-enkephalin response to immobilization with repeated exposure to this stressor is associated with cross-tolerance or adaptive loss of the responses to the stresses of hemorrhage or electric footshock. Development of tolerance and cross-tolerance of plasma responses of peptidase-derivable Met enkephalin paralleled that of native Met-enkephalin. Thus, adaptation of plasma Met-enkephalin responses to repeated exposure to a stressor included both increased resting secretion and decreased acute responses to homotypic or novel stressors. PMID- 2318163 TI - Activin-A inhibits oxytocin and progesterone production by preovulatory bovine granulosa cells in vitro. AB - The aim was to examine the effect of activin on luteinization of preovulatory bovine granulosa cells in vitro. Bovine activin-A was found to inhibit the production of oxytocin (OT) and progesterone by bovine granulosa cells from individual preovulatory follicles cultured in serum-free medium. The minimal response on OT production (25% inhibition) occurred with 0.1-1 ng/ml activin-A, and the maximal inhibition (83%) occurred with 10 ng/ml activin-A after 2-3 days in culture. Progesterone showed a similar response (30% inhibition for 0.1-1 ng/ml and 74% for 10 ng/ml). Inhibin production was not consistently effected by activin-A. Inhibin (75 U/ml) had no detectable effect upon OT or progesterone production. When activin-A was withdrawn from the cell culture after 72 h and the incubation continued for a further 72 h, a recovery in OT was seen on day 4 and 5 after activin-A doses of 0.1-1 ng/ml, but not after higher doses (3 and 10 ng/ml). Progesterone did not show a recovery, but the levels remained constant for 3 days (0.1 and 0.3 ng/ml activin-A) or for 1 day (1-10 ng/ml activin-A) and then fell to control levels by day 6 of culture. We conclude that bovine activin A has an autocrine action on bovine granulosa cells in vitro, to inhibit basal production of OT and progesterone, consistent with the role of activin-A in delaying the process of luteinization. PMID- 2318164 TI - Rat brain natriuretic peptide--tissue distribution and molecular form. AB - Using an antiserum against the ring structure of rat brain natriuretic peptide (rat BNP), we have established a specific radioimmunoassay (RIA) for rat BNP and elucidated its tissue distribution and molecular form. Rat BNP-like immunoreactivity (-LI) was detected in the highest amount in cardiac extracts (574.0 +/- 138.8 pmol/g in the atrium and 4.3 +/- 1.1 pmol/g in the ventricle). The secretory rate of rat BNP-LI from the perfused whole heart was 50.0 +/- 1.9 fmol/min, about 60% of which was maintained even after atrial removal. We also detected rat BNP-LI throughout the spinal cord (134-175 fmol/g), although no detectable amount was present (less than 100 fmol/g) in other tissues including the brain. High performance-gel permeation chromatography and reverse phase-high performance liquid chromatography coupled with the RIA revealed that rat BNP with 45 amino acids is a major storage form as well as a secretory form of rat BNP-LI in the heart. The major component in the spinal cord was also rat BNP. These findings indicate that the tissue distribution and the processing pattern of rat BNP are different from those of atrial natriuretic peptide and porcine BNP, thereby suggesting the presence of complicated diversity of the natriuretic peptide system. PMID- 2318165 TI - Effects of repetitive activation and changes in external ionic environment on hippocampal CA1 pyramidal cell afterhyperpolarizations. AB - Afterhyperpolarizations (AHPs) in hippocampal CA1 pyramidal neurons known to be generated predominantly by a Ca-dependent K conductance were examined to see if they could be inverted by changes in extracellular potassium of the magnitude observed during interictal or ictal discharges and for their liability during repetitive activation under normal ionic conditions or in the presence of elevated extracellular potassium and decreased extracellular calcium. Under all circumstances tested, the AHP remained hyperpolarizing and was associated with a conductance increase. Thus, the very liable hyperpolarizing event that follows a depolarizing shift in hippocampal pyramidal neurons in various epileptic foci (which disappears early during the transition between interictal and ictal activity) probably is not due to the same mechanism as that which underlies the AHP. PMID- 2318166 TI - Feline amygdaloid kindling and the sleep-waking pattern: observations on daily 22 hour polygraphic recording. AB - For 22 h daily, polygraphic examination was made of sleep organization in four cats, both before and after amygdaloid (AM) kindling. After the completion of AM kindling and repetitive induction of kindled convulsion, the percentage of time spent in rapid eye movement sleep (REMS) significantly decreased, while the total sleep time (TST) remained unchanged. REMS suppression was most profound during the immediate postictal hours and continued through the 22-h period without a rebound increase. Slow wave sleep (SWS) was also suppressed during the postictal hours; however, this suppression was exceeded by that of REMS and was followed by a rebound increase. These changes in sleep organization were transient. During a rest interval of 2 months without kindled convulsions, they gradually disappeared and there was a complete recovery to the prekindling baseline. However, when the AM-kindled convulsion was reintroduced, there was an abrupt REMS suppression without TST change. We conclude that changes in sleep organization after AM kindling are (a) characterized by suppression of REMS and a compensatory increase in SWS, and (b) a direct but transient correlate of convulsion rather than of an acquired seizure susceptibility. PMID- 2318167 TI - Effects of subcutaneous injections of zinc chloride on seizures induced by noise and by kainic acid. AB - Several lines of evidence implicate zinc in the pathogenesis of epileptic seizures, and administration of zinc salts has been shown to affect seizure susceptibility. In the present work, we studied the effects of subcutaneous (s.c.) injections of ZnCl2 on seizures induced by intraperitoneal (i.p.) kainic acid (10 mg/kg) in rats and by noise (80-120 dB) in the DBA/2J mouse. Previous administration of zinc salt (20-200 mg/kg) substantially reduced the frequency of noise-induced running fits, clonic and tonic seizures, and deaths in mice, but had no significant effect on the incidence or severity of kainic acid-induced seizures in rats. Together with findings in the literature, our results suggest that zinc plays multiple, sometimes antagonistic roles in seizure development. PMID- 2318168 TI - Intracarotid amobarbital (Wada) test for language dominance: correlation with results of cortical stimulation. AB - Eighty-eight patients had bilateral intracarotid amobarbital (Wada) testing to determine hemispheric dominance for language in preparation for epilepsy surgery, as well as unilateral extraoperative cortical electrical stimulation using subdural electrode arrays. In none of the patients with left dominance by Wada testing were language areas found with right-sided stimulation, but two patients with right dominance by Wada testing had language areas mapped on the left side. These findings suggest that left dominance by Wada testing is strong evidence for exclusive lateralization of language function in the left hemisphere, but there is concern about the ability of the Wada test to exclude the possibility of some left-sided language function despite apparent right-sided dominance. Patients with left dominance on Wada testing do not need cortical stimulation before extensive right temporal lobectomy, but we believe that patients with right or bilateral dominance on Wada testing should have cortical stimulation for localization of language areas if extensive left or right temporal or frontal resection is planned. PMID- 2318169 TI - Cardiac and respiratory correlations with unit discharge in epileptic human temporal lobe. AB - We recorded respiratory activity and electrocardiogram (ECG) together with single cell activity from the amygdala and hippocampus of epileptic patients who later received anterotemporal lobectomy. Cross-correlation histograms were used to test for neuronal discharge timing relationships with inspiration or ECG. Linear regression was used to test for correlations of inspiratory time, respiratory period, and heart rate (HR) with tonic unit rate for each breath. Of 129 cells from 16 patients who later had resection, 89 were contralateral and 40 were ipsilateral to the resected lobe. Of the contralateral cells, 19% had a timing relationship with the cardiac cycle and only 1% had such a relationship with the respiratory cycle. Tonic correlations with HR were noted in 22% and with respiratory period and inspiratory time in 11 and 6%. Neither these percentages nor mean discharge rate differed between structures, although variance in rate was much higher on the resected side. Amygdala cells on the resected side showed more correlations with the cardiac cycle (55 vs. 20%), respiratory period (46 vs. 3%), and inspiratory time (27 vs. 7%) and were more likely to show several types of correlation. The results suggest a selective loss of ipsilateral amygdala cells and/or afferents, favoring relationships with cardiac- and respiratory related systems and a possible synaptic reorganization of remaining cardiorespiratory afferents. PMID- 2318170 TI - Survey of public awareness, understanding, and attitudes toward epilepsy in Henan province, China. AB - The awareness, understanding, and attitudes toward epilepsy in 1,278 men and women were surveyed in Henan, China in 1988. Results showed that 93% had read or heard about epilepsy; 77% knew someone who had epilepsy; 72% had seen someone who was having a seizure; 57% would object to having their children associate with persons with epilepsy in school or at play; 87% would object to having their children marry a person with epilepsy; 53% believed that epileptic persons should not be employed in jobs as other persons are; 16% believed that epilepsy was a form of insanity; 40% did not know the cause of epilepsy; 10% did not know what an epileptic attack was like; and 17% did not know what to recommend if their friends or relatives had epilepsy. The relationship between the responses and the respondents' age, sex, marital status, number of offspring, level of education, occupation, and residence was analyzed. Education reduced the respondent's prejudice against play and employment, but did not change their objection to marriage and appeared to have reinforced their linking epilepsy with insanity. As compared with the surveys conducted in Western countries, our survey showed that awareness of epilepsy in China was greater, if not the same, but the attitudes toward epilepsy were much more negative. PMID- 2318172 TI - Changes in plasma progesterone concentrations from days 17 to 42 of gestation in mares maintaining or losing pregnancy. AB - Plasma progesterone concentrations were measured in 179 mares bled on alternate days commencing with a positive pregnancy diagnosis on Days 17 to 18 after ovulation and concluding on Days 42 to 45. During this period 17 mares (10 per cent) lost their pregnancies, 11 before Day 25. In 15 mares the timing of the pregnancy loss could be determined with adequate accuracy; in only one did a decline in progesterone precede the loss. Thus pregnancy loss between Days 17 and 42 was rarely caused by a fall in plasma progesterone. PMID- 2318171 TI - Effect of phenobarbital on carbamazepine and its major metabolites in serum, different brain areas, and urine after acute and chronic administration to rats. AB - The influence of coadministration of phenobarbital (PB) on disposition of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) in serum and in discrete areas of rat brain, together with its effects on urinary excretion of CBZ, CBZ-E, and trans-10,11-dihydro-10,11-dihydroxycarbamazepine (CBZ-DIOL) were investigated after both acute and chronic administration. Acute coadministration of PB resulted in increased serum CBZ levels, whereas serum CBZ-E levels were initially lower and then higher. In daily urinary excretion, a reduction in both CBZ-E/CBZ ratio and CBZ-DIOL/CBZ ratio was observed. Chronic (30 day) coadministration of PB led to a decrease in serum CBZ levels after the first hour, whereas serum CBZ-E levels were initially higher and then lower. In daily urinary excretion, a decrease in CBZ-E/CBZ ratio and an increase in CBZ-DIOL/CBZ ratio were noted. These results are consistent with an inhibitory interaction and a metabolic induction on both CBZ epoxidation and CBZ-E metabolism in acute and chronic administration, respectively. However, effects on CBZ epoxidation were preferential. In the various brain areas, the effects observed were similar to those noted in serum. In addition, a relevant increase in brain/serum CBZ ratios was observed with chronic coadministration of PB. PMID- 2318173 TI - Arthrography of the equine shoulder joint. AB - Techniques and normal radiographic anatomy for positive and double contrast shoulder arthrography in horses were evaluated. General anaesthesia was used for most radiographic projections of the shoulder. The mediolateral projection provided the most information during arthrography, although the supinated mediolateral view occasionally allowed better definition of the cartilage surfaces on the medial aspects of the humeral head. The craniocaudal mediolateral oblique and caudocranial projections provided limited additional information. Water soluble non-ionic contrast agents, such as metrizamide and iohexol, were suitable for shoulder arthrography; iohexol resulted in less synovitis and lameness. Arthrography in cases of osteochondrosis and osteochondritis dissecans allowed better evaluation of cartilage attachment to subchondral bone, better evaluation of the length and depth of cartilage lesions and more accurately defined the site and shape of osteocartilaginous free bodies. Cartilage thickening without detachment from the subchondral bone could only be determined by arthrography. Although these thick cartilage regions may later dissect from the subchondral bone, most cases where the cartilage was firmly adherent were not candidates for surgical debridement and carried a favourable prognosis. The determination of a free flap by arthrography indicated the need for surgery. Extensive humeral and glenoid cavity lesions were better defined by arthrography, allowing a rational decision between surgical debridement or euthanasia. Using arthrography, evaluation of the size and patency of the communicating canal to a subchondral cystic defect better separated cases with long, narrow and poorly patent canals for conservative rather than surgical therapy. PMID- 2318174 TI - Impedance plethysmography. AB - The technique of impedance plethysmography is described and its application to observation of lung volume changes in the horse at exercise is discussed. The results from horse at rest show that there is a close relationship between rate of lung volume change (flow rate) and the associated impedance changes during both inspiration and expiration. Impedance changes during exercise were related to inspiration and expiration by observation of associated respiratory sounds. Artefacts related to technical difficulties are also indicated. PMID- 2318176 TI - A comparison between chromium-mordanted hay and acid-insoluble ash to determine apparent digestibility of a chaffed, molassed hay/straw mixture. AB - The apparent digestibility of a molassed, chaffed grass hay/straw mixture was determined using four mature horses (mean weight 606 kg). Animals were stalled individually and kept on rubber mats. A preliminary feeding period of 18 days was followed by a 10 day collection period. Chromium-mordanted hay was given before the first feed at 08.00 h and subsequent meals were at 12.00, 16.00 and 20.00 h. On Days 3 and 10 of the collection, all faeces were sampled over a 24 h period. In addition, throughout the 10 day collection, faecal material was sampled at 10.00 and 16.00 h. The mean (+/- se) chromium recovery was 96.5 per cent +/- 0.76 and the hay/straw mixture contained 7 MJDE/kg dry matter and 15.1 g DCP/kg dry matter. There was no significant difference between the methods used to estimate apparent digestibility although chromium measurements consistently underestimated whilst acid-insoluble ash consistently overestimated digestibility values. There was a large variation in faecal chromium concentration for each horse over a 24 h period compared to acid-insoluble ash concentrations and, consequently, indirect estimates of apparent digestibility of nutrients in the equine are prone to large errors if chromium is used as a marker. If total faecal collection is impractical, acid-insoluble ash is the preferred indirect marker for the estimation of apparent digestibility coefficients for nutrients in horses. PMID- 2318175 TI - Equine urine pH: normal population distributions and methods of acidification. AB - Our investigation of the urine of grazing horses at the University of Kentucky shows that the mean pH level is about 7.9, and if their diet is supplemented with grain, it is about 7.4. There appears to be no significant effect of time of day or year on urine pH levels in horses. However, horses taken from pasture and supplemented with grain in a stalled environment show a slight decrease in urine pH. Additionally, we investigated the effects of storage on pH levels. Equine urine samples appear to be quite stable with regard to pH for 48h, but then show a marked increase. Urine pH can have a great effect on the urine concentration of some drugs and therefore, uncertainties can arise when data generated in grazing horses are compared or extrapolated to racing horses whose urine pH can be quite low. In an effort to simulate the drop in urine pH seen in some racing horses, we examined the effects of ammonium chloride, ascorbic acid, lactic acid and methionine on urine pH in research horses. Both oral and intravenous routes of administration were used. Although all agents tested showed varying degrees of efficacy, oral administration of ascorbic acid proved to be the safest and most effective agent to model the rapid acidification of urine seen in post race samples. PMID- 2318177 TI - Failure to demonstrate reperfusion injury following ischaemia of the equine large colon using dimethyl sulphoxide. AB - A study was undertaken to evaluate the significance and mechanism of reperfusion injury in the equine large colon following 1 h of haemorrhagic strangulation obstruction (HSO) or ischaemic strangulation obstruction (ISO) and to assess the effect of treatment with dimethyl sulphoxide (DMSO). ISO or HSO were created 40 cm from the pelvic flexure and maintained for 60 mins under general anaesthesia. Normal saline or 20 per cent DMSO (1 g/kg bodyweight) was administered intravenously 10 mins prior to the end of the ischaemic period. Four groups of four horses in a 2 x 2 factorial design were used. Treatments of HSO or ISO and DMSO given (yes or no) were utilised. Intestinal wall biopsies and right colic arterial and venous blood samples were taken at 0, 60, 90 and 120 mins following initiation of the obstructions. Histological evaluation of the intestine using haematoxylin and eosin stained sections and immunohistochemical staining for albumin were performed. Mucosal and serum reduced glutathione (GSH) and oxidised glutathione (GSSG) levels and the amount of lymphatic dilatation with albumin and submucosal pooling of albumin were used as indirect measures of oxygen free radical production. Histopathological changes were minimal after 1 h of either type of ischaemia. Progressive changes during the post ischaemic period were minimal for ISO and moderate for HSO. Serum GSH and GSSG levels were not detectable. There was no demonstrable benefit of DMSO treatment as assessed by histology, immunohistochemistry or preservation of GSH levels in the mucosa. In conclusion, a reperfusion injury following 60 mins of ischaemia could not be detected in this study. PMID- 2318178 TI - Contrast radiography of the equine oesophagus: effect of spasmolytic agents and passage of a nasogastric tube. PMID- 2318179 TI - The effect of artificial occlusion of the Ramus navicularis and its branching arteries on the navicular bone in horses. PMID- 2318180 TI - Fluphenazine induced Parkinson-like syndrome in a horse. PMID- 2318181 TI - Antisperm antibodies in the semen of a stallion following testicular trauma. PMID- 2318182 TI - Management of intracortical fractures of the palmaroproximal third metacarpal bone in a horse by surgical forage. PMID- 2318183 TI - Infertility of autoimmune origin in a stallion. PMID- 2318184 TI - Immune related infertility in stallions? PMID- 2318185 TI - Heat production and its clinical implications in neonates. PMID- 2318186 TI - A scanning electron microscopical study of the dermal microcirculation of the equine foot. AB - The microcirculation of the dermal laminae and papillae of the equine foot from seven clinically normal Australian ponies was studied using an improved microvascular casting corrosion technique and scanning electron microscopy. Casts of veins, arteries, capillaries and arteriovenous anastomoses (AVAs) were readily identified by their characteristic surface morphology. Arteries entered the laminar circulation axially, between pairs of axial veins, and were connected to each other by smaller calibre interconnecting arteries. Short abaxial branches of the axial interconnecting arteries gave rise to tufts of predominantly, proximodistally orientated, capillaries arranged abaxially in rows. The laminar veins anastomosed with each other extensively (the axial venous plexus) and formed most of the vascular skeleton of casts of the dermal laminae. AVAs were found throughout the laminar circulation but the largest and longest (40 mu diameter) were found clustered close to the origin of the axial arteries. The density of the laminar AVAs was estimated to be 500 AVAs/cm2. Blood vessels of the dermal papillae of the periople, coronary band, distal laminae, sole and frog shared a basic structural organisation. The cast of each papillary unit consisted of a central artery and vein enmeshed in a sheath of fine capillaries. At intervals along the length of the central artery were short branches which gave rise to tufts of capillaries. The capillaries formed a tortuous anastomosing plexus which encircled the papillary unit and drained into the central vein at intervals along its length. AVAs were always present at the base of the papillary units and anastomoses connected the central artery and vein. AVAs are important components of the dermal microcirculation of the equine foot and their distribution and density is compatible with their proposed role in the pathophysiology of equine laminitis. PMID- 2318187 TI - Surgical repair of collagenolytic ulcerative keratitis in the horse. PMID- 2318188 TI - Enantiomer resolution in immobilized pH gradient gels via inclusion of a chiral discriminator. AB - The separation of enantiomeric forms of dansylated amino acids by isoelectric focusing in immobilized pH gradients (IPG) is demonstrated for the first time. Separations occur in a pH 3.0-4.0 IPG interval, in presence of 7Murea, 10% methanol and 60 mM beta-cyclodextrin (CD) as chiral discriminator. It is found that the inclusion complex formed between the D-form and CD has a lower pI than the uncomplexed form (delta pI = 0.05 for DL-Phe and delta pI = 0.025 for DL Trp); from this, it is calculated that the pK of the tertiary amino group in the dansyl moiety is lowered by 0.1 pH unit in the former case (D-Phe) and by 0.05 in the case of D-Trp (both values referring to 60 mM CD gels). For some racemates (e.g., DL-Phe) the separation mechanism is still operative with CD concentrations as low as 20 mM. In our system 60 mM CD appears to be the solubility limit of CD. As the complex is stable in the electric field for at least 15 h, this separation mechanism could be exploited for purifying large quantities of pure D and L forms from racemates in multicompartment electrolyzers with isoelectric Immobiline membranes. PMID- 2318189 TI - Reassessment of commercially available molecular weight standards for peptide sodium dodecyl sulfate-polyacrylamide gel electrophoresis using electroblotting and microsequencing. AB - Myoglobin CNBr peptides, constituting the commercially available molecular weight calibration kits for sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were analyzed by microsequencing after electroblotting on polyvinylidene difluoride (Immobilon) membranes. An obvious disagreement was found between peptide identification and the data provided by the manufacturers. We observed 6 peptides from Mr 2500 to 17,000 corresponding, in increasing size order, to the 3 peptides resulting from the total CNBr digestion, to 2 incompletely cleaved peptides and to the intact myoglobin. Using a corrected calibration curve, a linear relationship was established from Mr 6000 to 43,000 and a second one for shorter peptides. This method of electrophoresis and electroblotting, easily adapted for peptides, is a powerful tool for peptide identification correlated with size determination. It is especially useful for CNBr-cleaved peptides. PMID- 2318190 TI - Multiple successive immunoprinting: a fast blotting technique of a single agarose isoelectric focusing gel. AB - Multiple successive pressure blottings of a single agarose isoelectric focusing gel were performed on normal and CNBr-activated nitrocellulose (NC) filters. The results obtained by multiple successive 10s immunoprints were compared to those obtained by a single 10 min immunoprint. To quantify the transfer efficiency of these techniques, a defined amount of radioactive material was separated by isoelectric focusing on agarose gel. After separation and pressure blottings of the gel the NC filters were submitted to autoradiography. The amount of radioactive material bound to the NC filters was determined by scintillation technique. The single 10 min pressure blot was more efficient than each of the multiple successive 10s prints. However, the latter procedure allowed equal resolution and resulted in a higher recovery of total radioactivity than the single immunoprint technique. The aim of this paper is to show how to obtain highly reproducible prints of electrophoretic patterns in an agarose gel of heterogeneous samples when accurate multiple immunodetections are to be performed. This technique was tested to characterize the grass pollen specific immunoglobulin classes and subclasses from an allergic patient. PMID- 2318191 TI - The electric field dependence of DNA mobilities in agarose gels: a reinvestigation. AB - The electric field dependence of the electrophoretic mobility of linear DNA fragments in agarose gels was reinvestigated in order to correct the observed mobilities for the different temperatures actually present in the gel during electrophoresis in different electric field gradients. When corrected to a common temperature, the electrophoretic mobilities of DNA fragments less than or equal to 1 kilobase pairs (kbp) in size were independent of electric field strength at all field strengths from 0.6 to 4.6 V/cm if the gels contained less than or equal to 1.4% agarose. The mobilities of larger DNA fragments increased approximately linearly with electric field strength. If the agarose concentration was higher than 2%, the mobilities of all DNA fragments increased with increasing electric field strength. The electric field dependence of the mobility was larger in gels cast and run in Tris-borate buffer (TBE) than in gels cast and run in Tris acetate buffer (TAE), and was more pronounced in gels without ethidium bromide incorporated in the matrix. Ferguson plots were constructed for the various DNA fragments, both with and without extrapolating the temperature-corrected mobilities to zero electric field strength. Linear Ferguson plots were obtained for all fragments less than or equal to 12 kbp in size in agarose gels less than or equal to 1.4% in concentration if the mobilities were first extrapolated to zero electric field strength. Concave upward curvature of the Ferguson plots was observed for DNA fragments greater than or equal to 2 kbp in size at finite electric field strengths. Convex downward curvature of the Ferguson plots was observed for DNA fragments greater than or equal to 1 kbp in size in agarose gels greater than or equal to 2% in concentration. The mobilities of the various DNA fragments, extrapolated to zero agarose concentration and zero electric field strength, decreased with increasing DNA molecular weight; extrapolating to zero molecular weight gave an "intrinsic" DNA mobility of 2.7 x 10(-4) cm2/Vs at 20 degrees C. The pore sizes of LE agarose gels cast and run in TAE and TBE buffers were estimated from the mobility of the DNA fragments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2318192 TI - Haptoglobin subtype determination by isoelectric focusing in agarose gel: application to paternity testing and presentation of a new alpha 2-variant. AB - Haptoglobin subtyping of a Danish population sample (n = 2184) by a modified isoelectric focusing/immunoblotting method, using agarose gel and visualization by an alkaline phosphatase conjugated antibody, is presented. The allele frequencies were: Hp*1F 0.151; Hp*1S 0.241; Hp*2FS 0.565; Hp*2SS 0.040; Hp*2FF 0.002; Hp J*0.0002. Based on these data the theoretical change of exclusion of nonfathers in paternity cases was calculated to be 35%. Examination of 51 families with 120 children and of 648 mother/child pairs showed no exceptions from Mendelian inheritance. The results obtained by application of Hp subtyping to 405 paternity cases are given and the reliability of the method is discussed. A new alpha 2-variant occurring in the father and in two of three siblings of a Danish family is presented. PMID- 2318193 TI - Two-dimensional polyacrylamide gel electrophoresis of extracellular soybean pathogenesis-related proteins using PhastSystem. AB - Acidic and basic pathogenesis-related proteins (PR-Ps) were extracted from the intercellular fluid (IF) of soybean leaves, locally infected with tobacco necrosis virus and showing necrotic local lesions. Proteins were detected by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) using PhastSystem and precast commercially available gels. Extracts from healthy leaves were run as controls. PR-Ps were first run under native PAGE conditions or isoelectric focusing (IEF), the gels stained with Coomassie Blue, then run under sodium dodecyl sulfate (SDS)-denaturing conditions and finally stained with silver. Ten major acidic PR-Ps were separated; their Mr's were close to those found by conventional PAGE. Their isoelectric points ranged from 3.5 to 5.0. Ten basic PR Ps were separated and their Mr's estimated. None of these acidic or basic soybean PR-Ps was a glycoprotein. PAGE with PhastSystem and precast gels gives reliable results, comparable with those from conventional 2D-PAGE, with simpler experimental procedures. By electrophoresing Coomassie-stained gels with SDS in the second dimension, we were able to control the first-dimensional separation and to avoid laborious protocols generally adopted with unstained gels. PMID- 2318194 TI - Identification and quantification of apolipoprotein D in normal human urine. AB - Apolipoprotein D has been identified in normal human urine, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by immunoblotting with monospecific antibodies. Urinary apolipoprotein D appeared as a main 33,000 u protein together with a minor fraction corresponding to its partially deglycosylated species of lower molecular mass. No high molecular mass forms of apolipoprotein D naturally occurring in plasma could be detected. The apolipoprotein D mean +/- SD concentration assayed with rocket immunoelectrophoresis, in urine samples from nine apparently healthy normal men, was 1.4 +/- 1.0 mg/L (range: 0.2-3.0 mg/L). Among the plasma apolipoproteins, apolipoprotein D behaves uniquely as regards its excretion in urine; the other apolipoproteins belonging to the A, B, D and E groups, although of low molecular masses, are present, at most, in trace amounts in normal urine. PMID- 2318195 TI - Separation of some triazine herbicides and their solvolytic products by capillary zone electrophoresis. AB - The separation of triazine herbicides and their solvolytic products by capillary zone electrophoresis in mixed water-ethanol background electrolytes is described, allowing the analysis of picomole amounts of a triazine mixture in less than 15 min. PMID- 2318196 TI - Metabolic studies with NMR spectroscopy of the alga Dunaliella salina trapped within agarose beads. AB - A technique for the entrapment of the unicellular algae Dunaliella salina in agarose beads and their perfusion during NMR measurements is presented. The trapped cells maintained their ability to proliferate under normal growth conditions, and remained viable and stable under steady-state conditions for long periods during NMR measurements. Following osmotic shock in the dark, prominent changes were observed in the intracellular level of ATP and polyphosphates, but little to no changes in the intracellular pH or orthoposphate content. When cells were subjected to hyperosmotic shock, the ATP level decreased. The content of NMR visible polyphosphates decreased as well, presumably due to the production of longer, NMR-invisible structures. Following hypoosmotic shock, the ATP content increased and longer polyphosphates were broken down to shorter, more mobile polymers. PMID- 2318197 TI - The role of intracellular orthophosphate in triggering osmoregulation in the alga Dunaliella salina. AB - A new hypothesis is presented for the mechanism of metabolic response during osmoregulation in the alga Dunaliella salina. We propose that the osmotic response is initiated by differential volume changes of the cytoplasm and the chloroplast (observed using the electron microscope) which alter the cytoplasmic orthophosphate concentration. This triggers a flow through the Pi/triose phosphate shuttle, activating chloroplast enzymes in the direction of either starch or glycerol synthesis. The Pi-dependent response was investigated in vivo using NMR. The rates of glycerol synthesis or elimination following osmotic shocks were modulated by the intracellular Pi level as predicted by the hypothesis. PMID- 2318198 TI - Mechanism of glucocorticoid regulation of alkaline phosphatase gene expression in osteoblast-like cells. AB - In the rat osteosarcoma cell line ROS 17/2.8, glucocorticoids increase the activity of the plasma membrane enzyme, alkaline phosphatase. To determine the mechanisms responsible for this effect, we have studied the actions of dexamethasone on alkaline phosphatase activity, immunoreactive protein, and steady-state mRNA levels. Dexamethasone treatment increased both specific activity of alkaline phosphatase and the cell surface expression of immunoreactive protein in a dose-dependent manner, with a half-maximal increase at 2 nM. Steady-state alkaline phosphatase mRNA levels were also increased in a dose-dependent manner. The time course of dexamethasone induction occurred relatively slowly, with a lag period of 12 h before any discernable effect on alkaline phosphatase mRNA levels. The rise in alkaline phosphatase mRNA levels was attributable entirely to changes in gene transcription, with no effect on message stability. Treatment of ROS 17/2.8 cells with actinomycin D completely abolished the dexamethasone-induced rise in alkaline phosphatase mRNA levels. Measurement of alkaline phosphatase mRNA degradation, by incubation of cells with the transcriptional inhibitor 5,6-dichloro-ribofuranosylbenzimidazole, indicated an apparent half-life of 24 h in both untreated and dexamethasone-stimulated cells. The protein synthesis inhibitors cycloheximide and puromycin blocked the dexamethasone induction of alkaline phosphatase mRNA. These data suggest that the dexamethasone-induced rise in alkaline phosphatase gene transcription requires the synthesis of an unknown mediator protein. PMID- 2318199 TI - Nuclear magnetic relaxation studies of the role of the metal ion in Mn2(+) substituted aminoacylase I. AB - Substitution of the essential Zn2+ ions of porcine kidney aminoacylase I (EC 3.5.1.14) by Mn2+ did not markedly affect the kinetic properties of the enzyme. Using Mn2+ as a paramagnetic probe, we were able to study the conformations of bound ligands by measuring the enhancement of ligand proton relaxation in 1H NMR. In addition, the effects of inhibitors on the paramagnetic enhancement of water proton relaxation rates were examined. The results of both approaches, in agreement with kinetic evidence, suggest that the metal center of aminoacylase I is too distant from the ligand binding site to allow direct participation of the metal in substrate binding or catalysis. We, therefore, propose that the metal ion of aminoacylase I plays a purely structural role. PMID- 2318200 TI - Differential scanning calorimetry of lobster haemocyanin. AB - Differential scanning calorimetry has been performed with Palinurus vulgaris haemocyanin monomers and hexamers. The denaturation of the protein is irreversible. Both the temperature of the transition maximum and the enthalpy are lower for the monomer than for the hexamer. A scan rate dependence of the temperature of the maxima is found for both the monomer and the hexamer; for the hexamer at least, this can be explained in terms of a two-state kinetic model. Some comments are made as to the use of equilibrium thermodynamics in the analysis of irreversible scanning calorimetric traces. PMID- 2318201 TI - Ontogenesis of rabbit liver cytochrome P450. Evidence for a cytochrome P450-IIE (3a)-related form prevailing during the post-natal period. AB - The liver hydroxylating system, mainly composed of cytochromes P450, is not highly active during foetal life. If develops after birth and reaches the adult level several weeks post-partum. We have studied the ontogenesis of rabbit cytochrome P450 during the post-natal period. Total P450 as well as isozymes 2, 3b, 3c, 4 and 6 were measured. The evolution of these proteins with ageing, together with qualitative modification of an electrophoretic profile, produced evidence of an early developing P450 prevailing from one week to three weeks after birth. We isolated and characterized a cytochrome, called P450 2y, from two week liver microsomes. It is closely related to P450 3a, an adult form of rabbit P450 induced by ethanol. They have similar molecular masses, the same lambda max of CO-reduced spectrum and exhibit immunological cross-reactivity. However, we cannot conclude that the two proteins are identical from N-terminal amino acid analysis or the two-dimensional gel electrophoresis pattern. These results, as well as the recent evidence of two different genes coding for the P450 3a family, strengthen the idea that P450 2y and 3a are distinct proteins. P450 2y seems to be an early developing form abundant soon after birth, while P450 3a is a delayed form appearing like most P450 isozymes during the fourth post-natal week. Besides the quantitative development during perinatal life, there is an important qualitative modification of liver cytochrome P450 content. PMID- 2318202 TI - Lactate dehydrogenase from the extreme thermophile Thermotoga maritima. AB - Lactate dehydrogenase was isolated from the extreme thermophilic eubacterium Thermotoga maritima. The enzyme is stereospecific for L(+)-lactate. It represents a homotetramer of 144 kDa molecular mass, with a sedimentation coefficient of s20,w approximately 7 S. Under physiological temperature conditions, the enzyme shows high catalytic efficiency with a broad pH optimum at pH 7.0 +/- 1.0, and long-term stability up to 80 degrees C. The coenzyme, NAD+, and the effector fructose 1,6-bisphosphate [Fru(1,6)P2] increase the thermal stability: at 90 degrees C (pH 6.0), the liganded enzyme exhibits a half-life of thermal inactivation of 150 min. The enhanced rigidity of the enzyme at ambient temperature is reflected by an anomalously high stability toward guanidine denaturation: the midpoint of the equilibrium transition being 1.6 M guanidine hydrochloride. Under optimum conditions of the enzyme assay, the Michaelis constants (Km) for NADH, NAD+, pyruvate and L(+)-lactate at 55 degrees C, and in the absence of Fru(1,6)P2, are 0.03 mM, 0.09 mM, 3.7 mM and 410 mM, respectively; Fru(1,6)P2 as a positive effector shifts the Km values for pyruvate and L(+) lactate to 0.06 mM and 25 mM, respectively. The Km values for the coenzyme are not affected. Neither Mn2+ nor other divalent cations have any activating effect. In contrast to lactate dehydrogenases from eukaryotes, the N-terminus of the enzyme from Th. maritima is not acetylated. Comparison of the 30 N-terminal amino acid residues with lactate dehydrogenase from Thermus aquaticus shows a high degree of similarity. This also holds if the two lactate dehydrogenases are compared with the glyceraldehyde-3-phosphate dehydrogenases from the same organisms. PMID- 2318203 TI - A structure-reactivity study of the binding of acetylglutamate to carbamoyl phosphate synthetase I. AB - The requirements for binding at the N-acetyl-L-glutamate binding site of carbamoyl phosphate synthetase I were studied by the displacement of the activator from the central enzyme complex by analogs. Two carboxyls are essential and the acetamido group, if linked to the alpha-carbon, enhances binding 5000 fold. The subsite for the delta-carboxyl is mobile with respect to that for the alpha-carboxyl. Mixtures of complementary fragment of acetylglutamate do not bind, indicating a strong 'chelate' effect. Substituents revealed the existence of steric constraints around the delta-carboxyl, the alpha and gamma-carbons, and the whole of the acetamido group. However, phenyl substituents at the beta-carbon did not hamper binding, indicating that substituents at the beta-carbon face the solution. This is consistent with binding of acetylglutamate as the minimum energy conformer. All analogs binding with high affinity are activators. Some analogs that bind poorly are competitive inhibitors. They appear to bind preferentially to a low-affinity conformation adopted by the site when the products dissociate and the substrates bind. The acetamido group plays no role in the binding of the inhibitors but it is crucial for the binding of the activators, and the high- and low-affinity conformations of the site differ markedly in structural selectivity. PMID- 2318204 TI - Chemical characterization of the regularly arranged surface layer glycoprotein of Clostridium thermosaccharolyticum D120-70. AB - Clostridium thermosaccharolyticum D120-70 possesses as its outermost cell envelope layer a square-arranged array of glycoprotein molecules. SDS/polyacrylamide gel electrophoresis of the purified surface layer showed a broadened band in the molecular mass range of about 115 kDa which, upon periodic acid/Schiff staining, gave a positive reaction. After proteolytic degradation of this material, two glycopeptide fractions were obtained. One- and two-dimensional nuclear magnetic resonance studies, together with methylation analysis and periodate oxidation, were used to determine the structures of the polysaccharide portions of these glycopeptides. The combined chemical and spectroscopic evidence suggests the following structures: (formula; see text). PMID- 2318205 TI - Infrared spectroscopic studies of detergent-solubilized uncoupling protein from brown-adipose-tissue mitochondria. AB - The uncoupling protein of brown-adipose-tissue mitochondria has been purified in the form of mixed micelles with lipid and reduced Triton X-100. This surfactant has the advantage over conventional Triton X-100, that it does not interfere with amide bands in infrared spectra. The structure of the uncoupling protein in micellar form has been examined by Fourier-transform infrared spectroscopy (FTIR). In order to decompose the amide I contour into its components, band narrowing (Fourier derivation and deconvolution) and band-decomposition techniques have been used. Combining data from spectra taken in H2O and 2H2O media, the following percentage distribution of secondary structure patterns has been obtained: 50% alpha-helix, 28-30% beta-structure; 13-15% beta-turns and 7% unordered. Thermal denaturation of the uncoupling protein has also been monitored by FTIR. In accordance with previous observations of different proteins, thermal denaturation is marked by a shift in the amide I maximum and the appearance of two new peaks in 2H2O, at around 1620 cm-1 and 1685 cm-1. Denaturation occurs in the 40-50 degrees C temperature range, in agreement with studies of GDP-binding capacity. Cooling down the thermally denatured protein produces a new change in its secondary structure; however, the original conformation is not restored. The uncoupling protein possesses a nucleotide-binding site. On addition of GDP, small changes in protein conformation occur, attributable to changes in tertiary structure. However, no detectable effects are seen in the presence or absence of the other physiological regulators, the free fatty acids. The uncoupling protein shares important similarities in its primary structure with other anion carriers of the mitochondrial membrane; one of these, the adenine-nucleotide translocator, has been used in a comparative study, applying the same FTIR techniques described above for the uncoupling protein. Both proteins have a similar proportion of alpha-helix, probably corresponding to the segments spanning the membrane, but the conformation of the polar domains appears to differ. PMID- 2318206 TI - Mapping of glucose and glucose-6-phosphate binding sites on bovine brain hexokinase. A 1H- and 31P-NMR investigation. AB - Inhibition of bovine brain hexokinase by its product, glucose 6-phosphate, is considered to be a major regulatory step in controlling the glycolytic flux in the brain. Investigations on the molecular basis of this regulation, i.e. allosteric or product inhibition, have led to various proposals. Here, we attempt to resolve this issue by ascertaining the location of the binding sites for glucose and glucose 6-phosphate on the enzyme with respect to a divalent-cation binding site characterized previously [Jarori, G. K., Kasturi, S. R. & Kenkare, U. W. (1981) Arch. Biochem. Biophys. 211, 258-268]. The paramagnetic effect of enzyme-bound Mn(II) on the spin-lattice relaxation rates (T-1(1] of ligand nuclei (1H and 31P) in E.Mn(II).Glc and E.Mn(II).Glc6P complexes have been measured. The paramagnetic effect of Mn(II) on the proton relaxation rates of C1-H alpha, C1-H beta and C2-H beta of glucose in the E.Mn(II).Glc complex was measured at 270 MHz and 500 MHz. The temperature dependence of these rates was also studied in the range of 5-30 degrees C at 500 MHz. The ligand nuclear relaxation rates in E.Mn(II).Glc are field-dependent and the Arrhenius plot yields an activation energy (delta E) of 16.7-20.9 kJ/mol. Similar measurements have also been carried out on C1-H alpha, C1-H beta and C6-31P at 270 MHz (1H) and 202.5 MHz (31P) for the E.Mn(II).Glc6P complex. The temperature dependence of 31P relaxation rates in this complex was measured in the range 5-30 degrees C, which yielded delta E = 9.2 kJ/mol. The electron-nuclear dipolar correlation time (tau c), determined from the field-dependent measurements of proton relaxation rates in the E.Mn(II).Glc complex, is 0.22-1.27 ns. The distances determined between Mn(II) and C1-H of glucose and glucose 6-phosphate are approximately 1.1 nm and approximately 0.8 nm, respectively. These data, considered together with our recent results [Mehta, A., Jarori, G. K. & Kenkare, U. W. (1988) J. Biol. Chem. 263, 15492-15498], suggest that glucose and glucose 6-phosphate may bind to very nearly the same region of the enzyme. The structure of the binary Glc6P.Mn(II) complex has also been determined. The phosphoryl group of the sugar phosphate forms a first co-ordination complex with the cation. However, on the enzyme, the phosphoryl group is located at a distance of approximately 0.5-0.6 nm from the cation. PMID- 2318207 TI - Evidence for a specific mechanism of laminin assembly. AB - The specificity of laminin chain assembly was investigated using fragments E8 and C8-9, derived from the long arm of the molecule, whose rod-like domain consists of the alpha-helical regions of the A, B1 and B2 chains. Urea-induced chain separation and unfolding were monitored by transverse urea/polyacrylamide gel electrophoresis (PAGE) and circular dichroism. Separation of the A and disulphide linked B1-B2 chains occurred at 3.5-4.0 M urea and by 7.0 M urea all residual alpha-helicity was lost. Removal of urea by dialysis resulted in high recoveries (87-100%) of renatured protein which in its apparent molecular mass, alpha-helix content, chain composition, degree of association and ultrastructural appearance was indistinguishable from native E8. Reduction or reduction and alkylation of the chains did not lead to a decrease in their ability to reassemble specifically. Reformation of the single interchain disulphide, linking the B1 and B2 chains, clearly demonstrates that these chains are correctly aligned in parallel and in register in E8 renatured from its reduced chains. Renaturation of E8 from its reduced and alkylated chains precludes a role for disulphide formation in determining chain alignment but suggests rather than it is involved in the stabilisation of the correctly assembled molecule. These results, together with recent sequence data, provide evidence for the interaction of the alpha helical regions of the A, B1 and B2 chains in the formation of a triple coiled coil within the long arm of the molecule. The highly specific nature of this interaction suggests that it is the mechanism by which laminin is assembled in vivo. PMID- 2318208 TI - Interaction of upstream stimulatory factor with the human heme oxygenase gene promoter. AB - Upstream stimulatory factor (USF), originally identified in HeLa cells, interacts with the upstream promoter sequence of adenovirus 2 major late promoter (Ad2MLP) and activates its transcription. USF is present in uninfected HeLa cells and appears to be involved in the transcription of cellular genes related to stress. Recently, we have proposed that the rat heme oxygenase gene, newly identified heat-shock protein gene, is regulated at least in partly by a rat homolog of USF [Sato, M., Fukushi, Y., Ishizawa, S., Okinaga, S., Muller, R.M. & Shibahara, S. (1989) J. Biol. Chem. 264, 10251-10260]. We therefore confirm that the heme oxygenase gene is expressed in HeLa cells and its expression is increased by cadmium, suggesting that human heme oxygenase is a stress protein similar to the metallothioneins. Using partially purified USF from HeLa cells, we show that USF binds to the human heme oxygenase gene promoter and stimulates its cell-free transcription. The cis-acting element, identified as CACGTGACCCG, is located 34 bp upstream from the transcription initiation site, and contains the core sequence of the upstream promoter sequence of Ad2MLP. We propose that USF contributes to the transcription of the human heme oxygenase gene. PMID- 2318209 TI - Fast and slow isoforms of troponin I and troponin C. Distribution in normal rabbit muscles and effects of chronic stimulation. AB - Polyclonal antibodies were raised against troponin I (TnI) and troponin C (TnC) purified from fast-twitch and slow-twitch rabbit muscles. These antibodies were used to elucidate the distribution of fast and slow isoforms of TnI and TnC in normal and chronically stimulated rabbit hind limb muscles by immunoblots of one dimensional and two-dimensional electrophoreses. In contrast to the multiplicity of fast and slow troponin T (TnT) isoforms, TnI and TnC were present as unique fast and slow isoforms. Whereas no charge variants were detected for slow TnI, fast TnI was present in at least three charge variants. As judged from the results of alkaline phosphatase digestion, these charge variants represent differently phosphorylated forms. Fast and slow TnC both exist as two charge variants which, however, were unaffected by alkaline phosphatase treatment. Chronic low-frequency stimulation of fast-twitch muscles induced progressive increases in the slow isoforms of TnC and TnI at the expense of their fast isoforms. The extent of the fast-to-slow transition was more pronounced in the case of TnC than in that of TnI. Long-term stimulated muscles with a complete fast-to-slow transition, at the level of the TnT isoforms, still contained fast and slow isoforms of both TnI and TnC. The coexistence of fast and slow isoforms of the three troponin subunits in the transforming muscle was interpreted as indicating the presence of hybrid troponin molecules composed of fast and slow isoforms. Studies at the mRNA level showed changes similar to those at the protein level. However, in long-term stimulated muscles, the fast-to-slow transition of TnI was more pronounced at the mRNA level than at the protein level. PMID- 2318210 TI - Characterization of a soluble form of human CD4. Peptide analyses confirm the expected amino acid sequence, identify glycosylation sites and demonstrate the presence of three disulfide bonds. AB - CD4 is a glycoprotein that is expressed on the surface of a variety of cells of the immune system and is believed to participate in the interactions of these cells with antigen-presenting cells bearing the class II major histocompatibility (MHC) antigens. CD4 also acts as the receptor for the human immunodeficiency virus (HIV) by binding to the viral glycoprotein gp120. Recombinant soluble CD4 (rCD4) is a truncated form of human CD4 that is secreted from transfected Chinese hamster ovary cells. This 368-amino-acid glycoprotein contains two potential sites of N-linked glycosylation (Asn-271 and Asn-300) and six cysteine residues. Amino-terminal sequence analysis demonstrated that the sequence begins at the third residue of the polypeptide originally predicted from the cDNA analysis [Maddon, P.J. et al. (1985) Cell 42, 93-104]. The rest of the primary sequence was confirmed by analysis of peptides purified by reversed-phase HPLC after digestion of S-carboxymethylated rCD4 with trypsin. Anhydrotrypsin affinity chromatography of trypsin-digested rCD4 confirmed that the carboxy-terminus of the protein was Pro-368. Enzymatic digestion of non-reduced rCD4 generated disulfide-bonded fragments that demonstrated the presence of disulfide bonds between Cys-16 and Cys-84, Cys-130 and Cys-159, and between Cys-303 and Cys-345. The constituent monosaccharides of the carbohydrate structures of rCD4 were found to be fucose, mannose, galactose, N-acetylglucosamine and N-acetylneuraminic acid. Characterization of the tryptic map of rCD4 after treatment with peptide: N glycosidase F demonstrated that both potential N-glycosylation sites are utilized. The tryptic map of rCD4 treated with endo-beta-N-acetylglucosamine H demonstrated that only complex-type oligosaccharides are attached to Asn-271, while Asn-300 has high-mannose or hybrid structures attached in addition to complex-type oligosaccharides. Glucosamine was observed only in glycopeptides that contain Asn-300 or Asn-271 while no galactosamine was observed. This suggests that rCD4 contains no O-linked oligosaccharides. PMID- 2318211 TI - Topological analysis of hydrogen bonding in protein structure. AB - A recent study has shown that topological stereoisomers exist for the polypeptide chain in disulfide-containing proteins that are represented by non-planar graphs. This topological stereochemistry is demonstrated in the structure of variant 3 toxin in the venom of the North American scorpion Centruroides sculpturatus Ewing and the structure of toxin II from the North African scorpion Androctonus australis Hector. In this report, we found that a similar topological analysis can be applied to the hydrogen bonding in alpha-helices and beta-sheets within protein molecules, and we described the topological characteristics of chiral properties of protein secondary structure elements. Specifically, a closed right handed alpha-helix of more than six residues long is shown formally to be non planar and has the L topology. Antiparallel beta-sheets are planar. Two parallel beta-strands each of at least three residues in length, however, constitute a non planar structural element and can have either L or D topology. The favored right handed crossover for parallel beta-sheets has the L form, the same as the right handed alpha-helix. This topological description of the hydrogen bonding in secondary structures may be extended to higher levels of protein structure and may provide a conceptual framework for studying complex protein architecture in general. PMID- 2318212 TI - Distance between the substrate and regulatory reduced coenzyme binding sites of bovine liver glutamate dehydrogenase by resonance energy transfer. AB - Bovine liver glutamate dehydrogenase is known to bind reduced coenzyme at two sites/subunit, one catalytic and one regulatory; ADP competes for the latter site. The enzyme is here shown to be catalytically active with the thionicotinamide analogue of NADPH [( S]NADPH). For native enzyme, ultrafiltration studies revealed that [S]NADPH reversibly occupies about two sites/enzyme subunit in the absence of other ligands; by the addition of ADP, [S]NADPH binding can be limited to one molecule/subunit. The enzyme is irreversibly inactivated by reaction with 4-(iodoacetamido)salicylic acid (ISA) at lysine126 within the 2-oxoglutarate binding site [Holbrook, J.J., Roberts, P.A. & Wallis, R.B. (1973) Biochem. J. 133, 165-171]. ISA-modified enzyme binds 1 molecule [S]NADPH/subunit in the absence of ADP, suggesting that reaction at the substrate site blocks binding at the catalytic, but not at the regulatory site. The fluorescence spectrum of ISA-modified enzyme overlaps the absorption spectrum of [S]NADPH allowing a distance measurement between these sites by resonance energy transfer. [S]NADPH quenches the emission of ISA-modified enzyme, yielding 3.2 nm as the average distance between sites. ADP competes for the [S]NADPH site but does not affect the fluorescence of ISA-modified enzyme, indicating that [S]NADPH quenching is attributable to energy transfer rather than to a conformational change. The 3.2 nm thus represents the distance between the 2 oxoglutarate and reduced coenzyme regulatory sites of glutamate dehydrogenase. PMID- 2318213 TI - Modified branched-chain amino acid pathways give rise to acyl acids of sucrose esters exuded from tobacco leaf trichomes. AB - A major diversion of carbon from branched-chain amino acid biosynthesis/catabolism to form acyl moieties of sucrose esters (6-O-acetyl-2,3,4 tri-O-acyl-alpha-D-glucopyranosyl-beta-D- fructofuranosides) was observed to be associated with specialized trichome head cells which secrete large amounts of sucrose esters. Surface chemistry and acetyl and acyl substituent groups of tobacco (T.I. 1068) sucrose esters were identified and quantified by gas chromatography/mass spectrometry. Sucrose esters were prominent surface constituents and 3-methylvaleric acid, 2- and 3-methylbutyric acid, and methylpropionic acid accounted for 60%, 25% and 9%, respectively, of total C3--C7 acyl substituents. Radiolabeled Thr, Ile, Val, Leu, pyruvate and Asp, metabolites of branched-chain amino acid pathways, were compared with radioactively labeled acetate and sucrose as donors of carbon to sucrose, acetyl and acyl components of sucrose esters using epidermal peels with undisturbed trichomes. Preparations of biosynthetically competent trichome heads (site of sucrose ester formation) were also examined. Results indicate that 3-methylvaleryl and 2-methylbutyryl groups are derived from the Thr pathway of branched-chain amino acid metabolism, 3 methylbutyryl and methylpropionyl groups are formed via the pyruvate pathway, and that acetyl groups are principally formed directly via acetyl-CoA. Arguments are presented which rule out participation of fatty acid synthase in the formation of prominent acyl acids. Results suggest that the shunting of carbon away from the biosynthesis of Val, Leu and Ile may be due to a low level of amino acid utilization in protein synthesis in specialized glandular head cells of trichomes. This would result in the availability of corresponding oxo acids for CoA activation and esterification to form sucrose esters. Preliminary evidence was found for the involvement of cycling reactions in oxo-acid-chain lengthening and for utilization of pyruvate-derived 2-oxobutyrate to form straight-chain acyl substituents. PMID- 2318214 TI - Glucose requirement for postischemic recovery of perfused working heart. AB - The quantitative importance of glycolysis in cardiomyocyte reenergization and contractile recovery was examined in postischemic, preload-controlled, isolated working guinea pig hearts. A 25-min global but low-flow ischemia with concurrent norepinephrine infusion to exhaust cellular glycogen stores was followed by a 15 min reperfusion. With 5 mM pyruvate as sole reperfusion substrate, severe contractile failure developed despite normal sarcolemmal pyruvate transport rate and high intracellular pyruvate concentrations near 2 mM. Reperfusion dysfunction was characterized by a low cytosolic phosphorylation potential [( ATP]/[( ADP][Pi]) due to accumulations of inorganic phosphate (Pi) and lactate. In contrast, with 5 mM glucose plus pyruvate as substrates, but not with glucose as sole substrate, reperfusion phosphorylation potential and function recovered to near normal. During the critical ischemia-reperfusion transition at 30 s reperfusion the cytosolic creatine kinase appeared displaced from equilibrium, regardless of the substrate supply. When under these conditions glucose and pyruvate were coinfused, glycolytic flux was near maximum, the glyceraldehyde-3 phosphate dehydrogenase/3-phosphoglycerate kinase reaction was enhanced, accumulation of Pi was attenuated, ATP content was slightly increased, and adenosine release was low. Thus, glucose prevented deterioration of the phosphorylation potential to levels incompatible with reperfusion recovery. Immediate energetic support due to maximum glycolytic ATP production and enhancement of the glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase reaction appeared to act in concert to prevent detrimental collapse of [ATP]/[( ADP][Pi]) during creatine kinase dysfunction in the ischemia-reperfusion transition. Dichloroacetate (2 mM) plus glucose stimulated glycolysis but failed fully to reenergize the reperfused heart; conversely, 10 mM 2-deoxyglucose plus pyruvate inhibited glycolysis and produced virtually instantaneous de energization during reperfusion. The following conclusions were reached. (1) A functional glycolysis is required to prevent energetic and contractile collapse of the low-flow ischemic or reperfused heart (2). Glucose stabilization of energetics in pyruvate-perfused hearts is due in part to intensification of glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase activity. (3) 2-Deoxyglucose depletes the glyceraldehyde-3-phosphate pool and effects intracellular phosphate fixation in the form of 2-deoxyglucose 6-phosphate, but the cytosolic phosphorylation potential is not increased and reperfusion failure occurs instantly. (4) Consistent correlations exist between cytosolic ATP phosphorylation potential and reperfusion contractile function. The findings depict glycolysis as a highly adaptive emergency mechanism which can prevent deleterious myocyte deenergization during forced ischemia-reperfusion transitions in presence of excess oxidative substrate. PMID- 2318215 TI - Enterococcal resistance to vancomycin and related cyclic glycopeptide antibiotics. AB - Enterococci belonging to various species resistant to vancomycin and related cyclic glycopeptide antibiotics have been isolated from hospitalized patients in France, the UK and the USA. All such strains examined display inducible synthesis of a membrane protein associated with resistance. The mechanism by which the membrane protein acts has not been definitively established, but it may block the access of the antibiotic to its peptidoglycan target. That the protein could be a bypass enzyme has not been ruled out. Transfer of glycopeptide resistance by conjugation to either Enterococcus faecium or Enterococcus faecalis and by transformation of Streptococcus sanguis Challis has been reported. The structural and regulatory genes encoding this resistance can be localized on plasmid and, apparently, chromosomal DNA. The plasmids encoding this resistance appear to differ from each other and have variable host ranges, but share at least some DNA sequence homology. PMID- 2318216 TI - Vancomycin-aminoglycoside combinations in therapy of endocarditis caused by Enterococcus species and Streptococcus bovis. AB - Between 1974 and 1986, five patients with enterococcal endocarditis (three of whom had a prosthetic valve) and three patients with Streptococcus bovis endocarditis were treated with a combination of vancomycin and an aminoglycoside for a mean duration of 40 days. This regimen was prescribed because of allergy to beta-lactam (n = 7) and/or failure of previous treatment (n = 4). Three of the eight patients underwent valve replacement. In the six evaluable patients cure was achieved with the vancomycin-aminoglycoside combination. An increase of the creatinine serum levels was observed in all cases but it was never necessary to discontinue treatment, adjustment of the vancomycin and aminoglycoside dosage according to the serum and/or serum creatinine levels allowing continuation of therapy. PMID- 2318217 TI - Comparison of four methods for testing high-level aminoglycoside resistance in enterococci. AB - In a prospective study the prevalence of high-level aminoglycoside resistance (MIC greater than or equal to 2,000 micrograms/ml) among 62 clinically significant enterococci was investigated. A total of 10(5) organisms were inoculated a) onto a plate containing 2,000 micrograms/ml of gentamicin or streptomycin; b) into a microtube for dilution MIC determinations for gentamicin, amikacin, tobramycin and streptomycin; and c) into a single tube containing 500 micrograms/ml of gentamicin, amikacin, tobramycin or streptomycin in supplemented Mueller-Hinton broth. In addition, tubes containing 500 micrograms/ml of gentamicin, amikacin, tobramycin or streptomycin were inoculated with five enterococcal colonies ("crude" method). For 45 of the 62 isolates, MICs of gentamicin, amikacin and tobramycin were less than or equal to 500 micrograms/ml, while 17 (27%) showed high-level resistance. The MICs of streptomycin were less than or equal to 500 micrograms/ml for 42 of 62 isolates, and greater than or equal to 2,000 micrograms/ml for 20 (32.3%). For 8 of the 17 (47%) isolates showing high-level gentamicin resistance, MICs of streptomycin were less than or equal to 500 micrograms/ml. There was complete agreement between the results of the plate method, the microtube dilution MIC and the tube inoculated with 10(5) CFU, but the crude method gave discordant results for two isolates. It is concluded that a tube containing 500 micrograms/ml of aminoglycoside is a simple, accurate and inexpensive method for determining high-level aminoglycoside resistance. PMID- 2318218 TI - Possible evidence of invasiveness of Helicobacter (Campylobacter) pylori. AB - Gastric/duodenal biopsy material from 52 patients was examined immunohistochemically for Helicobacter (Campylobacter) pylori. Specimens from 34 of the patients harboured Helicobacter pylori along the mucosal surface and 13 of these featured, in addition, immunopositive material within the lamina propria. The remaining 18 biopsies were non-reactive. This observation suggests that Helicobacter pylori can penetrate the epithelium and its basement membrane, resulting in the production of specific systemic antibodies. PMID- 2318220 TI - Asymptomatic Yersinia enterocolitica infections during an outbreak in a day nursery. PMID- 2318219 TI - Campylobacter jejuni infection occurring during pregnancy. AB - Campylobacter infections occurring during pregnancy have been associated with spontaneous abortion, stillbirth, prematurity and neonatal sepsis, all ten Campylobacter jejuni infections diagnosed in the approximately 24,000 pregnant women attending a 520-bed hospital between January 1984 and December 1988 were reviewed. Nine women delivered healthy babies at term. In one case, Campylobacter infection at 28 weeks of gestation was associated with premature labour and delivery with subsequent neonatal sepsis and death. One other infant developed Campylobacter jejuni enterocolitis at 3 days of age. Although maternal Campylobacter jejuni infection tends to be mild and self-limited, there may be more serious complications for the fetus or neonate, especially if infection occurs before the third trimester of pregnancy. PMID- 2318221 TI - Absence of relationship between Toxoplasma gondii antibodies and blood group in pregnant women in France. PMID- 2318222 TI - Different results in cardiopulmonary exercise tests after long-term treatment with felodipine and enalapril in patients with congestive heart failure due to ischaemic heart disease. AB - We evaluated the cardiopulmonary exercise test results before and after long-term (16 weeks) treatment with the dihydropyridine calcium antagonist, felodipine (10 mg b.i.d., n = 9), and the ACE inhibitor, enalapril (10 mg b.i.d., n = 11), in 20 patients with New York Heart Association class III congestive heart failure. There were no significant differences at baseline. After 16 weeks patients in the enalapril group showed a significant increase in exercise duration and VO2max, without changes in arterial pressures and heart rate. In the felodipine group, exercise duration and VO2max did not change significantly, but arterial pressures and heart rate were significantly reduced at all exercise levels. Between group analysis showed a significant reduction in arterial pressures and heart rate in the felodipine group compared with enalapril, but no differences in aerobic capacity and exercise duration. These results demonstrate that felodipine and enalapril have essentially different effects on cardiopulmonary exercise results in patients with congestive heart failure. PMID- 2318223 TI - Therapeutic value of a cardioprotective agent in patients with severe ischaemic cardiomyopathy. AB - Trimetazidine (TMZ) has been shown to have anti-ischaemic properties improving exercise tolerance without haemodynamic effects. A 6-month double-blind placebo controlled study was carried out in 20 patients, mean age 59 +/- 6 years, to examine the benefit of adding 60 mg of TMZ vs placebo to the classical therapy, excluding those previously treated with calcium-antagonists, conversion enzyme inhibitors, vasodilators and antiplatelet agents. All patients had severe ischaemic cardiomyopathy, confirmed by coronary angiography; six were in NYHA class IV; 14 in NYHA class III; four had mild recurrent angina pectoris. assessment included clinical and biological evaluation, electrocardiography (ECG), 24-h ECG monitoring, cardiac volume evaluation with chest X-ray, left ventricular fractional shortening by echocardiography, left ventricular ejection fraction by radionuclide angiography. Baseline characteristics were similar in placebo (11 patients) and TMZ (nine patients) groups. Eighteen patients (nine in each group) were followed up for 6 months. In eight patients of the placebo group, treatment had to be modified (addition of calcium antagonists: four patients, conversion enzyme inhibitors: two patients; digitalics: one patient; diuretics: one patient). In the TMZ group, digitalic therapy was withdrawn in one patient and added in one patient (P less than 0.01). At 6 months, all TMZ group patients were free from angina; dyspnoea was improved in all TMZ patients and in only one placebo patient (P less than 0.001). Ejection fraction, increased by 9.3% in the TMZ group and decreased by 15.6% in the placebo group (P less than 0.018), CV decreased by 7% with TMZ, increased by 4% with placebo. (P = 0.034).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318224 TI - Myocardial perfusion after aortic implantation for anomalous origin of the left coronary artery from the pulmonary artery. AB - Postoperative myocardial perfusion and function were evaluated using thallium-201 myocardial imaging and technetium-99m cardiac pool imaging in five patients with an anomalous left coronary artery arising from the pulmonary artery. The patients underwent reimplantation of the left coronary artery at an age ranging from 10 months to 13 years. Postoperative electrocardiographic and radionuclide studies were performed both at rest and during stress 1 to 4 years after the operation. Electrocardiograms which were abnormal preoperatively returned to normal after surgery except that the T wave in lead aVL remained negative. Postoperatively, left ventricular ejection fraction measured by technetium-99m cardiac pool imaging was normal in all patients. Postoperative thallium-201 myocardial imaging, however, showed a perfusion defect with incomplete redistribution at the high-lateral or antero-lateral segment in all patients after a stress test. These data suggest that although myocardial ischaemic change decreases and global cardiac function improves after establishment of a dual coronary artery system, severe myocardial damage remains at the high-lateral or antero-lateral segment. PMID- 2318225 TI - Haemodynamics of induced atrial fibrillation: a comparative assessment with sinus rhythm, atrial and ventricular pacing. AB - The haemodynamics and myocardial lactate consumption during induced atrial fibrillation (AF) were studied in 10 patients with paroxysmal AF. Their mean age (+/- SD) was 61 +/- 5 years and none had clinical evidence of ischaemic or rheumatic heart disease. Compared with sinus rhythm, the onset of AF was associated with a reduction in systolic blood pressure (152 +/- 13 mmHg) in AF vs 169 +/- 23 mmHg in sinus rhythm, P less than 0.01). There was no consistent change in cardiac output at the onset of AF compared with sinus rhythm, but the cardiac output was lower compared with regular atrial pacing at rates similar to those of induced AF (3.85 +/- 0.76 vs 4.38 +/- 0.89 l min-1, P less than 0.02). Compared with sinus rhythm or rate-matched atrial pacing, AF was associated with an elevated pulmonary arterial pressure (24.2 +/- 5.6 mmHg in AF vs 17.9 +/- 14.4 mmHg in sinus rhythm, P less than 0.01) and pulmonary arterial wedge pressure (18.6 +/- 5.6 vs 9.7 +/- 3.9 mmHg, P less than 0.01). The haemodynamic changes during AF were similar to those seen during regular ventricular pacing at an equivalent rate, although the latter was associated with a lower systolic blood pressure (152 +/- 13 mmHg in AF vs 136 +/- 25 mmHg in ventricular pacing, P less than 0.05) and higher right atrial pressure (8.2 +/- 4.4 vs 11.5 +/- 7.5 mmHg respectively, P less than 0.05), presumably due to the deleterious effects of cannon 'a' waves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318226 TI - Exercise-induced sustained symptomatic ventricular tachycardia: incidence, clinical, angiographic and electrophysiologic characteristics. AB - Among 112 patients with sustained ventricular tachycardia, 15 were found to have exercise-induced symptomatic ventricular tachycardia. This population was divided into two subgroups: group 1A included five patients with coronary artery disease and group 1B consisted of 10 patients with no structural heart disease. All patients underwent clinical examination, exercise electrocardiography, left ventriculography, coronary angiography (n = 14) and electrophysiologic study. In group 1B, right ventriculography (n = 7), M mode and two-dimensional echocardiography were also obtained. Group 1A patients were compared with a population of 27 patients with coronary artery disease and chronic sustained ventricular tachycardia not related to exercise (group 2). There were no statistically significant differences between group 1A and group 2 in terms of age, sex, incidence of prior myocardial infarction, NYHA functional class, angina pectoris, symptoms during arrhythmia, severity and extent of coronary arterial lesions, ventricular dysfunction and wall motion abnormalities. In group 1B, coronary angiography and right and left ventricular function were normal. During electrophysiologic study, ventricular tachycardia was initiated in four group 1A patients. In group 1B, ventricular tachycardia was initiated in eight patients. In four of these patients ventricular pacing had to be combined with isoproterenol administration. In group 2, ventricular tachycardia was induced in 26/27 patients. From this study we conclude that in patients with coronary artery disease the electrophysiologic substrate of exercise-related sustained ventricular tachycardia does not differ from the substrate of non-exercise related ventricular tachycardia. Re-entry is the most likely electrophysiologic mechanism. In patients without structural heart disease, the mechanism of the arrhythmia remains speculative. PMID- 2318227 TI - Hypertrophic cardiomyopathy: is a left ventricular outflow tract gradient a major prognostic determinant? AB - The relationship of left ventricular outflow tract gradient as well as of clinical, ECG and haemodynamic data to presenting features and prognosis was evaluated in 125 consecutive patients with hypertropic cardiomyopathy, 79 men and 46 women (mean age: 34 +/- 7 years) studied between January 1970 and December 1985. Most clinical, ECG and haemodynamic findings were similar in the 44 patients (35%) with a pressure gradient (greater than or equal to 30 mmHg) and in the 81 patients (65%) without. Those with obstruction had greater ECG voltage SV1 and RV5; however, higher grade ventricular arrhythmias were more common in patients without obstruction. During a mean follow-up period of 7.6 +/- 4.5 years (range 2-18 years), death from a cardiac cause occurred in 28 patients (21 died suddenly) and was significantly less common in patients with a pressure gradient than in those without (11% vs 28%, P = 0.039). Univariate analysis of survival curves showed that the most powerful predictors of a poor prognosis were ejection fraction P = 0.0001), mean pulmonary artery pressure (P = 0.0001), dyspnoea (P = 0.001), left ventricular end-diastolic pressure (P = 0.002), complex ventricular arrhythmias (P = 0.029) and severe mitral regurgitation (P = 0.037). Using multivariate analysis, a decreased ejection fraction (P = 0.006) and a raised mean pulmonary artery pressure (P = 0.022) were the only independent prognostic determinants. Thus, the presence of a left ventricular outflow tract gradient does not seem of adverse prognostic significance. Risk factor characterization in patients with hypertrophic cardiomyopathy may be improved by assessment of ventricular arrhythmias in the context of left ventricular function. PMID- 2318228 TI - Sensitivity and specificity of dobutamine--electrocardiography test to detect multivessel disease after acute myocardial infarction. AB - The value of dobutamine-electrocardiography (ECG) as a stress test to detect multivessel coronary disease after non-complicated acute myocardial infarction (AMI) was assessed in 75 patients before hospital discharge. Dobutamine-ECG test (dose of 5, 10, 15 and 20 micrograms kg-1 min-1 every 5 min) was performed 5 to 12 days after the beginning of the symptoms of AMI, and coronary angiography within the first month. Heart rate increased from 71 +/- 12 to 106 +/- 17 beats min-1, and systolic blood pressure from 111 +/- 15 to 139 +/- 20 mmHg. Dobutamine test was negative (neither anginal pain, nor ST-segment depression) in 33 patients and positive in 42. The angiographic study showed the presence of non significant (less than or equal to 50%) coronary lesions in 11 patients, one vessel disease in 33, two-vessel disease in 18 and three-vessel disease in 13 patients. Sensitivity of dobutamine-ECG test to detect multivessel (two- or three vessel) disease was 84%, specificity 64%, predictive value of a positive test: 62%, predictive value of a negative test: 85%, and diagnostic efficiency: 72%. In conclusion dobutamine-ECG is a highly sensitive test to diagnose multivessel disease in patients with non-complicated AMI. The specificity is lower, probably due to detection of peri-infarction ischaemia in cases of one-vessel disease. PMID- 2318229 TI - Coronary to bronchial artery anastomosis with bronchial steal syndrome demonstrated by thallium-201 myocardial tomoscintigraphy. AB - A case study is presented in which the bronchial steal syndrome is demonstrated by stress thallium-201 myocardial perfusion imaging. The various aspects of the syndrome are discussed. We conclude that bronchial steal syndrome may provoke severe myocardial ischaemia even in the absence of coronary artery stenosis. PMID- 2318230 TI - Delayed improvement of myocardial function after recanalization of a chronic coronary occlusion in a patient with intractable heart failure. AB - This case report describes the delayed improvement of left ventricular function by recanalization of an occluded coronary artery in a patient with intractable heart failure and three-vessel disease. The left anterior descending coronary artery was occluded distal to the first septal branch, the dominant right coronary artery had a diameter stenosis of 70-80% in its middle part, and the circumflex artery a proximal stenosis of 50%. Ventriculography revealed globally depressed left ventricular function with an ejection fraction of 16%. Successful recanalization and angioplasty of the occluded coronary artery resulted in a slow improvement of left ventricular function. Ultimate recovery of systolic performance (increase of ejection fraction from 16% to 48-51%) required more than half a year. It is speculated that stunned myocardium following chronic ischaemia is a consequence of vascular dysfunction. PMID- 2318231 TI - Basis for the application of calcium antagonists in neurology. Florence, May 25 27, 1989. Proceedings. PMID- 2318232 TI - Cerebrovascular effect of calcium antagonists. AB - Activity of calcium antagonists was assessed in microvessels (internal diameter 5 50 microns) isolated from rat brain. High KCl solution induced an increase of the lanthanum-resistant 45Ca influx and a marked reduction in microvessel diameter. Both responses to depolarization were inhibited by the calcium antagonists nimodipine and flunarizine. Binding studies with 3H(+)PN200-110 used as a specific ligand of Ca channels revealed the existence of voltage-dependent, stereoselective binding sites for dihydropyridine calcium antagonists. PMID- 2318233 TI - Shock wave monotherapy of staghorn calculi. AB - From June 1987 to October 1988, 52 staghorn calculi were treated without anesthesia by shock wave lithotripsy with the second-generation lithotriptor, Lithostar Siemens. 36 calculi were evaluated. Multiple sessions (n = 1-6) were necessary according to the size of the stone. The mean hospital stay for complete treatment was 7 days. Double-J stenting was used in 45% of the patients with calculi of less than 40 mm and in 81% of the patients with calculi of greater than 40 mm. After 3 months, 50% of the patients with calculi of less than 40 mm were free of stones, as were 43% of the patients with calculi greater than 40 mm. After 9 months, the stone-free rate rose to 75%. At 3 months, the success rate (stone free or residual fragments of less than 4 mm) is 87.5% and rose to 92% at 9 months. Two severe complications were observed: one patient with acute infected hydronephrosis with sepsis and one with perirenal hematoma. Shock wave lithotripsy monotherapy of staghorn calculi is possible in multiple treatment sessions. Double-J stenting is mandatory in most of the cases but, even in this condition, anesthesia is not necessary. PMID- 2318234 TI - Epidemiological case-control study on the etiology of bladder cancer in Turkey. AB - A case-control study of 194 patients with bladder cancer and the same number of age- and sex-matched hospital controls were interviewed to estimate the role of various factors on the etiology of bladder cancer in Turkey. There was a significant difference between the case and control groups on cigarette smoking (p less than 0.001), alcohol intake (p less than 0.001), Turkish coffee consumption (p = 0.01), and artificial sweeteners (p less than 0.05). The risks for alcohol and tobacco users increased in correlation with the duration of exposure. The risk of bladder cancer increased directly with the quantity and frequency of alcohol intake. Alcohol and coffee drinking was found to be a promoting factor when adjusted to smoking habits (p less than 0.05). No statistical comparisons could be made to clarify the risks attributed by occupation and place of residence due to small figures in each group. However, in farmers, there was a significant difference between the cases and controls on the use of artificial fertilizers and insecticides (p less than 0.01). People who were exposed to unspecified chemical substances were more prone to develop bladder cancer (p less than 0.001). We conclude that both personal habits and exogenous carcinogens play a role in the etiology of bladder tumors. PMID- 2318235 TI - Neoplastic thrombosis in the renal cancer. AB - Data pertaining to 193 patients with renal cancer, evaluated and treated in our department from 1966 to 1982, were subsequently examined and studied with regard to survival in relation to the pathological stage. In our experience the transluminal propagation of a tumor thrombus within the renal vein or the inferior vena cava, as an isolated condition, does not appear to worsen the prognosis as does the lymph node involvement. PMID- 2318236 TI - Value of selective reversible sacral nerve blockade in the diagnosis and treatment of the urge syndrome. AB - Interstitial cystitis, neurogenic disturbances of bladder emptying resulting from incomplete supranuclear lesions and idiopathic detrusor hyperreflexia are clinically always associated with frequency, nocturia, urgency or urgency incontinence (urge syndrome). These disturbances of bladder emptying are difficult to distinguish, even urodynamically. With selective sacral nerve blockade, it is possible to differentiate between forms urodynamically using a nerve-blocking anesthetic. Reversible selective sacral nerve blockade is also the treatment for idiopathic detrusor hyperreflexia. PMID- 2318237 TI - Hyperparathyroidism in metastases of prostatic carcinoma: a biochemical, hormonal and histomorphometric study. AB - Secondary hyperparathyroidism can develop as a result of bone metastases from prostatic cancer, but this has not been studied from the multiple aspects of biochemistry, hormonal status and histomorphometry. In 20 patients with stage-D prostatic cancer, a transiliac bone biopsy was performed for histomorphometric study. In all of them, molecular parathormone (PTH-M) and osteocalcin were determined by radioimmunoassay together with other parameters considered to be biological markers of bone remodelling. Of these 20 patients, only 2 (10%) had elevated PTH-M (240 +/- 20.6 pmol/l), differing significantly from the other 18 (58.6 +/- 11.7 pmol/l) and from controls (60.4 +/- 7.2 pmol/l). In the high PTH-M patients, corrected calcium was low (7.8 +/- 0.4 mg/dl) as compared to normal PTH M patients (9.2 +/- 0.5 mg/dl, p less than 0.001), and this was also the case for serum phosphorus (2.2 +/- 0.6 vs. 3.2 +/- 0.3 and 3.4 +/- 0.4 mg/dl, respectively p less than 0.001). Alkaline phosphatase was raised in the patient groups as compared to controls (p less than 0.001) and was higher in the high PTH-M group (362 +/- 58 vs. 224 +/- 62 U/l, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318238 TI - Urethral advancement technique for repair of distal hypospadias. AB - Eighty children with distal hypospadias were operated upon by this technique. It is a modification from the old Beck technique and is applicable only for distal types (coronal and subcoronal) with minimal chordae and rotation. The urethral meatus could be placed to the tip of the glans penis by mobilizing and advancing the urethra without constructing a neourethra. Children did not need catheterization or diversion. The average hospital stay was 2 days. Success rate was 98%. Children who developed fistulae were treated by simple closure of the defect. PMID- 2318239 TI - Twenty-year follow-up of primary mega-ureter. AB - 47 children diagnosed as having obstructed or non-refluxing, non-obstructed, primary mega-ureters were followed up by questionnaire. 2 patients had developed renal failure over 20 years, the remainder were free of urinary tract infection or hypertension. 21 of these patients were followed up with clearance and differential renal function studies. All but 4 kidneys associated with operated mega-ureters at long term follow-up had good function. PMID- 2318240 TI - Pressure-optimized lithotripsy with the Siemens Lithostar: successful and tissue protecting treatment of urinary stones. AB - With the Siemens Lithostar all kinds of urinary stones can be successfully treated at significantly lower pressure levels than with other commercially available lithotripters. Experimental and clinical experience indicates that for urinary stones there exists a pressure region between 200 and 400 bar (20-40 MPa) where lithotripsy can be performed successfully and the tissue can be protected. By calculation of isobar zones the pressure distribution of different lithotripters can be compared quantitatively. From this it becomes evident that the dynamic range of the Lithostar is optimized to that 'golden' pressure region. PMID- 2318241 TI - Study of the fetal kidney length growth during the second and third trimesters of gestation. AB - The fetal kidney length growth was studied in 240 kidneys taken from 120 staged human fetuses (74 males and 46 females) ranging in age from 10 to 36 weeks postconception. Each kidney was quantitatively evaluated considering its greatest longitudinal length. The data were correlated to the gestational age by using the allometric method (Y = bXk). Equations and growth curves of right and left kidneys, males, females and the whole sample during the second and the third trimesters are presented. This study has practical utility in the quantitative determination of the renal anomalies and in the determination of the gestational age. PMID- 2318242 TI - Androgen receptors--a method to measure functional behaviour in human prostatic cancer. AB - Androgen receptors were measured in soluble and nuclear fractions of tissues obtained from 25 patients. A method using mibolerone, a synthetic androgen, as a ligand is described. This method, which includes the presence of excess ORG 2058 to eliminate interaction with progesterone receptors, gives a reliable determination of androgen receptor content and has been used to predict response to hormonal treatment. However, the results suggest that the presence of functional receptor is not, in itself, a sufficient index of hormonal dependence of the tumour. PMID- 2318243 TI - One-stage urethroplasty for complicated urethral strictures using axial penile skin island flap. AB - Surgical repair of urethral strictures complicated by multiple scrotal/perineal urethrocutaneous fistulae (watering-can perineum) can be very problematic. The perineal/scrotal skin is either not available or is riddled with infection, fibrosis or granulomata and therefore unsuitable as a graft source. The presence of infection makes free grafts from other sites unlikely to survive. Furthermore, extensive fibrosis may prevent excision and re-anastomosis as well as internal urethrotomy. The absence of preputial skin in circumcised patients compounds these problems. We have used a one-stage, transverse vascularized cutaneous penile flap to repair 20 cases of these complicated strictures. The graft took in 100% and no absolute repair failure was registered. In spite of obvious pre operative infection, the result of repair was judged excellent in 17 patients (85%) and very fair in 3 (15%). PMID- 2318244 TI - Traumatic bilateral renal infarction. AB - Spontaneous recovery from biopsy-verified bilateral post-traumatic renal infarction in a 20-year-old patient is described, with clinical and renal stability maintained after 60 months of follow-up. A comprehensive analysis of recorded data yields no similar example, but several cases claiming subsequent viability after varying types of management bear clinical and histologic similarities. Management options may be influenced by these data. PMID- 2318245 TI - Giant leiomyoma of the kidney. AB - A rare case of giant renal leiomyoma presenting as a suprarenal mass is reported. This type of tumor seldom gives rise to other clinical symptoms. The angiographic appearance has no characteristic features. The treatment of choice is nephrectomy since it is impossible to make a correct preoperative diagnosis. PMID- 2318246 TI - Intracorporeal self-injection with epinephrine as treatment for idiopathic recurrent priapism. AB - Intracorporeal papaverine self-injection therapy has gained widespread acceptance in the treatment of impotence. Treatment for the opposite, recurrent priapism, is also possible with the same technique using a vasoconstrictive drug. We report a patient with idiopathic recurrent priapism successfully managed by intracorporeal self-injection with epinephrine. PMID- 2318247 TI - Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell-mediated immunity. AB - Previously we reported that activated T lymphocytes express a heparanase enzyme that degrades the heparan sulfate moiety of the proteoglycan of the extracellular matrix (ECM). Expression of the heparanase enzyme was found to be associated with the ability of activated T lymphocytes to penetrate blood vessel walls and accumulate in target organs. We recently found that relatively low doses of heparin administered to mice or rats inhibited T cell-mediated immune reactions. In the present study we investigated the effects in vitro and in vivo of the heparanase inhibitor, heparin, on the expression of T lymphocyte heparanase and on the ability of T lymphocytes to mediate a delayed-type hypersensitivity (DTH) reaction. We found that heparanase was induced by immunizing mice with antigen in vivo or by activating T lymphocytes with concanavalin A in vitro. Relatively low doses of heparin administered once daily in vivo (5 micrograms) or present in vitro (0.1 microgram/ml) inhibited the expression of heparanase induced by immunization or by concanavalin A incubation. Higher or lower doses of heparin did not have these effects. The same doses of heparin that inhibited expression of heparanase also inhibited the ability of the lymph node cells to migrate to a site of antigen and adoptively produce a DTH reaction. These findings suggest that modulation of cell-mediated immune reactions may be achieved by relatively low doses of heparin which inhibit expression of T lymphocyte heparanase. PMID- 2318248 TI - Specific deletion of the J-C delta locus in murine alpha/beta T cell clones and studies using transgenic mice. AB - A deletion event in the T cell receptor (TcR) delta locus has been characterized in a panel of mouse alpha/beta cytotoxic T lymphocyte (CTL) clones. Data presented here shows that J delta 1, J delta 2 and C delta are absent from functional CTL clones while a germ-line D delta 1 fragment is retained, thus suggesting a specific deletion of this region. We have investigated the possible significance of the J-C delta deletion by generating T cell lines from TcR alpha/beta transgenic mice. Unlike control T cell lines which included a T cell line derived from a beta transgenic mouse, the lines expressing the transgenic alpha/beta heterodimer have not deleted the C delta region. This strongly suggests that the J-C delta deletion event is not responsible for directing T cells to the alpha/beta lineage, but rather is involved in the rearrangement or transcriptional activity of the alpha locus. In addition, to ensure that the alpha/beta transgene does not have any inhibitory affects on the rearrangement of the delta loci in general, the gamma/delta expressing dendritic epithelial T cell (DETC) population was examined in TcR alpha/beta transgenic mice and alterations in this T cell subset were not found. This finding that normal gamma/delta DETC cells are present in alpha/beta transgenic mice, together with the data showing that the D delta 1 region remains in an unrearranged germ-line configuration in functional alpha/beta CTL, suggests that commitment to the alpha/beta or gamma/delta lineage is predetermined at a particular stage in early T cell ontogeny. PMID- 2318249 TI - Interleukin 4 receptors on normal human B lymphocytes: characterization and regulation. AB - Human interleukin 4 (IL 4) up-regulates the expression of CD23 on both resting and "in vivo" activated B cells but induces proliferation and/or differentiation only on "in vitro" activated B lymphocytes. Resting B cells express 360 high affinity IL 4 receptors (R) per cell (Kd = 25-75 pM). Activation of resting B cells with anti-IgM antibody or Staphylococcus aureus Cowan I (SAC) results in a two-to-threefold increase of IL 4R number without alteration of IL 4R affinity for IL 4. Flow cytometric analysis of biotinylated IL 4 binding shows that IL 4R expression is up-regulated on virtually all anti-IgM-stimulated B cells, but only on a subpopulation of larger cells among SAC-activated B lymphocytes. Culturing cells for 40 h with optimal concentrations of IL 4 does not significantly affect IL 4R levels on resting and anti-IgM-preactivated B lymphocytes but triples IL 4R levels on SAC-preactivated B cells. Removal of IL 4 from cell cultures results in a two-to-fourfold increase of IL 4R levels 2 h later, suggesting an increase in IL 4R turnover. Resting and activated B cells degrade 125I-labeled IL 4 at 37 degrees C. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of IL 4 binding molecules on resting, "in vivo" activated and anti-IgM-activated B cells reveals the same three species of 130, 80-75, 70-65 kDa. Thus, IL 4 displays its different biological activities on resting and activated B cells through IL 4R of the same affinity, gross biochemical structure and ability to mediate IL 4 degradation. PMID- 2318250 TI - Evidence that the level of the p55 component of the interleukin (IL) 2 receptor can control IL 2 responsiveness in a murine IL 3-dependent cell. AB - Although the role of interleukin 2 (IL 2) in mature T lymphocyte function is well documented, its effect on hematopoietic progenitor cells is less well characterized. Here we have used recombinant retroviruses to transduce and express a cDNA clone encoding the p55 component of the human IL 2 receptor (h p55), in a murine IL 3-dependent cell line, BAF3. While the parental cells do not respond to IL 2, the h-p55-expressing cells proliferate upon treatment with recombinant IL 2 after an initial lag period. The responsiveness of individual cell clones is correlated with their level of h-p55 expression, and can be inhibited by Tac monoclonal antibody. Furthermore, growth at limiting IL 2 concentrations selects a subset of cells expressing higher h-p55 levels from a bulk population. Detailed 125I-labeled IL 2 binding analysis on the highest h-p55 expressing clone detects the presence of 200 high-affinity (KD = 25 pM) IL 2 receptors. We therefore propose that the level of h-p55 expression governs the formation of high-affinity receptors, and hence IL 2 responsiveness in BAF3 cells. PMID- 2318251 TI - Type 6 and 19 pneumococcal polysaccharides coupled to erythrocytes elicit pneumococcal cell wall-specific primary IgM responses and capsular polysaccharide specific secondary IgG responses. AB - Previous results have shown that the primary murine antibody responses to vaccine preparations of type 6 (S6; Danish type 6A) or type 19 (S19; Danish type 19F) pneumococcal capsular polysaccharides consist entirely of IgM antipneumococcal cell wall carbohydrate (PnC)-specific antibodies. No capsular polysaccharide specific IgM antibodies were detectable by plaque-forming cell or enzyme-linked immunosorbent assay techniques. In this report, antibodies specific for S6 and S19 capsular polysaccharides were induced in secondary responses to chicken erythrocyte (CRBC) conjugates of S6 and S19. Essentially all detectable IgG produced in the secondary response was capsular polysaccharide specific and included all subclasses of IgG. In contrast, all detectable IgM produced in the primary response to S6-CRBC and S19-CRBC, and the IgM produced in the secondary response to S6-CRBC was not capsular polysaccharide specific since it reacted with PnC. Thus, there is a major change in the specificity of the primary IgM response compared to the secondary IgG response of mice immunized with S6-CRBC or S19-CRBC. Injection of PnC or any PnC-containing polysaccharide prior to immunization with S6-CRBC or S19-CRBC resulted in suppression of the primary IgM response. In contrast, only the capsular polysaccharide used in the immunizing polysaccharide-erythrocyte conjugate suppressed induction of the capsular polysaccharide-specific secondary IgG response. These results suggest that S6 and S19 capsular polysaccharide-specific IgG-producing memory B cells derive from capsular polysaccharide-specific precursors which do not produce detectable antibody after primary immunization. PMID- 2318252 TI - Synergy of tumor necrosis factor with protein kinase C activators on T cell activation. AB - The ability of tumor necrosis factor (TNF)-alpha to activate T lymphocytes in combination with other stimuli has been studied. TNF was strongly co-mitogenic with low doses of anti-CD3 antibodies or phorbol esters (those which are strong activators of protein kinase C, PKC) but poorly with phytohemagglutinin or concanavalin A. No synergism was seen with the calcium ionophore A23187. TNF was co-mitogenic with several phorbol esters known to activate PKC but was uneffective with inactive phorbol esters such as methyl-phorbol 12-myristate 13 acetate. Furthermore, H-7 a known inhibitor of PKC, inhibited the proliferative response of T cells induced by esters plus TNF. This effect took place at low doses of TNF and was also observed with purified T lymphocytes indicating that the effect of TNF was not dependent on accessory cells. This proliferative effect of TNF was inhibited by an anti-interleukin 2 receptor (IL2R) antibody, MAR 108, which blocks IL2 binding to its receptor. Although PKC activation induced CD25 (IL2R) expression but very little IL2 synthesis, TNF did not synergize by augmenting the synthesis of this lymphokine in peripheral blood lymphocytes stimulated with phorbol esters. By contrast, TNF strongly increased the membrane level of CD25 and to a lesser extent that of the activation antigen, 4F2, over the levels already induced by phorbol esters on T cells. More interestingly, TNF significantly increased the number of high-affinity IL2R on purified T cells in the presence of phorbol 12,13-dibutyrate. Our results indicate that TNF is co mitogenic with those stimuli which strongly activate PKC and suggest that TNF may play a role on T cell activation increasing the number of effective IL2/IL2R interactions when these are limiting. PMID- 2318253 TI - Identification and immunogenic properties of an 80-kDa surface antigen on a drug treated tumor variant: relationship to MuLV gp70. AB - Highly immunogenic tumor variants are generated by in vitro or in vivo treatment of L5178Y murine lymphoma cells with triazene derivatives. Most of these variants express new transplantation antigens which are not present on the original L5178Y tumor cells. In this study, a polyclonal syngeneic antiserum raised to one such variant (L5178Y/DTIC) was employed in immunoprecipitation studies of cell surface and metabolically labeled L5178Y/DTIC cells. One- and two-dimensional electrophoretic analyses of the immunoprecipitates detected a surface antigen of approximately 80 kDa. Additionally, a 45-kDa component was detected in the lysate of [35S]methionine-labeled cells. Anti-xenotropic MuLV gp70 serum precipitated material whose electrophoretic pattern was similar to that of the 80-kDa surface antigen. Sequential immunoprecipitation analysis revealed that the molecules reactive with the variant-specific antiserum were removed by the anti-xenotropic gp70 antibodies, whereas immunodepletion was only partial when the cell extract was first treated with the variant-specific antibodies. After Western blotting, the 80- and 45-kDa antigens precipitated by the variant-specific antibodies were injected intrasplenically into recipient mice. Only the animals sensitized with the 80-kDa antigen developed specific immunity to L5178Y/DTIC cells in that they displayed an increased frequency in CTL precursors (CTLp) to the variant cells. Sera from mice sensitized to the 80-kDa protein specifically inhibited the development of a primary CTL response to L5178Y/DTIC cells. PMID- 2318254 TI - Induction of interleukin 6 by human and murine recombinant interleukin 1 in mice. AB - Interleukin (IL) 6 is a pleistropic cytokine with activities, among others, on immune cells, hematopoietic precursor cells and hepatocytes. We have investigated the kinetics and amplitude of its in vivo induction in mice after injection of four different IL 1 species as well as murine (m) and human (h) tumor necrosis factor (TNF) and bacterial lipopolysaccharide (LPS) using a sensitive bioassay on 7TD1 cells to measure the IL 6 concentrations. Recombinant mIL 1 beta, administered as a single i.v. injection in mice, induced the appearance of IL 6 in the plasma with peak levels observed after 2 h. A dose-response correlation was found between serum IL 6 levels and injected IL 1 alpha concentrations at 3 and 8 h after the injection. We then compared the ability of h/mIL 1 alpha, h/mIL 1 beta, h/mTNF and LPS to induce IL 6 in mice. We found: (a) LPS is the most potent inducer of IL 6; (b) 3 h after injection, the four IL 1 preparations had induced IL 6 levels comparable with the IL 6 levels observed after TNF injection; (c) high doses of mIL 1, alpha or beta, but not hIL 1, resulted in a high IL 6 level persisting for over 8 h. We conclude that IL 1 is a potent inducer of IL 6 in vivo and that no major differences are observed between the four IL 1 preparations, as evaluated at 3 h after the injection. However, mIL 1 alpha and mIL 1 beta, in contrast to hIL 1 alpha and hIL 1 beta, induced a sustained IL 6 level over a longer time period. This pattern of prolonged IL 6 induction is even much more pronounced after mTNF injection, but not after hTNF injection. PMID- 2318255 TI - Prolactin and known modulators of rat splenocytes activate nuclear protein kinase C. AB - Prolactin (PRL) and other trophic factors rapidly activate a nuclear pool(s) of protein kinase C (nPKC) in purified splenocyte nuclei. The PRL also enhanced [2 3H]glycerol incorporation into nuclear mono- and triacylglycerol. An assay was devised which not only probed the ability of the hormone to activate protein kinase C (PKC) but also demonstrated the presence of nuclear substrates. Using this methodology, a biphasic concentration-response curve to PRL was observed. Heterologous species of PRL and various growth factors also activated nPKC. The PRL-induced nPKC stimulation was antagonized by various immunomodulators, G protein-coupling inhibitors, PKC inhibitors, a calmodulin inhibitor, and a peripheral benzodiazepine agonist and antagonist. A monoclonal antibody to PKC, anti-rat PRL antiserum and a monoclonal anti-rat PRL receptor antibody antagonized PRL-induced PKC-dependent nuclear phosphorylation, further implicating nPKC and a PRL receptor-mediated activation process. Nuclear PKC may be a major target for trophic regulation in response to both positive and negative growth signals. PMID- 2318256 TI - c-fos induction by estrogen in specific rat brain areas. AB - The present study was undertaken to determine whether estrogen modulates the expression of the c-fos gene in the CNS of rats. The analysis of the levels of c fos mRNA was performed by slot blot assay. Administration of estradiol to ovariectomized rats determined a rapid and transient increase in the levels of c fos mRNA in rat mid-brain and hippocampus, but not in the cerebellum (a brain area which does not express estrogen receptors). Such a change in the levels of c fos mRNA was not observed after administration of alpha-estradiol or other steroid hormones. The presence of an estrogen responsive element-like sequence, revealed in the 5' flanking region of the murine c-fos gene, strengthens the hypothesis that c-fos gene transcription is directly enhanced by the interaction of the estrogen receptor complex with the promoter region of the proto-oncogene. PMID- 2318257 TI - Effect of thromboxane A2 synthetase inhibition, singly and combined with thromboxane A2/prostaglandin endoperoxide receptor antagonism, on inositol phospholipid turnover and on 5-HT release by washed human platelets. AB - Differential effects on human platelet function of thromboxane A2 (TXA2) synthetase inhibition singly and of TXA2 synthetase inhibition combined with TXA2/prostaglandin endoperoxide receptor antagonism were revealed, using ridogrel as a probe. Ridogrel combines selective TXA2 synthetase inhibition with TXA2/prostaglandin receptor antagonism in one molecule: in washed human platelets, the compound reduces the production of TXB2 (IC50 = 1.3 X 10(-8) M) and increases that of PGF2 alpha, PGE2, PGD2 from [14C]arachidonic acid. Additionally, at higher concentrations (Ki = 0.52 X 10(-6) M), it selectively antagonizes the breakdown of inositol phospholipids, subsequent to stimulation of TXA2/prostaglandin endoperoxide receptors with U 46619. The latter happens in a competitive way with fast receptor association-dissociation characteristics. At low concentrations (1 X 10(-9)-1 X 10(-7) M) producing single TXA2 synthetase inhibition, ridogrel reduces the collagen-induced formation of TXB2 by washed platelets, but enhances [32P]phosphatidic acid (PA) accumulation and [3H]5 hydroxytryptamine (5-HT) release. At higher concentrations (1 X 10(-6)-1 X 10(-5) M) which additionally block U 46619-induced [32P]PA accumulation, ridogrel inhibits the [32P]PA accumulation and release of [3H]5-HT by human platelets stimulated with collagen. These observations, corroborated by results obtained with OKY 1581, sulotroban, indomethacin and human serum albumin, suggest a causal role for prostaglandin endoperoxides in the stimulation by TXA2 synthetase inhibition of platelet reactions to collagen. They reinforce the concept that TXA2 synthetase inhibition-induced reorientation of cyclic endoperoxide metabolism, away from TXA2 into inhibitory prostanoids, requires additional TXA2/prostaglandin endoperoxide receptor antagonism to achieve optimal anti platelet effects. PMID- 2318258 TI - The effects of phorbol esters on choline phospholipid hydrolysis in heart and brain. AB - The efflux of choline was determined in rat striatal slices, incubated chicken atria and perfused chicken hearts. 4 beta-Phorbol-12 beta,13 alpha-dibutyrate (PDB) and 4 beta-phorbol-12 beta-myristate, 13 alpha-acetate (PMA) were used to stimulate protein kinase C. The other phorbol esters, 4 beta-phorbol-13 alpha acetate (PAc) and 4 alpha-phorbol-12 beta,13 alpha-didecanoate (4 alpha PDD), known to be inactive, were tested to evaluate the specificity of the responses. PDB markedly enhanced the efflux of choline in all of the three preparations. The PDB-evoked efflux of choline in incubated chicken atria was equal to the net production of choline and, therefore, was not caused by translocation of intracellular free choline. After inhibition of the cholinesterase activity, PDB linearly increased the efflux of choline in rat striatal slices, but failed to alter the spontaneous efflux of acetylcholine. Thus acetylcholine did not serve as the source of the PDB-evoked efflux of choline. PMA was as effective as PDB, whereas PAc and 4 alpha PDD failed to alter the choline efflux in the perfused heart. Both infusion of a Ca2(+)-free EGTA-containing Tyrode solution and mepacrine reduced the spontaneous efflux of choline by about 40% and blocked the PDB-evoked efflux of choline. In contrast, a Ca2(+)-free solution without EGTA failed to alter the spontaneous and the PDB-evoked choline efflux. It is concluded that phorbol esters stimulate the hydrolysis of choline-containing phospholipids in heart and brain via activation of protein kinase C. PMID- 2318259 TI - A long-term study of 370 autotransplanted premolars. Part II. Tooth survival and pulp healing subsequent to transplantation. AB - The purpose of the present investigation was to determine the long-term prognosis of autotransplanted premolars with respect to tooth survival and pulpal healing. The material consisted of 195 patients aged 7 to 35 years, with a total of 370 autotransplanted premolars with observation period ranged from 1 to 13 years. Teeth transplanted with incomplete and complete root formation showed 95 per cent and 98 per cent long-term survival respectively: Pulp healing as evaluated by sensibility testing and radiographic signs of partial pulp canal obliteration was usually verified 6 months after transplantation. The frequency of pulpal healing (versus pulp necrosis), appeared to be closely related to stage of root development at time of transplantation. Teeth transplanted with incomplete and complete root formation showed 96 per cent and 15 per cent pulp healing respectively. Another and associated factor which could equally well predict pulpal healing was the diameter of the apical foramen of the graft. Finally, in teeth with completed root formation, the use of bursa with internal cooling and no extra-alveolar storage prior to transplantation seemed to increase the chance for pulpal healing. The present study indicates, that the size of the apical foramen and possibly the avoidance of bacterial contamination during the surgical procedure are explanatory factors for pulpal healing. PMID- 2318260 TI - A long-term study of 370 autotransplanted premolars. Part III. Periodontal healing subsequent to transplantation. AB - The purpose of the present investigation was to determine the long-term prognosis of autotransplanted premolars with respect to periodontal healing. The subjects consisted of 195 patients aged 7 to 35 years, with a total of 370 autotransplanted all operated and followed with a standard technique. The observation period ranged from 1 to 13 years. Periodontal healing as demonstrated radiographically was complete in most cases after 8 weeks. Root resorption occurring after transplantation was divided into surface-, inflammatory- and replacement resorption (ankylosis). Root resorption occurred in 52 of the transplanted teeth and was usually diagnosed within 6 months. Root resorption was found to be significantly related to increasing stage of root development and the stage of eruption at the time of transplantation. Subsequent orthodontic movement of teeth with completed root formation at the time of transplantation resulted in a slight increase in the frequency of both surface and inflammatory resorption. The present study indicates that trauma to the PDL of the transplant is the explanatory factor for the development of root resorption. PMID- 2318261 TI - A long-term study of 370 autotransplanted premolars. Part I. Surgical procedures and standardized techniques for monitoring healing. AB - Tooth autotransplantation has recently become a method of treating certain orthodontic problems. Over a 13-year period 370 premolar transplants were monitored by electrometric pulp sensibility testing and radiographic examination for pulp and periodontal ligament healing as well as root growth. This article describes the surgical technique as well as the precision of sensibility testing and radiographic examination for evaluating transplant healing. The sensibility response was found markedly related to the stage of tooth development but not to the type of premolar. The precision of sensibility testing (i.e. deviation of two consecutive measurements at a few weeks' interval) was found to range from 15-36 per cent for the different stages. Film holders were used to standardize the intraoral radiographic exposures. The precision percentage for the measuring technique of tooth length and crown width based on a single radiograph read twice (reading error) ranged from 1.1 to 1.8 with only small variations among the different types of premolar. The precision percentage of the radiographic exposure technique evaluated from two consecutive radiographs (measuring plus exposure error) was found to range from 1.2 to 4.2, again with small variations among the different premolars. The accuracy of the radiographic technique (i.e. deviation of radiographically determined tooth dimensions from the true values) was found to range from 2.0 to 2.9 with only small variation between the various types of premolar. In conclusion the evaluation of electrometric sensibility testing should take into account the stage of root formation of premolars. PMID- 2318262 TI - A long-term study of 370 autotransplanted premolars. Part IV. Root development subsequent to transplantation. AB - The purpose of the present study was to analyse the extent of root development subsequent to transplantation in a material of 370 transplanted premolars. Before transplantation, the grafts were classified according to stage of root development (i.e. quarters of root length and constriction of the apical foramen) and length of tooth development (measured in mm from the cusp tip to the apical foramen). At radiographic controls the extent of root formation was registered. These figures were compared to the final tooth length of 288 non-transplanted premolars from the present material as well as to tooth length determinations of 534 premolars extracted for orthodontic purposes. Furthermore, intra-individual and inter-individual differences in tooth length were examined in a skull material with 40 pairs of premolars. These method studies indicated that root growth was probably determined genetically with great right-left accuracy and variation related to location of premolar (maxilla or mandible) and sex. A statistical analysis of the transplant material revealed that stage as well as length of tooth development assessed prior to transplantation were significantly related to final tooth length after transplantation. In most cases of transplantation performed at early stages of root development, a reduction in the final root length was seen. When a qualitative analysis of root development was performed in teeth with incomplete root formation at the time of transplantation, and where a homologous non-transplanted premolar was present, it was found that 14 per cent showed total arrest of root formation, 65 per cent partial arrest whereas 21 per cent showed no arrest (i.e. normal root formation). Premolars in ectopic position in the mandible before transplantation showed a significantly reduced root growth compared to matched pairs with normal position of the tooth graft. The present study indicated that no, partial or total damage to the Hertwig's epithelial root sheath was probably the explanatory factor for variations in root growth. PMID- 2318263 TI - Early modifications of nucleic acid metabolism and nuclear lipid biosynthesis associated with antiproliferative activity of interferon-alpha on Daudi lymphoma cells. AB - The effect of human recombinant DNA interferon-alpha type A (rIFN alpha A) on nuclear lipid biosynthesis and on in vitro nucleic acid synthesis was investigated in Daudi lymphoma cells sensitive (Daudi Is) or resistant (Daudi Ir) to the antiproliferative activity of this glycoprotein. In the Daudi Is studied at 90 min and up to 8 h, relative proportions of 3H-labeled nuclear lipids were reproducibly altered as compared to controls: phosphatidylcholine increased while phosphatidylserine and total neutral lipids decreased. These changes were not detected in parallel studies of the whole cell extracts. No significant changes in the profiles of nuclear lipids were observed in Daudi Ir. Decreased rates of alpha DNA polymerase and of RNA transcription were evident within 90 min in the Daudi Is nuclei but not in untreated controls or nuclei from rIFN alpha A-treated Daudi Ir cells, thus suggesting a possible relationship of the rapid alterations of nuclear lipid biosynthesis in Daudi Is cells to the rIFN alpha A antiproliferative activity. PMID- 2318264 TI - Effects of cell heterogeneity on production of polypeptide growth factors and mesoderm-inducing activity by Xenopus laevis XTC cells. AB - The Xenopus laevis XTC cell line has been analyzed for the production of polypeptide growth factors and mesoderm-inducing activity. By the use of specific biological assays, it is shown that XTC cells produce a growth factor functionally related to the platelet-derived growth factor (PDGF) and two transforming growth factor (TGF) beta-like activities. Mesoderm-inducing activity, as measured on X. laevis ectodermal explants from stage 10 embryos, was found to coelute on a Bio-Gel P-100 column with one of the TGF beta-like activities at an apparent molecular weight of 6-10 kDa. Analysis of the DNA content from XTC cells by flow cytometry demonstrated that the cell line is heterogeneous and consists of both tetraploid and diploid cells. Cloning of the XTC cells and selecting single-cell colonies on the basis of their ability to grow in soft agar resulted in the isolation of several homogeneous, morphologically different clonal derivatives. Analysis of conditioned medium from these clonal derivatives showed that only one of them, the only diploid line among six investigated, produced a strong heat- and acid-stable mesoderm-inducing activity that induced notochord and muscle formation in stage 10 X. laevis ectodermal explants. The relation between this activity and a recently described TGF beta-like mesoderm-inducing factor obtained from XTC-conditioned medium will be discussed. In conclusion, a clonal cell line derived from X. laevis XTC cells which provides a good source for further characterization of mesoderm-inducing factors has been established. PMID- 2318265 TI - Modulation of natural killer cell activity by surface phosphorylation reactions. AB - To determine whether phosphorylation of cell surface proteins is involved in NK cell activity, the phosphorylation patterns of a rat NK cell line (RNK-16) incubated with 12.5 microM [gamma-32P]ATP were characterized before and after exposure to YAC-1 cells, which serve as targets for killing, and K562 cells, which are not killed by RNK-16 cells. By 51Cr release assays, the inhibitory effect of ATP on RNK-16 killing activity previously reported was corroborated. RNK-16 cells prelabeled with 12.5 microM ATP show enhanced labeling of a 70- to 72,000-Da protein after exposure to unlabeled target YAC-1 cells but not after exposure to K562 cells. A protein of similar apparent molecular size is also labeled upon exposure of RNK-16 cells to OX-34, an antibody which binds and inhibits killing, as well as upon exposure to OX-18, which also binds but does not inhibit NK activity. These findings are indicative of the activation of a kinase with high affinity for [gamma-32P]ATP, which phosphorylates an endogenous surface substrate of 70-72,000 Da upon binding of macromolecules to the RNK-16 cells. RNK-16 cells, previously labeled with micromolars [gamma-32P]ATP and subsequently treated with millimolars unlabeled ATP, showed loss of label from a 110,000-Da protein component, indicative of the rapid turnover of a phosphate group on a surface protein. Thus, extracellular ATP enhances the phosphorylation of a 70- to 72,000-Da component upon binding of RNK-16 cells to target cells or upon binding of antibodies at micromolar concentrations of ATP and catalyzes the loss of phosphate from a 110,000-Da component at millimolar concentrations of ATP. These findings reflect a complex repertoire of surface phosphorylation changes which occur in RNK-16 cells. PMID- 2318266 TI - Communication compartments in the post-trochal ectoderm of the mollusc Lymnaea stagnalis. AB - Cell-to-cell communication via gap junctions provides a pathway for the transfer of small molecules and ions which may be significant for control of metabolic cooperation, cell proliferation, and differentiation. We have assessed the patterns of gap junctional communication in embryos of the mollusc Lymnaea stagnalis during the subdivision of the post-trochal ectoderm into developmental domains. We have microinjected the tracer Lucifer Yellow CH and subsequently analyzed its transfer to other cells. The post-trochal ectoderm of mollucs develops the shell field, the foot, and the stomodeum anlagen. We have found that the cells within the separate anlagen are well dye-coupled but poorly coupled to cells of adjacent anlagen. These results indicate that in Lymnaea embryos the specification of the different developmental domains is associated with the development of corresponding dye-coupling compartments. PMID- 2318267 TI - Ascorbic acid phosphate stimulates type IV collagen synthesis and accelerates adipose conversion of 3T3-L1 cells. AB - We showed that the synthesis and secretion of type IV collagen, entactin, and laminin were enhanced when adipose conversion of 3T3-L1 cells at confluence was stimulated by hormones (Y. Aratani and Y. Kitagawa (1988) J. Biol. Chem. 263, 16163-16169). Ascorbic acid phosphate (Asc-P) stimulated the synthesis and secretion of type IV collagen and other collagens from both 3T3-L1 preadipocytes and adipocytes. The synthesis and secretion of laminin and entactin were not affected by Asc-P. The continuous addition of Asc-P stimulated cell growth and increased cell density at confluence 1.3-fold. Concomitantly, Asc-P remarkably accelerated the emergence of lipoprotein lipase, glycerophosphate dehydrogenase, and Oil Red O-stainable lipid droplets. These findings suggest an important role for type IV collagen in adipocyte differentiation. PMID- 2318268 TI - A Mr 80K hepatocyte surface protein(s) interacts with basement membrane components. AB - We have identified a Mr 80K cell surface protein(s) from adult rat hepatocytes that binds basement membrane components, including collagen IV, heparan sulfate proteoglycan, and laminin. Freshly isolated hepatocytes were cell surface-labeled with 125I using the lactoperoxidase-catalyzed method, and detergent-solubilized membrane proteins were chromatographed on affinity columns prepared with purified basement membrane components. A Mr 80K protein was eluted with 0.15-1 M NaCl from a collagen IV column. Two proteins (Mr 80K and 38K) were eluted from a heparan sulfate proteoglycan column. The larger protein was also eluted from a column made with heparan sulfate side chains. Several proteins (Mr 80K, 67K, 45K, and 32K) bound to an affinity chromatography column made with the laminin A chain derived synthetic peptide PA22-2, which is active for promoting cell attachment. When fractions eluted from these columns were analyzed by two-dimensional gel electrophoresis, the Mr 80K proteins showed similar patterns with a pI ranging from 8 to 9. The Mr 80K protein(s) may have an important role in the interaction of hepatocytes with basement membrane. PMID- 2318269 TI - Acridine orange-induced precipitation of mouse testicular sperm cell DNA reveals new patterns of chromatin structure. AB - Precipitate resulting from interaction between certain intercalators, such as acridine orange (AO), and nucleic acids can be detected by electron microscopy. Formation of precipitate in nuclei of live cells is modulated by chromatin structure. Susceptibility of in situ DNA to precipitation was studied in mouse testicular germ cells during various stages of sperm maturation. DNA in round spermatid chromatin, similar to somatic cell euchromatin, was rather resistant to precipitation; the electron-dense precipitate was granular and randomly distributed. DNA in elongated spermatids was more susceptible to precipitation; the products were in the form of fibers. At early stages of spermatid maturation these fibers were distributed uniformly throughout the entire nucleus. At later stages, the products appeared as approximately 25-nm-thick fibers arranged longitudinally in arrays within the nucleus. With further cell maturation, fibers in the anterior portion of the nucleus appeared to fuse, forming homogeneously dense product. These fibrous products likely represent AO interactions with DNA in chromatin in which transition proteins had replaced histones. Changing patterns of these precipitated fibers likely reflect progressive stages of chromatin condensation, which starts at the center and anterior portion of the nucleus where the fibers coalesce. Mature sperm cell DNA, known to be complexed with protamines, was more resistant to AO-induced precipitation. The data suggest that precipitation induced by AO and monitored by electron microscopy may be a useful probe of nuclear chromatin structure. PMID- 2318270 TI - Comparison of membrane phospholipids of the rabbit and pig crystalline lens. AB - Crystalline lenses excised from 5-7-month-old rabbits and pigs were extracted for lipids with chloroform/methanol, 2/1 using the Folch method. The extracted crude lipids were analyzed at 202 MHz by 31P-NMR spectroscopy. Twelve membrane phospholipids were detected. Both rabbit and pig phospholipid profiles contained phosphatidylcholine (PC), lysophosphatidylcholine, phosphatidylcholine plasmalogen, phosphatidylethanolamine (PE), phosphatidylethanolamine plasmalogen (PE plas), phosphatidylserine, sphingomyelin (SPH), and an uncharacterized phospholipid. In addition, pig lens profiles contained lysophosphatidylethanolamine, phosphatidylinositol, cardiolipin and phosphatidylglycerol. The data indicate that these two animal models have significant differences in membrane phospholipid profiles. In each species, however, the bulk phospholipid component resides in the neutral phospholipids PC, PE, PE plas, and SPH. PMID- 2318271 TI - Cornea fluid dynamics. II. Evidence for transport of radiolabelled albumin in rabbits by bulk flow. AB - Transport of radiolabelled albumin in vivo has been measured in cornea. In anaesthetized rabbits, a 1-10 nl mixture of either 125I- or 131I-labelled human serum albumin and fluorescinthiocarbamoyldextran was injected with micropipettes under guidance of a fluorescent microscope. The injection sites were a spot 3 mm from limbus and the cornea centre, and the sites were localized by a template fitting the cornea exactly. Four, 12, 20 and 30 hr after the injection, the rabbits were reanaesthetized, and enucleated after being killed with an overdose of anaesthetic. The bulbi were frozen, and dissection of cornea performed in the cold room using the template described above and a stereomicroscope. Numbered samples were obtained, and isotope distribution measured. In the experiments lasting for 20 hr, about 55% of the isotope was recovered, giving a transfer coefficient of 0.4-0.5 per day. A common pattern of isotope distribution was observed independent of duration of isotope equilibration; peripherally injected isotope moved preferentially in central direction, indicating that fluid is transported by bulk flow and diffusion from peripheral to central cornea. Centrally injected isotope moved symmetrically from the injection point, as expected from transport by diffusion alone. Data from experiments with isotope injection in the cornea centre allowed the calculation of a diffusion coefficient for albumin along cornea of 2.19 x 10(-7) cm2 sec-1. PMID- 2318272 TI - D-[3H]galactose incorporation into glycogen in retinal cone cells. AB - Previous studies have shown that bovine retinas incubated with [3H]galactose incorporated it, unmodified, into large molecules. Light and electron microscope autoradiography showed a significant proportion of the label to be in cone inner segments, and pulse-chase studies showed it was subsequently transported to the synaptic pedicles. In this report, evidence is presented to show that the galactose-labelled macromolecules are resistant to hydrolysis by proteolytic enzymes, testicular hyaluronidase, chondroitinase ABC, beta-glucosidase and beta glucuronidase, but are readily degraded by alpha-amylase and beta-galactosidase, and to a lesser extent by beta-amylase. Treatment with alpha-amylase also leads to specific removal of radioactivity from cone inner segments and pedicles, as judged by light-microscopic autoradiography. These studies appear to indicate that the cone-specific galactose label is in glycogen or glycogen-like molecules. PMID- 2318273 TI - The effect of photocoagulation on the oxygenation and ultrastructure of avascular retina. AB - Panretinal photocoagulation has been shown to raise preretinal oxygen tension in cats and monkeys breathing 100% oxygen. However, in normoxia, there is no significant difference between normal and photocoagulated areas. This is thought to be due to autoregulatory vasoconstriction of the retinal circulation. In avascular rabbit retina, photocoagulation effects on retinal oxygenation can be studied without the influence of retinal vascular autoregulation. We measured normoxic preretinal oxygen tension of normal and photocoagulated rabbit retina at 1, 7, 14 and 28 days after photocoagulation using polarographic oxygen electrodes. For all time points, preretinal oxygen tension of photocoagulated retina (42 +/- 14 torr; mean +/- S.D.) was higher than untreated retina (14 +/- 10 torr; mean +/- S.D., P less than 0.001). Light and electron microscopy of lasered retina showed that the improved oxygenation corresponded to loss of mitochondria-rich inner segments of the photoreceptors. PMID- 2318274 TI - Fluorophotometric assessment of blood-retinal barrier function after white light exposure in the rabbit eye. AB - Fluorophotometry was performed in 14 rabbits after exposure of one eye to white light with an energy insufficient to cause visible phototoxic retinal damage as determined by ophthalmoscopy and fundus photography. Fluorescence measurements in the vitreous were performed before and 1 hr after i.v. injection of fluorescein. Ratios between the fluorescein concentrations in the exposed and in the non exposed fellow eye were calculated after correction for the autofluorescence. The average ratio directly after light exposure had significantly increased (P = 0.005) as compared to pre-exposure values and was maximal one day after exposure (P less than 0.005). Four days after exposure the ratios had returned to pre exposure values (P greater than 0.05). A significant linear correlation between age and the ratios directly after exposure was found (r = -0.67; P less than 0.01). Signs of phototoxic retinal damage were not found on ophthalmoscopy and fundus photography, nor on light and electron microscopic examination of the retinal pigment epithelium, neuro-retina or retinal capillaries 1 and 4 days after light exposure. A fluorophotometric assessment of the blood-retinal barrier (BRB) function after white light exposure appeared to be a more sensitive parameter of light-induced damage than morphological examination since light exposures at retinal irradiance levels below the threshold for ultrastructural damage resulted in a temporary BRB dysfunction that could be detected by fluorophotometry but not by the other methods. PMID- 2318275 TI - Association of hereditary cataracts in strain 13/N guinea-pigs with mutation of the gene for zeta-crystallin. AB - Congenital nuclear cataracts transmitted by an autosomal dominant gene are present in a line of strain 13/N guinea-pigs. Studies on the lens proteins from these animals demonstrate changes in both the composition and structure of the crystallins relative to normal controls. The most prominent difference is in the zeta-crystallin, a taxon-specific crystallin which has been shown to be related to the alcohol dehydrogenases. In animals homozygous for the cataract phenotype the normal zeta-crystallin polypeptide is absent from the lens. Quantitation is difficult in the cataractous lenses from heterozygotes because of protein changes secondary to opacification: however in liver and kidney which have catalytic levels of the protein, the concentrations are approximately half that present in tissue from normal control animals. These findings suggest that in the cataractous animals a mutation has occurred in the gene for zeta-crystallin. In addition, a novel protein which is very similar to zeta-crystallin is synthesized only in the lenses of animals with cataract. This protein appears to be the product of the mutant gene for zeta-crystallin. These data support the hypothesis that this hereditary congenital cataract results from a specific mutation in the zeta-crystallin gene. PMID- 2318276 TI - Localization of UV-induced changes in mouse lens. PMID- 2318277 TI - Paraformaldehyde fixation and some characteristics of lens proteins as measured by Raman microspectroscopy. PMID- 2318278 TI - A technique for isolation of the photoreceptor layer from other neurons in the human retina. PMID- 2318279 TI - Decrease of cholesterol concentration in human erythrocyte ghosts in old age. AB - The lipid composition of the erythrocyte membrane ghosts of 95 relatively healthy elderly subjects was compared between four age groups: 70 to below 75 years (I), 75 to below 80 (II), 80 to below 85 (III) and 85 to below 90 years of age (IV). The molar ratio of phospholipid to cholesterol (PL/CH) in the erythrocyte ghosts increased with advancing age. Whilst PL levels did not change significantly, a decrease of membrane cholesterol was found. Therefore, the red cell membrane cholesterol seems to parallel the well-known pattern of variation of mean plasma total cholesterol and LDL cholesterol concentrations with age: an increase to a maximum in the sixth decade of life, and a decline thereafter. The processes which are responsible for these changes in cholesterol level with age have not been delineated. However, the findings suggest that one might get different results in studies of age-dependent membrane lipid alterations if rough age group divisions are made (below 30 years of age vs. over 70 years) or to subdivide the group of the elderly. PMID- 2318280 TI - Age-related differences in body weight loss in response to altered thyroidal status. AB - To determine whether age-related differences in body weight loss in hyperthyroidism could be related to caloric intake, the body weight and food consumption of Fischer 344 male rats were monitored every other day for four weeks. Six-month-old (young) rats were compared to 16-month-old rats (intermediate age) and 25-month-old (aged) rats. Hypothyroidism was induced with 0.025% methimazole in the drinking water for four weeks. Hyperthyroidism was induced with triiodothyronine (T3) injections (15 micrograms/100 g body weight i.p.) for the last 10 days of observation. A group of young rats pair fed with aged rats was included as a control group. The body weight changes of aged rats were similar to hypothyroid young rats. An index of T3 catabolic effect was calculated based on the net weight loss and food intake. This index was not different in aged rats compared to young rats. The apparent hypersensitivity of aged rats to T3 as evidenced by excessive weight loss could totally be attributed to decreased caloric intake. It is concluded that aged rats compared to the young are not more sensitive to the overall catabolic effects of thyroid hormones. PMID- 2318281 TI - Effect of gemfibrozil on erythrocyte membrane lipids in geriatric patients. AB - Twenty geriatric patients with primary or secondary hyperlipidemia and suffering from various other diseases received for three weeks once daily 900 mg gemfibrozil. The hyperlipidemia had not been treated before, and a cholesterol reduced diet did not succeed in lowering total cholesterol below 6.75 mmol/l (260 mg/100 ml) and serum triglycerides below 1.97 mmol/l (175 mg/100 ml). The purpose of this study was to analyze the lipid composition of the erythrocyte membrane, serum lipids and rheological parameters before and after the therapy. Mean serum total cholesterol and triglyceride content decreased significantly by 16.3% (p less than 0.05) and 35.2% (p less than 0.01) on average, respectively. Aggregation of thrombocytes and of erythrocytes, thrombin time and partial thromboplastin time slightly varied during the three weeks' treatment, but without statistical significance. The content of total long-chain saturated fatty acids in the phospholipid fraction of the erythrocyte membrane decreased slightly from 41.3% to 40.9% (p less than 0.05), whereas the total w6-unsaturated fatty acids without the precursor linoleic acid increased by about the same extent from 15.66% to 16.0% (p less than 0.05). The molar ratio of phospholipid to cholesterol content decreased significantly (p less than 0.01) due to a reduced phospholipid content at the end of the therapy. In conclusion, in addition to reducing the serum lipids, gemfibrozil slightly effects the lipid composition of erythrocytes, but the effects of the varied concentrations of long-chain saturated and long-chain w6-unsaturated fatty acids in the phospholipid fraction on membrane fluidity might be compensated, at least partly, by the decrease of the ratio of membrane phospholipid to cholesterol. PMID- 2318282 TI - Age-related changes in rat liver phospholipid transfer activity. AB - The age-induced changes in the liver cytosol phospholipid transfer activity of male and female rats have been investigated. These changes were found to be closely related to the age-induced alterations in the two major microsomal phospholipids--phosphatidylcholine and phosphatidylethanolamine. Regression analysis indicated a linear correlation between the phospholipid transfer activity and the level of phosphatidylcholine (positive) and phosphatidylethanolamine (negative) in liver microsomes of both male and female rats. PMID- 2318283 TI - Influence of aging on vitamin A transport into the lymphatic circulation. AB - Vitamin A is a lipid soluble essential dietary micronutrient. Because aging individuals have elevated serum levels of vitamin A, we tested the intestinal absorptive capacity of the vitamin in aging rats by measuring the appearance rate of vitamin A in the lymphatic circulation as a measure of intestinal absorption. We infused the vitamin in a physiological concentration of 350 nM into the proximal jejunum of groups of Sprague-Dawley rats 2 to 23 months of age. Lymph was collected for 6 h and vitamin A radioactivity was measured. Lymph flow rate over 24 h ranged from 16 +/- 3.1 ml in the oldest to 21.5 +/- 2.4 ml in the youngest animals. Vitamin A transport into lymph was highest at 23 months of age, reaching 7869 +/- 154 pmol/6 h as compared to 6732 +/- 106 pmol/h at 2 months (p less than .01). The increase in vitamin A absorption with aging represented an increase from 35.6% of the infused vitamin at 2 months to 41.6% at 23 months of age. Because of the cumulative storage of vitamin A in the liver this increase in absorption and lymphatic appearance is of nutritional and metabolic significance. Increased lymphatic appearance of the vitamin could explain its higher absorption and serum levels in aging individuals. PMID- 2318284 TI - Effect of aging on intestinal biotin transport in the rat. AB - The influence of aging of biotin intestinal transport was examined in Fisher 344 rats (3- 12- and 24-month old) using a brush border membrane vesicle (BBMV) technique. In all age groups examined, transport of biotin as a function of concentration was saturable in the presence of a Na+ gradient (out greater than in), but was lower and linear in the presence of a choline gradient (out greater than in.). The Vmax of the biotin transport process was found to be significantly (p less than 0.01) higher in 24-month-old rats compared to 3- and 12-month old rats. On the other hand, the apparent Km of the biotin transport system was similar in all age groups. We also measured plasma levels of biotin in the different age groups. The mean plasma levels of biotin in 24-month-old rats was found to be significantly higher than that of 3-month (p less than 0.005) and 12 month (p less than 0.025) old rats. These results demonstrate that aging is associated with an increase in biotin intestinal transport. This increase appears to be due to changes in the activity (and/or number) but not the affinity of the biotin transport system. Furthermore, an increase in plasma biotin levels was observed with aging, which might be a consequence to the increase in the vitamin's intestinal transport. PMID- 2318285 TI - Axotomy enhances the outgrowth of neurites from embryonic rat septal-basal forebrain neurons on a laminin substratum. AB - Previous studies have suggested that embryonic (nonaxotomized) and regenerating central nervous system neurons differentially respond to the same substrata. In the present study, we have used an in vitro model to test the ability of laminin and type I collagen to promote the outgrowth of neurites from nonaxotomized and axotomized, embryonic septal-basal forebrain (SBF) neurons. Neurons within explants derived from Embryonic Day (E) 15 rats extended neurites that demonstrated similar growth characteristics on a collagen or laminin substratum. E15 neurons could be induced to extend longer neurites on laminin if they were axotomized in vitro and subsequently replated onto a laminin substratum. The carbocyanine dye DiI indicated that neurons which were axotomized could survive and regenerate processes. These regenerating neurites grew 27% longer on laminin than they did on collagen. Similarly, neurons that were axotomized in situ, i.e., E18 SBF neurons, extended neurites that were 29% longer on a laminin substratum. In contrast, E15 explants that were maintained in suspension culture prior to being plated onto a substratum exhibited similar growth on laminin or collagen. The increase in regeneration by E15 neurons on laminin was augmented, by 22%, if nerve growth factor was supplemented to the culture medium. These results demonstrate that laminin is a better substratum, as compared to collagen, for the elongation of neurites from axotomized SBF neurons. Nonaxotomized neurites, on the other hand, do not appear to prefer one substratum over the other. Furthermore, regeneration from embryonic, SBF neurons on laminin is augmented if NGF is used simultaneously. PMID- 2318286 TI - Truncated IGF-1 exerts trophic effects on fetal brain tissue grafts. AB - Truncated IGF-1 (tIGF-1), a form of IGF-1 identified in the human brain, has been suggested, from in vitro experiments, to exert neurotrophic effects on developing fetal brain tissue. We studied the effects of tIGF-1 and IGF-1 on small defined areas of the developing central nervous system by using the in vivo model of intraocular transplantation which allows for direct observations of graft survival and growth. Truncated IGF-1 was found to significantly enhance the growth of fetal spinal cord (Embryonic Day (E) 14) and parietal cortex (E16-17) grafts transplanted to the anterior chamber of the eye of adult rats. tIGF-1 increased the volume of cerebral cortex grafts by approximately 100% and of E14 spinal cord grafts by approximately 50%. E18 spinal cord grafts and hippocampal grafts were not stimulated by tIGF-1 as compared to controls given HSA. Effects in cortex were seen with tIGF-1 using concentrations down to at least 10 ng/microliters. Interestingly, intact IGF-1 had no effect on cortical grafts. These findings show for the first time, using an in vivo system, that tIGF-1 is a potent stimulator of growth of grafted fetal cortex cerebri and spinal cord and suggest a possible role for endogenous tIGF-1 in cortical and spinal cord development. PMID- 2318287 TI - The response of rubrospinal neurons to axotomy in the adult opossum, Didelphis virginiana. AB - To provide endpoints for developmental studies of rubrospinal plasticity in the North American opossum, we have attempted to determine the degree to which rubrospinal neurons survive axotomy in the adult animal. Bilateral or unilateral injections of the long-lasting fluorescent marker fast blue were made into the T 10 or the T-11 segment of the spinal cord to label rubrospinal neurons, and 7 days later, the rubrospinal tract was cut unilaterally four segments rostral to the injection(s). In cases with unilateral injections, the lesion was made ipsilateral to the injection. The animals were allowed to survive for 30-60 days before being sacrificed and perfused so that sections through the red nuclei could be examined for labeled neurons. The results show that most axotomized neurons survived the lesion, suggesting that lesion-dependent cell death is not a major factor in the failure of the rubrospinal tract to regenerate in the adult animal. PMID- 2318288 TI - Audiogenic seizure severity and hearing deficits in the genetically epilepsy prone rat. AB - Hearing deficits have been observed in rodents that are susceptible to audiogenic seizures (AGS), including the genetically epilepsy-prone rat (GEPR). AGS susceptibility can be induced in normal animals by treatments that damage the cochlea. In this study, we measured the relative degree of hearing loss in animals from the GEPR substrains that exhibit different degrees of AGS severity and examined the relationship between the deficit and the AGS severity. Auditory brain stem response (ABR) thresholds to clicks in the GEPR substrain that exhibits exclusively maximal AGS severity (GEPR-9) were significantly elevated, and latencies for ABR peaks I, III, and IV were significantly increased as compared to normal Sprague-Dawley rats. ABR thresholds for the substrain of GEPRs were even higher than those in the GEPR-9, and ABR waveforms were distorted. ABR peak IV was significantly longer than normal in the GEPR-3 substrain, as were mean interpeak intervals and central conduction times. These data indicate that significant hearing deficits occur in the GEPR-3 substrain. In non-AGS susceptible progeny of the GEPR-9 [GEPR-0(9)], ABR thresholds were not significantly different from normal. These data along with studies of ABR thresholds in thyroid-deficient rats suggest that an inverted U-shaped relationship exists between hearing deficit and AGS severity. That is, moderate threshold elevations are associated with increasing AGS severity, but when the hearing deficit exceeds a certain level, a decrement in AGS severity occurs. PMID- 2318289 TI - In vivo electrophysiological analysis of lucifer yellow-coupled hippocampal pyramids. AB - Small transient all-or-none depolarizations (also termed in the literature fast prepotentials, spikelets, pseudospikes, d-spikes, or short latency depolarizations) and their association with lucifer yellow (LY) dye-coupling were analyzed in CA1-CA3 hippocampal pyramidal cells in urethane anesthetized rats. It was found that (a) 15 of the 24 LY-injected pyramidal neurons (63%) showed dye coupling; (b) spontaneous, anti- and orthodromically evoked spikelets (3-7 ms in duration; 3- to 12-mV peak) were recorded in 40 of 95 cells (42%); (c) there was a significantly higher probability of dye-coupled neurons with spikelets and of uncoupled ones without spikelets; (d) spikelet waveform and amplitude were unaffected by spontaneous or imposed polarizations; (e) large hyperpolarizations could reduce the rate and even prevent spikelets; and (f) spikelets could precede or follow spikes, the latter were more frequent with large depolarizations. Electrophysiological findings, and the association of dye-coupling and spikelets, suggest strongly that at least some spikelets are coupling potentials. This implies that pyramidal cells may be electronically coupled under physiological conditions. PMID- 2318290 TI - Increased glucose use in the hypoglossal nucleus after hypoglossal nerve transection in aged rats. AB - We used [2-14C]deoxyglucose as a marker of increased metabolism of the hypoglossal nucleus after transection of its nerve. We studied this metabolism in 3-, 12-, and 24-month-old rats. We found an increase in glucose uptake in the control nucleus of 24-month-old rats which was significant when compared to that of 3-month-old rats. We also found a twofold increase in the difference between glucose uptake on the side of nerve transection compared to the control side in old rats. PMID- 2318291 TI - Nucleus basalis lesions fail to induce senile plaques in the rat. AB - Fourteen months after receiving bilateral ibotenic acid lesions of the nucleus basalis magnocellaris (NBM), male rats demonstrated impairment in spatial learning in a water maze task, increased incidence of high voltage spindles, and significant depletion of cortical choline acetyltransferase (ChAT) activity. Histological evaluation revealed decreased acetylcholinesterase (AChE) staining but no plaque-like structures in the cortex. PMID- 2318293 TI - Alpha thalassaemia in two Spanish families. AB - Two Spanish families with alpha thalassaemia, including 4 individuals with Hb H disease, are described. DNA mapping shows that, in addition to the common alpha thalassaemia determinant (-alpha 3.7), a different and previously unreported allele is present in each family. In one, there is a deletion of 10.5-12 kb of DNA including both alpha genes (--SPAN). In the other, a deletion of more than 100 kb has removed the entire alpha globin gene complex (--BR). PMID- 2318292 TI - Evaluation of microcytosis using serum ferritin and red blood cell distribution width. AB - Out of 104 patients with microcytosis (MCV less than 80 fl), 69% had an iron deficiency, 21% a chronic disease and 10% hemoglobinopathy or thalassemia trait. The absence of bone marrow iron stores or the response to iron supplementation were used to establish the diagnosis iron deficiency. On the basis of sensitivity (90%) and specificity (100%), the serum ferritin concentration is more suitable for assessment of iron deficiency than the serum iron concentration, the total iron-binding capacity or the percentual saturation of transferrin. The red cell distribution width (RDW) is the parameter with the highest sensitivity for iron deficiency (94%). An RDW value within the reference interval can be used to exclude iron deficiency in those cases in which the serum ferritin concentration does not accurately reflect the iron stores owing to severe tissue damage, as in inflammation or malignancy. PMID- 2318294 TI - Platelets of patients affected with essential thrombocythemia are abnormal in plasma membrane and adenine nucleotide content. AB - The adenine nucleotides present in distinct cellular compartments of platelets of 27 patients affected with essential thrombocythemia have been measured. In order to quantify granule-bound nucleotides and adenylic cytoplasmic pool, platelets have been stimulated with thrombin or treated with increasing digitonin concentrations, respectively. Among patients, we have identified two groups: 12 patients (Group 1) had normal platelet level of ATP and ADP both in dense granules as well as in cytoplasmic pool. The other patients (Group 2) had granule ATP and ADP significantly lower and ATP/ADP ratio significantly higher than controls. In these patients an increase in hypoxanthine level, derived from metabolic ATP degradation occurring during stimulation, was observed. In addition, in the latter patients an increased resistance of plasma membrane to digitonin was shown, suggesting that membrane fluidity should be reduced owing to a modified cholesterol/phospholipid ratio. PMID- 2318295 TI - Iron bound to low MW ligands: interactions with mitochondria and cytosolic proteins. AB - The iron in the low MW pool of the cell is the precursor of iron in haem and is bound primarily to ATP. This precursor-product relationship suggested that reticulocytes might accumulate ATP-iron if their haem synthesis were blocked. However reticulocytes, treated with succinylacetone or rotenone and taking up iron from transferrin, accumulated iron in nonhaem cytosolic proteins and in mitochondria and not in the low MW pool. This was demonstrated by NMR and also by disrupting the cell with shear stress, separating the cytosol and pellet and fractionating the cytosol with ammonium sulfate. This constancy of the low MW iron pool in the face of blocked haem synthesis could not be explained by saturation of cytosolic ATP or by sluggish exchange of the low MW pool with other compartments. Rather, nonhaem cytosolic proteins and mitochondria appeared to have a higher affinity for iron and to exchange it rapidly with that in the low MW pool. PMID- 2318296 TI - Extramedullary plasmacytomas and solitary plasma cell tumours of bone. AB - We describe clinical features and treatment results in 25 patients with solitary osseous (SOP) and 18 patients with solitary extramedullary plasmacytoma (EMP). 41 patients were treated with high-voltage radiotherapy, median 40 Gy in 20 fractions. Surgery was part of the treatment in 21 and chemotherapy in 5 patients. The median age in both groups was 56 years, with a preponderance of males. Myelomatosis developed in 10 SOP and 2 EMP patients, and this development did not correlate with the presence or absence of an M-component at the time of diagnosis of plasmacytoma. The estimated 5- and 10-y survival was 87% and 76% without a statistical difference between SOP and EMP groups. The patients in the SOP group usually died from myelomatosis while EMP patients died from other causes. PMID- 2318297 TI - Successful chemotherapy for acute myeloid leucaemia in HIV-infected patients. PMID- 2318298 TI - Escavative pulmonary Hodgkin's lymphoma: diagnosis by cutting needle biopsy. PMID- 2318299 TI - Comparative study of immunocytochemical staining versus Giemsa stain for detecting dysmegakaryopoiesis in myelodysplastic syndromes (MDS) AB - 23 patients with myelodysplastic syndromes (MDS) and 8 normal controls were analyzed for dysmegakaryopoiesis (DMP) in the bone marrow by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique and by conventional May-Giemsa staining. In the immunocytochemical study, monoclonal antibody (MoAb) against glycoprotein (GP) IIb/IIIa was utilized to demonstrate megakaryocytic cells. 91% (21/23) of MDS cases were detected as having DMP by APAAP method, while only 52% (12/23) were detectable by Giemsa stain. There were difficulties in recognizing small micromegakaryocytes (micro MKs), designated as type 1 atypical MKs, by Giemsa staining. Furthermore, megakaryoblasts (MKBs) were detectable only by APAAP technique. In 8 normal controls, no type 1 and type 3 atypical MKs (round shaped multinuclear MKs) were observed either by Giemsa staining or by the APAAP method, suggesting that they are a distinctive feature of MDS. These results indicate the necessity of immunocytochemical technique for accurate recognition of DMP in MDS. PMID- 2318300 TI - Bone marrow histopathology in primary myelofibrosis: clinical and haematologic correlations and prognostic evaluation. AB - In 51 patients with primary myelofibrosis the initial bone marrow biopsy findings were evaluated by morphometric methods, correlated with the patients' main clinical and haematologic data and analysed for prognostic significance. The high variability of the marrow features was the most striking finding of the morphologic study. The only remarkable clinico-pathological correlation was that found between the extent of stromal proliferation in the bone marrow and the number of WBC precursors in peripheral blood. Classical bone marrow histologic patterns did not correlate with the main clinical or haematologic data nor did they influence the patients' survival. Finally, collagen fibrosis and abnormal clusters of immature myeloid precursors were the only histologic features showing an unfavourable prognostic significance at the multivariate study. PMID- 2318301 TI - The ribonuclease from an extinct bovid ruminant. AB - The sequence of the ribonuclease from the ancestor of swamp buffalo, river buffalo, and ox, corresponding approximately to Pachyportax latidens, an extinct ruminant known from the fossil record, has been reconstructed using the rule of 'maximum parsimony'. This protein and two sequences that may have been intermediates in the evolution of modern ribonuclease have been constructed in the laboratory by site-directed mutagenesis, and their properties examined. PMID- 2318302 TI - Shape changes of the human red cell studied by aqueous two-phase partition. AB - Aqueous two-phase systems have been used to study the human red cell during metabolically induced shape changes. When the discoid character of the cells was lost in favour of echinocytic forms, the partition increased both in charge sensitive and in charge-insensitive two-phase systems. Reversal of the shape transformation by ATP repletion not only led to shape recovery but also restored the initial partition. Therefore it is apparent that red cells exhibit a shape dependent partition behaviour. As the partition is dependent on surface properties (such as charge and hydrophobicity) of the partitioned material, the results show that the shape changes caused rearrangement of the membrane and thereby exposure of or greater accessibility of binding groups on the cell surface. The similar partition behaviour in the charge-sensitive and charge insensitive phase systems show that the increased partition was caused mainly by increased hydrophobic interactions between the cells and the upper phase. The observed partition behaviour therefore suggests that the echinocytic cells acquire a higher affinity for the upper phase by repacking the lipid bilayer or at least the outer leaflet into a less efficient packed and thus more fluid structure. PMID- 2318303 TI - Evidence for a single butyrylcholinesterase gene in individuals carrying the C5 plasma cholinesterase variant (CHE2). AB - DNA of 3 unrelated individuals carrying the human plasma butyrylcholinesterase C5 variant (CHE2) was isolated from white blood cells. Southern blot patterns of DNA restriction fragments probed with each of the 4 butyrylcholinesterase exons provided evidence that the production of C5 is not directed by a second butyrylcholinesterase gene. This finding supports the suggestion that the C5 variant is a hybrid enzyme resulting from the association of butyrylcholinesterase subunits with a non-cholinesterase protein. PMID- 2318304 TI - Bacterial 'histone-like protein I' (HLP-I) is an outer membrane constituent? AB - The nucleoid-associated 'histone-like protein I' (HLP-I) protein of E. coli was found to be homologous with the cationic 16-kDa outer membrane protein OmpH of Salmonella typhimurium. Deduced from the nucleotide sequence, the HLP-I protein has 91% identical residues with the OmpH protein. Both proteins have very similar cleavable signal sequences. The nucleotide sequence similarity between the corresponding genes hlpA and ompH is 87%. The ompH gene is located in a gene cluster resembling the hlpA-ORF17 region of E. coli which is close to the Ipx genes involved in the biosynthesis of lipopolysaccharides. The localization of the OmpH/HLP-I protein in the cell is discussed. PMID- 2318305 TI - Effects of benzyl alcohol on transferrin and low density lipoprotein receptor mediated endocytosis in leukemic guinea pig B lymphocytes. AB - We demonstrated that benzyl alcohol, a neutral local anesthetic drug, inhibits the uptake and degradation of lowdensity lipoprotein and endocytosis of transferrin receptors of guinea pig leukemic B lymphocytes (L2C). This inhibition is very rapid, concentration dependant and reversible by simple washing. Membrane fluidity of the living cells is also modified. PMID- 2318306 TI - Changes in chromatin chain flexibility during condensation induced by sodium chloride, as evidenced by electric dichroism. AB - The electric linear dichroism of chicken erythrocyte chromatin has been measured as a function of NaCl concentration in the 1-28 mM ionic strength range, using a specially designed Kerr cell with reduced pathlength, and thus, smaller electrode surface. This allowed the determination of the dichroism of compact chromatin in conditions where artifacts due to possible contribution from turbidity are avoided, which was not the case for previous studies in the presence of di- or multivalent cations. The linear dichroism of compact chromatin was found to be positive, as expected from models of the 30-nm fibre in which the linker DNA runs perpendicular to the fibre axis. The dependence of the relaxation times on ionic strength reveals that the process of compaction is first accompanied by an increase in flexibility of the chain followed by a decrease, in the range of 5-10 mM NaCl, and a further decrease above 10 nM NaCl, corresponding to the compaction of the 30 nm fibre. PMID- 2318307 TI - Molecular cloning of cDNA for vitamin D3 25-hydroxylase from rat liver mitochondria. AB - A cDNA clone encoding mitochondrial vitamin D3 25-hydroxylase was isolated from a rat liver cDNA library by the use of specific antibodies to the enzyme. The isolated cDNA clone was 1.9 kbp long and contained a 1599 bp open reading frame encoding 533 amino acid residues. The deduced primary structure contained a presequence typical for mitochondrial enzymes in the N-terminal region. The N terminal sequence of the mature enzyme was determined to be Ala-Ile-Pro-Ala-Ala, which agrees perfectly with a portion of the deduced sequence, establishing the cleavage point of the precursor. PMID- 2318308 TI - Evidence for a molten globule state as a general intermediate in protein folding. AB - The folding of globular proteins occurs through intermediate states whose characterisation provides information about the mechanism of folding. A major class of intermediate states is the compact 'molten globule', whose characteristics have been studied intensively in those conditions in which it is stable (at acid pH, high temperatures and intermediate concentrations of strong denaturants). In studies involving bovine carbonic anhydrase, human alpha-lact albumin, bovine beta-lactoglobulin, yeast phosphoglycerate kinase, beta-lactamase from Staphylococcus aureus and recombinant human interleukin 1 beta, we have demonstrated that a transient intermediate which accumulates during refolding is compact and has the properties of the 'molten globule' state. We show that it is formed within 0.1-0.2 s. These proteins belong to different structural types (beta, alpha + beta and alpha/beta), with and without disulphide bridges and they include proteins with quite different times of complete folding (from seconds to decades of minutes). We propose that the formation of the transient molten globule state occurs early on the pathway of folding of all globular proteins. PMID- 2318309 TI - A gene from pea (Pisum sativum L.) with homology to metallothionein genes. AB - While searching for 'organ-specific' genes in pea (Pisum sativum L.) we have isolated a gene (designated PsMTA) which has an ORF encoding a predicted protein with some similarity to metallothioneins (MTs). The PsMTA transcript is abundant in roots which have not been exposed to elevated concentrations of trace metals. PMID- 2318310 TI - Role of sialic acid residues in crossed immuno-affinoelectrophoresis of alpha 1 proteinase inhibitor. AB - We have investigated the importance of the degree of sialylation when an acute phase glycoprotein, alpha 1-proteinase inhibitor (alpha 1-Pi), was analysed both by affinity chromatography on concanavalin A (Con A)-Sepharose and by crossed immuno-affinoelectrophoresis (CIAE) using Con A in the first dimension. Human alpha 1-Pi was isolated by immunosorption chromatography and then more or less desialylated. On Con A-Sepharose chromatography no significant difference was observed in the percentage of the two fractions (retained or not retained) whatever the degree of desialylation. In contrast by CIAE this degree was largely involved in the separation of the different isoforms obtained in the first dimension. PMID- 2318312 TI - aS,7S-absolute configuration of natural (-)-colchicine and allo-congeners. AB - The aS,7S-absolute configuration of (-)-colchicine (1) and (-)-N-acetylcolchinol methyl ether (3, NCME) suggested on the basis of 1H NMR data and negative Cotton effects at about 260 nm (EtOH) is firmly established by an X-ray analysis of urea 5, a compound derived from 3. Binding of these compounds to tubulin requires an aS-configuration of the biaryl system. PMID- 2318311 TI - Phorbol 12-myristate 13-acetate (PMA) increases the expression of the nerve growth factor (NGF) gene in mouse L-929 fibroblasts. AB - The rise of the NGF mRNA pool which takes place following exposure of L-929 fibroblasts to serum was prevented in the presence of 5 microM K-252a, a compound which inhibits several species of protein kinase activities. To characterize further this phenomenon, L-929 cells growing in a serum-free medium were exposed to cyclic nucleotide analogs, to a divalent cation ionophore or to the phorbol ester PMA. Only this latter compound induced an enhancement of the NGF mRNA pool, suggesting an involvement of protein kinase C in the upregulation of the NGF transcripts. The effects of PMA or serum also require a synthesis of protein since the level of NGF transcripts remained stable in the presence of cycloheximide. PMID- 2318313 TI - Energy transfer via cell-to-cell junctions. Ouabain-resistant cells maintain a membrane potential in ouabain-sensitive cells. AB - Animal cell cooperation has been studied in a mixed cell culture. Membrane potentials of human embryonic cells and hamster BHK-21 cells were recorded by intracellular microelectrodes. The Na+/K(+)-ATPase inhibitor ouabain (1 x 10(-6) M; 2 h) caused strong depolarisation of the human cells in pure culture. The same treatment reduced only slightly the membrane potential in the hamster cells in pure or mixed cultures, as well as in the human cells in mixed culture. The above data can be explained by effective ion fluxes through heterotypic gap junctions in mixed culture. Thus, in the presence of ouabain the Na+/K(+)-ATPase of hamster cells creates transmembrane differences of the electrochemical potential of ions not only in the hamster cells, but in the human cells as well. PMID- 2318314 TI - Identification of the Arg-Gly-Asp sequence in laminin A chain as a latent cell binding site being exposed in fragment P1. AB - A single RGD-containing sequence present within an epidermal growth factor-like repeat of the short arms of laminin is shown by peptide inhibition to block integrin receptors recognizing a latent cell-binding site of laminin. Based on proteolysis data it is proposed that masking occurs by folding of the globular domain IVa over the cell-binding site in the adjacent rod-like structures of laminin A chain. PMID- 2318315 TI - [Itsenko-Cushing disease and pregnancy]. PMID- 2318316 TI - [Actinomycosis of the female genitalia]. PMID- 2318317 TI - [Pneumoconiosis]. PMID- 2318318 TI - [The prevention and treatment of enteritis]. PMID- 2318319 TI - [The differential diagnostic significance of pains in the joints]. PMID- 2318320 TI - [Medicinal plants with hemostatic action]. PMID- 2318321 TI - [The management of pregnancy in women with obesity]. PMID- 2318322 TI - Improved prediction of postovulatory day using temperature recording, endometrial biopsy, and serum progesterone. AB - The use of basal body temperature (BBT) recording and a single progesterone (P) level at the time of the endometrial biopsy in the late luteal phase improved our ability to predict the onset of the next menstrual period (NMP) and determine the postovulatory day (POD) in 124 regularly menstruating infertile women. We determined BBT shift using a microcomputer program, analyzed P levels by radioimmunoassay, and evaluated endometrial biopsies both prospectively (blinded) and retrospectively (with knowledge of the other variables). Serum P levels were within the normal range for the luteal phase and prospective and retrospective histological diagnoses closely agreed (82% within 2 days). The best correlation with the NMP was the BBT shift (r = 0.493) followed by P (r = 0.426) and prospective histologic dating (r = 0.390). Multiple regression analysis confirmed that use of all of the variables markedly improved the ability to estimate the POD (R2 = 0.51). PMID- 2318323 TI - Cytosol progesterone and 17 alpha-hydroxyprogesterone levels and luteinizing hormone and chorionic gonadotropin receptors in human corpora lutea. AB - Cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17-OHP) levels and luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors were measured in 27 corpora lutea and four corpora albicantia. Cytosol P concentrations were highest in corpora lutea (mean +/- SEM, 3.1 +/- 0.8 micrograms/g) during the midluteal phase (days 15 to 19) rather than the early (2.2 +/- 0.8 micrograms/g, days 20 to 25) and late luteal phases (1.8 +/- 0.8 micrograms/g, days 26 to 30). Cytosol 17-OHP concentrations also were 3.3 +/- 0.5, 4.3 +/- 0.6, and 3.3 +/- 1.0 micrograms/g in early, midluteal, and late luteal phases, respectively, and was significantly inversely correlated with occupied LH/hCG receptors in midluteal phase. Corpora albicantia had the lowest P (0.3 +/- 0.05 microgram/g) and 17-OHP (0.9 +/- 0.6 micrograms/g) concentrations. Cytosol P and 17-OHP may therefore reflect the balance between the luteal cell production and secretion, whereas the amount of occupied and unoccupied LH/hCG receptors may partially explain the relationship between LH and P secretion. PMID- 2318324 TI - Psychiatric morbidity in the infertile population: a reconceptualization. AB - The understanding of psychiatric morbidity in the infertile population relies to a great extent upon the instruments used to measure psychopathology. The present study investigated the distinction between psychiatric morbidity and infertility strain reactions in a sample of 104 infertile couples using the SCL-90-R. Some symptoms ordinarily indicative of psychopathology can represent normal side effects or reactions to infertility treatment, thus causing spurious estimates of pathology. Alternately, item analyses revealed a profile of infertility strain reflecting tension, depressive symptoms, worry, and interpersonal alienation frequently occurring among both male and female infertility patients. The concept of infertility strain is suggested as a vehicle for understanding the functioning of infertile patients and to circumvent the stigmatizing effects of psychiatric labels while providing appropriate intervention. PMID- 2318325 TI - A protocol for satisfying the ethical issues raised by oocyte donation: the free, anonymous, and fertile donors. AB - A new protocol was developed to provide participants of our oocyte donation program with oocytes donated by donors who were not financially rewarded, were anonymous, and fertile. Each participant provided an oocyte donor selected among fertile friends or family members. The retrieved oocytes were anonymously exchanged between phenotypically matched donor-recipient pairs. In the first 30 months of activity, we obtained 111 embryos suitable for transfer or cryopreservation from 52 retrievals, and 40 embryo transfers (ETs) were performed. Recipients received oral Estradiol-valerate and vaginal micronized progesterone. Fifteen embryos were transferred in 8 ETs conducted after donor recipient synchronization. This resulted in four pregnancies, all ongoing (ongoing pregnancy rate 50% per transfer). Of the 96 cryopreserved embryos, 82 were thawed for ET, and 45 surviving embryos were transferred in 32 ETs. This resulted in eight pregnancies, with six ongoing or delivered (ongoing pregnancy rate 19% per transfer). The overall ongoing pregnancy rate of 25% per transfer indicates that our approach is a viable method for obtaining donated oocytes while respecting the ethical guidelines that recommended that donation of human gametes should be free, and from anonymous and fertile donors. Furthermore, guaranteeing anonymous oocyte donation had practical importance because, for many volunteer donors, it played a crucial role in their decision to donate. PMID- 2318326 TI - Preclinical abortions: incidence and significance in the Norfolk in vitro fertilization program. AB - Clinical and prognostic significance of preclinical abortions in assisted reproduction is ill defined. Strict diagnostic criteria include a transient and synchronous elevation of serum beta-human chorionic gonadotropin (hCG), estradiol, and progesterone levels 13 days after hCG administration, ending in a bleeding episode no more than 14 days after the missed period. The preclinical abortion study group (54 patients, 178 cycles) was compared with matched control groups A (54 patients, 132 cycles) and B (54 patients, 155 cycles), representing normal term pregnancies and all outcomes, respectively. Control group C included the overall population during the study period. The abortion rate per transfer (preclinical abortion and total miscarriage rates) and total pregnancy wastage in the study group were significantly higher; the ongoing pregnancy rate was significantly lower. Preclinical abortion should be considered as a true reproductive failure with similar implications. PMID- 2318327 TI - Treatment of male sperm autoimmunity by using the gamete intrafallopian transfer procedure with washed spermatozoa. AB - Sixteen couples were diagnosed as having immunological infertility. To detect sperm-bound immunoglobulin (Ig), i.e., IgA, IgG, and IgM antibodies, the direct immunobead test (IBT) was used. In each individual patient, the direct IBT was greater than or equal to 70% positive for either IgA or IgG or both. The indirect IBT was positive for IgA and IgG antibodies in the serum of all the patients. Semen was collected in 15 mL medium (Ham's F10 [Gibco, Grand Island, NY] + 10% whole blood serum) and prepared with the wash and swim-up method. Patients in the study group were treated for their immunological infertility problem by performing the gamete intrafallopian transfer (GIFT) procedure. An ongoing pregnancy was achieved in 7 of the 16 (43%) couples treated with the GIFT procedure with an ongoing pregnancy rate of 24.1% (7 of 29) per cycle. The GIFT procedure appears to be an effective and safe way of treating male immunological infertility. PMID- 2318328 TI - The value of semen analysis and sperm function assays in predicting pregnancy among infertile couples. AB - Over a 2-year period, 227 couples were evaluated by an extended assessment of the male partner's ejaculate. This extended assessment comprised sperm penetration of denuded hamster oocytes, ability of sperm to penetrate synthetic mucus, and the adenosine triphosphate (ATP) content of whole semen. In proportional hazards analysis adjusting for the contribution of clinical and other seminal variables, the sperm penetration assay (SPA) test was a predictor of pregnancy in the subgroup with normal conventional seminal variables (greater than 40 million motile sperm per ejaculate). When the SPA result was 20% or more the probability of pregnancy was 3.7 times higher; the performance of the SPA as a diagnostic test was better in the couples with treated tubal disease than in other diagnostic categories. PMID- 2318329 TI - Variation of movement characteristics with washing and capacitation of spermatozoa. II. Multivariate statistical analysis and prediction of sperm penetrating ability. AB - Fifty semen samples were studied by computer-assisted semen analysis before testing in the sperm penetration assay (SPA). Twenty-one concentration and movement measurements were obtained from each sample on sperm in semen, after washing and swim-up, and again after an 18-hour capacitation period. Discriminant analysis was then used to define a function from these measurements that would classify the SPA results as above or below a 10% penetration rate. A significant function was identified using the following variables: sperm concentration and motility in semen, and mean curvilinear velocity, linearity, and amplitude of lateral head displacement of washed sperm. Movement measurements of capacitated spermatozoa were not useful predictors in this analysis. The overall accuracy of this function for predicting SPA results was 72%. These findings demonstrate that computer-derived measurements of sperm movement provide biologically useful information regarding sperm function, and, in addition, emphasize the importance of multivariate techniques in the analysis and description of human sperm motion. PMID- 2318330 TI - Postoperative adhesion formation after ovarian wedge resection with and without ovarian reconstruction in the rabbit. AB - A rabbit model was used to examine adhesion formation after ovarian wedge resection with and without reapproximation of the ovarian cortex. A wedge resection was completed on one ovary with a scalpel, and the ovarian cortex was reapproximated using microsurgical technique. In the contralateral ovary, a wedge resection was performed using the Nd:YAG laser and the cortex was left to heal by secondary intention. A second laparotomy was performed and the adhesion scores were compared between the two adnexa. In 17 of 19 rabbits, the adhesion score was greater on the side where ovarian reconstruction had been performed. No difference was noted in adhesion scores when, in our preliminary studies presented herein, laser and scalpel wedge resections were both followed by reapproximation of the cortex. These data have ramifications for conservative ovarian surgery performed both at laparotomy and laparoscopy. PMID- 2318331 TI - Clomiphene citrate directly impairs endometrial receptivity in the mouse. AB - Clomiphene citrate (CC) has known antifecundity effects in animal models. To help define the site of action of this effect, we studied the direct effect of CC on endometrial receptivity by transferring embryos to hormonally prepared prepubertal mice. Prepubertal mice were begun on one of four blinded hormonal preparations consisting of two consecutive 3-day periods of daily injections: oil vehicle, oil-progesterone (P), estradiol (E2)-P, or CC-P. Blastocysts, which had not been exposed to CC, were then surgically transferred to these prepubertal recipients. Fourteen days after embryo transfer, implantations and term pregnancies were counted at necropsy. In this model, CC demonstrated no estrogen agonist effect, and had a significant adverse effect on endometrial receptivity. CC appeared to lower fecundity by a direct endometrial effect. PMID- 2318332 TI - In vitro fertilization with spermatozoa from alloplastic spermatocele. AB - This case report describes successful IVF of oocytes of a 22-year-old female with epididymal spermatozoa aspirated from alloplastic spermatocele of the husband presenting with bilateral congenital absence of the vas deferens. Motile spermatozoa were aspirated from the reservoir 3 months after implantation. Abortion occurred 22 days after embryo replacement. PMID- 2318333 TI - Microsurgical fallopian tube transposition. PMID- 2318334 TI - Truth in advertising. PMID- 2318335 TI - The "Holy Grail"--a test for ovulation with metaphysical certainty? PMID- 2318336 TI - Enhancing the partnership: nursing education and practice. PMID- 2318337 TI - Sleeping giant or political power broker--nurses must choose. PMID- 2318338 TI - Nursing shortage update. PMID- 2318339 TI - Differentiation of fiber types in aneural musculature of the prenatal rat hindlimb. AB - The presynaptic neurotoxin, beta-bungarotoxin, was injected into rat fetuses in utero to destroy the innervation of their hindlimb muscles. These injections were made prior to the invasion of motor axons into the muscles and, in some cases, prior to the cleavage of individual muscles. Examination of the lateral motor column of the spinal cord showed a dramatic reduction (greater than 95%) in the number of motoneuron cell bodies. Staining of sections of the hindlimb with silver and with antibodies to neurofilament proteins and to a synaptic vesicle protein indicated that the muscles were aneural. Anti-myosin antibodies applied to sections of the hindlimb revealed that these aneural muscles by the 20th day of gestation had the same types of fibers as were present in normal muscles of the same age. Moreover, fiber types in most muscles showed their characteristic intramuscular distributions. These findings suggest that fiber types can differentiate in the absence of the nervous system. However, some fibers achieved their ultimate fiber type fate without passing through the normal sequence of myosin expressions. Moreover, some slow fibers lost their slow expression, suggesting that the maintenance of the slow differentiation may require innervation. Muscle growth was dramatically affected by the absence of motoneurons; some muscles were decreased in size and others disappeared completely. In muscles which had not degenerated by the time secondary myogenesis normally begins, secondary muscle fibers were generated indicating that the genesis of these fibers is not strictly nerve dependent. Because fiber types differentiate independently of the nervous system, this study suggests that motoneurons selectively innervate fiber types during normal development. PMID- 2318340 TI - Actin and myosin expression during development of cardiac muscle from cultured embryonal carcinoma cells. AB - P19 embryonal carcinoma cells are multipotential stem cells that differentiate into striated muscle as well as some other cell types when aggregated and exposed to dimethyl sulfoxide (DMSO). Immunofluorescence experiments using monospecific antibodies indicated that the majority of muscle cells were mononucleate and contained four myosin isoforms normally found in cardiac muscle; atrial and ventricular myosin heavy chains, ventricular myosin light chain 1, and atrial myosin light chain 2. Northern blot analysis of RNA isolated from differentiating cultures indicated that cardiac actin and skeletal actin mRNAs were expressed at similar levels and with identical kinetics during the differentiation of P19 derived myocytes. These results demonstrate that most of the P19-derived myocytes are of the cardiac type and suggest that they closely resemble the cells of the early embryonic myocardium. PMID- 2318341 TI - Maturation of astrocytes in vitro alters the extent and molecular basis of neurite outgrowth. AB - In the developing mammalian central nervous system astrocytes have been proposed as an important substrate for axon growth. In the adult central nervous system following injury, astrocytes are a major component of the gliotic response which has been proposed to block axon growth. Experimental transplantation studies using cultured astrocytes have suggested that immature but not mature cultured astrocytes have the capacity to support axon outgrowth when transplanted into the adult rodent CNS. These observations suggest that astrocyte maturation is accompanied by changes in the functional capacity of these cells to support axon outgrowth. To determine whether this functional change reflects an intrisic astrocyte property, the extent and molecular bases of neurite outgrowth from embryonic rat cortical and chick retinal neurons on cultures of purified immature and mature astrocytes have been compared in vitro. The rate and extent of neurite outgrowth from both neuronal populations are consistently greater over the surface of immature than over the surface of mature astrocytes. Furthermore, antibodies to NCAM and G4/L1 significantly reduce neurite outgrowth on immature but not mature astrocytes, while antibodies to the integrin B1 receptor reduced outgrowth on both immature and, to a lesser extent, mature astrocytes. These results suggest that in vitro mature astrocytes have a reduced capacity and different molecular bases for supporting neurite outgrowth compared to immature astrocytes and are consistent with the proposal that functional changes during astrocyte maturation may partially contribute to regulating axon growth in the mammalian CNS. PMID- 2318342 TI - Nerve growth cone migration onto Schwann cells involves the calcium-dependent adhesion molecule, N-cadherin. AB - The role of calcium-dependent adhesion molecules in the migration of nerve growth cones onto the top of Schwann cells was probed by examination of sensory growth cone-Schwann cell interactions in medium containing either 1.0 mM Ca2+ or 0.1 mM Ca2+. In the presence of 1.0 mM Ca2+ growth cones rapidly migrated onto Schwann cells, spread, and remained for extended periods. However, in 0.1 mM Ca2+ growth cones still made frequent contacts with Schwann cells, but migration onto the upper cell surface was much reduced. This contrast in growth cone-Schwann cell interactions could be switched rapidly by changing the Ca2+ concentration of the culture medium. Growth cones of retinal neurons showed similar calcium-dependence in their migration onto Schwann cells. Antibodies to the calcium-dependent adhesion molecule, N-cadherin, also blocked growth cone migration onto Schwann cells, but antibodies to another neuronal adhesion molecule, L1, had no effect on growth cone-Schwann cell interactions. Immunocytochemical staining for N-cadherin and L1 indicated that growth cones and Schwann cells have N-cadherin on their surfaces, while L1 is present only on axons and growth cones. These results provide two kinds of evidence that N-cadherin is important in the initial interactions of growth cones and Schwann cells. PMID- 2318343 TI - Isolation of cDNAs encoding four mouse FGF family members and characterization of their expression patterns during embryogenesis. AB - To initiate a study of the role of the fibroblast growth factor (FGF) family in mammalian development, we have isolated cDNAs encoding four mouse FGF family members, aFGF, bFGF, kFGF, and FGF-5. This was achieved by a process that circumvents the use of cDNA libraries: for each family member, a cDNA fragment containing the conserved portion of the coding region was amplified from a pool of embryonic and teratocarcinoma cell cDNAs using the polymerase chain reaction (PCR) and cloned; the remaining coding sequences 5' and 3' to the conserved region were cloned using the RACE method. The cDNA clones obtained were used as probes to analyze the expression of these genes at the RNA level in teratocarcinoma cells and embryos at 10.5 to 17.5 days of gestation. Fgfk appears to be specific to undifferentiated teratocarcinoma stem cells. Fgf5 transcripts were detected at every stage and in every tissue tested, but showed a dramatic 15 fold increase in abundance as teratocarcinoma stem cells differentiated to simple embryoid bodies. Fgfb expression showed the greatest tissue-specific variability in abundance, with the highest levels detected in the developing limbs and tail. Fgfa showed the least variable pattern of expression, with transcripts detected at roughly equivalent levels in almost all samples analyzed. On the basis of these data we speculate on some possible roles that the different FGF family members may play in the developing embryo. PMID- 2318344 TI - Cloned interstitial stem cells grow as contiguous patches in hydra. AB - The migration of interstitial cells was analyzed during the growth of stem cell clones in vivo. The spatial distribution of cloned cells was analyzed at a time by which extensive migration of interstitial cells could have occurred. All interstitial cell clones were found to form large contiguous patches of cells. The results indicate that there is little migration of large interstitial cells in undisturbed tissue during normal growth. This finding is surprising since numerous grafting experiments have shown extensive migration of these cells. The implications of finding nonrandomly distributed stem cells are discussed. PMID- 2318345 TI - Effects of omega-3 fish oils on plasma lipids, lipoprotein composition, and postheparin lipoprotein lipase in women with IDDM. AB - Because the apparent reduction in cardiovascular risk noted in nondiabetic populations that ingest diets rich in marine lipids containing omega-3 fatty acids is believed to result in part from their capacity to modify the composition and physicochemical behavior of lipoproteins, we sought to determine whether dietary supplementation with marine lipids might favorably affect lipoprotein composition in insulin-dependent diabetes mellitus (IDDM). Eight normolipidemic IDDM women (mean +/- SD age 29.8 +/- 4.7 yr) were studied before and 3 mo after receiving a marine-lipid concentrate (Super-EPA) containing 6 g omega-3 fatty acids and a total of 12 mg of cholesterol daily. Weight, insulin requirements, and glycosylated hemoglobin remained stable. After treatment, mean +/- SD plasma triglyceride (TG) levels fell (before, 81.7 +/- 22 mg/dl; after, 69.19 +/- 17; P less than 0.025). High-density lipoprotein2 (HDL2) cholesterol (before, 10.98 +/- 5.45 mg/dl; after, 18.43 +/- 7.93; P less than 0.01), its major apolipoprotein A I (apoAI), and the major phospholipids (sphingomyelin and lecithin) all rose significantly. ApoB and plasma and low-density lipoprotein cholesterol levels and HDL3 composition were unchanged. Postheparin hepatic and lipoprotein lipase activities were unaffected by marine lipids. These data indicate that women with IDDM experience apparently beneficial effects on TG and HDL2 from dietary supplementation with omega-3 fatty acids administered in a low-cholesterol containing oil without adversely affecting overall diabetes management. If these changes in lipoprotein concentration and composition prove to have antiatherogenic consequences and are free of long-term toxicity, these agents may have a role in the therapy of IDDM patients. PMID- 2318346 TI - Effect of diet on incidence of diabetes in nonobese diabetic mice. AB - Nonobese diabetic/Lt mice exhibit a diabetes incidence greater than 70% in females at 30 wk of age. In studies designed to see whether increased dietary carbohydrate, fat, or protein influenced the severity or age at onset of the syndrome, we fed semipurified AIN-76 diet adulterated with increased amounts of these ingredients. Surprisingly, all AIN-76-based diets greatly reduced the expected incidence of diabetes at 30 wk. In addition, a hypoallergenic infant formula, Pregestimil, containing casein hydrolysate in place of protein, completely prevented diabetes up to 1 yr of age. To assess how dietary components might modulate the diabetes incidence, we adulterated standard AIN-76 diet with skim milk, gluten, brewer's yeast, or a natural-ingredient rodent open-formula mouse diet (Old Guilford 96 [OG96]. No increase in diabetes incidence was seen with skim milk (10%) or wheat gluten (10%), whereas brewer's yeast (10%) and OG96 (25%) added to AIN-76 increased the incidence compared to mice fed OG96 only. The diabetogenic factor or factors in OG96 could be extracted by chloroform plus methanol (2:1), leaving little activity in the residue. We conclude that diet is a critical factor in diabetes development and that unknown chloroform-methanol soluble substances in natural-ingredient chow not found in semipurified diets can enhance the development of diabetes in genetically susceptible mice. PMID- 2318347 TI - Regional brain glucose metabolism and blood flow in streptozocin-induced diabetic rats. AB - Brain regional glucose metabolism and regional blood flow were measured from autoradiographs by the uptake of [3H]-2-deoxy-D-glucose and [14C]iodoantipyrine in streptozocin-induced diabetic (STZ-D) rats. After 2 days of diabetes, glucose metabolism in the neocortex, basal ganglia, and white matter increased by 34, 37, and 8%, respectively, whereas blood flow was unchanged. After 4 mo, glucose metabolism in the same three regions was decreased by 32, 43, and 60%. This reduction was paralleled by a statistically nonsignificant reduction in blood flow in neocortex and basal ganglia. It is suggested that the decrease of brain glucose metabolism in STZ-D reflects increased ketone body oxidation and reduction of electrochemical work. PMID- 2318348 TI - Decreased inner cell mass proportion in blastocysts from diabetic rats. AB - Late morulae and blastocysts were recovered from streptozocin-induced diabetic pregnant rats and individually examined for numbers of inner cell mass (ICM) cells and trophectoderm (TE) cells. Compared with embryos collected from control rats, exposure to maternal diabetes significantly decreased mean ICM cell number of blastocysts recovered on day 5 of gestation, but the TE population of these embryos remained unaffected. The mean ICM proportion was therefore significantly lower than that of control embryos. These differences were not observed between the two groups of morulae collected on day 5, suggesting that the distinctive susceptibility of the ICM was expressed after blastocyst formation. On day 6, a significant inhibitory effect of diabetes was observed on the growth of both ICM and TE cells, but because the reduction was more severe in the ICM than in the TE, the mean ICM proportion of these blastocysts was again significantly lower than in control embryos. A linear quadratic relationship was obtained between the numbers of ICM cells of individual blastocysts and their respective numbers of TE cells in each of the two experimental groups. However, the slope of the curve was slower in the diabetic group than the control group. The disturbed ICM cell growth in the blastocysts from diabetic rats was found to be associated with a significantly increased incidence of cell death predominantly located in the ICM. Because it is known that excessive reduction of the ICM is incompatible with normal embryogenesis after implantation, our results suggest that the differential sensitivity of ICM and TE cells in preimplantation blastocysts may contribute to the pattern of postimplantation defects described in diabetic pregnancies. PMID- 2318349 TI - Assessing the efficacy of azaprophen and physostigmine as a pretreatment for soman-induced incapacitation in guinea pigs by response-surface modeling. AB - Physostigmine (PHY) has the advantage over pyridostigmine of minimizing OP induced incapacitation because it penetrates into the CNS. However, physostigmine is behaviorally toxic at relatively low concentrations. It is anticipated that this could be offset by a cholinolytic to prevent behavioral deficit due to the carbamate pretreatment alone. The therapeutic efficacy of physostigmine/azaprophen pretreatment therapy was evaluated in soman-challenged guinea pigs. Response surface methodology was employed to describe the relationship of the pretreatment combination with duration of incapacitation. The significance of the combination relative to PHY alone was evaluated in addition to dose combinations that yield optimal time to recovery. Analysis of the fitted response surface indicated that combination pretreatment with these compounds significantly reduces the time to recovery after soman challenge versus pretreatment with PHY alone. PMID- 2318350 TI - Ethylene dichloride: the influence of disulfiram or ethanol on oncogenicity, metabolism, and DNA covalent binding in rats. AB - Male and female Sprague-Dawley rats were exposed to 50 ppm ethylene dichloride (EDC) for 7 hr/day, 5 days/week, for 2 years by inhalation. Additional rats were exposed to 50 ppm EDC either with 0.05% disulfiram in the diet or with 5% ethanol in the drinking water. Histopathologic lesions related to the combination of inhaled EDC and dietary disulfiram were observed in the liver, mammary, and testicular tissues of rats. This combined exposure resulted in a significant increase in the incidence of intrahepatic bile duct cholangiomas in both male and female rats. Male rats exposed to both EDC and disulfiram also had an increased incidence of subcutaneous fibromas, neoplastic nodules, and interstitial cell tumors in the testes. The female rats exposed to EDC and disulfiram also had a higher incidence of mammary adenocarcinomas. No significant increase in the number of any tumor type was observed in rats exposed to only EDC, disulfiram, or ethanol. Similarly, no significant increase in the number of tumors was observed in rats exposed to inhaled EDC and ethanol in water. At the end of the 2-year period animals from each group were evaluated for EDC metabolism and DNA binding. Blood levels of EDC at the end of a 7-hr exposure period were significantly higher for rats exposed to both EDC and disulfiram than for rats exposed to EDC alone. In addition, the elimination of a single oral dose of radiolabeled EDC was affected. The urinary excretion of 14C from control rats was 47 to 55% of the administered dose with 28 to 30% detected as unchanged EDC in the breath. In disulfiram-treated rats, only 35 to 36% of the administered 14C was eliminated in the urine with 41 to 55% as unchanged EDC in the breath. The urinary metabolite HPLC profile was qualitatively unchanged by long-term EDC, disulfiram, or ethanol treatment, either alone or in combination, and consisted primarily of thiodiglycolic acid, thiodiglycolic acid sulfoxide, and chloroacetic acid. PMID- 2318351 TI - Arsenic distribution in rabbits after Lewisite administration and treatment with British anti-Lewisite (BAL). AB - The standard treatment of Lewisite (dichloro(2-chlorovinyl)arsine) poisoning is by chelation with BAL (British anti-Lewisite, dimercaptopropanol). The present study investigated the effect of BAL treatment on the distribution of arsenic after Lewisite administration. Lewisite was administered subcutaneously at the LD10 and LD40 of the compound. Without BAL treatment arsenic was eliminated with a half-life in blood of between 55 and 75 hr and a blood clearance of 120 ml/hr/kg. Arsenic had a large volume of distribution of several liters per kilogram, indicating extensive distribution in tissues. The highest tissue concentrations, more than seven times blood concentrations, were found in the liver, lung, and kidneys. These organs maintained an approximately constant concentration ratio with blood during the sampling period. Concentrations in tissues with a blood-to-tissue barrier, such as the brain and the spinal cord, rose between 4 and 96 hr while blood concentrations declined more than fourfold over the same time period. BAL treatment by four equal, maximally tolerated doses over 12 hr substantially reduced arsenic concentrations in blood and tissues. For example, at 24 hr the concentrations in brain and liver (target organs for arsenic toxicity) were reduced by 65 to 89% over the range of Lewisite doses administered. The total exposure of brain and spinal cord was reduced by more than two-thirds by BAL treatment. Further, the blood clearance of arsenic was increased. BAL treatment enhanced the elimination of arsenic in two ways: by decreasing the tissue-to-blood partitioning which mobilizes arsenic into the blood stream, and by increasing the clearance of arsenic. PMID- 2318352 TI - 4,4'-Methylene-bis(2-chloroaniline) (MOCA): comparison of macromolecular adduct formation after oral or dermal administration in the rat. AB - The macromolecular binding of 4,4'-methylenebis(2-chloroaniline) (MOCA), a suspect human carcinogen, was studied in the adult male Sprague-Dawley rat after both oral and dermal administration. Rats were euthanized 1, 3, 7, 10, 14, and 29 days after a single 281 mumol/kg body wt dose of [14C]MOCA (oral, 213 muCi/kg; dermal, 904 muCi/kg). DNA from various tissues and hemoglobin were isolated for determination of the time course of MOCA macromolecular binding. After oral administration adduct formation was rapid with maximum levels appearing at 24 hr. The 24-hr covalent binding associated with the globin was 7.84 pmol/mg globin (t1/2 = 14.3 days). More extensive 24-hr covalent binding was detected for liver DNA with 49.11 pmol/mg DNA (t1/2 = 11.1 days). After dermal administration of MOCA the major portion of the dose, 86.2%, remained at the application site throughout the study. For these rats the 24-hr covalent binding determined for liver DNA was 0.38 pmol/mg DNA (t1/2 = 15.6 days). Although lower levels were detected after dermal application, similar stability of MOCA-DNA adducts indicates that quantification of such MOCA adducts may be useful for the long term industrial biomonitoring of MOCA exposure and for the evaluation of human DNA-MOCA adduct formation, a lesion thought to be associated with the production of cancer. PMID- 2318353 TI - Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats. AB - These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24, 32, or 48 mg/kg of m-DNB and killed at 14 days post-treatment. Mortality and neurotoxicity were observed at 48 mg/kg, but only in the older animals. Epididymis weight, testicular sperm head counts, cauda sperm reserves, and sperm morphology were affected at 16 and 24 mg/kg and higher in the older and younger animals, respectively. Testis weight and sperm motility were affected at 24 mg/kg and higher in both age groups. Histologic changes included maturation depletion of mid and late spermatids at 16 mg/kg and higher, atrophy of a few to many seminiferous tubules at 24 mg/kg and higher, and immature germ cells in the epididymis. The movement and/or mixing of luminal elements in the epididymis appeared to be influenced by severe testicular effects. In separate groups given only the 48 mg/kg dosage, fertilizing ability was lost by 5-6 weeks post-treatment and several animals failed to recover in 5 months. In the breeder males, minimal to extensive degrees of seminiferous tubule atrophy and sloughed germ cells in the epididymis were still present after 175 days. The studies indicated that the lowest dosage to produce reproductive changes was 16 mg/kg with a no-effect level of 8 mg/kg. A few animals suffered protracted or permanent reproductive damage. Since the older animals were more susceptible to both the general and the reproductive toxicity of m-DNB, the less severe reproductive changes in the younger animals cannot be attributed solely to maturational differences in the testis. PMID- 2318354 TI - Dermal absorption of organic chemical vapors in rats and humans. AB - Quantitation of chemical vapor penetration through skin is necessary for assessment of health hazards involved in some occupational environments. Information on penetration of vapors through human skin is minimal because human exposures are not sanctioned. We have investigated the whole-body dermal penetration of styrene, xylene, toluene, perchloroethylene, benzene, halothane, hexane, and isoflurane in rats and compared the permeability constants with available human studies on vapor penetration. Rats with closely clipped fur were exposed to organic chemical vapors (3000 to 60,000 ppm) while breathing fresh air through a latex mask. Blood concentrations taken during the 4-hr exposures were determined by sampling through indwelling jugular cannulas. A physiologically based pharmacokinetic model was used to predict permeability constants consistent with the experimental blood concentrations. Permeability constants (cm/hr) were estimated by a least-square optimization and ranged from 1.75 cm/hr for styrene to 0.03 cm/hr for isoflurane. Rat permeability constants were uniformly two to four times greater when compared to the human constants which were calculated from the literature. These results indicate that organic vapor permeability constants in rats are a conservative estimate of organic vapor permeability constants in humans and that the consistent differences in permeability constants between these two species may be due to physiological differences in the skin. PMID- 2318355 TI - Modulation of respiratory burst activity and mitogenic response of human peripheral blood mononuclear cells and murine splenocytes and peritoneal cells by malathion. AB - Previous studies showed that acute administration of noncholinergic doses of malathion in vivo elevated the humoral immune and mitogenic responses but did not alter the generation of the cytotoxic T lymphocyte (CTL) response to alloantigen of splenocytes from treated mice. However, in vitro exposure to malathion suppressed the generation of a CTL response. In this study, the effects of in vivo and in vitro (with and without an NADPH-regenerating liver enzyme system) exposure to malathion on the mitogenic responses of murine splenocytes or respiratory burst activity of peritoneal cells were examined. The effect of in vitro exposure to malathion on the ability of human peripheral blood mononuclear cells (PBMC) to perform these functions was also examined. In vivo exposure to malathion significantly elevated proliferative responses of murine splenocytes to mitogens. Cell separation and reconstitution studies indicated that adherent splenocytes from treated mice could elevate the proliferative responses of nonadherent splenocytes from control mice. Alternatively, in vitro exposure of murine splenocytes or human PBMC to malathion or malathion metabolized by a liver enzyme system suppressed or did not change, respectively, the proliferative responses to mitogens. In addition, cell separation and reconstitution experiments indicated that in vitro exposure to malathion affected nonadherent splenocytes and PBMC. In vivo exposure to malathion also elevated the production of hydrogen peroxide, following stimulation with phorbol myristate acetate, by murine peritoneal cells. In vivo exposure of murine peritoneal cells to malathion suppressed or elevated the respiratory burst activity following exposure to malathion or malathion metabolized by a liver enzyme system, respectively. Exposure of human PBMC to metabolized malathion in vitro enhanced their ability to produce hydrogen peroxide. PMID- 2318356 TI - Toxicologic studies on a novel antineoplastic bis-Mannich base, derived from a conjugated styryl ketone. AB - A new bis-Mannich base (NC758) derived from a conjugated styryl ketone has demonstrated activities against human and animal tumors, both in vitro and as xenografts in athymic mice. The present study examined the toxicity of this candidate anticancer drug, when administered intraperitoneally by undertaking LD50, acute dose-response and time-response toxicity studies using CD-1 mice following OECD guidelines. An LD50 of 46.9 +/- 1.4 mg/kg (males) and 65.2 +/- 1.5 mg/kg (females) was calculated using the moving averages method. Signs of toxicity included diarrhea, piloerection, and coma. Gross pathologic findings consisted of an acute fibrinous peritonitis in animals surviving 24 hr or more before death. The acute dose-response study revealed anorexia in mice 24 hr after receiving 25 mg/kg NC758 or more, lasting up to 72 hr in the 50 mg/kg treated group. Neutrophils were significantly elevated in the 25 and 50 mg/kg groups in conjunction with the observed acute peritonitis. Treatment (p = 0.0001), sex (p = 0.0008), and treatment/sex interaction (p = 0.0001) effects were seen in the myeloid-erythroid ratio (MER) of bone marrow. Pathologic changes included thymic necrosis (in all treated mice) and intestinal villous atrophy (in mice treated with 25 and 50 mg/kg). In time-response studies, pathological changes disappeared after 14 days, except for the MER which remained abnormal in males. It was concluded that NC758 was corrosive; hence future studies should utilize the intravenous route, or be given intraperitoneally as divided doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318357 TI - Chronic toxicity of dichloroacetate: possible relation to thiamine deficiency in rats. AB - The chronic use of dichloroacetate (DCA) for diabetes mellitus or hyperlipoproteinemias has been compromised by neurologic and other forms of toxicity. DCA is metabolized to glyoxylate, which is converted to oxalate and, in the presence of adequate thiamine levels, to other metabolites. DCA stimulates the thiamine-dependent enzymes pyruvate dehydrogenase and alpha-ketoacid dehydrogenase. We postulated that the neurotoxicity from chronic DCA administration could result from depletion of body thiamine stores and abnormal metabolism of oxalate, a known neurotoxin. For 7 weeks, rats were fed ad lib. Purina chow and water or chow plus sodium DCA (50 mg/kg or 1.1 g/kg) in water. A portion of the DCA-treated animals also received intraperitoneal injections of 600 micrograms thiamine three times weekly or 600 micrograms thiamine daily by mouth. Thiamine status was assessed by determining red cell transketolase activity and, in a blinded manner, by recording the development of clinical signs known to be associated with thiamine deficiency. At the 50 mg/kg dose, chronic administration of DCA showed no clinical toxicity or effect on transketolase activity. At the 1.1 g/kg dose, however, DCA markedly increased the frequency and severity of toxicity and decreased transketolase activity 25%, compared to controls. Coadministration of thiamine substantially reduced evidence of thiamine deficiency and normalized transketolase activity. Inhibition of transketolase by DCA in vivo was not due to a direct action on the enzyme, however, since DCA, glyoxylate, or oxalate had no appreciable effects on transketolase activity in vitro. After 7 weeks, plasma DCA concentrations were similar in rats receiving DCA alone or DCA plus thiamine, while urinary oxalate was 86% above control in DCA-treated rats but only 28% above control in DCA plus thiamine-treated animals. No light microscopic changes were seen in peripheral nerve, lens, testis, or kidney morphology in either DCA-treated group, nor was there disruption of normal sperm production in the DCA-treated group. We conclude that stimulation by DCA of thiamine-requiring enzymes may lead to depletion of total body thiamine stores and to both a fall in transketolase activity and an increase in oxalate accumulation in vivo. DCA neurotoxicity may thus be due, at least in part, to thiamine deficiency and may be preventable with thiamine treatment. PMID- 2318358 TI - Subchronic toxicity of tetrahydrofuran vapors in rats and mice. AB - Tetrahydrofuran (THF), a four-carbon, cyclic ether, is widely used as an industrial solvent. Groups of 10 rats and mice of each sex were administered THF vapor by whole body inhalation for 13 weeks at exposure concentrations of 0, 66, 200, 600, 1800, and 5000 ppm. The body weights and survival were not affected by THF exposure, except in male mice at 5000 ppm concentration which had reduced weight and three deaths. Clinical signs of central nervous system (CNS) toxicity were observed in both rats and mice at high dose levels. Rats of both sexes exposed to 5000 ppm were ataxic and mice exposed to 1800 or 5000 ppm appeared to be in a state of narcosis. There were no exposure-related gross necropsy findings in rats or mice. At 5000 ppm, decreases in thymic and spleen weights in rats and mice of both sexes and increases in liver weights in both sexes of mice and in female rats were observed. A minimal to mild centrilobular hepatocytomegaly occurred in male and female mice exposed to 5000 ppm THF. Atrophy of the uterus and degeneration of the X zone in the adrenal cortex occurred in female mice exposed to 5000 ppm THF. THF exposure of rats was associated with minimal to mild acanthosis and inflammation in the forestomach. In conclusion, these studies suggest that THF, like other commonly used organic solvents, causes narcosis in rats and mice. Although minimal exposure-related effects were seen in the liver of both species, morphologic changes were present only in mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318359 TI - Changes in hepatocyte ploidy in response to chromium, analyzed by computer assisted microscopy. AB - BDF1 mice were given single injections of sodium dichromate (25 mg/kg) on an acute (6 hr to 7 days) or intermediate (2-4 weeks) basis, or multiple injections (12.5 mg/kg) on a chronic (4.5 months) basis. Observed hepatic changes included programmed cell death (apoptosis) in the periportal region with acute exposure and fusion of liver lobes with chronic exposure. Response to chromate exposure was measured by change in hepatocyte nuclear ploidy state (e.g., the proportion of diploid, tetraploid, and octaploid nuclei) based on computer-assisted imaging from histological sections. The computer-assisted imaging system used in this study was superior to traditional methods because it (1) allows rapid ploidy determinations from histological material and (2) can be used to collect regional information. Regional differences in ploidy were seen to occur in a consistent fashion among both control and treated animals. Nuclei adjacent to the portal triad had the lowest ploidy value (highest proportion of diploid nuclei), an intermediate value was found adjacent to the central vein, and the highest ploidy was found in the midzone. These three ploidy-based zones roughly correspond to the three functional zones of A. M. Rappaport (1973, Microvasc. Res. 6, 212-228) and W. H. Lamers et al. W. H. Lamers, A. Hilberts, E. Furt, J. Smith, G. N. Jonges, J. F. Van Noorden, J. W. G. Janzen, R. Charles, and A. F. M. Moorman, 1989, Hepatology, 10, 72-76. Temporal changes in ploidy were seen among control animals (all zones), with young animals (56 days) displaying relatively low ploidy values compared to older animals (184 days). Chromate exposure caused increased ploidy (all zones) among animals treated on an acute basis (the youngest animals). Chromate had no apparent effect on ploidy among animals treated for longer periods of time, probably because of age-related factors. PMID- 2318360 TI - Some novel inhibitors of platelet aggregation: acute toxicity in mice and its relationship to in vitro efficacy and toxicity. II. Nipecotoylaminoalkane and nipecotoylpiperazine congeners. AB - Four closely related nipecotoyl congeners are employed as molecular probes to evaluate the effects of systematic molecular changes upon lethal potency of the compounds. The in vivo toxicities, effected by changes in molecular structure, are compared to their in vitro concentrations inhibiting ADP-induced aggregation and epinephrine-induced primary aggregation of human blood platelets and their toxicities to mouse fibroblasts (L-929 cells) in culture. To assist in the selection of compounds which offer the greatest promise as therapeutic agents for further evaluation and to guide future development of optimal molecular structures, a ratio of acute ip LD50 (mumol/kg) [Tm] to concentration inhibiting 50% ADP-induced platelet aggregation (mumol/liter) [A] is calculated for each compound. These ratios range from 2.41 to 24.92 for the four compounds included in this study. PMID- 2318361 TI - Toxicity and metabolism of trimethylarsine in mice and hamsters. AB - Trimethylarsine (TM-As) proved to be an arsenic compound of low toxicity, with a po LD50 of 7870 mg/kg in mice. A single po dose of 10 mg/kg of TM-As caused no hemolysis, but a single po dose of 750 mg/kg induced mild, transient hemolysis in hamsters. TM-As was very rapidly eliminated into the urine, with a biological half-life of 3.7 hr. TM-As was oxidized in vivo to form trimethylarsine oxide (TMAO) and excreted as such into the urine. TM-As was never demethylated in vivo. A mechanism was demonstrated by which a part of TM-As was eliminated directly into the expired air. We drew a conclusion that TM-As is far less an toxic than arsine, most probably due to its in vivo conversion to TMAO. PMID- 2318362 TI - Computer-automated structure evaluation (CASE) of retinoids in teratogenesis bioassays. AB - The potential usefulness of the retinoids, a large group of synthetic compounds chemically and structurally related to vitamin A, in the treatment of severe dermatologic diseases and in the prophylaxis and therapy against cancer is severely limited because of their potential teratogenicity. CASE analysis of published retinoid data from the hamster teratogenicity assay and the limb bud "spot" culture system has targeted the hydrophobic region of the retinoids as having the greatest effect on the range of potencies studied. In addition, log p's (as calculated by the CASE program) below a certain value appear to unilaterally result in nonteratogenic retinoids in the in vivo hamster assay system. PMID- 2318364 TI - Health for all: ten years and some distance to go. PMID- 2318363 TI - Metal homeostasis and metallothionein induction in rainbow trout hepatocytes exposed to cadmium. AB - This study was undertaken to investigate the cellular effects of Cd and metallothionein (MT) metabolism using a primary cell culture system composed of isolated rainbow trout (Salmo gairdneri) hepatocytes. The cells were exposed to 89 nM Cd for 0, 5, 12, 20, 25, 30, 35, and 40 hr at 15 degrees C. The concentration of Cd used did not cause significant cell damage, as estimated by lactate dehydrogenase (LDH) release into the extracellular medium. However, the presence of the metal led to increased cellular levels of calcium within the first 12 hr of incubation. Later, these returned to control values and remained as such for the rest of the examination period. A transient increase in intracellular copper and zinc also occurred during the initial incubation period. In parallel, the hepatocytes were found to accumulate appreciable quantities of Cd, a significant proportion of which were detected in the cytosol. Distribution profiles of cytosolic Cd obtained through Sephadex G-75 chromatography showed that the metal was associated mainly with the high-molecular-weight (HMW) and middle-molecular-weight (MMW) protein fractions. At t = 12 hr, there was a maximum in the proportion of Cd in the MMW fractions, which was accompanied by a decrease in the proportion of Cu in the same fractions. At this time, cellular MT exhibited the highest levels. MMW fractions were further resolved using anion exchange chromatography. Although Cd was present in the peaks corresponding to MT, the data indicated that these peaks also contained detectable amounts of Cu and Zn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318365 TI - Attitudes to the training of general medical practitioners in Nigeria. AB - Nigeria has pioneered a vocational training programme for general medical practitioners. The first major evaluation and review of the curriculum took place in July 1988 when over 50 trainees, supervisors and faculty board members attended a conference at Ibadan University. The opportunity was taken to assess by questionnaire the views of the participants on a range of issues related to health care in Nigeria and of the training and supervision of general medical practitioners. Sixty-six per cent of potential respondents provided completed questionnaires. A large proportion of respondents felt the need for some revisions in the curriculum and for a greater emphasis on small group training. The results indicated scepticism about the role of high technology medicine and private medical practice in meeting the health needs of Nigerians. There were some differences between the trainees and their supervisors and faculty board members in the responses obtained. The programme in Nigeria and the attitudes of those taking part demonstrate a vigorous and visionary approach to health care. It is hoped that this experience will be a useful and important example of what can be achieved in a country with potential for development. PMID- 2318366 TI - Health for all in Nicaragua. AB - The state of health care in Nicaragua can be attributed in part to the interaction between 'revolutionary' and 'counter revolutionary' forces. Since 1979 development of primary health care has been rapid and ambitious. Nicaragua's early successes in the pursuit of 'Health for all by the year 2000' have been widely reported and rightly acclaimed. Since 1983, however, these advances have been difficult to maintain, leading to stasis and deterioration in the health system. The contribution of various factors to the current health status of Nicaragua is examined. PMID- 2318367 TI - Dental health of Spanish children: an investigation in primary care. AB - The oral hygiene of patients between seven and 14 years old from a health centre in Toledo was studied through case-finding from March to December 1987. A total of 304 interviews were held; bad dental care (frequency of teeth brushing with fluoride toothpaste less than once per day and/or daily consumption of chocolate and sweets) was found in 83%, and caries were diagnosed through inspection in 92% of the patients. Seventy three per cent reported washing their teeth only occasionally or never; 40% consumed sweets daily; 53% had never visited the dentist; and 50% had not received preventive care for dental disease. These results contrast with those from the United Kingdom and other developed countries, indicating a precarious state of dental health in Spain, a fact which should be taken into account by the Spanish health organization when comparing the health levels between different countries. PMID- 2318368 TI - Patient-centredness in the consultation. 2: Does it really make a difference? AB - The major purpose of this study was to test the hypothesis that patient centredness in the consultation was associated with improved patient outcomes. Patient-centred care was defined as care in which the doctor responded to the patient in such a way as to allow the patient to express all of his or her reasons for coming, including: symptoms, thoughts, feelings and expectations. The study took place in the offices of six family doctors. All consultations were audiotaped and the patients completed a questionnaire and two structured interviews with the investigator: one immediately following the consultation and the other two weeks later. Patient-centredness was found to be associated with the doctor having ascertained the patient's reasons for coming and with resolution of the patient's concerns. It was also associated with the patient feeling understood and resolution of the patient's symptoms until confounding variables were controlled. The results of the multivariate analysis suggested that the impact of a patient-centred approach may be part of a package of care, consisting of a doctor whose overall practice allows for the development of personal relationships with patients over time through continuity of care. PMID- 2318369 TI - Working in the Third World: a guide for the family doctor. PMID- 2318370 TI - Handling of confidentiality in general practice: a survey among general practitioners in The Netherlands. AB - This paper describes the results of a study of the handling of confidentiality by general practitioners. A sample of 272 general practitioners in the eastern part of the Netherlands was interviewed. The general practitioners were presented with 10 cases involving confidentiality and were asked what course of action they would pursue. Twenty-eight per cent of the general practitioners would never disclose information to others without the patient's consent, while 14% would disclose information to other physicians, members of non-medical professions and relatives. The largest proportion (38%) would disclose information only to other physicians. General practitioners were less likely to divulge information if they were: younger, female or practising in group practices. In particular, general practitioners who involved patients in decision making were less likely to disclose information to third parties. A plea is made for more education about confidentiality in the medical curriculum. PMID- 2318371 TI - Patients' needs after radiotherapy, the role of the general practitioner. AB - This study assessed the physical and psychosocial sequelae of radical radiotherapy among patients with bladder or prostate cancer and investigated the support received from community health services. When interviewed two months after treatment, over half reported that they had experienced several physical side-effects as well as curtailment of social and everyday activities. Such side effects were still being experienced by up to half the patients at the time of interview. Seventy-one per cent were unprepared for the duration and type of such effects. Most had seen their general practitioner in connection with their side effects and 76% felt that this contact had been helpful. Patients appreciated the willingness to spend time listening to their concerns and explaining side effects, as well as accessibility and flexibility which made it easy to obtain advice and support. Patients who expressed dissatisfaction with their general practitioner all felt that they should have been visited at home. The study suggests that general practitioners can play a valuable role in meeting patients' needs after radiotherapy. PMID- 2318372 TI - Non-pharmacological treatment of hypertension: differences between health centres in patients' blood pressure and success at withdrawal from drugs. AB - Four hundred patients from eight health centres were recruited for this two-year study on the possibility of replacing antihypertensive drugs by non pharmacological therapy. This consisted of monthly check-ups and blood pressure measurements at home by the patients plus advice about changes of lifestyle--salt restriction, weight reduction, physical activity, and reduction of alcohol and tobacco. The non-pharmacological treatment was effective and 44% had discontinued drugs after two years without any increase in diastolic blood pressure. Twenty five per cent reduced their weight by 4% or more. There were no changes in sodium or potassium output. Thirty-five per cent increased their physical activity and 20% decreased it. When the results for each health centre were compared, striking differences in hypertensive characteristics of patients and the outcome of antihypertensive drug treatment were found. In one health centre 69% of patients were not taking drugs after two years. In some health centres the non pharmacological treatment was quite successful, but in others the attempt failed. A prerequisite for successful use of pharmacological treatment is that the problem of non-compliance should be solved. PMID- 2318373 TI - Family planning in rural Africa: can it work? AB - High fertility is the major demographic problem presently affecting rural Kenya. Chogoria Hospital has attempted to provide a community based family planning service to address this issue. This paper describes the intervention used and analyses the current contraceptive practice in the area. It is concluded that community based distribution of family planning commodities may be associated with a marked decrease in fertility rate and family size within a relatively short period. Family planning initiatives in Africa may be remarkably cost effective interventions in the development of a nation and be associated with well spaced and healthy children. PMID- 2318375 TI - Supervised withdrawal of long-term digoxin therapy. AB - All 32 patients treated with digoxin for over three months in one practice population had treatment withdrawn under supervision to assess its continued requirement. In 18 instances (56%) digoxin proved necessary and was restarted to correct clinical deterioration, while in 14 instances (44%) it was successfully discontinued. Successful withdrawal was more frequently achieved in those with sinus rhythm (91% of 14 patients) than in atrial fibrillation (19% of 21 patients). Where digoxin was required dosage increases were necessary to achieve optimum clinical control. Adherence to a strict protocol allows unnecessary therapy to be withdrawn and facilitates improved care when therapy is required, with accompanying savings in costs and time. PMID- 2318374 TI - Measuring blood pressure in an inner city pharmacy: an attempt at coordination with general practice. AB - Free blood pressure checks, targeted at those aged 30 to 64 years, were offered for a six week period in a small inner city pharmacy. The pharmacist invited 120 clients to take part, of whom 70 (58%) accepted. Thirty of those having the check were interviewed. All had seen their general practitioner within the last five years, and half recalled having had a blood pressure check in the preceding 12 months. The 70 clients were given a copy of the result of the blood pressure check to return to their general practitioner. On checking the general practitioner record of 40 such patients, 25 (63%) had previous blood pressure recordings in the last five years. Only 10 (25%) contained the pharmacy reading, although the records of high readings were more likely to be present. The majority of the 14 general practitioners interviewed were unenthusiastic about the scheme. These results are not favourable to the idea of blood pressure screening by pharmacists, unless it is part of a major coordinated programme. PMID- 2318376 TI - Effect of a reading list on reading habits of general practitioners. PMID- 2318377 TI - Nutritional disorders associated with affluence in Bahrain. AB - In this paper the nutritional disorders associated with affluence in Bahrain are reviewed and analysed. Heart diseases, obesity, diabetes mellitus, cancer, and dental caries are becoming the main public health problems in the country. The major aetiological factors leading to such a situation are change in lifestyle, high per capita income, change in food consumption patterns, and ineffective preventive measures. Programmes to control the disease of affluence should be given a high priority in any health plan. Emphasis should be placed on initiating intervention nutrition programmes, training health staff and carrying out epidemiological studies. PMID- 2318378 TI - Sharing the pain--NIH institutes cope with lean times. PMID- 2318379 TI - Effect of buffer systems and pHi on the measurement of [Ca2+]i with fura 2. AB - The fluorescent probe, fura 2, is widely used to measure agonist-induced changes in intracellular calcium concentration ([Ca2+]i) in cultured cells. However, in many instances, the results obtained in the same cell type have differed from one study to the next. The possibility that such differences might be due to experimental conditions was examined by using fura 2 in four different cell types responding to appropriate agonists when the cells were incubated in either CO2/HCO3-- or HEPES-buffered media. Examined were: 1) the response of rat glomerular mesangial cells to arginine vasopressin, 2) the response of vascular smooth muscle cells to angiotensin II, 3) the response of adrenal glomerulosa cells to angiotensin II, and 4) the response of hypothalamic cells to insulin like growth factor-1. In each cell type there was a significant difference in the pattern of agonist-induced change in [Ca2+]i when HEPES vs. CO2/HCO3- was used as the buffer system: in HEPES buffer, agonist addition led to a transient rise in [Ca2+]i followed by a fall to a sustained plateau 27 to 34 nM higher than the original basal value, whereas in CO2/HCO3- buffer, agonist addition led to an identical transient increase in [Ca2+]i followed by a fall to a value within 10 nM or less of the preagonist level. The plateau value of [Ca2+]i in the different buffers was examined in relationship to known differences in intracellular pH (pHi). It was found that measurements of [Ca2+]i with fura 2 were influenced by shifts in pHi that occur when cells are incubated in either HEPES-buffered or CO2/HCO3- media of differing pHo values. However, at any given value of pHi, the apparent [Ca2+]i measured in cells incubated in HEPES-buffered media was slightly higher than in cells incubated in CO2/HCO3- buffered media. PMID- 2318381 TI - [25th forum on research in hepato-gastroenterology, 14th French-language seminar on hepatology and gastroenterology, 8th national continuing education seminar on hepato-gastroenterology. Paris, 24-28 March 1990. Abstracts]. PMID- 2318380 TI - Ex vivo lipopolysaccharide-induced interleukin-1 secretion from murine peritoneal macrophages inhibited by probucol, a hypocholesterolemic agent with antioxidant properties. AB - Probucol, 4,4'-(isopropylidenedithio)bis(2,6-di-tert-butyl-phenol), has been shown to inhibit atherogenesis in genetically hypercholesterolemic (Watanabe) rabbits. Since atherosclerotic lesions contain macrophages capable of screting interleukin 1 (IL 1) and other cytokines that could contribute to the pathogenesis of the disease, we have investigated whether probucol affects IL 1 secretion. Resident peritoneal macrophages from mice dosed with probucol secreted 40-80% less IL 1 than macrophages from control animals when stimulated in vitro with lipopolysaccharide (LPS). The inhibitory effect of probucol was observed when IL 1 was assayed by the standard bioassay, the thymocyte proliferation assay, or a competitive IL 1 receptor binding assay. Probucol treatment had no effect on LPS-induced membrane IL 1 expression; secretion of tumor necrosis factor (TNF); Con A-induced splenic interleukin 2 (IL 2) and interleukin 3 (IL 3) release; and prostaglandin- or zymosan-induced secretion of prostacyclin, leukotriene C4, acid phosphatase, or superoxide anion. In contrast to the effect of oral administration, direct addition of probucol to macrophage cultures did not inhibit IL 1 release. Probucol administration did, however, inhibit the fall in serum zinc level induced by intravenous injection of LPS in zymosan-primed mice but had no effect on the LPS-induced increase in serum triglyceride levels, which indirectly confirms that probucol administration inhibits IL 1 but not TNF secretion. Paw granuloma induced in mice by heat-killed mycobacteria was inhibited by oral administration of probucol, an effect that may be attributable to inhibition of IL 1 secretion. Probucol neither reduced zymosan-induced liver granulomata in mice nor inhibited adjuvant-induced arthritis in rats. We suggest that inhibition of IL 1 secretion from macrophages by probucol contributes to its therapeutic effects in atherosclerosis and may also result in beneficial activity in some chronic inflammatory diseases. PMID- 2318382 TI - Nontumorous attenuation differences on computed tomographic portography. AB - Nineteen patients with suspected hepatic neoplasms underwent dynamic computed tomography (CT) and computed tomographic porotography (CTP) in a preoperative setting. Nontumorous attenuation differences in the liver were observed in 8 patients (42%) with CTP and in 2 patients (10.5%) with dynamic CT (p less than 0.05). Although nontumorous attenuation differences are significantly more frequent with CTP than with dynamic CT, they are seldom a diagnostic problem because of their geographic pattern. PMID- 2318383 TI - Hepatic echinococcosis complicated with transphrenic migration and bronchial fistula: CT demonstration. AB - An unusual case of hepatic hydatidosis complicated by transphrenic migration of the hydatid cyst passing through the right hemidiaphragm, and penetrating the inferior pulmonary lobe causing a bronchial fistula, is presented. The computed tomographic (CT) study permitted the correct preoperative diagnosis. PMID- 2318384 TI - Percutaneous choledochoscopic choledocholithotomy in Caroli's disease. AB - Communicating cavernous ectasia of the intrahepatic bile ducts (Caroli's disease) is frequently accompanied by calculus formation. Percutaneous choledocholithotomy was successfully performed using a choledochoscope in a young adult with multiple calculi. To our knowledge this is the first reported case of choledocholithotomy using this technique in Caroli's disease. PMID- 2318385 TI - Tuberculous fistulas of the pharynx and esophagus. AB - Four patients with tuberculous fistulas communicating with the pharynx or the esophagus are reported. In 1 patient, there was strong evidence to suggest primary involvement of the esophageal mucosa. The other 3 cases were related to involvement of the pharynx or the esophagus from adjacent tuberculous process, as confirmed by histopathological proof. The patients had varying degrees of symptoms, which in two dramatically responded to antituberculous therapy; the third patient needed surgery for complete cure and the last patient was lost to follow-up. PMID- 2318386 TI - Radionuclide scintigraphy in tuberculous enteritis. AB - Scintigraphy with indium-111 labeled leucocytes and gallium-67 citrate was performed on 6 patients with proven tuberculous enteritis. The ability of both techniques to visualize areas of disease in this condition was demonstrated. When compared with endoscopy (either upper gastrointestinal endoscopy or colonoscopy), Ga-67 citrate had a sensitivity of 0.80 and a specificity of 1.00. The sensitivity and specificity of In-111 labeled leucocytes was 0.60 and 0.96, respectively. The superiority of Ga-67 over In-111 was statistically significant. Positive scintigrams were obtained despite prior treatment with antituberculous chemotherapy. PMID- 2318387 TI - Perforating duodenal diverticulitis. AB - Two cases of perforating duodenal diverticulitis are reported, one with enterolith formation, and the other with sonographic evidence of retroperitoneal emphysema. The possible complications of duodenal diverticula, as well as the difficulties encountered in preoperative diagnosis, are discussed. PMID- 2318388 TI - The value of double-contrast study of the small intestine in immunoproliferative small intestinal disease. AB - Radiological findings of 2 patients with immunoproliferative small intestinal disease were studied. One of the cases was associated with alpha-chain disease. Both patients complained of severe diarrhea, and diagnosis was made by endoscopic biopsy of the duodenum and jejunum. Double-contrast studies of the small intestine and hypotonic duodenographies in these patients revealed thickened folds and innumerable fine granular elevations without ulcerations or luminal narrowings. Double-contrast studies are one of the most important examinations in the diagnosis of this disorder. PMID- 2318390 TI - Digestive Disease Week and the 91st annual meeting of the American Gastroenterological Association. May 12-18, 1990, San Antonio, Texas. Program and abstracts. PMID- 2318389 TI - Rectal stenosis due to Veganine suppositories. AB - A new case of rectal stenosis due to the chronic use of suppositories of associated analgesic drugs is reported. Surgical treatment was conservative. This observation outlines the dramatic consequences of chronic self-treatment and the difficulties of ensuring long-term withdrawal. PMID- 2318391 TI - [Histologic studies of cartilaginous structures in the anterior region of the head of the sperm whale Physeter macrocephalus]. AB - Recently discovered cartilaginous structures in the forehead of the sperm whale (Behrmann and Klima 1985) were investigated histologically. The largest and most important of these structures is the nasal roof cartilage which can be derived from the tectum nasi, a part of the embryonic nasal capsule (Klima et al. 1986). In the investigated sperm whale fetuses, this structure consists of embryonic hyaline cartilage which is well suited for morphogenetic processes and fast growth. In the investigated adult sperm whale, the originally hyaline cartilage has been transformed into a special kind of elastic cartilage. The arrangement of cells, territories, and extracellular substance resembles hyaline cartilage. This component represents an adaptation to pressure load. The appearance and arrangement of elastic fibres resembles elastic cartilage. This component is an adaptation to distortion forces. Obviously, pressure and distortion are the strongest mechanical strains that the nasal roof cartilage is exposed. We see the function of this cartilage structure therein that, being a pressure-elastic skeletal support and following the left nasal meatus along its whole extension through the massive and soft forehead, it secures the only direct respiratory passage. Additionally, fibre bundles of transversely striated muscles are anchored in the perichondrium of the nasal roof cartilage. The function of this delicately interwoven muscle system is seen by us in the fine tuning of contraction and dilatation of the respiratory passage. Moreover, a possible function as a sound conducting cartilaginous structure serving the echolocation system is considered (c.f. Pilleri et al. 1983). PMID- 2318392 TI - Fine structure of the boundary tissue of the seminiferous tubuli of the vampire bat (Desmodus rotundus, G.; Microchiroptera). AB - Structurally the boundary tissue of the vampire bat seminiferous tubuli showed 2 to 5 layers of connective tissue in which elongated contractile cells and lamellar and/or fibrillar collagen were noticed. This boundary tissue forms the seminiferous tubular lamina propria. Its structure was more complex around the seminiferous tubuli near the Capsula testicularis than between the adjacent and contiguous tubuli into the testicular lobuli. The whole ultrastructural organization of the seminiferous lamina propria was described here. PMID- 2318393 TI - Fine structure of the ductuli efferentes of the hamster (Mesocricetus auratus). AB - Structurally the ductuli efferentes of the hamster showed 2 distinct segments, a testicular and an epididymal. Both of these segments were lined by a pseudostratified epithelium, which showed basically non-ciliated and ciliated cells. In the testicular segment a 3rd type of oval dark cells was observed. The ultrastructural characteristics of these cells were presented and discussed in this report. PMID- 2318394 TI - Morphological aspects of the esophagus and stomach of a freshwater iliophagous fish under scanning electron microscopy. AB - The esophagus and the stomach of the teleost fishes are sometimes non differentiable during macroscopic analysis. The scanning electron microscope allowed to characterize those 2 organs in Prochilodus scrofa, also revealing the presence of a short transition segment. The characteristics of the mucosal and surface cells relief were also studied. PMID- 2318395 TI - [Causes of variations in the pathway of the basilar and vertebral arteries]. AB - Artery loops at the root exit zones of cerebral nerves are regarded as causes of certain diseases, e.g. trigeminal neuralgia or hemifacial spasm. The factors, which may cause such loops and displacements of arteries, however, are still not known sufficiently. In order to find out more about such causes, 60 corpses were examined. We recorded the variations in the positions of vertebral and basilar arteries and correlated them with the respective age at the time of death. We found that those showing atypical artery positions and loops were generally of older age. We further examined possible influences of blood flow factors on variations of artery positions. Our sample indicated such influence of flow factors on displacements of basilar artery, but they seemed to be of lesser importance than the effect of ageing. PMID- 2318396 TI - [12th meeting of the Anatomists of the Alpine Countries. Innsbruck, Austria, 4-6 May 1989. Abstracts]. PMID- 2318397 TI - [Kinematics and dynamics of the temporomandibular joint and of the movements of the mandible]. AB - In order to analyze the complicated movements of the mandible as the open-closing movement and the protrusio are, it is useful to evaluate the basic kinematic principles and reduce them to simple technical constructions. Both the open closing movement and the protrusio could be reduced to 4-bar links, which were used to simulate the movements with help of a computer. Besides, the polodes and the curves of points in the muscular attachments could be constructed. The 2 entirely different 4-bar links have 3 things in common: The resting system - cranium, the moving system - mandibula, and 1 of the 2 arms connecting these 2 systems - the ligamentum laterale. As this ligament is taut during movements it can be considered a "guiding ligament" representing 1 of the 3 determining components of the mandibular movements. The other of the 2 arms has no anatomical equivalent; this arm, however, is "replaced" by the 2 other determining components of the mandibular movements: the joint and the muscles. The curves, which the Caput mandibulae describes, are practically identical for the open closing movement and the protrusio despite of the different 4-bar links and these curves exactly correspond to the Discus articularis, taut by the upper part of the M. pterygoideus lateralis. The muscles do not only just move the mandibula, but they are also the component, which can choose between the different mandibular movements. By means of the curves, which points in the muscular attachments describe, the function of the masticatory muscles could be analyzed exactly. PMID- 2318399 TI - Direct branch of external carotid: a masseteric artery. AB - An additional branch of the right external carotid in the form of an unusual direct artery to m. masseter is described. It arose as a terminal branch along with the maxillary and superficial temporal arteries, ran in the substance of the parotid gland to supply the muscle on its lateral aspect. The pertinent anatomical literature is reviewed. PMID- 2318398 TI - [The morphology of the esophageal mucosa of the rat: a scanning electron microscopic study]. AB - The morphology of the oesophageal mucosa of adult male and female albino rats (Rattus norvegicus) is studied by means of scanning electron microscopy of several levels. A precise surface analysis of the upper, middle, and lower portion of the esophagus is done and the results are compared with each other. PMID- 2318400 TI - [Histochemical studies of the kidney of white rats after experimental external application of sulfur mustard gas]. AB - After the experimental application of sulphur mustard contained in Psoriazin produced by Medexport, the kidney of white rats is examined by means of histologic and histochemical methods. It was noted that the prolonged application of Psoriazin caused changes in the convoluted tubules. PMID- 2318401 TI - Histological alterations by a diet containing seeds of Garcinia kola: effect on liver, kidney, and intestine in the rat. AB - Histological examination of liver, kidney, and duodenum of rats fed a diet containing 10% (w/w) dry powdered seeds of Garcinia kola for 6 weeks revealed cellular changes that were not observed in pair-fed control animals. The main cellular changes observed in the rats fed on Garcinia kola diet included vacuolation of duodenal villous epithelial cells, numerous intracytoplasmic vacuoles in hepatocytes, and mild hydropic degeneration in cells of the renal proximal tubular epithelium. These changes are probably due to the flavonoids contained in G. kola seeds. PMID- 2318402 TI - [Diagnosis of prospective malignancy of cervix dysplasia using DNA cytometry]. AB - 134 borderline lesions of the cervix uteri (CIN I/II) were investigated by using the newly developed diagnostic method DNA-image cytometry (MIAMED-DNA, Wild Leitz, Wetzlar). The demonstration of aneuploid cells served as a marker for prospective malignancy. 18 out of 35 cases, which proved to be CIN III in the follow-up, had a malignant DNA diagnosis. The sensitivity of the diagnostic DNA cytometry for prospective malignancy was therefore 51.4%. All 43 cases with a negative DNA diagnosis proved to be negative in the follow-up, so that the specificity of DNA cytometry was 100%. Suspicious DNA diagnosis in 26% of the cases proved to be CIN III in the follow-up. DNA cytometry seems to be a reliable method to predict the biological behaviour of borderline lesions of the cervix uteri in everyday practice. PMID- 2318403 TI - [Is consecutive curettage of the corpus uteri indicated in every conization case?]. AB - Endometrial curettage at the time of conisation is often performed as a routine procedure, even when indication for this treatment is rather unclear. 593 conisations including curettages were performed at the I. Department of Obstetrics and Gynaecology, of the University of Vienna and were evaluated retrospectively. Only 3 patients with a mild endometrial hyperplasia were found. Therefore, in our opinion, there is no indication for a curettage at the time of conisation, if a woman is under the age of 35 years and if there is no other specific indication for sampling the endometrium, based on high risk factors, physical examination, history or abnormal glandular cells found on cervical cytology. Such management would result in reducing the costs and the risk of infection in intrauterine operations. PMID- 2318405 TI - [The effect of intrauterine growth retardation and gestational age on status praesens of the newborn infant]. AB - We investigated on the basis of 14,498 singleton births between the completed 24th and 42nd week of pregnancy, the dependence of the Apgar index after one minute and of the actual pH in the umbilical artery on two clinical variables 1. the duration of gestation and 2. the degree of intrauterine growth retardation. To determine the latter, each of the 14498 infant weights was transformed arithmetically to a percentile, i.e. a figure between 0 and 100. It was shown that the duration of pregnancy has a significant effect on increasing foetal acidity, which is greater (nonlinear correlation), the more immature the baby is. The influence of intrauterine growth retardation is slight but demonstrable in mature neonates and with adequate clinical management. In premature infants, especially in very small premature babies, intrauterine growth retardation becomes a major risk factor: increasing hypotrophy leads to a probably exponential rise of the acidity figures as well as to an increase in the percentage of low and very low Apgar scores. Hypertrophic premature babies and hypertrophic mature neonates are also subject to an increased risk. The effects mentioned above, of clinical maturity and intrauterine nutrient and oxygen supply on the unborn baby, result in a numerical continuity in the behaviour of the parameters: there are no abrupt alterations. This suggests, that the conventional definitions of hypotrophy or hypertrophy should be reconsidered. Furthermore, the data allow the conclusion, that prematurity and dysmaturity are two important variables thus suggesting an individual (i.e. non-schematic) obstetric procedure in premature deliveries. PMID- 2318404 TI - [Modulation of hCG synthesis by alpha tumor necrosis factor in JAR choriocarcinoma cells]. AB - The tumour necrosis factor (TNF) stimulates in cultured JAR choriocarcinoma cells the biosynthesis of hCG, including the free alpha and beta chain and the holo hCG. Although elevated serum TNF levels have been shown by Balkwill et al. (1987) in about 50% of tumour patients, we were unable to confirm these data in the 10 examined patients, who had a choriocarcinoma. Despite its excellent in-vitro action, INF could not be confirmed to exercise an influence on the regulation of hCG in choriocarcinoma patients. PMID- 2318406 TI - [Pregnancy and labor in idiopathic thrombocytopenic purpura (Werlhof disease)]. AB - The managing of the pregnant patient with immune thrombocytopenic purpura (ITP) is complicated by the unavailability of the foetal platelet count and the risk of bleeding. We report on our experiences of 17 pregnancies in 15 patients, who delivered in the Department of Gynaecology of Freiburg University from 1969 to 1989 (frequency: 0.5 per 1,000). ITP was established prior to pregnancy in 9 of 15 patients, and developed in 6 cases during pregnancy. The a patients received steroid therapy ante partum. However, maternal platelet count did not relate to infant platelet count. Eleven infants were born vaginally, six by caesarean section. One of the 17 live births died immediately post partum at the 28th week of gestation. Six infants were temporarily thrombocytopenic at delivery without further morbidity. Based on our experience and the literature, an individual management of delivery for parturient patients with ITP is recommended. PMID- 2318407 TI - [Urodynamics and the lateral cystogram: value for incontinence diagnosis]. AB - We compared urodynamic findings and results of lateral cystourethrography in 82 patients with incontinence. The aim of the study was to establish a possible correlation between anatomic findings and functional results. Clinically, a significantly higher increase of the posterior urethrovesicular angle was noted in patients with a urodynamic stress incontinence than in patients with urge incontinence or those with normal urodynamic findings. Lateral cystourethrography as compared to urodynamic assessment, proved to be a method with high sensitivity (91%) but little specificity. These two methods supply different but complementary data. Together with history, assessment of patients' complaints, clinical vaginal examination, and clinical stress test they offer valuable information for an efficient therapeutic concept. PMID- 2318408 TI - [Clinical experiences with magnetic urethral closure]. AB - The new magnetic closure device consists of a retropubically implanted magnet. Another removable magnet is situated in the vagina, when the patient is physically active and when continence is desired. The system has been used in 11 patients with up to 5 years follow-up observation. PMID- 2318409 TI - [Multifocal carcinoma of the upper female genital tract: diffuse Mullerian neoplasia]. AB - The simultaneous occurrence of moderately differentiated mesonephroid adenocarcinomas of the endocervix and the ovary and a well differentiated adenocarcinoma of the endometrium in a 46-year-old woman are reported. The problems of classification as multiple primary neoplasma or as metastatic spread are discussed. Histogenesis of multiple primary epithelial malignancies of the female genital tract is explained by the theory of area response of embryologically related organs to an unknown carcinogenic stimulus. PMID- 2318410 TI - [Fetal emergency--compromise of parental guardianship already in unborn children?]. PMID- 2318411 TI - Search for differences among t haplotypes in distorter and responder genes. AB - Transmission ratio distortion due to the mouse t complex is though to be due to harmful effects of trans-acting distorter genes acting on a responder, with the t complex form of the responder being relatively resistant to this harmful action of the distorters. Previous work had indicated that naturally occurring t haplotypes differed in their responders or in distorters lying near the responder, with the result that animals doubly heterozygous for two responder carrying haplotypes transmitted these haplotypes unequally. In the present work t haplotypes could be divided into three types on the basis of their transmission when doubly heterozygous with the responder-carrying partial haplotype tlowH. The majority, t0, t6, tw1, tw2 and tw73, were transmitted equally with tlowH, a second group, including tw5 and two haplotypes derived from it, were transmitted less frequently than tlowH, and the single member of a third group, tw32, was transmitted in excess of tlowH. This last result suggests that the underlying differences are in the responder itself, rather than in the distorters. Search for differences among t haplotypes in distorters produced some equivocal results possibly resulting from effects of genetic background. In particular, results of others suggesting presence of a fourth distorter, Tcd-4, were not confirmed. PMID- 2318412 TI - The extended survival of tw5/tw5 mouse embryo cells in vitro. AB - The tw5 haplotype is a recessive mutation which is lethal when homozygous in mouse embryos following implantation. This series of studies was undertaken to determine the effect of the tw5/tw5 genotype on embryos developing in vitro. Blastocyst embryos from +/tw5 inter se matings were compared with control blastocysts obtained from matings between T/+ and +/+ females and +/tw5 males for their abilities to continue development in vitro in two culture media. The data show that there are no significant differences between the percentages of experimental and control blastocyst embryos which attach and outgrow or which contain inner cell masses on any day of culture up to equivalent gestation day 21 in either media. These findings show that the life span of cells from tw5/tw5 embryos can be extended significantly by in vitro culture. PMID- 2318413 TI - The induction of tail malformations in trisomy 16 mouse fetuses heterozygous for the curly tail recessive gene. AB - The mouse mutant curly tail is thought to be inherited as an autosomal recessive (ct/ct) with incomplete penetrance so that approximately 60% of ct/ct individuals exhibit the curly tail (CT) phenotype. By outcrossing ct/ct with mouse stock carrying specific heterozygous combinations of Robertsonian (Rb) chromosomes, trisomy 16 (Ts16) and Ts19 mouse fetuses (and their chromosomally balanced littermates) were derived which were heterozygous for the ct gene. All of the Ts16 (ct/Rb;Rb) fetuses, studied between days 14-19 gestation had tail malformations, 86% of which were tail flexion defects (TFD) apparently very similar to the curly tail phenotype. Neither Ts19 nor any of the chromosomally balanced (ct/Rb) littermates from both experimental crosses showed any type of tail or other spinal malformation. At the 27-29 somite stage of development, Ts16 (ct/Rb;Rb) fetuses did not show any significant delay in the closure of the posterior neuropore (PNP) compared with their littermate controls, suggesting that the tail malformation observed in Ts16 (ct/Rb;Rb) occur as a result of mechanisms which differ significantly from those thought to be responsible to causing the curly tail malformation. PMID- 2318414 TI - Evidence for a new major gene influencing meat quality in pigs. AB - The present investigation primarily deals with the inheritance of a pigmeat quality trait, the Napole technological yield (RTN), a measure of cooked weight to fresh weight. This trait as well as lean percentage at 100 kg liveweight and fattening length from 20 to 100 kg liveweight were recorded on 3459 offspring from 67 sires and 433 dams, and 3052 offspring from 64 sires and 405 dams in Penshire (P66) and Pen Ar Lan (P77) composite lines respectively. The hypothesis of a major 2-allele locus contributing to RTN was tested by use of a segregation analysis method. Highly significant likelihood ratios (mixed vs. polygenic transmission models) lead us to conclude that a major gene RN- exerting an unfavourable effect on RTN is segregating in both lines. Maximum likelihood estimates of the parameters under the hypothesis of mixed (monogenic + polygenic) inheritance show that the difference between the means of the 2 homozygotes amounts to about 3 phenotypic standard deviations of the trait, whereas the complete dominance of RN- cannot be rejected. The frequency of RN- is about 0.6 in both lines. These results are discussed in connection with the previously reported 'Hampshire effect' on pigmeat quality, as the Hampshire breed is a common component of the foundation stock of the 2 composite lines under study. PMID- 2318415 TI - Prediction of rates of inbreeding in selected populations. AB - A method is presented for the prediction of rate of inbreeding for populations with discrete generations. The matrix of Wright's numerator relationships is partitioned into 'contribution' matrices which describe the contribution of the Mendelian sampling of genes of ancestors in a given generation to the relationship between individuals in later generations. These contributions stabilize with time and the value to which they stabilize is shown to be related to the asymptotic rate of inbreeding and therefore also the effective population size, Ne approximately 2N/(mu 2r + sigma 2r), where N is the number of individuals per generation and mu r and sigma 2r are the mean and variance of long-term relationships or long-term contributions. These stabilized values are then predicted using a recursive equation via the concept of selective advantage for populations with hierarchical mating structures undergoing mass selection. Account is taken of the change in genetic parameters as a consequence of selection and also the increasing 'competitiveness' of contemporaries as selection proceeds. Examples are given and predicted rates of inbreeding are compared to those calculated in simulations. For populations of 20 males and 20, 40, 100 or 200 females the rate of inbreeding was found to increase by as much as 75% over the rate of inbreeding in an unselected population depending on mating ratio, selection intensity and heritability of the selected trait. The prediction presented here estimated the rate of inbreeding usually within 5% of that calculated from simulation. PMID- 2318416 TI - Photoaging and the skin: differentiation and clinical response. AB - Extrinsic aging changes caused by habitual exposure to ultraviolet light are often erroneously confused with intrinsic aging alterations due to chronologic aging. We compare the clinical, histologic, and biochemical changes related to chronic sun exposure--photoaging--with normal skin changes related to aging. PMID- 2318417 TI - Current management modalities for prostate cancer. AB - Prostate cancer remains one of the leading causes of morbidity and mortality in elderly men. It is the second most common form of malignancy and the third leading cause of cancer deaths. The cause remains unknown, and only with early detection can this illness be cured. Unfortunately, early warning signs are rare, but any change in urinary pattern should be considered due to prostate cancer until proven otherwise. This discussion will focus on pathophysiology, diagnosis, early detection, evaluation, staging, and treatment modalities for prostate cancer. PMID- 2318418 TI - The case for dietary management of the older hypertensive. AB - If the expense or side effects of antihypertensive drug therapy become a serious problem, dietary therapy can be a worthwhile option. The dietary prescription for treatment of hypertension usually involves modifications in energy, fat, and minerals. Weight, blood cholesterol, and triglycerides should be controlled through dietary management. Sodium's effect on blood pressure is controversial and not clearly defined; however, sodium restriction is usually prescribed for hypertensive patients because of potential benefits. Other minerals that may affect blood pressure include potassium and calcium. Good dietary intake of both minerals has been associated with lowered blood pressure. An accompanying scenario illustrates the effectiveness of dietary management. PMID- 2318419 TI - Major thiobarbituric acid-reactive substances of liver homogenate are alkadienals. AB - Thiobarbituric acid (TBA) assay of rat liver homogenate was performed by four general variations with 0.01% butylated hydroxytoluene. Development of red pigment was greatly dependent on the methods. The pigment formation by each method was dramatically increased by introduction of 2 mM t-butyl hydroperoxide (t-BuOOH). The pH values of the reaction mixtures greatly affected the pigment yield both in the absence and presence of t-BuOOH, and the maximal pigment yield was obtained at pH 3-4. These characteristic profiles of the pigment formation were similar to those from alkadienals and essentially different from those from malonaldehyde. Alkadienals were likely candidates for the TBA-reactive substances in the homogenate. PMID- 2318420 TI - Diazoluminomelanin: a synthetic luminescent biopolymer. AB - The purpose of this work was to synthesize a water-soluble derivative of 5-amino 2, 3-dihydro-1, 4-phthalazinedione (luminol) that generated sustained high level luminescence under physiologic conditions without the necessity of a catalyst. The derivative was made by a diazotization reaction with luminol and 3-amino-L tyrosine. The resulting orange-brown anionic polymer has been given the trivial name of diazoluminomelanin (DALM). It was water soluble above and insoluble at or below pH 5.0. DALM luminesced when treated with hydrogen peroxide without the presence of a catalyst at pHs ranging from 6.5 to 12.0. Microgram quantities produced high levels of chemiluminescence for longer than 52 hr. Dried polymer generated a long-term stable electron spin resonance spectrum. The long-term chemiluminescence of DALM at pH 6.8-7.4 makes it a potentially useful reagent for detecting free radicals and peroxides in cellular and biochemical preparations. PMID- 2318421 TI - Excretion of hydrogen peroxide in human urine. AB - The excretion of hydrogen peroxide in human urine has been demonstrated for the first time. This was accomplished by a new radioactive method developed on the basis of decarboxylation of alpha-ketoglutaric acid by H2O2. Urine samples were incubated with alpha ketoglutarate pulsed with iwts 1-14C-analogue, and CO2 formed by decarboxylation was determined by radioactivity measurements. Blanks were prepared by pre-incubation of the samples with catalase. Both male and female subjects were studied. On an average the concentration of H2O2 in urine was approximately 100 +/- 60 microM (10(-4) M). Peroxide excretion was found to be unexpectedly high and might thus be useful for clinical diagnosis and therapy in diseases purported to be related to oxidative stress. PMID- 2318422 TI - Effect of ischaemia-reperfusion on glutathione peroxidase, glutathione reductase and glutathione transferase activities in human heart protected by hypothermic cardioplegia. AB - The activities of glutathione peroxidase (GSH-px), glutathione reductase (GSSG rx) and glutathione transferase (GST) were measured in myocardial specimens obtained from right atria of patients subjected to different period of ischaemic arrest (aortic clamping ranging from 10 min to 90 min) followed by 60 min. of reperfusion, during open heart surgery 41-90 min. period of aortic clamping induced a significant increase of GSH-px activity with both H2O2 (p less than 0.05) and cumene hydroperoxide (p less than 0.025) as substrates when compared with baseline levels. Aortic clamping and reperfusion, however did not significantly change the myocardial activities of glutathione transferase and glutathione reductase. It is suggested that the increase of GSH-px in ischaemic reperfused human hearts may render the myocardium less susceptible to oxidative attack particularly during the reoxygenation period when the level of active oxygen species is greatly elevated. PMID- 2318424 TI - Non-invasive method for delivery of tracer substances or small quantities of other materials to the colon. AB - A miniature osmotic pump has been developed (Osmet) with ALZA, Palo Alto, USA, which can be swallowed, will pass through the stomach and small intestine and then deliver its contents (240 microliters) over eight hours in the large bowel. In vitro studies showed the pumps started to discharge after four to five hours and emptied at a reasonably constant rate of 20.4 microliters/h from 9-16 h (9.6%/h). In vivo studies using gamma-scintigraphy in seven healthy subjects show that the pumps left the fasting stomach at 1.2 h (range 0-3) and arrived in the caecum by 6.4 h (range 5-9). Mean start-up time was 5.3 (0.2) h and the rate of discharge was 15.9 microliters/h for pumps studied from 6-12 h and 17.2 microliters/h for those studied from 10-20 h. This device is simple, safe and effective for the delivery of tracer substances to the caecum and colon without interfering with patients' normal lifestyle. PMID- 2318423 TI - Quantitative ultrastructural studies of gall bladder epithelium in gall stone free subjects and patients with gall stones. AB - The present study aimed at a further evaluation of the role of glycoproteins in the formation of cholesterol gall stones in man. An electron microscopic morphometric study of the gall bladder epithelium was performed in six gall stone free subjects and 12 gall stone patients. Six of the gall stone patients were treated with ursodeoxycholic acid three weeks before cholecystectomy. The number and the volume density of the mucin containing secretory granules, were not significantly increased in gall stone patients compared with gall stone free subjects. Treatment with ursodeoxycholic acid did not affect the number or volume density of the secretory granules. Thus, these results do not give evidence for that the degree of cholesterol saturation influences mucin content in the gall bladder wall of man. A major new finding was that gall stone patients had a markedly reduced total lysosome area and volume density of lysosomes compared with gall stone free subjects, a finding which may be related to a decreased intracellular degradation of protein and/or mucin. PMID- 2318425 TI - Peptic ulcer in India. PMID- 2318426 TI - Short bowel syndrome and somatostatin 201-995. PMID- 2318427 TI - Effects of postganglionic nerve stimulation in oesophageal achalasia: an in vitro study. AB - The functional postganglionic innervation of isolated smooth muscle strips from the oesophagogastric junction was examined in specimens taken from six achalasia patients and seven controls. Muscle strips representing either the longitudinal or the circular layer were prepared and mounted in organ baths and isometric tension was recorded. Electrical field stimulation, selectively exciting nerves, was applied. Strips from the circular layer from controls relaxed during field stimulation, an effect that was the result of stimulation of noncholinergic, non adrenergic, inhibitory nerves. Circular muscle strips from achalasia patients contracted during field stimulation, an effect that was caused by muscarinic receptor activation. In one patient, atropine reversed the contraction to a relaxation. Longitudinal muscle strips contracted in response to stimulation in both controls and achalasia patients. This response was abolished by atropine. In conclusion the function of postganglionic inhibitory nerve fibres to the circular layer of the oesophagogastric junction is severely impaired in achalasia, while there is a conspicuous, functional cholinergic innervation. PMID- 2318428 TI - Effect of bismuth subcitrate and sucralfate on rat duodenal and human gastric bicarbonate secretion in vivo. AB - Acid and alkali secretion have been examined together with prostaglandin E2 production in response to two mucosal protective drugs, colloidal bismuth subcitrate and sucralfate. Doses of colloidal bismuth subcitrate in the therapeutic range (120 and 1200 mg) had no effect on alkali secretion or luminal PGE2 output when perfused into the stomach of human volunteers. Similarly, in the anaesthetised rat, neither gastric acid nor duodenal alkali secretions were influenced by iv (12 mg/kg) or topical (120 mg/ml) administration of colloidal bismuth subcitrate. In contrast, perfusion of the human stomach with 1 g sucralfate stimulated bicarbonate output by 50%, a response which was unaffected by indomethacin (25 mg/h). A rise of 64% in gastric PGE2 output after sucralfate was, however, prevented by indomethacin pretreatment. Alkali secretion by rat duodenum was also increased by sucralfate but the response depended on the basal secretory rate. Low basal secretors (less than 3 mumol) showed a 75% stimulation whereas rats with high basal secretory rates (greater than 3 mumol) showed no significant response. All duodenal preparations regardless of basal secretory rate showed a stimulation of bicarbonate output with topical PGE2. The results suggest that enhancement of gastroduodenal bicarbonate secretion may play a role in the protective action of sucralfate but is unlikely to explain mucosal protection by colloidal bismuth subcitrate. PMID- 2318429 TI - Studies of intestinal lymphoid tissue. XIV--HLA status, mucosal morphology, permeability and epithelial lymphocyte populations in first degree relatives of patients with coeliac disease. AB - Fifty two first degree relatives of patients with coeliac disease were investigated for HLA status, small intestinal permeability, and mucosal morphology together with the size of the intraepithelial lymphocyte pool and indices of lymphocyte activation, in an attempt to identify genetically determined markers of the disease. Thirty eight per cent of these subjects had increased intraepithelial lymphocyte populations and a highly significant association with HLA-DR3 compared with controls. Their intestinal permeability to 51chromium-labelled ethylenediamine tetraacetate was invariably normal and there was no evidence of abnormal mucosal architecture, increased crypt cell mitotic activity or lymphocyte 'activation'. Although increased intraepithelial lymphocyte counts clearly do not cause alterations in intestinal structure or function, it is likely that this parameter together with the HLA-DR3 status identifies a genetically determined predisposition to the disease which may only become clinically evident with larger doses of ingested gluten. PMID- 2318430 TI - Interval sampling of end-expiratory hydrogen (H2) concentrations to quantify carbohydrate malabsorption by means of lactulose standards. AB - Lactulose H2 breath tests are widely used for quantifying carbohydrate malabsorption, but the validity of the commonly used technique (interval sampling of H2 concentrations) has not been systematically investigated. In eight healthy adults we studied the reproducibility of the technique and the accuracy with which 5 g and 20 g doses of lactulose could be calculated from the H2 excretion after their ingestion by means of a 10 g lactulose standard. The influence of different lengths of the test period, different definitions of the baseline and the significance of standard meals and peak H2 concentrations was also studied. Regardless of baseline definition, estimates of malabsorption were most precise, if areas under the H2 concentration v time curves for four hours or more from the start of the excess H2 excretion were used. The median deviations from the expected values were 20-30% (5-60%, interquartile range). This corresponded to the deviation in reproducibility of the standard dose. We suggest that individual estimates of carbohydrate malabsorption by means of H2 breath tests should be interpreted with caution if tests of reproducibility are not incorporated. Both areas under curves and peak H2 concentrations seem valid for comparison of groups. PMID- 2318431 TI - Mechanisms of acid reflux associated with cigarette smoking. AB - Studies were done to evaluate the lower oesophageal sphincter function of chronic smokers compared with non-smokers and to ascertain the acute effects of smoking on the sphincter and the occurrence of acid reflux. All subjects (non-smokers, asymptomatic cigarette smokers, and smokers with oesophagitis) were studied postprandially with a lower oesophageal sphincter sleeve assembly, distal oesophageal pH electrode, and submental electromyographic electrodes. The two groups of cigarette smokers then smoked three cigarettes in succession before being recorded for an additional hour. As a group, the cigarette smokers had significantly lower lower oesophageal sphincter pressure compared with non smokers but the sphincter was not further compromised by acutely smoking cigarettes. Cigarette smoking did, however, acutely increase the rate at which acid reflux events occurred. The mechanisms of acid reflux during cigarette smoking were mainly dependent upon the coexistence of diminished lower oesophageal sphincter pressure. Fewer than half of reflux events occurred by transient lower oesophageal sphincter relaxations. The majority of acid reflux occurred with coughing or deep inspiration during which abrupt increases in intra abdominal pressure overpowered a feeble sphincter. We conclude that cigarette smoking probably exacerbates reflux disease by directly provoking acid reflux and perhaps by a long lasting reduction of lower oesophageal sphincter pressure. PMID- 2318432 TI - Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. AB - The aim of this study was to evaluate the clinicopathological spectrum of eosinophilic gastroenteritis and identify possible difficulties in establishing the diagnosis. All patients with a diagnosis of eosinophilic gastroenteritis, defined by the presence of gastrointestinal symptoms and eosinophilic infiltration of the gut (38), or a radiological diagnosis with peripheral eosinophilia (two), were identified from the Mayo Clinic records; in none was there evidence of extraintestinal disease. Patients were divided into three groups according to the Klein classification: predominant mucosal (23), muscular (12), or subserosal disease (five). A fourth group of patients (10) for comparison had abdominal symptoms and unexplained peripheral eosinophilia but no proven eosinophilic infiltration of the gut. It was found that a history of allergy was reported by 20 of 40 patients with eosinophilic gastroenteritis. Peripheral eosinophilia was absent in nine of 40. The patients with subserosal disease were distinct from the other groups in presentation (abdominal bloating, ascites), higher eosinophil counts and in their dramatic responses to steroid therapy. Otherwise the patients were similar regarding demographic factors, presenting symptoms (abdominal pain, nausea, weight loss, diarrhoea), and laboratory parameters. The ESR was moderately raised in 10 of 40 patients. The disease may affect any area of the gastrointestinal tract; eosinophilic infiltration was documented in the oesophagus in one patient and in the colon in two cases. Endoscopic biopsies missed the diagnosis in five of 40 presumably because of patchy disease. Eosinophilic gastroenteritis should be considered in the differential diagnosis of unexplained gastrointestinal symptoms even in the absence of peripheral eosinophilia. PMID- 2318433 TI - Diagnostic value of the Manning criteria in irritable bowel syndrome. AB - Because unexplained 'functional symptoms' are a major cause of referral to gastroenterologists, the efficiency of the medical history to lead to a positive diagnosis of irritable bowel syndrome, without resorting to the use of expensive tests, remains a key question. Whilst the six criteria of Manning et al are widely used, data on their validity in discriminating irritable bowel syndrome from healthy controls, irritable bowel syndrome from non-ulcer dyspepsia and especially among irritable bowel syndrome subgroups, are not available. To evaluate this, we studied 361 outpatients who completed a bowel disease questionnaire, which objectively measured Manning's (and other) criteria. The group included 82 patients with irritable bowel syndrome, 33 with non-ulcer dyspepsia, 101 with organic gastrointestinal disease, and 145 healthy controls. Diagnoses were based on a full and independent clinical evaluation, not on responses to the bowel disease questionnaire. Reliability was assessed by a test retest procedure. All six of the individual Manning criteria were found to be reliable (median kappa = 0.79). Based on a logistic regression analysis of the discriminatory value of Manning's criteria, as the number of positive criteria increased, so did the predicted probability of irritable bowel syndrome. This predictive value was highest in younger patients and in females. The Manning criteria discriminated irritable bowel syndrome from organic gastrointestinal disease and from all non-irritable bowel syndrome gastrointestinal disease with a sensitivity of 58% and 42%, and a specificity of 74% and 85%, respectively. Stools that were often loose and watery provided an additional independent criterion for distinguishing irritable bowel syndrome from non-irritable bowel syndrome. Thus, symptoms can be used to diagnose irritable bowel syndrome positively, but Manning's criteria are not highly sensitive. PMID- 2318434 TI - Osteoporosis and skeletal fractures in chronic liver disease. AB - In order to determine the prevalence and severity of hepatic osteodystrophy by non-invasive means we compared 115 consecutive ambulant patients with histologically proven chronic liver disease to 113 age and sex matched control subjects. Methods used included the assessment of fracture prevalence rates, spinal radiography, and measurements of bone mineral density in the spine and the forearm. Spinal and peripheral fractures were more prevalent in the patients than in the control subjects (p less than 0.03 and p less than 0.01 respectively). The type of the underlying liver disease did not significantly affect the fracture prevalence rates, but alcoholic patients sustained more peripheral fractures than patients with other hepatic disorders (p less than 0.05). The bone mineral densities of the spines and the forearms were significantly reduced in male patients of all age groups and in female patients aged 60 years or more (p less than 0.001 for men and p less than 0.01 for women for both measurements). The prevalence rates of spinal and forearm osteoporosis were twice as high among patients with liver disease than in control subjects regardless of the definitions used. The presence of cirrhosis and hypogonadism were major risk factors for development of both spinal (Beta coef = 0.190 and 0.176; SE = 0.079 and 0.086 respectively) and forearm osteoporosis (Beta coef = 0.20 and 0.29; SE = 0.073 and 0.80 respectively). Spinal bone density was the predominant determinant of spinal fractures (Beta coef = -0.007; SE = 0.001), while hypogonadism (Beta coef = 0.363; SE = 0.075) and cirrhosis (Beta coef = 0.185; SE = 0.068) were the major predictors of peripheral fractures. The concentrations of serum calcium and serum vitamin D metabolites and the use of corticosteroids were apparently without effect on the prevalence of skeletal fractures or bone density. PMID- 2318435 TI - Low molecular weight IgM in primary biliary cirrhosis. AB - Low molecular weight IgM is the monomeric subunit of pentameric IgM and is not generally found in the blood of healthy individuals. Using a sensitive immunoblotting technique, low molecular weight IgM was detected in all 17 patients with primary biliary cirrhosis and constituted up to 5% of the total circulating IgM. This low molecular weight IgM moiety correlated significantly with total IgM (p less than 0.01) but not with the specific biliary cirrhosis mitochondrial autoantibody anti-M2. Furthermore it was not possible to show that a partially purified sample of low molecular weight IgM contained M2 binding activity. Mitogen stimulated peripheral blood mononuclear cells from two of four patients were observed to secrete low molecular weight IgM in vitro, a finding seen in only one of six healthy subjects. Immunoblot analysis of patients sera revealed the presence of other oligomers of IgM in addition to low molecular weight IgM. In conclusion this study suggests that during the enhanced IgM synthesis observed in primary biliary cirrhosis a defect occurs in the assembly of the IgM pentamer with release of monomeric and oligomeric IgM into the circulation. The pathogenic significance of these circulating low molecular weight IgM species is unknown. PMID- 2318436 TI - Effect of gastrin on liver regeneration after partial hepatectomy in rats. AB - Gastrin has been shown to be an important trophic hormone for the mucosa of the stomach and the proximal intestine. In the present study the effect of gastrin on liver regeneration after partial hepatectomy in rats was investigated. After partial hepatectomy a significant rise in the concentration of gastrin in portal venous blood was found six, 12, and 18 hours after 70% hepatectomy. The effect of changes in the endogenous gastrin concentration on the liver regeneration was investigated in rats subjected to antrectomy or to fundectomy. Partial hepatectomy was done three weeks after the primary surgery. We found antrectomy to decrease liver regeneration, whereas fundectomy had no effect. Administration of pentagastrin 300 micrograms/kg sc three times daily for two and four days after partial hepatectomy significantly increased the rate of liver regeneration compared with controls. This study suggests that gastrin has a hepatotrophic effect. Whether this effect is caused by a direct action of gastrin on the hepatocytes or it is an indirect effect mediated by for instance insulin, glucagon or epidermal growth factor has to be further investigated. PMID- 2318437 TI - Treating UTIs. PMID- 2318438 TI - Prospective evaluation of serum CA 125 levels in a normal population, phase I: the specificities of single and serial determinations in testing for ovarian cancer. AB - To determine the potential efficacy of the CA 125 assay as one component of a strategy for early detection of ovarian malignancy, serum CA 125 levels were determined in 1082 women 40 years of age or older in Stockholm. Initial serum CA 125 levels exceeded 35 U/ml in 36 women (3.3%) and 65 U/ml in 11 women (1.0%), placing the exact 95% upper confidence limits on false positive rates for a single screen at 4.3 and 1.7%, respectively. Follow-up CA 125 levels were obtained for those women with initially elevated levels and a group of age matched controls. Mean CA 125 levels declined significantly for women with initially elevated levels (P = 0.0014). Interindividual variation and variation within individual subjects over the entire follow-up period were 52 and 35%, respectively. Of the 36 subjects with initially elevated serum CA 125 levels, only 2 showed a doubling of these levels; in only 1 of these 2 was this increase sustained. Intensive clinical follow-up with pelvic examination and ultrasonography, with investigators blinded to CA 125 results, led to the diagnosis of Stage III ovarian cancer in the latter individual. Diagnosis was made 21 months after the initially elevated serum CA 125 measurement and 15 months after the first measured doubling of that level. Because no other malignancies were identified at entry or during the follow-up period (median 560 days) in the women with elevated CA 125 levels, the specificity of the assay over that time period would have been 99.9% using the doubling of an initially elevated value as the criterion for determining positivity and 100% using as the criterion a sustained increase in level for those with initially elevated levels that doubled. These results support the continued investigation of longitudinally collected CA 125 levels to identify individuals at high risk for ovarian malignancy. PMID- 2318439 TI - Endocervical curettage by Vabra aspiration as part of colposcopic evaluation. AB - Endocervical curettage as routine part of colposcopic examination in patients with abnormal cervical cytology is recommended by many experts. Endocervical curettage (ECC) by Vabra aspiration has never been reported in literature. The results of Vabra ECC in 103 patients are analyzed and compared to the results of a second endocervical specimen, obtained by conventional curettage, cone biopsy, or hysterectomy. An accordance of over 98% is demonstrated and the difference is discussed. In 88% and 71% adequate Vabra ECC specimens were available for cytological and histological examination, respectively. In any patient at least one result was present. Both cytological and histological specimens are of reliable quality. No cases of invasive (adeno)carcinoma were missed. In addition, the results are compared to literature data concerning Vabra aspiration for endometrial disease and ECC by other techniques. Vabra ECC is considered an efficient, safe, and well-tolerated diagnostic outpatient method and recommended as a standard part of colposcopic evaluation. PMID- 2318440 TI - Salvage whole-abdominal irradiation following chemotherapy failure in epithelial ovarian carcinoma. AB - During the period 1977 to 1985, 12 patients with FIGO stage II and III epithelial ovarian carcinoma failed to achieve a pathologic complete response with chemotherapy and underwent salvage whole-abdominal irradiation (WAXRT). Six of these patients had gross residual disease present at the time of irradiation, and three (50%) were unable to complete the planned radiotherapy. All eventually failed in the treatment field; their 5-year actuarial survival and local control rates were zero. The other six were irradiated without residual macroscopic disease. Five of the six (83%) were able to complete WAXRT as planned without prolonged delays. The 5-year actuarial survival and local control rates for this group were 21 and 25%, respectively. The actuarial laparotomy rate to relieve bowel obstruction following WAXRT was 40% at 2 years. The results from this and other series indicate that salvage WAXRT is not effective for patients irradiated with macroscopic tumor. However, WAXRT appears to be potentially curative for a small but significant percentage of patients irradiated without gross disease, although the risk of significant complications is high. PMID- 2318441 TI - Serial measurement of CA 125 in patients with primary carcinoma of the fallopian tube. AB - Serial assay of serum CA 125 was carried out in five patients with advanced primary carcinoma of the fallopian tube. Pretreatmental levels of these patients were elevated, ranging from 145 to 535 U/ml (305 +/- 140.1, mean +/- SD). All patients showed rapid decreases in response to treatment; however, reelevations were noted in two patients concomitant with recurrence. In the remaining three patients, who are alive with no evidence of recurrence at 52, 29, and 21 months, serum CA 125 levels remained below 5 U/ml after remission. These results suggest that CA 125 is useful in monitoring patients with primary carcinoma of the fallopian tube. PMID- 2318442 TI - Whole-abdominal radiotherapy for patients with minimal residual epithelial ovarian cancer. AB - Sixteen patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery followed by multiagent chemotherapy were found to have residual tumor masses less than 2 cm in greatest diameter at reexploration and were treated with whole-abdominal radiation (19-31 Gy). Thirteen patients also received pelvic boosts to a total pelvic dose of 41-53.7 Gy. Radiotherapy was completed in all but 2 patients after treatment delays in 7 patients. Early treatment complications included myelosuppression in 11 patients, diarrhea in 3, and a self-limited small bowel obstruction in one. Delayed complications were severe and included 9 patients with radiation enterocolitis, 8 of whom required intestinal resection or diversion. One additional patient with radiation cystitis required instillation of formalin to control bleeding. Two patients are without evidence of disease 28 and 30 months following radiotherapy, while the remaining 14 patients have recurred after a median progression-free interval of 9 months (range 1-30 months). All patients who recurred failed within the treatment field and died of cancer after a median interval of 19 months following radiotherapy and 9 months after documentation of progression. These data suggest that few patients with persistent ovarian cancer following surgery and chemotherapy will be salvaged with radiotherapy. PMID- 2318443 TI - Morbidity and survival patterns in patients after radical hysterectomy and postoperative adjuvant pelvic radiotherapy. AB - Morbidity and survival patterns were reviewed in 50 patients who underwent radical hysterectomy, pelvic lymphadenectomy, and adjuvant postoperative pelvic radiotherapy for invasive cervical cancer. Ninety percent of the patients were FIGO stage IB, and 10% were clinical stage IIA or IIB. Indications for adjuvant radiotherapy included pelvic lymph node metastasis, large volume, deep stromal penetration, lower uterine segment involvement, or capillary space involvement. Seventy-two percent of the patients had multiple high-risk factors. An average of 4700 cGy of whole-pelvis radiotherapy was administered. Ten percent of the patients suffered major gastrointestinal complications, 14% minor gastrointestinal morbidity, 12% minor genitourinary complications, one patient a lymphocyst, and one patient lymphedema. Of the five patients with major gastrointestinal morbidity, all occurred within 12 months of treatment. Three patients required intestinal bypass surgery for distal ileal obstructions and all are currently doing well and free of disease. All of the patients who developed recurrent disease had multiple, high-risk factors. The median time of recurrence was 12 months. All patients recurred within the radiated field. Actuarial survival was 90% and disease-free survival 87% at 70 months. It is our opinion that the morbidity of postoperative pelvic radiotherapy is acceptable, and benefit may be gained in such a high-risk patient population. PMID- 2318444 TI - Use of local flaps for primary anal reconstruction following perianal resection for neoplasia. AB - Perianal resection for neoplasia is associated with a significant risk for subsequent fecal incontinence. This report describes primary reconstruction of the anus using local skin flaps in nine patients who had undergone resection of perianal tissue for neoplasia. Seven patients had invasive cancer, and two patients had carcinoma in situ with a preoperative suspicion of invasive cancer. In all nine patients a portion of the external anal sphincter was excised during surgery. Bilateral rhomboid flaps were used in five patients, and four patients had advancement of local full-thickness skin flaps. All nine patients had a satisfactory anatomic result and were ultimately fecally continent. PMID- 2318445 TI - Estrogen and progesterone receptor content of endometrial carcinomas: comparison of total tissue versus cancer component analysis. AB - Estrogen (ER) and progesterone (PgR) receptor values in 105 endometrial carcinomas were compared using immunocytochemical and standard biochemical techniques. Peroxidase-antiperoxidase staining for location of anti-ER (H222) and anti-PgR (JZB39) primary antibodies was used to generate a semiquantitative (HSCORE) assessment of receptor content in tissue components and the total specimen. Both total HSCORE and cancer component HSCORE correlated with log biochemical assay values for ER and PgR. Biochemical assay values, total HSCORE, and cancer component HSCORES all demonstrated internal correlations between ER and PgR levels. Correlation was somewhat closer for cancer component HSCORE values of ER and PgR than the values for total tissue HSCORE. When receptor content was analyzed by histologic grade, all three estimates of receptor status demonstrated a decreasing proportion of ER and PgR positive lesions with decreasing histologic differentiation; however, the proportion of receptor negative lesions in grade 3 lesions was much higher when using total HSCORE or cancer component HSCORE than when using biochemical assay values (P less than 0.005. Immunocytochemical techniques for localization of ER and PgR in endometrial carcinoma specimens may allow a more focused evaluation of the receptor content in the malignant elements than standard biochemical techniques. PMID- 2318446 TI - Phase II clinical trial of VP-16-213 (etoposide) administered orally in advanced ovarian cancer. AB - Antitumor effect and toxicity of single-drug treatment with per oral VP-16-213 (etoposide) were evaluated in a phase II trial which included 22 patients with recurrence or progression of ovarian carcinoma. Two of these patients were evaluable only for toxicity. All patients had previously been treated with a combination chemotherapy involving at least three different drugs. The median age was 59 years (range 21-76). VP-16-213 was administered orally at a daily dose of 200 mg/m2 for 4 consecutive days every third week with systematic dose escalation. Fourteen patients were treated to grade 3-4 hematologic toxicity (WHO) and 8 to grade 0-2. Eleven experienced nausea and vomiting and 4 partial alopecia. One patient achieved a CR and another a PR with a duration of 3 months and 5 + months, respectively. PMID- 2318447 TI - Superficially invasive carcinoma of the vagina following treatment for cervical cancer: a report of six cases. AB - Six patients with superficially invasive squamous carcinoma of the vagina are described. All patients meet recently proposed criteria for the diagnosis of microinvasive vaginal carcinoma. The depth of invasion measured from the surface was less than 2.5 mm. There was no lymph-vascular space involvement. The invasive foci arose within a field of carcinoma in situ. Five of these six patients had previously been treated for invasive cervical cancer with pelvic radiation from 82 to 246 months before the diagnosis of vaginal carcinoma. All but one patient had the carcinoma confined to the upper one-third of the vagina. All patients were treated with a single vaginal radium application following vaginectomy. One of these six patients expired from recurrent vaginal cancer 35 months following diagnosis. During the same 17-year period, 17 other cases of Stage I epidermoid cancer of the vagina were treated which did not meet the above criteria for microinvasion. There were no statistically significant differences between these two groups with regard to age at diagnosis, history of cervical cancer, hysterectomy, or pelvic radiation or in survival. Additional experience with early vaginal carcinoma is needed before microinvasive carcinoma of the vagina should be accepted as a distinct clinical entity. PMID- 2318448 TI - Pelvic hemangiopericytomas: a report of five cases and literature review. AB - Five cases of pelvic hemangiopericytomas are reported. One of these tumors arose from the uterus, and four patients had extrauterine, pelvic hemangiopericytomas. The patient with a primary uterine hemangiopericytomas had only simple excision, and, after 6 years, is alive and free of disease. All four patients with extrauterine, pelvic hemangiopericytomas had incomplete resection of their tumors because of hemorrhage. However, pelvic radiation therapy was then employed in these patients and produced a complete regression in one patient and partial regression in two patients with minimal shrinkage in another patient. The latter patients were reexplored after pelvic radiation and underwent complete resection of their disease. Two patients developed pelvic recurrences at 2 and 9 years, respectively, and these were effectively resected. All four patients are all alive and free of disease 5 to 18 years later. If this lesion is unexpectedly discovered at laparotomy, our experience suggests that the resection should be discontinued and that they should be treated with pelvic radiation and delayed resection of persistent and recurrent pelvic tumors. PMID- 2318449 TI - Urinary gonadotropin fragment, a new tumor marker. I. Assay development and cancer specificity. AB - Urinary gonadotropin fragment (synonyms: UGF and human chorionic gonadotropin beta-subunit core fragment) is a small peptide which is present in the urines of pregnant women, of those with trophoblast disease and of those with certain nontrophoblastic malignancies. We developed a new UGF assay with improved specificity and then investigated levels in urines of 493 women: 155 healthy and postmenopause, 79 healthy and premenopause, 89 with benign gynecologic disease, and 170 with active gynecological cancer. A UGF cutoff level of greater than 3 fmole/ml was chosen to monitor the progress of patients during and after cancer therapy. Using this cutoff value, UGF specificity and sensitivity for active cancer were 90 and 66%, respectively. Levels exceeded this cutoff in 74% of women with recurrent disease. For screening purposes and for differentiating benign and malignant disease a cut-off of 8 fmol/ml, was indicated. At this higher cutoff specificity and sensitivity for active cancer were 99 and 46%, respectively. PMID- 2318450 TI - Urinary gonadotropin fragment, a new tumor marker. II. Differentiating a benign from a malignant pelvic mass. AB - We examined the efficacy of CA125 and urinary gonadotropin fragment (UGF) measurements for differentiating benign from malignant pelvic masses. CA125, at a cutoff of greater than or equal to 35 U/ml, detected 82% (n = 71) of ovarian malignancies, but also falsely detected 14% of (n = 332) patients with benign pelvic masses. When the CA125 cutoff was raised from greater than or equal to 35 to greater than or equal to 200 U/ml, the number of false-positives decreased to 1.2%, a manageable level. However, using greater than or equal to 200 U/ml only 49% of cancers were detected. We examined levels of UGF and found that they complement those of CA125, detecting false-negatives. Using UGF at a cutoff of greater than 8 fmol/ml and CA125 at greater than or equal to 200 U/ml a combined sensitivity of 86% was achieved for malignant pelvic masses, with minimal false detection of benign disease (less than 1.2%). We propose that parallel measurements of CA125 and UGF should be used for discriminating benign and malignant pelvic masses. PMID- 2318451 TI - Cancer-related maternal mortality in Massachusetts, 1954-1985. AB - Cancer-related maternal mortality is a rare event. We report the first population based study of this issue using data collected by the Committee on Maternal Welfare of the Massachusetts Medical Society between 1954 and 1985. The incidence of cancer-related maternal mortality during the study period fell from 3.16 to 0 per 100,000 live births. The most common cancer-associated maternal deaths were due to central nervous system tumors and hematological cancers. To determine the effects of pregnancy on cancer mortality, we compared our data with figures from the Connecticut Register of Mortality for Women aged 15-44. In the pregnant group there was a significantly higher incidence of mortality due to central nervous system tumors and a significantly lower incidence of mortality due to breast cancer. The data suggest that pregnancy may not be contraindicated for a woman with a history of breast cancer, but may be contraindicated for a woman with a history of a central nervous system tumor. PMID- 2318452 TI - Hysterectomy with extended surgical staging and radiotherapy versus hysterectomy alone and radiotherapy in stage I endometrial cancer: a comparison of complication rates. AB - Extended surgical staging (ESS) has been added to total hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) in patients with clinical Stage I endometrial cancer in order to better define patterns of metastatic spread and the response to treatment. Adjuvant radiotherapy has a demonstrated efficacy in decreasing central recurrence in Stage I disease. The combined use of radical surgery and pelvic radiotherapy for cervical cancer patients results in an increased incidence of complications. This study compares major complication rates in Stage I endometrial cancer patients who underwent either TAHBSO with ESS or TAHBSO alone followed by adjuvant external beam radiotherapy (RT). Records of 52 patients with clinical stage I endometrial cancer were reviewed. Thirty-two patients underwent TAHBSO plus ESS and 20 patients had TAHBSO alone. All patients received postoperative, whole pelvis external radiotherapy. Four patients suffered complications potentially related to treatment which required rehospitalization, and all 4 were in the group which had undergone ESS. A comparison of complication rates between the ESS + RT group (4/37 or 10.8%) and TAHBSO + RT group (0/20) suggested a trend toward significance (P less than 0.10). Treatment protocols using extended surgical staging prior to adjuvant radiotherapy in Stage I endometrial cancer should examine complications potentially related to this combination, to further define treatment risks and benefits. PMID- 2318453 TI - Symptomatic central venous thrombosis and long-term right atrial catheters. AB - The use of long-term right atrial access catheters is increasing due to their value as aids in the administration of chemotherapy and hyperalimentation. A rare complication of catheter use is subclavian vein thrombosis. Suspicion of subclavian venous thrombosis based on clinical findings should be confirmed by venography. Therapy should be individualized, but may include antibiotics, catheter removal, thrombolytics, and anticoagulants. Resolution of symptoms is the usual outcome, but this may be influenced by other compounding factors. PMID- 2318454 TI - A comparative study of computerized tomography, magnetic resonance imaging, and clinical staging for the detection of early cervix cancer. AB - Sixteen patients with cervical cancer underwent radical surgery following standard clinical staging, MRI, and CT. The sensitivity of the CT scan was 14%, the specificity 100%. MRI had a sensitivity of 28% and a specificity of 64%. The clinical stage was correct in 10 of 16 patients (62%). CT and MRI are not individually or collectively better than clinical staging in predicting extent of disease, and currently should not be included in the FIGO staging for cervix cancer. PMID- 2318455 TI - Radioimmunodetection of uterine leiomyosarcoma with 111In-labeled monoclonal antimyosin antibody Fab fragments. AB - Radioimmunodetection of uterine leiomyosarcoma in a 64-year-old woman with a palpable local recurrence is described. Pathological abdominal, pelvic, and thoracic accumulation of monoclonal 111In-labeled antimyosin was observed. Afterward, these lesions were examined by whole-body X-ray computed tomography. With a double-tracer technique (pulmonary and hepatic/splenic subtractions) the lesions were delineated better and SPECT (radioisotope tomography) was used for more accurate localization of the abdominal and pelvic lesions. These findings indicate that antimyosin scintigraphy might be useful in staging and follow-up of uterine leiomyosarcoma. PMID- 2318456 TI - High-grade pelvic sarcoma after radiation therapy for low-grade endometrial stromal sarcoma. AB - A high-grade heterologous pelvic sarcoma arose in a 60-year-old woman 15 years after she received whole-pelvic radiation for a low-grade endometrial stromal sarcoma. This complication must be considered in determining therapy for low grade endometrial sarcomas, which are usually inherently of indolent biological behavior. PMID- 2318457 TI - Rapidly progressing cervical cancer in a patient with human immunodeficiency virus infection. AB - Many malignancies occur in association with the acquired immunodeficiency syndrome (AIDS). The incidence of cervical intraepithelial neoplasia is increased in patients with human immunodeficiency virus (HIV) infection, although coexistent HIV infection and cervical cancer have not been described. We describe a patient with HIV infection and a stage IIB, poorly differentiated cervical carcinoma who initially responded well to standard radiation therapy. Relapse at an unusual periclitoral site as well as disseminated carcinomatosis appeared within 2 months. Despite chemotherapy with cisplatin, bleomycin, and mitomycin C, the patient died within 3 months of relapse. This pattern of aggressive tumor behavior may occur more frequently as HIV infection spreads into the heterosexual population. We recommend frequent pelvic and cytologic examinations of HIV infected women and the consideration of an aggressive treatment approach should invasive carcinoma be detected. PMID- 2318459 TI - National health line. PMID- 2318458 TI - Cervical cancers in uterus didelphys. AB - Two cases of cervical cancer in uterus didelphys are presented. One was extensive adenocarcinoma and one was squamous cell carcinoma in situ. In both cases the cancers appeared to have originated separately in each cervix. PMID- 2318460 TI - Policies to enhance coordination in hospital-based case management programs. AB - Social work practitioners in health and social services are expected to develop and implement programs and client care plans that require cooperation and coordination with numerous other individuals and programs. Such cooperation and coordination often are accomplished through informal networking. As programs develop, these relationships may be formalized in written policy agreements. In this article, the authors examine four policies designed to improve cooperation and coordination at different levels in hospital-based case management systems. Implications for social work practice are discussed. PMID- 2318461 TI - Social work management in emerging health care systems. AB - An overview of the health care industry's trend toward multihealth systems is presented and specific adaptive strategies for social work managers in health care are suggested. The challenges to social work leaders during this transition from largely free-standing, privately owned health care institutions to corporately owned, horizontally and vertically integrated delivery systems are discussed in terms of identity, style, and substance. Directors of social work departments in multihealth corporations will need to resolve issues of institutional versus corporate identity as well as those of corporate versus professional identity. A multioptional management style that incorporates networking and political expertise should be cultivated. Substantive demands in the areas of management information systems, productivity, quality assurance, and budgeting also must be addressed. The emergence of multihealth systems poses major challenges and unique opportunities to the social work profession. Awareness of managerial strategies and critical content areas can help social work leaders enhance the role and contribution of social work in these exciting and complex health care delivery systems. PMID- 2318462 TI - Group work in a primary care medical setting. AB - A group work program was developed for low-income, minority patients of a primary care medical setting who were misusing medical resources to work on psychosocial issues. Multiple groups were established using an action-oriented approach to enhance patients' ability to cope with health, mental health, and environmental problems. The program was demonstrated to be beneficial for the participants and the primary care clinic. PMID- 2318463 TI - Autonomy and professional activities of social workers in hospital and primary health care settings. AB - Social workers in hospital settings often experience frustration working in the host setting of a hospital. Some hospital social workers may consider a move to a private primary health care setting to gain more autonomy on the job and the opportunity to provide more direct clinical services and less task-oriented ones. In this article, the authors report a study that compared the autonomy and professional activities of social workers in hospital settings and private primary care settings. It was found that social workers in the two settings do not differ in their level of perceived autonomy and that those in private primary care provide more therapy and counseling. The implications of these and other findings are discussed. PMID- 2318464 TI - Hospital graduate social work field work programs: a study in New York City. AB - Twenty-seven hospital field work programs in New York City were studied. Questionnaires were administered to program coordinators and 238 graduate social work students participating in study programs. High degrees of program structural complexity and variation were found, indicating a state of art well beyond that described in the general field work literature. High rates of student satisfaction with learning, field instructors, programs, and the overall field work experience found suggest that the complexity of study programs may be more effective than traditional field work models. Statistically nonsignificant study findings indicate areas in which hospital social work departments may develop field work programs consistent with shifting organizational needs, without undue risk to educational effectiveness. Statistically significant findings suggest areas in which inflexibility in program design may be more beneficial in the diagnostic related groups era. PMID- 2318465 TI - Targeted adolescent pregnancy substance abuse project. PMID- 2318466 TI - Maintaining social work standards in for-profit hospitals. PMID- 2318467 TI - Vertebral artery rupture in traumatic subarachnoid haemorrhage detected by postmortem angiography. AB - A fatal subarachnoid haemorrhage from a ruptured normal intracranial vertebral artery in a 49-year-old male, following a blow to the head, was revealed by a postmortem angiographic technique using radiopaque silicone rubber as a contrast medium vulcanizing at room temperature. No fracture of the atlas or connection between intracranial vessels and extracranial soft tissue haematoma could be visualized. We advocate the use of postmortem angiography in the diagnosis of suspected head trauma sustained in fights. PMID- 2318468 TI - Post mortem kinetics of secobarbital. AB - Post-mortem changes in barbiturate concentrations were evidenced using a rat secobarbital model. The method used for the extraction and HPLC assay of barbiturates is suitable for all biologic fluids and post-mortem tissues. Kinetic data obtained is of excellent quality. Various modelization constants were defined. This experimental work emphasizes the difficulty of post-mortem toxicology, as concentrations found at the time of autopsy may be different from concentrations at the time of death, in blood as well as in tissues. PMID- 2318469 TI - Double logarithmic, linear relationship between plasma sodium/potassium concentration ratio and postmortem interval during the 6-96-h postmortem period in rats. AB - Flame photometric determination of sodium and potassium concentrations in postmortem rat plasma (n = 40) revealed the existence of a linear and inverse relationship, of high correlation (r = -0.986; P less than 0.001), between the logarithm of the plasma sodium/potassium concentration ratio (PNa/PK) and the logarithm of postmortem interval (PMI) during the 6-96-h postmortem period. This relationship, which has not been reported previously in the forensic literature, offers a simple and potentially valuable means of estimating the PMI in man. PMID- 2318470 TI - Histological examination of the temporal bone in medicolegal cases of asphyxia. AB - Histological findings of the temporal bone in 23 autopsy cases of various asphyxial fatalities were studied. The temporal bones of 12 cases who died of tumors including mammary cancer, gastric cancer, myxoma of heart and craniopharyngioma, the bones of 3 cases of heart attack and the bones of 17 cases who died of various poisoning (barbiturate, amphetamine, paraquat and alcohol) were used as controls. In drowning, the primary finding was hemorrhage in the mastoid air cells of the bilateral temporal bones. In cases of strangulation by ligature, hemorrhage and edema of the cochlear duct in the inner ear as well as hemorrhage in the mastoid air cells were demonstrated bilaterally. In contrast, congestion and edema in the mastoid air cells and inner ear were found in cases of manual strangulation but there was no hemorrhage. From these results, the histological examination of the temporal bone is useful as an adjunct procedure for diagnosing the cause of asphyxia. Differentiation between drowning, strangulation by ligature and manual strangulation may be possible by observing hemorrhages or their absence in the mastoid air cells and inner ear. PMID- 2318471 TI - The course of respiration and circulation in 'toluene-sniffing'. AB - To investigate the course of respiration and circulation in death by toluene inhalation, 25 dogs were allowed to rebreathe toluene vapor in a 1-1 plastic bag expanded with air, and electrocardiogram (ECG), electroencephalogram (EEG), blood pressure (BP) in the femoral artery and intrathoracic pressure (ITP) were registered. The respiratory movement continued two times longer than that of death by suffocation using a plastic bag of the same size. In the ECG, low voltage of R waves precipitously appeared several minutes after the beginning of the experiment and continued. The BP gradually reduced by half and kept the level for several minutes. The stage was considered toluene narcosis. Toward the end of the respiratory movement, the BP increased gradually. The analysis of the ECG complexes during the toluene inhalation revealed the direct effect of toluene to the septal and ventricular muscle of the heart. But in the end of the respiratory movement, it revealed ST segment elevation and upright T. In a few experimental animals, some of the transient arrhythmia with fluctuation of the BP appeared during the course, and in one of these dogs, fatal ventricular fibrillation occurred suddenly. These findings suggested that in most cases of sudden death in 'toluene-sniffing', the cause of death is severe hypoxia during toluene narcosis, but in a few cases, it is fatal arrhythmia due to the direct effect of toluene to the heart muscle. PMID- 2318472 TI - The stability of several compounds in formalin fixed tissues and formalin-blood solutions. AB - Buffered formalin solutions were added to spiked blood samples containing diazepam, phenytoin, carbon monoxide and cyanide to give formalin-whole blood solutions of 5 and 8%. Sections of liver positive for desipramine, phenobarbital and phenytoin were placed in separate 5 and 8% formalin-water solutions. The formalin-blood solutions were monitored daily for 30 days, while the fixed liver and formalin-water samples were analyzed once a week for 4 weeks. In the formalin blood solutions losses were found for diazepam and phenytoin over the 30-day period of at least 41% and 33%, respectively. Cyanide detection was not possible immediately after the addition of formalin and the presence of carboxyhemoglobin was difficult to detect after 1 week. In the liver, losses of phenobarbital and desipramine were greater than 60% while phenytoin showed little change. This study has revealed that the drugs examined at toxic concentrations can be detected, with variable recoveries, for up to 30 days after fixation with formalin. However, quantitative analysis for cyanide and carboxyhemoglobin may be significantly impaired in the presence of formaldehyde. PMID- 2318473 TI - Correlation between 'on admission' blood toluene concentrations and the presence or absence of signs and symptoms in solvent abusers. AB - For 1 year, from June 1987 to June 1988, toluene concentrations in blood samples of patients admitted to a psychiatric hospital after inhaling solvent vapor, collected on admission and 4 h later, were analyzed by gas chromatograph. Toluene levels in the first urine samples collected after admission were also analyzed and case histories were kept listing age, sex and physical and psychiatric effects. In all, 51 cases were studied--34 males and 17 females. (1) The average age of the males was 21.4 years and of the female 16.2 years. (2) The toluene concentrations in the blood collected on admission ranged from 0.3 to 22.8 micrograms/g. (3) Physical signs were observed in 9 patients with an "on admission" blood toluene concentrations of more than 3.0 micrograms/g; twice as many subjects (18), however, with blood toluene concentration greater than 3.0 micrograms/g were without physical signs. (4) The blood toluene concentrations of three cases in the condition known as twilight state were more than 10.0 micrograms/g. (5) In 24 cases with blood toluene concentrations below 3.0 micrograms/g, there were no physical signs. (6) Five subjects with blood toluene concentrations in the 0.8-5.2 micrograms/g range showed neuropsychiatric effects; however, 23 subjects in the same blood toluene concentration range did not exhibit psychiatric effects, and none of the subjects with blood toluene concentrations greater than 5.2 micrograms/g, 15 in all, had such effects. PMID- 2318474 TI - Enzyme-linked immunoabsorbent assay for plasma thyroglobulin following compression of the neck. AB - A highly sensitive enzyme-linked immunosorbent assay (ELISA) for determination of plasma thyroglobulin (Tg) which we devised was applied to the postmortem diagnosis of external compression of the neck. The coefficients of variation within and between assays were 2.4-6.6% and 6.8-12.0%, respectively. A significant correlation was observed between Tg levels measured by our ELISA and those measured by radioimmunoassay (r = 0.996, P less than 0.001). Plasma Tg levels in all 36 cadavers without external compression of the neck or neck injuries were lower than 200 ng/ml (73.6 +/- 51.9 ng/ml, M +/- S.D.) although these levels were a little higher than those in living bodies (16.7 +/- 11.8 ng/ml). On the other hand, plasma Tg levels in most of 42 victims of asphyxia due to external compression of the neck were higher than 200 ng/ml (2190 +/- 4300 ng/ml), and the highest one was 24,600 ng/ml. Plasma levels of the other thyroid hormones and thyroid-stimulating hormone were determined in some cases, and the cervical conditions in certain cases of strangulation were analyzed. Present results suggest that Tg was released by mechanical force on the thyroid gland added at the agonal stage. The determination of plasma Tg level in a cadaver using our ELISA would seem to be useful for the postmortem diagnosis of the presence of external compression of the neck. Although thyroid diseases causing elevated Tg levels are rare in forensic cases, they should be excluded by routine histology of the thyroid at autopsy, so that the finding of a high Tg level would thus carry more weight when given in evidence. PMID- 2318475 TI - Typing study of human semen DIA3 by isoelectric focusing--distribution in the Wuhan population, China. AB - Human semen DIA3 typing was studied by isoelectric focusing on ultra-thin-layer polyacrylamide gel which resulted in a simpler and more definite separation of the products of DIA3 alleles than hitherto. In 198 semen samples collected from unrelated Chinese males four different phenotypes were observed. The DIA3 allele frequencies were calculated: DIA 3(1) = 0.7727, DIA 3(2) = 0.2172, DIA 3(3) = 0.0101. The results of the stability study of 12 laboratory-prepared semen stains stored at room temperature suggested that DIA3 in seminal strains is a relatively stable genetic marker. Our gene frequencies have been compared to those reported in other populations. PMID- 2318476 TI - Isotachophoretic determination of lactate ions in vitreous humour samples and its use in forensic toxicology. AB - Isotachophoresis has been successfully used to determine the lactate ion concentrations in 40 vitreous humour samples taken from subjects representative of those normally encountered by the forensic pathologist. The method is described, and the use of the analysis in forensic toxicology is discussed. PMID- 2318477 TI - Positive- and negative-ion mass spectrometry and rapid clean-up of 19 phenothiazines. AB - Positive-ion electron impact (PIEI), positive-ion chemical ionization (PICI) and negative-ion chemical ionization (NICI) mass spectra of 19 phenothiazines are presented. In the PIEI mode, peaks due to M, M minus side chain (M - R1), M - R1 + H, and side chain itself (R1) appeared for most compounds. The M - R1 and R1 ions were very useful for drug screening. In the PICI mode, most spectra showed base or intense peaks due to M + H, and small peaks due to M + C2H5; peaks due to M - R1 + 2H and R1 also appeared in many compounds. In the NICI mode, fragmentation modes were different in different compound groups; molecular or [M H]- quasi-molecular anions appeared in many compounds with aliphatic side chains. Anions at m/z 98 and 115 were characteristic for compounds with (N methylpiperazinyl)propyl side chains. Selected ion monitoring in the PIEI mode generally gave much higher sensitivity than in the PICI and NICI modes. Phenothiazines present in urine or plasma could be rapidly isolated by use of Sep Pak C18 cartridges. Thirteen of 19 phenothiazines could be detected by HP-17 wide bore capillary gas chromatography with satisfactory separation from impurities in their underivatized forms. PMID- 2318478 TI - [Children with dyspnea. A comprehensive treatment concept in obstructive respiratory tract diseases. Abstracts of a Boehringer Ingelheim KG Therapy Forum. 27-29 October 1989, Bad Nauheim]. PMID- 2318479 TI - [Practical procedures in chronic obstructive respiratory tract disease in children]. PMID- 2318480 TI - Surfactant-associated glycoproteins accumulate in alveolar cells and secretions during reparative stage of hyaline membrane disease. AB - Surfactant-associated (SA) glycoproteins are lung-specific proteins produced in the human lung by alveolar type II cells and Clara cells. The distribution of these proteins was studied immunohistochemically in lung tissue obtained postmortem from 12 stillborn fetuses and 49 infants with hyaline membrane disease (HMD). By 21 weeks of gestation, SA glycoproteins were detected in the fetal alveolar epithelium and within Clara cells. The staining increased in intensity and extent with advancing gestational age. Infants with HMD who survived less than 48 hours did not generally exhibit stainable material either within type II cells or secretions, but staining was often noted in Clara cells as well as focally beneath hyaline membranes. In infants surviving more than 48 hours, intense staining of hyaline membranes, alveolar secretions, proliferating alveolar type II cells, and Clara cells was evident. Immunoreactivity was intense in hypertrophic type II cells that formed a continuous alveolar epithelial lining in lungs with bronchopulmonary dysplasia. Included in the population of infants with HMD were 15 infants with pulmonary hypoplasia. The lungs of these infants showed minimal staining for SA glycoproteins regardless of postnatal survival time. The results provide an immunomorphologic basis for defining normal and abnormal lung maturation. They also indicate that enhanced SA glycoprotein production is a sustained response of regenerating and hypertrophic type II cells in premature infants. PMID- 2318481 TI - Ovarian serous borderline tumors with stromal microinvasion: a report of 21 cases. AB - The clinicopathologic features of 21 cases of otherwise typical serous borderline tumors that contained small foci of stromal invasion were reviewed. The mean age of the patients was 43 years and six of them were pregnant at the time of diagnosis. Nineteen tumors were stage I, one was stage III (para-aortic lymph node involvement) and one was stage IV (parenchymal liver metastasis). The tumor invaded the stroma predominantly as individual cells or nests or clusters of cells with abundant eosinophilic cytoplasm (17 cases), as small confluent nests with a cribriform pattern (two cases) and as rounded aggregates of papillae (two cases). Seven women were treated with bilateral salpingo-oophorectomy and hysterectomy; 13 had less than bilateral oophorectomy. Of the 17 patients for whom followup data were available, 16 were without evidence of disease 1 to 11 (mean, 5.2) years postoperatively, and one patient had a serous borderline tumor with microinvasion in a conserved contralateral ovary 2.8 years postoperatively, but was well 6 months after a partial oophorectomy. These data suggest that serous borderline tumors with microinvasion have a prognosis similar to that of the usual serous borderline tumor, and that conservation of the contralateral ovary and uterus may be acceptable therapy in young women who wish to preserve their fertility. PMID- 2318482 TI - The prognostic significance of selective nuclear morphometry in urinary bladder carcinoma. AB - Transurethral resected tumor specimens of 61 patients with a primary and untreated bladder carcinoma were studied by selective nuclear morphometry, a method recently described by us. A significant enlargement of the mean nuclear area was found with the advance of tumor grade and stage (Wilcoxon, P less than .0001 and P less than .0001). The heterogeneity of the grade 2 patient group and the additional value of morphometry were demonstrated by observing the 5-year survival rates. Patients with grade 2 carcinoma could be separated into one subgroup with small nuclei (mean nuclear area less than or equal to 95 microns2) having a favorable outcome (5-year survival rate: 100%), and into another subgroup with large nuclei (mean nuclear area greater than 95 microns2) showing a worse prognosis (5-year survival rate: 63.2%) (Mantel-Cox, P = .01). The outcome of these subgroups was not significantly different from that of the grade 1 (5 year survival rate: 93.8%) and grade 3 (5-year survival rate: 50%) patients, respectively (Mantel-Cox, P = .45 and P = .57). The value of selective nuclear morphometry, in addition to tumor staging, was indicated by the association of nuclear enlargement (mean nuclear area greater than 95 microns2) with progressive recurrence (five of 15 patients; 33%) among the patients with conservatively treated superficial carcinoma (stages Ta and Tl). The findings demonstrate the supplementary value of selective nuclear morphometry to tumor grading and staging, especially in the heterogeneous group of grade 2 carcinomas and the group of superficial tumors (stages Ta and Tl). PMID- 2318483 TI - Soft-tissue and meningeal hemangiopericytomas: an immunohistochemical and ultrastructural study. AB - The debate on the nosologic position of hemangiopericytomas of the meninges has been based mainly on light microscopic and ultrastructural considerations; recent immunohistochemical studies have yielded controversial results. We have used a panel of antibodies to vimentin, desmin, actin, S100 protein, epithelial membrane antigen, cytokeratins, Leu-7, factor VIII-related antigen and type IV collagen to compare the immunophenotype of 10 soft-tissue and seven meningeal hemangiopericytomas. The immunophenotypic profile of these tumors is identical, and differs from that of meningiomas in that epithelial membrane antigen and cytokeratin are not present. The vascular pattern occurring in some meningiomas can simulate true hemangiopericytomas of the meninges. Immunohistochemical studies should allow their distinction in each instance. Meningeal and soft tissue hemangiopericytomas display similar ultrastructural features. PMID- 2318485 TI - Diversion colitis: a clinicopathologic study of 21 cases. AB - Inflammation occurring in a defunctionalized portion of bowel, following either ileostomy or colostomy, has long been recognized by endoscopists. However, little has been written about this entity, particularly the histopathologic changes. Glotzer et al in 1981 described 10 cases, and coined the term "diversion colitis". We studied 21 patients without previous history of inflammatory bowel disease who, for reasons including perforated diverticulitis, carcinoma, or trauma, had loop colostomies or Hartmann's procedure performed. Many of these patients became symptomatic with complaints related to the defunctionalized bowel, including rectal discomfort, pain, discharge, and bleeding. Nineteen patients had endoscopic examinations, which revealed a variety of findings including mucous plugs, friability, petechia, erythema, ulcers, exudate, and nodules or polyps. All except one case had tissue from the excluded portions of bowel available for pathologic examination. Most displayed nonspecific changes with mild-to-moderate lymphoplasmacytic infiltrates in the lamina propria, mild architectural alterations of the crypts, and slight decrease in crypt numbers. Ulceration, cryptitis, and crypt abscesses simulating ulcerative colitis were uncommon findings and were observed almost exclusively in more severe cases. Granulomas were observed in two cases, raising the possibility of Crohn's disease. PMID- 2318484 TI - Collagen profile in the transplanted heart. AB - To substantiate the finding of interstitial myocardial fibrosis in the transplanted heart and to characterize the collagen profile of the transplanted heart, we studied endomyocardial biopsy specimens from 30 heart transplants and four heart-lung transplants at 1 to 82 months after transplantation. Indirect immunofluorescent techniques with affinity-purified antibodies for collagen types I, III, IV, and V were used. The degree of interstitial collagen present was scored. The amount of type I collagen was increased in transplants from distant donors (mean ischemia time, 154 minutes) compared with those from on-site donors (mean ischemic time, 59 minutes): collagen scores 1.1 and 1.7, respectively (P less than .01). There was a trend toward a positive correlation, not statistically significant, between cyclosporine dose and collagen III deposition (r = .35), collagen IV (r = .38), and collagen V (r = .56). There was a negative correlation between number of rejection episodes and mean cyclosporine dose (r = .41) and amount of collagen III (r = -.42) or collagen IV (r = -.42). No correlations were found between collagen deposition and any other variables studied. These results confirm the mixed nature of the collagen deposited and suggest that some fibrosis is related to cyclosporine administration rather than to the number of prior healed rejection episodes. PMID- 2318486 TI - Collecting duct carcinoma of the kidney. AB - Collecting duct carcinoma is an unusual variant of renal cell carcinoma, whose appearance and behavior are not well established. We identified six cases of collecting duct carcinoma in our files. The clinical, pathologic, and immunohistochemical characteristics of these tumors are reported. The most common symptom was gross hematuria (four cases). Two patients had cervical adenopathy due to metastatic tumor. Four rapidly developed systemic metastases and died within 4 to 24 months. The primary renal tumors were located predominantly in the renal medulla and pelvis and had a partially cystic white-gray appearance. Histologic examination showed prominent tubulopapillary structures, nests of clear cells, and infiltrating tubules in a dense desmoplastic stroma. Atypical hyperplastic changes were found in some of the adjacent collecting ducts. Mucicarminophilic material was present in glandular elements in all six cases. Immunohistochemical studies revealed positivity with antibodies to epithelial membrane antigen, keratins, peanut agglutinin, vimentin, Leu M1 and lysozyme. The location of this tumor in the medulla, its distinctive histologic appearance, mucin positivity, expression of high molecular weight cytokeratins, and peanut agglutinin suggest that this is a distinct clinicopathologic entity which has an aggressive clinical course. PMID- 2318487 TI - Bone marrow involvement in large granular lymphocyte leukemia. PMID- 2318488 TI - Personal goals of recently divorced women. AB - This paper is a report of the synthesis of feminism and science in a study of the personal goals of recently divorced women with children. The divorce records of three counties were used to identify the participants; eight categories described the primary goals identified by 250 women. Independence, followed by employment and education were the most frequently cited categories. Analysis of variance was computed to analyze the relationships among the primary goal categories, the personal characteristics of the women and their feminist attitudes. Age was the only variable related to selection of a primary goal. Older women chose employment and environmental goals more often than they did mental health goals. PMID- 2318489 TI - Perceptions of body image and health status in persons with mitral valve prolapse. AB - Twenty subjects with diagnosed Mitral Valve Prolapse (MVP) were interviewed regarding self-care needs. Transcripts were analyzed for evidence of perceived health state and altered body image. The majority of subjects described experiences indicating that their perceptions of body image and health state were affected by the diagnosis of MVP. Using Smith's (1981) four categories of health perceptions, most subjects were judged to perceive their health state from a combination of clinical, role-performance and adaptive perspectives. PMID- 2318490 TI - On bargains ... PMID- 2318491 TI - Women's informational needs about colposcopy. AB - Questions asked by 36 women during colposcopy, a stressful medical procedure, were examined to determine their specific informational needs about the exam and its results. Of the 226 questions posed, 52 percent were exam related--on the sensations experienced, the nature of the procedure and self-care activities; 34 percent were results related and focused on the meaning of the results, treatment options and treatment procedures; 14 percent of the questions were incidental. The present research documents women's need for information about the medical procedure of colposcopy. The implications for nursing practice are outlined. PMID- 2318492 TI - Seeking safe passage: utilizing health care during pregnancy. AB - This grounded theory study was conducted to explore how women utilize health care during pregnancy. The 27 women who were interviewed had sought prenatal care early, late or not at all. Transcriptions from the interviews were subjected to constant comparative analysis. The major concern of the women was seeking safe passage through pregnancy and childbirth. Processes used to achieve safe passage were searching for care, consulting, transferring, waiting, contingency planning and self-care. Discussed in this paper is the role that choice plays in utilizing care and transferring some elements of prenatal care to women to manage themselves. PMID- 2318493 TI - Literary works as a mode of knowing. AB - The phenomena of nursing are deeply rooted in the human condition. Knowledge of human responses is developed in the arts as well as the sciences. Literary works often reveal much about human responses that are a foundation for providing compassionate care for patients. PMID- 2318494 TI - How to write a research grant proposal. AB - Good writing will not of itself produce a good research grant proposal. Nevertheless, a well-organized, well-written proposal can help you get funded, so it's worth some effort. This article provides guidelines for writing all the standard parts of a proposal. PMID- 2318495 TI - Clinical support for eliminating the nursing diagnosis of knowledge deficit. PMID- 2318496 TI - Rethinking moral reasoning theory. PMID- 2318497 TI - Phylogeny of the major histocompatibility complex. PMID- 2318499 TI - The nurse practitioner: an expanded role within nursing. PMID- 2318498 TI - The law and nursing. PMID- 2318500 TI - Up close. Interview by Julie Samson. PMID- 2318501 TI - Controlling your use of credit. PMID- 2318502 TI - The impact of clinical information systems on the future of nursing. PMID- 2318503 TI - Grieving. PMID- 2318504 TI - Hospice nursing: a unique career opportunity. PMID- 2318505 TI - The importance of being there. PMID- 2318506 TI - Comparing the grief reactions of a rehabilitation patient and a psychiatric patient. PMID- 2318507 TI - Stillbirth: what the nurse should and should not do. PMID- 2318508 TI - Reach out and touch. PMID- 2318509 TI - Images of caring. Him. PMID- 2318510 TI - Immune response to Acanthocheilonema viteae infection in multimammate rats (Mastomys natalensis). AB - The multimammate rat Mastomys natalensis, when infected with the filarial parasite Acanthocheilonema viteae, develops amicrofilaraemia. Worm recovery and the duration and intensity of microfilaraemia were analysed and related to the humoral and cellular immune responses of the host by using an antibody-dependent cell-mediated cytotoxicity (ADCC) assay towards microfilariae (Mf). Mf were detected in the peripheral blood at 7 weeks post-infection (p.i.), reaching maximum levels by 20 weeks p.i., and then gradually decreasing to undetectable levels during the next 36 weeks. The cytotoxic antibodies appeared around 15-18 weeks p.i., and the serum at 36 weeks p.i. induced 70% cytotoxicity to the Mf in vitro in the presence of host cells. The IgM fraction of the immune serum from amicrofilaraemic Mastomys promoted ADCC to Mf both in vitro and in vivo. Macrophages were more potent in inducing cytotoxic effect than eosinophils and neutrophils. Platelets were ineffective in killing the Mf in the presence of immune serum. IgM antibody cleared the circulating Mf from the blood when given passively to infected Mastomys. The average recovery of adult worms was about 20% of the inoculated larvae. No live females could be recovered 56 weeks p.i. Thus protective immune responses built up over an extended period of time are elicited against the Mf and perhaps even to adults in Mastomys infected with A. viteae. PMID- 2318511 TI - Improvement in sensitivity of enzyme-linked immunosorbent assay for tumour necrosis factor. AB - Various protocols were used in the development of enzyme-linked immunosorbent assays (ELISA) to improve the sensitivity and range of detection of human tumour necrosis factor-alpha (TNF-alpha). ELISA can provide a specific, sensitive and rapid method for detection of TNF-alpha in patient's sera, and it is important that the assay used should be sufficiently sensitive to detect low levels of TNF alpha. The double sandwich ELISA proved to be the most sensitive, detecting less than 0.080 ng/mL TNF. Of eight different protocols, one assay using a purified monoclonal antibody to human TNF-alpha and rabbit polyclonal anti-TNF-alpha antibody had the greatest sensitivity and range of detection. The study illustrates methods for the development of sensitive immunoassays which may have applications in many assay systems. PMID- 2318512 TI - Prevention of adjuvant-induced cachexia in rats by cyclosporin A. AB - The changes in food intake and biochemistry following Freund's adjuvant (AJ) induced inflammation in rats were investigated. Injection of AJ into rats resulted in a transient anorexia but a sustained decrease in body weight. Within 14 days, body weight decreased by 12% (P less than 0.05) and adipose tissue (retroperitoneal fat pads) decreased by more than 50%. Biochemical changes seen in association with the AJ-induced wasting included decreased plasma concentrations of triglyceride and cholesterol. Injection of cyclosporin-A (CS) (20 mg/kg) with the AJ decreased the anorexia, prevented the sustained loss of body weight and adipose tissue and reversed the effects on plasma triglyceride and cholesterol concentrations. Insulin concentrations were not significantly affected by the AJ or AJ/CS treatments. Peritoneal macrophages from AJ-treated rats produced 3-fold more tumour necrosis factor-alpha (cachectin) than control rats. This effect was not observed in rats treated with AJ plus CS. The results are consistent with CS preventing the release of cytokines which have anorectic and catabolic actions (IL-1, TNF), although there is also the possibility that CS has effects involving endocrine mechanisms. PMID- 2318514 TI - HLA-DRB nucleotide sequences, 1990. PMID- 2318513 TI - Nomenclature for factors of the HLA system, 1989. The WHO Nomenclature Committee. PMID- 2318515 TI - Membrane-bound and water-soluble nonclassical class I MHC antigens on rat placenta. AB - We have used mouse monoclonal antibodies to different determinants on rat class I major histocompatibility complex (MHC) antigens in order to identify water soluble and membrane-bound nonclassical (i. e., non-RT1.A) class I MHC antigens on the spongiotrophoblast and labyrinthine trophoblast of rat placenta. Initial immunohistological studies with monoclonal antibodies reacting with a determinant restricted to classical (RT1.A) rat class I antigens confirmed the presence of these antigens on spongiothrophoblast, but not on labyrinthine trophoblast. Staining with another monoclonal antibody, which reacts with both classical and at least some nonclassical rat class I antigens, gave strong staining of both the labyrinthine and spongiotrophoblast. To distinguish membrane-bound from water soluble class I molecules, quantitative absorption analyses were carried out using both placental cell membranes and ultracentrifuged aqueous extracts of placenta. The aqueous placental extract had no absorptive capacity for the RT1.A specific antibodies, but it had very strong absorptive capacity for the more broadly reactive antibody. This strongly suggests the presence of large quantities of a soluble nonclassical class I MHC antigen in rat placenta. The placental cell membranes had four to fivefold greater absorptive capacity for the broadly reactive antibody when compared to the antibodies to classical class I antigens, a result that was consistent with the presence of membrane-bound nonclassical class I antigens on rat placenta. The membrane-bound nonclassical class I antigen was purified from detergent extracts of DA rat placental membranes using monoclonal antibody affinity and lentil lectin affinity chromatography. The putative nonclassical class I antigen had a heavy chain of Mr 43,000, which is 2000 smaller than the classical (RT1.A) class I antigen. N terminal amino acid sequence analysis demonstrated that the nonclassical placental antigen differed at three amino acid residues from the classical RT1.A class I molecule and also from the Q10-like class I molecule of the DA strain. It differed also from the pAR 1.5 cDNA sequence, the only full-length rat class I DNA sequence available so far. PMID- 2318516 TI - The transport of class I major histocompatibility complex antigens is determined by sequences in the alpha 1 and alpha 2 protein domains. AB - The transport of human-mouse hybrid class I histocompatibility antigens has been studied in a mutant human cell line, 174 X CEM.T2 (T2). T2, a somatic cell hybrid of human B- and T-lymphoblastoid cell lines (B-LCL and T-LCL, respectively), synthesized HLA-A2 and HLA-B5 glycoproteins, but expresses only low levels of A2 and undetectable levels of B5 at the cell surface. We have previously shown that the products of human class I genes introduced into T2 by transfection behave like the endogenous HLA-B5 glycoproteins, while the products of mouse class I alleles similarly introduced are transported normally to the cell surface. We have now determined that the surface expression of class I glycoproteins in T2 depends on the origin of the alpha 1 and alpha 2 domains. Human (HLA-B7) and mouse (H-2Dp) hybrid class I genes, encoding the leader, alpha 1, and alpha 2 sequences of one species fused to the alpha 3, transmembrane, and cytoplasmic domains of the other, were transfected into T2. Normal surface expression of the hybrid class I molecule was observed in T2 only when the leader, alpha 1, and alpha 2-encoding exons were derived from the mouse gene. The reciprocal construct, encoding human leader, alpha 1, and alpha 2 domains fused to the mouse alpha 3, transmembrane, and cytoplasmic regions, resulted in biosynthesis of a hybrid glycoprotein which was not transported to the cell surface. The products of both constructs were expressed normally in control cells. The effects of glycosylation on class I antigen transport were also studied using mutant class I constructs with altered glycosylation sites. Two mutant B7 genes encoding either an extra glycosylation site at position 176 or no glycosylation sites were transfected into T2. These mutant products were expressed at the cell surface in control cells, but were synthesized and not surface-expressed in T2. These data demonstrate that the HLA/H-2 transport dichotomy in T2 is a function of the origin of the alpha 1 and/or alpha 2 domains of the class I glycoprotein, and is not a reflection of glycosylation differences between the human and mouse molecules. PMID- 2318518 TI - Treatment of hypertension in the elderly: II. Cognitive and behavioral function. Results of a Department of Veterans Affairs Cooperative Study. AB - This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients. PMID- 2318517 TI - Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study. AB - We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90-114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25-50 mg) or high (50 100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure less than 90 and less than or equal to 5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/l occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a double-blind study to receive hydralazine, methyldopa, metoprolol, or reserpine in addition to hydrochlorothiazide; 79.2% responded to the addition of the second drug and 87.3% of these completed a 6-month maintenance phase. Overall, there were no significant efficacy differences among the step 2 regimens. We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose, and the addition of a second drug was effective and generally well tolerated in elderly patients. PMID- 2318520 TI - Platelet phospholipase C activity in salt-dependent hypertension. AB - In spontaneously hypertensive rats (SHR), enhanced responsiveness of phospholipase C has been reported in various cells and tissues. In SHR and in some patients with essential hypertension particularly, the increased phospholipase C responsiveness of platelets has been described as involved in the hyperreactivity to thrombin. To determine the relation between such an enzymic abnormality and hypertension, the platelet phospholipase C activity was investigated in various models of experimental hypertension (i.e., in the Dahl salt-resistant and salt-sensitive strains inbred by John Rapp at Toledo, Ohio, SR/Jr and SS/Jr, respectively) fed either on a low or a high NaCl-containing diet, and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phosphorus-32-prelabeled platelets, phospholipase C was determined by measurement of the thrombin-induced [32P]phosphatidic acid formation; the labeling of the P47 protein with 32P was also measured. In parallel experiments, the platelet reactivity was assessed by measurement of the thrombin-induced serotonin release. Under thrombin (0.05-0.5 units/ml) stimulation, phospholipase C activity, [32P]P47 labeling, and serotonin release were significantly increased in SS/Jr rats fed a high NaCl diet compared with SS/Jr rats fed a low NaCl diet. NaCl-rich diet did not modify phospholipase C in SR/Jr rats. Platelet reactivity and phospholipase C responsiveness were also normal in DOCA-salt hypertensive rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318519 TI - Time course of enhanced adrenal responsiveness to angiotensin on a low salt diet. AB - To assess the rate of activation of the renin-angiotensin-aldosterone axis and enhancement of adrenal responsiveness to angiotensin II (Ang II) with restriction of sodium intake, 16 healthy male subjects were placed initially on a 200 meq daily sodium intake; adrenal responsiveness to Ang II was assessed, and then daily sodium intake was reduced abruptly to 10 meq. Adrenal responses to Ang II were assessed again during the non-steady state interval 24 and 48 hours later, and after balance was achieved in 5-7 days. Renin-angiotensin system activation was evident within 24 hours after sodium intake was restricted. The increase in basal plasma aldosterone concentration and enhancement of the adrenal response to Ang II, on the other hand, tended to lag. Within 24 hours of restricting sodium intake, despite a significant increase in both plasma renin activity (1.0 +/- 0.2 vs. 2.4 +/- 0.7 ng/ml/hr, p less than 0.01) and Ang II concentration (22.0 +/- 1.9 vs. 29.5 +/- 1.3 pg/ml, p less than 0.05), there was no increase in basal plasma aldosterone concentration (10.4 +/- 1.3 vs. 11.7 +/- 1.2 ng/dl). At 48 hours, despite little further change in plasma renin activity or plasma Ang II concentration, there was a sharp increase in basal plasma aldosterone concentration (22.5 +/- 3.6 ng/dl, p less than 0.01). The adrenal response to Ang II was increased significantly at 24 hours, evident at only a 10 ng/kg/min dose, but showed progressive further enhancement with time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318521 TI - Microvascular alterations in adult conscious spontaneously hypertensive rats. AB - The dorsal skin flap technique was used to study skeletal muscle microcirculation in conscious 10-12-week-old spontaneously hypertensive rats and normotensive Wistar-Kyoto control rats. Videorecordings were made for off-line analysis of consecutive segments of the vascular bed. Resting diameters were significantly smaller in spontaneously hypertensive rats than in Wistar-Kyoto rats at the first order (-28%) and second-order arteriolar (-21%) levels. Precapillary third-order and fourth-order arterioles of spontaneously hypertensive rats had normal diameters, whereas postcapillary small venule diameters were slightly larger in spontaneously hypertensive rats. Thirty percent and 41% of the spontaneously hypertensive rat and Wistar-Kyoto rat third-order arteriolar vessels and 63 and 45% of the fourth-order arteriolar vessels exhibited vasomotion. Vasomotion amplitude, but not frequency, was significantly higher in spontaneously hypertensive rats than in Wistar-Kyoto rats. It is concluded that, in the established phase of spontaneous hypertension in the rat, a decreased diameter of large arterioles is the major mechanism underlying the increased vascular resistance in cutaneous skeletal muscle. PMID- 2318522 TI - Effect of dietary salt on the skeletal muscle microvasculature in Dahl rats. AB - The purpose of this study was to identify microvascular alterations that could contribute to increased peripheral vascular resistance in the Dahl salt-sensitive rat with salt-induced hypertension. Intravital microscopy was used to study the spinotrapezius muscle arteriolar network in anesthetized salt-sensitive rats fed either a high salt (7% sodium chloride) or low-normal salt (0.45% sodium chloride) diet for 4 weeks. Age-matched Dahl salt-resistant rats on high and low normal salt diets served as controls. The high salt diet had no effect on arterial pressure in salt-resistant rats but increased arterial pressure in salt sensitive rats. Mean resting diameter of arcade arterioles in salt-sensitive rats on high salt diet was reduced by 25% compared with salt-sensitive rats on low salt or salt-resistant rats on either diet. After abolition of vascular tone with 10(-3) M adenosine, arcade diameters were comparable in all groups. No difference among groups was found in either resting or passive diameter of the more distal transverse arterioles. Measurement of vessel lengths and numbers in cleared muscle specimens revealed no differences among groups in the anatomic density of either arcade or transverse arterioles. These data suggest that a reduction in the resting diameter of arcade, but not transverse, arterioles may increase spinotrapezius muscle vascular resistance in hypertensive salt-sensitive rats. The similarity in vascular densities among groups indicates that structural rarefaction of arterioles does not contribute to any increase in spinotrapezius muscle resistance at this stage of salt-induced hypertension. PMID- 2318523 TI - New directions for microvascular research in hypertension. PMID- 2318524 TI - Hypertension in rats induced by renal grafts from renovascular hypertensive donors. AB - Renal transplantations were performed, using microsurgical techniques, with adult male two-kidney, one clip hypertensive rats (n = 9) and sham-operated normotensive Wistar-Kyoto rats (n = 8) as kidney donors and with F1 hybrids, bred from Wistar-Kyoto and stroke-prone spontaneously hypertensive rat parents, as recipients. Systolic blood pressure before surgery was 200 +/- 2.7 mm Hg in hypertensive and 115 +/- 1.7 mm Hg in normotensive donors and 144 +/- 7.1 and 138 +/- 3.5 mm Hg in the two groups of recipients. Renal hypertension in donors was maintained for 14 weeks before surgery was performed and the nonischemic kidneys were transplanted. Bilaterally nephrectomized recipients of renal grafts from hypertensive donors developed sustained hypertension (185 +/- 3.9 mm Hg). In contrast, in recipients of renal grafts from normotensive donors, blood pressure decreased significantly to the level of the donors (111 +/- 3.7 mm Hg). Posttransplantation hypertension in recipients of renal grafts from hypertensive donors was associated with intrarenal vascular hypertrophy, smaller kidneys, a decreased glomerular filtration rate, an increased plasma urea concentration, and polydipsia as compared with normotensive transplanted controls. Renal pyelograms revealed no gross anatomic alterations of transplanted kidneys. Our data indicate that secondary damage to the renal grafts caused by high perfusion pressure before transplantation can induce hypertension in recipients of these kidneys. Furthermore, our data suggest that renal mechanisms may be necessary to maintain borderline hypertension in F1 hybrids. PMID- 2318525 TI - Effects of interstrain renal transplantation on NaCl-induced hypertension in Dahl rats. AB - Previous studies using renal transplantation suggested that the genotype of a homograft kidney plays the primary role in determining chronic arterial pressure levels in Dahl salt-sensitive (DS) and salt-resistant (DR) rats, but this conclusion derived largely from observations during low NaCl diet. Recent studies indicate that extrarenal factors, including the sympathetic nervous system, play a critical role in the development of NaCl-induced hypertension in DS rats. To assess the contribution of extrarenal and renal factors in the development of NaCl-induced hypertension in Dahl rats, we performed renal transplantation in DS and DR rats. Both kidneys of the recipient were removed at the time of transplantation. Four groups of rats (n = 18-23 in each group) were fed a high NaCl (8.0%) diet for 2 weeks after renal transplantation. These included DRR, DRS, DSR, and DSS, where DR or DS indicates the recipient strain and the subscript indicates the homograft strain. Mean arterial pressure was measured from the femoral artery in conscious rats. On a high NaCl diet, mean arterial pressure was significantly lower (p less than 0.05) in DRR (103 +/- 2 mm Hg; mean +/- SEM) compared with DRS (145 +/- 5 mm Hg), DSR (151 +/- 7 mm Hg), and DSS (160 +/- 5 mm Hg). The finding that DR rats with a DS kidney (DRS) developed hypertension during high NaCl diet confirms the concept that the kidney plays an important hypertensinogenic role in the Dahl strain. The fact that DS rats with a DR kidney (DSR) also developed hypertension indicates that extrarenal factors also contribute significantly to NaCl-induced hypertension in DS rats. PMID- 2318526 TI - Cloning and expression of functional fragment C of tetanus toxin. AB - A segment of Clostridium tetani DNA corresponding to fragment C of tetanus toxin was amplified by using the polymerase chain reaction. This fragment was cloned into expression vector pTTQ8, under the control of the tac promoter. Expression of this plasmid in Escherichia coli resulted in the production of a protein consisting of 8 amino acids of the vector fused to the C-terminal 460 amino acids of tetanus toxin. This protein (rFragment C) was recognized by an antipeptide antibody specific for fragment C in an enzyme-linked immunosorbent assay and on immunoblots. rFragment C could be purified significantly in one step by immunoaffinity chromatography. Immunization of mice with rFragment C resulted in the production of antibodies that were able to protect the mice against a challenge with tetanus toxin. rFragment C bound to ganglioside GT1b and to neuronal cells in a manner indistinguishable from that of fragment C obtained by papain cleavage of tetanus toxin. For many applications, rFragment C appears to be a suitable alternative to tetanus toxin or toxin-derived fragment C. PMID- 2318527 TI - Protein and antigenic heterogeneity among isolates of Bacillus piliformis. AB - Protein and antigenic heterogeneity among isolates of Bacillus piliformis, the etiologic agent of Tyzzer's disease, were investigated. The seven isolates utilized in this study were originally isolated from naturally infected animals of different animal species and diverse geographical locations. Isolates were propagated in mammalian cell lines, and bacterial extracts were prepared. Protein and antigenic profiles were compared among isolates, using Coomassie blue-stained polyacrylamide gels and Western blot (immunoblot) analyses, respectively. Results showed differences in protein and antigen banding patterns, indicating diversity among isolates. Western blots probed with serum preabsorbed with a heterologous bacterial extract revealed that numerous antigens have different electrophoretic mobilities among isolates but apparently share common epitopes. Immunodominant cross-reactive antigens may be candidate proteins useful for development of improved serologic diagnostic tests, allowing identification of animals infected with a wide range of B. piliformis isolates. PMID- 2318528 TI - Chlamydia trachomatis-host cell interactions: role of the chlamydial major outer membrane protein as an adhesin. AB - The major outer membrane protein (MOMP) of Chlamydia trachomatis is characterized by four symmetrically spaced variable domains (VDs I to IV) whose sequences vary among serotypes. The surface-exposed portions of these VDs contain contiguous sequences that are both serotyping determinants and in vivo target sites for neutralizing antibodies. Previous studies using surface proteolysis of C. trachomatis B implicated VDs II and IV of the MOMP of this serotype in the attachment of chlamydiae to host cells. In this study, we used monoclonal antibodies (MAbs) specific to antigenic determinants located in VDs II and IV of the MOMP of serotype B to further investigate the role of the MOMP in the attachment of chlamydiae to host cells. MABs specific to serotype- and subspecies specific epitopes located in exposed VDs II and IV, respectively, neutralized chlamydial infectivity for hamster kidney cells by blocking chlamydial attachment. We radioiodinated these MAbs and used them to determine the number and topology of the surface-exposed VDs II and IV epitopes on chlamydial elementary bodies. VDs II and IV each comprised approximately 2.86 x 10(4) negatively charged sites and were in proximity on the chlamydial cell surface. These studies suggest that the MAbs blocked chlamydial attachment by inhibiting electrostatic interactions with host cells. We examined the effects of thermal inactivation on both chlamydial attachment and conformation of the MOMP. Heat inactivated chlamydiae failed to attach to host cells and exhibited a conformational change in an inaccessible invariant hydrophobic nonapeptide sequence located within VD IV of the MOMPs of C. trachomatis serotypes. These findings suggest that in addition to electrostatic interactions, a common hydrophobic component of the MOMP also contributes to the binding of chlamydiae to host cells. Thus, we propose that the MOMP functions as a chlamydial adhesin by promoting nonspecific (electrostatic and hydrophobic) interactions with host cells. Surface-accessible negatively charged VDs appear to be important in electrostatic binding, while the invariant region of VD IV may provide a subsurface hydrophobic depression which further promotes binding of chlamydiae to host cells through hydrophobic interactions. PMID- 2318529 TI - Thermoregulation of protein synthesis in Borrelia burgdorferi. AB - Borrelia burgdorferi, the etiological agent of Lyme disease, infects humans via the bite of a tick. The microbe survives in at least two vastly different environments: an arthropod vector and a warm-blooded host. We examined protein synthesis in B. burgdorferi B31 in response to sudden heat stress, which is similar to that which occurs during the transmission from vector to host. Proteins synthesized after shifts from 28 degrees C to higher temperatures and in pulse-chase experiments were labeled with 3H-labeled amino acids for 4 h and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. The synthesis of four proteins we designated as heat stress proteins (HSPs) was increased by shifts to higher temperatures (HSP-1, 75 kilodaltons [kDa]; HSP-2, 42 kDa; HSP-3, 39 kDa; and HSP-4, 27 kDa); and the amount of one protein we designated as heat-labile protein 1 (29.5 kDa) was decreased at higher temperatures. At 37 to 40 degrees C, the major heat stress protein, HSP-1, represented 14 to 18% of the total cell protein compared with 1 to 2% of the total cell protein at 28 degrees C. HSP-1 was stable during a 4-h chase at either 40 or 28 degrees C. Demonstration of similar HSPs in low-passage, pathogenic strains of B. burgdorferi suggests that the heat stress response may be common among B. burgdorferi strains and may play a role in Lyme disease. PMID- 2318530 TI - Isolation, characterization, and inhibition kinetics of enolase from Streptococcus rattus FA-1. AB - One aspect in a broad spectrum of possible mechanisms of cariostatic reactions of fluoride is its interaction with the metabolism of oral bacteria. Information on the mechanisms and kinetics of fluoride inhibition of essential enzymes of the glycolytic pathway of the relevant bacteria is lacking. In this work, the isolation and purification of enolase from Streptococcus rattus and its characterization are described. The enzyme has been isolated in a monomeric (22 kilodaltons) and dimeric (49 kilodaltons) form. The Km for 2-phosphoglycerate is 4.35 mM. Fluoride inhibition kinetics have competitive character, while phosphate in concentrations above 2 mM and in the presence of 0.5 mM fluoride alters the inhibition kinetics from competitive to noncompetitive. Without fluoride, 2 mM phosphate has a slight stimulatory effect on the enzyme. Monofluorophosphate has a noncompetitive inhibiting effect on the enzyme. This finding suggests that the effect of phosphate may be due to an additional binding of fluoride to the enolase, resulting in a conformational change of the enzyme. PMID- 2318531 TI - Phagocyte function in juvenile periodontitis. AB - We studied the chemotaxis of peripheral blood polymorphonuclear leukocytes (PMNs) and monocytes and the production of tumor necrosis factor alpha by monocytes of patients with juvenile periodontitis (JP). As a group, the patients' PMNs showed significantly increased chemotaxis determined by counting the number of migrating cells within a 3-microns-pore-size filter. Determined as distance of migration within the filter, as chemotactic increment based on checkerboard analysis, as leukotactic index calculated on the basis of distance of migration and cell count at different depths within a 3-microns-pore-size filter, as distance of migration under agarose, and as the number of PMNs migrating across a 5-microns-pore-size filter, the chemotactic migration rates of PMNs of patients were similar to those of controls. Evaluation of the data on an individual basis suggested that in terms of PMN chemotaxis some patients were hyperresponsive and some were hyporesponsive. Chemotaxis, spontaneous migration, and the rates of lipopolysaccharide-induced tumor necrosis factor alpha production by JP monocytes were similar to those of control cells. Our results give credence to the view that there are minor aberrations in the functions of JP phagocytes, but the extent to which these aberrations are relevant to accumulation of PMNs at sites of infection and inflammation in vivo and possibly contribute to the pathogenesis of JP remains unclear. PMID- 2318532 TI - Cyclic rickettsemia during persistent Anaplasma marginale infection of cattle. AB - Submicroscopic levels of Anaplasma marginale rickettsemia in persistently infected cattle were determined by using nucleic acid hybridization. Within individuals, the rickettsemia levels steadily increased from less than 10(4) infected erythrocytes per ml to a peak of more than 10(6) infected erythrocytes per ml and then rapidly declined. This logarithmic variation parallels the variation of the rickettsemia level seen in acute infection and suggests that cyclic emergence of antigenic variants is a mechanism of rickettsial persistence. PMID- 2318533 TI - Borrelia burgdorferi contains repeated DNA sequences that are species specific and plasmid associated. AB - Borrelia burgdorferi, the causative agent of Lyme borreliosis, contains linear and supercoiled circular (SC) plasmids. Because SC plasmids are present in multiple copies, these plasmids were examined for species-specific sequences that could serve as high-copy-number target DNAs for a diagnostic probe. Three EcoRI fragments (4.3, 4.2, and 3.5 kilobase pairs [kb]) that hybridized with multiple DNA fragments from B. burgdorferi were identified and cloned from a SC plasmid enriched fraction. The 4.2- and 3.5-kb fragments were similar in that they hybridized with each other and with similar-sized EcoRI fragments from two unrelated strains of B. burgdorferi. The 4.3-kb fragment did not hybridize with the other two cloned sequences. Both types of sequences hybridized with most of the SC plasmids in seven B. burgdorferi isolates, whereas only a single 49-kb linear plasmid, found in two of the seven strains tested, hybridized with the cloned sequences. None of the cloned sequences hybridized with chromosomal DNA from B. burgdorferi or with total DNA or SC plasmids from Borrelia hermsii, B. turicatae, B. coriaceae, B. parkeri, or B. anserina. These data indicate that the repeated DNA sequences described in this study appear to be plasmid associated and specific to B. burgdorferi. Heteroduplexes formed from the 4.2- and 3.5-kb fragments showed that hybridizing regions in each fragment comprise a 1.8-kb conserved region that is adjacent to a 1.5-kb region that exhibits greater sequence variability. The sequence divergence seen in the variable region is likely the result of genetic drift and may mean that these regions represent closely related genes that encode functionally similar but antigenically distinct proteins. PMID- 2318534 TI - Multiple mechanisms in serum factor-induced resistance of Haemophilus influenzae type b to antibody. AB - Incubation of Haemophilus influenzae type b at less than or equal to 10(7) CFU/ml with serum ultrafiltrate induces a phenotypic conversion in which complement mediated bactericidal activity by somatic antibodies decreases while killing by capsular antibody is unchanged. Conversion had been shown to occur in a capsule deficient (b-) mutant of strain Eag (thus appearing independent of capsulation), to include an increase in lipopolysaccharide content, and to be inhibited by chloramphenicol or puromycin. In the present study, in several strains not previously examined, conversion was not inhibited by the drugs and the corresponding b- mutants did not convert. Incubation in ultrafiltrate was also found to increase capsulation, as detected by radioassay, only 1.6-fold in Eag but 4.5-fold in DL26, the strain with the largest increase in resistance; moreover, complement-mediated opsonization by capsular antibody was greatly decreased. Thus, multiple mechanisms, capsule dependent as well as independent, appear to contribute to the serum factor-induced resistance of H. influenzae type b to antibody. PMID- 2318535 TI - Nucleotide sequence of the leukotoxin gene from Actinobacillus actinomycetemcomitans: homology to the alpha-hemolysin/leukotoxin gene family. AB - The leukotoxin produced by Actinobacillus actinomycetemcomitans has been implicated in the etiology of localized juvenile periodontitis. To initiate a genetic analysis into the role of this protein in disease, we have cloned its gene, lktA. We now present the complete nucleotide sequence of the lktA gene from A. actinomycetemcomitans. When the deduced amino acid sequence of the leukotoxin protein was compared with those of other proteins, it was found to be homologous to the leukotoxin from Pasteurella haemolytica and to the alpha-hemolysins from Escherichia coli and Actinobacillus pleuropneumoniae. Each alignment showed at least 42% identity. As in the other organisms, the lktA gene of A. actinomycetemcomitans was linked to another gene, lktC, which is thought to be involved in the activation of the leukotoxin. The predicted LktC protein was related to the leukotoxin/hemolysin C proteins from the other bacteria, since they shared a minimum of 49% amino acid identity. Surprisingly, although actinobacillus species are more closely related to pasteurellae than to members of the family Enterobacteriaciae, LktA and LktC from A. actinomycetemcomitans shared significantly greater sequence identity with the E. coli alpha-hemolysin proteins than with the P. haemolytica leukotoxin proteins. Despite the overall homology to the other leukotoxin/hemolysin proteins, the LktA protein from A. actinomycetemcomitans has several unique properties. Most strikingly, it is a very basic protein with a calculated pI of 9.7; the other toxins have estimated pIs around 6.2. The unusual features of the A. actinomycetemcomitans protein are discussed in light of the different species and target-cell specificities of the hemolysins and the leukotoxins. PMID- 2318536 TI - Differences in susceptibilities of the lymphogranuloma venereum and trachoma biovars of Chlamydia trachomatis to neutralization by immune sera. AB - Sera from seven patients from whom a C. trachomatis serovar L2 strain was isolated were tested in vitro for their ability to neutralize the infectivity of this organism. In one patient an inguinal lymph node was culture positive, whereas the remaining six patients had positive rectal biopsies. Sera from four of the patients, including the patient with the lymph node isolate, failed to neutralize serovar L2(434). In addition, the homologous strain recovered from the inguinal lymph node was available and was resistant to neutralization by the homologous sera. However, the same sera effectively neutralized a trachoma serovar, E(Bour). All four sera had inclusion immunofluorescent-antibody titers to C. trachomatis serovar L2 of 2,048 to 16,384 and microimmunofluorescent antibody titers to the lymphogranuloma venereum biovar were equal or higher in all cases than to the 12 serovars of the trachoma biovar. The three remaining sera, while neutralizing the infectivity of the L2 strains tested, neutralized serovar E to a greater extent. These sera had the same inclusion immunofluorescent antibody titers as the sera that failed to neutralize serovar L2. To see whether this difference in the sensitivity of the biovars toward neutralization could be characterized, sera were obtained from mice immunized with different doses of both serovars L2 and E. Sera obtained from mice immunized with serovar E were able to effectively neutralize the homologous strain. In contrast, neutralization of the immunizing strain, L2(UCI-20), was not seen with sera obtained on days 7, 14, and 21 after immunization from animals receiving 8 x 10(5) and 8 x 10(4) inclusion-forming units of L2(UCI-20); however, these same sera neutralized serovar E. However, with a higher immunizing dose of L2 (10(7) IFUs), both E and L2 were neutralized with sera obtained 7 and 14 days after immunization. Therefore, the relative resistance to neutralization by serovar L2 compared with that of serovar E in the mouse model was inoculum dependent. PMID- 2318537 TI - Expression of the cloned gene for enterotoxin STb of Escherichia coli. AB - This study involved the construction of hybrid plasmids to produce heat-stable enterotoxin type II of Escherichia coli (STb). The translation of the open reading frame for the STb gene estA was demonstrated in several ways. Studies using in vivo labeling with [35S]cysteine demonstrated a radiolabeled protein band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the expected molecular weight of 5,000 for toxin STb. Insertion of translational or transcriptional termination signals into the BglII site of the estA gene blocked the expression of estA. The estA gene was cloned into high-expression vector pKC30 downstream from the strong pL promoter. Northern (RNA) blotting assays revealed a 10- to 20-fold increase in mRNA produced by strain C600F(pKC30STb) over other STb-producing strains, compared with little or no increase in enterotoxin activity demonstrated by bioassay. The estA gene, with its own promoter and Shine-Delgarno region and a portion of the sequence for the signal peptide deleted, was also inserted under the control of the tac promoter. Even after induction of the tac promoter by addition of isopropyl-beta-D thiogalactopyranoside, no biologic enterotoxin activity could be identified. Neutralizing antibodies to STb were produced in rabbits by using either a purified OmpF-STb-beta-galactosidase fusion protein or a 19-amino-acid synthetic STb peptide coupled to keyhole limpet hemocyanin. PMID- 2318539 TI - Purification and N-terminal analysis of urease from Helicobacter pylori. AB - Urease of Helicobacter pylori (formerly Campylobacter pylori) is believed to represent a critical virulence determinant for this species. Ammonia generated by hydrolysis of urea may protect the acid-sensitive bacterium as it colonizes human gastric mucosa. An H. pylori strain, cultured from a gastric biopsy of a patient with complaints of abdominal pain and a history of peptic ulcer disease, was isolated on selective medium and cultured in Mueller-Hinton broth supplemented with 4% fetal calf serum. Whole cells were ruptured by French pressure cell lysis, and soluble protein was chromatographed on DEAE-Sepharose, phenyl Sepharose, Mono-Q, and Superose 6 resins. Purified urease represented 6% of the soluble protein of crude extract, was estimated to have a native molecular size of 550 kilodaltons (kDa), and was composed of two distinct subunits of apparent molecular sizes of 66 and 29.5 kDa. On the basis of subunit size, a 1:1 subunit ratio as measured by scanning densitometry of Coomassie blue-stained sodium dodecyl sulfate-polyacrylamide gels, and estimated native molecular size, the data are consistent with a stoichiometry of (29.5 kDa-66 kDa)6 for the structure of the native enzyme. Km for urea was estimated at 0.2 mM. By N-terminal analysis, the 29.5-kDa subunit of H. pylori urease was found to share significant amino acid sequence similarity with the smallest of three subunits of the Proteus mirabilis and Morganella morganii ureases, as well as to the amino terminus of the unique jack bean subunit. The 66-kDa subunit also shared up to 80% similarity with the largest of three subunits of P. mirabilis, M. morganii, and Klebsiella aerogenes ureases and to internal sequences (amino acids 271 to 285) of the jack bean urease subunit. Thus, the amino acid sequence is conserved among ureases with one, two, and three distinct subunits, suggesting a common ancestral urease gene. Also, urease subunits of M. morganii and jack bean were specifically recognized by antisera raised against the 66-kDa subunit of H. pylori urease, demonstrating that at least some antigenic determinants were conserved among ureases from different species. PMID- 2318540 TI - Career identification and women's attitudes toward retirement. AB - This study seeks to heighten understanding of the retirement process as experienced by women through an examination of working women's attitudes toward retirement. The subjects for this study were 201 female teachers employed in the public school system in a central Oklahoma district. The survey instrument used was a questionnaire consisting of sociodemographic and work-related variables. The findings indicate that overall, females with stronger work identities have significantly more negative attitudes toward retirement than those with weaker work identities; this difference remains significant when controls are introduced for years of teaching experience, expected age of retirement, and attitude toward work. The implications of these findings are discussed. PMID- 2318538 TI - Immunogenic integral membrane proteins of Borrelia burgdorferi are lipoproteins. AB - The pathogenic spirochete Borrelia burgdorferi contains a set of integral membrane proteins which were selectively extracted into the detergent phase upon solubilization of intact B. burgdorferi with the nonionic detergent Triton X-114. Virtually all of these hydrophobic proteins were recognized by antibodies in pooled sera from patients with chronic Lyme arthritis, demonstrating that proteins partitioning into the detergent phase of Triton X-114 encompass the major B. burgdorferi immunogens. Furthermore, most of these immunogenic proteins, including the previously characterized OspA and OspB membrane antigens, could be biosynthetically labeled when B. burgdorferi was incubated in vitro with [3H]palmitate. The OspA and OspB antigens were radioimmunoprecipitated from [3H]palmitate-labeled detergent-phase proteins with monoclonal antibodies, and [3H]palmitate was recovered unaltered from these proteins after sequential alkaline and acid hydrolyses. The combined results provide formal confirmation that the major B. burgdorferi immunogens extracted by Triton X-114 are lipoproteins. The demonstration that B. burgdorferi integral membrane antigens are lipoproteins may explain the basis of their immunogenicity and may help to improve our understanding of the surface topology of B. burgdorferi. PMID- 2318541 TI - A measure of the trust beliefs of elderly individuals. AB - Rotter's trust scale was modified for use as a measure of trust beliefs of elderly individuals. Analyses of 140 elderly individuals' responses on the scale yielded support for its internal consistency, reliability and validity. As evidence for the latter, the scale was correlated with peer sociometric ratings of trusting. Factor analyses revealed that the trust scale was composed of four factors: 1) dependability of social-legal organizations; 2) fear of being cheated; 3) dependability of specific social groups to fulfill their promises; and 4) adherence to trustworthy ideals within society. A complex relationship was found between trust and income; income correlated positively with the total score and both the first and second trust factors, but negatively correlated with the third factor. This was attributed to the tendency of elderly individuals with low income to place their trust in specific groups rather than social-legal organizations, and to their fear of crime. A curvilinear shift with age was found in the first trust factor and was attributed to post-retirement experiences in middle-old age and a form of generativity in very old age. PMID- 2318542 TI - Predicting exercise in late midlife from young adult personality characteristics. AB - This study explored the relationship between personality and exercise over the life span by using young adult personality characteristics to predict current exercise behavior in late middle-aged male graduates from the Harvard University classes of 1942 to 1944. After controlling for prior exercise behavior, body build, and fitness in young adulthood, we found that personality variables improved classification accuracy in discriminant analysis, and especially improved identification of frequent exercisers. Personality variables positively associated with frequent exercise include affective vitality, integration, lack of anxiety, and lack of shyness. Results are interpreted as supporting a psychobiological account of exercise behavior. Caution is suggested in generalizing the results to other populations, such as less privileged socio economic classes or females. PMID- 2318543 TI - Narcissism and loneliness. AB - The research described here centers on how a narcissistic intrusion during early childhood may develop into narcissistic difficulties which manifest themselves, later in life, in feelings of loneliness. The results from a study of elderly women in Stockholm, Sweden, indicated that loneliness in old age is greater among an intruded group in comparison to those whose parental influence was not intrusive. The feelings of loneliness are even more severe if the mother was a housewife. There was also a relationship between social position and loneliness, but only for those women whose family orientation was not intrusive and whose mothers were housewives. The results encourage further study of the etiological contributions of parental influence during childhood on later experience of loneliness. PMID- 2318544 TI - The age of saints and the saintliness of age. AB - The image of the saint as an old person is a familiar one. Does this mental association have any basis in fact? This article reports a study examining the age of saints, and includes a discussion of the saint as a possible model for the old person. The sample of 487 saints (118 females, 369 males) was drawn from reference sources to meet the criteria of a) actual historical person, and b) established dates (years) of birth and death. Those who died as martyrs were analyzed separately. Martyrdom was twice as common among the males. Almost all female martyrs died young; males were more likely to be put to death in their forties. Saints whose lives were not brought to an abrupt end by martyrdom were studied more extensively. Male saints, combining all historical periods, had a mean longevity of 69.9 years: literally the proverbial "three score and ten!" Female saints had a mean longevity of 58.1. A series of quasicomparisons suggests that saints, especially the males, have had a longevity advantage throughout most of history. However, a time trend was noted among the males: the number of very old saints has diminished markedly in recent times, and centenarians, in particular, have been absent for more than seven hundred years. The data suggest that interactions exist between gender and historical period. Four alternative hypotheses about the possible age-saint relationship are examined in light of the present findings, and the saint is explored as a possible model for coping with the burdens and trials of old age, contrasted with current age-based health rationing concepts. PMID- 2318545 TI - Update on the statistical analysis of bioequivalence studies. AB - Statistical methods to assess bioequivalence of a test and a reference formulation are reviewed with emphasis on the distribution of bioequivalence characteristics and the consumer risk of erroneously accepting bioequivalence. Among the procedures not exceeding a nominal consumer risk of 5%, the one with an acceptably small producer risk of erroneously rejecting bioequivalence is selected. With the exception of tmax, the following strategy is recommended: a decision in favour of bioequivalence is made if the shortest 90%-confidence interval for the ratio of the expected medians is in the bioequivalence range for the chosen characteristics of rate and extent of absorption. If the assumption of a logarithmic normal distribution is not valid, the analogous nonparametric (distribution-free) 90%-confidence interval, which is also based on the two sample approach for the sequences reference/test and test/reference, is the procedure of choice. The issue of a modification of the bioequivalence range of 80-120% to other values for bioequivalence characteristics other than AUC (e.g. Cmax) is also addressed. Finally, a decision rule for tmax is presented. PMID- 2318546 TI - Pantothenic acid, acute ethanol consumption and sulphadimidine acetylation. AB - The effect of pantothenic acid and acute ethanol loading on the genetically determined N-acetyltransferase activity has been studied using sulphadimidine as a test substance. The administration of 1100 mg pantothenic acid daily (600 mg orally, 500 mg iv) for seven days did not significantly alter sulphadimidine kinetics in the primarily elderly 21 subjects we investigated. Acute ethanol loading (0.73 g/kg pure alcohol at start and 0.11 g/kg pure alcohol hourly for 8 hours afterwards, stock solution: 20% v/v ethanol in fruit juice) did not change sulphadimidine acetylation in 10 healthy male volunteers. It is concluded that despite theoretical assumptions exogenous factors like pantothenic acid and ethanol do not significantly influence the cytosolic N-acetyltransferase activity. Consequently they do not interfere with the acetylator phenotyping procedure. PMID- 2318547 TI - The effect of hemodialysis on omeprazole plasma concentrations in the anuric patient: a case report. AB - Omeprazole, a drug suppressing gastric acidity secretion was given intravenously at a dose of 40 mg/day to an anuric patient. Pharmacokinetics data indicate that without hemodialysis treatment, the dose can be reduced by 40% without any danger of loss of effectiveness. During hemodialysis however, the full dose must be given. Controlled long-term studies will be required to determine the exact dose for continued treatment. PMID- 2318548 TI - Study of the release process of drugs: suppositories of paracetamol. AB - The release process of paracetamol, formulated in suppositories, prepared with four different Suppocire masses (AM, AML, AS2X and AP), having different hydrophilia, supplied by Gattefosse, was investigated. The release study of paracetamol was carried out "in vitro" by means of the Dissotest apparatus (Sotax), built on the base of the flow-through method. The assay conditions were: pH 7.4 and flow rate of 20 ml/min. The release process was evaluated using the following amodelistic parameters: the mean dissolution time (MDT), the variance of dissolution time (VDT), the dissolution efficiency (DE) and the maximum amount dissolved determined experimentally (Qmax). The amodelistic parameters, after their statistical analysis by the Kruskal-Wallis test, followed by the comparison between data pairs by the Mann-Whitney "U" test, proved that there are significant differences (p less than 0.05), with the exception of Qmax, between the four masses tested. This study shows that the masses which have a surfactant in their composition (AS2X and AP) offer a better release of paracetamol than those which have no surfactant (AM and AML). PMID- 2318549 TI - Reduction in blood viscosity by treatment with coenzyme Q10 in patients with ischemic heart disease. AB - The effects of coenzyme Q10 (CoQ10) on blood viscosity were studied in twelve patients (mean age 49 +/- 16 years) with ischemic heart disease. Twenty mg of CoQ10 was orally administered three times daily for two months (total dose 60 mg per day). Blood viscosity was measured with a cone-plate type viscometer at the shear rates of 37.5, 75, 150, and 375 s-1. Yield shear stress was calculated from Casson's plot. Blood viscosity decreased at each shear rate after the administration of CoQ10. Yield shear stress decreased significantly by the treatment with CoQ10. Hematocrit and fibrinogen were also measured, but showed no significant change. These results suggest that CoQ10 decreases the blood viscosity, i.e., improves the rheological properties of blood in ischemic heart disease. PMID- 2318550 TI - Tubular secretion of creatinine and its plasma concentration. PMID- 2318551 TI - Vinpocetine therapy does not change imipramine pharmacokinetics in man. AB - The influence of vinpocetine on imipramine steady-state plasma levels was investigated in 18 healthy volunteers. Twenty-five mg imipramine were given t.i.d. for a total of 21 days, vinpocetine treatment was started on day 11 with 10 mg t.i.d. and continued until the end of the study. The AUC of imipramine plasma levels were obtained using consecutive imipramine plasma level determinations from samples drawn every 2 h from 8:00 a.m. to 8:00 p.m. by trapezoidal rule. AUCs of day 10 without and of day 21 during concomitant vinpocetine treatment were compared, demonstrating the independence of imipramine's bioavailability from concomitant vinpocetine treatment. There were no indications to assume a changed absorption of imipramine due to vinpocetine as would be reflected in Cmax and tmax values. Imipramine metabolization to the still effective metabolite desipramine shows a huge interindividual variability although it remains constant for the individual. The analysis of this parameter in the course of this study does not suggest that it is changed due to vinpocetine treatment. PMID- 2318552 TI - Response to discussion of "Bereavement Groups: Techniques and Themes". PMID- 2318553 TI - Treating persons with ARC and AIDS in group psychotherapy. AB - The authors describe a range of critical issues that are common within homogeneously composed groups for patients suffering from Acquired Immunodeficiency Syndrome (AIDS) and AIDS Related Complex (ARC). They examine the need for these patients to understand their physical symptomatology, to reconsider life's priorities, and to confront their ethical and moral dilemmas. The authors also highlight special effects, unique group atmosphere and process, and the nature of the group contract that is essential for these patients. PMID- 2318554 TI - The craft of bridging. AB - The author offers the concept of bridging to integrate a variety of techniques used by group psychotherapists to strengthen the emotional bonds among group members. After documenting the need for therapeutic bridging, and highlighting its principal aims, the author illustrates a number of methods, including open ended and direct questions, and invitations to group members to elicit more generalized interaction among group participants. In this way, the therapeutic potential of the group can be optimized. PMID- 2318555 TI - Understanding how groups work: a study of homogeneous peer group failures. AB - The study examines thirty-six homogeneous peer support groups that failed to positively benefit most of the participants. Outcomes were assessed pre and one year post using measures of mental health, marital relationships, and motherhood role indices. Four central group process characteristics previously found to be common in successful peer support groups were used as a framework for developing a series of post hoc hypotheses. The groups were found to be low on cohesiveness defined behaviorally, saliency, cognitive structures for reframing common dilemmas, and limited in the range of therapeutic experiences. PMID- 2318556 TI - Patient activity and outcome in group psychotherapy: new findings. AB - The relation of patient verbal activity to pretherapy symptom status and outcome was examined for ninety patients in time-limited group psychotherapy. For each half-hour segment the most verbally active member, or main actor (MA), was identified. Verbal activity was measured by counting the number of times each patient was MA during the course of the group. Outcome was assessed by administering a battery of instruments pre- and posttherapy and by obtaining direct ratings of patient benefit from the patient, therapist, and an independent rater: the number of times MA was found to be significantly correlated with four pretherapy measures, indicating that the most disturbed patients were most active in these groups; the number of times MA was also correlated with patient and therapist benefit ratings, indicating that therapists and patients themselves agreed that those who spoke the most benefited the most. However, partial correlations between number of times MA and other outcome measures did not produce any significant relationships. Thus, it does not appear that patient verbal activity is related to outcome, as measured by objective instruments. PMID- 2318557 TI - Sexual abuse intervention: a support group for parents who have a sexually abused child. AB - A pilot program for parents of sexually abused children is discussed with a focus on intervention at a systems level. The Parent Support group is based on an eclectic approach and the interventions at the therapeutic and educational levels are described. The evolution of the group is addressed based on the group objectives. Each of the thirteen sessions is described to illustrate the various intervention strategies. Suggestions for implementing a similar group are discussed based on the authors' experience utilizing the presented model. PMID- 2318558 TI - Amelioration of transference resistance: substitute therapists in milieu group psychotherapy. AB - Building upon Wolf's (1949) notion of the use of an alternate session in group psychotherapy, this paper suggests that an alternate therapist substituting for an absent regular therapist in milieu group psychotherapy can facilitate similar therapeutic benefits. The mechanism of this process of overcoming transference resistance is seen as twofold: (1) sessions with a substitute therapist allow patients to confront the infantilization often present in a milieu setting and experiment with more autonomous ego functioning. (2) Sessions with a substitute therapist create conditions which are apart from the ongoing process of the therapy group, thereby allowing for a therapeutic splitting process to develop wherein transference feelings about the regular therapist can be expressed to his or her "alter ego." Several case vignettes are presented in order to illustrate the clinical utility of a substitute therapist. PMID- 2318559 TI - Individual psychotherapy as an adjunct to group psychotherapy. AB - This paper describes a form of combined psychotherapy in which the individual sessions are used as an adjunct to group therapy. Each group member is seen regularly in individual sessions to focus primarily on the member's ongoing group work. The individual sessions are scheduled on a rotating basis. Typically, each group member is seen in an individual session once every four weeks. Additional individual sessions are available only when immediate attention is appropriate and necessary. The group is viewed as the primary therapeutic component. A cost effective therapeutic approach that uses both individual and group methods, this modality lends itself well to a clinic and to a private practice setting. PMID- 2318560 TI - Comparative analysis of arterial oxygen saturations during exercise by pulse oximetry, photometric measurements, and calculation procedures. AB - Pulse oximetry allows non-invasive monitoring of arterial oxygen saturation (SO2). To study the validity of pulse oximetry, comparative measurements were performed. During exhaustion limited exercise SO2-values measured by pulse oximetry (SO2puls), calculated SO2-values (algorithms of Kelman, Severinghaus, and Siggaard-Andersen--SO2calc), and as "golden standard" photometric measured SO2-values (SO2meas) were compared. Fourteen triathletes performed a stepwise cycling exercise test in the supine position. SO2calc was determined on the basis of capillary actual blood gas values. SO2puls was measured continuously with a finger probe attached to the second finger. The SO2puls- and SO2calc-values differed from the SO2meas-values (p less than 0.05); however, the differences were of no clinical relevance. Performing linear regression analysis, only SO2puls correlated significantly (r = 0.47, p less than 0.001) with SO2meas. Pulse oximetry is able to replace invasive measurements of arterial oxygen saturation in athletes. It is superior to SO2-calculations and permits reliable, valid and non-invasive continuous monitoring of SO2. PMID- 2318561 TI - Reliability and validity of a continuous incremental treadmill protocol for the determination of lactate threshold, fixed blood lactate concentrations, and VO2max. AB - Fifteen male runners were tested on two occasions to determine the reliability of a continuous incremental level running treadmill protocol (C), with 3-min stages, for lactate threshold (LT) and fixed blood lactate concentration (FBLC) (2.0 mM, 2.5 mM, 4.0 mM) assessment. Test-retest (T-RT) reliability coefficients for velocity at LT, 2.0 mM, 2.5 mM, and 4.0 mM were r = 0.89, 0.91, 0.95, and 0.95, respectively (velocity ranged from 215.3 m/min at LT to 273.6 m/min at 4.0 mM). Mean differences in T-RT velocity values ranged from 0.7 m/min (at LT) to 6.0 m/min (at 2.5 mM; 252.3 m/min vs 258.3 m/min; NS) and the standard errors of measurement were less than +/- 10.0 m/min. Similar results were observed for VO2, with T-RT r values ranging from r = 0.82 (at LT) to r = 0.88 (at 2.0 mM) (VO2 ranged from 47.2 ml/kg.min-1 at LT to 60.9 ml/kg.min-1 at 4.0 mM; VO2 peak = 65.6 ml/kg.min-1). Mean differences in T-RT VO2 values were less than 1.4 ml/kg.min-1 (NS) and the standard errors of measurement were less than +/- 2.95 ml/kg.min-1. Interinvestigator and intrainvestigator reliability coefficients were high and ranged from r = 0.91 to r = 0.99. Validity of C was assessed in an additional 16 male runners who completed C and a criterion discontinuous (D) protocol (using a series of 10-min stages) for LT and FBLC assessment. Results indicated that C and D resulted in similar VO2 and velocity values at LT and FBLC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318562 TI - Reduced training maintains performance in distance runners. AB - This investigation examined endurance runners during a 3-week reduction in training volume and frequency. Ten well-conditioned runners were monitored for 4 weeks while training at their normal weekly training distance (mean +/- SE) (81 +/- 5 km/week, 6 days/week). This period was designated as baseline training (BT). Sixty km/week were run at approximately 75% VO2max, and the remainder (21 km/week) at approximately 95% VO2max in the form of intervals and races. The runners then reduced weekly training volume (RT) by 70% of BT to 24 +/- 2 km/week and frequency by 17% to 5 days/week for 3 weeks. During RT 17 km/week was performed at approximately 75% VO2max and the remainder (7 km/week) at approximately 95% VO2max (intervals and races). The runners were tested weekly and performed 5-km races on a 200-m indoor track during Bt and after 2 and 3 weeks of RT. Maximal heart rate (HR) increased (P less than 0.05) by approximately 4 beats/min at RT week 3, which may have been associated with a decrease in estimated plasma volume (P less than 0.01) of 5.62 +/- 0.43%. Time to exhaustion during the VO2max tests increased (P less than 0.05) by 9.5% at RT week 3. No significant (P greater than 0.05) changes occurred with RT in body weight, % body fat, overall 5 km race times, VO2max, muscular power (vertical leap and Margaria power test), and citrate synthase activity (at 2 weeks of RT). No alterations in venous lactate, energy expenditure, and HR were observed during submaximal running at two speeds (approximately 65% and 85% VO2max) with RT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318563 TI - Aerobic physical training and alterations in pressor response during norepinephrine infusion: a controlled single-subject experiment. AB - To test the influence of aerobic physical training on pressor response to infused norepinephrine, the present study utilized a single subject A-B-A-B withdrawal design consisting of 9-week alternating sedentary and aerobic phases (S1, A1, S2, A2). During each 9-week phase the subject underwent infusions every 3 weeks, consisting of saline, low-dose and high-dose norepinephrine (Low-NE, High-NE). Heart rate and mean arterial blood pressure were monitored continuously; resting platelet and plasma catecholamines were also measured. Infusions were conducted 48 h from the most recent exercise bout to minimize residual effects of acute exercise. Fitness level was confirmed by VO2max during graded exercise testing at the conclusion of each 9-week phase. Blood pressure during saline did not differ between aerobic and sedentary phases. However, in all but one comparison, aerobic fitness was associated with a highly significant reduction in pressor response during Low-NE as well as High-NE. Plasma norepinephrine was higher during the two aerobic phases; platelet catecholamines and plasma epinephrine showed no reliable association with fitness. Results for this subject support an attenuation of pressor response associated with aerobic conditioning. PMID- 2318564 TI - Comparison of some serum copper parameters in trained runners and control subjects. AB - The serum copper parameters were evaluated in 41 male trained runners and in a control group of 24 male subjects engaged in normal physical activity. In the runner group lower serum copper concentrations, lower serum ceruloplasmin biological activity, and higher serum ceruloplasmin levels were found compared with the control group. Reduced serum copper levels may affect the ceruloplasmin biological activity, even if the serum ceruloplasmin levels are higher. The results suggest that more attention should be paid to serum copper and ceruloplasmin in athletes. PMID- 2318565 TI - Potentiation of cytostatic but not cytolytic activity of murine macrophages after running stress. AB - The influence of physical exercise on the tumortoxicity of peritoneal murine macrophages (PMM) was investigated. The tumortoxic activity was discriminated into cytostatic and cytolytic effects. Cytostatic activity of PMM on tumor cells in vitro was studied using the proliferation assay of S-180 sarcoma cells. Cytolytic activity was monitored using the method of the slow form of antibody dependent cellular cytotoxicity (ADCC) on SW 707 tumor cells. After a single exhaustive running session an increased cytostatic activity of PMM was observed as compared to PMM of sedentary animals. In PMM mediated ADCC no difference was detected between trained and untrained animals. It is concluded that physical exercise is a complex stimulus for macrophages that, at least in parts, triggers their cytotoxic activity against tumor cells. PMID- 2318566 TI - Medical treatment and costs of sports-related injuries in a total population. AB - A prospective study of acute injuries from sports and physical exercise was carried out during 1 year in a total population of a municipality with 31,620 inhabitants. The medical treatment and the services required for the injuries have been calculated and related to the total consumption of medical care in the municipality. A total of 571 injuries (17% of all injuries) occurred in 28 different sports: 65% of the injured were males. Sports injuries accounted for 3% of all acute visits and there were altogether 1,083 outpatient visits, which yields a mean of 1.9 visits per injury. Related to the total consumption of outpatient visits to the five clinics in the municipality sports injuries also accounted for 3%. Forty-four patients were hospitalized; the proportion of inpatient care due to sports injuries was 0.7% and the mean length of stay in hospital 3.9 days. The total amount of sick leave compensated for sports injuries (3,477 days) was 1.2% of all days compensated in 1984. The overall mean cost per injury was US$ 335. Individual sports (motorcycling, downhill skiing and equine sport) were by far the most costly in the Falkoping survey, the dearest of the team sports ranking only fifth (handball followed by soccer). PMID- 2318567 TI - Function testing in patients with old rupture of the anterior cruciate ligament. AB - Fifteen patients with isolated old rupture of the anterior cruciate ligament (ACL) were examined to judge their functional disability. The following basic factors were used for evaluation: thigh muscle strength testing, stabilometry in a one-leg stance with straight and flexed knee, gait analysis, performance tests, knee function score, activity grading scale, and clinical joint laxity tests. We found that these rehabilitated patients mainly had impaired performance in those tests which greatly stressed the knee joint's sagittal stability. One-leg hop length was impaired for the injured limb. This group of patients had bilateral impairment of postural control compared with a reference group. This dysfunction was not revealed when comparing limbs. A derotation brace (ECKO) had neither a positive nor a negative effect in the tests. Different aspects of knee function evaluation are emphasized. Some of the altered functions are suggested to be due to central adjustments of motor control. PMID- 2318568 TI - Partial rupture of the pectoralis major muscle in athletes. AB - Partial rupture of the pectoralis major muscle is quite a rare event in sports traumatology and information about its treatment is lacking in literature. In this paper the long term effect of conservative non-surgical treatment in two body-builders and one shot-putter is discussed, who reported the partial rupture while performing bench lifts with barbells. Functional recovery was evaluated a few years after the injury (from 4 to 7) with an isokinetic dynamometer (Cybex II, Lumex INC N.Y.), measuring maximal shoulder adduction-abduction torques at different angular speeds (60, 180, and 300 degrees/s). The results were compared with those of five healthy athletes practicing either body-building or weight lifting. From the present study we conclude the following: the non-invasive treatment of a partial rupture of the pectoralis major muscle may produce almost complete functional recovery; in normal subjects adduction muscles are advantageous in comparison to the abduction ones. PMID- 2318569 TI - Gynaecomastia. Subcutaneous mastectomy with adipose tissue flap. AB - Eighteen patients with gynaecomastia were mastectomised over the last three years (September 1984 to September 1987) using a technique of modified subcutaneous mastectomy. This modification utilizes an axillary flat flap to fill in the defect resulting from excision of the breast tissue. All our patients had a very satisfactory post-operative cosmetic result. The frequent complications of breast excision, such as doughnut deformity, nipple necrosis, nipple flattening, inversion or loss of sensation, were not encountered in our series. The operative technique is described in detail, steps and a representative result are shown. PMID- 2318570 TI - Resection and radical lymphadenectomy for lung cancer: prognostic significance of lymphatic metastases. AB - From 1979 to 1987, 1103 thoracotomies were performed in patients with lung cancer: 824 (74.7%) radical resections, 141 (12.7%) palliative resections and 138 (12.5%) exploratory thoracotomies. Among the 965 patients who underwent resection, 539 patients were N0, 190 patients N1 and 236 patients N2. Among patients with N1 disease we observed more frequent hilar metastases in the more advanced tumors (p less than 0.05). In 84 out of the 232 N2 patients (36.2%; 13.4% of all patients) a skipping of all pulmonary sites was observed. The most commonly invaded mediastinal levels were the paratracheal nodes on the right and the aortic nodes on the left, followed by the subcarinal nodes. The greater the neoplastic involvement of pulmonary nodal sites, the higher the percentage of patients with N2 disease and the number of mediastinal levels with tumor cells (p less than 0.05). The 5-year survival rate is 60% for N0, 46% for N1 and 23% for N2 disease. There is no significant difference in survival between N2 and N1 + N2 patients. Metastatic involvement of both upper and lower mediastinal levels carries a poorer prognosis compared to involvement of one compartment only (p less than 0.02). Patients with findings of mediastinal metastatic involvement should be selected: studies on lymphatic metastases are useful to better establish surgical indications for N2 patients. PMID- 2318571 TI - EEA stapler in oesophagogastrectomies. AB - A retrospective study was conducted to evaluate the use of the EEA circular stapler in the construction of oesophagogastric anastomoses. Eighty five consecutive patients were subjected to oesophageal resections. There were 58 males and 27 females. The age ranged between 38 and 77 (mean 62) years and between 49 and 84 (mean 69) years respectively. In the first 19 patients the surgical approach was carried out via a Lewis' procedure and in the remaining 66 via a low left thoracotomy. The overall hospital mortality was 20%. Leakage related to mortality was found to be 4.7%. Mean operative time was estimated at a rate of 168 min (range: 120-360) and mean blood loss 434 ml (range: 250-1200). The mean postoperative stay was 15.3 days (range: 9-41). Benign anastomotic strictures occurred in 22% of the operated patients, all of whom responded well to dilation. By the aid of the EEA stapler, high and safe anastomoses can be carried out via a low left thoracotomy with acceptable morbidity and mortality. PMID- 2318572 TI - A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. XXIII. An injection technique for the treatment of idiopathic pruritus ani. AB - An injection technique for the treatment of idiopathic pruritus ani is presented. The technique was performed on 67 patients after failure of other methods to achieve permanent cure. The technique comprises injection of 5% solution of phenol in almond oil in the subcutaneous tissue of the rectal neck aiming at destruction of the "epithelial debris" which exists in this area and is considered the primary cause in idiopathic pruritus. Cure was obtained in 62 patients (92.5%). The remaining five patients underwent recurrence after a period of remission, and were cured after a second injection. The advantages of the present technique over others in common use are discussed. PMID- 2318573 TI - Three faces of midgut duplication. AB - This is an analysis of three unusual cases of gastrointestinal duplications seen over a two year period. They were all males aged eight and 48 hours, and 4 1/2 years. Two had cystic duplications; in one of them it was associated with a partially fixed cecum resulting in a volvulus, while in the second the duplication occurred in association with duodenal atresia and jejunal deletion. The third patient had a tubular malformation involving distal jejunum, whole of the ileum, and right side of the colon as far as its transverse level. It was also associated with duodenal stenosis and rectal atresia. Two cystic duplications had muscular coats separate from the normal bowel permitting complete excision. Clinical presentation and pathological anatomy are briefly considered and aspects of management are discussed. PMID- 2318574 TI - The effect of human chorionic gonadotropin (HCG) on restoration of physiological continuity of the spinal cord. A preliminary report. AB - The effect of human chorionic gonadotropin (HCG) hormone on restoration of physiological continuity of the spinal cord in rats was studied. After complete transection of the spinal cord at the midthoracic level eleven of these 21 rats in the study received HCG for six weeks. The other ten served as controls. At the end of six weeks amplitude of the cortically evoked motor At the end of six weeks amplitude of the cortically evoked motor action potential (CEMAP) was measured. The amplitude of the motor action potentials was significantly greater (P less than 0.02) in HCG treated rats. The study thus shows that HCG might help in the restoration of spinal cord function. PMID- 2318575 TI - Severe acute pancreatitis as the presenting symptom of primary sclerosing cholangitis: treatment by endoscopic insertion of a biliary stent. AB - Primary sclerosing cholangitis is a chronic, fibrosing, inflammatory condition of unknown origin of extra and intrahepatic bile ducts. Recurrent cholangitis and jaundice are the most frequent clinical manifestation in symptomatic patients. We report a patient with primary sclerosing cholangitis presented with recurrent attacks of acute pancreatitis. Such a combination was not reported till now in the literature. The acute pancreatitis was probably due to reflux of bile and sludge into the pancreatic duct due to stricture of the distal part of a common bile and pancreatic ducts. Endoscopic insertion of a biliary stent managed to prevent jaundice and recurrent pancreatitis. PMID- 2318577 TI - [Increased blood glucose concentration (hyperglycemia)]. PMID- 2318576 TI - Isolated profunda femoris insufficiency. AB - Because of rich anastomotic network profunda femoris artery is an important link between iliac and superficial femoral/popliteal circulation and thus isolated insufficiency of profunda is rare. It happened in the case reported herein when patient's own native common femoral artery and its bifurcation was excluded by aorto-femoral and femoro-popliteal bypass graft. Revasculatization of profunda ameliorated the problem. PMID- 2318578 TI - [Chronic fatigue and vomiting 1-1/2 years following diagnosis of hypothyroidism (Schmidt syndrome)]. PMID- 2318579 TI - [A 57-year-old patient with fatigue, proximally accentuated muscle weakness and patchy erythema]. PMID- 2318580 TI - [Cervical lymphadenopathy of unclear origin]. PMID- 2318581 TI - [Comment on the contribution by H. Lode and R. Schroder: "Possibilities for errors in endocarditis therapy"]. PMID- 2318582 TI - Herpes simplex virus glycoprotein D. Protective immunity against murine herpetic keratitis. AB - %$%%protective effect of glycoprotein D (gD) immunization against murine herpetic keratitis was investigated. gD was purified by affinity chromatography using anti gD monoclonal antibodies. Prior immunization with gD was shown to be effective in protecting mice from both the development of stromal keratitis and the spread of the virus to the central nervous system. The level of serum antibodies for virus neutralization, as well as for complement-dependent cytolysis (CDC), was significantly elevated in gD-immunized animals. Cellular immunity, however, was not detected. These results indicate that two antibody-mediated defense mechanisms--virus neutralization and CDC--were responsible for the protective effect observed in our study. PMID- 2318583 TI - Corneal epithelial barrier function after oxybuprocaine provocation in diabetics. AB - Corneal epithelial permeability for fluorescein was determined after provocation by a local anesthetic in 18 non-insulin-dependent diabetes mellitus (NIDDM) patients, 23 insulin-dependent diabetes mellitus (IDDM) patients, and 22 healthy controls to evaluate the corneal epithelial barrier function in diabetes. All volunteers had Oxybuprocaine instilled into one eye and saline into the other eye. The epithelial permeability values were determined by fluorophotometry, and the ratio between both eyes was calculated for each individual. The mean permeability values of the saline-instilled eyes in the diabetic patients did not differ significantly from those in the healthy controls (P greater than 0.2). The individual ratios between Oxybuprocaine- and saline-instilled eyes in the NIDDM and IDDM patients differed significantly from those in the healthy controls (mean ratios: 2.6, 1.9, and 1.0, respectively; P less than 0.002). The permeability ratios and the percentage glycosylated hemoglobin (HbAlc) were linearly correlated in the NIDDM patients but not in the IDDM patients (r = 0.73, P less than 0.001, and r = 0.09, P greater than 0.68, respectively). The results showed that the corneal epithelial barrier function in the diabetic patients was not impaired compared with that in the healthy controls. After provocation by a local anesthetic, the barrier function was impaired in the diabetic patients only. PMID- 2318585 TI - The patency of the retinal vasculature to erythrocytes in retinal vascular disease. AB - This paper presents the first evidence that in retinas with experimentally induced vascular disease some vessels contain only plasma. This was demonstrated by a histologic technique developed specifically to test the hypothesis that at some stage in retinal vascular disease, vessel patency to erythrocytes is lost before vessels close to plasma. Using this technique, we visualized three major components of the circulation at all retinal locations: the erythrocytes; the plasma as marked by the presence of 0.2-micron fluorescent microspheres; and all functioning endothelial cell nuclei, which were marked by the fluorochrome bis Benzimide. It was assumed that the distributions of the erythrocytes and small particles in retinal whole mounts reflected accurately the true in vivo distributions at the moment of circulation arrest. Postenucleation the retina can be viewed and photographed within 45 min of circulation arrest. The technique was used on normal rats and on rats induced with a fast-developing model of retinal vasculopathy. With this model, we demonstrated retinal vascular segments perfused by plasma but containing no erythrocytes with functioning endothelial cells in the vessel walls. This may mean that an early factor in some retinal vascular pathologies is tissue hypoxia caused by reduced erythrocyte perfusion. PMID- 2318584 TI - Reduction of basement membrane thickening in diabetic cat retina by sulindac. AB - Capillary basement membrane thickening is one of the earliest histologic lesions in diabetic retinopathy. Its pathogenesis is not understood; however, recent evidence suggests that aldose reductase may play a role. In this study, a new animal model, the diabetic cat, was used to determine whether retinal capillary basement membrane thickening occurred early in the course of hyperglycemia, and if so, whether it could be inhibited by sulindac, an aldose reductase inhibitor. Retinal capillary basement membrane thickness was significantly increased in diabetic cats compared to normal cats (114 +/- 15 vs 72 +/- 12 nm, mean +/- SD) [corrected]. Basement membrane thickness was significantly less in sulindac treated diabetic cats (93 +/- 9 nm) compared to the untreated diabetic cats (114 +/- 15 nm). In addition, quantitation of endothelial cells, pericytes, and contacts between endothelial cells and pericytes in electron micrographs revealed that they were not reduced in number in untreated diabetic cats compared to normal or sulindac-treated diabetic animals. PMID- 2318586 TI - Microperfusion studies on the permeability of retinal vessels. A new model demonstrating organic anion transport and a reabsorptive fluid flux. AB - We developed an experimental model to study the permeability of individual retinal vessels in vitro using microperfusion techniques adapted from kidney tubule studies. The retinal vessels were isolated by freehand dissection and mounted on a microperfusion apparatus. When inulin was perfused luminally, it was diluted to 80.2 +/- 2.3% of its initial concentration. However, no radioactive leak into the bath side was observed, suggesting that the dilution was due to fluid flux from bath to lumen. The dilution of fluorescein (81.9 +/- 3.8%) was in the same range as that of inulin, the reference marker. The extremely low lumen to-bath fluorescein flux, 0.5 +/- 0.9 X 10(-12) mol/min/mm, increased by 68% when probenecid was added to the perfusate and by 210% when probenecid was placed in the bath. The effect was concentration-dependent. When placed in the bath, fluorescein moved rapidly across the retinal vessel walls, accumulating in the lumen to concentrations 40 times higher than in the bath. This movement from bath to lumen, which was much higher (13.6 +/- 0.3 X 10(-12) mol/min/mm) than the lumen-to-bath fluorescein flux for the same fluorescein concentration, decreased by adding probenecid to the bath. The kinetics of this unidirectional movement of fluorescein were consistent with a saturable active transport process. The fluid flux from bath to lumen across the retinal vessels, which was 6.3 +/- 1.0 nl/min/mm for perfusion rates of 6.6 +/- 0.2 nl/min, was temperature-dependent and was coupled to the fluorescein transport. Fluorescein stimulated the fluid flux by 17% when added to the perfusate and by 60% when added to the bath, and this effect could be reversed by probenecid. Our results showed an active transport of fluorescein in the rabbit retinal vessels coupled with net fluid flux from outside the vessels into the lumen. PMID- 2318587 TI - Retinal pigment epithelium wound closure in vitro. Pharmacologic inhibition. AB - Early-passage bovine retinal pigment epithelium (RPE) cells were grown to confluence in 24-well plates, and a central defect was created mechanically in the monolayer within quadruplicate wells, sequentially over 9 days. Closure of the wounded area occurred by single-cell migration of elongated RPE cells from the edge of the wound and subsequent cell proliferation. Ten days after wounding, the cultures were fixed, stained, and photographed, and the residual wound area was quantified by computerized planimetry. Cell counts of unfixed cultures were determined with a Coulter counter. Wound closure was complete after 10 days. Using this technique, we assessed the response of RPE to various concentrations of 5-fluorouracil (5-Fu), colchicine (COL), and cytochalasin-B (CYT-B). 5-Fu (10 micrograms/ml) and COL (0.1 and 1 microgram/ml) inhibited migration and proliferation of RPE cells. CYT-B (5 micrograms/ml) inhibited migration. This model allows in vitro study of the response of RPE cells after loss of contact inhibition. The technique provides a quantitative model for assessing the dynamic capabilities of RPE cells in response to a localized mechanical defect and for assessing the pharmacologic modulation of these responses. PMID- 2318589 TI - Simultaneous pattern reversal ERG and VER recordings. Effect of stimulus field and central scotoma. AB - The effects of the sizes of the stimulus field and of an artificially created central scotoma on simultaneously recorded pattern-reversal electroretinogram (P ERG) and pattern-reversal visual-evoked response (P-VER) were investigated. With an increase in the stimulus field from 4 degrees X 4 degrees to 12 degrees X 12 degrees, the amplitude of the P-ERG increased steadily. The amplitude of the P VER also showed an increase up to a stimulus field of 6 degrees X 6 degrees or 8 degrees X 8 degrees, but showed no increase with further expansion of the stimulus field. A central scotoma, created by placing a square of black paper at the center of the 12 degrees X 12 degrees stimulus field, was increased from 4 degrees X 4 degrees to 10 degrees X 10 degrees by 2-degree increments. Amplitudes of both the P-ERG and the P-VER decreased with increasing central scotoma size. The P-VER decreased significantly with a 4 degrees X 4 degrees central scotoma. Although both the P-ERG and the P-VER were influenced by the overall stimulus field and the central scotoma, there was a distinct difference in their behavior. The P-VER showed saturation above a certain stimulus field size and, with a central scotoma of 4 degrees X 4 degrees, much more reduction than the P-ERG, suggesting that the P-VER depends more on the macular area than does the P-ERG. The P-ERG also exhibited a substantial macular dependency, which, however, was not as great as that of the P-VER. The greater macular dependency of the P-VER compared to the P-ERG, as observed in our study, reflects the larger anatomic representation of the macula at the higher visual level. PMID- 2318588 TI - Cefazolin levels after intravitreal injection. Effects of inflammation and surgery. AB - Cefazolin (2.25 mg) was injected into the vitreous cavity of phakic, aphakic, and aphakic/vitrectomized rabbits; inflamed eyes were compared to controls. Vitreous levels of cefazolin were determined at selected times from 2 to 48 hr, and the half-life was calculated. The effect of inflammation was to increase the half life or to reduce the rate of elimination of cefazolin from the vitreous cavity. The drug was cleared substantially faster from aphakic/vitrectomized eyes than from phakic or aphakic eyes. Vitreous levels of cefazolin were above the MIC for most common gram-positive organisms causing endophthalmitis in all study groups at 24 hr, but in only the phakic inflamed eyes and in the aphakic eyes with intact vitreous at 48 hr. PMID- 2318590 TI - The use of visual field indices in detecting changes in the visual field in glaucoma. AB - We present results from 64 glaucoma patients and glaucoma suspects followed up for a median period of 7.4 yr who had a median of seven examinations using Program 31 on the Octopus perimeter. The patients also had manual visual fields recorded on either the Tubinger or Goldmann perimeter during the same period. By examining all manual fields over the follow-up, we classified 37 patients as deteriorating and 27 as nondeteriorating by using predetermined field criteria which we believed to be clinically significant. In a masked fashion, the indices mean defect (MD) and corrected loss variance (CLV), in addition to the three cluster analysis indices SIZ, CLUS, and PCLUS were computed for each patient and regressed on time. When a significant positive index/time slope (P less than 0.05) was defined as indication of deterioration, all indices had remarkably poor sensitivities because their slopes did not reach statistical significance in the great majority of patients. When, regardless of statistical significance, positive slopes were defined as indication of deterioration and negative slopes as nondeterioration, the most sensitive index, PCLUS, still had a sensitivity of less than 65%. The indices were better in detecting the presence or absence of visual field deterioration in fields that were initially normal than in those that were initially abnormal. Since the testing modalities of manual and automated perimetry are different, our study was not designed to compare the sensitivity of one technique over the other. Our study does, however, demonstrate that the indices used currently may not be clinically reliable in the assessment of changes in the visual field. PMID- 2318591 TI - Time course of changes in aqueous protein concentration and flow rate after oral acetazolamide. AB - The coefficient of plasma protein entry into the aqueous humor, kin, was calculated in the human eyes from the aqueous protein concentration measured with a flare-cell meter and from the aqueous flow rate determined with fluorophotometry. The value of kin averaged 3.47 +/- 0.25 x 10(-5) min-1 (mean +/ SEM) in 12 eyes of six normal young volunteers. The time course of changes in aqueous protein concentration after oral administration of 500 mg acetazolamide was measured with a flare-cell meter in 24 eyes of 12 subjects. Aqueous protein concentration significantly increased from 2-10 hr postadministration with a maximum increase of 41 +/- 7% (mean +/- SEM) at 6 hr postadministration. Assuming that kin is not affected by the drug treatment, we calculated the time change of aqueous flow rate from that of aqueous protein concentration using the value of kin above. The calculated flow rate after the administration of acetazolamide decreased between 1.25 and 8 hr, with a maximum reduction of 40 +/- 11% at 1.75 hr postadministration. These measurements obtained with the flare-cell meter corresponded well to those obtained by fluorophotometry in a separate group of volunteers given the same treatment. It was shown that oral acetazolamide increases aqueous protein concentration, and that the time change of its effect on aqueous flow rate can be monitored by measuring aqueous protein concentration. PMID- 2318592 TI - 12(R)-hydroxyeicosatetraenoic acid, an endogenous corneal arachidonate metabolite, lowers intraocular pressure in rabbits. AB - 12(R)-hydroxyeicosatetraenoic acid (12(R)HETE) is an endogenous corneal epithelial arachidonic acid metabolite formed by the cytochrome P450 system and a potent inhibitor of Na(+)-K(+)-ATPase activity. We studied the effect of topically applied 12(R)HETE, either derived endogenously from corneal epithelium or synthetically prepared, on the IOP of the rabbit eye and compared it to its stereoisomer 12(S)HETE. Topical application of 1 microgram of biologically derived 12(R)HETE to both eyes of rabbits resulted in a marked reduction in IOP: a reduction of 4-7 mmHg occurred within 30-120 min. The IOP reduction effect of a single application of 12(R)HETE was long-lasting (9 days), whereas no effect on IOP was found for the vehicle control. Using synthetic compound, we demonstrated that the effect of 12(R)HETE on IOP is dose-dependent. Single topical application of 1, 10, and 50 micrograms of 12(R)HETE caused a reduction in IOP of 4, 6, and 12 mmHg, respectively. The stereoisomer, 12(S)HETE, did not have any effect on IOP at doses up to 5 micrograms. The IOP reduction effect of 12(R)HETE was not associated with hyperemia, appearance of flare, miotic response, or increased protein concentration of the aqueous humor. This study was the first to demonstrate that an endogenous inhibitor of Na(+)-K(+)-ATPase generated by the corneal epithelium potently and specifically lowers IOP in rabbits. Further studies are needed to elucidate the mechanism by which 12(R)HETE lowers IOP. PMID- 2318593 TI - A histologic study of lens regeneration in aphakic rabbits. AB - Lens regeneration occurs in New Zealand albino rabbits after endocapsular lens extraction, which leaves the anterior and posterior lens capsules relatively intact. Slit-lamp photography, histologic studies, and lens protein analysis confirmed the differentiation of lens fibers. In the current study, we performed a sequential analysis of the regenerating rabbit lens. After endocapsular phacoemulsification and irrigation/aspiration of the lens, rabbits were sacrificed at different time points for histologic evaluation. Similarities with embryologic development of the lens were evident, although in some sections, abnormal cellular proliferation occurred. By the 6th day after surgery, a monolayer of lens epithelial cells lined both the anterior and posterior capsules. At 1 month, the posterior epithelial cells had elongated, and nuclei had migrated anteriorly. At 2 months, lens cells were differentiating at the equatorial zone with gradual elongation, anterior migration of nuclei, and eventual loss of nuclei. PMID- 2318594 TI - Chromatic, spatial, and temporal losses of sensitivity in multiple sclerosis. AB - Chromatic, spatial, and temporal losses of sensitivity were measured in 15 eyes of 10 patients with recovered optic neuritis. Chromatic sensitivities (for both red-green and blue-yellow) were measured using color-mixture thresholds; the chromatic sensitivity loss was classified as "selective" if it was significantly greater than the achromatic loss. Spatial and temporal sensitivities were measured with contrast sensitivity functions and flicker modulation sensitivity, respectively; these losses were classified as selective if the losses at high (spatial or temporal) frequencies were significantly greater (or significantly less) than losses at low frequencies. All patients had central fixation and were optically corrected carefully. In 1 eye, selective losses of sensitivity for red green and blue-yellow were combined with a selective loss of sensitivity at high spatial (but not temporal) frequencies. This type of loss may indicate a selective loss of small axons in the optic nerve. The 8 other eyes that showed significant losses were generally nonselective in their chromatic, spatial, and temporal losses; this may indicate a nonselective loss of small and large axons. PMID- 2318596 TI - Esterification of retinol in lacrimal gland. Evidence for acyl-CoA:retinol acyltransferase activity. AB - Vitamin A is stored in cells as long-chain fatty acyl esters of retinol. Esterification in many tissues is catalyzed in part by acyl-CoA:retinol acyltransferase (ARAT). Since the lacrimal gland contains stores of retinyl esters, it was the goal of this study to determine whether the lacrimal gland contains ARAT activity. Rabbit lacrimal gland microsomes incubated with 3H retinol synthesized retinyl esters. The reaction rate was stimulated 30-fold in the presence of a fatty acyl-CoA generating system, producing a mixture of esters including retinyl laurate, retinyl linoleate, retinyl palmitate, and retinyl stearate as determined by reverse-phase HPLC. Retinyl palmitate was synthesized at 1944 pmole/mg protein/30 min, representing 50% of total ester synthesis, and this activity was directly proportional to microsomal protein concentration. In the presence of 180 microM 3H-retinol and 100 microM palmitoyl-CoA, retinyl palmitate was synthesized at 175-220 pmole/mg/min, and the reaction fit Michaelis Menten kinetics as a function of retinal concentration (theoretical Vmax = 329.4 pmole/mg/min). Lauroyl CoA and stearoyl CoA, but not linoleoyl CoA, were as effective as palmitoyl CoA as substrates for the reaction. The enzyme activity was inhibited by p-chloromercuriphenyl sulfonic acid and Na-taurocholate. The data show that the lacrimal gland synthesizes retinyl esters and that the characteristics of synthesis are consistent with the presence of acyl-CoA:retinol acyltransferase in lacrimal gland. PMID- 2318595 TI - Normal retinotopic mapping in human strabismus with anomalous retinal correspondence. AB - Burian proposed that a functional retinotopic remapping of the deviated eye on striate visual cortex may be the physiologic basis for the perceptual phenomenon of anomalous retinal correspondence (ARC) in human strabismus. This investigation searched for this type of retinotopic remapping in five esotropes and one exotrope with ARC by means of visual evoked potential (VEP) topographic mapping. Uniocular stimulation of the foveas (corresponding points) during binocular vision in a normal subject yielded identical VEP scalp topographies from each eye. Stimulation of anomalously corresponding points produced different VEP scalp topographies from each eye in the six strabismic subjects. Uniocular stimulation of the anatomic foveas of each eye (noncorresponding points) in a strabismic subject during binocular vision produced identical VEP scalp topographies. These results suggest that there is no significant functional binocular realignment of retinotopic mapping in the visual cortex of human strabismics with ARC. PMID- 2318597 TI - Visual acuity estimates in noncommunicative elderly persons. AB - The acuity card procedure has been shown to provide reliable grating acuity estimates in pediatric patients. The current study was conducted to determine the usefulness of this procedure in another group of persons in whom conventional acuity measurements are not possible, ie, nursing home residents who suffer from dementing disorders. Binocular visual acuity estimates were obtained in 13 cognitively impaired nursing home residents. Test sessions took 20-30 min each. Both test-retest agreement and inter-observer agreement of Teller Acuity Card (TAC) acuity estimates were good (within 0.5 octave for all residents), demonstrating that this procedure yields reasonable acuity estimates in noncommunicative nursing home residents. The authors stress the potential of this tool for nursing home administrators as well as for researchers. PMID- 2318598 TI - What's new in ob/gyn? Five Iowa physicians respond. PMID- 2318599 TI - Liability, restricted access of concern to ACOG. PMID- 2318600 TI - Pudendal anesthesia and the Iowa Trumpet. PMID- 2318601 TI - CME ethics, continued. PMID- 2318602 TI - A model program. PMID- 2318603 TI - Retinoids--dermatologists' drug of the decade. PMID- 2318606 TI - Royal Academy of Medicine in Ireland, Section of Biological Sciences. Summer meeting. 23rd & 24th June 1989. Abstracts. PMID- 2318604 TI - Legionella in Dublin hospital water supplies. AB - An environmental survey was carried out which consisted of periodic and random sampling of water tanks and showers in two large Dublin hospitals. Of the samples 5.3% yielded Legionella bacteria. Legionella pneumophila of serogroups 3, 5 and 6 were isolated from these sites with viable counts ranging from 3.0 x 10(2) - 2.5 x 10(3) c.f.u./litre. The implementation of periodic sampling may, however, not be a worthwhile exercise unless an environmental site has been associated with cases of legionellosis. Emphasis should be placed on the prevention of contamination of environmental sites with legionellae and on the development and implementation of protocols and procedures for the isolation of legionellae to gain the necessary expertise should an epidemiological survey be required. PMID- 2318605 TI - Heterotopic pancreas. AB - Heterotopic pancreas will be encountered infrequently by the surgeon causing symptoms or incidentally at laparotomy. To avoid confusion with carcinoma at laparotomy, local excision with frozen section diagnosis is recommended. Because frozen section diagnosis will not always be correct, clinical awareness of this condition at operation is also important. PMID- 2318608 TI - AIDS in our children--who cares for them? PMID- 2318607 TI - Induction of labour postdates in primiparae using vaginal prostaglandin tablets. AB - The management of pregnancy after 40 completed weeks remains controversial because induction of labour has been, in the past, associated with an increase in the incidence of caesarean section. This study examined the use of vaginal prostaglandin tablets for the induction of labour in selected primiparae after forty one weeks of pregnancy. The outcome of prostaglandin induction in 118 consecutive patients was compared with the outcome in 90 consecutive patients who went into labour spontaneously at the same gestation before induction could be undertaken. The active management of labour was applied in both groups and, therefore, the management of labour was strictly standardised. There was no difference between the two groups in the mode of delivery. Nor was prostaglandin induction associated with an increased incidence of prolonged labour. In selected primiparae, the cautious use of vaginal prostaglandin tablets can induce labour successfully postdates without increasing the complications of labour. A larger study is required to examine the effects of the induction of labour at this gestation on the fetal outcome. PMID- 2318609 TI - Estate of Longeway. PMID- 2318610 TI - In the matter of Joelle Rosebush. PMID- 2318611 TI - Torsades de pointes as a complication of bradyarrhythmias. PMID- 2318612 TI - Acute gallbladder infection with pneumococcal septicemia. PMID- 2318613 TI - Therapeutic approach to pericarditis in uremia. PMID- 2318614 TI - Angiotensin converting enzyme inhibitors in modern treatment of hypertension. PMID- 2318615 TI - The health diary as a source of information on kibbutz morbidity. AB - This study explores the use of health diaries as a source of information of general morbidity and health behavior among kibbutz residents. Two diary formats were randomly assigned to 76 families. Diary I (HDI) required daily responses concerning all health events for each family, even if no events occurred. Health diary II (HDII) required responses only on those days when health events occurred. The results were compared with the kibbutz clinic records. The compliance rate in this study was 72%. HDI demonstrated a high symptom-reporting rate compared with other populations studied. HDI families made an average of 4.5 visits to physicians and 9.7 to nurses during the year. HDI showed a higher validity than HDII. The advantage of the health diary lies primarily in its sensitivity to symptoms. Criterion validity, measured in terms of sensitivity, indicated that HDI was more than three times more sensitive than the nurse's log, but about equally sensitive as the physician's records. PMID- 2318616 TI - The Moshe Prywes lecture in medical education. Renewing medical education's social contract. PMID- 2318617 TI - The ethics of home care: autonomy and accommodation. PMID- 2318618 TI - On being ethical in unethical places: the dilemmas of South African clinical psychologists. AB - Practicing under the social and economic conditions created by apartheid, South African clinical psychologists face the task of questioning both the traditional values and the traditional social role of their profession. Dilemmas of trust, confidentiality, and professional competence highlight the limits of professional ethical codes. PMID- 2318620 TI - The heart, the gut, and brain death in Japan. PMID- 2318619 TI - HIV and pregnancy. AB - Testing women of childbearing age for HIV infection and disclosure of HIV status should be examined from three interlocking perspectives--women's personal concerns, the interests of caregivers, and those of the community. In the absence of specific objections, testing for HIV infection should be considered a routine procedure in prenatal care. PMID- 2318621 TI - No decision on Cruzan? PMID- 2318622 TI - C-section for organ donation. PMID- 2318623 TI - China: moral puzzles. PMID- 2318624 TI - Thailand: refining cultural values. PMID- 2318626 TI - The adolescence of ethics committees. PMID- 2318625 TI - The Philippines: a public awakening. PMID- 2318627 TI - Ethics committees and cost containment. PMID- 2318628 TI - How many hours? PMID- 2318629 TI - Is there a place for lawyers on ethics committees? A view from the inside. PMID- 2318630 TI - The Philadelphia story. PMID- 2318631 TI - Science as an ethical vocation. PMID- 2318632 TI - What about the family? AB - The prevalent ethic of patient autonomy ignores family interests in medical treatment decisions. Acknowledging these interests as legitimate forces basic changes in ethical theory and the moral practice of medicine. PMID- 2318633 TI - Inviting clinicians to kill... [. PMID- 2318634 TI - Geriatric medicine contribution in acute medical wards--a follow-up study. PMID- 2318635 TI - Comparison of acceptability by general practitioners of word processor and conventional discharge letters. AB - The potential use of word processor discharge letters in a district general hospital was investigated. A structured word processor type of letter was evaluated and compared with three conventional letters of varying length and detail by means of a questionnaire sent to 104 general practitioners (GPs) and trainees. The structured letter proved both generally popular and acceptable. The use of this letter format would reduce delays in communication between hospital and family doctor after patient discharge. PMID- 2318636 TI - On collaboration: reflections on the preparation of an inter-disciplinary research proposal. PMID- 2318637 TI - Development of health services research applications. PMID- 2318638 TI - A window on Scotland's health. PMID- 2318639 TI - [Lymphangioma circumscriptum cysticum following surgical and radiologic therapy]. AB - Four cases of lymphangioma circumscriptum cysticum are reported that developed 3 43 years after surgical or radiological therapy. Clinically, recurrent vesicles occurred in the treated areas. Manifest lymphatic edema was observed in only one case. The histologic picture showed papillary ectatic lymph vessels with no indication of proliferation or malignancy. Because of the postoperative tendency to recidivism, extensive excisions are not indicated. Manual lymph drainage was found to be effective. PMID- 2318640 TI - [CHILD syndrome in a mother and daughter]. AB - A 15-year-old girl with the typical signs and symptoms of the CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) is described. Associated ipsilateral anomalies included systematized hypotrichosis, fused vertebrae, hemivertebrae, pelvic hypoplasia and renal agenesis. During a careful inquiry, her mother reported that during her own adolescence she had linear ichthyosiform skin changes localized in 3 different regions of her body. These plaques had disappeared spontaneously in early adulthood, leaving permanent lesions in the form of hairless streaks and a dystrophic fingernail. Hence this is the first report of a mother-to-daughter transmission of this genodermatosis, lending further support to the proposed concept of X-linked dominant inheritance with lethality for male embryos. We conclude that the mother of a girl suffering from the CHILD syndrome cannot be considered to be unaffected unless a meticulous examination of her skin and bones has ruled out even minimal signs of involvement. PMID- 2318641 TI - [Malignant melanoma of the penis]. AB - In this paper the authors report on four of their own patients suffering from malignant melanoma of the penis, and the recent literature is reviewed. Growth of pigmented lesions and bleeding are the most important clinical symptoms. Malignant melanomas of the penis are often acrolentiginous melanomas; they occur predominantly in older patients and progress more rapidly than malignant melanomas of the common integument. PMID- 2318642 TI - [Pustular arthro-osteitis. Pustulosis palmaris et plantaris with arthritis of the sternoclavicular joint]. AB - A 26-year-old female patient presented with pustulosis palmaris et plantaris simultaneously with arthritis of the sternoclavicular joint. This association is described as an entity and is called pustulotic arthroosteitis in the Japanese literature, as well as in publications from Scandinavia. To our knowledge, this is the first observation in the Federal Republic of Germany. PMID- 2318643 TI - [Gardner syndrome]. AB - A case of Gardner syndrome associated with alterations of the skin and bones and precancerous gastrointestinal polyposis is presented. Particular interest attached to the extension of polyposis to the entire digestive tract, the early appearance of abdominal signs attributable to the polyposis, and - as new symptoms - polycystic lung and widespread superficial naevus lipomatosus. PMID- 2318644 TI - [Melkersson-Rosenthal syndrome in Curschmann-Steinert dystrophia myotonica]. AB - We report the case of a 52-year-old female patient who suffered both from myotonic dystrophy (Curschmann-Steinert disease) and Melkersson-Rosenthal syndrome. Both syndromes showed the full-blown clinical features as well as the typical histology. In addition to the possibility that the appearance of the two syndromes together was a mere coincidence, we also consider the possibility that there was a hereditary diencephalic disorder present that linked together some of the minor manifestations of both syndromes. PMID- 2318645 TI - [Experiences with oxytetracycline treatment of non-gonorrhea urethritis caused by Ureaplasma urealyticum]. AB - In a retrospective study, the efficacy of tetracycline therapy was assessed in 48 men with non-gonococcal urethritis who only harbored Ureaplasma urealyticum in their urethras. After 2 weeks of therapy with 2.0 g oxytetracycline per day, U. urealyticum was still found in the urethra of 8 patients (17%). Urethritis was still present in 8 patients (17%) according to clinical criteria and in 11 patients (23%) according to microscopic findings. The persistence of U. urealyticum in the urethra did not correlate with the persistence of urethritis to a statistically significant degree. Therapy compliance, antibiotic resistance in a few cases, reinfections in 2 cases and a special host-parasite relationship are discussed with respect to the treatment failures. PMID- 2318646 TI - [Cutaneous leishmaniasis: treatment with cryotherapy and intramuscular injections of meglumine antimonate (glucantime)]. AB - A 37-year-old female patient with cutaneous leishmaniasis of the helix of the left ear is reported. The diagnosis was based on her past history, clinical appearance and histological examination (detection of Leishman-Donovan bodies). Initial cryotherapy failed to cure the lesions completely. Treatment with intramuscular injections of meglumine antimonate (Glucantime) was successful. The discussion focuses on the pathophysiology, diagnosis and therapy. PMID- 2318647 TI - Community health advocacy for racial and ethnic minorities in the United States: issues and challenges for health education. AB - The 1985 Heckler report on Black and minority health clearly demonstrated that minority groups suffer excess morbidity and mortality directly related to social inequalities. Subsequently, improving the health status of minorities must go beyond personal health care delivery and address the broad issues of health policy. There is increasing evidence that wide public support is mounting to address many of the major health problems facing minority groups. In order to modify health behavior of minorities, health educators must recognize that traditional health promotion activities, focused on voluntary personal behavior change, may not be effective in reducing morbidity and mortality rates. Efforts to improve the health status of minorities must include an aggressive health policy dimension. Personal behavior change effort without an equal or greater emphasis on policy change is tantamount to blaming the victim. A health educators become increasingly aware of the political nature of health issues, it will be necessary to examine the health status of ethnic and racial minority populations from the perspective of community health advocacy. PMID- 2318648 TI - Tribal rituals in Boston. PMID- 2318649 TI - Characteristics of volunteers who deliver health education and promotion: a comparison with organization members and program participants. AB - The use of volunteers in this culture for community health endeavors is an understudied area. Yet, there may be many potential benefits for utilizing volunteers in the delivery of community health education and promotion. Volunteers may have more immediate access to their peers, credibility, and familiarity with the cultural environment and organization elements. An assumption of volunteer use is that persons drawn from a targeted organization (or community subgroup) will be like other members. Such an assumption, however, should be confirmed or disproved. This article compares a sample of volunteers to a sample of members from organizations from which the volunteers were recruited. The paper also compares the volunteers to a sample of program participants. The participants were persons to whom the volunteers delivered CVD prevention programming and, in most cases, were also organization members. Collectively using the variables under investigation, multivariate analyses of variance found that the volunteers were different from the organization members, and different from program participants. To assess differences between the samples on each individual variable, univariate tests were conducted stratifying the samples by age. Statistically significant differences were found regarding organization activity, formal education level, success with past health habit change, health self-assessment, occupation, gender, and marital status. PMID- 2318650 TI - Through the looking glass: the opportunity for a unified vision for SOPHE. 38th SOPHE presidential address. PMID- 2318651 TI - An outcome evaluation of project model health: a middle school health promotion program. AB - This article reports findings from the outcome evaluation of Project Model Health (PMH), an intensive in-school health promotion program for middle school students. Promising prevention strategies identified in past research based on social influences theory were combined in PMH, targeting multiple health behaviors in the areas of nutrition, marijuana use, tobacco use, drinking and driving, and sexuality. Results reported in this paper are based on an experimental group of 115 eight graders who were exposed to the 32 hour program, taught by college-age "role models." The evaluation included both an extensive qualitative process evaluation and a quasi-experimental outcome evaluation. The outcome evaluation used both a prior year's cohort and students from a similar untreated school for comparison purposes. While an immediate post-test showed only inconsistent results, a 20-month follow-up resulted in clear positive outcomes for experimental students on measures of cigarette smoking and improved food choices, and ambiguous but positive results on rates of intercourse. Limitations of the methodology (nonexperimental assignment to conditions, reliance only on self-report data) are such that further more rigorous testing of this program model is called for. However, PMH shows significant promise as an effective adolescent health promotion approach. PMID- 2318652 TI - Towards an understanding of risk behavior: an AIDS risk reduction model (ARRM). AB - This report presents a three-stage model (ARRM) that characterize people's efforts to change sexual behaviors related to HIV transmission. ARRM focuses on social and psychological factors hypothesized to influence (1) labeling of high risk behaviors as problematic, (2) making a commitment to changing high risk behaviors, and (3) seeking and enacting solutions directed at reducing high risk activities. The proposed model integrates important concepts from prior behavioral medicine and human sexuality studies, specifies their differential import to achieving the goals associated with each stage of the model, and denotes factors hypothesized to influence people's motivation to continue the change process over time. Current findings are discussed within this three-stage model and directions for further research are suggested. Recent findings from our ongoing studies of gays and heterosexuals in San Francisco are presented. PMID- 2318653 TI - Development of the Children's Health Ratings Scale. AB - Following pilot testing, the 17-item Children's Health Ratings Scale was group administered to approximately 1,200 fourth- through sixth-grade students. The internal consistency reliability, concurrent validity, and construct validity of the scale were examined utilizing various statistical methods, including calculation of the alpha coefficient, factor analysis, and other correlational techniques. The scale was found to be reliable with an alpha coefficient of .83. Concurrent validity was supported by the finding that higher scale scores were associated with higher ratings on a single, general health item and with lower ratings on single items concerning pain, health worry, and the presence of sickness. Correlations between scores on the Children's Health Ratings Scale and sex, grade level, and a measure of response bias were of low magnitude and presented no serious threat to instrument validity. Five factors were identified for interpretation during factor analysis. A post hoc validity study compared the mean scale scores of a group of asthmatic children and a subsample from the scale development study. Suggestions for further study are presented. PMID- 2318654 TI - A systematic effort to reduce smoking at the worksite. AB - Smoking control is a key element of worksite health promotion. This three-stage study in a large state human services agency included a baseline survey, an assessment of the effects of competition on recruitment to a self-help cessation program, and examination of the outcome of the cessation program. In stage 1, scales for measuring smoking-related attitudes and the social environment were developed and used to study norms for smoking. Regression analysis was used to ascertain correlates of smokers' intentions to quit and to join a self-help program and non-smoker assertiveness. In stage 2, an evaluation using a quasi experimental design indicated that competition was moderately effective in increasing the recruitment of all employees to the Great American Smoke-Out (70 vs. 17%) and of smokers to a self-help cessation program (28 vs. 6%). In stage 3, the self-reported quit rate at the end of the program was 28% and the biochemically-verified six months' cessation rate was 7%. Efforts are needed to strengthen, using ethical means, the norms for not smoking at the worksite and to increase both the recruitment to and the effectiveness of smoking cessation programs. PMID- 2318655 TI - Functional assessment of elderly patients after percutaneous aortic balloon valvuloplasty: New York Heart Association classification versus functional status questionnaire. AB - Monitoring functional status in patients with cardiac disease has traditionally been done by using the New York Heart Association (NYHA) classification system. For various reasons, we found the NYHA system difficult to apply to elderly patients. We proposed that the functional status questionnaire (FSQ), which measures the ability to perform tasks, would more accurately assess the functional status of the elderly. In a study in 37 patients with a mean age of 76 years, who had aortic stenosis, we measured FSQ and NYHA scores at baseline, 1 month and 3 months. The difference in questionnaires was evident by the 3-month measurement. Individual patients were better evaluated by the FSQ. Six patients had an FSQ score of less than 72 (suggesting severe functional impairment) at 3 months but only two patients gave symptoms scored as NYHA class III or IV (cardiac disability). Five of six patients had a recurrent cardiac event subsequent to the 3-month follow-up. Changes in functional performance preceded symptomatic deterioration that was reflected only by the FSQ scores. The FSQ system more reliably predicted outcome than the NYHA system and appears to be a more useful tool in the evaluation of elderly patients with cardiac disease. PMID- 2318656 TI - Regaining control: the process of adjustment after myocardial infarction. AB - The purpose of this study was to examine the process of adjustment that individuals experience after having a myocardial infarction (MI). The study used a grounded theory approach. Interviews with 14 individuals who had an MI provided the major source of data. The findings of this study indicate that the process of adjustment after MI is variable and incorporates four stages. In each of these stages the individual focuses on the core process of regaining a sense of personal control. The first stage of the adjustment process involves attempts to defend oneself against a threatened loss of control. In the second stage, the individual struggles to come to terms with the MI. Throughout the third stage, numerous strategies are used to reestablish a sense of control. If control is reestablished the individual progresses to the final stage of adjustment. The hallmarks of the final stage include an acceptance of limitations, a refocusing on issues other than the MI, and a perceived sense of mastery. PMID- 2318657 TI - Reproducibility and accuracy of pulmonary artery pressure measurement in supine and lateral positions. AB - The reproducibility and accuracy of pulmonary artery (PA) pressures in supine versus side-lying positions were compared in two groups of intensive care unit (ICU) patients. Side-lying measurements were reproducible, accurate, and clinically acceptable for surgical ICU patients, but not for medical ICU patients. The inconsistency was partly explained by the reference points used for transducer releveling in lateral positions. Surgical ICU used the fourth intercostal space and dependent midaxillary line; medical ICU used the fourth intercostal space and sternum. Reversing the leveling procedure in each ICU reduced surgical unit accuracy to an unacceptable level; medical unit accuracy was increased but was still too low for clinical acceptance. Further research is needed to identify appropriate anatomic reference points for transducer releveling in the side-lying position and to clarify which patient groups may be safely monitored by using this position. PMID- 2318658 TI - Support of the growth hormone-somatomedin system to facilitate healing. AB - We describe the role of growth hormone and somatomedins in the process of healing and discuss how nutrition, sleep, and stress affect this process. Nursing therapies to support healing are proposed and directions for further research are suggested. PMID- 2318659 TI - Dyspnea during hospitalizations for acute phase of illness as recalled by patients with chronic obstructive pulmonary disease. AB - With use of a qualitative research approach, a study was conducted to explore the phenomenon of dyspnea from the point of view of patients with chronic obstructive pulmonary disease. During a nonacute phase of their illness, 96 adults with chronic bronchitis or emphysema were asked in semistructured interviews to recall their feelings associated with sensations of shortness of breath during hospitalizations for the acute phase. Through content analysis, accounts of different subjects were compared, and several themes were isolated that dominated the dyspneic experience. The themes were fear, helplessness, loss of vitality, preoccupation, and legitimacy. Each theme was expanded by integrating accounts of dyspnea previously reported in the literature with the field study data. Substantiated descriptions of the five themes are presented to sensitize nurses to patients' perceptions of dyspnea and nursing behaviors during hospitalization for the acute phase of chronic obstructive pulmonary disease. PMID- 2318660 TI - French validation of the critical care family needs inventory. AB - This study is a contribution to the French validation of Molter and Leske Critical Care Family Needs Inventory (CCFNI). The importance of this validation study is based on the presumption that evaluation of family needs relies on the use of measures that are reliable and valid for a specific population. The preliminary validation of the French text of the CCFNI was carried out by back translation method of the French form into English by three translators. Then the final French version was selected. The study was conducted in the surgical intensive care unit of the University Hospital in Sherbrooke, Canada. The sample consisted of 207 voluntary subjects selected from adult members of the immediate family visiting a patient in the intensive care unit. The data collection was spread over a 10-week period. The French version of the CCFNI was given to subjects for self-reporting at the end of a 15-minute face-to-face interview. The reliability of the French version yielded 0.91 as Cronbach alpha coefficient. The Spearman-Brown split-half coefficient was 0.89, and the Guttman split-half coefficient was 0.88. Principal-component analysis and factorial matrices were used to examine the clustering structure of the French version of this instrument. PMID- 2318661 TI - Heart sound simulation: how useful for critical care nurses? AB - Forty critical care nurses participated in a 2-hour teaching program using a heart sound simulator to increase skill in recognition of heart sounds. Mean test scores increased 10 points from the pretest to the first posttest (t = 11.9, p = 0.0001), and this increase was maintained on the second posttest 3 weeks later. Medical intensive care unit and coronary care nurses scored higher than the other critical care nurses. There was a low correlation between recognition of sounds and years of critical care experience. The correlation between the subjects' self rating of knowledge of heart sounds and their actual skills was also low. These findings suggest that a similar teaching program might be useful for critical care nurses. PMID- 2318662 TI - Pseudomonas stutzeri synthetic vascular graft infection. PMID- 2318663 TI - Bioethics research in nursing and medicine. PMID- 2318665 TI - Program to deal effectively and safely with the nursing shortage. PMID- 2318664 TI - Non-Q wave versus nontransmural infarction. AB - The classification of myocardial infarction into transmural and subendocardial types has previously been based on the presence or absence of abnormal Q waves. The pathologic anatomy of necrosis in myocardial infarction does not necessarily correspond to these electrocardiographic criteria. It is therefore more appropriate to describe these infarcts as Q wave or non-Q wave myocardial infarctions. The importance of this classification is underscored by their clinical and pathologic differences and the tendency for more serious prognosis in the non-Q wave infarcts. PMID- 2318666 TI - Concerning the issue of slow, partial, and limited codes. PMID- 2318667 TI - Hemofiltration: an alternative to dialysis. PMID- 2318668 TI - [Neuro-otologic criteria in the diagnosis of tumor-induced hearing disorders. Studies of 300 patients with acoustic neuroma]. AB - Recently, costly technical procedures have been used for the diagnosis of a retrocochlear hearing loss. Electrophysiological methods such as ERA, electrocochleography and promontory tests, and imaging procedures such as CT and MRI have been widely used. Here we demonstrate the diagnostic value of conventional audiometry in retrocochlear lesions. As the clinical audiometric picture shows, a retrocochlear lesion is based on electrophysiological conduction phenomena. The threshold tone decay, absence of stapedius reflex, reduced speech discrimination and ERA findings with electric response decay and synchronization disorders within the brain stem are particularly significant. PMID- 2318669 TI - [Electrocochleography possibilities in the differential diagnosis of hydrops and neural hearing loss]. AB - Enhancement of the click-evoked summating potential causing a pathological summation to compound action potential ratio (SP/CAP) in patients with endolymphatic hydrops has been described by several groups. An increased SP/CAP ratio is found also in some patients with a tumour of the cerebellopontine angle. The study of further parameters of the SP/CAP complex, such as the CAP latency and the width of the complex, permit an electrocochleographic differentiation between both forms of hearing loss. The N2 amplitude showed no diagnostic significance. PMID- 2318670 TI - [Sudden unilateral deafness and geotropic positional nystagmus--a special form of acute cochleo-vestibular disorders?]. AB - Three patients with complete sudden unilateral hearing loss suffered from delayed vertigo and presented a strong geotropic positional nystagmus during the evolution of their disease. Significant direction-fixed spontaneous nystagmus was absent, although two of the three patients had markedly decreased caloric responses on the diseased side. These findings are considered as a special form of peripheral cochleovestibular disorder restricted mainly to the cochlea and the otolith organs. PMID- 2318671 TI - [Intracranial complications of inflammatory ear diseases]. AB - Acute and chronic ear infection can lead to intracranial complications, brain abscess and meningitis being the most serious. The clinical picture, diagnosis and therapeutic guidelines are discussed. The important role of interdisciplinary management is emphasised by a case report. PMID- 2318672 TI - [Inner ear hearing loss following cerebrospinal fluid puncture: a too little appreciated complication?]. AB - Lumbar puncture for myelography, spinal anaesthesia and aspiration of cerebrospinal fluid is a very common procedure. Although it has been known for a long time that hearing impairment may be a late complication, only a few case reports have been published, and not all have included audiograms. We present nine cases of hearing loss following myelography, lumbar puncture and spinal anaesthesia. It appears likely that this rare complication arises only in subjects with a wholly or partially patent cochlear aqueduct, allowing loss of perilymphatic fluid into the cerebrospinal space. Hearing loss was seen in eight of nine patients in the lower frequencies and in six of nine patients on both sides. Hearing recovered in six of nine patients. Transient hearing loss may occur more often than is generally assumed, and the symptom can remain unnoticed. Since not all of these hearing losses proved to be fully reversible, we suggest to inform patients about this complication for medico-legal reasons. PMID- 2318673 TI - [Conservative and functional treatment of the cervical spine]. AB - Physiotherapy is the basic treatment for functional disorders of the cervical spine. The aspects of good physiotherapy are demonstrated and a plea is made that ENT surgeons should be trained in manual therapy. PMID- 2318675 TI - Complotypes in pemphigus vulgaris: differences between Jewish and non-Jewish patients. AB - Haplotypes of alleles of the major histocompatibility complex (MHC) complement genes BF, C2, C4A, and C4B are inherited as single highly polymorphic genetic units called complotypes. There are about a dozen complotypes with frequencies above about 0.01 in Caucasians. In the blistering disease pemphigus vulgaris, the complotypes SC21 and SB45 were found to be markedly elevated in patients compared with general Caucasian controls. The SC21 increase was in Ashkenazi Jewish patients exclusively (relative risk = 17 in that population), whereas SB45 was found solely in non-Jewish Caucasians (specific population relative risk = 57). Although these are unusually high relative risks, it is most unlikely that these complotypes represent susceptibility genes for pemphigus vulgaris. Rather, it is probable that they mark extended major histocompatibility complex haplotypes with fixed DNA so that independent examples in the population have the same alleles. It is likely that it is the class II genes on these haplotypes that confer susceptibility. PMID- 2318674 TI - Sequence analysis and oligonucleotide genotyping of HLA-DR"JX6", a DR"blank" haplotype found in the Japanese population. AB - We analyzed one of the HLA-DR"blank" haplotypes found in the Japanese population using serologic studies, sequence determination, and genotyping with sequence specific oligonucleotide (SSO) probes. The DR"blank" haplotype, designated DR"JX6", segregated in a family in association with the DRw52 and the DQw7 specificities. The cDNA and genomic DNA of the DRB1 gene originating from the DR"JX6" haplotype were amplified enzymatically and sequenced after cloning into a plasmid vector. The amino acid sequence of the first domain in the DR beta 1 chain of the DR"JX6" haplotype was different from those of other DR haplotypes sequenced so far, but in the first hypervariable region, the sequence was identical to those of the DRw11, DRw13, DRw14, and DRw17 haplotypes. SSO probes were synthesized on the basis of the DR"JX6" haplotype sequence as well as known sequences of the DRB1, DRB3, and DRB4 genes of other DR haplotypes. These SSO probes were used for the genotyping of Japanese donors whose DRB genes were amplified enzymatically and found to show a hybridization profile that was consistent with the results of serologic studies on the DR"JX6" haplotype. PMID- 2318677 TI - A second opinion on geriatric training programs. PMID- 2318678 TI - All AIDS patients should have access to zidovudine (AZT) PMID- 2318676 TI - Full-length DQ beta cDNA sequences of HLA-DR2/DQw1 subtypes: genetic interactions between two DQ beta loci generate human class II HLA diversity. AB - Two-dimensional gel electrophoresis of DQ molecules from three different Dw subtypes (Dw2, Dw12, and Dw21/FJO) of the HLA-DR2/DQw1 haplotype reveals that one alpha beta heterodimer of DQ molecule is expressed by each subtype and the DQ beta chain is electrophoretically variable among the three DR2/DQw1 subtypes. We have constructed cDNA libraries from the same homozygous typing cells used in the two-dimensional polyacrylamide gel electrophoresis analyses (HTC VYT for Dw2, HTC DHO for Dw12, and HTC FJO for Dw21/FJO) and isolated DQ beta cDNA clones with full-length coding sequences for each subtype. The deduced amino acid sequences show that the DQ beta chains of these three DR2/DQw1 subtypes are highly polymorphic and confirm their electrophoretic heterogeneity: for a mature protein of 229 amino acids, they differ with each other by 10-17 amino acids in the first domain and by 3-7 residues in the C-terminal sequence. Comparison among the available DQ beta sequences representing the four major DQ specificities (DQw1, DQw2, DQw3, and DQw4) in the DQ subregion as defined by serologic method suggests that (1) DR2,Dw2,DQw1 and DR3,DQw2 haplotypes probably interact with each other to generate the DQw3 and DQw4 beta alleles and (2) an evolutionary scheme may be proposed to relate the various beta alleles of the four major DQ specificities. PMID- 2318679 TI - Radiologic appearance of stress fractures. AB - The large numbers of Americans involved in sports and physical activities have made stress fractures a more common injury to the lower extremities than before. Presented are the typical radiographic and scintigraphic appearances of stress fractures and the appropriate medical imaging with which to diagnose this entity. PMID- 2318680 TI - Menses due to endometriosis in a woman following hysterectomy. AB - Endometriosis can present in a variety of ways and must be considered in women of reproductive age who have complaints of pelvic or abdominal origin. It can be a difficult diagnosis to make, and it can mask the signs and symptoms of various other disease processes. The condition leads to fibrosis and adhesion formation, and is a common cause of infertility and spontaneous abortion. This report highlights the clinical and pathologic findings in a woman with pelvic endometriosis and discusses current concepts in treatment. PMID- 2318681 TI - Congenital dacryocystocele with intranasal extension: correlation of computed tomography and magnetic resonance imaging. AB - A case of dacryocystocele with intranasal extension is described by magnetic resonance imaging (MRI) characteristics, which are correlated with the appearance on computed tomography (CT) scans. Computed tomography and MRI are equally sensitive in detecting dacryocystocele. Magnetic resonance imaging has the advantages of characterizing the cyst contents, allowing multiplanar imaging without the need for manipulation of the patient, and the absence of radiation exposure. Computed tomography has the advantage of detecting bone changes involving the bony nasolacrimal canal. Clinically, these abnormalities usually resolve spontaneously and only rarely require surgical intervention. PMID- 2318682 TI - Actinomycosis: an unusual complication following appendicitis. AB - We present a report of a case of retroperitoneal actinomycosis 3 years after appendectomy for a ruptured appendix. Actinomycosis is an unusual infectious disease that occasionally occurs after enteric perforation. The literature is reviewed, and the pathogenesis, diagnosis, and treatment are discussed. PMID- 2318683 TI - CT simulator: a new 3-D planning and simulating system for radiotherapy: Part 1. Description of system. AB - A real time CT-linked 3-D treatment planning system, called a CT simulator, has been developed. The basic system consists of a CT scanner, a multi-image display component, a treatment planning device with real time visual optimization, and a laser beam projecting component. All the components are connected on line. The system can be conveniently used for 3-D planning and simulation for radiation therapy within a reasonably short period of time. PMID- 2318684 TI - CT simulator: a new 3-D planning and simulating system for radiotherapy: Part 2. Clinical application. AB - We have performed radiotherapy treatment planning (RTP) with a new system called CT simulator in 72 patients. With the system, RTP is performed with the patient lying on the CT couch within a short period of time. All the CT images scanned were immediately transported to the multi-image monitors and to the treatment planning device. Radiotherapy treatment planning could be performed not only at the beam center but also at any CT slice. Using a laser-beam field projector, field outlines were drawn over the patient's skin. In clinical use, the system was useful for cases in which a target lies adjacent to dose limiting organs, cases with a complicated target shape, cases with complicated dose distribution curves, and cases treated with tangential fields. This system enables us to make optimum use of CT information and to make accurate 3-dimensional treatment planning programs. PMID- 2318685 TI - Fibromatoses: from postsurgical surveillance to combined surgery and radiation therapy. AB - The results of management of two groups of patients with musculoaponeurotic (desmoid tumors) and plantar fibromatoses seen at Massachusetts General Hospital (MGH) during the period 1970-1985 are examined: (a) 26 patients who had had surgical resection for their primary fibromatosis but whose surgical margins were positive and who received no further treatment; and (b) 24 patients who were treated for their primary or recurrent fibromatosis by radiation alone or combined with surgery. For the 26 patients who were only observed, despite the positive surgical margins, 9 have recurred; the actuarial continuous local control rate at 5 years was 68% (a median follow-up of 70 months). Five patients had gross disease left after surgery and all of them failed. Seventeen of 21 patients who had grossly complete resection have local control; the four failures have been salvaged. This result supports the rationale for a no treatment but a thorough and close follow-up policy for patients with positive margins after grossly complete resection of a primary desmoid or fascial fibromatosis. There is no risk of metastasis in these patients and hence the effort toward a conservative policy which defers radiation merits interest and further study. Of the second group, 23 patients were treated for gross disease and one patient for microscopic disease after surgical resection. All of the 10 patients who were treated for primary desmoid tumor have local control. Among the 14 recurrent desmoid tumors there have been five local failures, after treatment by radiation alone or radiation + surgery. Three patients treated by radiation alone are currently scored as incompletely regressed tumors. Accordingly 16 of the 24 patients are scored as local controls without evidence of disease and 19 of the 24 are scored as local control (complete response or partial but stable response). PMID- 2318686 TI - Pineal region germinomas in childhood treatment considerations. AB - From 1967-1986, 21 children were treated for pineal germinoma, including 16 biopsy-proven, 2 biopsy non-diagnostic, and 3 metastatic unbiopsied (marker negative) patients. Ten of 18 (56%) biopsied patients underwent partial or sub total tumor resection. Twenty patients were irradiated, 19 of whom are alive. No irradiated patient died of progressive germinoma, but two patients relapsed in the spinal cord and required treatment intensification for salvage. Long-term survivors have significant morbidity. Determination of the minimum effective treatment remains the chief therapeutic challenge. PMID- 2318687 TI - Tumor necrosis factor as an adjunct to fractionated radiotherapy in the treatment of murine tumors. AB - Recombinant murine tumor necrosis factor (TNF) was investigated for its ability to increase the response of a murine mammary carcinoma to fractionated local tumor irradiation. When tumors in the leg of syngeneic mice grew to 8 mm in diameter (268 mm3), they were exposed to 3, 4 or 5 Gy gamma-rays daily for 10 days. Tumor necrosis factor was given 3 hr after each irradiation at a dose of 2 micrograms per mouse. Tumor growth delay was used as the endpoint. The effect of treatment with both agents combined was greater than the additive effect of the individual treatments. Tumor necrosis factor increased local tumor radiotherapy response by a factor of about 1.2, and by itself was effective in retarding the growth of both immunogenic and nonimmunogenic tumors. These experiments suggest that tumor necrosis factor in combination with radiotherapy may be beneficial for the treatment of cancer patients. PMID- 2318688 TI - Heterogeneity in tumor microvascular response to radiation. AB - Viable hypoxic cells have reduced radiosensitivity and could be a potential cause for treatment failure with radiotherapy. The process of reoxygenation, which may occur after radiation exposure, could increase the probability for control. However, incomplete or insufficient reoxygenation may still be a potential cause for local treatment failure. One mechanism that has been thought to be responsible for reoxygenation is an increase in vascular prominence after radiation. However, the effect is known to be heterogeneous. In this study, tumor microvascular hemodynamics and morphologies were studied using the R3230 Ac mammary adenocarcinoma transplanted in a dorsal flap window chamber of the Fischer-344 rat. Measurements were made before and after (at 24 and 72 hr) 5-Gy radiation exposure to assess microvascular changes and to explore possible explanations for the heterogeneity of the effect. There was considerable heterogeneity between tumors prior to radiation. Vascular densities ranged from 67 to 3000 vessels/mm3 and median vessel diameters from 22 to 85 microns. Pretreatment perfusion values varied by a factor of six. In irradiated tumors, conjoint increases in both vascular density and perfusion occurred in most tumors, although the degree of change was variable from one individual to the next. The degree of change in density was inversely related to median pretreatment diameter. Relative change in flow, as predicted by morphometric measurements, overestimated observed changes in flow measured hemodynamically. These results support that heterogeneity in tumor vascular effects from radiation are somewhat dependent on pretreatment morphology as well as relative change in morphology. Since changes in flow could not be completely explained by morphometric measurements, however, it is likely that radiation induced changes in pressure and/or viscosity contribute to the overall effect. Further work in this laboratory will investigate these hypotheses. PMID- 2318689 TI - The response of two human tumor xenografts to fractionated irradiation. The derivation of alpha/beta ratios from growth delay, tumor control, and in vitro cell survival assays. AB - A series of growth delay experiments was performed to derive alpha/beta ratios for two human neoplasms growing as xenografts in the hind limbs of NCr/Sed nude mice. The tumors were irradiated at 6 mm mean diameter under clamp-hypoxic conditions in one, two, four, or eight fractions, 2 fractions per day with a minimum intertreatment interval of 4 hr and a maximum overall treatment time of 3 days. The alpha/beta ratios derived for the high grade glioma U87 and the pharyngeal squamous carcinoma FaDu were 38 and 20 Gy, respectively. Comparably high values were derived from the same two tumors in a reanalysis of fractionated TCD50 data. The alpha/beta ratios were similarly high whether the TCD50 data were analyzed using the Full Effect plot or the Direct Method. For comparison, cell survival assays were performed on U87 and FaDu irradiated in vitro under plateau phase, aerobic conditions. The alpha/beta ratios obtained were 9.2 and 15.0 Gy, respectively. Such high alpha/beta values suggest a therapeutic gain could result from the use of small doses per fraction. PMID- 2318690 TI - Computerized tomography versus perfusion lung scanning in canine radiation lung injury. AB - Computerized tomographic (CT) measurements of lung density were obtained before and serially after thoracic irradiation in dogs to detect the alterations caused by radiation therapy. Fourteen mongrel dogs were given either 2000 cGy (Group A, 10 dogs, right lower zone irradiation), 1000 cGy (Group B, 2 dogs, right lower zone irradiation), or 500 cGy (Group C, 2 dogs, right lung irradiation) in one fraction. Once before and bi-weekly after irradiation, the anesthetized dogs had thoracic CT scans. CT numbers for the irradiated area were compared to their preirradiation control values. Macro-aggregated albumin (MAA) perfusion lung scans were also obtained before and at weekly intervals after irradiation and were evaluated visually and quantitatively for abnormalities. When both these tests were abnormal, or at the end of the scheduled study, the dogs were sacrificed to confirm radiation lung injury histologically. Our results showed that CT numbers (as a measure of tissue density) were higher with higher doses of radiation. Among all the techniques used, only the quantitative assessment of macro-aggregated albumin perfusion scan detected abnormalities in all the dogs given 2000 cGy. Their abnormalities correlated well with the presence of radiation lung damage histologically, however, the applicability of these methods in the detection of early injury has to be further evaluated. PMID- 2318691 TI - Radiosensitization of two murine fibrosarcomas with 6-thioguanine. AB - In Vivo murine tumor experiments were carried out to determine whether 6 thioguanine (6-TG) could enhance the cytotoxic effects of radiation on tumors. The combined effects of single and fractionated x-irradiation were evaluated on the transplanted methylcholanthrene induced fibrosarcoma (Meth-A) in BALB/c mice, a moderately radioresponsive tumor and on the radiation induced fibrosarcoma (RIF) in C3H/He mice, a highly radioresistant tumor. The combined treatment of single administration of 6-TG (25 mg/kg) and of x-irradiation (20 Gy) on Meth-A tumors produced more than 90% tumor control, whereas the radiation alone resulted in less than 5% tumor control. The radiosensitizing effect by 6-TG was higher when the drug was administered either 1 to 8 hr prior to or 24 hr after x irradiation. The dose modification factor of single dose 6-TG (10 mg/kg) is estimated to be 1.47 for Meth-A tumor and 1.25 for RIF tumor. The tumor control rates of fractionated irradiation alone and with concomitant 6-TG in Meth-A tumors were 14% and 59%, respectively. Based on the studies reported here and well documented pharmacokinetics in humans, it is suggested that combined radiation therapy and 6-TG may provide an enhanced therapeutic effect even in tumor varieties where the drug has no apparent anti-tumor activity on non irradiated cells. PMID- 2318692 TI - Pathophysiological changes after local heating of rat liver. AB - Changes in blood flow in rat liver by local heating of the left lateral lobe were studied. A small portion of the left lateral lobe was heated by capacitive application of 8 MHz RF with a 2 cm diameter electrode on the ventral surface and a 7 cm diameter electrode on the dorsal surface of upper body of rats. A circular area with diameter of about 1 cm in the left lateral lobe could be heated to relatively homogeneous temperatures. The temperature in the remaining part of the left lateral lobe as well as in the rest of liver tissue also increased to varying degrees during the local heating of the left lateral lobe. When heated at 39 degrees or 41 degrees C for 45 min, the arterial blood flow, as measured with the radioactive microsphere method, in the heated area, and that in the rest of the left lateral lobe as well as in the whole liver initially increased during the first 30 min and then started to decline. During a 45 min heating at 43 degrees C, the arterial blood flow in the heated area slightly increased for 15 min and then significantly decreased thereafter. The arterial blood flow in the rest of the liver tissue also increased during the first 15 min of a 43 degrees C heating and began to decline. Histological examination of liver heated at 43 degrees C for 30 min showed wedge-shaped infarctions early on, which appeared to be organized into scar tissue by 7 days after heating. The concentrations of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) in the serum significantly increased 2 hr after heating the small portion of the left lateral lobe at 43 degrees C for 30 min and began to decrease thereafter although the serum level of GOT and GPT was still greater than the control value 24 hr after heating. PMID- 2318693 TI - Thermal enhancement of radiation-induced leg contracture. AB - Early and late damage in the normal tissues of the legs of mice was compared following treatment with radiation alone or radiation followed immediately by hyperthermia. Hyperthermia was given by immersing the hind leg in a water bath at 43.0 degrees, 43.3 degrees, or 43.5 degrees C for 1 hr. Damage was assayed by measuring leg contracture at various intervals from 5 to 365 days after treatment. At 5 days after treatment, only hyperthermia-induced contracture was observed. At 10 and 20 days, contracture increased with radiation dose in heated legs, but little contracture had developed in mice treated with radiation alone. By 45 through 365 days, however, contracture correlated with radiation dose both in mice treated with radiation alone as well as in those treated with radiation and hyperthermia. The greatest differential in the slopes of the dose response curves, suggesting hyperthermic radiosensitization, was seen 20 days after treatment. Nevertheless, at 365 days, contracture was still significantly greater in the mice treated with radiation and hyperthermia (43.5 degrees bath) than in the irradiated controls. Thermal enhancement ratios (TERs) were calculated from LCD50 values (LCD50 = radiation dose that would give a stated level of leg contracture in 50% of the mice). For greater than or equal to 3 mm contracture, TERs were 4.1 to 7.9 at 30 days, depending on bath temperature, but only 1.1 to 1.5 at 365 days. For an isoeffect of greater than or equal to 7 mm contracture, TERs were 1.9 to 5.3 at 30 days, and 0.8 to 1.8 at 365 days. Thus, contracture was enhanced more at 20 to 30 days after treatment with radiation and hyperthermia than at 120 through 365 days. Radiation damage not only appeared earlier in mice treated with hyperthermia than in those treated with radiation alone, but after the highest temperature tested (43.5 degrees bath), contracture was greater from 5 through 365 days after treatment than in controls treated with radiation alone. PMID- 2318694 TI - Prevention of hypothyroidism related to mantle irradiation for Hodgkin's disease: preparative phantom study. AB - To decrease the incidence of hypothyroidism related to mantle irradiation for Hodgkin's disease, we initiated a study designed to protect the thyroid gland using a phantom. A thyroid phantom was filled with technetium-99m. The thyroid phantom was placed inside of its corresponding anterior neck position in a whole body phantom. An anterior scintiscan of the head and neck region demonstrated the radioactivity in the simulated thyroid. A mantle port included a focused block that would shield the thyroid from the anterior port. The phantom was exposed (4 MeV) to 180 cGy (AP-PA) at midplane with lithium fluoride dosimeters in the position of the thyroid. The thyroid received an average of 12 cGy from the anterior field and 48 cGy from the posterior field for a total of 60 cGy per treatment or 30% of the prescribed dose. A complete mantle field course of radiation of 4000 cGy would lead to a thyroid dose of 1200 cGy at a daily fractional dose of 60 cGy. We elected not to block the thyroid from the posterior field to prevent shielding and potential underdosage of involved nodal sites. The present study suggests a method of safe and effective thyroid shielding which needs to be tested clinically to determine whether it would reduce the incidence of chemical and clinical hypothyroidism or simply extend the period until occurrence. PMID- 2318695 TI - Tolerance of the liver to the effects of Yttrium-90 radiation. AB - There are no reliable data documenting the tolerance of the human liver to ionizing radiation from a continuous Yttrium-90 source. As Yttrium-90 incorporated into microspheres is being used to treat patients with liver cancer, it is imperative that the tolerance of the human liver to this form of radiation damage be determined. Four patients with metastatic liver cancer were treated with Yttrium-90 to deliver radiation doses above that considered tolerable when given by conventional external sources. Patients were monitored with serial estimations of liver function tests and between 7 and 9 months after treatment liver biopsies were performed. Histological examination of the liver biopsies confirmed only minimal changes in the normal liver parenchyma. These data indicate that the human liver may tolerate relatively large radiation doses when delivered by Yttrium-90 microspheres embedded in the liver parenchyma as a number of discrete point sources. PMID- 2318696 TI - Twice-daily anesthesia in infants receiving hyperfractionated irradiation. AB - Four children ranging in age from 6-30 months were treated with twice-daily (BID) radiation therapy under general anesthesia with a 5-6 hr treatment interval. Anesthesia was accomplished with sodium thiopental administered intravenously (IV) by bolus injection. This as followed by continuous drip infusion of sodium thiopental in a few instances where more prolonged anesthesia was required. Children received an initial formula feeding 6 hr before their first treatment and were subsequently kept NPO (nothing by mouth) until they recovered from their second anesthesia. Recovery from thiopental was rapid and children were ready for a normal feeding within 1-1 1/2 hr of the second treatment. No parenteral feedings were required in any of these patients. Children maintained their weight during courses of radiation therapy which ranged between 19 and 43 elapsed days. There were no radiation-related treatment breaks. One child experienced two hypotensive episodes during anesthesia which responded rapidly to intravenous atropine. No other anesthetic complications occurred. This experience demonstrates that hyperfractionated radiation therapy can be safely delivered in infants requiring general anesthesia for immobilization. We feel that sodium thiopental is the anesthetic of choice in this setting because of the short duration of action and consequently rapid post-anesthesia recovery which makes it possible to achieve adequate nutrition with oral feedings alone. PMID- 2318697 TI - The results of radiotherapy of cancer of the middle ear. AB - Between 1971-1986 29 patients with cancer of the middle ear were treated with radiotherapy. Eighteen patients were treated with curative intent, 17 after incomplete surgery and 1 after biopsy only. Eleven patients were irradiated palliatively. In curative radiotherapy wedge pair technique or mixed photon electron beam was used with a tumor dose of 60 Gy in 24-30 fractions. The probability of 5-year disease-free survival (DFS) is 53% for patients treated with curative intent. There is a correlation between extent of disease and survival. Excessive early reaction was observed in two patients, and late bone necrosis in one. Mean survival in the palliatively irradiated group was 3.6 months. PMID- 2318698 TI - A digital fluoroscopic imaging device for radiotherapy localization. AB - We have been developing a digital fluoroscopic imaging system to replace the portal films that are currently used to verify patient positioning during radiotherapy treatments. Our system has a number of modifications compared to previously reported devices. The detector, which consists of a copper plate with Gd2O2S:Tb phosphor bonded directly to the copper, has been designed to maximize light output from the phosphor by increasing the phosphor thickness. The operation of the T.V. camera has been modified so that the light signal is accumulated on the target of the T.V. camera for periods of 0.2-2.0 seconds. Accumulation of the light increases the video signal relative to the fixed noise current generated by the camera, and thus minimizes the camera noise. The resulting image quality is comparable to film, so the imaging system represents a promising alternative to film as a method of verifying patient positioning in radiotherapy. PMID- 2318699 TI - Computation of digitally reconstructed radiographs for use in radiotherapy treatment design. AB - The increasing use of 3-dimensional radiotherapy treatment design has created greater reliance on methods for computing images from CT data which correspond to the conventional simulation film. These images, known as computed or digitally reconstructed radiographs, serve as reference images for verification of computer designed treatments. Used with software that registers graphic overlays of target and anatomic structures, digitally reconstructed radiographs are also valuable tools for designing portal shape. We have developed radiograph reconstruction software that takes full advantage of the contrast and spatial detail inherent in the original CT data. This goal has been achieved by using a ray casting algorithm which explicitly takes into account every intersected voxel, and a heuristic approach for approximating the images that would result from purely photoelectric or Compton interactions. The software also offers utilities to superimpose outlines of anatomic structures, field edges, beam crosshairs, and linear scales on digitally reconstructed radiographs. The pixel size of the computed image can be controlled, and several methods of interslice interpolation are offered. The software is written in modular format in the C language, and can stand alone or interface with other treatment planning software. PMID- 2318700 TI - Development of total-skin electron therapy at two energies. AB - Total-Skin Electron Therapy (TSET) modalities have been developed at two energies on a Varian Clinac 1800. The physical criteria for the beams were determined mainly from the requirement of continuing the Stanford treatment technique, which was 12 Total-Skin Electron Therapy portals combined in six pairs. The penetration of the lower energy mode matches that previously obtained at Stanford on the Varian Clinac 10, (about 4 mm for the 80% isodose contour in the 12-field treatment). The penetration of the higher energy mode is about 8 mm at the 80% contour. The Total-Skin Electron Therapy modes necessarily use electrons produced by the two standard electron-beam modes of lowest energy, nominally 6 and 9 MeV. Measurements to verify the beam specifications were carried out with diodes, a variety of ionization chambers, and a specially constructed circular phantom for film dosimetry. Initially, the penetration of the Total-Skin Electron Therapy beams was too large to match our criteria, so two methods of reducing it were explored: (a) the energies of the electron beams produced by the machine were reduced (which also reduced the energies of the corresponding standard electron modes) and (b) a large polymethylmethacrylate degrader (2.4 m X 1.2 m) 1 cm thick was placed just in front of the patient plane. Acceptable Total-Skin Electron Therapy beams could be produced by either method and the latter was finally used. The use of the standard dose monitoring system for the Total-Skin Electron Therapy modes considerably simplifies the daily treatment delivery as well as the implementation. However, the need for reasonable dose rates at the treatment plane (3.5 meters beyond the isocenter) requires dose rates of 24 Gy/min at the isocenter. Nevertheless, it is possible to use the internal dose monitor provided the problems associated with high dose rates (recombination and amplifier saturation) are addressed. Solutions to these problems involved switching the primary and back-up dose monitors, increasing the collecting voltage on the ion chambers, and calibrating the dose monitor so that 1 unit = 1 cGy at the patient rather than at the isocenter. PMID- 2318701 TI - Analysis of movement of intrathoracic neoplasms using ultrafast computerized tomography. AB - Twenty patients with intrathoracic neoplasms were evaluated with ultrafast (cine) computerized tomography to determine the contribution of tumor motion to geographic errors. The treatment portals were setup with conventional simulation techniques and then scanned with cine computerized tomography. Eight tomographic levels were studied, 10 images per level over 7 seconds time. Major geographic misses were detected in three patients (15%), and minor geographic misses in an additional three (15%). The greatest tumor movement was noted in lesions located adjacent to the heart or aorta or near the diaphragm. Five of six hilar lesions showed significant lateral motion (average = 9.2 mm) with cardiac contraction, and three of four lower lobe lesions showed significant craniocaudal movement with respiration. Mediastinal lesions moved an average of 8.7 mm laterally. Lesions in the upper lobes showed minimal movement (average = 2.2 mm), and tumors attached to the chest wall showed no measurable movement. PMID- 2318702 TI - An interactive treatment planning system for ophthalmic plaque radiotherapy. AB - Brachytherapy using removable episcleral plaques containing sealed radioisotope sources is being studied as an alternative to enucleation in the treatment of choroidal melanoma and other tumors of the eye. Encouraging early results have been reported, but late complications which lead to loss of vision continue to be a problem. A randomized national study, the Collaborative Ocular Melanoma Study (COMS) is currently in progress to evaluate the procedure. The COMS specified isotope is 125I. Precise dosimetric calculations near the plaque may correlate strongly with complications and could also be used to optimize isotope loading patterns in the plaques. A microcomputer based treatment planning system has been developed for ophthalmic plaque brachytherapy. The program incorporates an interactive, 3-dimensional, solid-surface, color-graphic interface. The program currently supports 125I and 192Ir seeds which are treated as anisotropic line sources. Collimation effects related to plaque structure are accounted for, permitting detailed study of shielding effectiveness near the lip of a plaque. A dose distribution matrix may be calculated in any subregion of a transverse, sagittal, or coronal planar cross section of the eye, in any plane transecting the plaque and crossing the eye diametrically, or on a spherical surface within or surrounding the eye. Spherical surfaces may be displayed as 3-dimensional perspective projections or as funduscopic diagrams. Isodose contours are interpolated from the dose matrix. A pointer is also available to explicitly calculate and display dose at any location on the dosimetry surface. An interactive editing capability allows new plaque designs to be rapidly added to the system. PMID- 2318703 TI - The "recall effect" in radiotherapy: is subeffective, reparable damage involved? AB - It has been proposed that lethal mutations among the progeny of a surviving cell could be the basis for the recall effect when chemotherapy is applied subsequent to the repair of normal-tissue injury resulting from a course of radiation therapy. Because radiotherapy is usually multifractionated, the possibility exists that repair of heritable injury of this type could occur between fractions as is the case for sublethal damage. To examine this possibility, the endpoint small-colony formation was used--an endpoint which integrates the effects of a number of radiation-induced aberrancies including lethal mutations--and low-dose rate irradiation. It was found that, even after net surviving fractions comparable to those sought in radiotherapy were reached, little damage remained expressible as a deficiency in the size of the colony generated from a surviving cell. We conclude that the damage expressible as a lethal mutation is reparable and therefore the recall effect must be attributed to some other cellular mechanism. PMID- 2318704 TI - Regulation, coverage, and reimbursement of medical technologies. AB - Two major barriers to the introduction and diffusion of medical devices exist. First, devices must be cleared for marketing by The United States Food and Drug Administration, as mandated by the Medical Device Amendments of 1976. Second, third party payers are now making explicit determinations about whether or not to cover the specific applications of medical devices and about appropriate levels of reimbursement. This paper illustrates these processes which are based upon the evaluation of the safety and effectiveness of medical devices and examines the implications of the processes for the innovation and availability of such technology. PMID- 2318705 TI - On the definition of local control. PMID- 2318706 TI - Are cancer researchers speaking the same language? PMID- 2318707 TI - Preoperative irradiation in endometrial carcinoma: a reassessment? PMID- 2318708 TI - Low dose, continuous infusion 5-fluorouracil plus radiotherapy for anal cancer. PMID- 2318709 TI - Differential characteristics of adolescent pregnancy test patients: abortion, childbearing and negative test groups. AB - Studies of the consequences of adolescent childbearing report many negative sequelae, but the effects of induced abortion are less studied, and most studies lack appropriate controls for preexisting characteristics. This paper uses baseline data from the intake interview into a longitudinal study of 360 innercity black women (less than or equal to 17 years old) presenting for a pregnancy test at two sites in Baltimore to examine baseline differences between three groups: young women who terminated the index pregnancy and, as controls, those who carried to term and those whose tests were negative. They were interviewed before being told the test result. Education aspirations/achievement, economic well-being, sexual/contraceptive history, psychologic characteristics, and desire for a child were compared. Negative test patients often reveal characteristics suggesting a particularly high risk of pregnancy, e.g., more prior pregnancy tests and a greater desire to conceive. Implications are discussed, emphasizing the need to intervene after a negative pregnancy test with counseling to help avert a future undesired conception. PMID- 2318710 TI - Frequency of use, knowledge, and attitudes toward the contraceptive sponge among inner-city black and Hispanic adolescent females. AB - This study assessed the frequency of use, knowledge, and attitudes toward the contraceptive sponge in sexually active, inner-city, black and Hispanic adolescent females. A 54-item, self-administered questionnaire was completed by 208 adolescents (mean age 17.9 years) attending a gynecology/family planning clinic within a comprehensive adolescent health center. Twenty-nine (13.9%) had never used any birth control, and 49 (23.6%) had not used any form of birth control in the 3 months prior to the study. Fifty-three (25.5%) of the adolescents had used a less reliable method such as rhythm and/or withdrawal. The birth control method used least was the sponge. Only four (1.9%) of the adolescents had used the sponge in the 3 months prior to the study, and only ten (4.8%) had ever used it. Knowledge of the correct use of the sponge was poor. However, 69 (44.8%) of the 156 girls who knew about the sponge had a positive attitude toward it, and only 19% said they did not like it. The contraceptive sponge may be a viable option for adolescents, particularly those who are not using birth control or who are using a less reliable method. PMID- 2318711 TI - Do health care needs of indigent Mexican-American, black, and white adolescents differ? AB - Few studies have addressed the specific health care needs of Mexican-American adolescents. This 2-year study assessed the routine health care needs and incidence of chronic illness among 279 Mexican-American, 233 white, and 333 black indigent adolescents enrolled in a vocational training program. Mexican-Americans were more likely to have a positive purified protein derivative tuberculin test and acne/eczema requiring treatment. Blacks were more likely to have incomplete immunizations and thyroid disorders, while whites were more likely to have musculoskeletal conditions and require family planning services and psychiatric intervention for mental health disorders. Although no difference in incidence of chronic illness was noted, our data suggests that routine health care needs may differ among indigent Mexican-American, white, and black adolescents. PMID- 2318712 TI - Blunted growth hormone responses to clonidine in adolescent girls with early anorexia nervosa. Evidence for an early hypothalamic defect. AB - We studied growth hormone (GH) levels in 14 adolescents with anorexia nervosa (AN), 12-20 years of age. All had amenorrhea and the duration of symptoms ranged from 2-24 months. There was no difference in unstimulated GH between the girls with AN and endocrinologically normal girls. However, the GH response to the alpha-adrenergic agent clonidine was blunted (less than 10 ng/ml) in 11 of 14 girls with AN. Our results of a normal basal GH level and blunted response to stimulation is in contrast to some reports of high basal GH levels and an exaggerated response to pituitary stimulation although it agrees with other studies. Our patient population was younger and at an earlier stage of the disease (12 with symptoms for less than 1 year) than the AN patients previously reported to have elevated GH secretion. In view of studies that report an elevated GH response to growth hormone releasing factor, our results suggest that the AN patient's abnormalities in GH secretion may result from an abnormal hypothalamic response to adrenergic stimuli. This hypothalamic abnormality might also contribute to the growth failure seen in adolescent girls with AN. PMID- 2318713 TI - Adolescent medicine in pediatric practice. AB - Adolescents report important unmet health care needs. This study directly assesses pediatricians' current practices pertinent to the primary care of adolescents. An anonymous questionnaire survey of general pediatricians was conducted in two suburban counties in New York State. Of the 101 respondents, 51% were older than age 50 and 88% were in private practice. The "average" pediatrician saw 28 patients in a 7-hour office day. Approximately 1 in 10 regularly saw patients with a sexuality-related concern, substance abuse problem, or anorexia nervosa. Fewer than half provided anticipatory guidance regarding sexuality, and only 14% questioned teens about depression. Respondents perceived factors related to fees, lack of time, lack of knowledge, and their image as obstacles to an expanded care of adolescents. Those with some training in adolescent medicine during residency were significantly more likely to provide care and anticipatory guidance related to sexuality and substance abuse. Thirty percent reported an interest in increasing their involvement with adolescents. We conclude that most of these pediatricians played a small role in meeting the health needs of adolescents. PMID- 2318714 TI - Patient-controlled analgesia in adolescents. AB - Patient-controlled analgesia (PCA) is a method of administering narcotics in which the patient activates a machine to administer a small bolus of narcotic. In the first year of PCA use in our hospital, 26 patients used PCA. We suggest a dose volume of 0.015 mg/kg/dose and a 4-hour limit of 0.25 mg/kg/4 hr, with a lock-out of 10 minutes. Patients used approximately equivalent amounts to standard parenteral narcotics, but there was a wide interpatient variability in the amount of narcotic used. No clinical respiratory depression was noted, and patients did not titrate themselves to complete analgesia. PCA is an effective means of pain control in adolescent patients. PMID- 2318715 TI - Runaway and homeless youth in Los Angeles County, California. AB - Data collected over one year from agencies in Los Angeles County serving homeless youth suggest that shelter and outreach/drop-in agencies serve different populations. Shelters serve about equal numbers of males and females, almost half of whom are 15 years old or younger. Slightly more than half of these young people are minority youth who live in Los Angeles County. Seven of 10 go on to live in a stable environment. Outreach/drop-in agencies serve predominantly males, almost all of whom are 16 years old or older. These clients are primarily white and from outside Los Angeles. Four of 10 get off the streets. Both shelters and outreach/drop-in agencies serve primarily multiproblem chronic runaway or homeless youth who have neither families nor independent living skills and have survived as best they could. To help these young people, more emergency shelter beds and transitional living programs are needed. The geographic location and program structure of services however must be carefully considered. PMID- 2318716 TI - Toxic shock syndrome in three adolescent males. AB - Toxic shock syndrome (TSS) is associated with a spectrum of Staphylococcus aureus infections and is not just a disease of menstruating females. We report three cases of TSS in adolescent males. In one case the origin of infection was a cauterized wart that did not appear clinically infected. Two cases were associated with bacteremia and had demonstrable acute phase antibody to toxic shock syndrome toxin-1 (TSST-1). One of these patients died. The S. aureus strain from this patient did not produce TSST-1 but did produce enterotoxin D. The historical and clinical features of TSS are reviewed. PMID- 2318717 TI - Spontaneous pneumomediastinum in an adolescent patient. AB - Chest pain is a frequent complaint requiring evaluation. The differential diagnosis is extensive and includes diseases of the respiratory, cardiac, gastrointestinal, neurologic, or musculoskeletal systems. This report describes an adolescent patient with chest pain secondary to spontaneous pneumomediastinum. The work-up and etiology is discussed. PMID- 2318718 TI - Judgmentalism in the Society for Adolescent Medicine. PMID- 2318719 TI - G. Alan Stull's view of accreditation: a response. PMID- 2318720 TI - Predicting academic success in a nontraditional program. AB - Predictors and estimators of success in institutions of higher education have primarily been developed for traditional students in campus-based programs. With the rapidly increasing number of nontraditional allied health programs and students, there is a need to evaluate variables that may be used as predictors specifically for these students. This study examined the admission criteria and measures of success for 40 nontraditional respiratory care students. The subjects included 6 males and 34 females, who ranged from 17 to 50 years of age. The findings revealed a prediction model for three indicators of success: program average, clinical performance rating, and credentialing exam scores. Graduates' records were reviewed to assess which student selection criteria correlated well with these indicators. All models were significant at the 0.05 alpha level. These results may be useful in the selection of students for nontraditional respiratory care programs as well as in the selection of students for other allied health programs. PMID- 2318721 TI - Faculty research skills development. AB - This article presents a plan for faculty research skills development. Three categories of faculty research roles are described: researcher, researcher/teacher, teacher/research team member. A faculty member elects to be placed in one of the categories based on academic credentials, research expertise, and professional goals. At the departmental level, faculty share research ideas and receive mutual support through regularly scheduled biweekly faculty research meetings. Faculty research skills are cultivated via monthly seminars. Administrative support is furnished through a research management system designed to facilitate the process of initiating research projects and responding to external funding research opportunities in a timely manner. The research management component offers: seed money for pilot studies and small projects; funds for research assistants and consultants; focused information dissemination concerning funding sources; and clerical support systems for completing and submitting grant applications. PMID- 2318722 TI - Employee dependents: the future focus of worksite health promotion programs and the potential role of the allied health professional. AB - The prevalence of health promotion activities has increased in worksites over the last five years. Many companies that have offered health promotion programs in the past have done so primarily for their employees. In the last several years, programs have extended to employee dependents by opening current employee programs to dependents. However, employee health promotion programs may not be relevant or accessible to employee dependents, particularly when children or elderly parents are taken into consideration. This paper outlines several reasons for expanding health promotion benefits to include dependents, suggests a working construct for dependent programs, and discusses the possible roles of allied health professionals in these programs. PMID- 2318723 TI - General education in the professional curriculum: faculty perceptions of contributions. AB - This study investigated general education contributions to the professional development of majors in five selected health professional disciplines from 114 accredited programs. The findings identified that the most important general education contributions to health professional development, as perceived by faculty, included abilities to communicate verbally and in writing, to solve problems, to understand one's own and others' behavior, and to develop a personal value system. Although health professional faculty reported strong satisfaction with the size, content, and contribution of the general education curriculum, there was little collaborative curriculum planning between faculty in professional and general education programs. These latter findings are at odds with national reports lamenting the state of general education. A variety of strategies are described for opening channels of communication between health professional and general education faculty and for integrating general education and professional curricula. PMID- 2318724 TI - The 1989 Mary E. Switzer lecture: marketing health care services for the new millennium. PMID- 2318725 TI - The role of the academic coordinator of clinical education: a dilemma in academe. PMID- 2318726 TI - Intake and digestion of low-quality meadow hay by steers and performance of cows on native range when fed protein supplements containing various levels of corn. AB - Two trials were conducted to evaluate the effects of corn in protein supplements fed to cattle receiving low-quality forages. In Trial 1, four ruminally cannulated steers (avg BW 500 kg) and four intact steers (avg BW 270 kg) were used in a replicated latin square to determine intake and digestibility fo a low quality meadow hay (4.3% CP) when fed no supplement (NS), 1.12 g CP/kg BW (PS), 1.12 g CP/kg BW with corn supplying 1.98 g starch/kg BW (PLC) or 1.12 g CP/kg BW with corn supplying 3.96 g starch/kg BW (PHC). Hay DMI decreased (P = .001) and total diet DMI increased (P = .001) quadratically as supplemental corn increased. Diet DM digestibility increased (P = .004) and forage DM and hemicellulose digestibility decreased (P less than or equal to .018) quadratically as level of corn in the diet increased. In Trial 2, 135 cows received either ear corn (1.16 kg TDN and 127 g CP.hd(-1).d(-1), ear corn plus protein (1.16 kg TDN) and 290 g CP g CP.hd(-1).d(-1) or protein (.72 kg TDN and 290 g CP.hd(-1.d(-1) while grazing native Sandhills winter range for 112 d and while receiving hay (10% CP) during the following 60-d calving period. Cows that received ear corn lost (P less than .001) more weight than cows fed ear corn plus protein supplement, which lost more weight than cows fed only protein supplement (-54, -18 and 6 kg, respectively) during the 112-d winter grazing period. Cows that received ear corn and ear corn plus protein gained more (P less than .001) weight during calving and summer grazing (after supplement wa withdrawn) than protein-supplemented cows. Reproductive performance was not affected (P greater than .705) by treatments. PMID- 2318728 TI - Value of a molasses mixture containing natural protein as a supplement to brood cows offered low-quality forages. AB - In a 4-yr study, molasses (M; 6% CP), molasses-urea (MU; 17.5% CP; 92% molasses, 4% urea and 4% water) and molasses-cottonseed meal-urea (MCSM; 17.5% CP; 73% molasses, 25% cottonseed meal, 1% urea and 1% water) were compared as winter supplements for Braford cows (514 matings) consuming low-quality forage. Cows were fed 1.35, 1.50 and 1.27 kg.head-1.d-1 of the respective supplements for 127 d beginning in December. Cows were wintered on bahiagrass pasture (avg 8% CP) and stargrass hay (avg 5% CP). Quantity of hay offered averaged 7.6 kg.cow-1.d-1 over 109 d. Cows were exposed to bulls for 90 d beginning on March 1. Supplementation treatment did not affect cow live weight, live weight change or condition score (P greater than .05). However, pregnancy rate was higher (P less than .05) for cows fed MCSM (79.0%) than for cows fed M (67.8%). The pregnancy rate of cows fed MU (76.3%) was intermediate to, but not different (P greater than .05) from, that of cows fed either M or MCSM. Supplementation treatment did not affect calf performance as measured by birth weight, survival rate or weaning weight (P greater than .05). However, calves from cows fed MCSM were 6 d older (P less than .05) at weaning than calves from cows fed M. For 3-yr-old cows, pregnancy rate was considerably higher (P less than .05) for cows fed MCSM (69.6%) than for cows fed M (37.5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318727 TI - Effect of marketing treatments and transportation on feeder pig performance. AB - During four 6-wk trials, 376 university-raised, crossbred feeder pigs were used to determine the effects of fasting (no feed or water) vs providing feed plus water or water alone at the simulated market and a 563-km transport on shrinkage and subsequent health and performance. Providing feed and water or water alone during a 12-h market simulation for Trials 1, 2 and 4 or a 24-h period for Trial 3 did not affect subsequent rate of gain (ADG) or feed efficiency (F/G) compared with pigs fasted during the market stay. However, overall shrinkage (market phase plus transportation) of pigs provided feed and water at the market was less (P less than .05) than for fasted pigs (4.0 vs 8.4% for Trials 1, 2 and 4; 4.5 vs 11.8% for Trial 3). Transporting the fasted or nonfasted feeder pig 563 k did not affect subsequent health or performance. Overall shrinkage of the fasted pigs that were transported 563 km vs those that were not transported during Trial 4 was not different (8.8 vs 9.1%; P greater than .05). In conclusion, one-owner feeder pigs can cope with the stress of fasting and transporting long distances without any extended detrimental effects on subsequent health and performance. PMID- 2318729 TI - Biological type effects on gestation length, calving traits and calf growth rate. AB - Gestation length, birth weight calving difficulty, calf mortality rate at birth, calf mortality rate from birth to weaning, preweaning calf growth rate and calf 200-d weight were evaluated in a biological type study in which four sire breeds were bred by AI to Hereford dams. Angus and Red Poll sires represented breeds of medium size, and Pinzgauer and Simmental sires represented large breeds. Angus and Pinzgauer represented breeds with medium milk production, and Red Poll and Simmental represented breeds with high milk production. Dams mated to large sire breeds had longer (P less than .01) gestation lengths (.95 d) and higher calving difficulty scores than dams mated to medium-sized sire breeds. Calves from large sire breeds had heavier birth weight (P less than .01) and 200-d wt (6.1 kg; P less than .01) than calves from medium-sized sire breeds. Calf death loss and ADG to weaning were similar (P greater than .10) for all breeds of sire. Calves from the higher milk level sire breeds exceeded the medium-milk breeds in birth weight (1.3 kg; P less than .01) but did not (P greater than .10) in other traits. Calves from the higher milk level sire breeds exceeded the medium-milk breeds in birth weight (1.3 kg; P less than .01) but not (P greater than .10) in other traits. Interaction between size and milk production of sire breed existed for gestation length, birth weight, ADG from birth to weaning and 200-d calf weight (P less than .01). In general, mature size of sire breed was a good indication of expected performance traits not easily influenced by environment. Not all differences, however, could be explained by size and milk production of the size breed. PMID- 2318730 TI - Dose response in growth of pigs injected daily with porcine somatotropin from 57 to 103 kilograms. AB - Exogenous administration of porcine somatotropin (PST) has been shown to promote growth in the pig; however, dose-response relationships and interactions with PST source and sex for animals taken to market weight have not been established clearly. The present study was conducted to determine the relationship between dosage of pituitary-derived and recombinantly manufactured PST (pPST and rPST) and growth (ADG), structural soundness, gain-to-feed ratio (G/F) and average daily feed intake (ADF). Crossbred barrows (n = 113) and gilts (n = 97) were injected with either saline, 1.5, 3.0, 6.0 or 9.0 mg/d of pPST or rPST from 57 +/ .3 to 103.5 +/- .7 kg live weight. Pigs were housed five per pen and had ad libitum access to an 18% crude protein diet for the duration of the experiment. Response curves for pPST and rPST did not differ (P greater than .20) for ADG, soundness score or ADF. Although regression coefficients for response of G/F to pPST and rPST differed (P = .05), pairwise comparisons of treatment means did not (P greater than .10). Response curves for barrows and gilts did not differ for ADG or soundness (P greater than .05). Averaged over PST source and sex, quadratic dose-responses were detected for ADG, G/F and ADF (P less than .01), but PST had no effect on soundness (P greater than .25). Exponential regression models best described the dose-response relationships, and 6.0 mg.pig-1.d-1 was predicted to result in 95% of maximal achievable response for days to 103.5 kg and G/F. At this dose, pigs were predicted to grow .15 kg/d (20%) faster during the treatment period, reach slaughter weight 11.6 d earlier, consume .56 kg/d (19%) less feed, and have a G/F .095 (36%) greater than controls. PMID- 2318732 TI - Zinc bioavailability in feed-grade sources of zinc. AB - Chick bioassays were used to assess bioavailability of zinc (Zn) from inorganic Zn sources. A soy isolate-dextrose diet containing 13 mg Zn/kg diet was supplemented with feed-grade sources of ZnSO4.H2O (ZnSO4) or ZnO and fed for 2 wk after a 7-d Zn-depletion protest period. Bioavailability of Zn in ZnO relative to ZnSO4 (set at 100%) was determined by multiple regression slope-ratio methodology, using both growth and tibia Zn accumulation in chicks fed graded levels of ZnO and ZnSO4. Linear responses for gain and tibia Zn occurred at dietary Zn levels (ZnSO4.7H2O) between 13 mg/kg (basal) and 33 mg/kg (gain) or 53 mg/kg (total tibia Zn). Therefore, two bioavailability assays were conducted using supplemental Zn levels of 0, 7.5 and 15 mg/kg from each Zn source. When weight gain was regressed on supplemental Zn intake, bioavailability of Zn in ZnO was only 61.2% (P less than .01) that of ZnSO4. When total tibia Zn was regressed on supplemental Zn intake, bioavailability of Zn compared with ZnSO4 (set at 100.0%) was 44.1% (P less than .001) for ZnO. With chicks fed soy-based diets, bioavailability of Zn from ZnO was less than that of ZnSO4. PMID- 2318731 TI - The effect of an adaptation period to soybean oil additions in the diets of young pigs. AB - Utilization of soybean oil (SBO) in swine starter diets and the effect of an adaptation period to SBO on performance was studied in two 4-wk experiments with pigs initially 4 to 5 wk of age. One trial was extended an additional 4 wk and apparent DE was measured during the 4th wk postweaning. Corn-soybean meal-based diets were used in which SBO was substituted for cornstarch at 2, 4 and 6% of the diet in Exp. 1 and at 3 and 6% of the diet in Exp. 2. In Exp. 2, SBO was added either initially (adaptation) or after 2 wk (no adaptation). In Exp. 1 daily gain and efficiency of feed utilization were improved (P less than .05) by adding SBO during wk 3 and 4, but not earlier. Feed intake was not affected by treatment. In Exp. 2, for the initial 4-wk postweaning period, there was no effect of SBO addition on growth rate; feed intake was depressed (P less than .05) when SBO was added at wk 3, and efficiency of feed utilization was improved (P less than .05) for pigs fed SBO without an adaptation period. The primary improvements in performance occurred in the 3rd and 4th wk postweaning, with a tendency for pigs to perform better without an adaptation period. During wk 4, pigs adapted to SBO consumed more (P less than .05) feed but tended to be less efficient (P less than .10) than nonadapted pigs. With or without adaptation, apparent DE was unaffected by SBO additions. Regardless of adaptation period, SBO additions depressed feed intake (P less than .05) and improved efficiency of feed utilization (P less than .01) for the 5- to 8-wk growing phase. In conclusion, adding SBO the first 2 wk postweaning did not improve performance; an adaptation period was not necessary for a performance response from added SBO. PMID- 2318733 TI - The influence of ovariectomy on luteinizing hormone concentrations in anestrous and cyclic sows. AB - In an effort to determine whether anestrus in swine is due to aberrant ovarian feedback control of gonadotropin release, this study contrasted the influence of ovariectomy on LH concentrations in serum of anestrous sows and in sows that returned to estrus following weaning. Blood samples were collected at 6-h intervals from 7 d prior to until 4 d after ovariectomy of 22 anestrous and 24 cyclic sows. Blood samples also were collected at 15-min intervals for 8 h at 2 d prior to and 2 d after ovariectomy. Sampling at 6-h intervals continued until 12 d after ovariectomy and additional 8-h windows of 15-min samples were taken at 7 and 12 d after ovariectomy of seven anestrous and nine diestrous sows. Mean LH concentrations and LH pulse frequencies were greater (P less than .05) 2 d after ovariectomy than 2 d prior to ovariectomy in both anestrous and diestrous sows. Mean pulse amplitude had increased by 2 d after ovariectomy in anestrous sows but did not change in cyclic sows. Baselines as determined from the mean of all LH measurements excluding pulses, remained the same in both anestrous and diestrous sows at 2 d after ovariectomy. Pulse frequency, pulse amplitude, and mean LH concentration were greater (P less than .05) in both anestrous and diestrous sows at 7 and 12 d after ovariectomy than at 2 d prior to and 2 d after ovariectomy. Pulse amplitude on d 7 and 12 after ovariectomy decreased (P less than .05) in both anestrous and diestrous sows relative to those observed at earlier times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318734 TI - Replication requirements and number of ejaculates needed for assessing treatment effects on sperm output and seminal characteristics of electroejaculated Holstein bulls. AB - Two ejaculates were harvested by electroejaculation on each of 3 d per week for 14 wk from 14, 12- to 24-mo-old Holstein bulls. Ejaculates during the first 2 wk served to stabilize sperm output. Data for the remaining ejaculates were used in a components of variance approach to determine the number of bulls per treatment and ejaculates per bull that would be needed to provide adequate sensitivity and precision for assessing treatment effects on seminal characteristics. The latter included the number of sperm (total and motile), volume and sperm concentrations of the sperm-rich fraction, and the percentage of progressively motile sperm in first and second ejaculates or per day. Replication requirements declined as the number of ejaculates per bull was increased to about 15 to 25 but declined minimally thereafter. The number of bulls needed per treatment varied in relation to the size of the treatment response to be detected but was much greater than the replication used in typical experiments. Replication for assessing sperm output in first ejaculates or per day was approximately one-half as great for experiments in which pretreatment information was used to adjust post-treatment data. Tables should be useful as a guide for designing efficient, cost-effective studies of known sensitivity and precision. PMID- 2318735 TI - Number of mature follicles ovulating after a challenge of human chorionic gonadotropin in different breeds of sheep at different physiological stages. AB - The ovulatory response of ewes from breeds that differ widely in prolificacy (Ile de-France, ++ Booroola Merino, Romanov, F+ Booroola Merino and F+ Booroola Romanov with adult ovulation rates of about 1.5, 1.2, 3, 3 and 3.5 respectively) to 750 IU of hCG given at different physiological stages (before puberty, during anestrus or during the luteal phase) was compared. In all except one experiment, hCG induced ovulation in 73 to 98% of the lambs, indicating that follicles sensitive to LH were present at all stages studied. Ranking of the breeds according to hCG-induced ovulation rate in prepuberal lambs was similar to that based on adult ovulation rate. Furthermore, hCG induced more ovulations in prepuberal F+ than in ++ lambs (3.7 +/- 1.4 vs 1.7 +/- .8 at 4.5 mo of age) as well as in anestrous ewes (F + at 3.1 +/- 1.8 vs ++ at 1.6 +/- .7). Within ewes, the correlation between hCG-induced ovulation rate and mature ovulation rate was positive in nonprolific breeds but not significant in prolific breeds. We conclude that 1) the number of hCG-induced ovulations can be used to identify sheep that are carriers of the Booroola gene and 2) the mechanisms responsible for a number of large ovulatory follicles typical of a breed are present at stages (prepuberal, anestrus, luteal phase) other than the follicular phase. PMID- 2318736 TI - Effect of season and location on semen quality and serum concentrations of luteinizing hormone and testosterone in Brahman and Hereford bulls. AB - Hereford bulls from Montana (MH; n = 15) and Nebraska (NH; n = 15) and Brahman bulls from Texas (BB; n = 18) were relocated to one of three locations (LOC): Montana (MT), Nebraska (NE) or Texas (TX). All bulls were pubertal at the time of relocation in late May 1984. Semen was collected by electroejaculation within 1 wk after relocation and at 90-d intervals beginning in November 1984 through early February 1986. Bulls were given a GnRH challenge (200 micrograms i.m.) during the same week of semen collections. Bulls also were bled for 8 h at 20-min intervals in the fall of 1984 and the spring and fall of 1985 to determine endogenous concentrations of LH and testosterone. Season affected sperm concentration in all breeds (P less than .05) with decreases during the winter in BB and during the summer in NH and MH bulls. Brahman bulls had lower percentage of live cells (LIVE) than NH and MH bulls did (P less than .0001). Brahman bulls decreased in LIVE during the winter (P less than .001). Area under the LH curve after GnRH was lower (P less than .005) in BB than in MH and NH. Brahman bulls in MT had greater (P less than .02) area under the LH curve and lower (P less than .06) area under the testosterone curve than did BB in TX or NE during the winter. There was no seasonal fluctuation in LH or testosterone response to GnRH in NH or MH bulls at any LOC. Area under the endogenous LH curve was lowest (P less than .04) in BB. Basal endogenous testosterone concentration was greater (P less than .03) in NH than in MH or BB. Area under the endogenous testosterone curve was lower (P less than .03) in MH than in NH or BB. These results indicate that BB exhibit seasonal fluctuations in semen quality. This was not so apparent in semen quality traits of Hereford bulls. There also was a seasonal influence in BB on both endogenous testosterone and GnRH-stimulated LH and testosterone concentrations. Compared with Hereford bulls, Brahman bulls had lower endogenous and GnRH-stimulated concentrations of LH. PMID- 2318737 TI - The effect of abomasal methionine supplementation on nitrogen retention of growing steers postruminally infused with casein or nonsulfur-containing amino acids. AB - An experiment was conducted to develop a system useful for measuring methionine requirements of growing steers. Seven ruminally cannulated steers (312 kg, gaining .91 kg/d) were fed a diet based on ammoniated corn cobs, corn starch, molasses and urea. Quantities of N and sulfur-containing amino acids disappearing from the small intestine were 96.0 and 14.8 g/d, respectively. Postruminal infusions of Na-caseinate (CAS) resulted in linear (P less than .01) increases in N retention with values increasing from 30.1 g/d with no postruminal CAS infusion to 39.3, 50.8 and 59.2 g/d (averaged across methionine supplementation) when 100, 200 and 300 g/d CAS were infused. Postruminal infusions of a mixture of crystalline L-amino acids (simulating the nonsulfur-containing essential amino acid pattern of casein; SIM) at levels of 100, 200 and 300 g/d also led to linear increases (P less than .01) in N retention with steers retaining 30.9, 38.9 and 50.5 g N/d (averaged across methionine supplementation), respectively. Postruminal infusion of 12 g/d L-methionine across CAS and SIM infusions improved (P less than .01) N retention by 7.6 g/d but infusion of SIM, which is devoid of sulfur amino acids, also increased N retention. Responses to methionine supplementation was greatest when 200 or 300 g/d SIM were abomasally infused. The data are interpreted to demonstrate that, for steers fed a diet containing little true protein, postruminal supplementation with nonsulfur-containing amino acids tended to increase the ability of growing steers to respond to methionine supplementation. PMID- 2318738 TI - Influence of flake density on the comparative feeding value of steam-flaked corn for feedlot cattle. AB - Two trials were conducted to examine the influence of flake density (FD) on the feeding value of steam-flaked corn. Treatments consisted of corn that had been steam-flaked to mean densities of .42, .36 and .30 kg/liter (28, 24 and 20 lb/bu). In Trial 1, treatment effects on characteristics of digestion were evaluated using three crossbred steers with cannulas in the rumen and proximal duodenum. In Trial 2, treatment effects on feedlot performance were evaluated in a 112-d finishing trial involving 72 crossbred steers with an average initial weight of 312 kg. Flake density was directly related to flake thickness (P less than .01) and inversely related (P less than .01) to in vitro enzymatic digestibility of starch. Decreasing the FD resulted in a linear decrease (P less than .01) in ruminal pH and linear increases (P less than .05) in postruminal and total tract digestibility of starch. Postruminal digestibility of N and total tract digestibility of OM, N and energy also increased linearly (P less than .05) with decreasing FD. Flake density did not influence (P greater than .10) feedlot performance or carcass merit. There was a tendency (P greater than .10) for depressed rate and efficiency of gain for steers fed the 30 kg/liter FD corn. Improvements in digestibility and N utilization of SF corn-based diets as a result of decreasing FD from .42 to .30 kg/liter did not enhance feedlot performance. This may be due to digestive dysfunction, perhaps related to processing effects on ruminal pH. PMID- 2318739 TI - Influence of steaming time on site of digestion of flaked corn in steers. AB - Four crossbred steers (395 kg) with cannulas in the rumen, proximal duodenum and distal ileum were used to evaluate effects of steaming time of corn on characteristics of digestion. The basal diet contained (DM basis) 12% forage-and 75% corn. The corn portion of the diet was provided as either dry-rolled (DR) or steam-flaked (SF), which had been exposed to steam for 34, 47 or 67 min prior to flaking to a mean density of .34 kg/liter. Longer steaming times linearly increased in vitro reactivity of corn starch to amyloglucosidase. Steaming time had a quadratic effect (P less than .05) on ruminal starch digestion. Ruminal starch digestibility of corn steamed for 47 min was 7% less than for corn steamed for 34 or 67 min. Longer steaming time linearly increased (P less than .05) flow of non-ammonia N to the small intestine with the principal increase (5.4%) between 34 and 47 min steaming time. Steaming time did not influence (P greater than .10) small intestinal or total tract digestibility of OM, starch or N. Compared with DR, SF increased (P less than .01) ruminal, small intestinal and total tract digestibility of starch 21.9, 75.1 and 9.2%, respectively. Although SF resulted in marked improvements in digestibility over DR, steaming times greater than 34 min were not beneficial. PMID- 2318740 TI - Plasma and tissue vitamin E concentrations in sheep after administration of a single intraperitoneal dose of dl-alpha-tocopherol. AB - Blood plasma and tissue Vitamin E concentrations were determined in 20 sheep following a single i.p. dose of 5 g of dl-alpha-tocopherol. In addition, five sheep were used as controls (no treatment and killed at d 0). From the 20 vitamin E-dosed sheep, 4 were slaughtered on d 3, 6, 10, 15 and 28 after dosing. There was a significant time effect in alpha-tocopherol concentrations in all tissues. In most tissues, the peak alpha-tocopherol concentration was at 3 d postdosing. Uptake varied among the different tissues examined. Three days postdosing, a large uptake of vitamin E by the liver was observed; this supports the concept that hepatic tissues are a target organ for vitamin E action. Also at 3 d uptake was pronounced in spleen and lung. Vitamin E concentrations in the other body tissues at d 3 postdosing increased considerably, but to a lesser degree than those in liver, spleen and lung. Vitamin E concentration in all tissues declined 3 d after i.p. dosing. PMID- 2318741 TI - Predicting growth and performance of Holstein steers. AB - Refinements and additions were made to the growing cattle portion of the model of Fox et al. (1988) for predicting growth of Holstein steers. Based on observations of animal weight, DM intake (DMI), ADG, feed per gain (FPG) and diet ME, the modified model was tested on a database that included 299 feeding periods with Holstein steers fed in research trials over a period of 15 yr at Cornell University, the University of Minnesota and the University of Wisconsin. The modified model accounted for 93, 56 and 68% of the variation in DM intake, daily gain and feed required per unit gain, respectively. Averaged over all 299 periods in the database, the error in predicting DM intake, daily gain and feed required per unit gain was 1%, 4% and 2%, respectively. Analysis of residuals indicated that ME level did not influence the difference between predicted and observed values for DMI, ADG and FPG. Residuals analysis indicated that BW did not influence the difference between predicted and observed values for ADG and FPG but DMI of heavier cattle was overpredicted (P less than .01). These results indicated that the 8% increase in DMI for cattle over 318 kg was not warranted for the Holstein steers in this database, which were predominantly less than 15 mo at slaughter. The results of the validation indicate that this model accurately predicted performance of Holstein steers. PMID- 2318742 TI - The benefits of animal identification for food safety. AB - The Center for Veterinary Medicine supports the effort to have a practical, workable form of mandatory animal identification. An animal identification system will make tracing of the source of animals with drug or chemical residues quicker and more effective. One of the best means of addressing and solving the problem of residues is through mandatory livestock identification. A successful traceback benefits both the producer and the industry. The U.S. Department of Agriculture (USDA) has proposed a mandatory nationwide system to require that all swine in interstate commerce be identified. Under the proposal several means of identification are listed and could be used. Additional methods or devices could be requested in writing to USDA. Persons required to keep records under the system would maintain the documents at their place of business for 2 yr. Records would be available to authorized USDA employees during ordinary business hours. FDA has had difficulty tracing tissue residue violations, particularly those involving sulfamethazine residues in swine. Investigations involving culled dairy cows and veal calves also have been closed due to lack of producer identification. The ability for FDA to determine the source of residues is vitally important in a coordinated government program to eliminate illegal tissue residues. PMID- 2318743 TI - Changes in bacterial populations during red tides caused by Mesodinium rubrum and Gymnodinium catenatum in North West Coast of Spain. AB - Heterotrophic bacterial communities associated with four red tides caused by Mesodinium rubrum and Gymnodinium catenatum in two Galician Rias (North West Spain) were examined. Three of these were produced by the Mesodinium rubrum and the causative organism of a toxic bloom was Gymnodinium catenatum. In early stages of all the blooms, the diversity decreased but the total marine bacterial counts increased by one or two logs. Vibrio numbers were also incremented by two logs in two blooms of M. rubrum, while in the other bloom of this organism and in the red tide caused by G. catenatum a decrease in number of these bacteria was observed. A total of 116 bacterial strains were identified at the genus level and grouped into 12 phena. During the decomposition processes of two blooms of M. rubrum a zooplanktonic-type bacterial succession was observed (Vibrio, pseudomonads and Moraxella-Acinetobacter). On the other hand, during decomposition of the other red tide of M. rubrum and the bloom of G. catenatum, a typical phytoplanktonic-type succession occurred, as Pseudomonas and Moraxella groups became dominant for all the process. These results support the conflicting taxonomical position of M. rubrum. After the blooms, the changes in the community point towards the restablishment of the normal bacterial flora of the estuary (increase in diversity and decreases of bacterial numbers). Only the Vibrio strains, isolated from the non-toxic first and second red tides, displayed cytotoxic activities. A relationship among bacterial cytotoxicity and toxic effects of blooms cannot therefore be established. PMID- 2318744 TI - The incidence of Listeria spp. in soft cheeses, butter and raw milk in the province of Bologna. AB - Samples of soft cheese, butter and raw milk were examined for Listeria species. Listeria monocytogenes (serotype 1, haemolytic and virulent for mice) and L. innocua (the only other Listeria sp. isolated) were each found in 2/21 (1.6%) of soft cheese samples. Five per cent of butter samples were contaminated with L. innocua. No Listeria spp. were detected in 40 raw milk samples. The results were compared with similar studies in Italy and abroad. PMID- 2318745 TI - Inhibition of Candida adhesion to buccal epithelial cells by an aqueous extract of Allium sativum (garlic). AB - The effect of pre-incubation of either Candida or buccal epithelial cells (BEC) with different concentrations of aqueous garlic extract (AGE) was investigated, as well as the effect of mouth rinse with AGE on the adhesion of yeast to BEC. Adhesion of Candida spp. to BEC was significantly reduced after both short and long time exposure of yeast to AGE. A similar inhibition of adherence was observed upon preincubation of BEC with AGE. The adherence-inhibition activity of AGE treatment was antagonized by thiols such as L-cysteine, glutathione and 2 mercaptoethanol. In addition, germ-tube formation was suppressed when C. albicans cells were pretreated with AGE. There was a significant reduction in the adherence of yeasts to BEC collected immediately or 15 min after an oral rinse with AGE. No statistical significance in the adhesion of BEC collected 30 min after oral rinse with AGE and control BEC was observed. The diminished adherence of C. albicans to BEC after exposure to various concentrations of garlic may have clinical relevance. PMID- 2318746 TI - Effect of different carbohydrates on growth, polysaccharidase and glycosidase production by Bacteroides ovatus, in batch and continuous culture. AB - Bacteroides ovatus was grown in batch culture on 12 different carbon sources (five polysaccharides, seven monosaccharides and disaccharides). Specific growth rates were determined for each substrate together with polysaccharidase and glycosidase activities. Growth rates on polymerized carbohydrates were as fast or faster than on corresponding simple sugars, demonstrating that the rate of polysaccharide depolymerization was not a factor limiting growth. Bacteroides ovatus synthesized a large range of polymer-degrading enzymes. These polysaccharidases and glycosidases were generally repressed during growth on simple sugars, but arabinose was required for optimal production of alpha arabinofuranosidase. Polysaccharidase and glycosidase activities were measured in continuous cultures grown with either xylan or guar gum under putative carbon limitation. With the exception of beta-xylosidase, activities of the polymer degrading enzymes were inversely related to growth rate. This correlated with polysaccharide utilization which was greatest at low dilution rates. These results show that Bact. ovatus is highly adapted for growth on polymerized carbohydrate in the human colon and confirm that the utilization of polysaccharides is partly regulated at the level of enzyme synthesis. PMID- 2318747 TI - Differential response to benzylpenicillin in vivo of tolerant and non-tolerant variants of Streptococcus sanguis II. AB - A variant that was highly tolerant to benzylpenicillin was obtained from a non tolerant clinical isolate of Streptococcus sanguis II by repeated exposure to penicillin. The rabbit model of endocarditis was used to investigate the efficacy of a high dose regimen of benzylpenicillin (250 mg/kg; peak serum concentration c. 25 mg/l) in the prophylaxis and treatment of endocarditis during challenge or infection with the non-tolerant parent strain or its tolerant variant. The two strains exhibited a similar capacity to initiate infection. A single dose of penicillin administered 0.5 h before bacterial challenge protected six of nine rabbits infected with the non-tolerant parent strain, but none of nine infected with the tolerant variant. Treatment of established infection with penicillin administered twice daily for four days cured eight of 13 (61%) rabbits infected with the non-tolerant parent strain, but only one of 14 (7%) rabbits infected with the tolerant variant. These results support the view that tolerance to penicillin has therapeutic implications. PMID- 2318748 TI - The disposition and urinary metabolism of 14C-labelled FCE 22891, a pro-drug of FCE 22101, in animals. AB - [2-14C]FCE 22891 was given orally and intravenously to the rat, orally to the dog and monkey. Radioactivity was eliminated by both the renal and faecal route after oral administration, but mainly in the urine after the iv route in the rat. Radioactivity as expired 14CO2 was detected in the rat and accounted for less than 1% of the dose after iv and 3.2% after oral dosage within 72 h. After oral FCE 22891 labelled by 14C in the acetoxymethyl moiety, radioactivity recovered as expired 14CO2 accounted for over 55% of the dose at 72 h in the rat. No FCE 22891 was detected in plasma, whereas consistent amounts of FCE 22101 were detected. The metabolism was studied by radio-HPLC in the urine of the animals treated with [2-14C]FCE 22891. No unchanged drug was detected at any time interval. FCE 22101 was the main urinary metabolite with the exception of the dog and accounted for about one-half of the radioactivity excreted in 0-24 h urine. Significant amounts of metabolite P1, an open beta-lactam ring derivative obtained by action of dehydropeptidase, were found in the urine of rat and monkey but not in the dog. The remaining urinary radioactivity was due to other metabolites, named P, X and LP, which might originate from P1, as stability of P1 is pH-dependent. PMID- 2318749 TI - Pharmacokinetics of once daily intra-peritoneal aztreonam and vancomycin in the treatment of CAPD peritonitis. AB - The pharmacokinetics of aztreonam and vancomycin were studied in six adult patients who developed peritonitis during Continuous Ambulatory Peritoneal Dialysis. Aztreonam 3 g was added to the first exchange in each 24 h period with vancomycin 500 mg on the first day and 250 mg on each subsequent day (provided the pre-dose serum vancomycin concentration was less than 10 mg/l) for a total of ten days. Aztreonam and vancomycin concentrations were measured in the serum and dialysate at 1, 2, 6, 12, 18 and 24 h after the initial dose and pre-dose on days 5 and 10. By the end of the ten day study all patients had recovered clinically and had a normal dialysate. For aztreonam, the mean peak serum concentration was 84.3 mg/l (range 59.6-102.8), the mean 24 h pre-dose serum concentration was 23.0 mg/l (range 8.6-39.2) and the mean 24 h pre-dose dialysate concentration was 15.5 mg/l (range 5.0-32.0). For vancomycin, the mean peak serum concentration was 10.2 mg/l (range 8.1-12.6), the mean 24 h pre-dose concentration was 5.5 mg/l (range 3.6-6.4), and the mean 24 h pre-dose dialysate concentration was 3.4 mg/l (range 2.4-4.6). In the treatment of CAPD peritonitis, once daily intra-peritoneal administration of aztreonam 3 g with vancomycin 500 mg initially and 250 mg on subsequent days (serum concentrations permitting) provides concentrations of antibiotic in both the serum and dialysate throughout the 24 h period in excess of the inhibitory concentrations of those organisms most frequently encountered in this condition. PMID- 2318750 TI - Predictive value of susceptibility tests for the outcome of antibacterial therapy. AB - A total of 510 charts of patients who received antibacterial agents were examined for clinical outcome and microbiology findings. A total of 382 patients (75%) had one or more specimens submitted for culture and susceptibility tests before the administration of the drugs; 298 (78%) of these had positive cultures and susceptibility tests were done. A total of 18 species were isolated. Of the 298 patients with organisms of known susceptibilities, 271 (91%) received antibacterial agents to which the respective organisms were susceptible and 219 of these patients (81%) improved (P less than 0.05). This high rate of good infectious diseases practice is probably due to two factors: (1) susceptibility tests results were available in most cases the next day after the submission of a specimen; (2) the medical board distributed guidelines for the use of antibiotics and monitored the compliance closely. The patients treated with antibacterial agents to which the bacteria were resistant improved in 3% and did not improve in 82% (P less than 0.05) of the patients. This study shows that choosing an antibacterial agent in accordance to the susceptibility test resulted in a high rate of improvement. When the choice of agent disregarded bacterial resistance in vitro, therapy almost always ended in failure. Therefore, susceptibility tests in vitro have a good predictive value for the outcome of antibacterial therapy. PMID- 2318751 TI - Uptake of cephalosporins by human intestinal brush-border membrane vesicles. PMID- 2318752 TI - Possible interaction of ciprofloxacin with ferrous sulphate. PMID- 2318753 TI - The effect of sub-inhibitory concentrations of chlorhexidine on the proteolytic activity of Bacteroides gingivalis. AB - Bacteroides gingivalis was grown in the presence of chlorhexidine at concentrations lower than the minimum inhibitory concentration (1.25 mg/l). These sub-inhibitory concentrations were found to stimulate growth in terms of an increase in the number of viable cells, the greatest increase being at a concentration of 0.75 mg/l of chlorhexidine. The total proteolytic activity of the cultures (assayed by means of azocasein hydrolysis) grown in the presence of chlorhexidine and their specific activities (per 10(6) cells) were found to be less than those of the cultures grown in the absence of chlorhexidine. In the case of the trypsin-like activity of the microorganism, a different pattern was found. Thus, although the specific activities of the chlorhexidine-grown cultures were lower than those of the chlorhexidine-free cultures, the total activity in the chlorhexidine-grown cultures was greater. PMID- 2318754 TI - Enhanced resistance to cefotaxime and imipenem associated with outer membrane protein alterations in Enterobacter aerogenes. AB - Mutants exhibiting enhanced resistance to cefotaxime and imipenem were selected by plating a strain of Enterobacter aerogenes, which already produced chromosomal beta-lactamase constitutively, on to varying concentrations of different beta lactam antibiotics. Frequencies of mutation varied from 10(-5) to 10(-8), depending upon the particular antibiotic and concentration used for selection. Only minor variations in beta-lactamase specific activities were observed and these could not be directly correlated with changes in resistance when compared with the original strain. In the majority of mutants, the selection of an enhanced level of resistance to cefotaxime was associated with a significant increase in resistance to imipenem, but no increase in resistance to the non-beta lactam antibiotics tested was observed. Examination of outer membrane protein profiles revealed a number of complex changes in the mutants when directly compared to the original strain. In one mutant imipenem/cefotaxime resistance was directly associated with almost total loss of a 42K protein which was non covalently associated with peptidoglycan and therefore possibly a porin protein. PMID- 2318755 TI - Plasma free and sulfoconjugated catecholamines during sustained exercise. AB - Previous research established a relationship between circulating sulfoconjugated norepinephrine (NE-SO4) and oxygen consumption at various exercise intensities. In this study, the stability of the NE-SO4 response was examined during sustained exercise at a constant relative intensity. Seven trained men bicycled at 78 +/- 3% of their maximal O2 consumption for 28 min and then rested on the ergometer for a comparable duration. After a 30-min rest, plasma samples were collected through an indwelling catheter at 7-min intervals during the exercise and recovery periods. Free NE and epinephrine increased sixfold during exercise. These changes were accompanied by increases in sulfoconjugated catecholamines, but only NE-SO4 achieved statistical significance (rest, 712 +/- 602; exercise, 1,329 +/- 1,163 pg/ml). This occurred at three collection periods (14, 21, and 28 min). Approximately 35, 52, and 95% of NE, epinephrine, and dopamine, respectively, existed as sulfoconjugated during exercise. Subject variation was present in the sulfoconjugated catecholamine response that could not be attributed to corresponding differences in circulating free catecholamine release. These findings implicate blood flow as a factor in the sulfoconjugation of NE, but not epinephrine or dopamine. PMID- 2318756 TI - Diameters, generations, and orders of branches in the bronchial tree. AB - Studies of bronchial tree data by West et al. (J. Appl. Physiol. 60: 1089-1097, 1986) have shown that plots of mean diameter against generation, using log-log scales, can be represented by a power function with harmonic modulations. Other studies have shown that the mean diameter of the airways is exponentially related to order of branching. This paper demonstrates that both observations are compatible with a fractal model of branching, and because airway branching is fractal, this may explain why both are also true of the bronchial tree. Furthermore, the exponential relationship of mean diameter with generation in the larger airways, demonstrated by Weibel, is shown to result from the exponential relation of diameter with order in the fractal model. PMID- 2318757 TI - Pulmonary vascular pressure-flow characteristics in canine pulmonary embolism. AB - We tested the hypothesis that, in canine embolic pulmonary hypertension, upstream transmission of increased left atrial pressure (LAP) is inversely related to the level of the pressure intercept (PI) obtained by extrapolation from the linear pulmonary vascular pressure-flow (P-Q) plot. P-Q coordinates were obtained by varying Q through systemic fistulas. Seven group 1 dogs were embolized with autologous blood clot to produce marked pulmonary hypertension and mean pulmonary arterial pressure (PAP), and PI increased from 15 to 41 mmHg (P less than 0.001) and from 8.8 to 31 mmHg (P less than 0.001), respectively. Before and after embolization we assessed effects of increased LAP, produced by inflation of a left atrial balloon, on PAP at constant Q. Embolization depressed the mean slope of this relationship from 0.78 to 0.16 (P less than 0.001). Subsequently, six group 2 dogs were embolized to produce moderate pulmonary hypertension with a mean PI of 22 mmHg. This value was significantly less than PI in group 1 (P less than 0.01). After embolization, the slope of the PAP-LAP relationship was greater in group 2 than group 1: 0.47 vs. 0.16 (P less than 0.01). We conclude that the upstream transmission of left atrial pressure is inversely related to PI and that marked embolic pulmonary hypertension produces an effective vascular waterfall. PMID- 2318758 TI - Contraction of smooth muscle of pig airway tissues from before birth to maturity. AB - Two heavy chains of smooth muscle myosin (MHC1 and MHC2) were identified in pig airways and parenchyma. The ratio of MHC1 to MHC2 was the same along the bronchial tree in animals of the same age, but it changed with age (mature, young, suckling, and fetus), ranging from 0.8 in the mature to 2.2 in the fetus. Stress developed in airway (trachea, bronchus, and bronchiole) and parenchymal preparations in response to carbachol and histamine (mN/mm2) was normalized for myosin content (N/mm2 myosin). Airways from sucklings always developed the greatest stress to carbachol and histamine with the rank order of maximum force (Emax) suckling greater than fetus greater than young greater than mature for carbachol in large airways. Airway ranking to histamine was similar except that Emax of fetal bronchus and bronchiole were least. In parenchymal strips, mature animals gave strong responses to carbachol and histamine compared with other age groups. Sensitivity to carbachol was increased in the suckling trachea; otherwise it did not vary with age. Chemically skinned tracheal fibers exhibited three- to fourfold greater sensitivity to Ca2+ in fetal and suckling airways compared with the older animals. It is concluded that maturation of smooth muscle occurs in the expression of myosin, in the Ca2(+)-force relationships of the contractile machinery, and in the pharmacological responsiveness of the intact smooth muscle, with the latter greatest at or soon after birth. PMID- 2318759 TI - Effect of superior vena caval hypertension on alloxan-induced lung injury in dogs. AB - To investigate how fast and to what extent superior vena caval hypertension (SVCH) increases lung water in acute increased-permeability state, we studied the time course of lung water accumulation for 3 h in anesthetized dogs under different treatments: 1) controls without intervention (5 dogs), 2) SVCH alone (5 dogs), 3) mild lung microvascular injury induced by low-dose alloxan (75 mg/kg) alone (5 dogs), and 4) SVCH coupled with low-dose alloxan (5 dogs). Neither low dose alloxan alone nor SVCH alone [superior vena caval pressure (Psvc) = 11.0 +/- 3.1 (SD) mmHg] increased lung water significantly. The SVCH coupled with low-dose alloxan (Psvc = 11.3 +/- 2.7 mmHg) doubled extravascular lung thermal volume measured by the thermal-dye dilution technique within 1 h (5.3 +/- 0.9 ml/kg at base line and 10.9 +/- 4.7 ml/kg at 1 h), then remained unchanged (12.5 +/- 5.7 ml/kg at 3 h). This increase in lung water was confirmed by gravimetric method (5.69 +/- 1.71 g/g blood-free dry wt). We conclude that SVCH is one of the factors that may promote lung water accumulation in increased-permeability state. PMID- 2318760 TI - Effect of lower rib cage expansion and diaphragm shortening on the zone of apposition. AB - The relationship among diaphragm length (LD), the width of the zone of apposition (WZapp), and transverse chest diameter (Drc) was developed from model equations and statistical analysis. We present a theoretical model of diaphragm motion that predicts that the decrease in WZapp during inspiration is the result not only of shortening of the diaphragm muscle but also of expansion of the lower rib cage. To test our model, static lengths of costal LD, WZapp, and Drc were measured in 15 normal volunteers using posteroanterior chest X-ray films taken at four or five lung volumes spanning the vital capacity. We found a strong correlation between WZapp and LD: WZapp = 0.95 LD - 15.2 (R2 = 0.81). Expressing WZapp as a combined function of LD and Drc significantly reduced the unexplained variance in WZapp: WZapp = 0.96 LD - 0.47 Drc - 2.18 (R2 = 0.95). The coefficients for LD and Drc derived statistically are close to those predicted from our theoretical model. Repeating the analysis with LD as the dependent variable, we obtained similar results: LD = 0.85 WZapp + 17.1 (R2 = 0.81) and LD = 0.98 WZapp + 0.46 Drc + 3.48 (R2 = 0.94). We conclude that shortening of WZapp is dependent on both diaphragm shortening and rib cage expansion and that roentgenographic measurements of Drc and WZapp can be used to predict diaphragm length and length change. PMID- 2318761 TI - Limb skeletal muscle adaptation in athletes after training at altitude. AB - Morphological and biochemical characteristics of biopsies obtained from gastrocnemius (GAS) and triceps brachii muscle (TRI), as well as maximal O2 uptake (VO2 max) and O2 deficit, were determined in 10 well-trained cross-country skiers before and after a 2-wk stay (2,100 m above sea level) and training (2,700 m above sea level) at altitude. On return to sea level, VO2 max was the same as the prealtitude value, whereas an increase in O2 deficit (29%) and in short-term running performance (17%) was observed (P less than 0.05). GAS showed maintained capillary supply but a 10% decrease in mitochondrial enzyme activities (P less than 0.05), whereas an increase in capillary supply (P less than 0.05) but unchanged mitochondrial enzyme activities were observed in TRI. Buffer capacity was increased by 6% in both GAS and TRI (P less than 0.05). A positive correlation was found between the relative increase in buffer capacity of GAS and short-term running time (P less than 0.05). Thus the present study indicates no effect of 2 wk of altitude training on VO2 max but provides evidence to suggest an improvement in short-term exercise performance, which may be the result of an increase in muscle buffer capacity. PMID- 2318762 TI - Spectral analysis of muscular sound during isometric contraction of biceps brachii. AB - The frequency content of muscular sound (MS), detected by placing a contact sensor transducer over the belly of the biceps brachii during 10 isometric contractions of 4 s each [10-100% of maximal voluntary contraction (MVC)] in seven sedentary men, was analyzed by the maximum entropy spectral estimation and the fast Fourier transform methods. With increasing %MVC, the power spectrum of the MS enlarges and tends to be multimodal beyond 30% MVC. Independent of the method, the mean frequency is approximately 11 Hz at the lower tasks, and then it increases up to 15 Hz at 80% MVC and to 22 Hz at 100% MVC. When the effort is increased the relative power in the 15- to 45-Hz bandwidth (range of firing rate of the motor units with fast-twitch fibers) from 20% reaches 55% of the power in the 6- to 45-Hz bandwidth (firing rate range of motor units with slow- and fast twitch fibers). Our results obtained by the two different modeling approaches confirm the reliability of the sound signal. Moreover, it appears that from the MS the motor unit activation pattern can be retrieved. PMID- 2318763 TI - Influence of the renin-angiotensin system on human forearm blood flow. AB - Although angiotensin II is a potent vasoconstrictor agent in all tissues, including the human forearm, equivocal effects on forearm blood flow (FBF) have been found after angiotensin blockade. In 13 healthy Na(+)-depleted subjects FBF was measured by the 133Xe washout technique; subcutaneous and muscle blood flows were determined separately. FBF was measured during supine rest, after the arm was lowered, and during lower body negative pressure (LBNP). The measurements were repeated during intra-arterial saralasin infusion in six subjects and after intravenous administration of enalapril in seven subjects. FBF decreased and forearm vascular resistance (FVR) increased during arm lowering and LBNP, as the result of local and central adrenergic reflexes, respectively. We observed similar FBF and FVR values after both saralasin and enalapril, except for a decrease in FVR at rest after enalapril. It is concluded that, in the human forearm, angiotensin II is not necessary for sympathetic vasoconstrictor reflexes but may, through a central effect, have some influence on arteriolar tone at rest. PMID- 2318764 TI - Running during recovery from hindlimb suspension induces transient muscle injury. AB - The objectives were to study morphological adaptations of soleus muscle to decreased loading induced by hindlimb suspension and the effect of run training during the subsequent recovery period. Adult female Wistar rats were kept for 28 days with hindlimbs suspended. For the next 28 days, rats were assigned to a cage sedentary or daily running group. Compared with control soleus muscles, 28 days of hindlimb suspension reduced the mass and fiber cross-sectional area to 58 and 53% of control values, respectively, and decreased type I fibers from 92 +/- 2 to 81 +/- 2%. During recovery, clusters of damaged fibers were observed in the soleus muscle, and this observation was more pronounced in trained animals. Type IIc fibers appeared transiently during recovery, and their presence was exacerbated with training, as IIc fibers increased to approximately 20% of the total by day 14 of recovery and were no longer evident at day 28. Although muscle wet mass does not differ as a result of mode of recovery at day 14, training transiently decreased the overall fiber area compared with sedentary recovery at this point. By day 28 of recovery the morphological characteristics of soleus muscle in the trained group did not differ from control muscle, whereas in the sedentary group muscle mass and overall fiber cross-sectional area were approximately 14% less than control values. PMID- 2318765 TI - Body composition and skin temperature variation. AB - Temperature variations near four common torso skin temperature sites were measured on 17 lightly clad subjects exposed to ambient temperatures of 28, 23, and 18 degrees C. Although variations in skin temperature exceeding 7 degrees C over a distance of 5 cm were observed on individuals, the mean magnitude of these variations was 2-3 degrees C under the coolest condition and less at the warmer temperatures. There was no correlation between the temperature variation and skinfold thickness at a site or with estimations of whole body fat content. These findings imply that errors in mean skin temperature measurement could arise from probe mislocation and/or subcutaneous fat distribution and that the problem becomes more acute with increasing cold stress. However, the magnitudes of these errors cannot be easily predicted from common anthropometric measurements. PMID- 2318766 TI - Inspiratory and expiratory muscle perfusion in maximally exercised ponies. AB - The present study was carried out on seven healthy ponies to examine the extent of blood flow in various inspiratory and expiratory muscles at rest and during maximal exertion as well as to determine the proportion of cardiac output needed to perfuse respiratory muscles during these conditions. Tissue blood flow was studied with 15 micron-diameter radionuclide-labeled microspheres injected into the left ventricle during steady conditions. The inspiratory and expiratory muscles comprised 2.41 and 3.05% of body weight, respectively, and received 6.17 and 3.75% of the cardiac output at rest. With maximal exercise, heart rate (from 55 +/- 3 to 218 +/- 4 beats/min), mean aortic pressure (from 125 +/- 5 to 170 +/- 6 mmHg), and cardiac output (from 96 +/- 11 to 730 +/- 78 ml.min-1.kg-1) increased markedly. During exercise blood flow increased significantly in all respiratory muscles (P less than 0.0001) as vascular resistance decreased precipitously. Marked heterogeneity of perfusion existed among various inspiratory as well as expiratory muscles during exercise. Among the inspiratory muscles, the highest perfusion occurred in the diaphragm followed by serratus ventralis, and among the expiratory muscles, the highest perfusion occurred in the internal oblique abdominis and the transverse thoracis (triangularis sterni). Collectively, the inspiratory (8.44%) and expiratory (6.35%) muscle blood flow comprised 14.8 +/- 1.2% of the cardiac output during maximal exercise, a significant increase above resting value, whereas renal fraction of cardiac output decreased from 21% (at rest) to 0.72%. PMID- 2318767 TI - Endotoxin protection of rats from pulmonary oxygen toxicity: possible cytokine involvement. AB - Treatment with endotoxin protects rats against lung injury during hyperoxia (greater than 98% oxygen at 1 atmosphere absolute for 60 h). This study demonstrates that serum from endotoxin-treated donor rats also protects recipients from oxygen toxicity. Rats treated with serum from saline-treated donors were not protected, and protection was not explained by residual endotoxin in protective sera. Unlike endotoxin-protected rats (where lung antioxidant enzyme activity is elevated after hyperoxia), postexposure superoxide dismutase (SOD) and catalase (CAT) activities in the lungs of serum-protected rats were not affected. Levels of tumor necrosis factor (TNF) and interleukin 1 (IL-1) in protective sera were increased. This study demonstrates that increases in lung SOD and CAT activity are not required for endotoxin protection from hyperoxia and suggests that TNF and IL-1 may participate in the mechanism of endotoxin protection. PMID- 2318768 TI - Age-related effects of compression rate and duration in cardiopulmonary resuscitation. AB - The effects of various compression rate and duration combinations on chest geometry and cerebral perfusion pressure during cardiopulmonary resuscitation (CPR) were studied in immature swine. Pentobarbital-anesthetized 2- and 8-wk-old piglets received CPR after ventricular fibrillation. At compression rates of 40, 60, 80, 100, 120, and 150/min, duty cycle (compression duration/total cycle time) was increased from 10 to 80% by 10% increments. Mean aortic and sagittal sinus pressures, pulsatile displacement, and deformity of the anterior chest wall were measured. Increasing duty cycle increased cerebral perfusion pressure until chest relaxation time was compromised. Inadequate chest recoil, development of static chest deformation, and limitation of pulsatile chest wall movement occurred in both age groups when relaxation time was very short (150-200 ms in 2-wk-old piglets, 250-300 ms in 8-wk-old piglets). These changes in chest geometry correlated with deterioration of cerebral perfusion pressure only in 8-wk-old piglets. In the younger group, perfusion pressures plateaued but did not deteriorate. These data emphasize the importance of duty cycle in generating cerebral perfusion pressure and indicate that younger animals can tolerate high compression rates except at extremely long duty cycles. PMID- 2318769 TI - Cardiovascular responses to exercise in the rat: role of corticotropin-releasing factor. AB - The effects of intracerebroventricular (icv) administration of a corticotropin releasing factor (CRF) receptor antagonist, alpha-helical CRF, on systemic and regional hemodynamic adjustments to exercise were studied in conscious rats. On consecutive days, rats received saline icv, alpha-helical CRF icv, and no treatment 30 min before treadmill exercise (TMX). Increases in heart rate (HR) and mean arterial pressure (MAP) in response to TMX (16.1-28.6 m/min) were similar after icv administration of saline or no treatment. In rats receiving saline icv or no treatment, estimated vascular resistance increased in the mesenteric and renal regions and declined in the iliac (hindlimb) region. After icv administration of alpha-helical CRF9-41, HR and MAP responses during TMX were significantly attenuated. In addition, TMX-induced elevations of estimated mesenteric vascular resistance and iliac blood flow velocity were blunted after CRF receptor blockade. These altered cardiovascular and hemodynamic responses were ultimately reflected in the animals' compromised ability to run. The results suggest that the central nervous system actions of endogenous CRF are necessary for the full expression of the cardiovascular adjustments to TMX in the conscious rat. PMID- 2318770 TI - Enhancement of maximal thermogenesis by reducing endogenous adenosine activity in the rat. AB - Adenosine has been shown in vitro to be a potent antilipolytic agent and an inhibitor of insulin-stimulated glucose utilization in skeletal muscle. To test whether endogenously produced adenosine (e.g., from ATP hydrolysis) shares these deleterious effects on substrate mobilization and utilization and thus limits maximum thermogenesis in vivo, adenosine deaminase (converts adenosine to inosine) was given to rats 15 min before cold exposure. Significant (P less than 0.05) increases in thermogenesis were observed under both well-fed (100 units/kg ip) and food-rationed (200 units/kg ip) states. Significant (P less than 0.05) increases in thermogenesis and cold resistance were also observed after pretreatment with selective adenosine receptor antagonists [8 cyclopentyltheophylline (1 microgram/kg ip) greater than 1,3-dipropyl-8-p sulfophenylxanthine (1.25 mg/kg ip) greater than aminophylline (18.7 mg/kg ip)], indicating an A1-receptor-mediated effect. These results indicate that endogenously released adenosine can indeed attenuate the thermogenic capacity in severe cold and that adenosine antagonists, especially those selective for A1 receptor, are useful in improving cold resistance under varying nutritional states. PMID- 2318771 TI - Reactive uptake governs the pulmonary air space removal of inhaled nitrogen dioxide. AB - With the use of an isolated rat lung model, we investigated pulmonary air space absorption kinetics of the reactive gas NO2 in an effort to determine the contributory role of chemical reaction(s) vs. physical solubility. Unperfused lungs were employed, because vascular perfusion had no effect on acute (0- to 60 min) NO2 absorption rates. We additionally found the following: 1) Uptake was proportional to exposure rates (2-14 micrograms NO2/min; 10-63 ppm; 37 degrees C) but saturated with exposures greater than or equal to 14 micrograms NO2/min. 2) Uptake was temperature (22-48 degrees C) dependent but, regardless of temperature, attained apparent saturation at 10.6 micrograms NO2/min. 3) Lung surface area (SA) was altered by increasing functional residual capacity (FRC). Expanded SA (8 ml FRC) and temperature (48 degrees C) both raised fractional uptakes (greater than or equal to 0.81) relative to 4 ml FRC, 37 degrees C (0.67). Uptake rates normalized per unit estimated SA revealed no independent effect of FRC on fractional uptake. However, temperature produced a profound effect (48 degrees C = 0.93; 4 and 8 ml FRC = 0.54). 4) Arrhenius plots (ln k' vs. 1/T), which utilized derived reactive uptake coefficients (k'), showed linearity (r2 = 0.94) and yielded an activation energy of 7,536 kcal.g-1.mol-1 and Q10 of 1.43, all consistent with a reaction-mediated process. These findings, particularly the effects of temperature, suggest that acute NO2 uptake in pulmonary air spaces is, in part, rate limited by chemical reaction of NO2 with epithelial surface constituents rather than by direct physical solubility. PMID- 2318772 TI - Effects of acetazolamide on metabolic and respiratory responses to exercise at maximal O2 uptake. AB - Changes in blood gases, ions, lactate, pH, hemoglobin, blood temperature, total body metabolism, and muscle metabolites were measured before and during exercise (except muscle), at fatigue, and during recovery in normal and acetazolamide treated horses to test the hypothesis that an acetazolamide-induced acidosis would compromise the metabolism of the horse exercising at maximal O2 uptake. Acetazolamide-treated horses had a 13-mmol/l base deficit at rest, higher arterial Po2 at rest and during exercise, higher arterial and mixed venous Pco2 during exercise, and a 48-s reduction in run time. Arterial pH was lower during exercise but not in recovery after acetazolamide. Blood temperature responses were unaffected by acetazolamide administration. O2 uptake was similar during exercise and recovery after acetazolamide treatment, whereas CO2 production was lower during exercise. Muscle [glycogen] and pH were lower at rest, whereas heart rate, muscle pH and [lactate], and plasma [lactate] and [K+] were lower and plasma [Cl-] higher following exercise after acetazolamide treatment. These data demonstrate that acetazolamide treatment aggravates the CO2 retention and acidosis occurring in the horse during heavy exercise. This could negatively affect muscle metabolism and exercise capacity. PMID- 2318773 TI - Influence of single hindlimb support during simulated weightlessness in the rat. AB - Mature male rats (n = 16) were assigned to either 14 days of head-down suspension with one hindlimb supported (HDS) or to control cages (C) of similar dimensions. Hindlimb support during HDS preserved the muscle mass-to-body mass ratio (mg/100g) compared with C conditions for the soleus (48.3 +/- 1.0 to 41.7 +/- 1.0), plantaris (98.4 +/- 3.4 to 103.3 +/- 4.1), and gastrocnemius (484.7 +/- 18.5 to 507.2 +/- 13.9). However, the muscle mass-to-body mass ratio was significantly lower for the soleus (28.9 +/- 1.5), plantaris (83.9 +/- 3.6), and gastrocnemius (411.9 +/- 24.2) muscles from the freely hanging hindlimbs compared with the contralateral muscles from the supported hindlimbs or muscles from C animals. Citrate synthase activity (mumol.g-1.min-1) was significantly lower in soleus muscles from HDS rats in both the supported (19.4 +/- 2.3) and freely hanging (20.0 +/- 1.6) hindlimbs compared with C (28.5 +/- 3.1), whereas soleus muscle glycogen concentration (mg/g) was significantly higher in the freely hanging limbs from HDS rats (5.90 +/- 0.31) but not in the supported limbs (3.80 +/- 0.61) compared with C (4.34 +/- 0.50). Doppler flow probes were used to determine that iliac blood flow to freely hanging hindlimbs was significantly decreased after 48 (-19 +/- 5%) and 72 (-20 +/- 6%)h of HDS compared with presuspension values. In addition, iliac vascular resistance was significantly elevated at most time points during the 72 h of HDS in the freely hanging limbs but not the supported hindlimbs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318774 TI - Effect of age on changes in flow rates and airway conductance after a deep breath. AB - The effects of aging on changes in maximal expiratory flow rates and specific airway conductance after a deep breath were evaluated in 64 normal subjects. Flow rates (Vp) on partial expiratory flow-volume curves (PEFV), initiated from 60-70% of the vital capacity (VC), were compared with those (Vc) on maximal flow-volume curves (MEFV), initiated from total lung capacity (TLC), at a lung volume corresponding to 25% of VC on the MEFV curves. Specific airway conductance was measured before (sGaw) and after a deep inspiration (sGawDI). Bronchodilation after inspiration to TLC was inferred by Vp/Vc less than 1 and sGaw/sGawDI less than 1. The mean Vp was less than Vc. However, the ratio Vp/Vc increased significantly with age (r = 0.75, P less than 0.001). Specific conductance also increased after a deep inspiration (sGaw less than sGawDI). The ratio sGaw/sGawDIj increased slightly but significantly with age (r = 0.28, P less than 0.02). Measurement of lung elastic recoil pressures before and after a deep breath in a subgroup of patients (n = 14) suggested that the age-related increase in Vp/Vc was secondary to a decrement in the ability of a deep breath to decrease the upstream airway resistance. These findings suggest that even though changes in airway size after a deep breath as measured by sGaw/sGawDI have minimal age dependence, aging diminishes expiratory flow rates of MEFV curves relative to PEFV curves because of a decrease in the ability of a deep breath to increase the size of the peripheral airways. PMID- 2318775 TI - 31P-NMR spectroscopy and the metabolic properties of different muscle fibers. AB - To study the in vivo recruitment of different fiber types and their metabolic properties, 31P-nuclear magnetic resonance spectroscopy (31P-NMRS) of the human calf muscle was performed in seven normal sedentary subjects. In the exhaustive exercise protocol used, the work load was increased every minute during 5 min. This resulted in a prominent split of the Pi resonance in all subjects, indicating pH compartmentation in the muscles studied. From the chemical shift of the Pi peaks relative to phosphocreatine (PCr) at the end of the exercise, intracellular pH (pHi) averaged 6.92 +/- 0.05 (SD) in compartment 1 and 6.23 +/- 0.15 in compartment 2. The recovery of both Pi resonances after exercise could be followed easily in five of these subjects. The recovery rate of the Pi peak is a good estimate of the oxidative metabolism at the end of the exercise. A monoexponential regression analysis showed that the mean initial recovery rate S0 was 2.49 +/- 0.17%/s in compartment 1 and only 0.87 +/- 0.12%/s in compartment 2, indicating aerobic function three times higher in compartment 1 at the end of exercise. The mean relative ATP fraction dropped significantly (P less than 0.001), from 20.0 +/- 1.0% of the total 31P signal integral before exercise to 14.0 +/- 1.6% at the end of exercise. The simultaneous visualization of two compartments, in good order, one with high pHi and fast recovery and another with low pHi and slow recovery, is rationalized by the different metabolic behavior of type I and II fibers in human calf muscle in response to exhaustive exercise. This study demonstrates that 31P-NMRS is an excellent noninvasive procedure to quantify aerobic metabolism in both fiber types simultaneously. PMID- 2318776 TI - Role of concentric force in limiting improvement in muscular strength. AB - We hypothesized that resistance training with combined eccentric and concentric actions, and concentric action only, should yield similar changes in muscular strength. Subjects in a free weight group trained three times a week for 12 wk with eccentric and concentric actions (FW, n = 16), a second group trained with concentric-only contractions using hydraulic resistance (HY; n = 12), and a control group did not train (n = 11). Training for FW and HY included five sets of supine bench press and upright squat at an intensity of 1-6 repetition maximum (RM) plus five supplementary exercises at 5-10 RM for a total of 20 sets per session for approximately 50 min. Testing at pre-, mid-, and posttraining included 1) 1 RM bench press and squat with and 2) without prestretch using free weights; 3)isokinetic peak force and power for bench press and squat at 5 degrees/s, and isotonic peak velocity and power for bench press with 20-kg load and squat with 70-kg load; 4) hydraulic peak bench press force and power, and peak knee extension torque and power at fast and slow speeds; and 5) surface anthropometry (fatfolds and girths to estimate upper arm and thigh volume and muscle area). Changes in overall fatness, muscularity, and muscle + bone cross sectional area of the limbs did not differ between groups (P greater than 0.05). Improvements in free weight bench press and squat were similar (P greater than 0.05) in FW (approximately 24%) and HY (approximately 22%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318777 TI - Changes in insulation of body tissue and wet suits during underwater exercise at various atmospheric pressures. AB - To clarify the independent changes of insulations of body tissues (Itissue) and wet suit (Isuit) in the wet-suited subject during underwater exercise, overall heat flow from the skin (Htissue) and wet suit (Hsuit) and esophageal (Tes), skin (Tsk), and wet suit temperatures were measured at 1, 2, and 2.5 atmospheres absolute (ATA) at critical water temperature (Tcw). The average Tcw in nine wet suited men (23-38 yr) was 22.3 +/- 0.2, 26.3 +/- 0.2, and 28.0 +/- 0.4 degrees C (SE) at 1, 2, and 2.5 ATA, respectively. At Tcw of each pressure male volunteers wearing 5-mm neoprene wet suits completed three 2-h experiments while immersed up to the neck. During one experiment the subjects remained at rest, and in the other two they exercised on an underwater ergometer at two different intensities (2 and 3 met). Tes significantly declined (P less than 0.05) over 2 h from 37.1 to 36.5 degrees C during rest in each pressure. The 2-met exercise prevented Tes from falling in all pressures, and the 3-met exercise elevated Tes by 0.2-0.3 degrees C. There was no exercise-dependent difference in Isuit, but a pressure dependent difference was remarkable. The Itissue at rest was identical for all pressures; however, it progressively decreased as a function of exercise intensity. It is concluded that overall Itissue is entirely determined by work intensity at Tcw, but not by atmospheric pressure. On the contrary, Isuit at Tcw is solely dependent on the pressure, but not on the work intensity. PMID- 2318778 TI - Respiratory impedance to ambient pressure changes at low frequencies. AB - Respiratory impedance may be studied by measuring airway flow (Vaw) when pressure is varied at the mouth (input impedance) or around the chest (transfer impedance). A third possibility, which had not been investigated so far, is to apply pressure variations simultaneously at the two places, that is to vary ambient pressure (Pam). This provides respiratory impedance to ambient pressure changes (Zapc = Vaw/Pam). In that situation airway impedance (Zaw) and tissue impedance (Zt) are mechanically in parallel, and both are in series with alveolar gas impedance (Zg): Zapc = Zaw + Zg + Zaw.Zg/Zt. We assessed the frequency dependence of Zapc from 0.05 to 2 Hz in nine normal subjects submitted to sinusoidal Pam changes of 2-4 kPa peak to peak. The real part of Zapc (Rapc) was of 6.2 kPa.1(-1).s at 0.05 Hz and decreased to 1.9 kPa.1(-1).s at 2 Hz. Similarly the effective compliance (Capc), computed from the imaginary part of Zapc, decreased from 0.045 1.kPa-1 at 0.05 Hz to 0.027 1.kPa-1 at 2 Hz. Breathing against an added resistance of 0.46 kPa.1(-1).s exaggerated the negative frequency dependence of both Rapc and Capc. When values of airway resistance and inertance derived from transfer impedance data were introduced, Zapc was used to compute effective tissue resistance (Rt) and compliance (Ct). Rt was found to decrease from 0.32 to 0.15 kPa.1(-1).s and Ct from 1.11 to 0.64 1.kPa-1 between 0.25 and 2 Hz. Ct was slightly lower with the added resistance. These results are in good agreement with the data obtained by other approaches. PMID- 2318779 TI - Upper airway muscle and diaphragm responses to hypoxia in the piglet. AB - The neonatal ventilatory response to hypoxia is characterized by initial transient stimulation and subsequent respiratory depression. It is unknown, however, whether this response is also exhibited by the upper airway muscles that regulate nasal, laryngeal, and pharyngeal patency. We therefore compared electromyogram (EMG) amplitudes and minute EMGs for the diaphragm (DIA), alae nasi (AN), posterior cricoarytenoid (PCA), and genioglossus (GG) muscles in 12 anesthetized spontaneously breathing piglets during inhalation of 12% O2 over 10 min. Minute EMG for the DIA responded to hypoxia with an initial transient increase and subsequent return to prehypoxia levels by 10 min. Hypoxia also stimulated all three upper airway muscles. In contrast to the DIA EMG, however, AN, PCA, and GG EMGs all remained significantly above prehypoxia levels after 10 min of hypoxia. We have thus demonstrated that the initial stimulation and subsequent depression of the DIA EMG after 12% O2 inhalation contrast with the sustained increase in AN, PCA, and GG EMGs during hypoxia. We speculate that 1) central inhibition during neonatal hypoxia is primarily distributed to the motoneuron pools regulating DIA activation and 2) peripheral chemoreceptor stimulation and/or central disinhibition induced by hypoxia preferentially influence those motoneuron pools that regulate upper airway muscle activation, causing the different hypoxic responses of these muscle groups in the young piglet. PMID- 2318780 TI - Cardiovascular responses to hypoxia and hypercapnia in barodenervated rats. AB - Experiments were performed to examine the role of the arterial baroreceptors in the cardiovascular responses to acute hypoxia and hypercapnia in conscious rats chronically instrumented to monitor systemic hemodynamics. One group of rats remained intact, whereas a second group was barodenervated. Both groups of rats retained arterial chemoreceptive function as demonstrated by augmented ventilation in response to hypoxia. The cardiovascular effects to varying inspired levels of O2 and CO2 were examined and compared between intact and barodenervated rats. No differences between groups were noted in response to mild hypercapnia (5% CO2); however, the bradycardia and reduction in cardiac output observed in intact rats breathing 10% CO2 were eliminated by barodenervation. In addition, hypocapnic hypoxia caused a marked fall in blood pressure and total peripheral resistance (TPR) in barodenervated rats compared with controls. Similar differences in TPR were observed between the groups in response to isocapnic and hypercapnic hypoxia as well. It is concluded that the arterial baroreflex is an important component of the overall cardiovascular responses to both hypercapnic and hypoxic stimuli in the conscious rat. PMID- 2318781 TI - Mechanism of ethanol-induced vasodilation. AB - The mechanism by which ethanol ingestion causes dermal vasodilation is unclear, but it may result from a direct action on central vascular control mechanisms. Forearm blood flow and peripheral skin temperatures were examined in five quadriplegics (lesions above T7) and five control subjects, before and after the ingestion of ethanol (0.75 ml/kg body wt). The lack of vasomotor efferent function was confirmed in the quadriplegics by the absence of vasodilation in response to radiant heating of the torso. There were no significant changes in peripheral temperatures or forearm blood flow after ethanol in the quadriplegics. The control subjects had a significant increase in forearm blood flow (1.12 +/- 0.2 ml.min-1.100 ml-1) and skin temperature (finger 2.4 +/- 0.4 degrees C, toe 3.4 +/- 0.3 degrees C) after ethanol. These data suggest that ethanol may induce peripheral vasodilation by modulation of central vasomotor control mechanisms. PMID- 2318782 TI - Energy expenditure during bicycling. AB - This study was designed to measure the O2 uptake (VO2) of cyclists while they rode outdoors at speeds from 32 to 40 km/h. Regression analyses of data from 92 trials using the same wheels, tires, and tire pressure with the cyclists riding in their preferred gear and in an aerodynamic position indicated the best equation (r = 0.84) to estimate VO2 in liters per minute VO2 = -4.50 + 0.17 rider speed + 0.052 wind speed + 0.022 rider weight where rider and wind speed are expressed in kilometers per hour and rider weight in kilograms. Following another rider closely, i.e., drafting, at 32 km/h reduced VO2 by 18 +/- 11%; the benefit of drafting a single rider at 37 and 40 km/h was greater (27 +/- 8%) than that at 32 km/h. Drafting one, two, or four riders in a line at 40 km/h resulted in the same reduction in VO2 (27 +/- 7%). Riding at 40 km/h at the back of a group of eight riders reduced VO2 by significantly more (39 +/- 6%) than drafting one, two, or four riders in a line; drafting a vehicle at 40 km/h resulted in the greatest decrease in VO2 (62 +/- 6%). VO2 was also 7 +/- 4% lower when the cyclists were riding an aerodynamic bicycle. An aerodynamic set of wheels with a reduced number of spokes and one set of disk wheels were the only wheels to reduce VO2 significantly while the cyclists were riding a conventional racing bicycle at 40 km/h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318783 TI - Analysis of pulmonary arterial pressure profile after occlusion of pulsatile blood flow. AB - In isolated canine lung lobes perfused with a pulsatile pump, arterial occlusions were performed and the postocclusion arterial pressure profiles were analyzed to estimate the pulmonary capillary pressure. A solenoid valve interposed between the pump and the lobar artery was used to perform arterial occlusions at several instants equally distributed within a pressure cycle. Double occlusions were also accomplished by simultaneously activating the solenoid valve and clamping the venous outflow of the lung lobe. To analyze an arterial occlusion pressure profile, we computed the best monoexponential fit of the pressure decay over a short period of time after the occlusion maneuvers. Two estimates of the capillary pressure were derived from this analysis: 1) the extrapolation of the exponential fit to the instant of occlusion, and 2) the point at which the recorded pressure decay curve merges with the exponential fit. The pressures thus determined were compared with the double occlusion pressure that provided an independent estimate of the pulmonary capillary pressure. Our results show that, under a wide range of conditions, the estimates of the capillary pressure obtained from the arterial occlusion data are nearly equal to the double occlusion pressures. Additionally, we estimated the capillary pressure variations within a pressure cycle by examining the occlusion pressures sampled at different instants of the cycle. The pulsatility of the pulmonary microvascular pressure varied with the pump frequency as well as the state of arterial and venous vasoaction. These variations are consistent with the representation of the lung vasculature as a low-pass filter. PMID- 2318784 TI - Alveolar dead space does not affect indirect Fick cardiac output determinations. AB - We examined the influence of three variables (different breathing circuits, breath selected for analysis, and alveolar dead space ventilation) on the accuracy of noninvasive cardiac output determinations with the Fick CO2 (indirect) equation. We compared noninvasive determinations with invasive thermodilution measurements over a wide range of cardiac outputs in 17 2-mo-old pigs anesthetized with halothane and nitrous oxide and paralyzed with either pancuronium or d-tubocurare. We found that rebreathing and nonrebreathing circuits provide accurate cardiac output determinations and that the optimal breath for analysis with either the rebreathing or nonrebreathing technique appears to depend on the cardiac output. When alveolar dead space was increased by using positional changes and the intracardiac administration of glass beads, there was still a good correlation between noninvasive and invasive cardiac output determinations. We conclude that both rebreathing and nonrebreathing techniques of indirect Fick cardiac output determinations correlate well with thermodilution measures over a wide range of cardiac outputs and alveolar dead space/tidal volume fractions. PMID- 2318785 TI - Tracheal dead space influences regional ventilation measurement in dogs. AB - The lung volume at which airway closure begins during expiration (closing volume, CV) can be measured 1) with a radioactive bolus inspired at residual volume (RV) and 2) with the single-breath N2 elimination test. In previous studies in dogs, we observed that N2 CV was systematically larger than 133Xe bolus CV (Xe CV) [N2 CV %vital capacity (VC) = 35 +/- 2.3 (SE) vs. Xe CV %VC = 24 +/- 2.2, P less than 0.01]. Because the regional RV in the dog is evenly distributed throughout the lung and all airways closed at RV, N2 CV is related to the regional distribution of the tracheal N2; differences between N2 and Xe CV could then be related to the size of the inhaled dead space. Simultaneous measurements of Xe and N2 CV were performed at various sites of Xe bolus injection while the regional distribution of the bolus was measured. Injections at the level of the carina increased Xe CV to a value (30 +/- 1.4%VC) near simultaneous N2 CV (32 +/- 1.5%VC) and increased the unevenness of regional distribution of the Xe bolus. The difference between N2 and Xe CV is then the result of the size of the inspired tracheal dead space. Moreover, comparisons between different values of Xe CV require injections of the boluses at the same distance from the carina. PMID- 2318786 TI - Investigation of VO2 kinetics in humans with pseudorandom binary sequence work rate change. AB - The dynamic response of oxygen uptake (VO2) was investigated with two different cycle ergometer tests in which the work rate changed as a pseudorandom binary sequence (PRBS). One sequence had 15 units, each of 30-s duration for a total of 450 s (PRBS1). The second had 63 units, each of 5-s duration for a total of 315 s (PRBS2). The useful range of frequencies available for investigation of the dynamic characteristics of the VO2 response as described by their bandwidth were 0.002-0.013 Hz for PRBS1 and 0.003-0.089 Hz for PRBS2. Eight subjects each completed both PRBS tests. Data from four or five consecutive sequences were ensemble averaged to reduce the biological noise. A Fourier analysis was then conducted, with the range of frequencies investigated spanning those of the bandwidth for PRBS2. This was up to the 28th harmonic. For PRBS1, the VO2 response could be adequately reconstructed by including Fourier coefficients only up to the 5th harmonic. In contrast, for PRBS2, there was still a clear pattern in the residuals at the 5th harmonic. The data were not adequately reconstructed until higher-frequency components up to the 28th harmonic were included. Evidence for this came from analysis of the mean square error. The mean square error at the 28th harmonic was reduced to 83 +/- 8% of the mean square error at the 5th harmonic for PRBS1 and to 31 +/- 3% for PRBS2 (P less than 0.0001). These data obtained by Fourier analysis and reconstructed for comparison with the original VO2 response indicate the presence of a high-frequency component that was not apparent when a test with a smaller bandwidth was used as the work rate forcing. PMID- 2318787 TI - Adaptation of the inert gas FRC technique for use in heavy exercise. AB - We automated the inert gas rebreathe technique for measurement of end-expiratory lung volume (EELV) during heavy exercise. We also assessed the use of two gas tracers (He and N2) vs. a single gas tracer (He) for measurement of this lung volume and compared the two-tracer EELV to changes in the inspiratory capacity (defined with transpulmonary pressure) and shifts in the end-expiratory pressure from rest through heavy exercise. A computer program switched a pneumatic valve when flow crossed zero at end expiration and defined points in the He and N2 traces for calculation of EELV. An inherent delay of the rebreathing valve (50 ms) caused virtually no error at rest and during light exercise and an error of 74 +/- 9 ml in the EELV at peak inspiratory flow rates of 4 l/s. The measurement of EELV by the two gas tracers was closely correlated to the single-gas tracer measurement (r = 0.97) but was consistently higher (120 +/- 10 ml) than when He was used alone. This difference was accentuated with increased work rates (2-5% error in the EELV, rest to heavy exercise) and as rebreathe time increased (2-7% error in the EELV with rebreathe times of 5-20 s for all work loads combined). The double-gas tracer measurement of EELV agreed quite well with the thoracic gas volume at rest (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2318788 TI - Biological heterogeneity and radiation sensitivity of in vitro propagated lung metastatic lines originated from a transplantable squamous cell carcinoma of BALB/c mouse. AB - Seven cell lines established from a diethylnitrosamine (DEN)-induced forestomach carcinoma (DEN3) of a BALB/c mouse and its six pulmonary metastatic foci were used to study the biological and functional diversity of tumor cells. DEN3 is a highly tumorigenic line capable of forming lung metastases readily. Six metastatic nodules were isolated from the lungs of syngeneic mice and six cell lines were established. The cell lines differed in characteristics such as tumorigenicity, metastatic capability, and in vivo and in vitro growth properties. Radiation sensitivity of these cell lines was examined by exposure, at near confluency stage of in vitro growth, to doses of 2.5 to 50 Gray (Gy) X rays (1 Gy = 100 rads). Shortly after exposure (approximately 5 min), the cells were harvested and 10(5) cells were cultured or inoculated into syngeneic mice, or both. Growth of three of the six cell lines tested was prohibited by 5 Gy. However, some populations from the other cell lines were able to survive 5 or 10 Gy. Progenies of the cells that survived primary radiation exposure after several in vitro passages were able to withstand another exposure of the same magnitude but not a higher dose. The X-rayed survivor cells also maintained their tumorigenic potential. PMID- 2318789 TI - Isolated trout liver cells: establishing short-term primary cultures exhibiting cell-to-cell interactions. AB - Composition and interactions of cell types in rainbow trout (Oncorhynchus mykiss) liver digested with collagenase and cultured in serum-free media were investigated. Suspensions obtained after digesting trout liver with collagenase contained all the cell types present in the liver, including liver parenchymal cells (hepatocytes), biliary epithelial cells, sinusoidal endothelium, fat storing cells of Ito, and macrophages. A major cell pellet, mainly hepatocytes but containing significant numbers of biliary epithelial cells, was obtained by centrifuging the cell suspension at 120 X g for 1 min. Cells present in this pellet quantitatively attached to culture plates coated with a trout skin extract and remain attached for 4 to 6 d with good retention of intracellular enzymes and DNA. When in culture, significant changes in and among the cells were observed. Initial preparations were rounded, single cells. Within several hours, however, cellular interactions leading to aggregation became evident and aggregates increased in size for 2 to 3 d. Scanning electron microscopy (EM) showed frequent shaftlike projections from margins of the aggregates. Transmission EM indicated that these projections represent biliary ductules forming in vitro. Adjacent hepatocytes also showed plasma membrane specializations forming junctional complexes and canaliculi characteristics of normal trout liver. After 5 to 6 d in culture, significant numbers of the cell aggregates dislodged from the plate. Analysis showed the dislodged cells were viable but vacuolated. The reestablishment in vitro of morphologic relationships resembling in situ tissue components suggest these culture preparations may have significant utility in cooperative metabolic studies of cell interactions in trout liver. PMID- 2318790 TI - Induction of distinct phenotypes in clonal and variant GH4 pituitary cells. AB - GH cells are a widely used cell strain for the investigation of mechanisms regulating hormone release and synthesis. This report identifies two inducible phenotypes of the GH4 clone (epithelioid and motile) which may extend studies of this well-characterized cell line to different stages of pituitary cell development. GH4C1 cells treated in suspension with epidermal growth factor plus tetradecanoylphorbol acetate aggregate to form large epithelioid colonies with extensive cell-to-cell and cell-to-substratum adhesion. These cells cease replicating within 48 h, increase 50% in cell volume, and synthesize 40-fold more prolactin. A GH4C1 variant with enhanced substratum adhesion and little or no cell-to-cell adhesion (GH4S1), responds differently to this treatment. These cells cease replicating immediately, show increased cell separation, develop leading lamellae, and display locomotory activity. Each phenotype coexists in mixed cultures of GH4C1 and GH4S1 cells. This indicates that the different inducible response of the variant does not result from autocrine secretion. A molecular basis for cell-to-cell adhesion in GH4 cells was investigated. GH4C1, but not the variant cells, express a 180 kDa immunoreactive protein indistinguishable from an isoform of the neural cell adhesion molecule. Therefore the absence of cell-to-cell adhesion and inability to develop extensive cell-to cell adhesion characteristic of the epithelioid phenotype may result from altered expression of the neural cell adhesion molecule. These findings are important because they have defined an in vitro approach to investigate genetic and cellular changes associated with the development and progression of pituitary cell phenotype. PMID- 2318791 TI - Effects of ascorbate on myogenesis in micromass culture. AB - Micromass cultures from stage 23 and 24 chick wing mesenchyme were grown in serum containing medium with or without additional ascorbic acid. It was found that ascorbic acid administered as a single pulse or present continuously throughout culture, in concentrations as low as 25 micrograms/ml, was sufficient to abolish 80% of myogenesis as assessed by immunolocalization using muscle-specific antibodies. This effect was not significantly altered when cultures were maintained in a serum-free medium that promotes myogenesis. In contrast to the above findings, spectrophotometric analysis of accumulated sulphated glycosaminoglycans, an indicator of chondrogenesis, was elevated by ascorbate treatment. Furthermore, a similar level of glycosaminoglycan stimulation was found in ascorbate treated stage 23 distal-tip limb cultures that were essentially free of myogenic cells. We conclude, therefore, that the presence of myoblasts in whole-limb cultures has no appreciable inhibitory effects on chondrogenesis. PMID- 2318792 TI - Riboflavin deficiency in cultured rat hepatoma cells: a model for studying the hepatic effects of riboflavin deficiency. AB - The acyl-CoA dehydrogenases are a family of mitochondrial flavoenzymes required for fatty acid beta-oxidation and branched-chain amino acid degradation. The hepatic activity of these enzymes, particularly the short-chain acyl-coenzyme A (CoA) dehydrogenase, is markedly decreased in riboflavin deficient rats. We now report that the in vivo effects of riboflavin deficiency on the beta-oxidation enzymes of this group are reproduced in FAO rat hepatoma cells cultured in riboflavin-deficient medium. Although it has been long known that hepatic short chain acyl-CoA dehydrogenase activity is the most severely affected of the straight-chain specific enzymes in riboflavin deficiency, the mechanism by which its activity is decreased has not been reported. We have used this new cell culture system to characterize further this mechanism. Whole cell extracts from riboflavin-deficient and control cells were subjected to analysis by denaturing polyacrylamide gel electrophoresis. The contents of the gels were then electroblotted onto nitrocellulose filters and probed with short-chain acyl-CoA dehydrogenase-specific antiserum. The relative abundance of enzyme antigen was estimated autoradiographically. Our findings indicate that short-chain acyl-CoA dehydrogenase activity changes in parallel with its antigen, suggesting that riboflavin deprivation does not affect the activity of individual enzyme molecules. Further, no evidence of extramitochondrial enzyme precursor was found on the blots, making unlikely a significant block in the mitochondrial uptake process. These findings suggest that changes in short-chain acyl-CoA dehydrogenase activity in riboflavin deficiency result from either increased synthesis or decreased degradation of the enzyme. PMID- 2318794 TI - [Proton spin tomography in the evaluation of lung tumor invasiveness into the mediastinum]. AB - The study of tumor extension and the diagnosis of invasion of the mediastinum are important features in the pre-operative staging of a lung tumor. MRI appears to be helpful. This paper gives a brief summary of the potentials and pitfalls of this technique. PMID- 2318793 TI - Isolation and characterization of endothelial cells from bovine cerebral arteries. AB - For our laboratory's investigation into the role of the endothelial cells in vasospasm following subarachnoid hemorrhage and in inflammatory diseases, we found it necessary to devise a modified method of cell culture, which would be appropriate for studying human endothelial cells from lobectomized brain. We report our techniques to increase cell harvest and ensure reproducibility, our method of culturing endothelial cells from bovine major cerebral arteries, and our morphologic and immunocytochemical characterization of these cells. To increase the harvest of endothelial cells, the blood cells were washed from the lumen of the major cerebral arteries at the slaughterhouse and a modified reversed vessel technique was employed. The monolayer of cultured endothelial cells displayed a cobblestone appearance when it reached confluency and transmission electron microscopy revealed junctional complexes and interdigitation of cytoplasm at Passages 10 and 17. The cells stained positively for Factor VIII-related antigen at Passages 3, 5, 7, 10, and 15. Also the cells metabolized acetylated low-density lipoprotein at Passage 8. To determine the purify of the cultured endothelial cells, an immunocytochemical study of the cytoskeleton was performed on Passage 5 cells using either rhodamine-phalloidin or antibodies against smooth muscle myosin, desmin, and vimentin. PMID- 2318795 TI - Cervical myelopathy: MRI evaluation of cord compression. AB - In order to assess the consequences of cervical spinal cord compression in cervical myelopathy, MRI measurements of the sagittal diameter of the cervical spinal cord were obtained in 50 normal volunteers and 50 patients suffering from cervical myelopathy. Whatever the degree of stenosis, the values obtained in the latter group are significantly inferior to those of the normal control group (average mean diameter: normal group: 8.2 mm; cervical myelopathy: 6.2 mm). PMID- 2318796 TI - Transcatheter arterial embolization in the management of gynaecological bleeding. AB - Transcatheter arterial embolization was attempted in ten patients with gynaecological bleeding. It concerned eight malignant lesions (five cases of spinocellular carcinoma of the uterine cervix, one case of endometrium carcinoma, one case of choriocarcinoma and one case of vulvovaginal metastasis of hypernephroma), and two benign lesions (one uterine arteriovenous malformation and one bleeding after curettage). Bleeding could be stopped in six patients and considerably reduced in two. In two patients selective catheterization of the uterine artery was impossible due to atherosclerotic tortuosity in one and tumoral invasion in the other. PMID- 2318797 TI - Loose bodies of the temporomandibular joint: arthrographic and CT findings in five patients. AB - We report a series of five patients with symptoms of internal derangements of the temporomandibular joint (TMJ), in whom intraarticular loose bodies were found. Three patients with a single loose body had osteochondrosis dissecans of the temporal part of the joint; one trauma patient had two loose bodies (including a bony and a meniscal fragment). The fifth patient presented with a loose meniscal fragment and a complete meniscal rupture, complicating a long-lasting TMJ dysfunction due to non-reducible anterior meniscus displacement. The diagnosis was made by arthrotomography (3 cases), CT (one case) and by CT and arthrotomography (one case). Surgical confirmation was obtained in all patients. Arthrography and CT are accurate in diagnosing TMJ loose bodies; characteristic findings disclosed in both examinations are described. PMID- 2318798 TI - Pre-operative radiological diagnosis of acute necrotizing enteritis in systemic lupus erythematodes. AB - Acute abdominal complications of systemic lupus erythematodes requiring laparatomy are not frequent. A 30-year-old man with systemic lupus erythematodes developed a necrotizing enteritis of the small bowel with pneumatosis intestinalis. Only one case of intestinal vasculitis associated with systemic lupus erythematodes has previously been reported. Presence of intramural gas in the small bowel and of gas in the portal vein was detected on plain abdominal film and confirmed by subsequent CT examination. Since corticosteroids often mask the severity of the disease, radiological evaluation is essential to the overall management of the patient with intestinal vasculitis. Due to the observed radiological signs, emergency laparotomy was performed. Histologic examination revealed necrotizing enteritis due to vasculitis. PMID- 2318799 TI - Multifocal intracranial tumoral lesions: neuroimaging and differential diagnosis with non-oncologic pathology. AB - A variety of intracranial tumours other than metastases may present as multiple lesions. The differentiation between them can mostly be made on their clinical signs and CT-MRI appearance. Nevertheless biopsy must be performed if the space occupying lesions remain unclassifiable. PMID- 2318800 TI - Binding-protein-dependent lactose transport in Agrobacterium radiobacter. AB - Agrobacterium radiobacter NCIB 11883 was grown in lactose-limited continuous culture at a dilution rate of 0.045/h. Washed cells transported [14C]lactose and [methyl-14C]beta-D-thiogalactoside, a nonmetabolisable analog of lactose, at similar rates and with similar affinities (Km for transport, less than 1 microM). Transport was inhibited to various extents by the uncoupling agent carbonyl cyanide p-trifluoromethoxyphenylhydrazone, by unlabeled beta-galactosides and D galactose, and by osmotic shock. The accumulation ratio for methyl-beta-D thiogalactoside was greater than or equal to 4,100. An abundant protein (molecular weight, 41,000) was purified from osmotic-shock fluid and shown by equilibrium dialysis to bind lactose and methyl-beta-D-thiogalactoside, the former with very high affinity (binding constant, 0.14 microM). The N-terminal amino acid sequence of this lactose-binding protein exhibited some homology with several other sugar-binding proteins from bacteria. Antiserum raised against the lactose-binding protein did not cross-react with two glucose-binding proteins from A. radiobacter or with extracts of other bacteria grown under lactose limitation. Lactose transport and beta-galactosidase were induced in batch cultures by lactose, melibiose [O-alpha-D-galactoside-(1----6)alpha-D-glucose], and isopropyl-beta-D-thiogalactoside and were subject to catabolite repression by glucose, galactose, and succinate which was not alleviated by cyclic AMP. We conclude that lactose is transported into A. radiobacter via a binding protein dependent active transport system (in contrast to the H+ symport and phosphotransferase systems found in other bacteria) and that the expression of this transport system is closely linked to that of beta-galactosidase. PMID- 2318801 TI - Isolation and characterization of the lipopolysaccharides from Bradyrhizobium japonicum. AB - The lipopolysaccharide (LPS) of Bradyrhizobium japonicum 61A123 was isolated and partially characterized. Phenol-water extraction of strain 61A123 yielded LPS exclusively in the phenol phase. The water phase contained low-molecular-weight glucans and extracellular or capsular polysaccharides. The LPSs from B. japonicum 61A76, 61A135, and 61A101C were also extracted exclusively into the phenol phase. The LPSs from strain USDA 110 and its Nod- mutant HS123 were found in both the phenol and water phases. The LPS from strain 61A123 was further characterized by polyacrylamide gel electrophoresis, composition analysis, and 1H and 13C nuclear magnetic resonance spectroscopy. Analysis of the LPS by polyacrylamide gel electrophoresis showed that it was present in both high- and low-molecular-weight forms (LPS I and LPS II, respectively). Composition analysis was also performed on the isolated lipid A and polysaccharide portions of the LPS, which were purified by mild acid hydrolysis and gel filtration chromatography. The major components of the polysaccharide portion were fucose, fucosamine, glucose, and mannose. The intact LPS had small amounts of 2-keto-3-deoxyoctulosonic acid. Other minor components were quinovosamine, glucosamine, 4-O-methylmannose, heptose, and 2,3-diamino-2,3-dideoxyhexose. The lipid A portion of the LPS contained 2,3-diamino-2,3-dideoxyhexose as the only sugar component. The major fatty acids were beta-hydroxymyristic, lauric, and oleic acids. A long-chain fatty acid, 27-hydroxyoctacosanoic acid, was also present in this lipid A. Separation and analysis of LPS I and LPS II indicated that glucose, mannose, 4-O methylmannose, and small amounts of 2,2-diamino-2,3-dideozyhexose and heptose were components of the core region of the LPS, whereas fucose, fucosmine, mannose, and small amounts of quinovosamine and glucosamine were components of the LPS O-chain region. PMID- 2318802 TI - Osmoregulation of the salt-tolerant yeast Debaryomyces hansenii grown in a chemostat at different salinities. AB - The intracellular solute composition of the salt-tolerant yeast Debaryomyces hansenii was studied in glucose-limited chemostat cultures at different concentrations of NaCl (4 mM, 0.68 M, and 1.35 M). A strong positive correlation between the total intracellular polyol concentration (glycerol and arabinitol) and medium salinity was demonstrated. The intracellular polyol concentration was sufficient to balance about 75% of the osmotic pressure of the medium in cultures with 0.68 and 1.35 M NaCl. The intracellular concentration of K+ and Na+, which at low external salinity gave a considerable contribution to the intracellular water potential, was only slightly enhanced with raised medium salinity. However, the ratio of intracellular K+ to Na+ decreased; but this decrease was less drastic in the cells than in the surrounding medium, i.e., the cells were able to select for K+ in favor of Na+. The turgor pressure, which was estimated on the basis of intracellular solute concentrations, was 2,200 kPa in cultures with 4 mM NaCl and decreased when the external salinity was raised, resulting in a value of about 500 kPa in cultures with 1.35 M NaCl. The maintenance of a positive turgor pressure at high salinity was mainly due to an increased production and accumulation of glycerol. PMID- 2318803 TI - Immunochemical analysis of lipopolysaccharides from free-living and endosymbiotic forms of Rhizobium leguminosarum. AB - Rhizobium leguminosarum B556 and 8002 differ only with respect to carrying symbiotic plasmids with specificity for Pisum or Phaseolus hosts, respectively. Protease-treated samples derived from free-living cultures of both strains revealed a ladder of lipopolysaccharide (LPS-1) bands after periodate-silver staining of sodium dodecyl sulfate-polyacrylamide gels. These bands were arranged as doublets. After Western (immuno-) blotting, all LPS-1 bands reacted with monoclonal antibody JIM 21, whereas monoclonal antibody MAC 57 reacted only with the upper (slower-migrating) band and monoclonal antibody MAC 114 reacted only with the lower band of each doublet pair. Preparations obtained from bacteroids of Pisum or Phaseolus nodules showed significant differences in the size distribution and antigenicity of LPS. In bacteroids from Phaseolus sp., JIM 21 and MAC 57 each stained a ladder of LPS-1 bands on sodium dodecyl sulfate polyacrylamide gels which corresponded in mobility to the upper band of each doublet pair seen in free-living cultures. MAC 114 did not react with the LPS from Phaseolus sp.-derived bacteroids. In bacteroids from Pisum sp., only fast migrating (lower-molecular-weight) forms of LPS-1 could be visualized on gels, but both upper and lower bands of each doublet were still present and could be stained by the appropriate monoclonal antibody, MAC 57 or MAC 114, respectively. Similarly, bacteroids from R. leguminosarum 3841, which nodulates Pisum species, differed with respect to the structure and antigenicity of their LPS-1 from bacteroids of a related strain, B625, which nodulates Phaseolus species. Physiological factors were investigated that could account for these differences between the structures of LPS-1 from free-living cultures of B556 and 8002 and that from bacteroids. The following modifications in growth conditions each tended to reduce the expression of MAC 114 antigen and enhance the expression of MAC 57 antigen: succinate rather than glucose as the carbon source; microaerobic (2.5%, vol/vol) oxygen concentrations; and acidic (pH 5 to 6) culture medium. When all three of these conditions were combined, the LPS-1 that resulted was very similar to that in bacteroids from Pisum nodules. However, it was not possible to reproduce the LPS-1 pattern observed for bacteroids from Phaseolus nodules, which maintained a ladder of LPS bands reacting with MAC 57 antibody. PMID- 2318804 TI - Heat shock response in mycoplasmas, genome-limited organisms. AB - We have measured the effect of heat shock on three mycoplasmas (Acholeplasma laidlawii K2 and JA1 and Mycoplasma capricolum Kid) and demonstrated the induction of mycoplasma heat shock proteins under these conditions. Increased synthesis of at least 5 heat shock proteins in A. laidlawii K2, 11 heat shock proteins in A. laidlawii JA1, and 7 heat shock proteins in M. capricolum was observed by electrophoretic analysis of proteins from heat-shocked cells in sodium dodecyl sulfate-polyacrylamide gels. In all three strains, major heat shock proteins (66 to 68 and 26 to 29 kilodaltons [kDa]) were found. The 66- to 68-kDa protein cross-reacted with antibody to Escherichia coli DnaK protein, suggesting that this heat shock protein has been conserved in spite of major reductions in genetic complexity during mycoplasma evolution. A. laidlawii also contained a 60-kDa protein that cross-reacted with eubacterial GroEL protein and a 40-kDa protein that cross-reacted with E. coli RecA protein. Unlike with coliphages, the mycoplasma virus L2 progeny yield was not increased when virus was plated on heat-shocked A. laidlawii host cells. However, UV-irradiated L2 virus could be host cell reactivated by both A. laidlawii SOS repair and heat shock systems. PMID- 2318805 TI - Genomic organization and expression of Campylobacter flagellin genes. AB - Campylobacter coli VC167, which undergoes an antigenic flagellar variation, contains two full-length flagellin genes, flaA and flaB, that are located adjacent to one another in a tandem orientation and are 91.5% homologous. The gene product of flaB, which has an Mr of 58,946, has 93% sequence homology to the gene product of flaA, which has an Mr of 58,916 (S. M. Logan, T. J. Trust, and P. Guerry, J. Bacteriol. 171:3031-3038, 1989). Mutational analyses and primer extension experiments indicated that the two genes are transcribed under the control of distinct promoters but that they are expressed concomitantly in the same cell, regardless of the antigenic phase of flagella being produced. The flaA gene, which was expressed at higher levels than the flaB gene in both phases, was transcribed from a typical sigma 28-type promoter, whereas the flaB promoter was unusual. A mutant producing only the flaB gene product did not synthesize a flagellar filament and was nonmotile. Southern blot analysis indicated that flagellar antigenic variation involves a rearrangement of flagellin sequence information rather than the alternate expression of the two distinct genes. PMID- 2318806 TI - Efficiency factors and ATP/ADP ratios in nitrogen-fixing Bacillus polymyxa and Bacillus azotofixans. AB - The efficiency factor, the number of moles of ATP generated per mole of glucose fermented, was determined in anaerobic, non-carbon-limited N2-fixing cultures of Bacillus polymyxa, Bacillus macerans, Bacillus azotofixans, and Clostridium butyricum through identification and quantitation of the fermentation products by 13C nuclear magnetic resonance spectroscopy and measurement of acetate kinase activities. All three Bacillus species had acetate kinase activities and produced acetate and ethanol as the major fermentation products. The maximum amounts of ATP generated per mole of glucose fermented were 2.70, 2.64, and 2.88 mol in B. polymyxa, B. macerans, and B. azotofixans, respectively, compared with 3.25 mol in C. butyricum. Thus, in the N2-fixing Bacillus species, the efficiency factors are lower than that in C. butyricum. Steady-state ATP/ADP concentration ratios were measured in non-carbon-limited N2-fixing cultures of B. polymyxa and B. azotofixans through separation and quantitation of the adenylates in cell extracts by ion-pair reversed-phase high-performance liquid chromatography. The observed ATP/ADP ratios were 4.5 and 3.8, and estimated energy charges were 0.81 to 0.86 and 0.81 to 0.83, respectively, for B. polymyxa and B. azotofixans. The results suggest that under these growth conditions, the rate of ATP regeneration is adequate to meet the energy requirement for N2 fixation in the Bacillus species, in contrast to N2-fixing Clostridium pasteurianum and Klebsiella pneumoniae, for which substantially lower steady-state ATP/ADP ratios and energy charges have been reported. Implications of the results are discussed in relation to possible differences between Bacillus and Clostridium species in energy requirements for N2 fixation and concomitant ammonia assimilation. PMID- 2318807 TI - Effect of temperature shifts on gliding motility, adhesion, and fatty acid composition of Cytophaga sp. strain U67. AB - Gliding motility and flipping of 25 degrees C-adapted Cytophaga sp. strain U67 were inhibited when the bacteria were shifted to a less than or equal to 12 degrees C environment; motility was not blocked by a shift to 13 degrees C. Bacteria adapted to 4 degrees C were motile over the entire 4 to 25 degrees C temperature range tested. U67 adhesion to the substratum appeared to be unaffected by temperature shifts. Bacteria adapted to 4 degrees C had higher proportions of unsaturated and branched-chain fatty acids than did those grown at 25 degrees C. When 25 degrees C-adapted bacteria were subjected to a gradual temperature decline, the time of reappearance of gliding competence at 4 to 5 degrees C was correlated with these changes in fatty acid composition. PMID- 2318808 TI - Manganese(II) induces cell division and increases in superoxide dismutase and catalase activities in an aging deinococcal culture. AB - Addition of Mn(II) at 2.5 microM or higher to stationary-phase cultures of Deinococcus radiodurans IR was found to trigger at least three rounds of cell division. This Mn(II)-induced cell division (Mn-CD) did not occur when the culture was in the exponential or death phase. The Mn-CD effect produced daughter cells proportionally reduced in size, pigmentation, and radioresistance but proportionally increased in activity and amount of the oxygen toxicity defense enzymes superoxide dismutase and catalase. In addition, the concentration of an Mn-CD-induced protein was found to remain high throughout the entire Mn-CD phase. It was also found that an untreated culture exhibited a growth curve characterized by a very rapid exponential-stationary transition and that cells which had just reached the early stationary phase were synchronous. Our results suggest the presence of an Mn(II)-sensitive mechanism for controlling cell division. The Mn-CD effect appears to be specific to the cation Mn(II) and the radioresistant bacteria, deinococci. PMID- 2318809 TI - Purification of NADPH-dependent electron-transferring flavoproteins and N terminal protein sequence data of dihydrolipoamide dehydrogenases from anaerobic, glycine-utilizing bacteria. AB - Three electron-transferring flavoproteins were purified to homogeneity from anaerobic, amino acid-utilizing bacteria (bacterium W6, Clostridium sporogenes, and Clostridium sticklandii), characterized, and compared with the dihydrolipoamide dehydrogenase of Eubacterium acidaminophilum. All the proteins were found to be dimers consisting of two identical subunits with a subunit Mr of about 35,000 and to contain about 1 mol of flavin adenine dinucleotide per subunit. Spectra of the oxidized proteins exhibited characteristic absorption of flavoproteins, and the reduced proteins showed an A580 indicating a neutral semiquinone. Many artificial electron acceptors, including methyl viologen, could be used with NADPH as the electron donor but not with NADH. Unlike the enzyme of E. acidaminophilum, which exhibited by itself a dihydrolipoamide dehydrogenase activity (W. Freudenberg, D. Dietrichs, H. Lebertz, and J. R. Andreesen, J. Bacteriol. 171:1346-1354, 1989), the electron-transferring flavoprotein purified from bacterium W6 reacted with lipoamide only under certain assay conditions, whereas the proteins of C. sporogenes and C. sticklandii exhibited no dihydrolipoamide dehydrogenase activity. The three homogeneous electron transferring flavoproteins were very similar in their structural and biochemical properties to the dihydrolipoamide dehydrogenase of E. acidaminophilum and exhibited cross-reaction with antibodies raised against the latter enzyme. N terminal sequence analysis demonstrated a high degree of homology between the dihydrolipoamide dehydrogenase of E. acidaminophilum and the electron transferring flavoprotein of C. sporogenes to the thioredoxin reductase of Escherichia coli. Unlike these proteins, the dihydrolipoamide dehydrogenases purified from the anaerobic, glycine-utilizing bacteria Peptostreptococcus glycinophilus, Clostridium cylindrosporum, and C. sporogenes exhibited a high homology to dihydrolipoamide dehydrogenases known from other organisms. PMID- 2318810 TI - A Caulobacter gene involved in polar morphogenesis. AB - At specific times in the cell cycle, the bacterium Caulobacter crescentus assembles two major polar organelles, the flagellum and the stalk. Previous studies have shown that flbT mutants overproduce flagellins and are unable to form chemotaxis swarm rings. In this paper, we report alterations in both the stalk and the flagellar structure that result from a mutation in the flagellar gene flbT. Mutant strains produce some stalks that have a flagellum, produce some stalks that have an extra lobe protruding from their sides, have filaments lacking the 29-kilodalton flagellin, and produce several unusual cell types, including filamentous cells as well as predivisional cells with two stalks and predivisional cells with no stalk at all. We propose that flagellated stalks arise as a consequence of a failure to eject the flagellum at the correct time in the cell cycle and that the extra stalk lobe is due to a second site for the initiation of stalk biogenesis. Thus, a step in the pathway that establishes the characteristic asymmetry of the C. crescentus cell appears to be disrupted in flbT mutants. We have also identified a new structural feature at the flagellated pole and the tip of the stalk: the 10-nm polar particle. The polar particles appear as a cluster of approximately 1 to 10 stain-excluding rings, visible in electron micrographs of negatively stained wild-type cells. This structure is absent at the flagellar pole but not in the stalks of flbT mutant predivisional cells. PMID- 2318811 TI - Parasporal bodies of Bacillus laterosporus sporangia. AB - Intact colonies of Bacillus laterosporus examined by thin-section transmission electron microscopy revealed sporangia in various stages of development and degeneration as the endospores matured. The sporangia formed a surface layer of hexagonally arranged subunits. The variety of parasporal bodies raised questions of developmental and ecologic utility. PMID- 2318812 TI - Osmosensitivity phenotypes of Agrobacterium tumefaciens mutants that lack periplasmic beta-1,2-glucan. AB - The periplasmic cyclic beta-1,2-glucan of Agrobacterium tumefaciens is believed to maintain high osmolarity in the periplasm during growth of the bacteria on low osmotic-strength media. Strains with mutations in the chvA or chvB gene do not accumulate beta-1,2-glucan in their periplasm and exhibit pleiotropic phenotypes, including inability to form crown gall tumors on plants. We examined the effects of medium osmolarity to determine whether some or all of these phenotypes result from suboptimal periplasmic osmolarity. The mutants grew more slowly than wild type cells and exhibited altered periplasmic and cytoplasmic protein content when cultured in low-osmotic-strength media, but not when cultured in high-osmotic strength media. These observations support a role for periplasmic glucan in osmoadaptation. However, the mutants were avirulent and exhibited reduced motility regardless of the osmolarity of the medium. Therefore, beta-1,2-glucan may play roles in virulence and motility that are unrelated to its role in osmoadaptation. PMID- 2318813 TI - Virulence genes promote conjugative transfer of the Ti plasmid between Agrobacterium strains. AB - Certain virulence region operons of the Agrobacterium tumefaciens Ti plasmid promoted conjugative Ti plasmid transfer. Mutations in the vir region of pTiC58 inhibited conjugative plasmid transfer between A. tumefaciens strains. Mutations in virA, virG, 5' virB, and virE had the greatest effect on plasmid transfer, and mutations in virC had no effect. Transfer inhibition in vir mutants occurred in the presence or absence of acetosyringone. PMID- 2318814 TI - A three-dimensional model of the pelvic floor and anorectal anatomy. AB - The large number of individuals suffering from anorectal dysfunctions necessitates a better understanding of the anatomy and physiology of that region. A three-dimensional model which realistically simulates the pelvic floor and anorectal region was commissioned to supplement traditional forms of instruction for medical students and residents. This paper discusses the need for and development of a life-sized and anatomically accurate prototype model appropriate for teaching and research. PMID- 2318815 TI - Cap binding protein complex that restores protein synthesis in heat-shocked Ehrlich cell lysates contains highly phosphorylated eIF-4E. AB - Cell-free protein-synthesizing systems derived from Ehrlich ascites tumor cells that have been exposed to elevated temperatures retain the inhibition of translation that is seen at the cellular level. A multisubunit cap binding protein complex able to restore protein synthesis in these cell free systems was purified from Ehrlich ascites tumor cells via affinity chromatography using m7GTP Sepharose and fast protein liquid chromatography on Mono Q. The purified complex contains an Mr 220,000 polypeptide (p220) and an Mr 28,000 polypeptide (p28), both of which are components of eukaryotic initiation factor 4F (eIF-4F). p28 is identical to eIF-4E. Restoring activity was relatively free of the Mr 46,000 polypeptide (p46) that is the third component of eIF-4F and does not appear to be dependent on its presence. p28 associated in a complex with p220 is 85% phosphorylated; however, the majority of p28 is not associated with p220, and this free form is only about 50% phosphorylated. The correlation between association of p28 with p220 and high levels of p28 phosphorylation suggests a possible role for phosphorylation in association of p220 with p28. PMID- 2318816 TI - Nonrandom induction of pyrimidine-pyrimidone (6-4) photoproducts in ultraviolet irradiated human chromatin. AB - Radioimmunoassays that detect pyrimidine-pyrimidone (6-4) photoproducts and cyclobutane dimers were used to determine the relative induction of these photoproducts in nucleosomal (core) and internucleosomal (linker) DNA in human cell chromatin irradiated with UV light. Cyclobutane dimers were formed in equal amounts/nucleotide in core and linker DNA, whereas (6-4) photoproducts occurred with 6-fold greater frequency/nucleotide in linker DNA. PMID- 2318817 TI - Expression of the hepatocyte Na+/bile acid cotransporter in Xenopus laevis oocytes. AB - The expression of the basolateral Na+/bile acid (taurocholate) cotransport system of rat hepatocytes has been studied in Xenopus laevis oocytes. Injection of rat liver poly(A)+ RNA into the oocytes resulted in the functional expression of Na+ gradient stimulated taurocholate uptake within 3-5 days. This Na(+)-dependent portion of taurocholate uptake exhibited saturation kinetics (apparent Km approximately 91 microM) and could be inhibited by 4,4'-diisothiocyano-2,2' disulfonic acid stilbene. Furthermore, the expressed taurocholate transport activity demonstrated similar substrate inhibition and stimulation by low concentrations of bovine serum albumin as the basolateral Na+/bile acid cotransport system previously characterized in intact liver, isolated hepatocytes, and isolated plasma membrane vesicles. Finally, a 1.5- to 3.0 kilobase size-class of mRNA could be identified that was sufficient to express the basolateral Na+/taurocholate uptake system in oocytes. These results demonstrate that "expression cloning" represents a promising approach to ultimately clone the gene and to further characterize the molecular properties of this important hepatocellular membrane transport system. PMID- 2318818 TI - Mutagenesis of a single hydrogen bond in cytochrome P-450 alters cation binding and heme solvation. AB - Cytochrome P-450cam, a monoxygenase responsible for the regiospecific hydroxylation of camphor, binds its substrate through complimentary van der Waals contacts and the formation of a single hydrogen bond between tyrosine 96 and the ketone group of camphor. Substrate association is positively regulated through the binding of a monovalent cation and the oxidation-reduction potential modulated by the spin state of the ferric heme controlled by water access to the sixth coordination site of the iron. Removal of this single hydrogen bond via site-directed mutagenesis of tyrosine 96 to phenylalanine 96 defines this aspect of the protein structure as responsible for the linkage between cation and substrate cooperativities, the degree of spin state conversion resulting from water access via macromolecule and substrate dynamics, and suggests a specific location for the cation binding site. PMID- 2318819 TI - A specific enhancing effect of N,N-dimethylsphingosine on epidermal growth factor receptor autophosphorylation. Demonstration of its endogenous occurrence (and the virtual absence of unsubstituted sphingosine) in human epidermoid carcinoma A431 cells. AB - Our previous study suggested that N,N-dimethylsphingosine, but not unsubstituted sphingosine, could be a modulator of protein kinase C in epidermoid carcinoma A431 cells, since N,N-dimethyl-D-erythrosphingenine showed a stronger stereospecific effect on protein kinase C activity in comparison with N,N dimethyl-L-erythrosphingenine, unsubstituted D- or L-erythrosphingenine, and gangliosides (Igarashi, Y., Hakomori, S., Toyokuni, T., Dean, B., Fujita, S., Sugimoto, M., Ogawa, T., El-Ghendy, K., and Racker, E. (1989) Biochemistry 28, 6796-6800). Other studies also indicated that commercial sphingosine preparation has an enhancing effect on epidermal growth factor (EGF) receptor kinase activity in A431 cells (Davis, R. J., Girones, N., and Faucher, M. F. (1988) J. Biol. Chem. 263, 5373-5379; Faucher, M. F., Girones, N., Hannun, Y. A., Bell, R. M., and Davis, R. J. (1988) J. Biol. Chem. 263, 5319-5327). In the present paper, we report (i) the effect of N,N-dimethylsphingosine as compared with lyso glycosphingolipids and other sphingolipid breakdown products on EGF receptor autophosphorylation and (ii) demonstration of endogenous N,N-dimethylsphingosine synthesis and the virtual absence of unsubstituted sphingosine in A431 cells. The autophosphorylation of EGF receptor in the absence of detergent was strongly enhanced by N,N-dimethyl-D-erythrosphingenine; this effect was even obvious in the absence of EGF and synergistic in the presence of EGF. Similar enhancing activity was not produced by N,N-dimethyl-L-erythrosphingenine, D- and L erythrosphingenine, N-monomethyl-D-erythrosphingenine, N-acetyl-D erythrosphingenine, or the five lyso-glycosphingolipids tested. Labeling of sphingosine in A431 cells by culturing in medium containing [3H]Ser for various durations, followed by extraction and isolation of sphingolipids by standard procedures, resulted in clear bands corresponding to N,N-dimethylsphingosine and ceramide, whereas the band corresponding to sphingosine was virtually absent. The bands corresponding to N,N-dimethylsphingosine and ceramide intensified when cells were treated with metabolic inhibitor for UDP-Glc:Cer beta-Glc transferase (which causes accumulation of ceramide). These results indicate that N,N dimethylsphingosine acts as a stereospecific enhancer for EGF receptor kinase and is able to produce EGF-like activity in vitro even in the absence of EGF and detergent. Under physiological conditions, N,N-dimethylsphingosine is the major catabolite resulting from ceramide breakdown. PMID- 2318820 TI - Regulation of parathyroid hormone-related peptide gene expression by cycloheximide. AB - A novel parathyroid hormone-related peptide (PTHRP) has been isolated from tumors associated with the syndrome of humoral hypercalcemia of malignancy. The human PTHRP gene appears to use multiple promoters and contains alternatively spliced 3' exons which give rise to three PTHRP mRNA classes, each bearing multiple copies of an AU motif that has been associated with mRNA instability. We report here that inhibition of protein synthesis leads to the super-induction of PTHRP mRNA expression in a number of human and rat cell lines. This phenomenon was found to reflect both an increase in the rate of PTHRP gene transcription and a stabilization of PTHRP mRNAs. The transcriptional mechanism appears to preferentially involve the activity of a short downstream promoter of the gene, which is presumed to be regulated by a labile repressor protein. Our findings indicate that both transcriptional and posttranscriptional mechanisms may be important control points in the regulation of PTHRP expression in normal and malignant cells. PMID- 2318821 TI - In vitro expression and site-specific mutagenesis of the cloned human lipoprotein lipase gene. Potential N-linked glycosylation site asparagine 43 is important for both enzyme activity and secretion. AB - Detailed structure-function information about human lipoprotein lipase (LPL) is unavailable because it is difficult to purify large amounts of the enzyme for study. To circumvent this problem, we constructed an in vitro LPL expression vector. Human LPL cDNA was cloned and inserted into the expression vector p91023(B). After transfection of COS M-6 cells with the human LPL cDNA construct, LPL enzyme activity was detected in cell extracts and culture medium. Purified human apolipoprotein C-II caused a 5-fold stimulation of the recombinant human LPL expressed in vitro. Using site-specific mutagenesis, Ala residues were substituted for Asn residues at two potential N-linked glycosylation sites (positions 43 and 359) and at a third unrelated Asn (position 257) in the LPL cDNA. RNA blot analysis demonstrated the presence of a single mRNA species in COS cells transfected with wild-type and mutant LPL expression vectors. Intracellular and secreted LPL activity was absent in the construct containing an Ala for Asn mutation at position 43, whereas the same substitutions at positions 257 and 359 did not appreciably affect activity. LPL activity was also absent in another construct containing a Gln for Asn mutation at position 43. Quantitation of LPL protein mass concomitant with measurement of enzyme activity showed that substitution of Ala or Gln for Asn at position 43 resulted in the production of an enzymatically inactive protein which accumulated intracellularly but was not secreted into the culture medium. Our report represents an initial documentation of the expression of cloned human LPL in vitro and of the importance of Asn-43 for both enzyme activity and secretion. PMID- 2318822 TI - Glomerular basement membrane. Identification of a fourth chain, alpha 4, of type IV collagen. AB - The noncollagenous domain hexamer of collagen IV from bovine glomerular basement membrane was further investigated to determine the types of collagen chain from which subunits M2*b and M3 are derived. M2*b was shown to be a shorter form, containing 9 fewer residues, of M2*a which was previously established as the noncollagenous domain of a third chain, alpha 3, of collagen IV (Saus, J., Wieslander, J., Langeveld, J.P.M., Quinones, S., and Hudson, B.G. (1988) J. Biol. Chem. 263, 13374-13380). M3 was identified as the noncollagenous domain of a fourth chain, alpha 4, of type IV collagen, on the basis of additional sequence data together with previous findings. A comparison of the collagenous noncollagenous junction regions of alpha 3(IV) and alpha 4(IV) chains with those of classical alpha 1(IV) and alpha 2(IV) chains reveals structural information which provides a potential strategy for molecular cloning of these novel chains. The results further reveal the complexity of electrophoresis patterns of the hexamer and potential ambiguities in using one-dimensional patterns to determine whether molecular defects of collagen IV occur in pathological processes affecting basement membranes. PMID- 2318823 TI - 8-Azido double-stranded RNA photoaffinity probes. Enzymatic synthesis, characterization, and biological properties of poly(I,8-azidoI).poly(C) and poly(I,8-azidoI).poly(C12U) with 2',5'-oligoadenylate synthetase and protein kinase. AB - The technique of photoaffinity labeling has been applied to the double-stranded RNA (dsRNA)-dependent enzyme 2',5'-oligoadenylate (2-5A) synthetase to provide a means for the examination of RNA-protein interaction(s) in the dsRNA allosteric binding domain of this enzyme. The synthesis, characterization, and biological properties of the photoaffinity probe poly[( 32P]I,8-azidoI).poly(C) and its mismatched analog poly[( 32P]I,8-azidoI).poly(C12U), which mimic the parent molecules poly(I).poly(C) and poly(I).poly(C12U), are described. The efficacy of poly[( 32P]I,8-azidoI).poly(C) and poly[( 32P]I,8-azidoI).poly(C12U) as allosteric site-directed activators is demonstrated using highly purified 2-5A synthetase from rabbit reticulocyte lysates and from extracts of interferon treated HeLa cells. The dsRNA photoprobes activate these two 2-5A synthetases. Saturation of 2-5A synthetase is observed at 6 x 10(-4) g/ml poly[( 32P]I,8 azidoI).poly(C) following photolysis for 20 s at 0 degrees C. The photoincorporation of poly[( 32P]I,8-azidoI).poly(C) is specific, as demonstrated by the prevention of photoincorporation by native poly(I).poly(C). DNA, poly(I), and poly(C) are not competitors of poly[( 32P]I,8-azidoI).poly(C). Following UV irradiation of 2-5A synthetase with poly[( 32P]I,8-azidoI).poly(C), the reaction mixture is treated with micrococcal nuclease to hydrolyze azido dsRNA that is not cross-linked to the enzyme. A radioactive band of 110 kDa (the same as that reported for native rabbit reticulocyte lysate 2-5A synthetase) is observed following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The specific photolabeling of the 2-5A synthetase suggests that the azido dsRNA is intrinsic to the allosteric binding domain. The utility of poly[( 32P]I,8-azidoI).poly(C) for the detection of dsRNA-dependent binding proteins and the isolation of peptides at or near the allosteric binding site is discussed. PMID- 2318824 TI - The efflux of lysosomal cholesterol from cells. AB - To gain insight into the transport of sterol from lysosomes to the plasma membrane, we studied the efflux of lysosomal free cholesterol from intact Fu5AH rat hepatoma cells to high density lipoprotein (HDL) and other extracellular acceptors that promote sterol desorption from the plasma membrane. The procedures involved pulsing cells at 15 degrees C with low density lipoprotein that had been reconstituted with [3H]cholesteryl oleate and then incubating the cells at 37 degrees C in the presence of a sterol acceptor, while monitoring both the hydrolysis of [3H]cholesteryl oleate in lysosomes and the efflux of the resulting [3H]free cholesterol to the acceptor. After warming cells to 37 degrees C, rapid hydrolysis of [3H]cholesteryl oleate began after 10-20 min, and the lysosomally generated [3H]free cholesterol became available for efflux after an additional delay of 40-50 min. The kinetics of hydrolysis and the delay between hydrolysis and efflux were unchanged over a wide range of HDL3 concentrations (10-1000 micrograms of protein/ml), and with acceptors that do not interact with HDL specific cell surface binding sites (phospholipid vesicles, dimethyl suberimidate cross-linked HDL). In addition, the delivery of lysosomal cholesterol to the plasma membrane was unaffected when cellular cholesterol content was elevated 2.6 fold above the normal control level, or when the activity of cellular acyl coenzyme A/cholesterol acyltransferase (ACAT) was stimulated with exogenous oleic acid. We conclude that in the Fu5AH cell, a maximum of 40-50 min is required for the transport of cholesterol from lysosomes to the plasma membrane and that this transport is not regulated in response to either specific extracellular acceptors or the content of sterol in cells. The lack of effect of increased ACAT activity implies that the pathway for this transport does not involve passage of sterol through the rough endoplasmic reticulum, the subcellular location of ACAT. PMID- 2318825 TI - Episialin, a carcinoma-associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini. AB - Episialin is a mucin-type glycoprotein present at the luminal side of most glandular epithelial cells. We have isolated cDNA clones encoding episialin and determined the structure of the gene. The gene encodes a transmembrane protein which consists of, for the greater part, tandem repeats of 20 amino acids. The number of these repeats varies between 40 and 90 among different alleles. The repeats and most of the remainder of the protein are very rich in potential O linked glycosylation sites. Two different splice variants were found. Interestingly, the proteins encoded by these two variants differ in their signal sequences and in the extreme amino-terminal parts of the mature proteins, suggesting alternative processing of these two species. PMID- 2318826 TI - Chiral and structural discrimination in binding of polypeptides with condensed nucleic acid structures. AB - In biological systems nucleic acids are invariably found in highly compact forms. These rather intricate forms raise questions of basic importance which are related to the various factors involved in the condensation processes, the chemical, physical, and structural features revealed by the packed species, and the effects of the extremely tight packaging upon interactions of the DNA molecules with proteins and drugs. A means for addressing these questions on a molecular level is provided by various procedures known to induce in vitro condensation of DNA molecules into highly compact species which, in turn, may serve as a model for the in vivo physical organization of nucleic acids. A study of the optical properties of the tightly packed DNA molecules indicates that the interactions of these species with polypeptides are characterized by distinct, hitherto unobserved, chiral and structural discrimination. Specifically, the polypeptides found to be selected against are composed of those amino acids that are not normally used in protein biosynthesis, such as D-lysine or ornithine. These findings provide new clues to long debated topics such as the specific universal chirality of amino acids in proteins or the correlation between conformational flexibility of polypeptides and their ability to form stable compact complexes with nucleic acids. PMID- 2318827 TI - Characteristics of the histamine-sensitive calcium store in vascular smooth muscle. Comparison with norepinephrine- or caffeine-sensitive stores. AB - Using the microfluorometry of an intracellularly trapped calcium indicator dye, quin2, characteristics of intracellular Ca2+ store sites sensitive to histamine, norepinephrine, or caffeine were investigated using rat vascular smooth muscle cells in primary culture at 25 degrees C. With similar time courses, both histamine- and the norepinephrine-sensitive Ca2+ store sites were readily depleted in Ca2(+)-free medium and almost completely replenished by loading the cells with 1.0 mM Ca2+ solution for 3 min, while the caffeine-sensitive Ca2+ store site was little affected. In the absence of extracellular Ca2+, transient elevations of cytosolic Ca2+ repeatedly appeared in response to repetitive applications of histamine, norepinephrine, or caffeine, with progressive reductions in peak levels. Histamine released Ca2+ from the norepinephrine sensitive store site and norepinephrine released Ca2+ from the histamine sensitive one. On the other hand, caffeine had little effect on the histamine- and/or the norepinephrine-sensitive Ca2+ store site in Ca2(+)-free medium, and vice versa. We propose that the location and mechanisms of release of Ca2+ of the histamine-sensitive Ca2+ store site are identical with events at the norepinephrine-sensitive site, and differ from the caffeine-sensitive one, in vascular smooth muscle cells in primary culture. PMID- 2318828 TI - Dexamethasone negatively regulates phenobarbitone-activated transcription but synergistically enhances cytoplasmic levels of cytochrome P-450b/e messenger RNA. AB - Dexamethasone has a potentiating effect on phenobarbitone mediated induction of cytochrome P-450b + e mRNAs in adult rat liver. However, the glucocorticoid inhibits phenobarbitone-activated transcription of cytochrome P-450b + e mRNAs by 60-70%. This inhibitory effect is evident in run-off transcription of the endogenous genes as well as in the transcription of an added cloned gene fragment. Dexamethasone inhibits the phenobarbitone-mediated increase in the binding of a transcription factor(s) to the upstream region of the gene as evidenced by gel retardation and Southwestern blot analysis. The glucocorticoid does not stabilize the phenobarbitone-induced polyribosomal cytochrome P-450b + e mRNAs but appears to stabilize the nuclear transcripts. It is proposed that a negative element may mediate the action of dexamethasone at the level of nuclear transcription and stabilization of the nuclear transcript may account for the potentiating effect of the glucocorticoid on phenobarbitone-mediated increase in cytochrome P-450b + e mRNAs in the cytoplasm of the adult rat liver. However, the cytochrome P-450b protein levels are slightly lower in phenobarbitone + dexamethasone treatment than in phenobarbitone-treated liver microsomes. PMID- 2318829 TI - Use of isotope effects to characterize intermediates in mechanism-based inactivation of dopamine beta-monooxygenase by beta-chlorophenethylamine. AB - A mechanism for beta-chlorophenethylamine inhibition of dopamine beta monooxygenase has been postulated in which bound alpha-aminoacetophenone is generated followed by an intramolecular redox reaction to yield a ketone-derived radical cation as the inhibitory species (Mangold, J.B., and Klinman, J.P. (1984) J. Biol. Chem. 259, 7772-7779). Based on the assumption that the ketone radical is the inhibitory intermediate, an analogous system was predicted and verified (Bossard, M.J., and Klinman, J.P. (1986) J. Biol. Chem. 261, 16421-16427). In the present study, the role of alpha-aminoacetophenone as the proposed intermediate in the inactivation by beta-chlorophenethylamine was examined in greater detail. From the interdependence of tyramine and alpha-aminoacetophenone concentrations, ketone inactivation is concluded to occur at the substrate site as opposed to potential binding at the reductant-binding site. Using beta-[2-1H]- and beta-[2 2H]chlorophenethylamine, the magnitude of the deuterium isotope effect on inactivation under second-order conditions has been found to be identical to that observed under catalytic turnover, D(kappa inact/Ki) = D(kappa cat/Km) = 6-7. By contrast, the isotope effect on inactivation under conditions of substrate and oxygen saturation, D kappa inact = 2, is 3-fold smaller than that seen on catalytic turnover, D kappa cat = 6. This reduced isotope effect for inactivation is attributed to a normal isotope effect on substrate hydroxylation followed by an inverse isotope effect on the partitioning of the enol of alpha aminoacetophenone between oxidation to a radical cation versus protonation to regenerate ketone. These findings are unusual in that two isotopically sensitive steps are present in the inactivation pathway whereas only one is observable in turnover. PMID- 2318830 TI - Regulation and ligand-binding specificities of two sex-specific bile acid-binding proteins of rat liver cytosol. AB - Rat liver cytosolic proteins were photoaffinity labeled with the synthetic steroid [3H]methyltrienolone in order to identify and characterize hepatic proteins that may participate in the intracellular binding and transport of steroid hormones and other sterols. A male-specific and a female-specific sterol binding protein (SBP) that migrated to the 4 S region of a sucrose gradient and had similar molecular weights (male-specific 34-kDa protein (SBP34), female specific 31-kDa protein (SBP31] were thus identified. Experiments were undertaken to determine the biochemical basis for the sex-specific expression of these two proteins. In vivo hormonal manipulations established that the female-specific expression of SBP31 could, in part, be accounted for by the suppressive effects of androgen on SBP31 levels in male rats. In contrast, androgen stimulated expression of the male-specific SBP34, while estrogen and the estrogen-regulated continuous plasma growth hormone profile that is characteristic of adult female rats were suppressive toward this protein. Unlike several other androgen dependent hepatic proteins, however, SBP34 did not require an intact pituitary for androgen-stimulated expression, nor was its expression stimulated by the intermittent pulses of plasma growth hormone that are characteristic of adult male rats. SBP34 and SBP31 were not induced but were suppressed to various extents by dexamethasone, phenobarbital, and clofibrate, drugs that are known to induce other hepatic proteins involved in steroid binding and metabolism. Competition experiments revealed that SBP31 has a relatively broad ligand specificity, with significant competition for [3H]methyltrienolone binding exhibited by bile acids (chenodeoxycholic acid and lithocholic acid) and a range of steroid hormones (progesterone, estradiol, testosterone, and 5 alpha dihydrotestosterone) when present in the low micromolar range. No binding was detected with this protein toward cholesterol, triamcinolone acetonide, 5 alpha androstan-3 alpha,17 beta-diol, cholic acid, and deoxycholic acid. In contrast, SBP34 exhibited greater binding specificity, with competition for [3H]methyltrienolone binding observed only with primary bile acids (cholic acid and chenodeoxycholic acid) and their metabolites (deoxycholic acid and lithocholic acid). On the basis of these binding specificities and the relatively high concentration of bile acids found in the liver, it is proposed that SBP31 and SBP34 function in the intracellular binding and/or transport of bile acids. PMID- 2318832 TI - Effect of methionine oxidation and deletion of amino-terminal residues on the conformation of parathyroid hormone. Circular dichroism studies. AB - Circular dichroism (CD) studies of parathyroid hormone (PTH), its oxidized forms, and some fragments of the hormone are described. The CD spectrum of native PTH (84 amino acids) and the active fragment, 1-34 PTH, suggests that most of the secondary structure resides in the amino-terminal segment of this hormone. Oxidation of the methionine residue at position 18 has a small impact on secondary structure, whereas oxidation of the methionine at position 8 produces substantial changes. Oxidation of both methionines produces secondary structure changes that are greater than the sum of those seen upon oxidation of the individual methionines. The CD spectrum for the 3-34 fragment of PTH is identical to that of the 1-34 fragment, and that of the 7-34 fragment is only slightly different. The spectra of the 13-34 and 19-34 fragments are markedly altered from that of the 1-34 peptide, and those of the 9-84 and 19-84 fragments of native PTH are significantly different from the intact hormone. Computer-assisted estimates of secondary structure content, and difference spectra, were utilized to evaluate the secondary structure content of the peptides. These results suggest that residues 6-12 are important in formation of helical secondary structure and that a reverse turn may be important for the folding of PTH into a conformation with high affinity for receptors. Residues 1 and 2 appear to make no contribution to the secondary structure and may be directly involved in activation of receptors. PMID- 2318831 TI - The carboxyl-terminal region of thioesterase II participates in the interaction with fatty acid synthase. Use of electrospray ionization mass spectrometry to identify a carboxyl-terminally truncated form of the enzyme. AB - Medium-chain S-acyl fatty acid synthase thioester hydrolase (thioesterase II), a discrete 263-residue serine active-site enzyme, modifies the product specificity of the de novo lipogenic pathway in certain specialized tissues by hydrolyzing the thioester bond linking the growing acyl chain to the 4'-phosphopantetheine of the fatty acid synthase. Modification of one thioesterase II cysteine thiol with thionitrobenzoate inhibited interaction with the S-acyl-fatty acid synthase substrate but not with acyl-CoA model substrates. The identity of the sensitive cysteine residue was determined by treatment of the thionitrobenzoyl enzyme with cyanide and cleavage at the amino-terminal side of the S-cyanocysteinyl residue. Two small cleavage products were isolated; their molecular masses (889 and 675 Da) and amino acid compositions indicated that both originated from cleavage at Cys256. A new technique of electrospray ionization mass spectrometry was utilized to confirm that the heterogeneity displayed by the products of S-cyanocysteinyl cleavage resulted from the presence, in the purified preparations, of both full length and a truncated form of the enzyme missing the carboxyl-terminal Leu-Thr peptide. The proportion of full-length polypeptide present appeared to correlate with the activity of the enzyme toward its natural substrate. The results of modification of Cys256 by thionitrobenzoate and removal of residues 262 and 263 by endogenous proteases indicate that integrity of the carboxyl-terminal region is important for interaction with its acyl-fatty acid synthase substrate. PMID- 2318833 TI - Human beta-fibrinogen gene expression. Upstream sequences involved in its tissue specific expression and its dexamethasone and interleukin 6 stimulation. AB - The synthesis of fibrinogen in the liver is drastically enhanced during the inflammatory process. Two factors are involved: glucocorticoids and the hepatocyte stimulating factor which is identical with interleukin 6 (Il6), also called interferon beta 2. The function of the 5'-flanking region of the human beta-fibrinogen (beta-Fg) gene has been studied by deletion analysis with the chloramphenicol acetyltransferase (CAT) gene as a transient expression vector. In this analysis, a fragment containing 150 base pairs (bp) upstream from the cap site is sufficient to drive expression of the CAT gene in the hepatoma cells HepG2, but not in HeLa cells. The beta-Fg gene is induced by dexamethasone and Il6 in HepG2. We identify a domain located between -2900 and -1500 bp upstream from the transcription start point involved in dexamethasone sensibility. This distal regulatory region can confer hormone inductibility to a heterologous promoter and exert its effect in either orientation. The sequence located between -150 and -82 bp upstream from the transcription start point is responsive for the Il6-stimulated expression. This 68-bp sequence contains probably all the cis acting Il6-responsive element of the human beta-Fg gene. PMID- 2318834 TI - Transcription termination factor rho has three distinct structural domains. AB - The domain structure of transcription termination factor rho was analyzed by partial trypsin cleavage and by photoaffinity labeling with ATP and oligo(C)5. A rho subunit consists of three distinct domains of nearly equal size that are connected by trypsin-sensitive linker segments. The amino-terminal domain binds to oligo(C)5 and has sequence segments with extended similarity to conserved elements in other RNA-binding proteins and a segment that has identities with another known cytidine nucleotide-binding protein. The middle domain has the ATP binding site and has most of the sequence segments with similarity to conserved elements in other nucleoside triphosphate-binding proteins. The function of the third domain, the carboxyl-terminal domain, has not been identified. Both the amino- and carboxyl-terminal domains are relatively resistant to further trypsin treatment. The ATP-binding domain is also relatively resistant when it is linked to the amino-terminal, RNA-binding domain, but has not been detected as a separate digestion product. This result plus the finding that ADP and ATP inhibit the cleavage in the linker between the two domains indicate that those domains interact intimately in spite of their functional distinctions. PMID- 2318835 TI - Free fatty acids associated with the high molecular weight aminoacyl-tRNA synthetase complex influence its structure and function. AB - Aminoacyl-tRNA synthetases from higher eukaryotes often are isolated as high molecular weight complexes associated with other components such as lipids. Since hydrophobic interactions are involved in the organization of the complex, it has been suggested that interaction of synthetases with these lipids might be important for their structure and function. Delipidation is known to affect certain properties of synthetases within the complex including sensitivity to detergents plus salts, temperature inactivation, hydrophobicity, sensitivity to proteases, and, as shown here, sensitivity to p-mercuribenzoate and sites of papain cleavage. Of the lipids known to co-purify with the complex, cholesterol esters, phospholipids and free fatty acids, we show that the particular lipids responsible for many of these changes are the free fatty acids. Specific removal of fatty acids results in a complex with properties similar to one totally delipidated by detergent treatment, and readdition of the fatty acid fraction reverses the effects. The fatty acid fraction contains both saturated and unsaturated fatty acids, but unsaturated fatty acids are much more effective in reversing the properties of the delipidated complex that are saturated fatty acids. These results indicate that the free fatty acids co-purifying with the synthetase complex bind to the synthetases and affect their structure and function. PMID- 2318836 TI - Purification of a novel type of calcium-activated neutral protease from rat brain. Possible involvement in production of the neuropeptide kyotorphin from calpastatin fragments. AB - We have found a novel type of Ca2(+)-activated neutral protease in rat brain cytosol which cleaves -Tyr-Arg-containing calpastatin fragments to release the neuropeptide kyotorphin. This enzyme was purified about 26,000-fold by column chromatography as follows: DE52 cellulose, Ultrogel AcA 44, thiopropyl-Sepharose 6B, second DE52 cellulose, Ultrogel AcA 34, and blue Sepharose CL-6B. The molecular mass of the enzyme was estimated to be 65-75 kDa by gel filtration. The purified enzyme gave a single band of 74 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Some properties of this enzyme were similar to those of the calpains, i.e. an absolute requirement for Ca2+, maximal activity at neutral pH, and inhibition by sulfhydryl reagents such as p chloromercuriphenylsulfonic acid and N-ethylmaleimide. However, it differs from the calpains in that it possesses no caseinolytic activity, separates from the calpains on the first DE52 column, and is insensitive to leupeptin and E-64 (N-[N (L-3-trans-carboxyoxrian-2-carbonyl)-L-leucyl]agmatine). Thus, the molecular mass, the substrate specificity, the chromatographic behavior, and the inhibitor spectrum all suggest that this enzyme is a novel type of Ca2(+)-activated neutral protease. PMID- 2318837 TI - The flavin-containing monooxygenase enzymes expressed in rabbit liver and lung are products of related but distinctly different genes. AB - Preparations of mRNA isolated from rabbit lung and liver were used in the construction of libraries that were screened for cDNAs encoding the pulmonary or hepatic isozyme of the flavin-containing monooxygenase. The hepatic library was screened with cDNA encoding the flavin-containing monooxygenase expressed in pig liver, and a clone containing a 2.0-kilobase insert was detected and isolated. This cDNA insert encoded a protein of 535 amino acids with a primary structure 87% identical to that of the pig flavin-containing monooxygenase. The pulmonary library was screened with polyclonal antibodies to the flavin-containing monooxygenase expressed in rabbit lung, and a clone containing a 2.6-kilobase insert was detected and isolated. Although the protein encoded by this insert also contained 535 amino acids, its primary sequence was only 56% identical to that of the liver enzyme. The sequences of several peptides obtained by digestion of the purified rabbit pulmonary flavin-containing monooxygenase with trypsin matched exactly with sequences derived from the cDNA structure. Tissue-specific distribution of mRNA for the hepatic and pulmonary isozymes of the flavin containing monooxygenase was consistent with the distribution of protein, an indication that expression of flavin-containing monooxygenase is controlled at the level of transcription. Analysis of genomic DNA indicates that both the hepatic and pulmonary enzymes may be products of single genes. PMID- 2318838 TI - Purification and functional characterization of adenovirus ts111A DNA-binding protein. Fluorescence studies of protein-nucleic acid binding. AB - The adenovirus single-stranded DNA (ssDNA)-binding protein (DBP) is necessary for the elongation step in viral DNA replication. In an attempt to characterize the putative ssDNA-binding domain of the DBP, we purified and characterized the Ad2ts111A DBP, which contains a glycine-to-valine substitution at amino acid 280. This mutation is adjacent to that in the previously studied Ad2+ND1ts23. Ad2+ND1ts23 exhibits a temperature-sensitive defect in DNA replication, and its DBP has previously been shown to bind ssDNA with reduced affinity. Ad2ts111A DBP, like Ad2+ND1ts23, does not support adenovirus DNA replication in vitro at elevated temperatures. However, the Ad2ts111A DBP binds ssDNA more tightly than does Ad2+ND1ts23 and is not temperature sensitive in this function. To determine the nucleic acid-binding properties of DBP, we applied spectrofluorometric techniques, which had not been used previously to study adenovirus DBP. Using the homopolynucleotide poly(1,N6)-ethenoadenylic acid (poly(r epsilon A], we have determined that the binding site size is approximately 16 nucleotides. In 20 mM NaCl, the Ad2wt, Ad2ts111A, and Ad2+ND1ts23 DBP proteins all bound stoichiometrically to poly(r epsilon A) with overall apparent affinities above 108 M-1. Based on titrations carried out at higher salt concentrations, however, the stability of these complexes did appear to increase in the order Ad2+ND1ts23 less than Ad2ts111A less than Ad2wt. By these techniques, we have confirmed also that the DBP of another temperature-sensitive mutant, H5ts107, like the Ad2ts111A DBP, retains its ability to bind ssDNA even at a restrictive temperature utilizing the salt concentration compatible with adenovirus DNA replication in vitro. The H5ts107 DBP, which contains an amino acid substitution at position 413, is defective for in vitro replication at nonpermissive temperature but is not temperature sensitive for binding to ssDNA. In summary, our results indicate that the replication defects of the Ad2ts111A are similar to those of H5ts107 and cannot be attributed to defective, nonspecific ssDNA binding by the DBP. It appears that ssDNA binding by itself is not sufficient to account for the role of DBP in adenovirus DNA replication. PMID- 2318839 TI - Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation. AB - The effects of basic fibroblast growth factor (bFGF) on terminal differentiation of chondrocytes and cartilage-matrix calcification were investigated. Rabbit growth-plate chondrocytes maintained as a pelleted mass in a centrifuge tube produced an abundant proteoglycan matrix during the matrix-maturation stage, yielding a cartilage-like tissue. Thereafter, they terminally differentiated to hypertrophic chondrocytes which produced high levels of alkaline phosphatase. These cells induced extensive calcification of the matrix in the absence of additional phosphate (Kato, Y., Iwamoto, M., Koike, T., Suzuki, F., and Takano, Y. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 9552-9556). Addition of bFGF to the chondrocyte cultures abolished the increases in alkaline phosphatase activity, 45Ca deposition, and the calcium content. These effects were dose-dependent, reversible, and observed in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. The inhibitory effects could be observed only when chondrocytes were exposed to bFGF in a transition period between the matrix-maturation and hypertrophic stages. As chondrocytes differentiated to hypertrophic cells, bFGF became less effective in inhibiting the expression of the mineralization-related phenotypes. The present study also shows that although the rate of [35S]sulfate incorporation into large, chondroitin sulfate proteoglycan in the cell-matrix fraction is very high during the matrix-maturation stage, it abruptly decreases by 90% after terminal differentiation. Furthermore, the terminal differentiation associated decrease in proteoglycan synthesis was delayed by bFGF. These results provide evidence that bFGF inhibits terminal differentiation of chondrocytes and calcification. PMID- 2318840 TI - Expression of the bile acid transport protein during liver development and in hepatoma cells. AB - The expression of the hepatocyte Na(+)-dependent bile acid transport protein during liver development and in hepatoma cells has been characterized using a monoclonal antibody (mAb 25D-1) which specifically recognizes this 49-kDa carrier system. mAb binding studies demonstrated a greatly reduced concentration of this transport protein on the surface of hepatoma tissue culture (HTC) cells, a result consistent with the greater than 95% reduction in bile acid transport capacity when compared with normal adult hepatocytes. Immunoprecipitation procedures with 25D-1 were utilized to quantitate the presence of this transport protein in HTC cells as well as in adult hepatocytes that had been labeled with [35S]methionine or Na125I. These studies indicate that the 49-kDa transport protein is not expressed either on the surface or in any intracellular compartment in HTC cells. mAb binding to fetal cells (day 17) also indicated a greatly decreased number of transport molecules in the plasma membrane. Total cell content of this carrier protein during the next 7 weeks of liver development, as measured by immunoprecipitation, increased in a linear fashion reaching 92% of the adult level at 4 weeks after birth, which parallels the increase in transport function. These results demonstrate that bile acid transport capacity is directly related to the level of expression of this 49-kDa membrane protein. PMID- 2318841 TI - Variants of the carboxyl-terminal KDEL sequence direct intracellular retention. AB - Soluble proteins which reside in the lumen of the endoplasmic reticulum share a common carboxyl-terminal tetrapeptide Lys-Asp-Glu-Leu (KDEL). Addition of the tetrapeptide to a normally secreted protein is both necessary and sufficient to cause retention in the endoplasmic reticulum. In order to characterize the critical residues in the KDEL signal, cDNAs encoding proneuropeptide Y (pro-NPY) with the 4-amino acid carboxyl-terminal extension KDEL or a series of KDEL variants were expressed in the AtT-20 cell line. AtT-20 cells, a mouse anterior pituitary corticotrope cell line, synthesize, process, and secrete the pro ACTH/endorphin precursor. Since post-translational processing in AtT-20 cells has been extensively characterized, it provides a model system in which the processing of a foreign peptide precursor (pro-NPY) and the endogenous precursor (pro-ACTH/endorphin) can be compared. Altered cDNAs encoding pro-NPY with KDEL, DKEL, RDEL, KNEL, KDQL, or KDEA at the COOH terminus were used to generate stable AtT-20 cell lines. The processing of pro-NPY to neuropeptide Y and the carboxyl terminal peptide was studied using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, tryptic peptide mapping, and radiosequencing. Addition of the tetrapeptides KDEL, DKEL, RDEL, or KNEL to the COOH terminus of the neuropeptide Y precursor, a peptide hormone normally processed and secreted from neuronal cells, caused complete intracellular retention of the unprocessed prohormone in AtT-20 cells. However, KDQL and KDEA-extended pro-NPY molecules were processed and secreted like wild-type pro-NPY when expressed in AtT-20 cells. The secretion of proNPY-derived peptides in these cell lines paralleled secretion of endogenous pro-ACTH/endorphin-derived products under both basal and stimulated conditions. These mutagenesis studies demonstrate that variants of the KDEL retention signal can direct intracellular retention. PMID- 2318842 TI - The detection of kinetic intermediate(s) during refolding of rhodanese. AB - Recent studies showed that the enzyme rhodanese could be reversibly unfolded in guanidinium chloride (GdmCl) if aggregation and oxidation were minimized. Further, these equilibrium studies suggested the presence of intermediate(s) during refolding (Tandon, S., and Horowitz, P. (1989) J. Biol. Chem. 264, 9859 9866). The present work shows that native and refolded enzymes are very similar in structural and functional characteristics. Kinetics of denaturation/renaturation were used to detect the folding intermediate(s). The shift in fluorescence wavelength maximum was used to monitor the structural changes during the process. First order plots of the structural changes during unfolding and refolding show nonlinear curves. The refolding occurs in at least two phases. The first phase is very fast (t1/2 much less than 30 s) and accounts for the partial regain in the structure but not in the activity. The second phase is slow (t1/2 = 2.9 h) during which the enzyme fully regains its structure along with the activity. The fractional renaturation of rhodanese due to the fast phase, monitored in various concentrations of GdmCl, describes a transition centered at 3.5 M GdmCl which is very similar to the higher of the two transitions observed in the reversible refolding. All of these findings support the presence of detectable intermediate(s) during folding of rhodanese. PMID- 2318843 TI - Synthetic fragments of calmodulin calcium-binding site III. A test of the acid pair hypothesis. AB - The acid pair hypothesis describing the interaction of calcium with the helix loop-helix conformation of EF hands in calmodulin and related proteins predicts that these calcium-binding sites will have increased affinity for calcium if the anionic amino acid dentates in the loop region which interact directly with the cation are paired on the axial vertices of the resulting octahedral arrangement of chelating residues about the cation. As a test of this hypothesis, synthetic 33 residue analogs of bovine brain calmodulin calcium-binding site III have been prepared by the solid-phase method and analyzed for calcium affinity. The native sequence has a Kd of 735 microM for calcium and contains three anionic ligands which assume the +x, +y, and -z coordinates of the octahedral arrangement about the cation, thus precluding any pairing of the anionic ligands. This dissociation constant is 26 times weaker than that obtained from a synthetic analog of the sequentially homologous calcium-binding site III of rabbit skeletal TnC (Kd = 28 microM) which has four anionic ligands paired on the x and z axes. An analog of calmodulin site III with substitutions in the chelating residues at positions 1, 3, 5, 7, 9, and 12 of the 12-residue loop region to make these positions identical to those of rabbit skeletal troponin C site III decreased the calcium dissociation constant of the calmodulin peptide to 19 microM, similar to the troponin C peptide. Two synthetic analogs of calmodulin site III which contain three anionic ligands with two ligands paired on the x axis and two on the z axis have a Kd for calcium of 524 and 59 microM, respectively. This study provides strong support for and a better definition of the acid pair hypothesis and further demonstrates the usefulness of synthetic calcium-binding fragments in delineating the mechanism of calcium regulation of calmodulin and related proteins. PMID- 2318844 TI - Mechanistic investigation of doxycycline photosensitization by picosecond-pulsed and continuous wave laser irradiation of cells in culture. AB - In order to elucidate the photophysical mechanisms of cellular phototoxicity sensitized by doxycycline, MGH-U1 human bladder carcinoma cells in vitro were treated with 20.7 microM doxycycline and irradiated with either a pulsed (lambda = 355 nm, pulse duration = 24 ps) or a continuous wave (lambda = 351 nm) laser. Cumulative radiant exposure and irradiance were systematically varied in experiments with both lasers. Phototoxicity was assessed by epifluorescence microscopy of unfixed cells using rhodamine 123 labeling of mitochondria. With the continuous wave source, the cumulative radiant exposure required for induction of phototoxic injury was independent of irradiance. With the 24-ps pulsed source, a significantly lower cumulative radiant exposure was required to induce the phototoxicity when the peak irradiance was 5.8 x 10(7) or 1.3 x 10(8) watts cm-2 compared with when peak irradiance was either lower (6.0 x 10(6) watts cm-2) or higher (7.6 x 10(8) watts cm-2). The measured fluorescence lifetimes of doxycycline in buffered saline solution were longer than the laser pulse duration of 24 ps. The increased efficiency of photosensitization at the optimal peak irradiance in the ps domain appears to result from sequential multiphoton absorption involving higher excited states of the singlet manifold. At the highest irradiance studied, on the other hand, reduced efficiency of photosensitization is attributed to increased photodegradation of doxycycline from higher excited states by processes such as photoionization. A model consistent with these observations is presented along with calculations, based on simple rate equations, that fit the essentials of the proposed model. PMID- 2318845 TI - Cholesterol is required for the reconstruction of the sodium- and chloride coupled, gamma-aminobutyric acid transporter from rat brain. AB - The reconstruction of the purified sodium- and chloride-coupled gamma aminobutyric acid transporter from rat brain into asolectin liposomes requires the addition of brain lipids (Radian, R., and Kanner, B. I. (1985) J. Biol. Chem. 260, 11859-11865). The reconstitution assay was used to identify the component(s) from brain lipids responsible for the stimulation during the fractionation of brain lipids. The distribution of the active component was found to be similar to that of cholesterol. Furthermore, cholesterol was found to mimic the effect of brain lipids and it stimulated the transport activity up to 20-fold. Optimal reconstituted transport activity was achieved with mixtures of cholesterol and any one of several phospholipids, such as phosphatidylcholine, phosphatidylserine or phosphatidylglycerol. gamma-Aminobutyric acid transport in these liposomes of defined composition exhibited all the properties of the native transporter, such as the absolute dependence on sodium and chloride and electrogenicity. Cholesterol could not be replaced by cholest-4-en-3one and other steroids, and thus its effect is probably not due to effects on membrane fluidity. The requirement was also not due to effects on intactness of the liposomes or incorporation of proteins into them. Furthermore it was found that the reconstitution of the sodium and potassium coupled L-glutamic acid transporter from rat brain also required cholesterol. However, in this case the optimal activity was reached by 4-5-fold lower levels of cholesterol than those necessary for gamma-aminobutyric acid transport. When cholesterol depletion from the transporters was incomplete, addition of exogenous brain lipids was not required. Thus, if the cholesterol was still associated with the transporter proteins, its final concentration, as a fraction of the total lipids present in the reconstitution mixture, was only about 0.01 mol%. Thus, it is likely that the effects of cholesterol are due to direct interactions with the cotransporters and not to an average effect on membrane properties. PMID- 2318846 TI - Kinetic determination of the effects of ADP-ribosylation on the interaction of eukaryotic elongation factor 2 with ribosomes. AB - The effect of ADP-ribosylation on the function of eukaryotic elongation factor 2 (EF-2) was investigated by kinetic analysis of the EF-2-catalyzed hydrolysis of GTP in the presence of ribosomes and by direct determination of the affinity of the modified factor for the ribosome. Under conditions where the concentration of EF-2 was rate-limiting, the ADP-ribosylation reduced the maximum rate of GTP hydrolysis and the second order rate constant Kcat/Km by approximately 50%. A similar decrease in Kcat and Kcat/Km was observed when the concentration of ribosomes were kept rate-limiting. The affinity of EF-2 for the pretranslocation type of ribosomes was reduced by 2 orders of magnitude after ADP-ribosylation. No effect was observed in the interaction with the post-translocation type of ribosomes, the ribosomal conformation responsible for activation of the EF-2 dependent GTPase. We conclude that the ADP-ribosylation affects both the association of the modified factor with pretranslocation ribosomes and the hydrolytic capacity of the factor. PMID- 2318847 TI - Interaction of heparin cofactor II with neutrophil elastase and cathepsin G. AB - We investigated the interaction of the human plasma proteinase inhibitor heparin cofactor II (HC) with human neutrophil elastase and cathepsin G in order to examine 1) proteinase inhibition by HC, 2) inactivation of HC, and 3) the effect of glycosaminoglycans on inhibition and inactivation. We found that HC inhibited cathepsin G, but not elastase, with a rate constant of 6.0 x 10(6) M-1 min-1. Inhibition was stable, with a dissociation rate constant of 1.0 x 10(-3) min-1. Heparin and dermatan sulfate diminished inhibition slightly. Both neutrophil elastase and cathepsin G at catalytic concentrations destroyed the thrombin inhibition activity of HC. Inactivation was accompanied by a dramatic increase in heat stability, as occurs with other serine proteinase inhibitors. Proteolysis of HC (Mr 66,000) produced a species (Mr 58,000) that retained thrombin inhibition activity, and an inactive species of Mr 48,000. Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC. Since cathepsin G is inhibited by HC and also inactivates HC, we conclude that cathepsin G participates in both reactions simultaneously so that small amounts of cathepsin G can inactivate a molar excess of HC. High concentrations of heparin and dermatan sulfate accelerated inactivation of HC by neutrophil proteinases, with heparin having a greater effect. Heparin and dermatan sulfate appeared to alter the pattern, and not just the rate, of proteolysis of HC. We conclude that while HC is an effective inhibitor of cathepsin G, it can be proteolyzed by neutrophil proteinases to generate first an active inhibitor and then an inactive molecule. This two-step mechanism might be important in the generation of chemotactic activity from the amino-terminal region of HC. PMID- 2318848 TI - Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system. AB - The organization and structure of the gene coding for plasminogen has been determined by a combination of in vitro amplification of leukocyte DNA from normal individuals and isolation of unique clones from three different human genomic libraries. These clones were characterized by restriction mapping, Southern blotting, and DNA sequencing. The gene for human plasminogen spanned about 52.5 kilobases of DNA and consisted of 19 exons separated by 18 introns. DNA sequence analysis revealed that the five kringle structures in plasminogen were coded by two exons. The nucleotides in the introns at the intron-exon boundaries were GT-AG analogous to those found in other eukaryotic genes. Three polyadenylation sites for plasminogen mRNA were also identified. When the amino acid sequences deduced from the genomic DNA and cDNAs of plasminogen were compared with that of the plasma protein determined by amino acid sequence analysis, an apparent amino acid polymorphism was observed in several positions of the polypeptide chain. Nucleotide sequence analysis of the amplified genomic DNAs and genomic clones also revealed that the plasminogen gene was very closely related to several other proteins, including apolipoprotein(a). This protein may have evolved via duplication and exon shuffling of the plasminogen gene. The presence of another plasminogen-related gene(s) in the human genomic library was also observed. PMID- 2318849 TI - Synthesis and antiretroviral activity of phospholipid analogs of azidothymidine and other antiviral nucleosides. AB - Treatment of acquired immunodeficiency syndrome with azidothymidine (AZT, zidovudine) reduces p24 antigenemia, increases CD4 lymphocyte counts, reduces the frequency and severity of opportunistic infections and prolongs life. However, AZT and other dideoxynucleosides do not diminish the ability to isolate human immunodeficiency virus (HIV) from peripheral blood mononuclear cells. Failure to clear infectious virus may be due to inadequate inhibition of virus production by macrophages, a major reservoir of HIV infection. Cells of the macrophage lineage take up large amounts of parenterally administered liposomal material. To direct larger proportions of antiretroviral nucleosides to this important HIV reservoir, we synthesized phosphatidylAZT, AZT diphosphate dipalmitin, phosphatidylddC and phosphatidylddT, novel phospholipid prodrugs which are readily incorporated into phospholipid bilayers. These liposomal liponucleotides were shown to have antiretroviral activity in HIV-infected U937 and CEM cells. In vivo, it is anticipated that liposomes containing the antiretroviral liponucleotides will be taken up in large proportion by macrophages. This property would appear to make phosphatidylAZT and the related compounds promising candidate agents with a special potential to target drug to the macrophage reservoir of HIV infection, thereby reducing the toxicity of the antiviral nucleosides to other cells. PMID- 2318850 TI - Odorant-binding protein. Characterization of ligand binding. AB - We have characterized the odorant binding properties of purified bovine odorant binding protein (OBP) using as a ligand [3H]3,7-dimethyloctan-1-ol ([3H]DMO). A broad variety of odorants, including terpenes, aldehydes, esters, and musks, bind to OBP with affinities of 0.2 to 100 microM. Odorant affinities for OBP correlate most closely with their stimulation of an odorant-sensitive adenylyl cyclase as well as hydrophobicity. We also measured the kinetics of binding for the ligands, [3H]DMO and 2-isobutyl-3-[3H]methoxypyrazine. Dissociation of both is markedly accelerated in the presence of excess unlabeled ligand. Competition curves of displacers for [3H]DMO binding are shallow, and saturation binding isotherms for 3H-odorants are curvilinear. These kinetic and equilibrium binding properties suggest that OBP interactions with odorant ligands are negatively cooperative. PMID- 2318851 TI - Cysteine conjugate S-oxidase. Characterization of a novel enzymatic activity in rat hepatic and renal microsomes. AB - Cysteine conjugate S-oxidase activity, with S-benzyl-L-cysteine as substrate, was found mostly in the microsomal fractions of rat liver and kidney. In the presence of oxygen and NADPH, S-benzyl-L-cysteine is converted to S-benzyl-L-cysteine sulfoxide; no S-benzyl-L-cysteine sulfone was detected. The Vmax for S-benzyl-L cysteine sulfoxide formation by kidney microsomes was nearly 3-fold greater than the rate measured with liver microsomes. Inclusion of catalase, superoxide dismutase, glutathione, butylated hydroxyanisole, the peroxidase inhibitor, potassium cyanide, the cytochrome P-450 inhibitors, 1-benzylimidazole and metyrapone, or a monoclonal antibody to cytochrome P-450 reductase did not inhibit the metabolic reaction. Flavin-containing monooxygenase alternate substrates, N,N-dimethylaniline, n-octylamine, and methimazole inhibited the S oxidase activities. Analogues of S-benzyl-L-cysteine, S-methyl-L-cysteine, and S (1,2-dichlorovinyl)-L-cysteine inhibited the S-benzyl-L-cysteine S-oxidase activities, whereas S-carboxymethyl-L-cysteine and S-benzyl-L-cysteine methyl ester had no effect. These results provide clear evidence against the involvement of reactive oxygen intermediates or cytochrome P-450 in the sulfoxidation of S benzyl-L-cysteine and indicate that the S-oxidase activities may be associated with flavin-containing monooxygenases which exhibit selectivity in the interaction with cysteine S-conjugates. PMID- 2318852 TI - Affinity labeling of rat liver and kidney type I 5'-deiodinase. Identification of the 27-kDa substrate binding subunit. AB - Extrathyroidal production of 3,3',5-triiodothyronine from the thyroid secretory product, thyroxine, is catalyzed by tissue-specific iodothyronine 5'-deiodinases. Type I 5'-deiodinase (5'D-I) produces greater than 75% of the T3 found in the circulation and in thyroid hormone-responsive tissues and is most abundant in rat liver and kidney. In this study, we used the bromoacetyl derivatives of T4 (N bromoacetyl-[125I]L-thyroxine, BrAcT4) and T3 (N-bromoacetyl-[125I]3,3',5 triiodothyronine, BrAcT3) as alkylating affinity labels to identify 5'D-I-related protein(s). BrAcT4 and BrAcT3 rapidly and irreversibly inactivated 5'D-I activity in liver and kidney microsomes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of affinity labeled 5'D-I preparations showed that approximately 80% of the affinity label was incorporated into a protein with a Mr of 27,000 (p27). 5'D-I substrates and inhibitors specifically blocked affinity labeling of p27 with a rank order of potency (BrAcT4 greater than BrAcT3 greater than 3,5,3' triiodothyronine (rT3) approximately flavone EMD 21388 greater than iodoacetate greater than N-acetyl-T4 (NAcT4) greater than N-acetyl-T3 (NAcT3] identical to that determined for inhibition of 5'-deiodination. Hyper- and hypothyroidism induced increases and decreases in 5'D-I activity, respectively, were matched by comparable changes in the quantity of affinity labeled p27. BrAcT3 was a less effective affinity label for p27 and minor labeling of a new band with 53 kDa was observed. Molecular sieve chromatography of detergent-solubilized 5'D-I showed coincident peaks of p27 and 5'-deiodinating activity with an apparent Mr approximately 51,000. Two-dimensional gel electrophoresis showed that p27 was a single polypeptide with a pI of 6.1. Approximately 2-5 pmol of p27 were present per mg of liver microsomal protein, equal to previous estimates for 5'D-I content. Our results suggest that p27 represents the substrate binding subunit of type I 5'-deiodinase, the enzyme catalyzing the key reaction in the activation of T4 to the thyromimetically active T3. PMID- 2318853 TI - Involvement of protein kinase C in prostaglandin E2-induced catecholamine release from cultured bovine adrenal chromaffin cells. AB - We recently reported that prostaglandin (PG) E2 stimulated phosphoinositide metabolism in cultured bovine adrenal chromaffin cells and that PGE2 and ouabain induced a gradual secretion of catecholamines from the cells (Yokohama, H., Tanaka, T., Ito, S., Negishi, M., Hayashi, H., and Hayaishi, O. (1988) J. Biol. Chem. 263, 1119-1122). Here we examined the involvement of two signal pathways, Ca2+ mobilization and protein kinase C activation resulting from phosphoinositide metabolism, in the PGE2-induced catecholamine release. Either the Ca2+ ionophore ionomycin or 12-O-tetradecanoylphorbol 13-acetate (TPA) could enhance the release in the presence of ouabain, and ionomycin-induced release was additive to PGE2 induced release, but TPA-induced release was not additive. PGE2 dose-dependently stimulated the formation of diacylglycerol and caused the translocation of 4% of the total protein kinase C activity to become membrane-bound within 5 min. These effects were specific for PGE2 and PGE1 among PGs tested (PGE2 = PGE1 greater than PGF2 alpha greater than PGD2). Furthermore, the phosphoinositide-specific phospholipase C inhibitor neomycin inhibited PGE2-induced accumulation of inositol phosphates, diacylglycerol formation, translocation of protein kinase C, and also stimulation of catecholamine release. Both PGE2- and TPA-induced release were inhibited by the depletion of protein kinase C caused by prolonged exposure to TPA, but ionomycin-induced release was not inhibited. We recently found that the amiloride-sensitive Na+, H+-antiport participates in PGE2-evoked catecholamine release (Tanaka, T., Yokohama, H., Negishi, M., Hayashi, H., Ito, S., and Hayaishi, O. (1990) J. Neurochem. 54, 86-95). In agreement with our recent report, PGE2 and TPA induced a sustained increase in intracellular pH that was abolished by the protein kinase C inhibitor staurosporine but not by the calmodulin inhibitor W-7. Ionomycin also induced a marked increase in intracellular pH, but this increase was abolished by W-7 but not by staurosporine. These results demonstrate that PGE2-induced activation of the Na+, H(+)-antiport and catecholamine release in the presence of ouabain are mediated by activation of protein kinase C, rather than by Ca2+ mobilization, resulting from phosphoinositide metabolism. PMID- 2318854 TI - A point mutation at the putative ATP-binding site of protein kinase C alpha abolishes the kinase activity and renders it down-regulation-insensitive. A molecular link between autophosphorylation and down-regulation. AB - A protein kinase C alpha (PKC alpha) cDNA confers increased phorbol ester binding activity to intact cells when transiently expressed in COS cells or expressed stably in transfected rat 3Y1 fibroblasts. A point mutant (PKC alpha K----R) of PKC alpha, where Lys368 at the putative ATP-binding site is replaced with Arg, confers enhanced phorbol ester binding activity to both transiently and stably expressed COS and 3Y1 cells, respectively. Like endogenous and exogenously expressed wild type PKC alpha, the mutant PKC alpha K----R is translocated from the cytosol to the particulate fraction when cells are treated with a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). On the other hand, the mutant PKC alpha K----R is not degraded when cells are treated with TPA, making a clear contrast to wild type PKC alpha; i.e. the mutant is resistant to TPA-mediated down-regulation. The mutant lacks kinase activity as expected, as judged by autophosphorylation and by a kinase assay using a peptide substrate, although the phorbol ester binding activity remains intact. These results suggest a link between the kinase activity of PKC alpha and the sensitivity to TPA-mediated proteolytic degradation. We propose that autophosphorylation of PKC alpha is a prerequisite for proteolytic cleavage associated with the down-regulation of PKC alpha. PMID- 2318855 TI - In vivo and in vitro noncovalent association of excised alpha 1 (I) amino terminal propeptides with mutant pN alpha 2(I) collagen chains in native mutant collagen in a case of Ehlers-Danlos syndrome, type VII. AB - The cause of the Ehlers-Danlos syndrome Type VII (EDS VII) is considered to be defective removal of the amino-terminal propeptide (N-propeptide) of Type I procollagen due to deficiency of procollagen N-proteinase, the enzyme responsible for the normal proteolytic excision of this precursor-specific domain. Molecules retaining the N-propeptide (pN-collagen molecules) are thought to cause defective fibrillogenesis and cross-linking which eventuate in dramatic joint laxity and joint dislocations, the clinical hallmark of this variety of EDS. Recent studies demonstrate that some EDS VII patients harbor small deletions of either the pro alpha 1(I) or pro-alpha 2(I) chain of Type I procollagen. We have found an 18 amino acid deletion (due to exon outsplicing) in a mutant pro-alpha 2(I) chain from such a patient. The deleted peptide is the junctional segment (N telopeptide) linking the alpha 2(I) N-propeptide and major triple helical domains; loss of this short segment results in union of these latter domains and produces a shortened pN alpha 2(I) chain. Directly extracted tissue collagen and pepsin-digested fibroblast collagen contain this mutant pN alpha 2(I) chain and normal alpha 1(I) chains, but not pN alpha 1(I) chains, indicating that the relatively larger alpha 1(I) N-propeptide is excised from the related alpha 1(I) chains. The fate of this alpha 1(I) N-propeptide was unclear and therefore whether or not the intact N-propeptide was, in fact, retained in native mutant collagen was also unclear. In this paper, we describe morphologic, chemical, and immunochemical studies which indicate that the alpha 1(I) N-propeptide is retained in noncovalent association with the mutant pN alpha 2(I) chain in native mutant collagen molecules both in vivo and in vitro. In both instances, the alpha 1(I) N-propeptides are proteolytically cleaved from the related alpha 1(I) chains. These data suggest that retention of a partially cleaved, but essentially intact N-propeptide in mutant collagen may play a role in the pathogenesis of this disease. PMID- 2318856 TI - Selective inhibition of integrin function by antibodies specific for ligand occupied receptor conformers. AB - We have hypothesized that ligand-induced binding sites (LIBS), i.e. sites expressed on cell surface receptors only after ligand binding causes the receptor to change shape, mediate subsequent biological events. To test this hypothesis, we have raised monoclonal antibodies that preferentially react with an integrin (platelet glycoprotein (GP) IIb-IIIa) after it bind Arg-Gly-Asp-containing ligands. The 13 anti-LIBS antibodies obtained define at least three distinct GPIIb-IIIa epitopes; one of these epitopes is also expressed following occupancy of another integrin, the vitronectin receptor. Certain of these LIBSs appear to mediate functions, since the antibodies that define them inhibit GPIIb-IIIa mediated fibrin clot contraction or platelet adhesion to collagen. Nevertheless, none of the anti-LIBS antibodies inhibit binding of the primary ligand, fibrinogen. These data indicate that LIBS may mediate distinct consequences of receptor occupancy. PMID- 2318857 TI - Fungal elicitor triggers rapid, transient, and specific protein phosphorylation in parsley cell suspension cultures. AB - Treatment of suspension-cultured parsley (Petroselinum crispum) cells with fungal elicitor triggers rapid, transient and sequential phosphorylation of a number of proteins, as shown by electrophoretic analysis on two-dimensional gels. This response is rapidly reversed by removal of the elicitor from the medium and appears to be specific. It is not observed in cells exposed to other environmental stress factors, such as heat shock, UV irradiation or treatment with mercuric chloride. Pronase digestion of the elicitor has the same negative effect on protein phosphorylation as its previously demonstrated effect on the activation of some pathogen defense-related genes, suggesting a link between these two phenomena. Some of the changes in protein phosphorylation are among the earliest known events following elicitation. The phosphorylation of a neutral 45 kDa protein, which is found in both the microsomal and cytoplasmic fractions, can be observed as early as 1 min after the onset of elicitor treatment. The phosphorylation of a 26-kDa nuclear protein also starts increasing very early. The changes in protein phosphorylation in response to the elicitor are dependent on the presence of Ca2+ in the medium. Our data are compatible with the hypothesis that protein phosphorylation is involved in the signal transduction processes following elicitor recognition by parsley cells. PMID- 2318858 TI - Selective and tandem amplification of a member of the metallothionein gene family in Candida glabrata. AB - Metallothioneins constitute a multigene family in the yeast Candida glabrata. Two genes, designated metallothionein-I (MT-I) and one member of the metallothionein II family (MT-II), were cloned and sequenced previously (Mehra, R. K., Garey, J. R., Butt, T. R., Gray, W. R., and Winge, D. R. (1989) J. Biol. Chem. 264, 19747 19753). Southern analysis of the genomic DNA samples from different wild-type isolates indicated that the MT-I gene was always present as a single copy but multiple (3-9) and tandemly arranged copies of one MT-II gene were present in different strains. Strains of C. glabrata highly resistant to copper salts were obtained by repeated culturing of wild-type isolates in medium containing increasing concentrations of copper sulfate. These strains showed further stable chromosomal amplification (greater than 30 copies) of the MT-II gene. The MT-I gene remained as a single copy. Amplified copies of the MT-II gene were always arranged tandemly. One of the copper-resistant strains acquired more copies of the MT-II gene by apparent duplication of the chromosome carrying this gene. The size of the amplification unit was 1.25 kilobases. The principal MT-I and -II genes of C. glabrata were shown to map to different chromosomes by electrophoretic karyotypic analysis. The length of chromosome carrying MT-II gene increased appreciably in strains exhibiting the highest amplification of this gene. Northern analysis showed increased basal levels of MT-II mRNA in strains having highly amplified MT-II locus. PMID- 2318859 TI - Regulation of fibrinogen assembly. Transfection of Hep G2 cells with B beta cDNA specifically enhances synthesis of the three component chains of fibrinogen. AB - Previous studies indicated that synthesis of B beta chain may be a rate-limiting factor in the production of human fibrinogen since Hep G2 cells contain surplus pools of A alpha and gamma but not of B beta chains, and fibrinogen assembly commences by the addition of preformed A alpha and gamma chains to nascent B beta chains attached to polysomes. To test whether B beta chain synthesis is rate limiting Hep G2 cells were transfected with B beta cDNA, and its effect on fibrinogen synthesis and secretion was measured. Two sets of stable B beta cDNA transfected Hep G2 cells were prepared, and both cell lines synthesized 3-fold more B beta chains than control cells. The B beta-transfected cells also synthesized and secreted increased amounts of fibrinogen. Transfection with B beta cDNA not only increased the synthesis of B beta chain but also increased the rate of synthesis of the other two component chains of fibrinogen and maintained surplus intracellular pools of A alpha and gamma chains. Transfection with B beta cDNA did not affect the synthesis of albumin, transferrin, or anti-chymotrypsin and had a small inhibitory effect on the synthesis of C-reactive protein. Taken together these studies demonstrate that increased B beta chain synthesis specifically causes increased production of the other two component chains of fibrinogen and that unequal and surplus amounts of A alpha and gamma chains are maintained intracellularly. PMID- 2318860 TI - Generation of transforming growth factor-alpha from the cell surface by an O glycosylation-independent multistep process. AB - The precursor for transforming growth factor-alpha (TGF-alpha) is a membrane glycoprotein that can establish contact with epidermal growth factor/TGF-alpha receptors on adjacent cells or can be cleaved to release TGF-alpha that diffuses into the medium. Cleavage of pro-TGF-alpha occurs at Ala/Leu-Ala/Leu-Ala-Val-Val sites located at each end of the mature TGF-alpha sequence. To characterize the cleavage process of pro-TGF-alpha and the role of glycosylation in this process, we have introduced a pro-TGF-alpha expression vector in wild type Chinese hamster ovary (CHO) cells and in the mutant CHO cell clone ldlD that has a reversible defect in protein glycosylation. Analysis of metabolically labeled and cell surface-labeled products immunoprecipitated with antibodies directed against the extracellular TGF-alpha sequence and the cytoplasmic pro-TGF-alpha C-terminal domain shows that cleavage of pro-TGF-alpha in wild type CHO cells occurs in two steps. Both processing steps occur after pro-TGF-alpha reaches the cell surface. In the first step, pro-TGF-alpha rapidly (t1/2 = 30 min) loses the amino-terminal segment that precedes the TGF-alpha sequence. In the second step, pro-TGF-alpha is cleaved at the carboxyl terminus of the TGF-alpha sequence releasing this factor into the medium. This second step is slow (t1/2 = 2 h). The action of pancreatic elastase added to CHO-TGF-alpha cells mimics the first step but not the second one. Synthesis, cell surface exposure, rate of cleavage, and generation of bioactive TGF-alpha in ldlD-TGF-alpha cells are not markedly affected by the lack of N-acetylgalactosamine-dependent protein O-glycosylation or galactose-dependent glycan chain modification. The results indicate that, despite their similarity in amino acid sequence, the two cleavage sites that flank TGF-alpha may be processed with different kinetics which can lead to retention of pro-TGF-alpha on the cell surface. PMID- 2318861 TI - High level bacterial expression of uteroglobin, a dimeric eukaryotic protein with two interchain disulfide bridges, in its natural quaternary structure. AB - Bacterial expression of eukaryotic proteins is a tool of ever-increasing importance in biochemistry and molecular biology. However, the majority of the recombinant eukaryotic proteins that have been expressed in bacteria are produced as fusion proteins and not in their native conformation. In particular, correct formation of quaternary structures by recombinant proteins in bacterial hosts has been reported very rarely. To our knowledge, correct intracellular formation of multimeric structures containing more than one interchain disulfide bridge has not been reported so far. We have constructed three plasmids which are able to direct expression of recombinant rabbit uteroglobin, a homodimeric protein with two interchain disulfide bridges, in Escherichia coli. Among these, the plasmid pLE103-1, in which the expression of recombinant uteroglobin is controlled by a bacteriophage T7 late promoter, is by far the most efficient. With pLE103-1, recombinant uteroglobin production reached about 10% of total bacterial soluble proteins. This protein accumulated in bacterial cells in dimeric form, as it is naturally found in the rabbit uterus. Recombinant uteroglobin was purified to near-homogeneity and its NH2-terminal amino acid sequence was confirmed to be identical to that of its natural counterpart, except for 2 Ala residues the codons for which were added during the plasmid construction. This protein was found to be as active a phospholipase A2 inhibitor as natural uteroglobin on a molar basis. To our knowledge, this is the first report of high level bacterial expression of a full length eukaryotic homodimeric protein with two interchain disulfide bridges in its natural, biologically active form. The plasmid pLE103-1 may be useful to explore structure-function relationships of rabbit uteroglobin. In addition, this plasmid may be useful in obtaining high level bacterial expression of other eukaryotic proteins with quaternary structure, as well as for other general applications requiring efficient bacterial expression of cDNAs. PMID- 2318862 TI - Glucose phosphorylation in tumor cells. Cloning, sequencing, and overexpression in active form of a full-length cDNA encoding a mitochondrial bindable form of hexokinase. AB - In rapidly growing tumor cells exhibiting high glucose catabolic rates, the enzyme hexokinase is markedly elevated and bound in large amounts (50-80% of the total cell activity) to the outer mitochondrial membrane (Arora, K.K., and Pedersen, P.L. (1988) J. Biol. Chem. 263, 17422-17428; Parry, D.M., and Pedersen, P.L. (1983) J. Biol. Chem. 258, 10904-10912). In extending these studies, we have isolated a cDNA clone of hexokinase from a lambda gt11 library of the highly glycolytic, c37 mouse hepatoma cell line. This clone, comprising 4,198 base pairs, contains a single open reading frame of 2,754 nucleotides which encode a 918-amino acid hexokinase with a mass of 102,272 daltons. This enzyme exhibits, respectively, 68 and 32 amino acid differences, including several charge differences, from the recently sequenced human kidney and rat brain enzymes. The putative glucose and ATP binding domains present in the latter two enzymes and in rat liver glucokinase are conserved in the tumor enzyme. At its N-terminal region, tumor hexokinase has a 12-amino acid hydrophobic stretch which is present in the rat brain enzyme but absent in the rat liver glucokinase, a cytoplasmic enzyme. The mature tumor hexokinase protein has been overexpressed in active form in Escherichia coli and purified 9-fold. The overexpressed enzyme binds to rat liver mitochondria in the presence of MgCl2. This is the first report describing the cloning and sequencing of a tumor hexokinase, and the first report documenting the overexpression of any hexokinase type in E. coli. Questions pertinent to the enzyme's mechanism, regulation, binding to mitochondria, and its marked elevation in tumor cells can now be addressed. PMID- 2318864 TI - A novel mechanism of heme-heme interaction in the homodimeric hemoglobin from Scapharca inaequivalvis as manifested upon cleavage of the proximal Fe-N epsilon bond at low pH. AB - The CO-binding kinetics and the optical spectra of the NO derivative of the homodimeric hemoglobin from Scapharca inaequivalvis have been investigated over the range between pH 7.0 and 2.0. In the deoxygenated derivative, protonation of the proximal imidazole at very low pH values and the consequent cleavage of the Fe-N epsilon bond result in a approximately 50-fold enhancement of the rate constant for CO binding, as found in other hemoproteins. However, in the case of the hemoglobin from S. inaequivalvis, the pH profile displays a cooperative behavior (n = 1.8 +/- 0.1), a unique feature that differentiates this protein from any other hemoprotein investigated thus far. Cleavage of the proximal bond in the NO derivative of S. inaequivalvis hemoglobin likewise displays a very steep pH transition. The mode of assembly of the homodimer, in which the heme carrying E and F helices provide the subunit interface and bring the hemes at a much shorter distance (18.4 A) than in vertebrate hemoglobins, is likely to provide the structural basis for this unique behavior. PMID- 2318863 TI - cis-acting negative regulatory element of prolactin gene. AB - The prolactin (PRL) gene in clonal strains of rat pituitary tumor cells in culture (GH cells) exhibit several regulatory responses, similar to the ones observed in rat pituitary gland. A comparative analysis of regulation of PRL gene expression in PRL-producing (PRL+) and PRL-nonproducing (PRL-) GH cells was conducted by monitoring the PRL promoter driven transient expression of chloramphenicol acetyltransferase (CAT) gene in GH4C1 (PRL+) and GH12C1 (PRL-) cells. The PRL promoter activity was drastically inhibited only in PRL nonproducing cells (PRL-) and not in PRL producing cells (PRL+) when a 80-base pair (bp) DNA sequence from 5'-flanking region of PRL gene (located between -330 and -250 bp) was included in the PRL-CAT fusion gene constructs. Furthermore, a DNA/protein interaction involving this 80-bp DNA sequence and a 60-kDa nuclear protein was detected only in PRL- cells but not in PRL+ GH cells. These results suggested that the strain-specific suppression of PRL gene in PRL-, GH12C1 cells was mediated via interaction of a cis-acting negative regulatory element with a negative regulatory trans-acting factor in these cells. The negative regulatory element within the AT-rich 80-bp DNA sequence was mapped immediately adjacent to the site of interaction of trans-activators of PRL gene. PMID- 2318865 TI - Suppression of rat mammary tumor cell growth in vitro by glucocorticoids requires serum proteins. Characterization of wild type and glucocorticoid-resistant epithelial tumor cells. AB - CON8 is a single-cell derived subclone of the 13762NF transplantable, hormone responsive rat mammary tumor that proliferates rapidly in serum-free medium. Addition of either glucocorticoids or calf serum alone caused a slight stimulation of CON8 proliferation. However, glucocorticoids required the presence of specific serum proteins to strongly suppress CON8 cell growth. Furthermore, the anchorage-independent growth of CON8 cells was significantly reduced in the presence of glucocorticoids and serum. We have designated this serum activity GMGSF, for glucocorticoid modulating growth suppression factor. Inhibition of cell growth was limited to steroids with strong glucocorticoid biological activity, while exposure to the glucocorticoid antagonist RU38486 prevented this response. Half-maximal growth inhibition and half-maximal expression of a glucocorticoid-inducible gene product (2 nM) occurred slightly below the half maximal receptor binding of [3H]dexamethasone (10nM). We have also selected a variant mammary epithelial tumor cell line, derived from CON8, denoted 8RUV7, whose proliferation and soft agar colony formation failed to be suppressed by glucocorticoids in the presence of serum. These glucocorticoid-resistant variant cells possess functional glucocorticoid receptors, competently produce the glucocorticoid-responsive gene product plasminogen activator inhibitor, and along with CON8 cells express milk fat globule protein antigens on their cell surface, indicative of their mammary epithelial cell character. We are using this variant line to genetically dissect the molecular mechanism of the glucocorticoid/GMGSF growth suppression pathway in mammary epithelial tumor cells. PMID- 2318866 TI - Inhibition of alpha-crystallin aggregation by gamma-crystallin. AB - The transparency of the mammalian lens is primarily maintained by short range order among the major proteins of the lens fiber cells, the crystallins. Although these proteins are highly conserved at the amino acid sequence level, it has proven difficult to establish that they possess other than structural functions. We find that when non-lens proteins are added to concentrated solutions of alpha crystallin, aggregation is induced, presumably through excluded volume effects. In contrast, the monomeric gamma-crystallins and the low molecular weight form of beta-crystallin (beta L) cause a decrease in the size of alpha-crystallin. When the naturally aggregated form of alpha-crystallin is examined, gamma- and beta L crystallin, as well as a reducing agent, also cause partial dissociation as detected by dynamic light scattering and size exclusion chromatography, while no effect is seen with non-crystallin proteins. Furthermore, the chemical cross linking of alpha-crystallin is inhibited by gamma- and beta L-crystallin but not by other proteins. The ability of gamma-crystallin to inhibit the association of alpha-crystallin is primarily localized to the gamma-II form which contains a high degree of exposed thiols. Only small amounts of gamma- and beta L crystallin, however, can be cross-linked to alpha-crystallin in mixtures of the three proteins even at very high protein concentrations. These results suggest that one possible role for the lower molecular weight crystallins may be to minimize through a reductive effect the intrinsic tendency of alpha-crystallin to aggregate, an association reaction implicated in the loss of lens transparency. PMID- 2318867 TI - Evidence for the in vivo deamidation and isomerization of an asparaginyl residue in cytosolic serine hydroxymethyltransferase. AB - Rabbit liver cytosolic serine hydroxymethyltransferase exists in several subforms which have different isoelectric points. Incubation of the purified enzyme with chymotrypsin cleaves the enzyme at Trp14. The released amino-terminal 14-mer peptide was shown to exist in three forms of equal concentration. The peptides differ in structure only at the asparaginyl residue at position 5. In addition to asparagine at this position we found both aspartyl and isoaspartyl residues. The deamidation of Asn5 does not appear to occur during the purification of the enzyme. The in vitro rate of deamidation of Asn5 in the enzyme is more than 5 fold slower than the rate of deamidation of this residue in the free 14-mer peptide. The isoaspartyl residue at position 5 serves as a substrate for protein carboxyl methyltransferase both in the free 14-mer peptide and the native enzyme. The enzyme which has had the amino-terminal 14 residues removed by digestion with chymotrypsin still exists in several forms with different isoelectric points. Reaction of peptides from this enzyme with carboxyl methyltransferase suggests that there is at least one more asparaginyl residue in this enzyme other than Asn5 which has undergone deamidation with the formation of isoaspartyl bonds. PMID- 2318868 TI - Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. AB - The occurrence of two novel oligosaccharides in human milk was investigated. These oligosaccharides were purified by affinity chromatography on a column of an immobilized monoclonal antibody, MSW 113. Structural studies, involving 500-MHz 1H NMR spectroscopy and fast atom bombardment-mass spectrometry, indicated the structures of these compounds to be NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1 ---4) GlcNAc and NeuAc alpha 2----3Gal beta 1----3(Fuc alpha 1----4) GlcNac beta 1----3Gal. This constitutes the first evidence for the occurrence of N acetylglucosamine or galactose as the reducing-end residue of human milk oligosaccharides. These two oligosaccharides bound MSW 113 to nearly the same extent as sialyl-Lea hexasaccharide but to another sialyl-Le(a) structure directed monoclonal antibody, NS-19-9, only weakly. PMID- 2318869 TI - Elimination and reconstitution of the requirement for hormone in promoting temperature-dependent transformation of cytosolic glucocorticoid receptors to the DNA-binding state. AB - Cytosols contain a heat-stable, chelatable, anionic, molybdate-like factor that stabilizes glucocorticoid receptors in a heteromeric complex with hsp90 (refers to the 90-kDa heat shock protein) and inhibits their transformation to the DNA binding state (Meshinchi, S., Grippo, J.F., Sanchez, E.R., Bresnick, E.H., and Pratt, W.B. (1988) J. Biol. Chem. 263, 16809-16817). In this work, we demonstrate that removal of this factor by passage of L cell cytosol through the metal chelating resin Chelex-100 makes the glucocorticoid receptor unstable, thus markedly facilitating both its dissociation from hsp90 and its transformation to the DNA-binding state. In normal cytosol, both temperature-mediated dissociation of hsp90 and temperature-mediated receptor transformation are hormone-dependent events. In the Chelex-treated, metal-depleted cytosol, however, temperature mediated dissociation of hsp90 and receptor transformation occur very rapidly in a manner that is no longer hormone-dependent. When boiled L cell cytosol is added to the metal-depleted receptor system, the hormone dependence of both temperature mediated dissociation of receptor from hsp90 and receptor transformation to the DNA-binding state is reconstituted. Like boiled cytosol, molybdate stabilizes the receptor complex and inhibits its transformation in metal-depleted cytosol, but it does not reconstitute the hormone dependence of the system. These results support the proposal that an endogenous metal anion interacts with the glucocorticoid receptor to stabilize it in the heteromeric, inactive, non-DNA binding state in cytosol and that binding of the hormone promotes conversion of the receptor to the DNA-binding state through an effect on this metal anion center. PMID- 2318870 TI - Phorbol ester-induced expression of the common, low-affinity binding site for primary prostanoids in vascular smooth muscle cells. AB - We showed in an earlier study (Hanasaki, K., and Arita, H. (1989) Biochim. Biophys. Acta 1013, 28-35) that there is a common, low-affinity binding site for primary prostanoids in cultured vascular smooth muscle cells (VSMC). This site, called the "primary prostaglandin (PG) site," can be evaluated by radioreceptor assay using [3H]PGF2 alpha and [3H]PGE1. Comparison of the capacity of several PGF2 alpha analogs to displace both radioligand bindings indicated strict requirements of the 15-hydroxy group as well as the 13,14-double bond in the omega-side chain of prostaglandins for recognition of this site. Treatment of VSMC with phorbol 12-myristate 13-acetate (PMA), a known protein kinase C activator, led to concentration- and time-dependent increases in the binding activities of [3H] PGF2 alpha as well as [3H]PGE1, which could be completely suppressed by the addition of protein kinase C inhibitor, H-7. The PMA effects could be mimicked by phorbol 12,13-dibutylate, but not by inactive phorbol ester. Scatchard analyses revealed an approximately 8-fold increase in the binding density with unaltered binding affinity after PMA treatment. This expression of the primary PG site was blocked by the addition of cycloheximide and actinomycin D. In contrast, PMA did not affect the binding activity for the thromboxane A2/prostaglandin H2 receptor in VSMC. These results suggest that the expression of the primary PG site is regulated by a protein kinase C-dependent mechanism in VSMC. PMID- 2318871 TI - Affinity of lipid transfer protein for lipid and lipoprotein particles as influenced by lecithin-cholesterol acyltransferase. AB - The effects of lecithin-cholesterol acyltransferase (LCAT) on the transfer of cholesterol esters mediated by lipid transfer protein (LTP) and its affinity for lipid and lipoprotein particles were investigated. When the single bilayer vesicle preparations (containing phosphatidylcholine, cholesterol, cholesteryl ester, and apolipoprotein- (apo) A-I at the molar ratio of 90:30:1.2:0.18) or high density lipoprotein 3 (HDL3) were used as the cholesteryl ester donor and low density lipoproteins (LDL) as the acceptor, the transfer activity of LTP was enhanced by the addition of low concentrations of LCAT. In contrast, no enhancement of cholesteryl ester transfer was observed upon addition of LCAT to either the discoidal bilayer particle preparations (containing phosphatidylcholine, cholesterol, cholesteryl ester, and apo-A-I at the molar ratio of 90:30:1.2:1.0) or high density lipoprotein 2 (HDL2). Although both apo-A I and apo-A-II promoted the transfer of cholesteryl ester from vesicles to LDL, the additional enhancement of the transfer by LCAT was observed only with the vesicles containing apo-A-I. Gel permeation chromatography of LTP/vesicle and LTP/HDL3 mixtures in the presence and absence of LCAT showed that the affinity of LTP for both the vesicles and HDL3 increased upon addition of LCAT. In contrast, neither HDL2 nor discoidal bilayer particles showed any significant enhancement of LTP binding upon addition of LCAT. By using LCAT covalently bound to Sepharose 4B, a maximal interaction between LTP and bound LCAT was shown to occur at the ionic strength of 0.16. Deviation from this ionic strength reduced the extent of the interaction. At the ionic strength of 0.01 and 0.5, the elution volume of LTP was identical to that of bovine serum albumin. PMID- 2318872 TI - Isolation and expression of a human ornithine decarboxylase gene. AB - We have isolated a human ornithine decarboxylase (ODC) gene from a leukocyte genomic DNA library in order to examine the mechanisms involved in the regulation of ODC gene expression in normal and neoplastic cell growth. Nucleotide sequence analysis shows that the human ODC gene in clone ODC709-A2 consists of 12 exons which encode a protein identical to that inferred from a human ODC cDNA sequence. The 5' end of the gene was determined by S1 nuclease and primer extension mapping. The high G + C content and small open reading frame found in exon 1 may be pertinent to translation regulation of ODC. Conserved sequences and potential promoter elements including a TATA box, a possible CCAAT element, SP1 and AP-2 transcription factor binding sites, and cAMP response elements were identified in the 5'-flanking region. Transfection of mouse LM (tk-) cells with ODC709-A2 DNA resulted in the production of human ODC mRNA approximately 2.25 kilobases in length. Evidence that the protein synthesized from the human gene is functional is provided by "rescue" transfection of a Chinese hamster ovary mutant cell line, C55.7, which is ODC-deficient. C55.7 cells transfected with ODC709-A2 DNA expressed ODC enzyme activity and proliferated without exogenous putrescine. PMID- 2318873 TI - Amino acid sequence of rabbit skeletal muscle myosin. 50-kDa fragment of the heavy chain. AB - The amino acid sequence of the 50-kDa fragment that is released by limited tryptic digestion of the head portion of rabbit skeletal muscle myosin was determined by analysis and alignment of sets of peptides generated by digestion of the fragment at arginine or methionine residues. This fragment contains residues 205-636 of the myosin heavy chain; among the residues of particular interest in this fragment are N epsilon-trimethyllysine, one of four methyl-amino acids in myosin, and Ser-324, which is photoaffinity labeled by an ATP analogue (Mahmood, R., Elzinga, M., and Yount, R. G. (1989) Biochemistry 28, 3989-3995). Combination of this sequence with those of the 23- and 20-kDa fragments yields an 809-residue sequence that constitutes most of the heavy chain of chymotryptic S-1 of this myosin. PMID- 2318874 TI - Mechanistic investigations of the novel non-heme vanadium bromoperoxidases. Evidence for singlet oxygen production. AB - Three newly discovered non-heme bromoperoxidases isolated from marine algae were found to catalyze the production of singlet oxygen in reactions composed of the bromoperoxidase, hydrogen peroxide, and bromide. The bromoperoxidases studied were vanadium bromoperoxidase (V-BrPO) from Ascophyllum nodosum, native non-heme bromoperoxidase from Corallina vancouveriensis (which contains vanadium and iron), and the vanadium-reconstituted bromoperoxidase derivative from C. vancouveriensis. These enzyme systems generated near infrared emission, characteristic of singlet oxygen. The emission had a peak intensity near 1268 nm, was greatly increased in 2H2O-containing buffers, and was greatly decreased by the singlet oxygen quenchers, histidine and azide. The yield of singlet oxygen was approximately 80% of the theoretical yield. A unique feature of the non-heme bromoperoxidases distinct from the iron heme haloperoxidases, was the remarkable stability of the non-heme enzymes in the presence of singlet oxygen and oxidized bromine species. V-BrPO turned over multiple aliquots of 2 mM hydrogen peroxide without losing efficiency. In contrast, iron heme lactoperoxidase was completely inactivated after turnover of the first aliquot of 2 mM hydrogen peroxide, and iron heme chloroperoxidase was 50% deactivated. The profile of singlet oxygen formation by V-BrPO and the near stoichiometric yield of singlet oxygen suggest that the mechanism of singlet oxygen formation is the same as the mechanism of dioxygen formation determined by oxygen probe measurements. PMID- 2318875 TI - Concerted evolution of ruminant stomach lysozymes. Characterization of lysozyme cDNA clones from sheep and deer. AB - Contradictory evolutionary histories of ruminant lysozymes have been predicted by analysis of genomic blots (Irwin, D.M., Sidow, A., White, R., and Wilson, A.C. (1989) in The Immune Response to Structurally Defined Proteins: The Lysozyme Model (Smith-Gill, S.J., and Sercarz, E.E., eds) pp. 73-85, Adenine Press, Guilderland, NY) and sequences of cow stomach lysozyme cDNAs (Irwin, D.M., and Wilson, A.C. (1989) J. Biol. Chem. 264, 11387-11393). Genomic blots indicate that the amplification of the lysozyme gene family occurred 40-50 million years ago, while the cDNA sequences imply that the stomach genes began diverging from one another after the splitting of the deer and cow lineages, 25 million years ago. To resolve this contradiction, we characterized 111 stomach lysozyme cDNAs from two additional ruminant species: domestic sheep and axis deer. The cDNA sequences of the coding region of mature lysozyme together with the 3'-untranslated region were obtained from abomasum (true stomach) mRNA with the use of the polymerase chain reaction. The two primers for amplifying the cDNA were a lysozyme-specific primer, encoding a conserved sequence at the amino terminus of mature stomach lysozyme, and oligo(dT) as a general mRNA primer. Comparison of the cDNA sequences from these species to one another and to those of the cow revealed that different parts of the ruminant stomach lysozyme genes have had different evolutionary histories. The 3'-untranslated region has evolved in a divergent fashion since the original duplications 40-50 million years ago, supporting the genomic blot interpretation; by contrast, the coding region has evolved in a concerted fashion, that is, the multiple sequences within a species have evolved in unison. The 3'-untranslated portion of the lysozyme genes appears to have escaped from concerted evolution due to inability to initiate concerted evolution, rather than due to reduced sequence similarity. The process of concerted evolution in stomach lysozymes may have had roles both in adapting lysozyme to the stomach environment in early ruminants as well as in retarding amino acid sequence evolution in the well adapted lysozyme of modern ruminants. PMID- 2318876 TI - Heterogeneous modifications of the 114/A10 protein of interleukin-3-dependent cells are concentrated in a highly repetitive amino-terminal domain. AB - The protein 114/A10 is expressed in structurally heterogeneous forms on the surfaces of all murine hemopoietic cells that are responsive to the growth factor interleukin-3, including multipotent progenitors. Despite their structural diversity, all forms of 114/A10 appear to be expressed from a single gene that encodes a peptide with a potential transmembrane segment, three sequences with homology to epidermal growth factor, and an N-terminal domain consisting of eight perfect or near perfect tandem repeats of a 27-amino acid peptide that has a very high content of serine and threonine. Constructed cDNAs that encode deleted or hybrid forms of the 114/A10 protein have been expressed on COS cells in order to localize sites of post-translational modification. The results demonstrate that the structural diversity of 114/A10 is confined to its N-terminal repeat domain and probably arises through extensive O-linked glycosylation within each of the repeats in that domain. The highly modified N terminus of 114/A10 projects from the outer surface of the cell and could serve as a ligand for lectin-like proteins or could modulate the activities of the adjacent epidermal growth factor like domains of 114/A10. PMID- 2318877 TI - Studies of the oxidative half-reaction of anthranilate hydroxylase (deaminating) with native and modified substrates. AB - The oxidative half-reactions of anthranilate hydroxylase (EC 1.14.12.2) were examined in the presence of anthranilate and modified substrates. C(4a) Hydroperoxyflavin (C(4a)-FlOOH) and C(4a)-hydroxyflavin (C(4a)-FlOH) intermediates were detected in oxidative reactions with all substrates. Thus, the oxygenation reactions of the enzyme are similar to those of flavoprotein hydroxylases that convert phenolic compounds to catechols. These observations support a mechanism proposed for this enzyme (Powlowski, J. B., Dagley, S., Massey, V., and Ballou, D. P. (1987) J. Biol. Chem. 262, 69-74) involving nucleophilic attack of the substrate on C(4a)-FlOOH, and formation of an imine intermediate that is subsequently hydrolyzed. Anthranilate hydroxylase is therefore a typical flavoprotein hydroxylase with the added capacity of hydrolyzing imine intermediates. Fluorine substituents on the aromatic ring decreased the rate of conversion of C(4a)-FlOOH to C(4a)-FlOH, as predicted by this mechanism. Hydroxylation of 3-fluoro- and 3-methylanthranilates resulted in the formation of nonaromatic products that appeared to stabilize the C(4a)-FlOH. No evidence was found for a high extinction intermediate (intermediate II) (Entsch, B., Ballou, D. P., and Massey, V. (1976) J. Biol. Chem. 251, 2550-2563) under conditions where it was readily detected with other flavoprotein hydroxylases. It was shown that the spectra of the nonaromatic products (which are quinonoid forms) could not be summed with the spectra of C(4a)-hydroxyflavin to obtain that of a putative intermediate II, thus ruling out that explanation for previous observations of II. PMID- 2318878 TI - Inhibitors of ergosterol biosynthesis and growth of the trypanosomatid protozoan Crithidia fasciculata. AB - Six nitrogen-, sulfur- and cyclopropane-containing derivatives of cholestanol were examined as inhibitors of growth and sterol biosynthesis in the trypanosomatid protozoan Crithidia fasciculata. The concentrations of inhibitors in the culture medium required for 50% inhibition of growth were 0.32 microM for 24-thia-5 alpha,20 xi-cholestan-3 beta-ol (2), 0.009 microM for 24-methyl-24-aza 5 alpha,20 xi-cholestan-3 beta-ol (3), 0.95 microM for (20,21),(24,-25)-bis (methylene)-5 alpha,20 xi-cholestan-3 beta-ol (4), 0.13 microM for 22-aza-5 alpha,20 xi-cholestan-3 beta-ol (5), and 0.3 microM for 23-azacholestan-3-ol (7). 23-Thia-5 alpha-cholestan-3 beta-ol (6) had no effect on protozoan growth at concentrations as high as 20 microM. Ergosterol was the major sterol observed in untreated C. fasciculata, but significant amounts of ergost-7-en-3 beta-ol, ergosta-7,24(28)-dien-3 beta-ol, ergosta-5,7,22,24(28)-tetraen-e beta-ol, cholesta-8,24-dien-3 beta-ol, and, in an unusual finding, 14 alpha-methyl cholesta-8,24-dien-3 beta-ol were also present. When C. fasciculata was cultured in the presence of compounds 2 and 3, ergosterol synthesis was suppressed, and the principal sterol observed was cholesta-5,7,24-trien-3 beta-ol, a sterol which is not observed in untreated cultures. The presence of this trienol strongly suggests that 2 and 3 specifically inhibit the S-adenosylmethionine:sterol C-24 methyltransferase but do not interfere with the normal enzymatic processing of the sterol nucleus. When C. fasciculata was cultured in the presence of compounds 5 and 7, the levels of ergosterol and ergost-7-en-3 beta-ol were suppressed, but the amounts of the presumed immediate precursors of these sterols, ergosta 5,7,22,24(28)-tetraen-3 beta-ol and ergosta-7,24-(28)-dien-3 beta-ol, respectively, were correspondingly increased. These findings suggest that 5 and 7 specifically inhibit the reduction of the delta 24(28) side chain double bond. When C. fasciculata was cultured in the presence of compound 4, ergosterol synthesis was suppressed, but the sterol distribution in these cells was complex and not easily interpreted. Compound 6 had no significant effect on sterol synthesis in C. fasciculata. PMID- 2318879 TI - Two lectin genes differentially expressed in Dolichos biflorus differ primarily by a 116-base pair sequence in their 5' flanking regions. AB - Previous studies in our laboratory have shown that the Dolichos biflorus plant contains two similar lectins, a seed lectin and a stem and leaf lectin called DB58, that are present at different stages in the plant's life cycle. We have now established that each of these lectins is encoded by a separate gene by isolating these lectin genes from a library of D. biflorus nuclear DNA. Restriction mapping and nucleotide sequencing analyses show that the seed lectin and DB58 genes are located in the same transcriptional orientation within 3-kilobase pairs of one another. The lectin genes contain no introns and show greater than 90% nucleotide sequence identity in their protein coding and untranslated regions. This sequence similarity extends to both the 5' and 3' flanking regions of the genes; the major exception is that a 116-base pair segment located at position -215 to -100 from the transcription start site of the seed lectin gene is missing in the 5' flanking region of the DB58 gene. The possible significance of this segment with respect to the differential expression of these genes is discussed. PMID- 2318880 TI - The cDNA sequence of mouse LAMP-2. Evidence for two classes of lysosomal membrane glycoproteins. AB - We describe the isolation and sequencing of a cDNA encoding the mouse lysosomal membrane glycoprotein mLAMP-2 and the sequence differences that distinguish this molecule from the LAMP-1 class of proteins. An oligonucleotide probe corresponding to the NH2-terminal amino acid sequence of purified mLAMP-2 was synthesized by the polymerase chain reaction and used to screen several cDNA libraries. cDNA clones with an insert of 1,700 nucleotides were identified and sequenced. The deduced amino acid sequence of mLAMP-2 comprises a signal sequence of 25 residues and a 390-amino acid polypeptide (Mr 43,017) with the following putative domains: a large intraluminal region (residues 1-354) with 17 N-linked glycosylation sites (Asn-X-Ser/Thr), a hydrophobic transmembrane-spanning region of 24 residues (355-378), and a COOH-terminal cytoplasmic tail of 12 residues (379-390). When this sequence is compared with those of other lysosomal membrane glycoproteins, it is apparent that mouse LAMP-2 and human LAMP-2 form one homology class (LAMP-2) that is separated from the LAMP-1 class of proteins. The sequence differences in these two classes provide a basis for comparing the structure of the proteins with their biochemical and biological properties. PMID- 2318881 TI - The transcription complex of the 5 S RNA gene, but not transcription factor IIIA alone, prevents nucleosomal repression of transcription. AB - Assembly of nucleosomes on a 5 S DNA plasmid with histone H3.H4-N1 complex and histone H2A-H2B dimers causes a marked, 30-300-fold repression of 5 S RNA transcription. This repression is a time-dependent process that parallels the process of nucleosome formation. At physiological histone levels, DNA plasmids carrying nucleosomes with only histones H3 and H4 are transcriptionally permissive. The histone H3-H4 chromatin becomes transcriptionally nonpermissive when histone H2A-H2B dimers complement the nucleosome assembly reaction. H3-H4 H2A-H2B nucleosomes, but not H3-H4 nucleosomes, displace a DNA-bound transcription factor IIIA. In contrast, a preassembled 5 S RNA transcription complex is refractory to inactivation by nucleosomes. PMID- 2318882 TI - Ligand-induced biphasic protein denaturation. AB - The results of a thermodynamic calculation of the excess heat capacity that is based on experimental observations and that incorporates the effects of ligand binding on the two-state, thermal denaturation of a protein are presented. For a protein with a single-binding site on the native species and at subsaturating concentrations of ligand, bimodal or unimodal thermograms were computed merely by assuming a larger or smaller ligand association constant, respectively. The calculated thermograms for this simplified case show the salient features of those observed by differential scanning calorimetry for defatted human albumin monomer in the absence and presence of three ligands for which the protein has higher, intermediate, and lower affinity (Shrake, A., and Ross, P. D. (1988) J. Biol. Chem. 263, 15392-15399). The computation demonstrates that biphasic unfolding can result from a significant increase in the free energy of denaturation (and the transition temperature) during the course of unfolding due to a substantial increase in free ligand concentration caused by the release of bound ligand by denaturing protein. Such ligand-induced biphasic denaturation does not relate to macromolecular substructure but derives from a perturbation, during unfolding, of the ligand binding equilibrium, which is coupled to the equilibrium between the folded and unfolded protein species. Thus, this bimodality is not limited to thermally induced unfolding but is operative independent of the means used to effect denaturation and therefore must be considered when studying any macromolecular folding/unfolding reaction in the presence of ligand. PMID- 2318883 TI - Casein kinase II from Caenorhabditis elegans. Properties and developmental regulation of the enzyme; cloning and sequence analyses of cDNA and the gene for the catalytic subunit. AB - The nematode Caenorhabditis elegans provides a model system for investigating the structure, function, and regulation of casein kinase II. Cytosols from C. elegans embryos and gravid adults, which contain fertilized eggs and embryos, are enriched in casein kinase II activity; cytosols from newly hatched larva, four subsequent larval stages, and immature adults exhibit casein kinase II levels that are 3-10-fold lower than those observed in embryo cytosol. C. elegans casein kinase II contains alpha (Mr = 42,000) and beta (Mr = 29,000) subunits and has a Stokes radius of 50 nm. The enzyme utilizes ATP and GTP as substrates, is potently inhibited by heparin and undergoes autophosphorylation. Sequence analyses of cloned cDNAs corresponding to the 1.7-kilobase mRNA encoding the alpha (catalytic) subunit of casein kinase II indicate that the alpha polypeptide contains 359 amino acid residues. Variations in the abundance of casein kinase II alpha mRNA are coordinated with changes in enzyme activity during C. elegans development, indicating that alpha subunit expression is controlled at a pretranslational level. However, the magnitude of the developmentally controlled changes in phosphotransferase activity exceeded the corresponding increments in alpha subunit mRNA content. This suggests that translational and/or post translational mechanisms also play an important role in the developmental regulation of C. elegans casein kinase II activity. The 2.9-kilobase casein kinase II alpha gene is divided into eight exons by intervening sequences ranging from 48 to 457 base pairs in length. The alpha gene promoter contains a TATA box, and a unique transcription start site has been identified. The intron/exon organization of the casein kinase II alpha gene differs markedly from the gene structure of the catalytic subunit of murine cAMP-dependent protein kinase (Chrivia, J. C., Uhler, M. D., and McKnight, G. S. (1988) J. Biol. Chem. 263, 5739-5744). PMID- 2318884 TI - Purified Drosophila transcription factor, Adh distal factor-1 (Adf-1), binds to sites in several Drosophila promoters and activates transcription. AB - Adh distal factor-1 (Adf-1) is a sequence-specific DNA-binding activity originally identified in Drosophila tissue culture cells and embryos. Adf-1 binds to upstream recognition elements in each of the two promoters of the Drosophila alcohol dehydrogenase gene (Adh), and binding of Adf-1 to the Adh distal promoter site activates transcription. We have carried out a mutational analysis of the Adh distal promoter using both an in vitro transcription assay and a transient transfection assay in Drosophila tissue culture cells, and in both cases find that deletion of sequences required for Adf-1 binding leads to a 3-4-fold drop in transcription. We have purified Adf-1 and demonstrate by a sodium dodecyl sulfate gel renaturation assay that it is a 34-kDa protein. Purified Adf-1 activates Adh distal promoter transcription in vitro in a binding site-dependent manner. DNase I footprint analysis shows that the purified protein binds not only to the two previously characterized sites in Adh but also to transcriptional regulatory elements in the dopa decarboxylase (Ddc) and Antennapedia (Antp) P1 promoters. Thus, it appears that Adf-1 may play an important role not only in the regulation of Adh expression but also in the transcription of other Drosophila genes as well. PMID- 2318885 TI - Expression of cloned human reticulocyte 15-lipoxygenase and immunological evidence that 15-lipoxygenases of different cell types are related. AB - Cloned 15-lipoxygenase has been expressed for the first time in eukaryotic and prokaryotic cells. Transfection of osteosarcoma cells with a mammalian expression plasmid containing the cDNA for human reticulocyte 15-lipoxygenase resulted in cell lines that were capable of oxidizing body arachidonic acid and linoleic acid. The lipoxygenase metabolites were identified by reverse-phase and straight phase high pressure liquid chromatography, ultraviolet spectroscopy, and direct mass spectrometry, verifying that the cDNA for 15-lipoxygenase encodes an enzyme with authentic 15-lipoxygenase activity. Incubation of the transformed cells with arachidonic acid generated 15-hydroxyeicosatetraenoic acid (HETE) and 12-HETE in a ratio of 8.6 to 1, demonstrating that 15-lipoxygenase can also perform 12 lipoxygenation. Lesser amounts of 15-keto-ETE, four isomers of 8,15-diHETE, and one isomer of 14,15-diHETE were observed. Incubation with linoleic acid generated predominantly 13-hydroxy linoleic acid. The reaction was inhibited by eicosatetraynoic acid but not by indomethacin. Antibodies to a peptide corresponding to a unique region of the predicted amino acid sequence were generated and shown to react with one major band of 70 kDa on immunoblots of human leukocyte 15-lipoxygenase. To obtain antibodies to the full length enzyme, the cDNA was subcloned into a bacterial expression vector and was expressed as a fusion with the CheY protein. The overexpressed protein was readily purified from bacteria and was shown to be immunoreactive to the peptide-derived antibody. Antibodies raised to this recombinant enzyme did not cross-react with human leukocyte 5-lipoxygenase but did identify 15-lipoxygenase in rabbit reticulocytes, human leukocytes, and tracheal epithelial cells, suggesting that the 15-lipoxygenases from these different cell types are structurally related. PMID- 2318886 TI - Regulation of in vitro transcription by progesterone receptor. Characterization and kinetic studies. AB - We have devised an in vitro assay system to study the transcriptional activity of native chicken progesterone receptor (cPR). Purified cPR added to cell-free extracts from HeLa cell nuclei stimulates accurate transcription from a promoter driven by two progesterone response elements. The transcriptional enhancement is entirely progesterone response element dependent and promoter specific. We have defined the appropriate conditions of template, nuclear extract, salt, and magnesium ion requirements for efficient transcriptional enhancement by cPR. Under optimized conditions, a synthesis rate of one transcript/20 promoters is achieved in the presence of saturating amounts of cPR. Kinetic studies suggest that the progesterone receptor can form a functional preinitiation complex with RNA polymerase II and other transcription factors present in unfractionated HeLa nuclear extract. Following formation of this complex, transcription can commence rapidly upon addition of nucleotides. PMID- 2318887 TI - Purification of protein fatty acyltransferase and determination of its distribution and topology. AB - Studies reported from this laboratory have demonstrated that O-glycosidic glycoproteins of salivary, pulmonary, and gastrointestinal origin are acylated by fatty acyltransferase residing in Golgi and microsome-enriched fraction (Slomiany, A., Liau, Y.H., Takagi, A., Laszewicz, W., and Slomiany, B.L. (1984) J. Biol. Chem. 259, 13304-13308). Here we report on the successful purification of this enzyme from rough microsomal membranes of rat gastric mucosa and its identification in a number of diverse tissues and organs, such as heart, liver, pancreas, lung, kidney, salivary glands, and lymphoblasts. The enzymatic activity has been released from the stripped and salt-extracted microsomes with 0.5% Triton X-100 and recovered from 100,000 x g supernatant by affinity chromatography on Cibacron blue F3GA column. The retained fatty acyltransferase protein was selectively displaced from the column with 50 microM palmitoyl-CoA. On nonreducing polyacrylamide gel electrophoresis, the enzymatic activity was associated with a 234-kDa complex, and on sodium dodecyl sulfate polyacrylamide gel electrophoresis, the complex afforded 65- and 67-kDa protein bands. Incubation of microsomes with trypsin prior to enzyme extraction resulted in a 50% inactivation of the fatty acyltransferase and generation of 53- and 55-kDa protein bands, which also had affinity to Cibacron blue F3GA and were displaced from the column together with the active (intact) enzyme. We suggest that the fatty acyltransferase is an integral rough microsomal protein partially exposed to cytosol, which catalyzes the fatty acyl-CoA-protein reaction on the cytosolic site of the rough endoplasmic reticulum and that this enzyme is responsible for processing of the group of protein which are entering rough endoplasmic reticulum Golgi secretory pathway. PMID- 2318888 TI - Histone acetylation alters the capacity of the H1 histones to condense transcriptionally active/competent chromatin. AB - The relationship between histone acetylation and the capacity of H1 histones to cause the 0.15 M NaCl-induced aggregation/precipitation of transcriptionally active/competent gene chromatin fragments was investigated. Previous studies have shown that transcriptionally active/competent, but not repressed, gene chromatin polynucleosomes, which were isolated from chicken erythrocytes, remained soluble in 0.15 M NaCl after being reconstituted with H1 histones. This result suggested that some component of the active/competent gene nucleosome altered the capacity of the H1 histones to condense the chromatin fiber. Recently, Hebbes et al. (Hebbes, T.R., Thorne, A.W., and Crane-Robinson, C. (1988) EMBO J. 7, 1395-1402) demonstrated directly that active, but not repressed, gene chromatin of chicken erythroid cells contain high levels of acetylated histones. Here, we show that the solubility of active/competent gene chromatin fragments in 0.15 M NaCl is dependent on the level of acetylated histone species, with induction of hyperacetylation increasing the solubility of this gene chromatin. Also, we show that lowering the levels of the acetylated histone forms reduces the ability of the active/competent gene chromatin fragments to resist exogenously added H1 histone-induced 0.15 M NaCl aggregation/precipitation. These results suggest that histone acetylation alters the capacity of the H1 histones to form compact higher order chromatin structures such that active/competent gene chromatin is maintained in a less folded state than the bulk of chromatin. PMID- 2318890 TI - Scavenger receptor-mediated uptake and metabolism of lipid vesicles containing acidic phospholipids by mouse peritoneal macrophages. AB - We studied the mechanism of uptake and metabolism of exogenous phospholipids in mouse peritoneal macrophages using vesicles composed of various phospholipids and cholesterol. Macrophages in culture were found to actively incorporate and metabolize phosphatidylcholine/cholesterol vesicles containing small amounts of acidic phospholipids such as phosphatidylserine, phosphatidylinositol, or phosphatidic acid and to store the fatty acyl chains and cholesterol in triacylglycerol and cholesteryl ester form in their cytosol. These cells exhibited massive amounts of oil red O-positive lipid droplets, a typical feature of foam cells. The metabolism of exogenous phospholipid vesicles was completely inhibited by chloroquine and cytochalasin B, suggesting that vesicle uptake occurs by endocytosis. A similar type of metabolism was observed in guinea pig peritoneal macrophages, macrophage cell line J774.1, but not in Swiss 3T3 fibroblasts. Competition studies using various ligands for the scavenger receptor showed that acetylated low density lipoprotein (acetyl-LDL), dextran sulfate, or fucoidan was able to compete for up to 60% of the binding of phosphatidylserine containing vesicles, and that copper-oxidized LDL (oxidized LDL) competed for more than 90% of the vesicle binding. On the other hand, phosphatidylserine containing vesicles was able to compete for more than 90% of the binding of acetyl-LDL. These results indicate that acidic phospholipids are recognized by the scavenger receptors on the surface of macrophages and that more than one scavenger receptor exists on mouse peritoneal macrophages, i.e. one capable of recognizing acetyl-LDL, oxidized LDL, and an array of acidic phospholipids on membranes, and the other recognizing both acidic phospholipids and oxidized LDL but not acetyl-LDL. PMID- 2318889 TI - On the activation of human leuserpin-2, a thrombin inhibitor, by glycosaminoglycans. AB - Human leuserpin-2 (hLS2) cDNA variants generated by site-directed mutagenesis were expressed in a transient COS cell system. Functional analysis of the mutants revealed two regions in the NH2-terminal half of hLS2 which are essential for glycosaminoglycan-enhanced thrombin inhibition by hLS2. One of these regions, which encompasses a dimeric structure enriched in basic amino acids, is required for both glycosaminoglycan binding and glycosaminoglycan-mediated acceleration of thrombin inhibition. Deletion of another dimeric region, which spans a sequence with a high negative charge density, resulted in a strong reduction in the glycosaminoglycan-enhanced activity of hLS2. This polyanionic region displays structural and functional similarities to the COOH-terminal end of hirudin, another potent thrombin inhibitor, indicating that both inhibitors may have a common binding site on thrombin. Based on our observations we propose a model for the activation of hLS2 by glycosaminoglycans. The key feature of this model is the suggestion that the glycosaminoglycan-enhanced reaction between hLS2 and thrombin is mediated by at least two regions of contact, involving both the reactive center region and the acidic domain of hLS2. Binding of glycosaminoglycans to hLS2 is suggested to result first in the release of the acidic region from intramolecular interactions. Then, amino acid sequences in thrombin are proposed to interact with the acidic dimer of hLS2. PMID- 2318891 TI - Characterization of the deoxyribonuclease activity of diphtheria toxin. AB - Having discovered that the A domain of diphtheria toxin exhibits intrinsic nuclease activity (Chang, M. P., Baldwin, R. L., Bruce, B., and Wisnieski, B. J. (1989) Science 246, 1165-1168), we proceeded to examine the requirements for optimal enzymic expression. In vitro assays with linear double-stranded DNA demonstrated that optimal activity occurs at pH 7.5 and 37 degrees C. A characterization of the stringent cation-dependence of the reaction revealed increasing activity with increasing Mn2+ up to 30 mM. In contrast, activity levels with Ca2+ or Zn2+ alone peaked at 100 microM and with Mg2+ alone at 1 mM. The Zn2(+)- and Mg2(+)-stimulated activities appear to be dependent on trace amounts of Ca2+. Indeed, inclusion of 2 mM Ca2+ plus 3 mM Mg2+ in the reaction buffer promoted a high level of DNA cleavage even though very little cleavage was seen with either cation alone at 2-3 mM. Addition of 20-200 mM NaCl or KCl caused progressive inhibition. Detection of diphtheria toxin nuclease activity under physiologically relevant conditions suggests that it may be operative in vivo and supports our contention that diphtheria toxin-induced cytolysis is not a simple consequence of protein synthesis inhibition, but rather the final step in a cytolytic pathway linked to chromosomal integrity. PMID- 2318892 TI - Muscle-type MM creatine kinase is specifically bound to sarcoplasmic reticulum and can support Ca2+ uptake and regulate local ATP/ADP ratios. AB - Highly purified fractions of sarcoplasmic reticulum (SR) were prepared from chicken pectoralis muscles (Saito, A., Seiler, S., Chu, A., and Fleischer, S. (1984) J. Cell Biol. 99, 875-885) and analyzed for the presence of creatine kinase (CK). Vesicles derived from longitudinal SR contained 0.703 +/- 0.428 IU of CK/mg of (SR) protein. Immunogold localization of muscle-type MM-CK on ultrathin cryosections of muscle, after removal of soluble CK, revealed relatively strong in situ labeling of M-CK remaining bound to the M band as well as to the SR membranes. In addition, purified SR vesicles were also labeled by anti-M-CK antibodies, and the peripheral labeling was similar to that observed with anti-Ca2(+)-ATPase antibodies. Only some particulate CK enzyme was released from isolated SR membranes by EDTA/low salt buffer, and CK was resistant to extraction by 0.6 M KCl. Thus, some of the MM-CK present in muscle displays strong associative behavior to the SR membranes. The SR-bound CK was sufficient to support, in the presence of phosphocreatine plus ADP, a significant portion of the maximal in vitro Ca2+ uptake rate. The ATP regeneration potential of SR-bound CK was similar to the rate of Ca2(+)-stimulated ATP hydrolysis of isolated SR vesicles. Thus, CK bound to SR may be physiologically relevant in vivo for regeneration of ATP used by the Ca2(+)-ATPase, as well as for regulation of local ATP/ADP ratios in the proximity of the Ca2+ pump and of other ATP-requiring reactions in the excitation-contraction coupling pathway. PMID- 2318893 TI - A newly identified iron binding protein in duodenal mucosa of rats. Purification and characterization of mobilferrin. AB - An iron binding protein with an approximate molecular mass of 56,000 daltons was purified to homogeneity from homogenates of rat duodenal mucosa. The protein was biochemically and immunologically distinct from transferrin and ferritin and competitively bound cobalt, copper, zinc, and lead. Each molecule bound one molecule of iron with a Kd of 9 X 10(-5). Dissociation of iron and the protein was accelerated at acid pH. Using an immunogold method, the protein was identified in the apical cytoplasm of proximal small intestinal cells and was not observed elsewhere in the intestinal mucosa and in other body organs. It was named mobilferrin from its city of origin and to differentiate it from other previously identified iron binding proteins. PMID- 2318894 TI - A rat osteogenic cell line (UMR 106-01) synthesizes a highly sulfated form of bone sialoprotein. AB - The rat osteosarcoma cell line (UMR 106-01) synthesizes and secretes relatively large amounts of a sulfated glycoprotein into its culture medium (approximately 240 ng/10(6) cells/day). This glycoprotein was purified, and amino-terminal sequence analysis identified it as bone sialoprotein (BSP). [35S]Sulfate, [3H]glucosamine, and [3H]tyrosine were used as metabolic precursors to label the BSP. Sulfate esters were found on N- and O-linked oligosaccharides and on tyrosine residues, with about half of the total tyrosines in the BSP being sulfated. The proportion of 35S activity in tyrosine-O-sulfate (approximately 70%) was greater than that in N-linked (approximately 20%) and O-linked (approximately 10%) oligosaccharides. From the deduced amino acid sequence for rat BSP (Oldberg, A., Franzen, A., and Heinegard, D. (1988) J. Biol. Chem. 263, 19430-19432), the results indicate that on average approximately 12 tyrosine residues, approximately 3 N-linked, and approximately 2 O-linked oligosaccharides are sulfated/molecule. The carboxyl-terminal quarter of the BSP probably contains most, if not all, of the sulfated tyrosine residues because this region of the polypeptide contains the necessary requirements for tyrosine sulfation. Oligosaccharide analyses indicated that for every N-linked oligosaccharide on the BSP, there are also approximately 2 hexa-, approximately 5 tetra-, and approximately 2 trisaccharides O-linked to serine and threonine residues. On average, the BSP synthesized by UMR 106-01 cells would contain a total of approximately 3 N-linked and approximately 25 of the above O-linked oligosaccharides. This large number of oligosaccharides is in agreement with the known carbohydrate content (approximately 50%) of the BSP. PMID- 2318895 TI - Glucose phosphorylation. Interaction of a 50-amino acid peptide of yeast hexokinase with trinitrophenyl ATP. AB - A 50-amino acid peptide predicted by chemical modification studies of yeast hexokinase to contain an ATP-binding site has been synthesized and purified. The peptide, which includes residues from glutamate 78 at the NH2-terminal end to leucine 127 at the COOH-terminal, resides within the smaller of the two lobes found in the three-dimensional structure of yeast hexokinase. It is this region which has been reported recently to exhibit significant sequence homology with hexokinase types I and IV of higher eukaryotic cells and sequence homology with the active site of protein kinases. Similar to native yeast hexokinase, the 50 amino acid peptide interacts strongly with the fluorescent analog TNP-ATP [2',(3')-O-(2,4,6-trinitrophenyl)-adenosine-5'-triphosphate]. A 5-fold enhancement is observed when 8 microM peptide interacts with 20 microM TNP-ATP. The stoichiometry of binding is very close to 1 mol of TNP-ATP/mol peptide. Also, similar to native yeast hexokinase, the fluorescent enhancement observed upon TNP ATP binding to the synthetic peptide is greater than that observed upon TNP-ADP binding. Finally, TNP-AMP exhibits a much lower fluorescent enhancement in the presence of hexokinase or the synthetic peptide. The additional findings that ATP can readily prevent TNP-ATP binding and that TNP-ATP can substitute for ATP as a weak substrate for hexokinase in the phosphorylation of glucose indicate that the synthetic peptide described here comprises part of the catalytic site. PMID- 2318896 TI - Tissue/biomaterial interface characteristics of four elastomers. A transmission electron microscopical study. AB - The tissue/biomaterial interface reactions of four elastomers--selected as candidates for scaffolding for tympanic membrane tissue in a total alloplastic middle ear prosthesis--were studied at the electron microscopical level after implantation in the rat middle ear. Time-dependent changes in the phagocyte/polymer interface suggested degradation of porous implants made of Estane polyether urethane, polypropylene oxide, and a poly(ethylene oxide hydantoin) and poly(tetramethylene terephthalate) segmented polyether polyester copolymer (HPOE/PBT copolymer), but not of dense Silastic silicone rubber implants. Silastic was always encapsulated in fibrous tissue. Contact between fibrous tissue and HPOE/PBT copolymer or Estane was established in the third month, but fibrous tissue was never seen close to polypropylene oxide. Bone made contact only with Estane and HPOE/PBT copolymer implants. The bone/copolymer interface showed an electron-dense layer morphologically similar to that seen between bone and hydroxyapatite ceramic, suggesting that with respect to bone HPOE/PBT copolymer behaves like a bioactive implant material. The electron-dense layer was absnet at the bone/Estane interface. Estane and especially HPOE/PBT copolymer seem to be suitable as alloplastic tympanic membrane because of their interface behavior with respect to fibrous tissue and bone. PMID- 2318897 TI - Tissue response to percutaneous implants in rabbits. AB - This study reports on certain aspects of wound-healing around percutaneous implants. Plasma-sprayed and dense hydroxylapatite, titanium, and carbon test implants were inserted into the tibia and the cranium of 12 rabbits. Four and 8 months after insertion, the animals were sacrificed and the implants with their surrounding tissues were processed histologically. Light- and transmission electron microscopic investigations were performed. It is found that direct and indirect bone-anchoring favors the longevity of percutaneous implants. No differences in tissue reaction between the various implant materials were observed. PMID- 2318898 TI - Surface modification of biomaterials through noble metal ion implantation. AB - Studies are described involving effects of noble-metal ion implantation on corrosion inhibition and charge-injection capabilities of surgical Ti-6A1-4V alloy. A major factor linked to excellent long-term biological performance is resistance to metal-ion release to tissues. The elements most resistant to corrosion in aqueous solutions are the noble metals. Disadvantages include expense and general inadequacy of mechanical properties. However, if small quantities can be used to surface-modify a surgical device in the last stage of manufacture, that device could possess an optimum combination of environmental integrity, biological response, mechanical properties, and charge-injection capability at minimum expense. Results for ion-implanted Ir are presented. Iridium has been described as the most corrosion-resistant element known, and its activated oxide as having the highest charge-injection capability of any material known. Ti-6A1-4V samples, ion implanted with 2.5 and 5.0 atomic % peak-maximum concentrations of Ir, were subjected to corrosion treatments to enrich the surface with Ir. Corrosion potential and cyclic voltammetry measurements indicated enrichment in H2SO4, and continued enrichment in isotonic saline, with corrosion potentials approaching that of pure Ir, and charge densities in isotonic saline exceeding that of pure Ir for the 5.0% peak-max Ir implanted material. X-ray photoelectron spectroscopy confirmed the high levels of Ir surface enrichment. PMID- 2318899 TI - Effect of alternative crosslinking methods on the low strain rate viscoelastic properties of bovine pericardial bioprosthetic material. AB - Early failures of bovine pericardial heart valves have been due to leaflet perforation/tearing and calcification. Since glutaraldehyde fixation has been shown to produce marked changes in leaflet mechanics and has been linked to the development of calcification, alternative crosslinking techniques have been suggested as means to overcome these obstacles. We have examined the low strain rate viscoelastic behavior of bovine pericardium: (1) fresh; (2) chemically treated with glutaraldehyde, cyanimide, or polyglycidyl ether; or (3) physically treated by freeze-drying or heat-drying. Shrinkage temperature tests were conducted to assess intrahelical crosslinking. Polyglycidyl ether and glutaraldehyde both produced substantial crosslinking, with the shrinkage temperature rising above 80 degrees C. Mechanical changes were nearly equivalent, both showing decreased stress relaxation and increased extensibility consistent with intrahelical crosslinking and shrinkage during fixation. Cyanimide, known to crosslink pure collagen materials, showed no evidence of crosslinking intact tissue. Heat-drying, also effective in pure collagen preparations, produced an increase in UTS and tissue modulus, but otherwise left the tissue unchanged. Freeze-drying had no mechanical effect, and therefore provides an attractive means for the storage of connective tissues for later mechanical testing. PMID- 2318900 TI - Cytotoxicity testing of wound dressings using normal human keratinocytes in culture. AB - Comparative cytotoxicity testing of 16 wound dressings of different composition show that normal human keratinocytes (NHK) growing on a fibroblastic feeder layer are as sensitive to toxic materials by direct contact as the confluent MRC5 fibroblasts used for standard cell culture cytotoxicity testing, and slightly more sensitive when extracts of the dressings were tested. After direct contact with each of the cell types, we found effects due to 12 dressing samples (75%), but the extracts of only 6 of them induced changes in cell shape or cell death on NHK, and 4 of them on MRC5 cells. In order to assess the compatibility of these dressings with a pure population of epidermal cells, the cell type responsible for reepidermization of healing wounds, we then tested the sensitivity, both to dressing samples and extracts, of normal human keratinocytes (NHK) grown in chemically defined medium and without a feeder layer: The results show epidermal cytocompatibility of 10 dressing extracts, while 6 others induced cytopathic effects. Three of these extracts specifically damaged epidermal cells and inhibited their proliferation. When comparing the sensitivities of NHK (in defined medium) and MRC5 cells, we observed complete correlation for 75% of the dressings by extract testing and in 94% of the cases after direct contact. PMID- 2318901 TI - Macroporous calcium phosphate ceramic for long bone surgery in humans and dogs. Clinical and histological study. AB - Our previous studies reported the performance of Macroporous Biphasic Calcium Phosphate (MBCP) in spine fusion. In the present study, this material was used in block forms in selected patients with tumoral resection in long bone. Two cases were chosen with large benign bone tumors. Clinical and radiographic assessments, CT scans, and NMR were performed after 16 months, and in one case control biopsies were taken. In order to understand the kinetic process of biodegradation of the MBCP blocks and bone formation at the expense of the ceramics, an experimental study in surgically created bond defects in canine femoral cortices was made. The MBCP blocks recovered after implantation period from 2 to 18 weeks were analyzed using histological, stereological, ultrastructural, electron microprobe, and IR spectroscopy analyses. This study demonstrated the efficiency of MBCP blocks for filling pathological defects in human long bone. The biointegration process of the MBCP blocks was due to a partial dissolution of the ceramics crystals (b-TCP content) by multinucleated cells. Simultaneously, bone ingrowth at the expense of the ceramic is observed. The new bone formation inside the MBCP macropores and in the spaces between the blocks, involved the formation of a new cortical bone on the outer part, and a trabecularlike bone with bone marrow in the inner part of the implant. The biological resorption of the MBCP ceramic decreased after 1 month implantation in dog, due to the protective role of the newly formed lamellar bone on the surface and in the core of the ceramics. PMID- 2318902 TI - Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells. I. Biochemical and immunocytochemical features. AB - Cytoskeletal abnormalities occurring during oxidative stress generated by the metabolism of the redox cycling compound 2-methyl-1,4-naphtoquinone (menadione) have been investigated in different mammalian cells in culture. Extraction of the whole cytoskeleton as well as the intermediate filament- and the microtubule enriched fractions from menadione-treated cells revealed a marked depletion of protein sulfhydryl groups. The analysis of the whole cytoskeletal fraction by PAGE showed a menadione-dependent and thiol-sensitive oxidation of actin, leading to the formation of high-molecular-weight aggregates. In addition, the extraction of this fraction with high concentrations of KCl entailed only a partial solubilization of actin. The comparative cytochemical analysis performed on treated cells showed a menadione-dependent clustering of actin microfilaments. The metabolism of menadione induced microtubule depolymerization and inhibition of GTP-induced microtubule assembly from soluble cytosolic components. The latter phenomenon was prevented by previously treating the cytosolic fraction with thiol reductants such as dithiothreitol. Menadione increased the protein content of the intermediate-size filament fraction, partially purified by one or more cycles of disassembly/assembly, and particularly enriched in polypeptides reacting with antikeratin antibodies. Furthermore, a reversible and oxidation-dependent change of the electrophoretic mobility of some polypeptides in this fraction was detected. The immunocytochemical investigation of intermediate-size filament distribution in menadione-treated cells, however, revealed only minor modifications mainly consisting of perinuclear condensation of cytokeratin structures. These findings suggest that cytoskeletal structures (actin microfilaments, microtubules, and intermediate-size filaments) are actually significant targets in quinone-induced oxidative stress. PMID- 2318903 TI - Distinct genomic copy number in mitochondria of different mammalian organs. AB - This study shows that mitochondria in liver, kidney, heart, and brain of the mouse have a distinct mitochondrial density. It also demonstrates that the mtDNA copy number per mitochondrion is organ-specific. A reliable method of determining mitochondrial density per organ is by stereological analysis of tissue sections while mtDNA quantitation is by the use of radiolabelled mtDNA probe. This is the first study in which a comprehensive examination of mitochondrial density and quantitation of mitochondrial genomes in mouse organs have been done. In summary the variability is not only in mitochondrial density but also in genomic copy number in mitochondria of various tissues. PMID- 2318904 TI - Growth-associated modifications of low-molecular-weight thiols and protein sulfhydryls in human bronchial fibroblasts. AB - The thiol redox status of cultured human bronchial fibroblasts has been characterized at various growth conditions using thiol-reactive monobromobimane, with or without the combination of dithiotreitol, a strong reducing agent. This procedure has enabled measurement of the cellular content of reduced glutathione (GSH), total glutathione equivalents, cysteine, total cysteine equivalents, protein sulfhydryls, protein disulfides, and mixed disulfides. Passage of cells with trypsin perturbs the cellular thiol homeostasis and causes a 50% decrease in the GSH content, whereas the total cysteine content is subsequently increased severalfold during cell attachment. During subsequent culture, transient severalfold increased levels of GSH, protein-bound thiols, and protein disulfides are reached, whereas the total cysteine content gradually declines. These changes in the redox balance of both low-molecular-weight thiols and protein-bound thiols correlate with cell proliferation and mostly precede the major growth phase. When the onset of proliferation is inhibited by maintenance of cells in medium containing decreased amounts of serum, the GSH content remains significantly increased. Subsequent stimulation of growth by addition of serum results in decreased GSH levels at the onset of proliferation. In thiol-depleted medium, proliferation is also inhibited, whereas GSH levels are increased to a lesser extent than in complete medium. Exposure to buthionine sulfoximine inhibits growth, prevents GSH synthesis, and results in accumulation of total cysteine, protein-bound cysteine, and protein disulfides. For extracellular cystine, variable rates of cellular uptake correlate with the initial increase in the total cysteine content observed following subculture and with the GSH peak that precedes active proliferation. The results strongly suggest that specific fluctuations in the cellular redox balance of both free low-molecular-weight thiols and protein sulfhydryls are involved in growth regulation of normal human fibroblasts. PMID- 2318905 TI - Signal perception of fibroblasts for directional migration to platelet-derived growth factor in Boyden-type chambers. AB - Fibroblast chemotaxis has usually been determined in Boyden-type chambers with polycarbonate filters, assuming that a stable concentration gradient of the attractant develops that causes directional migration of the cells. This view has been repeatedly challenged, and development of such gradients in vivo is unlikely. The present experiments were designed to test if a stable concentration gradient was required for normal dermal fibroblasts to migrate toward platelet derived growth factor. It was found that a brief pulse of the attractant was required and sufficient to induce chemotaxis. The pulse had to contain a specific concentration of attractant and was ineffective when not unilateral. The observed effects could not be attributed to induction of random migration or migration on a mediator-coated surface. It is not clear which machinery is regulating this cellular behaviour, but it is suggested that cells may migrate in vivo by similar mechanisms, because the establishment of stable concentration gradients of attractants in tissues is deemed unlikely. PMID- 2318906 TI - Amiloride inhibits constitutive internalization and increases the surface number of epidermal growth factor receptors in intact rat hepatocytes. AB - In previous experiments the surface expression of epidermal growth factor (EGF) receptors in freshly isolated rat hepatocytes varied temperature- and time dependently and was depleted by monensin and cycloheximide in a way suggesting that a subpopulation of these receptors are subject to constitutive cycling (Gladhaug and Christoffersen; 1988). We here report the finding that pretreatment of the hepatocytes with amiloride exerts marked effects on cellular EGF receptor movements. After 2 h incubation with 1 mM amiloride, the receptor level was approximately 270,000 sites/cell surface vs. 140,000 in the untreated cell, with no change in receptor affinity. Amiloride thus stabilized the surface EGF receptor pool at an elevated level. In cells pretreated with amiloride for 60 min, the relative endocytosis decreased from about 2.6 EGF molecules internalized per receptor during 15 min endocytosis in untreated cells to about 1.5 molecules/receptor in amiloride-treated cells. These results suggest that amiloride causes an accumulation of EGF receptors at the hepatocyte surface due to inhibition of constitutive receptor internalization. In addition, it was found that in amiloride-treated hepatocytes the phorbol ester TPA strongly inhibited high-affinity EGF binding without affecting the total surface receptor number. In control cells, TPA did not consistently affect binding. Pretreatment with amiloride prevented surface EGF receptor depletion induced by cycloheximide and puromycin, but it did not significantly inhibit surface receptor depletion caused by monensin. Although the underlying mechanism of the amiloride effect on intracellular receptor trafficking is not clear, the results provide further evidence for a continuous, ligand-independent EGF receptor cycling pathway in hepatocytes. PMID- 2318907 TI - Propagation of fetal human RPE cells: preservation of original culture morphology after serial passage. AB - The permissive effects of extracellular matrix (ECM) on in vitro growth and differentiation of fetal human retinal pigment epithelial (RPE) cells have been studied. Factors which enhanced the effect of ECM to support cell division were also examined, including growth factors, culture media, and serum requirement. Under the specific culture conditions we have defined, it is possible to propagate these RPE cells at low density (less than 20 cells/mm2) with excellent growth properties for greater than 72 doublings (fourteen passages) in serial culture. Later-passaged cells maintained the morphological appearance of early passaged cultures. ECM produced by bovine corneal endothelial cells was by far the most predominant factor in promoting rapid cell proliferation and viability over repeated passaging. Basic fibroblast growth factor (bFGF) exerted a substantial effect on the rate of cell division at different serum concentrations on plastic dishes. In addition, this factor showed profound synergistic effect when RPE cells were maintained on ECM, both in the preservation of cell morphology and also in long term viability. Other growth factors, such as epidermal growth factor (EGF) and transforming growth factor-beta (TGF-B), were also tested, but EGF effects were less prominent than those observed with bFGF, and TGF-B had an inhibitory effect at high concentrations. The ability to obtain a relatively large number of human RPE cells in vitro which preserve the appearance of early passage cells may provide useful opportunities to study the physiological properties and pathological alterations involving this important cell type. PMID- 2318908 TI - Contraction of vascular smooth muscle in cell culture. AB - The use of cultured vascular smooth muscle cells for the study of events related to excitation and contraction of smooth muscle has been limited by the inability to reliably induce contractile responses after subculturing of the cells. This limitation has been overcome by the cell culture preparation described herein. We demonstrate that appropriate responses to both smooth muscle agonists and vasodilators were preserved in cells that were serially subcultured. Fetal bovine pulmonary artery and aortic cell cultures were established following enzymatic dispersion of the medial portion of freshly harvested vessels. At various times after isolation, cells were transferred to microscope coverslips coated with a polymerized silicone preparation (polydimethyl siloxane). Tension forces generated by the cells were manifested as wrinkles and distortions of this flexible growth surface. Visual evidence of cell contraction in the form of increased wrinkling was documented for cells exposed to angiotensin II, carbachol, and KCl. Decreases in cell tension occurred following treatment with isoproterenol, and those relaxing effects were overcome by subsequent treatment with the agonist carbachol. The contractile responses did not diminish with prolonged maintenance in culture or repeated subculturing. Phosphorylation of the light chains on the contractile protein myosin was also measured as a biochemical index of agonist-induced contraction. Cells depolarized with KCl or exposed to carbachol showed increased myosin phosphorylation when analyzed by 2-dimensional gel electrophoresis. The responses remained intact through 7 passages and 9 weeks in culture. These results show that cultured vascular smooth muscle cells do not necessarily undergo a phenotypic modulation with loss of contractility under prolonged maintenance in culture. PMID- 2318909 TI - Modulation of Ca2(+)-dependent intercellular adhesion in bovine aortic and human umbilical vein endothelial cells by heparin-binding growth factors. AB - Cultured endothelial cells have been shown to possess two mechanisms of intercellular adhesion: Ca2(+)-dependent and Ca2(+)-independent. We report here that growth of bovine aortic endothelial cells (BAEC) in complete medium containing purified basic fibroblast growth factor (bFGF, 6 ng/ml) results in loss of Ca2(+)-dependent intercellular adhesion. In the presence of heparin (90 micrograms/ml), this effect is reproduced upon treatment with acidic fibroblast growth factor (aFGF, 6 ng/ml) or endothelial cell growth supplement (ECGS, 100 micrograms/ml), in both human umbilical vein endothelial cells (HUVEC) and BAEC. Treatment at these doses with aFGF in the absence of heparin or with heparin alone is without significant effect. Loss of Ca2(+)-dependent adhesion following treatment of cells with heparin-binding growth factors (HBGFs) is prevented by pre-treatment of cell layers with cycloheximide. The Ca2(+)-independent adhesion mechanism is unaffected by HBGF treatment. Exposure of endothelial cells to HBGFs, moreover, prevents the eventual establishment of quiescence in growing cultures and restimulates replication in confluent cultures that have reached a final density-inhibited state. Addition of bFGF alone or aFGF + heparin at these doses results in a 4-fold increase in DNA synthesis over untreated control cultures at saturation density as reflected by thymidine index. A single addition of bFGF (6 ng/ml) to untreated quiescent confluent BAEC monolayers results in an increase in 3H-TdR incorporation reaching a peak at 22 hours with a parallel loss of Ca2(+)-dependent adhesiveness. Fluorescent staining with rhodamine-phalloidin demonstrates an altered distribution of polymerized F-actin in the bFGF-treated monolayers, marked by disruption of the dense peripheral microfilament bands retained by untreated confluent monolayers. Together, these results indicate that the mitogenic effect of HBGFs in cultured endothelial cells is associated with a "morphogenic" set of responses, perhaps dependent on breakdown of calcium dependent cell-cell contacts. PMID- 2318911 TI - Transfer of a normal human chromosome 11 suppresses tumorigenicity of some but not all tumor cell lines. AB - The complete suppression of tumorigenicity of a human cervical cancer cell (HeLa) and a Wilms' tumor cell line (G401) following the introduction via microcell fusion of a single chromosome t(X;11) has been demonstrated by Stanbridge and co workers. To determine whether other tumor cell lines are suppressed by chromosome 11, we performed chromosome transfer experiments via microcell fusion into various human tumor cell lines, including a uterine cervical carcinoma (SiHa), a rhabdomyosarcoma (A204), a uterine endometrial carcinoma (HHUA), a renal cell carcinoma (YCR-1), and a rat ENU-induced nephroblastoma (ENU-T1). We first isolated a mouse A9 cell containing a single human chromosome 11 with integrated pSV2-neo plasmid DNA. Following microcell fusion of the neo-marked chromosome 11 with the various tumors mentioned above, we isolated clones that were resistant to G418 and performed karyotypic analyses and chromosomal in situ hybridization to ensure the transfer of the marked chromosome. Whereas the parental cells of each cell line were highly tumorigenic, SiHa and A204 microcell hybrid clones at early passages were nontumorigenic in nude mice and HHUA was moderately tumorigenic. On the other hand, YCR-1 and ENU-T1 microcell hybrid clones were still highly tumorigenic following the introduction of chromosome 11. Thus, the introduction of a normal chromosome 11 suppresses the tumorigenicity of some but not all tumors, suggesting that the function of the putative suppressor gene(s) on chromosome 11 is effective only in specific tumors. PMID- 2318910 TI - Reduction of DNA primase activity in aging but still proliferating cells. AB - The basis of the well-known decline in cell proliferation with increasing passage number of human diploid fibroblast-like cell cultures is not known. It has been found that DNA synthesis was deficient in the remaining but still proliferating cells, but when appropriate corrections reflecting the remaining dividing cells were made, the amount of DNA polymerase alpha bound to nuclear matrices was normal [Collins and Chu: Journal of Cellular Physiology 124:165-173, 1985]. In the present study, the declining percentages of S-phase and dividing cells were determined to provide better estimates of functional culture age than passage number. The amounts of DNA polymerase alpha and DNA primase activity were determined in cell lysates, permeabilized cells, and bound to nucleoids, which are residual nuclear structures similar to nuclear matrices except that no DNase digestion step is employed. As expected, IMR 90 DNA synthesis declined with age, even after corrections for the declining numbers of proliferating cells. DNA polymerase alpha and DNA primase activity in cell lysates, permeabilized cells, and bound to nucleoids declined with increasing age. However, after appropriate corrections for the declining fraction of proliferating cells, the only activity that declined was that of DNA primase bound to nucleoids. Thus, a decrease in the binding of DNA primase to the nuclear site of DNA synthesis may account for the decreased DNA synthesis in aging but still proliferating cells. PMID- 2318912 TI - Effect of information organization on recall of medication instructions. AB - This study compared immediate recall of prescription information when the message content was presented in a highly organized format versus a less-organized approach. Two groups of pharmacy students viewed separate videotapes, which described information for a patient about three fictitious medications. Students were then asked to recall the medications' name, colour, purpose, dosage, duration, side-effects and quantity prescribed. Students who viewed the organized version correctly recalled more information in every category except drug colour. Both groups made more errors in recalling dosage than any other category. Thus, organizing information facilitates recall of medication information. PMID- 2318913 TI - A pharmacokinetic study of high-dose metoclopramide suppositories. AB - The pharmacokinetics of high-dose rectal metoclopramide have been studied in nine patients after administration of 150-mg suppositories. The results have been compared to the pharmacokinetics of the drug in five patients who received the same dose of metoclopramide intravenously. Administration of a metoclopramide suppository achieved plasma drug concentrations that are associated with the effective treatment of cytotoxic drug-induced nausea and vomiting. In three patients who received the drug by both routes the systemic availability of the suppository appeared to be complete. High-dose metoclopramide suppositories are convenient and may be advantageous in the treatment of medical oncology out patients. PMID- 2318914 TI - Phenytoin dosage individualization--five methods compared in the elderly. AB - Five methods to predict phenytoin dosage have been compared in nine continuous care elderly patients. For each patient three steady-state plasma concentrations were obtained at three different doses. The data were used to estimate the 'optimum' dose for each patient by direct linear plot. The optimum dose for each patient was predicted from each plasma concentration using five dosage prediction methods based on the Michaelis-Menten equation using: (i) the population mean Vmax, (ii) the population mean KM, (iii) the linearized Bayesian method, (iv) the Rambeck nomogram, and (v) two plasma concentration-dose data pairs to estimate both Vmax and KM. The predictive precision was similar for each of methods (i iv). Ninety-six out of 126 dosage predictions with the five methods were within 25 mg of the optimum dose. Methods (ii) and (iv) tended to overpredict dosage, particularly when used to interpret low plasma phenytoin concentrations. PMID- 2318915 TI - A pharmacokinetic comparison of ibuprofen sustained-release tablets given to young and elderly patients. PMID- 2318916 TI - Stability of solutions of histamine acid phosphate after sterilization by heating in an autoclave. AB - Histamine acid phosphate (HAP) solutions are used in tests for asthma and also as positive controls in general allergenic testing. Previously these solutions have been sterilized, if at all, by filtration, thus limiting the shelf-life of the preparation and introducing some degree of uncertainty in their use. It is shown here that HAP solutions can be sterilized successfully by heating in an autoclave with little degradation and that subsequent storage of autoclaved solutions indicates a minimum shelf-life of 4 months. PMID- 2318917 TI - The management of a hospital formulary. AB - This paper describes the management of a hospital formulary that is operated by voluntary co-operation of prescribes. The organizational and philosophical factors associated with the formulary management system in a major teaching hospital environment are discussed. A combination of educative, re-educative, persuasive and facilitative strategies is used to influence prescribing behaviour. Both passive and active methods, including face-to-face intervention methods are practised. The formulary is reinforced with an extensive pharmacy monitoring operation which stimulates facilitative dialogue between pharmacists and prescribers and encourages medical self-audit and peer review. Evidence of compliance with recommended policies, and consequent control of drug expenditure are presented. PMID- 2318918 TI - Are there emotion perception deficits in young autistic children? AB - Two studies were conducted to test the hypothesis that young autistic children are selectively impaired on emotion perception tasks. Results supporting the hypothesis were found on two of the four measures when the controls used were matched on non-verbal mental age; performance on the other tasks was consistent with global deficits across affective and non-affective domains, rather than specific deficits in emotion perception. When the autistic group was compared with controls matched on verbal mental age, no group differences were found. These results suggest that emotion perception impairment is not likely to be the primary underlying deficit in autism. Additional areas for further investigation were suggested. PMID- 2318919 TI - Childhood obsessive-compulsive disorder: a prospective follow-up study. AB - Twenty-five of 27 patients (93%) who had participated in a study of severe primary obsessive-compulsive disorder with onset in childhood or adolescence, were seen 2-7 yrs after initial examination (mean, 4.4 yrs). They were compared to a group of normal controls matched for age, sex and IQ and followed up for the same period. Continued psychopathology was striking for the patients, with only seven (28%), three males and four females, receiving no psychiatric diagnosis at follow-up. Seventeen subjects (68%) still had obsessive-compulsive disorder, 12 patients (48%) had another psychiatric disorder, most commonly anxiety and/or depression; neither initial response to clomipramine or any other baseline variable predicted outcome. PMID- 2318920 TI - Hyperactivity and parental psychopathology. AB - The association of child hyperactivity and parental psychopathology was explored by establishing lifetime DSM-III diagnoses and histories of childhood hyperactivity among the parents of boys, aged 7-11 yrs, in five diagnostic groups: attention deficit disorder with hyperactivity (ADDH), conduct disorder (CD), ADDH + CD, emotional disorder (ED) and no disorder (NC). These groups were differentiated by a family history of parental psychopathology or childhood hyperactivity. ADDH + CD, CD and ED groups all had significantly higher rates of parental psychopathology than the ADDH and NC groups, for which rates were similar. Significantly more boys in the ADDH, CD and ADDH + CD groups had family histories of parental childhood hyperactivity than did boys in the ED and NC groups. PMID- 2318921 TI - Behaviour and personality in childhood as predictors of adult psychiatric disorder. AB - Associations between childhood behaviour and personality and adult affective disorder were investigated in a 36-year follow-up of a national birth cohort. A number of early characteristics were significantly related to adult outcome including enuresis, nailbiting, speech problems, truancy and composite indices of behaviour and personality. Continuity was not explained by factors acting independently on child and adult measures. Prediction of adult disorder, although better for women, was modest in both sexes and sensitivity and specificity would not justify widespread intervention. However, childhood measures should prove valuable in investigating chains of influence on adult disorder, occurring throughout individuals' life histories. PMID- 2318922 TI - Premature termination from treatment among children referred for antisocial behavior. AB - The present study examined differences between children and families who complete treatment versus those who terminated prematurely. Children (N = 81, ages 7-13 years) referred to outpatient treatment for severe antisocial behavior and their families participated. It was predicted that families who terminate treatment prematurely would show greater dysfunction in four domains: child severity and breadth of antisocial behavior, maternal stress, maternal psychopathology, and socioeconomic disadvantage. The results indicated that among cases who terminate treatment prematurely children evinced more severe conduct disorder symptoms and more delinquent behaviors; mothers reported greater stress from their relations with the child, their own role functioning, and life events; and families were at greater socioeconomic disadvantage than those who remained in treatment. The implications of the present findings for the design and implementation of treatment of antisocial children and their families are discussed. PMID- 2318923 TI - Parent-child agreement on symptoms assessed via a clinical research interview for children: the Child Assessment Schedule (CAS). AB - This study examined the relationship between symptom type and parent-child agreement, as reflected in symptom scores on a structured diagnostic interview, the Child Assessment Schedule (CAS). Forty-eight psychiatric inpatients (mean age 10 years) were administered the CAS. Their mothers were interviewed independently with the parent form. The average time between interviews was 12 days. High parent-child agreement was found for conduct/behavioral problems and moderate agreement for affective symptoms. Parents reported more conduct-related problems; children reported more anxiety and somatic symptoms and more family problems. The pattern of parent-child differences was the same as observed for other interviews. PMID- 2318924 TI - Sex differences in the hyperkinetic syndrome of childhood. AB - Among a clinic sample of 6525 subjects, 61 males and 18 females with an ICD-9 diagnosis of the hyperkinetic syndrome of childhood were identified. Hyperactive girls had a lower IQ and significantly higher rates of language disorders and neurological disorders, suggesting a possible neurological basis for hyperactivity in females. In contrast, there was a population of male hyperactives with less evidence of brain dysfunction and a normal IQ, evidence compatible with the model of greater male constitutional variability. There was little evidence for the polygenetic multiple threshold model of sex inheritance. PMID- 2318925 TI - The child's construing of nocturnal enuresis: a method of inquiry and prediction of outcome. AB - Fifty-five children with nocturnal enuresis were engaged in a structured interview prior to treatment with the body-worn alarm. The interview sought to understand how children make sense of the experience and examines the implications for becoming dry. Successful treatment outcome was found to be associated with the child both construing bedwetting psychologically, and indicating no resistance to change. The importance of establishing the child's attitude to bedwetting prior to treatment is stressed. PMID- 2318926 TI - Validation of hyperactive, aggressive, and mixed hyperactive/aggressive childhood disorders: a research note. AB - Eighty-five non-referred school children were divided into four groups based upon the IOWA Conners Teacher's Questionnaire: pure hyperactive (HYP), pure aggressive (AGG), mixed hyperactive/aggressive (HYP/AGG), and normal controls. The groups were compared on neurobehavioral tests believed to assess inattention and impulsivity. A continuous performance test indicated that the HYP group was more inattentive than the other groups and the HYP/AGG group was most impulsive. The AGG group did not differ from controls. The data support the distinction between HYP, AGG and HYP/AGG groups of children selected by the IOWA Conners. PMID- 2318927 TI - Self-esteem as determined by gender differences among Yoruba adolescents in Ibadan, Nigeria: a research note. AB - This study investigates the influence of gender differences on the expression of self-esteem among Yoruba adolescents. Using a sample of 120 adolescents, 60 males and 60 females, with a mean age of 16.02 years (S.D. = 1.63), the results reveal that male adolescents express higher self-esteem than female adolescents. This finding is attributed to the differing socialization processes for males and females in Yoruba societies. PMID- 2318928 TI - Toward a more precise understanding of mental retardation. PMID- 2318929 TI - A new method for extracting DNA or RNA for polymerase chain reaction. AB - The use of glass powder suspension for the extraction of RNA or DNA was studied to simplify the procedures of polymerase chain reaction (PCR). Using this procedure, proviral DNA of human T-lymphotropic virus type-1 (HTLV-1) in the blood of an asymptomatic virus carrier and viral RNA of human immunodeficiency virus (HIV) in the blood of an AIDS patient were easily detected by PCR employing glass powder. The use of glass powder is a simple and highly efficient procedure for the extraction of DNA or RNA, and can be applied for routine PCR. PMID- 2318930 TI - Development of automated immunoassays for immune status screening and serodiagnosis of rubella virus infection. AB - The fully automated IMx immunoassay analyzer was used to develop a system for the detection of IgG and IgM antibodies to rubella virus for immune status screening and diagnosis of primary infections. Reagents and assay protocol software were developed using rubella virus sensitized microparticles as the solid phase to capture specific antibodies from serum samples. Anti-human IgG or IgM antibody coupled to alkaline phosphatase enzyme followed by methylumbelliferyl phosphate substrate was used to detect the presence or absence of antibodies specific to the antigens on the solid phase. To evaluate the efficacy of the IMx rubella IgG assay, immune status screening was performed with a clinical patient population of 501 sera. When compared to an IgG specific enzyme immunoassay and passive hemagglutination assay the agreement was greater than 99%. The IMx rubella IgM assay was utilized to determine the presence of rubella specific IgM antibodies in 462 sera. These results were compared to IgM specific enzyme immunoassay results and also demonstrated greater than 99% agreement. Seroconversion following rubella vaccination of susceptible individuals was demonstrated by IgG and IgM antibody responses as early as two weeks postvaccination. In addition to automation, the IMx system offers rapid assay times and calibration curve storage without sacrificing clinical efficacy. PMID- 2318931 TI - Effects of L-thyroxine and iodide on the development of autoimmune postpartum thyroiditis. AB - In the present study we examined the influence of L-T4 and iodide on autoimmune postpartum thyroiditis. Women at risk of developing the disease were identified in early pregnancy by the presence of moderate or high titers of antibodies against thyroid peroxidase (TPOAb). They were given no treatment (n = 20), 0.1 mg L-T4 daily (n = 18), or 0.15 mg iodide daily (n = 20) for 40 weeks postpartum. Changes in thyroid function were seen in all women, although in nine hormone values remained within the reference ranges of erthymoid individuals. In each group of women, thyrotoxicosis occurred around 2-3 months postpartum, followed by a gradual rise of TPOAb. Subsequently, around 5-7 months postpartum, a hypothyroid phase was observed. TSH elevations (greater than 5 mU/L) occurred in 9 of 18 women in spite of treatment with 0.1 mg L-T4 although elevations were lower than in the other two groups. Among those women who developed abnormal thyroid function, the hormone changes appeared greater in the iodide-treated group than in the control group, suggesting that in certain patients iodide may aggravate rather than ameliorate the disease. All 58 women showed a reduction of TPOAb during pregnancy and a transient rise during the postpartum year. The extent of TPOAb elevations did not differ between the groups. Thus, the administration of L-T4 prevented hypothyroid symptoms, but did not alter the course of the postpartum thyroiditis, which appears not to be accelerated by events of target cell origin. PMID- 2318933 TI - Bile acids in human breast cyst fluid: the identification of lithocholic acid. AB - Breast cyst fluid (BCF) aspirated from 12 women with fibrocystic disease of the breast and sera obtained simultaneously were analyzed for bile acids. Analysis was performed by gas-liquid chromatography of the acetoxy methyl esters of the bile acids prepared after alkaline hydrolysis of the bile salts. An internal standard served to correct for methodological losses. Low levels of bile acids were found in serum samples, precluding overt hepatobiliary complications. Deoxycholic acid (17-160 mumol/L), chenodeoxycholic acid (18-305 mumol/L), and cholic acid (3-119 mumol/L) were detected in 11 of 12 samples of BCF. In 2 cases, chosen at random, the identities of the bile acids were verified by mass spectrometry. Lithocholic acid (9-23 mumol/L), a reported cocarcinogen, was detected in 6 of the 12 samples of BCF. This is the first report of the presence of lithocholic acid in BCF with confirmation by Mass spectrometry. There was no correlation between the levels of individual bile acids and those of potassium ion, Na+/K+, estriol-3-sulfate, or 16 alpha-hydroxyandrogen sulfates that had been quantified previously in these samples. There was borderline correlation between concentrations of total bile acids and K+ (P less than 0.06) and Na+/K+ (P less than 0.07). Yet to be elucidated are the mechanism of accumulation of bile acids in BCF and whether levels of particular bile acids in BCF may serve to identify that small subset of women with fibrocystic disease at risk for developing breast cancer. PMID- 2318934 TI - Ketoconazole decreases the serum 1,25-dihydroxyvitamin D and calcium concentration in sarcoidosis-associated hypercalcemia. AB - Ketoconazole is an antifungal agent capable of inhibiting human steroid hormone synthesis, including renal 1,25-dihydroxyvitamin D [1,25-(OH)2D] synthesis. The ability of this drug to inhibit the extrarenal production of 1,25-(OH)2D, as occurs in human granuloma-forming disease states, including sarcoidosis, has not been evaluated. We examined the effect of ketoconazole on the 1,25-(OH)2D-calcium homeostatic mechanism in a hypercalcemic patient with sarcoidosis and on the synthesis of 1,25-(OH)2D3 in vitro by cultured pulmonary alveolar macrophages (PAM) from this and another host. Oral ketoconazole therapy (800 mg/day) decreased the serum 1,25-(OH)2D concentration 73% within 4 days; this was associated with a 15% decrease in the serum calcium concentration and a 57% decrease in the fractional urinary calcium excretion rate. In vitro, ketoconazole had a rapid onset, concentration-dependent inhibitory effect on sarcoid PAM 1,25 (OH)2D3 synthesis (ED50 = 0.1 mumol/L) that was not reversible by exposure to leukotriene C4, a potent stimulator of PAM 1,25-(OH)2D3 synthesis. Kinetic analysis of ketoconazole's action on the macrophage 1 alpha-hydroxylation reaction was examined at concentrations achieved in vivo when the drug is given orally. The velocity of the 1 alpha-hydroxylation reaction at ketoconazole concentrations of 0.01-1.0 mumol/L increased as the concentration of substrate 25 hydroxyvitamin D3 increased from 12-2000 nmol/L. PMID- 2318932 TI - Measurement of inhibin concentrations in men: study of changes after castration and comparison with androgen levels in testicular tissue, spermatic venous blood, and peripheral venous blood. AB - We measured serum inhibin levels in eight untreated patients with prostatic cancer undergoing castration by RIA using an antiserum against 31-kDa bovine follicular fluid inhibin. The inhibin concentrations in testicular tissue and spermatic venous blood were also measured in six of these patients. Serum inhibin levels (mean +/- SD, 377.8 +/- 212.1 U/L), declined rapidly after castration (15 min after, 233 +/- 171.4; 30 min, 224.6 +/- 156.6; 1 h, 181.5 +/- 95.9; 2 h, 174.3 +/- 69.4; 4 h, 122 +/- 6.4; 6 h, less than 120). High concentrations of inhibin were detected in testicular tissue (31,360 +/- 15,180 U/kg), and the levels in spermatic venous blood (3,178.3 +/- 1,386.8 U/L) were approximately 10 times greater than those in peripheral blood (385.5 +/- 233.1 U/L). Testosterone levels were 1,968.2 +/- 992.3 nmol/kg in testicular tissue and approximately 100 times greater in spermatic venous blood (1,631.6 +/- 389.7 nmol/L) than in peripheral blood (18.0 +/- 4.4 nmol/L). These results suggest that circulating inhibin in men mainly originates from testis and that one of the routes of secretion is via the bloodstream. PMID- 2318935 TI - The effects of the menopause on calcitriol and parathyroid hormone: responses to a low dietary calcium stress test. AB - Calcium, calcitriol and PTH levels were studied in 11 premenopausal women, aged 41 +/- 3 yr (mean +/- SD), and 11 postmenopausal women, aged 42 +/- 3 yr, at baseline and in 9 women from each group during a 4-day low calcium diet. Serum dialyzable calcium and urinary hydroxyproline excretion were higher in the postmenopausal women at baseline and throughout the low calcium diet. Baseline calcitriol levels were significantly lower in the postmenopausal women, but these were associated with lower vitamin D-binding protein levels; the calculated free calcitriol index was not different between the two groups. After the low calcium diet calcitriol levels rose in both groups to similar levels. PTH levels were not different in the two groups at baseline and rose to the same level on the low calcium diet. These data indicate that estrogen deficiency at the menopause is not associated with deficient calcitriol or PTH reserve, although basal calcitriol levels may be reduced secondarily due to lower vitamin D-binding protein levels or relative hypercalcaemia. PMID- 2318936 TI - Effects of tamoxifen treatment on plasma lipids and lipoprotein lipid composition. AB - Concern has been raised that long term treatment with the antiestrogen tamoxifen might predispose women to the rapid development of cardiovascular disease. Since estrogen-induced changes in plasma lipids confer protection to females from coronary heart disease, we have examined the impact of tamoxifen on lipoprotein levels and composition on eight posmenopausal women. After 3 months of tamoxifen treatment (10 mg, twice daily), no significant changes were observed in either whole plasma triglyceride (pre-Rx, 137 +/- 59; post-Rx, 157 +/- 110 mg/dL) or cholesterol (pre-Rx, 193 +/- 23; post-Rx, 204 +/- 14 mg/dL); plasma free (unesterified) cholesterol (FC), however, fell significantly (pre-Rx, 66.5 +/- 6.5; post-Rx, 59.6 +/- 4.6 mg/dL; P less than 0.05). Since plasma lecithin (L) was unchanged, the FC/L ratio declined significantly to levels observed in healthy menstruating women (pre-Rx, 95 +/- 0.16; post-Rx, 0.74 +/- 0.12 molar ratio; P less than 0.025). In low density lipoprotein (LDL), the concentrations of cholesterol and FC and the FC/L ratio all fell significantly (P less than 0.025, P less than 0.05, and P less than 0.025, respectively). Despite a tendency for high density lipoprotein2 cholesterol (HDL2-C) to increase (pre-Rx, 9.7 +/- 3.6; post-Rx, and 14.4 +/- 13.3 mg/dL; P less than 0.4) and phosphoinositol to fall, there were few clear-cut alterations in either HDL2 or HDL3 surface or core lipid composition. The combination of reduced HDL3 lysolecithin (P less than 0.025) associated with a posttreatment trend toward increased triglyceride/cholesterol esters ratios in both HDL subfractions are findings consistent with tamoxifen-induced inhibition of hepatic lipase. These changes in lipoprotein composition together with the fall in LDL cholesterol and increase in sex hormone-binding globulin (P less than 0.005) indicate that tamoxifen acts as an estrogen agonist on the liver. Since elevated LDL cholesterol levels and qualitatively altered lipoproteins enriched in FC are both associated with increased coronary risk, the improvement noted in these parameters after tamoxifen should allay to some degree anxiety about its use with regard to cardiovascular risk. PMID- 2318937 TI - The amino acid sequence of the insulin receptor is normal in an insulin-resistant Pima Indian. AB - Insulin resistance is an early predictor of development of noninsulin-dependent diabetes mellitus (NIDDM) in Pima Indians, a population with the highest reported prevalence of NIDDM. The insulin receptor plays a central role in mediating insulin action, and previous studies have demonstrated that mutations in the insulin receptor gene may cause insulin resistance. Therefore, we have cloned the insulin receptor cDNA from an insulin-resistant Pima Indian to determine if there is a mutation in the patient's insulin receptor gene. We obtained nine cDNA clones spanning exons 4-10 and 12-22 of the patient's insulin receptor gene. Polymorphisms in the nucleotide sequences for codons 523 (Ala), 1058 (His), and 1062 (Leu) provided useful markers to differentiate the patient's two alleles of the insulin receptor gene. These substitutions were silent, in that they did not alter the predicted amino acid sequence. The sequence of exons 1-3 and 11 was determined directly from genomic DNA that had been amplified using the polymerase chain reaction catalyzed by Taq DNA polymerase. Other investigators have reported defects in insulin binding and insulin receptor tyrosine kinase activity in diabetic Pima Indians. However, we did not detect any mutations in this patient's insulin receptor gene. Thus, these observations are consistent with the interpretation that the defects in insulin receptor function are acquired rather than derived from defects in the primary structure of the receptor. PMID- 2318938 TI - Short-term effects of growth hormone on fuel oxidation and regional substrate metabolism in normal man. AB - Primarily by increasing the availability of lipid intermediates, GH is likely to have profound effects on substrate consumption rates. To examine the short term actions of GH on glucose turnover, fuel oxidation and regional forearm metabolism, six normal volunteers were each studied twice for 5.5 h after having received a 4-h infusion of GH (20 ng/kg.min) or saline. GH induced slightly falling plasma glucose levels, acute 40-50% decreases in forearm glucose uptake, and no change in glucose turnover. Furthermore, substantial increases in circulating concentrations and forearm uptake of nonesterified fatty acids and 3 hydroxybutyrate were recorded. Although GH infusion was followed by a 50% reduction of forearm alanine release hepatic nitrogen excretion seemed unaffected. Energy expenditure was not influenced by GH, but the non-protein respiratory exchange ratio decreased from a basal value of 0.778 +/- 0.008 to 0.732 +/- 0.007 after GH treatment (P less than 0.05). Correspondingly, lipid oxidation increased from 1.20 +/- 0.06 to 1.48 +/- 0.09 mg/kg.min, and glucose oxidation decreased from 0.97 +/- 0.12 to 0.39 +/- 0.06 mg/kg.min (P less than 0.05). Nonoxidative glucose utilization tended to increase. These data indicate that GH, by promoting lipid utilization and decreasing glucose oxidation, diminishes the need for gluconeogenesis and, therefore, could be protein preserving in the long term. Overall, we found no evidence of GH having acute insulin-like effects on glucose metabolism. GH appears to increase glucose storage, leaving total energy expenditure unaffected. PMID- 2318939 TI - Purified first and third trimester placental trophoblasts differ in in vitro hormone secretion. AB - In vitro studies with cytotrophoblasts obtained from term placentas have shown low levels of placental protein hormone secretion during the first 2 days in culture, followed by a marked increase during days 3 and 4. Since maternal serum placental hormone levels at term and during the first trimester differ, it is conceivable that cytotrophoblasts from first trimester placentas will differ in endocrine function from those derived from term placentas. Therefore, we examined the secretion of hCG, hCG alpha, human placental lactogen (hPL), and progesterone (P) both in the basal state and after exposure to 8-bromo-cAMP or endogenous cAMP stimulation with cholera toxin in cytotrophoblasts purified by enzymatic dispersion and Percoll gradient centrifugation from four first trimester and four third trimester placentas. At the time of seeding, all cells were mononuclear, and the degrees of aggregation and syncytia formation were similar in first and third trimester trophoblasts during the 4 days in culture. First trimester trophoblasts secreted greater quantities of hCG than did term trophoblasts, while basal secretion of hCG alpha, hPL, and progesterone were similar. Qualitative differences in the hormone secretory patterns were apparent. hCG secretion by first trimester trophoblasts decreased over the 4 days in culture, while the amounts secreted by third trimester trophoblasts increased. hCG alpha levels increased for 2-3 days in first trimester trophoblasts and then decreased, while hCG alpha increased in term trophoblast medium over the 4 days. The ratio of hCG alpha to hCG in media from first and third trimester cultures reflected the relative ratios of these hormones in placental tissue and maternal serum at analogous stages of pregnancy. hPL concentrations in the medium declined between days 3-4 in first trimester cultures, while they increased between days 3-4 in third trimester cultures. The secretory pattern of P was somewhat more erratic. cAMP stimulation led to a similar rise in hCG, hCG alpha, and P secretion in first and third trimester trophoblasts, and a variable response for hPL secretion. These results indicate that the functional activity of placental trophoblasts in culture depends in part upon the age of the placenta from which the cells are derived. The differences may represent intrinsic differences in function or the presence of inhibitory or stimulatory factors of maternal, fetal, or trophoblast origin. PMID- 2318940 TI - The impact of osteophytic and vascular calcifications on vertebral mineral density measurements in men. AB - To evaluate the influence of extravertebral calcification on spinal bone density determinations, we measured lumbar vertebral density in 71 hospitalized and 58 normal men using dual photon absorptiometry. The extent of vascular and osteophytic calcification was graded from lateral lumbar radiographs. Fifty-five (43%) of the subjects had identifiable osteophytes, and 86 (67%) had vascular calcifications. Despite similar ages and weights in subjects with and without ostephytes, those with osteophytes had greater spinal density (1.34 vs. 1.17 g/cm2; P less than 0.001), and there was a strong correlation between osteophyte severity and spinal density (r = 0.41; P less than 0.00001). Proximal femoral density was not different in those with and without osteophytes. The distribution of osteophytes in this population was not random, and as a result, the presence of osteophytes obscured the the relationship of bone density to age as well as the comparison of hospitalized to normal men. Vascular calcification had a minimal effect on vertebral density. In summary, osteophytic calcification exerted an important influence on the measurement of spinal bone density in men. This effect should be considered in both clinical and research applications of integral vertebral density measures. PMID- 2318941 TI - Immunoreactive inhibin alpha-subunit in human serum: implications for radioimmunoassay. AB - The specificity of the most widely used heterologous RIA for human serum inhibition was examined with regard to its cross-reactivity with the alpha subunit of inhibin. Using a mixture of recombinant alpha inhibin proteins, including precursor and mature forms, the epitopic specificity of this antibody was localized entirely to the alpha-subunit. Furthermore, varying degrees of alpha inhibin immunoactivity were demonstrated in serum from normal subjects and patients with various reproductive disorders by both Western blot and RIA. These results demonstrate that data obtained using this RIA should be interpreted with caution as to the degree to which they reflect the presence of intact dimeric inhibin vs. alpha inhibin proteins in the circulation. PMID- 2318943 TI - Clinical review: Diagnosis and management of abnormal plasma lipids. PMID- 2318942 TI - The effect of intraluteal infusion of deglycosylated human chorionic gonadotropin on the corpus luteum in rhesus monkeys. AB - Removal of the carbohydrates from hCG results in an antagonist (degly-hCG) that competitively inhibits hCG/LH-stimulated adenylate cyclase in macaque luteal tissue in vitro, but its effect in vivo is controversial. To examine the effect of degly-hCG on the lifespan and steroidogenic activity of the primate corpus luteum, the antagonist was administered to female rhesus monkeys (n = 7) beginning at the midluteal phase of the menstrual cycle. In a control cycle the saline vehicle was infused via an osmotic minipump directly into the corpus luteum. In a subsequent cycle, one of three dose rates of degly-hCG (0.001, 0.009, and 0.09 nmol/h) was infused into the corpus luteum. Pump implantation and infusion began 5-9 days after the midcycle LH surge and continued for 7 days. Peripheral venous blood was collected daily from day 8 of the cycle until menses, and serum progesterone levels were determined by RIA. Progesterone levels and patterns were similar in animals that received either the saline vehicle or degly hCG, and the length of the luteal phase in monkeys receiving any dose of degly hCG (16.4 +/- 0.5 days) was not different from that in animals receiving a control infusion (16.1 +/- 0.9 days). In a corollary study, an intraluteal infusion of degly-hCG (0.009 nmol/h) in the midluteal phase did not prevent stimulation of progesterone levels after im injection of hCG (15 IU/day for 5 days). We conclude that whereas degly-hCG is a useful tool to examine gonadotropin action in vitro, it is not a potent gonadotropin antagonist in vivo. PMID- 2318944 TI - Comments about the need for prenatal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. PMID- 2318945 TI - Blindness impairs plasma growth hormone response to L-dopa but not to arginine. AB - To investigate how blindness influences GH secretion, we studied the GH response to L-dopa and arginine in 8 blind adult males and 10 normal age-matched control males. Arginine and L-dopa tests were performed in random order at least 1 week apart at 0800 h, and plasma GH was measured by RIA. The blind subjects showed GH responses to arginine similar to those in normal subjects [peak, 22.1 +/- 1.3 vs. 20.5 +/- 1.3 micrograms/L (+/- SE)], but their GH response to L-dopa was significantly reduced [peak, 5.4 +/- 1.3 vs. 20.3 +/- 2.4 micrograms/L (+/- SE); P less than 0.01]. Because L-dopa is believed to release GH by stimulating endogenous GHRH, whereas arginine may act by suppressing endogenous somatostatin secretion, we propose that blindness may impair GH release by inhibiting GHRH secretion. PMID- 2318946 TI - Body fat mass, body fat distribution, and plasma hormones in early puberty in females. AB - We examined whether there is a relationship between body fat mass or body fat distribution and hormonal profiles in the plasma of early pubertal girls. Thirty five apparently healthy caucasian schoolgirls were selected for Tanner's breast development stage M2; they had all been classified as being stage M1 6 months earlier. Body fat mass had no relationship with the total plasma sex steroid concentration or gonadotropins. However, body fat mass was correlated with the fraction of testosterone that was not bound to sex hormone-binding globulin and considered the fraction available for biological activity. Body fat distribution, rather than body fat mass, was different in relation to the total concentrations of estrone, estradiol (E2), and testosterone as well as the percentage of available E2 or testosterone. Girls with fat localized predominantly on the hips had the highest levels of sex steroids and gonadotropins. It seems likely that this type of fat distribution is a result of ovarian activity. Girls with predominantly abdominal fat were also more obese and showed increased plasma levels of total E2 and a lower androgen/estrogen ratio in plasma, possibly due to increased aromatization, especially in abdominal adipose tissue. The findings suggest a reciprocal relationship among body fat distribution, plasma sex hormone levels, and availability of sex steroids in early female puberty. PMID- 2318947 TI - Androstenedione and estrone dynamics in hypothyroid women. AB - To examine the effects of hypothyroidism on androstenedione (A) and estrone (E1) metabolism, we infused eight women with [3H]androstenedione and [14C]estrone when they were hypothyroid and again when they were euthyroid after levo-T4 administration. MCRs and conversion ratios were measured using concentrations of radioactivity in the blood pools of A and E1. Peripheral aromatization was measured from the concentrations of radioactivity in the E1 glucuronide pool in the urine. After the women were euthyroid, the MCR of A had increased in seven of eight, the MCR of E1 increased in all eight, and peripheral aromatization had decreased in seven of eight. These findings indicate that hypothyroidism results in a decrease in the MCRs of A and E1 and, in most subjects, an increase in peripheral aromatization of A to E1. PMID- 2318948 TI - The histomorphometry of bone in primary hyperparathyroidism: preservation of cancellous bone structure. AB - To evaluate the effects of primary hyperparathyroidism (PHPT) on bone mass and structure, we have studied the iliac crest biopsies of 27 patients, 10 males (28 68 yr old) and 17 females (26-72 yr old) with mild PHPT after in vivo tetracycline labeling. All patients had mild hypercalcemia in the absence of any other cause and elevated levels of PTH without radiological evidence of bone disease. Static parameters of bone turnover (osteoid surface, osteoid volume, and eroded surface) were elevated in both men and women compared to normal values; the midmolecule RIA for PTH (PTHMM) was positively correlated with osteoid surface (r = 0.44; P less than 0.025) and eroded surface (r = 0.58; P less than 0.005). Dynamic parameters of bone turnover (mineralizing surface, expressed as double plus half single labeled surface, and bone formation rate at tissue level) were elevated compared to normal values; PTHMM was positively correlated with double plus half single labeled surfaces (r = 0.33; P less than 0.05) and with bone formation rate at the tissue level (r = 0.37; P less than 0.05). The mineral apposition rate was within the limits of normal values and positively correlated with PTHMM (r = 0.34; P less than 0.05). Histomorphometric parameters of bone structure [cancellous bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), cortical thickness (Ct.Th), and total bone density (TBD)] were compared to those in 20 autopsy control subjects, 12 men (33-60 yr old) and 8 women (27-75 yr old). BV/TV and Tb.N were significantly higher in PHPT patients than controls (P less than 0.02 and P less than 0.001, respectively). Tb.Sp was significantly lower in PHPT patients than controls (P less than 0.001), whereas Tb.Th was not significantly different between PHPT patients and controls. Ct.Th was significantly lower in PHPT patients than in controls (P less than 0.001), whereas TBD was not significantly different between the two groups. BV/TV was negatively correlated with age in both controls and PHPT patients. Tb.N showed a negative correlation and Tb.Sp a positive correlation with age in controls (r = -0.47; P less than 0.05 and r = 0.52; P less than 0.02, respectively), but they were not significantly dependent on age in PHPT patients. Tb.Th, while showing no significant age-related change in controls, was negatively correlated with age in PHPT patients (r = -0.42; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2318949 TI - Somatropin and wound healing after injury. AB - The anabolic effect of biosynthetic human GH (somatropin) has been assessed in both unburned and burned rats. Eighty rats, which had undergone standardized laparotomies, were randomly allocated to four groups (control placebo, control somatropin, burn placebo, and burn somatropin). Healing of the laparotomy wounds was assessed tensiometrically on the 6th and 14th postoperative days. Burned rats lost weight significantly and had significantly lower hemoglobin and serum albumin concentrations than control rats on both the 6th and 14th days. The peak forces applied to their musculo-fascial and skin wounds were significantly decreased on the 6th day only. The control somatropin group had significantly stronger musculo-fascial wounds than the control placebo group on the 6th day. Somatropin administration had no effect on burned rats. It is concluded that the limited anabolic activity of somatropin in rats with normal pituitary function is abolished by injury. PMID- 2318950 TI - Suppression of parathyroid hormone secretion with oral calcium in normal subjects and patients with primary hyperparathyroidism. AB - Exquisite sensitivity of normal parathyroid glands to small changes in ambient calcium concentrations and impaired sensitivity in primary hyperparathyroidism have been shown in vitro. Using an assay for PTH that detects rapid changes in PTH secretion (N-terminal-specific RIA; normal range, less than 3-33 pg/mL), we determined PTH suppressibility in response to a standardized dose of oral calcium in normal subjects and patients with primary hyperparathyroidism. Nine normal subjects were given oral calcium (25 mg/kg), and blood was analyzed half-hourly for 3 h for calcium and N-terminal PTH (N-PTH). Serum calcium rose by 0.34 +/- 0.06 mg/dL (0.085 +/- 0.015 mmol/L), and N-PTH levels declined rapidly from 15.3 +/- 1.4 to 4.2 +/- 1.1 pg/mL (-73 +/- 6%; P less than 0.01). In six subjects N PTH concentrations became undetectable. Nine patients with primary hyperparathyroidism were tested in the same manner. Serum calcium rose by 0.53 +/ 0.1 mg/dL (0.13 +/- 0.025 mmol/L), and N-PTH levels declined less, from 66 +/- 14 to 52 +/- 12 pg/mL (-21 +/- 4%; P less than 0.05). In none of the patients was the PTH reduced to less than 20 pg/mL. These results illustrate in vivo that the PTH response to oral calcium in primary hyperparathyroidism is markedly different from that in normal subjects. PMID- 2318951 TI - Changes in the pharmacokinetics of plasma total and free prednisolone during daily and intermittent regimens. AB - To determine the pharmacokinetic changes of prednisolone associated with differing therapy regimens, we studied 15 patients with various diseases who were treated with daily doses of prednisolone and were then placed on an intermittent regimen, [administration for 4 consecutive days (on-day period), followed by 3 days cessation (off-day period)]. The mean duration of the study and the mean total dosage were 1.6 months and 2.4 g in the daily period, respectively, and 4.7 months and 3.5 g in the intermittent period, respectively. Blood was drawn for 6 h after iv administration of 20 mg prednisolone (average, 0.36 mg/kg). Plasma total and free prednisolone concentrations were measured by RIA. On-day and off day tests were performed during the same week. The mean MCR of both total and free prednisolone decreased significantly in the daily and on-day periods compared with the pretreatment values. The decreased MCR during the on-day period was restored to the pretreatment level during the off-day period. A similar trend was observed in the changes in half-life, prolongation in the daily and on-day periods compared with the pretreatment value, and restoration to the pretreatment level during the off-day period. These alterations were not associated with the total duration or the total dosage of prednisolone administered. The results indicate that the pharmacokinetic parameters of prednisolone may periodically change during the intermittent regimen, and that off-day and on-day parameters are similar to those before therapy and during the daily period, respectively. PMID- 2318952 TI - Changes in serum triiodothyronine (T3) kinetics after prolonged Antarctic residence: the polar T3 syndrome. AB - Humans who live in Antarctica for greater than 5 continuous months demonstrate alterations in the hypothalamic-pituitary-thyroid axis. These changes are characterized by 1) increased pituitary release of TSH in response to iv TRH, 2) increased serum clearance of orally administered T3, and 3) normal serum total, free T4, and unstimulated TSH levels. To clarify the mechanism responsible for these findings, serum kinetic studies of 125I-labeled T4 and T3 were carried out in a group of normal men, first in California, then after 20 and 42 weeks of continuous Antarctic residence. The kinetic parameters were calculated by noncompartmental analysis. The mean T4 residence time (MRT) was not different before and after 42 weeks (5.54 +/- 0.50 and 5.08 +/- 0.43 days). The total T4 volume of distribution (TVd) tended to fall over the same period (4.30 +/- 0.12, 3.56 +/- 0.27 L/m2), but was not significantly different (P = 0.075). In contrast to T4, there was an increase from control values for the T3 MRT from 0.83 +/- 0.03 to 1.10 +/- 0.03 days (P less than 0.002) and a more than doubling of the T3 TVd from 15.55 +/- 0.52 to 47.24 +/- 5.09 L/m2 (P less than 0.002) after 42 wk of Antarctic residence. Energy intake increased approximately 40% throughout the study without a change in body weight. The changes in T3 kinetic parameters may be accounted for by increased extravascular tissue binding. The marked increase in T3 TVd and the small increase in MRT are associated with increased T3 production and clearance and only minor changes in T4 kinetics. This is the first description of a mechanism for the change in thyroid hormone economy occurring with extended residence in Antarctica. PMID- 2318954 TI - Pulsatile cosecretion of estradiol and progesterone by the midluteal phase corpus luteum: temporal link to luteinizing hormone pulses. AB - Using recently defined analytical tools that permit quantitative and integrated assessments of pulsatile activities of two or more hormones, we have examined the coincidence of pulses of estradiol (E2), progesterone (P4), and LH determined in blood withdrawn at 15-min sampling intervals for a duration of 24 h in each of 15 women during the midluteal phase of the human menstrual cycle. The occurrence of E2 and P4 pulses is simultaneous, as their peaks were maximally correlated at zero time lag (P less than 10(-4], and there were comparable periodicities for E2 (13.5 +/- 0.7 pulses/24 h) and P4 (11.2 +/- 0.7 pulses/24 h). This coupling of E2 and P4 pulses suggests cosecretion by the mature corpus luteum. These E2 and P4 pulses are significantly coupled with LH pulses, with a lag time of about 30 min and/or 45 min for P4 (P = 0.029) and 0 min and/or 15 min for E2 (P = 0.032). Further, when considered together, LH, E2, and P4 are found to be triply copulsatile (P = 0.0066). However, significant numbers of discrete pulses of P4 and E2 are observed without antecedent LH pulses, suggesting some degree of corpus luteum autonomy. In conclusion, orchestrated synchrony of pulsatile pituitary and ovarian (corpus luteum) signaling can be demonstrated by the coordinated temporal release of LH, E2, and P4 in normal cycling women. PMID- 2318953 TI - Progesterone and human chorionic gonadotropin do not stimulate placental proteins 12 and 14 or prolactin production by human decidual tissue in vitro. AB - To investigate the regulation of the synthesis and secretion of placental proteins-12 (PP12) and -14 (PP14) and PRL, explants and enriched preparations of stromal cells and gland cells obtained from 10 human early pregnancy decidua were preincubated in medium for 24 h (baseline), followed by incubation in medium with or without progesterone (0.02-32 mumol/L), hCG (10 and 100 ng/ml), or cAMP (0.25 1 mmol/L) in an atmosphere of 5% CO2-95% air at 37 C for another 96-120 h. Media were changed each 24 h, and PP12, PP14, and PRL levels were determined by RIA. Decidual explants, as well as their isolated cells produced detectable levels of PP12, PP14, and PRL in vitro. The gland cells synthesized and secreted about 30 times more PP14 than did stromal cells. After 96-120 h of incubation, the production of each protein by control cultures was increased 81-167% compared to the baseline (not significant). The secretion of these proteins in medium supplemented with progesterone or hCG was not significantly different from that in the control groups. 8-Bromo-cAMP significantly increased the secretion of PRL and PP12, but not PP14, by stromal cells compared to control values. We conclude that 1) PP14 is mainly produced by decidual gland cells; 2) progesterone at the concentrations used in our study does not stimulate production of PP12, PP14, and PRL in decidualized endometrium in vitro; 3) hCG does not stimulate the production of PP12 and PP14 in decidualized endometrium; and 4) 8-bromo-cAMP stimulates decidual stromal cell secretion of PRL and PP12. PMID- 2318955 TI - Spontaneous chemiluminescence activity of peripheral blood cells during experimental allergic neuritis (EAN). AB - In 30 Lewis rats the time course of spontaneous monocyte and granulocyte chemiluminescence activity (CLA) during myelin-induced experimental allergic neuritis (EAN) was studied. CLA of blood and peritoneal cells, and clinical, histopathological and electrophysiological findings were compared with data from 14 animals immunized with complete Freund's adjuvant and ten normal Lewis rats. About 12 days post-immunization there was a significant (p less than 0.003) rise in monocyte, but not in granulocyte CLA in EAN animals. CLA correlated significantly (p less than 0.02) with infiltrate formation in nerve roots, preceding clinical or electrophysiological signs of disease by 1-2 days. There was no increase in peritoneal monocyte CLA, which was consistently higher than blood monocyte CLA (p less than 0.002). PMID- 2318956 TI - Differentiation of the humoral immune response in herpes simplex encephalitis. AB - Six patients with herpes simplex encephalitis were investigated. Antibody activities against different viral antigens were determined in serum and cerebrospinal fluid with an enzyme-linked immunosorbent assay after adjusting both fluids to identical immunoglobulin G concentrations. In serum, the strength of the antiviral reaction remained low and no qualitative changes became detectable. In cerebrospinal fluid, at first locally synthesized antibodies were directed against the same antigens as in serum. Ten days later, the intrathecal reaction increased with additional antibodies against at least two antigens. Once established, this expanded heterogeneity remained stable during the course of the disease. PMID- 2318957 TI - Increased biogenic amine release in mouse hypothalamus following immunological challenge: antagonism by indomethacin. AB - Stimulation of the acute-phase response in mice by lipopolysaccharide, pokeweed mitogen, concanavalin A or interleukin-1 was associated with increased release of biogenic amines, serotonin and norepinephrine in the hypothalamus as indexed by their primary metabolites, 5-hydroxyindoleacetic acid and 3-methoxy-4 hydroxyphenylglycol, respectively. The increases in norepinephrine and serotonin turnover observed 4 h following systemic administration of interleukin-1 were antagonized by concurrent administration of indomethacin, a potent inhibitor of cyclooxygenase. These data suggest that the increase in norepinephrine and serotonin release in mouse hypothalamus during the acute-phase response to infection is partially mediated by the actions of arachidonic acid metabolites. PMID- 2318959 TI - Constant darkness enhances autoimmunity to type II collagen and exaggerates development of collagen-induced arthritis in DBA/1 mice. AB - The humoral function of the pineal gland is known to be strongly dependent on environmental lighting. Melatonin, the best characterized of the photo-dependent pineal hormones, has been reported to affect immune responses in mice. It has been hypothesized that the development of some types of psychosomatic and autoimmune diseases could be due to a disturbed release of this hormone. The present investigation was performed in order to evaluate effects of constant darkness (physiological stimulation of pineal melatonin synthesis) and constant light (physiological suppression of pineal melatonin synthesis) on the course of an experimental autoimmune model, the type II collagen-induced arthritis (CIA) in DBA/1 female mice. Mice kept in darkness develop more severe arthritis than those kept in constant light or in a normal dark/light rhythm (12 h light/12 h dark). Levels of anti-type II collagen antibodies were higher in mice kept in darkness, and the spleens of these animals were enlarged. Since castration of female DBA/1 mice enhances the severity of CIA, and since melatonin is known to exert effects on gonadal function, the experiment was repeated using oophorectomized mice. The same difference in arthritis severity between darkness- and light-exposed mice was obtained in this second experiment. We conclude that the exacerbation of arthritis in darkness is due to a darkness-induced change in levels of critical neurohumoral compound(s), that via gonadal independent mechanisms affect the autoimmune response. The exaggerated severity and chronicity of arthritis may be due to higher levels of melatonin in these animals. PMID- 2318958 TI - Analysis of T cell subsets after induction of experimental autoimmune encephalomyelitis in susceptible and resistant strains of rats. AB - T cell subsets in the peripheral blood, draining lymph node (DLN) and spinal cord lesions were analysed after the induction of experimental autoimmune encephalomyelitis (EAE) in susceptible (DA) and relatively resistant (AO) rats. In DA rats, a significantly higher number of CD4+ cells were generated in the DLN, in response to both nervous tissue antigens and complete Freund's adjuvant (CFA), compared to AO rats. In the peripheral blood of DA rats, the percentage as well as absolute number of CD4+ cells increased in the preclinical phase of EAE, but declined as the disease developed. The percentage of CD8+ cells decreased in both these phases of EAE. In resistant AO rats, however, there were no significant changes in the T lymphocyte subset percentages after EAE induction, although the absolute number of peripheral blood CD4+ cells again increased in the preclinical stage of EAE. In the CFA-treated control DA rats, the absolute number of CD4+ cells was increased in the preclinical phase. However, no decline comparable to that seen in diseased animals followed. It is concluded that the generation of CD4+ cells in response to this antigen is strain specific and, since the cells are released into the circulation, will affect the balance between the T cell subsets in the peripheral blood during the development of EAE. PMID- 2318961 TI - Common low-density lipoprotein receptor mutations in the French Canadian population. AB - Familial hypercholesterolemia (FH) has a frequency of 0.2% in most populations of the world. In selected populations such as the Afrikaners in South Africa, the Christian Lebanese, and the French Canadians, the disease is more frequent due to the founder effect. Previous studies demonstrated that a single mutation at the LDL receptor locus, the so-called French Canadian deletion, makes up 60% of the mutant genes responsible for FH in the French Canadian population. In this study, efforts were directed to determine if there were other common LDL receptor mutations in this population. Three missense mutations were identified and each mutation was reproduced and expressed in vitro. Two of the three mutations result in the production of an LDL receptor protein that is not processed to its mature form at a normal rate. Molecular assays were developed to detect the mutations directly, and the LDL receptor genes of 130 French Canadian FH heterozygotes were screened for the presence of the three missense mutations as well as two deletions. LDL receptor mutations were detected in 76% of individuals and 14% had one of the three missense mutations. PMID- 2318960 TI - Inhibition of bicarbonate absorption by peptide hormones and cyclic adenosine monophosphate in rat medullary thick ascending limb. AB - In vitro microperfusion experiments were performed to examine the effects of peptide hormones on bicarbonate and ammonium transport by the medullary thick ascending limb (MTAL) of the rat. Arginine vasopressin (AVP; 2.8 X 10(-10) M in the bath) reduced bicarbonate absorption by 50% (from 7.8 to 3.7 pmol/min per mm). AVP caused a similar reduction in bicarbonate absorption in tubules perfused with 10(-4) M furosemide to inhibit net NaCl absorption. Glucagon (2 X 10(-9) M in the bath) also reduced bicarbonate absorption (from 11.7 to 7.6 pmol/min per mm). The inhibition of bicarbonate absorption could be reproduced with either exogenous 8-bromo-cAMP or forskolin. With 8-bromo-cAMP (10(-3) M) in the bath, addition of vasopressin to the bath did not significantly affect bicarbonate absorption. PTH significantly inhibited bicarbonate absorption, but the extent of inhibition was less than that observed with either AVP or glucagon. Vasopressin had no effect on net ammonium absorption in MTAL perfused and bathed with 4 mM NH4Cl. These findings indicate that: (a) vasopressin, glucagon, and PTH directly inhibit bicarbonate absorption in the MTAL of the rat; (b) this inhibition occurs independent of effects on net NaCl absorption and appears to be mediated in part by cAMP; and (c) HCO3- and NH4+ absorption can be regulated independently in the MTAL. PMID- 2318962 TI - Allergic bronchial asthma due to Dermatophagoides pteronyssinus hypersensitivity can be efficiently treated by inoculation of allergen-antibody complexes. AB - Antigen-antibody complexes were made from allergens of the common house dust mite, Dermatophagoides pteronyssinus (Dpt) and an excess of purified autologous specific antibodies. These complexes have been used to treat Dpt-hypersensitive patients who suffered from chronic bronchial asthma. Clinical symptoms and medication intake were followed by filling in diary cards. Peak expiratory flow, measured four times a day, was also followed. Intradermal skin tests and bronchial challenge tests were performed with allergen together with an evaluation of nonspecific bronchial reactivity. Specific IgE and IgG antibodies were assayed after separation from the bulk of serum immunoglobulins by immunoadsorption. The study was carried out over two years according to a double blind protocol. Intradermal inoculation of antigen-antibody complexes resulted in a marked reduction of both clinical and medication scores. No systemic side effects were observed and only mild wheal and flare reactions were noted at the injection site. The treatment showed a drastic reduction of specific skin and bronchial reactivities with only marginal effects on nonspecific bronchial reactivity. Concentrations of specific IgE antibodies decreased significantly during the first weeks of treatment and remained at these lower values throughout the study. Specific IgG antibodies actually decreased in the majority of treated patients. The total amount of allergen used in this study was less than 1% of the amount currently used for conventional hyposensitization with the same allergen. These findings show that antigen-antibody complex inoculation is an efficient and safe means of treating allergic bronchial asthma and that the mechanism of action is likely to differ from conventional hyposensitization. PMID- 2318963 TI - Pathogenesis of Campylobacter fetus infections. Role of surface array proteins in virulence in a mouse model. AB - We developed a mouse model to compare the virulence of Campylobacter fetus strains with (S-plus) and without (S-minus) surface array protein (S-protein) capsules. In adult HA/ICR mice pretreated with ferric chloride, the LD50 for S plus strain 84-32 was 43.3 times lower than its spontaneous S-minus mutant 84-54. Seven strains of inbred mice were no more susceptible than the outbred strain. In contrast to the findings with Salmonella typhimurium by others, 3 X 10(7) CFU of strain 84-32 caused 90% mortality in C3H/HeN (LPSn) mice and 40% mortality in C3H/HeJ (LPSd) mice. High-grade bacteremia in HA/ICR mice occurred after oral challenge with S-plus C. fetus strains and continued for at least 2 d, but was not present in any mice challenged with S-minus strains. Bacteremia at 30 min after challenge was 51.6-fold lower in mice pretreated with 10 microliters of rabbit antiserum to purified S-protein than after pretreatment with normal rabbit serum. Challenge of mice with a mixture of S-minus strain 84-54 and free S proteins at a concentration 31.1-fold higher than found in wild-type strain 84-32 caused 30% mortality, compared with 0% with strain 84-54 or S-protein alone. These findings in a mouse model point toward the central role of the S-protein in the pathogenesis of C. fetus infection. The S-protein is not toxic per se, but enhances virulence when present on the bacterial cell surface as a capsule. PMID- 2318965 TI - Regulation of megakaryocyte phenotype in human erythroleukemia cells. AB - Induction of human erythroleukemia (HEL) cells with nanomolar tumor-promoting phorbol myristate acetate (PMA) diesters results in the synchronous acquisition of multiple markers of the megakaryocyte phenotype. Induced cells markedly increase their content of cytoplasm and show features of morphological maturation. At the ultrastructural level, PMA-treated cells show increases in cytoplasm, nuclear lobulation and nucleolar content, and free ribosomes. Limited numbers of cells also express alpha-granules and nascent demarcation membrane systems. Functionally, PMA-stimulated HEL cells express increased amounts of the megakaryocyte/platelet proteins: glycoprotein IIb/IIIa, platelet factor 4, von Willebrand factor, glycoprotein Ib, and thrombospondin. No changes are observed in antigenic markers of the erythroid (glycophorin A) or macrophage lineages (MO 1 or MO-2). The increases in antigenic expression are rapid, reaching maximum levels within 3-4 d under serum-free conditions. Treatment with PMA also abruptly (within 1-2 d) inhibits cellular division in these cells. Washout studies indicate that phorbols exert their effect within 18-24 h, the approximate cell cycle time for these cells. Consistent with proliferative arrest, c-myc proto oncogene transcripts begin to decline within 8 h of PMA treatment, although transcripts of c-myb are unaffected. Importantly, megakaryocyte differentiation is associated with endomitotic DNA synthesis (i.e., continued DNA synthesis in the absence of mitosis and cytokinesis), with HEL cells reaching a DNA content of 3-12 times that of unstimulated cells. Endomitosis is coordinately regulated with changes in antigenic expression and cell size such that those cells having the highest DNA content are the largest and also express the greatest levels of antigen. PMID- 2318964 TI - Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A dehydrogenase and its expression in isovaleric acidemia fibroblasts. AB - Isovaleric acidemia (IVA) is caused by a genetic deficiency of isovaleryl-CoA dehydrogenase (IVD). At least five distinct variant IVD alleles are known. We isolated five overlapping IVD cDNA clones from a human placenta cDNA library. They covered the entire coding region, except the initiation codon, and 587 bp in the 3'-noncoding region plus the poly(A) tail. The structure of the initiation site was identified by the study of genomic DNA and by the sequence comparison with rat IVD. Human IVD shared 89.6, 35.8, and 31.6% identical amino acid residues with rat IVD and human short and medium chain acyl-CoA dehydrogenases, respectively. In the Northern blot analysis of normal human liver and fibroblast poly(A)+ RNA, three mRNA species of different sizes (4.6, 3.8, and 2.1 kb) hybridized to IVD cDNA. Three mRNA species with similar sizes were also detected in five IVA fibroblast lines of different genotypes (variants 1, 1 X 2, 2, 3, and 5), suggesting that these variants are each due to a point mutation or small deletion. PMID- 2318966 TI - Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212). AB - Nerve growth factor (NGF) is a polypeptide that is required for normal development and maintenance of the sympathetic and sensory nervous systems. Skin has been shown to contain relatively high amounts of NGF, which is in keeping with the finding that the quantity of NGF in a tissue is proportional to the extent of sympathetic innervation of that organ. Since the keratinocyte, a major cellular constituent of the skin, is known to produce other growth factors and cytokines, our experiments were designed to determine whether keratinocytes are a source of NGF. Keratinocyte-conditioned media from the keratinocyte cell line PAM 212 contained NGF-like activity, approximately 2-3 ng/ml, as detected by the neurite outgrowth assay. Freshly isolated BALB/c keratinocytes contained approximately 0.1 ng/ml. Using a cDNA probe directed against NGF, we demonstrated the presence of a 1.3-kb NGF mRNA in both PAM 212 and BALB/c keratinocytes. Since ultraviolet radiation (UV) is a potentially important modulating factor for cytokines in skin, we examined the effect of UV on NGF mRNA expression. Although UV initially inhibited the expression of keratinocyte NGF mRNA (4 h), by 24 h an induction of NGF mRNA was seen. The NGF signal could also be induced by phorbol esters. Thus, keratinocytes synthesize and express NGF, and its expression is modulated by UVB and phorbol esters. PMID- 2318967 TI - Glucose transport and microvillus membrane physical properties along the crypt villus axis of the rabbit. AB - Both transport function and microvillus membrane physical properties evolve as the enterocyte matures and migrates up the crypt-villus axis. We isolated enriched fractions of villus tip, mid-villus, and crypt enterocytes from which microvillus membrane vesicles were prepared. Using this material we characterized the alterations that occur in microvillus membrane fluidity as the rabbit enterocyte matures and correlated these with kinetic studies of glucose transport. With increasing maturity the microvillus membrane becomes more rigid due to both an increase in the cholesterol/phospholipid ratio and alterations in individual phospholipid subclasses. Maximal rates of glucose transport were greatest in microvillus membrane vesicles prepared from mature cells. However, the glucose concentration producing half-maximal rates of transport (Km) was significantly lower in crypt microvillus membrane vesicles, suggesting that a distinct glucose transporter existed in crypt enterocytes. This distinction disappeared when differences between membrane lipid environments were removed. By fluidizing villus-tip microvillus membrane vesicles, in vitro, to levels seen in the crypt microvillus membrane, we observed a reduction in the Km of this transport system. These data suggest that the kinetic characteristics of the sodium-dependent glucose transporter are dependent upon its local membrane environment. PMID- 2318969 TI - Glomerular hypertrophy aggravates epithelial cell injury in nephrotic rats. AB - Glomerular function and structure were assessed after reduction of nephron number and restriction of protein intake in rats with adriamycin nephrosis. Rats received an injection of adriamycin and were divided into three groups with similar values for albuminuria after 4 wk. Group 1 rats then served as controls, group 2 rats were subjected to four-fifths renal ablation, and group 3 rats were placed on a low protein diet (8% protein) while group 1 and group 2 rats remained on a standard diet (24% protein). Micropuncture and morphometric studies were performed 10 d later. Estimated single-nephron albuminuria (SNalb) was increased by renal ablation in group 2 and decreased by protein restriction in group 3 (group 1, 20 +/- 2 micrograms/d; group 2, 68 +/- 7 micrograms/d; group 3, 12 +/- 1 microgram/d, P less than 0.05 groups 2 and 3 vs. 1). Increased SNalb was associated with increased glomerular volume in group 2 and reduced SNalb was associated with reduced glomerular volume in group 3. (group 1, 1.44 +/- 0.04 x 10(6) microns 3; group 2, 1.66 +/- 0.08 x 10(6) microns 3; group 3, 1.26 +/- 0.03 x 10(6) microns 3, P less than 0.05 groups 2 and 3 vs. 1). Increased SNalb in group 2 was not associated with an increase in glomerular transcapillary hydraulic pressure. The area of epithelial cell detachment from the peripheral capillary wall was markedly increased in group 2 but not perceptibly altered in group 3 (group 1, 16 +/- 5 x 10(2) microns 2; group 2, 65 +/- 17 x 10(2) microns 2; group 3, 18 +/- 5 x 10(2) microns 2; P less than 0.05 group 2 vs. 1). These studies show that glomerular hypertrophy is associated with increased epithelial cell detachment from the peripheral capillary wall and with increased remnant nephron albuminuria after reduction of nephron number in rats with established nephrosis. PMID- 2318968 TI - Adaptation to bacterial lipopolysaccharide controls lipopolysaccharide-induced tumor necrosis factor production in rabbit macrophages. AB - These experiments provide an explanation for the observation that two intravenous injections of lipopolysaccharide (LPS) spaced 5 h apart in rabbits cause tumor necrosis factor/cachectin (TNF) levels to rise in the blood only after the first LPS injection. Herein we show that treatment of elicited peritoneal exudate rabbit macrophages (PEM) with two doses of LPS given 9 h apart results in a marked reduction in TNF production by the second LPS exposure. This state of hyporesponsiveness is a result of adaptation to LPS, is induced by LPS concentrations that are 1,000-fold less than required to induce TNF production (picograms vs. nanograms), is characterized by a decrease in LPS-induced TNF mRNA without any change in TNF mRNA half-life, is not changed by including indomethacin in cultures, and is specific for LPS since LPS-adapted cells display a TNF response to heat-killed Staphylococcus aureus that is at least as good as that observed in control PEM. PMID- 2318970 TI - Primed stimulation of isolated perfused rabbit lung by endotoxin and platelet activating factor induces enhanced production of thromboxane and lung injury. AB - Bacterial sepsis often precedes the development of the adult respiratory distress syndrome (ARDS) and bacterial endotoxin (LPS) produces a syndrome similar to ARDS when infused into experimental animals. We determined in isolated, buffer perfused rabbit lungs, free of plasma and circulating blood cells that LPS synergized with platelet activating factor (PAF) to injure the lung. In lungs perfused for 2 h with LPS-free buffer (less than 100 pg/ml), stimulation with 1, 10, or 100 nM PAF produced transient pulmonary hypertension and minimal edema. Lungs perfused for 2 h with buffer containing 100 ng/ml of Escherichia coli 0111:B4 LPS had slight elevation of pulmonary artery pressure (PAP) and did not develop edema. In contrast, lungs exposed to 100 ng/ml of LPS for 2 h had marked increases in PAP and developed significant edema when stimulated with PAF. LPS treatment increased capillary filtration coefficient, suggesting that capillary leak contributed to pulmonary edema. LPS-primed, PAF-stimulated lungs had enhanced production of thromboxane B2 (TXB) and 6-keto-prostaglandin F1 alpha (6KPF). Indomethacin completely inhibited PAF-stimulated production of TXB and 6KPF in control and LPS-primed preparations, did not inhibit the rise in PAP produced by PAF in control lungs, but blocked the exaggerated rise in PAP and edema seen in LPS-primed, PAF-stimulated lungs. The thromboxane synthetase inhibitor dazoxiben, and the thromboxane receptor antagonist, SQ 29,548, similarly inhibited LPS-primed pulmonary hypertension and edema after PAF stimulation. These studies indicate that LPS primes the lung for enhanced injury in response to the physiologic mediator PAF by amplifying the synthesis and release of thromboxane in lung tissue. PMID- 2318971 TI - A major crossreactive idiotype associated with human antibodies to the Haemophilus influenzae b polysaccharide. Expression in relation to age and immunoglobulin G subclass. AB - Using idiotypic analysis, we examined the variable (V) region diversity of human antibodies specific for the capsular polysaccharide of Haemophilus influenzae b (Hib PS). A goat anti-idiotypic serum (anti-Id) was prepared against anti-Hib PS antibodies isolated from the serum of an adult immunized with Hib PS. The anti-Id bound donor anti-Hib PS antibodies and inhibited Hib PS binding of donor anti-Hib PS. In contrast, the anti-Id did not bind donor or pooled Ig depleted of Hib PS antibodies, nor did it inhibit antigen binding of human antibodies to pneumococcal PS's, meningococcal A PS or diphtheria toxoid. Crossreactive idiotype (CRI), as measured by anti-Id inhibition of Hib PS binding, was found in 74 of 98 subjects (76%) vaccinated with Hib PS at 1.7-57 yr of age. 60 of these 74 subjects had greater than 50% of their serum Hib PS-binding activity inhibited by anti-Id. No correlation was found between age and CRI expression. In subjects showing both IgG1 and IgG2 antibody responses, CRI was most frequently detected in both subclasses (71% of subjects). CRI was limited to either IgG1 or IgG2 in 19% of subjects, a finding suggestive of independent B cell lineages. 13 of 15 infants less than 17 mo of age, who responded to Hib PS-outer membrane protein conjugate vaccine, had greater than 50% of their serum anti-Hib PS antibody activity inhibited by anti-Id. The ability of native Hib PS and Hib PS oligomer to partially inhibit (60 and 35%, respectively) the binding between anti-Id and heterologous anti-Hib PS, indicated that some CRI determinants are in or near the combining site. In summary, our findings demonstrate a highly penetrant and frequently predominant CRI, which is expressed in both infants and adults. The results underscore the limited V region diversity of anti-Hib PS antibodies and indicate that CRI predominance is manifest early in ontogeny and is induced by both TI and TD forms of the Hib PS antigen. PMID- 2318972 TI - Hydroxyeicosatetraenoic acid metabolism in cultured human skin fibroblasts. Evidence for peroxisomal beta-oxidation. AB - To determine whether the peroxisome is responsible for hydroxyeicosatetraenoic acid (HETE) oxidation, 12- and 15-HETE oxidation was measured in normal and peroxisomal deficient skin fibroblasts from patients with Zellweger's (cerebrohepatorenal) syndrome. When incubated for 1 h with normal fibroblasts, reverse phase HPLC indicated that 24% of the 12-HETE radioactivity was converted to one major polar metabolite. Chemical derivatization followed by reverse phase HPLC and TLC indicated that this metabolite is 8-hydroxyhexadecatrienoic acid [16:3(8-OH)]. Similarly, 33% of the added 15-HETE was also converted to a more polar metabolite. Neither 12- nor 15-HETE were converted to any metabolites by the peroxisomal deficient (Zellweger) cells. No defect in HETE oxidation was found in other human fibroblast cell lines with diverse metabolic abnormalities. Zellweger fibroblasts accumulated increased amounts of 12-HETE, compared with normal fibroblasts. As in the normal cells, most of the 12-HETE incorporated into Zellweger fibroblasts was present in the choline and ethanolamine phosphoglycerides. Protein synthesis, lysosomal acid lipase activity, and mitochondrial butyrate oxidation were not impaired in the Zellweger fibroblasts. Since the Zellweger cells do not convert 12- and 15-HETE to oxidative metabolites, peroxisomes appear to be the cellular organelle responsible for HETE oxidation. PMID- 2318973 TI - Feedback regulation of bile-acid synthesis in the rat. Differing effects of taurocholate and tauroursocholate. AB - We studied the effect of the orientation of the 7-hydroxyl group in taurocholate (7 alpha) and tauroursocholate (7 beta) on the feedback regulation of bile-acid synthesis and its rate-controlling enzyme, cholesterol 7 alpha-hydroxylase, in bile-fistula rats. To ensure a constant supply of cholesterol and to label newly synthesized bile acids, RS[2-14C]mevalonolactone was infused intraduodenally at 154 mumol/h before and during bile-acid infusion. Mevalonolactone inhibited hydroxymethyl-glutaryl CoA reductase activity 90% but did not increase bile-acid synthesis and cholesterol 7 alpha-hydroxylase activity. When sodium taurocholate was infused at the rate of 27 mumol/100 g rat per h (equivalent to the hourly hepatic bile-acid flux), bile-acid synthesis decreased 82% and cholesterol 7 alpha-hydroxylase activity declined 78%. This inhibitory effect was observed in the absence of hepatic damage. In contrast, sodium tauroursocholate infused at the same rate did not decrease bile-acid synthesis nor cholesterol 7 alpha hydroxylase activity. Hepatic cholesterol content rose 36% with sodium taurocholate but did not change during sodium tauroursocholate administration. These results demonstrate that the feedback inhibition of bile-acid synthesis is mediated through the regulation of cholesterol 7 alpha-hydroxylase. In these experiments, taurocholate was a far more potent inhibitor than its 7 beta-hydroxy epimer, tauroursocholate. PMID- 2318974 TI - Plasma levels of C1- inhibitor complexes and cleaved C1- inhibitor in patients with hereditary angioneurotic edema. AB - C1- inhibitor (C1(-)-Inh) catabolism in plasma of patients with hereditary angioneurotic edema (HANE) was assessed by measuring the complexes formed by C1( )-Inh with its target proteases (C1-s, Factor XIIa, and kallikrein) and a modified (cleaved) inactive form of C1(-)-Inh (iC1(-)-Inh). This study was performed in plasma from 18 healthy subjects and 30 patients with HANE in remission: 20 with low antigen concentration (type I) and 10 (from 5 different kindreds) with dysfunctional protein (type II). Both type-I and type-II patients had increased C1(-)-C1(-)-Inh complexes (P less than 0.0001), which in type I inversely correlated with the levels of C1(-)-Inh (P less than 0.001). iC1(-)-Inh was normal in all type-I patients and in type-II patients from three families with increased C1(-)-Inh antigen, whereas iC1(-)-Inh was higher than 20 times the normal values in patients from the remaining two families with C1(-)-Inh antigen in the normal range. None of the subjects had an increase of either Factor XIIa C1(-)-Inh or kallikrein-C1(-)-Inh complexes. This study shows that the hypercatabolism of C1(-)-Inh in HANE patients at least in part occurs via the formation of complexes with C1- and that genetically determined differences in catabolism of dysfunctional C1(-)-Inh proteins are present in type-II patients. PMID- 2318975 TI - The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase. AB - Gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase all have potential roles in digestion of human milk triacylglycerol. To reveal the function of each lipase, an in vitro study was carried out with purified lipases and cofactors, and with human milk as substrate. Conditions were chosen to resemble those of the physiologic environment in the gastrointestinal tract of breast-fed infants. Gastric lipase was unique in its ability to initiate hydrolysis of milk triacylglycerol. Activated bile salt-stimulated lipase could not on its own hydrolyze native milk fat globule triacylglycerol, whereas a limited hydrolysis by gastric lipase triggered hydrolysis by bile salt-stimulated lipase. Gastric lipase and colipase-dependent lipase, in combination, hydrolyzed about two thirds of total ester bonds, with monoacylglycerol and fatty acids being the end products. Addition of bile salt-stimulated lipase resulted in hydrolysis also of monoacylglycerol. When acting together with colipase-dependent lipase, bile salt-stimulated lipase contributed also to digestion of tri- and diacylglycerol. We conclude that digestion of human milk triacylglycerol depends on three lipases with unique, only partly overlapping, functions. Their concerted action results in complete digestion with free glycerol and fatty acids as final products. PMID- 2318976 TI - Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit. AB - The effects of homologous plasma HDL and VHDL fractions on established atherosclerotic lesions were studied in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a 0.5% cholesterol-rich diet for 60 d (group 1). Another group of animals were maintained on the same diet for 90 d (group 2). A third group was also fed the same diet for 90 d but received 50 mg HDL-VHDL protein per wk (isolated from normolipemic rabbit plasma) during the last 30 d (group 3). Aortic atherosclerotic involvement at the completion of the study was 34 +/- 4% in group 1, 38.8 +/- 5% in group 2, and 17.8 +/- 4% in group 3 (P less than 0.005). Aortic lipid deposition was also significantly reduced in group 3 compared with group 1 (studied at only 60 d) and group 2. This is the first in vivo, prospective evidence of the antiatherogenic effect of HDL-VHDL against preexisting atherosclerosis. Our results showed that HDL plasma fractions were able to induce regression of established aortic fatty streaks and lipid deposits. Our results suggest that it may be possible not only to inhibit progression but even to reduce established atherosclerotic lesions by HDL administration. PMID- 2318977 TI - Stimulation of thrombopoiesis in mice by human recombinant interleukin 6. AB - To date, testing of various cytokines for the stimulation of blood cell production has not demonstrated a consistent effect on peripheral platelet levels. In this report, we provide evidence that human recombinant IL-6 increased platelet production in mice, as measured by both peripheral platelet levels and [75Se]selenomethionine (75SeM) incorporation into newly forming platelets. Peripheral white blood cell counts also were increased, but only to a modest extent, and hematocrit values were unchanged. A dose-response relationship between the amount of IL-6 administered and platelet count, 75SeM incorporation, and white blood cell count was demonstrated. Detectable megakaryocyte and granulocyte-macrophage colony-forming cells in mice that had received IL-6 also were increased in both bone marrow and spleen. These results demonstrate the ability of a purified, recombinant protein to stimulate platelet production in vivo. PMID- 2318978 TI - A human endothelial cell membrane protein that binds Staphylococcus aureus in vitro. AB - We have investigated S. aureus adherence to human endothelial cells utilizing an in vitro model. Staphylococcus binding to confluent endothelial cell monolayers was saturable in both dose and time response studies suggesting that the binding interaction was specific. We have developed a technique, based on the pH dependent affinity of iminobiotin for streptavidin, for the isolation of an endothelial cell membrane component that binds S. aureus, in vitro. A 50-kD membrane component was isolated and purified using this approach. This component was trypsin sensitive, periodate insensitive, and did not label with [3H]glucosamine. [35S]Methionine and [125I]iodine labeling confirmed that the protein was synthesized by and expressed on the endothelial cell surface. Functional binding studies demonstrated that staphylococci, but not endothelial cells, bound to the protein when immobilized on microtiter wells. Preincubation of staphylococci with the purified protein significantly (P less than 0.001) reduced staphylococcal binding to cultured endothelial cells. The capacity of S. aureus to colonize and invade endovascular surfaces may in part be a consequence of staphylococcal interaction with this endothelial cell membrane protein. PMID- 2318979 TI - Release of Ca2+ from the endoplasmic reticulum is not the mechanism for bile acid induced cholestasis and hepatotoxicity in the intact rat liver. AB - The hypothesis that monohydroxy bile acids exert their cholestatic and hepatotoxic effects via a sustained elevation of cytosolic [Ca2+] was tested in the isolated perfused rat liver. Infusion of the specific inhibitor of microsomal Ca2+ sequestration, 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) (25 microM for 10 min) produced efflux of Ca2+ from the liver and a sustained (20 min) increase in cytosolic [Ca2+] as indicated by the threefold increase in hepatic glucose output. Release of the endoplasmic reticular Ca2+ pool was demonstrated by the complete abolition of vasopressin- and phenylephrine-induced Ca2+ exchange between the liver and perfusate. Despite the profound perturbation of intracellular Ca2+ homeostasis produced by tBuBHQ, there was no decrease in bile flow and no evidence of hepatocellular injury (for 60 min), as indicated by lactate dehydrogenase release. In contrast, lithocholic acid (25 microM for 10 or 30 min) or taurolithocholic acid (5 microM for 10 or 30 min) produced an 80-90% inhibition of bile flow and a progressive increase in perfusate lactate dehydrogenase activity. During and after bile acid infusion, there was no change in Ca2+ fluxes between liver and perfusate, no stimulation of glucose output from the liver, and hormone-stimulated Ca2+ responses were preserved. It is concluded that the mechanisms for bile acid-induced cholestasis and hepatotoxicity in the intact liver are not attributable to changes in intracellular Ca2+ homeostasis, and especially not to prolonged release or depletion of Ca2+ sequestered in the endoplasmic reticulum. PMID- 2318981 TI - Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. AB - Fast atom bombardment mass spectrometry and gas chromatography-mass spectrometry were used to analyze bile acids in the body fluids of an infant (L.C.) whose liver contained no immunoreactive peroxisomal 3-oxoacyl-CoA thiolase. The profiles were compared with those of six patients with undetectable peroxisomes (Zellweger syndrome) and two siblings (N.B. and I.B.) whose defect of peroxisomal beta-oxidation could not be localized by morphological studies of peroxisomes or by immunoblotting of peroxisomal beta-oxidation proteins. 3 alpha, 7 alpha, 12 alpha-Trihydroxy-5 beta-cholestan-26-oic acid (THCA) was present in bile and plasma of all patients. However, bile from L.C., N.B. and I.B. contained unconjugated varanic acid (3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta cholestan-26-oic acid) as the major C27 bile acid, whereas bile from Zellweger patients contained only small amounts of varanic acid. In the bile from L.C. two isomers of varanic acid were present; in the bile from N.B. and I.B. a single isomer predominated. L.C., N.B., and I.B. all produced bile containing small amounts of (24E)-3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-en-26 oic acid [( 24E]-delta 24-THCA), its [24Z]- isomer, 3 alpha, 7 alpha, 12 alpha trihydroxy-5 beta-cholest-23-en-26-oic acid and 3 alpha, 7 alpha, 12 alpha trihydroxy-27-nor-5 beta-cholestan-24-one. The results provide evidence for peroxisomal pathways for cholic acid synthesis in man via THCA, delta 24-THCA and varanic acid and show that bile acid analyses can be used to diagnose peroxisomal thiolase deficiency. PMID- 2318980 TI - Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. AB - The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 micrograms/ml MM LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL. PMID- 2318982 TI - Atypical multinucleated cells form in long-term marrow cultures from patients with Paget's disease. AB - Although Paget's disease is the most flagrant example of a primary osteoclast disorder, little is known of osteoclast biology in this disease. In this report we have studied the formation of cells with the osteoclast phenotype in long-term cultures of marrow mononuclear cells derived from patients with Paget's disease, and compared these with similar cells formed in long-term marrow cultures from normal individuals, and with osteoclasts present in pagetic bone. Osteoclasts formed in pagetic marrow cultures resembled osteoclasts present in pagetic bone, but were distinctly different from osteoclasts formed in normal marrow cultures. Osteoclast formation was 10-20-fold greater in pagetic marrow cultures than in normal cultures. The multinucleated cells formed in cultures of pagetic marrow were much larger in size, were hyperresponsive to 1,25(OH)2 vitamin D, had more nuclei per cell, had increased levels of tartrate-resistant acid phosphatase activity and had ultrastructural features which were not seen in multinucleated cells formed from normal marrow mononuclear cells. These pagetic marrow-derived multinucleated cells formed large resorption lacunae on calcified matrices and cross-reacted with monoclonal antibodies which preferentially bind to osteoclasts. The multinucleated cells formed from marrow obtained from uninvolved sites in Paget's patients also displayed these abnormal features. PMID- 2318983 TI - A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus. AB - Family and population studies indicate that predisposition to insulin-dependent (type I) diabetes mellitus (IDDM) is polygenic. It has been shown that the absence of the aspartic acid in position 57 (Asp57) of the DQ beta chain is positively correlated to IDDM. However, Asp57-negative haplotypes do not always confer susceptibility and conversely, some Asp57-positive haplotypes seem to be disease associated. It has been suggested that other HLA class II sequences, probably belonging to the HLA DQA1 gene, confer susceptibility to IDDM. This report, based on extensive oligonucleotide dot blot hybridization of PCR amplified DQA1 and DQB1 genes, reinforces the importance of the Asp57-negative DQ beta chain, but also introduces the possibility that a DQ alpha chain bearing an arginine in position 52 (Arg52) confers susceptibility to IDDM. A molecular model of susceptibility to IDDM is proposed. This model strongly suggests that the disease susceptibility correlates quantitatively with the expression at the cell surface of a heterodimer, composed of a DQ alpha-chain bearing an Arg52 and a DQ beta chain lacking an Asp57. In view of the respective positions of the two residues and their charge, we might anticipate that both residues DQ beta Asp57 and DQ alpha Arg52 are critical for modulation of susceptibility, presumably via viral-antigenic peptide and/or autoantigen presentation. PMID- 2318984 TI - Gastrin-releasing peptide in human nasal mucosa. AB - Gastrin-releasing peptide (GRP), the 27 amino acid mammalian form of bombesin, was studied in human inferior turbinate nasal mucosa. The GRP content of the mucosa measured by radioimmunoassay was 0.60 +/- 0.25 pmol/g tissue (n = 9 patients; mean +/- SEM). GRP-immunoreactive nerves detected by the immunogold method of indirect immunohistochemistry were found predominantly in small muscular arteries, arterioles, venous sinusoids, and between submucosal gland acini. 125I-GRP binding sites determined by autoradiography were exclusively and specifically localized to nasal epithelium and submucosal glands. There was no binding to vessels. The effects of GRP on submucosal gland product release were studied in short-term explant culture. GRP (10 microM) significantly stimulated the release of the serous cell-specific product lactoferrin, and [3H]glucosamine labeled glycoconjugates which are products of epithelial goblet cells and submucosal gland cells. These observations indicate that GRP released from nerve fibers probably acts on glandular GRP receptors to induce glycoconjugate release from submucosal glands and epithelium and lactoferrin release from serous cells, but that GRP would probably not affect vascular permeability. PMID- 2318985 TI - Circulating high molecular weight IgG fibronectin complexes in myeloproliferative disorders. AB - The plasma of patients with myeloproliferative diseases was examined by polyethylene glycol (PEG) precipitation, analytical ultracentrifugation, and immunoaffinity chromatography for the presence of high molecular weight complexes of IgG and fibronectin. Abnormal circulating high molecular weight material was identified by ultracentrifugation in all patients. This was precipitated by PEG and was shown by exclusion chromatography to contain IgG in a high molecular weight form. Examination of plasma by immunoaffinity chromatography supported previous evidence for complex formation between IgG and fibronectin. These findings are further evidence that abnormal high molecular weight IgG complexes are a prominent feature of myeloproliferative disorders and implicate IgG fibronectin complex formation. PMID- 2318986 TI - Rheumatoid lymphadenopathy: a morphological and immunohistochemical study. AB - Sixteen lymph nodes from 14 patients with rheumatoid arthritis were examined immunohistochemically and morphometrically and compared with 10 control nodes showing follicular hyperplasia from patients without rheumatoid disease. Frozen material was available from nine patients and all controls. The nodes from patients with rheumatoid arthritis seemed to share characteristic features. The most striking of these was follicular hyperplasia in which the germinal centres, in spite of being quite large, showed relatively sparse proliferative activity. The nodes often showed infiltration of germinal centres by CD8 positive T lymphocytes and contained fewer IL2R positive cells in the paracortex than controls. These and other features may have some correlation with disease activity. Lymphadenopathy in rheumatoid arthritis may not just be a manifestation of joint inflammation but an active component of this multisystem disease and may reflect a widespread immunological abnormality. PMID- 2318987 TI - Hepatic iron in dialysed patients given intravenous iron dextran. AB - Five percutaneous biopsy and 17 necropsy liver specimens were analysed histologically and chemically for iron content in 22 patients receiving dialysis for chronic renal failure, 13 of whom were given intravenous iron-dextran. Brissot scores for assessing histological hepatic iron deposition and chemically measured liver iron concentrations correlated closely. Both variables depended on total cumulative dose of iron, and to a lesser extent, on time since the last dose. Fibrosis (seen in five patients) was minimal and non-specific. Electron microscopic examination showed that there was no generalised damage and confirmed the presence of iron in the hepatocytes in the form of ferritin. High liver iron concentrations, in excess of 1000 micrograms/100 mg dry weight, were seen in two patients. Four others given comparable cumulated amounts (18-23 g iron) did not have such high concentrations. Plasma ferritin concentrations were high in eight patients, some with and some without fibrosis. The risk of temporarily high iron deposition in the liver causing damage seemed to be minimal when weighed against the benefit of increased haemoglobin in most of the patients. Intravenous iron treatment merits further evaluation, particularly with the advent of erythropoietin treatment, which requires continuously available iron. PMID- 2318988 TI - Familial increased serum intestinal alkaline phosphatase: a new variant associated with Gilbert's syndrome. AB - Investigation of mild, inherited increased serum alkaline phosphatase activity partially combined with Gilbert's syndrome in one family showed, apart from a normal liver fraction, an intestinal isoenzyme pattern and an extra band in the agar electrophoresis. Analysis by agarose electrophoresis before and after incubation of neuraminidase showed that the extra fraction was an intestinal variant isoenzyme. The precise genetic background of the two disorders in this family could not be determined from the available data. Abnormal activities of (regular) intestinal alkaline phosphatase isoenzyme caused the increase in serum alkaline phosphatase in the absence of disease. PMID- 2318989 TI - Monitoring rejection after heart transplantation: cytoimmunological monitoring on blood cells and quantitative birefringence measurements on endomyocardial biopsy specimens. AB - Cytoimmunological monitoring and quantitative birefringence measurements were used as potential aids in diagnosing acute rejection after heart transplantation instead of histopathological assessment of the endomyocardial biopsy specimen alone. Cytoimmunological monitoring was based on morphological inspection and quantitation of mononuclear cells, particularly activated lymphoid cells. Quantitative birefringence measurements comprise a variable for myocyte contractile function. Its read out is the ratio of the degree of birefringence before contraction to that after. Cytoimmunological monitoring indicated significantly higher concentrations of activated lymphocytes in moderate or severe acute rejection, and quantitative birefringence measurements indicated decreased myocyte function during severe and resolved or resolving rejection. Cytoimmunological monitoring and quantitative birefringence measurements were diagnostically most useful in terms of sensitivity, specificity, and predictive value, when only data gathered before the first episode of acute rejection were considered. For cytoimmunological monitoring, diagnostic relevance was optimal when the data were expressed as relative proportions of activated lymphocytes. The quantitative birefringence measurements correlated best with analysis of the endomyocardial biopsy specimen when a cut off value of 1.25 was used. When both methods for diagnosing acute rejection were analysed together, no improvement in sensitivity (value 0.44) was found, but the specificity increased to 0.98 and the predictive value to about 0.80. It is concluded that cytoimmunological monitoring is a useful, non-invasive additional method for diagnosing the first period of acute rejection after heart transplantation and that quantitative birefringence measurements give valuable information on the extent of myocyte damage. PMID- 2318990 TI - Mucin depletion in inflammatory bowel disease. AB - The mucin and gland content of 26 rectal biopsy specimens--five normal specimens, 10 from patients with ulcerative colitis, and 11 from patients with Crohn's disease--were measured using a Quantimet image analyser. There was significantly less mucin in the groups with ulcerative colitis compared with either those with Crohn's disease or the normal controls. The difference in the gland content between the groups with ulcerative colitis and Crohn's disease and between the group with Crohn's disease and the normal controls did not reach significance. The results suggest that it is worth while assessing the mucin content of rectal biopsy specimens from patients with inflammatory bowel disease. In routine practice this assessment can be made by eye using a suitably stained section. PMID- 2318991 TI - Nucleolar organiser regions in kidney tumours and xanthogranulomatous pyelonephritis. AB - The AgNOR argyrophil technique was applied to clear cut examples of renal adenoma (n = 7), clear cell carcinoma (n = 9), and xanthogranulomatous pyelonephritis (n = 5). There was no significant difference between mean AgNOR counts per cell in adenomas and carcinomas, supporting the idea that there is a continuous spectrum of kidney tumours. Xanthogranulomatous pyelonephritis and clear cell carcinoma showed significant differences in mean AgNOR counts per cell, suggesting that the technique may be of use in distinguishing between these conditions, although further cases may need to be examined to confirm this. PMID- 2318992 TI - Radiation and other pathological changes in breast tissue after conservation treatment for carcinoma. AB - Histological changes in breast tissue after radiotherapy were evaluated. Changes in tissue from 17 patients previously treated for breast cancer by surgery and radiotherapy were compared with those seen in a control group treated with surgery alone. Vascular and epithelial changes were seen only in tissue from patients who had received radiotherapy and, therefore, seemed to be relatively specific; stromal changes were seen in both groups and seemed, therefore, to be non-specific. Epithelial atypia is of particular importance as it may be severe and be confused with recurrent malignancy. The presence of other changes associated with radiotherapy, particularly those in vessels, should help to avoid such misdiagnosis. PMID- 2318994 TI - Staphylococcus lugdenensis and endocarditis. PMID- 2318993 TI - Prognostic value of nucleolar morphometric variables in cytological breast cancer specimens. AB - In a retrospective study on cytological specimens from 86 patients with histologically confirmed invasive breast cancer, the prognostic value of nucleolar morphometric variables was studied and compared with nuclear variables. One hundred nuclei and their nucleoli on each slide were measured with a graphic tablet system at a total magnification of 2800 times using a stratified selection method. The number of nucleoli per 100 nuclei was also noted. Analysis of Kaplan Meier univariate recurrence free survival curves showed significant differences for eight nuclear features, nine nucleolar features, and three combined nuclear and nucleolar variables. The total number of nucleoli per 100 nuclei was the best single prognostic variable. Multivariate survival analysis (Cox regression model) showed that no other features provided additional prognostic information beyond that given by the total number of nucleoli. It is concluded that nucleolar morphometric variables assessed in cytological preparations have prognostic value in breast cancer, and the results of this study suggest that their prognostic value may exceed that of nuclear variables. PMID- 2318995 TI - Lack of in vitro activity of omeprazole against Campylobacter pylori. PMID- 2318996 TI - Sclerosing cholangitis and hepatic microvesicular steatosis in cystic fibrosis and chronic pancreatitis. PMID- 2318997 TI - Spiral shaped bacteria in gastric mucosa. PMID- 2318998 TI - Royal College of Pathologists' United Kingdom pilot study of laboratory accreditation. The College Accreditation Steering Committee. AB - The Royal College of Pathologists recently commissioned a pilot study to assess the feasibility, desirability, and cost of establishing a national scheme for laboratory accreditation in the United Kingdom. Using a format similar to that designed by the College of American Pathologists, eight inspectors visited 24 laboratories comprising the major disciplines of two district hospitals, two teaching hospitals, a specialised (paediatric) hospital and a private hospital. Nine were considered accreditable without reservation, but 15 had deficiencies identified of differing importance which needed to be corrected before accreditation could be awarded. Problems identified were variable, but none related to technical performance and many did not require extra resources to correct. The exercise was conducted without organisational difficulty at an approximate direct cost of 300 pounds per laboratory. The study shows that the format used could form the basis of a cost effective nationwide strategy. The type of problems identified suggest that such a strategy is more likely to succeed if it is organised from within the pathology professions. PMID- 2318999 TI - Laboratory costing system based on number and type of test: its association with the Welcan workload measurement system. AB - A laboratory costing system which recovers all costs against tests, rather than using both test and request charges, was developed. Methods of recovering costs of routine and emergency services, of capital investment in equipment, of instrument maintenance costs and of general hospital overheads were considered. The Welcan unit system of workload measurement was applied to a range of test procedures. Both the Welcan unit value and unit value adjusted fro calibration and quality control (Welcan based weighting) correlated only moderately with locally derived analytical time per test and correlated poorly with direct analytical cost per test. The correlation of direct analytical cost per test with total cost per test was much stronger than that of analytical time per test with direct analytical cost per test. The data suggest that neither Welcan unit values, Welcan based weightings, nor locally derived analytical time per test can truly reflect total resource consumption for the provision of a range of test procedures. This factor should be borne in mind when applying operational or performance indicators based on Welcan units. PMID- 2319000 TI - The influence of surface free energy and surface roughness on early plaque formation. An in vivo study in man. AB - Previous in vivo studies suggested that a high substratum surface free energy (s.f.e.) and an increased surface roughness facilitate the supragingival plaque accumulation. It is the aim of this clinical trial to explore the "relative" effect of a combination of these surface characteristics on plaque growth. 2 strips, one made of fluorethylenepropylene (FEP) and the other made of cellulose acetate (CA) (polymers with surface free energies of 20 and 58 erg/cm2, respectively) were stuck to the labial surface of the central incisors of 16 volunteers. Half the surface of each strip was smooth (Ra +/- 0.1 microns) and the other half was rough (Ra +/- 2.2 microns). The undisturbed plaque formation on these strips was followed over a period of 6 days. The plaque extension at day 3 and 6 was scored planimetrically from color slides. Finally, of 6 subjects samples were taken from the strips as well as from a neighbouring smooth tooth surface (s.f.e. 88 erg/cm2; Ra +/- 0.14 microns). These samples were analysed with a light microscope to score the proportion of coccoid cells, and small, medium, and large rods or fusiform bacteria. At day 3, a significant difference in plaque accumulation was only obtained when a rough surface was compared with a smooth surface. However, at day 6, significantly less plaque was recorded on FEP smooth (19.4%) when compared with CA smooth (39.5%). Between FEP rough (96.8%) and CA rough (98.2%), no significant difference appeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319001 TI - The prevalence of overhanging margins in posterior amalgam restorations and periodontal consequences. AB - The purpose of this study was to determine the prevalence of overhanging margins and associated periodontal status in 100 patients who had received completed treatment by final year dental students. Pockets, bleeding on probing and clinically detectable overhanging margins were recorded on all posterior teeth. Overhanging margins on approximal restorations were detected by use of bitewing radiographs. 1319 teeth were examined in which 2117 restored surfaces were evaluated. Of these, 1186 (56%) had overhanging margins. 62% of all approximal restorations had overhanging margins while 35% of buccal and 40% of lingual restorations had overhanging margins. 59% of new approximal restorations placed in previously unrestored surfaces had overhanging margins, and 595 overhanging margins identified on pre-treatment radiographs were still present on post treatment radiographs. 64.3% of pockets adjacent to overhanging margins were greater than 3 mm, compared with 23.1% of pockets adjacent to unrestored surfaces and 49.2% of pockets adjacent to restorations without overhanging margins. A similar association existed between restorative status and bleeding. 32% of pockets adjacent to overhanging margins bled on probing compared with 10.5% of pockets adjacent to unrestored surfaces and 21.6% of pockets adjacent to restorations without overhanging margins. Periodontal disease was more severe when overhangs were present. However, when approximal overhanging margins were adjacent to an edentulous space, the periodontal effects were lessened. When adjacent to neighbouring teeth, overhanging margins also significantly affected the periodontal status of those teeth. PMID- 2319002 TI - Effect of cigarette smoking on the transition dynamics in experimental gingivitis. AB - This paper reports the findings of an experimental gingivitis study conducted in smokers and non-smokers. 33 volunteers were examined and underwent prophylaxis during a period of 4 weeks. 28 subjects who showed a plaque index less than 0.20 on all prophylaxis occasions were permitted to continue in the study. Subjects then had their gingival status recorded, had their teeth polished and were requested to abstain from all oral hygiene measures for the following 21 days. After 5 days, 10 days and 21 days, plaque and gingival status were recorded using the criteria of the plaque index and gingival index. After the examination on day 21, the teeth were polished and oral hygiene was re-instituted. Following 2 weeks of supervised oral hygiene, recordings of plaque and gingival status were performed. At the initial examination, there was no difference between the clinical assessment of plaque and gingival status in smokers and non-smokers. Similar amounts of plaque accumulated in the 2 groups during the period of no oral hygiene, but smokers exhibited less gingival inflammation assessed clinically than non-smokers. This difference occurred as a result of an apparently lowered incidence rate and a markedly higher recovery rate in smokers compared to non-smokers. These findings may indicate that smokers for reasons yet unknown have a reduced capacity to mount and maintain an effective defense reaction to a given plaque challenge. PMID- 2319003 TI - Treatment of periodontal furcation defects. Coronally positioned flaps versus dura mater membranes in class II defects. AB - Mandibular class II furcation defects in 19 subjects were treated using 2 different methods of wound closure. In 16 of the defects, the wound was closed with a coronally positioned surgical flap secured by crown-attached sutures. In 15 of the defects, a collagenous membrane (freeze-dried dura mater) was placed to cover the exposed defect, followed by suturing of the surgical flap at the level of the alveolar crest. After use of a coronally positioned flap, an average of 70% of the defect volume became filled with bone, with complete closure by bone fill for 9 of the 16 treated defects. After use of dura mater membrane, 38% of the defect volume was filled with bone, with complete bony closure for 3 of the 15 treated defects. The results following use of coronally positioned flaps support our previous findings and the potentials of this technique. The results following use of dura mater membranes, together with recently reported risk for spread of virus with dura implants, do not justify the use of dura mater for these regenerative purposes. PMID- 2319004 TI - Clinical and histological findings in ligature-induced experimental periodontitis in dogs. A pilot study. AB - Prior to experimental periodontal regenerative procedures in animals, the process of destruction due to periodontitis is often simulated by placing ligatures around the necks of teeth. 2 models, one using cotton floss ligatures and the other elastic rubber ligatures, have been widely used. The aim of this study was to compare these 2 methods using clinical and histometric criteria. Premolars on both sides of the mandibular jaw were used in 2 beagle dogs. Periodontal tissue breakdown was induced during a 48-day period using cotton floss ligatures on one side of the mandible and contra-laterally by elastic rubber ligatures. At weekly intervals, the ligatures were changed and pocket depth and loss of probing attachment were recorded. All the ligatures were removed after 7 weeks. The animals were fed a soft, plaque-promoting diet during the experimental period. 20 days after ligature removal, the teeth were hemisected and the 2 roots extracted. From each tooth, 1 root was prepared for scanning electron microscopy and one for light microscopy. At the time of extraction, no differences regarding pocket depth or probing attachment level were found between the 2 groups. Root resorption was observed in all elastic ligature teeth, whereas only minor alterations at the root surface were observed on cotton ligature teeth. This finding may be of particular interest to investigators designing studies evaluating the healing sequalae of regenerative surgery in animals. As was observed in this study, root resorption can already be present in the pre experimental phase of periodontal tissue breakdown, particularly if elastic ligatures are used. PMID- 2319005 TI - Human histologic responses to guided tissue regenerative techniques in intrabony lesions. Case reports on 9 sites. AB - 9 sites of 8 teeth in 5 adults with severe periodontitis were treated by open surgical debridement followed by placement of 1 of 2 Teflon barrier membranes. Teeth were notched at both gingival margins and deepest visible calculus on the root. Barrier membranes were placed apical to alveolar crest and coronal to gingival notch. Flaps were sutured coronally and patients were placed on 1.2% chlorohexodine gluconate twice daily for 2 weeks, post-surgery. Subsequent to suture removal, patients returned for frequent plaque control until block removal. In order to observe early healing responses, 6 sites were harvested 5 to 8 weeks after surgical treatment. 3 additional sites were removed 14, 22 and 30 weeks respectively after surgical treatment. Histologically, new cementum was seen in a linear direction along root surfaces in 6 out of 9 sites (length of cementum = 0.5 to 1.7 mm). 3 sites showed no evidence of new attachment. At sites of cementogenesis, functionally-oriented fibers were inserted. The osseous seams opposite the new attachment often demonstrated osteogenesis. Regenerative responses were seen with both types of teflon membranes and were present as early as 5 weeks after surgery. PMID- 2319006 TI - The effect of mechanical oral hygiene procedures on bleeding on probing. AB - The purpose of the present study was to investigate the effect of mechanical oral hygiene procedures on bleeding on probing in relation to age and periodontal status. The study was carried out on 49 individuals divided into 7 experimental groups according to age and having been either treated for destructive periodontal disease or having an intact healthy periodontium. In order to eliminate any pre-existant gingival inflammation, all subjects received a carefully controlled oral hygiene program. At the start of the experiment, all subjects were instructed to abstain from oral hygiene procedures for 24 h. Thereafter, clinical baseline measurements were carried out, including bleeding on probing (BOP) using a standardized probing pressure. Next, all subjects cleaned their teeth according to their normal oral home care protocol using a multitufted toothbrush, toothpicks and interdental brushes. BOP scores were again assessed 30 min after completed tooth cleaning procedures. The results revealed a significant increase in BOP after the mechanical oral hygiene procedures in every individual in all experimental groups (p less than 0.05). Further analysis showed that the increase in BOP was independent of the periodontal status of the subjects. However the BOP scores after mechanical oral hygiene procedures were higher in the young age groups. It was concluded that the diagnostic predictability of BOP in the treatment of periodontal diseases might be affected by temporarily elevated BOP scores shortly after mechanical oral hygiene procedures. PMID- 2319007 TI - Disynaptic olfactory input to the hippocampus mediated by stellate cells in the entorhinal cortex. AB - Electrophysiological and anatomical studies indicate functional relationships between the olfactory bulb and the hippocampus, mediated by the lateral olfactory tract and perforant path. Fibres from the lateral olfactory bulb terminate in the molecular layer of the lateral entorhinal cortex, which contains stellate and pyramidal cells that project to the hippocampus. Therefore this study was performed to analyze whether a trineuronal, disynaptic chain connects the olfactory bulb and the hippocampus. In adult rats, Fast Blue was unilaterally injected into the septal hippocampus to label cells of origin of the entorhinohippocampal pathway. Lesions of the ipsilateral olfactory bulb induced anterograde terminal degeneration in the entorhinal cortex of the same animals. Fast Blue labelled, and thus hippocampally projecting entorhinal neurones in fixed vibratome slices of the operated brains were injected with Lucifer Yellow. Most of these neurones were stellate layer II and pyramidal layer III cells; in addition there were some sparsely spinous multipolar cells in layers II and III and sparsely spinous horizontal cells at the layer I/II border. Injected cells were photoconverted and processed for electron microscopy. Olfactory bulb lesions resulted in electron-dense degeneration of abundant terminal boutons in the outer zone of entorhinal layer I. The relative frequency of degenerating boutons decreased towards deeper zones of the layer. In the outer zone, degenerated terminals predominantly contacted dendritic spines. These contacts could be seen on injected stellate cells but not on pyramidal cells. This study shows that the area dentata of the rat is reached by disynaptic afferent input from the olfactory bulb and thus is likely to process olfactory information. Oligosynaptic pathways might provide the hippocampus also with visual and auditory inputs; such fast transmitted polysensory information could be essential for the proposed participation of the hippocampus in attention-related mechanisms. PMID- 2319008 TI - Muller cells in adult rabbit retinae: morphology, distribution and implications for function and development. AB - We describe the morphology and distribution of Muller cells in wholemounts of rabbit retinae labelled with either monoclonal antibodies (anti-Vimentin, 3H3, 4D6, and 4H11), or intracellular horseradish peroxidase. Several new features of Muller cell organization are noted. First, Muller cells appear to compose a single morphological class and their morphology varies systematically with retinal thickness. Second, in contrast to other retinal glia, Muller cells have a neuronlike distribution, with a peak density of 10,700-15,000 cells per mm2 at the visual streak and a minimum density of 4,400-6,000 per mm2 at both the superior and inferior retinal edges. There are 4.2 +/- 0.5 x 10(6) Muller cells per retina. Third, unlike in other species, rabbit Muller cells do not contact blood vessels, suggesting that they do not participate in the transfer of metabolites or in the blood:retinal barrier. Fourth, each Muller cell has a vitread endfoot about 20-40 microns in diameter composed of numerous fimbriae. The fimbriae from a single Muller cell generally contact several axon fascicles in the nerve fibre layer, and at each point along its length each fascicle is enclosed by the overlapping fimbriae from several Muller cells. Fifth, in the inner and outer plexiform layers, numerous filamentous branchlets extend 20 microns or more from the radial trunk, interweaving with branchlets from nearby Muller cells to form dense and continuous strata. In the ganglion cell layer and outer nuclear layer, Muller cell processes completely wrap neuronal somata, whereas in the inner nuclear layer they partially wrap somata. We discuss the functional and developmental implications of these observations. PMID- 2319009 TI - Postnatal development of preproenkephalin mRNA containing neurons in the rat lower brainstem. AB - Postnatal developmental changes of preproenkephalin (PPE) gene expression in rat brainstem neurons were studied by in situ hybridization histochemistry. On the basis of PPE mRNA expression, brainstem neurons were categorized into three types: 1) type I neurons were characterized by constant or increasing expression of PPE mRNA during postnatal development; 2) type II neurons started to express PPE mRNA several days after birth and continued to do so thereafter; and 3) type III neurons showed transient expression of PPE mRNA or stopped expressing the mRNA during early postnatal development. Type I PPE neurons were observed in diverse brainstem structures including the mesencephalic and pontine central gray matter, various reticular and raphe nuclei, the ventral tegmental area of Tsai, the interpeduncular nucleus, the nucleus of the brachium of the inferior colliculus, the ventral and dorsal tegmental nuclei of Gudden, the sphenoid nucleus, the laterodorsal tegmental nucleus, Barrington's nucleus, the parabrachial region, the lateral lemniscus and its related nuclei, the trapezoid nucleus, the rostral and ventromedial periolivary nuclei, the mesencephalic trigeminal and principal sensory trigeminal nuclei, the locus coeruleus, the subcoeruleus nucleus, the medial and spinal vestibular nuclei, the dorsal and ventral cochlear nuclei, the medial and lateral cerebellar nuclei, the Roller nucleus, and the intermedius nucleus of the medulla. Type II PPE neurons were found in the superior colliculus, the inferior colliculus, the central part of the dorsal tegmental nucleus, and as Golgi neurons in the granular layer of the cerebellum. Type III PPE neurons were located in the substantia nigra, the red nucleus, the superior olive, the motor trigeminal nucleus, the facial nucleus, the inferior olive, the dorsal motor nucleus of the vagus, and the hypoglossal nucleus. Such region-specific expression of the PPE gene during postnatal ontogeny suggests that rat brainstem PPE neurons may be involved in a variety of developmental events, such as cell proliferation, differentiation, and migration. PMID- 2319010 TI - Organization and actions of the noradrenergic input to the hamster's superior colliculus. AB - Immunocytochemistry using antisera directed against dopamine-beta-hydroxylase (DBH) was used to determine the organization of the noradrenergic (NE) input to the hamster's superior colliculus (SC). Immunocytochemistry for DBH was combined with retrograde transport of fluorogold (FG) to determine the sources of NE input to SC. Microiontophoretic techniques were used together with extracellular single unit recording and receptive field mapping techniques to determine the manner in which NE influenced the responses of individual SC neurons. The hamster's SC contained numerous DBH-positive fibers but no immunopositive cells. These fibers formed a plexus that was most dense in the lower stratum griseum superficiale (SGS). The density of DBH-positive fibers was very low in the stratum opticum (SO) and increased in density in the stratum griseum intermediale (SGI) and the other deep layers. When FG injections into the SC were combined with immunocytochemical detection of DBH, double-labeled cells were observed in the contralateral locus ceruleus. DBH-positive neurons were observed in several other portions of the mesencephalon and pons, but none of these were labelled with FG. The effects of NE iontophoresis were assessed for a total of 135 SC neurons. In 74% (N = 100), NE reduced spontaneous and/or stimulus evoked activity. In 3% (N = 4 cells), NE increased activity, and in 23% (N = 31 cells) it had no effect. These percentages were essentially the same for superficial layer visual cells and somatosensory neurons in the deep laminae. The effect of NE iontophoresis upon signal to noise ratios was assessed for 46 visual and 56 somatosensory neurons. For 54% (N = 25) of the visual cells and 16% (N = 9) of the somatosensory cells, NE iontophoresis decreased signal to noise ratios. For 13% (N = 6) of the visual cells and 21% (N = 12) of the somatosensory cells, NE iontophoresis increased signal to noise ratios. The effects of NE on the responsivity of SC neurons were antagonized by propranolol (86% of the 21 cells tested), sotalol (67% of the six cells tested), and atenolol (effective in the single cell tested). All these agents are beta-adrenergic antagonists. The single alpha-adrenergic antagonist that we evaluated, corynanthine, potentiated the effects of NE on the responsivity of the two SC neurons that we tested. PMID- 2319011 TI - Ultrastructural study of synapses at the time of neuronal migration and early differentiation in the tangential vestibular nucleus of the chick embryo in vivo. AB - The chick tangential nucleus is a primary vestibular nucleus whose two main neuron types migrate and begin to differentiate between 5 and 8 days in the embryo (gestation takes 20-21 days). Based on rapid Golgi impregnations of developing tangential neurons and growing fibers, we have identified ultrastructural counterparts and characterized interactions in the nucleus from 5 to 8 days. Developing tangential neurons received the earliest synapses at 5 days on their primitive processes and subsequently on their cell bodies by longitudinal fibers of unknown origins. In contrast, the primary vestibular afferents did not form identified synapses on the developing tangential neurons until 7 1/2 days. In conclusion, the earliest synapses in the tangential nucleus are formed by longitudinal fibers, which are probably not primary vestibular afferents. Since a specific class of fibers forms particular synapses on the tangential neuron precursors at predictable times prior to and during neuronal migration and also at the onset of differentiation, the role of these synapses in developmental events should be explored. PMID- 2319012 TI - Ultrastructure of the crossed isthmotectal projection in Xenopus frogs. AB - The nucleus isthmi (NI) of frogs is a relay for input from the eye to the ipsilateral tectum; each NI receives retinotopic input from one tectum and sends retinotopic output to both tecta. The crossed isthmotectal projection in Xenopus displays tremendous plasticity during development. Physiological and anatomical studies have suggested that the location at which a developing isthmotectal axon will terminate is determined by the correlation of its visually evoked activity with the activity of nearby retinotectal terminals. What structures could mediate such communication? We have examined quantitatively the ultrastructural characteristics of crossed isthmotectal axons and synapses in order to determine whether retinotectal axons communicate directly with isthmotectal axons via axo axonic synapses or whether the communication is indirect, e.g., via common postsynaptic dendrites. Our results support the conclusion that isthmotectal axons interact with retinotectal axons indirectly and that tectal cell dendrites are the critical site of interaction. PMID- 2319013 TI - Differential distribution of serotoninergic inputs on the goldfish Mauthner cell. AB - The morphology and distribution of the serotoninergic (5-HT) input to the Mauthner cell (M cell) of a teleost, Carassius auratus, were analyzed at the light microscopic level. Immunohistochemical methods revealed that 1) most fibers innervating the M cell originate from the ventral and lateroventral regions of the rhombencephalon; 2) two groups of fibers contribute to this innervation, thick ones (type I, 0.4-0.7 microns in diameter) with terminal endings and thin ones (type II, less than 0.2 microns) that issue numerous beaded varicosities 4 10 microns from the target cell and only occasional side endings contacting it; 3) the density of immunoreactive profiles is uneven over the whole cell and predominates on the ventral dendrite; and 4) the two sets of axons, although overlapping, do not have the same distribution. Specifically, both classes are present on the ventral dendrite, whereas type II fibers are the only ones observed on the soma, in the region of the initial segment of the axon, and in the vicinity of the lateral dendrite. Functionally identified inputs on the M cell also have a regionalized distribution, depending, for example, on whether they belong to excitatory or inhibitory networks. Thus we propose that 5-HT inputs have specific influences that are a function of their respective localization. PMID- 2319014 TI - Bulbospinal serotoninergic pathways in the frog Rana pipiens. AB - We combined retrograde fluorescent tracing with rhodamine immunofluorescence to identify the origin of serotoninergic neurons with descending projections to the spinal cord of frogs. After injections of Fluoro-gold into the spinal cord, retrogradely labeled immunoreactive serotoninergic neurons were detected in the caudal part of the brainstem from the level of the obex through the level of the VIII nerve. These doubly labeled cells were distributed along the midline throughout the rostrocaudal extent of the dorsal portion of the raphe nuclear region. Doubly labeled neurons were more numerous in the rostral than in the caudal part of the raphe area. The fluorescent tracer 1,1'-dioctadecyl-3,3,3'3' tetramethylindocarbocyanine perchlorate (DiI) was then placed in and around the middle and rostral raphe nuclear region. Anterogradely labeled fibers could be traced bilaterally in the lateral portion of the dorsal funiculus and the lateral and ventral funiculi. These fibers were seen terminating in the dorsal and ventral horns, as well as in the intermediate grey matter. After placement of DiI in the caudal raphe area, labeled fibers were found only in the intermediate grey and ventral horn. These findings suggest that the organization of bulbospinal serotoninergic pathways in the frog is similar to that of mammals, and that an isolated amphibian spinal cord preparation could be a useful model for pharmacological and physiological studies of the action of serotonin (5HT) in the spinal cord. PMID- 2319015 TI - Morphological organization of thalamocortical relay cells in the dorsal lateral geniculate nucleus of the North American opossum. AB - The morphology of relay cells in the dorsal lateral geniculate nucleus of the North American opossum was studied by using both Golgi-Cox material and cells stained from retrograde transport of horseradish peroxidase. In general, soma sizes were largest in the part of the nucleus representing the central retina and decreased from the middle third of the nucleus to the anterior to posterior poles. Relay cells labeled with horseradish peroxidase were found to constitute approximately 90% of the dorsal lateral geniculate nucleus cells and have larger soma diameters than most unlabeled cells. From morphometric analysis of several structural characteristics, three classes of relay cells were identified in both Golgi-Cox and horseradish peroxidase material. Type 1 cells, the predominant class, exhibited radially arranged primary dendritic fields, symmetrically organized relative to projection lines. Type 2 cells had relatively few primary dendrites, and complex dendritic fields that were oriented parallel to projection lines. Least numerous were Type 3 cells, which were characterized by relatively sparse dendritic fields oriented perpendicular to projection lines. An additional class of neuron, Type 4 cells, with small somata and sparse dendritic branching, was found only in Golgi-Cox material. Cells with Type 4 dendritic morphology were not found with retrograde horseradish peroxidase labeling and may represent interneurons. The classification of morphologically characterized cells in the opossum dorsal lateral geniculate nucleus was evaluated quantitatively with multivariate discriminant analysis. The classes are compared to physiologically identified Y-, X-, and W-like relay cells in the opossum and to relay cell classes in other species. PMID- 2319016 TI - Timing and patterns of astrocyte migration from xenogeneic transplants of the cortex and corpus callosum. AB - The timing, pattern, and pathway of astrocyte migration were investigated in vivo by transplantation of CD-1 mouse cerebral cortex (E13-14) or corpus callosum (P2 3) into neonatal rat cortex. A monoclonal antibody specific for a mouse astrocyte surface antigen (M2) was used to identify the location of the grafts and the migrated donor astrocytes. Within the host cortex, astrocytes from cortical grafts began migration at post-transplantation day (PTD) 7. Over the next 4 days, the most distant displaced donor cells were found progressively further away from the grafts, migrating at a rate of about 220 microns/day. After PTD 11, the migration rate for the farthest displaced donor cells slowed to 25 microns/day, and the cells appeared to stop at about PTD 16 at a distance of 1,100 microns from the edge of the graft. Astrocytes had a faster migration speed in the white matter and covered a longer distance (5 mm) than those in the gray matter, extending on occasion into the contralateral hemisphere. The patterns of astrocyte migration differed depending on local cues around the transplant. Donor astrocytes that had been implanted into the host cortex migrated toward the host cortical surface, sometimes in several radial lines. Astrocytes from grafts, especially callosal grafts, placed in the subcortical white matter migrated along the host fiber tracts. Many astrocytes transplanted into the hippocampus formed laminar patterns close to the hippocampal neuronal layers. These results suggest that the direction, pattern, and speed of astrocyte migration are influenced by local substrates in the host brain. PMID- 2319017 TI - Microbial ecology of interdigital infections of toe web spaces. AB - The microbial flora of normal and macerated interdigital toe web spaces was qualitatively and quantitatively identified in 77 patients. Dermatophyte fungi were recovered from 11% of normal patients compared with a 31% recovery from patients with macerated interspaces. Macerated interspaces were characterized by a greater recovery of organisms with pathogenic potential, with Staphylococcus aureus recovered from 36% of patients, Micrococcus sedentarius in 37%, Brevibacterium epidermidis in 54%, Corynebacterium minutissimum in 69%, and Pseudomonas species in 26%. The bacterial flora of macerated interspaces showed a significantly higher incidence of resistance to multiple antibiotics, and the recovery of antibiotic-resistant bacteria correlated with the recovery of dermatophytes that produce penicillin-like substances. The results of this study support the hypothesis that overgrowth of the resident bacterial population determines the severity of interdigital toe-web infections. PMID- 2319018 TI - The antibacterial efficacy of econazole nitrate in interdigital toe web infections. AB - Twenty-four patients with severe interdigital toe web infections and no evidence of dermatophyte colonization received randomized treatment with either econazole nitrate (Spectazole) or its vehicle. Of the patients treated with econazole nitrate, 88% had good to excellent responses, whereas no patient treated with the vehicle showed improvement. The total aerobic flora in the econazole group decreased 93%, with decreases in the large-colony diphtheroids, lipophilic diphtheroids, and gram-negative bacteria. The results of this study demonstrate that the antibacterial activity of econazole nitrate makes it an effective agent for the treatment of severe interdigital bacterial infections uncomplicated by dermatophyte colonization. PMID- 2319019 TI - Epidermolysis bullosa acquisita preceding the development of systemic lupus erythematosus. AB - In most cases of epidermolysis bullosa acquisita that occur in patients with systemic lupus erythematosus, the diagnosis of systemic lupus erythematosus is made before the development of blistering. We observed three patients with well documented epidermolysis bullosa acquisita that developed several years before the onset of systemic lupus erythematosus. One patient was producing anti-U1RNP autoantibodies at the time epidermolysis bullosa acquisita was diagnosed, and all five produced this antibody during the systemic lupus erythematosus phase of their illness. In addition, in all five cases of epidermolysis bullosa acquisita with systemic lupus erythematosus antibodies to double-stranded DNA ultimately developed, and severe systemic lupus erythematosus and lupus nephritis developed in four patients. Sera from 15 other patients with epidermolysis bullosa acquisita without overt systemic lupus erythematosus were analyzed for systemic lupus erythematosus-related autoantibodies. Four patients were found to have at least one such autoantibody. These findings further document an association between epidermolysis bullosa acquisita and systemic lupus erythematosus and suggest that patients with systemic lupus erythematosus who present with epidermolysis bullosa acquisita may represent a subset of lupus erythematosus that puts the patient at increased risk for the development of more severe systemic illness. Patients presenting with epidermolysis bullosa acquisita, especially those who are black or Hispanic, should be monitored for the development of potentially life-threatening systemic lupus erythematosus. PMID- 2319021 TI - Yellow nail syndrome. AB - The yellow nail syndrome is characterized by yellow, slow-growing nails in association with lymphedema, idiopathic pleural effusions, chronic bronchiectasis, and chronic sinusitis. We report two patients with yellow nail syndrome in whom spontaneous clearing of the nail changes occurred without resolution of the respiratory involvement. This observation suggests that nail changes may not result from the systemic manifestations. We also report for the first time the histopathologic findings of the nail matrix and bed, which demonstrate dense, fibrous tissue replacing subungual stroma with numerous ectatic, endothelium-lined vessels that are similar to that in the pleura in yellow nail syndrome. We hypothesize that primary stromal sclerosis may lead to lymphatic obstruction, thus explaining the clinical manifestations. PMID- 2319020 TI - Lichen planopilaris: a clinicopathologic study. AB - Three clinicopathologic variants of lichen planopilaris are described. The first is characterized clinically by individual keratotic follicular papules and histologically by a lichenoid inflammatory cell infiltrate confined to the follicular epithelium. The second variant consists of erythematous to violaceous plaques, some of which show follicular prominence; the histologic appearance is that of a lichenoid inflammatory cell infiltrate that affects both follicular and interfollicular areas. The third variant manifests as follicular papules of the scalp with concomitant or subsequent cicatricial alopecia. In this variant the histologic hallmark is a lichenoid, follicular and interfollicular inflammation, associated with or followed by scarring. Overlap among the three variants exists, and hence the concept of a disease spectrum ranging from pure follicular involvement without evidence of clinical scarring to cicatricial alopecia of the scalp is advocated. PMID- 2319022 TI - Facial skin complaints and work at visual display units. An epidemiologic study of office employees. AB - A questionnaire about skin rashes and their symptoms was sent to 3877 randomly selected office employees with different degrees of exposure to video display units (participation rate 96.6%). From this group 809 randomly selected persons were examined and interviewed. Itching and burning sensations with few visible signs were more common among persons who were highly exposed than among those in the nonexposed category. Objective facial signs were not significantly more common among persons in the highly exposed category. No dose-response effect was observed regarding the amount of video display unit exposure and objective skin signs. Unilateral skin rashes and skin malignancies were found in the same frequency in both highly exposed and the nonexposed persons. This study does not provide support for the hypothesis that video display unit work induces any recognized type of facial skin disease. PMID- 2319023 TI - Contact urticaria and anaphylaxis to natural latex. AB - Immediate allergic reaction to natural latex of Hevea brasiliensis has been well documented. We report 17 cases, all in women. Twelve had an anaphylactic reaction during surgery and five had contact urticaria. Reactions to prick tests done through a washed surgical glove and with natural latex were positive in 15 of 17 patients and in 16 of 16 patients, respectively; specific IgE was found in 12 of 17 patients. In 206 control subjects, results of a prick test through a surgical glove were negative. PMID- 2319024 TI - Livedo racemosa generalisata: an evaluation of thirty-four cases. AB - The results of investigations in 34 patients (28 women, 6 men) with livedo racemosa generalisata are presented. Neurologic or psychiatric symptoms were present in 28 patients. Nineteen patients had had one or more cerebral infarctions, and epilepsy (Sneddon's syndrome) developed in six. In most cases livedo preceded the neurologic disorder. In addition, many patients with livedo racemosa generalisata had Raynaud's phenomenon, cardiac abnormalities, or vascular changes in the ocular fundus. PMID- 2319025 TI - Squamous cell carcinoma antigen in patients with cutaneous disorders. AB - Serum levels of the tumor marker squamous cell carcinoma antigen (TA-4) were examined in patients with nonneoplastic dermatologic diseases. The majority of patients with significant disease had elevated levels of this antigen. The percentage of involved skin surface area correlated with serum squamous cell carcinoma antigen levels. Psoriasis and atopic dermatitis have different effects on squamous cell carcinoma antigen levels. Kidney failure also causes elevated levels. Squamous cell carcinoma antigen is not a reliable tumor marker in patients with squamous cell carcinoma at any site when these patients also have a cutaneous disorder that involves more than 2% of the skin surface area or when they have kidney failure. PMID- 2319026 TI - Complications of microwave hyperthermia treatment of psoriasis. AB - Three healthy men with psoriatic plaques unresponsive to tar, anthralin, and UVB were treated with 2450 MHz microwave heating for 30 minutes at 42 degrees C. Two patients had plaques over bony prominences. Pain developed in both patients, and one had a hypotensive episode during the first treatment. The third patient, whose plaque was greater than 2 cm and was not located over a bony prominence, completed the 5 weeks of biweekly treatments with complete resolution of the plaque and no complications. PMID- 2319027 TI - Pigmented nail bands and mucocutaneous pigmentation in HIV-positive patients treated with zidovudine. PMID- 2319028 TI - Acquired port-wine stain. PMID- 2319029 TI - Papular dermatitis of pregnancy: a case report. PMID- 2319030 TI - Lymphoepithelioma-like carcinoma in the skin. PMID- 2319031 TI - Parenteral pentazocine: cutaneous complications revisited. PMID- 2319032 TI - Cyclosporine therapy for severe systemic sclerosis associated with the anti-Scl 70 autoantibody. PMID- 2319033 TI - Aquagenic pruritus responds to propranolol. PMID- 2319034 TI - Biology of the sweat glands. PMID- 2319035 TI - Immunohistochemistry of intravascular papillary endothelial hyperplasia. AB - Intravascular papillary endothelial hyperplasia is an interesting endothelial proliferation, the nature of which has aroused some controversy. Five cases were studied by light microscopy and by immunohistochemistry using antibodies to Factor VIII-related antigen (FVIII-rAg), ferritin, alpha 1-antitrypsin, alpha 1 antichymotrypsin and vimentin and were compared with conventional intravascular organizing thrombi. The results show a similar progression of the immunophenotype of the endothelial cells in both entities: they are initially positive for ferritin, then acquire vimentin positivity and only display FVIII-rAg positivity in advanced ("mature") lesions. This suggests that intravascular endothelial hyperplasia is closely related to organizing thrombi and is probably a peculiar form thereof. PMID- 2319036 TI - Cutaneous metaplastic synovial cyst. AB - Metaplastic synovial cyst, a recently described entity, is histologically characterized by a cystic cavity lined by metaplastic synovial tissue that is often hyperplastic and protrudes into its lumen as villous structures. Clinically, these lesions resemble suture granuloma and develop at the site of previous surgical trauma. We have studied 4 cases of this unusual entity and have investigated the immunohistochemical profile in an effort to determine the nature and derivation of their lining tissue. One of our cases is unique since the lesion was associated with a basal cell carcinoma. A history of previous surgery was noted in one, and history of trauma in 2 of the 4 cases. Our immunohistochemical observations confirmed a mesenchymal derivation for the "synovial like villous structures" but non-availability of a specific "synovial" marker does not permit us to conclude with certainty the synovial nature of the metaplastic tissue. Cutaneous metaplastic synovial cysts are unique lesions which deserve attention and should be included in the differential diagnosis of cutaneous cysts. PMID- 2319037 TI - Immunohistochemical demonstration of ferritin in sweat gland and sweat gland neoplasms. AB - Using a rabbit anti-human liver ferritin antibody, we examined the binding patterns of this reagent in normal skin and observed a unique binding pattern limited to the outermost layer of the eccrine duct. Examination of a variety of sweat gland neoplasms revealed 2 distinct patterns. One was the binding of this antibody to the outermost layer of cells in the epithelial cords of syringoma, producing a characteristic ring when seen in cross-section. This pattern of binding did not occur in other neoplasms known to be related to the eccrine duct such as dermal duct tumor and eccrine poroma. Only sparse sporadic binding occurred in other eccrine and apocrine neoplasms. A second characteristic binding pattern, not related to that noted in syringoma and diffuse in pattern, was seen in acrospiroma and in a number of adnexal carcinomas. Diffuse ferritin expression has been described in malignant neoplasms in tissues other than skin. Diffuse ferritin staining of certain sweat gland neoplasms may be an indication of biologic activity and potential aggressivity of these neoplasms. PMID- 2319038 TI - Electron microscopic observations of dyskeratosis, apoptosis, colloid bodies and fibrillar degeneration after skin irritation with dithranol. AB - Dying cells undergo coagulative necrosis or apoptosis. In the skin, apoptosis is known to occur in graft-versus-host reactions, in lichen planus, during regression of plane warts and neoplasms, and after physical injury caused by ultraviolet light resulting in sunburn cells. The present study shows that primary skin irritation also causes apoptosis. Mild, or moderate-to-considerable, dithranol irritation of healthy uninvolved human skin caused focally coagulative necrosis of keratinocytes and also apoptosis of scattered keratinocytes, i.e. condensation of chromatin and cytosol, clumping of tonofilaments and budding of membrane-bound cell fragments. These apoptotic cell fragments were engulfed in the epidermis by macrophages. Colloid bodies were detected in the upper dermis and apparently represented nonphagocytosed apoptotic cell fragments that had dropped down from the epidermis. Dithranol also caused fibrillar degeneration of melanocytes and in some cases of Langerhans' cells, indicating that colloid bodies in the upper dermis could partly derive from these cell types. The significance of apoptosis in irritant contact dermatitis could be to maintain homeostasis of epidermis and counteract the hyperplastic response caused by irritant stimuli. Another possibility is that apoptosis was the response to an injury less severe than that causing necrosis. PMID- 2319039 TI - Desmoplastic trichilemmoma: histologic variant resembling invasive carcinoma. AB - A clinical and histologic review of 22 patients (13 males, 9 females) with cutaneous lesions classified as desmoplastic trichilemmoma is reported. Typically, the lesions occur as solitary dome-shaped papules on the face during (at least) the fifth decade of life. The average age was 64 years (range 19-89) with a median age of 66.5 years. The most frequent clinical diagnosis was basal cell carcinoma, and the most common sites were the lip, eyebrow and nose. Two lesions occurred in examples of nevus sebaceus of Jaddasohn. The proportion of desmoplasia varies, but is generally between 20% to 60% of the lesion. Ulceration is seen in a minority of lesions but when present, is closely associated with underlying desmoplasia. Desmoplasia may be seen in small, as well as large, trichilemmomas; it generally occurs centrally but at times may be seen peripherally. The appearance of strands of epithelial cells entrapped in dense fibrosis and hyalinization may mimic desmoplastic variants of squamous cell carcinoma and basal cell carcinoma. This appearance may be particularly troublesome when the desmoplasia occurs at the base of the biopsy specimen. Knowledge of this phenomenon and the search for more typical features of trichilemmoma such as clear cells and peripherally palisaded columnar cells upon a thickened, eosinophilic basement membrane will allow the correct diagnosis to be made. We believe that the desmoplasia occurs as a secondary change in pre existing trichilemmomas. PMID- 2319040 TI - An unusual presentation of a congenital benign apocrine hamartoma. AB - A case of an unusual benign apocrine hamartoma was studied by light microscopic, immunohistochemical, and electron microscopic methods. This tumor clinically showed a linear configuration and was located on the midline chest of a pubescent male. Microscopic studies revealed features of both a tubular apocrine adenoma and a syringocystadenoma papilliferum. PMID- 2319041 TI - Cutaneous metastases of a giant cell tumor of bone: case report. AB - A 47-year-old patient with the previous history of a giant cell tumor of the left femur presented with 3 cutaneous nodules located on the face. Histologic examination revealed skin metastases of a giant cell tumor of bone, with dermal and subcutaneous nodules characterized by multinucleate giant cells and mononuclear cells. The patient died 10 months later from widespread metastases to the lung and brain. A panel of enzymo- and immunohistochemical markers reactive and osteoclastic, fibroblastic and histiocytic determinants was tested on the cutaneous lesions. The results indicated osteoclastic lineage of the multinucleate giant cells whereas the mononuclear cells showed features of fibroblastic differentiation. Cutaneous metastasis from a giant cell tumor of bone is an extraordinary event and so far has only been reported once. PMID- 2319042 TI - Acquired immune deficiency syndrome. PMID- 2319043 TI - Attributional style in clinically depressed and conduct disordered adolescents. AB - We tested the reformulated learned helplessness theory of depression with adolescent inpatients (N = 63) who were diagnosed by Diagnostic and Statistical Manual of Mental Disorders (DSM-III; American Psychiatric Association, 1980) criteria as depressed, or conduct disordered, or both. Adolescents with major depression diagnoses differed from nondepressed adolescents with significantly lower attributional style scores for positive events. The study also evaluated the relation of self-reported depression, anxiety, and social maladjustment to attributional style. Subjects who reported more severe depression had a significantly lower composite score for internal, stable, and global attributions for positive events. The composite of internal, stable, and global attributions for negative events was not significantly related to either diagnosed or self reported depression. PMID- 2319044 TI - Psychological factors that predict AIDS high-risk versus AIDS precautionary behavior. AB - Men (N = 526) who patronized gay bars in three cities completed measures of sexual behavior covering the previous 3 months and psychological measures theoretically pertinent to AIDS risk. Thirty-seven percent of the sample reported engaging in unprotected anal intercourse, the behavior most strongly associated with transmission of human immunodeficiency virus (HIV) infection. Perceived peer norms concerning the acceptability of safer sex practices, AIDS health locus of control scores, risk behavior knowledge, age, and accuracy of personal risk estimation, but not personal HIV serostatus knowledge, were associated with high risk and precaution-taking behavior. PMID- 2319045 TI - Changes in energy balance following smoking cessation and resumption of smoking in women. AB - Caloric intake, resting metabolic rate (RMR), leisure-time physical activity, and sensitivity and preference for sweet taste were prospectively examined in 7 female smokers across 3 weeks during periods of normal smoking (Week 1), complete cessation (Week 2), and resumption of smoking (Week 3). Energy balance changed significantly across weeks, as caloric intake increased (largely as a result of alcohol consumption) and RMR decreased during cessation, followed by decreased caloric intake and increased RMR with resumption of smoking. Activity and taste sensitivity and preference remained unchanged. Smoking cessation may thus cause rapid change in energy balance, which is quickly reversed on resumption of smoking. PMID- 2319046 TI - Depression in British and American children and its relation to anxiety and fear. AB - The relations between the Children's Depression Inventory (CDI), the Revised Children's Manifest Anxiety Scale (RCMAS), and the Fear Survey Schedule for Children-Revised (FSSC-R) were examined in 327 British and 336 American children. Relations were similar for both samples of children, with depression more closely related to anxiety than to fear. In addition, the utility of the Kovacs (1981) recommended cutoff score (CDI greater than or equal to 19) for identifying extreme groups of depressed children was evaluated. Children who reported high levels of depression also reported high levels of anxiety and social evaluative fears. The findings are discussed in light of Watson and Clark's (1984) notion of negative affectivity. PMID- 2319047 TI - Methylphenidate and baseball playing in ADHD children: who's on first? AB - The effects of 0.3 and 0.6 mg/kg methylphenidate were analyzed in a double-blind, placebo-controlled, cross-over study in which 17 boys (ages 7.8-9.9 years) with attention deficit hyperactivity disorder (ADHD) played in baseball games. Drug effects were evaluated on children's attention during the game, as indicated by their on-task behavior on the field and their ability to answer questions about the status of the game at all times. Judgment during batting, batting skill during the game, and performance on skill drills prior to the game were also assessed as a function of medication. Results revealed that methylphenidate had a beneficial effect on attending during the game. PMID- 2319048 TI - A comparison of alprazolam and behavior therapy in treatment of panic disorder. AB - The results of a clinical outcome study (N = 57) comparing behavior therapy directed at panic disorder (panic control treatment [PCT]) with alprazolam were reported. These conditions were compared with a medication placebo and a waiting list control group. Patterns of results on measures of panic attacks, generalized anxiety, and global clinical ratings reveal that PCT was significantly more effective than placebo and waiting-list conditions on most measures. The alprazolam group differed significantly from neither PCT nor placebo. The percentage of clients completing the study who were free of panic attacks following PCT was 87%, compared with 50% for alprazolam, 36% for placebo, and 33% for the waiting-list group. Since alprazolam may work more quickly than PCT but may also interfere with the effects of behavioral treatment, these data suggest a series of studies on the feasibility of integrating these treatments and on the precise patterns and mechanisms of action of various successful treatment approaches to panic disorder. PMID- 2319049 TI - Evaluation of a treatment approach combining nicotine gum with self-guided behavioral treatments for smoking relapse prevention. AB - 1,218 smokers able to quit smoking for 48 hr were randomly assigned to one of 12 cells in a 4 x 3 fully crossed factorial experiment. A pharmacologic factor contained four levels: nicotine polacrilex (gum) delivered ad lib or on a fixed regimen, placebo gum, and no gum. A self-guided behavioral treatment factor contained three levels: self-selected relapse prevention modules, randomly administered modules, and no modules. Those receiving nicotine gum were more likely to be abstinent at the 2- and 6-month follow-ups. The fixed regimen accounted for most of the effect for gum. There was no effect for the relapse prevention module factor. Men and women showed a differential treatment response. Men who received nicotine gum were more likely to be abstinent at each follow-up (2, 6, and 12 months). No treatment was significantly better among women. We conclude that research on different gum chewing regimens is warranted and that further examination of possible gender differences in response to replacement therapy is needed. PMID- 2319050 TI - Behavioral changes after closed head injury in children. AB - This study provides a longitudinal follow-up of the behavioral adjustment of 45 children with mild, moderate, and severe closed head injuries. Two measures of behavioral adjustment, the Child Behavior Checklist (CBCL) and the Vineland Adaptive Behavior Scales (VABS), were obtained from a parent at the time of injury and at 6 and 12 months postinjury. The severely injured children obtained significantly poorer VABS scores than children with mild and moderate injuries over the year-long follow-up. In addition, on the CBCL, severely injured children had more school problems and engaged in fewer social activities than mild and moderately injured children. These results show that severe head injury in children was associated with declines in adaptive functioning, whereas scores for children with mild and moderate injuries did not differ, nor did they deviate from average levels at any follow-up interval. PMID- 2319051 TI - Characteristics of participants in a large group awareness training. AB - A study was conducted to assess the psychosocial characteristics of individuals who become involved in large group awareness training (LGAT) programs. Prospective participants in The Forum, which has been classified as an LGAT, were compared with nonparticipating peers and with available normative samples on measures of well-being, negative life events, social support, and philosophical orientation. Results revealed that prospective participants were significantly more distressed than peer and normative samples of community residents and had a higher level of impact of recent negative life events compared with peer (but not normative) samples. Prospective participants also held preparticipation values more similar to those espoused by the LGAT than peer or normative samples, and the three groups failed to be distinguished by their levels of social support. The implications of the findings are considered for understanding participation in LGATs and other self-change promoting activities. PMID- 2319052 TI - Effects of systemic fluoride on the morphology of occlusal grooves of primary and permanent molars. AB - Molars developed in the presence of systemic fluoride have been judged to have shallow grooves and short cusps. In this replication study, however, both water fluoridation and fluoride supplementation had no significant effect on the groove widths or depths. PMID- 2319054 TI - Accuracy of clinical diagnosis for the detection of dentoalveolar anomalies with panoramic radiography as validating criterion. AB - It is noteworthy that little attention has been paid to the balance between economy, discomfort, and risk to the patient (costs) and the clinical significance (benefit) of panoramic radiography as a routine screening procedure. This study used orthopantomographs to validate clinical detection of dentoalveolar anomalies in young children. It appears that 439 children (67 percent) were exposed without benefit from the radiography. PMID- 2319053 TI - A radiographic investigation of third-molar development. AB - In view of limited investigations it was considered worthwhile to determine the impact of race, age, and gender on the development and calcification of third molars. Results showed that calcification of third molars could be estimated by observing one quadrant. The crown calcification process begins and is completed earlier in blacks. There were no significant gender differences. PMID- 2319055 TI - Eruption cysts: a retrograde study. AB - A retrograde study was done using laboratory data. Most eruption cysts occurred in the maxilla. The findings in this study were in direct contrast to those of previously published studies. PMID- 2319056 TI - Premature eruption of the premolars. AB - This paper presents a variety of cases in which very early loss of abscessed primary molars caused early eruption of the permanent successors. Clinical sequelae including ectopic eruption, alteration of eruption sequence, arch-length inadequacy and tooth impaction are illustrated by five case reports. PMID- 2319057 TI - Utah dentists sealant usage survey. AB - After a statewide survey of dentists to determine how many were using sealants, the Utah Department of Health, Dental Health Bureau developed and began implementing a sealant-education program in 1982. The extent of reported usage increased from 48 percent in 1982 to 98 percent in 1987. Routine use increased from 10 percent to 48 percent. PMID- 2319058 TI - Anodontia of the permanent dentition: fourteen years after initial diagnosis. AB - The congenital absence of teeth, total anodontia, may involve both the primary and permanent dentitions. This paper updates the dental history of a twenty-eight year-old Greek-American woman first reported in 1977 by Herman and Moss, when she was fourteen. Five complete sets of dentures had been made for her in thirteen years. Treatment was more complex due to an underdeveloped maxilla and a prognathic mandible. PMID- 2319059 TI - Precocious puberty in a monozygous twin: report of case. AB - This report describes some effects of premature production of sex hormones observed in a boy with precocious puberty. The data presented are compared with corresponding skeletal and oral factors in an unaffected monozygous twin brother. PMID- 2319060 TI - Society expects enrichment. PMID- 2319062 TI - Bacteremia and dental treatment. PMID- 2319061 TI - In vivo fluoride uptake in enamel and dentin from fluoride-containing materials. AB - The ability of fluoride-containing materials to deposit fluoride into the cavity walls could be a measure of their anticariogenic properties. Great penetration depths of fluoride were found in all groups in this study, with deeper penetration in dentin compared to enamel. PMID- 2319063 TI - North Carolina dentist disciplined. PMID- 2319064 TI - When your patients ask about mercury in amalgam. PMID- 2319065 TI - A profile of women dentists. AB - This investigation examines female dentists' employment status, practice characteristics, annual income, job satisfaction, familial status, and relationships with colleagues and staff. A questionnaire was constructed using a yes/no response, short answer, and multiple choice format. The instrument was mailed to a random sample of 2,000 female dentists in September 1988. Fifty-four percent (1,086) of the sample population responded to the single mailing. More than 80% are satisfied with their dental career and current practice arrangement. The majority of these women described their working relationship with male and female colleagues and staff as excellent. PMID- 2319066 TI - Etidocaine hydrochloride in surgical procedures: effects on postoperative analgesia. AB - Because early research has established the prolonged duration of the effects of etidocaine, this study was performed to determine whether the long-acting local anesthetic can reduce the need for postoperative analgesics after oral surgery. PMID- 2319067 TI - Mixed density lesion of the anterior maxilla. AB - A case of COC which developed as a mixed lucent-opaque lesion in the anterior maxilla of a young person is discussed from the standpoint of clinical and radiographic differential diagnosis. Current concepts of the pathology of the COC and EOGCT are discussed. PMID- 2319068 TI - DPG urges RDs to speak out on infant formula marketing practices. PMID- 2319069 TI - Cholesterol-saturated fat index: ESHA software has it, new egg data changes it. PMID- 2319070 TI - Conclusions questioned for behavioral weight control program. PMID- 2319071 TI - A call for revision of meal examples in pediatric textbooks. PMID- 2319072 TI - Minority recruitment and retention: a career ladder approach. PMID- 2319073 TI - The effects of variations in carbohydrate, protein, and fat content of the diet upon weight loss, blood values, and nutrient intake of adult obese women. AB - The effects on weight reduction of three different 1,200-kcal diets followed for a 10-week period were examined in adult, sedentary, overweight women. Diet patterns contained 25%, 45%, or 75% carbohydrate, with variations in fat and protein. Parameters evaluated and compared for each diet were body composition, cholesterol, triglycerides, blood urea nitrogen (BUN), uric acid, percent body fat, and nutrient intake. Each diet group contained at least 11 women. Behavioral approaches were used to ensure that subjects complied with the caloric intake and the dietary pattern. No significant differences were found in the parameters except for BUN, which was significantly greater in the 25% carbohydrate group. Each 1,200-kcal diet contributed to weight loss. Selection of a weight reduction diet can be designed around preferred food patterns and nutrition needs of individuals rather than a proportion of the energy provided by carbohydrate in healthy adult women. Practitioners may use this research to demonstrate to clients that body weight can be lost while following a variety of nutritious diets. PMID- 2319074 TI - Characteristics of diet among a culturally diverse group of low-income pregnant women. AB - This study reports on diet quality and variety in food selection among a culturally diverse group of 335 low-income pregnant Massachusetts women. The Index for Nutritional Quality (INQ), which is the observed nutrient density divided by the recommended nutrient density, was estimated for seven nutrients from data reported on food frequency questionnaires and diet recalls. Mean INQs for protein and vitamin C were above the recommended level of 1.0, whereas INQ for iron was 0.6 or less. Mean INQ for calcium was 1.2 for whites and between 0.9 and 1.0 for non-whites. When comparisons were made among ethnic groups by site of prenatal care, significant differences in INQ were found for all nutrients except iron and vitamin B-6. WIC participants had higher diet quality for protein, calcium, iron, and vitamin B-6 than did non-participants. Employed women had higher protein and zinc INQs than did unemployed women, and non-smokers had higher iron and vitamin B-6 INQs than did smokers. Variety was not significantly correlated with diet quality but differed (p less than .001) among site-specific ethnic groups. We conclude that there is a need for investigation of factors influencing dietary practices that are associated with sites of prenatal care. PMID- 2319075 TI - The association of pregnancy weight gain with the mother's postpartum weight. AB - The association between pregnancy weight gain and the mother's weight at intervals following delivery was studied using the records of two clinics serving low-income populations. All the prenatal patients on whom complete data were available for a 2-year period were used. The 158 pregnant women gained a mean of 12.9 kg during their pregnancies; 44% gained more than 13.6 kg and 25% gained less than 9.1 kg. Three months after delivery the women showed gains significantly greater than those experienced by a nonpregnant comparison group during a comparable period. Maternal weight gain was determined by subtracting the infant's birth weight from the mother's total gain during pregnancy. Weight changes at three periods postpartum were compared among maternal weight gain tertiles. Sustained weight gains resulted in 39% of the women in the upper tertile being newly classified as overfat 1 to 3 months postpartum. Women in the high tertile had retained significantly more weight up through the sixth postpartum month. We conclude that a significant portion of maternal weight gain is likely to be retained, putting some women at risk of obesity. PMID- 2319076 TI - Low-income pregnant adolescents and their infants: dietary findings and health outcomes. AB - Dietary and other health-related data were obtained for 99 low-income, pregnant adolescents aged 13 to 19 years and their infants who were enrolled in the Teen Pregnancy Service (TPS). The dietetic services provided through TPS are highlighted for this sample of teens, 97% of whom were eligible for the WIC program. Average gestational age at time of enrollment for prenatal care was 18 weeks; 59% of the sample was anemic (hemoglobin value less than 120 gm/L). The average number of servings teens consumed each day from the four food groups was as follows: bread/grain, 5.0; milk, 2.8; meat, 2.8; and fruit/vegetable, 2.3. Teens who were overweight before pregnancy had heavier infants (mean = 3,344 gm) than their underweight peers (mean = 2,770 gm). Teens who gained 24 lb or less during pregnancy and who gave birth to full-term infants had infants with significantly lower birth weights (mean = 3,094 gm, p less than .008) than those who gained at least 25 lb (mean = 3,356 gm). Teens who smoked also had infants with lower birth weights than teens who did not smoke. Most teens bottle-fed their infants (82%). On the basis of our data, we conclude that low-income pregnant teens are likely to be at dietary risk. Dietary work with low-income pregnant adolescents is challenging and requires a thorough knowledge base about adolescent pregnancy, coupled with the ability to adapt traditional dietary counseling practices to meet the unique needs of these clients. PMID- 2319078 TI - Assessing beliefs of older rural Americans about nutrition education: use of the focus group approach. AB - We used the focus group interview technique as a preliminary research step in developing a nutrition education intervention for rural seniors who, because of less than optimal eating habits and changing demographics, are an important target audience. Sixty-eight well, active, rural North Dakota seniors, 60 years or older, from communities of 2,500 or fewer people, participated in five focus groups conducted in late summer 1988. As a qualitative research approach, focus group interviews offer a means of obtaining in-depth information on a specific topic from representatives of a target audience in a discussion group atmosphere. Focus groups require careful preparation and structuring and should include a capable moderator, a prepared discussion guide, carefully recruited participants, and a comfortable setting. The process generated ideas that we are using to develop a health promotion nutrition intervention that will be a mailed-home approach, including use of incentives, social role models, cholesterol screening, and learning activities. The intervention relies on the interest and ability of seniors to make positive health changes. We conclude that the focus group approach is useful in developing nutrition education interventions. PMID- 2319079 TI - Federal nutrition services for American Indian and Alaska native elders. AB - American Indian and Alaska native elders have a poverty rate of 61% and a life expectancy between 3 and 4 years less than that of the general older U.S. population. In 1978, Congress enacted a separate title under the Older Americans Act to address some of the special needs of American Indian elders. Since enactment of specific provisions for American Indians, Congress has continued to amend the Older Americans Act to ensure that the nutritional needs of American Indian elders are addressed. Currently, federal nutrition services are provided to American Indian and Alaska native elders through both Title III, Grants for State and Community Programs on Aging, Part C, Nutrition Services, and Title VI, Grants for Native Americans, of the Older Americans Act. In fiscal year 1987, more than 52,000 American Indian and Alaska elders received meals from congregate nutrition sites and/or home-delivered meals. PMID- 2319077 TI - The use of itemized register tapes for analysis of household food acquisition patterns prompted by children. AB - This article describes a method of collecting and analyzing itemized grocery receipts for use in epidemiological studies. As part of a larger study of children's food acquisition and exercise habits related to cardiovascular disease, a sample of 50 families was asked to keep itemized grocery receipts for a 2-week period. To control for bias as a result of differences in food consumption and food acquisition, mothers were asked to log meals eaten away from home, food used from home production, and gifts of foods. Items on the receipts were coded according to food groups and whether they represented child-prompted purchases. The items were expressed in terms of the percentage of the food dollar each category represented. Data from the survey were compared with data collected in national surveys. The method was found to be relatively non-intrusive, easily carried out, and eliminated many of the problems associated with non-response, respondent burden, and recall characteristic of other food account methods. It is suggested as a feasible way of characterizing the family food environment in epidemiological studies. PMID- 2319080 TI - Elevated blood cholesterol: a risk factor for heart disease that decreases with advanced age. PMID- 2319081 TI - Dietary intake and dieting practices of bulimic and non-bulimic female college students. PMID- 2319082 TI - Dietary habits, health beliefs, and food practices of elderly Chinese women. PMID- 2319083 TI - How members perceive district associations: a case study. PMID- 2319084 TI - Position of the American Dietetic Association: nutrition and health information on food labels. PMID- 2319085 TI - A retrospective study of graduates of a coordinated internship/master's degree program. AB - The coordinated dietetic internship/master's degree program (CDI/MDP) was formed in 1965 as a consortium of three hospitals and a university combining a hospital internship and graduate degree program. As of 1984, there were 317 graduates. The purpose of this study was to determine the employment, professional activity, and further education profiles of graduates in a 20-year period. The critical path method (CPM) was used as the blueprint for the 6-month project in which 267 questionnaires were sent and 152 were returned. Findings on areas of practice of graduates of the CDI/MDP indicated that their employment generally follows the same rankings as those found in previous studies of internship, CUP, and Plan IV programs, except for greater frequency of employment in education. Activities in professional associations were notable, with many graduates serving as officers or committee members. Twenty-one percent of respondents have earned or are in the process of pursuing study beyond the master of science earned with the internship. This may indicate that students interested in completing an internship/master's program have a strong achievement orientation or that they have an unusually high regard for education. Our findings provide valuable data for understanding the career impact of advanced education combined with the internship. PMID- 2319086 TI - Topical ocular chloramphenicol: clinical pharmacology and toxicity in optometric practice. PMID- 2319087 TI - Diet and dyslexia. PMID- 2319088 TI - Establishing national research objectives in optometry. PMID- 2319089 TI - Keir v. United States. PMID- 2319090 TI - A comparison of diagnostic outcomes with and without pupillary dilatation. AB - To compare the quality of fundus evaluations conducted with natural and dilated pupils, 500 typical adult subjects, divided into five age categories, were examined using both techniques. Direct and monocular indirect ophthalmoscopes were used with the natural pupils; direct and binocular indirect scopes were used for the dilated examinations. Retinal anomalies were classified on the basis of posterior pole or peripheral location and whether the anomalies would require significant action by the doctor. Of the 32 posterior pole anomalies which required action, 38% were missed during the natural pupil examination; 51% of the anomalies not requiring immediate action were also missed. These miss rates, along with the 287 anomalies found in the periphery (20 of which required immediate action), suggest that dilation should be strongly considered for all patients so as to optimize the probability of detecting fundus anomalies. PMID- 2319091 TI - Assessment of accommodative facility using MEM retinoscopy. AB - Subjective testing of accommodative facility can be difficult with young or nonverbal children, and children with learning problems. A new technique to objectively assess accommodative facility using monocular estimation method (MEM) retinoscopy is described. The objective technique was compared to a subjective assessment of accommodative facility, and the techniques were in agreement 86% of the time. Possible clinical usefulness of the objective procedure is discussed. PMID- 2319092 TI - Distribution of refractive errors in patients from Dominica, West Indies. AB - A total of 779 consecutive private patients requiring spectacles for correction of refractive errors were categorized according to age, sex, occupation and type of refractive error. Virtually all patients (97.1%) were black. The relationship between age, sex, occupation and refractive error was determined and showed that refractive errors were approximately equally distributed between the sexes, but myopia was more common among those with nearpoint occupations. Data also showed that more of the elderly were hyperopic than myopic in contrast to the younger patients who were more often myopic. PMID- 2319093 TI - Corneal arcus as an indicator of hypercholesterolemia. AB - For many years, corneal arcus has been documented as a normal, age-related change. Recent literature implies that corneal arcus is associated with elevated cholesterol, especially in the young, but that the association is not apparent in the elderly. This study demonstrates corneal arcus, regardless of age, as an indicator of elevated serum cholesterol, and as such, a sign of increased risk for cardiovascular disease. PMID- 2319094 TI - The effect of size on paired 'C/D' estimations. AB - This article describes a comparative study of the accuracy of proportional ratio estimations on stylized optic nerve head targets by experienced optometrists, student clinicians and beginning optometry students. Within limits, these estimations approximate the perceptual and cognitive tasks involved in the clinical estimation of cup-to-disc (C/D) ratios. There was no significant difference (alpha = 0.05) in the accuracy of estimations relative to clinical experience. The overall frequency of exactly correct paired estimations (i.e., both horizontal and vertical correct) for the 16 stylized targets was 18.6%. In a subanalysis of the data, less than half (45.4%) of the estimations were within +/ .05 of the true "C/D" ratios. Statistically, observers were more accurate for the smallest targets and less accurate for the medium and larger targets. Potential clinical implications of these findings, relative to C/D ratio documentation in glaucoma diagnosis and management, are presented and discussed. PMID- 2319095 TI - Research and practice: a delicate partnership. PMID- 2319096 TI - Lateral ankle stabilization using bovine collagen material: xenograft bioprosthesis, model GR. AB - This is a combined research study including use of a reproducible technique for ankle stress x-ray examinations (both preoperatively and postoperatively) and the use of the bovine bioprosthesis tendon implant for stabilization and augmentation of the lateral ankle ligaments. The surgical technique is fully described and the follow-up results indicate that there is long-term ankle stability, and that patient acceptance is very high. PMID- 2319098 TI - Treatment of chronic, two-plane instability of the ankle joint: syndesmoplasty versus periosteal flap versus tenodesis. AB - Repair of chronic ankle instability is recommended by a step-to-step approach. Anatomic repair with ligamentoplasty or periosteal flap will result in complete range of motion of the foot, but with less stability (7.1 degrees talar tilt). The more unphysiologic tenodesis procedure should be done in long-standing cases and gross instability, with the risk of loss of motion (10 degrees supination in one third of the cases), but with the advantage of best mechanical stability (3.5 degrees talar tilt). PMID- 2319099 TI - Distal tibiofibular synostosis and late sequelae of an ankle sprain. AB - The late sequelae of an ankle sprain is described in the form of an acquired tibiofibular synostosis. A synostosis can result in loss of dynamic motion between the tibia and fibula, which may create decreased and painful ankle motion. A case report and surgical procedure is presented. PMID- 2319097 TI - Lateral hindfoot instability treated with the Evans tenodesis: a biomechanical analysis. AB - The stabilizing effect of the Evans tenodesis on movements in the tibiotalocalcaneal joint complex was studied in 10 amputation specimens, using a kinesiologic testing device. The tenodesis was tested following solitary lesion of the anterior talofibular ligament and after combined lesions of the anterior talofibular and calcaneofibular ligaments. All tenodeses were performed with the joint complex in the neutral position. Regardless of the extent of ligamentous damage, the tenodesis frequently restricted adduction and internal rotation to a level below that recorded at intact ligaments. Instability in external rotation in the joint complex and anteroposterior laxity of the talus were never completely reconstructed, regardless of what degree of flexion in the joint complex the tenodeses were tested. The study demonstrates that, if performed with the tibiotalocalcaneal joint complex in the neutral position, the Evans tenodesis cannot reconstruct normal hindfoot kinematics, irrespective of the extent of ligamentous damage. However, severe instability in adduction and internal rotation, both part of clinical supination, were effectively prevented by the tenodesis. PMID- 2319100 TI - Skin blade versus deep blade: a vehicle of contamination in podiatric surgery. AB - A total of 166 surgical blades consisting of control blades, skin blades, and deep blades were cultured from 50 elective podiatric surgical cases. Five blades from four cases cultured Staphylococcus epidermidis. The practice of changing from skin blade to deep blade to reduce contamination of a clean surgical wound is not supported by the data obtained in this study. PMID- 2319101 TI - Use of indium-111-labeled white blood cells in the diagnosis of diabetic foot infections. AB - The diagnosis of bone infection in the patient with nonvirgin bone is a diagnostic dilemma. This is especially true in the diabetic patient with a soft tissue infection and an underlying osteoarthropathy. The authors present a retrospective study using the new scintigraphic technique of indium-111-labeled white blood cells as a method of attempting to solve this diagnostic dilemma. PMID- 2319102 TI - Self-tapping screw fixation of the Austin osteotomy. AB - The authors present an alternative method of fixation for the Austin bunionectomy using the Richards self-tapping screw. A description of the screw and method of application is included. In more than 250 osteotomies fixated by this technique, no complications inherent to the self-tapping screw have been encountered. PMID- 2319104 TI - Isolated posterior malleolar ankle fractures. AB - The isolated posterior malleolar fracture is a genuine clinicopathologic entity, albeit a relatively rare one. Frequency of occurrence is approximately 1% of all reported ankle fractures. It can be mechanistically explained within the parameters of the Lauge-Hansen classification. An understanding of the mechanism of injury is crucial to the diagnosis of associated soft tissue injury and to the correct management of the entire complex of peritalar disruption. Two cases of isolated posterior malleolar fracture are presented. PMID- 2319103 TI - Combined anesthetic and surgical treatment of reflex sympathetic dystrophy following a healed crush injury of the foot. AB - Reflex sympathetic dystrophy is an often overlooked diagnostic cause of posttraumatic pain. After wound healing, persistent pain frequently is treated with continued analgesic administration, physical therapy, acupuncture, nerve blocks, psychotherapy and sometimes even ignored in hopes that either the pain or the patient will "go away." The authors relate successful evaluation and treatment of reflex sympathetic dystrophy in the case of a young man with disabling pain following a healed crush injury to his foot. PMID- 2319105 TI - Large osteochondroma of the foot. AB - The author introduces a case demonstrating pedal involvement of osteochondroma. Clinical, radiographic, and histologic characteristics are illustrated. Several years following tumor excision, the patient has returned to unrestricted activities. PMID- 2319106 TI - Regional differences in the response of cardiac cells to triiodothyronine administration across the left ventricle free wall of rat heart. AB - We have studied the effect of T3 administration (50 micrograms/Kg/day) on the phenotype expression of several glucose-metabolizing enzymes (hexokinase, HK, glucose-6-phosphate dehydrogenase, G6P-DH, aldolase, ALD, phosphofructokinase, PFK, lactate dehydrogenase, LDH) in the different myocardial layers of the left ventricle wall. In the control rats, most of these enzyme activities are uniformly distributed across the left ventricle wall, G6P-DH being the only exception. In the rats given T3 for 14 days, the mean levels of PFK, HK and ALD activities increased significantly. With regard to the transmural distribution patterns, that of PFK was unchanged, unlike those of HK and ALD which exhibited their maximum increase in activity in the midmyocardium or in the mid- and subepicardial myocardium. With LDH, a significant increase in activity was found in the subepicardial layers which escaped detection on the whole homogenate. It is concluded that the administration of thyroid hormone has different effects on enzyme phenotype expression of cardiomyocytes in different regions of the cardiac wall. PMID- 2319107 TI - Bromocriptine reduces rat thyrotropin beta-subunit mRNA stability. AB - We have examined the effect of orally administered bromocriptine on TSH beta subunit messenger (m)RNA in the anterior pituitary glands of Sprague-Dawley rats using in situ and dot-blot hybridization histochemistry. Quantitative in situ hybridization of pituitary sections demonstrated a 60% reduction in TSH beta subunit mRNA probe binding from rats fed a diet containing bromocriptine 10 mg/kg/day. This was confirmed by dot-blot analysis of nuclear and cytoplasmic pituitary extracts from the same tissue. Hybridization of cytoplasmic extracts of pituitary cells cultured under actinomycin D-induced transcription arrest showed that part of the effect of bromocriptine appeared to be mediated through a change in TSH beta-subunit mRNA stability and implies that the acute influence of dopamine on TSH metabolism may be transduced by control of TSH beta-subunit mRNA catabolism. This suggests a mechanism by which cells with relatively stable tissue specific mRNAs appear to respond rapidly to hormonal effects at the transcriptional level. PMID- 2319108 TI - Stimulation of liver mitochondrial alpha-glycerophosphate dehydrogenase activity by L-thyroxine in thyroidectomized rats: comparison with the suppression of pituitary TSH secretion. AB - The rate of liver mitochondrial alpha-glycerophosphate dehydrogenase (GPD) induction was compared to the suppression of pituitary thyrotropin (TSH) secretion in thyroidectomized rats submitted to prolonged administration of small amounts of L-thyroxine (T4). With both 350 and 530 ng T4/100 g bw/day, liver alpha-GPD activity remained at post-thyroidectomy level (mean +/- SE: 0.030 +/- 0.002 and 0.034 +/- 0.001 delta A/mg prot/min, respectively) throughout all experiment. A sharp increase in enzyme activity was observed after 3 weeks of treatment in rats receiving 715 ng T4 / 100 g bw / day (mean +/- SE: 0.086 +/- 0.003 delta A/mg prot/min). In contrast, serum TSH levels were lower than pretreatment values (199 +/- 8ng/dI) in rats receiving 350 ng T4/100 g bw/day (mean +/- SE: 104 +/- 15 ng/dI; t = 7.48, p less than 0.001), decreased progressively with increasing T4 doses (m +/- SE:530 ng T4/100 g/day = 36 +/- 7 ng/dI); after only 48 h of treatment and were not significantly modified thereafter. The data are in agreement with the hypothesis of a nonlinear relationship between the degree of thyroid hormone receptor occupancy and the rate of liver mitochondrial alpha-GPD induction. PMID- 2319109 TI - Lingual thyroid in two natural brothers. AB - Tc99m scanning because of hypothyroidism revealed a lingual thyroid in two natural brothers who had no family history of thyroid disease. No thyroid tissue was found in the neck. Further development under substitution therapy with levothyroxine was normal. The diagnosis of this rare disease in two natural brothers suggests that lingual thyroid may be inherited. PMID- 2319110 TI - Chronic treatment with a long-acting somatostatin analogue in a patient with intestinal carcinoid tumor: occurrence of cholelithiasis. AB - The long-acting somatostatin analogue SMS 201-995 has been used efficaciously in the therapy of metastatic carcinoid tumor, vasoactive intestinal peptide producing islet cell carcinoma, acromegaly, and TSH secreting pituitary tumors. We report the development of a gallstone in a patient treated for 23 months with a long acting somatostatin analogue for a metastatic carcinoid tumor. Symptomatic improvement and a reduction in the urinary excretion of 5-hydroxyindoleacetic acid occurred. There was no evidence of a gallstone on ultrasound and CT scan of the abdomen prior to somatostatin therapy. A progressively enlarging, asymptomatic gallstone developed during therapy. PMID- 2319111 TI - T4-thyroid storm after CT-scan with iodinated contrast medium. AB - A 62-year-old woman had thyroid storm 5 h after a CT examination (contrast enhancement with 65% meglumine amidotrizoate, Angiografin). At the time of admission to our hospital, serum T4 and serum free T4 levels were markedly elevated (29 micrograms/dl and 9.6 ng/dl, respectively); serum T3 and serum free T3 levels were within normal limits (144 ng/dl and 5.9 pg/ml, respectively). These findings suggest that thyroid storm can occur with excess T4 only (T4 thyroid storm), and that T4-thyroid storm can be caused by administration of iodinated contrast medium. PMID- 2319112 TI - Borderline iodine deficiency in Belgium. PMID- 2319113 TI - Atypical environmental factor in expressing type I (insulin-dependent) diabetes mellitus. PMID- 2319114 TI - Iodine prophylaxis in Yugoslavia. PMID- 2319116 TI - Political and economic determinants of insurance regulation in mental health. AB - This article studies determinants of two important sets of laws regulating insurance coverage for mental health care: mandated inclusion of minimum coverage for psychotherapy, and mandated coverage for psychologist services, the so-called freedom of choice (FOC) laws. Political market models are developed and estimated to examine the passage of mandates and FOC laws among all fifty states from 1968 through 1983. Findings indicate that a number of groups influence whether these laws are passed, including psychologists and the state, which acts both in its own interests as a direct provider of services and to protect the public's interest. A state's political system and socioeconomic environment also influence the likelihood of passage of these regulations. Our findings run counter to the assumption often made by policymakers and researchers that regulations exclusively serve the interests of providers. PMID- 2319115 TI - Total digoxin-like immunoreactive factor(s) in healthy population, uncomplicated term pregnancies and neonates. AB - Free digoxin-like immunoreactive factor(s) (DLIF) which may have a homeostatic role, as documented in different physiological conditions, but is generally undetectable in plasma from normal population. Total digoxin-like immunoreactive factor(s) (protein bound and free) can be estimated after plasma is heated. In this study, total digoxin-like immunoreactive factor(s) as measured in plasma in a well defined control population and compared to healthy term pregnant women and neonates, categories known to be associated with increased free digoxin-like immunoreactive factor(s) concentrations. The mean level of this factor(s) in the control group was 706 +/- 129 pg digoxin equivalent/ml (pg/ml) and was unaffected by age and sex. Significantly increased levels of total digoxin-like immunoreactive factor(s) were found in pregnant women and neonates (928 +/- 127 and 1242 +/- 367 pg/ml, respectively). We conclude that levels of total digoxin like immunoreactive factor(s) are increased in term pregnancies and neonates, similarly to its free form. However total digoxin-like immunoreactive factor(s) is detected in the normal population as a plasma component, contrary to its free form, which is generally undetectable. PMID- 2319117 TI - The labor impacts of policy change in health care: how federal policy transformed home health organizations and their labor practices. AB - Health care organizations are highly labor-intensive; policies designed to stimulate organizational change are likely to have labor impacts. This paper examines the labor effects of policy change in home health care. Major federal home care policy trends since 1980 have spurred the evolution of the typical home care provider toward greater organizational and market rationality. Greater managerial sophistication has introduced changes in management/labor relations. Survey data from the 1986 DRG Impact Study are used to show how the pressure of cost-containment policies has pushed agencies to cut labor costs by increasing workloads, managerial supervision, and control of the work process. Research on the effects of recent policy change in health care has to date focused primarily on potential client effects. Labor impacts are rarely examined and are poorly understood at the time that policy is made. Findings in this article suggest that these issues deserve greater, more systematic attention, because unanticipated labor impacts may prove to be significant impediments to the realization of intended policy goals. PMID- 2319118 TI - What to do about teen pregnancy? PMID- 2319119 TI - Bridging the gap between ethical theory and practical decisionmaking in medicine. PMID- 2319120 TI - Production and characterization of monoclonal antibodies to N-acetyl-aspartyl glutamate. AB - N-acetyl-aspartyl-glutamate (NAAG) is a putative neuromodulator/neurotransmitter in the mammalian nervous system. Immunohistochemical studies with polyclonal NAAG antisera have revealed immunoreactive neurons and processes in several brain regions. However, these antisera crossreact to some degree with N-acetyl aspartate (NAA), which is present in mM concentrations in brain, prompting the development of monoclonal antibodies (MAb) more specific for NAAG. By fusing spleen lymphocytes obtained from BALB/c mice pre-immunized with NAAG covalently linked to bovine serum albumin by carbodiimide with SP2/0-Ag 14 mouse myeloma cells, we produced three IgG2a (kappa) MAb which specifically reacted with NAAG. These MAb exhibited negligible crossreactivity with NAA or with structurally similar peptides, as shown by solid-phase radioimmunoassay. Antibody activity was absorbed out selectively by both NAAG-thyroglobulin conjugate and free NAAG. These MAb stained many nuclei of the medulla-pons and midbrain, mitral cells in the olfactory bulb, pyramidal neurons in sensorimotor cortex, locus ceruleus, and several cholinergic cranial nuclei. The staining pattern strongly correlated with NAAG levels determined by HPLC. Monoclonal antibodies significantly enhanced sensitivity of staining, allowing visualization of dorsal horn neurons in spinal cord, which were not readily detectable with polyclonal antiserum. Availability of these MAb now facilitates further clarification of the role of NAAG in the brain. PMID- 2319121 TI - A neutral pH silver development method for the visualization of 1-nanometer gold particles in pre-embedding electron microscopic immunocytochemistry. AB - The availability of 1-nm gold particles permits the use of a particulate label with standard pre-embedding electron microscopic immunocytochemical techniques. We have employed these particles to localize a synaptic vesicle protein, p65, and a growth-associated protein, GAP-43, in neuron cell cultures. To be detected by standard transmission electron microscopy, these ultra-small gold particles must be enlarged. We have applied a commercially available silver development kit (IntenseM), the method of Danscher, and a neutral pH development procedure which we developed to effect this enlargement. Although IntenseM permits development with good preservation of morphology, it is limited by lack of reproducibility and by variability of final particle size. The method of Danscher provides well controlled and reproducible enlargement, but is limited with respect to preservation of ultrastructural details. The neutral pH development procedure reproducibly enlarges gold particles with superior preservation of morphology. The use of this development procedure in conjunction with 1-nm gold probes should permit precise ultrastructural localization of a variety of intracellular antigens. PMID- 2319123 TI - Development of a quantitative histochemical method for determination of succinate dehydrogenase activity in autonomic neurons and its application to the study of aging in the autonomic nervous system. AB - An accurately validated method was developed for quantitative determination of succinate dehydrogenase (EC 1.3.99.1; SDH) activity in individual sympathetic neuron perikarya by microdensitometric measurement of an SDH-nitroblue tetrazolium-derived formazan final reaction product. Optimal incubation medium and reaction conditions were determined for measurement of reaction product in cryostat sections of rat superior cervical and celiac-superior mesenteric ganglia. The Beer-Lambert laws were verified for the ganglion tissue, and microdensitometric measurements (expressed as mean cell density readings; MCDR/min-1), characteristic of the Michaelis-Menten equation, enabled the results to be used for enzyme kinetic determinations of SDH activity. Km and Vmax values were obtained following Hans linear transformation of the readings. Between the ages of 6-24 months no significant variations in Km values were recorded, indicating an unchanged structure for SDH (overall mean Km = 0.083 +/- 0.055 mM). However, in both ganglia there were significant decreases (ranging from 43-54%) in Vmax values for SDH at 24 months. The overall mean Vmax value at 6 months was 4.01 +/- 0.61 (MCDR) and at 24 months was 2.07 +/- 0.76 (MCDR). This suggests that an overall decrease in metabolic activity takes place with age in sympathetic neurons of the rat superior cervical and celiac-superior mesenteric ganglia. PMID- 2319122 TI - Fluid-phase endocytosis by intrahepatic bile duct epithelial cells isolated from normal rat liver. AB - Although recent data from our laboratory have established the occurrence of receptor-mediated endocytosis in intrahepatic bile duct epithelial cells (IBDEC) isolated from normal rat liver, no studies have assessed the role of isolated IBDEC in fluid-phase endocytosis. Therefore, to determine if IBDEC participate in fluid-phase endocytosis, we incubated morphologically polar doublets of IBDEC isolated from normal rat liver with horseradish peroxidase (HRP, 5 mg/ml), a protein internalized by fluid-phase endocytosis, and determined its intracellular distribution by electron microscopic cytochemistry. Pulse-chase studies using quantitative morphometry were also performed to assess the fate of HRP after internalization. After incubation at 37 degrees C, IBDEC internalized HRP exclusively at the apical (i.e., luminal) domain of their plasma membrane; internalization was completely blocked at 4 degrees C. After internalization, HRP was seen in acid phosphatase-negative vesicles and in acid phosphatase-positive multivesicular bodies (i.e., secondary lysosomes). Small acid phosphatase negative vesicles containing HRP moved progressively from the apical to the basal domain of IBDEC. Pulse-chase studies showed that HRP was then discharged by exocytosis at the basolateral cell surface. These results demonstrate that IBDEC prepared from normal rat liver participate in fluid-phase endocytosis. After internalization, HRP either is routed to secondary lysosomes or undergoes exocytosis after transcytosis from the luminal to the basolateral cell surface. Our results suggest that IBDEC modify the composition of bile by internalizing both biliary proteins and fluid via endocytic mechanisms. PMID- 2319124 TI - Differential expression of cell surface antigens of canine keratinocytes defined by monoclonal antibodies. AB - Nine monoclonal antibodies (MAb) directed against cell surface antigens of canine keratinocytes define distinct keratinocyte subpopulations owing to the differential expression of these antigens during the process of differentiation and depending on the tissue location of the cells. There was distinct antigenic heterogeneity between the different layers of stratified squamous epithelium and between stratified squamous epithelial of different tissue origin. Two MAb reacted only with antigens expressed by esophageal mucosa. Three MAb bound to antigens on keratinocytes of the suprabasilar and granular layers of stratified squamous epithelia, and they crossreacted with the transitional epithelial cells of the urinary tract. Two MAb reacted with antigens only expressed on differentiated cells, superficially located in the stratified squamous epithelium. The use of these MAb as markers for keratinocytes in studies on the characterization and differentiation of keratinocytes, as well as in tumor diagnosis and allograft transplantation, is discussed. PMID- 2319125 TI - Characterization of the isolation membranes and the limiting membranes of autophagosomes in rat hepatocytes by lectin cytochemistry. AB - The isolation membranes and the limiting membranes of autophagosomes in rat hepatocytes were characterized by lectin cytochemistry using concanavalin A (ConA), Ricinus communis agglutinin 120 (RCA-120), and wheat germ agglutinin (WGA). We found that RCA-120, ConA, and WGA bind to these membranes. The distribution of the lectins on the isolation membranes was heterogeneous, mainly found on the rims, which we referred to as the peripheral dilated portion. When the rims fused and thus formed autophagosomes the apparent sites of fusion were strongly labeled by the lectins. After autophagosomes were transformed to autolysosomes by fusion with lysosomes, the limiting membranes became more densely and homogeneously labeled with the lectins. We previously reported that cytochrome P-450 does not exist on the limiting membranes of the autophagosomes. Taken together, these results suggest that the isolation membranes may originate not from endoplasmic reticulum membranes but from some post-Golgi membranes that contain complex type N and/or O-linked oligosaccharide chains. PMID- 2319126 TI - Quantitative assessment and reduction of long-term autoradiographic background. AB - Quantitative autoradiography can measure distribution patterns in an animal exposed to radiolabeled compounds. A comparison of autoradiographs of rat brain containing low levels of 14C showed that a highly variable background signal had been produced. This resulted in several overexposed autoradiographs which could not be quantitatively compared. The background, believed to be produced by light emanating from the phosphor coating in the X-ray cassette, was a major impediment because it hindered correct analysis of the specimen. This article details our experiments demonstrating the sources of variance contributing to background and offers methods for its reduction. We found that placement of black polyethylene plastic between the slides and phosphor in the X-ray film cassette minimized autoradiographic background and effectively eliminated the effects caused by inherently different levels of radioactivity in the glass slides. PMID- 2319127 TI - Glycosaminoglycans of bovine aorta endothelial cells: identification and localization by use of a platelet factor 4-fluorescein probe. AB - We utilized platelet factor 4 (PF4) conjugated to fluorescein to stain the proteoglycans of permeabilized fixed bovine aorta endothelial cells in monolayer culture. Treatment of the monolayers with chondroitin ABC lyase and/or a preparation from Flavobacterium heparinum was used to remove chondroitin sulfate and/or heparan sulfate before staining, with resultant separate identification and partial localization of these glycosaminoglycans. When PF4-fluorescein was utilized with untreated control monolayers, fairly uniform reticular, perinuclear, and cell surface fluorescence was seen. After treatment with chondroitin ABC lyase, fluorescence was retained only on the cell surface. In contrast, treatment with the F. heparinum preparation resulted in the loss of all cell surface fluorescence. Use of both glycosaminoglycan lyases together resulted in loss of essentially all the fluorescence. The cell surface heparan sulfate observed by fluorescence after removal of cell surface chondroitin sulfate appeared to be unevenly distributed, with a heavier accumulation at one pole of each cell. This technique offers a specific method for identification and partial localization of cell surface heparan sulfate. PMID- 2319128 TI - Requirement for B cells for activation of contrasuppressor T cells by type III pneumococcal polysaccharide. AB - Type III pneumococcal polysaccharide (S3) is unable to activate S3-specific contrasuppressor T cells (Tcs) in mice depleted of B cells by chronic anti-IgM treatment or in immune defective xid mice that lack the B cell subset required for anti-S3 antibody responses. The inability of S3 to activate Tcs in xid mice was shown to be due to a requirement of B cells for Tcs activation rather than to an absence of Tcs in xid mice. The B cells from normal mice that are required for Tcs activation apparently function to present the S3 Ag to Tcs. S3 physically coupled to spleen cells (S3-SC) prepared from normal BCF1 SC could activate Tcs in both xid and BCF1 mice whereas S3-SC prepared from xid SC or B cell-depleted BCF1 SC could not activate Tcs in either strain. B cell APC function was abrogated by 3000 R irradiation and by treatment of the B cells with either chloroquine or paraformaldehyde. Interestingly, B cells from mice previously immunized with S3 were unable to function in Tcs activation; preimmunization of B cell donors with an irrelevant Ag or with a T-dependent form of S3 had no effect on their ability to function as APC. These latter observations are discussed in terms of the in vivo persistence of polysaccharide Ag and their ability to induce B cell tolerance under the experimental conditions used for these experiments. The results of this study provide evidence that B cells play an important and apparently obligatory role in the activation of Tcs by S3; B cells apparently function to present Ag to Tcs, resulting in the activation of this regulatory T cell subset. PMID- 2319129 TI - The use of peptide analogs with improved stability and MHC binding capacity to inhibit antigen presentation in vitro and in vivo. AB - The identification of a core region for OVA 323-339, which is critical in determining binding to IAd, has enabled us to generate a series of analog peptides in which this core region was extended at both the N and C termini with different amino acid residues. When assessed for binding capacity, several peptides were shown to have increased affinity for IAd compared with the parent sequence, and in addition, some peptides had acquired binding specificities for class II MHC haplotypes not present for OVA 323-339. These peptides were next examined for their ability to inhibit T cell responses in vitro and in vivo. The correlation between binding and the ability to inhibit T cell activation in vitro was good. However, when assessed in vivo, it was clear that high Ia binding was not sufficient in itself to define the inhibitory capacity of a given peptide. That this discrepancy was due to differences in degradation of the core-extended peptides was suggested by 1) results from an inhibition of Ag presentation assay, in which the pulse period with Ag and inhibitor was extended to 20 h; and 2) direct analysis of peptide stability by using reverse phase HPLC. Finally, by protecting the peptide from degradation with N- and C-terminal substitutions of D amino acids, the inhibitory capacity of an unstable core-extended peptide in vitro could be greatly enhanced. These data indicate that the core extension approach may be one method by which antagonists for MHC class II molecules may be generated. PMID- 2319130 TI - Induction of human B cell differentiation by Fc region activators. II. Stimulation of IL-6 production. AB - Fc region fragments derived from the enzymatic cleavage of human IgG have been shown to induce human peripheral blood-derived B cells to differentiate into Ig secreting cells (ISC). The synthetic peptide p23, corresponding to residues 335 to 357 in the Fc region of human IgG1, represents a region of the molecule responsible for stimulation of ISC formation. Fc region-induced ISC formation requires at least two signals; one supplied by Fc region activators and one supplied by a T cell-derived factor(s). In this report we show that the coculture of human PBMC with pFc' or p23, results in the release of factor(s) that resemble IL-6 in its pattern of biologic activity. This conclusion is based on the observations that supernatants from Fc region-stimulated PBMC cultures contained increased levels of elements that scored as positive in two assays for IL-6: the B9.9 hybridoma growth and the CESS cell differentiation assays. Moreover, RNA from Fc region-stimulation PBMC contained increased levels of IL-6 cDNA hybridizable elements. Finally, it was observed that rabbit anti-IL-6 inhibited the ability of supernatants derived from Fc region-stimulated PBMC cultures to induce B9.9 cell proliferation as well as p23-induced ISC formation in intact PBMC cultures. Fc region fragments induce both monocytes and T cells to produce IL-6. Taken together, these results indicate that IL-6 is produced in Fc region stimulated PBMC cultures and is involved in B cell activation by these activators. PMID- 2319131 TI - The binding site of human C4b-binding protein on complement C4 is localized in the alpha'-chain. AB - C4b-binding protein (C4BP) is a multimeric plasma protein, which regulates the classical pathway of the C system. C4BP functions as a cofactor to factor I in the degradation of C4b and accelerates the decay rate of the C4b2a complex. We now demonstrate that C4b contains a binding site for C4BP, which is localized on the alpha'-chain of C4b. SDS-PAGE of C C4 and C4b both under reducing and nonreducing conditions was followed by a radiolabeled C4BP ligand blotting procedure. It was demonstrated that the C4BP binding site on C4b is localized on the alpha'-chain. In addition, we found C4BP binding to the alpha-chain of C4, which suggests that the binding site for C4BP becomes available after reduction of the C4 molecule. Direct binding of C4BP to the alpha- and alpha'-chains of C4 and C4b was demonstrated in a radio-labeled C4BP binding assay with the reduced and alkylated isolated chains. mAb against the alpha'-chain of C4b were prepared, characterized, and evaluated for their ability to block the binding of 125I-C4BP to C4b. Two mAb specific for the alpha'-chain of C4b were found that completely abolished C4BP binding to intact C4b. Other mAb recognizing both the alpha- and alpha'-chain of C4 and C4b demonstrated only minor inhibitory effect on the binding of C4BP to C4b. In conclusion, we have localized the C4BP binding site on the alpha'-chain of C4b and have demonstrated that this binding can be inhibited by mAb specific for the alpha'-chain. PMID- 2319132 TI - A conserved anti-DNA antibody idiotype associated with nephritis in murine and human systemic lupus erythematosus. AB - In order to identify unique structural features of pathogenic autoantibodies to DNA in SLE, a murine anti-anti-DNA (anti-Id) mAb (mAb 1C7) was produced in response to immunization of lupus mice with a syngeneic anti-DNA mAb (mAb 3E10). Immunization of lupus mice with mAb 3E10 inhibited production of native anti-DNA antibodies, suppressed development of lupus kidney disease (nephritis), and induced production of anti-anti-DNA (anti-Id) antibodies. mAb 1C7 bound F(ab')2 fragments of mAb 3E10, and it bound other murine anti-DNA mAb, but not murine mAb or polyclonal serum antibodies unreactive with DNA. Moreover, binding of mAb 1C7 anti-Id to mAb 3E10 was inhibited by DNA, suggesting anti-Id binding within or near the binding site for DNA. Furthermore, mAb 1C7 bound serum IgG immunoglobulins from 9/12 patients with lupus nephritis and serum anti-DNA antibodies compared to only 3/12 SLE patients with comparable serum levels of anti-DNA antibodies, but without nephritis (p = 0.04), and only 1/53 SLE patients without serum anti-DNA antibodies, 0/49 patients with rheumatoid arthritis, and 1/47 healthy subjects (p less than 0.001). These results provide evidence that mAb 1C7 identifies a conserved Id associated with anti-DNA antibodies in murine and human SLE and may be useful as a structural probe to characterize pathogenic anti-DNA antibodies in SLE. PMID- 2319133 TI - Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. AB - Recent studies show the importance of a single amino acid, L-arginine, as a necessary substrate for activated macrophage-mediated cytotoxic activity for tumor target cells and microbiostatic function for Cryptococcus neoformans. The present studies were carried out to determine the role of the L-arginine dependent macrophage effector function on the microbiostatic effects of activated macrophages on the obligate intracellular protozoan, Toxoplasma gondii. A guanidino methylated derivative of L-arginine, NGmonomethyl-L-arginine (NGMMA), a competitive inhibitor of the L-arginine-dependent effector pathway, virtually abolished the normally potent microbiostatic effect of macrophages for Toxoplasma gondii after activation of the macrophages in vitro by IFN-gamma and LPS or in vivo by i.p. injection of killed Corynebacterium parvum. Addition of supplemental L-arginine to the culture medium overcame the capacity of NGMMA to block activated macrophage-mediated microbiostasis of Toxoplasma. The ability of NGMMA to inhibit the microbiostatic capacity of activated macrophages for Toxoplasma gondii correlated with almost total inhibition of synthesis of nitrite, nitrate, and L-citrulline from L-arginine. Therefore, as is the case for tumor target cells and C. neoformans, the synthesis of inorganic nitrogen oxides from a terminal guanidino nitrogen atom of L-arginine appears to be essential for murine cytotoxic activated macrophage mediated microbiostatic capacity for T. gondii. PMID- 2319134 TI - Requirement of lipophosphoglycan for intracellular survival of Leishmania donovani within human monocytes. AB - The function of the lipophosphoglycan of Leishmania donovani parasites was investigated in human peripheral monocytes. In contrast to wild-type L. donovani which grow in monocytes, incubation of monocytes with two variant lines of L. donovani, defective in lipophosphoglycan expression, resulted in the entry of the variant cells into the monocytes and their subsequent destruction. Passive transfer of lipophosphoglycan to the variant cells led to prolonged survival in monocytes. These results indicate that lipophosphoglycan is required by the parasite for intracellular survival. To investigate one possible protective role of the glycoconjugate, preincubation of monocytes with a suspension of lipophosphoglycan and subsequent treatment of the cells with PMA or opsonized zymosan resulted in an attenuation of the oxidative burst; the attenuation effect was concentration dependent on the glycoconjugate and independent of preincubation time. Moreover, hydrophobic beads, coated with lipophosphoglycan, were phagocytized by monocytes and found to inhibit oxygen consumption in monocytes activated with PMA. These results suggest a possible relationship between the absence of lipophosphoglycan in the variant parasites and their inability to survive within monocytes. Although the precise molecular basis remains to be elucidated, the ability of lipophosphoglycan to impair the microbial oxidative response may be a contributing factor in its requirement for intracellular survival. PMID- 2319135 TI - Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation. AB - A cDNA clone encoding the human lymphocyte differentiation Ag CD38 was isolated from a mixture of four different lymphocyte CDNA libraries expressed transiently in COS cells and screened by panning with mAb. Transfected COS cells expressed a surface protein of Mr 46,000 that was similar to the native CD38 molecule expressed on the B cell line Daudi and the T cell leukemia HPB-ALL and which was recognized by each of the CD38 specific mAb HIT-2, T16, T168, HB7, 5D2, ICO-18, and ICO-20. The CD38 cDNA sequence predicts an unusual 30-kDa polypeptide with a short N-terminal cytoplasmic tail, and a carboxyl-terminal extracellular domain carrying the four potential N-linked glycosylation sites. The absence of significant homology with other known surface Ag including members of the Ig superfamily ruled out the possibility that CD38 was the human homologue of the murine Qa2 molecule as has been suggested previously. PvuII digests of human genomic DNA revealed a polymorphism linked to the CD38 gene. PMID- 2319136 TI - HPLC immunoaffinity purification of rabies virus glycoprotein using immobilized antipeptide antibodies. AB - It has been reported that the acetylcholine receptor may be used by the rabies virus to concentrate at sites in proximal to peripheral nerves. It has also been reported that the binding site for the receptor is located within the 190-203 region of the virus glycoprotein on the basis of its structural homology with the toxic center of snake neurotoxins, which are well known cholinergic ligands. We prepared monoclonal antibodies against the synthetic tetradecapeptide having the same sequence as the putative binding site of the rabies virus. One of three antibodies (clone 2PV 36-74) was able to recognize both the whole virus and its peplomeric glycoprotein and could bind acetylcholine. It was also able to inhibit the binding both of alpha-bungarotoxin and rabies virus glycoprotein to the acetylcholine receptor. We have covalently bound 2PV 36-74 to an HPLC affinity column and utilized it for specific purification of rabies virus glycoprotein. The immunoaffinity chromatographic method we describe is very sensitive and highly specific. Moreover this procedure does not denature the sample and is vary rapid and efficient. PMID- 2319137 TI - Immobilization of immunoglobulins on ethanol-treated ABS beads for radioimmunoassays. PMID- 2319138 TI - A simple method for measuring patient anti-globulin responses against isotypic or idiotypic determinants. AB - A simple inhibition of capture enzyme-linked immunosorbent assay (IOC-ELISA) was developed which permitted the independent measurement of anti-idiotypic and anti isotypic antiglobulins in serum samples from patients receiving therapeutic monoclonal antibodies. PMID- 2319139 TI - Measurement of association constants in ELISA. Reactions between solid-phase antibody and fluid-phase biotinylated antigen. AB - An ELISA procedure which utilized an avidin-peroxidase amplification reaction to detect and quantify the amount of fluid-phase biotinylated antigen bound to solid phase antibody was developed to determine antibody association constants. The methodology required is uncomplicated, avoids the use of radioisotopes, and is theoretically amenable for use with any protein which can be biotinylated, and any receptor protein which can be immobilized on plastic wells. A plot of known immobilized biotinylated antigen concentrations, which ranged from approximately 100 ng/ml to 1000 ng/ml, versus avidin-peroxidase conjugate product formation, was used to establish a standard curve from which the amount of antibody associated antigen in binding assays could be determined. Antibody association constants obtained with this method ranged from 10(5) to 10(9) M-1. PMID- 2319140 TI - Culture of human tumor infiltrating lymphocytes in hollow fiber bioreactors. AB - Human tumor infiltrating lymphocytes (TIL) from metastatic melanoma of six patients were grown using a new hollow fiber bioreactor system. After inoculating 0.35-10 X 10(8) TIL into the extra-fiber space (EFS), each Cellmax bioreactor was perfused with AIM-V medium, supplemented with rIL-2. The cells subsequently expanded 124-1170-fold to yield 1.5-5.4 X 10(10) TIL over a 14-32 day period. TIL were flushed from the EFS using 200 ml medium and possessed an average viability = 91%. The phenotype and the autologous tumor cell lytic capacity of these TIL were similar to those of TIL grown in the currently used gas-permeable culture bags. Tissue culture media use averaged 4.3 liters/10(10) TIL harvested. The TIL of one patient were re-expanded twice from cells remaining within the same bioreactor after harvest suggesting that one bioreactor cartridge could be used for repetitive, periodic studies. An estimated 80% decrease in technical time expended and in incubator space requirements were realized using this methodology. Cell culture on hollow fibers appears to be a useful method for producing large quantities of primary human lymphocytes for experimental, and perhaps, therapeutic needs. PMID- 2319141 TI - Increased yield of antibody-producing murine spleen cell hybridomas from fusions cultured in medium supplemented with mouse serum. AB - The number of monoclonal antibody-producing murine hybridomas were increased 7-10 fold in three separate fusions when supplementing the FBS-containing, or serum free, growth factor-containing, culture medium with 5% normal mouse serum. The beneficial effect was seen in fusions of A/J and 129GIX+ spleen cells, from primary and secondary responses, and when using SP2/0 or P3X63Ag8U.1 as the fusion partner. PMID- 2319142 TI - Haptenated nylon-coated polystyrene plates as a solid phase for ELISA. AB - An ELISA system, based on the novel use of a hapten-nylon conjugate as solid phase coating antigen, has been applied in the screening of hybridoma cultures for anti-hapten monoclonal antibodies directed against the herbicide atrazine and its derivatives. Conjugation of a 2-aminocaproic acid derivative of atrazine with DCC to polyamide (Nylon 6) gave haptenated nylon which was soluble in aqueous cresol-ethanol mixtures and adsorbed efficiently on polystyrene microtitre plates. Reproducible ELISA results were obtained with culture supernatants of hybridomas derived from spleen cells of mice that had been immunized with atrazine-bovine serum albumin conjugates. Satisfactory results were also obtained with a water soluble peptide conjugated to nylon for use as a coating antigen in an ELISA. Plates coated with hapten-nylon as antigen have the added advantage that they can be stored at room temperature for at least 6 months without loss of activity. Nylon therefore appears to have general applicability as a carrier for both non-polar and polar haptens in the preparation and use of coating antigens. PMID- 2319143 TI - The use of primed cytotoxic T lymphocytes as a highly sensitive and accurate method for the detection of MHC disparate allogeneic cells. AB - The present studies have investigated the use of primed cytotoxic T cells (CTL) for the purpose of detecting the presence of an MHC disparate allogeneic cell population. The findings indicate that restimulation of primed CTL in the presence of activated T cell supernatants is an extremely sensitive method capable of detecting one allogeneic cell within a population containing 10,000 total cells (0.01%). In addition, this primed lymphocyte cytotoxicity assay (PLCA) was shown to be at least as accurate as flow cytometric analysis in determination of low numbers and percentages of allogeneic cells within the cell population being examined. Furthermore, the nature of the allogeneic mononuclear population did not influence the sensitivity or accuracy of this method. To examine this method's applicability for the detection of chimeric populations in vivo, spleen and thymic tissue from neonatally tolerized animals were examined by PLCA analysis. Allogeneic cells were readily detected in 100% of individual host spleen and thymuses tested. In total, the results showed that the PLCA is a highly reproducible and accurate method for the detection of extremely low numbers of allogeneic cells. This approach should be useful to monitor the presence of foreign cells in experimental and clinical situations in which individuals are exposed to allogeneic cell populations. PMID- 2319144 TI - Heterosexual contact as a major route for transmission of acute hepatitis B among adults. AB - Possible routes for transmission of acute hepatitis B were studied retrospectively in 78 consecutive adult patients seen at the Department of Infectious Diseases, Roslagstull Hospital in Stockholm. Sexual transmission was found to be a major route of transmission, being more common than intravenous drug abuse. A single possible route of transmission was found in 66/78 (84%) patients. Eleven of the 78 patients (14%) had two possible routes, sexual contact being one. Overall sexual contact possibly accounted for 53% of all cases of hepatitis B, homosexual contact being responsible for only 10%. Cases reported earlier as being of unknown origin or associated with a recent visit abroad or to be 'social contact cases' are probably most often due to heterosexual transmission. Seven patients (9%) were heterosexually infected by persons who had been recently receiving medical care for hepatitis B. Seven sexually transmitted cases of acute clinical hepatitis B secondary to the patients studied were seen also. These findings show that sexual transmission, mainly heterosexual, is a major route for transmission of hepatitis B in a western society. They also emphasise the importance of taking an adequate sexual history as a prerequisite for providing effective prophylaxis for sexual partners of patients with acute hepatitis B. PMID- 2319145 TI - Metronidazole resistant Bacteroides fragilis infection of a prosthetic hip joint. AB - A case of infection involving a prosthetic joint in a patient with adult Still's Disease is described. The causative organism was a strain of Bacteroides fragilis which was resistant to metronidazole. The rarity of this occurrence is emphasised. Diagnostic difficulties which arose are described and the problems encountered with therapy discussed. PMID- 2319146 TI - Haemophilus influenzae and H. parainfluenzae as urinary pathogens. AB - Two cases are described, one of Haemophilus influenzae urinary infection in a female with no past history of urinary tract infection (UTI) and the other of Haemophilus parainfluenzae infection in a male with a renal calculus. Haemophilus spp. are rare urinary pathogens and these cases are even more unusual because H. influenzae UTI has almost always previously been found in either children or adult males, while H. parainfluenzae UTI has only been reported once before. PMID- 2319147 TI - Reactive arthritis complicating group G streptococcal septicaemia. AB - We describe a case of group G streptococcal septicaemia complicated by sterile polyarthritis and pericarditis. We suggest that this organism may cause a 'reactive arthritis' type of illness, and that this is in keeping with known properties of the organism. We note that our patient's clinical features fit the modified Jones criteria for the diagnosis of rheumatic fever. PMID- 2319148 TI - Q fever encephalitis. AB - Encephalitis is a rare but documented complication of acute Q fever. We report here the case of a 48-year-old lady who presented with an acute illness characterised by influenza-like symptoms, pneumonia and neurological disturbance but in whom the serology was suggestive of chronic rather than acute Q fever. PMID- 2319149 TI - Acute viral hepatitis B, reported to the Public Health Laboratory service. PMID- 2319150 TI - Aeromonas associated diarrhoea in an otherwise healthy 70-year-old man. PMID- 2319151 TI - Campylobacter fetus infections in two patients with AIDS. PMID- 2319152 TI - Idiosyncratic reaction to nebulised ribavirin. PMID- 2319153 TI - Elimination half-life of amphotericin B. PMID- 2319154 TI - Transfusion acquired hepatitis A in a patient with B thalassaemia major. PMID- 2319155 TI - Staphylococcal enterotoxins A and C causing toxic shock syndrome. PMID- 2319156 TI - Trichosporon beigelii peritonitis in continuous ambulatory peritoneal dialysis. PMID- 2319157 TI - Fatal visceral disease caused by a dermotropic Leishmania in a patient with human immunodeficiency virus infection. PMID- 2319158 TI - Toxic shock syndrome and enterotoxin C. PMID- 2319160 TI - 'Exotic' parasitic infections: recent progress in diagnosis and management. PMID- 2319159 TI - Aetiology of the 'urethral syndrome'. PMID- 2319161 TI - In vitro isolation of Entomophthora muscae (Entomophthorales: Entomophthoraceae) from infected seed corn maggot Delia platura (Diptera: Anthomyiidae). PMID- 2319162 TI - Dimorphic development of Amblyospora sp. (Microspora: Amblyosporidae) in Culex salinarius gynandromorphs. PMID- 2319163 TI - Occurrence of two pathotypes in Bacillus thuringiensis subsp. fukuokaensis (flagellar serotype 3a:3d:3e). PMID- 2319164 TI - Association between respiratory syncytial virus outbreaks and lower respiratory tract deaths of infants and young children. AB - The temporal patterns of respiratory virus isolations from 10 laboratories in the USA were compared with that of deaths of children less than 5 years old from July 1975 through June 1984. Isolations of respiratory syncytial virus (RSV) occurred as yearly winter outbreaks; parainfluenza virus 1 and 2 isolations occurred as well-defined outbreaks every other year in the autumn; parainfluenza virus 3 isolations occurred throughout the year with periodic, increased isolations suggestive of outbreaks; and influenza virus isolations (A, B, or A plus B) occurred as yearly winter outbreaks. After data were controlled for seasonal patterns, RSV isolations were strongly correlated with the winter peaks in lower respiratory tract illness (LRI) deaths of infants 1-11 months old; influenza virus isolations were correlated with the winter peak in LRI deaths of children 24-59 months old. The parainfluenza viruses were not correlated with respiratory deaths. This study supports the idea that RSV is a major contributor to winter peaks in LRI deaths of children 1-11 months old. PMID- 2319165 TI - An outbreak of hepatitis A among cancer patients treated with interleukin-2 and lymphokine-activated killer cells. AB - An outbreak of hepatitis A virus (HAV) infection occurred among cancer patients treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells between July and September 1986 at six different clinical centers. Among 85 patients tested serologically for recent HAV infection, 22 (39%) of 56 susceptible patients developed acute HAV infection. Only exposure to LAK cells cultured in medium containing human serum from two specific manufactured pools was associated with HAV infection. Attack rates were 85% among patients exposed to pool X, 62% in patients exposed to pool Y, and 50% in those exposed to both pools, compared with none among the 24 susceptible persons exposed to other serum pools (P less than .001). The serum used in production of LAK cell medium was obtained from multiple paid donors. Twenty persons donated plasma to both serum pools X and Y. Although none of 12 donors tested had evidence of recent HAV infection, it is likely that an asymptomatic plasma donor viremic for HAV contaminated both serum pools and the LAK cell medium made from it. PMID- 2319167 TI - Does naturally acquired IgG antibody to cell wall polysaccharide protect human subjects against pneumococcal infection? AB - Antibody to the non-serotype-specific cell wall polysaccharide (CWPS) of Streptococcus pneumoniae has been said to confer a degree of non-serotype specific protection against pneumococcal infection. The hypothesis underlying the present study was that if this antibody is protective, relatively higher levels are likely to be detected in patients who are colonized by pneumococci but do not have infection, those who have febrile bronchitis but do not have pneumonia, and those who have pneumococcal pneumonia but are not bacteremic. Mean IgG reactive with CWPS by ELISA in 15 healthy young adults was 43.9 micrograms/ml and in 126 randomly selected hospital patients of all ages was 41.9 micrograms/ml. In subjects with chronic bronchitis with or without known pneumococcal carriage, mean anti-CWPS IgG was 87.7 micrograms/ml. In three groups of patients (3 with acute purulent tracheobronchitis, 13 with nonbacteremic pneumococcal pneumonia, and 14 with S. pneumoniae bacteremia) at the time of admission, mean antibody levels were essentially identical, 104.9-110.1 micrograms/ml. The data suggest that naturally present anti-CWPS IgG does not protect against the evolution of acute pneumococcal infection from colonization to acute purulent bronchitis, from bronchitis to pneumonia, or from pneumonia to bacteremia. PMID- 2319166 TI - Pneumococcal polysaccharide vaccine in young adults and older bronchitics: determination of IgG responses by ELISA and the effect of adsorption of serum with non-type-specific cell wall polysaccharide. AB - Available pneumococcal vaccines provide only limited protection for certain at risk populations. Fifteen healthy young adults and 11 older chronic bronchitics received 23-valent pneumococcal vaccine. ELISA showed that IgG reactive with capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 8, 14, and 19F increased after vaccination. Bronchitics exhibited lesser responses for four of these serotypes, although differences between the groups were significant only for serotype 3. Adsorption of postvaccination sera with pneumococcal cell wall polysaccharide significantly reduced mean antibody levels in both groups and lowered the proportion of sera that demonstrated type-specific antibody responses. Reactive IgG was largely restricted to the IgG2 subclass. Pneumococcal vaccine may provide suboptimal protection of older adults because antibody responses to some capsular polysaccharides are lower in elderly bronchitics than in healthy young adults. A substantial proportion of measured antibody reflects IgG reactive with cell wall polysaccharides rather than with type-specific, capsular constituents, suggesting that antibody responses in subjects of all ages deserve reappraisal. PMID- 2319168 TI - Administration of recombinant interleukin-2 reduces the local parasite load of patients with disseminated cutaneous leishmaniasis. AB - Three patients with disseminated cutaneous leishmaniasis received three intranodular injections of 10 micrograms of recombinant interleukin 2 (rIL-2) at 48-h intervals. After 7 and 14 days, 4-mm punch biopsies were taken of control and injected nodules and processed for histology, electron microscopy, immunocytochemistry, and parasite culture. Control sites exhibited loose infiltrates of parasitized macrophages and T cells predominantly of the CD8+ phenotype. Amastigotes were present in large numbers and were found distributed within tightly apposed endosomes and larger vacuoles. After the administration of rIL-2, there was a prominent influx of T cells, predominantly of the CD4+ phenotype, and an increased number of plasma cells. At 7 days, leishmanial amastigotes were present in either the same or somewhat reduced numbers but predominantly within large, lucent vacuoles. By 14 days the number of amastigotes was strikingly lower. Lymphokine-treated skin sites became sterile in two patients, as evaluated by parasite culture after rIL-2 injection. The results suggest that the local administration of rIL-2 induces a beneficial enhancement of the cellular immunity with a consequent disposal of parasites in the cutaneous site. PMID- 2319169 TI - Respiratory syncytial virus in a community population: circulation of subgroups A and B since 1965. AB - Respiratory syncytial viruses were isolated from residents of Tecumseh, MI, with illnesses of all severities during the periods 1965-1971 and 1976-1981. These isolates were grouped using one monoclonal antibody specific for each subgroup. All were identified as either subgroup A or B. Subgroup A predominated in most years. No differences in age distribution or illness characteristics could be found between the subgroups. This study demonstrated that the currently recognized subgroups have been present in a single community since 1965, and their behavior in the past is similar to that currently described. PMID- 2319170 TI - Persistent enterovirus infection in culture-negative meningoencephalitis: demonstration by enzymatic RNA amplification. AB - Chronic meningoencephalitis due to enterovirus infection can occur in patients with antibody deficiencies. A modified polymerase chain reaction technique demonstrated persistent echovirus 11 infection in such a patient, despite negative routine viral cultures and negative routine nucleic acid hybridization. Although the sequence of echovirus 11 has not yet been determined, genomic conservation among the enteroviruses is significant, permitting detection of echovirus 11 with a primer pair and probe derived from enterovirus serotypes that have been fully sequenced. This study provides the first definitive evidence for the persistence of enterovirus infection with negative viral cultures. PMID- 2319171 TI - Intermittent antimicrobial prophylaxis for recurrent acute otitis media. PMID- 2319172 TI - Candida antigen latex test. PMID- 2319174 TI - Borrelia burgdorferi and Ixodes dammini prevalent in the greater Philadelphia area. PMID- 2319173 TI - Detection of human immunodeficiency virus type 1 (HIV-1) in genital ulcer exudate of HIV-1-infected men by culture and gene amplification. PMID- 2319175 TI - Treatment of prosthetic valve endocarditis due to methicillin-resistant Staphylococcus aureus with minocycline. PMID- 2319176 TI - Binding of bone sialoprotein to Staphylococcus epidermidis isolated from a patient with chronic recurrent multifocal osteomyelitis. PMID- 2319177 TI - Soft-tissue infection caused by Edwardsiella tarda and Aeromonas hydrophila. PMID- 2319178 TI - [Proteoglycan-like antigens associated with subsets of neurons]. PMID- 2319179 TI - Influence of social perceptions of leprosy and leprosy patients on public health programs. PMID- 2319180 TI - Cutaneous lymphoma masquerading as lepromatous leprosy. PMID- 2319181 TI - Relapse or late reversal reaction? PMID- 2319182 TI - Blister calendar packs for dapsone monotherapy. PMID- 2319183 TI - An attempt to demonstrate antinerve antibodies in leprosy sera using rabbit nerve as an antigen. PMID- 2319184 TI - Twenty-fourth Joint Leprosy Research Conference. San Diego, California, U.S.A., 23-25 August 1989. Abstracts. PMID- 2319185 TI - Relapses in paucibacillary leprosy after MDT--a clinical study. AB - A study was undertaken in a field-based project to assess the incidence and clinical profile of relapses occurring in paucibacillary leprosy patients after adequate doses of multidrug therapy (MDT). Of the 1509 paucibacillary patients who had received not less than 6 doses of MDT (WHO regimen), 85 relapsed; a relapse rate of 5.63% (17.5/1000 person years at risk). These relapses included 12 cases with features of reversal reaction. Seventy-nine percent of the patients relapsed with skin lesions. The relapse rate was higher in borderline cases and in those with more lesions, and it was lower in those who had received dapsone for at least 6 months after cessation of MDT. Seventy-four percent of the relapses were detected between 7 and 24 months of follow up. We feel that uniform clinical criteria should be formulated for the diagnosis of relapse. Individualization of therapy, rather than adhering to a fixed duration of MDT, would be likely to achieve satisfactory cure rates and fewer relapses. PMID- 2319186 TI - Activation of complement by circulating immune complexes isolated from leprosy patients. AB - Circulating immune complexes isolated from different types of leprosy sera as polyethylene glycol (PEG) precipitates were found to be efficient activators of the alternative pathway of complement. PEG precipitates from BL/LL leprosy patients and those with erythema nodosum leprosum were found to activate both the classical pathway and the alternative pathway of complement efficiently, while PEG precipitates from TT/BT leprosy patients and borderline tuberculoid patients in reaction were found to active the alternative pathway of complement but not the classical pathway. No significant differences were observed between the PEG precipitates from reactional and nonreactional TT/BT and BL/LL patients in their complement activating ability. PMID- 2319187 TI - Intraocular pressure and iris denervation in Hansen's disease. AB - We retrospectively analyzed 255 Hansen's disease patients and found low intraocular pressure (less than 7 mm Hg) in 12% of them. We showed a correlation between low intraocular pressure and avascular keratitis and iritis. We also found that patients with low intraocular pressures had abnormally large postural changes in intraocular pressure. We speculate that abnormalities in the autonomic innervation of the anterior segment of the eye may be related to the intraocular pressure abnormalities. Further investigations along this line may increase our understanding not only of the pathophysiology of Hansen's disease but also of the mechanisms regulating homeostasis of intraocular pressure. PMID- 2319188 TI - Variation in immunogenicity of mycobacteria: role of antigen-presenting cells. AB - The antigen-presenting efficiency of peritoneal cells and irradiated spleen cells was compared using Mycobacterium tuberculosis- and M. vaccae-primed T cells and corresponding sonicates as antigens in an in vitro lymphocyte transformation test. The presentation efficiency of irradiated spleen cells was reasonably good for both antigens. However, with peritoneal cells as the antigen-presenting cells, the proliferative response against only M. tuberculosis sonicate was good. Proliferation of M. vaccae-primed T cells was very poor when the antigen was presented by peritoneal cells. Poly I:poly C treatment of mice prior to harvesting the peritoneal cells resulted in distinct improvement in their efficiency to present M. vaccae sonicate; maximal proliferative response was obtained with peritoneal cells from mice receiving two and three doses of poly I:poly C 24 hr apart. Even paraformaldehyde-fixed peritoneal cells from poly I:poly C-treated mice gave an efficient M. vaccae-specific stimulation to primed T cells. Based on these data, it was concluded that failure of mice to respond to M. vaccae by intraperitoneal immunization is the result of the poor efficiency of presentation of M. vaccae antigen. PMID- 2319189 TI - The 1989 Journal--a continuing perspective. PMID- 2319190 TI - Naviculo-cuneiform coalition--report of three cases. AB - Naviculo-cuneiform coalition is a very rare condition and has only been reported by Lusby and Miki. We hereby describe three cases of this condition. The chief complaint was mild pain in the midfoot region especially after physical activity. There were no detectable deformities such as calcaneo-valgus, flatfoot or peroneal spastic foot, moreover the range of motion of the subtalar joint appeared to be normal. Conventional tomography confirmed coalition in two out of our three cases. 99mTc-MDP bone scintigraphy may be useful as a screening procedure. In past the pain associated with tarsal coalition was considered to result from the decreased range of motion in the fused joint due to ossification. However, our study have indicated that pain appeared to originate from the weakness of the cartilagenous bridges relative to the weight-bearing force over the naviculo-cuneiform joint. PMID- 2319191 TI - Trabecular mineral contents of lumbar vertebra in patients with osteoporosis. AB - The trabecular mineral contents (TMCs) of the third lumbar vertebra in normal subjects and patients with spinal osteoporosis and with femoral neck fracture were measured by quantitative computed tomography (QCT) using a reference phantom. The present paper describes these results. The TMCs in patients with spinal osteoporosis and with femoral neck fracture were significantly lower than those in normal subjects. When evaluated in terms of the ratio to the mean trabecular mineral content (mTMC) in normal subjects of the same decade groups, it was assumed that there should be a threshold value of vertebral compression fracture, and that value was approximately 50% of the mTMC in normal subjects. A correlation was noted between the data of the QCT method and those of the microdensitometric method in the groups with vertebral compression fracture and with femoral neck fracture, but not in the group without vertebral fracture. PMID- 2319192 TI - [Clinical and experimental studies on ascending cauda equina action potential (A CEAP) in lumbar lesion with reference to positivisation]. AB - The phenomenon of positivisation in ascending cauda equina action potential (A CEAP) was evaluated in 114 patients with lumbosacral lesions. These patients were divided into two groups, i.e., non-positivisation and positivisation group. In the former, positive wave ratio was highest at the L5/S upon stimulating the peroneal nerve. In the latter, the positivisation at the L4/5 upon stimulating the peroneal nerve spread not only to the cranial level but also to the caudal L5/S level. Based on these experimental results, the factors causing positivisation in the L5/S level without lesion were: 1) curving effect of the L5 nerve root, 2) augmentation of current density within the spinal canal and 3) the amount of individual impulses propagating along the L5 and S1 root. PMID- 2319193 TI - [Study on the strength and microcleanliness of the stem of the total hip prostheses]. AB - Using 8 types of total hip prosthetic stems that are presently the most commonly used in clinical applications, we conducted a mechanical and metallurgical study based on measurements of strength and microcleanliness. The Muller, Kyocera Bioceram 4M type and the Thackray Charnley proved to be excellent in terms of strength, whereas the Muller and Kyocera Bioceram 4M type yielded superior results for microcleanliness. The strength and microcleanliness of the casts were of a lower grades, allowing the wroughts to be superior to the former. Vacuum melted stems gave particularly favorable results. Even those stems which had been made with the same mold or of the same metallic material varied in terms of strength and microcleanliness depending upon the manufacturing processes. There were notable correlations among microcleanliness, O2 content and strength, and improvements in metallic materials and manufacturing processes will enable us to minimize nonmetallic inclusions and O2 contents and thus increase the strength and microcleanliness as well. PMID- 2319194 TI - [Electrophysiological diagnosis in ulnar nerve entrapment at elbow]. AB - Using "inching technique" we recorded antidromic sensory nerve action potentials from the little finger and compound muscle action potentials from the abductor digiti minimi, first dorsal interosseous and flexor carpi ulnaris muscles in 30 entrapped ulnar nerves. In cubital tunnel syndrome, localized conduction delay occurred most commonly at a point 2 to 4 cm distal to the medial epicondyle. In other ulnar neuropathies, with the exception of cubitus valgus deformity, conduction block or delay was noted at a site just distal to the medial epicondyle. These conduction abnormalities were most commonly observed in the abductor digiti minimi and first dorsal interosseous. In contrast, conduction abnormality in tardy palsy secondary to the valgus deformity reflected mainly in the flexor carpi ulnaris. This method provides useful information in diagnosing the early involvement and precise localization of nerve entrapment, and differentiation of cubital tunnel syndrome from other ulnar nerve entrapment. PMID- 2319195 TI - [The effect of CdCl2 and ZnCl2 on Dunn osteosarcoma]. AB - Three murine sarcoma cells (Dunn osteosarcoma, Gunma clone-4, Sarcoma 1509a) were cultured for four days at various concentrations of CdCl2 or ZnCl2 and assayed for their viability. Dunn osteosarcoma was more sensitive to CdCl2 and less sensitive to ZnCl2 than the others. CdCl2 and ZnCl2 were weekly administered to C3H/He mice intraperitoneally from three days after the inoculation of Dunn osteosarcoma. The size of the tumors was measured twice a week for five weeks. CdCl2 suppressed the growth of the tumor, whereas ZnCl2 did not. These results suggest that CdCl2 has antitumor activity, especially against osteosarcoma. PMID- 2319196 TI - The effect of oxygen tension on collagen synthesis and calcium uptake in newborn rats' calvaria in vitro. AB - Using newborn rat calvaria, we determined the effects of oxygen tension on bone cell metabolism in vitro. Halved calvaria were incubated in medium either in air or after flushing nitrogen or oxygen and studied for collagen synthesis, calcium uptake, and DNA content. The percentages of DNA content, radioactive proline count in mg of bone tissue, and radioactive proline count combined with counts of medium and bone tissue in the nitrogen-exposed group were less than those of their pair-matched controls. Percent calcium counts per DNA and calcium uptake per mg of tissue were greater in the nitrogen-exposed group than in the pair matched controls. In contrast, no difference was found in any measurements in the oxygen-exposed group compared with controls. It is concluded that collagen synthesis, in contrast to proline uptake, is not affected by low oxygen, whereas calcium uptake is greatly enhanced. Furthermore, low oxygen tension exerts a greater effect on bone cell metabolism than does the hyperoxic condition. PMID- 2319197 TI - [Beneficial effect of a selective TXA2 synthetase inhibitor, OKY-046, both on thromboxane B2 production and vascular damage after spinal cord injury in rat spinal cord]. AB - Thromboxane A2 (TXA2) is an eicosanoid with potent platelet aggregation and vasoconstricting activity, while prostaglandin I2 (PGI2) antagonizes its activity. But these eicosanoids are so labile that the stable degradation products, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), are determined in biological materials. In a rat spinal cord compression injury model, a production of TXB2 reached a peak (133.6 +/- 13.8 pmol/g cord) 5 minutes after compression injury, while that of 6-keto-PGF1 alpha slightly increased (26.2 +/- 11.7 pmol/g cord). And the magnitude of the increase in TXB2 and the extent of post-traumatic vascular damage as determined by fluorescein uptake were both dependent on the degree of spinal cord compression injury. We also studied the effect of a selective TXA2 synthetase inhibitor, OKY-046 [E)-3 [4-(1-imidazolylmethyl)phenyl]-2-propenoic acid), both on TXB2 production in the injured spinal cord and post-traumatic vascular damage. When OKY-046 was administered intravenously 10 minutes prior to compression injury at a dose of 500 micrograms/kg body weight, the increased production of TXB2 was inhibited by about 80% and uptake of sodium fluorescein was reduced by a maximum of 40%. When the compression injury was induced before OKY-046 was administered, the inhibitory effect of OKY-046 on TXB2 production decreased depending on the duration before administration. In contrast, the 6-keto-PGF1 alpha level was not affected in the presence of OKY-046. PMID- 2319199 TI - [63d annual meeting of the Japanese Orthopedic Association. Nagoya, 12-15 April 1990. Abstracts]. PMID- 2319198 TI - A harvesting method of monocytes/macrophages derived from bone marrow and their characteristics--special reference to the effect of 1,25-dihydroxyvitamin D3 on monocytes/macrophages. AB - We have investigated the relationship between monocytes/macrophages and bone metabolism with the in vitro study. In the present study monocytes/macrophages derived from rat bone marrow were harvested and their phenotype was examined. Collected cells exhibited many characteristics of monocytes/macrophages at various points. In addition, 1,25-dihydroxyvitamin D3(D3), one of the osteotropic hormones was found to alter the activities of acid phosphatase (AcPase) and lysozyme in the media and also stimulate alkaline phosphatase (AlPase) positive cells to increase in number. PMID- 2319200 TI - Management of pediatric mandibular fractures. AB - The incidence of mandibular fractures is rare in the pediatric population when compared to adults. Although the basic principles for management are the same as for the adult, certain anatomical features of the pediatric mandible warrant special attention. Problems such as mixed dentition, unerupted teeth, and ongoing growth in the mandible require careful diagnosis and planning in deciding on the proper treatment. PMID- 2319201 TI - Pediatric intraosseous infusion. AB - Venous access in the infant and child is always challenging. The hypotensive child who is deteriorating needs rapid volume expansion and medications. Vascular collapse and previous venous cut-downs can preclude easy cannulation of vessels. Intraosseous infusion of fluids and drugs can be readily performed. The technique is easily mastered and there are few complications. PMID- 2319202 TI - Tuberous sclerosis. AB - The strong relationship between tuberous sclerosis, cardiac rhabdomyoma, and angiomyolipoma of the kidney is well illustrated in this family case study. PMID- 2319203 TI - ECG of the month. A regional event. Extensive anterior wall myocardial infarction. PMID- 2319204 TI - Oxidative metabolism in the alveolar macrophage: analysis by flow cytometry. AB - We evaluated the reagents dichlorofluorescin (DCFH) and hydroethidine (HE) for use in flow cytometric analysis of the respiratory burst of alveolar macrophages and monocytes. DCFH and HE are non-fluorescent precursors which can be oxidized intracellularly to the fluorescent compounds dichlorofluorescein and ethidium. Alveolar macrophages (AMs) loaded with either DCFH or HE were analyzed after phorbol myristate acetate (PMA) stimulation. The results, expressed as fmol/cell oxidation product (DCF or ethidium) after fluorometric standardization of the flow cytometer, show that both DCFH (273 +/- 48, mean increase over control +/- SE, fmol/cell, N = 9) and HE (416 +/- 54, N = 11) detected the substantial respiratory burst of hamster AMs. Similar results were obtained with normal human AMs. By using multiparameter analyses, the oxidative response of AMs ingesting opsonized fluorescent latex beads was measured in subpopulations ingesting increasing numbers of particles. A graded increase in oxidation of both DCFH and HE was found in response to increasing phagocytosis. Ingestion of fluoresceinated staphylyococcal bacteria caused similar changes in HE-loaded AMs. Inhibition of respiration with antimycin showed that approximately 95% of the increased oxidative metabolism of hamster AMs ingesting opsonized beads or bacteria was mitochondrial. The remaining 5% (10-40 fmol/cell) is membrane-derived oxidative activity quantitatively similar to that measured in assays of extracellular release of H2O2. Monocytes loaded with either DCFH or HE showed substantial increases in fluorescence after PMA stimulation (mean % increase over control +/- SE at 30 min: 464 +/- 104, DCFH, 505 +/- 156, HE). While DCHF is known to measure H2O2, HE is less well characterized. Exposure of cells to an extracellular source of both superoxide anion (O2-) and H2O2, xanthine oxidase-xanthine, resulted in marked oxidation of intracellular HE. Addition of both superoxide dismutase and catalase blocked this oxidation, indicating that HE can detect both O2- and H2O2. These agents can be useful probes for precise analysis of oxidative metabolism during phagocytosis in AMs and other mononuclear phagocytes. PMID- 2319205 TI - Interaction of immune and connective tissue cells: I. The effect of lymphokines and monokines on fibroblast growth. AB - In order to determine if mononuclear cells may be secreting factors capable of modulating fibroblast growth, the in vitro proliferative response of fibroblasts to cytokines known to be secreted by mononuclear cells was measured, using both growth arrested and proliferating cells. Of the cytokines tested, which included interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-6 (IL-6), interferon-alpha (IFN-alpha), interferon-gamma (IFN gamma), transforming growth factor-alpha (TGF-alpha), transforming growth factor beta (TGF-beta), platelet derived growth factor (PDGF), and tumor necrosis factor alpha (TNF-alpha), only TNF-alpha and PDGF had demonstrable growth factor activity. Neither IL-1 alpha nor beta showed any true growth factor activity but were able to enhance the replication of already proliferating cells. No inhibition of proliferation was noted by any of the cytokines with the exception of TNF-alpha and TGF-beta. TNF-alpha in doses greater than 500 ng/ml caused fibroblast death, probably by a prostaglandin related mechanism as fibroblasts remained viable, although non proliferative, when assayed in the presence of indomethacin, a known inhibitor of prostaglandin E2 (PGE2) synthesis. TGF-beta was inhibitory to proliferation at doses greater than 100 ng/ml, while fibroblasts remained viable. This effect was not influenced by indomethacin and hence is unlikely to be PGE2 related. PMID- 2319206 TI - Immunologic consequences of taurine deficiency in cats. AB - Our results show that a lack of taurine in the diet of cats results in a significant leukopenia, a shift in the percentage of polymorphonuclear and mononuclear leukocytes, an increase in the absolute count of mononuclear leukocytes, and a change in the sedimentation characteristics of white cells. Functional studies of polymorphonuclear cells isolated from cats fed taurine-free diets show a significant decrease in the respiratory burst as measured by chemiluminescence as well as a decrease in phagocytosis of Staphylococcus epidermis compared to cats fed the same diet containing taurine. In addition, serum gamma globulin in cats fed taurine-free diets was significantly increased compared to taurine-supplemented cats, indicating that other immune cells may be affected by taurine deficiency. Histological examination of lymph nodes and spleen revealed regression of follicular centers with depletion of reticular cells, mature and immature lymphocytes (B cell areas), as well as mild extravascular hemolysis. These results indicate that there are profound immunologic consequences in cats with prolonged taurine deficiency. PMID- 2319207 TI - Influenza A virus alters structural and biochemical functions of the neutrophil cytoskeleton. AB - Influenza A virus (IAV) has previously been shown to alter chemotactic, oxidative, and secretory functions of polymorphonuclear leukocytes (PMNL). Because of the role of cytoskeletal proteins in these processes, studies were carried out to determine if IAV altered the PMNL cytoskeleton. PMNL were incubated with buffer of IAV, stimulated with f-met-leu-phe (FMLP), fixed and stained with NBD-phallacidin (NBD-Ph) and studied by flow cytometry. Mean F-actin fluorescence was increased 18% in virus treated cells pre-FMLP stimulation and 13% 5 and 10 min post-FMLP (P less than .03); no significant difference in F actin fluorescence was noted in virus treated PMNL 15-30 s post-FMLP compared to control cells. PMNL exposed to the same conditions were solubilized and actin content was determined following SDS-PAGE of triton insoluble precipitates. Increased actin was recovered from virus treated compared to buffer treated cells before and after FMLP stimulation in the 8,000g precipitates (P less than .001). Immunofluorescent microscopy studies of F-actin distribution were done in PMNL stained with NBD-Ph following FMLP stimulation for 10 min. These studies showed an increased lamellipod F-actin/uropod F-actin ratio in PMNL pre-incubated with IAV compared to controls (4.6 vs. 1.0; P less than .025). Phosphorylation of specific cytoskeletal proteins was examined after immunoprecipitation. IAV alone altered phosphorylation of both vimentin and vinculin, and in stimulated PMNL virus led to decreased phosphorylation of vimentin and vinculin. These data show distributional and biochemical effects of IAV on PMNL cytoskeletal proteins, indicating additional targets for IAV interference in the PMNL signal transduction-function process. PMID- 2319208 TI - Physiologic oxygen tensions limit oxidant-mediated killing of schistosome eggs by inflammatory cells and isolated granulomas. AB - Explanted hepatic granulomas, eosinophils obtained from the peritoneal cavity of schistosome-infected mice, schistosome egg granuloma macrophages, alveolar macrophages, and activated peritoneal macrophages obtained from Listeria-infected mice were miracidicidal when cultured at 21% oxygen. This activity was markedly attenuated at physiologic oxygen concentrations (1-15%). Catalase and superoxide dismutase blocked the miracidicidal activity of inflammatory cells but did not prevent granuloma-mediated egg killing. However, the biomimetic superoxide dismutase, copper (II) [diisopropyl salicylate]2, inhibited granuloma-mediated egg killing in a dose-dependent, apparently nontoxic manner. Thioglycollate elicited macrophages did not kill schistosome egg miracidia even when cultured in 21% oxygen, unless pretreated with lipopolysaccharide. Isolated schistosome eggs initiated an oxidative burst in macrophages, as measured by superoxide anion production. This burst was suppressed at reduced oxygen concentrations. Thus schistosome egg miracidia can be killed nonspecifically by macrophages through the release of cytotoxic reactive oxygen intermediates triggered by the egg. This activity is not supported by the oxygen concentrations found in most tissues, with the possible exception of the lung. Schistosoma mansoni eggs, injected intraveneously and lodged in the pulmonary vasculature of mice, were killed rapidly, with a half life of 3.5 days. Eggs, injected into the mesenteric veins and lodged in the liver, remained fully viable for several weeks. The data suggest that the high oxygen tension of the lung allows for the increased production of reactive oxygen intermediates (ROI) by local inflammatory cells, which in turn increases their miracidicidal efficiency. Conversely, the relatively hypoxic environment of the liver decreases ROI production by local inflammatory cells and decreases their miracidicidal efficiency. PMID- 2319209 TI - Tumor necrosis factor-alpha gene expression in human whole blood. AB - Tumor necrosis factor-alpha (TNF) is recognized as a principal mediator of a variety of pathophysiologic and immunologic events. Lipopolysaccharide (LPS) challenge, either in vitro or in vivo, results in significant TNF production. In this study we present data demonstrating LPS-induced TNF mRNA expression and bioactivity using an in vitro tissue system of whole blood (WB). The kinetics of LPS-induced TNF production by WB was significantly accelerated as compared to isolated cultured peripheral blood monocytes (PBM). At post-LPS challenge, plasma from WB demonstrated a rapid rise in TNF bioactivity, peaking by 4 hr (1,021 units/ml/10(6) cells), plateauing between 4 and 8 hr, and then decreasing over the next 16 hr. In contrast, the highest measured TNF bioactivity from PBM did not occur until the 24-hr time-point (175 units/ml/10(6) cells). Whole blood buffy-coat TNF mRNA was assessed by Northern blot analysis, and demonstrated significant TNF mRNA accumulation at 1 hr and a peak 2 hr post-LPS challenge. By 8 hr TNF mRNA was undetectable. Concomitant administration of LPS with either prostaglandin E2 (10(-6)M) or Dexamethasone (10(-6)M) resulted in significant suppression of LPS-induced TNF production. This data supports WB as a useful in vitro medium for the molecular and cellular analysis of TNF. As specialized connective tissue, WB may provide an important environment to study the pharmacologic manipulation of TNF mRNA and bioactivity. PMID- 2319210 TI - Wavefront propagation in an activation model of the anisotropic cardiac tissue: asymptotic analysis and numerical simulations. AB - In this paper we present a macroscopic model of the excitation process in the myocardium. The composite and anisotropic structure of the cardiac tissue is represented by a bidomain, i.e. a set of two coupled anisotropic media. The model is characterized by a non linear system of two partial differential equations of parabolic and elliptic type. A singular perturbation analysis is carried out to investigate the cardiac potential field and the structure of the moving excitation wavefront. As a consequence the cardiac current sources are approximated by an oblique dipole layer structure and the motion of the wavefront is described by eikonal equations. Finally numerical simulations are carried out in order to analyze some complex phenomena related to the spreading of the wavefront, like the front-front or front-wall collision. The results yielded by the excitation model and the eikonal equations are compared. PMID- 2319211 TI - The singularly perturbed Hodgkin-Huxley equations as a tool for the analysis of repetitive nerve activity. AB - A qualitative analysis of the Hodgkin-Huxley model (Hodgkin and Huxley 1952), which closely mimics the ionic processes at a real nerve membrane, is performed by means of a singular perturbation theory. This was achieved by introducing a perturbation parameter that, if decreased, "speeds up" the fast variables of the Hodgkin-Huxley equations (membrane potential and sodium activation), whereas it does not affect the slow variables (sodium inactivation and potassium activation). In the most extreme case, if the perturbation parameter is set to zero, the original four-dimensional system "degenerates" to a system with only two differential equations. This degenerate system is easier to analyze and much more intuitive than the original Hodgkin-Huxley equations. It shows, like the original model, an infinite train of action potentials if stimulated by an input current in a suitable range. Additionally, explanations for the increased sensitivity to depolarizing current steps that precedes an action potential can be found by analysis of the degenerate system. Using the theory of Mishchenko and Rozov (1980) it is shown that the degenerate system does not only represent a simplification of the original Hodgkin-Huxley equations but also gives a valid approximation of the original model at least for stimulating currents that are constant within a suitable range. PMID- 2319212 TI - On polar auxin transport in plant cells. AB - We present here explicit mathematical formulas for calculating the concentration, mass, and velocity of movement of the center of mass of the plant growth regulator auxin during its polar movement through a linear file of cells. The results of numerical computations for two cases, (a) the conservative, in which the mass in the system remains constant and (b) the non-conservative, in which the system acquires mass at one end and loses it at the other, are graphically presented. Our approach differs from that of Mitchison's (Mitchison 1980) in considering both initial effects of loading and end effects of substance leaving the file of cells. We find the velocity varies greatly as mass is entering or leaving the file of cells but remains constant as long as most of the mass is within the cells. This is also the time for which Mitchison's formula for the velocity, which neglects end effects, reflects the true velocity of auxin movement. Finally, the predictions of the model are compared with two sets of experimental data. Movement of a pulse of auxin through corn coleoptiles is well described by the theory. Movement of auxin through zucchini shoots, however, shows the need to take into account immobilization of auxin by this tissue during the course of transport. PMID- 2319213 TI - Global behaviour of age-dependent logistic population models. AB - We study the large time behaviour of a nonlinear population model with a general logistic term. It is proved that every solution must have a limit when time becomes infinite. We present conditions that guarantee the boundedness of the solution. Furthermore, we prove that in general no oscillation is possible for the total number of population. This is in sharp contrast to the linear case. PMID- 2319214 TI - Applying brakes to the runaway American health care system. PMID- 2319215 TI - Private vs. universal health insurance. PMID- 2319216 TI - March in January: of reflections and crystal balls. PMID- 2319217 TI - The epidemiology of end-stage renal disease in Georgia. AB - We have examined the incidence of end-stage renal disease (ESRD) in Georgia in 1986 and 1987. We found high age-sex-race specific and total incidence rates compared to rates reported for other U.S. populations. Cause-specific and total ESRD incidence rates were significantly higher among blacks as compared to whites. In both races, the majority of new cases of ESRD occurring in Georgia during 1986 and 1987 can be attributed to diabetes or hypertension. Total ESRD rates were not uniform throughout the state; counties of the Coastal Plain (South) were significantly more likely to have higher rates than counties in the Piedmont Region (North). These patterns of ESRD in Georgia have implications for possible prevention efforts. PMID- 2319219 TI - OB/GYN across the pond. PMID- 2319218 TI - An economic analysis of the economic burden of cigarette smoking in Georgia. PMID- 2319220 TI - Resident physicians' involvement in organized medicine. PMID- 2319221 TI - Medical liability and neurologically impaired infants: a special approach to handling claims. PMID- 2319222 TI - Dealing with the new National Practitioner Data Bank. PMID- 2319223 TI - Radiation therapy of pure seminoma of the testicle. AB - An analysis of 45 patients with seminoma of the testis treated at the Radiation Oncology Department of Crawford Long Hospital of Emory University, from 1975 1986. Thirty patients with Stage I and II pure seminoma received prophylactic irradiation to the mediastinum and supraclavicular area in addition to receiving periaortic and pelvic irradiation alone. The only recurrence in the supraclavicular region was in a Stage I patient not receiving mediastinal and supraclavicular prophylaxis. No recurrences were observed in Stage II patients. The observed actuarial 5-year disease-free survival of all patients was 91.2%. In patients with Stage I disease, the actuarial 5-year survival was 93.3%. The actuarial 5 and 10-year survival of Stage II patients was 100%. PMID- 2319224 TI - 9th joint meeting of British Endocrine Societies. 19-22 March 1990, Glasgow. Abstracts. PMID- 2319225 TI - Excess retinoid acts through the stroma to produce mucous glands from newborn hamster cheek pouch in vitro. AB - Many morphogenetic processes are modified or initiated by retinoids. The cheek pouch of the newborn hamster can be induced to develop mucous glands in vitro by adding excess retinoid. The objective of this study was to determine whether the retinoid acted through the epithelium or the mesenchymal stroma. Explants of cheek pouch were grown for 7 days in either standard medium, or medium supplemented with 6 micrograms/ml retinyl acetate (RAc; 1.8 x 10(-5) M). After separation of most explants into epithelium and mesenchyme by trypsinization, the separated tissues were recombined in all possible ways and cultured for a further 1-2 weeks in standard medium. All explants were analysed histologically and/or histochemically from complete serial paraffin sections. No glands were formed in 30 recombinants containing stroma that had not been exposed to RAc, but four of 25 recombinants containing previously exposed stroma had glands, as well as four of 18 unseparated explants exposed to RAc. Exposure of epithelium to RAc did not result in the incidence of glands. It was concluded that RAc acting through the stroma was responsible for the instructive interaction with the epithelium for gland formation. A molecular mechanism is suggested. PMID- 2319226 TI - Biochemical study of prolactin binding sites in Xenopus laevis brain and choroid plexus. AB - The occurrence of prolactin binding sites in some brain structures (telencephalon, ventral hypothalamus, myelencephalon, hypophysis, and choroid plexus) from Xenopus laevis (anuran amphibian) was studied by the in vitro biochemical technique. The higher binding values were obtained at the level of the choroid plexus and above all of the hypothalamus. On the bases of hormonal specificity and high affinity, these binding sites are very similar to those of prolactin receptors of classical target tissues as well as of those described by us in other structures from Xenopus. To our knowledge, the present results provide the first demonstration of the occurrence of prolactin specific binding sites in Xenopus laevis choroid plexus cells. PMID- 2319227 TI - Highly polymorphic minisatellite sequences: allele frequencies and mutation rates for five locus-specific probes in a Caucasian population. AB - Six human minisatellite sequences (MS1, MS8, MS29, MS31, MS43, g3) have been subcloned into a stable host/vector system. Allele frequencies at the hypervariable loci detected by five of these probes were determined in a Caucasian population (200 individuals). Mendelian inheritance has been demonstrated in 5 large multi-generation pedigrees. The mutation rate has been determined in 59 families. The highest mutation rate was observed with MS1, as might be predicted from the observed high heterozygosity and in agreement with previous direct measurement of germ line mutation rates. The data presented on allele frequencies and mutation rates provide preliminary data supporting the use of these probes in paternity analysis and forensic investigations. PMID- 2319228 TI - Highly polymorphic minisatellite DNA probes. Further evaluation for individual identification and paternity testing. AB - Reliable and reproducible protocols have been developed for the routine DNA fingerprinting of individuals using the highly polymorphic minisatellite DNA probes 33.15 and 33.6. Comparison of DNA fingerprinting from 50 individuals has generated further data on the level of band sharing in the DNA fingerprints of unrelated individuals, as well as the number of bands scorable in individuals. These results are consistent with previous studies. The occurrence of mutant bands in offspring has been examined in over 100 families. Further support is presented for the Mendelian inheritance of minisatellite loci and for lack of significant allelism and linkage between different variable DNA fragments detected in a human DNA fingerprint. PMID- 2319229 TI - 1989 Firth memorial lecture. Working together. PMID- 2319230 TI - Issues in the identification of premenstrual syndromes. AB - Lack of information about the natural history of the premenstrual syndromes may make efforts regarding classification and treatment misguided. Thus, we report a naturalistic and noninstrusive approach to the problem of identification of the premenstrual syndromes, with particular focus on the issue of compliance with 2 months of daily prospective recordkeeping. Seventy-nine patients presenting for treatment of severe premenstrual symptoms were evaluated with a structured interview, psychological tests, and 2 months of daily prospective ratings of their symptoms. Weekly group follow-up meetings were held to foster compliance with recordkeeping. The typical woman seeking treatment for premenstrual symptoms in this study was middle-aged, highly educated, highly functioning, living in an urban setting, either married with children and family responsibilities or single and living alone, and supporting herself by a high-level job. She was anxious and depressed with multiple medical and gynecological problems. Despite a highly stressful life, she functioned at a very high level, but had consulted mental health professionals in the past. In general, she did not want medication. Consistent with other reports, only 20% of women seeking treatment for premenstrual symptoms had a premenstrual syndrome prospectively confirmed on the basis of 2 months of daily ratings. However, 81% of those with a prospectively confirmed premenstrual syndrome stated that after the 2-month evaluation period their symptoms no longer interfered with their functioning. PMID- 2319231 TI - Appraisal and coping in the process of patient change during short-term psychotherapy. AB - The process of patient change during short-term dynamic therapy was followed in eight patients by repeatedly measuring their appraisal and coping with significant people and issues in their lives. Patients' ratings of their appraisal and their coping with each of these variables were compared to a line of optimal functioning, which describes the ideal appraisal/coping relationship. Two groups of patients were identified who must carry out different corrections on these measures during therapy in order to approximate the optimal functioning line. The appraisal/coping relationship measure appears promising as a way to reflect patient change during therapy. PMID- 2319232 TI - Psychiatric epidemiology in Korea. Part I: Gender and age differences in Seoul. AB - The most dramatic finding was the very high prevalence of alcohol abuse, using DSM-III criteria, among men in Seoul, Korea. The prevalence of other psychiatric disorders was lower than in St. Louis, Missouri. With the current biological emphasis in psychiatry, questions may be raised regarding the different prevalence rates of schizophrenia, affective disorders, and even alcoholism. The deficit of the aldehyde dehydrogenase isoenzyme 1 has been hypothesized to reduce the prevalence of alcohol abuse among Asians. Twenty-five percent of Koreans have been found to be deficient in the enzyme, but despite this their prevalence of alcohol abuse is higher than among Americans. Cultural issues are paramount in the much lower prevalence of alcohol abuse among women in Korea. PMID- 2319233 TI - Neuropsychological deficits and violent behavior in incarcerated schizophrenics. AB - The authors studied 37 male schizophrenics in a county jail psychiatric unit. Subjects were classified as impaired or not according to Luria-Nebraska Neuropsychological Battery criteria. Twelve of the 37 patients were impaired. Violence ratings were made on inpatient behavior and adult criminal records. Impairment status was related to adult history of violence but not inpatient violence. The most violent patients (by criminal record) were from the impaired category. PMID- 2319234 TI - 2- versus 4-hour evening phototherapy of seasonal affective disorder. AB - Seasonal affective disorder (SAD) has been successfully treated with bright light, and morning exposure has been deemed more effective than exposure at other times. Evening treatment may offer a practical advantage, but the optimal duration of exposure has not been established. Six SAD patients were treated at home for 1 week with 2500 lux of light given either from 6 p.m. to 8 p.m. or from 6 p.m. to 10 p.m. using a counterbalanced crossover design with a minimal withdrawal period of 1 week between conditions. Both treatments were effective in reversing SAD symptoms, but neither treatment was superior. These results suggest that evening phototherapy for as little as 2 hours may be a useful and reasonable alternative for the treatment of SAD. PMID- 2319235 TI - Persistent auditory hallucinations and their relationship to delusions and mood. AB - Twelve patients who met DSM-III-R criteria for schizophrenia and had persistent auditory hallucinations completed a diary three times daily for 2 to 3 weeks. Using 5-point equal interval rating scales, nearly all patients were able to record consistently the nature of their hallucinations, the intensity of their delusional beliefs, and the mood and clarity of their thinking. For at least half the patients, there was a statistically significant relationship between the loudness and intrusiveness of hallucinations and the intensity of delusional beliefs; the more intrusive and distressing were the hallucinations, the more anxious and depressed were the patients. The findings suggested that more emphasis might be placed on altering patients' mood in the treatment of persistent hallucinations. The diary approach to research into auditory hallucinations appears promising. PMID- 2319236 TI - Absence of placebo response in obsessive-compulsive disorder. AB - Analyses in 30 patients with a diagnosis of obsessive-compulsive disorder given single-blind placebo over a 2-week period and of 12 of these patients who continued treatment on double-blind placebo for an additional 10 weeks revealed virtual absence of improvement on both clinician and self-rating scales of obsessions, compulsions, phobias, depression, and anxiety. This result would imply that the contribution of the placebo effect to the pharmacotherapy of patients with obsessive-compulsive disorder is negligible although considerable effort and work is still required to reliably identify one of four panic disorder with agoraphobia patients who respond to placebo. The placebo response thus presents a clear distinction between these two phenomenologically complex anxiety disorders. PMID- 2319237 TI - Mechanisms of synaptic competition. PMID- 2319238 TI - Mechanisms involved in activity-dependent synapse formation in mammalian central nervous system cell cultures. AB - Differences in neuronal activity produced by electrical stimulation lead to competition between synapses from sensory afferents converging on a common spinal cord neuron. Studies were performed on neurons dissociated from the mouse spinal cord and grown in culture dishes with three compartments. Synaptic efficacy from stimulated afferents was increased compared with unstimulated convergents, and the number of functional connections was increased by stimulation compared with control cultures. Blocking NMDA channel activation with 100 microM APV in medium containing 1.8 mM calcium inhibited this synaptic plasticity, but plasticity was not blocked by APV in medium in which the calcium concentration was elevated to 3 mM. These experiments support the view that electrical activity differentially influences processes that cause a persistent decrease in synaptic efficacy or lead to synapse elimination and those that increase synaptic strength or lead to synapse augmentation. We interpret our results in terms of a model in which these antagonistic mechanisms are both regulated via changes in calcium levels and second messengers that are modulated by electrical activity. A significant portion of the activity-related calcium influx relevant to synaptic plasticity passes through the NMDA channel, but other sources of calcium are involved. In particular, competitive elimination of synapses appears to occur during blockade of NMDA channels if the extracellular concentration of calcium is elevated moderately. The outcome of competition between the two calcium-dependent but antagonistic processes may depend either on their differential sensitivity to intracellular calcium concentration or separate specificities to NMDA and non NMDA receptor-linked mechanisms. PMID- 2319239 TI - Joint conference--American Paraplegia Society/American Spinal Injury Association 1989. Abstracts. PMID- 2319240 TI - American Paraplegia Society 1989. Abstracts. PMID- 2319241 TI - American Spinal Injury Association 1989. Abstracts. PMID- 2319242 TI - Comparative experience with intramedullary and extramedullary alignment in total knee arthroplasty. AB - A comparative analysis of intramedullary and extramedullary alignment was performed in 72 consecutive total knee arthroplasties, using the Moreland Knee Instrument System adapted for the Synatomic knee (DePuy). Six measurements were made from full-length anteroposterior radiographs taken 3 months after operation. Thirty-five of 40 (87.5%) of the intramedullary aligned patients had correct alignment (defined as 4 degrees-10 degrees of femoral component valgus). Using the same criterion, 22 of 32 (68.8%) of the extramedullary aligned patients were correctly aligned. The difference between intramedullary and extramedullary alignment was statistically significant at P less than .1. A correct tibiofemoral angle was achieved in 88% of the intramedullary aligned patients, compared to 73% of the extramedullary aligned patients. PMID- 2319243 TI - Dissociation of the glenoid component in the Macnab/English total shoulder arthroplasty. AB - Three episodes of mechanical glenoid component failure in two patients are presented. The glenoid component that failed is a two-piece polyethylene metal backed design, with a snap-fip interlock of the polyethylene insert. The mode of failure with this design should caution both orthopaedic surgeons and implant manufacturers that mechanical dissociation of a snap-fit glenoid liner can occur, and that discretion is advised in their design, fabrication, and use. PMID- 2319244 TI - Use of high-energy shock waves for bone cement removal. AB - The revision rate of total hip arthroplasty has increased dramatically over recent years, leading to different methods of extraction of the femoral cement mantle to reduce operative time and surgical risks. The use of high-energy shock waves produced by the Dornier HM.3 Lithotripter to interrupt the cement-bone interface and to reduce the material properties of the cement is investigated. Tests were conducted to measure the pull-out strength of cemented treated rods versus untreated rods, from the medullary canal of canine femurs. The treated femurs showed an average reduction in pull-out strength of 43%. An investigation involving the material properties of acrylic bone cement was also conducted. The properties tested were the compressive modulus of elasticity, the ultimate compressive strength, the ultimate tensile strength, and fracture toughness. The scanning electron microscope aided in determining whether microfractures in the cement resulted from the shock wave treatment. A theoretical study utilizing the finite element method was used to investigate areas of select shock wave treatment about the femoral prosthesis. Analysis of the results showed that the lithotripter treatment had no significant effect on the compressive properties but reduced the tensile properties and fracture toughness significantly. Scanning electron microscopy uncovered definite areas of induced microfractures not present in the control specimens. This study supports the concept of clinically noninvasive, preoperative shock wave treatment prior to total hip revision. PMID- 2319245 TI - Analysis of removed autophor ceramic-on-ceramic components. AB - Six Autophor alumina ceramic total hip arthroplasty components (5 removed for stem loosening and 1 for cup loosening) were evaluated to determine the nature and extent of wear by direct measurement, scanning electron microscopy of wear debris, and histology. Component implantation averaged 29 months (range, 8-54 months). All components had evidence of marked wear, including gross loss of material, which increased with the duration of implantation. PMID- 2319246 TI - Treatment of infected total knee arthroplasty. Irrigation and debridement versus two-stage reimplantation. AB - The results of 24 cases of deep wound infection after total knee arthroplasty were reviewed. Twenty-one knees were initially treated with irrigation and debridement. Infection recurred in 15 knees. An increased infection rate occurred after irrigation and debridement in patients in whom the index prosthesis was in place more than 2 weeks. Nine knees (including 7 that had removal after irrigation and debridement) were treated with removal of the infected prosthesis, intravenous antibiotics, and delayed reimplantation. Immediate exchange was done in one knee. There were no recurrences in this group (P less than .001). The final status of the patients included 8 with fusions or resection arthroplasties and 16 with a prosthesis. The average Hospital for Special Surgery knee rating was 41 in patients without a prosthesis and 75 in patients with a prosthesis (P less than .001). The authors conclude that irrigation and debridement is not likely to be successful for treatment of infections when used more than 2 weeks after the initial arthroplasty. Also, two-stage reimplantation for the treatment of infected total knee arthroplasties gives a reliably low recurrence rate and provides a superior clinical result, compared to arthrodesis or resection arthroplasty. PMID- 2319247 TI - Survivorship analysis of 1,041 Charnley total hip arthroplasties. AB - Survivorship analysis of 1,041 cemented Charnley total hip arthroplasties performed as a primary procedure revealed a probability of component survival at 10 years of 92%; the probability of acetabular cup survival was 99% and of femoral component survival was 96%. Three-zone acetabular demarcation was present in 16% of cases, as was migration of the cup greater than 5 mm. However, the acetabular revision rate was 1.65%, confirming the long-term clinical durability of the 22-mm internal diameter cup. Radiographic evidence of definite femoral component loosening was present in 9.6% and high-grade femoral bone-cement demarcation was present in 3.5%. The isolated femoral revision rate was 1.8%. Based on detailed survivorship analysis, a high-risk group of patients was identified for component failure and for femoral component loosening (radiographic). These patients were male, young (less than 50 years), heavy (greater than 170 pounds), and active (not Charnley class C). Given these findings, it is difficult to justify the widespread use of noncemented total hip systems, except in identifiable high-risk patients. PMID- 2319248 TI - Patellofemoral arthroplasty. 2-12-year follow-up study. AB - Seventy-two patellofemoral arthroplasties in 65 patients were followed an average of 4 years (range, 2-12 years). In 69 cases concomitant surgery was performed, including soft tissue realignments, tibial tubercle transfers, and unicompartmental femorotibial reconstructions. Twenty-two patients had already had knee procedures, 18 of which addressed their patellofemoral joint. The implant used in all cases features a deep, nonanatomic trochlear component. Using the Mansat scoring system, 85% of the results were good to excellent, with nearly 50% of these excellent. Fourteen complications were noted, seven related to the implant itself and seven associated with extrapatellar pathology. The authors have found patellofemoral arthroplasty to be a viable solution to end-stage patellofemoral arthritis, keeping in mind a nonforgiving surgical technique and the necessity to address all extraarticular pathology. PMID- 2319249 TI - Integrity of the gluteus medius after the transgluteal approach in total hip arthroplasty. AB - The postoperative integrity of the conjoined aponeurosis of the gluteus medius and vastus lateralis was studied in 97 consecutive total hip arthroplasties in 95 patients performed via a transgluteal approach. Metal markers were placed in the gluteal/vastus aponeurosis, one on each side of the suture line, and the integrity of the repair was assessed on radiographs taken immediately after surgery and 2 weeks, 2 months, and 1 year after operation. Separation between the markers occurred in about half of the patients, but gross separations were rare. Since most separations showed a progressive increment, elongation of the sutured aponeurosis might be a more common mechanism than perioperative injury to the neurovascular pedicle. Moreover, the degree of separation did not correlate with pain, and Trendelenburg gait was significantly increased only in the group of patients with a separation greater than 2.5 cm, indicating that a moderate gluteal elongation may be readily compensated for. PMID- 2319250 TI - Intraoperative autologous transfusion in primary and revision total hip arthroplasty. AB - Significant blood loss during total hip arthroplasty is usually unavoidable. Blood loss is even more of a problem during revision total hip arthroplasty. Using the Cell-Saver for retrieval of red blood cells to be used for autotransfusion during surgery is a safe and useful way of sparing donor blood transfusion. This is a retrospective analysis of primary and revision total hip arthroplasty cases and comparison between cases in which Cell-Saver was used versus those in which Cell-Saver was not used. Generally accepted standards to determine the need for blood transfusion, including measured serum hemoglobin and patient symptoms and vital signs, were used as guidelines in treating patients. Using multiple regression models and taking into account certain variables between cases, it was determined that a significant amount of donor blood transfusion can be saved when the Cell-Saver is used. The Cell-Saver is an important aid in intraoperative treatment for both primary and revision total hip arthroplasty cases. PMID- 2319251 TI - Removal of bone cement from the femoral shaft using a femoral windowing device. AB - The authors previously described a method of windowing the femur that allowed good exposure for femoral cement removal and provided for reconstruction of the defect. Since that report, they have developed instrumentation to facilitate windowing of the femoral shaft. They describe its use in this report. PMID- 2319252 TI - Effect of press-fit femoral stems on strains in the femur. A photoelastic coating study. AB - A photoelastic coating method was used to study the strain patterns on the surface of the femur, before and after insertion of femoral stems. The anatomically shaped stems were press-fit without a collar, press-fit with a collar, and press-fit with proximal cementing to approximate a bone ingrowth situation. The strain patterns of the intact femurs were consistent with bending. The pattern changed considerably after stem insertion, probably due to the stiffening effect of the stems. Nevertheless, the collarless press-fit stem preserved 64% of the magnitude of the proximal medial strain. The collar restored the average to normal, but the surface strains varied because of the localized regions of contact between the collar and the bone. Proximal cementing gave results similar to those of the collarless press-fit. The press-fit stems often showed local patches of high strain, probably reflecting local endosteal contact points. Local high stresses at the level of the distal tip were seen in only a few instances. PMID- 2319253 TI - A porous polyethylene-coated femoral component of a total hip arthroplasty. AB - The authors report their clinical experience with a femoral titanium stem with 3 mm of polyethylene (the outer 1.5 mm being porous) that was developed to function as a low-modulus type of prosthesis in an attempt to match the modulus of the prosthesis to the bone. The authors analyzed 223 of these stems of two different cross-sectional geometries: square (129) and round (94). Of these, 14 square and 5 round stems were subsequently replaced and all revealed only a fibrous ingrowth. Despite an average 82.4 Harris hip rating, 20% of the recipients still reported pain. For this reason the authors do not believe that the current design is adequate for the femoral component of a total hip arthroplasty. PMID- 2319254 TI - Functional outcome of hip fusion in the young patient. Follow-up study of 10 patients. AB - In the young patient, an osteoarthritic or osteonecrotic hip presents a challenging therapeutic problem. Until the long-term results of noncemented total hip arthroplasty are known, hip fusion provides an option to cemented total hip arthroplasty in the young patient with hip disease. The authors describe the outcome of hip fusion in 10 patients with an average follow-up period of 8.5 years. Seventy percent of the patients had a good or very good result with pain relief, and 90% or more had a good or excellent functional result with support aids, ambulation, and climbing stairs. All 10 patients were subjectively satisfied with their hip fusion. A lower incidence of pain in the contralateral hip, ipsilateral knee, and lower back was noted at 8.5 years than that reported at long-term follow-up evaluation and was associated with a satisfactory anatomic position of hip arthrodesis. PMID- 2319255 TI - A comparative study between McKee-Farrar and Charnley arthroplasty with long-term follow-up periods. AB - One hundred seventy-seven consecutive total hip arthroplasties on 169 patients, 107 with a McKee-Farrar prosthesis and 70 with a Charnley low-friction arthroplasty, were followed in a prospective study. Fifty-five patients (31%) representing 55 hips died during the study period. Four (2%), two McKee-Farrar and two Charnley, were lost to follow-up study. The remaining 55 McKee-Farrar and 41 Charnley hips were evaluated after a mean follow-up period of 11.5 years (range, 10.1-13.5 years). Twenty-two (12%) of the hips had been revised. A survival study was performed and the two techniques were compared with regard to walking ability, Harris hip score, and radiologic assessment. No major differences were observed. The mean annual revision rate in this series was 1.3%. Walking distance increased from 200 m before operation to 2,000 m 1 year after operation and then remained constant during the observation time. The results, using the Harris hip score, were good or excellent (greater than 80 points) in 47%. Thirty hips (32%) showed signs of prosthetic loosening; 17 of these caused pain on weightbearing occasionally or regularly and 13 caused no pain at all. PMID- 2319256 TI - Interferon therapy of relapsed and refractory Hodgkin's disease: Cancer and Leukemia Group B Study 8652. AB - A phase II trial of alpha 2b-interferon in patients with relapsed or refractory Hodgkin's disease was conducted by the Cancer and Leukemia Group B. Nineteen patients were eligible for study. These patients had received at least two (median of four) previous chemotherapeutic programs and 79% had received prior radiation therapy. Three patients had undergone intensive chemotherapy and autologous bone marrow transplantation. The treatment regimen consisted of interferon-alpha 2b 10 X 10(6) IU/m2 subcutaneously three times per week. Only limited antineoplastic activity was seen in this heavily pretreated group of patients. There was one partial response and four patients had reduction in measurable disease not meeting the criteria for partial response. The drug was well tolerated. Toxicity was predominantly myelosuppression. Thrombocytopenia was particularly severe in patients with bone marrow involvement. The observed antineoplastic activity, albeit limited, in this heavily pretreated group of patients suggests a potential role for this agent in combination regimens in patients with earlier disease. PMID- 2319257 TI - Human spleen and peripheral blood lymphocytes activated by interleukin-2 have similar phenotypic and functional characteristics. AB - Phenotypic markers and cytotoxic function were monitored in cultures of normal human mononuclear cells obtained from peripheral blood or spleen and stimulated by recombinant interleukin-2 (IL-2; 1,500 U/ml). Fresh spleen cells contained less than 5% natural killer (NK) cells (CD3-NKH1+), which increased about threefold after activation with IL-2. In both spleen and peripheral blood cultures, T cells with the NKH1 marker showed the highest relative increment among all cell types studied. Lymphokine-activated killer (LAK) cells from peripheral blood and spleen displayed very similar cytotoxic activity against K562, Daudi, and COLO carcinoma cell lines. Killing of the three targets peaked at 7 days of culture. Antibody-dependent cell cytotoxicity against a B-cell line was mediated by both circulating and splenic LAK cells from 2 to 14 days of culture. Cell sorting experiments showed that K562 targets were killed by both CD5+NKH1+ and CD5-NKH1+ cells whereas Daudi targets are only killed by CD5-NKH1+ activated NK cells from both spleen and peripheral blood. In summary, human spleen LAK cells have similar phenotypic and functional properties to circulating LAK cells, and they may be used for adoptive immunotherapy of human cancer. PMID- 2319258 TI - Interferon-alpha-n1 and continuous infusion vinblastine for treatment of advanced renal cell carcinoma. AB - Eighteen patients with advanced renal cell carcinoma were treated with human lymphoblastoid interferon (Wellferon) and continuous fusion vinblastine. All patients received vinblastine as a continuous infusion at a dose of 1.5 mg/m2/day on days 1 to 5. The interferon was given by daily intramuscular injections on days 1 to 10. Three patients were treated with a dose escalation scheme that reached a maximum daily dose by day 3 of 5 X 10(6) units/m2/day and that was then continued until day 10. Fifteen patients received 3 X 10(6) units/m2/day on day, 1, and 5 X 10(6) units/m2/day on days 3 to 10. Treatments were repeated every 28 days. Neutropenia (less than 1,500/mm3) occurred in 14 of 18 patients. Transient increases in serum glutamic-oxaloacetic transaminase levels to greater than four times baseline were noted in nine patients. Thrombocytopenia (less than 100,000 platelets/mm3) occurred in one patient. Fatigue, lethargy, and decline in performance status were marked in four of the patients. None of the patients in the low-dose interferon group and only 1 of the 15 patients in the high-dose interferon group had an objective response (7%, with a 95% confidence interval of 0 to 31%). Of the 12 patients completing at least two courses of therapy, 10 were in the high-dose group, which included the 1 objective (partial) response. This response noted at the start of the fourth course. Ten others developed progressive disease and one stopped treatment because of neurologic toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319259 TI - Macrophage activation by muramyl dipeptide bound to neoglycoproteins and glycosylated polymers: cytotoxic factor production. AB - Some biological functions of macrophages can be stimulated by muramyl dipeptide (MDP) in vitro. Such stimulation is more efficient when MDP is bound to macromolecule carriers. The macrophage stimulation by MDP bound to glycosylated serum albumin (BSA) or bound to gluconoylated and glycosylated poly-L-lysine (PLK) is investigated. These two types of MDP conjugates are more efficient than free MDP in rendering mouse peritoneal and rat alveolar macrophages cytostatic against various tumor cells. However, the release of mitogenic factor or cytotoxic factor (CF) by activated macrophages varies according to the nature of the carrier (BSA or PLK) and to the nature and content of sugar residues bound to the macromolecule carrier (mannose or 6-phosphomannose). Macrophages activated by MDP bound to glycosylated BSA release mitogenic factor and CF into the medium; anti-recombinant tumor necrosis factor (rTNF) totally inhibits the cytotoxicity of the supernatant. On the contrary, MDP bound to glycosylated PLK induces no secretion of mitogenic factor and a very small amount of CF in the culture medium. The role of CF in the cytostatic activity of activated macrophages is discussed. The released CF is not involved in the cytostatic activity, but TNF like molecules, expressed at the membrane level, could be implied because anti rTNF abrogates 40% of the cytostatic activity of the macrophages. PMID- 2319260 TI - Therapeutic efficacy of recombinant tumor necrosis factor alpha in an experimental model of human prostatic carcinoma. AB - Prostatic carcinoma represents the second leading cause of cancer mortality in men and is responsible for over 25,000 deaths each year. Currently, no curative therapy is available for metastatic carcinoma of the prostate. The present studies were undertaken to assess the efficacy of recombinant tumor necrosis factor alpha (TNF) in the therapy of experimental prostatic carcinoma. TNF was cytotoxic to the prostate cancer cell lines PC3, DU145, and LNCAP but not benign prostatic epithelial and stromal cells in vitro. The sensitivity of the prostatic carcinoma lines to TNF-mediated cytotoxicity was enhanced by the presence of actinomycin D. Intravenous administration of TNF (50-100 micrograms/kg) to nude mice bearing subcutaneous PC3 tumors resulted in significant inhibition of primary tumor growth compared to control. TNF was also effective in reducing the growth of intraabdominal PC3 tumors induced by intrasplenic injection of PC3. Furthermore, the incidence of microscopic PC3 foci in the spleen, liver, lung, and diaphragm was diminished in mice receiving TNF therapy. These studies demonstrate the potential of TNF in the therapy of human prostatic carcinoma. PMID- 2319261 TI - A pilot study of intralymphatic interleukin-2. I. Cytotoxic and surface marker changes of peripheral blood lymphocytes. AB - Patients with metastatic solid tumors were treated with six escalating doses of weekly intralymphatically injected recombinant interleukin 2 (i.l. IL-2). Nine patients completed the treatment and were evaluated for immunologic features of their peripheral blood lymphocytes (PBLs). The patients' PBL counts increased 4 days after the first i.l. IL-2 injection. The cell counts remained higher than baseline in week 6 prior to the last i.l. IL-2 injection. However, the PBL number decreased below baseline 1 day after the sixth injection, and recovered to normal levels after 3 days more. Natural killer (NK) activity showed similar changes when calculated as total activity per ml of blood. In vitro 1 h treatment of PBLs with IL-2 greatly enhanced NK cytotoxicity. The enhancement was only slight in the first week of i.l. IL-2 treatment, but was significantly greater on day 35 (7 days after dose 5) and day 39 (4 days after dose 6). In contrast, the increase was similar to the baseline on day 36, the day after the sixth injection. No lymphokine-activated killer activity was detected in the patients' PBLs with or without short-term in vitro IL-2 treatment. Besides the NK cytotoxic function, lymphoid subpopulations were evaluated numerically for total T cells (CD3/OKT3), T-cell subsets (CD4/OKT4 and CD8/OKT8), B cells (OKB7), NK cells (CD56/NKH1/Leu19, CD16/Leu11), and monocytes/NK cells (CD11b/OKM1). The activation markers (HLA-DR, CD25/Tac, and CD38/OKT10/Leu17) were also included. Intralymphatic IL-2 treatment had no effect on the PBL surface marker expression in the first week of treatment. However, by week 6, the percentages of cell populations expressing the NK-associated antigens CD56, CD16, and CD11b were significantly increased. In contrast, the percentage of CD3-positive T cells showed no change or a marginal decrease. Prior to and after i.l. IL-2 treatment, the CD56-positive cells in the PBLs were predominantly CD16 positive and CD3 negative. The i.l. IL-2 treatment did not induce PBL proliferation, or changes in the expression of CD25 (Tac), HLA-DR, CD38, CD4, CD8, CD57, or OKB7 in the patients' PBL. These results indicate that i.l. IL-2 treatment does affect the total number of PBLs, the cells expressing NK activity, and NK-associated surface markers. PMID- 2319262 TI - A pilot study of intralymphatic interleukin-2. II. Clinical and biological effects. AB - Interleukin-2 (recombinant methionyl human interleukin-2 alanine 125; IL-2) was administered intralymphatically to 12 patients with advanced cancer in a phase I trial. Doses were administered once a week for 6 weeks in a dosage escalation schedule; patients were entered in four groups at successively higher starting dosages. Toxicity occurred in a profile similar to that seen with intravenous IL 2. The maximum tolerated dose with this route/schedule was 275,000 units/kg, a figure not higher than expected with intravenous administration. T1/2 alpha was prolonged to 54 min from the 13 min figure we obtained with IL-2 given intravenously. Granulocytosis and eosinophilia were seen, along with lymphocytosis following initial lymphopenia. Anti-IL-2 antibodies were seen in 42% of patients (compared to 16% with this agent given intravenously), suggesting increased immunogenicity of this route/schedule. No clinical response was achieved. Immunologic effects will be reported separately but are summarized. PMID- 2319263 TI - Muramyl peptides and polyinosinic-polycytodylic acid given to mice prior to influenza virus challenge reduces pulmonary disease and mortality. AB - Muramyl dipeptide (MDP), murabutide (a derivative of MDP), mouse alpha-interferon (MoIFN), and polyinosinic-polycytodylic acid (poly (I-C) were tested in a mouse influenza virus model for anti-influenza virus activity. None of these compounds administered alone prior to virus challenge had more than minimal ability to protect mice from influenza virus infection. In contrast, mice given either MDP or murabutide 2 days prior to challenge with influenza A/Hong Kong/68 virus and poly I-C 1 day prior to virus challenge had significantly reduced pulmonary virus titers and mortality compared to comparably challenged control mice. No significant reductions in pulmonary virus titers or mortality were seen if MoIFN was given in place of poly I-C in this sequence. PMID- 2319264 TI - Impairment of language is related to left parieto-temporal glucose metabolism in aphasic stroke patients. AB - Twenty-six aphasic patients who had an ischaemic infarct in the territory of the left middle cerebral artery (MCA) were investigated. Cranial computed tomography (CT) showed various lesion sites: infarcts restricted to cortical structures in 12 patients, combined cortical and subcortical infarcts in 7 and isolated subcortical infarcts sparing the left cortex in another 7 cases. 18F-2-fluoro-2 deoxyglucose positron emission tomography revealed remote hypometabolism of the left convexity cortex and of the left basal ganglia, which was extended further than the morphological infarct zone in all cases. Types and degrees of aphasia were classified using the Aachener Aphasie Test (AAT): 10 patients had global aphasia, 2 Broca's, 5 Wernicke's, and 5 amnesic aphasia. Four patients suffered from minimal or residual aphasic symptoms. The AAT results were compared with the regional cerebral metabolic rates of glucose of the left hemisphere. Irrespective of the infarct location all five AAT subtests (Token test, repetition, written language, confrontation naming, auditory and reading comprehension) were closely correlated among each other and with left parieto-temporal metabolic rates, whereas left frontal and left basal ganglia metabolism showed no significant correlation. The close relation between left temporo-parietal functional activity and all five AAT subtests suggests that the different aspects of aphasia tested by AAT can be related to a common disorder of language processing in those areas. PMID- 2319265 TI - Natural history and outcome of psychogenic seizures: a clinical study in 50 patients. AB - The natural history and the outcome of psychogenic seizures was studied in 50 patients by retrospective analysis and follow-up after a mean of 2 years. Concomitant epilepsy was definite in only 8% and possible in 14%, while 50% took anticonvulsants. Overall, 66% of patients showed heterogeneous psychiatric abnormalities, most commonly a depressive syndrome (24%), whereas hysterical personality features were rare (8%). Forty-two percent of patients were unemployed. Follow-up of 41 patients (82%) showed that 34% had become seizure free. Outcome was poor in those with a long history of psychogenic seizures and pathological psychiatric findings. In contrast, almost all patients with recent onset of psychogenic seizures and normal psychological status had become seizure free. At follow-up, 56% of patients were found to be in a poor or very poor state, which resulted from a combination of physical, psychic and social problems in most cases. PMID- 2319267 TI - Giant aneurysm causing frontal lobe syndrome. AB - A 67-year-old patient with a completely thrombosed giant aneurysm of the anterior communicating artery is described. The only neurological findings were a disturbance of stance and gait and slight bilateral grasp reflexes. He had had the features of a frontal lobe psychotic syndrome for more than 12 years. Computed tomography demonstrated a primarily hyperdense calcified suprasellar space-occupying lesion. Magnetic resonance imaging proved valuable in establishing the correct diagnosis, which was confirmed post mortem. PMID- 2319266 TI - Loss of nerve fibres in the corpus callosum of progressive subcortical vascular encephalopathy. AB - The nerve fibres of the corpus callosum were studied by electron microscopy in five elderly patients with progressive subcortical vascular encephalopathy (PSVE) and compared with those in six age-matched controls. The number of nerve fibres per unit area of the corpus callosum was decreased in PSVE by 18-26%. The loss of nerve fibres in the corpus callosum can play a role in inducing the cognitive deficit of PSVE, on the basis of the loss of nerve fibres in the cerebral hemispheres. PMID- 2319268 TI - Borrelia burgdorferi myelitis presenting as a partial stiff man syndrome. AB - Eight weeks after a tick bite, a 33-year-old male patient presented with stiffness of one leg together with spasmodic painful jerks resembling stiff man syndrome. Isolated myelitis of lumbosacral segments of the spinal cord, apparently confined to the grey matter, was diagnosed and its spirochaetal aetiology confirmed by serology and CSF findings. Oligoclonal IgG bands in CSF specific for Borrelia burgdorferi were found. Thus, there is evidence that B. burgdorferi ist able to cause a localized myelitis, probably of spinal interneurons, presenting as a partial stiff man syndrome. PMID- 2319269 TI - Familial migraine coma: a case study. AB - A family suffering from a rare malignant type of migraine is described. The syndrome is characterized by episodes of coma with meningitic signs and fever and pareses as well as persistent cerebellar signs. Coma attacks last up to several days and can be precipitated by minor head trauma, vigorous work and angiography. From a study of this family and the literature, it is concluded that this syndrome has to be included in the differential diagnosis of coma and that angiography should be avoided in the patients. PMID- 2319270 TI - Polyradiculoneuritis following botulinum toxin therapy. AB - The development of Guillain-Barre syndrome is reported in a patient, who had previously received botulinum toxin type A injections into both orbicularis oculi muscles to treat idiopathic blepharospasm. The possibility of a causal relationship is discussed with consideration of the literature on adverse effects of vaccinations and of Clostridium botulinum and its toxin. PMID- 2319271 TI - Myopathy with nemaline structures associated with HIV infection. PMID- 2319272 TI - The specificity of the characteristic sleep EEG pattern in the fragile-X syndrome. PMID- 2319273 TI - Screening for snipers: the burden of proof. PMID- 2319274 TI - Misclassification of "probable senile dementia--Alzheimer's type" in the Baltimore Longitudinal Study of Aging. AB - Several papers in the literature refer to 27 men in the Baltimore Longitudinal Study as "probable Senile Dementia--Alzheimer's Type." The method used to identify these presumed cases was based on a retrospective review of archival records. An examination of the cognitive performance data of these 27 men is described in this report. Of the 27 presumed cases of SDAT, 15 had cognitive performance measures concurrent with (or later than) the latest historical records available for case identification; the cognitive data for 12 of those 15 men were inconsistent with SDAT. Conclusions based on the number and characteristics of these presumed cases of SDAT must be viewed with skepticism. PMID- 2319275 TI - The inadequacy of binary models for the clinical reality of three-zone diagnostic decisions. PMID- 2319276 TI - Temporal characterization of cancer occurrence. PMID- 2319277 TI - The relation of chlamydial infection of the cervix to time elapsed from the onset of menses. AB - To investigate the relation of chlamydial infection of the cervix to time elapsed from the onset of menses, we prospectively studied 338 women receiving routine gynecologic care in two clinical sites in which the prevalence of chlamydial infection was 3 and 6%. Eleven (13%) of 86 women evaluated in the fourth or fifth week after the onset of menses (days 22-35) had chlamydial infection compared to 4 (1.6%) of 252 women seen in the first 3 weeks (days 1-21) (p less than 0.001). For women seen in the fourth or fifth week, the relative risk of chlamydial infection was 8.1 (95% CI, 3.1-20.6). Controlling for known risk factors for chlamydial infection with multiple logistic regression analysis, the relative risk was sustained (RR 10.8; 95% CI, 3.1-37.4). We conclude that time elapsed from the onset of menses is an important independent risk factor for chlamydial infection of the cervix that may lead to more effective and efficient screening strategies. PMID- 2319278 TI - The association between aluminum-containing products and Alzheimer's disease. AB - The association between exposure to aluminum through the lifetime use of antiperspirants and antacids and Alzheimer's disease (AD) was explored in a case control study of 130 matched pairs. Cases were clinically diagnosed between January 1980 and June 1985 at two geriatric psychiatric clinics in Seattle, Wash. Controls were friends or non-blood relatives of the case. Subjects were matched by age, sex, and the relationship between the case and his or her surrogate. For all antiperspirant/deodorant use, regardless of aluminum content, there was no association with AD (adjusted odds ratio (OR) = 1.2, 95% CI = 0.6-2.4). For aluminum-containing antiperspirants, the overall adjusted OR was 1.6 (95% CI = 1.04-2.4) with a trend toward a higher risk with increasing frequency of use (p for trend = 0.03), the adjusted OR in the highest tertile being 3.2. For antacids regardless of aluminum content, the overall adjusted OR was 3.1 (95% CI = 1.2 7.9). Here, a steep dose-response gradient was found (p for trend = 0.009), with an adjusted OR for the highest tertile of 11.7. However, when only aluminum containing antacids were analyzed, the overall adjusted OR was only 0.7 (95% CI = 0.3-2.0) and there was no significant dose-response trend. These results are provocative but inconclusive due to methodologic problems relating to the necessary use of surrogate respondents and the long time period of potential exposure for this dementing disease. PMID- 2319279 TI - Fate of incorrectly addressed mailed questionnaires. AB - Mail surveys are a widely used and often inexpensive method for conducting epidemiologic studies, but may suffer from poor response rates. Some of this nonresponse may be due to letters that never reach study subjects rather than nonparticipation. We mailed letters to invalid addresses and to fictitious occupants at valid addresses in order to determine the proportion of letters that were not returned to us by the postal service as undeliverable. All letters mailed to invalid addresses were returned, whereas 13.3% (95% Cl 2.0-24.7%) of letters sent to fictitious occupants were not. Because some undeliverable mail is not returned, investigators may erroneously assume nonresponse for some subjects who never have the opportunity to participate. PMID- 2319281 TI - Sample size determination for pair-matched case-control studies where the goal is interval estimation of the odds ratio. AB - Samples sizes are calculated for case-control studies where 1:1 matching has been employed, and where the goal is the interval estimation of the odds ratio. The optimal sample size is defined to be the smallest value for which a 100(1 - alpha)% confidence interval for the log odds ratio will not exceed a specified width 2 delta with specified probability (1 - gamma). This approach is similar in spirit to the power-based approach for sample size determination when significance testing is the goal. Tables of sample sizes are presented for various choices of parameters. We also find considerable disagreement with a published method based on expected numbers of discordant pairs. PMID- 2319280 TI - Characteristics of stroke victims associated with early cardiovascular mortality in their children. AB - We assessed the relationship between characteristics of stroke victims and the risk of early death from coronary or cerebrovascular disease (CCVD) among their children. For each of 55 stroke patients selected from a registry which enrolled patients between 1969 and 1973, an index of their progeny's survival was calculated using the age in 1987 of 197 surviving children, and the age at and cause of death for 55 deceased children. Increased risk of CCVD death within families was significantly related to parental age at the time of first stroke, and with the parental history of diabetes mellitus. No significant relationship was found between the children's risk of CCVD death and the stroke patient/parent's sex, race, history of hypertension or cardiac disease, stroke diagnosis (infarction vs hemorrhage), or severity upon admission. These results suggest that family histories of cerebrovascular disease may impart differential risks, depending upon a family history of diabetes, and perhaps, the ages at which ancestral strokes first occurred. PMID- 2319282 TI - Purchase of antibiotics without prescription in Manila, the Philippines. Inappropriate choices and doses. AB - The purchase of antimicrobial agents in drugstores in a district in Manila. The Philippines was examined in order to determine how these agents might be used. Most antimicrobial agents are imported as bulk products and repackaged by a large number of small firms into 1491 different preparations including 206 marketed as combinations with other drugs. Antimicrobial agents accounted for 20.1% of all drug purchases. Purchases were made without prescription in 66.3% of 1608 transactions. Most of these were aminopenicillins or penicillins G or V (40.0%). The most common perceived indications were respiratory tract infections (20.2%), tuberculosis (8.8%), "prophylaxis" (8.6%) and gastrointestinal infection (8.3%). Almost 90% of purchases were for 10 or less capsules or tablets. The median number of units purchased was 3. Customers with written prescriptions purchased a mean of 8 while those who self-prescribed purchased a mean of 4 units (p = less than 0.05). We believe that these practices can provide only limited clinical efficacy and should favor emergence of resistant bacteria. PMID- 2319283 TI - A population-based study of craniosynostosis. AB - A population-based study of the incidence of craniosynostosis was conducted among residents of Olmsted County, Minnesota, born between 1 January 1976 and 31 December 1985. This study included only those with primary craniosynostosis who were less than 5 years of age at the time of diagnosis. Cases of craniosynostosis were classified as definite or probable. Definite cases had craniectomies or radiographic evidence confirming craniosynostosis, while patients for whom there was enough concern about craniosynostosis to order a skull radiograph were classified as probable cases. With these definitions, the incidence of craniosynostosis in Olmsted County was 3.1/10,000 births for definite cases (95% CI, 0.4-5.8) and 13.6/10,000 for all cases combined (95% CI, 7.9-19.3). These rates were compared to non-population-based minimal and maximal estimates of craniosynostosis frequency, 4/10,000 births and respectively. The rate observed in this study for definite cases, 3.1/10,000 births, is statistically consistent with the previous low estimate (observed/expected ratio 0.8, 95% CI, 0.2-1.8), and the rate observed for all cases in this study, 13.6, is consistent with the high estimate (observed/expected ratio 1.4, 95% CI, 0.8-2.1). Differences between definite and probable cases in this study are presented, along with comparisons with recent population-based data. PMID- 2319284 TI - Assessing the quality of life--a study in newly-diagnosed breast cancer patients. AB - Quality of life (QL) assessment is an increasingly important component of clinical research, especially with cancer patients. The literature strongly supports the view that QL should be assessed by the patient rather than the clinician. While clinical parameters such as performance status or toxicity ratings may bear some relationship to QL, they are not a substitute for its measurement. In spite of these observations, clinicians have been reluctant to accept the need for patient-rated measures of QL. In this paper, data from a sample of 109 newly-diagnosed breast cancer patients were used to examine the relationship between expert-rated measures and a patient-rated measure of QL; to determine whether the Cancer Rehabilitation Evaluation System (CARES), an instrument for assessing the rehabilitation needs of cancer patients, is a measure of QL; to explore whether there are any medical, social or demographic variables which the clinician can use to predict how patients assess their QL; and to determine which variables (expert-rated scales, medical, social or demographic variables, or rehabilitation needs) have the most effect on how patients evaluate their QL. In this sample, patient ratings of QL were widely distributed and were only moderately correlated with the expert-rated Karnofsky Performance Status (r = 0.53) and Global Adjustment to Illness Scale (r = 0.59). In addition, there were no significant correlations between important clinical variables (axillary node status, type of surgery, receipt of chemotherapy) and patient-rated QL. Among the clinical variables and instruments studied, the Global CARES score demonstrated the best correlation (r = -0.74) with the patient rated assessment of QL. A stepwise multiple linear regression procedure was performed with QL as the dependent variable in order to identify which factors accounted for the most variance in patient assessment of QL. The potential predictor variables used in this procedure were chosen from among those that would be available to a clinician. The Global CARES score was the best single predictor of QL, accounting for 55% of the variance, followed by Karnofsky Performance Status, the Medical Interaction and Sexual summary scales of the CARES, and the patient's educational status. Data from the CARES provided additional descriptive information about the type and frequency of rehabilitation problems experienced by these patients in relation to their ratings of QL.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2319285 TI - Recall bias in epidemiologic studies. AB - The factors which contribute to bias due to differential recall between cases and controls in retrospective studies have been little studied. A review of the literature on recall accuracy suggests that the extent of inaccurate recall is related to characteristics of the exposure of interest and of the respondents, though a distinction must be drawn between recall which is biased and that which is simply inaccurate. Interviewing technique and the study protocol, including the design of questionnaires and the motivation of respondents, play a central role and are under the control of the investigator. The results of validation studies carried out to date suggest that the likelihood of recall bias may be greater when recall is poor in general. PMID- 2319286 TI - The effect of the number of electrocardiograms analyzed on cardiovascular disease surveillance: the Minnesota Heart Survey (MHS). AB - One method used to control costs in community cardiovascular disease surveillance is to limit the number of electrocardiograms (ECGs) used to validate acute myocardial infarction (AMI). The Minnesota Heart Survey investigated the impact of decreasing the maximum number of ECGs analyzed on classification of ECG pattern and final AMI diagnosis (definite, probable, none). A 50% sample of all 1980 acute CHD hospital discharge records (ICD-9 code 410 or 411) from 30 of 31 Twin Cities hospitals were abstracted. Comparing results using all available ECGs in the record (maximum of 12) with those obtained using up to 4 ECGs showed little differences in the ECG classification or final AMI diagnosis. PMID- 2319287 TI - Radioimmunoassay of glioma-associated antigen in cerebrospinal fluid and its usefulness for the diagnosis and monitoring of human glioma. AB - Quantitative determination of human glioma-associated antigen in cerebrospinal fluids (CSFs) obtained from 66 patients with a variety of neurological diseases was performed by solid-phase radioimmunoassay with a monoclonal antibody (G-22). In this system, the minimum detectable amount of the antigen in the CSF was 8 ng/ml. It was demonstrated that CSF diagnosis of glioblastoma might be possible in the case of small tumors with a diameter of less than 2 cm. CSFs obtained from all 18 patients with glioma were positive and the level varied from 11.2 to 186.1 ng/ml. The antigen level in the cystic fluid of the tumor was higher than that in CSF. There was a tendency for the antigen level in CSF to be correlated with the tumor size and the type of histology. The malignant types of glioblastoma or medulloblastoma showed higher levels than the benign type of ependymoma and astrocytoma. Most types of non-gliomatous brain tumor were negative except immature teratoma, meningioma with central neurofibromatosis, and metastatic brain tumor from lung cancer. We also noted that tumor progression or regression of malignant glioma could be predicted by the monitoring of the antigen in the CSF. PMID- 2319288 TI - An immunocytochemical comparison of glial fibrillary acidic protein, S-100p and vimentin in human glial tumors. AB - Immunostaining patterns of glial fibrillary acidic protein (GFAP), S-100 protein (S-100p) and vimentin were studied using immunohistochemical techniques on 48 paraffin embedded glial tumors. GFAP was positive in all tumor cases except in two oligodendrogliomas. S-100p was found in most astroglial tumors and in half of the oligodendrogliomas. Vimentin was positive in many astrocytomas but in no oligodendrogliomas. Most astroglial tumors showed similar immunoreactivity for GFAP and S-100p. Fibrillary processes, however, showed stronger and more crisp staining with anti-GFAP than with anti-S-100p, whereas cell nuclei were labeled only for S-100p. Vimentin was localised mainly in juxtanuclear positions. In many astrocytomas with different degrees of malignancy co-expression of GFAP, S-100p and vimentin was found. The presence of GFAP and S-100p was not correlated with the degree of differentiation in astrocytomas. Vimentin was more positive in anaplastic astrocytomas but this finding was not statistically significant. It seems that GFAP is a superior marker to S-100p and vimentin in the identification of human gliomas. PMID- 2319289 TI - Sensitivity of human malignant intracranial tumors against MCNU in vitro in comparison to ACNU and BCNU. AB - An in vitro chemosensitivity test was carried out in 50 specimen of human malignant intracranial tumors. Aim of the study was to evaluate the proportion of sensitivity against MCNU (Ranomustine) in comparison to ACNU and BCNU. 47 tests were evaluable. Mean viability of the specimen was 83.3 +/- 18.7%, mean plating efficiency was 0.068 +/- 0.051%. 9/47 settings revealed sensitivity against MCNU in vitro (ACNU: 10/47; BCNU: 16/46). There was no advantage of MCNU concerning age or sex of the patients. Brain metastases seemed to be slightly more frequent sensitive against MCNU than primary brain tumors. Cross resistance between ACNU, BCNU and MCNU was rather high. The results of this in vitro series do not encourage a clinical trial of MCNU as an alternative to the commonly used nitrosoureas. PMID- 2319290 TI - Failure of betamethasone to alter the radiation response of two cultured human glioma cell-lines. AB - Glucocorticoids, such as betamethasone, are often used to prevent possible acute reactions during radiation therapy of intracranial tumors (for example gliomas). The effect of the glucocorticoids is probably due to vascular changes decreasing the development of edemas. The radiosensitivity of two studied cell-lines of human malignant glioma origin did not significantly change when they were continuously exposed to betamethasone in the concentration range of 1-25 micrograms/ml. The radiosensitivity was measured with the extrapolation method, which gave an estimate of cell survival, and through direct measurements of growth delays from growth curves. The results obtained are in conformity with previously published results where clonogenic survival tests showed that the isomer dexamethasone did not change the radiosensitivity of these cells. Thus, no direct effects on the radiosensitivity of glioma cells are expected from glucocorticoid treatment and it is therefore unlikely that the poor results obtained from radiation therapy of malignant gliomas are due to an increased radioresistance brought on by the glucocorticoid treatment. PMID- 2319291 TI - Nonoccupational risk indicators of glioblastoma in adults. AB - A case-control study of brain tumor was conducted in collaborating hospitals in Boston, Providence, and Baltimore. Cases were 160 consecutive patients being treated for glioblastoma, grade 3 or 4 astrocytoma, or anaplastic astrocytoma. Controls were 128 healthy persons identified among the case's friends. A complex self-administered questionnaire was used to assess exposure to factors of interest. There was some evidence that glioblastoma is associated with a decreased susceptibility to allergies, a finding that may call attention to the involvement of immunologic disturbances in brain tumors. Our data are not supportive of previous reports of an association between brain tumors and exposure to pets or farm environment, family history of CNS malignancies or other neurologic conditions, or irradiation to the head. We did not find any evidence for an association with life-style characteristics such as cigarette smoking, alcohol consumption, use of drugs of any kind, or dietary intake of cured or smoked meat or fish. PMID- 2319292 TI - Lack of efficacy of megestrol acetate in the treatment of unresectable meningioma. AB - The detection of hormone receptors on meningiomas raises the possibility of hormonal manipulation as a form of therapy. Since progesterone receptors are found on meningiomas more frequently and in greater amounts than estrogen receptors, manipulation of progesterone levels would be most promising. A trial of the oral progesterone agonist megestrol acetate for the treatment of unresectable meningioma was therefore performed. Megestrol acetate was administered at a dose of 40 mg four times daily which could be escalated to 80 mg four times daily. Nine patients (six meningothelial, two fibrous, and one anaplastic meningiomas) were treated for 1 to 12 months. No tumor responses were seen. However three patients required discontinuation of therapy due to deteriorating vision within 2 1/2 months. The major systemic toxicity of megestrol acetate was weight gain with a median weight gain of 14 kg for patients treated for at least 6 months. Due to the lack of efficacy and the significant toxicity noted, megestrol acetate is not recommended for the treatment of meningioma. However clinical trials of progesterone antagonists would still be of interest. PMID- 2319293 TI - Gliomas following low-dose irradiation to the head report of three cases. AB - Three patients developed cerebral gliomas decades after exposure to low-dose x ray irradiation in childhood for the treatment of tinea capitis. One of the patients had a glioblastoma multiforme concomitant with multiple intracranial meningiomas, a condition highly correlated with previous irradiation. The other tumors were malignant cerebellar astrocytoma and a diffuse cerebral astrocytoma. We review the evidence suggesting that low-dose irradiation is involved in the pathogenesis of gliomas. PMID- 2319295 TI - Combined treatment of anaplastic astrocytoma (grade 3-4) with diacetyl-dianhydro galactitol (DADAG). AB - Autoradiographic studies of labeled diacetyldianhydro-galactitol (DADAG) with tumor bearing animals revealed that the CNS accumulates high amounts of DADAG derived radioactivity and the elimination from the brain seems to be relatively slow. This observation and the activity of DADAG against murine ependymoblastoma classified the drug as a promising agent for the treatment of malignant brain tumors. In a series of 30 evaluable consecutive patients who were operated on for anaplastic astrocytomas, DADAG has been applied during and subsequent to postoperative radiotherapy. No severe toxicity occurred. Survivals were compared with a group of patients who got irradiation alone. Statistical analysis did not show significantly better survivals in the DADAG treated group: median value was 46.5 weeks, p = 0.232. PMID- 2319294 TI - Vascular response to irradiation in malignant gliomas. AB - The vascular response to irradiation was studied in peritumoral cortex and tumor areas in 9 autopsied cases of glioblastoma multiforme and in 10 biopsies of reoperated cases. The study was carried out by histological, immunohistochemical and electron microscope procedures. Hyaline thickening of the vessel walls with deformation and impoverishment of endothelial nuclei are the most striking features. Formation of large PAS-positive areas from the confluence of thickened vessel walls and development of a fibroblastic proliferation follow. Fibroblastic areas may entrap tumor glial cells. In PAS-positive areas a special population resembles myofibroblasts of tissue scars. Electron microscope reveals the production of collagen fibrils in and outside vessel walls. The presence of collagen III and IV is in line with the present interpretation of the mesodermic component. PMID- 2319296 TI - Postoperative radiotherapy and radiotherapy combined with CCNU chemotherapy for treatment of brain gliomas. PMID- 2319297 TI - Intracranial C6 glioma model in adult Wistar-Furth rats. PMID- 2319298 TI - Selective expression of an endogenous lactose-binding lectin gene in subsets of central and peripheral neurons. AB - Cellular interactions in a variety of vertebrate non-neural tissues are thought to be mediated by cell surface carbohydrate structures. The detection of cell specific surface carbohydrates and carbohydrate-binding proteins within the embryonic nervous system has raised the possibility that carbohydrate recognition may also contribute to the interactions of developing neurons. Soluble lactose binding lectins constitute one class of carbohydrate-binding proteins expressed in the vertebrate nervous system. We describe here the isolation of cDNAs from rat brain libraries encoding one of these lectins, RL-14.5, and demonstrate that this protein is not only homologous to other soluble lectins, but also identical in primary sequence to a lectin present in at least one non-neural tissue. RNA blot analysis and in situ hybridization reveal a restricted pattern of expression of RL-14.5 mRNA within the rat nervous system. High levels of RL-14.5 mRNA are present in primary sensory neurons and motoneurons in the spinal cord and brain stem. Moreover, expression of RL-14.5 mRNA in sensory and motoneurons is detectable soon after neuronal differentiation. These findings, together with previous studies demonstrating the selective expression of oligosaccharide ligands for RL-14.5 on the same neurons, are consistent with the idea that carbohydrate-mediated interactions contribute to the development of this subset of mammalian neurons. PMID- 2319299 TI - Fictive locomotion in the fourth thoracic ganglion of the crayfish, Procambarus clarkii. AB - Bath application of muscarinic agonists induced rhythmic motor activity in an in vitro preparation of the thoracic nervous system of the crayfish, Procambarus clarkii. In 70% of the cases, the rhythm was organized into 1 of the 2 normal patterns: "backward" walking or "forward" walking. In the rest (30%), the ganglion produced either a series of bursts of impulses or no rhythm at all, just an increase in the tonic activity. When it was isolated from all ascending and descending afferents, the fourth thoracic ganglion was still able to generate rhythmic motor output during bath application of muscarinic agonists. In certain motor neurons, muscarinic agonists induced plateau potentials. Under these conditions, some of these motor neurons were able to change the period of the motor pattern, which might suggest that these motor neurons were part of the central pattern generator (CPG) for locomotion. In the presence of 5 x 10(-6)M TTX, the membrane potential of these motor neurons continued to oscillate with organized rhythmic membrane potential oscillations into 1 of the 2 patterns. Under these conditions, current injection into certain motor neurons demonstrated that they continued to affect the CPG. Two classes of walking leg interneurons have been found. First, there are those with a sustained membrane potential: injection of a steady depolarizing current into some of these interneurons induced rhythmic activity in all thoracic motor nerves, even in the absence of any pharmacological activation. Second, there are those with an oscillating membrane potential: these seemed to enable silent motor neurons to be involved in an ongoing rhythm. PMID- 2319300 TI - Patterns of cell and fiber vulnerability in the mesostriatal system of the mutant mouse weaver. II. High affinity uptake sites for dopamine. AB - Weaver (gene symbol wv) is an autosomal recessive mutation in the mouse that causes the death of neurons in the cerebellum and of dopamine-containing neurons in the mid-brain. In the accompanying paper and in previous reports, the selective nature of the deficit produced by the gene in the dopamine-containing systems has been described after analysis of the patterns of the residual innervation in the striatum and the patterns of cell death in the midbrain. In the present report, we describe deficits in the terminals of the mesostriatal system occurring prior to a detectable dopamine deficiency in the striatum and prior to the onset of cell death in the mesencephalic dopamine-containing neurons during development. We have also found deficits in the remaining terminals of the adult weaver's striatum after the weaver pattern of innervation has been permanently established. Axonal terminals in the caudoputamen are impaired in weaver mice at postnatal day 7, before the onset of dopamine depletion in the caudoputamen and cell death in the midbrain. The impairment was revealed by a markedly deficient high-affinity uptake for 3H-dopamine by synaptosomes prepared from the caudoputamen. Throughout the remainder of development and in adulthood, the extent of the deficit in 3H-dopamine uptake was always greater than that for dopamine content. No striatal region was completely spared the effects of the gene. In the nucleus accumbens of the weavers, where dopamine content is normal, 3H-dopamine uptake was reduced by 35% in the synaptosomal preparations. In the olfactory tubercle, dopamine levels were reduced by 44% but 3H-dopamine uptake was reduced by 60%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319301 TI - Chronic naltrexone treatment increases expression of preproenkephalin and preprotachykinin mRNA in discrete brain regions. AB - Long-term blockade of brain opioid receptors by the opiate antagonist naltrexone increases methionine-enkephalin content in the striatum and nucleus accumbens (Tempel et al., 1984). To determine whether these changes in peptide levels reflect increased peptide synthesis, we examined preproenkephalin mRNA content in discrete brain regions of control (placebo-treated) and chronic naltrexone treated animals by Northern analysis. Chronic naltrexone treatment (8 d) led to an approximately 12-fold increase in the striatal content of preproenkephalin mRNA relative to that of control animals. In contrast, no statistically significant change was observed in striatal mRNA for cyclophilin (1B15) or actin. Small increases in preproenkephalin mRNA content occurred in the hippocampus (+40%) and hypothalamus (+19%). No significant changes occurred in the frontal cortex. Increases in levels of the mRNA were seen as early as 24 hr after antagonist treatment. In contrast, changes in opioid receptor density required 3 4 d to reach half-maximal up-regulation after chronic antagonist treatment. Recent evidence has suggested that substance P is regulated by opioid peptides. To determine whether substance P synthesis is altered by chronic antagonist treatment, the mRNA corresponding to the precursor for substance P was examined using a probe for exon-7 of the preprotachykinin gene. Preprotachykinin mRNA content in the striatum was increased 6-fold after chronic antagonist treatment relative to that of control animals. Substance P content was increased 3-fold after chronic antagonist treatment. These data suggest that chronic blockade of brain opioid receptors leads to the increased synthesis of both enkephalin and substance P in the striatum and that these changes are relatively specific.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319302 TI - Electrophysiological properties of neuroendocrine cells of the intact rat pars intermedia: multiple calcium currents. AB - Intracellular recordings for current and voltage clamping were obtained from 130 neuroendocrine cells of the pars intermedia (PI) in intact pituitaries maintained in vitro. Spontaneous and evoked action potentials were blocked by TTX or by intracellular injection of a local anesthetic, QX-222. After potassium (K+) currents were blocked by tetraethylammonium (TEA), 4-aminopyridine, and intracellular cesium (Cs+), 2 distinct calcium (Ca2+) spikes were observed which were differentiated by characteristic thresholds, durations, and amplitudes. Both Ca2+ spikes were blocked by cobalt (Co2+) but were unaffected by TTX or QX-222. The low-threshold spike (LTS) had a smaller amplitude and inactivated when membrane potential was depolarized past -40 mV or when evoked at a fast rate (greater than 0.5 Hz). The high-threshold spike (HTS) typically had a larger amplitude and longer duration, was not inactivated at potentials which inactivated the LTS, and could be evoked at rates of up to 10 Hz. Single electrode voltage-clamp analysis revealed that 3 distinct components of the Ca2+ current were present in most cells. From a negative holding potential (-90 mV), 2 separate peak inward currents were observed; a low-threshold transient current, similar to a T-type Ca2+ current, activated at -40 mV, whereas a large-amplitude inactivating current activated above -20 mV. This large inactivating Ca2+ current was significantly inactivated at a holding potential of -40 mV or by brief prepulses to positive potentials, and was similar to an N-type Ca2+ current. A sustained Ca2+ current (L-type) was observed which was not altered by different holding potentials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319303 TI - Input and output connections of an anteromedial group of spiking local interneurons in the metathoracic ganglion of the locust. AB - Intracellular recordings were made from an anteromedial group of spiking local interneurons in the metathoracic ganglion of the locust to determine the input connections that shape their mechanoreceptive fields on a hindleg and the output connections that define their effects on hindleg motor neurons. The receptive fields of these interneurons may contain excitatory and inhibitory regions. An excitatory region on the ipsilateral hind leg is formed by direct excitatory connections of the afferents from exteroceptors. Afferent spikes consistently evoke EPSPs in interneurons with a central synaptic latency of 1.2-1.5 msec. The connections appear to be direct and chemically mediated. An inhibitory region of a receptive field is not formed by direct afferent connections. Instead, spiking local interneurons of a midline group, which also receive direct excitatory inputs from the afferents, make direct inhibitory connections with anteromedial interneurons. Spikes in particular midline interneurons consistently evoke IPSPs in anteromedial interneurons with a central synaptic latency of about 1.0 msec. The connections appear to be direct and chemically mediated. By contrast, spikes in anteromedial interneurons could not be linked to any synaptic potentials in midline interneurons, so that direct connections are unidirectional and inhibitory. The large inhibitory regions to the receptive fields of anteromedial interneurons result from convergent inhibitory inputs of several midline interneurons. Each midline interneuron may make inhibitory output connections with several anteromedial interneurons, but there is a high degree of specificity in these divergent connections. Anteromedial interneurons make excitatory output connections with specific hind leg motor neurons. EPSPs in motor neurons follow spikes in the interneurons with short and consistent synaptic latencies of about 1.0 msec. The connections appear to be direct and chemically mediated. Two or more anteromedial interneurons with overlapping receptive fields may converge onto one motor neuron, and, in turn, one interneuron may make divergent connections with several motor neurons of the same pool. This pattern of connections suggests that these interneurons are essential elements in the local circuitry responsible for the expression of local reflexes of a leg. They provide an excitatory drive to the motor neurons in parallel to that from nonspiking local interneurons when particular arrays of exteroceptors are stimulated. PMID- 2319304 TI - The time course and amplitude of EPSPs evoked at synapses between pairs of CA3/CA1 neurons in the hippocampal slice. AB - Unitary EPSPs were evoked in CA1 pyramidal neurons by activation of single CA3 pyramidal neurons. Seventy-one EPSPs were recorded. The peak amplitudes of these EPSPs ranged from 30 to 665 microV with a mean of 131 microV. Rise times and half widths were measured, the means +/- SD being 3.9 +/- 1.8 and 19.5 +/- 8.0 msec, respectively. The time courses of these EPSPs were consistent with a brief synaptic current at a localized electrotonic region of the dendritic tree followed by passive spread of current to the soma. EPSPs varied in amplitude from trial to trial. Sufficient records were collected for 12 EPSPs to demonstrate that this variation was greater than could be accounted for by baseline noise. The amplitude variations of one EPSP were reliably resolved from the background noise, and this EPSP fluctuated between 4 discrete amplitudes (including failures) separated by a quantal increment of 278 microV. PMID- 2319305 TI - Insect olfactory neurons in vitro: morphological and immunocytochemical characterization of male-specific antennal receptor cells from developing antennae of male Manduca sexta. AB - Sex-pheromone components released by Manduca sexta females are detected solely by male-specific olfactory receptor neurons that innervate long sensilla trichodea on the male antennae. To facilitate studies of the development and physiology of these receptor cells, we have produced primary in vitro cultures of cells dissociated from pupal male antennae. These cultures comprise several morphological types of cells, 2 of which have been characterized immunocytochemically with a pair of monoclonal antibodies that were shown previously to recognize certain antigens in olfactory receptor neurons at defined stages of development. The good correlation between in vivo and in vitro expression of these antigens suggests that the immunocytochemically recognized cells are olfactory receptor neurons that follow at least partially their normal course of differentiation in vitro. PMID- 2319306 TI - Local cerebral glucose utilization in monkeys with hemiparkinsonism induced by intracarotid infusion of the neurotoxin MPTP. AB - Quantitative 2-[14C]deoxyglucose autoradiography was used to map the pattern of alterations in local cerebral glucose utilization associated with unilateral lesions of the substantia nigra pars compacta produced by the infusion of 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into one internal carotid artery of rhesus monkeys. These monkeys become hemiparkinsonian, displaying rigidity, bradykinesia, and tremor of the limbs contralateral to the side of MPTP infusion; during spontaneous activity they turn toward the side of the lesion. Eighty-two brain areas were examined, and statistically significant metabolic changes were confined mainly to basal ganglia structures ipsilateral to the side of the lesion. Glucose utilization was reduced in the substantia nigra pars compacta and ventral tegmental area, i.e., in the areas of cell loss. Increases in glucose utilization in regions normally innervated by the lesioned area were observed in the post-commissural portions of the putamen and dorsolateral caudate. Other structures showing statistically significant metabolic changes were the external segment of the globus pallidus (+40%), subthalamic nucleus ( 17%), and pedunculopontine nucleus (+15%). There were also smaller changes in portions of the thalamus (ventral anterior nucleus, parafascicular nucleus) and premotor cortex. All significant metabolic changes were confined to the side of the substantia nigra lesion and were essentially restricted to regions involved in the production of movement or maintenance of posture. PMID- 2319307 TI - Androgen regulation of dendritic growth and retraction in the development of a sexually dimorphic spinal nucleus. AB - The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic group of motoneurons whose development and maintenance are under androgenic control. Exposure to androgens early in development permanently alters SNB motoneuron number and soma size; in adulthood, androgens regulate dendritic and synaptic architecture. The present set of experiments investigates the influence of androgens on the development of SNB dendritic morphology. In normal males, SNB dendritic growth is biphasic, reaching exuberant lengths by the fourth postnatal week and then retracting to adult lengths by 7 weeks of age. This dendritic growth is androgen dependent--males castrated on postnatal day (P) 7 and given daily injections of testosterone propionate (TP) had exuberant dendritic lengths similar to those of normal males; dendritic length in oil-treated males remained at P7 levels. The early exuberant dendritic length was retained in TP-treated males through P49. The retraction of SNB dendrites after P28 is also influenced by androgens. Males castrated at P28 and given testosterone implants retained exuberant dendritic length at P49; blank-implanted males had significantly shorter dendritic lengths by P70. These results suggest that androgens are necessary for the early exuberant growth of SNB dendrites. Furthermore, the subsequent retraction of SNB dendrites may be halted when testosterone titers reach a critical level during puberty, stabilizing their adult length. PMID- 2319308 TI - Sex differences and thyroid hormone sensitivity of hippocampal pyramidal cells. AB - In an effort to determine if sex differences exist in the morphologic characteristics of pyramidal cells and granule cells of the hippocampal formation and whether sex plays a role in determining thyroid hormone sensitivity of these neuronal populations, we used single-section Golgi impregnation to examine the effects of neonatal thyroid hormone administration on hippocampal cells from the brains of adult rats of both sexes. Quantitative analyses of control brains revealed sex differences in the number of primary dendrites and the number of spines on the apical dendritic shaft of CA3 pyramidal cells. These differences showed opposite trends; females possessed more primary dendrites, whereas males showed more apical excrescences. Neonatal treatment with thyroid hormone resulted in long-lasting and dramatic changes of the entire CA3 pyramidal cell. CA3 pyramidal cells from thyroid hormone-treated animals showed significantly larger cell body areas, greater numbers of dendritic branchpoints, and longer dendrites. In addition, CA3 pyramidal cells from thyroid hormone-treated animals showed changes in the morphological characteristics which were shown to be sexually dimorphic; treatment resulted in significantly greater numbers of both primary dendrites and apical excrescences. These treatment differences occurred in both sexes and were of equal magnitude, regardless of sex. On the other hand, no sex differences in the morphologic parameters examined were detected for pyramidal cells in the CA1 region. Moreover, neonatal thyroid hormone treatment did not affect the cell body area, dendritic branch points, or the length of dendrites of these cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319309 TI - Intramedullary ependymoma of the spinal cord. AB - A consecutive series of 23 patients underwent operative removal of an intramedullary spinal cord ependymoma between January, 1976, and September, 1988. Thirteen women and 10 men between the age of 19 and 70 years experienced symptoms for a mean of 34 months preceding initial diagnosis. Eight patients had undergone treatment prior to tumor recurrence and referral. Mild neurological deficits were present in 22 patients on initial examination. The location of the tumors was predominantly cervical or cervicothoracic. Radiological evaluation revealed a wide spinal cord in all cases. Magnetic resonance (MR) imaging was the single most important radiological procedure. At operation, a complete removal was achieved in all patients. No patient received postoperative radiation therapy. Histological examination revealed a benign ependymoma in all cases. The follow-up period ranged from 6 to 159 months (mean 62 months) with seven patients followed for a minimum of 10 years after surgery. Fourteen patients underwent postoperative MR imaging at intervals ranging from 8 months to 10 years postoperatively. No patient has been lost to follow-up review and there were no deaths. No patient showed definite clinical or radiological evidence of tumor recurrence during the follow-up period. Recent neurological evaluation revealed functional improvement from initial preoperative clinical status in eight patients, no significant change in 12 patients, and deterioration in three patients. The data support the belief that long-term disease-free control of intramedullary spinal ependymomas with acceptable morbidity may be achieved utilizing microsurgical removal alone. PMID- 2319310 TI - The resurrection of vestibular neurectomy: a 10-year experience with 115 cases. AB - Between 1925 and 1945, Walter Dandy and Kenneth McKenzie performed more than 700 posterior fossa eighth nerve sections and vestibular neurectomies to treat the intractable vertigo accompanying Meniere's disease. During the past 10 years, with the aid of microsurgical techniques and the approach to the posterior fossa through the temporal bone, vestibular neurectomy has undergone a resurgence of popularity. When hearing is to be preserved, vestibular neurectomy is the surgical treatment of choice for patients who fail to undergo a remission of the vertigo attacks of Meniere's disease. This report reviews 115 consecutive vestibular neurectomies performed from 1978 to 1988 for the treatment of Meniere's disease. In 1978, retrolabyrinthine vestibular neurectomy (RVN), a procedure in which the posterior fossa is entered anterior to the sigmoid sinus and behind the labyrinth, was introduced. During the last 3 years, the approach to the posterior fossa has been a small dural opening behind the sigmoid sinus; this approach is known as the combined retrolabyrinthine retrosigmoid approach. There have been no cases of facial paralysis and no serious complications connected with this technique. A high incidence of headache (50%) resulted when the posterior wall of the internal auditory canal was drilled away for better exposure. Transient cerebrospinal fluid (CSF) leaking occurred in 7% of the patients undergoing RVN; however, no CSF leaks occurred when the combined retrolabyrinthine retrosigmoid approach was used. In the RVN series, wound infection occurred in 20% of the cases until perioperative antibiotics reduced the rate to 3%. The results in terms of curing or improving vertigo have been excellent (94%), and hearing has been preserved to within 20 dB preoperative levels in 76% of the cases. Until a cure for Meniere's disease is found, microsurgical posterior fossa vestibular neurectomy remains the best treatment. PMID- 2319311 TI - Retrograde thrombosis of feeding arteries after removal of arteriovenous malformations. AB - Five cases of retrograde thrombosis of former feeding arteries after removal of an arteriovenous malformation (AVM) are reported. The clinical features of these patients were studied and compared to those of 71 patients without this complication. The following characteristics were found to correlate with retrograde thrombosis: 1) advancing age of the patient; 2) large AVM size; and 3) markedly dilated and elongated feeders. It is suggested that the slow flow in the former feeding arteries that was observed immediately after AVM removal and pathological changes in these vessels due to long-standing hemodynamic stresses contributed to the development of retrograde thrombosis. Neurological manifestations related to retrograde thrombosis were noted in three of the five cases. Although infrequent, this complication should be considered as a serious possibility following removal of an AVM. PMID- 2319312 TI - Percutaneous microcompression of the gasserian ganglion for trigeminal neuralgia. AB - The authors report 144 cases of trigeminal neuralgia treated by percutaneous microcompression of the trigeminal ganglion (PMTG). The operation was performed under short-lasting barbiturate anesthesia without endotracheal intubation. Meckel's cave was cannulated with a No. 4 Fogarty catheter and the balloon was inflated for 1 minute. The average intraluminal pressure required for adequate compression of the ganglion was about 1200 mm Hg. All patients were initially relieved of their neuralgia. In a follow-up period ranging from 6 months to 4 1/2 years, 14 patients (9.7%) developed recurrence of pain between 10 and 35 months after surgery. Eleven patients underwent a second PMTG. All nine early failures and 10 of the 11 late recurrences occurred in cases with technical deficiencies. Most of the minor surgical complications observed were also related to avoidable technical errors. There were no anesthetic complications and no deaths. All patients developed mild to moderate postoperative hemifacial numbness with or without objective hypesthesia. Both subjective and objective deficits gradually diminished with time and were well tolerated. One year after the operation nearly 40% of the patients still had patches of slightly decreased sensation in one or more trigeminal divisions and 16% had mild dysesthesia. Anesthesia dolorosa or keratitis was not reported. The PMTG procedure is easy to perform and requires a short operative time and a brief period of hospitalization. It is well tolerated by patients, who describe it as a totally pain-free experience. Morbidity is minimal and recurrence of neuralgia does not seem to be higher than with alternative procedures. PMID- 2319313 TI - Superficial temporal and occipital artery bypass pedicles to superior, anterior inferior, and posterior inferior cerebellar arteries for vertebrobasilar insufficiency. AB - Eighty-three patients underwent 85 intracranial to extracranial pedicle bypass anastomosis procedures to the posterior circulation. There were 15 patients with occipital artery (OA) to posterior inferior cerebellar artery (PICA) anastomosis, 20 patients with OA to anterior inferior cerebellar artery (AICA) anastomosis, and 50 patients with superficial temporal artery (STA) to superior cerebellar artery (SCA) anastomosis. All patients had transient ischemic attacks (TIA's) suggestive of vertebrobasilar ischemia. Twenty-seven patients had crescendo TIA's or stroke in evolution and were considered to be clinically unstable. All patients had severe bilateral distal vertebral artery or basilar artery disease. Twenty-two patients had bilateral vertebral artery occlusion and three had basilar artery occlusion. In this series, 69% had complete resolution of symptoms; the mortality rate was 8.4% and the morbidity rate 13.3%. Clinically stable patients did better than unstable patients. The STA-SCA anastomosis was well tolerated and technically less demanding than the OA-PICA or OA-AICA anastomosis procedures. Patients with symptomatic severe bilateral vertebral or basilar artery disease have a grave prognosis and the option of a surgical arterial pedicle revascularization procedure should be offered to them. PMID- 2319314 TI - Management morbidity and mortality of poor-grade aneurysm patients. AB - Preliminary experience with the occasional good survival of patients in Hunt and Hess Grade IV or V with aneurysmal subarachnoid hemorrhage (SAH) led to a prospective management protocol employed during a 2 1/2-year period. The protocol utilized computerized tomography (CT) scanning to diagnose SAH and to obtain evidence for irreversible brain destruction, consisting of massive cerebral infarction with midline shift or dominant basal ganglia or brain-stem hematoma. These patients, along with those who exhibited poor or absent intracranial filling on CT or angiography, were excluded from active treatment and given supportive care only. All other patients had immediate ventriculostomy placement and, if intracranial pressure (ICP) was controllable (less than or equal to 30 cm H2O without an intracranial clot or less than or equal to 50 cm H2O in the presence of a clot), went on to have craniotomy for aneurysm clipping. Aggressive postoperative hypertensive, hypervolemic, hemodilutional therapy was subsequently employed. Of 54 patients with poor-grade aneurysms, ventriculostomy was placed in 47 (87.0%) and yielded high ICP's in the overwhelming majority, with the mean ICP being 40.2 cm H2O. Nineteen poor-grade aneurysm patients received no surgical treatment and survived a mean of 31.8 hours with 100% mortality. Thirty-five patients underwent placement of a ventriculostomy, craniotomy for aneurysm clipping and intracranial clot evacuation, and postoperative hypertensive, hypervolemic, hemodilutional therapy. The outcome at 3 months of the 35 patients who were selected for active treatment was good in 19 (54.3%), fair in four (11.4%), poor in four (11.4%), and death in eight (22.9%). It is concluded that poor-grade aneurysm patients usually present with intracranial hypertension, even those without an intracranial clot. Based on radiographic rather than neurological criteria, a portion of these patients can be selected for active and successful treatment. Increased ICP can be present without ventriculomegaly, and immediate ventriculostomy should be performed. As long as ICP is controllable, craniotomy and postoperative intensive care can effect a favorable outcome in a significant percentage of these patients. PMID- 2319315 TI - Rupture of aneurysms following balloon embolization. AB - Three cases of complex aneurysms are presented in which balloon embolization therapy was associated with subsequent aneurysmal rupture, causing subarachnoid hemorrhage in two cases and a carotid-cavernous fistula in one. Two of these patients were treated directly by balloon embolization following surgical exploration. The third patient developed the fistula during postembolization volume expansion and heparinization. PMID- 2319316 TI - The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. AB - In a prospective randomized trial designed to study the effectiveness of adjuvant chemotherapy following standard surgical treatment and radiation therapy, 233 eligible patients with medulloblastoma were treated by members of the Children's Cancer Study Group and the Radiation Therapy Oncology Group. Eligible patients were randomly assigned to receive radiation therapy with or without adjuvant chemotherapy consisting of 1-(2-chloroethyl)-3-cyclohexyl-nitrosourea (CCNU), vincristine, and prednisone. The estimated 5-year event-free survival probability was 59% for patients treated with radiation therapy and chemotherapy and 50% for patients treated with radiation therapy alone, a difference which is not statistically significant. The 5-year survival probability was 65% for both groups. Although the treatment difference was not statistically significant when all patients were combined, in the small number of patients with more extensive tumors, event-free survival was better in the group receiving chemotherapy (48% vs. 0%, p = 0.006). In these latter patients the survival time is also significantly prolonged. Extent of disease (as measured by the M staging criteria described by Chang) and age at diagnosis were significantly associated with outcome; advanced disease and young age had a worse prognosis. The extent of tumor resection was not an independent prognostic factor. It is concluded that chemotherapy does not benefit patients with low-stage medulloblastoma, but may benefit those with more advanced stages of disease. PMID- 2319317 TI - Treatment of patients with recurrent gliomas with cyclophosphamide and vincristine. AB - Seventeen patients with recurrent gliomas were treated with the combination of cyclophosphamide and vincristine. All but one had previously received and failed chemotherapy. Cyclophosphamide was administered at doses ranging from 250 to 1000 mg/sq m by intravenous infusion on Days 1 and 2, and vincristine was given at a dose of 1.0 mg/sq m (2 mg maximal dose) intravenously on Day 1; cycles were repeated every 4 weeks. Clinical and radiographic improvement was observed in eight of 16 evaluable patients, and four other patients had stabilization of previously progressive disease. Four patients are alive and off treatment without evidence of recurrence for a median period of 37 months; these included an adult with a cerebral anaplastic astrocytoma now more than 51 months after therapy. Toxicity included moderately severe myelosuppression that required hospitalization in seven patients. These results indicate that the combination of cyclophosphamide and vincristine has activity in the treatment of recurrent gliomas, and warrant the use of these drugs in larger controlled studies, particularly if they can be used in conjunction with hematopoietic growth factors. PMID- 2319318 TI - Invasion of human brain tumors in vitro: relationship to clinical evolution. AB - Embryonic chick heart fragments were confronted in vitro with cells from 26 freshly resected human brain tumors. The tumor-derived cells were scored according to their survival and invasiveness. Four different responses were observed: disintegration of the tumor-derived cells (Type I); survival of cells without progressive engulfing or invasion of the heart fragment (Type II); initial encircling of the heart fragment followed by invasion (Type III); and massive invasion on initial contact (Type IV). Pattern Type III or IV was seen in 11 of 14 preparations derived from malignant tumors, and pattern Type I or II was seen in seven of 10 preparations derived from benign tumors. These results suggested that "classical malignancy," based upon the histological classification and the degree of spread in vivo, correlated with invasiveness in vitro. PMID- 2319319 TI - Neuro-ophthalmological assessment of vision before and after radiation therapy alone for pituitary macroadenomas. AB - Between 1972 and 1988, 25 patients were treated by radiation therapy (RT) alone for pituitary macroadenomas causing visual impairment. Twenty-three patients were evaluated by a neuro-ophthalmologist before treatment and at the time of follow up review. Radiation treatment consisted of 4000 to 5000 cGy over 4 to 5 weeks. The median follow-up period was 36 months (range 2 to 192 months). Eighteen patients (78%) experienced visual field improvement. Deterioration occurred in four patients due to tumor recurrence, tumor hemorrhage, possible optic nerve necrosis, and optic chiasm herniation. Visual field improvement occurred predominantly in patients whose pretreatment visual field defects were less than a dense hemianopsia, who did not have diffuse optic atrophy, and who were younger than the median age of 69 years (p less than 0.001). Visual acuity improvement occurred in patients without diffuse optic atrophy, with only mild impairment of the visual acuity, and with only mild visual field loss prior to RT (p less than 0.002). It is concluded that there is a subset of patients with pituitary macroadenomas and visual impairment for whom primary RT is a treatment option. PMID- 2319320 TI - Somatosensory evoked potentials and neurological grades as predictors of outcome in acute spinal cord injury. AB - An analysis of Motor Index score, pinprick sensory score, joint position sense score, somatosensory evoked potential (SSEP) grade in the ulnar (SSEPu) and posterior tibial (SSEPt) regions, and overall SSEP grade (mean SSEPu + t) was conducted in 36 patients with cervical spinal cord injuries to determine the relationship of these scores, both individually and in combination, to functional outcome (as determined using the Barthel Index) at 6 months after injury. The clinical and electrophysiological data were obtained on the same day within 2 weeks after injury. Nineteen patients underwent two SSEP tests 1 week apart within the first 3 weeks following injury in an attempt to identify mean SSEPu + t improvement. Somatosensory evoked potential grading was based on the presence or absence of the cortical evoked potential, the amplitude of the early cortically generated waveform (P22 or P37), and the interpeak latency across the lesion site. Mean SSEPu + t had the strongest individual relationship with outcome (R-square 0.75, p less than 0.0001) and mean SSEPu + t improvement over a 1-week interval during the first 3 weeks after injury was associated with Motor Index score improvement over a 6 month period. Joint position sense score was the best clinical predictor of outcome (R-square 0.64, p less than 0.0001). Mean SSEPu + t correlated with outcome more closely than the combination of Motor Index score and pinprick sensory score. Mean SSEPu + t in combination with all three clinical indicators produced the strongest correlation with outcome (R square 0.87, p less than 0.0001). This study confirms the prognostic value of quantitative SSEP analysis for patients with acute spinal cord injuries. PMID- 2319321 TI - The significance of morphological changes in cerebral arteries after subarachnoid hemorrhage. AB - A porcine model was developed to allow quantitative assessment of morphological changes in cerebral arteries after subarachnoid hemorrhage and to determine the significance of structural changes in producing arterial narrowing. Whole blood was selectively applied to the middle cerebral artery (MCA) of seven pigs. After 10 days, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. The MCA's exposed to whole blood for 10 days showed prominent luminal narrowing associated with profound ultrastructural changes affecting all layers of the vessel wall. Morphometric analysis, however, demonstrated that significant reductions in the luminal cross sectional area (-55.8% +/- 12.5%, p less than 0.005) and increases in radial wall thickness (75.1% +/- 10.5%, p less than 0.005) were associated with only minimal increase in the cross-sectional area of the vessel wall (12.5% +/- 15%, p less than 0.025). By stereological analysis, the volume density of individual components of the arterial wall was unchanged in MCA's exposed to blood. Vessels exposed to blood showed a 44% reduction in smooth-muscle cell immunoreactive actin and increased collagen in the extracellular matrix of the vessel wall. These data suggest that structural changes in cerebral arteries after subarachnoid hemorrhage do not directly contribute to vessel narrowing through increases in wall mass. Nevertheless, such changes may reflect pathological mechanisms which act to augment prolonged vasoconstriction or inhibit the maintenance of normal vascular tone. PMID- 2319322 TI - The role of hemoglobin in arterial narrowing after subarachnoid hemorrhage. AB - A porcine model for subarachnoid hemorrhage has been developed to allow the selective application of blood and its components to cerebral arteries. Whole blood was centrifuged to produce two fractions consisting of washed erythrocytes (red blood cells, RBC's) and white blood cells (WBC) plus platelet-rich plasma (PRP); the RBC fraction was subsequently separated into hemoglobin (Hb) containing cytosol and erythrocyte membranes. Each fraction was selectively applied to the middle cerebral artery (MCA) of pigs for 10 days; after which, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemical studies. By morphometric analysis, a marked reduction in the MCA lumen cross-sectional area was observed after selective application of RBC's or Hb/cytosol but not of WBC/PRP or erythrocyte membranes. In both RBC- and Hb/cytosol-treated vessels, luminal narrowing was associated with a differential increase in vessel wall thickness of the ventral (subarachnoid) compared to the dorsal (brain) aspect of the artery, but no significant change in cross-sectional area of the vessel wall. After 10 days of exposure to RBC's or Hb/cytosol, there was a spectrum of ultrastructural changes in the vessel wall comparable to those seen after periadventitial application of whole blood. Selective application of commercially available Hb to MCA produced similar structural and morphometric changes. The degree of luminal narrowing after exposure to whole blood or RBC's was proportional to the volume of the erythrocyte mass adjacent to the vessel at sacrifice. These data suggest that arterial narrowing after SAH is mediated by mechanisms related to prolonged exposure of the vessel wall to hemoglobin or its catabolites from lysing subarachnoid erythrocytes. PMID- 2319323 TI - Epidermal growth factor receptors on ependymomas and other brain tumors. AB - Epidermal growth factor receptor (EGFR) and transferrin receptor levels were determined in 14 intracranial neoplasms (four glioblastomas multiforme, four medulloblastomas, four ependymomas, one cerebellar astrocytoma, and one acoustic neurinoma) and in four samples of "normal" brain tissue. A competitive radioreceptor assay with 125I-epidermal growth factor and 125I-transferrin was performed using the primitive neuroectodermal tumor-derived TE-671 tissue-culture cell line as a standard. Epidermal growth factor receptors were present on TE-671 cells, all four ependymomas, and two of the four glioblastomas multiforme. The number of EGFR's per cell for ependymomas were estimated to range from 1000 to 6000. Transferrin receptors were detected on TE-671 cells, two of the four medulloblastomas, and one of the four glioblastomas multiforme. A cell surface binding assay, performed directly on the rat ependymal cell monolayer, was also analyzed. The identification of EGFR's on ependymomas and TR's on medulloblastomas suggests that malignant central nervous system tumors that spread by cerebrospinal fluid pathways may be treatable by intrathecal antibody toxin conjugates. The presence of EGFR's on all of the ependymomas may reflect a role of the receptor in the malignant phenotype of this tumor. PMID- 2319324 TI - Thalamic cavernous malformation. Case report. AB - A 50-year-old man with a right hemiparesis was found to have a cavernous malformation in the left thalamus. The diagnosis was made using magnetic resonance (MR) imaging. The vascular malformation was totally removed by means of a transcallosal interhemispheric surgical approach, but the patient's neurological deficit worsened. The role of MR imaging in establishing the diagnosis is emphasized and other published cases with thalamic locations are reviewed. PMID- 2319325 TI - Dorsal midbrain encephalitis caused by Propionibacterium acnes. Report of two cases. AB - A syndrome of dorsal midbrain dysfunction in association with a central nervous system anaerobic diphtheroid infection is described. Two cases of infection with Propionibacterium acnes manifested as shunt malfunctions with a clinical dorsal midbrain syndrome. Magnetic resonance images showed increased signal in the midbrain tectum which has decreased slowly over time. The evidence suggesting that this syndrome represents bacterial midbrain encephalitis is discussed. PMID- 2319326 TI - Clivus epidural hematoma. Case report. AB - A rare case of epidural hematoma of the clivus is reported in an 11-year-old girl involved in a traffic accident which caused a severe hyperextension injury. Only one similar case has been reported in the literature. The mechanism for the formation of the hematoma of this region is discussed. PMID- 2319327 TI - Intradural granulocytic sarcoma presenting as a lumbar radiculopathy. Case report. AB - Granulocytic sarcoma usually occurs in the setting of leukemia and myeloproliferative disorders. Rarely, it can occur in isolation at various anatomical sites without hematological evidence of leukemia. The unique case of an elderly man presenting with right L2-3 radiculopathy is described. Intradural granulocytic sarcoma of the L-2 and L-3 nerve roots with extradural extension was found at surgery and he was treated with incomplete resection and antileukemic chemotherapy. Local recurrence at 3 months was treated with irradiation. Granulocytic sarcoma is frequently misdiagnosed and invariably progresses to acute leukemia. The chloroacetic acid esterase, granulocytic immunohistochemical markers, and electron microscopy appearance can aid in diagnosis. The prognosis is improved with initial aggressive antileukemic chemotherapy and local irradiation. PMID- 2319328 TI - Microvascular decompression. PMID- 2319329 TI - Creatine kinase BB isoenzyme activity and severe head injury. PMID- 2319330 TI - Low molecular weight peptide inhibitors of medullasin: purification and structure. AB - Two low molecular weight peptide inhibitors of medullasin were isolated from human bone marrow cells. Determination of their amino acid composition and amino acid sequence revealed that one inhibitor was composed of 36 amino acid residues and the other 34 amino acid residues which are identical with the C-terminal portions (Formula; see text) of the beta-chain of human hemoglobin. These two peptides when synthesized also showed the same degree of inhibitory effect on medullasin activity as the natural products. Neither the N-terminal portion of the inhibitor, composed of 21 amino residues, nor the C-terminal peptide, composed of 20 amino acids, inhibited medullasin activity. Medullasin was inhibited reversibly and non-competitively against by these inhibitors and was the most effectively inhibited serine protease among several tested. PMID- 2319331 TI - Effect of N-ethylmaleimide on beef and rat liver vitamin K1 epoxide reductase. AB - There is little difference in the extent of inactivation of beef liver microsomal vitamin K1 epoxide reductase by N-ethylmaleimide (NEM) whether or not the microsomes are pre-treated with dithiothreitol (DTT). The rat liver microsomal enzyme, however, is inactivated by NEM to a much greater extent if the microsomes are pre-treated with DTT. The beef liver enzyme activity is protected from NEM inactivation by the substrate, vitamin K1 epoxide. Ping-pong kinetics are exhibited by the beef liver enzyme. These results support a mechanism for vitamin K1 epoxide reductase in which the function of the required dithiol is to reduce an active site disulfide bond; however, the geometry of the active sites of the enzyme from rat and beef may be different. PMID- 2319332 TI - Further evidence for an essential histidyl residue at the active site of pig liver 5-aminolevulinic acid dehydratase. AB - Photoxidation with methylene blue and rose bengal and chemical modification by diethylpryrocarbonate of pig liver 5-aminolevulinic acid dehydratase produced strong inactivation of the enzyme which was concentration dependent. Loss of enzyme activity by both photoxidation and ethoxyformylation was pH and time dependent and protected by the presence of the substate and competitive inhibitors. The rate of inactivation was directly related to the state of protonation of histidyl groups, the unprotonated from being modified at a much faster rate than the protonated form. Plots of the pseudo-first order rate constants for 5-aminolevulinic acid dehydratase inactivation against pH resulted in typical titration curves showing inflection points at about pH 6.4 for methylene blue and rose bengal and 6.8 for diethylprocarbonate providing further and unequivocal evidence for the existence of critical histidyl groups at the active centre of the enzyme. PMID- 2319333 TI - Photodynamic and non-photodynamic action of several porphyrins on the activity of some heme-enzymes. AB - The action of porphyrins, uroporphyrin I and III (URO I and URO III), pentacarboxylic porphyrin I (PENTA I), coproporphyrin I and III (COPRO I and COPRO III), protoporphyrin IX (PROTO IX) and mesoporphyrin (MESO), on the activity of human erythrocytes delta-aminolevulinic acid dehydratase, porphobilinogenase, deaminase and uroporphyrinogen decarboxylase in the dark and under UV light was investigated. Both photoinactivation and light-independent inactivation was found in all four enzymes using URO I as sensitizer. URO III had a similar action as URO I on porphobilinogenase and deaminase and PROTO IX exerted equal effect as URO I on delta-aminolevulinic acid dehydratase and uroporphyrinogen decarboxylase. Photodynamic efficiency of the porphyrins was dependent on their molecular structure. Selective photodecomposition of enzymes by URO I, greater specificity of tumor uptake by URO I and enhanced porphyrin synthesis by tumors from delta-aminolevulic acid, with predominant formation of URO I, underline the possibility of using URO I in detection of malignant cells and photodynamic therapy. PMID- 2319334 TI - Direct evidence for the cell surface location of a protease-inhibitor complex on intact leukaemia cells. AB - The interaction of a protease with two fluorescent inhibitors has been studied using intact fixed leukaemia cells as the source of the membrane bound enzyme. Fresh rat leukaemia cells were disrupted and the cytosol collected; this extract was known to contain a protein inhibitor of guanidinobenzoatase (GB) associated with leukaemia cells. All the cytosolic proteins were derivatised with Texas red acid chloride. Leukaemia cells with latent GB failed to bind the Texas red inhibitor protein but did so after activation of GB. Competition experiments with 9-amino acridine (a fluorescent marker for the active site of GB) demonstrated that the Texas red-inhibitor protein could only bind to intact leukaemia cells when the active centre of GB was not already occupied by 9-amino acridine. This competition between these two fluorescent inhibitors demonstrated their specificity for GB. The use of intact leukaemia cells and the high molecular weight of the inhibitor protein precludes the possibility of any interaction between GB and inhibitor within the cells. It is concluded that GB and the GB inhibitor complex of latent GB are located on the external surface of intact leukaemia cells. PMID- 2319335 TI - Triplets with conjoined twins. A Nigerian midwife's case report. AB - This article is a case report of a spontaneous vaginal delivery of live triplets, which included conjoined twins joined at the buttocks. The birth was conducted by an experienced midwife in a rural maternity in the Anambra State of Nigeria. The case illustrates the difficulties faced by rural Nigerian midwives when patients need referral to larger hospitals. There is a scarcity of diagnostic equipment, medical back-up, and the transportation that could facilitate an effective referral network. In addition, patients are reluctant to leave their home villages to give birth in a far-away hospital. For these reasons, many difficult births take place in rural maternity centers. The successful outcome of this high risk delivery demonstrates the skill of the local Nigerian midwife, who is frequently faced with unusual complications of childbirth, ones that she must resolve herself. PMID- 2319336 TI - Raising our HIV consciousness. PMID- 2319337 TI - Women's health, women's rights. Should ACNM take a stand? PMID- 2319338 TI - Prenatal cocaine use. Effects on perinatal outcome. AB - Use of cocaine during pregnancy has been associated with increased perinatal morbidity and mortality. It is known to interfere with both physical and psychosocial development of the neonate. This article explores the pathology of cocaine use in pregnancy, its effect on neonatal development, and the role of the nurse-midwife in the perinatal setting. PMID- 2319339 TI - Alcohol and pregnancy. AB - This article summarizes the pathology, incidence, and significance of alcohol related birth defects. Results of a qualitative study that explored reasons why women chose to drink alcohol or to not drink alcohol during pregnancy are presented. Implications for the OB/GYN practitioner and for further research are discussed. PMID- 2319340 TI - The effects of malpractice insurance on certified nurse-midwives. The case of rural Arizona. AB - This study of CNMs in rural Arizona indicated malpractice insurance has had a negative effect on the practice of nurse-midwifery. In 1987 a telephone survey was conducted to assess the effects on the practice patterns of Arizona's 21 rural CNMs, four of whom had had previous experience as licensed midwives. Results indicated 24% had been refused medical back-up by a physician. Although 10% were personally responsible for paying malpractice insurance premiums, they were not able to afford the cost and were going "bare." Nearly 30% had changed their employment status from private practitioner to salaried employee, suffering a decrease in professional autonomy, flexibility of hours, quality of lifestyle, benefits, and income. Unless there are changes that result in lower malpractice insurance premiums or greater compensation and benefits, there likely will be a diminishing number of entries into an increasingly stressed profession. PMID- 2319341 TI - Cholesterol metabolism in adult baboons is influenced by infant diet. AB - We tested the hypothesis that preweaning diet alters cholesterol metabolism in adult baboons. Eighty baboons, progeny of 6 sires and 80 dams, were either breast fed or fed one of three infant formulas containing 2, 30 or 60 mg cholesterol/100 mL. At 16 wk of age the baboons were weaned to one of four diets containing 1.0 or 0.01 mg cholesterol/kcal with 40% of energy from saturated [polyunsaturated fat/saturated fat [P/S) = 0.37] or unsaturated fat [P/S = 2.1] and maintained on these diets until they were necropsied as young adults at 7-8 yr of age. We observed no significant effects of formula cholesterol content on serum lipid or lipoprotein concentrations measured at 6-8 yr of age, but formula cholesterol intake influenced the cholesterol turnover rate and several variables of cholesterol metabolism in the adult. At 6-8 yr, baboons that were breast-fed during infancy, compared with those that were formula-fed, had lower high-density lipoprotein cholesterol (HDL-C) concentrations and higher ratios of very-low density plus low-density lipoprotein cholesterol (VLDL + LDL-C) to HDL-C. Breast fed baboons, as adults, had lower cholesterol production rates, masses of the rapidly exchanging cholesterol compartment (pool A) and neutral steroid excretion rates than did those fed formula as infants. Breast and formula feeding differentially influenced the adult metabolic responses to dietary cholesterol or fat saturation. These results demonstrate that breast vs. formula feeding in infancy alters cholesterol metabolism and serum lipoprotein concentrations in adult baboons. PMID- 2319342 TI - Effect of casein and beta-casomorphins on gastrointestinal motility in rats. AB - The effect of bovine casein and synthetic beta-casomorphins on the motility of rat gastrointestinal tract was studied by noninvasive techniques using the nonabsorbable marker 141Ce. Casein suspensions (CAS) or whey protein suspensions (WPS) were labeled with 141Ce and fed by gastric tube. Gastric emptying rate (GER) as well as gastrointestinal transit time (GITT) of the tracer were significantly longer with feeding CAS compared to WPS. The differences between the CAS and the WPS groups were partly (GER) or completely (GITT) abolished by pretreating the animals with the specific opiate-receptor antagonist naloxone. It is assumed that opioid peptides released from casein during digestion slowed gastrointestinal motility by direct interaction with gut opiate receptors. To prove whether beta-casomorphins, when given by gastric tube, can affect motility, different synthetic beta-casomorphins in doses between 1 and 10 mg were added to the WPS. The beta-casomorphin-4 (Tyr-Pro-Phe-Pro-NH2) showed no effect on GITT. The D-Ala substituted D-Ala-beta-casomorphin-4 (Tyr-D-Ala-Phe-Pro-NH2) and D-Ala beta-casomorphin-5 (Tyr-D-Ala-Phe-D-Ala-Tyr-NH2), which are more resistant to proteolytic attack and have higher opioid potency than beta-casomorphin-4, slowed GITT in a dose-dependent manner. PMID- 2319343 TI - In vivo evidence for a vitamin B-6 requirement in carnitine synthesis. AB - The purpose of this study was to determine whether there is a requirement for vitamin B-6 (B6) in carnitine synthesis. Rats were fed a B6-deficient (-B6) (0.04 mg pyridoxine [PN]/kg) diet (ad libitum or meal-fed) or a control (+B6) (5.7 mg PN/kg) diet (ad libitum or pair-fed). These diets were fed for 6 wk, then some of the rats were repleted with the +B6 diet for 2 wk. Total acid-soluble carnitine (TCN) and free carnitine (FCN) levels were compared in the plasma, liver, skeletal muscle, heart muscle and urine and rats fed +B6 or -B6 diets. In -B6 rats vs. +B6 rats, TCN levels were significantly lower (P less than 0.05) in the plasma, skeletal muscle, heart muscle and urine, but not in the liver. However, if rats were fasted for 3 d, liver TCN concentration of -B6 rats was significantly lower than that of +B6 rats. After B6-deficient rats were repleted with the +B6 diet, the TCN level in the plasma, liver, skeletal muscle, heart muscle and urine returned to the levels of control rats. Thus, the decrease in TCN and FCN levels with a B6-deficient diet and the increase of these levels after B6 repletion provides evidence for the B6 requirement in the biosynthesis of carnitine. PMID- 2319344 TI - Calcium and magnesium utilization in rats: effect of dietary butterfat and calcium and of age. AB - This factorial study was designed to examine the effect of short- and long-term ingestion of dietary calcium (0.25% and 1.0%) and butterfat (5% and 20%) and treatment with dimethylhydrazine (DMH) in rats. Calcium, magnesium and phosphorus absorption and, to a lesser extent, total diet digestibility decreased as the rats aged from 2 to 8 mo. Increased ingestion of butterfat had no effect on apparent absorption of calcium among young rats but tended to decrease calcium absorption in mature rats. The weak effect (P less than 0.05) of butterfat on calcium absorption reflected the small amount of calcium (less than 2% of fecal calcium) associated with lipids in feces. Ingestion of 10 vs. 2.5 mg Ca/g diet reduced the efficiency of apparent absorption of calcium, magnesium and phosphorus of young and mature rats and resulted in slightly, but significantly, greater retention of calcium in bone after 27 wk. The total amounts of calcium retained in tibias were correlated with the amounts of calcium absorbed by rats after 4, but not after 27, wk of dietary treatments. Rats dosed with DMH exhibited improved efficiency of calcium absorption, but the incidence of intestinal tumors did not affect mineral utilization. PMID- 2319345 TI - Effect of chronic selenite supplementation on selenium excretion and organ accumulation in rats. AB - We examined the effect of chronic selenite supplementation on whole body and selected organ selenium (Se) accumulation, urine excretion of total Se and trimethylselenonium ion, and Se balance in adult male rats. Animals were housed in metabolic cages and given either deionized water or water containing 4 micrograms of Se/mL as selenite for 30 d. Absorption of selenite was nearly complete, with only approximately 10% of ingested Se appearing in feces. There was a rapid rise in urinary Se that reached a plateau within a few days and accounted for 54 +/- 2% of the intake. Excretion of trimethylselenonium ion (TMSe) in urine increased rapidly, representing 35-40% of urinary Se in the supplemented animals compared with only 2% for the control group. In one experiment, rats were killed at 30 d and total carcass Se was measured using isotope dilution analysis. Supplemented rats had only a modest increase in whole body Se (94 +/- 4 micrograms Se vs. 66 +/- 3 in controls). Calculation of Se balance in the supplemented rats showed that approximately 35% of ingested Se could not be accounted for by urine plus fecal losses combined with the portion retained in the carcass. The results from this study demonstrate that under the condition of supplementation at 4 micrograms of Se/mL of drinking water, pathways other than urinary and fecal excretion may account for a substantial portion of Se loss. PMID- 2319346 TI - Effect of dietary iron overload on lipid peroxidation, prostaglandin synthesis and lymphocyte proliferation in young and old rats. AB - The effect of dietary iron overload on lipid peroxidation (LP), prostaglandin (PG) synthesis and lymphocyte proliferation was examined in young and old F344 rats. Rats 4 and 19-22 mo old were fed AIN-76 diet for 11-12 wk supplemented with 2.5% carbonyl iron obtained from two sources (Type A and B). Animals supplemented with Type A iron showed reduced food intake and weight gain associated with marked increases in extrahepatic and hepatic iron concentration. Rats receiving Type B iron had food intakes and body weights similar to those of controls but exhibited small increases in tissue iron concentration. Old control rats compared to young had significantly higher conjugated dienes (CD) in hepatic microsomes. Feeding Type A iron diets induced a significantly higher level of CD in hepatic microsomes from old rats compared to young rats. Iron overloaded rats also showed highly correlated (r = 0.94) increases in the urinary excretion of thiobarbituric acid-reactive substances and PG metabolites indicating increased in vivo LP and PG synthesis. Mitogen-stimulated PGE2 synthesis in young rats was increased at 4 wk in association with enhanced T-cell proliferation stimulated by Concanavalin A. Lymphocyte proliferation was significantly lower in old than in young control or iron-treated rats. The lack of efficacy of Type B vs. Type A iron appears due to a larger particle size and lower bioavailability. In conclusion, iron overloading increases in vivo LP and PG metabolism. Furthermore, the mitogenic response to Concanavalin A in young rats is enhanced after 4 wk of iron overloading. PMID- 2319347 TI - Coenzyme A metabolism in vitamin B-12-deficient rats. AB - Vitamin B-12 (cobalamin) deficiency results in decreased L-methylmalonyl-coenzyme A (CoA) mutase activity. The consequence of this defect on the cellular CoA pool was studied in rats with functional vitamin B-12 deficiency induced by administration of the cobalamin analogue hydroxy-cobalamin [c-lactam] or by dietary vitamin B-12 deficiency. Both types of vitamin B-12 deficiency were associated with methylmalonic acidemia (100-300-fold increases in plasma methylmalonic acid concentration compared with controls), but overall fuel homeostasis was intact. Liver from rats treated with hydroxy-cobalamin [c-lactam] contained a threefold greater concentration of total CoA (free CoA plus all acyl CoA) compared with saline-treated rats. Fractionation of the CoA pool revealed higher levels of CoA, propionyl-CoA, methyl-malonyl-CoA, acid-insoluble CoA, as well as total CoA in the rats treated with hydroxy-cobalamin [c-lactam] compared with controls. Similar increases in liver CoA content were seen in dietary vitamin B-12 deficiency in both the fed and fasted states. To examine the hypothesis that sequestration of hepatic CoA as propionyl-CoA and methylmalonyl CoA could increase CoA biosynthesis, the effect of propionate on CoA biosynthesis was studied in hepatocytes isolated from control rats. Propionate (1 mM) increased the formation of 14C-CoA from [14C]pantothenate (10 microM) by 27% in the hepatocyte system. When butyrate (1 mM) was provided as substrate, propionate (10 mM) increased [14C]CoA formation by 63%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319348 TI - Food intake and choice in lean and obese Zucker rats after intragastric carbohydrate preloads. AB - Feeding behavior in response to a carbohydrate preload was determined in lean and obese Zucker rats. Rats were adapted to a schedule of feeding during a 12-h daily dark period. Carbohydrate preloads (cornstarch in water) were given by intragastric intubation 30 min before rats had access to a choice of two diets that differed in their protein and carbohydrate contents. Behavioral responses of lean rats to carbohydrate preloads were prompt and selective. In the first hour of feeding, reduction in intake, mainly of the high carbohydrate-low protein diet, more than compensated for the energy content of the preload. In contrast, obese rats failed to achieve a similar degree of compensation to the energy surplus from the carbohydrate preload during the first hour of feeding. Also, their decreases in food intake were nonselective. In general, it took obese rats two or more hours to adjust their feeding behavior in response to a carbohydrate preload. Increasing the size of the preload did not improve the overall response of obese rats, but an extra 30-min lapse between preload and food access led to selective suppression in first-hour intake from the high carbohydrate-low protein diet. These findings suggest that altered food intake and selection behavior of the obese Zucker rat may be, in part, due to a delay in response to physiologic and metabolic changes arising from carbohydrate ingestion. PMID- 2319350 TI - The battle against smoking. PMID- 2319349 TI - Active vs. passive agents: implications for dietary recommendations. PMID- 2319351 TI - Retirement self-efficacy: the effects of socioeconomic status, life satisfaction, health, and readiness for retirement. AB - The purpose of this study is to determine if educational level, occupation, socioeconomic status, life satisfaction, self-rated health, and readiness for retirement are correlated with retirement self-efficacy (RSE). Second, this study investigates whether the combination of these variables gives a better explanation of RSE than does any variable singly. Eight-three retired and 40 pre retired subjects participated in this study. RSE was measured by the Retirement Self-Efficacy Scale. Higher education, occupational class, socioeconomic level, and readiness for retirement were all found to be positively related to RSE (p less than .05) for the total group. The strongest predictors of RSE were readiness for retirement for the retired group (p less than .05) and life satisfaction for the pre-retired group (p less than .01). PMID- 2319352 TI - The address of the President of the New York State Nurses Association. PMID- 2319353 TI - The relationship of burnout, use of coping strategies and curricular program of registered nurses. AB - This study examined the relationships of nursing curricular program, burnout, and use of coping strategies among 150 randomly selected staff nurses from four hospitals. The instruments used were the frequency dimension of the Maslach Burnout Inventory (Maslach & Jackson, 1981) and the Ways of Coping (Revised) (Folkman & Lazarus, 1985). Discriminant analysis demonstrated that (a) diploma graduates differed from associate-degree graduates in their greater experience of Emotional Exhaustion (p less than .05) and (b) baccalaureate-degree graduates differed from associate-degree graduates in their greater use of Planful Problem Solving and Confronting Coping (p less than .05). Recommendations include additional research to discover relevant factors for the greater experience of Emotional Exhaustion among diploma graduates. If related to perceptions of limited career mobility due to the lack of a baccalaureate degree, expansion of educational opportunities is indicated. Another recommendation is curricular incorporation of content on burnout and coping. PMID- 2319354 TI - Nurses' perceptions of co-worker responses to smoking cessation attempts. AB - A descriptive research design was used to answer the following question: What is the nature of nurses' perceptions of their co-workers' responses to quit attempts, among nurses who have experienced relapse in smoking cessation? A questionnaire measuring two discrete responses to quit attempts, namely co-worker support and co-worker discouragement (Sorensen, Pechacek, & Pallonen, 1986), was mailed to 5,418 registered nurses in the New York area. The response rate was 45%. Relapsers perceived that they received significantly more (p less than .001) co-worker support than co-worker discouragement during quit attempts. Nevertheless co-worker support occurred infrequently. Many smokers may have received no response from their co-workers. Further efforts to help nurses quit smoking may need to emphasize strategies for enhancing social support. PMID- 2319355 TI - Results of a work-site educational and screening program for hypertension and cancer. AB - Cardiovascular disease and cancer account for 68% of deaths in the United States each year. Office-based screening efforts to detect early or asymptomatic disease have been modestly successful at best, as neither patients nor physicians routinely follow American Cancer Society guidelines. The work site, representing a captive group of patients, is an alternative screening site. Eight hundred eighty-eight employees at 10 work sites were screened for hypertension and six types of cancer (oral, breast, rectal, colon, prostate, and testicular). Fifty one employees with new onset or poorly controlled hypertension were identified, along with two early cancers (rectal, breast) and four malignant precursors. Potential dollar savings to employee, employer, and society were three times the cost of the screening program. Screening at the work site represents an efficient, cost-effective approach for the early detection of hypertension and cancer. PMID- 2319356 TI - Absence of adverse mortality effects in workers exposed to methylene chloride: an update. AB - Mortality findings in a 1964 to 1970 cohort of 1013 hourly-wage men exposed to methylene chloride were substantially unchanged after 4 additional years of observation through 1988. Mean exposure was 26 ppm (8-hour time-weighted average) for 23 years; median follow-up from first exposure was 33 years. A comparison with death rates in both general population and industrial referents showed nonsignificant deficits in observed-expected ratios for such hypothesized causes as lung and liver cancer and ischemic heart disease. Overall mortality from 1964 to 1988 (n = 238) was significantly decreased v both referent groups. The study had 90% power to detect relative risks of 1.7 and 1.3 for lung cancer and ischemic heart disease, respectively; power was inadequate for hepatic cancer. No pancreatic cancer deaths occurred since the 1984 follow-up; eight have been observed v 4.2 expected (P = .13). An analysis of dose response for selected causes of death demonstrated no statistically significant trend according to either career methylene chloride exposure or latency. Similar results were observed when the data were analyzed using Poisson regression modeling. PMID- 2319357 TI - Smoking and morbidity frequency in a working population. AB - As part of Shell's health surveillance program, morbidity frequency and severity by smoking status (current smoker, exsmoker, nonsmoker) were compared for the 3 year period 1985 through 1987. Morbidity data for this study were extracted from the morbidity section of the Shell Health Surveillance System, which included all illness and absence events in excess of 5 days. Statistically significant positive associations were seen between smoking habits and overall morbidity, diseases of the circulatory system, and diseases of the respiratory system for both male and female employees. In addition, a significantly increased association between smoking and both non-motor vehicle accidents and motor vehicle accidents among current smokers was noted. Current smokers had a greater than 60% higher frequency rate (P less than .05) for non-motor vehicle accidents than nonsmokers for both men and women. Male smokers also had a 75% increased (P less than .05) motor vehicle accident rate. These results suggest that it may be possible to reduce overall illness and injury morbidity through implementation of successful smoking cessation programs. PMID- 2319358 TI - Bias on withdrawing lost subjects from the analysis at the time of loss, in cohort mortality studies, and in follow-up methods. AB - Cohort mortality studies may differ from morbidity and other follow-up studies in that, in many of the methods of follow-up employed, the identification or follow up process and the process of determination of outcome (death) are essentially the same. Furthermore, some of the methods may involve preferential identification of deaths over live persons, or vice versa. This latter area of difference is particularly problematic in situations in which the comparison group (the general population) has not been subjected to tracing, and in which certain persons who are being traced are not covered by the universe defined by the follow-up method. Because of these peculiarities, it is shown that, during the analysis, the usual practice of withdrawing persons lost to follow-up at the time of loss can lead to seriously biased results when follow-up rate is not very high. PMID- 2319359 TI - A model system for occupational disease surveillance activities applying Centers for Disease Control guidelines to poison control centers. AB - Each year, poison control centers (PCCs) receive more than 25,000 calls related to workplace exposures to hazardous substances. Recent studies indicate that each caller may be a sentinel contact representing other exposed or ill workers. Although PCCs traditionally focus their follow-up efforts on the treatment of the index case alone, with minimal attention to the public health implications of other exposed or ill workers, PCCs could serve as a national surveillance system for occupational illnesses, a system with both passive and active attributes. PMID- 2319360 TI - Nonauditory injury threshold for repeated intense freefield impulse noise. AB - Exposure to impulse noise is an important occupational health concern. The risk of injury to auditory structures is well recognized and provides the cornerstone for present safety standards. For freefield impulse noise, nonauditory injury is dependent on peak pressure, positive phase duration (or impulse), and number of exposures. Trivial laryngeal petechiae are shown to precede nonauditory injury to more critical organs (ie, pulmonary and gastrointestinal systems). This study identifies the critical impulse noise thresholds causing trivial laryngeal petechial changes resulting from exposure to 5, 25, and 100 repetitions of specific levels of impulse noise. Because of anatomical differences, sheep should be slightly more susceptible to impulse noise laryngeal petechial changes than man; therefore, it seems reasonable to set the absolute limits for human occupational exposure levels below those causing laryngeal petechiae in sheep for persons wearing adequate hearing protection. This study does not address human auditory injury that may occur above or below these exposure limits even with proper hearing protection. PMID- 2319361 TI - ILO "A" and "B" reader classification. PMID- 2319362 TI - The treatment of preterm labor using a portable subcutaneous terbutaline pump. AB - The perinatal mortality rate related to preterm delivery has led researchers to investigate new methods of tocolysis. A new concept in managing preterm labor uses continuous administration of terbutaline sulfate via a portable subcutaneous infusion pump. Use of the terbutaline pump to treat 13 preterm labor patients at the Baylor College of Medicine demonstrated an efficacy rate of 9 for a population failing all other methods of tocolysis. This unique treatment modality offers new hope for patients experiencing recalcitrant preterm labor. PMID- 2319363 TI - Recognizing the onset of labor. AB - An experimental study compared the use of an educational technique based on patient participation with routine instructions to prepare patients to recognize the onset of active labor. The number of visits to the labor suite that resulted in the patient being discharged undelivered was significantly lower in patients who received the educational intervention. The study revealed that, without any increase in time, nurses can prepare patients to make judgments about the need for hospitalization. PMID- 2319364 TI - The relationship of primigravid sleep experience and select moods on the first postpartum day. AB - Documented studies have indicated that sleep loss occurs in women during the third trimester of pregnancy. This study quantified the third trimester and intrapartal sleep of 28 primigravid women to identify the relationship between sleep loss and the presence of anxiety, hostility, and depression on the first postpartum day. The study sample reported an increase in third-trimester sleep but significant intrapartal sleep loss. A computation of Pearson's correlation coefficient indicated no significant relationship between sleep loss and moods of anxiety, hostility, and depression. PMID- 2319365 TI - Factors related to decisions about infertility treatment. AB - This descriptive study identifies preferences that 147 persons with infertility held about treatment options and the factors they perceived as most important in making decisions about undergoing various treatments. Medical regimens, artificial insemination with husband's sperm, and surgical procedures are identified as the preferred treatments. The most important factors influencing couples' decisions about infertility treatments are personal beliefs, partner's beliefs, physician's advice, and emotional stress. Implications for nurses in the role of decision counselor are suggested. PMID- 2319366 TI - Candidiasis in the breastfeeding mother and infant. AB - Candidiasis in a breastfeeding mother and infant is described. The mother's breasts were a continuous source of Candida albicans, resulting in persistent thrush in the infant. The infant and mother were successfully treated with clotrimazole in a gel form. This report emphasizes the importance of treating both the infected mother and infant to prevent reinfection and ensure successful breastfeeding. PMID- 2319367 TI - Use of cyclosporine in the mouse heterotopic heart transplant model. AB - We refined the mouse ear-heart transplant model developed by Fulmer and coworkers and tested cyclosporine as a sole immunosuppressive agent in this model. Three week-old CBA mice were used as heart recipients, and unsexed newborn BALB/c mice were used as heart donors. The heart grafts were examined for visible pulsations at 10-fold to 20-fold magnification daily for the first 10 days and every other day thereafter. Graft electrocardiograms were also obtained on the same schedule. Preliminary studies had established that a dose of 15 mg/kg/day was the optimal cyclosporine dose in our model. This dose was administered subcutaneously to each of two treatment groups. Group 2 received this dose for the entire 30-day experimental period. Group 3 received this dose for the first 16 days of the experimental period. Group 1 consisted of allografts receiving no immunosuppression. Group 1 grafts showed evidence of initial successful engraftment by day 7; however, by day 13 none of the grafts remained viable. In group 2, 19 of 23 grafts remained viable for the entire experimental period. In group 3, all of the grafts remained viable until day 17 (after day 16 cyclosporine was discontinued) and rapidly lost evidence of viability thereafter. By day 21, none of the grafts in group 3 remained viable. Survival curves for the three groups as determined by electrocardiogram and visible pulsations were constructed, and the differences between the curves were significant (p = 0.001). The results of this study demonstrate the potential usefulness of the ear-heart transplantation model in screening immunosuppressive agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319368 TI - Enhanced 24-hour in vitro heart preservation with adenosine and adenosine monophosphate. AB - Continuous hypothermic perfusion is an effective means of preserving ex vivo cardiac allografts. Using canine hearts, we assessed the ability of the high energy phosphate precursors adenosine and adenosine monophosphate to enhance the protective effect of continuous hypothermic perfusion. Group 1 hearts (controls) were perfused for 24 hours with a modified Krebs-Henseleit solution. Group 2 hearts were perfused with control perfusate to which adenosine was added (20 mumol/L). Group 3 hearts were perfused with control perfusate with adenosine monophosphate (0.1 mmol/L). After perfusion heart weights increased similarly in all groups. Coronary vascular resistance increased during the preservation period in group 1 hearts, but decreased in groups 2 and 3 hearts. Developed pressures were 103 +/- 22 mm Hg in group 1, 163 +/- 27 mm Hg in group 2 (p less than 0.01), and 141 +/- 34 mm Hg (p less than 0.05) in group 3. The rate of pressure development in group 2 (2143 +/- 249 mm Hg) and group 3 (2059 +/- 395 mm Hg) hearts was significantly greater than in group 1 hearts (1434 +/- 363 mm Hg, p less than 0.01). Only group 3 myocardial adenosine triphosphate levels were significantly greater than controls (3.18 +/- 0.52 mumol/gm vs 2.12 +/- 0.74 mumol/gm, p less than 0.05) on completion of perfusion. Myocardial lactate levels at this time were significantly higher in group 1 hearts (7.48 +/- 3.96 mumol/gm) compared with groups 2 and 3 (0.34 +/- 0.58 mumol/gm and 1.50 +/- 0.91 mumol/gm, respectively, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319369 TI - Lack of progressive "restrictive" physiology after heart transplantation despite intervening episodes of allograft rejection: comparison of serial rest and exercise hemodynamics one and two years after transplantation. AB - It has been suggested that the cardiac allograft becomes less compliant either because of repeated episodes of rejection, chronic hypertension, or as a direct consequence of immunosuppression. A corollary to this hypothesis is that this reduction in compliance should be a progressive, rather than a static, change. To test this hypothesis, rest and exercise filling pressures, cardiac outputs, and radionuclide ventriculographic systolic and diastolic indices were measured in 20 patients at 1 and 2 years after heart transplant by means of identical protocols at both study times. Between studies 10 of 20 patients had no rejection, five of 20 had one rejection episode, and five of 20 had more than one rejection episode. There were no significant differences in resting or exercise heart rates, pulmonary wedge pressures, cardiac outputs, left or right ventricular ejection fractions, left ventricular peak filling rates, or time to peak filling between the studies at 1 and 2 years. Only resting right atrial pressure increased between year 1 and year 2 (6 +/- 2 mm Hg vs 8 +/- 4 mm Hg, p = 0.035). These data demonstrate that cardiac allograft function is unchanged between 1 and 2 years after transplantation, despite episodes of intervening rejection and continued immunosuppression. The data further suggest that the previously reported decrease in cardiac allograft compliance does not appear to be caused by a progressive intrinsic abnormality in the allograft, and that other mechanisms for "restrictive" allograft physiology should be sought. PMID- 2319370 TI - Relationship between preoperative pulmonary status and outcome after heart transplantation. AB - To determine whether routine preoperative pulmonary function tests provide useful prognostic information in orthotopic heart transplant candidates, we evaluated the pulmonary status of 33 patients who subsequently underwent transplantation. There was one perioperative death and five other fatalities within 9 months after operation. Mean age of the six patients who died (mean +/- SD 51.8 +/- 5.0 years) was significantly different (p less than 0.05) from that of the survivors (44.6 +/- 11.1 years). Mean preoperative pulmonary vascular resistance was significantly different (p less than 0.05) between those patients who had a fatal outcome (mean, 4.4 +/- 2.0 mm Hg/L/min) and those who survived (2.7 +/- 1.0 mm Hg/L/min). By contrast, we found that measures of forced vital capacity, forced expired volume in 1 second, diffusion capacity for carbon monoxide, and arterial blood gases bore no apparent relationship to outcome. We conclude that standard noninvasive measures of pulmonary function may be useful in preoperative preparation of heart transplant candidates, but they do not appear to be helpful in predicting eventual outcome. PMID- 2319371 TI - Postoperative organic mental syndromes in lung transplant recipients. Toronto Lung Transplant Group. AB - Delirium and other organic mental syndromes have frequently complicated the postoperative course of lung transplant recipients. A retrospective survey of 30 single-lung, double-lung, and heart-lung transplantations was undertaken to investigate the frequency of postoperative delirium, the responsible causative factors, and the efficacy of management strategies. Seventy-three percent of all recipients demonstrated an episode of delirium during their first 2 postoperative weeks. Undergoing cardiopulmonary bypass, having higher cyclosporine levels, and moving one's home from a distant location to await surgery were associated with an increased risk of postoperative delirium. A protocol that uses the intravenous administration of haloperidol has proved both effective and safe in the management of this frequently problematic complication. PMID- 2319372 TI - Cytoimmunologic monitoring after heart and heart-lung transplantation. AB - The ability of cytoimmunologic monitoring to detect acute rejection in heart and heart-lung transplant recipients was assessed. Seventeen heart and nine heart lung transplant patients treated with cyclosporine as the primary immunosuppressive agent were monitored after operation. Seventeen acute rejection episodes occurred in the heart-only recipients and 12 in the combined heart-lung recipients. These acute rejection reactions were accompanied by increased numbers of "activated" lymphocytes in all but one case, providing cytoimmunologic monitoring a sensitivity of 100% in the heart-lung recipients and 94% in the heart recipients. The specificity was, however, low (68% in the heart recipients and 55% in the heart-lung recipients). Seventy-two percent of the false-positive results were associated with viral infections, particularly cytomegalovirus infections. PMID- 2319373 TI - Heart transplantation for intractable prosthetic valve endocarditis. AB - A 25-year-old woman with active systemic lupus erythematosus and infective endocarditis was seen initially with porcine aortic bioprosthetic stenosis, perivalvar regurgitation, and native mitral regurgitation 9 years after aortic valve replacement for lupus endocarditis. Double-valve replacement was performed with St. Jude Medical mechanical prostheses. After operation the patient developed fever and an elevated white blood cell count. One month later she had increasing mitral and aortic perivalvular regurgitation and intermittent complete heart block. At reoperation both annuli showed evidence of continued infection, and she underwent annular reconstructions with pericardium and double-valve re replacement. Cultures grew Mycoplasma hominis. Despite long-term therapy with appropriate antibiotics, within 2 months she developed recurrent perivalvar regurgitation with congestive heart failure. Orthotopic heart transplantation was performed. The postoperative course was notable for significant leukocytosis and spontaneous culture negative hemothorax that required thoracotomy for drainage. The patient recovered and is now well 14 months after operation. PMID- 2319374 TI - Autologous muscle to assist the failing heart: first experiments. AB - This report summarizes early work to explore the harnessing of noncardiac muscle to supplement the work of the failed left ventricle. First experiments, in 1959, investigated the possibility of using the mobilized left diaphragm around the distal portion of the thoracic aorta. A stimulus was delivered to the left phrenic nerve during diastole, causing that portion of the aorta to be collapsed by the contracting muscle and thus act as a pump. A significant rise in diastolic pressure compared with controls was obtained in all experiments. This study and later investigations with a graft sutured to the left ventricle indicated the feasibility and promise of biologic augmentation. The inherent problems of stroke volume and fatiguability of the transposed diaphragmatic muscle, at the repetitive rates required for adequate hemodynamic assistance in the dog, led us to explore other approaches to cardiac assistance. PMID- 2319375 TI - Comparative anatomy and histochemistry of human and canine latissimus dorsi muscle. AB - Gross and histologic studies of human and canine latissimus dorsi muscle were carried out to identify anatomic and histochemical properties that may be relevant to its use as a resource muscle, particularly for heart reconstruction. In both human and canine latissimus dorsi, three distinct muscle segments were observed, differing in direction of fibers, fiber characteristics, thickness, and blood supply. The entire canine latissimus dorsi could also be separated into superficial and deep layers, whereas only the anterolateral segment of human latissimus dorsi was separated further by the neurovascular bundle. Histochemical studies suggested significant differences between the ratios of fast to slow fibers in the superior and anterolateral segments of human muscle. Variation in size, weight, and shape within and between subjects demonstrates a need for careful evaluation of the potential resource muscle. PMID- 2319376 TI - Simple electrical model of the circulation to explore design parameters for a skeletal muscle ventricle. AB - To efficiently investigate a variety of designs for an accessory skeletal muscle ventricle for circulatory assistance, we developed an electrical model of the human circulatory system. Heart and blood vessels were modeled as resistive capacitive networks, pressures as voltages, blood flow as electric current, and the cardiac valves as diodes. Pumping of blood was simulated by the application of damped rectangular voltage pulses to the capacitances of the cardiac ventricles and the skeletal muscle ventricle. Three configurations of a skeletal muscle ventricle were studied: the apico-aortic, in which the skeletal muscle ventricle is interposed between the left ventricle and the abdominal aorta; the aorto-aortic, in which the skeletal muscle ventricle is interposed between the thoracic aorta and the abdominal aorta; and the atrial-aortic, in which the skeletal muscle ventricle is interposed between the left atrium and abdominal aorta. The three skeletal muscle ventricle designs were tested as counterpulsatile assist devices in simulations of the normal circulation and congestive heart failure. Performance of the various skeletal muscle ventricle designs was evaluated by comparing total output, mean left ventricular power expenditure, mean skeletal muscle ventricle power expenditure, and mean perfusion pressure of the skeletal muscle comprising the pouch. Under both normal heart and heart failure conditions, the apico-aortic design was superior to the aorto aortic and to the atrial-aortic designs. With optimal stimulation parameters, the apico-aortic design reduced left ventricular minute work to 16% of normal during simulated heart failure while maintaining a viable resting cardiac output of 3.4 L/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319378 TI - Nursing care of the ambulatory patient with a mechanical assist device. AB - Since 1986, 10 men and one woman were ambulatory while supported with mechanical assist devices as a bridge to heart transplantation. Four patients received a subclavian intraaortic balloon pump, two were supported with a Novacor left ventricular assist system, three patients received Pierce-Donachy ventricular assist devices, and one patient received a Jarvik 7 total artificial heart. One patient with an intraaortic balloon pump later received a left ventricular assist system because of hemodynamic deterioration despite the intraaortic balloon pump. Before device insertion all 11 patients were in cardiogenic shock despite inotropic and vasodilator support. The time of support ranged from 8 to 440 days (median, 24 days). In-house coverage by the circulatory support team was necessary only during the first 24 to 72 hours of support. When the patient's condition was stabilized, nursing staff monitored the devices with "on-call" availability of the circulatory support team. After implant of the device, all patients were able to perform activities of daily living. Once patients were able to walk in their hospital rooms, ambulation began in the hallways; frequency and distance were gradually increased. Four of the patients walked outside the hospital while tethered to the drive console. Daily physical therapy contributed to increased exercise tolerance. Protective isolation was used before and after transplantation to minimize the risk of infection. Sterile dressing changes (gown, gloves, mask) were applied to drive lines, cannula sites, and incisions. All invasive lines and catheters were removed as soon as the patient's clinical condition warranted, and noninvasive monitoring was used to decrease the chance of infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319380 TI - The challenge of rural health care. PMID- 2319379 TI - Dawn in the east. PMID- 2319377 TI - Management of rejection in heart transplant recipients: does moderate rejection always require treatment? AB - Triple-drug immunosuppression with cyclosporine, azathioprine, and steroids was introduced at Papworth Hospital in 1986. The management of rejection episodes in the first 40 patients receiving this regimen was reviewed for a minimal follow-up period of 18 months. Routine endomyocardial biopsy specimens were taken and classified into nil, minimal, mild, moderate, and severe rejection categories. Management was dependent on the biopsy result, in addition to the clinical state of the patient. In the early postoperative period (day 0 to 30) 2% of biopsy results showed severe rejection and 27% showed moderate rejection; all but one of the latter patients received augmentation of immunosuppression. In the intermediate period (days 31 to 90) severe rejection was present in 1% and moderate rejection in 36 (31%) of biopsies. Immunosuppression was augmented in 13 symptomatic patients, but in 23 asymptomatic patients additional therapy was withheld and the biopsy was repeated in 5 to 7 days. If moderate rejection was still present (11 cases), immunosuppression was augmented. Later (3 to 12 months) augmentation of immunosuppression was given on only four occasions. When the histologic criteria for diagnosis of moderate rejection are present during the early period after transplantation, we recommend augmented immunosuppression. In cases of later rejection we suggest that the decision be based on the biopsy result and the clinical condition of the patient; however, a prospective controlled trial will be required to confirm that this policy is correct. PMID- 2319381 TI - Double penetrating nail injury to the eye: a case report. AB - We report an unusual double penetrating eye injury in which a 26 mm carpenter's nail pierced the eye. The nail penetrated the sclera equatorially and pierced the retina posteriorly just above the superior temporal retinal vascular arcade. Six hours following the injury the nail was removed from the eye, trans-scleral cryotherapy was applied to the entry site, and an episcleral silicone band was used to create an encircling buckle. Visual acuity at 2 months and most recently at 33 months following the injury was 20/30. This case demonstrates that selected double penetrating injuries of the posterior segment may be successfully managed with conventional scleral buckling techniques and underscores the importance of protective eye wear for hobby work or leisure activities. PMID- 2319382 TI - Survival of severe neuroleptic malignant syndrome in a 78-year-old man treated with dantrolene. AB - The authors report a case of neuroleptic malignant syndrome in a 78-year-old man. The patient presented with a lack of contact with reality, hallucinations to which he was responding incoherently, and agitation and belligerence. He showed much improvement following treatment with dantrolene and was released to a nursing home 24 days after admission. PMID- 2319383 TI - [Deviation and rotation of the larynx in computer tomography]. AB - Many authors described the clinical importance of asymmetry of the laryngeal framework. However, its pathogenesis is generally unknown. In this study, CT images of 315 Japanese subjects were investigated to define the laryngeal position relative to the midline of the cervical vertebra. The CT slice of each subject within 5 mm cephalad of the cricoarytenoid joint was traced. Then, the deviation and rotation angles were measured using our method. Seventy one percent of the subjects' larynges deviated and/or rotated to the right side, while 17% to the left side. Six percent showed neither deviation nor rotation. As to the rest of 6%, deviation and rotation were in opposite directions. Besides, the length of the thyroid alae were measured in 282 subjects. Left ala was longer in 55%, and right was in 23%, and almost equal in 22%. The conclusions are as follows, 1. The majority of the subjects' CT images showed deviation and/or rotation of the laryngeal framework to the right side. 2. So called idiopathic laryngeal deviation is a case which observed in those cases with remarkable deviation and/or rotation of the laryngeal framework. 3. Aging seemed to be an important factor in acceleration of the laryngeal deviation and rotation. 4. The type of diseases and the side of mass lesions had no statistical significance in deviation and rotation of the larynx. PMID- 2319384 TI - [Surgical anatomy of the so-called dangerous frontal sinus (Boenninghaus)]. AB - Surgically dangerous type of frontal sinus was first reported by Boenninghaus in 1923. The present study concerns with the types and incidence of the dangerous frontal sinus as investigated by axial scans of HRCT. A total of 286 adult and 33 infant cases was included. The anterior end of the olfactory groove was first classified into three types, i.e., normal type, obliterated type (obliterated by cancellous bone) and dangerous type (with Recessus cristae galli and Torus olfactorius). In the adult, the incidences of these types are, 67.2, 18.5 and 14.3%. In the infant, incidences are 42.4, 51.5 and 6.1%. In the adult, the incidences do not differ in sex and sides. The dangerous type was classified into moderate and severe according to the depth of Recessus cristae galli, those with 1.5-2.9 mm depth are moderate and those over 3.0 mm are severe. The moderate dangerous type was seen in 30 sides and severe in 46 sides. In addition to the depth of Recessus cristae galli, distances from Torus olfactorius to the anterior sinus wall and the frontal skin surface were also included. These distances tend to be larger in male. PMID- 2319385 TI - [Inhibitory effect of nasal mucus on the absorption of drugs through respiratory epithelium]. AB - The absorption of Dibekacin (DKB) through rabbit's tracheal mucosa with and without nasal mucus were examined in vitro. The modified double chamber method was used for the purpose of this study. DKB solution (20 mg/ml) and Hanks' balanced salt solution were put into the donor compartment (DC) and the receiver compartment (RC), respectively. A plate with a hole and the tracheal mucosa were inserted between the compartments in the order of DC, dialytic membrane, the plate, the rabbit tracheal mucosa and RC. The hole of the plate was filled with nasal mucus or Hanks' solution. The latter was used as the control. The chamber was incubated in a humidified atmosphere of 5% CO2 in air for 3 hours at 37 degrees C. The absorption rate (AR) was obtained by dividing the concentration of DKB in RC by that in DC. The nasal mucus from patients with chronic sinusitis significantly decreased the AR of DKB compared with that in the control (P less than 0.05). The AR significantly decreased with increments in the thickness of nasal mucus by chronic sinusitis. This decreased AR was improved by the addition of N-Acetyl-L-cysteine (NAC) to DKB solution in DC. NAC can cleave disulfied bonds of mucus glycoprotein and this results in the decrease of viscoelasticity of nasal mucus. The results indicate that nasal mucus by chronic sinusitis intercept the absorption of drugs through respiratory epithelium in vitro. One of the mechanisms of the intercepter may be due to the high molecular-reticular structure of nasal mucus. PMID- 2319386 TI - [Visual scoring in the auditory brainstem response first report: judging the presence or absence of a response]. AB - The evaluation of visual scoring in the ABR audiometry was performed by the two groups of scorers 3 experienced and 3 inexperienced. The sample traces of responses for visual scoring were obtained from 3 normal adults, and consisted of 300 which were derived from 100 each on with clicks of 0, 5, 10, 15, 20, 30 dBSL and without stimulation. The forced choice method and the five confidence level method were applied from estimation when the traces were presented to the scorers separately on duplicatively. Judgment was given twice with a 2 months intervals. Results obtained were as follows: 1. The rate of positive responses in the forced choice method was 15% at 0dB and 96% at 15dB in the experienced group. 2. In the forced choice method the lowest rate that all scorers of a group had the same judgment, was 78% at 10dB in the experienced and 55% at 5dB in the inexperienced. 3. The lowest rate of the repeated judgments were same, was 90% at 10dB in the experienced and 79% at 0dB in the inexperienced. 4. The rate of the false positive response was significantly smaller in the duplicate presentation than in the separate one. 5. A tendency of great subjectivity was observed more often in the confidence level method than in the forced choice method, especially in the inexperienced group. PMID- 2319387 TI - [Correlation of proliferation index with submucosal invasion of hypopharyngeal cancer]. AB - Proliferation index of biopsied specimens from 11 cases of hypopharyngeal carcinoma was studied immunohistochemically using anti-BrDU monoclonal antibody. S-phase cell labelling index (SLI) was measured and compared with the extent of submucosal invasion that was evaluated histologically in each extirpated specimen by means of continuous large section technique. Conclusions were as follows: 1. The largest SLI was obtained in a moderately differentiated carcinoma, and calculated up to 56, while the smallest was encountered in a well differentiated carcinoma as 18. Mean value in these 11 cases was 35. 2. It seemed likely that moderately or poorly differentiated carcinomas show larger SLI, but its statistical significance could not be delineated in these materials. 3. Submucosal invasion was much longer in the oral direction than in the anal. The longest invasion was observed in a case that showed the largest SLI, and measured up to 22 mm. The shortest invasion, on the contrary, was seen in a case with the smallest SLI, and was only 9 mm. Mean value in these 11 cases was 14.4 mm. 4. SLI correlates well in every case to the extent of submucosal invasion toward the oropharynx. 5. SLI evaluated preoperatively in biopsied specimen may help to indicate an ample safety margin at the surgery. PMID- 2319388 TI - [Localization of inflammation of tympanic cavity in human temporal bone pathology]. AB - When we treat patients of otitis media, it is important to know the pathogenesis of otitis media. Therefore histopathological change of epithelium and bone in each site of tympanic cavity was observed using human temporal bones. Histopathological change of epithelium was classified as: acute, subacute and chronic in eighteen sites of tympanic cavity. Histopathological change of bone was observed in thirteen sites of tympanic cavity. And the frequency of histopathological change of epithelium and bone in each site was compared. A review of 350 temporal bones collected from autopsy cases revealed 171 (49.1%) to have otitis media, and a review of 170 temporal bones of otitis media cases revealed 165 (97.1%) to have bone changes. Differences in frequency of histopathological change of epithelium and bone existed in each site. Histopathological change in inferior portion of mastoid cells, round window niche and tympanic sinus was more frequent than in the other sites. Change of epithelium: in acute inflammation, no differences in frequency of histopathological change existed; in subacute inflammation and chronic inflammation, differences in frequency of histopathological change existed in each site. Change of bone: most changes were bone formation and bone reconstruction, but there was no clear finding that bone formation narrowed tympanic cavity without mastoid cells. Osseous destruction was found in mastoidectomy cases and cholesteatoma cases. It is thought that the frequency of inflammation is related to structure of cavity, aeration, immunologic activity or structure of the epithelium, and that the pathogenesis of otitis media, especially in chronic otitis media, is different in each site of tympanic cavity. It is thought that because the subjects of this study were not operated cases but autopsy cases, slight bone change was very frequent, but severe bone change, was rare. And we examined the pathogenesis of tympanic cavity of each case of acute inflammation and chronic inflammation of pars tensa and cases where there were no findings of inflammation in the pars tensa. In most cases of acute inflammation of pars tensa, inflammation of tympanic cavity was acute; in chronic inflammation of pars tensa, chronic. It was interesting that, in cases of normal pars tensa, inflammation was frequently found in tympanic cavity. Therefore, it is important to pay attention to the possibility of inflammation in tympanic cavity, even if the tympanic membrane appears normal. PMID- 2319389 TI - [An experimental study on the auditory brainstem response to electrical stimulation of the cochlea]. AB - This animal research was undertaken to study some important issues for cochlear implantation. This included investigations of 1) the difference in the auditory brainstem responses (ABRs) to extra- and intracochlear electrical stimulations. 2) stimulus parameters and ABRs to a bipolar intracochlear stimulation, and 3) electrode placements and ABRs. There were no distinct differences in waveforms and input-output curves of ABRs between extracochlear electrical stimulation and intracochlear bipolar stimulation of the cochlea. Changes in amplitude and latency of ABRs were investigated at changes of the pulse amplitude or the pulse width of stimulating electric rectangular waves. Increase in the pulse amplitude or the pulse width resulted in increase of the amplitude of ABRs and no increase in the ABR latency. This results showed the amplitude of ABR was dependent on the amount of electricity; coulomb. Electrically evoked ABRs were studied for stimulations at different sites of the cochlea. The ABR elicited with a bipolar electrode placed at the third turn of the cochlea had a longer latency of each peak of ABR waves than the one at the basal turn. This indicates that electrical stimulation with a bipolar electrode can give rise to a localized excitation in the cochlea and a latency change along the longitudinal axis of the cochlea, so that it suggests a multichannel cochlea implant system can transmit more information as a spacious pattern than a single channel system. PMID- 2319391 TI - The ultrastructure of plexogenic pulmonary arteriopathy. AB - The lungs from 16 cases of plexogenic pulmonary arteriopathy obtained at heart lung transplantation, half of which had primary pulmonary hypertension, were examined by electron microscopy. From these the probable pathogenesis of pulmonary arterial intimal fibrosis in plexogenic pulmonary arteriopathy was deduced. The earliest detectable change was migration of smooth muscle cells from the media, through the internal elastic lamina into the intima. These cells collected beneath the endothelium and lost many of their myofilaments to become myofibroblasts. They were associated with ground substance but scanty collagen fibrils. As the quantity of interstitial collagen increased, the myofibroblasts reverted to a muscular structure, became elongated, and assumed a regular, circumferential orientation. This later stage coincided with the development of plexiform lesions. At both early and later stages, the muscular pulmonary arteries were contracted but not markedly so, and muscular evaginations were not seen. On the other hand, the cellular intimal proliferations developed early and were occlusive. This suggests that occlusion of small pulmonary arterial vessels by myofibroblasts may be at least as important as vasoconstriction in the early elevation of the pulmonary vascular resistance in primary pulmonary hypertension. PMID- 2319390 TI - Epithelial-mesenchymal interactions can influence the phenotype of carcinoma metastases in the mucosa of the intestine. AB - In this paper we report two cases in which morphological differentiation of gastric adenocarcinoma has occurred when metastatic tumour was present within the lamina propria of the intestinal mucosa. In one case, there were metastases in the small intestinal mucosa and in the second case, in the mucosa of the appendix. The morphology of the intramucosal tumour simulated that of an adenomatous neoplasm. The recognition of this occurrence may be important in the differential diagnosis of primary and secondary adenocarcinomas of the gastrointestinal tract. The phenomenon is not only of diagnostic interest: the data presented here provide in vivo evidence that gastrointestinal carcinomas may differentiate in response to epithelial-mesenchymal interactions in a similar way to that seen in experimental models. PMID- 2319392 TI - Congenital echo virus infection--morphological and virological study of fetal and placental tissue. AB - A prospective study of 78 pregnant women was undertaken to detect maternal enterovirus infection. Maternal faecal specimens and blood samples, placental and fetal tissue were taken for viral study, electron microscopy, histochemistry, and morphological examination. We present the post-mortem findings in three fetuses whose maternal infection was detected before delivery by isolation of ECHO virus type 33 and type 27 from faecal specimens and/or placental and fetal tissues. The morphological aspects were similar in all cases and included an acute infection of the placenta and hypoxic/hypotensive injury to fetal organs. In one case, viral particles were detected by electron microscopy of the fetal liver. This series of cases of intrauterine ECHO virus infection confirms the potential gravity of such infection during pregnancy and the need to prevent enteroviral disease. PMID- 2319394 TI - Pathological Society of Great Britain and Ireland. 160th meeting. 3-5 January 1990, London. Synopses of papers. PMID- 2319393 TI - Immunohistochemical detection of proliferating lipocytes in regenerating rat liver. AB - For the detection of proliferating lipocytes in regenerating liver, partially hepatectomized rats were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdUrd, 50 mg/kg body weight) and killed 1 h later. Acetone-fixed frozen liver sections were used for the simultaneous detection of cytoplasmic desmin and BrdUrd-labelled nuclei of lipocytes using double immunohistochemical procedures. The best results were obtained with the sequences: rabbit anti-desmin--- biotinylated anti-rabbit IgG----avidin-biotin-peroxidase complex----3,3' diaminobenzidine tetrahydrochloride, followed by DNA denaturation----mouse anti BrdUrd----anti-mouse IgG----peroxidase-anti-peroxidase complex----4-chloro-1 naphthol. With this method, cytoplasmic desmin was stained a brown colour, which sharply contrasted with the blue-stained BrdUrd-labelled nuclei. Unlabelled nuclei appeared green after counterstaining with methyl green. No cross-reaction between immunoreagents of desmin and BrdUrd stainings was observed. The labelling index of lipocytes peaked (25.7 per cent) 48 h after partial hepatectomy, whereas it was 3.7 per cent in normal rat liver. PMID- 2319395 TI - Compensation under the National Childhood Vaccine Injury Act. AB - The purpose of this article is to look at the effect of the federal compensation scheme under the National Childhood Vaccine Injury Act on the people and institutions involved in the administration of vaccinations. More vaccine-injured children will probably receive compensation than would have been true under state law, but each child will probably receive less money for damages. Manufacturers will pay excise taxes to fund the compensation scheme and receive, in return, substantial immunity from liability under state law. Although these provisions create incentives that work in opposite directions, producers likely will still have reason to improve the safety and efficacy of vaccines. The situation for those who administer vaccinations is less clear. Freeing them from the threat of litigation would leave them with little incentive to use immunizations appropriately because they do not contribute to the compensation scheme. Although Congress intended to make those who give vaccines immune from state claims, it may have failed to do so, leaving providers with their liability largely unchanged. The most pervasive uncertainty is that the Act is designed to self destruct and may soon return vaccine-injured children, manufacturers, and providers to the state of the law before Congress acted. PMID- 2319396 TI - Prevalence and expression of familial combined hyperlipidemia in childhood. AB - The objectives of this study were (1) to determine the incidence of dominantly inherited hyperlipoproteinemia in children referred to our medical center because of hyperlipidemia associated with a family history of premature coronary artery disease and (2) to assess the degree of expression in childhood of the most common inherited hyperlipoproteinemia, familial combined hyperlipidemia. Among 129 families referred to us by area pediatricians, we identified a dominantly inherited hyperlipoproteinemia in 97 of them. Twenty had familial hypercholesterolemia, 65 familial combined hyperlipidemia, 11 hyperapobetalipoproteinemia, and one familial hypertriglyceridemia. As expected, almost half (9/20) of the siblings of probands with familial hypercholesterolemia were affected. Although we expected incomplete gene penetrance in the siblings of the probands with familial combined hyperlipidemia, we found 43 affected and 40 unaffected among the 83 siblings of the 65 probands. Our findings suggest that hyperlipidemia in children, caused by familial combined hyperlipidemia, occurs more than three times as frequently as familial hypercholesterolemia and that in families identified by a child proband, the penetrance is complete. Pediatricians should identify this primary hyperlipidemia in childhood and attempt to prevent the associated risk of premature coronary artery disease by prescribing appropriate diet and life-style modifications. PMID- 2319397 TI - Risk of sudden infant death syndrome in subsequent siblings. AB - To determine the risk of recurrence of sudden infant death syndrome in families, we studied 251,124 live births by linked birth and death certificates from Oregon for a 10-year period. We found five recurrences among 385 subsequent siblings, for a rate of 13/1000 live births and a relative risk of 6. When the recurrences were adjusted separately for birth order and maternal age, the risk was still five times that expected (p less than 0.001). Families with infant deaths from causes other than sudden infant death syndrome had similar recurrence rates, suggesting that the phenomenon was not specific to sudden infant death syndrome. The overall mortality rate for subsequent siblings after a sudden death event totaled 20.8/1000. We believe that a risk of 2%, although small in the design of studies of infants at risk for sudden infant death syndrome, is not trivial in the counseling of parents. PMID- 2319398 TI - Sudden infant death syndrome among Asians in California. AB - We analyzed California linked birth and infant death records for 1978 to 1985 to determine the ethnic-specific incidence of sudden infant death syndrome in five Asian-American subgroups, and to assess the association of sudden infant death syndrome with cultural assimilation. The overall incidence of sudden infant death syndrome for these groups was 1.1/1000 live births (194 cases). The ethnic specific incidence was statistically associated with the immigration status of each ethnic group, as measured by the proportion of all live births for which the mother was born in the United States, with a higher incidence for groups that have been in the United States for the longest period. A logistic model was used to examine simultaneously the association of sudden infant death syndrome with maternal ethnicity, ethnic homogeneity or heterogeneity of the parents, and maternal birthplace (United States, or elsewhere). The logistic analysis did not yield statistically significant evidence to support cultural assimilation as a factor in the incidence of sudden infant death syndrome for these groups. This finding may be due to small sample size and inadequate indicators of assimilation. It may also be that other factors relating to immigration and selective migration affect the incidence of sudden infant death syndrome among Asian-Americans. PMID- 2319399 TI - Subnormal serum concentrations of IgG2 in children with frequent infections associated with varied patterns of immunologic dysfunction. AB - To characterize more fully the immunologic basis for increased susceptibility to infection in patients with low serum concentrations of IgG2, we identified eight infection-prone children, 1 to 2 years of age, with serum IgG2 concentrations greater than 2 SD below the mean for age and followed their serologic and clinical courses for 1 to 3 years. Two of the eight children became clinically and immunologically normal and may have had transient IgG2 deficiency with an exaggerated developmental delay of this late-maturing subclass. The remaining six subjects had persistently subnormal or low-normal serum IgG2 levels and continued to experience frequent infections. All six of these children responded poorly to Haemophilus influenzae type b (Hib) polysaccharide, and four of six responded poorly to Streptococcus pneumoniae type 3 polysaccharide. Both IgG1 and IgG2 specific antibody responses to these vaccines were abnormal. Three of these six children also responded poorly to tetanus toxoid, an antigen that normally induces a predominant IgG1 response. Although five of these six children produced antibodies in response to Hib polysaccharide protein conjugate vaccine, three of four given Hib oligosaccharide CRM conjugate vaccine required booster doses to respond, a pattern of response characteristic of infants less than 6 months of age. Further, although serum concentrations of IgG1 were normal, peripheral blood mononuclear cells from four of six children tested produced extremely small amounts of IgG1 and IgG3 as well as IgG2. Finally, varied patterns of abnormalities of IgG, IgA, IgM, and IgG4 became apparent in five of the six children with persistently low serum IgG2 values. This study demonstrates that subnormal serum concentrations of IgG2 may be associated with varied patterns of immunologic dysfunction, some of which are evolving and may be responsible for increased susceptibility of these children to infection. PMID- 2319400 TI - Immunogenicity and safety of a pertussis vaccine composed of pertussis toxin inactivated by hydrogen peroxide, in 18- to 23-month-old children. AB - A new pertussis vaccine, composed of purified pertussis toxin inactivated by hydrogen peroxide and adsorbed onto aluminum hydroxide (NICHD-Ptxd), was injected into 60 children aged 18 to 23 months without a history of pertussis or pertussis vaccination. Two doses of toxoid, 10 and 50 micrograms, were used. Two injections, given 8 to 12 weeks apart, elicited increases in serum levels of antitoxin and IgG antibodies in 56 children who had no detectable antitoxin (less than 5 units) before vaccination. Four children with detectable antitoxin (greater than or equal to 5 units) before the first vaccination had pronounced antibody increases after the first dose. After the second dose, the geometric mean antitoxin concentration was 29 units with the 50 micrograms dosage and 10 units with the 10 micrograms dosage (p less than 0.001). Serum antibody levels elicited by two injections of 50 micrograms were similar to those in patients convalescing from pertussis. A third injection given to seven children 9 to 10 months after the second injection gave a booster response, with high levels of antitoxin (160 to 1280 units) and of IgG antibodies. With few exceptions the antibody response was restricted to the IgG class. Transient local reactions greater than or equal to 2 cm in diameter occurred in 14% of the children after the first dose and in 44% after the second and third doses. Moderate fever was recorded after 6% of all injections. There were no changes in peripheral blood leukocyte counts or fasting blood glucose levels measured before and 24 hours after the first injection. We conclude that NICHD-Ptxd is immunogenic in children. No serious adverse effects were noted. PMID- 2319401 TI - Long-term evolution of chronic hepatitis B in children with antibody to hepatitis B e antigen. AB - The aim of this study was to evaluate the long-term outcome of chronic hepatitis B in 27 children who had increased alanine aminotransferase activity and antibody to hepatitis B e antigen in serum from the time of their first clinical observation. Initial histologic changes were consistent with chronic active hepatitis in 13 cases (three with associated cirrhosis) and with persistent or lobular hepatitis in the remaining cases. On the basis of virologic testing, three groups of patients were identified: (1) two children had hepatitis delta antigen in the liver and anti-delta antibody in serum, and both had severe hepatitis; (2) 10 children had hepatitis B virus DNA in serum, and 60% of them had active hepatitis; (3) 15 patients had no hepatitis B virus DNA, and 33% of them had active hepatitis. During a follow-up period of 12 months to 12 years (mean +/- SD: 6.1 +/- 2.4 years), the disease remained active in both children with anti-delta antibody, but they had no major complaints. In all eight patients who could be followed in group 2, test results became negative for hepatitis B virus DNA and alanine aminotransferase activity normalized within 4 years; biochemical remission was delayed in three patients with higher hepatitis B virus DNA levels on entry, and one of these patients had a severe exacerbation of disease activity before remission. In group 3, a total of 10 patients (71%) achieved biochemical remission within 1 year, and two within 26 months; only two patients, who were transfused at birth, had long-lasting liver damage. These results indicate a trend to early remission of liver disease in children with chronic hepatitis B with antibody to hepatitis B e antigen without delta virus infection. Antiviral therapy aimed at accelerating the termination of hepatitis B virus replication may be indicated only in those with higher levels of hepatitis B virus DNA. PMID- 2319402 TI - Growth-stimulating effects of recombinant human growth hormone in children with end-stage renal disease. AB - Because patients with uremia have evidence for growth hormone resistance, we investigated whether this resistance can be overcome by administration of recombinant human growth hormone in supraphysiologic doses in children with severe uremia. Nine stunted children with end-stage renal disease (median age 5.8 years, median bone age 2.7 years) were treated with recombinant human growth hormone, 4 IU/m2/day subcutaneously, for a period of 1 year. Median height velocity was increased from 4.4 cm/yr before therapy to 8.0 cm/yr during treatment. Negative values for height velocity standard deviation scores for chronologic age were improved from a median of -2.6 to +1.5 without advancing bone age more than chronologic age. The growth hormone-insulin-like growth factor I resistance may be explained in part by the increased serum concentration of the high molecular weight insulin-like growth factor binding protein despite normal insulin-like growth factor I serum concentration. Treatment with recombinant human growth hormone improved the ratio between the serum concentrations of insulin-like growth factor I and its binding protein, and normalized the somatomedin bioactivity in the growth cartilage bioassay. PMID- 2319403 TI - Aortocoronary bypass surgery for coronary arterial lesions resulting from Kawasaki disease. AB - To establish the indications for aortocoronary bypass surgery on coronary artery lesions caused by Kawasaki disease, we analyzed surgical outcome in 26 patients. Ages at operation ranged from 1 to 17 years. All patients were followed up with selective coronary arteriography, thallium myocardial imaging, electrocardiography at rest, and the Master "two-step" and treadmill exercise tests for coronary insufficiency. Surgical outcome was analyzed by comparing results of patient examinations made preoperatively with those both at 1 month and 1 year postoperatively. One month after the operation, 25 (93%) of 27 internal mammary artery grafts and 6 (86%) of 7 saphenous vein grafts were patent; 1 year after the operation, 19 (86%) of 22 internal mammary artery grafts and 6 (67%) of 9 saphenous vein grafts were patent. By comparing the preoperative findings of myocardial imaging with those obtained 1 month after surgery, we found that 17 (68%) of 25 showed improvement and 3 (12%) of 25 were worse. At 1 year, 6 (29%) of 21 showed further improvement than at 1 month, suggesting increased development of the coronary bed after internal mammary artery graft anastomosis. Thus an internal mammary artery graft has proved to be satisfactory in the management of children with coronary artery obstruction caused by Kawasaki disease; it appears that both the quality of life and the life expectancy of those patients can be improved by the surgery. PMID- 2319404 TI - Abnormalities in serum osteocalcin values in children with chronic rheumatic diseases. AB - We studied bone mineral metabolism prospectively in 113 children with chronic rheumatic diseases (juvenile arthritis, systemic lupus erythematosus, and juvenile dermatomyositis) to determine the relationship of serum levels of osteocalcin to rheumatic disease activity and corticosteroid usage, and to determine, in part, the cause of osteopenia in this population. Disease activity was quantitated by historical, clinical, and serologic means and an activity score derived. The 113 children were divided according to the expression of their disease, which was active (group 1: mean score 3.42, mean erythrocyte sedimentation rate 28 mm/hr) or inactive (group 2: score 1.7, erythrocyte sedimentation rate 15 mm/hr) (p less than 0.02 group 1 vs group 2 for each value), or which remitted during the study (group 3). We found that serum levels of osteocalcin, but not those of ionized calcium, 25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, and parathyroid hormone, were reduced in group 1 children even before corticosteroid therapy was employed. Children in both group 2 and group 3 had normal osteocalcin levels despite the use of corticosteroids. The reduced levels of osteocalcin were predictive of a reduction in bone mass measured by photon absorptiometry in 16 of 19 children so studied. We conclude that skeletal abnormalities that result in a reduced bone mass occur in the clinical course of the majority of children with active chronic rheumatic diseases, are associated with reduced osteocalcin levels, and are not related to the use of corticosteroids. Serum osteocalcin levels may be a sensitive marker for reduced osteoblast activity and bone formation in children with chronic rheumatic diseases. PMID- 2319405 TI - Pigmentary abnormalities and mosaicism for chromosomal aberration: association with clinical features similar to hypomelanosis of Ito. AB - Thirteen patients with hypopigmentation of the skin characteristic of hypomelanosis of Ito, and with developmental disabilities or structural malformations, or both, were examined at our center. Eight were found to have abnormal karyotypes in lymphocytes, fibroblasts, or both. No single clinical feature was predictive of chromosome imbalance in this group of patients. Cytogenetic findings included a balanced de novo X-autosome translocation; ring 10; 45,X/46,X,+ring; mosaic del 13q11 (fibroblasts); mosaic triploidy (fibroblasts); mosaic tetrasomy 12p (fibroblasts); mosaic apparently balanced 15;22 translocation (peripheral blood); and mosaic trisomy 18 (peripheral blood). Hypomelanosis of Ito is characterized by swirly hypopigmentation or depigmentation of the skin with or without other malformations. Autosomal dominant, autosomal recessive, and X-linked dominant inheritance have been suggested but not confirmed. Chromosomal aneuploidy has also been reported. We believe that hypomelanosis of Ito is an etiologically heterogeneous physical finding, and recommend karyotyping of multiple tissues of all patients with abnormal cutaneous pigmentation associated with developmental delay or structural malformations. PMID- 2319406 TI - Chickenpox: where do we stand with treatment? PMID- 2319407 TI - Serum-soluble interleukin-2 receptor levels in Kawasaki disease. PMID- 2319408 TI - Weaver syndrome and instability of the upper cervical spine. PMID- 2319409 TI - Effect of medical and social risk factors on outcome of prematurity and very low birth weight. AB - A cohort of 129 infants with birth weights less than or equal to 1250 gm was followed for more than 4 1/2 years (mean +/- SD: 60 +/- 10 months) to determine the independent effects of two medical risk factors--intracranial hemorrhage and severe chronic lung disease--and a parenting risk factor (abuse or neglect) on neurodevelopmental outcome. In infants without any intracranial hemorrhage or parenting risk factors, severe chronic lung disease was not related to neurologic or cognitive outcome. Infants with increasing grades of intracranial hemorrhage had increasing rates of neurologic and cognitive abnormalities. However, the factor associated with the highest incidence of later abnormality was the parenting risk factor. We conclude that infants with medical risk factors may have additional social risk factors, and that both of these influences must be considered in an examination of the long-term sequelae of neonatal complications. PMID- 2319410 TI - Use of continuous infusion of pralidoxime for treatment of organophosphate poisoning in children. PMID- 2319411 TI - Phenylalanine metabolites in phenylketonuria. PMID- 2319412 TI - Effectiveness of clonidine in congenital orthostatic hypotension. PMID- 2319413 TI - Immune function during growth hormone therapy. PMID- 2319414 TI - Immunohistochemical demonstration of Trypanosoma evansi in tissues of experimentally infected rats and a naturally infected water buffalo (Bubalus bubalis). AB - Trypanosoma evansi was demonstrated by an immunohistochemical technique in formalin-fixed paraffin-embedded tissues of experimentally infected rats. Trypanosoma evansi was visible readily, nuclei were stained darkly, the cytoplasm was stained moderately, and the cell membranes were delineated clearly. The parasites were present in small- to large-sized blood vessels of all organs, in extravascular spaces of ventricles and neuropil of the brain, and in interstitial tissues of the lung and testes. This method also stained nuclei but not cytoplasm or cell membranes of Trypanosoma congolense, and did not stain Trypanosoma theileri. In a water buffalo (Bubalus bubalis) with nonsuppurative meningoencephalitis, the presence of T. evansi could not be demonstrated by conventional histological stains. However, the trypanosomes were recognized readily in the Virchow-Robin spaces and neuropil of the brain by the immunohistochemical method. PMID- 2319415 TI - A novel anthelmintic model utilizing jirds, Meriones unguiculatus, infected with Haemonchus contortus. AB - Currently, no in vivo laboratory model is available for evaluating anthelmintics against the important ruminant helminth Haemonchus contortus. This report outlines a novel anthelmintic assay utilizing immunosuppressed (0.02% hydrocortisone in feed) jirds, Meriones unguiculatus, infected with H. contortus. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of H. contortus, treated per os on day 10 postinoculation (PI), and necropsied on day 13 PI. Each stomach was removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Stomach contents were examined using a stereomicroscope (15-45x). A variety of standard anthelmintics has been evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses (mg/kg) comparable to those required for efficacy against H. contortus in ruminants. This model provides an important new tool to assess preliminarily the activity of experimental drugs against H. contortus in vivo prior to studies in ruminants and also may provide a useful tool for studying host-parasite interactions for H. contortus. PMID- 2319416 TI - Effects of sulfadiazine and amprolium on Neospora caninum (Protozoa: Apicomplexa) infections in mice. AB - An immunosuppressed mouse model was used to determine the effects of amprolium and sulfadiazine on experimental Neospora caninum infections. Both drugs were given in the drinking water. Neither drug was effective in treating infections when given 7 days after inoculation of tachyzoites, when clinical signs of disease had developed. Amprolium did not prevent deaths or development of clinical signs when given in the drinking water at 1 mg/ml or 5 mg/ml 3 days after inoculation of tachyzoites. Sulfadiazine in drinking water was not effective when given at 0.5 mg/ml but was effective in preventing deaths and clinical disease when given at 1 mg/ml 3 days after inoculation with tachyzoites. Most mice (6 of 10) treated for 3 days with 1 mg/ml sulfadiazine in drinking water developed encephalitis after drug treatment was stopped. Treatment for 14 days with 1 mg/ml sulfadiazine in drinking water was needed to protect 90% of inoculated mice. PMID- 2319417 TI - Experimental and theoretical studies of albendazole, oxibendazole, and tioxidazole. AB - An investigation of the therapeutic effectiveness of albendazole (ABZ, methyl 5 [propylthio]benzimidazole-2-carbamate), oxibendazole (OBZ, methyl 5-[n propoxy]benzimidazole-2-carbamate), and tioxidazole (TIOX, methyl 6-[n propoxy]benzothiazole-2-carbamate) against Hymenolepis diminuta in experimentally infected rats is reported. All of the anthelmintics tested were effective therapeutically as a single oral dose against adult tapeworms, however, at different dose levels. The rank order of in vivo anthelmintic potency was ABZ greater than OBZ greater than TIOX. Molecular modeling revealed that drug efficacy depends on the orientation of the propyl group at position 5 on the heterocyclic ring system and on the magnitude of the molecular dipole moment. PMID- 2319418 TI - Laboratory selection of a benzimidazole-resistant isolate of Trichostrongylus colubriformis for ivermectin resistance. AB - In vivo ivermectin resistance was selected in an isolate of Trichostrongylus colubriformis (TcR) already known to be benzimidazole resistant. This was accomplished in sheep by using levels of ivermectin calculated to reduce the fecal egg output from each generation of T. colubriformis by congruent to 95%. The first indication of ivermectin resistance was observed with the F10. A dosage titration trial comparing the parent TcR with the ivermectin-selected F21 demonstrated that the latter was congruent to 20 times more resistant to oral ivermectin therapy in experimentally infected sheep than was the parent isolate. Treatment of the F16 generation with 50 mg/kg of thiabendazole resulted in only 54% egg reduction and confirmed that benzimidazole resistance was stable. PMID- 2319419 TI - A study on the prevalence and intensity of occurrence of Thelazia skrjabini (Nematoda: Thelazioidea) in cattle in central Alberta, Canada. AB - The distribution of Thelazia skrjabini in the eyes of cattle was examined from necropsies on 297 animals. Although the overall prevalence in beef cattle (21.5%) was similar to that in dairy cattle (25.7%), in general worms were more abundant in beef than in dairy animals. The worm prevalence was lowest in the months from March to June and highest in September among beef and dairy animals. Thelazia skrjabini was found in 76 (16.8%) eyes from beef, and 23 (16.4%) eyes from dairy cattle. Infections were not randomly distributed among the eyes of cattle. Significantly more dairy and beef cattle contained T. skrjabini in both eyes than expected based on the observed prevalences. Based on chi-square probabilities, significantly more cattle more than 2 yr of age and less than 10 mo of age were infected with T. skrjabini. Although all age groups were infected, more worms were observed in cattle more than 2 yr of age. More female worms than males were collected from cattle. The male-to-female ratio of 1:2 was consistent regardless of cattle age, season, or type. PMID- 2319420 TI - Effect of high temperature on infectivity of Toxoplasma gondii tissue cysts in pork. AB - To study the effect of high temperature on infectivity of Toxoplasma gondii tissue cysts, pork from infected pigs was mixed with infected mouse brains and homogenized thoroughly. Twenty-gram samples of infected homogenized meat were sealed in plastic pouches, pressed to a uniform thickness of 2 mm, and subjected to water-bath temperatures of 49, 52, 55, 58, 61, 64, and 67 C for 0.01, 3, 6, 9, 12, 24, 48, and 96 min. Treated samples were digested in HCl-pepsin solution and bioassayed in mice. Toxoplasma gondii tissue cysts remained viable at 52 C for 9.5 min but not for 9.5 min at 58 C; tissue cysts were generally rendered nonviable by heating to 61 C or higher temperature for 3.6 min. Tissue cysts survived once at 64 C for 3 min. These data demonstrate that T. gondii tissue cysts are less heat resistant than encysted Trichinella spiralis larvae. PMID- 2319421 TI - Development of the excretory bladder of the lung fluke Paragonimus ohirai (Trematoda: Troglotrematidae). AB - The excretory bladder of Paragonimus ohirai was studied during development in rats. Parasites were obtained at each development stage, and single worms were prepared for both transmission and scanning electron microscopy (SEM). During early transformation (1, 2 days), excretory materials such as calcareous concretions and lipid droplets filled the bladder, and Golgi complexes and various types of cytoplasmic bodies were abundant. The bladder epithelia of late transformation (3, 5 days) were characterized by dense granules and glycogen concentration around lipid droplets. In differentiating bladders (7, 10 days), rough endoplasmic reticulum, ribosomes, and alpha-glycogen were extensive in the epithelia, whereas concretions had disappeared. The apical surfaces of the epithelia were highly folded and lamellated, and lamellae were seen associated with fingerlike cytoplasmic projections (10 days) and spherical cytoplasmic bulges (15, 20 days). During maturation, SEM revealed nuclear profiles (20 days) and a muscular framework (30 days) in relief. PMID- 2319422 TI - Humoral factors and nonspecific immune suppression in Syrian hamsters infected with Leishmania donovani. AB - Leishmania donovani produces progressive wasting and ultimately fatal visceral leishmaniasis in Syrian hamsters and provides an excellent model of progressive disease in humans. Experimentally infected hamsters were used to investigate the development of nonspecific immune suppression during visceral leishmaniasis and its association with humoral factors and wasting. At 2 wk all infected hamsters had developed antibody against a 59-kDa parasite antigen not recognized by sera of control hamsters. By 4 wk, strong antibody responses were noted against antigens of 26, 35, 46, 69, 107, and 120 kDa. No additional antigen was recognized at 6 or 8 wk or in hamsters treated with high doses of a pentavalent antimonial (stibogluconate sodium, 100 mg/kg/day for 5 days). Weight loss was first noted in infected hamsters at 8 wk. No difference in splenic lymphocyte proliferation in response to concanavalin A (Con A) was noted at 2 wk, but by 6 wk infected animals had only 20% of the Con A response of controls, and by 8 wk only 13%. Furthermore, incubation of splenic lymphocytes from uninfected control animals with 5% fetal calf serum and 5% serum from infected hamsters obtained at 4, 6, or 8 wk suppressed Con A responses by 50%, 99%, and 100%, respectively. Spleen cells from drug-treated animals exhibited no suppression of Con A responses when incubated with 5% autologous serum, but there was profound suppression when they were incubated with 5% autologous serum obtained during the acute phase of infection. Humoral factors, but not wasting, contributed to the suppression of lymphocyte responses. PMID- 2319423 TI - Differential binding of hemolymph proteins from schistosome-resistant and susceptible Biomphalaria glabrata to Schistosoma mansoni sporocysts. AB - Humoral factors have been associated with resistance of Biomphalaria glabrata to infection by Schistosoma mansoni. The goal of this study was to determine which serum (cell-free hemolymph) proteins bind to the surface of S. mansoni sporocysts. For this, 125I-labeled serum from schistosome-resistant (10-R2) and susceptible (M-line) B. glabrata was incubated with sporocysts, washed, and then subjected to SDS-PAGE and autoradiography. Other samples examined included radiolabeled 10-R2 and M-line serum, sporocysts incubated with unlabeled serum followed by incubation with radiolabeled serum, and radiolabeled sporocysts. Results indicated that many polypeptides in the serum from both strains of B. glabrata were radiolabeled. Dominating both profiles were bands in the 90-210-kDa range. However, some differences between the serum of the 2 snail strains were observed with M-line serum having several radiolabeled polypeptides in the 31-40- and 66-85-kDa range that were absent in serum from 10-R2 B. glabrata. When sporocysts were incubated with radiolabeled serum, 3 polypeptides (116, 180, 210 kDa) from both snail strains bound to the surface of the parasite. Further, a 55 kDa polypeptide bound to sporocysts incubated with 10-R2 serum but did not bind to those parasites incubated with M-line serum. Preincubation of sporocysts with unlabeled serum prior to incubation with radiolabeled serum significantly inhibited the uptake of radiolabeled proteins. This differential binding of serum polypeptides from different strains of B. glabrata may be important in determining resistance or susceptibility of the snail to larval schistosome infection. PMID- 2319424 TI - A spectrum of antibody response with time after Trichinella spiralis infection in rats. AB - A chronology of class-specific antibody response against the Trichinella spiralis infection in Fischer rats was investigated. G-class antibodies against the cuticle inner layer(s), hypodermis, hemolymph, glycogen aggregates, discrete areas in genital primordial cells, intestinal gland cell granules, and cytoplasmic granules in the cords were detectable 2 wk after infection (the rapid responding group), whereas G-class antibodies against the cuticle surface, stichocyte granules, and the esophagus-occupying substance were detected 6 wk after infection (the slow-responding group). M-class antibodies recognized a narrower spectrum of antigens than did G-class antibodies; M-class antibodies against hemolymph, cord granules, and intestinal gland cell granules were not detectable. M-class antibodies tended to decrease in titer with time after infection. This tendency was more striking with antibodies against the rapid responding group than with those against the slow-responding group. This information sheds light upon antibody response against many antigenic components of T. spiralis muscle larvae. PMID- 2319425 TI - Uniform strobilar development of Echinococcus multilocularis in vitro from protoscolex to immature stages. AB - The aim of this study was to obtain uniformity in strobilar development of Echinococcus multilocularis from protoscoleces in vitro. The isolate of E. multilocularis used was derived initially from a human case in France and subsequently maintained in the laboratory by intraperitoneal passage in Meriones unguiculatus. Protoscoleces used for culture were obtained using preparative procedures in which parasite tissue was disrupted gently with minimal exposure to pepsin and acidic conditions followed by immediate exposure to pancreatin in alkaline solution. Resultant cultures contained large numbers of evaginated, active, vermiform stages, which exhibited uniform strobilar development with formation of the first proglottid and segment and limited maturation of the first proglottid. All worms that exhibited proglottization subsequently segmented. Further proglottization did not occur and all worms degenerated within a few days following segmentation. The results are discussed in light of current knowledge of the relationships of somatic and germinal processes in Echinococcus. In view of these results, further studies should be encouraged to improve strobilar development of E. multilocularis in vitro. PMID- 2319426 TI - Scanning electron microscopy of the sheathed infective larva and parasitic third stage larva of Haemonchus contortus (Nematoda: Trichostrongyloidea). AB - Scanning electron microscopy was used to describe the infective and parasitic third-stage larvae of Haemonchus contortus, the large stomach worm of ruminants. Infective larvae are ensheathed in the cuticle of the second stage, so the descriptions are of the second- and third-stage cuticles. Both larval stages had an inner circle of 6 labial papillae, an outer circle of 6 labial papillae and 4 somatic papillae, and lateral amphidial pits. Infective larvae (cuticle of the second stage) had the 6 internal labial papillae on prominent bluntly rectangular lappets in a star-shaped arrangement around a large triradiate mouth, small triangular or round amphidial pits, flattened ribbonlike lateral alae, and phasmidial apertures opening on the ventral surface of the lateral alae. Parasitic third-stage larvae had the 6 internal labial papillae on small elevations without lappets around a small mouth; large, oval amphidial pits; ribbonlike lateral alae for most of their length, but with the anterior 30-40 microns of the alae cordlike; and phasmidial apertures on the body cuticle ventral to the lateral alae. PMID- 2319427 TI - A first case of myiasis in fish. AB - Maggots of an unidentified species of Caliphora were discovered in freshwater fish, Astyanax mexicanus fasciatus, shipped from Hong Kong to Norway. This represents the first reported case of myiasis in fish. PMID- 2319428 TI - Tissue "cysts" of Hepatozoon griseisciuri in the grey squirrel, Sciurus carolinensis: the significance of these cysts in species of Hepatozoon. AB - The lungs of a grey squirrel infected with Hepatozoon griseisciuri contained, in addition to typical haemogregarine schizonts, small cysts, each of which contained a single cystozoite. The presence of these cysts, which resemble those recorded in Hepatozoon species in reptiles, suggests that they may be a common feature in all Hepatozoon species and that these parasites may be transmitted by predation as well as by ingestion of infected arthropod vectors. PMID- 2319429 TI - Nutrient broth for the cultivation of Leishmania. AB - Nutrient broth containing fetal calf serum was used successfully in isolating Leishmania donovani from animals and cryopreserving Leishmania major, Leishmania donovani, and Leishmania adleri. It also supported heavy growth of promastigotes of laboratory strains of L. donovani, L. major, L. adleri, and uncharacterized reptilian Leishmania-like flagellates. PMID- 2319430 TI - Fatal toxoplasmosis in koalas (Phascolarctos cinereus). AB - Toxoplasma gondii-like organisms were seen in the heart, kidney, liver, lung, lymph node, spleen, small intestine, and stomach from 2 koalas that died suddenly in a fauna park in Sydney, Australia. Diagnosis was confirmed by immunohistochemical staining. This is the first confirmed report of toxoplasmosis in an arboreal marsupial. PMID- 2319431 TI - Purification of antigen B from Taenia solium cysticerci by affinity to mammalian collagen. AB - A 1-step procedure for the easy and rapid purification of milligram amounts of antigen B from a crude extract of Taenia solium cysticerci is described here. This procedure takes advantage of the property of the antigen B to bind to collagen and is based on antigen adsorption to polymeric collagen. PMID- 2319432 TI - Immune competence of Aedes trivittatus hemocytes as assessed by lectin binding. AB - Hemocytes were perfused from uninoculated, saline-inoculated, and Dirofilaria immitis microfilariae-inoculated Aedes trivittatus and assessed for their capacity to bind wheat germ agglutinin (WGA). Approximately one-fourth of perfused hemocytes were WGA positive in all groups of mosquitoes at all time periods tested. Results suggest A. trivittatus has a larger inherent population of immune-competent hemocytes as compared with Aedes aegypti and, therefore, is faster and more effective in killing microfilariae by melanotic encapsulation reactions. PMID- 2319434 TI - Age-related changes of the susceptibility to infection with Brugia pahangi in male and female BALB/c mice. AB - Effects of host age and sex on murine Brugia pahangi infection were examined. In female BALB/c mice, partial resistance to B. pahangi developed rapidly with age. In animals inoculated at 5-6 wk of age, resistance was about 2 times higher than in the youngest group (2-3 wk) and remained at a similar level through the study period (12 wk). Male BALB/c mice showed a similar tendency until 5-6 wk of age, but afterward their susceptibility increased with age. Significant difference in the susceptibility was detected between sexes after sexual maturation. After macrophage blockade by an injection of carbon particles into the mice, the age- and sex-related differences were completely abolished. This suggests that macrophages might have an important role(s) in the age- and sex-related changes of susceptibility to B. pahangi in BALB/c mice. PMID- 2319433 TI - New host and locality record for Trypanosoma peromysci. AB - Trypanosoma peromysci Watson, 1912 (Sarcomastigophora: Kinetoplastida), is described from a new host and locality. One of 20 (5.0%) Peromyscus leucopus collected from Pottawatomie and Riley counties in Kansas was found to harbor the parasite. Morphometric and statistical analysis confirmed the trypanosome to be indistinguishable from T. peromysci, the only difference being a greater mean flagellar length than reported previously. This is the first reported occurrence of T. peromysci in the white-footed mouse (Peromyscus leucopus noveboracensis Fischer, 1829) and also the first record of its occurrence in Kansas. PMID- 2319435 TI - Myxozoa of deep-sea fishes in the northwestern Atlantic. AB - The gall bladder of 5 species of deep-water fishes (Coryphaenoides armatus, Coryphaenoides rupestris, Macrourus berglax, Antimora rostrata, and Synaphobranchus kaupi) from the New York Bight and Carson Canyon areas in the northwest Atlantic were examined for myxozoan parasites. Myxidium coryphaenoidium was found in 4 fish species, whereas Auerbachia pulchra and Ceratomyxa sp. were each observed in 1 fish species. Prevalence of myxozoan infections was greater in fishes taken off the New York Bight than from the Carson Canyon. PMID- 2319436 TI - Experimental verification of the metacercarial stage of Rhipidocotyle lepisostei (Trematoda: Bucephalidae) with notes on the natural occurrence of its adult stage in gars in Texas and Virginia. AB - Bucephalid metacercariae found encysted in the caudal fin rays of striped mullet (Mugil cephalus) were fed to bucephalid-free spotted gars (Lepisosteus oculatus) in the laboratory. Gravid specimens of Rhipidocotyle lepisostei were recovered from the intestinal tracts of 2 of 3 gars from 7 to 28 days later. Further attempts to complete the entire life cycle were unsuccessful. Natural infections of adult R. lepisostei were found in the type host, the alligator gar Lepisosteus spatula, from Galveston Bay, Texas, and in the long-nose gar, Lepisosteus osseus, from the York River, Virginia. This report confirms the identity of the metacercarial stage in the mullet as R. lepisostei and extends the known range of this parasite from the Louisiana and Texas area to the U.S. Atlantic coast. PMID- 2319437 TI - Biphasic calcium phosphate ceramic combined with fibrillar collagen with and without citric acid conditioning in the treatment of periodontal osseous defects. AB - The purpose of this study is to determine whether the combination of biphasic calcium phosphate ceramic (BCP) and collagen and citric acid root conditioning would promote accelerated new attachment of periodontal tissue to the root surface in dogs. Intrabony defects were surgically produced for each animal and were made chronic for 16 weeks. These defects were assigned to two study treatment and one control group: ceramic-collagen without citric acid (CO-CE); ceramic-collagen with citric acid (CO-CE-CA); and control (surgical debridement and root planing only). Results showed that all groups gained new attachment level as demonstrated both clinically and histometrically. The treatment groups showed a significant mean gain greater than the control (P less than .005), but no significant difference was found between treatment groups. Small areas of ankylosis was also found in both treatments but there was no evidence of active root resorption. It is concluded that the use of combined BCP and fibrillar collagen is beneficial in promoting new attachment of periodontal tissues to the root surface in dogs. Although citric acid root conditioning did as well or better than ceramic and collagen alone, its benefits are still speculative and need further experimentation. PMID- 2319439 TI - Occurrence of periodontitis in an urban adolescent population. AB - The presence of periodontitis in 307 black, Hispanic, and Asian students age 12 to 15 years was evaluated by calibrated examiners in a Los Angeles inner city junior high school. The periodontal status of maxillary and mandibular incisors and permanent first molars was evaluated using the Plaque Index, probing depth, attachment loss, bleeding on probing, tooth mobility, presence of calculus, and caries. Thirty-nine (12.7%) of 307 students had 5 mm or deeper probing depths and associated attachment loss of at least 2 mm and were considered to have periodontitis (PD). The PD group had significantly more bleeding, calculus, and missing teeth than the non-PD group, but both groups had moderate to severe plaque accumulation. The distribution and severity of disease increased with age. Deeper probing depths were associated with the molar teeth and six (15.4%) of the 39 subjects in the PD group had furcation involvement. Clinical screening alone was not sufficient to determine if the periodontitis seen was localized juvenile periodontitis; however, the program detected a high occurrence of periodontitis in this population group. PMID- 2319438 TI - Neutrophil surface protein markers as indicators of defective chemotaxis in LJP. AB - Abnormalities of neutrophil function have been highly correlated with severe, early onset periodontal diseases. Nonetheless, the identification of these patients and diagnosis of specific disease states, such as LJP or prepubertal periodontitis, are difficult and costly. In this report, the identification and quantification of neutrophil cell surface markers specific to LJP patients with neutrophil chemotaxis defects are described. GP110 and FMLP receptors were quantified by flow cytometry on neutrophils from LJP patients with neutrophil chemotaxis defects, LJP patients without chemotaxis defects, other patients with primary neutrophil chemotaxis defects, and controls. Results suggest that reduction of GP110 and FMLP receptor on neutrophils is specific for LJP patients who exhibit neutrophil chemotaxis abnormalities. PMID- 2319440 TI - The association between palatal grooves in upper incisors and periodontal complications. AB - Palatal groove is a rare morphological defect of upper incisors, frequently associated with localized destruction of periodontal tissue with endodontic complications. In this study, a sample of 1,081 male, young adult subjects, aged 20 to 22, palatal grooving was recorded in 11 (1.01%) subjects, affecting 15 incisors. Among 634 adult subjects, aged 35 to 50, with periodontal disease, palatal groove was found in 5 (0.79%) incisors. Second incisors were more frequently (75%) associated with this anomaly. In the young adults, the mean probing pocket depth in the groove region and around other teeth of the intercanine area was 3.8 mm and 1.2 mm, respectively. In the group of periodontal patients, the mean probing pocket depth was significantly greater at the site of palatal groove (8.8 mm vs. 4.0 mm). PMID- 2319441 TI - Interaction between affect and cognition in word perception. AB - Investigated the hypothesis that the accuracy with which a briefly shown word is perceived depends on both the affective tone of the word and the activation of the corresponding memory code. To increase activation, expectation and word frequency were manipulated. Ss were exposed to a 25-ms flash of a target word. They then chose, from a word pair, the target word. In half the trials, this word pair was given before the flash to create an expectation. Consistent with the hypothesis, when the words were infrequent, accuracy in perception was lower for affective than for neutral words regardless of expectation. When the words were frequent, there was no effect of affective tone in the absence of expectation; in the presence of expectation, accuracy was higher for affective than for neutral words. The valence of the affective words had no effect. Results are interpreted in terms of attentional mechanisms implicated in conscious perception. PMID- 2319442 TI - Cognitive representation of conversations about persons. AB - Ss listened to a man and woman discuss the behaviors of a third, target person. First, however, they received handwritten sets of trait adjectives that each speaker had ostensibly used to describe the target before engaging in the conversation. Ss with the objective of forming an impression of the target person had better recall of behaviors if they were evaluatively inconsistent with the female speaker's trait description of the target. However, the behaviors' consistency with the male speaker's description of the target had little influence. When Ss listened to the conversation with instructions to infer each speaker's impression of the target, they typically had better recall of behaviors that were inconsistent with trait descriptions provided by the particular speaker who mentioned them. When they were told to form impressions of the speakers themselves, however, Ss had generally better recall of the behaviors mentioned by a given speaker when they were inconsistent with the trait description provided by the other speaker. Existing models of person memory and judgment could not account a priori for either these results or for judgments of the target and speakers. PMID- 2319443 TI - Continuity and change: assortative marriage and the consistency of personality in adulthood. AB - How is personality stability possible amid the myriad of social changes and transformations that characterize a human life? We argue that by choosing situations that are compatible with their dispositions and by affiliating with similar others, individuals may set in motion processes of social interchange that sustain their dispositions across time and circumstance. To test this proposition we examined mate selection, using data on married couples from two ongoing longitudinal studies at the Institute of Human Development, University of California, Berkeley. Consistent with other research, the results point to homogamy as a basic norm in marriage. More important, the results show that marriage to a similar other promotes consistency in the intraindividual organization of personality attributes across middle adulthood. We offer some speculations for a more relational approach to the problem of individual continuity and change. PMID- 2319444 TI - Reducing the dependence of clinical judgment on the immediate context: effects of number of categories and type of anchors. AB - Two experiments explored methods for standardizing ratings of the psychopathology of clinical case histories. In both experiments, the same case histories were rated as more pathological when mostly mild rather than severe cases were presented as the immediate context. Psychometric analyses demonstrated that this type of contextual effect is a potentially important source of unreliability in clinical judgment. In Experiment 1, increasing the number of points in the rating scale from 3 to either 7 or 100 significantly reduced the effects of the immediate context. Ratings were parsimoniously modeled by Parducci's (1983) range frequency theory. In Experiment 2, providing verbal anchors in the form of either detailed DSM descriptions for each rating category or sample case histories for the two end-categories increased the reliability of the ratings by reducing the effects of the immediate contexts; however, these reductions occurred only when the ranges of the immediate contexts had been severely restricted. According to the range-frequency analysis, verbal anchors served to equate the endpoints of the subjective range for the different contextual conditions. Comparison with previous research suggests that the anchors also reduced the effects of the sequential position in which clinical cases appear. We therefore recommend that studies of the reliability of behavioral assessment techniques take into account the effects of differences in context. PMID- 2319445 TI - Approach-withdrawal and cerebral asymmetry: emotional expression and brain physiology. I. AB - In this experiment, we combined the measurement of observable facial behavior with simultaneous measures of brain electrical activity to assess patterns of hemispheric activation in different regions during the experience of happiness and disgust. Disgust was found to be associated with right-sided activation in the frontal and anterior temporal regions compared with the happy condition. Happiness was accompanied by left-sided activation in the anterior temporal region compared with disgust. No differences in asymmetry were found between emotions in the central and parietal regions. When data aggregated across positive films were compared to aggregate negative film data, no reliable differences in brain activity were found. These findings illustrate the utility of using facial behavior to verify the presence of emotion, are consistent with the notion of emotion-specific physiological patterning, and underscore the importance of anterior cerebral asymmetries for emotions associated with approach and withdrawal. PMID- 2319446 TI - The Duchenne smile: emotional expression and brain physiology. II. AB - Facial expression, EEG, and self-report of subjective emotional experience were recorded while subjects individually watched both pleasant and unpleasant films. Smiling in which the muscle that orbits the eye is active in addition to the muscle that pulls the lip corners up (the Duchenne smile) was compared with other smiling in which the muscle orbiting the eye was not active. As predicted, the Duchenne smile was related to enjoyment in terms of occurring more often during the pleasant than the unpleasant films, in measures of cerebral asymmetry, and in relation to subjective reports of positive emotions, and other smiling was not. PMID- 2319447 TI - Imagery vividness, hypnotic susceptibility, and the perception of fragmented stimuli. AB - Two experiments were conducted to determine the role of hypnotic susceptibility level (high or low) and imaging ability (vivid or poor) in the performance of gestalt closure tasks. In Experiment 1, subjects were required to identify fragmented stimuli in the Closure Speed Test and in the Street Test. In Experiment 2, subjects reported on fragmented stimuli that were projected to the right eye and subsequently produced an afterimage. Individuals were asked to identify the composite if possible and to report on the duration of the afterimage. In both experiments, hypnotic susceptibility level and imaging ability affected reports of gestalt closure. The greatest number of correct closures was reported by those who were both high in hypnotic susceptibility and vivid in imaging ability. In addition, in the second experiment, this group also reported the longest enduring afterimage. These results are discussed in terms of the processes required to perform in a gestalt closure task. PMID- 2319448 TI - Conjunctive moderator variables in vulnerability and resiliency research: life stress, social support and coping skills, and adolescent sport injuries. AB - In life event research relating to vulnerability and resilience factors, single moderator variables have typically been the focus of study. Little is known about the ways in which moderator variables may interact with one another to increase vulnerability or resilience. We propose a distinction between conjunctive moderation, in which multiple moderators must co-occur in a specific combination or pattern to maximize a relation between a predictor and an outcome variable, and disjunctive moderation, in which any one of a number of moderators maximizes the predictor-criterion relation. Our results indicate that social support and psychological coping skills are statistically independent psychosocial resources and that they operate in a conjunctive manner to influence the relation between life stress and subsequent athletic injury in adolescents. Only athletes low in both coping skills and social support exhibited a significant stress-injury relation, and in that vulnerable subgroup, negative major life events accounted for up to 30% of the injury variance. Methodological considerations in the assessment of conjunctive moderator effects are discussed. PMID- 2319449 TI - Tragedy and ministry at midlife: Rena Bodie's incredible story. PMID- 2319450 TI - Adoption: a gift of life and love. PMID- 2319451 TI - Life's greatest gift. PMID- 2319452 TI - Facing fear in the burn center. PMID- 2319453 TI - After the abortion: watching an unwanted baby die. PMID- 2319454 TI - The moral defect in fetal tissue research. PMID- 2319455 TI - Can one nurse influence a nurses' convention? PMID- 2319456 TI - Ethanol inhibits zymosan-stimulated and enhances nonstimulated platelet activating factor production in a clonal macrophage cell line. AB - Ethanol was examined for its effects on zymosan phagocytosis and synthesis of platelet-activating factor (PAF) using a clonal macrophage cell line. PAF, identified as 1-O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine, is a biologically active ether phospholipid produced by various cells types. PAF also activates a variety of inflammatory cells including the cells which produce PAF. Ethanol at 20 to 100 mM inhibited phagocytosis of unopsonized zymosan and concomitantly decreased PAF concentration in the stimulated macrophages. In contrast, in cells not stimulated with zymosan, ethanol increased the recoverable PAF. Ethanol, at 100 mM, inhibited the uptake of exogenous PAF but did not alter the distribution of PAF metabolites in the clonal macrophage cell line. The effect ethanol has on PAF synthesis appears dependent on the activation state of the cell. Two situations were identified in this study: 1) one linked to phagocytosis or cell stimulation which is inhibited by ethanol, and 2) PAF synthesis which is not dependent on overt cell activation that is enhanced by ethanol. PMID- 2319457 TI - Effects of endothelium on basal tone and agonist and O2 sensitivity in porcine coronary artery. AB - Paired rings of porcine left anterior descending artery, with and without endothelium as determined by thrombin-induced relaxation, were suspended for isometric force measurement in Krebs solution (95% O2-5% CO2). The response to 50 mM KCl was similar in both preparations, averaging 59.3 +/- 2.5 mN/mm2 (n = 28). In the absence of any treatment, de-endothelialized rings (-E) spontaneously contracted; i.e., a basal tone of 21.8 +/- 2.0% of the control 50 mM KCl contraction was measured against the base line after an N2-induced relaxation. Intact rings (+E) developed a basal tone of only 1.8 +/- 0.7% (n = 14). Upon decreasing PO2 in the bath from 95 to 20%, (approximately 665-140 Torr) -E showed a 12.9 +/- 2.8% increase in force compared with only 1.5 +/- 0.6% for +E (n = 10). Norepinephrine also preferentially constricted the -E rings (1 x 10(-6) M: E = 13.6 +/- 2.0%, +E = 0.6 +/- 0.3%; 3 x -6 M: -E = 21.7 +/- 3.1%, +E = 3.3 +/- 1.1%, n = 8). A similar increase in sensitivity of the -E compared with the +E ring was observed for methoxamine, a nonmetabolized, alpha-1-selective agonist, KCl, Bay K 8644 and histamine, suggesting that the level of tone and not the endothelium per se underlies the changes in sensitivity. To test this hypothesis, the vasoconstrictive effects of decreasing PO2 and norepinephrine were also studied with tone altered by 10 mM KCl which increased the tone in both -E and +E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319458 TI - Nerve and drug-induced release of adenine nucleosides and nucleotides from rabbit aorta. AB - The purpose of the present study was to assess the possible sites which contribute to the nerve stimulation- and alpha-agonist-induced overflow of endogenous adenine nucleosides and nucleotides in vascular tissue. Particular attention was focused on the endothelium because it is known that endothelial cells have a high concentration of ATP and its metabolites. Segments of rabbit thoracic aorta, some denuded of endothelial cells by rubbing the lumen of the vessel, were incubated in organ baths and subjected to transmural nerve stimulation or stimulated with the alpha-1 adrenoceptor agonist methoxamine. A portion of the bathing solution was processed for the determination of norepinephrine by high-performance liquid chromatography with electrochemical detection and a portion for determination of ATP, ADP, AMP and adenosine by high performance liquid chromatography with fluorescence detection. Transmural stimulation led to a significant release of both norepinephrine and the adenine nucleosides and nucleotides in a ratio of 1 to 350. Removal of the endothelium did not change the release of norepinephrine but reduced the release of adenosine and its derivatives by 90%. Methoxamine also caused the release of adenosine and the adenine nucleotides which was reduced by 93% by removal of the endothelium. Thus, the endothelium seems to be a major source of transmural nerve stimulation and alpha-agonist induced overflow of adenosine and adenine nucleotides. The endothelium is not the exclusive source of these purine congeners, however. In the case of transmural stimulation there is approximately 10% of the total which is independent of the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319459 TI - Phorbol ester-induced stress and myosin light chain phosphorylation in swine carotid medial smooth muscle. AB - The mechanisms by which activators of protein kinase C (PKC) stimulate contractile responses in arterial smooth muscle is not known. In this study, we assessed the relative contribution of CA(++)-dependent and independent pathways in mediating phorbol ester-induced 20 kdalton myosin light chain (MLC) phosphorylation and force in medial smooth muscle strips from swine carotid artery. Phorbol 12,13-dibutyrate (PDB; 10(-7)M)-stimulated stress development was associated with a significant increase in the fraction of phosphorylated MLC, from 0.08 +/- 0.02 to 0.24 +/- 0.02 after 30 min of stimulation. Under conditions of Ca++ depletion, which normally do not support Ca++/calmodulin-dependent activation of myosin light chain kinase (MLCK) by physiological stimuli, PDB induced contractile responses were reduced significantly. However, after Ca2++ depletion, PDB (10(-6) M; 30 min) still caused an increase in MLC-phosphorylation from 0.10 +/- 0.02 at rest to 0.19 +/- 0.03. Preincubation with nifedipine (10( 7) M) had no significant effect on contractile responses to PDB, indicating that Ca++ influx through nifedipine-sensitive voltage channels did not contribute significantly to the observed Ca++ dependency of the PDB responses. Staurosporine (0.1-0.3 microM), a putative PKC inhibitor, significantly inhibited PDB-induced contractile and MLC phosphorylation responses. Tonic histamine (3 microM)- and KCl-induced contractile and MLC-phosphorylation responses were inhibited by the same concentrations of staurosporine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319460 TI - Comparison of two different arterial tissues suggests possible 5 hydroxytryptamine2 receptor heterogeneity. AB - A comparison of activities and affinities of several known and novel compounds in the isolated rat thoracic aorta (RA) and the rabbit femoral artery (RFA) was undertaken to evaluate these two tissues for use in screening for functional 5 hydroxytryptamine2 (5-HT2) receptor activity. Affinities for 5-HT and for ketanserin against 5-HT-elicited contractions in both vascular tissues suggested the presence of homogeneous 5-HT2 receptors with values consistent with other reported 5-HT2 receptor preparations. However, further studies showed compounds which exhibited either partial agonism in the RFA and competitive antagonism of 5 HT in the RA, or antagonism of 5-HT in both arteries with different affinities. Affinity constants calculated from the isolated vascular tissue studies were compared with affinity constants calculated for inhibition of [3H]ketanserin binding in the frontal cortices of both the rat and the rabbit. There were no significant differences between the pKi values in the rat and the rabbit cortical membranes or between these pKi's in either species and the pA2 values in the RA. Several of the affinities for both the partial agonists and the antagonists in the RFA were significantly different from the binding pKi and the pA2 values in the RA. These findings suggest identity between the [3H]ketanserin binding site in the cortices of both species and the 5-HT2 receptor in the RA; however, the contractile 5-HT receptor in the RFA, although showing some characteristics of a 5-HT2 receptor, is significantly different. We suggest that there may be functional subtypes of the vascular 5-HT receptor. PMID- 2319461 TI - Sch 37370: a potent, orally active, dual antagonist of platelet-activating factor and histamine. AB - Platelet-activating factor (PAF) and histamine are potent bronchospastic agents and possess additional properties such as induction of vasopermeability and activation of inflammatory cells that are consistent with their ability to mediate allergic and inflammatory responses. From a structural series with anticipated antihistamine activity, Sch 37370 (1-acetyl-4(8-chloro-5,6-dihydro 11H-benzo[5,6]cyclohepta[1,2- b]pyridine-11-ylidine)piperidine) has been identified as a dual antagonist of PAF and histamine in vitro and in vivo and has been compared with several selective antagonists of PAF and histamine. Sch 37370 selectively inhibits PAF-induced aggregation of human platelets (IC50 = 0.6 microM) and also competes with PAF binding to specific sites in membrane preparations from human lungs (IC50 = 1.2 microM). Sch 37370 blocks the binding of [3H]pyrilamine to histamine-H1 receptors in rat brain membranes. Administered i.v. to guinea pigs, Sch 37370 is an equipotent antagonist of PAF and histamine induced bronchospasm (ED50 = 0.6-0.7 mg/kg). Orally in guinea pigs, Sch 37370 is somewhat more effective against bronchospasms to histamine (ED50 = 2.4 mg/kg) than against PAF (ED50 = 4.1-6.0 mg/kg) or serotonin (ED50 = 9.6 mg/kg). Sch 37370 only weakly antagonizes methacholine-induced bronchospasm (ED50 = 51 mg/kg) and is completely inactive at 50 mg/kg against leukotriene C4 or substance P. Sch 37370 blocks hypotension in rats and a cutaneous reaction in monkeys induced by either PAF or histamine, as well as PAF-induced lethality in mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319462 TI - Intratubular albumin blunts the response to furosemide-A mechanism for diuretic resistance in the nephrotic syndrome. AB - An attenuated response to loop diuretics is a frequent observation in the nephrotic syndrome. To determine if the presence of albumin in renal tubular fluid attenuates diuretic response in normal rats, in vivo loop segment microperfusion was performed in normal rats at 20 nl/min with perfusates containing 6.0 microM furosemide in the presence and absence of 3.8 microM albumin. Compared to loop segments perfused without diuretic (control), furosemide reduced (P less than .001) fractional chloride uptake from 56 +/- 2 to 34 +/- 2%. After addition of albumin to furosemide perfusate, fractional loop chloride reabsorption was 45 +/- 1%; a value greater (P less than .01) than that observed in furosemide perfused loop segments, but less (P less than .05) than that observed in control loop segments. Albumin added to perfusate in the absence of furosemide had no effect on fractional loop segment chloride uptake. Addition of 1.7 microM immunoglobulin G to furosemide perfusate failed to attenuate furosemide response. Absolute loop segment chloride reabsorption demonstrated a similar pattern. Tubule fluid perfusion rates determined in vivo and loop segment fluid reabsorption were equivalent in all groups. Thus, albumin in renal tubule fluid attenuates the effect of furosemide on loop segment chloride reabsorption in the rat. This blunted response presumably occurs because of a reduction in the amount of pharmacologically active drug due to albumin-furosemide binding. Consequently, albumin-furosemide binding in the renal tubule may contribute to the diuretic resistance in nephrotic syndrome. PMID- 2319463 TI - Pharmacokinetics and disposition of the KS1/4 monoclonal antibody desacetylvinblastine hydrazide conjugate LY203725 in rats and monkeys. AB - The plasma pharmacokinetics of the monoclonal antibody-vinca conjugate KS 1/4 desacetylvinblastine hydrazide (DAVLB-hyd; [3H]LY203725) have been evaluated in rats (17 mg/kg) and monkeys (15 mg/kg) after i.v. dosing. Plasma concentrations of radioactivity 1 hr after dosing were higher in monkeys than in rats. The biphasic elimination of radioactivity in rats was characterized by half-lives (T1/2) of 10 and 143 hr, whereas the elimination of radioactivity in monkeys was characterized by T1/2 values of 11 and 66 hr. Plasma total antibody and radioactivity concentrations were similar within 6 (rat) and 24 (monkey) hr after dosing; however, total antibody concentrations were greater than radioactivity concentrations thereafter, indicating the presence of free antibody in the plasma. Plasma elimination T1/2 values and areas under the curve of total antibody in rats and monkeys were greater than those of radioactivity. The presence of free antibody implies the presence of free DAVLB-hyd; however, plasma concentrations of free DAVLB-hyd were at least 3 orders of magnitude less than those of radioactivity in both species. The T1/2 of free DAVLB-hyd in plasma of LY203725 dosed monkeys was 16 hr. Hydrolysis of the conjugate to yield free DAVLB hyd was observed upon incubation of conjugate with rat plasma in vitro. Administration of DAVLB-hyd to rats resulted in a rapid initial decrease in plasma DAVLB-hyd followed by a slower (T1/2 = 1.4 hr) elimination rate. Fecal excretion was the predominant mode of elimination of radioactivity in both rats and monkeys dosed with [3H]LY203725. PMID- 2319464 TI - Tolerance and physical dependence to a short-acting benzodiazepine, midazolam. AB - Midazolam is a new ultra short-acting benzodiazepine whose physical dependence properties have not been well characterized. Our laboratory has demonstrated previously that physical dependence to the long-acting chlordiazepoxide in the rat is inducible by a single intoxicating dose, whereas maximal dependence required chronically equivalent maximally tolerable dosing b.i.d. for 5 weeks. Based on the methods developed in our laboratory to quantify benzodiazepine intoxication and withdrawal, Trs were designed to evaluate midazolam's capacity to induce dependence in the rat after definable acute (120 mg/kg p.o.), sub-acute (120 mg/kg q.i.d. x 3 days) and chronic (120-180 mg/kg bid. x 5 weeks) dosing that was near maximally tolerable. A single dose of midazolam failed to produce withdrawal signs. Tolerance and dependence increased as a function of midazolam dose and duration of Tr. PMID- 2319466 TI - Factors affecting rabbit mesenteric artery smooth muscle sensitivity to calcium antagonists. AB - The sensitivity of rabbit isolated superior mesenteric artery to Ca++ antagonists was examined under various conditions. Relaxation dose-response curves for D600 or nifedipine were generated, and IC50 values were calculated. In the first series of experiments, D600 or nifedipine IC50 was found to be 20-25-fold greater for norepinephrine (NE, 5 microM) contraction than for 80 nM K+ contraction. Even when the tissues were depolarized with 80 mM K+ before NE contraction, D600 or nifedipine IC50 still remained significantly greater compared with 80 mM K+ alone and remained closer to that during NE alone. Also a protocol was designed to study NE-induced phasic contraction in EGTA-physiological salt solution (a functional indicator of intracellular Ca++ release) as well as NE-induced sustained contraction after readdition of Ca++. The effects of varying [K+]ex (0 80 nM range) on NE-induced [Ca++]i release as well as on the D600 IC50 for NE contraction was studied. Increasing [K+]ex was found to enhance NE-sensitive [Ca++]i release and lower the D600 IC50 for NE contraction. Thus, conditions causing an increase in the ability of NE to cause [Ca++]i release were associated with an increase in the sensitivity of NE contraction to D600. These data provide functional evidence that the receptor-agonist sensitive Ca++ influx process in vascular smooth muscle is not solely regulated by changes in membrane potential. Additional mechanisms, such as a modulatory role of [Ca++]i release, in this process are implicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319465 TI - The antiseizure activity of dihydropyridine calcium channel antagonists in the conscious rat. AB - By using a rat seizure model, a comparison of the antiseizure activity of 12 dihydropyridine calcium channel antagonists (administered i.c.v.) to their binding affinities for the neuronal site known to regulate L-type calcium channels was made. For these dihydropyridine calcium channel antagonists a correlation between physiologic activity and binding affinities would provide evidence that these agents exert their antiseizure actions via a mechanism involving a binding site that regulates L-type neuronal calcium channels. Despite i.c.v. administration, a parallel in antiseizure activity and binding affinities could not be demonstrated precisely, suggesting that the dihydropyridines may be exerting their antiseizure activity by more than just simple neuronal calcium channel blockade. PMID- 2319467 TI - Effect of dose on nicotine's reinforcing, withdrawal-suppression and self reported effects. AB - Seventy-eight smokers trying to quit were randomly assigned to 0-, 0.5-, 2- and 4 mg doses of nicotine gum and tracked for 9 months. In the 1st week of abstinence, self-administration of gum did not differ by dose (4 mg = 2 mg = 0.5 mg = 0 mg). Higher doses did not more effectively suppress withdrawal than lower doses nor induce more accurate nicotine identification (4 mg = 2 mg = 0.5 mg greater than 0 mg). Higher doses slightly increased ratings of adverse effects in the 1st week (4 mg greater than 2 mg greater than 0.5 mg greater than 0 mg). Over the next 6 months, the two higher doses appeared to support more gum self-administration than the two lower doses (4 mg = 2 mg greater than 0.5 mg = 0 mg) in the subsample of long-term quitters (n = 20). Our results suggest the dose-response curves differ for nicotine gum's reinforcing, withdrawal-suppression and self reported effects. PMID- 2319468 TI - Biliary excretion and conjugation of diacid angiotensin-converting enzyme inhibitors. AB - The metabolism and biliary excretion of the diacid angiotensin-converting enzyme inhibitors enalapril, lisinopril, perindopril and ramipril have been studied in an isolated perfused rat liver model. Inhibitors were presented to the livers at a dose of 100 micrograms. The hepatic clearance of lisinopril was very low (0.072 ml/min) and was hardly excreted into the bile. The clearances of enalapril, perindopril and ramipril were higher at 0.63, 0.87 and 9.9 ml/min, respectively, and were excreted into bile. The amounts of ester prodrugs excreted in bile were 4.0, 6.1 and 14%, respectively, whereas the diacid forms were excreted to the extent of 46, 27 and 71% of the administered dose, respectively, over 4 hr. Glucuronide metabolites were only detected in bile in significant concentrations for perindopril and ramipril. Base hydrolysis of the perfusate samples showed that lisinopril was not significantly metabolized to conjugates and that little metabolism of enalapril occurred other than rapid conversion to the diacid form. However, both perindopril and ramipril were extensively metabolized beyond the diacid form. These differences in hepatic handling can in part be explained by their octanol-buffer partition coefficients but may also be related to the introduction of a bicyclic ring in perindopril and ramipril which increases their ability to be metabolized and excreted into bile. These differences in hepatic handling of angiotensin-converting enzyme are likely to influence their clinical usefulness, particularly in renal and hepatic disease. PMID- 2319469 TI - Influences of stress on gastric alkaline secretion in rats. AB - Influences of restraint plus water-immersion stress on gastric alkaline response and mucosal blood flow were investigated in the rat. Under normal conditions, the stomach secreted alkali at the rate of approximately 1 microEq/15 min in the presence of omeprazole (60 mg/kg i.p.) and responded to mucosal acidification (1000 mM HCI for 10 min) by a significant rise of output (approximately 2.5 microEq/15 min), and the latter process was significantly blocked by indomethacin (5 mg/kg s.c.), quinacrine (100 mg/kg s.c.) and vasopressin (10 unit/kg/hr i.v.). Restraint alone decreased basal rates of HCO3- secretion but had no effect on acid-induced HCO3- output. Additional water-immersion stress further reduced alkaline secretion, totally abolished the increased HCO3- response to acid and significantly suppressed the increase of HCO3- output caused by 16,16-dimethyl prostaglandin E2 (3-30 micrograms/kg s.c.). During restraint stress mucosal blood flow was reduced only by 30% but after exposure to additional water-immersion, it further decreased to about 25% of normal values. Both indomethacin and quinacrine had no effect on mucosal blood flow, whereas vasopressin markedly reduced mucosal blood flow by about 80%. These results suggest that stress not only reduced basal rates of alkaline secretion in the stomach but also impaired the mucosal ability to increase HCO3- output in response to acid. These secretory disorders caused by stress may be attributed to both a decrease of mucosal blood flow and prostaglandin deficiency in the mucosa. PMID- 2319470 TI - Distinct coronary artery receptor systems for epidermal growth factor urogastrone. AB - In porcine (PCA) and bovine (BCA) coronary arterial strips, epidermal growth factor-urogastrone (EGF-URO) caused an endothelium-independent Ca-requiring contractile response that could not be attributed to the secondary release of agonists from neural elements. In these tissues, EGF-URO also potentiated the contractile actions of other agonists (prostaglandin F2 alpha, KCl or norepinephrine). Nonetheless, the responsiveness of the PCA and BCA preparations differed markedly in terms of 1) their sensitivity to indomethacin and dexamethasone (indomethacin and dexamethasone abrogated the PCA but not the BCA response), 2) their desensitization properties (the BCA rapidly desensitized, whereas the PCA did not) and 3) the order of potencies for EGF-URO and transforming growth factor-alpha (TGF-alpha) (in the PCA, EGF-URO was more potent than TGF-alpha, whereas in the BCA, the potency of TGF-alpha was greater than or equal to that of EGF-URO). Taken together our data document the presence of two distinct receptor signaling systems for EGF-URO in the PCA and BCA preparations, and our results support the hypothesis that distinct receptor subtypes for EGF URO may be present in these two tissues. PMID- 2319471 TI - O2-dependent hepatotoxicity due to ethylhexanol in the perfused rat liver: mitochondria as a site of action. AB - Toxicity of 2-ethylhexanol, a metabolite of diethylhexyl phthalate, was assessed in the perfused rat liver. Livers from starved rats were perfused with ethylhexanol (3 mM) dissolved in Krebs-Henseleit buffer (pH 7.4, 37 degrees C) saturated with 95% O2-5% CO2 in both the anterograde and retrograde direction. Following infusion of ethylhexanol, O2 uptake and ketone body formation were diminished by 50 and 80%, respectively, and cell damage, as assessed by the appearance of lactate dehydrogenase in the effluent perfusate, was apparent. Both inhibition of O2 uptake by ethylhexanol and the appearance of lactate dehydrogenase in the perfusate were dose-dependent. Only O2-rich upstream regions of the liver lobule were damaged as reflected by trypan blue uptake. Inhibition of O2 uptake by ethylhexanol was also reflected by a 60% decrease in the ATP/ADP ratio. Local rates of O2 uptake, measured using miniature electrodes placed on the liver surface, indicated that ethylhexanol only diminished O2 uptake in O2 rich upstream regions of the liver lobule regardless of the direction of flow. This phenomenon apparently can be explained by a direct effect of ethylhexanol on mitochondria in upstream regions since active state 3 rates of respiration were inhibited by ethylhexanol in isolated mitochondria. Ethylhexanol also caused a dose-dependent decrease in the mitochondrial membrane potential and an increase in the beta-hydroxybutyrate/acetoacetate (B/A) ratio. However, infusion of radical scavengers such as allopurinol, cianidanol and uric acid did not alter lactate dehydrogenase release due to ethylhexanol. Thus, the toxicity of ethylhexanol in the liver is dependent on local O2 tension and mitochondrial are primary targets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319473 TI - Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine receptor. AB - Experiments were undertaken to characterize pharmacologically a neuronal receptor to 5-HT in guinea pig ileum. Segments of longitudinal muscle myenteric plexus preparations were treated with phenoxybenzamine and exposed to submaximal electrical field stimulation to evoke the cholinergically mediated "twitch" response. The ability of 5-HT to enhance the submaximal twitch response was investigated. Results using several antagonists (metergoline, spiperone, cyanopindolol, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide, N-hexanoyl 5-hydroxytryptophyl-5-hydroxytryptophan amide, ICS 205-930, GR 38032F, MDL 72222 and cocaine) indicate that 5-HT (3 X 10(-10) to 1 x 10(-7) M) agonizes a novel 5 HT receptor site distinct from the 5-HT1, 5-HT2, 5-HT3 and 5-HT1P subtypes as well as the M receptor. The receptor site is located neuronally and is characterized positively by a low affinity for ICS 205-930 (pA2 = 6.5 vs. 5-HT) and by the following order of agonist potency: 5-HT greater than 5 methoxytryptamine greater than BRL 24924 greater than alpha-methyl-5 hydroxytryptamine greater than zacopride = cisapride = 5-carboxamidotryptamine. Agonist-independent pA2 estimates for ICS 205-930 (6.3-6.6) suggest a single site of agonism. 2-Methyl-5-hydroxytryptamine and 5-hydroxyindalpine were inactive at 1 x 10(-5) M either as agonists or antagonists. Thus, the receptor site exhibits a pharmacological profile similar to that characterizing the recently described 5 HT4 [corrected] receptor. Unlike Gaddum's M receptor, which equates with the 5 HT3 [corrected] receptor, the putative 5-HT4 [corrected] receptor site exhibits a higher sensitivity to agonism by 5-HT and is resistant to antagonism by cocaine. PMID- 2319472 TI - Enkephalinergic and GABAergic modulation of motor activity in the ventral pallidum. AB - Injection of the mu-opioid receptor agonist, Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAMGO), produced a dose-dependent increase in horizontal motor activity after injection into the ventral pallidum or substantia innominata (VP/SI) of the rat. INjection of the delta-opioid receptor agonist, [D-Pen2,5]-enkephalin, produced a markedly reduced motor stimulant action, as did injection of DAMGO outside the VP/SI. Injection of the GABAA receptor antagonist, bicuculline, or the antagonist of the GABAA chloride channel, picrotoxin, also produced a dose-related elevation in horizontal motor activity. In contrast, the GABAB receptor antagonist, phaclofen, was without effect. The motor stimulant actions of both DAMGO and picrotoxin were attenuated by pretreatment in the VP/SI with the GABAA receptor agonist, muscimol. In contrast, pretreatment with the opioid receptor antagonist, naloxone, abolished only the actions of DAMGO on motor activity. These data demonstrate that motor activity can be regulated in the VP/SI by mu-opioid and GABAA neurotransmission, and that the response to mu-opioids can be modulated by GABAergic transmission. PMID- 2319474 TI - Covalent binding of phenytoin to protein and modulation of phenytoin metabolism by thiols in A/J mouse liver microsomes. AB - The role of thiols (nonprotein and protein) in the metabolic activation of phenytoin was examined. In vitro phenytoin covalent binding and metabolite formation were determined in hepatic microsomes from A/J mice. Covalent binding of a phenytoin-reactive intermediate to microsomal protein was linear with respect to time, protein concentration and phenytoin concentration. Covalent binding was inhibited by inhibitors of cytochrome P-450. Inducers of cytochrome P 450 enhanced phenytoin covalent binding as follows: phenobarbital greater than 3 methylcholanthrene greater than saline-treated controls. Low molecular weight thiols (GSH, cysteine and cysteamine), a thiol generator (methylthiazolidine carboxylate), and thiol modifying agents (N-ethylmaleimide, mercuric chloride and diamide) significantly inhibited covalent binding. Amino acids other than cysteine did not decrease the covalent binding. Formation of the metabolites, para-hydroxyphenytoin and phenytoin dihydrodiol, was greater following preincubation with GSH or cysteine. In summary, protein thiol groups appear to be important sites for in vitro covalent binding of a reactive intermediate of phenytoin. These data suggest glutathione may protect membrane-bound enzymes responsible for phenytoin metabolism from attack by an electrophilic or free radical reactive intermediate of phenytoin and GSH may inactivate a phenytoin reactive metabolite by formation of a putative glutathione conjugate. PMID- 2319475 TI - Comparison of spectrophotometric and biological assays for nitric oxide (NO) and endothelium-derived relaxing factor (EDRF): nonspecificity of the diazotization reaction for NO and failure to detect EDRF. AB - Endothelium-derived relaxing factor has been tentatively identified as nitric oxide (NO) partially on the basis of chemical assays. In the present study, saline solutions that were either bubbled continuously for 30 min with NO (NO/X) or prepared using 25 ml of NO/ml (NO/25) produced equivalent relaxations of segments of rabbit aorta which had the endothelium removed. NO solutions prepared using 0.1 ml of NO/ml (NO/0.1), and 3 mM sodium nitrite (NO2-) were significantly (P less than .05) less potent vasodilators than NO/X and NO/25 (order of potency: NO/X = NO/25 greater than NO/0.1 greater than NO2-). A novel automated method was developed to monitor nitrogen oxides using continuous-flow spectrophotometric detection (diazotization reaction). The absorbance readings for the solutions were NO/X greater than NO/25 = NO/0.1 = NO2-. Argon purging of NO/X, NO/25 and NO/0.1 solutions significantly (P less than .05) reduced (44-100%) the bioactivity of these solutions in inverse proportion to the initial volume of NO used in their preparation. In contrast, the absorbance values were unchanged, indicating that the chemical assay was not correlated with the bioassay. Varying the duration of NO gassing (1-30 min) significantly (P less than .05) increased the absorbance values, while having no effect on the vascular relaxations, elicited by the solutions. The diazotization assay did not detect nitrogen oxides released from cultured endothelial cells by bradykinin, ATP, or A23187, whereas the bioassay readily detected endothelium-derived relaxing factor release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319476 TI - Prostaglandin F2 alpha inhibits acidification in H(+)-secreting epithelia. AB - The role of prostaglandins in the regulation of acidification mechanisms in H(+) secreting epithelia has been investigated in the abdominal skin of the southern leopard frog, Rana pipiens. Exogenous administration of prostaglandin (PG) E2 and PGF1 alpha (10(-7) M) to the serosal media of paired skins mounted in modified Ussing chambers showed no significant alteration on H+ excretion rates. PGF2 alpha exhibited a dose-dependent inhibition of acidification in both the mucosal and serosal media of animals in normal acid-base states. The ED50 was determined to be 5 X 10(-8) M. Animals placed in an NH4Cl-induced chronic metabolic acidosis demonstrated enhanced H+ excretion from normal which was inhibited by PGF2 alpha (10(-8) M). Frogs treated with ibuprofen (30 mg/kg/day for 3 days) stimulated mucosal acidification to a magnitude similar to the chronic metabolic acidosis animal, and this was inhibited by PGF2 alpha (10(-8) M) during the recovery phase. PGF2 alpha produced effects on both the mucosal proton excretion system and the serosal Na+/H+ exchanger mechanism. PGF2 alpha appears to function in this H(+)-secreting epithelia to maintain a low basal H+ excretion rate and to regulate intracellular pH. PMID- 2319477 TI - Smoked marijuana effects on tobacco cigarette smoking behavior. AB - The effects of marijuana smoke exposure on several measures of tobacco cigarette smoking behavior were examined. Eight healthy adult male volunteers, who smoked both tobacco and marijuana cigarettes, participated in residential studies, lasting 10 to 15 days, designed to measure the effects of marijuana smoke exposure on a range of behavioral variables. Tobacco cigarettes were available throughout the day (9:00 A.M. until midnight). Each day was divided into a private period (9:00 A.M. to 5:00 P.M.), during which subjects were socially isolated, and a social period (5:00 P.M. to midnight), during which subjects could interact. Under blind conditions, subjects smoked placebo and active marijuana cigarettes (0%, 1.3%, 2.3%, or 2.7% delta 9-tetrahydrocannabinol) four times daily (9:45 A.M., 1:30 P.M., 5:00 P.M. and 8:30 P.M.). Each subject was exposed to both placebo and one active dose over 2- to 5-consecutive-day intervals, and dose conditions (i.e., placebo or active) alternated throughout the study. Active marijuana smoking significantly decreased the number of daily tobacco smoking bouts, increased inter-bout intervals and decreased inter-puff intervals. Marijuana decreased the number of tobacco smoking bouts by delaying the initiation of tobacco cigarette smoking immediately after marijuana smoking, whereas decreases in inter-puff intervals were unrelated to the time of marijuana smoking. No consistent interactions between marijuana effects and social or private periods (i.e., time of day) were observed. PMID- 2319478 TI - Differential development of tolerance to the effects of d-amphetamine and fenfluramine on food intake in baboons. AB - Food intake of six adult male baboons (Papio cynocephalus anubis) was monitored during daily 22-hr experimental sessions. Food was available under a chain schedule with two components. After completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the second "consumption component," during which each response produced a 1 g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. Complete dose-response functions for amphetamine and fenfluramine were determined before, during and after a period of repeated administration of each drug. On the first day of repeated administration both drugs decreased intake during both the first 8 hr and the entire session to 65% of baseline. Total intake returned to 93% of baseline during repeated amphetamine, but only to 76% of baseline during repeated fenfluramine. There was no recovery of intake, however, during the first 8 hr of the session. Baboons given repeated amphetamine were tolerant to the food intake decreasing effects of acute amphetamine, but not acute fenfluramine. Baboons given repeated fenfluramine did not develop tolerance to the effects of fenfluramine or amphetamine on food intake. The absence of cross-tolerance or increased sensitivity between amphetamine and fenfluramine suggests that although both serotonergic and dopaminergic systems are involved in feeding, they can influence food intake independently. PMID- 2319480 TI - Doxorubicin blocks the increase in intracellular Ca++, part of a second messenger system in N1E-115 murine neuroblastoma cells. AB - Exposure of differentiated N1E-115 murine neuroblastoma cells, microinjected with the Ca(++)-sensitive photoprotein aequorin, to doxorubicin for 1 hr, but not for 2 min, produced a reversible block of the rise in intracellular free Ca++ [( Ca++]i) produced by histamine. The resting level of [Ca++]i was increased from 0.23 to 1.22 microM (P less than 0.05) by 10(-4) M histamine. After exposure to 10(-6) M doxorubicin for 1 hr, histamine increased [Ca++]i to only 0.34 microM (P less than 0.05 compared to the histamine alone value). Doxorubicin exposure for 1 hr completely blocked the increase in inositol trisphosphate caused by histamine. There was no block by doxorubicin of the release of intracellular Ca++ after microinjection of the cells with inositol 1,4,5-trisphosphate. Based on the results from studies with differentiated N1E-115 neuroblastoma cells doxorubicin may: 1) block the histamine-induced rise in [Ca++]i by decreasing synthesis of inositol polyphosphates, 2) block plasma membrane Ca++ channels that allow entry of extracellular Ca++ in response to histamine and/or 3) prevent recovery of histamine receptors after desensitization. PMID- 2319479 TI - Low-dose caffeine discrimination in humans. AB - A novel drug discrimination procedure was used to study the discriminability and subjective effects of caffeine in seven human volunteers who abstained from dietary sources of caffeine. Daily sessions involved p.o. ingestion of two capsules sequentially, one of which contained caffeine and the other placebo, under double-blind conditions. Each day subjects attempted to identify and were later informed which capsule contained caffeine and which contained placebo. All subjects acquired rapidly the initial discrimination (100 or 178 mg vs. placebo). Examination of progressively lower caffeine doses showed that accuracy and ratings of confidence in accuracy were increasing functions of dose. There were individual differences in the lowest discriminable dose: three subjects discriminated 56 mg, three discriminated 18 mg and one discriminated 10 mg. Discrimination accuracy was usually higher after the second capsule than after the first capsule. All subjects indicated that they believed that they made the discrimination predominantly on the basis of central effects of caffeine vs. placebo, such as changes in mood and socializing. Compared to placebo, 100 mg of caffeine increased ratings of alertness, well-being, social disposition, motivation for work, concentration, energy and self-confidence and decreased ratings of headache and sleepiness. This dose of caffeine also produced a large increase in a measure of "euphoria." The present study documents biological activity of caffeine at lower doses than heretofore recognized. The general approach to investigating the effects of low drug doses may have broad application in human psychopharmacology research for characterizing other subtle psychotropic effects. PMID- 2319482 TI - Rehabilitation R&D progress reports 1989. PMID- 2319481 TI - Serotonin1c receptor reserve in choroid plexus masks receptor subsensitivity. AB - This paper tests the hypothesis that spare serotonin 5-HT1c receptors are present in the rat choroid plexus and explores the possible influence of such sites on the adaptive regulation of the 5-HT1c receptor. The consequences of partial receptor inactivation were compared for the natural agonist 5-HT and the putative partial agonists trifluoromethylphenylpiperazine (TFMPP) and (+)-lysergic acid diethylamide (LSD). These studies showed approximately 50% reserve of 5-HT1c receptors in the rat choroid plexus. The calculated KA for 5-HT obtained by partial irreversible inactivation was 36 nM. Phenoxybenzamine reduced the maximum response elicited by TFMPP and LSD, without shifting the EC50 values, consistent with the interpretation that TFMPP and LSD are partial agonist at the 5-HT1c receptor in rat choroid plexus. The KA of TFMPP and LSD was 0.16 microM and 9 nM, respectively. Quantitative analysis of percentage of receptor occupancy vs. percentage of maximum response showed that 5-HT occupied only 70% of the receptors to give a maximum response, whereas a linear relationship between percentage of occupancy and response was found for TFMPP. These differences had functional consequences as demonstrated in studies of regulation of the 5-HT1c receptor. Chronic administration of the 5-HT agonist quipazine produced a 32% loss of 5-HT1c binding sites in the choroid plexus, with no change in the 5-HT induced phosphoinositide hydrolysis response. This dissociation between binding and function is likely explained by the receptor reserve that exists for the 5 HT1c receptors. Consistent with this interpretation, the TFMPP-induced phosphoinositide hydrolysis signal was reduced to the same extent as the loss of binding sites. These results show that the 5-HT1c receptor in the choroid plexus adapts predictably to chronic receptor activation and suggest the possibility that the paradoxical regulation that has been described for other 5-HT receptors might be explained partially by the unrecognized existence of receptor reserve. PMID- 2319483 TI - Contrast in neostigmine-induced changes in spontaneous activities and evoked muscle potentials in rat medial gastrocnemius and soleus muscles. PMID- 2319484 TI - Examining teachers' perceptions of children's support systems. AB - Teachers of 94 youth evaluated the functionality of their students' support systems by completing the Personal History Inventory for Children (Parish & Wigle, 1985). An analysis of variance revealed significant main effects due to students' family structure, gender, and birth order. Specifically, youth from divorced nonremarried and divorced remarried families experienced more dysfunctional support systems than youth from intact families. Further, boys were found to be at more risk than girls, and later borns were found to experience more support system failure than firstborns. PMID- 2319485 TI - Surviving and coping with loneliness. AB - Content analysis of 526 verbatim reports of loneliness revealed both helpful and nonhelpful coping strategies. The helpful strategies were grouped into three clusters that represent three distinct phases of the coping process. Eleven factors were subsumed under the three clusters. Four additional factors comprised the cluster of destructive and nonbeneficial coping strategies. The present study highlights the complexity and variety of coping strategies as well as the frequency with which they are used and their utility in helping people to survive loneliness and alienation. PMID- 2319486 TI - Sphaerospora ictaluri n. sp. (Myxosporea: Sphaerosphoridae) observed in the kidney of channel catfish, Ictalurus punctatus rafinesque. AB - Sphaerospores were found in the kidneys of alevin channel catfish (Ictalurus punctatus) from a farm in Central California. Multicellular developmental stages, similar to C-blood protozoans described for Sphaerospora spp. from cyprinid fishes, were observed in circulating blood and numerous tissues. Upon a 2nd examination of the same population of fish 10 days later, sporogonic stages were seen developing into mature sphaerospores in the lumina of the kidney tubules. Sporogenesis was asynchronous with simple unicellular stages adjacent to more complex forms with developing polar capsules and valves. Only one elliptical spore (5.6 microns in width, 6.5 microns in thickness by 5.8 microns in length) developed within the surrounding pseudoplasmodium. Thin valves surrounded two sporoplasm cells and two subspherical polar capsules (1.7 x 1.9 microns) which contained a polar filament with four to five turns. The blood stages of the Sphaerospora sp. described here are similar to the trophozoites seen in channel catfish with proliferative gill disease (PGD). Early stages of PGD also observed in the same population of channel catfish containing developmental and sporogonic stages of this newly recognized Sphaerospora sp. may suggest a causal relationship between this new myxosporean and the gill disease. PMID- 2319487 TI - Trypanosoma acomys (Wenyon, 1909): continuous culturing with a mouse fibroblast cell-line (A9). AB - The continuous culturing of Trypanosoma acomys in the presence of a murine areolar-adipose cell line (A9) was possible for the 1st time. The trypanosomes were cultured at 37 degrees C with A9 in DMEM supplemented with 20% heat inactivated fetal bovine serum, using an initial inoculum from primary cultures of lung or blood clots from infected spiny mice. The cultures were maintained for 115 days and underwent 15 passages before termination and cryopreservation. Using this culture system T. acomys subcultures were initiated from 3 different initial inocula (3 x 10(4), 1.5 x 10(5) and 7.4 x 10(5) parasites/ml) and growth curves revealed that the lowest inoculum gave the best growth pattern. This inoculum yielded a population doubling time of less than 12 h for 4 days, a high peak density of 7 x 10(6) parasites/ml and the most gradual decline compared to the other 2 inocula. Rosetting epimastigotes and nests of amastigotes were observed in close association with the feeder layer cells. Epimastigotes were the most predominant form in culture supernatants but other morphological forms observed included trypomastigotes and sphaeromastigotes. PMID- 2319488 TI - Analysis of Chlamydomonas reinhardtii histones and chromatin. AB - Chromatin spreads made from isolated nuclei of the unicellular green alga Chlamydomonas reinhardtii show the beaded fibers typical of eukaryotic polynucleosomes. Micrococcal nuclease digestions confirmed the presence of nucleosomes with a repeat length of 189 base pairs, essentially the same as typical mammalian cells. Basic nuclear proteins extracted from isolated nuclei or chromatin with 1 M calcium chloride and 0.3 M hydrochloric acid are resolved into seven major components by electrophoresis in the presence of sodium dodecyl sulfate (SDS). These seven components were subjected to qualitative peptide mapping with V8 protease on SDS gels for comparison with the major histone components of calf thymus. Finally, the C. reinhardtii basic nuclear proteins were fractionated by reversed phase high performance liquid chromatography and their amino acid composition determined. From these studies, we conclude that C. reinhardtii has a full complement of the five histones with properties very similar to those of both higher animals and higher plants. PMID- 2319489 TI - Effect of extracellular ions on motility and cell entry in Toxoplasma gondii. AB - Toxoplasma gondii tachyzoites were quiescent in mouse peritoneal fluid or in K2SO4 buffer at pH 8.2. They became consistently motile when K+ was replaced by other monovalent or divalent cations at a constant pH (pH = 8.2). They also became motile when Cl- was substituted for SO4(2-). Nitrate or SCN-, can also be substituted for Cl- to a certain extent. Tachyzoites showed independent movement for more than 15 min in KCl, and for about 5 min in the other buffers at pH 8.2 after which they were exhausted and stopped. These tachyzoites could not then be further stimulated to motility by renewal of the suspension buffer. Infection of monolayer cells was demonstrated only with parasites which were motile during inoculation. The highest infectivity was thus obtained either with freshly collected tachyzoites or with those preincubated in K2SO4 buffer for 30 min at 37 degrees C at alkaline pH and thus not yet exhausted for motility. Approximately 34 to 38% of these latter organisms were seen to enter cells when they were inoculated into cultures immediately after being resuspended in MEM for 30 min at 37 degrees C. Conversely, those whose motility had been exhausted by the preincubation in buffers other than K2SO4, pH 8.2 could not enter monolayer cells. Additionally, parasites were unable to enter cells when inoculated into cultures in K2SO4 buffer at alkaline pH; instead they remained quiescent on the surface of the monolayer cells, suggesting that Toxoplasma enters the host cells by active invasion. PMID- 2319490 TI - Intracellular development of Enterocytozoon, a unique microsporidian found in the intestine of AIDS patients. AB - Enterocytozoon was 1st described in 1985, in an AIDS patient with intestinal malabsorption and diarrhea. Since then, additional cases of infection with this organism have been observed, but only in individuals with AIDS and malabsorption. Intestinal tissue biopsies were obtained from a 45-year-old man prior to AIDS diagnosis, again nine months later and then at autopsy two months later. When the biopsies were examined electron microscopically, both sets contained the microsporidian parasite. However, the 2nd intestinal biopsy, when wasting was much more severe, contained infection in almost every small intestinal enterocyte examined. The parasite was actively developing, allowing us to detail its life cycle. The parasite is apansporoblastic, polysporous and has characteristics not previously reported in the Microsporida: (1) an electron lucent inclusion not usually seen in Microsporida is prominent and always present; (2) extremely elongated sausage-shaped nuclei occur in the proliferative phase of parasite development; (3) the polar tube development uniquely involves the production of electron dense discs, yet results in the formation of a typical spore; and (4) polar tube development occurs prior to the final division of the multi-nucleate sporont. On the basis of these characteristics, we are placing this genus in a new family, Enterocytozoonidae, n. fam. PMID- 2319492 TI - Nolleria pulicis n. gen., n. sp. (Microsporida: Chytridiopsidae), a microsporidian parasite of the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae). AB - A new species of microsporidium, Nolleria pulicis, is described and named here from the cat flea, Ctenocephalides felis. The genus Nolleria is created and placed within the family Chytridiopsidae. The family is slightly modified to accommodate certain features of intracellular development seen in N. pulicis, which is otherwise very similar to other species in the family Chytridiopsidae. Sporulation is described from ultrastructural analysis of infected midgut epithelial cells of adult C. felis. The term "multiple division by vacuolation" is proposed for describing sporogony as it occurs in this species and certain related species of microsporidia. The probable mode of transmission and apparent absence of merogony are discussed. PMID- 2319491 TI - Identification of sporozoite surface proteins and antigens of Eimeria nieschulzi (Apicomplexa). AB - Sodium dodecyl sulfate polyacrylamide gel electrophoresis, immunoblotting, lectin binding, and 125I surface labeling of sporozoites were used to probe sporozoites of the rat coccidian, Eimeria nieschulzi. Analysis of silver stained gels revealed greater than 50 bands. Surface iodination revealed about 14 well labeled, and about 10 weakly labeled but potential, surface proteins. The most heavily labeled surface proteins had molecular masses of 60, 53-54, 45, 28, 23 24, 17, 15, 14, 13, and 12 kD. Following electrophoresis and Western blotting, 2 of the 12 125I labeled lectin probes bound to two bands on the blots, which collectively indicated that two bands were glycosylated. Concanavalin A (ConA) specifically recognized a band at 53 kD, which may represent a surface glycoprotein, and a lectin derived from Osage orange (MPA) bound to a single band at 82-88 kD, that may also be a surface molecule. Immunoblotting using sera collected from rats inoculated orally with oocysts, as well as sera from mice hyperimmunized with sporozoites, revealed that many surface molecules appear to be immunogenic. PMID- 2319493 TI - Looking to the future: exploring community approaches to dental health. 70th anniversary symposium proceedings. October 26-28, 1988, Durham, North Carolina. PMID- 2319494 TI - What should dental public health be in the future? AB - Many factors contribute to a successful dental public health program. Each of these must be developed and constantly cultivated to ensure the continuation and improvement of the program. In looking to the future, dental public health must remember its commitment to the community as its patient and its long history of public/private partnership. To best serve the citizens of the state, participants in this partnership must carefully consider which activities are appropriate for the different providers of dental services. PMID- 2319495 TI - Excerpts from presentation on epidemiologic data and changing demographics. AB - Dental surveys provide epidemiologic and sociodemographic data useful for program planning, implementation, and evaluation. Dental public health decisions in North Carolina have been based on statewide oral health surveys. Results from the 1986 87 North Carolina School Oral Health Survey and a comparison of these data to previous survey results and to recent national estimates of oral disease provide a basis for the discussions and deliberations during the symposium. PMID- 2319496 TI - National oral health objectives for the year 2000. AB - The recent Institute of Medicine report on the future of public health is stimulating widespread discussion of the appropriate scope, direction, and means of ensuring the nation's health through public health efforts. Concurrently, the nation is in the process of establishing national disease prevention and health promotion objectives for the year 2000. This is a natural progression from the broad health promotion and disease prevention activities of the past, the 1990 Health Objectives for the Nation, and the Model Standards for Community Preventive Health Services. It is timely for North Carolina, as it celebrates past accomplishments of the state dental public health program, to consider alternative approaches to planning for the public's oral health. The year 2000 process, a national grass-roots initiative, may be a useful model for individual states to adopt. Beyond identifying specific oral health concerns, the year 2000 process offers a number of functional values: the opportunity to educate a wide audience, prioritization of state oral health concerns, identification of gaps in current programs and surveillance, and the opportunity to create an effective constituency among those individuals and institutions in the best position to bring about change. PMID- 2319497 TI - Summary from group discussions: what should dental public health be? The issues, constituencies, and priorities of the future and how to get to the "should"? strategies and interventions using the community approach. PMID- 2319498 TI - Anticipating the future and change. AB - As in all of medicine, there are basic assumptions underlying the present system of dental education and delivery. These basic assumptions are facing challenges due in part to the marked reduction in the incidence of caries and the development of more effective therapies. This current period of time is described as an era of true change, rather than the mere modification of existing technology. Changes are going to occur in a number of areas. The move will be from government to private, from small to large, from generalist to specialist. Since change is inevitable, one can learn about and prepare for the stress of change, the changes happening now, and how to adapt to change. Although many changes are beyond the individual's control, their occurrence may be beneficial. PMID- 2319499 TI - The Ramstein airshow disaster. AB - In August 1988 an aircraft of the Italian aerobatic display team fell into the spectator enclosure at the Ramstein Airshow, causing over 500 casualties. The survivors were triaged, treated and evacuated from Ramstein within 96 minutes. The speed and efficiency of this evacuation was a result of prior planning, thorough training, medical reinforcement, co-operation with other agencies and the availability of an abundance of vehicles for both air and road evacuation. Not suprisingly, though, problems did occur, especially with communications, casualty identification and documentation. PMID- 2319500 TI - Assessing injury severity during general war. Will the Military Triage system meet future needs? AB - The injuries likely to occur during a future general war will differ in severity and number from those experienced during recent short campaigns, terrorist incidents and natural disasters. If general war should break out in Europe, casualty numbers will lean towards the First World War rather than the Second in scale. Medical assets can expect, at least temporarily, to be overwhelmed with casualties. To deal with this problem, casualty management will be staged through five echelons or lines of medical support. The principal problem that will face medical attendants at the forward lines will be the sorting of casualties by priority so that those unable to tolerate delay in treatment will be evacuated rapidly before the less severely injured. Sorting will be achieved by the application of a crude scoring system known as Military Triage. We examine this concept and discuss its likely effectiveness in a scenario characterised by limited medical resources and a high flow of casualties. With the widespread introduction of modern and complex injury severity scoring systems into civilian trauma practice it is timely to examine their potential role in augmenting or replacing the current Military Triage system. PMID- 2319501 TI - The Army Personnel Research Committee (APRC) and the Army. PMID- 2319502 TI - Haemopneumothorax and mediastinal emphysema. A dramatic rescue in the South Atlantic. AB - Spontaneous haemopneumothorax has a high mortality and morbidity which increase if the treatment is delayed. A patient with tension haemopneumothroax and mediastinal emphysema, rescued from a fishing boat in the middle of the South Atlantic, responded well to conservative treatment, despite delay in initiating treatment. The clinical presentation and management are discussed. PMID- 2319503 TI - The dangers of electrocardiography in general practice. AB - The use of the electrocardiograph by general practitioners was studied by scrutiny of 100 successive referrals to the Department of Clinical Electrophysiology. 31% of referrals were on patients with chronic, recurrent chest pain and a further 13% were on patients with a recent episode of acute chest pain. The ECG is of limited diagnostic value in patients with chest pain, and it may be both misleading and time-wasting when used inappropriately by general practitioners. PMID- 2319504 TI - A retrospective study of all low birth-weight preterm babies born in BMH Rinteln between 1980-1989. AB - A retrospective study was undertaken of all preterm babies born in BMH Rinteln between 1980-88 weighing less than 2500g. The total proportion of low birth weight babies was 7% and 58% of these were preterm (454 babies). Sixty per cent of women presented after the spontaneous rupture of membranes or in established labour. Conservative management of ruptured membranes, whilst not leading to life threatening sepsis, did not significantly prolong pregnancy. Sixteen percent of the babies were very low birth weight (under 1500g). Delivery of these infants by Caesarean section when presenting by the breech improved survival, although this was not statistically significant. Thirty percent of all babies were delivered by Caesarean section before 36 weeks, reflecting obstetric emergencies in the mother which predisposed to preterm delivery. Neonatal survival depended on both gestational maturity and birth weight and was not significantly better in babies who were low birth weight for gestational age. These infants however represented 75% of the still-births and congenital abnormalities. Sixty percent of the mothers smoked and 50% had other identifiable risk factors for preterm delivery; 20% of the multiparous patients had previously experienced a perinatal death, preterm delivery or had a baby with intra-uterine growth retardation. It is suggested that preterm delivery is a significant problem in an Army population despite full employment, adequate housing and comprehensive medical care. Attempts to stop labour are unlikely to be successful. Effort should be made antenatally to identify those women who may be at risk of "idiopathic" preterm labour, as patient education programmes have been shown to decrease the incidence. PMID- 2319505 TI - 'Top cover neuropathy'--transient brachial plexopathy due to body armour. AB - Two cases of partial lesions of the brachial plexus (brachial plexopathy) occurring in soldiers wearing body armour are described. This is an occupational hazard which has not been reported before. PMID- 2319506 TI - Management of sucking chest wounds. PMID- 2319507 TI - Management of sucking chest wounds. PMID- 2319508 TI - Whatever happened to AMD research project 247? PMID- 2319509 TI - Mitral valve prolapse. PMID- 2319510 TI - Operation Nightingale: the role of BMH Dharan following the 1988. Nepal earthquake, and some observations on Third World earthquake disaster relief missions. AB - Following a large earthquake in Nepal, the experience of a small hospital in dealing with the resulting mass casualties is described. The value of pre planning and effective triage of the injured is stressed, and aspects of surgical and medical care specific to earthquake victims discussed. Clinical and administrative challenges encountered in mounting a major relief exercise in a Third World setting are also described. frequent exercising of military hospitals and personnel in handling mass casualties is an applicable to civilian natural catastrophies as to battlefield medical support. PMID- 2319511 TI - Beta-lactamase inhibition: therapeutic advances in obstetrics and gynecology. A symposium. PMID- 2319512 TI - Development of beta-lactamase inhibitors. AB - The resistance of bacteria to beta-lactam antibiotics was first associated with the production of the enzyme beta-lactamase as long ago as 1940. Since then, increasing numbers of beta-lactamase-producing bacteria capable of inactivating penicillins and cephalosporins have been isolated clinically. One approach to the problem posed by beta-lactamase-producing bacteria has been to seek substances that function as inhibitors of beta-lactamase and that can be used to protect beta-lactam antibiotics from destruction by the bacterial enzymes. The first clinically available inhibitor was clavulanic acid, a metabolite of Streptomyces clavuligerus that was identified in a screening program for naturally occurring beta-lactamase inhibitors. Clavulanic acid is a potent inhibitor of many bacterial beta-lactamases and has been formulated with amoxicillin and ticarcillin to produce broad-spectrum antibiotic combinations active against beta lactamase-producing bacteria. After the discovery of clavulanic acid, various compounds have been reported to function as inhibitors of bacterial beta lactamases, but only sulbactam and its prodrug, sultamicillin, have become available commercially. The success of clavulanic acid has confirmed beta lactamase inhibitors as one solution to the problem of antibiotic-resistant bacteria. PMID- 2319513 TI - In vitro anaerobic data on ticarcillin/clavulanate. A review of an ongoing survey. AB - Although a number of new antimicrobial agents described as "broad spectrum" have been introduced during the past several years, it should be recognized that each of them has its own unique spectrum of activity, strengths and weaknesses that define its appropriate clinical use. This report reviews the comparative susceptibility data on 495 bacterial isolates obtained from obstetric and gynecologic patients and on 522 Bacteroides fragilis group isolates. Susceptibility testing was conducted with broth microdilution using twofold dilutions of antimicrobials. The overall minimal inhibitory concentrations-90 (MIC90) for the 495 isolates were very low, and few resistant isolates were found. The MIC90 for cefotetan was 16 times greater than that for ticarcillin/clavulanate and ampicillin/sulbactam. Cephalosporins showed good activity against anaerobic cocci but variable activity against anaerobic gram negative rods. A relatively high percentage of B fragilis group isolates were also resistant to clindamycin. The addition of 2 mg/mL of clavulanate to ticarcillin caused a 4- to 32-fold decrease in the MIC90 for various Bacteroides species. Less than 2% of the strains tested were resistant to clavulanate plus ticarcillin or amoxicillin. These results suggest that monotherapy with such agents could replace combination antibiotic therapy for mixed obstetric and gynecologic infections. PMID- 2319514 TI - Implications of beta-lactamase-inhibitor combinations. AB - Resistance of many species of bacteria to beta-lactam antibiotics is mediated via inactivation by beta-lactamase. Beta-lactamase inhibitors irreversibly bind to beta-lactamases and thus can prevent the destruction of active beta-lactam antibiotics. In the United States three beta-lactam-antibiotic/beta-lactam inhibitor combinations are commercially available--the orally absorbed amoxicillin/clavulanic acid (A/C), the parenteral formulations of ampicillin/sulbactam (A/S) and ticarcillin/clavulanate (T/C). In a multicenter study that focused on T/C, the in vitro activity of amoxicillin (AMOX), ampicillin (AMP) and ticarcillin (TIC) against Neisseria gonorrhoeae and Haemophilus influenzae was obliterated when beta-lactamase-positive strains were tested, but all tested strains were susceptible to the antibiotics in combination with their respective beta-lactamase inhibitors. Clavulanic acid improved the activity of TIC against most species of Enterobacteriaceae but not against those Enterobacteriaceae that elaborate type I beta-lactamase or against non Enterobacteriaceae gram-negative bacilli (except for Pseudomonas maltophilia). Staphylococci are generally beta-lactamase positive and considered resistant to AMP and TIC, but greater than 99% of 1,137 Staphylococcus aureus isolates and 92% of coagulase-negative staphylococcal isolates were susceptible to T/C, with comparable figures obtained for A/C and A/S. The activity of TIC against Bacteroides fragilis was improved up to 64-fold by clavulanic acid, with a definite but less pronounced effect on the non-fragilis Bacteroides species. Ninety-seven percent of strains of other anaerobic genera were susceptible to both TIC and T/C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319515 TI - Ticarcillin/clavulanate for the treatment of female genital tract infections. Efficacy, safety and comparative microbiology. AB - In an open study, ticarcillin/clavulanate was used to treat upper genital tract infections in 91 women. The clinical success rate was 92% in outpatient-acquired salpingitis (pelvic inflammatory disease), 50% in salpingitis with tuboovarian abscess, 85% in postpartum endometritis, 87% in endometritis after chorioamnionitis and 90% in postoperative parametritis. The primary adverse reaction was diarrhea, in 10 patients. Among the 129 aerobes isolated, 18 (14%) were beta-lactamase positive, as were 32% (20/63) of the anaerobes. PMID- 2319516 TI - Intravenous pulsed steroids in rheumatoid arthritis: a comparative dose study. AB - This prospective, double blind study was undertaken to test the efficacy of intravenous "minipulse" (100 mg) methylprednisolone (MP) therapy versus standard pulse (1000 mg) MP therapy in rheumatoid arthritis (RA). Thirty-six patients with RA synovitis flares were randomized to receive either 100 or 1000 mg MP IV QD x 3 doses. These 2 universally comparable groups exhibited no statistically significant differences in their striking prompt and sustained clinical improvement. These data suggest that minipulse MP is as efficacious as conventional pulse MP in the treatment of RA flares. PMID- 2319517 TI - Rifampin therapy in rheumatoid arthritis. AB - Several second-line antirheumatic agents possess both immunosuppressive and antimicrobial properties. Rifampin is an antimicrobial agent recently found to exhibit immunosuppressive activity in both animal and human studies. Intraarticular rifamycin SV, a rifampin derivative, has been reported to cause dramatic improvement in gonarthritis in 15 patients with rheumatoid arthritis (RA). These reports along with the personal observation of spontaneous improvement of arthritic symptoms in 2 patients with RA treated with rifampin at our institution, prompted us to conduct a pilot study using oral rifampin at 600 1200 mg daily in 8 patients with active, adult onset, seropositive RA. Although, no clinically important or statistically significant improvement occurred in any of the outcome variables measured (p greater than 0.12), the power of this study to detect such differences was limited. Alkaline phosphatase increased modestly in 7 patients. One patient developed an acute, drug induced, flu-like syndrome with marked elevation of liver enzymes which resolved promptly with drug withdrawal. We conclude that the potential effectiveness of oral rifampin therapy in RA is doubtful. PMID- 2319518 TI - Atlantoaxial subluxation in systemic lupus erythematosus: further evidence of tendinous alterations. AB - We prospectively determined the frequency of atlantoaxial subluxation in a group of patients with systemic lupus erythematosus (SLE) and analyzed its relationship with tendinous laxity, Jaccoud's syndrome and other features of the disease. Five of 59 patients (8.5%) had atlantoaxial subluxation. No patient presented atlantoaxial subluxation in neutral lateral cervical radiographs but all 5 had anterior atlantoaxial subluxation in full flexion films; one patient also had lateral subluxation. The 5 patients with atlantoaxial subluxation were compared with the remaining 54. Mean SLE disease duration was longer in patients with atlantoaxial subluxation (12 years) than in those without (6.6 years) (p less than 0.01). Jaccoud's syndrome, patellar tendon elongation and articular hypermobility were significantly more frequent in patients with atlantoaxial subluxation. The presence or history of arthritis failed to distinguish patients with and without atlantoaxial subluxation, while chronic renal failure and increased serum parathyroid hormone levels were significantly associated to the presence of atlantoaxial subluxation. We suggest that atlantoaxial subluxation is further evidence of tendinous alterations seen in patients with SLE. PMID- 2319519 TI - Sjogren's syndrome in systemic lupus erythematosus. AB - Sixty unselected consecutive patients with systemic lupus erythematosus (SLE) were prospectively evaluated for evidence of Sjogren's syndrome. This was diagnosed in the patients whose minor labial salivary gland biopsy was graded greater than or equal to 3 (according to Chisolm and Mason), who also had keratoconjunctivitis sicca (positive rose bengal eye test) and/or xerostomia (subjective xerostomia and decreased stimulated parotid flow rate). Lip biopsy revealed focal round cell infiltration compatible with a greater than or equal to 3 grade in 11 patients, minimal perivascular infiltration in 21 patients and no infiltration in 28. In the positive biopsy group (greater than or equal to 3 grade) subjective xerophthalmia, decreased parotid flow rate, parotid gland enlargement, lymphadenopathy, presence of rheumatoid factor and anti-La (SSB) antibodies were significantly commoner than in the others. Of the 11 patients of this group, 5 had keratoconjunctivitis sicca which sufficed for the diagnosis of Sjogren's syndrome, suggesting a prevalence of 8.3% in our population with SLE. In these individuals subjective xerophthalmia (40%), positive Schirmer's I eye test (60%), decreased parotid flow rate (80%), parotid gland enlargement (80%) and presence of rheumatoid factor (80%) and anti-La (SSB) antibodies (80%) were significantly more frequent than in the remaining patients, whereas significant differences regarding other features of SLE were not observed. Our results suggest that Sjogren's syndrome in SLE is relatively rare and usually mild. Furthermore, it may present more similarities to primary Sjogren's syndrome than to secondary Sjogren's syndrome accompanying rheumatoid arthritis. PMID- 2319520 TI - Ultrastructural pathology of skeletal muscle in systemic lupus erythematosus. AB - Muscle biopsies from 12 patients with systemic lupus erythematosus (SLE) who presented with muscle weakness and myalgias were studied ultrastructurally. Two different alterations were present, myositis (11 cases), and vacuolar myopathy (1 case). The myositis exhibited muscle atrophy, microtubular inclusions, and a mononuclear cell infiltration. In one case, with increased serum creatine phosphokinase, fiber necrosis was evident. Capillary abnormalities included thickening and reduplication of basement membrane, alterations of endothelium and microtubular inclusions. The vacuolar myopathy also showed vacuolated muscle fibers and occasional zebra bodies. The different associations between muscle diseases and SLE are grouped. Our data suggest that SLE myositis is a distinct clinical and pathological entity. The SLE vacuolar myopathy is a pathological entity clinically undistinguishable from SLE myositis. PMID- 2319521 TI - Systemic lupus erythematosus in men: a multivariate analysis of gender differences in clinical manifestations. AB - The marked gender influence on the occurrence of systemic lupus erythematosus (SLE) indicates that genetic and hormonal factors may be important in the etiology of this illness. However, few differences in clinical manifestations between males and females have been reported. To further investigate gender differences in SLE, the prevalence of 23 clinical manifestations of SLE were compared in a cohort of 62 men and 299 women. After adjusting for differences in age, race, and duration of followup, men were found to more commonly have seizures (odds ratio = 1.65; 95% confidence interval = 1.09, 2.49), and showed a trend to progress to renal failure more often (odds ratio = 1.40; 95% confidence interval = 0.96, 2.03) than women. Gender differences were not evident for the remaining 21 clinical features. The clinical similarity between men and women with SLE represents a circumstance in which the use of clinically defined patient subsets does not appear to facilitate the investigation of potential pathogenetic or etiologic factors. PMID- 2319522 TI - Genitourinary manifestations of fibrositis: an increased association with the female urethral syndrome. AB - Six of 50 female patients with fibromyalgia (fibrositis) but none of 50 rheumatic disease controls fulfilled accepted definitions for the female urethral syndrome. Genitourinary manifestations of this condition and its relationship to fibrositis are reviewed. PMID- 2319523 TI - Superior vena cava syndrome caused by systemic lupus erythematosus in a patient with longstanding rheumatoid arthritis. AB - Superior vena cava syndrome is mostly related to a malignant process, but many different benign causes have also been described. We report a patient with longstanding classic rheumatoid arthritis (RA), who developed a superior vena cava syndrome due to mediastinal lymphadenopathy. At that time she also fulfilled the ARA criteria for systemic lupus erythematosus (SLE). Histological examination of a lymph node biopsy revealed necrosis, hematoxylin bodies and LE cells, while a great amount of amorphous proteinaceous material was seen positive with immunofluorescence for IgG, IgM and complement (C3 and Clq). A diagnosis of superior vena cava syndrome due to mediastinal lymphadenopathy in a patient with SLE which had evolved from longstanding RA was established. PMID- 2319524 TI - Paragonimiasis: an infrequent but treatable cause of hemoptysis in systemic lupus erythematosus. AB - Hemoptysis in systemic lupus erythematosus (SLE) may occur in up to 17% of cases. The vast majority of the cases are secondary to bacterial, tuberculosis or opportunistic infections. Also uremia, pulmonary embolism and lung hemorrhage must be considered. The majority of the above referred entities are usually alarming events in any patient with SLE. In contrast, we describe a patient with inactive SLE, who developed hemoptysis secondary to Paragonimus sp., which was treated "easily" with praziquantel. Fluke infection must be considered in the differential diagnosis of hemoptysis in SLE. PMID- 2319526 TI - Inflammatory sacroiliitis in childhood. AB - A 27-month-old boy and a 10-month-old girl with unilateral inflammatory sacroiliitis are described. Both presented with refusal to walk or to stand. Increased erythrocyte sedimentation rate and negative HLA-B27 were found in both cases. There were no laboratory findings to suggest an underlying rheumatic disease. Radiograms of the sacroiliac (SI) joints, lumbosacral spines and the hip joints were normal. Joint/bone scan revealed increased radionuclide activity over the involved SI joints in both cases. Computerized tomograms of the SI joints were abnormal in one patient. Both patients improved with aspirin, recovered and had no sequelae. Inflammatory sacroiliitis appears to be transient and benign. It is a rare event in young children. Possibly some of them are being treated as though they had septic arthritis. PMID- 2319525 TI - Allergic granulomatosis and angiitis (Churg-Strauss syndrome) presenting as acute acalculous cholecystitis. AB - A patient with bronchial asthma and hypereosinophilia developed acute acalculous cholecystitis. Histopathologic study of the surgically removed gallbladder revealed allergic granulomatosis and angiitis (Churg-Strauss syndrome). Allergic granulomatosis and angiitis having acute acalculous cholecystitis as an initial manifestation is rare. It should be recognized that acute acalculous cholecystitis may be the initial sign of a systemic vasculitis, specifically allergic granulomatosis and angiitis. PMID- 2319527 TI - Pseudopseudarthrosis in a patient with ankylosing spondylitis. AB - There is a growing consensus that the mechanism leading to extensive discovertebral destruction (type III) in most patients with ankylosing spondylitis relates to fracture and subsequent pseudarthrosis. We introduced the term "pseudopseudarthrosis" to describe (in our case) the occurrence of abnormal motion between 2 fused spinal segments, resulting in extensive discovertebral destruction without fracture or pseudarthrosis. PMID- 2319528 TI - Hemothorax--an unusual presentation of spinal fracture in ankylosing spondylitis. AB - Patients with ankylosing spondylitis are susceptible to spinal fractures. In many cases there is no history of associated trauma or only minor trauma. The instability of such fractures and complicating neurologic sequelae are well documented. We describe an unusual complication of ankylosing spondylitis, hemothorax secondary to spinal fracture, that to our knowledge has not been previously reported. Further, we reemphasize that the instability of such fractures may lead to significant paravertebral soft tissue and vascular injuries. PMID- 2319529 TI - Coincidental autoimmune hemolytic anemia and massive pulmonary hemorrhage in systemic lupus erythematosus. PMID- 2319530 TI - Lack of association between hypothyroidism and chondrocalcinosis. PMID- 2319531 TI - Upper limb lymphedema in psoriatic arthritis. PMID- 2319532 TI - An overlapping case of ulcerative colitis and polymyositis. PMID- 2319533 TI - Trigeminal sensory neuropathy with dermatomyositis associated with a pancreatic malignancy. PMID- 2319534 TI - Antidepressant therapy and rheumatoid arthritis. PMID- 2319535 TI - Ileocaecal perforation and bleeding--are non-steroidal anti-inflammatory drugs (NSAIDs) responsible? PMID- 2319536 TI - Baclofen-induced epilepsy. PMID- 2319537 TI - Spontaneous mesenteric haematoma and small bowel infarction complicating oral anticoagulant therapy. PMID- 2319538 TI - True spontaneous rupture of the common iliac vein. PMID- 2319539 TI - Numb clumsy hands may indicate a surgically treatable cause of myelopathy in the elderly. PMID- 2319540 TI - Portal hypertension due to hydatid disease of the liver. PMID- 2319541 TI - Transsexuality. PMID- 2319542 TI - Medical student selection. PMID- 2319543 TI - Importance of early diagnosis of acute spinal extradural abscess. PMID- 2319544 TI - Honey--a remedy rediscovered. PMID- 2319545 TI - Our survival as a species. PMID- 2319546 TI - Intravenous antibiotics at home in children with cystic fibrosis. PMID- 2319547 TI - Chronic asthma and hypnotherapy. PMID- 2319548 TI - Extracorporeal shock wave lithotripsy for gallstones. PMID- 2319549 TI - Osteogenesis imperfecta and other bone disorders in the differential diagnosis of unexplained fractures. PMID- 2319550 TI - Pattern, severity and aetiology of injuries in victims of assault. AB - Although the incidence of assault and other violent crime is increasing in the UK, the cause and overall pattern of injury, and the need for admission have not been defined in adult victims who attend hospital. In a prospective study, all 539 adult victims of assault attending a major city centre Accident & Emergency department in 1986 were therefore interviewed and examined. Facial injury was extremely common: 83% of all fractures, 66% of all lacerations and 53% of all haematomas were facial. The upper limb was the next most common site of injury (14% of all injuries). Twenty-six per cent of victims sustained at least one fracture and nasal fractures were the most frequently observed skeletal injuries (27%) followed by zygomatic fractures (22%) and mandibular body (12%), angle (12%) and condyle (9%) fractures. Seventeen per cent of victims required hospital admission. Overall, the type of injury observed correlated with the alleged weapon used (P = less than 0.001) though 20% of victims who reported attacks with sharp weapons sustained only haematomas or fractures. Injury most often resulted from punching (72% of assaults) or kicking (42% of assaults). Only 6% of victims reported injury with knives but 11% were injured by broken drinking glasses. Those who were kicked were most likely to need hospital admission. PMID- 2319551 TI - Road traffic accidents before and after seatbelt legislation--study in a district general hospital. AB - Injuries among samples of car accident cases attending the Accident & Emergency (A & E) department of a District General Hospital (DGH) in the year before and after the introduction of seat belt legislation were classified applying the Abbreviated Injury Scale using information recorded in the patient case notes. Those who died or did not attend an A & E department were not included in the sampling frame. The number of those who escaped injury increased by 40% and those with mild and moderate injuries decreased by 35% after seatbelt legislation. There was a significant reduction in soft tissue injuries to the head. Only whiplash injuries to the neck showed a significant increase. PMID- 2319552 TI - Early pre-surgical treatment of the cleft palate patient. PMID- 2319553 TI - Problems of follow-up for abnormal cervical smears: discussion paper. PMID- 2319554 TI - Vicious circles in reflex sympathetic dystrophy--a hypothesis: discussion paper. PMID- 2319555 TI - Inhibitors of human leukocyte proteinase-3. PMID- 2319557 TI - Synthesis and cardiac electrophysiological activity of N-substituted-4-(1H imidazol-1-yl)benzamides--new selective class III agents. AB - The synthesis and cardiac electrophysiological activity of 18 N-substituted imidazolylbenzamides or benzene-sulfonamides are described. Compounds 6a,d,f-k and 11 exhibited potency in the in vitro Purkinje fiber assay comparable to that of N-[2-(diethylamino)ethyl]-4- [(methylsulfonyl)amino]benzamide (1, sematilide), a potent selective class III agent which is undergoing clinical trials. These data indicate that the 1H-imidazol-1-yl moiety is a viable replacement for the methylsulfonylamino group for producing class III electrophysiological activity in the N-substituted benzamide series. N-[2-(Diethylamino)ethyl]-4-(1H-imidazol-1 yl)benzamide dihydrochloride (6a) was further studied in two in vivo models of reentrant arrhythmias and showed potency and efficacy comparable to those of 1. PMID- 2319556 TI - Synthesis and pharmacological studies of N-[4-[2-hydroxy-3-[[2-[4-(1H-imidazol-1- yl)phenoxy]ethyl]amino]propoxy]phenyl]methanesulfonamide, a novel antiarrhythmic agent with class II and class III activities. PMID- 2319558 TI - Conformational analysis of cyproheptadine hydrochloride. AB - A nuclear magnetic resonance and theoretical study on the conformations and molecular flexibility of cyproheptadine hydrochloride (1) is reported. In the 1H NMR spectrum of 1 in CDCl3, two conformational forms are observed to occur in an approximate ratio of 1:4. In both forms, NOE and coupling constant measurements suggested that the terminal N-methyl group is equatorial. NOE experiments identified the more populated conformer (labeled D) as similar to the form seen in the X-ray crystal structure of cyproheptadine. The other form observed (A) may in principle be converted to D via either inversion of the central ring (T(inv)) or concerted nitrogen (N(inv)) and piperidine ring inversion (P(inv)). Chemical exchange peaks in the 400-MHz 2D NOESY/chemical-exchange spectrum suggested that the latter mechanism is responsible for interconversion between the two forms. A theoretical study of the various interconversion processes using both molecular mechanics (MM2) and molecular orbital (AM1) approaches is also reported. PMID- 2319559 TI - Novel quinuclidine-based ligands for the muscarinic cholinergic receptor. AB - Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile. PMID- 2319561 TI - Selective class III antiarrhythmic agents. 1 Bis(arylalkyl)amines. AB - A series of bis(arylalkyl)amines is described and their effects on prolonging effective refractory period in isolated cardiac tissue listed. Most compounds prolonged the cardiac action potential without significantly altering the maximum rate of depolarization and may be defined as selective class III antiarrhythmic agents. It was found that a particularly advantageous structural feature was to have a methanesulfonamido moiety on both of the aryl rings. Thus, compound 16 [1 (4-methanesulfonamidophenoxy)2-[N-(4-methanesulfonamidophene thyl)-N- methylamine]ethane] was selected for further investigations. The compound is highly potent and selective class III agent which acts by blockade of cardiac potassium channels. PMID- 2319560 TI - Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma. AB - A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant improvement in the 1 h post-head-injury neurological status (grip test score) by as much as 168.6% of the control has been observed. The most efficacious compound in this assay (30) showed an increase in the 1-week survival of 78.6% as compared to 27.3% for the vehicle-treated mice in the head-injury model. Based on its biological profile, 21-[4-(2,6-di-1-pyrrolidinyl-4 pyrimidinyl)-1-piperazinyl]-16 alpha- methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (30) was selected for further evaluation and is currently entering phase I clinical trials for the treatment of head and spinal trauma. PMID- 2319562 TI - Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes. AB - The synthesis of novel 1-thio-substituted butadienes, designed as mechanism-based 5-lipoxygenase inhibitors, is described. The structure of these compounds closely resembles a proposed high-energy intermediate during the lipoxygenation of arachidonic acid. They demonstrate 5-lipoxygenase inhibition in vitro and in vivo. The most potent compound is 15a with an IC50 of 1.8 microM in vitro. LTC4 release was inhibited by 80% after intraperitoneal administration of 15c at a dose of 2 mg/kg. PMID- 2319563 TI - DNA-directed alkylating agents. 1. Structure-activity relationships for acridine linked aniline mustards: consequences of varying the reactivity of the mustard. AB - A series of DNA-targeted aniline mustards have been prepared, and their chemical reactivity and in vitro and in vivo cytotoxicity have been evaluated and compared with that of the corresponding simple aniline mustards. The alkylating groups were anchored to the DNA-intercalating 9-aminoacridine chromophore by an alkyl chain of fixed length attached at the mustard 4-position through a link group X, while the corresponding simple mustards possessed an electronically identical small group at this position. The link group was varied to provide a series of compounds of similar geometry but widely differing mustard reactivity. Variation in biological activity should then largely be a consequence of this varying reactivity. Rates of mustard hydrolysis in the two series related only to the electronic properties of the link group, with attachment of the intercalating chromophore having no effect. The cytotoxicities of the simple mustards correlated well with group electronic properties (with a 200-300-fold range in IC50S). The corresponding DNA-targeted mustards were much more potent (up to 100 fold), but their IC50 values varied much less with linker group electronic properties. Most of the DNA-targeted mustards showed in vivo antitumor activity, being both more active and more dose-potent than either the corresponding untargeted mustards and chlorambucil. These results show that targeting alkylating agents to DNA by attachment to DNA-affinic units may be a useful strategy. PMID- 2319564 TI - Synthesis and antitumor evaluation in mice of certain 7-deazapurine (pyrrolo[2,3 d]pyrimidine) and 3-deazapurine (imidazo[4,5-c]pyridine) nucleosides structurally related to sulfenosine, sulfinosine, and sulfonosine. AB - 7-Deaza (pyrrolo[2,3-d]pyrimidine) and 3-deaza (imidazo[4,5-c]pyridine) congeners of sulfenosine (5a and 9), sulfinosine (6a and 10), and sulfonosine (7a) have been prepared and evaluated for their antileukemic activity in mice. Amination of 2-amino-7-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidine-4(3H)-th ion e (4a) and its 2'-deoxy analogue (4c) with a chloramine solution gave the corresponding 4 sulfenamides (5a and 5c, respectively), which on selective oxidation with m chloroperoxybenzoic acid (MCPBA) gave the respective diastereomeric 2-amino-7 beta-D-ribofuranosyl-pyrrolo[2,3-d]pyrimidine-4-sulfinamide (7-deazasulfinosine, 6a) and its 2'-deoxy derivative (6c). A similar amination of 7-(2-deoxy-beta-D erythro-pentofuranosyl)pyrrolo[2,3-d]pyrimidine-4(3H)- thione (4b) gave the corresponding 4-sulfenamide derivative (5b). Oxidation of 5b with 1 molar equiv of MCPBA furnished (R,S)-7-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrrolo[2,3 d]pyrimidine- 4- sulfinamide (6b), whereas use of excess of MCPBA afforded the corresponding sulfonamide derivative (7b). Treatment of 3-deaza-6-thioguanosine (8) with a chloramine solution gave 3-deazasulfenosine (6-amino-1-beta-D- ribofuranosylimidazo[4,5-c]pyridine-4-sulfenamide, 9). Controlled oxidation of 9 with MCPBA afforded 3-deazasulfinosine (10). As gauged by increases in the mean postinoculation life spans of L1210 inoculated mice, none of these nucleosides exhibited biologically significant activity (T/C greater than or equal to 125). Even so, antileukemic activity appeared to be influenced, albeit not uniformly, by structural modifications in the base and carbohydrate moieties of sulfenosine and sulfinosine. Thus, while several of the compounds were lacking in cytotoxic activity, eight others (4c, 5a, 5c, 6a, 6b, 7b, 9, and 10) were estimated to have reduced body burdens of viable L1210 cells by 16-77%. PMID- 2319565 TI - Intrinsic isotope effects suggest that the reaction coordinate symmetry for the cytochrome P-450 catalyzed hydroxylation of octane is isozyme independent. AB - The mechanism of the omega-hydroxylation of octane by three catalytically distinct, purified forms of cytochrome P-450, namely, P-450b, P-450c, and P 450LM2, was investigated by using deuterium isotope effects. The deuterium isotope effects associated with the omega-hydroxylation of octane-1,1,1-2H3, octane-1,8-2H2, and octane-1,1,8,8-2H4 by all three isozymes were determined. From these data the intrinsic isotope effects were calculated and separated into their primary and secondary components. The primary intrinsic isotope effect for the reaction ranged from 7.69 to 9.18 while the secondary intrinsic isotope effect ranged from 1.13 to 1.25. Neither the primary nor secondary isotope effect values were statistically different for any of the isozymes investigated. These data are consistent with a symmetrical transition state for a mechanism involving initial hydrogen atom abstraction followed by hydroxyl radical recombination which is essentially independent of the specific isozyme catalyzing the reaction. It is concluded that (1) in general the porphyrin-[FeO]3+ complex behaves as a source of a triplet-like oxygen atom, (2) the regioselectivity for the site of oxidation is dictated by the apoprotein of the specific isozyme of cytochrome P 450 catalyzing the reaction, and (3) the maximum primary intrinsic isotope effect for any cytochrome P-450 catalyzed oxidation of a carbon center is about 9, assuming no tunneling effects. PMID- 2319566 TI - The synthesis and antibacterial activities of quinolones containing five- and six membered heterocyclic substituents at the 7-position. AB - A series of 6-fluoro-7-substituted-1-ethyl-1,4-dihydro-4-oxoquinoline-3 carboxylic acids were prepared. The substituents at the 7-position included five- and six-membered heterocyclic rings such as oxazoline and oxazine as well as five membered heteroaromatic rings such as oxazoles and imidazoles. The structure- activity relationships (SAR) of these compounds indicated that oxazole substituents containing a 2-methyl group had the greatest in vitro potency. The compounds showed greater in vitro antibacterial activity against Gram-positive organisms than against Gram-negative organisms. PMID- 2319567 TI - Analogues of 1,5-bis(4-amidinophenoxy)pentane (pentamidine) in the treatment of experimental Pneumocystis carinii pneumonia. AB - A series of 33 analogues of the anti-Pneumocystis carinii drug 1,5-bis(4 amidinophenoxy)pentane (pentamidine) was synthesized for screening against a rat model of P. carinii pneumonia (PCP). Twenty-five of the compounds showed efficacy against PCP when compared to a saline-treated control group. Two compounds, 1,4 bis(4-amidinophenoxy)butane (butamidine, 6) and 1,3-bis(4-amidino-2 methoxyphenoxy)propane (DAMP, 16), were statistically more effective than the parent drug in treating PCP in the rat model of infection. In addition to their activity against PCP, the compounds were also evaluated for antitrypsin activity, ability to inhibit thymidylate synthetase, affinity for DNA, and toxicity. No correlation was observed between the tested molecular interactions of the diamidines and their effectiveness against PCP. PMID- 2319568 TI - Diels-Alder adducts of vinyl porphyrins: synthesis and in vivo photodynamic effect against a rat bladder tumor. AB - Benzoporphyrin derivatives have been proposed as potential photosensitizers for photodynamic therapy. We have prepared a number of benzoporphyrin derivatives and tested their effect, in combination with red light, on the N-[4-(5-nitro-2-furyl) 2-thiazolyl]formamide (FANFT) induced rat bladder tumor (AY-27) transplanted into Fischer CDF(F344)/CrlBr rats. Tetracyanoethylene (TCNE) adducts showed very little activity, which may be attributable to their poor tumor uptake or to chemical instability of the adduct under physiological conditions. However, dimethyl acetylenedicarboxylate (DMAD) adducts tested showed greater cytotoxic effect than hematoporphyrin derivative and similar activities to metallopurpurins when tested under the same protocol. PMID- 2319569 TI - Synthesis of perfluoroalkylated xylitol ethers and esters: new surfactants for biomedical uses. AB - New, well-defined surfactants and cosurfactants were synthesized with the objective of enhancing the stability of fluorocarbon emulsions destined to serve as oxygen carriers for biomedical applications. Monoperfluoroalkylated ethers of xylitol were achieved by addition of perfluoroalkyl iodide on the double bond of a protected xylitol allyl ether in a one-step addition-elimination reaction. Monoesters were obtained specifically on position 5 by treating 1,2:3,4-di-O isopropylidenexylitol with perfluoroalkylated acid chlorides of various chain lengths in pyridine at room temperature. The products display strong surface activity and produce a remarkable synergistic stabilization of a fluorocarbon/Pluronic F-68 type emulsion. Biocompatibility data are reported, which include in vitro toxicity tests on Namalva cell cultures and hemolysis tests on human blood cells; the latter was found to decrease as the length of the F-alkyl chain increased. IV injection in mice (n = 10) showed that these products were innocuous at 400-1000 mg/kg of body weight. Preliminary exchange-perfusion experiments on rats with an emulsion containing the F-octyl xylitol ether were encouraging. PMID- 2319571 TI - Death. PMID- 2319570 TI - Moral intuition, good deaths and ordinary medical practitioners. AB - Debate continues over the acts/omissions doctrine, and over the concepts of duty and charity. Such issues inform the debate over the moral permissibility of euthanasia. Recent papers have emphasised moral sensitivity, medical intuitions, and sub-standard palliative care as some of the factors which should persuade us to regard euthanasia as morally unacceptable. I argue that these lines of argument are conceptually misdirected and have no bearing on the bare permissibility of voluntary euthanasia. Further, some of the familiar slippery slope arguments against voluntary euthanasia compromise the principle of autonomy to which both supporters and opponents of euthanasia adhere. I discuss a model for doctor/patient relationships which can be applied to cases which would be seen by all disputants as strong prima facie cases for euthanasia. I argue that in certain cases it will be ordinary medical practitioners who are duty-bound to assist death. PMID- 2319572 TI - Screening for genetic disorders: therapeutic abortion and IVF. AB - This paper examines a proposal to make use of IVF techniques to provide an alternative to therapeutic abortion of fetuses with genetic abnormalities. We begin by describing the proposed procedure, and then show that, considered in itself, it is morally on a par with therapeutic abortion. However, once the wider practical implications are brought into view, the proposed new procedure loses its initial appeal. The pros and cons are not sufficiently clear-cut entirely to rule out the IVF procedure, so the paper concludes by indicating some further complications which may follow, should the procedure come to be adopted. PMID- 2319573 TI - Danish ethics council rejects brain death as the criterion of death. AB - In Denmark, which alone in Western Europe has not accepted brain death as the criterion of death, the newly established Danish Council of Ethics has issued a report suggesting that in Denmark the criterion of death should still be the cessation of cardiac activity. The council bases its conclusion on the concept of death in everyday experience and its ethical implications. PMID- 2319574 TI - Morality of surgical abortion at twenty weeks. PMID- 2319575 TI - Ethical obligation arising from routine screening. PMID- 2319576 TI - What doctors should call their patients. PMID- 2319577 TI - Three cases of partial trisomy 7q owing to rare structural rearrangements of chromosome 7. AB - Three cases of partial trisomy 7q are described. One case had duplication of region 7q22.1----q31.2 owing to a de novo direct intra-arm intrachromosomal duplication. The other two cases, first cousins, were trisomic for 7q34----qter, resulting from recombination within the inserted segment of a dir ins(7;17)(q34;q23.1q25.3)mat. All three cases had a number of the already recorded manifestations of partial trisomy 7q, namely strabismus, low set ears, depressed nasal bridge, small nose, hypotonia, and mental retardation. PMID- 2319578 TI - Yunis-Varon syndrome with severe osteodysplasty. AB - We report two male sibs and two female sibs from separate families, both with normal parents, who had a lethal condition with features of the Yunis-Varon syndrome and radiological signs of severe osteodysplasty. Autosomal recessive inheritance is likely in both families. The additional features described represent further delineation of the phenotype of the Yunis-Varon syndrome. PMID- 2319579 TI - Moebius syndrome. PMID- 2319580 TI - A familial syndrome of microcephaly, sparse hair, mental retardation, and seizures. AB - A family is described in which the father and three of his seven children have microcephaly, mild to moderate mental retardation, and sparse hair. The two affected boys have generalised seizures in addition. PMID- 2319581 TI - Neuroblastoma in a patient with Sotos' syndrome. AB - Sotos' syndrome, or cerebral gigantism, is a disorder of growth regulation. Tumours have occasionally been reported in children with Sotos' syndrome, but it is uncertain whether this is a coincidence, or whether it is aetiologically related to the underlying disorder of growth. We report a 15 month old child with a paraspinal neuroblastoma and Sotos' syndrome and suggest that children with this condition may be at higher risk for developing tumours than the general population. PMID- 2319583 TI - Inverted tandem duplication of 8p12----p23.1 in a child with increased activity of glutathione reductase. AB - At least 16 cases of inversion tandem duplications of the short arm of chromosome 8 have been reported. Structural rearrangements of chromosome 8 have made it possible to localise the gene for glutathione reductase (GSR) to 8p21.1. We report here on a 16 month old boy with mental retardation with partial trisomy 8 owing to a de novo inv dup(8)(p12----p23.1). PMID- 2319584 TI - An apparent de novo terminal deletion of chromosome 2 (pter----p24:). PMID- 2319582 TI - Compound heterozygosity for abetalipoproteinaemia and familial hypobetalipoproteinaemia. AB - A 10 year old boy with abetalipoproteinaemia is reported. His mother and grandfather suffered from familial hypobetalipoproteinaemia, but his father had a normal lipoprotein profile. This is the first report of abetalipoproteinaemia resulting from compound heterozygosity for abetalipoproteinaemia and familial hypobetalipoproteinaemia. PMID- 2319585 TI - A workshop on Marfan syndrome, 10 June 1989, Farmington, CT, USA. PMID- 2319587 TI - Unilateral disomy as a possible explanation for Russell-Silver syndrome. PMID- 2319586 TI - Angelman's syndrome, abnormality of 15q11-13, and imprinting. PMID- 2319588 TI - An exclusion map of Marfan syndrome. AB - The combined genetic data between the Marfan syndrome and 75 informative loci on 18 autosomes were used to construct an exclusion map for this disorder. Data are also presented for a further two unmapped markers. The most likely location of the Marfan syndrome gene is highlighted and all the unexcluded areas of the genome are displayed in a graphical form. This exclusion map shows that almost 75% of the genome has been excluded as a likely location for the Marfan syndrome gene in the majority of the families studied. Apart from chromosomes 8, 13, 21, and 22, for which no data were available, other regions not excluded yet include 5p, 6p, 9p, 10p, 12p, 15, 17p, 18, and 20p. Future linkage analysis using markers located in the highlighted regions should facilitate the identification of the site of the Marfan syndrome gene. PMID- 2319589 TI - Exclusion of COL2A1 as a candidate gene in a family with Wagner-Stickler syndrome. AB - A large family with Wagner's vitreoretinal degeneration but none of the non ocular features of Stickler's syndrome has been studied with gene probes for type II collagen. Recombination has been observed, thus excluding type II collagen as the site of mutation in this family. This report supports other published evidence that the Wagner-Stickler syndrome is genetically heterogeneous. PMID- 2319591 TI - Potassium channel in rabbit corneal endothelium activated by external anions. AB - The apical membrane of the rabbit corneal endothelium contains a potassium selective ionic channel. In patch-clamp recordings, the probability of finding the channel in the open state (Po) depends on the presence of either HCO3- or Cl- in the bathing medium. In a methane sulfonate-containing bath, Po is less than 0.05 at all physiologically relevant transmembrane voltages. With 0 mM [HCO3-]o at +60 mV, Po was 0.085 and increased to 0.40 when [HCO3-]o was 15 mM. With 4 mM [Cl-]o at +60 mV, Po was 0.083 and with 150 mM Cl-, Po increased to 0.36. Low Po's are also found when propionate, sulphate, bromide, and nitrate are the primary bath anions. The mechanism of action of the anion-stimulated K+ channel gating is not yet known, but a direct action of pH seems unlikely. The alkalinization of cytoplasm associated with the addition of 10 mM (NH4)2SO4 to the bath and the acidification accompanying its removal do not result in channel activation nor does the use of Nigericin to equilibrate intracellular pH with that of the bath over the pH range of 6.8 to 7.8. Channel gating also is not affected by bathing the internal surface of the patch with cAMP, cGMP, GTP-gamma s, Mg2+ or ATP. Blockers of Na/H+ exchange, Na(+)-HCO3- cotransport, Na(+)-K+ ATPase and carbonic anhydrase do not block the HCO3- stimulation of Po. Several of the properties of the channel could explain some of the previously reported voltage changes that occur in corneal endothelial cells stimulated by extracellular anions. PMID- 2319590 TI - Electrically silent anion transport through bilayer lipid membrane induced by tributyltin and triethyllead. AB - The method of the measurement of the nonelectrogenic fluxes of hydrogen (or hydroxyl) ions (JH) based on the local proton gradients formation in the unstirred layers near a bilayer lipid membrane (BLM) is applied for recording the nonelectrogenic anion/OH- exchange on BLM induced by tributyltin (TBT) and a novel carrier (Hager, A., Moser, I., & Berthold, W. 1987. Z. Naturforsch., 42C:1116-1120), triethyllead (TEL). This method has been used previously for measuring the cation fluxes through BLM. TBT and TEL are shown to be equally efficient in the induction of Cl-/OH- exchange. JH induced by TBT is constant at 4 less than pH less than 7. JH decreases at pH less than 4 and pH greater than 7. Both ionophores have a transport sequence: I- greater than Br- greater than Cl- greater than F-. The quantitative measurements reveal that TEL better discriminates these four anions than TBT. It is concluded that this method may prove helpful in a search and study of anion/OH(-)-exchangers isolated from natural membranes. PMID- 2319592 TI - Effect of deletions at structural domains of group II intron bI1 on self-splicing in vitro. AB - Some group II introns can undergo a protein-independent splicing reaction with the basic reaction pathway similar to nuclear pre-mRNA splicing and the catalytic functions of some of the structural components have been determined. To identify further functional domains, we have generated an ensemble of partial and complete deletions of domains I, II, III and IV of the self-splicing group II intron bI1 from yeast mitochondria and studied their effects on the splicing reaction in vitro. Our results indicate that domains II and IV, which vary considerably in length and structure among group II introns, do not play a direct role in catalysis but mainly help to ensure the proper interaction between upstream and downstream catalytically active structural elements. Deletions of sub-domains of domain I and domain III indicate that these elements are involved in 5' cleavage by hydrolysis and in a reaction in trans (exon reopening), and that this function can be inhibited without affecting the normal 5' cleavage by transesterification. Yet, we infer that the helical structures affected by the mutational alterations might not contribute to this reaction mode per se but that changes within local secondary structures perturb the internal conformation of the ribozyme. Furthermore, we have designed an abbreviated version of intron bI1, with a length of 542 nucleotides, which is still catalytically active. PMID- 2319594 TI - Dissection of functional domains in phage fd adsorption protein. Discrimination between attachment and penetration sites. AB - We constructed a set of deletion mutants in the attachment protein of phage fd. These mutants lack sequences coding for sections in the amino-terminal half. All the mutants that comprise a leader sequence are incorporated into phage particles. Our data strongly suggest a bipartite organization of the amino terminal domain with (1) a region for receptor recognition and (2) a region that is necessary for penetration of the DNA into the host cell. These regions were mapped. Some evidence suggesting different roles for gene 3 protein in penetration of the outer and inner membrane are discussed. We demonstrate that the phenotypes caused by gene 3 protein in host cells can be subdivided into two groups with different sequence requirements: (1) phenotypes related to outer membrane disturbance; and (2) phenotypes related to the tolQRA transport system. PMID- 2319593 TI - Rubredoxin reductase of Pseudomonas oleovorans. Structural relationship to other flavoprotein oxidoreductases based on one NAD and two FAD fingerprints. AB - The oxidation of alkanes to alkanols by Pseudomonas oleovorans involves a three component enzyme system: alkane hydroxylase, rubredoxin and rubredoxin reductase. Alkane hydroxylase and rubredoxin are encoded by the alkBFGHJKL operon, while previous studies indicated that rubredoxin reductase is most likely encoded on the second alk cluster: the alkST operon. In this study we show that alkT encodes the 41 x 10(3) Mr rubredoxin reductase, on the basis of a comparison of the expected amino acid composition of AlkT and the previously established amino acid composition of the purified rubredoxin reductase. The alkT sequence revealed significant similarities between AlkT and several NAD(P)H and FAD-containing reductases and dehydrogenases. All of these enzymes contain two ADP binding sites, which can be recognized by a common beta alpha beta-fold or fingerprint, derived from known structures of cofactor binding enzymes. By means of this amino acid fingerprint we were able to determine that one ADP binding site in rubredoxin reductase (AlkT) is located at the N terminus and is involved in FAD binding, while the second site is located in the middle of the sequence and is involved in the binding of NAD or NADP. In addition, we derived from the sequences of FAD binding reductases a second amino acid fingerprint for FAD binding, and we used this fingerprint to identify a third amino acid sequence in AlkT near the carboxy terminus for binding of the flavin moiety of FAD. On the basis of the known architecture and relative spatial orientations of the NAD and FAD binding sites in related dehydrogenases, a model for part of the tertiary structure of AlkT was developed. PMID- 2319595 TI - Use of techniques derived from graph theory to compare secondary structure motifs in proteins. AB - A substructure matching algorithm is described that can be used for the automatic identification of secondary structural motifs in three-dimensional protein structures from the Protein Data Bank. The proteins and motifs are stored for searching as labelled graphs, with the nodes of a graph corresponding to linear representations of helices and strands and the edges to the inter-line angles and distances. A modification of Ullman's subgraph isomorphism algorithm is described that can be used to search these graph representations. Tests with patterns from the protein structure literature demonstrate both the efficiency and the effectiveness of the search procedure, which has been implemented in FORTRAN 77 on a MicroVAX-II system, coupled to the molecular fitting program FRODO on an Evans and Sutherland PS300 graphics system. PMID- 2319596 TI - Role of two proline-containing turns in the folding of porcine ribonuclease. AB - Unfolded ribonuclease (RNase) from porcine pancreas consists of a mixture of fast and slow-refolding species. The equilibrium distribution of these species differs strongly from other homologous RNases, because an additional proline residue is present at position 115 of the porcine protein. The major slow-folding species of porcine RNase contains incorrect proline isomers at Pro93 and at Pro114-Pro115. Both positions are presumably part of beta-turn structures in the native protein, as deduced from the structure of the homologous bovine RNase A. The folding kinetics of these molecules depend strongly on the conditions used. Under unfavorable conditions (near the unfolding transition), refolding is virtually blocked by the presence of the incorrect proline peptide bonds and partially folded intermediates with incorrect isomers could not be detected. As a consequence, folding is very slow under such conditions and the re-isomerization of Pro114-Pro115 is the first and rate-limiting step of folding. Under strongly native conditions (such as in the presence of ammonium sulfate), refolding is much faster. A largely folded intermediate accumulates with the turns around Pro93 and Pro114-Pro115 still in the non-native conformation. These results suggest that incorrect proline isomers strongly influence protein folding and that, under favorable conditions, the polypeptide chain can fold with two beta turns locked into a non-native conformation. We conclude, therefore, that early formation of correct turn structure is not necessarily required for protein folding. However, the presence of incorrect turns, locked-in by non-native proline isomers, strongly decreases the rate of refolding. Alternative pathways of folding exist. The choice of pathway depends on the number and distribution of incorrect proline isomers and on the folding conditions. PMID- 2319597 TI - Mechanism for aldose-ketose interconversion by D-xylose isomerase involving ring opening followed by a 1,2-hydride shift. AB - The active site and mechanism of D-xylose isomerase have been probed by determination of the crystal structures of the enzyme bound to various substrates, inhibitors and cations. Ring-opening is an obligatory first step of the reaction and is believed to be the rate-determining step for the aldose to ketose conversion. The structure of a complex with a cyclic thio-glucose has been determined and it is concluded that this is an analogue of the Michaelis complex. At -10 degrees C substrates in crystals are observed in the extended chain form. The absence of an appropriately situated base for either the cyclic or extended chain forms from the substrate binding site indicates that the isomerisation does not take place by an enediol or enediolate mechanism. Binding of a trivalent cation places an additional charge at the active site, producing a substrate complex that is analogous to a possible transition state. Of the two binding sites for divalent cations, [1] is permanently occupied under catalytic conditions and is co-ordinated to four carboxylate groups. In the absence of substrate it is exposed to solvent, and in the Michaelis complex analogue, site [1] is octahedrally coordinated, with ligands to O-3 and O-4 of the thiopyranose. In the complex with an open-chain substrate it remains octahedrally co-ordinated, with ligands to O-2 and O-4. Binding at a second cation site [2] is also necessary for catalysis and this site is believed to bind Co2+ more strongly than site [1]. This site is octahedrally co-ordinated to three carboxylate groups (bidentate co-ordination to one of them), an imidazole and a solvent molecule. It is proposed that during the hydride shift the C-O-1 and C-O-2 bonds of the substrate are polarized by the close approach of the site [2] cation. In the transition-state analogue this cation is observed at a site [2'], 1.0 A from site [2] and about 2.7 A from O-1 and O-2 of the substrate. It is likely that co ordination of the cation to O-1 and O-2 would be concomitant with ionisation of the sugar hydroxyl group. The polarisation of C-O-1 and C-O-2 is assisted by the co-ordination of O-2 to cation [1] and O-1 to a lysine side-chain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2319599 TI - Energetics of B-Z junction formation in a sixteen base-pair duplex DNA. AB - We report analysis of the NaCl-induced B-Z transition in a 16 base-pair duplex DNA with sequence designed such that when NaCl is increased the left half of the molecule undergoes the B-Z transition while the right half remains in the B-form. An equilibrium thermodynamic model based on the body of available published experimental data and the recent theoretical work of Soumpasis, which indicate, in the salt range above approximately 0.9 M-NaCl, the transition free-energy of B Z conversion in DNA is a linear function of the NaCl concentration, is employed. Analysis of the B-Z transition of the junction-containing molecule indicates the B-Z junction formed in this 16 base-pair DNA is composed of approximately three base-pairs and has a free energy of formation of approximately 4.7 kcal/mol junction. These values for the junction are in excellent agreement with published estimates of B-Z junction size and energy derived from much longer DNA pieces. PMID- 2319598 TI - Sequence and structure correlation of human ribosomal transcribed spacers. AB - We report the sequences of the transcribed spacers of human rRNA that now allow us to piece together the entire primary transcript sequence of approximately 13.3 x 10(3) base-pairs. Comparison of transcribed spacer sequences with those of variable regions of rRNA and with those of the non-transcribed spacers supports the hypothesis that the variable regions are descended from transcribed spacers. Nucleotide sequence-derived secondary structures for the 5' external transcribed spacer and for internal transcribed spacers 1 and 2 match both the sizes and shapes of the structures that were visualized 15 years ago on electron micrographs. Parts of these structures are conserved in mammals and may be related to transcript processing. PMID- 2319600 TI - Protruding domain of tomato bushy stunt virus coat protein is a hitherto unrecognized class of jellyroll conformation. AB - The capsid protein of tomato bushy stunt virus (TBSV) has two antiparallel beta sheet domains with the so-called jellyroll conformation. Contrary to previous analyses, we note that these domains are non-superimposable topologies. The TBSV shell (S) domain topology is common to many other proteins but the protruding (P) domain is a unique conformation so far found in no other protein. The TBSV capsid P domain did not arise from the S domain by a gene duplication event as previously assumed. It is proposed instead that the P domain was acquired from an as yet unidentified cellular protein. The four possible unique jellyroll topologies that might occur in proteins are discussed and illustrated. PMID- 2319601 TI - Characterization of the DNA binding activity of stable RecA-DNA complexes. Interaction between the two DNA binding sites within RecA helical filaments. AB - The DNA-binding, annealing and recombinational activities of purified RecA-DNA complexes stabilized by ATP gamma S (a slowly hydrolysable analog of ATP) are described. Electrophoretic analysis, DNase protection experiments and observations by electron microscopy suggest that saturated RecA complexes formed with single- or double-stranded DNA are able to accommodate an additional single strand of DNA with a stoichiometry of about one nucleotide of added single stranded DNA per nucleotide or base-pair, respectively, of DNA resident in the complex. This strand uptake is independent of complementarity or homology between the added and resident DNA molecules. In the complex, the incoming and resident single-stranded DNA molecules are in close proximity as the two strands can anneal in case of their complementarity. Stable RecA complexes formed with single stranded DNA bind double-stranded DNA efficiently when the added DNA is homologous to the complexed strand and then initiate a strand exchange reaction between the partner DNA molecules. Electron microscopy of the RecA-single stranded DNA complexes associated with homologous double-stranded DNA suggests that a portion of duplex DNA is taken into the complex and placed in register with the resident single strand. Our experiments indicate that both DNA binding sites within RecA helical filaments can be occupied by either single- or double stranded DNA. Presumably, the same first DNA binding site is used by RecA during its polymerization on single- or double-stranded DNA and the second DNA binding site becomes available for subsequent interaction of the protein-saturated complexes with naked DNA. The way by which additional DNA is taken into RecA-DNA complexes shows co-operative character and this helps to explain how topological problems are avoided during RecA-mediated homologous recombination. PMID- 2319602 TI - DNA sequence analysis of the mitochondrial ND4L-ND5 gene complex from Podospora anserina. Duplication of the ND4L gene within its intron. AB - A 15 kb region of the 100 kb mitochondrial genome of Podospora anserina has been mapped and sequenced (1 kb = 10(3) base-pairs). The genes for ND4L and ND5 are identified as contiguous genes with overlapping termination and initiation codons. In race A (101 kb) the gene for ND4L (4.3 kb) has a gene duplication within an intron including a second subgroup IC intron. Race s (95 kb) lacks this second gene complex. Each intron has the identical 5' exon boundary. Secondary structure analysis showed that the closest relative of the second intron is the first intron itself. The open reading frames of the two introns are also closely related to each other as well as to their counterpart in the ND4L gene of Neurospora crassa. The 9.9 kb ND5 gene starts immediately at the termination codon of ND4L and is split by two group IB introns, one group IC intron and one group II intron. The group II intron is closely related to other group II introns although its open reading frame sequence similarity with retroviral reverse transcriptase appears to be more divergent. The similarities in secondary structure and open reading frames for these six introns are discussed. PMID- 2319604 TI - Application of the method of phage T4 DNA ligase-catalyzed ring-closure to the study of DNA structure. II. NaCl-dependence of DNA flexibility and helical repeat. AB - In this work, we demonstrate that it is possible to determine the molar cyclization factor jM from single ligation reactions in which both circular and linear dimer DNA species are formed concurrently from linear monomers. This approach represents a significant improvement over previous methods, in which jM is evaluated from the ratio of the rate constants for two separate processes; namely (1) the cyclization of linear DNA and (2) the association of two linear molecules to form linear dimers. Determination of jM for a 366 base-pair molecule yields 5.8 X 10(-8) M, in close agreement with the value of 5.6 X 10(-8) M determined by Shore et al. for the same molecule. Using the current approach for the determination of jM, we have investigated the dependence on NaCl concentration (0 to 162 mM-NaCl, 1 mM-MgCl2) of both the lateral and torsional flexibilities of DNA. The principal observation is that both quantities are essentially constant over the above range of NaCl concentrations, with the persistence length P approximately 450 (+/- 15) A, and the torsional elastic constant C approximately 2.0 (+/- 0.2) X 10(-19) erg cm. These observations are in accord with the previous theoretical prediction that P becomes essentially independent of NaCl concentration above 10 to 20 mM. We have examined the dependence of the helical repeat of DNA on NaCl concentration over the above range, and have found the value of 10.44 base-pairs per turn to be essentially constant over that range. This last result suggests that earlier studies have overestimated the dependence of DNA helical twist on salt concentration. PMID- 2319603 TI - Application of the method of phage T4 DNA ligase-catalyzed ring-closure to the study of DNA structure. I. Computational analysis. AB - The tendency for relatively short (less than 500 base-pair) DNA molecules to circularize in the presence of DNA ligase is a sensitive function of both the lateral and torsional flexibilities of the molecules being studied. This tendency is reflected in a quantity known as the j-factor, which is determined experimentally by measuring the relative rates of circle and linear dimer formation at a specified concentration of linear monomer. Shimada & Yamakawa have provided an analytical representation of j that takes account of DNA molecules whose ends are not torsionally aligned. Their approach, however, assumes that contributions from helix writhe are small. Using a Monte Carlo approach for the determination of j, thereby avoiding any assumptions regarding writhe, we demonstrate that the computed, torsion angle-averaged quantity, [j], is exactly reproduced by the corresponding Shimada & Yamakawa quantity for all lengths examined. However, for DNA molecules having lengths that are substantially greater than the persistence length, P, the analysis of experimental ring-closure data using j (Shimada & Yamakawa) may lead to underestimates for the torsional elastic constant C. We demonstrate that no single set of values for P, C and the helical repeat (hR) can produce a reasonable fit of the computed j curve to the experimental values of Shore et al. This observation suggests that P, C and/or hR vary within the set of DNA molecules studied by those authors. The current computational analysis considers the effects on j of single or multiple bends in the helix axis. For single, centrally located bends, the shift in the distribution of end-to-end separations to smaller values is nearly offset by the less favorable polar alignment of the ends of the chain; the net effect being a modest change in j that is not a monotonic function of the bend angle. In contrast, polar alignment, and hence j, can be enhanced dramatically for molecules containing multiple, phased bends. However, for studies of the distribution of circle sizes formed from ligation of bend-containing DNA oligomers, the DNA lengths giving rise to maximal j values are smaller than predicted on the basis of the number of bends and the per-bend angle. This last result suggests that such studies may yield apparent bend angles that are too large. PMID- 2319606 TI - Experts agree to disagree on adjuvant therapy for breast cancer. PMID- 2319605 TI - Flexible protein sequence patterns. A sensitive method to detect weak structural similarities. AB - The concept of a flexible protein sequence pattern is defined. In contrast to conventional pattern matching, template or sequence alignment methods, flexible patterns allow residue patterns typical of a complete protein fold to be developed in terms of residue positions (elements), separated by gaps of defined range. An efficient dynamic programming algorithm is presented to enable the best alignment(s) of a pattern with a sequence to be identified. The flexible pattern method is evaluated in detail by reference to the globin protein family, and by comparison to alignment techniques that exploit single sequence, multiple sequence and secondary structural information. A flexible pattern derived from seven globins aligned on structural criteria successfully discriminates all 345 globins from non-globins in the Protein Identification Resource database. Furthermore, a pattern that uses helical regions from just human alpha haemoglobin identified 337 globins compared to 318 for the best non-pattern global alignment method. Patterns derived from successively fewer, yet more highly conserved positions in a structural alignment of seven globins show that as few as 38 residue positions (25 buried hydrophobic, 4 exposed and 9 others) may be used to uniquely identify the globin fold. The study suggests that flexible patterns gain discriminating power both by discarding regions known to vary within the protein family, and by defining gaps within specific ranges. Flexible patterns therefore provide a convenient and powerful bridge between regular expression pattern matching techniques and more conventional local and global sequence comparison algorithms. PMID- 2319607 TI - Critics air grievances about OTA report on unconventional treatments. PMID- 2319608 TI - Space radiation and cancer--danger at the final frontier? PMID- 2319609 TI - Cancer pain: its management emerges as public health issue. PMID- 2319610 TI - Improved therapeutic index of cisplatin by procaine hydrochloride. AB - The local anesthetic procaine hydrochloride (P.HCl) had little effect on the sensitivity of P388 leukemic cells to cisplatin (DDP) in vitro, but the simultaneous administration of DDP and P.HCl (40 mg/kg) to BDF1 mice produced 50% lethal dose (LD50) and 90% lethal dose (LD90) values approximately two times higher than those observed with DDP alone. DDP-P.HCl diluted in water and administered intraperitoneally (IP) on day 1 and on days 1 and 5 to BDF1 mice bearing P388 leukemic cells produced 33% and 50% cure rates, respectively, at the maximum tolerated dose (16 mg/kg for the single administration and 10 mg/kg given on days 1 and 5). In contrast, under the same conditions, the cure rates obtained with DDP alone (10 mg/kg for the single administration and 8 mg/kg given on days 1 and 5) were 17% and 9%, respectively. Protection from DDP nephrotoxicity seems to be the explanation for the higher doses of DDP that mice can tolerate when DDP is given simultaneously with P.HCl. In fact, the increased blood urea nitrogen (BUN) levels observed 4-7 days following a single IP administration of DDP (8 or 16 mg/kg), as well as the tubular degenerative changes detected by light microscopy, were not observed when the same doses of DDP were given simultaneously with P.HCl. Since DDP nephrotoxicity is known to be reduced when the drug is diluted in 0.9% NaCl solution, we compared the combinations DDP-P.HCl in water, and DDP and DDP-P.HCl in 0.9% NaCl solution. The antitumor activity of DDP diluted in water and administered with P.HCl was similar to that observed in mice treated with DDP alone diluted in 0.9% NaCl solution. However, further improvement of the therapeutic index was achieved after the administration of DDP P.HCl diluted in 0.9% NaCl solution; this regimen produced a cure rate of 67% (12 of 18 animals). The clinical relevance of these findings is strengthened by the observation that similar results were obtained when P.HCl was given by the intravenous route. PMID- 2319612 TI - National boards and the minority medical student. PMID- 2319611 TI - Rising incidence of breast cancer: relationship to stage and receptor status. AB - We used the population-based tumor registry of Kaiser Permanente in the United States (Portland, OR) to analyze breast cancer incidence from 1960 to 1985. Overall, incidence rose 45% during this period. The largest increases occurred in women 60 years of age or older (74%) and in those 45-59 (36%). The rate in women aged 20-44 has remained essentially unchanged. Localized and regional disease showed similar increases. Review of medical records revealed that only a small portion of this increase was likely to result from increased screening activities. From the increased availability of receptor assays in a large proportion of cases since the mid-1970s, we observed that incidence of estrogen receptor-negative cancers rose 22%-27% between the mid-1970s and the mid-1980s. In contrast, incidence of estrogen receptor-positive tumors increased an average of 131% in the same period, perhaps implicating hormonal factors in the rising incidence of breast cancer. PMID- 2319613 TI - Iodine 125 interstitial irradiation for localized prostate cancer. AB - We present the technique, complications, and 5-year results of transperineal percutaneous template permanent interstitial iodine 125 endocurietherapy of localized prostate cancer in 85 treated patients. The 5-year outcome appears similar to that of external beam radiation therapy or radical surgery, but the iatrogenic mortality, morbidity, treatment time, and hospitalization are significantly reduced. PMID- 2319614 TI - Enhancing magnetic resonance images using water bags. AB - Fascial planes between tissues are separated by connective tissue, fat, and blood vessels. Magnetic resonance imaging displays surface anatomy and soft tissues. Our team has been successful in demonstrating brachial plexus nerves as a model of magnetic resonance anatomy. Radiologists have devised methods to increase the resolution of images by suppressing noise and increasing the sharpness of the image. We added water bags to a 0.3 tesla permanent magnet suppressing the noise and increasing the signal to image our patients. The images proved to be sharper. PMID- 2319615 TI - Computer assisted linear accelerator shielding calculations. PMID- 2319616 TI - Jaundice and hepatorenal syndrome associated with cytosine arabinoside. AB - A young man receiving high dose cytosine arabinoside (3g/m2 every 12 hours) for promyelocytic leukemia developed rapidly increasing hyperbilirubinemia and hepatorenal syndrome. The patient had been treated previously with courses of standard dose cytosine arabinoside without hepatic or renal complications. His condition rapidly deteriorated, and he required hemodialysis. The total bilirubin increased to 45.4 mg/dL, but alkaline phosphatase remained normal. Twelve days after starting chemotherapy, the patient died of hepatorenal failure. Liver necropsy revealed mild bile stasis and microvesicular steatosis. We suspect high dose cytosine arabinoside played a major role in causing impairment of bilirubin transport within the hepatocyte in this patient. PMID- 2319617 TI - Mediastinal radiographic abnormality caused by anomalous venous drainage: how often is it seen in Afro-Americans? AB - An abnormal superior mediastinal density seen on a chest x-ray led to computerized tomography scan detection of an enlarged azygous vein produced by anomalous embryologic development of the inferior vena cava. This potentially clinically important abnormality is uncommon and statistics indicating its frequency are best available from the Japanese. In addition to alerting clinicians to this abnormality, a plea is made for review of autopsy series in Afro-Americans by pathologists in order to determine potential risks in a variety of surgical procedures. PMID- 2319618 TI - Purification of an endogenous 68 kD inhibitor of calcium-activated neutral proteinase (CANP) from bovine brain: immunoblot identification and characterization. AB - A calcium-activated neutral proteinase (CANP)-specific endogenous inhibitor (calpastatin) was purified from bovine brain by successive column chromatography. The purified inhibitor exhibited a major band on sodium dodecylsulfate polyacrylamide gel electrophoresis with an approximate molecular weight of 68 kD. The polyclonal antisera raised to the inhibitor strongly reacted with the 68 kD protein band. Two lightly stained bands approximately 55-68 kD and 120-130 kD were also recognized by the inhibitor antiserum. The inhibitor specifically inhibited CANP activity and the half-maximal inhibition was found with 75 ng of calpastatin per 1 micrograms of CANP in a final volume of 125 microliters. Cathepsin B and papain were not inhibited by the inhibitor, while trypsin and chymotrypsin were inhibited to some extent. The inhibitor formed a complex with CANP and the inactive complex was dissociated into active fractions of enzyme and calpastatin in the presence of EGTA. PMID- 2319619 TI - Asymmetry of interhemispheric responses evoked in the prefrontal cortex of the rat. AB - Interhemispheric responses of anesthetized rats were evoked in the prefrontal cortex of both cerebral hemispheres by electric stimulation of the homologous contralateral cortical region. Fatigability of interhemispheric responses to repetitive stimulation was lower in the right prefrontal cortex. Besides, responses recorded in the right hemisphere exhibited greater amplitude increments to double-shock stimulation. No significant differences in rheobase, chronaxie, and threshold current were observed when comparing responsiveness of both prefrontal cortices to single stimuli. Results suggest that brain lateralization in the rat could depend, in part, on synaptic functional asymmetries of the prefrontal cortex. PMID- 2319620 TI - Expression of heat shock genes (hsp70) in the mammalian brain: distinguishing constitutively expressed and hyperthermia-inducible mRNA species. AB - The mammalian genome contains both constitutively expressed and heat-shock inducible members of the hsp70 gene family. Riboprobes derived from members of these two classes of heat shock genes were utilized in Northern blot studies to analyze brain mRNA isolated from control rabbits and rats and from animals subjected to hyperthermic treatment. A riboprobe derived from a constitutively expressed hsp70 gene detected a 2.5 kilobase (kb) mRNA in brain tissue from control rabbits and a 2.3 kb mRNA species in control rat brain. These brain mRNAs showed little change in abundance in animals which were subjected to hyperthermic treatment. A riboprobe derived from a heat-shock-inducible hsp70 gene detected an abundant 2.7 kb brain transcript in hyperthermic rabbits which was not apparent in control animals. A time course study revealed that the induction of this mRNA species was transient and paralleled the rise and fall in body temperature. Peak induction was observed at 1 hr. The level of this message had greatly decreased by 5 hr and only trace levels were present at 10 and 24 hr. In the rat brain the induced hsp70 mRNA species was slightly larger than that observed in rabbit (2.9 kb vs. 2.7 kb). The riboprobe which detected the hyperthermia-inducible mRNA species was highly specific and did not cross react to the constitutively expressed mRNA species under the conditions employed in the Northern blot studies. PMID- 2319621 TI - Dual-label retrograde transport: CNS innervation of the mouse thymus distinct from other mediastinum viscera. AB - Two different retrogradely transported tracers were identified and used to distinguish between the innervation of the thymus gland and the innervation of adjacent tissues residing within the mouse mediastinum. To determine the best procedure for peripheral dual-labeled retrograde transport, several different tracers, vehicles, and injection protocols were developed and/or tested. In the periphery, it proved ineffective to use Rhodamine latex microspheres (Luma-Fluor) as a retrograde transport agent. Horseradish peroxidase (HRP) suspended in the water-soluble carrier KY Jelly and Fluoro-Gold (FG) in an aqueous solution was the most effective combination of retrograde transport tracers. Equivalent doses of each of these tracers were determined, and injections of HRP or FG into the thymus and the esophagus produced distinct and separate patterns of labeled neurons in the spinal cord or brain stem. Throughout these CNS areas, some neurons contained both tracers suggesting that 1) these areas are innervated by neurons that give rise to collaterals to these tissues, 2) that the retrograde tracers are transported by nerves that innervate the lymphatics of the mediastinum, and/or 3) that some diffusion of the tracers occurs from the test organs and tissues to other organs and tissues of the mediastinum. PMID- 2319622 TI - Expression of transfected genes by differentiated, postmitotic neurons and photoreceptors in primary cell cultures. AB - We report here that differentiated, primary, postmitotic neurons and photoreceptors in cultures obtained from embryonic chicks can express foreign genes after transfection by the calcium phosphate method. A variety of viral promoters were tested by using either beta-galactosidase or chloramphenicol acetyltransferase as reporter genes. Histochemical and immunocytochemical analysis showed beta-galactosidase expression by both neurons and photoreceptors. As commonly observed with dividing cells, transfection efficiencies showed inter experimental variability, with efficiencies ranging from 2% to 20% using the same plasmid. On the other hand, intra-experimental variability between replicate dishes was much smaller. Analysis using the highly sensitive enzymatic assay for chloramphenicol acetyl transferase (CAT) showed that all of the promoter/enhancers-CAT constructs tested, with the exception of a construct containing the Maloney sarcoma virus promoter, led to the expression of detectable activity when transfected into cultured retinal cells. The calcium phosphate treatment used for cell transfection did not show detectable effects on overall cell survival, although it caused selective decreases in some metabolic activities of the cells. The studies demonstrate that it is possible to obtain expression of genes transfected into primary, postmitotic neuronal cells. PMID- 2319623 TI - Cultured neurons release an inhibitor of astroglia proliferation (astrostatine). AB - Using in vitro techniques, we looked for a possible downregulation of rat astroglia proliferation by neuronal cells. We demonstrate that medium conditioned by 7-day-old rat cerebellar granule neurons or by 16-day-old rat embryo hippocampal neurons strongly inhibits the proliferation of cultured astroglial cells. Two neuronal cell lines, the PC12 rat pheocromocytoma and the neuro 2A (N2A) murine neuroblastoma also release such an activity. This release in N2A conditioned medium (CM) occurs when the cells are at high density and show a low proliferation rate. This activity is present in media conditioned by neuronal cells, but not in media conditioned by normal astrocytes, by two glioma cell lines, or by one fibroblastic cell line. This proliferation inhibitor addresses normal astrocytes: the proliferation of two glioma cell lines, of a fibroblastic cell line, and of the two neuronal cell lines (PC12, N2A) is not inhibited by N2A CM. Moreover, this activity is directed against type 1 astrocytes, but not against type 2. Using three different assays, we demonstrate that DNA synthesis by astroglial cells is inhibited. N2A CM has no cytotoxic effect on astrocytes and does not modify their overall protein synthesis. Using affinity and gel filtration chromatography, we show that this activity is associated with a protein whose molecular weight ranges between 15 and 20 kDa. The possible relationship between this N2A cell-derived astroglia proliferation inhibitor and other types of potential glial proliferation inhibitors has been investigated. A brain glycoprotein immunologically related to epidermal growth factor receptor (EGFR) was reported to inhibit astroglial cell proliferation in vitro. Using polyclonal and monoclonal antibodies against EGFR, we were unable to immunoprecipitate the astrocyte proliferation inhibitor in N2A CM or to demonstrate by immunoblotting the presence of an EGFR-like immunoreactivity in the N2A CM or in the active chromatographic fractions of N2A CM. Transforming growth factor beta (TGF beta) is a well-known modulator of the proliferation of various cell types and was shown to be present in N2A CM. Using a polyclonal anti TGF beta antibody that recognizes TGF beta on Western blots of N2A CM, we were unable to immunoprecipitate the astrocyte proliferation inhibitor of N2A CM. It seems thus far that the neuronal astroglia proliferation inhibitor is a new protein for which we propose the name astrostatine. PMID- 2319624 TI - Phorbol ester-induced change in astrocyte morphology: correlation with protein kinase C activation and protein phosphorylation. AB - Treatment with 300 nM phorbol 12-myristate 13-acetate (PMA) transforms polygonal shaped cultured astrocytes into process-bearing cells and produces a shift in protein kinase C (PK-C) from the cytosol to the membrane. Exposure to PMA also produces increases in the phosphorylation of several proteins including vimentin, glial fibrillary acidic protein (GFAP), an acidic 80,000 molecular weight protein, and two 30,000 molecular weight proteins (pI 5.5 and 5.7). The effects of PMA on the translocation of PK-C and on protein phosphorylation precede the PMA-induced changes in astrocyte morphology, and a close correlation exists between the concentration of PMA necessary to elicit half-maximal and maximal effects on the shift of PK-C to the membrane and on protein phosphorylation. In addition, the PMA-induced alterations in cell morphology are not permanent, and within 24 hr after PMA treatment the cells have reverted almost to their original morphology. A second exposure to PMA at this time fails to elicit further change in cell shape and is also incapable of producing increases in the phosphorylation of proteins. It was determined that there is little, if any, PK-C present in these PMA-pretreated cells. The morphological responsiveness to PMA gradually returns in 5 to 8 days after the initial treatment with PMA, and this is accompanied by the recovery of PK-C activity and the phosphorylation response. Therefore, these studies suggest that the effect of PMA on astrocyte morphology is mediated by the activation of PK-C and subsequent protein phosphorylation. PMID- 2319625 TI - Development of neurophysin-containing neurons in primary cultures of rat hypothalami is related to the age of the embryo: morphological study and comparison of in vivo and in vitro neurophysins, oxytocin, and vasopressin content. AB - The morphological development of immunocytochemically identified neurophysin neurons and the evolution of neuropeptide content (neurophysins, vasopressin, and oxytocin) were studied in primary cultures of hypothalami obtained from 15- to 19 day-old embryos. According to their perikaryal surface, two populations of neurons were distinguished: large and small cells. Full development (defined by the perikaryal surface) of these neurons was reached at day 21 only in cultures from 15- or 16-day-old embryos. These two types of neurons may correspond to the magnocellular and parvocellular neurons described in vivo. Total neurophysins, vasopressin, and oxytocin content were measured by specific radioimmunoassays. Ontogeny of neurophysins and vasopressin showed a good correlation between cells cultured from 15- to 16-day-old embryos and hypothalami from age-matched rats. However, oxytocin was never detected in any of the cultures whatever the age of the embryos. Under our experimental conditions, hypothalamic primary cultures from 15- to 16-day-old embryos therefore appeared to be suitable for studying the differentiation and regulation of neurophysin- and vasopressin-containing neurons. PMID- 2319626 TI - Regulation of apolipoprotein E gene expression after injury of the rat sciatic nerve. AB - The expression of apolipoprotein E (apo E) is dramatically increased following peripheral nerve injury. This increased expression has been postulated to be negatively influenced by unknown mechanisms during subsequent axonal regeneration (Muller et al.: Science 228:499-501, 1985). The present study investigates the role of the regenerating axon in regulating apo E gene expression in two experimental paradigms which permit or prevent axonal regeneration in the adult rat sciatic nerve--the crush or permanent transection injuries. The nerves in these two models undergo axonal degeneration, demyelination, and Schwann cell proliferation; however, subsequent axonal regeneration and remyelination occur only in the distal segment of the crush-injured and not in the permanently transected nerve. The steady-state levels of apo E mRNA in both models increase sharply between 1 and 4 days and reach a maximum level at 12-14 days, which did not change significantly between 14 and 35 days after injury. No significant difference is observed in the steady-state levels of apo E mRNA between the crushed and permanently transected nerves as a function of time after injury. The steady-state protein level of apo E in the endoneurial segments initially increases, peaks at 14-21 days, and then decreases between 35 and 60 days after injury in both models. In contrast, the rate of newly translated and secreted apo E significantly increases by fourfold (P less than 0.005) between 35 and 60 days after permanent transection whereas it does not significantly differ at these times after crush injury. The increased rate of translation and secretion of apo E after transection compared to the constant rate observed after crush injury, together with the comparable steady-state levels of apo E mRNA and protein in both models, suggests translational or post-translational control, but not transcriptional and/or posttranscriptional control, by the regenerating axons. Furthermore, the increasing rate of biosynthesis and secretion of apo E after permanent transection concomitant with the decreasing steady-state levels of the protein suggests that apo E is either removed from the endoneurium or subsequently utilized or degraded by mechanisms that are independent from nerve regeneration. PMID- 2319627 TI - Neurite outgrowth promoting activity of G4 and its inhibition by monoclonal antibodies. AB - The chick G4 molecule is a cell surface glycoprotein which is a member of the L1/NILE/NgCAM/8D9 group of neural cell adhesion molecules. Polyclonal antisera against G4 have been shown to decrease sympathetic neurite outgrowth on sympathetic axons and to de-bundle retinal axons growing on a tectal membrane substrate. We have extended the specificity of these results by showing that a panel of monoclonal antibodies against G4 is also effective in reducing sympathetic neurite outgrowth on sympathetic axons. Furthermore, purified G4 adsorbed onto an inert substrate promotes extensive neurite outgrowth. Monoclonal antibodies to G4 completely inhibit the activity of purified G4. These data show that G4 is a cell surface neurite outgrowth promoting molecule, a function which was first suggested by antibody perturbation experiments and now is confirmed directly. PMID- 2319628 TI - Developmental expression of glial fibrillary acidic protein mRNA in the rat brain analyzed by in situ hybridization. AB - Glial fibrillary acidic protein (GFAP) accumulates in astrocytes during development. We have characterized the increase in GFAP mRNA during development of the rat brain by using Northern blotting and in situ hybridization histochemistry and have found a caudal to rostral gradient of expression, consistent with overall brain maturation. GFAP mRNA was first observed at embryonic day 16 (E16) in the glial limitans of the ventral hindbrain. During brain development message levels increased rostrally and by postnatal day 5 (P5) the entire glial limitans showed a positive signal which persisted into adulthood. GFAP mRNA was also found to accumulate in a caudal to rostral direction within the Purkinje cell layer of cerebellum beginning shortly after birth. By P5 the entire layer was positive and signal in this region could be localized to Bergmann glia by P15. A transient elevation in GFAP mRNA was apparent during the second postnatal week in cerebellum and cerebrum. Using in situ hybridization, a peak in message levels was observed at P15 and could be localized primarily to the deep white matter of cerebellum, to the corpus callosum, and to certain hippocampal fiber tracts. The pattern of GFAP expression in these regions is consistent with the differentiation of interfascicular glia and the appearance of type-2 astrocytes during the initial events of myelination. GFAP mRNA levels in white matter were greatly reduced in the adult. The pronounced regional differences in GFAP mRNA expression during development may reflect the differentiation of subpopulations of astrocytes. PMID- 2319629 TI - Association of iron-containing astrocytes with dopaminergic neurons of the arcuate nucleus. AB - Specialized astrocytes, identified by cytoplasmic granules that are electron dense and vividly stained by toluidine blue due to the presence in the granules of SH molecules and molecules of iron, have long been known to be present within the arcuate nucleus of the hypothalamus. Their function, however, is obscure. To determine whether or not these specialized astrocytes are in contact with dopaminergic neurons, rat brain sections were stained to detect tyrosine hydroxylase (TH) immunoreactive neurons by immunocytochemistry and were examined by both light and electron microscopy. Iron-rich astrocytes were located in the same general portion of the arcuate nucleus as were TH+ neurons, and most appeared closely associated with TH+ structures (somas, dendrites, and fibers) at the light-microscopic level. At the ultrastructural level, close contact between TH + neurons and processes of iron-rich glia was confirmed. This unique anatomical association suggests a functional relationship between the two cell types that may be related to unusual histochemical features of both cell types and/or to the location of these cells in an area with a highly permeable blood brain barrier. PMID- 2319630 TI - Coexpression of lactosyl and gangliotetraosyl gangliosides in rat cerebellar radial glial cells in culture. AB - The expression of gangliosides of the lactosylceramide (LC) and of the gangliotetraosylceramide (GTC) series on the surface of cells from rat embryonic cerebellar tissue was investigated by double-color indirect immunofluorescence. GD3 was assumed to be representative of LC and was detected using a specific monoclonal antibody. GM1 was assumed to be representative of GTC and was detected using the binding of cholera toxin followed by the binding of cholera toxin antibodies. The expression of polysialosylated GTC (polysialosyl-GTC) was detected using the cholera toxin-cholera toxin antibody experimental approach after conversion of polysialosyl-GTC to GM1 by treatment of the cells with neuraminidase. To distinguish the major neural cell types present in the cultures the expression of the following cell type-specific markers was investigated: neuron-specific enolase and microtubule-associated protein-2 (MAP-2) as probes for neuronal cells and the intermediate filament protein glial fibrillar acidic protein (GFAP) as a probe for astroglial cells. More than 80% of cells dissociated from cerebellar tissue of 15-day-old rat embryos (E15) are positive for the expression of GD3 and about 50% for the expression of GM1 and polysialosyl-GTC, but most are negative for the expression of neuron-specific enolase, MAP-2, and GFAP. After culturing for 4 days (E15 + 4) most cells that show characteristics of neuronal cells are positive for the expression of polysialosyl-GTC and "inactivate" the expression of GD3. Most cells with characteristics of radial and stellate glial cells are also positive for the expression of polysialosyl-GTC, but unlike neuron-like cells, they do not "inactivate" the expression of GD3. PMID- 2319631 TI - Construction of best confidence intervals for half-lives. AB - This paper presents a method of determining a confidence interval for the drug half-life based on statistical properties of the estimates of the disappearance rate constant of the drug. This interval is shown to be of minimum length which indicates it is a more precise estimate than others currently in use. A computer program to construct these intervals is available upon request. PMID- 2319632 TI - Pharmacokinetics and plasma protein binding of gentamicin in Bubalus bubalis calves. PMID- 2319633 TI - The cardiorespiratory effects of intrathecal xylazine in the conscious rabbit. AB - The alpha 2 agonist xylazine produced a dose-dependent decrease in mean arterial blood pressure in conscious rabbits when injected intrathecally (i.t.) through a cannula previously implanted under general anaesthesia. Intrathecal administration of 200 and 400 micrograms of xylazine produced a significant reduction in arterial blood pressure from control values (maximum depressions of 25% and 33%, respectively). There was little effect on cardiac output and arterial carbon-dioxide tension and no effect on respiratory rate, arterial oxygen tension and pulse rate. Intrathecal injection of 100 microliters of 0.9% saline had no effect. Intravenous (i.v.) tolazoline (0.5 mg/kg) abolished xylazine-induced hypotension (200 micrograms) in four rabbits. Contrast radiography revealed that 100 microliters of solution injected i.t. in anaesthetized rabbits spread distally over eight vertebral spaces. There was little rostral spread. It was concluded that xylazine-induced hypotension following i.t. injection was due to local activation of alpha 2 adrenoceptors present in the thoracic spinal cord. It is postulated that spinal alpha 2 adrenoceptors may play an important role in the hypotension recorded in animals after parenteral injection of xylazine. PMID- 2319634 TI - Plasma estradiol-17 beta concentrations in the cow during induced estrus and after injection of estradiol-17 beta benzoate and estradiol-17 beta cypionate--a preliminary study. AB - Plasma estradiol-17 beta concentrations were investigated in cows during induced estrus and after an intramuscular injection of 10 mg of estradiol-17 beta benzoate and estradiol-17 beta cypionate to determine a withdrawal period for both preparations. After the estradiol-17 beta benzoate injection, the plasma estradiol-17 beta concentration was higher than the physiological maximum of 24 pg/ml obtained during induced estrus for a period of 114 +/- 10 h (mean +/- SEM). For estradiol-17 beta cypionate the corresponding value was 170 +/- 17 h (mean +/ SEM). A withdrawal period of 7 days for the benzoate ester and of 10 days for estradiol-17 beta cypionate is therefore proposed. These results were confirmed by biopsies taken at the injection site 8 and 15 days after the injection of estradiol-17 beta benzoate and estradiol-17 beta cypionate, respectively. In these biopsies no residues of estradiol-17 beta nor of its esters could be detected. PMID- 2319635 TI - Effects of experimentally induced Streptococcus suis infection on the pharmacokinetics of penicillin G in pigs. AB - The pharmacokinetics of potassium penicillin G were studied in both healthy (n = 8) and experimentally Streptococcus-suis-infected (n = 6) pigs following intramuscular administration (15,000 iu/kg). Streptococcus-suis infection was induced artificially in young cross-bred pigs by subcutaneous inoculation with 9 x 10(8) to 10(9) colony-forming units of S. suis. The rectal temperature of infected pigs was significantly increased (P less than 0.01) before penicillin G injection and this was maintained for 8 h after the drug was given. Other clinical symptoms were also present. The serum concentration-time data for penicillin were found to fit a one-compartment open model with first-order absorption in the two groups of pigs. Significant changes were not observed between healthy and diseased pigs in following parameters: A, Ka, Ke and Tmax. However, in diseased pigs, significant increases (P less than 0.01) were found in Vd and ClB, and significant decreases (P less than 0.01) in Cmax and AUC occurred. The increased body clearance (ClB) and greater apparent volume of distribution (Vd) of penicillin G could partly explain why the serum values of the drug were much lower in diseased pigs than in healthy pigs. PMID- 2319636 TI - Chlortetracycline in swine--bioavailability and pharmacokinetics in fasted and fed pigs. AB - Chlortetracycline hydrochloride was administered intra-arterially (11 mg/kg) and as an oral drench (33 mg/kg) to ten 21.0-31.5-kg pigs. Five of the pigs were fasted 18 h prior to dosing and five of the pigs were fed ad libitum prior to dosing. The mean volume of distribution determined by area-under-the-curve calculations for the fasted pigs (0.967 +/- 0.210 l/kg) was significantly less (P less than 0.05) than the mean volume of distribution for the fed pigs (1.39 +/- 0.31 l/kg). Mean total body clearance of the drug was also significantly less (P less than 0.05) in the fasted pigs (0.165 +/- 0.055 l/kg/h) as compared to the fed pigs (0.307 +/- 0.053 l/kg/h). The elimination constants (beta) were not found to be statistically different (P less than 0.05): 0.1811 +/- 0.0057 for the fasted pigs; 0.2260 +/- 0.0461 for the fed pigs. The bioavailability for both groups was similar; 19.12 +/- 8.3% for the fasted pigs and 17.88 +/- 5.3% for the fed pigs. In a second experiment three groups of six pigs which weighed 34.5-44.1 kg were fed a corn-soy diet ad libitum. The rations were fortified with chlortetracycline at 100, 400 or 1000 mg chlortetracycline hydrochloride/kg feed. Chlortetracycline concentrations were determined in plasma samples collected over a 6-day period. Plasma chlortetracycline concentrations reach a plateau within 24 h after initial access to the trial diets and were highly correlated with the dose of the drug consumed (r2 = 0.97). PMID- 2319637 TI - Copper salicylate and copper phenylbutazone as topically applied anti inflammatory agents in the rat and horse. AB - Topically applied copper phenylbutazone, phenylbutazone, copper salicylate, salicylate and dimethylsulfoxide glycerol (80:20) were investigated as anti inflammatory agents in rats and horses. Dimethylsulfoxide and glycerol (80:20) or dimethylsulfoxide, ethanol and glycerol (60:20:20) were used as the drug solvents. Subcutaneously administered carrageenin was used to induce inflammatory oedema, either in the paws of rats or the alar fold of the horse. The severity of the oedema and the anti-inflammatory effect of the drugs were assessed by measuring changes in the paw or alar-fold diameters. Copper salicylate and copper phenylbutazone were effective inhibitors of the inflammatory oedema in both species, but dimethylsulfoxide:glycerol (80:20) was not. In the rat, copper salicylate and copper phenylbutazone were superior anti-inflammatory agents compared to either salicylate or phenylbutazone, respectively. Following the topical application of four times the recommended daily dose of copper phenylbutazone to the horse for 5 days, minor skin irritation occurred and trace concentrations of phenylbutazone (maximum 0.6 microgram/ml) and negligible concentrations of oxyphenbutazone and gamma-hydroxyphenylbutazone were detected in the plasma. PMID- 2319638 TI - Spiramycin concentrations in plasma and genital-tract secretions after intravenous administration in the ewe. AB - Uterine infections are associated with reduced fertility in ruminant species. Spiramycin is a macrolide antibiotic potentially active against most of the microorganisms isolated from secretions of infected genital tracts. The present work investigated the ability of systemically administered spiramycin to enter genital secretions, by determining the disposition kinetics of the antibiotic in both plasma and uterine genital secretions. Five healthy ovariectomized ewes were given a single intravenous (i.v.) injection of spiramycin, at a dose of 20 mg/kg. Plasma and genital secretion samples were collected at predetermined intervals for 5 days post-injection. Blood was collected from the jugular vein while mucus was obtained by inserting polyurethane sponges into the vagina. The spiramycin concentration peak in genital-tract secretions was obtained 2.53 +/- 0.63 h after the i.v. administration. The mean residence time was significantly longer (P less than 0.01) in the mucus (18.31 +/- 3.24 h) than in plasma (6.99 +/- 2.53 h). An average mucus to plasma ratio of 7.87 +/- 3.00 was calculated from the area under concentration-time curves covering the period under study. These data indicate that after systemic administration to ewes, spiramycin is rapidly found in genital-tract secretions, at concentrations which are sufficiently high and persistent to suggest its use in the treatment of post-partum uterine infections. PMID- 2319639 TI - Pharmacokinetics of tinidazole in the horse. AB - Serum tinidazole concentrations were monitored in five clinically healthy adult horses after intravenous (i.v.) and oral administration of the drug (15 mg/kg and 25 mg/kg, respectively). After i.v. administration, the mean residence time was 7.0 h, the elimination half-life 5.2 h and the body clearance rate 1.6 ml/min/kg. The distribution volume was found to be 660 ml/kg. After oral administration, the mean residence time was 8.5 h, the absorption half-life 1.1 h and the bioavailability essentially 100%. In view of the in-vitro sensitivities of various anaerobic bacteria, a dosage of 10-15 mg/kg of tinidazole, orally, at 12 h intervals, can be recommended for the treatment of anaerobic infections in horses. PMID- 2319640 TI - The pharmacokinetics of chloramphenicol in plasma and saliva of dairy cows. AB - In the present study the pharmacokinetics of chloramphenicol were investigated in bovine plasma and saliva. The method of detection of chloramphenicol, a radio immunoassay, requires only small sample volumes, no further clean-up, and a large number of samples can be processed simultaneously. This enabled the collection of a larger number of samples over a longer period of time than in previous studies. The intention was to obtain a complete pharmacokinetic profile of chloramphenicol, to evaluate it according to common open-compartment models, and to compare it with the results of previous studies. The radio-immunoassay results were confirmed by analysing a number of samples distributed over the concentration range of interest by a gas-chromatographic method with electron capture detection. The suitability of saliva was evaluated as a possible means of monitoring compliance with the ban on chloramphenicol in the Federal Republic of Germany in milk-producing animals. PMID- 2319641 TI - The influence of furosemide on plasma elimination and urinary excretion of drugs in standardbred horses. AB - A study of the effects of intravenous administration of either 150 mg or 250 mg of furosemide to standardbred mares pre-treated with other drugs was undertaken to determine whether a unique pattern of drug elimination into urine and from plasma for each compound occurred. Furosemide significantly reduced the plasma concentrations of codeine compared to control 2-6 h after furosemide administration. In contrast, the plasma concentrations of theophylline, phenylbutazone, pentazocine, guaifenesin and flunixin were not markedly altered by furosemide. In the case of acepromazine, clenbuterol and fentanyl, the data generated were insufficient to state with certainty whether or not furosemide affected the plasma concentrations of these three drugs. A significant reduction was noted in the urinary concentrations of guaifenesin, acepromazine, clenbuterol, phenylbutazone, flunixin, fentanyl and pentazocine within 1-4 h of furosemide administration. The urinary concentrations of theophylline remained reduced as long as 8 h after furosemide injection. Furosemide administration to horses pre-treated with codeine resulted in depression of urinary morphine concentrations 2-4 h and 9-12 h after furosemide injection. A lower furosemide dose (150 mg) produced changes in drug urinary excretion and plasma elimination equivalent to the higher dose (250 mg). It is evident that furosemide affects the urinary and plasma concentrations of other co-administered drugs but not in a predictable fashion, which limits the extrapolation of these results to as yet untested drugs. PMID- 2319642 TI - Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals. AB - The sera from 16 individuals infected with the human immunodeficiency virus (HIV) at different clinical stages were evaluated for antibody-dependent neutralization and/or enhancement of infectivity by HIV. The HIV isolate from each individual (homotypic) and established laboratory strains showing broad cellular host range and cytopathicity were used. All sera could neutralize one of the laboratory passaged isolates, whereas only two could neutralize the corresponding homotypic strain. Seven homotypic isolates were enhanced by serum from the respective individual. This activity was primarily observed in patients with acquired immune deficiency syndrome. Moreover, the tropism for macrophages of four of these seven viral isolates was found to be enhanced by the homotypic sera. Finally, sequential pairs of HIV and sera obtained from five HIV-infected individuals with different clinical progression were studied over time. The enhancing activity of three of the five sera appeared to increase over time, indicating changes in both the host virus population and the type of antibodies produced. These results suggest that enhancing antibodies contribute to the spread and pathogenesis of HIV in vivo. They emphasize the necessity of studying further the association of enhancing antibodies and disease progression in infected individuals. PMID- 2319643 TI - Mutagenesis of the 3' nontranslated region of Sindbis virus RNA. AB - A cDNA clone from which infectious RNA can be transcribed was used to construct 42 site-specific mutations in the 3' nontranslated region of the Sindbis virus genome. The majority of these mutations were made in the 3'-terminal 19 nucleotide conserved sequence element and consisted of single nucleotide substitutions or of small (1 to 8) nucleotide deletions. An attempt was made to recover mutant viruses after transfection of SP6-transcribed RNA into chicken cells. In most cases, viable virus was recovered, but almost all mutants grew more poorly than wild-type virus when tested under a number of culture conditions. In the case of mutations having only a moderate effect, the virus grew as well as the wild type but was slightly delayed in growth. Mutations having a more severe effect led to lower virus yields. In many cases, virus growth was more severely impaired in mosquito cells than in chicken cells, but the opposite phenotype was also seen, in which the mutant grew as well as or better than the wild type in mosquito cells but more poorly in chicken cells. One substitution mutant, 3NT7C, was temperature sensitive for growth in chicken cells and severely crippled for growth in mosquito cells. Insertion mutations were also constructed which displaced the 19-nucleotide element by a few nucleotides relative to the poly(A) tail. These mutations had little effect on virus growth. Deletion of large regions (31 to 293 nucleotides long) of the 3' nontranslated region outside of the 19-nucleotide element resulted in viruses which were more severely crippled in mosquito cells than in chicken cells. From these results, the following principles emerge. (i) The entire 3' nontranslated region is important for efficient virus replication, although there is considerable plasticity in this region in that most nucleotide substitutions or deletions made resulted in viable virus and, in some cases, in virus that grew quite efficiently. Replication competence was particularly sensitive to changes involving the C at position 1, the A at position 7, and a stretch of 9 U residues punctuated by a G at position 14. (ii) The panel of mutants examined collectively deleted the entire 3' nontranslated region. Only mutants in which 8 nucleotides in the 3' terminal 19 nucleotides had been deleted or in which the 3' terminal C was deleted were nonviable. Although the 3' terminal C was essential for replication, it could be displaced by at least 7 nucleotides from its 3' terminal position adjacent to the poly(A) tract.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2319644 TI - Evolution of the nucleoprotein gene of influenza A virus. AB - Nucleotide sequences of 24 nucleoprotein (NP) genes isolated from a wide range of hosts, geographic regions, and influenza A virus serotypes and 18 published NP gene sequences were analyzed to determine evolutionary relationships. The phylogeny of NP genes was determined by a maximum-parsimony analysis of nucleotide sequences. Phylogenetic analysis showed that NP genes have evolved into five host-specific lineages, including (i) Equine/Prague/56 (EQPR56), (ii) recent equine strains, (iii) classic swine (H1N1 swine, e.g., A/Swine/Iowa/15/30) and human strains, (iv) gull H13 viruses, and (v) avian strains (including North American, Australian, and Old World subgroups). These NP lineages match the five RNA hybridization groups identified by W. J. Bean (Virology 133:438-442, 1984). Maximum nucleotide differences among the NPs was 18.5%, but maximum amino acid differences reached only 10.8%, reflecting the conservative nature of the NP protein. Evolutionary rates varied among lineages; the human lineage showed the highest rate (2.54 nucleotide changes per year), followed by the Old World avian lineage (2.17 changes per year) and the recent equine lineage (1.22 changes per year). The per-nucleotide rates of human and avian NP gene evolution (1.62 x 10( 3) to 1.39 x 10(-3) changes per year) are lower than that reported for human NS genes (2.0 x 10(-3) changes per year; D. A. Buonagurio, S. Nakada, J. D. Parvin, M. Krystal, P. Palese, and W. M. Fitch, Science 232:980-982, 1986). Of the five NP lineages, the human lineage showed the greatest evolution at the amino acid level; over a period of 50 years, human NPs have accumulated 39 amino acid changes. In contrast, the avian lineage showed remarkable conservatism; over the same period, avian NP proteins changed by 0 to 10 amino acids. The specificity of the H13 NP in gulls and its distinct evolutionary separation from the classic avian lineage suggests that H13 NPs may have a large degree of adaptation to gulls. The presence of avian and human NPs in some swine isolates demonstrates the susceptibility of swine to different virus strains and supports the hypothesis that swine may serve as intermediates for the introduction of avian influenza virus genes into the human virus gene pool. EQPR56 is relatively distantly related to all other NP lineages, which suggests that this NP is rooted closest to the ancestor of all contemporary NPs. On the basis of estimation of evolutionary rates from nucleotide branch distances, current NP lineages are at least 100 years old, and the EQPR56 NP is much older.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2319645 TI - Expression strategy of a phlebovirus: biogenesis of proteins from the Rift Valley fever virus M segment. AB - The middle (M) RNA segment of Rift Valley fever virus (RVFV) encodes four proteins: the major viral glycoproteins G2 and G1, a 14-kilodalton (kDa) protein, and a 78-kDa protein. These proteins are derived from a single large open reading frame (ORF) present in the virus-complementary M-segment mRNA. We used recombinant vaccinia viruses in which sequences representing the M-segment ORF were engineered as a surrogate system to study phlebovirus protein expression. To investigate the translational initiation codon requirements for synthesis of these proteins, we constructed a series of vaccinia virus recombinants containing specific sequence changes which eliminated select ATG codons found in the region of the ORF preceding the mature glycoprotein-coding sequences (the preglycoprotein region). Examination of phleboviral proteins synthesized in cells infected with these vaccinia virus recombinants clearly showed that the first ATG of the ORF was required for the production of the 78-kDa protein, while synthesis of the 14-kDa protein was absolutely dependent on the second in-phase ATG codon. Efficient biosynthesis of glycoprotein G2 was shown to depend on one or more ATG codons within the preglycoprotein region, but not the first one of the ORF. Synthesis of about one-half of the total glycoprotein G1 was affected by the amino acid changes that eliminated ATG codons, while production of the remainder appeared to be independent of all ATG codons in the preglycoprotein region. These data indicated that the means for glycoprotein G1 biosynthesis was distinct from those of the other three M-segment gene products. The results presented herein suggest that a surprisingly complex expression strategy is employed by the RVFV M segment. Although the full nature of the mechanisms involved in the biogenesis of the four RVFV M-segment proteins remains unclear, it does involve the use of at least two (ATG codons 1 and 2), and likely more, distinct translation start sites within the same ORF to produce its complete complement of gene products. PMID- 2319646 TI - Cap-independent enhancement of translation by a plant potyvirus 5' nontranslated region. AB - The RNA genome of tobacco etch virus (TEV), a plant potyvirus, functions as an mRNA for synthesis of a 346-kilodalton polyprotein that undergoes extensive proteolytic processing. The RNA lacks a normal 5' cap structure at its terminus, which suggests that the mechanism of translational initiation differs from that of a normal cellular mRNA. We have identified a translation-enhancing activity associated with the 144-nucleotide, 5' nontranslated region (NTR) of the TEV genome. When fused to a reporter gene encoding beta-glucuronidase (GUS), the 5' NTR results in an 8- to 21-fold enhancement over a synthetic 5' NTR in a transient-expression assay in protoplasts. A similar effect was observed when the 5' NTR-GUS fusions were expressed in transgenic plants. By using a cell-free translation system, the translation enhancement activity of the TEV 5' NTR was shown to be cap independent, whereas translation of GUS mRNA containing an artificial 5' NTR required the presence of a cap structure. Translation of GUS transcripts containing the TEV 5' NTR was relatively insensitive to the cap analog m7GTP, whereas translation of transcripts containing the artificial 5' NTR was highly sensitive. The 144-nucleotide TEV 5' NTR synthesized in vitro was shown to compete for factors that are required for protein synthesis in the cell free translation reaction mix. Competition was not observed when a transcript representing the initial 81 nucleotides of the TEV 5' NTR was tested. These results support the hypothesis that the TEV 5' NTR promotes translation in a cap independent manner that may involve the binding of proteins and/or ribosomes to internal sites within the NTR. PMID- 2319647 TI - Identification of interferon-resistant subpopulations in several strains of measles virus: positive selection by growth of the virus in brain tissue. AB - Subacute sclerosing panencephalitis (SSPE) is a chronic and usually fatal central nervous system disease caused by a persistent infection with measles virus. The pathogenic mechanisms of the disease are poorly understood, but restricted expression of viral antigens within the infected tissue appears to be involved. We have previously proposed that interferon (IFN) plays a role in the pathogenesis of SSPE by interacting with viral subpopulations that are relatively resistant to IFN-mediated inhibition. Such IFN-resistant viral subpopulations have now been identified in six independent strains of measles virus, two derived from patients with measles and four derived from patients with SSPE. By means of a replicative-plating procedure, these IFN-resistant viruses were found to be heterogeneous with respect to their growth in the presence of high levels of IFN. One viral form replicates fully, with complete destruction of the infected-cell culture, whereas the other form induces a restricted, self-limited form of cytopathic effect, similar to that seen with cell-associated strains of measles virus isolated from SSPE patients. Passage of a virus stock containing both of these viral forms through the central nervous system tissue of newborn hamsters strongly selects for the viral form associated with the self-limiting type of cytopathic effect. The presence of this form of IFN-resistant virus coupled with chronic production of IFN within the central nervous system may account for viral persistence in SSPE patients. PMID- 2319648 TI - Mutagenesis of the conserved 51-nucleotide region of Sindbis virus. AB - We have constructed 25 site-specific mutations in a domain of 51 nucleotides in Sindbis virus that is highly conserved among all alphaviruses sequenced to date. These 51 nucleotides are capable of forming two hairpin structures and are found from nucleotides 155 to 205 in Sindbis virus within the region encoding nsP1. Of the mutations, 21 were silent and did not lead to a change in the amino acid sequence encoded. These silent mutations changed not only the linear sequence but also the stability of the hairpins in most cases. Two double mutants that were constructed led to the replacement of one base pair by another so that the linear sequence was altered but the nature of the hairpins was not. All of the mutants with silent mutations were viable, but 19 of the 21 mutants were severely impaired for growth in both chicken and mosquito cells. Compared with the parental virus, they grew slowly and produced virus at rates of 10(-1) to 10(-4) times the parental rate. Surprisingly, however, the plaques produced by these mutants were indistinguishable from those produced by the parental virus. Two of the silent mutations, found within the first hairpin structure, produced virus at a faster rate than the parental virus. It is clear that the exact sequence of this region is important for some aspect of virus replication. We suggest that one or more proteins, either virus encoded or cellular, bind to the hairpin structures in a sequence-specific fashion in a step that promotes replication of the viral RNA. Of the mutations that resulted in a change of coding, only one of four was viable, suggesting that the amino acid sequence encoded in this domain is essential for virus replication. PMID- 2319649 TI - Cell-type-specific control elements of the lymphotropic papovavirus enhancer. AB - Lymphotropic papovavirus (LPV) exhibits a highly restricted host range, in which only cells of primate B-lymphocyte origin are permissive for infection. Its enhancer element contributes to this tropism, since transcriptional potentiation is confined to cells of the hematopoietic lineage. Nuclear extracts from B and T cells, but not from HeLa cells, contain protein factors that interact specifically with the LPV 63-base-pair enhancer repeat, as demonstrated by DNase I footprinting and gel retardation experiments. Within the repeat three sequence motifs were identified: the core motif, the Pu box, and a novel element named T motif. Functional analysis demonstrated that these motifs as well as some sequences upstream of the repeat contribute to the optimal activity of the enhancer. There are clear differences between the patterns of binding of the B and T lymphocyte nuclear proteins to the enhancer which are also reflected in the transcriptional activity of the enhancer in both cell types. Furthermore, the activity of the LPV enhancer and its interaction with nuclear proteins seem to be regulated during B-cell differentiation. PMID- 2319650 TI - The 22,000-kilodalton protein of respiratory syncytial virus is a major target for Kd-restricted cytotoxic T lymphocytes from mice primed by infection. AB - Recombinant vaccinia viruses containing the 22-kilodalton protein (matrixlike or 22K protein) or phosphoprotein gene from respiratory syncytial virus were constructed. These recombinant viruses expressed proteins which were immunoprecipitated by appropriate respiratory syncytial virus antibodies and comigrated with authentic proteins produced by respiratory syncytial virus infection. The new recombinant viruses (and others previously described containing the attachment glycoprotein, fusion, or nucleoprotein genes of respiratory syncytial virus) were used to infect target cells for cultured polyclonal cytotoxic T lymphocytes generated from the spleens of BALB/c or DBA/2 mice primed by intranasal infection with respiratory syncytial virus. Respiratory syncytial virus-specific cytotoxic T lymphocytes (CTL) showed strong Kd (but not Dd)-restricted recognition of the 22K protein. As previously reported, the fusion protein and nucleoprotein were both seen by CTL, but recognition of these proteins was comparatively weak. There was no detectable recognition of other respiratory syncytial virus proteins tested (including phosphoprotein). 22K protein-specific splenic memory CTL persisted for at least 11 months after infection of BALB/c mice. Priming BALB/c mice with recombinant vaccinia virus containing the 22K protein gene induced respiratory syncytial virus-specific memory CTL at lower levels than that previously reported following infection with a similar recombinant containing the fusion protein gene. These data identify the 22K protein as a major target antigen for respiratory syncytial virus-specific CTL from H-2d mice primed by respiratory syncytial virus infection. PMID- 2319651 TI - Promoter for Sindbis virus RNA-dependent subgenomic RNA transcription. AB - Sindbis virus is a positive-strand RNA enveloped virus, a member of the Alphavirus genus of the Togaviridae family. Two species of mRNA are synthesized in cells infected with Sindbis virus; one, the 49S RNA, is the genomic RNA; the other, the 26S RNA, is a subgenomic RNA that is identical in sequence to the 3' one-third of the genomic RNA. Ou et al. (J.-H. Ou, C. M. Rice, L. Dalgarno, E. G. Strauss, and J. H. Strauss, Proc. Natl. Acad. Sci. USA 79:5235-5239, 1982) identified a highly conserved region 19 nucleotides upstream and 2 nucleotides downstream from the start of the 26S RNA and proposed that in the negative-strand template, these nucleotides compose the promoter for directing the synthesis of the subgenomic RNA. Defective interfering (DI) RNAs of Sindbis virus were used to test this proposal. A 227-nucleotide sequence encompassing 98 nucleotides upstream and 117 nucleotides downstream from the start site of the Sindbis virus subgenomic RNA was inserted into a DI genome. The DI RNA containing the insert was replicated and packaged in the presence of helper virus, and cells infected with these DI particles produced a subgenomic RNA of the size and sequence expected if the promoter was functional. The initiating nucleotide was identical to that used for Sindbis virus subgenomic mRNA synthesis. Deletion analysis showed that the minimal region required to detect transcription of a subgenomic RNA from the negative-strand template of a DI RNA was 18 or 19 nucleotides upstream and 5 nucleotides downstream from the start of the subgenomic RNA. PMID- 2319652 TI - Direct sequencing of the HA gene of influenza (H3N2) virus in original clinical samples reveals sequence identity with mammalian cell-grown virus. AB - When influenza (H3N2) viruses from infected individuals are grown in embryonated chicken eggs, viruses are isolated which differ antigenically and structurally from viruses grown in mammalian Madin-Darby canine kidney (MDCK) cell culture [G.C. Schild, J.S. Oxford, J.C. de Jong, and R.G. Webster, Nature (London) 303:706-709, 1983]. To determine which of these viruses is most representative of virus replicating in the infected individual, a region of the HA gene of virus present in original clinical samples was amplified by using the polymerase chain reaction and sequenced directly. Comparison of 170 amino acid residues of HA1 flanking and containing the receptor-binding site and antigenic sites indicated that over this region, the HA of virus replicating in the infected individual was identical to that of virus after growth in MDCK cells and was distinct from the HA of viruses grown in eggs. Therefore, cultivation of human influenza H3N2 virus in mammalian MDCK cells results in a virus similar to the predominant population of virus found in the infected individual. PMID- 2319653 TI - Structure and orientation of expressed bovine coronavirus hemagglutinin-esterase protein. AB - The sequence of the hemagglutinin-esterase (HE) gene for the Mebus strain of bovine coronavirus was obtained from cDNA clones, and its deduced product is a 47,700-kilodalton apoprotein of 424 amino acids. Expression of the HE protein in vitro in the presence of microsomes revealed N-terminal signal peptide cleavage and C-terminal anchorage but not disulfide-linked dimerization. Dimerization was observed only after expression in vivo, during which HE was also transported to the cell surface. PMID- 2319654 TI - A single element within the hepatitis B virus enhancer binds multiple proteins and responds to multiple stimuli. AB - The hepatitis B virus enhancer can be dissected into multiple functional elements, one of which is the E element. We show here that the E element binds multiple nuclear proteins that are essential for its enhancer activity. These findings, together with the ability of this element to respond to at least two different viral transactivators, suggest that the E element is an enhancer modulator capable of binding different factors and responding to multiple stimuli. PMID- 2319656 TI - As nation grows older, falls become greater source of fear, injury, death. PMID- 2319657 TI - Research focuses not only on where, why, how of falls, but also on preventing them. PMID- 2319655 TI - Molecular cloning of pneumonia virus of mice. AB - cDNA clones representing nine genes of pneumonia virus of mice (PVM) have been generated. The sizes of the corresponding mRNAs and a provisional transcriptional map of the virus genome have been determined. The apparent gene order is very similar to that of respiratory syncytial virus. The sequences adjacent to the 3' termini of the PVM genes were determined and are very similar to those of respiratory syncytial virus. Several PVM gene polypeptide products have been assigned. PMID- 2319658 TI - Federal officials hearing plenty (of opposition) during comment period on new laboratory rules. PMID- 2319659 TI - Orthopedic surgery turns attention to relatively few fractures that fail to heal over time. PMID- 2319660 TI - From the Centers for Disease Control. Update: tuberculosis elimination--United States. PMID- 2319661 TI - From the Centers for Disease Control. Influenza--United States, 1989-1990. PMID- 2319662 TI - Attempting to ensure physician competence. PMID- 2319663 TI - Exercise, fitness, and mortality. PMID- 2319664 TI - Observations on the inverse correlation of TSH with FTI. PMID- 2319665 TI - Arterial-venous differences in plasma concentrations of nicotine after cigarette smoking. PMID- 2319666 TI - Teenage suicide clusters. PMID- 2319667 TI - Human immunodeficiency virus infections in teenagers. Seroprevalence among applicants for US military service. The Walter Reed Retrovirus Research Group. AB - Between October 15, 1985, and March 31, 1989, serum specimens from 1 141 164 teenaged youths (aged less than 20 years) who applied for entry into the US military were tested for antibodies to the human immunodeficiency virus. Overall, 393 teenaged applicants were found to be seropositive (prevalence, 0.34 per 1000). Prevalences varied markedly in different geographic locales: less than 0.1 per 1000 throughout the north-central states, compared with greater than 2 per 1000 in urban counties in Maryland, Texas, New York, and the District of Columbia. Overall, rates among teenaged males (345/991 445; prevalence, 0.35 per 1000) and teenaged females (48/150 013; prevalence, 0.32 per 1000) were comparable. The prevalence among black teenaged applicants (1.06 per 1000) was greater than that among white (0.18 per 1000) or Hispanic (0.31 per 1000) teenaged applicants. Infections with the human immunodeficiency virus are not rare among teenaged Americans. PMID- 2319668 TI - Informing physicians about promising new treatments for severe illnesses. AB - Physicians are increasingly informed of promising new treatments for severe illnesses through unconventional communications such as press releases, press conferences, and direct mailings. These highly publicized announcements disseminate information quickly, often many months before new data are presented at medical meetings or published in peer-reviewed medical journals. Such unconventional communications, however, usually do not provide sufficient detail for physicians to evaluate new studies, answer patients' questions, or make recommendations. We suggest that physicians would be better informed about therapeutic advances through (1) expanded information in unconventional communications, (2) increased availability of information from the Food and Drug Administration, (3) early submission and accelerated review of key medical journal articles, and (4) expanded use of on-line computerized information sources. A commitment to inform physicians better about promising new treatments may help save or prolong the lives of patients with severe illnesses. PMID- 2319669 TI - Declining serum cholesterol levels prior to diagnosis of colon cancer. A time trend, case-control study. AB - We report the results of a 10-year, time-trend, case-control study in which serum cholesterol level was determined at several points in time preceding the diagnosis of colon cancer in a population of individuals who sought general checkups at an ambulatory care screening facility. Each of the 69 patients with colon cancer (32 men and 37 women) was matched with a control patient who was randomly selected. At the time of diagnosis, the patients with colon cancer had significantly lower serum cholesterol values than control patients (5.56 +/- 0.31 mmol/L [SEM] vs 6.47 +/- 0.34 mmol/L). This difference did not vary with sex or Dukes' stage of the cancer. The percent of matched pairs in which the cancer patient had a lower serum cholesterol level increased from 42% at 10 years prior to cancer diagnosis to 77% at diagnosis. The ratio of serum cholesterol at each period to the level at time of diagnosis demonstrated an average decline of 13% during the 10 years prior to diagnosis for case patients vs an average rise of 2% in the same period for control patients. We conclude that individuals in whom colorectal cancer develops share the same level of serum cholesterol as the general population initially, but during the 10 years preceding the cancer demonstrate a decline in serum cholesterol level that is opposite to the rising level seen with age in the general population. PMID- 2319670 TI - Occupational risks for child-care providers and teachers. PMID- 2319671 TI - A piece of my mind. The spouses' programme. PMID- 2319672 TI - An academic nightmare: new policies on student loan deferment. PMID- 2319673 TI - AIDS giving rise to cardiac problems. PMID- 2319674 TI - Next step on road to possible gene therapy expected in June, but many steps remain. PMID- 2319675 TI - International conference gives boost in including omega fatty acids in diet. PMID- 2319676 TI - Heart Association discontinues seal of approval. PMID- 2319677 TI - From the Agency for Health Care Policy and Research. PMID- 2319678 TI - From the Congressional Office of Technology Assessment. PMID- 2319679 TI - From the Centers for Disease Control. Rabies in a Llama--Oklahoma. PMID- 2319680 TI - Fluoride supplementation of the breast-fed infant. PMID- 2319681 TI - Medical malpractice and the tort system. PMID- 2319682 TI - HTLV-I/II infection in women with acute pelvic inflammatory disease. PMID- 2319683 TI - The (internal) dangers of acrylic fingernails. PMID- 2319684 TI - Prescribed use of cholesterol-lowering drugs in the United States, 1978 through 1988. AB - Data from two pharmaceutical marketing research databases, the National Prescription Audit and the National Disease and Therapeutic Index, were used to study trends in outpatient use of cholesterol-lowering drugs in the United States from 1978 through 1988. Retail pharmacies dispensed an estimated 4.4 million prescriptions for cholesterol-lowering drugs in 1978. This declined to 2.6 million in 1983 and increased dramatically to nearly 13 million in 1988. This fivefold increase between 1983 and 1988 was accounted for primarily by the introduction and use of two new drugs, gemfibrozil and lovastatin, and, to a lesser extent, by the increasing use of some older drugs. In 1988, after 1 full year of marketing, lovastatin was the leading cholesterol-lowering drug, followed closely by gemfibrozil; both drugs are currently considered second-line agents. Clofibrate and dextrothyroxine, drugs that ranked first and second in 1978, declined to ranks of sixth and eighth out of eight in 1988. Cholestyramine, gemfibrozil, and lovastatin accounted for about 75% of all lipid-lowering prescriptions in 1988. From 1978 through 1988, an average 54% of individuals using cholesterol-lowering drugs were 60 years of age or older. The 13 million prescriptions for cholesterol-lowering drugs in 1988 represent a maximum estimate of 13 million treated individuals. This number compares with the 60 million Americans with high cholesterol levels who are candidates for dietary advice, and, if cholesterol levels do not improve, for combined diet and drug intervention. PMID- 2319685 TI - The effect of female sex hormones on cancer survival. A register-based study in patients younger than 20 years at diagnosis. AB - The hypothesis that the female survival advantage in many cancers is dependent on sexual maturity was tested in a population-based cohort. Complete follow-up through 1986 was achieved in virtually all 6262 individuals in Sweden who were diagnosed from 1960 through 1984 as having a malignant disease before the age of 20 years. Proportional hazards analysis revealed a 22% lower death rate overall in females than in males. The difference was unrelated to age at diagnosis for tumors arising in the nervous system and the hematopoietic system (lymphomas and leukemias) but strongly dependent on age for sarcomas and, notably, for all remaining cancers--mostly epithelial. Males and females had similar hazard rates for epithelial cancers before the age of 11 years. At ages 11 to 19 years, the rates in females were 55% to 65% lower than in males. One conceivable explanation for these findings is that female sex hormones prevent the establishment of distant metastases in certain malignant diseases. PMID- 2319686 TI - 'Common courtesy' and the elimination of passive smoking. Results of the 1987 National Health Interview Survey. AB - The tobacco industry recommends "common courtesy" as the solution to potential conflicts over smoking in public places and as an alternative to policies that restrict or ban smoking. Specifically, the industry suggests that nonsmokers "mention annoyances in a pleasant and friendly manner" and that smokers ask others, "Do you mind if I smoke?" We analyzed data for 22,000 adults who responded to the 1987 National Health Interview Survey of Cancer Epidemiology and Control to determine if common courtesy is being used in passive-smoking situations. Almost half (47%) of smokers said they light up inside public places without asking if others mind. When someone lights up a cigarette inside a public place, only 4% of nonsmokers ask the person not to smoke despite the fact that most nonsmokers consider secondhand smoke harmful and annoying. We compared these data with similar data collected by the Roper Organization in the 1970s and found that smokers today are less likely to smoke inside public places. However, nonsmokers' actions in response to secondhand smoke have changed very little. These findings show that the common courtesy approach endorsed by the tobacco industry is unlikely, by itself, to eliminate exposure to environmental tobacco smoke. Though no one would oppose the use of common courtesy, we conclude that legislative or administrative mechanisms are the only effective strategies to eliminate passive smoking. PMID- 2319687 TI - The road to euthanasia. PMID- 2319688 TI - A piece of my mind. When to touch. PMID- 2319689 TI - Clinical decision making: from theory to practice. Guidelines for policy statements: the explicit approach. PMID- 2319690 TI - [An analysis of the cellular DNA contents in lung-metastasized stomach cancers]. AB - A study has been conducted of the cellular DNA contents in the primary and metastatic lesions of 30 cases of lung-metastasized stomach cancers, in which each DNA Index (DI) was calculated and analysed comparatively. As a consequence, the rate of the diploid type in the nodular lung metastases was found to be higher than the rate of the others. Further, the DI's of 22 out of 30 (73%) metastatic lymph nodes corresponded with those of the primary lesions. Four lung metastatic lesions out of five differed from their primary lesions, but all five lesions simulated their metastatic lymph nodes. Thus understanding of the properties of the metastatic lymph nodes, rather than their primary lesions, would seen to be helpful in planning the therapy to combat recurrent cancers. PMID- 2319691 TI - [The ornithine decarboxylase activity of the gastric remnant mucosa: the effect of the duodenal juice with bile on the gastric mucosa]. AB - Using male Wister rats, the ornithine decarboxylase (ODC) activity in the fundic mucosa has been determined from the duodenal juice with bile of a reflux model. The activity at 24 hours postoperatively presented a value approximately 18 times higher than the preoperative level. Though this level declined subsequently, it still was approximately two times higher four weeks later. The ODC activity in the corporal mucosa of humans was compared in 25 normal persons, in 21 patients with a gastric adenoma in 29 patients with a gastric cancer, in 20 patients who had undergone a Billroth I operation and in 20 patients who had undergone a Billroth II operation. No differences in ODC activity were observed among those with a gastric adenoma, a gastric cancer, and normal cases but significantly higher values were seen in cases with a remnant stomach, particularly those who had undergone Billroth II reconstructive surgery. Further, this activity tended to be especially high from 5 to 15 years postoperatively in cases with a gastric remnant. PMID- 2319692 TI - [Trends in the incidence of uterine cancer in Nagasaki city, with special reference to previous atomic bomb exposure, 1973-1982]. AB - An epidemiological study has been conducted to elucidate the trend in the incidence of uterine cancer, a with a reference also to previous A-bomb exposure. Studied were 783 cases (345 exposed and 438 nonexposed) of uterine cancer that were handled from 1973 to 1982. The incidence rate of cervical cancer was significantly higher among the population who came into Nagasaki city within two weeks after exposure. A comparison between the incidence rate of '73-'77 and '78 '82 revealed a decreasing trend of cervical cancer and an increasing trend of corpus cancer. The increasing rate of corpus cancer was higher in the younger group of a-bomb survivors (less than 59 years old) than in the other survivors. PMID- 2319694 TI - [Curability of multidisciplinary treatment including combined hyperthermia, radiotherapy and chemotherapy]. AB - Reported are the results in 311 patients who received a multidisciplinary treatment for their cancers, said treatment combining hyperthermia, radiotherapy, and chemtherapy. Of his number, 266 patients were in the advance stage of their disease while another 42 still had localized cancers. According to the criteria of Koyama and Saitoh for evaluating solid tumors that had received chemotherapy, of 298 evaluable patients, 64 showed a complete response (CR), 94 showed a partial response (PR), 89 showed no change (NC), and 57 showed a progressive disease (PD), for an overall response of 53.0% (158 cases). A multidisciplinary treatment combining radiotherapy and hyperthermochemotherapy was used for cases involving localized tumors of the vulva, the skin, the thyroid gland, the prostate gland, the uterus, the rectum, the soft tissue bone, and the ovary, though our treatment regimen could not be continued in cases of tumors involving the stomach, the esophagus, the lung, the mediastinum, the liver, and the pancreas. Our data has shown that a high overall rate of curability was achieved in cases involving the stomach, the bladder, the blood, the skin, the head, and neck, and the esophagus. PMID- 2319693 TI - [Computed tomography for the assessment of pelvic lymph node metastasis in cases of uterine cervical carcinoma]. AB - Seventy-six patients with cervical cancers underwent preoperative abdominopelvic computed tomography before a pelvic lymphadenectomy to evaluate the efficacy of computed tomography in assessing pelvic lymph node metastases. The sensitivity and the specificity of computed tomography for detecting pelvic lymph node metastases were judged to be 70.6 and 89.8%, respectively. In 54 patients in stage Ib or IIa of the disease, the sensitivity and specificity were 85.7 and 91.5%, respectively. Although inaccuracies could be caused by normal-sized metastasized lymph nodes and by enlarged lymph nodes with reactive hyperplasia, computed tomography was found to be a useful method of detecting a pelvic lymph node metastasis. PMID- 2319696 TI - Epidemiologic approaches to multiple primary cancer: critical review from the standpoints of validity and efficiency. AB - Epidemiologic approaches to multiple primary cancer (MPC) have been reviewed from the standpoints of validity of study design and statistical efficiency. It was shown that the expected number of MPC is often over- or underestimated when the person-year method is used in calculation. This so-called detection bias becomes stronger the poorer the prognosis of patients with their first cancer, and the longer the duration of the preclinical state of their second cancer. The bias is also affected by the probability of detecting the second cancer at the time as the first. An alternative method has been proposed, in which the prevalence rate of preclinical cancer is evaluated. The efficiency with which the increased frequency of second cancer is detected is affected not only by the risk ratio for individuals at high risk to those at low risk but also by the proportion of high risk individuals in the population. PMID- 2319695 TI - [A case of the Stewart-Treves syndrome (post-mastectomy angiosarcoma) with special reference to a radiological study]. AB - Reported is the case of a 54-year-old female manifesting the Stewart-Treves syndrome (a postmastectomy angiosarcoma.) The patient had developed an angiosarcoma in her lymphoedematous right shoulder and lower neck develop ten years after a radical mastectomy for a papillo-tubular adenocarcinoma of the right mammary gland. Radiologically, a well-enhanced tumor was revealed by computed tomography, which angiographically had more stains and tumor vessels than usual for a mammary carcinoma and less than usually seen in a cavernous hemangioma. Histologically, this tumor showed less of a luminal differentiation than a conventional angiosarcoma and resembled a fibrosarcoma. Computed tomography and angiography were found useful in achieving a diagnosis and the subsequent therapy for this Stewart-Treves syndrome. PMID- 2319697 TI - Long-term survival after brain metastases from tracheal carcinoma. AB - A case of prolonged survival after radiotherapy for primary tracheal squamous cell carcinoma and the subsequent brain metastases is reported. The patient is alive and well without any sign of relapse, approximately six years after the onset of brain metastases from tracheal carcinoma. Radiotherapy proved useful in the treatment of both the primary tracheal carcinoma and the brain metastases. PMID- 2319698 TI - Symposium on fundamental and clinical research in liver cancer. PMID- 2319699 TI - Summary of National Nutrition Survey 1980-1984 by prefecture. PMID- 2319700 TI - Geographical distribution of biliary tract cancer in Niigata prefecture. AB - We reviewed 1074 surgically treated patients with biliary tract cancer (gallbladder 564, bile duct 510) in Niigata prefecture in the five-year period from 1982 to 1986. Analyses of regional distributions revealed the incidence of gallbladder cancer to be highest in the Ka-etsu district (northern part of prefecture) and lowest in the Jo-etsu district (south-western part of prefecture). The incidence of bile duct cancer was highest in the district controlled by the most northern public health center and lowest in Chu-etsu district (central part of prefecture). The incidences of gallbladder and bile duct cancers showed regional variations within the prefecture, localization being more pronounced for gallbladder cancer. PMID- 2319701 TI - Maternal factors of testicular cancer: a case-control study in Japan. AB - A case-control study was undertaken in Japan to clarify maternal or prenatal factors associated with testicular cancer. Information was obtained from 37 mothers of testicular cancer patients, recruited from the discharge records of nine hospitals in Hokkaido, the northern island of Japan. Thirty-seven mothers forming a control group were then surveyed at five public health centers. Each control was selected by individually matching the sex and birth year to a testicular cancer case. Univariate analysis revealed that there were no statistically significant differences in the variables surveyed. Multivariate logistic regression analysis, however, showed that case mothers had significantly fewer live-births than control mothers when the following four variables were adjusted (adjusted relative risk per live-birth = 0.43, P = 0.025): age at indexed birth, duration of breast-feeding for indexed child, birth order, experience of induced abortion. PMID- 2319702 TI - DNA ploidy patterns in gallbladder adenocarcinoma. AB - DNA ploidy patterns in gallbladder carcinoma were examined by flow cytometry using paraffin-embedded tissues. The incidence of DNA aneuploidy was 46.3% and of a diploid pattern, 53.7%. No relation could be observed between DNA ploidy pattern and histological type. There was a tendency for the incidence of diploid patterns in early carcinomas to be higher than that of aneuploidy patterns, but there was no significant difference. No obvious correlation could be demonstrated between DNA ploidy pattern and prognosis. Gallbladder carcinomas were divided into metaplastic and non-metaplastic types based on the presence or absence of metaplastic changes, in accordance with our classification. The relation between DNA ploidy pattern and tumor type was examined, but none was observed. In the present study, no correlation could be observed between DNA ploidy pattern and clinicopathologic findings in gallbladder carcinoma. PMID- 2319703 TI - Carcinosarcoma of the esophagus: a twenty-case study. AB - The present report reviews results from 20 carcinosarcoma patients, and compares them with 773 cases of squamous cell carcinoma of the esophagus treated surgically at the National Cancer Center Hospital from 1971 to 1988. Although there were no significant differences in age, sex, symptoms or location between the two groups, the carcinosarcoma group had morphological characteristics as follows. (1) Seventy-five percent of the carcinosarcomas were of the elevated type. (2) The tumor was large. (3) The depth of invasion was limited to the esophageal wall in 80% of the carcinosarcomas. The rate of lymph node metastasis was almost the same, at greater than 65%, in both groups. Moreover, lymph node metastasis occurred at various stages, of the depth of invasion in the carcinosarcoma group. The curative resection rate was higher for carcinosarcoma (80%) than for squamous cell carcinoma (46.5%). There was no significant difference in recurrence rate between them. Compared with the high frequency of lymph node recurrence in the squamous cell carcinoma group, the recurrence due to hematogenous metastasis was more frequent in the carcinosarcoma group. Although the three-year survival rate was higher for carcinosarcoma (62.8%) than for squamous cell carcinoma (28.1%), there was no significant difference in the five year survival rate between them (26.7 vs. 22.4%). In conclusion, radical esophagectomy with lymph node dissection is a necessary therapy for carcinosarcoma, and careful follow-up, paying special attention to hematogenous metastasis, is required. PMID- 2319704 TI - [Significance of extreme values of biochemical tests in patients]. PMID- 2319705 TI - [Monitoring of therapeutic courses of acute leukemia by application of mathematical models]. PMID- 2319706 TI - [Computed analysis of electrocardiogram; its algorithm and practice]. PMID- 2319707 TI - [Methods for information system in laboratory medicine--present and future]. PMID- 2319708 TI - [Theoretical study on laboratory diagnosis; expression of data summary]. PMID- 2319709 TI - [Clinical laboratory use and medical decision making]. PMID- 2319710 TI - [Detection of physiological abnormality through the practice of quality control]. PMID- 2319711 TI - [Monitoring of patients laboratory data]. PMID- 2319712 TI - [Cryosurgical treatment of atrial tachyarrhythmia with atrial flutter]. AB - Two cases of atrial tachyarrhythmias with atrial flutter requiring cryosurgical treatment are reported. In two cases, preoperative electrophysiological studies revealed supraventricular reentrant tachyarrhythmias during atrial flutter and showed enhanced conduction through the AV node that conducted atrial impulses rapidly to the ventricle. Based on intraoperative endocardial mapping, the earliest excitation site was localized along the AV node and His bundle during supraventricular tachyarrhythmias in one case. The cryosurgical treatment was administered at Koch's triangles and in one case additionally at coronary sinus. After the operation, supraventricular tachyarrhythmias were not inducible and no clinical recurrences have occurred. Normal atrioventricular conduction was preserved in two cases. We concluded that cryosurgical treatment is useful for the treatment of the atrial tachyarrhythmias. PMID- 2319713 TI - [A case of extraskeletal Ewing's sarcoma of the chest wall]. AB - A case of extraskeletal Ewing's sarcoma arising in the chest wall of a 15-year old male is reported in this paper. His complaint was chest and back pain. Physical examination and laboratory data disclosed no abnormality. Radiographs and computed tomography revealed chest wall tumor, and resection of the tumor with a portion of the eighth rib was performed. Histologically, there was no involvement of the rib at all. The tumor tissue was composed of solidly packed tumor cells which were uniform in size and shape. Individual tumor cells were small, round-shaped, and had scanty, ill-defined cytoplasm. The diastase digested, PAS positive material was found in the cytoplasm. NSE (neuron specific enolase) was positive, but EMA (epithelial membrane antigen) LCA (leucocyte common antigen), and keratin were negative. With these results, we got a diagnosis of extraskeletal Ewing's sarcoma. Combination chemotherapy with vincristine, cyclophosphamide, adriamycin, actinomycin D was administered after operation, and there is no evidence of recurrence after 12 months of follow-up. PMID- 2319714 TI - [A case report of implantation of the Greenfield vena cava filter for recurrent pulmonary embolism]. AB - A 68-year-old woman with recurrent pulmonary embolism due to deep vein thrombosis underwent implantation of a Greenfield vena cava filter. She has no signs of recurrence and complications for 15 months postoperatively. We recommend this filter for the properly selected patients. PMID- 2319715 TI - [Three cases of left atrial myxoma]. AB - Three cases of left atrial myxoma are presented. All of them were diagnosed by echocardiography, computed tomography and cardiovascular angiography. At operation, origin of the tumors were found to arise from the vicinity of the fossa ovalis in two cases and the lower atrial septum in the other. Three different operative maneuvers were used in these three cases. In the first case, the left atrium was incised and the tumor was removed submucosally. In the second case, the left and right atrium were incised and the tumor was removed with atrial septum. In the third case, only the right atrium was incised and the tumor was removed with atrial septum. In comparison of these three different maneuvers, we conclude that the second case was most appreciable, because the operator could see whole sight of the left atrial cavity and whole contour of the tumor and remove the tumor completely without destruction. All these patients have done well for periods of follow-up ranging from 10 to 37 months. PMID- 2319716 TI - [Primary lung cancer in young adults]. AB - Despite a recent trend of rapid increase in the incidence of lung cancer in Japan, lung cancer has been detected rarely among young patients. The findings in 15 patients under 40 years of age who underwent surgery for primary lung cancer at Cancer Institute Hospital (C.I.H.) are presented. Fourteen were located in the region of the periphery. Ten of the 14 peripheral lesions were adenocarcinoma. The chances of cure or even long survival are very small. The case report presents a case with lung cancer in a 22-year-old woman who was the youngest in C.I.H. On histological examination, the excised tumor proved to be moderately differentiated adenocarcinoma. PMID- 2319717 TI - [Resected cases of middle lobe primary cancer]. AB - Of 200 lung cancer lesions resected in our hospital, there were 15 cases (7.5%) with middle lobe origin. The histological types were adenocarcinoma in 13 patients (4 patients with alveolar cell carcinoma), squamous cell carcinoma in one and large cell carcinoma in one. These patients were classified into two groups according to the type of operation they received and each group was evaluated. Group I (resection of the middle lobe) included 8 patients. Each one of Stage IIIB and Stage IV received the operation to improve their symptoms. The six patients of Stage I received only middle lobectomy as absolute curable cases. Group II (resection of the middle and lower lobes) included 7 patients, who had preoperative diagnosis of stage III. Two of them were postoperatively found to be cases of Stage I and Stage II. Although it was still short-term, the follow-up evaluation proved that these patients survived without local recurrence and distant metastasis, except for two with pleural dissemination and one with cerebral metastasis, who had received lobectomy as palliative operation. No difference was observed between the two groups receiving different types of operation. PMID- 2319718 TI - [Reoperation of tetralogy of Fallot long after correction with aortic homograft: a case report]. AB - Late results in the surgery for congenital heart disease repaired with external conduit have not yet been fully elucidated. We experienced a reoperation of tetralogy of Fallot (TF) that was previously repaired with an aortic homograft pretreated with beta-propiolactone for the reconstruction of right ventricular outflow tract. Ten years after correction of TF, right ventricular failure developed due to the regurgitation of tricuspid valve. At reoperation tricuspid annuloplasty was performed, and the valve of aortic homograft was also replaced with xenograft because of its uncertain durability. However, the resected valve had pliability with least degenerative change macroscopically. The postoperative course was smooth. The case was a rare one of late reoperation of TF due to the tricuspid valve regurgitation, and the case also indicated unexpected long durability of the valve cusp of the aortic homograft. PMID- 2319720 TI - [VAD: ventricular assist device]. PMID- 2319719 TI - [Improvement of heart failure after intracardiac operation for tetralogy of Fallot by transcatheter embolization of major aortopulmonary collateral arteries]. AB - A two-year-and-ten-month-old female with tetralogy of Fallot with major aortopulmonary collateral arteries (MAPCAs) developed a persistent heart failure after an intracardiac repair. Angiograms revealed four MAPCAs originating from the upper portion of the descending thoracic aorta and draining into the left pulmonary artery, one MAPCA from the inferior phrenic artery into bilateral pulmonary arteries, and remaining one from the left subclavian artery into left pulmonary artery. Three of these MAPCAs were occluded by transcatheter embolization by the use of the steal coil. The heart failure was improved dramatically by this treatment. PMID- 2319721 TI - [A case of supravalvular aortic stenosis treated by Doty's operation]. AB - A 11-year-old boy with supravalvular aortic stenosis was treated by extended aortoplasty (Doty's operation) with excellent results. The extended aortoplasty provided satisfactory relief of aortic stenosis and improved function of the aortic valve. PMID- 2319722 TI - [Two cases of wedge pneumonectomy in primary lung cancer involved into carina]. AB - Right wedge pneumonectomy was performed on two cases of primary lung cancer involved into carina. A 59-year-old male involved with primary lung cancer was found with bloody sputum. Preoperative data confirmed as the superficial spread type of squamous cell carcinoma in carinal lesion and tumor was resectable with wedge pneumonectomy. In the second case, abnormal shadow was pointed out on chest X-ray film of a 61-year-old male patient. Preoperative examination defined as primary lung cancer of rt-S6 with subcarinal lymph node metastasis. The operation indicated wedge pneumonectomy with patch plasty using the wall of right main bronchus. Although wedge pneumonectomy is not common compared to sleeve pneumonectomy, if available this procedure is technically easier and post operative management may be more successful. Wedge pneumonectomy limits resectable area, because the continuation of tracheo-bronchial wall must be remained in part. Therefore, the indication of this procedure for surgical treatment of lung cancer is limited. However, when this procedure indicates to selected case with limited lesion of carina, this may be an useful procedure as surgical treatment of primary lung cancer. PMID- 2319723 TI - [Treatment of invasive thymoma with myasthenia gravis: a case report responsive to azathioprine and methylprednisolone]. AB - The treatment of invasive thymomas associated with autoimmune diseases, such as myasthenia gravis (MG) and pure red cell aplasia, has not been established. In this paper, we report a 37-year-old patient with post thymectomy myasthenia gravis, who underwent subtotal resection of invasive thymoma with residual lesions of intrathoracic implants. He was treated with azathioprine (AZP) and methylprednisolone (MP). During two months from the start of this therapy, the clinical symptom was improved apparently and the recurrent tumor was reduced. Lasting 18 months of the treatment, he had to stop it because of the renal failure, but now he has no sign of the recurrence. Further studies with this combined regiments are warranted in the treatment of the invasive thymomas associated with autoimmune disease. PMID- 2319724 TI - [A case of mediastinal neurinoma originating from right intrathoracic vagal nerve]. AB - A 34-year-old woman was admitted with an abnormal shadow on a chest X-ray film. Under a preoperative diagnosis of benign bronchogenic cyst, operation was carried out and the tumor was found to be originating from the right main vagal nerve in the mid-superior mediastinum. The vagal nerve was transected to remove the tumor. Pathological diagnosis was a neurinoma. Postoperative complication was chylothorax which was successfully treated with thoracic drainage and intravenous hyperalimentation. PMID- 2319725 TI - [A case report of lung cancer with chest wall invasion arising from a bulla wall]. AB - A 45-year-old man with a history of pulmonary bullae complained of back pain and chest pain while playing golf. His plain chest X-ray film revealed pulmonary bullae and an 8 cm tumorous mass. Although bronchoscopic biopsy was unsuccessful, adenocarcinoma was confirmed by transcutaneous lung biopsy. Because chest wall invasion was found by CT scanning, right upper lobectomy with chest wall resection and dissection of hilar and mediastinal lymph nodes was performed (p T3N0M0, stage IIIA, relative curative resection). The postoperative course was uneventful and no sign of recurrence is evident eight months later. It was strongly suggested by histopathological study that the chest wall invasion of poorly differentiated adenocarcinoma arose from the bulla wall. Formerly, only two non-curatively resected cases with chest wall invasion of lung cancer arising from a bulla have been reported in Japanese literature. PMID- 2319726 TI - [A case of idiopathic fibrous mediastinitis with superior vena caval obstruction]. AB - Uncommon case of superior vena caval obstruction secondary due to idiopathic fibrous mediastinitis was reported. A 38-year-old female was admitted in our hospital with the complaint of dyspnea and facial edema. Venography revealed occlusion of vena cava. Venous pressure showed 30 cmH2O in the external carotid vein. Mediastinal computed tomogram revealed no tumor but calcification in the anterior mediastinal fatty tissue. Therefore, with a 12 cm EPTFE, left brachiocephalic vein-right atrium bypass operation was performed. Facial edema was disappeared dramatically in early postoperative stage. She is uneventful 20 months after the operation. PMID- 2319727 TI - [A case of two-chambered right ventricle complicating severe cyanosis due to tricuspid regurgitation and patent foramen ovale]. AB - A 63-year-old female of two-chambered right ventricle (TCRV) associated with tricuspid regurgitation (TR), patent foramen ovale (PFO) and small ventricular septal defect (VSD) underwent corrective surgery successfully. She suffered severe heart failure and cyanosis with 47.7% of right-to-left shunt through PFO. The VSD was so small that no significant shunt was shown in catheterization data. Operative findings suggested that TR was caused by elongation of the chorda as a consequence of long-term pressure load of right ventricular inflow chamber. Among reported cases of TCRV, the present case is the oldest one who underwent corrective surgery successfully. PMID- 2319728 TI - The right thing--we hope. PMID- 2319729 TI - Deficient benzbromarone elimination: a familial disorder? PMID- 2319730 TI - [The importance of Vitamin B1, B6, B12 in the treatment of pain. New pharmacologic and clinical findings. Wiesbaden, 26 May 1989. Proceedings]. PMID- 2319731 TI - B-vitamins enhance afferent inhibitory controls of nociceptive neurons in the rat spinal cord. AB - Afferent inhibition of spinal dorsal horn neuronal responses to noxious skin heating was induced by transcutaneous electrical nerve stimulation in pentobarbital-anesthetized rats. Pretreatment with B vitamins significantly enhanced this afferent inhibition, possibly due to an increase in the synthesis rate of inhibitory neurotransmitters in central neurones. PMID- 2319732 TI - [Modification of degenerative and regenerative processes in peripheral nerves by treatment with B vitamins]. AB - Degenerative and regenerative changes in the saphenous nerve of the rabbit following systemic treatment with either a combination of the vitamins B1, B6 and B12 or physiological saline solution were investigated. Cold lesion of the nerve (-196 degrees C), which led to an optimal axonotmesis, was used to cause a secondary degeneration. The nerves were removed and investigated by light and electron microscopy after 4, 10 and 21 days. Morphological results show that the number of regenerating axons is higher and that of degenerating axons lower in the group treated with the given doses of vitamins than in the comparable control group. An explanation of the underlying metabolic processes is as yet not possible. Further investigations considering the contribution of the individual vitamins to the enhancement of degenerative and regenerative processes are necessary. Clinical indications of neurotoxicity due to the dose levels used here were not observed. PMID- 2319733 TI - Lipolytic enzymes of the human pancreas. III. Auxiliary function of lipase in the cholesterol-esterase-dependent oral test on exocrine pancreatic output. AB - In the oral exocrine pancreatic function test using fluorescein dilaurate, this synthetic substrate attaches primarily to the triglyceride surfaces of the neutral lipids administered as part of the breakfast: these fluorescein dilaurate molecules cannot be attacked by cholesterol esterase. In the course of triglyceride saponification by lipase and colipase, however, the fluorescein dilaurate is liberated and hydrolyzed by cholesterol esterase. The pancreatic function test, therefore, measures the lipolytic activities not merely of cholesterol esterase, but indirectly of lipase, as well. PMID- 2319735 TI - [Effect of diabetes-psychosomatic group education on metabolic control and coping with disease by insulin-dependent diabetic patients]. AB - Even though cognitive education programs are essential for the treatment of diabetics, long term efficacy often seems to be poor. Problems of coping with illness could be the reason for a lack of transfer of knowledge into daily practice. Small discussion groups with the aim of modifying attitudes towards illness might be a good possibility to face this problem. 54 IDDM, HbA1 10.7 +/- 2.3% (median +/- SD) absolved our 5-day education program for outpatients, in which daily group sessions (90 min), supervised by a group-therapist, were integrated. Follow-up sessions took place after 1, 4 and 8 months. The efficacy was measured by HbA1 and different questionnaires on diabetologic knowledge, life satisfaction (FLZ) and complaints (BL). 4 months after the education program HbA1 had decreased to 9.0 (median +/- SD) and remained stable within small range during the rest of the study-period. Diabetologic knowledge increased from 70% (median +/- SD) to 87% (median +/- SD) 1 month after the education and remained stable during the rest of the study-period. Complaints decreased within one month from a level above average somatic illness to the normal level for healthy subjects. However, in regard to their life satisfaction our patients were significantly less satisfied concerning their health, whereas family life and friendship were declared to be more satisfying (after 8 months). We believe that more intensive communication in the family (encouraged by the group-therapy) and parallel more critical attitudes towards illness lead to this results. As basic elements for long term modification of illness behaviour these emotional aspects seem to be essential. PMID- 2319734 TI - Severe type III hyperlipoproteinemia in two patients maintained on chronic hemodialysis. AB - Two patients with severe hyperlipidemia receiving long-term hemodialysis were classified as type III hyperlipoproteinemic subjects. They are homozygous for apolipoprotein E2 and have an elevated VLDL-cholesterol/plasma-triglyceride ratio. The dyslipoproteinemia was severely aggravated by the renal failure, but careful treatment with bezafibrate was able to effectively lower elevated serum lipids. Accurate diagnosis of lipid abnormalities in patients with chronic renal failure seems to be necessary to plan appropriate therapeutic interventions and to lower the risk for accelerated atherosclerosis. PMID- 2319736 TI - [Colonic neoplasms and skin fibromas: common determinants and their significance]. AB - To find common factors for colonic-neoplasias and skin-tags, 157 inpatients, who consecutively had a coloscopy because of intestinal complaints, were intensively examined dermatologically. Regression-analyses showed that the number of colonic polyps were age- (p = 3 x 10(-8)) and sex-dependent (1.9 x 10(-2)) and skin-tags had no influence on the number of colonic polyps. The size of colonic polyps also showed a clear age dependency (p = 3 x 10(-8)). The number of skin-tags were dependent on weight (p = 9 x 10(-3)) and age (p = 1.3 x 10(-2)), its size on the interaction of sex and triglyceride-levels (p = 3 x 10(-8)). Discriminant analyses identified the following factors as important: age and triglyceride concentration to recognize a patient with colonic polyps; age, positive Haemoccult-test and number of skin-tags to recognize a patient with tubulovillous adenomas or colonic carcinomas. The essential common factor of colonic polyps and skin-tags was the age. For the recognition of a patient with colonic polyps the age was the most essential factor, skin-tags, on the contrary, were unimportant. The association between colonic polyps and skin-tags therefore was merely an effect of age. PMID- 2319737 TI - [AIDS-related complex: a superfluous concept?]. AB - The clinical value of different classification systems of HIV-infection has been examined in a cohort of 99 HIV-infected individuals. AIDS-related complex (ARC), Walter-Reed (WR) stage 5 and Centers for Disease Control (CDC) group IV without AIDS cases were equally capable of identifying patients with bad prognosis: Out of 12 patients progressing to AIDS, 9 WR 5, 7 CDC IV and 7 ARC. Prognostic parameters (Erythrocyte sedimentation rate, Haemoglobin, Leucocytes, CD4 lymphocytes and Beta 2-Microglobulin) did not differ in the three groups. However, there were great differences in the frequency of patients infected by homosexual contacts and of intravenous drug-abusers. Drug-abusers were more often seen in the ARC-group, whereas there was a slight dominance of homosexuals in the WR 5-group (and a marked preponderance in the AIDS-group). Using 3 different ARC definitions we found an ARC-frequency of 10%, 24% and 41% in our cohort. Thus the great variability of the ARC-concept could be demonstrated. In conclusion we believe that for the purpose of clinical documentation and studies the ARC concept is unnecessary. Further studies have to evaluate other classification systems (Walter-Reed, CDC) or to establish new ones. PMID- 2319738 TI - Autoimmune hemolytic anemia in Gaucher's disease. AB - A 23-year-old Ashkenazi woman with Gaucher's disease developed Coombs-positive warm-type autoimmune hemolytic anemia. Treatment with high-dose steroids resulted in complete remission within 2 weeks. Study of an additional 72 patients with Gaucher's disease revealed another case of Coombs-positive warm-type autoimmune hemolytic anemia; other autoimmune disorders were found in 17 of these patients. The possible association of Coombs-positive hemolytic anemia and Gaucher's disease is discussed. PMID- 2319739 TI - [Plasma and urine catecholamines in a 7-day survival of parathion poisoning]. AB - During the intensive medical treatment of a finally fatal parathion poisoning (survival time 7 days) with shock symptoms (lung and kidney) the kinetic profiles of both plasma and urinary catecholamines were taken up. In addition the parathion concentrations of the same plasma samples were measured. There could have been found plasma catecholamine profiles exhibiting peak concentrations in the initial phase, followed by a period of 4 days without any detectable plasma epinephrine and finally an extreme elevation of both catecholamines in the last period before death. The excretion patterns confirmed the plasma results. Imaginable pathophysiological mechanisms in consideration of the shock induced renal insufficiency are discussed. The question is raised whether the kinetics of plasma catecholamines may be a possible marker for the prognosis of organophosphate poisoning. PMID- 2319741 TI - [Survey report on nursing education, 1989]. PMID- 2319740 TI - Health policy: barriers and means of achieving health for all by the year 2000. PMID- 2319742 TI - [Self-love and self-esteem of counselors]. PMID- 2319743 TI - [Avoiding burn-out]. PMID- 2319744 TI - [Chronobiology and shift work: current issues and trends]. PMID- 2319745 TI - [A case study of nursing care in Buerger's disease]. PMID- 2319746 TI - [A study on the nurse's response for the clinical application of nursing diagnosis]. AB - Although the usefulness and importance of clinical application of nursing diagnosis are well recognized by the academic circle, it is not yet generally practiced. In order to provide data for establishing a policy for clinical nursing diagnosis; a study was made at a seminar, sponsored by the Department of nursing, Severance Hospital, with participation of 190 nurses from 33 hospitals. The objective of the study was to find out: 1) if the nurses agree with the academic community in recognizing the benefits and problems of clinical application of nursing diagnosis; 2) how the nurses evaluate their ability to carry out nursing diagnosis; and 3) if educational programs would help enhance ability of nursing diagnosis among nurses. The summary of findings by the study is as follows: 1. While all nurses responded positively on the question of benefits improving science and quality of nursing, thus elevating credibility and position of nurses, some expressed concern on the practicality of the system in setting up nursing objectiveness, confirming the nursing problems and utilizing patient information. For the 20 questions and the scale of 1-5, the lowest average score was 3.223 and the highest 4.066. 2. The study attempted to find out the opinion of the nurses on the problems that would make difficult to adopt the nursing diagnosis in clinics. The result of the study indicates the nurses believe the major problems are the fact that the subject of nursing diagnosis are not well defined and that the form sheets do not match with the ones that are currently being used. However, comparing it with the result of the previous study on the same question (inadequate manpower and insufficient time allocated for the job were two major problems pointed out then). It can be said that the opinion of the nurses studied this time was much more positive and it suggests that they believe the system can be adopted without increasing manpower and only by giving additional training and by adjusting the format of nursing record sheets. It suggests that the future for adopting a clinical nursing diagnosis is very bright. 3. As the most urgent problem to be solved for adopting clinical nursing diagnosis, 38. 5% responded that it was "education of nurses", and 34.2% responded that it was "staffing adequate number of nurses". 4. For the 10 questions asked for self-evaluation of ability to adopt the system, with the scale of 1-5, average score was lower than 3.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2319747 TI - Nursing--a new tomorrow. PMID- 2319748 TI - [Study on the role conflict and professional attitude of health center nurses]. AB - The purpose of this study was to identify role conflict and professional attitude of Health Center nurses for health nursing administration. The data were obtained from 151 nurses of 7 Health Centers in S from July 15 to July 22 1989 using the questionnaires which consisted of 2 scales of role conflict and professional attitude. The data were analyzed by percentage, mean, t-test, ANOVA and Cronbach's alpha reliability test. The results were as follows. 1) Institutional factor had the highest mean score for the degree of role conflict. The relationship between the degree of role conflict and general characteristics was found to be statistically significant for duty position. (F = 2.61, p less than .05). 2) Professional educational level had the highest mean score for the professional attitude. The relationship between professional attitude and general characteristics was found to be statistically significant for educational background. (F = 4.91, p less than .001). PMID- 2319749 TI - Education for blood donation as an avenue for school and community cooperation. PMID- 2319750 TI - Doubling: enhancing the role play technique in schools. PMID- 2319751 TI - Munchausen syndrome by proxy. PMID- 2319752 TI - Condom vending machines in Canada's secondary schools. PMID- 2319753 TI - Providing medical services through school-based health programs. Council on Scientific Affairs. AB - Resolution 162, which was adopted at the 1987 Annual Meeting by the Board of Trustees, called on the American Medical Association to study the efficacy of school-based health clinics. Recent data show that a significant number of school aged youth are in need of an adequate source of health care. School-based health programs constitute a promising avenue for providing health services to adolescents, particularly in medically underserved areas. Although there are insufficient data to support universal establishment of school-based health programs, small-scale studies suggest that such programs are a viable means to increase access to health care for youth. PMID- 2319755 TI - Recommendations for obtaining cooperation to conduct school-based research. AB - Recommendations for obtaining school cooperation to conduct school-based research are offered. Step-by-step protocols are outlined to assist prospective researchers in their quest to gain access to the school environment. The principle reason for adhering to these recommendations is to ensure research that is methodical, thorough, and scrupulous so children will benefit from resultant educational programming. PMID- 2319754 TI - Are health educators being prepared to provide HIV/AIDS education?: A survey of selected health education professional preparation programs. AB - Health education professional preparation programs were surveyed to determine the extent of HIV/AIDS education health educators are receiving. The survey also addressed content areas, skills being developed or enhanced, areas of deficiency in preparation programs, and areas in which national professional associations may assist in the preparation of AIDS educators. One hundred eight-three surveys were mailed; 114 (68%) were completed and returned. Twenty-one institutions reported planning a separate course on HIV/AIDS. Most were designing general service courses to reach a broad cross-section of students. Twenty-five institutions (23.8%) reported previously offering or currently offering a specific course on AIDS. One hundred two (89.5%) respondents reported HIV/AIDS warranted the attention and funding it had received. Thirty-seven (35.2%) respondents reported AIDS education was of sufficient importance to influence hiring of faculty members in their departments. Survey findings demonstrate that current AIDS education courses targeted to the general student population may not be adequate in meeting the professional preparation needs of health educators charged to provide AIDS education. PMID- 2319757 TI - Simple computer controlled goniophotometer for the measurement of early stage changes in biodegradable polymers. AB - Biodegradable polymers exhibit major surface changes that cannot be measured by gravimetric methods. This paper describes a simple, inexpensive system that can accurately record these surface changes. It is based on a laser light source and a scanning photodiode controlled by microcomputer. PMID- 2319756 TI - Heart healthy cook-offs in home economics classes: an evaluation with junior high school students. AB - The Pawtucket Heart Health program works closely with the 23 parochial and public schools in Pawtucket, R.I., to educate students and teachers about heart health promotion. As part of that partnership, the PHHP developed a program to teach junior high school home economics students about nutrition, food purchasing techniques, and heart healthy cooking methods. In this Heart Healthy Cook-off program, the PHHP distributes recipe guidelines to home economics teachers who instruct students in recipe modification, food preparation, and presentation. Students choose recipes and make heart healthy substitutions to lower fat and sodium content. Recipes are analyzed for nutrient content by the PHHP and returned to the students with suggestions for lowering fat and sodium if necessary. Final recipes are judged for heart healthiness by a nutritionist and for taste by a panel of judges. Prizes are awarded to students with winning recipes. Before and after the Cook-offs, classes host a blood cholesterol SCORE (screening, counseling, and referral event) where students learn about their blood cholesterol level and its relationship to dietary intake. In 1988-1989, 105 junior high school students participated in the Cook-off/SCORE program. Forty percent had elevated blood cholesterol levels of 170 mg/dl or above. A statistically significant decrease in blood cholesterol levels was observed during a 12-week time period. The Cook-off is a fun, effective program for teaching secondary school students about heart healthy eating habits. PMID- 2319758 TI - Locally optimum run-length compression of CT images without restriction on the pixel value. AB - Previously reported locally optimum run-length compression of CT images is only applicable to 12 bit images. In order to extend this method to images whose pixel values may vary from 8 bits per pixel to 16 bits per pixel, single byte coding is suggested. A search method is also suggested to make a reasonable determination of the length of non-compressible pixels. Experiments have shown that single byte coding is successful, giving compressed results which are comparable with previously reported results. PMID- 2319759 TI - Improvement in the locally optimum run-length compression of CT images. AB - In the locally optimum run-length compression of X-ray CT images, differential entropy is selected as the criterion for compression. The reported compressed results for 12 bit CT images are 8-9 bits per pixel, which are far from the differential entropies of the boundaries of the compression, from 5.5 to 6 bits per pixel. Our analysis shows that the compression strategy is defective and this is one reason why the compression cannot reach the boundary. Significant improvement has been achieved and the results challenge the selection of differential entropy as a 'theoretical bench mark' for compression. PMID- 2319760 TI - Numerical flow studies in human carotid artery bifurcations: basic discussion of the geometric factor in atherogenesis. AB - In this study fluid dynamic variables are analysed numerically in different human carotid artery bifurcation models in order to clarify the geometric factor in carotid bifurcation atherogenesis. The geometric variations describe healthy human carotid bifurcation anatomy and concern the shape of the carotid sinus and the angle between the branches. The flow conditions remain unchanged. The governing Navier--Stokes equations describing incompressible, pulsatile, three dimensional viscous flow are approximated using a pressure correction finite element procedure which has been developed for time-consuming, three-dimensional, time-dependent viscous flow problems. The study concentrates on flow velocity, on detailed analysis of flow separation and flow recirculation, and on wall shear stress distribution. The results show that the extension and the location of the recirculation zone in the sinus as well as the duration of separated flow during the pulse cycle are affected by the geometrical variations. In view of the significance of the reversed flow zones and of the accompanied low shear regions in atherogenesis the geometry-dependent flow separation characteristics in the sinus is of substantial interest. PMID- 2319761 TI - Computer model of an inhomogeneous human torso. AB - Based on the atlas of sectional human anatomy, a three dimensional computer model of a human torso, including four cavities of the heart (LV, RV, LA, RA), two lobes of the lung and the body surface, and a three dimensional model of the myocardium is introduced. The torso model, with more than 10,000 surface triangles, depicts the structures and appropriate proportions of the internal organs, especially of the heart. Algorithms for the model construction are given in detail and the validity of the models for the purpose of simulation research into the electrocardiogram is discussed. PMID- 2319762 TI - A model approach to in situ coronary autoregulation. AB - Pressure and flow waveforms were recorded at the entrance of the circumflex coronary artery in anaesthetized dogs during artificial constriction and release of the aorta which caused noticeable variations in the coronary perfusion pressure. The beat-to-beat mean diastolic flow resulting from the autoregulation of the coronary bed in response to the pressure changes was analysed on the basis of a simple model. Flow variations were interpreted as the result of an active mechanism, triggered by the pressure changes and affecting the elastic behaviour of the vessels. The timing and the main characteristics of this response mechanism, after constrictions of varying duration, were evaluated and are discussed. The predicted variations in vessel distensibility and cross-sectional area were compared with data quoted in the literature, showing that the results of this procedure are compatible with those of in vitro measurements on isolated microvessels. PMID- 2319763 TI - Patient realignment in magnetic resonance imaging of the head: an algorithm using mathematical morphology for feature extraction. AB - To develop a technique for automatic patient realignment in magnetic resonance imaging (MRI), it is essential to extract key features automatically from the various slices of the head as accurately as possible. Such features include the brain, the brain stem, the pons, the corpus callosum and the cerebellum. A feature extraction algorithm has been developed which is based on thresholding a region to a common grey level and then applying mathematical morphology to produce a binary regular region. In addition, a region-filling algorithm has been developed to obtain the complete feature. The scans derived from the T1 spin lattice relaxation time, which are the fastest of the MRI scans, are used in patient realignment to provide highly textured images. These are difficult to segment using conventional thresholding or edge enhancement techniques due to their 'grainy' appearance, which makes it difficult to isolate key features from the other components found in the slice. We have developed a method for the accurate extraction of the corpus callosum, the cerebellum and the brain area in a sagittal scan of the head. This is carried out by selective thresholding designed to remove the low texture content and then applying morphological techniques. PMID- 2319764 TI - Evaluation of Euler's angles with a least squares method for the study of lumbar spine motion. AB - To analyse intervertebral movements, methods with a high level of accuracy are required. Stereoradiographic methods have been used for a number of years to describe intervertebral movements, but their major problem is to identify the same anatomical landmarks, not only on the pair of radiographs used for three dimensional reconstruction, but also on all the pairs used to analyse the displacements. To minimize the errors due to the incorrect identification of anatomical landmarks, a least squares method to resolve the parameters of Euler's angles was validated by means of measurements made on a spine obtained from a cadaver. The accuracy of this method varied between 0.69 degrees and 0.71 degrees in rotation and between 0.28 mm and 0.77 mm in translation. In addition, this method significantly corrected the position of the anatomical landmarks. Euler's angles, used with a least squares estimate, can provide accurate and precise results. PMID- 2319765 TI - Recruitment, force and fatigue characteristics of quadriceps muscles of paraplegics isometrically activated by surface functional electrical stimulation. AB - This study deals with the recruitment characteristics of unfatigued electrically stimulated quadriceps muscles of paraplegic subjects and with the time-dependent force output of these muscles under sustained stimulation conditions. Both these aspects of the performance of paralysed stimulated muscles were studied under isometric conditions and at different muscle lengths. The forces in the knee joint resulting from stimulation of the quadriceps were also calculated. Recruitment force curves due to a ramp-like stimulation function indicated a strong dependence on muscle length and demonstrated a sigmoid-shaped curve with three distinct regions: negligible force up to threshold stimulation intensity; rapid force increase; and levelling-off of the curve after which the force remains constant even though intensity is further increased. When normalized to the maximal force, recruitment was found to be independent of muscle length, generating a typical recruitment curve for every patient, under isometric stimulation. The peak forces were obtained at the same flexion angles previously published for normal subjects, but with much lower values. Muscle fatigue in tetanic isometric conditions, defined as the decrease in force due to sustained stimulation with fixed parameters, was found to be length dependent and to have a double exponential decay. The first is the acute force loss and is the more significant for functional purposes; the second is the more moderate and asymptotic region, in which partial force recovery in the form of bursts is observed. PMID- 2319766 TI - Dynamic analysis of a simplified bone model during the process of fracture healing. AB - The dynamic analysis of fracture healing is tackled numerically by means of a bone model which uses the finite element method. The model is of non-uniform cross-sectional area and moment of inertia. Shear and rotatory inertia are taken into account. Considerable variation of the upper natural frequencies is observed as the healing process progresses. The practical implications, as well as present limitations, of the technique are examined. PMID- 2319767 TI - Power spectrum analysis of fetal heart rate variability using the abdominal maternal electrocardiogram. AB - A signal analysis procedure is described for obtaining the power spectrum of the fetal and maternal heart rates as recorded from the abdomen. This technique, which includes the subtraction of an averaged maternal ECG waveform using a cross correlation function and the fast Fourier transform algorithm, enables the detection of all the fetal QRS complexes in spite of their coincidence with the maternal ECGs. The power spectrum of the fetal heart rates (FHR) obtained from 15 women at 32-41 weeks gestation were studied and two indices were measured which are related to the long term and short term variabilities in the FHR signal. It was found that quantitative evaluation of the FHR variability can be obtained using power spectrum analysis. PMID- 2319768 TI - Initiation of gait in normal subjects: a preliminary study. AB - The initiation of gait, from standing at rest to the toe-off of the second leg, was analysed in 15 normal subjects wearing shoes. Thirty-two parameters were identified and measured. The pattern of forces, angular movement and timing in this period are described and analysed. Two groups, one of 8 female subjects and another of 7 males, were compared statistically. Sex-related differences were found in the mediolateral and vertical forces as well as in which leg was the first to leave the ground. The values of all the parameters are given, as part of a database to be used in the future for diagnostic and assessment purposes in orthopaedics. PMID- 2319769 TI - A constant current device for bipolar electrical stimulation in vitro. PMID- 2319770 TI - An extendable modular endoprosthetic system for bone tumour management in the leg. AB - A modular endoprosthetic system has been developed at the Groningen University Hospital and the University of Twente. The system can bridge a defect resulting from the resection of a malignant bone tumour which has developed around the knee joint of a child. Since the other healthy leg continues to grow, the system includes an element whose length can be adjusted non-invasively by using an external magnetic field. In addition to this lengthening element, there are one hip and two knee components, connectors of various lengths, and fixation elements. The paper describes the elements of the modular endoprosthetic system. Tables are created by means of which the elemental composition of such an endoprosthesis can be determined for each individual patient. PMID- 2319771 TI - In vitro biomechanical study of female geriatric cervical vertebral bodies. AB - Compressive strength tests were conducted on fresh human geriatric female cervical vertebral bodies. Nineteen specimens were compressed to 50% of their initial height using an electrohydraulic testing device. The mechanical force deflection response was sigmoidal with continuously changing resistance. The mean cross-sectional area and bone mineral content (BMC) of the vertebral bodies progressively increased from C3 (area: 333.8 mm2, BMC: 1.56 g) to C6 (area: 499.7 mm2, BMC: 2.18 g). The maximum compressive force increased from 1060 N at C3 to 1787 N at C6. The stiffness and the energy absorbed at failure also increased from C3 to C6 (stiffness: 279.95 to 556.41 N mm-1, energy: 2.45 to 4.16 J). These parameters demonstrated a decreasing tendency from C6 to C7. The relatively higher biomechanical parameters at the sixth vertebral level compared with its caudad and cephalad counterparts may be due to the fact the transition of the cervical lordosis to thoracic kyphosis begins at this level. Furthermore, the change in the anatomy of the unicinate processes in the cervical column around this region may also be a contributing factor. PMID- 2319772 TI - Rapid management of intracranial hypertension to reverse transtentorial herniation. PMID- 2319773 TI - Diagnosis of acoustic neuroma by magnetic resonance imaging. PMID- 2319774 TI - A case of abdominal pain and diarrhea. PMID- 2319775 TI - Adolescent pregnancy in Tennessee. PMID- 2319776 TI - Scientific surgical meetings: why do we need them? PMID- 2319777 TI - Operative transluminal balloon angioplasty. Adjunct to coronary bypass for extended myocardial revascularization of more than 3000 lesions in 1000 patients. AB - Operative transluminal coronary artery balloon angioplasty has been used for over 3000 lesions in 1000 patients since 1980. Initially it was only used for distal stenoses not accessible to coronary bypass grafting in 200 patients. Recatheterization of patients who had intraoperative transluminal balloon angioplasty of the proximal left anterior descending, right, and circumflex coronary arteries 3 years previously revealed excellent patency of both the bypass grafts and the dilated native coronary arteries. This observation supports the thesis that with properly constructed bypass anastomoses competitive flow does not significantly mandate graft thrombosis. Subsequently, intraoperative balloon angioplasty has been performed for both proximal and distal stenoses in 800 patients to improve native coronary artery perfusion and maximize revascularization. Follow-up from 1 to 7 years revealed perioperative myocardial infarction in 21 patients (2.1%) and death in 19 patients (1.9%). Recatheterization from 1 to 7 years after the operation in 51 patients (41 with symptoms) revealed that patency was almost as prevalent in arteries subjected to angioplasty (82%; 137/167) as in bypass grafts (84%; 102/122). Intraoperative balloon angioplasty appears to improve coronary artery perfusion without detrimental competitive flow when used with bypass grafts. PMID- 2319778 TI - The lateral limited thoracotomy incision: standard for pulmonary operations. AB - Four hundred sixty-eight consecutive thoracotomies for which the lateral limited thoracotomy incision was used are reviewed (1978 to 1988). The limited incision is a lateral muscle-splitting incision with preservation of the latissimus dorsi, splitting of the serratus anterior, and cutting of only the intercostal muscles without rib resection. Patients were designated unsuitable for operation if (1) biopsy-proved distant metastasis existed, (2) mediastinoscopy revealed extranodal metastasis, or (3) severe respiratory compromise resulted in shortness of breath at rest with a forced expiratory volume in 1 second of less than 0.75 L (four patients). Mean patient age was 60.9 (+/- 15.7) years. Surgical procedures included lobectomy (n = 317), pneumonectomy (n = 41), wedge resection (n = 82), resections of blebs or bullae (n = 17), thoracotomy and biopsy for unresectable lesion (n = 6), and decortication (n = 5). Pathologic analysis revealed 354 malignant tumors, 102 benign lesions, and 12 carcinoids. The perioperative mortality rate was 0.85% (4/468) and major morbidity was present in 2.9% (14/468). Mean operative time was 73.1 (+/- 32.2) minutes with a blood loss resulting in a mean decrease of the hematocrit value of 2.6 (+/- 2.5) gm; three patients were given a total of 7 units of blood. Most patients do not require a stay in the intensive care unit postoperatively (less than 10%). Hospital stay postoperatively was a mean of 6.1 (+/- 2.9 days. The limited incision is a significant factor in decreasing operative time, blood loss, postoperative pain and morbidity, and cost. PMID- 2319779 TI - Congenital bronchopulmonary malformations. Diagnostic and therapeutic considerations. AB - Congenital bronchopulmonary malformations are uncommon but potentially life threatening anomalies of infants and children. Between 1970 and 1988, 45 patients from birth to 13 years of age (23 boys and 22 girls) underwent evaluation and treatment for bronchopulmonary malformations. Thirty-seven had solitary lesions: bronchogenic cyst (n = 13), cystic adenomatoid malformation (n = 9), congenital lobar emphysema (n = 6), pulmonary sequestration (n = 6), arteriovenous malformation (n = 2), and bronchial atresia (n = 1). Eight additional patients had two simultaneous abnormalities and three patients had congenital diaphragmatic hernias. Twenty-one patients had respiratory symptoms, which were severe in seven. Twelve had pulmonary infection and 10 patients were completely free of symptoms. Plain chest roentgenogram was the only diagnostic imaging performed in 11 patients. Thirteen patients underwent computed tomographic scan, but in only four was it essential for diagnosis. Prenatal ultrasonography in three patients demonstrated cystic adenomatoid malformation in two, with one false negative study. Postnatally, ultrasonography was also useful in establishing the diagnoses of cystic adenomatoid malformation and pulmonary sequestration. Thoracotomy with excision of the lesion by lobectomy or pneumonectomy resulted in survival of 42 patients (93%). Three deaths in neonates were due to pulmonary hypoplasia and hypertension. Two of them had concomitant diaphragmatic hernia; the other had a cystic adenomatoid malformation and died despite the use of postoperative extracorporeal membrane oxygenation. These data demonstrate that congenital bronchopulmonary malformations usually can be diagnosed by plain chest x-ray films. Ancillary studies such as ultrasonography or computed tomography may occasionally be necessary. Combinations of the different types of bronchopulmonary malformations occurred frequently. All lesions, including symptomatic lesions in neonates, can be managed surgically soon after diagnosis. PMID- 2319780 TI - Clinical experience with the silicone tracheal prosthesis. AB - The superiority of using the patient's own tissue for tracheal reconstruction is acknowledged. When this is impossible an alternate method is mandatory. From 1970 to 1988, 62 patients with benign and malignant tracheal stenosis had airway continuity established with a silicone tube. A straight graft was used in 48 patients. Twenty-eight had strictures, two tracheoesophageal fistulas and strictures, five primary malacia, and 13 malignant tumors. In 20 with noncancerous tracheal obstruction the airway was resected and a graft interposed. Distal suture line granulomas developed in six of these patients. Two had subglottic granulomas. One had graft dehiscence after dissolution of absorbable suture material. This graft was replaced with a silicone T tube. Four patients with end-to-end anastomosis of the graft to the trachea died in 6 to 12 months. Six others were lost to follow-up. In 15 of the 48 with benign disease the stent was placed within the lumen. Six in this group died. Thirteen of the 48 patients had a malignant tumor. In six the tube was used for palliation; none are alive. Seven underwent resection; five are living 1 to 8 years after the operation, two died of their disease in 1 1/2 to 2 years, and two of the five living are undergoing irradiation for recurrent cancer. Fourteen individuals with tracheocarinal malignancy received a bifurcated graft. All six patients with a palliative intraluminal stent died. Among eight individuals, four died of disease in 1 to 4 years. Four are alive, but two have suture line granulomas and two are undergoing irradiation for residual carcinoma. Mediastinal infection, mucus encrustations of the intraluminal prosthesis, and impedence of pulmonary secretions across long tubular segments have not been manifest. These silicone tubes are well tolerated and function satisfactorily as an airway. PMID- 2319781 TI - Nuclear scan-guided rib biopsy. AB - The bone scan is a sensitive screening device that is frequently used to stage the condition of patients with known or suspected malignant disease. Abnormal findings on bone scan are associated with corresponding normal findings on radiographs in approximately 50% of cases. Definitive tissue diagnosis of the bone lesion is often needed to determine optimal therapy, but localization of the lesion is imprecise unless it is palpable. Use of the nuclear scan to localize and mark the rib enhances the precision of the biopsy procedure. Thirty-three consecutive patients with cancer who had bone scans suggestive of rib abnormalities underwent nuclear scan-guided biopsy. Each patient had a repeat localizing scan with a maximum permissible dose of technetium 99m radionuclide on the day of the planned biopsy. The site of abnormality was marked with methylene blue injected into the skin overlying the lesion and down to the periosteum at the specific site. The patient was then taken to the operating room and the marked area was excised through a small incision. Pathologic abnormality was identified in all but one of the resected specimens, an accuracy rate of 97%. Despite a presumed or proved diagnosis of cancer in 33 patients, 16 specimens (48%) were benign. There were no complications associated with this technique, which reduces the morbidity and increases the precision of rib biopsy. PMID- 2319782 TI - Mitral valve repair: results and the decision-making process in reconstruction. Report of 275 cases. AB - From January 1975 to June 1988, 275 patients underwent mitral valve repair for mitral regurgitation, pure (148 patients) or associated with mitral stenosis (127 patients). Patients with pure mitral stenosis were excluded from this study. The cause of mitral regurgitation was rheumatic in 180 patients (aged 28.6 +/- 1.2 years, mean +/- standard error of the mean) and degenerative in 84 patients (aged 54.7 +/- 1.5 years). Fifty-nine percent of the patients were in New York Heart Association classes III and IV before the operation. Intraoperative assessment of the mitral valve led us to identify four major mechanisms of mitral regurgitation: (1) restriction of leaflet motion by fibrosis (group I, 63 patients); (2) enhancement of leaflet motion by leaflet and chordal extension and prolapse (group II, 139 patients), (3) combination of both (group III, 64 patients); and (4) isolated dilatation of the anulus (group IV, 10 patients). One hundred sixty-one patients had isolated mitral disease and 114 had associated aortic or tricuspid valve disease, or both. The hospital mortality rate was 4.0%. Follow-up was 96% complete and totaled 1247.47 patient-years. At 13 years' follow up, the survival rate was 93.0% +/- 6.8% in group I, 90.0% +/- 6.0% in group II, and 96.6% +/- 4.6% in group III. Freedom from reoperation was 78.1% +/- 21.0%, 83.2% +/- 18.9%, and 79.6% +/- 16.2%, respectively. Freedom from embolism was 94.7% for the whole series. In patients with isolated mitral valve repair, the cumulative morbidity was significantly higher in groups I (6.3 +/- 2.0%/pt-yr) and III 6.3% +/- 1.7%/pt-yr) than in group II (2.5% +/- 0.9%/pt-yr, p less than 0.05). Multivariate analysis identified age and associated tricuspid valve disease as significant predictors of reoperation (p less than 0.01 for both factors). These results suggest that conservative surgery should be used with caution in group I and III patients. In contrast, indications for mitral valve repair should be extended in group II patients. This observation has important clinical implications since, in Western countries, valve prolapse tends to be a major cause of mitral regurgitation. PMID- 2319783 TI - Valve replacement in the young patient with rheumatic heart disease. Review of a twenty-year experience. AB - During a 20-year period 303 young subjects between 9 and 20 years of age (mean, 16.2 +/- 2.72 years) with rapid and relentlessly progressive valvular disease from rheumatic fever underwent valve replacements. The Starr-Edwards ball valve prosthesis remains the device of choice, although other valves have been implanted. The overall hospital mortality rate was 9.6% in the mitral valve, 3.5% in the aortic valve, and 4.2% in the double valve replacement groups. Actuarial survival at 10, 15, and 20 years was 78.4% (+/- 3.3%), 70.0% (+/- 5.8%), and 59.3% (+/- 11.1%), respectively, for patients with mitral valve replacement. The rates for aortic valve replacement were 85.9% (+/- 4.6%) at 10 and 15 years and 72.7% (12.8%) at 20 years. In the double valve replacement group the survival rates after 5 and 10 years were 79.9% (+/- 5.1%). The incidence of thromboembolism was 0.41, 0.59, and 1.04 per 100 patient-years for the mitral, aortic, and double-valve prostheses, respectively. The prospect of childbearing seems promising in those young women who were subsequently married. Our favorable and gratifying experience in this review bears testimony to the physiologic advantages of the Starr-Edwards valve as the device of choice in the rehabilitation of patients with advanced and severe valvular disease after rheumatic fever. PMID- 2319784 TI - Closed versus open mitral commissurotomy in pure noncalcific mitral stenosis: hemodynamic studies before and after operation. AB - Controversy persists regarding whether the efficacy of closed instrumental mitral commissurotomy compares well enough with that of open commissurotomy to warrant its continued use. The purpose of this study was to compare the results of operation as determined by catheterization studies in 63 patients with pure, severe, and noncalcified mitral stenosis. The patients were randomly assigned to one of two groups: thirty-two patients were operated on by the closed technique (group I) and 31 by the open technique (group II). All patients underwent left sided and right-sided catheterization before and 4 months after operation. Preoperatively the two groups were statistically similar with regard to major clinical data and hemodynamic findings. There were no deaths at operation or systemic embolism in the two groups. The prevalence of surgically induced mitral regurgitation was similar in the two groups (12.4% versus 12.9%). Pulmonary arterial pressure and arteriolar and total pulmonary vascular resistance decreased significantly in the two groups. Pulmonary capillary wedge pressure decreased from 23.3 +/- 8.5 to 15.8 +/- 7 mm Hg in group I (p less than 0.001) and from 23.7 +/- 6 to 14 +/- 5.8 mm Hg in group II (p less than 0.001). Cardiac index increased from 2.86 +/- 0.84 to 3.14 +/- 0.78 L/min/m2 in group I, but this increase did not reach statistical significance. In group II cardiac index increased from 2.89 +/- 0.6 to 3.6 +/- 0.6 L/min/m2 (p less than 0.005). The mean and end-diastolic transmitral pressure gradients decreased significantly in the two groups, but the decrease was statistically greater in the open mitral commissurotomy group (p less than 0.001). Mitral valve area increased from 0.82 +/- 0.18 to 1.4 +/- 0.40 cm2 in group I (p less than 0.01) and from 0.84 +/- 0.15 to 2.14 +/- 0.53 cm2 in group II (p less than 0.001). The mean increase in mitral valve area was 0.61 cm2 in group I and 1.34 cm2 in group II (p less than 0.001). At exercise, in patients with resting pulmonary capillary wedge pressures of 18 mm Hg or less, cardiac index increased by 36% in group I (23 patients) and 48% in group II (24 patients), because of a smaller mitral valve area in group I (1.61 +/- 0.39 cm2) than in group II (2.45 +/- 0.65 cm2). Thus open commissurotomy improved hemodynamic values to a greater extent than closed commissurotomy at both rest and exercise.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2319785 TI - Serial assessment of ventricular performance after valve replacement for aortic stenosis. AB - The purpose of this investigation was to examine changes in cardiac function after aortic valve replacement in patients with chronic aortic stenosis. Eleven consecutive patients with severe aortic stenosis were studied by radionuclide angiocardiography before; after 1, 2, 4, 6, 8, and 18 to 24 hours; and late after operation. Measurements of cardiac output, mean systemic blood pressure, heart rate, and left ventricular ejection fraction were similar before and immediately after operation. Significant early changes were observed in pulmonary capillary wedge pressure (27 to 13 mm Hg; p less than 0.001), left ventricular end diastolic volume (214 to 166 ml; p less than 0.01), pulmonary blood volume (700 to 462 ml/m2; p less than 0.01), and right ventricular ejection fraction (0.54 to 0.68; p less than 0.001). A radionuclide angiocardiogram acquired a mean of 3.5 months after operation revealed increased resting left ventricular ejection fraction (0.49 to 0.58; p = 0.05), decreased end-systolic volume (91 to 59 ml; p less than 0.05), and decreased end-diastolic volume (166 to 135 ml; p less than 0.02) compared with measurements before operation. Improved exercise tolerance occurred in nine patients. The significant change in function during the early period after valve replacement was a maintenance of baseline cardiac output at a reduced level of left ventricular filling. Several months after operation, left ventricular volumes decreased further, resting ventricular performance was improved, and improved maximal exercise function was demonstrated. These changes probably reflected morphologic normalization after aortic valve replacement. PMID- 2319786 TI - Replacement of the ascending aorta. Early and late results. AB - From 1978 through 1987, 225 patients underwent operations that included replacement of the ascending aorta. One hundred twenty-three patients underwent composite aortic valve and ascending aortic replacement, 30 had aortic valve replacement with separate graft replacement of the ascending aorta, and 72 underwent replacement of the ascending aorta without aortic valve replacement. Thirty-one (13.8%) in-hospital deaths occurred. Univariate testing of preoperative and operative variables followed by logistic regression analyses identified miscellaneous aortic disease, coronary artery bypass grafting, aortic arch replacement, emergency operation, surgical date (1978 to 1983), and age (all p less than 0.05) as factors having independent association with in-hospital mortality. Follow-up of in-hospital survivors (mean interval 46 months, range 8 to 123 months) documented an overall 5-year survival rate of 76%, 83% after primary operation and 37% after reoperation. Univariate analyses followed by multivariate testing indicated that previous operation (p less than 0.0001) and a history of preoperative neurologic symptoms (p = 0.021) were associated with decreased late survival. At follow-up 88% of late survivors were free of symptoms. Seven patients have undergone reoperation 1 day to 69 months postoperatively. Although the in-hospital mortality for operations that include ascending aortic replacement exceeds that for isolated aortic valve replacement, the late death rate and rate of reoperation are low. PMID- 2319787 TI - Elective hypothermic cardiopulmonary bypass and circulatory arrest for spinal cord protection during operations on the thoracoabdominal aorta. AB - Resection of aneurysms of the entire descending thoracic aorta and segments of the abdominal aorta is associated with a substantial incidence of spinal cord ischemic injury, particularly in patients with aortic dissection. Since hypothermia has a protective effect on spinal cord function, we evaluated a technique of total cardiopulmonary bypass with periods of hypothermic circulatory arrest and low flow (rectal/bladder temperatures of 15 degrees to 19 degrees C) in five patients requiring replacement of the entire descending thoracic and the upper abdominal aorta and judged to be at high risk for the development of spinal cord injury. All patent lower intercostal and lumbar arteries were preserved or reimplanted during the hypothermic interval. There was one hospital death. None of the four survivors had a new spinal neurologic deficit, renal or cardiac dysfunction, or required reoperation for bleeding. Transfusion of blood products was not excessive. Severe pulmonary dysfunction necessitating tracheostomy occurred in one patient and contributed to his death 7 weeks postoperatively. The remaining three patients are well 8 to 36 months postoperatively. This initial experience suggests that hypothermic perfusion and circulatory arrest can be safely implemented in selected patients who require extensive aortic resections and who are at substantial risk for the development of spinal cord injury. Further evaluation of this technique is warranted. PMID- 2319788 TI - Preventive effect of Fluosol-DA for paraplegia encountered after surgical treatment of the thoracic aorta. Preliminary results in a dog model. AB - The effectiveness of Fluosol-DA (Green Cross Corporation, Osaka, Japan) on circulatory dynamics and neurologic outcome in dogs with ischemic spinal cord injury produced by aortic crossclamping was tested. The control group (receiving saline solution) had an elevated mean aortic proximal pressure (112.9 +/- 30.2 mm Hg versus 175.3 +/- 20.5 mm Hg, p greater than 0.05) and a drastic drop in mean distal aortic pressure (112.9 +/- 30.2 mm Hg versus 29.8 +/- 11.2 mm Hg, p less than 0.05). Although the same trend occurred in dogs treated prophylactically with Fluosol-DA, these changes were not statistically significant. However, there was a significant difference in mean distal aortic pressure during the ischemic phase between the two groups (58.9 +/- 16.0 mm Hg versus 29.8 +/- 11.2 mm Hg, p less than 0.05). Postoperatively all animals had mean arterial pressures within the normal range. All dogs in the control group were paraplegic (partial or complete); the treatment group had one dog with partial paraplegia. The difference between the mean neurologic scores of the two groups was of high statistical significance (3.7 +/- 0.5 versus 1.6 +/- 1.0, p less than 0.05). Our preliminary results show that prophylactic use of Fluosol-DA has favorable effects on hemodynamics and neurologic outcome in dogs with spinal cord ischemia produced by aortic crossclamping. The high propensity of the drug to carry oxygen and carbon dioxide and to provide nutritional support to the ischemic area with resultant improvement in local microcirculation and blood rheology are some speculative mechanisms advocated for these changes. PMID- 2319789 TI - Risk factors for pulmonary thromboendarterectomy. AB - Pulmonary thromboendarterectomy is being performed with increasing frequency for incapacitating pulmonary hypertension caused by chronic large-vessel pulmonary embolism. However, patient-related risk factors and procedural complications associated with morbidity and mortality have not been fully defined. From Oct. 1, 1984, to April 10, 1989, we performed pulmonary thromboendarterectomy using deep hypothermia and circulatory arrest in 127 consecutive patients (62.2% male, mean age 50 +/- 16 [standard deviation], range 20 to 82 years) in whom the exposure and dissection of the pulmonary arteries and methods for myocardial protection have been standardized. End points for univariate and multivariate analyses of risk factors were reperfusion pulmonary edema leading to respiratory insufficiency as defined by ventilator dependency (greater than or equal to 5 days) (31.5%, 39/124) and hospital mortality (12.6%, 16/127). Multivariate analyses showed that ascites and need for 4 units of blood or more predicted ventilator dependency (p less than 0.03). Increased cardiopulmonary bypass times predicted both end points (p less than 0.03 to less than 0.0001), and failure to achieve at least a 50% reduction in pulmonary vascular resistance strongly predicted hospital death (p less than 0.0001). However, other factors that exhibited trends for association with one of the end points may prove important with a larger sample size. A hospital mortality rate of 12.6% for pulmonary thromboendarterectomy is acceptable when compared with approximately 25% for heart-lung transplantation, which is the only therapeutic alternative. Increased ventilator dependency and hospital mortality can be anticipated with longer cardiopulmonary bypass times and inadequate reduction of pulmonary vascular resistance. PMID- 2319790 TI - Neonatal aortic stenosis. AB - Aortic stenosis in the neonate has been associated in the past with a high operative mortality. As a result, in the current era of percutaneous balloon dilatation, the optimal mode of therapy remains controversial. An approach of stabilization with cardiopulmonary bypass, followed by relief of left ventricular outflow tract obstruction, was used at three institutions, and the results are presented. During the period 1983 to 1989, 40 neonates with isolated aortic stenosis and patent ductus arteriosus or coarctation of the aorta, or both, underwent operative therapy. Ages ranged from 1 to 30 days, median of 12 days, including 17 patients in the first week of life. There were 30 boys and 10 girls; weights ranged from 2.5 to 5.5 kg with a mean of 3.6 kg. Perioperative conditions included congestive heart failure in 38 and mitral regurgitation in 16; left ventricular-aortic gradients ranged from 15 to 130 mm Hg, with a mean of 67 mm Hg. There were 30 open valvotomies and 10 transventricular dilatations. The hospital survival rate was 87.5% (35/40) with no significant difference between the methods of valvotomy (9/10 in the transventricular dilatation group, 90%; 26/30 in the open valvotomy group, 87%). Although multiple methods of perfusion and valvotomy were used, the single unifying factor of cardiopulmonary bypass stabilization was present in all 40 patients. No significant difference in survival was noted between institutions, methods of cardiopulmonary bypass, cardiopulmonary bypass times, crossclamp times, or method of valvotomy. There have been five reoperations, with one late death in a patient requiring mitral valve replacement and an apical-aortic conduit. One sudden death occurred; autopsy revealed endocardial fibroelastosis. Results demonstrate that in the three institutions using the methods described, a high operative and late survival rate is possible. The results of this technique, against which percutaneous dilatation should be compared, are standard in the current era. PMID- 2319791 TI - Intrauterine versus postnatal repair of created pulmonary artery stenosis in the lamb. Morphologic comparison. AB - Experimental lamb models were used for intrauterine creation of pulmonary artery stenosis and later intrauterine repair or postnatal repair. Intrauterine creation of pulmonary artery stenosis was performed in 23 fetal lambs at 90 +/- 1 days of gestation. Eight lambs underwent intrauterine repair of pulmonary artery stenosis at 135 +/- 1 days of gestation and were studied 110 +/- 13 days after repair. Seven lambs underwent postnatal repair at 57 +/- 9 days after birth and were studied 162 +/- 32 days after repair. Eight fetal lambs with unrepaired pulmonary artery stenosis were studied 89 +/- 18 days after birth. All study lambs were compared with normal control lambs. The systolic right ventricular pressure was significantly higher after unrepaired stenosis (78.6 +/- 6.8 mm Hg) than in other lambs, but there was no statistically significant difference after intrauterine repair (23.3 +/- 2.9 mm Hg), postnatal repair (25.9 +/- 3.4 mm Hg), and normal lambs (21.6 +/- 1.1 mm Hg). The systolic pulmonary artery pressure was also not statistically different in these three groups. The weight measurements were age adjusted for comparison of postnatal and intrauterine repair with normal lambs. The adjusted heart weights were similar in the three groups. The comparison of the adjusted heart weight/adjusted body weight ratio (10(-3) showed a significantly higher ratio in postnatal repair (7.4 +/- 0.1) than in intrauterine repair (6.1 +/- 0.1). The adjusted right ventricular weight/adjusted left ventricular weight ratio was significantly higher in the postnatal repair group (0.71 +/- 0.01) than in both the intrauterine repair group (0.59 +/- 0.01) and normal lambs (0.59 +/- 0.01). The transverse myocyte diameter was not statistically different in all groups of animals and there were no ultrastructural changes even when the pulmonary stenosis was unrepaired. We conclude that intrauterine repair was more satisfactory than postnatal repair in terms of age-adjusted heart weight results, but we did not find any advantages of intrauterine repair in terms of histologic and ultrastructural changes. PMID- 2319792 TI - Surgical approach to isolated mediastinal lymphoma. AB - With the aim of assessing the role of surgery in the management of isolated mediastinal lymphoma, we have reviewed the data of 123 operations performed on 102 patients (64 with Hodgkin's disease and 38 with non-Hodgkin's lymphoma). One death and four major complications occurred in these patients. Macroscopically radical resection was performed in 14 patients who are free of disease after 1 to 14 years. Debulking resection was performed in five patients: Three are alive after 5 to 11 years and two died after 36 and 40 months. Ten patients (seven with non-Hodgkin's lymphoma and three with Hodgkin's disease) had residual mediastinal masses of more than 2 cm after chemotherapy; to assess the nature of the lesion (fibrosis or residual disease), we subjected these patients to surgical restaging of the mediastinum: Results were negative in seven and positive in three. We conclude that open biopsy is indispensable to obtain good tissue specimens suitable for histologic and immunohistochemical assessment. Biopsy must be performed as a major surgical procedure to avoid reoperation: Mediastinoscopy and sternal splitting incisions proved the most reliable approaches. Locally radical or debulking resection might be considered in selected cases to enhance long-term results. PMID- 2319793 TI - Evaluation of postoperative flow capacity of internal mammary artery. AB - The internal mammary artery has been advocated for use in coronary artery bypass grafting because of its excellent long-term patency. We compared the flow capacities of internal mammary artery and saphenous vein grafts under exercise conditions by means of radionuclide angiocardiography. Fifty-two patients were divided according to the type of bypass graft done to the left anterior descending artery: group 1 comprised 27 patients with the internal mammary artery graft, and group 2 included 25 patients with the saphenous vein graft. Saphenous vein grafts were placed into the right and circumflex systems. Before the operation, global and regional ejection fractions decreased similarly in both groups with exercise. After the operation, the global ejection fraction measured in groups 1 and 2 increased significantly from 54% +/- 2% to 57% +/- 2% and from 54% +/- 1% to 60% +/- 2%, respectively, the anteroseptal ejection fraction from 29% +/- 1% to 32% +/- 2% and from 29% +/- 1% to 35% +/- 1%, respectively, and the apical ejection fraction from 75% +/- 3% to 82% +/- 2% and from 77% +/- 2% to 86% +/- 2%, respectively. There were no differences in exercise-induced increases in the global and regional ejection fractions between groups 1 and 2. Six patients in group 1 had exercise-induced wall motion abnormalities at the anteroseptal and/or apical segments. In contrast, patients in group 2 had no exercise-induced wall motion abnormalities at these segments (p less than 0.05, group 1 versus group 2). Results of this study show that internal mammary artery grafts respond to the increased blood flow demand of exercise in essentially the same way as saphenous vein grafts. However, there seems to be a slightly greater potential for inadequate flow in patients with the internal mammary artery graft, as evidenced by the small group of patients with exercise-induced wall motion abnormalities. PMID- 2319794 TI - Comparative anatomic studies of various arterial conduits for myocardial revascularization. AB - Comparison was made between the morphologic condition of the left anterior descending artery and four arterial conduits: the internal mammary, right gastroepiploic, inferior epigastric, and radial arteries, harvested from 17 patients (aged 15 to 85 years, mean 64 years) who had died of nonvascular diseases. Proximal, mid, and distal segments were examined microscopically. The internal mammary artery was elastic, but the others were muscular. In all four conduits, atherosclerosis was absent to mild, the internal elastic lamina showed only minimal defects, and the vasa vasorum were confined to the adventitia. In all cases the left anterior descending artery showed mild to severe atherosclerosis and substantial defects in the internal elastic lamina with penetration of the vasa vasorum into the media and intima. Comparison of the mean distance (+/- standard deviation) from the lumen to the outermost portion of the media for the left anterior descending artery (320 +/- 63 microns) with the four conduits gave comparable values for the internal mammary artery (350 +/- 92 microns); p = not significant) and the right gastroepiploic artery (291 +/- 109 microns; p = not significant), versus 529 +/- 52 microns; p less than 0.002) for the radial artery and 249 microns (+/- 87 microns) (p less than 0.04) for the inferior epigastric artery (Kruskal-Wallis and Mann-Whitney U tests). The relatively scanty presence of smooth muscle cells in the thin-walled media of the internal mammary artery combined with a well-formed internal elastic lamina, even at advanced age, may be an important cause for its low susceptibility to atherosclerosis and a major determinant in its superior long-term patency as a coronary artery bypass graft. This finding emphasizes the justification of continued use of the ideally matching internal mammary artery, either as in situ or free graft, in coronary artery bypass grafting. In contrast to the thick walled radial artery, which may be relatively prone to ischemia, an acceptable long-term patency of the inferior epigastric artery and right gastroepiploic artery, if harvested as pedicled grafts, is anticipated. PMID- 2319795 TI - Bilateral internal mammary artery grafts for coronary artery bypass operations in children. AB - We performed myocardial revascularization with bilateral internal mammary arteries in eight children for coronary artery complications consequent to Kawasaki disease. Subjects included seven boys and one girl, ranging in age from 3 to 13 years (mean age, 8.3 +/- 3.4 years). The body surface area ranged from 0.65 to 1.65 m2 (average, 1.08 +/- 0.35 m2). Three patients had a previous myocardial infarction. The right internal mammary artery was anastomosed to the right coronary artery and the left internal mammary artery was sutured to the left anterior descending artery in all patients. The patients received an average of 2.4 grafts. Magnifying loupes of 3.5 X were used for anastomosis with 8-0 monofilament polypropylene sutures. Subjects were followed up from 12 to 38 months (23 +/- 10.8 months) after operation. All were doing well with no recurrence of angina, and body development was normal, including the sternum and thorax according to chest x-ray films and computed tomography of the chest. Patency of the bilateral internal mammary arteries was 100% in the early (within 1 month) postoperative period and remained so in the late (over 1 year) postoperative period. Anastomotic junctions between the internal mammary artery and the coronary artery developed well angiographically in the late postoperative period. The internal mammary artery is the graft of choice for pediatric myocardial revascularization because of its excellent long-term patency and growth potential. Bilateral internal mammary arteries should be used whenever indicated, and the use of bilateral internal mammary arteries did not adversely influence chest wall development in the children. PMID- 2319796 TI - Effects of left heart bypass on right ventricular performance. Evaluation of the right ventricular end-systolic and end-diastolic pressure-volume relation in the in situ normal canine heart. AB - Although left heart bypass has gained popularity as a powerful technique to assist the severely failed left heart, apparent right heart failure has often developed during the bypass procedure. We investigated whether the coexisting right heart failure is attributable to the left heart bypass in 16 open-chest dogs. We evaluated the effects of left heart bypass on the right ventricular systolic properties by the slope of the end-systolic pressure-volume relation and its effects on the diastolic properties by chamber compliance. Overall right ventricular performance was assessed by the end-diastolic pressure versus cardiac output relationship. The left heart bypass decreased the slope slightly when the assisted flow ratio exceeded 75% (-14% +/- 8% at the assisted flow ratio of 100%, p less than 0.02) and thus had a deleterious influence on right ventricular performance. The left heart bypass, on the other hand, had a counteracting beneficial influence on right ventricular performance through the increase in chamber compliance (38% +/- 5%, p less than 0.01) and the decrease in pulmonary arterial input resistance (-15% +/- 12%, p less than 0.01). The net effect of the left heart bypass was the increase in cardiac output (20% +/- 2%, p less than 0.05) for any given right ventricular end-diastolic pressure. We conclude that in normal hearts the left heart bypass augments right ventricular performance. We ascribe these beneficial effects to diastolic ventricular interdependence and afterload unloading. PMID- 2319797 TI - The influence of extracorporeal circulation and hemoseparation on red cell deformability and membrane proteins in coronary artery disease. AB - Extracorporeal circulation and hemoseparation may lead to coupled mechanical and chemical blood trauma and thus influence red cell deformability. Ten patients with coronary artery disease underwent coronary bypass. Patients' blood samples were drawn preoperatively, after extracorporeal circulation, and after hemoseparation. Ten healthy adults served as control subjects. Red blood cell deformability was determined by direct microscopic observation of red blood cells subjected to shear stresses of 1.2 to 13.3 Pa with a counter-rotating rheoscope. Red cell membrane proteins were separated by one-dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. At 1.2 Pa, preoperative red cell deformability was significantly greater in patients with coronary artery disease than in control subjects. Neither extracorporeal circulation nor hemoseparation changed red cell deformability significantly. Electrophoretic separation of membrane proteins failed to show any quantitative or qualitative differences between patients and control subjects. Moreover RBC membrane proteins of red blood cells in the patients were not altered as a result of extracorporeal circulation or hemoseparation. The preoperatively increased red cell deformability in the patients may be drug-induced. Our data suggest that the extracorporeal circulation and hemoseparation techniques used in this study do not lead to red blood cell damage. PMID- 2319798 TI - Invited letter concerning: hemolysis after cardiopulmonary bypass. PMID- 2319799 TI - Reply to: Surgical treatment of carcinoma of the thoracic esophagus and cardia. PMID- 2319800 TI - Multiple-vessel coronary revascularization using both in situ mammary arteries and a free inferior epigastric artery. PMID- 2319801 TI - Unusual case of acquired benign tracheoesophageal fistula caused by an esophageal foreign body. PMID- 2319802 TI - Treatment of spontaneous pneumothorax with Heimlich flutter valve. PMID- 2319803 TI - Early thromboembolism after atrial septal defect repair. PMID- 2319804 TI - Preferential uptake of benzoporphyrin derivative by leukemic versus normal cells. AB - Benzoporphyrin derivatives (BPDs) are photosensitizers, which fluoresce strongly at 690 nm, and may be candidates for various applications of photodynamic therapy (PDT). Fluorescence-activated cell sorting (FACS) analysis, subsequent to ultraviolet light excitation, revealed pronounced differences in red fluorescence between leukemic cell lines (HL60, K562 and L1210), leukemic clinical isolates, and normal human or murine bone marrow cells incubated with BPD. These observed differences in BPD-mediated fluorescence provide the rationale for sorting leukemic from normal cells via FACS or may constitute a novel method for extracorporeal purging of remission marrow by photodynamic therapy in autologous bone marrow transplantation. PMID- 2319805 TI - Dexamethasone decreases membrane fluidity of leukemia cells. AB - Lipid fluidity in the plasma membrane of leukemia cells was determined by measuring steady-state fluorescence polarization (P) of 1,6-diphenyl-1,3,5 hexatriene. In vitro dexamethasone treatment induced a dose-, time- and temperature-dependent and reversible increase in P values of primary leukemia cells and glucocorticoid-sensitive leukemia cell lines having specific glucocorticoid receptors. Membrane fluidity of glucocorticoid-resistant subclones with impaired specific dexamethasone binding capacity was not influenced by the drug. The results of this study suggest that dexamethasone modulates leukemia cell membrane fluidity via a classical glucocorticoid receptor dependent pathway. PMID- 2319806 TI - Prognostic factors of myelodysplastic syndromes--a simplified 3-D scoring system. AB - From 1 January 1982 to 31 December 1986 in five haematological centers of the west of France (Rennes, Rouen, Nantes, Tours and Angers), we have collected 503 cases of myelodysplastic syndrome (MDS). These cases were classified by FAB recommendation as followed: 85 refractory anemia with ring sideroblasts (RARS); 273 refractory anemia in which 86 were without blasts (RA), 153 were with excess of blasts (RAEB) and 34 were with excess of blasts and in transformation (RAEB t); 111 chronic myelomonocytic leukaemia (CMML); and 34 cases with borderline features. The point date for statistical study was 31 December 1988, and the scoring method of Bournemouth was applied to compare with our findings (62% resulted in death, 18% in leukemic transformation). It was demonstrated that haemoglobin, platelets, and bone marrow-blasts are the best factors to predict survival or leukaemic transformation (LT). But peripheral neutrophils don't affect the survival time excepted when lower than 500 microliters (13 months vs 19.6 months). A scoring system based on haemoglobin (Hb), platelets (Pl), and bone marrow blasts (BMB) may be represented in a three-dimensional space and is a good tool to know the own value of each parameter. This 3-D system shows that BMB and Pl are the most important factors and are correlated with survival, per cent of death, and LT (p less than 0.0001). The LT is observed in 18% of the whole population. RAEB and RAEB-t progress in AML2 (14.6%) or AML4 (1.4%), and CMML progress in AML2 (8.1%) or AML4 (11.7%). We observed that monocytes are not good parameters to predict the type of leukemic transformation. Furthermore, survival of RA treated with Ara-C(ld) or not treated was similar. PMID- 2319807 TI - Human B lymphocytes express the p75 component of the interleukin 2 receptor. AB - The nature of the interleukin 2 (IL-2) receptor on purified human B lymphocytes was examined. Both normal and malignant cells showed evidence of a 70-75,000 mol. wt (p75) IL-2 binding molecule as assessed by 125I-labeled IL-2 binding and receptor cross-linking. On normal, Tac-negative B lymphocytes the estimated number of p75 binding sites was 1100 per cell and the dissociation constant (Kd) was 1.7 nM. Consistent with this, cross-linking experiments demonstrated the presence of an IL-2 binding molecule of 70-75,000 mol. wt. Purified B cells from patients with hairy cell leukemia and chronic lymphocytic leukemia (CLL) also expressed the p75 IL-2 binding molecule. In the HCL samples, a small number of high-affinity IL-2 binding sites were detected (27-90) while the majority of binding sites (2100-10,800) were typical of low-affinity p55 Tac binding. IL-2 added to the purified normal and CLL B lymphocytes led to the induction of p55 Tac expression and the generation of high-affinity IL-2 receptors. This response to IL-2 was equivalent to the response observed when normal B lymphocytes were stimulated by Staphylococcus aureus Cowan I. PMID- 2319808 TI - Proliferation and differentiation of erythroleukemia cell line (ELM-I-1) in response to erythropoietin and interleukin 3. AB - Here we describe the characterization of Epo-responsive mouse erythroleukemia cell line ELM-I-1. ELM-I-1 cells possess Epo binding sites on their membranes and differentiate into hemoglobin-positive cells when cultured in the presence of Epo. About 20% of the cells were hemoglobin-positive after a 3- to 4-day exposure to recombinant human Epo in liquid culture. Supplementation of recombinant mouse IL-3 during culture had an augmentative effect on Epo-mediated differentiation, although IL-3 alone did not induce differentiation. Both Epo and IL-3 stimulated the growth of ELM-I-1 cells, and their effects were a slightly additive. These findings indicate that ELM-I-1 cells are suitable for studying the interaction between Epo and IL-3 in erythroid differentiation at a subcellular level. ELM-I-1 may also offer a valuable bioassay system for Epo. PMID- 2319809 TI - Changes in leukemia cell membrane fluidity induced by growth-restrictive and permissive culture conditions. PMID- 2319810 TI - Beam-walking in rats: studies towards developing an animal model of functional recovery after brain injury. AB - While it has long been recognized that humans recover function after stroke or head injury, the direct impact of drugs on recovery has only recently received attention. The ability of rats to traverse a narrow, elevated beam has proven to be particularly useful when studying the effects of pharmacologic manipulations on motor recovery following cortical injury. However, the effect of testing conditions on the recovery of beam-walking performance has not been investigated. Treatment with amphetamine facilitated recovery of beam-walking following cortical lesions regardless of whether 'massed' or 'spaced' trials were employed. Unexpectedly, the performance of sham-operated controls declined when tested with 'massed' trials. 'Prodding' sham-operated rats by tapping on the rump abolished this decline in performance, but resulted in enhanced recovery in lesioned animals. The results indicate that testing conditions can exert a significant influence on beam-walking performance and are important to consider when interpreting the impact of pharmacologic agents on the recovery process. PMID- 2319811 TI - Automatic classification and analysis of microneurographic spike data using a PC/AT. AB - Using a standard PC-AT with a commercial analog data interface a system was designed which supports microneurographic experiments and which may also be used for other types of extracellular spike recordings. The signal is sampled on-line at 25 kHz and a spike is detected if the signal passes a certain threshold. The spikes are displayed on the screen and stored on disk. A second on-line mode records the responses of the examined unit to electrical stimulations, which are used to identify the type of fibre and to test the subsequent spike classification. The spikes are classified off-line using a template matching algorithm, which has unsupervised learning and discrimination phases. The results are displayed in a time-frequency plot and may be checked with the responses to electrical stimulations. Artifacts from EMG and other electrical fields are reliably sorted out. In recordings, which include more than one unit, their spikes are discriminated with a low error rate. PMID- 2319812 TI - Computer programs for the analysis of immunohistochemically labeled spinal cord sections. AB - A microcomputer based image processing system has been developed to analyze the density of immunohistochemical labeling within neural tissue. The system permits the tracing of anatomical regions seen on a digitized image and the determination of the area and the mean gray level of all pixels lying within each defined region. Corrections are made for uneven screen illumination and for nonlinearity of the video camera's response to gradations in optical density. A standardization procedure ensures that the same level of incident illumination is used during each experiment. An example of an application of this system is described in which unilateral changes in immunohistochemical staining density were determined within the rodent spinal cord following partial spinal injury. This system provides a sensitive and objective means of analyzing such changes. PMID- 2319813 TI - D-tartrate alters uptake of [3H]dopamine into brain synaptic vesicles. AB - The use of D-tartrate containing media for measuring uptake of catecholamines into brain synaptic vesicles alters the properties of transport. Absolute concentrations of inhibitors determined in competition studies should be viewed with caution. PMID- 2319814 TI - Development of a computer program classifying rat sleep stages. AB - We developed a simple and precise program for the on-line judgement of the sleep stages of four rats simultaneously for an unlimited period, using a commercially available general purpose signal processor (NEC-Sanei 7T17; 32-bit, 5 MHz, 4 Mbyte, 1 Mbyte 1 floppy disc drive). EEG and EMG were recorded with an 8-channel polygraph (NEC-Sanei, System 380) through electrodes chronically implanted into the brain. The signals were A/D converted every ms and integrated for 2760 ms after full-wave rectification, and the subsequent 2240 ms was used for calculation and further analysis. All data were handled with this 5000 ms as the minimum unit. Then 3 sleep stages, i.e., waking, slow-wave sleep, and REM sleep, were determined by a template matching method from the relative amplitudes and durations of the integrated EEG, EMG and EMG surge data based on algorithms of standard visual amplitude analysis criteria for the sleep-stage classification. An agreement matrix was constructed between the data scored by the visual and by the automatic analysis, and the agreement value was satisfactory, although slight variability was seen in the REM sleep-stage determination. This result indicated that EEG and EMG data analysis is appropriate for researching the circadian rhythmic mechanism of the sleep-wake cycle. PMID- 2319815 TI - Operant conditioning of H-reflex in freely moving monkeys. AB - The H-reflex, the electrical analog of the stretch reflex or tendon jerk, is the simplest behavior of the primate CNS. It is subserved by a wholly spinal two neuron reflex arc. Recent studies show that this reflex can be increased or decreased by operant conditioning, and that such conditioning causes plastic changes in the spinal cord itself. Thus, H-reflex conditioning provides a powerful new model for investigating primate memory traces. The key feature of this model, the conditioning task, originally required animal restraint. This report describes a new tether-based design that allows H-reflex measurement and conditioning without restraint. This design integrates the conditioning task into the life of the freely moving animal. PMID- 2319816 TI - Image analysis of CNS neurotrophic factor effects on neuronal survival and neurite outgrowth. AB - We have developed a method for quantifying the effects of neurotrophic factors by using digital image processing techniques to enhance the morphometric analysis of cultured neurons. Dissociated cell cultures from rat embryonic cerebral cortex were selected as a model biological system. Binary images of neuronal neurites were extracted from gray images of cultured neurons stained with Coomassie brilliant blue. Pattern recognition techniques were used to estimate the number of neurons per culture dish and the average length of the neurites on each cell. In 4-day cultures, addition of extracts from 2-week-old rat cortices dose dependently increased both parameters. The method proved suitable for use in bioassays of factors influencing neuronal survival and neurite promotion. PMID- 2319817 TI - Long term recordings in the cat motor cortex: unit activity and field potentials from sensory and brain stem stimulation as a means of identifying electrode position. AB - A method of chronically implanting microwires (25 microns diameter, 90% Pt/10% Ir wire) in the cat pericruciate cortex is described. These wires can obtain simultaneous recordings of single and multiunit activity from different sites and multiple recordings from the same site on different postoperative days. The electrodes were permanently implanted in the anaesthetized animal and left in place. Recordings were carried out in the awake, unrestrained cat. Different units were recorded as a result of spontaneous electrode movement in the cortex. Movement was documented with field potential recording from the implanted electrodes and resulted in changes in the latency and polarity of the initial components of the cutaneous field potential and changes in the number of components of the field potential elicited from brain stem stimulation. Changes in the receptive fields of the units, changes in the number of units antidromically invaded from brain stem stimulation, and in the threshold and occurrence of muscle activity elicited from intracortical microstimulation supported the evidence of electrode movement obtained from field potential recordings and could be used to document electrode movements tangential to the plane of the cortical laminae. Movement was a slow gradual process throughout the period of implantation. The longest period from which a single unit could be recorded was 2 days. The need for this neurophysiological analysis is supported by evidence for irregular electrode movement which could not have been reconstructed from histological examination of the cortex. PMID- 2319819 TI - RCN launches nationwide return to nursing project. PMID- 2319818 TI - A pipette holder for use in patch-clamp measurements. AB - A novel design for a pipette holder for use in patch-clamp experiments is presented. The holder is designed for use in patch-clamp amplifiers equipped with female BNC-type connectors on the headstage. In this design the glass micropipette cannot contact the Ag/AgCl electrode, thus avoiding deterioration and subsequent offset voltages and baseline current drifts of the Ag/AgCl electrode, induced by frequent replacement of micropipettes. PMID- 2319820 TI - Pathways to psychotropic drugs. Understanding the basis of gender differences. AB - Earlier studies have established substantial gender differences in the likelihood of obtaining a psychotropic drug prescription, and a correlation, especially among women, with such family characteristics as family responsibilities, marital separation, divorce or widowhood, and the presence of family stressors such as an ill spouse. However, the pathways to psychotropic drug use are not clearly understood. Data from the National Medical Care Expenditure Survey show that gender differences in obtaining a psychotropic drug can be accounted for by the greater likelihood of women to perceive illness, particularly mental illness and musculoskeletal conditions, diagnostic conditions that together account for roughly half of all psychotropic drug prescriptions. In relation to family responsibilities, employment significantly decreases the likelihood of a psychotropic drug prescription for both men and women. The greater likelihood of divorced, separated, or widowed women to obtain psychotropic drugs can be explained by their greater likelihood of episodes of illness, particularly those involving mental illness, and by their greater number of physician visits. The presence of all ill spouse is associated with psychotropic drug use only indirectly by increasing the likelihood of Medicaid coverage. Thus, differences between men and women in the likelihood of obtaining prescriptions for psychotropic drugs do not appear to result from different physician-patient interactions or from gender-determined treatment norms by physicians. PMID- 2319821 TI - A community survey of self-medication activities. AB - The objectives of this research were to explore lay medication activities as an aspect of self-managed health care in the Canadian context and to identify the sociodemographic and sociomedical characteristics of those who engage in self medication. Interview data were collected in 1983 from a random cross-sectional sample of 524 adult residents living in Winnipeg, Canada. Respondents were questioned about the types of medicines they keep in their home (both prescribed and nonprescribed), self-treated symptomatic conditions; recent medication activities, the use of prescribed medicine in self-treated illness episodes, and the use of home remedies. This study contributes to a growing body of international evidence that has demonstrated that self-medication is a vital part of daily self-care behavior. For the most part, the results are comparable to those reported by previous British and U.S. studies of self-medication. Winnipeg residents were found to be active self-care providers who engage in a variety of self-medication practices. The study also illustrates the fact that the altered use of prescribed drugs (particularly by those with higher levels of formal education) is an important aspect of self-medication behavior. These findings have clear implications for health care practitioners. PMID- 2319822 TI - Explaining variability of cost using a severity-of-illness measure for ICU patients. AB - Factors related to hospital resource use by intensive care unit (ICU) patients, including severity of illness at admission and intensity of therapy during the first 24 ICU hours were explored in this study. Analysis was based on 2,749 patients admitted to the general medical-surgical ICU at Baystate Medical Center, Springfield, Massachusetts, between February 1, 1983 and January 10, 1985. Resource use was indexed by hospital length of stay (LOS) adjusted for differences between ICU and other hospital days. Severity of illness was measured by the Mortality Prediction Model (MPM0), a validated predictor of outcome but not previously used to analyze resource consumption. Intensity of therapy was measured using the Therapeutic Intervention Scoring System (TISS). The 10% of patients with longest ICU stays were significantly different from the other 90% with respect to previous ICU use, MPM probability, and TISS score. Variability in resource use was analyzed using four diagnosis-related groups (DRGs) accounting for large numbers of ICU patients. The relationship between severity of illness and resource was nonlinear: as severity increased from low levels, resource use increased at a decreasing rate, reached a plateau, and eventually declined. Within each DRG, MPM0 explained a statistically significant percentage of the variability in resource use. PMID- 2319823 TI - Using relative productivity assessments for allocating housestaff to departments. PMID- 2319824 TI - Treatment of patients with asthma by specialists and generalists. PMID- 2319825 TI - Environmental medicine: introduction and overview. AB - Human health and longevity have long been known to depend on a complex interplay between hereditary and nonhereditary determinants. The latter include various lifestyle factors, as well as physical and chemical agents encountered in air, food, water, consumer products, the workplace, and the environment at large. Knowledge of these determinants is becoming increasingly important to the physician and other members of society in the maintenance of human health and in the diagnosis and treatment of the diseases of modern life. PMID- 2319826 TI - Environmental medicine. PMID- 2319827 TI - Role of the physician in environmental medicine. AB - This article describes the role of the medical history and of laboratory findings in diagnosing diseases caused by environmental chemicals. An understanding of routes of exposure is crucial in appropriate diagnosis and in preventing further harm. A listing of potential sources of information is also included. PMID- 2319828 TI - Environmental causes of cancer. AB - The development of cancer in an individual is the result of multiple genetic and epigenetic steps. Carcinogens and tumor promoters can act by a variety of molecular mechanisms, and repeated exposure to numerous agents is frequently necessary for the formation of cancer. The estimate of cancer risk in a population is performed via a formal quantitative risk assessment. The estimated risk in an individual is more complex because of both inherited predispositions and lifestyle. Although information is available, it is essential to understand the goals, attributes, and limitations of the experimental methods underlying our current understanding of the environmental causes of cancer. PMID- 2319829 TI - Environmentally related disorders of the cardiovascular system. AB - The patient's level of activity is typically the only work-related concern considered in clinical medicine. This article discusses why it is important for clinicians to expand their concern to include the possibility of exposure to various gases, metals, and chemicals when evaluating a patient with cardiovascular disease. Both at the time of diagnosis and when deciding whether a patient can return to work, the workplace exposures need to be reviewed for their potential to exacerbate or cause cardiac symptoms or even death. An appropriate exposure history with confirmatory laboratory tests will allow the clinician to diagnose and manage environmentally related cardiovascular disease. PMID- 2319830 TI - Disease-causing effects of environmental chemicals. AB - Both toxicologic studies and studies in environmental chemistry are important in assessing the potential adverse health effects of human exposures to hazardous environmental agents. This article discusses the toxic effects of chemical concentration at the target organ or site and how the concentration is related to the level of external exposure. PMID- 2319831 TI - Health effects of ionizing radiation. AB - Although humans have evolved in an environment of ionizing radiation, it was not until man-made sources were developed that the effects of ionizing radiation started to become known. Detection and measurement of radiation is not only sophisticated but widely applied. This article deals with exposure to this kind of radiation and the risk it may cause. PMID- 2319832 TI - Relationship between the effect of cyclophosphamide on adjuvant arthritis severity, skin allograft rejection and spleen cell cytotoxic activity in rats. AB - Cyclophosphamide, which has a poor immunosuppressive effect on adjuvant arthritis in rats, evokes an aggravating form of the disease when applied at a single low dose before rats' sensitization with complete Freund's adjuvant. However, cyclophosphamide administered by this method of treatment has no such enhancement effect on skin allograft rejection reaction; on the contrary, the rejection reaction was inhibited. Spleen cell cytotoxic activity against 51-Cr labelled chondrocytes significantly decreased in adjuvant arthritis, while in skin allograft rejection it increased during the latent period before the rejection reaction appeared. The addition of cyclophosphamide to the rats' treatment decreased more strongly spleen cell cytotoxic activity, especially in rats with adjuvant arthritis. We conclude that cyclophosphamide-sensitive spleen cytotoxic cells are playing a dual role in the pathogenesis of these two cell-mediated immunological processes: as immunosuppressive regulatory cells in adjuvant arthritis and as effector cells in skin allograft rejection reaction. PMID- 2319833 TI - Inductive effects of rifapentine on mice hepatic mixed function oxidase system. AB - Rifapentine (R773, DL473) is a long-acting antituberculous drug used in China. In our experiments we have found some manifestations of induction of hepatic mixed function oxidase system in mice following pretreatment with rifapentine or phenobarbital. Both rifapentine and phenobarbital significantly increased the rate of antipyrine and pentobarbital metabolism in vivo. They also increased liver weight, the content of liver microsomal protein and cytochrome P-450, the activity of NADPH-cytochrome C reductase and NADPH oxidase. SDS-polyacylamide gel electrophoresis showed that the relative proportions of some polypeptide bands in mice microsomal fraction were significantly changed following rifapentine or phenobarbital pretreatment. The results indicate that rifapentine, like phenobarbital, is a potent inducer of hepatic mixed function oxidase system in mice and that it should be used carefully in clinical therapy, when combined with other drugs. PMID- 2319834 TI - Effect of experimental hyperthyroidism on atropine pharmacokinetics in sheep. AB - Atropine sulfate (0.02 mg/kg, i.m.) was administered to normal sheep and to sheep with experimentally induced hyperthyroidism. Serum and urine concentrations of atropine measured by radioimmunoassay were monitored over an 8-h period. The time to reach maximum serum concentration was similar in both hyperthyroid and normal sheep. A comparison between normal and hyperthyroid sheep indicated that the atropine absorption rate was not changed, but its rate of elimination was significantly greater in hyperthyroid sheep (p less than 0.01). Hyperthyroidism resulted in significant decreases in atropine (p less than 0.05), MRT (p less than 0.01), AUC (p less than 0.01) and an increase in C1/F (p less than 0.01) when compared to atropine kinetics of normal sheep. PMID- 2319835 TI - In vivo distribution of hydrocortisone over whole blood: a novel method for the extraction of erythrocytes. AB - Ten mg hydrocortisone (HC) was administered intravenously to a healthy volunteer after a dexamethasone suppression test and HC concentrations were determined from 1-270 min in plasma, plasma water and on erythrocytes. HC was extracted from erythrocyte concentrates with high efficiency by HC-poor plasma or by human or bovine albumin solutions. Determination of HC in the plasma of the volunteer mainly gave insight about the concentration time course of HC bound to plasma proteins. One minute after HC injection the amount associated with erythrocytes was about half the amount bound to plasma proteins. Decrease of HC in plasma, and hence on plasma proteins, was monophasic from 30-270 min with a half-life of 116 min. Decrease of HC associated with erythrocytes and HC free in plasma water was biphasic from 30-270 min and initially HC diminished about five times faster from these compartments than from plasma proteins. At the end of the observation period half-lives on plasma proteins, erythrocytes and in plasma water were similar, i.e., at 120 min. It is concluded from these as well as from previous in vitro experiments that erythrocytes gain importance as HC carriers at increasing HC blood concentrations. Once charged, erythrocytes yield HC much more readily than do plasma proteins. This "last come first go" phenomenon of association of HC with erythrocytes is known also to exist for certain drugs. It indicates erythrocytes as important transporters of non-freely in water soluble compounds. PMID- 2319836 TI - Improvement of peroral absorption of cyclosporine A by microemulsions. AB - The rat was found to be a suitable model for pharmacokinetic and bioavailability studies of cyclosporine A (CsA). All pharmacokinetic parameters studied were in the same order of magnitude as those found in man. Two peroral formulations in the form of microemulsions were compared with a commercially available P.O. solution (to be diluted for administration) and a solution for intravenous administration. Of the two microemulsions, one resulted in an extent of absolute and relative bioavailability significantly higher than that of the available P.O. solution. Biliary recycling was observed upon all routes of administration. If uncorrected for biliary recycling, both absolute and relative bioavailability are overestimated. PMID- 2319837 TI - The measurement of propofol in human blood samples by liquid chromatography. AB - A simple, sensitive, reliable and rapid column liquid chromatographic method was developed for the measurement of propofol, a new anesthetic agent, in human maternal and placental blood. The assay involved a single extraction of the drug and internal standard, thymol, from blood buffered with 0.1 M sodium dihydrogen phosphate buffer into cyclohexane. The organic extract, basified with tetramethylammonium hydroxide, in evaporation tube was evaporated to dryness at 30 degrees C under nitrogen. The residue was redissolved in 80 microliters acetonitrile and an aliquot (25-50 microliters) of the concentrate was injected into a C18 reversed-phase column (4 microns, Nova-Pak) linked to a C18 pre column. The mobile phase consisted of 60% (v/v) acetonitrile in distilled water containing 1% v/v glacial acetic acid and was eluted at 2.5 ml min-1. The components of the column effluent was monitored by a fluorometric detector with excitation and emission wavelengths set at 276 nm and 310 nm, respectively. The method has been used to measure propofol concentrations in blood from maternal veins and placental arteries and veins during cesarean section. PMID- 2319838 TI - Pharmaco-toxicological effects of acetaminophen in rodents. Battery of tests to screen potential analgesic acetaminophen derivatives. AB - The pharmacological effects of acute oral administration of acetaminophen have been extensively evaluated in rodents. Using this drug as reference compound we have also standardized several pharmaco-toxociological tests in order to select new analgesic-antipyretic acetaminophen derivatives. According to the results obtained in this work, the following battery of assays is proposed to screen these compounds: a) pharmacological: antipyretic activity against Brewer's yeast induced pyresis in rats; analgesic activity against chemical-induced writhings in mice and paw pressure test in rats; b) toxicological: oral acute toxicity in mice with and without phenobarbital pretreatment; determination of SGOT and SGPT activities as well as total bilirubin in mice. The usefulness of this procedure in the evaluation of drug effects is also considered. PMID- 2319839 TI - A rapid embedding procedure for the study of platelet interactions with extracellular matrices in a flowing system. Effect of aspirin on platelet activity. AB - The cultured endothelial cell (EC) is currently used as a model for the study of the interaction of platelets with the vascular wall. Described is a method for rapid quantitative and qualitative evaluation of platelet interactions with extracellular matrices (ECM) produced by human cultured ECs growing on plastic coverslips. Morphometric calculations can be performed on the same perfused coverslips. A very good correlation (r = 0.96) was found between results of a morphometric method en face and those obtained from analysis of cross sections of the perfused coverslips. A shear rate-dependent increase on platelet deposition onto ECMs was observed with both morphometric procedures. The method is sensitive enough to detect drug-related changes of platelet function. An impairment of the interaction of platelets with the ECM was observed when blood obtained from healthy volunteers who took 500 mg aspirin/day for five days was perfused. Aspirin showed a marked effect, decreasing platelet spreading onto the subendothelium (p less than 0.05). The embedding method described benefits from the use of plastic coverslips that are easily detected from the glycol methacrylate compound used for the embedding procedure. Quantitative analysis en face (covered surface) and qualitative evaluation of platelet interactions (contact, adhesive and aggregated platelets) in cross sections are performed on the same coverslip. This embedding procedure provides a useful tool for the study not only of platelet interactions with ECMs but also for the investigation of interactions of blood elements with other cultured cells. PMID- 2319840 TI - New methods to detect the effect of alteration in gastric pH and intestinal transit by metoclopramide and propantheline using a continuous gastric pH probe and hydrogen breath analysis. AB - The effects of oral doses of metoclopramide (M, 10 mg) and propantheline (P, 30 mg) on alteration in gastric pH and emptying were determined using a continuous pH probe (Digitrapper, Synectics) and hydrogen breath analysis (HBA, QuinTron) in eight male subjects. The four phases consisted of HBA, HBA and pH probe, and HBA and pH probe and either P or M. Baseline pH measurements were recorded for 60 min prior to dosing with 10 g of lactulose in three of the periods. Dosing with P or M was given 30 min before administration of lactulose. HBA and continuous gastric pH were measured for 120 min. M produced earlier and higher peak hydrogen concentration than control (p less than 0.0001). P decreased peak hydrogen and increased gastric pH from approximately 2.0 to 4.0 (p less than 0.0001). CONCLUSIONS: 1) HBA can be used to detect alterations of intestinal motility; 2) The gastric pH probe produces a small increase in intestinal motility; and 3) The combination of the gastric pH probe and HBA could be a useful technique to simultaneously evaluate gastric pH and gastrointestinal motility. PMID- 2319841 TI - In vitro effect of cilazaprilat on sodium-potassium transport systems in human erythrocytes. AB - The in vitro effects of cilazaprilat in a concentration range of 10 nM to 1 mM were investigated on various Na+ and K+ transport systems in human red blood cells. Cilazaprilat inhibited the anion carrier or DIDS-sensitive LiCO3(-)-influx and the bumetanide-sensitive K(+)-efflux. However, no effect of cilazaprilat on the Na+, K(+)-pump activity, the number of active Na+ pump units and on the Na+, Li(+)-countertransport activity could be demonstrated. It is suggested that through a decreased anion carrier indicating a decreased Na(+)-influx, the lower intracellular Na+ concentration observed in vivo during angiotensin-converting enzyme inhibition, can be at least partly explained. PMID- 2319842 TI - Early afterdepolarization in mouse atrial fibers induced by 3.0 mM K+ and the inhibitory effects of tetrodotoxin and nifedipine. AB - Early afterdepolarization (EAD) was induced under superfusion of Tyrode solution (K+ = 3.0 mM) at a longer cycle length in mouse atrial fibers. The relationships between the duration and the number of triggered bursts and cycle length were exponential (n = 17). Thus, EAD possesses the property of cycle length dependence. Under a moderate concentration of TTX (4.0 microM) or nifedipine (5.0 microM) treatment, EAD was partially inhibited but maintained cycle length dependence. When a high concentration of the drugs (30 microM and 8.0 microM, respectively) was applied, EAD was abolished at all cycle lengths of driving stimulation. It is suggested that both inward currents (INa and ICa) are involved in the generation of EAD in mouse atrial fibers. PMID- 2319843 TI - [Konzo--a new motor neuron disease--a challenge for public health work and basic research]. PMID- 2319844 TI - [The triple cuff. The ambition of the scientist/physician must be to give correct information]. PMID- 2319845 TI - [HIV testing of adopted children--how long?]. PMID- 2319846 TI - [Treatment in the climacteric. Large or small gestagen dominance?]. PMID- 2319847 TI - [There is no reason to centralize hypophysectomy]. PMID- 2319848 TI - [A Salmonella epidemic costs 583 days of health insurance and compensation of the carrier of the infection]. PMID- 2319849 TI - [Children adopted from abroad are often Salmonella carriers for a long time]. PMID- 2319850 TI - [Dilated cardiomyopathy and tachycardia--cause and effect?]. PMID- 2319851 TI - [Unclear lung disease was cor triatriatum with late onset of symptoms]. PMID- 2319852 TI - [Why always use a P for significant results?]. PMID- 2319853 TI - [Concerned ethics--to prevent manipulation, moralizing and short-sightedness in health education]. PMID- 2319854 TI - [The scientific basis of general medicine. Increased importance of qualitative research]. PMID- 2319855 TI - [How are local health data used?]. PMID- 2319856 TI - [Are children facing a better future?]. PMID- 2319857 TI - [The kangaroo method. A medical ambivalence towards nature?]. PMID- 2319858 TI - [Protection against blows must be put in the boxers' gloves!]. PMID- 2319859 TI - [Ambulatory myelography is cheaper]. PMID- 2319861 TI - [The triple cuff. The importance of information about commercial product]. PMID- 2319860 TI - [Is biopsy necessary in cytologically proven breast cancer?]. PMID- 2319862 TI - [A new type of compression stocking is more effective in deep venous insufficiency]. PMID- 2319863 TI - [An implantable defibrillator saves lives in ventricular arrhythmia]. PMID- 2319864 TI - [Perimyocarditis and Addison's crisis--a case of acute cardio-endocrinology]. PMID- 2319865 TI - [Cesarean section rate is decreasing in Sweden]. PMID- 2319866 TI - [Are physicians responsible for the environment?]. PMID- 2319867 TI - [Vaccination against influenza--a purposeful activity?]. PMID- 2319868 TI - [Contraception counseling. Cooperation between physicians and midwives is valuable even in the future]. PMID- 2319869 TI - [Investigation of occult hyperkalemia. Even potassium determination in heparinated plasma should be included]. PMID- 2319870 TI - [Kallikrein in urine is an early marker of hypertension]. PMID- 2319871 TI - [Fixed routines of Balint's movement demand innovation and research]. PMID- 2319872 TI - [Who visits the district nurses in Gothenburg?]. AB - All visits to or by the district nurses in Gothenburg, Sweden, were registered during one week (daytime Monday to Friday). Altogether 5,250 visits were registered. 77 per cent of all visits concerned subjects 65 years of age or older and 54 per cent subjects 75 years of age or older. It was more common for a woman to visit or be visited by a district nurse than for a man. Of the visits 70 per cent were made by the nurses (59 per cent to the homes of the patients and 11 per cent to homes for the aged), while 30 per cent of all visits were made by the patients to the district nurse's office. Very few visits concerned foreigners living in Sweden. Visits to or by old people were slightly more time-consuming than those to or by younger patients. When planning resources for visits to or by the district nurses it seems that age is by far the most important factor to take into consideration. PMID- 2319873 TI - [4 siblings with Bartter's syndrome]. PMID- 2319874 TI - [A well-functioning resuscitation chain can save lives in near-drowning]. PMID- 2319875 TI - [Pneumothorax and pulse oximetry]. PMID- 2319876 TI - [Preparatory public high school for schizophrenics. A modified curriculum provides quiet working environment and security]. PMID- 2319877 TI - [The ethics of clinical training--must patients cooperate?]. PMID- 2319878 TI - [The doctor, mass media and intelligibility. Why are physicians not learning more about the pharmacokinetics and dynamics of the language?]. PMID- 2319879 TI - [Research on maternal mortality in developing countries--a global priority]. PMID- 2319880 TI - Effects of short-term endotracheal intubation on vocal function. AB - Transient voice change associated with endotracheal intubation has generally been attributed to vocal fold trauma. To assess the role of altered vocal fold function in transient voice change, a study was designed to evaluate the audioacoustic, endoscopic, and laryngostroboscopic characteristics of the postintubation voice. Vocal function of 10 patients undergoing short-term outpatient surgical procedures using general anesthesia and endotracheal intubation were studied preoperatively and postoperatively. A second group of 10 patients that did not have surgery or general anesthesia was used as an age matched control. Fundamental frequency, frequency perturbation, electroglottography, endoscopy (including laryngeal stroboscopy), and subjective speech analysis by experienced listeners were used to assess vocal function. No consistent differences in fundamental frequency were observed, although patient to-patient variation was marked. Statistically significant increases in cycle-to cycle fundamental frequency variation (jitter) were found postoperatively in the majority of the postintubation patients (P less than 0.05). Electroglottography, laryngeal endoscopy, and stroboscopic laryngoscopy did not demonstrate consistent changes in glottic mucosal function. Listener judgments characterized the postintubation voice change by decreased intensity, increased roughness, and lowered affect without consistent changes in pitch. The perception of decreased affect in the voices (characterized by reduction in pitch variation, vocal stress, and increases in pause times) was a strong perceptual marker for change in the post-intubation voice. Objective measures of laryngeal function suggest that the glottic contribution to postintubation voice change is minimal and that this dysphonia is probably multifactorial. PMID- 2319881 TI - Unusual presentations of lymphoma of the head and neck in childhood. AB - Lymphoma of the head and neck in children can pose a significant diagnostic problem, especially when histologic analysis indicates non-Hodgkin's lymphoma and the initial site of involvement is extranodal. This report describes 15 pediatric cases of lymphoma seen from 1981 to 1987 with an initial presentation in the head and neck. Cervical lymph nodes represented the initial site of involvement in 10 of the cases. The other five cases presented with disease in the tonsillar fossa; maxillary sinus and mandible; parotid; pharyngeal wall; trachea and thyroid gland; and ethmoid sinus, sphenoid sinus, and anterior fossa. The histologic type was non-Hodgkin's lymphoma in 12 cases and Hodgkin's lymphoma in 3 cases. Our experience has shown that lymphoma of the head and neck in children presents a confusing clinical picture and was initially confused with inflammatory disease, polymorphic reticulosis, and other neoplasms such as rhabdomyosarcoma. In one patient, Epstein-Barr virus infection and an inherited immunodeficiency state probably played a role in the pathogenesis of the lymphoma. PMID- 2319882 TI - Intranasal and transantral ethmoidectomy: a 20-year experience. AB - Ethmoidectomy is an operation that has engendered controversy concerning the best route of surgical access. The purpose of this study was to present the results of the authors' experience in more than 1300 intranasal sphenoethmoidectomies and transantral sphenoethmoidectomies performed over a 20-year period. The authors contend that the most effective ethmoidectomy is the most complete ethmoidectomy and have previously presented a case for ethmoid marsupialization. Polyp recurrence rates of less than 20% and a major complication rate of less than 1% were reported in this study. PMID- 2319883 TI - Severe versus profound sensorineural hearing loss in children: implications for cochlear implantation. AB - The advent of cochlear implants for children has stimulated interest in the specific sensory deficits and communicative capabilities of children with severe or profound bilateral sensorineural hearing loss. Appropriate management of these children and their families requires an appreciation of the multifaceted developmental and educational challenges confronting deaf children, even after cochlear implantation. Evaluation results from 200 children with bilateral sensorineural deafness (63 severe/137 profound, anacusic, and fragmentary) reveal significant differences between these two subpopulations. Within the profoundly impaired group, important differences were also noted in the children's ability to benefit from conventional amplification, depending on residual hearing at or above 1000 Hz. Strategies for assessing auditory function and aided benefit in severely and profoundly hearing-impaired children must involve a pediatric test battery, serial evaluations, and parental cooperation/support. When selecting candidates for cochlear implantation, it is inappropriate to categorize severely hearing-impaired children with those children having profound sensorineural losses. Even profoundly impaired populations are not homogeneous, and rehabilitation potential with conventional amplification must be determined on an individual basis, over time. PMID- 2319884 TI - The effect of cosmetic rhinoplasty on nasal patency. AB - Fifty patients who primarily desired cosmetic improvement underwent nasal airflow studies using posterior rhinomanometry before and after reduction rhinoplasty. There was no significant difference in nasal resistance before and after surgery. This study demonstrates that neither subjective nor objective nasal obstruction follows reduction rhinoplasty, despite the potential for a decreased cross sectional area of the valve region. PMID- 2319885 TI - Acquired airway obstruction from histologically normal, abnormally mobile supraglottic soft tissues. AB - In patients with nonmalignant upper aerodigestive tract abnormalities such as cysts, neoplasms, and laryngomalacia, airway obstruction has been described as a function of not only size and location of abnormal structures, but also of their mobility. This paper describes three patients who developed upper airway restriction with stridor due to abnormally redundant and mobile, but histologically normal, supraglottic mucosa. The specific mechanism of and structures involved in obstruction were clearly defined by videolaryngopharyngoscopy. Endoscopic microdissection and/or laser excision of the redundant supraglottic mucosa restored airway patency and completely relieved the obstructive respiratory symptoms. The pulsion effects of inspiratory airflow are postulated as the cause of these acquired lesions. Recommended treatment is reviewed. PMID- 2319886 TI - An autosomal dominant inherited syndrome with congenital stapes ankylosis. AB - A newly recognized autosomal dominant inherited syndrome associated with congenital conductive deafness, hyperopia, broad thumbs, broad first toes, short distal phalanges, and syndactyly is reported. The conductive loss was the result of congenital stapes ankylosis and, in two cases, was associated with ankylosis of the short process of the incus in the fossa incudis. Stapedectomy improved hearing in these patients. Fused cervical vertebrate are also an associated feature. PMID- 2319887 TI - KTP-532 laser tonsillectomy: a comparison with standard technique. AB - It has been stated that laser excision of oral and oropharyngeal lesions result in less intraoperative blood loss, reduced postoperative pain, and quicker wound healing, but few controlled studies have been done to substantiate these claims. A study was undertaken to examine the benefits of the KTP-532 laser in a group of 31 patients who underwent tonsillectomy. One tonsil was removed with the KTP-532 laser and the other was excised with conventional dissection and snare technique. Patients were not told which tonsil was removed with the laser. Pain, healing, and intraoperative blood loss comparing one side to the other was assessed. On the evening of surgery, 83% of patients selected the side that underwent standard dissection and snare tonsillectomy as the most painful. By midweek, however, approximately equal numbers of patients selected the laser side as the most painful. At the end of 1 week, 63% of patients felt more pain on the laser dissection side. Possible reasons for these results are discussed. Intraoperative blood loss was significantly reduced with the use of the KTP-532 laser, but healing was not accelerated. PMID- 2319888 TI - Early alterations of cochlear function in experimental perilymph fistulas. AB - Alterations of cochlear function secondary to perforation of the round window membrane in guinea pigs were expected to reveal sensitive and/or specific audiometric parameters in perilymph fistulas. A perforation of the round window membrane either did not affect acoustic compound action potential thresholds, or induced a delayed, possibly conductive, inner ear hearing loss. Also, evoked suprathreshold responses deteriorated progressively and independently of the increase of compound action potential thresholds. A sudden (conductive) hearing loss and a poor response to suprathreshold stimulation might indicate inner ear damage secondary to a perilymphatic fistula. PMID- 2319889 TI - Longitudinal effects of single-channel cochlear implantation on voice quality. AB - No studies have reported longitudinal group data on the voice characteristics of adult participants with adventitious profound sensorineural hearing loss before and after single-channel cochlear implantation. This study investigated voice fundamental frequency, intensity, and speaking duration preimplantation and longitudinally 1-day, 6-months, and 1-year poststimulation. Results revealed only fundamental frequency 1-day poststimulation to be significantly different from preimplantation. Trends for all three variables, i.e., lowered Fo, reduced intensity, and shortened speaking duration (a faster rate), however, moved toward the measures that typify normal-hearing speakers. PMID- 2319890 TI - Postsurgical follow-up study of patients with severe polypoid degeneration. AB - This report summarizes our experiences with 23 women whose bilateral severe polypoid degeneration was managed surgically and who have been followed over a 2- to 7-year postoperative period. In our study group, polypoid degeneration did not reappear if the patient stopped smoking and practiced healthy vocal hygiene. About 25% of those who continued to smoke after surgery evidenced return of the disease, usually within 2 to 3 years. Reappearance of polypoid degeneration appeared most strongly related to the smoking variable alone or in combination with vocal abuse and/or medications that can cause edema. Neither vocal abuse nor medications appeared to be primary causal factors. The return of polypoid degeneration, in its earliest stages, was detected first via laryngeal examination. PMID- 2319891 TI - Quantitative bacteriology of closed-suction wound drainage in contaminated surgery. AB - This study was designed to evaluate the predictive value of quantitative bacteriology of closed-suction postoperative wound drainage in identifying the patient likely to develop wound infection as well as its subsequent flora. Forty one patients undergoing major cancer surgery of the head and neck were studied. Postoperatively, closed-suction wound drainage was cultured, and anaerobic and aerobic bacterial isolates were quantitated. The wound infection rate was 20% (8/41). No trend toward increased rate of wound infection with increased numbers of bacteria colonizing the wound was observed. Additionally, there was no consistent correlation between species of bacteria isolated from closed-suction wound drainage and recovery from subsequent wound infection. Quantitative bacteriology of closed-suction wound drainage after contaminated head and neck cancer surgery does not accurately predict which patients were likely to become infected, or the probable bacteriology of subsequent wound infection. PMID- 2319892 TI - Temporal bone findings in a case of bilateral Meniere's disease treated by parenteral streptomycin and endolymphatic shunt. AB - A patient with bilateral Meniere's disease who had progressive hearing loss and intractable vertigo was treated at ages 60 and 62 with parenteral streptomycin to ablate vestibular function, and at age 74 by a left endolymphatic shunt procedure. He was confined to a wheelchair because of ataxia from age 75 until the time of his death at age 81. Both temporal bones show congenitally hypoplastic endolymphatic sacs and severe endolymphatic hydrops consistent with Meniere's disease. There was atrophy of the striae vasculares and loss of cochlear neurons consistent with presbycusis. A loss of hair cells in the cristae and saccules was consistent with streptomycin ototoxicity. In the left ear the Silastic strip that was intended to function as an endolymphatic shunt into the mastoid lies encased in fibrous tissue and failed by 4.5 mm to reach the hypoplastic endolymphatic sac. PMID- 2319893 TI - A comparison of the cartilaginous rib graft and Evans-Todd laryngotracheoplasties for subglottic stenosis. AB - Cartilaginous rib graft interposition and Evans-Todd laryngotracheoplasties were compared in 21 patients with similar degrees of subglottic stenosis. The ultimate success of the repair was similar, but complications were more frequent with the Evans-Todd laryngotracheoplasty. Stent removal and decannulation were accomplished earlier with the cartilage graft laryngotracheoplasty--an average of 21 days to decannulation after stent removal versus 66 days for the Evans-Todd procedure. Granulation tissue was almost universal in the Evans-Todd procedure, and accounted for the long decannulation time. This retrospective study is used as a basis to discuss the relative merits of the two procedures. PMID- 2319894 TI - Computer-aided 3-D temporal bone anatomy for cochlear implant surgery. AB - To define anatomical relationships important in cochlear implantation, computer aided three-dimensional reconstruction and measurement of middle and inner ear structures in six normal temporal bones were performed. Our findings were as follows: 1. When viewed from the posterior hypotympanotomy (facial recess) approach, the inferior 10% to 30% of the round window (RW) membrane was visible in only half the cases. 2. The most inferior portion of the basal turn of the scala tympani was not only inferior but also slightly anteriorly behind the RW membrane in more than half the cases. 3. The shortest distances from the aperture of the RW niche and from the margin of the RW to the stapes head were 2.38 +/- 0.33 and 2.15 +/- 0.22 mm, respectively. 4. The distance between the RW and the most inferior portion of the basal turn scala tympani was 5.15 +/- 0.34 mm. 5. The direction of the electrode advancement lay at a sharp angle to the inferior part of the RW (mean 31.9 +/- 3.6 degrees). 6. The direction from the RW to the most inferior portion of the basal turn scala tympani lay 16.0 +/- 5.3 degrees anteroinferior to the direction of the advancement of the electrode to the RW. 7. The distance between the margin of the RW and the basilar membrane of the cochlea was 0.58 +/- 0.10 mm at the superior aspect of the RW, and was 1.23 +/- 0.12 mm at the lateral aspect of the RW. 8. Dissecting away less than 1 mm (mean 0.7 +/- 0.27 mm) of the RW margin inferiorly or inferolaterally was enough to permit straight insertion of the electrode in most cases. PMID- 2319895 TI - Permanent tracheostomy with cervical lipectomy. PMID- 2319896 TI - Transnasal pituitary tumor surgery. PMID- 2319897 TI - Video endoscopic sinus surgery: a two-handed technique. PMID- 2319898 TI - Effects of peritonsillar infiltration. PMID- 2319899 TI - The management of nerve damage in the leprosy control services. PMID- 2319900 TI - Leprosy in Portugal 1946-80: epidemiologic patterns observed during declining incidence rates. AB - Compulsory notification of leprosy in Portugal formed the basis for the establishment of a national patient registry used in an epidemiological study. Highest incidence rates were observed in the coastal counties in the middle of Portugal and particularly in the municipalities with a high annual rainfall. Peak incidence rates in males was observed at the age of 25-29 years against 50-59 in females. A continuous and increasing decline in incidence rates was observed throughout the observation period, 1946-80. Towards the end of the period the slopes of the incidence curves seemed to be identical with those observed in other countries where leprosy has previously been eradicated. This is consistent with the notion that towards the end of an endemic situation no new transmission of the disease occurs, and the incidence curve takes the shape of the right part of the distribution of incubation periods which apparently is uniform in leprosy, irrespective of time and place. The pattern observed in other areas during declining incidence rates, of an increase in age at onset by year of onset together with a lack of increase in age at onset by year of birth was confirmed by the Portuguese data, also consistent with a break in the transmission of the disease a long time before the final termination of the endemic situation. PMID- 2319901 TI - The role of intrahousehold contact in the transmission of leprosy. AB - This study examines the role of intrahousehold contact in the transmission of leprosy using the case control methodology. The study was done in the leprosy control area of the Community Health and Development (CHAD) Programme of the Christian Medical College. Three age, sex and village matched controls were selected for each case. This study shows that persons with intrahousehold contact with leprosy have a higher risk of acquiring leprosy compared with those who did not (RR 2.509; 95% confidence limits 1.23-5.109). PMID- 2319902 TI - A re-appraisal of clinical and bacteriological criteria in the implementation of multiple drug therapy for leprosy control programmes and proposals for their better use. AB - Behind the appraisal of criteria above and our proposals, is the question 'To what extent and for what purpose should slit-skin smears be used in programmes implementing MDT?' The answer may lie somewhere between the extreme of abolishing them altogether and the present situation, in which many people seem to think that a comprehensive service has to be provided at many levels, including the periphery, almost regardless of quality and with minimal supervision. Our plea is twofold: (1) the much wider use of standardized clinical, as opposed to bacteriological, criteria for the grouping of the patients, the termination of treatment in multibacillary cases and follow up, and (2) the abolition of the routine use of slit-skin smear examination in the field, coupled with the phasing out of unsupervised peripheral units of doubtful quality and the identification of one laboratory at central or provincial level which is able to provide a reliable, high quality service for smears in selected cases. Clearly these proposals will not solve all the operational and methodological problems. There is an urgent need for research on the best ways to implement MDT on a large scale. But the truth of the matter is that 7 years after the WHO recommendations and for reasons which have so far been poorly defined, less than half the world's registered cases have so far received MDT. Most of the registered cases continue to take a form of treatment, dapsone monotherapy, which was condemned over 10 years ago as being hazardous on account of the dangers of resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2319903 TI - Plastic footwear for leprosy. AB - The anaesthetic foot in leprosy poses the most major problem in the rehabilitation of its patients. Various attempts have been made to produce protective footwear such as the microcellular rubber-car-tyre sandals. Unfortunately these attempts have had little success on a large scale because of the inability to produce them in large numbers and the stigma attached to such unusual footwear. While such footwear may be superior to the 'tennis' shoe in protecting the foot from injury by the penetration of sharp objects, it fails to distribute the weight-bearing forces which is the major cause of plantar damage and ulceration in the anaesthetic foot. This can be achieved by providing rigidity to the sole, as demonstrated by the healing of ulcers in plaster of paris casts or the rigid wooden clog. A new type of moulded plastic footwear has been evolved in conjunction with the plastic footwear industry which provides footwear that can be mass produced at a low price and which overcomes the stigma of leprosy. Controlled rigidity is provided by the incorporation of a spring steel shank between the sponge insole and the hard wearing plastic sole. Trials have demonstrated both the acceptability of the footwear and its protective effects as well as its hard wearing properties. PMID- 2319905 TI - Comment on 'leprosy in children'. PMID- 2319904 TI - How to detect leprosy in some patients with only localized sensory loss. PMID- 2319906 TI - Gastrin and epidermal growth factor induction of ornithine decarboxylase in rat colonic explants. AB - An organ culture system was utilized to examine the effect of gastrin (G-17-I) and epidermal growth factor (EGF) on colonic mucosal ornithine decarboxylase (ODC) activity, and the expression of the ODC gene. Exposure of colonic mucosal explants to either gastrin or EGF (50-500 ng/ml) for only 4 h resulted in a profound stimulation (150-600%) in ODC activity over the basal level. These increases were essentially abolished by difluoromethylornithine (DFMO; 2 nmol/ml) or CaCl2 (2 umol/ml). Gastrin also activated the ODC gene in the colonic mucosa as evidenced by increased steady-state ODC mRNA levels in the colonic mucosal explants after 4 h exposure to the hormone, when compared with the controls. It is concluded that colonic mucosal ODC is responsive to both gastrin and EGF. PMID- 2319907 TI - Prostaglandin D2 modulates human neutrophil intracellular calcium flux and inhibits superoxide release via its ring carbonyl. AB - We compared the effects of prostaglandin D2 (PGD2), prostaglandin F2 alpha (PGF2) and various ketones on superoxide (OX) release by human neutrophils, which had been stimulated by N-formyl methionyl leucyl phenylalanine (FMLP). Our data suggested that the ring carbonyl of PGD2 is essential to its inhibitory effect on OX release, but the carbonyl group as a ketone, alone is not sufficient. Using the fluorescent Ca2+ probe, Fura-2AM, we found that PGD2 increased the rate of decline of FMLP stimulated intracellular free Ca2+ (Ca)i, but that PGF2 had no effect. cAMP altered FMLP stimulated (Ca)i, in a pattern similar to PGD2. Furthermore, the ring carbonyl of PGD2 is crucial to its effect on OX as well as on (Ca)i. PMID- 2319908 TI - Saccharin induces changes in adenylate cyclase activity in liver and muscle membranes in rats. AB - The non-nutritive sweetener, saccharin, was found to stimulate significantly the activity of adenylate cyclase in membranes derived from skeletal muscle of rat. Sodium saccharin enhanced adenylate cyclase activity in a dose-related manner, and this activation appeared to be dependent on the presence of guanine nucleotides, suggesting the involvement of GTP-binding proteins. In membranes derived from the liver, however, sodium saccharin had an effect which was dependent on the concentration of membranes used in the adenylate cyclase assay. In high concentrations of membranes, sodium saccharin had a stimulatory effect, while in low concentration an inhibition was observed. PMID- 2319909 TI - Halothane enhances the phosphorylation of H1 histone and rat brain cytoplasmic proteins by protein kinase C. AB - The effect of halothane, a typical volatile anesthetic, on the calcium- and phospholipid-dependent protein kinase (PKC), which is one of the key enzymes of membrane signal transduction, was examined. PKC was partially purified from the cerebral tissue of male Wistar rats. Halothane increased PKC-mediated phosphorylation of calf thymus H1 histone in the presence or absence of phorbol ester or diolein, and also increased phosphorylation of the rat brain cytosolic proteins (47 kDa and 80 kDa). A similar but slight increase in H1 histone phosphorylation was observed with isoflurane and enflurane, less lipid soluble volatile anesthetics. These findings suggest that halothane may increase PKC mediated phosphorylation by the modification of phospholipid membrane and affect membrane signal transduction of the nerve cell under the anesthetic state. PMID- 2319910 TI - NH2-terminal big gastrin immunoreactivity in human urine. AB - The concentrations and molecular forms of urinary and plasma gastrin from normal subjects were studied by radioimmunoassays using two region-specific antisera. Urinary concentration of NH2-terminal big gastrin (G-34) immunoreactivity was several hundred times as great as that of COOH-terminal gastrin immunoreactivity. Fractionation of urine extract showed a broad giant peak of NH2-terminal G-34 immunoreactivity (gastrin fragments "U") eluting in a later position than G-34(1 17) by Sephadex G-50 column chromatography. HPLC revealed that urinary NH2 terminal G-34 immunoreactivity was composed of four fragments including G-34(1 8), G-34(1-9), and G-34(1-10). Sephadex G-50 column chromatography of plasma extract revealed two or three peaks of NH2-terminal G-34 immunoreactivity, and a major peak eluted in the same position as urinary gastrin fragments "U". These results and data on renal clearances suggest that most of all gastrin fragments "U" in plasma are excreted in urine without renal reabsorption, whereas almost all of plasma COOH-terminal gastrin peptides including G-34 and little gastrin (G 17) are removed and metabolized in the kidney. PMID- 2319911 TI - Inhibition of alpha-aminoisobutyric acid uptake by mastoparan in Madin-Darby Canine Kidney cells. AB - Mastoparan, a wasp venom, was found to inhibit Na(+)-dependent net alpha aminoisobutyric acid (AIB) uptake in Madin Darby Canine Kidney (MDCK) cells. Mastoparan also produced a significant increase in AIB efflux when compared to controls. Pretreatment of MDCK cells with 2 mM neomycin attenuated mastoparan's inhibition of net AIB uptake and completely suppressed mastoparan-mediated increases in AIB efflux when compared to controls. These data suggest that mastoparan's inhibition of net AIB uptake involves more than a single basic mechanism. PMID- 2319912 TI - Standards and norms in small area analysis. AB - Description of the type and amount of variation in the use of health care services across geographic areas is a well-established method of inquiry encompassing the analysis of both medical and surgical treatment modalities. PMID- 2319913 TI - Peripheral vascular disease in diabetes mellitus. AB - In caring for diabetic patients, we must broaden our focus beyond just treatment of hyperglycemia and begin to view diseases of the vascular system as critical sites for preventive efforts. PMID- 2319915 TI - A comment on the doctor and hospital responsibility. PMID- 2319914 TI - Brain injured patients: comorbidities and ancillary medical requirements. AB - Traumatic brain injuries are medically and economically devastating conditions. Rehabilitation may be affected by premorbid factors such as substance abuse and violence. Successful rehabilitation is an ongoing process. PMID- 2319916 TI - [Cytomorphologic monitoring in the complex treatment of patients with cancer of the endometrium]. AB - The paper is devoted to analysis of clinicomorphological data on the status of a primary endometrial tumor in 209 endometrial cancer patients, treated by radical and palliative radiation therapy (112 patients) and the combined method (88 patients) including preoperative intensive concentrated intracavitary irradiation and hormonotherapy. Dynamic cytological monitoring was performed during radiation therapy and in a period up to 12 mos. after the discontinuation of antitumor therapy. Clinicoinstrumental investigations are of low informative value to make conclusions of the time course of tumor regression and its rates, and of the outcome of disease. Dynamic cytomorphological monitoring is an important stage in the integrated diagnosis of endometrial cancer, especially in patients who cannot be operated upon as a result of tumor spreading or somatic contraindications. PMID- 2319917 TI - [Radionuclide study of the absorption of nutrients]. AB - The authors present the theoretical rationale, algorithm and results of verification of a new radionuclide method for the determination of nutritive absorption. The proposed method allows the determination of the amount of a labeled unabsorbed food ingredient without the collection and radiometry of feces, with a high degree of significance. PMID- 2319918 TI - [The diagnostic value of the status of urinary taurine in the early stages following the irradiation of animals]. AB - A study of the features of taurine excretion early after irradiation of animals in comparison with the peripheral blood level of leukocytes is necessary for the development of methods of early diagnosis and prediction of an outcome of radiation disease. The paper is concerned with a study of the correlation between a dose of ionizing radiation and enhanced taurine excretion with urine in rats and dogs as compared to the time course of the blood level of leukocytes, an indicator used for the diagnosis of radiation disease. The doses were 2-10 Gy for rats and 5-15 Gy for dogs. Intensive taurine excretion was shown to be an early (recorded in the first hours after radiation exposure), stable and dose-dependent body reaction. The authors discussed the problem of the appropriateness of the use of this test for the diagnosis and prognosis of an outcome of acute radiation disease in combination with common indices. PMID- 2319919 TI - [Ability of the lymphocytes in the peripheral blood of oncologic patients to repair DNA]. AB - A study was made of the level of reparative capacity of peripheral blood lymphocytes of cancer patients in response to DNA damaging R-radiation testing at a dose of 250 Gy before the next course of cancer chemotherapy. A low capacity of peripheral blood lymphocytes for reparation of DNA or its complete suppression is characteristic for most cancer patients irrespective of a nosological entity and the number of cancer chemotherapy courses in their history. The frequency of cancer patients with the initially suppressed capacity of peripheral blood lymphocytes for DNA reparation has an increasing tendency depending on the spreading of a process. These data can serve as an additional criterion of prognosis of complication during antitumor therapy. PMID- 2319920 TI - [A radionuclide study of the lungs in sarcoidosis]. AB - Altogether 43 patients with a primary diagnosis of sarcoidosis of the respiratory organs were investigated to reveal the presence and spreading of dysfunction of external respiratory indices and indices of capillary blood supply in patients with sarcoidosis. Of them sarcoidosis was confirmed clinically in 36. Of the other 7 patients 5 had tuberculosis of various forms, one--lung cancer, and one- chronic obstructive bronchitis. All the patients were subjected to radionuclide investigation with 133Xe, 99mTc-microspheres, and 67Ga-citrate. The results obtained permit objective assessment of the presence and a degree of disorders of external respiration and capillary blood supply and the determination of disease activity on the basis of 67Ga-citrate accumulation that is important for the evaluation of therapeutic efficacy. The results were assessed with relation to a degree of sarcoidosis and the type of a pathological process. PMID- 2319921 TI - [Hyperglycemia as a means of increasing the efficacy of hyperthermia in radiotherapy of tumors]. AB - In experiments on mice with Ehrlich carcinoma transplanted into the thigh the authors determined a gain in tumor heating from the use of induced hyperglycemia (IH) during thermoradiotherapy. Tumors were irradiated at a dose of 20 Gy followed in 3 h by local hyperthermia (HT) by emerging a tumor into water at 40 45 degrees C for 30 min. IH followed irradiation (i.e. 3 h before HT) in the form of 5-time ip administration of glucose at a total dose of 10.4 g/kg for 2 h. Isoeffective tumor damage was achieved in irradiation combined with HT (45 degrees C) only and in irradiation with subsequent IH and HT (40 degrees C), i.e. a gain in the temperature of heated water as a result of glucose use was 5 degrees C. In the independent use (without irradiation) of HT this value was equal approximately 2.5 degrees C. Thermometric investigations have shown that these effects are partially accounted for by better heating (by 0.2-0.4 degrees C) of tumor tissue in IH. However glucose action was mainly connected with resultant physiological changes in tumors like a noticeable decrease in pH and stable disorder of the blood flow. PMID- 2319922 TI - [The clinical application of new methods of magnetic resonance tomography]. AB - MR-tomography was used for investigation of 129 patients with various diseases of the kidneys, liver, pancreas, organs of the small pelvis, brain and spinal marrow. Possibilities of the use and practical value of new MRT methods--MR urography and MR-myelography (MRu and MRm) were studied. They made it possible to detect within a short period of time (40-60 sec.) the presence of fluid in an examined volume. MRu was the most informative method in cystic lesions of various organs looking like round-shaped formations with a high intensity signal. MRm was highly informative in the diagnosis of syringomyelia, informative for the determination of the state of the brain ventricular system. MRm performed in different planes and their summation with images of common MR-sections makes the interpretation of the obtained data much easier. MRm is desirable in suspected fluid in an examined volume or in order to specify the state of the cerebral liquor system. PMID- 2319923 TI - [Cholescintigraphy in the evaluation of duodenogastric reflux in cholelithiasis]. AB - A total of 103 patients with cholelithiasis and those operated on one year ago were investigated using modified cholescintigraphy permitting the determination of a size, duration and spreading of the gastroduodenal reflux. Dynamic cholescintigraphy was shown to be an effective method of the diagnosis and quantitative estimation of the gastroduodenal reflux in patients with cholelithiasis and patients after cholecystectomy. In patients with the postcholecystectomy syndrome the gastroduodenal reflux was detected more frequently, and its quantitative indicators were lower than those in patients with cholelithiasis. PMID- 2319924 TI - [Volumetric standard sources for the metrological certification of spectrometers for measuring human internal irradiation]. AB - The system of metrological measurements using spectrometers of human radiation (SHR) envisages the development, investigation and attestation of sources of volumetric activity simulating an object of investigation. The authors devised a unified solid-body phantom, representing a set of standard volumetric sources in the form of rectangular modules and a method of their distribution. When assembled, the phantom imitates the human body containing a radionuclide, regularly distributed by the volume. Different variants of the packing of the constituent elements makes in possible to simulate the human body in a wide range of age groups and height and weight correlations. Experimental investigations on the standardization of various types of SHR on the basis of this phantom have shown good convergence of the results of measurements within the limits of 15% error. PMID- 2319925 TI - [Thermoradiotherapy of cancer of the endometrium]. AB - The paper is concerned with the consideration of technical potentialities of local UHF-hyperthermia with regard to combined radiotherapy of endometrial cancer. The authors performed comparative analysis of thermoradiotherapy of a tumor and adjacent normal tissues and of combined radiotherapy as an independent method. The results of this investigation have shown that a decrease in a single focal dose per fraction, taking into account the DMF of hyperthermia in thermoradiotherapy, the same therapeutic effect on a tumor being preserved like in radiotherapy, reduces the frequency of radiation reactions of adjacent normal organs and tissues. PMID- 2319927 TI - 37th annual meeting of the American College of Sports Medicine. May 22-25, 1990, Salt Lake City. Abstracts. PMID- 2319926 TI - Moral dimensions of public policy formation: guidelines for nurses. PMID- 2319928 TI - Investigations concerning the potential for using 1H NMR relaxometry or high resolution spectroscopy of plasma as a screening test for malignant lung disease. AB - In 158 plasma samples, obtained from patients with lung carcinoma, lung metastases, and infectious or inflammatory lung diseases and from healthy controls, the NMR relaxation times T1 and T2 of water protons were measured at a resonance frequency of 20 MHz by pulsed NMR techniques and adjusted to a standardized total plasma protein concentration. For one-third of these samples water-suppressed 500-MHz 1H NMR spectroscopy at 37 degrees C was used (a) to determine the widths of the composite lipid methyl and methylene signals, and (b) to quantitate individual lipid methylene signal components that could be detected in resolution-enhanced spectra. In addition, hematological parameters and the plasma levels of several acute phase proteins and apolipoprotein-A were monitored. No diagnostically significant differences between lung carcinoma patients and patients with nonmalignant lung disease could be found for any of the plasma NMR parameters, nor could T1 or lipid linewidth data distinguish between any patient group and healthy controls. However, the mean T2 was significantly shortened by about 15% for any kind of lung disease compared to healthy controls. Similar but less significant results were found for apolipoprotein-A levels. A linear discriminant function, calculated from the apolipoprotein-A and T2 data, did not improve the differentiation between malignant and nonmalignant lung disease but did improve the discrimination between tumor patients and healthy controls up to a sensitivity and specificity of 80 and 96.5%, respectively. T2 correlates inversely with plasma fibrinogen levels and the blood sedimentation rate and, therefore, appears to monitor a general inflammatory status of a tumor patient rather than the presence or absence of cancer. For all groups except healthy pregnant women, the lipid methylene composite signal linewidth correlates inversely with the fraction of mobile triglyceride present (mainly as VLDL), as estimated from resolution enhanced spectra. PMID- 2319929 TI - Magnetic relaxation in blood and blood clots. AB - Nuclear magnetic relaxation rates are measured for whole blood, blood plasma, whole blood clots, and plasma clots in vitro. Relaxation rates are linear in the hematocrit and transverse relaxation rates are significantly greater than longitudinal relaxation rates. Longitudinal relaxation rates measured from 0.01 to 42 MHz for proton Larmor frequencies are found to decline monotonically with increasing magnetic field strength; however, the dispersion curves do not follow a simple Lorentzian behavior, which is anticipated in a suspension of particles in a solution of proteins having a distribution of molecular weights. The transverse relaxation rate is a function of the acquisition parameters, in particular, the choice of TE in either Hahn echo experiments or in echo-train experiments. The origin of this dependence of T2 on TE or the interpulse spacing in an echo train is identified with the exchange of water from inside the red blood cell to the outside and is only an important relaxation mechanism in the case where the blood cell membrane is intact and the cell contains deoxygenated hemoglobin. The dependence of the apparent transverse relaxation rate on the interpulse spacing in a Meiboom-Gill-Carr-Purcell pulse sequence provides the estimate that the mean residence time of water inside the blood cell is about 10 ms. These data provide a sound basis for understanding the dependence of magnetic images on magnetic field strength and the choices of the image acquisition parameters, TE and TR. PMID- 2319930 TI - Spectral baseline correction using CLEAN. AB - Baseline distortion in NMR spectroscopy, caused by the "dead time" between signal excitation and detection, makes quantitative interpretation difficult and is aesthetically displeasing. Here the use of the CLEAN algorithm for deconvolving the effect of signal dead time to produce a distortionless baseline is discussed. Unlike other nonlinear spectral estimation techniques, CLEAN is easy to program, easy to use, quite robust, and fast. PMID- 2319931 TI - 0.3-second FLASH MRI of the human heart. AB - Flow-suppressed FLASH MR images of the human heart have been recorded within a measuring time of 0.3 s using a 2.0-T whole-body research system (Siemens Magnetom) equipped with a conventional 10 mT m-1 gradient system. Subsecond imaging times have been achieved by reducing the repetition time to TR = 4.8 ms and by lowering the spatial resolution to 64 X 128 measured data points. The flip angle of the slice-selective radiofrequency (rf) pulses was adjusted to 10 degrees. Cardiac chambers, ventricular walls, and valves are well delineated in images from a single cardiac cycle using a field of 250 mm and a slice thickness of 8 mm. No motion artifacts were observed as a consequence of the short echo time of TE = 2.8 ms. Distinction between flowing blood and solid structures has been achieved by spatial presaturation of adjacent slices using two slice selective 90 degrees rf pulses preceding the entire imaging sequence. PMID- 2319932 TI - Echo-planar imaging with asymmetric gradient modulation and inner-volume excitation. AB - Single-shot echo-planar imaging is notoriously vulnerable to image artifacts, arising from the necessity of alternate echo time reversal during image reconstruction and from static field inhomogeneity. A technique for overcoming these problems, which further permits imaging on systems with relatively poor gradient waveforms, when data are collected always with the same gradient polarity, is presented. Subsectional and 3D volume imaging are presented as well as a novel phase-correction method for Hermitian symmetry in "half-Fourier" echo planar imaging. PMID- 2319933 TI - Extraction of cardiac and respiratory motion cycles by use of projection data and its applications to NMR imaging. AB - A technique of extracting cardiac and respiratory motion cycles by use of projection data is proposed and studied. These extracted cardiac and respiratory motion cycles are applied to the cine imaging of heart and motion artifact reduction in abdominal imaging instead of the conventional ECG gating devices. The basic concepts and their applications are discussed. Experimental results on human volunteers obtained with the KAIS 2.0-T whole-body NMR imaging system together with the pulse sequences used for the experiments are presented. PMID- 2319934 TI - Proton relaxation enhancement of albumin, immunoglobulin G, and fibrinogen labeled with Gd-DTPA. AB - Bovine serum albumin, immunoglobulin G, and fibrinogen were labeled with Gd-DTPA using a bifunctional chelating agent DTPA anhydride. The protein-(Gd-DTPA) conjugates had 1.4- to 2.0-fold greater longitudinal relaxivities at 0.02 and 0.44 T than the relaxivity of plain Gd-DTPA. The increase of longitudinal relaxivity was not directly related to the size of carrier protein. Up to 50 Gd DTPA chelates per protein, longitudinal relaxivity of the conjugates was proportional to the concentration of Gd and independent of the Gd/protein ratio. PMID- 2319935 TI - Cerebral metabolite dynamics during temporary complete ischemia in rats monitored by time-shared 1H and 31P NMR spectroscopy. AB - The changes in cerebral phosphorus metabolites, intracellular pH, and lactate during 30 min of complete global ischemia and 2 h of reperfusion were monitored by time-shared 1H and 31P in vivo NMR spectroscopy in rats. After the induction of ischemia, intracellular pH decreased from 7.14 +/- 0.01 to 6.32 +/- 0.10, and lactate concentration increased from 1.6 +/- 0.4 to 15.8 +/- 2.5 mumol/g; ATP and phosphocreatine were totally depleted, while inorganic phosphate increased 715 +/ 47%. Within 1 h after blood flow was restored, high-energy phosphates and lactate levels had recovered close to baseline levels. The changes in intracellular pH and lactate levels during ischemia and reperfusion correlated well. PMID- 2319936 TI - Detection of metabolic heterogeneity of human intracranial tumors in vivo by 1H NMR spectroscopic imaging. AB - Patients with intracranial tumors (gliomas) were examined by means of localized water-suppressed 1H NMR single volume spectroscopy and spectroscopic imaging. The 1H NMR spectra of the tumors exhibit signal intensities of the N-acetyl aspartate, choline compounds, and creatine plus phosphocreatine resonance lines that are different from the corresponding intensities observed on normal brain tissue. Also, for 6 out of the 10 patients examined so far, lactate resonance lines were detected in the tumor spectra. For one patient, abnormal 1H NMR spectra were obtained of a hemisphere which appeared normal with 1H NMR imaging. Metabolic heterogeneity of the tumorous regions could be demonstrated with 1H NMR spectroscopic imaging, using a spatial resolution in the order of 1 cm. These results suggest a spectrum of metabolic observations that may ultimately provide an important means for characterizing brain tumors. PMID- 2319937 TI - Snapshot FLASH MRI. Applications to T1, T2, and chemical-shift imaging. AB - Snapshot FLASH magnetic resonance imaging techniques have been developed to enable real-time imaging of MR parameters. The first realization of the method is based on a 64 X 128 FLASH tomogram acquired within 200 ms, using improved MR system hardware conditions. The soft tissue contrast obtained in FLASH MRI almost disappears by using flip angles of less than 5 degrees and repetition times of 3 ms. This work describes extensions of FLASH MRI placing conventional MR experiments before the whole imaging sequence. This creates images of any desired contrast without changing the measuring time. Examples of inversion-recovery T1, spin-echo T2, chemical-shift-selective, and spectroscopic FLASH MRI are presented. Further extensions to real-time MRI of blood vessels, diffusion coefficients, combination with two-dimensional MR spectroscopy experiments, and other nuclei are discussed. PMID- 2319938 TI - In vivo 13C nuclear magnetic resonance investigations of choline metabolism in rabbit brain. AB - The metabolism of choline in rabbit brain was studied by the noninvasive approach of in vivo 13C NMR spectroscopy. 13C-Enriched precursors were introduced into the brain. Surgery of the head skin was avoided through controlled localization of the surface coil. For long-term accumulation studies in brain, repeated subcutaneous injections proved to be advantageous over other forms of application. The resorption kinetics was calculated to be zero order which suggests slow delivery from the subcutaneous depots. Choline metabolism was studied by two approaches: [N-13CH3]choline and S-[13CH3]methionine were administered separately to adult and myelinating rabbits (Days 5 to 32), respectively, over 4 weeks. [N-13CH3]Choline and the 13CH3 group of methionine were incorporated into lecithin and sphingomyelin of brain myelin. In vivo kinetic studies of the turnover of these labeled structures were carried out. Choline and methionine are readily transported through the blood-brain barrier and utilized by the myelinating brain for the biosynthesis of its phospholipids. PMID- 2319939 TI - Coronary artery fistula: an abnormality affecting all age groups. AB - A coronary artery fistula is an abnormal communication between a coronary artery and a cardiac chamber, great vessel, or other vascular structure. It is an infrequent but potentially important abnormality that can affect any age group. Most are congenital in origin, although other etiologies, in particular trauma, have been identified. Many are small and found incidentally during coronary arteriography, while others are identified as the cause of a continuous murmur, myocardial ischemia, congestive heart failure, or, rarely, bacterial endocarditis. The diagnosis should be considered in any patient presenting with a continuous murmur or in the setting of congestive heart failure, myocardial ischemia, or bacterial endocarditis without an obvious etiology. The pathophysiologic mechanisms resulting in symptoms include cardiac volume overload due to the shunting of blood and reduction of the myocardial blood supply due to "coronary steal." The diagnosis of coronary artery fistula may be suggested by the finding of a continuous murmur in a precordial location, which is atypical for patent ductus arteriosus. Two-dimensional echocardiography may demonstrate dilated coronary arteries, and pulse-wave and color-flow Doppler examinations can display turbulent flow in the suspected fistula and its receiving chamber or vessel. Angiography is generally needed to confirm the diagnosis and elucidate anatomic detail. The natural history of coronary artery fistula is variable, with long periods of stability in some patients and gradual progression of symptoms in others. Small fistulas detected incidentally at the time of angiography do not require immediate surgical correction, but careful follow-up is indicated because the potential for enlargement with physiologically important shunting exists and cannot readily be predicted. Spontaneous closure is uncommon. Surgical repair of the fistula is recommended for symptomatic patients and for some without symptoms because a quantitatively small shunt does not predict freedom from future symptoms or complications. Those selected for medical management must be followed closely. PMID- 2319940 TI - Rheumatoid pericarditis: clinical features and survival. AB - We describe the clinical characteristics and actuarial survival of a consecutive cohort of 41 patients with rheumatoid arthritis and clinical pericarditis who were seen at the Mayo Clinic between 1970 and 1987 and followed up until death or through 1987. The survivors were followed up for a median of 5.1 years. Approximately three-fourths of our patients had acute pericarditis, the remainder having recurrent acute pericarditis, chronic pericarditis with effusion, or chronic constrictive pericarditis. Most patients had symmetrical joint swelling, morning stiffness, subcutaneous nodules, rheumatoid factor, and classic radiographic changes of rheumatoid arthritis. Common extra-articular features included fatigue, loss of weight, and fever. Dyspnea or orthopnea, typical pericardial pain, peripheral edema, tachycardia, tachypnea, a diminished mean blood pressure, a pericardial friction rub, jugular venous distension, rales, radiographic evidence of cardiomegaly and pleural effusions, and abnormal echocardiograms were the most common cardiac manifestations. An elevated erythrocyte sedimentation rate and anemia were other common laboratory findings. Our cohort demonstrated decreased survival in comparison with an age- and sex matched North Central white population (from the upper midwestern United States), especially during the first year after diagnosis. Increasing age, the presence of other heart disease, an increasing total number of other extra-articular manifestations of rheumatoid arthritis, jugular venous distention, and a lower mean blood pressure were associated with decreased survival. PMID- 2319941 TI - Chlorpromazine-induced immunopathy: progressive increase in serum IgM. AB - Long-term chlorpromazine therapy has been associated with the asymptomatic development of a high incidence of antinuclear antibodies, coagulation inhibitors, and increased serum levels of IgM. The purpose of this study has been to characterize the natural history of this chlorpromazine-induced (CPZ) immunopathy. To this end we carried out a prospective study of schizophrenic patients with the immunopathy to compare the effect of continuing CPZ versus switching to haloperidol therapy. Although no marked differences were noted between the 2 groups at the end of 5 years, 6 of 29 patients who continued to receive CPZ, as compared to none of 14 patients on haloperidol, had progressive elevations of serum IgM. In spite of a high incidence of antinuclear antibodies, none of the patients developed a lupus-like syndrome. One patient, however, who had been maintained on CPZ for more than 15 years, developed Waldenstrom macroglobulinemia, as characterized by an IgM monoclonal gammopathy and a lymphocyte immunoglobulin heavy and kappa light chain gene rearrangement. Another CPZ-treated patient developed immune thrombocytopenia. Based on the potential serious sequelae of prolonged stimulation of the immune system by CPZ, we recommend that patients who develop an increase in serum IgM while on CPZ be switched to other types of anti-psychotic medications. PMID- 2319942 TI - Molecular evolution of the zinc-containing long-chain alcohol dehydrogenase genes. AB - Phylogenetic relationships and rates of nucleotide substitution were studied for alcohol dehydrogenase (ADH) genes by using DNA sequences from mammals and plants. Mammalian ADH sequences include the three class I genes and a class II gene from humans and one gene each from baboon, rat, and mouse. Plant sequences include two ADH genes each from maize and rice, three genes from barley, and one gene each from wheat and two dicots, Arabidopsis and pea. Phylogenetic trees show that relationships among ADH genes are generally consistent with taxonomic relationships: mammalian and plant ADH genes are classified into two distinct groups; primate class I genes are clustered; and two dicot sequences are clustered separately from monocot sequences. Accelerated evolution has been detected among the duplicated ADH genes in plants, in which synonymous substitutions occurred more often within the coenzyme-binding domain than within the catalytic domains. PMID- 2319943 TI - Phylogenetic analysis of nucleoproteins suggests that human influenza A viruses emerged from a 19th-century avian ancestor. PMID- 2319945 TI - [Cryptosporidiosis in children from 1 to 2 years of age, with acute diarrhea in Belem, Para, Brazil]. AB - Two hundred and one samples obtained from 61 children were examined for Cryptosporidium infection during a period of 12 months. One hundred fifteen specimens were collected during diarrhoea episodes and the remaining 86 obtained out of diarrhoea period, as controls. All samples were examined by a modified Ziehl-Neelsen staining method. Cryptosporidium was detected in 6 (5.2%) of 115 samples from diarrhoeic children. All non-diarrhoeic control patients were negative for Cryptosporidium. The present study suggests that Cryptosporidium is an agent of self-limited diarrhoea among immunocompetent children from Belem, Para. PMID- 2319944 TI - Duplication and variation of the thermostable direct haemolysin (tdh) gene in Vibrio parahaemolyticus. AB - The relationship between phenotypic variation and nucleotide sequence variation of the gene encoding Vibrio parahaemolyticus thermostable direct haemolysin (tdh gene) was examined. Strains showing a typical haemolysin-positive phenotype carried two chromosomal gene copies (designated tdh1 and tdh2) while tdh-gene positive strains showing a weakly positive or negative haemolysin phenotype possessed only a single chromosomal gene copy. Both gene copies from a typical haemolysin-positive strain were cloned and sequenced and possessed 97.2% homology. Comparison of the amino acid sequence predicted from the nucleotide sequence with the protein sequence determined by Edman degradation as well as construction of a tdh1-deficient yet haemolytic strain of V. parahaemolyticus suggest that the tdh2 locus is primarily responsible for the haemolytic phenotype. Two other tdh gene copies were cloned from a phenotypically negative strain which was unusual in that it contained one gene copy on a plasmid (designated tdh4) in addition to a single copy on the chromosome (tdh3). Both tdh3 and tdh4 were expressed in Escherichia coli and TDHs with haemolytic activity were produced. These gene copies were sequenced and shared 96.7% homology with the tdh1 gene. The V. parahaemolyticus strain carrying tdh3 and tdh4 gene copies did not produce detectable amount of tdh-specific RNA transcript. It seems, therefore, that differences in the transcriptional control are primarily responsible for the differences seen in haemolytic phenotype. PMID- 2319946 TI - Characterization of plasma membrane polypeptides of Trypanosoma from bats. AB - Cell surface proteins of Trypanosoma dionisii, Trypanosoma vespertilionis and Trypanosoma sp. (M238) were radiodinated and their distribution both in the detergent-poor (DPP) and detergent-enriched phase (DRP) was studied using a phase separation technique in Triton X-114, as well as polyacrylamide gel electrophoresis in sodium dodecyl sulphate (SDS-PAGE). Significant differences were observed in the proteins present in the DRP when the three species of trypanosoma were compared. Two major bands with 88 and 70 KDa were observed in T. sp. (M238) but were not detectable in T. dionisii and T. vespertilionis. Three polypeptides with 96, 77 and 60 KDa were identified in the DRP of T. vespertilionis. Three major bands with 84, 72 and 60 KDa were observed in the DRP of T. dionisii. Two polypeptides with 34-36 KDa present in the DPP, were observed in the three Trypanosome species analyzed. Our observations show that T. sp. (M238) has characteristic surface polypeptides not found in T. dionisii and T. vespertilionis. PMID- 2319947 TI - Cutaneous phaeohyphomycosis caused by Scytalidium lignicola - report of the first three cases in Brazil. PMID- 2319948 TI - Zoonotic cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis associated with domestic animals in Venezuela and Brazil. AB - After outbreaks of cutaneous leishmaniasis in Solano State, Venezuela, 5% of the population had parasitized ulcers while after similar outbreaks in Mesquita, Rio de Janeiro State, Brazil, 9% had the disease. In these foci children, including some under six years of age, were affected. There was no significant difference in the occurrence of the disease according to sex or type of employment. In Solano, 3% of dogs and 28% of donkeys had parasitized lesions, while in Mesquita these indices were 19.8% and 30.8% respectively. The parasite from man, dogs and equines was identified as Leishmania (Viannia) braziliensis, by zymodeme and serodeme characterization. In these foci there is evidence suggesting that leishmaniasis is a zoonosis, possibly with equines and dogs as reservoirs, although both a wild enzootic cycle and the role of man as a source of infection can not be ruled out. Transmission is assumed to occur peridomestically by sandfly vectors such as Lutzomyia panamensis in Venezuela and Lutzomyia intermedia in Brazil. Information about the origin of these foci suggests that infected equines may be an important factor in the dissemination of the parasite in a peridomestic situation where these sandflies are abundant. PMID- 2319949 TI - [Xenodiagnosis using Lutzomyia youngi in Venezuelan cases of cutaneous leishmaniasis due to Leishmania braziliensis]. AB - Eight patients infected with Leishmania braziliensis were used for xenodiagnosis with Lutzomyia youngi, before and after specific antileishmanial treatment with "glucantime" and "gabbromycin". All of them infected sandflies fed on the borders of the skin lesions before the treatment, suggesting that infected persons might act as reservoirs of infection for an indoor-biting sandfly species. The negative results obtained by xenodiagnosis carried out after specific treatment of the same individuals indicated cure of the patients, and a reduction of risk for further intradomiciliary transmission. PMID- 2319950 TI - [Molluscacide activity of piquerol A isolated from Piqueria trinervia (Compositae) on 8 species of pulmonate snails]. AB - In laboratory trials an aqueous solution of Piquerol A from Piqueria trinervia, collected in several regions of Mexico, showed a molluscicide action on the adults of eight different pulmonates snails species: Fossaria (Fossaria) humilis, F. (Bakerilymnaea) sp., Pseudosuccinea columella and Stagnicola attenuata from Mexico; F. (B.) cubensis and Physa cubensis from Cuba; P. columella and Biomphalaria glabrata from Brazil; B. glabrata from Puerto Rico; and S. elodes from U.S.A. The solution was tested at 50, 25 and 5 ppm concentration, for two periods of 6 and 24 hours, at room temperature (20-22 degrees C). A 100% mortality was obtained for all species at 50 ppm concentration after 6 hours of exposure; the same percentage at 25 ppm after 24 hours; and 60 to 100% mortality at 5 ppm concentration during 24 hours of exposure. No recovery was observed among any of the treated snails. Piquerol A is a sesquiterpene with low stability in nature and has previously only been tested as an insecticide and as an inhibitor of metabolism in cell cultures: no field trails have been made on its toxicity to other aquatic fauna as yet, but it is believed Piquerol A could be an excellent molluscicide for use in areas where focal transmission of schistosomiasis and fascioliasis are taking place. This is the first time experiments on molluscicides have been carried out in Mexico. PMID- 2319951 TI - [Interrelatio of acari Ixodidae and hosts of Edentata of the Serra da Canastra, Minas Gerais, Brazil]. AB - We received for examination a small colection of ticks captured in the National Park of the Serra da Canastra (MG), between 1979 and 1980. The authors demonstrated the existence of a broad co-accomodation of Amblyomma pseudoconcolor on Edentata of the family Dasypodidae, being Dasypodini the tribe more adjusted to this infestation. In conformity to the Figs 1 and 2, Dasypodini are probably the real hosts of A. pseudoconcolor and also the oldest hosts. For the first time, A. pseudoconcolor is also recorded on Cabassous tatouay, C. unicinctus, Priodontes maximus and Euphractus sexcincuts. Also for the first time A. pseudoconcolor and Amblyomma calcaratum were recorded in the State of Minas Gerais. The ectoparasites are deposited in the "Departamento de Parasitologia da Universidade Federal de Minas Gerais, Brasil". PMID- 2319952 TI - Phyllocaulis variegatus--an intermediate host of Angiostrongylus costaricensis in south Brazil. AB - Molluscs collected in five localities in the State of Rio Grande do Sul (Brazil) were digested and examined. The infected slugs were identified as Phyllocaulis variegatus and the larvae found were inoculated per os into mice. After 50 days, worms with the caracteristics of Angiostrongylus costaricensis were recovered from the mesenteric arterial system. The results establish the role of P. variegatus as intermediate host of A. costaricensis in south Brazil, where many cases of abdominal angiostrongyliasis have been diagnosed. PMID- 2319953 TI - [Natural parasitism of Bradybaena similaris (Ferussac, 1821) by Postharmostum gallinum Witenberg, 1923]. AB - A total of 4,298 snails Bradybaena similaris were collected from the rural area of Rio de Janeiro County and from the Counties of Paracambi and Itaguai, State of Rio de Janeiro. Two thousand and five of these snails had metacercariae in their pericardial cavity. The collecting was done between October 1983 and September 1986. The annual average prevalences were: 42.89% (1st year), 43.42% (2nd year) and 55.86% (3rd year). Experimental infection in chicks allowed the identification of these metacercariae as Postharmostomum gallinum. The small variation in size observed among metacercariae from the same host indicates that recruitment does not occur on a continuous basis. Statistical analysis showed no correlation between the snail size and the number of metacercariae in the pericardical cavity, and that the snail mortality observed in the laboratory was due to the parasitic infection. PMID- 2319954 TI - Patterns of serologic response to human immunodeficiency virus type 1 (HIV-1) in Brazilians with different clinical forms of HIV infection. AB - In order to investigate the IgG HIV-1 antibodies reactivity to structural components of the virus, 85 sera from infected Brazilians, comprising the total spectrum of HIV infection, were analysed by Western blot assay. The sera were confirmed as being positive to HIV with enzyme linked immuno assay (ELISA) and indirect immunofluorescence (IIF). Although the sera from patients reacted less intensively to the gag polypeptide of 55 KDa, no distinctive antigen reaction patterns were observed between sera patients with different clinical forms. Because of the higher frequency of reactivity to the gag p24 in AIDS patients, the patterns of anti-HIV IgG responses are similar to those observed in their African counterparts. PMID- 2319955 TI - Switching between memory and perception: moving attention or memory retrieval? AB - Weber, Burt, and Noll (1986) estimated that the time needed to switch attention between memory and perception was around 300 msec. The first two experiments in the present paper estimated switching time using a variation of their task. Subjects reported aloud lists of six items. The items were read off a computer screen (perception), recited from memory, or reported alternately from the two sources. The data show that the switching-time estimate is influenced by input/output compatibility, response-initiation times, and memory load. When these factors were controlled, estimated switching time dropped to around 100-150 msec. The data suggest, however, that the switch from perception to memory might be slower than the switch from memory to perception, which would invalidate the formula used to compute switching time. Experiment 3 tested the time for a single switch from perception to memory and a single switch from memory to perception by restricting report to one pair of items in the list. When the to-be-reported pair was precued, estimated switching time dropped to zero. When the pair was not precued, the memory-to-perception switching time remained at zero, but the perception-to-memory time was more than 400 msec. The pattern of results forced a reconceptualization of the task in terms of memory retrieval rather than attention switching. The attention-switching times appear to reflect processes required to select items from memory. PMID- 2319956 TI - Phonemic similarity effects and prelexical phonology. AB - Ten experiments were conducted on visually presented Serbo-Croatian words and pseudowords, comprising phonemically similar and dissimilar context-target sequences. There were five main results. First, phonemic similarity effects in both lexical decision and naming are independent of graphemic similarity. Second, phonemic similarity need not facilitate lexical decision; the direction of its effect depends on lexicality, target frequency, and type of similarity (specifically, the position of the phoneme that distinguishes context and target). Third, phonemic similarity expedites the naming of words and pseudowords, and to the same degree. Fourth, phonemic similarity is negated in naming, but not in lexical decision, when the visually presented context and target are stressed differently. Fifth, the phonemic similarity effect occurs even when the context is a masked pseudoword. These results are discussed in terms of a model in which word-processing units are activated routinely by phoneme-processing units, and in which compositionally similar word units, when activated, inhibit one another in proportion to each's familiarity. In this model, the phonemic similarity effect in naming is based on the states of phoneme units, whereas the phonemic similarity effect in lexical decision is based on the states of word units. Overall, the results comport with an account in which phonology is computed prelexically and automatically. PMID- 2319957 TI - Effects of word- and sentence-level contexts upon word recognition. AB - In the present experiments, we investigated the facilitatory effects of auditorily presented prime words in neutral sentence contexts upon visually presented target words. It is shown that when the target task is a lexical decision, facilitation is obtained when the relationship between the prime and the target is one of synonymy (and low association strength). When instead the target is an antonym (again of low association strength), there is no priming effect; lexical decision is facilitated only when the prime word is presented in isolation. In further experiments, it is shown that primes in sentence contexts can produce facilitation of antonyms if they are strongly associated, or in the absence of association if the target must be named. The results are explained in terms of an integration process, which checks for the coherence between an upcoming word and the highest available level of representation of the context, but which affects only responses in the lexical decision task. PMID- 2319958 TI - The effects of recoding and presentation format on recency and suffix effects. AB - The primary linguistic theory of Shand and Klima (1981) hypothesizes that stimuli that cannot be directly processed without recoding are not in the primary linguistic mode of the subject and thus should lead to lesser recency and associated suffix effects. In three experiments, different normal hearing subjects learned to pair American Sign Language (ASL) stimuli, visual "quasivocables" (QVs), word-like letter strings, and auditory QVs with common English words. In the first experiment, the subjects were given sequences of ASL or QV stimuli and required to recall the associated words in strict serial order. In two other experiments involving auditory and visual presentation, respectively, subjects who had never been given paired associate training were required to recall the English words that had previously been associated with the ASL and QV stimuli, in a standard suffix paradigm. The results showed recency and suffix effects to be present only with auditorily presented QVs and words. Contrary to the predictions of the primary linguistic hypothesis, greater recency and larger suffix effects were present with the auditory QVs than with the auditory words, although the QVs were not primary linguistic and the task involved forced recoding. Previous results showing recency with ASL stimuli in normal subjects were not replicated. It is concluded that recency and suffix effects are not related either to the primary linguistic mode of the subject or to stimulus recoding, as we and Shand and Klima have defined them. PMID- 2319959 TI - Misremembering a common object: when left is not right. AB - Three experiments were carried out to investigate people's memory for British coins. Two principal issues were studied. First, it has previously been shown that memory for U.S. pennies and other coins is surprisingly imperfect. How do other countries compare? It turned out that recall of the design of British pennies was, if anything, worse even than that of U.S. pennies. The situation was no better for a larger coin with an unusual shape. It is suggested that individual features are poorly remembered if they have low levels of meaningfulness, redundancy, identifiability, and discriminativeness. Second, in addition to this generally weak level of remembering, an instance of systematic misremembering was consistently observed. The Queen's portrait always faces to the right on British coins. Yet in all three experiments, the proportion of participants who recalled that the portrait faces to the right was so low (overall, 19%) that it was significantly less than even the 50% baseline to be expected from people in a state of complete ignorance. It follows that the participants were not in a state of complete ignorance. Rather, they relied upon extraneous knowledge of either a general or a specific nature (bias and schema hypotheses, respectively), whose importation into this domain was in fact invalid. The resulting belief that coin portraits face left was not right. PMID- 2319960 TI - An examination of the continuous distractor task and the "long-term recency effect". AB - The continuous distractor task has yielded a so-called "long-term recency effect" that appears to call into question the dual-storage explanation of serial position effects in free recall. In this study, we show that the "long-term recency effect" is really a short-term storage effect, resulting from adaptation to the repeated presentation of a particular type of distractor throughout the list. This adaptation, a time-sharing process, permits short-term storage to carry out its normal functions. Experiment 1 shows that an appropriate postlist distractor task does in fact eliminate the "long-term recency effect." This finding supports the assertion that the effect is a product of short-term storage. Experiment 2 demonstrates the benefits and costs of the time-sharing process, relative to standard free recall, for both long-term and short-term storage. The findings support the time-sharing hypothesis. Experiment 3 replicates Experiment 2, with a change in procedure that rules out output interference as a mechanism responsible for the results of Experiment 2. Data are also presented on the development of the adaptation over trials. It is concluded that the adaptation and time-sharing processes need to be included in the dual storage model of short-term storage. PMID- 2319961 TI - Do memorability ratings affect study-time allocation? AB - This research addresses the relation between predicting future memory performance (judgment of learning, or JOL) and subsequent self-paced study-time allocation. The results of three experiments support the main hypotheses: (1) recall increases with increasing JOL, (2) restudy increases JOL accuracy, and (3) study time is related to JOL. This last relation depends on the length of initial presentation time of the items. When the initial exposure trials were short, the most restudy time was allocated to the items judged hard to recall, but when the initial exposure times were long, the most restudy time was allocated to the uncertain items. Items studied longer were recalled equally well (Experiments 1 and 3) or to a lesser extent (Experiment 2) than items studied for a shorter time. It is hypothesized that during study time, subjects refine their JOLs for the items initially less well discriminated. PMID- 2319962 TI - Memorabeatlia: a naturalistic study of long-term memory. AB - Seventy-six undergraduates were given the titles and first lines of Beatles' songs and asked to recall the songs. Seven hundred and four different undergraduates were cued with one line from each of 25 Beatles' songs and asked to recall the title. The probability of recalling a line was best predicted by the number of times a line was repeated in the song and how early the line first appeared in the song. The probability of cuing to the title was best predicted by whether the line shared words with the title. Although the subjects recalled only 21% of the lines, there were very few errors in recall, and the errors rarely violated the rhythmic, poetic, or thematic constraints of the songs. Acting together, these constraints can account for the near verbatim recall observed. Fourteen subjects, who transcribed one song, made fewer and different errors than the subjects who had recalled the song, indicating that the errors in recall were not primarily the result of errors in encoding. PMID- 2319963 TI - Problem solving by reference to rules or previous episodes: the effects of organized training, analogical models, and subsequent complexity of experience. AB - Subjects learned a microcomputer drawing package under different conditions of training organization and practice complexity. Training instructions were presented in either a random or an organized order, and with or without an analogical model of the software package. Practice trial varied in visual and logical complexity. Performance on paper-and-pencil and problem-solving tests was better following the model than following the no-model condition when practice trials were logically complex; the reverse was true when they were logically simple. Performance on the test of problem solving was also better following organized training than following randomly ordered training when practice trials were visually complex; the reverse was true following visually simple practice. We propose that the subjects performed the tasks by engaging in either episode based or rule-based processing, and that performance was optimized when the processing used at encoding and retrieval was the same. The acquisition of skill in solving real problems is explained as procedural compilation. PMID- 2319964 TI - Biomedical applications of mass spectrometry. PMID- 2319965 TI - Negotiators, mediators and arbitrators. PMID- 2319966 TI - Staff nurses: initiators of research. PMID- 2319967 TI - The approaches to learning of specialist physicians. AB - Recent studies have provided information about the approaches to studying and learning used by medical students. However, no published work is available on the approaches of practising doctors. The Adelaide Diagnostic Learning Inventory for Medical Students (ADLIMS) was modified and administered to a random sample of 308 physicians (internists). Generally speaking, physicians seem to have lower scores on surface approach and higher scores on deep approach than students. Level of clinical experience did not appear to influence this finding. However, marked differences were apparent between the approaches adopted by physicians with additional postgraduate academic training and those without. The former had a much stronger tendency to use the more desirable deep approach. The latter seemed to rely more on the less desirable surface approach. Further longitudinal studies will be required to determine whether this difference is attributable to self selection of those who have already developed a deep approach or is causally related to a training in research. Although these findings must be interpreted with caution, some implications are clear. Physicians should become more aware of the way they learn and about the way they teach. Inappropriate patterns of learning may be entrenched during the undergraduate and immediate postgraduate years. If validated, these findings may provide support for the inclusion of research projects in medical school and during specialist training. PMID- 2319968 TI - Assessment of general practice consultations: content validity of a rating scale. AB - A rating scale for assessing clinical performance of trainee general practitioners was constructed based on a contemporary definition of knowledge, skills and attitudes necessary for competent general practice in Australia. The purpose of the rating scale is the provision of feedback to the trainee by both self-evaluation and evaluation by training supervisors. As part of a wider study into the use of videotaped genuine general practice consultations for teaching purposes, the content validity of the scale was examined by comparing the scale data with an open-ended rating form. The comparison resulted in six suggestions which might improve the precision of the instrument, and produce a compact practical scale suitable for the evaluation of general practice consultation. PMID- 2319969 TI - Adverse learning strategy: the Adelaide Diagnostic Learning Inventory and its subscale replicability in a medical student population. AB - The Adelaide Diagnostic Learning Inventory (ADLIMS) is a measure of learning styles and learning pathologies that was designed to investigate the impact of traditional approaches to learning versus problem-based learning and to identify students whose approach to learning tasks predicted poor academic performance. In this study, some important psychometric properties of the ADLIMS were examined, including its factor structure. In this study, factor replicability across samples was argued to provide a more robust and psychologically meaningful factor solution than that which can be obtained using traditional mathematical criteria. The results of the factor analysis did not confirm the presence of the four factor solution earlier reported for the ADLIMS, but did identify three clear factors that had very high replicability. An inspection of the items comprising these three factors showed that factor 1 tapped subjective distress related to poor study habits, lack of motivation to study, and distraction from social activities. Factor 2 tapped distress arising from high achievement expectations that were hampered by superficial or disorganized study habits that did not enable the student to grasp the relationships between concepts and ideas. Factor 3 tapped positive feelings and a sense of satisfaction associated with a problem based approach to the learning of new study material. Although the internal reliability of the ADLIMS subscales met the requirements of a measure to be used in general research such as in the investigation of correlates among groups of medical students, they did not meet the higher requirements of a measure to be used to identify or predict individuals with pathological learning styles. PMID- 2319970 TI - Family and community health in a new medical school. AB - The planning and implementation of a curriculum for a department of family and community health in a new medical school in a developing country presents special problems. The evolution of the programme at Sultan Qaboos University in the Sultanate of Oman is described and discussed. PMID- 2319971 TI - Reasoning strategies and the use of biomedical knowledge by medical students. AB - This paper reports one of a series of studies conducted to investigate the role of biomedical knowledge in clinical reasoning. It was motivated by findings from our earlier studies that demonstrate that when specific basic science information is provided to medical students prior to solving a clinical case, they are unable to use this information in explaining the patient problem. An experiment was designed to investigate the use of biomedical information in the explanation of a clinical problem without any basic science information (spontaneous explanation) and where basic science information was provided after the clinical case (biomedically primed explanation). The results are discussed in the context of a two-stage model of diagnostic reasoning. The first stage is referred to as data driven reasoning, and is characterized by the triggering of inferences from observations in the data to hypotheses. The second stage is designated as predictive reasoning, and is characterized by the generation of inferences driven by hypotheses. The results show that, with the exception of final-year medical students, the use of biomedical information interfered with the data-driven reasoning process. However, it did facilitate the process of predictive reasoning by the students. It is proposed that a sound disease classification scheme is necessary before biomedical knowledge can facilitate both data-driven and predictive reasoning during clinical problem-solving. PMID- 2319972 TI - The application of basic science concepts to clinical problem-solving. AB - This study looks at the relationship between anatomical concepts held by medical students and their clinical application, and develops a testable model of how students use basic science concepts for clinical problem-solving. According to the model, the essential prerequisites to solve a clinical problem using basic science information include the appropriate basic science knowledge, the ability to collect and interpret clinical information, with the key concept being the link that must then be made between clinical data and basic science. A detailed analysis of the individual components of the model should help to clarify and resolve some of the debate about the nature and balance of basic science and clinical education. A neurological diagnostic problem was used to test the assumptions of the model in a group of medical students who had minimal clinical experiences. There was no demonstrable relationship between anatomical knowledge as assessed by conventional tests and the diagnosis. There was a powerful relationship between measures of organization of knowledge and diagnosis, suggesting that the organization and development of concepts is the key to correct diagnosis. The findings have significant implications for assessment purposes and suggest that standard methods as generally practised may not measure the appropriate conceptual development and are not congruent with curricular objectives. Through the examination of its different learning outcome measures, the model may also be used to provide a profile of individual students or classes, which should help teachers and students deal with difficulties that may be experienced in learning to link clinical and basic science concepts. PMID- 2319973 TI - Academic selection criteria and subsequent performance. AB - In this paper we have attempted to determine if there are any aspects of the academic history of a student, prior to admission to the University of Leicester medical course, that correlate with his or her subsequent performance in that course. The analyses presented suggest that a student's overall performance in GCE O- and A-level examinations correlates with subsequent performance at various stages of the medical course. In addition, there is a correlation between performance in the medical course and performance in A-level chemistry and biology but not mathematics, physics or general studies. Students who resat two or more A-level subjects performed at a lower level throughout the course than those with only one or no resits. These results emphasize the importance of academic criteria in the medical student selection process. PMID- 2319974 TI - Smoking among young doctors in Hong Kong: a message to medical educators. AB - A survey was conducted using a self-administered questionnaire to examine the smoking habits, attitudes and practices of 151 doctors in their pre-registration year. The response rate was 88%. Over 80% of the respondents had never smoked. Less than 7% of the men smoked daily and none of the women smoked. Despite a very low smoking rate among the respondents, there were shortcomings in attitudes and practices. The study demonstrated that even in a place like Hong Kong, where the social climate on smoking is already changing in a healthy direction, significant deficiencies in our graduates can still arise if teaching on smoking and its control is undertaken in an uncoordinated manner. We argue that a specific course on the important aspects of smoking and health should be introduced into all undergraduate curricula. This is of special importance in countries where smoking is one the increase and where governmental actions on smoking control are inadequate in comparison with the marketing efforts of powerful multinational tobacco companies. Considering the magnitude of smoking as a global health problem, it is the very least that medical educators should do in combating this pandemic. PMID- 2319976 TI - Sociology and epidemiology in medical education: interpreting the students' response. AB - One morning in June 1988 students at the Royal Free Hospital School of Medicine presented their projects on the final day of the integrated course in sociology and epidemiology. This article describes the event and considers some explanations of what happened, with reference to the published literature on medical education and student culture. PMID- 2319975 TI - The relationship between medical students' locus of control and promotion of breast self-examination. AB - There is general agreement that medical school curricula should involve the teaching of preventive health behaviours. Locus of control is a personality variable that has been associated with health practices and may be associated with tendencies to promote health practices. Few significant relationships have been found correlating health locus of control beliefs with preventive health behaviours. This study investigated the health locus of control of medical students and their tendencies to talk about and teach breast self-examination to women patients. Women students' health locus of control and breast self examination practices were also investigated. The authors conclude that health locus of control has little influence on the tendency of medical students to promote breast self-examination. Other factors apparently have more effect on the student doctor's tendencies to promote health practices. PMID- 2319977 TI - Do medical students get what they expect? A study of possible mismatch between the expectations and experience of medical education and practice. PMID- 2319978 TI - ASME scientific meeting. Association for the Study of Medical Education. Glasgow, 22 September 1989. Abstracts. PMID- 2319979 TI - Research in medical education in the UK. PMID- 2319980 TI - The observation of educational events. AB - This booklet is a guide to using observational research methods in medical and health-care education. Emphasis is given to the role of observation in providing concrete, detailed descriptions of how educational events unfold. It is suggested that observational methods have a valuable contribution to make to our understanding of the structures, functions and 'mechanisms' of educational activities. Three approaches to observation are described: participant observation, interaction analysis and fine-grained sequential analysis. Questions of reliability and validity are addressed. Finally, some sources of further information are given. PMID- 2319981 TI - Informed consent: why bother? PMID- 2319983 TI - [Selective action of calcium antagonists]. PMID- 2319982 TI - [The quality of life is individually determined]. PMID- 2319985 TI - [Drugs for use in the mouth cavity]. PMID- 2319984 TI - [Polyneuropathy in alcoholism and diabetes mellitus]. PMID- 2319986 TI - Advice for travelers. PMID- 2319987 TI - [Thymus hyperplasia in patients with malignant testicular tumors]. AB - Follow-up serial computed tomographic scans of 124 patients treated for testicular cancer with either radiotherapy or retroperitoneal lymphadenectomy alone or in combination with chemotherapy were evaluated. Thymic enlargement occurred three to 20 months after initiation of treatment in 15 of the 124 patients. Thymic enlargement could histopathologically be demonstrated in seven patients as true hyperplasia. One of these seven patients however had evidence of metastatic disease with thymic infiltration by a malignant teratoma. Thus it may be impossible to distinguish benign thymus hyperplasia from tumor-infiltration on the basis of ct information alone and sternotomy may be required. No severe defect of cellular immunity could be found. There is no specific constellation of lymphocytic markers in peripheral blood which could indicate true thymic hyperplasia. PMID- 2319988 TI - [Morphologic study of iliac crest spongiosa in patients with osteoporosis treated with combination therapy of pulsatile administration of parathyroid hormone (1-38 hPTH) and sequential addition of calcitonin nasal spray]. AB - Seven patients with clinically and histologically proven osteoporosis were treated with intermittent doses of parathyroid hormone fragment (hPTH 1-38) in combination with sequential administration of calcitonin by nasal spray. Iliac crest bone biopsies were taken before and after 14 month of treatment. Under treatment we found a moderate increase in the number of osteoclasts without signs of an increased depth of resorption lacunae.No loss of complete trabeculae due to osteoclastic perforation could be demonstrated. In contrast, we found a drastic increase in the layers of osteoblasts covering osteoid tissue by about 100%. Mineralisation defects or endosteal fibrosis were not present in any case. Mean bone volume (BV/TV) increased under treatment from 12.1% to 16.8% (relative increase of 38%) and was due to a thickening of the individual trabeculae in all seven cases. Considering the small number of patients analysed, the described treatment regimen seems to be efficient on a histological point of view. PMID- 2319989 TI - Early maternal-infant contact and neonatal thermoregulation. PMID- 2319990 TI - Reasons for acute care visits and rehospitalizations in very low-birthweight infants. PMID- 2319991 TI - Neonatal nurses and issues in research ethics. PMID- 2319992 TI - Research attitudes, activities, competencies, and interests of NANN members. PMID- 2319993 TI - Between Roger and me. PMID- 2319994 TI - An introduction to neonatal pulmonology. PMID- 2319995 TI - Sources of moral authority: what is right? AB - This variety of rightness--the end, the means, personal moral development--is a reminder of the need for tolerance of several "right" actions. Again, it is a balance between viewpoints, between concern for the individual and the rights of society. Tolerance is a major aspect of American history--tolerance for a variety of religious traditions, tolerance for a variety of ethnic and cultural traditions, tolerance for a variety of interpretations (values) of life and its meaning. We grow up with variety in religious beliefs, values, ethical principles, or theories (ethical pluralism). We also function at varying levels of moral development at different times, which influences our choice of what is right or good in nursing care. The variety of "right" actions can be confusing. We know firsthand the complexity of trying to choose among several morally right actions, one of which is in the best interests of the neonate and his family. This is the challenge of modern neonatal care. This is the challenge of bioethical decision making. This is the challenge for ethical nursing practice. PMID- 2319996 TI - Intravenous immune human serum globulin. PMID- 2319997 TI - Nipple feeding premature infants: a different perspective. PMID- 2319998 TI - Clinical neuropharmacology. PMID- 2319999 TI - Statewide prevalence of illicit drug use by pregnant women--Rhode Island. PMID- 2320000 TI - TATA-dependent and TATA-independent function of the basal and heat shock elements of a human hsp70 promoter. AB - We have characterized the interactions between the TATA element and other sequence elements of a human heat shock protein 70 (hsp70) promoter by a mutational approach. Expression of a distal element of this promoter requires an intact TATA element in human cell lines. The hsp70 TATA element can be functionally replaced for this interaction by TATA elements from the simian virus 40 early and adenovirus EIIa promoters. The TATA element in this promoter therefore both determines the appropriate start site and determines strength by allowing function of the distal element. In contrast, three proximal upstream elements necessary for basal and heat-regulated transcription have no requirement either for a TATA element or for any other proximal element. The behavior of promoters multiply mutant in these proximal elements implies that these elements function independently. We examined the interaction between the heat shock element (HSE) and the TATA element as the distance between the two factor-binding sites was increased. It was necessary to create a mutant HSE with an extended consensus sequence in order for the HSE to function at a distance. Moving this extended HSE 500 bases upstream did not increase its dependence on the TATA element, suggesting that the TATA independence of this element is intrinsic to its function and is not determined by distance from the promoter. PMID- 2320001 TI - Multiple origins of replication in the dihydrofolate reductase amplicons of a methotrexate-resistant chinese hamster cell line. AB - We recently showed that replication initiates in the early S period at two closely spaced zones in the 240-kilobase (kb) dihydrofolate reductase (DHFR) amplicon of the methotrexate-resistant Chinese hamster ovary cell line CHOC 400. Both of these initiation loci (ori-beta and ori-gamma) have previously been cloned in a recombinant cosmid. In this study, we identified a third early-firing initiation locus (ori-alpha) in the much larger DHFR amplicon of the independently isolated methotrexate-resistant Chinese hamster cell line DC3F A3/4K (A3/4K). We describe the molecular cloning of this newly identified locus and demonstrate by chromosomal walking that ori-alpha lies approximately 240 kb upstream from ori-beta. Using overlapping cosmid clones for more than 450 kb of DNA sequence from this region of the DHFR domain, we have monitored the replication pattern of the amplicons in synchronized A3/4K cells. These studies suggest that ori-alpha, ori-beta, and ori-gamma are the only early-firing initiation sites in this 450-kb sequence. In addition, we have been able to roughly localize the termini between ori-alpha and ori-beta and between ori-alpha and the next origin in the 5' direction. Thus, we have now isolated the equivalent of three early-firing replicons (including their origins) from a well characterized chromosomal domain. With these tools, it should be possible to determine those properties that are shared by the origins and termini of different replicons and which are therefore likely to be functionally significant. PMID- 2320002 TI - A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain. AB - The cyclic AMP response element (CRE) is found in many cellular genes regulated by cyclic AMP, and similar elements are present in the early genes of adenovirus that are activated by E1A. The transcription factor CREB has previously been shown to bind this site, and cDNAs for CREB have recently been characterized. We report here the isolation of a cDNA encoding a human DNA-binding protein that also recognizes this motif in cellular and viral promoters. This protein, HB16, displays structural similarity to CREB and to c-Jun and c-Fos, which bind the related 12-O-tetradecanoylphorbol-13-acetate response element (TRE). HB16 contains a highly basic, putative DNA-binding domain and a leucine zipper structure thought to be involved in dimerization. Deletional analysis of HB16 demonstrated that the leucine zipper is required for its interaction with DNA. In addition, HB16 could form a complex with c-Jun but not with c-Fos. Despite its structural similarity to c-Jun and c-Fos and its interaction with c-Jun, HB16 had approximately a 10-fold-lower affinity for the TRE sequence than for the CRE sequence. Although HB16 and CREB both recognized the CRE motif, an extensive binding analysis of HB16 revealed differences in the fine specificity of binding of the two proteins. HB16 mRNA was found at various levels in many human tissues but was most abundant in brain, where its expression was widespread. The existence of more than one CRE-binding protein suggests that the CRE motif could serve multiple regulatory functions. PMID- 2320003 TI - Sequences downstream of the transcription initiation site modulate the activity of the murine dihydrofolate reductase promoter. AB - The murine dihydrofolate reductase gene is regulated by a bidirectional promoter that lacks a TATA box. To identify the DNA sequences required for dihydrofolate reductase transcription, the activities of various templates were determined by in vitro transcription analysis. Our data indicate that sequences both upstream and downstream of the transcription initiation site modulate the activity of the dihydrofolate reductase promoter. We have focused on two regions downstream of the transcription initiation site that are important in determining the overall efficiency of the promoter. Region 1, which included exon 1 and part of intron 1, could stimulate transcription when placed in either orientation in the normal downstream position and when inserted upstream of the transcription start site. This region could also stimulate transcription in trans when the enhancer was physically separate from the promoter. Deletion of region 2, spanning 46 nucleotides of the 5' untranslated region, reduced transcriptional activity by fivefold. DNase I footprinting reactions identified protein-binding sites in both downstream stimulatory regions. Protein bound to two sites in region 1, both of which contain an inverted CCAAT box. The protein-binding site in the 5' untranslated region has extensive homology to binding sites in promoters that both lack (simian virus 40 late) and contain (adenovirus type 2 major late promoter and c-myc) TATA boxes. PMID- 2320004 TI - A novel cis-acting DNA element required for a high level of inducible expression of the rat P-450c gene. AB - A novel cis-acting regulatory element (designated BTE for basic transcription element) was found in the region proximal to the TATA sequence of the P-450c gene by the use of deletion mutations. This DNA element is considered to be involved in the basic transcription of the gene and does not show distinct enhancer activity in itself. Together with the XRE sequence (A. Fujisawa-Sehara, K. Sogawa, M. Yamane, and Y. Fujii-Kuriyama, Nucleic Acids Res. 15:4179-4191, 1987), however, this sequence is required for a high inducible expression of the P-450c gene in response to xenobiotic inducers. The BTE sequence contained the GC box consensus sequence and half of the NF-1-binding consensus or CAT box sequence, but their synthetic oligonucleotides, used as competitors in the gel mobility shift assays, did not compete with the BTE sequence for the binding protein, suggesting that the BTE sequence functions as a different recognition sequence from that for Sp1 or NF-1. Analogous sequences to BTE are found in the region proximal to the TATA sequence of other genes, especially other P-450 genes with different modes of regulation, suggesting that the BTE sequence plays a common regulatory role in basic transcription of genes including a group of the P-450 superfamily. The ubiquitous distribution of nuclear factor(s) binding to this element supports this suggestion. PMID- 2320005 TI - Structure, hormonal regulation, and identification of the interleukin-6- and dexamethasone-responsive element of the rat haptoglobin gene. AB - Hepatic expression of the haptoglobin (Hp) gene in mammalian species is stimulated severalfold during an acute-phase reaction. To identify the molecular mechanism responsible for this regulation, the single-copy rat Hp gene has been isolated. The genomic sequences showed a high degree of homology with the primate Hp gene. Activity of the rat Hp gene was increased in cultured liver cells by interleukin-1 (IL-1), IL-6, and glucocorticoids. The genomic Hp gene sequence spanning from -6500 to +6500, when transiently introduced into human hepatoma (HepG2) cells, directed IL-6- and dexamethasone-stimulated expression of rat Hp mRNA and protein. No response to IL-1 was detected, suggesting that the corresponding regulatory element(s) might lie outside of the tested gene sequences. An IL-6- and dexamethasone-responsive element has been localized to the promoter proximal region -146 to -55. Although the nucleotide sequences of this rat Hp gene region showed substantial divergence from that of the human gene, analysis of sequential 5' and 3' deletion constructs indicated an arrangement of functional IL-6 response elements in the rat Hp promoter sequence comparable to that of the human homolog. The magnitude of IL-6 regulation through the rat Hp gene promoter was severalfold lower than that of the human Hp gene. The reduced activity could be ascribed to a single-base difference in an otherwise conserved sequence corresponding to an active element in the human gene. The IL-6 response of the rat Hp element was improved severalfold by substituting that base with the human nucleotide. PMID- 2320006 TI - DNA binding of heat shock factor to the heat shock element is insufficient for transcriptional activation in murine erythroleukemia cells. AB - The heat shock response is among the most highly conserved examples of regulated gene expression, being present in all cellular organisms. Transcriptional activation of heat shock genes by increased temperature or other cellular stresses is mediated by the binding of a heat shock factor (HSF) to a conserved nucleotide sequence (the heat shock element) present in the promoter of heat inducible genes. Despite the high degree of conservation of this response, embryonic stages of development are characterized by the absence of a heat shock response. Murine erythroleukemia (MEL) cells also lack this response, and we report here a detailed characterization of this defect for one of the most highly conserved of these genes, hsp70. Surprisingly, heat-induced transcriptional activation of this gene does not occur, despite the induction of a protein with the binding specificity of murine HSF. However, the MEL HSF differs slightly in apparent size from the HSF in 3T3 cells, which exhibit a normal heat shock response. These data suggest that activation of mammalian HSF by heat requires at least two separate steps: an alteration of binding activity followed by further modification that activates transcription. MEL cells do not respond to heat shock because they lack the ability to perform this secondary modification. These cells provide a useful system for characterizing heat shock activation in mammals. PMID- 2320007 TI - A novel fluorescence-based system for assaying and separating live cells according to VDJ recombinase activity. AB - We describe two retroviral vector-based recombination substrate systems designed to assay for lymphoid VDJ recombinase activity in cultured cells. Both substrates incorporate a constitutive dominant marker gene (the simian virus promoter-driven neo gene) to allow selection of cells that stably integrate the substrate. Both substrates also include a second marker gene that becomes transcriptionally active only when inverted by a site-specific recombination event between flanking immunoglobulin variable-region gene segments. The first vector, similar in structure to previous retrovirus-based recombination substrates, utilizes the bacterial guanine-xanthine phosphoribosyltransferase gene (gpt) as its activatable marker; detection of inversion (VDJ recombinase activity) involves drug selection and Southern blotting analyses. We have used this vector to make a more extensive and quantitative survey of VDJ recombinase activity in B-lineage cell lines than has previously been performed with stable substrates, and we have compared our results with those of other studies that use transient recombination substrates. In the second vector, the activatable gene is the bacterial beta galactosidase gene (lacZ). Detection for inversional activation of this gene is achieved by a fluorogenic assay, termed FACS-Gal, that detects beta-galactosidase activity in viable cells. The latter assay has the unique advantage of rapidly detecting cells that undergo recombination and also allows viable sorting of cells on the basis of the presence or absence of VDJ recombinase activity. We have used the lacZ vector to rapidly quantitate VDJ recombinase activity in B lineage cell lines and compared the results with those obtained with the gpt vector. We have also used the lacZ vector to isolate variant pre-B-cell lines with low and high levels of VDJ recombinase activity. PMID- 2320008 TI - Three novel brain tropomyosin isoforms are expressed from the rat alpha tropomyosin gene through the use of alternative promoters and alternative RNA processing. AB - cDNA clones encoding three novel tropomyosins, termed TMBr-1, TMBr-2, and TMBr-3, were isolated and characterized from a rat brain cDNA library. All are derived from a single gene, which was previously found to express striated muscle alpha tropomyosin and a number of other tropomyosin isoforms via an alternative splicing mechanism (N. Ruiz-Opazo and B. Nadal-Ginard, J. Biol. Chem. 262:4755 4765, 1987; D. F. Wieczorek, C. W. J. Smith, and B. Nadal-Ginard, Mol. Cell. Biol. 8:679-694, 1988). The derived amino acid sequences revealed that TMBr-1 contains 281 amino acids, TMBr-2 contains 251 amino acids, and TMBr-3 contains 245 amino acids. All three proteins contain a region that is identical to amino acids 81 through 258 of skeletal muscle alpha-tropomyosin. TMBr-1 is identical to striated muscle alpha-tropomyosin from amino acids 1 through 258 but contains a novel COOH-terminal region from amino acids 259 through 281. TMBr-2 and TMBr-3 both contain identical NH2-terminal sequences from amino acids 1 through 44 which were found to be expressed from a novel promoter. TMBr-3 contains the same COOH terminal region as TMBr-1, whereas TMBr-2 contains a second novel COOH-terminal region. The genomic organization of the exons encoding TMBr-1, TMBr-2, and TMBr-3 were determined. These studies revealed a previously uncharacterized promoter located in the internal region of the alpha-TM gene as well as two novel COOH terminal coding exons. The alpha-TM gene is a complex transcription unit containing 15 exons including two alternative promoters, two internal mutually exclusive exon cassettes, and four alternatively spliced 3' exons that encode four different COOH-terminal coding regions. A total of nine distinct mRNAs are known to be expressed from the alpha-TM gene in a cell type-specific manner in tissues such as striated muscle, smooth muscle, kidney, liver, brain, and fibroblasts. The mRNAs encoding TMBr-1, TMBr-2, and TMBr-3 were found to be expressed only in brain tissue, with TMBr-3 being expressed at much greater levels than TMBr-1 and TMBr-2. The individual structural characteristics of each brain alpha-tropomyosin isoform and their possible functions are discussed. PMID- 2320010 TI - HPLC purification of the main allergen of Parietaria judaica pollen. AB - A two-step purification procedure of Par j I from the whole Parietaria judaica pollen extract is described. The first step consisted of gel filtration HPLC using a TSKG 3000 SW column, and 0.1% trifluoroacetic acid as the eluant. By this method, proteins were separated from the highly colored material present in the extract. Then, Par j I-containing fractions were chromatographed on a reversed phase HPLC column (Vydac C4) using an acetonitrile gradient. This second step yielded pure Par j I as assessed by SDS-PAGE and CIE. Previously reported microheterogeneity was still observed, but amino acid analysis of various RP-HPLC fractions suggested that the heterogeneity of Par j I might not be due to changes in its primary structure. Allergenic activity of Par j I was shown to be retained after the purification procedure by several immunochemical techniques. PMID- 2320011 TI - Electron microscopic study of ring-shaped, bivalent hapten, bivalent antidansyl monoclonal antibody complexes with identical variable domains but IgG1, IgG2a and IgG2b constant domains. AB - We have studied by electron microscopy a fascinating series of antidansyl monoclonal antibodies developed by Dangl et al. (Cytometry 2, 395-401, 1982) which have the same variable domain but different constant domains. Three of the four subclasses of mouse IgG were represented, IgG1, IgG2a and IgG2b. Previously, Oi et al. (Nature 307, 136-140, 1984) had examined the flexibilities of these antibodies by time-resolved fluorescence depolarization and found that IgG1 was least flexible, IgG2a was intermediate and IgG2b was the most flexible. In this communication we examine the conformations of circular complexes formed between these antibodies and a bivalent hapten, bis-dansyl cadaverine. The circular complexes were predominantly composed of two antibodies linked into a ring by two bivalent haptens, and are referred to as dimers, since only the antibody molecules are seen with the electron microscope. A few trimers and an occasional tetramer were also present in these preparations. For the least flexible IgG1, almost all (greater than 99%) of the circular dimers were "open-hinge" complexes with a hinge angle between the Fab arms of 100-120 degrees. For the intermediate IgG2a, most of the dimers were "open-hinge" complexes, but a larger percentage, 4 to 5%, had closed hinges with a hinge angle approaching 0 degrees. For the most flexible IgG2b, over 40% of the dimers were "closed-hinge" complexes. A model is proposed to explain these differences based upon orientation of the hapten in the combining site and differences in hinge structure. PMID- 2320009 TI - DNA methylation and demethylation events during meiotic prophase in the mouse testis. AB - The genes encoding three different mammalian testis-specific nuclear chromatin proteins, mouse transition protein 1, mouse protamine 1, and mouse protamine 2, all of which are expressed postmeiotically, are marked by methylation early during spermatogenesis in the mouse. Analysis of DNA from the testes of prepubertal mice and isolated testicular cells revealed that transition protein 1 became progressively less methylated during spermatogenesis, while the two protamines became progressively more methylated; in contrast, the methylation of beta-actin, a gene expressed throughout spermatogenesis, did not change. These findings provide evidence that both de novo methylation and demethylation events are occurring after the completion of DNA replication, during meiotic prophase in the mouse testis. PMID- 2320012 TI - [5th annual meeting of the Society for Pediatric Gastroenterology and Nutrition. 22-24 March 1990, Tubingen. Abstracts]. PMID- 2320013 TI - [Seasonal variations in house dust mite allergens--significance for children with allergy]. AB - Allergenic proteins of the house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae and their major allergens Der p I and Der f I are one of the most significant environmental factors which may facilitate sensitization and allergic airway disease in childhood. In order to measure seasonal variations of mite allergen exposure, we collected mattress dust samples monthly in 13 homes over a period of 1 year. Der p I and Der f I were determined with a sandwich type ELISA. Mite allergen levels were significantly lower from January-June than from July-December (p less than 0.05) which was mostly due to Der p I variations. Only in 6 of the studied homes seasonal variations in mite allergen concentrations according to seasonal variations in outdoor humidity could be observed. In 7 homes mite allergen exposure stayed constant and seemed to depend only on indoor climate factors. PMID- 2320014 TI - [Sensitization to 10 important air-borne allergens in school children]. AB - Sensitization patterns and frequencies for 10 important aeroallergens were tested in a cross-sectional study with 704 schoolchildren (7-16 years) using a standardized skin prick-test method and highly purified immunochemically characterized test-solutions. A ratio of allergen and histamine wheal diameter of 0.5 or more was classified as a positive skin test result. We found a positive skin prick-test to at least one of the aeroallergens in 242 (34.4%) of the children. Among these 39.6% showed monosensitization and 9.8% polysensitization to at least 6 allergens. The most common allergens were grasspollen (19.2%), birchpollen (14.8%), house-dust mite (13.4%), catdander (10.5%) and hazelpollen (9.7%). Monosensitized children reacted mainly to grasspollen and house-dust mite, whereas positive reactions to animal dander and moulds only occurred in polysensitized children more frequently. Reactivity of the tested allergens, measured by the wheal size, was strongest for grasspollen and house-dust mite and the weakest for cladosporium and alternaria. The high prevalence of sensitization to inhalant allergens is an important risk-factor for allergic disease in childhood. PMID- 2320015 TI - [Brachmann-de Lange syndrome in 16 of our patients]. AB - The Brachmann-de Lange-syndrome (Cornelia de Lange-syndrome) belongs to the group of well established multiple congenital anomalies/mental retardation syndromes. The main features are a characteristic dysmorphic face, short stature, defects mainly of the upper limbs and severe psychomotor retardation. A variety of internal anomalies belongs to the non obligatory features of the syndrome. Based on 16 own observations (7 females, 9 males) aged between 1 day and 16 years, we describe the clinical variability of the Brachmann-de Lange-syndrome. Relatively poor prognosis is shown by the fact that up to now 6 of the patients have died. PMID- 2320016 TI - [Acute renal failure with high-dose combination therapy with penicillin G and amoxicillin]. AB - A 3 year old girl was admitted with suspected bacterial meningitis. The patient's history concerning renal and cerebral function and known allergies had been uneventful until that time. 36 h after initiation of a high dose antibiotic therapy with Penicillin G (0.5 Mega IE/kg/day) and Amoxicillin (400 mg/kg/day) macrohematuria and consecutive anuria was observed. Prerenal cardiocirculatory failure, a Schwartz-Bartter-reaction as well as coagulatory failure could be ruled out. There were no symptoms of hypersensitivity. Sonographic examinations of the kidneys and the urinary tract as well as urinanalysis suggested an acute tubular obstruction and papillary necrosis caused by amoxicillin. After changing the antibiotic regimen to chloramphenicol and induction of diuresis by furosemide and dopamine renal failure could be resolved within 39 h. The patient recovered completely. High dose therapy with amoxicillin (greater than 300 mg/kg/day) includes the risk of tubular obstruction due to cristalluria. Solubility of ampicillin in aqueous fluids (6.5 mg/ml at pH 7) should be supported by sufficient diuresis and urine alkalization. PMID- 2320017 TI - [Wolman's disease in an infant]. AB - Wolman's disease is a rare inherited disorder of lipid metabolism in which large amounts of triglycerides and cholesteryl esters accumulate in the visceral organs. The main clinical features of the infantile form of the disease are failure to thrive, vomiting and diarrhoea, hepatosplenomegaly and radiological evidence of calcification of the adrenals. We were able to follow the course of this disease in a female turkish infant. It was first admitted because of a transient swelling within the right angle of mandible, subfebrile temperatures and abdominal distension as well as vomiting at the age of three days. After symptomatic treatment she was discharged home without a specific diagnosis. At the age of 4.5 months she was readmitted with severe hepatosplenomegaly, hypochromic anemia and fever of unknown origin. Calcifications of the adrenals and lymphocytic vacuoles led to the diagnosis of Wolman's disease. Deficiency of acid lipase activity in leucocytes could establish this diagnosis. PMID- 2320018 TI - Abstracts of the First International Congress of Movement Disorders. Washington, D.C., April 25-27, 1990. PMID- 2320019 TI - Deterioration of trapeziometacarpal arthritis due to trigger thumb: a biomechanical evaluation. AB - Patients with trigger thumb and trapeziometacarpal joint arthritis accompanied by swan-neck deformity of their first rays find that their arthritic pain becomes worse whenever their thumbs "catch." Six hands with adduction contracture and arthritis of the trapeziometacarpal joint are studied biomechanically and demonstrate significantly excessive shear forces (p less than 0.01) around their trapeziometacarpal joint relative to six normal hands. Increased pain with deformity suggests aggressive treatment of trigger thumb in cases such as these. PMID- 2320020 TI - Synchronous adenocarcinomas of jejunum and cecum following transverse colon carcinoma. A case study. AB - A case of synchronous primary adenocarcinomas of the small and large bowel in a patient previously treated by transverse colectomy for cancerous polyps is presented. These new primaries were incidental findings during surgery for suspected recurrence of colonic carcinoma. Primary tumors of the small bowel are rare, and the diagnosis of primary adenocarcinoma of small bowel in the presence of primary adenocarcinoma of large bowel requires a high degree of suspicion and may well modify the prognostic outcome if detected early. PMID- 2320022 TI - Male-mediated F1 abnormalities. PMID- 2320021 TI - Bleeding duodenal leiomyoma. PMID- 2320023 TI - The frequency of dominant cataract and recessive specific-locus mutations and mutation mosaics in F1 mice derived from post-spermatogonial treatment with ethylnitrosourea. AB - The frequency of dominant cataract and recessive specific-locus mutations and mutation mosaics was determined in F1 mice derived from post-spermatogonial germ cell stage treatment with 2 X 80, 160 or 250 mg/kg ethylnitrosourea. A total of 5 dominant cataract mutations, 3 dominant cataract mutation mosaics, 1 specific locus mutation and 9 specific-locus mutation mosaics were recovered in 15,542 screened F1 offspring. Results indicate that ethylnitrosourea treatment increases the mutation rate of dominant cataract and recessive specific-locus alleles in post-spermatogonial germ-cell stages of the mouse and that the mutations occur mainly as mosaics. Genetic confirmation of newly induced mutations occurring as mosaics is more problematical for induced recessive alleles than for induced dominant alleles and should be considered when evaluating such mutagenicity results. PMID- 2320024 TI - An examination of respiratory distress and chromosomal abnormalities in the offspring of male mice treated with ethylnitrosourea. AB - A functional defect (respiratory distress), in addition to morphological defects, was induced in the offspring of male ICR mice treated with ethylnitrosourea (ENU) before mating. ENU (100 and 50 micrograms/g) was injected intraperitoneally into adult male ICR mice that were then mated with untreated females. After the cesarian operation on the 18th day of gestation, fetuses were resuscitated. In the apneic fetuses showing respiratory distress, the lung was collapsed and the ductus arteriosus was not closed. The incidence of fetuses showing respiratory distress was significantly increased with the high dose (100 micrograms/g) of ENU, and it was higher after spermatogonial exposure than after postmeiotic exposure. There was no linearity in the dose-response relationship at the lower dose (50 micrograms/g), as was the case with the specific-locus mutation. The frequency per microgram ENU of fetuses showing respiratory distress was 3.7 X 10( 4) for spermatogonial treatment (calculated at a dose of 100 micrograms/g), the value being about 10-20 times higher than that of ordinary mutations in mice. About half of the fetuses showing respiratory distress often had specific anomalies (dwarfism and gigantic thymus), but the remainder showed no morphological changes. Spermatogonial treatment produced a zero or very low incidence of translocations in the meiotic configurations of primary spermatocytes. G-band analysis of the affected F1 fetuses also revealed no visible chromosomal abnormalities (there could be small deletions or inversions) except that trisomy 19 was found in a dwarf fetus. PMID- 2320026 TI - A new dominant neurological mutant induced in the mouse by ethylene oxide. AB - This paper describes a dominant neurological mutation identified among the progeny of a male parent treated with ethylene oxide. The defects observed in the heterozygous mutant include: head tossing, poor limb coordination, and corneal clouding. Both the behavior and ocular manifestations of the mutant syndrome worsen progressively as the affected animals grow older. The mutant animals swim poorly, although they do orient themselves in reference to the surface of the water. Breeding in general is poor. Very small litter sizes result when heterozygous animals of either sex are mated to normal mice. Many male carriers are functionally sterile. All mutant animals had abnormal karyotypes. The original carrier mouse had a translocation between Chromosomes 4 and 17, which was also present in all but one mutant animal. The exceptional animal, which showed all mutant behavioral characteristics, had 41 chromosomes which included two normal 4 and 17 homologs and the small 4(17) translocation chromosome. Karyotypes of unaffected siblings of mutants were normal. Because the small translocation chromosome appears to be inseparably associated with the mutant phenotype, we have named the mutation translocation induced circling mutation symbol, Tim. PMID- 2320025 TI - Reversibility of the effects of chronic paternal exposure to cyclophosphamide on pregnancy outcome in rats. AB - Low-dose chronic treatment of the male rat with the antitumor drug cyclophosphamide causes a time- and dose-dependent increase in pre- and post implantation loss in the untreated females to which he is mated. The objective of the present study was to determine whether such effects are reversed, and if so at what time after cessation of drug treatment. Adult male Sprague-Dawley rats were gavage fed daily, 6 times per week for 9 weeks, with saline (control) or with 1 of 3 doses of cyclophosphamide, 1.4, 3.4 or 5.1 mg/kg/day. After the 9 weeks of treatment and at 2-week intervals thereafter, each male was mated with 2 females in proestrus. The females were caesarian sectioned 20 days later and pregnancy outcome assessed. After 9 weeks of drug treatment, pre-implantation loss increased more than 3-fold from 6% in the control group to 21% in the 5.1 mg/kg/day cyclophosphamide treatment group. Post-implantation loss increased in a dose dependent fashion from 5% in the control group to 74% in the 5.1 mg/kg/day cyclosphosphamide treatment group. Pre-implantation loss rapidly decreased upon cessation of treatment with cyclophosphamide: within 2 weeks it had returned to within the control range. Within just 2 weeks after termination of drug treatment in the 5.1 mg/kg/day cyclophosphamide treatment group, post-implantation loss decreased by half to 44%; it had decreased to 11% by 4 weeks and then was maintained at 4-6% thereafter. In the 3.4 mg/kg/day cyclophosphamide treatment group, post-implantation loss returned to the control range by 4 weeks. Thus, the effects of paternally administered cyclophosphamide on progeny outcome are reversible. The timing of reversal suggests that the effects on pre-implantation loss are due to a drug effect on spermatozoa either in the epididymis or near the time of spermiation while those on post-implantation loss are due to an additional effect on spermatids in the seminiferous tubules. PMID- 2320027 TI - High resolution metrical analysis applied to the assessment of damage associated with induced mutations in the mouse. AB - Morphometric methods were used to investigate variation in the skeletons of 1030 offspring produced from matings of male DBA/2J by female C57BL/6J mice. 751 offspring originated from males that had received a single intraperitoneal injection of ethyl nitrosourea (EtNU) at a dose of 250 mg/kg. The remainder of the mice served as controls. The male parents of the controls were injected only with the buffer used as vehicle for the EtNU. Offspring were obtained for 3 weeks following injection. The treated males were then sterile for about 8 weeks. Immediately after the sterile period another sample of progeny was obtained. In the treated group, litter sizes at birth and weaning were reduced and survival to adulthood was lower. However, none of the differences were statistically significant. The skeletons were evaluated by two independent approaches. The first relied upon gross observation for unusual phenotypic variation, the second on a series of metrical measurement and coordinate data. A considerable amount of variation was recorded by both approaches. Some of the variants were severe but others were mild and perhaps of little or no importance to the health of the mice. The gross observation method produced no evidence for increased mild or severe variants in any group of offspring from the treated mice. The metrical methods also showed no evidence for treatment-related effects in offspring produced during the first 3 weeks of mating. However, in offspring produced after the sterile period, a pronounced, very highly statistically significant increase in all levels of metrical variation was observed. This treatment group revealed both increased variant measures and increased numbers of mice with variant measures. Much of this variation was so slight that it would have escaped notice were it not for the exacting measurements used in the analysis. Our morphometric approach is an analytically powerful tool, suitable for detecting variation in virtually any biological structure that can be measured. If the increased variation reported here is due to induced mutations, the effects would be consistent with that expected from slightly harmful mutations distributed throughout the mouse genome. It is appropriate to consider such effect in connection with genetic risk estimation. PMID- 2320028 TI - Increased incidence of developmental anomalies among descendants of carriers of methylenebisacrylamide-induced balanced reciprocal translocations. AB - N,N'-Methylenebisacrylamide (MBA), a dimer of the monomeric acrylamide, was studied for induction of clastogenic effects in germ cells of male mice. It was found to be effective in inducing dominant-lethal mutations and heritable translocations in maturing sperm. The semisterile translocation carriers and their normal counterparts were used to determine the health impact of transmitted chromosomal rearrangements through anatomical analysis of their immediate descendants in utero. As expected, semisterility resulted primarily from embryonic death during the periimplantation stages presumably caused by sperm segregants with unbalanced chromosome complement fertilizing some of the eggs. Among conceptuses that survived to mid- and late-gestation stages, there was an increased incidence of developmental anomalies including fetal death and phenotypic defects. These anomalies are assumed to be caused by certain types of unbalanced segregants that are compatible with survival beyond the periimplantation period. This class of unbalanced segregants represent in humans a major health problem to the mother and her conceptus. PMID- 2320029 TI - Malformed foetuses and karyotype abnormalities in the offspring of cyclophosphamide and allyl alcohol-treated male rats. AB - Litters sired by male rats chronically treated with cyclophosphamide (CP) or allyl alcohol (AA), were evaluated for the incidence of foetal malformations and karyotype abnormalities. The male rats were also examined for the induction of deleterious effects on various parameters including those involved in reproductive performance. A highly significant and consistent increase in the numbers of malformed foetuses was seen in the litters from CP-treated male rats. Chromosome preparations revealed that a large proportion of the malformed foetuses carried karyotypic abnormalities. These effects were paralleled by a large increase in the number of post-implantation losses without significant differences in several sperm and semen characteristics including sperm abnormalities. No adverse reproductive effects were observed with allyl alcohol treatment. PMID- 2320030 TI - Presumed gene mutations detected in F1 progeny of mouse males treated with ethyl methanesulfonate. PMID- 2320031 TI - Cyclophosphamide in the F0 male rat: physical and behavioral changes in three successive adult generations. PMID- 2320032 TI - Progeny of male rats treated with methadone: physiological and behavioural effects. AB - Male rats were injected with methadone HCl (METH) at 5 mg/kg s.c. for 4 days prior to mating with drug-free females. Offspring resulting from these matings were compared with offspring of drug-free males. The progeny of METH-treated males gained less weight after weaning and had lighter thymuses as adults (but not in infancy). Gonadal weights did not differ in infancy or adulthood, and adrenal weights were heavier in female offspring in adulthood. In adulthood METH offspring were significantly different from controls on all behavioural tests used (open field activity, activity cage activity, passive avoidance latencies, shuttle box avoidances, and rotarod latencies), with the differences frequently affected by test order, days of testing, or sex of offspring. The effects in progeny of METH-treated males in the absence of differences in litter size or neonatal mortality indicate that paternal drug ingestion prior to mating can produce physiological and behavioural changes in progeny that are not dependent on detectable effects on early viability or growth. PMID- 2320033 TI - Tumour incidence in the progeny of male rats exposed to ethylnitrosourea before mating. AB - BDVI male rats were given a single i.p. dose of 80 mg/kg b.w. ethylnitrosourea (ENU), and each rat was then mated at weeks 1, 2, 3, 4 and 5 after treatment with 3 untreated females. A decrease in the fecundity of the treated males was observed, particularly when they were mated 5 weeks after ENU treatment. The average litter size was lower in the treated group, especially for females mated in week 4. No significant differences in pre- or post-weaning mortality were noted between control and treated groups. A slight, non-significant increase in the incidence of brain tumours was observed in the progeny of treated males compared with the controls. The incidence of thyroid tumours was significantly higher in controls but this difference disappeared when adjustment was made for litter effect and intralitter dependence. PMID- 2320035 TI - DNAging. Genetic instability and aging. PMID- 2320034 TI - Tumours and malformations in the adult offspring of cyclophosphamide-treated and control male rats--preliminary communication. AB - Adult offspring aged 52-104 weeks, from male Sprague-Dawley rats treated chronically with cyclophosphamide (CP) were examined for tumours and gross abnormalities. Litter size at birth and at weaning was found to be greatly reduced as a result of paternal CP treatment. No unusual abnormalities were found at post-mortem examination but there was an increase in the incidence of hydronephrosis in offspring from CP-treated males compared with offspring from control males. This increase could have been indirectly caused by CP-treatment through reduced litter size. Histological examination of 26 tumours showed a variety of tumour types in the offspring of CP-treated and control males. Two of the four uterine tumours in offspring from CP-treated males were examined histologically; one was a sarcoma and the other an adenocarcinoma. Although no uterine tumours were found in offspring from control males, it is not clear whether this difference in frequency was treatment-related. The most common tumour site in female offspring from both CP-treated and control males was the mammary gland, and all six of these tumours which were examined histologically were adenofibromas. Abnormal karyotypes were observed in 2 out of 21 offspring showing abnormalities from CP-treated males and none out of 2 offspring with abnormalities from control males. These were not associated with tumours. It was concluded from this limited study that there was no clear evidence of increased tumour incidence in the offspring from CP-treated males. There was an indication that abnormal karyotypes may have been caused by the paternal CP treatment and these abnormalities persisted into adulthood. PMID- 2320036 TI - Age-dependent covalent DNA alterations (I-compounds) in rat liver mitochondrial DNA. AB - Rat liver mitochondrial (mt) DNA was investigated for the presence of I compounds, a recently discovered type of DNA modifications which is detected and measured via 32P-postlabeling. These DNA modifications were previously shown to accumulate in an age-dependent manner in total cellular DNA of various tissues of untreated rodents. In the present work, mt DNA of 1-, 3-, 6-, and 9-month-old female Sprague-Dawley rats was found by 32P-postlabeling also to contain I compounds that increase with age. Most of the I-compounds were identical for mt and nuclear (nu) DNA. A cluster of 2 non-polar I-spots (termed M-compounds) was mitochondria-specific and increased about 8-fold from 1 to 9 months, attaining a RAL value of 44 X 10(-9) or 1 modification in 2.3 X 10(7) DNA nucleotides at 9 months. Quantitative differences between chromatographically identical spots were seen mainly for a low-polarity fraction of I-compounds, which exhibited 2 times higher overall levels in mt DNA versus nu DNA over the age range studied. Total I compound levels increased during this time 6.9- and 5.1-fold in nuclei and mitochondria, respectively. The M-compound level was close to 10% of total mt DNA I-compound levels. M-compounds may conceivably be derived from potentially DNA reactive electron carriers of the mt electron-transport chain, while I-compounds common to both mt and nu DNA presumably originate in extramitochondrial sources. The similarity of mitochondrial and nuclear I-compound profiles and amounts implies possible regulatory mechanisms in I-compound formation and repair. Mt DNA maps showed additional 32P-labeled material which may have been associated with DNA damage caused by oxygen free radicals known to be generated by the mt electron-transport chain. Age-dependent increases of mt DNA modifications are potentially related to mt mutations and may be linked to age-related degenerative changes in mitochondria. PMID- 2320037 TI - Tissue-specific and age-related variations in repetitive sequences of mouse extrachromosomal circular DNAs. AB - Extrachromosomal circular (ecc) DNA was isolated from mouse brain, liver, and heart tissues at different ages. To determine the abundance of repetitive sequences in eccDNAs, preparations were probed for short-interspersed (B1 and B2), long-interspersed (L1), endogenous retroviral-like (IAP), and tandemly repeated satellite sequences (SAT) of the mouse genome. Together these sequence families comprise approximately 15% of the mouse genome. The hybridization results showed that each tissue had a characteristic pattern of repetitive sequence elements in eccDNAs, and the abundance of repetitive sequences changed as a function of age. Repetitive sequences decreased in liver and brain eccDNAs from 1 month to 8 months of age but appeared to remain stable thereafter. In contrast, repetitive sequence families in heart eccDNAs were constant from 1 month to 16 months of age but declined in 24-month-old mice. The present studies indicate that extrachromosomal sequences exhibit greater flexibility than chromosomal sequences. PMID- 2320038 TI - DNA alterations in prostatic adenocarcinoma and benign prostatic hyperplasia: detection by DNA fingerprint analyses. AB - DNA fingerprinting can be utilized to examine a large number of autosomal loci throughout the human genome. Alterations in banding patterns observed on DNA fingerprint analyses reflect DNA alterations ranging from single base changes to complex chromosomal rearrangements. In this report, we describe the application of this technique to prostatic adenocarcinoma (CAP) and benign prostatic hyperplasia (BPH). The majority of CAP cases (12 of 14) displayed alterations in at least 1 of the approximately 30 resolvable bands obtained by fingerprint analyses when compared with DNA obtained from peripheral white blood cells. Unexpectedly, 5 of the 12 cases of BPH examined revealed at least 1 identifiable band alteration in the prostatic tissue. These findings demonstrate the usefulness of fingerprint analyses in the examination of cancer-associated genetic alterations. They also suggest the presence of observable genetic alterations in BPH. PMID- 2320039 TI - Edrophonium responsiveness not necessarily diagnostic of myasthenia gravis. AB - Uneqivocally positive edrophonium tests, both clinically and electrophysiologically, were observed in a classic case of the Lambert-Eaton myasthenic syndrome. A review of the literature revealed that a positive edrophonium response has been reported in a majority of cases of myasthenia gravis (MG) and overlap myasthenic syndrome and in some cases of the Lambert Eaton myasthenic syndrome, botulism, congenital myasthenic syndrome, drug-induced myasthenic syndrome, the Guillain-Barre syndrome, and amyotrophic lateral sclerosis. From this, we conclude that an unequivocally positive edrophonium test alone is not necessarily diagnostic of MG and that the diagnosis of MG should be based on the clinical features together with edrophonium-responsiveness and other laboratory findings. PMID- 2320040 TI - Familial hypertrophic cardiomyopathy and muscle carnitine deficiency. AB - Five members of the same family, along three generations, presented with hypertrophic cardiomyopathy. Neurological examination, muscle strength, electromyography, and serum creatine kinase were normal. Skeletal muscle biopsy showed abnormal lipid accumulation and carnitine deficiency. In three patients the cardiac symptoms and echocardiographic findings improved after treatment with L-carnitine, 3-4 g daily, and a long-chain fatty-acid-free diet. PMID- 2320041 TI - Effect of clenbuterol on normal and denervated muscle growth and contractility. AB - The reported anabolic action of some beta 2 agonists may have clinical applications in certain muscle wasting states. Administration of clenbuterol (2 mg/kg diet for 14 days) to rats resulted in a limited degree of hypertrophy of normal muscles; the effect was more pronounced on fast-twitch muscles than on slow-twitch muscles. The anabolic effect was greatest in denervated muscles, where it was significantly more effective on the slow-twitch type. Clenbuterol significantly improved the contractile properties of denervated slow-twitch muscle, reverting them toward normal, but had little effect on contractile properties of denervated fast-twitch muscle. Such differential effects of clenbuterol must be taken into consideration in the evaluation of any future human intervention study. PMID- 2320042 TI - The expression of myosin light chains and tropomyosin in human muscle biopsies with histochemical type 1 and type 2 fiber deficiency. AB - Two-dimensional gel electrophoresis (2DE) was used to compare the protein composition of human muscle biopsies that were shown by histochemical staining to be deficient in either type 1 or type 2 fibers. Distinct quantitative differences were found in the myofibrillar protein composition of muscle from a 43-year-old woman with proximal limb weakness that showed almost total absence of type 1 fibers and muscle from a 2.5-year-old girl with congenital myopathy in which there was severe lack of type 2 fibers. These data indicate that human type 1 and type 2 muscle fibers express distinct isoforms of myosin light chains and alpha tropomyosin. PMID- 2320043 TI - Hypertrophic mononeuritis clinically presenting with painful legs and moving toes. AB - A 40-year-old woman presented with progressive lower leg pain and spontaneous toe movement. The EMG showed a posterior tibial nerve mononeuropathy and continuous myokymic discharges in posterior tibial-innervated muscles. The MRI revealed a markedly enlarged posterior tibial nerve. Toe movements and myokymia were unaffected by the proximal transection of the lesion but ceased abruptly when the distal end of the fusiform "tumor" was resected, suggesting that spontaneous electrical foci may have been located along the nerve lesion. The markedly enlarged nerve segment contained edematous, swollen fascicles with marked Schwann cell onion-bulb lesions and angiocentric, lymphocytic, and lymphofollicular infiltration. This nerve lesion is an example of a newly recognized entity called hypertrophic mononeuritis. PMID- 2320044 TI - Resealed fiber segments for the study of the pathophysiology of human skeletal muscle. AB - The usefulness of long fiber segments for the study of the pathophysiology of human skeletal muscle was evaluated. Immediately after biopsy, the fiber segments were depolarized. Within 3 hours the cut ends resealed, and if the segments were greater than or equal to 2.5 cm long they regained normal resting membrane potentials (i.e., negative to -80 mV). Miniature endplate potentials, endplate potentials, action potentials, the current-voltage relationship, and the resting intracellular Ca2+ concentration of the resealed fiber segments were similar to those in fibers that were intact from tendon to tendon. In addition, specific properties of intact fibers obtained from patients with various neuromuscular diseases were preserved in the resealed fiber segments prepared from the same patients or patients with the same diseases. These segments are easily obtained as a routine muscle biopsy performed under local anesthesia; they provide valuable preparations for the study of the pathophysiology of human skeletal muscle as well as for in vitro pharmacological tests. PMID- 2320045 TI - The correlation between electrical after-activity and slowed relaxation in myotonia. AB - The correlation between electrical and mechanical after-activity was studied in resealed fiber segments from patients with recessive generalized myotonia (Becker) and in intact fibers from normal muscles which were bathed in 9 anthracene carboxylic acid. The tests were performed in vitro on small bundles of 100 fibers or less. Electromyographic activity and contractile force were measured simultaneously. The relaxation of rested-state twitches and tetani was slowed and accompanied by after-activity in both types of preparations. Often random activity was recorded. In all cases, the contractile force was highly correlated with the electromyographic signs of myotonia. These observations support the hypothesis that electrical after-activity is fully responsible for the slowed relaxation in recessive generalized myotonia. PMID- 2320046 TI - Quantitative EMG in inflammatory myopathy. AB - Fifty-four quantitative electromyographic (EMG) studies were made in 37 patients with inflammatory myopathy (IM) at different points in their clinical course and treatment. All studies were performed in the biceps brachii which varied in clinical strength. Motor unit action potentials (MUAPs) in 45 studies and EMG interference pattern (IP) in 48 studies were recorded using a concentric needle electrode. Macroelectromyographic (Macro-EMG) MUAPs were recorded from 10 patients in 14 studies. MUAP analysis revealed a myopathic pattern (decreased duration and/or area: amplitude ratio) in 69% of studies. IP analysis was more sensitive than MUAP analysis, demonstrating a myopathic pattern in 83% of studies. Macro-EMG MUAP amplitudes were reduced in two studies, minimally increased in one study and normal in the remainder; in 6 (40%) studies, fiber density was slightly increased. Thus, reinnervation does not seem to play an important role in motor unit remodeling in IM. PMID- 2320047 TI - Temperature dependence of the electrical and mechanical responses of the adductor pollicis muscle in humans. AB - Changes at low temperatures of the electrical and mechanical activity of the adductor pollicis muscle were studied in 10 volunteers. Decreasing temperatures resulted in increased amplitude and duration of the negative phase and peak-to peak amplitude of the evoked muscle action potential. Distal latency, electromechanical latency, contraction time, and half-relaxation time were also increased while isometric force, contraction velocity, and relaxation velocity were decreased. The increase of contraction time is greater over the temperature range below 28 degrees C than above 29 degrees C. Skin temperature differs significantly from muscle temperature, showing about 3 degrees C lower values during cooling and up to 4 degrees C higher values during rewarming with radiant heat. PMID- 2320048 TI - Long-duration polyphasic motor unit potentials in myopathies: a quantitative study with pathological correlation. AB - In most myopathies, the duration of motor unit action potentials (MUAPs) is shorter than normal. However, polyphasic MUAPs of duration longer than 20% of the control mean, (long-duration polyphasic potentials, or LDPPs) may be seen. We therefore analyzed the incidence and meaning of LDPPs using quantitative MUAP analysis in 41 patients with different myopathies. The mean duration of all potentials was reduced in only 64% of patients because LDPPs increased the mean. When only simple potentials were considered, however, the mean duration was decreased in 95% of patients. This observation confirms the need to exclude LDPPs when calculating the mean duration of MUAPs for diagnosis. We found LDPPs most often in chronic polymyositis and in one patient with Becker Muscular Dystrophy. LDPPs are attributed to desynchronization of single-fiber potentials within the MUAP and may be due to slow conduction in regenerating muscle fibers. PMID- 2320049 TI - Dantrolene normalizes serum creatine kinase in MDX mice. PMID- 2320050 TI - Extensive homologies between Leishmania donovani chromosomes of markedly different size. AB - The smallest chromosome (230 kb) of the HU3 stock of Leishmania donovani was purified from an orthogonal field alternation (OFAGE) gel, digested with PstI and cloned into the plasmid pUC13. When used to probe Southern blots of OFAGE gels, the cloned sequences recognised one or more large chromosomes in all L. donovani stocks and a small chromosome in HU3 and two additional L. donovani stocks (Khartoum and DD8). These probes recognised a single band on Southern blots of restricted genomic DNA regardless of their homologies to only large or large and small chromosomes. Analysis of lambda EMBL3 genomic clones selected with the same probes suggested that at least 30 kb of DNA was common to large and small chromosomes. Most of the cloned sequences were mapped to the same 50-kb SfiI fragment present in both chromosomes. These data indicate that two or more L. donovani chromosomes of markedly different size on OFAGE gels are extensively homologous. PMID- 2320051 TI - Putrescine N-acetyltransferase in Onchocerca volvulus and Ascaris suum, an enzyme which is involved in polyamine degradation and release of N-acetylputrescine. AB - A novel type of N-acetyltransferase, clearly different from the nuclear and cytosolic polyamine N-acetyltransferases of mammals, was recently found in the intestinal nematode Ascaris suum. The occurrence of this putrescine N-acetylating enzyme has also been noted in the filarial parasite Onchocerca volvulus. The enzyme was partially purified from adults of O. volvulus and A. suum by chromatography on DEAE-cellulose and cadaverine-Sepharose. Substrate specificities of the filarial enzyme resemble those of the N-acetyltransferase from A. suum, with respect to its preference for putrescine and other diamines above polyamines and histones. Additionally, both nematode enzymes acetylated histamine, whereas dopamine and serotonin were not accepted as substrates. The activities of the N-acetyltransferase from O. volvulus and A. suum were potently inhibited by the drug berenil; the type of inhibition was competitive with respect to putrescine. The inhibition constants for berenil were determined as 4.2 and 1.2 microM for the enzymes of O. volvulus and A. suum, the Km values for putrescine were found to be 330 microM and 250 microM, respectively. Putrescine N acetyltransferase is discussed as a regulatory step in the degradation of excessive polyamines via polyamine oxidase to putrescine. At this branching point, putrescine is retained in the cell for de novo synthesis of spermidine and spermine, catabolized via diamine oxidase or acetylated to a suitable transport product for excretion. PMID- 2320052 TI - A nuclear magnetic resonance study of the interactions of the antimalarials chloroquine, quinacrine, quinine and mefloquine with lipids extracted from normal human erythrocytes. AB - The interaction of four antimalarials (chloroquine, quinacrine, mefloquine and quinine) with lipid membranes re-formed from lipid extracts of normal human erythrocytes was studied using 2H- and lipid extracts of normal human erythrocytes was studied using 2H- and 31P-nuclear magnetic resonance (NMR). Inclusion of small amounts of chain-perdeuterated dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylethanolamine (DPPE) as an 2H-NMR probe allowed us to study separately the effects of drugs on PC or PE components of the membranes. Only a very small decrease in the order parameters of the DPPE, but not the DPPC probe, was observed in the presence of chloroquine at a molar ratio of 1:5 of drug to lipid. Addition of quinacrine at the same molar ratio resulted in a small but significant decrease in the order parameters of the lipid side chains; identical effects were obtained with DPPC or DPPE perdeuterated probes. The presence of quinacrine did not induce non-bilayer lipid phases. In contrast, mefloquine and quinine produced a significant disordering of the lipid side chains; the effect was considerably larger with the DPPE probe. In addition, both mefloquine and quinine induced non-bilayer phases of the lipids; mefloquine induced formation of hexagonal and micellar lipid conformation, whereas addition of quinine resulted in the formation of lipid micelles only. The lipid polymorphism induced by either of these drugs was more pronounced when the DPPE component was observed, indicating that the non-bilayer phases were enriched in PE. The results suggest the presence of strong interactions between mefloquine and quinine with lipid bilayers, especially with the PE component.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2320053 TI - Investigation of ecdysteroid excretion by adult Dirofilaria immitis and Brugia pahangi. AB - The excretion of ecdysteroids by the filarial nematode species, Dirofilaria immitis and Brugia pahangi, was examined both in vitro, by the analysis of culture medium, and in vivo, through analysis of serum samples from experimentally infected hosts. There was no evidence of ecdysteroid excretion by intact parasites of either species in vitro. Free ecdysteroids were detected in the serum of ferrets and dogs infected with D. immitis, but concentrations would be at or below the limit of detection in sub-millilitre serum samples. The detection of ecdysteroids in the serum of potential hosts is unlikely to be of value in the diagnosis of filarial infections due to a combination of low titre in the presence of current infection and measurable titre in its absence. Ecdysteroids of dietary origin may contribute to the latter. PMID- 2320054 TI - Glycosphingolipids of Echinococcus multilocularis metacestodes. AB - Neutral and acid glycosphingolipids of Echinococcus multilocularis metacestodes that were obtained after intraperitoneal infection of Meriones unguiculatus have been analyzed by thin layer chromatography. Neutral and acid glycosphingolipids accounted for 95% and 5% of total glycosphingolipids, respectively. 12 different fractions were observed in the neutral glycosphingolipids extracts of the parasite. The most important was a monohexosylceramide fraction accounting for 56.4% of neutral glycosphingolipids. 9 different fractions were detected in gangliosides (acid glycosphingolipids). The fact that these glycosphingolipids were specific to the parasite was established by the analysis of different cell populations of the host. Glycosphingolipids were purified from control and parasite-infected gerbil blood cells as well as from peritoneal exudate cells of healthy gerbils after a non-specific immunostimulation. The chromatograms obtained with these extracts were totally different from the parasite. In addition, parasitosis was found to have no effect on the host blood cell glycosphingolipids. PMID- 2320055 TI - Detoxification reactions of Fasciola hepatica cytosolic glutathione transferases. AB - Acidic/neutral glutathione (GSH) transferase forms have been isolated from Fasciola hepatica by a combination of GSH-affinity chromatography and chromatofocusing. Approximately 10-25% of the activity failed to interact with the GSH-affinity matrix when applied from crude cytosolic preparations. Following partial purification by chromatofocusing this GSH transferase activity did subsequently bind to the affinity matrix. The F. hepatica GSH transferases had catalytic activity with secondary lipid peroxidation products, the latter being possible natural substrates. The enzymes also interacted with a number of hydrophobic ligands including haematin and substituted phenol-based anthelmintics. PMID- 2320056 TI - The specificity of trichomonad cysteine proteinases analysed using fluorogenic substrates and specific inhibitors. AB - The multiple cysteine proteinases of Trichomonas vaginalis and Tritrichomonas foetus, both those retained intracellularly and those released, were separated using gelatin-SDS-PAGE, and their activity towards a range of 15 fluorogenic peptidyl aminomethylcoumarins determined together with their relative sensitivity to inhibitors. Three types of enzyme were apparent in T. vaginalis: (i) an 86-kDa enzyme active only on Z-Arg-Arg-NHMec; (ii) a 54-kDa proteinase which was most active on Z-Phe-Arg-NHMec but also able to hydrolyse N-t-Boc-Val-Leu-Lys-NHMec, Suc-Ala-Phe-Lys-NHMec, H-Pro-Phe-Arg-NHMec and Z-Arg-Arg-NHMec; and (iii) a group of six enzymes which preferentially hydrolysed substrates with bulky residues at the P2 and P3 positions. N-t-Boc-Val-Leu-Lys-NHMec and H-Leu-Val-Tyr-NHMec were the best substrates for the latter group. The 86-kDa proteinase was inactivated by E-64, but only at high concentrations, and was relatively insensitive to the peptidyl diazomethanes. The other proteinases were inhibited by low concentrations of E-64 and by Z-Phe-Ala-CHN2, and to a lesser extent by Z-Phe-Phe CHN2. Differences between the proteinases of T. foetus were also demonstrated. All of them were active on Z-Arg-Arg-NHMec, but their activity towards other substrates varied. Three predominantly extracellular proteinases (25, 27 and 34 kDa), hydrolysed Z-Arg-Arg-NHMec specifically. Other proteinases (apparent Mr of 20,000 and 32,000) hydrolysed a number of other substrates, with the 32-kDa enzyme having greater activity towards N-t-Boc-Val-Leu-Lys-NHMec and H-Leu-Val Tyr-NHMec than towards Z-Arg-Arg-NHMec. At a high concentration (270 microM), E 64 inhibited all of the T. foetus enzymes, but lower concentrations were less effective, with the 18-kDa proteinase being particularly insensitive. Z-Phe-Ala CHN2 and Z-Phe-Phe-CHN2 were relatively poor inhibitors. The results demonstrate that the proteinases of both species are a heterogeneous group with respect to specificity, and have highlighted significant differences between the enzymes of T. vaginalis and T. foetus. The information on the specificities will be useful for assessing the features required in proteinase inhibitors if they are to be of potential value as antitrichomonal agents. PMID- 2320057 TI - Developmentally regulated expression and secretion of a polymorphic antigen by Onchocerca infective-stage larvae. AB - In order to analyse the developmental biology of Onchocerca spp. with a view to identifying molecules with specialised functions, we have devised a novel method for labelling proteins synthesised by larvae during growth in the vectors. Pulse labelling of Onchocerca lienalis by micro-injections of [35S]methionine into blackflies have revealed a major acidic protein of 23 kDa which is developmentally expressed almost exclusively by infective, third-stage larvae. The protein appears to be antigenically conserved between O. lienalis and Onchocerca volvulus, but exhibits size polymorphisms both among species and among individual organisms. It continues to be elaborated after terminal differentiation of the parasite in flies, but not by post-infective larvae entering the phase of development in the vertebrate host. A shift in temperature from 26 degrees C to 37 degrees C triggers secretion of the 23-kDa molecule as a discrete event 24-72 h after transmission. The labelling technique has been successfully employed with filarial species that develop in mosquitoes, and in principle should be widely applicable to the study of endoparasite gene expression within arthropods. PMID- 2320058 TI - Golgi-mediated post-translational processing of secretory acid phosphatase by Leishmania donovani promastigotes. AB - Monensin, an inhibitor of Golgi function, was used to investigate the role of this cell compartment in the glycosylation of Leishmania donovani promastigote secretory acid phosphatase (EC 3.1.3.2). Monensin-treated cells demonstrated morphological changes in the Golgi complex and secreted enzyme with an altered electrophoretic mobility: two discrete bands of approximately 95 and 110 kDa were found, as compared to the heterodisperse nature of the enzyme from untreated controls. Chemical deglycosylation by mild acid hydrolysis resulted in a similar effect on the electrophoretic mobility of purified extracellular enzyme. Acid phosphatase was also treated with N-glycosidase F (EC 3.5.1.52) to remove N linked oligosaccharides. The altered lectin-binding properties of the enzyme after these two treatments demonstrated that an unusual type of galactose containing acid-labile carbohydrate was present in secretory acid phosphatase in addition to the N-linked oligosaccharides. Further, experiments with 32P-labelled enzyme indicated that phosphodiester bonds were the structural component responsible for the sensitivity of this carbohydrate to mild acid hydrolysis. Cumulatively, these results demonstrated that a novel form of Golgi-mediated posttranslational modification had occurred to the secretory acid phosphatase presumably by the addition of an acid-labile phosphoglycan. PMID- 2320059 TI - Leishmania gp63 molecule implicated in cellular adhesion lacks an Arg-Gly-Asp sequence. AB - The parasitic protozoa Leishmania are intracellular pathogens which enter host cells through largely undefined mechanisms. One molecule thought to play an important role in this process is gp63, the major glycoprotein on the surface of the infective promastigote form. We have cloned and analyzed the gp63 gene from Leishmania chagasi, an etiologic agent of acute visceral leishmaniasis. The predicted amino acid sequence is highly homologous to that reported for Leishmania major, with the exception of a 56-amino-acid region. This region in L. major was predicted to contain an arginine-glycine-aspartic acid (RGD) sequence that was subsequently hypothesized to be involved in binding to the host cell. The L. chagasi gene lacks this sequence or indeed any RGD sequence, and further studies failed to confirm the existence of an RGD sequence in the L. major gp63 gene. Binding to the host cell surface must therefore be mediated by other sequences in gp63 or by other components of the Leishmania promastigote. PMID- 2320060 TI - Sequence preference of chloroquine binding to DNA and prevention of Z-DNA formation. AB - Chloroquine is a critically important antimalarial drug and a well known intercalator into DNA. We now show that chloroquine binds more avidly to poly(dG dC).poly(dG-dC) than to other synthetic polynucleotides and that this binding inhibits both salt- and cobalt-induced transitions to Z-DNA. These data are consistent with the possibility that chloroquine's toxicity to malarial parasites is mediated by its effect on DNA. PMID- 2320061 TI - Sequence analysis upstream of the gene encoding the precursor to the major merozoite surface antigens of Plasmodium yoelii. PMID- 2320062 TI - Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies. AB - Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist. Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis. To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis. We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design. Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal. For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects. The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively. Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day). These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis. PMID- 2320063 TI - Effects of pancreatic transplantation on diabetic neuropathy. AB - Reestablishment of the euglycemic state by successful transplantation of the pancreas might halt or reverse diabetic neuropathy. To test this possibility we evaluated neurologic function by clinical examination, nerve conduction studies, and autonomic-function tests in patients with insulin-dependent (Type I) diabetes mellitus before and after successful pancreatic transplantation. Sixty-one patients were studied before and 12 months after transplantation, 27 again after 24 months, and 11 again after 42 months. A control group of patients with Type I diabetes treated with insulin underwent the same studies at similar intervals--48 patients before and after 12 months had elapsed, 21 again after 24 months, and 12 again after 42 months. In the control group, neuropathy tended to worsen during the follow-up period. The scores on the clinical examination indicated increased impairment after 12 months. Composite indexes of the degree of abnormality found on neurophysiologic testing of the function of peripheral motor, sensory, and autonomic nerves indicated decreased autonomic function after 12 months. The examination score and the three index values worsened slightly but not significantly in the patients followed for 24 and 42 months. In contrast, in the patients who had received pancreatic transplants, the neuropathy tended to improve. There was significant improvement in the motor and sensory indexes 12 months after transplantation and in the sensory index 24 months after transplantation. The other measures improved slightly but not significantly at these times, as did all four measures in the patients studied 42 months after transplantation. We conclude that the progression of diabetic polyneuropathy may be halted through the restoration of a euglycemic state by successful pancreatic transplantation. PMID- 2320064 TI - Indicators of prognosis in node-negative breast cancer. AB - Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S phase fraction yielded the most prognostic information, followed by progesterone receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided. PMID- 2320065 TI - The effects of weight loss on the activity and expression of adipose-tissue lipoprotein lipase in very obese humans. AB - Lipoprotein lipase is an enzyme in adipose tissue that hydrolyzes circulating triglycerides and thereby generates the fatty acids used in the synthesis of triglyceride in fat cells. To determine whether the activity and expression of lipoprotein lipase are affected by weight loss, we studied lipoprotein lipase in the adipose tissue of nine very obese subjects before and after a program of weight reduction. The subjects' mean (+/- SEM) initial weight was 136 +/- 7.3 kg, and the body-mass index (weight in kilograms divided by the square of the height in meters) ranged from 33.3 to 52.8 (mean, 43.0 +/- 2.5). Biopsies of adipose tissue were performed before weight loss and after it, when weight had been stable for three months. The weight reduction was achieved by a very-low-calorie diet (mean weight loss, 42.5 +/- 6.8 kg). After weight loss, the level of heparin releasable lipoprotein lipase activity increased in all patients, from 3.8 +/- 1.1 to 7.1 +/- 1.6 neq of free fatty acid released per minute per 10(6) cells (P less than 0.05). In addition, the amount of lipoprotein lipase immunoreactive protein increased from 6.3 +/- 1.7 to 24.4 +/- 6.9 ng per 10(6) cells (P less than 0.05), and there was also an increase in the level of lipoprotein lipase messenger RNA as measured by Northern blotting. There was a strongly positive correlation between the initial body-mass index and the magnitude of the increase in lipoprotein lipase activity (r = 0.80, P less than 0.01) and immunoreactive protein (r = 0.92, P less than 0.01). We conclude that weight loss in very obese subjects leads to the increased activity and expression of lipoprotein lipase, thereby potentially enhancing lipid storage and making further weight loss more difficult. PMID- 2320066 TI - Physicians' responses to financial incentives. Evidence from a for-profit ambulatory care center. AB - Health Stop is a major chain of ambulatory care centers operating for profit. Until 1985 its physicians were paid a flat hourly wage. In the middle of that year, a new compensation plan was instituted to provide doctors with financial incentives to increase revenues. Physicians could earn bonuses the size of which depended on the gross incomes they generated individually. We compared the practice patterns of 15 doctors, each employed full time at a different Health Stop center in the Boston area, in the same winter months before and after the start of the new arrangement. During the periods compared, the physicians increased the number of laboratory tests performed per patient visit by 23 percent and the number of x-ray films per visit by 16 percent. The total charges per month, adjusted for inflation, grew 20 percent, mostly as a result of a 12 percent increase in the average number of patient visits per month. The wages of the seven physicians who regularly earned the bonus rose 19 percent. We conclude that substantial monetary incentives based on individual performance may induce a group of physicians to increase the intensity of their practice, even though not all of them benefit from the incentives. PMID- 2320067 TI - Prenatal test for X-linked severe combined immunodeficiency by analysis of maternal X-chromosome inactivation and linkage analysis. PMID- 2320069 TI - Diabetic autonomic neuropathy. PMID- 2320068 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 15-1990. A 78-year-old woman from the Dominican Republic with chronic diarrhea. PMID- 2320070 TI - Second thoughts about second-look laparotomy in advanced ovarian cancer. PMID- 2320072 TI - Confusion about "negative" studies. PMID- 2320071 TI - Periconceptional use of multivitamins and the prevalence of neural-tube defects. PMID- 2320073 TI - Desmopressin and surgical hemostasis. PMID- 2320074 TI - Carbon monoxide and myocardial ischemia. PMID- 2320075 TI - Blood glucose in suspected hypoglycemia. PMID- 2320076 TI - Treatment of Graves' ophthalmopathy. PMID- 2320077 TI - HIV seropositivity and deliberate weight gain. PMID- 2320078 TI - Genital tumors among men with psoriasis exposed to psoralens and ultraviolet A radiation (PUVA) and ultraviolet B radiation. The Photochemotherapy Follow-up Study. AB - Squamous-cell cancer occurs only rarely on the male genitalia. In a 12.3-year prospective study of 892 men in a cohort of patients with psoriasis who had been treated with oral methoxsalen (8-methoxypsoralen) and ultraviolet A photochemotherapy (PUVA), we identified 14 patients (1.6 percent) with 30 genital neoplasms. The standard morbidity ratio (which was used as a measure of the risk of a genital neoplasm) comparing morbidity among patients treated with PUVA with that expected on the basis of population incidence data was 95.7 (95 percent confidence interval, 43.8 to 181.8) for invasive squamous-cell carcinoma of the penis and scrotum, and 58.8 (26.9 to 111.7) for invasive and in situ penile tumors. In patients exposed to high levels of PUVA, the incidence of invasive squamous-cell carcinoma was 286 times that in the general population and 16.3 times that in patients exposed to low levels (P less than 0.001 for both comparisons). After controlling for the level of exposure to PUVA, we found that patients exposed to high levels of ultraviolet B radiation had a risk of genital tumors 4.6 times higher than that in other patients (95 percent confidence interval, 1.4 to 15.1). The strongly dose-dependent increase in the risk of genital tumors associated with exposure to PUVA and ultraviolet B radiation that we observed makes it prudent for men to use genital protection whenever they are exposed to PUVA or other forms of ultraviolet radiation for therapeutic, recreational, or cosmetic reasons. PMID- 2320079 TI - Mitochondrial myopathy caused by long-term zidovudine therapy. AB - Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary HIV infection, we reviewed the histochemical, immunocytochemical, and electron microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with myopathy (15 of whom had been treated with zidovudine) and compared the findings with the patients' clinical course and response to various therapies. Among the zidovudine-treated patients, the myopathy responded to prednisone in four, to the discontinuation of zidovudine in eight, and to nonsteroidal anti inflammatory drugs in two. Numerous "ragged-red" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the zidovudine-treated patients but not in those from the other patients. The number of these fibers appeared to correlate with the severity of the myopathy. All the patients, regardless of whether they had been treated with zidovudine, had inflammatory myopathy characterized by degenerating fibers, cytoplasmic bodies, and endomysial infiltrates consisting of CD8+ cells (mean +/- SD, 60.7 +/- 6.4 percent) and macrophages (39.2 +/- 6.4 percent) associated with Class I major histocompatibility complex (MHC-I) antigens (HLA-A, -B, and -C antigens) in the muscle fibers. The numbers and percentages of CD8+ cells and macrophages were similar in both the zidovudine-treated and the untreated HIV positive patients. Specimens obtained on repeat muscle biopsy from two patients in whom the myopathy responded to the discontinuation of zidovudine showed remarkable histologic improvement. We conclude that long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which coexists with a T-cell mediated inflammatory myopathy that is restricted to MHC-I antigen, and is indistinguishable from the myopathy associated with primary HIV infection or polymyositis in HIV-seronegative patients. PMID- 2320080 TI - Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. AB - Tumors from patients with humoral hypercalcemia of cancer produce a parathyroid hormone-related protein (PTHRP). We have developed two region-specific immunoassays capable of measuring PTHRP in plasma: an immunoradiometric assay directed toward PTHRP amino acid sequence 1 to 74 and a radioimmunoassay directed toward PTHRP amino acid sequence 109 to 138. Sixty normal subjects had low or undetectable plasma PTHRP (1 to 74) concentrations (mean, 1.9 pmol per liter) and undetectable PTHRP (109 to 138) concentrations (less than 2.0 pmol per liter). Patients with humoral hypercalcemia of cancer (n = 30) had elevated levels of both PTHRP (1 to 74) (mean, 20.9 pmol per liter) and PTHRP (109 to 138) (mean, 23.9 pmol per liter). The plasma concentrations of immunoreactive PTHRP correlated with the levels of urinary cyclic AMP excreted; in some patients, the concentrations decreased after the tumors were resected. Patients with chronic renal failure (n = 15) had plasma PTHRP (1 to 74) concentrations similar to those in the normal subjects, but their plasma PTHRP (109 to 138) concentrations were elevated (mean, 29.6 pmol per liter). The levels of both peptides were normal in patients with hyperparathyroidism and those with hypercalcemia due to various other causes. Breast milk contained high concentrations of PTHRP. An anti-PTHRP (1 to 36) immunoaffinity column failed to extract PTHRP (109 to 138) immunoactivity from plasma, suggesting that the C-terminal region circulates as a separate peptide. We conclude that plasma PTHRP concentrations are high in the majority of patients with cancer-associated hypercalcemia and that the circulating forms of PTHRP in such patients include both a large N-terminal (1 to 74) peptide and a C-terminal (109 to 138) peptide. Measuring the concentrations of PTHRPs may be useful in the differential diagnosis of hypercalcemia. PMID- 2320081 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-1990. A 57-year-old woman with a thalamic lesion and pulmonary arteriovenous fistulas. PMID- 2320082 TI - Phototherapy and photochemotherapy. PMID- 2320084 TI - When a house officer gets AIDS. PMID- 2320083 TI - Parathyroid hormone-related peptide in sickness and in health. PMID- 2320085 TI - Parathyroid hormone-related protein and hypercalcemia secondary to massive mammary hyperplasia. PMID- 2320086 TI - Erythropoietin and preoperative blood donation. PMID- 2320087 TI - Serum lithium during treatment of bipolar disorder. PMID- 2320088 TI - A plea for CPR equipment in public places. PMID- 2320089 TI - Discrepancy between medical decisions for individual patients and for groups. PMID- 2320090 TI - Helping bereaved parents. PMID- 2320091 TI - Paper nurses versus people nurses. PMID- 2320092 TI - Mbane. African lightning. PMID- 2320093 TI - Clinical nursing. AB - Today clinical nursing in South Africa is at the crossroads. Many of its best practitioners are lured into management and education, where direct patient contact may be minimal or non-existent. Two reasons for this brain-drain are expounded. Furthermore, a more satisfactory and challenging career structure in clinical nursing is suggested as one possible solution. The educational preparation of nurse clinicians in essential life-skills also needs further attention. The Biomatrix approach is modified and applied to nursing education in an attempt to explain the need for nursing students to learn within a framework that generates self-actualisation, competence and adequate feedback. PMID- 2320094 TI - Experiencing trade unions abroad. PMID- 2320095 TI - Trauma and emergency nursing. PMID- 2320097 TI - [The power and powerlessness of medical science]. PMID- 2320096 TI - Congenital abnormalities. PMID- 2320098 TI - Community nursing looks ahead. PMID- 2320099 TI - Demand for more AIDS protection in the U.S. PMID- 2320100 TI - More AIDS turmoil. PMID- 2320101 TI - Aging. Setting the memory norm. PMID- 2320102 TI - US shuts down monkey trade. PMID- 2320103 TI - Genetic engineering. New european release rules ratified. PMID- 2320105 TI - Influenza according to Hoyle. PMID- 2320104 TI - Harvard legislates on conflict. PMID- 2320106 TI - Growth factors. Growth without inflation. PMID- 2320107 TI - Developmental biology. Compartments in vertebrates? PMID- 2320108 TI - Membranes. Violating the one-way system. PMID- 2320109 TI - A sodium-potassium switch in the formation of four-stranded G4-DNA. AB - Single-stranded complex guanine-rich DNA sequences from chromosomal telomeres and elsewhere can associate to form stable parallel four-stranded structures termed G4-DNA by a process that is anomalously dependent on the particular alkali metal cation that is present. The anomaly, which is not found in the formation of G4 DNA by oligonucleotides containing short, single runs of three or more guanines, is caused by potassium cations excessively stabilizing fold-back intermediate structures, or pathway by-products. PMID- 2320110 TI - Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions. AB - In the chick embryo hindbrain, morphological segmentation into rhombomeres is matched by metameric patterns of early neuronal differentiation and axonogenesis. Boundaries between rhombomeres coincide with boundaries of expression of murine regulatory genes. By clonal analysis using intracellular marking, we show here that the rhombomere boundaries are partitions across which cells do not move. When a parent cell is marked before the appearance of rhombomere boundaries, the resulting clone is able to spread into the neighbouring rhombomere. When marked after boundary appearance, the clone still expands freely within the rhombomere of origin, but it is now restricted at the boundaries. Rhombomeres in the chick embryo thus behave like polyclonal units, raising the possibility that they are analogous to the compartments of insects. PMID- 2320111 TI - Identification and characterization of an inhibitor of haemopoietic stem cell proliferation. AB - The haemopoietic system has three main compartments: multi-potential stem cells, intermediate stage progenitor cells and mature cells. The availability of simple reproducible culture systems has made possible the characterization and purification of regulators of the progenitor cells, including colony-stimulating factors and interleukins. In contrast, our knowledge of the regulators involved in the control of stem cell proliferation is limited. The steady-state quiescent status of the haemopoietic stem cell compartment is thought to be controlled by locally acting regulatory elements present in the stromal microenvironment, but their purification has been hampered by the lack of suitable culture systems. We have recently developed a novel in vitro colony assay that detects a primitive cell (CFU-A) which has similar proliferative characteristics, in normal and regenerating bone marrow, to the CFU-S (haemopoietic stem cells, as defined by the spleen colony assay) and which responds to CFU-S-specific proliferation regulators. We have now used this assay to purify to homogeneity a macrophage derived reversible inhibitor of haemopoietic stem cell proliferation (stem cell inhibitor, SCI). Antibody inhibition and sequence data indicate that SCI is identical to a previously described cytokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and that SCI/MIP-1 alpha is functionally and antigenically identical to the CFU-S inhibitory activity obtained from primary cultures of normal bone marrow cells. The biological activities of SCI/MIP-1 alpha suggest that it is a primary negative regulator of stem cell proliferation and that it has important therapeutic applications in protecting haemopoietic stem cells from damage during cytotoxic therapies for cancer. PMID- 2320112 TI - Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages. AB - The nuclear factor GF-1 (also known as NF-E1, Eryf-1; refs 1-3 respectively) is important in regulation of the transcription of globin and other genes that are specifically expressed in erythroid cells. We have previously shown that GF-1 of both mouse and human origin is a 413-amino-acid polypeptide with two novel zinc finger domains whose expression is restricted to erythroid cells. Using in situ hybridization of mouse bone marrow cells and northern blot analysis of purified cell populations and permanent cell lines, we show here that GF-1 is expressed in two other hematopoietic lineages, megakaryocytes and bone marrow-derived mast cells. Our findings are consistent with results from hematopoietic progenitor culture which suggest a relationship between erythroid, megakaryocytic and mast cell lineages, and imply that GF-1 is expressed in committed multipotential cells and their progeny. Hence, the mere presence of this transcription factor is unlikely to be sufficient to programme differentiation of a single haematopoietic lineage. GF-1 may regulate the transcription of not only erythroid genes, but also many genes characteristic of megakaryocytes and mast cells, or genes shared among these lineages. PMID- 2320113 TI - Megakaryocytic and erythrocytic lineages share specific transcription factors. AB - Erythroid-specific genes contain binding sites for NF-E1 (also called GF-1 and Eryf-1; refs 1-3 respectively), the principal DNA-binding protein of the erythrocytic lineage. NF-E1 expression seems to be restricted to the erythrocytic lineage. A closely related (if not identical) protein is found in both a human megakaryocytic cell line and purified human megakaryocytes; it binds to promoter regions of two megakaryocytic-specific genes. The binding sites and partial proteolysis profile of this protein are indistinguishable from those of the erythroid protein; also, NF-E1 messenger RNA is the same size in both the megakaryocytic and erythroid cell lines. Furthermore, point mutations that abolish binding of NF-E1 result in a 70% decrease in the transcriptional activity of a megakaryocytic-specific promoter. We also find that NF-E2, another trans acting factor of the erythrocytic lineage, is present in megakaryocytes. Transcriptional effects in both lineages might then be mediated in part by the same specific trans-acting factors. Our data strengthen the idea of a close association between the erythrocytic and the megakaryocytic lineages and could also explain the expression of markers specific to the erythrocytic and megakaryocytic lineages in most erythroblastic and megakaryoblastic permanent cell lines. PMID- 2320114 TI - Antibodies produced in plants. PMID- 2320115 TI - Abortion from a hat. PMID- 2320116 TI - US takes the offensive on animal research. PMID- 2320118 TI - Leading biotechnology companies quit the IBA. PMID- 2320117 TI - Cancer risks. War is unhealthy, US finds. PMID- 2320119 TI - Health risks. Radiation research revamped. PMID- 2320120 TI - Genetic engineering. Transfer study expands. PMID- 2320121 TI - Superficial microwave heating. PMID- 2320122 TI - Irradiated cells. PMID- 2320123 TI - Collagenous proteins multiply. PMID- 2320124 TI - Thaumatin not proteolytic. PMID- 2320125 TI - Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3. AB - SPINAL muscular atrophy (SMA) describes a group of heritable degenerative diseases that selectively affect the alpha-motor neuron. Childhood-onset SMAs rank second in frequency to cystic fibrosis among autosomal recessive disorders, and are the leading cause of heritable infant mortality. Predictions that genetic heterogeneity underlies the differences between types of SMA, together with the aggressive nature of the most-severe infantile form, make linkage analysis of SMA potentially complex. We have now analysed 13 clinically heterogeneous SMA families. We find that 'chronic' childhood-onset SMA (including intermediate SMA or SMA type II, and Kugelberg-Welander or SMA type III) is genetically homogeneous, mapping to chromosomal region 5q11.2-13.3. PMID- 2320126 TI - Imprinting of acetylcholine receptor messenger RNA accumulation in mammalian neuromuscular synapses. AB - IN mammalian muscle, the subunit composition of the nicotinic acetylcholine receptor (AChR) and the distribution of AChRs along the fibre are developmentally regulated. In fetal muscle, AChRs are distributed over the entire fibre length whereas in adult fibres they are concentrated at the end-plate. We have used in situ hybridization techniques to measure the development of the synaptic localization of the messenger RNAs (mRNAs) encoding the alpha-subunit and the epsilon-subunit of the rat muscle AChR. The alpha-subunit is present in both fetal and adult muscle, whereas the epsilon-subunit appears postnatally and specifies the mature AChR subtype. The synaptic localization of alpha-subunit mRNA in adult fibres may arise from the selective down-regulation of constitutively expressed mRNA from extrasynaptic fibre segments. In contrast, epsilon-subunit mRNA appears locally at the site of neuromuscular contact and its accumulation at the end-plate is not dependent on the continued presence of the nerve terminal very early during synapse formation. This suggests that epsilon subunit mRNA expression is induced locally via a signal which is restricted to the end-plate region and is dependent on the presence of the nerve only during a short period of early neuromuscular contact. Evidently, several mechanisms operate to confine AChR mRNAs to the adult end-plate region, and the levels of alpha-subunit and epsilon-subunit mRNAs depend on these mechanisms to differing degrees. PMID- 2320127 TI - Regulation of mitosis by cyclic accumulation of p80cdc25 mitotic inducer in fission yeast. AB - The coordination of somatic cell division with cell size must be accomplished by the accumulation of mitotic inducers or the dilution, in the course of cell growth, of mitotic inhibitors. In fission yeast (Schizosaccharomyces pombe), cell size at mitosis is determined by expression of the cdc25+ and nim1+ inducer genes and of the inhibitor gene wee1+, which between them regulate the M-phase protein kinase p34cdc2. We now report that both the phosphoprotein product of cdc25+ (p80cdc25, with apparent relative molecular mass 80,000) and the corresponding messenger RNA increase in concentration as cells proceed through interphase, peaking at mitosis. We propose that the cell-cycle timing of mitosis in somatic cells is regulated by the cyclic accumulation of the cdc25 mitotic inducer, which on reaching a critical level results in activation of p34cdc2 protein kinase. Accumulation of this inducer could play a part in coordinating cell division with growth. PMID- 2320129 TI - Deutsche Gesellschaft fur Pharmakologie und Toxikologie. Abstracts of the 31st spring meeting. 13-16 March 1990, Mainz. PMID- 2320128 TI - Sequencing and expression of complementary DNA for the general transcription factor BTF3. AB - The initiation of transcription of eukaryotic genes involves the ordered assembly of a multiprotein complex on proximal promoter elements such as the TATA box. In addition to RNA polymerase II (otherwise RNA pol II, RNA polymerase B), four general transcription factors are required for initiation of transcription: BTF1 (also referred to as TFIID) which has recently been cloned from yeast, BTF2, BTF3 and STF. The first step in assembly of the initiation complex is the stable binding of BTF1 to the TATA box, which is facilitated by STF. Neither BTF2 nor BTF3 bind directly to the promoter proximal elements, but BTF3 can form a stable complex with RNA pol II. We recently purified BTF3, which is a protein of relative molecular mass 27,000, but further studies have been hampered by its low abundance in cells. On the basis of sequences from peptides of BTF3, we have now cloned two complementary DNAs, one for a protein (BTF3a) with all the characteristics of purified BTF3, and one for a shorter protein (BTF3b) lacking the first 44 residues of BTF3a and which is transcriptionally inactive, despite its ability to bind RNA pol II. PMID- 2320130 TI - HCFA oversight not a reason for panic: a proposed approach. PMID- 2320131 TI - Regain OPTN's policy--making authority through transplant act. Organ Procurement Transplant Network. PMID- 2320132 TI - Method II reimbursement continues to raise questions for providers, patients. PMID- 2320133 TI - What are the real costs for staff-assisted home dialysis? PMID- 2320134 TI - Reform needed, but not at the expense of patients' quality of life. PMID- 2320135 TI - HCFA: failing to acknowledge the unique characteristics of the ESRD patient. PMID- 2320136 TI - Basic research in renal mechanisms and pathophysiology of hypertension. PMID- 2320137 TI - Diagnosis and treatment of hypertension in the elderly. PMID- 2320138 TI - Why not a reasonable approach to EPO? PMID- 2320139 TI - RPA: a more objective voice needed in ESRD rate-setting. PMID- 2320140 TI - What the AOPO survey results mean. Association of Organ Procurement Organizations. PMID- 2320141 TI - U.S. donor procurement in 1989: some song, third verse. PMID- 2320142 TI - [Neuroarthropathy of the diabetic foot]. PMID- 2320143 TI - [Pop, rock, walk and buzz; modern noise and hearing]. PMID- 2320144 TI - [Clinimetrics in traumatology]. PMID- 2320145 TI - [The treatment of recurrent inguinal hernia]. AB - Between 1980 and 1987 a total of 163 patients were operated for unilateral recurrent inguinal hernia in the University Hospital Dijkzigt. Various factors were analysed statistically with the log rank test for their prognostic value to predict repeat recurrence. Lower repeat recurrence rates were found with increase of age (p = 0.05) and time passed since the previous hernia operation (p = 0.001). Using the actuarial method of analysis the total cumulative repeat recurrence rate after five years was 23%. PMID- 2320146 TI - [Current treatment of bilateral recurrent inguinal hernias using preperitoneal Marlex mesh prosthesis]. AB - In the literature recurrence after operation for a recurrent inguinal hernia varies from 3 to 36%. For bilateral recurrent hernia the risk of recurrence is even higher. The results of a preperitoneal Marlex prosthesis in these patients are excellent. After this procedure we saw no new recurrences in 35 patients with 70 recurrent hernias. There was no surgical mortality; in 2 patients superficial infection occurred and there were 4 inguinal haematomas. The preperitoneal Marlex prosthesis appears to be the ideal solution for bilateral recurrent inguinal hernias. PMID- 2320147 TI - [Congenital laryngeal stenosis; a rare cause of dyspnea in the newborn infant]. AB - Congenital laryngeal obstruction is a rare but serious cause of severe, often fatal, post partum asphyxia. The condition should be recognized and in most cases an artificial airway has to be established immediately because hypoxia allows little time for extensive evaluation. Thereafter a further diagnostic procedure by means of laryngobronchoscopy and contrast laryngography should be performed. The clinical picture of two cases with a congenital laryngeal stenosis is described and the initial therapeutic approach is discussed. PMID- 2320148 TI - [EC-legislation and health care; various relevant aspects]. PMID- 2320149 TI - [Pharmacology and pharmacotherapy in Japan]. PMID- 2320150 TI - [Blow-out fractures of the orbit]. PMID- 2320151 TI - [Anaphylaxis following administration of polidocanol]. PMID- 2320152 TI - [Pain originating from the peripheral nervous system]. PMID- 2320153 TI - [Aspiration and sclerosing of a scrotal cyst; a simple ambulatory procedure]. PMID- 2320154 TI - [Restless legs syndrome]. PMID- 2320155 TI - [As strong as iron?]. PMID- 2320156 TI - [Heart infarct in The Netherlands; decreased mortality, increased morbidity and more intervention]. PMID- 2320157 TI - [Prevention in bacterial meningitis]. PMID- 2320158 TI - [Dutch research concerning bacterial meningitis; implications for chemoprophylaxis]. PMID- 2320159 TI - [Basic concepts in statistics. IX. Standardization]. PMID- 2320160 TI - [Observations on the current status concerning the epidemic of acute myocardial infarction]. AB - After the mortality from acute myocardial infarction had reached its peak in 1972, a decrease started which by now, taking into account the increase and the greying of the population, already amounts to 33%. Nevertheless, in 1987 as many as 19,168 deaths were still recorded. When after World War II the mortality rose, it was found that the victims included a growing proportion of younger persons. Currently, however, the decrease of mortality in general is most pronounced among the younger age groups. Among the patients treated in hospital, mortality shows an evenly distributed decrease. The admission rates from the populations of commuter municipalities and from rural areas are relatively low, those from medium-sized municipalities with an urban character, relatively high. PMID- 2320161 TI - [Regional differences in mortality from ischemic heart disease]. AB - The geographical distribution of mortality from ischaemic heart disease in the Netherlands has changed dramatically since 1950. In 1950-1954 mortality was highest in high-income, urbanized areas, in 1980-1984 the reverse was true. This development resembles the one observed in the United States of America. The changes in geographical distribution cannot be attributed to differences in cause of-death certification. The change in the association with income and the association between mortality and a number of ischaemic heart disease risk factors found in 1970-1974, suggest that at least part of the explanation is a change in the geographical distribution of risk factors. PMID- 2320162 TI - [Renal artery reconstruction for renovascular hypertension]. AB - Between 1959 and 1983, 172 patients were treated for hypertension by reconstruction of a renal artery. Reconstruction was preferably performed with autologous material. In a selected group of 29 patients with lesions in the distal renal artery or the hilar branches, an extracorporeal reconstruction with autotransplantation was performed. After a mean follow-up of 8.4 years the hypertension was cured or improved in 82% of the patients. In patients with an arteriosclerotic renal artery stenosis this result was favourably influenced by a short duration of hypertension before the operation. Their life expectancy after the operation was clearly favourably influenced by a beneficial blood pressure response even if arteriosclerotic lesions of coronary arteries, extracranial vessels and/or peripheral vessels were present before the renovascular operation. In selected patients, renal artery reconstruction for treatment of hypertension yields excellent short-term and long-term results, not only with regard to the blood pressure response but also with respect to the patients' life expectancy. PMID- 2320163 TI - [Meningococcal disease in the winter season 1988-1989]. AB - We describe the 304 cases of meningococcal disease notified from week 45 of 1988 and up to week 21 of 1989, and compare these data with those for 1966, the year of the last epidemic in The Netherlands. During the epidemic the interval between the first day of illness and the moment of reporting shortened. PMID- 2320164 TI - [Abuse of anticholinergic agents]. PMID- 2320165 TI - [Dioxins, environment and health]. PMID- 2320166 TI - [Performance scales in oncology]. PMID- 2320167 TI - [Zellweger syndrome and other peroxisomal disorders: II. (Bio)chemical characteristics of a recently discovered group of diseases]. PMID- 2320168 TI - [The course of benign stomach ulcer; results of a follow-up study]. AB - A follow-up investigation was conducted in 112 patients in whom a benign gastric ulcer had been found endoscopically between 1978 and 1984. Nine patients had been operated upon, mainly in the earlier years. Out of 65 patients ultimately selected for the study 38 underwent gastroscopy and 35 could be evaluated. Of these 21 (60%) had complaints and another 60% used intermittent or continuous medication because of complaints referred to the stomach. In 15 patients erosions (4) or benign gastric ulcers (11) were found. In all patients in whom it was looked for Campylobacter pylori was found in the gastric mucosa. The benign gastric ulcer is a chronic, recurrent affection. We did not find a large proportion of asymptomatic recurrent ulcers. Many patients continue to use drugs. The complaints in patients with mucosal lesions are often atypical. PMID- 2320169 TI - [Declining trend in gonorrhea in The Netherlands; significance for the AIDS epidemic?]. AB - Since 1981, the notified incidence of gonorrhoea has been decreasing in The Netherlands, thus preceding the onset of the AIDS epidemic. The declining trend of gonorrhoea and its underlying reasons are investigated. The reporting patterns may be influenced not only by the disease incidence but by other factors as well. Therefore the national notification gonorrhoea data over the period 1976-1988 are analysed in conjunction with detailed data from the two sexually transmitted diseases (STD) clinics in Amsterdam. Since 1983 the decline in gonorrhoea has been further reinforced by a dramatic decrease in gonorrhoea among homo/bisexual men, presumably as a result of behavioural changes because of AIDS. There is less evidence of massive behavioural changes among heterosexuals. The incidence of repeat infection among the gonorrhoea population in Amsterdam increases and may suggest that sexually highly active individuals continue to put themselves at risk of STDs, despite the educational campaigns with respect to the AIDS epidemic. PMID- 2320170 TI - [Vitamin B12 (cobalamin)-deficiency in the elderly]. AB - In order to determine the relevance of low vitamin B12 concentration in elderly persons (greater than 65 years), serum vitamin B12 levels were measured in 292 consecutive patients upon their admission to a geriatric ward. Eighty (27%) of them were anaemic (haemoglobin less than or equal to 7.14 mmol/l). The vitamin B12 concentration was not statistically different between males and females, nor between the anaemic and non-anaemic groups. Twenty-two patients (7.5%) had a low vitamin B12 level; of these, 10 had a haemoglobin concentration higher than 7.14 mmol/l and a mean corpuscular volume lower than 98 fl. In addition, serum vitamin B12 levels were also measured in 178 consecutive anaemic patients hospitalized in the same ward. Seventeen (9.5%) of them had a vitamin B12 deficiency although in 11 the MCV was lower than 98 fl. Hypersegmented polymorphonuclear leukocytes were rarely observed in the peripheral blood smear. Pernicious anaemia could only be diagnosed in 1 patient. Serum vitamin B12 estimation may be necessary to detect vitamin B12 deficiency but a low level requires additional diagnostic investigation. PMID- 2320171 TI - [Influenza 1989/'90: A-H3N2 virus related to the vaccine virus]. PMID- 2320172 TI - [Is the end in sight for the AIDS epidemic in The Netherlands?]. PMID- 2320173 TI - [Nutritional intervention in occupational medicine]. PMID- 2320174 TI - [The unfamiliarity of occupational medicine]. PMID- 2320175 TI - [An unexpected complication of exercise test studies]. PMID- 2320176 TI - The subrenal capsule assay in immunocompetent mice--the inevitable role of histopathology in assessment of this method as a tool determining tumor sensitivity to cytostatic drugs. AB - The subrenal capsule assay (SRC) in immunocompetent mice became one of commonly used approaches to evaluating the efficiency of cytostatic therapy. A comparison of the classical macroscopic evaluation according to the Bogden diagram with results of the histopathologic examination in 118 mice with implanted Yoshida sarcoma or human rectal adenocarcinoma demonstrated the tumor to be present to different extent only in 26 out of 50 macroscopically positive cases and, on the other hand, it was found in 3 out of 68 macroscopically negative animals. Histological changes in these cases, as well as a study of the dynamics of the development of histopathologic changes after tumor implantation and the changes after implantation of inert materials demonstrated that the resorptive and reparative granuloma, originating in immunocompetent mice under the renal capsule after implanting the tumor or other materials, simulates perfectly the growth of the tumor infiltrate. For this reason we consider this method in immunocompetent mice as unreliable when there is no parallel histological examination. PMID- 2320177 TI - An experimental immunoscintigraphic study with anti-CEA monoclonal antibody (DG2). AB - Monoclonal antibody D11-DG2 (DG2) against carcinoembryonic antigen (CEA) was examined for suitability for radioimmunodetection of human tumors grown in nude mice. Antibodies DG2 and a control antibody of the same IgG1 subclass were labeled with 131I and injected into mice bearing one of three types of CEA containing tumors (cell lines LS 174T, HT-29 and Rec S) and/or a CEA-negative tumor (Rec R). Gamma-camera imaging and distribution studies revealed that CEA containing tumors selectively accumulate DG2 but Rec R does not. As the tumors differ in CEA-content, the highest accumulation of 131I-DG2 (corresponding to the best scintigraphic imaging) was found in LS 174T tumors, intermediate in Rec S and lowest in HT-29 tumors. The mean tumor-to-blood ratios on the sixth day after antibody administration were 4.6, 3.2, and 2.1, respectively, in the control experiments the value of this parameter was always lower than 1. The results showed the applicability of DG2 for immunoscintigraphic studies in patients. Furthermore, a positive correlation was found between the uptake of anti-CEA antibody and CEA-content in the tumors. PMID- 2320178 TI - Modulation of in vitro chemosensitivity by extracellular Ca++ in adriamycin sensitive and resistant P388 leukemic cells. AB - P388 mouse lymphocytic leukemia cells sensitive (P388/S) and resistant to adriamycin (P388/Adr), respectively, were exposed in vitro to 3 dose concentrations of adriamycin, mitoxantrone, vincristine and cisplatin in the presence and absence of extracellular Ca++ at 37 degrees C for 1 h. The absence of extracellular Ca++ enhanced the cytotoxicity of all the four drugs by 25 to 30% in P388/S cells. P388/Adr cells retained their resistance to adriamycin irrespective of the presence or absence of Ca++, however, vincristine and cisplatin to which P388/Adr cells, in normal course, show cross-resistance, exhibited a 30-40% enhancement of cytotoxicity in the absence of extracellular Ca++. Cross-resistance of P388/Adr to mitoxantrone was totally circumvented in the absence of extracellular Ca++. PMID- 2320179 TI - Action of retinoids during transformation of 10T1/2 cells. AB - The effect of three retinoids, 13-cis-retinoic acid, arotinoid ethyl sulfone and retinal acetate, on methylcholanthrene (MCA) induced transformation of 10T1/2 cells was studied. It appears that 13-cis-retinoic acid and arotinoid ethyl sulfone prevent transformation in a direct way at the last stage of carcinogenesis. Retinal acetate, however, requires cell-to-cell contacts to inhibit the transformation of 10T1/2 cells. PMID- 2320180 TI - Influence of "nuclear" estrogen receptor content on prognosis of early stage carcinoma of the uterine body. A short-time follow-up. AB - Sixty-five patients with Stage I and II endometrial carcinoma were investigated. After a short-time follow-up (17-24 months) significant differences in frequency of relapses were observed between patients with tumors containing low amounts of estrogen receptor (ER less than 60 fmol/mg DNA) in the nuclear pellet, and those with tumors containing greater than 60 fmol ER/mg DNA (p = 0.01). Other prognostic factors showed no differences in frequency of relapses. In this small patient material with a short-time follow-up we therefore suggest that ER in the nuclear pellet may be an important prognostic factor. PMID- 2320181 TI - Increased cathepsin B activity in human lung tumors. AB - The occurrence and levels of cathepsin B activity were investigated in primary human lung tumors and lung metastases of renal, colorectal and urinary bladder carcinomas as well as in the associated apparently normal lung parenchyma using a continuous rate enzyme assay with Ac-Leu-Arg-Arg-NHMec (7-(N-acetyl-L-leucyl-L arginyl-L-arginylamido)-4-methylcoumarin) as the fluorogenic substrate. The inhibition studies of the enzymic hydrolysis of the substrate provided evidence for the catalytic action of the cysteine proteinase cathepsin B (CB) in the lung tumor tissues and the lung parenchyma under the assay conditions used. In the studied group of twenty-four patients with primary lung tumors of all major histological types, the level of CB activity in the tumor tissue was increased twofold and more over that in the associated lung parenchyma in 83% and 75% of cases, when expressed on the basis of wet tissue weight and tissue DNA, respectively. In patients with primary lung adenocarcinoma, the activity of the enzyme in the tumor tissue was elevated over that in the lung parenchyma in all cases studied. In both subgroups of patients with squamous cell lung carcinoma and adenocarcinoma, the mean cathepsin B activity was significantly higher in the tumor tissue than in the lung parenchyma. No obvious correlation was found between the tissue level of cathepsin B activity and the stage of primary lung tumor disease. In a limited number of patients with lung metastases, the level of cathepsin B activity was also higher in the tumor tissue than in the lung parenchyma. PMID- 2320182 TI - IgG1-4 subclasses in paraproteinemias. AB - The concentration of IgG1-4 subclasses was determined in a series of 10 IgG1 paraproteinemias (5 multiple myelomas and 5 non-myeloma paraproteinemias) and in a series of 11 IgA paraproteinemias (7 multiple myelomas and 4 non-myeloma paraproteinemias). In the group of IgG1 myelomas, deficiency was established in the subclasses IgG2-4, in the group of IgA myelomas, deficiency was proved in all IgG1-4 subclasses as compared with non-myeloma paraproteinemias. Decreased IgG heterogeneity in IgG1 myelomas was demonstrated by the method of isoelectric focusing. PMID- 2320183 TI - A new chemotherapeutic regimen in the treatment of advanced gastric cancer. AB - The results of different chemotherapeutic regimens used in the treatment of advanced gastric cancer are compared. Three groups of patients were evaluated. The first group (59 patients) was treated by a new regimen consisting of methotrexate, 5-fluorouracil, cyclophosphamide and lederfolin (MFC + CF), the second group (21 patients) was treated by COnFU regimen (cyclophosphamide, vincristine, 5-fluorouracil), and the third group (35 patients) was treated with 5-fluorouracil (5-FU) alone. The control group of 41 patients with advanced gastric cancer was not treated cytostatically. The percentages of positive responses were as follows: 49.2% in the group treated with the new regimen, 33.3% in the COnFU group, and 14.3% in the 5-fluorouracil group. Median survival time of patients treated with the new regimen was significantly longer than that in the control group. Toxicity resulting from the new regimen treatment was moderate. The results of the new regimen can be compared to those obtained by other authors using the FAM regimen. PMID- 2320184 TI - The results of Vepesid therapy in the treatment of malignant lymphomas. AB - Twenty-three patients with Hodgkin's disease and non-Hodgkin's lymphomas were treated by Vepesid. The dose of the drug was 150 mg/m2 daily for 5 consecutive days. This schedule was repeated every 3 weeks. The percentage and response were estimated according to WHO scale. There were complete responses and 6 partial responses lasting 13.7 and 5 months, respectively, on the average. The results of Vepesid therapy depended on the efficiency of previous treatment. PMID- 2320185 TI - Radiation associated eosinophilia and monocytosis in carcinoma of the uterine cervix: a simple reliable clinical and prognostic indicator. AB - Clinical and prognostic significance of radiation associated eosinophilia (RAE) and radiation associated monocytosis (RAM) was evaluated in 176 patients with squamous cell carcinoma of the uterine cervix followed up after radiotherapy. Significant RAE was noticed in patients with Stages I/IIA and IIB who remained disease-free after treatment. On the contrary, patients belonging to these two stages but who developed recurrent disease showed absence of RAE. These patients as well as those belonging to Stage III showed considerably higher levels of RAM as compared to those patients remaining disease-free. These observations showed the usefulness of these two simple inexpensively carried out parameters in prognosticating disease course in malignant cervical neoplasia. PMID- 2320186 TI - Comparative study of breast cancer risk factors in Estonia and Slovakia. East European Study Group of Breast Cancer Epidemiology. AB - Selected more or less known risk factors of breast cancer were investigated and compared in this case-control study in Estonian and Slovak women. The results revealed that women who gave birth to the first child before the age of 20 years had one-fifth and one-third breast cancer risk in Estonia and Slovakia, respectively, in relation to nulliparous women. Concerning subsequent births, Estonian women with two children showed the lowest relative risk, while in Slovak women this risk decreased with increasing parity. Only in women from Slovakia who gave the first birth at, and after the age of 30 years, significantly elevated breast cancer risk was observed. In this study there was no evidence of an association between breast cancer risk and the age at menarche, although an increasing trend of the variable early menarche was apparent in both female populations studied. In addition, an increase in the risk was revealed among obese Estonian women, and thyroid diseases were found to be related with a twofold excess of breast cancer risk in Slovak women. The possible existence of differences in risk factors in the populations showing similar breast cancer incidence rates is discussed. PMID- 2320187 TI - [The "immunologic profile" of amyotrophic lateral sclerosis]. PMID- 2320188 TI - [Isolated sarcoidosis of the central nervous system. A case report]. PMID- 2320189 TI - [Diffuse primary non-Hodgkin's lymphoma of the central nervous system]. PMID- 2320190 TI - [A case of simultaneous occurrence of myasthenia gravis and multiple sclerosis]. PMID- 2320191 TI - [Bilateral thalamic lesions in cerebral venous thrombosis]. PMID- 2320192 TI - [Restless legs syndrome. Clinical aspects, differential diagnosis, therapeutic approaches]. PMID- 2320193 TI - [Adrenoleukodystrophy: the significance of peroxisomal disease in adult neurology]. PMID- 2320194 TI - [Clinical and pathologic-anatomic findings in acute basilar thromboses. A study of 30 autopsy verified cases]. AB - In a retrospective study of 30 cases with fatal basilar artery thrombosis we compared clinical and autopsy findings for clinicopathological correlation. There are only few clinical symptoms which point to a definite localisation and extent of thrombosis or cerebral infarction. In most cases loss of consciousness and hemi- or tetraparesis are due to pontine or mesencephalic infarction. Palsy of the facial nerve suggests infarction of the pons. The incidence of cranial nerve involvement is too low to allow localisation of infarction. There was no case showing infarction of the diencephalon or the medulla oblongata when pontine or mesencephalic structures were intact. Moreover, these infarctions remained clinically silent. No clinical predictors of outcome could be defined. Even in patients without detectable impairment of consciousness or stenosis of the vertebral arteries, the disease may prove fatal. PMID- 2320195 TI - [Comparative psychological test studies of the intellectual ability of Parkinson patients]. AB - Patients with Parkinson's disease (n = 81) are compared with normal controls and three clinical groups, each representing a different level of cerebral impairment (TIA; Stroke; Alzheimer's disease (AD) and multi-infarct dementia (MID). Psychometric measures of abstract reasoning, speed of information processing, verbal and visual memory, visuospatial perception and psychomotor functions are taken using a neuropsychological test battery with appropriate age-correction and normalized scaling. Following differentiation between the uncomplicated idiopathic Parkinson's syndrome and Parkinson plus (signs of cerebral polypathy and/or a degenerative process exceeding the nigro-striatal system) the neuropsychological profile reveals intellectual impairments approaching the dementia level (AD/MID) only in the Parkinson plus subgroup. With the exception of the severe motor deficiencies, the overall performance of patients with an uncomplicated Parkinson's syndrome is largely on the level of age-matched controls. Slight deficits exist only in the speed of information processing (action under time restriction) and in visuoconstructive performance. PMID- 2320196 TI - [The effect of acetazolamide-induced, endogenous volume stress of the cerebrospinal system on intracranial pressure. Diamox--effect on intracranial pressure]. AB - In 16 patients with possible disturbed CSF circulation longterm recording of intracranial pressure (ICP) was performed. In 9 of the 16 patients the disorder became evident after the application of an exogenous volume-pressure testing procedure. This procedure enabled a classification into a group I--disturbed CSF circulation (8 patients)--and another group II--normal CSF circulation (8 patients). During a routine Xenon-CT-CBF study all patients of both groups were given to 1 g acetazolamide (DIAMOX) intravenously. Before, during and after the administration of DIAMOX the epidural ICP was continuously measured. An increase in ICP was monitored in all patients. In group I the average initial ICP was 13.6 +/- 7.6 mmHg. The maximum ICP was reached within a time interval of 13.1 +/- 4.5 min after DIAMOX administration. At this time the mean ICP was 36.4 +/- 19.2 mmHg (p less than 0.01). The average initial ICP in group II was 6.3 +/- 4.2 mmHg. The maximum ICP was reached within a time interval of 13.6 +/- 1.1 min. At this time the mean ICP was 11.9 +/- 4.8 mmHg (p less than 0.01). In respect to the maximum ICP both groups were significantly different (p less than 0.01). Despite a considerably rising ICP up to values of about 50 to 70 mmHg in several patients of group I only 1 patient complained of being sick. Presumingly, an ICP elevation caused by vasodilatation would be better tolerated than ICP elevations due to other causes. PMID- 2320197 TI - [Cerebral perfusion pressure in acute blood pressure decrease with hyperosmolar sorbitol in anesthesia conditions]. AB - Osmotherapy with sorbitol during intracranial surgery caused a significant decrease in arterial blood pressure. It was shown that this sometimes very desirable reaction did not cause relevant decreases in cerebral perfusion pressure, but was on the contrary accompanied by an increase in cerebral perfusion pressure in patients with severely elevated ICP (greater than 30 mmHg). 8 patients were studied by measuring the arterial and intracranial pressure during intraoperative infusions of sorbitol 40% (3 ml/kg body weight). Our findings are explained by the simultaneous decrease in arterial and intracranial pressure. During intracranial surgery sorbitol can be used as the antihypertensive agent of choice for treating hypertensive dysregulation of arterial blood pressure in the initial phase of craniotomy before opening the dura. PMID- 2320198 TI - [Cerebrospinal fluid dynamics in experimental subarachnoid hemorrhage]. AB - To investigate the acute effects on intracerebral pressure, intracranial reserve capacity and CSF absorption resistance, a subarachnoidal haemorrhage was induced experimentally in a cat by bolus injection or continuous infusion of autologous blood into the cisterna magna. Intracisternal bolus injection resulted in a brief steep increase in intracranial pressure. 30 or 60 minutes after the haemorrhage the median intracranial pressure is slightly increased, the reserve capacity markedly reduced and the CSF absorption resistance considerably enhanced. During intracisternal blood infusion there is a continuous intracerebral pressure rise that persists to the end of the infusion and decrease again within a short time. This intracranial pressure behaviour is due to the simultaneous reduction of intracranial reserve capacity and the increase in CSF absorption resistance during the blood infusion. PMID- 2320199 TI - [Results of intervertebral disk surgery in advanced age]. AB - Among 2983 patients operated upon for herniated lumbar disks from 1981 through 1985 193 were between 65 and 84 years of age. Many of them had long-standing histories of recurrent sciatica. Most patients presented with unilateral or bilateral radicular pain, motor weakness or paresis and typical sensory changes. The usual type of conservative treatment had been tried in all patients before operation was recommended. Although our patients were, due to their advanced age and medical problems less than optimal surgical risks, we did not encounter a single perioperative mortality and postoperative complications were limited. The mean duration of hospitalisation was 15.1 days. Surgical results were quite encouraging, since 80.3% of the patients reported satisfactory resolution of their preoperative pain, motor weakness and sensory changes. Since most patients can achieve relief of their preoperative pain, it is not justified to restrict operative treatment only because of advanced age despite a number of preoperative risk factors. PMID- 2320200 TI - [Spinal fusions in rheumatic dislocation of the cranio-cervical transition]. AB - In 37 patients suffering from rheumatoid arthritis fusions of the cranio-cervical region were performed. The different techniques of fusions are reported and their complications and rate of pseudoarthrosis are mentioned. In detail a modified technique of transarticular screwing according to the method of Magerl are given. PMID- 2320201 TI - [Classification of trigeminal neuralgia and its effect on the results of surgical treatment]. AB - The trigeminal neuralgia has to be differentiated from the trigeminal neuropathy in respect of pain character and etiology. The neuralgia is characterized by paroxysmal pain evoked by trigger stimuli. The most frequent cause of this type of pain is a parapontine vascular compression of the trigeminal root without neurological deficits. The symptoms of neuropathy are some sensory loss associated with continuous pain resulting from peripheral damage of the trigeminal nerve. This distinction alleviates the indication for specific operative procedures and is more precise than the subdivision in typical and atypical neuralgia. The results of neurovascular decompression and thermorhizotomy can be much improved if neuropathic pain syndromes are excluded from operation. Out of 180 patients suffering from trigeminal neuralgia 94% were pain-free after neurovascular decompression and 96% of 144 patients following thermorhizotomy. For the treatment of continuous neuropathic pain augmentative electrostimulation of the Gasserian Ganglion via implanted electrodes is recommended. PMID- 2320202 TI - Kinetics and glial fibrillary acidic (GFA) protein production in a transplantable human giant cell glioblastoma (D-212 MG) of near haploid karyotype maintained in an organ culture system. An immunohistochemistry study. AB - A transplantable subcutaneous tumour (designated D-212 MG), sequentially passaged in athymic nude mice and originally derived from a human giant cell glioblastoma, was maintained in an organ culture (matrix) system and studied immunohistochemically after in vitro pulse-labelling with bromodeoxyuridine (BrdU) and for the presence of glial fibrillary acidic (GFA) protein, after 1, 2 and 3 weeks in culture. The histological characteristics of the tumour, showing two cell populations of giant multinucleated cells and small cells, were preserved in the explants. An increased percentage of multinucleated giant cells was found after 3 weeks in vitro. A small but constant fraction (4-6%) of these cells continued to synthesize DNA. The labelling index of the small cells was somewhat higher, but decreased slightly although significantly over the 3-week period in vitro (from approximately 10.5 to 8%). The percentage of small cells that were positive for GFA protein was in the region of 75% and that of the giant multinucleated cells was in the region of 45%; it did not change significantly during the 3 weeks in vitro. The in vitro results confirm the astrocytic nature of both the small cells and the giant multinucleated cells in this tumour, the capacity of both cell populations to synthesize DNA in culture and to demonstrate invasiveness, and suggest the possibility that some of the giant multinucleated cells may have originated from the conversion of a number of small tumour cells. PMID- 2320203 TI - Repair of the ependyma in hydrocephalic brains. AB - Hydrocephalus was induced in 12-day-old rats by the cisternal infusion of concentrated kaolin suspension. At 19 days of age, a lesion, 100 or 150 microns in diameter, was made in the ependymal lining of the lateral ventricles. Animals were killed at intervals from 1 h to 20 days after the lesion was made. The damaged area was examined by scanning electron microscopy, light and transmission electron microscopy. Between 1 h and 48 h the hole was still open. Small round cells, identified as free subependymal cells, were associated with the edges of the hole from 1 h after the lesion was made. From 48 h, the lesion was completely covered with cell bodies and their processes and no hole was present. Signs of differentiation were seen in the free subependymal cells from 4 days, the cells becoming more electron lucent. By 15 days, three types of cell arrangement were seen within the damaged area: 1 clusters of small cells, with few processes, resembling subependymal cells; 2 small numbers of cells with flat cytoplasmic processes which formed the lining of the ventricular wall; 3 clusters of cells with long thin processes attached to the surface of the ventricular wall but not forming the ependymal lining. The results of this study suggest that, in the hydrocephalic brain, ependymal damage and the repair of a defect within the ventricular wall is initiated by subependymal cells. PMID- 2320204 TI - Regeneration of nerve fibres in the anterior medullary velum of neonatal and weanling rats. AB - The responses to injury of myelinated central axons in neonatal (5-day) and weanling (30-day) rats were compared, using the trochlear nerve fibres in the anterior medullary velum (AMV) as an experimental system. In intact animals, fibres of the trochlear nerve decussate completely in the AMV, to enter the contralateral nerve. Sprouting from proximal axon stumps was seen within 36 h after injury in silver-stained, whole mounts of mid-sagittally lesioned AMVs from weanlings. Subsequent growth produced a tangled axon mass which persisted until 15-20 days post-lesion (d.p.l.) but then began to degenerate. By 50 d.p.l., the majority of surviving axons looped within the AMV to enter the ipsilateral trochlear nerve; few axons remained growing randomly within the AMV. Axonal debris persisted within the velum 50 d.p.l. In neonatal rats, lesioned trochlear axons initially developed axon sprouts, but then degenerated with rapid clearance of debris, leaving the AMV devoid of both axons and degeneration products by 6 d.p.l. From 8 d.p.l., the velum became repopulated by axons which either grew randomly or looped to enter the ipsilateral peripheral nerve. Both patterns of axon growth were still observed 50 d.p.l. In both experimental groups, horseradish peroxidase injection to the right superior oblique muscle 40 d.p.l. indicated that at least some of the looping fibres observed within the lesioned AMVs originated in the ipsilateral trochlear nucleus. The origin of those axons growing randomly within the AMVs of neonatally-lesioned animals is unknown. The results are discussed with reference to current ideas concerning regeneration inhibiting elements in the CNS, and regeneration-promoting factors in the PNS. PMID- 2320205 TI - Interstitial brachytherapy for malignant brain tumors: preliminary results. AB - The authors report their experience with interstitial brachytherapy in 46 patients with malignant brain tumors. Twenty-three patients received implants after external radiation for newly diagnosed malignant astrocytoma, as part of a randomized study (Group I). Eighteen patients received implants for recurrent malignant astrocytoma (Group II) and 3 for recurrent solitary cerebral metastasis from adenocarcinoma of the lung (Group III). Two additional patients received implants as part of their initial therapy for a radiation-induced malignant astrocytoma and a malignant fibrous histiocytoma. In all patients high-activity iodine-125 sources were implanted temporarily by a stereotactic technique. To date 50 patients have been entered in the randomized study with a maximum follow up of 31 months. The small numbers and short follow-up preclude any conclusions regarding the efficacy of brachytherapy used as part of initial therapy. The median survival to date in the 23 patients in this group who received implants is 60 weeks. The median survival to date for the 18 patients who received implants for recurrent malignant astrocytoma is 44 weeks postimplant. Two of the three patients who received implants for recurrent solitary metastasis are alive at 41 and 49 weeks postimplant; a third died at 39 weeks postimplant. Significant complications attributable to interstitial brachytherapy have been observed in 10 of 46 patients (21.7%). A second operation for clinical and radiological deterioration was performed in 12 patients (26.1%) 8 to 105 weeks after brachytherapy. The authors conclude that interstitial brachytherapy is beneficial for selected patients with recurrent malignant astrocytoma and solitary recurrent metastasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2320206 TI - Tumor localization of human brain malignant glioma xenograft in nude mice with a radiolabeled monoclonal antibody. AB - A murine monoclonal antibody designated as MAb 3H9 (IgG1 subclass immunoglobulin, kappa light chain) expressed specific antibody binding activity to a human brain malignant glioma cell line (GBM8401/TSGH,NDMC) and many formalin-fixed and paraffin-embedded malignant gliomas that have been produced in our laboratory by hybridoma technology. The immunohistochemical indirect immunofluorescence, peroxidase-antiperoxidase assays, and specific electron microscopic immunogold staining revealed that 3H9 probably recognized a distinct glioma-associated surface antigen on the GBM8401 cultured cells. In vivo radioimmunolocalization of GBM8401 xenografts in nude mice by external scintigraphy with radiolabeled 3H9 has been performed to evaluate potential clinical application as diagnostic or therapeutic reagents. On the 3rd day after an intravenous injection of 15 microCi, the 125I- or 131I-radiolabeled 3H9 was successful in immunolocalization of a human brain GBM8401 xenograft in the nude mouse. In large xenografts, the radioactivity ratios of tumor to brain and tumor to blood were 11.0 and 2.4, respectively. In small xenografts, the tumor to brain and tumor to blood ratios were 14.0 and 2.9, respectively. The clearance of radiolabeled 3H9 in the bloodstream of the nude mouse was not affected by the presence of a GBM8401 xenograft. This preliminary experiment reveals that human brain GBM8401 xenografts in nude mice can be detected in vivo by radiolabeled 3H9. PMID- 2320207 TI - Anticopper treatment inhibits pseudopodial protrusion and the invasive spread of 9L gliosarcoma cells in the rat brain. AB - The copper ion, a cofactor of angiogenesis, is sequestered in human brain tumors and the adjacent brain. The invasive spread of neoplastic cells has been linked to angiogenesis and involves similar mechanisms of migration and tumor-matrix interaction. In this report, copper depletion inhibited the infiltrative spread of the normally invasive 9L gliosarcoma. Twenty made Fischer 344 rats were each injected with 1 X 10(5) 9L cells; 10 rats were treated with a low-copper diet and penicillamine. In the normocupremic control rats, a "diffuse" invasive pattern was observed in all 10 animals. In the hypocupremic group, a "nodular" pattern, with a discrete border between tumor and brain, was found in 7 of 10 rats (P less than 0.01). In a second experiment, the brains of 16 tumor-bearing rats were studied by electron microscopy. In the 8 normocupremic control rats, cytoplasmic extensions and pseudopodial protrusions, cytological markers of invasive cells, were prominent at the tumor-brain interface. In striking contrast, pseudopodia were absent along the border of the tumors in the 8 hypocupremic rats. These findings suggest a biological role of copper in the neoplastic spread of brain tumor cells. Pharmacological and metabolic alteration of the cellular microenvironment to inhibit invasiveness represents a novel therapeutic approach, especially for tumors of the brain in which malignancy is a function of regional invasiveness. PMID- 2320208 TI - Long-term intraventricular infusion of morphine for intractable pain in cancer of the head and neck. AB - The authors' experience with seven patients with intractable pain that was treated by continuous intraventricular infusion of morphine through an implanted Infusaid pump is reported. The pain was caused by head and neck cancer in six patients and was associated with postpolio syndrome in one. The average follow-up was 7 months. Pain was effectively managed through intraventricular administration of a combination of morphine and mild oral narcotic analgesics. Complications included one case of transient respiratory depression, one pump pocket infection, and one pump failure. The morphine dose required to maintain analgesia increased over time in all patients treated. This is a safe and effective method of pain management in patients with head and neck cancer. It is useful as well in patients who have intractable pain that cannot be managed through an intrathecal route because of a contraindication to lumbar puncture or an inaccessible subarachnoid space. PMID- 2320209 TI - Pericyte degeneration and thickening of basement membranes of cerebral microvessels in complex partial seizures: electron microscopic study of surgically removed tissue. AB - Complex partial seizures are associated with alterations in regional cerebral blood flow in abnormally spiking foci, as shown by positron emission tomography and single photon emission computed tomography, with an increase in flow ictally and a decrease interictally. Alterations of vasoregulation during ictal periods have also been described in animal seizure models. An electron microscopic study on human brain tissue from seven patients undergoing resections for the treatment of intractable complex partial seizures was performed to examine ultrastructural changes of the microvasculature and their locations within the microvessel wall. Biopsies were obtained intraoperatively from temporal lobe regions with electrocorticographically detected abnormal spiking and from regions without abnormality on electrocorticograms (control samples) removed as part of the therapeutic resection. A total of 539 microvessels from three regions were evaluated: spiking mesial temporal lobe, spiking lateral temporal cortex, and nonspiking (control) cortex. Evidence of pericyte degeneration (aggregates of cellular debris within the basement membrane) was noted in the majority of spiking area microvessels (76.7% in spiking mesial temporal cortex; 69.8% in spiking lateral temporal cortex) as compared with 37.8% of control microvessels (P less than 0.0005). Morphometric studies revealed a significant increase in total wall thickness, pericyte-basement membrane unit thickness, pericyte cytoplasmic density, basement membrane density, and basement membrane thickness in microvessels from spiking (mesial and lateral temporal cortex), as compared to control areas (P less than 0.01). No statistically significant difference was noted in pericyte coverage or pericyte or endothelial mitochondrial densities between microvessels in spiking and control regions. This study shows degeneration of pericytes, cells thought to play an essential role in microvascular hemodynamics, and thickening of microvessel walls in abnormally spiking brain regions in patients with intractable complex partial seizures. The pericyte degeneration and basement membrane thickening in abnormally spiking areas may explain alterations in vasoregulation, by a decrease in the microvascular compliance and in cross-capillary diffusion. PMID- 2320210 TI - A clinical evaluation of the Camino subdural screw and ventricular monitoring kits. AB - The aim of this study was to compare readings of intracranial pressure from a ventricular catheter with those obtained from a Camino catheter-tipped transducer. The Camino transducer was evaluated in two ways: firstly, when it was inserted by a subdural screw, and secondly, when it was inserted into a ventricular catheter using a ventricular monitoring kit. Data were recorded for 376 hours for the subdural screw method and for 486 hours for the ventricular monitoring kit. Average pressure readings were calculated every 5 minutes (10 half-minute values), and regression analysis was performed. For the subdural screw method, the correlation coefficient was 0.945 (gradient, 1.04; intercept, 5.51. The results from the ventricular monitoring kit showed that the correlation coefficient was 0.901 (gradient, 0.93; intercept, -0.92. The correlation between recordings of ventricular fluid pressure and the Camino recordings obtained from both subdural screw insertions and ventricular monitoring kits was good, with the subdural screw method proving more accurate and reliable in clinical use. PMID- 2320211 TI - Quantification of changes in serotonin uptake with spinal cord injury. AB - The high-affinity uptake of [3H]serotonin was studied using spinal cord preparations obtained from normal dogs, dogs made paraplegic by midthoracic transection, and dogs made monoplegic by midthoracic hemisection. Measurements were made at 1, 4, and 8 weeks after surgery. Lumbar spinal cord was removed at the above time periods and a myelin-free synaptosomal fraction was obtained by centrifugation and used for studying high-affinity serotonin uptake. At 1 week, there were no significant differences for Km values (nM) among any of the three groups (138 +/- 20, 128 +/- 22, and 118 +/- 20). The Vmax values (pmol/min/mg of protein) at 1 week for the control group (4.9 +/- 0.6) versus the hemisected group (4.3 +/- 0.7) were not significantly different. The Vmax values at 1 week for the completely transected group (2.3 +/- 0.3; P less than 0.01) were significantly reduced by 53 +/- 7%. At 4 weeks, the Vmax values for the hemisected (1.8 +/- 0.2; P less than 0.05) and transected groups (0.6 +/- 0.2; P less than 0.05) were significantly different as compared to the control group. The mean percent drop in Vmax after hemisection was 56 +/- 4%, close to the predicted value of 50%. The mean percent drop in Vmax after transection was 86 +/ 2%. At 8 weeks the mean Vmax values for the hemisected (1.9 +/- 0.3; P less than 0.05) and transected (0.4 +/- 0.4; P less than 0.05) groups were not significantly different compared to their respective 4-week values. It appears that serotonin uptake can be used to quantitate roughly the degree of spinal cord injury. PMID- 2320212 TI - The diagnosis and treatment of pediatric lumbar spine injuries caused by rear seat lap belts. AB - Over the past 3 years, during a time when seat belt use has increased, we have managed nine midlumbar spine fractures in children caused by standard rear seat lap belts. Children with a lap belt injury typically complained of abdominal and back pain, and the nature of their injuries was evident by the presence of a belt shaped abrasion across the lower abdomen. Midlumbar spine fracture may be associated with paraplegia and life-threatening visceral injury. If the spine is analyzed as a beam, the full spectrum of the reported injuries is predictable. This study shows that the rear seat belts installed as standard equipment do not meet the special needs of children. Rear seat lap belts are better than no restraints, but the addition of a shoulder restraint is strongly advocated to reduce lumbar spine injury. PMID- 2320213 TI - Delayed and progressive multiple suture craniosynostosis. AB - A considerable amount of information is available on various types of craniosynostoses. The patient exhibiting single suture synostosis that progresses to involve multiple sutures is distinctly uncommon, as is the patient exhibiting delayed synostosis involving all of the calvarial sutures. We report a group of 11 such patients with progressive and delayed holocalvarial synostosis. Most patients exhibited features of raised intracranial pressure or developmental delay, and in all patients symptoms were relieved after surgery. The diagnostic and therapeutic implications of this type of presentation in craniosynostosis are discussed. PMID- 2320214 TI - Surgical removal of pontomesencephalic cavernous hemangiomas. AB - Cavernous hemangiomas of the brain stem are usually discovered accidentally during evacuation of a hematoma, and successful surgical treatment of these lesions is seldom achieved. With the increasing use of magnetic resonance imaging, the presence of a cavernous hemangioma can be detected before surgery, allowing an elective surgical approach. We successfully removed pontomesencephalic cavernous hemangiomas from 2 patients and pontomedullary hemangiomas from 2 others. Elective surgery was performed with perioperative bimodal monitoring of somatosensory and auditory evoked potentials. Performing surgery soon after the hemorrhage minimizes the risk of additional postoperative neurological deficit, since surgical excision is facilitated when the hematoma is not completely organized. Pontine hemangiomas are approached via the 4th ventricle. Mesencephalic hemangiomas are removed by a midline supracerebellar approach when they are lateralized by using a subtemporal approach. The lesion can be removed through a small incision in the brain stem at the site of the lesion. The favorable results, which include marked improvement of preoperative neurological deficits and documentation of complete removal of the lesion by magnetic resonance imaging, support a more aggressive approach to the treatment of symptomatic cavernous hemangiomas of the brain stem. Further investigation of the natural history of these lesions is mandatory. PMID- 2320215 TI - Intracranial vertebral endarterectomy. AB - Intracranial vertebral endarterectomy was performed on six patients with vertebrobasilar insufficiency in whom medical therapy failed. The patients underwent operations for stenotic plaque in the intracranial vertebral artery with the opposite vertebral artery being occluded, hypoplastic, or severely stenosed. In four of the patients, the stenosis was mainly proximal to the posterior inferior cerebellar artery (PICA). In this group, after endarterectomy, the vertebral artery was patent in two patients, and their symptoms resolved; in one patient the endarterectomy occluded, but the patient's symptoms improved; and in one patient the endarterectomy was unsuccessful, and he continued to have symptoms. In one patient, the plaque was at the origin of the PICA. The operation appeared technically to be successful, but the patient developed a cerebellar infarction and died. In one patient the stenosis was distal to the PICA. During endarterectomy, the plaque was found to invade the posterior wall of the vertebral artery. The vertebral artery was ligated, and the patient developed a Wallenburg syndrome. The results of superficial temporal artery to superior cerebellar artery anastomosis are better than those for intracranial vertebral endarterectomy for patients with symptomatic intracranial vertebral artery stenosis. The use of intracranial vertebral endarterectomy should be limited to patients who have disabling symptoms despite medical therapy, a focal lesion proximal to the PICA, and a patent posterior circulation collateral or bypass. PMID- 2320216 TI - The perforating branches of the internal carotid artery: the microsurgical anatomy of their extracerebral segments. AB - The perforating branches of the internal carotid artery (ICA) were examined in 30 forebrain hemispheres. These branches were present in all the cases studied, and varied from 1 to 6 in number (mean, 3.1). Their diameters ranged from 70 to 470 microns (mean, 243 microns). The perforating branches arose from the choroidal segment of the ICA, that is, from its caudal surface (52.3%), caudolateral surface (34.1%), or caudomedial surface (13.6%). They rarely originated from the bifurcation point of the ICA (10%). The distance of the remaining 90% of the perforators from the summit of the ICA measured between 0.6 and 4.6 mm. The perforating branches most often originated as individual vessels, and less frequently from a common stem with another vessel or by sharing the same origin site with another perforator or with the anterior choroidal artery. The bifurcation of the ICA, which is a frequent site for cerebral aneurysms, is surrounded by many perforating branches. Hence, great care must be taken to avoid damage to these important vessels during operations in that region. PMID- 2320217 TI - Local cerebral glucose metabolism after global ischemia: treatment by ventriculocisternal perfusion with a fluorocarbon emulsion. AB - The local cerebral metabolic rate for glucose (LCMRg) was measured in cats subjected to global cerebral ischemia (GCI). Control (nonperfused) cats showed decreased LCMRg (P less than 0.01) in the frontal, temporal, parietal, and occipital cortex 9.5 hours after a 10-minute exposure to GCI. Cats perfused ventriculocisternally with oxygenated nutrient solution (ONS) for 8 hours showed significant increases in the LCMRg (p less than 0.05) at 9.5 hours postischemia in the parietal and occipital areas over the levels found in untreated ischemic cats. Supplementing the ONS perfusion medium with fluorocarbon (OFNS) increased the LCMRg (P less than 0.05) in the frontal, as well as the parietal and occipital areas, over that seen in untreated ischemic brains. The increase of LCMRg in three (rather than only two) cortical areas may be a result of the ability of the fluorocarbon in OFNS to deliver greater quantities of oxygen to the brain than ONS without fluorocarbon. Perfusion with OFNS without glucose, or with low (50 mg%) glucose, was more effective than OFNS with high (200 mg%) glucose in restoring LCMRg to normal in all four cortical areas affected by GCI. In five brain areas not affected by GCI, perfusion with OFNS having no glucose significantly increased LCMRg as compared to normal animals. This study demonstrates that OFNS perfused by the ventriculocisternal route can restore toward normal the LCMRg following GCI and that different concentrations of glucose in the perfusing fluid will have variable effects on LCMRg in certain brain areas. PMID- 2320218 TI - Adrenal medulla transplantation into the putamen in Parkinson's disease. AB - Autologous adrenal medulla was transplanted into the putamen of a patient with severe Parkinson's disease. After the operation, the patient's akinesia and rigidity decreased and the duration of action of L-dopa treatment was prolonged. The effect lasted for only 6 months, however, following which the patient's condition gradually began to deteriorate again, returning to the preoperative state by 12 months after surgery. This paper discusses possible reasons why the effect was only temporary. PMID- 2320219 TI - Neuronal migration anomalies causing extensive ventricular indentation. AB - Neuronal migration disorders include various anomalies of the brain, and cortical heterotopia is the most common type. In this report, we present the radiological findings of two adults with unusually large cortical heterotopia associated with fused-lip schizencephaly that caused extensive ventricular indentation. The lesion showed density on a computed tomographic scan and signal intensity on a magnetic resonance imaging scan similar to normal gray matter. Perifocal edema, contrast enhancement, and calcification were not seen. An abnormally decreased volume of the ipsilateral cerebral hemisphere, the presence of adjacent microgyri, and deep fissures that contained blood vessels were also characteristic findings, indicating abnormal development. Knowledge of this entity is important in differentiating true intracerebral neoplasms. PMID- 2320220 TI - Median nerve injury from local steroid injection in carpal tunnel syndrome. AB - Local steroid injections for symptomatic relief of carpal tunnel syndrome have become common in the evaluation and treatment of this disorder; yet reports of median nerve injection injury from this practice are rare. We present a case of nerve injury from a steroid injection in a 24-year-old man with carpal tunnel syndrome that was successfully treated by division of the transverse carpal ligament and neurolysis. The histopathological characteristics of the lesion are presented, and the pathogenesis and treatment of this injury are discussed. Means of avoiding this complication include careful attention to anatomic landmarks as well as to the patient's subjective response during injection and avoidance of the use of local anesthetics. PMID- 2320221 TI - Cerebrospinal fluid fistula secondary to ecchordosis physaliphora. AB - A patient with a large ecchordosis physaliphora extending from the sphenoid sinus into the subarachnoid space of the prepontine cistern and resulting in a cerebrospinal fluid fistula is described. Ecchordoses are most commonly asymptomatic and found only incidently at autopsy. This case report adds to the scant literature on symptomatic ecchordoses. The previously reported cases of symptomatic ecchordoses and intradural chordomas are briefly reviewed. Differentiation of chordoma and symptomatic ecchordosis may be difficult; however, the intradural location and relatively benign behavior of the latter are useful points. A discussion concerning the remnants of the notochord which persist in the adult and their role in the genesis of chordoma and ecchordosis physaliphora is also provided. PMID- 2320222 TI - Small bowel obstruction secondary to incomplete removal of a ventriculoperitoneal shunt: case report. AB - Small bowel obstruction and partial enteral loss secondary to entrapment by an incompletely removed ventriculoperitoneal shunt is a previously unreported hazard. PMID- 2320223 TI - Multiple peripheral aneurysms of the posterior inferior cerebellar artery associated with a cerebellar arteriovenous malformation: case report. AB - The authors describe a rare case of multiple peripheral aneurysms of the posterior inferior cerebellar artery found in association with a midline cerebellar arteriovenous malformation. Successful trapping of the aneurysms and excision of the arteriovenous malformation was accomplished with an excellent clinical result. The literature concerning aneurysms of the posterior inferior cerebellar artery, cerebellar arteriovenous malformations, and combined intracranial vascular abnormalities is discussed. PMID- 2320224 TI - Resolution of a recurrent/residual bacterial aneurysm during antibiotic therapy. AB - Management of patients harboring infectious intracranial aneurysms remains controversial because of the technical problems associated with the obliteration of these lesions as well as their frequent regression during antibiotic therapy. A case of a ruptured bacterial aneurysm of the distal middle cerebral artery in which a segment of the artery was found to be inflamed and necrotic is presented. The ruptured portion of the sac was clipped, leaving a small tag of aneurysmal tissue. Five days later, this tag was found to have expanded into a second aneurysm. This second lesion resolved with antibiotic therapy. Because of the responsiveness of infected cerebral arteries to the appropriate antibiotics, a less than radical surgical tactic may be a successful alternative to excision of the diseased arterial segment followed by distal revascularization in treating these lesions. PMID- 2320225 TI - Cerebral venous and sagittal sinus thrombosis after transcallosal removal of a colloid cyst of the third ventricle: case report. AB - The authors report a case of cortical vein and sagittal sinus thrombosis after a transcallosal removal of a colloid cyst of the third ventricle. Thirty-six hours after the operation, the patient developed focal seizures; after progressive deterioration, he died on the sixth postoperative day. At the autopsy, a venous hemorrhagic infarct in the right frontoparietal area and fresh thrombus occluding the sagittal sinus and cortical veins were found. The mechanism of cortical vein and sinus thrombosis subsequent to this procedure is discussed, and suggestions are made to prevent this serious complication. PMID- 2320226 TI - Application of decision analysis to unruptured arteriovenous malformations. PMID- 2320227 TI - Effects of crystalloid and colloid infusions on intracranial pressure. PMID- 2320228 TI - Pontine hemorrhage and trigeminal nerve impairment. PMID- 2320229 TI - Autonomic function and human immunodeficiency virus infection. AB - We compared autonomic function in 26 patients infected by the human immunodeficiency virus (HIV) (18 AIDS and 8 ARC) to 22 controls. A significant decline in autonomic function was present across groups. Autonomic dysfunction correlated strongly with signs of HIV-associated nervous system disease. We observed significant differences across groups in tests of heart rate variation (expiratory-inspiratory ratio, maximum minus minimum heart rate difference, and mean square successive difference), the mean arterial blood pressure fall to tilting, and the blood pressure response to isometric exercise. A trend of declining autonomic function from controls to AIDS was present in the 30:15 ratio, the Valsalva ration, the systolic blood pressure fall to standing and tilt, and the cold pressor test. We did not observe any correlation between autonomic dysfunction and individual neurologic signs, prior therapeutic agents, and concurrent HIV-associated inflammatory or neoplastic processes. This study provides support for the presence of autonomic dysfunction in association with HIV infection. Autonomic dysfunction occurs more frequently and with greater severity in patients with AIDS; however, it may be present in the early stages of HIV infection and appears to progress during the illness. PMID- 2320230 TI - Serial study of gadolinium-DTPA MRI enhancement in multiple sclerosis. AB - We performed serial baseline and gadolinium (Gd)-DTPA-enhanced MRI in 4 patients with definite multiple sclerosis. Studies were performed every month for a total of 4 scans. We obtained short TR/short TE sequences at 10 and 60 minutes after Gd DTPA injection. All patients had multiple hyperintense lesions seen on baseline MRI with long TR/short and long TE. There was Gd-DTPA enhancement in new, enlarging, and preexisting lesions that were unchanged in size. The enhancing lesions were always seen on T2-weighted images. There was no difference in enhancement between the 10- and 60-minute studies. Six of 85 preexisting lesions enhanced whereas all new or enlarging lesions enhanced. Enhancement persisted in only 1/3 of the new or enlarging lesions, suggesting that MR enhancement is a transient phenomenon due to local temporary blood-brain barrier breakdown. Our data indicate that Gd-DTPA enhancement monitoring is more sensitive than unenhanced MRI for detecting disease activity in MS. PMID- 2320231 TI - Motor neuron disease and amyotrophic lateral sclerosis: relation of high CSF protein content to paraproteinemia and clinical syndromes. AB - From 1984 to 1988, 11 of 120 patients (9%) with motor neuron disease (MND) had paraproteins detected by serum immunofixation electrophoresis (IFE), compared with 4 (3%) by cellulose acetate gels: 1 patient had progressive spinal muscular atrophy, 5 patients had amyotrophic lateral sclerosis (ALS), and 5 patients had ALS with probable upper motor neuron signs. Four of 5 patients (80%) with cerebrospinal fluid (CSF) protein content above 75 mg/dl had paraproteins, as did 6 of 30 with values above 50 mg/dl. Four of 14 patients with cerebrospinal oligoclonal bands (OCB) also had paraproteins. Two patients with ALS, CSF protein content above 75 mg/dl, and paraproteinemia had lymphoma. We conclude the following about patients with MND: high CSF protein content (especially above 75 mg/dl) or CSF OCB makes paraproteinemia more likely; some of these patients may have lymphoma; there is an inordinately high occurrence of paraproteinemia in MND; and IFE on agarose is more sensitive than electrophoresis on cellulose acetate in detecting paraproteins. Syndromes of paraproteinemia and high CSF protein are not restricted to the lower motor neuron but qualify as "ALS" with coexisting upper motor neuron signs. PMID- 2320232 TI - Survival of patients with amyotrophic lateral sclerosis in 2 Danish counties. AB - We investigated the survival of patients with amyotrophic lateral sclerosis (ALS) in a follow-up study of all patients hospitalized with the disease in 2 Danish counties during the period 1974 to 1986. There were 186 patients, with a mean age at diagnosis of 64.3 years. The median survival time was 12 months from diagnosis, the 3-year survival rate was 12%, and the 5-year survival rate 4%. (The corresponding figures from onset were 23 months, 26%, and 7%). Old age and bulbar findings at onset were negative prognostic factors. For each clinical category, the annual death rate remained constant throughout the observation period, indicating the effects of a steadily progressing degenerative disorder. We found no evidence of the existence of a separate variety of ALS, associated with long survival. PMID- 2320233 TI - The intracarotid amobarbital procedure as a predictor of memory failure following unilateral temporal lobectomy. AB - We investigated the efficacy of the intracarotid amobarbital procedure to accurately predict post-temporal lobectomy anterograde amnesia. We presented items at 2 separate times during amobarbital assessment; both early and late item recall were decreased during the injection contralateral to seizure onset indicating sensitivity to bilateral temporal lobe dysfunction. Ten patients for whom follow-up neuropsychological assessment was available failed either the early or late item recognition portions of their amobarbital evaluation ipsilateral to seizure onset, but had hippocampus included in the temporal lobectomy by virtue of satisfactory performance on other tests of hippocampal function. None of these 10 patients displayed postoperative anterograde amnesia, although there was a reduction in material-specific memory in some patients. These results indicate that relying solely on amobarbital memory testing to assess the functional ability of the contralateral temporal lobe to sustain global memory prior to temporal lobectomy may needlessly exclude patients from a viable therapeutic option. PMID- 2320234 TI - Prognostic significance of ventricular blood in supratentorial hemorrhage: a volumetric study. AB - We reviewed CTs from 47 patients with 48 spontaneous, supratentorial brain hemorrhages to determine the effect of ventricular blood on outcome. We correlated volumetric analysis of the parenchymal (P) and ventricular (V) blood, as well as other clinical and CT features, with clinical outcome in a statistical analysis. Hemorrhages were located in putamen 20/48 (42%), thalamus 13/48 (27%), lobar 9/48 (19%), caudate 3/48 (6%), and miscellaneous locations 3/48 (6%). Outcome in putaminal hemorrhages was highly correlated with the total (P + V) and P blood volumes, whereas the V blood was less important. For thalamic hemorrhages, outcome correlated more highly with the V and P + V volumes than with the P portion. Outcome for all hemorrhages was significantly correlated, in descending order of importance, with the severity of the initial neurologic deficit, P + V blood, hydrocephalus, the number of ventricles containing blood, P, V, and blood in the 4th ventricle. In general patients with more than 20 cc of V blood did poorly. Although hydrocephalus was associated with poor outcome, ventricular drainage did not benefit 8 of 9 patients. PMID- 2320235 TI - Progressive aphasia in a patient with Pick's disease: a neuropsychological, radiologic, and anatomic study. AB - Although Pick's disease is generally considered as a dementia characterized by signs of frontal lobe dysfunction, it can present with selective language defects rather than with cognitive decline. In this study, we report prospective and serial clinical, neuropsychological, and neuroradiologic observations in a 59 year-old man whose prominent disturbance was in the retrieval and learning of names denoting concrete entities and actions. Postmortem study confirmed the diagnosis of Pick's disease and revealed that neuronal loss and gliosis were most prominent in left anterior temporal cortices. The findings are in keeping with evidence that the left anterior temporal cortices and interconnected hippocampal system are critically involved in the learning and retrieval of verbal lexical items. The evidence from this patient, along with similar evidence from the literature we reviewed, suggests that when patients present with a progressive aphasia characterized by anomia, Pick's disease should be considered as the probable diagnosis. PMID- 2320236 TI - Prevalence of clinically diagnosed Alzheimer's disease and other dementing disorders: a door-to-door survey in Appignano, Macerata Province, Italy. AB - The purpose of this study was to investigate the prevalence of dementia in an Italian population using a door-to-door 2-phase design. As part of a social and health survey, we administered the Hodkinson abbreviated mental test to all persons over age 59 residing in the Commune of Appignano on January 1, 1987 (N = 778). We then investigated all subjects scoring 7 or less on the cognitive test following a standardized diagnostic protocol. We found 48 patients affected by dementia, yielding a crude prevalence ratio (cases per 100 population over age 59) of 6.2; prevalence ratios were 2.6 for Alzheimer's disease, 2.2 for multi infarct dementia, 0.8 for mixed dementia, 0.4 for secondary dementia, and 0.3 for unspecified dementia. Age- and sex-specific prevalence ratios increased steeply with age and were consistently higher in women for Alzheimer's disease and in men for dementia of all types and multi-infarct dementia. Alzheimer's disease was slightly more frequent than multi-infarct dementia; however, the most common type of dementia varied across age groups. Most cases of Alzheimer's disease were sporadic and had a late age of onset. Comparison with other populations suggests that dementia of all types is as frequent in Appignano as elsewhere, and that Alzheimer's disease might be more frequent in rural than in urban populations. PMID- 2320237 TI - Bodily neglect and orientational biases in unilateral neglect syndrome and normal subjects. AB - Patients with neglect erred toward the right when attempting to locate the intercepts of their midsagittal planes with a horizontal line placed in front of them. When control subjects could not see their bodies, they also pointed to the right. While control subjects improved when they were able to see their bodies, neglect subjects did not. When the horizontal line was moved toward the right, both neglect and control subjects increased their rightward pointing errors. However, patients with neglect made greater errors than did controls. When the line was in far left hemispace, controls pointed accurately to their midsagittal planes. The neglect subjects, in contrast, erred toward the left. Our results suggest that patients with neglect from right hemisphere lesions are not only inattentive to their bodies, but are also distracted by extracorporeal stimuli, especially on the right. Our results also suggest that normal subjects have a propensity to orient to or be distracted by stimuli in right hemispace. PMID- 2320238 TI - Topography of scalp potentials preceding self-initiated saccades. AB - We studied 3 scalp potentials recorded prior to saccades in relation to visual targets (the presaccadic negativity [PSN], presaccadic positivity [PSP], and spike potential [SP]) in normal subjects performing self-initiated saccades in darkness. There was a prominent PSN beginning at -800 msec, maximal at the vertex. This finding is consistent with activation of the supplementary eye field in the anterior mesial frontal cortex, a concept which correlates with cortical neuron recordings in monkeys and cerebral blood flow studies in humans. A widespread PSP, with greatest amplitude over the posterior scalp, suggests parieto-occipital participation even in the absence of visual targets. The sharp character of SP with focal lateralized frontal negativity, its "mirror image" scalp distribution when comparing leftward to rightward saccades, and its timing near the onset of saccades support an origin near the orbit, in either ocular motor nerves or muscles. PMID- 2320239 TI - Loss of P retinal ganglion cell function in resolved optic neuritis. AB - To determine the relative loss of P and M (X and Y) ganglion cell function in unilateral resolved optic neuritis, 10 patients with 20/20 or better Snellen acuity in both eyes had contrast sensitivity testing, color vision testing, and automated perimetry. We used contrast sensitivity gratings of 0.5 cycles per degree (cpd) with a rate of counterphase temporal modulation of 30 Hz and gratings of 11.4 cpd at 1 Hz. On 1 trial, patients responded when they detected the pattern of the grating and on the next trial when they 1st perceived movement. There was a significant difference in the 1 Hz high spatial frequency pattern and movement results suggesting loss of P cell function. Two patients were unable to perceive any movement with their involved eye with this target, but could detect the pattern. There was no significant difference between the involved and uninvolved eyes in the low spatial frequency pattern detection values. This is a function ascribed to the M cell. There was also loss of low spatial frequency movement detection. Although there was significant depression of the entire visual field in the involved eye, the probability plots showed the most significant loss in the cecocentral area. Farnsworth-Munsell 100 Hue color testing was also abnormal. Greater involvement of P than M ganglion cell axons may explain these contrast sensitivity abnormalities, central scotomata, and color vision loss. PMID- 2320240 TI - Reciprocal inhibition in cerebral palsy. AB - We studied reciprocal inhibition by recording the changes in firing probability of single motor units of the tibialis anterior muscle following stimulation of low-threshold afferents in the posterior tibial nerve. In 15 patients with cerebral palsy, the inhibition was as great or greater than normal. We found no evidence that group I afferents produce "reciprocal facilitation" in cerebral palsy. PMID- 2320241 TI - Diagonistic dyspraxia: case report and movement-related potentials. AB - We report unusual motor behavior of the left hand dissociated from conscious volition in a 51-year-old right-handed man. This patient had sustained damage to the anterior two-thirds of the corpus callosum, the rostral and lower parts of the right medial frontal lobe, and a small portion of the left medial frontal lobe. He subsequently showed 4 types of abnormal motor behavior in the left hand that were triggered by voluntary activities of the right hand: symmetric or antagonistic left hand movements; irrelevant movements of the left hand to the right hand; and a tendency to close the fingers of the left hand into a fist. Recordings of movement-related potentials revealed a marked attenuation of the Bereitschaftspotential (BP) over the right hemisphere observed only when the patient initiated voluntary activity with the right hand. Since the BP is believed to represent a cerebral cortical activity preparatory for voluntary movement, we infer that the level of dysfunction in this patient is at the motor preparatory level caused by a disconnection of the right hemisphere from the left. PMID- 2320242 TI - Ipsiversive eye deviation and epileptic nystagmus. AB - We studied an 11-year-old boy with focal seizures in the right temporo-occipital cortex. During the seizure, there was a 1- to 2-second period of ipsiversive (rightward) conjugate eye deviation, followed by 10 to 15 seconds of horizontal jerk nystagmus with slow phases that were directed to the right and appeared linear. The patient was conscious throughout the seizure. These findings fit the description of epileptic nystagmus. We postulate that the eye deviation and slow phases of the nystagmus in this patient were induced by epileptic activation of a cerebral smooth pursuit pathway originating from temporoccipital cortex. PMID- 2320243 TI - Localizing the site of magnetic brain stimulation in humans. AB - Magnetic stimulation of the human brain is performed in clinical and research settings, but the site of activation has not been clearly localized in humans or other species. We used a set of magnetic stimulus coils with different field profiles to isolate movement of single digits at motor threshold and to calculate corresponding electric field strengths at various distances beneath the scalp. Two coils could produce the same electric field intensity at only 1 point. Thus, we could estimate the depth of stimulation by finding the intersection of the electric field plots, which were then superimposed on MRIs of the underlying brain. In each of 3 subjects the field plots intersected at the crown of a gyrus, in the region of the central sulcus, an near the level of the gray-white junction. This position and the electric field orientation support localization to layer VI of cerebral cortex. PMID- 2320244 TI - Presymptomatic and prenatal diagnosis in myotonic dystrophy by genetic linkage studies. AB - Myotonic dystrophy (DM) is an autosomal dominant disorder with age-dependent penetrance and extremely variable expressivity. With the genetic markers CKMM and ApoC2, both of which are tightly linked and centromeric to DM, presymptomatic and prenatal diagnosis for myotonic dystrophy is available. We present the results of 4 families tested for carrier status of myotonic dystrophy by genetic linkage studies and define potential limitations of these studies. A protocol for genetic linkage studies in DM is outlined. PMID- 2320245 TI - Abnormal respiration and sudden death during sleep in multiple system atrophy with autonomic failure. AB - We studied respiration during sleep in 7 patients with multiple system atrophy and autonomic failure (MSA-AF) and 7 control subjects. Although mean respiratory rate, tidal volume, and inspiratory flow rate were statistically similar in both groups, the coefficients of variability in all were significantly greater in MSA AF patients. Four of 5 nontracheostomized had evidence of upper airway obstruction without significant oxygen desaturation. Three of these 5 patients died suddenly during sleep. MSA-AF is associated with upper airway dysfunction and disordered central respirations which can be life threatening. Evidence of even mild obstruction during sleep should warrant tracheostomy. PMID- 2320246 TI - The pretectal syndrome: 206 patients. AB - The pretectal syndrome occurred in 2.3% of patients personally examined over an 18-year period. The symptoms were nonspecific, but the signs (abnormal pupils in 198 patients, vertical gaze limitation in 180, disjunctive horizontal eye position in 90 and vertical in 79, lid retraction in 83, and convergence retraction nystagmus in 71) were exquisitely localizing. The etiology, skewed by the local prevalence of cysticercosis, was hydrocephalus in 80 patients, stroke in 53, and tumor in 45. The importance of timely diagnosis was underscored by the relatively good prognosis of many patients. PMID- 2320247 TI - A prospective study of principal care among Colorado neurologists. AB - We initially surveyed the practice patterns of 24 private sector neurologists in Colorado between June and September, 1985, having chosen representative practices from each of 4 practice types (solo [6], nonsolo single discipline [11], nonsolo multispecialty [4], and nonsolo HMO [3]) and from both urban (14) and rural (10) practice locations. Among 2,373 consecutive new patient visits initially surveyed, we reexamined 2,359 (99%) charts 1 year later to investigate patterns of principal care. We defined principal care as 2 or more follow-up visits in the year following the initial office visit. One-fifth of initial visits received principal care, and the mean number of follow-up visits per year among those receiving principal care was 4 (range, 2 to 32 visits). The best indicators of principal care were Medicare coverage, a classic neurologic diagnosis (seizure, stroke), rural practice location, and solo neurology practice. The best indicators of consultative care were self-pay coverage, a diagnosis of musculoskeletal, psychiatric, or pain disorder, urban practice location, and HMO neurology practice. Age, sex, race, and type of referring physician were unimportant in determining subsequent principal care. Projections of future manpower needs must reflect both consultative as well as principal care services provided by neurologists, as well as the cost-effectiveness of such care. PMID- 2320248 TI - Stretch syncope in adolescence. AB - We describe 6 adolescents with syncope induced by stretching with the neck hyperextended. Studies of the cardiovascular responses to stretching and Valsalva in these patients were the same as controls, indicating that the mechanism is not simply Valsalva but may also involve vertebral artery compression coupled with a familial tendency to faint. PMID- 2320250 TI - Striatonigral degeneration: clinical, MRI, and pathologic correlation. AB - We report a patient with striatonigral degeneration in whom T2-weighted MRI imaging revealed low signal and atrophy in the putamen. Neuropathologic studies confirmed putaminal atrophy and iron deposition in the MRI low signal regions. PMID- 2320249 TI - Blood pressure and plasma catecholamines in never-treated parkinsonian patients: effect of a selective D1 agonist (CY 208-243). AB - We found blood pressure (BP), heart rate (HR), plasma norepinephrine (NE), and epinephrine (E) levels in the lying and the standing positions to be similar in never-treated parkinsonian patients (stages 1 and 2) and age-matched controls. CY 208-243, a new centrally active D1 agonist, significantly decreased BP, HR, and NE (but not E) values in the lying position; it elicited orthostatic hypotension and blunted the rise in NE elicited by standing up. These results indicate that the early stages of Parkinson's disease are not accompanied by major changes in autonomic cardiovascular function and suggest the involvement of central D1 receptors in the control of sympathetic tone. PMID- 2320251 TI - Vertical ocular motor apraxia. AB - We report a case of vertical ocular motor apraxia in a 4-year old boy whom we have followed for 2 years. The patient had no upward and downward voluntary movements of the eyes since birth, but horizontal movements were normal. He achieved gaze changes in the vertical plane by combined blinks and head movements. Magnetic resonance imaging demonstrated bilateral lesions at the mesencephalic-diencephalic junction. PMID- 2320252 TI - Arachnoiditis ossificans with arachnoid cyst after cranial tuberculous meningitis. AB - A 34-year-old woman developed symptomatic arachnoiditis ossificans and an arachnoid cyst as a consequence of tuberculous meningitis adequately treated 20 years before. Surgical decompression of the cyst stopped the progression of her spastic paraparesis. Pathologic examination confirmed the presence of ossification of the arachnoid. PMID- 2320253 TI - CCK-8S inhibits L-dopa-induced dyskinesias in parkinsonian squirrel monkeys. AB - Systemic administration of CCK-8S (1 or 10 micrograms/kg IP) markedly inhibited L dopa-induced dyskinesias in parkinsonian monkeys, but did not interfere with locomotor stimulation by L-dopa. CCK analogues may be useful antidyskinetic agents for improved control of Parkinson's disease. PMID- 2320254 TI - Noncommunicating syringomyelia in multiple sclerosis: detection by magnetic resonance imaging. AB - We report 3 patients in whom multiple sclerosis appeared to be complicated by noncommunicating syringomyelia. Despite modest or minimal signs of myelopathy, each patient had cavitary spinal cord lesions detected with MRI. MS may be associated with noncommunicating syringomyelia. PMID- 2320255 TI - Central dazzle in trigeminal sensory neuropathy. PMID- 2320256 TI - Rarity of EEG photo-paroxysmal and photo-myogenic responses following treated alcohol-related seizures. PMID- 2320257 TI - Copper diseases. PMID- 2320258 TI - Treatment of Parkinson's disease. PMID- 2320259 TI - Seizures and compression fracture. PMID- 2320260 TI - MS prevalence in Spain. PMID- 2320261 TI - Boxer's encephalopathy. PMID- 2320262 TI - Bruxism. PMID- 2320263 TI - Comment on the AAN thermography report. PMID- 2320264 TI - Tardive oculogyria. PMID- 2320265 TI - Polio vaccine and BGS. PMID- 2320266 TI - American Academy of Neurology. 42nd annual meeting program. Miami Beach, Florida, April 30-May 6, 1990. Abstracts. PMID- 2320268 TI - Cystic degeneration following severe spinal trauma. Clinical observations in 30 patients. AB - Secondary, in most cases ascending neurological deterioration following severe spinal trauma has been known since the beginning of this century. The alterations are caused by cystic cord degeneration and probably are due to venous circulatory disturbances. In a review of the literature 680 cases were found. The present paper describes findings in our 30 patients. Modern diagnostic methods provide exact localization and evaluation of the cysts. These can then be drained microsurgically. Short-term success is good in many cases, long-term developments will be observed carefully. The functional loss of only one segment can, depending on the level of the original lesion, result in dramatic consequences for the patient. PMID- 2320267 TI - Surgical treatment of patients with midline arachnoid cysts. AB - Usually, arachnoid cysts are found in the Sylvian fissure (about 85%); midline arachnoid cysts are rare. Typical clinical symptoms are increased intracranial pressure, caused by a concomitant hydrocephalus, as well as visual and/or endocrinological disturbances. Six patients were examined, treated with one of two different surgical methods (cyst shunting or open treatment, either craniotomy/cyst membrane resection or laser endoscopy). Better results were observed following open treatment methods. PMID- 2320269 TI - Surgical treatment of intramedullary tumors (spinal cord and medulla oblongata). Analysis of 16 cases. AB - From February 1987 to July 1988, 16 patients of our clinic with intramedullary tumors (seven astrocytomas, six ependymomas, two angiomas with intramedullary hematomyelia, and one angioblastoma of the medulla oblongata) underwent surgery. Radical excision was possible in six cases with tumors in the cervical and/or thoracic region as well as in two cases with tumors in the medulla oblongata. In the group of patients with cervical and/or thoracic tumors, seven showed improvement, up to complete remission of the neurological symptoms. From eight patients with tumors of the medulla oblongata, one patient showed an invasive tumor of the medulla oblongata and pons with corresponding extensive neurological deficits, and died six weeks after surgery. The neurologic symptoms of the other seven patients improved after a postoperative interval of at least six weeks. The surgical approach to tumors of the medulla oblongata or spinal cord was performed by midline incision. Occasionally, a dorsal root entry zone (DREZ) incision was used when the tumor showed strictly unilateral localization. Tumors of the rhomboid fossa were approached by a lateral incision to avoid damage to nuclear structures. The more rostral the tumor localization (medulla oblongata, pons), the less complete was the surgery: only one ependymoma of the medulla oblongata was accessible to total extirpation. The tumor dignity worsened with ascending level of tumor localization. As described generally in the literature, neurological deficits of those patients with tumors in the medulla oblongata increased in the first few postoperative weeks before they began to improve. Chemotherapy, radiation therapy or decompressive laminectomy by themselves only lead to an improvement and are, therefore, not recommended. PMID- 2320270 TI - Diseases of the vertebral arteries. AB - Case reports and postmortem neuropathological findings of a wide spectrum of diseases affecting the vertebral arteries, in particular vasculitis, traumatic lesions, degenerative changes and congenital abnormalities, are discussed. PMID- 2320271 TI - Intramedullary vascular lesions in the high cervical region: transoral and dorsal surgical approach. Two case reports. AB - Intramedullary vascular malformations in the high cervical region are extremely rare. Two young adult patients with vascular lesions at the level C 2 and 3, and C 2-4 are reported. In one patient selective spinal angiography revealed a combined malformation with a ventral intramedullary arteriovenous angioma and a premedullary aneurysm. This malformation was approached and removed transorally after spondylectomy of C 2. In the second patient MRI and selective angiography showed an intramedullary hemangioblastoma extending from C 2-C 4. After embolization, this lesion was surgically removed via a dorsal approach. Both patients suffered from severe neurological deficits preoperatively. MRI and selective angiography showed the exact locations of the tumors within the spinal cord and indicated a transoral approach in one case and a dorsal approach in the other. After complete obliteration and removal of the lesions, the patients showed no neurological deficits and returned to their previous professions. PMID- 2320272 TI - Syndrome of the posterior and anterior root in a late isolated CNS relapse of c ALL. Case report. AB - A 15 year-old girl who had c-ALL diagnosed in 1982 was presented in our clinic suffering from an ascended flaccid paresis and dysaesthesia of both legs. These are typical symptoms of polyradiculitis of the nerve roots L2-S2. A lumbal puncture revealed a pleocytosis with lymphoblasts which were up to 40% CD10 (cluster of differentiation) up to 70% CD19 and TdT (terminal transferase) positive. The diagnosis of late isolated CNS relapse was made. It is assumed that local residual infiltrations of leukemic cells into the nerve roots L2-S2 got into cell cycle and caused these rare CNS leukemia symptoms. Therefore the value of a craniospinal irradiation to prevent a CNS and systemic relapse is discussed. PMID- 2320273 TI - Pyomyositis: an unusual complication of Staphylococcus aureus infection. AB - Pyomyositis, an unusual complication of Staphylococcus aureus infection. Treatment consists of surgical drainage and antibiotics. PMID- 2320274 TI - Mesenteric venous thrombosis caused by deficiency of physiologic anti-coagulants: report of a case. AB - Mesenteric venous thrombosis is a clinical entity, which is rarely recognized on admission. The patients are admitted with vague abdominal complaints and, eventually, abdominal sepsis might occur requiring laparotomy. Nowadays, underlying hypercoagulable states such as antithrombin-III, protein-C and protein S deficiencies are recognized more frequently as a distinct cause of mesenteric venous thrombosis. In this paper, a case of mesenteric venous thrombosis due to protein-C deficiency is presented. The patients generally have a history of thromboembolism of the deep veins of the legs at young age. The combination of vague abdominal complaints and a history of thrombosis of the deep veins of the legs should arouse the suspicion of mesenteric venous thrombosis. In these cases, contrast-enhanced computerized tomography is a non-invasive diagnostic means which may provide the diagnosis. If infarction of the gut is present, resection is mandatory and a second-look operation should be performed. After surgery, heparinization is essential. This must be followed by administration of oral anticoagulants for an indefinite period in case of an underlying antithrombin III, protein-C or protein-S deficiency. PMID- 2320275 TI - Carpometacarpal dislocation: report of three cases. AB - The case reports of three patients with carpometacarpal dislocations are described. The diagnosis of this condition may be difficult and is often missed. Swelling, dislocation and a palpable lump are the main clinical findings. X-ray findings, the key to the diagnosis, are loss of parallelism, interruption of the so-called M-line and overlapping of articular surfaces. Additional X-rays in different planes are to be recommended if carpometacarpal dislocation is suspected. PMID- 2320276 TI - Extended lymph-node dissection for gastric cancer: a challenge for better survival results. AB - Most Japanese studies have better survival results for gastric cancer after surgery compared to the results reported by Western authors. Japanese surgeons trace their success to early detection and extended lymph-node dissection. Analysis of data from several Japanese and Western surgical departments could not substantiate factors other than the surgical procedure as an explanation for the better survival rates in advanced gastric cancer in Japan. Whether extended lymph node dissection actually improves survival results or merely rectifies classification which influences stratified survival results, remains to be justified. A prospective randomized study, comparing the Japanese R2 with R1 resection, is initiated in The Netherlands to answer this question. For this purpose we describe the surgical strategy and operative technique of the extended lymph-node procedure. PMID- 2320278 TI - [Art in the fight against AIDS]. PMID- 2320277 TI - The Belsey Mark-IV procedure in gastro-esophageal reflux and hiatal hernia. AB - The long-term results were assessed of 75 patients, who underwent 76 Belsey Mark IV operations for disabling symptoms of gastro-esophageal reflux and hiatal hernia. The mean follow-up of the patients was 4.5 years (range 1-10 years). All reflux symptoms resolved in addition to normal gross endoscopic appearances in 87 per cent of the patients. The complications were minimal and the side effects few. PMID- 2320279 TI - [Peptic ulcer and liver cirrhosis. Clinico-epidemiologic considerations]. AB - A significant increase in associated liver disease has been confirmed in duodenal ulcer cases, with various studies showing a 5-14% incidence of the ulcers in patients with cirrhosis. The present study was undertaken to discover the incidence of peptic ulcer in such patients, to investigate a series of epidemiological data in a group cirrhosis patients with ulcers and to establish an adequate protocol for the treatment of the ulcer in both its acute and post healing stage. The incidence of peptic ulcers in cirrhosis patients was calculated in a retrospective study of 377 hospitalised patients in two consecutive years (1986, 1987). The epidemiological data are based on 99 of them. Acute ulcer treatment was given in 31, while 41 with healed ulcers were put on maintenance therapy. Ulcers were found in 16-17% of the cirrhosis patients; the cirrhosis was caused by alcohol abuse in 61.53% and was post-necrotic in 21.79%. Endoscopy revealed duodenal ulcers in 60.6%, gastric ulcers in 32.3%. In this sample, 39.39% were non-smokers, while 23.23% smoked over 20 cigarettes a day. PMID- 2320280 TI - [Prognostic value of the ratio of bone marrow plasma cells in multiple myeloma]. AB - The relationship between initial percentage of bone marrow plasma cells and survival was studied in a group of 70 patients affected with multiple myeloma. All patients had a complete follow-up. The initial percentage of plasma cells shows a highly significant correlation with survival. Moreover, the percentage of bone marrow plasma cells is also correlated with the levels of hemoglobinemia and serum or urinary monoclonal component. The patients were divided in three groups according to the percentage of bone marrow plasma cells: group A: less than 20%; group B: 21-40%; group C: greater than 41%. The mean survival times of these three groups are significantly different, as well as their survival curves. The initial percentage of plasma cells in bone marrow is an useful parameter for estimating survival and predicting prognosis, and it can be an additional factor in the clinical staging of multiple myeloma, while the effectiveness of therapy can be monitored by sequential bone marrow aspirates. PMID- 2320281 TI - [Multitest evaluation of the immune status of patients with bronchogenic carcinoma before and after radiotherapy]. AB - Sixty-two patients with lung cancer underwent the multitest before and after radiotherapy so as to assess the initial immune state and modifications induced by radiation therapy. In cancer patients, a significantly smaller number of positive skin reactions were encountered than in the controls. No statistically significant differences emerged between patients grouped on the basis of histotype, clinical stage and performance or otherwise of surgery. In living patients, higher values were observed than in patients who died. After radiotherapy, multitest values underwent a very slight decrease. PMID- 2320282 TI - [The role of inflammatory infiltrate as a prognostic criterion in cerebral metastases. Preliminary results]. AB - Data concerning a preliminary study on the prognostic significance of inflammatory infiltration in cerebral metastases are reported. Seventeen cases of operated cerebral metastases have been studied to investigate their histotype and grade of necrosis, stromal reaction, and inflammatory infiltration. Finally, the results obtained are discussed in relation to the postoperative survival rate of the patients. PMID- 2320283 TI - [Essential thrombocythemia. Case reports and clinico-therapeutic considerations]. AB - A short survey of essential thrombocythaemia is made and some diagnostic and therapeutic aspects of the disease and personal clinical experience are discussed. PMID- 2320284 TI - [Heterozygote beta-thalassemia and neoplastic pathology]. AB - To evaluate the possible correlation between heterozygote beta thalassemia (BTE) and neoplastic disease, a 5-year personal experience of clinically followed patients at Comacchio Hospital Internal Medicine and Surgery divisions is presented. The hemoglobin A2 was assayed in all patients whose medial corpuscular volume was lower than 80 fl. 589 consecutive neoplastic patients were evaluated; of these 73 were BTE. In the BTE patients the prevalence of neoplastic disease was 12.39% higher than in healthy people (8.8%, chi 2 = 8.79 and p = 0.03). In thalassaemic carriers the titres of medial annual incidence to 10,000 for neoplastic diseases were proved to be ever higher (46.08 versus 31.49/10,000). The incidence of gastric cancer was found to be greater in BTE than in non-trait carrier population (13 in 63 patients, with a 20.63% prevalence, chi 2 = 9.52 and p = 0.02). A higher prevalence of thalassaemic carriers was observed among subjects with cancer in different organs: larynx, oesophagus, gallbladder and bile ducts, pancreas, breast and kidney, but these differences were not statistically significant. As for various sites of cancer: lung, liver, uterus and ovary, bladder, prostate, skin, lymphomas, leukaemias and gammopathies, no difference in BTE prevalence was found. We conclude that a greater predisposition to neoplastic disease can be present in BTE than in healthy population. PMID- 2320285 TI - [Clinical aspects of respiratory pathology in scleroderma. Case reports]. AB - Six cases of scleroderma with pulmonary involvement, either isolated or accompanied by other visceral signs, observed between 1985 and 1987 have been examined. Patients were undergoing treatment with cortisone drugs in 4 cases and azathioprine in 2. Chest X-ray documented a picture of nodular opacities in 3 cases, reticular in 2 and miliariform in 1. B.A.L. revealed a picture of prevalently neutrophil alveolitis in all subjects, while transbronchial biopsy showed a finding of macrophagic infiltration in 2 cases, and one of fibroblastic proliferation in 4. The anatomoclinical damage was reflected adequately by spirometric tests and above all by the DLCO, while Gallium 67 scan and measurement of the A.C.E. were not very sensitive. PMID- 2320286 TI - [Bleeding of gastric ulcers. Epidemiologic, clinical and functional characteristics]. AB - The frequency of gastrointestinal haemorrhage due to gastric ulcer has been assessed in 254 personally observed patients suffering from this endoscopically verified pathology. 56 patients, namely 22% of the cases, presented haematemesis and/or melena of the ulcerative lesion. This subgroup was compared with 65 patients with endoscopically verified gastric ulcer without previous bleeding episodes from the lesion in their clinical history, in respect of certain epidemiological, clinical and biohumoral features. The purpose of the study was to check the possible existence of clinical and/or physiopathological differences between subjects with bleeding gastric ulcer and the population of non-bleeding ulcer patients. In 80% of patients studied, the gastric ulcerous disease started with digestive haemorrhage and it was not accompanied by dyspeptic-painful symptomatology in 20% of cases. The pain symptomatology does not appear to be influenced by the intake of non-steroid anti-phlogistic drugs. No significant difference emerges between the two groups considered as regards epidemiological features and biohumoral data (PG I, gastrin, B.A.O. and M.A.O.). PMID- 2320287 TI - [Therapeutic treatment of drug dependence during hospital recovery]. AB - The purpose of the research was to ascertain whether hospitalization makes it easier to treat heroin addiction and to what extent. Eighty-six subjects hospitalised in two Turin hospitals were considered. Two different therapeutic protocols were applied. Results obtained are discussed and some interpretation of resulting data are advanced. PMID- 2320289 TI - Penetrating isolation. PMID- 2320288 TI - [Tuberculosis in Bergamo Province. Statistical estimates for the quadrennium 1984 1987]. AB - The clinical files of patients admitted to the Ospedali Riuniti of Bergamo between January 1984 and December 1987 in which the presence of mycobacteria has been demonstrated have been reviewed. We have analysed the clinical pattern and the complicating diseases and we have reported the typing of mycobacteria in comparison with the literature data. We stress the danger of mycobacterial infections particularly in patients who are in an immunodepressed state. PMID- 2320290 TI - Alone at last. PMID- 2320291 TI - Stopping by. PMID- 2320292 TI - A touch of heart. PMID- 2320293 TI - Hepatitis B--a work-related hazard? PMID- 2320295 TI - Beware of misleading labels. PMID- 2320294 TI - 7 ways to cure communication breakdowns. PMID- 2320296 TI - Guidelines for administering i.v. drugs. PMID- 2320297 TI - Learning to care for Junior. PMID- 2320298 TI - How to write nursing diagnoses. PMID- 2320299 TI - A manager's guide to overtime pay. PMID- 2320300 TI - Action stat! Hypertensive crisis. PMID- 2320301 TI - Dosage error. PMID- 2320302 TI - Going face to face with fear. PMID- 2320303 TI - Zeroing in on chest pain. PMID- 2320304 TI - Acute head injury. PMID- 2320305 TI - How to perform basic airway management. PMID- 2320306 TI - Cancer update 90. Pain management--up the ladder. How chemotherapy stops cancer cell growth. PMID- 2320307 TI - Strategies for handling angry patients--and their families. PMID- 2320308 TI - Understanding therapeutic plasma exchange. PMID- 2320309 TI - Assessing groin pain after an arteriogram. PMID- 2320310 TI - Myths & facts ... about peritoneal dialysis. PMID- 2320311 TI - The specialist psychiatric nurse. PMID- 2320312 TI - The specialist in tissue viability. PMID- 2320313 TI - Strength, status and respect. PMID- 2320315 TI - Up, up and away. PMID- 2320314 TI - How nursing is all a matter of degrees. PMID- 2320316 TI - Nicaragua's responses to its health problems. PMID- 2320317 TI - Women now at high risk from AIDS. PMID- 2320318 TI - Men can care, too! PMID- 2320319 TI - The CNS in intensive care. PMID- 2320320 TI - The midwife and foetal medicine. PMID- 2320321 TI - Pain control in labour. PMID- 2320322 TI - More than a lot of hot air. PMID- 2320323 TI - Qualified success? PMID- 2320324 TI - Responding to refugees. PMID- 2320325 TI - The CPN and eating disorders. PMID- 2320326 TI - Measuring wound size. PMID- 2320327 TI - The need for staff support. PMID- 2320328 TI - Coping with trauma. PMID- 2320329 TI - A no-touch technique. PMID- 2320330 TI - [The midwives' charter in Quebec]. PMID- 2320331 TI - [The transvenous temporary pacemaker]. PMID- 2320333 TI - [Current therapeutic technics in urinary incontinence]. PMID- 2320332 TI - [Lea's secret. Confidentiality at any cost?]. PMID- 2320334 TI - [Self administration of intravenous antibiotics at home]. PMID- 2320335 TI - [Sophie receives new bone marrow from her brother]. PMID- 2320336 TI - The stability of high blood pressure in Dunedin children: an eight year longitudinal study. AB - Resting blood pressures were recorded for children in the Dunedin Multidisciplinary Health and Development Study at two year intervals five times from age seven to fifteen. Correlations between pairs of readings were modest but significant, and higher for systolic (0.39 to 0.62) than for diastolic blood pressure. However, although children with normal blood pressure were likely to continue to have normal blood pressure, high blood pressures at age seven, nine, eleven and thirteen were not stable--only 28% of those whose systolic blood pressure at age seven was in the highest 5% had two subsequent readings in the highest 5%. On the other hand 56% of those in the highest 20% had two subsequent readings in the highest 20%, and 9% had all subsequent readings in the highest 20%. We do not believe that adult essential hypertensives can be recognised early by annual blood pressure measurement in childhood and the assignation of blood pressure rank according to a set of normal values. PMID- 2320337 TI - Serious unintentional injuries associated with architectural glass. AB - Injuries associated with architectural glass have become a matter of considerable concern in recent years. Despite this concern there has been no attempt to document either the extent of the problem in New Zealand or the circumstances under which these events occur. In this study, national injury mortality data for the period 1977-86 were examined and cases selected if the cause of death was attributable to an event involving architectural glass. A total of nine deaths were identified. All discharges from New Zealand public hospitals during 1986 were examined to identify victims who had been treated for injuries associated with architectural glass. Descriptive information contained on each patient record was coded to provide more specific information on the circumstances of injury. A total of 501 first admissions to hospital were identified, giving an incidence rate of 15 per 100,000 persons per year. The highest rate of 60 per 100,000 per year, was found for males in the age group 15-24 years. Seventy-eight percent of the events involved males, 62% occurred at home, 64% involved windows, and 32% involved doors. Ninety-three percent of the injuries were open wounds. Seventy-nine percent of the injuries were to the upper limbs, 13% were to lower limbs and 5% were to the head. The mean length of stay in hospital was 3.3 days. Opportunities for injury prevention are discussed including visual and physical barriers, mandatory glazing standards and public education. Specific areas requiring further research are identified. PMID- 2320338 TI - Cyclosporin therapy for steroid resistant nephrotic focal glomerulosclerosis. AB - A young man with focal glomerulosclerosis and severe steroid resistant nephrotic syndrome was treated with oral cyclosporin for six months without histological evidence of drug induced nephrotoxicity. A marked and sustained partial remission of the degree of proteinuria one year following cessation of treatment was not accompanied by a deterioration in renal function. Cyclosporin may have a role, as yet not fully defined, in the treatment of steroid-resistant or dependent nephrotic syndrome. PMID- 2320339 TI - Epidemiological factors in postneonatal mortality in New Zealand. AB - Nine hundred and sixty-two postneonatal deaths for 1981-83 were matched to their birth registration forms. Deaths were divided into three categories, sudden infant death syndrome (SIDS) 65.4%, other preventable, 12.8%, and nonpreventable causes, 21.8%, to determine the rates of death as related to known and available risk factors. The risk factor profile for other preventable causes and SIDS was similar, the only exceptions being that other preventable causes showed no north south gradient and had a higher incidence in the neonatal period (31.2% v 4.7% for SIDS). The most important risk factors for other preventable causes were found to be the mother being Maori (RR 4.35, CI 3.12-6.06), having a low birth weight infant (RR 3.56, CI 2.07-6.13) and being unmarried (RR 3.45, CI 2.47 4.82). These risk factors point to the possibility of selectively targeting of interventions both prenatally as well as postnatally for those who are at high risk. PMID- 2320340 TI - Dissecting aneurysm of coronary artery presenting as cardiac tamponade. AB - Primary dissecting aneurysm of the coronary arteries usually presents as sudden death or complications of myocardial infarction. The most common site of the dissection has been the anterior descending branch of the left coronary artery. A Chinese woman with primary dissecting aneurysm of the right coronary artery presenting as cardiac tamponade is reported. This is the first case of ruptured coronary aneurysm reported in the Chinese and the only case presenting as cardiac tamponade since 1931. PMID- 2320341 TI - Selenium content of foods consumed in Otago, New Zealand. AB - Selenium (Se) concentrations were determined in over 600 foods sampled in Dunedin, New Zealand. Foods included those produced in the region, foods which were expected to contribute significantly to the total Se intake, breads and other wheat products which might be affected by the importation of Australian wheat, and imported vegetarian foods. Foods with the highest Se concentrations were brazil nuts, sunflower seeds and all varieties of fish and kidneys. Somewhat lower concentrations were found in liver, pork, chicken, eggs, cashew nuts, soybeans and mushrooms. Vegetables, fruits, cereals and milk products were generally low in Se with the exceptions of mushrooms, imported legumes, rice and bananas. Those foods showing the greatest difference in Se content from those of other countries were cereal products and meat foods. The effect of a number of cooking methods on Se concentrations indicated that in general, little Se was lost during cooking. The importation of a shipment of high-Se wheat from Australia in 1984 raised Se concentrations in breads and other wheat products two to four fold. PMID- 2320342 TI - Cigarette smoking and absence from work. PMID- 2320344 TI - Costs and availability of alcoholism therapy and liver transplantation. PMID- 2320343 TI - First month with the new ACC regulations. PMID- 2320345 TI - Ethnic differences. PMID- 2320346 TI - Generic practice. PMID- 2320347 TI - Treatment protocols. PMID- 2320348 TI - OSHA reviews bloodborne disease standard. PMID- 2320349 TI - Health-care planners, physicians must cooperate to stem rising costs. PMID- 2320350 TI - Work-place stretching programs reduce costly accidents, injuries. PMID- 2320351 TI - Emergency medical response teams react swiftly to Phillips plant tragedy. PMID- 2320352 TI - Rules changes, worker training help simplify fall prevention. PMID- 2320353 TI - Ocular symptomatology in familial hypomelanosis Ito. Incontinentia pigmenti achromians. AB - Hypomelanosis Ito (HI) is a very rare neurocutaneous syndrome which is often associated with cutaneous, cerebral, musculoskeletal and ocular abnormalities. The paper deals with changes in familial HI (mother and daughter) with special consideration of ocular symptomatology; it also presents a review about the relevant literature published to date--not documented with photographs with one exception. The argument is raised whether all ocular changes described in HI actually belong to the syndrome or are partly a mere coincidence. There is also a description of a cataract which has never been observed in cases of HI. Electrophysiological tests (electroretinography, electro-oculography, visual evoked potential) which to date have not been carried out for HI, are presented and their results reported. Mention is also made of the hereditary factor which has so far been questioned; it is assumed that it is autosomal dominant in character. In this context, the results of a chromosome analysis in both mother and daughter are presented. PMID- 2320354 TI - [Squint operations for impaired motility due to endocrine ophthalmopathy]. AB - In every case of an uncertain vertical diplopia one should think of an endocrine ophthalmopathy. A squint operation done in time will improve the motility of the eye. 8 of our 9 patients had no longer a diplopia after surgery and got binocular vision. 6 months after stabilization of the endocrine situation we resected and recessed the rectus muscles, especially the vertical rectus muscles, in 1 case we advanced the inferior oblique muscle. The amount of the surgical correction depended on the motility disturbance and the angle of squint which we compensated a few days before the operation by means of prisms. Postoperatively the patients got steroids parenterally. PMID- 2320355 TI - The relationship of mean defect to corrected loss variance in glaucoma and ocular hypertension. AB - Statistical analysis of visual-field data is permitted by the quantitative techniques used in automated perimetry. The visual-field indices mean defect (MD) and corrected loss variance (CLV) provide an opportunity to analyze and follow visual fields mathematically. We investigated the relationship of MD to CLV in 32 glaucoma suspects and 17 patients with visual-field defects due to chronic open angle glaucoma. In glaucoma patients with early and moderate disease (up to a MD of 18 dB), the CLV statistically covaried with the MD (R2 = 0.85). Beyond an MD of 18 dB, increases in the MD seemed to cause a decline in the CLV. These results differ from prior reports on the relationship of MD and CLV. Reasons for this and implications for the use of these statistics in the clinical management of the glaucoma patient are discussed. These results may be helpful in the understanding of the pathophysiologic basis of damage in glaucoma. PMID- 2320356 TI - C wave study in optic neuritis due to demyelinating disease. AB - The C wave was recorded from 20 eyes suffering from neuritis due to demyelinating disease and in 5 eyes showing optic atrophy due to trauma or to increased intracranial pressure. Our results show that in cases with optic neuritis the C wave amplitude was clearly lower than normal. It is interesting that in the other 'healthy', at least clinically, eye the C wave was subnormal too. On the contrary, in the eyes with optic atrophy the C wave was normal. These findings are against the possibility of an efferent neuronal pathway involvement, which influences the level of the retinal pigment epithelium, and support the view of its involvement during the course of the demyelinating disease that causes the optic neuritis. PMID- 2320357 TI - Effects of sodium iodate on experimental subretinal neovascularization in the primate. AB - We investigated the role of the retinal pigment epithelium (RPE) in the development of subretinal neovascularization (SRN) induced by bilateral laser photocoagulation of the retinas in monkeys. RPE function was affected by a unilateral carotid injection of sodium iodate, a selective RPE toxin, before laser photocoagulation. This caused severe RPE damage in the ipsilateral eye, but did not affect the contralateral eye. After laser photocoagulation no SRN was demonstrable clinically or histopathologically in the ipsilateral eye; in contrast, active SRN showing extensive fluorescein leakage was found in the contralateral eye. These results suggest that RPE may play a role in the development of laser-induced SRN. PMID- 2320358 TI - One-piece contact lens for laser iridotomy at iris base by argon and Nd:YAG laser. AB - Laser iridotomies at the base of the iris provide a free shunt between the anterior and the posterior chamber remote from the capsule of the lens. Injury to the lens capsule by the Nd:YAG laser is avoided as the iris is not in close apposition. The heterocentric applanatic lens guides the laser beam under the limbal shelf toward the root of the iris. The combined use of a thermal and an ionizing laser is preferred. PMID- 2320359 TI - An investigation of the difference in stereoacuity between crossed and uncrossed disparities using Frisby and TNO tests. AB - Is stereoacuity better, on average, with a crossed test disparity? To answer this question, 15 subjects with good stereoacuity performed Frisby and TNO stereotests with test plates in each of 2 possible orientations, crossed and uncrossed. Stereoacuities and response times were measured. The answer was that a subject's stereoacuity with crossed and uncrossed disparity could be different, e.g., 30 and 480 sec arc, respectively, but that, on average, a crossed disparity was no easier to detect than an uncrossed one. There were more and greater differences with the TNO than with the Frisby test and Frisby stereoacuity was, on the average, 4 times better. It is recommended that tests which can have two orientations be tested in both and the best result taken as the stereoacuity. PMID- 2320360 TI - Color vision characteristics of visually impaired children. AB - A classroom assessment of color vision characteristics of children with low vision was conducted using a battery of tests. The results showed 75% of the children failed one or more tests, although only 24% had a moderate or severe color vision defect. Comparisons with the low vision clinic color vision assessment showed that many of the children were not identified as being color vision defective. Considering the use of color-coded information in education, greater emphasis on color vision evaluations in routine low vision examinations is recommended. PMID- 2320361 TI - Investigation of central visual fields in patients with age-related macular changes. AB - The effect of early macular pigmentary and drusen changes on the central visual field was investigated in elderly patients with normal visual acuities. Visual field measurements were taken with the Humphrey Field Analyser using its 24-2 and 10-2 full threshold programs. No significant differences were found between two patients groups, one with and one without the macular changes. We conclude that fine pigmentary changes and hard drusen do not cause changes in visual functioning and can be accepted as normal age-related changes. PMID- 2320362 TI - Predicting visual acuity from detection thresholds. AB - Visual performance based exclusively on high luminance and high contrast letter acuity measures often fails to predict individual performance at low contrast and low luminance. Here we measured visual acuity over a wide range of contrasts and luminances (low mesopic to photopic) for 17 young normal observers. Acuity vs. contrast functions appear to fit a single template which can be displaced laterally along the log contrast axis. The magnitude of this lateral displacement for different luminances was well predicted by the contrast threshold difference for a 4 min arc spot. The acuity vs. contrast template, taken from the mean of all 17 subjects, was used in conjunction with individual spot contrast threshold measures to predict an individual's visual acuity over a wide range of luminance and contrast levels. The accuracy of the visual acuity predictions from this simple procedure closely approximates test-retest accuracy for both positive (projected Landolt rings) and negative contrast (Bailey-Lovie charts). PMID- 2320363 TI - Association of giant papillary conjunctivitis with seasonal allergies. AB - Giant papillary conjunctivitis (GPC) is largely a soft contact lens-related syndrome, characterized by the formation of giant papillae on the upper tarsal conjunctiva, itching, excess mucus, erythema, and contact lens intolerance. In response to the suggestion that GPC occurs more frequently in atopic individuals, a retrospective study was designed in order to determine the months in which patients were diagnosed with GPC during 1987 and 1988. Personal histories of allergy were also recorded for these patients, and compared to an age- and sex matched control group. Significant peaks in the number of patients diagnosed with GPC occurred in the spring, and especially in late summer/early fall of both years. In addition, the GPC patients reported significantly more overall allergies than did the control group. However, a breakdown of the individual allergy data revealed that only allergies to contact lens solutions, specifically thimerosal, were significantly higher in the GPC group. Reported allergies to medications and pollen were also elevated in the GPC patients, but not significantly. The seasonal onset of GPC diagnoses in 1987 and 1988, and the increase in reported allergies within the GPC group, suggests a strong association between atopy and the development of GPC. PMID- 2320364 TI - In vivo dehydration of disposable (Acuvue) contact lenses. AB - The in vivo dehydration of the Acuvue disposable contact lens was measured in six subjects using a contact lens refractometer. On average, the lenses dehydrated 6.2 +/- 1.9% after 20 min and 10.2 +/- 3.9% after 6 h of wear. The magnitude of dehydration is greater than has been reported for other hydrogel lens types of similar water content. This information may assist practitioners in the interpretation of clinical signs pertaining to lens behavior and associated patient symptoms. PMID- 2320365 TI - Intraocular pressure in a healthy population: a survey of 751 subjects. AB - Intraocular pressure (IOP) in a healthy population residing in the urban area of Naples, Italy was measured. The IOP was recorded in the early morning. A total of 751 subjects (367 men and 384 women) (1502 eyes) was examined twice on two different days using a Goldmann tonometer mounted on a Haag-Streit slitlamp. Age ranged from 6 to 89 years. We found a slight and not significant IOP increase with age and that the age-related IOP increase was more evident in women. PMID- 2320366 TI - Predicting the academic performance of Asian, black, and Hispanic optometry students. AB - As optometry schools receive increasing numbers of Asian, Black, and Hispanic applications, it is appropriate for us to ask whether minority students differ in meaningful ways from nonminority students in measures used in admissions, and whether these variables have differential validity in predicting their achievement in optometry school. This study compares Asian, Black, Hispanic, and nonminority students at entry to the University of Houston College of Optometry (UHCO) from 1981 through 1986 and tests the validity of admissions indices to predict optometry grades, academic dropout, and high-level achievement for these ethnic groups. Although preoptometry grade point average (GPA) was the best predictor of optometry grades for all students, measures of verbal ability were additional predictors for Asian students and, for Black and Hispanic students, ability in study/reading and math were predictors. In addition, personality inventory measures and ratings of the competitiveness of the undergraduate institution were important in differentiating minority academic dropouts from retained students. Suggestions are made for optometry college programs which will enhance the probability of success for minority students. PMID- 2320367 TI - [Surgical complications in colorectal tumors]. AB - Complications of elective surgery on 510 colo-rectal cancer patients are reported. Mortality rate of the operations was 4.9% and complications were observed in 10% of the cases. Intraoperative and early postoperative (10%) as well as late (8.6%) complications have been differentiated. Causes and possibilities for preventing complications are analyzed. PMID- 2320368 TI - [Accessibility of medical documentation and its deficiencies. (Problems of the public health brochure)]. PMID- 2320369 TI - [Fatal pneumonia caused by Salmonella. Questions about diagnosis and therapy]. PMID- 2320370 TI - [Gold salts in the treatment of psoriatic arthritis]. AB - 270 psoriatic arthritis patients were studied retrospectively. 65 patients of them were treated with aurothiomalate. The drug was effective in 62% of aurothiomalate treated patients, in 35% were registrated side effects. These data correspond to the experiences with gold salt treatment in rheumatoid arthritis. Exacerbation of skin manifestation, as a special side effect occurring in psoriatic arthritis patients treated with gold salts isn't a contraindication. PMID- 2320371 TI - Oncogenes and the Nobel Prize. PMID- 2320372 TI - Marked alteration in phosphorylation of the RB protein during differentiation of human promyelocytic HL60 cells. AB - The phosphorylation state of the RB protein was found to change markedly during cell differentiation: most of the RB protein was in a highly phosphorylated 115 kD form in human promyelocytic HL60, erythroleukemic K562 and monocytic U937 cells, but during tumor promoter-induced differentiation, the amount of this form decreased and the amount of an under-phosphorylated 110 kD form of the RB protein increased. Induction of differentiation of HL60 cells by dimethylsulfoxide also induced a similar alteration of the RB protein. However, no alteration in the ratio of the two forms was observed in cell lines such as epidermoid carcinoma A431 and adenocarcinoma MKN-7 that were not induced to differentiate by tumor promoter treatment. The highly phosphorylated form and under-phosphorylated form exhibited different affinity for DNA-cellulose and SV40 large T antigen. PMID- 2320374 TI - Loss of heterozygosity on chromosomal segments 3p, 6q and 11p in human ovarian carcinomas. AB - The genetic events involved in human ovarian carcinoma development are still largely unknown. We have used DNA recombinant technologies to examine the genome of normal and neoplastic tissues from 12 different patients with such tumors. We used cloned DNA sequences homologous to loci showing restriction fragment length polymorphisms on chromosomal segments 3p, 5p, 6q, 11p, or 21q to determine the frequencies of losses of constitutional heterozygosity at these loci in tumor DNAs. Losses affecting loci on 3p, 6q, and 11p were found in a high percentage of the cases examined. In contrast, losses of heterozygosity were not found when we used DNA probes for the other 2 above chromosomal segments. Thus, genetic losses involving chromosomal segments 3p, 6q and 11p occurred at non-random frequencies in ovarian carcinomas, suggesting that inactivation of genes located on these chromosomes played a role in their development. PMID- 2320373 TI - Establishment of human retinal pigment epithelial cell lines by oncogenes. AB - The primary human retinal pigment epithelial cells were transfected with oncogenic sequences derived from viruses and cellular homologues of retroviral oncogenes 'protooncogenes' linked to simian virus 40 (SV-40) and retroviral promoters. Foci of cells were noted between 2 to 4 weeks after transfection. Individual colonies of cells were expanded from cultures transfected with SV-40 virion DNA, SV-40 large T antigen gene, Ha-ras oncogene, human and mouse c-myc and adenovirus E1A gene. Established cell lines tested were positive for the specific oncogene sequences by Southern hybridization and also expressed the protein as assayed by immunofluorescence and immunoblot analysis. Cell lines established with SV-40 large T antigen, and SV-40 virion DNA, exhibited epithelioid morphology up to the 25th passage and later became more rounded. However, all cell lines established with other oncogenes continued to retain epithelial morphology. Functional analysis of the cell lines demonstrated the presence of polarity and the ability to phagocytize rod outer segments, characteristics of retinal pigment epithelial cells. The use of oncogenes with immortalization/transformation potential may allow the establishment of cell lines from ocular tissues for analysing the biochemical basis of a disease like retinitis pigmentosa. PMID- 2320375 TI - Human ltk: gene structure and preferential expression in human leukemic cells. AB - We have isolated the human homolog (hltk) of the murine tyrosine kinase gene ltk from a K-562 human leukemia cDNA library. The deduced protein sequence of hltk is 17 amino acids longer in the juxtamembrane domain and 28 amino acids shorter in the carboxy terminus than that of murine ltk. The partially identical splicing points of hltk to those of c-ros showed a close genetic linkage between the two. In Northern blot analysis of 35 human malignancies, hltk is preferentially expressed in leukemias (10 out of 18 cases) with no cell lineage specificity, but none of 17 nonleukemic neoplasms expressed hltk gene. PMID- 2320376 TI - Retinoic acid causes a decline in TGF-alpha expression, cloning efficiency, and tumorigenicity in a human embryonal cancer cell line. AB - The human teratocarcinoma NTERA-2 cl. D1 (NT2/D1) cell is a cloned multipotential embryonal cancer cell line that differentiates into a neuronal phenotype and other cellular lineages with retinoic acid (RA) treatment. Here we report that mRNA for the transforming growth factor-alpha is expressed in these RA-untreated cells and that RA-treatment results in a reduction of mRNA expression within 24 hr of treatment. In total cellular RNA, TGF-alpha mRNA is not detectable by Northern analysis at 6 days when there is increased expression of the human homeotic genes Hu-1 (Hox 2.1) and Hu-2 (Hox 2.2), known markers of RA response in NT2/D1 cells. RA treatment also causes a marked reduction in cloning efficiency and tumorigenicity of these cells. The addition of TGF-alpha or EGF (epidermal growth factor) protein to RA-untreated NT2/D1 cells augments soft agar cloning under limited fetal calf serum conditions. Blocking monoclonal antibodies directed against the EGF receptor (EGFr) can prevent this augmentation. We conclude that TGF-alpha expression inversely correlates with the state of RA induced differentiation of this human teratocarcinoma cell and that TGF-alpha and EGF proteins are stimulatory growth factors in NT2/D1 cells under these culture conditions. PMID- 2320377 TI - The human basic fibroblast growth factor gene is located on the long arm of chromosome 4 at bands q26-q27. AB - Using in situ chromosomal hybridization, we have mapped the gene encoding the basic fibroblast growth factor to chromosome 4 at bands q26-q27. This location is on the same chromosome as that of a related gene, FGF.5, but on a distinct region. PMID- 2320378 TI - Humoral immune responses of Hereford cattle vaccinated with midgut antigens of the cattle tick, Boophilus microplus. AB - Vaccination of cattle with midgut membrane (GM) antigen derived from the cattle tick, Boophilus microplus, infected with the adjuvant Quil A, resulted in significant increases in total immunoglobulins, mainly in the IgG1 and IgG2 fractions of the serum. Analysis of the anti-GM antibody levels of vaccinated cattle showed that the levels of IgG, IgG1 and complement-fixing antibodies were significantly correlated to protection against infestation with cattle ticks. Anti-GM antibodies of the IgG2 and IgM isotype were not correlated to protection against infestation with cattle ticks. Anti-GM antibodies fixed complement (C') in the presence of GM, larval membrane antigen and live, midgut cells, but not in the presence of live, larval cells. Anti-GM antibodies were able to fix C' equally well in the presence of GM antigen and live, midgut cells. None of the antigens tested activated the alternate pathway of complement under the conditions tested. Levels of anti-GM IgG1 antibodies were used to develop a regression model for predicting levels of protection against infestation with cattle ticks in vaccinated cattle. PMID- 2320379 TI - Stage-specific immunity to Taenia taeniaeformis infection in mice. A histological study of the course of infection in mice vaccinated with either oncosphere or metacestode antigens. AB - The course of Taenia taeniaeformis infection in mice previously vaccinated with antigens prepared from either oncosphere (TtO) or metacestode (TtM) was followed by histological examination of livers from mice killed at various times post infection (p.i.). Distinctly different immune responses occurred in the two groups. Very few cysts were seen at any stage of infection in TtO-vaccinated mice and most of those which were present appeared histologically similar to cysts in control mice. In TtM-vaccinated mice many cysts were present from early in infection but histologically it was apparent that most were dying from 15 days p.i. because the tegument had lost its integrity, and degranulated polymorphonuclear leucocytes were present inside the parasites. These findings support earlier suggestions that stage-specific antigens are expressed in oncospheres and metacestodes. Parasites developing normally were surrounded by a halo of alcian blue staining amorphous acellular material. This material appeared to act as a barrier to attack by host inflammatory cells, and disappearance of this layer signalled death of the parasite. The possibility that the gut acted as a barrier to delay migration of oncospheres to the liver in vaccinated mice was investigated, but no evidence for this could be found. PMID- 2320380 TI - Serum and neutrophils alter the rate of excretory/secretory antigen release by Toxocara canis infective larvae in vitro. AB - Infective larvae of Toxocara canis are well suited for studies of nematode antigen expression in vitro. Larvae were labelled with 3H-glucosamine, an approach permitting dual analysis of antigen quantity and composition. Their excretory/secretory (E/S) glycoproteins were efficiently labelled and antigen identity confirmed by immunoprecipitation, SDS-PAGE and fluorography. Compartmental analysis revealed that common components of Mr 100-120 kD were present in somatic, surface and soluble material. The application of biosynthetic labelling and compartmental analysis of parasite responses in vitro to antibody, complement and neutrophils was tested. Results indicated that test larvae in vitro respond by quantitative rather than qualitative changes in antigen production. Specifically, human serum was shown to raise, and neutrophils depress, the rate of antigen release. The implications of these findings for establishing an in-vitro model for analysis of host/parasite reciprocal adaptive responses are discussed. PMID- 2320381 TI - Differential recognition of microfilarial antigens by sera from immigrants into an area endemic for brugian filariasis. AB - Studies in animal models indicate that antibodies to surface antigens of microfilariae participate in the control of parasitaemia resulting from infections with lymphatic filarial nematodes. In an attempt to identify parasite antigens that elicit such 'protective' host responses, we compared the antigen recognition patterns of persons who remained amicrofilaraemic after 3-6 years of exposure to Brugia malayi with those of individuals who developed patent filariasis during the same period. IgG antibodies in sera from immigrants identified between 0 and 25 microfilarial antigens on Western blots. The highest degree of reactivity was observed with antigens in the 65-75 kD and 20-30 kD ranges, and with a group of high mol. wt antigens (greater than 180 kD). Sera from amicrofilaraemic donors preferentially reacted with 70/75 kD microfilarial antigens. A proportion of such sera inhibited the binding of monoclonal antibody MF1 to its target epitope; eight of nine inhibitory sera were from patients with active infections, evidenced by the presence of microfilariae or filarial antigens in the donors' blood, but who were amicrofilaraemic. These results indicate that some amicrofilaraemic residents of areas where brugian filariasis is endemic develop immune reactions to a microfilarial stage-specific antigen that was previously identified as a potentially 'protective' parasite antigen in animal models of lymphatic filariasis. PMID- 2320382 TI - Injection of microfilariae induces resistance to Brugia malayi infection in ferrets and accelerates development of lymphostatic disease. AB - Ferrets injected intravenously with living microfilariae or cutaneously with microfilariae followed by intravenous injection developed partial resistance to a challenge infection as measured by recovery of adult filariae from lymphatics. Following a challenge infection, the ferrets injected with microfilariae developed lymphatic pathology characteristic of a chronic infection or that observed following multiple infections. There was disruption of lymphatic drainage of the infected limb and lymphoedema. The results suggest that immune responses to antigens of microfilariae, presumably antigens shared with other developmental stages, effected both increased resistance and enhanced lymphatic pathology. PMID- 2320383 TI - Early appearance of variant parasites in Plasmodium chabaudi infections. AB - Previous studies have shown that the recrudescence parasitaemias seen in mice infected with Plasmodium chabaudi AS strain are antigenically different from the infecting parent population. Antigenic differences between recrudescent and parent populations were demonstrated in a passive transfer assay. In the present study, using the same assay system, it has been shown that in some mice, variant parasites (i.e. different from the parent population) can be detected at a time when the primary parasitaemia is still patent but in remission. This is the first report in Plasmodium of variant parasites being detected during the course of a patent primary parasitaemic episode of an infection initiated with a cloned line. PMID- 2320384 TI - Pediatric update #11. Congenital radioulnar synostosis. A new technique for derotational osteotomy. AB - Hyperpronation deformity due to congenital radioulnar synostosis has previously been managed by derotational osteotomy through the synostosis, while stabilization has been achieved with K-wires and a long arm cast. The technique presented here uses a small external fixation device that allows precise rotational correction and affords adequate stabilization yet avoids cast immobilization. PMID- 2320385 TI - Tips of the trade #21. Simplified starting technique for femoral intramedullary rodding. AB - A simplified method for determining the position of and creating the proximal starting hole for a femoral intramedullary rod is presented. The method, which uses the combination reamer from the DHS hip screw set and other equipment found in most operating rooms, increases the certainty of correct placement of the proximal starting hole. The difficulties and risks inherent in the use of the starting awl are eliminated. PMID- 2320386 TI - A pediatrician's view. PMID- 2320387 TI - Morphology and filterability of red blood cells in neonatal and adult rats. AB - Red blood cell (RBC) deformability in rats of various ages was assessed by filtration (3 micron Nucleopore membranes). Neonatal rat RBC (1 d old) had lower filterability, both in terms of RBC incremental volume (9.97 +/- 1.85 versus 0.33 +/- 0.28 nL at 180 d of age, mean +/- SD, p less than 0.001) and the number of filter clogging particles (25.7 +/- 3.1 versus 18.9 +/- 3.4 RBC x 10(3)/s, p less than 0.001). The lower filterability correlated with a larger RBC volume (169 +/- 12.6 versus 69 +/- 3.2 microns 3, p less than 0.001) and with a wider minimum cylindrical diameter (3.87 +/- 0.15 versus 2.84 +/- 0.05 microns, p less than 0.001). Almost all of the neonatal RBC had a minimum cylindrical diameter exceeding the 3 microns nominal pore size of the filters. The calculated resistance to initial folding was also significantly greater, as indicated by a static bending analysis of initial deformation. However, when the larger size of neonatal RBC was taken into consideration, and thus their greater projected area on which forces are applied, they appear to be at least as deformable as the adult type RBC. This finding may explain the contradiction between RBC filtration experiments and other approaches based on RBC deformations in shear flow, which have been unable to detect a hampered flexibility of neonatal RBC. In view of the more pronounced differences between neonatal and adult RBC in rats than in human subjects, the rat is an interesting model for studying this physiologic phenomenon in newborns. PMID- 2320388 TI - The capability of neonatal leukocytes to produce IL-6 on stimulation assessed by whole blood culture. AB - IL-6 is a cytokine with a wide variety of influences on the cells involved in immune and inflammatory responses. Defective production of IL-6 may be partly responsible for the impaired immune defense and inflammatory response often observed in the neonatal period. In our study, we used whole blood culture to examine the capacity of neonatal leukocytes to produce IL-6 in response to various stimuli. IL-6 activity was evaluated by growth promoting assay using an IL-6-dependent murine hybridoma clone. IL-6 activity was undetectable in fresh or unstimulated blood obtained from both newborns and adults. In contrast, incubation of whole blood with lipopolysaccharide or concanavalin A resulted in marked IL-6 activity. After stimulation, IL-6 activity was induced as early as 2 h after culture and increased with time, reaching a plateau at around 12 h. Comparative examinations suggested that the IL-6 activity induced in neonatal blood on stimulation was similar to that seen in stimulated adult blood. Neutralization experiments with anti-IL-6 anti-serum confirmed the presence of IL 6 proteins in the stimulated blood, and induction of cellular IL-6 mRNA was demonstrated in the stimulated blood as well. In addition, immunocytochemical observations suggested that the major IL-6 producing cells in the stimulated blood may be monocytes. The results suggest that the production of IL-6 in response to specified stimuli is normal at birth. PMID- 2320389 TI - Identification of the heterozygotes for deficiency of the beta-subunit of the eighth component of complement by reduced levels of C8 beta and increased amounts of free C8 alpha-gamma. AB - Sera from obligate heterozygotes for deficiency of the C8 beta subunit of the eighth component of human complement (C8) were analyzed for the molecular composition of C8. The C8 alpha-gamma and C8 beta subunits were separated by SDS PAGE, visualized by immunoblotting, and the resulting bands were quantitated by laser densitometry. The laser densitometric absorption data were set to 100 arbitrary units (AU) for both subunits of pooled normal human sera. The AU values of individual normal sera ranged from 45 to 150 AU for C8 alpha-gamma (median 99 AU) and from 45 to 140 AU for C8 beta (median 101), whereas the C8 alpha-gamma/C8 beta-ratio varied from 0.7 to 1.4. Sera from C8 beta-deficient heterozygotes differed, as expected, from the normal sera for the markedly reduced levels of C8 beta (20 to 90 AU, median 55 AU) and for the higher C8 alpha-gamma/C8 beta-ratio (1.3 to 3.5). High voltage agarose gel electrophoresis was used to separate free and C8 beta-bound C8 alpha-gamma. The migration of free and C8 beta-bound C8 alpha-gamma subunit was checked by hemolytic overlay gels and by second dimension SDS-PAGE and immunoblotting. Immunochemical evaluation of C8 alpha-gamma using this system revealed about 5-14% free C8 alpha-gamma in sera with normal C8 and higher levels, from 33-71%, in the C8 beta D heterozygous sera. Functional analysis confirmed the substantial increase of free C8 alpha-gamma in the heterozygous group. We conclude that the C8 in C8 beta D heterozygous sera is characterized by increased amounts of free C8 alpha-gamma due to reduced concentrations of the C8 beta subunit. This finding may help to identify individuals heterozygous for C8 beta deficiency. PMID- 2320390 TI - The distribution of T and B lymphocyte populations and MHC class II expression in human fetal and postnatal intestine. AB - The development of the intestinal mucosal immune barrier is an important protective adaptation for postnatal life. The distribution and phenotype of T and B lymphocytes in human fetal intestine and lymphoid tissues have been characterized and compared to the distribution and phenotype of lymphocytes in postnatal intestine. The characterization of lymphocyte phenotype and MHC class II antigen distribution was done using MAb and an avidin-biotin complex immunohistochemical staining technique. Intraepithelial lymphocytes were occasionally present in fetal intestine and were primarily CD3+, CD8+. T lymphocytes were readily identified in the lamina propria of fetal intestine, but most were clustered in lymphoid aggregates. Cells identified by anti-IgA1 and anti-IgA2 were the most numerous cells of B cell lineage in the lamina propria of postnatal intestine, whereas IgM+ and IgD+ lymphocytes predominated in fetal tissues. However, IgA-bearing cells were identified in lymphoid aggregates of the intestine or spleen of some fetuses. This finding suggests that B lymphocytes can undergo Ig switching in utero. Additionally, fetal intestinal epithelial cells did not express MHC class II antigens, unlike some postnatal intestinal tissues. It is possible that postnatal events such as antigen exposure may be important for the induction of these class II antigens on intestinal epithelial cells. PMID- 2320391 TI - Molecular forms of lactoferrin in stool and urine from infants fed human milk. AB - The molecular forms of lactoferrin (LF) were examined in stools and urine collected at 2.5 or 5 wk of age from very low birth wt infants fed either a cow's milk formula or a fortified human milk preparation. LF was not found by Western blotting in excreta from infants fed cow's milk. In contrast, intact and fragmented forms of LF were detected in stools and concentrated urine of each infant who received human milk. Only intact LF was detected in the fortified human milk preparation, whereas many types of LF fragments were present in the stools and urine. The approximate molecular wt of the most prominent fragments were 44, 38, 34, and 32 kD. However, the stools also displayed lower molecular wt fragments that were not found in urines of those infants. The LF fragments in those excreta were similar in size to those produced in vitro by limited digestion of apo-LF with trypsin. Furthermore, fragments produced by in vitro proteolysis were immunoreactive in an ELISA for LF. Thus, the fragments of LF in stools of very low birth wt infants fed human milk appeared to be produced by in vivo proteolysis, and the close resemblance between the LF fragments in the stools and urine suggests that the urinary LF fragments originated in the gastrointestinal tract. It remains unclear, however, whether the whole LF molecules that were fragmented were derived solely from ingested LF in human milk or in part from LF produced by the infant in response to human milk feedings. PMID- 2320392 TI - Evaporative cooling as an adjunct to ice bag use after resuscitation from heat induced arrest in a primate model. AB - Heat stroke and other hyperthermia-related crises are serious clinical problems in childhood and adolescence. Rapid cooling is required to reduce morbidity and mortality. A variety of effective cooling methods exist, and some may interfere with monitoring and resuscitation or are not readily available. We studied in 12 pigtail monkeys the pathophysiology of immersion hyperthermia (42 degrees C) to cardiac arrest (1 min no flow) and CPR plus cooling to normothermia for restoration and stabilization of spontaneous normotension. This was followed by intractable shock and secondary arrest. These studies gave us the opportunity to compare two simple cooling methods applied during and after CPR: group I (n = 6) received application of ice bags to the groins, axillae, and neck. Group II (n = 6) received ice bags plus cold water wetting (sponging) over the entire anterior surface of trunk and extremities, plus fanning. CPR restored spontaneous circulation in four of six in each group, after CPR of 1.5-16 min (NS between groups). Speed of cooling correlated with speed of stabilization of spontaneous normotension. After cardiac arrest and during and after CPR, rectal temperature had declined from a lethal level of 42.2 degrees C to a safe level of 38.5 degrees C within 45 +/- 6 (38-53) min in group I, and within 28 +/- 4 (23-32) min in group II (p less than 0.05). Epidural and esophageal temperatures declined more rapidly than rectal temperature. For critical hyperthermia, we recommend immediate application of ice bags, cold water wetting (sponging), fanning, and head cooling combined when invasive blood cooling (the most effective method) is not immediately available. PMID- 2320393 TI - Rapid clearance of surfactant-associated palmitic acid from the lungs of developing and adult animals. AB - Palmitic acid is a minor component of natural surfactant and has been used to modify lipid extracts of natural surfactants to optimize their in vitro surface properties. The metabolic fate of palmitic acid in surfactant is unknown. The clearance of surfactant-associated radiolabeled palmitic acid after intratracheal administration was investigated with trace doses of surfactant in the adult rabbit and with trace and treatment doses in the 28-d fetal rabbit and the 132-d fetal sheep. Palmitic acid was cleared rapidly from the airways, with less than 2% of the radiolabel recovered as free palmitic acid in the alveolar wash by 1 h in all models. Recovery as free palmitic acid in the total lung at 2 h was 2% in the adult rabbit and 3% both doses in the preterm rabbit. In the preterm sheep, the recovery as free palmitic acid in the total lung was approximately 2% of the trace dose and 1% of the treatment dose by 5 h. Between 5 and 15% of the instilled palmitic acid was used as substrate for phospholipid synthesis by the lung in the different models. About 30% of the palmitate derived label was recovered in lipid extracts of liver 30 min after tracheal instillation of labeled surfactant in adult rabbits, whereas only 5-10% of the palmitate derived label was found in liver lipids in the preterm animals. In contrast to palmitic acid, radiolabeled triglyceride was cleared much more slowly from the airspaces and lungs of preterm sheep. Inasmuch as large amounts of palmitic acid are cleared rapidly from airspaces and lung tissue, it will not have a prolonged effect on the surface properties of surfactant but it may serve as a precursor for lung lipid metabolism. PMID- 2320394 TI - Late gestation alterations in fetal pulmonary lactate metabolism in vivo. AB - We have previously shown that lactate is produced by the ovine fetal lung. Inasmuch as factors that might affect lactate production, such as pulmonary glucose and oxygen uptake, change late in gestation we investigated whether pulmonary lactate metabolism also changes. Eleven chronically catheterized fetal lambs were studied over 119-141 d gestation. Lactate, glucose, and oxygen concentrations were measured in the pulmonary artery (PA) and vein while lung blood flow was determined using labeled microspheres. Between early studies (less than or equal to 127 d) and studies near term (greater than or equal to 134 d) PA lactate levels did not change, but due to increasing pulmonary blood flow, lung lactate delivery rose 51% (p less than 0.05). Because of a decline in PA glucose, lactate also made up a larger fraction of the major nonnitrogenous substrate in PA blood near term (p less than 0.001). Despite this, no net pulmonary uptake of lactate occurred. Lactate production continued, but decreased by 80% between early and late studies (p less than 0.05) and the maximum fraction of glucose uptake that could be accounted for by lactate production dropped from 0.78 to 0.20 (p less than 0.025). Correlations were found between lung lactate production and glucose uptake also correlated with PA glucose (p less than 0.05). No relationships were observed between lactate production and PA oxygen content, oxygen delivery, lactate concentration, or lactate delivery. The decreasing fraction of glucose uptake explained by lactate production suggests that metabolism of pulmonary glucose is altered near term. The correlation between decreasing glucose delivery and declining lactate production also suggests that glucose itself influences this change. PMID- 2320395 TI - Stroke volume and left ventricular output in preterm infants with patent ductus arteriosus. AB - To assess the effect of patent ductus arteriosus (PDA) on left ventricular output (LVO) we studied stroke volume (SV), LVO, and heart rate (HR) in 21 very low birth wt preterm neonates with clinically symptomatic PDA before and after surgical ligation. Six additional infants were also studied before PDA with left to-right shunt was detectable by the pulsed Doppler technique. Gestational age (median and range) was 28 (24-32) wk. SV was measured by duplex Doppler and M mode echocardiography, and LVO was calculated as product of SV and HR. LVO was 419 (305-562) mL/min/kg during symptomatic PDA. It decreased to 246 (191-292) mL/min/kg after ligation (n = 21, p less than 0.001). SV was 2.69 (1.98-4.10) mL/kg during symptomatic PDA decreasing to 1.63 (1.22-1.98) mL/kg after ductal closure (n = 21, p less than 0.001). HR did not change after ductal closure. In the six infants with three examinations, LVO and SV were normal before detectable ductal left-to-right shunt and after ligation, but LVO was increased by 59.5 +/- 23% (mean +/- SD) (p less than 0.05), and SV by 60 +/- 32% (p less than 0.05) during symptomatic PDA. In conclusion, preterm neonates with RDS, requiring mechanical ventilation, increased LVO during symptomatic PDA by increasing their SV, and not by changing their HR. PMID- 2320396 TI - Fetal uptake of intraamniotic digoxin in sheep. AB - To explore the possibility that intraamniotic administration of digoxin is an effective treatment regimen for fetal tachyarrhythmia, we injected digoxin into the amniotic fluid cavity of pregnant sheep and examined the time course of digoxin distribution to the fetal and maternal plasma compartments. Animals were studied in two groups according to digoxin dosage: 0.7-1.8 nmol/kg fetal body wt in the high-dose group (n = 6) and 0.1-0.6 nmol/kg fetal body wt in the low-dose group (n = 14). Within 1 h, plasma digoxin concentrations in the high-dose and low-dose groups were 18.2 +/- 15.0 nmol/L and 2.7 +/- 0.8 nmol/L, respectively (values are expressed as mean +/- SD). At 6 h digoxin concentrations were 13.8 +/ 7.0 and 3.1 +/- 0.9 nmol/L, and at 24 h they were 2.3 nmol/L (n = 1) and 1.8 +/- 1.2 nmol/L, respectively. Peak maternal digoxin levels were about one-tenth fetal values in the high-dose group and undetectable in the low-dose group. Fetal digoxin concentrations were significantly greater in the descending aorta than in the umbilical vein (p less than 0.02). Fetal arterial blood pressure and heart rate were not significantly different from control at any time after digoxin administration. These results demonstrate that digoxin is rapidly taken up into the fetal circulation from the maternal amniotic cavity. The exact mechanism whereby this occurs is unknown, but transplacental transfer from the maternal circulation is not involved. Our findings suggest that intraamniotic administration of digoxin may be an alternative treatment for fetal tachyarrhythmias when direct administration of antiarrhythmic agents is ineffective or produces maternal toxicity. PMID- 2320397 TI - Xanthine oxidase during human fetal development. AB - Through oxygen free-radical production, xanthine oxidase (XOD, E.C.1.2.3.2) has been implicated in the pathogenesis of postischemic and hyperoxic tissue injuries among newborn. We measured the activity and evaluated the kinetic characteristics of XOD in human fetal liver, intestine, brain, and myocardium. Both the fetal liver and intestine contain a high XOD activity through gestation. The activity increases in the liver and decreases in the intestine with advancing gestation. The apparent Km for hypoxanthine is 4.8-5.5 microM in the intestine throughout gestation and in the liver at term but higher than 30 microM in the liver during the first half of pregnancy. The activity is undetectable both in the fetal brain and myocardium throughout gestation. Thus, XOD activity is present at least in the liver and intestine to account for the oxidation of hypoxanthine and xanthine. However, direct evidence for adenine nucleotide catabolism, followed by oxidation of the accumulated hypoxanthine during tissue reoxygenation in the human liver or intestine is not available. PMID- 2320398 TI - Spectral edge frequency as a simple quantitative measure of the maturation of electrocortical activity. AB - The feasibility of using spectral edge frequency (SEF) as a single quantitative measure of the maturation of electrocortical activity is demonstrated in a large number of fetal lambs studied throughout the 3rd trimester. A total of 43 electrocortical recordings obtained from 23 fetal lambs ranging from 116-140 d were subjected to power spectral analysis using the fast Fourier transform. Spectral edge frequency was calculated as the frequency below which 90% of the power resides. The SEF was found to be highly sensitive in identifying the transition between high-voltage slow-activity and low-voltage fast-activity electrocortical activity. By 125 d, the distribution of SEF clearly showed two distinct populations, a low SEF with peak values ranging from 3-9 Hz; and a high SEF (SEFH) with values ranging from 13-23 Hz. Increase in gestational age was associated with a progressive increase in SEFH, which can be described by the linear function (SEF = 0.53GA-51.3). This progressive increase in SEFH reflects the gradual acquisition of faster frequencies. In contrast, low SEF declined with age before 130 d, but then stabilized at 4 Hz throughout the rest of gestation. As a result, there was a gradual increase in the separation between SEFH and low SEF as a function of gestational age. PMID- 2320399 TI - Glutaric acidemia type II: heterogeneity of clinical and biochemical phenotypes. AB - We have examined 23 fibroblast lines from patients with neonatal and late onset glutaric acidemia type II and fibroblasts from four parents of these patients. Fifteen of these patients are previously unreported. Results of these investigations show deficiency of electron transfer flavoprotein or electron transfer flavoprotein-ubiquinone oxidoreductase activity in all of the patients' fibroblasts. Immunoblots indicate that the steady state levels of the antigens is very low or undetectable in most of the neonatal onset patients; however, cross reacting antigen without electron transfer activity is observed in several glutaric acidemia type II fibroblast lines. Assay of parental lines confirm the autosomal transmission of deficiencies of proteins. Of particular interest is the clinical heterogeneity among these patients. Patients may present with an extrapyramidal movement disorder as observed in glutaric aciduria type I, without the typical organic aciduria typical of glutaric acidemia type II even in the presence of severe enzyme deficiency, or with renal cystic dysplasia accompanying electron transfer flavoprotein deficiency. Renal cystic dysplasia had previously been reported only in patients with electron transfer flavoprotein-ubiquinone oxidoreductase deficiency. PMID- 2320400 TI - The American Pediatric Society and the Society for Pediatric Research. Abstracts and program outline. Anaheim, CA, May 7-10, 1990. PMID- 2320401 TI - Deutsche Physiologische Gesellschaft. Abstracts of the 68th meeting (spring meeting). 6-9 March 1990, Heidelberg. PMID- 2320402 TI - [Biostimulation with low-intensity lasers--physics or metaphysics?]. AB - The use of low-intensity lasers for biostimulation continues to produce controversies. This paper presents the basic principles of light propagation in tissue. Tissue properties such as fluorescence, absorption and scattering initiate a gradual loss of any "laser-specific" property of the light with distance from the irradiated surface. One of the aims of the discussion is to indicate if a given biological response is expected to be specifically dependent on a laser source, or if the same result also ought to be expected from more conventional light sources. PMID- 2320403 TI - [Hereditary cerebral hemorrhage. Dementia with cystatin C amyloidosis]. AB - Nineteen cases of hereditary cystatin C amyloidosis with cerebral haemorrhage are described. The first haemorrhage occurred between the ages of 20 and 41 years and the period of survival varied from 10 days to 23 years after the first insult. Progressive dementia was a striking clinical symptom in 17 of the patients and in two cases dementia was the first sign. At the last examination severe dementia and pronounced pathological EEG were established in the majority of the patients. Infiltration of amyloid substance positive for anti-cystatin C was found in the proximity of the blood vessels and in their walls. Lesions in the cerebral microvascular system together with haemorrhages and infarcts caused thereby were considered to be an adequate explanation of the dementia in these patients. In view of the discovery of amyloid discharges in tissues outside the CNS it is adjudged more correct to use the name Hereditary Cystatin C Amyloidosis (HCCA). PMID- 2320404 TI - [Automobile driving--in shock and greatly stressed]. PMID- 2320405 TI - [Etiology and prevention of disease--theory and practice]. AB - The prevention of diseases requires that their causes are known. The article presents central epidemiological concepts which relate to causality and demonstration of causal connections. It refers these to prophylactic medicine and to the future assignment of priorities as regards research funds. PMID- 2320406 TI - [The clinician as author and researcher--problems experienced by young doctors]. PMID- 2320407 TI - The abortion issue in the US. PMID- 2320408 TI - [Treatment, care and prevention for HIV-positive intravenous drug addicts]. PMID- 2320409 TI - Hoffman finds pediatrics both intense and rewarding. Interview by Jan Thornburg. PMID- 2320410 TI - Synthesis and characterization of a ribavirin-3',5'-phosphate pentadecamer homoribopolymer bearing a 5'-amino tether group and a 3'-thymidine. AB - The synthesis of a pentadecamer of the 5'-phosphate of the antiviral nucleoside ribavirin (1'-beta-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) has been achieved. This homoribopolymer is terminated at the 5'-position with an (6 aminohexyl)phosphate group to permit conjugation to a carrier and at the 3' position by a thymidine-5'-phosphate. The synthesis was accomplished using the methyl phosphoramidite approach to oligoribonucleotides. The homoribopolymer was insensitive to ribonuclease A but was sensitive to ribonuclease T2 digestion. PMID- 2320411 TI - Modelling of the binding specificity in the interactions of cationic porphyrins with DNA. AB - A theoretical investigation is performed of the complexes of a tetracationic porphyrin, tetra-(4-N-methylpyridyl)-porphyrin, (T4MPyP), with the hexanucleotides d(CGCGCG)2 and d(TATATA)2, considering the possibility of both the intercalative and the groove binding interactions. These computations demonstrate that T4MPyP manifests a significant preference for intercalation in its complex with d(CGCGCG)2 but for non intercalative binding in the minor groove in its complex with d(TATATA)2. Such a dual binding behaviour of T4MPyP as a function of the sequence to which it is attached is fully consistent with available experimental data. It demonstrates that intercalation and groove binding may be viewed as two potential wells on a continuous energy surface. In agreement with experiment, the computations indicate that in the here considered case the deepest well is associated with intercalation. PMID- 2320412 TI - Post-transcriptional control of c-myc proto-oncogene expression by glucocorticoid hormones in human T lymphoblastic leukemic cells. AB - We have studied the regulation of the human c-myc proto-oncogene by glucocorticoid hormones in T lymphoblastic leukemic cells. A significant decrease (50%) of the steady state levels of c-myc mRNA was observed as early as 3 h after dexamethasone treatment of CEM-1.3 human lymphoma cells, reaching less than 5% values, with respect to untreated cells, 24 h after hormone administration. Nuclear run-on experiments showed no modifications of the transcriptional rate from the first exon. However, a slight decrease (15%) of the transcript elongation from the first exon/first intron boundary was observed in the dexamethasone-treated cells. Using actinomycin D to block gene transcription, we have observed a significant increase in the rate of c-myc RNA specific decay after dexamethasone treatment. Furthermore, cycloheximide was able to overcome completely the dexamethasone-induced down-regulation of the c-myc gene expression. Our data suggest that dexamethasone is able to inhibit human c-myc gene expression primarily at the post-transcriptional level, through the synthesis of hormone-induced regulatory protein(s) controlling c-myc transcript stability. PMID- 2320413 TI - The tymobox, a sequence shared by most tymoviruses: its use in molecular studies of tymoviruses. AB - The 5'-terminal sequences of the virion protein mRNAs of ononis yellow mosaic and kennedya yellow mosaic tymoviruses were determined, and also the positions in the genomes of the transcription initiation sites of those mRNAs. Comparisons of the available genomic sequences of tymoviruses revealed two conserved regions, one at the initiation site and another longer sequence of sixteen nucleotides to the 5' side of it. The longer sequence, which we call the tymobox, was tested as a target for a designed ribozyme, which cleaved appropriate genomic fragments of three tymoviruses. A synthetic oligonucleotide with sequence complementary to the tymobox was shown to be a tymovirus-specific probe for diagnosing and identifying tymoviruses, except for wild cucumber mosaic tymovirus. The tymobox sequence was also used as a primer for the second strand DNA synthesis of dsDNA representing the virion protein gene of cacao yellow mosaic tymovirus, a tymovirus with unknown sequence. Thus, the tymobox is a useful tool in molecular studies of tymoviruses. PMID- 2320414 TI - Tissue- and species-specific promoter elements of rat gamma-crystallin genes. AB - The 5' flanking regions of the six rat gamma-crystallin genes (gamma A-gamma F) are all capable of conferring lens-specific expression to the bacterial chloramphenicol acetyl transferase (CAT) reporter gene in either transdifferentiating chicken neural retina cells or mouse lens epithelial cells. Deletion mapping of the most active gamma-crystallin promoter region, the gamma D region, showed that at least three elements are required for maximal expression in mouse lens epithelial cells: element(s) located between -200 and -106, a conserved CG rich region around position -75, and a CG stretch around -15. The region between -200 and -106 was dispensable in transdifferentiating chicken neural retina cells, which instead required the region between -106 and -78. The maximal activity of the gamma E and gamma F promoters was also dependent upon the integrity of the conserved CG region located around -75. A synthetic oligonucleotide containing this sequence was capable of lens-specific enhancement of the activity of the tk promoter in transdifferentiating chicken neural retina cells but not in mouse lens epithelial cells. Our results further show that this region may contain a silencer element, active in non-lens tissues, as well. PMID- 2320415 TI - Elongation and maturation of c-myc RNA is inhibited by differentiation inducing agents in HL60 cells. AB - Maturation of c-myc mRNA proceeds in a given order in HL60 cells. It starts with splicing of intron 2, continues with splicing of intron 1 and ends with 3' cleavage and polyadenylation of the primary transcript. This process is inhibited, when HL60 cells were induced to terminal differentiation by dimethylsulfoxide (DMSO). DMSO interferes specifically with maturation of c-myc but not c-abl RNA in HL60 cells. Simultaneously, DMSO induces a block to RNA elongation at the boundary of c-myc exon 1 and intron 1 in HL60 cells. Participation of the same factor(s) in the regulation of c-myc RNA elongation and splicing is supposed. PMID- 2320416 TI - Transcription factor USF from duck erythrocytes transactivates expression of the histone H5 gene in vitro by interacting with an intragenic sequence. AB - The duck histone H5 gene contains a 12 base pair (bp) sequence motif within the coding region, which shows homology in 10 out of 12 bp with the consensus sequence of the USF binding site in the Ad2ML-promoter. The functional equivalent of transcription factor USF, partially purified from whole cell extracts of duck erythrocytes (EUSF), was shown to interact with this intragenic sequence. Electrophoretic mobility shift analyses revealed the selective formation of a complex between this protein fraction and the duck H5 gene. Footprint assays with DNase I delineated specific binding to the intragenic sequence outlined above. Moreover this protein fraction, containing EUSF, transactivates the expression of the duck H5 gene in vitro and elimination of the USF-consensus sequence leads to a loss of stimulation but retains the basic transcription of the gene. These results suggest an as yet unknown functional role of EUSF in the expression of the H5 gene of the duck. PMID- 2320419 TI - Nucleotide sequence of the genes encoding the L11, L1, L10 and L12 equivalent ribosomal proteins from the archaebacterium Halobacterium marismortui. PMID- 2320417 TI - The lack of protamine 2 (P2) in boar and bull spermatozoa is due to mutations within the P2 gene. AB - The nuclei of spermatozoa in all mammals examined so far contain P1 protamine. A second protamine variant, protamine P2, has to date been isolated only from human and murine spermatozoa where it represents the major fraction of basic nuclear protein. In order to elucidate the reason for this unusual distribution of the protamine variants among mammals we have investigated the expression of protamine P2 in boar and bull. It can be shown that also in these species protamine 2 is transcribed and translated on low levels. Various mutational events though have altered the primary structure of the protein: In boar, a deletion of 8 aminoacids has removed a sequence motif from the amino-terminus of the molecule, which highly probable is of functional relevance. The bovine sequence, as a consequence of numerous point mutations has accumulated neutral and hydrophobic aminoacids which reduce the affinity of the protamine 2 to DNA. PMID- 2320418 TI - Molecular mechanics of the interactions of spermine with DNA: DNA bending as a result of ligand binding. AB - We used energy minimization of a molecular mechanical force field to evaluate spermine interactions with B-form DNA oligomers with either alternating purine/pyrimidine or homopolymeric sequences. Four different positions for spermine docking--within, along, and bridging the minor groove and bridging the major groove--were assessed for each sequence. Interaction at the major groove of alternating purine/pyrimidine sequences appears to be the most favorable of all models assessed, and are associated with significant bending of DNA. Interactions at the major groove of homopolymers were less favorable than those of heteropolymers and showed little or no bending. Interactions with the minor groove were most favorable for spermine positioned near the base of the groove, and became less favorable as spermine was moved toward the top of the groove. Association along the phosphate backbone alone was the least favorable of the interactions. PMID- 2320420 TI - cDNA sequences of chicken nucleolin/C23 and NO38/B23, two major nucleolar proteins. PMID- 2320421 TI - Nucleotide sequence of the intergenic spacer and the 18S ribosomal RNA gene from mustard (Sinapis alba). PMID- 2320422 TI - The primary structure of human cartilage link protein. PMID- 2320423 TI - Complete nucleotide sequence of the genome of Spiroplasma citri virus SpV1-R8A2 B. PMID- 2320424 TI - The 5' end of the coding region of a U6 RNA gene candidate from tomato starts with GUCC, a phylogenetically highly conserved 5' end sequence of U6 RNA. PMID- 2320425 TI - Sequence of the trnH gene and the inverted repeat structure deletion site of the broad bean chloroplast genome. PMID- 2320426 TI - Primary structure of mouse chromogranin B deduced from cDNA sequence. PMID- 2320427 TI - Nucleotide sequence of the 3'-terminal region of artichoke mottled crinkle tombusvirus RNA. PMID- 2320428 TI - Nucleotide sequence of a putative transcription factor recognizing the thyroglobulin promoter. PMID- 2320429 TI - Nucleotide sequence of the bovine enteric coronavirus BECV F15 mRNA 5 and mRNA 6 unique regions. PMID- 2320430 TI - Sequence of a murine cDNA, pcp-4, that encodes the homolog of the rat brain specific antigen PEP-19. PMID- 2320431 TI - Nucleotide sequence of a coleopteran-active toxin gene from a new isolate of Bacillus thuringiensis subsp. tolworthi. PMID- 2320432 TI - Improvement of PCR amplified DNA sequencing with the aid of detergents. PMID- 2320433 TI - Haemophilia B caused by mutation of a potential thrombin cleavage site in factor IX. PMID- 2320434 TI - An STS in the human IL7 gene located at 8q12-13. PMID- 2320436 TI - Nucleotide sequence of the coat protein gene and flanking regions of cucumber virus (CMV) strain 117F. PMID- 2320437 TI - [The risk of recurrence following the thyrostatic treatment of immunogenic and nonimmunogenic hyperthyroidism]. AB - Data of 196 patients treated for hyperthyroidism exclusively with antithyroid drugs were analyzed retrospectively concerning the relapse rate within a follow up period of four years. Patients were subdivided for primary or recurrent disease, and for immunogenic or non-immunogenic hyperthyroidism, respectively. In immunogenic as well as in non-immunogenic hyperthyroidism, the relapse rate was significantly lower for patients with primary disease (35% and 52%, respectively) compared to those with recurrent hyperthyroidism (82%, p less than 0.001 and 83%, p less than 0.001, respectively). In patients with primary disease, clinical, biochemical and scintigraphic parameters were tested with respect to their capability of predicting a relapse. For immunogenic hyperthyroidism the highest relapse rates were observed in young patients and in those with large goitres, whereas for non-immunogenic hyperthyroidism they were highest in old patients, in those with nodular goitres and in those without an increased urinary iodine excretion at the time of diagnosing hyperthyroidism. PMID- 2320438 TI - The fate of 131I-17-iodoheptadecanoic acid during lactate loading: its oxidation is strongly inhibited in favor of its esterification. A radiochemical study in the canine heart. AB - The influence of lactate loading on fatty acid metabolism (pH = 7.4) by the normal canine heart was investigated radiochemically using the radioiodinated fatty acid 131I-17-iodoheptadecanoic acid (131I-17-HDA). Fatty acid metabolism was studied during control conditions (n = 8) and after lactate loading (n = 7). In the canine heart total myocardial 131I-17-HDA radioactivity (uptake) was not changed during the lactate intervention. The oxidation decreased fivefold (measured as free 131I-iodide ion) from 70% to 14% (p less than 0.0001, Student's t-test). Thin-layer chromatography of cardiac lipids demonstrated that the non oxidized 131I-17-HDA was mainly stored in the triglycerides and phosphoglycerides. These results suggest that lactate inhibits cardiac 131I-HDA oxidation. PMID- 2320435 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2320439 TI - The influence of lactate and dipyridamole on myocardial fatty acid metabolism in man, traced with 123I-17-iodoheptadecanoic acid. AB - Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123I-17 iodoheptadecanoic acid (123I-17-HDA). In patients (paired, n = 7) lactate loading decreased the uptake of 123I-17-HDA significantly from 27 (control: 22-36) to 20 counts/min/pixel (16-31; p less than 0.05 Wilcoxon). The half-time value increased to more than 60 min (n = 5), oxidation decreased from 61 to 42%. Coronary vasodilatation, a well-known side effect of lactate loading, was studied separately in a dipyridamole study (paired, n = 6). Coronary vasodilatation did not influence the parameters of the time-activity curve. These results suggest that changes in plasma lactate level as occurring, among other effects, during exercise will influence the parameters of dynamic 123I-17-HDA scintigraphy of the heart. PMID- 2320441 TI - Under siege. PMID- 2320440 TI - [Determination of cerebral blood flow using an 81Rb/81mKr generator system]. AB - A method is being developed which not only measures cerebral blood flow as a static quantity but also its changes with time. For that purpose a semiconductor device ascertains the proportion of intracerebral 81 Rb and 81mKr activities. By opening the hemato-encephalic barrier in animal experiments a sufficient concentration of intracerebral 81 Rb could be attained and the modified blood circulation after step-wise ligature of all brain arteries brought into relation to the corresponding Rb/Kr quotient. Over the range from undisturbed to completely interrupted cerebral blood flow this quotient varied up to 25% of its initial value. PMID- 2320443 TI - Pole-axed by poll tax. PMID- 2320442 TI - Greenwich in crisis. PMID- 2320444 TI - Fathering fears. PMID- 2320445 TI - Sinking profile? PMID- 2320446 TI - Post-registration education. A little more PREPP. PMID- 2320448 TI - Post-registration education. Roadshow reactions. PMID- 2320447 TI - Post-registration education could do better. PMID- 2320449 TI - Essentials of management. Communicating the basics. PMID- 2320450 TI - Making time to talk. PMID- 2320451 TI - Mental health. Blaming society. PMID- 2320452 TI - Appealing anomalies. PMID- 2320453 TI - A survivor against the odds. PMID- 2320454 TI - Health and safety. A job worth doing. PMID- 2320455 TI - AIDS--students' views. PMID- 2320456 TI - Bacteria, biofilms and bladder catheters. PMID- 2320457 TI - Setting standards. Protecting privacy. PMID- 2320458 TI - 'Haven't you finished it yet?'. PMID- 2320459 TI - The journal of infection control nursing. Ritual and risk. PMID- 2320460 TI - The journal of infection control nursing. Preaching safe practice. PMID- 2320461 TI - The journal of infection control nursing. Waste line. PMID- 2320462 TI - Resulting fears. PMID- 2320463 TI - Delivering health. PMID- 2320464 TI - Time to listen. PMID- 2320465 TI - Called to account. PMID- 2320466 TI - Forward for backs. PMID- 2320467 TI - The price of progress. PMID- 2320468 TI - Setting standards. Quality of care. PMID- 2320469 TI - Practical standards. PMID- 2320470 TI - Quality assurance makes sense. PMID- 2320471 TI - A little local difficulty? PMID- 2320472 TI - Ophthalmic triage. PMID- 2320473 TI - When is a specialist not a specialist? PMID- 2320474 TI - Dying at home. PMID- 2320475 TI - Shock story. PMID- 2320476 TI - AIDS. The New York experience. PMID- 2320477 TI - Act of humanity. PMID- 2320478 TI - Unpopular psychiatric patients. PMID- 2320479 TI - 'Don't boycott AIDS conference,' nurses told. PMID- 2320480 TI - Pediatric critical care transport survey: team composition and training, mobilization time, and mode of transportation. AB - A survey was conducted to determine the current standard of care with regard to team composition and training, mobilization time, and vehicle use for pediatric critical care transport. An evaluation of 30 pediatric referral centers revealed that 60% provide a critical care transport team. Of those teams, the mean number of transports per year was 304. Response time ranged from 10 to 90 minutes. All teams included a physician all or most of the time; 100% of teams included a critical care nurse, and 50% always included a respiratory therapist. Ambulances alone are used in 28% of systems, with the remainder using combinations of ambulances, helicopters, and fixed wing aircraft. A proposal is presented for future standards in pediatric critical care transport with regard to the factors discussed. PMID- 2320481 TI - Hypokalemia complicating emergency fluid resuscitation in children. AB - Our clinical observations suggested that vigorous fluid therapy in children often resulted in hypokalemia. A retrospective review was conducted of four years of admissions to a pediatric intensive care unit. A total of 29 patients were identified who received at least 20 ml/kg of intravenous fluid in their first hour of care and had a pretreatment and posthydration serum K obtained. The potassium levels dropped from a mean pretreatment value of 4.6 +/- 1.0 mEq/L to a mean of 3.3 +/- 0.8 mEq/L (P less than 0.005). Coincidental arterial pH measurements were available in 16 cases. A separate analysis of potassium change in this group revealed that pH change alone could not account for the drop in serum K. Significant hypokalemia may occur after aggressive rehydration of critically ill pediatric patients. PMID- 2320482 TI - Occult carbon monoxide poisoning in an infant. AB - The diagnosis of occult carbon monoxide poisoning in children is a difficult problem and may be frequently overlooked. An infant with recurrent episodes of unrecognized CO exposure and subsequent neurologic deterioration is presented. A clue to the diagnosis in this case was the finding of basal ganglia abnormalities on computed tomography. Clinical findings, etiology, and treatment of CO poisoning are reviewed. We suggest that CO toxicity should be suspected in any child with acute or recurrent neurologic deterioration. PMID- 2320483 TI - Acute toxicity from oral ingestion of crack cocaine: a report of four cases. AB - We report the symptomatology, clinical, and laboratory findings in four patients following oral ingestion of crack cocaine. All of the patients had a positive urine test for cocaine metabolites measured by gas chromatography-mass spectroscopy. Retrospective analysis of the four patients revealed alterations in function of the cardiovascular system (4), the autonomic nervous system (4), the central nervous system (3), and the gastrointestinal system (1). Three patients ingested crack cocaine as a direct result of confrontation with law enforcement officers. The symptomatologies of acute toxicity from oral ingestion of crack cocaine are related to its effect on the cardiovascular system and the brain. Cocaine toxicity should be considered in patients with acute and unexplained cardiovascular, central nervous system, or gastrointestinal complaints. Law enforcement personnel should be made aware of the signs and symptoms of cocaine intoxication and be made aware of the propensity to ingest the evidence. PMID- 2320484 TI - Interstate pedestrian crossing: a form of self-destructive behavior? AB - Emotional conflicts, malassociation with peers, and inadequate family support are not the emergency physician's primary considerations when attending a severely traumatized child. This report makes an appeal for the clinician to determine the sequence of events that preceded the trauma. Attempts should be made to distinguish between intentional and accidental trauma by viewing the event, not in isolation, but rather in the context of potential environmental stress affecting the child and family. Among the multidisciplinary coalition we forge to provide ongoing care for the trauma patient, there should be a mental health specialist. Exploration for family discord, escalating stress, and suicidal ideation should become central themes for emergency physicians who treat traumatized children. PMID- 2320485 TI - Methyldopa-induced hemolytic anemia in a 15 year old presenting as near-syncope. AB - Methyldopa is an antihypertensive medication which is available generically and under the trade name Aldomet that is widely prescribed in the adult population and infrequently used in children. Methyldopa causes an autoimmune hemolytic anemia in a small percentage of patients who take the drug. We report a case of methyldopa-induced hemolytic anemia in a 15-year-old boy who presented to the emergency department with near-syncope. The boy had been treated with intravenous methyldopa during a trauma admission seven weeks prior to presentation. Evaluation revealed a hemoglobin of three grams, 3+ Coombs' test with polyspecific anti-human globulin and monospecific IgG reagents, and a warm reacting autoantibody. Transfusion and corticosteroid therapy resulted in a complete recovery of the patient. Emergency physicians treating children must be aware of this syndrome in order to diagnose and treat it correctly. A brief review of autoimmune and drug-induced hemolytic anemias is provided. PMID- 2320486 TI - Isolated staphylococcal pericarditis following varicella in an adolescent: an unusual age-associated complication. PMID- 2320487 TI - Cat-scratch encephalopathy presenting as status epilepticus and lymphadenitis. AB - A five-year-old male was admitted to the hospital with generalized seizures. Enlarged lymph nodes raised the suspicion of cat-scratch disease. The diagnosis was confirmed by a positive history of a cat bite, typical histopathologic findings in the biopsy of the lymph nodes, and a positive skin test. Brain CT scan and LP were repeatedly normal. The clinical course was remarkable for recurrent episodes of status epilepticus refractory to usual anticonvulsant therapy and prolonged encephalopathy consisting of mental confusion, hemiparesis, tremor, chorea, and vomiting. All neurologic symptoms gradually resolved within nine months, without sequelae. Cat-scratch encephalopathy should be suspected in a child presenting with status epilepticus and enlarged lymph nodes. Aggressive and prolonged anticonvulsant therapy is strongly recommended. PMID- 2320488 TI - Walker-related burns in infants and toddlers. AB - During one year, four (6.5%) of the 61 children who were hospitalized for burns at a children's hospital sustained their injuries in a walker. Records from a total of nine children hospitalized with walker burns were compared to those from other hospitalized burned children. Patients who were burned while in a walker had a greater body surface area burned (11.6%) than those with burns from abuse (1.7%), neglect (2.5%), or other accidents (6.2%). A higher percentage of males were burned, and the burn patterns differed among all four groups. Seven of the nine walker burns resulted from scalds, with three scalds from hot grease. Walker related burn patients required more physical or occupational therapy and a longer mean hospital stay. Social histories of infants with walker and other accidental burns differed from those associated with abuse or neglect. Walkers expose infants to unnecessary hazards, including potentially serious burns; their use should be discouraged. PMID- 2320489 TI - Efficacy of sponging vs acetaminophen for reduction of fever. Sponging Study Group. AB - Seventy-three children with acute febrile illnesses were enrolled in a study to compare the efficacy of sponging, sponging plus acetaminophen, and acetaminophen alone as methods of lowering body temperature. The greatest temperature reduction was seen in the combined acetaminophen plus sponging group. The smallest temperature reduction was noted in children who received sponging alone. We urge reconsideration of routine sponging of febrile young patients. PMID- 2320490 TI - Pediatric emergency medicine on the move. PMID- 2320491 TI - Indications for chest roentgenogram in the febrile young infants. PMID- 2320492 TI - Septic shock: principles of management in the emergency department. PMID- 2320493 TI - Children with abdominal pain: evaluation in the pediatric emergency department. AB - In a retrospective study of children with abdominal pain in a pediatric emergency department, 371 children were identified during four seasonally diverse months. Half of the children were two to six years old, 32% were seven to 11 years old, and 19% were 12 to 16 years old. Forty-eight different diagnoses were made, but 10 diagnoses were given to 83% of the patients. We found an increased frequency of respiratory illnesses (12%) as compared to other studies. Appendicitis was the only surgical problem that occurred in more than one percent of the children. The diagnoses were classified as medical (64.4%), surgical (6.5%), and nonspecific (29.1%). chi 2 and multinomial logit analysis revealed that guarding and abdominal tenderness were the two symptoms which were most strongly associated with a surgical diagnosis. The goal of this work is to assist the busy emergency clinician with the difficult task of making expeditious and accurate diagnoses for children with abdominal pain. PMID- 2320494 TI - Choice of controls. PMID- 2320495 TI - Further evidence for the hypothesis that one cause of childhood leukaemia is infection. PMID- 2320497 TI - Using logistic regression in perinatal epidemiology: an introduction for clinical researchers. Part 1: Basic concepts. AB - Logistic regression is a statistical modelling technique which may be applied to estimate the simultaneous effect of a set of predictors (e.g. gestational age, birthweight) on the risk of a certain outcome variable (e.g. neonatal death) which can take either one of two possible values (yes/no, alive/dead) or in the situation where one wants to estimate the effect of a particular risk factor (e.g. sex) while adjusting (correcting) for the effect of other risk factors (e.g. gestational age). Since this situation often occurs both in medical or epidemiological research and in daily practice it is important to have a flexible and readily interpretable technique to predict risk of mortality and morbidity. Since the logistic regression technique is a powerful and widely applicable tool which is appearing more and more often in the epidemiological literature, a basic understanding of this technique becomes necessary for the clinical researcher. In this paper we explain logistic regression to medical researchers who do not have any particular statistical background. Part 1 covers the basic concepts. Part 2 will describe the actual representation of the basic concepts in a logistic framework. PMID- 2320496 TI - Preventing the sudden infant death syndrome. AB - Current efforts in the US to prevent the sudden infant death syndrome (SIDS) are largely based on pneumocardiogram screening and home apnoea monitoring. This technology does not prevent most SIDS deaths because the screening procedures lack the sensitivity and specificity needed to identify most high risk infants. In the UK the largest efforts to prevent SIDS have been based on infant health surveillance. These efforts appear to have been ineffective and along with the US failures highlight the need for new strategies to prevent SIDS. One strategy might be to develop methods to avoid known risk factors for SIDS. Prominent among these risk factors are cigarette smoking and the use of psychotropic drugs during pregnancy, overheating and infections in infants. Possible approaches to avoid these and other risks are described in the present paper. PMID- 2320498 TI - Prediction of possibly preventable death: a case-control study of postneonatal mortality in southern New Zealand. AB - The postneonatal mortality rate in three southern regions of New Zealand was 8.1 per 1000 live births for 1979-1984. The possibly preventable postneonatal mortality rate was 7.1 per 1000 live births and data on 377 possibly preventable deaths and 936 randomly selected controls were used to develop a two-stage risk scoring system. Logistic regression analysis was undertaken separately on two sub samples of the total sample. The data were used to evaluate three other previously published scoring systems. The four variables used in our birth score (mother's age, parity, marital status, and birth weight) have all appeared in other scoring systems, and this score could identify a group of infants in southern New Zealand with an estimated 1.7% mortality rate in the first year of life. It is suggested that currently the only valid use of risk-scoring in this region is for the definition of a high-risk population for the purpose of evaluating potential intervention strategies. PMID- 2320499 TI - Fumes from the spleen. PMID- 2320500 TI - Secondary enuresis in a birth cohort of New Zealand children. AB - The development of secondary enuresis was examined in a birth cohort of New Zealand children studied to the age of 10 years. By this age, 7.9% of children had developed secondary enuresis. Analysis suggested two risk factors were involved in secondary enuresis. First, children who were late to attain nocturnal bladder control had significantly higher risks of secondary enuresis than children who attained early nocturnal bladder control. Secondly, the child's level of exposure to adverse life events was associated with the onset of secondary enuresis. Children who attained bladder control after 5 years were 3.39 (1.76-6.56) times more likely to develop secondary enuresis than those who attained bladder control before the age of 3 years (P less than 0.001); children who were exposed to four or more life events in a given year were 2.56 (1.18 5.50) times more likely to develop secondary enuresis in that year (P less than 0.05). These results suggest that the rate at which the child acquires primary bladder control acts as a vulnerability factor which determines the child's susceptibility to developing secondary enuresis when exposed to stress. PMID- 2320501 TI - The social origins of Perthes' disease of the hip. AB - Four hundred and ninety-two children with Perthes' disease of the hip were identified from the records of the Family Fund which gives financial help to families of disabled children. Their social circumstances were compared with those of other children referred to the Fund. The relative risk of Perthes' disease increased with lower social class, living in a council house, parental unemployment and a larger sibship size. These findings support other evidence that the disease is caused by dietary deficiencies acting in the prenatal or early postnatal period. The Family Fund may be a useful source of information for paediatric epidemiology in Britain. PMID- 2320502 TI - The roll over test is not of value in predicting pregnancy induced hypertension. AB - As a predictor of pregnancy induced hypertension (PIH) the roll over test (ROT) has conflicting predictive values in the literature, possibly as a result of sample size, composition or methodology. In this study the roll over test was performed on 600 African women in their first pregnancy and at 26-32 weeks. The test was positive in 15% of women and had a positive predictive value of only 20%. It is concluded that the roll over test is of no value in the prediction of PIH. PMID- 2320503 TI - The Dunedin Multidisciplinary Health and Development Study: a 15 year longitudinal study. AB - This article describes the Dunedin Multidisciplinary Health and Development Study, a longitudinal study of 1037 children studied at birth and followed-up at age 3, with the majority being followed up every 2 years thereafter, to age 15. The paper includes a description of the setting for the study, the historical background, establishment of the study, the sample, follow-up rates, changes in sample characteristics over time, the procedures, the data gathered at each phase and the investigators responsible. Some of the topics studied over the years are set out in a table of descriptors which includes references to refereed journal articles that include results relating to the topics. Plans for the future are also described. Reflections on some of the reasons why the study has been successful are noted. The article concludes with a full list of publications and reports (1-328), current as at 1 July 1989. PMID- 2320504 TI - Evidence for two aspartate transport systems in prostate epithelial cells. AB - The transport of aspartate was measured in isolated prostate cells. Two kinetically distinct uptake systems of high (Km = 10.0 microM) and low (Km = 0.8 mM) affinity were observed. Transport by both systems was Na+ dependent and saturable. The tissue distribution of aspartate was also determined by measuring the washout kinetics of endogenous and radiolabeled aspartate from prostate fragments. The distribution of aspartate resulted in 47% of aspartate in the intracellular compartment and 52% in the extracellular (presumably) lumenal compartment. The distribution of aspartate resulted in a calculated intracellular to plasma concentration gradient of approximately 43. We concluded that prostate cells maintain a considerable intracellular to plasma gradient for aspartate and that these cells contain a transport mechanism capable of uptake of aspartate against this considerable gradient. PMID- 2320505 TI - Further studies on the synthesis and secretion of inhibin-like material by rat ventral prostate explants in vitro. AB - To authenticate further the testicular androgen independent status of synthesis and secretion of inhibin-like material by the rat ventral prostate, explants of this organ were maintained for a period of 6 days in vitro, altering the kind of medium used for culture. The various spent media had significant inhibin-like activity despite the absence of sera supplement in some cases. PMID- 2320506 TI - Expression of endogenous receptors for neoglycoproteins in Dunning R3327 rat prostatic carcinoma. AB - An important animal model for human prostatic adenocarcinoma is the Dunning R3327 rat carcinoma. In the present study this tumor was further characterized by analyzing the expression of endogenous sugar-binding proteins using glycohistochemistry and immunocytochemistry as well as affinity chromatography and gel electrophoresis. Our glycohistochemical and glycobiochemical results provide evidence for the presence of specific receptors for various carbohydrate moieties. Remarkably, basal cells of the Dunning tumor contain an endogenous lectin with specificity for beta-galactosides that is not found in basal cells of the normal rat prostate. This finding was corroborated using polyclonal antibodies against an immunologically related beta-galactoside-specific lectin from bovine heart. Basal cells of prostatic carcinoma may therefore behave different from normal basal cells. This difference could have a significant impact on the development of prostatic cancer. PMID- 2320507 TI - Effects of castration and androgens upon prostatic proteoglycans in rats. AB - In studies performed on male Wistar rats, castration induced atrophy of the prostate with a marked increase in the uronic acid content. The administration of testosterone propionate to castrated rats produced opposite effects. Fractionation of the glycosaminoglycans on cellulose microcolumns showed that the changes in uronic acid content in the dorsolateral lobes were due to variations in hyaluronic acid, chondroitin-4-sulfate, and dermatan sulfate, but in the ventral lobes, there were changes in all the chromatographic fractions. There were also changes in the physical properties of proteoglycans. In the ventral lobes, castration induced a wider distribution of molecular weight, increased density, and predominance of lateral chains of greater size. In the dorsolateral lobes, there was a decrease in molecular weight and density of proteoglycans and in the length of lateral chains. Opposite results were obtained when testosterone propionate was given to castrated rats. It is postulated that the effects of androgens upon prostatic growth would depend on an interrelationship between epithelium and stroma mediated by the proteoglycans. PMID- 2320508 TI - Pediatrician's perspective. Odd thoughts on well-child care. PMID- 2320509 TI - Signal-averaged electrocardiography. Promising tool for predicting sudden cardiac death. AB - Signal-averaged electrocardiography has shown great promise as an adjunct in identifying patients at risk for sudden cardiac death. Clearly, much research remains to be done. Methods and criteria must be standardized so studies can be compared and the most effective ways in which to use this technology can be determined. PMID- 2320510 TI - Sinusitis. Its association with asthma. AB - Sinusitis may present as an indolent infection, without the classic symptoms and signs commonly expected, and will probably be missed in children who have only cough and persistent rhinorrhea unless this diagnosis is kept in mind. Plain radiography is the most commonly used diagnostic procedure for sinusitis, but computed tomography may be more sensitive. The contribution of sinusitis to the induction and exacerbation of asthma is still unresolved. The existence of a nasobronchial reflex is not clearly supported by available data, although it is a likely explanation for the observed relationship between the two processes. However, sinusitis appears to be an important underlying trigger for some cases of asthma and, therefore, should be suspected any time that acute or chronic asthma is difficult to control. PMID- 2320511 TI - Catch patients doing something right! PMID- 2320512 TI - A stranger in surgery. PMID- 2320513 TI - Diagnostic strategies for amenorrhea. AB - The diagnosis of amenorrhea may be perplexing because of the sheer number of possible causes and the complexity of the structures involved (ie, the CNS pituitary-ovarian axis). By using the same approach with all amenorrheic patients, rather than classifying them according to primary and secondary amenorrhea, physicians can narrow the diagnostic possibilities quickly and avoid unnecessary and expensive laboratory testing. Referral to a gynecologist or an endocrine specialist is recommended when the workup becomes overly complex. PMID- 2320514 TI - Arthritis of the hand and wrist. Management options for some common arthritic conditions. AB - Many arthritic conditions can affect the small joints of the hand and wrist. An understanding of the disease process helps in managing the problem. Conservative care generally consists of rest, splinting, use of anti-inflammatory drugs, intra articular injection with corticosteroids, and rehabilitation therapy. Surgical procedures for the arthritic hand are reserved for persistent cases of pain or instability that do not respond to conservative treatment. PMID- 2320515 TI - Anaphylaxis and life-threatening allergic reactions. PMID- 2320516 TI - Silent myocardial infarction. PMID- 2320517 TI - Management of the acute abdomen. A test of judgement. AB - Most patients with abdominal pain do not need an operation, but identification of those who do is an important role for the primary care physician. A carefully performed physical examination in conjunction with selected laboratory tests usually establishes the general diagnosis and allows the physician to decide among management alternatives. These include early operation, observation, or further evaluation using special studies. PMID- 2320518 TI - Cholesterol emboli syndrome following cardiac catheterization. AB - Cholesterol emboli syndrome should always be considered in an elderly patient with acute renal failure or cutaneous lesions following an invasive vascular procedure or surgery. Laboratory findings that suggest atheroemboli include eosinophilia, an elevated erythrocyte sedimentation rate, leukocytosis, and anemia. Diagnosis is made by biopsy of the affected organ, and treatment is supportive. Patients usually die of multisystem failure. PMID- 2320519 TI - Head and neck symptoms. Is the problem in the ears, face, neck, or oral cavity? AB - There is a complex anatomic and physiologic relationship among head and neck structures. Because of this complexity, patients with problems in any of these structures often present with a wide range of symptoms and physical findings. The authors describe many head and neck conditions that are encountered in a busy practice and emphasize selection of diagnostic studies and appropriate referral for treatment. PMID- 2320520 TI - Gene taught me to try. PMID- 2320521 TI - Transient neurologic symptoms. Narrowing the vast field of causes. AB - Transient neurologic symptoms are common in clinical practice and can take many forms (eg, loss of consciousness, confusion, vertigo, seizures, drop attacks, behavioral abnormalities). They are often subtle and episodic and their source can be the central nervous, cardiovascular, metabolic, or endocrine system, or they can be caused by space-occupying lesions. A detailed knowledge of such symptoms and their possible causes is invaluable to confidently approach the problem in a systematic manner. Evaluation should begin with careful history taking and physical examination for intercurrent illness and a baseline set of tests. Investigation usually includes computed tomography of the brain and often magnetic resonance imaging, cerebrospinal fluid analysis, and/or electroencephalography as well. Further, specific studies are chosen on the basis of the suspected diagnosis and the information being sought. PMID- 2320522 TI - The relative biological value of feed phosphates for chicks. AB - Two experiments were conducted to determine the relative biological values (BV) of phosphorus in feed phosphates. Experiment 2 was a replicate of Experiment 1, except that an additional phosphate source was tested. Within experiments, each treatment was replicated twice. Each pen contained eight broiler cockerels. The experimental diets were composed primarily of corn and soybean meal. The reference phosphate [anhydrous, reagent-grade, dibasic calcium phosphate (AR DCP)] was added to supply five levels of phosphorus. Each phosphate supplement was added to supply two levels of phosphorus. A regression equation was calculated based on logarithm g, nonphytate phosphorus per kilogram of diet versus the percentage of bone ash from chicks fed diets containing AR-DCP. Nonphytate phosphorus equivalents were calculated using the percentage of bone ash from chicks fed the test phosphates. The biological values of the test phosphates were determined as nonphytate phosphorus equivalents, minus the nonphytate phosphorus in the basal diet, divided by the amount of supplemental phosphorus. The BV obtained for the commercial phosphates in Experiments 1 and 2 were: dibasic calcium phosphate, 106 and 104; monobasic calcium phosphate. 102 and 104; defluorinated phosphate (DFP)-1, 88 and 90; and DFP-2, 100. PMID- 2320523 TI - Influence of neuraminidase on fertility and on sperm storage in the hen's oviduct. AB - Preinsemination incubation of semen with neuraminidase (4 IU/2 x 10(9) spermatozoa) significantly reduced fertility in one out of two trials. No differences were observed in fertility between semen treated with 4 versus 8 or 4 versus 16 IU of neuraminidase in Trials 1 or 2. All three levels of neuraminidase (4, 8, or 16 IU) removed the same amount (about 45%) of the bound sialic acids from spermatozoa during incubation. The removal of sialic acid from spermatozoa had a slight but nonsignificant affect on sperm storage within the uterovaginal (UV) sperm-host glands. Hens inseminated with neuraminidase-treated spermatozoa had decreased numbers of full and partially full UV sperm-host glands and increased numbers of empty glands, compared to hens inseminated with untreated but incubated spermatozoa. In the present study, reduced fertility resulting from the treatment of spermatozoa with neuraminidase from Clostridium perfringens indicates the desirability of exploring the use of other neuraminidases to see whether a correlation exists between the amount of sialic acid removed from spermatozoa and their subsequent fertility. PMID- 2320524 TI - Selective denervation of the Musculus pectoralis muscle in the chicken. AB - A surgical method for selective denervation was developed to facilitate investigations about the postmortem characteristics of denervated pectoralis muscles in chickens, Musculus (M.) pectoralis. The M. pectoralis was denervated in anesthetized chickens unilaterally or bilaterally by excising a 1-cm section of the nervus pectoralis as it branched from the N. medianoulnaris in the brachial plexus. Denervation resulted in significant (P less than .01) and consistent depression in the relative weight of M. pectoralis from the wk 2 through 17 postoperative. The relative weight of the functionally antagonistic M. supracoracoideus was unaffected by ipsilateral denervation of the M. pectoralis. The M. coracobrachialis acts in synergism with the M. pectoralis and displayed significant muscle atrophy at 4, 6, 8 and 17 wk postoperative in treatment groups where the ipsilateral M. pectoralis was denervated. Only the M. pectoralis displayed histological signs of denervation in transverse cryostat sections. Denervated tissue was characterized by atrophic and rounded muscle-fiber profiles, an increase in the endomysial and perimysial connective-tissue spaces, and leucocytes within degenerative perimysial nerves from 2 through 17 wk postoperative. Signs of denervation were distributed throughout seven zones sampled from the M. pectoralis. This study indicated that selective denervation of the M. pectoralis was achieved and that postoperative histology was necessary to accurately assess denervation. PMID- 2320525 TI - Fertility following intrauterine insemination near the time of oviposition. AB - The fate and fertility of semen deposited immediately following oviposition in the vicinity of the uterovaginal sperm host glands (USHG) was evaluated and compared with the semen deposited in the vagina. Intrauterine insemination of hens immediately after oviposition provided excellent fertility over a 2-wk period, compared to semen deposited in the vagina; also, 89% of the eggs laid within 25 h following intrauterine insemination were fertile, versus 33% following intravaginal insemination. Thus, spermatozoa deposited in the vicinity of the USHG immediately following oviposition (to simulate a release of spermatozoa from this region) can be transported to the infundibulum and effectively fertilize the next ovum ovulated. While some spermatozoa deposited in the uterus are transported to the infundibulum, the bulk of those retained in the oviduct populate the USHG. Thus, oviductal contractions immediately following oviposition do not adversely influence either the retention of spermatozoa or their incorporation into the USHG if the spermatozoa are placed on the uterine side of the uterovaginal junction. PMID- 2320526 TI - Effect of intermittent lighting on the reproductive performance of first-year and recycled turkey hens. AB - In each of two trials, a 2-by-2 factorial arrangement of treatments was utilized to evaluate the reproductive performance of first-year and recycled turkey hens to intermittent lighting (IL) through an egg-laying period of 20 wk. The IL treatment provided 4 h of light per day given as 2 h light:12 h dark:2 h light:8 h dark (2L:12D:2L:8D). This treatment group was compared to controls maintained on 16L:8D. Data were collected for BW, feed intake, feed efficiency, time to first egg, eggs per hen fertility, hatchability, egg weight, and poult weight. Consistent age effects included greater BW, egg weight, and poult weight from recycled hens compared to first-year hens as well as a delay in the onset of laying and a reduction in egg production by six eggs per hen in the recycled hens. Feed intake and feed efficiency were similar in both age groups, Intermittent lighting delayed the onset of laying but increased the rate of lay by eight eggs per hen. Late-season fertility, feed efficiency, and egg weight were significantly increased by the IL treatment. The conclusion was that, for turkey hens, intermittent lighting can effectively improve reproductive performance. PMID- 2320527 TI - Effects of high-energy electron irradiation of chicken meat on Salmonella and aerobic plate count. AB - Four experiments were used to determine the effects of high-energy irradiation on the number of aerobic microorganisms and Salmonella on broiler breasts and thighs. Irradiation ranging from 100 to 700 kilorads (krads) was provided by a commercial-scale, electron-beam accelerator. Irradiation of broiler breast and thigh pieces with electron beams at levels of 100, 200, 300, 400, 500, and 600 krads showed that levels as low as 100 krads would eliminate Salmonella. When 33 thighs were tested after irradiation at 200 krads, only one thigh tested presumptive positive. The total number of aerobic organisms was reduced by 2 to 3 log10 cycles at irradiation levels of 100, 200, 300, 400, 500, 600, and 700 krads. Increasing the dose above 100 krads gave little if any additional benefit. PMID- 2320528 TI - Examination of the physical characteristics in a diverse group of dwarf White Leghorn pullets before and after first oviposition. AB - The purpose of the present experiment was to measure changes in physical variables with sexual maturity (SM), the oviposition of first egg, in sex-linked dwarf pullets when SM was delayed by the photoschedule. Offspring were produced from matings of dwarf Single Comb White Leghorn chickens divergently selected for high (H) or low (L) 20-wk BW. At 15 wk of age, pullets from half-sibling sets were randomly assigned to a diet either of low energy (LE: 2,500 kcal/kg of ME, 15% CP) or high energy (HE: 3,000 kcal/kg of ME, 15% CP) and were placed in cages. When a pullet reached SM, the mature (M) pullet and an immature (I, absence of oviposition), half-sibling pullet on the same diet were sampled for BW as well as for the weights of abdominal fat, liver, ovary, oviduct, whole egg (M pullets), yolk, and shell and for the number of rapidly developing follicles. Proximate measurements (wet weight) were made for defeathered carcasses and livers as well as for ovaries and oviducts. There were significant (P less than or equal to .01) line effects for BW at SM (H greater than L); age at SM (L greater than H); weights for the liver, abdominal fat, egg, albumen, shell (H greater than L), and yolk (L greater than H); number of developing follicles (H greater than L); percentage of carcass protein (L greater than H) and of fat (H greater than L); as well as for liver protein (L greater than H), fat (H greater than L), and ash (L greater than H). There were significant (P less than .01) diet effects for abdominal fat (HE greater than LE) and shell weight (LE greater than HE). There was a line-by-diet interaction for total feed intake and for total energy intake from 15 wk to oviposition of the first egg. There were significant (P less than .01) SM effects (M greater than I) for BW at SM, number of developing follicles, oviduct weight, and fat content of the reproductive organs; also, reproductive organ weights accounted for differences in BW at SM. There was an interaction for line by maturity state; the L pullets showed a greater increase in ovarian weight with oviposition of the first egg than did the H pullets. The results of this study indicated that the threshold requirements for BW, composition, or both, for SM may have been exceeded in Leghorn-type chickens when photoscheduling was used to delay the onset of SM. PMID- 2320529 TI - The effect of tamoxifen on sexual puberty of turkey toms and Muscovy drakes. AB - The effects of Tamoxifen (TAM) on reproductive traits in young turkey toms and Muscovy drakes were studied. At 6 wk of age, five toms were injected every other day with 1 mg TAM/kg BW, while six others were treated with corn oil (controls). In the toms, using TAM advanced semen production by 4 wk (13.5 versus 17.5 wk of age) and increased the size of the snood and testes. Similarly, in the Muscovy drake, using TAM enhanced penis growth and advanced semen production by 5 wk. PMID- 2320530 TI - Reproduction responses of broiler-breeders to anticoccidial agents. AB - Two experiments were conducted to determine the effects of anticoccidial agents on production and reproduction of broiler breeders. In Experiment 1, nicarbazin (NCZ) was fed at 20, 50, and 100 ppm. There was no depression in egg production, egg weight, or fertility from feeding these levels. As level of NCZ increased, there was a linear decrease in hatchability. The amount of 4,4' dinitrocarbanilide (DNC) in the egg yolks increased linearly as the levels of NCZ went up; the degree of egg-shell depigmentation was directly related to the level of NCZ fed starting at 50 ppm. Experiment 2 utilized a different strain of broiler breeders. Halofuginone (3 ppm), maduramicin (5 ppm), monensin (100 ppm), narasin (70 ppm), NCZ (125 ppm), robenidine (33 ppm), and salinomycin (60 ppm) were fed to broiler breeders at the levels listed. Only NCZ reduced egg production. Narasin induced a reduction in egg weight. Both narasin and salinomycin caused a significant drop in hatchability. Feeding NCZ also induced a rapid and more severe decrease in hatchability. Monensin was the only anticoccidial agent that reduced fertility. Halofuginone, maduramicin, and robenidine had no biologically significant effect on henday production, egg weight, hatch of fertile eggs, or shell depigmentation. Feeding NCZ at 125 ppm caused a complete bleaching of brown-shell eggs by the 3rd consecutive day of treatment; but 7 days after NCZ was withdrawn from the feed, pigmentation returned to the pretreatment level. PMID- 2320531 TI - Effect of feeding diets containing corn treated with a commercial mold inhibitor (Myco Curb) on broiler-breeder performance. AB - Corn purchased from commercial sources was split at delivery and was left untreated or treated with a commercial mold inhibitor. Feed was prepared from these two lots of corn from within 1 wk to as much as 20 wk after delivery over the course of two experiments. There was evidence of reduced mold growth due to the mold inhibitor, particularly in the second experiment where initial mold populations were higher. Mycotoxins were evident in feed samples, regardless of the corn treatment. There was no significant effect from the treatment of corn on growth, livability, egg production, feed conversion, egg weight, or the eggshell quality of broiler breeders. Treatment of corn with a mold inhibitor significantly increased hatchability of fertile eggs in both experiments. Fertility was also significantly improved in the second experiment. These data suggest that using corn treated with a mold inhibitor results in significantly better hatchability in broiler breeders than untreated corn, although there were no observed differences in the incidence of mycotoxins in the samples taken. PMID- 2320532 TI - Effects of the presence or absence of satellite chick-waterers in conjunction with nipple-drinkers on the mortality and productive performance of broiler chicks from young and old dams. AB - Two runs of one experiment were conducted to study the effects of the presence or absence of satellite (SAT) chick-waterers in conjunction with nipple-drinkers on the mortality and productive performance of mixed-sex, broiler chicks grown to 42 days of age. Data were combined for analysis. The chicks were obtained from dams 29, 31, 61 and 65 wk of age. The treatments were: 1) chicks from 61- and 65-wk old dams, nipple-drinkers only; 2) chicks from 29- and 31-wk-old dams, nipple drinkers only; 3) chicks from 61- and 65-wk-old dams, nipple-drinkers plus one SAT-waterer per replication; 4) chicks from 29- and 31-wk-old dams, nipple drinkers plus one SAT-waterer. The SAT waterers were removed after 11 days. Routine management procedures were followed. The chicks from the older dams (61 and 65 wk of age) were heavier (1.60 versus 1.58 kg, P less than .05) tha those from the young dams (29 and 31 wk of age). Chicks from the young dams had better feed conversion (1.89 versus 1.93 g/g, P less than .01). The age of dam had no effect on the mortality of the broiler chicks. The presence or absence of SAT waterers had no effect on body weight or feed conversion. A difference (P less than .05) occurred in mortality through 42 days of age; the chicks using the SAT waterers had a lower mortality level (3.23 versus 4.22%), than those using nipple drinkers. The presence of ST-waterers in conjunction with nipple-drinkers appears to improve livability in broiler chicks. PMID- 2320533 TI - Diclazuril, a new broad-spectrum anticoccidial for chickens. 3. Floor-pen trials. AB - Diclazuril is a benzeneacetonitrile showing great promise as a broad-spectrum anticoccidial agent for chickens, turkeys, and rabbits. The high anticoccidial activity of diclazuril in chickens, as first reported in dose-titration studies and battery trials, was confirmed in three floor-pen trials. The efficacy was demonstrated against six major pathogenic species of Eimeria after artificial infection with one or more species. The experimental data indicated that diclazuril, at dose levels of .5, .75, 1, and 2 ppm, had a high anticoccidial activity in terms of preventing mortality, suppressing or reducing lesion scores, and allowing for normal weight gains as well as productivity. The performances obtained with diclazuril was generally comparable with that of salinomycin at 60 ppm and that of lasalocid at 90 ppm. PMID- 2320534 TI - Genetic control of interleukin-2-like activity is distinct from that of mitogen response in chickens. AB - Two genetic model systems, consisting of a series of sublines differing in linkage between the B blood group (Ea-B) and a gene that encodes immune response to glutamic acid-alanine-tyrosine (Ir-GAT) and a series of highly inbred lines of chickens, were used to examine the relationship between genetic control of levels of interleukin-2-like (IL-2-like) activity and genetic control of mitogen response to concanavalin A (Con A). Results obtained by using the highly inbred lines suggested that levels of IL-2-like activity were associated with levels of mitogen response to Con A. Results obtained by using the Ea-B/Ir-GAT sublines, however, suggested that levels of IL-2-like activity were not associated with the mitogen response to Con A. Levels of IL-2-like activity were associated with Ea-B but not with Ir-GAT, whereas the mitogen response to Con A was associated with both. High levels of IL-2-like activity were demonstrated in birds that had low levels of mitogen response to Con A. Previous genetic events that have occurred within these sublines may have resulted in the dissociation of genetic control of levels of IL-2-like activity and the response to the blastogenesis-inducing mitogen. This demonstrates the independence of genetic control of IL-2-like activity from that of proliferative response to the inducing mitogen. PMID- 2320535 TI - Evaluation of corn gluten feed in the diets of laying hens. AB - The use of corn gluten feed (CGF) in the diets of laying hens and in induced molting programs was investigated through four experiments. The first two experiments evaluated the effects of CGF on egg production from 23 to 56 or from 32 to 65 wk of age. Graded levels of CGF from 0 to 25% were added to a corn soybean meal, control diet (16.5% CP) in a nonisocaloric and an isocaloric manner. The ratio for dietary MEn:protein was held constant in some diets, but varied in others. The nonisocaloric inclusion of up to 25% CGF did not negatively affect egg production in either experiment. When 25% CGF was fed to the 32 wk old hens, egg weight was decreased. Egg weight was also decreased when 10% CGF or higher levels were fed to the younger hens. The nonisocaloric addition of CGF also increased feed intake and decreased feed efficiency (gram of egg per gram of feed) in most cases. Isocaloric inclusion of 15% CGF did not affect egg production parameters, but 25% CGF negatively affected most parameters. When the ratio for MEn:protein of the CGF diets was equal to that of the control diet, 25% CGF negatively affected most parameters, 17.5% CGF decreased egg weight and feed efficiency, and 10% CGF increased egg production. Feed intake was increased at all of the CGF levels. Two additional experiments evaluated CGF in programs for induced molting. The molting procedure involved feed withdrawal for 10 days followed by feeding molt diets consisting of 99.75% corn, 99.75% CGF, 49.75% corn:50% CGF, or two grower-type diets for pullets (15% CP) containing 25% CGF or 18.5% wheat bran. The two grower-type diets for pullets yielded similar and significantly greater postmolt gains in body weight and early postmolt egg production (3 wk) than did the other diets. The corn:CGF diet also yielded greater postmolt weight gains and early postmolt egg production than the 100% corn or 100% CGF diets. Long-term postmolt egg production (30 or 37 wk) was not affected by the molt diets. PMID- 2320536 TI - Energy exchange of two breeds of hens in respiration chambers. AB - The heat production for two breeds of laying hens was estimated by indirect respiration calorimetry. Using multiple linear regression techniques, egg energy output was identified as a significant contributor to variability in heat production (P = .0113). Heat production of the hens decreased with increasing egg energy output. Body weight, feed intake, egg energy output, and genetic stock were all significant contributors to variability in heat production. Comparisons of traditional techniques (relating energy balance to metabolizable energy intake) and multiple regression techniques (heat production as a function of body weight, feed intake, egg energy output, and genetic stock) for evaluating calorimetry data were made. PMID- 2320537 TI - The life span perspective: a developmental approach to community health nursing. AB - Following the nursing theorists' tradition of using an interdisciplinary approach to community health model building, the concepts of the life span perspective on human development were applied to the practice of community health nursing. As with the perception of individual development from this perspective, communities are viewed as evolving over time, with changes occurring across levels of influence--human, societal, historical, and cultural. These levels are interdependent, and factors from any one or more can affect the growth and functioning of the community. Implied in this interdependence is the ability not only to intervene in a community's development, but to go beyond this and recognize that a community has a degree of control over its own development. To be accurate and thorough in working with communities, the community health nurse who takes a life span perspective must be cognizant of the fact that communities do exist in a continual, multilevel, interactive manner that develops through time. Demonstrating the practical use of this perspective, a model for the assessment phase of the nursing process as applied to community study was developed. A pilot study was performed using this model, and initial results suggest that taking a life span perspective toward community health is both valid and practical, and warrants further scholarly investigation. PMID- 2320538 TI - Adolescent parents and toddlers: strategies for intervention. AB - Adolescents share many developmental similarities with toddlers. When an adolescent becomes a mother, the parent-toddler relationship is affected by the level of development of both individuals. It may be nurturing and satisfying, or it may be conflicted and frustrating for both. By comparing the developmental similarities the two share, the nurse is provided with a framework for assessing and working with these clients. PMID- 2320539 TI - Clinical competencies for community health nursing. AB - Cost-containment strategies initiated in the early 1980s caused a major shift in site of care delivery for persons needing nursing care. Where once the majority of clients were cared for in the acute-care setting until they were self sufficient, now most are discharged to the home environment still requiring acute care nursing interventions as well as community health nursing skills. This rapid shift in practice sites has placed severe strain on community health nursing agencies. Not only are more nurses required to fill the increased demand for services, but the demand comes at a time when we are experiencing a severe nursing shortage. This has forced many agencies to hire acute care nurses who have little or no community health nursing experience. These nurses come to community health nursing expecting to use the same set of skills and knowledge base used in their acute-care practice; however, the skill levels and concepts required for community health nursing are quite different from the acute care setting. Educational preparation has not kept pace with this shift in practice. Consequently, many nurses are not adequately prepared to enter community health nursing. Preparation must include theoretical and experiential components that focus on assessment skills (of the community and individual), decision making, case management, health systems management, teaching, and leadership. Collaborative efforts between community health organizations and educational institutions would seem to be one solution that would ensure adequately prepared nurses for community health nursing. The establishment and maintenance of strong staff-development programs within community health nursing agencies are also required. PMID- 2320540 TI - The resource dependence of a county nursing department: efforts to thrive in the 1980s. AB - This case study documents analysis and planning in a contemporary public health nursing organization using resource dependence organizational theory. Several internal and external factors affect the organization and its relationships with its resources. We attempted to use knowledge of the environment-organization relationship in several ways. Three examples from inside and outside the county system demonstrate opportunities for nursing to decrease the organization's traditional resource dependence and expand its base of funding and influence. Application of this theory can assist other organizations to adapt and survive in this era of diminishing health care resources. PMID- 2320542 TI - Challenge for general practice in 1990. PMID- 2320544 TI - Diabetic clinics: setting up. PMID- 2320543 TI - A child with learning difficulties. PMID- 2320545 TI - New perspectives in asthma self-management. PMID- 2320541 TI - Public health nursing: cross-training in core services. AB - Diminishing financial-resources and increasing demands for health care precipitated one public health district to review its framework of delivery of care for effective and efficient use of personnel and facilities. Categorical funding patterns had promoted a framework that functioned along specialized programmatic lines in which were identified inequities in funding and staffing, and use of services by clients. In addition, to the often inefficient use of staff and fragmentation of patient care were the associated consequences of overcrowded clinics, long waiting lists for appointments, and chronic understaffing of some clinics. The concept of cross-training in core services was initiated in one health center in October 1985. It was based on the belief that the best of generalized and specialized approaches to health care delivery in this district could be merged, and that all nursing staff should be proficient in certain basic functions. Results indicate improved efficiency in clinic management and flow, leading to reduced costs per patient encounter, increased demands for service that were met with existing staff, and reduced patient waiting time. PMID- 2320546 TI - Consumer-sensitive medicine. PMID- 2320547 TI - Common zoonoses. PMID- 2320548 TI - Zoonotic skin diseases. PMID- 2320549 TI - Animal disease: the real risks. PMID- 2320550 TI - Vegetarianism and health. PMID- 2320551 TI - Conformational changes in human serum albumin induced by ligand binding. PMID- 2320552 TI - 1st Nordic Conference of Toxicology and 8th annual meeting of NordEMS. NORDTOX 90. Beito Mountain Resort, Norway, 21-25 March, 1990. Abstracts. PMID- 2320553 TI - Social class disparities in risk factors for disease: eight-year prevalence patterns by level of education. AB - This article examines the associations between education, a primary indicator of social class, and six risk factors for disease. Data are presented on a sample of 3,349 individuals ages 25-74 years who participated in one of four cross sectional surveys conducted by the Stanford Five-City Project between 1979 and 1986. The six risk factors examined are knowledge about health, cigarette smoking, hypertension, serum cholesterol, body mass index, and height. A highly significant pattern of associations was found between education level and the six risk factors, in the direction of higher risk among those with lower education (all P values less than 0.01). These associations persisted for both sexes and in the younger as well as the older age groups, with the exception of cholesterol values for males and for those in the 50 to 74-year-old age group. Furthermore, all associations remained highly significant after controlling for income and occupation, two other indicators of social class. When a summary-adjusted risk score was plotted against year of survey for the five education levels, a gradient of effect was observed where each progressive education level showed a decrease in total risk score. This gradient was replicated in all four cross sectional surveys, providing evidence for the consistency of the findings over time. PMID- 2320554 TI - From preventive policy to preventive practice. AB - Characteristics of the relationship of preventive policy to preventive practice are reviewed. The relatively low emphasis on prevention compared with treatment programs is discussed and the particular problem of the "anonymity" of prevention is defined. Prevention programs suffer in part because of the lack of identity of the specific individuals benefited. Examples from the cardiovascular diseases are used to illustrate the general points. The contrast between community- and patient-oriented prevention is important. Adequate levels of disease prevention and health promotion will never be attained one case at a time. Interactions among individuals are determinants of environmental behavioral factors relevant to health. The policy forming process is intrinsically interactive in nature. The Institute of Medicine's 1988 study of the future of public health is reviewed with respect to its emphasis on professional participation in the health policy process. Prevention is an essentially multidisciplinary area requiring the participation of many professions and disciplines. This property of prevention will be enhanced in the future. Ten principles which can be useful in translating preventive policy into preventive practice are presented. PMID- 2320555 TI - Worksite health promotion: its evolution and the Johnson & Johnson experience. AB - Worksite health promotion, a rapidly growing form of preventive health service, may include health risk appraisal with communication of findings to the individuals tested. It may also assist in achieving and maintaining physical and mental fitness, controlling alcohol use, avoiding or quitting tobacco and other drugs, and otherwise maintaining health protective habits, while providing opportunities to control high blood pressure, and reduce elevated blood cholesterol, obesity, and other health hazards. This article presents a synopsis of the evolution of that movement and reviews the experience of one industrial firm that has endeavored to document and evaluate its effort. Such a review may be helpful in consolidating the various findings to date and in indicating the complexity of assessing the health and economic consequences of such an endeavor in private companies. PMID- 2320556 TI - Primary prevention of cardiovascular diseases in childhood: changes in serum total cholesterol, high density lipoprotein, and body mass index after 2 years of intervention in Jerusalem schoolchildren age 7-9 years. AB - A school health education and promotion program, the Israeli version of the American Health Foundation's "Know Your Body" program, was developed by the Department of Public Health of the Municipality of Jerusalem in 1983. Eight experimental and eight control schools participated in this cohort study of Arab and Jewish first-grade children. After the first 2 years of intervention, comparison of experimental and control groups showed a significant increase in serum high density lipoproteins among Jewish children and a decrease in serum total cholesterol and body mass index among both Jewish and Arab children. These results indicate that changes in cardiovascular disease risk factors such as blood total cholesterol, high density lipoproteins, and body mass index are possible after a health education program is introduced to first-grade students for a relatively short period of time. PMID- 2320557 TI - Dietary protein and blood pressure in monozygotic twins. AB - Cross-sectional studies relating blood pressure to dietary intake have shown equivocal results, in part due to the inability to take into account the strong genetic component of blood pressure. Intervention studies, using the same subject as his own control, often encounter additional problems when subjects are asked to adhere to an alternate diet. The National Heart, Lung, and Blood Institute Twin Study of middle-aged men provided information concerning the possible relationship of food-frequency-estimated nutrient intake to blood pressure while controlling for genetic effects in a free-living group of subjects. Using differences in monozygotic twins, a direct association of dietary protein intake and diastolic blood pressure was identified and persisted after adjustment for known covariates of blood pressure. Adjusting for known covariates and holding total calories constant, a 9-g difference in daily protein intake was directly associated with a 1 mm Hg difference in diastolic blood pressure. For protein intake as a percentage of total calories, a 2.18% difference was directly associated with a 1 mm Hg difference in diastolic blood pressure. The co-twin control method provides a powerful design to address the interrelationships between nutrients and blood pressure in an observational as well as an experimental setting. PMID- 2320558 TI - Biased appraisal of high blood pressure. AB - Two experiments were conducted to determine the effects of individuals' beliefs concerning their own blood pressure level on their appraisals of the seriousness of high blood pressure. In Experiment 1, 40 college students had their blood pressure measured and were randomly assigned to receive either high or normal blood pressure feedback. Afterward, they were asked to rate the seriousness of high blood pressure. Subjects who were given high blood pressure feedback rated the disorder as a less serious threat to health than did those subjects who received normal feedback. The results were replicated in Experiment 2 among a second sample of college students. Experiment 2 also revealed that minimization is associated with the belief that hypertension is an acute or cyclical condition. These experimental findings confirm clinical evidence that minimization is a common initial reaction to threatening medical information. PMID- 2320559 TI - The value of current nutrition information. AB - To prevent or delay the occurrence of chronic diseases, scientific bodies from the cardiologic and oncologic disciplines have made recommendations regarding the daily dietary intake of certain macro- and micronutrients. This study assessed the knowledge of a random population of 2,305 individuals comprising members of the public, health care workers, university graduate students, and health club attendees. Segments of this population might be expected to have a greater understanding and ability to implement these dietary recommendations. We found that over 90% of the participants were unaware of the recommendations for calcium, salt, vitamin A, and fiber, and the fiber content in a high fiber cereal. Approximately 80% of the participants were unaware of the recommendations regarding fat intake and could not calculate the fat content of a food product. Almost half of the study population took a vitamin pill daily. Of the subjects who were aware of the correct unit measurement for vitamin A (IU), almost 25% of gave a response that exceeded the recommended daily intake. A majority of this study population were unaware of the dietary recommendations regarding the prevention of cardiovascular events and cancer. Subgroups of this study population that might be expected to have more information regarding these recommendations (i.e., having higher education or being a health care professional) did not display a satisfactory level of knowledge. To further compound the problems of adhering to the recommended guidelines, the labeling of many food products is misleading. The recommendations on dietary intake and the information on food product content must be transmitted to the public in a form that allows for ready application when purchasing and consuming food. PMID- 2320560 TI - Lipid profiles of Yanomamo Indians of Brazil. AB - To determine serum lipid levels and their correlates in one of the world's most isolated populations, 62 adult Yanomamo Indians from the Amazonian rain forest were examined. After measurement of body weight and height, and estimation of age, casual blood samples were obtained. Estimated age ranged from 20 to 68 years, with men averaging 37 and women 35 years. Mean serum total cholesterol was very low among both men (123 mg/dl) and women (142 mg/dl) compared with western samples, whereas triglycerides--112 and 110 mg/dl, respectively--were lower among men and slightly higher among women than for U.S. men and women. Yanomamo women had significantly higher total cholesterol (P = 0.02) and body mass index (BMI) (P = 0.05) than men. HDL-cholesterol (P = 0.08) and LDL-cholesterol (P = 0.21) were also somewhat higher among women. Multivariate regression analysis indicated that estimated age was independently related to cholesterol in both sexes, while BMI was of borderline significance. The very low serum lipid levels in this isolated population are apparently attributable mainly to their largely vegetarian diet, low in fats and cholesterol and high in fiber, with concomitant high physical activity associated with low BMI. PMID- 2320561 TI - Preventive cardiology: what lies ahead? AB - Despite increased knowledge of the leading causes of cardiovascular diseases, we continue to observe rather than to control the rise and fall of their incidence. Research needs to be more oriented toward current uncertainties of policy: Is a high-fat diet acceptable so long as its polyunsaturated to saturated fat ratio is high? What are the long-term adverse effects of the powerful new cholesterol lowering drugs? Should people eat more polyunsaturates? Can new understanding of clotting factors help to prevent heart attacks? How can we lower the average blood pressure of the population as a whole? How do maternal and child health influence the next generation's cardiovascular health? The new research to answer such questions requires that epidemiologists abandon the "black box" approach (which ignores mechanisms); instead, basic scientists need to explain the actions of environmental agents. A new style of preventive clinical practice is emerging, but its future success depends on changes in the medical care system (involving structure, rewards, and staffing), changes in medical education, and on the willingness of physicians to negotiate shared responsibility with their patients. Physicians can identify and help high-risk individuals; but because the incidence of heart disease depends on how people live, it follows that progress in prevention ultimately depends on social, economic, and political decisions. By successful communication of knowledge and impartial advice, physicians can assist in those decisions. PMID- 2320562 TI - Proteinaceous inhibitors of phospholipase A2 purified from inflammatory sites in rats. AB - We have purified two phospholipase A2 inhibitory proteins (37 and 33 kDa) from peritoneal fluid of dexamethasone-treated rats. The extracellular phospholipase A2 found in inflammatory sites differed from the exocrine phospholipase A2 in susceptibility to these endogenous inhibitors; both proteins inhibited the activity of the extracellular phospholipase A2 purified from sites of inflammation but did not affect appreciably the activity of either porcine pancreatic or Naja naja venom phospholipase A2. The amino acid sequence of the NH2-terminal portion of the purified proteins did not resemble that of lipocortins so far reported, but it was almost identical to that of parts of human or mouse complement component C3. These findings may indicate that degraded products of C3 are involved in the regulation of activity of a class of mammalian phospholipase A2. PMID- 2320564 TI - A simple genealogical structure of strongly balanced allelic lines and trans species evolution of polymorphism. AB - Different alleles undergoing strong symmetric balancing selection show a simple genealogical structure (allelic genealogy), similar to the gene genealogy described by the coalescence process for a sample of neutral genes randomly drawn from a panmictic population at equilibrium. The only difference between the two genealogies lies in the different time scales. An approximate scaling factor for allelic genealogy relative to that of neutral gene genealogy is [square root of S/(2M)].[In[S/(16 pi M2)]]-3/2, where M = Nu and S = 2Ns (N, effective population size; u, mutation rate to selected alleles per locus per generation; s, selection coefficient). The larger the value of square root of S/M (greater than or equal to 100), the larger the scaling factor. These findings, supported by simulation results, allow one to apply the theoretical results of the coalescence process directly to the allelic genealogy. Combined with the trans-species evolution of the major histocompatibility complex polymorphism for which balancing selection is believed to be responsible, allelic genealogy predicts that the number of breeding individuals in the human population could not be as small as 50-100 at any time of its evolutionary history. The analysis appears to contradict the founder principle as being important in recent mammalian evolution. PMID- 2320563 TI - A clonal theory of parasitic protozoa: the population structures of Entamoeba, Giardia, Leishmania, Naegleria, Plasmodium, Trichomonas, and Trypanosoma and their medical and taxonomical consequences. AB - We propose a general theory of clonal reproduction for parasitic protozoa, which has important medical and biological consequences. Many parasitic protozoa have been assumed to reproduce sexually, because of diploidy and occasional sexuality in the laboratory. However, a population genetic analysis of extensive data on biochemical polymorphisms indicates that the two fundamental consequences of sexual reproduction (i.e., segregation and recombination) are apparently rare or absent in natural populations of the parasitic protozoa. Moreover, the clones recorded appear to be stable over large geographical areas and long periods of time. A clonal population structure demands that the medical attributes of clones be separately characterized; ubiquitous clones call for priority characterization. Uniparental reproduction renders unsatisfactory Linnean taxonomy; this needs to be supplemented by the "natural clone" as an additional taxonomic unit, which is best defined by means of genetic markers. PMID- 2320565 TI - The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome. AB - The X chromosome-linked scurfy (sf) mutant of the mouse is recognized by the scaliness of the skin from which the name is derived and results in death of affected males at about 3-4 weeks of age. Consideration of known man-mouse homologies of the X chromosome prompted hematological studies, which have shown that the blood is highly abnormal. The platelet and erythrocyte counts are both reduced and become progressively lower relative to normal as the disease progresses. There is gastrointestinal bleeding, and most animals appear to die of severe anemia. By contrast, the leukocyte count is consistently raised. Some animals showed signs of infection but it is not yet clear whether there is immunodeficiency. Other features include the scaly skin and apparently reduced lateral growth of the skin, conjunctivitis, and diarrhea in some animals. The mutant resembles Wiskott-Aldrich syndrome in man, which is characterized by thrombocytopenia, eczema, diarrhea, and immunodeficiency. The loci of the human and mouse genes lie in homologous segments of the X chromosome, although apparently in somewhat different positions relative to other gene loci. Scurfy differs from Wiskott-Aldrich syndrome in that scurfy males are consistently hypogonadal. PMID- 2320566 TI - Expression of recombinant glutathione S-transferase pi, Ya, or Yb1 confers resistance to alkylating agents. AB - Increased levels of glutathione S-transferase (GST; RX:glutathione R-transferase; EC 2.5.1.18) mRNA, protein, and activity in tumor biopsy samples and in drug resistant cultured cells are associated with resistance to anticancer drugs. We report that each of three full-length cloned GST cDNAs, that for pi (acidic), Ya (basic), and Yb1 (neutral), can confer drug resistance when expressed in cultured mammalian cells. In one approach, stably transfected mouse C3H/10T1/2 cells that express GST pi, Ya, or Yb1 were cloned and analyzed for drug resistance in colony forming assays. Transiently transfected COS cells that were sorted on a fluorescence-activated cell sorter were used in the second approach to avoid interclonal variation in factors other than the recombinant GST and to show that reversion of transient GST expression correlated with loss of drug resistance. A sorting technique, developed to separate the 20% of the electroporated COS cell population that transiently expressed GST pi, Ya, or Yb1 from the nonexpressing population, was based on a GST-catalyzed intracellular conjugation of glutathione to the fluorescent labeling reagent monochlorobimane. GST Ya conferred the greatest increase in resistance to chlorambucil and melphalan (1.3- to 2.9-fold), Yb1 conferred the greatest increase in resistance to cisplatin (1.5-fold), and pi conferred the greatest increase in resistance to a racemic mixture of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene and 7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene and doxorubicin (1.5- and 1.3-fold) relative to controls. These resistance values to alkylating agents are commensurate with values observed clinically. Cytotoxicity curves representing recombinant GST+ populations were significantly different from their controls with P values ranging from 0.005 to 0.0001. No resistance to vinblastine was detected. Conferred drug resistance was proportional to the magnitude of GST Ya expression, and reversion of transient expression in GST Ya+ COS cell clones to a GST Ya- phenotype was associated with total loss of drug resistance. PMID- 2320567 TI - Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: implications for etiology and therapy. AB - Brain regions from patients with or without Alzheimer disease (AD) were obtained within 2 hr of death and examined for indices of presynaptic cholinergic function. Consistent with loss of cholinergic projections, cerebral cortical areas involved in AD exhibited decreased choline acetyltransferase (acetyl CoA:choline O-acetyltransferase, EC 2.3.1.6) activity. However, remaining nerve terminals in these regions displayed marked up-regulation of synaptosomal high affinity [3H]choline uptake, a result indicative of relative cholinergic hyperactivity. As choline uptake is also rate-limiting in acetylcholine biosynthesis, these findings have implications for both therapy and identification of causes contributing to neuronal death in AD. PMID- 2320568 TI - Effect of thyroid hormone on the accumulation of mRNA for skeletal and cardiac alpha-actin in hearts from normal and hypophysectomized rats. AB - Skeletal alpha-actin gene products are coexpressed with cardiac alpha-actins in cardiac tissue of adult humans, cows, and pigs; in prenatal rats; and during hypertrophy due either to increased hemodynamic load or the administration of alpha-adrenergic agonists. Because there is preferential synthesis of the beta myosin heavy chain in each case, it has been suggested that the synthesis of skeletal alpha-actin in cardiac tissue is linked to that of beta-myosin heavy chain. To test this hypothesis, thyroid hormone, which causes cardiac hypertrophy with preferential synthesis of alpha-myosin heavy chain, was administered to normal and hypophysectomized rats. Animals were sacrificed from 2 to 24 hr after the injection of either 1 or 5 micrograms of hormone per 10 g of body weight. The relative amount of mRNA for skeletal and cardiac alpha-actin was measured by using the technique of primer extension. Thyroid hormone caused a rapid increase in the amount of skeletal alpha-actin mRNA relative to controls, more than 7 times in hearts from normal animals and 15 times in hearts from hypophysectomized animals. A small increase in cardiac alpha-actin mRNA also occurred. The rapid increase in transcripts for skeletal alpha-actin under conditions where the isoform of myosin heavy chain that is being synthesized is primarily alpha demonstrates independent patterns of activation of the actin and myosin heavy chain multigene families during cardiac growth in mammals. PMID- 2320569 TI - Platelet glycoprotein IIb-IIIa protein antagonists from snake venoms: evidence for a family of platelet-aggregation inhibitors. AB - The purification, complete amino acid sequence, and biological activity are described for several homologous snake venom proteins that are platelet glycoprotein (GP) IIb-IIIa antagonists and potent inhibitors of platelet aggregation. The primary structures of kistrin (from Agkistrodon rhodostoma), bitan (from Bitis arietans), three isoforms of trigramin (from Trimeresusus gramineus), and an isoform of echistatin (from Echis carinatus) were determined by automated sequence analysis and fast atom bombardment mass spectrometry analysis. Each of the protein in this family, which range from 47 to 83 residues, contains an Arg-Gly-Asp amino acid sequence found in protein ligands that binds to GPIIb-IIIa, a high (17 +/- 1%) cysteine content conserved in the primary sequence, and a homologous N-terminal region absent only in the echistatin isoforms. Each protein directly inhibits the interaction of purified platelet GPIIb-IIIa to immobilized fibrinogen about 100 times more effectively than does the pentapeptide Gly-Arg-Gly-Asp-Ser; IC50 values range from 1.1 to 3.0 nM. The IC50 value for the inhibition of platelet aggregation, using human platelet-rich plasma stimulated with ADP, ranges from 110 to 550 nM for the various proteins, about 1000-fold more potent than Gly-Arg-Gly-Asp-Ser. Kistrin binds reversibly to both resting and ADP-activated human platelets with high affinity (Kd = 10.8 nM and 1.7 nM, respectively) and to purified GPIIb-IIIa with a lower affinity (Kd = approximately 100 nM). Finally, kistrin injected at 1.0 mg/kg into rabbits reversibly inhibits platelet aggregation ex vivo over 30 min without induction of thrombocytopenia. We propose that these proteins are members of a general class of proteins found in the venom of pit vipers that inhibit platelet aggregation by antagonism of the GPIIb-IIIa-fibrinogen interaction and as such serve as potential antithrombotic agents. PMID- 2320570 TI - DNA "fingerprinting" reveals high levels of inbreeding in colonies of the eusocial naked mole-rat. AB - Using the technique of DNA fingerprinting, we investigated the genetic structure within and among four wild-caught colonies (n = 50 individuals) of a eusocial mammal, the naked mole-rat (Heterocephalus glaber; Rodentia: Bathyergidae). We found that DNA fingerprints of colony-mates were strikingly similar and that between colonies they were much more alike than fingerprints of non-kin in other free-living vertebrates. Extreme genetic similarity within colonies is due to close genetic relationship (mean relatedness estimate +/- SE, r = 0.81 +/- 0.10), which apparently results from consanguineous mating. The inbreeding coefficient (F = 0.45 +/- 0.18) is the highest yet recorded among wild mammals. The genetic structure of naked mole-rat colonies lends support to kin selection and ecological constraints models for the evolution of cooperative breeding and eusociality. PMID- 2320571 TI - Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases. AB - The antioxidant properties of tryptophan and some of its oxidative metabolites were examined by measuring how efficiently they inhibited peroxyl radical mediated oxidation of phosphatidylcholine liposomes and B-phycoerythrin. Low micromolar concentrations of 5-hydroxytryptophan, 3-hydroxykynurenine, xanthurenic acid, or 3-hydroxyanthranilic acid, but not their corresponding nonhydroxylated metabolic precursors, scavenged peroxyl radicals with high efficiency. In particular, 3-hydroxykynurenine and 3-hydroxyanthranilic acid protected B-phycoerythrin from peroxyl radical-mediated oxidative damage more effectively than equimolar amounts of either ascorbate or Trolox (a water-soluble analog of vitamin E). Enzyme activities involved or related to oxidative tryptophan metabolism, as well as endogenous concentrations of tryptophan and its metabolites, were determined within tissues of mice suffering from acute viral pneumonia. Infection resulted in a 100-fold induction of pulmonary indoleamine 2,3-dioxygenase (EC 1.13.11.17) as reported [Yoshida, R., Urade, Y., Tokuda, M. & Hayaishi, O. (1979) Proc. Natl. Acad. Sci. USA 76, 4084-4086]. This was accompanied by a 16- and 3-fold increase in the levels of lung kynurenine and 3 hydroxykynurenine, respectively. In contrast, endogenous concentrations of tryptophan and xanthurenic acid did not increase and 3-hydroxyanthranilic acid could not be detected. The activity of the superoxide anion (O2-.)-producing enzyme xanthine oxidase increased 3.5-fold during infection while that of the O2 .-removing superoxide dismutase decreased to 50% of control levels. These results plus the known requirement of indoleamine 2,3-dioxygenase for superoxide anion for catalytic activity suggest that viral pneumonia is accompanied by oxidative stress and that induction of indoleamine 2,3-dioxygenase may represent a local antioxidant defence against this and possibly other types of inflammatory diseases. PMID- 2320572 TI - Molecular structure of nicked DNA: a substrate for DNA repair enzymes. AB - The molecular structure of a nicked dodecamer DNA double helix, made of a ternary system containing d(CGCGAAAACGCG) + d(CGCGTT) + d(TTCGCG) oligonucleotides, has been determined by x-ray diffraction analysis at 3 A resolution. The molecule adopts a B-DNA conformation, not unlike those found in intact dodecamer DNA molecules crystallized in a somewhat different crystal lattice, despite a gap due to the absence of a phosphate group in the molecule. The helix has a distinct narrow minor groove near the center of the molecule at the AAAA region. This suggests that the internal stabilizing forces due to base stacking and hydrogen bonding interactions are sufficient to overcome the loss of connectivity associated with the disruption of the covalent backbone of DNA. PMID- 2320573 TI - Isolation of a 5-kilodalton actin-sequestering peptide from human blood platelets. AB - Resting human platelets contain approximately 0.3 mM unpolymerized actin. When freshly drawn and washed platelets are treated with saponin, 85-90% of the unpolymerized actin diffuses out. Analysis by polyacrylamide gel electrophoresis under nondenaturing conditions shows that the bulk of this unpolymerized actin migrates with a higher mobility than does pure G-actin, profilactin, or actin gelsolin complex. When muscle G-actin is added to fresh or boiled saponin extract, the added muscle actin is shifted to the high-mobility form. The saponin extract contains an acidic peptide having a molecular mass in the range of 5 kDa, which has been purified to homogeneity by reverse-phase HPLC. This peptide also shifts muscle actin to the high-mobility form. Addition of either boiled saponin extract or the purified peptide to muscle G-actin also strongly and stoichiometrically inhibits salt-induced polymerization, as assayed by falling ball viscometry and by sedimentation. We conclude that this peptide binds to the bulk of the unpolymerized actin in platelets and prevents it from polymerizing. PMID- 2320574 TI - Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect. AB - Saposins are small, heat-stable glycoproteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Saposins A, B, C, and D are derived by proteolytic processing from a single precursor protein named prosaposin. Saposin B, previously known as SAP-1 and sulfatide activator, stimulates the hydrolysis of a wide variety of substrates including cerebroside sulfate, GM1 ganglioside, and globotriaosylceramide by arylsulfatase A, acid beta galactosidase, and alpha-galactosidase, respectively. Human saposin B deficiency, transmitted as an autosomal recessive trait, results in tissue accumulation of cerebroside sulfate and a clinical picture resembling metachromatic leukodystrophy (activator-deficient metachromatic leukodystrophy). We have examined transformed lymphoblasts from the initially reported saposin B-deficient patient and found normal amounts of saposins A, C, and D. After preparing first strand cDNA from lymphoblast total RNA, we used the polymerase chain reaction to amplify the prosaposin cDNA. The patient's mRNA differed from the normal sequence by only one C----T transition in the 23rd codon of saposin B, resulting in a threonine to isoleucine amino acid substitution. An affected male sibling has the same mutation as the proband and their heterozygous mother carries both the normal and mutant sequences, providing additional evidence that this base change is the disease-causing mutation. This base change results in the replacement of a polar amino acid (threonine) with a nonpolar amino acid (isoleucine) and, more importantly, eliminates the glycosylation signal in this activator protein. One explanation for the deficiency of saposin B in this disease is that the mutation may increase the degradation of saposin B by exposing a potential proteolytic cleavage site (arginine) two amino acids to the amino-terminal side of the glycosylation site when the carbohydrate side chain is absent. PMID- 2320575 TI - Immunological properties of hepatitis B core antigen fusion proteins. AB - The immunogenicity of a 19 amino acid peptide from foot-and-mouth disease virus has previously been shown to approach that of the inactivated virus from which it was derived after multimeric particulate presentation as an N-terminal fusion with hepatitis B core antigen. In this report we demonstrate that rhinovirus peptide-hepatitis B core antigen fusion proteins are 10-fold more immunogenic than peptide coupled to keyhole limpet hemocyanin and 100-fold more immunogenic than uncoupled peptide with an added helper T-cell epitope. The fusion proteins can be readily administered without adjuvant or with adjuvants acceptable for human and veterinary application and can elicit a response after nasal or oral dosing. The fusion proteins can also act as T-cell-independent antigens. These properties provide further support for their suitability as presentation systems for "foreign" epitopes in the development of vaccines. PMID- 2320576 TI - Characterization of amplification core and esterase B1 gene responsible for insecticide resistance in Culex. AB - Organophosphorus insecticide (OP) resistance in several Culex species is associated with increased esterase activity resulting from amplification of the corresponding structural gene. In Culex pipiens quinquefasciatus, high levels of OP resistance (approximately 800 times) are due to the esterase B1 gene, which is amplified at least 250-fold. This gene has now been sequenced, and the structure of the amplification unit (amplicon) encompassing the structural gene has been partially characterized. The inferred amino acid sequence of the enzyme revealed regions of strong homology with other eukaryotic serine-esterases, such as cholinesterases, which are the target of OPs. The amplicon covers at least 30 kilobases and contains a constant and highly conserved "core" of 25 kilobases. This core carries a single copy of the esterase gene (2.8 kilobases) as well as other sequences that are present as single or low number copies in the genomes of mosquitoes lacking overproduction of the esterase B1 protein. In the amplicon, the esterase gene is framed by two DNA sequences that are repeated in other parts of the genome of resistant mosquitoes and found in the genome of susceptible mosquitoes but not near the esterase B1 gene. It is suggested that these repetitive sequences may have a role in the amplification process. PMID- 2320577 TI - Molecular and genetic characterization of a radiation-induced structural rearrangement in mouse chromosome 2 causing mutations at the limb deformity and agouti loci. AB - Molecular characterization of mutations in the mouse, particularly those involving agent-induced major structural alterations, is proving to be useful for correlating the structure and expression of individual genes with their function in the whole organism. Here we present the characterization of a radiation induced mutation that simultaneously generated distinct alleles of both the limb deformity (ld) and agouti (a) loci, two developmentally important regions of chromosome 2 normally separated by 20 centimorgans. Cytogenetic analysis revealed that an interstitial segment of chromosome 17 (17B- 17C; or, possibly, 17A2-17B) had been translocated into the distal end of chromosome 2, resulting in a smaller than-normal chromosome 17 (designated 17del) and a larger form of chromosome 2 (designated 2(17). Additionally, a large interstitial segment of the 2(17) chromosome, immediately adjacent and proximal to the insertion site, did not match bands 2E4-2H1 at corresponding positions on a normal chromosome 2. Molecular analysis detected a DNA rearrangement in which a portion of the ld locus was joined to sequences normally tightly linked to the a locus. This result, along with the genetic and cytogenetic data, suggests that the alleles of ld and a in this radiation-induced mutation, designated ldIn2 and ajIn2, were associated with DNA breaks caused by an inversion of an interstitial segment in the 2(17) chromosome. PMID- 2320578 TI - Uptake of low density lipoproteins by human leukemic cells in vivo: relation to plasma lipoprotein levels and possible relevance for selective chemotherapy. AB - The success of cancer chemotherapy is dependent on the possibility to utilize biological differences between malignant and normal cells to selectively destroy the tumor cells. One such difference may be that of receptor-mediated cellular uptake of low density lipoproteins (LDLs). Previous studies have shown that leukemic cells from patients with acute myelogenous leukemia have elevated receptor-mediated uptake and degradation rates of plasma LDL in vitro compared to normal white blood and bone marrow cells, and that plasma cholesterol levels at diagnosis are inversely correlated with the LDL receptor activity of the malignant cells. An important question is whether the uptake of LDL by the leukemic cells is also increased in vivo. To evaluate the in vivo uptake of LDL, 11 adult patients with newly diagnosed acute myelogenous leukemia received an i.v. injection of [14C]-sucrose-labeled LDL. On degradation of [14C]sucrose-LDL, the radiolabeled sucrose moiety is known to remain trapped in the lysosomal compartment of the cells. After injection, radioactivity accumulated progressively for at least 12 hr in the leukemic cells. The uptake of radioactivity in vivo correlated with the rate of receptor-mediated degradation of 125I-labeled LDL by the leukemic cells assayed in vitro (r = +0.88, P less than 0.001). An inverse correlation between plasma LDL cholesterol concentrations and the in vivo cellular uptake of [14C]sucrose-LDL in whole blood (r = -0.76, P less than 0.01) indicates that the hypocholesterolemia is due to elevated LDL uptake by the leukemic cells. Postmortem biopsies from virtually all tissues were obtained from one patient, and the distribution of radioactivity revealed that the liver and bone marrow had accumulated most radioactivity; the adrenals had the highest uptake of label per gram of tissue weight. The results indicate that LDL may be used as a carrier targeting lipophilic cytotoxic drugs to leukemic cells. PMID- 2320579 TI - Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor. AB - Glioma-derived vascular endothelial cell growth factor (GD-VEGF) is a 46-kDa dimeric glycoprotein mitogen with apparently greater specificity for vascular endothelial cells than the well-characterized fibroblast growth factors. The GD VEGF cDNA sequence encodes a 190-amino acid residue subunit that is converted, by removal of an amino-terminal hydrophobic secretory leader sequence, to the mature 164-residue subunit characterized by direct amino acid sequencing. The GD-VEGF homodimeric subunit is homologous to the platelet-derived growth factor A and B chains and its oncogene homologue v-sis. PMID- 2320580 TI - Biophysical and biological activity of a synthetic 8.7-kDa hydrophobic pulmonary surfactant protein SP-B. AB - We have synthesized pulmonary surfactant apoprotein SP-B peptides by solid-phase chemistry and demonstrated their ability to enhance the surface-active properties of synthetic lipid mixtures. The synthetic peptides were reactive with antiserum generated against the native bovine surfactant peptide. Both peptides conferred surfactant-like properties to synthetic lipid mixtures as assessed by a Wilhelmy balance and pulsating bubble surfactometer. Likewise, mixtures of synthetic SP-B peptides and lipid restored compliance of isolated surfactant-deficient rat lungs. This work demonstrates the utility of SP-B as a functional component of pulmonary surfactant mixtures for treatment of respiratory distress syndrome or other disorders characterized by surfactant deficiency. PMID- 2320581 TI - Transcriptional activities in dry seed nuclei indicate the timing of the transition from embryogeny to germination. AB - To investigate processes regulating the reinitiation of growth and differentiation during seed germination, we have studied the transcriptional activities of sets of genes that are expressed at specific stages of embryogeny and post-germination in the higher plant Brassica napus L. We show that transcripts from a subset of the genes are elongated in nuclei isolated from dry seeds, indicating that these genes are competent to be transcribed in desiccated and quiescent mature embryos. Analysis of the specific transcripts produced in dry seed nuclei indicates that the changes in gene expression patterns associated with germination are not initiated during late embryogeny. The results suggest that the transition from an embryonic to a postgerminative program of development occurs after seeds are rehydrated. PMID- 2320582 TI - Proposed regulatory pathway encoded by the nodV and nodW genes, determinants of host specificity in Bradyrhizobium japonicum. AB - Bradyrhizobium japonicum is the root nodule endosymbiont of soybean (Glycine max), mung bean (Vigna radiata), cowpea (Vigna unguiculata), and Siratro (Macroptilium atropurpureum). We report the characteristics of a nodulation-gene region of B. japonicum that contributes only marginally to the bacterium's ability to nodulate soybean but is essential for the nodulation of the three alternative hosts. This DNA region consists of two open reading frames designated nodV and nodW. The predicted amino acid sequences of the NodV and NodW proteins suggest that they are members of the family of two-component regulatory systems, which supports the hypothesis that NodV responds to an environmental stimulus and, after signal transduction, NodW may be required to positively regulate the transcription of one or several unknown genes involved in the nodulation process. It seems likely that all host plants produce the necessary signal, whereas host specificity may be brought about by the product(s) of the gene(s) activated by NodW. PMID- 2320584 TI - Correspondence between sexual isolation and allozyme differentiation: a test in the salamander Desmognathus ochrophaeus. AB - Ethological reproductive isolation and genetic divergence across 26 protein loci were measured among populations of the salamander Desmognathus ochrophaeus in the southern Appalachian Mountains. Levels of ethological isolation varied from none to complete and were statistically significant for all but two pairings between populations inhabiting different mountain ranges. When geographic and genetic distances were treated as independent variables in multiple correlation analyses, they accounted for about half the variance in levels of ethological isolation. When genetic distance is held constant, the remaining relationship between ethological isolation and geographic distance is still statistically significant. When geographic distance is held constant, the remaining relationship between genetic distance and levels of ethological isolation is nonsignificant, as is the relationship between geographic distance and genetic distance when ethological isolation is held constant. Ethological isolation and genetic divergence evidently both reflect the gradual divergence of allopatric populations, but genetic distance is a poor predictor of ethological isolation in these salamanders. PMID- 2320583 TI - Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents. AB - Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x ray-sensitive derivative were transfected with a bovine papillomavirus (BPV) linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions. PMID- 2320585 TI - Solution conformations of the B-loop fragments of human transforming growth factor alpha and epidermal growth factor by 1H nuclear magnetic resonance and restrained molecular dynamics. AB - A restrained molecular dynamics simulation approach that explicitly includes the effect of the surrounding solvent molecules is applied to the NMR determination of the conformations of the B-loop fragments of human transforming growth factor alpha and epidermal growth factor. Backbone interproton distance restraints are obtained by using two-dimensional rotating frame nuclear Overhauser effect spectroscopy (ROESY). The simulations are carried out both in "vacuum" and in "water." The results are discussed in terms of the energetics, agreement with the NMR distances, and the flexibility of the peptides. PMID- 2320586 TI - Development of B-lineage cells in the bone marrow of scid/scid mice following the introduction of functionally rearranged immunoglobulin transgenes. AB - Mice homozygous for the mutation scid (scid mice) are severely immunodeficient and generally lack detectable numbers of pre-B, B, and T cells. This condition is believed to result from a defect in the mechanism responsible for rearrangement of immunoglobulin and T-cell receptor genes in developing B and T lymphocytes. To test this hypothesis and evaluate whether scid affects only the process of gene recombination, we introduced functionally rearranged immunoglobulin genes into the scid mouse genome. As scid mice appear to contain early lymphoid cells committed to the B lineage (pro-B cells), we asked whether the introduction of an IgM heavy-chain gene alone (mu-transgenic scid mice) or both IgM heavy- and kappa light-chain genes (mu kappa-transgenic scid mice) would allow further differentiation of scid pro-B cells into pre-B and B cells. We found that normal numbers of pre-B cells appeared in the bone marrow of mu-transgenic scid mice and that both pre-B and B cells appeared in the bone marrow of mu kappa-transgenic scid mice. However, in the latter case, the number of pre-B and B cells was 2- to 3-fold less than in the controls (mu kappa-transgenic scid heterozygotes) and few, if any, B cells were detectable in the peripheral lymphoid tissues. The implications of these results for the above hypothesis are discussed. PMID- 2320587 TI - Molecular cloning of a plant betaine-aldehyde dehydrogenase, an enzyme implicated in adaptation to salinity and drought. AB - Many plants, as well as other organisms, accumulate betaine (N,N,N trimethylglycine) as a nontoxic or protective osmolyte under saline or dry conditions. In plants, the last step in betaine synthesis is catalyzed by betaine aldehyde dehydrogenase (BADH, EC 1.2.1.8), a nuclear-encoded chloroplastic enzyme. A cDNA clone for BADH (1812 base pairs) was selected from a lambda gt10 cDNA library derived from leaves of salt-stressed spinach (Spinacia oleracea L.). The library was screened with oligonucleotide probes corresponding to amino acid sequences of two peptides prepared from purified BADH. The authenticity of the clone was confirmed by nucleotide sequence analysis; this analysis demonstrated the presence of a 1491-base-pair open reading frame that contained sequences encoding 12 peptide fragments of BADH. The clone hybridized to a 1.9-kilobase mRNA from spinach leaves; this mRNA was more abundant in salt-stressed plants, consistent with the known salt induction of BADH activity. The amino acid sequence deduced from the BADH cDNA sequence showed substantial similarities to those for nonspecific aldehyde dehydrogenases (EC 1.2.1.3 and EC 1.2.1.5) from several sources, including absolute conservation of a decapeptide in the probable active site. Comparison of deduced and determined amino acid sequences indicated that the transit peptide may comprise only 7 or 8 residues, which is atypically short for precursors to stromal proteins. PMID- 2320588 TI - Expression and state of phosphorylation of the retinoblastoma susceptibility gene product in cycling and noncycling human hematopoietic cells. AB - The product of the retinoblastoma susceptibility gene RB1 (Rb) is likely to function as an inhibitor of cell growth. Previous studies have suggested that certain growth-suppressing effects of Rb are exerted in G0/G1 phase and that phosphorylation can inactivate these functions. We tested this hypothesis by examining the expression and state of phosphorylation of Rb in several lineages of primary hematopoietic cells that spontaneously arrest in G0 phase. Resting lymphocytes were found to express only unphosphorylated Rb, but phosphorylation of Rb occurred as the cells entered S phase in response to mitogens. In contrast, although monocytes and granulocytes also expressed high levels of unphosphorylated Rb, these terminally differentiated cells did not phosphorylate Rb, nor could they exit from G1 phase in response to growth factors. Thus, Rb phosphorylation appears linked to the ability of a cell to synthesize DNA. In T and B lymphocytes, Rb protein increased 8-fold after stimulation, while RB1 RNA levels increased 2- to 4-fold. Nuclear run-on assays and measurement of RB1 RNA half-life in T cells suggested that the increased RNA abundance was, at least in part, due to increased RNA stability. By contrast, Rb protein levels did not increase in either monocytes or granulocytes after stimulation, although RB1 RNA levels did increase in monocytes. Thus, there are lineage-specific differences in both the regulation of Rb phosphorylation and RB1 gene expression in lymphoid and myeloid cells. PMID- 2320590 TI - Free electron laser irradiation at 200 microns affects DNA synthesis in living cells. AB - We describe the effect of a 200-microns wavelength free electron laser beam on the ability of asynchronized and synchronized mammalian tissue culture cells to incorporate tritiated thymidine. Compared to controls (unexposed cells), a significant proportion of exposed cells exhibited a reduction in isotope incorporation. The results suggest that this wavelength may affect DNA synthesis. PMID- 2320589 TI - d-Tubocurarine binding sites are located at alpha-gamma and alpha-delta subunit interfaces of the nicotinic acetylcholine receptor. AB - The competitive nicotinic antagonist d-[3H]tubocurarine was used as a photoaffinity label for the acetylcholine binding sites on the nicotinic acetylcholine receptor (AcChoR) from Torpedo. Irradiation with 254-nm UV light of AcChoR-rich membranes equilibrated with d-[3H]tubocurarine resulted in covalent incorporation into the alpha, gamma, and delta subunits that could be blocked by alpha-bungarotoxin or by carbamoylcholine. The concentrations of d [3H]tubocurarine required for half-maximal specific incorporation into the gamma and delta subunits were 40 nM and 0.9 microM, respectively, consistent with the dissociation constants for the high- and low-affinity binding sites (Kd = 35 nM and 1.2 microM). The concentration dependence of incorporation into alpha subunit was biphasic and consistent with labeling of both the high- and low-affinity d tubocurarine binding sites. The specific photolabeling of each AcChoR subunit was inhibited by carbamoylcholine with appropriate dose dependence. These results establish that, in addition to the alpha subunits, the gamma and delta subunits also contribute directly to the acetylcholine binding sites and that each binding site is at an interface of subunits. Because the AcChoR subunits are homologous and are arranged pseudosymmetrically about a central axis, the photolabeling results are inconsistent with an arrangement of subunits in the AcChoR rosette of alpha beta alpha gamma delta and indicate that either the gamma or delta subunit resides between the alpha subunits. PMID- 2320591 TI - Rapid cloning of HLA-A,B cDNA by using the polymerase chain reaction: frequency and nature of errors produced in amplification. AB - A method for cloning full-length HLA-A,B cDNA (1.1 kilobases) by using the polymerase chain reaction (PCR) is described. Six HLA-A,B alleles (HLA-A2, -A25, B7, -B37, -B51, and -B57) were cloned, and their structures were determined. Multiple PCR clones for each allele were sequenced to obtain both an accurate consensus sequence and an "authentic" clone having that sequence. Sequences from 50 clones encoding five different alleles permit assessment of the frequency and nature of PCR-produced errors. These include recombinations, deletions, and insertions in addition to point substitutions. Authentic clones were obtained at a frequency of between 30% and 70%, and analysis of three or four clones generally should be sufficient for characterization of an allele. PMID- 2320593 TI - Correlation in the discharges of neighboring rat retinal ganglion cells during prenatal life. AB - The spontaneous discharges of neighboring retinal ganglion cells were recorded simultaneously in anesthetized prenatal rats between embryonic days 18 and 21. We report here that in the majority of cases the firings of neighboring retinal ganglion cells are strongly correlated during prenatal life. Correlation in the discharges of neighboring cells during development has long been suggested as a way to consolidate synaptic connections with a target cell onto which they converge, a model first proposed by Hebb. Correlation in the activities of neighboring neurons in the retina could be the basis of developmental processes such as refinement of retinotopic maps in the brain and segregation of the inputs from the two eyes. PMID- 2320592 TI - Fibril in senile systemic amyloidosis is derived from normal transthyretin. AB - The amyloid fibril in senile systemic amyloidosis (SSA), like that of familial amyloidotic polyneuropathy, is derived from transthyretin (TTR). SSA, however, is a common disease, affecting to some degree 25% of the population greater than 80 years old. In familial amyloidotic polyneuropathy, the amyloidogenesis has been considered to depend on point mutations leading to TTR variants. We show that the TTR molecule in SSA, on the other hand, has a normal primary structure. Factors other than the primary structure of TTR must therefore be important in the pathogenesis of TTR-derived amyloid. PMID- 2320594 TI - A new feeder for powdered diets. AB - A new feeder for powdered diets was developed for use with small rodents. The feeder has unique advantages over commercially available feeders. Wastage is minimal, food intake can be measured, and it is adaptable to various rodent species and different types of powdered diets. This study describes and evaluates the new feeder using three animal groups--weanling rats, adults rats, and adult hamsters. In the rat studies, the rate of growth of weanling and adult rats fed commercial rat chow in pellet form using conventional feeders was the same as that of rats fed the same chow in meal form using the new feeders. Likewise in the hamster studies, the rate of growth of adult hamsters fed powdered semi synthetic diet from conventional glass jars was the same as those fed the same diet from the new feeders. The new feeders supplied the animals with a continuous supply of meal free of contamination from feces or urine. Unrecoverable spillage (wastage) was 1-2% of the amount of food given. The new feeders were easy to handle and clean, had ample capacity, and needed little attention. PMID- 2320595 TI - Phosphate transport after acute changes in total NAD content in renal proximal tubules. AB - Suspensions of proximal tubules were obtained by collagenase digestion of rat renal cortex followed by centrifugation on a percoll gradient. NAD content in tubules incubated at 37 degrees C was decreased by 40-60% compared with tubules incubated at 4 degrees C. This change occurred within 30 min and was maintained for up to 2 hr. Inhibitors of NAD hydrolysing enzymes prevented the depletion of cellular NAD at 37 degrees C. Acute changes in proximal tubule NAD content at 37 degrees C were not accompanied by changes in phosphate uptake by brush border membrane vesicles subsequently prepared from the same tubules. In contrast, incubation of tubules with parathyroid hormone (10(-6) M) produced the expected inhibition (20%) of brush border membrane transport of phosphate. One implication of these findings is that acute changes in total NAD content of proximal tubules at 37 degrees C may not influence the phosphate transport system in the renal brush border membrane. Other interpretations are discussed. PMID- 2320597 TI - Cranial nerve dysfunction in conscious galactosemic rats as measured by the auditory-evoked brainstem response. AB - The purpose of this study was to extend our previous work with the auditory evoked brainstem response and determine whether galactosemia would produce a functional neuropathy similar to that previously seen in streptozocin-induced diabetic rats. Sprague-Dawley male rats implanted with cortical electrodes received either normal chow (n = 17) or a 50% galactose diet (n = 17) for 5 weeks. Peak II latency of the auditory-evoked brainstem response, interpreted as a functional measure of the auditory nerve (VIII cranial) in rats, was significantly prolonged in galactose-fed rats relative to controls (P less than 0.05). These results demonstrate a functional deficit in the auditory nerves of galactosemic rats. The deficit in the auditory-evoked brainstem response of galactosemic rats is similar to our previous finding in streptozocin-induced diabetic rats. PMID- 2320596 TI - Requirement for progesterone priming and its long-term effects on implantation in the mouse. AB - At least 48 hr of progesterone (P4) priming has been documented to be essential for P4 and estrogen to initiate implantation in the rat. However, the length of this P4 priming requirement for implantation in the mouse has not been experimentally defined. Therefore, our first objective was to determine the length of P4-priming requirement for implantation in the mouse. Day 4 blastocysts were transferred into the uteri of Day 5 or Day 6 pseudopregnant mice that were ovariectomized on Day 1 (= vaginal plug) and treated with a single injection of P4 and 17 beta-estradiol (E2) only on Day 5, or a single injection of P4 on Day 5 followed by a second injection of P4 plus E2 on Day 6, respectively. Although none of the transferred blastocysts implanted in the uteri of P4-unprimed recipients, 46% of the transferred blastocysts implanted into the uteri of all recipients that were first primed with P4 24 hour prior to a second injection of P4 and E2. These results suggest that in contrast to the rat, the mouse uterus requires at most 24 hr of P4 priming before P4 and estrogen can initiate implantation. Our second objective was to determine whether P4 priming has a long term effect on implantation in the mouse. Our present results and those of others suggest that the mouse uterus is exposed to rising P4 levels for 24 hr prior to implantation on Day 4 of pregnancy. Therefore, in the present investigation, induction of implantation by an injection of P4 and E2 following 5 days of ovariectomy performed on Day 4 of pregnancy clearly suggests that once exposed to P4 for 24 hr, the mouse uterus retains a long-term effect, i.e., following P4 withdrawal for several days, 24 hr of initial P4 priming is no longer required for P4 and estrogen to initiate implantation. Our next objective was to explore whether this long-term effect of P4 priming on implantation can be prolonged and potentiated by increasing the length of initial P4 priming. Thus, when the mice were ovariectomized on Day 4 of pregnancy and treated with P4 beginning on Day 5 for 4 days, the long-term effect on implantation was prolonged (8 days vs 5 days following P4 withdrawal) and potentiated (94% vs 0% mice with implantation following 8 days of P4 withdrawal) as compared with those with no P4 priming after ovariectomy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2320598 TI - Lipolytic and antilipolytic effects of human growth hormone, its 20-kilodalton variant, a reduced and carboxymethylated derivative, and human placental lactogen on chicken adipose tissue in vitro. AB - The lipolytic and antilipolytic effects of human growth hormone (22K-hGH), its 20 kilodalton variant (20K-hGH), a reduced and S-carboxymethylated derivative (RCM hGH), and human placental lactogen were examined using chicken adipose tissue explants in vitro. Lipolysis, as determined by glycerol release, was stimulated by 22K-hGH (biosynthetic and pituitary derived), 20K-hGH (pituitary derived), and RCM-hGH (modified biosynthetic). These growth hormone preparations also exhibited similar antilipolytic activity (i.e., transient inhibition of glucagon-induced lipolysis). However, unlike human growth hormone, human placental lactogen neither stimulated lipolysis nor inhibited glucagon-stimulated lipolysis. Some augmentation of glucagon-stimulated lipolysis was observed in the presence of human placental lactogen. These results indicate that the disulfide bridges (Cys53----Cys165; Cys182----Cys189) and amino acid residues 32-46 of hGH are not required for lipolytic or antilipolytic activities of human growth hormone on chicken adipose tissue. PMID- 2320599 TI - In vitro regulation of mammary glucose-6-phosphate dehydrogenase activity by palmitoyl coenzyme A, acetate, and polyamines. AB - An in vitro study was conducted to determine whether bovine mammary glucose-6 phosphate dehydrogenase (G6PD) activity was regulated by palmitoyl coenzyme A (CoA), acetate, spermidine, and putrescine and whether these effects were dependent upon stage of lactation. Early lactation explants incubated in media containing palmitoyl CoA or acetate had reduced (P less than 0.01) G6PD activity compared with incubated control explants. G6PD activity in early lactation explants was reduced (P less than 0.05) when incubated with 5 microM palmitoyl CoA or 1 mM acetate compared with 25 microM palmitoyl CoA or 10 mM acetate. Spermidine (0.4 mM) reversed (P less than 0.05) palmitoyl CoA-induced inhibition of early lactation G6PD activity at 5 microM, but not at 25 microM palmitoyl CoA. G6PD activity in early lactation explants was decreased (P less than 0.05) when treated with putrescine (0.4 mM) compared with explants treated with spermidine. Addition of acetate in combination with 5 microM palmitoyl CoA reversed G6PD inhibition (P less than 0.05 for 1 mM and P less than 0.01 for 10 mM) while addition of either level of acetate in combination with 25 microM palmitoyl CoA failed to reverse G6PD inhibition. G6PD activity was higher (P less than 0.01) in early lactation than mid-lactation explants. No statistical differences (P greater than 0.1) were found among any treatments in explants from mid-lactation cows. We conclude that palmitoyl CoA and acetate will inhibit G6PD activity in early lactation, but not mid-lactation explants; addition of spermidine will reverse this inhibition. PMID- 2320601 TI - Dietary manipulation of mammary tumor development in adult C3H/Bi mice. AB - Chronic energy intake restriction (CEIR) in virgin female mice is one of the most effective ways of reducing significantly mammary adenocarcinoma in C3H/Bi mice, a strain which develops mammary adenocarcinoma associated with the murine mammary tumor virus spontaneously and at high incidence. In this study, the influence of chronic energy intake restriction imposed on fully mature (4- to 5-month-old), breeding female C3H/Bi mice was addressed, and the influence of energy intake where energy was derived largely from fat versus diets in which energy was derived largely from carbohydrates on tumor development and survival rate was investigated. The results show that chronic energy intake restriction can be delayed until full maturation and successful reproduction and still reduce significantly the incidence of mammary tumor development in this relatively short lived strain of mice. Our findings demonstrate that the overriding dietary factor controlling mammary tumor development in these experiments in C3H/Bi mice was the level of energy intake, regardless of the primary source of energy (fat or carbohydrates). PMID- 2320600 TI - Effects of iron repletion and correction of anemia on norepinephrine turnover and thyroid metabolism in iron deficiency. AB - The reversibility of the alterations in norepinephrine (NE) content and turnover in interscapular brown adipose tissue and heart of iron-deficient rats has not been demonstrated. We therefore examined NE metabolism in age-matched male Sprague-Dawley rats depleted of iron by dietary means and after repletion with iron dextran. Heart NE content was 58, 61, and 85% of controls at 0, 3, and 7 days after repletion, whereas interscapular brown adipose tissue-NE content was 87, 103, and 104% of controls. Fractional heart NE turnover was 225% greater in iron-deficient anemics than controls but normalized within 3 days. Interscapular brown adipose tissue NE turnover was 58%, 46%, and 20% above controls in iron deficient rats after 0, 3, or 7 days of iron repletion. Hematocrit returned to 80% of normal in 7 days. Liver triiodothyronine production also increased to 80% of control in this period. A second experiment used isovolemic exchange transfusion to examine the influence of anemia per se on these alterations in organ NE turnover. Acute correction of anemia in iron deficiency did not alter brown fat NE turnover. Heart NE turnover was significantly lower in anemic animals regardless of iron status. Defects in heart and brown fat NE metabolism are reversible within 7 days of iron treatment as are alterations in triiodothyronine production. Anemia per se has little effect on brown fat NE metabolism but does dramatically decrease heart NE content. PMID- 2320602 TI - Recombinant tumor necrosis factor-alpha chronically administered in rats: lack of cachectic effect. AB - Recombinant human tumor necrosis factor-alpha (rHuTNF) was injected into rats to test its reported cachectic effects. Rats were subcutaneously injected daily at 1730 hr with either saline or rHuTNF (0.25 mg/kg body wt) for either 5 or 14 days. Daily food intakes were significantly depressed only for the first day and first two days of rHuTNF injection in animals treated for 5 days and 14 days, respectively. There were no significant differences in daily body weights among the groups. Analysis of carcass composition revealed no significant differences in percentage of lipid or protein. Liver and inguinal pad weights were not significantly different. In vitro determination of lipogenesis showed it was enhanced in the inguinal pad and depressed in the liver only after 14 days of treatment. These results demonstrate that although in vivo rHuTNF may specifically alter tissue metabolism, it does not, by itself, result in a sustained cachectic effect. PMID- 2320603 TI - The nuclear-cytoplasmic [Ca2+] gradient in single mammalian vascular smooth muscle cells. AB - We studied the nuclear-cytoplasmic [Ca2+] gradient in single, freshly dispersed smooth muscle cells from the ferret portal vein, by means of fluorescence ratio imaging microscopy. Cells were loaded with the cell-permeant calcium indicator fura-2 AM. Caffeine and platelet-derived growth factor (PDGF) were used in order to mobilize Ca2+ from the sarcoplasmic reticulum. Basal levels of nuclear and cytoplasmic [Ca2+] were 299 +/- 51 nM and 141 +/- 23 nM respectively (n = 10, p less than 0.001). At 3 min after 10mM caffeine, nuclear [Ca2+] decreased to 117 +/- 13 nM (n = 10, p less than 0.001), cytoplasmic [Ca2+] also decreased to 75 +/ 11 nM (n = 10, p less than 0.001) and the nuclear-cytoplasmic difference was no longer significant (p greater than 0.05). Similarly, 300pM of PDGF also abolished the nuclear-cytoplasmic [Ca2+] gradient (n = 12, p greater than 0.1). We conclude that in single muscle cells from the ferret portal vein a perinuclear sarcoplasmic reticulum could be a factor that contributes to the high apparent nuclear Ca2+ levels either through a dynamic Ca2+ influx, or by a fura-2 signal in the sarcoplasmic reticulum masking the true nuclear [Ca2+]. PMID- 2320604 TI - Frontiers in smooth muscle research. Proceedings of the Emil Bozler International Symposium. Columbus, Ohio, May 19-20, 1989. PMID- 2320605 TI - Effects of protein kinase-M on skinned smooth muscle fibres. PMID- 2320606 TI - Control of calcium release in smooth muscle cells. PMID- 2320607 TI - Smooth muscle energetics: testing theories of crossbridge regulation. AB - Our results indicate that the kinetic "latch" model of Hai & Murphy is not very sensitive to the proportion of ATP assigned to crossbridges relative to that ascribed to MLC phosphorylation/dephosphorylation. Thus the basis for the relatively low efficiency of smooth muscle, attributed to high MLC phosphorylation/dephosphorylation in this model, remains open to question. Moreover, this model, or any model with mixed populations of crossbridges with differing cycle rates and/or high MLC phosphorylation/dephosphorylation rates is unlikely to account for the observed linearity of JATP and stress reported for many smooth muscles. Our studies comparing the heat production of intact and skinned smooth muscle indicate that the ATPase associated with myosin phosphorylation/dephosphorylation is unlikely to be a major factor in the tension cost of intact smooth muscle. Thus it would appear that energetics places considerable constraints on current theories of crossbridge regulation. Our modelling (Paul, 1989) suggests that it may be time to reevaluate Bozler's original hypothesis that a high attachment:detachment rate ratio for smooth muscle actin-myosin interaction may be sufficient to explain the energetics of smooth muscle. PMID- 2320608 TI - Intracellular free magnesium concentration in the taenia isolated from guinea-pig caecum. AB - The free [Mg]i in the guinea-pig taenia was estimated to be about 300 microM. The [Mg]i remained constant by simple removal of Ca, but reduced by removal of both Ca and Mg, reaching about 8 microM in 100 min. This recovered on Mg readmission. No clear recovery was observed in Na-free (K-substitute) solution containing 2.4mM Ca. Carbachol response was reversibly inhibited when [Mg]i decreased to less than 1/10 of the control. In K-free solution [Mg]i gradually increased to more than 500 microM in 100 min in the absence of Ca, but not in the presence of Ca. A Na-Mg exchange process seems to be playing an important role, in addition to a low permeability of the membrane to Mg, in the regulation of [Mg]i. PMID- 2320609 TI - Studies of longitudinal tissue impedance in various smooth muscles. PMID- 2320610 TI - The effect of tissue properties on smooth muscle mechanics. PMID- 2320611 TI - Tonic duodenal contractions--a process for regulation of duodenal transit? PMID- 2320612 TI - Peristalsis evoked in the intestine tube devoid of mucosa and submucosa. PMID- 2320613 TI - Signal transduction at adrenergic nerve terminal in guinea-pig mesenteric artery. PMID- 2320614 TI - Identification of four state models of regulation of contraction of smooth muscle. PMID- 2320615 TI - Elevated K turnover in mesenteric arteries from aldosterone-salt hypertensive rats. PMID- 2320616 TI - Elevated calcium-dependent K+ efflux in aorta from stroke prone-spontaneously hypertensive rat. PMID- 2320617 TI - Characterization of an endothelial-dependent response to oxygen in porcine coronary artery. PMID- 2320618 TI - Signal transduction in hypoxic pulmonary vasoconstriction (HPV). PMID- 2320620 TI - The refractory properties of mapped clock oscillators representing smooth muscle electrical oscillations. PMID- 2320619 TI - Modification by calyculin A of inward Ca currents in smooth muscle cells isolated from guinea pig taenia coli. PMID- 2320621 TI - Effect of calpain II on turkey gizzard muscle and structural dissection of cytoplasmic dense bodies by low ionic strength extraction. PMID- 2320622 TI - Hyperpolarization-activated channels in myometrium: a patch clamp study. PMID- 2320624 TI - Cytosolic pH changes in contracting canine trachealis smooth muscle. PMID- 2320625 TI - The effects of pH on urinary tract smooth muscle function. PMID- 2320626 TI - Oscillatory potentials recorded from walls of anal canal and urethrae in dogs. AB - 1. Oscillatory potentials were recorded from internal anal sphincters and from internal urethral sphincters in similarity and difference in their characteristics. similarity and difference in their characteristics. 2. Unexpected finding was the appearance of burst-and-pause alternation in male urethrae in contrast to continuous oscillation in female urethrae. 3. Stimulation experiments revealed that the internal anal sphincter was controlled by reciprocal spinal outflow; lumbar accrelation and sacral inhibition. But the recto-anal reflex, constantly observable in decerebrate dogs, was predominantly inhibitory, which was identical with sacral action. 4. The effect of ventral root stimulation upon urethral oscillation was 'identical' for lumbar and for sacral activations, even if it was excitatory or inhibitory, depending upon ongoing level of activity and upon stimulus parameters. Nevertheless, reciprocal activation between detrusor spike and urethral oscillation was observed during 'isometric voiding contractions'. The reason for this inconsistency was discussed. PMID- 2320623 TI - On the down-regulation of cross-bridges occurring as changes in the cycling rate during tonic smooth muscle contractions. AB - As regards cross-bridge down-regulation, the following statements may summarize the results of our experiments: 1) The time course of cross-bridge down regulation is the initial high turn-over rate followed by a continuous retardation without any distinct loss in force generation. These mechanisms allowed a rapid force development and an improvement in force maintenance. 2) Cross-bridge down-regulation was seen in the tracheal preparation of both the rat and the guinea pig. As indicated by the greater time constants of the post vibration force recovery, the cross-bridge cycling rate seems to be distinctly lower in the guinea pig than in the rat trachea. 3) Cross-bridge down-regulation only occurs in smooth muscle preparations with intact cell membranes. This result would seem to hint that the sarcoplasmatic calcium concentration and/or the intactness of the cell membrane might be essential for producing cross-bridge down-regulation. 4) The recovery from cross-bridge down-regulation requires a rest period of more than 10s. The cross-bridges remain down-regulated during this time even after an increase in the sarcoplasmatic calcium concentration which was induced by a subsequent stimulus. This result indicates that changes in the sarcoplasmatic calcium cannot explain all the problems arising during cross bridge down-regulation. PMID- 2320627 TI - Effects of isoproterenol and caffeine on calcium transients and action potentials in human ventricular cardiomyocytes. PMID- 2320628 TI - Chemical modification of sulfhydryl groups inhibits skeletal muscle contraction in frog. PMID- 2320629 TI - Accessibility of thiols in actin--a kinetic study with fluorescent maleimide probes. PMID- 2320630 TI - Negative surface charges provoke conformational change of membrane proteins and release of calcium from sarcoplasmic reticulum. PMID- 2320631 TI - Muscle shortening increases fatigue of canine diaphragm. PMID- 2320632 TI - Blood flow to skeletal muscle during postexercise muscle soreness in humans. PMID- 2320633 TI - Chloride distribution in rat extensor digitorum longus muscle. PMID- 2320634 TI - Mechanical interaction of smooth muscle crossbridges modulates actin filament velocity in vitro. PMID- 2320635 TI - Contingent suppression of tolerance to haloperidol: a dose-response analysis. AB - Rats were given injections of haloperidol (HAL; 0.625 or 2.5 mg/kg) either before (Before groups) or after (After groups) access to sweetened milk on alternate days. Controls (Saline groups) were given injections of saline. At biweekly intervals ("test days"), all groups were given pretest injections of the drug in order to monitor the development of tolerance in the After and Saline groups. Rats in the Before groups showed no tolerance to the initial suppression of milk intake. In contrast, rats in the After groups had greater intakes, although the level of intake declined on subsequent test days in the group given the lower dose. Rats in the Saline groups drank less on the test days than any of the other groups, suggesting that sensitization occurred. These results are consistent with previous findings (29) that tolerance to HAL is suppressed following pretest injections of the drug. The degree of suppression appears to be inversely related to the frequency of such injections. PMID- 2320636 TI - Dopaminergic alterations in cotreatments attenuating haloperidol-induced hypersensitivity. AB - Chronic treatment of the laboratory rat with haloperidol results in an increased stereotypic behavioral response to subsequent dopamine agonist challenge. This behavioral hypersensitivity (BH) is thought to reflect an increase in DA receptor number following chronic pharmacologic denervation. Using a cotreatment strategy, we demonstrate here that a variety of agents can attenuate or prevent the development of BH when administered chronically with haloperidol. Cotreatment with lithium and amantadine prevented the changes in DA biochemistry as well as the proliferation of DA receptors normally associated with chronic haloperidol treatment. Cotreatment with thioridazine or scopolamine did alter the changes in DA biochemistry normally associated with haloperidol treatment, but failed to attenuate the DA receptor proliferation. Taken together, these data suggest that mechanisms in addition to DA biochemical and receptor changes participate in the development and subsequent expression of BH. DA receptor proliferation must, therefore, be considered permissive to the development of BH. PMID- 2320637 TI - Dietary modulation of the anorectic potency of amphetamine. AB - The effects of intake of an amphetamine solution on food and fluid intakes, body weight (b.wt.) and feed efficiency (FE) were examined in rats fed either a high carbohydrate (HC) (65% of total calories) or high-fat (HF) (65% of total calories) diet. During a 17-day predrug period, neither caloric intake, fluid intake, b.wt. nor feed efficiency (FE) differed as a function of diet. When given a 0.1 mg/ml amphetamine sulfate (AMPH) solution as their sole source of fluid, rats in both diet groups decreased fluid intake by an equivalent amount. While diet did not influence AMPH intake, it did alter the drug's effects on caloric intake, b.wt. and FE. In both diet groups, rats drinking AMPH decreased caloric intake, b.wt. gain and FE relative to rats which drank water. However, rats fed the HC diet decreased caloric intake less, but lost more weight than rats fed the HF diet. Further, rats fed the HC diet displayed a rapid tolerance to the anorectic effects of AMPH, with no tolerance to the drug's effect on b.wt. In contrast, rats fed the HF diet suppressed caloric intake throughout the drug period, but weighed more than rats fed the HC diet. Thus, when drinking the AMPH solution, FE of rats fed the HC diet was significantly lower than that of rats fed the HF diet. When the drug was removed, rats eating the HC diet failed to alter caloric intake and b.wt. In contrast, rats fed the HF diet increased caloric intake and gained weight. These data indicate that dietary factors must be considered when evaluating the anorectic actions of psychopharmacological agents. PMID- 2320638 TI - Physical dependence induced by the voluntary consumption of morphine in inbred mice. AB - When given a two-bottle choice between gradually increasing morphine concentrations (in 0.2% saccharin) and plain tap water, C57BL/6J mice consumed almost 90% of their daily fluid intake from the morphine-saccharin bottle, while the DBA/2J strain, in contrast, consumed 13% or less from the morphine-saccharin solution. The C57BL/6J strain consistently consumed mean daily doses of morphine sulfate in excess of 200 mg/kg, which was sufficient to induce an easily discernable withdrawal syndrome upon removal of the morphine solution, either with or without naloxone challenge. Hypothermia, tremor, wet dog shakes, jumping, and diarrhea were prominent withdrawal signs. In separate experiments, the saccharin was removed from the morphine-containing bottle, yet the C57BL/6J mice continued to prefer the morphine solution over tap water. In complete contrast to the above, mice of the DBA/2J strain rejected the morphine-saccharin solution at the lowest concentration employed, and at no time did their mean daily morphine dose exceed 20 mg/kg. Thus, morphine-saccharin preference is strongly genetically determined, and a high degree of physical dependence can result in the morphine preferring strain. Palatability differences appear not to be the predominant explanation for these differences in morphine-saccharin consumption. PMID- 2320639 TI - Effects of sodium phenobarbital on motor activity and exploration in the mouse: development of tolerance and incidence of withdrawal responses. AB - Sodium phenobarbital (20 mg/kg) was without significant effect on exploratory head-dipping, but a higher dose (70 mg/kg) significantly reduced the number of head-dips and the time spent head-dipping 0.5 and 8 hr after acute administration. Tolerance developed rapidly, i.e., by day 7 of treatment, to these reductions. Both doses of phenobarbital significantly increased locomotor activity, the increase was more marked for the 70 mg/kg dose and for this dose was greater 8 hr after administration than 0.5 hr. No tolerance developed over 21 days of treatment to the increase in locomotor activity 0.5 hr after drug administration; some tolerance did develop by day 14 to the increase detected 8 hr after drug administration, but this is likely to be metabolic. After 21 days of treatment, sodium phenobarbital was withdrawn. Twenty-four hours after the last dose of 70 mg/kg there was a significant reduction in the time spent head dipping; there was also significant reduction in locomotor activity, which peaked 48 hr after the last dose. PMID- 2320640 TI - Catecholamines and the initiation of sexual behavior in male rats without sexual experience. AB - The purpose of the present experiments was to investigate the effects of modified catecholaminergic neurotransmission upon sexual behavior in inexperienced males. Such males are critically dependent on stimuli from the female in order to initiate sexual behavior, and catecholamines are known to modulate interactions with environmental stimuli. It was found that D-amphetamine, 0.5 and 1 mg/kg, and amfonelic acid, 0.25 and 0.5 mg/kg, reduced mount and intromission latencies. Pimozide, in doses between 0.25 and 1 mg/kg, and cis(Z)-flupentixol, 0.5 mg/kg, reduced the proportion of animals displaying sexual behavior. The noradrenergic neurotoxin DSP4 (50 mg/kg one week before behavioral observation) shortened intromission latency while the noradrenaline precursor threo dihydroxyphenylserine (10 mg/kg + carbidopa 50 mg/kg) increased mount and intromission latencies. In a test for social and exploratory behaviors it was found that amfonelic acid, in a dose of 0.5 mg/kg, augmented sniffing and rearing without affecting nonsexual interaction with a receptive female. Flupentixol (0.5 mg/kg) had a slight inhibitory effect on exploratory behavior and no effect on nonsexual interaction with a female. It is suggested that enhanced dopaminergic activity facilitates the initiation of sexual behavior due to an increased general arousal and not because of a specific effect on that behavior. The role of noradrenaline is less clear at present. PMID- 2320641 TI - Effects of cigarette smoking on subjective and brain evoked responses to electrical pain stimulation. AB - The effects of smoking two cigarettes on brain evoked potentials (EP) and subjective ratings (SR) of pain intensity to 3 levels of electrical skin stimulation were investigated in 14 female habitual smokers. Smoking increased EP amplitudes to all stimulus intensities, but did not alter SRs. Changes in SRs to intensities in the pain range, but not in the prepain range, were found to be negatively correlated with smoke inhalation as measured by expired alveolar carbon monoxide (CO) elevations. No significant EP-smoking inhalation correlations were observed. PMID- 2320642 TI - Sexual differentiation and the effects of alcohol on aggressive behavior in mice. AB - Male and female mice are differentially sensitive to the effects of alcohol on aggressive behavior. We investigated the role of testosterone during sexual differentiation in determining sex differences in alcohol effects on aggression. On the day of birth male mice were castrated or sham-operated. Neonatal female mice were injected with 250 micrograms of testosterone propionate (TP) or the oil vehicle. At approximately 75 days of age the mice which had not been gonadectomized at birth were gonadectomized. Control males and androgenized female mice then received 7.5 mm Silastic capsules containing testosterone, SC. Aggressive behavior toward an intruder was assessed following administration of ethanol (0.1-3.0 g/kg) or water, PO. Neonatally sham-gonadectomized male mice had a significant increase in aggressive behavior following administration of 1.0 g/kg alcohol, with no significant suppression of aggression at 3.0 g/kg. Neonatally androgenized female mice showed neither the male-typical response to adult testosterone and alcohol, nor did they show the female-typical response. Neonatally gonadectomized males showed an alcohol dose response curve that was similar to that of androgenized females. Postnatal testosterone did not appear to completely determine the male- and female-typical responses to alcohol on aggression. The critical period for this sexually dimorphic response to alcohol and testosterone may be primarily prenatal. PMID- 2320643 TI - Chronic treatment with ethanol or chlordiazepoxide alters the metabolism of chlordiazepoxide. AB - Although chronic ethanol administration in C57BL/6J mice did not cause an induction of ethanol metabolism, it altered the metabolism of chlordiazepoxide (CDP). Significantly lower blood levels of CDP, but higher levels of N-desmethyl CDP (NDCDP), were observed in ethanol-dependent mice compared to pair-fed controls during the first hour after CDP injection. Mice treated chronically with CDP showed significantly lower blood levels of CDP and NDCDP than pair-fed controls after a test dose of CDP. In response to an injection of ethanol, the CDP-dependent mice had lower blood alcohol levels (BAL) than the pair-fed controls, but the rate of fall of BAL was not different in the two groups. Thus, chronic CDP treatment affected the absorption and distribution of ethanol. These results provide a metabolic basis for the manifestations of CDP tolerance and ethanol cross-tolerance that have been reported in CDP-dependent mice. PMID- 2320644 TI - Facilitation of sexual behaviors in the male rat in the presence of stimuli previously paired with systemic injections of morphine. AB - Male rats were tested for sexual behaviors in an environment previously associated with injections of morphine. Both gonadally intact and castrated males displayed more frequent female-directed behavior, such as pursuit of the female, anogenital exploration, and partial mounts, and gonadally intact animals had shorter latencies to initiate copulation when tested for sexual behaviors in the environment previously associated with morphine. These results suggest that a conditioned state induced by stimuli previously paired with the positive incentive effects of an opiate drug can facilitate or modulate behaviors under the control of other primary positive incentives. PMID- 2320645 TI - A contingent, conditioned suppression of eating following chronic benzodiazepine induced hyperphagia. AB - While the hyperphagic effect of chloradizepoxide (CDP) has been reported by some to be enhanced with chronic drug treatment, the processes underlying this phenomenon are not well understood. In the present study, it was predicted that following chronic exposure to CDP-induced hyperphagia, animals given a placebo in place of their usual drug injection might be expected to exhibit evidence of a conditioned, drug-like response. Such a finding would then be consistent with an underlying process of behavioral sensitization. In Experiment 1a, Male Sprague Dawley rats were randomly assigned to one of two groups receiving intraperitoneal (IP) injections of either 5 mg/kg CDP (Group CDP) or physiological saline (1 ml/kg; Group SAL) administered over 15 drug treatment days. Thirty minutes after each injection, all animals were given 30 min access to sweetened condensed milk. A significant enhancement of CDP-induced hyperphagia was observed over treatment sessions, confirming an earlier report. Unexpectedly, in the Placebo Test, the CDP animals exhibited a supression of milk consumption relative to that of the SAL group. Using the same animals, this finding was successfully replicated in Experiment 1b. In Experiment 2, it was hypothesized that if this conditioned, drug-opposite response were to reflect the involvement of some underlying compensatory, homeostatic mechanism, then it should only be observable under food contingent conditions of chronic drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2320646 TI - Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference. AB - The effect of naloxone on voluntary ethanol intake was examined in rats which were selectively bred for oral ethanol preference (High Alcohol Drinking or HAD line). Rats of the HAD line were treated with naloxone in doses of 0.05-18.0 mg/kg b.wt. before access to water alone or to a free-choice between a 10% (v/v) ethanol solution and water. Naloxone suppressed water intake when water was presented as the sole source of fluid. In contrast, naloxone produced a dose dependent decrease in ethanol consumption, without altering water intake, when rats were given a free-choice between the ethanol solution and water. Selective suppression of ethanol consumption by naloxone was not attributable to changes in blood ethanol concentrations or ethanol elimination rates following naloxone treatment. It appears that although naloxone may attenuate the positively reinforcing properties of both ethanol and water, ethanol drinking is a subset of consummatory behaviors that is particularly sensitive to opioid receptor blockade. The results suggest that activation of the endogenous opioid system may be an important mechanism which serves to maintain continued ethanol drinking. PMID- 2320647 TI - Effects of 24-hr fasting on methamphetamine- and apomorphine-induced locomotor activities, and on monoamine metabolism in mouse corpus striatum and nucleus accumbens. AB - The effects of 24-hr fasting on the vertical (VMA) and horizontal (HMA) locomotor activities, on cage climbing activity and on brain monoamine-related substances, were examined using male ddY mice. Both the VMA and HMA increased with fasting, but not the cage climbing activity. Methamphetamine (2 mg/kg, SC) increased the VMA and HMA in both the feeding and fasting mice, whereas with apomorphine (0.1 mg/kg, SC) both decreased. Furthermore, pretreatment with haloperidol (0.025 mg/kg, SC) showed no influence on the methamphetamine-induced VMA increase in both the feeding and fasting mice. However, pretreatment with haloperidol inhibited the methamphetamine-induced HMA increase in both the feeding and fasting mice and showed a higher level of HMA in fasting mice than in feeding mice. When measuring brain monoamine-related substances, the DA, NE, 5-HT, and 5 HIAA levels in the corpus striatum increased, whereas the 3-MT levels decreased. The monoamine levels in the nucleus accumbens of fasting mice were the same as those in feeding mice, except for a decrease of the 3-MT level. These results suggest that the locomotor activity in fasting mice may be increased by a change in the sensitivity of dopaminergic neurons in the corpus striatum. PMID- 2320648 TI - Multidimensional scaling of subjective judgements of drug similarities among ketocyclazocine, morphine, cyclazocine, naloxone and placebo. AB - Profiles of the subjective and physiologic effects of opioid drugs in man cannot be assigned with precision to specific opioid drug-receptor interactions. We administered a set of training doses of ketocyclazocine, morphine, cyclazocine, naloxone and placebo to 10 drug-using volunteers and obtained similarity judgements between each of 2 test doses of the drugs and a training dose. These data were submitted to multidimensional scaling analysis (INDSCAL) using both neighboring cells estimates and root mean square estimates to estimate missing cells in the data matrices. The results of these analyses are convergent, appear valid and indicate that there are three drug dimensions expressed in this data set: morphine versus placebo and naloxone; cyclazocine and ketocyclazocine versus placebo and naloxone; and ketocyclazocine versus cyclazocine. We interpret this result as supporting evidence that in the set of five drugs studied, three subjective states are induced. PMID- 2320649 TI - Drug discrimination in rats successively trained to discriminate diazepam and pentobarbital. AB - In Phase 1, rats were trained to discriminate either diazepam or pentobarbital from the no-drug condition. Diazepam, pentobarbital, triazolam, meprobamate, and zopiclone occasioned 100% drug-lever responding in tests under both training conditions; but the generalization gradients determined under the pentobarbital training condition were shifted to the right of those determined under the diazepam training condition. In Phase 2, the training drugs were reversed for the two groups, as well as which lever was paired with drug or no drug, in an effort to produce greater specificity of the Phase 2 discrimination. In Phase 2 tests, the Phase 1 training drug occasioned responding on the Phase 2 drug lever in all rats, suggesting that retraining overrode the Phase 1 discrimination. There were indications, however, that Phase 1 training influenced Phase 2 responding: 1) Rats ceased responding partway through no-drug training sessions using the former drug lever, and criterion performance was somewhat more difficult to maintain in Phase 2. 2) In Phase 2, dose-effect curves determined under pentobarbital training were shifted even further to the right of those determined under diazepam training than in Phase 1. PMID- 2320650 TI - Preferences for opioids by the weight pulling method in rats. AB - The preference for morphine and codeine was studied by means of the antagonistic conflict behavior between the positive drive of drug intake and the negative drive of weight pulling in rats. An apparatus was developed in which rats were compelled to pull the weight for the intake of drug-admixed food. The experiments began with the preadministration of the drug through the repetition of CFF schedule. The schedule consisted of one choice trial between the intake of normal food and drug-admixed food followed by two consecutive forced trials, in which the rats were forced to take the drug-admixed food only. In the test trial, the findings were that the rats which had already shown a drug seeking behavior toward morphine or codeine pulled weight to take each drug and that the reinforcing effects of these drugs on the drug seeking behavior depended on the treatment period of these drugs. The reinforcing effect of codeine was weaker than one of morphine. It is suggested that the reinforcing effects of these opioids can be evaluated quantitatively by the weight pulling method in rats. PMID- 2320651 TI - Diazepam and discriminative motor control: acute, chronic and withdrawal effects. AB - Rats were trained to hold a force transducer operated with a paw so that it remained between upper and lower limits of a force band for a continuous 1.5-sec period to deliver each food pellet. Acute doses of diazepam impaired measures of this performance. Separate groups received chronic diazepam injections (6 mg/kg, IP) either presession (Before Group) or postsession (After Group), or presession vehicle (Vehicle Group). The After and Vehicle Groups demonstrated that neither chronic postsession diazepam, nor time alone, altered motor performance. The performance of the Before Group was affected by the daily diazepam, and although tolerance to the impairment developed, it was incomplete. Late in the chronic administration phase (after 75 days) a toxic effect of the suspending agent became evident in all groups as a decrease in work rate, although the other performance indices were not affected. The withdrawal of diazepam from the Before Group led to improved performance which returned to the original baseline level. PMID- 2320652 TI - Possible involvement of kinins in cardiovascular changes after alcohol intake. AB - Japanese healthy male subjects were divided into two groups, i.e., a normal aldehyde dehydrogenase (ALDH) group with a low Km isozyme of ALDH for acetaldehyde, and a deficient group without it. After intake of 0.4 g/kg alcohol, the deficient group showed high levels of blood acetaldehyde, facial flushing including an increased pulse rate and a fall in diastolic blood pressure, while the normal group did not manifest these changes. In the deficient group, the total kininogen concentration gradually decreased after alcohol intake due to a reduction in low molecular weight kininogen, and plasma prekallikrein remained unchanged. The normal group showed no significant changes in any of these values after alcohol intake. In an in vitro study with pooled plasma, the low concentrations of urinary kallikrein caused a decrease in the low molecular weight kininogen only. These results suggest that kinins released by acetaldehyde induced activation of glandular kallikreins are associated with the changes in cardiovascular symptoms in deficient group which display flushing after alcohol intake. PMID- 2320653 TI - Reinforcing effects of a pentobarbital-ethanol combination relative to each drug alone. AB - The reinforcing effects of an orally delivered combination of 1 mg/ml pentobarbital plus 1% ethanol were evaluated in four rhesus monkeys. The drug combination and another liquid (either water, 1 mg/ml pentobarbital, or 1% ethanol) were concurrently available under identical fixed-ratio (FR) schedules. Substantially higher response rates were maintained by the drug combination than by any of the three other liquids. Thus, the reinforcing effects of the pentobarbital-ethanol combination were greater than those of either component drug. In a second experiment, water (the vehicle) was concurrently available with one other liquid (1 mg/ml pentobarbital, 1% ethanol, or the pentobarbital-ethanol combination). All three drug solutions functioned as reinforcers since they maintained much higher response rates than water. These results demonstrate that the greater relative reinforcing effects of the drug combination in the first experiment were not due to a lack of reinforcing effects of the 1 mg/ml pentobarbital or 1% ethanol solutions. In a final experiment, the drug combination was scheduled concurrently with 1 mg/ml pentobarbital, and FR size was systematically varied. The drug combination was then scheduled concurrently with 1% ethanol, and FR size was again varied. As FR size increased, the relative amount of responding maintained by the drug combination increased. Thus, differences in relative reinforcing effects that were evident in the first experiment were again evident in the final experiment when appropriate schedule parameter values were used. PMID- 2320654 TI - Antipanic drug treatments: failure to exhibit anxiolytic-like effects on defensive burying behavior. AB - Although the Defensive Burying paradigm has been used as a behavioral "model" for the study of anxiety and/or antianxiety agents, the effects of chronic treatment with antidepressant agents (i.e., "antipanic" agents) have not been examined in this paradigm. The present study examined the effects of two antianxiety treatments on this behavior: 1) acute treatment (30-minute pretreatment) with the benzodiazepine anxiolytic chlordiazepoxide and 2) chronic treatment (twice daily for 7-12 weeks) with the antipanic agents imipramine (IMI), desipramine (DMI) or pargyline (PARG). Prior to testing, female Sprague-Dawley rats were placed in a 40 x 30 x 40 cm Plexiglas chamber containing clay bedding material (5 cm deep) for 30-minute periods on each of four consecutive days. On the fifth day, a wire wrapped prod was placed at one end of the chamber. Rats were placed in the chamber individually and a 3 mA shock was delivered upon contact with the prod. Defensive Burying behavior (i.e., the moving of bedding material toward or over the prod) was recorded for 15 minutes postshock. In a dose-dependent manner, acute treatment with chlordiazepoxide reduced the frequency of occurrence of burying behavior, increased the latency to initiation of burying, and decreased the duration of burying. In contrast, chronic treatment with IMI, DMI, or PARG failed to exhibit anxiolytic-like effects on any measure of Defensive Burying. These data suggest that the Defensive Burying paradigm may not be an "animal model" for the study of panic disorder and potential antipanic agents. PMID- 2320655 TI - Effects of haloperidol on anorexia induced by l-norephedrine and d-amphetamine in adult rats. AB - Although amphetamine anorexia has been linked to activation of dopaminergic receptors within the lateral aspects of the hypothalamus, the receptor type by which phenylpropanolamine (PPA: the racemic mixture of d- and l-norephedrine) induces anorexia has not been identified. In the present experiment, separate groups of adult male rats were pretreated (IP) with either 0.9% saline or haloperidol (either 0.4 or 0.8 mg/kg) 45 minutes prior to treatment (IP) with either saline or 20 mg/kg l-NEP (the active enantiomer of PPA) and were then allowed 180 minutes access to food and water. Treatment with 20 mg/kg l-NEP induced comparable reductions in food intake of approximately 30% in rats pretreated with either dose of haloperidol or saline. In a sub-experiment, it was demonstrated that 1.0 mg/kg d-amphetamine sulfate reduced food intake by 25%, but this anorexic action was completely attenuated by 0.8 mg/kg haloperidol given 45 minutes prior to feeding. These results add to a growing body of literature that documents important differences between the mechanisms by which amphetamine and PPA produce their anorexic actions. PMID- 2320656 TI - Effects of perifornical hypothalamic microinjections of phenylpropanolamine and amphetamine on latency to feed and mash intake in rats. AB - To determine whether phenylpropanolamine (PPA) and amphetamine act on a common satiety mechanism, the present experiment compared the effect of unilateral microinjections (40, 80, and 160 nmol) of phenylpropanolamine hydrochloride (PPA: d,1-norephedrine) and of d-amphetamine sulfate within the perifornical hypothalamus (PFH) on consumption of a palatable sweetened-mash diet in adult male rats. Microinjection of d-amphetamine (40-160 nmol) within the PFH induced dose-dependent anorexia, whereas PPA microinjections were without effect on feeding. These results document that amphetamine and PPA do not act at a common CNS site, such as the PFH, to induce anorexia. PMID- 2320657 TI - Central action of an inhibitor of brain dopa-decarboxylase, NSD-1015, on cyanamide-induced alcohol drinking in rats. AB - A cannula for repeated intracerebroventricular (ICV) infusion was implanted stereotaxically in 16 male Sprague-Dawley rats. Subsequently, an alcohol preference test was given to each animal to establish its preferred concentration in the presence of water. After the alcohol solution was removed, 15 mg/kg cyanamide was injected subcutaneously for 4 days to maximize volitional intake of the single preferred solution of alcohol, which ranged from 7-15% in these animals. The L-aromatic amino acid decarboxylase inhibitor, NSD-1015 (3 hydroxybenzylhydrazine dihydrochloride) was then given ICV twice daily in a volume of 5.0 microliters in the following doses: 0.005, 0.01, 0.1 and 1.0 micrograms. NSD-1015 in all doses attenuated the g/kg alcohol intake of the rats; however, this decline was significant only at the lowest dose, which was pharmacologically specific, since neither food nor water intakes were altered by the treatment. Following the ICV infusions of NSD-1015, alcohol drinking returned essentially to postcyanamide levels. Further, during the interval of administration of NSD-1015, the cyanamide-induced decline in food consumption was reversed. These observations are in agreement with previous findings obtained under similar experimental conditions with the L-aromatic amino acid decarboxylase inhibitor, benserazide (Ro4-4602). They suggest that central decarboxylation or other effects of this drug on limbic system structures involved in the intake of alcohol could comprise a part of the mechanism underlying the induction of drinking. Further support is also provided for the involvement of brain dopamine and/or serotonin in the specific pattern of alcohol consumption in the rat. PMID- 2320659 TI - Tolerance and sensitization to chronic and subchronic oral caffeine: effects on wheelrunning in rats. AB - Twenty-four male Sprague-Dawley rats were tested for wheelrunning in conjunction with chronic (continuous) or subchronic (alternate day) oral caffeine administration. As expected, chronic administration led to complete tolerance to caffeine's locomotor stimulant effect, while subchronic administration produced sensitization. Results confirm earlier reports of enhanced stimulation with spaced administration of caffeine and tolerance with chronic administration. PMID- 2320658 TI - Isolate housing alters ethanol sensitivity in long-sleep and short-sleep mice. AB - Beginning at 45 days of age, male long-sleep (LS) and short-sleep (SS) mice were placed into individual cages for 21-22 days. Control animals were group-housed for the same amount of time. At 65-66 days of age, animals were given anesthetic doses of ethanol, IP. Measures taken were sleep time, body temperature at 30 and 60 minutes postinjection and blood ethanol content (BEC) at regain of righting response. Compared to the same measures in group-housed animals, sleep times and hypothermia were attenuated in isolate-housed LS and SS mice. Isolate housing resulted in a 15% increase, compared to levels observed in group-housed animals, in BEC at regain of righting in LS; there was no significant difference in BEC in SS mice. The results indicated an isolation-related decrease in sensitivity to the anesthetic effects of ethanol in LS; the effect of isolation in SS may be an increased clearance rate of ethanol. PMID- 2320660 TI - T-maze performance in rats following chronic neuroleptic treatment. AB - The effects of chronic haloperidol treatment (0.5 mg/kg/day for 21 days) on maze learning in the rat were studied. There were no differences between haloperidol- and saline-treated groups in percentage of correct responses, but the latency to respond was longer and extinction was faster in the haloperidol-treated group. We speculated that differences between both groups were due to a decrease of appetitive motivation in haloperidol-treated animals, probably caused by a decrease of dopaminergic neurotransmission. PMID- 2320661 TI - Evidence for the rewarding effects of ethanol using the conditioned place preference method. AB - Rats were tested for the rewarding effects of ethanol using a place preference conditioning procedure. After receiving a total of 15 daily conditioning trials under 1.0 g/kg ethanol (IP), a significant place preference was produced. Subjects conditioned using saline or 0.5 g/kg ethanol showed no changes in place preference. This study suggests that failures to demonstrate rewarding effects from ethanol with the conditioned place preference method may be due to an insufficient number of conditioning trials or to an inadequate exposure to the drug. The fact that place preference conditioning was effective in demonstrating ethanol reward while other methods have been equivocal suggests that this method may be a valuable technique for studying the mechanisms of ethanol reward. PMID- 2320662 TI - Chronic nicotine induces a specific appetite for sucrose in rats. AB - Thirty female albino rats were implanted with subcutaneous pellets releasing nicotine or amphetamine in order to study the effects of chronic pharmacological treatment on food intake and body weight. The pellets were removed after tolerance (a decrease in anorectic properties of the drugs) had developed. Nicotine administration produced a specific appetite for sucrose both during and following treatment (p less than 0.05). PMID- 2320663 TI - Cholecystokinin octapeptide reduces ethanol intake in food- and water-sated rats. AB - The putative satiety peptide cholecystokinin octapeptide (CCK-8) has been shown to reduce ethanol intake induced by prior fluid deprivation. Since fluid-deprived animals tend to reduce their food intake and consequently become hungry, the ability of CCK-8 to reduce ethanol intake might be limited to conditions where the motivation for food and fluid are accentuated. The present study assessed this possibility by examining the effect of peripheral injections of CCK-8 on voluntary ethanol intake fostered by the limited access procedure which uses food and water-sated rats. Under these conditions CCK-8 still produced a dose dependent decrease in ethanol intake. These results demonstrate that CCK-8 reduces ethanol intake even in the absence of hunger and thirst drives. PMID- 2320664 TI - A method for the measurement of field placement errors in digital portal images. AB - Correct placement of radiation fields relative to patient anatomy is essential in radiotherapy in order to minimise serious side effects to reduce the probability of recurrence of the tumour. One way to determine patient setup accuracy is to analyse portal images obtained in the therapy beam distal to the patient. A field placement analysis (FPA) method has been developed for detailed evaluation of patient setup by comparing positions of corresponding radiation field edges in digitised simulator and portal images. A simulator image is matched to a portal image using similar anatomical landmarks in both images and mapping these landmarks against each other applying a least squares minimisation approach. Discrepancies between the simulator field edge (reference) and a portal field edge are determined by comparing the distances between the central axis of the beam and corresponding edge segments and the angles of these segments with a reference line. Uncertainties in these distances and angles are to a large extent determined by the magnification, rotation and translation procedure. Uncertainties due to the FPA method itself are of about 1.0 mm and 0.5 degrees in portal images of head and neck fields. These FPA uncertainties are in general smaller than the variations due to patient setups. Matching of simulator and portal images of lateral pelvic fields revealed larger uncertainties: 1.7 mm and 1.1 degrees. Setup variations in this kind of pelvic radiation field are usually also larger, and therefore meaningful results can be obtained with the new FPA method. PMID- 2320665 TI - Monte Carlo calculations of scatter to primary ratios for normalisation of primary and scatter dose. AB - The separation of total absorbed dose into primary and scatter components is a commonly used technique in photon dose calculations. The primary dose component can be characterised by a measured narrow beam attenuation coefficient and a single normalisation value which establishes the relative proportion of the primary to the total dose at some reference depth and field size. The determination of this normalisation value from measured data requires an extrapolation of measured values for finite field sizes to obtain a zero field size value. We have used Monte Carlo simulations to score primary and scatter dose for photon beams of 4, 6, 10, 15 and 24 MV and report values of the scatter to primary ratio at the depth of dose maximum for the circular equivalent of a 10 cm x 10 cm field. These values have an uncertainty of less than 1% and can be used in lieu of extrapolation of measured data to establish the relative magnitude of the primary dose for a wide range of photon beam energies. PMID- 2320666 TI - Pinhole emission computed tomography: method and experimental evaluation. AB - A method for pinhole emission computed tomography (ECT) using the image processing capabilities of a gamma camera system is described and evaluated. The tomographic imaging capability of the method was assessed by studies of phantoms and its practical use by the distribution of inhaled 99Tc(m)-labelled aerosol particles in rabbits. The phantom studies demonstrate the tomographic properties in central and non-central planes. A reconstructed resolution of 4.4 mm (FWHM) and an overall homogeneity of +/-10% was obtained for a radius of rotation of the pinhole of about 8 cm. Pinhole ECT showed the distribution of inhales particles to be considerably different in two rabbits, subjected to different modes of mechanical ventilation. In planar images, on the other hand, it was difficult to appreciate the difference. PMID- 2320668 TI - Use of Gaussian beam model in predicting SAR distributions from current sheet applicators. AB - The Gaussian beam model is shown to be a good predictor of SAR distributions due to current sheet applicators (CSAs). It is fast, efficient and adaptable. SAR distributions from a single applicator and from simple arrays of CSAs in homogeneous and layered lossy media are computed at 434 and 450 MHz at CPU times of less than 60 s. The good agreement between theory and experiment justifies the use of the Gaussian beam model to predict SAR distributions from CSAs. PMID- 2320667 TI - Measurement of absorbed doses near metal and dental material interfaces irradiated by x- and gamma-ray therapy beams. AB - Soft-tissue damage adjacent to dental restorations is a deleterious side effect of radiation therapy which is associated with low-energy electron scatter from dental materials of high electron density. This study was designed to investigate the enhancement of dose to soft tissue (or water) close to high electron-density materials and to measure the detailed lateral and depth-dose profiles in soft tissue-simulating polymer adjacent to planar interfaces of several higher atomic number materials: 18-carat gold dental casting alloy; Ag-Hg dental amalgam alloy; Ni-Cr dental casting alloy; and natural human tooth structure. Interleaved stacks of calibrated thin radiochromic dosimeter films and tissue-simulating polymer were used for these measurements. Assemblies of these polymer-dosimeter stacks on both sides of the dental materials were irradiated in one fixed direction by collimated 60Co gamma-ray or 10 MV x-ray beams directed perpendicularly to the material interfaces. In another test, designed to simulate more closely therapeutic treatment conditions, a phantom constructed on both sides of a row of restored and unrestored whole teeth (restoration materials: gold alloy crown; Ni Cr alloy crown; Ag-Hg mesial-occlusal-distal (MOD) amalgam filling; unrestored tooth) was irradiated in one fixed direction by the collimated photon beams. Results indicate that the dose-enhancement in 'tissue' is as great as a factor of 2 on the backscatter side adjacent to gold and a factor of 1.2 adjacent to tooth tissue, but is insignificant on the forward-scatter side because of the predominant effect of attenuation by the high-density, high atomic-number absorbing material. PMID- 2320670 TI - An adaptive technique for digital noise suppression in on-line portal imaging. AB - Two complementary approaches to the noise suppression problem in on-line portal imaging have been analysed. Temporal filtering by image summation can substantially reduce the amount of noise in an image. In many cases, however, movements of the patient or the radiation source limit the time period over which the averaging can be done. Any remaining noise has to be dealt with by applying spatial filtering. The adaptive Lee filter is particularly suitable for portal imaging applications. It preserves a crisp definition of edges while removing noise in flat regions of the image. It can be used to obtain images of satisfactory quality with short radiation exposure of the patient. We have proposed a modification to the basic Lee technique which permits the calculation of the noise variance locally by utilising the information contained in intermediate images acquired during frame averaging. Unlike the original Lee formulation, no a priori knowledge of the noise variance is required, and in contrast to Mastin's approach (Mastin 1985), the variance may vary with position in the image. The tests of performance of the modified Lee filter, carried out using on-line images, have shown its superiority in comparison with the original Lee technique as well as with conventional averaging and median filters. PMID- 2320669 TI - Development of an automated human sperm quality system. AB - A computer-automated system, including hardware and software components, is developed for objective assessment of human sperm density and other characteristics, including morphological abnormalities and motility. The hardware component essentially consists of an IBM AT, a relatively low-cost image processing board and other inexpensive commercially available instruments. On the other hand, the software component is developed through the incorporation of image analysis, pattern recognition and modelling techniques with the knowledge of human reproduction from the available literature. The whole system is expected to produce a practical and cost-effective means for the routine assessment of human semen quality. PMID- 2320671 TI - Monte Carlo simulation of extracellular diffusion in brain tissues. PMID- 2320672 TI - Research in plastic surgical nursing. PMID- 2320673 TI - The cosmetic camouflage consultation--a holistic approach. PMID- 2320674 TI - Augmentation mammaplasty. PMID- 2320675 TI - Facelift with plication of platysma muscles. PMID- 2320677 TI - Sexually transmitted diseases. PMID- 2320676 TI - Perioperative care of the patient with diabetes mellitus. PMID- 2320678 TI - Appendix. Chlamydial infections in men. PMID- 2320679 TI - Females and males in an intake psychiatric setting. AB - It is generally acknowledged that some psychiatric disorders are more commonly found among members of one sex rather than the other (e.g., Dohrenwend and Dohrenwend 1976; Gove and Tudor 1973; Kass et al. 1983; Robins et al. 1984; Rosenfield 1980; Weissman and Klerman 1977). Females, moreover, are consistently overrepresented in treatment populations of different sorts, and various reasons involving responses to illness and inclination to seek treatment have been offered to account for this (Finkler 1984; Kessler et al. 1981; Nathanson 1975; Verbrugge and Wingard 1987). In contrast to accepted gender differences in prevalence, incidence and inclination to use services, a prevailing view about psychopathology is that the actual content or manifestations of a disorder should be "culture free" or universal. In the theory of psychopathology (e.g., implicit in DSM-III), general descriptors of the person (i.e., demographic and cultural) play a comparatively minor role in the stipulation of the manifestations of psychiatric illness. Among socially and culturally oriented psychiatrists, on the other hand, such descriptors are considered important clues to origins of psychopathology. However, in such analyces, sociocultural is usually equated with altogether different symbolic/language traditions (e.g., Finkler 1985; Lieban 1978), although reports exist of sex differences in symptom expression in Western societies (Brown and Harris 1976; Hinkle et al. 1960; Nathanson 1979). Feminist critics assert that even within the sociocultural tradition linked to Anglo American society, a bias exists with respect to how psychopathology is shaped, defined and handled (Kaplan 1983; Showalter 1985). The topic of gender differences in psychiatric morbidity is thus of considerable general interest and one that can be approached from a number of different perspectives. In this study we compare psychopathology in males and females who were referred to an intake setting. The DSM-III formulations and level and type of symptoms were the focus of analysis. The results are interpreted in light of findings in psychiatric epidemiology and social psychiatry. PMID- 2320680 TI - Family functioning, social adjustment, and recurrence of suicidality. AB - We examined suicidal and nonsuicidal patients with major depression during and subsequent to their hospitalization. Factors associated with suicidality at the index episode included psychosocial variables as well as measures of family functioning. Previous suicidality, inter-episodic adjustment, changes in family constellation, and perception of family functioning were instrumental in separating nonsuicidal patients at follow-up from patients exhibiting recurrent suicidal behavior. These results indicate that when assessing patients with major depression for suicidality, particular attention should be paid both to the social environment and to family functioning as perceived by the patient. PMID- 2320681 TI - Evaluating the capacity to work of the mentally ill. AB - This study explored the relationship between psychiatric symptomatology and the functional capacity to work. Subjects were diagnosed using DSM-III criteria and were grouped into categories of psychotic or nonpsychotic, and disabled or nondisabled, in regard to adjudication for mental impairment from the Social Security Administration (SSA). There were significant relationships between disability status and work capacity, in the direction of better performance for the nondisabled subjects. This finding reflected concordance between the evaluation procedure used in the study and the SSA's disability determination process. There was considerable overlap in work performance among subjects, however, suggesting that a functional assessment of work capacity might improve disability determination in certain cases. Results suggested that these work assessments might be as short as one or two days. PMID- 2320682 TI - Couples with an elderly parent with Alzheimer's disease: perceptions of familial relationships. AB - This study examined family relationships in families with and without an elderly parent with Alzheimer's disease. Spouses (29 pairs with an Alzheimer's diseased parent; 29 pairs with a healthy elderly parent) completed questionnaires regarding their perceived relationships with each other, their parent, and one of their own children (aged 8-18). In addition, they completed surveys that inquired about feelings of burden regarding the target parent. Couples perceived a poorer relationship with parents with Alzheimer's disease when contrasted to couples who had a healthy elderly parent. In addition, wives with an Alzheimer's parent also tended to have a more negative relationship with their husbands than wives who had a healthy parent. Perceptions of burden were associated with poorer spousal relationships for wives but not husbands. PMID- 2320683 TI - The onset of Alzheimer's disease. A longitudinal case study and a trial of new diagnostic criteria. AB - We had the opportunity to document the onset of presenile Alzheimer's disease in a female patient who presented at a very early stage and was followed for 18 months at close intervals. Disturbances of memory, of intellectual abilities, and of language were the initial symptoms, which caused significant impairment of working performance several months before becoming apparent at home. The clinically evident progression of the disease was confirmed by psychometric tests but was overlooked by cognitive screening batteries and by global severity ratings. In the absence of any signs of brain atrophy, even on repeated X-ray computed tomography, a severe temporoparietal reduction of glucose metabolism was disclosed by positron emission tomography. The typical case demonstrated several imperfections of newly introduced diagnostic criteria in their ability to identify early Alzheimer's disease. Improvements for some of these deficiencies are suggested. PMID- 2320684 TI - Some psychodynamics involved in the use of banal phrases. AB - Commonplace phrases, expressions frequent and familiar in the common vernacular, may appear so repetitively in a patient's discourse that they lose significance and so evade analytic scrutiny. These phrases are so trite and shopworn that their function as conveyors of meaning disappears. Speaker and listener quickly habituate to these expressions and automatically exclude them from consideration. Their use illustrates a process whereby a small segment of behavior becomes engorged with frozen meaning and is then maintained by the unwitting collaboration of speaker and listener, both of whom fail to recognize them as meaningful and fail to subject them to scrutiny required of the believer in psychological determinism. I will here give case illustrations of these phenomena and explore such materials for evidence of their importance and significance in the individual's psychic economy. I will compare certain of the mechanisms that support these constructs to those of other psychic phenomena, and will offer some explanation to explain their exemption from analytic scrutiny. PMID- 2320685 TI - Pregnancy and leadership: case study from an inpatient unit. AB - A psychiatrist's pregnancy creates different problems and opportunities, depending upon the professional role(s) that she occupies. In previous reports, authors have described the impact of a psychiatrist's pregnancy in private or subordinate roles such as therapist (Lax 1969; Nadelson et al. 1974), resident (Butts and Cavenar 1979), or supervisee (Baum and Herring 1975). Here I discuss additional complexities that may occur when the pregnant woman occupies a position of leadership. PMID- 2320687 TI - Twenty years on. PMID- 2320686 TI - Ego development and treatment requests. AB - Ego development theory suggests that patients might differ in the forms of psychiatric treatment they find helpful, depending on the maturity of their ego functioning. In our study, 100 adults beginning outpatient psychiatric treatment completed the Sentence Completion Test of ego development and the Patient Request Form, which measures treatment modality preference. Ego development was related to treatment requests in patterns predicted from theory: higher ego stage patients were more likely to request insight therapy, while lower stage patients were more likely to request reality checks, social intervention, and triage. We argue that the ego development construct can help treaters match patients to treatment modalities that are compatible with their frames of reference. PMID- 2320688 TI - The recollection of affect. AB - A group of psychiatric in-patients significantly over-estimated the intensity of their depression when asked to recollect how depressed they had been one week earlier. The initial level of depression affected the accuracy of recall. Unexpectedly, patients who were more depressed initially had more accurate recall, particularly for biological and symptomatically negative items of the Zung Self-Rating Depression Scale. PMID- 2320689 TI - Direct and indirect memory performance in patients with senile dementia. AB - The performance of patients with a presumptive clinical diagnosis of Senile Dementia of the Alzheimer's Type was compared to that of a group of normal elderly on several memory and neuropsychological tasks. The patients were impaired on tasks of free and cued recall, but exhibited normal performance on a word-completion procedure similar to that used by Graf et al. (1984). Reasons for the discrepancy between these findings and those from related research which reports impairment of word completion in patients with Alzheimer's Disease are discussed. Of particular interest is the role the orientating task plays in word completion performance. PMID- 2320690 TI - A comparison of anorexia nervosa and affective psychosis in young females. AB - In a retrospective case note study, 73 young females with anorexia nervosa were compared with 88 young females with affective psychosis. These groups of patients did not differ in terms of place of residence, birth order or social class. They differed very significantly, however, in terms of age at onset of symptoms, marital status, educational attainments and in the pattern of family histories of psychiatric illness. It is concluded that anorexics and young females with affective disorders are two quite distinct groups of patients. PMID- 2320691 TI - Gender, coping and psychosomatic symptoms. AB - In this study gender differences in coping were explored, using the Ways of Coping Checklist (WCC; Folkman & Lazarus, 1980). In addition, the focus was on sex differences in the predictive value of coping strategies in relation to psychosomatic symptoms. Males preferred problem-focused coping strategies, planned and rational actions, positive thinking, personal growth and humour, day dreaming and fantasies. Women preferred emotion-focused coping solutions, self blame, expression of emotions/seeking of social support, and wishful thinking/emotionality. In spite of the gender differences the results of multiple regression analyses indicated congruous relationships between coping and complaints for both sexes. Stressors and coping factors contributed in much the same way to the explained variance of symptoms and the results were generally similar for males and females. The present data also emphasize the bidirectionality of the coping-symptoms link. This holds especially for self blame, day-dreaming and fantasizing, and wishful thinking/emotionality. In contrast, distancing was found to be associated with self-reported psychosocial load. Future prospective studies should explicitly pay attention to this bidirectional relationship. PMID- 2320692 TI - Gender, social support and recovery from depressive disorders: a prospective clinical study. AB - One hundred and thirty men and women attending psychiatric hospitals with depressive disorders were interviewed at the time of their initial contact. After a mean four month interval, 119 were reassessed in order to test the hypothesis that initial levels of social support predict clinical improvement even when other potential risk factors such as age, sex, diagnosis and severity of depression are controlled. Severity and duration of the episode emerged as the only significant background predictors of recovery. The explained variance in recovery from depression due to social support was equal in men and women, and was not diminished by the background clinical predictors. According to subset analyses however, the aspects of personal relationships and perceived support that predict recovery in men and in women appear to be different. The available multiple regression models of outcome favoured a main effect of social support and provided persuasive if inconclusive evidence for a statistical interaction effect with sex. The implications for further research and for theory are discussed. PMID- 2320693 TI - The relationship between social vulnerability and the occurrence of severely threatening life events. AB - Research on the role of life events in the onset of depression has suggested that certain vulnerability factors can increase the risk of disorder in the face of a threatening event. The role of vulnerability factors to increase the likelihood of severe events occurring in the first place has remained largely unexplored. The vulnerability factor which has received the most attention is a lack of social support, particularly lack of a confiding relationship with a husband for women. A reanalysis of a number of published studies is undertaken; this shows that there is a positive relationship between lack of intimacy and the occurrence of adversity. The implications of this finding are briefly discussed, with emphasis on the need for a life-span developmental perspective in future life events research. PMID- 2320694 TI - Factors and primes: a specific numerical ability. AB - An autistic young man and a normal control were asked to factorize numbers and to recognize and generate primes. Both subjects made a similar number of errors and employed similar strategies, but they differed markedly in the speeds at which the arithmetical operations were carried out. PMID- 2320695 TI - The identification of psychiatric disorders in children who fail to attend school: a cluster analysis of a non-clinical population. AB - Interviews were conducted with parents of 100 children taken to a 'school attendance committee', because of persistent failure to attend school. Clinical assessment of the attendance problem was carried out so that children were categorized as 'school refusers' (N = 24), 'truants' (N = 53), 'both refusers and truants' (N = 9), or as 'neither' (N = 14). Any ICD-9 psychiatric disorder was separately identified. Cluster analysis of information collected in a standard way indicated that there was a group of children with the features of 'school refusal' who often had generalized neurotic disorders as well and who were mostly girls, another group with the features of 'truancy' all of whom had conduct disorders who were mainly boys, and a third cluster of children who were usually 'truants' but less often psychiatrically disturbed. The study provided evidence for the existence of school refusal with and without generalized neurotic disturbance in a non-clinical population. PMID- 2320696 TI - The validity of diagnostic systems for common mental disorders: a comparison between the ID-CATEGO and the DSM-III systems. AB - It is argued that latent trait analysis provides a way of examining the construct validity of diagnostic concepts which are used to categorize common mental illnesses. The present study adds two additional aspects of validity using multiple discriminant analysis applied to two widely used taxonomic systems. Scales of anxiety and depression derived from previous latent trait analyses are applied to individuals reaching criteria for 'caseness' on the ID-CATEGO system and the DSM-III system, both at initial diagnosis and six months later. The first multiple discriminant analysis is carried out on the initial scale scores, and the results are interpreted in terms of concurrent validity. The second analysis uses improvement scores on the two scales and relates to predictive validity. It is argued that the ID-CATEGO system provides a better classification for common mental illnesses than the DSM-III system, since it allows a better discrimination to be made between anxiety and depressive disorders. PMID- 2320697 TI - A standardized assessment of patients referred to primary care and hospital psychiatric clinics. AB - General practice based psychiatric clinics have increased in number in recent years. Case-note and case-register data examining the nature of the psychiatric disorder of the patients seen in this setting have shown contradictory findings. In this study comparison of 113 patients referred to primary care and hospital out-patient clinics is made using standardized clinical and social measures. Our results show that both groups had similar degrees of physical and social dysfunction and comparable levels of psychiatric morbidity. However, in the primary care population there were more women, and schizophreniform psychoses predominated. In the hospital sample affective illnesses and personality disorders were more common. The majority of patients preferred to consult in the primary care setting. PMID- 2320699 TI - Cortical and diencephalic lesions in Korsakoff's syndrome: a clinical and CT scan study. AB - Twenty-five male alcoholic Korsakoff patients were compared with age and sex matched non-Korsakoff chronic alcoholics and healthy volunteers on clinical and CT brain scan parameters. The scans were assessed by planimetry, visual grading procedures and computerized analysis. Reliable measures of third ventricular size were developed. The Korsakoff patients had wider third ventricles, larger lateral ventricles and wider interhemispheric fissures than the comparison groups; but sulcal and Sylvian fissure widths were equivalent in Korsakoff and non-Korsakoff alcoholics. The results suggest that, in addition to their well-established diencephalic lesions, many Korsakoff patients have sustained widespread cerebral damage. Shrinkage in the frontal brain regions appears to be especially pronounced. The implications for a dual aetiology of alcoholic Korsakoff's syndrome involving thiamine deficiency and features associated with alcoholism, probably direct alcohol neurotoxicity, are discussed. PMID- 2320698 TI - The ventricular-brain ratio (VBR) in functional psychoses: the relationship of lateral ventricular and total intracranial area. AB - CT scans were performed on 72 consecutive patients with a functional psychosis, and compared with 50 community controls. There was a specific difference in lateral ventricular area between these two groups but it accounted for only 11% of the variance in this measure. In contrast, racial and sexual differences in the ventricular-brain ratio (VBR) related to differences in intracranial area. It is argued that analysis of variance, using lateral ventricular area and intra cranial area, is more informative than VBR in examining these structural changes in functional psychoses. PMID- 2320700 TI - Psychiatric morbidity in patients with Parkinson's disease. AB - Forty patients with Parkinson's disease underwent a detailed assessment of their psychiatric state using a standardized, semi-structured interview, the Present State Examination. Analysis of the interviews yielded a profile of depressive and neurotic syndromes. Comparing the results with population norms, however, revealed that the patients were distinguished only by high levels of depressed mood and loss of interest and poor concentration. In the majority of patients the range and severity of symptoms fell below the criteria for 'caseness'. Only four patients could be allocated to an ICD-9 class, two to 'neurotic depression', one to 'anxiety state' and one to 'phobic state'. This rate was almost identical to that found in the general population. Broader indices of psychiatric morbidity were related to the patients' levels of disability and cognitive function. PMID- 2320701 TI - Obstetric complications in schizophrenia and the validity of maternal recall. AB - The significance of the excess of obstetric complications which appears to characterize the histories of schizophrenic patients is critically dependent on the validity of the source of obstetric information, especially when this is obtained by maternal recall. Twenty-one biological mothers of 17 schizophrenic and four other patients were interviewed for their recollections of individual events characterizing the pregnancy and delivery relating to each patient. These were then compared with those events documented in maternity hospital records. Only in two of the 21 instances (9.5%) were inconsistencies of detail apparent which would have affected the designation of the relevant patient as having, or as not having, experienced major obstetric complication(s). It is concluded that maternal recall can be a surprisingly accurate source of obstetric information in relation to research on schizophrenia. PMID- 2320702 TI - Perceptual and physiological dysfunction in depression. AB - P300 responses to emotive words of different hedonic tones were assessed in depressed patients (unipolar major), patients recovered from the same type of depression and normal controls. Depressed patients showed a smaller amplitude of P300 in response to negatively toned words than to positive words; normal controls showed the opposite pattern and recovered patients showed a pattern of response which resembled that of depressed patients. The experimental trials comparing responses to negative and positive stimuli in relation to neutral words showed significant differences for negative as compared with neutral stimuli, but not for positive as compared with neutral stimuli. Latencies of P300 did not differentiate depressed patients from normal controls. The results are discussed within the context of the 'expectancy' theory of information processing. PMID- 2320703 TI - Comparative fit indexes in structural models. AB - Normed and nonnormed fit indexes are frequently used as adjuncts to chi-square statistics for evaluating the fit of a structural model. A drawback of existing indexes is that they estimate no known population parameters. A new coefficient is proposed to summarize the relative reduction in the noncentrality parameters of two nested models. Two estimators of the coefficient yield new normed (CFI) and nonnormed (FI) fit indexes. CFI avoids the underestimation of fit often noted in small samples for Bentler and Bonett's (1980) normed fit index (NFI). FI is a linear function of Bentler and Bonett's non-normed fit index (NNFI) that avoids the extreme underestimation and overestimation often found in NNFI. Asymptotically, CFI, FI, NFI, and a new index developed by Bollen are equivalent measures of comparative fit, whereas NNFI measures relative fit by comparing noncentrality per degree of freedom. All of the indexes are generalized to permit use of Wald and Lagrange multiplier statistics. An example illustrates the behavior of these indexes under conditions of correct specification and misspecification. The new fit indexes perform very well at all sample sizes. PMID- 2320704 TI - Applications of covariance structure modeling in psychology: cause for concern? AB - Methods of covariance structure modeling are frequently applied in psychological research. These methods merge the logic of confirmatory factor analysis, multiple regression, and path analysis within a single data analytic framework. Among the many applications are estimation of disattenuated correlation and regression coefficients, evaluation of multitrait-multimethod matrices, and assessment of hypothesized causal structures. Shortcomings of these methods are commonly acknowledged in the mathematical literature and in textbooks. Nevertheless, serious flaws remain in many published applications. For example, it is rarely noted that the fit of a favored model is identical for a potentially large number of equivalent models. A review of the personality and social psychology literature illustrates the nature of this and other problems in reported applications of covariance structure models. PMID- 2320705 TI - Tolerance and dependence after continuous morphine infusion from osmotic pumps measured by operant responding in rats. AB - Food-deprived rats were trained to lever-press on a fixed interval 3-min schedule of food presentation. Using a cumulative dosing procedure, morphine and naltrexone were tested weekly for effects on rates of responding. A separate group of subjects was tested weekly for morphine analgesia using the tail-flick assay. Chronic morphine infusion (10 mg/kg/day, SC, from a 4-week osmotic pump) induced tolerance to the rate-decreasing and analgesic effects of morphine as demonstrated by a more than 4-fold increase in the morphine ED50s for both of these effects, relative to those of predependent rats. Physical dependence was evidenced in the operant procedure by increased sensitivity to the rate decreasing effects of the opioid antagonist, naltrexone, such that the ED50 for naltrexone was 5000 times lower than it was in predependent animals. In addition, marked weight loss was observed over the 2-h naltrexone test session. The degree of tolerance was a function of both the length of chronic administration and of the maintenance dose and was of a similar magnitude for operant responding and analgesia. Further, the degree of tolerance and dependence was comparable to that observed in other studies that used different methods of chronic drug administration. Thus, osmotic pumps provide a convenient and effective alternative for chronic drug administration in behavioral studies. PMID- 2320706 TI - Blockade of acquisition of drug-conditioned place aversion by 5HT3 antagonists. AB - The effect of two 5HT3 antagonists, ICS 205-930 and MDL 72222, on drug-induced place aversion was studied in a two-compartment apparatus with a procedure including a pre-test for spontaneous preference. Naloxone (0.8 mg/kg SC), phencyclidine (2.5 mg/kg SC) and picrotoxin (2.0 mg/kg IP) paired with the preferred compartment elicited a significant place aversion. ICS 205-930 and MDL 72222 failed to modify spontaneous place preference when paired with both compartments. ICS 205-930 (30 micrograms/kg SC) paired with the preferred and, in other experiments, with the non-preferred compartment, also failed to modify spontaneous preference. ICS 205-930 (7.5, 15 and 30 micrograms/kg SC), paired with both compartments, dose-dependently reduced the place aversion induced by naloxone (0.8 mg/kg SC), phencyclidine (2.5 mg/kg SC) and picrotoxin (2.0 mg/kg IP). MDL 72222 (30 micrograms/kg SC) paired with both compartments had a similar effect. The result indicate that 5HT, via 5HT3 receptors, plays a role in the aversive properties of drug stimuli. PMID- 2320707 TI - Behavioral effects after intrathecal administration of cholinergic receptor agonists in the rat. AB - Behavioral effects of nicotine and cytisine, and the cholinesterase inhibitors physostigmine and 9-amino-1,2,3,4-tetrahydroacridine (THA), administered intrathecally (IT) at the lumbar level in the rat have been evaluated. Antinociceptive dose relationships were established using the tail immersion test. Total activity, locomotion and rearing were also measured in computerized test boxes. The nicotinic receptor antagonist, mecamylamine, and the muscarinic receptor antagonist, atropine, were used to study the selectivity of the effects. Physostigmine and THA significantly decreased total activity, locomotion and rearing as compared to control animals. The motor effects of physostigmine were completely antagonized only partly. Mecamylamine had no antagonistic effect. Nicotine did not affect any activity parameter. Cytisin reduced total activity and locomotion 1-6 min after dose. IT physostigmine, 15 micrograms, increased tail immersion latency for 30 min. No significant increase in response latency in this test was observed after the IT administration of nicotine or THA, whereas cytisine elicited a small increase. The IT administration of THA, nicotine and cytisine was also associated with gnawing, vocalization and hyperactivity and in the case of THA, diarrhoea. These effects were blocked by mecamylamine. Physostigmine antinociception as well as the behavioral effects including total activity, locomotion and rearing caused by physostigmine and by THA are most probably due to an action on spinal muscarinic receptors. Nicotinic receptors do not seem to be involved in spinal antinociception. Some aversive behavioral effects caused by the IT administration of nicotinic receptor agonists could, however, be attenuated by the spinal administration of the antagonist mecamylamine, which may indicate the involvement of nicotinic receptors in afferent sensory transmission. PMID- 2320708 TI - Alprazolam in the elderly: pharmacokinetics and pharmacodynamics during multiple dosing. AB - Previous studies have suggested that elderly men eliminate alprazolam more slowly than young adults. This study in the elderly was designed to determine whether a change in pharmacokinetics influences the response to alprazolam during multiple dose regimens. In addition, the study was designed to determine alprazolam pharmacokinetics and the degree to which its hydroxymetabolites accumulate, the degree of psychomotor impairment, and whether tolerance to impairment and sedation develops during three different multiple dose regimens. Twenty-six subjects completed this study. The subjects were randomized into one of three treatment groups: 0.25 mg q8h, 0.5 mg q8h, and 2 mg q12h. Subjects remained in the clinic for 8 days (day -2-day 5). Day 0 was used as a drug free testing day to establish baseline scores for sedation, digit symbol substitution (DSS), card sorting (CS) tasks, and two computer tests. Subjects received the drug according to schedule on days 1 through 4, with day 5 as the washout day. Blood samples were assayed for alprazolam, alpha-hydroxyalprazolam and 4-hydroxyalprazolam. Alpha-hydroxyalprazolam concentrations were below assay detection limits in all subjects in the 0.25 and 0.5 mg q8h groups and less than or equal to 2.6 ng/ml in the 2 mg q12h group. When detectable, 4-hydroxyalprazolam concentrations were less than 10% of the corresponding alprazolam concentration. Mean alprazolam oral clearance values in the three treatment groups ranged between 0.54 and 0.62 ml/min/kg and half-lives were in excess of 21 h. Degree of sedation and impairment was dose related. Sedation and impairment was not higher on day 4 despite concentrations 2-3 times as great as on day 1, indicating development of tolerance. Subjects were not, however, back to baseline level of performance on day 4. PMID- 2320709 TI - Conditioned taste aversion and place preference with buspirone and gepirone. AB - The effects of the nonbenzodiazepine anxiolytics buspirone and gepirone were compared to diazepam at 1, 3, and 10 mg/kg using the conditioned taste aversion (CTA) paradigm. Buspirone and gepirone produced stronger CTA than diazepam (3 and 10 mg/kg) across repeated conditioning trials, indicating that these nonbenzodiazepine anxiolytics may have stronger aversive properties than diazepam. The effects of buspirone and gepirone (1 and 3 mg/kg) were also assessed using the conditioned place preference (CPP) paradigm. Both buspirone (1 and 3 mg/kg) and gepirone (3 mg/kg only) produced CPP, indicating that these drugs may have rewarding properties, and that buspirone is more potent than gepirone in producing CPP. These findings demonstrate that buspirone and gepirone have affective properties similar to abused drugs, and may therefore have abuse potential. It was also demonstrated that buspirone (3 mg/kg), but not gepirone (3 mg/kg), increased dopamine (DA) synthesis in the nucleus accumbens, a mesolimbic brain area thought to be involved in drug reward. PMID- 2320710 TI - Assessment of working memory in rats using spatial alternation behavior with variable retention intervals: effects of fixed-ratio size and scopolamine. AB - The effects of fixed-ratio (FR) size, scopolamine, and the interactions between FR size and scopolamine were investigated in male F344 rats on working memory as assessed by spatial alternation behavior maintained under FR schedules of food presentation where the interval between trials was varied among values of 2, 4, 8, 16, and 32 s within each session. The magnitude of the FR size on the correct and incorrect levers was varied systematically from 1 response to 2, 4, 8, or 16 responses in order to determine whether the FR size influenced either the percentage of correct responding, rates of responding, or both. Under the primary baseline condition, that is when the FR size on both the correct and incorrect levers was one response (designated FR1 FR1), the percentage of correct responses decreased with increasing retention interval duration. Increasing the FR size on the correct lever produced FR-dependent increases in the percentage of correct responding as well as in rates of responding. Increasing the FR size on the incorrect lever produced FR-dependent decreases in correct responding, but had little effect on rates of responding. Dose-effect curves for scopolamine were determined on performance maintained under FR values on the correct and incorrect levers, respectively, of FR1 FR1, FR1 FR10, FR10 FR1, and FR10 FR10. In general, scopolamine produced dose-related decreases in the percentage of correct responding, although the magnitude of the effects of scopolamine varied not only with dose, but also with the length of the retention interval and with changes in FR size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2320711 TI - DSP-4-induced depletion of brain norepinephrine produces opposite effects on exploratory behavior 3 and 14 days after treatment. AB - Exploratory behavior of a complex novel environment was examined 3 and 14 days following treatment with the noradrenergic-selective neurotoxin, DSP-4. This toxin significantly decreased norepinephrine concentrations in neocortex and hippocampus but not hypothalamus. DSP-4 significantly increased exploratory behavior in animals tested 3 days after treatment. In contrast, exploratory behavior was decreased in animals tested 14 days after treatment. The effect of DSP-4 at 3 days is similar to treatments that act to inhibit noradrenergic function such as administration of the alpha 1-antagonist, prazosin, or the alpha 2-agonist, clonidine. The effect of DSP-4 at 14 days resembles that observed following treatment with the alpha 1-agonist, phenylephrine, or the alpha 2 antagonist, idazoxan. These data provide additional support for a role of noradrenergic systems in exploratory behavior. The simplest explanation for the time dependent effects of DSP-4 on exploratory behavior is the occurrence of the slow development of a supersensitivity of cerebral systems affected by norepinephrine. PMID- 2320712 TI - Influence of dose and route of administration on the kinetics of fluoxetine and its metabolite norfluoxetine in the rat. AB - Fluoxetine (FL) is being used in neuropharmacology as a tool for studying various functional roles of serotoninergic neurons. Its kinetics was studied in rats, a species widely used in neurochemical studies, after IV (2.5-10 mg/kg) and oral (5 20 mg/kg) administration. When injected IV the drug followed apparent first-order kinetics up the 10 mg/kg dose. Its volume of distribution was large and total body clearance was relatively high compared to liver blood flow. The mean elimination half-lives (t1/2) of FL and its active metabolite norfluoxetine (NFL) were about 5 and 15 h, respectively. The mean blood:plasma concentration ratios of FL and NFL approached unity and plasma protein binding was 85-90% for both compounds. After oral doses the kinetics of FL were complex. At the lowest dose tested (5 mg/kg) the drug was efficiently extracted by the liver (extraction ratio about 60%), resulting in bioavailability of only about 38%. Plasma areas under the curve (AUC) of the metabolite were approximately the same as after IV injection of the same dose; consequently the metabolite-to-parent drug ratio after oral administration (about 5) was approximately twice that after IV injection of FL (about 2.5). At higher doses, however, the oral bioavailability (e.g. Cmax and AUC) appeared greater than expected, possibly because of transient saturation of FL first-pass metabolism in the case of the 10 mg/kg dose and concomitant saturation of elimination kinetics at the higher dose (20 mg/kg). The apparent elimination t1/2 of FL markedly increased and the metabolite-to-parent drug ratio declined with the higher dose, this also being consistent with saturable elimination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2320713 TI - A comparison of the effects of scopolamine and diazepam on acquisition and retention of inhibitory avoidance in mice. AB - Administration of either the muscarinic antagonist scopolamine or the benzodiazepine diazepam prior to training produced a dose-dependent impairment in the retention of one-trial inhibitory avoidance training in mice. To investigate the nature of this drug effect, the effects of scopolamine and diazepam were subsequently assessed on both acquisition and retention of inhibitory avoidance using a multiple-trial, training-to-criterion procedure. The training was conducted using either continuous trials in which the mouse was free to shuttle back and forth between shock and safe compartments or discrete trials in which the mouse was moved from the shock compartment of the safe compartment at the start of each trial. In either case, training continued until the mouse refrained from crossing into the shock compartment for a specified length of time on a single trial. Scopolamine (1.0 mg/kg) administered before training significantly increased the number of trials required to attain criterion, but did not affect retention when these mice were tested 2, 16, or 28 days later. In contrast, diazepam (1.0 mg/kg) did not significantly alter the number of trials necessary to reach criterion, but impaired retention of the inhibitory response in mice trained using discrete trials. The differences in the amnestic effects of scopolamine and diazepam revealed by this detailed analysis suggest that diazepam does not impair inhibitory avoidance performance through an effect on cholinergic function. PMID- 2320714 TI - Competition for sucrose-pellets in triads of male Wistar rats: effects of acute and subchronic chlordiazepoxide. AB - Within triads of male Wistar rats, some animals almost completely abstain from competition for palatable sucrose pellets (so-called poor-performing rats), whereas other rats consistently win the competition (so-called high-performing rats). Subchronic (5 mg/kg; 5 consecutive days), but not acute (0.1-20 mg/kg), treatment with chlordiazepoxide temporarily helped poor-performing rats to behave more competitively. This finding, considered together with parallel studies (using high-performing rats), suggested that chlordiazepoxide's beneficial effect was only demonstrable when the poor-performing rats had become tolerant to the drug's initial sedative effect. PMID- 2320715 TI - Effects of nicotine gum on psychomotor performance in smokers and non-smokers. AB - Two experiments were conducted to investigate the effects of nicotine on human performance. In the first study six smokers, who had been allowed to smoke normally prior to testing, completed a battery of psychometric tests (choice reaction time, memory scanning, tracking and flicker fusion threshold) at set points over 4 h after chewing 0, 2, or 4 mg nicotine polacrilex gum. A second study followed a similar design, but used five non-smoker volunteers who were required to chew only the 0 or 2 mg nicotine gum. Blood nicotine levels following the gum were measured in all subjects. The results indicate that additional nicotine improved both the speed and accuracy of motor activity among the smokers, but did not enhance central cognitive processes. No drug effects were found in the non-smoker study. PMID- 2320716 TI - Behavioral evidence implicating dopamine in sensorimotor arousal and norepinephrine in the sedative effects of antidepressant drugs. AB - The effects of acute and chronic antidepressant treatment on acoustic startle were evaluated in three experiments. Administration of 2.5-10.0 mg/kg desipramine, amitriptyline, and nortriptyline depressed acoustic startle responding after repeated sensory stimulation. In contrast to the tricyclic drugs, the serotonin reuptake inhibitor zimelidine increased acoustic startle, and inhibition of dopamine reuptake following acute nomifensine and bupropion administration did not influence startle reactivity in the doses examined. The response reducing effects of desipramine and amitriptyline persisted following chronic exposure to these drugs, and these findings were discussed in relation to the inhibitory actions of the tricyclics on locus coeruleus neurons. A second major finding in this study was that animals challenged with d-amphetamine during desipramine and amitriptyline withdrawal showed a facilitated startle response. Enhanced startle reactivity to amphetamine was also observed following long-term exposure to iprindole, and a withdrawal hyperactivity of acoustic startle was evident after chronic treatment with amoxapine, bupropion, and nomifensine. These results agree with evidence that repeated administration of antidepressants increases dopamine neurotransmission which modulates sensorimotor arousal. PMID- 2320717 TI - Gangliosides enhance the anti-immobility response elicited by several antidepressant treatments in mice. AB - Ganglioside pretreatment enhanced the anti-immobility effect induced in the forced swim test after a chronic treatment with desipramine, mianserin, clomipramine, nialamide or repeated electroconvulsive shock in mice. Gangliosides, which had no effect per se, showed a clear dose-response relationship in enhancing the anti-immobility effect of desipramine. These results suggest that, regardless of their mechanisms of action, gangliosides facilitate the behavioral response of several antidepressant treatments. PMID- 2320718 TI - Congenital malformations, stillbirths, and early mortality among the children of atomic bomb survivors: a reanalysis. AB - Of all the data sets pertinent to the estimation of the genetic risks to humans following exposure to ionizing radiation, potentially the most informative is that composed of the cohort of children born to atomic bomb survivors. We present here an analysis of the relationship between parental exposure history and untoward pregnancy outcomes within this cohort, using to the fullest extent possible the recently revised estimates of the doses received by their parents, the so-called DS86 doses. Available for study are 70,073 terminations, but DS86 doses have not been or presently cannot be computed on the parents of 14,770. The frequency of untoward pregnancy outcomes, defined as a pregnancy terminating in a child with a major congenital malformation, and/or stillborn, and/or dying in the first 14 days of life, increases with combined (summed) parental dose, albeit not significantly so. Under a standard linear model, when the sample of observations is restricted to those children whose parents have been assigned the newly established DS86 doses (n = 55,303), ignoring concomitant sources of variation and assuming a neutron RBE of 20, the estimated increase per sievert in the predicted frequency of untoward outcomes is 0.00354 (+/- 0.00343). After adjustment for concomitant sources of variation, the estimated increase per sievert in the proportion of such births is 0.00422 (+/- 0.00342) if the neutron RBE is assumed to be 20. A "one-hit" model with appropriate adjustments for extraneous sources of variation results in an almost identical value, namely, 0.00412 (+/- 0.00364). When the sample is extended to include parents lacking the full array of dose parameters necessary to calculate the DS86 dose, but sufficient for an empirical conversion of the previously employed T65DR dose system to its DS86 equivalent, we find under the linear model that the estimated increase per sievert in untoward pregnancy outcomes is some 31% higher than that published previously, 0.00264 (+/- 0.00277), assuming an RBE of 20, after adjustment for extraneous sources of variation. (Since a dose could not be calculated in 367 of the 70,073 outcomes, the n = 69,706). The corresponding value with the one-hit model is 0.00262 (+/- 0.00294). PMID- 2320719 TI - Differential effects of chronic ingestion of tritiated water on prenatal brain development. AB - Female rats were given tritiated drinking water (3 microCi/ml) from 30 days before mating up to and throughout pregnancy. At this low dose, the course and the outcome of pregnancy were normal. The differences between newborn body and cerebral weights of the treated rats and those of control animals were on the borderline of significance. In contrast, cerebral DNA and cerebral protein were highly significantly lower. In 30-35% of the treated population the DNA and protein values were more than 2 standard deviations (SD) below the mean values for the control population. Thus the number of the progeny of the mothers exposed to tritiated water that were considered to have "outstandingly low" levels of DNA and protein was 14-17 times greater than in the control group. The irradiated population also had 3-5% of severely affected individuals with cerebral DNA and protein values more than 2 SD below the mean of the experimental population. However, even in this irradiated population, a certain number of individuals did not show the effects of radiation as indicated by DNA and protein values that were not lower than the mean values of the control population. These animals may represent those individuals in which normal (control) populations would have cerebral DNA and protein levels well above the average (by 1 to 2 SD), but here, because of prenatal irradiation, were about average. If so, this lack of effect of irradiation cannot be caused by protection against radiation. However, at present, a differential repair mechanism of protection in those animals (or their mothers) that showed little or no effect of irradiation cannot be excluded. PMID- 2320721 TI - Comparison of stochastic and deterministic methods for modeling spur kinetics. AB - Stochastic and deterministic kinetic methods have been used to model the temporal evolution of spatially nonhomogeneous clusters of reactants resulting from the dissociation of one to six water molecules into either H3O+, OH, and e-aq, or H atoms and OH radicals. When the ionic fragmentation initially producing H3O+, OH, and e-aq is considered, the stochastic and deterministic methods predict similar time dependences for the decay of the reactive species; however, the two methods suggest very different product yields. For a two-dissociation spur, the deterministic treatment overestimates both the H2 and the H2O2 yields by about 70%. The error decreases to less than 15% for a spur with six water dissociations. For a distribution of spurs representing a high-energy electron track, the differences in the predicted yields of reactants are less than 6% at 0.1 microseconds, but the stochastic and deterministic predictions for the yields of H2 and H2O2 differ by about 50%. The kinetics of spurs produced by the fragmentation of water to H atom and OH radical shows discrepancies in both the reactant and the product yields. The size of the discrepancy decreases as the number of H/OH pairs increases, and the predictions of the two techniques are almost the same for clusters of six water dissociations. PMID- 2320720 TI - On the measurement of DNA double-strand breaks by neutral elution. PMID- 2320722 TI - Use of calcium channel antagonists as magnetoprotective agents. AB - Human polymorphonuclear leukocytes (PMNs) exhibited a time-dependent (0 to 60 min) increase in the release of lysozyme and lactate dehydrogenase (degranulation) when exposed to a static (direct current) magnetic field of 0.1 Tesla. When 1 X 10(6) PMNs were treated with the calcium channel antagonists diltiazem, nifedipine, and verapamil before exposure to a magnetic field, no significant change in degranulation was detected compared to control and sham exposed PMNs that were similarly treated. Likewise, magnetic field-induced inhibition of cell migration was prevented with the addition of these antagonists. Such changes in degranulation and cell migration occurred in a dose dependent manner. These results indicated that these agents protected PMNs exposed to a magnetic field, and the damage to the cells that is mediated by magnetic field-stimulated Ca2+ influx might be preventable. In this regard, pharmaceutical agents might prove useful in protection against injurious electromagnetic field exposure. PMID- 2320723 TI - The relationship between radiosensitivity and repair of potentially lethal damage in human tumor cell lines with implications for radioresponsiveness. AB - The relationship between intrinsic radiosensitivity and repair capacity was studied for 22 human tumor cell lines in vitro. The experimental material was taken from 19 published papers. Parameters from three radiobiological models were used to assess this relationship: the one-hit multitarget model (D0 and n), the linear-quadratic model (alpha and beta), and the mean inactivation dose (D). Data were obtained for cells in three stages: exponentially growing cells (exp), plateau-phase cells plated immediately after irradiation (ip), and plateau-phase cells plated after completion of PLD repair (dp). No significant difference was found between radiosensitivity of exp and ip cells. There was no correlation between repair capacity and intrinsic radiosensitivity assessed with plateau phase cells plated immediately after irradiation. The correlation studies between intrinsic radiosensitivity or repair capacity and clinical responsiveness were achieved by assigning cell lines to one of three groups of decreasing in vivo radioresponsiveness: highly, medium, and poorly responsive. There was a significant correlation between radiosensitivity and radioresponsiveness, but no correlation between repair capacity and radioresponsiveness. The average repair capacity was about 0.6 Gy, in terms of D. Three parameters, the mean inactivation dose of exponentially growing cells, of plateau-phase cells plated immediately after irradiation, and of plateau-phase cells plated after completion of PLD repair, could be used equally to assess the relationship between in vitro data and radioresponsiveness. The present results are compared to those obtained in a similar study on a group of 48 nontransformed fibroblast cell strains. PMID- 2320724 TI - Differential repair of potentially lethal damage in exponentially growing and quiescent 9L cells. AB - The alteration of potentially lethal damage repair by postirradiation treatment with hypertonic saline (0.5 M PBS) was investigated in exponentially growing and quiescent 9L cells in vitro. A single dose of X rays (8.5 Gy) immediately followed by a 30-min treatment with hypertonic PBS at 37 degrees C reduced the survival of exponentially growing 9L cells by a factor of 13-18 compared to survival of irradiated immediately and delayed-plated cells, while the survival of quiescent cells was reduced by only a factor of 5-8. Survival curves confirmed the relative resistance of the quiescent 9L cells versus exponentially growing 9L cells to X rays plus hypertonic treatment. Both the slope and the shoulder of the survival curve were reduced to a greater extent in exponentially growing cells than in the quiescent cells by hypertonic treatment. The response of quiescent cells cannot be explained by either the duration of hypertonic treatment or the redistribution of the cells into G1 phase. We show that quiescent 9L cells can recover from hypertonically induced potentially lethal damage when incubated under conditions which have been found to delay progression through the cell cycle, and postulate that an altered chromatin structure or an enhanced repair capacity of quiescent 9L cells may be responsible for their resistance. PMID- 2320725 TI - Expression of transfected recombinant oncogenes increases radiation resistance of clonal hematopoietic and fibroblast cell lines selectively at clinical low dose rate. AB - To determine the effect of oncogene expression on gamma radiation sensitivity of hematopoietic compared to fibroblastic cells, we selected clonal sublines of an interleukin-3 (IL-3)-dependent hematopoietic progenitor cell line 32D cl 3 and NIH/3T3 embryo fibroblastic cells following transfection with each oncogene linked to the mycophenolic acid resistance gene. Each mycophenolic acid-resistant subclone demonstrated high levels of specific poly(A)+ mRNA for each oncogene. The parent line 32D cl 3 demonstrated similar radiosensitivity at 116 cGy/min (D0 126, n 1.17) compared to 5 cGy/min (D0 123, n 1.65). This pattern was not altered in subclones of 32D cl 3 cells transfected with the epidermal growth factor (EGF) receptor gene and grown in EGF (at 116 cGy/min D0 104, n 0.998, at 5 cGy/min D0 115, n 1.09), or in 32D cl 3 cells expressing the v-sis oncogene (at 116 cGy/min D0 122.4, n 1.79, at 5 cGy/min D0 135, n 1.43). In contrast, expression of the transfected oncogenes v-erb-B, v-abl, or v-src conferred significant radioresistance at 5 cGy/min dose rate (D0 194, n 1.77; D0 165.5, n 1.56; D0 171, n 1.28, respectively). With the exception of v-sis, oncogene expression resulted in nonautocrine factor independence of 32D cl 3 subclones, and production of donor origin tumors in syngeneic new-born or adult mice. Two rare spontaneous factor-independent subclones of 32D cl 3 were also tested. Nonautocrine clone 32D cl 2 demonstrated significantly increased radioresistance at low dose rate (D0 186, n 1.63), while autocrine (IL-3 producing) subclone 32D cl 4 revealed no significant increase in radioresistance at 5 cGy/min. The parent fibroblast cell line NIH/3T3 showed an intrinsic relative radioresistance at low dose rate (at 5 cGy/min D0 157.3, n 1.81, compared to 116 cGy/min D0 134.3, n 1.57). Expression in NIH/3T3 of transfected oncogenes v-abl, v-fms, v-fos, or H-ras increased radioresistance at low dose rate (D0 208.6, n 1.61; D0 206.6, n 1.51; D0 167.5, n 1.85; and D0 206.8, n 1.08, respectively). Thus expression of each of several oncogenes induces resistance to gamma irradiation at 5 cGy/min in hematopoietic and fibroblast cell lines. These data may help explain the clinical recurrence of oncogene-expressing leukemia and lymphoma cells after marrow stem cell ablative doses of low-dose-rate total-body irradiation. PMID- 2320726 TI - Effects of a second heating on blood flow in tumors. AB - The blood flow in RIF-1 tumors of C3H mice, as measured with the 86Rb uptake method, declined markedly after a single heating at 43.5 degrees C or 44.5 degrees C for 1 h. However, preheating at 42.5 degrees C for 1 h significantly lessened the decrease in tumor blood flow caused by subsequent heating at 43.5 degrees C or 44.5 degrees C for 1 h. Such an influence of preheating on the effect of reheating in decreasing the tumor blood flow was significant as early as 6 h after the preheating, peaked at 36 h, and then decayed the following 2-3 days. In fact, a reheating at 43.5 degrees C for 1 h applied 36 h after a preheating at 42.5 degrees C for 1 h resulted in an increase rather than a decrease in blood flow. The cause of such a profound impact of preheating on the effect of reheating on the blood flow is unclear. However, circumstantial evidence including the histopathological appearance of tumors suggests that thermotolerance is induced in the blood vessels of the tumor as a result of preheating. PMID- 2320727 TI - Induction of hypoxia in glass versus Permanox petri dishes. AB - The survival of Chinese hamster ovary cells in culture following graded doses of X rays delivered under aerobic and hypoxic conditions, or treatment with the bioreductive drug SR 4233 under hypoxic conditions, was evaluated as a function of whether cells were plated onto glass or Permanox plastic petri dishes. In the case of treatment with SR 4233, the influence of varying the total volume of medium in the dishes was also studied. While the Permanox petri dishes were sufficient to yield "radiobiological" hypoxia, that is, oxygen enhancement ratios of approximately 3.0 were obtained for X irradiation, they were inferior to glass petri dishes with respect to the hypoxia-selective cytotoxicity of SR 4233. For a 90-min hypoxic exposure to 40 microM SR 4233, the surviving fraction of cells plated on plastic dishes averaged about 50-fold higher than that of cells plated on glass dishes. Although varying the total medium volume did affect the extent of SR 4233-induced cytotoxicity for glass dishes--drug toxicity decreased slightly with increasing medium volume--this was not the case for the plastic dishes, in which the cell survival following a fixed SR 4233 exposure was essentially constant as a function of medium volume. These results suggest, at least for SR 4233, and under these experimental conditions, that Permanox petri dishes are not satisfactory for such studies. PMID- 2320729 TI - [Misinterpretation of the adhesio interthalamica and the commissura epithalamica (posterior) in occlusive hydrocephalus in the computed tomogram]. AB - As a cause of an occlusive hydrocephalus, sometimes by CT a cystic malformation of the third ventricle is falsely assumed. This misinterpretation is based on the enlargement of the ventricular system, which leads to an unusual visualization of the interthalamic adhesion and the epithalamic (posterior) commissure. We show these structures to be the reason for the misleading diagnosis by comparing anatomical sections, ventriculography and magnetic resonance imaging (MR) with each other. Finally we discuss the clinical significance by presenting cases, in which an operative treatment of the so called "cyst" already had been planned. For the definite diagnosis we favor MR. PMID- 2320728 TI - Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay. AB - A method for measuring DNA damage to individual cells, based on the technique of microelectrophoresis, was described by Ostling and Johanson in 1984 (Biochem. Biophys. Res. Commun. 123, 291-298). Cells embedded in agarose are lysed, subjected briefly to an electric field, stained with a fluorescent DNA-binding stain, and viewed using a fluorescence microscope. Broken DNA migrates farther in the electric field, and the cell then resembles a "comet" with a brightly fluorescent head and a tail region which increases as damage increases. We have used video image analysis to define appropriate "features" of the comet as a measure of DNA damage, and have quantified damage and repair by ionizing radiation. The assay was optimized for lysing solution, lysing time, electrophoresis time, and propidium iodide concentration using Chinese hamster V79 cells. To assess heterogeneity of response of normal versus malignant cells, damage to both tumor cells and normal cells within mouse SCC-VII tumors was assessed. Tumor cells were separated from macrophages using a cell-sorting method based on differential binding of FITC-conjugated goat anti-mouse IgG. The "tail moment", the product of the amount of DNA in the tail and the mean distance of migration in the tail, was the most informative feature of the comet image. Tumor and normal cells showed significant heterogeneity in damage produced by ionizing radiation, although the average amount of damage increased linearly with dose (0 15 Gy) and suggested similar net radiosensitivities for the two cell types. Similarly, DNA repair rate was not significantly different for tumor and normal cells, and most of the cells had repaired the damage by 30 min following exposure to 15 Gy. The heterogeneity in response did not appear to be a result of differences in response through the cell cycle. PMID- 2320730 TI - [A solitary metastasis in the trapezium bone]. AB - Carpal bone is an uncommon location for metastases, and diagnostic problems can occur when a solitary metastasis mimics acute arthritis or osteomyelitis clinically as well as radiologically. PMID- 2320732 TI - [The reduction lens--an important but neglected radiologic aid]. PMID- 2320731 TI - [Functional analysis of the cervical spine in healthy persons]. AB - Radiograms were taken of subjects with no symptoms of cervical spine problems; the cervical spine was evaluated in the spontaneous posture and at maximal flexion and extension. The position and movement of the vertebra, intervertebral height and gliding were calculated. The results showed that (1) lordosis in women occurred less pronounced than in men, and that there was an increase with age; (2) C 2-3 was the least flexible segment and motility increased in the caudal direction; mobility decreased with age and the segments of the lower cervical spine with the highest mobility decreased the most; (3) all posterior and ventral intervertebral heights showed a decrease with age at C 5-6 and C 6-7; (4) vertebral gliding decreased with age. PMID- 2320733 TI - [Atypical pneumonia?]. PMID- 2320734 TI - Nurses plea for "cash deposit waiver" denied: suicide. PMID- 2320735 TI - Rx: avoid "speculation" & "admissions" in charting. Case in point: Brookover v. Mary Hitchcock Mem. Hosp. (893 F. 2d 411-NH (1990)). PMID- 2320736 TI - Legal case briefs for nurses. GA.: police blood sample: nurse-patient duty? WA.: nurse bars admission of psych. pt.: suicide. PMID- 2320737 TI - "Fraudulent concealment": suit delayed twelve years. Case in point: Chapman v. Primary Children's Hosp. (784 P. 2d 1181--UT (1989)). PMID- 2320738 TI - Nurse fights school med. policy: free speech. PMID- 2320739 TI - Anesthesiologist fails to communicate with CRNA. Case in point: Franklin v. Gupta (567 A. 2d 524--MD (199-)). PMID- 2320740 TI - Delay in detecting esophageal tear: death. Case in point: Phillips v. Eastern Maine Med. Center (565 A. 2d 3-6--ME (1989)). PMID- 2320741 TI - Preclinical evaluation of pions in vivo: experience at TRIUMF. AB - This paper describes the results obtained from in vivo studies of the pion beam at the TRI University Meson Facility (TRIUMF). The studies encompass work (from 1978 to 1986), designed to evaluate the RBE for early and late effects and to assess the importance of X-ray dose rate and treatment volume on these values. Results with early responding tissues, i.e. mouse and pig skin and mouse intestine indicate a pion RBE of about 1.5 in the clinically relevant dose per fraction range of 2-3 Gy. At these doses, RBE appears to be independent of the reference X-ray dose rate. However, at high doses per fraction, the RBE values become increasingly X-ray dose rate dependent. The induction of late effects by pions has been assessed by monitoring the late dermal response of pig skin; late fibrosis was not assessed in this study. The values obtained using the chosen endpoint indicate that the RBE is not significantly higher than that seen in any of the early responding tissues for pion doses as low as 2-3 Gy per fraction. The effect of increasing the treatment volume for pion therapy has been assessed using mouse intestine. The results show that for a constant field size, RBE decreases with increasing peak width. However, if peak width is held constant and field size increased, there is evidence for an increased RBE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2320742 TI - Diagnosis and treatment of malignant pheochromocytoma with 131I-meta iodobenzylguanidine: a case report. AB - The case of a 67-year-old male patient with metastatic malignant pheochromocytoma is described to illustrate the significant improvement of the diagnosis and treatment of pheochromocytoma since the recent introduction of 131I-meta iodobenzylguanidine (131I-MIBG). Because of the generally observed tumor heterogeneity as to 131I-MIBG uptake and radiosensitivity in advanced disease, treatment results may be improved further, if 131I-MIBG therapy is initiated when tumor load is still small. PMID- 2320743 TI - The clinical behavior of radiation-induced thyroid cancer in patients with prior Hodgkin's disease. AB - Second primary neoplasms are occurring with increasing frequency. Despite growing literature on the incidence and etiology of this phenomenon, very little has been documented about the clinical aspects and biological behavior of these tumors. As our experience has hinted at a worse prognosis for second primaries, we thought it of interest to study this phenomenon for one type of tumor. We reviewed 32 cases of thyroid cancer arising as a second neoplasm in patients with Hodgkin's disease and compared various clinical characteristics to reported series of de novo (non-radiation-induced) thyroid cancer. Thyroid cancer, as a second primary, occurred more frequently in males with a more malignant histology and was diagnosed at a more advanced stage. The survival appears to be worse. The behavior of radiation-induced thyroid cancer in a host with prior malignant neoplasia appears to be more aggressive than that of both de novo (non-radiation induced) thyroid cancer and radiation-induced thyroid cancer in a host with no prior malignancy. The selected nature of the cases precludes any firm conclusions. This type of information should be collected prospectively for all secondary malignancies as it may have an impact on the clinical management of these patients. PMID- 2320744 TI - Endometrial carcinoma: a comparative analysis of the therapeutic results and causes of failure after treatment by radiation combined with surgery or radiation therapy alone. AB - At the present time endometrial carcinoma is considered to be among the most frequent of gynecological tumors and its incidence is now reaching that of cervix carcinoma. In this paper, we present the results of two series of treatment for endometrial carcinoma, one using the combination of surgery and radiation, the second one using radiation treatment alone. Indeed, due to our recruitment criteria between 1968 and 1978 at the Montpellier Cancer Institute, the proportion of patients treated exclusively by physical agents was more or less equal to those receiving combined treatment. In many cases, either because of the poor condition of the patient, or due to local involvement, irradiation alone was used. The report of the results explain the therapeutic failures and show by means of two sequential series how techniques have been developed. Previously treated patients were excluded (44 cases). PMID- 2320745 TI - Arterial occlusive disease after radiotherapy: a report of fourteen cases. AB - Fourteen cases of arterial occlusion or severe narrowing following radiotherapy are studied in order to assess the possible etiological role of such therapy in arterial lesion. Surgical results are also discussed in terms of long-term efficacy. The average time of occurrence after radiotherapy was 8 years post radiotherapy. This series includes 7 supra-aortic trunk stenoses and 7 abdominal aorta trunk stenoses. The doses received in the volumes irradiated ranged from 47 to 70 Gy with standard fractionation. Association of atherosclerotic risk factors (smoking, hyperlipidemia, diabetes, high blood pressure) was present in 12 patients, but stenoses were usually confined to irradiated areas, and at times occurred in uncommon sites. Surgical management included 11 by-passes, 2 endarterectomies and one percutaneous transluminal angioplasty. All patients experienced immediate and satisfactory functional improvements. Three patients were re-operated on because of the re-occlusion of the by-pass (2 cases) and graft infection (1 case). On the whole, stenoses in previously irradiated areas showed no particular difficulties for surgical treatment. It was concluded that radiotherapy seems to be a definite risk factor for arterial occlusion or narrowing, especially in association with atherosclerotic risk factors. PMID- 2320746 TI - Quality assurance in radiotherapy by in vivo dosimetry. 1. Entrance dose measurements, a reliable procedure. AB - Entrance dose measurements were performed with semiconductor detectors on patients treated for head and neck and brain tumors with a 6 MV X-ray beam. A total number of 554 treatment set-ups were measured. The results showed a gaussian distribution with a mean value of 97.8% and a standard deviation of 2.8%. A systematic error of 2.2% on the mean value was shown to be due to a systematic deficiency in the algorithm used in the planning system and to a systematic error in the application of the dosimetry protocol. Two treatment techniques were identified leading to an erroneous dose delivery. Finally, large deviations (more than 2 S.D.) of the measured dose from the expected dose were detected in 3% of the measured treatment set-ups, the sources of the errors could in all cases be identified and eliminated in the further treatment sessions. This study demonstrated the reliability of the use of semiconductor detectors for in vivo dosimetry and its usefulness as part of a departmental quality assurance program. PMID- 2320747 TI - Blood flow and blood volume in a transplanted rat fibrosarcoma: comparison with various normal tissues. AB - Blood flow measurements following i.v. infusion of iodo-antipyrine labelled with 14C(14C-IAP) and blood volume measurements following i.v. injection of 125I human serum albumin and 51Cr-labelled red blood cells were made in a transplanted rat fibrosarcoma for comparison with various normal tissues. The tumour-blood partition co-efficient for 14C-IAP was found to be 0.79 +/- 0.07 which is similar to most of the normal tissues studied. The solubility of 14C-IAP in plasma was found to be higher than that in whole blood. Blood flow to tumours less than 1000 mm3 was found to be 17.9 +/- 4.0 ml blood 100 g tissue-1.min-1. These values were considered to be primarily measurements of nutritive flow. Blood in the tumours was found to occupy around 1% of the tissue space which was similar to that found for normal muscle and skin. There was no direct correlation between % blood volume and blood flow for the different tissues studied. The haematocrit of blood contained in tumour tissue was calculated to be significantly lower than that of blood contained in the normal tissues. It was suspected that permeability of tumour blood vessel walls to 125I-HSA could have accounted for this difference. PMID- 2320748 TI - Dose-time considerations of head and neck squamous cell carcinomas treated with irradiation. AB - The dose-time factors in the external beam treatment of 473 patients with squamous cell carcinoma of the pharyngeal wall, vocal cord, pyriform sinus or supraglottic larynx were considered. The effect of overall treatment time on the tumor response was quantified by estimating the increment in dose per day needed to achieve a constant rate of local control, that is, the dose required to counterbalance the effect of growth of the tumor during irradiation. The estimated increment in isoeffect dose per day varies between sites, however, the increments, although estimated with considerable uncertainty, are in general larger than 1 Gy per day. These estimates are consistent with accelerated tumor clonogen repopulation during irradiation. PMID- 2320749 TI - Conjunctival intraepithelial and invasive squamous cell carcinomas treated with strontium-90. AB - Twenty-seven patients with malignant epithelial tumors of the conjunctiva were treated between 1967 and 1987. Histological diagnosis was intraepithelial epithelioma in 15 cases (56%) and squamous cell carcinoma in 12 (44%). All patients were treated with a strontium-90 source on cup-shaped applicators of different sizes according to the extension of the tumor. Surface dose ranged from 60 Gy in a single treatment to 140 Gy in 7 fractions, depending on the thickness of the lesion. Fifteen patients were previously untreated, 7 were irradiated after some type of surgical treatment and 5 were treated for recurrence after multiple surgical excisions. Follow-up period ranged from 2 to 15 years. No patient died of his tumor. There were four local recurrences, three of them in patients with intraepithelial carcinoma. Two of the recurrences were salvaged with a new beta-ray treatment and the other two with enucleation. Since 1981, standard policy was to irradiate the entire conjunctiva in patients with diagnosis of intraepithelial epithelioma. Five patients developed cataracts. Considering the high primary control rate and minimal morbidity, strontium irradiation should be considered as a first-choice treatment for conjunctival tumors. PMID- 2320750 TI - Neurological damage in patients irradiated twice on the spinal cord: a morphologic and electrophysiological study. AB - We reviewed the files of 950 patients treated for Hodgkin's disease since 1966 and were able to find five patients treated with radiochemotherapy and irradiated twice on volumes including a cord segment, at various time intervals, and surviving until now. Seven patients with comparable clinical and therapeutic features, but not reirradiated on the cord, were chosen as a control group and were examined with the same diagnostic procedures. The cumulative cord dose in the reirradiated patients was recalculated and ranged from 50 to 70 Gy. All these patients and the control cases were followed up for more than 10 years and presented no or only minor neurological symptoms. We compare the results of both magnetic resonance imaging (MRI) and electrophysiological studies (spinal and scalp recorded somatosensory evoked potentials--SEPs) in an attempt to define the characteristics of the subclinical damage present in these patients. While no cord abnormality was demonstrated with MRI, electrophysiological studies evidenced a clear difference between cases and controls, as far as the D10-P1 conduction time and SEPs average amplitude are concerned. Advantages and drawbacks of a wider use of electrophysiological methods in research work on cord radiation damage are presented, along with the possible implications of the results obtained for the understanding of the pathogenesis and of the dose dependence of radiation myelitis (RM). PMID- 2320751 TI - Radiosurgery and the double logistic product formula. AB - The double logistic product formula is proposed as a method for predicting the probability of developing brain necrosis after high dose irradiation of small target volumes as used in stereotactic radiosurgery. Dose-response data observed for the production of localized radiation necrosis for treating intractable pain with the original Leksell gamma unit were used to choose the best fitting parameters for the double logistic product formula. This model can be used with either exponential or linear quadratic formulas to account for the effects of dose, fractionation and time in addition to volume. Dose-response predictions for stereotactic radiosurgery with different sized collimators are presented. PMID- 2320752 TI - Computer-aided construction and quantitative evaluation of missing-tissue compensators. AB - We have implemented a system for the design and construction of missing-tissue compensators for Radiation Therapy. The patient topography is obtained by Moire' photography. The thickness of lead required to compensate for a given amount of missing tissue was determined experimentally for three photo-beam energies and a combination of field sizes and geometries. With the aid of a computer, tissue deficit information is converted to isolead-thickness lines. These are used as input to a computer-controlled milling machine to fabricate the compensator. The effectiveness of compensation was evaluated in phantom and in vivo. This work describes the initial effort required to implement a program for compensation of tissue deficit at the patient's surface. It also introduces tools for assessing quantitatively the degree of dose uniformity which can be achieved using compensators in clinical applications. PMID- 2320753 TI - Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses. AB - Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered. PMID- 2320755 TI - What if I were the respondent? PMID- 2320754 TI - Specification of dose in neutron therapy. PMID- 2320756 TI - Relationship of hope, coping styles, concurrent losses, and setting to grief resolution in the elderly widow(er). AB - This descriptive study was based on Dimond's Bereavement Adaptation Model; investigation was made of the relationship between hope, concurrent losses, coping style, setting (hospital, hospice, nursing home), and grief resolution. Seventy-five elderly persons who had been widowed 12-18 months completed the Herth Hope Scale, the Jalowiec Coping Scale, and the Grief Resolution Index by mail. A significant positive relationship was found between effective grief resolution and a high hope level; 0-1 concurrent losses; the use of confrontive, optimistic, palliative, supportant, and self-reliant coping styles; and the death of the spouse within a hospice setting. The importance of the type of setting, hope level, and specific coping styles on grief resolution in the elderly widow(er) is suggested by the findings. PMID- 2320757 TI - Supplemental-information-seeking behavior of cardiovascular nurses. AB - The Krikelas model was used as a framework for investigating supplemental information-seeking behavior of cardiovascular nurses. (Supplemental information is that which is not available from memory and could be made available by computer). One hundred seventy-five instances of supplemental-information-seeking behavior were collected from 46 cardiovascular nurses in three metropolitan hospitals. Self-report and observation-interview methods were used. Findings indicated that the nurses sought patient-specific data most frequently, followed by institution-specific data and domain knowledge. They needed a surprisingly large portion of the information to track people, equipment, medications, and reports. The findings have implications for nursing information system design. PMID- 2320758 TI - The holistic paradigm in nursing: the diffusion of an innovation. AB - Nursing today is affected by challenges to the beliefs and values underlying the delivery of health care services. Results of a bibliometric analysis of the nursing literature since 1966 revealed a process of paradigm change in which a scientific medical model is being replaced by a model based on the concept of holism. Key ideas representing a holistic paradigm of health appear with increasing frequency in the journals of the nursing field, demonstrating the diffusion of a new and different perspective in the practice of nursing. PMID- 2320759 TI - Position modifies carotid artery blood flow velocity during straining. AB - The Valsalva maneuver (VM) produces rapid shifts in cerebrovascular blood flow and is often implicated in aneurysm rupture and rebleeding. To determine whether intensity of hemodynamic shifts is affected by position, we examined effects of five body positions (chair, 70 degrees and 30 degrees upright, flat, side) on carotid artery blood flow velocity (CABFV) across the VM in 141 healthy adults (30-55 yrs.). Subjects strained at 40 mmHg pressure for 10 seconds. CABFV was measured continuously by ultrasonic Doppler technique. During straining, position significantly (F = 13.7; p less than .0001) affected CABFV. Less reduction occurred in the chair (p less than .05) position than in any of the others. The 70 degrees position produced less fall in CABFV (p less than .05) than did the 30 degrees, flat and side positions. Less increase in CABFV across the VM was recorded in the chair position (p less than .05) than in any of the others. It is concluded that the chair position can be used therapeutically to reduce severe shifts of CABFV associated with straining. PMID- 2320760 TI - Responses of elderly spouse caregivers. AB - In this paper three categories of variables were identified to predict spouses' reactions to caregiving roles: patient characteristics, the caregiving environment, and characteristics of the caregiver. Measures of these variables were administered to 159 spouse caregivers. Four domains of caregivers' responses were identified: negative emotional reactions, feelings of responsibility for the patient, feelings of abandonment by family, and impact of caregiving on daily schedules. These domains were influenced most by patient negative behaviors, physical health, and age, and by caregiver age, employment, and emotional status. Amount of assistance, affective support, and hours of care also were predictive of spouse responses. PMID- 2320762 TI - Perceived health status, self-esteem and body image in women with rheumatoid arthritis or systemic lupus erythematosus. AB - A cross-sectional, descriptive, comparative design was used with a sample of 26 women with rheumatoid arthritis (RA), 23 women with systemic lupus erythematosus (SLE), and 28 healthy (HLT) women to examine: (a) the relationship of illness to perceived health status, self-esteem and body image, (b) the relationships between perceived health status and both self-esteem and body image, (c) the relationship between these three variables and age and time since diagnosis, and (d) the problems, needs and fears of women with RA and SLE. Perceived health status differences were found between the ill and healthy subjects, but self esteem differences were nonsignificant; mean scores on body image of RA and HLT groups approximated each other, while SLE subjects had lower scores. Perceived health status was directly related to self-esteem, but not to body image. Age and time since diagnosis were weakly positively related to perceived health status. Both similarities and differences were identified in the problems, needs and fears of RA and SLE subjects. PMID- 2320761 TI - Depression and anxiety among chronically ill heart patients: age differences in risk and predictors. AB - Anxiety and depression for 399 survivors of a 1,102-member heart disease cohort were assessed 8 to 9 years post-hospitalization. Approximately one-third reported symptoms of emotional distress and one-fourth were on anti-anxiety drugs. Predictors of anxiety and depression were analyzed through logistic regression. Subjects age 65 and over were less likely than younger patients to report anxiety or depression and also reported less heart-associated disability, the strongest predictor of distress for both age groups. Other significant predictors included a previous history of distress, low income, female sex, and beta blocker use. PMID- 2320763 TI - [The baroreflex pathway and essential arterial hypertension]. AB - The function of every baroreflex nervous pathway, and the influence of a diuretic treatment, were investigated in a group of 26 patients with essential hypertension and 24 normals measuring their blood pressures and R-R intervals while at rest and during the Valsalva manoeuvre, deep breathing at 6 breaths/min, standing up from a lying position, handgrip, and psychic stress. Eight hypertensive subjects were studied before and after the diuretic suppression. The precocious R-R and systolic responses to the standing up were smaller in hypertensive patients that in normals, and this decreased when the degree of hypertension augmented. Both anomalies persisted in patients with diuretics treatment and normal blood pressures. All this suggest smaller velocity or later initiation of the cardiac orthosympathetic response. PMID- 2320764 TI - [Survey of the attitude of primary care physicians towards AIDS]. AB - A representative group of primary care physicians from Areas 4 and 5 of the Institut Catala de la Salut were surveyed in orden to know their opinion about the spreading of HIV infection, the value of serological tests and the methods to prevent the infection of health care providers. More than half of the physicians (58.5%) had never been in contact with an HIV infected patient. Of the surveyed physicians, 47.2% believe that it is necessary to spread out more information on preventive measures amongst health professionals. 48.4% believe that confidentiality is important but only 16.9% consider it is important to obtain an informed consent to perform serological testing and another 22.5% mainly trust systematic serological testing. Primary care can play an important role avoiding the spread of HIV infection and, in fact, the importance of preventive measures and confidentiality are assumed by an elevated percentage of health professionals. The usefulness of serological testing, however, is not properly assessed valued and little importance is granted to the patient's consent for their performance. PMID- 2320765 TI - [Pathologic fracture of the sternum in a patient with anorexia nervosa]. AB - It has been observed that anorexia nervosa (AN) patients present osteoporosis (OP) although the mechanism by which it occurs is not well known. The reduction in calcium intake as well as a decrease in estrogen production which is associated with involutive OP, could be involved. We have found in the literature 16 cases of AN and OP, one of which presented a fracture of the sternum. We now present another case of fracture of the sternum. This implies a high incidence of this type of fracture in OP due to AN which is extremely rare in involutive OP, which suggests that the ethiopathogenic factors of the former are different from those of the latter. PMID- 2320766 TI - [Hypereosinophilic syndrome and acute ventricular failure]. AB - Hypereosinophilic syndromes are characterized by very high levels of eosinophils in peripheral blood and a dysfunction of several organs as a consequence of their massive infiltration by eosinophilic cells. Cardiac alterations are traditionally known as fibroplastic endomyocarditis (Loeffler's Syndrome). We present the case of a female patient admitted in another center for the study of an accidentally discovered eosinophilia and referred to us because of her progressive hemodynamic deterioration followed by a poor clinical evolution. The anatomopathologic findings showed the classical injuries of this Syndrome; specially at cardiac level, where it is important to highlight the occupation of all the right ventricule's cavity by a clog. These injuries justified the origin of the stormy clinical presentation. PMID- 2320767 TI - [Evolution of the number of authors in clinical and basic science journals in the Spanish language]. AB - The number of signing authors in Revista Clinica Espanola. Revista Espanola de Fisiologia and Revista Espanola de Oncologia have been analyzed from their first to the last received issue. The results obtained show an increasing number of authors in all journals specially during the 70s. The results also point out a relative decrease in the number of authors in basic sciences in relation to clinical publications. The increase in the number of authors in The Revista Espanola de Oncologia has started somewhat later than the others. The environmental and professional stress as well as the interrelations between different hospital members have been suggested, amongst others, as the possible cause of these events. PMID- 2320768 TI - [Laminar atelectasis in an adult with episodes of dyspnea and hemoptysis]. PMID- 2320769 TI - [Paraneoplastic eosinophilia: hypereosinophilic syndrome and disseminated carcinoma]. PMID- 2320770 TI - [Myasthenic syndrome induced by clozapine]. PMID- 2320771 TI - [Cerebral hemorrhage caused by cocaine consumption]. PMID- 2320772 TI - [Endobronchial involvement as a symptom of tuberculosis in AIDS]. PMID- 2320773 TI - [Microangiopathic hemolytic anemia associated with breast cancer]. PMID- 2320774 TI - [Provocation test using metaraminol in a case of familial Mediterranean fever]. PMID- 2320775 TI - [Monitoring progress towards health for all in the European region of WHO IV. Changes in health systems]. AB - This review deals with recent changes in health services development and support among the Member States of the European Region in response to changes in health indicators in the framework of the Regional targets for Health for all. Developments in research, in health legislation and in training which take into account the targets of Health for all represent long-term actions; several countries mention efforts to increase community participation in the development and evaluation of health programmes, efforts which must be actively pursued. Changes are perforce slow, and economic pressure represents both a challenge and a constraint. PMID- 2320776 TI - The influence of reproductive and hormonal factors on thyroid cancer in women. AB - We conducted a study on 165 women with thyroid cancer and 214 hospital controls in order to investigate the role of reproductive and hormonal factors in the aetiology of thyroid cancer. Late age at menarche (Relative risk (RR) for menarche at greater than or equal to 14 vs less than or equal to 11 = 2.8), menstrual irregularity (RR = 1.7), late age at first birth (RR for first birth at greater than or equal to 28 vs less than or equal to 21 = 2.4) and at last birth (RR for last birth greater than or equal to 30 vs less than 30 = 2.2) significantly increased the risk of the development of thyroid cancer both in premenopausal and postmenopausal women. Parity was, in the present study rather inconsistently related to disease status whereas voluntary abortions and miscarriages were completely unrelated. A non significant increasing risk was observed with age at menopause older than 50, and with the use of oral contraceptives in premenopausal women. The mechanism of action of female hormones on the thyroid gland remains largely obscure, but the observation that age at first and, perhaps, subsequent pregnancies may be relevant points to an interplay of reproductive factors (and, possibly, their hormonal correlates) more complex than previously suggested. PMID- 2320777 TI - [Monitoring progress towards health for all in the European region of WHO. III. Life style and physical environment]. AB - A review of recent progress towards the Regional targets set for Health for all in the European Region of WHO, as regards lifestyle and environmental factors. Tobacco consumption (in most countries), and alcohol drinking (mainly in countries with previous high consumption) show some improvement. Illicit drug use is emerging in new countries, although it appears to stabilise in previously affected areas. Despite considerable efforts on environmental factors, there remains a serious problem of communication with the public, and action is poorly coordinated; indicators for environmental health show little progress. PMID- 2320778 TI - Trends surface models applied to the analysis of geographical variations in cancer mortality. AB - To discuss different trends of the geographical distribution of cancer mortality, progressively more complex surface models were fitted to cancer death certification data in the 95 Italian provinces for the period 1975-77, using trend surface analysis. This method is based on fitting first to sixth order regression equations, where dependent variables are latitude and longitude, and the independent one is the standardized mortality ratio (SMR) for various cancer sites. The procedure was implemented using the SYMAP package and appropriate routines ad hoc developed. General patterns in geography of cancer in Italy were therefore identified (such as the marked North/South gradient in mortality from most sites), thus helping in discerning main underlying pictures and permitting identification of local abnormalities (positive or negative residuals, corresponding to high or low mortality areas), which are often obscured by more general patterns using standard methods of analysis. Results and maps are presented and discussed in detail with reference to total mortality and three major sites (lung and intestines in males and female breast) for which regression surfaces with satisfactory fitting were identified. Some of the positive residuals (i.e. those for lung and breast cancer in women in urban concentrations of Central and Southern Italy) were already known, and explainable in terms of available knowledge of the causes of the neoplasms, chiefly smoking and reproductive habits in the past. Other findings, such as the consistent area of positive residuals in a chiefly rural area around the mouth of the river Po, offer useful suggestions for further aetiological research. PMID- 2320779 TI - [Human salmonellosis and turtles in France]. AB - Two immunosuppressed children were infected with Salmonella, due to turtles living in water. So we investigated the carriage of Salmonella among those animals. Among the 95 investigated animals, 10 were carrying Salmonella (Arizonae, Rissen, Pomona and Blockley). The water of 6 containers out of 20 contained Salmonella. Comparing our data to others in the litterature, we conclude that human salmonellosis, acquired from turtles are not, by now, a major problem in France. Nevertheless, a number of those animals are carrying Salmonella. So an epidemiological survey is necessary, and immunosuppressed patients should avoid contact with those animals. PMID- 2320780 TI - [Smoking by general practitioners in Maine-et-Loire]. PMID- 2320781 TI - [Assessment of medical activity and quality of health care at French hospitals]. PMID- 2320782 TI - [The in vivo penetration of erythromycin into alveolar macrophages]. AB - In order to appreciate the in vivo penetration of erythromycin the alveolar spaces a broncho-alveolar lavage was carried out in 24 guinea pigs, 30 minutes, 1 hour 30 minutes and three hours after a single intraperitoneal injection of 50 mgms. of erythromycin. The erythromycin dose was assessed by a microbiological method in the alveolar macrophages and the supernatant of the broncho-alveolar lavage liquid. The intramacrophage concentrations of erythromycin were 3.9, 11.5 and 12 times higher than the serum concentrations at 30 minutes, 1 hour 30 and three hours respectively. The concentrations in the broncho-alveolar lavage liquid was always higher than the serum concentrations tacking account of the different dilutions estimated with relation to the glucose concentrations. At 30 minutes, 1 hour 30 minutes and three hours the alveolar macrophages contained 1.9; 7.6 and 6 times more erythromycin respectively than the lavage supernatant. From the first half hour of its administration the erythromycin was concentrated in the alveolar spaces, in particular within the macrophages. Already noted in vitro, this rapidity of erythromycin concentration in vivo in alveolar macrophages appears to be one of the reasons to explain its activity against micro-organisms developing within macrophages. PMID- 2320783 TI - [Effect of nebulized salbutamol in 26 patients hospitalized for asthma attack]. AB - Twenty-six asthmatic patients who were hospitalised following an acute asthmatic attack and who had a peak expiratory flow of less than 50% predicted, without hypercapnia, received 5 mg. of salbutamol delivered by a micronebulizer LSA on admission (HO). At H1, 10 mg of additional salbutamol were nebulised in cases where there had been an increase of less than 20% of the PEF. At H2, all the subjects received steroid therapy. Group 1 in which success was defined by an increase of 20% of peak flow judged at H1 and H2, and group II where the increase in peak flow was less than 20%. Group II benefited at H2 by treatment with theophylline or salbutamol intravenously given in a randomised fashion. At H8 the 2 treatments were associated in group II in cases of failures. 15 men, and 11 women aged 40 +/- 17 suffering from severe asthma (65% of Charpin Stage IV) were included. The mean peak flow at HO was 32 +/- 9% of the predicted PEF. 21 subjects, or 81% improved their peak flow by more than 20% at H2. The toleration for salbutamol was very good from the cardiovascular point of view. At HO there was no clinical criteria nor peak flow assessment which would enable one to predict the failures from nebulized salbutamol for a given subject. Nevertheless a level of dyspnoea of greater than 5 on Borg's scale and a peak flow of less than 150 l/min made failure likely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2320784 TI - [Pleural symphysis with tetracyclines for pneumothorax. The value of thoracic peridural analgesia]. AB - The aim of this study was to assess the value of peridural thoracic analgesia (ATP) to prevent pain observed during pleural symphysis with tetracycline (STP) for pneumothorax (PNO). 12 patients (age 27 +/- 6 years) having a spontaneous PNO benefited from 13 SPT (1 gm, tetracycline diluted in 60 cc of normal saline) under cover of an APT (at the D5-D6 level) with Fentanyl (0.1 mg) and Bupivacaine 0.5% adrenalin (1 mg/kg). The protocol was used on three successive days. Repeated determinations of blood bupivacaine levels were performed in 9 patients on the first day. No patient had an intolerable pain which required injection of parenteral morphine and/or an interruption of the protocol. For two patients (one of them having a right symphysis and then a left symphysis one month later) the treatment sessions to achieve a symphysis were totally painless. 10 patients experienced moderate pain, mainly on the first day, which was relieved by reinjection of peridural bupivacaine (25 mg) (n = 9) or by the parenteral injection of non morphine analgesia (n = 1). No patient had a respiratory depression, collapse or bradycardia. The blood bupivacaine levels were always significantly less than the toxic levels (1.6 mg). The results observed suggest that APT, (Fentanyl and Bupivacaine) is an effective method, non toxic and well tolerated for the prevention of intolerable pain which is seen in SPT for PNO. PMID- 2320785 TI - [Isolated alveolar hypoventilation as a tubercular sequellae]. AB - Whilst the sequelae of extensive tuberculous infections generally manifest as an overall respiratory failure, characterised by a rise in the alveolar arterial gradient for oxygen and often CO2 retention, we report some observations on six patients with significant pleural and parenchymal tuberculosis; these patients presented with a restrictive syndrome associated with an apparently isolated alveolar hypoventilation. In four of these patients an effort test showed that there was adequate adaptation to alveolar ventilation on effort. In one patient measurement of PO.1 in a resting state and then during the course of a test of CO2 responsiveness revealed an absence of any response to CO2. On the basis of these results, we propose that in certain subjects suffering from significant sequelae of tuberculous disease the major functional abnormalities can be expressed as alveolar hypoventilation. This latter is not necessarily followed by a mechanical overload leading to an eventual fatigue of respiratory muscles but rather to a disorder of the regulation of ventilation. The basic mechanism of such an anomaly remains undetermined. PMID- 2320786 TI - [Sleep apnea syndromes and Arnold-Chiari malformation]. AB - The Arnold-Chiari malformation (MAC), ectopic medulla of the cerebral hemispheres, may be the basis of respiratory problems provoked by compression of the respiratory centre. It is associated with numerous respiratory problems in children; there are however few publications related to the association of MAC and ventilatory problems in adults. It was recently suggested and subsequently shown that the syndrome of sleep apnoea (SAS) could occur in relation to MAC. We report a new observation documenting the association of MAC and SAS. The surgical cure of MAC enabling a remission of SAS suggests the existence in this case of a causal relation between the two pathologies. A search for such a malformation by imagery of the occipito-medullary crest should be a part of the work up in SAS when the cause remains undetermined. PMID- 2320787 TI - [Endobronchial tuberculosis simulating cancer]. AB - Endobronchial tuberculosis may simulate a bronchial neoplasm. It is the data from a bronchial biopsy carried out along with the X-ray and endoscopy examination followed by the bacteriology of the expectorating sputum which enables a diagnosis to be made. This form of diagnosis is known but is rare. The clinical outcome is very good after specific treatment, although the radiological signs and above all the endoscopic findings improve more slowly. PMID- 2320788 TI - [Alveolar proteinosis in a facade plasterer. A sequential study of bronchoalveolar lavage and thoracic computerized tomography]. AB - Alveolar proteinosis is a rare disease. We report a case occurring in a patient who smoked and was a facade plasterer who was treated with repeated pulmonary lavage. A mineral analysis of the lavage fluid recovered a significant amount of silica and iron oxide confirming the massive exposure of the patient to these minerals. The favourable outcome over the next 7 years was associated as regards respiratory function, with a progressive improvement in lung volumes and pulmonary output and of CO diffusion capacity, as regards broncho-alveolar lavage there was a regular increase in the cellularity and finally as regards CT scanning (at high resolution) there was a progressive clearing of the alveolar opacities only leaving the persistent opacities in the interstitium. PMID- 2320789 TI - [Aspergillus colonization of a pulmonary sequestration. Apropos of a case associated with erythema nodosum]. AB - We describe a case of interlobar pulmonary sequestration diagnosed at thoracotomy in which there were a number of unusual features at presentation: an opacity with multiple cavities, positive aspergillus precipitins, erythema nodosum and a haemothorax complicating a trans-thoracic needle biopsy. Although it is unusual to find such a constellation of symptoms and signs they could be explained in a logical fashion. PMID- 2320790 TI - [Pleural effusion induced by bromocriptine]. AB - Bromocriptine, a derivative of ergot of rye, is used in high doses for the treatment of Parkinson's disease and may be responsible for pleuro-pulmonary complications. We report a case of a 72 year old patient treated for 2 years for Parkinson's disease with a daily dose of 30 mgms. of bromocriptine and in whom a pleural effusion, initially unilateral then bilateral, was discovered with a deterioration in the general physical state. The effusion was a transudate and examination did not give any clues as to aetiology, there was a rapidly favourable outcome following the cessation of treatment. Amongst the respiratory complications of bromocriptine it is the pleuro-pulmonary fibrosis which is most frequently reported. The cases of isolated pleural effusions are rare and are generally exudates. Several hypotheses have been put forward to explain the pathogenesis of these disorders: there is a theory that the molecule induces a toxic fibrogenesis, there is a vascular theory analogous with the secondary effects of methysergide and finally immunological theory. The frequency of the disorder is probably underestimated and these drug reactions justify a close follow up for any respiratory problems in patients who are subjected to treatment with bromocriptine. PMID- 2320791 TI - [Primary pulmonary choriocarcinoma]. AB - The authors report a case of a young woman who had been found to have a chorio carcinoma in the apex of the left lower lobe, following a major and recurrent haemothorax. A study of her past history and a gynaecological examination had not revealed any evidence of a primary tumour. Following this observation the possibility of a primary pulmonary carcinoma was considered and also the usual aetiological hypothesis, namely the migration of trophoblastic cells during an abortion even followed by a normal pregnancy and a degeneration after several years of these cells blocked in the pulmonary capillaries. PMID- 2320792 TI - Stubby prostheses in the rehabilitation of infants and small children with bilateral lower limb deficiencies. AB - Stubby prostheses have been used in the habilitation of very small children with bilateral lower limb deficiencies, particularly bilateral above knee limb deficiencies. While we reported on "The Use of Stubbies For the Child with Bilateral Lower Limb Deficiencies" in 1973, the literature has very little except in relation to the geriatric amputee. We have continued since 1973 to use stubbies in the bilateral above knee limb deficient child, as well as in the child with an above knee/below knee combination, with great success in establishing early balance, followed within several months by the application of articulated prostheses with equal success in establishing independent walking without the use of crutches or walkers. PMID- 2320793 TI - [Dyspnea and hypoxemia]. PMID- 2320794 TI - [Doppler echocardiographic evaluation of regurgitation of valves]. PMID- 2320795 TI - [Primary lung cancer presenting as a solitary thin-wall cavity]. PMID- 2320796 TI - [Clinical evaluation of coronary artery fistula and coronary artery-cardiac chamber shunt]. AB - Coronary artery fistula and coronary artery-cardiac chamber shunts were observed in 16 cases out of 462 consecutive cases in which coronary angiography was performed. 9 of these cases had coronary artery fistula, 5 of the cases had coronary artery-cardiac chamber shunts. 2 cases had both of these conditions. Coronary artery fistula has a draining vein originating from the coronary artery and an entering vein terminating in the cardiac chamber or the pulmonary artery. Coronary artery-cardiac chamber shunts have no such veins, and contrast material used in the injection phase of coronary angiography escapes directly into the cardiac chamber. 2 cases of coronary artery fistula, 2 cases of coronary artery cardiac chamber shunts, and 1 case involving the both of these conditions showed positive results in submaximal exercise tolerance tests, and no significant arteriosclerotic changes in the coronary artery. These factors lead us to suggest that coronary artery-cardiac chamber shunts cause cardiac ischemia for the same reason that coronary artery fistula does. PMID- 2320797 TI - [A case of elderly (83-year-old) woman with possible left atrial myxoma]. AB - A 78-year-old woman with exertional dyspnea (Hugh-Jones Grade III) and dry cough was admitted to our hospital in April, 1983. She had marked cardiac cachexia and a loss of body weight due to long term heart failure. On physical examination a systolic ejection murmur and a diastolic rumbling murmur were heard without the opening snap sound. Chest radiography revealed pleural effusion and cardiomegaly. M-mode and two dimensional echocardiography demonstrated abnormal echoes in the left atrium, the density being 22.7 Hounsfield Unit. Radionuclide angiography and magnetic resonance imaging (MRI) provided similar findings. No other mass lesion existed in the other chambers. Based on these findings, the mass was diagnosed as a left atrial myxoma. She has been well except for periodic congestive heart failure, for about five years since her discharge. The course of her ailment is interesting because her treatment is mainly symptomatic. PMID- 2320798 TI - [An autopsied case of juvenile myocarditis which showed a remarkable cardiac enlargement during the course of six months]. AB - A 19-year-old student was admitted for orthopnea. He had been a badminton player having no experience of serious diseases until he became aware of exertional epigastralgia ten days before admission. On examination, blood pressure was 102/70 mmHg, heart rate 148, and respiration 34. A third sound and moist rales were heard. The liver was enlarged and palpable at 8 cm below the right costal margin. The titers of the virus neutralizing antibodies determined on admission were all less than 32-fold. Chest roentgenogram as compared with that taken six months before admission showed a marked increase in the cardiothoracic ratio and pulmonary venous congestion. Echocardiogram showed a markedly dilated cavity of the left ventricule (LV) (LV diastolic diameter = 74 mm) compared with the cavity of the right ventricule (RV) (RV diastolic diameter = 20 mm) and diffusely impaired wall motion of the LV (fractional shortening = 9%). He died of intractable congestive heart failure two weeks after admission. Heart weight was 620 g. The LV cavity was markedly dilated, but the thickness of the LV free wall was within normal limits. Microscopy of the both atria, the RV, and the basal ventricular septum showed acute and chronic-staged inflammation. However, microscopy of the free wall of the LV showed only slight interstitial fibrosis without necrosis of the myocytes. The marked dilatation of the LV cavity would be due to either the same mechanism as that of dilated cardiomyopathy or excessive exercise after infection with myocarditis. This case showed that LV dilatation without myocardial necrosis/degeneration could develop among patients with myocarditis. PMID- 2320799 TI - [Ethmoiditis and its orbital complications in children]. AB - In order to evaluate the clinical evolution of ethmoiditis with orbital complications in children and the frequency of surgical treatment, the authors reviewed the clinical findings, evolution, complications and treatment on 74 children with acute ethmoiditis. The antibiotics heal the majority of children (69 cases) until the stage of periorbital cellulitis. The abscesses which are more frequent in older children require surgical drainage. PMID- 2320800 TI - Lethal anuria complicating high dose ifosfamide chemotherapy in a breast cancer patient with an impaired renal function. AB - A sixty-year-old woman with advanced breast cancer, previously treated with cisplatin, developed an irreversible lethal renal failure with anuria, the day after 5 g/m2 bolus ifosfamide. Postrenal failure was excluded by echography. A prerenal component could have contributed to renal failure because of a transient hypotension, due to an increasing ascitis, occurring just before anuria. However, correction of the hemodynamic parameters did not improve renal function. Ifosfamide is a known nephrotoxic drug with demonstrated tubulopathies. We strongly suspect that this lethal anuria was mainly due to ifosfamide, occurring in a patient having received previous cisplatin chemotherapy and with poor kidney perfusion due to transient hypotension. We recommend careful use of ifosfamide in patients pretreated with nephrotoxic chemotherapy and inadequate renal perfusion. PMID- 2320801 TI - [Physiopathology, manometry and differential diagnosis of achalasia]. PMID- 2320802 TI - [Controlled frequency pacers]. PMID- 2320803 TI - [Primary cardiac tumors: myxoma of the left auricle]. PMID- 2320805 TI - [Lung and thorax surgery today]. PMID- 2320804 TI - [What is your diagnosis? Becker nevus (Synonyms: neviform melanosis, Becker melanosis]. PMID- 2320806 TI - [Decortication: indication and morbidity--a retrospective analysis]. AB - Decortication, that is excision of both the visceral and parietal pleura, has become a rarely performed operation. It is used for control of empyema of the pleura or recurrent malignant pleural effusion. During the last ten years at the University Hospital in Zurich 50 decortications were performed upon 49 patients. Mortality was 4%, however, death was due to the primary disease and not related to the operation. 38 of 50 decortications were straight forwards. The main complication was bleeding, needing re-thoracotomy in three patients and leading in five patients to a pneumothorax due to occlusion of the suction drains. We conclude, that if conservative treatment fails to result in a rapid progress, decortication should be performed immediately. PMID- 2320807 TI - [Correction of funnel chest using the Senning-Johanson method]. AB - Between 1962 and 1987 52 patients underwent surgical reconstruction of pectus excavatum at the University Hospital of Zurich using the Senning-Johanson method, first published in 1974. The technique of Senning-Johanson consists of a Y-shaped sternotomy and a transsection of the involved ribs from inside of the thoracic cage, thereby avoiding a dissection of the anterior chest wall. The average age of the 36 men and 16 women was 20 years (range 12-33). The internal sterno vertebral distance, which we consider to be a good parameter for determining the anatomic dimension of a funnel-chest, was extended by the operation from an average of 5.8 cm (range 2.5 to 10) to 10.1 cm (range 6.1 to 14) or 74% of the original value. The physical working capacity in sitting position was improved by 10%. The vital capacity was preoperatively normal and was not changed by the operation. Thirty-seven patients considered the operative result to be good, in twelve it was satisfactory, and in three bad. The funnel-chest repair using the Senning-Johanson method can be recommended as a successful procedure with relatively few complications for the adult patient. PMID- 2320808 TI - [Fever, dyspnea]. AB - A 52-year-old female complained about non-distinct symptoms such as fatigue, night sweats and bone pain. Because of a febrile bronchitis, chest X-ray was performed, which disclosed enlarged hilar nodes and intestinal and acinar pulmonary infiltrates. Endobronchial biopsy and cultures from bronchial aspirate permitted to diagnose infection by legionella concomitant with sarcoidosis. After antibiotic treatment for legionellosis over four weeks, immunosuppressive therapy for sarcoidosis was initiated with glucocorticoids. PMID- 2320809 TI - [A case from practice (168). Lupus-like syndrome with partial C2 and C4 deficiency - positive anticardiolipin antibodies]. PMID- 2320810 TI - [A case from practice (169). Liquorice-induced pseudohyperaldosteronism in a previously alcoholic woman caused by the drinking of an alcohol-free Pastis substitute beverage]. PMID- 2320811 TI - [What is your diagnosis? PUPPP-dermatosis (Lawley, 1979) = pruritic urticarial papules and plaques of pregnancy (pregnancy dermatosis)]. PMID- 2320812 TI - [ERCP under ceftriaxone antibiotic cover in patients with obstructive jaundice]. AB - The risk of cholangitis after ERCP has been reported to occur in up to 50% of patients with obstructive jaundice. Prophylactic antibiotics have therefore been advocated to reduce the risk. Here we report on the results of 46 patients with obstructive jaundice who were given 1 g of Ceftriaxone i.v. 30 to 60 min. prior to the procedure. Only one patient developed cholangitis with septicemia, which was treated conservatively. No side effects were observed in this group of patients. It is suggested that Ceftriaxone is an adequate prophylactic method to prevent cholangitis and septicemia in patients with obstructive jaundice. PMID- 2320813 TI - [The urease rapid test (CLO test). Attempt at statistical analysis for the evaluation of Campylobacter colonization in the gastric antrum]. AB - CLO-tests: A statistical analysis for the evaluation of the presence of Campylobacter pylori in antral mucosal biopsies. Antral biopsies taken in a sample of 475 endoscopy patients were positive for CLO on 21% of 77 controls, compared with 39% of non-ulcer dyspepsia (NUD) patients without and 69% with a history of former peptic ulcer. Epigastric pain was associated with a positive CLO-test more frequently than belching or heart burn. Patients with NUD of Turkish or Yugoslavian nationality had a significantly higher rate of positive CLO-reactions compared with Germans or Italians with the same diagnosis. In 96 patients with peptic ulcer, the percentage of positive CLO-test decreased significantly in old persons. PMID- 2320814 TI - [Herpetic esophagitis following renal transplantation]. AB - We report the case of a patient who developed herpes simplex oesophagitis less than one month after renal transplantation. Graft rejection treatment may have induced this infection. Diagnosis was suspected at endoscopy and was confirmed by biopsy. The patient was cured by intravenous acyclovir and temporary discontinuation of immunosuppressive medication. PMID- 2320815 TI - [Ulcer symptoms without demonstration of ulcer: causative therapy with demonstration of Helicobacter pylori]. AB - Helicobacter pylori-associated gastritis was found by endoscopy in 15 (= 28%) out of 53 patients presenting gastric pain of ulcer type without macroscopically detectable lesion of the gastric mucosa. Following a treatment of four weeks with bismuth subcitrate tablets (2 x 2 tablets daily), in 73% improvement of histological findings and in 87% elimination of bacteria could be attained. Thus, this causal therapy had a favourable effect on patient complaints. PMID- 2320816 TI - [Gallstone treatment using extracorporeal shockwave lithotripsy and adjuvant oral lysis: status and perspective]. AB - Three years of clinical experience and the results of the "First International Symposium of Biliary Lithotripsy" showed that extracorporeal shock waves disintegrate cholesterol, pigment and calcified stones into fragments of 1 to 8 mm in diameter. Since spontaneous passage of fragments through the bile ducts is not possible, the therapeutic goal must be achieved with adjuvant oral lysis of the fragments. Therefore, only cholesterol stones are suitable, and a contractile gallbladder as well as a limited stone volume are prerequisites. After one year of treatment, in 45 to 80% of patients complete clearance of stone fragments from the gallbladder is observed. During this period one third of the patients experiences occasional colics. Further severe complications have not been reported. PMID- 2320817 TI - [Subcutaneous administration of apomorphine in motor fluctuations in Parkinson's disease]. AB - Apomorphine, a dopaminergic agonist was given over a period of 12 months to 14 parkinsonian patients suffering from severe L-dopa induced on-off effects. Nine patients (mean age: 52 years; mean age at onset of the disease: 37 years), were treated by continuous infusion with a portable minipump, and 5 others by multiple injections with a penject. The mean duration of daily off periods was reduced by two thirds in all patients. The motor fluctuation intensity was only diminished in the 9 patients treated by continuous infusion. These patients received a mean apomorphine daily dose of 93 mg and L-dopa dosage was reduced by 53 p. 100. Red fibrous subcutaneous nodules occurred at the injection sites in all patients treated by infusion. This study confirms the effectiveness of subcutaneous apomorphine administration in the treatment of severe motor fluctuations. PMID- 2320818 TI - [Gadolinium-DTPA in the study of intracranial tumors in the adult]. AB - Thirty intracranial tumours were explored by MRI, using T1- and T2-weighted sequences, before and after intravenous injection of Gd-DTPA. Two-thirds of the intra-axial tumours were accurately detected on one section plane by MRI without Gd-DTPA, but in one quarter of the cases Gd-DTPA only delineated precisely the tumour. On the other hand, Gd-DTPA failed to detect certain tumours (benign gliomas) or showed only a small part of them (mixed grade gliomas), while they were detected by MRI without contrast injection. However, in such cases Gd-DTPA was useful for the stereotaxic biopsy of the tumour. Gd-DTPA appears of lesser interest in extra-axial tumours. Gd-DTPA is thus valuable for the neuroradiological diagnosis of brain tumours, particularly to evaluate the grade of gliomas and to confirm the diagnosis of recurrent growths. PMID- 2320819 TI - [A case of hemiballismus during cryptococcal meningitis]. AB - We present a case of hemiballismus related to cryptococcal meningitis. A 23 year old man was hospitalized because of involuntary movements of his left side, confusion, hyperpyrexia, neck stiffness, bilateral papilledema, right hemiparesis and bilateral pyramidal signs. Diagnosis was made by CSF examination demonstrating cryptococci by india ink. CT with contrast showed hyperdense lesions in the head of the right caudate nucleus, in the left internal capsule and in the frontal and occipital lobes. After treatment with amphotericin B, 5 fluorocytosine and haloperidol, he experienced rapid recovery with disappearance of hemiballismus. To our knowledge, this is the first report of hemiballismus caused by cryptococcal meningitis. PMID- 2320820 TI - [Frequency and indications of cesarean section]. PMID- 2320821 TI - [Infectious and hemorrhagic complications of cesarean section. Apropos of 2,220 procedures]. PMID- 2320822 TI - [The role of cesarean section after 32 weeks. Pediatric point of view]. PMID- 2320823 TI - [Delivery in cases of twin pregnancy]. AB - A retrospective analysis of 233 cases of twin pregnancies has demonstrated an increased frequency of prophylactic caesarean sections (27%) due to an increased performance of caesarean sections when the first twin is a breech and when premature babies are delivered before the 34th week of amenorrhea. When the first twin is a head, a natural delivery is possible with the same criteria as a single pregnancy. The vaginal delivery is also possible if the 2nd twin is a head. In deliveries where the 2nd twin is a breech, there is an increased frequency of early neonatal mortality and Apgar tests under 7 at 5 min, in comparison with the 2nd twin when it is a head. The type of delivery does not seem affected for babies over 1,500 grams. If the 2nd twin is a breech and under 1,500 g, a review of the literature and our results prompt us to broaden the indications of caesarean section. A delay before the birth of the 2nd twin, of under 10 min is usually associated with a better Apgar score at 1 min. without any significant differences at 5 min. It is advisable, at 38 weeks, to induce labor by rupturing the membranes and starting a perfusion of Syntocinon. If the conditions are unfavorable, pursuing the pregnancy requires a close supervision until term. PMID- 2320824 TI - Predicting bleeding in common ear, nose, and throat procedures: a prospective study. PMID- 2320826 TI - Solitary cervical node metastasis in renal cell carcinoma. PMID- 2320825 TI - Superior vena cava syndrome. PMID- 2320827 TI - Mortality from firearms in Rhode Island, 1980-1987. PMID- 2320828 TI - The durable power of attorney for health care: an important ingredient of sound health care. PMID- 2320829 TI - Detoxification of the chemically dependent patient. PMID- 2320831 TI - [Information in primary nursing care. How it is obtained and utilized?]. PMID- 2320830 TI - Resident report: a conference with many uses. PMID- 2320832 TI - [Blood samples in low-weight infants]. PMID- 2320833 TI - [Oxygen administration. A comparative study]. PMID- 2320834 TI - [Home care. Its strategic utility and objectives]. PMID- 2320835 TI - [Autotransfusions in scheduled surgery]. PMID- 2320836 TI - [Personal feminine hygiene and urinary infection]. PMID- 2320837 TI - [The nursing history. A practical guide]. PMID- 2320838 TI - [The anesthesia cart]. PMID- 2320839 TI - [Nursing before the challenge of the 90s]. PMID- 2320840 TI - [The reform of primary care]. PMID- 2320841 TI - [Sterilization with ethylene oxide. Its repercussions on the hospital environment]. PMID- 2320842 TI - [Postcholecystectomy nutrition]. PMID- 2320843 TI - [Nursing students learn in a primary care service]. PMID- 2320844 TI - [7 years of projecting the new concept of nursing to society]. PMID- 2320845 TI - [Quality control]. PMID- 2320846 TI - [Psychosexuality in the elderly. An education proposal]. PMID- 2320847 TI - [The tracking of obese patients in a nursing consultation. A protocol for action]. PMID- 2320848 TI - [Catheters for a hemodynamic study (II). Percutaneous transluminal coronary angioplasty]. PMID- 2320849 TI - [Emergency services overwhelmed]. PMID- 2320850 TI - We got ourselves (re)organized. PMID- 2320851 TI - What those "difficult" renal patients need from you. PMID- 2320852 TI - The power of non-narcotic pain relievers. PMID- 2320853 TI - Our nurses never left us. PMID- 2320854 TI - What's wrong with this patient? PMID- 2320856 TI - Patient teaching for x-ray and other diagnostics. PMID- 2320855 TI - Gallstones. Alternatives to surgery. PMID- 2320857 TI - Nursing homes can't afford cheap nursing care. PMID- 2320858 TI - When babies are born with orthopedic problems. PMID- 2320859 TI - The abnormal infant: protecting yourself against blame. PMID- 2320860 TI - Piecing together the osteoporosis puzzle. PMID- 2320862 TI - Nursing and Ontario's new pay equity. PMID- 2320861 TI - Patient teaching for home i.v. therapy. PMID- 2320863 TI - RNAO strengthens political role in 1990. PMID- 2320864 TI - Proposed legislation should protect individual rights. PMID- 2320865 TI - Bomb scare spurs innovative patient evacuation plan. PMID- 2320866 TI - [Angiography findings before and following transplantation of free myocutaneous flaps]. AB - Prerequisite for successful split-skin flap transplants of myocutaneous flaps is the presence of adequate adjacent afferent and efferent vessels, thus making an arteriography of the receiving region mandatory during surgery preparation. In 20 or 29 patients in whom a split myocutaneous flap was transplanted to the lower leg, angiography revealed 22 pathological or other therapyrelevant findings. Besides the afferent vessels it is basically necessary to visualise the peripheral efferent pathways in order to prevent that vascular anastomosis to the split-skin flap obstructs the blood supply of the leg. PMID- 2320867 TI - [Large epidermoid cyst of the posterior cranial fossa]. AB - An extensive epidermoid cyst in the posterior fossa was diagnosed in a 59 year old male patient. The most valuable indicator for differential diagnosis was given by plain skull x-ray showing a peripheral zone of sclerosis as the leading x-ray sign of epidermoids. CT and MRI complemented the preoperative diagnostic measurements. PMID- 2320868 TI - [Osteomyelitis (spinal infection, spondylitis, spondylodiscitis) of the dens axis]. AB - The authors present a rare case of osteomyelitis of the dens axis. The diagnostic procedure concerning vertebral infection is discussed. In this connection, particularly MRI is of great importance in early diagnosis. PMID- 2320869 TI - [Computerized tomography findings in rare malignant processes of the thorax]. AB - The CT findings in 21 patients with rare malignant space-occupying growths in the thorax were evaluated retrospectively under morphological aspects. The possibility of rare malignant thoracic space-occupying growths should be considered mainly 1) in patients who are either very young or of very old age, 2) if risk factors are absent, especially abuse of nicotine, 3) if there are large inhomogeneous growths, possibly with calcareous areas or necrotic zones and sharp marginal delineation in the node status, 4) if the tumour localisation is atypical of bronchial carcinoma. PMID- 2320870 TI - [Isolated pleural recurrence of Hodgkin's disease]. AB - Relapses of Hodgkin's disease are predominantly nodal or systemic. An extranodal manifestation is a rare exception. We report on a patient who developed an isolated pleural relapse at the margin of the irradiation field after successful radiotherapy of a Hodgkin's disease stage I. PMID- 2320871 TI - [Value and reliability of hypotonic duodenography in chronic pancreatitis]. AB - The incidence of pathologic duodenal abnormalities in patients suffering from chronic recurrent pancreatitis is derived from a retrospective analysis of 128 hypotonic duodenographies. The value of established diagnostic criteria and the present indication for a hypotonic duodenography in chronic pancreatitis are determined. PMID- 2320872 TI - [Colorectal invagination in adults following removal of a sigmoid polyp]. AB - A unusual case of colorectal intussusception after transanal surgery of a polyp of the sigmoid colon is presented. Clinical Signs consisted of transanal bleeding and mucous diarrhoe. The diagnosis was established after an enema with water soluble contrast media and computed tomography of the pelvis. The radiological appearance was similar to that of intussusception at other sites of the large bowel: The enema showed a sharply outlined filling defect whereas CT demonstrated a target-like intraluminal mass. PMID- 2320873 TI - [Methodologic optimization of computerized tomography diagnosis of the large intestine]. AB - Examination of the intestine by computed tomography can supply additional information on diseases of the intestinal wall. However, the successful interpretation of the bowel wall by CT requires a special technique by which normal structures are opacified, identified and not mistaken for abnormal masses. The rectal administration of water improves the visualisation of the bowel wall and the diagnostic accuracy. This safe, reliable and acceptable method for opacifying the colon and rectum is described. Its value is demonstrated by means of normal and pathological examples. PMID- 2320874 TI - [Double kidney with ectopic ureteral orifice: a case report]. AB - An ectopic ureteric opening is a relatively rare malformation, diagnosed mostly in young age because of typical signs and symptoms and more often found in female patients. The diagnosis of this malformation in adults is unusual and can be difficult because of untypical signs and symptoms, as represented in the following case report. PMID- 2320875 TI - [Glucocorticoids: mode of action and pharmacokinetics]. AB - Glucocorticoids are used in therapeutics for their anti-inflammatory, anti allergic and immunosuppressant activities. These effects are partly due to the ability of glucocorticoids to inhibit cell activation, since they block the transmission of cell stimulation signals through the cell membrane. They also inhibit the release of numerous cellular mediators, such as interleukins, prostaglandins, leukotrienes, etc. which intervene in immunological reactions. Finally, their cytostatic effect justifies their inclusion in many chemotherapeutic regimens. Although glucocorticoids have been widely used for several decades, many questions concerning their pharmacokinetics and mechanism of action remain unanswered. PMID- 2320876 TI - [General corticotherapy and its complications]. AB - Prescribing a corticosteroid treatment requires a three-step strategy: a) to chose the appropriate drug, its dosage regimen, and its route of administration; b) to reduce the side effects by taking the status of the patient into account, and by adopting various preventive recommendations; c) to reduce the dosage before deciding to stop treatment according to specific rules. This "good practice" of corticosteroid therapy makes it a well tolerated and observed treatment, and alleviates the fears that is often created in the patient and his physician. PMID- 2320877 TI - [Practical application of local corticotherapy: topical corticosteroids]. AB - Topical corticosteroids are mainly used for their anti-inflammatory activity by a complex mechanism Which involves vasoconstriction, inhibition of leucocyte migration and stabilization of lysosomal membranes with inhibition of inflammation factors synthesis. In non-inflammatory skin diseases, they are used for their antimitotic effect or their ability to inhibit the synthesis of several macromolecules forming the connective tissue. So many topical corticosteroids are now available that they must be classified according to their level of activity, as measured by a vasoconstriction test. The European classification system has four levels numbered I to IV in descending order of potency. The choice of activity level depends on the patient's age and on the location, extent and acute or chronic character of the lesions. Creams are the most versatile preparations. Topical corticosteroids are contra-indicated in all infective skin diseases. Penetration through the skin varies according to the corticosteroid utilized, to the state of the skin on which it is applied and to the modalities of its applications. Irreversible skin atrophy is usually observed only after prolonged use of topical steroids levels I and II. PMID- 2320878 TI - [Intra-articular injection of corticosteroids]. AB - The corticosteroids administered by intra-articular injection are reviewed, together with their indications, contra-indications, precautions of use and side effects. Emphasis is laid on some points of detail which may help the users. PMID- 2320879 TI - [Corticosteroids and ophthalmology]. AB - Corticosteroids are widely used in the treatment of inflammatory and immunological diseases of the eye. They are given by three routes: topical application, periocular injection and systemic administration. Topical application, periocular injection and systemic administration. Topical application is used for anterior inflammatory diseases, such as conjunctivitis, keratitis or anterior uveitis. Posterior uveitis is treated with systemic and local injections. Herpetic keratitis is a contra-indications to the use of corticosteroids. Ocular side-effects are observed with systemic administration as well as with topical applications and local injections. They include posterior subcapsular cataract, rise of intraocular pressure and even glaucoma, failure in healing of corneal wounds and exacerbation of ocular infections. These side effects are not always reversible when treatment is stopped. Prevention consists of repeated eye examination. PMID- 2320880 TI - [Inhaled corticotherapy]. AB - Inhaled corticosteroids are active against bronchial inflammation, a major component of asthma in adults. They constitute a good alternative to systemic corticosteroid therapy in most cases, since their side-effects are infinitely less important. However, a strict inhalation technique is required for this treatment to be effective. PMID- 2320881 TI - [Endocrine consequences of corticotherapy. Weaning from long-term corticotherapy]. AB - Long term corticosteroid therapy has multiple effects on the endocrine system. These include adrenocortical suppression in high doses, alteration of gonadotropic and gonadal secretion, slowing down of long bone growth and bone maturation in children, osteoporosis in adults, alteration of the thyrotropic function and changes in thyroxine peripheral metabolism, diabetogenic effect. The list is not exhaustive, and there are more complex effects on the secretion of prolactin, pancreatic peptides, VIP, etc. Because of these various effects, the pros and cons of long term corticosteroid therapy must be carefully weighted, and if it is necessary steroids should be prescribed in such a way as to limit their side-effects: at best one dose taken in the morning every other day, together with the prescription of calcium, of a salt-free diet and, in some cases, of androgens or oestrogens. Weaning must be carried out with caution, to avoid rebound of the disease treated, and with substitution of hydrocortisone when the corticosteroid dosage reaches 5 mg per day of prednisone or equivalent and can be interrupted. The functional soundness or alteration of the corticotropic and adrenal functions must then be evaluated by testing corticotropic and adrenal functions must then be evaluated by testing the adrenocortical response to tetracosactrin, or even better by measuring early morning concentrations of blood cortisol. Depending on the results obtained, hydrocortisone can be withdrawn and limited to episodes of stress, or continued until ACTH and endogenous cortisol levels have returned to normal values. PMID- 2320882 TI - [Bone and osteo-articular complications of corticotherapy]. AB - Osteoporosis and epiphyseal aseptic bone necrosis are side-effects of corticosteroid therapy that must be detected and prevented. The incidence of osteoporosis depends on whether radiology or densitometry are used for its evaluation. Bone loss is accounted for by osteoblast depression and decreased intestinal absorption of calcium, responsible for secondary hyperparathyroidism. The clinical progress of steroid-induced osteoporosis is often impressive. Plasma osteocalcin levels are lowered. Nowadays, non-invasive methods of bone mass measurement are indispensable for detection and follow-up. Prevention rests on adjustment of corticosteroid therapy and, above all, on the prescription of calcium and vitamin D; fluoride constitutes the curative treatment. Corticosteroid dosage plays a role in the occurrence of aseptic bone necrosis at an early stage of treatment. The lesions, often multiple and progressive, mostly affect the femur. MRI is the most sensitive examination for early detection. When medical treatment has failed, total hip replacement may be considered. PMID- 2320883 TI - [Psychiatric complications of corticotherapy]. AB - Corticosteroid therapy may induce numerous psychiatric disorders. Minor changes of the euphoric mood type are observed in 75% of the patients under treatment. Major adverse effects are encountered in not more than about 5% of the cases. They consist of acute polymorphous psychotic manifestations which may be manic or depressive or, when high doses of corticosteroids are taken, of the organic confusion type. Such manifestations are particularly frequent in women and in some diseases such as lupus erythematosus or pemphigus. In the vast majority of cases they follow a favourable course when corticosteroids are reduced or discontinued and a symptomatic treatment with neuroleptic drugs is prescribed. Psychic dependence on corticosteroids and withdrawal syndromes have also been reported. PMID- 2320884 TI - [Monitoring of treatment with vitamin K antagonists: a plea for "INR" (International Normalized Ratio)]. PMID- 2320885 TI - [Tobacco and ulcer disease]. PMID- 2320886 TI - [Increased erythrocyte sedimentation. Diagnostic orientation and management]. PMID- 2320887 TI - [Heart failure in children. Etiology, diagnosis, treatment]. PMID- 2320888 TI - [Gilbert's disease. Physiopathology, diagnosis]. PMID- 2320889 TI - [Enuresis. Diagnosis, principles of treatment]. PMID- 2320890 TI - [Chronic restrictive respiratory failure. Etiology, physiopathology, diagnosis, development and prognosis, treatment]. PMID- 2320891 TI - [Foreign bodies in the eyeball. Diagnosis, principles of treatment]. PMID- 2320892 TI - [Results of cerebrospinal fluid examination. Significance of results (normal, hemorrhagic, purulent, lymphocytic, inflammatory, albumin-cytologic dissociation]. PMID- 2320893 TI - [Epidemiology of tuberculosis]. AB - In 1990, tuberculosis remains a major, world-wide problem, with 50 p. cent of the world's population being infected by Mycobacterium tuberculosis. In France, the latest known figures show a continuous decrease in the incidence of tuberculosis, despite the risk due to the development of AIDS, but the situation is totally different in developing countries where tuberculosis ranks first among the infections associated with AIDS. This TB-AIDS association makes it necessary to maintain in epidemiological tuberculosis watching system. PMID- 2320894 TI - [Tuberculosis and mycobacterioses in the AIDS era]. AB - The emergence of the HIV infection has been concomitant with a halt, noticed as early as 1986, in the regression of tuberculosis. The resurgence of tuberculosis, and indeed of all mycobacterioses, is determined by the HIV-induced alteration of cell-mediated immunity, which encourages the development of tuberculous and non tuberculous bacteria. These bacteria themselves have an immunosuppressant effect on CD4 lymphocytes and macrophages, thus contributing to the progress of the HIV infection. The HIV and tuberculous infections therefore constitute a kind of "diabolical duo", the degree of endemia of one of these two diseases being influenced by the other and reciprocally. The final result is a menace to all countries where tuberculosis is strongly endemic and where the HIV infection is spreading. Only one of these infections, tuberculosis, is within the reach of our therapeutic armentarium. Patients must be investigated for tuberculosis systematically and actively--even though this disease may be hidden by misleading clinical signs and symptoms of AIDS--in order to treat it and separate, at least partially, the diabolical duettists. PMID- 2320895 TI - [Bacteriologic basis for the treatment of tuberculosis]. AB - To be fully effective, short-course chemotherapy for tuberculosis should take into account the slow growth rate, high oxygen requirement and high drug resistant mutant emergence rate of Mycobacterium tuberculosis, as well as the type of the lesions observed and the specific activity of each antituberculous drug. Due to their unique sterilizing activities against bacilli that are not actively metabolizing, rifampicin and pyrazinamide are the key drugs for short course chemotherapy. To prevent the selection of drug-resistant mutants and the occurrence of therapeutic failures, a combination of isoniazid, rifampicin, pyrazinamide and ethambutol should be given during the first two months of treatment. To kill persisting M. tuberculosis, and thus avoid posttreatment relapses, the isoniazid-rifampicin combination should be prescribed for a further four months. PMID- 2320896 TI - [Therapeutic modalities in pulmonary tuberculosis]. AB - In 1990, specific antituberculous chemotherapy can cure almost 100 p. cent of patients with pulmonary tuberculosis in France, provided practitioners follow strict therapeutic rules and patients' compliance with treatment is perfect. A single standard treatment is proposed for those patients whose tuberculosis has never previously been treated; it consists of a six months' course of isoniazid (5 mg/kg/day) and rifampicin (10 mg/kg/day); combined with ethambutol (20 mg/kg/day) and pyrazinamide (30 mg/kg/day) during the first two months. This treatment must be administered under regular medical supervision, and it must be prolonged for some time after cure has been obtained. In case of relapse or in some special situations (e.g. pregnant women, HIV positive patients, serofibrinous pleurisy, complex anatomico-clinical forms of the disease) treatment is more difficult, but it should always give favourable results. PMID- 2320897 TI - [Cutaneous reactions to tuberculin and BCG vaccine]. AB - The only available method for quantitative exploration of skin allergy to tuberculin is intradermal injection, since there is no other satisfactory method to evaluate the induration observed. Below 5 mm the induration has no significance. Between 5 and 10 mm it corresponds to an allergic reaction induced by BCG vaccine or by usually inapparent infections due to atypical mycobacteria. A diameter of 10 mm or more suggests either M. tuberculosis infection or allergy to BCG. The intensity of allergic reaction varies under the influence of numerous factors which may be genetic or nutritional, or associated with viral infections, antiviral vaccines and medicinal treatments. Exploring this allergy is of interest on the scores: (1) for epidemiological purposes, to obtain information on the annual risk tuberculosis infection or on the quality of the protection conferred by the vaccine in a given population; (2) for diagnostic purposes, to detect tuberculosis, and especially primary tuberculosis in children; (3) for vaccinal purposes, to determine the limitation of BCG. In subjects who have been vaccinated tuberculosis is rare but remains possible, and in such cases reactions to tuberculin may be difficult or even impossible to interpret. PMID- 2320898 TI - [Chemoprophylaxis of tuberculosis]. AB - Chemoprophylaxis of tuberculosis may be primary or secondary. Primary chemoprophylaxis is intended for infants and children with negative tuberculin tests and exposed to contagion, in order to avoid primary tuberculosis. It lasts for three months and consists of oral isoniazide in one single daily dose of 5 to 10 mg/kg. Secondary chemoprophylaxis applies to all subjects, but principally to children, with a tuberculin test that has recently become positive in the absence of BCG vaccination. Its purpose is to protect against clinical tuberculosis. It lasts for six months and consists of isoniazid combined with rifampicin. PMID- 2320899 TI - [Value of multiple daily doses in radiotherapy: hyperfractionation]. PMID- 2320900 TI - [Genetic predisposition to alcoholism]. PMID- 2320901 TI - [Bacterial virulence]. PMID- 2320902 TI - [Non-traumatic coma. Diagnostic orientation and management]. PMID- 2320903 TI - [Laryngitis in children. Diagnosis, treatment principles, (recommendations for hospitalization)]. PMID- 2320904 TI - [Fracture of the upper end of the femur. Etiology, physiopathology, diagnosis, treatment principles]. PMID- 2320905 TI - [Foreign bodies of the upper airway in children. Diagnosis, treatment principles]. PMID- 2320906 TI - [Pathologic thoracic radiography: an intraparenchymatous round opacity]. PMID- 2320907 TI - [Reye's syndrome]. AB - Reye's syndrome is an acute disease of childhood characterized by non inflammatory cerebral pathology associated with hepatic pathology (steatosis). When untreated, its course is very severe, with a 30 p. 100 mortality rate. The diagnosis rests on the occurrence of a suggestive clinical sequence (influenza like syndrome followed by a latent period, then vomiting and disturbances of consciousness) and on particular laboratory findings: high serum ammonia and transaminase levels, hypoprothrombinaemia and frequent hypoglycaemia in neonates. As soon as the condition is diagnosed, massive intravenous carbohydrate therapy must be initiated. Several factors intervene in the pathogenesis of Reye's syndrome; the responsibility of treatment with salicylates and of hereditary enzymopathies is discussed. PMID- 2320908 TI - [Drowning in children]. AB - Drowning is one of the most common causes of death in children. Near-drowning is even more frequent: near-drowning/drowning ratio is approximately 9-10/1. The age groups between 1 and 3 years and 15 and 25 years are most likely to be at risk for submersion accidents. The majority of drowning accidents in children occur in swimming pools and bathtubs. The awake or stuporous victim has an excellent prognosis. In comatose patients, the prognosis is directly proportional to the severity of coma. Treatment is mostly supportive. Despite optimal care, it is not infrequent for a near-drowning accident to end in death or severe neurological handicap. Prevention must be a priority for the medical profession. PMID- 2320909 TI - [Antibiotic therapy of nosocomial infections in children]. AB - The choice of antibiotics for the treatment of hospital-acquired infections in children is a rational choice based on the child's general condition, on the site of infection, on the most probable pathogens and on their current sensitivity to antibiotics. The antibiotic chosen must reach bactericidal concentrations at the site of infection for rapid reduction or the inoculum and to limit the systemic spread of infection, thereby decreasing the risk of a rapidly expanding infectious process in the younger children. The optimal antibiotic is selected on the basis of what is known about bacterial resistance. General therapeutic rules must be adjusted to the epidemiological situation prevailing in each hospital department. PMID- 2320910 TI - [Analgesia-sedation in pediatric resuscitation: indications, modalities]. AB - Recently in pediatric intensive care, sedative and analgesic drugs are being used more frequently, not only for painful and stressful procedures, but also to improve the techniques of intensive care and the patient's comfort. Benzodiazepines are the most common drugs used for sedation, and narcotics for pain. PMID- 2320911 TI - [Transplantation in children: selection of donors and organization of organ procurement]. AB - The rise of organ transplantation in children has resulted in an acute donor shortage. In 1987, a study was undertaken by the French-speaking Group of Paediatric Intensive Care with a triple goal: to evaluate the number of potential organ donors, to list and count the organs that have effectively been removed and to sensitize the teams of intensive care units (ICU) to the transplantation problem. This study showed that brain death occurs in one-third of the infants and children who die (i.e. about 200 each year). As a result of this study, over a two-years period the number of children whose organs had been removed (42 in 1988) as well as the number of organ procurement centres and multiple organ procurements have increased. One-half of the non-procurements are due to the parents' refusal, so that further advances are possible by sensitizing not only ICU teams but also the general public. It seems that the best solution would be to set up local organizations that would enable procurements to be performed within Paediatric ICU's. France-Transplant is of invaluable help to identify organ receivers and co-ordinate the activities of procurement teams. PMID- 2320912 TI - [Resuscitation of children with brain death in view of organ procurement for therapeutic use]. AB - Among the different stages from donor to recipient, the intensive care of children in a state of brain death (BD) is of paramount importance, the first step being having this goal in mind. As soon as procurement is contemplated and medico-legal formalities have been completed, all potentially involved persons and institutions (France-transplant, procurement and transplantation teams, immunology laboratory, recipients) must be contacted. Intensive care, started at the stage of irreversible coma, will be pursued near the place where procurement will be performed, geared to the obtention of multiple organs. Transportation is often required (for arteriography or procurement), but is carries a risk since BD creates an unstable situation which at any moment may turn into cardiac arrest. Under such conditions, intensive care has two main objectives: 1) to ensure adequate haemodynamics and tissue oxygen supplies, and 2) to avoid infection. After a 10 to 20 hours period of intensive care and after procurement a detailed report on both surgery and intensive care must be laid down. PMID- 2320913 TI - [Significance of cathepsin D in breast cancer]. PMID- 2320914 TI - [Nutrition and microbes]. PMID- 2320915 TI - [Chronic diarrhea without small intestine malabsorption. Etiology, diagnosis, course and prognosis, principles of treatment]. PMID- 2320916 TI - [External hemorrhoidal thromboses. Diagnosis, course and prognosis]. PMID- 2320917 TI - [Anal fissure. Diagnosis, principles of treatment]. PMID- 2320918 TI - [Transmissible diseases: prevention (school eviction, vaccination, seroprevention, chemoprevention)]. PMID- 2320919 TI - [Bacterial and viral pneumopathies. Epidemiology, etiology, physiopathology, diagnosis, course and prognosis, treatment]. PMID- 2320921 TI - [Otalgia. Diagnostic orientation and management]. PMID- 2320920 TI - [Conductive deafness. Diagnosis, treatment]. PMID- 2320922 TI - [Hypercalcemia and vital prognosis of cancers with bone metastases]. PMID- 2320923 TI - [Scapular function index. Proposal of a numbered code. Critical study and results]. PMID- 2320924 TI - [Large granular lymphocytes and neutropenia in ankylosing spondylarthritis]. PMID- 2320925 TI - [Osteoporosis with androgenic deficiency in a jogger]. PMID- 2320926 TI - [Behcet's disease and class II and III antigens of the major histocompatibility complex]. PMID- 2320927 TI - [Prognostic value of soluble interleukin 2 receptors in the synovial fluid in rheumatoid arthritis]. PMID- 2320928 TI - [Subchondral bone wear of the tibial plateau in femorotibial knee osteoarthritis. Radiologic aspects in the profile incidence. Clinical, anatomical correlations and consequences]. PMID- 2320929 TI - [Epiphyseal bone pain caused by cyclosporin A in 28 patients with renal transplantation]. PMID- 2320930 TI - [Osteomalacia caused by deficiency. Correlations of radioclinical and histomorphometric data]. PMID- 2320931 TI - [The inching test in the diagnosis of carpal tunnel syndrome. Apropos of 20 cases]. PMID- 2320932 TI - [Bone rarefaction in weightlessness. Osteoporosis-disease or osteopenia caused by rapid aging?]. PMID- 2320933 TI - [MRI and intraspinal neurinoma. Apropos of 2 cases]. PMID- 2320934 TI - [Lupus caused by atenolol and narrow lumbar tunnel syndrome]. PMID- 2320935 TI - [Candida albicans cubital tenosynovitis. Apropos of a case with lymphocytic synovial fluid and outpatient treatment using a new antifungal agent, fluconazole]. PMID- 2320936 TI - [Ankylosing spondylitis and Darier's disease. A new spondyloarthropathy?]. PMID- 2320937 TI - [The filum terminale. An uncommon site of spinal meningioma]. PMID- 2320938 TI - [Postmenopausal osteoporosis: early detection of subjects at risk using spinal dual photon absorptiometry]. AB - With quantification techniques of the spinal bone condition, especially with spinal biphotonic absorptiometry, early screening of patients risking subsequent development of osteoporosis complicated with vertebral compression is possible. An investigation was conducted in Lower Normandy, in 386 women who had undergone menopause or an ovariectomy, with ages ranging between 40 and 56 years; 274 were in a peri-menopausal state. We had previously established a curve of the bone mineral content according to age. From this curve, in semilogarhythmic representation, we assessed each patient's risk. This risk is considered as high in 30 p. cent of the patients, non existent in 52 p. cent and 18 p. cent are borderline. The percentage of high risk patients increases with the number of years since menopause. It is hoped that the incidence of osteoporosis will decrease with early screening and preventive therapeutic measures. PMID- 2320939 TI - Non-steroidal anti-inflammatory drugs and gastric DNA synthesis. AB - In vitro incubation of endoscopic gastric antral biopsy specimens with tritiated thymidine, with confirmatory autoradiography, was used to assess gastric epithelial cell turnover in man and to investigate the effects of chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs). In the absence of NSAID administration, macroscopic erosions and ulceration in the antrum were associated with enhanced gastric epithelial cell proliferation. In patients taking NSAIDs erosions occurred without a compensatory increase in epithelial cell DNA synthesis. The failure to respond to injury by enhancing epithelial cell proliferation is likely to be an important factor in NSAID-induced gastric damage and supports a role for prostaglandins in enhancing mucosal repair by increasing epithelial cell generation. PMID- 2320940 TI - Phosphate transport adaptation in rat jejunum and plasma level of 1,25 dihydroxyvitamin D3. AB - Intestinal absorption of inorganic phosphate (Pi) increases in response to a reduction in the dietary supply of Pi. In this work this adaptive response has been characterized in jejunal brush border membrane vesicles and studied in temporal relationship with the change in the plasma level of 1,25(OH)2D3. The results indicate that in rat jejunal brush border membrane vesicles the activity of the sodium-dependent Pi transport system is stimulated by a low Pi diet. This adaptive response was the result of an increase in the Vmax and a reduction in the Km of the cotransport system. This change in Pi transport was correlated with an increase in the circulating level of 1,25(OH)2D3 in a time-related fashion. In conclusion, these results are consistent with the notion that Pi restriction leads to an increase in Pi transport activity in the luminal membrane of the intestine. A time course study suggests that the elevation in plasma 1,25(OH)2D3 might be involved in the adaptation of the intestinal Pi transport system to Pi restriction. PMID- 2320941 TI - Digital ambulatory monitoring of small-bowel motility. AB - This paper describes a new technique for ambulatory long-term monitoring of small bowel motility. Intraluminal pressure was measured with a silicon catheter with two strain-gauge transducers spaced 15 cm apart. Pressure data were stored in a portable memory unit. Initial studies showed that a recording frequency of 2 Hz was sufficient for obtaining reliable motility measurements. Twelve-hour recordings of motility in the upper jejunum were done in 12 healthy volunteers. After a 1964-kJ meal the median duration of fed-state motility was 4.6 h (3.4-5.3 h, interquartile range). The activity front of the migrating motor complex propagated with a velocity of 2.7-5.3 cm/min, and the median cycle length was 77 (40-103) min. The frequency of contractions in the activity front was 11.4 (10.9 11.6)/min at the proximal transducer. This new technique enables small-bowel motility to be monitored over longer periods of time and with much less inconvenience to the patient than previously used methods. PMID- 2320942 TI - Atypical coeliac disease found with serologic screening. AB - Eighteen patients with coeliac disease were found by screening for reticulin antibodies of unselected sera at the time when determination of various tissue antibodies was requested. Joint disease, allergic and pulmonary disorders, and diabetes were particularly observed. IgA class reticulin antibody, in particular, proved to be specific for coeliac disease. Most patients with coeliac disease also had positive serum gliadin antibodies. Abdominal symptoms and signs of malabsorption were slight and infrequent. In most patients a gluten-free diet resulted in the improvement of jejunal mucosal histology, and serum reticulum and gliadin antibody titres decreased simultaneously, reflecting the appropriateness of the diet. Coeliac disease often has mild and atypical symptoms, and, particularly in certain disease groups, screening with reticulin antibody test seems to be appropriate. PMID- 2320943 TI - Trends in and value and consequences of radiologic imaging of perforated gastroduodenal ulcer. A 50-year experience. AB - The trends in and value and consequences of radiologic imaging in 1128 patients with perforated gastroduodenal ulcer have been studied over the 50-year period 1935-1985. The proportion of patients undergoing plain X-ray studies increased from 4% in the first 5-year period (1935-1939) to 94% in the last (1980-1985). Pneumoperitoneum was found in 77% of those undergoing X-ray studies. Water soluble contrast studies were introduced in 1960, and in the three 5-year periods 1970-1985 from 8% to 13% underwent such imaging. Leakage was demonstrated in 60% of those undergoing contrast studies. Contrast studies have had a limited role in the pretreatment evaluation of these patients. The frequency of pneumoperitoneum was fairly constant over the 50-year period, and the only patient characteristic that influenced the occurrence of free gas in the abdominal cavity was age, with a higher proportion of patients with pneumoperitoneum in old patients. Any radiologic study increased treatment delay by at least 2 h. PMID- 2320944 TI - Alterations in body composition after gastroplasty for morbid obesity. AB - Body compositional changes during rapid weight loss and after weight stabilization were prospectively studied in morbidly obese patients undergoing gastroplasty operations. Body composition was studied preoperatively and 6 and 24 months postoperatively in 23 patients by use of a total body counter (40K) and an isotope dilution technique. The mean fat mass, cell mass, and intracellular water (ICW) decreased during the first 6 months (p less than 0.001) and remained unchanged at the 24-month test. However, the mean liters of extracellular water (ECW) did not change. Consequently, the ECW/ICW ratio, high in states of malnutrition, rose above postoperative levels. A strong correlation was found between decreases in cell mass and increases in the ECW/ICW ratio. PMID- 2320945 TI - Influence of jejunal hypertonic glucose infusion on sham-feeding-stimulated gastric acid secretion: evidence of a defective mechanism in duodenal ulcer patients. AB - The aims of the present study were to determine in 14 healthy subjects and 14 duodenal ulcer patients the reproducibility of the acid secretory response to a modified sham-feeding test and the effect on this response of intrajejunal hypertonic glucose instillation, in order to evaluate the possibility of the existence of a defective inhibition of the cephalic phase of gastric acid secretion in duodenal ulcer disease. The reproducibility of the acid secretory response to a modified sham-feeding test was demonstrated in both groups in two consecutive tests. The hypertonic glucose instillation produced a significant inhibition of the acid secretory response to modified sham feeding only in the healthy subjects, suggesting that duodenal ulcer patients may have a defective mechanism of acid inhibition during vagal stimulation by modified sham feeding. Non-significant changes were observed in plasma gastrin and pancreatic glucagon levels. PMID- 2320946 TI - Effect of calcium deficiency on vitamin B12 absorption in rats. AB - The influence of calcium on vitamin B12 absorption was investigated in two experiments. In the first we investigated whether B12 malabsorption in rats with biliary diversion through choledochocolic fistula is caused by deficiency of calcium in the small intestine. Calcium concentrations were measured in 10 fistula- and 10 sham-operated rats. Fistula rats had steatorrhea, but the concentration of calcium in the intestinal lumen was increased. In the second experiment we studied the effect of calcium deficiency on B12 absorption. Ten young rats were fed a low-calcium diet and 10 rats a control diet for 4 weeks. Rats on the low-calcium diet had moderately reduced calcium concentration in the blood and in the intestinal juice but unaltered calcium concentration in the cytosol fraction of intestinal mucosal scrapings. The absorption of 57CoB12 was unimpaired. This suggests that moderate calcium deficiency does not influence the intestinal absorption of vitamin B12 in the rat. PMID- 2320947 TI - Polyps in the gallbladder. A prevalence study. AB - The prevalence of gallbladder polyps as assessed by ultrasonography in a random population was 4.6% among men and 4.3% among women. The size of most polyps was 3 mm or more but never exceeded 10 mm. The prevalence of polyps was not significantly associated with age, sex, social factors, weight factors, physical activity, diabetes mellitus, pregnancies, use of exogenous female hormones, intake of alcohol, or plasma lipids. Polyps among men were significantly associated with a history of no smoking. This lack of risk factor profile resembled that of cholesterolosis, as seen in the literature, whereas it was quite different from that of gallstones. It is concluded that polyps in the gallbladder are common in a random population, and, although it is known from the literature that some cases may represent gallstones, the vast majority most probably represent the polypoid variation of cholesterolosis. PMID- 2320948 TI - Measurements of serum IgA and IgG activities to dietary antigens. A prospective study of the diagnostic usefulness in adult coeliac disease. AB - Serum samples from 458 consecutive adult patients with intestinal symptoms and/or suspected food intolerance were examined for IgG and IgA antibody activities to gluten, egg, and cow's milk antigens by an enzyme-linked immunosorbent assay (ELISA). Increased IgA and/or IgG activities to gluten were seen in 61 patients: 35 had coeliac disease (CD) as suggested by jejunal villous atrophy and subsequent histologic and/or clinical improvement on a gluten-free diet; 4 were previously diagnosed CD patients with clinically suspected dietary failure; 2 had dermatitis herpetiformis with a CD-like intestinal morphology; and 3 had possible gluten intolerance without villous atrophy. The rest had other disorders that might have affected the permeability of the gastrointestinal mucosa or the hepatic IgA catabolism. When the IgA activity to gluten was increased, neither the IgA/IgG activities to nongluten antigens nor the ratio of nongluten to gluten antibodies could discriminate between CD patients and those without CD. However, the median IgA activity to gluten was significantly higher in the CD group. The probability for CD thus increased from 33% in patients with IgA activity to gluten between 0.4 and 0.8 OD units to 90% in those with such activity above 2.4 OD units. Nevertheless, seven untreated CD patients had IgG and IgA activities to gluten within the normal range. ELISA determinations of serum antibodies to gluten antigens are a valuable adjunct in the diagnosis of adult CD, but a negative test does not exclude this disorder. PMID- 2320949 TI - Telenzepine, a new M1-receptor antagonist, is a more potent inhibitor of pentagastrin-stimulated gastric acid output than pirenzepine in dogs. AB - In conscious dogs with a gastric fistula we compared the action of different doses of telenzepine (ranging from 1 to 243 nmol/kg/h) and pirenzepine (ranging from 4.7 to 1170 nmol/kg/h) on gastric acid output in response to pentagastrin (1 to 8 micrograms/kg/h). Pentagastrin caused a dose-dependent increase in gastric acid output. A dose of 27 nmol/kg/h and all subsequent doses of telenzepine and a dose of 130 nmol/kg/h and all higher doses of pirenzepine significantly inhibited (up to 74% of control values) the gastric acid response to pentagastrin. Doses above 27 nmol/kg/h of telenzepine and doses above 130 nmol/kg/h of pirenzepine did not further inhibit the gastric acid output. Only the highest doses of telenzepine (243 nmol/kg/h) and pirenzepine (1170 nmol/kg/h) significantly increased heart rate from 66 +/- 3.1 to 77.1 +/- 3.9 and 72.5 +/- 3.2, respectively (beats/min, chi +/- SEM, n = 6). Differences between both drugs were not found with regard to cardiovascular responses of equipotent doses. We conclude that in conscious dogs with an intact stomach, the new M1-receptor antagonist telenzepine is, on a molar basis, more than 4.7 times more potent than pirenzepine in inhibiting pentagastrin-stimulated gastric acid output. This inhibition occurs at doses that do not increase heart rate, and, therefore, probably cause few systemic effects. PMID- 2320950 TI - Effect of pancreatic enzymes in non-ulcer dyspepsia. A pilot study. AB - The symptomatic effect of pancreatic enzymes was examined in 37 patients with non ulcer dyspepsia (NUD) recruited from general practice by means of a 24-day multicrossover model (MCOM) including six treatment periods and five regular interchanges between pancreatic enzymes and placebo. The evaluation was based on a comparison of the enzyme- and placebo-associated symptoms and on the number of times pancreatic enzymes were associated with less symptoms than the preceding or following placebo period in individual patients. No evidence of a short-term effect of pancreatic enzymes in NUD was found. PMID- 2320951 TI - Structural analyses of human developmentally regulated Vh3 genes. AB - In mice, a restricted set of the Jh-proximal Vh genes are preferentially expressed during early ontogeny. Recently, analyses of human Ig cDNA from a fetal liver revealed a restricted set of Vh genes which belong to the Vh1, 3, 4, and 6 families. Although the Vh6 and some Vh5 genes are proximal to the Jh region, no Vh5 gene was found in the fetal liver, suggesting that the distance between the Jh genes and some early-expressed Vh genes may not be the only factor responsible for Vh gene expression during early development. As an initial step in searching for other underlying mechanisms, we characterized two human germline Vh3 genes which belong to the developmentally restricted Vh repertoire, and found that they contain many enhancer-like sequences which are identical, or highly homologous to, various transcriptional enhancer motifs. Hence, it is conceivable that, in addition to the established positional effects, cis regulatory elements may be important in the programmed expression of some Vh genes during early B-lymphocyte development. PMID- 2320952 TI - Ciclosporin-dependent, nu-independent, mucosal interleukin 6 response to gram negative bacteria. AB - Regulation of the mucosal inflammatory response to Gram-negative bacteria was analysed. The interleukin 6 (IL-6) secretion, influx of polymorphonuclear leucocytes into urine, and bacterial clearance from the kidneys were compared between Balb/c (nu/nu) and nu/+/- mice, with and without ciclosporin (CsA) treatment. There was no significant influence of the nu genotype on any of the host responses measured. CsA pretreatment significantly decreased Il-6 secretion in both nu/nu and nu/+/- mice, but did not affect bacterial clearance or the leucocyte response in any mouse strain tested. Tissue damage, in addition to bacterial infection, resulted in significantly higher levels of IL-6 than bacterial infection alone. Tissue-damaged mice were significantly less likely to clear the bacterial infection than their non-damaged counterparts, but there was no significant difference in the leucocyte response. CsA pretreatment did not significantly reduce the levels of IL-6 in the tissue-damaged mice. These results demonstrate that the mucosal inflammatory response to Gram-negative infection, including IL-6 secretion, is nu-independent, and that bacterial infection alone or in combination with tissue damage induce IL-6 secretion by two different pathways. PMID- 2320953 TI - Human peripheral blood-derived dendritic cells do not produce interleukin 1 alpha, interleukin 1 beta, or interleukin 6. AB - Little is known about the non-antigen-specific signals delivered to T cells by dendritic cells (DC). Because several monocyte-derived factors like interleukins 1 alpha, 1 beta, and 6 (IL-1 alpha, IL-1 beta, and IL-6) enhance the T-cell proliferative responses, we studied the production of the above-mentioned cytokines by DC separated from human peripheral blood. The intracellular expression of the proteins (IL-1 alpha and IL-6) was studied at a single-cell level using an immunolabelling technique. The supernatants and cell lysates were studied with ELISA (IL-1 alpha and IL-1 beta). Northern blotting analysis was used to quantitate the mRNA levels. Several approaches were taken to stimulate the production of IL-1 alpha, IL-1 beta, and IL-6 by DC. These included the incubation of the DC in the presence of either LPS, rIL-1, or monoclonal anti-HLA DR antibody, or the stimulation of cells with resting allogeneic T cells. None of the stimuli was able to induce the production of IL-1 alpha, IL-1 beta, or IL-6 by DC, whereas LPS-stimulated monocytes were strong producers of these mentioned cytokines and expressed the respective mRNA. Thus we concluded that IL-1 alpha, IL-1 beta, and IL-6 are primarily monocyte-derived factors and that these factors are not needed or produced during the activation of resting T cells by DC. PMID- 2320954 TI - Activation of human T lymphocytes by phorbol-12,13-dibutyrate and ionomycin. AB - The calcium ionophore ionomycin and the phorbol ester phorbol-12,13-dibutyrate (PDBu) are shown to have a synergistic effect upon interleukin 2 (IL-2) production, interleukin 2 receptor expression, and T-lymphocyte proliferation. The proliferative response was inhibited by addition of a monoclonal antibody directed against the IL-2R (Tac antigen) demonstrating that PDBu and ionomycin induce T-cell growth through an IL-2-dependent autocrine pathway. Sequential stimulation with PDBu and ionomycin failed to induce IL-2 production, IL-2R expression, and consequently proliferation of the T cells, indicating that T-cell activation requires simultaneous activation of protein kinase C (PKC) and elevation of cytosolic calcium. Exposure of T cells to both agents for different times resulted in IL-2 production, IL-2R expression, and proliferation in proportion to the duration of incubation with at least 4 h required for maximal T cell activation. Further, in the presence of PDBu maximal T-cell activation was found to require stimulation with ionomycin for 4 h, indicating that a sustained increase in free cytoplasmic calcium of several hours' duration is essential for T-cell activation. In contrast T cells incubated with ionomycin were induced to produce IL-2 and express IL-2Rs upon brief exposure to PDBu with a 2-h incubation period being sufficient for maximal T-cell activation. Thus transient activation of PKC seems to be sufficient for activation of the IL-2 gene and IL-2R gene. However, maximal T-cell activation requires activation of PKC for at least 2 h. PMID- 2320955 TI - Low T- and B-cell reactivity is an apparently paradoxical request for murine immunoprotection against Streptococcus mutans. Murine protection can be achieved by immunization against a B-cell mitogen produced by these bacteria. AB - C57BL/6 mice thymectomized as adults or depleted of CD4+ cells were much less susceptible than intact conventional mice to the B-cell mitogenic and specific immunosuppressive effects of a protein designated as F5'EP-Sm secreted by Streptococcus mutans. These mice were also considerably more resistant to infection by these bacteria than intact individuals. The immunosuppressor effect of F5'EP-Sm was also abrogated, however, in conventional intact mice when immunized intraperitoneally against heat-inactivated F5'EP-Sm. On the other hand, resistance to bacterial infection could be achieved by immunization of conventional intact C57BL/6 mice against heat-inactivated F5'EP-Sm by intraperitoneal or intradermal routes even when the animals were infected 3 months after immunization and even when the immunization procedure did not include Freund's adjuvant, which was the case with the intradermal route. Interestingly, the protection against the bacterial infection was accompanied by only a minor increase in specific serum antibodies against F5'EP-Sm. These results are discussed in the context of adequate strategies for immunoprotection against Streptococcus mutans and other micro-organisms which are secretors of substances that share both B-cell mitogenic and immunosuppressive properties and which are thus able to suppress the immune response by overstimulation of the immune system of the host. PMID- 2320956 TI - Fine specificity and isotype expression of anti-PC antibodies in BALB/c, MRL/Mp lpr/lpr, and -(+)/+ mice at different ages. AB - The MRL/Mp congenic mouse strains develop autoimmune disease with age. We have investigated age- and autoimmune-related changes in fine specificity, isotype spectra and T15 idiotype expression of the anti-phosphorylcholine (PC) response in BALB/c, MRL/Mp- + and -lpr congenic mice and in (BALB/c x MRL/Mp-lpr) F1 hybrids. Two groups of anti-PC antibodies with distinct fine specificity are elicited in the memory response. Group I antibodies recognize the PC moiety and express the T15 idiotype. Antibodies of group II are specific for phenyl phosphorylcholine and are found predominantly in the memory response. In the MRL/Mp-lpr and - + strains only a minor population of antibodies expresses the T15 idiotype at all ages. However, a third group of antibodies was observed which binds to PC-coated proteins and to Diplococcus pneumoniae R-36A. This binding was not inhibited by PC-chloride and appeared mainly in the memory response at old age. The isotype distribution among anti-PC antibodies was similar in all strains analysed. In the initial response primarily mu, gamma 3 and gamma 1 isotypes were produced, while in the memory response gamma 1 was dominant. Thus autoimmune defects and ageing result in altered anti-PC antibody and idiotype profile, probably related to altered states in both the T- and B-cell compartments. PMID- 2320957 TI - Meningoencephalitis with septic intracerebral infarction: a new feature of CNS listeriosis. AB - The broad spectrum of CNS listeriosis is expanded by the observation of an intracerebral infarction associated with meningoencephalitis. Sequential CCT scans in a 66-year-old immuno-compromised woman led to the clinical diagnosis of brain abscess. Autopsy revealed an infected intracerebral infarction most probably due to temporal occlusion of the middle cerebral artery by septic microemboli or septic endothelial damage. PMID- 2320958 TI - Interleukin-1 production in bacterial meningitis. AB - Interleukin-1 (IL-1) is the key initiator of host responses to infection. We describe here the lipopolysaccharide-(LPS) (20 micrograms/ml) stimulated IL-1 production of peripheral blood monocytes in 2 children with Haemophilus influenzae meningitis. We found a depressed IL-1 production at the acute stage of the infection when the meningitis was most active with return to normal coinciding with clinical recovery. These results show an inverse correlation with acute phase reactants and IL-1 production. Normalization of IL-1 production seems to be a good prognostic sign in bacterial meningitis. PMID- 2320959 TI - Recurrent encephalitis due to trimethoprim intake. AB - We wish to report a 76-year-old woman with 2 episodes of meningitis related to the intake of trimethoprim. On both occasions the patient demonstrated encephalitic symptoms and a pathological electroencephalogram with cerebral function disturbances. A similar case with encephalitic symptoms due to trimethoprim has not been reported earlier. PMID- 2320960 TI - Bacterial meningitis with "normal" cerebrospinal fluid in adults: a report on five cases. AB - Five adult patients with bacterial meningitis and normal cerebrospinal fluid (CSF) findings are described. All were patients in whom the lumbar puncture was performed very early in the course of the disease, or who had a low white blood cell count in peripheral blood. In such cases the diagnosis of bacterial meningitis may be overlooked. PMID- 2320961 TI - The prevalence of IgG antibodies to spotted-fever group rickettsiae among urban and rural dwelling children in southern Israel. AB - The prevalence of IgG antibodies to spotted-fever group rickettsiae was studied in a sample of 1,055 healthy children aged 2-17 years, residents of the desert Negev region of southern Israel. Groups of children from 5 different places of residency were tested: (1) urban children from the city of Beer-Sheva; (2) children from Omer, a suburb of the city; (3) children from rural communes ("kibbutz"); (4) children from small agricultural settlements ("moshav"); and (5) seminomadic bedouin children. Overall 40 sera (3.8%) were positive by the indirect immunofluorescent antibody assay at a titer of 40. The prevalence rate was 3.6% in males and 4.0% in females. Age-specific prevalence rates for the 2-5, 6-9, 10-13 and 14-17 year old groups were 2.0, 5.4, 4.1 and 3.6% respectively. The prevalence rates by place of residency were: urban 3.3%, suburban 3.3%, "kibbutz" 3.8%, "moshav" 5.1% and seminomadic children 3.3%, and did not differ by socio-economic status as measured by degree of crowding. The results indicate that spotted fever is endemic in all human habitats in the Negev region. Our data do not support association to sex or socio-economic status of the children tested. Lack of cumulative prevalence rates with increasing age suggests that antibodies may wane to undetectable levels in the years following the infection. PMID- 2320963 TI - Persistent excretion of Salmonella in foreign-born adopted and native Swedish children. AB - The duration of salmonella excretion in 162 foreign-born adopted children and 132 native Swedish children was studied. Of the adopted children (96% being less than 1 year of age) 54% still excreted salmonella at 12 weeks, 32% at 6 months, and 12% at 1 year after arrival in Sweden. The carrier state was more prolonged in the age group 0-3 months compared to the age group greater than 6 months. In the group of native Swedish children, aged 0-5 years, 18% still excreted salmonella at 12 weeks, 4% at 6 months, and none at 1 year after the gastroenteritis episode. A majority of these children were older than 1 year. Intrafamilial transmission of salmonella seemed to be uncommon. Only 6% of the adopted children infected another family member. PMID- 2320962 TI - Complement and immunoglobulin studies in 15 cases of chronic meningococcemia: properdin deficiency and hypoimmunoglobulinemia. AB - The purpose of this study was to investigate whether patients with chronic meningococcemia have abnormalities in their humoral immune system. The alternative and classical complement system, the levels of IgA, IgG and IgM, as well as IgG subclasses were studied in 15 individuals who had recovered from chronic meningococcemia. We found one individual with complete deficiency of properdin, a component of the alternative complement pathway. In the other patients, the complement system was normal. The mean plasma IgG concentration was significantly below normal in the patient group, while the mean values of IgA, IgM and the IgG subclasses were normal. Two individuals, however, had low IgG2 and IgG4 levels. We conclude that properdin deficiency and reduced plasma IgG levels may predispose to chronic meningococcal disease, but that the majority of patients with chronic meningococcemia have a normal humoral immune system. PMID- 2320964 TI - Audit of decision-making regarding female genitourinary infections in outpatient practice. AB - Patient data, diagnosis, work-up measures, and prescriptions were collected from 63 consultations by general practitioners (GPs) to study day-to-day management of women with complaints suggestive of genitourinary (GU) infections. The collected patient data were thereafter presented to a panel of 9 specialist physicians for their individual recommendations. On drug prescriptions, the panel supported 81% of the decisions, did not support 14%, and remained undecided on 5% of the cases. In all but one of the unsupported cases, the GP had prescribed antibiotics. On diagnoses, the panel supported 62% of the decisions, did not support 13%, and was undecided on 25% of the cases. The most frequent discordance concerned diagnosis of urethritis. On collection of medical data by history and physical examination, the panel found 22% of the consultations unsatisfactory. Discordance in both diagnosis and drug prescription were related to remarks about data collection. The results suggest that the body of knowledge available for GPs for management of female GU infections in outpatient practice is incomplete. PMID- 2320965 TI - Incidence of tick-bite in man in Aland Islands: reference to the spread of Lyme borreliosis. AB - The common tick Ixodes ricinus is a vector both for the virus of tick-borne viral encephalitis (Kumlinge disease, KD) and of Borrelia burgdorferi (Lyme borreliosis, LB). Bites of the tick are believed to be common in Aland, an island province of Finland in the Baltic Sea. KD has been seen there for many years, and cases of LB have been diagnosed lately. The purpose of this study was to find the incidence of tick-bite among the population with possible implications for the spread of LB. A questionnaire was sent to 561 persons greater than 8 years of age out of a total of 21,281 in order to record tick-bites and erythema chronicum migrans (ECM). The number of answers was 519 (92.5%). 441 persons (85%) had been bitten by ticks, 146 greater than 10 times. 14 probands had had ECM, 73 other rashes around the tick-bite. It is concluded that tick-bites are very common among the population, and thus conditions are favourable for the spread of any tick-borne infection such as LB. The number of patients with secondary or tertiary LB diagnosed in the area is presently 17. It is likely that there are many undetected cases in the area. PMID- 2320967 TI - Isolation of respiratory syncytial virus from liver tissue and extrahepatic biliary atresia material. AB - Respiratory syncytial virus (RSV) was isolated from liver tissue in a 7-month-old infant with extrahepatic biliary atresia. To our knowledge this is the first report of RSV isolation from human liver tissue. PMID- 2320966 TI - Severe respiratory syncytial virus pneumonia in an adult renal transplant recipient: successful treatment with ribavirin. AB - Respiratory syncytial virus (RSV) pneumonia may be a severe disease especially in immunocompromised patients. It is quite rare in adults. We report a case of severe RSV pneumonia in a 38-year-old male renal transplant recipient with successful outcome after ribavirin aerosol therapy. PMID- 2320968 TI - A case of tularemia meningitis in Sweden. AB - Tularemia meningitis occurred in a previously healthy 64-year-old man from Northern Sweden. The patient was immunocompetent and recovered without sequelae. The bacterial isolate conformed by most criteria with the Euro-Asian biovar Francisella tularensis var. palaearctica. Tularemia meningitis may mimic meningitis caused by Mycobacterium tuberculosis. PMID- 2320969 TI - Histological versus stereological methods applied at spermatogonia during normal human development. AB - The number of spermatogonia per tubular transverse section (S/T), and the percentage of seminiferous tubulus containing spermatogonia (the fertility index (FI] were measured in 40 pairs of normal autopsy testes aged 28 weeks of gestation-40 years. S/T and FI showed similar changes during the whole period, and were minimal between 1 and 4 years. The number of spermatogonia per testis (S/testis) and the number of spermatogonia per cm3 testis tissue (S/cm3) were estimated by stereological methods in the same testes. S/T and FI respectively were significantly correlated both to S/testis and S/cm3. So quantification of spermatogonia by S/T or FI measurement is a reasonable alternative to stereological examinations. PMID- 2320970 TI - Upper urinary tract deterioration after implantation of artificial urinary sphincter. AB - The preoperative urodynamic evaluations of twenty patients with myelomeningocele who had had artificial sphincter implantation because of urinary incontinence were reviewed. Four patients developed hydronephrosis and severe impairment of renal function between two and six years after implantation of the artificial sphincter. The condition was partly reversible after removal of the artificial sphincter. The urodynamic evaluation prior to implantation revealed in the four mentioned patients compared to the 16 patients with normal upper urinary tract, a tendency to lower bladder compliance, lower bladder capacity and more severe detrusor hyperreflexia, but it was not possible to make a clear discrimination between the two groups. Attention is drawn to this unfortunate combination of effects after artificial sphincter implantation. Periodic control of the upper urinary tract by urography is recommended. PMID- 2320971 TI - Volume corrected mitotic index (M/V index) in human bladder cancer; relation to histological grade (WHO), clinical stage (UICC) and prognosis. AB - A retrospective study was performed on 83 bladder cancer patients diagnosed at the Department of Surgery, Kuopio University Central Hospital, during the years 1965-1987. The follow-up time was 22 years, and the mean follow-up time of individual patients was 13 years (range 9.4-22 years). Histological grade (WHO), volume corrected mitotic index (M/V index) and clinical stage (UICC) were correlated to the survival of patients. Histological grade, M/V index and clinical stage were associated with crude survival (all causes of death included) with little predictive power. The recurrence of the disease could be predicted by the M/V index, but not by histological grade or clinical stage. When bladder cancer deaths only were included, histological grade (chi 2 = 26.6, p less than 0.001), M/V index (chi 2 = 6.6, p = 0.042) and clinical stage (chi 2 = 31.7, p less than 0.001) were clearly associated with prognosis. Also the metastasizing potential of bladder carcinomas could be predicted by the M/V index and by the histological grade at the time of primary diagnosis. Histological grade and M/V index were positively correlated (chi 2 = 16.7, p = 0.002, r = 0.47). In multivariate analysis clinical stage, histological grade and M/V index predicted prognosis in the order of importance. PMID- 2320972 TI - Effects of variations in extracellular pH on spontaneous contractile activity and response to nerve stimulation in smooth muscle from rat urinary bladder. AB - The effects of variations in extracellular pH have been studied on rat detrusor muscle in vitro. At pH 7.4 a continuous low amplitude spontaneous contractile activity was found. At pH 6.75 the contractions became more regular with periods of relaxation between the contractions which had increased in amplitude. At pH 7.85 the reverse was found. The results are interpreted as a membrane effect of pH. No effect of pH on amplitudes of high-K(+)-induced contractures was found. Carbachol dose-response relations and maximal contraction amplitude to carbachol was similar at pH 7.4 and 6.75. A significant depression in response to nerve stimulation was, however, noted at pH 6.75. We suggest that, while the force output of the activated detrusor smooth muscle cell is unaffected by changes in extracellular pH, a prejunctional inhibition of nerve induced contraction might occur at low pH. PMID- 2320973 TI - Hope for successful xenografting by immunosuppression with monoclonal antibody against CD4, total lymphoid irradiation and cyclosporine. Six months' survival of hamster heart transplanted into rat. AB - Hamster hearts were transplanted to rats, and the effects of combinations of total lymphoid irradiation (TLI), cyclophosphamide, cyclosporine A (CyA) and monoclonal antibodies (MAB) were investigated. Controls not immunosuppressed rejected their xenograft in 3 to 5 days, while combination immunosuppression including MABs against CD4 or IL-2-receptors extended graft survival significantly. In one case, the graft was still functioning 180 days after transplantation, which is the longest survival seen in this model. The use of specific MABs may open a new era for both xeno- and allo-transplantation. PMID- 2320974 TI - Extracorporeal shock wave lithotripsy of a kidney stone complicated with Candida albicans septicaemia and endophthalmitis. Case report. AB - Following a routine extracorporeal shock wave lithotripsy of a kidney stone, candida septicaemia and eight days later candida endophthalmitis developed. PMID- 2320975 TI - Sudden infant death syndrome during weekends and holidays in Norway in 1967-1985. AB - A few previous studies have revealed an increased risk for sudden infant death syndrome (SIDS) during weekends and holidays suggesting environmental factors as potential trigger mechanisms for death. In the present study, the weekend/holiday effect has been assessed on the basis of 1480 SIDS cases in 19 Norwegian counties during a 19-year period (1967-85). The phenomenon has been confirmed for 17 of the 19 counties. Special attention has been attached to differences in the geographical and seasonal distribution of the phenomenon. Deaths of other causes in infancy did not display such a dependency on the day of the week. PMID- 2320976 TI - Parents' response to recurrent middle ear infection in their children. AB - Recurrent ear infection in children during pre-school years is an important public health problem. Common advice given to parents is to minimize exposure of susceptible children to crowding and air pollution. This study aimed at investigating what changes parents undertake to improve the health of an otitis prone child. Parents of children with greater than or equal to 5 events before age thirty months (index children; n = 198) and a matched control group (n = 396) were asked to fill in a questionnaire. Results show that 22.3% of index-families and 9.5% (p less than 0.001) of control families had changed one or more of the following conditions: working hours, child day-care, housing and smoking habits. In summary, index families and control families were remarkably similar given the striking difference in otitis media, a finding that rises concern. PMID- 2320978 TI - Present and projected consumption of hospital bed-days as a function of terminal days before death. AB - In 1983 the bed-day consumption per year per 1,000 inhabitants was 1,571 for all subjects in the Copenhagen County, and 774, 1,239, and 4,918 for subjects 0-19 years, 20-64 years, and above 65 years of age, respectively. Extrapolating from these data the hospital bed-day consumption per inhabitant is predicted to increase by 20.6% in Denmark by the year 2025 as compared to 1986. The mean hospital bed-day consumption per subject during the last 150 days prior to death in hospital was 25.0 days for males and 29.7 for females. Making the conservative assumption that only subjects who die in hospital consume hospital bed-days during the last 150 days before death, the bed-day consumption during 1983 of 0 64 years old subjects being in the terminal 150-day phase was 5.87% of the total annual bed-day consumption of this age group. For subjects 65 years of age or older, it was 18.1%. PMID- 2320977 TI - Services to families with children. A study of community work in Uppsala. AB - This article describes some of the results of a study of services to families and children in a suburban district, Sweden. Services included in the study were: maternal and child health care, child psychiatry, services for handicapped children, school health care, day care services, community social services and family counselling services. The baseline studies comprised analyses of official goals expressed in legislation and recommendations, interviews with local politicians and administrators, record studies, studies of working time distribution and questionnaires to field professionals and families. The results indicate that services with traditional goals and well-defined tasks (e.g. health supervision) were more satisfied with their goal attainment, less inclined to collaborate with other services, and more occupied with direct client work than services with non-traditional goals and vaguely defined tasks (e.g. strengthening democracy). PMID- 2320979 TI - Prevalence of sexual abuse history in a random sample of Norwegian women. AB - In order to obtain an estimate of the prevalence of sexual abuse history among adult women, data from a gynecological interview of a random sample of 118 women aged between 20-49 were analysed. Childhood sexual abuse involving genital contact was reported by 8.5% of the women. Intrafamilial sexual abuse in childhood was reported by 7%, 10% of all women who had ever lived in a relationship reported sexual abuse by a violent spouse, additionally 7% had experienced sexual abuse by a non-violent spouse. 5% of all women had experienced adult sexual abuse by other than their spouse. Sexual abuse in childhood and by violent spouse was associated with a history of psychological problems and of suicidal ideation or attempts. PMID- 2320980 TI - Quality of life: concept and assessment. AB - To understand and assess the concept "quality of life", it must be analyzed. In this report it is postulated that quality of life covers life as a whole as well as different subdomains of life. Life quality is defined as perceived global satisfaction and satisfaction within a number of key domains with special emphasis on well-being. A comprehensive chart of relevant life domains is presented and a flexible package of tested rating techniques outlined. In order to obtain valid and sensitive assessments, pincer operations with various types of ratings are recommended. PMID- 2320981 TI - Cannabis and mortality among young men: a longitudinal study of Swedish conscripts. AB - The association between level of cannabis consumption and mortality during a 15 year follow-up was studied in a cohort of 45,540 Swedish conscripts. The relative risk of death among high consumers of cannabis (use on more than 50 occasions) was 2.8 (95% confidence interval (1.9-4.1)) compared with non-users. However, after control for social background variables in a multivariate model, no excess mortality was found. A high level of consumption of other drugs was also associated with increased mortality; the relative risk of high consumption (greater than 50 times) was 4.6 (2.4-8.5) compared with non-users. After adjustment for social background a relative risk of 1.2 (0.8-1.9) remained; for those having used drugs intravenously more than once, the relative risk was 1.6 (0.9-2.7). Among causes of death a strong predominance was found for violent death, suicide or uncertain suicide being the single most important accounting for 34.4% of all deaths. The proportion of suicides increased sharply with the level of cannabis consumption. PMID- 2320982 TI - [Anabolics and sports]. AB - Anabolics (anabolic steroids and, in recent years, recombinant human growth hormone) are used to enhance athletic performance. Although there is no definite proof of a performance enhancing effect of anabolic steroids (ethical difficulties and blinding problems with high dose steroid treatment), evidence suggests that steroids may increase muscular strength in some subgroups of athletes. Unfortunately, numerous side effects and (in some cases at any rate) permanent damage may occur as a consequence of abuse of anabolics. This is chiefly the case in adolescents and women. As long as athletes and their trainers believe in the efficacy of anabolics, and no mandatory testing in the training periods is imposed, the abuse of anabolics by athletes will distort fair competition in sport. PMID- 2320983 TI - [Swiss Society for Pneumology. Annual meeting. Basel, 26-28 April 1990. Abstracts]. PMID- 2320984 TI - [Switzerland-the European Community: recognition of the higher-education diploma]. PMID- 2320985 TI - [The cleaning effect of different root canal instruments. A semiquantitative comparative study]. AB - The efficacy of various root canal cleaning instruments was evaluated in this in vitro study. 60 freshly extracted teeth were divided into 6 groups of 10 teeth each. The root canals of the teeth were cleaned with hand-instruments, sonic instruments (Sonic Air 3000 and Endostar 5), mechanical instruments (Canalfinder System), and ultrasonic instruments (Cavi-Endo with or without integrated rinsing) according to the manufacturer's instructions. The canals were then examined in a SEM at 60 selected points to assess the presence or absence of smear layer, dentin chips, and cellular remnants. The smoothness of the canal walls was also evaluated. Similar amounts of tissue remnants were scored by the SEM method. None of the instruments tested were able to produce debris-free specimens. The Cavi-Endo, Endostar 5, Sonic Air 3000, and the hand-instruments yielded similar scores. However, the Endostar 5 cleaned the canals quicker and with fewer problems than the other instruments. The efficacy of the integrated rinsing in the Cavi-Endo must be questioned. The smear layer was somewhat reduced by the Cavi-Endo, using a syringe and needle, but without the integrated spray. The Canalfinder System produced poorer cleaning scores but they were not significantly different from the other instruments' scores. PMID- 2320986 TI - [Anomalies in the number of permanent teeth in orthodontic patients in 2 localities in Croatia]. AB - The authors investigated the frequency of anomalies among permanent teeth in two regions in Yugoslavia--Istria and Slavonia--in a group of 4449 orthodontic patients (1890 boys and 2559 girls, age 6-18 years; in Istria: 1060 boys and 1341 girls, in Slavonia: 830 boys and 1218 girls). The anomalies were diagnosed by clinical examination and by orthopantomogram analysis. The anomalies were significantly more frequent in children of Istria compared to the ones of Slavonia, i.e. hypodontia was found in 6.25% versus 2.34% and hyperdontia in 1.37% versus 0.63%. Hypodontia in the mandible prevailed among the children in Istria while that in the maxilla among the children in Slavonia. The differences in the sequence of the hypodontia frequency for each tooth in both sexes have been established separately for the two regions. PMID- 2320987 TI - [Dentistry in old age. Care for the occupants of old age homes]. PMID- 2320988 TI - [Enlargement of the transverse diameter of the pelvis in a cat]. AB - By symphysiotomy and inserting of a homograft, the pelvic transverse diameter of a cat, suffering from pelvic fracture complication, has been improved. Chronic obstipation has been suppressed; gait and muscular atrophy have been ameliorated. PMID- 2320989 TI - [The uterine motility of cattle during late pregnancy, labor and puerperium. I. Spontaneous motility]. AB - In the present study spontaneous uterine motility was recorded in 4 cows during late pregnancy, parturition and the puerperium using pressure microsensors and electrodes which were surgically implanted into the myometrium of the pregnant horn 3 to 4 weeks before parturition. Hysterograms were evaluated by means of pressure amplitude, frequency, duration, interval of uterine contractions and also by electromyography. During the last 2-3 weeks of pregnancy only single weak uterine contractions of different intensity were seen. About 18-20 hours a.p. frequency and amplitude of mainly tubocervical directed waves continuously increased. When the fetus entered the birth canal and especially during expulsion of the calf extremely strong irregular contractions occurred, which became very regular during the first hours p. p. After the placenta has been released 3-8 hours p. p., spontaneous uterine motility drastically decreased until the second postpartal week, when it started to increase again. PMID- 2320990 TI - [Hypertrophic gastropathy similar to Menetrier's disease in pigs slaughtered in accordance with regulations]. AB - The authors found during a study concerning the gastric pathology in pigs 2828 cases of hypertrophic gastropathy in 8408 regularly slaughtered animals. After a description of the morphologic patterns of the lesions, the authors make some pathogenetic hypothesis and conclude that this lesion is like Menetrier's disease of man. PMID- 2320991 TI - Research as a tool for practice: adapting the Q-sort research method to patient education. PMID- 2320992 TI - Standardized nursing care plans for acute care SCI: improved documentation. AB - Adequate documentation of spinal cord injury (SCI) nursing care is necessary for evaluation of patient progress and compliance with standards of care. The objective criteria used to evaluate nursing care include the nursing data base, the care plan, and the nurses' notes. The nursing care plan reflects the needs of the SCI client and is the basis from which documentation about these needs arises. Standards for acute care SCI nursing were recently developed for the 10 designated SCI centers in Florida. To improve the documentation of these standards, neuroscience nurses at Shands Hospital developed standardized care plans that can be individualized for each SCI client. The implementation of these care plans improved documentation of the standards for acute care SCI nursing. Additional benefits included an increased awareness of the nursing diagnoses among staff nurses and improved equality of care for the SCI client. PMID- 2320993 TI - Implementation of standards of practice: a spinal cord injury program. AB - Developing and implementing standards of spinal cord injury nursing practice is an essential component of a program for evaluating and ensuring quality patient care. A comprehensive program for monitoring SCI nursing care as developed at the James A. Haley Veterans Hospital is described. Over a 12-month period, nursing staff utilized standards of practice to assure attainment of expected patient outcomes and increased staff involvement in the SCI quality assurance program. Evaluation of the task force project provides implications for use in other nursing practice settings. PMID- 2320994 TI - [Possibilities of sonography in patellar apex syndrome]. AB - 23 Patients suffering from jumper's knee were examined by sonography. Using ultrasound imaging, we demonstrated pathologic changes in the tendon. Reproducible documentation of the patella tendon was proved by using three specimens. In a control group of 110 normal objects normative values for the size and structure of the tendon were documented. We present a classification using ultrasound patterns. With this classification the diagnosis becomes objective and reproducible. The physician can decide which conservative therapy is appropriate to this state of the disease, the surgeon gets information for the operation, and the success of the therapy can be documented. PMID- 2320995 TI - Interrelationship between the concentrations of some elements in the organs of Japanese with special reference to selenium-heavy metal relationships. AB - Multi-element analyses were conducted on internal organs (cerebrum, cerebellum, heart, spleen, liver and kidney) of Japanese obtained from 45 forensic medical autopsy cadavers. Elements analyzed and analytical methods were as follows: Ca, Cd, Cu, Fe, K, Mg, Na, P and Zn by inductively coupled plasma atomic emission spectrometry; total Hg (T-Hg) and inorganic Hg (I-Hg) by cold vapour atomic absorption spectrometry; methyl Hg (MeHg) by gas chromatography; and Se by fluorometry. A significantly positive correlation between Se and T-Hg was observed in kidney, liver, heart and spleen. The T-Hg/Se molar ratio was less than 1 in all the organs examined. The correlation between Zn and Cd was significant in liver and kidney. Multiple regression analyses using Se as a dependent and I-Hg, MeHg, Zn, Cd, Cu as independent variables were conducted on each organ. Inorganic Hg was a significant independent variable in kidney, whereas in liver and spleen it was MeHg. Cadmium was significant in explaining the variations in Se in liver and kidney medulla, indicating Cd-Se co accumulation in humans. PMID- 2320996 TI - The nutritional selenium status of healthy Greeks. AB - The nutritional selenium status of apparently healthy Greeks has been assessed by measuring fluorimetrically the selenium content of whole blood, morning urine, hair and finger nails. The means and standard deviations were 165 +/- 33, 25 +/- 7 ng Se ml-1, 416 +/- 86, and 536 +/- 91 ng Se g-1, respectively. No significant difference was found between the selenium content of whole blood, hair and finger nails, but, for morning urine, there was a significant difference between males and females. The young and the elderly have less selenium in these biological materials than other Greeks. Whole blood selenium correlates significantly with morning urine, hair, and finger nail selenium, as does hair and nail selenium of male, female and male + female Greeks. The results are compared with those in the literature and possible explanations for the observations are presented. It is concluded that the selenium status of Greeks is satisfactory. PMID- 2320997 TI - Study on the relation of Se, Mn, Fe, Sr, Pb, Zn, Cu, and Ca to liver cancer mortality from analysis of scalp hair. AB - This project made use of Chongming Island, a high prevalence area for liver cancer, with an uneven geographical distribution, to study the relation between trace elements and high liver cancer incidence. A comparative study of Se, Mn, Fe, Sr, Pb, Zn, Cu and Ca contents of scalp hair of normal persons living in areas with different incidences of liver cancer, and a case-control investigation matched with sex and age were made. The selenium level is relatively low compared with other locations in China, which might indicate Se deficiency on the island. Iron and Mn show an obvious difference, indicating that the availability of these elements was less in the high cancer incidence part of the island than in the low incidence part. The hair iron content of patients with liver cancer is clearly lower than that of normal controls. Selenium, Mn and Fe should be taken into consideration in liver cancer prevention research. PMID- 2320998 TI - The accumulation of cadmium by vegetables grown on soils contaminated from a variety of sources. AB - The accumulation of cadmium by four crops (cabbage, carrot, lettuce and radish) grown on soils contaminated from a variety of sources was investigated in greenhouse pot experiments. Stepwise multiple regression analyses of the data revealed that, out of the 23 soil variables determined, only eight were significantly related to cadmium accumulation in the edible plant tissues. The most frequently occurring soil parameter was total cadmium, which was inversely related to plant cadmium accumulation (CdPlant tissue/CdSoil). This implies that, for the heterogeneous group of soils used, as the concentration of cadmium in the soil increases the proportion available to the plant decreases. This may be due to the presence of metallic ore particles and/or the high sorptive capacity of the most contaminated soils. When the data were divided into two groups: sewage sludge amended soils and inorganically contaminated soils, the R-squared values were usually enhanced and some differences occurred in the variables included in the multiple regression equations; this may be indicative of the differences in speciation. Cadmium accumulation by plants grown on sewage sludge amended soils was lower than that for the inorganically contaminated soils. The heterogeneity of the inorganically contaminated group of soils resulted in lower R-squared values for the multiple regression equations; this group of soils exhibited a wide range of soil variables, such as pH, and had been contaminated by a variety of means, such as atmospheric deposition from metal smelters and the dumping of mine wastes. PMID- 2320999 TI - Chamber testing of organic emission from building and furnishing materials. AB - The equipment and the procedure employed for the qualitative and quantitative determination of the volatile organic compounds emitted from samples of building and furnishing materials are described. The equipment includes two small test chambers (0.45 m3), with accurately controlled temperature, relative humidity and air flow rate, and instrumentation for sampling and analysis (Tenax tubes, GC-FID and GC-MS). To find quasi-steady-state emission conditions, the procedure includes the determination of the time profiles of the organic compounds concentration, which develop after the introduction of the samples into the chamber. A best-fitting, double exponential equation is used for this purpose. The procedure has been applied to three materials: particle board with carpet; gypsum board with wallpaper; and plywood with polyurethane lacquer, for which the steady-state emission factors (mg m-2 h-1) of several compounds are given. Many other compounds were identified, but were not quantified. Some comments are given on the health significance of the compounds emitted from the materials when used indoors. PMID- 2321000 TI - Hazardous petrol hydrocarbons from refuelling with and without vapour recovery. AB - Hydrocarbons in air were determined at pioneering European service stations equipped with vapour recovery systems. Vapour recovery was found capable of eliminating 99% of exposure during refuelling and greater than 95% of emissions to air. Vapour recovery is now being rapidly introduced at Swedish service stations as a result of demands concerning environmental and health hazards. The analytical technique used permitted samples corresponding to a single refuelling procedure to be analyzed. Sampling on an adsorbent tube was followed in the laboratory by thermal desorption and capillary gas chromatography. All prominent hydrocarbons were well separated on a methylsilicone phase. These include benzene and the alkenes of special interest with respect to health hazards. The particular importance of alkenes with respect to the formation of ozone and other photooxidants is discussed. The four isomeric butenes and the six isomeric pentenes were determined and found to constitute approximately 10% by weight of the petrol vapour. The highly reactive 2-alkenes were more abundant than the 1 alkenes. PMID- 2321001 TI - Cesium-137 in moose diet; considerations on intake and accumulation. AB - An attempt was made to estimate the daily intake of 137Cs by moose during different months and seasons, and to compare this result with the 137Cs activity concentration in moose muscles. Plants representative of moose diet in central Sweden showed a high 137Cs activity concentration compared with plants from agricultural systems, and there appears to be very slow reduction of 137Cs activity concentration in these forest plants. It seems that the daily intake of 137Cs was low during the summer, but it exhibited a peak in the autumn, which corresponds to the 137Cs activity concentration in moose muscles and also coincides with the hunting season. PMID- 2321002 TI - Examination and chemical treatment of industrial solid wastes for safe land application. I. Evaluation of toxic elements present in solid wastes from a fertilizer and chemical plant. AB - Four solid wastes from a fertilizer/chemical plant located in the area of Thessaloniki are examined using the U.S. Environmental Protection Agency's (EPA) extraction procedure for toxicity in order to determine their content of toxic elements. Analyses of the extracts indicate that one of the samples generates arsenic at a concentration which exceeds the EPA criterion level for this element by nearly 50 times. Another sample is characterised by pH values that are below the EPA minimum values; however, the toxic element concentration does not exceed EPA limits. The extractability of toxic elements from the solid wastes using various extracting solutions is also examined in order to determine the chemical conditions under which the toxic compounds are soluble. PMID- 2321003 TI - Grant financing: PI salaries. PMID- 2321004 TI - Who should study radiation effects? PMID- 2321005 TI - Stanford psychiatry deal falls through. PMID- 2321006 TI - Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. AB - The development and maintenance of the nervous system depends on proteins known as neurotrophic factors. Although the prototypical neurotrophic factor, nerve growth factor (NGF), has been intensively studied for decades, the discovery and characterization of additional such factors has been impeded by their low abundance. Sequence homologies between NGF and the recently cloned brain-derived neurotrophic factor (BDNF) were used to design a strategy that has now resulted in the cloning of a gene encoding a novel neurotrophic factor, termed neurotrophin-3 (NT-3). The distribution of NT-3 messenger RNA and its biological activity on a variety of neuronal populations clearly distinguish NT-3 from NGF and BDNF, and provide compelling evidence that NT-3 is an authentic neurotrophic factor that has its own characteristic role in vivo. PMID- 2321007 TI - Tumor cells exhibit deregulation of the cell cycle histone gene promoter factor HiNF-D. AB - Cell cycle-regulated gene expression is essential for normal cell growth and development and loss of stringent growth control is associated with the acquisition of the transformed phenotype. The selective synthesis of histone proteins during the S phase of the cell cycle is required to render cells competent for the ordered packaging of replicating DNA into chromatin. Regulation of H4 histone gene transcription requires the proliferation-specific promoter binding factor HiNF-D. In normal diploid cells, HiNF-D binding activity is regulated during the cell cycle; nuclear protein extracts prepared from normal cells in S phase contain distinct and measurable HiNF-D binding activity, while this activity is barely detectable in G1 phase cells. In contrast, in tumor derived or transformed cell lines, HiNF-D binding activity is constitutively elevated throughout the cell cycle and declines only with the onset of differentiation. The change from cell cycle-mediated to constitutive interaction of HiNF-D with the promoter of a cell growth-controlled gene is consistent with, and may be functionally related to, the loss of stringent cell growth regulation associated with neoplastic transformation. PMID- 2321008 TI - Engineering human prolactin to bind to the human growth hormone receptor. AB - A strategy of iterative site-directed mutagenesis and binding analysis was used to incorporate the receptor-binding determinants from human growth hormone (hGH) into the nonbinding homolog, human prolactin (hPRL). The complementary DNA for hPRL was cloned, expressed in Escherichia coli, and mutated to introduce sequentially those substitutions from hGH that were predicted by alanine-scanning mutagenesis and other studies to be most critical for binding to the hGH receptor from human liver. After seven rounds of site-specific mutagenesis, a variant of hPRL was obtained containing eight mutations with an association constant for the hGH receptor that was increased more than 10,000-fold. This hPRL variant binds one-sixth as strongly as wild-type hGH, but shares only 26 percent overall sequence identity with hGH. These studies show the feasibility of recruiting receptor-binding properties from distantly related and functionally divergent hormones and show that a detailed functional database can be used to guide the design of a protein-protein interface in the absence of direct structural information. PMID- 2321009 TI - Thymic epithelium tolerizes for histocompatibility antigens. AB - The role of thymic epithelium in the establishment of tissue tolerance was analyzed with a murine chimeric system. All T cells differentiated from birth onward in a thymus comprising allogeneic epithelium and syngeneic hematopoietic cells. Embryonic thymic rudiments that contained no hematopoietic cells from C3H (H-2k) donors were grafted to newborn athymic (nude) BALB/c (H-2d) mice. Chimeras that had normal T cell numbers and function rejected third-party skin grafts, but permanently accepted grafts syngeneic to the thymic epithelium. In vitro functional assays did not always correlate with the state of tolerance in vivo. Thus, pure thymic epithelium induces tolerance to histocompatibility antigens. PMID- 2321010 TI - Correction: copy numbers of HIV-1 RNA. AB - In Barbara J. Culliton's article "Gore Tex organoids and organoids and genetic drugs" (News & Comment, 10 Nov., p. 747), it should have been noted that the structural analysis of the implant connections, induding the micrographs shown on page 747, were performed by Christian C. Haudenschild at the Mallory Institute of Pathology, Boston University of Medicine, Boston, MA. His name should have been listed in the photo credit. The legend for the bottom photomicrograph should have read, "Below, a view in cross section confirms the presence of abundant vessels lined with endothelial cells and surrounded by several layers of smooth musclc cells. Two profiles without lumen resemble neural structures, but their precise identity remains to be investigated." PMID- 2321011 TI - Bacteria effective in Alaska cleanup. PMID- 2321013 TI - Dissecting the complex diseases. PMID- 2321012 TI - Imported monkey puzzle. PMID- 2321014 TI - Spontaneous order, evolution, and life. PMID- 2321015 TI - Population dynamics of the United States and the Soviet Union. AB - Population growth in the United States and the Soviet Union is slowing. Since the 1970s, labor force growth in both countries is slowing even more than population growth, and both countries are aging. Economic effects of slowing growth can be compensated for by increased participation in the labor force and increased productivity and by adjustments in the military forces. Economic flexibility and policy choices will determine how successfully the trend to slower population growth will be accommodated. PMID- 2321016 TI - Soft x-ray lasers and their applications. AB - The emerging technology of soft x-ray lasers has novel applications to microscopy, lithography, and other fields. This article describes the status of soft x-ray laser research with the aim of bringing the rapid developments in this field to the attention of potential users in other disciplines. The different techniques for generating a population inversion and producing a soft x-ray laser are reviewed. The status of current research in the field and the near-term prospects are described. It is expected that the range of potential applications of soft x-ray lasers will increase as their performance improves. Work aimed at increasing the output power and progressing to shorter wavelengths with these devices is also reviewed. PMID- 2321017 TI - A cellular automation model of excitable media including curvature and dispersion. AB - Excitable media are spatially distributed systems characterized by their ability to propagate signals undamped over long distances. Wave propagation in excitable media has been modeled extensively both by continuous partial differential equations and by discrete cellular automata. Cellular automata are desirable because of their intuitive appeal and efficient digital implementation, but until now they have not served as reliable models because they have lacked two essential properties of excitable media. First, traveling waves show dispersion, that is, the speed of wave propagation into a recovering region depends on the time elapsed since the preceding wave passed through that region. Second, wave speed depends on wave front curvature: curved waves travel with normal velocities noticeably different from the plane-wave velocity. These deficiencies of cellular automation models are remedied by revising the classical rules of the excitation and recovery processes. The revised model shows curvature and dispersion effects comparable to those of continuous models, it predicts rotating spiral wave solutions in quantitative accord with the theory of continuous excitable media, and it is parameterized so that the spatial step size of the automation can be adjusted for finer resolution of traveling waves. PMID- 2321018 TI - A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter. AB - Several mutants derived from transformed human B cell lines are defective in expressing major histocompatibility complex (MHC) class II genes. The failure to express a class II gene in at least one such mutant line has been mapped to the MHC class II X box, a conserved transcriptional element in the promoter region. A complementary DNA encoding a DNA-binding protein (human X box binding protein, hXBP-1) whose target is the human DR alpha X box and the 3' flanking region has now been cloned. This complementary DNA encoded a protein with structural similarities to the c-jun proto-oncogene product, and its target sequence was closely related to the palindromic target sequence of c-jun. Mutation of the hXBP 1 DNA target sequence decreased DR alpha promoter activity in vivo. These studies suggest that the hXBP-1 protein acts as a transcription factor in B cells. PMID- 2321019 TI - Limit of T cell tolerance to self proteins by peptide presentation. AB - Cytotoxic T lymphocytes (CTLs) recognize foreign peptides bound to major histocompatibility complex (MHC) class I molecules. MHC molecules can also bind endogenous self peptides, to which T cells are tolerant. Normal mice contained CTLs specific for self peptides that were from proteins of ubiquitous or tissue restricted expression. In vivo, these endogenous self peptides are not naturally presented in sufficient density by somatic cells expressing MHC class I molecules. They can, however, be presented if added exogenously. Thus, our data imply that CTLs are only tolerant of those endogenous self peptide sequences that are presented by MHC class I-positive cells in a physiological manner. PMID- 2321020 TI - Endogenous cholecystokinin reduces feeding in young rats. AB - The hypothesis that endogenous cholecystokinin (CCK) released from the small intestine during feeding causes satiety was tested in rat pups, 9 to 12 days old. Intragastric administration of soybean trypsin inhibitor, a procedure that releases CCK from the small intestine, decreased the subsequent intake of a test meal. This effect was reversed by prior treatment with MK-329, a selective antagonist of CCK at alimentary-type CCK (CCK-A) receptors. Thus, endogenous, small intestinal CCK can cause satiety in the neonatal rat and this effect involves CCK-A receptors. PMID- 2321021 TI - Genetic and physical mapping of the human genome. AB - In the table shown in the Briefing "Who leads the (Ivy) League in " 'citation impact'? " (9 Mar., p. 1183), the figures shown in the columns for "Citations" and "Citation impact" for Cornell University were incorrect. They should have been "523,878" and "16.53," respectively. The ranking was correct." PMID- 2321022 TI - Eastern Europe: missing an opportunity. PMID- 2321024 TI - Will protests derail AIDS meeting? PMID- 2321023 TI - British radiation study throws experts into tizzy. PMID- 2321025 TI - Making light work of cell surgery. PMID- 2321026 TI - Diffuse-double layer at a membrane-aqueous interface measured with x-ray standing waves. AB - The ion distribution in an electrolyte solution in contact with a charged polymerized phospholipid membrane was directly measured with long-period x-ray standing waves. The 27-angstrom-thick lipid monolayer was supported on a tungsten/silicon mirror. X-ray standing waves were generated above the mirror surface by total external reflection of a 9.8-kiloelectron volt x-ray beam from a synchrotron undulator. The membrane surface, which contained negatively charged phosphate headgroups, was bathed in a dilute ZnCl2 solution. The concentration of Zn2+ in the condensed layer at the membrane surface and the Zn2+ distribution in the diffuse layer were measured as a function of headgroup charge. The Debye length of the diffuse layer varied between 3 and 58 angstroms. The results qualitatively agree with the Gouy-Chapman-Stern model. PMID- 2321027 TI - Two-photon laser scanning fluorescence microscopy. AB - Molecular excitation by the simultaneous absorption of two photons provides intrinsic three-dimensional resolution in laser scanning fluorescence microscopy. The excitation of fluorophores having single-photon absorption in the ultraviolet with a stream of strongly focused subpicosecond pulses of red laser light has made possible fluorescence images of living cells and other microscopic objects. The fluorescence emission increased quadratically with the excitation intensity so that fluorescence and photo-bleaching were confined to the vicinity of the focal plane as expected for cooperative two-photon excitation. This technique also provides unprecedented capabilities for three-dimensional, spatially resolved photochemistry, particularly photolytic release of caged effector molecules. PMID- 2321028 TI - The effect of electrical coupling on the frequency of model neuronal oscillators. AB - Neurons with oscillatory properties are a common feature of the nervous system, but little is known about how neural oscillators shape the behavior of neuronal networks or how network interactions influence the properties of neural oscillators. Mathematical models are used to examine the effect of electrically coupling an oscillatory neuron to a second neuron that is either silent or tonically firing. Models of oscillatory neurons with varying degrees of complexity show that this coupling can either increase or decrease the frequency of an oscillator, depending on its membrane potential wave form, the state of the neuron to which it is coupled, and the strength of the coupling. Thus, electrical coupling provides a flexible mechanism for modifying the behavior of an oscillatory neural network. PMID- 2321030 TI - Macintosh laboratory automation: three software packages. PMID- 2321029 TI - Society, cure thyself. PMID- 2321031 TI - Acute muscle injury complicating sickle cell crisis. PMID- 2321032 TI - NSAID gastropathy. PMID- 2321033 TI - A Vietnamese veteran with multiple pleural nodules. PMID- 2321034 TI - Carcinoma of the lung. PMID- 2321035 TI - Organ donation: a vital role. PMID- 2321036 TI - Adapting the lithotripsy experience for a three year old. PMID- 2321037 TI - Care of the renal transplant patient: surveillance and troubleshooting are the keys. PMID- 2321038 TI - The radiologic assessment of post-traumatic vertebral stability. AB - The stability of the vertebral column depends upon the integrity of the bones, ligaments, and joints. The vertebral column can be divided into three distinct anatomic zones: anterior, middle, and posterior. Disruption of any single zone does not produce instability. Disruption of two contiguous zones will, however, significantly decrease the load-carrying capability of the spine and result in instability. Five radiographic signs indicative of vertebral instability have been identified: (1) displacement implies injury to major ligamentous and articular structures; (2) a wide interlaminar space implies injury to the posterior ligamentous structures and the facet joints; (3) wide facet joints imply injury to the posterior ligamentous structures; (4) a disrupted posterior vertebral body line implies burst injury with disruption of anterior bony and posterior ligamentous structures; (5) a wide vertebral canal implies injury to the entire vertebra in the sagittal plane. Each of these signs indicates disruption of a major skeletal, ligamentous, or articular structure and the presence of only one is sufficient to establish a diagnosis of instability. These conclusions are based upon a study of 138 injuries observed in 125 patients. PMID- 2321039 TI - Magnetic resonance imaging in acute and chronic rotator cuff tears. AB - Magnetic resonance imaging has been assessed in patients with acute rotator cuff tears and normal radiographs (9 cases) and those with chronic tears and changes of cuff arthropathy (9 cases). All images were obtained using a low field strength system (FONAR 0.3 T). Particular attention was placed on the appearances of the tendon and the cuff muscles themselves. Six complete acute tears were clearly identified, but MRI failed to demonstrate two partial tears. Muscle bulk was preserved in all patients in this group. In contrast, all patients with cuff arthropathy had complete tears of the supraspinatus tendon with marked tendon retraction and associated muscle atrophy: these changes precluded primary surgical repair. MRI should be used to assess muscle atrophy preoperatively in those patients with acute tears. When plain radiographs demonstrate cuff arthropathy, the MRI appearances are predictable and primary repair is unlikely to be successful. Further imaging is therefore not indicated. PMID- 2321040 TI - Negative scintigraphy with positive magnetic resonance imaging in bone metastases. AB - We report three patients with known primary tumor in whom radionuclide skeletal imaging for metastatic disease was normal with or without clinical symptomatology referable to this area. Magnetic resonance imaging (MRI) of the spine demonstrated focal areas of abnormal signal intensity in the vertebral bodies of these patients. In all three patients, biopsy confirmed metastatic disease. All the patients received radiation or chemotherapy depending upon the etiology. These preliminary data suggest that MR imaging may be useful in evaluating patients with known primary tumor in whom clinical suspicion persists despite a negative radionuclide bone scan. PMID- 2321041 TI - Sacral cysts with exophytic components. A report of two cases. AB - Sacral cysts are rare lesions. Two cases are presented, an aneurysmal bone cyst and a simple cyst. Simple cysts have not previously been described in the sacrum. Both cysts were asymptomatic, had similar radiographic appearances, and displayed significant exophytic components. PMID- 2321043 TI - Case report 578: Pigmented villonodular synovitis of the shoulder. PMID- 2321044 TI - Case report 596: Parosteal osteoma of the acetabulum. PMID- 2321042 TI - Magnetic resonance imaging in the evaluation of sequelae after tibial plateau fractures. AB - Nine knees with persistent radiographic depression of the articular surface after tibial plateau fractures treated by traction and early knee motion were examined using magnetic resonance imaging (MRI). The MRI examinations demonstrated that the radiographic bone defects were filled up with different tissues, which we interpreted as cartilage, fibrous tissue and synovial plica. The type of tissue in the bone defect did not seem to affect the functional capabilities of the knee. However, a demonstrable thin cover of tissue, with the signal-intensity of cartilage, over the defect, seemed to be associated with an excellent functional result. PMID- 2321045 TI - Case report 598: Os centrale carpi. PMID- 2321046 TI - Case report 599: Secondary oxalosis complicating chronic renal failure (oxalate gout). PMID- 2321047 TI - Case report 600: Post-radiation dermatitis with radiation-induced squamous cell carcinoma (well differentiated) of right third finger. PMID- 2321048 TI - Case report 602: Spindle cell hemangioendothelioma (SCH) and enchondromatosis (a form of Maffucci syndrome) in a patient with acute myelocytic leukemia (AML). PMID- 2321049 TI - Detection of local recurrent disease in musculoskeletal tumors: magnetic resonance imaging versus computed tomography. AB - A 2 1/2-year prospective study of surgically treated malignant mesenchymal neoplasms showed magnetic resonance imaging (MRI) to be superior to computed tomography (CT) in sensitivity for local recurrent disease measuring less than 15 cm3. Larger masses were detected with similar sensitivity; specificity and predictive values did not differ. The presence of areas of high signal intensity on T2-weighted images proved to be a reliable criterion except in fibrous neoplasms. However, differentiation between non-hemorrhagic fluid collections, cross-sectioned veins or bowel contents and small tumor nodules cannot be made simply by signal intensity, but has to be based upon the evaluation of gross morphologic criteria. PMID- 2321050 TI - Assessment of osteoporotic spine deformity. A new method. AB - For the objective assessment of the severity and progression of osteoporotic deformities of the spine, a mathematical model has been developed which permits evaluation of a single set of radiographs of the spine without reference to absolute values of vertebral height. The model was based on measurements of anterior, central and posterior heights of the vertebrae Th4 to L5 of 50 subjects, aged 20 to 50 years, without a history or radiologic signs of osteoporosis or other metabolic bone disease and without traumatic deformities. The model follows a simple sinusoidal function which describes the general form of the spine, adapted to the individual's height and build. A spine fracture index (SFI) is produced and the method allows calculation of the total number of vertebral deforming events (VDE), manner. The method has been used prospectively in 178 spine radiographs of 109 subjects (60 healthy early postmenopausal women and 49 with osteoporosis). Sensitivity and specificity of SFI in identifying osteoporotic patients were 94 and 88% respectively. In all 109 persons, densitometry of the spine was performed by dual photon absorptiometry at the same time. In the osteoporotic patients the examination was repeated once or twice during fluoride therapy for osteoporosis. The SFI and the total score of VDE and VDS correlated significantly with lumbar bone mineral content (r = -0.38 P less than 0.001). The method offers the advantage of being objective, not dependent on projection errors, and adaptable to the shape of the individual spine. PMID- 2321051 TI - Computed tomographic assessment of vertebral bone mineral in childhood. AB - Quantitative computed tomography (QCT) was used to assess trabecular bone mineral concentration in the vertebrae of 132 children, 45 with suspected disorder of bone mineralisation, 54 with thalassaemia and 37 controls. The range for bone mineral concentration in controls, expressed as equivalent K2HPO4 concentrations, was 90-190 mg cm-3. Abnormally low values were seen in all untreated children with idiopathic juvenile osteoporosis, 3/9 steroid recipients, and three patients with osteogenesis imperfecta. Abnormally high values were seen in 10/14 chronic renal failure patients. Comparison of the single and dual-energy methods showed that the single energy method, which has a lower radiation dose and is less prone to error from movement artifact, is satisfactory in most paediatric applications. PMID- 2321052 TI - [Skin antiseptics]. PMID- 2321053 TI - [Making the unoccupied bed]. PMID- 2321054 TI - [Cardiovascular manifestations of hyperthyroidism]. PMID- 2321055 TI - [The thyroid gland and iodine overloading]. PMID- 2321056 TI - [Pain medications]. PMID- 2321057 TI - [Tumor markers]. PMID- 2321058 TI - [Breast cancer screening]. PMID- 2321059 TI - [The nursing conflict. Organizational conflict or psychological conflict]. PMID- 2321060 TI - [Specific nursing diagnoses and nursing care plans. A memory chart]. PMID- 2321061 TI - [A nursing school librarian]. PMID- 2321062 TI - [Legal disciplinary actions of nurses and personnel in public hospitals]. PMID- 2321063 TI - Ciguatera fish poisoning: barracuda's revenge. PMID- 2321064 TI - Early glottic carcinoma. PMID- 2321065 TI - Early glottic carcinoma: patterns and predictors of relapse after definitive radiotherapy. AB - Although definitive radiotherapy in the management of early glottic carcinomas continues to offer excellent control, a small proportion of patients will have relapse. Between January 1972 and December 1984, 148 patients with squamous cell carcinoma of the glottis (stage I in 95 patients and stage II in 53 patients) had definitive radiotherapy at the University of Virginia Medical Center. We retrospectively analyzed patient data in an attempt to identify patients at risk for relapse and the patterns of failure. The three-year determinate survival for the entire population was 94.5% (stage I--100%, stage II--86%). Twenty of the 148 patients (14%) had relapse after radiotherapy. Failure in the primary site alone was observed in 17 patients (11%), two patients (1%) had relapse in the lymphatics of the neck without evidence of primary recurrence, and one patient (0.7%) had both neck and distant disease. Of the 19 patients who had definitive surgery after recurrence, 13 (68%) were successfully salvaged. Multivariate analysis was done to identify independent factors on relapse and survival. Statistically significant factors included persistent hoarseness after radiotherapy (P = .00005), impaired cord mobility (P = .00002), subglottic extension (P = .02), anterior commissure extension (P = .001), and multifocal involvement in stage I disease (P = .0008). We conclude that a majority of the small patient population with recurrent glottic carcinoma after radiotherapy may be salvaged with surgery, and we have identified patients at increased risk for recurrence. PMID- 2321066 TI - Ciguatera fish poisoning: an outbreak associated with fish caught from North Carolina coastal waters. AB - Ten persons who had eaten at a seafood meal in North Carolina had gastrointestinal and neurologic symptoms suggestive of ciguatera fish poisoning. In five persons, the neurologic morbidity lasted 30 days or longer. The meal included barracuda, dolphin fish (mahimahi), and yellow-fin tuna, all of which were caught in North Carolina coastal waters. Analysis of food-specific attack rates implicated the barracuda as the probable cause of the outbreak. We believe this is the first suspected or confirmed report of ciguatera fish poisoning associated with consumption of fish harvested from mainland US coastal waters outside of Florida. Physicians treating patients with a syndrome resembling ciguatera fish poisoning should inquire about consumption of fish not only from areas where the disease is endemic but also from the southeastern US. PMID- 2321067 TI - Obstructive sleep apnea syndrome: correction by mandibular advancement. AB - The obstructive sleep apnea syndrome (OSAS) is being recognized with increasing frequency in patients whose loud "heroic" snoring is coupled with significant and frequently debilitating daytime somnolence. Polysomnographic testing can clearly establish the diagnosis of this problem, but the etiology is multifactorial and the treatment options are varied. Although mandibular retrusion is not infrequently identified in patients with OSAS, the role of mandibular advancement surgery in the treatment of OSAS has not been defined. A nonobese 43-year-old white man with documented OSAS and mandibular retrusion had multidisciplinary treatment including surgical advancement of the mandible in conjunction with orthodontic treatment and prosthetic dental rehabilitation. No operation was done on the palate, nor was any other treatment provided for the OSAS. Resolution of the OSAS with dramatic improvement of the patient's snoring was achieved. This case illustrates the successful integration of corrective jaw surgery into the treatment plan for this type of patient. PMID- 2321069 TI - Clindamycin/primaquine therapy and secondary prophylaxis against Pneumocystis carinii pneumonia in patients with AIDS. AB - We found a program of intravenous and subsequent oral clindamycin, combined with oral primaquine, to be effective for Pneumocystis carinii pneumonia in nine patients with AIDS. The pneumonias were either primary or recurrent and sometimes severe, with cavity formation and/or pneumothorax. Maintenance therapy at lowered dose by mouth was effective in preventing recurrence in seven patients. One patient died of other opportunistic infections on day 24, and therapy was discontinued in another on day 11 because of skin rash. We conclude that clindamycin/primaquine is effective for therapy of P carinii pneumonia in patients with AIDS, as well as for long-term secondary prophylaxis at lowered dosage. PMID- 2321068 TI - Cardiovascular screening in Army personnel over age 40 in the State of Hawaii. AB - A cardiovascular screening protocol was applied prospectively to 1,900 soldiers over 40 years of age to identify individuals with latent coronary artery disease. Primary screening included a cardiovascular history, physical examination, electrocardiogram, serum cholesterol and serum glucose determinations, and calculated Framingham risk index. Seven hundred ninety-six individuals required secondary screening, consisting of stress testing and cardiac fluoroscopy. The screening process led to coronary angiography in 43 individuals; of these, 17 had obstructive coronary artery disease, ten had nonobstructive coronary artery disease, and 16 had normal coronary arteries. Application of primary screening before exercise testing increased the posttest probability of obstructive coronary artery disease to 50% in the individuals with a positive treadmill test. This is four times the expected value of 11% calculated using Bayes' theorem. The combination of a positive treadmill test and the finding of coronary artery calcification on fluoroscopy was an excellent predictor of obstructive coronary artery disease. PMID- 2321070 TI - Long-term follow-up after leptospirosis. AB - Human leptospirosis is an infectious disease that is a substantial problem in the Third World, but it can occur in developed countries as well. Survivors of the acute disease are considered to recover without sequelae, though little literature exists on long-term follow-up among these patients. Eleven patients, at an average of 22 years after acute leptospirosis, were reevaluated for possible delayed sequelae. Results showed that liver and renal disease had resolved, but headache and ophthalmic sequelae persisted. Even though the number of patients involved in this study is small, it appears that the eyes, particularly the anterior chambers, may be the site of continuing morbidity after acute human leptospirosis. The pathogenesis for persistent headache is not known. PMID- 2321071 TI - Computerized tomography in the evaluation of myasthenia gravis. AB - Thymomas occur in 10% to 15% of patients with myasthenia gravis. Since not all patients are referred for thymectomy, a test that could reliably predict the presence or absence of a thymoma would be of great assistance in the management of these patients. We studied all patients referred for thymectomy at Walter Reed Army Medical Center from 1983 to 1989. Complete records were available for 13 patients. Computerized tomography (CT) correctly predicted the presence of a thymoma in one patient and falsely predicted a thymoma in a patient with a thymic cyst; it accurately predicted the absence of a thymoma in the remaining 11 patients. The sensitivity of CT scanning was 100%, the specificity was 92%, and the accuracy was 92%, results that are in agreement with previously published data. Compared to conventional chest roentgenography, CT scanning provided a more precise anatomic localization, and accurately predicted local invasion. We recommend a CT scan of the mediastinum in all patients with myasthenia gravis to avoid delayed diagnosis of thymoma in patients who normally would not be referred for thymectomy. PMID- 2321072 TI - How physicians deal with their own impending death. PMID- 2321073 TI - Acute abdominal conditions in mesenteric lymphangioma. AB - Mesenteric lymphangiomas are rare benign tumors that occur in the abdominal cavity attached to the mesentery of the small or large bowel. They are no longer believed to be neoplasms, but may be a result of congenital failure of the original lymphaticovenous system. I have reported four cases of mesenteric lymphangioma causing an acute abdominal condition. Segmental resection of the intestine and the cystic mass was done in all patients, and all recovered uneventfully. There were no postoperative complications or recurrences. PMID- 2321074 TI - Disseminated cutaneous and synovial Mycobacterium marinum infection in a patient with systemic lupus erythematosus. AB - A patient with systemic lupus erythematosus had a protracted skin infection with Mycobacterium marinum after a puffer fish sting. Disseminated cutaneous and synovial disease was associated with clinically active systemic lupus erythematosus two years after the initial infection. The infection was poorly responsive to multiple antituberculous regimens. Hematogenous spread of infection was the likely route of dissemination. PMID- 2321076 TI - Antiarrhythmic properties of amitriptyline. AB - Clinical studies and case reports have shown that nortriptyline and imipramine exert type 1 antiarrhythmic properties when plasma concentrations are therapeutic, indicating that clinical reservation against their use in cardiac patients may be overstated. The clinical cardiac effects of amitriptyline have not been extensively reported. The case I have reported details the electrophysiologic record of the beneficial and safe use of amitriptyline in a patient with severe cardiac arrhythmias and organic affective disorder. PMID- 2321075 TI - Recurrent aphthous stomatitis and vitamin B12 deficiency. PMID- 2321077 TI - Pentamidine-induced torsades de pointes in a renal transplant recipient with Pneumocystis carinii pneumonia. AB - Pentamidine isethionate, an important agent used to treat Pneumocystis carinii pneumonia, has been shown to be associated with the development of torsades de pointes in patients with AIDS. We have described a case of pentamidine-induced polymorphous ventricular tachycardia in a renal transplant recipient whose renal insufficiency may have prolonged the duration of arrhythmias. Careful ECG monitoring should be done during pentamidine administration, especially in patients with renal insufficiency. Physicians should be aware that this variety of polymorphous ventricular tachycardia can occur well within the recommended dose of pentamidine. More data are needed to define the relationship between renal dysfunction, plasma levels, and pentamidine cardiotoxicity. PMID- 2321079 TI - Subcutaneous port or what is in a name? PMID- 2321078 TI - Survival of patients with sickle cell anemia living at high altitude. PMID- 2321080 TI - The changing face of radiation oncology. PMID- 2321081 TI - [Analysis of the planning of emergency medical services]. AB - The paper analyses the methods of planning the resources for emergency medical care. The precise method for the determination of resources providing the target probability of urgent medical care is suggested. A corresponding programme for microcalculator has been worked out and a graphic method of calculation has been given. PMID- 2321083 TI - [Current views of physicians with regard to traditional moral values]. PMID- 2321082 TI - [Organization of the activities of an outpatient department of a regional pulmonologic center]. AB - Ten years of experience in the work of specialized pulmonary centre providing care for the population of the region has indicated that during this period it has had a major impact on health care delivery and quality of care for the pulmonary patients. There has been improvement in early diagnosis and outcomes of treatment in patients with pulmonary diseases. The primary invalidism associated with chronic non-specific lung diseases has tended to decrease. PMID- 2321084 TI - [The main trends in the journal "Sovetskoe zdravookhranenie" in 1990]. PMID- 2321085 TI - [Socio-hygienic characteristics of primiparae over 30 years of age]. AB - A complex sociohygienic study of primaparous women aged 30 and over enables one to believe that along with leading biological risk factor, that is age, sociohygienic and medicodemographic factors also play an important role. This group of primaparous women requires special attention on the part of obstetricians and other specialists. One of the priorities are health-promoting activities before and during pregnancy and also the expansion of specialized medical care provided to them. It is suggested to develop a special prevention programme for this group of primaparas, distribute special information booklets, conduct interviews and group studies on the subject. PMID- 2321086 TI - [Problem of the prevalence of congenital malformations]. AB - Birth-histories and files of 42,275 newborn infants, ambulatory outpatient files of 38,280 children aged between 6 days and 15 years, and also findings of 4,153 autopsies were studied. The study was conducted for the years 1979-87. It was found that on the whole the incidence of congenital malformations (CM) in children 0-15 years old was 2.83 percent, last three years this indicator being 3.27 percent. Among stillborns the proportion of CM was 10.2 percent, among newborns--13.8 per 1,000 and for the last three years it rose up to 18.2. The leading congenital defects in newborn infants, according to prevalence, were malformations of organs of movement, abdominal wall and gastrointestinal tract, malformations of cardiovascular system. The analysis of CM structure among dead children indicated that the most prevalent were malformations of the central nervous system and also two last above-mentioned groups. The majority of children with CM among the dead were children of the first year of life. Proceeding from these findings the principal ways of CM prevention were suggested and main risk groups with regard to birth defects were identified. PMID- 2321087 TI - [Characteristics of the development of attitudes to health among female industrial and agricultural workers]. AB - Both the occupational and social factors play an equally important role in the formation of the attitude to health among working women. The study of public opinion is an important link in the solution of problems pertaining to the improvement of health care delivery to the working women. PMID- 2321088 TI - [Medico-hygienic standards of a healthy life style]. AB - Under conditions of rise in the incidence of chronic noncommunicable diseases increasing attention is being paid by science and public to the personal responsibility of man for his own health, an emphasis is being placed on the priority of healthy lifestyle formation. Different approaches to the definition of the concept and contents of healthy lifestyle hampers the organization and lowers the effectiveness of hygienic education of the population. The author suggests nine priority behavioral medico-hygienic norms which should form the basis for healthy lifestyle formation. PMID- 2321089 TI - [Experience with the ambulatory rehabilitation treatment of patients after myocardial infarction]. PMID- 2321090 TI - [Problem of physical development and health status of schoolchildren]. AB - Dynamic observation of schoolers' physical development and health status was carried out during 1973-1983. The study indicated decrease in acceleration rates and changes in morbidity trends. The correlation between health status and physical development and somatotype was demonstrated. When assessing the impact of ecologic situation on population's health it was necessary to take into account child group morbidity, physical development and health status. PMID- 2321091 TI - [Current problems in the planning of public health institutions]. PMID- 2321092 TI - [The role of the institutes and schools of post-graduate training in the certification of physicians and pharmacists]. PMID- 2321093 TI - [Regarding the article by F.G. Grigor'ev "Improving annual statistical records" (Sovetskoe zdravookhranenie 1989 No. 2, pp. 31-36)]. PMID- 2321094 TI - GC-rich murine adenosine deaminase gene promoter supports diverse tissue-specific gene expression. AB - The murine adenosine deaminase (ADA) gene has a GC-rich promoter that is structurally typical of many mammalian "housekeeping" gene promoters. The ability of the ADA gene promoter to support diverse tissue-specific gene expression was investigated. Endogenous ADA gene expression in different mouse tissues was found to vary over a greater than 3000-fold range in a highly complex pattern. This range of expression was also observed in cultured human cell lines derived from different tissues. The ADA levels in all tissues and cell lines examined correlated closely with steady-state ADA mRNA levels. Several of the mouse tissues examined also showed stage-specific variation during postnatal development. In order to determine whether tissue-specific ADA expression was controlled by cis-acting sequences upstream of the coding region, constructs containing a reporter gene regulated by the ADA gene's 5' flanking sequences were used to generate transgenic mice. All transgene-expressing mice obtained showed diverse reporter gene expression in the tissues analyzed. Our results demonstrate that both in vivo and in the context of an integrated transgene this GC-rich promoter can support highly diverse gene expression in all tissues of the animal. PMID- 2321095 TI - Characterization and localization to human chromosome 1 of human fast-twitch skeletal muscle calsequestrin gene. AB - A genomic clone encoding human fast-twitch skeletal muscle calsequestrin was isolated, and the amino acid sequence of the protein and the exon-intron boundaries of the gene were deduced from its sequence. A comparison with the rabbit gene showed that the sequence Glu-Asp-Asp-Asp-Asp near the COOH terminus of the rabbit sequence is lacking in the human gene. The calsequestrin gene was assigned to human chromosome 1 through the use of a human-mouse somatic cell hybrid mapping panel. PMID- 2321096 TI - Absence of uvomorulin in a slowly compacting variant of H6 embryonal carcinoma cells. AB - When allowed to aggregate in calcium-containing medium, the H6 embryonal carcinoma cell variant named 6B(NG)C25 compacted more slowly than wild-type cells, and aggregates of hybrids between it and wild-type cells also compacted slowly, as if the variation (mutation) acted in a dominant fashion. In agreement with this, we now have found that the cell adhesion molecule uvomorulin is markedly reduced or absent in 6B(NG)C25 cells, as well as in the hybrids. A small amount of a higher-molecular-weight protein reacting with the antibody is present, which might represent residual uvomorulin migrating at a slower rate, an altered uvomorulin, the known precursor to uvomorulin, or an unrelated cross reacting protein. PMID- 2321097 TI - [Angiographic demonstration of the branching of the popliteal artery in the arteries of the lower extremity--variations and frequency distribution]. PMID- 2321098 TI - [Changes in the concentration of plasma histamine and the blood electrolyte picture following the venous administration of nonionic x-ray contrast media]. PMID- 2321099 TI - [The significance of different soft tissue density values for the differential diagnosis of mediastinal space-occupying lesions in CT]. PMID- 2321100 TI - [Computed tomographic signs of peritoneal carcinosis]. PMID- 2321101 TI - The case for HIV surveillance in South Africa. PMID- 2321102 TI - 'Birth to Ten'--a study of children of the 1990s living in the Johannesburg Soweto area. PMID- 2321103 TI - Short-term predictions of the prevalence of human immunodeficiency virus infection among the black population in South Africa. AB - After a brief methodological review of acquired immunodeficiency syndrome/human immunodeficiency virus (AIDS/HIV) forecasting methods, some of these methods were applied to the South African situation and short-term predictions of the prevalence of HIV infection among the black population in South Africa were obtained. At present, the prevalence of HIV infection increases exponentially, with a doubling time of 8,5 months (95% confidence interval 7,6-9,6 months). By the end of 1989 the number of HIV-infected black South Africans aged 15-49 years was estimated to be between 45,000 and 63,000, and it is predicted that these numbers will rise to between 119,000 and 168,000 by the end of 1990, and to between 317,000 and 446,000 by the end of 1991. Because of the lack of basic data, these forecasts are tentative, but they nevertheless indicate the great seriousness of the HIV epidemic in South Africa. PMID- 2321104 TI - Ascites and serum bilirubin value predict survival in acute variceal bleeding. AB - Factors affecting the outcome of acute variceal haemorrhage treated by injection sclerotherapy were analysed. The data on 82 patients undergoing their first admission for acute variceal bleeding were collected prospectively. Using multiple logistic regression analysis and multiway contingency table analysis only the presence of ascites and an elevated serum bilirubin value contributed independently to survival out of a total of 26 discontinuous and 12 continuous variables. A derived regression equation was constructed to predict survival using the data from the 82 patients and this was tested against the observed outcome in a different group of 113 patients also undergoing their first variceal haemorrhage treated by injection sclerotherapy, the data from whom were also collected prospectively. Using a cut-off point of P = 0,71, the equation accurately predicted death for 91% of patients who died and accurately predicted survival for 65% of patients who survived. Overall accuracy of prediction was 73%. PMID- 2321106 TI - Visual stool examination--a screening test for infants with prolonged neonatal cholestasis. AB - Visual inspection of stools for the presence or absence of bile pigment was evaluated prospectively to determine its value in differentiating between biliary atresia and hepatitis. In a group of 23 infants with prolonged neonatal cholestasis the presence of stool pigment excluded extrahepatic biliary atresia, while its absence was suggestive of extrahepatic biliary atresia. This simple test was found to be more reliable than more sophisticated diagnostic techniques. PMID- 2321105 TI - [Intravesical BCG as a treatment for superficial and in situ transitional cell carcinoma of the bladder]. AB - Intravesical BCG is already established as effective therapy in the management of superficial bladder cancer. However, varying results have been obtained with different BCG strains; these are ascribed to variations in their immunogenicity. The locally available BCG strain which contains approximately 1.2 x 10(9) colony forming units per 120 mg was used for intravesical instillation in 27 patients with recurrent superficial transitional cancer of the bladder. Ten of the 13 patients who received BCG prophylactically to reduce or stop recurrencies completed therapy and 7 (70%) were in remission after 1 or 2 courses with a mean follow-up of 2 years. Fourteen patients received BCG therapeutically for in situ carcinoma. Thirteen of these patients completed therapy and 9 (69%) responded favourably after 1 or 2 courses of BCG for a mean follow-up period of 23 months. Adverse effects of the treatment were mild and well tolerated except in a patient who received radiotherapy. Although 21 patients experienced irritable bladder symptoms only 1 discontinued treatment as a direct result. The only other patient in whom treatment had to be stopped, developed severe polyarthritis after 3 instillations. A statistically significant reduction in the number of recurrences (P less than 0.001) was experienced by the patients who received BCG prophylactically. Although this is a very limited study, the locally available BCG strain exhibited therapeutic activity. It is cost-effective and warrants further study. PMID- 2321107 TI - Motion sickness--vestibular habituation with the centrifuge. AB - People who are prone to motion sickness have a directional preponderance of nystagmus to the left. Centrifuging will change this preponderance to the right in most people, and at the same time reduce their tendency towards motion sickness but only with regard to air travel. PMID- 2321108 TI - Monitoring in motion. An update on the Air Ambulance Service of the South African Red Cross Society (Cape Region). AB - Since 1966, when 40 patients were transported in a single-engined light aircraft in its first year of service, the Air Ambulance Service of the Cape Region of the South African Red Cross Society has continued to grow annually, providing the people of southern Africa with a remarkable and, in its many ways, unique service. More than 3,300 patients have been transported on more than 2,500 flights in the past 23 years. In June 1988, a Cessna Citation jet aircraft was taken into service and, by 20 January 1989, had already transported more than 148 patients on 102 flights. This aircraft was equipped in Cape Town and has sophisticated life support and monitoring equipment, which enables critically ill patients to be transported over long distances in safety. PMID- 2321109 TI - Successful pregnancy despite retrograde ejaculation. A case report. AB - In retrograde ejaculation sperm is passed into the bladder causing infertility. Among patients seen at the Reproductive Biology Research Unit of the University of Pretoria retrograde ejaculation is relatively uncommon (0.004%), but is a potentially treatable cause of infertility. The technique for collecting sperm, sperm processing and recovery described was successful and resulted in a pregnancy after transfer of 1 four-cell embryo. PMID- 2321110 TI - Benign symmetrical lipomatosis--a complication of excessive alcohol consumption. A case report. AB - A case of benign symmetrical lipomatosis (Madelung-Launois-Bensaude syndrome) is described. The characteristic clinical features and the association with chronic alcoholism are reported. PMID- 2321111 TI - Cosmetic ochronosis caused by bleaching creams containing 2% hydroquinone. PMID- 2321112 TI - T-cell-rich B-cell lymphoma. PMID- 2321113 TI - Acute benign pulmonary histoplasmosis--the third known outbreak in the Cape Province. PMID- 2321114 TI - Management of variceal hemorrhage. PMID- 2321115 TI - Small-diameter portacaval H-graft for variceal hemorrhage. AB - This report describes the steps in the development of the concept of partial shunting from its earliest stages to the 8-mm-diameter portacaval H-graft. Sequentially decreasing the diameter of the graft from 20 mm did not seem to affect hepatic hemodynamics until the 10-mm-diameter graft was used. At this point, we began to see some patients maintain prograde portal flow. Further reduction in diameter gave a higher rate of patients with prograde flow. Postoperative flow patterns correlate with lower encephalopathy rates and better long-term survival. Important nuances of the operative technique as well as pre- and postoperative management are described. PMID- 2321116 TI - Fiberoptic endoscopy of the gastrointestinal tract in surgical training. AB - In 1981, the American Board of Surgery encouraged applicants for board certification to be familiar with a variety of endoscopic techniques upon the gastrointestinal tract. In 1983, the Department of General Surgery at Naval Hospital, San Diego established a surgical gastrointestinal endoscopy unit to train physicians to perform endoscopic procedures. Since its inception, more than two thousand procedures have been performed. The results of esophagogastroduodenoscopy and colonoscopy performed between January 1986 and October 1987 provide the numeric basis in our evaluation of our program for endoscopic training and support training in endoscopy as integral to the education of the resident in general surgery. PMID- 2321117 TI - The role of second-look procedure in improving survival time for patients with mesenteric venous thrombosis. AB - Since 1978, 21 patients (12 men and nine women) suffering from mesenteric venous thrombosis (MVT) were treated at the Hadassah University Medical Center. The cause of MVT was multifactorial, and in only six patients was the process defined as primary or idiopathic. A preoperative diagnosis of MVT was made in eight patients. Surgical management of the individual patient was based on the extent of the ischemic process, the viability of infarcted intestine and the general condition of the patient. Nineteen patients were operated upon. Exploratory laparotomy without any attempt of intestinal resection was performed upon two patients. Eleven patients underwent resection and primary anastomosis. Second look procedures were done upon ten patients, and in six, intestinal resection was followed by creation of a double ostomy. The over-all survival rate was reported to be 60 per cent; it was 71 per cent among the patients who were operated upon. The role of second-look procedures in improving survival time is outlined. PMID- 2321118 TI - Incidence of mortality in boys and girls after severe thermal burns. AB - One hundred and eighty-five children with burns, 118 boys and 67 girls, all of whom had thermal burns covering more than 30 per cent of the body surface area without complications from inhalation injury, were studied to determine whether boys or girls better survive massive skin burns and if a high mortality group within these populations could be identified. A significantly higher mortality rate (15 per cent) was noted for boys when compared with girls (3 per cent), with 44 per cent of the deaths in boys identified in the greater than 95th percentile body weight-for-age distribution. PMID- 2321119 TI - Vaginal hysterectomy without ligation of the ligaments of the cervix uteri. AB - An operative procedure for vaginal hysterectomy is reported. The procedure is performed without ligation of the paracervical ligaments to simplify and avoid ureteral injury. However, a portion of the cardinal ligament is ligated before peritoneal closure. In a study from 1955 to 1987, of 9,230 patients requiring vaginal hysterectomy, blood loss was less than 300 milliliters with this procedure in 83 per cent of the patients. Operative complications, such as bladder injury, occurred in 66 patients or 0.7 per cent. Ureteral injury occurred in only three patients or 0.03 per cent. From 1972 to 1987, only five of 2,460 patients (0.02 per cent) required postoperative hemostasis. These data indicate that vaginal hysterectomy without ligation of the paracervical ligaments is a safe and convenient operative method with fewer complications. PMID- 2321120 TI - Genital swelling as a surgical complication of continuous ambulatory peritoneal dialysis. AB - Genital edema was seen as a complication of continuous ambulatory peritoneal dialysis (CAPD) in 18 patients, who accounted for 4 per cent of all patients on CAPD. In the majority of patients, the swelling developed suddenly and painlessly in the scrotum, penis or labia majora. Some of the patients noticed ultrafiltration failure. In the majority of these patients, this was a result of fluid leakage through the patent processus vaginalis. In one female patient, fluid leaked through the implantation site of the catheter. A computed tomographic scan using contrast media is a useful diagnostic tool in identifying the side of the defect in patients with generalized scrotal or penile edema. Surgical repair of the hernia and the hole in the processus vaginalis or hernia sac prevented recurrence. A trial of temporary discontinuation of CAPD or intermittent peritoneal dialysis using small volumes of dialysis fluid prevented recurrence while reinstituting CAPD in patients with normal findings from contrast studies. Intermittent peritoneal dialysis using low volumes of dialysis fluid with stepwise increase prevented recurrence while reinstituting CAPD two to three weeks after surgical repair. PMID- 2321121 TI - Lymphoreticular disease masquerading as or associated with an inguinal or femoral hernia. AB - Twelve patients (eight men and four women) had previously undiagnosed lymphoreticular disease associated with or simulating an inguinal (nine) or femoral (three) hernia. The disease was present on the left side in eight. Four patients (three women and one man) did not have an actual hernia. Two of these women had a preoperative diagnosis of femoral hernia. Seven of the patients, including all of the women, had non-Hodgkin's lymphoma (three diffuse large cell, two follicular mixed cell and two follicular small cleaved cell) and one patient had lymphocytic predominance (nodular lymphocytic and histiocytic) Hodgkin's disease. No stage predominated. Inguinal lymph nodes from two patients showed, histologically, Kaposi's sarcoma and type I human immunodeficiency virus (HIV) associated disease. Each patient was homosexual and HIV seropositive. Changes suggestive of viral cause were present in the lymph node of one patient. The enlarged lymph nodes of the 12th patient showed stellate suppurative granulomas containing cat-scratch bacilli demonstrated by Warthin-Starry stain. Because of the special processing needs for lymphoreticular diseases and potential for misdiagnosis, surgeons, clinicians and pathologists should be aware of the spectrum of lymphoreticular processes occurring in lymph nodes associated with or masquerading as a hernia, particularly in women. PMID- 2321122 TI - Arterial reconstruction in patients with polycythemia vera. AB - The natural history of polycythemia vera (PV) with its inherent arterial and venous complications are well described but the results of arterial surgical treatment in patients with PV are not known. This study was done to determine the outcome of arterial surgical treatment in patients with PV. During the last six and one-half years, of 2,603 extensive vascular procedures performed, seven reconstructions were performed upon six patients with PV. Extensive complications occurred in 57 per cent of this group. All of the complications occurred in patients with disease of the lower extremity and resulted in extensive amputation in one-half of the patients. The average preoperative platelet count was higher (420,000) in patients with complications as compared with those who did well (303,000). All of the patients requiring chemotherapeutic control of the PV (hydroxyurea) had extensive complications. These results indicate that vascular operations in patients with PV carry a high complication rate. A platelet count of more than 330,000, more than 70 years of age, infrainguinal reconstruction and PV requiring hydroxyurea for control seem predictive of a poor outcome. Although this series is small, we believe that great caution should be exercised before attempting vascular reconstructions in patients with PV and the aforementioned risk factors. PMID- 2321123 TI - Analysis of surgical complications after 397 hepatic transplantations. AB - The results of 397 consecutive orthotopic hepatic transplantations in 333 recipients were reviewed. One or more surgical complications developed in 172 of 323 patients (55 per cent), excluding ten intraoperative deaths. The six month mortality rate among the patients with surgical complications (55 of 172; 32 per cent) was statistically higher than that among patients without such complications (16 of 151; 11 per cent) (p less than 0.001; chi-square, 58.36). Surgical complications included exploratory laparotomy for bleeding or infection in 74 (22 per cent), reconstruction of the bile duct for biliary obstruction or leakage in 55 (17 per cent), external biliary drainage for biliary leakage in four (1 per cent), tracheostomy in 80 (24 per cent), thoracotomy in 12 (4 per cent) and splenectomy in seven (2 per cent). The incidence of biliary obstruction (16 per cent mortality rate) and leakage (48 per cent mortality rate) was 18 per cent (34 of 193) and 2 per cent (four of 193) each after choledochocholedochostomy, which was 3 per cent (five of 187) and 9 per cent (17 of 187) each after choledochojejunostomy. Biliary obstruction (16 per cent mortality rate) was more common after choledochocholedochostomy (p less than 0.005; chi-square, 23.01), whereas the incidence of more serious biliary leakage (48 per cent mortality rate) was higher after choledochojejunostomy (p less than 0.005; chi-square, 8.97). It is concluded that orthotopic hepatic transplantation remains an unforgiving extensive surgical procedure, in which choledochocholedochostomy remains the first-choice reconstruction of the biliary tract because of its lower mortality. PMID- 2321124 TI - Emergent cerclage. AB - Emergent cerclage may be defined as that performed in the setting of advanced cervical dilation with bulging or "hourglass" membranes. During a five year period, 15 patients with bulging or hourglass membranes and marked cervical dilation in the second trimester were treated with emergent cerclage. Included were two triplet gestations. Complications were limited to intraoperative rupture of fetal membranes in two patients and chorioamnionitis either in the early postoperative period (two) or later in pregnancy (three). Pregnancy was prolonged for a sufficient time to deliver viable fetuses in 11 of 15 patients. Eleven of 13 neonates of a gestational age of 24 weeks or more survived. The lack of significant maternal morbidity combined with the results for the fetus-infant supports further efforts in this area. PMID- 2321125 TI - Clinical evaluation of the response to surgical treatment of Graves' disease. AB - Included in this study are 513 patients with Graves' disease who underwent thyroidectomy between 1970 and 1983. The patients were divided into three groups by dividing the period in which the surgical procedures were done. The weight of the remnant of the thyroid gland and the incidence of surgical complications were collated for the patients in each group studied. Postoperative function of the thyroid gland was evaluated clinically and biochemically and compared with the remnant weight and total weight of the thyroid gland. The remnant weight was greatest in the first period and least in the third period. There were no differences between the frequencies of postoperative complications among the three groups in site of a remarkable decrease of the remnant weight in the third period. Remission of hyperthyroidism, including those with a latent hypothyroid state, was most frequently observed in the group in which the remnant weight was from 4 to less than 8 grams. These results indicate that the remnant weight appears to be one of the most crucial factors influencing the postoperative outcome; it thus seems appropriate to leave only small remnants of the thyroid gland (4 to less than 8 grams) at thyroidectomy. In our hands, surgical treatment is an effective and safe procedure for Graves' disease, although the precise mechanism for the remission induced by this procedure has not been elucidated. PMID- 2321127 TI - A technique for the performance of a safe pyloromyotomy. PMID- 2321128 TI - Augmentation of the bladder in preparation for renal transplantation. AB - Although loop urinary diversion has been used successfully with renal allograft recipients, the potential and real morbidity of these diversions has led us to avoid this type of reconstruction in favor of the reconstructed bladder (3). Many of our first patients had undergone reconstruction or undiversion prior to the establishment of renal insufficiency and had a variety of augmentations (two ileocecal and three sigmoid). One additional patient underwent ileal patch augmentation three years after transplantation. However, many patients are now being seen in preparation for renal transplantation who have urinary diversions or require reconstruction and have such poor renal reserve that renal replacement therapy is inevitable. It is this latter group of patients who have prompted us to define what is the most suitable form of reconstruction of the bladder when subsequent transplantation is planned. Many forms of reconstruction and undiversion are available and appear to be equally satisfactory in the management of patients with lower urinary tract dysfunction. However, patients who are to undergo renal transplantation subsequently should be given consideration regarding the technical feasibility of the transplant operation. Accordingly, we believe that simple augmentation of the sigmoid colon as described herein prevents dissection of either iliac fossa, which greatly facilitates implantation of the allograft. As there currently appears to be no superior segment of both the large and small intestine or configuration for augmentation, augmentation of the sigmoid colon is at least as effective as other modes of reconstruction and, therefore, should be strongly considered in this population of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321126 TI - Early and long term effects of a model of intestinal autotransplantation on intestinal motor patterns. AB - The short and long term effects of a model of orthotopic jejunoileal autotransplantation on intestinal motility were studied in a model of four dogs that underwent autotransplantation of the entire jejunoileum. Serosal electrodes were placed to record intestinal motility patterns. Each dog was studied during fasting and after feeding early (two to six weeks) and late (14 to 17 weeks) after jejunoileal autotransplantation. During fasting, both the innervated duodenum and the autotransplanted jejunoileum showed the characteristic migrating motor complex (MMC) early after this model of transplantation, but the MMC in the two regions lacked temporal coordination. Late after transplantation, temporal reassociation of the MMC in the duodenum and jejunoileum occurred. Feeding a small meal (50 grams of liver) inhibited the MMC in the duodenum, but not in the jejunoileum either early or late after transplantation. These observations suggest that characteristic cyclic fasting motility patterns persist after this model of small intestinal transplantation and are dissociated temporally between innervated and transplanted regions for at least eight weeks, but then reassociate with time (greater than three months). Feeding a small meal did not induce a postprandial motor pattern in the transplanted region. The effects of these changes in motility on intestinal function remain unknown. PMID- 2321129 TI - Isolated torsion of the normal fallopian tube in premenarchial girls. AB - Torsion of the normal fallopian tube in premenarchial girls is a very rare clinical entity with only four reported instances in literature. The clinical presentation of this entity is indistinguishable from acute appendicitis, and correct preoperative diagnosis is never made. The cause of torsion of normal fallopian tubes remains unknown. The surgical procedure of choice is salpingectomy, with care being taken to isolate and occlude the vascular pedicle prior to detorsion. PMID- 2321130 TI - A simplified technique for splenopancreatic disconnection with distal splenorenal shunt. PMID- 2321131 TI - Use of new transhepatic biliary stent tube in the treatment of biliary disease. PMID- 2321132 TI - Roentgenographic marking using surgical staples after in situ saphenous venous bypass. AB - A method to localize A-V fistulas is described herein, using sterile staples as makers with angiography. This may decrease the operative time spent searching for A-V fistulas and may diminish morbidity and help improve the patency of the graft. PMID- 2321133 TI - Major retroperitoneal venous anomalies: surgical considerations. AB - Nineteen major anomalies of the vena cava or its branches were encountered in patients requiring abdominal vascular surgery and related procedures at Barnes Hospital during the past 5 years. The classification of these anomalies, their embryologic development, associated variants, and surgical considerations are discussed. Careful review of preoperative computed tomographic scans and familiarity with these anatomic variants may allow the surgeon effectively to avoid potentially disastrous intraoperative consequences. PMID- 2321134 TI - Acute mesenteric ischemia: improved results--a retrospective analysis of ninety two patients. AB - Acute mesenteric ischemia (AMI) is a curable disease if diagnosis and therapy are instituted before irreversible changes have occurred. AMI has been diagnosed with increasing frequency, during the last two decades, yet the mortality rate remains as high as 80% to 95%. Ninety-two patients with AMI were treated at Hadassah University Hospital between 1952 and 1987. Seventy-seven patients were treated surgically: 15 underwent only explorative laparotomy, and 62 underwent bowel resection or revascularization or both. The latter patients were divided into two groups: 17 patients treated surgically between 1952 and 1976, in whom bowel resection and primary anastomosis was the only surgical procedure carried out (group 1), and 45 patients treated in the last decade (group 2), in whom one or more of the following procedures were performed: bowel resection with primary anastomosis (n = 16), revascularization (n = 16), "second-look" (n = 18), and delayed anastomosis (n = 10). The overall mortality rate in 62 surgically treated patients was 40% (82% in group 1 and 24% in group 2) and 21% in 29 patients treated in a combined surgical approach. The reasons for improved results in group 2 patients are discussed, and an algorithm for surgical treatment of patients with AMI of different causes is proposed. PMID- 2321135 TI - Aminoterminal propeptide of type III procollagen in serum during wound healing in human beings. AB - The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum as an indicator of tissue repair was studied in 71 surgical patients undergoing minor, moderate abdominal, major abdominal, or hip surgery. An increase in serum PIIINP concentrations took place within the first week, and its magnitude was related to the extent of the soft-tissue operations. After the hip replacement, the maximum PIIINP concentration was reached somewhat later. Very high levels of serum PIIINP were seen in three patients with serious wound infections. The serum PIIINP antigenicity consisted both before and after surgery of equal proportions of two forms, one corresponding to the propeptide as set free during synthesis of new collagen and the other being larger and probably derived from turnover of type III collagen fibers. The proportion of the latter form was accentuated in infection. In contrast, in the wound the form derived from synthesis of type III collagen predominated. These results suggest that the postoperative increase in serum PIIINP levels is partly the result of tissue repair and partly the result of whole-body turnover of type III collagen. PMID- 2321136 TI - Saphenous vein rupture pressure, rupture stress, and carotid endarterectomy vein patch reconstruction. AB - Early postoperative patch rupture is a catastrophic complication of carotid endarterectomy reconstruction with greater saphenous vein. Mechanical determinants of saphenous vein rupture were identified by structural measurements and the results applied to carotid endarterectomy patch geometry. Diameter and rupture pressure was measured in fresh saphenous vein segments from the ankle, knee, or thigh in 157 patients undergoing bypass operations. Circumferential hoop rupture stress was calculated and the results were applied to 157 carotid endarterectomy reconstructions. All vein ruptures were in the cylindric axis. The mean vein diameter was 4.58 mm. The mean vein rupture pressure was 2873 mm Hg (3.78 atm). Vein diameter was larger in the thigh than in the ankle or knee (p less than 0.01), but there was no significant difference in rupture pressure between veins from the three locations. Women had a smaller vein diameter than had men at all locations (p less than 0.01). There was a positive linear correlation between vein diameter and rupture pressure. The mean maximum diameter of curvature of 157 carotid endarterectomy reconstructions with a vein patch was 13.3 mm. Multiple random applications of the 157 veins to 157 carotid diameters predicted a mean patch rupture pressure of 1087 mm Hg (1.43 atm), 1163 mm Hg (1.53 atm) for men, and 866 mm Hg (1.14 atm) for women. Predicted vein patch rupture pressures less than 300 mm Hg were found in 5.7% of cases (8.8% women and 1.2% men). Only 0.6% of patients (1.8% women and 0% men) had a predicted rupture pressure less than 200 mm Hg. No veins with a diameter greater than or equal to 4.0 mm had a predicted patch rupture pressure less than 300 mm Hg. These results suggest that small-diameter saphenous veins have a higher risk of rupture when used as a carotid patch. PMID- 2321137 TI - Histologic and ultrastructural changes in nonpulmonary organs during early hyperdynamic sepsis. AB - Previous studies describing the histologic elements of multi-system organ failure caused by bacterial sepsis may have been complicated by a significant interaction on tissue injury from either a preterminal low-flow state or the effects of therapy immediately before death. Therefore we evaluated the nonpulmonary histologic findings of sepsis during a 3-day period that followed cecal ligation and perforation. In this septic model, mean arterial perfusion pressures remained unchanged from baseline, systemic flows rose by 54%, and laboratory evidence of organ dysfunction including an elevation of the serum bilirubin levels and a depression of the serum total protein values was considered mild. Concurrently, development of the hyperdynamic central circulatory septic state was associated with widespread histologic changes in myocardium, striated muscle, liver, gut, and pancreas. Lesions common to these organs included high-protein interstitial and intracellular edema, mitochondrial destruction, and patchy cell necrosis. Lesions within the pancreas were exaggerated over those noted in other organs. Of all organs examined, only the liver demonstrated microvascular neutrophil accumulation. Unlike models of shock caused by sepsis, fibrin thrombi were not seen in the microvasculature of any organ. We conclude that tissue injury characterized by the accumulation of protein-rich extravascular fluid and the development of reversible and irreversible cell injury antedated significant multiple-system organ failure in this animal model of normotensive sepsis. PMID- 2321138 TI - Additive interactions of calcitonin gene-related peptide and calcitonin on pancreatic exocrine function in conscious dogs. AB - By convention, establishing a physiologic role for a gut peptide requires demonstration of biologic activity that can be reproduced by exogenous administration of the peptide in amounts that yield plasma concentrations that are not higher than those found after a meal. We have tested the hypothesis that the combined action of two inhibitory peptides may lower the effective doses of each. We further hypothesize that combined peptide responses may be responsible for the action of peptide hormones that have been difficult to demonstrate as physiologically relevant mediators, when examined as independently acting substances. In conscious dogs prepared with chronic pancreatic cannulas, stimulated pancreatic exocrine secretions were depressed in a dose-related manner by intravenous infusions of calcitonin (CT) and calcitonin gene-related peptide (CGRP). Doses of 2.0 nmol/kg/hr of both CT and CGRP yielded maximal inhibition of stimulated secretions of both bicarbonate (greater than 85% inhibition) and protein (greater than 55% inhibition). The lowest effective dose for either CT or CGRP, given alone, was 0.75 nmol/kg/hr, but when infused simultaneously, each at the subthreshold dose of 0.50 nmol/kg/hr, significant inhibition of protein and bicarbonate secretion was achieved. Combined infusions of the submaximal dose of 0.75 nmol/kg/hr resulted in an enhanced inhibitory response. To prove that this effect is not simply combined activation of a common receptor, we tested peptide YY (0.1 to 0.5 nmol/kg/hr) combined with CGRP and obtained similar results. Because a meal simultaneously releases a large number of active peptides, we speculate that such potentiated responses do occur physiologically. Cooperative interaction with other agents may be the primary mode of action for certain gut peptides. PMID- 2321139 TI - Induction of an immune response to keyhole-limpet hemocyanin in surgical patients with anergy. AB - Groups of surgical patients, classified as reactive or anergic on the basis of delayed type hypersensitivity skin testing with five recall antigens, were immunized with keyhole-limpet hemocyanin (KLH) alone or KLH together with mediators derived from leukocytes of a KLH immune donor cultured with antigen. Patients with anergy injected with KLH alone did not generate an immune response as judged by a T cell proliferative reaction performed 14 days after immunization. In contrast, leukocytes of patients with anergy immunized with KLH together with the mediators reacted to KLH in vitro in similar numbers and with a magnitude comparable to that given by reactive, hospitalized patients without anergy immunized with KLH alone. These results confirm and extend our previous observations showing that anergy defined as a lack of cell-mediated immunity to recall antigens such as purified protein derivative extends to the generation of a systemic immune response to a neoantigen such as KLH and mediators that could restore a state of delayed hypersensitivity to purified protein derivative could also be instrumental in inducing cell-mediated immunity de novo when injected together with the antigen. PMID- 2321140 TI - Aneurysmal rupture of a femoropopliteal saphenous vein graft. AB - A case of a nonanastomotic, atheromatous aneurysm in a femoropopliteal saphenous vein graft is presented. This disease is unusual, especially in nonsmokers with normal lipid levels, and, in this case, may be related to mechanical graft failure 22 years after implantation. The aneurysm was excised and the arterial continuity reestablished with a prosthetic graft. PMID- 2321141 TI - Budd-Chiari syndrome: portacaval shunt and subsequent liver transplantation. AB - The Budd-Chiari syndrome (BCS) is caused by hepatic venous outflow obstruction, which often leads to death as a result of portal hypertension and liver failure. Therapeutic approaches vary widely from conventional medical therapy to liver transplantation. If and when a patient suffering with BCS needs surgery remains a matter of contention. However, it is well accepted that portacaval shunt surgery and orthotopic liver transplantation represent efficient surgical treatments of this condition. We report on a patient with an eventful course after BCS was diagnosed. After portacaval shunt surgery the patient had acute liver failure and had a successful orthotopic liver transplantation. PMID- 2321142 TI - Successful hepatic transplantation in congenital absence of recipient portal vein. AB - The first case of hepatic transplantation in a patient with congenital absence of the portal vein (CAPV) is reported. A 10-year-old girl with biliary atresia and CAPV underwent successful hepatic transplantation and has normal liver function 9 months after transplantation. This case is only the seventh reported case of CAPV. Patients with CAPV commonly have additional liver anomalies, cardiac and inferior vena cava anomalies, and polysplenia. Surprisingly, hepatic encephalopathy is not a prominent feature in patients with CAPV despite systemic drainage of mesenteric venous blood. CAPV should not be considered a contraindication to hepatic transplantation. PMID- 2321143 TI - Treating the modern assault rifle wound. PMID- 2321144 TI - [Methods in nursing. Affirmation is similar to positive brainwashing]. PMID- 2321145 TI - [Freedom from methods equal to free for methods?]. PMID- 2321146 TI - [Support group for those left behind]. PMID- 2321147 TI - [Nurses' income tax return]. PMID- 2321148 TI - [AIDS. Nurses on the job looked up rock stars]. PMID- 2321150 TI - [Something about models]. PMID- 2321149 TI - [Crisis leads to open Spanish health sector]. PMID- 2321151 TI - [Psychiatry. My sick daughter deserted by caregivers]. PMID- 2321153 TI - [Reality shock in Norwegian]. PMID- 2321152 TI - [What do we mean with quality of life?]. PMID- 2321154 TI - [Executive Board. Council for prevention should be based broadly]. PMID- 2321155 TI - [Uncertainty following new law on coercion in psychiatry]. PMID- 2321156 TI - [Patients should qualify for difficult choices]. PMID- 2321157 TI - [Everybody's input while hospital is renovated]. PMID- 2321158 TI - Nitrous oxide alters body laterality in rats. AB - Seventy timed-pregnant Sprague-Dawley rats were exposed to either air (control) or 75% nitrous oxide (N2O) for 24 hours on day 8 of gestation. Four rats from each group were killed on days 11-16, 18, and 20, and laparotomy was performed. The viability of the embryos/fetuses was determined, as was the side of tail flexion on days 11 and 12, the direction from which the umbilical artery emerged from the body on days 13 and 14, the side of the body facing the placenta on days 15 and 16, and the side to which the aortic arch curved on days 18 and 20. Mean mortality rate in the control group was 8.9 +/- 6.1% (+/- S.D.), and there were no control embryos/fetuses with altered laterality except the 9% that faced left on day 16. In contrast, N2O treatment on day 8 of gestation resulted in significantly increased mortality (40.8 +/- 3.3%) beginning on day 14 of gestation and increased incidence of altered laterality overall (31.3%) and at all stages of development. The mechanisms underlying these events remain to be defined, as do the implications of our findings for pregnant surgical patients and occupationally exposed workers. PMID- 2321159 TI - Role of maternal plasma corticosterone elevation in the teratogenicity of secalonic acid D in mice. AB - Secalonic acid D (SAD) is a teratogenic mycotoxin that causes cleft palate in the offspring of treated pregnant mice. To investigate the role of maternal corticosterone in the teratogenicity of SAD, pregnant CD-1 mice were treated with 30 mg/kg of SAD i.p. on day 11 of pregnancy in either 5% (w/v) NaHCO3 or 20% (v/v) dimethyl sulfoxide (DMSO) in NaHCO3. Radioimmunoassay (RIA) was performed to determine plasma corticosterone at 24, 48, 72, and 96 hr after dosing. No interference by EDTA, SAD, DMSO, or pentobarbital was noticed on the RIA. Significant (P less than .01) elevations in plasma corticosterone concentrations were seen 24 and 48 hr following dosing of SAD in NaHCO3 with concentrations reaching a peak just prior to the onset of shelf elevation and fusion. Simultaneous treatment with DMSO, an agent known to antagonize the teratogenic effect of SAD, completely abolished the SAD-induced corticosterone elevation at the 24 hr time point and significantly (P less than .01) reduced it at the 48 hr time point. To evaluate the specificity of the role of corticosterone in the teratogenicity of SAD, plasma samples from mature males similarly treated with either single or multiple doses of SAD ranging from 15 to 45 mg/kg were assayed for corticosterone. A dose of SAD comparable to that used in the pregnant females failed to significantly change plasma corticosterone concentrations in the males. An elevation corresponding only to 75% of that in the females was seen in males receiving multiple doses of SAD totaling three times the dose used in the females. As with females, DMSO completely abolished plasma corticosterone elevation by SAD in the males. These results demonstrate, for the first time, the effect of SAD on a mammalian endocrine system and provide evidence for a specific involvement of elevated maternal plasma corticosterone concentrations in SAD teratogenicity. PMID- 2321160 TI - Correlation between the birth prevalence of isolated hypospadias and parental subfertility. AB - Factors associated with the occurrence of isolated hypospadias have been studied. We previously reported a secular trend association between hypospadias occurrence and progestagen use by the Hungarian population. Further study does not support that secular trend association. The use of progestagens for the treatment of reproductive problems is a very complex issue, and there are other factors relating to male and female fertility that differentiate the hypospadias families from the controls. It appears that families with problems of subfertility are at increased risk for the occurrence of hypospadias. Our data support more recent studies, which do not demonstrate an association between the occurrence of hypospadias and the administration of progestagens in humans. PMID- 2321161 TI - Incidence of anencephaly in Jamaica. AB - Information was collected on 2,197 stillbirths and neonatal deaths on the island of Jamaica during the 12 month period September 1986 to August 1987 as part of the population based nationwide Jamaican Perinatal Morbidity and Mortality Survey. There were 14 cases of anencephalus giving an incidence of 0.26 per 1,000 total births. One of these cases was associated with the amniotic band syndrome; excluding this, the incidence would be even lower (0.24 per 1,000). There was no apparent association with social class, maternal age, or parity. The rate found in Jamaica is considerably lower than found in any other national population study. PMID- 2321162 TI - Timely monthly surveillance of birth prevalence rates of congenital malformations and genetic disorders ascertained by registries or other systematic data bases. AB - In many jurisdictions large data sets on malformations are now collected routinely in order to define prevalence rates of malformations in infants and children, to detect long-term secular trends, and to ascertain cases for ad hoc case-control studies. With slight modifications, these data sets may be used for prompt surveillance of changes in the birth prevalence of malformations, changes that conceivably could be possibly due to the introduction of a teratogen into the environment. A specific logistic approach is suggested, modeled on the New York State Malformation Registry, for prompt detection of changes in rates. PMID- 2321163 TI - Histological and in vitro studies supporting decreased uteroplacental blood flow as explanation for digital defects after administration of vasodilators. AB - In a recent study, the vasodilating drugs nifedipine, nitrendipine, felodipine, and hydralazine induced phalangeal defects in rabbits, when given on day 16 of pregnancy. Histologically, the changes were characterized by disturbed chondrogenesis. In order to elucidate mechanisms behind the defects, the fetal concentration of felodipine was measured, and the fetal limb plates were examined histologically, at 0, 2, 4, 8, 12, and 24 hours after single oral administration of felodipine (12 mumol/kg) on day 16 in pregnant rabbits. The effects of nifedipine, nitrendipine, and felodipine were also investigated in an in vitro system, in which chick embryonic mesenchymal limb bud cells differentiated into chondrocytes. In this system, no inhibition of chondrogenesis was observed below concentrations 3 x 10(5) M. At this concentration, unspecific cytotoxicity was found. The highest fetal concentrations of felodipine were more than 500 times lower than what was required for in vitro toxicity. Histologically, the digital areas of the limb plates showed extensive edema and dilatation of marginal sinus within 2 hours. After 8 hours, rupture of the thin-walled vessels occurred with hemorrhages. Finally, small necroses and blisters were observed. Similar early changes have been reported in experiments where digital defects were induced by clamping uterine vessels. This study thus indicates that the phalangeal defects after administration of high doses of vasodilators are secondary to pharmacological action (associated with a significant reduction in the uteroplacental blood flow), and not a direct effect on fetal chondrogenesis. PMID- 2321164 TI - Strain difference of the mouse in manifestation of hydrocephalus following prenatal methylmercury exposure. AB - Genetic background may influence susceptibility to hydrocephalus. In the present experiment we compared the manifestation of hydrocephalus following prenatal methylmercury exposure among strains of mice which sporadically develop or never develop spontaneous hydrocephalus. Pregnant mice of the B10.D2 congenic strain were given a single oral dose of 10 mg/kg methylmercuric chloride on one of days 14 through 17 of pregnancy and allowed to give birth and rear their litters. The incidence of grossly apparent hydrocephalus in the offspring at 30 days of age following treatment on day 14, 15, 16, or 17 of pregnancy was 67, 88, 75, and 48%, respectively; that of sham-treated and untreated offspring was 5 and 4%, respectively. In addition, there were some brains showing slight dilatation of the lateral ventricles. Pregnant females of C57BL/10 (B10) or DBA/2 (D2) strain were also treated with 10 mg/kg methylmercury on day 15 of pregnancy. The incidence of hydrocephalus at 30 days of age in untreated and dosed B10 mice was 0.8 and 54%, respectively. Hydrocephalus failed to develop in D2 mice. The hydrocephalus is a communicating type. Occlusion of the cerebral aqueduct with glial reaction and caudal displacement of the cerebellum are considered to be secondary changes. The results indicate that the susceptibility to methylmercury induced hydrocephalus is under genetic control in mice. PMID- 2321165 TI - Studies of methotrexate-induced limb dysplasias utilizing a 51chromium release assay. AB - The folate antagonist methotrexate (MTX), widely used in chemotherapy, is a well documented teratogen. However, the mechanism by which it exerts its effects is still unclear. Specifically, we have examined the cytotoxicity of MTX in vivo and in vitro and have looked at the relationship between cytotoxicity and teratogenesis. The chick embryo was utilized to examine the effects of the drug administered to carefully staged embryos. Embryos were exposed at stages 18-22 and examined on day 11 of incubation. Wings were malformed in a stage-dependent manner while legs were affected similarly at each stage used. A modification of the 51chromium-release assay was used to test the toxicity of MTX to limb cells in vitro. None of the tissues tested showed measurable toxicity in vitro even though the drug kills cells in vivo, thereby suggesting that MTX may be metabolized differently in vitro. Malformations induced by MTX do not seem to be due to changes in the amount of cell death taking place in the limb but may be caused by a transient inhibition of cell division. PMID- 2321166 TI - Relationship of DNA damage and embryotoxicity induced by 4 hydroperoxydechlorocyclophosphamide in postimplantation rat embryos. AB - 4-Hydroperoxydechlorocyclophosphamide (4-OOHdeCl-CP) is a preactivated analogue of cyclophosphamide (CP) that undergoes an elimination reaction to yield acrolein and the nonalkylating derivative of phosphoramide mustard (PM), i.e., dechlorophosphoramide mustard. We used this analogue to assess the role of acrolein in CP-induced embryotoxicity. Embryotoxicity was assessed using day 10 rat embryos cultured in vitro. 4-OOHdeC1-CP was embryotoxic over a concentration range of approximately 75-150 microM and produced complete embryolethality at concentrations of 175 microM and above. This analogue induced abnormal development characterized by tail defects at low drug concentrations and microencephaly or prosencephalic hypoplasia at high concentrations. Using the technique of alkaline elution, we also assessed DNA damage induced by embryotoxic concentrations of drug. When embryos were cultured in serum-containing medium during drug exposure, no DNA damage was detected, even at embryolethal drug concentrations. However, if cellular glutathione (GSH) was depleted with buthionine sulfoximine (BSO) before drug exposure and embryos were cultured in serum-free medium during drug exposure, DNA damage, primarily DNA single-strand breaks, was detected, but only at embryolethal concentrations. Using radiolabeled CP, we showed that acrolein does reach the embryo; however, more acrolein is incorporated into the yolk sac. Binding studies revealed that acrolein binds preferentially to cellular protein, whereas PM binds preferentially to DNA. These results suggest that, unlike the case with PM, the embryotoxic target for acrolein is protein and not DNA. Furthermore, our results indicate that acrolein may mediate its effects on the embryo via the yolk sac. PMID- 2321167 TI - Trisomy 13 in the fetus. AB - A significant number of fetuses with trisomy 13 are spontaneously or voluntarily lost before birth; however, very few such fetuses have been systemically autopsied. In the present study, ten trisomy 13 fetuses of 130-305 mm in crown rump length, estimated gestational age from 108 days to 239 days, were examined following either karyotype or ultrasonographic diagnosis and voluntary termination. Mean maternal age was 35.1 years. The spectrum of anatomical features was similar to that observed in neonates or older infants with trisomy 13, namely, holoprosencephaly, cyclopia, microphthalmia, cleft palate and lip, cardiac defect, polydactyly, and cystic kidney. Kidney weights were significantly increased above normal in eight of nine fetuses. Histologically, the cortex of these kidneys showed increased mitotic activity and blastemic appearance, which extended deep into the medullary areas. The weights and histology of other organs were normal except for slight increases in spleen weight. PMID- 2321168 TI - Comments on "Proposed Mechanisms of Action in Thalidomide Embryopathy". PMID- 2321169 TI - Comments on "Proposed Mechanisms of Action in Thalidomide Embryopathy". PMID- 2321170 TI - Organized nursing makes strides to ease shortage. PMID- 2321171 TI - Morphological integrity of the bronchial epithelium in mild asthma. AB - In severe asthma bronchial epithelial cells are damaged and detached, and it has been proposed that such damage might lead to the bronchial hyperresponsiveness that characterises asthma. To investigate the relation between airway hyperresponsiveness and epithelial damage, biopsy specimens of the bronchial mucus membrane were obtained at fibreoptic bronchoscopy from 11 patients with mild atopic asthma and airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) less than 1.0 mg/ml), and from 17 healthy non-atopic subjects who did not have airway hyperresponsiveness (PC20 methacholine greater than 8.0 mg/ml). Observers who were blind to the presence or absence of asthma examined the biopsy specimens by light and electron microscopy. Epithelial cells, intercellular spaces, and goblet cells were counted. Intercellular junctional complexes were examined, and a semiquantitative assessment was made of ciliary loss, non-parallel central ciliary filaments, and vacuoles in ciliated cells. There were no differences between the asthmatic and healthy groups in any of these measurements. These findings indicate that airway hyperresponsiveness may be present when there is no apparent change in the structure of the bronchial epithelium. PMID- 2321172 TI - Decline of the lung function related to the type of tobacco smoked and inhalation. AB - Data from a five year follow up study on 4372 smokers and 3753 non-smokers were analysed to investigate the influence of the type of tobacco smoked and whether the subjects said they inhaled or not on the decline in forced expiratory volume in one second (FEV1). The study sample comprised 1492 smokers of plain cigarettes and 1936 smokers of filter cigarettes, 1711 smokers of cheroots or cigars, and 233 male pipe smokers. Over the five years, smokers, especially those who said that they inhaled, had a higher rate of decline of FEV1 than non-smokers, in whom the average decline in FEV1 was 25 ml/year for women and 30 ml/year for men. There was no significant difference in the decline in FEV1 between filter cigarette smokers and plain cigarette smokers. The decline in FEV1 in cigar or cheroot smokers was the highest for all the smoking groups, and associated with a very high tobacco consumption in this group. Among pipe smokers who inhaled, the decline in FEV1 was slightly higher than in the cigarette smokers, whereas non inhaling pipe smokers had a decline in FEV1 that was similar to that of non smokers. In general, the smokers who said that they did not inhale had a smaller decline in FEV1 than those who said that they did. The effect of inhalation varied in magnitude in different smoking groups, being most pronounced in pipe smokers. PMID- 2321173 TI - Effects of passive smoking on the pulmonary function of adults. AB - The effects of exposure to environmental tobacco smoke (passive smoking) on pulmonary function of non-smoking, healthy Iranian men (n = 167) and women (n = 108) were investigated. There were significant reductions in % predicted FEV1 (5.7%), forced vital capacity (FVC, 4.6%) and forced expiratory flow 25-75% (FEF25-75, 9.9%) among men exposed to cigarette smoke (n = 78). The adverse effect of passive smoking was greatest among men exposed at the workplace (reduction in % predicted FEV1 9.4%, FVC 7.6%, and FEF25-75 15.3%). No significant difference in pulmonary function was found among the 54 women exposed to passive smoke, but only eight women had smoke exposure at work. It is concluded that exposure to environmental tobacco smoke, particularly at the workplace, adversely affects the pulmonary function of adults. PMID- 2321174 TI - Immunosuppression by pulmonary surfactant: mechanisms of action. AB - Pulmonary surfactant has been shown by this group to suppress peripheral blood lymphocyte responses to mitogens and alloantigens in a dose dependent manner, though the mechanism of action of the suppressive effect is not clearly understood. To try to clarify this, attempts were made to reverse the effects of preincubation with surfactant, obtained by bronchoalveolar lavage from pigs, on lymphocytes and accessory monocytes obtained from the blood of normal volunteers, by washing and incubating the cells in medium alone for various periods up to 24 hours. Immunosuppression, measured as the reduction in thymidine incorporation in response to the mitogen phytohaemagglutinin, could not be reversed by these methods. The addition of indomethacin (up to 100 micrograms/ml for 72 hours) also had no effect, indicating that the immunosuppression was not related to synthesis of prostaglandins. Incubation with surfactant for as little as two hours before addition of mitogen suppressed in vitro lymphoproliferative responses by half, but surfactant added two hours after mitogen had no observed effect. Preincubation of purified lymphocytes in surfactant, before they were cultured with accessory monocytes and mitogen, caused significant suppression of response, but preincubation of purified monocytes had no suppressive effect. There was no change in the intensity of HLA-DR expression on monocytes. These results support the hypothesis that surfactant exerts its effects on the resting uncommitted lymphocyte rather than on antigen presenting monocytes. PMID- 2321175 TI - Decline of lung function and development of chronic airflow limitation: a longitudinal study of non-smokers and smokers in Busselton, Western Australia. AB - Data collected during seven population health surveys over 18 years in Busselton, Western Australia, were examined to determine the effect of smoking on lung function and to investigate the development of chronic airflow limitation. Lung function was measured and details of respiratory illness and smoking histories were collected from subjects attending surveys at three year intervals from 1966 to 1984. Data from ex-smokers and asthmatic patients (diagnosis based on answer to questionnaire) were excluded. Regression of height adjusted forced expiratory volume in one second (FEV1) on age was calculated individually for 759 non smokers and 225 regular smokers with four or more observations. Decline in height adjusted FEV1 was similar for men and women. In smokers the rate of decline in FEV1 was greater than in non-smokers and was related to the amount smoked, to the extent that a smoker could expect a 20-30% greater rate of decline than a non smoker of the same age. Chronic airflow limitation (defined as FEV1/FEV less than 65% or FEV1 less than 65% predicted on at least two occasions) was common, occurring in 24% of men and 18% of women who were regular smokers and in 5% of male and 8% of female non-smokers. These figures are higher than those reported in other populations, especially for women and for non-smokers. Not all chronic airflow limitation was associated with respiratory symptoms, confirming that the condition may be unrecognised until it is advanced. PMID- 2321176 TI - Effect of fibreoptic bronchoscopy on pulmonary function. AB - Several studies have shown that after fibreoptic bronchoscopy there may be a deterioration in lung function but it is not known whether this is due to the premedication, the topical anaesthetic, or the obstruction produced by the bronchoscope. The effects of each part of the procedure on spirometric measurements were studied in patients with lung disease and in normal non smokers. Measurements were made after premedication (papaveretum and atropine) in seven patients and after topical anaesthesia of the bronchial tree (340 mg lignocaine) with and without the bronchoscope in the trachea in 21 patients and 10 control subjects. Premedication had no effect. In the normal subjects lignocaine produced significant falls in FEV1, forced vital capacity (FVC), peak expiratory flow (PEF), and peak inspiratory flow (PIF), and insertion of the bronchoscope caused further falls that were also significant. In the patients, however, although anaesthesia produced significant falls in FEV1, FVC, PEF, and PIF of similar magnitude to those found in the normal subjects, there was no further important decrease when the bronchoscope was inserted. It is concluded that the major effect of bronchoscopy on lung function is due to topical lignocaine in the airways, and in patients with lung disease (excluding asthma or a central obstructing carcinoma) the insertion of the bronchoscope causes little additional obstruction. PMID- 2321177 TI - Mycobacterial infection in patients infected with the human immunodeficiency virus. AB - Of 207 homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS), 24 with the AIDS related complex, and 39 with asymptomatic HIV infection, 32 patients were found to have mycobacterial infection. Mycobacterium tuberculosis was found in 13 patients with AIDS and in two with the AIDS related complex. M avium-intracellulare was found in 15 patients with AIDS and was disseminated in 12. One patient was infected with M kansasii and one with M ulcerans. Invasive procedures were frequently required to obtain positive bacteriological results. Subclinical carriage of M avium-intracellulare and other mycobacteria thought to be nonpathogenic was common in patients seronegative for the human immunodeficiency virus and at all stages of human immunodeficiency virus infection. All but one isolate of M tuberculosis were fully sensitive to standard antimycobacterial antibiotics. Response to treatment was usually rapid. M avium-intracellulare isolates were all resistant to first line agents in vitro, and antibiotics such as ansamycin and amikacin were required to obtain a clinical response. PMID- 2321178 TI - AIDS and UK respiratory physicians: attitudes to confidentiality, infection control, and management. AB - Respiratory physicians are concerned in the management of most patients with AIDS. Attitudes and practices of 463 respiratory physicians in the United Kingdom in relation to confidentiality, infection control, and treatment were sought by questionnaire from December 1987 to March 1988; 266 replies were received. Thirty eight per cent of respondents had not seen an HIV positive patient at the time of the survey. Respiratory physicians followed General Medical Council guidelines in relation to consent and confidentiality, except that if the patient's consent was withheld three quarters of the physicians would still inform an at risk hospital health care worker; only a quarter, however, would inform an at risk spouse. Routine infection control was frequently inadequate and "disease specific"--that is, substantially increased for known HIV positive patients. Given an HIV positive patient with respiratory symptoms and an abnormal chest radiograph, two thirds of respiratory physicians said that they would treat empirically for Pneumocystis carinii pneumonia as opposed to immediate bronchoscopy for accurate diagnosis. If a patient with AIDS who had pneumocystis pneumonia developed respiratory failure, half the physicians said at that time that they would elect not to ventilate the patient. PMID- 2321179 TI - Haemothorax caused by a solitary costal exostosis. AB - A case of spontaneous haemothorax in a 14 year old boy due to trauma to the diaphragm caused by a solitary benign growth (exostosis) of a rib is described. PMID- 2321180 TI - Diffuse meningeal thickening associated with pleural mesothelioma. AB - A case of pleural mesothelioma with diffuse spinal meningeal thickening as shown by magnetic resonance imaging is reported. PMID- 2321181 TI - Necrotising pneumonia and empyema due to Clostridium perfringens complicating pulmonary embolus. AB - A fatal case of necrotising pneumonia due to Clostridium perfringens developing as a complication of pulmonary infarction is reported. PMID- 2321182 TI - A case of necrobacillosis. AB - A case of empyema due to Fusobacterium necrophorum infection is described. A history of sore throat followed by metastatic abscesses may alert the clinician to the possibility of this unusual infection. PMID- 2321183 TI - Obstructive sleep apnoea due to a dermoid cyst of the floor of the mouth. AB - A case of obstructive sleep apnoea is reported that was caused by a dermoid cyst of the floor of the mouth and cured by surgery. PMID- 2321184 TI - Effect of chest physiotherapy on oxygen saturation in patients with cystic fibrosis. AB - Decreasing arterial oxygen saturation has been reported in patients with cystic fibrosis during postural drainage when this was combined with other manoeuvres, which did not, however, include thoracic expansion exercises or pauses for relaxation and breathing control. When these features were included in an active cycle of breathing techniques during postural drainage in 20 patients with cystic fibrosis there was no fall in arterial oxygen saturation during the procedure (mean values 87.1%, 87.9%, and 86.7% before, during, and after treatment). PMID- 2321185 TI - Fall in peak expiratory flow during haemodialysis in patients with chronic renal failure. PMID- 2321186 TI - Disturbance in respiratory mechanics in infants with bronchiolitis. PMID- 2321187 TI - Topical nasal anaesthesia for fibreoptic bronchoscopy. PMID- 2321188 TI - Adverse effect of additional weight on exercise against gravity in patients with chronic obstructive airways disease. PMID- 2321189 TI - Serum leucine-enkephalin in bronchial carcinoma and its relation to tumour location. AB - Serum concentrations of the opioid peptide leucine-enkephalin were measured by radioimmunoassay in 30 patients with histologically confirmed bronchial carcinoma and 10 control subjects. This peptide, which is present in greatest amounts in the central and autonomic nervous systems, has previously been found in bronchial neoplasms. The mean serum concentration of leucine-enkephalin was significantly greater in the patients with carcinoma (1035 pg/ml) than in the control subjects (426 pg/ml). In the 23 patients with a tumour in non-apical regions of the lung, however, the mean concentration of the peptide (422 pg/ml) did not differ significantly from that in control subjects; serum concentrations in the seven patients with an apical neoplasm (mean 3050 (range 1259-5820) pg/ml) were significantly greater than values in either the control subjects or the patients with non-apical lung tumours. All seven subjects with an apical tumour had one or more features of Horner's syndrome and the three with all four components of the syndrome had the highest serum concentrations. Serum concentrations of leucine enkephalin were unrelated to tumour type or presence of metastatic disease. No patient had evidence of metastases in the central nervous system or adrenal glands. Raised serum concentrations of leucine-enkephalin in patients with an apical tumour probably reflect invasion of cervical sympathetic ganglia with release of the peptide into the circulation rather than elaboration of the peptide by the neoplasm. PMID- 2321190 TI - [Surgery without blood transfusion]. PMID- 2321191 TI - [Heart surgery without blood transfusion]. AB - Blood conservation in open heart surgery has become mandatory in order to reduce the risk of viral contamination, and because of limited resources. We have performed 100 consecutive coronary artery bypass operations (13 women/87 men, aged 33-73 years, mean 58 years) without using homologous blood. A strict blood conservation programme was applied, with removal of autologous blood prebypass for retransfusion at the end of surgery, retransfusion of the heart-lung machine content to the patient, and autotransfusion of shed mediastinal blood in the postoperative period. All patients survived the operation and were extubated 1.6 hours (0-6) postoperatively. No patients needed resternotomy for bleeding, and no homologous blood was given. Five patients received 1-2 units of fresh frozen plasma because of coagulopathy. Mean hemoglobin was 12.0 g/100 ml and mean hematocrit was 36% at discharge from hospital. Elective coronary artery bypass surgery can be performed with little or no transfusions of homologous blood. PMID- 2321192 TI - [Penetrating abdominal injuries]. AB - We have reviewed the medical records of 111 patients treated for abdominal stab wounds during the period 1980-87. Our two hospitals serve a catchment area of about 450,000 people. Exploratory laparotomy was performed in 89 patients with suspected peritoneal penetration. In 16 patients the laparotomy was negative, and in 15 patients only minor injuries were noted. There were no serious complications in these 31 patients. Twenty-seven patients had thoracic wounds below the fourth intercostal space, 15 with intraabdominal injuries. The most common injuries were lacerations of the liver, the small bowel and the diaphragm. The mortality in the series was 2%. Stab wounds are infrequent in Norway, and most surgeons have limited experience of such injuries. We discuss whether to employ immediate exploratory laparotomy or selective management when the peritoneum has been penetrated. When there is no evidence of evisceration or omental protrusion, local exploration of the wound should be performed in order to confirm or exclude peritoneal penetration. Injury to the diaphragm and intraabdominal viscera should always be suspected in thoracic stab wounds below the fourth intercostal space. PMID- 2321193 TI - [Diagnostic peritoneal lavage in blunt abdominal trauma]. AB - Peritoneal lavage was performed in 142 of 331 patients submitted to hospital after blunt abdominal trauma. The lavage catheter was introduced through a short infra-umbilical longitudinal incision with surgically controlled access to the peritoneal cavity. First time lavage was positive in 58 out of 68 patients in demand of laparotomy, and after repeated lavages in 66 of 68. In 12 patients there was a false positive lavage. The sensitivity was 97% and the specificity 84%. Negative lavage strongly indicates that laparotomy is not necessary. A positive test as an indication for laparotomy should be regarded with reservation. The method is simple to perform and represents a valuable supplement to clinical evaluation in patients with blunt abdominal trauma. PMID- 2321194 TI - [Helicobacter pylori infection among employees at the gastroenterologic section, Haukeland Hospital]. AB - Using the C-14 urea breath test we estimated the gastric urease activity among 46 healthy Norwegians, all employed at the section of gastroenterology, Haukeland Hospital, Norway. The overall prevalence of Helicobacter pylori-infection (30.4%) is similar to that reported previously among healthy subjects outside hospitals. The tendency towards higher prevalence among the gastroenterologists (41.7%) may be accounted for partly by the preponderance of males in this profession. The results do not support the notion that gastroenterologists are more liable to attract gastric H pylori-infection than other hospital personnel. PMID- 2321195 TI - [Clinical neuropsychological investigation and personality assessment in alcohol abuse]. AB - In Norway, clinical neuropsychology is approved as an exclusive speciality in psychology. Clinical neuropsychological assessment is a well-proven method for which thorough validation studies and international norms are available. The method has a clear application in the assessment of dysfunctions and resources of alcohol-dependent inpatients. Cross-national comparisons show that neuropsychological findings are fairly consistent for alcohol-abusing individuals. A neuropsychological frame of reference is essential for secondary prevention among important groups. Some areas of central interest include alcohol and drug abuse among the elderly, occupational exposure to solvents, impulsiveness and violence, residual Attention Deficit Disorders, HIV/AIDS conditions, and other neuropsychiatric conditions. PMID- 2321196 TI - [Somatic symptoms in alcohol abusers' families]. AB - The families close to the abusers attending Borgestadklinikken for treatment appeared to be suffering from psychical and psychosomatic diseases. This was discovered at the beginning of an eight-week programme of treatment. The main somatic symptoms were dorsal pain, headache, and gastrointestinal, gynecological and cardiovascular symptoms. PMID- 2321197 TI - [Diagnostic peritoneal lavage in blunt abdominal injuries]. PMID- 2321198 TI - [Pharmacies' information pamphlets--what use are they to the patients?]. AB - Information pamphlets about certain drugs on prescription have been distributed to patients by Norwegian pharmacies since 1985. A questionnaire distributed to 500 patients, answered by 48.2%, showed that most patients liked to receive the pamphlets and 85.5% found them useful. However, it was difficult to evaluate the influence of the pamphlets on the patients compliance with instructions on how to use the drug. Many patients found the pamphlets difficult to understand. Most problems were connected with interactions with other drugs etc. Only 8.3% of the patients thought that other drugs might interact with the drug prescribed. The pamphlets were only one of several sources of information to the patients. The study showed that physicians informed the patients more about the effects (67.2%) than about the side-effects (49.4%) of drugs. Only 47.7% of the patients had received the pamphlets earlier. However, this percentage varied for the three participating pharmacies, being 20.2, 62.2 and 78.0% respectively. PMID- 2321199 TI - [Pharmacies' information pamphlets--do physicians know about them?]. AB - Information pamphlets for certain drugs on prescription have been distributed to patients by pharmacies since 1985. A questionnaire was sent to 50 general practitioners. Only 45.2% knew about the pamphlets. However, they were satisfied with this practice of spreading information. Most physicians did not object to others giving information about the drugs, but some emphasized that the informer must have adequate knowledge of drugs. The physicians had not received many questions from their patients in connection with the pamphlets. Most of the questions received were about side-effects. Many physicians thought that the pamphlets motivated patients to better compliance with instructions on how to use the drugs. Very few physicians gave written information to their patients. Most physicians wanted to cooperate with the pharmacies on information to patients. PMID- 2321200 TI - [Who uses A- and B-preparations? One year's registrations at the Vennesla pharmacy]. PMID- 2321202 TI - [Continuing education]. PMID- 2321201 TI - [Starting to smoke--vulnerability of girls]. AB - Smoking habits were highlighted in a longitudinal study of 1,230 secondary school students from the Oslo area. In the age group 16-19, 31% of the adolescents were daily smokers, rather more girls than boys. Most seem to start smoking between the ages of 12 and 15. These cohorts were selected for a closer analysis of the importance of modeling the roles of parents and peers. Both boys and girls copy their fathers' smoking habits, but girls also copy their mothers habits. For both sexes, parents' serving alcohol to their children strongly correlated with the childrens smoking habits. Reduced subjective well-being also seems to be important in the case of girls. The conclusion is that modeling roles on parents and peers is important for the development of smoking habits. Girls seem to be more vulnerable than boys to the influence of parents and peers, and there is also some evidence that girls often start smoking as a response to reduced subjective well-being. PMID- 2321203 TI - [The English disease]. PMID- 2321205 TI - [Malignant and premalignant lesions of the uterine cervix. Cytologic contribution to the diagnosis]. AB - A retrospective investigation covering the period 1980-84 showed that in 552 women the histological diagnosis was invasive or pre-invasive (CIN-III) lesion of the uterine cervix. The role of cervical cytology in the diagnosis was evaluated. Cytological smears had been taken from only 34% of women with invasive lesions as compared with 89% of women with pre-invasive lesions. False negative cytological diagnosis was submitted in 7%. In 38% of the patients the cytological smears brought to light less advanced changes than did the subsequent histological examination. Lack of endocervical cells in the smears gave less reliable material than when endocervical cells were present. The investigation gives grounds for the following recommendations: Women over the age of 45 should take greater advantage of the offer of having cervical smears taken. Women with even mild cytological changes must be controlled particularly if there are no endocervical cells present. Lack of endocervical cells in the smears should be reported. Cytological laboratories should send written reminders if requested repeat-smears or biopsies are not received. PMID- 2321204 TI - [Breast tumor--a diagnostic challenge]. AB - The study includes all patients referred for surgical examination with suspected breast cancer (n = 439) during a single year. All women were examined clinically. Mammography was performed in 372 cases (88%), and 195 (46%) women underwent biopsy. 37 (8.7%) of the admitted women had breast cancer, which was verified by histological examination. This corresponds to an incidence rate of 0.8 per 1,000 women, and an incidence rate of 2.0 per 1,000 in women above 40 years. In four patients who were not suspected as having breast cancer after clinical examination, breast cancer was revealed by mammography. However, mammography alone is insufficient, since three mammograms were false negative, in cases where cancers were diagnosed clinically. Therefore, both mammography and clinical investigation are necessary in the examination of women with breast tumors. When breast cancer cannot be ruled out by physical and mammographic examination, a representative specimen of the tumor should be removed for histological or cytological examination. PMID- 2321206 TI - [Delayed surgery in blunt abdominal trauma]. AB - Abdominal organ injuries caused by blunt trauma are notoriously difficult to diagnose, and for this reason an operation may be dangerously delayed. 426 abdominal organ injuries were registered in a series of 331 patients admitted after blunt abdominal trauma. 151 of these patients had 199 abdominal organ injuries which required surgical repair. In 31 patients (20%) with 44 organ injuries, operation was delayed for more than six hours after admission, in most cases because of missed diagnosis. One of these patients died as a result. Hollow viscus injuries were the most commonly missed. In addition to repeated clinical evaluation, peritoneal lavage, repeated if necessary, and diagnostic imaging must be used as valuable tools of diagnosis, especially in comatous patients, in patients with multiple injuries, and in intoxicated patients. PMID- 2321207 TI - [Restenosis after coronary angioplasty]. AB - Angiography of 169 patients who had been treated successfully with PTCA showed restenosis in 61. Of these, 38 were successfully treated with a new PTCA, and six developed a new restenosis. Restenosis usually appears during the first four months after PTCA in vessels with a diameter less than three millimeters. The authors emphasize the importance of careful clinical follow-up. PMID- 2321208 TI - [Hairy cell leukemia and Mycobacterium malmoense infection]. AB - We describe a patient with hairy cell leukemia and protracted fever. The patient's condition deteriorated during treatment with alfa Interferon 2b, and his fever persisted. A slight widening of the upper mediastinum appeared after 2.5 months. Mediastinoscopy with lymph node biopsy revealed granulomatous infiltrates with acid-fast bacilli. Cultures of the lymph node material later showed growth of Mycobacterium malmoense. The patient was treated with rifampicin, doxycycline, etambutol and cycloserin for sixteen months and remains afebrile and is gaining weight. His general condition is still improving. An aggressive diagnostic approach is necessary in febrile patients with hairy cell leukemia. PMID- 2321209 TI - [Mesenterial fibromatosis]. AB - The article presents a case of a rare tumor, mesenteric fibromatosis, unassociated with Gardner's syndrome and without previously abdominal surgery. The author reviews symptoms, diagnostic features and treatment, and discusses some of the possible differential diagnoses. PMID- 2321210 TI - [Analytically oriented group psychotherapy of patients with alcohol problems]. AB - The author discusses special problems which arise when working with analytic groups of alcohol abusers. The article focuses on different suggestions to group therapists for appropriate management of the treatment contract and of patients who drink while in therapy. PMID- 2321211 TI - [Follow-up of alcoholics. Inpatients at the Solhaugen Rehabilitation Center in 1985 and 1986]. AB - In this follow-up study 76 inpatient alcoholics who had stayed at a Treatment Centre for Alcoholism for at least 12 weeks were invited to participate. Five had died, seven were not found, and the remaining 64 were interviewed nine to 30 months after discharge. Laboratory tests for liver functioning were also obtained. Only one reported total abstinence, but 30 clients (47%) reported less drinking. Most of them had a better social and economic situation than before the period of treatment. PMID- 2321213 TI - [Central venous catheters]. PMID- 2321212 TI - [The difficult patient--or the difficult relation. Clinical use of the context concept]. AB - The difficult patient is a well-known character in the literature and in doctors' surgeries. We discuss the advantage of broadening the perspective from studying the qualities of the patient to studying the qualities of the therapeutic relationship. We underline the need to analyze not only the content of symptoms but also the meaning of symptoms in a wider relational context. The theoretical concepts are taken from systems-theory and the concept context is central. We stress the need to negotiate a context and common aims for therapy. PMID- 2321214 TI - [Adverse effects of non-steroidal anti-inflammatory agents on the central nervous system]. PMID- 2321215 TI - [Use of benzodiazepines. Abstinence phenomena and seponation strategy]. PMID- 2321216 TI - [Research training--the work situation of research trainees at the School of Medicine, University of Bergen]. AB - In an investigation in spring 1989 on research training at the Medical Faculty, University of Bergen, 111 questionnaires were returned of a total of 180 distributed. 35% of the trainees were satisfied with the training, 31% not, while 30% did not know as yet. Trainees who had been full-time research fellows for two years or more (n = 33), were split in two groups with different opinions. Half of them were satisfied with the training programme, and the other half were not. The most important factor linked with the trainees' opinion of the training was personal supervision. The satisfied ones were content with supervision they had received, whereas the unsatisfied ones were not. By and large, office and laboratory conditions were adequate for the trainees, but data equipment had been supplied by many of the trainees themselves. The overall impression of this investigation is that the research training programme is working fairly well, but there is remove for improvement in the supervision of the individual trainee. PMID- 2321217 TI - [Research training--what trainees think about future research education]. AB - A research training programme should have a clearly defined aim and a framework for accomplishment and contents. In Norway no such programme exists for the medical PhD. Present research training depends to a large extent on the individual student. The aim of this paper is to contribute to a discussion on the goals for a research programme and to report what research trainees and research fellows at the Medical Faculty, University of Bergen think is necessary as regards framework and content. 111 of 180 questionnaires were returned. On the average, the students preferred a research programme to last 4.0 years. 91 persons wanted the programme to contain a compulsory part lasting, on average, 5.5 months. The majority preferred no examination during this part of the programme. Most students wanted to maintain the present Norwegian standard for the medical PhD. PMID- 2321218 TI - [Organic versus non-organic diseases. A distinction necessary for rational practice]. AB - A great many, perhaps the majority, of those who see a doctor present subjective suffering and behaviour disorders that are problematic to classify as illness. This is because no pathobiological foundation for such classification is demonstrated--no matter how thoroughly the patients are examined, or how long they are followed up. Symptomatologically too, organic and non-organic conditions are distinctive. While organic illnesses are characterized by physical and biochemical signs, non-organic disorders manifest only distressing experiences (as pains or anxiety) or undesirable behaviour (as abuse of alcohol)--phenomena that are inseparable from normal sensation, emotion, intentions and actions. As for treatment, the main methods applied in organic illnesses are of a physical and biochemical nature. In cases of subjective suffering or behavioural deviances therapy consists of general relief, correction and sedation--all of the kind we make use of in our everyday lives. If the majority of those who consult a doctor are not really ill, what then, is the alternative? Individual and collective misery? The sole alternative to illness is normal psycho-physiological and behavioural variations. A widely held opinion, however, is that non-organic disorders fulfill the criteria for illness. This means that some kind of pathological substrate is postulated even when we fail to demonstrate its existence. The crucial point, however, is not to solve the problem of whether a person is ill or not, but to underline that we are dealing with two separate categories of phenomena - bio-pathologically and psycho-physiologically founded suffering and dysfunctioning. PMID- 2321219 TI - [Life with and without Halcion]. PMID- 2321220 TI - [Emergency medicine and telemedicine]. PMID- 2321221 TI - [Emergency care and primary routines in the treatment of severe injuries]. PMID- 2321222 TI - [Cholesterol measurement in general practice--Norwegian general practitioners' attitudes and estimation of their own practice]. AB - In 1988 a group of Norwegian experts published a programme for treatment of patients with increased cholesterol. The programme recommended dietary counselling when plasma cholesterol exceeded 5 mmol/l. In the autumn 1988 the Norwegian National Health Association started a campaign on cholesterol for health personnel. In order to find out to what extent general practitioners adhered to the recommendations of the programme, a random sample of 100 general practitioners were sent a questionnaire before and after the campaign. The results showed no significant differences in the doctors' attitudes towards diagnosis and treatment of patients with increased plasma cholesterol. Both before and after the campaign the plasma cholesterol levels at which they would initiate follow-up, dietary counselling or drug therapy were 1-2 mmol/l above the levels recommended by the expert group. The attitude of the general practitioners was more conservative than the recommendations of the programme. The interval between the information meeting and the post study was only six months. It is a complicated process to change attitudes and practice routines, and the time required may be longer than six months. Furthermore, the recommendations of the programme were questioned by other doctors, which reduced its impact. PMID- 2321223 TI - [Injuries caused by electricity]. AB - We review a patient material consisting of cases with electrical injuries submitted to Sentralsykehuset i Akershus, Norway over a period of ten years. 18 cases were treated during the period 1 January 1978 to 31 December 1987. All were men, with a mean age of 33 years. All injuries were caused by AC current; seven were low voltage, and 11 high voltage injuries. The low voltage injuries proved to be relatively innocent, but 2/11 with high voltage injuries died. Many of the high voltage patients had severe deep tissue, mainly muscular, damage. The two who died had respiratory arrest, were unconscious on admission and had cardiac arrest. Only one with cardiac arrest on admission and two with respiratory arrest survived; three of the five who were unconscious on admission survived. Optimal treatment of injuries caused by electricity requires a thorough understanding of the special pathophysiology of this condition. PMID- 2321224 TI - [Thyroid carcinoma and the recurrent nerve. Recurrence fall-out, incidence and causal circumstances in a large case-load of patients with thyroid carcinoma]. AB - Impairment of vocal cord function is a threat to patients with thyroid carcinoma; either due to the tumor having infiltrated the larynx or the recurrent nerve, or to accidental damage to the laryngeal nerves during thyroid surgery. We have reviewed 1,245 patients' records which were filed under the diagnosis of thyroid carcinoma at Det Norske Radiumhospital from 1956 to 1978. Pareses of vocal cords were noted in 465 patients (37.3%) during the course of their illness. In 135 patients (10.8%) the pareses were due to infiltration by the tumor, most commonly seen in anaplastic carcinoma. In 267 patients (21.4%) the pareses followed surgery; planned resections of the recurrent nerves were performed in 48 patients (3.9%). Transient pareses with normal vocal cord movements within months were experienced in 137 cases (11%). Permanent paralysis caused accidentally during surgery was seen in 82 patients, representing 6.6% of all patients and 4.7% of the surgically exposed nerves. We stress the need for pre- and postoperative evaluation of vocal cord movement as an aid to future diagnosis and optimal surgical planning. PMID- 2321225 TI - [Carcinoma of the adrenal cortex]. AB - We present nine cases of primary adrenocortical carcinoma, collected in our department of medicine and endocrinology over 25 years. In our patients, the most dependable tumor marker was urinary excretion of tetra-hydro-ll-deoxycortisol (THS), and elevated values were found in all cases where it was determined. In addition to surgical treatment, medication with o,p'-DDD was found to be of value for some of the patients. Median tumor weight was 487 g (118-2,085 g). Prognosis is difficult to predict. Median survival time after diagnosis was 34 months, but varied from three to 266 months. PMID- 2321226 TI - [Osteitis fibrosa cystica von Recklinghausen]. AB - We present the case of a woman with classical osteitis fibrosa cystica generalisata von Recklinghausen, caused by a single adenoma of the left inferior parathyroid gland. After six months with increasing bone pain, pathological fractures and cystic lesions radiologically, hyperparathyroidism was diagnosed by persistent elevated levels of serum calcium, and elevated levels of PTH. Surgical extirpation of the parathyroid adenoma caused a period with severe hypocalcemia followed by complete clinical restitution. The diagnosis should be considered in any case of persistent bone pain and uncharacteristic fatigue. PMID- 2321227 TI - [The extended self-care concept. Use of practitioners of alternative medicine and layman control of health services regarded as self-care]. AB - Research and discussions on self-care have been concentrated mainly on what happens before the patient decides to see a doctor. Attention could just as well be given to the forms of self-care used while the patient is under medical treatment, and perhaps even more to what self-care is used after the treatment has ended. Data from the Health Survey of 1985 indicate that patients who have seen a practitioner who practises alternative medicine are more likely to use a suitable form of self-care afterwards. This is supported by an interview survey of 150 patients who had visited such practitioners. The patients' attempts to influence the health system have to be regarded as a form of self-care. Many patients' organizations also function as centers which provide information about the quality of the practitioners. The extended health concept gives more authority to health personnel, the extended self-care concept gives more authority to the patients. PMID- 2321229 TI - [Education of medical students in substance abuse]. AB - A substantial amount of resources available to the health services in Norway are spent on alcohol- and drug-related disorders. Physicians play an important role in preventing, diagnosing and treating these disorders. We have reviewed the curricula used at our four Norwegian medical schools for education in this field. The curricula are characterized by lack of specified educational goals and are somewhat limited, seen in relation to the extent of the alcohol- and drug-related problems. With reference to a structured educational programme at Karolinska Sjukhuset, Stockholm, we propose a new Norwegian model for alcohol- and drug related medical education. This model focuses especially on early identification of problems and intervention in harmful alcohol consumption. PMID- 2321228 TI - [Evaluation of operant methods in the treatment of chronic pain]. AB - This article considers the principles of operant/social learning theory in the treatment of chronic pain. The authors emphasize the necessity of treating acute and chronic pain as two different conditions. They evaluate studies of behavioural treatment of chronic pain from the last decade, and conclude that although behavioural treatment of chronic pain seems effective, such conclusions are, in some cases, based on studies that are not methodologically sound. PMID- 2321230 TI - [Post-education in clinical problems of narcotics abuse]. AB - Since 1985 the Hjellestad Clinic, in cooperation with the Norwegian Directorate for the Prevention of Alcohol and Drug Problems, has offered five 40 hour courses a year for primary health care workers in order to provide them with the necessary knowledge dealing with drug- and alcohol-related issues in the local community. The focus is on early detection and simple intervention strategies. Since 1989 on we have offered two additional courses on special topics such as family, drug and alcohol problems, management of drug- and alcohol-related crises in the local community etc. The article discusses a new speciality in the "treatment of addictive behaviours". PMID- 2321231 TI - [Treatment of post-spinal headache]. PMID- 2321232 TI - [Day surgery--anaesthesiologic aspects]. AB - Adequate selection of suitable surgical procedures and patients is mandatory for good results in major ambulatory surgery. Proper information to the patients about pre-, per- and postoperative aspects is essential. Careful selection of anaesthesiological drugs and methods may provide safe, pain-free and comfortable anaesthesia; with a potential for discharge a few hours after the procedure. The article discusses these aspects. PMID- 2321233 TI - [Cisapride. A new agent which stimulates gastrointestinal motility]. PMID- 2321234 TI - [The cholesterol campaign--evaluation of a local action]. AB - As part of a Norwegian action to reduce cholesterol, we registered the names, addresses and cholesterol levels of 354 persons. In order to evaluate selected aspects of the campaign, we mailed a short questionnaire to all participants 1-2 weeks after the registration (the response rate was 94.9%). One out of five participants had a cholesterol level of 8 mmol/l or higher. Compared with the percentage in the general population, relatively few participants in the study were daily smokers. As much as 79% of the participants reported having benefited from the campaign. As a result of the campaign a majority reported being more motivated for dietary change. Participants with an education equivalent to compulsory school were most positive towards the campaign. 6% reported that, when told about their own cholesterol level, their immediate reaction, was one of fear. Those who were alarmed, and those with the highest level of cholesterol were as positive towards the campaign as those with lower levels of cholesterol. Persons with high cholesterol levels stated more often than others that they planned to change their diet. PMID- 2321235 TI - [The health consultant. A new profession]. AB - The facilitator is a new profession developed first in Oxfordshire in 1982 for the purpose of promoting prevention in primary health care. There are at present more than 100 facilitators in Britain and some in Holland, most of them working on prevention of cardiovascular disease, but recently some also in connection with the HIV-epidemic. In brief, the task of the facilitator is to bridge the gap or establish a new channel of communication between the general practitioner and his coworkers on the one side and the specialized health service on the other. The paper describes the tasks and working methods of the facilitator in some detail, particularly with respect to prevention of HIV-infection and control and care of HIV-positive and AIDS-sick patients in general practice. A trial project involving facilitators is planned in Oslo. PMID- 2321236 TI - [Occupational health care, coordination with primary health care]. AB - Occupational health care is a privately financed health service offered to the healthiest part of the population. It is not governed in the same way as primary health care. In this paper we conclude that the present model of organization is inadequate. The entire responsibility for organization of occupational health care should be placed with the Ministry of Health and Social Affairs. This will ensure efficient use of resources. PMID- 2321237 TI - [Log book registration of farms for slaughtering pigs in the Integrated Quality Control Project. I. Use of drugs and vaccines]. AB - Log book recording was done for twelve months on approximately 100 pig finishing farms in an Integrated Quality Control (IQC) project. This recording was designed to gain a better understanding of the extent and nature of the medication and vaccination on these farms. Vaccination against Aujeszky's disease was done on the majority of farms. This vaccination mainly consisted in a single, frequently intramuscular, injection. Vaccinations against swine influenza and infections due to Actinobacillus (Haemophilus) pleuropneumoniae were merely sporadic. The animals were dewormed in 58 per cent of the finishing periods, whereas they were given preventive treatment for sarcoptic mange in 23 per cent of the finishing periods. Not a single pig was treated with antibiotics and/or chemotherapeutic agents in 12.5 per cent of the finishing periods. The majority of finishing periods in which treatment was not carried out, were those having closed pig herds. To the extent that the farms were supplied with piglets by more breeders, there were fewer finishing periods during which treatment was omitted. The great majority of cases in which individual therapy was given, were treated for respiratory disorders. On 27 per cent of the farms, more than 10 per cent of the animals per finishing period were treated for respiratory disorders. Group medication was much less frequent: intestinal disorders did not have to be treated on 31 per cent of the farms, and 16 per cent did not require treatment for respiratory disorders. In the great majority of cases in which group treatment was required, this was given during the first sixty days of the finishing period. In view of the fact that there are marked differences in the degree to which pigs have to be medicated on the farms, recording the use of veterinary drugs on farms, could fulfil the function of a signal. On the basis of these signals, measures may be suggested in herd management programmes to ensure an effective and minimum use of veterinary drugs. Using a log book will also enable the pig farmer to estimate whether groups of animals may be sent to the slaughter-house without involving risks to public health. PMID- 2321238 TI - [Marketing in veterinary practice; a theoretical framework]. AB - An increase in the number of veterinarians, while at the same time the number of animals has remained constant, has resulted in growing competition. By extending the range of products and by enlarging the veterinarians' scope of activities this competition can be decreased. A marketing-orientation will be helpful in this respect. This article indicates in which way marketing concepts can be used in a veterinary practice. The services of the veterinarian will be looked at by means of the Abell approach. This focuses on the functions performed by the services and examines, per function performed, for whom this might be interesting and which alternatives there might be. Next the concept of market segmentation is filled in for a veterinary practice by means of a hypothetical example. The marketing mix (product, place, price, promotion and personnel) is given considerable attention. The last element of marketing in a veterinary practice that is discussed here is the marketing information system. In a next article the question will be answered how marketing-directed the Dutch veterinarian works nowadays. To find this out research has been done; 166 vets were interviewed by telephone for approximately 40 minutes each. PMID- 2321240 TI - [Good perspectives for welfare-friendly housing systems]. PMID- 2321239 TI - [Influenza or equine herpes virus (EHV)?]. PMID- 2321241 TI - [Veterinary Chief Inspection for Public Health. Reorganization of the Veterinary Inspection for Public Health a fact as of 12-9-1989]. PMID- 2321242 TI - Effects of divalent metals on the isolated rat glomerulus. AB - Glomerular changes are prominent in metal-induced nephrotoxicity, and the glomerulus may be a primary site of damage in some cases. In order to separate direct effects of metal ions from those occurring secondary to systemic or post glomerular toxicity, we have studied the effects of divalent salts of Hg, Cd, Cu, Zn, Mn, Ni and Co on several metabolic parameters in freshly isolated rat glomeruli. The concentration of the metal ion causing a 50% reduction in the incorporation of [3H]leucine into protein over 16 h varied from 30 microM with Cd to about 2 mM with Ni and Mn. The log of the concentration was significantly correlated with the softness of the metal ion, indicating greater toxicity of ions such as Cd2+ and Hg2+ that prefer sulphur as a ligand. Incorporation of [3H]sulphate into proteoglycans was affected in a comparable manner to total protein synthesis. However, the softer metals caused a preferential decrease in the production of more highly charged dermatan sulphate, indicative of an effect on mesangial cells. Glomeruli were found to contain about 50 fmol each of glutathione upon isolation, and this value decreased with time. However, Cd and Zn caused increases in total glomerular glutathione, and this phenomenon was inhibited by buthionine sulphoximine, indicating that synthesis of new glutathione was responsible for the increases. These studies demonstrate the usefulness of the isolated glomerulus for investigating mechanisms of nephrotoxicity, and indicate that the mesangial cell may be a preferred target for some metal ions. PMID- 2321243 TI - Differential effects of 12-O-tetradecanoylphorbol 13-acetate on cytochrome P-450 dependent monooxygenase activities in rat hepatoma cells: induction of P-450I and suppression of P-450II. AB - We have studied the effects of the tumor promoter 12-O-tetradecanoylphorbol 13 acetate (TPA) on cytochrome P-450-dependent monooxygenase activities in several differentiated and dedifferentiated Reuber rat hepatoma cell lines using aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH), ethoxyresorufin O-deethylase (EROD), and aldrin epoxidase (AE) as test systems. The following results were obtained: (1) Exposure of cultures to 400 nM TPA for 18-24 h increased AHH activities in the differentiated lines 2sFou, H41IEC3/G- and Fao as well as in the dedifferentiated line 5L, 1.5-2.5-fold. The phorbol ester did not affect AHH activity in the dedifferentiated line H5. (2) EROD, a marker for P-450I, was induced by the phorbol ester to a similar degree as AHH. (3) A monoclonal antibody directed against P-450I strongly inhibited the AHH activity induced by TPA. (4) The onset of AHH or EROD induction by TPA was much later than that elicited by benz[a]anthracene. (6) In contrast to the induction of AHH and EROD, TPA decreased AE activity, a marker for P-450II, by about 50% in all the cell lines containing this monooxygenase activity. (7) The half-maximum-effect concentration of TPA for inducing or suppressing AHH and AE, respectively, was approximately 20 nM. (8) TPA did not interfere with AHH induction by benz[a]anthracene. However, the phorbol ester moderately decreased AHH induction and markedly suppressed AE induction by dexamethasone. The results indicate that TPA simultaneously induces P-450I and suppresses P-450II forms in rat hepatoma cells. P-450I induction by TPA in these cells did not appear to depend on their status of differentiation. Furthermore, the results suggest that the mechanism of P-450I induction by TPA differs from that elicited by polycyclic aromatic hydrocarbons or glucocorticoids. PMID- 2321244 TI - Inhibitory effects of benomyl and carbendazim on the [3H]thymidine incorporation in various organs of the mouse--evidence for a more pronounced action of benomyl. AB - The benzimidazole fungicides benomyl and carbendazim were compared with regard to effects on [3H]thymidine incorporation in various organs of male mice given the compounds orally at various time intervals before sacrifice. Since carbendazim is a major metabolite of benomyl, it is generally assumed that the fungicidal action and toxicity of these compounds are due to the action of carbendazim. However, whereas benomyl inhibited the [3H]thymidine incorporation into thymus, spleen, liver, kidney and testis, an equimolar amount (3.4 mmol/kg body wt) of carbendazim induced a similar effect only in testis. PMID- 2321245 TI - Cocaine hepatotoxicity in cultured liver slices: a species comparison. AB - Studies were carried out in order to find a sensitive in vitro model with which to investigate cocaine-mediated hepatotoxicity. Precision-cut liver slices were prepared from: human, domestic pig, New Zealand white rabbit, Sprague-Dawley (S/D) rat, and two mouse strains (DBA/2Ha and ICR). The rationale for the choice of these species was that information on in vivo effects of cocaine was available in the literature. Slices were cultured for up to 6 h in the presence of 0-5 mM cocaine. Indices of toxicity consisted of K+ retention and Ca2+ uptake. Minimal effects and no clear dose-response relationships were observed. In addition to the studies with non-pretreated animals, liver slices were prepared from DBA/2Ha and ICR mice, both induced by housing on pine shavings, and phenobarbital pretreated Sprague-Dawley rats. The induced ICR mouse and rat were approximately 3 times more sensitive to cocaine-mediated hepatotoxicity. The following order of sensitivity to cocaine-mediated hepatotoxicity was established: induced rat = induced ICR mouse much greater than induced DBA/2Ha mouse = rabbit = uninduced ICR mouse = uninduced DBA/2Ha mouse = uninduced rat greater than pig = human. PMID- 2321246 TI - Cellular cadmium responses in subpopulations T20 and T27 of human lung carcinoma A549 cells. AB - Subpopulations T20 and T27, cloned from the human lung carcinoma line A549, differ significantly in their Cd2+ cytotoxic response. T27 has an LC50 of 31 microM Cd2+ and a cytotoxic response threshold of 5 microM Cd2+, whereas the T20s LC50 is 15 microM Cd2+ and there is no observed threshold for cytotoxicity. Cadmium-induced metallothionein (MT) synthesis, cadmium accumulation, glutathione (GSH) content, and Cd2(+)-induced changes in GSH content were studied in T20 and T27 in an attempt to determine the mechanism(s) causing differential cytotoxic response. MT synthesis measured by following Cd2(+)-induced [35S] incorporation into MT was found not to differ between T20 and T27. There is, however, a difference in Cd2+ accumulation between the two subclones. T20 and T27 cells were exposed to 5 microM Cd2+ for different times or to different concentrations of Cd2+ for 8 h. The T27 subline, which is the more Cd2+ resistant, was found to accumulate significantly more Cd2(+)-both as a function of time exposed to Cd2+ and as a function of Cd2+ concentration. The two subpopulations were found to have comparable initial GSH contents, but showed different Cd2(+)-induced changes in [GSH] when the cells were exposed to 5 microM Cd2+. T27 cells maintained their GSH content following Cd2+ exposure but T20 cells showed a Cd2(+)-induced decrease in GSH content. The results indicate that the difference in Cd2+ cytotoxic response between A549--T20 and A549--T27 cells is not attributable to alterations in MT synthesis nor to a difference in initial GSH content. Relative Cd2+ cytotoxicity also does not in these cells correlate with relative Cd2+ accumulation. The fact that T27 cells accumulate more Cd2+ and yet are more Cd2+ resistant than T20 cells suggests that T27 cells have a much more effective non MT mechanism to handle intracellular Cd2+. This may involve different GSH metabolism and/or yet undefined molecular factors. PMID- 2321247 TI - Statement on assistive personnel to the registered nurse. Tri Council. PMID- 2321248 TI - Laser lithotripsy. The new stone age. AB - 1. Advancements in stone management focus on the ability to safely fragment urinary calculi into small pieces, permitting simple elimination or facilitating retrieval and extraction. 2. The coumarin pulsed dye laser offers a safe and minimally invasive alternative in the treatment of calculi not amenable to or safely treated by other fragmentation techniques. 3. No complications have been directly attributed to laser lithotripsy. 4. Understanding laser mechanics and the principles of laser photo-fragmentation will promote the safe and knowledgeable integration of this revolutionary technology into the perioperative care of patients with urolithiasis. PMID- 2321249 TI - Reflections on being an expert witness. AB - 1. Lawyers hire expert witnesses to give opinions as to whether the nursing care administered to the patient met the "acceptable standard of care." 2. The lawyer who offers testimony from a nurse expert must show that the witness is qualified to offer an opinion on the case being discussed. 3. Careful preparation for serving as a nurse expert witness includes reviewing the documentation of the case as well as published nursing standards. PMID- 2321250 TI - Advanced nursing practice. AB - Advanced OR nursing practice is emerging and the roles, responsibilities, relationships, and rewards are spread over preoperative, operative, and postoperative work units. The roles of the nurse in advanced practice are multidimensional: clinical, collegial, educative, investigatory, and administrative. Though the primary allegiance of the ANP is to nursing, she has a commitment and the skills to work collaboratively with other nurses and disciplines on the surgery team. PMID- 2321251 TI - Cover gowns and clusters explored. PMID- 2321252 TI - Methods to prevent dislodgement of externalized vascular access. PMID- 2321253 TI - Wrestling against the odds. PMID- 2321254 TI - Researchers go out to pasture for hemoglobin. PMID- 2321255 TI - Liability for understaffing: who is responsible? PMID- 2321257 TI - Observations and thoughts about the earthquake and its aftermath. PMID- 2321256 TI - Radioulnar transposition. Salvaging a shattered forearm. AB - 1. A forearm shattered by a close-range shotgun injury can be reconstructed by transposing the distal radius to the proximal ulna. 2. This surgery is considered when repair of the bones is impossible, but an effort at reconstruction is warranted as an alternative to amputation. 3. A successful forearm reconstruction not only saves the forearm, wrist, and hand, but restores a satisfactory cosmetic and functional result. 4. Because radioulnar transposition re-establishes the bony integrity, future reconstruction in the form of tendon transfers may be undertaken to improve hand and wrist function. PMID- 2321259 TI - Mpwapwa cattle: an Indo-Euro-African synthesis. AB - Mpwapwa cattle are a synthetic dual-purpose breed developed in the Livestock Production Research Institute at Mpwapwa in Tanzania. The breed has received about 60% of its inheritance from improved dairy breeds originating in the Indian subcontinent (Red Sindhi and Sahiwal), about 30% from African zebu breeds (Boran and Tanzania Shorthorn zebu) and the remaining 10% from European breeds (mainly Ayrshire). The breed comprises only about 1,000 animals in two major herds and is threatened by extinction. The following production parameters have been reported for the herd at the Livestock Production Research Institute, Mpwapwa: age at first calving 45.4 months; calving interval 447 days; lactation milk yield (short lactations deleted) 1,447 to 1,628 kg; daily gain 259 g; carcass weight of steers (four years) 229 kg. PMID- 2321258 TI - Helminthosis in goats in southern Tanzania: investigations on epidemiology and control. AB - Investigations were conducted in naturally infected goats to determine the main epidemiological factors related to gastro-intestinal nematode infections in southern Tanzania with a view to making appropriate recommendations for control. Faecal worm egg counts rose during the single rainy season and then fell to remain low during the dry season. The beneficial effect of an anthelmintic treatment after the rains was demonstrated in weaner goats under traditional management and this should form the basis of rational control. PMID- 2321260 TI - Experimental infection of N'Dama cattle with trypanosomes using Glossina palpalis gambiensis caught in the wild. AB - The transmissibility of trypanosome infection to N'Dama cattle by tsetse flies caught in the field was examined. Wild-caught Glossina palpalis gambiensis were transferred singly into small numbered cages and allowed to feed on 14 uninfected N'Dama cattle. Following a completed feed the tsetse were dissected and infection in the proboscis, the salivary glands and the gut was recorded. Each animal was bitten by a number of tsetse ranging from five up to 64 flies. Following dissection of the tsetse flies, seven of the cattle were found to have been bitten by a single infected tsetse, five by two, while the remaining two were each fed upon by three infected tsetse. The tsetse were harbouring either Trypanosoma vivax or a trypanosome species belonging to the Nannomonas subgenus or both species. The experimental animals were monitored daily over a period of three months for the appearance of trypanosomes in the blood and for antibodies in their sera. Other parameters such as body temperature, local skin reactions, packed red cell volume and weight changes were also measured. Trypanosomes were first detected eight days after the infective bite. Only five of the 14 cattle became infected, of which three had been exposed to a single infected tsetse fly. Trypanosoma vivax was detected in one animal, Trypanosoma congolense in two cattle and mixed infections of both species in the remaining two animals. These findings show that N'Dama cattle can become infected with trypanosomes through the bite of a single infected tsetse fly under field conditions. However, only five (possibly eight) of the 23 infected tsetse were able to transmit the parasites successfully. PMID- 2321261 TI - Tick-borne diseases of cattle in Paraguay. I. Seroepidemiological studies on anaplasmosis and babesiosis. AB - A serological survey was carried out in Paraguay to determine the prevalence of antibodies to Anaplasma marginale, Babesia bigemina and Babesia bovis. The results suggest that the parasites are widely distributed throughout the country with prevalence rates of 92% for A. marginale, 79% for B. bigemina and 71% for B. bovis. Epidemiological studies on calves demonstrated that initial infection with the three blood parasites occurs in most animals within the first nine months of life. It is likely therefore that most of the country can be considered as being enzootically stable with respect to anaplasmosis and babesiosis. PMID- 2321262 TI - Antibodies to Toxoplasma gondii from domestic animals in Malaysia. PMID- 2321263 TI - Treatment of bovine tropical theileriosis with buparvaquone. AB - The antitheilerial activity of buparvaquone in crossbred male calves, experimentally infected with Theileria annulata (Izatnagar isolate) has been tested. Animals were treated intramuscularly at the dose rate of 2.5 mg/kg1 body weight. A single dose of the drug administered during the phase of ascending parasitaemia cured all the infected calves while all the untreated infected control calves died. PMID- 2321264 TI - Pasture infestation with trichostrongyles of camels in the Butana area of eastern Sudan. PMID- 2321265 TI - Productivity of crossbred cattle on smallholder farms in southern Malawi. AB - A 10-year set of dairy records from a smallholder dairy scheme in the Republic of Malawi was analysed. Environmental and breed effects on the reproductive and productive parameters were evaluated. Age at first calving for 110, 1/2 Friesian and 55, 3/4 Friesian cows were 36.7 and 40.1 months respectively; calving intervals based on 432 and 145 records were 488 and 482 days; total lactation yields on 554 and 227 records were 1,950 and 2,452 kg. Geographical area of operation, parity of cow, year and month of calving and their interactions did not exert a significant influence on reproductive traits but significantly influenced milk production traits. Deficiency in feed supplies was believed to be a possible cause of problems in reproductive performance. PMID- 2321266 TI - Clinically useful measures to assess the effectiveness of treatments: hints for a proper choice with special emphasis on cancer research. AB - Several absolute and relative measures useful to assess the consequences of treatments in cancer research are presented together with statistical methods suitable for computing the pertinent confidence intervals. The relationship of these measures with the parameters of the regression models commonly used in the analysis of survival data is elaborated upon. Three examples are elaborated, and conditions of interchangeability of the measures are discussed in detail. Finally, suggestions for the choice of the measure most appropriate for a specified data set are given. PMID- 2321267 TI - MOv18 monoclonal antibody in diagnostic applications: capability to recognize the histotype of the original tumor. AB - Cells from 52 ascitic fluids and 28 abdominopelvic cavity washings, obtained from 46 ovarian cancer patients, 17 patients bearing malignancies of non ovarian sites and 17 patients with non-malignant ovarian diseases, were tested using 2 methods: traditional cytology and monoclonal antibody immunofluorescence. The immunologic test using the MOv18 MAb, raised against ovarian carcinoma, revealed immunoreactive cells in 83% of the 36 cytologically positive fluids and in one of the 8 negative fluids from ovarian carcinoma patients and in 18% of the 17 fluids from patients with non-malignant ovarian disease. Forty six cytologically positive ascitic fluids from malignant patients were analyzed in order to evaluate the ability of this MAb to identify the histotype of metastatic cells. Ninety-three percent (26/28) of the effusions from nonmucinous ovarian carcinomas contained MOv18-positive cells, whereas no reactive cells were found in cytologically malignant fluids from patients with ovarian tumors of other oncotypes or with carcinomas of non-ovarian origin. The MOv18 reagent, used as an adjuvant in cytological analysis, can help in the identification of the histotype of metastatic cells of unknown origin. PMID- 2321268 TI - Sensitization of chronic myeloid leukemia cells to adriamycin cytotoxicity by clofibrate. AB - Clofibrate (CPIB), an antihyperlipidemic agent, was employed as a drug response modulator in this study to evaluate its action, if any, on adriamycin (ADR) cytotoxicity in adriamycin insensitive chronic myeloid leukemia (CML) cells in vitro. Inhibition of (3H)-thymidine incorporation was used as a measure of DNA biosynthesis inhibition. A marginally toxic concentration of CPIB [0.001% (v/v)] was utilized to evaluate the cytotoxicity in CML cells exposed to ADR 5 and 10 micrograms/ml. A heterogeneous response was observed in 16 different CML blood samples, 9 samples displaying a synergistic, 3 an additive and 4 a less than additive inhibition of DNA biosynthesis when exposed to the combination of ADR and CPIB. The cytotoxic effect induced by ADR alone and in combination with CPIB was found to be irreversible. The data suggest that the cell membrane modulating drug CPIB is effective as an adjuvant to enhance the antiproliferative action of ADR. PMID- 2321269 TI - Breast cancer screening in an urban population in northern Italy. AB - A mammographic and clinical screening for breast cancer started in June 1987 in the Health District of Brescia, Northern Italy, including the town and 23 surrounding municipalities. This paper describes the organization and the results of the first 12 months of screening. Of 7791 invited women aged 50-60 years, 5217 (67%) agreed to participate. There was a trend for response rates to decline with increasing age and education. Of the 5217 women examined, 66 (1.3%) were referred for biopsy and 64 (1.2%) underwent this procedure. A histologically confirmed malignancy was found in 42 women, corresponding to a prevalence of 8.1/1000. Positive predictive value of the screening was 65.6%. Among the 42 breast cancers, 4.8% were carcinoma in situ and 42.9% invasive tumors up to 10 mm in size. According to the p-TNM classification, 92.9% of all cancers were either TIS or in stage T1, 4.8% were in T2 and one tumor was classified in T4. Lymph node involvement was assessed in 41 cases, and 71.4% of all cancers detected by screening were negative for lymph node metastasis. In comparison, the classification of tumors found in women of the same age group and living in Brescia, histologically diagnosed in the urban hospitals during 1986, one year before the beginning of the screening, was as follows: 7.1% carcinoma in situ, and 16.7% invasive tumors up to 10 mm in size. 38.1%, 2.4% and 2.4% of all tumors were in stages T2, T3 and T4 respectively. PMID- 2321270 TI - Hormones in male breast cancer. AB - Urinary levels of testosterone, 5 alpha-androstanediol, 17 hydroxycorticosteroids, pregnanediol, and circulating levels of testosterone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, prolactin, luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin, were measured in 10 male patients with breast cancer and in a suitable group of healthy controls. No difference, either in blood or in urine, was observed between the two groups in the hormonal levels. The lack of abnormalities in peripherally detectable hormones suggests that the well recognized hormone dependency of male breast cancer may be due to some endocrine imbalance in the central (diencephalic) regulation of the sex steroids pathway. Alternatively, abnormal response of breast tissue to normal hormonal stimuli might be hypothesized in these patients. PMID- 2321271 TI - Observer variation in mammary thermography: results of a teaching file test carried out in four different centers. AB - To evaluate observer variation in mammary thermography, a teaching file test of 159 thermographies was worked out by 4 senology centers. The evaluation of accuracy and the K index of variability demonstrated a significant variability among centers. The reliability of thermography in senology seems to be too poor for it to be able to direct any therapeutic decision, either diagnostic or prognostic. PMID- 2321272 TI - Serum bone GLA-protein in hypercalcemia of primary hyperparathyroidism and malignancy. AB - Serum bone GLA-protein, a modern and sensitive marker of bone turnover, was measured in 15 patients with primary hyperparathyroidism, 18 patients with hypercalcemia of malignancy, 41 patients with bone metastasis without hypercalcemia, and 29 healthy subjects. Serum bone GLA-protein was increased in primary hyperparathyroidism (17.6 +/- 3.9 ng/ml) and normal in hypercalcemia of malignancy (5.2 +/- 2.8 ng/ml; p less than 0.001 vs hyperparathyroidism) and in normocalcemic patients with bone metastases. In primary hyperparathyroidism parathyroid hormone correlated positively with urinary calcium excretion (p less than 0.05) and with urinary hydroxyproline excretion (p less than 0.001). The sensitivity of serum bone GLA-protein measurements in differentiating between primary hyperparathyroidism and hypercalcemia of malignancy was 91% and the specificity 84%. Thus this marker appears to be a useful tool for the differential diagnosis of hypercalcemias. PMID- 2321273 TI - Pulmonary carcinoid presenting as multiple subcutaneous nodules. AB - A 60-year-old female presented with a one-year history of multiple enlarging tender subcutaneous nodules. Initial biopsy demonstrated a poorly differentiated adenocarcinoma. Mammography showed multiple nodular breast lesions. After the patient failed to respond to tamoxifen, a second biopsy demonstrated a metastatic carcinoid tumor. Further search revealed a single small pulmonary nodule, which on aspiration biopsy proved to be a carcinoid tumor. The patient failed to respond to treatment with streptozotocin and 5'-fluorouracil. Therapy with leucovorin calcium and 5'-fluorouracil then produced a partial response. PMID- 2321274 TI - Liver glutathione contents in patients with gastric adenocarcinomas. AB - Many antineoplastic agents alter the reduced glutathione (GSH) status of liver and tumor tissue by inhibiting cellular GSH-linked enzymes. Thus, intracellular GSH plays an important role in a wide variety of antineoplastic interventions regarding therapeutic efficacy and toxicity. Mean GSH values were 0.791 +/- 0.072 mg/m wet weight (ww) and 0.719 +/- 0.047 mg/g ww in gastric cancer tissue and nontumorous glandular mucosa, respectively. Whereas, the average GSH level of normal gastric mucosa was 1.709 +/- 0.135 mg/g, the mean GSH level of normal liver biopsies was 2.378 +/- 0.260 mg/g. The GSH values of normal liver tissue were higher than the hepatocellular GSH concentrations of patients with gastric adenocarcinoma and of another group of tumor-bearing patients who had received chemotherapy preoperatively. These results suggest that the GSH levels of tumor and liver may influence the efficacy and/or toxicity of chemotherapeutic agents. PMID- 2321275 TI - A study of the pineal hormone melatonin as a second line therapy in metastatic colorectal cancer resistant to fluorouracil plus folates. AB - Since there is no effective second line chemotherapy in colorectal cancer resistant to fluorouracil, this study was carried out to evaluate the therapeutic activity of the pineal hormone melatonin, which has appeared to have antineoplastic activity in some experimental conditions, in patients with metastatic colorectal carcinoma who did not respond to fluorouracil. The study included 14 patients (8 men, 6 women; mean age 58 years). Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; after that, melatonin therapy was continued at 10 mg/day orally in responder patients, in those with stable disease and/or an evident improvement in PS. One patient had a minor response; 3 other patients had a stable disease, whereas the other 10 cases progressed. An evident improvement in PS was seen in 5/14 (36%) patients. These preliminary results show that melatonin does not have important antitumor activity in metastatic colorectal cancer patients resistant to fluorouracil. However, the pineal hormone could be usefully employed as supportive care to improve the quality of life in these patients for whom no standard treatment is yet available. PMID- 2321276 TI - Vinblastine and interferon-alpha-2a regimen in the treatment of metastatic renal cell carcinoma. AB - Thirteen patients with histologically proven advanced and/or metastatic renal cell carcinoma (RCC) were treated with vinblastine (Velbe, Eli Lilly, Sesto Fiorentino, Italy) and interferon-alpha-2a (Roferon-A, Roche, Milan). Eleven out of 13 patients were evaluable. Eighteen percent of patients had partial response, 46% stable disease (SD), and 36% progressive disease (PD). The mean survival of responders was 228+ days, whereas the patients showing SD and PD had a mean survival of 154+ and 107+ days respectively. Toxicity, including influenza-like syndrome, fever, neurological and gastrointestinal side effects, was generally mild. However, medication with paracetamol was required in 82% of cases. Our small study confirms that VBL and IFN-2a regimen is moderately active in RCC. PMID- 2321277 TI - In vitro reversal of doxorubicin resistance by the tiapamil analog RO 11-2933 in human ovarian cancer cells. AB - The ability of RO 11-2933 to restore cellular sensitivity to doxorubicin (DX) was investigated in cultured human cancer cells with two different levels of treatment-induced resistance to DX. In the poorly resistant subline A2780-DX1, a short-term (2 h) exposure to 1 microM RO 11-2933 (IC10) completely restored DX sensitivity, whereas in the more resistant subline A2780-DX3 only partial reversal of drug resistance could be achieved by this schedule of treatment. In these cells, a long term (72 h) exposure to 1 microM RO 11-2933 (IC15) or a higher dose (6 microM) given for 2 h was required to reverse DX resistance completely. Investigation of the effects of RO 11-2933 on DX cellular accumulation and retention indicated that RO 11-2933 was able to enhance DX accumulation and reduce DX efflux within resistant cells to levels comparable to those found in sensitive cells. PMID- 2321278 TI - Histochemical study of mucinous ovarian cystomas of intestinal and mixed types: O acetylated sialomucin content in relation to biologic behavior. AB - The subgroup of mucinous ovarian cystomas of intestinal type containing site 8 O acetylated sialomucins and its relation to malignant behavior were studied. Of 75 mucinous cystomas of the ovary from the files of the Institute of Pathological Anatomy and Histology (University of Genoa), 54 were endocervical, 19 were mixed, and 2 were intestinal. As regards their histologic pattern, the 54 mucinous endocervical cystomas were benign, whereas the 19 mixed type group included 8 benign, 5 borderline and 6 malignant; the 2 intestinal type tumors were borderline. According to histochemical investigations, the frequency of tumors with goblet cells containing site 8 O-acetylated sialomucins (positive to PB/KOH/PAS) was 47% in the mixed type cystomas and 100% in the intestinal type cystomas. Twenty-five percent of benign mixed cystomas, 60% of borderline mixed cystomas, and 67% of mixed cystadenocarcinomas were positive to PB/KOH/PAS. One hundred percent of the borderline cystomas of intestinal type were positive. Our results confirm that among mucinous ovarian cystomas, those containing intestinal type epithelium are the most likely to fall within the borderline or malignant categories. Moreover, of all ovarian cystomas of intestinal type, those characterized by site 8 O-acetylated sialomucins seem to be more aggressive and, in general, to have a more malignant behavior than the mucinous cystic tumors of mullerian or endocervical type. PMID- 2321279 TI - Alveolar soft part sarcoma of the vagina. AB - We describe a case of primary alveolar soft part sarcoma presenting as a vaginal mass in a 27 year old woman and also review the literature on this type of tumor arising in the lower female genital tract. Histologically, most of the tumor exhibited poorly developed alveolar architecture, but anaplasia was absent. Although the mass was well circumscribed, a few tumor cells were seen focally within the peritumoral tissue. Treatment consisted of wide local excision followed by external radiation therapy. The patient is alive without evidence of disease 17 years after operation. PMID- 2321280 TI - [Human experimentation--ethics, law]. PMID- 2321281 TI - [Kathon CG--a new contact sensitizing preservative]. AB - Kathon CG is a preservative, widely used in skin care products and cosmetics. Prior to introduction to the market, extensive studies on the sensitizing potential of this product were performed. The conclusion drawn from these studies was, that the risk of sensitization was extremely small, when used in concentrations below 15 ppm. Now, ten years later, the frequency of allergy to Kathon CG is 1-2% in the Danish population, which is in the same range as the frequencies for the other preservatives. It is concluded, that the preliminary studies were insufficient and monitoring of the prevalence rates of sensitization is important, when new potential sensitizers are introduced. A total ban on the isothiazolinone derivates from the cosmetics, will only transfer the problem to the other preservatives already known as sensitizers. It might be technically acceptable to lower the concentrations further. Since the cosmetic products are not declared, a correct diagnose may be delayed or missed in patients with eczema. Ingredient labelling should be required by the authorities. PMID- 2321282 TI - [Frequency of Chlamydia trachomatis in women under 35 years of age consulting the general practitioner for gynecologic or obstetric reasons]. AB - In a general practice, we examined 173 women under the age of 35 years who sought help for gynaecological or obstetric reasons, consecutively. 18% of all of the examinations for Chlamydia rendered positive results. Chlamydia infection was commonest in the younger age groups. The case histories and objective findings were unsuited for predicting which of the patients had Chlamydia infection. Routine examination for Chlamydia is recommended in women under 25 years in general practice. PMID- 2321283 TI - [Permanent, percutaneous osseointegrated titanium implants. A review and preliminary results]. AB - The present knowledge of the requirements for obtaining a stable percutaneous bone-anchored implant is reviewed. A Swedish implantation system, developed by Branemark et al, is presented. The implants are made of titanium and the special design and manufacturing in combination with atraumatic operation technique in two stages assure that the implants are osseointegrated without interposed fibrous tissue. Soft tissue problems around the skin penetration are few and in most cases reversible. In the first seven Danish patients, implanted with the Branemark-system for fixation of bone anchored hearing aid, stable osseointegration was achieved in all cases, judged clinically, radiologically and by 99mTc-methylene-diphosphonate scintigraphy of the cranium. In two cases brief, reversible soft tissue problems were present. The system has been shown to be most useful in otological rehabilitation, for fixation of bone-anchored hearing aids, and for fixation of prostheses of the external ear, eye or mid-face. The Branemark-system has also been used in orthopaedic surgery, so far, however, only as endoprostheses, in particular for reconstruction of metacarpophalangeal joints. PMID- 2321284 TI - [Bone-anchored hearing aids. Preliminary results]. AB - The bone conduction hearing aid is employed for patients who cannot tolerate treatment with air conduction hearing aids and for whom operation cannot offer permanent improvement of hearing. Conventional bone conduction hearing aids are, however, uncomfortable to wear, amplification is frequently less effective and sounds are often distorted. A new type of bone conduction hearing aid, the bone anchored hearing aid (BAHA) is presented. In this, sound is transferred directly to the cranium via a percutaneous titanium implant. The results of treatment of the first six Danish patients are presented after a therapeutic period of 8-24 months. The subjective effect of treatment was satisfactory in all of the patients. They all employed their BAHA all day and found that the effect was better than the effect of air conduction hearing aids and conventional bone conduction hearing aids on practically all points. Speech discrimination investigations in quiet and noisy surroundings confirmed the subjective assessment although the differences between BAHA and the two other types of hearing aids were not as great as the patients subjective impressions. The bone anchored hearing aid, BAHA, should, in our opinion, become the bone conduction hearing aid of the future for patients who have a permanent need for this. It represents considerable progress in treatment of a group of patients for whom treatment has hitherto been difficult and unsatisfactory. PMID- 2321285 TI - [Schoenlein-Henoch syndrome with acute scrotal condition simulating torsion of the testis]. AB - A boy aged six years with Schonlein-Henoch's syndrome developed pain and considerable swelling of the right half of the scrotum. Emergency exploration could exclude torsion of the testis and revealed vascular changes in the testis and epididymis. Scrotal complications of Schonlein-Henoch's syndrome are rare but may occur as the initial symptom. The condition may be difficult to differentiate from torsion of the testis and emergency exploration may be necessary. PMID- 2321286 TI - [Disseminated intravascular coagulation and pneumococcal septicemia after splenectomy]. AB - Two cases of fulminant pneumococcal septicaemia are reported. These occurred 18 and 25 years after splenectomy. These patients had not received pneumococcal vaccination. Disseminated intravascular coagulation developed early and was of decisive significance for the course of the illness with lethal issue. The characteristic clinical picture in pneumococcal speticaemia in asplenic patients may be misinterpreted initially as influenza and meticulous observation is therefore necessary and antibiotic treatment according to current guidelines should be initiated as early possible in febrile episodes. PMID- 2321287 TI - [Abscess of the omental bursa (lesser sac)]. AB - Subphrenic omental bursa abscess is frequently overlooked and the overall mortality is 70%. Early diagnosis and drainage improve the prognosis considerably. In cases with abdominal symptoms followed by pyrexia, possibly with signs of sepsis, and pleural effusion but with no or only slight findings on objective clinical examination, subphrenic abscess should be suspected and a scanning of the abdomen should be performed. PMID- 2321288 TI - [Splenic rupture--a skateboard accident]. AB - A 13-year-old boy presented with persisting abdominal pain after a skateboard accident. Primary clinical and laboratory findings disclosed no signs of intra abdominal bleeding. Ultrasound scanning indicated rupture of the spleen which was confirmed by acute exploratory laparotomy. PMID- 2321289 TI - [Paranoid symptoms caused by cerebral metastasis]. AB - Cerebral tumours occasionally present with psychiatric symptoms. A case is described of a man aged 60 years with a cerebral metastasis and a clinical picture of intermittent neurological symptoms and paranoia. PMID- 2321290 TI - [Ileocolic invagination with anal presentation. Differential diagnosis of anal prolapse]. AB - In cases of anal prolapse in infants, intussusception should be considered in the differential diagnosis as the apex of the intussusception may present per annum even in cases with brief histories and no change in the general condition. PMID- 2321291 TI - [Research and priorities]. PMID- 2321292 TI - [Allergic manifestations caused by nickel hypersensitivity in women with a copper intrauterine device]. PMID- 2321293 TI - [The significance of the environment for delivery at a special department]. AB - A material of 292 normal pregnant women was subdivided at random for delivery either in the traditional delivery room or a newly established environmental room. The alterations in the physical environment of delivery did not result in more numerous spontaneous deliveries. A high frequency of episiotomies, stimulation of contractions and artificial deliveries in primiparae occurred particularly when it is considered that two thoroughly investigated groups of low risk pregnant women were concerned. However, qualitative differences in the experience of the course of delivery were found in favour of the environmental room. The quality of the experience of delivery did not depend so much on the physical environment but more on contact with the staff members responsible for conduct of the delivery. PMID- 2321294 TI - [The reliability of fiber endoscopic estimation of the size of gastroduodenal ulcer]. AB - The areas of 22 regions in a gastro-duodenal model were estimated endoscopically by 11 examiners. The procedure was then repeated with a biopsy forceps as the reference for measurement. Without the biopsy forceps, 86% of the areas were underestimated. Measurement with the biopsy forceps reduced the deviations of the estimates and the scatter of these but 75% were still underestimated. The estimates showed considerable inter-observer variation and limited reproducibility. Endoscopically estimated alteration in area of an ulcer should not be accepted as clinical documentation for healing. PMID- 2321295 TI - [Diet and health. A survey of diet and health in women 40-50 years of age]. AB - During the period 1980-1986, the Housekeeping Committees of the Danish Rural Institute carried out individual investigations of the diets of 513 women aged 23 50 years. Out of these, 124 were in the age group 40-50 years and this group was selected for health investigation. A Danish version of the Cornell Medical Index questionnaire with 138 enquiries about current and previous health conditions was sent to the 108 women who agreed to participate. All of these were visited in their homes by a doctor who reviewed the replies to the questionnaire and collected supplementary information for use in the diagnostic history. Only few cases of diseases of civilization were found and there were no cases of cancer. The current state of health was assessed summarily on the basis of the number of affirmative replies in the questionnaire. A statistical connection was found between the state of health and the combination of the fat-energy percentage and the vegetable roughage in the diet. PMID- 2321296 TI - [Injuries or diseases of the ear, nose and throat encountered at a casualty department. A one-year caseload]. AB - All of the casualty department records for the period 1.1.1987-31.12.1987 from the Casualty Department in Frederiksberg Hospital were reviewed, a total of 25,064. 4.7% or, 1,183 of these concerned injuries or disease in the ear, nose or throat. The frequency of attendances on account of ear, nose and throat injuries or disease was found to be 1.08% for persons resident in the municipality of Frederiksberg. The total material consisted of 55.5% boys or men and 44.5% girls or woman. 24% were in the age group 0-14 years and 15.2% 70 years or more. Attendances in June to August for these conditions were significantly fewer. 20.1% of the cases were brought to hospital by ambulance. Violence was involved in 6.9% of all the cases of ear, nose and throat conditions. Epistaxis was the commonest diagnosis and comprized 14.8% of all cases of ear, nose and throat conditions. The next commonest diagnoses were contusions of the face, head and neck which comprized 10.8% and these were followed by fracture of the nose with 7.2%. These were followed by otitis media which occurred particularly frequently in children like pseudocroup and foreign bodies in the nose. 10% were referred for x-ray examination via the casualty department. 10.8% were admitted and, in addition, 38.6% were examined or followed-up in the Ear, Nose and Throat Department. 12.3% were referred to their general practitioners and 3.6% to practising ear, nose and throat specialists. PMID- 2321297 TI - [Treatment of alcoholics based on the control principle. A prospective study of therapeutic results]. AB - The results of a psychotherapeutic inpatient treatment for alcoholism using the goal of increased control of drinking are reported. The patients participating and the outcome of the first 18 months after treatment are presented. Eighty-six patients participated in the treatment and between 78 and 71 of these could be followed-up. Before the treatment the great majority of the patients drank in accordance with the diagnosis addictive alcoholism. The mean duration of alcohol problems was nine years and the first therapeutic contact had taken place six years ago. The results are compared with the situation on admission and the 12 month period before treatment. After treatment, the mean daily alcohol consumption was nearly halved. About 3/4 of the patients reduced their drinking, half of the patients by more than 50% and 1/4 by more than 75%. Half of the patients drank less than six drinks per day, 1/3 less than four, and 1/4 less than three. The consumption showed a decreasing tendency during the 18 month period mainly due to an increase in non-drinking days. The patients' satisfaction with their mental condition, their relation to family and friends and life in general was greatly increased. The socio-economical problems were restored compared to the situation on commencing treatment but not to a level above the situation in the 12 months period before treatment. It is concluded that severely dependent alcohol abusers can be helped by psychotherapy with their mental or life problems and thereby increase control with their alcohol consumption. PMID- 2321298 TI - [Parotid tuberculosis]. AB - Two cases of tuberculosis in the parotid gland are presented. In both cases, the patients were submitted to operation on account of a suspected parotid tumour. Histological examination, revealed, surprisingly, tuberculosis. This is a rare form of extrapulmonary tuberculosis and only four cases were referred to the Tuberculosis Register in Denmark in 1988. PMID- 2321300 TI - [Postgraduate clinical education, tutorship]. PMID- 2321299 TI - [Seizures and opistotonus after propofol anesthesia. A possible connection]. AB - A case of repeated tonic-chlonic seizures and opisthotonus which developed after anesthesia with propofol (Deprivan) in a woman aged 43 years is described. The seizures continued for seven days despite antiepileptic therapy. On the basis of this case and other case reports, it is recommended that propofol should only be employed with reservation in patients with known epilepsy or predisposition to epilepsy. PMID- 2321301 TI - [Auricular perichondritis caused by acupuncture therapy]. PMID- 2321302 TI - [Health status in Greenland]. PMID- 2321303 TI - [Polyunsaturated fatty acid preparations available on the Danish market. Composition and oxidative stability]. AB - The emerging interest in essential polyunsaturated fatty acids has resulted in a number of products available in the Danish market. These products contain essential fatty acid oils rich in n-6 and n-3 fatty acids. The quality of these products plays a major role in planning prophylactic and clinical studies. This investigation therefore illustrates the quality and the contents of undesirable oxygenated compounds--peroxides and polymeric/oxidative components. Intake of these undesirable substances can theoretically contribute to the development of cancer. It is therefore of utmost importance to be aware of the quality of the product especially when relatively large doses are employed for a considerable period. Our results show that the oxidation values of the fish oil products are much higher than vegetable oils. Furthermore we observed higher amounts of polymerised/oxidised components in Pikasol although the peroxide value was relatively low. Okholm's fish oil and cod liver oil contain higher amounts of undesirable gadoleic and cetoleic acids. A quality control from the authorities is desirable as the consumer has only the producer's/importer's "assurances" to rely on and these are not always in accordance with the real facts. PMID- 2321304 TI - [Duchenne muscular dystrophy. Therapeutic principles and status after 14 years]. AB - Eighty-one patients with Duchenne muscular dystrophy (DMD) were included in a retrospective investigation involving the period 1975-1989 with the object of describing a therapeutic programme to prevent the sequelae of the disease and to illustrate the course of the disease in the treated DMD-patients. The therapeutic programme was carried out at home under the supervision of a physiotherapist with current control examinations by specialists in neurology, orthopaedic surgery, physiurgy, pulmonary medicine and anaesthesia. Employing the Kaplan-Meier principle of calculation, it was found that the median age for cessation of ambulatory function was ten years and the age of survival 22 years. The results suggest that a daily training programme which includes prevention of contractures postpones cessation of ambulation and prolongs survival. PMID- 2321305 TI - [Refugees' encounter with the Danish psychiatric system]. AB - Recently, Western clinicians have met an increasing number of victims of organized violence who, as political refugees, have sought asylum here. On basis of literature-studies and research carried out by the authors, the article gives an overview of present knowledge about the composition of the refugee population in Denmark, and the need of psychiatric/psychological assistance. The most common presenting symptoms of traumatized refugees are related to traumatic stress conditions, sometimes accompanied by acute outbursts of affect, psycho-somatic complaints, substance abuse or psychotic break-down. The relevance of the concept of Post-Traumatic Stress Disorder (PTSD) for the field of refugee treatment is briefly described, and possible offers of therapy, including Post-Traumatic Therapy (PTT), are discussed. Some immediate questions facing psychiatry are raised, the need of a co-ordination of treatment offers is pointed out, and directions for further development of clinical practice and research are proposed. PMID- 2321306 TI - [Pulmonary function and survival of patients with alpha 1-antitrypsin deficiency, residents of Copenhagen]. AB - From 1976 to 1987 alpha 1-antitrypsine deficiency type PiZZ was diagnosed in 89 patients living in the Copenhagen urban area (mean age: 45 years). Spirometry was performed yearly in 66 of these patients (mean observation period was 50 months). At the time of diagnosis basic FEV1 was significantly lower in smokers and ex smokers than in patients who had never smoked (45%, 44% and 84% of predicted normal, respectively). However, the decline in FEV1 was similar (3% per year) in all three categories of smokers. Our results indicate that both smokers and non smokers are at risk of developing pulmonary emphysema, however, the disease usually appears later in life or not at all in non smokers. PMID- 2321307 TI - [Screening methods for microalbuminuria in diabetes mellitus]. AB - Persistent microalbuminuria indicates early development of nephropathy, cardiovascular disease and death in patients with diabetes mellitus. In this study morning urines from 189 diabetic patients were investigated with conventional dip sticks, microbumintest and quantitative measurements obtained by immunturbidimetry. Microbumintest has both a higher specificity and sensitivity compared to urinary dip sticks. The immune chemical method is less expensive and alternations in albumin excretion rate can be followed. Quantitative measurement with an immunchemical method is therefore recommended as screening method for microalbuminuria. PMID- 2321308 TI - [Assessment of exposure to organic solvents. Reading the label or the legally compulsory instructions for use are not enough]. AB - A case history is quoted to illustrate the description of exposure to organic solvents and to illustrate the following points: 1) It is not possible to assess the degree of exposure qualitatively by registering of legally correctly written labels and instructions for use. 2) Quantitatively correct prescriptions of the products do not reflect the quantitative conditions of exposure and 3) Thermodynamic calculations which also consider how the individual components influence the rates of vaporization of one another can describe the conditions of exposure more precisely. PMID- 2321309 TI - [Occupational eye injuries]. AB - Occupational eye injuries are common. The authors found that these constituted 2.5% of all the injuries treated in the Central Hospital in Esbjerg during the period 1.8.1987-31.12.1987. A total of 224 patients were included in the investigation. Of these, 145 had not employed any form of protection of the eyes when the injury occurred. This was mandatory where 34% were concerned and not mandatory for 66%. Occupational eye injuries resulted in 0-4 days of sick-leave and young men were particularly affected. Metal workers were most exposed and unskilled workers employed with grinding and welding. Forty-five patients had sustained more than two occupational eye injuries within the past year. Twenty one of these had not notified any of the injuries, 11 had notified some of the injuries and 13 had notified all of the injuries. Approximately 80% had received instruction about employment of protective measures. PMID- 2321310 TI - [Limited-time admissions for observation at the Psychiatric Hospital for Children in Risskov during the period 1 January 1984-31 December 1986]. AB - The present article describes experience with admissions for observation for limited periods in the Psyciatric Hospital for Children in Risskov. Admissions of this type were introduced in 1984 in Risskov and this is hitherto the only place in Denmark where this is done. The case records of 75 children admitted during the period 1.1.1984-31.12.1986 were reviewed as regards the pattern of referral, the problems on admission and placing on discharge. The durations of these admissions were 4-5 weeks and the structure of these admissions for limited periods is described in this article. The value of this form of hospitalization is emphasized. Maintenance of the child's relationships to the home and school, efficiency of the working routine and improved sorting out of children for long term hospitalization are emphasized as important arguments. Finally, it is recommended that all departments for child psychiatry with residential units should have the possibility of admitting children for limited periods as part of extended outpatient investigation. PMID- 2321311 TI - [Acute thrombocytopenic hemorrhage as the initial symptom of infectious mononucleosis]. AB - A case of acute thrombocytopenic haemorrhage caused by infectious mononucleosis is presented. The differential diagnostic deliberations and the treatment are discussed. PMID- 2321312 TI - [Retroperitoneal location of a chordoma]. AB - A case of a retroperitoneal chordoma is presented. The observed localization without relation to the axial skeleton has not been reported previously. PMID- 2321313 TI - [Mortality in Greenland]. PMID- 2321314 TI - [Enuresis nocturna]. PMID- 2321315 TI - Correlation of tissue constituents with the acoustic properties of skin and wound. AB - The purpose of this study was to compare measurements of ultrasound properties of skin and wound tissue with measurements of material properties such as total collagen concentration, acetic acid soluble collagen concentration, water concentration, and morphologic properties. Using a scanning laser acoustic microscope (SLAM), both ultrasonic speed and attenuation coefficient values were obtained for control skin (2-3 cm from the wound), for skin immediately adjacent to wounds (within 0.3 mm), as well as for wound tissue itself. The attenuation coefficient and speed measurements were lowest for wound tissue followed by adjacent skin and then control skin. As the wounds healed there appeared to be an increase in both speed and attenuation coefficient although the wound age at which these increases started and the length of time for which they continued varied from one dog to the next. The precision of duplicate sample measurement of wave speed was +/- 1.7% for control skin, whereas that for attenuation coefficient it was +/- 16%. Both ultrasonic speed and attenuation coefficient were directly correlated with tissue collagen concentration and inversely correlated with tissue water concentration (p less than 0.001). Attenuation coefficient correlated best (r = 0.73) with acetic acid soluble collagen concentration which reflects the changes in collagen taking place during the repair process. These attenuation measurements made at 100 MHz using the SLAM were compared for control skin and wound samples with measurements made at 10-40 MHz using backscatter acoustic techniques (BAT). The tissue samples analyzed by each ultrasound technique were from adjacent locations on the animals. PMID- 2321316 TI - Time lapse and microscopic examinations of insonated in vitro cells. AB - A fibroblast cell line (Balb/c 3T3) was sham/exposed to ultrasound (2.2 MHz resonant frequency, 35.4 W/cm2 SPTP, 3 microseconds pulse duration, 200 Hz prf) for 30 min and subsequently scored for cell motility and alterations in cell morphology. Cell motility was assessed by computerized tracking of cells. Cell morphology ("normal" or "abnormal") was determined blindly by three independent scorers. A positive control (1-4 Gy) yielded statistically significant alterations in cell motility and morphology; no such differences were observed for the ultrasound regimen. The results thus fail to confirm an earlier report by Liebeskind et al. (Brit. J. Cancer 45(Suppl. V):176-186; 1982) of ultrasound induced alterations in cell motility and morphology. PMID- 2321317 TI - Electromyographic study of respiratory muscles during human diving at 46 ATA. AB - Electromyographic (EMG) recordings of the 6th to 7th intercostal space (thoracic EMG) and abdominal muscles, ventilatory pattern, and the work of breathing were studied in 4 human subjects exposed for 12 days to 46 ATA of helium-oxygen (density = 8.7 g.liter-1) then of nitrogen-helium-oxygen gas mixture (ternary mixture) (density = 11.1 g.liter-1). We found that the respiratory muscle work necessary for eupneic ventilation was multiplied by 4 at 46 ATA. During quiet breathing as well as during forced inspiratory maneuvers, the power spectrum of thoracic EMG shifted to the left in three individuals during the sojourn at maximal pressure, whichever gas mixture was inhaled. This was corroborated by the decreased ratio of EMG power in a high to that in a low band of frequencies. These alterations disappeared at the end of the decompression period, suggesting the existence of inspiratory muscle fatigue at high pressure. Hyperbaric tremor was recorded on the thoracic EMG and was maximal with He-O2 inhalation. It disappeared at the end of the period at 46 ATA (He-N2-O2). PMID- 2321318 TI - Prolonged whole body immersion in cold water: hormonal and metabolic changes. AB - To characterize metabolic and hormonal responses during prolonged whole body immersion, 16 divers wearing dry suits completed four immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 meters of sea water. One immersion began in the AM (1000 h) and one began in the PM (2200 h) to evaluate diurnal variations. Venous blood samples were obtained before and after completion of each immersion. Cortisol and ACTH levels demonstrated diurnal variation, with larger increases occurring after PM immersions. A greater than three-fold postimmersion increase occurred in norepinephrine (NE). There were significant increases in triiodothyronine (T3) uptake and epinephrine, but no change in T3, thyroxine, thyrotrophic hormone, and dopamine. Postimmersion free fatty acid levels increased 409% from preimmersion levels; glucose levels declined, and lactate increased significantly. Only changes in NE correlated significantly with changes in rectal temperature. In summary, when subjects are immersed in cold water for prolonged periods, with a slow rate of body cooling afforded by thermal protection and intermittent exercise, hormonal and metabolic changes occur that are similar in direction and magnitude to short-duration unprotected exposures. Except for cortisol and ACTH, none of the other measured variables exhibited diurnal alterations. PMID- 2321319 TI - Lack of diurnal effects on periodic exercise during prolonged cold water immersion. AB - Diurnal effects on periodic exercise were examined in 8 male divers wearing passive thermal protection during whole body immersions in 5 degrees C water for periods of up to 6 h. Studies were done during the course of 5-day air saturation dives at a depth of 1.61 ATA, with immersions beginning at 1000 h (AM) and 2200 h (PM). During each hour of immersion, leg exercise was done for 3 min each at workloads of 50, 70, and 90 W. Heart rate (HR) at each workload increased uniformly with immersion time, without a change in slope of HR vs. workload. No AM or PM differences occurred. AM resting VO2 increased linearly, and to the same extent as PM, with exposure time. VO2 at 50 W also increased at the same rate as resting values. VO2 at 70 and 90 W were similar for AM and PM and did not vary significantly during the 6-h immersions. Temporal increases in exercise HR may reflect cardiac compensation of diminished plasma volume. Workloads greater than or equal to 70 W generate enough metabolic heat in this specific condition to meet the thermogenic requirement. Lack of diurnal effects on exercise variables may be due to environmental conditions suppressing circadian rhythms. PMID- 2321320 TI - Inherent unsaturation in the treatment of pneumothorax at depth. AB - In discussing the treatment of pneumothorax under pressure, standard diving medicine publications recommend only the insertion of a chest tube before decompression. However, there are marked difficulties in performing surgery in a typical offshore commercial chamber, and present knowledge of chamber bacteriology indicates there is important risk of serious infection. By contrast, the venerable principle of inherent unsaturation and known experimental data permit the rational and safe use of pressure and oxygen breathing to resolve this problem. This should be the treatment of first preference for, even if it is not effective, no other options are closed off. Two representative cases are presented. PMID- 2321321 TI - A "Certificate of Added Qualifications" by the American Board of Preventive Medicine. PMID- 2321322 TI - Analysis of neurologic symptoms in deep diving: implications for selection of divers. AB - Eighteen professional divers (age range 24-33 yr, mean 28.3) participated in one simulated dive to 360 meters of seawater (msw) in a helium-oxygen (heliox) atmosphere with equal compression and decompression profiles. All divers were given an extensive neurologic examination before diving. Clinical neurologic symptoms observed during the dives were equilibrium disorder, sleep disturbances, fatigue, nausea, loose stools, stomach pain, tremor, mental disturbances, reduced appetite, and headache. Symptoms were scored individually by each diver. The symptoms were analyzed statistically by factor analysis, which grouped them into four factors. These symptoms are presumably related to functional disturbances in the brain stem and the cerebellum. Factor 3 symptoms (tremor, mental disturbances, reduced appetite) correlated significantly to a history of predive decompression sickness (P = 0.006) and to cerebral concussion (P = 0.023). Three divers were periodically unable to work at bottom due to equilibrium disorder, diarrhea, or nausea. One diver with mild polyneuropathy and slight cerebral atrophy as seen by computerized tomography and another diver with abnormal electroencephalography were periodically unable to work due to equilibrium disorder and nausea, respectively. We advocate that divers with signs of central or peripheral nervous system dysfunction should not be selected for deep diving. PMID- 2321323 TI - Synergist Erection System: clinical experience. AB - The Synergist Erection System (SES) was tested over a six-month period in 44 impotent patients with an organic etiology. The device was successfully used by 73 percent. The duration of erection for 75 percent of the patients was as long as they wanted to wear the device. The frequency of use was once a week for 47 percent. The quality of erection was rated satisfactory by 63 percent of the patients and 78 percent of the couples rated satisfactory intercourse. It appears the SES option is a valid one with high success and satisfaction rating at least on a short-term basis. In addition, it offers prophylactic protection. PMID- 2321324 TI - Clinical experience of Kock pouch continent urinary diversion. AB - Kock continent ileal reservoir for urinary diversion was performed in 53 patients with invasive bladder cancer (52) or neurogenic bladder (1). The postoperative follow-up period was from six to thirty-nine months. The clinical results showed no metabolic disturbance of blood electrolytes or acidity. Prolapse of efferent nipple valve developed in 4 patients (7.6%); and 2 underwent revisional surgery with a good result. Another 4 patients (7.6%) suffered from poor continence and relatively frequent catheterization to empty the pouch was necessary to prevent urine leakage through the stoma. Urodynamic study of the Kock pouch in these 4 patients showed a short functional nipple valve length and small pouch capacity. The other 45 patients (84.8%) had good continence. Urodynamic study of the pouch in 20 patients showed low pressure (mean of 13.3 cm H2O) in the pouch and high pressure (mean of 72.1 cm H2O) at the efferent nipple valve. Three patients had unilateral hydronephrosis in the follow-up intravenous urography. Corrective surgery for stenosis at the right ureteroileal anastomosis was done in 1 patient with normalization of the upper urinary tract afterward. The other 2 patients were managed by close observation for the mild hydronephrosis. Symptomatic bacteriuria developed in only 3 patients (5.7%) and responded well to antibiotic management. Reservoirography demonstrated no reflux into the upper urinary tract in all the follow-up patients. There was no significant change of the renal function at twenty-four months after operation detected by radionuclide (131I Hippuran) renal functional study. All patients were satisfied with Kock urinary diversion. PMID- 2321325 TI - Comparison of flow cytometry to routine testicular biopsy in male infertility. AB - We compared DNA flow cytometry to morphologic evaluation of routine testicular biopsies as methods of monitoring spermatogenesis. The study group consisted of 14 azoospermic men and 5 others who underwent testicular surgery unassociated with fertility problems. The findings for both studies were divided into three groups: normal, moderately abnormal, and markedly abnormal. Correlations between the findings from routine biopsy and flow cytometry were good. Of 9 patients having normal testicular morphology, 7 had normal ploidy classes by DNA flow cytometry while 2 had moderately abnormal histograms. Of 5 cases with moderately abnormal morphology, 1 had normal, 1 had moderately abnormal, and 3 had markedly abnormal ploidy distributions. In 5 cases described as Sertoli cell only, all DNA histograms were markedly abnormal, consisting almost exclusively of diploid cells. DNA flow cytometry of testicular biopsies and aspirates has been demonstrated to be a rapid, reproducible, and objective approach in evaluating the infertile male and is a promising method to investigate spermatogenesis in an outpatient clinic in lieu of formal testis biopsy. PMID- 2321326 TI - Techniques for outpatient hypospadias surgery. AB - With careful attention to patient selection and anesthesia, as well as easy-to manage dressings and urinary diversions, outpatient surgery for all degrees of hypospadias can be performed safely and economically. By using these techniques over an eighteen-month period all hypospadias operations were performed in the outpatient department. This included thirty-four minor operations as well as twenty-five major hypospadias repairs. Seven complications were encountered in the fifty-nine operations. PMID- 2321327 TI - Infundibulopelvic dysgenesis: a spectrum of obstructive renal disease. AB - Infundibulopelvic dysgenesis is an obstructive process of the pyelocalyceal system that is responsible for a spectrum of congenital renal disorders. The site and degree of narrowing in the infundibulopelvic system produce the various congenital anomalies like hydrocalycosis, calyceal diverticula, ureteropelvic junction stenosis, and multicystic kidney. A classification with illustrative cases is presented showing a common pathogenesis of these congenital obstructive anomalies. PMID- 2321328 TI - Chronic follicular pyeloureteritis. AB - A case of chronic follicular pyeloureteritis is presented. This rare lesion, not previously published in the American literature, must be differentiated from primary renal lymphoma and generalized malignant lymphoma of the nonHodgkin type. PMID- 2321329 TI - Postoperative spindle cell nodule of bladder. AB - We describe a new tumor of the bladder resembling sarcoma. The tumor typically develops after damage to the bladder wall, and the clinicopathologic features make it possible to recognize it as a benign lesion rather than the malignant lesions for which it can be mistaken. PMID- 2321330 TI - Solitary metastasis of renal cell carcinoma to urethra. AB - A case report of a solitary metastasis to the urethra from previously resected renal cell carcinoma is reported. The patient presented with total gross painless hematuria. We believe this is the first such case to be reported. PMID- 2321331 TI - Ureteroscopic removal of retained ureteral Double-J stents. AB - At the Lahey Clinic Medical Center, Double-J stents are placed primarily for management of patients with calculi. They are used before extracorporeal shock wave lithotripsy (ESWL) of large renal calculi or bilateral ESWL treatments and after ureteroscopic instrumentation or removal of calculi. They are also used for palliative urinary diversion for patients with ureteral obstruction secondary to pelvic cancer. Fluoroscopy with C-arm guidance is the standard radiologic technique employed for manipulation of all calculi and insertion of stents. Results have been good with the use of these stents, but in 3 patients the rigid ureteroscope was required to remove a retained Double-J stent. PMID- 2321332 TI - Content and distribution of vasoactive intestinal polypeptide (VIP) in cavernous tissue of human penis. AB - Penile erection is controlled by a valvular structure in the helicine artery in humans. The opening and closing of this valve are believed to be regulated by the autonomic nervous system, especially through the release of vasoactive intestinal polypeptide (VIP). We determined the content of VIP in cavernous tissue in 18 impotent patients and in 5 normal controls by radioimmunoassay, and we examined the distribution of VIP-ergic nerve fibers in cavernous tissue by an immunohistochemical method. As a result, it was found that the lower penile VIP content was more frequent among patients with organic impotence than among the controls. Furthermore, VIP-ergic nerve fibers were seen to be diffusely and loosely distributed in a large number of organic impotence patients. These findings suggest that organic impotence in some patients may be due to decreases in the VIP content and in VIP-ergic nerve fibers. PMID- 2321333 TI - New method to control dorsal vein complex during radical retropubic prostatectomy. PMID- 2321334 TI - Improved technique for hydrocelectomy in children. PMID- 2321336 TI - Nonsteroidal anti-inflammatory drugs facilitate stone passage. PMID- 2321335 TI - Transverse scrotal approach for insertion of AMS inflatable penile prosthesis. PMID- 2321337 TI - Use of long-acting oxytetracycline against pasteurellosis in lambs. AB - The efficacy of long-acting oxytetracycline in the control of pneumonic pasteurellosis in lambs was tested on seven Scottish farms. After laboratory confirmation of pasteurella-related deaths in lambs, half the lambs in each flock were given long-acting oxytetracycline (20 mg/kg intramuscularly) and half were left untreated. On three farms a single treatment was given and on four farms two doses were administered four days apart. Eighteen of the 878 control lambs died as a result of confirmed Pasteurella haemolytica pneumonia compared with one of the 878 treated lambs. In addition nine of the control lambs were diagnosed clinically to have pasteurellosis which responded to treatment with oxytetracycline. None of the treated lambs were seen to be ill during the trial. PMID- 2321338 TI - Haematological, biochemical and physiological changes in horses and ponies during the cross country stage of driving trial competitions. AB - The haematological, biochemical and physiological changes associated with the cross-country stage of driving trials were studied in horses and ponies competing in singles, pairs, tandems and teams at five, five-section and two, three-section events. Heart rates were monitored continuously and sometimes exceeded 200 beats/minute. The highest maximum, mean and recovery heart rates were found after the most severe competitions. Rectal temperatures were also highest after the most severe events and in some animals exceeded 41 degrees C. Respiratory rates were very variable. Blood taken five minutes after the cross-country showed a marked increase in haematocrit and a leucocytosis. Total plasma protein concentration increased by about 9 per cent but there was little change in the concentrations of plasma electrolytes. There was a very variable increase in plasma lactate concentration, the increase being related to the severity of the event; plasma lactate concentration occasionally exceeded 10 mmol/litre. Plasma glucose was also increased. The activities of plasma creative kinase and aspartate aminotransferase were only slightly increased after the cross-country stage. PMID- 2321339 TI - Haematology of clinically normal and sick captive reindeer (Rangifer tarandus). AB - A retrospective analysis of haematological values from clinically normal captive reindeer (Rangifer tarandus) showed that the red cell count, haemoglobin level, packed cell volume and lymphocyte count were higher and the erythrocyte sedimentation rate and eosinophil count were lower in juveniles than in adults. Newborn animals were anaemic compared with juveniles and adults and had high reticulocyte counts. The values from healthy reindeer were used to identify abnormal haematological variations in a number of sick animals. It was shown that reindeer exhibit similar haemopathological responses to those of other artiodactyla, with increases in the erythrocyte sedimentation rate and fibrinogen level being of particular diagnostic significance. Eosinophilia was the only abnormal haematological finding in individuals with subclinical infections of intestinal parasites. PMID- 2321340 TI - Transmission of encephalopathies. PMID- 2321341 TI - Casualty cattle. PMID- 2321342 TI - Diagnosis of ovine toxoplasmosis using PCR. PMID- 2321343 TI - Use of phenolic and chlorocresol disinfectants near dairy premises. PMID- 2321344 TI - Feline pinnal dermatitis. PMID- 2321345 TI - Vaccination during URT disease in kittens. PMID- 2321346 TI - Vaccines authorized for use in ferrets. PMID- 2321347 TI - Regional eosinophilic coloproctitis, typhlitis and ileitis in a dog. AB - A 3-year-old female Petit Basset Griffon Vendeen is presented with tenesmus alvi caused by a 15 cm long chronic regional cicatrising eosinophilic coloproctitis with bacterial masses surrounded by clubs, resembling actinomycosis. Similar changes were found in the caecum, next to a nodular eosinophilic inflammation in the ileal mucosa. PMID- 2321348 TI - Investigations on the role of flea antigen in the pathogenesis of German shepherd dog pyoderma (GSP). AB - Skin reaction patterns to the intradermal injection of a whole-body flea extract were examined in five physically healthy dogs and in 24 dogs with German Shepherd dog Pyoderma (GSP) at 15 and 30 minutes and at 1, 2, 4, 8, 24, 48 and 72 hours after the injection. In 10 out of 24 GSP dogs a positive skin reaction was observed macroscopically after 15 minutes. Delayed reactions at 24 or 48 hours were not observed. In the control group neither immediate nor delayed reactions were observed. The histopathologic skin changes were basically the same in both groups: an initial polymorphonuclear reaction followed by a mononuclear cell reaction. In the GSP dogs, however, these changes occurred earlier and were more prolonged than in the normal dogs. No flea-antigen-specific IgGd antibodies could be demonstrated by enzyme-linked immunosorbent assay. It is concluded that delayed type hypersensitivity to flea antigen does not play a role in the pathogenesis of GSP. Immediate type hypersensitivity may contribute to the disease in some cases. PMID- 2321349 TI - Investigations on the role of staphylococci in the pathogenesis of German shepherd dog pyoderma (GSP). AB - Skin reaction patterns to intradermal injections of a Staphylococcus intermedius antigen were examined in physically healthy dogs and in dogs with German Shepherd dog Pyoderma (GSP) at 15 and 30 minutes and at 1, 2, 4, 6, 8, 24, 48 and 72 hours after the injection. In both groups the skin histopathology revealed an aspecific inflammatory response of an early polymorphonuclear reaction, followed by a mononuclear cell reaction at 24 and 48 hours. It is concluded that hypersensitivity to staphylococcal antigens does not play a role in the pathogenesis of GSP. PMID- 2321350 TI - Comparative evaluation of the enzyme-linked immunosorbent assay (ELISA) in the diagnosis of natural Fasciola gigantica infection in cattle. AB - The enzyme-linked immunosorbent assay (ELISA) was evaluated for the diagnosis of naturally acquired Fasciola gigantica infection in cattle in comparison with conventional parasitological techniques. Using unfractionated whole worm extract of F. gigantica as the antigen, it was observed that there was a good correlation between ELISA positivity and positive diagnosis of fascioliasis by post mortem liver examination, bile egg sedimentation and faecal egg sedimentation. There was, however, a disparity between ELISA results and faecal egg flotation results. PMID- 2321351 TI - Different types of inguinal herniation in two stallions and a gelding. AB - Three horses with different and unusual types of inguinal herniation outside the vaginal cavity are described in detail. Attention is paid to the differences between these conditions and the more commonly occurring inguinal herniation inside the vaginal cavity. PMID- 2321352 TI - Postmortal degradation of furazolidone and furaltadone in edible tissues of calves. AB - Rapid and complete postmortal degradation of furazolidone and furaltadone occurred in liver, kidney and muscle tissues of veal calves. Different degradation half-lives were observed between these tissues, the mean ranging from less than 7 minutes to 63 minutes. At 24 h after slaughter the parent nitrofurans were no longer detectable in edible tissues. For residue monitoring purposes plasma and/or urine can be used, if these matrices are treated in a specific way immediately after slaughter; muscle tissues and organs are unsuitable for residue monitoring of parent nitrofurans. PMID- 2321353 TI - O-dealkylation and acetylation of sulphamethomidine by the turtle Pseudemys scripta elegans. AB - The turtle Pseudemys scripta elegans acetylates and O-dealkylates sulphamethomidine. The yield of acetylation (3.1%) is about 0.7 times greater than the yield of O-dealkylation (4.3%). PMID- 2321354 TI - Oral dosage regimen in the nonlinear pharmacokinetics of sulphadimethoxine in pigs. AB - An oral high dosage regimen of sulphadimethoxine (SDM) was examined in pigs. The dose (50 mg/kg) in the therapeutic range, showed nonlinear pharmacokinetics, and administered by drench once a day for 4 days. The unbound plasma concentration time profile was compared with that of the dosage regimen based on nonlinear pharmacokinetics, where a pharmacokinetic model and parameters were used except for the first order absorption rate constant (ka) and bioavailability (F). F and ka were obtained from oral and intravenous administration of 20 and 10 mg/kg of SDM. The unbound plasma concentration was observed almost within the setting range by the dosage regimen through the experimental period. This result suggested that the dosage regimen, based on the nonlinear pharmacokinetic model, resulted in an appropriate effect in the clinical use. PMID- 2321355 TI - Coding of image contrast in central visual pathways of the macaque monkey. AB - Measurements of contrast sensitivity were obtained from isolated neurons in the lateral geniculate nucleus, striate cortex, and middle temporal visual area of macaque monkeys. Between the lateral geniculate nucleus and the middle temporal area contrast sensitivity functions become progressively steeper. Furthermore, many neurons in the middle temporal area are more sensitive than any cell encountered in early stages. Measurements made with stimuli of different sizes show that this high sensitivity depends on areal summation across the receptive field. PMID- 2321356 TI - Cortical acuity and the luminous flux collected by retinal ganglion cells at various eccentricities in human rod and cone vision. AB - Using areally M-scaled, luminance-modulated orange-red and black-and-white gratings, we measured monocular resolution as a function of luminance at various eccentricities in the temporal visual field. In cone vision the increase of grating acuity with luminance became similar at all eccentricities when (1) acuity values were divided by the human cortical magnification factor to express grating resolution in cortical terms (c mm-1) and (2) retinal illuminance was multiplied by Ricco's area to express luminance in terms of photopic luminous flux. The same MF-scaling procedure also applied to scotopic acuity except that the amount of luminous flux collected by retinal ganglion-cell receptive-fields was in rod vision found to increase with eccentricity faster than photopic Ricco's area. PMID- 2321357 TI - Geometric relations of eye position and velocity vectors during saccades. AB - Measurements of angular position and velocity vectors of the eye in three human and three monkey subjects showed that: (1) position vectors lie roughly in a single plane, in accordance with Listing's law, between and during saccades; (2) primary position of the eye is often far from the centre of the oculomotor range. (3) saccades have nearly-fixed rotation axes, which tilt out of Listing's plane in a systematic way depending on current eye position. Findings 1 and 3 show that saccadic control signals accurately reflect the properties of three-dimensional rotations, as predicted by a new quaternion model of the saccadic system; models that approximate rotational kinematics using vectorial addition and integration do not predict these findings. PMID- 2321358 TI - The slope of the psychometric function at different wavelengths. AB - Many current models of visual detection predict that the slope of psychometric functions for detection will be independent of the spectral power distribution of the test light once the spatial and temporal characteristics of the light are fixed. This article examines reports that the slope of the psychometric function depends on the wavelength of a spectrally-narrowband test light of fixed size and duration. Three sources of difficulty that any experimental measurement of slope must encounter are addressed: (1) the different spatial distributions of the photoreceptor classes across the retina; (2) possible variations in threshold over the course of the experiment; and (3) the large variability of estimates of slope and the need for a method of assessing this variability. Measurements of slope with 2 and 4 deg test flashes against a bright 510 nm field show no significant trend with the wavelength of the test. A novel statistical test bounds the magnitude of possible variations in slope across the visible spectrum. PMID- 2321359 TI - New phenomena linking depth and luminance in stereoscopic motion. AB - A novel random-dot stereogram (RDS) was used to study stereoscopic motion. For this RDS stimulus, the direction of luminance motion and the direction of the moving cyclopean pattern can be independently controlled. The perceived cyclopean motion was examined under five different conditions, in which the cyclopean pattern was moving either up or down, the luminant dots were: (1) moving in the cyclopean direction; (2) moving opposite to the cyclopean direction; (3) moving orthogonal to the cyclopean direction, (4) stationary; or (5) dynamic (dots uncorrelated in successive frames). The study showed that luminance direction dominated cyclopean direction and that smooth and coherent cyclopean motion is seen only if luminance motion is present. The results suggest that stereoscopic motion is processed by interactions between separate binocular disparity units and luminance motion units, and not by a single binocular motion system, in which binocular units are tuned to both disparity and direction of motion. PMID- 2321360 TI - Genetic studies of variation in Rayleigh and photometric matches in normal trichromats. AB - The inheritance of Rayleigh match midpoints and photometric matches (551-667 nm) was studied in observers with normal color vision. An analysis was performed to evaluate whether the measured interobserver variations in these two traits were consistent with single gene allelic variation, polygenic variation, or environmental factors. A bipartite 2 deg field and a computerized tracking method were used to obtain Rayleigh matches; a new photometric technique, termed heterochromatic modulation photometry (HMP), was used to obtain photometric matches. Data were collected from 72 nonrelated males to determine distribution characteristics for the normal population. The distributions were analyzed for evidence of multimodality and the results indicated that the distributions for Rayleigh match midpoints and HMP matches obtained in this study were unimodal and symmetrical. Data from 52 observers from 5 families were used to study the transmission of the two traits in pedigrees. Statistical analysis of the pedigree data suggested that the major source of variations for Rayleigh match midpoints and for HMP matches were each due to allelic variation at single gene loci; that is, each may be determined by a single gene. Results were inconclusive as to whether variation in the two traits could be determined by the same gene. PMID- 2321361 TI - The subjective sensitivity to small changes in the contrast of a suprathreshold grating. AB - Small periodic (0.25-40 Hz) changes in the contrast of suprathreshold, spatially sinusoidal (0.8-10.5 c/deg) grating test objects were generated on an oscilloscope screen. It was found that the minimum temporal modulation in spatial contrast which could be detected subjectively was approximately proportional to the mean contrast of the grating during the change, provided that the minimal spatial modulation of the grating was above threshold. The contrast increment threshold was dependent on both the grating spatial frequency and the temporal frequency of the modulation: for any fixed temporal frequency in the range 2-8 Hz it increased approximately linearly with spatial frequency; for fixed spatial frequency the threshold was minimal at temporal frequencies of a few Hz. The relevance of these results to the possible role of fast fluctuations in the control of accommodation response is considered. PMID- 2321362 TI - Luminance contrast and motion detection. AB - Direction discrimination was used to measure the minimum and maximum displacement for the detection of motion (Dmin and Dmax) for abruptly displaced sinewave gratings. This was measured for a range of contrast levels from 2 to 32 times the detection threshold for a range of spatially narrow band stimuli. Performance for Dmin (but not Dmax) was found to deteriorate with an increase in contrast, with the most sensitive values for Dmin obtained at contrast levels of 4-8 times detection threshold. This dependence on luminance contrast is thought to be due to the physiology of the visual system, rather than the physics of the stimulus. PMID- 2321363 TI - The interocular luminance yoke: a vestige of phototaxis? PMID- 2321364 TI - Refractive state, ocular anatomy, and accommodative range of the sea otter (Enhydra lutris). AB - Sea otters are carnivorous, amphibious mammals that are active both above and under water. Accordingly, it might be expected that their eyes are adapted for both aerial and aqueous vision. We examined the anatomy and physiological optics of the sea otter eye with a view towards describing and explaining its amphibious visual characteristics. We employed photokeratoscopy to measure the refractive power of the sea otter cornea, which we found to be 59 D. Using video dynamic photorefraction, we found that sea otters can focus targets clearly both in air and water, relying on accommodation to compensate for the refractive loss of their corneas upon immersion in water. Our anatomical investigations revealed that the anterior epithelium of the cornea is extensively developed, as is the iris musculature, meridional ciliary muscle, and the corneoscleral venous plexus. The first feature is most likely an adaptation to the salinity of the marine environment. We believe the latter features are part of a novel, well-developed lenticular accommodative mechanism. PMID- 2321365 TI - Theory and measurement of ocular chromatic aberration. AB - We have determined the transverse chromatic aberration of the human eye by measuring the apparent offset of a two-color vernier viewed foveally through a displaced, pinhole aperture. For the same subjects, we also determined the longitudinal chromatic aberration for foveal viewing by the method of best focus. In both cases, the results were closely predicted by a simple, reduced-eye optical-model for which transverse and longitudinal chromatic aberration are directly proportional, with the constant of proportionally being the amount of displacement of the pinhole from the visual axis. Further measurements revealed that the natural pupil was closely centered on the visual axis for two subjects and slightly displaced in the temporal direction for three other subjects. One implication of these results is that, although the eye has substantial chromatic aberration, the pupil is positioned so as to minimize the transverse component of the aberration for central vision, thereby optimizing foveal image quality for polychromatic objects. PMID- 2321366 TI - Models of the normal and abnormal rod system. AB - A framework is presented for using threshold data to test hypotheses about the action of a disease, a chemical agent, or a developmental process. A model of the normal rod system, based on models from the physiological and psychophysical literature, is presented. Hypotheses about the alteration of the rod system are specified in this model. The approach is illustrated with a class of hypotheses that places the decrease in sensitivity with retinal disease at the rod receptors and with data from patients with retinitis pigmentosa and congenital stationary night blindness. The implications for models of the normal rod system are considered. PMID- 2321367 TI - Real world occlusion constraints and binocular rivalry. AB - A surface occluding a more distant surface gives rise to interocularly unpaired regions to its immediate left and right. The unpaired region on the left side is visible only to the left eye, whereas that on the right side is visible only to the right eye. Thus for real world scenes there are opto-geometrical constraints which determine whether particular combinations of relative depth and right-eye only or left-eye-only stimuli are ecologically valid or invalid. We report a demonstration and experiments to show that opto-geometrically "valid" unpaired regions are seen as continuous with the rear plane and escape interocular suppression, whereas "invalid" unpaired regions are perceived as closer and are suppressed vigorously. An additional experiment indicates that the results cannot be understood in terms of correspondence solving, but require neural mechanisms that embody real-world occlusion constraints. These results suggest a rather close interaction between stereopsis and rivalry "modules". Since explicit eye-of origin information is lost relatively early in the hierarchical organization of cortical visual processing, we argue that occlusion-related constraints must be embodied at such early levels. PMID- 2321368 TI - Spatial sensitization in the short wavelength sensitive pathways under dichoptic viewing conditions. AB - Spatial sensitization (Westheimer) functions were measured under conditions that isolated the short wavelength sensitive pathways. The variable diameter pedestal and the test probe were either presented to the same eye (monoptic presentation) or to different eyes (dichoptic presentation). The most significant new finding was that a dichoptically presented, small, blue pedestal caused threshold elevations of about 1-2 long units for an S cone detected probe. However, a large pedestal caused little or no change in threshold. This result contrasts with previous results using white light stimuli, which showed that steadily presented dichoptic pedestals caused little or no threshold change. Furthermore, we show there is little masking when the probe is detected by the isolated M or L cone pathways. These data thus demonstrate a binocular, size dependent interaction revealed only when S cones detect the probe. PMID- 2321369 TI - Computing three-dimensional eye position quaternions and eye velocity from search coil signals. AB - The four-component rotational operators called quaternions, which represent eye rotations in terms of their axes and angles, have several advantages over other representations of eye position (such as Fick coordinates): they provide easy computations, symmetry, a simple form for Listing's law, and useful three dimensional plots of eye movements. In this paper we present algorithms for computing eye position quaternions and eye angular velocity (not the derivative of position in three dimensions) from two search coils (not necessarily orthogonal) on one eye in two or three magnetic fields, and for locating primary position using quaternions. We show how differentiation of eye position signals yields poor estimates of all three components of eye velocity. PMID- 2321371 TI - Predicting paternal role enactment. PMID- 2321370 TI - The fattening room revisited. PMID- 2321373 TI - Diagnosing and dealing with multicollinearity. AB - The purpose of this article was to increase nurse researchers' awareness of the effects of collinear data in developing theoretical models for nursing practice. Collinear data distort the true value of the estimates generated from ordinary least-squares analysis. Theoretical models developed to provide the underpinnings of nursing practice need not be abandoned, however, because they fail to produce consistent estimates over repeated applications. It is also important to realize that multicollinearity is a data problem, not a problem associated with misspecification of a theorectical model. An investigator must first be aware of the problem, and then it is possible to develop an educated solution based on the degree of multicollinearity, theoretical considerations, and sources of error associated with alternative, biased, least-square regression techniques. Decisions based on theoretical and statistical considerations will further the development of theory-based nursing practice. PMID- 2321372 TI - Family routines and conduct disorders in adolescent girls. PMID- 2321374 TI - Development of the family needs assessment tool. PMID- 2321376 TI - Inhibitors and facilitators to documentation of nursing practice. PMID- 2321375 TI - A grounded theory study of the informed consent process for pharmacologic research. PMID- 2321377 TI - Hermeneutical inquiry. Meaning and scope. PMID- 2321378 TI - Time-series analysis. Use of autocorrelation as an analytic strategy for describing pattern and change. AB - Although graphic representation of time-series data is one method to describe patterns of phenomena, autocorrelations, correlograms, and plots of the autocorrelation function provide descriptive and statistical methods that reveal the structure of a deterministic cycle component within the time-series. The autocorrelation function provides a method for the investigator to test hypotheses about the nature and pattern of relationships between measured and latent variables. Patterns of phenomena can be analyzed statistically using objectively provided criteria. The autocorrelation function can also be used to understand the change in response or behavioral patterns following an experimental intervention. Traditional group comparison designs, using cross sectional data collection strategies cannot identify differences within the individual nor can they identify patterns of behavior or structural patterns within the data. Autocorrelation and cross-correlation become threats to statistical validity when conventional methods are used; however, in time-series analysis, autocorrelation allows close scrutiny of the pattern of response within an individual across a time-dimension. PMID- 2321379 TI - Student-staff collaboration in identifying nursing problems and reviewing the literature. PMID- 2321380 TI - [Double photon absorptiometry in renal osteodystrophy]. AB - Bone mineral content (BMC) of the lumbar spine (L2-L4), femoral neck, Ward's triangle and the trochanteric region was measured in 52 consecutive patients on maintenance haemodialysis. In the whole group the median BMC value as percentage of sex- and age-matched normal means was significantly decreased only in Ward's triangle (91.7%; p less than 0.02). In patients with chronic interstitial nephritis there was a significant decrease in bone density in Ward's triangle and the trochanteric region (p less than 0.02). There was no correlation between BMC and time on dialysis or intact parathormone. BMC value did not predict the type of renal osteodystrophy, according to Delling. 17 patients underwent a second investigation after one year. There was a slight fall in mean BMC of the lumbar spine (-0.9%) and Ward's triangle (-1.1%). The fall in mean BMC of the trochanteric region was pronounced (-3.2%). We believe that the observed low demineralisation, which was more pronounced in patients with interstitial nephritis, may be attributable to early and carefully monitored therapy with vitamin D metabolites. PMID- 2321381 TI - ["Membrane attack complex" formation in hemodialysis treatment]. AB - The behaviour of plasma concentrations of the membrane attack complex (MAC) during haemodialysis was studied in 23 patients. An increase in the levels up to 250% of the initial value was noted when Hemophan or Cuprophan membranes were used. Patients dialyzed, with Polysulfon membranes showed only a slight increase in MAC levels. In the Hemophan and Cuprophan group a plateau developed lasting from 15 to 120 minutes after onset of the haemodialysis session. The MAC may serve as marker of biocompatibility. Furthermore, it seems to be involved in many untoward effects of haemodialysis treatment. PMID- 2321382 TI - [Experiences and clinical results following 99 kidney transplantations with kidneys from relatives]. AB - 99 living related kidney transplantations were performed between January 1967 and December 1988. At the time of observation 4 of 94 organ donors had died; there was no correlation between unilateral nephrectomy and the patient's death. Intraoperative (2.9%) and postoperative (25%) complications did not result in severe physical consequences for the organ donors. Hypertension was found in 2 donors. There was no decrease in function of the remaining kidneys. The 3-year organ survival of the transplanted kidney was 60% with "conventional immunosuppression" and 93% with cyclosporin. No association was found between HLA DR-matching and graft survival. Rejection episodes occurred significantly more often in the HLA DR-mismatched grafts. PMID- 2321383 TI - [European Fructosamine Workshop. Vienna, 26-28 October 1989. Proceedings]. PMID- 2321385 TI - [Determination of fructosamine in chronic kidney diseases (dialysis-dependent patients)]. AB - The serum fructosamine normal range was confirmed. Correction to protein or albumin did not significantly affect the results. Therefore, correction of fructosamine values from patients with normal protein and albumin values would not improve the clinical significance of fructosamine. Fructosamine concentrations of heparin plasma from non-diabetics also fell within the serum fructosamine normal range. The fructosamine concentration from non-diabetic dialysis patients was significantly higher and more widely distributed than that of the reference collective despite normal blood glucose concentration. Relating fructosamine to protein had no substantial effect, whereas the differences were even increased when fructosamine was related to albumin. On the present stage of knowledge it might be considered to establish a reference interval for dialysis patients. It appears that the fructosamine estimation may then be successfully applied also to dialysis patients. Although dialysis resulted in hemoconcentration, the fructosamine concentration remained virtually unchanged. Referencing both values before and after dialysis to protein or albumin improved the correlation, but substantial differences were introduced as well. However, none of several parameters measured in parallel interfered to a degree which might explain such differences. In order to find a reasonable explanation for these findings further experiments are necessary. PMID- 2321384 TI - [The value of fructosamine in hemodialysis patients]. AB - Fructosamine is thought to be an alternative diabetic long term parameter to HbAlc. A possible advantage of fructosamine is the shorter half life of this parameter. Therefore changes in the metabolic control of diabetes can be evaluated faster. However, daily variations of protein concentrations limit the clinical usefulness of fructosamine, especially in patients on hemodialysis, where we see variations in total protein- and albumin concentration during dialysis. Due to these limitations we studied the clinical usefulness of a new fructosamine assay in 38 patients with chronic renal failure. Fructosamine values, total protein, albumin, blood glucose and creatinine were measured before and after three hours hemodialysis treatment as well as glycosylated hemoglobin. Before dialysis HbA1c correlated with HbA1c after dialysis (r = 0.99), which documents the usefulness of glycosylated hemoglobin in patients on hemodialysis. Fructosamine before dialysis shows a correlation with fructosamine values after dialysis of r = 0.77. After correction with total protein the correlation was r = 0.95, also after correction with albumin. Fructosamine values before and after dialysis correlated excellently (r = 0.95). Fructosamine values before and after dialysis can only be compared after correction with total protein or with albumin. PMID- 2321386 TI - [Fructosamine values in hyperthyroidism, hypothyroidism and gammopathy]. AB - Fructosamine values in two groups of hypo- and hyperthyroid patients were compared with the values in a reference group of non-diabetics. In hyperthyroid patients the fructosamine values were significantly lower than in the reference group. Also the mean concentrations of albumin and total protein in serum are significantly lower for hyperthyroid patients compared to hypothyroid patients. The results do not provide evidence for a simple relationship between fructosamine and protein values in these patient groups. Therefore we do not recommend to relate fructosamine to protein or albumin using correction factors. Under conditions of thyrotoxicosis fructosamine is no reliable indicator of previous serum glucose concentrations. The test is not affected by monoclonal IgG gammopathy. PMID- 2321387 TI - [The effect of hyperlipoproteinemia on serum fructosamine]. AB - In 127 patients, we investigated the influence of hyperlipemia on observed fructosamine values. An in vitro influence of the lipids on the fructosamine reading could be excluded for cholesterol, HDL-cholesterol and triglycerides. However, in patients with type I diabetes, both, cholesterol and triglycerides significantly (p less than 0.05) correlated with fructosamine. This may be explained by in vivo effects of hyperglycemia on lipids or lipoproteins. For a given level of hyperglycemia, fructosamine is slightly more sensitive than HbA1c. PMID- 2321388 TI - [Venous stasis and orthostasis as factors influencing fructosamine concentration]. AB - The concentrations of high molecular weight blood constituents are influenced by the increased intravascular pressure at sample collection. The impact on the fructosamine concentration was compared with that on total protein, plasma protein, electrolytes, and protein bound analytes such as calcium. The results show that fructosamine concentration behaves similar to that of total protein and albumin with change in resting position and venous-stasis. PMID- 2321389 TI - [Fructosamine values in venous and capillary blood]. AB - The determination of fructosamine could also be performed in serum obtained from capillary blood. The sample taking using micro sample carriers for capillary blood is more convenient for the patients. The described procedure is an alternative way suitable for the determination of fructosamine in ambulance and in doctor's office. Results obtained with uncoated micro carriers and capillary blood are in good agreement with fructosamine values from venous blood. However, the use of sample carriers coated with EDTA or heparin produced discrepant results. PMID- 2321390 TI - [The effect of orthostasis on the fructosamine value]. AB - With the introduction of an improved method for the determination of fructosamine a new tool is available for the monitoring of diabetes. This method provides a good reproducibility together with a standardized quality control and is easily applicated to automated clinical chemistry analyzers. Besides the analytical performance in general the impact of preanalysis on fructosamine values is important for routine work. In a study with 20 volunteers the impact of orthostasis has been investigated. Changes in fructosamine concentration correspond to a shift in the concentration of other analytical parameters related to serum proteins. PMID- 2321391 TI - [New formation of fructosamine in patient serum following blood collection]. AB - The stability of fructosamine has been analysed in sera of 24 patients. Fructosamine concentrations increased daily with a constant rate of formation. Synthesis of fructosamine in vitro strongly depended on the incubation temperature and was directly proportional to the glucose concentration of the sample. It is recommended to store sera for the determination of fructosamine at 4 degrees C or - 20 degrees C. PMID- 2321393 TI - [Age dependence, sex independence and reference values of serum fructosamine determined using a new colorimetry method]. AB - Reference ranges were evaluated for a new colorimetric method for the determination of fructosamine in serum. The reference group was composed of 1114 non-diabetics of both sexes including children. Reference values are only slightly affected by age and sex. In the course of childhood to adolescence fructosamine values raise and finally stabilize in adults. The small differences between both sexes have no effect on the interpretation of clinical results. Relating fructosamine values to albumin or total protein has little impact on the distribution of the values when protein values were within the reference range. PMID- 2321392 TI - [Effect of a change in posture on the diurnal variations of fructosamine concentration in diabetic patients]. AB - Daily profiles of blood glucose, HbA1c, total protein and fructosamine were measured in 10 diabetic patients and the factor fructosamine x 7/g total protein was calculated. Measurements were done at 4 a.m. to be sure that the patients were sleeping for some time, during the day and the following evening at 11 p.m., when the patients were lying again, so that the influence of orthostasis, the difference between bed rest and walking could be demonstrated. The blood glucose profile was typical whereas the HbA1c concentration was very stable and constant. Total protein and fructosamine increased significantly by orthostasis; the correction of fructosamine by total protein diminished the differences, but did not completely eliminate the effect of orthostasis. However, fructosamine should be corrected by the total protein concentration in order to increase the diagnostic value of the parameter. PMID- 2321394 TI - [Fructosamine reference ranges for pregnant patients and children determined using an improved NBT method]. AB - Reference values for fructosamine in pregnancy show a decrease with progressing pregnancy, which can be explained by pregnancy-associated hemodilution. A normalization to 7.0 g/dl total protein leads to values independent of gestational age. For children and adolescents age-dependency of the reference range is abolished if values are related to total protein. More plausible values are obtained in longitudinal profiles if fluctuations of protein concentration are taken into account. PMID- 2321395 TI - Performance and clinical significance of the new fructosamine assay in diabetic patients. AB - The performance of the assay and the clinical usefulness of a new short-term index (Fructosamine Plus: FP) of metabolic control in diabetes was evaluated. The FP concentration was determined with the Hitachi 704, Cobas Mira, and Cobas Fara analyzers. The "within run" and "between run" CVs were less than 2.67% and less than 4.26%, respectively. The reference interval (determined from data on 125 blood donors) was 191 to 288 mumol/l (mean 240 mumol/l). In poorly controlled diabetic patients FP was significantly higher than in the well controlled ones. Moreover FP was significantly correlated with HbA1c and blood glucose levels. Our preliminary data seem to demonstrate that relating FP to total protein does not improve the clinical value of the new index. PMID- 2321396 TI - [Diagnosis of the diabetic metabolic status using fructosamine (and HbA1c) determination. The glycation quotient Glyc-Q, the glycation nomogram]. AB - The determination of fructosamine in serum is an accepted tool for the metabolic monitoring of diabetic patients. It provides an estimation of the glycemia state during the preceding 10 to 20 days. The turn-over of serum proteins is in general faster than that of hemoglobin. Therefore, fructosamine is faster responding than HbA1c to recompensation or fluctuations in glycemic control as observed in labile metabolic situations. On the other hand, under conditions of stable metabolic control fructosamine values correlate closely to HbA1c. The relation between the two parameters can be visualized in a nomogram of HbA1c, fructosamine and glucose or be expressed by a quotient (Glyc-Q = Fructosamine*2.2/HbA1c). A deviation from the stable metabolic situation (Glyc-Q = 100) reflects a trend in the recent development of glycemia: a Glyc-Q of greater than 120 is obtained in the state of decompensation, whereas in recompensation the Glyc-Q decreases significantly to values below 80. We propose to use the Glyc-Q in situations where a fast assessment of the glycemic state or an estimation of the development of glycemia within short intervals of observation are required. PMID- 2321397 TI - [Fructosamine as a parameter for monitoring carbohydrate metabolism in the treatment of diabetes mellitus]. AB - Fructosamine, protein, albumin and HbA1c from 199 diabetics were followed for up to 220 days. An increase in average blood glucose during the preceding 10 days causes an increase in fructosamine by 50 mumol/l. During the day there is little variation in the fructosamine concentration, whereas relating fructosamine to protein or albumin results in substantial fluctuations. A possible cause is the necessity for two measurements which is associated with an increased error. Long term observations reveal a significant correlation between fructosamine and HbA1c which is little affected by relating fructosamine to protein or albumin. Diabetics exhibited significantly lower protein and albumin concentrations than the normal collective, yet the standard deviations from the individual means were only 7 and 7.9%, respectively. PMID- 2321398 TI - [Diurnal variations of fructosamine in patients with type II diabetes mellitus]. AB - During the last years fructosamine has been presented as a measurement of diabetic long term control, particularly a shorter half life of fructosamine was seen as an advantage over HbAlc (half life of fructosamine: 16 days, half life of HbAlc: 28 days). Due to diurnal variations of fructosamine levels especially in dependence of variations of the albumin-and protein concentrations the interpretation of this parameter was somewhat limited. Recently a new colorimetric fructosamine-assay was developed. We investigated the diurnal variations of fructosamine in 28 patients with type II diabetes. Fructosamine, glucose, albumin, total protein and creatinine were measured at the times towards 3, 6, 9, 12 a.m. and 3, 6, 9, and 12 p.m. In relation to the 6 a.m. fructosamine value (= 100%) the fructosamine levels showed a daily variation from -4% at 3 a.m. to +11% at 9 a.m. Correcting fructosamine levels with total protein or with albumin reduced the variations to -1% to +6% or -3% to +9%. Daily profiles of the new fructosamine assay show a daily variation which can be minimized by correcting with protein-or with albumin concentrations. For clinical routine the daily variations especially of the corrected fructosamine levels are neglectible. PMID- 2321399 TI - [Fructosamine as a diagnostic parameter in the clinical routine]. AB - The fructosamine normal range was established from a collective of 90 healthy individuals as 219-285 mumol/l (+/- 2s; mean 240 mumol/l). From a group of 10 diabetics day profiles of glucose, protein, albumin, and fructosamine were recorded by measuring these parameters three times per day at 8.00, 11.30, and 15.00. The fructosamine concentration was essentially constant also when related to protein or albumin. Fructosamine, HbAlc, CK, and CK-MB were determined from 12 diabetics with fresh myocard infarct (7 diabetics, 5 non-diabetics). Surprisingly, diabetics as well as non-diabetics manifested high fructosamine concentrations. The origin of the fructosamine increase with non-diabetic myocard infarct patients is not yet known. Possibly the acute metabolic disorder plays an important role. An influence of fibrinogen on fructosamine is also conceivable. Additional investigations, including therapy of lysis, will be carried on. The stability of the fructosamine was examined by storing 50 sera (fructosamine 295 491 mumol/l, glucose 180-279 mg/dl) at different temperatures (+ 25 degrees C, + 4 degrees C, - 20 degrees C). At - 20 degrees C and + 4 degrees C fructosamine increases by up to 2% in 24 hours. At + 25 degrees C a 6% increase in fructosamine was observed within the same observation period. PMID- 2321400 TI - [Changes in the plasma protein concentration as a factor influencing the fructosamine value]. AB - Fructosamine values are notably influenced by plasma protein concentration. Total protein concentration in addition to variations in the plasma protein concentrations (Dysproteinemia) play a role here. This is a result of the various glycosylation of the different plasma proteins. Since fructosamine behaves similar to total protein for hypo- and hyperproteinemia, a good relationship with the total protein is expected for normoproteinemia. Hence, no erroneous high nor low fructosamine values are obtained. Dysproteinemia at normal total protein concentration causes no erroneous fructosamine values with the exception of some illnesses. Therefore, a direct relationship between protein and fructosamine at normoproteinemia is not generally necessary. PMID- 2321401 TI - [Albumin or protein standardized fructosamine-plus, 2 new indices for evaluating diabetic metabolic status]. AB - We have evaluated a new method for the determination of glycated serum proteins (fructosamines), which are elevated in diabetics. In accordance with earlier findings fructosamine depends not only on mean blood glucose but also on albumin- and total protein concentrations. Therefore fructosamine is not useful as an index of diabetic blood glucose control without consideration of an individuals albumin- or protein-concentration. We propose albumin- or protein-standardized fructosamines as new indices of diabetic control. PMID- 2321402 TI - [The limits of fructosamine determination]. PMID- 2321403 TI - Wisconsin's Clean Indoor Air Act. PMID- 2321404 TI - Cocaine use during pregnancy: implications for physicians. AB - The growing use of cocaine among pregnant women and its effect on the fetus have become issues of great concern to physicians and society in general. In this paper, we review the available data about the incidence of cocaine use during pregnancy in the United States and in Wisconsin. The pharmacology of the drug is examined as well as its effect on pregnancy outcomes. Medical, neurobehavioral, and developmental effects on the fetus, newborn, and infant are discussed, as well as the relationship to the timing of drug use during pregnancy. Suggestions relevant to physicians for prevention and treatment are given. PMID- 2321405 TI - Perinatal follow through: implications for primary physicians. AB - Neonatal intensive care unit follow-through programs provide early evaluation information for the primary care physician. This article describes such data for 339 graduates of St Joseph's Special Care Nursery, 78% of whom were preterm and 70% were of low birth weight. At six months, 7% of the infants were diagnosed with cerebral palsy, based on a 15-month follow-up. Other neurological and respiratory problems were common. A normal neurodevelopmental outcome was found for the majority of the infants. Referrals to medical specialists (eg, ophthalmology) and early intervention programs were required for many infants. The case management role of the primary physician is highlighted along with specific recommendations for care of the medically at-risk or developmentally delayed infant. PMID- 2321406 TI - Surveillance of environmental disease: the Wisconsin initiative. PMID- 2321407 TI - A rare cause of small bowel perforation by intestinal and peritoneal tuberculosis. AB - Tuberculosis of the intestine and peritoneum has become a rare disease. This is the result of a general decrease in pulmonary and extrapulmonary tuberculosis, rigorous BCG vaccination programs, and the eradication of tuberculosis in cattle. A case of tuberculosis in this frequent location, which was discovered unexpectedly during an emergency laparotomy, is reportet. PMID- 2321408 TI - [Massive hemorrhage from an "esophageal tumor": thoracic aortic aneurysm rupturing into the esophagus]. AB - We report on an arteriosclerotic aneurysm of the descending aorta penetrating into the esophagus. On endoscopy it mimicked a bleeding esophageal tumour. The typical clinical course of aortoesophageal fistulas (AEF) exhibits Chiari's triad of midthoracic pain, sentinel arterial hemorrhage, usually hematomesis, and final exsanguination after a symptom-free interval. The various causes of AEF are discussed together with the respective diagnostic and therapeutic problems. PMID- 2321409 TI - [Treatment of chronic calcified pancreatitis by extracorporeal shockwave lithotripsy?]. PMID- 2321410 TI - [The "depressed adenoma" of the stomach]. AB - Depressed adenoma of the stomach, whose gross appearance is similar to that of type IIc early gastric carcinoma, was detected in 40/357, or 11%, of gastric resection preparations. Depressed adenoma is primarily found in the two distal thirds and the lesser curvature of the stomach. It presents as a flat brownish depression and measures between 2 and 39 mm across (mean 13 mm). Histology typically reveals tubular adenoma with closely spaced atypical columnar epithelial cells of the intestinal type. Depressed adenoma probably arises from pre-existing depressed lesions (erosions, ulcer scars, atrophic zones) rather than from conventional protuberant adenoma. Depressed adenoma appears to show a greater tendency for malignant differentiation than do conventional adenomas. PMID- 2321411 TI - [Validation of trend-supported ST segment analysis of long-term ECG recordings]. AB - Trend recordings of relative ST-segment deviations represent a useful tool for the identification of ischemia-like episodes during Holter monitoring. For the generation of trend recordings beat-to-beat data are filtered. The influence of the time constant of the filter on the sensitivity and the specificity for the detection of ischemia-like ECG changes is unknown, however. Ischemia-like episodes were, therefore, simulated and recorded by a frequency modulated Holter recorder and by a conventional six-channel ECG system. Relative ST-segment deviations were filtered using a time constant of 8, 16, 32 or 64 s, or an arithmetic averaging over 9 s for the generation of ST-segment trends. The magnitude of short-lasting ST-segment deviations was underestimated, when beat-to beat data were filtered using time constants of greater than or equal to 32 s. The influence of posture-related ECG changes on the ST-segment trends was investigated by recording lead CM5 in 14 consecutive patients in different positions by a conventional ECG system. Four out of the 14 patients developed ST segment elevations greater than or equal to 0.1 mV during leftsided position. Only in these four patients were ST-segment deviations of similar magnitude recorded during the following Holter monitoring. The posture-related ST-segment changes were characterized by an abrupt onset and an abrupt end, resulting in a box-like shape which enabled their correct identification in the ST-segment trend analysis. In order to determine the relative frequency of posture-related ST segment changes, 35 patients with coronary artery disease (CAD) and 35 patients without underwent Holter monitoring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321412 TI - [Abstracts of the autumn meeting of Austrian Cardiology Society. Graz, 29-30 September 1989]. PMID- 2321413 TI - [Accuracy of various Doppler technics in recording blood flow velocity. Studies in vitro]. AB - Conventional and color-coded Doppler techniques were studied as to their accuracy in displaying flow and velocity using an in vitro model and a Laser-Doppler anemometer. Furthermore, the estimation of pressure gradients as determined by Doppler ultrasound was compared to measurements by manometers under a variety of hemodynamic conditions. Pulsed and continuous wave Doppler had good reproducibility. There was an excellent correlation for measurements of flow velocity as determined by Doppler ultrasound and by Laser-Doppler anemometer (r = 0.98, SEE = 3 cm/s). The well-known underestimation of flow velocity due to an increasing angle of incidence (greater than 25 degrees) was confirmed in vitro. However this error was smaller than the actual overestimation resulting from angle correction for the apparent cosine. Doppler gradients correlated strongly with manometer gradients for orifice areas 12-80 mm2 and flow volumes 0.9-12.8 l/min (r = 0.98, SEE = 7 mm Hg) using continuous as well as pulsatile flow. Some overestimation of the Doppler gradient occurred with increasing flow rates (r = 0.66). Color-Doppler has poor spatial resolution. Display of velocities was therefore assessed using a qualitative score (0-5), the variability of which was 13 +/- 30% of the initial value. Display of faintest quality (score 1) was useless for clinical assessment in color-Doppler technique, but allowed quantitative measurement of velocity in conventional Doppler. Reduction of flow velocities limited display in color-Doppler (5-20 cm/s) but not in pulsed-Doppler technique. Thus, conventional Doppler has better sensitivity and accuracy of displaying flow when compared to color-Doppler, particularly in conditions of poor imaging. As reproducibility and accuracy of velocity determination are excellent, this technique should be used in all diagnostic procedures involving ultrasound. The Doppler gradient as derived from the modified Bernoulli equation provides accurate results in vitro which may also be concluded for use in the clinical situation. PMID- 2321414 TI - [Cardiac involvement within the scope of HIV-1 infection: preliminary results of echocardiography study]. AB - The results of one- and two-dimensional echocardiography in 128 patients (117 males, 11 females; median age 37 years) who were seropositive for HIV-1 were analyzed in addition to clinical, electrocardiographic, and laboratory data. Follow-up controls are available for 51 patients over an observation period of 1 to 24 months, median 9.5 months. Probably HIV-related echocardiographic abnormalities were identified in 36 patients (28%): small to moderate pericardial effusions (n = 34) and left ventricular dilation (n = 5). Pericardial effusions resolved in seven patients during follow-up, in three cases after tuberculostatic chemotherapy. Compared to patients without cardiac involvement patients with HIV related echocardiographic abnormalities showed lower CD4-lymphocyte counts (143 +/- 138 vs 289 +/- 219/microliters, p less than or equal to 0.01), and left ventricular endsystolic dimensions were increased (34.2 +/- 4.5 vs 32.6 +/- 3.0 mm, p less than or equal to 0.05). Cardiac involvement occurred predominantly in the advanced stages of the HIV-1 infection with unclear etiology in the majority of cases, even though active concomitant diseases could be frequently demonstrated. The clinical course of some patients might be consistent with intercurrently completed perimyocarditis, probably of viral genesis. CD4 lymphocyte counts less than or equal to 100/microliters could be identified as a risk factor for the development of cardiac manifestations. The significance of a demonstrated involvement of the heart with regard to therapeutic consequences and prognosis appeared to be slight. Use of echocardiography as a routine method for the detection of cardiac involvement in HIV-1 infection has proved to be valuable, since indicative clinical symptoms were lacking in almost all cases. PMID- 2321415 TI - [Interobserver and spontaneous variability of Doppler echocardiography measured cardiac output in children with congenital heart defects]. AB - Doppler-derived cardiac output (CO) measurements were performed on 2 consecutive days in 30 children with surgically corrected congenital heart diseases. The children formed three subgroups of 10 patients each according to age (group 1 = less than 1 year, 2 = 1-5 years, 3 = greater than 5 years). Pulsed Doppler recordings were carried out over pulmonary and aortic valves using standard projections. All recordings were "blindly" evaluated by two independent investigators. In each age group day-to-day and interobserver variability were assessed for CO, cross-sectional area of the vessel (A), time-velocity integral (I), and heart rate (HR). Day-to-day variability for CO ranged between 20% and 33% depending on age and sampling site. The corresponding variabilities for A, I, and HR were 19-35%, 14-23%, and 9-11%, respectively. Spontaneous variability did not differ significantly between the three age groups. Interobserver variabilities for CO, I, A, and HR were 13-40%, 14-32%, 20-55%, and 1-3%, respectively. A of the aorta in group 1 and aortic I in group 3 were significantly different (p less than 0.05) for both observers. None of the remaining parameters, measured by both observers, were significantly different. CO and I revealed a higher interobserver variability (p less than 0.01) for infants (group 1) than for older children, when determined over the pulmonary valve. In addition, interobserver variability of aortic cross-sectional area was significantly increased (p less than 0.01) for the young age group (group 1). We conclude that there is a considerable spontaneous and interobserver variability of Doppler-derived CO measurements in pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321416 TI - [Fetal echocardiography and clinical genetics--a close correlation]. AB - Improving techniques in fetal echocardiography have important implications in the field of clinical genetics. 1) Fetal echocardiography in pregnancies with families with increased recurrence risks for congenital heart disease (CHD): In 473 pregnancies with increased recurrence risks for CHD second-trimester fetal echocardiography was performed. In 11 cases (2.3%) cardiac malformations were present that could be diagnosed in five cases prenatally (hypoplastic left heart, complete atrioventricular canal defect with hypoplastic left ventricle, preductal coarctation of aorta, tetralogy of Fallot, complete atrioventricular canal defect). In six cases the prenatal diagnosis could not be performed (total anomalous pulmonary venous connection [one case], secundum atrial septal defect [two cases], ventricular septal defect [three cases]). The recurrence risk in families with one previously affected child was 1.4% (5/364), and 17.6% (3/17) in families with two previously affected children. In two out of 44 cases with one affected parent a CHD could be diagnosed, in both cases one previous child was already affected. 2) Congenital heart defect as a common symptom in malformation syndromes: CHD is common as a symptom in malformation syndromes. The demonstration of a fetal CHD can lead to diagnosis of a complex malformation syndrome and it is integral in prenatal diagnosis in cases with increased recurrence risks for a complex malformation syndrome. The sonographic diagnosis of a CHD may signal associated chromosomal disorders. Between January 1986 and December 1988 in 433 cases with prenatally diagnosed congenital malformation and/or severe fetal growth retardation a prenatal chromosome analysis was performed. Within this group 77 fetuses demonstrated a CHD and 28 (36%) out of these revealed a chromosomal disorder. The genetic basis of CHD, the most common complex syndromes with CHD, and the principles of genetic counseling in families with CHD are summarized. PMID- 2321417 TI - Mature, cell-associated HN protein of Newcastle disease virus exists in two forms differentiated by posttranslational modifications. AB - Characterization of the posttranslational modifications of the mature, cell associated hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) revealed that the HN protein exists in two forms differentiated by disulfide bonds and glycosylation. One form, HNa, contains intermolecular disulfide bonds and is endoglycosidase H partially resistant. The other form, HNb, is not linked by disulfide bonds and is endoglycosidase H sensitive. Both forms of the protein are modified with fucose indicating transport to the Golgi membranes. Both forms are detected at the cell surface by monoclonal antibody. Furthermore, both forms are transported to the cell surface with identical kinetics. HNa is incorporated into virions. HNb is not incorporated into virions and is presumably degraded. The cDNA derived from the HN gene was expressed from a retrovirus vector. The majority of the protein expressed was in the nonvirion associated form b. Evidence is presented that the level of gene expression determines the ratio of the two forms of HN protein. At high levels of expression, the virion-associated form is favored while at low levels of expression the nonvirion-associated form is favored. The results presented have implications for persistent infections as well as expression of viral genes from different vectors. PMID- 2321418 TI - [Papers presented at the 26th annual meeting of the German Association of Pediatric Surgery. Mainz, 8-10 September 1988]. PMID- 2321419 TI - [Possibilities for assessing unilateral functional disorders of the upper urinary tract in infants with urethral valves]. AB - Upper urinary tract function was evaluated in 15 infants in whom urethral valves were diagnosed. One baby died at 16 days of age and was not completely investigated. In 4, the valves did not have untoward effect on the bladder and the upper urinary tract. In 10 others, function was evaluated using the Hodson index, creatinine, PAH, inuline clearance and renal I123-Hippuran scintigraphy with measurement of the accumulation indices. The various examination procedures were of value in providing precise evaluation of the renal performances at diagnosis as well as in prognosis and follow-up of the function of each kidney. PMID- 2321420 TI - [Treatment of urethral valves with and without valve resection in the 1st year of life]. AB - 25 infants of a total of 72 child patients, who were treated between 1967 and 1987 in the Department of Paediatric Surgery of the Paediatric Hospital of the City of Cologne and were suffering from congenital urethral valves, had been transferred to the hospital for in-patient treatment within their first year of life. In accordance with a change in the treatment concept the patient material was divided into two groups: 1. Treated children up to 1978 These patients were subjected to a prolonged transurethral bouginage treatment of the urethra. Valve resection was performed subsequently at an average age of 13 months only. 2. Treated children after 1978 In these children valve resection was performed as soon as possible after birth. These two patient groups were compared with each other. It was found that both the survival times and the long-term renal function results of the children treated after 1978 had markedly improved compared with those treated before 1978, thanks to the modern treatment concept. That is true both for the incidence of secondary correction operations at the upper part of the urinary tract and for the frequency of nephrectomy. PMID- 2321421 TI - [Diagnosis, therapy and follow-up of infants with urethral valves, treatment concept in the 1st year of life]. AB - Within the framework of a joint follow-up we report on the treatment of 57 infants with urethral valves (35 babies from Munich and 22 from Siegen) in the first year of life, studied between 1974 and 1986. In 16 newborn the diagnosis and initiation of treatment was effected during the first four weeks of life (Group I) and in 41 babies during the 2nd to 12th month (Group II). In three cases, diagnosis of suspected urethral valve was made prenatally. Primary management and the concept of further treatment are described. Primary therapy is determined by the general condition after birth, presence of urosepsis and the extent of any existing renal insufficiency. 2 children died, both from Risk Group I. 5 children are in a state of compensated renal insufficiency. In 2 newborn we were compelled to perform supravesical urinary drain and in 3 children a suprapubic drain. Secondary nephrectomy became necessary in 4 children, 3 of whom belonged to Risk Group I. In 23 of 57 children valve resection followed by transurethral drainage was the only therapy. In 22 of 57 children corrective surgery was performed subsequently (neo-implantation, with and without modellage, stenosis of the ureter exit). The article reports on the course in each case. PMID- 2321422 TI - [30 years of urethral valve treatment in Sweden]. AB - To achieve the best possible late results in valve treatment we think the following procedure would be mandatory: 1. Immediate transfer to a specialised hospital. 2. Acute diagnostics with correction of the water and electrolytes balance. 3. Suprapubic procedure is preferable over the transurethral approach if the catheter is expected to remain indwelling for a length of time. 4. The obstructing urethral valve is the primary object. 5. Resection is done only in 12 o'clock position in dorsosacral (lithotomy) position. 6. In rare cases with a severely constricted neck of the bladder it may be necessary to perform resection after Turner-Warwick. 7. In most cases it is possible to avoid surgical intervention at the upper urinary tract. 8. Regular follow-up checks are urgently recommended (sonography, x-ray, endoscopy, urodynamics). PMID- 2321423 TI - [Errors and dangers of various valve resection technics]. AB - Complications are frequently seen in patients with urethral valves, especially in the youngest age bracket. Some of the complications are due to valve obstruction and others due to the primary therapy. Valve resection can be transvesical, with or without symphysic incision, in direct view, via perineostomy or transurethral. These different methods represent a historical development. The mandatory prerequisite consists of the availability of update cystoscopic equipment for babies and infants. The main problems involved in "open" surgery concern incontinence. Transurethral approach can result in strictures; incontinence due to sphincter lesion can also occur. In recent years antegrade resection is being performed via percutaneous transvesical approach. It may be expected that this reduces the complications, but there is still insufficient experience to permit final assessment. PMID- 2321424 TI - [Urodynamics of urethral valve resection]. AB - Basing on the cases of 8 children with urethral valves who were diagnosed and treated during the first year of life we report on the urodynamic results. It is concluded that after valve resection enhanced pressure levels may still exist during micturition for some time even if the flow of urine has become normal. A morphologically and functionally satisfactory treatment result (separate lasix clearance on both sides) can be expected only after the pressure has dropped, a phenomenon that often occurs spontaneously. PMID- 2321425 TI - Obstructive jaundice in Kawasaki's disease. AB - We describe a case of Kawasaki's disease in a 10-year-old child who had obstructive jaundice, intrahepatic biliary duct dilatation and gallbladder hydrops. The diagnosis was defined by echography, CT-scan and cholangiography. Immediate relief from symptoms and progressive resolution of jaundice was achieved by percutaneous transhepatic biliary drainage (PTBD). Laparotomy was avoided. PMID- 2321426 TI - Carcinoma of the breast in children. AB - Carcinoma of the breast in children is an extremely rare disease, only 44 patients have been reported in the world literature. We report on a case of breast cancer in a 9-year-old girl, who was admitted to the hospital because of a four-month history of a painless mass in the right breast. Clinical examination and mammography resulted in a strong suspicion of malignancy. The histology corresponded to juvenile secretory carcinoma, the histological type without the characteristics of prepubertal cancer cases. Electron microscopy demonstrated intracellular large vacuoles and acini filled with secretory material. The mitotic index was low, the highest measured value was 4 mitotic figures per 10 high power fields corresponding to 2.78 mitotic figures per mm2 of epithelium in the microscope field. Flow cytometry showed that the neoplastic cells were diploid and had a low S-phase fraction. A simple mastectomy including axillary evacuation was performed. No lymph node or distant metastases were found. Postoperative radiation treatment or chemotherapy were not administered. Our patient has been in follow-up for six years without recurrence. In this case simple mastectomy with axillary evacuation seems to have given a cancer-free development into adulthood. Earlier reports have also shown a favourable outcome in these tumours. PMID- 2321427 TI - A symmetric double monstrosity. PMID- 2321428 TI - Vital reactions to frostbite of the ear and paw skin in guinea pigs exposed to the cold. AB - Vital reactions to frostbite in the paw and ear skin of guinea pigs were studied in order to find an animal model for frostbite in cases of accidental hypothermia. One group of animals was rendered hypothermic (rectal temperature, 30 degrees C) by exposure to an ambient temperature of -20 degrees C, and samples were taken from the frozen skin. A second group was rendered hypothermic and rewarmed in warm air at 45 degrees C, and samples were taken from the thawed skin. The only vital reaction in the first group (freezing time, 4-5 h) was mild initial inflammation, which was expressed in granulocyte adhesion to the vessel wall and the migration of a few cells into the dermis. The inflammatory reaction was more distinct in the second group (freezing and thawing together 5-7 h), with a large number of granulocytes being present in the dermis. Oedema and hyperaemia were also present in the frostbitten tissue after thawing, but no signs of necrosis developed. The alkaline-phosphatase reaction demonstrated the presence of granulocytes more clearly than H & E or Masson trichrome staining. Vital reactions were more advanced in the ear skin. It is concluded that vital reactions are very scarce in cases of frostbite, even after several hours' exposure, unless the tissue is allowed to thaw. PMID- 2321429 TI - [Use of rectal temperature-time of death nomograms at the scene of death]. AB - The application of the rectal temperature time of death nomogram at the scene of death by 11 authors from 6 lego-medical institutes resulted in a standard deviation of the differences between nomographic and real death time of +/- 1.3 h in 46 cases (group I) with met requirements and clearly defined points of contact, nevertheless, including 9 cases with a more progressive cooling (0.5 greater than Q greater than or equal to 0.2). In cases with a real death time of more than 4h (N = 26) the standard deviation was +/- 1.0 hours corresponding to permissible variation of 95% of +/- 2.0 hours. Consequently, the permissible variation of 95% was much smaller than that suggested by the nomogram. The nomographic death time interval did not agree with the real one in 5 cases out of additional 30 cases with recognizably unsure points of contact (group II). PMID- 2321430 TI - [The significance of anticipating suspected brain death for the accusation of failure to treat according to Section 323c of the Federal Penal Code]. AB - Brain death is usually not confirmed by neurological and angiographical techniques until long after it has actually taken place. In connection with a case in which expert testimony was heard, clinical and radiographic evidence and the autopsy statement are discussed as criteria of continuing development of brain edema; on the basis of the evidence it was possible to conclude that the cerebral circulation had not yet ceased at the time assumed. PMID- 2321431 TI - [Ultrastructural pathology of mechanical skeletal muscle damage]. AB - In continuation of previous light microscope investigations the question has been raised whether the criteria determined for vital muscle damage using light microscopy, could be verified and perhaps extended for the ultrastructural region. In addition to existing human pathological material taken early post mortem, muscle tissue obtained from animal experiments was also examined. The evaluation concentrated on the muscle cells, the cell organelles and the contractile apparatus. An evaluation of semi-thin-sections was carried out in parallel. The following reaction patterns could be defined as vital reactions: hypercontraction bands, zones of rupture in narrow topological relationship to organelle changes, microstructure changes with disintegration of the fibre structure, subsarcolemmic and interfibrillary oedema, decomposition of the sarcolemma. The earliest vital reactions were detectable after only a few minutes survival time. The comparison between the results of animal experiments and human pathology and the application of the results to forensic pathology will be discussed. PMID- 2321432 TI - [Tablet residues in gastrointestinal contents? A polarization microscopy screening method for rapid evaluation at the autopsy table]. AB - When tablet residues are found in the gastrointestinal tract during autopsy, this does not only indicate the possible presence of intoxication, but may also provide indications with the regard to the kind of intoxication (e.g. suicide) if the amount of tablets is considered. If tablets have already dissolved and thus large portions can no longer be detected with the naked eye, a definitive appraisal with regard to the presence of tablet residues is often difficult or even impossible on the autopsy table. A polarization microscopic screening method is described which enables identification of characteristic tablet auxiliary substances (maize starch, sodium carboxymethyl starch, microcristalline cellulose or sodium carboxymethyl cellulose) to be identified immediately and simply in the gastrointestinal contents. It also enables a rapid orientative screening for tablet residues in glasses found or the fluid these contained as well as in aspirated material and vomit. If the active agent of the tablet can be detected by chemical toxicology, the polarization microscopic diagnosis of abundant tablet auxiliary substances is compatible with intake of large amounts of drugs, which makes self-administration highly probable. PMID- 2321433 TI - [Pediatric skull fractures and child abuse. A critical comment on the contribution "Experimental studies of skull fractures in the infant" by W. Weber]. PMID- 2321434 TI - Mortality and tumour incidence of Han:SPRD rats. AB - In a longevity study a total of 394 Han:SPRD rats (200 males and 194 females) were kept in a barrier type animal quarter from weaning until their natural death. The mean life span of males was 29.6 +/- 5 months, that of females 27.6 +/ 6.2 months. The most frequent neoplasms in females were mammary gland tumours (63.4%). Neoplasms of endocrine organs were common in animals of both sexes. Thyroid neoplasms, predominantly of C-cell origin, occurred in 60% of the males and 51.5% of the females. Pituitary gland tumours were observed in 53% of male and 45.1% of female rats. Further frequent tumours of the endocrine system included phaeochromocytomas (23% in males, 15.5% in females), adrenal cortex neoplasms (6% in males, 13.5% in females) and tumours of islet cells of the pancreas (20.8% in males, 8.2% in females). An uncommonly high incidence of squamous cell neoplasms (16% in males; 9.3% in females) of the preputial and clitoral gland was observed in this stock. Further organs frequently affected by neoplasms were the skin/subcutis and brain. PMID- 2321435 TI - Seromonitoring in small laboratory animal colonies. A five year survey: 1984 1988. AB - From 1984 to 1988 one thousand serologic investigations of laboratory animal colonies originating from 10 different European countries were performed. The most prevalent infections in mouse stocks were caused by Mouse hepatitis virus (MHV), Minute virus of mice (MVM), Theiler's encephalomyelitis virus (TEMV), Reovirus type 3 (Reo3), Sendaivirus, and Pneumonia virus of mice (PVM). In mice no infections with Lymphocytic choriomeningitis virus (LCM), Polyomavirus, Mouse adenovirus, and K-virus were recorded. Only two colonies were infected by Ectromelia virus. The first six virus infections of mice were also found in rat colonies as well as the rat-specific Coronaviruses (Sialodacryoadenitisvirus- SDA, Rat corona virus--RCV) and Parvovirus (Kilham rat virus--KRV, Toolan H-1 virus) being endemic. Antibodies to Bacillus piliformis were detectable in about 50% of rat stocks screened. This is in contrast to the mouse, where only about 10% of the colonies were found to be positive. A similar picture was seen for M. pulmonis which is primarily an infection of the rat. In mice no case was detected during the last two years. The number of investigations performed from guineapig, hamster and rabbit colonies was relatively low. Nevertheless, antibodies against the following antigens were detectable: In guineapig stocks: Reo3, PVM, Sendai, Simian virus 5 (SV5) and B. piliformis; in rabbits: Reo3, Sendavirus, SV5, and B. piliformis; in hamsters: PVM, LCM and B. piliformis. The overall contamination rate showed a continuous decrease until 1988. Nevertheless, about 50% of mouse and rat stocks still exhibited antibodies to one or more viral infections. PMID- 2321436 TI - [Comments on the work of Bundschuh, G., and Madry, M.: "atwp-mutants in an albino mouse subtype (AB/Hum-1)," Z. Versuchtierkd. 1988; 31: 249-254]. PMID- 2321437 TI - The effect of food restriction by time-scheduled feeding on the development of body-weight, lifespan and incidence of spontaneous tumours and diseases in male Han:SPRD rats. AB - Food consumption, development of body weight, lifespan and incidence of spontaneous diseases and tumours were investigated in 3 groups of 96 male Han:SPRD rats each maintained in a longevity study from weaning up to their natural death. All rats were fed a commercial cereal-based diet. One group received food ad libitum and was used as control group. Access to the diet was controlled in the other two groups by means of an automatic timer. The rats of one of the latter groups were fed nocturnally (4 x 42 min daily during the dark period) and those of the other adiurnally (4 x 42 min daily, each two times during dark and light period). Time-scheduled feeding caused an evident food restriction compared with the food consumption of the rats fed ad libitum. This food restriction, however, was significantly more pronounced in the younger animals during the first weeks after weaning than in the older rats. The body weight development corresponded to the feed intake. In animals subjected to food restriction the weight remained below that of rats fed ad libitum during all age periods. Furthermore, time-scheduled feeding caused an important increase of the mean life expectancy and a reduction in the incidences of chronic nephropathy and purulent and chronic forms of prostatitis. Only a slight effect of controlled feeding was observed on the incidence of alveolar lipoproteinosis. Time-scheduled feeding did not cause a reduction in the incidence of tumours, but it delayed their occurrence. The risk to develop various types of tumours during the third year of life was significantly higher in the ad libitum group than in the rats fed by a controlled regime. The automaton Han:CHRONOFEEDER, used in this study, has proved to be an appropriate, relatively inexpensive and easily installable feeding system for automatic control of food accessibility. It is suitable to implement controlled feeding and food restriction of rodents in longterm experiments. PMID- 2321438 TI - The significance of timing of metronidazole prophylaxis and addition of fosfomycin in colorectal surgery. An experimental study in rats. AB - A novel approach to antibiotic prophylaxis in colonic surgery, suggested by our previous clinical experience, was experimentally tested. Intravenous administration of metronidazole or fosfomycin at greater than or equal to 4 hours before surgery effectively prevented lethal infectious complications, whereas metronidazole prophylaxis begun at induction of anaesthesia proved to be much less efficacious (4% and 43% deaths vs. 50% among controls, p less than 0.001 and p greater than 0.7, respectively). The in vivo efficacy of antibiotic prophylaxis correlated better with mucosal counts of Clostridium and Bacteroides than with luminal counts of aerobic or anaerobic bacteria. Earlier initiation of intravenous metronidazole prophylaxis thus markedly increased its in vivo efficacy, apparently due to preoperative mucosal suppression of endogenous potential pathogens. This 'early timing' approach to systemic prophylaxis against infection in abdominal surgery warrants further evaluation both for other antibiotics and clinically. PMID- 2321439 TI - Long-term survival in sporadic and familial medullary thyroid carcinoma with special reference to clinical characteristics as prognostic factors. The Swedish MTC Study Group. AB - All the 249 patients with medullary thyroid carcinoma (MTC) diagnosed during a 23 year period in Sweden were followed up completely for 4-27 years. The overall relative survival was 79.9% at 5 years after diagnosis and 68.6% at 10 years. After 5 years of follow-up, the relative survival rate was 5 percentage points higher in females than in males; 30 percentage points higher in patients aged less than 40 than in those 60-69 years at diagnosis; 24 percentage points higher in patients with familial disease detected at screening than in those with sporadic MTC; 20, 26 and 48 percentage points lower in patients with stage II, III, and IV, respectively, than in those with stage I; and almost 30 percentage points lower in the group of patients with a large tumor (greater than 3 cm) than in the group with a small one (less than 1 cm). In multivariate proportional hazards analyses of all these important determinants of outcome, the prognostic information provided by age and stage was still significant when several morphologic characteristics were taken into account (nuclear DNA content, calcitonin immunoreactivity, amyloid content, argyrophil reaction and state of the tumor capsule). PMID- 2321440 TI - Combined cervicothoracic approach in thymectomy for myasthenia gravis. AB - Thymectomy was performed for myasthenia gravis on 30 patients, using a new approach with a collar incision which gave full exposure of the retrothyroid space and was directly connected to a median sternotomy. The thymus was removed en bloc without pleural incision. There was no perioperative mortality and the only complications were transient respiratory insufficiency in two cases. The postoperative hospital stay was 3-9 (mean 5.8) days. The effect of thymectomy was evaluated after 2-8 years at the Department of Neurology, when changes in symptoms (stages I-IV) or medication (need for cholinesterase inhibitors) were registered. The total clinical improvement rate was 97%, with 3% of the patients improved three stages, 33% two stages and 60% one stage compared with the preoperative classification. Twenty patients (67%) were asymptomatic at follow-up and six (20%) also required no medication. The medication need was reduced in 70% of cases (mean reduction 42%). Our cervicothoracic approach resulted in the same rate of improvement as in studies using more extensive transsternal procedures, but the morbidity was lower, with no complications requiring prolonged hospital stay. The morbidity was also less than after only transcervical procedures aiming to perform total thymectomy--a prerequisite for maximal and lasting benefit from surgery. Moreover, as this cervicothoracic approach is simple and safe, it can be recommended as an option in the surgical management of myasthenia gravis. PMID- 2321441 TI - Risk factors for rupture of abdominal aortic aneurysm. Clinical review. PMID- 2321442 TI - Splenectomy for haematological diseases. AB - Two hundred patients with various haematological diseases underwent splenectomy between 1974 and 1986. The diagnoses were: Hodgkin's disease (n = 76), hairy cell leukaemia (n = 25), idiopathic thrombocytopenic purpura (n = 20), chronic lymphatic leukaemia (n = 19), haemolytic anaemia (n = 18), non-Hodgkin lymphoma (n = 16), myelofibrosis (n = 10), chronic myeloid leukaemia (n = 6), spherocytosis (n = 4), and miscellaneous (n = 6). Many of the patients were treated with corticosteroids and in poor general condition, partly as a result of chemotherapy. There were 37 postoperative complications in 29 patients (14.5%); two died, both of septicaemia. Pneumonia, bleeding, and wound infection were the most common complications, occurring in 9, 8, and 6 patients, respectively. Twelve patients required reoperation, eight for bleeding, two for intra-abdominal abscesses, and one each for pancreatitis and bowel perforation. There was no association between the diagnosis and the type of postoperative complication, but patients whose spleens weighed more than 2 kg had an increased incidence of postoperative complications (30%). We conclude that elective splenectomy is a safe treatment for haematological diseases, even in high risk patients. PMID- 2321443 TI - Extracorporeal shock-wave lithotripsy of bile-duct stones. Initial Swedish experience. AB - Fifteen patients with mean age 74 (range 34-94) years were treated with extracorporeal shock-wave lithotripsy (ESWL) for bile-duct stones (intrahepatic in 4 cases) following failure of surgical or endoscopic treatment. A Dornier HM3 lithotriptor was used, and in all cases the ESWL session was preceded by establishment of external biliary drainage (endoscopic nasobiliary in 9, percutaneous transhepatic in 2 and a surgical T-tube in 4 cases) for radiologic positioning of stone. Endoscopic (14 cases) or surgical (1 case) sphincterotomy was done to facilitate spontaneous passage or endoscopic removal of fragments after ESWL. General anesthesia was not needed during the average 50 (range 25-65) min required for performance of ESWL. The number of delivered discharges was 750 to 2,100 and the generator voltage varied from 14 to 17 kV. Disintegration of stone was good in 12 cases and partial in two. Ten patients remain stone-free, five after spontaneous passage, and five after endoscopic extraction of fragments. There were few complications. ESWL may be useful in high-risk patients with failed endoscopic treatment of bile-duct stones and for management of intrahepatic stones. PMID- 2321444 TI - Colposcopy of patients with cytologic inflammatory epithelial changes. AB - Of 3,308 cervical cytologies performed at a university health service between September 1986 and September 1987, 371 were reported as showing inflammatory epithelial changes (IECs). Colposcopy was offered to all patients with this diagnosis and was actually performed on 200 (54%). Of these women, 44 had an atypical transformation zone; of the 33 who were biopsied, 23 had histologic diagnoses ranging from human papillomavirus (HPV) infection (4 cases) to grade III cervical intraepithelial neoplasia (CIN; 4 cases). Most biopsies showed CIN I. In our clinic, the 95% confidence limits for the histologic diagnosis of HPV or CIN in women with a cytologic diagnosis of IEC are 8.5% to 23.5%. Colposcopic examination of women with IEC may be able to detect patients with CIN who are missed by standard cytologic screening. Concerns about a potential bias from false-positive histology reports must be resolved before such an approach can be recommended. PMID- 2321445 TI - Reliability of a quantitative interpretation of sputum cytology slides. AB - A sputum cytology method has been developed in which eight cytologic components associated with stimulation of the bronchial airways are quantified. The extent to which cytotechnologists could reliably and consistently utilize this system was measured. In an initial study (study A), four cytotechnologists had an overall intraobserver agreement of 90.2% and an interobserver agreement of 76.3%. There was an overall agreement with the laboratory standard of 85.6%. The most difficult components to consistently rate were mucous spirals and metaplastic, dysplastic and columnar cells. Study B was initiated after the implementation of a training program designed to better define both cytologic criteria and our system of quantitation. Two of the original cytotechnologists and a newly trained cytotechnologist participated in study B. The overall intraobserver agreement increased to 97.8% while the overall interobserver agreement increased to 97.5%. The overall agreement with the laboratory standard was 98.3%. These results indicate that a cytologic rating system employed for quantitative sputum cytology can be taught and applied reliably and consistently. PMID- 2321446 TI - Discriminant analysis of lower respiratory tract components associated with cigarette smoking, based on quantitative sputum cytology. AB - Cigarette smoking is the major contributor to chronic bronchial irritation, and tobacco smoke is the most common bronchial carcinogen. A newly developed quantitative sputum cytology test was applied to three-day-pooled, spontaneously produced sputa collected from 349 cigarette smokers and 93 patients who had never smoked; the samples were processed by the Saccomanno technique. In addition to identifying malignant and precancerous cells in sputum, this test identifies eight morphologic parameters of bronchial irritation. Cross-sectional analysis of the cytologic data indicated that, within a 99% confidence interval, cigarette smokers had statistically significantly higher levels of all eight components, producing a unique profile. Discriminant analysis revealed that pigmentation of macrophages, alveolar macrophages and mucous spirals (in that order) were the leading components differentiating smokers from nonsmokers. This new quantitative sputum cytology test correlates with the model of lung carcinogenesis. The detection of proliferative cellular alterations, such as benign and early atypical metaplasia, represent the detection of chronic persistent irritation, which is considered to be a reversible change. The ability to monitor individual responses to toxic inhalants (before the development of irreversible disease) by utilizing a noninvasive test represents a unique opportunity to impact the historic course of lung carcinogenesis. PMID- 2321447 TI - Transthoracic needle aspiration biopsy in Wegener's granulomatosis. Morphologic findings in five cases. AB - Percutaneous needle aspiration biopsies of the lung from five patients with Wegener's granulomatosis were reviewed. Three of the patients presented with the generalized form of the disease while two presented with the limited pulmonary form; one of the latter subsequently developed disseminated disease. The morphologic findings in the pulmonary aspirates were similar in all cases. The cytologic preparations contained neutrophils entrapped within necrotic debris plus scattered but prominent histiocytic giant cells, which often had nuclei arranged in rings or horseshoes, in a background of lymphocytes, epithelioid histiocytes and reactive pneumocytes. Cell block preparations showed discrete areas of necrosis containing a neutrophilic infiltrate and focally palisaded by epithelioid histiocytes. The intervening viable tissue contained prominent histiocytic giant cells and chronic inflammatory cells enmeshed in a fibrous matrix. One cell block contained a small artery with a small focus of possible granulomatous arteritis. While an open lung biopsy is generally required for a definitive diagnosis, the pathologist may encounter unsuspected Wegener's granulomatosis in a needle aspirate. Recognition of the findings observed in these cases should alert the pathologist to the possibility of Wegener's granulomatosis so that an open lung biopsy can be performed if clinically indicated and cytotoxic therapy can be promptly instituted if the diagnosis of this entity is confirmed. PMID- 2321448 TI - Nipple discharge cytology in mass screening for breast cancer. AB - Since 1977 mass screening for breast cancer has been conducted in Miyagi Prefecture, Japan; inspection, palpation and cytologic examination of any nipple discharge are part of the initial screening procedures. Among 149,681 subjects examined, 404 cancer cases and 63 papilloma cases were detected. The nipple discharges from 20,537 women were examined cytologically; of the 61 cancer cases, the smears were positive in 18 cases, suspicious in 7, negative with atypical findings in 12 and negative in 24. Ten of the cancer cases were detected exclusively by the cytologic examination of a nipple discharge. In eight of these ten cancer cases, there was no other initial evidence of the primary tumor. The cytologic diagnosis of discharges without blood from 28 cancer cases was positive or suspicious in 10 cases and negative in 18. Thirty-seven of the papilloma cases were initially detected only by the cytologic examination of a nipple discharge; neither physical examination nor mammography showed any abnormal findings. PMID- 2321449 TI - The value of needle aspiration cytology of the breast, with an emphasis on the diagnosis of breast disease in young women below the age of 30. AB - Our experience with 4,739 needle aspirations of the breast was reviewed, with an emphasis on the diagnosis of carcinoma in young women under the age of 30 years. Among benign diseases, fibroadenomas were most frequently seen in younger women (24.3% of 919 cases) while cysts were most frequently seen in women 30 years of age and older (20.0%). Fibrocystic conditions were identified in approximately 30% of the women in each group. All younger women with suspicious diagnoses had fibrocystic disease at biopsy; in older women, 75% of the suspicious cases proved to be carcinomas while 25% proved to be fibrocystic diseases. Carcinomas were diagnosed cytologically in 1.3% of younger women and in 9.7% of older women. In young women, in whom breast carcinoma is a rare disorder, it is important that carcinoma be diagnosed without delay so that an appropriate plan of management can be adopted. These findings suggest that needle aspiration cytology can accurately make that diagnosis. PMID- 2321450 TI - Metastatic breast carcinoma in pleural fluid. Correlation of morphology with estrogen receptor activity and morphology of the primary carcinoma. AB - Sixty-nine breast carcinoma patients with malignant pleural effusions were studied (1) to compare the morphology of the carcinoma cells in the effusions with the morphology in the primary carcinomas and (2) to correlate the morphologic findings with the estrogen receptor (ER) activity of the carcinomas and with the survival of the patients. Twenty-six patients had effusions containing carcinoma cells forming hollow spheres (morula-positive cases) while 43 had pleomorphic tissue fragments or tumor giant cells or both (morula-negative cases). Twenty-nine of 44 primary carcinomas with hormone receptor determination were ER positive. The median survival of patients with ER-positive tumors was 77 months while the median survival of ER-negative patients was 46 months. Thirteen patients with morula-positive effusions and 16 patients with morula-negative effusions had ER-positive primary carcinomas (P less than .001). Thirteen of 17 patients with morula-positive effusions and 4 of 23 patients with morula-negative effusions had duct or tubule formation in their primary carcinomas (P less than .001). The median survival of 26 patients with morula-positive effusions was 92 months, compared with 49 months for 43 patients with morula-negative effusions (P less than .001). Patients with ER-positive/morula-negative carcinomas had a significantly better survival rate than did patients with ER-negative/morula negative carcinomas, but a significantly poorer survival rate than did patients with morula-positive carcinomas. PMID- 2321452 TI - Cytologic diagnosis of Campylobacter pylori-associated gastritis. AB - Forty-nine paired gastric brushings and biopsy specimens were reviewed to determine the cytologic presentation of Campylobacter pylori-associated gastritis. The bacterium was identified in ten routinely prepared cytologic specimens, seven of which were positive for C pylori by biopsy. C pylori could be readily distinguished from other bacteria and was accompanied by inflammation and reparative atypia of gastric epithelial cells. Gastric brushing cytology is an effective method of diagnosing C pylori-associated gastritis. PMID- 2321451 TI - Solitary angiomyolipoma of the liver. Report of a case initially examined by fine needle aspiration biopsy. AB - Transabdominal fine needle aspiration biopsy of a solitary space-occupying lesion in the liver produced smears containing irregular bundles of smooth muscle cells with granular or fibrillary cytoplasm and slightly pleomorphic nuclei. In a few bundles, aggregates of mature fat cells were present, which is characteristic for an angiomyolipoma. Histologic examination of the resected mass showed it to be a solitary angiomyolipoma of the liver. The diagnosis was further confirmed by immunohistochemical and electron microscopic studies. PMID- 2321453 TI - Critical evaluation of the cytodiagnosis of fibrogastroendoscopic samples obtained under direct vision. AB - The reliability and efficiency of the cytodiagnosis of fibrogastroendoscopic biopsy samples obtained under direct vision in 676 cases during a five-year period were reviewed. The critical evaluation showed a cytodiagnostic sensitivity of 93.54%, a specificity of 98.79%, a false-negative rate of 6.46%, a false positive rate of 1.21%, a predictive value of a positive result of 98.01%, a predictive value of a negative result of 96.00%, a prevalence rate of 38.91%, an overall diagnostic accuracy of 96.75% and a chi-square value of 5.50 (P less than .05). These results were comparable to those obtained by histologic study in the same cases; the combined use of both cytology and histology to analyze the samples obtained gave the best results. These findings reemphasize the important role of fibrogastroendoscopic cytodiagnosis in establishing the existence of gastric cancer and shows that the technique is accurate and efficient. The types of statistics useful for assessing such data are discussed. PMID- 2321454 TI - Brushing cytology in biliary tract obstruction. AB - During a period of eight years (1980 to 1987), cytologic samples were obtained by brushing and reverse screw devices from 54 patients undergoing transhepatic cholangiography for evaluation of obstructive jaundice. Eight patients were excluded from this study, seven for inadequate follow-up and one because of unsatisfactory cytologic material. Of the remaining cases, 32 were cytologically diagnosed as adenocarcinomas; all but one patient proved to have malignant disease by histologic examination and/or through clinical follow-up. These included 21 pancreatic carcinomas, 6 bile duct carcinomas, 1 ampullary carcinoma, 1 gallbladder carcinoma and 2 metastatic carcinomas. In one case, the diagnosis of malignancy was found to be in error upon review of the cytologic smears. Of 14 patients with negative cytologic diagnoses, 7 were found to have malignant neoplasms and 7 had benign diseases. These findings indicate that, while a positive cytologic diagnosis is a reliable indicator of a malignant biliary obstruction, a negative result does not exclude malignancy. PMID- 2321455 TI - Fine needle aspiration cytology of eyelid tumors. AB - Fine needle aspiration (FNA) biopsy was performed on 19 patients with eyelid masses. Six of the patients also had preauricular/submandibular nodal enlargements aspirated. Histopathologic study was performed in ten of the cases. FNA cytology made the diagnosis of an epithelial malignancy in 17 cases (10 sebaceous carcinomas, 4 poorly differentiated carcinomas, 2 squamous cell carcinomas and 1 malignant melanoma). The diagnostic accuracy of FNA cytology in evaluating eyelid masses was thus 89.4%; there were two false-negative cases. All nodal FNA smears revealed metastases of the respective primary tumors. This study indicated that FNA cytology is a simple and efficient method for making the diagnosis of malignancy in eyelid masses, especially in those patients who are not suitable candidates for surgery. Subsequent nodal metastases and tumor recurrence were detected without difficulty using FNA smears. PMID- 2321456 TI - Conjunctival brush cytology. AB - In order to collect conjunctival cells efficiently, we developed a special brush that is a modification of the Cytobrush used in cervical cytology. The conjunctival brush is small and made of nylon bristles. Cells collected by these brushes were rinsed into a buffered solution, from which filter preparations were made. This technique produced adequately cellular samples from temporal bulbar conjunctiva; these preparations stained well with the Papanicolaou stain. Under normal conditions, three cell types were observed in the brushing samples; one was the polygonal epithelial cell, the second type was a small rounded cell, and the third type was a mucus-secreting goblet cell. Samples from dry-eyed patients contained keratinized cells with or without a decrease in goblet cells. Elongated cells were seen in samples from postirradiation and postoperative patients. Irritation caused by the brushing was of the same intensity as irritation caused by collecting cytologic specimens by impression or by the use of cotton swabs. These findings suggest that brushing cytology of the conjunctiva is a relatively noninvasive technique and can provide valuable information for evaluation of conjunctival conditions. PMID- 2321457 TI - Fine needle aspiration biopsy of orbital meningioma. Report of a case. AB - A case of orbital neoformation in a 28-year-old man is described. The cytohistologic diagnosis on fine needle aspiration biopsy specimens was meningioma; this was later confirmed by histologic study of surgical fragments. The cytohistologic features of the aspirated material (nuclear pseudoinclusions, psammoma bodies and cells arranged in whorls) allowed a rapid, reliable, ambulatory diagnosis to be formulated with an advantageous cost/benefit ratio. PMID- 2321458 TI - Cytomorphologic features of the rare epithelial-myoepithelial carcinoma of the salivary gland. AB - The cytomorphologic features of an epithelial-myoepithelial carcinoma arising in the submandibular gland are reported. The aspiration smears were cellular, with two cell types present: dark cells showing attempted gland formation and clear cells with vacuolization. The clear cells frequently formed globular masses and had indistinct cytoplasmic membranes. These globular masses of clear cells were usually adjacent to the fragments of dark cells. A striking feature was the presence of numerous naked nuclei. PMID- 2321459 TI - Epithelial-myoepithelial carcinoma of the salivary gland. Fine needle aspiration cytologic findings. AB - A case of epithelial-myoepithelial carcinoma of the salivary gland in a 78-year old patient is presented. Fine needle aspiration cytologic smears showed a moderate number of tumor cells arranged in three-dimensional, well-outlined clusters reminiscent of the ball-like structures of adenoid cystic carcinoma. The nuclei were small and monotonous, with finely granular chromatin and small nucleoli. A large number of cells showed abundant clear cytoplasm; however, in some of the clusters the cytoplasms were very scant, again mimicking adenoid cystic carcinoma. Fragments of pale homogeneous acellular material, isolated or surrounding the cellular clusters, were another conspicuous finding. PMID- 2321460 TI - Osteoclastomalike anaplastic carcinoma of the thyroid. Diagnosis by fine needle aspiration cytology. AB - Fine needle aspiration (FNA) of a neck mass yielded cytologic specimens containing two cell populations: multinucleated giant cells and smaller, round-to oval, undifferentiated malignant cells. The giant cells were frequently so numerous as to obscure the other cells. The FNA cytodiagnosis of a rare anaplastic thyroid carcinoma containing osteoclastic giant cells was substantiated by the subsequent exploratory surgery and biopsy specimen. Immunohistochemical staining suggested a dual origin of the two cell populations. PMID- 2321461 TI - Fine needle aspiration cytology of thyroid gland diseases. AB - From 1982 to 1987, 2,433 lesions of the thyroid gland in 1,796 patients were examined by fine needle aspiration (FNA). Cytopathology classified 66.91% of the aspirates as benign, 10.76% as thyroiditis, 4.89% as suspected (unspecified) neoplasia, 1.31% as positive for malignancy and 16.11% (392) as unsatisfactory. The histologic diagnoses in 257 cases were compared with cytologic diagnoses to determine the accuracy of FNA cytology of thyroid lesions, yielding a sensitivity of 71.43%, a specificity of 100% and an accuracy of 95.09%. This data strongly supports thyroid FNA as an important preoperative diagnostic tool. Follicular carcinomas were difficult to cytologically differentiate from nonmalignant follicular neoplasms, and papillary thyroid carcinomas less than 2 cm in diameter in elderly patients were frequently misdiagnosed or diagnosed only as "suspect lesion." PMID- 2321462 TI - Posttransplant mediastinal Burkitt-like lymphoma. Diagnosis by cytologic and flow cytometric analysis of pleural fluid. AB - Cytologic and flow cytometric (FCM) analyses of pleural fluids established the diagnosis of a Burkitt-like posttransplant lymphoma with a unique mediastinal presentation. FCM analysis of pleural fluid specimens was especially helpful in determining the cell lineage. PMID- 2321463 TI - Fine needle aspiration biopsy in the diagnosis of apocrine sweat gland adenocarcinoma. PMID- 2321464 TI - A rapid and simple assay to prevent over-treatment of ovarian carcinoma. PMID- 2321465 TI - Use of recycled ethyl alcohol as a smear fixative. PMID- 2321466 TI - Multinucleation and abortive cellular division in human papillomavirus infection. PMID- 2321467 TI - Program of plenary sessions and advance abstracts of short communications. 34. Symposium Deutsche Gesellschaft fur Endokrinologie. Hannover, March 14-17, 1990. PMID- 2321468 TI - Students and pediatrics--a special challenge. PMID- 2321469 TI - Insight into Albertan's opinions on the nursing profession. PMID- 2321470 TI - Twenty years of learning to care through nursing research. PMID- 2321471 TI - Group forms to address the lack of opportunity for doctoral education in nursing in Canada. PMID- 2321472 TI - Special issue on oral yeast infections. Proceedings of a joint meeting of the British Society for Mycopathology, the Danish Society for Mycopathology and the Swedish Society for Clinical Mycopathology. Gothenburg, September 1989. PMID- 2321473 TI - The crisis of child health in developing countries. PMID- 2321474 TI - Fecal alpha 1-antitrypsin in breast-fed infants is derived from human milk and is not indicative of enteric protein loss. AB - Alpha 1-antitrypsin is a serum protein commonly used as a marker of enteric protein loss. In this study, we have quantified alpha 1-antitrypsin concentration in human milk and its excretion by healthy term breast-fed infants. We found high concentrations of alpha 1-antitrypsin in early milk (0.3-0.6 mg/ml during the first week of lactation) while the concentration fell during subsequent weeks, being detectable through at least 3-4 months of lactation. Significant quantities of intact alpha 1-antitrypsin were found to be excreted by the breast-fed infants studied. The amount excreted was typically higher in early weeks (as much as 200 mg/24 h) and decreased with infant age, possibly due to both decreased intake from the milk as well as increased digestion of the protein by the maturing infant. In vitro studies demonstrated that the trypsin-alpha 1-antitrypsin complex resisted proteolysis by pepsin and pancreatic enzymes; thus, alpha 1 antitrypsin in milk can escape gastrointestinal degradation. We conclude that alpha 1-antitrypsin is not a suitable marker for intestinal protein loss by term breast-fed infants. PMID- 2321475 TI - Nicotine and cotinine concentrations in the nursing mother and her infant. AB - Twenty-two smoking mothers and their healthy newborn infants (mean postnatal age of 3.7 days) were studied in the maternity ward. A close correlation was found (r = 0.94) between nicotine concentrations in the mothers' plasma and milk after smoking, the milk: plasma ratio being 2.9. The amount of nicotine transferred to the infant increased from 0.09 to 1.03 micrograms/kg infant body weight when mothers smoked before breast-feeding. The daily dose of nicotine via the mothers' milk was 6 micrograms per kg infant body weight. Cotinine but not nicotine concentrations in the plasma and milk of the mothers and the urine of the infants reflected the smoking habits of the mothers during pregnancy. There was no correlation between nicotine and cotinine concentrations in the infant's urine and the amount of nicotine given to the infant via the mother's milk. PMID- 2321476 TI - Somatosensory evoked potentials in neonatal jaundice. AB - Somatosensory evoked potentials (SEPs) were studied in jaundiced and normal neonates on the day the highest bilirubin values were reached, 2-3 days later, and at five weeks. During the first week three groups were formed according to peak bilirubin values: A: greater than or equal to 250 mumol/l (n = 20), B: 125 250 mumol/l (n = 6), C: less than 125 mumol/l or no jaundice (n = 19). At five weeks 10 infants of group A were reinvestigated, together with 17 controls. Cervical (N13) and scalp SEPs (N19) were recorded with a variable number of stimuli. The SEPs of group B and C did not differ from each other. In group A the N13 peak latencies were within the range of group C at the first investigation, but prolonged at the second and third. The cortical components were prolonged at the first investigation, improved but still prolonged at the second, while the N19 peak latency was still prolonged at the third investigation. The central conduction time (CCT) correlated positively with the bilirubin level. Since a rapid decrease in the N19 amplitude was found for all groups from 25 to 100 stimuli, recordings should be done with a low number of stimuli (less than 100). Our findings indicate that both the periferal and the central components of the SEPs in the neonatal period are delayed by jaundice and that full recovery is not obtained at five weeks. The non-invasive SEP technique can be used as a daily monitor of the effect of bilirubin on the CNS. PMID- 2321477 TI - Head circumference standards for Irish children. AB - A cross-sectional study measuring head circumference was performed on 3,344 Irish Children aged from 5 to 19 years. Comparison with other countries showed a slightly larger head circumference than the 1965 British standards produced by Tanner, but significantly smaller than the Ounsted data from Oxford. There was no significant difference between the urban and rural children, but the children of non-manual workers had a significantly larger head than those of manual workers. PMID- 2321478 TI - Congenital adrenal hyperplasia in Sweden 1969-1986. Prevalence, symptoms and age at diagnosis. AB - A retrospective study of all Swedish patients with congenital adrenal hyperplasia (CAH) born 1969-1986, was conducted to elucidate possible benefits of neonatal screening for CAH. Information was obtained about 150 patients (67 male, 83 female). One hundred and forty-three cases were regarded as classical and seven as non-classical (symptoms after 5 years of age or cryptic). All but two (one girl with 11-hydroxylase deficiency and one boy with beta-hydroxysteroid dehydrogenase deficiency) had 21-hydroxylase deficiency. The prevalence was 1:11,500. Ninety-three patients (48 male, 45 female) displayed salt loss, all before the age of 3 months. Two boys had died and many children had been critically ill during the first weeks of life. The median age at diagnosis for boys in this group was 21 days. Gender assignment was a major problem in 38 of 57 girls with ambiguous genitalia noticed during the first day. Fifteen of these girls were considered to be male for their first 40 days (median), before the CAH diagnosis was established. Patients in whom the first symptom was manifested after the age of one year often showed growth acceleration, which frequently was overlooked. Median diagnostic delay in this group was 17 months. Possible benefits of neonatal screening are: avoidance of a serious salt-loss crisis; earlier diagnosis and correct gender assignment in virilized girls; decreased virilization, growth acceleration and premature pubarche in prepubertal children; and reduced negative consequences for psycho-social development and final height. PMID- 2321479 TI - Effect of the long-acting somatostatin analogue SMS 201-995 on growth rate and reduction of predicted adult height in ten tall adolescents. AB - Ten adolescents (four boys and six girls) aged 11.5 to 17 years, presenting with constitutionally tall stature were treated with twice daily subcutaneous injections of 250 micrograms of SMS 201-995 (Sandostatin). Results are reported after 6 and 12 months of therapy. Reduction of growth rate was obtained in 9 patients and correlated with the reduction of 24-hour growth hormone pulsatility and with the decrease of plasma Somatomedin-C values. Moreover, acceleration of bone maturation on SMS 201-995 therapy occurred in seven patients, and mean bone age increased from 13.3 years to 14.5 and 15.8 years after 6 and 12 months of SMS therapy. The mean reduction of predicted adult height was 4.9 cm at the last evaluation after 6 or 12 months of therapy. The dual effect of SMS 201-995 on growth rate and bone maturation suggests that it may be an alternative treatment to reduce adult height. PMID- 2321480 TI - Standards for growth and final height in Turner's syndrome. AB - Data on birth, growth and final height were collected retrospectively for 78 women with Turner's syndrome born 1955-66. Seventy-one had received estrogen treatment from a mean age of 17.7 years (SD = 2.0 years), while 7 were spontaneously menstruating. At birth Turner girls were 440 g lighter (p less than 0.001) and 1.4 cm shorter (p less than 0.001) than 46,XX girls. Standards for untreated growth were established for the age period 6.5-17.5 years, while growth after 17.5 years was described in both untreated and estrogen treated women. Analysis of growth pattern showed that though no pubertal growth spurt was present, the steady decrease of height velocity (HV) was interrupted at the age of 9 years. HV was then constant until 12 years of age, whereafter it slowly decreased. Mean final height (FH) was 146.8 cm (SD = 5.8 cm, n = 76) compared to 166.8 cm in the general female population. No difference was found between 45,X women and women with other karyotypes (p greater than 0.7). Correlations between FH and parental heights, birthweight and birthlength were similar to those reported for normal women (19). FH varied with age at diagnosis. Those diagnosed after 17 years of age had a mean FH = 151.3 cm, while those diagnosed before had a mean FH = 145.8 cm (p less than 0.001). PMID- 2321481 TI - Metabolic and cardiovascular responses to exogenous triiodothyronine favour nontreatment of a girl with familial receptor-positive thyroid hormone resistance. AB - A father and daughter with inappropriate TSH secretion due to generalized relative receptor-positive thyroid hormone resistance are described. Minor variations of tissue peripheral resistance were observed in the adolescent girl. Shortened ankle reflex relaxation time and other clinical signs were consistent with a mild hyperthyroid state of the neuromuscular unit. The response of sex hormone-binding globulin concentration, 24 hour-ECG data and left ventricular echocardiographic parameters to increasing doses of triiodothyronine confirmed an euthyroid state of heart and liver tissue in the presence of excess thyroid hormone. Based on these findings and the benign course of the disease, treatment was withheld. Careful assessment, including echocardiography and 24 hour-ECG, of the functional state of thyroid hormone target tissues during triiodothyronine administration is recommended in these patients. No treatment is required when the functional state of the target tissues is eumetabolic. PMID- 2321482 TI - Diagnostic symptoms of severe and moderate haemophilia A and B. A survey of 140 cases. AB - With a view to the characterisation of presenting symptoms, a survey was made of 140 boys diagnosed as having haemophilia A or B, severe or moderate form, in Sweden during the years 1960-1987. Mean age at diagnosis was nine months for the severe cases and 22 months for the moderate cases. Although the heredity was known in 59/140 cases, 35 had had bleeding episodes before diagnosis had been established, thus emphasising the importance of genetic information and carrier identification in haemophilia families. Of the presenting symptoms, subcutaneous bleedings constituted 41% while joint and muscle bleedings were uncommon; 16% were bleedings in conjunction with puncture of vessels, injections or surgery. Fourteen percent had anaemia and received blood-transfusion at diagnosis; 9% were diagnosed post-neonatally but 20% had shown abnormal bleeding tendency already in the neonatal period; seven boys (5%) had intracranial haemorrhages, five of them neonatally. A thorough family history and an extensive investigation of bleedings in the neonatal period should make early diagnosis possible. PMID- 2321483 TI - Natural history of allergic diseases in children. AB - Questionnaire data from 1335 14-year-old children with a history of past or present asthma, allergic rhinitis or eczema were analysed regarding age at onset and cessation of symptoms. Incidence of asthma and eczema was highest during the first years of life. Early incidence of asthma was higher in boys than in girls but the sex ratio equalized gradually during childhood. Early incidence of eczema was equal between the sexes but the proportion of girls increased gradually with later age at onset. In 24% of the children more than one symptom was found. Cessation of symptoms was common in asthma (55%), in particular in those with early onset (74%), but less common in eczema (34%). Cessation of symptoms was less common in both diseases when associated with other allergic symptoms. Incidence of allergic rhinitis was fairly constant during childhood and cessation of symptoms was uncommon. A high risk of allergic airways disease was found after early eczema. PMID- 2321484 TI - Epilepsy in hydrocephalic children. AB - Epilepsy and epileptogenic activity in EEGs were studied in 168 shunt treated hydrocephalic (HC) children, the mean age at first operation 1.62 years (SD 1.87). 80 patients (47.6%) suffered from epileptic seizures during the follow-up period (mean 8.9 years). The epileptic seizures appeared before the initial shunting, and after the first shunt implantation in 43 (25.6%). There was no correlation between epilepsy and the aetiology of HC, number of shunt revisions, or shunt infections. Sixteen patients suffered from seizures during the neonatal period. Generalized spike and wave activity (SWA) was seen in EEG in eight out of these, and only one was seizure-free at the end of the follow-up period. All eight patients with epileptic seizures during the neonatal period without generalized SWA in EEG were seizure-free, however. SWA was seen in the first EEG prior to shunting in 75/168 patients (44.6%). All those patients who did not receive prophylactic medication, developed epileptic seizures, whereas 68.1% of those who received prophylactic anticonvulsive medication remained free of seizures. Partial epilepsy after shunting manifested itself in 15 patients, but this did not correlate with the side of the shunt or with the side of the SWA in the EEG. Slit ventricles (SLV) developed in 75 patients during the follow-up period, while the ventricles remained normal or dilated in 66 cases (27 patients had no CT follow-up). Epilepsy manifested itself in 8 out of these 141 patients (2 SLV, 6 non-SLV) during the first postoperative year, and in 29 patients in the SLV group and one in the non-SLV group at some time after the first postoperative year. PMID- 2321485 TI - Chest X-ray appearances in pneumonia and bronchiolitis. Correlation to virological diagnosis and secretory bacterial findings. AB - Chest X-ray findings were related to virus diagnosis, age and secretory bacterial findings in 128 infants and children under 7 years of age with clinical pneumonia and bronchiolitis. They belonged to a cohort examined in connection with the introduction of rapid methods for virological diagnosis. Seventy-six children had a virus infection diagnosed by examination of nasopharyngeal secretion and/or by serological methods. Thirty-seven of these children were classified as having pathogenic bacteria of importance in the respiratory tract. Four groups were compared: virus infected children with or without bacteria in the secretion and the corresponding virus negative groups. The X-rays were normal significantly more often in the virus positive/bacteria negative group compared with the other groups. Alveolar pneumonia appearing as lobar or segmental consolidations ("lobar" pneumonia) was observed with equal frequency and without relation to bacterial findings in the virus positive and the virus negative groups. But it was more often observed in the respiratory syncytial virus (RSV) infected children under 6 months of age compared with the older RSV children. In comparison disperse alveolar infiltrations ("bronchopneumonia") mostly appeared in the virus positive group. Interstitial pneumonia and peribronchitis were often present together in children over 6 months of age. There was no significant difference in the X-ray appearances in the groups with and without bacterial findings in the tracheal secretion except for a higher frequency of normal chest radiographs in the bacteria negative group. PMID- 2321486 TI - Effects of varying energy intakes on nitrogen retention and growth in very low birthweight infants fed fortified human milk. PMID- 2321487 TI - Leptomeningeal cyst and vacuum extraction. PMID- 2321488 TI - Rapp-Hodgkin ectodermal dysplasia. AB - A rare case of ectodermal dysplasia--the Rapp-Hodgkin syndrome--is presented. Its diagnosis is discussed and the importance of a multidisciplinary management and genetic counselling outlined. PMID- 2321489 TI - The role of European specialists in training overseas post-graduates in paediatric gastroenterology and nutrition. Report of a Workshop of the European Society for Paediatric Gastroenterology and Nutrition, Copenhagen, 1988. PMID- 2321490 TI - Comment on the composition of cow's milk based follow-up formulas. ESPGAN Committee on Nutrition. PMID- 2321491 TI - Antioxidant nutrients and immune functions. Proceedings of the Agricultural and Food Chemistry Division of the American Chemical Society, Symposium on Antioxidant Nutrients and the Immune Response. September 29, 1988, Los Angeles, California. PMID- 2321492 TI - Studies on membrane lipid peroxidation in omega-3 fatty acid-fed autoimmune mice: effect of vitamin E supplementation. AB - Enzyme-dependent and non-enzymatic in vitro lipid peroxidation was studied in autoimmune prone B/W mice fed diets containing high levels of dietary corn oil (CO) or menhaden fish oil (FO) as lipid source since weaning. Lipid analysis revealed that FO-fed mouse liver mitochondrial and microsomal membrane fractions incorporated 20:5 omega 3 and 22:6 omega 3 in replacement of 18:2 omega 6 and 20:4 omega 6 found in corn oil (CO) fed control animals reflecting the composition of the dietary oils. Lower concentrations of vitamin E were found in the FO-fed mouse membranes and serum than those of CO-fed mice when diets were supplemented with a standard 75 I.U. alpha-tocopheryl acetate/kg diet. The rate and extent of membrane lipid peroxidation was greatly increased in FO-fed, vitamin-E-depleted membranes. Full repletion of membrane vitamin E levels by supplementation with 500 I.U./kg of FO diet for 30 days significantly decreased lipid peroxidation and showed that in FO-fed mice, membrane peroxidation is inversely proportional to vitamin E content. However, due to a lower ratio of vitamin E and highly unsaturated fatty acids, FO-fed mouse membranes were more sensitive to pro-oxidant stimulus than were those from CO-fed mice. These findings illustrate the action of vitamin E against membrane lipid peroxidation and stress the importance of adequate supplementation of antioxidant with high omega-3 fatty acids intake. PMID- 2321493 TI - Accidental aspiration in children. PMID- 2321494 TI - Family practice approach to the prenatal visit. PMID- 2321495 TI - Progressive supranuclear palsy and dementia. PMID- 2321496 TI - Child abuse and neglect. PMID- 2321497 TI - Omeprazole: a new approach to gastric acid suppression. AB - Omeprazole, one of a new group of antisecretory drugs, is a substituted benzimidazole that does not exhibit the anticholinergic or histamine H2 antagonistic properties of drugs such as cimetidine. This agent suppresses gastric acid secretion by inhibiting the proton pump mechanism, thereby blocking the final step of acid secretion. Omeprazole is significantly more effective than the histamine H2 receptor antagonists in eliminating acid secretion; thus, it may be beneficial in patients who are resistant to these agents. Omeprazole is indicated for severe erosive esophagitis, gastroesophageal reflux disease that does not respond to H2 receptor antagonists, and hypersecretory diseases such as Zollinger-Ellison syndrome and systemic mastocytosis. Because of the theoretic risk of carcinogenesis, short-term therapy is recommended, although long-term therapy is required for hypersecretory diseases. PMID- 2321498 TI - PHS issues statement on postexposure zidovudine use. PMID- 2321499 TI - Value of immediate angioplasty after intravenous streptokinase in acute myocardial infarction. AB - To improve reperfusion, immediate percutaneous transluminal coronary angioplasty (PTCA) was considered after intravenous streptokinase (0.75 to 1.5 million U) was administered to 98 patients with acute myocardial infarction less than 4 hours after the onset of chest pain. Thirty-four culprit arteries were occluded (group A); 42 arteries were patent with residual stenosis of more than 70% (group B). Twenty-two patients had residual stenosis of less than 70% (group C); eight of these had severe disease of the remaining vessels. Group C patients were either treated conservatively or underwent bypass surgery. Immediate PTCA was attempted in 74 patients (32 in group A, 42 in group B) and was successful in 68 (92%). Emergency bypass surgery for acute occlusion after PTCA was required in two patients. Follow-up averaged 23 months (range, 16 to 47 months). Asymptomatic occlusion recurred in three patients. Restenosis occurred in five patients: four had early restenosis (one in group A, three in group B) and one had late restenosis (group B). These arteries were successfully redilated. Late reinfarction occurred in two patients. They were treated with intravenous urokinase and repeat PTCA. Elective bypass surgery was performed in three patients because of recurrent angina. They had severe three-vessel disease as revealed by control angiography. The mortality rate was 2.7% (two patients; one in group B had early reinfarction, and one patient in group A died suddenly after 17 months). Eighty-five percent of patients treated with PTCA alone remain free of symptoms. This approach has a high success rate and low morbidity and mortality rates. Long-term results are superior to thrombolysis alone. PMID- 2321500 TI - Long-term outcome of unsuccessful percutaneous transluminal coronary angioplasty. AB - We analyzed the long-term outcome of 198 patients after unsuccessful percutaneous transluminal coronary angioplasty. Forty-nine percent underwent emergency coronary artery bypass grafting surgery, 17% had elective bypass surgery, and 34% were treated medically. The in-hospital mortality rate was 4%, and myocardial infarction occurred in 36% of patients. Follow-up was completed in 100% of patients with a mean follow-up period of 35 +/- 22 months. Actuarial cardiac survival at 4 years was 97% in the emergency bypass surgery group, 100% in the elective bypass surgery group, and 86% in the medically treated group. Actuarial event-free survival (freedom from myocardial infarction, bypass surgery, coronary angioplasty, and cardiac death) at 4-year follow-up was 81% in 198 patients, 90% in the emergency bypass surgery group, 85% in the elective bypass surgery group, and 65% in the medically treated group. Results of multivariate analysis showed that emergency or elective bypass surgery after failed coronary angioplasty, normal or mildly impaired left ventricular function, and male sex were predictors of better outcome at 4 years. PMID- 2321501 TI - Percutaneous transluminal coronary angioplasty in silent ischemia. AB - The short- and long-term outcome of percutaneous transluminal coronary angioplasty were analyzed in 34 patients who had documented coronary artery disease without symptoms. Of the 34 patients, 33 had abnormal stress tests before angioplasty. Angioplasty was successful in 31 patients (91%). Follow-up was 100% for a mean period of 36 +/- 15 months. Follow-up exercise test was normal or improved in 29 of the 31 patients who had successful angioplasty. Follow-up catheterization was performed in 24 of the 31 patients (77%). Restenosis of the previously dilated segment was found in seven patients. Actuarial cardiac survival at 3 years was 100%. Freedom from myocardial infarction, bypass surgery, angioplasty for a new lesion, and death was 87%. We conclude that although the most effective treatment for silent ischemia remains to be determined, our data suggest that coronary angioplasty is a therapeutic option in these patients. PMID- 2321502 TI - In vivo infusion of oxygen free radical substrates causes myocardial systolic, but not diastolic dysfunction. AB - Contractile dysfunction of viable, previously ischemic stunned myocardium is thought to be due to reactive oxygen species generated during ischemia/reperfusion. Direct in vivo evidence that oxidants cause systolic or diastolic dysfunction of viable myocardium has, however, been lacking. We sought to determine whether in vivo exposure of canine myocardium to exogenously generated reactive oxygen species could--in the absence of myocardial ischemia or necrosis--"mimic" the depressed systolic contractile function, paradoxical contraction during early diastole, and prolonged diastolic relaxation time characteristic of stunned myocardium. Anesthetized open-chest dogs were randomly assigned to receive either (1) the free radical generating substrates xanthine oxidase + purine + iron-saturated transferrin or (2) saline, infused directly into an anterior coronary vein. Infusion of free radical substrates did not cause ischemia: regional myocardial blood flow and myocardial high-energy phosphate stores were normal in both groups. Furthermore, infusion of xanthine oxidase + purine + transferrin was not associated with histologic or electron microscopic evidence of myocyte injury or death in this model. Xanthine oxidase + purine + transferrin did, however, produce marked abnormalities in regional systolic contractile function; at 2 hours after the onset of infusion, segment shortening (assessed by sonomicrometry) in the perfused region of the heart averaged 62 +/- 5% of baseline, preinfusion values in animals infused with free radical substrates versus 113 +/- 8% of baseline values in saline-administered control dogs (p less than 0.004). This systolic dysfunction was effectively reversed by administration of the free radical scavenging agents superoxide dismutase + catalase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321503 TI - Serial evaluation of right ventricular dysfunction associated with acute inferior myocardial infarction. AB - Right ventricular (RV) function was evaluated serially by multigated blood pool imaging in 18 patients with RV dysfunction associated with acute inferior myocardial infarction. Radionuclide ventriculograms were performed on all patients within 18 hours of chest pain and again at 10 days. In addition, 15 of 18 patients had rest and exercise radionuclide ventriculograms at 3 months. The mean resting right ventricular ejection fractions (RVEF) at admission, 10 days, and 3 months in these patients was 31.8 +/- 12.6% (SD), 46.9 +/- 11.2% (p less than 0.05), and 44.5 +/- 10.2% (p less than 0.05), while the left ventricular ejection fractions were 55.9 +/- 10.6%, 57.9 +/- 13.3%, and 53.1 +/- 11.2% (p = ns). The 3-month exercise radionuclide ventriculogram demonstrated an increase in RVEF greater than 5% in 6 of 15 patients. In eight catheterized patients, neither the location nor the severity of coronary artery narrowing nor the presence of collaterals correlated with the RV exercise response. Improvement in RV function over a 10-day interval following acute inferior myocardial infarction suggests the presence of significant reversible right ventricular dysfunction during the acute phase. PMID- 2321504 TI - Prognostic significance of complete atrioventricular block in patients with acute inferior myocardial infarction with and without right ventricular involvement. AB - Data were obtained and analyzed in 243 patients with acute inferior myocardial infarction who were admitted to the coronary care unit during the years 1987 and 1988. One hundred and ninety-eight patients had no signs of right ventricular involvement (group I), whereas 45 patients had inferior myocardial infarction with right ventricular infarction (group II). Patients were divided into groups depending on the presence or absence of complete atrioventricular block during hospital stay (groups Ia and IIa without block and groups Ib and IIb with block). Selected clinical and laboratory variables were compared for each group. We found that patients with inferior myocardial infarction and complete atrioventricular block had significantly higher mortality rates only in the presence of right ventricular infarction: 41% mortality rate in group IIb versus 11% mortality rate in group Ib (p less than 0.05). Patients with right ventricular infarction but without complete atrioventricular block (group IIa) had a mortality rate similar to that found in patients with inferior myocardial infarction and no atrioventricular block (group Ia): 14% versus 11% (p = NS). In patients with inferior myocardial infarction without right ventricular involvement (group I), complete atrioventricular block did not influence survival: 14% mortality rate in group Ib versus 11% mortality rate in group Ia (p = NS). The excessively high mortality rate in patients who have inferior myocardial infarction with right ventricular involvement and complete atrioventricular block could be the consequence of greater infarct size, but the synergistic influence of right ventricular infarction and complete atrioventricular block could be the other factor that influences outcome. PMID- 2321505 TI - Exercise-induced impairment of diastolic time in patients with X syndrome. AB - Since an abnormal shortening of diastolic duration during exercise in the patients with coronary artery disease was demonstrated, time course of diastolic period (cardiac cycle minus electromechanical systole) calculated from polycardiographic recording has been assessed in patients with X syndrome and in normal age-matched subjects during supine ergometer exercise. All patients with X syndrome had positive exercise stress response (more than 0.1 mV of ST segment depression). Duration of diastole expressed as percent of cardiac cycle was significantly shorter at the intermediate steps and at the peak of exercise in patients with X syndrome compared with normal subjects (p less than 0.05). When the relationship between heart rate and diastolic time was examined, an inverse nonlinear regression was found both in normal subjects and in patients with X syndrome. The exercise values of diastolic time observed in patients with X syndrome were significantly shorter than those predicted as normal diastolic time heart rate relation. Thus the patients with X syndrome demonstrated abnormalities in the decrement of diastolic time with exercise. We hypothesized that this disproportionate shortening, by reducing subendocardial blood flow, might induce a worsening of ischemic response to exercise. PMID- 2321506 TI - Inhibition of platelet function during in vivo infusion of isosorbide mononitrates: relationship between plasma drug concentration and hemodynamic effects. AB - Isosorbide monitrates (IS-2-MN and IS-5-MN), hepatic metabolites of isosorbide dinitrate, inhibit platelet function in vitro very differently, with IS-2-MN being much more potent than IS-5-MN. To assess their antiplatelet properties in vivo and to compare time and dosage requirements, we infused both IS-2-MN and IS 5-MN for 30 minutes, on 2 separate days, into nine patients with stable coronary artery disease, at rates of 4 mg/hr (n = 4) and 8 mg/hr (n = 5). Two additional patients received IS-5-MN at 16 mg/hr. Platelet aggregation and thromboxane (TX) B2 generation in response to various agonists, drug plasma concentrations, and blood pressure were monitored throughout the study. A significant decrease in platelet aggregation and TXB2 production by adenosine diphosphate and adrenaline occurred in seven of nine patients receiving IS-2-MN and in 7 of 11 patients receiving IS-5-MN. Response was dose related, with more patients responding at 8 mg/hr to IS-2-MN (five of five) than to IS-5-MN (three of five), and was maximum at the end of the infusion time, corresponding to peak plasma levels. Patients responding to drug infusions with an inhibition of platelet function were characterized by a greater vascular responsiveness compared to nonresponders, since the decrease in systolic blood pressure (mean +/- SEM) was significantly greater in the former (15.4 +/- 3.2) than in the latter (2.5 +/- 2.1, p less than 0.05). Therefore both mononitrates, when administered at infusion rates between 8 and 16 mg/hr, are accompanied by a consistent inhibition of adenosine diphosphate and adrenaline-induced aggregation and TX generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321507 TI - Effect of acute hemodynamic decompensation on electrical inducibility of ventricular arrhythmias in patients with dilated cardiomyopathy and complex nonsustained ventricular arrhythmias. AB - In patients with dilated cardiomyopathy, hemodynamic decompensation has been postulated to increase vulnerability to reentrant ventricular arrhythmias. To test this hypothesis, we performed programmed ventricular stimulation with three extrastimuli on nine patients with dilated cardiomyopathy and asymptomatic complex ventricular arrhythmias during a period of acute hemodynamic decompensation; programmed ventricular stimulation was then repeated following hemodynamic improvement with nitroprusside. These patients did not have a history of documented or suspected sustained ventricular tachycardia or fibrillation. The mean left ventricular ejection fraction was 0.21 +/- 0.04 (range 0.15 to 0.26). In the baseline state, mean right atrial pressure was 8 +/- 4 mm Hg, pulmonary artery wedge pressure was 20 +/- 3 mm Hg, and cardiac index was 3.2 +/- 0.5 L/min/m2. Following acute hemodynamic decompensation, mean right atrial pressure increased to 16 +/- 5 mm Hg and pulmonary artery wedge pressure to 33 +/- 8 mm Hg; cardiac index decreased to 2.1 +/- 0.5 L/min/m2. In this decompensated state, programmed ventricular stimulation failed to induce sustained or nonsustained ventricular arrhythmias in any patient. Following nitroprusside administration (mean dose 1.5 +/- 1.1 micrograms/kg/min), there were significant decreases in mean right atrial pressure (11 +/- 3 mm Hg) and pulmonary artery wedge pressure (16 +/- 3 mm Hg), and a significant increase in cardiac index (3.1 +/- 1.1 L/min/m2) (p less than 0.05 for all values versus the decompensated state). In the improved hemodynamic state, programmed ventricular stimulation induced nonsustained ventricular tachycardia (six beats) in only one patient, and sustained arrhythmias in none.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321508 TI - Myocardial energetics and efficiency in patients with idiopathic cardiomyopathy: response to dobutamine and amrinone. AB - Nine consecutive patients having severe idiopathic dilated cardiomyopathy were studied for their response in ventricular function, coronary sinus blood flow and myocardial oxygen consumption, lactate extraction and efficiency following incremental doses of dobutamine, followed by the combination of dobutamine and the phosphodiesterase inhibitor amrinone. Results, presented as baseline and the response to the peak dose (15 micrograms/kg/min) of dobutamine and to the combination of dobutamine and amrinone (each at 15 micrograms/kg/min) (differences compared with baseline) were: wedge pressure decreased from 28 +/- 7 to 26 +/- 8 mm Hg (p = NS) and to 20 +/- 6 mm Hg (p less than 0.01); cardiac index rose from 1.47 +/- 0.44 L/min/m2 to 2.89 +/- 1.1 L/min/m2 (p less than 0.01) and to 3.64 +/- 1.05 L/min/m2 (p less than 0.001); myocardial oxygen consumption remained invariant (18 +/- 8, 17 +/- 5, and 19 +/- 5 ml/min) despite progressive increments in minute work from 2.96 +/- 1.1 to 6.98 +/- 3.9 kg - m/min (p less than 0.01) and to 9.38 +/- 4.3 kg - m/min (p less than 0.001); myocardial lactate extraction rose from 21 +/- 10% to 30 +/- 15% (p = NS) and to 35 +/- 10% with the addition of amrinone (p less than 0.01). No patient had net lactate efflux into the coronary sinus, and myocardial efficiency improved from 9.5 +/- 5% to 21.7 +/- 13.0% (p less than 0.01) and to 28.0 +/- 18.0% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321509 TI - Accuracy of mitral Doppler echocardiographic cardiac output determinations in adults. AB - The Doppler echocardiographic estimation of cardiac output at the mitral valve site is often underestimated in adults with slow heart rates because the mitral valve remains open in mid-diastole when flow is markedly reduced. Therefore we tested several approaches to this measurement in 17 adults with nonvalvular heart disease who had thermodilution catheters in the right side of the heart. Superior correlations with thermal output values were obtained by a new method that excludes mitral orifice measurements during mid-diastole when flow less than 10 cm/sec (r = 0.94) compared with the standard method (r = 0.89). Also, the new method resulted in significantly less underestimation of thermal cardiac output in patients with heart rates less than 70 beats/min (-10%) compared with the standard method (-34%). In addition, use of a constant maximal two-dimensional echocardiographic mitral orifice correction factor of 0.77 with the new method to account for variations in mitral valve orifice during the cardiac cycle, as opposed to 0.68 with the standard method, resulted in similar results as compared with determining individual correction factors from M-mode echoes. We conclude that: (1) the mitral orifice approach is accurate for measuring cardiac output in adult patients with nonvalvular heart disease; (2) a new method that excludes mid diastolic mitral orifice measurements is superior to the standard method; and (3) use of a constant two-dimensional echocardiographic mitral valve orifice correction factor obviates the need for M-mode echoes. PMID- 2321510 TI - Intrinsic heart rate in children and young adults: an index of sinus node function isolated from autonomic control. AB - Standard evaluation of children with sinus node (SN) dysfunction cannot distinguish abnormal autonomic tone from intrinsic SN disease. This distinction has potentially important therapeutic and prognostic implications. Intrinsic heart rate (IHR)--the peak heart rate (HR) measured during pharmacologic combined autonomic blockade--reflects intrinsic SN function. The purpose of this study was to evaluate the use of IHR--and its relationship with resting heart rate (RHR)- in distinguishing autonomic influence from intrinsic SN disease among children with SN dysfunction. IHR was determined in the electrophysiology laboratory using intravenous propranolol, 0.2 mg/kg, followed by intravenous atropine, 0.04 mg/kg; the peak HR recorded was the IHR. IHR was measured in two groups. Seven control subjects, defined as patients with normal noninvasive SN testing, had IHR mean of 128 +/- 24 beats/min; this was greater than RHR mean of 89 +/- 16 beats/min (p less than 0.01). Eight patients with abnormal noninvasive SN testing had IHR mean of 103 +/- 6 beats/min; this was greater than RHR mean of 71 +/- 9 beats/min (p less than 0.01). We therefore reached the following conclusions. (1) Among this particular group of patients with abnormal noninvasive SN testing, IHR was consistently in the normal range for age and greater than RHR, suggesting that excess vagal tone can play a significant role in the expression of SN dysfunction. (2) Among normal individuals, IHR is age-related, decreasing with advancing age. IHR greater than RHR suggests that vagal tone predominates in the normal resting state as the net increase in HR during combined autonomic blockade is due to blockade of vagally mediated chronotropic inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321511 TI - The scalar electrocardiogram of the orthotopic heart transplant recipient. AB - The 12-lead scalar electrocardiograms of heart transplant recipients were examined prior to hospital discharge (N = 191), and at 1 (N = 162), 2 (N = 97), and 3 years (N = 46) after transplantation. At the pre-discharge point, 46% had right bundle branch block (RBBB) QRS morphology (QRS duration greater than or equal to 120 msec: 20 patients, less than 120 msec: 67 patients). This finding tended to be manifest on the first day following transplantation; its prevalence remained constant over 3 years of follow up. Rejection, ischemic time, preoperative pulmonary vascular resistance, and donor age were not associated with the presence of RBBB morphology. A subgroup of 46 consecutive patients (21 with RBBB morphology) underwent right-sided heart catheterization and radionuclide angiography prior to discharge. RBBB morphology was not associated with any hemodynamic abnormality at catheterization. Based on the radionuclide study, RBBB morphology was associated with a greater left anterior oblique angle required for the best visual separation of the ventricles during acquisition of the study (angle of interventricular septal plane to sagittal plane: 69 +/- 11 versus 59 +/- 9 degrees; p = 0.019), and with the presence of right ventricular dysfunction (13 of 21 versus 6 of 25 patients; p = 0.009). The high prevalence of RBBB morphology in heart transplant recipients appears to be related to posterior rotation of the long axis of the heart in the transverse plane, probably resulting from the surgical technique, and to right ventricular dysfunction. PMID- 2321512 TI - Percutaneous left ventricular endomyocardial biopsy with angioscopic guidance in patients with dilated cardiomyopathy. PMID- 2321513 TI - Acute myocardial infarction complicating percutaneous aortic valvuloplasty successfully treated by percutaneous coronary angioplasty. PMID- 2321514 TI - Thrombolytic therapy in coronary ectasia and acute myocardial infarction. PMID- 2321515 TI - Intrapericardial "negative" cannon waves during atrioventricular dissociation in large pericardial effusion. PMID- 2321516 TI - Diagnostic implications of the echocardiographically demonstrated pericardial peel. PMID- 2321517 TI - Malignant lymphoma compressing the heart and causing acute left-sided heart failure. PMID- 2321518 TI - Echocardiographic recognition of tubercular submitral left ventricular aneurysm extending into left atrium. PMID- 2321519 TI - Diagnosis of infective endocarditis on a Starr-Edwards prosthesis by transesophageal echocardiography. PMID- 2321520 TI - Role of echocardiography in the diagnosis of cardiac lymphoma. PMID- 2321521 TI - Absent aortic valve in hypoplastic left heart syndrome. PMID- 2321522 TI - Complete heart block due to interleukin-2 therapy. PMID- 2321523 TI - Functional pulmonary atresia: color flow recognition and treatment with extracorporeal membrane oxygenation. PMID- 2321524 TI - Limitations of the exercise test as a screen for acute cardiac events in asymptomatic patients. PMID- 2321525 TI - Closed distribution of Clozaril begins despite protests from APhA. PMID- 2321526 TI - Clinical pharmacy services improve patient care and reduce costs. PMID- 2321527 TI - Traditional values, innovative practices: pharmacists who provide cognitive services. PMID- 2321529 TI - Professional status and pharmacist shortages. PMID- 2321528 TI - Rare diseases: identifying needs. Report of the National Commission on Orphan Diseases. PMID- 2321530 TI - Pharmacists, help save the world! PMID- 2321531 TI - Usefulness of the dipyridamole-Doppler test for diagnosis of coronary artery disease. AB - Two-dimensional and Doppler echocardiographic studies and a hemodynamic investigation were performed during dipyridamole testing in 42 subjects (13 control subjects and 29 patients with coronary artery disease [CAD]), to evaluate the ability of dipyridamole Doppler echocardiography in identifying patients with ischemic left ventricular dysfunction. In the control group, after dipyridamole infusion, Doppler-derived parameters increased significantly from baseline (p less than 0.001). In patients with CAD, peak flow velocity, flow velocity integral and stroke volume failed to increase after dipyridamole infusion (0.89 +/- 0.21 to 0.85 +/- 0.18 m/s, difference not significant; 14 +/- 3 to 12 +/- 4 cm, difference not significant, and 56 +/- 13 to 50 +/- 14 ml/beat, p less than 0.05, respectively). Heart rate, rate pressure product, systemic vascular resistance and mean right atrial pressure had similar variations in the 2 groups. Changes in the 3 Doppler-derived parameters are closely related to the variations of peak positive dP/dt, stroke volume (thermodilution) and left ventricular end diastolic pressure and are closely related to the coronary angiography jeopardy score and to the appearance of wall motion abnormalities. Thus, by combining Doppler and 2-dimensional echocardiography, dipyridamole-induced myocardial ischemia may be detected in a high percentage of CAD patients, providing a sensitive tool for identifying patients with high-risk coronary artery anatomy. PMID- 2321532 TI - Percutaneous transluminal coronary angioplasty after non-Q-wave acute myocardial infarction. AB - The value of percutaneous transluminal coronary angioplasty (PTCA) for ischemia after a non-Q-wave acute myocardial infarction (AMI) was assessed prospectively in 33 consecutive patients. In 30 patients the indication for the procedure was post-AMI angina and 3 patients underwent PTCA for silent ischemia. A total of 43 lesions were attempted at 63 +/- 94 days after the non-Q-wave AMI. Primary PTCA success was obtained in 30 (91%) patients and no major complications occurred. Angiographic evaluation was performed either for symptoms or for protocol (7 +/- 1 months after PTCA) in 28 (93%) of the 30 patients with successful PTCA, but 2 patients (7%) who were asymptomatic refused the repeat angiogram. Twenty (71%) had no restenosis and 8 (29%) had restenosis. Of these, 5 patients with restenosis underwent a successful repeat PTCA (6 +/- 1 months after the initial procedure). At the last clinical follow-up (17 +/- 8 months), 2 of the 30 (7%) patients successfully dilated presented with stable angina despite medical treatment, whereas the rest (93%) remained asymptomatic. During the study period no patient died, had an AMI or required coronary artery bypass grafting. Thus, selected patients with ischemia after a non-Q-wave AMI, a "high-risk population," can be effectively treated with PTCA with an initial success rate and angiographic restenosis rate similar to that of the general PTCA population and appear to have sustained symptomatic benefit remaining free of subsequent cardiac events. PMID- 2321533 TI - Doppler echocardiographic evaluation of left ventricular diastolic function after percutaneous transluminal coronary angioplasty for unstable angina pectoris or acute myocardial infarction. AB - The effect of percutaneous transluminal coronary angioplasty (PTCA) on left ventricular (LV) diastolic function has not been systematically investigated in patients treated for unstable angina or ischemia after acute myocardial infarction (AMI). To assess the relation between reduction of stenosis severity and improvement in diastolic function in this setting, 42 patients with either unstable angina (n = 22) or post-AMI ischemia (n = 20) were serially monitored by Doppler echocardiography 8 +/- 5 hours before and 2 +/- 1 days after PTCA. Doppler LV filling indexes included isovolumic relaxation time, mitral deceleration time, E/A peak velocity ratio and atrial filling fraction. Eighteen aged-matched control subjects served to establish normal values for comparison. Before PTCA, both groups exhibited abnormal diastolic function demonstrated by prolonged isovolumic relaxation time and mitral deceleration time, decreased E/A ratio and increased atrial filling fraction. After PTCA isovolumic relaxation time and deceleration time decreased 18 +/- 28 (p less than 0.005) and 33 +/- 43 ms (p less than 0.002) in the unstable angina group and 18 +/- 23 (p less than 0.003) and 14 +/- 34 ms (difference not significant), respectively, in the post AMI ischemia group. An increase in E/A ratio and a decrease in atrial filling fraction occurred in both groups; however, these changes were significant only in patients with post-AMI ischemia (+21%, p less than 0.03 and -11.4%, p less than 0.005, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321534 TI - Value of gadolinium-diethylene-triamine pentaacetic acid dynamics in magnetic resonance imaging of acute myocardial infarction with occluded and reperfused coronary arteries after thrombolysis. AB - The use of the paramagnetic contrast agent gadolinium-diethylene-triamine pentaacetic acid (DTPA) was evaluated in magnetic resonance imaging (MRI) of 18 patients with an acute myocardial infarction after thrombolysis. The patency of the infarct-related vessel was assessed by coronary angiography. At 58 +/- 9 hours after infarction MRI was performed before and after bolus injection of 0.1 mmol/kg gadolinium-DTPA. Myocardial signal intensities were measured using a circumferential profile. Normal and infarcted myocardium showed a maximum signal intensity enhancement of 35 and 66%, respectively. Signal intensity of infarcted relative to normal myocardium (I/N) increased from 1.06 +/- 0.16 before to a maximum of 1.39 +/- 0.13 after gadolinium-DTPA (p less than 0.001), whereas the contrast between normal myocardium and a pseudo-infarct region in 2 healthy volunteers did not change. Between patients with reperfused infarct-related vessels and occluded vessels without collaterals, maximum I/N did not differ. However, observing I/N as a function of time after injection of gadolinium-DTPA, the reperfusion group differed from the occlusion group on images acquired directly after injection (1.29 +/- 0.10 vs 1.14 +/- 0.05, p less than 0.02). Thus, gadolinium-DTPA enhanced the visualization of acute myocardial infarction on relatively longitudinal (T1)-weighted MR images and its dynamics seem of potential value for the noninvasive assessment of coronary artery reperfusion after thrombolysis. PMID- 2321535 TI - Role of two-dimensional echocardiography, pulsed, continuous wave color flow Doppler techniques in the assessment of ventricular septal rupture after myocardial infarction. AB - Two-dimensional echocardiography, pulsed and continuous wave Doppler techniques were used for the evaluation of 15 consecutive patients (9 men, 6 women; mean age 71 years, range 61 to 79) with ventricular septal rupture due to acute myocardial infarction (7 anterior, 8 posterior). Standard and modified off-axis 2 dimensional echocardiographic views from parasternal, apical and subcostal windows correctly identified this defect in 14 of the 15 patients. Pulsed Doppler echocardiography confirmed the presence of left-to-right-sided shunt by showing a high-velocity, aliased, systolic flow and a low-velocity diastolic flow in the right ventricle in 14 patients. Continuous wave Doppler echocardiography showed a high-velocity systolic and low-velocity diastolic flow signal of left-to-right shunt in 14 patients. Color flow Doppler imaging identified a left-to-right shunt in all 6 patients in whom it was performed. Doppler and 2-dimensional echocardiographic studies missed a small apical septal defect in 1 patient with anteroseptal myocardial infarction. Two-dimensional echocardiography correctly diagnosed right ventricular infarction in all 5 patients with posteroinferior infarction. Ventricular septal rupture and/or left-to-right-sided shunt was confirmed in all 15 patients by the following: surgical inspection in 11, necropsy in 3, left ventricular cineangiography in 5 and right-sided heart catheterization and oximetry data in 13 patients. Data indicate that 2 dimensional echocardiography correctly shows the precise location of septal rupture in most patients after acute myocardial infarction and allows assessment of left and right ventricular infarction and function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321536 TI - Transmural ventricular activation during consecutive cycles of sustained ventricular tachycardia associated with coronary artery disease. AB - Although computerized mapping has enabled the intraoperative delineation of global ventricular activation from a single complex of ventricular tachycardia (VT), beat-to-beat reproducibility of isochronic maps has not been defined. To determine the reliability of single-beat analysis, epicardial and transmural ventricular electrograms during 6 consecutive VT cycles were analyzed in 10 patients during intraoperative mapping of sustained monomorphic VT. Bipolar electrograms were recorded simultaneously using sock and needle electrodes from up to 96 epicardial and 156 transmural sites. In each patient, at each electrode site, local activation time, electrogram duration and morphology were compared over 6 consecutive beats. A total of 9,816 electrograms were analyzed. For each patient, the isochronic activation map during VT was reproducible. Mean beat-to beat variations in local epicardial and transmural activation times were only 1.7 +/- 1.7 and 2.04 +/- 1.9 ms, respectively (difference not significant). Moreover, electrogram duration did not vary significantly. Mean variations in epicardial and transmural electrogram durations were 2.1 +/- 1.8 and 1.4 +/- 1.9 ms, respectively (difference not significant). There were only 2 instances of 2:1 conduction failure; both occurred intramurally and adjacent to a site of VT origin. Thus, transmural ventricular activation during sustained monomorphic VT is reproducible regardless of electrode site or electrogram duration. These results demonstrate that analysis of a single beat of VT is a reliable and expedient method to delineate ventricular activation during intraoperative computerized mapping for the purpose of clinical decision-making in patients with sustained monomorphic VT. PMID- 2321537 TI - Use of intravenous adenosine in sinus rhythm as a diagnostic test for latent preexcitation. AB - In a proportion of patients with left free wall accessory connections, preexcitation is apparent only during atrial arrhythmias or atrial pacing (latent preexcitation). These patients may be at risk of a rapid ventricular response to atrial fibrillation despite the absence of preexcitation in sinus rhythm. The ability of intravenous adenosine to unmask latent preexcitation was evaluated in 22 patients with a history of documented supraventricular tachycardia and a normal electrocardiogram during sinus rhythm. Preexcitation was unmasked in response to adenosine in 4 patients: all 4 were shown to have latent preexcitation at electrophysiologic study. In 12 patients atrioventricular (AV) nodal conduction delay or block was induced without preexcitation after adenosine (first-degree AV block in 8, second-degree block in 4): at subsequent electrophysiologic study none of these patients was found to have latent preexcitation. Five patients had little or no PR prolongation in response to adenosine: of these, 2 were shown to have latent preexcitation at electrophysiologic study. Atrial fibrillation was induced in 1 patient and a narrow complex regular tachycardia in another after intravenous adenosine. Intravenous adenosine during sinus rhythm is capable of producing AV nodal conduction delay or block in 73% of patients with a history of supraventricular tachycardia: in these patients adenosine provides a diagnostic test that is both 100% sensitive and 100% specific for latent preexcitation. In those patients in whom adenosine does not produce AV conduction delay or block, further investigation is required to establish or refute the diagnosis of latent preexcitation. PMID- 2321539 TI - Rapid identification of the course of anomalous coronary arteries in adults: the "dot and eye" method. AB - It is often difficult to delineate the true course of anomalous coronary arteries by angiography because it only provides a 2-dimensional view of a complex 3 dimensional structure. The purpose of this study was to confirm morphologically the radiographic appearance of anomalous coronary arteries and to construct a protocol for rapid determination of their true course. Twenty-one adults who had anomalous origin of coronary arteries without other evidence of congenital heart disease were reviewed. Using an anatomically correct model of the heart, solder wire was placed in the pathologically described anomalous positions and radiographed. With this model the pathologically described courses could be easily recognized and separated radiographically. These courses were confirmed in the operating room in 2 patients and a rare anomaly of posterior origin of a coronary artery was also confirmed by autopsy. PMID- 2321538 TI - Frequency of acute myocardial infarction in valve repairs versus valve replacement for pure mitral regurgitation. AB - Three hundred thirty-five consecutive isolated mitral valve operations for mitral regurgitation in patients with no significant coronary artery disease were reviewed over a 26-month period for the presence of a perioperative acute myocardial infarction (AMI). Of 224 patients undergoing mitral valve repair 12 (5.4%) had electrocardiographic and cardiac enzyme evidence of perioperative AMI develop. Of 111 patients undergoing mitral valve replacement none had perioperative AMI develop as determined by electrocardiographic and enzyme criteria (p = 0.01). All 12 infarctions after valve repair involved the inferior wall by electrocardiographic or echocardiographic criteria. Although no patient had significant clinical difficulty in recovery, 7 of the 12 patients (58%) were left with Q waves upon hospital discharge. The etiology of the AMI is believed to be air emboli introduced at the time of testing valve competence during left ventricular insufflation under pressure. Changes in surgical technique may reduce or eliminate this complication. PMID- 2321540 TI - Doppler echocardiographic evaluation of left ventricular diastolic function in adolescents with diabetes mellitus. AB - Doppler echocardiograms of the mitral valve were recorded along with electrocardiograms and respirations from 20 diabetics and 16 normal subjects, all aged 10 to 15 years. E and A areas (the components of the total velocity-time integral in the early passive period of ventricular filling [E] and the late active period of atrial emptying [A], respectively), the peak E and A velocities (cm/s) and the 1/3 area fraction (or the proportion of filling in the first 1/3 of diastole) were measured. Each of the following was significantly greater for the normal subjects versus diabetic patients: peak E (96 +/- 14 vs 81 +/- 14 cm/s, p less than 0.005), E/total area (0.74 +/- 0.04 vs 0.69 +/- 0.06, p less than 0.005) and peak E/A velocity ratio (2.38 +/- 0.55 vs 1.92 +/- 0.55, p less than 0.05). The mean heart rates and ages were not significantly different for the 2 groups. The remaining parameters (peak A velocity, A/total area, E/A area, and 1/3 area fraction) were also not significantly different for the 2 groups. This study is the first to demonstrate diastolic dysfunction in pediatric patients with diabetes and may indicate abnormalities of ventricular relaxation or compliance in diabetes mellitus. PMID- 2321541 TI - Effects of caffeine on blood pressure response during exercise in normotensive healthy young men. AB - The possible combined effects of caffeine and exercise on blood pressure (BP) regulation were examined in 34 healthy, normotensive (BP less than 135/85 mm Hg) young men (mean age 27 +/- 3 years) in a placebo-controlled, double-blind crossover design. Each subject performed submaximal and symptom-limited maximal supine bicycle exercise 1 hour apart after ingestion of placebo or caffeine (3.3 mg/kg). Heart rate, BP, cardiac output and peripheral vascular resistance were compared for placebo and caffeine days. Postdrug baseline showed that caffeine increased systolic and diastolic BP and peripheral vascular resistance (p less than 0.001 for each) and decreased heart rate (p less than 0.01) but did not change stroke volume or cardiac output. BP and vascular resistance effects of caffeine remained during submaximal exercise resulting in an additive increase in BP while negative chronotropic effects of caffeine disappeared. At maximal exercise substantially more subjects (15 on caffeine vs 7 on placebo, p less than 0.02) had systolic BP greater than or equal to 230 mm Hg and/or greater than or equal to 100 mm Hg for diastolic BP. Plasma norepinephrine levels were not significantly different across days, but epinephrine was higher at maximal exercise and cortisol was increased post-drug and throughout maximal exercise on caffeine days. Data indicate that caffeine increases BP additively during submaximal exercise and may cause excessive BP responses at maximal exercise for some individuals. The pressor effects of caffeine appear to be due to increasing vascular resistance rather than cardiac output. PMID- 2321542 TI - Variation in the Reflotron method of cholesterol measurement. PMID- 2321543 TI - Angiographic evaluation of vasomotor properties of internal mammary arteries before and after coronary artery bypass grafting in men. PMID- 2321544 TI - Prevalence of anticardiolipin antibodies in coronary artery disease. PMID- 2321545 TI - Acute intervention during myocardial infarction in patients with prior coronary bypass surgery. PMID- 2321546 TI - Effects of verapamil on the anaerobic threshold and peak oxygen consumption in effort angina pectoris. PMID- 2321547 TI - Paradoxical increase in heart rate before conversion to sinus rhythm in patients with recent-onset atrial fibrillation. PMID- 2321548 TI - Atrioventricular septal defect and Ebstein's malformation. PMID- 2321549 TI - Effects of altered cardiac ventricular chamber size on the electrocardiogram and position of the heart. PMID- 2321550 TI - False-positive treadmill exercise tests due to computer signal averaging. PMID- 2321551 TI - Rapid method to determine the electrocardiographic frontal plane axis. PMID- 2321552 TI - Effect of sampling site on Doppler-derived right ventricular systolic time intervals. PMID- 2321553 TI - Blood rheology as a contributing factor in reduced coronary reserve in systemic hypertension. AB - The influence of blood fluidity on coronary reserve in patients with essential hypertension and normal coronary arteries was examined. The coronary reserve, expressed as the ratio of coronary vascular resistance under resting conditions to the coronary vascular resistance after administration of dipyridamole, was 4.1 +/- 1.5 in 10 normotensive patients with normal coronary arteries, whereas the mean value was only 2.4 +/- 0.8 in 35 hypertensive patients. When compared with the normotensive control group the 35 hypertensive patients had significantly higher levels of hematocrit (45.9 +/- 3.7 vs 42.3 +/- 3.6; p less than or equal to 0.01) and plasma viscosity (1.39 +/- 0.07 vs 1.32 +/- 0.06 mPas; p less than 0.01). Plasma fibrinogen (291 +/- 67 vs 251 +/- 25 mg/dl) and whole blood viscosity at a shear rate of 2 s-1 (7.77 +/- 1.1 vs 7.21 +/- 1.28 mPas) and at a high shear rate of 100 s-1 (4.23 +/- 0.57 vs 3.91 +/- 0.64 mPas) demonstrated a trend without statistical significance toward higher values in hypertensive patients. When the hypertensive group was further divided according to the coronary reserve (less than 2.5, severely impaired coronary reserve; greater than 2.5 less than 3.8, moderately impaired coronary reserve), the parameters of blood fluidity clearly correlated inversely with coronary reserve. This suggests a major importance of rheologic abnormalities on impaired coronary reserve in hypertensive patients. PMID- 2321554 TI - Direct vascular and myocardial effects of nisoldipine. AB - The effects of the dihydropyridine calcium antagonist nisoldipine on vascular smooth muscle and myocardium were investigated by brachial artery infusions and measurements of forearm blood flow and by intracoronary infusions and measurements of maximal rate of rise of left ventricular pressure (dP/dtmax). Brachial artery infusions (0.1 to 16 micrograms/min/1,000 ml tissue) in 10 patients with essential hypertension increased forearm blood flow and decreased calculated forearm vascular resistance dose dependently (maximal reduction of forearm vascular resistance 88%). A comparison with the vascular effects of verapamil indicated that the vasodilator potency of nisoldipine is approximately 40- to 50-fold greater in this model supporting similar results from in vitro experiments. Coronary artery infusions of nisoldipine (12, 24 and 48 micrograms over 3 minutes each) in 9 patients undergoing diagnostic left-sided cardiac catheterization did not change dP/dtmax. This lack of effect on left ventricular contractility was similar in patients with normal or impaired left ventricular function. Even though the coronary artery concentrations during the infusion are unknown, the highest intracoronary dose was comparable to the highest brachial artery infusion. Since the coronary vasculature has been found to be at least as sensitive to nisoldipine as the peripheral vasculature, it can be assumed that nisoldipine has no negative inotropic effect even in dosages that probably induced marked vasodilation. Thus, for nisoldipine and possibly other new dihydropyridine calcium antagonists, the concept of a dissociation between peripheral vasodilatation and direct myocardial effects also seems to apply to human circulation and the heart. PMID- 2321555 TI - Effect on the myocardial energy metabolism of angiotensin-converting enzyme inhibition in chronic heart failure. AB - There is substantial evidence that the failing heart is in an energy-depleted state. The imbalance between myocardial oxygen supply and demand might be the cause for adaptive metabolic changes seen in patients with severe chronic heart failure. By analyzing the lactate dehydrogenase (LDH) isoenzyme pattern, an increase of LDH5 and a decrease of LDH1 was seen in myocardium from patients with chronic heart failure. Additionally, the concentration of the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier was significantly elevated. After treatment with the angiotensin-converting enzyme inhibitor enalapril in 33 patients with chronic heart failure, LDH1 increased from 38.7 +/- 6.7 to 42.3 +/- 5.5 (p less than 0.005), paralleled by a decrease in LDH5 from 20.8 +/- 7.0 to 15.8 +/- 4.7 (p less than 0.001). The ADP/ATP carrier concentration also decreased significantly within the normal range. There was a good correlation between the hemodynamic data and the LDH isoenzyme pattern. The shift of the LDH isoenzyme pattern and the decrease of the ADP/ATP concentration can be taken as an indication for an improvement of the myocardial energy balance in chronic heart failure with angiotensin-converting enzyme inhibitor therapy. PMID- 2321556 TI - Germinal cell ectopism in the strepsirhine prosimian Galago crassicaudatus crassicaudatus. AB - The presence of germinal cells outside of the embryonal and fetal gonads of the strepsirhine prosimian Galago crassicaudatus crassicaudatus is described. Forty three embryos and fetuses from day 26 or 27 of gestational age to near term were studied: more than 90% possessed germinal cells in ectopic sites situated either far from (extragonadal ectopism) or close to the gonads (perigonadal ectopism). The first sites were the walls of the aorta and mesenteric artery, the stroma between the aorta and the cardinal vein, and the retroperitoneal neuroganglia. The second were the mesenchyme dorsal to the gonads and around the vestigia of the mesonephric glomeruli and tubules, and the rete ovarii and testis. The ectopic cells were generally present in conscpicuous numbers, in some animals being more numerous than in the gonads. Those situated far from the gonads underwent degeneration and decreased significantly in numbers during post embryonal stages of development, while the others remained numerous and functionally active up to near term. While the differentiation of the extragonadal germinal cells after day 60 of gestational age could not be studied due to technical difficulties, the XX and XY cells in perigonadal sites appeared to follow patterns of differentiation identical to those of their entopic counterparts. PMID- 2321557 TI - An investigation of lymphatic vessels in the feline dental pulp. AB - The existence of lymphatic vessels in the dental pulp has been a matter of continuing controversy. We have now used light microscopy to examine semithin transverse sections of perfusion-fixed incisors and canines in cats. Lymphatics were found in all the teeth studied. In most teeth they were present in the coronal, middle, and apical regions of the pulp; but in a few they were lacking coronally and in the middle. Within individual teeth, lymphatics were found in the subodontoblastic zone or more centrally in the pulp; but none were found in the odontoblast layer or in the pulp horns. Vessels located by light microscopy were subsequently examined by transmission electron microscopy. Their ultrastructural features were typical of lymphatics and included irregular, attenuated endothelium with adjacent cells joined in different ways. Occasional gaps connected the extracellular spaces with their lumens, and abluminal endothelial projections appeared to form open end bulbs. There was very little basement membrane, but anchoring filaments were found near the abluminal surface of the endothelium and near collagen fibrils. The total cross-sectional area of lymphatic vessels was measured in semithin sections and, with pulp area, increased from the coronal region to the middle. However, both areas decreased from the middle to the apical region suggesting either that lymph flows faster as it reaches the foramens of the apical delta or that some vessels leave the tooth through lateral root canals. Using the methods of light and transmission electron microscopy, therefore, we have shown that pulp lymphatic vessels exist. Questions remain, however, about their distribution within teeth, variations between teeth, and routes of exit from teeth. PMID- 2321558 TI - Flow cytometric DNA analysis of corneal epithelium. AB - We have modified an existing technique in order to perform DNA analysis by flow cytometry (FCM) of corneal epithelium from the mouse, rat, chicken, rabbit, and human. This protocol permitted an investigation of human corneal scrapings from several categories: normal, aphakic bullous keratopathy (ABK), keratoconus (KC), Fuch's dystrophy, edema, epithelial dysplasia, and lipid degeneration. No abnormal characteristic cell-kinetic profile was detected when averaged DNA histograms were compared statistically between the normal and either ABK, KC, edema, or Fuch's dystrophy groups. Abnormal DNA histograms were recorded for cell samples that were taken 1) from three individuals who had epithelial dysplasia and 2) from one individual diagnosed with lipid degeneration. The former condition was characterized by histograms that had a subpopulation of cells with an aneuploid amount of DNA or had higher than normal percentages of cells in the S and G2 + M phases of the cell cycle. Corneal cells from the patient who had lipid degeneration had an abnormally high percentage of cells in the G2 + M phases of the cell cycle. The availability of accurate DNA flow cytometric analysis of corneal epithelium allows further studies on this issue from both experimental and clinical situations. PMID- 2321559 TI - Ultrastructural morphometric study of efferent nerve terminals on murine bone marrow stromal cells, and the recognition of a novel anatomical unit: the "neuro reticular complex". AB - In order to extend our understanding of the role of nerve fibers in the structure and function of bone marrow stroma, we have examined nerve terminals, arterioles, and capillaries in femoral bone marrow tissues of 50 C57BL strain mice, using electron microscopy and morphometric methods. Within the adventitia of arterioles, a particular type of cell, termed periarterial adventitial (PAA) cell, is characterized by a thin veil-like cytoplasm which concentrically surrounds both nerves and arterioles. Nerve fibers containing both unmyelinated and myelinated axons are distributed mainly between the layers of PAA cells, but are found rarely on the sinus walls or within the hematopoietic parenchyma. Quantitatively, the efferent nerve terminals with many synaptic vesicles are distributed mainly beside arterial smooth muscle cells (Type I: 58.8%) or between the layers of PAA cells (Type III: 33.2%), and rarely in hematopoietic parenchyma (Type II: 5.3%) or on sinus walls (Type IV: 2.7%). In the case of Type II-IV nerve terminals, efferent (autonomic) nerves and bone marrow stromal cells which are connected by gap junctions (sinus adventitial reticular cells, intersinusoidal reticular cells, and PAA cells) appear to constitute a potential functional unit for signal conduction. We would like to propose a new term for this anatomical unit in marrow, the "neuro-reticular complex." PMID- 2321560 TI - Angiology of the brain of the baboon Papio ursinus, the vervet monkey Cercopithecus pygerithrus, and the bushbaby Galago senegalensis. AB - The investigation was undertaken to compare the blood supply and venous drainage of the brain of the baboon P. ursinus, the vervet monkey C. pygerithrus, and the bushbaby G. senegalensis with that of man, because these animals are extensively used as research models. The blood supply of the three primates was found to be similar in each case. Like man they have a complete circulus arteriosus; but they have a single anterior cerebral artery, whereas man has paired anterior cerebral arteries. The arterial supply to the cerebellum in the primates is similar to that in man, the main difference being a "common inferior cerebellar artery" which bifurcates to form the anterior inferior cerebellar and posterior inferior cerebellar arteries. In man, these arteries arise separately from the basilar artery and vertebral arteries, respectively. The dural venous drainage was also found to be similar in these primates but was far more extensive than in man. The primates have additional sinuses--the more important of these being the "basisphenoid sinus" and the petrosquamous sinus. The former drains the basilar sinus and is itself drained via the vertebral venous plexus and internal jugular vein. The latter drains via the petrosquamous foramen into the retromandibular vein. The petrosquamous sinus has a rostral extension which drains through the foramen ovale and two lateral and medial connecting sinuses which drain the cavernous and basilar sinuses, respectively. These sinuses are not found in man. PMID- 2321561 TI - Anatomical studies of the coronary system in elasmobranchs: I. Coronary arteries in lamnoid sharks. AB - A study of the anatomy of coronary arteries has been done in five shark species of the order Lamniformes: Isurus oxyrinchus, Isurus paucus, Lamna nasus, Alopias superciliosus, and Alopias vulpinus. The study, which included 26 specimens, was carried out with the injection-corrosion technique, obtaining internal casts of the main trunks and coronary arterial branches. The results have shown a high degree of constancy in the coronary patterns in all species and a number of general features common to all of them, except for Alopias vulpinus. In this species, a mesh-like ventricular pattern of intramyocardial vessels was found instead of subepicardial ventricular coronary branches with a definite pattern. It was also shown that there is a wide range of variation among the species regarding the relative importance of the dorsal and ventral coronary trunks. Thus, Isurus oxyrinchus showed a clear predominance of the ventral coronary trunk, whereas in Alopias superciliosus, most of the ventricle was supplied by branches derived from the dorsal coronary trunk. PMID- 2321562 TI - Ratio of actual to predicted weight as an alternative to a power-type weight height index (Benn index). AB - In 1971 Benn described a form of relative weight that can be calculated as the ratio of actual to predicted weight from the linear regression of weight on height in a population. He also showed how to compute the exponent for a power type weight-height index that would be approximately equivalent to this relative weight. Benn did not, however, recommended that this "Benn index" be used instead of relative weight. The properties of these two weight-height functions were investigated in data on 10,606 white men and women aged 18-74 y examined in the 1976-1980 Second National Health and Nutrition Examination Survey (NHANES II). Compared with the power-type index, relative weight was preferable in that it was easier to compute with current software packages, was invariant at standard weight-for-height, and offered more flexibility. The limitations shared by both functions are discussed. Neither function should be used uncritically. PMID- 2321563 TI - Use of total-body electrical conductivity for the assessment of body composition in middle-aged and elderly individuals. AB - Body composition was predicted for 114 middle-aged and elderly individuals aged 35-90 y by using total-body electrical conductivity (TOBEC), densitometry, and hydrometry. Highly significant correlations were achieved between the TOBEC Phase value and fat-free mass (FFM) determined by densitometry (FFMd) and hydrometry (FFMdw) with values ranging from 0.713 to 0.981. TOBEC predicted FFM (FFMT) was consistently higher than either FFMd or FFMdw for both men and women in all age groups. A theoretical calculation of percent body fat was performed with a three component model with body density, total body water, and bone mineral content. The recalculation of fat was used to estimate a new FFM (FFMnew). These calculations resulted in a decrease in fat and an increase in FFMnew. Because the TOBEC signal is unaffected by bone mineralization, FFMT may provide a more accurate estimation of body composition than do FFMd or FFMdw in this group of individuals. PMID- 2321564 TI - Twenty-four-hour energy expenditure and basal metabolic rate measured in a whole body indirect calorimeter in Gambian men. AB - By use of a respiration chamber, 24-hour energy expenditure (EE), diet-induced thermogenesis (DIT), and basal and sleeping EE were measured in 20 young rural Gambian men during the "hungry" season (weight, 60.8 +/- 1.4 kg) and in a group of 16 European men matched for body composition (weight, 66.9 +/- 1.9 kg). The 24 h EE was lower in Gambian than in European men (2047 +/- 46 vs 2635 +/- 74 kcal/d, p less than 0.001, respectively). Basal EE and sleeping EE were also lower in Gambian than in European men (1.05 +/- 0.02 vs 1.25 +/- 0.02 kcal/min and 1.0 +/- 0.02 vs 1.18 +/- 0.02 kcal/min, p less than 0.01, respectively). DIT was blunted in Gambian compared with European men (6.3 +/- 0.6% vs 12.1 +/- 0.5%, p less than 0.001 respectively). The net efficiency of walking was greater in Gambian than in European men (23.2 +/- 0.3% vs 20.1 +/- 0.4%, p less than 0.001, respectively). A low basal and sleeping EE, a reduced DIT, and a high work efficiency are important energy-sparing mechanisms in Gambian men, which allow them to cope with a marginal level of dietary intake during the hungry season. PMID- 2321565 TI - Skinfold thickness measurements in obese subjects. AB - To determine the accuracy of skinfold thickness measurements in body composition assessment, skinfold thicknesses, bioelectrical impedance, body density by underwater weighing, and total body water by deuterium dilution were determined in 105 healthy adults who varied widely in body fatness. Body fat ranged from 2.9% to 61.2% of body weight and a substantial number of obese subjects was included. The correlation between body fat calculated from skinfold equations and body fat measured by underwater weighing was in the same range as that between body fat estimated from impedance and underwater weighing. However, body fat calculated both from skinfold equations and bioelectrical impedance tended to be underestimated compared with body fat calculated from underwater weighing and total body water in the most obese subjects. In obese subjects it was not possible to measure significant numbers of skinfold thicknesses because of the inadequate size of the calipers. PMID- 2321566 TI - Energy metabolism of overweight women 1 mo and 1 y after an 8-wk slimming period. AB - Twenty-four hour energy expenditure (24EE) and spontaneous physical activity were measured in 13 overweight women before and at the end of an 8-wk slimming period. These measurements were repeated in 10 women 1 mo after the slimming period (1-mo follow-up) and in eight women 1 y after slimming (1-y follow-up). The weight loss achieved after 8 wk of slimming (8.7-9.9 kg) was maintained throughout the follow up periods; 24EE decreased during slimming from 9572 +/- 703 (means +/- SD) to 8060 +/- 471 kJ/d and increased after refeeding to 8379 +/- 739 kJ/d after 1 mo and to 8285 +/- 454 kJ/d after 1 y. On the basis of body weight, energy requirement (approximately 126 kJ.kg-1.d-1) did not change throughout the slimming and follow-up programs. Spontaneous physical activity, which had been lowered during slimming, tended to increase afterwards. No changes in metabolic efficiency seemed to occur or persist. PMID- 2321567 TI - Cholestyramine resin ameliorates chronic aminonucleoside nephrosis. AB - We chose to assess the role of cholesterol reduction in chronic aminonucleoside nephrosis by pharmacologically lowering serum cholesterol with cholestyramine. Two groups of rats were made nephrotic with a single intravenous dose of puromycin aminonucleoside (PA): one group (PA/resin) received 5% (w:w in diet) cholestyramine resin and the dietary control group (PA/cell) received 5% cellulose. Cholestyramine-treated rats demonstrated significant functional and histological protection. Recurrent proteinuria was significantly lower in PA/resin animals. Whole-kidney glomerular filtration rate in the PA/resin group was preserved at a level equivalent to normal age-matched control rats whereas the PA/cell group had a significantly lower value than did the normal animals. The extent of segmental glomerulosclerosis 24 wk after PA delivery was significantly lower in the PA/resin group. These results suggest a role for hyperlipidemia as one of the mechanisms involved in the pathogenesis of progressive glomerular disease. PMID- 2321568 TI - Glutamine transport by human intestinal basolateral membrane vesicle. AB - This study characterizes for the first time, by use of a well-validated technique, glutamine transport across human basolateral membrane vesicles. Glutamine transport represented uptake into an osmotically active intravesicular space without significant metabolism. Glutamine uptake was temperature- and pH dependent with maximal uptake at pH 7.5, and it was mediated by sodium-dependent and -independent processes. The initial rate of uptake was linear up to 20 s, as depicted by the formula gamma (nmol/mg protein) = 0.0009 X (s) - 0.0011 (r = 0.99). Kinetic analysis of glutamine uptake at concentrations between 0.01 and 0.3 mmol/L at 5 s under sodium and potassium gradients showed a maximal transport capacity (Vmax) of 0.39 +/- 0.04 and 0.21 +/- 0.02 nmol.mg protein-1.5 s-1 for sodium-dependent and -independent processes, respectively (p less than 0.01). Km values were 0.17 +/- 0.04 and 0.06 +/- 0.2 mmol/L, respectively (p less than 0.05). Glutamine uptake under the sodium-gradient condition was electrogenic whereas under the potassium-gradient it was electroneutral. Neutral amino acids inhibited both sodium-dependent and -independent processes. This study confirms and characterizes the presence of carrier-mediated glutamine uptake at the basolateral membranes of human enterocytes. PMID- 2321569 TI - Regulation of metabolism of retinol-binding protein by vitamin A status in children with biliary atresia. AB - Regulation of retinol-binding protein (RBP) by vitamin A status was studied in 43 children; 25 had biliary atresia and vitamin A deficiency, 15 had biliary atresia treated by vitamin A, and 9 control children had normal liver and vitamin A status. Vitamin A and RBP were assayed and the two forms of RBP, holo-RBP and apo RBP, were separated in both liver and plasma. No difference in liver RBP concentrations was found between the three groups; apo-RBP was the most abundant form. Plasma RBP concentrations and the ratio of retinol to RBP were lower for vitamin A-deficient than for vitamin A-treated children. Two models could be proposed: 1) a preferential secretion of holo-RBP with variations in RBP catabolism or synthesis in vitamin A-deficient liver and 2) a continuous secretion of RBP by the liver with a rapid clearance of plasma apo-RBP in vitamin A deficiency. PMID- 2321570 TI - Urinary hydroxyproline excretion and vitamin C status in healthy young men. AB - The relationship between ascorbic acid status and the urinary excretion of hydroxyproline was examined in 11 healthy male subjects fed an ascorbic acid deficient diet for 14 wk while in a metabolic unit. The diet provided 5 mg ascorbic acid/d and was supplemented with ascorbic acid to give intakes of 65 mg/d (2 wk), 5 mg/d (4 wk), 605 mg/d (3 wk), 5 mg/d (4 wk), and an average 375 mg/d (1 wk). The urinary excretion of hydroxyproline increased by an average of 16% and 30% after the first and second depletion periods, respectively, and decreased to baseline values after supplementation with normal or high doses of vitamin C. Significant (p less than 0.05) inverse correlations were found between urinary hydroxyproline and plasma, red cell, and leukocyte ascorbic acid. These results show that urinary hydroxyproline excretion increases during human vitamin C deficiency but that this effect is not strong enough to provide a reliable marker of mild vitamin C deficiency. PMID- 2321571 TI - Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women. AB - The effect of ascorbic acid on iron retention from a diet with predicted low iron bioavailability (containing minimal meat and ascorbic acid) was investigated in iron-depleted premenopausal women. Eleven women were depleted of storage iron (indicated by serum ferritin) through a combination of diet (5.0 mg Fe/2000 kcal for 67-88 d) and phlebotomy. They then consumed a diet containing 13.7 mg Fe/2000 kcal, supplemented with placebo or ascorbic acid three times daily (1500 mg total) with meals for 5.5 wk. Ascorbic acid improved apparent iron absorption (balance method) [38 +/- 2% (means +/- SEM) vs 27 +/- 2%]. Ascorbic acid also improved hemoglobin, erythrocyte protoporphyrins, and serum iron but not hematocrit, serum ferritin, iron-binding capacity, or transferrin saturation. In iron-depleted women consuming a diet with predicted poor iron availability, ascorbic acid supplementation enhanced body iron retention for 5.5 wk. PMID- 2321572 TI - Calcium absorption from kale. AB - Absorption of calcium from intrinsically labeled kale was measured in 11 normal women and compared in these same subjects with absorption of calcium from labeled milk. The average test load was 300 mg. Fractional calcium absorption from kale averaged 0.409 +/- 0.101 (means +/- SD) and from milk, 0.321 +/- 0.089 (P less than 0.025). In contrast with the poor absorption previously reported for spinach calcium, kale, a low-oxalate vegetable, exhibits excellent absorbability for its calcium. PMID- 2321573 TI - Copper status and urinary and salivary copper in young men at three levels of dietary copper. AB - Eleven young men were confined to a metabolic research unit for 90 d to determine the effect of the amount of dietary copper on copper nutriture. The study was divided into three metabolic periods (MP): 1) with an adequate-copper diet (1.68 mg/d) for 24 d, 2) with a low-copper diet (0.79 mg/d) for 42 d, and 3) with a high-copper diet (7.53 mg/d) for 24 d. Three indices of copper status, urinary copper, and salivary copper were determined at intervals throughout the study. Neither copper status, urinary copper, nor salivary copper differed among MPs. Sweat collections from three subjects suggested that losses of copper through sweat were very low and would not contribute significantly to copper balance. These results suggest that an amount of dietary copper slightly less than 0.8 mg/d is adequate to maintain copper status for greater than or equal to 42 d in normal, healthy men and that neither urinary nor salivary copper is affected by the amount of Cu in the diet. PMID- 2321575 TI - Dietary patterns, gastrointestinal complaints, and nutrition knowledge of recreational triathletes. AB - Dietary habits, nutrition knowledge, and gastrointestinal complaints were evaluated in 21 female and 50 male triathletes; 30 completed hemoccult slides to determine the frequency of gastrointestinal bleeding. Triathletes trained 11 h/wk with weekly distances of 5.3, 116.5, and 40.9 km for swimming, biking, and running, respectively. Mean daily energy intake averaged 9058 and 11,591 kJ for women and men, respectively; 53.8% of the energy was from carbohydrates. Mean intakes of vitamins and most minerals exceeded the Recommended Dietary Allowances (RDAs), but many had intakes below RDAs for some nutrients; greater than 60% had low zinc and copper intakes. Because 39% took a daily multivitamin-mineral supplement, some had intakes 200-600% above the RDA. Although there were notable misconceptions about nutrition, nutrition knowledge was high. Upper gastrointestinal complaints, reported by 50%, included bloating and abdominal gas; the incidence of positive hemoccult slides was 27%. The relation among performance, dietary patterns, nutrition knowledge, and gastrointestinal function remains to be established. PMID- 2321574 TI - A positive association between maternal serum zinc concentration and birth weight. AB - A study was conducted on a cohort of 476 women (364 black, 112 white), who attended the Jefferson County Health Department clinic for their prenatal care, to ascertain the relationship between maternal serum zinc concentration measured early in pregnancy and birth weight. For all subjects maternal serum zinc was significantly related to birth weight after various independent determinants of birth weight were controlled for. The data in this study indicate a threshold for maternal serum zinc concentration below which the prevalence of low birth weight increases significantly. Pregnant women who had serum zinc concentrations in the lowest quartile had significantly higher prevalence of low birth weight than did those mothers who had serum zinc concentrations in the upper three quartiles during pregnancy. These findings suggest that maternal serum zinc concentration measured early in pregnancy could be used to identify those women at higher risk of giving birth to a low-birth-weight infant. PMID- 2321576 TI - Soy formulas are not hypoallergenic. PMID- 2321577 TI - Ovarian carcinomas with transitional cell carcinoma pattern. AB - The authors report 88 cases of ovarian carcinoma containing areas of transitional cell carcinoma (TCC). The tumors were found in women 28-76 years old (mean, 51 years). Fifteen patients presented with stage II, 59 with stage III, and 14 with stage IV disease. Ten neoplasms were composed of only TCC, 48 were predominantly TCC, and 30 had foci of TCC but the predominant component was serous, endometrioid, undifferentiated, or unclassified adenocarcinoma. After the primary resection of the neoplasm, 76 patients received chemotherapy, 4 received chemotherapy and radiotherapy, and 5 received radiotherapy only; 2 refused further treatment and 1 patient died immediately after the first operation. Estimated five-year survival rates were 37% for the entire group and 41% for those who received chemotherapy. Favorable prognostic indicators, statistically significant, were low clinical stage, predominant TCC in the primary tumor, and a negative second-look operation. Other prognostic indicators were the amount of residual tumor after the first operation and tumor differentiation. When the primary neoplasm was predominantly TCC, another prognostic indicator was the type of carcinoma present in the metastases. Five-year follow-up shows that 56% of the patients whose metastases were predominantly TCC have no evidence of disease, whereas only 7% of the patients whose metastases are predominantly non-TCC are disease-free. The authors' study indicates that ovarian carcinomas containing predominant TCC pattern have an excellent response to different chemotherapy regimens. Tumor recurrences and lack of response to chemotherapy are often associated with a change in the histologic appearance of the metastatic lesion. PMID- 2321578 TI - Prostatic adenocarcinoma. Evaluation of immunoreactivity to monoclonal antibody B72.3. AB - Monoclonal antibody B72.3 reacts with a tumor-associated glycoprotein designated TAG-72 that is expressed in many adenocarcinomas but not in normal tissues. The authors evaluated the immunoreactivity of B72.3 to benign, hyperplastic prostate, and to primary adenocarcinoma of the prostate to determine the frequency of TAG 72 production by benign and malignant prostatic epithelium. Focal cytoplasmic staining of gland cells was seen in 19 of 20 cases of glandular hyperplasia, and weak, homogeneous staining of secretions was seen in five cases. In contrast, 27 of the 35 (77%) adenocarcinomas studied showed at least focal intense staining of secretions, and 30 (86%) of the tumors showed some cytoplasmic immunostaining with B72.3. Positive staining occurred in all of the well-differentiated adenocarcinomas (100%) but was seen less often in moderately differentiated (82%) and poorly differentiated adenocarcinomas (58%). Because benign gland cells may express the TAG-72 antigen, immunohistochemistry results must be interpreted with caution and with regard to the overall morphologic pattern. Nonetheless, a positive B72.3 immunostain may be useful in identifying adenocarcinoma of the prostate, especially when an intense luminal reaction is found. A negative stain does not exclude the presence of adenocarcinoma, however. PMID- 2321579 TI - Nuclear DNA content as a prognostic factor in T1-2N0 breast cancer. AB - One hundred fifteen patients with postsurgical stage T1-2N0 breast cancer with the minimum follow-up of 22 years and from a defined population were studied to find reliable prognostic factors predicting long-term survival rate. The 30-year survival rate corrected for intercurrent deaths was 75%, and no deaths of breast cancer occurred after the nineteenth year of follow-up. The 30-year crude survival rate was only 28%, indicating that the great majority of these patients ultimately die of other causes than breast cancer. The nuclear DNA content could be determined by flow cytometry in 95 of the 115 cases, and 52 (55%) of them were nondiploid. DNA ploidy (diploid vs. nondiploid, P = 0.11) did not have a significant influence on long-term survival rate, but cancers with the DNA index less than 1.2 had more favorable prognosis in a univariate analysis than those with the DNA index more than 1.2 (P = 0.02). The most important independent prognostic factor in Cox's multivariate analysis was the presence of lymphatic vessel invasion of cancer cells (P less than 0.001). Several other factors, including histologic grade and type, extent of necrosis, type of tumor margin, age at diagnosis, and primary tumor size could be shown to be of prognostic value in univariate and/or multivariate analyses. PMID- 2321580 TI - Diagnostic yield from 231 autopsies in a community hospital. AB - Autopsy reports of 231 adult autopsies were examined for clinically unexpected diagnoses. Analysis of data showed that 97 of 188 autopsy diagnoses were clinically unexpected. The diagnosis of pulmonary embolism was clinically the most frequently missed diagnosis relative to its actual occurrence. Also noted was that the proportion of cases with unexpected diagnoses increased from 1983 to 1987. PMID- 2321581 TI - Immunophenotyping of acute leukemias using paraffin-embedded tissue sections. AB - In a study of 55 patients with either acute lymphoid leukemia (ALL; 25 cases) or acute myeloid leukemia (AML; 30 cases), paraffin-embedded bone marrow particle sections were examined with a panel of monoclonal and polyclonal antibodies reactive toward lymphoid and myeloid-associated antigens, using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. All cases were previously classified according to the French-American-British (FAB) Co-operative Group, and cases of ALL were immunophenotyped by flow cytometry. Results indicated that myeloid-associated antibodies (Mac 387, KP 1 [CD68], antielastase, antilactoferrin, and antilysozyme) did not react with any case of ALL, M1-AML, or M6-AML, whereas at least one of these antibodies reacted with 20 of 21 (95%) cases of M2, M3, M4, and M5-AML. Anti-glycophorin C marked cases of M6-AML, whereas anti-CD3 labeled T-cell ALL. None of the antibodies tested specifically identified cases of B-cell ALL. The authors conclude that use of a selected panel of antibodies on paraffin-embedded bone marrow particle sections may be of value in the diagnosis and immunophenotypic classification of many cases of acute leukemias. PMID- 2321583 TI - von Willebrand's variant (type II Buffalo). Thrombocytopenia after desmopressin but absence of in vitro hypersensitivity to ristocetin. AB - Von Willebrand's disease is categorized into types and subtypes based on multimeric analysis of plasma von Willebrand's factor. Such categorization is of value because both the mode of inheritance and the choice of therapeutic material differ between subtypes. The Type IIB variant is characterized by hypersensitivity in vitro to ristocetin and thrombocytopenia after administration of desmopressin (DDAVP). Hypersensitivity to ristocetin has also been described in Type I variants but without thrombocytopenia after DDAVP. This report describes a new Type II variant characterized by the converse situation, absence of hypersensitivity to ristocetin in vitro but transient thrombocytopenia after intravenous administration of DDAVP. PMID- 2321582 TI - Experimental murine invasive pulmonary aspergillosis. AB - A new model of invasive pulmonary aspergillosis (IPA) was developed in immunosuppressed mice. Intranasal route of inoculation was used to deliver predictable numbers of Aspergillus flavus conidia. The LD50 was determined to be 2.7 X 10(2) viable conidia, and a combination of quantitative culture and determination of chitin content was shown to best measure the progression of pulmonary disease. The evolution of IPA in these mice conformed with what has been reported in human cases of aspergillosis; both histopathology of the pulmonary lesions and dissemination pattern resembled their human counterparts. The authors hope to use this model to study virulence mechanisms of Aspergillus and novel therapeutic methods. PMID- 2321584 TI - Abnormalities of leukocyte histograms resulting from microorganisms. AB - The authors report a series of 13 patients seen in their laboratory during October 1985 to August 1988 in which the presence of bacterial, fungal, or malarial parasites visible on peripheral smear was correlated with an abnormal leukocyte histogram. Samples submitted for complete blood count and differential counts were analyzed with Coulter S-Plus VI (seven specimens) or S-Plus STKR (six specimens) instrumentation. Organisms visualized on the Wright-stained peripheral smears included Histoplasma capsulatum (two), Candida sp. (four), Plasmodium sp. (three), and Staphylococcus sp. (four). Two patients had a diagnosis of acquired immune deficiency syndrome (AIDS); intravascular catheters were present in five other patients. In all cases the leukocyte histograms were abnormal. The instrument flagged abnormalities of the R1 region in four patients and multiple regions in nine patients. Similar flags were produced by the in vitro addition of bacteria or fungi to whole blood. These studies document that the presence of microorganisms in the peripheral blood can result in spurious white blood cell (WBC) counts or electronic differentials. The authors' findings indicate that the possibility of circulating organisms should be considered when abnormal WBC flags are detected with Coulter instrumentation. PMID- 2321585 TI - The impact of screening a heterogeneous donor population for alanine aminotransferase and hepatitis B core antibody. Experience at a large southern California hospital. AB - To reduce the transmission of non-A, non-B (NANB) hepatitis, the American Association of Blood Banks (AABB) has recommended that donors be screened for elevated levels of alanine aminotransferase (ALT) and for the presence of antibody to hepatitis B core antigen (anti-HBc). In this survey of 5,336 donors, the authors report the impact of using both of these surrogate tests on a heterogeneous donor population that was composed of white, black, Hispanic, and Asian donors. Hispanic and male donors had relatively high ALT levels, and black and Asian donors had a higher prevalence of anti-HBc than their respective counterparts. The overall impact of using both surrogate tests resulted in a discard rate of 12.1% with a disproportionately high percentage of Hispanic and male donors excluded because of ALT testing and black and Asian donors because of anti-HBc testing. It appears that surrogate testing has a much greater impact on blood collection facilities that rely considerably on Hispanic, Asian, black, or male donors than those that largely draw white or female donors. PMID- 2321586 TI - Immunophenotypic analysis of cells isolated from bone marrow biopsies in patients with failed bone marrow aspiration ('dry tap'). AB - A method for the immunophenotypic analysis of bone marrow cells in cases of failed bone marrow aspiration is described. Cell suspensions are obtained by mechanical disaggregation of bone marrow core biopsies. The isolated cells are stained with the appropriate antibodies and analyzed by flow cytometry. The usefulness of the method is illustrated by presenting immunophenotypic data obtained in eight consecutive cases accessioned by the authors' laboratory. The method is simple and reproducible. It allows for parallel morphologic examination with Romanovski-type stains and is capable of generating multivariate, quantitative, immunophenotypic data useful in the diagnosis of leukemia and lymphoma. PMID- 2321587 TI - Ristocetin-induced platelet aggregate formation and adherence to the probe of an impedance aggregometer. AB - The examination of the interaction between ristocetin and platelets generally is performed in an optical aggregometer where aggregate formation is detected by a change in turbidity. Ristocetin also will induce conductivity changes in an impedance aggregometer with either fresh whole blood or fresh platelet-rich plasma due to aggregate attachment to the electrical probe. Formaldehyde-fixed platelets, however, do not attach, and although fresh platelets agglutinate at extremes of pH, probe adhesion does not occur unless the pH is within a certain range. Incubation of platelet preparations with neuraminidase, colchicine, or cytochalasin-b affects neither aggregate formation nor probe adherence. Incubation of platelet preparations with a fibronectin tetrapeptide inhibitor eliminates aggregate formation in response to collagen but is without effect on ristocetin-induced attachment of aggregates to the impedance probe. It is suggested that the ability of platelet aggregates to attach to an impedance probe in response to ristocetin is dependent on additional aspects of the functional integrity of platelet preparations and that these changes required for probe adherence may have in vivo significance. PMID- 2321588 TI - Plasmacytoid T-cells in a reactive lymph node. Detection by flow cytometry? AB - Plasmacytoid T-cells (PTCs) are a histologically recognized component of some reactive nodes. To the best of the authors' knowledge, plasmacytoid T-cells have never been recognized as a distinct cell population in a reactive lymph node using cell suspension flow cytometric studies. The authors here report a case of reactive lymph node hyperplasia in which prominent aggregates of PTCs were present and a distinct cell population with an immunophenotype characteristic of PTCs was identified by flow cytometry. Aside from the recognition of PTCs, this observation is important so that cell suspensions showing a distinct population of PTCs with an "aberrant" T-cell phenotype are not misinterpreted as providing evidence for a T-cell neoplasm. PMID- 2321589 TI - Spurious automated leukopenia due to in vitro granulocyte aggregation. AB - A patient with spurious automated leukopenia secondary to in vitro aggregation of neutrophils is evaluated. The primary importance of this transient phenomenon is the potential generation of unnecessary clinical investigation and diagnostic expense. The cause of this phenomenon is not related to time, temperature, or type of anticoagulant. The true leukocyte count is obtained easily by diluted manual leukocyte counts. Presence of granulocyte aggregates on anticoagulated blood smears should suggest spurious leukopenia, and smears of anticoagulated blood should be examined in patients with unexplained leukopenia. PMID- 2321590 TI - Giant forms of Blastomyces dermatitidis in the pulmonary lesions of blastomycosis. Potential confusion with Coccidioides immitis. AB - Typical yeast-phase cells of Blastomyces dermatitidis have a characteristic appearance in tissue sections. Fungal morphologic variation occurs infrequently in the lesions of blastomycosis, yet it can complicate the differential diagnosis, particularly if fresh tissue is not available for microbiologic culture. The authors report a case of pulmonary blastomycosis, confirmed by culture and direct immunofluorescence, in which some of the yeast-like cells were abnormally large. These giant yeast-like cells exceeded the size range accepted for the tissue forms of B. dermatitidis; therefore, coccidioidomycosis was considered initially in the differential diagnosis. Otherwise characteristic morphologic features of these cells, in particular multinucleation and the production of broad-based blastoconidia, helped resolve the differential diagnosis. The diagnosis can be confirmed by direct immunofluorescence or microbiologic culture. PMID- 2321591 TI - Type IV Ehlers-Danlos syndrome presenting as sudden infant death. AB - A previously healthy 5-month-old female infant presented with sudden death due to spontaneous subarachnoid hemorrhage associated with minor multifocal visceral hemorrhages. The clinical diagnosis had been sudden infant death syndrome. Although the family history was noncontributory and other features of type IV Ehlers-Danlos syndrome (EDS) were absent, the pattern of hemorrhage was consistent with this type of connective tissue disorder. The diagnosis was confirmed after postmortem analysis of skin and aorta showed less than 5% type III collagen (normal greater than 15%). Extensive literature review failed to find any other reported cases of sudden death in infancy due to intracranial hemorrhage in patients with previously unsuspected type IV EDS. The authors suggest that collagen analysis should be performed in cases of unexplained multifocal spontaneous hemorrhage in infancy so that this rare diagnosis will not be missed. PMID- 2321592 TI - Possible association of acute inflammatory exudate in chorioamnionitis and amniotic squamous metaplasia. AB - Reported is a case of placental chorioamnionitis in which a dramatic absence of focal inflammatory response is observed in areas of local squamous metaplasia of the amnion. The authors do not think this observation has been reported in the literature. They describe their search to find a repeat occurrence and discuss possible implications of this finding. PMID- 2321593 TI - Signet-ring squamous cell carcinoma of the pyriform sinus. PMID- 2321594 TI - An American Board of Orthodontics case report. AB - This case report describes an adult patient with a bilateral Class II malocclusion and an extremely deep overbite. The patient was treated without extraction to the standards of the American Board of Orthodontics. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirements for the certification process conducted by the Board.] PMID- 2321595 TI - Measurement of intraoral muscle forces during functional exercises. AB - Measurements of intraoral muscle force with foil strain gauges, load cells, and pressure transducers bonded to a Tru-Tain stent and to a lip bumper appliance were tested by means of seven functional exercises in five adult subjects over a 5-day interval. The measuring devices and the functional exercises were tested for replicability and validity. Results showed that the pressure transducer was the superior measuring device with respect to size, sensitivity, thermal compensation, factory uniformity, replicability, and validity. The device most susceptible to error, on the basis of these factors, was the foil strain gauge. Of the seven functional exercises used, the pronunciation of the words "phone," "mom," and "church" and the exercise of swallowing were replicable over time. The other three exercises--chewing gum, sucking, and blowing on a straw--were determined to be unreliable in terms of replicability over time. Overall pressure values recorded were significantly higher than in previous reports. Pressure values were higher for the Tru-Tain stent than for the lip bumper. PMID- 2321596 TI - Changes in power spectrum of electromyograms of masseter and anterior temporal muscles during functional appliance therapy in children. AB - This study applied frequency analysis to compare changes in the power spectrum density functions of surface electromyograms obtained from the paired masseter and anterior temporal muscles during therapy with three types of functional appliances, namely the Bionator, modified Frankel type I, and Frankel type III. Eighteen children were divided into three groups receiving either Bionator, Frankel type I, or Frankel type III therapy; a fourth group consisting of six children who received no therapy served as control. Before and after 3, 6, and 12 months of therapy, each child performed maximum voluntary isometric clenches in the position of maximum intercuspation. The mean frequency of the power spectrum was the variable studied. Children treated with the Bionator and Frankel type I appliances showed greater changes in mean frequency than those treated with the Frankel type III appliance. Although the muscles of untreated children also showed shifts of mean frequency to lower frequency values as a function of time, there was a greater downward shift of mean frequency in those treated with functional appliances. The downward shifts might have been associated with changes in muscle fiber lengths and/or recruitment patterns as a result of both treatment and normal growth. PMID- 2321597 TI - Facial morphology and malocclusions. AB - The aim of this study was to determine whether sagittal and vertical aberrations in intermaxillary incisal tooth and jaw relationships were reflected in facial morphology. One hundred seventy-two children (79 girls and 93 boys), 12 to 14 years of age, were selected from the Orthodontic Department, University of Giessen. Pretreatment profile and frontal facial photographs as well as profile roentgenograms in centric occlusion for each child were made. The method consisted of (1) a personal appraisal of the existing incisal tooth and jaw relationship by visual inspection of facial photographs, (2) a validity assessment of these personal appraisals, and (3) a comparison of linear and angular measurements made from facial photographs and from lateral headfilms. The result of this investigation revealed that a large overjet and a Class II, Division 2 incisal tooth relationship were most often reflected in the face. A Class III incisal tooth relationship and an open bite, however, were difficult to detect. Sagittal maxillary and mandibular positions could only occasionally be determined on the basis of facial appearance, while a Class II jaw base relationship (large ANB angle) could easily be seen. The vertical jaw relationship (mandibular plane angle and anterior facial height index) could be determined with relatively high precision. When the measurements from the facial photographs were compared with those from the lateral headfilms, moderate to high correlations were found between skeletal and soft tissue readings: ANB angle (r = +0.63), mandibular plane angle (r = +0.93), and anterior facial height index (r = +0.86). It was concluded that sagittal and vertical dental and skeletal intermaxillary malrelationships were only partly reflected in the face. PMID- 2321598 TI - A long-term study of the relationship of third molars to changes in the mandibular dental arch. AB - The purpose of this study is to determine the relationship of third molars to changes in the mandibular dental arch. The sample for this study consisted of four groups and subgroups. The groups consisted of premolar extraction treated, nonextraction treated with initial generalized spacing, nonextraction treated, and serial extraction untreated subjects. The subgroups were divided into persons who had mandibular third molars that were either impacted, erupted into function, congenitally absent, or extracted at least 10 years before postretention records. The mean postretention time interval was 13 years, with a range of 10 to 28 years. The mean postretention age was 28 years 6 months, with a range of 18 years 6 months to 39 years 4 months. Two-way analysis of variance with repeated measures was used to compare the changes over time (before treatment, at end of active treatment, and after retention) of groups and third molar subgroups. With time, mandibular incisor irregularity increased while arch length and intercanine width decreased. The eruption patterns of mandibular incisors and first molars were similarly dispersed in all groups studied. The findings between the subgroups in which mandibular third molars were impacted, erupted into function, congenitally absent, or extracted 10 years before postretention records revealed no significant differences between any of the subgroups for the parameters studied. No significant differences in mandibular growth were found between the third molar subgroups; this suggests that persons with third molars erupted into satisfactory function do not have a significantly different mandibular growth pattern than those whose third molars are impacted or congenitally missing. In the majority of cases some degree of mandibular incisor crowding took place after retention, but this change was not significantly different between third molar subgroups. This finding suggests that the recommendation for mandibular third molar removal with the objective of alleviating or preventing mandibular incisor irregularity may not be justified. PMID- 2321599 TI - Comment reference in intrabracket space and intrabracket distance article. PMID- 2321600 TI - The extraction/nonextraction dilemma. PMID- 2321601 TI - Response to Dr. Johnston's viewpoint. PMID- 2321602 TI - Factors associated with orthodontic patient compliance with intraoral elastic and headgear wear. AB - Factors related to compliance with the wearing of headgear and intraoral elastics were explored in a sample of 100 university clinic orthodontic patients. Data were gathered by means of a questionnaire that comprised items presumed to be associated with orthodontic compliance. These items were not patient characteristics, but variables of beliefs, attitudes, perceptions, and reasons thought to be associated with compliance. The 58 questions were reduced through alpha factor analysis and the imposition of a coefficient alpha restriction to 12 factors. These 12 factors were named according to the questions they comprised. To assess whether these factors were indeed related to compliance, correlation coefficients were calculated between the factor scores (independent variables) and the criterion of compliance with headgear and elastics (dependent variable). Compliance was rated on a three-point scale. Four factors were found to be weakly, though significantly, correlated with compliance. These factors were combinations of personality type, negative motives (pain, inconvenience, and dysfunction), and positive motives (general health awareness, specific dental knowledge, and personal oral embarrassment). The findings were compared with existing theories of patient behavior. PMID- 2321603 TI - Legal aspects of orthodontic practice: risk management concepts. Protecting your personal assets. PMID- 2321604 TI - Ambulatory Pediatric Association. Program and abstracts. Thirtieth annual meeting. May 7-11, 1990, Anaheim, CA. PMID- 2321605 TI - Management of coin ingestion. PMID- 2321606 TI - Pediatric coin ingestion. PMID- 2321607 TI - Beta-hemolytic non-group A streptococci and pharyngitis. PMID- 2321608 TI - Poliovirus vaccine policy. PMID- 2321609 TI - Management of diabetes in pediatric resident clinics. PMID- 2321610 TI - Bacterial meningitis in older children. AB - A review was performed of 25 cases of bacterial meningitis in previously healthy children aged 6 years or older during a 10-year period. The rate of infection in this age group relative to all cases of pediatric bacterial meningitis was 4%. Pathogens included Haemophilus influenzae type b in 10 cases (40%), Neisseria meningitidis in 9 cases (36%), and Streptococcus pneumoniae in 6 cases (24%). Physical findings revealed 21 patients (84%) with some degree of altered consciousness and 25 patients (100%) with nuchal rigidity. In all instances, the cerebrospinal fluid exhibited pleocytosis with a predominance of polymorphonuclear leukocytes. Eleven patients (44%) were afebrile on presentation. Of 22 surviving patients, 10 (45%) were afebrile without subsequent fever after administration of the initial dose of antibiotics, in 5 (23%) fever resolved within 24 hours, and in 6 (27%) fever resolved within 48 hours of treatment; there was no instance of prolonged or secondary fever noted. Death occurred in 3 cases (12%). Bacterial meningitis is uncommon in older children. As compared with younger children, older children with bacterial meningitis commonly present without fever and tend to have their fever resolve shortly after effective antibiotic therapy is initiated without manifesting prolonged or secondary fever patterns. Haemophilus influenzae type b is a common cause of bacterial meningitis in children aged 6 years or older; empirical antibiotic therapy in this clinical situation should include treatment of this pathogen. PMID- 2321611 TI - Newborn screening for hemoglobinopathies in Colorado. The first 10 years. AB - In Colorado, newborn screening for hemoglobinopathies by cellulose acetate and citrate agar electrophoresis of dried capillary blood spots was established in 1979. We reviewed the results of screening 528,711 infants through 1988. Forty seven infants with sickle cell diseases and 27 infants with other hemoglobin diseases were identified. The initial screening failed to detect sickle cell anemia in 4 infants, but the hemoglobinopathy in 3 of these infants was diagnosed correctly by routine retesting of those with suspected sickle cell trait. A total of 47 infants with sickle cell diseases were followed through September 1989. There was no mortality among these infants. The screening test identified 3779 infants (1:140 births) with a suspected hemoglobin trait; confirmatory retesting was obtained in 53%. The results of our experience confirm the value of newborn screening for hemoglobinopathies but suggest that a more sensitive test would improve the program. PMID- 2321612 TI - The effect of postpartum lactation counseling on the duration of breast-feeding in low-income women. AB - We investigated the effectiveness of a program of intensive postpartum support for low-income, breast-feeding women and identified potential predictors of prolonged breast-feeding in this population. Ninety-seven low-income women were randomized to receive intensive postpartum education and support for breast feeding or to receive only the routine assistance provided by the obstetrical nurses. Both groups were telephoned 6 weeks post partum to determine the method of infant feeding then, and those still breast-feeding were contacted monthly until complete weaning had occurred. No significant difference in breast-feeding duration between the two groups was noted. There was no association between duration of nursing and race, marital status, or the need to return to work or school. Earlier age at introduction of supplement, younger maternal age, and participation in prenatal classes predicted breast-feeding duration by logistic regression. PMID- 2321613 TI - Body image and eating behavior in adolescent boys. AB - A questionnaire about attitudes toward body weight and shape, and eating and weight control practices, was administered to 895 adolescent boys. Overall, 42% were dissatisfied with their weight and 33% with their body shape. Sixty-eight percent of the dissatisfied normal weight boys thought they were underweight and 32% thought they were overweight. Subjects dissatisfied with their body shape were most likely to desire an increased chest and arm size and decreased abdomen size. Binge eating (24%) and fasting (12%) were the most prevalent eating practices and were more common in boys dissatisfied with weight or shape. There was no difference in prevalence of eating practices between boys wishing to gain and boys wishing to lose weight. Although many boys were concerned about body weight and shape, they wished to increase weight and muscularity, rather than lose weight. Binge eating was common, but was not related to the binge-purge cycle described in girls, because losing weight is not a major concern, and other weight control practices were not more common among boys who wanted to lose weight vs gain. PMID- 2321614 TI - Pregnancies in human immunodeficiency virus-infected sex partners of hemophilic men. The Hemophilia-AIDS Collaborative Study Group. AB - We investigated 24 completed pregnancies of 20 healthy, human immunodeficiency virus (HIV)-seropositive sex partners of 20 seropositive hemophilic men. One woman had recurrent herpes simplex type 2 infection; no woman was known to use illicit drugs or to have other purported cofactors for vertical HIV transmission. For 8 offspring, the mothers learned of their partners' serostatus and received counseling against pregnancy prior to the fifth month of gestation; for 9 offspring (37.5%), the mothers learned of their own seropositivity and received counseling prior to the fifth month. Acquired immunodeficiency syndrome developed in 7 (35%) of 20 fathers, 4 of whom died; HIV-related symptoms developed in 4; severe liver disease developed in 2; and 7 (35%) were in good health. In four mothers (20%) HIV-related symptoms developed. Five offspring were breast-fed for 2 days to more than 3 years, two while the mother was known to be seropositive; four of these were seronegative and healthy, and one was seropositive at 30 months of age and had persistent cervical lymphadenopathy at 48 months of age. Infants were born at term; median birth weight was 2.86 kg. Solely on the basis of serologic studies and symptoms for those with more than 15 months of follow up, the minimum perinatal transmission rate for this group of women without putative transmission cofactors (drug usage, promiscuity, malnutrition, HIV symptoms) was at least 25%, a rate comparable to that reported for women in other risk groups. PMID- 2321615 TI - P values. PMID- 2321616 TI - Career counseling practices in pediatric residency training programs. AB - Although there has been an emphasis on career satisfaction in pediatrics and on motivators that impact on resident career selection, little attention has been directed toward the career development process in pediatric residency training. This report summarizes the results of a survey conducted of 155 pediatric residency program directors about their counseling practices. Implications of the results and recommendations are discussed to improve this process. PMID- 2321617 TI - Radiological case of the month. Obstructing annular pancreas. PMID- 2321618 TI - Picture of the month. Trisomy 8/mosaic syndrome. PMID- 2321619 TI - Use of electric blankets and risk of testicular cancer. AB - Electric blankets are an important domestic source of electromagnetic fields (EMF) because of the relatively high intensity of emission, prolonged exposure, and intimate contact with the source. In a case-control study of testicular cancer in western Washington during 1981 to 1984, the relation between EMF exposure from electric blankets and the occurrence of testicular cancer was examined. The respective proportions of cases and controls who reported the use of an electric blanket were almost identical (age-adjusted rate ratio (RR) = 1.0, 95% confidence interval (CI) 0.7-1.4). Distributions of the duration of use were also very similar in cases and controls. Compared with controls, the frequency of use of an electric blanket was slightly lower in men with seminoma (RR = 0.7, 95% CI 0.5-1.2) and slightly higher among men with nonseminoma germ cell tumors (RR = 1.4, 95% CI 0.9-2.3). Overall, the results of this study suggest that increased exposure to EMF from electric blankets contributes little, if at all, to the risk of testicular cancer in adult white men. PMID- 2321620 TI - Magnetic field exposure from electric appliances and childhood cancer. AB - The effect on childhood cancer of prolonged exposure to 60-H magnetic fields from electric appliances was examined using interview data from a recently completed case-control study. Exposures of children aged 0-14 years whose incident cancers were diagnosed between 1976 and 1983 and who resided in the Denver, Colorado, Standard Metropolitan Statistical Area were compared with those of controls selected by random digit dialing, matched on age, sex, and telephone exchange area. Parents of 252 cases and 222 controls were interviewed at home about the use of electric appliances by the mother during pregnancy (prenatal exposure) and by the child (postnatal exposure). After adjustment for income, prenatal electric blanket exposure was associated with a small increase in the incidence of childhood cancers (odds ratio (OR) = 1.3, 95% confidence interval (CI) 0.7-2.2) that was more pronounced for leukemia (OR = 1.7, 95% CI 0.8-3.6) and brain cancer (OR = 2.5, 95% CI 1.1-5.5). Postnatal exposure to electric blankets was also weakly associated with childhood cancer (OR = 1.5, 95% CI 0.6-3.4), with a larger but imprecise association with acute lymphocytic leukemia (OR = 1.9, 95% CI 0.6 6.5). Water beds and bedside electric clocks were unrelated to childhood cancer incidence. Results are limited by nonresponse and imprecision resulting from the rarity of appliance use, especially for subgroups of cases. Nonetheless, electric blankets, one of the principal sources of prolonged magnetic field exposure, were weakly associated with childhood cancer and warrant a more thorough evaluation. PMID- 2321621 TI - Epidemiology and exposure to electromagnetic fields. PMID- 2321622 TI - Neuroblastoma and parental occupation. AB - A matched case-control study of neuroblastoma investigated parental occupational risk factors. Cases diagnosed in 1970-1979 were identified through tumor registries in the Greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone exchange. Parents of 104 matched pairs were interviewed by telephone. In contrast to results of a previous study, no significant associations were noted for paternal employment in a job cluster of occupations in electricity, electronics, insulation, utility, and printing; in jobs with electromagnetic field exposure; or in jobs as workers in electronics. Six cases and one control, however, had a father or mother who worked in electrical or electronic products assembly. PMID- 2321623 TI - Atypical metaplasia and incidence of bronchogenic carcinoma. AB - The prognostic implication of atypical squamous metaplasia of the respiratory tract has been uncertain, especially for mild atypia. The relation between degree of severity of atypical metaplasia as detected by sputum cytology and incidence of bronchogenic carcinoma was assessed among 14,414 men aged 45 years or older who smoked one or more packs of cigarettes per day. Trial participants underwent sputum cytologic evaluations every 4 months for an average of 7.4 years as part of the Cooperative Early Lung Cancer Detection Program of the National Cancer Institute and were followed for the development of lung cancer between 1971 and 1983 at three institutions: The Johns Hopkins University, the Memorial Sloan Kettering Cancer Center, and the Mayo Clinic. Analysis with logistic regression controlling for age, race, occupational exposures to lung carcinogens, average number of cytology records per year, and smoking habits revealed that the estimate of the relative rate (RR) of developing bronchogenic carcinoma was greater among men who had mild atypia as compared with men who had negative cytology readings, but there were marked differences among institutions (RR = 1.1, 95% confidence interval (Cl) 0.8-1.5 at The Johns Hopkins University; RR = 1.6, 95% Cl 1.1-2.5 at the Memorial Sloan-Kettering Cancer Center; and RR = 2.5, 95% Cl 1.6-4.0 at the Mayo Clinic). Results suggest that mild atypia as detected by cytologic evaluation of sputum is an indicator of a modest elevation in risk of bronchogenic carcinoma. PMID- 2321624 TI - Social class and the black/white crossover in the age-specific incidence of breast cancer: a study linking census-derived data to population-based registry records. AB - An unexplained racial crossover in breast cancer rates in the United States has been apparent since 1969: among women over age 40 years, the rate is higher among white compared with black women, while among women under age 40, the reverse is true. To explore the contribution of social class to this phenomenon, the present study used 1980 census block-group data to generate population-based age-specific breast cancer rates stratified by race and class. Cancer data included all black women (n = 405) and white women (n = 4,259) diagnosed with primary breast cancer during 1979-1981 in the San Francisco Bay Area Resource for Cancer Control registry. Among women under age 40, the black/white incidence ratio among women from predominantly working class block-groups was 1.08 (95% confidence interval (CI) 0.74-1.56), but among those from non-working class block-groups, the black/white ratio equaled 1.96 (95% CI 1.17-3.26). Among women age 40 years or over, the black/white incidence ratio among women from working class block-groups was 0.78 (95% CI 0.68-0.89), but was 0.98 (95% CI 0.78-1.23) among women from non working class block-groups. These findings underscore the class-based nature of the observed crossover and pose a challenge to accepted theories of breast cancer etiology. Possible risk factors contributing to these findings are discussed, including induced abortion and oral contraceptive use prior to first full-term pregnancy. PMID- 2321625 TI - Agreement between interview information and physician records on history of menopausal estrogen use. AB - A case-control study of the association between replacement estrogen use and breast cancer risk was conducted between 1975 and 1980 on Oahu, Hawaii. Data from this study were used to compare menopausal estrogen histories obtained through a personal interview with information from the subject's physician(s) or clinical records. The sample included 344 breast cancer cases, 344 hospital controls, and 344 neighborhood controls. Study participants included Japanese and white women aged 45-74 years who were residents of Oahu. Interviewers asked participants whether they had ever used replacement or menopausal estrogens for 1 month or longer. The month and year of initial use and the duration of use for each preparation were recorded for the users. Questions were also asked about a number of other medications. Information on estrogen use from the users and nonusers was then verified by the physician(s) or clinic(s) named by the study subject. The results showed moderate to substantial agreement between users and physicians on ever/never use of estrogens (kappa = 0.74), duration of estrogen use (intraclass correlation coefficient (rI) = 0.54), and age at initial use of estrogens (rI = 0.57). There was no differential misclassification by the case-control status of the subject. Agreement tended to be better for Japanese subjects, younger subjects, nonsmokers, and those of higher socioeconomic status, as measured by two indicators, college education and home ownership. Agreement was also negatively influenced by the duration of estrogen use and length of recall. These results suggest that women can recall estrogen use with a high degree of accuracy and support the use of a personal interview for obtaining information on replacement estrogens in case-control studies. PMID- 2321626 TI - Low incidence of hospitalization with gallbladder disease among blacks in the United States. AB - Low rates of gallbladder disease among blacks have been reported but not systematically studied. The authors investigated the rate of hospitalization with a diagnosis of gallbladder disease in the follow-up in 1982-1984 of the first National Health and Nutrition Examination Survey, a population-based study conducted across the United States in 1971-1975. Based on hospital discharge diagnoses of gallbladder disease, 368 cases were identified for the period 1971 1984 among 10,551 persons, aged 25-74 years, who denied gallbladder disease at the baseline examination. The crude incidence of gallbladder disease per 1,000 person-years was 2.59 for white men, 1.45 for black men, 4.09 for white women, and 2.35 for black women. Controlling for obesity, parity, ethanol consumption, use of diuretics, use of oral contraceptives, and two indicators of socioeconomic status, the authors found that the hazard rate of hospitalization with gallbladder disease increased with age for white women and decreased for black women. The hazard ratio for black women compared with white women at 30 years of age was 0.71 with a 95% confidence interval of 0.52-0.96, but at age 70, it was 0.18 with a 95% confidence interval of 0.09-0.37. For women, obesity and parity were important risk factors for gallbladder disease (p less than or equal to 0.001), and the use of diuretics was marginally associated (p = 0.08). Black men compared with white men had a hazard rate of gallbladder disease of 0.53 with a 95% confidence interval of 0.24-1.16. For men, increasing age was related to gallbladder disease (p less than 0.001), and obesity was weakly related (p = 0.06). The black/white hazard ratios decreased further when controlling for socioeconomic status, persisted if the study population was limited to those hospitalized during follow-up, and increased slightly for cases with an acute complication of gallbladder disease. Thus, differential access to medical care may not explain the lower rate among blacks. PMID- 2321627 TI - Influence of race, tobacco use, and caffeine use on the relation between blood pressure and blood lead concentration. AB - A number of studies have suggested a small to moderate positive relation between blood pressure and blood lead concentration in males (2-4 mmHg/In(microgram/dl]. However, this 1986 study of San Francisco bus drivers suggests larger relations in black males (n = 132) for both systolic pressure (7.5 mmHg/In(microgram/dl] and diastolic pressure (4.7 mmHg/In(microgram/dl] at very low blood lead concentrations (2-21 micrograms/dl). This increase appears to result from negative confounding, particularly after taking into account tobacco use. Relations are even larger in blacks who infrequently use caffeine (16.7 and 10.4 mmHg/In(microgram/dl) for systolic and diastolic pressure, respectively). In contrast, a negative relation between systolic pressure and blood lead concentration (-5.7 mmHg/In(microgram/dl] is suggested in nonblack males (n = 117). These findings indicate that race, lead accumulation, and physiologic effects related to caffeine use (e.g., catecholamine effects) may interact to produce marked differences in effect on blood pressure. PMID- 2321628 TI - Total and HDL cholesterol and their correlates in elderly men in Finland, Italy, and The Netherlands. AB - In 1984 and 1985, 25-year follow-up studies were carried out in the Italian, Finnish, and Dutch cohorts of men originally examined around 1960 in the Seven Countries Study. Risk factors for coronary heart disease were determined in 2,255 men aged 65-84 years. The average serum total cholesterol levels of the elderly men in Finland and the Netherlands were similar, at around 236 mg/dl (6.10 mmol/liter). The average serum total cholesterol levels of the elderly men in Italy were about 10 mg/dl (0.26 mmol/liter) lower. During 25 years of follow-up, the average serum total cholesterol level increased by 29 mg/dl (0.75 mmol/liter) among the Italian survivors, decreased by 23 mg/dl (0.59 mmol/liter) in the Finnish survivors, and did not change in the Dutch survivors. Age, Quetelet index, and coffee consumption were the most important correlates of total cholesterol in these elderly men. Quetelet index, alcohol consumption, age, and cigarette smoking were significantly associated with high density lipoprotein (HDL) cholesterol. The results of this study suggest that modifiable risk factors are related to total and HDL cholesterol in elderly men in different cultures. PMID- 2321629 TI - Food predictors of plasma beta-carotene and alpha-tocopherol: validation of a food frequency questionnaire. AB - Nutrient intakes from a food frequency questionnaire are usually calculated as the product of frequency of intake and nutrient composition of the food, summed over the food items. This involves assumptions about the accuracy of recording, food composition data, stability during storage and preparation, and bioavailability. This usual method of calculation was compared with one using empirical weights derived by multivariate linear regression. Food intakes reported on a food frequency questionnaire by Boston, Massachusetts, area subjects in 1982-1985 were used to predict plasma levels of beta-carotene among 370 male and female nonsmokers and plasma levels of alpha-tocopherol among 339 male and female nonusers of vitamin supplements. Nutrient intake computed using empirical weights yielded a significant correlation with plasma beta-carotene (r = 0.43, p = 0.0001), similar to the correlation using nutrient intake calculated from food composition tables (r = 0.38, p = 0.0001). However, the use of empirical weights significantly improved the correlation of vitamin E intake with plasma alpha-tocopherol levels (r = 0.32, p = 0.0001), compared with the weak correlation obtained using the food composition table method to calculate intake (r = 0.16). The results support the validity of published food composition data used to compute carotenoid intake and illustrate the potential utility of empirically derived weights for foods to predict plasma levels of some nutrients. PMID- 2321630 TI - Lyme disease in outdoor workers: risk factors, preventive measures, and tick removal methods. AB - A statewide cross-sectional study of risk factors for seropositivity for antibody to Borrelia burgdorferi in outdoor workers in New Jersey was performed in September and October 1988. The crude odds ratio associated with exposure to ticks on the primary state job was 2.2 (95% confidence interval (CI) 0.7-9.0). After adjustment for multiple confounding variables with logistic regression, the adjusted occupational tick exposure odds ratio was 5.1 (95% CI 1.1-23.6). Additional analyses revealed that any use of insect repellent or antibiotics may have decreased the risk of Lyme disease in these workers (adjusted odds ratios for not using insect repellent or antibiotics were 2.0 (95% CI 1.0-4.0) and 2.3 (95% CI 0.8-6.7), respectively). These data suggest that Lyme disease is a hazard of outdoor work and that increased recognition of this fact will be necessary to prevent Lyme disease in these workers. PMID- 2321631 TI - Risk factors for wound infections after total knee arthroplasty. AB - Wound infections are an infrequent but serious complication of total knee arthroplasty. Between January 1984 and November 1987, 20 of 243 (8.2%) patients at two affiliated hospitals developed surgical wound infections following 259 total knee arthroplasty procedures performed in clean-air operating rooms. Eighteen (90%) of the patients had deep infections; nine required removal of the prosthesis. A single surgeon (surgeon X) was associated with 18 of the procedures that had subsequent infection (risk ratio (RR) = 9.4, 95% confidence interval (CI) 2.2-39), and an investigation was carried out in an effort to explain the difference in infection rates between surgeon X and other surgeons. In a cohort study, stratified analyses identified a preoperative American Society of Anesthesiologists (ASA) physical status class greater than or equal to 3, surgeon X, and early postoperative use of a continuous passive motion device as risk factors associated with surgical wound infection following total knee arthroplasty procedures. Logistic regression analyses identified being a patient operated on by surgeon X with an ASA class greater than or equal to 3 as the only significant independent risk factor for total knee arthroplasty-associated surgical wound infections (RR = 9.3, 95% CI 2.8-31). The effect due to surgeon X could not be explained by receipt or timeliness of administration of antimicrobial prophylaxis, type of prosthesis inserted, duration of operation, postoperative use of continuous passive motion, or underlying etiology of joint disease. The authors conclude that surgical technique and patient's severity of illness were the primary determinants of surgical wound infection after total knee arthroplasty. This study demonstrates the complexity of epidemiologic investigation of surgical wound infections and the importance of considering patient severity of illness when interpreting surgeon-specific infection rates. PMID- 2321632 TI - Methods for analyzing combined data from studies of workers exposed to low doses of radiation. AB - Epidemiologic studies of workers exposed occupationally to protracted low doses of radiation provide a direct assessment of health effects resulting from such exposure and thus supplement information provided by studies of populations exposed at high doses of radiation and high dose rates. Analyses based on combined data from several studies can be expected to provide a more thorough assessment of low dose occupational studies and more precise risk estimates than can be obtained from any single study. Statistical methods for conducting such combined analyses are discussed, and different approaches, such as basing analyses on various levels of aggregation of exposure data, are compared and evaluated. Emphasis is given to methods for obtaining risk estimates and confidence limits that can be appropriately compared with estimates that form the basis for current radiation protection standards; these estimates have been obtained through extrapolation from high dose data. Methods are illustrated using combined data on workers at three US Department of Energy facilities: the Hanford Site, Richland, Washington; the Oak Ridge National Laboratory, Oak Ridge, Tennessee; and the Rocky Flats Nuclear Weapons Plant, Denver, Colorado. PMID- 2321633 TI - Assigning race to occupational cohorts using census block statistics. AB - Race is an important determinant of disease frequency, yet the race of subjects in retrospective epidemiologic studies is frequently unknown. If addresses are available, the race of study subjects may be estimated from the racial composition of the blocks on which they have resided. Such information can be obtained from census block statistics for Standard Metropolitan Statistical Areas and, with the 1990 Census, probably for the entire United States. The authors assigned black race to persons on blocks with greater than 60% black residents and white race to those residing on blocks containing less than 40% blacks. The validity of the procedure was tested on 341 decedents of known race who resided at the time of death within the Detroit, Michigan, Standard Metropolitan Statistical Area. Thirteen individuals who lived on blocks with 40-60% blacks were excluded from analysis, as well as 18 others for whom racial composition of blocks could not be ascertained. In 293 (94%) of the remaining 310 persons, race assigned on the basis of census information agreed with race obtained from death certificates. This method should prove useful for assigning race to study subjects lacking racial identification. PMID- 2321634 TI - Re: "Reporting Accuracy among Mothers of Malformed and Nonmalformed Infants". PMID- 2321635 TI - Re: "A Study of Repeatability of Dietary Data over a Seven-Year Period". PMID- 2321636 TI - Re: "Plasma Triglyceride as a Risk Factor for Coronary Heart Disease: the Epidemiologic Evidence and Beyond". PMID- 2321637 TI - Re: "Use of Modeling in Infectious Disease Epidemiology". PMID- 2321638 TI - Re: "Comparing Proportion Exposed in Case-Control Studies Using Several Control Groups". PMID- 2321639 TI - 19th annual scientific meeting abstracts. National Kidney Foundation. PMID- 2321640 TI - A proposal to improve the attractiveness of nephrology as a subspecialty choice for residents in internal medicine. PMID- 2321641 TI - Malpositioned peritoneal dialysis catheters: a critical reappraisal of correction by stiff-wire manipulation. AB - Tenckhoff peritoneal dialysis (PD) catheter malposition is one of the leading causes of catheter malfunction. Fluoroscopically directed stiff-wire manipulation of malpositioned PD catheters has been advocated as a method of catheter salvage. Two hundred eighty-nine single-cuff PD catheters were placed surgically into 203 patients during this 4-year study. Thirty-three patients developed catheter malfunction attributed to malposition. Forty-eight stiff-wire manipulations were performed on these patients. Thirty-eight (78%) of the manipulations were described as successful at the time of transfer from radiology. However, only 25 (51%) and 12 (25%) resulted in functioning catheters at 1 week and 1 month, respectively. Only 11 of 33 patients who underwent manipulation had functional prolongation of catheter life beyond 1 month. The PD catheter was replaced by a column-disk PD catheter without additional catheter dysfunction in six patients. A second single-cuff Tenckhoff PD catheter was inserted in another six patients. Three of these six catheters again malpositioned. We conclude that stiff-wire manipulation is a useful and safe technique worth using on a limited basis for the initial episode of catheter malposition. Catheters that repetitively malposition should be replaced with a catheter that is resistant to malpositioning. PMID- 2321642 TI - The transtubular potassium concentration in patients with hypokalemia and hyperkalemia. AB - It is advantageous to make an independent assessment of the potassium (K) secretory process and the luminal flow rate in the renal cortex to evaluate K handling by the kidney during hypokalemia or hyperkalemia. The transtubular potassium concentration gradient (TTKG) is a semiquantitative index of the activity of the K secretory process. The purpose of this study was to define expected values for the TTKG in normal subjects with hypokalemia or following an acute K load. During hypokalemia of non-renal origin, the TTKG was 0.9 +/- 0.2; in contrast, the TTKG was significantly higher during the hypokalemia of hyperaldosteronism, 6.7 +/- 1.3. The TTKG was 11.8 +/- 3.6, 2 hours after normokalemic subjects received 0.2 mg 9 alpha-fludrocortisone (9 alpha-F). To obtain expected values during hyperkalemia, normal subjects ingested 50 mmol potassium chloride; 2 hours later, the TTKG was 13.1 +/- 3.8. Therefore, the expected value for the TTKG must be interpreted relative to the concentration of K in the plasma. Circumstances were also defined where the TTKG is low despite hyperaldosteronism, namely, during a water diuresis and pre-existing hypokalemia. PMID- 2321643 TI - Indomethacin does not impair cellular potassium uptake in the rat. AB - Based primarily on a single case study, it has been suggested that nonsteroidal antiinflammatory drugs (NSAIDs) may impair cellular potassium uptake, and that this effect may contribute to NSAID-induced hyperkalemia. To explore this possibility, we studied rats that had been pretreated with indomethacin or normal saline and subsequently bilaterally nephrectomized and potassium loaded. There were no significant differences between the indomethacin and control groups in the baseline, final, or increment in plasma potassium concentration after a potassium load. Similar results were obtained whether potassium was given intraperitoneally (IP) or intravenously (IV). Serum indomethacin levels confirmed that indomethacin was well absorbed transperitoneally. We conclude that in nephrectomized but otherwise healthy rats, high-dose indomethacin does not impair the cellular uptake of an acute potassium load. PMID- 2321644 TI - High fluoride exposure in hemodialysis patients. AB - The observation of higher plasma flouride levels in our hemodialysis (HD) patients than our continuous ambulatory peritoneal dialysis (CAPD) patients (4.0 +/- 0.5 mumol/L [n = 17] v 2.5 +/- 0.3 mumol/L [n = 17], P less than 0.005) prompted an evaluation of fluoride metabolism during HD. We found that serum fluoride was completely ultrafiltrable across cuprophane membranes (99% +/- 4%) and that HD produced acute changes in plasma fluoride levels that correlated well with the fluoride gradient between plasma and dialysis fluid at the start of dialysis. Our HD fluids contained significantly higher fluoride concentrations than were present in commercially prepared peritoneal dialysis fluid. Our fluids are prepared from fluoridated tap water that is purified by reverse osmosis (RO). We conclude that the different concentrations of fluoride in our dialysis fluids account for the differences in the plasma flouride concentrations between our dialysis groups. Since many HD units rely on RO systems to purify fluoridated tap water, it is likely that many HD patients are being exposed inadvertently to increased concentrations of fluoride. PMID- 2321645 TI - Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients. AB - The objective of this study was to quantitate the improvement in exercise capacity produced in anemic chronic hemodialysis (HD) patients after correction of their anemia with recombinant human erythropoietin (rHuEPO). The maximal exercise capacity and quadriceps strength of 19 anemic HD patients was tested before and after correction of the anemia with rHuEPO. A progressive work exercise protocol (PWET) on a cycle ergometer was used to compare measurements of maximal oxygen uptake (VO2max), maximal heart rate, and subjective assessment of fatigue during the test. Measurements of quadriceps strength were performed before the cycle ergometer studies. At baseline, all patients had reduced VO2max (15.3 +/- 5.4 mL/kg/min) and maximal exercise heart rates (138.5 +/- 23.9 beats/min). rHuEPO increased the mean hematocrit from 21.2% to 35%, and this was associated with a 17% increase (P less than 0.0005) in the VO2max. At any specified work load, rHuEPO treatment decreased heart rate, minute ventilation, and the subjective perception of fatigue. Both isometric and isokinetic measurements of quadriceps strength were improved following administration of rHuEPO. The maximal exercise heart rate was decreased in comparison to the baseline measurements (P less than 0.04), suggesting that in contrast to normal subjects, HD patients stop exercise before oxygen transport limitations are reached. In this unselected group of chronic HD patients, rHuEPO produced clinically significant improvements in both aerobic exercise capacity and isometric and isokinetic quadriceps strength. The improvement in aerobic capacity was substantially less than would have been expected from the correction of a comparable degree of anemia in non-HD patients. None of the 19 treated patients attained the exercise performance level predicted for a sedentary normal subject. PMID- 2321646 TI - Chronic mesangiolytic glomerulopathy in a patient with SC hemoglobinopathy. AB - Numerous cases of glomerular disease in sickle cell patients have been reported. Glomerular disease in SC double heterozygotes has not been reported despite its equal prevalence in adults. We herein report a case of mesangiolytic glomerulopathy in a patient with SC disease. PMID- 2321647 TI - Onset of dialysis encephalopathy in cyclosporine-treated renal allograft recipients. AB - Three patients who developed typical features of dialysis encephalopathy following renal transplantation are presented. No patient had evidence of overt neurological dysfunction pretransplantation. All patients were taking cyclosporine at the time of onset of neurological disease. Two patients died as a result of their neurological condition. The third patient made a satisfactory recovery. Factors responsible for the onset of dialysis encephalopathy in the renal posttransplantation period are discussed. We propose that cyclosporine may have been an important precipitating factor of the neurological syndrome of these patients. PMID- 2321648 TI - Adipsic hypernatremia complicated by hyponatremia. PMID- 2321649 TI - Reduced doxorubicin waste through use of multiple-dose vials. PMID- 2321650 TI - Benefits of an integrated hospital information system. PMID- 2321651 TI - Pharmacokinetics-monitoring form. PMID- 2321652 TI - An unsavory concoction. PMID- 2321653 TI - External quality assurance committee for drug information services. AB - Use of an external quality assurance committee to assess the performance of a drug information service is described. At the St. John's University Drug Information Center, responses to requests for drug information are provided via telephone, with written consultations or bibliographies provided on request. All telephone queries and responses are tape-recorded so that the oral responses to requests can be evaluated. In September 1986, the center initiated a quality assurance program that involved a 10-member external review committee composed of local pharmacists representing eight practice areas. A standardized evaluation form containing performance criteria was used. Performance with respect to each criterion, excluding timeliness and consistency of the response, was rated according to a four-point scale. Mean scores for all drug information skills were determined on the basis of the difficulty rating of the request. A total of 25 consultations were evaluated during a six-month pilot period. The most accurately answered requests were those pertaining to adverse drug reactions, teratogenicity, injectable drug compatibility, and drug-drug interactions. The least accurately answered questions pertained to product identification. Mean scores for the low-difficulty and intermediate-difficulty questions were much lower than those for the high-difficulty questions for all performance areas except oral communication. Use of an external quality assurance committee proved to be an objective, valid way of ensuring the accuracy and completeness of drug information consultations. PMID- 2321654 TI - Revising a drug information center quality assurance program to conform to Joint Commission standards. AB - Revisions in the quality assurance (QA) program for a drug information center (DIC) at a large community teaching hospital are described. The initial QA program, implemented in 1984, was based on 25 specific criteria and on the periodic evaluation process that was stressed by the Joint Commission on Accreditation of Hospitals at that time. In 1985 the hospital was surveyed for reaccreditation, and the Joint Commission stressed a new approach to QA that replaced periodic evaluation with an ongoing, planned process. Accordingly, the 25 specific QA criteria were replaced with 10 general indicators. Since 1985 the Joint Commission has shifted its focus to patient outcomes. The 10 general criteria have now been reduced to two specific criteria: the total number of questions received by the DIC staff and the percentage of responses that are appropriate. Drug information responses given by the DIC pharmacist as well as by the frontline pharmacists are monitored. As Joint Commission requirements for QA programs evolve, the QA program for this DIC is revised to ensure that it always meets the current standards. PMID- 2321655 TI - Problems encountered in using written criteria to assess drug information responses. AB - Problems encountered in using written criteria to evaluate drug information responses during a study designed to determine whether simple requests were being unnecessarily submitted to a drug information center are described. Drug information questions that had been answered by a drug information center from June 1985 to June 1986 using defined references were chosen for evaluation. The center's responses to the 156 questions were paired with those of senior pharmacy students, who used the same references. Two experienced drug information pharmacists used a 6-point scale to evaluate the correctness, appropriateness, and completeness of each response, as well as the amount of extraneous material it contained. Interrater agreement was acceptable with respect to appropriateness, completeness, and amount of extraneous material; it was unacceptable with respect to correctness. When the judges re-evaluated the responses by using more explicit criteria for correctness, interrater agreement improved. The analysis excluded 32 responses that the judges found difficult to evaluate. Difficulties in assessing drug information responses arose from a lack of objective evaluation criteria, the wording of the request, the scope of the reference sources used, a lack of consistency between equivalent references, evaluator bias, and incomplete documentation. Efforts to determine whether simple drug information requests were being unnecessarily submitted to the drug information center were confounded by difficulty in using written criteria to judge the quality of responses. PMID- 2321656 TI - Assessing the quality of pharmacist answers to telephone drug information questions. AB - A quality assurance (QA) program is described in which frontline pharmacists were asked test drug information questions via anonymous telephone calls. The program was instituted at a university hospital that began providing decentralized pharmaceutical services in 1985. Questions were developed on the basis of a pilot study conducted to determine the types and complexity of drug information questions received by frontline pharmacists at the hospital. Data on departmental clinical productivity were used to determine the number of questions that would be posed during each shift in the various service areas. The questions were posed during a 10-day period; the pharmacists were aware of the program, but the callers did not identify their affiliation with it. In response to 105 questions asked, 86 were judged to have been answered correctly, 13 answers were deemed incomplete, and 6 were judged incorrect. Pharmacists were more likely to respond incorrectly to complex questions and questions posed during the night shift. As a result of the audit, staff members with advanced clinical knowledge were asked to help less experienced pharmacists, the position of assistant director for drug information and staff development was created, and educational programs were instituted. The QA audit has been repeated twice. Posing test drug information questions via anonymous telephone calls is effective in assessing the quality of drug information provided by pharmacists in patient-care areas. PMID- 2321657 TI - Microcost analysis of inpatient dispensing and administration of oral solids. AB - The labor cost of dispensing, administering, and monitoring unit dose oral solid dosage forms (UDs) in a large teaching hospital was determined by microcost analysis. The costs associated with UDs dispensed by the midnight central pharmacy and by a satellite pharmacy were evaluated by use of both work-sampling and time-and-motion studies. Pharmacy personnel activities were classified as direct, auxiliary, or nonproductive. A nursing productivity index was used to determine the nursing time consumed in the administration and monitoring of UDs. The pharmacy labor cost was lowest ($0.14 each) for UDs dispensed from the central pharmacy in the 24-hour medication cart. For each UD that was not dispensed in the 24-hour cart, the labor cost was $0.25 for the central pharmacy and $1.37 for the satellite pharmacy. It took nurses 223.8 sec to administer and monitor a scheduled UD, for a cost of $0.82. The total nursing time spent per nonscheduled UD for administration and monitoring was 574.2 sec; the cost was $2.11. Microcost analysis can be used to isolate the costs of dispensing oral solids in an inpatient setting. PMID- 2321658 TI - Drug use in a trauma intensive-care unit. AB - Medication prescribing patterns and costs of specific drug therapies in a trauma intensive-care unit (TICU) were studied. Demographic data and total drug use (scheduled, p.r.n., and single-dose medications) were recorded for all patients admitted to a TICU whose length of stay exceeded 24 hours. Scheduled and p.r.n. medications were categorized into major drug classes for purposes of analysis. Cost estimates were calculated for all scheduled medications. Correlations were made between demographic variables, injury severity indices, drug use, and length of stay by using simple linear regression. A one-way ANOVA was used to compare drug use between the trauma types. For the 278 patients who met the inclusion criteria, the mean +/- S.D. number of drugs prescribed was 9.1 +/- 6.5. Scheduled medications accounted for 58% of total drug use. Mean +/- S.D. duration of scheduled drug therapy was 5.0 +/- 4.8 days. Age (by decade), injury severity score, trauma score, and length of stay correlated with total and scheduled drug use per patient. Drug use (total, scheduled, and p.r.n.) did not differ significantly by trauma type. Antimicrobial therapy, stress ulcer prophylaxis, and bronchodilator therapy accounted for more than 66% of all scheduled drugs used; total cost estimates for these three drug categories exceeded $47,000 over the six-month study period. Analgesics, antipyretics, sedatives, and muscle relaxants constituted nearly 75% of all p.r.n. drug orders. Drug use in the TICU was extensive. The drug categories identified in this study may be useful in future cost containment efforts and initiation of drug use evaluations. PMID- 2321659 TI - Pharmacist's response when the motives for a change in physician prescribing seem questionable. PMID- 2321660 TI - Identifying patients served simultaneously by more than one Veterans Affairs medical center. PMID- 2321661 TI - Refractometer screening of controlled substances in an operating room satellite pharmacy. PMID- 2321662 TI - Is a hospital negligent because one of its pharmacists allowed a medical resident to obtain an abortifacient for a girlfriend? PMID- 2321663 TI - Atherosclerosis, serum cholesterol and the homocysteine theory: a study of 194 consecutive autopsies. AB - A retrospective study examined 194 consecutive autopsies to determine the proportion of cases of atherosclerosis without elevated serum cholesterol, diabetes mellitus, or hypertension. The study cases were classified into four groups, according to the cause of death and the degree of atherosclerosis. Cases in Group 1, in which death resulted from complications of severe atherosclerosis, have a mean serum cholesterol of 186.7 +/- 41.8 mg/dL, and the cholesterol is less than 200 in 65% and less than 250 in 92% of cases. Cases in Group 2, with severe atherosclerosis dying of other diseases, have a mean serum cholesterol of 174.6 +/- 60.4 mg/dL, and the cholesterol is less than 200 in 79% of cases and less than 250 in 89% of cases. Cases in Groups 3 and 4, with moderate and minimal atherosclerosis, respectively, have mean serum cholesterol values of 172.3 +/- 54.8 and 143.5 +/- 47.8 mg/dL, and the cholesterol is less than 200 in 71% and 92% and less than 250 in 92% and 96% of cases, respectively. Serum cholesterol is significantly associated with severity of atherosclerosis in the total sample (P = 0.01). Three fourths of all cases (147/194) have neither diabetes nor hypertension, and in 74% of these cases (109/147) the cholesterol is less than 200 and in 92% (135/147) the cholesterol is less than 250. In 66% (80/122) of the cases with severe atherosclerosis, the disease developed without evidence of elevated serum cholesterol, diabetes, or hypertension. Blood homocysteine, which has been shown by other studies to be an independent risk factor for atherosclerosis, is recommended for assessing prognosis in these cases. PMID- 2321664 TI - Ibuprofen-associated renal impairment in a large general internal medicine practice. AB - The authors determined the incidence of ibuprofen-associated renal impairment and risk factors for its development in 1908 patients treated with ibuprofen using data from a computerized medical records system. Renal impairment occurred in 343 patients (18%). Multivariable analysis revealed six independent predictors of renal impairment: age, prior renal insufficiency, coronary artery disease, male gender, elevated systolic blood pressure, and diuretic use. They then tested the degree to which ibuprofen contributed to the development of renal impairment by evaluating a control group of 3933 acetaminophen recipients. Neither ibuprofen nor acetaminophen was among the independent predictors of risk when all patients were considered (adjusted odds ratio, 1.05; 95% Cl, 0.88-1.26). However, two subsets of at risk patients had an ibuprofen effect: patients greater than or equal to 65 years of age who received ibuprofen were at greater risk of renal impairment as compared to acetaminophen recipients (adjusted odds ratio, 1.34; 95% Cl, 1.05 to 1.72) as were patients with coronary artery disease (adjusted odds ratio, 2.54; 95% Cl, 1.38 to 4.68). Their results suggest that elderly patients and patients with coronary artery disease are at risk for ibuprofen associated renal impairment and therefore should have their renal function monitored when ibuprofen and possibly other nonsteroidal anti-inflammatory drugs are prescribed. PMID- 2321665 TI - Eicosanoid levels in CSF of premature infants with posthemorrhagic hydrocephalus. AB - The cerebrospinal fluid (CSF) of 11 premature infants suffering from posthemorrhagic hydrocephalus was examined by radioimmunoassay for prostaglandin (PG) E2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, thromboxane B2 (TxB2) and peptidoleukotrienes (LTC4/LTD4). The LTs were detected in the CSF of more of these patients (70%) than any of the other eicosanoids, and usually in the highest concentration. Among the 11 posthemorrhagic patients CSF eicosanoid levels were highest when determined soon after injury. Moreover, the variety of eicosanoids present, as well as concentrations, in these infants decreased with time. The types of eicosanoids most evident in the CSF of patients who required shunting were TxB2 and LTs, being present together in 5 of 6 (83%) of these infants. In contrast, 1 of 5 (20%) of the patients who did not require this neurosurgical intervention contained both TxB2 and LTs, the remaining having only one or neither eicosanoid. The highest average concentration for each eicosanoid studied was (pg/ml): PGE2, 628; PGF2 alpha, 985; PGD2, 1410; 6-keto PGF1 alpha, 544; TxB2, 486 and LTs, 1229. This study is the first to demonstrate that the CSF of preterm infants may contain a wide variety of eicosanoids and indicates that these lipids are a manifestation of neurological assault. PMID- 2321667 TI - Washington Metro jobfocus. Capitol attraction. PMID- 2321666 TI - Use of hepatic vein catheterization in the evaluation of patients with anasarca. AB - In patients with anasarca, the relative importance of cardiac, pulmonary and/or hepatic dysfunction is often difficult to determine. Conventional use of the Swan Ganz catheter helps to separate the contributions of right and left heart disease, but it is seldom used to evaluate liver dysfunction. This report describes passage of a Swan-Ganz catheter into the hepatic vein prior to pulmonary artery placement in 11 patients. Hepatic vein catheterization permitted wedged hepatic venography using contrast media and measurement of the wedged and free hepatic venous pressures. All 11 patients had pulmonary hypertension; three had cor pulmonale only, and the others had combinations of left and right heart failure. In addition, six patients had either a cirrhotic pattern on venography, or portal hypertension. Only three of these six patients had previous clinical evidence of liver disease. This study does not prove that identification of hepatic dysfunction by this method improves the outcome in such patients. However, this low risk modification of standard pulmonary artery catheterization provides additional information which is clinically useful in searching for and avoiding complications of cirrhosis, as well as offering a clearer understanding of pathophysiology in acute multisystem disease. PMID- 2321668 TI - Speaking of sex. PMID- 2321669 TI - How to feel good about being you. PMID- 2321670 TI - The lady and the parakeet. PMID- 2321671 TI - Foreign nurse screening: cause for alarm? PMID- 2321672 TI - Resuscitation status begins at home. PMID- 2321673 TI - Hepatitis D: yet another reason to get your HBV vaccine. PMID- 2321674 TI - Care is not punishment. PMID- 2321675 TI - Letting go of the ego. PMID- 2321676 TI - Nursing: a dysfunctional system? PMID- 2321677 TI - Cocaine. PMID- 2321678 TI - Crack. The nation's emergency. PMID- 2321679 TI - What's wrong with this stoma? PMID- 2321680 TI - A death in the family. PMID- 2321681 TI - How to give peritoneal chemotherapy. PMID- 2321682 TI - Syphilis. A new look at an old killer. AB - Thirty-four-year-old George Talbot was admitted to your medical/surgical unit with deep vein thrombosis of his left leg, probably related to intravenous drug abuse. So it's no surprise that Mr. Talbot is receiving heparin IV. Today, however, you notice that his physician has prescribed one dose (2.4 million units) of benzathine penicillin IM. You're not sure why until you check the patient's lab work. Mr. Talbot's rapid plasma reagin (RPR) test was reactive. The physician is treating Mr. Talbot for syphilis. PMID- 2321683 TI - Nursing at the front--of the cocaine wars. PMID- 2321685 TI - New York jobfocus. Bright lights, big town. PMID- 2321684 TI - Nurturance flows two ways. PMID- 2321686 TI - Recurrent hemangioma of the external auditory canal. AB - Hemangiomas of the external auditory canal rarely occur. These lesions have been reported to involve men in their sixth decade. This case report represents the fourth such lesion reported in the literature and the first to be seen in a woman. The clinical presentation, surgical therapy, and pathology are discussed. This tumor represents an unusual cause of hearing loss. PMID- 2321687 TI - Use of the bone conduction ABR Wave I response in determination of cochlear reserve. AB - Interest in bone-conducted stimulus auditory brainstem response (BC-ABR) testing has centered around evaluation of cochlear integrity in neonates and in patients who are difficult to evaluate audiometrically. The present study was designed to evaluate the Wave I component of the BC-ABR and to determine the utility of this response in assessment of cochlear reserve. The source of Wave I has been shown to be the distal eighth nerve. It was postulated that the presence or absence of this component would provide ear specific information useful for determination of cochlear integrity. In order to test this hypothesis, patients with a documented unilateral hearing loss were studied. Stimulus presentation was via the Radioear B-70 bone vibrator used in conventional audiometric assessment. Evoked potential responses were recorded at four presentation levels. Subjects had either normal hearing bilaterally or normal hearing in one ear and a mild-to-profound sensorineural hearing loss in the opposite ear. Our data indicate that the Wave I response, when measured in this fashion, is ear specific. Ear specificity was shown to be aided by good waveform morphology, as typically observed in younger subjects, and by a relatively large discrepancy in hearing thresholds between the normal and hearing-impaired ears. This technique may be of value in determination of cochlear reserve in patients with problematic masking dilemmas. PMID- 2321688 TI - Stapedectomy in residency--the UAB experience. AB - A retrospective study of the resident-performed stapedectomies at the University of Alabama-Birmingham over the last 10 years was done. "Satisfactory" results, depending on the audiologic criteria used, were obtained in 60-64 percent of cases, far below the 90-95% success rate of established otologic surgeons. The reason for the low success rate is extremely limited experience, an average of 0.78 cases per residency at this institution. Other training programs have reported slightly higher success rates, all in the 60-80 percent range, but each had a higher average number of stapedectomies per resident. Some comments and suggestions are offered on the continuing controversy of stapedectomy in residency. PMID- 2321689 TI - Evidence of central vestibulo-auditory dysfunction in atypical Cogan's syndrome: a case report. AB - Auditory and vestibular functions were investigated in a patient with atypical Cogan's Syndrome. The brainstem auditory evoked response revealed bilateral severe distortion of morphology and voltage diminution after potential I, greater in right ear recordings. Interwave latency I-III was increased bilaterally. Electronystagmographic studies showed nonfatigable direction changing positional nystagmus greater with right ear undermost and bilateral failure of optic suppression. Findings suggested bilateral pontocerebellar dysfunction. Correlation was found with the side of greater clinical manifestations. The patient had excellent recovery of auditory and vestibular functions with administration of corticosteroids within 2 weeks of the onset of hearing impairment. She was followed up with auditory and vestibular studies for 30 months. PMID- 2321690 TI - Meniere's symptoms resulting from bilateral otosclerotic occlusion of the endolymphatic duct: an analysis of a causal relationship between otosclerosis and Meniere's disease. AB - An association between otosclerosis and Meniere's disease has been proposed on both a clinical and temporal bone histopathologic basis for well over three quarters of a century. Controversy persists over a causal relationship between these two entities, however, and the underlying pathophysiologic mechanisms relating capsular otosclerosis with Meniere's disease remain speculative. The first case of total, bilateral endolymphatic duct occlusion resulting from extensive capsular otosclerosis is presented in a woman manifesting Meniere's symptoms. The severe endolymphatic hydrops resulting from otosclerotic endolymphatic duct occlusion is given as histopathologic proof of a causal relationship between these two entities. Analysis of 18 of our own temporal bone cases of extensive capsular otosclerosis without endolymphatic hydrops and review of the literature indicates the uniqueness of such a firm causal relationship in the present case. PMID- 2321691 TI - Failure to diagnose acoustic neuroma. PMID- 2321692 TI - Resident-performed stapes surgery. PMID- 2321693 TI - Applications of the KTP laser in chronic ear surgery. AB - Several types of lasers have been applied to otologic surgery for such procedures as laser stapedotomy and acoustic tumor vaporization. The KTP laser has even broader applications in the field of chronic ear surgery. A three and a half year experience with the KTP laser is described. This laser's performance characteristics makes it well suited for chronic ear surgery. A quartz fiber delivery device enables the surgeon hand control of the laser beam in a microscopic field. Several applications are reviewed. Specifically, the KTP laser has been effective in removing hyperplastic infected mucosa engulfing the stapes, in safely disarticulating a mobile stapes suprastructure for complete cholesteatoma removal, and in atraumatically removing previously inserted ossicles or other middle ear implants. The KTP laser enables the surgeon to avoid mechanical trauma possible with traditional instrumentation and obtain more effective disease removal. PMID- 2321694 TI - Embryonic and postnatal development of endolymphatic sac blood vessels. AB - The development of perisaccular blood vessels is described during embryology and the postnatal period of the mouse. Primitive sinusoidal vessels already appear at the early otocyst stage as the future endolymphatic sac is formed. Before birth the vasculature attains a more mature appearance with tubular, somewhat fully developed blood vessels. At this stage a primitive basement membrane is also formed. Soon after birth the blood vessels appear mature with developed fenestrations and micropores, giving them an appearance comparable to blood vessels in other fluid transporting organs. PMID- 2321695 TI - Delayed sensorineural hearing loss following uncomplicated neurovascular decompression of the trigeminal root entry zone. AB - Trigeminal neuralgia (tic douloureux) is a condition characterized by intense, unilateral paroxysmal facial pain caused by an abnormality of the root entry zone of the trigeminal nerve. For patients with intractable pain unrelated to a pathologic process who fail to respond to conventional medical management, the microvascular decompression (MVD) is the operation of choice. Conductive or sensorineural hearing loss due either to stretching of the eighth nerve or hemotympanum during the operation is among the possible sequelae of MVD. We report on a perplexing case of delayed sensorineural hearing loss following uneventful microvascular decompression for trigeminal neuralgia that included intraoperative evoked potential monitoring. PMID- 2321696 TI - Speech perception with the nucleus cochlear implant in children trained with the auditory/verbal approach. AB - Five children between the ages of 6 to 10 years using the Nucleus 22-electrode cochlear implant were tested on a battery of speech-perception tests. None of the five children used any sign language before implantation, and all received extensive training in auditory/verbal rehabilitation postimplantation. Performance ranged from 81 to 97 percent correct on the Matrix Test, from 24 to 80 percent correct on the WIPI test, from 33 to 73 percent correct on a 10-choice vowel recognition test, from 19 to 50 percent correct on a 13-choice consonant recognition test, from 2 to 46 percent words correct on a PB-K word list, from 4 to 71 percent words correct on a recorded BKB sentence test, and from 8 to 71 percent words correct on a live-voice BKB sentence test. In four of the five children, significant lipreading enhancement was observed on consonant recognition and two prelinguistically deafened children demonstrated some open set word recognition. PMID- 2321697 TI - Primary lymphoma of bone. A B-cell neoplasm with a high frequency of multilobated cells. AB - Primary lymphoma of bone is an uncommon neoplasm that can be difficult to diagnose and subclassify. Only in a few cases has the immunophenotype been determined with monoclonal antibodies. We evaluated the histological features and immunophenotype of 12 cases of primary lymphoma of bone. The patients ranged in age from 16 to 80 years (mean, 41 years) with a male:female ratio of 1:1. The sites involved included femur (three cases), humerus (two cases), tibia (three cases), pelvis (two cases), ulna (one case), and scapula (one case). All cases were diffuse large-cell lymphomas: nine large-cleaved (eight with multilobated cells), two large-cell not otherwise specified, and one immunoblastic. Sclerosis was noted in six cases. Immunohistochemical studies on frozen-tissue sections demonstrated staining with the following antibodies: 11 of 11 with CD45, 12 of 12 with CD20, eight of 12 with monotypic immunoglobulin (six IgG, two IgM, seven kappa, one lambda). Tumor cells were negative for T-cell markers in each case. Ten patients are alive and well 0.5-4.5 years (median, 1.5 years) following treatment with radiation or chemotherapy. Two patients had recurrence at another site 0.75 years and 4 years after the initial diagnosis, respectively. Primary bone lymphoma is a B-lineage large-cell lymphoma with an unusually high incidence of large-cleaved and multilobated cells. The frequency of IgG heavy chain expression suggests a post-germinal center stage of differentiation. Frozen section immunohistologic studies are useful in the diagnosis of this tumor. Aggressive therapy has resulted in a favorable outcome in most cases. PMID- 2321698 TI - Intra-abdominal fibromatosis. A pathologic analysis of 130 tumors with comparison of clinical subgroups. AB - We studied the clinical, gross, and histologic findings of 130 fibromatoses of the mesentery and other peritoneal sites. Seventeen patients had Gardner syndrome, 12 had prior abdominal surgery, and six had apparent estrogen elevation, including five pregnant or postpartum women and an alcoholic male with gynecomastia. The tumors were usually large and grossly circumscribed. Most often, they were located in the mesentery of the small bowel. They were multiple in 18 cases. Typical histologic features included a dense, collagenous stroma; prominent, dilated, thin-walled vessels; muscular hyperplasia of small arteries; keloidal change; myxoid change; and fibrous tissue insinuation into the muscularis propria of the bowel. Although mitoses were noted in many tumors, they were usually few in number. The gross and histologic features were similar in the clinical subgroups; however, keloidal change was seen less often in female patients. Less than half of the cases were initially correctly diagnosed. Most patients without Gardner syndrome were without recurrence at follow-up, even when the lesions had been incompletely excised. PMID- 2321699 TI - Ciliated hepatic foregut cyst. A mucus histochemical, immunohistochemical, and ultrastructural study in three cases in comparison with normal bronchi and intrahepatic bile ducts. AB - We describe herein the morphologies of three cases of ciliated hepatic cysts and compare them with those of normal bronchi and intrahepatic bile ducts. Grossly, the hepatic cysts were located in the subcapsular region. They were solitary, unilocular, and rather small (less than 4 cm in diameter). Histologically, the cyst wall consisted of four layers: pseudostratified ciliated columnar epithelia with mucous cells, subepithelial connective tissue, smooth-muscle bundles, and an outermost fibrous capsule. The epithelial cytoplasm contained neutral, carboxylated, and sulfated mucus. We noted moderate immunoreactivity to keratin, epithelial membrane antigen, carcinoembryonic antigen, DU-PAN-2 and secretory component; weak immunoreactivity to cytokeratin CAM 5.2, cytokeratin AE1 + 3, and carbohydrate antigen 19-9; and faint or negative immunoreactivity to IgA and IgM. Cilia were immunoreactive to actin and tubulin; smooth muscles were immunoreactive to actin and desmin. Ultrastructural observations revealed definite cilia arranged in a 9 + 2 pattern as well as mucous cells. These morphologic features of the hepatic cysts were similar to those of normal bronchi but different from those of normal bile ducts. Our findings suggest that ciliated hepatic cysts arise from the embryonic foregut and differentiated toward bronchial structures in the liver. PMID- 2321700 TI - Carcinoma arising in oncocytic Schneiderian papilloma. AB - Two men aged 54 and 73 years, respectively, had oncocytic Schneiderian papilloma (OSP) containing synchronous carcinoma at the time of first biopsy. In both cases, invasive carcinoma involved a small proportion of excised tissue and was in continuity with dysplastic surface epithelium. Our cases document that the epithelial component of OSP can undergo malignant transformation. The focal involvement of OSP with carcinoma underscores the need to examine all excised tissue microscopically. PMID- 2321701 TI - Uterus-like mass of the small intestine. Heterotopia or monodermal teratoma? AB - A 12-year-old girl with multiple lower-intestinal and urogenital tract anomalies and a past history of sacrococcygeal teratoma had an intramural mass of the ileum discovered as an incidental finding at surgery. The predominant mass had the features of the uterine fundus and two smaller contiguous nodules resembled the fallopian tube. A normal uterus and ovaries were observed at surgery. Somewhat similar lesions have been reported in the past in the ovary, ileum, scrotum, and possibly the bladder. Neither the metaplastic nor malformational theories are entirely satisfactory, yet they can be stated for most examples of heterotopias or choristomas. PMID- 2321702 TI - Thymolipoma with striated myoid cells. Histological, immunohistochemical, and ultrastructural study. AB - A large asymptomatic anterior mediastinal thymolipoma, discovered by chest radiograph during a regular check-up for company employees, was excised from a 33 year-old Japanese man. On immunohistochemical and electron-microscopic examination, clusters of myoglobin-positive cells with cytoplasmic Z band structures were found scattered in the medulla. Myoid cells have been previously seen in the normal thymus as well as in thymic hyperplasia, thymoma, and in the thymus of patients with myasthenia gravis. To our knowledge, this is the first reported instance of myoid cells in a thymolipoma. PMID- 2321703 TI - Breast blocks. PMID- 2321704 TI - Nerve sheath versus meningioma. PMID- 2321705 TI - Totally implantable hearing aids: the effects of skin thickness on microphone function. AB - With the advent of totally implantable hearing aids, the question of the impact of the choice of implantation site on microphone function has yet to be fully addressed. We investigated the effects of skin thickness on microphone function over a 2-week period in a porcine model. Sound attenuation was found to be directly proportional to skin thickness within the range of 0.5 to 3.0 mm. A decrease in resonant frequency of 500 Hz was noted after implantation under a skin thickness of 3.0 mm. The general shape of the frequency response curves was maintained across all thicknesses tested. Attenuation (dB loss) across the range of 500 to 8,000 Hz appeared to be linear over the various skin thicknesses measured, with a regression coefficient (r = .99 at 1 kHz and r = .99 at 3 kHz). To minimize attenuation and exploit the sound-collecting qualities of the external ear, the deep meatal skin appears to be a favorable position for implantation. PMID- 2321707 TI - Frequency selectivity in the auditory periphery: similarities between damaged and developing ears. AB - Single fiber tuning curves (stimulus frequency versus neural threshold curves) were obtained from 198 auditory nerve fibers in 24 kittens between birth and the 16th postnatal day and from 74 auditory nerve fibers in adult cats. Three developmental stages during which adult-like frequency-resolving capacity was acquired were identified. During the early stage of postnatal development, all auditory nerve fibers were essentially untuned and responded to a narrow range of low to middle frequency tone bursts presented at intensities exceeding 110 dB sound pressure level (SPL) re 20 muPa. In the intermediate stage, which occurred during the second postnatal week, auditory nerve fibers tuned to low- and mid range frequencies acquired adult-like frequency-resolving capacity. Fibers tuned to high frequencies, which were recorded later in development than those tuned to lower frequencies, were as sharply tuned as their adult counterparts, but exhibited a low contrast between thresholds at characteristic frequency (tip) and lower (tail) frequencies (ie, low tip-to-tail ratios). Adult-like tuning curves were observed during the third stage, primarily as a consequence of the acquisition of adult-like tip-to-tail ratios. Our understanding of the cochlear mechanism(s) by which frequency selectivity is produced in adult animals has recently been enhanced by a combined anatomy and physiology investigation conducted by Liberman and Dodds, in which clear anatomic foci of cochlear damage were identified in cats with functionally characterized hearing loss. Similarly, descriptions of anatomic differentiation in the feline auditory end-organ correlate with functional measures of peripheral auditory system development. In this report, anatomic and physiologic similarities between developing and damaged ears are considered in an attempt to better characterized the process whereby normal frequency selectivities and thresholds are developed. Our findings support the notion that anatomic changes in the cochlea during development, primarily the development of adult-like anatomic relations between the tectorial membrane and sensory cells, underlie the acquisition of adult-like auditory nerve fiber tuning. PMID- 2321706 TI - Pathology and pathogenesis of tympanic membrane retraction. AB - Temporal bones without evidence of otitis media, as well as temporal bones with various types of otitis media, were examined for the presence of retractions of the tympanic membrane and their related histopathologic progression to the formation of cholesteatoma. Retractions were not present in non-otitis media, purulent, or mucoid otitis media. Retractions were observed in 2.1% of temporal bones with serous otitis media and 19.5% of temporal bones with chronic otitis media. All temporal bones with retractions demonstrated evidence of current or previous otitis media. Histopathologic changes of the middle ear cleft were associated with the type and degree of retraction. This study supports the continuum theory according to which otitis media with effusion eventually leads to a variety of sequelae and/or to chronic otitis media. The tympanic membrane appears to follow progressive changes, from simple retraction to retraction pockets and finally to cholesteatoma. PMID- 2321708 TI - Degree of pneumatization of the temporal bone and Meniere's disease: are they related? AB - In 1983, Stahle and Wilbrand examined 63 patients and claimed that there is a correlation between defective pneumatization of the temporal bone, the length of the aqueductus vestibuli, and Meniere's disease. Since our own x-ray and surgical findings did not agree with those of Stahle and Wilbrand, we examined and assessed the pneumatization of the temporal bone volumetrically in 104 patients suffering from Meniere's disease. These examinations took place at the Ear, Nose and Throat Clinic of the University of Essen from 1972 to 1987. For our investigation, we used the method of Gunnel and compared our findings with those of Stahle and Wilbrand, arriving at an almost reverse distribution ratio. From our results, we conclude that a relationship between the degree of pneumatization of the temporal bone and Meniere's disease seems questionable. PMID- 2321709 TI - Lysosomal proteases and protease inhibitors in nasal allergy and non-atopic sinusitis. AB - Patterns of protease activity and levels of protease inhibitors were analyzed in both nasal secretions and tissue extracts from patients with nasal allergy and non-atopic sinusitis to investigate the role of proteases in the inflammatory reaction. Protease activity was measured using specific methyl-coumaryl-7-amide substrates. The pattern of protease activity in the nasal secretions of chronic sinusitis patients was similar to that in neutrophil lysate and quite different from that in plasma. Both gluthatione activation testing and inhibition testing using synthetic inhibitors revealed that the majority of proteases in both secretions and tissues are lysosomal thiol proteases such as cathepsins B and L. Neutrophilic elastase is also a major protease in nasal secretions. In acute sinusitis, both protease activity and inhibitor levels were very high, suggesting an interaction between proteases and inhibitors. Cathepsin B and B-like thiol proteases appear to play a key role in prolonging chronic inflammation against the healing process, due to their resistance to plasma inhibitors and the shortage of thiol protease inhibitors. Protease activity in the secretions of nasal allergy patients was very weak, and the reaction between proteases and inhibitors appeared to be weak. PMID- 2321711 TI - Clinical radiology quiz. PMID- 2321710 TI - The effect of isotretinoin on propylene glycol-induced cholesteatoma in chinchilla middle ears. AB - Previous studies have shown that propylene glycol causes inflammatory changes and cholesteatoma when applied to chinchilla middle ears. Vitamin A and synthetic analogues are essential for the normal differentiation of epithelial tissues. The purpose of this study was to determine whether the administration of isotretinoin to chinchillas would prevent propylene glycol exposure from inducing middle ear cholesteatomas. Sixteen chinchillas received 90% propylene glycol to the left middle ear and normal saline to the right. Half the animals were placed in the experimental group and received a daily dose of isotretinoin of 2 mg/kg for 7 days prior to propylene glycol administration and then for 6 weeks until killed. At 6 weeks, cholesteatoma was found in six of eight ears treated with propylene glycol in animals receiving isotretinoin. Two animals in the control group died. Three of the remaining eight had cholesteatoma. No ears treated with saline had cholesteatoma. We conclude that isotretinoin, in our chinchilla model, does not prevent propylene glycol-induced cholesteatoma formation. PMID- 2321712 TI - Delayed detection of hypoxic events by pulse oximeters: computer simulations. AB - There is a variable delay between a reduction in alveolar PO2 and the decrease in arterial oxygen saturation recorded on a pulse oximeter. The decrease in arterial oxygen saturation in response to disconnexion of a paralysed patient from the breathing system, oxygen supply failure with continued mechanical ventilation and disconnexion of the fresh gas supply to Mapleson D and circle absorption breathing systems were studied by simulations on the MacPuf computer model of the cardiorespiratory system. The simulations revealed that there were marked differences between the rate of arterial desaturation which resulted from each of the three types of oxygen supply failure and that arterial oxygen saturation may reach dangerous levels before a pulse oximeter alarm is activated. PMID- 2321713 TI - Lytic cocktail in children. Rectal versus intramuscular administration. AB - The efficacy of the lytic cocktail (1 ml contains pethidine 28 mg, promethazine 7 mg, chlorpromazine 7 mg) administered intramuscularly or rectally as premedication was studied in 51 children aged 1-12 years who had minor elective otological surgery. One group received 0.05 ml/kg intramuscularly (maximum dose 2.0 ml) and the other 0.07 ml/kg per rectum (maximum dose 2.8 ml). Most were satisfactorily sedated before operation, but after operation the rectally premedicated children were less sedated, which was in agreement with lower plasma pethidine concentrations in this group. The rectal dose should be increased if prolonged postoperative sedation is desireable. PMID- 2321714 TI - Malignant hyperthermia during isoflurane anaesthesia. AB - Two cases are presented which illustrate the essential features, diagnosis and management of malignant hyperthermia. Both cases occurred in association with isoflurane, and in patients who were exposed during previous anaesthetics to recognised trigger agents without apparent manifestation of the syndrome. PMID- 2321715 TI - Anaesthesia in a gravid achondroplastic dwarf. AB - A patient with achondroplasia presented for elective Caesarean section under epidural anaesthesia. A block from C5 to S4 developed over 20 minutes after 12 ml plain bupivacaine 0.5%. This case serves to highlight the difficulties of regional anaesthesia in the gravid achondroplastic dwarf. PMID- 2321716 TI - An unusual presentation of cardiac tamponade. AB - A case of pericardial effusion with tamponade that presented as an acute abdomen is described. PMID- 2321717 TI - Hypotension due to unexpected cardiac tamponade. AB - We report a case of profound hypotension, after induction of general anaesthesia, that resulted from unexpected cardiac tamponade. The differential diagnosis was complicated by the absence of any evidence to indicate that there was significant direct chest injury. Many of the recognised clinical signs of cardiac tamponade were absent, in particular, there was no compensatory tachycardia, and heart rate remained stable despite severe hypotension before surgical drainage of the pericardium. The possible aetiology and pathophysiology is discussed. It is suggested that after major trauma, cardiac tamponade should be considered as a possibility even in the absence of significantly abnormal cardiovascular signs, evidence of direct chest injury, or an abnormal chest X ray. PMID- 2321718 TI - Continuous brachial plexus blockade. A technique that uses an axillary catheter to allow successful skin grafting. AB - An 82-year-old woman sustained a full thickness burn of her hand. A technique for producing anaesthesia of the brachial plexus via an indwelling catheter is described. Confirmation of the catheter position was obtained by X ray. Bupivacaine was infused via the catheter after operation to produce immobilisation of the hand to ensure multiple skin grafts would take. Consequent with this goal was excellent postoperative analgesia. PMID- 2321719 TI - Equipment deadspace and drug administration. AB - Equipment deadspace can be a hazard in drug administration. The aim of this study was to measure the size of this problem. The deadspaces of a selection of cannulae, syringes and epidural catheters were measured by displacing the deadspace volume with water and measuring the weight gain. Between 10 and 30% of a 1-ml intravenous dose will remain in the deadspace depending on the type and gauge of the cannulae. The deadspace of an epidural catheter and filter is approximately 1 ml. All cannulae should be flushed after drug administration. Epidural catheters must be flushed with the same solution as the test dose before insertion. PMID- 2321720 TI - The nature of pre-operative anxiety. AB - In a study of 247 patients who had general anaesthesia for dental procedures, the incidence of individual anxieties was noted using a questionnaire completed by the patient. The most common anxieties related to the period before transfer to the operating theatre, intra-operative awareness and postoperative pain. These anxieties were present in over half the patients questioned. The follow-up questionnaire was completed by 207 patients in order to indicate which anxieties they would expect to have if they needed anaesthesia in the future. All anxieties were less frequent than found before operation. PMID- 2321721 TI - Paediatric postoperative analgesia. A comparison of rectal diclofenac with caudal bupivacaine after inguinal herniotomy. AB - Forty-three children for day case inguinal herniotomy under general anaesthesia were assigned randomly to receive either 1 ml/kg caudal bupivacaine 0.25% or rectal diclofenac 0.25 mg/kg intra-operatively to provide postoperative analgesia. Pain and demeanour were assessed by an observer in the early postoperative period after operation and by questionnaire for the parents over the first 24 hours. Caudal bupivacaine provided more pain-free patients at first but later the incidence of pain was similar in the two treatment groups. Rectal diclofenac is a useful alternative to caudal blockade in this group of patients. PMID- 2321722 TI - Caesarean section: pain and awareness without negligence. PMID- 2321723 TI - Femoral nerve block after intra-operative subcutaneous bupivacaine injection. PMID- 2321724 TI - Propofol for caesarean section. PMID- 2321725 TI - A dangerous failure of a pulse oximeter. PMID- 2321726 TI - Atracurium and hypoxaemic episodes. PMID- 2321727 TI - The laryngeal mask: cautionary tales. PMID- 2321728 TI - The laryngeal mask and difficult tracheal intubation. PMID- 2321729 TI - Diabetes and hypotension. PMID- 2321730 TI - The management of hyponatraemia. PMID- 2321731 TI - Another cause for bradycardia during neurosurgery. PMID- 2321732 TI - Epidural analgesia and hypotension. PMID- 2321733 TI - Comparison of anxiety before induction of anaesthesia in the anaesthetic room or operating theatre. PMID- 2321734 TI - Bain and circle systems. PMID- 2321735 TI - Pneumothorax caused by minitracheostomy. PMID- 2321736 TI - Kinked breathing systems. PMID- 2321737 TI - Pain in the neck. PMID- 2321738 TI - Cost awareness among junior anaesthetists. PMID- 2321739 TI - The costs of propofol in day surgery. PMID- 2321740 TI - Blackout during cardiopulmonary bypass. PMID- 2321741 TI - Heparin and heparin-saline: another hazard. PMID- 2321742 TI - A paediatric orotracheal tube with laryngeal hooks. PMID- 2321743 TI - Failure of oxygen flush device. PMID- 2321744 TI - The sterility of lubricant jelly used on tracheal tubes. PMID- 2321745 TI - Noncyclooxygenase oxidative formation of a series of novel prostaglandins: analytical ramifications for measurement of eicosanoids. AB - Analysis of fresh plasma from normal volunteers by negative ion chemical ionization GC/MS reveals what appear to be multiple PGF2 compounds with levels ranging from approximately 5 to 40 pg/ml. Interestingly, storage of plasma at -20 degrees C for several months was found to markedly increase the levels of these compounds to about 1000-4000 pg/ml, approximately 50-fold higher than levels detected in fresh plasma. Further studies aimed at understanding this observation revealed that alkaline hydrolysis of plasma lipids also yielded quantities of these compounds in the range that were detected in stored plasma. Employing a number of approaches such as deuteriated derivatives, hydrogenation, immunoreactivity with an anti-9 alpha, 11 beta-PGF2 antibody, and electron ionization mass spectral analysis, convincing evidence was obtained that these compounds in both stored and base-treated plasma were in fact PGF2 compounds. Formation of these compounds was found to occur by a nonenzymatic oxidative process in that the antioxidant, butylated hydroxytoluene, and the reducing agent, triphenylphosphine, markedly suppressed their formation. Evidence is presented to support a proposed mechanism that oxidative formation of these compounds involves the formation of endoperoxide intermediates which are directly reduced by naturally occurring biological substances to PGF2 compounds. Formation of these compounds occurs very readily in biological fluids. This finding has important ramifications not only for analysis of enzymatically derived PGF2 compounds but also for other eicosanoids which can be formed by this same nonenzymatic process. These analytical concerns apply to both immunoassay methods and physical methods of analysis such as gas chromatography/mass spectrometry. PMID- 2321746 TI - Adaptation of an enzymatic cycling assay for NADP(H) measurement to the COBAS FARA centrifugal analyzer. AB - NADP(H) measurements by enzymatic amplification are described in which the interface step between cycling (glucose-6-phosphate and glutamic dehydrogenases) and indicator (6-phosphogluconic dehydrogenase) enzymes has been reconfigured, permitting the entire operation to run as a continuous assay on a centrifugal fast analyzer. This is accomplished by using the sequential load feature of the analyzer and incorporating either sodium dodecyl sulfate (SDS) or SDS and hydrogen peroxide as kill reagents to replace the thermal step (destruction of cycle enzymes by boiling). The ability of SDS to render a cycle inoperative during the run time of the indicator enzyme depends on the inherent resistivity and absolute amount of its enzyme proteins to this surfactant. Criteria used to judge the efficacy of a potential kill reagent are based on the sample blank time response curve and the cycle product recovery by the indicator enzyme. Various other enzyme cycling systems which can be fitted to the centrifugal fast analyzer are highlighted. PMID- 2321747 TI - Increased uniformity in the response of the coomassie blue G protein assay to different proteins. AB - Coomassie blue G dye-based protein assays are exceptionally convenient because of their simplicity, sensitivity, speed, and resistance to interfering chemicals, notably reducing agents and most buffers. A major problem with the assay is the variation in response to different proteins. The addition of NaOH to the protein assay reagent reduced the variation in the response of this assay to different proteins. In addition, the sensitivity of the assay is increased. The NaOH can be added either in a separate step to solubilize cells or membranes or directly to the reagent. Linear standard curves were obtained when the log of the absorbance was plotted against the log of the protein quantity. PMID- 2321748 TI - A method for binding parameters estimation of A1 adenosine receptor subtype: a practical approach. AB - Working with pig brain striatum in which A1 and A2 adenosine receptor subtypes coexist, we describe an uncomplicated method for unequivocally obtaining the equilibrium parameters (KD and binding capacity) of A1 receptor without interference from ligand binding to A2 receptor. Also, the equilibrium parameter estimation method we propose avoids the experimental determination of nonspecific binding by the inclusion of the corresponding unknown parameter in the function. This not only saves time but also avoids the use of expensive radioligands in saturation experiments. The method is suitable for any system with two different receptor subtypes for the same physiological ligand, and good estimates of the equilibrium parameters corresponding to the subtype displaying the higher affinity for the ligand can be obtained. PMID- 2321749 TI - A fiberoptic cholesterol biosensor with an oxygen optrode as the transducer. AB - A biosensor for the continuous optical determination of cholesterol is presented. Cholesterol oxidase is immobilized covalently on a nylon membrane and the consumption of oxygen is measured by following, via fiberoptic bundles, the changes in fluorescence of an oxygen-sensitive dye whose fluorescence is dynamically quenched by molecular oxygen. The dye is dissolved in a very thin silicone membrane placed beneath the enzyme layer. During interaction of the enzyme with cholesterol, oxygen is consumed, which is indicated by the fluorescent dye. At pH 7.25, the analytical range of the sensor is 0.2 to 3 mM and the time to reach a full steady state in a flowing solution ranges from 7 to 12 min. PMID- 2321750 TI - Estimation of elution times on reverse-phase high-performance liquid chromatography of pyridylamino derivatives of sugar chains from glycoproteins. AB - Addition of a sugar residue to a pyridylamino (PA) sugar chain affects its elution time on reverse-phase HPLC and the contribution of the sugar residue is not influenced by the other sugar residues [S. Hase, S. Natsuka, H. Oku, and T. Ikenaka (1987) Anal. Biochem. 167, 321-326]. The partial relative elution times (Ei) of 22 sugar residues were calculated from the relative elution times (the elution time relative to Man5Glc-NAc2-PA) of three kinds of PA-sugar chain: the oligomannose and N-acetyllactosamine types and sugar chains with a xylose residue. The relative elution time of a PA-sugar chain can be calculated by summing the Ei values of all of the constituent sugar residues. The calculated relative elution times of 44 PA-sugar chains agreed well with the observed values. This method can be used to estimate the relative elution times of PA sugar chains that are not yet available, and to estimate the structures of sugar chains in limited amounts of glycoproteins by a combination of sugar composition analysis and exoglycosidase digestion. PMID- 2321751 TI - Analysis of derivatized ceramides and neutral glycosphingolipids by high performance tandem mass spectrometry. AB - Microscale reduction of ceramides and neutral glycosphingolipids has been evaluated as a means of improving their analysis by fast atom bombardment mass spectrometry, alone and in combination with tandem mass spectrometry. Reduction (conversion of the amide to an amine) of native ceramides and glycosphingolipids containing one to three sugars yields derivatives that show significant signal enhancement. This sensitivity increase allows the acquisition of normal and tandem fast atom bombardment mass spectra from a submicrogram amount of sample. Concomitant permethylation is required for glycosphingolipids that contain more than three sugars. Collision induced dissociation mass spectra of protonated molecular ions, recorded on a four sector instrument, show improved fragmentation allowing the simultaneous characterization of both the ceramide and carbohydrate portions of glycosphingolipids. The reductions are carried out at the nanogram to microgram level with borane, reacting the solid sample with condensed reagent vapor. The borane reduction method has been adapted for this class of substances by adding an oxidation step in order to convert unsaturated lipids to hydroxylated derivatives by oxidation of the resulting organoborane. This approach, used in conjunction with tandem mass spectrometry, allows the determination of olefinic bond location. Labeled derivatives have been prepared by reacting the substrates with trideuterioborane and were used to ascertain the fragmentations and localize olefinic bonds. The collision induced fragmentation of reduced ceramides and neutral glycosphingolipids is only weakly affected by the presence of additional functionalities, such as methoxyl (after permethylation) and hydroxyl groups (resulting from hydroboration and oxidation), a characteristic which facilitates interpretation of the spectra of unknown compounds. PMID- 2321752 TI - A dual streaming potential device used as an affinity sensor for monitoring hybridoma cell cultivations. AB - A dual streaming potential device was used for determining the content of monoclonal antibodies in cultivation medium for hybridoma cells. Samples of culture medium were analyzed as discrete pulses, as a continuous flow of constant concentration as well as with fluctuating concentrations. Tests were done with two subclasses of IgG as well as with IgM. Finally, the analytical device was applied to the registration of production of monoclonal antibodies in a cultivation. PMID- 2321753 TI - DESIGN: computerized optimization of experimental design for estimating Kd and Bmax in ligand binding experiments. II. Simultaneous analysis of homologous and heterologous competition curves and analysis blocking and of "multiligand" dose response surfaces. AB - We have developed a computer program, DESIGN, for optimization of ligand binding experiments to minimize the "average" uncertainty in all unknown parameters. An earlier report [G. E. Rovati, D. Rodbard, and P. J. Munson (1988) Anal. Biochem. 174, 636-649] described the application of this program to experiments involving a single homologous or heterologous dose-response curve. We now present several advanced features of the program DESIGN, including simultaneous optimization of two or more binding competition curves optimization of a "multiligand" experiment. Multiligand designs are those which use combinations of two (or more) ligands in each reaction tube. Such designs are an important and natural extension of the popular method of "blocking experiments" where an additional ligand is used to suppress one or more classes of sites. Extending the idea of a dose-response curve, the most general multiligand design would result in a "dose response surface". One can now optimize the design not only for a single binding curve, but also for families of curves and for binding surfaces. The examples presented in this report further demonstrate the power and utility of the program DESIGN and the nature of D-optimal designs in the context of more complex binding experiments. We illustrate D-optimal designs involving one radioligand and two unlabeled ligands; we consider one example of homogeneous and several examples of heterogeneous binding sites. Further, to demonstrate the virtues of the dose response surface experiment, we have compared the optimal surface design to the equivalent design restricted to traditional dose-response curves. The use of DESIGN in conjunction with multiligand experiments can improve the efficiency of estimation of the binding parameters, potentially resulting in reduction of the number of observations needed to obtain a desired degree of precision in representative cases. PMID- 2321754 TI - Spectrophotometric quantitation of anchorage-dependent cell numbers using the bicinchoninic acid protein assay reagent. AB - A rapid and convenient method is described for the determination of the actual and relative number of adherent cells in tissue culture. The cell lines human melanoma C32, ATCC CRL 1585, mouse melanoma B16-F10, and pig epithelial LLC-PK1, suspended in Dulbecco's minimum essential medium containing no serum, were allowed to adhere to fibronectin adsorbed to wells of a 96-well microtiter plate. Nonadherent cells were removed by aspiration, wells were washed, and adherent cells were solubilized with 200 microliters of the bicinchoninic acid (4,4' dicarboxy-2,2'-biquinoline) protein assay reagent. Plates were heated to 60 degrees C for 30 min and absorbances read at 562 nm using a microtiter plate reader. A linear correlation was observed between the number of adherent cells in the range 2-8 X 10(5)/ml cells added and the protein content of the adherent cells as measured by the BCA protein reagent. The assay procedure gave absorbance values in the range of 0.100 to 1.30 making the method highly sensitive and reproducible. Blank wells containing only coupled protein and no cells gave little or no absorbance. Cell adhesion was fibronectin specific since little or no cell attachment was observed when microtiter plates were coupled with bovine serum albumin. Similar results were obtained with other cell types such as platelets. These results indicate that measurement of total cellular protein using the BCA protein reagent can be a rapid and sensitive assay for the detection and quantitation of adherent cells. PMID- 2321756 TI - Identification of methionine-containing tryptic peptides of unstable beta-tubulin separated by reverse-phase high-performance liquid chromatography. AB - Methods for examining altered regions in unstable mutant proteins are described. The strategy is illustrated using assembly defective Chinese hamster beta-tubulin subunits that are rapidly degraded in the cell. These unstable proteins are metabolically labeled to high specific activity and isolated as spots on two dimensional gels. Conditions for the generation of tryptic peptides from gel pieces containing beta-tubulin and their subsequent resolution by HPLC have been worked out. Through a combination of dual labeling with various tritiated amino acids and [35S]methionine as well as partial sequence analysis, the identification of several HPLC peaks with the known sequence of beta-tubulin has been accomplished. This technique should greatly aid attempts to map the sites of mutational alterations in beta-tubulin polypeptides, and the general strategy should be readily applicable to other mutant proteins. PMID- 2321755 TI - Comparison of a spectrophotometric, a fluorometric, and a novel radiometric assay for carboxypeptidase E (EC 3.4.17.10) and other carboxypeptidase B-like enzymes. AB - Carboxypeptidase E (CPE) is a carboxypeptidase B-like enzyme involved in the biosynthesis of numerous peptide hormones and neurotransmitters. A sensitive assay for CPE and other carboxypeptidase B-like enzymes has been developed using 125I-acetyl-Tyr-Ala-Arg (125I-AcYAR) as the substrate. This peptide is poorly soluble in ethyl acetate whereas the product of carboxypeptidase B-like enzymatic activity (125I-AcYA) can be quantitatively extracted with this solvent, allowing the rapid separation of product from substrate. This radiometric assay can detect less than 1 pg of either CPE or carboxypeptidase B. For CPE, the assay with 125I AcYAR is approximately 1000 times more sensitive than a fluorescent assay using dansyl-Phe-Ala-Arg (dans-FAR), and 6000 times more sensitive than a spectrophotometric assay using hippuryl-Arg (hipp-R). CPE hydrolyzes the three substrates with Kcat values of 16 s-1 for AcYAR, 13 s-1 for dans-FAR, and 8.5 s-1 for hipp-R. The Km values for CPE with AcYAR (28 microM) and dans-FAR (34 microM) are similar, and are much lower than the Km with hipp-R (400 microM). Thus, the primary reason for the increased sensitivity of the 125I-AcYAR assay over the fluorescent assay is not a result of kinetic differences but is due to the detection limit of iodinated product (10(-15) mol), compared to the fluorescent product (5 x 10(-11) mol). Applications of this rapid and sensitive radiometric assay to detect CPE in cultured cells and in subcellular fractions of the pituitary are described. PMID- 2321757 TI - The determination of the Mg2+.ATP dissociation constant by competition with Eu3+ ion using laser-induced Eu3+ ion luminescence spectroscopy. AB - A direct spectroscopic method for the determination of the submicromolar dissociation constant of Eu3+. ATP using laser-induced Eu3+ ion luminescence spectroscopy is described. The dissociation constant of Mg2+.ATP is then determined by the competition of Mg2+ with Eu3+ for the binding of ATP. The experiments were performed in 2H2O to mitigate the significant quenching of the Eu3+ luminescence that occurs in 1H2O. Values for the effective dissociation constants of the 1:1 ATP metal ion complexes of 1.2 +/- 0.3 X 10(-7) and 2.7 +/- 0.7 X 10(-4) M are obtained for Eu3+ and Mg2+, respectively, at p2H 5.8. PMID- 2321758 TI - Determination of aconitate isomerase in plants. AB - We have developed a method for measuring aconitate isomerase (EC 5.3.3.7) in plants which depends on the release of tritium from labeled trans-aconitate. The released tritium is separated from labeled aconitate by passage through a column of strong anion-exchange resin. This method is more sensitive, simpler, and more specific than previous methods, especially with crude extracts. The validity of the method was demonstrated by a comparison of the quantity of tritium released with the amount of cis-aconitate isomerized and this comparison demonstrated an isotope effect. Aconitase did not interfere. The method was tested by measuring aconitate isomerase in crude extracts of several higher plant species and tissues and these analyses showed that wheat and corn have more aconitate isomerase than the other species tested. PMID- 2321759 TI - A radiometric kynurenine monooxygenase assay. AB - Kynurenine 3-monooxygenase is a flavin-dependent monooxygenase that catalyzes the oxidation of L-kynurenine to 3-hydroxy-L-kynurenine in the kynurenine pathway of tryptophan metabolism. The enzyme requires NADH or NADPH as a cofactor. A discontinuous assay that utilizes L-[3H]kynurenine as substrate is described. The assay offers high precision and a wide range of accessible substrate and cofactor concentrations. The assay was used to measure kinetic isotope effects and the stereospecificity of oxidation of the cofactor. Hydride is transferred from the A side (pro-R) of NADH and NADPH since primary deuterium isotope effects were observed for both cofactors when they were deuterated on the A-side but not on the B-side. The large isotope effect on Vmax/Km for NADH is sensitive to the concentration of kynurenine, which indicates that NADH can bind before kynurenine. PMID- 2321760 TI - Synthesis of nucleic acid probes on membrane supports: a procedure for the removal of unincorporated precursors. AB - We have used DNA bound to small pieces of nylon membrane for the synthesis of radioactive probes. The DNA to be used for generating the probe(s) is first bound to nylon membranes and then introduced into the reaction mix. The labeling reaction takes place on the membrane and therefore allows easy removal of unincorporated precursors by simple washing for 1-2 min. The clean labeled probe is eluted from the membrane in formamide or in water and is ready for use. This DNA-membrane can be stored for reuse. Synthesis of probes on a solid support such as nylon membrane thus circumvents problems associated with chromatographic manipulations needed for the separation of labeled DNA from unicorporated precursors. Probes synthesized in this manner are as efficient in detecting nucleic acid sequences as those synthesized in solution. PMID- 2321761 TI - Calculation of subunit stoichiometry of large, multisubunit proteins from amino acid compositions. AB - The subunit stoichiometry of a large, multisubunit protein can be determined from the molar amino acid compositions (i amino acids) of the protein and its subunits. The number of copies of the subunits (1, 2, ... j) is calculated by solving all possible combinations of simultaneous equations in j unknowns (i!/j!(i - j)!). Calculations carried out using the published amino acid compositions determined by analysis and the compositions calculated from the sequences for two proteins of known stoichiometry provided the following results: Escherichia coli aspartate transcarbamoylase (R6C6, Mr = 307.5 kDa), R = 5.6 to 6.6 and C = 5.8 to 6.3, and spinach ribulose-bisphosphate carboxylase (L8S8, Mr = 535 kDa), L = 7.3 to 9.1 and S = 5.6 to 10.6. Calculations were also carried out with the amino acid compositions of two much larger proteins, the E. coli pyruvate dehydrogenase complex, Mr = 5280 kDa, subunits E1 (99.5 kDa), E2 (66 kDa), and E3 (50.6 kDa), and the extracellular hemoglobin of Lumbricus terrestris, Mr = 3760 kDa, subunits M (17 kDa), D1 (31 kDa), D2 (37 kDa), and T (51 kDa); the results for PDHase were E1 = 20 to 24, E2 = 18 to 31, E3 = 21 to 33 and those for Lumbricus hemoglobin were M = 34 to 46, D1 = 13 to 19, D2 = 13 to 18, and T = 34 to 36. Although the sample standard deviations of the mean values are generally high, the proposed method works surprisingly well for the two smaller proteins and provides physically reasonable results for the two larger proteins. PMID- 2321762 TI - High-performance liquid chromatographic determination of beta-phenylethylamine in human plasma with fluorescence detection. AB - A simple and highly sensitive method for the determination of beta phenylethylamine in human plasma is investigated. The method employs high performance liquid chromatography with fluorescence detection. beta Phenylethylamine and p-methylbenzylamine (internal standard) in human plasma are isolated by cation-exchange chromatography on a Toyopak SP cartridge and then converted into the corresponding fluorescent derivatives with 3,4-dihydro-6,7 dimethoxy-4-methyl-3-oxoquinoxaline-2-carbonyl chloride, a fluorescence derivatization reagent for amines. The derivatives are separated within 30 min on a reversed-phase column, TSK gel ODS-120T, with isocratic elution, and detected fluorometrically. The detection limit of beta-phenylethylamine is 0.3 pmol/ml in plasma (S/N = 3). PMID- 2321763 TI - Optimization of northern analysis by vacuum-blotting, RNA-transfer visualization, and ultraviolet fixation. AB - We have optimized Northern analysis at several steps. Overnight electrophoresis was replaced by short gel runs and overnight capillary transfer by rapid vacuum blotting adapted to Northern analysis. Short uv irradiation was used as a substitute for the usual RNA fixation by baking. Direct staining of RNA before electrophoresis made it possible to check RNA integrity and to evaluate the quality of the size separation immediately after electrophoresis. In this system, RNA transfer onto the membrane support could also be quickly assessed after the blotting step. The net result of all modifications was a doubling of the autoradiography signal compared with that obtained by modern Northern protocols. At the same time, the duration of the procedure was shortened drastically, allowing an autoradiography signal to be obtained within 24 h. PMID- 2321764 TI - Detection of hemoprotein peroxidase activity on polyvinylidene difluoride membrane. AB - The feasibility of detecting hemoproteins after electroblotting was examined. Hemoproteins were subjected to lithium dodecyl sulfate-polyacrylamide gel electrophoresis (LDS-PAGE) and then electroblotted and peroxidase activity was detected with 3,3',5,5'-tetramethylbenzidine The sensitivity and specificity of tetramethylbenzidine staining of LDS-PAGE gels was retained when proteins were electroblotted. Subsequent staining of the membrane with Coomassie blue R-250 revealed a protein pattern similar to that in the polyacrylamide gel. Thus electroblotting of hemoproteins does not affect resolution of the electrophoretic pattern and heme-associated peroxidase activity. Additionally, the ability to stain hemoproteins on polyvinylidene difluoride membranes offers the advantage of utilizing the same membrane for further biochemical and immunological characterizations. PMID- 2321765 TI - Rapid analysis of polyolefin antioxidants and light stabilisers by supercritical fluid chromatography. AB - Nineteen commercial antioxidants and light stabilisers, with a wide range of relative molecular masses and boiling-points, present in polyolefins were analysed by packed column supercritical fluid chromatography on four different phases with CO2 or 10% MeOH-CO2 as the mobile phase and with UV detection. The technique is shown to yield short analysis times and sufficient resolution for a number of additives present in a given polyolefin. PMID- 2321766 TI - High-performance liquid chromatographic determination of ochratoxin A and its 4R 4-hydroxy metabolite in human urine. AB - One of the metabolites of ochratoxin A (OA) is 4R-4-hydroxyochratoxin A (4-OH OA), and the ratio of 4-OH-OA to OA excreted in urine can be linked to the carcinogenic potential of this compound. As further support to the hypothesis that OA can be involved in Balkan endemic nephropathy and the associated urinary system tumours, it was decided to investigate the presence of these two compounds in the urine of affected populations. A sensitive method is described for the determination of the compounds at the 10 ng l-1 level. It involves extraction, two purification steps by column chromatography and high-performance liquid chromatography (HPLC), an analysis by HPLC and a confirmatory test by HPLC after derivatisation. PMID- 2321767 TI - Monitoring and confirming primary alkylamines via a simple derivatisation procedure. AB - Carbon disulphide reacts readily with primary alkylamines to yield dithiocarbamates. When injected into the heated injection port of a gas chromatograph, the dithiocarbamates yield the corresponding isothiocyanates. This reaction provides a simple and elegant derivatisation for quantifying, and also confirming the identify of, the primary alkylamines. PMID- 2321769 TI - Digestion method for the determination of mercury in vegetable matrices by cold vapour atomic absorption spectrometry. AB - A simple and rapid wet-digestion procedure is described for the determination of total mercury in botanical samples by cold vapour atomic absorption spectrometry. The method is based on the oxidising properties of potassium dichromate in dilute sulphuric acid and was tested on two National Institute of Standards and Technology Standard Reference Materials. The mass of the samples taken for analysis was about 0.5 g in all instances, corresponding to an amount of mercury of the order of 0.075-0.040 micrograms depending on the material. The results were compared with those obtained using the Association of Official Analytical Chemists official digestion technique, which involves the use of nitric and sulphuric acids, and a second technique based on the action of nitric and perchloric acids. The proposed method provided better accuracy and showed good precision. Its ability to achieve the decomposition of two organomercurials for full mercury recovery was verified. PMID- 2321768 TI - Chemical transduction with fluorescent lipid membranes using selective interactions of acetylcholine receptor with agonist/antagonist and acetylcholine with substrate. AB - Alterations in the physical structure of vesicles and monolayers of phospholipids and soybean lecithin were monitored by measurement on the average fluorescence intensity changes from N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)dipalmitoyl-L-a phosphatidyl ethanolamine (NBD-PE) located in the lipid matrices. This probe was intimately dispersed at a concentration of 1-2 mol-% in lipid membranes and had an emission sensitive to local environmental structure. Alterations in the structure of soybean lecithin vesicles were induced by the selective interaction of acetylcholine receptor with the agonist carbamylcholine and the antagonist alpha-bungarotoxin. Structural changes in vesicles with a 7:3 mole ratio of dipalmitoylphosphatidyl choline to dipalmitoylphosphatidic acid were observed for selective interactions between acetylcholinesterase and acetylcholine. Enhancement of fluorescence emission from the lipid membranes provided transduction of the selective binding events of the receptor and enzyme. A maximum sensitivity of about a 30% enhancement per micromole of carbamylcholine and a detection limit for the toxin of 10 nM were observed for the receptor. Fluorescence microscopy was used to establish that protein could be incorporated in monolayer lipid membranes and to provide information about potential mechanisms of fluorescence enhancement. These studies show that lipid membranes containing NBD-PE can be used as generic transducers of protein-ligand interactions. PMID- 2321770 TI - Method for determining paracetamol in whole blood by chronoamperometry following enzymatic hydrolysis. AB - A method is proposed for the determination of paracetamol in whole undiluted blood, based on the enzymatic hydrolysis of the drug to p-aminophenol, which is then measured by chronoamperometry at a glassy carbon electrode. Hydrolysis of the paracetamol prior to electro-oxidation is shown to alleviate problems that arise from high background currents in the whole blood and so ensures a good linear correlation (r greater than 0.99) between the current and the paracetamol concentration. Recovery experiments and comparison with a reference method based on spectrophotometry suggest that the electrochemical assay only measures that proportion of paracetamol that is not bound to serum albumin. PMID- 2321771 TI - Voltammetric assay of heroin in illicit dosage forms. AB - The oxidation of heroin on a carbon paste electrode has been studied by using voltammetric techniques under both semi-infinite linear diffusion and hydrodynamic conditions. By employing a simple and rapid in situ pre-treatment of the electrode, excellent reproducibility of the current signal was obtained. Subsequently, the current was measured and the concentration of total heroin present could be determined. The method compared favourably with instrumental methods that are more commonly used for the quantification of heroin in clinical laboratories such as chromatographic, spectrophotometric or radiometric techniques. Moreover, the proposed method showed good selectivity and was superior with respect to cost and time of analysis, permitting the determination of heroin in seized drug samples over a wide concentration range. PMID- 2321772 TI - Ingestion of liquids compared with preoperative fasting in pediatric outpatients. AB - The preoperative fast is often an unpleasant preoperative experience that might be alleviated by allowing children to drink clear liquids. The authors compared gastric fluid volume and pH in two groups of children, one of whom was permitted clear liquids until 2 h before surgery (study group) and the other followed routine preoperative fasting orders (control group). The study group was not limited in the quantity of clear liquid allowed with the exception that the last intake prior to surgery was limited to 8 ounces. The study group (n = 53) averaged 5.9 +/- 5 yr and weighed 23.6 +/- 17 kg, while the control group averaged 7.3 +/- 4.6 yr and weighed 29 +/- 17.7 kg (P = NS). Gastric contents were aspirated following induction of anesthesia. Gastric fluid volume averaged 0.44 +/- 0.51 ml/kg for study group and 0.57 +/- 0.51 ml/kg in the control group (P = 0.12). Of the study patients, 48% had a measured gastric fluid volume greater than or equal to 0.4 ml/kg compared with 58% of the control patients (P = 0.77). Eighty three patients had sufficient gastric fluid for pH determination; of these 34/35 (97%) in the study group and 44/48 (92%) in the control group had a gastric fluid pH less than or equal to 2.5. Using a linear analog scale parents rated the children in the study group to be less irritable (P less than 0.001) and to have had a better overall preoperative experience (P less than 0.01) compared with the control patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321773 TI - Oliguria in patients with normal renal function. AB - Oliguria is common in critically ill patients and may result from prerenal, renal, and postrenal causes. Oliguria also frequently develops in patients with normal concentrations of blood urea nitrogen and creatinine. Most of these patients do not develop renal failure. The authors prospectively studied 100 patients admitted to the ICU to determine the etiology of oliguria in these patients. Eighteen patients (18%) developed oliguria (less than 0.33 ml.kg-1.h-1 X 2 h). Seven and eleven patients were felt on clinical assessment to be hypovolemic or normovolemic, respectively. Compared with the hypovolemic patients, the normovolemic oliguric patients had significantly lower serum osmolalities (278 +/- 3 vs. 290 +/- 5 mOsm/kg H2O) and serum sodium concentrations (138 +/- 3 vs. 132 +/- 1 mEq/l). In addition, normovolemic patients had significantly higher urine sodium concentrations (83 +/- 12 vs. 13 +/- 2 mEq/l), fractional excretion of sodium (1.14 +/- 0.2 vs. 0.15 +/- 0.03), and renal failure indices (1.5 +/- 0.3 vs. 0.21 +/- 0.04). ADH concentrations in six hypovolemic and six normovolemic patients were increased in both groups but not significantly different. The hypovolemic patients increased their urine output from 17 +/- 2 ml/h to greater than 0.5 ml.kg-1.h-1 following a 500-ml bolus of normal saline. The normovolemic oliguric patients remained oliguric following the saline bolus (13 +/- 2 to 19 +/- 3 ml/h). The authors conclude that oliguria is common in critically ill patients and results from renal hypoperfusion and ADH excess.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321774 TI - A double-blind assessment of segmental sensory changes with epidural fentanyl versus epidural saline in patients undergoing extracorporeal shock-wave lithotripsy. AB - Segmental changes to pin prick and cold stimuli were tested in a double-blind manner in pain-free patients scheduled for extracorporeal shockwave lithotripsy (ESWL). Fifty patients were randomly allocated to receive either epidural fentanyl (100 micrograms in 10 ml normal saline) or 10 ml epidural normal saline. In a further 25 patients an epidural catheter was inserted but no solution injected. In contrast to this latter group, epidural fentanyl and normal saline both produced segmental sensory changes. There were no significant differences between fentanyl and normal saline groups in the number of patients reporting sensory changes to pin prick, rate of onset of these changes, or segmental level. For cold stimuli, more patients in the fentanyl group than in the normal saline group reported a change (16 vs. 8; P = 0.02) but the segmental level was similar. The effect of normal saline as a diluent in epidurally administered opioids may be of clinical importance. PMID- 2321775 TI - Comparison of transesophageal echocardiographic and scintigraphic estimates of left ventricular end-diastolic volume index and ejection fraction in patients following coronary artery bypass grafting. AB - Transesophageal echocardiography (TEE) has become a commonly used monitor of left ventricular (LV) function and filling during cardiac surgery. Its use is based on the assumption that changes in LV short-axis ID reflect changes in LV volume. To study the ability of TEE to estimate LV volume and ejection immediately following CABG, 10 patients were studied using blood pool scintigraphy, TEE, and thermodilution cardiac output (CO). A single TEE short-axis cross-sectional image of the LV at the midpapillary muscle level was used for area analysis. Between 1 and 5 h postoperatively, simultaneous data sets (scintigraphy, TEE, and CO) were obtained three to five times in each patient. End-diastolic (EDa) and end systolic (ESa) areas were measured by light pen. Ejection fraction area (EFa) was calculated (EFa = (EDa - ESa)/EDa). When EFa was compared with EF by scintigraphy, correlation was good (r = 0.82 SEE = 0.07). EDa was taken as an indicator of LV volume and compared with LVEDVI which was derived from EF by scintigraphy and CO. Correlation between EDa and LVEDVI was fair (r = 0.74 SEE = 3.75). The authors conclude that immediately following CABG, a single cross sectional TEE image provides a reasonable estimate of EF but not LVEDVI. PMID- 2321776 TI - Continuous epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor. AB - A randomized, double-blind, placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor in nulliparous women. When the cervix was fully dilated, coded study solution was substituted for the known bupivacaine-fentanyl solution. The study solution for 29 patients was 0.0625% bupivacaine-0.0002% fentanyl; 34 patients received saline placebo. The two groups had similar pain scores during the first stage of labor. During the second stage, pain scores were significantly higher in the saline placebo group at each 30-min interval between 60 and 150 min after the diagnosis of full cervical dilation. Similarly, there was a significant difference between the two groups in global assessment of analgesia quality during the second stage, but the difference occurred in those patients with a second-stage duration of greater than or equal to 60 min. Among the women who delivered vaginally, eleven of 28 (39%) women in the bupivacaine-fentanyl group, versus five of 34 (15%) in the saline-placebo group, had surgical perineal anesthesia for vaginal delivery (P less than .05). Six of 28 (21%) women in the bupivacaine-fentanyl group, and five of 34 (15%) in the saline-placebo group, underwent instrumental vaginal delivery (P = NS). The median duration of the second stage of labor was 53 min (range = 5-283) in the bupivacaine-fentanyl group, and 63 min (range = 16-181) in the saline-placebo group (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321777 TI - Safety of general anesthesia in patients previously tested negative for malignant hyperthermia susceptibility. AB - Anesthetic management and outcome were examined in patients with negative in vitro contracture tests for malignant hyperthermia (MH). Contracture testing was performed in a standardized fashion using 3% halothane alone and incremental doses of caffeine alone. Medical records were examined for 54 anesthetic exposures in 42 MH(-) patients who had received anesthesia since their MH testing. Sixteen patients received anesthesia with known MH triggering agents on 23 occasions, all without incident. In six MH(-) patients with previous masseter muscle rigidity, no adverse reactions occurred in response to volatile anesthetic agents. Succinylcholine was avoided in these patients. Eleven MH(-) patients were managed as if MH-susceptible, although it was known that these patients had tested MH(-). Two of these patients also receive prophylactic iv dantrolene. These results suggest that "triggering" anesthetic agents may be safely administered to patients who test MH(-) by in vitro contracture testing. However, until the anesthetic experience of larger numbers of MH(-) patients is known, these results should be interpreted cautiously. PMID- 2321778 TI - Labor analgesia with epidural bupivacaine plus fentanyl: enhancement with epinephrine and inhibition with 2-chloroprocaine. AB - Epidural injection of drug combinations may decrease toxicity by decreasing the dose of each component, but may also result in detrimental drug interactions. In this study interactions among bupivaciane, fentanyl, epinephrine, 2 chloroprocaine, and lidocaine for epidural analgesia during labor were examined. In part 1 of the study, healthy parturients received in a random manner either 10 ml of 0.25% bupivacaine with 5 micrograms/ml fentanyl (n = 50), or 10 ml of this combination with 3.33 micrograms/ml freshly added epinephrine (n = 50). Epinephrine prolonged the median duration of pain relief (180 vs. 138 min, P less than 0.05) without affecting duration of first or second stages of labor, or neonatal Apgar scores. Blood pressure decreased slightly more in those receiving epinephrine, although the incidence of hypotension requiring treatment did not differ between groups. Part 2 of the study evaluated the possibility that local anesthetic used for confirming catheter tip location may interfere with the analgesic action of this bupivacaine-fentanyl-epinephrine (BFE) combination. In 50 additional parturients, a test dose of either 2-chloroprocaine (n = 25) or lidocaine (n = 25) was injected through the epidural catheter and was followed by injection of the BFE mixture. The lidocaine test dose group had a greater duration of analgesia than the 2-chloroprocaine test dose group (median duration of 164 vs. 91 min, P less than 0.05). The authors conclude that the addition of epinephrine 3.33 micrograms/ml significantly increases the duration of analgesia obtained from 0.25% bupivacaine with 5 micrograms/ml fentanyl. However, prior injection of 2-chloroprocaine, but not lidocaine, significantly decreases the duration of analgesia achieved with this BFE mixture. PMID- 2321779 TI - Stimulation with submaximal current for train-of-four monitoring. AB - The present study evaluated responses to train-of-four (TOF) stimulation at a range of stimulating currents. Traditionally TOF has been applied with a supramaximal stimulus but this may be quite uncomfortable for the awake patient. In the first part of this study, 12 healthy volunteers quantified (by 10-cm visual analog scale) the discomfort associated with TOF stimulation at 20, 30, and 50 mA. The median VAS scores were 2, 3, and 6, respectively (P less than 0.05 for differences between each group). In the second part, single twitch and TOF responses were compared at 20, 30, and 50 mA in 64 postoperative and in 19 intraoperative patients who had ratios of the fourth to the first twitch (T4/T1) ranging from 0.15-1.03. In all patients, neuromuscular responses to nerve stimulation were recorded by a mechanogram, and the T4/T1 ratios were calculated. Although single twitch heights increased significantly as amperage was increased, there was no statistical difference in the T4/T1 ratios at the three different currents. The mean +/- SD T4/T1 ratios at 20, 30, and 50 mA were 0.795 +/- 0.247, 0.798 +/- 0.237, and 0.802 +/- 0.233, respectively (P = ns). It is concluded that TOF monitoring using a submaximal stimulus is more comfortable for the awake patient who is suspected of residual weakness, and that T4/T1 testing can be reliably accomplished intraoperatively as well as postoperatively using submaximal stimuli. PMID- 2321780 TI - Comparison of 0.5% ropivacaine and 0.5% bupivacaine for epidural anesthesia in patients undergoing lower-extremity surgery. AB - Ropivacaine is an amide local anesthetic structurally related to, but appearing less cardiotoxic, than bupivacaine. The authors' investigation was designed in a randomized, double-blind fashion to compare the clinical effectiveness of ropivacaine and bupivacaine in patients undergoing lower-extremity surgery. Forty five patients were randomized to receive 20 ml of 0.5% ropivacaine or bupivacaine. Intermittent sensory (pinprick) and motor (Bromage score) measurements were made while the block was in effect, and changes in heart rate, blood pressure and amounts of additional analgesics, sedatives and other medications were also recorded. Presence of tourniquet pain and the quality of anesthesia were also assessed. One patient was excluded from analysis; thus, 22 patients each received ropivacaine or bupivacaine. No differences were found in patient or perioperative characteristics between the groups. The quality and extent of sensory and motor blockade between groups were comparable, although bupivacaine was slightly longer acting. Cardiovascular changes, incidence of tourniquet pain, and the amounts of supplemental medications necessary were also similar between groups. The authors found 0.5% ropivacaine and bupivacaine to be clinically similar in both sensory- and motor-blocking characteristics, with the exception that bupivacaine produced a blockade of slightly longer duration. Because ropivacaine is reported to be less cardiotoxic than bupivacaine in animal studies, the similarity of clinical epidural anesthesia may make ropivacaine the preferred agent. PMID- 2321781 TI - A comparison between bupivacaine instillation versus ilioinguinal/iliohypogastric nerve block for postoperative analgesia following inguinal herniorrhaphy in children. AB - This study compared the postoperative pain relief provided by simple instillation of bupivacaine into a hernia wound with that provided by ilioinguinal/iliohypogastric (IG/IH) nerve block. Sixty children undergoing inguinal hernia repair under general anesthesia were randomized to receive 0.25 ml/kg of 0.25% bupivacaine for either IG/IH nerve block or up to 0.5 ml/kg of the same solution for instillation nerve blocks. In the postanesthesia care unit (PACU), a trained blinded observer evaluated the patient's level of postoperative pain using a standardized 10-point objective pain scale. Fentanyl 1-2 micrograms/kg was administered intravenously to any child scoring 6 or more points on the pain scale. The difference in pain scores among the two groups were compared. The two groups were not significantly different in age, duration of surgery, or anesthesia. There was no significant difference between patients who received the two treatment modalities in their pain scores, analgesic requirements in the PACU, recovery times, and discharge times. These results demonstrate that the simple instillation of local anesthetics into a wound provides postoperative pain relief following hernia repair, which is as effective as that provided by intraoperative IG/IH nerve block. PMID- 2321782 TI - Understanding pharmacokinetics and pharmacodynamics through computer stimulation: I. The comparative clinical profiles of fentanyl and alfentanil. AB - The authors have used computer simulation to examine the time course of the plasma concentration, estimated effect site concentration, and the intensity of the central nervous system (CNS) effect of fentanyl and alfentanil. The simulations were performed over a range of clinically equivalent doses. Simulations of the changes in the processed electroencephalogram (EEG) was used as a reflection of drug induced CNS effect. The simulations reveal that the rate of equilibration between effect site and plasma concentrations can explain differences in the clinical time course of drug effect between these opioids. The onset of fentanyl EEG drug effect is delayed relative to alfentanil and the duration of action is longer. Pharmacokinetic differences do not explain the disparity seen in the time courses of EEG drug effect. Alfentanil and fentanyl have similar plasma disposition curves during the first 90 min. The concentrations at the effect site are, however, quite different. The simulations illustrate how fentanyl's slow blood:brain equilibration can dampen the rate of rise and fall of effect site concentrations. As a mechanism for terminating effect, redistribution of opioid from effect site to other body regions is less relevant for fentanyl compared with that for alfentanil. The evanescent clinical effects of alfentanil can be explained by the rapid blood:brain equilibration. Computer simulation is a useful tool for revealing relevant determinants of the complex relationship between dose and the time course of effect. PMID- 2321783 TI - Effects of sevoflurane and isoflurane on cardiac and coronary dynamics in chronically instrumented dogs. AB - To assess the hemodynamic properties of the new inhalational anesthetic sevoflurane, 22 dogs were chronically instrumented for measurement of heart rate, aortic, left ventricular and left atrial pressures, cardiac output, and coronary blood flow. Dogs were randomly assigned to two groups, receiving either 1.2 and 2 MAC of sevoflurane (n = 11) or isoflurane (n = 11). At 1.2 and 2 MAC, sevoflurane produced an increase in heart rate (+60 +/- 12% and +54 +/- 9%, respectively), dose-dependent aortic hypotension (-22 +/- 4% and -38 +/- 4%, respectively), systemic vasodilation (-22 +/- 5% and -19 +/- 5%, respectively), dose-dependent decrease in stroke volume (-31 +/- 6% and -48 +/- 4%, respectively), and left ventricular dP/dt (-40 +/- 4% and -61 +/- 10%, respectively). Cardiac output decreased only at 2 MAC (-17 +/- 6%). Finally, coronary blood flow increased at 1.2 MAC of sevoflurane (+29 +/- 8%). Except for heart rate, sevoflurane and isoflurane produced similar effects. At 1.2 MAC, sevoflurane produced a greater increase in heart rate than isoflurane (+60 +/- 12% vs. +33 +/- 9%). The authors conclude that, except for heart rate, the effects of sevoflurane on cardiac function and coronary blood flow are almost identical to those induced by isoflurane in the chronically instrumented dog. PMID- 2321784 TI - Cardiopulmonary resuscitation with interposed abdominal compression after asphyxial or fibrillatory cardiac arrest in pigs. AB - The purpose of this study was to compare the efficacy of standard cardiopulmonary resuscitation and cardiopulmonary resuscitation with interposed abdominal compression for restoration of spontaneous circulation in an asphyxial and fibrillatory arrest model. Twenty-eight pigs weighing 19-27 kg were randomly allocated to two arrest groups. Each of these two groups was then subdivided into a treatment group and a control group resulting in four groups of seven pigs each. In the control groups standard cardiopulmonary resuscitation was performed with a pneumatically driven chest compressor at a rate of 80 beats per min. The animals' lungs were ventilated at a respiratory rate of 20 breaths per min independently of chest compression. In the treatment group, in addition to standard cardiopulmonary resuscitation, manual interposed abdominal compression was applied at the midabdomen in the second half of the relaxation phase using a blood pressure cuff to measure and standardize the compressions. Following asphyxial cardiac arrest of 3 min, none of the seven animals could be resuscitated with standard cardiopulmonary resuscitation, whereas all seven animals could be resuscitated with interposed abdominal compression and standard cardiopulmonary resuscitation after 240 +/- 84 s. Following fibrillatory cardiac arrest of 4 min, none of the seven animals that received standard cardiopulmonary resuscitation and countershocks could be resuscitated. In the group that received standard cardiopulmonary resuscitation and interposed abdominal compression spontaneous circulation was achieved in all animals in 244 +/- 117 s. End diastolic arteriovenous pressure difference, which correlates with coronary blood flow, was significantly higher with interposed abdominal compression during resuscitation from both forms of cardiac arrest. The results of our study indicate that cardiopulmonary resuscitation with interposed abdominal compression in the second half of the relaxation phase improves diastolic arteriovenous pressure difference and resuscitation success in comparison with that following standard cardiopulmonary resuscitation. The use of interposed abdominal compression during basic cardiac life support should be investigated further in patients. PMID- 2321785 TI - Low-dose halothane anesthesia does not affect the hemodynamic estimation of myocardial oxygen consumption in dogs. AB - The accuracy of the product of systolic blood pressure and heart rate as a correlate of myocardial oxygen consumption has been questioned in anesthetized patients, suggesting that anesthesia alters the relationship between myocardial oxygen consumption and the hemodynamics. This relationship was reexamined in the awake state and during 0.95% end-tidal halothane anesthesia in seven chronically instrumented dogs. Measurements of myocardial oxygen consumption were compared with two indices, the systolic pressure rate product and the pressure work index. The latter is a weighted combination of the systolic pressure rate product and external cardiac work. A wide range in myocardial oxygen consumption (3.0-38.2 ml O2.min-1.100g-1) and hemodynamic states (range in pressure rate 4,100-40,700 mmHg/min and range in pressure work 3.7-37.0 ml O2.min-1.100g-1) was achieved with infusions of norepinephrine, nitroglycerin, neosynephrine, nitroprusside, and isoproterenol. Both the pressure rate product and the pressure work index correlated closely with myocardial oxygen consumption not only when the animals were awake but also during anesthesia. For each animal best-fit regression analysis for the awake and the anesthetized data did not reveal any significant change in the slope or y-intercept. Pooled data analysis that only permitted a change in slope with the addition of anesthesia (intercept unchanged) revealed a 17% decrease (P less than 0.05 on t test) in the slope constant when the pressure rate product was applied and no change in slope when the pressure work index was used to estimate myocardial oxygen consumption. It was concluded that myocardial oxygen consumption can be estimated during 0.95% halothane anesthesia by either index but that the pressure work index performs better than the systolic pressure rate product. PMID- 2321786 TI - Direct effect of halothane and isoflurane on the function of the sarcoplasmic reticulum in intact rabbit atria. AB - The negative inotropic effect of halothane and isoflurane on potentiated-state contractions of isolated rabbit atria in a normal Ca2+ (2.5 mM) medium was compared with the force depression in low Ca2+ media without an anesthetic. When this comparison was made in the presence of 1 microM ryanodine so that the force of contraction was dependent only upon transsarcolemmal Ca2+ influx with no Ca2+ contribution from the sarcoplasmic reticulum (SR), the force of contraction was depressed equally by 0.6% halothane in a normal Ca2+ medium and by a 1.5 mM Ca2+ medium without the anesthetic. Similarly, 1.0% halothane or 1.5% isoflurane and a 1.0 mM Ca2+ medium were equally depressant as were 2.4% isoflurane and a 0.5 mM Ca2+ medium. In the absence of ryanodine, where the atrial contractile activity is largely dependent on Ca2+ released from the SR, 0.6% halothane in the normal Ca2+ medium depressed contractile force by 32%, whereas the force was depressed by only 16% in the 1.5 mM Ca2+ medium without the anesthetic. Similar results were obtained when the effects of 1.0% halothane and of 1.0 mM Ca2+ were compared. In contrast, the force of contraction measured in the absence of ryanodine was not at all inhibited by 1.5% isoflurane and minimally (11%) inhibited by 2.4% isoflurane. Consequently, the force depression by isoflurane was less than that found in the low Ca2+ media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321787 TI - Synergistic interaction of morphine and halothane in the guinea pig ileum: effects of pertussis toxin. AB - The effects of pertussis toxin on the actions of morphine and halothane in the guinea pig ileum are described. Both morphine and halothane produce a dose related inhibition of electrically induced muscle contraction. The IC50 of morphine was unchanged by the toxin (2.1 and 2.2 X 10(-7) M in control and toxin pretreated animals). However, the IC50 of halothane was increased from 2.1 to an extrapolated value of 9.1 vol/vol% by pertussis toxin. At high levels of inhibition the interaction between morphine and halothane was synergistic and was converted to additive in the presence of the toxin. These results demonstrate that in the myenteric longitudinal muscle preparation the effects of halothane, but not those of morphine, are mediated by the substrate for pertussis toxin, possibly a Gi membrane protein. The present study provides significant evidence that the effects of halothane on neuronal tissue are dependent upon an interaction with a specific membrane protein. PMID- 2321788 TI - Work and rest cycles in anesthesia practice. AB - A questionnaire inquiring about existing and desirable work and rest patterns appeared in a newsletter mailed to about 22,000 anesthesiologists and anesthesiology residents and 24,000 nurse anesthetists (CRNA). Almost 3,000 anonymous replies were received and analyzed. Respondents reported mean work weeks of 47.5 h (CRNA) to 69.8 h (residents), longest continuous period of administering anesthesia without a break of 6.6 h (CRNA) to 7.7 h (residents), and longest period of administering anesthesia with or without breaks of 14.1 h (CRNA) to 20 h (resident). However, the respondents considered it safe to administer anesthesia without a break for 4.2 (CRNA) to 5.2 h (anesthesiologists) and with break for 12.8 h (CRNA) to 15 h (residents). A substantial number of respondents believed that they work at least occasionally beyond their perceived self-limitations. The majority of respondents recalled having made errors in the administration of anesthesia that they attributed to fatigue. These results may not be representative of work patterns or attitudes among American anesthesia providers because of the small sample size and the resultant potential for bias. Yet, the subject deserves attention and further study because fatigue can affect professional performance, ability to learn, and family life. PMID- 2321789 TI - A new application for superior laryngeal nerve block: transesophageal echocardiography. PMID- 2321790 TI - Hypoplastic left heart syndrome: anesthesia for elective noncardiac surgery. PMID- 2321791 TI - Cholecystectomy in a patient with paroxysmal nocturnal hemoglobinuria: anesthetic implications and management in the perioperative period. PMID- 2321792 TI - Transient anterior spinal cord syndrome with continuous postoperative epidural analgesia. PMID- 2321793 TI - What constitutes adequate anesthesia in animals? In neonates? PMID- 2321794 TI - Cardiovascular responses to noxious stimuli in experimental animals: "pressor or depressor"? PMID- 2321795 TI - A pain in the neck--and shoulder. PMID- 2321796 TI - Cardiac arrest in a day surgery patient. PMID- 2321797 TI - Cardiac effects of anabolic steroids. PMID- 2321798 TI - Preventing delivery of hypoxic gas mixtures. PMID- 2321799 TI - Ventricular tachycardia associated with injection of prostaglandin F2 alpha into the uterine cervix during anesthesia. PMID- 2321800 TI - [Heparin-induced hemorrhage in the treatment of venous thromboembolism]. AB - Retrospective study about the frequency of hemorrhagic complications (258 patients) in the treatment of venous thrombosis and/o pulmonary embolism, with heparin. Heparin was intermittently administered by endovenous way and controlled during the ten first days. Mostly of the big hemorrhages happened between the seventh and the tenth day, in digestive and urinary system mainly. PMID- 2321801 TI - [Surgical treatment of tumors of the carotid body with reconstruction of the internal carotid artery]. AB - The experience about treatment in infiltrating tumors of Carotid Corpus, III Degree (Shamblin), is presented. Different methods of carotid reconstruction, and biologic and evolutive characteristics are emphasized, discussing preoperatory study and surgical technics. PMID- 2321802 TI - [Chromatic micropuncture in the treatment of telangiectasis]. AB - An original treatment of Telangiectasias based in microsurgery, with venous destruction and collagen-pigment implant (procedure called "Chromatic micropuncture"), is exposed. PMID- 2321803 TI - [Biophysical study of resistance in arterial anastomoses. Experimental results]. AB - Experimental study about suture materials of mean velocity absorption, in order to demonstrate their capacity to obtain a correct and sure arterial cicatrization by means of their tensile force, even though they disappear afterwards by absorption. 32 arterial anastomosis were carry out, and all of them resisted 300 mmHg of pressure, without to be broken. PMID- 2321805 TI - Spacers in childhood asthma--is there one for all occasions? PMID- 2321804 TI - [Malleable spatulas in surgery of primary and secondary varices of the legs]. AB - A variant of Cigorraga's method, in order to eliminate communicant veins in lower limbs varix, is exposed. To localize and cut these communicants, two spatulas, one with rounded end and the other with semilunar and cutting end, are employed. PMID- 2321806 TI - Episodes of sudden weight gain, arthralgia, and hematuria in a middle aged woman. PMID- 2321807 TI - Adrenal cortical function after long-term beclomethasone aerosol therapy in early childhood. AB - Ten asthmatic children were studied by tetracosactrin stimulation tests after receiving beclomethasone dipropionate aerosol (BDA) for periods of up to 12 months. Clinical improvement occurred in all children while receiving BDA. No change in adrenal function could be demonstrated by comparing the tetracosactrin stimulation tests before and after treatment with BDA. PMID- 2321809 TI - Purification and characterization of an allergen of mustard seed. AB - A protein allergen has been isolated from mustard seed extracts by gel filtration. In RAST-inhibition experiments the allergen inhibited more than 60% of the binding of mustard-specific IgE from a pool of seven patients' sera. The allergenic activity was also demonstrated by histamine release from whole blood from two sensitive patients. The allergen had an isoelectric point close to 10.5 and an apparent molecular weight of 14,000. It was stable in alkaline and acid solutions and showed resistance to heating and to degradation by proteolytic enzymes. PMID- 2321808 TI - Preliminary investigation on humoral and cellular immune responses to selected food proteins in patients with Crohn's disease. AB - Crohn's disease is a chronic inflammatory disorder for which an immunologic etiology has been proposed. Food hypersensitivity may contribute to part of the pathogenesis of this disorder. In preliminary studies, we evaluated 11 Crohn's patients by history, skin testing (ST), total and specific(s) IgE and sIgE/sIgG4 levels to five food proteins [egg (E), milk (M), wheat (W), soy (S), and corn (C)] using a sensitive enzyme monoclonal antibody assay. Skin testing was also performed using grass and mold allergens. Lymphocyte concanavalin (Con A) mitogenic and antigenic responses to food proteins were also determined by tritiated thymidine incorporation. Mean sIgG4 values for four food proteins are listed below: (Table: see text). No patient reacted with elevated sIgE or sIgG4 to corn. All patients had low to negative sIgE levels to all foods and only three had increased total IgE. Three of eight were history and ST positive to M, E, and W. Six of eight had at least one positive ST to M, E, W, and S. All patients had negative sIgG4 to tested inhalants and two had elevated sIgE to grass pollen. Although mean lymphocyte Con A mitogenesis was significantly decreased in eight patients compared with controls (P less than .05), an increased food stimulatory response to milk protein was observed (P less than .05). Perhaps, decreased sIgE and cell-mediated mitogenic responsiveness may lead to an enhanced humoral IgG response. The increased sIgG4 humoral response to egg protein and cellular sensitivity to milk protein may indicate mucosal antigenic stimulation or leakage in patients with Crohn's disease in spite of negative sIgE levels. PMID- 2321811 TI - Kerosene-induced asthma. AB - Clinical evaluation of 286 asthmatic women showed 15.5% of those who improved clinically had contact with kerosene, while 43.9% of those who failed to improve used kerosene as fuel for cooking. In 16 women the onset of asthma occurred soon after they began to use kerosene. Kerosene can cause and aggravate asthma. PMID- 2321812 TI - Physician reported patient response to immunotherapy: a retrospective study of factors affecting the response. AB - This study assessed physician evaluation of immunotherapy derived from questionnaires completed at specified intervals during the course of each program in 901 randomly selected patients in the Allergy Clinic, Kingston General Hospital, (1975 to 1985). The objective was to determine safety and efficacy and factors contributing to these from this information. Approximately ninety-six percent of completed questionnaires and 97.5% of patients reported symptomatic improvement. The requirement for supplemental medication was reported in 21.6% of questionnaires and by 35.6% of patients. This requirement was greater in females, in patients with asthma, and in patients with greater numbers of antigens administered. Single antigen programs provided the best response. Systemic reactions were reported in 6.7% of patients treated. In 1% of patients these reactions were severe and required adrenalin for management. Severe reactions occurred when higher concentrations of antigens were injected and frequently developed without warning of prior milder episodes. It was concluded that immunotherapy programs are safe and effective given in appropriate circumstances and with proper safeguards. A monitoring system, however, would provide valuable information on patient progress and collectively may indicate trends in response. PMID- 2321810 TI - Dermatophagoides and storage mites: statistical analysis of RAST results. AB - R.I.A. dosages of specific IgE antibodies to Dermatophagoides pteronyssinus, Dermatophagoides farinae (house dust mites), Acarus siro, Lepidoglyphus destructor, and Tyrophagus putrescentiae (storage mites) in 467 unselected patients were statistically analyzed. A significant noncorrelation between specific IgE antibodies to storage mites and those to house dust mites has been found, suggesting that storage mites have their own allergenic specificity. PMID- 2321814 TI - Training perception of acute airflow obstruction. AB - Ten asthmatics selected for their tendency to experience frequent acute exacerbations were instructed in peak flow measurement. Each subject then recorded estimated peak flow (EPF) and measured peak flow (PF) at home twice daily. Data for up to 56 consecutive observations (4 weeks) per subject were analyzed. The correlation coefficient between EPF and PF following PF drops of 15% was .993 overall and was not significantly different following PF drops even greater than 25%. The absolute and proportional differences between PF and EPF were also not significantly affected by the magnitude of PF drop but decreased over time indicating improved accuracy of estimates with practice. Asthmatics can be trained to estimate accurately acute drops in airflow. Such ability has not been demonstrated in prior studies which utilized verbal symptom reports as indicators of subjective perception of airflow. Accurate perception would be a useful aid in achieving early recognition of acute exacerbations and in improving medication compliance. It is an adjunct to regular peak flow measurement, not a substitute for it. PMID- 2321813 TI - Comparison of in vivo and in vitro tests in the diagnosis of imported fire ant sting allergy. AB - The specificities and sensitivities of skin test reactivity to imported fire ant (IFA) whole body extract (WBE) and IFA venom were compared with IFA WBE RAST and IFA venom RAST in the diagnosis of IFA allergy. Study groups consisted of 18 IFA allergic patients and 21 control subjects with no history of allergy to insect stings. All IFA allergic patients had positive skin tests to both IFA WBE and IFA venom. Six of 21 (29%) control subjects also had positive skin tests to both IFA WBE and IFA venom. A commercial IFA WBE RAST was positive in 10 of 18 (56%) IFA allergic patients and 2 of 21 (10%) control subjects. Imported fire ant aqueous venom RAST was positive in 11 of 11 (100%) IFA-allergic patients and three of ten (30%) control subjects. Vespa IFA venom RAST was positive in 16 of 18 (89%) IFA allergic patients and 5 of 21 (24%) controls. The sensitivities and specificities of IFA WBE skin testing, IFA venom skin testing, and IFA venom RAST did not differ significantly. Imported fire ant WBE RAST was less sensitive than the other diagnostic methods. PMID- 2321815 TI - Exercise-induced anaphylaxis in a 4-year-old boy. PMID- 2321816 TI - Measurement of bronchial hyperreactivity in infants and preschool children using a new method. AB - We report a new method for examination of bronchial reactivity by measuring transcutaneous oxygen pressure (tcPO2) during the inhalation of histamine in stepwise incremental concentrations. The correlation between changes in tcPO2 and those in PEFR or FEV1 was high (P less than .001). When the fall in PEFR or FEV1 was more than 20% compared with baseline, the fall in tcPO2 was more than 10%. We also measured the dose of radiolabeled aerosol (99mTc-DTPA) inhaled into the lung using a scintillation camera. When aerosol is inhaled during tidal breathing, there are adequate correlations between the dose of aerosol in the lung and both the age and height of the patients (P less than .001). When aerosol was inhaled during crying, little deposit within the lung was shown. When the inhalation challenge test was done during a sleeping period for children aged under 2 years, the loading dose of aerosol in the lung was sufficient. The geometrical means of respiratory threshold of histamine (RT-Hist) among 106 asthmatic and 11 control children, aged 2 to 6 years, were 1182 and 4414 micrograms/mL, respectively. The means of RT-Hist in 17 children with bronchial asthma, nine with atopic dermatitis, five with respiratory disease, and nine controls, aged under 2 years, were 1152, 964, 544, and 3402 micrograms/mL, respectively. PMID- 2321817 TI - Bronchoalveolar lavage for pneumocystis pneumonia in HIV-infected children. AB - Bronchoalveolar lavage (BAL) by flexible fiberoptic bronchoscopy is useful in the diagnosis of Pneumocystis carinii pneumonia (PCP) in adults with acquired immunodeficiency syndrome. To evaluate the safety and efficacy of this procedure in children with human immunodeficiency virus in whom PCP was considered, we reviewed the records of 15 consecutive procedures performed on eight patients by a pediatric pulmonologist during a 19-month period. Pneumocystis carinii pneumonia was identified after five of 15 BAL procedures. Other pathogens or multiple pathogens were found in some cases. A specific infectious diagnosis was obtained in ten of 15 procedures. No patient required subsequent open lung biopsy. Follow-up for a minimum of 6 weeks and response to therapy did not suggest PCP in any case where BAL failed to establish its diagnosis. No major complication was attributed to BAL. We conclude that BAL is safe and effective in the diagnosis of PCP in children with HIV infection. Guidelines are suggested to optimize its safety and utility. PMID- 2321818 TI - Fiberoptic intubation in the emergency department. AB - Fiberoptic-aided endotracheal intubation has been shown to be effective in difficult intubation secondary to anatomic abnormalities and traumatic conditions. A retrospective review of emergency airway management in an emergency department during a 30-month period found 35 patients who underwent fiberoptic aided endotracheal intubation; 31 were treated for medical conditions, and four were trauma patients. Indications in the medical group included failed nasotracheal intubation (ten), anatomic abnormalities (six), and the initial airway maneuver attempted (15). Indications in the trauma group with suspected cervical-spine injury included failed nasotracheal intubation (one) and initial airway maneuver attempted (three). In the medical subgroup, 25 of 31 patients were intubated successfully fiberoptically. All four trauma patients were intubated successfully, and all attempts were done nasally. The limitations of the technique were varied. Twenty of the 25 successful intubations had times recorded for completion (mean time, 1.8 +/- 1.4 minutes [SD]). Four of the six failed attempts had recorded times of 7.8 +/- 1.4 minutes. The mean time of the four trauma cases was 3 +/- 2.2 minutes. The presence of secretions, blood, or vomitus was the cause in five of the six failed intubations. The sixth patient kept swallowing the distal end of the scope. Fiscal restraints may also limit its use. At our institution, the financial commitment has been approximately +17,000 during the past nine years. Repair or replacement of broken equipment appears to be necessary every two or three years. Immediate airway control is often difficult with fiberoptic-aided endotracheal intubation and should be used only in selected patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321819 TI - Use of autopsy results in the emergency department quality assurance plan. AB - Traditionally, the autopsy is viewed as the ultimate quality assurance indicator in clinical medicine, yet very few clinical departments actually incorporate autopsy results in their formal quality assurance plans. Consequently, to investigate how autopsy results can be included on our emergency department plan, the clinical and autopsy diagnoses of 244 patients were reviewed retrospectively and compared to identify conditions that were unapparent or misdiagnosed at the time of death. The study period was from January 1984 through June 1988. The average yearly ED census was 33,266. Differences between clinical and autopsy diagnoses were categorized as class 1, 2, 3, or 4 findings. Major unexpected findings (classes 1 and 2) were found in ten patients (4%); the most common missed diagnoses were aortic dissection 3 (1.2%) and pulmonary embolus 2 (0.8%). Minor unexpected findings (classes 3 and 4) were discovered in 14 patients (5.8%). The results clearly identify unexpected findings and point to the need for more aggressive evaluations of certain conditions. Systematic review of autopsy data as presented has led to meaningful changes and delivery of care to emergency patients. Autopsies are a vital source of outcome-based information that should be part of every ED's quality assurance and risk management plan. PMID- 2321820 TI - Compliance with a standard for the emergency department management of epileptics who present after an uncomplicated convulsion. AB - We conducted a retrospective chart review to determine whether the treatment of uncomplicated convulsions in emergency department patients with a history of epilepsy complied with a clinical standard and whether the degree of compliance with the standard was related to the treating physician's specialty or postgraduate year of training. The standard specified items to be included in the medical record and appropriate diagnostic tests. A medical record score was defined by the presence of seven essential and seven desirable items obtained from the history and the physical examination. Only anticonvulsant levels and a serum glucose, when not ordered as part of a chemistry profile, were considered appropriate for all patients when drawn. A computed tomography head scan was deemed appropriate for patients whose neurologic status deteriorated or failed to return to baseline within one hour or who had a recent history of significant head trauma. The appropriateness of all other tests was evaluated by review of the medical record. One hundred consecutive ED visits by adult epileptics for an uncomplicated convulsion were considered. Patients ranged in age from 18 to 88 years (median, 28 years). Medical record scores ranged from 7 to 82 (median, 43). ED time ranged from eight to 539 minutes (median, 174.5 minutes). Ancillary services charges ranged from +0 to +1,774 (median, +181.50). Only 27.4% of these charges were for tests deemed appropriate. There was a significant relationship between the ED time and ancillary services charges (Spearman correlation = .5152, P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321821 TI - Utility of laboratory studies in the emergency department patient with a new onset seizure. AB - Extensive laboratory testing is often performed in the emergency department evaluation of the new-onset seizure patient. To determine the utility of such testing, a prospective study of patients with a new-onset seizure presenting to the ED of an inner-city, university-affiliated teaching hospital was done. One hundred thirty-six patients were entered into the study between October 1984 and January 1988. All patients had uniform data collection performed. Pertinent historical information and physical examination findings were recorded on a standardized form before laboratory abnormality was a sole or contributory cause of the seizure disorder. These included four patients with hypoglycemia, four with hyperglycemia, two with hypocalcemia, and one with hypomagnesemia. Only two cases (hypoglycemia) were not suspected on the basis of findings on the history or physical examination. In ED patients, the incidence of a new-onset seizure due to a correctable metabolic disturbance is low. We conclude that, with the exception of the serum glucose, the extensive ED laboratory workup often done for the evaluation of a new-onset seizure is unnecessary. Further test ordering should be directed by the medical history and physical examination. PMID- 2321822 TI - Nonsteroidal anti-inflammatory drugs and coma: a case report of fenoprofen overdose. AB - We present the case of a 17-year-old girl who ingested 24 to 36 g fenoprofen as a suicidal gesture. She presented with coma, hypotension, metabolic acidosis, and respiratory depression within four hours of ingestion. The most common adverse effects of the nonsteroidal anti-inflammatory drugs occur in both therapeutic and toxic doses and include gastrointestinal upset, blood dyscrasias, and analgesic nephropathy. The propionic acid derivatives of nonsteroidal anti-inflammatory drugs, including fenoprofen and ibuprofen, are rarely associated with severe toxic effects. This is the first report of pure fenoprofen overdose presenting as coma and metabolic acidosis. PMID- 2321823 TI - Arterial access in the pediatric emergency department. AB - Arterial catheters are used frequently to monitor critically ill children in ICUs, but their role in the emergency department has not been described. The medical records of all patients admitted to the ICU from the ED of a children's hospital during a 30-month period were reviewed retrospectively. Forty-one patients were identified as having arterial catheters placed in the ED. Catheterization was performed for serial blood gas determinations (59%) or continuous blood pressure monitoring (41%). The radial artery was catheterized in 73% of the 41 patients, and a 22-gauge catheter was used in 78% of the patients. The original catheter was discontinued before the end of medical indication in only 24% of cases--17% were discontinued for failure to draw and 7% for vascular changes at the site of the catheter. We conclude that arterial access can be used for children in the ED to monitor blood pressure and that blood gas tensions and complications are few and generally minor. PMID- 2321825 TI - Two children with lethargy and intussusception. AB - The cases of two patients with lethargy as the predominant symptom of intussusception are described. The first patient was admitted to the pediatric ICU with unexplained lethargy. The diagnosis of intussusception was made after he developed right lower quadrant abdominal tenderness and heme-positive stool. The second patient was diagnosed after presenting to the emergency department with intermittent lethargy, right lower quadrant abdominal tenderness, and heme positive stool. The presence of gastrointestinal symptoms or signs in association with lethargy should alert the physician to the possibility of an intussusception. PMID- 2321824 TI - A pediatric survivor of left ventricular rupture after blunt chest trauma. AB - The case of a patient with left ventricular rupture as a result of blunt chest trauma from a motor vehicle accident is presented. This is the first reported case of a pediatric survivor of this rare and usually lethal injury and only the fourth report of a survivor. This condition can be treated if the patient survives long enough to reach a trauma center, if the diagnosis is entertained early, and if the appropriate diagnostic studies are obtained in an expeditious manner. We believe that echocardiography is the diagnostic method of choice for pericardial tamponade, whether it is the result of penetrating or blunt trauma, and that early use of this modality may improve survivability. PMID- 2321826 TI - Emphysematous cystitis: a complication of urinary tract infection occurring predominantly in diabetic women. AB - The case of a patient with emphysematous cystitis who presented with complaints of lower abdominal pain, dysuria, and pneumaturia is presented. The presenting symptoms, differential diagnosis, and radiographic and cystoscopic appearances of emphysematous cystitis, a rare complication of lower urinary tract infection occurring almost exclusively in diabetics, are reviewed. Treatment consists of urinary drainage, prompt initiation of antibiotic therapy, and strict glucose control. The prognosis usually is excellent. PMID- 2321827 TI - Serous culdocentesis in ectopic pregnancy: a report of two cases caused by coexistent corpus luteum cysts. AB - Two cases of women with large-volume serous culdocentesis results are presented. Both patients ultimately had ectopic pregnancies diagnosed surgically, and aspiration into coexistent corpus luteum cysts caused the "false-negative" culdocentesis results. The accuracy of culdocentesis and its continued role in the workup of the patient with possible ectopic pregnancy is reviewed. Because the corpus luteum is a cystic structure present in all pregnancies during the first seven weeks, cyst aspiration is always a possibility and should be suspected when large amounts of serous fluid are obtained by culdocentesis. Such results should be considered nondiagnostic and do not exclude a coexistent ectopic pregnancy. PMID- 2321828 TI - Stress fracture of the first rib from serratus anterior tension: an unusual mechanism of injury. AB - Fracture of the first rib usually results from high-impact, direct trauma. Stress fractures are less common and are associated with minimal morbidity. The case of a patient with a stress fracture resulting from the use of an exercise machine is reported. Previous reports have attributed stress and fatigue fractures of the first rib to the forces exerted by the scalene muscles. A new pathophysiologic mechanism involving the serratus anterior muscle is introduced and is supported by T2 relaxation times from magnetic resonance imaging. Stress and fatigue fractures of the first rib have minimal complications. An aggressive diagnostic evaluation of first rib fractures occurring by this mechanism is not warranted. PMID- 2321830 TI - Methemoglobinemia secondary to aniline exposure. PMID- 2321829 TI - Emergency department management of patients with automatic implantable cardioverter-defibrillators. AB - The case of a patient with idiopathic dilated cardiomyopathy and complex ventricular arrhythmias who underwent placement of an automatic implantable cardioverter-defibrillator (AICD) and experienced inappropriate shocks during atrial fibrillation is presented. On presentation to the emergency department, the patient had experienced approximately ten device discharges over six hours. ECG revealed atrial fibrillation with a rapid, wide complex ventricular response. Initial management consisted of IV verapamil for rate control followed by deactivation of the AICD. The patient was subsequently hospitalized for treatment of atrial fibrillation. Inappropriate device discharges, a frequently reported AICD-associated complication, are discussed. PMID- 2321832 TI - The role of the emergency physician in the care of children. American College of Emergency Physicians. Pediatric Emergency Medicine Committee. PMID- 2321831 TI - 24-hour coverage in academic emergency medicine: ways of dealing with the issue. PMID- 2321833 TI - Epinephrine versus norepinephrine. PMID- 2321834 TI - Dipstick test in the ED. PMID- 2321835 TI - Abstracts of the 20th annual meeting of the Society for Academic Emergency Medicine. Minneapolis, May 21-24. PMID- 2321836 TI - Budget provisions are victory: advanced practice nurses to benefit. PMID- 2321837 TI - Health care cost overrides need. PMID- 2321838 TI - Congress acts on rural health. PMID- 2321839 TI - ANA is advocate for families. PMID- 2321840 TI - Political action = political power. PMID- 2321841 TI - Legislative initiatives guide ANA action. PMID- 2321843 TI - SNA members are political force. PMID- 2321842 TI - RNs can influence federal budget. PMID- 2321844 TI - SNAs face legislative issues. PMID- 2321845 TI - Nurses face increasing liability. PMID- 2321846 TI - Care for yourself--save for retirement. PMID- 2321847 TI - As I see it. Tougher efforts needed in drug war. PMID- 2321848 TI - RNs can prevent, treat addiction. PMID- 2321849 TI - Expansion of CMT role supported. PMID- 2321850 TI - NCNIP unveils national ad campaign. PMID- 2321851 TI - RN supply still below demand. PMID- 2321852 TI - Nurses address international issues. PMID- 2321853 TI - SNAs maintain lead over unions. PMID- 2321854 TI - Involved RNs know workplace structure. PMID- 2321855 TI - RNs strive to improve working conditions. PMID- 2321856 TI - Prenatal care, AIDS are top concerns. PMID- 2321857 TI - SNA bargaining brings big win for staff RNs. PMID- 2321858 TI - ANA intensifies lobbying efforts. PMID- 2321859 TI - ANA protects nurses' interests. PMID- 2321860 TI - Working through SNAs, nurses change workplace. PMID- 2321861 TI - Risk management is team effort. PMID- 2321862 TI - Social Security isn't enough. PMID- 2321863 TI - Shortage brings frustration. PMID- 2321864 TI - As I see it. Shortage is international problem. PMID- 2321866 TI - Image campaign takes off. PMID- 2321865 TI - Workplace representation: continuing commitment, new choices. PMID- 2321867 TI - Nurses' influence projected to grow during nineties. PMID- 2321868 TI - Image campaign meets the public. PMID- 2321869 TI - Task force tackles health policy. PMID- 2321870 TI - Family, medical leave needed now. PMID- 2321871 TI - Statement clarifies assistants' role. PMID- 2321872 TI - Protecting your life-style. PMID- 2321873 TI - Protecting your life-style. Retirement. PMID- 2321874 TI - Protecting your life-style. Group insurance. PMID- 2321875 TI - Protecting your life-style. Claims data base. PMID- 2321876 TI - Protecting your life-style. Liability insurance. PMID- 2321878 TI - States differ on foreign nurses. PMID- 2321877 TI - ANA urges move on health care. PMID- 2321879 TI - It's time for new civil rights act. PMID- 2321880 TI - Protecting your lifestyle. Informed consent may entail risk. PMID- 2321881 TI - Pepper report supports care. PMID- 2321882 TI - Seizing an exceptional moment: the effectiveness initiative. PMID- 2321883 TI - [Expectations and defeat in the treatment of epithelial cancer of the ovary]. AB - One hundred and thirty-nine patients were treated between 1980 and 1988 for epithelial cancer of the ovary: 35 stage I, 30 stage II, 66 stage III and 8 stage IV (according to the IFGO classification). For stage I and II patients, who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy followed by combination chemotherapy, the 5 year survival rate without relapse was 91%. For those classified as stage III, the 5 year survival rate was 36%. When the tumor was completely removed surgically, the 5 year survival rate was 82%, but the disease-free (without relapse) rate was only 47%. When the malignancy could not be completely excised, the 5 year survival rate was only 15%. The only chance these patients had to survive was if chemotherapy effectively controlled the residual mass (verified during an exploratory laparotomy). In our experience, the combination of cisplatin, doxorubicin and cyclophosphamide, in spite of a 78% response rate, only histologically eliminated the residual tumor in 15% of the patients. PMID- 2321884 TI - [Treatment and evolution of algodystrophy of the foot. Retrospective study of 199 cases]. AB - This retrospective review presents the results of treating 199 patients with sympathetic reflex dystrophy of the foot: 141 of traumatic and 58 of non traumatic origin. Calcitonin (177 patients) improved or cured 62.2 p. 100 of these patients and was equally effective for pseudo inflammatory and ischemic (cold) stages of the disease. Among the therapeutic means available, regional sympathetic blockade with guanethidine (49 patients, 163 treatments) provided 80 p. 100 improvement or cure, with twice as many patients in the hot phase as in the cold. All patients were cured: 75 p. 100 in less than a year, 4.6 p. 100 with moderate, non-handicapping sequelae. Normal activities were partially reinstituted 3.5 +/- 2.8 months (post-trauma) or 1.9 +/- 1 months (non-trauma) after treatment. They were completely possible 5 months after the end of treatment in both groups. In the trauma group, 73 patients had work-related accidents: their evolution was the same as that of the other patients in this group. When present, psychological background (35 p. 100 of the cases) only delayed progress in the non-traumatic group (9.9 vs 6.5 months). PMID- 2321885 TI - [Epidemiologic aspects of viral hepatitis at a Parisian university hospital. Apropos of 130 cases]. AB - One hundred and thirty adults with viral hepatitis were hospitalized in the Department of Hepatology-Gastroenterology at the Hospital Salpetriere between October 1984 and October 1986. Eighty had acute hepatitis and 50 suffered from chronic hepatitis. Among the former, 15 had hepatitis A, 40 had hepatitis B and/or delta and 25 had non A-non B hepatitis. The latter group was divided into 32 hepatitis B and/or delta and 18 non A-non B. The results of clinical, biological, serological and histological analyses were comparable to those reported in the literature for hepatitis A and B. Hepatitis non A-non B was more prevalent in males (72%). This predominance seems to be associated with the high number of heart transplant patients (12, 11 of them were men) in our study population. A liver biopsy was performed on 19 out of the 25 acute and on 32 of the chronic non A-non B hepatitis patients. Persistent chronic hepatitis was the most commonly found lesion. Transfusion was implicated in 53.8% of the patients, drug addiction in 18.6% of the cases and intramuscular injection or acupuncture in 5% of them. No risk factor was found in 23.2% of the patients. Seventy-two percent of the acute non A-non B hepatitis cases evolved towards a chronic form. We have attempted to find the factors involved in progression to chronicity. No correlation was found for age or the means of contamination. In contrast, immunodepression was significantly correlated. This study reflects the prevalence of non A-non B hepatitis infection post-transfusion in a hospitalized population including many transplant recipients. PMID- 2321886 TI - [HELLP syndrome: a severe form of pregnancy toxemia]. PMID- 2321887 TI - [Painful and febrile sternal tumefaction in a Martinique patient]. PMID- 2321888 TI - [Non-infectious mitral endocarditis during Still's disease in adults. A case with histologic study of the endocardium]. PMID- 2321889 TI - [Fulminating hepatitis by type 5 adenoviruses during Hodgkin's disease]. PMID- 2321890 TI - [Factitious thyrotoxicosis with periodic paralysis and rhabdomyolysis]. PMID- 2321891 TI - [Auto-immune pathology after placement of a mersilene preperitoneal plate]. PMID- 2321892 TI - [Chronic hemarthrosis, a new etiology of unexplained prolonged fever. Apropos of a case]. PMID- 2321893 TI - [Benign fibrous tumors of the pleura revealed by articular pathology. 2 cases]. PMID- 2321894 TI - [Bone tuberculosis with involvement of the vertebral arch. Apropos of a case]. PMID- 2321895 TI - [Cervicalgia and vertebral artery loop. Value of magnetic resonance imaging. Apropos of a case]. PMID- 2321896 TI - [Radiotherapy of epidemic Kaposi's sarcoma in patients with AIDS. Analysis of 149 cases treated by extended and/or localized cutaneous irradiation]. AB - Between June 1986 and December 1988, 149 patients with AIDS-related Kaposi's sarcoma were treated by cutaneous irradiation in our department. According to Mitsuyasu's staging, 34 patients (23 p. 100) were stage I, 82 (55 p. 100) stage II and 33 (22 p. 100) stage IV; no stage III was reported. Fifty eight patients (39 p. 100) had previously presented with one or several opportunistic infections. Ninety four patients (63 p. 100) had previously received treatment with interferon in 85 (57 p. 100) and/or Velbe in 43 (29 p. 100). 319 cutaneous localisations were treated, 59 p. 100 by extended cutaneous irradiation, using 4 and/or 8 MeV electron beam energy, and 41 p. 100 by localized irradiation, using 45 kVX-ray energy, 2.5 Gy/fraction, 4 times a week by split course 20 Gy then 10 Gy two weeks later. Twenty patients (13 p. 100) with oedema of the lower limbs were treated, using 4 MV photon therapy with bolus, and 3 (2 p. 100) were treated for lesions in the ENT regions. Only 131 patients were evaluable (257 localisations); 62 p. 100 obtained complete remission and 31 p. 100 partial remission after a mean period of 1.5 months (0.5-3 months). The overall tolerance was acceptable. The complications were epidermitis with some necrosis (8 p. 100), exudative epidermitis (26 p. 100), moderate epidermitis (63 p. 100) and slight reactions in 4 p. 100. The mean recurrence time was 5 1/2 months. PMID- 2321897 TI - [Recurrent erythema multiforme associated with hypogammaglobulinemia of variable expression]. PMID- 2321898 TI - [Reactive cutaneous angioendotheliomatosis]. PMID- 2321899 TI - [Lateral nail folds of the hallux in infants: a peculiar association]. PMID- 2321900 TI - [Management of cutaneous complications of BCG vaccine]. PMID- 2321901 TI - [Suppurative hidradenitis]. PMID- 2321903 TI - [The school physician and the abused child]. AB - The school physician, together with the school nurse, has special opportunities to detect situations of distress in children, because of his or her contacts with the children themselves, teachers, community social workers and child welfare agencies, family physicians, hospitals, juridical agencies, and families. Follow up of reported cases shows that abused children often fail to receive the consideration they deserve and that the attention they need is often deflected towards the parents and their problems. Too often, the decision not to break up the family transforms the child into a tool and into a test of parental rehabilitation. The child's incontrovertible right to normal growth and development requires that stable protective solutions outside a severely deleterious family environment be more often and more quickly considered. PMID- 2321902 TI - [Kidney functional reserve. An experimental study]. AB - The renal functional reserve (RFR), the increase in glomerular filtration rate (GFR) induced by a protein load, seems to be diminished or even lost in renal failure. Our experimental study was undertaken to determine whether the RFR is lost beyond a given level of nephron reduction, using different protein loads. In the first two studies, RFRs were evaluated during an oral protein load consisting in a high-protein diet (30% casein) compared to a low-protein diet (7% casein). Each diet was given to SD rats (200 g) either for three weeks immediately after nephrectomy (Nx) or for four days one month after Nx. Nx was subtotal and consisted in removal of 65 to 85% of the mass of the renal parenchyma. The GFR evaluated by inulin clearance measurements increased considerably after a prolonged (+188%) or short-lived (+35%) oral protein load if less than 70% of the renal mass had been removed. Beyond this threshold of nephron amputation, the high-protein diet had no effect on the GFR, despite an increase in the residual renal mass (+200% in moderate and severe Nxs). In a third study, the GFR was measured one month after Nx and the effects of an infusion of amino acids (vamine) or of a placebo were compared, each rat serving as his own control. Extent of Nx was 0%, 50%, 65-70%, and 80%. Regardless of the extent of nephron reduction, the GFR increased under vamine, but interindividual variations in each group were marked (+5 to +70%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321904 TI - [The value of alizapride in the treatment of vomiting in infants and children]. AB - An open, three-day trial was carried out in 49 infants and children with vomiting related to an acute gastrointestinal or ENT infection (63.3% of cases), a gastroesophageal reflux (20.4%), or an attack of malaria (14.3%). Mean age of patients was 21.9 months. Number of episodes of vomiting exceeded six per day in 89.8% of patients. Alizapride (Plitican) was given as oral drops in a dosage of 3 mg/kg/d. Five patients were prematurely withdrawn from the trial for clinical deterioration requiring discontinuation of enteral nutrition. Under treatment, vomiting resolved completely in 35 patients, i.e. 71.4% of the initial study group. Six patients exhibited incomplete improvement of vomiting and eight (including the 5 dropouts) continued to have a significant number of episodes of vomiting. Overall effectiveness evaluated on the frequency of episodes of vomiting, weight changes, and the investigator's clinical judgement was considered as excellent or good in 81.6% of cases. No significant adverse effects were recorded but the product's bitter taste was involved in the persistence of vomiting in one of the dropouts and in the development of moderate nausea in another patient who was able to continue treatment. The therapeutic value of alizapride, evaluated using an analog scale, proved significant in this indication. PMID- 2321905 TI - [Early failures in kidney transplantation. A retrospective study of 53 cases]. AB - Among the 652 consecutive renal transplants performed from January 1973 through December 1988, all graft failures within 60 days of transplantation were retrospectively analyzed. The 53 early failures were divided into four groups on the basis of pathologic findings in the removed transplant). 1) Irreversible vascular rejection (17 cases); in ten patients, this rejection occurred between the fourth and eight days and was manifested by uniform clinical features. 2) Thrombosis of the renal artery (18 cases), with several subgroups: a) early postoperative thrombosis (5 cases) with primary anuria; b) thrombosis following reoperation (6 cases) for urine leakage or occlusion; c) thrombosis with a clotting disorder,; d) and five cases of thrombosis with clinical manifestations of vascular rejection but with isolated thrombosis upon histologic examination. 3) Thrombosis of the renal vein (12 cases), with primary anuria in nine cases, and rupture of the kidney in three. 4) The last group includes six cases due to a variety of causes: one immediately non-viable -kidney, two severe, irreversible cases of tubulonephritis, one cortical necrosis secondary to circulatory collapse in the recipient, one complete necrosis of the ureter requiring removal of the transplant, and one immediate recurrence of hemolytic uremic syndrome. Among the risk factors for early failure, attention is drawn to the young age of the donor or recipient that increases the risk of thrombosis. Furthermore, the risk of vascular rejection was decreased in patients preventively treated by OKT3. PMID- 2321906 TI - [Treatment of cystinosis using cysteamine]. AB - Eighteen pediatric patients with cystinosis were treated with cysteamine. Treatment was started at a variable age, between 10 months and 7 years, and was continued for 6 months to eight years. Results were evaluated on renal function changes and growth. Whereas 65% of patients with cystinosis develop terminal renal failure before the age of ten years, three (16%) of our 18 patients given cysteamine started dialysis before the age of ten and all three had first received cysteamine only after 4 1/2 years of age. The plasma creatinine level was also lower in treated patients as compared with a control multicenter group. Growth was also significantly improved by treatment, especially in those children treated before the age of 26 months who were taller by 2 SD at age five and 2.5 SD at age eight than untreated controls. Some children who complied strictly with the treatment regimen had an normal stature (- 1 SD) at ten years of age. In conclusion, the effectiveness of cysteamine seems obvious in this group of patients if rigorous compliance with the drug dosing schedule is achieved. PMID- 2321907 TI - [Imaging in ischemic colitis]. PMID- 2321908 TI - [Ischemic colitis: viewpoint of the anatomo-pathologist]. PMID- 2321909 TI - [The value of computerized tomography in the assessment of hepatic iron overload in genetic hemochromatosis]. AB - The aim of the present study was to evaluate the effectiveness of single-energy computed tomography in determining iron overload in idiopathic hemochromatosis, with special reference to slightly overloaded cases. Liver attenuation was determined in 100 patients (46 cases of idiopathic hemochromatosis, 32 cases of chronic liver disease, and 22 normal controls). The iron load was determined for the first two groups by biochemical determination of liver iron concentration (performed in all but 12 subjects in the chronic liver disease group) and hepatic histologic grading. The main results for liver attenuation (upper normal limit, 72 Hounsfield units) showed that despite a high specificity (0.96), this parameter was of low sensitivity (0.63). Although mean liver attenuation in idiopathic hemochromatosis (77 +/- 14) was significantly higher than in chronic liver diseases (53 +/- 17; p less than 10(-4], and normal controls (66 +/- 3; p less than 10(-3], and despite an overall good correlation between liver attenuation and liver iron concentration (r = 0.72; p less than 10(-3], liver attenuation was unable to detect moderate iron overload. Fourteen of 18 patients with a liver iron concentration of less than 150 mumol/g dry liver wt had liver attenuation values of less than 72. Moreover, 3 of 18 subjects with a liver iron concentration of greater than 150 had a liver attenuation of less than 72. Of these 17 false-negatives, only 7 could be attributed to associated steatosis. On the whole, single-energy computed tomography, when used on a routine basis for diagnosing iron overload, is of limited clinical value in idiopathic hemochromatosis due to its poor sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2321910 TI - Common glucose-6-phosphate dehydrogenase (G6PD) variants from the Italian population: biochemical and molecular characterization. AB - By biochemical characterization of glucose-6-phosphate dehydrogenase (G6PD) from the red cells of seventeen subjects of the population of Matera (Southern Italy) we have identified six genetically determined common variants. Among these, G6PD Metaponto and G6PD A(-) Matera had been already fully characterized. We have now found that A(-) Matera is genetically heterogeneous since one of two subjects examined had the two mutations at codons 68 and 126 characteristic of a typical A(-) variant, while the other subject had only the codon 126 mutation. G6PD Pisticci and G6PD Tursi are two new variants whose molecular lesion is not yet known. G6PD Cagliari-like has biochemical characteristics reminiscent of G6PD Cagliari, isolated in Sardinia, and was found to have the same nucleotide substitution as G6PD Mediterranean. G6PD Montalbano is a new variant, with nearly normal properties, due to a G----A transition which causes an Arg----His amino acid replacement at position 285. PMID- 2321911 TI - The gene for the alpha 2 chain of the human fibrillar collagen type XI (COL11A2) assigned to the short arm of chromosome 6. AB - A cosmid clone (CosHcol.11) containing the alpha 2(XI) collagen gene (COL11A2) has been isolated. The gene contains conserved DNA and amino-acid sequences characteristic of fibril forming collagen, which is in accordance with the classification of type XI collagen as a fibrillar collagen. The genomic clone containing the alpha 2(XI) gene has been used as probe in the Southern blot analysis of DNA from a panel of human/hamster somatic cell hybrids containing different numbers and combinations of human chromosomes. Synteny analysis revealed that only chromosome 6 showed complete concordant segregation with COL11A2. Furthermore, the gene was regionally mapped to the short arm of chromosome 6 by using a hybrid which contained only the long arm of the chromosome. PMID- 2321912 TI - Isolation and use of chromosome 1 probes for linkage studies on Charcot-Marie Tooth disease. AB - Nine probes were isolated from a human chromosome 1 enriched library and mapped to regions of chromosome 1 using somatic cell hybrid lines. One clone, LR67, which mapped to 1q12----q23 detected a BglI RFLP. This probe, as well as 4 other known chromosome 1 markers, alpha-spectrin, Factor XIIIB, DR10 and DR78, were used for linkage studies in 15 Charcot-Marie-Tooth disease (CMT1) families. Close linkage of CMT1 to any of the 5 markers was not indicated. Total lod scores excluded linkage of CMT1 to LR67 and to DR10 at 5 cM or less, to DR78 at 10 cM or less, alpha-spectrin at 15 cM or less and Factor XIIIB at 20 cM or less. Possible linkage, however, was shown between LR67 and CMT1 at a distance of 30 cM. Also linkage at a distance of 5 cM was detected between this probe and alpha-spectrin. PMID- 2321913 TI - Multilocus ordering strategies based on sperm typing. AB - Sperm typing is a promising new approach for fine-structure human gene mapping. We examine three-locus sperm typing and its implications for the estimation of recombination fractions and for locus ordering. In particular, we compare some sequential stopping rules for three-locus assignment and develop methods for approximating their mean stopping times and error probabilities. A stopping rule recently described by Thompson and Boehnke et al. appears to be nearly optimal. Under this rule, one stops sampling as soon as the number of sperm of the least frequent recombinant type is s fewer than the number of sperm of the next least frequent type. We develop a random-walk algorithm and some heuristic formulas for assessing the performance of this rule. Since the broader goal of linkage analysis is to order many more than three loci, we propose a trisection strategy for ordering a new locus relative to an existing ordered set of loci. The crux of the trisection strategy is to restrict attention to the smallest block of ordered loci among which the new locus can fall and to divide this block into thirds for the next comparison. This trisection strategy is optimal in the sense that it has the best worse-case performance of any strategy. When it is applied sequentially to order a collection of loci, it is only nearly optimal, as we demonstrate by specific counter-example. However, it does become asymptotically optimal as the size of the collection increases. PMID- 2321914 TI - Surname versus gene structure of a small isolate. AB - A hierarchical partition of the Wright coefficient of inbreeding (F) is shown for an isolated population (about 2000 inhabitants) from a mountainous region of Tuscany (Italy) with regard to both surnames and genes. At total population level surname variation proves substantially consistent with the observed genetic differentiation of the isolate. Analysis of parental isonymy reveals that the population is structured in subunits and it is concluded that the unit population of the region may be very small, practically coinciding with the village (less than 500 inhabitants). The agreement of 'demographic' and genetic structures is less satisfactory at this level, partly because of subsample size, but we conclude that analysis of surnames may give at least a rough idea of the genetic structure of the population. PMID- 2321915 TI - Comparison of simple and modified Bernstein's methods in estimation of recessive allele frequency in the HLA system. AB - Bias and inefficiency of Bernstein's estimator of the recessive allele frequency in generalized ABO-like systems are important for situations where the frequency is small and the number of codominant alleles is large. A modified Bernstein's estimator of the recessive (Smith, 1967) has much smaller bias and higher efficiency than Bernstein's for large samples. Analogous findings are generally observed for small and moderate samples by Monte Carlo experiments. The modified method is preferred for the recessive frequency in the HLA system. The results are illustrated by numerical examples. PMID- 2321916 TI - [Urinary lithiasis due to triamterene]. AB - Iatrogenic renal stones although rare, must be diagnosed. It is therefore essential to use modern techniques such as infrared spectrophotometry. We report a new case of renal stones due to triamterene. Various predisposing factors are examined, in particular urine acidity and the presence of protein in the stones. PMID- 2321917 TI - [The results of urethro-cervicolysis after surgical over-correction of stress urinary incontinence. Apropos of 10 cases]. AB - Between 1985 and 1988, 10 female patients between the ages of 35 and 76 years, suffering from dysuria after surgical correction of urinary stress incontinence (7 sub-urethral bands, 3 colposuspensions) were observed. The abnormality of the course of the urethra compressed anteriorly against the symphysis pubis, observed on clinical examination and on intravenous pyelography as well as urodynamic investigations allowed this dysuria to be attributed to a cervico-urethral obstruction resulting from over correction during the initial surgical operation. The 10 patients were treated by urethro-cervicolysis (9 out of 10) associated with repeated colposuspension in 3 cases. The overall results were disappointing as although 8 of the 10 patients were improved at 3 month, only 4 out of 9 were still improved at 6 months. These poor results raise the question of the value of combining urethro-cervicolysis with colposuspension and possible VY plasty of the bladder neck. PMID- 2321918 TI - [Transplantation in 1989. The revolution]. PMID- 2321919 TI - [Treatment of urethral stenosis using a pedicled flap of the scrotal skin. Long term results in 16 patients]. AB - The scrotal skin is vascularized in part by means of the superficial perineal branch of the internal pudendal artery. This nutrient pedicle, together with the scrotal skin dependent on it, can be isolated. The urethra is approached via the perineum. The stricture is incised longitudinally right down to the healthy area. The scrotal flap and pedicle are mobilized, and then anastomosed along the edges of the urethra. From March 1983 through April 1987, sixteen patients have been operated. Postoperative results: the mean follow-up for the 16 patients is 60 months with extremes of 24 and 66 months. 13/16 patients show good results (81%). 3/16 patients show poor results with recurrence of the stricture localized at the junction of the flap and healthy urethra. Such recurrences have yielded to treatment, in two cases, by optical urethrotomy and, in the other case, by means of a new scrotal flap. PMID- 2321920 TI - [Radical cystectomy for invasive tumors of the bladder in patients over 70 years of age]. AB - The authors present a series of forty patients operated for invasive bladder tumors by radical cystectomy. All patients were older than 70 and had a complicated medical history. Mortality was 1 in 40 and the morbidity was low. The conclusion is that radical cystectomy is a safe procedure in elderly patients. PMID- 2321921 TI - [Evaluation of the results of the treatment of male urethral stricture with a follow-up of more than 5 years]. AB - 149 cases of urethral stricture were treated in the Urology Department from 1971 to 1984. All of these patients have therefore been treated with a minimal follow up of 5 years. There were 87 cases of post-traumatic stricture, 53 of whom were lost to follow-up during the survey, 8 died and 26 patients were able to be reviewed. The remaining 62 cases consisted of post-infectious strictures, with 37 patients lost to follow-up during the survey, 1 patient who died and 24 patients who were reviewed. The patients reviewed were assessed according to the criteria of the SFU (French Urology Society) survey. Direct vision internal urethrotomy was performed in 33 cases with 18 very good or good results (54%), segmental resection was performed in 10 cases with 7 very good or good results, urethroplasty was performed in 4 cases with 2 good results and 2 urethral dilatations were performed with 2 good results. The failures were essentially treated by more complex surgery (urethroplasty). PMID- 2321922 TI - [Endoscopic urethrotomy. Resection, anastomosis and cutaneous urethroplasty. Results of the Normandy Society of Urology]. AB - Although urethrotomy alone gives poor results at 5 years, these results are greatly improved by repeated urethrotomy. This treatment is particularly useful in patients at risk, especially as it can be easily performed under local anaesthesia. The authors confirm the reliability of resection-anastomoses, the superiority of one-stage urethroplasty over two-stage urethroplasty and the poor prognosis associated with a history of repeated dilatations and infectious aetiology. PMID- 2321923 TI - [5-year treatment results of urethral stenosis using internal urethrotomy in adults]. AB - The authors reviewed the records of 69 patients with a mean age of 51 years treated for single (81%) or multiple (19%) urethral strictures, in whom the first operation to be performed was endoscopic internal urethrotomy with a follow-up of at least 5 years. The mean follow-up was 71 months. The actuarial rate of good results was 27.2 +/- 11% at 5 years. The success rate of repeated internal urethrotomy was satisfactory, but was not evaluated with the same follow-up (62.5% after the first repeat urethrotomy with a mean follow-up of 13 months). PMID- 2321924 TI - [Long-term evaluation of the treatment results of male urethral stenosis]. AB - 287 urethral strictures were treated between 1974 and 1984. Two-stage urethroplasty provided 47.6% of good results at 5 years, although there was a possibility of very delayed recurrences. Endoscopic urethrotomy only gave 26% of good results at 5 years, while 30% of good results were obtained after dilatation with Olbert's sound. Endourethral techniques do not compete with two-stage urethroplasty, provided they are performed repeatedly. PMID- 2321925 TI - [Internal urethrotomy. Resection of urethral stricture (over 5 years follow-up)]. AB - Since 1980, in addition to internal urethrotomy, the authors have used urethrotomy combined with endoscopic resection of the stricture. This method consists of a classical first stage of section of the stricture, but only at 11 o'clock and at 1 o'clock to leave a rail of midline fibrosis. The second stage consists of resection of this rail. The value of this approach consists of more effective excision of the fibro-inflammatory callus. Thirty-four patients treated by this method have a follow-up exceeding 5 years. This series was compared with a series of patients treated by internal urethrotomy alone (39 patients with a follow-up greater than 5 years). Very good results were obtained in 55% of cases versus 28% with internal urethrotomy alone. Poor results were obtained in 32% of cases versus 43%. Internal urethrotomy therefore appears to be more rapidly and more completely effective. PMID- 2321926 TI - [Long-term results of male urethral stenosis]. AB - Long-term outcome in 142 patients after endoscopic or surgical treatment or urethral stenosis were evaluated. Results seem disappointing. Development of new therapeutic methods is desirable: the principle of use of an endoprosthetic material for stenoses of the bulbar urethra is described, and the operative technique and preliminary results are reported. PMID- 2321927 TI - [Long-term results of urethrectomy following termino-terminal urethrorrhapy for urethral stenosis. A study of 18 cases]. AB - Urethrectomy followed by terminoterminal urethrorraphy is one of the oldest surgical techniques for treating short urethral stenoses, regardless of their location. Eighteen patients managed by this technique were followed-up for at least ten years. Results were satisfactory in four out of every five cases and success was nearly immediate. No delayed deteriorations were seen. These limitations are mainly related to the length of the lesion. PMID- 2321928 TI - Manganese as a controlling factor in mixed cultures of Lactobacillus plantarum and Enterobacteriaceae. AB - Addition of manganese, at levels of 50 ppm, to a liquid growth medium simulating adverse silage conditions had no effect on the growth or on the fermentation pattern of Enterobacter cloacae and Proteus vulgaris. Yet, the manganese strongly enhanced the growth of Lactobacillus plantarum. Co-cultures of L. plantarum and E. cloacae or P. vulgaris were, by addition of manganese ions, significantly altered in the favour of the former. This finding can be of use in mixed cultures where Enterobacteriaceae act as spoiler microorganisms. PMID- 2321929 TI - Growth stimulation of Treponema denticola by periodontal microorganisms. AB - Previous experiments have indicated that enrichment of subgingival plaque in human serum can lead to the accumulation of Treponema denticola. T. denticola depends on bacterial interactions for its growth in serum. Aim of the present study was to identify specific microorganisms involved in the growth stimulation of T. denticola. To this end, strains isolated from previous plaque enrichment cultures were tested for growth stimulation in co-cultures with T. denticola. In addition, growth of T. denticola was tested in culture filtrates of the same strains, Bacteroides intermedius, Eubacterium nodatum, Veillonella parvula and Fusobacterium nucleatum were found to enhance growth of T. denticola in co cultures. A continuous co-culture of T. denticola, F. nucleatum and B. intermedius in human serum gave very high levels of T. denticola, up to 3.10(9).ml-1. Mechanisms involved in growth stimulation may include the ability of B. intermedius and E. nodatum to cleave the protein-core of serum (glyco )proteins, making these molecules accessible for degradation by T. denticola. In addition, E. nodatum was found to produce a low-molecular weight growth-factor for T. denticola, that was heat-stable and acid as well as alkaline resistant. V. parvula may provide peptidase activities complementary to those of T. denticola. The nature of the growth enhancing activity of F. nucleatum is yet unknown. The data support the dependency of T. denticola on other bacterial species for growth in the periodontal pocket. PMID- 2321931 TI - Modes of lactose uptake in the yeast species Kluyveromyces marxianus. AB - Twelve lactose-assimilating strains of the yeast species Kluyveromyces marxianus and its varieties marxianus, lactis and bulgaricus were studied with respect to transport mechanisms for lactose, glucose and galactose, fermentation of these sugars and the occurrence of extracellular lactose hydrolysis. The strains fell into three groups. Group I (two strains): Fermentation of lactose, glucose and galactose, extracellular lactose hydrolysis, apparent facilitated diffusion of glucose and galactose; Group II (two strains): Lactose not fermented, glucose and galactose fermented and transported by an apparent proton symport, extracellular hydrolysis of lactose present (one strain) or questionable; Group III (eight strains): Lactose, glucose and galactose fermented, lactose transported by an apparent proton symport mechanism, extracellular hydrolysis of lactose and transport modes for glucose and galactose variable. PMID- 2321930 TI - The effects of deoxycholate and sodium dodecyl sulphate on the serological reactivity of antigens isolated from six Bacteroides reference strains. AB - The detergents sodium dodecyl sulphate (SDS) and sodium deoxycholate (NaD) are frequently used as solvents for macromolecular polysaccharide complexes in immunochemical and serological techniques. The influence of the disaggregating surfactants on the serological reactivity of endotoxins isolated from six serotype specific reference strains of the Bacteroides fragilis group was investigated by comparing haemagglutinating and precipitating reactivities of antigen solutions in phosphate buffered saline (PBS), NaD and SDS. All antigens were phenol/water extracted endotoxins. Solutions of antigens isolated from serotypes A, B, C and D in PBS exhibited mainly serotype specificity and a few well known low-titer cross reactions; solutions in NaD showed additional cross reactivity, which was enhanced by solubilization of the antigens in SDS. In immunoelectrophoresis endotoxins isolated from serotypes A and C and dissolved in NaD or SDS showed additional precipitation lines compared to solutions of the same antigens in PBS. These changes in the serological reactivity are of relevance for investigations where the serological specificity of antigens is in question. PMID- 2321932 TI - A non-passive mechanism of butyrate excretion operates during acidogenic fermentation of methanol by Eubacterium limosum. AB - The inhibitory effects of organic acids produced as fermentation end-products during methylotrophic growth of the acidogenic anaerobe, Eubacterium limosum have been investigated. Precise quantification of the intracellular concentrations of acetate and butyrate, together with delta pH measurements indicate that butyrate efflux cannot be explained by a process of passive diffusion. Intracellular concentrations of butyrate were significantly lower than those of the culture broth. It is argued that growth inhibition by butyrate is due to energetic limitations resulting from the energy drain associated with this non-passive efflux mechanism. PMID- 2321933 TI - Uptake of oxygen, release and degradation of hydrogen peroxide by Streptococcus mutans NCTC 10449. AB - Streptococcus mutans NCTC 10499 was cultured under glucose limitation in a chemostat at varying oxygen supply. The rates of oxygen uptake and hydrogen peroxide degradation by cells from the cultures were measured polarographically using a Clark electrode. Oxygenation of the chemostat culture led to adaptation of the organism to oxygen, in that the maximum oxygen uptake rate of the cells was higher when the cells were grown at higher rate of oxygen supply. It is noted that anaerobically grown cells still exhibited significant oxygen uptake. The rate of oxygen uptake followed saturation-type kinetics and Ks values of cells for oxygen were in the micromole range. Hydrogen peroxide accumulation was not observed in aerated chemostat cultures. However, anaerobically grown cells accumulated H2O2 when exposed to oxygen. Cells from aerated cultures did not accumulate hydrogen peroxide. This may be explained by the fact that the rate of hydrogen peroxide degradation was consistently higher than the rate of oxygen uptake. PMID- 2321934 TI - Influence of the blood group reactive substances in saliva on the aggregation of Streptococcus rattus. AB - The interaction of blood group reactive substances in saliva with bacteria was investigated by testing saliva from persons with different blood groups in a bacterial aggregation assay with Streptococcus rattus HG 59, originally S. rattus BHT. For blood group A, saliva from 10 persons out of 11 aggregated S. rattus and for blood group O, saliva from 10 persons out of 16 aggregated S. rattus. For blood group B, saliva from 6 persons out of 8 aggregated S. rattus weakly and the average aggregation activity of blood group B was much lower than for blood group A or O. In addition, saliva from 3 non-secretors did not aggregate S. rattus. The role of blood group antigens in bacterial aggregation was confirmed by inhibition studies with blood group specific sugars and various other sugars. GalNAc, specific for blood group A, inhibited bacterial aggregation by saliva whereas D galactose, specific for blood group B, and D-fucose, specific for blood group O, did not. In addition, sialic acid, a major terminal sugar residue in mucins, also inhibited the bacterial aggregation. This study shows that the blood group and secretor status of a person may influence the interaction of saliva with bacteria in the oral cavity. PMID- 2321935 TI - Alternative respiration pathways in Schwanniomyces castellii. II. Characteristics of oxidation pathways. AB - By using cytochrome-deficient mutants of Schwanniomyces castellii found previously, we measured the inhibition constants of azide and SHAM-alone or combined-for the different oxidative pathways, in order to determine the more suitable concentrations of inhibitors. This allowed us to measure the real capacity of each pathway. We calculated their affinity for oxygen, and determined that O2 was preferencially reduced by the cytochromic pathway, then by the SHAM sensitive pathway, and finally by the SHAM+AA-insensitive pathway. PMID- 2321936 TI - Yeasts and fungi occurring in ensiled whole-crop maize and other ensiled vegetable crops. AB - The yeast flora of whole-crop maize ensiled for two weeks was predominated by Candida holmii, C. lambica, C. milleri, Hansenula anomala and Saccharomyces dairensis. Inoculation with other yeast species reported in the literature to prevail in maize or wheat silages did not alter the yeast flora. At 25 or 30 degrees C the ascomycetous fermentative species found at 20 degrees C were accompanied with ascomycetous non-fermentative fungi, i.c. Exophiala jeanselmei and Verticillium psalliotae, by the non-fermentative imperfect basidiomycetous yeast Rhodotorula mucilaginosa and by the weakly fermentative imperfect ascomycetous yeast Trichosporon adeninovorans. The yeast flora of other vegetable crops, ensiled at 20 degrees C for two weeks, was predominated by the same species that prevailed in ensiled maize, provided the crop did not contain mustard oils or menthol. If these compounds occurred in the crops, the yeast flora was predominated by nonfermentative species like Candida famata, Stephanoascus ciferrii, Rhodotorula minuta, Rh. rubra and Trichosporon cutaneum. PMID- 2321937 TI - Utilization of mucin by oral Streptococcus species. AB - The ability of oral Streptococcus strains to utilize oligosaccharide chains in mucin as a source of carbohydrate was studied in batch cultures. Pig gastric mucin, as a substitute of human salivary mucin, was added to chemically defined medium containing no other carbohydrates. Strains of S. mitior attained the highest cell density, while mutans streptococci: S. mutans, S. sobrinus, S. rattus, grew very little in the medium with mucin. S. mitis, S. sanguis, and S. milleri in decreasing order, showed intermediate growth. Mucin breakdown as measured by sugar analyses indicated that oligosaccharide chains were only partially degraded. Every strain produced one or more exoglycosidases potentially involved in hydrolysis of oligosaccharide. The enzyme activities occurred mainly associated with the cells, and very little activity was found in the culture fluids. The relationships between glycosidase activities and growth, or mucin degradation were not always clear. PMID- 2321938 TI - Re-examination of cellular cyclic beta-1,2-glucans of Rhizobiaceae: distribution of ring sizes and degrees of glycerol-1-phosphate substitution. AB - Gel-filtration and thin layer chromatography of low molecular weight carbohydrates from culture filtrates of Agrobacterium radiobacter, Isolate II, have shown, that next to the neutral beta-1,2-glucan fraction a major acidic fraction was present which was found to be glycerophosphorylated cyclic beta-1,2 glucans. Re-examination of cyclic beta-1,2-glucan preparations which had been obtained by extraction of Rhizobium cells with hot phenol-water also showed these acidic modified beta-1,2-glucans to be present. Cyclic beta-1,2-glucans from R. leguminosarum (9 strains) and of R. phaseoli (1 strain) had ring size distribution with degrees of polymerisation (DPs) of 19 and 20 as major ring sizes of which a minor part was glycerophosphorylated; beta-1,2-glucans of R. trifolii (3 strains) had ring sizes with DPs measuring 19-22 as prominent components which were largely unsubstituted, and R. meliloti (7 strains) had beta 1,2-glucans with ring size distributions extending to still higher DPs of 19-25 of which the major part appeared to be glycerophosphorylated. PMID- 2321939 TI - Nursing diagnoses. Their use in developing care plans. PMID- 2321940 TI - Females in the workplace. Acknowledging, preventing betrayal. AB - The only way that backstabbing will be stopped is if women work together. All women must work toward: developing confidence in themselves; extending a hand to help others; taking the risk to be overt; confronting backstabbers and not letting them be role models; communicating with each other the lessons they learn, and becoming positive role models. No matter how badly you have been hurt, you need to claim the gift of compassion for yourself and for others. You need to build a strong and supportive network that will not tolerate covert action, and that supports and rewards overt behavior. It is an important step to becoming a happy and fulfilled woman in the workplace. PMID- 2321941 TI - Recommended practices. Safe care through identification of potential hazards in the surgical environment. AORN Technical Practices Coordinating Committee. PMID- 2321942 TI - Informed consent for blood transfusions; conducting AIDS tests without consent; donating care to medically indigent. PMID- 2321943 TI - Keeping staff up to date on information. PMID- 2321944 TI - Nurses' liability for inaccurate counts. PMID- 2321945 TI - Perioperative nurses should keep monitoring within their specialty. PMID- 2321947 TI - State nurses' associations, not trade unions, should represent nurses at the bargaining table. PMID- 2321946 TI - Abdominal surgery studied in patients with AIDS. PMID- 2321948 TI - Anterior cruciate ligament reconstruction. Using patellar tendon grafts. PMID- 2321949 TI - Gastrointestinal end-to-end anastomosis. Using staples to secure the procedure. PMID- 2321950 TI - Pediatric intraoperative radiation. Hospitals share resources to provide care. PMID- 2321951 TI - 13C NMR study of the interrelation between synthesis and uptake of compatible solutes in two moderately halophilic eubacteria. Bacterium Ba1 and Vibro costicola. AB - The synthesis and uptake of intracellular organic osmolytes (compatible solutes) were studied with the aid of natural abundance 13C NMR spectroscopy in two unrelated, moderately halophilic eubacteria: Ba1 and Vibrio costicola. In minimal media containing 1 M NaCl, both microorganisms synthesized the cyclic amino acid, 1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid (trivial name, ectoine) as the predominant compatible solute, provided that no glycine betaine was present in the growth medium. When, however, the minimal medium was supplemented with glycine betaine or the latter was a component of a complex medium, it was transported into the cells and the accumulating glycine betaine replaced the ectoine. In Ba1, grown in a defined medium containing glucose as the single carbon source, ectoine could only be detected if the NaCl concentration in the medium was higher than 0.6 M; the ectoine content increased with the external salt concentration. At NaCl concentrations below 0.6 M, alpha,alpha-trehalose was the major organic osmolyte. The concentration of ectoine reached its peak during the exponential phase and declined subsequently. In contrast, the accumulation of glycine betaine continued during the stationary phase. The results presented here indicate that, at least in the two microorganisms studied, ectoine plays an important role in haloadaptation. PMID- 2321952 TI - Calcium- and cysteine-participatory oxidative formation of albumin-copper complex. AB - An albumin-copper-cysteine complex that has been shown to be formed in serum when cupric ion is injected intravenously into rats was reconstituted in vitro with mercaptalbumin, cupric ion, and cysteine in the presence of calcium ions. Mercaptalbumin was separated from fresh rat serum on a GS-520P column and the protein was incubated with an equimolar amount of cupric ions, which resulted in the formation of an albumin-copper complex. However, the albumin-copper complex did not form the albumin-copper-cysteine complex in the presence of cysteine at any of the molar ratios of cysteine to mercaptalbumin examined. Albumin-copper cysteine complex was formed only when a more than equimolar amount of calcium to mercaptalbumin was present in the incubation mixture. The stoichiometric relationship revealed for the formation of albumin-copper-cysteine complex is mercaptalbumin: copper:cysteine:calcium = 1:1:2:1. One molar equivalent of cysteine was incorporated into the complex through disulfide bonds and another molar equivalent of cysteine was present unchanged after the reaction, suggesting that the latter cysteine participated in maintaining a specific conformation of albumin during formation of the complex. The overall reaction was oxidative and oxygen enhanced the reaction. PMID- 2321953 TI - Analogs of oxalacetate as potential substrates for phosphoenolpyruvate carboxykinase. AB - Structural analogs of the substrate oxalacetate were examined as potential substrates and inhibitors for chicken liver mitochondrial phosphoenolpyruvate (P enolpyruvate) carboxykinase. Steady-state kinetics were employed to characterize the inhibitory effects of these substrate analogs with the enzyme. Assays were carried out in both carboxylation and decarboxylation reaction directions. Pyruvate, beta-hydroxypyruvate, beta-mercaptopyruvate, beta-fluoropyruvate, DL lactate, glycolate, glycoaldehyde, glyoxylate, glyphosate, and DL-aspartate showed no inhibitory effects by steady-state kinetics. Oxalate, acetopyruvate, and DL-, D-, and L-glycerate exhibited weak noncompetitive inhibition of the P enolpyruvate carboxykinase-catalyzed reaction. DL-3-Nitro-2-hydroxypropionic acid, 3-nitro-2-oxopropionic acid, DL-malate, malonate, tartronate, and alpha ketobutyrate all show weak inhibition with estimated inhibition constants greater than 20 nM. Several of these compounds were investigated by 31P NMR to determine if they function as phosphoryl acceptors for GTP. None of the compounds tested act as phosphoryl acceptors in the enzyme-catalyzed reaction. Chicken liver mitochondrial phosphoenolpyruvate carboxykinase shows a remarkably high degree of specificity at the binding site of oxalacetate. PMID- 2321954 TI - Cholesterol distribution in rat liver and brain mitochondria as determined by stopped-flow kinetics with filipin. AB - Recently, analysis of protein distribution in rat brain mitochondria suggested the existence of distinct cholesterol domains in the outer membrane (Dorbani et al., 1987, Arch. Biochem. Biophys. 252, 188-196) while such domains were not detected in rat liver mitochondria (Jancsik et al., 1988, Arch. Biochem. Biophys. 264, 295-301). We studied cholesterol distribution in both types of mitochondria by analyzing the kinetics of filipin-cholesterol complex formation, using the stopped-flow technique. In liver mitochondria, the kinetics are characterized by a biphasic curve which presumably corresponds to the two membranes. This was confirmed by the finding that pretreatment with digitonin abolished one of the kinetic components. Sonication of the mitochondria increased the rate of the filipin-cholesterol complex formation and also abolished one of the two components. In the case of brain mitochondria, several distinct cholesterol domains could be revealed: one of them was cholesterol-free and it was directly accessible to filipin. Two other domains were revealed by differences found in the rate of the cholesterol-filipin complex formation. It is noteworthy that only a part of the cholesterol is accessible to filipin. Sonication of mitochondria decreased the proportion of cholesterol molecules accessible to filipin. This suggests specific interactions of cholesterol with other mitochondrial components, which occur only in brain mitochondria. PMID- 2321955 TI - Factor analysis of the near-ultraviolet absorption spectrum of plastocyanin using bilinear, trilinear, and quadrilinear models. AB - Factor analysis was used to resolve the spectral components in the near-uv absorption spectrum of plastocyanin. The data set was absorption as a function of four variables: wavelength, species of plastocyanin, oxidation state of the copper center, and environmental pH. The data were fit with the traditional bilinear model, as well as with trilinear and quadrilinear models. Trilinear and quadrilinear models have the advantage that they uniquely define the components, avoiding the indeterminacy of bilinear models. Bilinear analysis using the absorption spectra of tyrosine and copper metallothionein as targets resulted in a two-component solution which was nearly identical to that obtained using trilinear and quadrilinear models, for which no targets are required. The two component models separate the absorption into tyrosine and copper center components. The absorption of tyrosine is found to be pH dependent in reduced plastocyanin, and the absorption magnitude of the reduced copper center is the same in the four different plastocyanin species. Further resolution is provided by a three-component quadrilinear model. The results indicate that there are at least two different electronic transitions which cause the absorption of the reduced copper center and that one of them couples to a tyrosine residue. It is the absorption of this coupled tyrosine residue which is pH dependent. Correlation of the results with previous studies indicates that it is Tyr 83 which is the perturbed residue. The separation of the absorption of the copper center and Tyr 83 provides spectroscopic probes for the conformations of the north pole and east face reaction sites on the plastocyanin protein. PMID- 2321956 TI - Changes in the amount of cytochrome P450s in rat hepatic microsomes with starvation. AB - The effects of starvation on the composition of 12 different cytochrome P450s in rat hepatic microsomes were studied with a specific antibody. Changes in the metabolic activity of the microsomes were studied at the same time. P450 DM (P450j) was induced 2.5-fold by a 48-h starvation and its increase reflected the increase of metabolic activity of hepatic microsomes toward aniline, 7 ethoxycoumarin, and N-nitrosodimethylamine. P450 K-5, the major renal cytochrome P450 in untreated male rat, was also induced 2.5-fold by a 48-h starvation. P450 UT-2 (P450h) and P450 UT-5 (P450g), typical male-specific forms, decreased with starvation. P450 UT-2 had high testosterone 2 alpha- and 16 alpha-hydroxylation activities. These activities of hepatic microsomes were reduced with the decrease in P450 UT-2. P450 PB-1, testosterone 6 beta-hydroxylase, was increased time dependently by starvation. P450 UT-4 (RLM2), a minor male-specific form, was not changed by starvation. P450 PB-2 (P450k), present in both sexes, was changed little by starvation. P450 PB-4 (P450b) and P450 PB-5 (P450e) are strongly induced in rat liver by phenobarbital in coordinate fashion. Starvation increased P450 PB-4 12-fold but reduced P450 PB-5 to 22% of the control level. P450 MC-1 (P450d) was decreased by starvation. P450 MC-5 (P450c) was barely detected in control rats and was not changed by starvation. P450 IF-3 (P450a), rich in immature rats, was increased by starvation, accompanied by an increase in testosterone 7 alpha-hydroxylation activity in the hepatic microsomes. We further investigated whether new cytochrome P450s appeared upon starvation by comparison of chromatographic profiles of cytochrome P450 from starved rats with those of cytochrome P450 from control rats using HPLC. Three new cytochrome P450s were detected in the starved rats. These cytochrome P450s were purified to homogeneity. One of them was P450 DM, judging from spectral properties, catalytic activity, and the NH2-terminal sequence. The two other forms were designated P450 3b and 4b. The minimum molecular weights of P450 3b and 4b were 53,000 and 52,000, respectively, and their CO-reduced absorption maxima were at 449 and 452 nm, respectively. P450 3b metabolized aminopyrine, N-nitrosodimethylamine, 7 ethoxycoumarin, and lauric acid, but with low activity. P450 4b was efficient in lauric acid omega- and (omega-1)-hydroxylation only. The spectral properties, catalytic activity, peptide map, and NH2-terminal sequence of P450 4b agreed with those of P450 K-5. P450 3b was a new cytochrome P450, judged by these criteria. PMID- 2321958 TI - Temperature dependence of Na+/Ca2+ exchange activity in beef-heart sarcolemmal vesicles and proteoliposomes. AB - Temperature dependence of Na+/Ca2+ exchange activity was studied in beef cardiac sarcolemmal vesicles in the absence and presence of the inhibitor amiloride and in proteoliposomes reconstituted with different lipid mixtures. Arrhenius plots for Na+/Ca2+ exchange activity in both control and amiloride-treated vesicles revealed an apparent energy of activation of 9665 +/- 585 (SE, n = 4) cal/mol, corresponding to a temperature coefficient (Q10) value of 1.70 +/- 0.05 (SE, n = 4) over the range 25-37 degrees C. When Na+/Ca2+ exchange was reconstituted into phosphatidylcholine (PC):phosphatidylserine (PS) (52:48, mol/mol), PC:PS:cholesterol (25:39:36, mol/mol), and PC:PS:distearoylphosphatidylcholine (DSPC) (31:48:21, mol/mol) proteoliposomes, the highest activity was found in PC:PS:cholesterol proteoliposomes. Arrhenius plots of Na+/Ca2+ exchange activity exhibited breakpoints at 23 degrees C (PC:PS), 33 degrees C (PC:PS:cholesterol), and 23 degrees C (PC:PS:DSPC). The increase in the thermotropic transition temperature with cholesterol could result from the condensing effect of this sterol, whereas the breaks observed with PC:PS and PC:PS:DSPC could be caused by a non-lipid-mediated membrane protein conformational change. These results indicate that the lipid microenvironment around the Na+/Ca2+ exchanger and the nature of the specific lipid-protein interactions influence the activity of this antiporter. Further evidence supporting the hypothesis that cholesterol behaves as a specific positive effector for the exchanger is also given. PMID- 2321957 TI - Plants contain multiple biotin enzymes: discovery of 3-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase and pyruvate carboxylase in the plant kingdom. AB - Acetyl-CoA carboxylase is the sole biotin enzyme previously reported in plants. Western analysis with 125I-streptavidin of proteins extracted from carrot somatic embryos visualized six biotin-containing polypeptides, the relative molecular masses of which are 210,000, 140,000, 73,000, 50,000, 39,000, and 34,000. This multiplicity of the biotin-containing polypeptides can be partly explained by the discovery of 3-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase, and pyruvate carboxylase in extracts of somatic carrot embryos, biotin enzymes previously unknown in the plant kingdom. These biotin enzymes seem to be widely distributed in the plant kingdom. PMID- 2321959 TI - Substrate-mediated purification and characterization of a 3-hydroxybenzoic acid-6 hydroxylase from Micrococcus. AB - 3-Hydroxybenzoic acid-6-hydroxylase from Micrococcus sp. was purified to homogeneity in a single step using the substrate-mediated interaction of the enzyme with blue-Sepharose. The enzyme was bound to the affinity matrix in the presence of 3-hydroxybenzoic acid and was eluted in its absence. The molecular weight of the purified enzyme is 70,000 with no subunit structure. The flavoenzyme required the exogenous addition of FAD for its complete activity and had a strict preference for NADH over NADPH. The activity of the enzyme was drastically inhibited by Cu2+ and Hg2+ and the inhibition was reversed by thiol reagents. PMID- 2321960 TI - Mechanism of pyruvate inhibition of plant pyruvate dehydrogenase kinase and synergism with ADP. AB - The effects of various metabolites on pyruvate dehydrogenase (PDH) kinase catalyzed inactivation of the pyruvate dehydrogenase complex (PDC) were studied in extracts of mitochondria purified from green leaf tissue of Pisum sativum L. Pyruvate was an uncompetitive inhibitor of PDH kinase with respect to ATP whereas ADP was a competitive inhibitor. In the absence of pyruvate a fivefold excess of ADP over ATP was required to inhibit PDH kinase, however, in the presence of pyruvate much lower ADP concentrations were required. Inhibition of PDH kinase by pyruvate and ADP was synergistic and the addition of ADP changed pyruvate from an uncompetitive inhibitor to a noncompetitive inhibitor. This result indicates that pyruvate acts as a "dead-end" inhibitor, binding to the PDH kinase-ADP reaction intermediate. Evidence is also presented that inhibition by pyruvate in the presence of thiamine pyrophosphate is due to the formation of hydroxyethyl thiamine pyrophosphate. The results are discussed in terms of the regulation of PDC activity by pyruvate and ADP during periods of increased demand for carbon skeleton biosynthesis by way of the tricarboxylic acid (TCA) cycle despite constraints imposed on TCA cycle flux by a high ATP/ADP ratio. PMID- 2321961 TI - Prominent stacking interaction with aromatic amino acid by N-quarternization of nucleic acid base: X-ray crystallographic characteristics and biological implications. AB - In order to investigate the mode of interaction between the N-quarternized cytosine base and the aromatic amino acid, the crystal structure of the 3-methyl cytidine-5'-monophosphate:tryptamine complex was analyzed by X-ray diffraction. The complex crystals were stabilized by extensive hydrogen bond formations in which eight independent water molecules per complex pair participated. A prominent stacking interaction, characterized by a parallel alignment of both rings with a separation distance of ca. 3.4 A, was observed between the cytosine base and the indole ring. Combining the present results with X-ray crystallographic data on the adenine--and guanine--aromatic amino acid interactions, we summarize the structural characteristics observed in the stacking interaction of the N-quarternized nucleic acid base with the aromatic amino acid and discuss their biological implications, especially in connection with the significance of N-protonation of nucleic acid base for selective recognition by protein. PMID- 2321962 TI - Clastogenic inosine nucleotide as components of the chromosome breakage factor in scleroderma patients. AB - In the present study, we attempted to identify the chemical nature of the clastogenic factor (CF) from patients with progressive systemic sclerosis (scleroderma). Computerized mass spectrometry of clastogenic fractions obtained by HPLC of plasma ultrafiltrates detected molecular peaks compatible with inosine triphosphate and inosine diphosphate (ITP and IDP). The concomitant detection of IDP, together with ITP, and the absence of these peaks in nonclastogenic fractions and corresponding control fractions are arguments in favor of a biological relevance of these observations. The most important confirmation came from the clastogenic effect of commercial ITP and IDP added to the culture medium of the test cultures. The induction of chromatid type damage by these substances in lymphocytes exposed in the G0 phase of their cell cycle and the prevention of this damage by superoxide dismutase are analogous to the observations with CF. PMID- 2321963 TI - Glycan research on barley, maize, oats, and sorghum grain alpha-amylases: comparison with rice alpha-amylase. AB - alpha-Amylases from germinated maize, oats, rice, and sorghum were isolated by glycogen precipitation and hydrophobic interaction chromatography. Several methods were used for the detection of glycoproteins, including barley alpha amylase isozymes purified as previously described and using the rice alpha amylase as a positive control for glycosylation. Affinoblotting using concanavalin A, immunoblotting using a xylose-specific serum which reacts with complex N-linked glycans, and endo-beta-N-acetylglucosaminidase H treatment of amylases gave negative results for maize, oats, sorghum, and barley. However, after deglycosylation with trifluoromethanesulfonic acid, the molecular weight of one maize alpha-amylase constituent was clearly decreased. The same result was obtained after beta-elimination in mild conditions. Together these results indicated probable O-linked glycosylation of one maize alpha-amylase when barley, oats, and sorghum alpha-amylases did not appear to be glycosylated. Chemical deglycosylation of rice alpha-amylase resulted in the production of two polypeptides with different molecular weights. PMID- 2321964 TI - Stimulation and inhibition of [3H]ryanodine binding to sarcoplasmic reticulum from malignant hyperthermia susceptible pigs. AB - When compared to normal pig sarcoplasmic reticulum (SR), SR from malignant hyperthermia susceptible (MHS) porcine skeletal muscle has been shown to exhibit an increased rate of calcium release, as well as alterations in [3H]ryanodine binding activity in the presence of microM Ca2+ (Mickelson et al., 1988, J. Biol. Chem. 263, 9310). In the present study, various stimulators (adenine nucleotides and caffeine) and inhibitors (ruthenium red and Mg2+) of the SR calcium release channel were examined for effects on MHS and normal SR [3H]ryanodine binding. The apparent affinity of the MHS SR receptor for ryanodine in the presence of 10 mM ATP (Kd = 6.0 nM) or 10 mM caffeine (Kd = 28 nM) was significantly greater than that of the normal SR (Kd = 8.5 and 65 nM in 10 mM ATP or caffeine, respectively), the Bmax (12-16 pmol/mg) was similar in all cases. The Ca2+(0.5) for inhibition of [3H]ryanodine binding in the presence of 5 mM AMPPNP (238 vs 74 microM for MHS and normal SR, respectively) and the Ca2+(0.5) for stimulation of [3H]ryanodine binding in the presence of 5 mM caffeine (0.049 vs 0.070 microM for MHS and normal SR, respectively) were also significantly different. Furthermore, in the presence of optimal Ca2+, MHS SR [3H]ryanodine binding was more sensitive to caffeine stimulation (C0.5 of 1.7 vs 3.4 mM) and was less sensitive to ruthenium red (C0.5 of 1.9 vs 1.2 microM) or Mg2+ inhibition (C0.5 of 0.34 vs 0.21 mM) than was normal SR. These results further support the hypothesis that differences in the ryanodine/receptor calcium release channel regulatory properties are responsible for the abnormal calcium releasing activity of MHS SR. PMID- 2321965 TI - Biogenesis of catalase in glyoxysomes and leaf-type peroxisomes of sunflower cotyledons. AB - Eight charge isoforms of catalase (EC 1.11.1.6.) appeared in the peroxisomes of sunflower cotyledons during growth after germination (2.5 days of dark, continuous light thereafter). In the light, when glyoxysomes were transformed to leaf-type peroxisomes, the five more-basic forms (CAT 1 through CAT 5) became more prominent, while amounts of the three more-acidic forms (CAT 6 through CAT 8) decreased considerably. The isoforms CAT 1 through CAT 5 were hybrids of 55- and 59-kDa subunits, whereas CAT 6 through CAT 8 contained 55-kDa subunits exclusively. The catalase translation products changed during the transition of glyoxysomes to leaf-type peroxisomes. Polyadenylated RNA from 2-day-old cotyledons directed synthesis of 56-kDa subunits, whereas 59-kDa subunits predominated after in vitro translation of RNA from 4-day-old cotyledons. Both translation products were processed to lower molecular weight forms in vivo. The 56-kDa translation products were precursors for 55-kDa subunits in glyoxysomes. It could not be decided however, whether the 59-kDa precursors were processed to 56-kDa or 55-kDa subunits, because both subunits of lower molecular weight were present in leaf-type peroxisomes. Some of the 59-kDa precursors escaped proteolytic processing and formed hybrid isoforms (CAT 1 through CAT 5) with mature 55-kDa subunits. This type of isoform formation, i.e., condensation of mature and unprocessed subunits, has not yet been described for other plant catalases. In summary, the results showed that the postgerminative changes in the number and abundance of catalase isoforms resulted from changes in translation (transcription) of catalase precursors and assembly of proteolytically processed and unprocessed subunits into tetramers within peroxisomes acquiring leaf peroxisomal function. PMID- 2321966 TI - Electrostatic effects on the spectral and redox properties of Clostridium pasteurianum flavodoxin: effects of salt concentration and polylysine. AB - When polylysine is complexed to flavodoxin at low ionic strength, the electrostatic potential of the region which is involved in electron transfer is modified such that positively charged oxidants react more slowly with flavodoxin semiquinone, and negatively charged oxidants react more rapidly. The reaction rate of the uncharged benzoquinone molecule is unaffected. An especially strong effect (approximately 200-fold) occurs with ferricyanide. This is interpreted in terms of electrostatic control of the reaction site. Complexation also changes the conformation of the region around the FMN prosthetic group, which is reflected in the fluorescence and circular dichroism spectra of the protein. PMID- 2321967 TI - Formation of 2-methyltryptophan in the biosynthesis of thiostrepton: isolation of S-adenosylmethionine:tryptophan 2-methyltransferase. AB - L-2-Methyltryptophan was found to be an intermediate in the biosynthesis of the antibiotic thiostrepton. It was isolated from growing cultures and resting cells of Streptomyces laurentii in trapping experiments after the application of labeled L-methionine or L-tryptophan. Its formation from L-tryptophan and S adenosylmethionine was studied in a cell-free extract of S. laurentii. Although several attempts to purify the soluble methyltransferase by standard methods failed, some of its characteristics could be determined in the crude extract. The enzyme has a sharp pH optimum at pH 7.8. The apparent Km value for S adenosylmethionine is 120 microM and the Ki value for S-adenosylhomocysteine is 480 microM. The enzyme is not stereoselective with respect to D- or L-tryptophan, but the D-isomer is converted at a slower rate than the L-isomer. Indolepyruvic acid is also methylated, while indole is not a substrate. The methyl group is transferred with retention of its configuration, contrary to most other methyltransferase reactions. PMID- 2321968 TI - The delta 12-desaturase from the house cricket, Acheta domesticus (Orthoptera: Gryllidae): characterization and form of the substrate. AB - A novel delta 12-desaturase from animals, which converts oleic acid (18:1n-9) to linoleic acid (18:2n-6), was characterized in the house cricket, Acheta domesticus. The delta 12-desaturase product, linoleic acid, was determined by silver nitrate thin-layer chromatography, radio-gas-liquid chromatography and radio-high-performance liquid chromatography with the latter being used for routine analyses. Enzyme activity was located in the microsomal fraction of whole insect homogenates. NADPH or NADH was required for activity, with NADPH being the more efficient electron donor. In short incubation times with oleoyl-CoA as substrate, the highest amount of product, linoleic acid, was found as linoleoyl CoA. With longer incubation periods, most of the linoleic acid was recovered in the polar lipid fraction containing phospholipid. Preincubation of the microsomal preparation in the absence of NADPH, which allowed 90% of the oleoyl moiety to be transacylated into complex lipid, resulted in no detectable desaturation upon addition of NADPH. These data indicate that the oleic acid moiety used as substrate was in the form of a CoA derivative and not in the form of a phospholipid, as it is for the plant delta 12-desaturase. This is the first characterization of a delta 12-desaturase from an animal system and the first report of a delta 12-desaturase that uses oleoyl-CoA as substrate. PMID- 2321970 TI - Iron mobilization from asbestos by chelators and ascorbic acid. AB - The ability of chelators and ascorbic acid to mobilize iron from crocidolite, amosite, medium- and short-fiber chrysotile, and tremolite was investigated. Ferrozine, a strong Fe(II) chelator, mobilized Fe(II) from crocidolite (6.6 nmol/mg asbestos/h) and amosite (0.4 nmol/mg/h) in 50 mM NaCl, pH 7.5. Inclusion of ascorbate increased these rates to 11.4 and 4.9 nmol/mg/h, respectively. Ferrozine mobilized Fe(II) from medium-fiber chrysotile (0.6 nmol/mg/h) only in the presence of ascorbate. Citrate and ADP mobilized iron (ferrous and/or ferric) from crocidolite at rates of 4.2 and 0.3 nmol/mg/h, respectively, which increased to 4.8 and 1.0 nmol/mg/h in the presence of ascorbate. Since ascorbate alone mobilized iron from crocidolite (0.5 nmol/mg/h), the increase appeared to result from additional chelation by ascorbate. Citrate also mobilized iron from amosite (1.4 nmol/mg/h) and medium-fiber chrysotile (1.6 nmol/mg/h). Mobilization of iron from asbestos appeared to be a function not only of the chelator, but also of the surface area, crystalline structure, and iron content of the asbestos. These results suggest that iron can be mobilized from asbestos in the cell by low molecular-weight chelators. If this occurs, it may have deleterious effects since this could result in deregulation of normal iron metabolism by proteins within the cell resulting in iron-catalyzed oxidation of biomolecules. PMID- 2321969 TI - A study of the kinetic mechanism followed by glutathione reductase from mycelium of Phycomyces blakesleeanus. AB - An investigation of the reaction mechanism of glutathione reductase isolated from the mycelium of Phycomyces blakesleeanus NRRL 1555(-) was conducted. The enzyme showed GSSG concentration-dependent substrate inhibition by NADPH and pH dependent substrate inhibition by GSSG. At pH 7.5, the kinetic data were consistent with a basic scheme corresponding to the branching mechanism, involving a ping-pong with formation of a dead-end F.NADPH complex and an ordered sequential mechanism. Both pathways have in common the step in which NADPH binds to the free oxidized form (E) of the glutathione reductase. At low concentrations of GSSG the ping-pong mechanism prevails, whereas at high concentrations the ordered mechanism appears to dominate. The data were analyzed on the basis of the limiting ping-pong mechanism with F.NADPH complex formation and of the hybrid mechanism, and the kinetic constants of the model were calculated. The data obtained at acidic pH values do not rule out the possibility that the kinetic model may be more complicated than the basic scheme studied. PMID- 2321971 TI - Extramitochondrial release of hydrogen peroxide from insect and mouse liver mitochondria using the respiratory inhibitors phosphine, myxothiazol, and antimycin and spectral analysis of inhibited cytochromes. AB - The fumigant insecticide phosphine (PH3) is known to inhibit cytochrome c oxidase in vitro. Inhibition of the respiratory chain at this site has been shown to stimulate the generation of superoxide radicals (O2-), which dismutate to form hydrogen peroxide (H2O2). This study was performed in order to investigate the production of H2O2 by mitochondria isolated from granary weevil (Sitophilus granarius) and mouse liver on exposure to PH3. Other respiratory inhibitors, antimycin, myxothiazol, and rotenone were used with insect mitochondria. Hydrogen peroxide was measured spectrophotometrically using yeast cytochrome c peroxidase as an indicator. Insect and mouse liver mitochondria, utilizing endogenous substrate, both produced H2O2 after inhibition by PH3. Insect organelles released threefold more H2O2 than did mouse organelles, when exposed to PH3. Production of H2O2 by PH3-treated insect mitochondria was increased significantly on addition of the substrate alpha-glycerophosphate. Succinate did not enhance H2O2 production, however, indicating that the H2O2 did not result from the autoxidation of ubiquinone. NAD(+)-linked substrates, malate and pyruvate also had no effect on H2O2 production, suggesting that NADH-dehydrogenase was not the source of H2O2. Data obtained using antimycin and myxothiazol, both of which stimulated the release of H2O2 from insect mitochondria, lead to the conclusion that glycerophosphate dehydrogenase is a source of H2O2. The effect of combining PH3, antimycin, and myxothiazol on cytochrome spectra in insect mitochondria was also recorded. It was observed that PH3 reduces cytochrome c oxidase but none of the other cytochromes in the electron transport chain. There was no movement of electrons to cytochrome b when insect mitochondria are inhibited with PH3. The spectral data show that the inhibitors interact with the respiratory chain in a way that would allow the production of H2O2 from the sites proposed previously. PMID- 2321972 TI - [Shirabu Cancer Symposium--Cancer treatment and host factors]. PMID- 2321973 TI - [The relation between serum carcinoembryonic antigen (CEA) and response to chemotherapy in patients with advanced colorectal cancer]. AB - Prognostic factors from 22 cases of advanced colorectal carcinoma were examined with respect to age, the degree of cellular differentiation, pretreatment serum CEA and doubling time of circulating CEA. The prognoses were very poor for patients of younger age and poorly differentiated tumor. No correlations were observed between survival time and pretreatment serum CEA. A significant correlation of survival time and CEA doubling time was observed. The serial serum CEA levels were examined in the 11 colorectal cancer patients with unresectable multiple liver metastasis, who were treated with intraarterial selective chemotherapy. There were no significant differences between pretreatment serum CEA and survival time on response to chemotherapy. In 9 cases showing over 40 ng/ml of CEA before treatment, however, the serial change in CEA levels correlated well with response to chemotherapy. In four cases with recurrent liver metastasis, prolongation time could be predicted from the CEA induces with respect to the forward time earning and the alternation of the CEA doubling time. Furthermore, the two cases without any measurable lesions also showed the same trend. These results suggested that serial measurement of serum CEA were useful for monitoring the response to chemotherapy against advanced colorectal cancer when the pretreatment serum CEA was high (over 40 ng/ml). PMID- 2321974 TI - [Arterial stasis chemotherapy]. AB - "Arterial stasis chemotherapy" is a concept which summarizes administration methods of anticancer agents under the temporary blockade of the blood flow by any means. The drugs so infused is hardly diluted by blood flow, reaching the tumor tissue in high concentration and staying there much longer than that of administered by simple arterial infusion. "Arterial stasis chemotherapy" contains TAE (transcatheter arterial embolization) with gelatin sponge. TAE with ethiodol, TAE with microencapsulated anticancer drug, BOAI (balloon occluded arterial infusion), arterial administration of SMANCS/Lipiodol, intra-arterial administration of DSM (degradable starch microsphere) and so on. The authors confirmed that anticancer agents, which were soaked in gelatin sponge particles, densely stayed in the tumor for twenty hours after TAE using CT and iodinated contrast media. And we also confirmed a high level of the drug was present selectively in the tumor tissue for a longer time when it was given by BOAI than SAI using scintillation camera and Xe. After these basic studies, we applied TAE and BOAI on the patients with malignant tumors and got much better therapeutic effects than previous reports. We believe therapies based on the concept of "Arterial stasis chemotherapy" will prevail from now on. PMID- 2321975 TI - [Modification of peripheral blood monocytes and T lymphocytes of lymphoid organs by interferon-alpha therapy]. AB - We examined interferon (IFN)-alpha therapy in animal models from the immunological aspects. Long after the cessation of successful IFN administration there found a strong tumor neutralizing activity of spleen T cells in the curing mice. However, this activity was not detectable right after the cessation of IFN administration. Instead, in this early stage, a strong tumor neutralizing activity was found in the lymph nodes of IFN-administered mice. This does not necessarily indicate that the primary modifying target of IFN was T cells since IFN is not capable of directly activating T cells. Further experimentation showed that IFN administration resulted in the very fast production of antitumor monocytes in peripheral blood. Again, this may not be a primary modifying target of IFN since IFN is a very poor activator of monocytes and macrophages and sometimes a very strong nullifier of activation of these cells. Based on these results and those reported in the literatures, it was discussed what would be a real modifying target of IFN in association with the therapeutic effect. PMID- 2321976 TI - [Augmentation of TNF- and lymphotoxin-mediated cytotoxic effect in the combined use of ACNU and involvement of oxygen free radicals]. AB - Roles of oxygen free radicals in recombinant human TNF- and human lymphotoxin (LT)-mediated cytotoxicity have been examined. Nimustine (ACNU), which inhibits glutathione reductase, and buthionine sulphoximine (BSO), an inhibitor of glutathione (GSH) synthesis, were used to modify the steady-state level of intracellular H2O2. TNF-mediated cytotoxicity was augmented when ACNU was added simultaneously to target L cells or Meth A tumor cells. Similar augmented effect was observed when TNF or LT was added to ACNU-treated target cells. However, the addition of GSH nullified the augmentation of TNF-mediated cytotoxicity to ACNU treated Meth A tumor cells. Meth A tumor cells were pretreated with BSO for 24 hr, and thereafter TNF or LT was added in the presence or the absence of BSO. The cytotoxic effect of TNF and LT was augmented by the treatment of the cell with BSO or simultaneous addition of BSO. High degree of the augmentation was obtained when the pretreatment with BSO and further addition of BSO were combined. These results suggest that oxygen free radicals are closely involved in TNF- and LT mediated cytotoxicity and the modulation of intracellular GSH level alters the degree of the cytotoxicity of these cytotoxins. PMID- 2321977 TI - [Lymphocyte subset change during cancer chemotherapy on patients with gastrointestinal, lung and hematopoietic malignancies]. AB - Lymphocyte subsets measured by Ortho-mune on OKT 3, OKT 4A, OKT 8, OKT 10, OKT 11, OKM1, OKB 7, OKB 2 and OKDR were observed before and after chemotherapy on patients with gastrointestinal, lung and hematopoietic malignancies. Almost all patients showed decreased T-cell function expressed by OKT 11 or OKT 3 and suppressor, helper T-cell function expressed by OKT 8 and OKT 4A. In some patients improvement of T-cell function were observed with clinical response and in such cases life span seemed to be longer as expected, and it is supposed that during cancer chemotherapy improvement of T-cell function expressed by OKT series may be important prognostic factors. PMID- 2321978 TI - [Prostaglandin-E2 (PGE2) and interleukin-1 (IL-1) production from plastic adherent peripheral blood mononuclear cells, and serum and urinary glucocorticoid levels in cancer patients treated with systemic chemotherapy--with special reference to circadian rhythm of serum cortisol levels in cancer]. AB - Prostaglandin-E2 (PGE2) and interleukin-1 (IL-1) production from plastic-adherent peripheral blood mononuclear cells stimulated in vitro by bacterial lipopolysaccharide, serum and urinary glucocorticoid levels and the circadian rhythm of serum cortisol levels were studied for better understanding of the immunological and physiological changes produced by systemic chemotherapy in cancer patients. In one responded patient out of four, PGE2 production decreased and IL-1 production increased, whereas the serum cortisol level decreased and the urinary 17-KS excretion level increased. The circadian rhythm of the serum cortisol level was evaluated three times a day, at 7 A.M., 2 P.M. and 10 P.M. Healthy volunteers showed a peak level at 7 A.M. which decreased gradually towards evening and reached to the lowest level at 10 P.M. In contrast, cancer patients showed three additional patterns. These patterns were classified as follows, Type N showed a maximal level at 7 A.M. and minimal level at 10 P.M. as same as in healthy subjects. Type V showed a minimal level at 2 P.M. while type A showed a maximal level at this time. In type F the serum cortisol level was no greater than 1.0 micrograms/dl at any of the three time points. We examined circadian rhythm in four cancer patients treated with systemic chemotherapy. In one PR case, the circadian rhythm shifted from type V to N after the first course of therapy, then changed to type F after subsequent and another courses of the therapy. In another PR case, type N persisted during and after therapy. One MR case shifted from type A to type N. In contrast, one PD case shifted from type N to A. There results suggest that normalization of the circadian rhythm of serum cortisol was associated with the improvement in host body condition achieved by chemotherapy and that systemic chemotherapy modified the immunological and physiological state of cancer patients, as defined above. This may eventually be beneficial for patients. PMID- 2321980 TI - [A mechanism of cisplatin resistance in a cisplatin resistant lung cancer cell line]. PMID- 2321979 TI - [Mechanisms for resistance and cross-resistance patterns of cisplatin-resistant tumor lines]. AB - Mechanisms for cisplatin resistance were studied using mouse leukemias acquired resistance to the drug. Uptakes of cisplatin by L-1210/DDP and P 388/DDP were significantly decreased, compared with the respective sensitive lines. Glutathione contents in both the resistant lines were 1.7 times more than in the respective sensitive ones. While glutathione contents were reduced to about 10% by incubation of cells with D, L-buthionine-S, R-sulfoximine, sensitivity of the resistant cells remained unchanged. Therefore, glutathione might not relate to the mechanism for resistance in these lines. Cross-resistance patterns of L 1210/DDP and P 388/DDP as well as Colon 26/DDP to cisplatin analogs were investigated. Carrier ligands of the analogs, by which antitumor spectra would be controlled, were different from each other and leaving groups were Cl2, as a rule. As a result, L-1210/DDP showed cross-resistance only to two analogs. In contrast, P 388/DDP did so to all complexes tested. The resistance indices to four analogs were more than 50. Colon 26/DDP also showed cross-resistance to all of them, but the degrees of resistance in this line were lower than those in P 388/DDP. These facts revealed that the pattern of cross-resistance was dependent on each cell line and the completely different patterns were shown between the mouse leukemia resistant lines. It was suggested that in developing a new platinum analog, we should select a carrier ligand to which as many resistant lines would show lack of cross-resistance. PMID- 2321982 TI - [Dose intensity and clinical response in patients with advanced gastric carcinoma treated by induced hypertension chemotherapy]. AB - Dose Intensity (DI) was analyzed among 52 eligible and complete patients with advanced gastric carcinoma receiving ADM, 5-FU & MMC (AFM) combination regimen under angiotensin II Induced Hypertension Chemotherapy (IHC). In the induction period DI of CR either in the initial response time or in the effective tumor reduction time was smaller than that of PR, although DI of total period of AFM administration was not different. Based on the evidences, heterogeneous distribution in tumor blood flow under normotension got improved under hypertension by angiotensin II, and chemotherapeutic effects were enhanced. A possibility of the reduction of doses of the drugs administered was suggested. In the maintenance, based on the clinical results, it is mentioned that DI is also useful for an indicator to decide the doses and continuation periods of drugs to be administered. Further investigation on DI will lead to obtain much better maneuver of chemotherapy. PMID- 2321981 TI - [Subrenal capsule assay using nude mice]. AB - Six-day subrenal capsule assay (SRCA) using normal immunocompetent mice developed by Bogden et al. is a promising in vivo chemosensitivity test. This method, however, has a problem of influence of the host reaction. We compared the tumor growth kinetics and host reaction between normal immunocompetent and nude mice. The tumor diameter increased until day 6 in normal and day 16 in nude mice, respectively. However the histological finding revealed many host reactive cells and few viable tumor cells on day 6 in normal mice, and well preserved tumour cells on day 16 in nude mice. These results were supported by flow cytometrical analysis. Then, we examined two immunosuppressive drugs; cyclophosphamide (EX) and cyclosporin A (CSA) in SRCA. The tumors increased in the diameter until day 16 in both EX and CSA-treated groups, but the results of the histological examination showed that tumor cells were preserved in tissue on day 14 in CSA treated and day 6 in EX-treated group. These results were also supported by flow cytometrical analysis. From the investigation of antitumour activities of adriamycin (ADR) and mitomycin C, it was suggested that the 12-day assay was suitable if nude mice were used in SRCA, and six-day assay also, if EX-treated normal mice were used. In CSA-treated group, more toxicity of anticancer drugs was manifested than usual. We studied whether or not CSA had a usefulness in SRCA with normal immunocompetent mice. Sixty mg/kg of CSA was given to BDF1 mice daily SC, and various dosage of ADR was given i.v. on day 2. The body weight of BDF1 mice decreased over 20% within 10 days when ADR was given at more than 5 mg/kg. MX-1, a human breast carcinoma cell line, is known to be sensitive to ADR. This tumor was implanted SC in the back of BALB/c nu/nu mice and chemosensitivity was tested against ADR. ADR resulted to be positive at the dose of 8 mg/kg. On the other hand, the dose of 5 mg/kg proved to be negative, and hence the result of SRCA would be false negative, if the dose of ADR is reduced to avoid the toxicity of CSA. The tumor grew slowly when only 60 mg/kg of CSA was given daily for three weeks, and the inhibition rate was 56.2%. The toxicity of CSA was neglected because the body weight loss was approximately 13%. CSA may have the antitumor effect by itself, and EX did not suppress the host reaction sufficiently.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2321983 TI - [Campylobacter pylori in patients with gastroduodenal disease]. AB - Recent advances of Campylobacter pylori (C. pylori) in human gastric disease and peptic ulcer were reviewed. C. pylori is a microaerophilic, motile, gram negative spiral rod bacterium. And all strains of C. pylori has a strong urease activity. In our experience. 91% of duodenal ulcer, 88% of gastric ulcer and 43% of control have C. pylori associated gastric mucosa. Patients of peptic ulcer with C. pylori infection were high relapse than patients of peptic ulcer without C. pylori, C. pylori is now known to be the most common and important case of pathologic gastritis, and C. pylori infection have been associated with gastric ulcer, duodenal ulcer, and non-ulcer dyspepsia. Although it has been only possible to culture C. pylori for about 6 yr in Japan, there are already sufficient data available to allow us to develop the basic framework that relates C. pylori gastritis to the causation of peptic ulcer disease. PMID- 2321984 TI - [Diagnosis of cancer using lymphocyte electrophoresis (3): Electrophoretic mobility, interleukin 1 and prostaglandin E2 productions of monocytes in peripheral blood of cancer patients]. AB - The S/F ratio of slow electrophoretic mobility cells (less than 0.95 micron/sec/V/cm) to fast mobility cells (greater than or equal to 0.95) increased significantly in the peripheral blood mononuclear cells of cancer patients. Since one of slow mobility cells was mainly composed of monocytes, the relationship between the mobility and the functions of monocytes in the peripheral blood of patients with cancer was examined. The cancer patients (total 27) consisted of 12 patients with rectum, 7 with colon, 3 with stomach, one with ovary and 4 with recurrent cancers and of 3 with stage 1, 11 with stage 2, 3 with stage 3 and 6 with stage 4 + 5. We determined the releases of interleukin 1 (IL-1) and prostaglandin E2 (PGE2) from monocytes, which were stimulated with lipopolysaccharide, as an index for the function of monocytes. The mobility of monocytes and productions of IL-1 and PGE2 from monocytes decreased with the stage of cancer patients, indicating a decreased function of monocytes in the patients. These findings suggest that S/F ratio of the peripheral blood mononuclear cells and mobility, IL-1 and PGE2 productions of monocytes are a good index for the judgement of treatment efficacy of cancer. PMID- 2321985 TI - [A useful combination chemotherapy of cisplatin and etoposide in mediastinal yolk sac tumor]. AB - A 28-year-old male was referred to our hospital because of chest pain and dry cough. Chest x-ray film revealed a tumor mass in the anterior mediastinum indicating invasion into the chest wall and upper lobe of right lung. No tumor was found in the testis. Serum level of alpha-fetoprotein (AFP) was 6,400 ng/ml. Percutaneous biopsy of the tumor suggested yolk sac tumor. The patient was treated with a combination chemotherapy schedule including 30 mg of cisplatin (CDDP) i.v. on Days 1, 2, 3, 4, and 5 and 150 mg of etoposide on Days 1, 2, and 3 as one course therapy. Two courses were employed. Partial response was achieved followed by successful resection of the tumor. This case indicated that a combination chemotherapy CDDP and etoposide combined with surgery could play an active role increasing long-term survival rates in mediastinal yolk sac tumors. PMID- 2321986 TI - [Experience in the use of Kyosera Injection Port as a kind of implantable reservoir (the second report)]. AB - A total of 30 pieces of Kyosera Injection Port, as a kind of implantable reservoir, was used in 29 cases of liver tumor for an intermittent repeated chemotherapy. Of these 27 cases were actually used between Aug. 1st, 1986 and Aug. 31st, 1989. In this paper we studied the safety of the reservoir. The observation period averaged 259.4 days, with the highest of 760 days and the lowest of 29 days. The injection times averaged 12.7 times, with the maximum of 40 times and the minimum of one. The reservoir was placed under the laparotomy, and the cases which underwent cholecystectomy were 93.1%. 16 cases were treated with intraarterial infusion, and 14 with intraportal infusion. We investigated the complication of Kyosera Injection Port in 27 cases. As a result, there were no complication such as catheter occlusion and infection via catheter. But of 27 cases, 8 cases were recognized a complication, and the rate was 29.6%. Lumbago was noted during infusion chemotherapy in three cases, and on the other hand, there were steatolysis and necrosis of the tissue surrounding the implantation site, a movement of port, a catheter out of vessel, a leakage of the drug, and intraabdominal bleeding after taking off the catheter. But of 8 complication cases, only two cases were not able to inject drug. As a result, the rate of complication was 70.4% in over all. On the other hand, of 27 cases, there were 5 cases which recognized the complication caused by reservoir in itself. The safety rate was 81.5%. In such a circumstance this reservoir was very safe and seemed suitable to the implantable reservoir. PMID- 2321987 TI - [A case of pleural effusion secondary to breast carcinoma responding to treatment based upon thoracoscopic findings]. AB - Patients with metastatic breast carcinoma often present symptomatic pleural effusions. A 67-years-old woman, who had undergone right radical mastectomy 7 years previously for right breast carcinoma, developed massive right pleural effusion. Thoracoscopy revealed local metastasis in the center of the parietal mediastinal pleura. On biopsy, it was found to be adenocarcinoma which was considered to have invaded the pleura directly from the mediastinum. She was treated with linac X-ray irradiation focused on the pleural metastasis and systemic chemotherapy (CMF), and resulted in a gradual decrease and final disappearance of the pleural effusion. PMID- 2321989 TI - [New drugs in early clinical trials and drug resistance--US-Japan joint seminar]. PMID- 2321988 TI - [Combination chemotherapy of MCNU and interferon alfa-2a (genetical recombination) for advanced multiple myeloma]. PMID- 2321990 TI - Pustular eruption of pregnancy treated with locally administered PUVA. PMID- 2321991 TI - Frequency of dysplastic nevi among nevomelanocytic lesions submitted for histopathologic examination. Time trends over a 37-year period. AB - All cutaneous nevomelanocytic specimens accessioned for histopathologic examination at Massachusetts General Hospital, Boston, in 1950, 1960, 1970, and 1987 were reviewed. The specimens were categorized as malignant melanoma, acquired or congenital benign nevi, blue nevi, spindle and epithelioid cell nevi, and dysplastic nevi. Other processes such as lentigines were excluded. There was a threefold increase in percentage of patients having nevomelanocytic lesions removed (1.5% in 1950 to 4.6% in 1987) compared with total surgical cases over the 37-year period. A progressive increase in numbers and percentages of dysplastic nevi (among nevomelanocytic surgical cases) was noted over a 37-year interval--2 cases (1% of nevomelanocytic cases) in 1950, 4 cases (2%) in 1960, 23 cases (5%) in 1970, and 189 cases (12%) in 1987. These findings confirm the existence of dysplastic nevi by histopathologic criteria as early as 1950 and illustrate the frequencies of various nevomelanocytic surgical specimens among all surgical specimens at four points in time over a 37-year period at a major referral center for pigmented lesions. PMID- 2321992 TI - Anatomic distribution of acquired melanocytic nevi in white children. A comparison with melanoma: the Vancouver Mole Study. AB - The presence of acquired benign nevi is a risk factor for cutaneous melanoma, yet relatively little is known about the etiology of nevi. We have conducted a study of the prevalence of melanocytic nevi among 1146 white Vancouver (Canada) schoolchildren aged 6 to 18 years. Numbers of nevi per square meter of body surface area increase with age in children of both sexes. Male adolescents have more nevi than female adolescents on the head and neck as well as on the trunk, while prevalence in females is higher on the upper and lower limbs. This distribution parallels that of cutaneous melanoma in British Columbia adults. Nevi are more common in children on intermittently exposed body sites than on constantly or minimally sun-exposed sites. This suggests that exposure to strong intermittent sunlight in childhood (a risk factor for cutaneous melanoma) may also be important in the etiology of acquired benign nevi. PMID- 2321993 TI - Behavior modification obtained by sun protection education coupled with removal of a skin cancer. AB - The 1042 people in this study who had a nonmelanoma skin cancer surgically removed received repetitive and interactive oral and written education in forms of sun protection. One year after these educational efforts, the subjects responded to a questionnaire that measured their compliance. Sixty-two percent complied with starting to use sunscreens and 56% changed their habits of outdoor activities. The portion of behavioral change attributable to surgery alone vs surgery plus education was unable to be determined. Despite intensive educational efforts, the noncompliance was 38%. This study identifies a health risk-taking pattern of behavior among those who were noncompliant. Those over age 65 years tended to be less compliant. When the data were analyzed by the transtheoretical model of behavior change, those already acting on some form of sunscreen use prior to this study achieved 100% compliance with increasing to a sunscreen with a sun protection factor of 15 or greater. It is hoped that with more educational efforts those in precontemplative and contemplative phases of behavior can be recruited to take action, and those who acted by acquiring one sun protective behavior will add other behaviors. PMID- 2321994 TI - The effect of topical tretinoin on dysplastic nevi. A preliminary trial. AB - Twenty-one patients were enrolled in a randomized, double-blind study that examined the effects of topical 0.05% tretinoin (all-trans-retinoic acid; vitamin A acid; Retin-A) solution on dysplastic nevi. Following histologic confirmation of the diagnosis of dysplastic nevus in three representative lesions, patients applied either tretinoin or a placebo containing 50% alcohol to selected dysplastic nevi once a day under tape occlusion, or twice a day unoccluded, for 4 months. Immediate posttreatment comparative photographs showed marked fading or elimination of some dysplastic nevi clinically, and histologic examination of excisional biopsy specimens showed disappearance or reversion to benign nevi in many of the treated lesions. There were no clinical or histologic changes in those dysplastic nevi treated with placebo. This study shows a definite biological effect of topical tretinoin on some dysplastic nevi. PMID- 2321995 TI - Origin of cutaneous melanoma in a congenital dysplastic nevus spilus. AB - Cutaneous melanoma developed in contiguity with a congenital nevus spilus on the leg of a 79-year-old white woman. The unique features of the nevus spilus in this case were its relatively large size (diameter, 8 cm), irregular gross appearance, lifelong stability until the recent appearance of a tumor nodule, and the presence of intraepidermal melanocytic dysplasia appearing as multifocal elements within darkly pigmented speckles distributed throughout a lightly pigmented background of lentigo simplex. Based on this observation, we suggest that the presence of intraepidermal melanocytic dysplasia in nevus spilus may be a predisposing factor for the development of melanoma. The malignant potential of "dysplastic" nevus spilus requires further study. PMID- 2321996 TI - A hypothesis incorporating the histologic characteristics of dysplastic nevi into the normal biological development of melanocytic nevi. AB - A lentiginous pattern of intraepidermal melanocytic hyperplasia, with mild to moderate, random cytologic atypia, forms the conventional basis for the histologic definition of a dysplastic nevus. It is proposed here that these changes actually represent the histologic pattern of a nevus in an active phase of radial growth. The lesser degrees of atypia considered by others to be required for the diagnosis are suggested to overlap changes commonly seen in banal nevi and lentigines. This hypothesis allows the parsimonious concept that a nevus, originating as a lentigo, can at the later sequential junctional, compound, or intradermal stages expand peripherally by a resumption or persistence of the lentiginous pattern of proliferation. The random atypia that is seen in such lesions is suggested to be incidental to the proliferative process rather than indicative of dysplasia as conventionally defined. A familial melanoma-associated phenotype could be accommodated in this model by postulating a heritable defect in mechanisms that control the number or sizes of these hyperplastic lesions. PMID- 2321997 TI - Dysplastic melanocytic nevi. Normal variants or melanoma precursors? PMID- 2321998 TI - The elusive dermatofibromas. PMID- 2321999 TI - Bizarre widespread vesicular eruption. Dermatitis herpetiformis (DH). PMID- 2322000 TI - Asymptomatic erythematous papules in a leukemic patient. Neutrophilic eccrine hidradenitis. PMID- 2322001 TI - Acquired immunodeficiency syndrome and the dermatologist. PMID- 2322002 TI - Pruritic skin eruption in the acquired immunodeficiency syndrome: arthropod bites? PMID- 2322003 TI - Malignant melanoma. PMID- 2322004 TI - Melanosis of the areola. PMID- 2322005 TI - Congenital erosive dermatosis with reticulated supple scarring: first neonatal report. PMID- 2322006 TI - Skin lesions as the sole manifestation of the fetal varicella syndrome. PMID- 2322007 TI - Traditional tattooing of the gingiva: successful treatment with the argon laser. PMID- 2322008 TI - Poikiloderma of civatte. PMID- 2322009 TI - State of leukocyte adhesiveness/aggregation in the peripheral blood of pemphigus and psoriatic patients. AB - The purpose of this study was to assess the role of leukocyte adherence in the pathogenesis of the psoriatic lesion. Use was made of the fact that psoriasis and pemphigus differ considerably as to the presence of leukocytes in the respective lesions: abundance in psoriasis, and absence in pemphigus. The state of leukocyte adhesiveness/aggregation (LAA) was determined in the peripheral blood of 56 patients with psoriasis and 31 patients with pemphigus. Both classes of patients were subdivided into two categories according to the severity of the disease. It was found that in both diseases elevated values of LAA were obtained in the severe cases, whereas the mild cases did not differ significantly from normal controls. Thus, in psoriasis mean LAA values of 9.5% +/- 8% were recorded in the severe patients and 5.5% +/- 4.2% in the mild cases (p = 0.01), while in pemphigus the values were 15% +/- 9.6% and 6.6% +/- 3.7% respectively (p = 0.03). It is concluded that LAA per se does not play a primary role in causing the psoriatic lesion. PMID- 2322010 TI - Stimulation of the recruitment of epidermal Langerhans cells by splenopentin. AB - Splenopentin (SP-5: Arg-Lys-Glu-Val-Tyr), a pentapeptide corresponding to the residues 32-36 of the splenic hormone splenin, increases dose-dependently the number of bone marrow colonies (M and GM colonies). Therefore, we tested the stimulatory effect of SP-5 on the recruitment of epidermal Langerhans cells in skin deprived of these cells. A high dose of cyclophosphamide or dexamethasone led to a drastic decrease of LC density in murine skin with slow and incomplete restoration. SP-5 accelerated Langerhans cell recruitment and led to pretreatment levels of Langerhans cell density in the skin. These results indicate that SP-5 may possibly be used to treat disorders (e.g., HIV infection) where impaired Langerhans cell density and function can lead to secondary cutaneous infections. PMID- 2322011 TI - Cultivation of keratinocytes derived from epidermal explants of sheep skin and the roles of growth factors in the regulation of proliferation. AB - Procedures to promote the growth of primary cultures of keratinocytes derived from sheep epidermis through several passages are described. Rapid epithelial outgrowth was obtained from explants of epidermis isolated from trypsinized inguinal skin biopsy specimens. Following initiation and attachment, cells displayed the polygonal morphology typical of keratinocytes in culture and survived a number of passages before terminally differentiating and sloughing from the surface of the culture vessel. Proliferation occurred in the absence of a feeder layer and was attained in a medium supplemented with foetal bovine serum and hydrocortisone or cholera toxin. Growth was stimulated by the addition of epidermal growth factor or fibroblast growth factor (FGF) to the culture medium. The detection of basic-FGF immunoreactivity in Western immunoblots of extracts of fresh tissues suggests a role for this factor in autocrine or paracrine growth regulation of skin cell populations in vivo. PMID- 2322012 TI - Cyclosporin A administration in dermatology: once a day or in fractional doses? PMID- 2322013 TI - Histological defects of chronic benign familial pemphigus expressed in tissue culture. PMID- 2322015 TI - Arbeitsgemeinschaft Dermatologische Forschung (ADF) in cooperation with Deutsche Dermatologische Gesellschaft. XVII meeting. November 17-19, 1989, Hamburg, Federal Republic of Germany. Abstracts. PMID- 2322014 TI - Histochemical aspects of stratum corneum function in the feline foot pad. PMID- 2322016 TI - The induction of alkoxyresorufin metabolism: a potential indicator of environmental contamination. AB - Methods of biochemical monitoring of individual animals for exposure to environmental contaminants are of great potential use. The hepatic metabolism of various alkoxyresorufins, which are highly specific substrates for certain forms of cytochrome(s) P450, is highly induced by a variety of environmental contaminants. Thus, the O-dealkylation of pentoxy- or benzyloxyresorufin was induced greater than 20-fold in the rat by alpha-hexachlorocyclohexane, 2,4,5,2',4',5'-hexabromobiphenyl, DDT and Aroclor-1254, while the metabolism of ethoxyresorufin was highly induced by 5,6-benzoflavone, 3,4,5,3',4',5' hexabromobiphenyl and Aroclor-1254. Additionally, rats exposed to diets containing as little as 12 ppm DDT displayed greater than five-fold increases in the rate of hepatic O-dealkylation of benzyloxyresorufin. Induction of the hepatic metabolism of these resorufin ethers in 9000 xg supernatant fractions taken from rats exposed to potential environmental contaminants may constitute a valuable diagnostic indicator of the presence of a variety of pollutants, including polycyclic aromatic hydrocarbons, organochlorine pesticides, polyhalogenated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin. These results suggest the potential applicability of these substrates in detecting chemical contamination in the environment. PMID- 2322017 TI - Comparison of cellular and whole-animal bioassays for estimation of radiation effects in the polychaete worm Neanthes arenaceodentata (Polychaeta). AB - The polychaete worm Neanthes arenaceodentata was used in experiments to determine possible relationships between short-term genotoxicity tests and reproductive and lethal consequences of exposure to ionizing radiation. Groups of juvenile N. arenaceodentata received one of four different radiation doses (2, 4, 8, and 16 Gy) to determine dose-effect estimates for chromosomal aberration induction, and groups of both adult and juveniles received one of seven different radiation doses (1, 4, 8.4, 46, 102, 500, and 1000 Gy) to determine dose-effect estimates for reproduction, mortality, and life span. Effects on reproduction and genetic material were observed at the lowest doses and in the same range; detrimental reproductive effects were observed at 1 to 4 Gy, and the frequency of chromosomal aberrations was significantly increased at 2 Gy. Only high doses resulted in acute mortality (greater than 500 Gy) and decreased life span (greater than 100 Gy). Dose-effect estimates for chromosomal aberration induction were dependent on radiation dose and on the stage of the cell cycle at the time of irradiation. Dose-effect estimates for reproduction were dependent on dose and the potential for repopulation of gonadal tissue. It is concluded that short-term genotoxicity test can be predictive of detrimental reproductive effects in those model systems for which basic cell kinetics and reproductive parameters are well known. PMID- 2322018 TI - Characterization of genotoxic components in sediments by mass spectrometric techniques combined with Salmonella/microsome test. AB - The application of Salmonella/microsomal mammalian tests to column chromatography fractions isolated from river and marine sediments collected in the vicinity of Barcelona city, Spain, demonstrated a positive response (TA98 + S9 mix) among the polar fractions. Chemical analysis by high resolution gas chromatography coupled to negative ion chemical ionization mass spectrometry (HRGC-NICI MS) provided sensitivity and selectivity to detect several mutagenic chemical classes. Among them, nitrated PAHs, azaarenes, aromatic amines, anhydrides, and ketones were identified. A total of 116 compounds were tentatively identified, 22 for the first time, of which 16 possessed mutagenic activity. However, a lack of correlation between chemical composition and fraction mutagenicity in the medium polarity fractions, especially in the river sediment, was evidenced. The occurrence of multiple interactions between components in spiked organic extracts is demonstrated. PMID- 2322019 TI - Treatment of acute lead intoxication. A quantitative comparison of a number of chelating agents. AB - The efficacy of several chelating agents in alleviating acute lead intoxication has been investigated in male Swiss mice. The relative effectiveness of diethylenetriaminepentaacetic acid (DTPA), ethyleneglycolbis-(beta-amino ethylether)-N,N'-tetraacetic acid (EGTA), cyclohexanediaminetetraacetic acid (CDTA), L-cysteine, N-acetyl-L-cysteine (NAC), ascorbic acid, sodium diethyldithiocarbamate (DDC), 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3 dimercapto-1-propanesulfonate (DMPS) in reducing lethality of lead was examined. Significant increases in survival were noted with CDTA, ascorbic acid, DMSA, and DMPS. Therapeutic effectiveness (TEF) was determined for these compounds; TEF for ethylenediaminetetraacetic acid (EDTA) and for 2,3-dimercaptopropanol (BAL) was also determined; CDTA (2.33) and EDTA (1.73) showed the highest values. In subsequent experiments, the effect of the chelating agents on the distribution and excretion of lead was investigated. Lead acetate trihydrate was administered subcutaneously at doses of 37.8 mmol/kg (LD50), and fifteen minutes later, chelators were given intraperitoneally at doses approximately equal to one-fourth of their respective LD50 values. EDTA, DTPA and CDTA were the most effective agents in increasing the urinary excretion of lead, whereas DTPA, CDTA, and DDC increased significantly the fecal excretion of lead. EDTA, DDC, and CDTA were the most effective chelators in reducing the concentration of lead found in various tissues. On the basis of these results, CDTA may be considered as an alternative in the treatment of acute lead poisoning. PMID- 2322020 TI - Occupational exposure of grain farmers to carbofuran. AB - Six prairie grain farmers were monitored for pesticide exposure and related adverse effects while they mixed and/or sprayed carbofuran (Furadan 480F) with ground rig application equipment to control grasshoppers in southern Alberta, Canada. Dermal exposure was estimated with Tegaderm patches placed at seventeen locations on the skin beneath the work clothes. Hand and wrist exposure was determined by the amount of chemical found in hand rinses and on wrist patches. Potential inhalation exposure was measured with an air sampler using polyurethane foam as the adsorbent. Urine samples were collected at 24-hr intervals after exposure and monitored for carbofuran. Blood samples were analyzed for acetylcholinesterase (AChE), pseudocholinesterase (ChE) and several other blood parameters. The results indicated that during the mixing and/or spraying operation, a farmer could potentially be exposed to a total of 1,264 micrograms carbofuran per kg of active ingredient (a.i.) used. Of this amount, 1,262 micrograms/kg (or 99.8%) was dermal and 2 micrograms/kg (or 0.2%) could be through the inhalation route. Hand and wrist exposure was about 1,100 micrograms/kg a.i. (or 87% of total exposure). Excretion of the chemical in the urine amounted to 28 micrograms/kg a.i. No ChE inhibition was observed. Other blood measurements were within normal ranges. The farmers showed no acute adverse effects during exposure and for four days after exposure. These results are discussed in relation to the mammalian toxicity of carbofuran. PMID- 2322021 TI - The effects of pesticides on some biochemical parameters of carp (Cyprinus carpio L.). AB - Treatments with copper sulphate (CuSO4), paraquat (PQ) and methidathion (MD) caused tissue damage and stress effects in carp, indicated by the increased lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), and glutamate dehydrogenase (GIDH) enzyme activities and elevated blood-sugar levels. Copper sulphate, administered together with PQ and MD, were synergistic in terms of tissue damage and stress effects. The isoenzyme patterns showed organ-specific tissue damage. The administered chemical and isoenzymes indicating liver damage were detectable in the blood. The combination of CuSO4 and MD caused focal cell necrosis, which was observable in the liver tissue by light microscopy. Electron microscopic studies revealed the presence of damaged parenchymal cells with electron transparent cytoplasms, myelin figures, and altered mitochondria ER and Golgi. PMID- 2322022 TI - Chlorinated pesticides in foodstuffs in Hong Kong. AB - The movement of pesticides into and out of Hong Kong shows a high net gain of DDT and benzene hexachloride (BHC). 310 food samples were analyzed for total BHC and 1,854 food samples were analyzed for total DDT, total DDE, and total TDE. High levels of total BHC and total DDT were found in foodstuffs in Hong Kong. Estimated daily ingestion of total BHC and total DDT were 10 and 9 times higher than that found in the United States of America. These results correlate with the known high body accumulations of beta BHC and p,p' DDT as shown in high pesticides levels of local human breast milk. Certain foodstuffs, such as preserved fruits, preserved eggs, salted fish and pond fish, had very high levels of pesticides. Sources of contamination and existing government legislations are discussed and recommendations made. PMID- 2322023 TI - Association between HLA-DR antigens and rheumatoid arthritis in Arabs. AB - Eighty five Arab patients with classical and definite rheumatoid arthritis were typed to determine the prevalence of HLA A, B, C, and DR antigens. A significant increase in the prevalence of HLA-A10, B8, B21, and DR3 was found in comparison with a control population matched for age and sex. HLA-DR5 was significantly decreased in the patient group. The classical association of HLA-DR4 with rheumatoid arthritis could not be confirmed in the Arab patients resident in Kuwait, supporting reported observations in different ethnic groups of associations with HLA antigens other than HLA-DR4 and indicating a heterogeneous genetic susceptibility to rheumatoid arthritis. PMID- 2322024 TI - Qualitative and quantitative expression of VHI associated cross reactive idiotopes within IgM rheumatoid factor from patients with early synovitis. AB - Monoclonal rheumatoid factors (RFs) of the major Wa cross reactive idiotype group have been shown to express exclusively VKIII subgroup light chains and VHI subgroup heavy chains. A VKIII associated cross reactive idiotope (CRI) (17-109), however, was shown not to be exclusively expressed on IgM paraproteins having rheumatoid factor activity or to be present at increased levels in the sera of patients with rheumatoid arthritis (RA). Three VHI associated CRIs have been defined with monoclonal antibodies and quantitative studies of their representation are reported, together with VKIII, in IgM and IgM RF isolated from the sera of patients with early synovitis, some of whom progressed to classical RA. The results show (a) the probed CRIs were expressed predominantly on IgM RF rather than on non-RF IgM; (b) 5-10% of IgM RFs from patients with classical RA expressed the CRIs, but this represented a lower proportion of IgM RFs than observed for normal individuals or patients with self limiting synovitis; (c) VKIII light chains were highly associated with IgM RFs rather than non-RF IgM (75% and 25% respectively). It is suggested that the CRIs probed are markers for germline gene encoded antibodies or sequences resulting from minimal mutation of germline genes. The lowered proportion of RFs expressing CRIs in RA may therefore be evidence of polyclonal activation or specific antigenic stimulation, or both, resulting in maturation of the RF response with recruitment of further VH genes or extensive mutation of germline genes. These studies show that monoclonal RFs are relevant models of RF produced in RA and that the repertoire of RF autoantibodies may be encompassed within a small number of CRI expressing families. PMID- 2322025 TI - Rarity of synovitis in polymyalgia rheumatica. AB - The joints of 56 patients with polymyalgia rheumatica were examined for evidence of inflammatory synovitis. x Rays, isotope scans, and thermography supplemented clinical examination. Control sternoclavicular joints were examined at necropsy. Peripheral and axial synovitis were uncommon and the results contrast with the findings of several recent studies. PMID- 2322026 TI - Effect of weather conditions on rheumatic patients. AB - In a one month prospective study of 62 rheumatic patients--16 with rheumatoid arthritis (RA), 24 with osteoarthritis (OA), 11 with inflammatory arthritis, 11 with fibromyalgia joint pain--swelling and everyday activity was compared with changes in daily weather conditions. In most patients weather changes increased arthritic symptoms. Women were more sensitive to weather than men (62% v 37%). Pain was affected positively by barometric pressure and temperature in RA, by temperature, rain, and barometric pressure in OA, and by barometric pressure in fibromyalgia. These results support the belief of most rheumatic patients that weather conditions significantly influence their day to day symptoms. PMID- 2322027 TI - Autoantibody and idiotype profile of lung involvement in autoimmune rheumatic disease. AB - Several reports have linked the presence of certain serum autoantibodies with particular clinical manifestations of autoimmune disease. For example, the Jo-1 antibody is now established as a marker for fibrosing alveolitis in polymyositis. To investigate the possible association of further autoantibodies or idiotypes with fibrosing alveolitis in autoimmune rheumatic disease a panel of autoantibodies was measured in serum samples from 28 patients with systemic lupus erythematosus (SLE) (10 with and 18 without lung involvement), 21 patients with scleroderma (12 with fibrosing alveolitis and nine without), and 41 patients with 'lone' fibrosing alveolitis. Antibodies measured were IgM and IgG anti-dsDNA and anti-ssDNA antibody; IgG and IgM anticardiolipin antibody; anti-poly (ADP-ribose) antibody; antibodies to two common idiotypes of anti-DNA antibodies, designated 134 and 16/6; and IgM, IgG, and IgA isotypes of rheumatoid factor. None of these antibodies was specifically associated with lung involvement in SLE or scleroderma, but a trend was found towards an increase in all autoantibodies in association with lung disease in SLE, while the reverse trend was seen in scleroderma. PMID- 2322028 TI - Systemic lupus erythematosus presenting as pneumococcal septicaemia and septic arthritis. AB - A 50 year old woman presented with pneumococcal septicaemia, septic arthritis, and a lobar pneumonia and was subsequently diagnosed as having systemic lupus erythematosus. The blood film and splenic 99mTc sulphur colloid uptake were normal, although selective functional hyposplenism was shown by the impaired clearance of immunoglobulin coated erythrocytes. Systemic lupus erythematosus presenting with fulminating pneumococcal sepsis in the presence of selective defects in spleen function is previously unreported. PMID- 2322029 TI - Infective arthritis due to Blastocystis hominis. AB - A patient with rheumatoid arthritis taking prednisone developed Blastocystis hominis acute diarrhoea, which was associated with increased inflammation and effusion of the left knee. B hominis organisms were found in synovial fluid from the left knee. The patient responded dramatically to metronidazole treatment. B hominis may become disseminated in immunosuppressed patients with diarrhoea and may cause infective arthritis. PMID- 2322030 TI - Assessment of rheumatoid arthritis. PMID- 2322031 TI - Methotrexate treatment of Felty's syndrome. PMID- 2322032 TI - Giant cell arteritis presenting as a supraclavicular nodule. PMID- 2322033 TI - Pyridoxylated hemoglobin solution as an oxygen carrier. PMID- 2322034 TI - The efficacy of polymerized pyridoxylated hemoglobin solution as an O2 carrier. AB - A polymerized pyridoxylated hemoglobin solution (Poly SFH-P) has been prepared with a normal [Hb] of 14 g/dL, a normal COP of 20 to 25 torr, a P50 of 16 to 20 torr, and a plasma T1/2 of 40 to 46 hours. Animals underwent a total exchange transfusion with Poly SFH-P to assess its ability to support hemodynamics and oxygen transport in the absence of red cells. All animals survived the exchange transfusion. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and oxygen consumption (VO2) remained at baseline values at zero hematocrit after the exchange. The final plasma [Hb] at Hct less than 1% was 9.7 +/- 0.4 g/dL. These results are significantly better than previous data with unmodified tetrameric hemoglobin solution (SFH). Poly SFH-P supports life in the absence of red cells. In contrast to SFH, Poly SFH-P achieves a nearly normal [Hb], a longer T1/2, and maintains baseline hemodynamics and oxygen consumption at zero hematocrit. These results document that Poly SFH-P is an effective oxygen carrier that offers greater potential than previous products as a clinically useful red cell substitute. PMID- 2322035 TI - The cause of dysphagia in uncomplicated sliding hiatal hernia and its relief by hiatal herniorrhaphy. A roentgenographic, manometric, and clinical study. AB - Patients with an uncomplicated sliding hiatal hernia frequently experience dysphagia. The present study shows, using video barium contrast esophagograms, that the cause of dysphagia in 60% of these patients is an obstruction to the passage of the swallowed bolus by diaphragmatic impingement on the herniated stomach. Manometrically this was reflected by a double-hump high pressure zone (HPZ) at the gastroesophageal junction, and specifically to the length and amplitude of the distal HPZ and the length of the intervening segment between the two HPZs. The former represents the degree of the diaphragmatic impingement on the herniated stomach and the latter the size of the supradiaphragmatic herniated stomach. Surgical reduction of the hernia resulted in relief of dysphagia in 91% of the patients. PMID- 2322036 TI - Bleeding duodenal ulcer. A prospective evaluation of risk factors for rebleeding and death. AB - There were 12 hospital deaths in 433 patients (2.8%, 1.6% at 30 days) presenting with bleeding duodenal ulcer. Excluding patients who underwent immediate operation or early elective surgery, where ulcer size was measured at initial endoscopy rebleeding was evident in 40/288 patients (13.9%) and was associated with an increased mortality (0.4% v 12.5%) (p less than 0.0001). Rebleeding rates for ulcers less than or equal to 1 cm and greater than 1 cm were respectively 28/239 (11.7%) and 12/49 (24.5%) (p less than 0.02). Rebleeding occurred in 13/186 patients (7.0%) in whom endoscopic stigmata of recent haemorrhage were absent and in 27/102 (26.5%) with such stigmata (p less than 0.0001). The mortality rate for patients without stigmata was 3/186 (1.6%) whilst mortality figures for patients with ulcers less than or equal to 1 cm and greater than 1 cm in size were respectively 0/77 and 3/25 (12.0%) when stigmata were identified. Ulcers greater than 1 cm were more frequent in the greater than 60 year age group, more likely to have stigmata and carried an increased risk of rebleeding and mortality. PMID- 2322037 TI - Effects of percutaneous transhepatic biliary drainage on blood-bile permeability and selective IgA transport in patients with biliary obstructions. AB - Biliary obstruction induces a increase in the permeability between blood and bile, and a decrease in the rate of immunoglobulin A (IgA) transport into bile. We investigated the effects of percutaneous transhepatic biliary drainage (PTBD) on these derangements. PTBD reduced the extent of elevation of the bile-to-serum ratio of Immunoglobulin G (IgG; IgG-BS ratio) in patients with obstructive jaundice. Because IgG is known to be passively transported from serum to bile, the results indicate that PTBD restores the blood-bile barrier function. The IgA BS ratio/IgG-BS ratio index (IgA/IgG index) and the IgM/IgG index, which indicated the function of selective transport of IgA and IgM into bile, initially decreased and then returned to the normal range 17 days after PTBD in patients who experienced a rapid resolution of hyperbilirubinemia. However these indices remained low in patients who did not experience this resolution. The serum secretory IgA levels in patients who did not experienced rapid resolution of hyperbilirubinemia markedly increased before PTBD. The serum secretory IgA levels in the patients who did and those who did not experience rapid resolution of hyperbilirubinemia, after initially increasing, decreased after PTBD. However the level returned to the control range only in patients who experienced a rapid resolution. These results indicate that the secretory IgA level is a sensitive indicator of hepatobiliary function, and measurement of the level of secretory IgA could predict the effect of PTBD. PMID- 2322038 TI - The increasing prevalence of acalculous cholecystitis in outpatients. Results of a 7-year study. AB - Acute acalculous cholecystitis (AAC) is a disease that causes high rates of morbidity such as those traditionally observed in the critically ill. Recently we noted an increase in the de novo presentation of outpatients with this disease. Our aim was to characterize this disease in outpatients, identify risk factors, and assess clinical outcome. Therefore a 7-year review of the Yale experience with AAC was undertaken. Forty-seven patients were identified. Seventy-seven per cent (36 of 47 patients) developed AAC at home without evidence of acute illness or trauma, while 23% (11 of 47 patients) developed the disease while hospitalized. Significant vascular disease was observed in 72% of outpatients. A 38% morbidity rate and 6% mortality rate were observed. We conclude that AAC occurs commonly in elderly male outpatients with vascular disease and that these patients incur significant morbidity in association with this condition. AAC should be suspected and prompt surgical management instituted when these patients present with an acute right upper quadrant inflammatory process. PMID- 2322040 TI - A prospective study on fish bone ingestion. Experience of 358 patients. AB - A prospective study was performed on 358 patients to examine the diagnosis, management, and natural history of fish bone ingestion. All patients admitted with the complaint had a thorough oral examination. Flexible endoscopy under local pharyngeal anesthesia would be performed on patients with negative findings. Of 117 fish bones encountered, 103 were removed (direct removal, 21; endoscopic removal, 82) and 12 were inadvertently dislodged. One was missed and the other one necessitated removal with rigid laryngoesophagoscopy under general anesthesia. Morbidity (1%) occurred in patients with triangular bones in the hypopharynx, resulting in one mucosal tear and two lengthy procedures. Mean hospital stay was 7 hours. Prediction of the presence of fish bones by symptoms and radiograph was poor. The location of symptoms, however, was useful in guiding the endoscopist to the site of lodgment. Of patients who refused endoscopy, only one (2.8%) developed retropharyngeal abscess. As compared to those who received endoscopy, 31.8% had fish bones detected. As the yield of fish bone detected was also inversely related to the duration of symptoms, we strongly suspect that most of the unremoved fish bones would be dislodged and passed. However, because of the serious potential complication from fish bone ingestion, we believe that a combination of oral examination followed by flexible endoscopy is indicated in all patients. When triangular bones in the hypopharynx are encountered, rigid laryngoesophagoscopy should be considered. This protocol had safely and effectively dealt with the present series of patients. PMID- 2322039 TI - Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. AB - Twenty-one years ago, Howard published a paper entitled "Forty-one Consecutive Whipple Resections Without an Operative Mortality." That paper stimulated the present analysis of the last 118 consecutive pancreatoduodenectomies (107 Whipple and 11 total resections) performed at the Surgical University Clinic Mannheim from November 1985 to the present day with no deaths. Ninety-one resections were performed for neoplasms and 27 were for complicated chronic pancreatitis. The preoperative evaluation, operative technique, and postoperative care of these cases is discussed in detail and compared to the experience of Howard. While there was general agreement on operative technique, there were differences concerning preoperative evaluation (modern imaging methods) and postoperative care (simplification). In this series 21 postoperative complications required seven relaparotomies. Long-term survival after resection for carcinoma was analyzed for 133 consecutive patients who were shown to have true ductal adenocarcinoma. In 76 patients, who had radical (R0-) resections, the actuarial 5 year-survival rate was 36%. In 44 patients, whose R0-resections for pancreatic cancer occurred more than 5 years ago, the actual survival rate was 25%. PMID- 2322042 TI - Who, hobbies, and heroes. PMID- 2322041 TI - Wound infection rates after invasive procedures in HIV-1 seropositive versus HIV 1 seronegative hemophiliacs. AB - One-hundred and two patients with hemophilia A, hemophilia B, or acquired antibody to factor VIII who had undergone invasive procedures were cross referenced with patients participating in an ongoing prospective natural history study of HIV-1 infection in hemophiliacs. Matching revealed that HIV-1 status was known for 83 patients (83%) who had undergone 169 procedures between July 1979 and April 1988. Invasive procedures were classified as clean in 108 patients (63.9%), clean-contaminated in 45 (26.6%), contaminated in 2 (1.2%), and infected in 14 (8.3%). Wound infection rates by HIV-1 status were as follows (95% confidence intervals): HIV+ 1.4% (0% to 5%), HIV- 0% (0% to 9%), and procedure before testing HIV+ 1.5% (0% to 6%). There were no significant differences between the wound infection rates of HIV-positive and HIV-negative hemophiliacs nor in the wound infection rate among all three subgroups of patients (p greater than 0.5, Fisher's Exact Test). We conclude that surgery in HIV-1-infected patients who have not progressed to AIDS does not entail an increased risk of postoperative wound infections. PMID- 2322043 TI - Assessment of spinal cord blood supply during aortic operations. PMID- 2322044 TI - Controversies about Barrett's esophagus. PMID- 2322045 TI - Myocardial energetics and the postischemic heart. PMID- 2322046 TI - Preliminary report of localization of spinal cord blood supply by hydrogen during aortic operations. AB - One source of paraplegia after aortic operations is the failure to reattach the spinal cord blood supply, the origins of which are not evident at operation. This report is concerned with a rapid new method of identifying these vessels intraoperatively. In 9 pigs, a specially designed catheter with platinum and stainless steel electrodes was inserted intrathecally. Saline solution saturated with hydrogen was injected sequentially into arterial ostia at T-15 to L-4 inclusive, and the generated current impulses from the conditioned platinum electrode were recorded. Of 90 potential segmental arteries supplying the spinal cord, 28 gave rise to spinal radicular arteries. Hydrogen-induced current impulses correctly located 25 of the radicular arteries and all those larger than 180 microns in diameter. When injected with indigo carmine, the vessels localized by the hydrogen-induced current impulses filled the entire anterior spinal artery from the low thoracic to the sacral region, whereas injection of the other vessels did not show filling. After refinement and testing for safety, this method has been employed clinically to rapidly localize and reattach routes of critical cord circulation. PMID- 2322047 TI - Effect of antireflux operation on Barrett's mucosa. AB - Regression of Barrett's epithelium after antireflux operations remains a controversial topic. We evaluated the effect of antireflux procedures in patients with Barrett's esophagus on the regression of columnar epithelium and dysplasia and its potential protective effect on the subsequent development of carcinoma. Of the 241 patients with Barrett's esophagus treated at the Lahey Clinic from 1973 to 1989, 37 patients underwent an antireflux operation. Regression was defined as histological evidence of regenerating squamous mucosa that completely or partially replaced the columnar epithelium. Improvement in lower esophageal sphincter pressure to 12 mm Hg or greater occurred in 19 of 26 patients (73%) who had perioperative manometry. Symptomatic relief of esophagitis occurred in 34 of 37 patients (92%). Four patients had partial regression with regenerating squamous mucosa juxtaposed with areas of columnar epithelium. Carcinoma developed in 3 of 37 patients (8.1%). One patient had recurrence of severe symptoms of reflux esophagitis before development of carcinoma. Patients with Barrett's esophagus who have undergone a successful antireflux operation with symptomatic relief and evidence of improvement in lower esophageal sphincter pressures rarely show regression of Barrett's mucosa and may still be at risk for development of carcinoma. Therefore, the indications for antireflux operation in Barrett's esophagus should remain the same as for other patients with gastroesophageal reflux, but yearly endoscopic and histological surveillance should be continued postoperatively. PMID- 2322048 TI - Relationship between total mechanical energy and oxygen consumption in the stunned myocardium. AB - We studied the relationship between left ventricular oxygen consumption (LVVO2) and total ventricular mechanical energy production as determined by calculation of the systolic pressure-volume area (P-VA) before and after 25 minutes of warm ischemia in 7 sheep. We compared the relationship between LVVO2 and P-VA with the relationships between LVVO2 and stroke work and between LVVO2 and the systolic stress integral. Using the methods presented, P-VA can be measured in vivo (n = 123) in both preischemic and postischemic hearts. Ischemia increases the slopes of the relationship between LVVO2 and P-VA and between stroke work and the systolic stress integral, and reduces the oxygen utilization efficiency of stroke work to less than 2%. Coefficients of determination for the relationship between LVVO2 and P-VA are, in general, higher than those between LVVO2 and either stroke work or the systolic stress integral. We conclude that systolic P-VA can be measured in vivo using recently developed methods and that it is applicable to postischemic "stunned" hearts. Because P-VA and LVVO2 can be converted into identical energy units, calculation of P-VA permits calculation of myocardial oxygen utilization efficiency. PMID- 2322049 TI - Reoperation for thymoma: report of 23 cases. AB - Twenty-three patients underwent reoperation for thymoma at intervals of 2 months to 17 years 10 months after the initial operation. There were no operative or hospital deaths. Myasthenia gravis occurred in 12 patients, but in only 2 was it a determinant for reoperation. The longest survival after reoperation is 12 years 9 months, and that patient is free from tumor. Four distinct surgical groups emerged, and their recognition provides an improved method of reporting and suggests a strategy for better overall management. Group 1 (n = 5) had completion of thymectomy (reoperation) after thymomectomy alone or after incomplete thymectomy. The interval was 2 months to 17 years 10 months. All 5 had myasthenia gravis. At reoperation, thymomas were found in 3 and a hyperplastic thymus in 2. Four are alive and tumor free 2 years to 8 years 2 months after reoperation. One died tumor free after 5 years. Group 2 (n = 8) had reoperation for recurrent thymoma after standard (presumably complete) resection. The interval was 2 years to 13 1/2 years. Four had myasthenia gravis. Four are alive 8 months to 5 years 8 months after reoperation, 3 without detectable tumor. Four died 3 years 3 months to 8 years 4 months after reoperation, 3 free from tumor. Group 3 (n = 8) underwent reoperation for initially unresectable thymoma after adjuvant treatment with chemotherapy, radiotherapy, or both. The interval was 3 months to 4 years 8 months. Three had myasthenia gravis. Six are alive 4 months to 4 years after reoperation, only 1 with tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322050 TI - Retrograde coronary sinus cardioplegia for aortic valve operations: a clinical report on 500 patients. AB - Retrograde delivery of cardioplegic solutions has recently been the subject of renewed interest, but the reliability of this technique has not been assessed in large clinical series. From 1980 to 1989, we used retrograde coronary sinus perfusion as the exclusive means of cardioplegia delivery in 500 consecutive patients undergoing aortic valve replacement, either isolated (359 patients) or combined with another valve or coronary procedure (141 patients). The coronary sinus was always cannulated under direct vision after bicaval cannulation with snaring. Cold crystalloid cardioplegia was delivered retrogradely at an average flow rate of 100 mL/min in conjunction with topical and systemic (25 degrees C) hypothermia. The mean cross-clamp time was 83 +/- 23 minutes (+/- the standard deviation). There were 31 hospital deaths (6.2%), 20 of which were cardiac related. Transient hemodynamic instability (defined as a need for inotropic agents for less than 24 hours postoperatively) occurred in 16 patients (3.2%), whereas a true low-output syndrome developed in 60 patients (12%). The incidence of clinically significant supraventricular arrhythmias and of permanent conduction defects was 7.4% and 1.2%, respectively. There were three nonfatal coronary venous injuries during our early experience. We conclude that coronary sinus perfusion is a safe and effective means of delivering cardioplegia in aortic valve operations. While providing a degree of myocardial protection similar to that reported with anterograde cardioplegia, the coronary sinus technique offers distinct advantages, in particular, the avoidance of perfusion related coronary artery complications and the opportunity to repeat cardioplegia administration without interrupting the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322051 TI - Skeletonization of the atrioventricular node for AV node reentrant tachycardia: experience with 32 patients. AB - We describe our experience with operative therapy for atrioventricular (AV) node tachycardia using an anatomically guided procedure. The operative rationale was to dissect the AV node from most of its atrial inputs (AV node "skeletonization") with the intent of altering the perinodal substrate and preventing reentry. The anteroseptal and posteroseptal regions were initially approached epicardially to facilitate identification of anatomical structures. Under normothermic cardiopulmonary bypass, the right atrial septum was mobilized and the intermediate AV node was exposed anterior to the tendon of Todaro. Atrioventricular node conduction was monitored electrocardiographically throughout the procedure. Ablation of concomitant accessory pathways was done prior to AV node skeletonization. Thirty-two patients aged 9 to 67 years (mean age, 30 years) underwent operation. Five patients had concomitant accessory pathways in addition to AV node reentry. At electrophysiological study before discharge, no patient had AV block although anterograde and retrograde Wenckebach cycle lengths were significantly prolonged. Six patients had retrograde AV block. Twenty-nine patients are free from arrhythmia and require no antiarrhythmic medication after a follow-up of 1 month to 45 months (mean follow-up, 17 months). Three patients had recurrence of tachycardia ten days, 2 months, and 7 months postoperatively. All patients subsequently had a successful reoperation. PMID- 2322052 TI - Effect of omental, intercostal, and internal mammary artery pedicle wraps on bronchial healing. AB - Bronchial transection and devascularization is necessary in the course of sleeve resection or lung transplantation, leaving distal bronchial segments ischemic and subject to stricture or dehiscence. Thirty mongrel dogs underwent left lung autotransplantation. The bronchial anastomosis was wrapped with omentum (n = 9), intercostal muscle pedicle (n = 9), or internal mammary artery pedicle grafts (n = 6). Six control animals underwent bronchial anastomosis without an external wrap. Bronchial revascularization by capillary ingrowth from the pedicle to the bronchial submucosal plexus was demonstrated with all three types of vascular pedicle grafts; however, more consistent and confluent vascular ingrowth was provided by internal mammary artery pedicle grafts. Additionally, the bronchial anastomotic cross-sectional area was significantly better in the internal mammary artery group (84.5 +/- 3.3) as compared with that of the omental (68.4 +/- 8.3), intercostal muscle (66.9 +/- 10.9), or control groups (70.2 +/- 7.6). An internal mammary artery pedicle graft and the presence of dense confluent submucosal vascular ingrowth from any pedicle graft were independently predictive (p less than 0.05) of minimizing bronchial anastomotic narrowing. These data are consistent with previous findings suggesting that omental and intercostal muscle pedicle grafts promote early bronchial revascularization; moreover, the data demonstrate the superiority of an internal mammary artery pedicle graft to provide submucosal vascular ingrowth and to minimize anastomotic stenosis. PMID- 2322053 TI - Thoracic aortic aneurysms after acute type A aortic dissection: necessity for follow-up. AB - Between April 1979 and May 1989, 86 patients underwent emergency operation for acute type A aortic dissection. Sixty-four (74.4%) survived. None of the survivors died of late aortic complications. Fifty-eight patients were followed 3 months to 10 years (mean follow-up, 3.2 years) postoperatively with computed tomography and digital subtraction angiography. Dilatation of the distal aorta (diameter size range, 6 to 10.5 cm) developed in 10 patients (17%). Six patients underwent replacement of the descending aorta 1 month to 21 months (mean period, 8.5 months) after aortic dissection repair. Two of them had third-stage thoracoabdominal replacement. In 2 patients, replacement of the descending aorta was scheduled; 1 died before reoperation and 1 refused the procedure. Two patients underwent aortic arch replacement; it is scheduled for another (fourth stage). There were no deaths among the patients having reoperation. The rate of indications for reoperation on the aorta downstream from the original repair 1 month to 6 years 4 months (median time, 9 months) after primary surgical intervention for acute type A aortic dissection was 24% (14 reoperations in 10 of 58 patients). This study underscores the importance of close follow-up of patients having operation for acute type A aortic dissection. Early recognition of progressive downstream aortic pathology permits effective prevention of aortic rupture and timely reoperation. PMID- 2322054 TI - Effects of intraoperative plasmapheresis on blood loss in cardiac surgery. AB - Intraoperative platelet-rich plasmapheresis allows autotransfusion of fresh, undamaged platelets and clotting factors at the completion of the operation. To evaluate this technology, we randomly assigned 100 consecutive patients who were to undergo an elective coronary bypass procedure and had normal clotting studies into the experimental (plasmapheresis) or the control group. Characteristics of both groups were similar, including average age (61.4 years versus 61.3 years [experimental versus control group]), sex (78% male versus 74% male), preoperative weight (80.9 kg versus 80.2 kg), preoperative red cell mass (1,989 mL versus 1,890 mL), perfusion time (102 minutes versus 106 minutes), and coagulation studies. Both internal mammary arteries were used in 68% of the patients. All patients had preoperative and postoperative blood volume determinations and complete clotting studies. Sixty-two variables related to bleeding were analyzed. Strict indications for transfusion were a hemoglobin level less than 7 g/100 mL in patients younger than 70 years and a hemoglobin level less than 8 g/100 mL in patients older than 70 years. The group receiving intraoperative plasmapheresis had a significant reduction in operative red cell mass loss (1,050 +/- 43 mL versus 1,226 +/- 61 mL; p = 0.021), a reduction in the average homologous transfusion (0.67 +/- 0.15 unit versus 1.8 +/- 0.25 units; p = 0.0002), and an increase in the percentage of patients not requiring blood transfusions (66% versus 32%; p = 0.001). This technique is useful in reducing postoperative blood loss and homologous transfusions. PMID- 2322055 TI - Surgery for high cervical esophageal carcinoma: experience with 11 patients. AB - The treatment of carcinoma of the cervical esophagus remains controversial. Eleven patients with carcinoma of the high cervical esophagus were encountered over the past 7 years at our institution. There were 6 men and 5 women whose ages ranged from 51 to 72 years. Six patients had tracheal or laryngeal invasion. In all instances one-stage pharyngolaryngoesophagectomy with pharyngogastric (6 patients) or pharyngocolic (5 patients) reconstruction was performed. There was one hospital death. Six patients died 6 to 35 months postoperatively: 1 from recurrence, 2 from generalized metastases, and 3 with both local recurrent and metastatic disease. One other patient died free of disease 6 weeks postoperatively of pneumonia. The remaining 3 patients are alive 12 to 84 months after operation with excellent rehabilitation and good quality of life. We conclude that one-stage surgical resection and reconstruction for high cervical carcinoma of the esophagus offers good palliation and possible long-term survival with acceptable operative risk. PMID- 2322056 TI - True emergency coronary artery bypass surgery. AB - Previous reports of emergency coronary artery bypass grafting often included cases that were not true surgical emergencies, thereby creating inappropriately favorable results. To accurately investigate this important subgroup of patients, we analyzed our recent experience with truly emergent coronary artery bypass grafting. From January 1984 to January 1989, 117 patients underwent true emergency bypass grafting for acute refractory coronary artery ischemia. Clinical deterioration was associated with failure of percutaneous angioplasty in 37 patients and instability during diagnostic catheterization in 13 patients. Refractory ischemia developed in the remaining patients while on the ward or in the intensive care unit. All operations were performed within four hours of surgical consultation, most within one hour. Overall in-hospital operative mortality was 14.5% (17/117), and 76.5% of deaths (13/17) were due to cardiac related causes. Major morbidity occurred in 35.9% (42/117). Univariate analysis isolated ejection fraction, extent of coronary artery disease, previous myocardial infarction, hypertension, need for inotropic support, use of an intraaortic balloon pump, and cardiopulmonary resuscitation as risk factors for operative mortality. Stepwise multivariate analysis confirmed that previous myocardial infarction, hypertension, cardiopulmonary resuscitation, and reoperation were independently significant risk factors. Age, sex, diabetes, left main disease, and peripheral vascular disease had no significant impact on the prognosis. The 4% operative mortality (2/50) for patients taken directly to the operating room from the catheterization suite was significantly lower than the 22.4% mortality (15/67) associated with emergencies arising on the ward or intensive care unit (p less than 0.01). A logistic risk equation developed from this population accurately modeled operative mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322057 TI - Surgical treatment of cardiac tumors: a 25-year experience. AB - From 1964 to 1989, we performed operations on 133 patients with cardiac tumors. There were 58 male and 75 female patients ranging in age from three days to 81 years; 101 were adults, and 32 were children (less than 12 years of age). Primary tumors (102 benign and 12 malignant) were found in 114 patients and metastatic tumors in 19. Symptoms included congestive heart failure, arrhythmias, emboli, and chest pain. Diagnosis was accomplished through angiography, echocardiography, computed tomography, and magnetic resonance imaging. Operative treatment encompassed techniques ranging from biopsy to complete excision (including hypothermic circulatory arrest and cardiac autotransplantation) depending on the site of disease and the extent of involvement. Overall operative survival was 91%. Twelve patients died early (within 30 days of operation), and follow-up was obtained for 110 (90.9%) of the remaining 121 survivors (total patient-years of follow-up, 572.8; mean follow-up, 5.2 years). Of the 20 patients who died late, 15 had malignant disease. Operative survival for patients with primary cardiac malignancies and for those with metastatic disease was 83% and 68.4%, respectively, with 3 and 5 patients, respectively, still living. We advocate an aggressive surgical approach, especially in patients with benign tumors, who can expect an excellent outcome. For patients with malignant or metastatic disease, palliation and cure are also possible if aggressive surgical actions are taken. PMID- 2322058 TI - Results of homograft aortic valve replacement for active endocarditis. AB - Since July 1985, cryopreserved homograft prostheses have been used for aortic valve replacement in 10 patients, aged 2 to 77 years, with active endocarditis. Five patients had positive bacterial cultures from excised valves, and all had clinical findings of uncontrolled infection while receiving appropriate antibiotics. Homograft valves (four) or valved conduits (six) were implanted for treatment of sepsis (6 patients), congestive heart failure (3) or recurrent emboli (1 patient), and complicating native (5 patients) or prosthetic valve (5) endocarditis. Staphylococci (6 patients), streptococci (3), and Candida (1) were infecting organisms. Preoperatively, Doppler echocardiography showed aortic regurgitation in all patients. At operation, 9 patients had gross vegetations, 9 had single or multiple abscess cavities, and 5 had pericarditis. Complex reconstruction of the aortic valve and annulus with homograft conduits was necessary in 6 patients (3 with previous aortoventriculoplasty). Two early deaths (ventricular failure, perioperative stroke) occurred. Mean follow-up of all operative survivors was 2.1 years (range, 0.6 to 3.6 years), and one late death resulted from arrhythmia. Homograft valve regurgitation increased in 1 patient, and 7 late survivors are asymptomatic. No patient has had recurrence of endocarditis. We conclude that cryopreserved homograft aortic valve/root replacement is an effective method for management of active endocarditis complicated by annular destruction. PMID- 2322059 TI - Controlled initial hyperkalemic reperfusion after cardiac transplantation: coronary vascular resistance and blood flow. AB - The coronary vascular response to controlled initial hyperkalemic reperfusion after global ischemia during cardiac transplantation was studied in 11 patients. The mean global ischemic time was 206 minutes (range, 143 to 245 minutes). All donor hearts received initial hyperkalemic crystalloid cardioplegia and subsequent oxygenated crystalloid cardioplegia during implantation. Coronary blood flow was highest during the first one to two minutes of controlled reperfusion but remained normal throughout the first ten minutes of reperfusion. Coronary vascular resistance was less than normal throughout the first ten minutes of controlled reperfusion, but there was a gradual increase throughout this period. Systemic vascular resistance remained within normal limits. The time to effective contraction was highly variable, but a greater potassium load during initial reperfusion was generally associated with a longer time to effective contraction. PMID- 2322060 TI - Ascending aortic dissection in weight lifters with cystic medial degeneration. AB - We report 4 cases of ascending aortic dissection in patients with long histories of weight lifting. In 2 of the patients, the initial symptoms of dissection developed while they were lifting weights. Two patients had a history of hypertension and 2 had previously used anabolic steroids. All 4 were successfully treated surgically. Histopathology showed aortic medial changes in all 4. We believe that the hemodynamic stresses of weight lifting, namely, a rapid increase in systemic arterial blood pressure without a decrease in total peripheral vascular resistance, in combination with aortic medial degeneration may have contributed to the development of the aortic dissection. PMID- 2322061 TI - Determinants of survival and valve failure after mitral valve replacement. AB - A prospective evaluation of 333 consecutive patients undergoing isolated mitral valve replacement between 1982 and 1985 was performed to identify the predictors of survival and valve failure. Follow-up between 2 and 6 years postoperatively (mean, 32 +/- 17 months) was 98% complete. Four prostheses were inserted to permit a prospective evaluation of alternative valves: Bjork-Shiley mechanical (n = 118), Ionescu-Shiley pericardial (n = 146), Carpentier-Edwards porcine (n = 38), and Hancock pericardial (n = 31). Hospital mortality was 6%, and actuarial survival at 5 years was 74% +/- 5%. Multivariate Cox regression analysis identified advancing age (less than 40 years, 88% +/- 7%; greater than 70 years, 50% +/- 14%) and poor left ventricular function (ejection fraction less than 0.20, 62% +/- 17%; ejection fraction greater than 0.60, 80% +/- 7%) as independent predictors of postoperative survival. Freedom from structural valve dysfunction, prosthetic valve endocarditis, reoperation, and valve-related mortality and morbidity were 86% +/- 4%, 91% +/- 4%, 81% +/- 4%, and 72% +/- 5%, respectively, at 5 years. The actuarial incidence of valve failure was inordinately high with the Hancock pericardial valve (p less than 0.05). Freedom from thromboembolic events (78% +/- 8% at 5 years) was significantly lower in patients with poor ventricular function (ejection fraction (less than 0.20, 54% +/- 20%; ejection fraction greater than 0.60, 73% +/- 11%; p less than 0.05). Survival after mitral valve replacement was determined by age and left ventricular function. Premature failure of the Hancock pericardial valve resulted in an unacceptable rate of valve-related complications. PMID- 2322062 TI - Computerized potential distribution mapping: a new intraoperative mapping technique for ventricular tachycardia surgery. AB - This study evaluated potential distribution mapping as a method for localizing the site of origin of ventricular tachycardia (VT). In contrast to conventional activation time maps, potential distribution maps require less editing and thus can be more automated and rapidly processed for interpretation of multiple beats of VT. As a series of potential distribution maps during VT is required for detailed analysis, an on-line computerized system was designed to display potential distribution maps sequentially at 1-ms intervals as a color movie. Potential distribution maps and activation time maps were constructed from 182 epicardial and endocardial unipolar electrodes during 12 episodes of reproducible monomorphic VT in 9 dogs four to six days after experimental myocardial infarction (mean cycle length, 162 +/- 21 ms). At the onset of each depolarization during VT, a potential minimum abruptly developed on the surviving epicardium and another on the surviving endocardium of the left ventricle, both immediately adjacent to the subendocardial infarct. These two minima on the initial potential distribution maps corresponded to the sites of earliest epicardial and endocardial activation breakthrough recorded on the activation time maps. These two minima subsequently expanded or moved into the adjacent area and coincided with the spread of activation fronts on the epicardial and endocardial surfaces. Thus, the rapid display of sequential, computerized potential distribution maps of multiple beats of VT provides a dynamic means of identifying the site of origin of VT, and therefore should facilitate intraoperative mapping. PMID- 2322063 TI - Free arterial graft as internal mammary artery-Y complex. AB - Because of excellent surgical results obtained with in situ internal mammary artery grafts, recent efforts have been made to extend the use of arterial conduits. In this study 2 cases of coronary revascularization using free internal mammary artery and gastroepiploic artery grafts as an internal mammary artery-Y complex are described. We believe that complete revascularization with only arterial conduit can be achieved more widely by using this technique. PMID- 2322064 TI - Management of major tracheal hemorrhage after repair of complex congenital heart defects. AB - Two patients with complex congenital heart defects (a 4-year-old with transposition of the great arteries, ventricular septal defect, and left ventricular outflow tract obstruction and a 3 1/2-year-old with double-outlet right ventricle, subpulmonary stenosis, and complete atrio-ventricular septal defect) suffered multiple major hemorrhages from the tracheobronchial tree (28 and 7 bleeding events, respectively). Successful management included tracheostomy, sedation and paralysis, systemic hypotension, and systemic hypothermia for a period of seven days. Both patients survived. PMID- 2322065 TI - Echocardiographic diagnosis and surgical treatment of postpartum pulmonary embolism. AB - Pulmonary embolism remains a problem in the United States in terms of both morbidity and mortality. New diagnostic modalities to make rapid diagnosis are now available, and allow for bedside diagnosis of pulmonary embolism without the use of pulmonary angiography. As a reference, a case involving a postpartum patient is reviewed. Use of echocardiography, a device readily available even in small institutions, allowed for early diagnosis and institution of therapy in this particular case and in others. Diagnostic features of pulmonary embolism are discussed and the literature is reviewed. PMID- 2322066 TI - Traumatic intercostal pulmonary hernia. AB - Traumatic intercostal pulmonary hernia is a rare sequel to injury, especially in children and where there is no penetrating wound. Spontaneous regression of these hernias has been reported and conservative management has been advocated. We describe a case in which a smooth-walled intercostal defect and lung hernia that did not regress developed in a child. This was successfully repaired with a Gore Tex (expanded polytetrafluoroethylene) patch. Repair is advisable in such cases, but operation can be delayed to allow possible resolution. PMID- 2322067 TI - Multiple congenital aneurysms of the atria. AB - Aneurysms of both the left and right atria are very rare congenital abnormalities. A 3-year-old boy underwent operation with preoperative diagnosis of aneurysms of both atria and supraventricular tachyarrhythmia. The multiple aneurysms were resected during cardiopulmonary bypass. The patient was asymptomatic after operation and has maintained sinus rhythm. PMID- 2322068 TI - Venous cannulation for high-flow femorofemoral bypass. AB - A simple technique is described for reliable passage of a large-diameter venous cannula from a femoral venotomy into the right atrium, to facilitate high-flow femorofemoral bypass. PMID- 2322069 TI - Forceps extraction of permanent pacing leads. AB - With the advent of tined transvenous cardiac pacing leads, the complete extraction of pacing leads in the treatment of an infected cardiac pacing system has become increasingly difficult. A method is described for the extraction of permanent pacing leads from the heart using alligator forceps inserted transvenously through the right internal jugular vein, grasping the lead near its insertion point in the cardiac muscle. PMID- 2322070 TI - Traumatic rupture of the thoracic aorta. PMID- 2322071 TI - Retrograde coronary sinus cardioplegia in redo aortocoronary bypass. PMID- 2322072 TI - Thymectomy for myasthenia gravis. PMID- 2322073 TI - [Are medical genetics eugenic?]. PMID- 2322074 TI - [Characteristics of paroxysmal atrial tachycardia in infants according to the age of onset]. AB - Seventy consecutive patients hospitalized before 1 year of age for reentrant paroxysmal atrial tachycardia (PAT) were studied according to the age of onset of arrhythmia making 3 distinctive groups: group I: 10 patients in whom onset of the arrhythmia occurred during foetal life; group II: 39 infants whose arrhythmia appeared during the first month of life and group III consisting of 21 patients in whom tachycardia began between 1 and 12 months of age. The characteristics and the consequences of the arrhythmia as well as the patients' course and the different treatments used were analysed. Foetal tachycardias were characterized by a slower heart rate. Episodes were most often short and repetitive as opposed to post-natal tachycardias which were often prolonged but somewhat unfrequent. Before the age of 3 months the occurrence of heart failure was more frequent. Independently of the age of onset, 43% of patients presented Wolff-Parkinson White syndrome (WPW), which disappeared spontaneously in 1 out of 3 cases. The existence of WPW syndrome was correlated with late relapses. PMID- 2322075 TI - [Partial atrioventricular block and prolonged QT interval in 4 premature infants receiving diphemanil]. AB - Four premature infants presenting with episodes of bradycardia in the first weeks of life were given diphemanil. One of them received an overdose accidentally. Paradoxically, this induced a permanent bradycardia leading to the discovery of a grade II A-V block as well as a prolonged QT interval. Discontinuation of the drug resulted in a prompt normalization of these changes. It is felt that this anticholinergic therapy may have caused a prolongation of the QT interval and, therefore, a partial A-V block in case of sinus tachycardia. Thus, such a therapy should not be given to young premature infants without having checked the QT interval on a ECG tracing and having made sure that it is adapted to the actual heart rate. It is also advised to reduce usual doses. PMID- 2322076 TI - [Cholestasis caused by ulcerative Vater's papillitis in a child with AIDS]. AB - A case of cholestasis induced by ulcerative papillitis in an 11 month-old boy with AIDS is described. Resolution of cholestasis has been achieved with medical therapy. The authors underline the necessity of repeated endoscopic follow-up to evaluate the risk of secondary papillary stenosis, a complication usually observed in adults. PMID- 2322078 TI - [Nosocomial Legionnaires' disease in children. Preventive measures]. AB - Two immunocompromised children, aged 3 years and 1 1/2 month, developed an hospital-acquired Legionnaire's disease. In one case, Legionella pneumophila serotype 1 was identified by culture in pleural fluid; LP1 was isolated in all the warm water samples in the hospital. Clinical, epidemiological data and laboratory findings are discussed. PMID- 2322077 TI - [Meningo-encephalomyelitis in Lyme disease]. AB - A case of isolated central nervous system involvement in Lyme disease is described. A 13 year-old boy developed progressive spastic quadraparesis, chronic lymphocytic meningitis with a low CSF glucose concentration and demyelinating lesions of the white matter on MRI. The diagnosis was proved serologically by high antibody titers against Borrelia burgdorferi (BB) in the serum (1:5, 120) and CSF (1:1,280). There was evidence of specific intrathecal immune response against the BB antigen. The patient was treated with penicillin G and then ceftriaxone. The CSF abnormalities quickly improved but improvement of the neurologic symptoms was gradual and to date still incomplete. PMID- 2322079 TI - [Giardia lamblia infestation at child day care centers. Nutritional impact in infested children]. AB - Seventy-five children attending a day care center (42 girls and 33 boys, aged from 6 to 65 months) were surveyed for excretion of Giardia lamblia cysts. Cyst excretion was found in 17 (23%) of the children, 9 of whom were still positive 6 months later. Weight, height and arm skinfold thickness of each subject were obtained and compared to normal values in the Quebec population; a questionnaire concerning gastrointestinal symptoms was filled out for each child. No difference in weight, height, skinfold thickness or in frequency of gastrointestinal symptoms was found when comparing cyst excretors to children with a negative stool examination. This study suggests that G. lamblia infestation has little or no nutritional impact. This should be confirmed by a larger study. PMID- 2322080 TI - [Pharmacologic efficacy of sodium alginate suspension on gastro-esophageal reflux in infants and children]. AB - Eighty-three children presenting with symptomatic gastro-esophageal reflux (GER) (48 males, 35 females, aged 15 days to 57 months (mean = 7 months) were assessed by pH monitoring. All showed acid pathological GER on the 3 hours post-prandial esophageal pH measurement (% of time at pH less than 4 greater than 4.2) and all had a second pH measurement within the following 3 hours after intake of a single (5 ml) dose of sodium alginate (AGS). AGS administration was followed by a highly significant reduction (p less than 0.00001) of all pH measurement variables: a) Percentage of time spent at pH less than 4 returned to normal with a mean 11.7% to 4.8%; that is a 52.5% improvement (median); b) Total number of reflux reduced on average from 8.9 to 5.0: that is a 35% improvement (median); c) Mean duration of reflux reduced on average for 4 to 2 min; that is a 60% improvement (median). In 76 patients hourly monitoring of % of time spent at pH less than 4 shows that hourly improvement persists. PMID- 2322081 TI - [Visceral leishmaniasis disclosed by pigmentary lithiasis]. PMID- 2322082 TI - Alcoholism--North America and Asia. A comparison of population surveys with the Diagnostic Interview Schedule. AB - The Diagnostic Interview Schedule (DIS) is a highly structured instrument that enables lay examiners to gather the clinical information necessary to generate psychiatric disorders according to the DSM-III, Feighner, and Research Diagnostic Criteria. It was developed originally as the diagnostic interview for the Epidemiologic Catchment Area (ECA) survey. Because it adheres to DSM-III and can be used by lay interviewers, thus making it practical for studies involving large samples, it has been used for other population surveys in North and South America, Europe, and Asia. This investigation compares the epidemiology of DSM III-defined alcohol abuse and addiction in DIS-based population surveys cross nationally (in St Louis, Mo; Edmonton, Canada; Puerto Rico; Taipei City, Taiwan; and South Korea). We found considerable variation in the lifetime prevalence of alcoholism but a similarity in the age of onset, the symptomatic expression, and the associated risk factors. We also found an inverse correlation between the prevalence of alcoholism and the strength of the association of the risk factors we examined. The work described herein demonstrates the utility of consistent definition and method in cross-cultural psychiatric research. The substantive findings have implications for the definition of alcoholism and for a better understanding of genetic and environmental interactions in its etiology. PMID- 2322083 TI - Clinical importance of age at onset in type 1 and type 2 primary alcoholics. AB - Alcoholics have been proposed to be comprised of subtypes who differ in their age at onset and in type 1 vs type 2 characteristics. This study examined whether the clinical course of primary alcoholics was associated with age at onset as well as the type 1-vs-type 2 classification scheme. Interviews with 171 consecutive primary alcoholic men entering an alcohol treatment program revealed that age at onset of alcoholism was correlated with alcohol, drug, and childhood criminality problem histories. Neither classification of these alcoholics into discrete type 1 and type 2 categories nor placing them along a continuum of type 2 characteristics was consistently associated with severity of clinical histories. These findings underscore the clinical importance of age at onset and suggest the possibility that the type 2 prototype might represent a separate diagnosis, antisocial personality disorder, and not alcoholism itself. PMID- 2322084 TI - Nicotine exposure among nondependent smokers. AB - Most theories of dependence imply that repeated exposure to an addictive drug leads inexorably to dependence. We examined nicotine exposure in "tobacco chippers," who smoke regularly without developing dependence. Blood samples were obtained before and after 10 chippers (smoking up to 5 cigarettes per day) and 12 dependent smokers (20 to 40 cigarettes per day) smoked a cigarette. Chippers' blood nicotine levels increased significantly, in amounts equaling those of dependent smokers. Assays of cotinine (a long-lasting nicotine metabolite) also suggested that chippers' per-cigarette nicotine absorption equaled that of dependent smokers. Chippers' cotinine levels were also compared with those of heavy smokers (38 cigarettes per day) whose consumption was reduced to 5 cigarettes per day in a previously published study. The heavy smokers compensated by tripling their per-cigarette nicotine intake. Chippers did not seem to be compensating; their cotinine values equaled those expected when regular smokers were not compensating for reduced cigarette availability. PMID- 2322085 TI - Morning vs evening light treatment for winter depression. Evidence that the therapeutic effects of light are mediated by circadian phase shifts. AB - Bright light exposure has been found to alleviate the symptoms of recurrent winter depression in many patients. The mechanism of light therapy may involve shifts in the timing (phase) of circadian rhythms. In this study, morning light exposure (which shifts rhythms earlier) was compared with evening light exposure (which shifts rhythms later) in a double-blind, crossover design. The onset of melatonin secretion in the evening was measured under dim light conditions as a marker for circadian timing (phase) before and after each treatment. Eight patients with winter depression and five control subjects were studied. Morning light was found to be significantly better than evening light in reducing depressive symptoms. At baseline, there was a trend for the onset of melatonin production to be later in the patients than in the controls. Morning light shifted the melatonin onset significantly earlier in the patients but not the controls. Our findings suggest that patients with winter depression have circadian rhythms that are abnormally delayed and that bright light therapy benefits winter depression by providing a corrective advance. PMID- 2322086 TI - Seasonal independence of low prolactin concentration and high spontaneous eye blink rates in unipolar and bipolar II seasonal affective disorder. AB - Twenty-four subjects with seasonal affective disorder (SAD: bipolar II, n = 14; unipolar, n = 10) and 20 normal controls were assessed for early follicular basal serum prolactin (PRL) concentration in winter and summer. Luteal basal PRL concentration was assessed in winter. The PRL values represented the mean of three values derived during a 45-minute period. A subset of 17 subjects with SAD and 11 controls were also assessed for spontaneous eye blinking via a polygraphic recording in winter and summer. In winter, compared with controls, subjects with SAD were characterized by significantly lower follicular (10.1 vs 4.5 micrograms/L, respectively) and luteal (14.4 vs 7.4 micrograms/L, respectively) PRL values and by significantly higher eye blink rates (30 vs 61 blinks per 3 minutes, respectively). In summer, controls and subjects with SAD showed similar significant differences in follicular PRL values (9.3 vs 3.9 micrograms/L, respectively) and eye blink rates (25 vs 67 blinks per 3 minutes, respectively). No significant differences in PRL values or eye blink rates were found between the bipolar II and unipolar forms of SAD in either season. Results were discussed in terms of dopamine functioning. PMID- 2322087 TI - X-chromosome markers and manic-depressive illness. Rejection of linkage to Xq28 in nine bipolar pedigrees. AB - Numerous reports have been published concerning linkage of X-chromosome markers of the q28 region (including protan and deutan color blindness [CB] and glucose-6 phosphate dehydrogenase deficiency) to manic-depressive illness. We studied nine bipolar pedigrees (in which there was no male-to-male transmission) in an attempt to detect linkage, using three tightly linked polymorphic DNA loci, DXS15, DXS52 and F8C (factor 8 gene), all of which are closely linked to the CB and glucose 6 phosphate dehydrogenase classic Xq28 markers. Linkage to this region of Xq28 could be excluded unequivocally in these nine families. When these data were combined with our earlier series of bipolar pedigrees, informative for either protan or deutan CB, a total of 14 bipolar pedigrees have been studied, with no evidence of linkage or heterogeneity. At a recombination fraction (theta) of 1%, this series had greater than 95% power to detect linkage if only 50% of the pedigrees studied were linked to the CB region. Our failure to confirm the previously reported linkage of manic-depressive illness to the CB region of the X chromosome indicates that this linkage is not as common as previously suggested. PMID- 2322088 TI - Close linkage between panic disorder and alpha-haptoglobin excluded in 10 families. AB - We previously reported a lod score of 2.3 suggesting linkage between panic disorder and the alpha-haptoglobin locus on chromosome 16q22 in 26 pedigrees. In the present study we tested for linkage between alpha-haptoglobin and panic disorder in 10 new pedigrees and excluded a gene for panic disorder from 6 centimorgans (recombination fraction, 0.06) surrounding the alpha-haptoglobin locus. The data were analyzed under a variety of assumptions about the transmission of panic disorder, and linkage was excluded by all genetic models but one. When lod scores from the present set of 10 pedigrees were pooled with those from the first 26, no evidence of genetic heterogeneity was found, and the maximum lod score was 0.67 at a recombination fraction of 0.17. Taken as a whole, the present findings do not support the presence of a disease gene for panic disorder closely linked to the alpha-haptoglobin locus on chromosome 16q22. PMID- 2322089 TI - How old is the lesion presenting as schizophrenia? Relevance to the laterality question. PMID- 2322090 TI - What is left of attention in schizophrenia? PMID- 2322091 TI - Cholecystokinin-4 and panic. PMID- 2322092 TI - Pigmented myomatous neurocristoma of the uterus. PMID- 2322093 TI - Residency training program in laboratory medicine. PMID- 2322094 TI - The accuracy of frozen-section diagnoses in 34 hospitals. AB - We compared the diagnoses from intraoperative frozen-section consultation with the final diagnosis using permanent tissue sections from 34 hospitals throughout North America. Participating pathologists who provided data from their practices volunteered for a pilot study of Q-Probes, a modular quality assurance program of the College of American Pathologists, Skokie, III. During 4 weeks, 186 pathologists evaluated 1952 frozen-section cases and deferred diagnoses to the final permanent sections in 77 cases (3.9%). Concordance between frozen-section and the final histologic diagnoses was 96.5%; whereas the mean and median concordance rates for participating institutions were 96.8% and 97.4%, respectively. Of 67 discordant diagnoses, 29 occurred from sampling of nonrepresentative tissue specimens, and 29 from diagnostic misinterpretations. The pathologists indicated that the diagnostic discordance had little or no effect on patient care in 94% of cases. We conclude that the North American pathologists studied interpret frozen sections with exceedingly high accuracy, approximating that reported from teaching hospitals. PMID- 2322095 TI - A laboratory medicine residency training program that includes clinical consultation and research. AB - We describe a laboratory medicine residency training program that includes ongoing interaction with both clinical laboratories and clinical services as well as significant research experience. Laboratory medicine residents serve as on call consultants in the interpretation of test results, design of testing strategies, and assurance of test quality. The consultative on-call beeper system was evaluated and is presented as an effective method of clinical pathology training that is well accepted by the clinical staff. The research component of the residency program is also described. Together, these components provide training in real-time clinical problem solving and prepare residents for the changing technological environment of the clinical laboratory. At the completion of the residency, the majority of the residents are qualified laboratory subspecialists and are also capable of running an independent research program. PMID- 2322096 TI - Alveolar epithelial hyperplasia and adenocarcinoma of the lung. AB - To understand better the pathogenesis of peripherally occurring well differentiated adenocarcinoma of the lung in relation to alveolar epithelial hyperplasia (AEH), immunohistochemical, morphometric, and electron microscopic studies were done on surgical pathologically examined cases of lung cancer. Cases with interstitial pulmonary fibrosis were excluded so that the effects of diffuse scarring of the lung on the development of neoplasia were eliminated. Of 70 specimens with various types of pulmonary carcinomas, 15 were found to have coexistent typical or atypical AEH lesions. No area of transition from AEH to neoplasm was found. The immunohistochemistry studies showed significant differences in the reactions of carcinoembryonic and blood group antigens between typical and atypical AEH lesions, but no significant differences could be obtained between atypical AEH lesions and adenocarcinoma. However, the morphometry of the mean nuclear areas revealed a highly significant difference between atypical AEH lesions and adenocarcinoma. Electron microscopy showed many Clara granules in atypical AEH cells. The results did not prove that AEH lesions are precancerous, but the presence of Clara granules in atypical AEH cells raises speculation on the histogenetic relationship between AEH and pulmonary adenocarcinoma. PMID- 2322097 TI - Serum antibodies to oxidized low-density lipoprotein and ceroid in chronic periaortitis. AB - The incidence of serum antibodies to human low-density lipoprotein, to oxidized low-density lipoprotein, and to ceroid extracted from human atheroma was assessed in 100 subjects using an adaptation of the enzyme-linked immunosorbent assay technique. Patients with chronic periaortitis, subclinical chronic periaortitis, and ischemic heart disease, and "elderly control" individuals were compared with young, healthy adults. Provided that precautions were taken to prevent oxidation of the low-density lipoprotein during the assay, antibodies were not found to native human low-density lipoprotein. Antibodies to oxidized low-density lipoprotein or ceroid, usually both, were detected in all 20 patients with clinical chronic periaortitis, in 17 of 20 patients with subclinical chronic periaortitis, in 12 of 20 patients with ischemic heart disease, and in 10 of 20 elderly control subjects. Binding inhibition studies showed cross-reactions between oxidized low-density lipoprotein and ceroid. Western blotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that in some patients with clinical chronic periaortitis, these antibodies were directed against breakdown products of apolipoprotein B that resulted from oxidation of low-density lipoprotein. Antibodies to oxidized low-density lipoprotein or ceroid were not detected in healthy young adults. These findings show that chronic periaortitis is accompanied by autoallergy to ceroid, which is probably at least partly composed of low-density lipoprotein oxidized within the human atherosclerotic plaque, and that a number of middle-aged and elderly people without chronic periaortitis also have such antibodies. PMID- 2322098 TI - The lack of clinical utility of white blood cell differential counts and blood morphology in elderly individuals with normal hematology profiles. AB - An investigation of 462 patients aged older than 65 years with normal hematology profiles revealed 105 individuals with unsuspected abnormalities in the white blood cell differential count, peripheral blood film, or platelet count. In only 8 patients would this information have resulted in additional patient testing or other changes in management. The availability of instrumentation providing an automated platelet count would have decreased the number of patients experiencing a change in management to 5. In no instance did physicians believe that an individual patient's clinical outcome would have been altered by a knowledge of the unexpected abnormalities or the anticipated management changes. In an ambulatory adult population with normal hematology profiles, there is limited clinical value in pursuing further studies, such as a white blood cell differential count or an examination of the red blood cell morphology. PMID- 2322099 TI - Calibration as a source of imprecision in cholesterol testing. Ramifications for patient risk classification. AB - Routine calibration of a cholesterol assay system may compromise rather than improve precision. We compared an enzymatic assay on a centrifugal analyzer using a fixed factor with a factor recalculated from the response of standards assayed with each run. Over 36 batch runs, using three quality control materials, we found no statistically significant difference between the two methods in mean value, but in every case the fixed factor values were significantly more precise. With the risk classification system in effect at the time of the study, 32 (9.4%) of 342 patient serum specimens assayed for cholesterol were classified differently based solely on the method of data reduction. Thus, recalibration of our cholesterol assay system contributed to greater imprecision and to discrepancies in classification of patients' risk levels. PMID- 2322100 TI - Characterization of ductular hepatocytes in end-stage cirrhosis. AB - The existence of facultative stem cells in the liver has been advocated based on observations from models of carcinogenesis in rat liver. Observations of human liver material from cases of fulminant hepatitis have shown the presence of ductular hepatocytes expressing markers of both hepatocytes and bile duct cells. We describe the morphologic features and antigenic expression of a population of ductular hepatocytes identified in a patient with end-stage cirrhosis resulting from hepatitis B infection and secondary biliary cirrhosis. By conventional light microscopy and electron microscopy, ductular hepatocytes were seen to form pseudoductules within periportal areas. Using immunohistochemical methods, these ductular hepatocytes were found to be positive for both the hepatitis B surface antigen and bile duct epithelial cytokeratin, phenotypic markers classically restricted to expression on hepatocytes and bile duct epithelium, respectively. These findings show definitively that ductular hepatocytes are intermediate cells bearing morphologic and phenotypic characteristics of both hepatocytes and bile duct epithelium. The presence of these cells indicates the existence of facultative stem cells in the adult mammalian liver. PMID- 2322101 TI - The risk of an overt hemolytic transfusion reaction following the use of an immediate spin crossmatch. AB - The major crossmatch must include an anti-human globulin test, unless the transfusion recipient has no apparent significant unexpected antibodies, in which case the use of only an immediate spin crossmatch method is considered acceptable. However, a minority of laboratories utilize only an immediate spin crossmatch as their routine major crossmatch, possibly because contemporary antibody screening tests occasionally miss detecting some unexpected antibodies, and these missed antibodies are more often detected by the anti-human globulin crossmatch than by the immediate spin crossmatch. In the present study, 20 hospitals were surveyed to determine how often an acute hemolytic transfusion reaction would occur when only an immediate spin crossmatch was used as the major crossmatch method. During the study period, 1.3 million immediate spin crossmatches were performed, and five patients experienced acute overt hemolytic transfusion reactions that were believed to be caused by antibodies that were missed by both the antibody screening test and immediate spin crossmatch (one hemolytic event per 250,000 immediate spin crossmatches). The implicated antibodies were anti-Jka, anti-Wra, anti-C, anti-c, and anti-Kpa. These survey data demonstrate that the routine crossmatching of blood using an immediate spin crossmatch may rarely result in an acute hemolytic transfusion reaction if the antibody screening cells used during pretransfusion compatibility testing fail to detect some clinically significant red blood cell antibodies. PMID- 2322102 TI - Hepatolithiasis in hereditary hemorrhagic telangiectasia. AB - Hereditary hemorrhagic telangiectasia is a rare, hereditary fibrovascular dysplasia. We report a case associated with hepatolithiasis. Hepatolithiasis, relatively common in East Asia, is rare in the West. The association of the two conditions has not been previously reported. In this case, vascular malformations in the liver gave rise to arteriovenous and arterioportal fistulas, causing arteriovenous shunting and protal hypertension, respectively. Abnormal blood flow is the proposed mechanism for the hepatic fibrosis and nodular regeneration. Hepatic fibrosis, by causing stenosis of large intrahepatic bile ducts, bile stasis, and secondary infection, is the hypothesized mechanism for calculus formation. Hepatolithiasis ultimately caused death from acute bacterial cholangitis and septicemia. PMID- 2322103 TI - Osteomyelosclerosis with granulocytic sarcoma of chest wall. Morphological, ultrastructural, immunologic, and cytogenetic study. AB - A case of granulocytic sarcoma presenting as a soft-tissue tumor in the chest wall in a patient with osteomyelosclerosis is reported. The tumor mass was detected by a computed tomographic scan during an investigation of the cause of chest pain in a 58-year-old man. Biopsy of the mass showed findings compatible with either a large-cell lymphoma or a granulocytic sarcoma. The latter was confirmed by naphthol-ASD-chloracetate esterase stain and electron microscopic examination. Immunologic study of the tumor mass showed expressions of membrane/cytoplasmic CD 13 and CD 15 antigens. In addition, the tumor cells coexpressed CD 19, although all other T- and B-cell-associated antigens were absent. Cytogenetic study showed translocation t(1;7)(q11;q11) with a net deletion of the entire long arm of chromosome 7 and duplication of the long arm of chromosome 1. Peripheral blood examination showed typical leukoerythroblastosis with teardrop poikilocytosis, large hypogranular platelets, and 0.11 myeloblasts. A bilateral iliac bone marrow biopsy at this time showed osteomyelosclerosis. The patient was treated with hydroxyurea followed by local irradiation, resulting in marked reduction in the size of the tumor and in the pain. He was asymptomatic without any progression in hematologic parameters 10 months after the initial diagnosis. PMID- 2322104 TI - Physiatric therapeutics. 1. Physiatric evaluation. AB - This self-directed learning module highlights advances in physiatric evaluation. It is part of the chapter on physiatric therapeutics for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. This section discusses goniometry, muscle strength testing, and functional and disability evaluation. PMID- 2322105 TI - Physiatric therapeutics. 2. Therapeutic heat and cold, electrotherapy, and therapeutic exercise. AB - This self-directed learning module highlights the general concepts and advances in therapeutic heat and cold, electrotherapy, and therapeutic exercise. This article is part of the chapter on physiatric therapeutics for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. Special advances include lasers in medicine and the description of the appropriate type of exercise for weight control. PMID- 2322106 TI - Physiatric therapeutics. 3. Traction, manipulation, and massage. AB - This self-directed learning module highlights advances in this topic area. It is part of the chapter on physiatric therapeutics for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. This section discusses physiologic effects of, and indications and contraindications for, traction, manipulation, and massage. Advances covered in this section include hypotheses of pain relief in manipulation. PMID- 2322107 TI - The next generation of surgical residencies. What are the challenges and the opportunities? AB - I suggest restructuring general surgical residencies to facilitate training of surgical specialists and subspecialists. Basic surgical education for 1 or 2 years should provide a foundation of fundamental cognitive, technical, and patient management skills useful for all surgery residents, regardless of discipline. Intermediate surgical education for an additional 2 or 3 years should amplify cognitive, technical, and clinical skills and senior responsibility in general surgery for individuals entering a general surgical subspecialty or for advanced general surgery training. Residents seeking a career in advanced general surgery would take 2 additional years of training in advanced surgery. Such individuals could pursue additional subspecialty training and research experience to qualify as academic surgical scientists. Implementation of such innovations in general surgical education awaits the cooperative joint efforts of appropriate accrediting and certifying organizations, specialty societies, and surgical program directors. PMID- 2322108 TI - Hepatic parenchymal oxygen tension following injury and sepsis. AB - Hepatic blood flow and splanchnic oxygen consumption were measured in 16 injured (n = 6) or septic (n = 10) patients and compared with values in 16 normal volunteers. Sepsis and injury appeared to stimulate an increase in blood flow and oxygen utilization, with the highest levels observed in the septic group. Patients with sepsis exhibited a 72% and 60% increase in hepatic blood flow and splanchnic oxygen consumption, respectively, compared with normal volunteers. Application of these data to the Krogh-Erlang tissue model indicates that despite an increase in oxygen delivery to the splanchnic bed during sepsis, it becomes more sensitive to hypoxic/ischemic events compared with other patient groups. This is indicated by a reduced centrilobular and increased critical oxygen tension. The major factor responsible for this is the regional hypermetabolism present in sepsis. This analysis emphasizes the critical importance of maintaining oxygen transport in critically ill patients with sepsis. PMID- 2322109 TI - Source of plasma chromogranin A elevation in gastrinoma patients. AB - Chromogranin A (Cg A) is a protein that is coreleased with peptide hormones from gut endocrine cells and tumors. Plasma levels of Cg A, pepsinogen group I, and gastrin were measured in 31 patients with gastrinoma. Mean Cg A level in 10 patients with gastrinoma who were not operated on was 169 +/- 32 ng/mL, while in 9 control patients it was 28 +/- 5 ng/mL. In 18 patients with gastrinoma with residual tumor after total gastrectomy, the mean Cg A level was 45 +/- 6 ng/mL, and in 10 patients with normal gastrin levels after total gastrectomy and tumor excision, the mean Cg A level was 40 +/- 4 ng/mL. In 7 patients in whom pregastrectomy and postgastrectomy Cg A levels were measured, the mean reduction was 94 +/- 27 ng/mL, or 66%. There was no correlation between Cg A levels and amount of tumor, presence of metastases, or multiple endocrine neoplasia type I syndrome. There was a significant correlation between Cg A and pepsinogen I levels but no correlation between Cg A and gastrin levels. The results suggest that the elevated plasma Cg A levels in patients with gastrinoma are determined primarily by the trophic effects of gastrin on gastric enterochromaffinlike cells rather than by corelease from the gastrin-producing tumor itself. PMID- 2322110 TI - Neutrophil chemotactic activity in human gastric secretions. AB - To study levels of neutrophil chemotactic activity in human gastric secretions, these secretions were collected via the endoscope during elective esophagogastroduodenoscopy. Fresh samples were then prepared for the neutrophil chemotactic assay with the use of human peripheral neutrophils in modified Boyden chambers. Mean maximum chemotactic activity was 45.8% +/- 11.2% in patients with gastric inflammation compared with only 10.1% +/- 4.2% in patients with normal results of endoscopic examination. The chemotactic factors responsible for this chemotactic activity may play a role in the recruitment of neutrophils to areas of gastric mucosal injury. PMID- 2322111 TI - Changes in gallbladder volume do not affect cystic duct resistance. AB - To our knowledge, the relationship between gallbladder volume and cystic duct function has not been studied. We hypothesized that changes in gallbladder volume would influence cystic duct resistance. The effect of gallbladder volume changes on cystic duct resistance to both prograde (emptying) and retrograde (filling) steady-state flow was tested in 12 dogs under basal cholecystokinin-stimulated conditions utilizing a multiport catheter with a highly compliant balloon placed within the gallbladder fundus. Gallbladder volume was regulated by varying balloon volume from empty to just beyond physiologic distention. Cystic duct resistance was not affected by balloon volume under basal or stimulated conditions or by the direction of perfusate flow. This study demonstrated no relationship between gallbladder volume and cystic duct resistance and did not demonstrate a cystic duct sphincter mechanism at physiologic gallbladder volumes. PMID- 2322112 TI - Pancreaticoduodenectomy. University experience and resident education. AB - A radical pancreaticoduodenectomy offers the best chance for survival in patients with periampullary and pancreatic malignant neoplasms. A pancreaticoduodenectomy has educational value since complex pancreatic operations are demanding and important to the training of surgical residents. Increased pancreaticoduodenectomy experience (per surgeon) has been associated with improved outcomes. We examined the hypothesis that residents who are supervised by faculty surgeons can perform pancreaticoduodenectomies with acceptable outcomes. From 1976 to 1987, 127 pancreatic resections were performed by 81 residents who were supervised by 15 faculty surgeons in four teaching hospitals. A pancreaticoduodenectomy was performed on 61 patients. All residents served as an operating surgeon on a pancreatic resection, and 58 (82%) performed pancreaticoduodenectomies. The mortality for the pancreaticoduodenectomies was 8%, with a 36% major complication rate. A pancreaticoduodenectomy can be performed safely by residents under supervision. A review of the results identifies the means of improving outcomes. These results justify the preservation of a pancreaticoduodenectomy as an important experience for residents. PMID- 2322113 TI - Protein differences in human pancreatic cancer cell lines with diverse metastatic potential. AB - High-resolution two-dimensional polyacrylamide gel electrophoresis was performed on the pancreatic cell lines SG, SG-R, FG, and L3.5, which when injected into the spleen of nude mice produced hepatic metastases in 0%, 20%, 64%, and 100% of the animals, respectively. A total of 981 proteins were quantitatively identified. In the highly metastatic lines, 13 proteins were present in statistically significant greater quantities, while 4 proteins were present in statistically significant greater quantities in the cell lines with a low metastatic potential. Two proteins were unique to the highly metastatic lines, while 16 proteins were unique to the lines with a low metastatic potential. These results suggest that there are considerable quantitative and qualitative differences in the cellular proteins of human pancreatic cancer cell lines with a varying metastatic potential and imply a biochemical basis to tumor heterogeneity and metastases. PMID- 2322114 TI - The cause of coagulopathy after peritoneovenous shunt for malignant ascites. AB - Thirty-five patients with malignant ascites who received a peritoneovenous shunt were studied to determine the type and duration of postoperative coagulopathy. Coagulation factors were measured before and on the first and third day after the placement of a Denver peritoneovenous shunt; 1 to 10 L of ascites was removed at operation. Levels of platelets, antithrombin III, plasminogen, antiplasmin, fibrinogen, and factors V and VIII decreased by the first postoperative day but did not change further through the third day. The levels of fibrinolytic split products increased on day 1 but were lower by day 3. The platelet count reduction by the third day correlated with the hematocrit change (-0.031). The prothrombin and activated partial thromboplastin times remained normal postoperatively. The patterns of change were similar for patients with positive (n = 18) and negative (n = 17) ascites cytologic findings, with elevated (n = 24) and normal (n = 11) preoperative fibrinolytic split product levels, and elevated bilirubin value (greater than 25 mumol/L; n = 9), and no jaundice (n = 26). Bleeding did not occur. The data indicated that plasminogen-rather than thromboplastin-activated fibrinolysis occurred and that platelet reduction was largely dilutional. The reactions were not progressive when ascites was removed operatively. PMID- 2322115 TI - Effects of atherosclerosis on the cutaneous regional and microcirculatory response to ischemia. AB - The cutaneous vascular response to gravity load is abnormal in atherosclerosis. In this study we compared the macrocirculatory and microcirculatory response to ischemia in atherosclerotic smokers, nonatherosclerotic smokers, and healthy nonsmokers. Using videodensitometry, the capillary blood velocity of hallux nail fold capillaries was measured at rest and following 1 minute of ankle cuff occlusion. Blood-flow velocity of the dorsal metatarsal artery was measured by ultrasound Doppler. Resting dorsal metatarsal artery velocity and capillary blood velocity of atherosclerotic subjects were lower than those of nonatherosclerotic smokers and nonsmokers. The dorsal metatarsal artery velocity and capillary blood velocity increased in each group following occlusion. Peak postocclusion dorsal metatarsal artery velocity was lower in the atherosclerotic subjects, but peak capillary blood velocity was not significantly different among groups. Atherosclerosis does not alter the mechanisms of reactive hyperemia in either the macrocirculation or the microcirculation. The magnitude of hyperemia is diminished at the macrocirculatory level. PMID- 2322116 TI - Alterations of gene expression in human colorectal cancer. Biological implications. AB - Alterations in gene expression associated with colorectal cancer have been difficult to study because mucosal cell progenitors are not available in culture. We therefore examined specific genes in approximately 100 human colon cancer cell lines using complementary DNA probes and found profound alterations and heterogenity of gene expression in human colorectal carcinoma. Our data imply that understanding human colorectal cancer will not be accomplished by studying one or two oncogenes in a limited number of cell lines or fresh human tissue. More appropriate postulates of transformation to dictate experimental design may include the investigation of proposed three-dimensional structural changes of interface chromatin or other generalized structural relationships that could predispose to an aberrant gene expression program during transformation. Furthermore, focusing on mechanisms of initiation and defining the molecular genetic markers of gastrointestinal mucosal initiation should lead to a more focused set of genetic, rather than epigenetic, mechanisms that underlie oncogenic transformation. PMID- 2322117 TI - Early physiologic predictors of injury severity and death in blunt multiple trauma. AB - The importance of admission physiological and biochemical variables was modeled on data from 185 patients with blunt liver trauma with regard to their significance in prediction of mortality. The variables used were admission Glasgow Coma Score, base excess (or deficit), arterial lactate, Injury Severity Score, and initial 24-hour volume of blood required for replacement. Each variable was modeled as a predictor of survival alone and in combination, using a linear logistic model. In any two-variable combination, Glasgow Coma Score had a high likelihood ratio for prediction representing the influence of brain injury. But as a single variable reflecting the probability of death, both base excess (LD50 = -11.8 mmol/L) and initial 24-hour volume of blood (LD50 = 5.4 L) were highly significant. A combined logistic model of admission Glasgow Coma Score and base excess had the greatest likelihood of accurate prediction of outcome: P death = e lambda/l + e lambda; where lambda = -0.21(Glasgow Coma Score) 0.147(base excess) + 0.285. Testing of this predictive model on data from 323 additional patients with multiple trauma who had pelvic fracture as their index injury also showed it to be a highly significant early predictor of outcome. PMID- 2322118 TI - Is there a circulating proteolysis-inducing factor during sepsis? AB - Muscles from fed or 72-hour fasted rats were incubated in the presence of plasma from septic rats, recombinant interleukin 1 alpha (rIL-1 alpha), or recombinant tumor necrosis factor alpha (rTNF alpha), and breakdown of total and myofibrillar protein was assessed by determining release of tyrosine and 3-methylhistidine, respectively. Septic plasma stimulated total protein breakdown in muscles from 72 hour fasted rats by 10% to 20%, while myofibrillar protein breakdown was not affected. When septic plasma was added to muscles from fed rats, neither tyrosine nor 3-methylhistidine release was altered. Various concentrations of recombinant interleukin 1 alpha or recombinant tumor necrosis factor alpha did not affect total or myofibrillar protein breakdown. Since septic plasma did not stimulate myofibrillar protein breakdown, the role of a circulating factor for muscle proteolysis during sepsis remains unclear. PMID- 2322119 TI - APACHE II score does not predict multiple organ failure or mortality in postoperative surgical patients. AB - A clinical study was undertaken to evaluate the ability of the APACHE (acute physiology and chronic health care) II system to predict the development of multiple organ failure syndrome and subsequent mortality. The study was conducted in a university general surgery intensive care unit using the admission APACHE II score. Over a 1-year period, 92 patients qualified for the study, 24 of whom survived, 69 of whom suffered multiple organ failure syndrome, and 68 of whom died. The APACHE II score did not predict the development of multiple organ failure syndrome or mortality with clinical utility and significantly underestimated the potential for the development of multiple organ failure syndrome. Factors that did predict the development of multiple organ failure syndrome and mortality were the time-dependent changes in the PaO2-to-fraction of inspired oxygen ratio and serum lactate, creatinine, and bilirubin levels. Better markers of cell injury are needed for use in decision making and quality assurance analysis in surgical patients. PMID- 2322120 TI - The Budd-Chiari syndrome and hepatic veno-occlusive disease. Recognition and treatment. AB - In a review of 29 patients who were surgically treated by combined hepatic and portal decompression for intractable ascites, 18 were identified as falling into the category of the Budd-Chiari syndrome, with varying causes. Of this group, 2 patients were distinguished by the classical hepatic venous endophlebitis described by Chiari and later by Bras et al. Recently, this disease entity has been recognized as being due to the toxic effects of pyrrolizidine alkaloids contained in the Senecio and Crotolaria plants. In the first of these two cases the patient had emigrated from Jamaica and was exposed to "bush trees," but no chemical measurements were done. The second patient had consumed a large amount of comfrey teas, which were shown to contain high levels of pyrrolizidine alkaloids. These two cases add further weight to the existing evidence of the toxic effect of these alkaloids, and also demonstrate the effectiveness of hepatic and portal decompression. PMID- 2322121 TI - Excellent shoulder function is attainable after partial or total scapulectomy. Analysis at prolonged follow-up. AB - We reviewed six cases of primary sarcomas requiring scapulectomy within the past 13 years in the Surgery Branch of the National Cancer Institute, Bethesda, Md. Five of these patients returned for evaluation of disease status, evaluation of functional defects as determined by muscle group testing, and assessment of daily living skills and limitations. We demonstrated excellent shoulder function with partial scapulectomy and significant impairment with the additional loss of the glenoid fossa. In addition, we developed a thorough method of postoperative evaluation. Involvement of rehabilitation therapists before and after operatively is integral to this process in preparation for surgery and subsequent treatment. PMID- 2322122 TI - Adenomyoma of the common bile duct. AB - Adenomyomas are rare pseudotumors of the extrahepatic biliary tract. Their microscopic appearance does not differ significantly from similar malformations of the peritoneal cavity. We describe a patient who presented with obstructive jaundice and who was treated successfully with a surgical resection and a hepaticojejunal anastomosis. PMID- 2322123 TI - Vertebral artery pseudoaneurysm. A rare complication of subclavian artery catheterization. AB - The present case report details a previously unreported complication of subclavian vein catheterization, vertebral artery pseudoaneurysm. Attention to this problem was brought about in the patient by the development of stridor and dysphagia noted 5 days following placement of the subclavian catheter. A computed tomographic scan of the neck revealed a superior mediastinal, contrast-enhancing mass in the region of the right subclavian artery with a "bull's-eye" sign suggestive of a pseudoaneurysm. Arteriography subsequently proved the pseudoaneurysm to be of vertebral origin. The pseudoaneurysm was ligated via a neck incision together with a median sternotomy to obtain vascular control. The evaluation and treatment options of this problem are discussed. PMID- 2322124 TI - Diagnosing myocardial contusion. PMID- 2322125 TI - The morphological substrate of cerebral asymmetry: the problem of its measurement. PMID- 2322126 TI - Natural killer cell activity in patients with dementia of the Alzheimer type. PMID- 2322127 TI - Epilepsy and suicide. PMID- 2322128 TI - Pimozide therapy for trigeminal neuralgia. PMID- 2322129 TI - Tubular aggregates in skeletal muscle associated with neoplastic disease. PMID- 2322130 TI - Are high-protein diets effective in McArdle's disease? PMID- 2322131 TI - Cognition and white matter changes on magnetic resonance imaging in dementia. AB - In a prospective magnetic resonance imaging and cognitive study of 38 demented patients and 15 control subjects, 11 of 27 patients with Alzheimer's disease and 8 of 11 patients with vascular dementia had significant periventricular hyperintensities. Memory and language testing in the early investigation of dementia is useful to distinguish patients with or without periventricular hyperintensities on magnetic resonance imaging. Patients without periventricular hyperintensities are worse on memory and conceptualization tests than patients with periventricular hyperintensities, who tend to be worse on comprehension and attention tests. These differences in cognitive pattern are present between patients with different pathogenesis who are otherwise matched for dementia severity. Language and some nonverbal cognitive deficits correlate with the extent of cortical and ventricular atrophy in Alzheimer's disease. PMID- 2322132 TI - Regional cerebral blood flow in patients with leuko-araiosis and atherosclerotic carotid artery disease. AB - The relation between white-matter lesions (WMLs), demonstrated with magnetic resonance imaging, and regional cerebral blood flow (CBF), measured with dynamic positron emission tomography and [18F] fluoromethane, was investigated in 20 patients with atherosclerotic disease of the internal carotid artery. There was no correlation between the extent of small patchy WMLs and hemispheric CBF, but hemispheric CBF was significantly reduced in 5 patients with multiple large or confluent lesions. Distinct focal cortical CBF reductions were observed when large WMLs (greater than 5 mm) were located directly beneath the cortex, whereas large WMLs in deeper white matter were associated with a more diffuse decrease of cortical perfusion. There was no evidence of preferential CBF reduction in vascular border zones with increasing severity of WMLs or stenosis of the internal carotid artery. The side of previous transient ischemic symptoms correlated significantly with hemispheric CBF asymmetries, but not with asymmetries of WMLs and internal carotid artery stenosis. It can be concluded from these results that the presence of small patchy WMLs shown by magnetic resonance imaging cannot be used as evidence of impaired cerebral perfusion, while large lesions indicate clinically relevant cerebrovascular disease affecting cortical blood flow. PMID- 2322133 TI - Neuropsychological impairments associated with lesions caused by tumor or stroke. AB - Populations of patients with strokes or tumors constitute the most frequently used subjects in neuropsychological research, and these populations are often combined when the investigation aims at establishing brain-behavior relationships. We compared these two populations with respect to their neuropsychological profiles. Seventeen subjects with tumors were individually matched to subjects with unilateral strokes on the basis of lesion location. Despite close matching of lesions, there were major differences in the neuropsychological impairments of the two groups, eg, all subjects with stroke in the left hemisphere had more severe language defects than did their counterparts with tumors, and some tumor subjects performed normally on all neuropsychological tests. These findings demonstrate that the cognitive and/or behavioral consequences of tumors or strokes in similar locations can be radically different. The two patient types should be treated separately for the purpose of neuropsychological research. PMID- 2322134 TI - The development of independent foci in epileptic patients. AB - The electroencephalograms of 309 unselected epileptic patients were reexamined to ascertain the incidence of independent secondary discharges. In 41 patients (13%), a simple one-sided focus, without evidence of independent secondary discharges, was found (group 1); in 33 patients (11%), an epileptic focus with certain evidence of independent secondary discharges was found (group 2). These two groups were compared with respect to multiple variables (eg, seizure type, time course of the epileptic illness, site of foci, medication, neurological status), and significant differences between the two groups were obtained (eg, with respect to frequency of seizures, duration of seizures, number of anticonvulsive drugs being taken, and in other respects). Our findings are compared with earlier work, and it is concluded that they do not support the conventional models of secondary epileptogenesis. PMID- 2322135 TI - The blink reflex in patients with idiopathic torsion dystonia. AB - The blink reflex and its recovery cycle were examined in 57 patients with idiopathic dystonia affecting different parts of the body. The group comprised 9 patients with generalized and 15 with segmental forms, 19 with torticollis, and 14 with focal arm dystonia. None had blepharospasm. The duration and amplitude of the R2 component of the blink reflex showed only minor changes. However, its recovery cycle to paired supraorbital nerve stimuli was abnormal in all groups of patients, except those with focal arm dystonia. These findings may be interpreted as showing abnormal control of the interneuronal networks mediating the blink reflex in patients with dystonia affecting sites other than the facial muscles. The fact that the principal changes were seen in patients with torticollis, and generalized or segmental dystonia, suggests that the extent of dystonia (rather than the severity) and, therefore, the close proximity to the cranial muscles was important in determining the extent of the abnormal interneuron function. PMID- 2322136 TI - Late recovery of auditory comprehension in global aphasia. Improved recovery observed with subcortical temporal isthmus lesion vs Wernicke's cortical area lesion. AB - This study examined the relationship between recovery of auditory comprehension in global aphasia patients after 1 year post onset, and temporal lobe lesion in Wernicke's cortical area vs temporal lobe lesion in the subcortical temporal isthmus area. Computed tomographic scans and language behavior were examined in 14 right-handed globally aphasic stroke patients with lesion in the left hemisphere. Nine patients had large cortical/subcortical frontal, parietal, and temporal lobe lesion that included more than half of Wernicke's cortical area (FPT cases). Five patients had large cortical/subcortical frontal and parietal lobe lesion, but only subcortical temporal lobe lesion, including the temporal isthmus (FPTi cases). All patients were tested acutely at 1 to 4 months post onset and again at 1 to 2 years post onset. There was a significantly greater increase in the amount of recovery that had taken place after 1 to 2 years post onset for the FPTi group vs the FPT group in the overall Boston Diagnostic Aphasia Examination (BDAE) Auditory Comprehension Z score. In four of the five FPTi cases, the late BDAE Auditory Comprehension Z scores were above -0.5 (mild to-moderate comprehension deficits). Most recovery was in single-word comprehension. In eight of the nine FPT cases, the late BDAE Auditory Comprehension Z-scores were below -0.5 (moderate-to-severe comprehension deficits). There was no significant difference between the two groups in recovery of spontaneous speech, repetition, or naming, where severe deficits remained in most cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322137 TI - Cognition in early human immunodeficiency virus infection. AB - Relatively little is known about cognitive changes in early human immunodeficiency virus (HIV) infection. This study examined cognitive functioning in 46 HIV-positive gay men relative to an age and education equivalent group of 13 HIV-negative gay men. The HIV-positive men were asymptomatic except for lymphadenopathy or T4 counts less than 700. The cognitive battery measured language, memory, visuospatial, information processing speeds, reasoning, attention, and psychomotor processes. The HIV-positive group was significantly slower in processing information and performed significantly less well than the HIV-negative group on certain verbal memory measures. Deviations of 1 as well as 2 SDs from the norm/control group mean on four or more tests were observed in 43% and 22% of the HIV-positive subjects, respectively, compared with 8% and none of the HIV-negative subjects, respectively. The results suggest that cognitive inefficiency occurs in a subsample of individuals during early HIV infection. PMID- 2322138 TI - Controlled clinical trials in cerebrovascular disease. A misused tool. PMID- 2322139 TI - Multicenter trials in stroke. PMID- 2322140 TI - A patient with progressive myelopathy and antibodies to human T-cell leukemia virus type I and human immunodeficiency virus type 1 in serum and cerebrospinal fluid. AB - A 52-year-old human immunodeficiency virus type 1-seropositive bisexual black man was evaluated at UCLA because of the recent onset of progressive lower-extremity weakness. Initial neurologic examination showed that the patient's distal weakness was greater than his proximal weakness, with bilateral foot drop and electrophysiologic evidence of denervation in the distal lower extremities. Magnetic resonance imaging of the brain and spinal cord disclosed no abnormalities. Subsequent neurologic evaluation 8 months later showed a myelopathy, with progression of lower-extremity weakness, spasticity, and flexor spasms, and urinary incontinence, as well as the peripheral neuropathy noted previously. A second magnetic resonance imaging scan of the brain showed patchy foci of increased signal intensity in white matter and cortex, with mild generalized cerebral and cerebellar atrophy and no lesions in the spinal cord. Specimens of the patient's serum and cerebrospinal fluid contained antibodies to human immunodeficiency virus type 1. Additionally, specimens of his serum and cerebrospinal fluid were tested for antibody to human T-cell leukemia virus type I by Western blotting and radioimmunoprecipitation, and found to be positive for human T-cell leukemia virus type I gag, env, and tax antibodies. The primary cause of severe myelopathy in this patient may be infection with human T-cell leukemia virus type I rather than with human immunodeficiency virus type 1. Treatment with prednisolone resulted in improvement of the lower-extremity weakness, reduction in flexor spasms, and slower but significant improvement in urinary symptoms. Patients who are infected with human immunodeficiency virus type 1 and have unusual motor findings should be tested for concomitant human T cell leukemia virus type I infection. PMID- 2322141 TI - Axial length and the response to strabismus surgery. PMID- 2322142 TI - Retinal artery embolism following cardiac catheterization. PMID- 2322143 TI - Protracted uveitis as the initial manifestation of Wegener's granulomatosis. PMID- 2322144 TI - Quantitative pupillometry of relative afferent defects in glaucoma. PMID- 2322145 TI - Sodium hyaluronate and giant retinal tears. PMID- 2322146 TI - Propionibacterium acnes orbital abscess. PMID- 2322148 TI - Free-floating cyst of the retrolental space. PMID- 2322147 TI - Tonic upgaze in infancy. PMID- 2322149 TI - Leukemic infiltrate appearing as periorbital cellulitis. PMID- 2322150 TI - Medical liability tort reform receives congressional attention. PMID- 2322152 TI - The ocular hypotensive effect of the topical carbonic anhydrase inhibitor L 671,152 in glaucomatous monkeys. AB - L-671,152, a new potent water-soluble inhibitor of human carbonic anhydrase II in vitro, was applied topically to cynomolgus monkey eyes in which glaucoma had been produced by argon laser photocoagulation of the trabecular mesh-work. Intraocular pressure was measured at 0 hours, 0.5 hours, and hourly for 8 hours in eight eyes for 2 baseline days, 1 day receiving the vehicle and 5 days receiving therapy with 2% L-671,152 twice a day, after initial single-dose trials of various concentrations. Intraocular pressure was not significantly different comparing baseline and vehicle-treated days. Significant intraocular pressure reductions occurred from 1 to 8 hours after the first dose, and lasted for at least 16 hours after the second dose. The reduction in intraocular pressure became more pronounced from day 1 to day 5 at each time interval. The mean (+/- SEM) maximum reduction in intraocular pressure was 7.8 +/- 2.1 mm Hg on day 1 and 10.1 +/- 2.4 mm Hg on day 5 at 3 hours after administration, comparing the intraocular pressure in drug-treated and vehicle-treated eyes. L-671,152 has a longer duration of action than does previously studied MK-927 in glaucomatous monkeys. It appears to have great clinical potential. PMID- 2322151 TI - Botulinum treatment of strabismus following retinal detachment surgery. AB - Twenty patients with strabismus and diplopia following surgery for retinal detachment were treated by botulinum toxin injection of the eye muscles. Twelve patients had regained fusion with elimination of diplopia in the primary position at the time of examination, 5 to 96 months after treatment (mean, 24 months). Three patients had partial diplopia elimination, and five patients continued to have diplopia. PMID- 2322153 TI - Effects of Vasocon-A in the allergen challenge model of acute allergic conjunctivitis. AB - The ophthalmic combination product of 0.05% naphazoline hydrochloride and 0.5% antazoline phosphate (Vasocon-A) was evaluated as an antiallergic agent in 100 subjects with a known allergic history to cat dander, ragweed, or bluegrass pollen. Three independent study sites were used. The allergen challenge model of acute allergic conjunctivitis was selected to assess the agent as it provided a standardized and precise way to measure drug effectiveness for this indication. In a double-masked randomized fashion, the subjects were assigned to one of three groups that received one drop of Vasocon-A in one eye and one drop of either 0.05% naphazoline (group 1), 0.5% antazoline (group 2), or placebo (group 3) in the contralateral eye. After 10 minutes, the dose of allergen shown to elicit a 2+ redness and itching reaction was instilled bilaterally. Signs and symptoms of allergic conjunctivitis were evaluated after 3, 5, and 10 minutes. Subjects were then rechallenged 2 hours after drug administration to assess the duration of action of the agents. Vasocon-A was found to significantly inhibit all five major signs and symptoms of allergic conjunctivitis: itching, redness, chemosis, lid swelling, and tearing, for more than 85% of the comparisons when compared over time with placebo, naphazoline alone, or antazoline alone. The results of this study indicate that the combination of naphazoline and antazoline was more effective in inhibiting redness than naphazoline and more effective in inhibiting itching than antazoline. These findings support the use of such a combination for the treatment of allergic conjunctivitis. PMID- 2322154 TI - Bilateral diffuse uveal melanocytic proliferation in patients with occult carcinoma. AB - The development of multiple, round or oval, subtle, red patches at the level of the pigment epithelium in the posterior ocular fundus and their striking early hyperfluorescence angiographically are characteristic features of the bilateral diffuse uveal melanocytic proliferation syndrome. They may be accompanied by severe visual loss and may antedate the appearance of multiple melanocytic tumors, retinal detachment, and cataract in these patients with occult systemic carcinomas. These hyperfluorescent patches are caused by focal damage to the pigment epithelium overlying an intact choriocapillaris and diffuse benign nonpigmented uveal melanocytic infiltration of the outer choroid. We suggest that outer retinal damage may not be primarily caused by melanocytic proliferation, but rather by toxic and immune factors generated by interaction between a systemic carcinoma and congenital melanocytosis of the uveal tract. We report the longest survivor of this disorder to date (102 months). PMID- 2322155 TI - Development of keratoconus after contact lens wear. Patient characteristics. AB - A retrospective review of 398 eyes of 199 patients with keratoconus revealed 106 eyes of 53 patients with an association between contact lens wear and the development of keratoconus. The absence of keratoconus at the time of contact lens fitting was confirmed by slit-lamp examination, keratometry readings, and manifest refraction. Keratoconus was diagnosed after a mean of 12.2 years of contact lens wear. This group was compared with patients with sporadic keratoconus with either no history of contact lens wear or a history of contact lens wear after the diagnosis. They were older at the time of diagnosis, had central vs decentered cones, and had a tendency toward flatter corneal curvatures. We believe that these patients suggest that long-term contact lens wear is a factor that can lead to keratoconus. PMID- 2322156 TI - Reproducibility of normal corneal power measurements with a keratometer, photokeratoscope, and video imaging system. AB - To determine the reproducibility of currently available instruments for measuring corneal power, two investigators measured comparable locations on 18 normal human corneas using a keratometer (Bausch & Lomb, Rochester, NY), the Corneascope (Kera Corp, Santa Clara, Calif), and the Corneal Modeling System (Computed Anatomy Inc, New York, NY). (For the two keratoscopes, average powers around rings at comparable locations were used.) Comparisons made between instruments at the significance level of .05 indicated that the keratometer was more reproducible than the Corneal Modeling System and the Corneascope, and the Corneal Modeling System was more reproducible than the Corneascope. Of the 31 rings projected on the surface of each cornea by the Corneal Modeling System, rings 2 through 13 were read reasonably reproducibly in that 76% of the measurements on these rings differed by no more than 0.5 diopter. The Corneal Modeling System (software version 1.16) is 83% as reproducible as a keratometer reading at approximately the edge of the 3-mm central zone on normal human corneas and provides information about corneal topography in a more reproducible and visually useful manner than the other two instruments. PMID- 2322157 TI - Prevalence and significance of optic disc hemorrhage in a longitudinal study of glaucoma. AB - We determined the prevalence of hemorrhage within 1 disc diameter of the optic nerve head by masked examination of stereoscopic color and red-free fundus photographs in a multilayer study of 1123 patients. At the first (baseline) examination, disc hemorrhages were present in none of the normal subjects (0 of 661), 0.44% (6/1377) of "glaucoma suspect" subjects, and 2.44% (3/123) of glaucomatous eyes. Disc hemorrhage prevalence in glaucomatous eyes was significantly higher than in normal or glaucoma suspect eyes. Glaucoma suspect eyes with disc hemorrhage, compared with matched suspect eyes without disc hemorrhage, had a larger mean vertical cup-disc ratio, an increased rate of nerve fiber layer atrophy 1 year following disc hemorrhage, and a higher rate of conversion to initial visual field loss (numerically higher conversion though not statistically significant). While the number of eyes with disc hemorrhages in this study is small, in a patient with glaucoma or ocular hypertension, disc hemorrhage appears to be associated with a greater likelihood of ongoing damage. The low disc hemorrhage prevalence in an unselected population limits its usefulness as a screening tool for glaucoma. PMID- 2322158 TI - Cone dysfunction in a subgroup of patients with autosomal dominant cerebellar ataxia. AB - Four patients with autosomal dominant cerebellar ataxia and retinal degeneration underwent neurologic and ophthalmologic examinations and computer-assessed corneal electroretinography. Previous reports described progressive panretinal degeneration initially involving the cones and subsequently spreading to the rods. By contrast, all our patients displayed evidence of selective dysfunction of the cone system in one or two successive electroretinograms, irrespective of their age or duration of visual symptoms. Color vision testing, funduscopy, and fluorescein angiography suggested a cone dystrophy. Within the period of observation only one patient showed progression of cone dysfunction. In patients with hereditary ataxias, quantitative electroretinography provides an objective and sometimes early indication of retinal degeneration and helps to characterize it. PMID- 2322159 TI - Histopathologic validation of Fourier-ellipsometry measurements of retinal nerve fiber layer thickness. AB - We describe a new technique for the measurement of retinal nerve fiber layer thickness and compare its results with histopathologic measurements in the same eyes. For these studies, two fixed monkey eyes were incised and placed on a pedestal in a plastic viewing dish. The eyes were perfused to maintain a pressure between 10 and 20 mm Hg. An ellipsometer, an optical device used to measure the change in polarization of light (retardation), was implemented in a laser tomographic scanner to obtain polarization data from the two monkey retinas. For the 15 measured locations, retardation ranged between a mean (+/- SD) of 0.9 degrees +/- 1.8 degrees and 23.7 degrees +/- 0.3 degrees. Subsequently, retinal nerve fiber layer thickness was measured at the imaged points in epoxy resin embedded sections by an observer masked to the ellipsometry data. These values ranged between 20.4 microns and 213.9 microns. There was an excellent correlation (R = .83) between retardation and the histopathologic measurement of retinal nerve fiber layer thickness. Quantitating retinal nerve fiber layer thickness may enhance discrimination between glaucomatous and normal eyes earlier than is currently available by anatomic and functional approaches. PMID- 2322160 TI - Topical nonsteroidal agents and corneal wound healing. AB - The effects on corneal wound healing of two topical nonsteroidal anti inflammatory agents, flurbiprofen sodium (0.03%) and diclofenac sodium (0.1%), and the topical corticosteroid, prednisolone sodium phosphate (1%), were evaluated in masked, controlled rabbit studies. Healing of epithelial scrape wounds was significantly retarded in all three treatment groups for the first 3 days after wounding. There was no difference in the epithelial healing rate between the two nonsteroidal or corticosteroid treatment groups. Clinical grading of epithelial quality, conjunctival hyperemia, keratitis, stromal edema, and corneal haze were similar in all groups. There was a significant early decrease in the iritis score in the diclofenac treatment group. The strength of 2-mm central penetrating corneal trephination wounds and the collagen content of these wounds were similar in all groups. Both the topical nonsteroidal anti inflammatory agents and the corticosteroid used in the preparations and dosages investigated in this study decreased early epithelialization of scrape wounds but had no apparent effect on corneal stromal healing. No toxic effects of the various drugs were found. PMID- 2322161 TI - Ocular penetration of cyclosporine A in the rat eye. AB - The treatment of rats with cyclosporine A by the oral, intraperitoneal, or intravenous routes results in a high level of the drug within the liver and spleen in all cases. The blood level varies and is highest after intravenous injection. The eyes of these animals do not show any significant accumulation of the drug, either extraocularly or intraocularly except for the rats treated by intravenous injection, where radioactive cyclosporine A is detected within the chorioretinal complex. Even in these cases, however, no radioactivity is observed within the vitreous. After local application of 2% cyclosporine A eye drops in olive oil, a high concentration of the drug is found in the cornea and conjunctiva only. No intraocular penetration is observed in these cases. However, when cyclosporine A eye drops in absolute alcohol are used, high levels of the drug are also found in intraocular tissues. Thus, in the intact eye, the cornea and conjunctiva on the one hand and the blood retinal barrier on the other hand prevent the intraocular penetration of cyclosporine A. PMID- 2322162 TI - Encircling photothrombotic therapy for choroidal Greene melanoma using rose bengal. AB - The photosensitizing dye rose bengal in combination with an argon green laser (514.5 nm) operated at low power was evaluated in 49 rabbit eyes for treatment of experimental choroidal Greene melanoma by circumferential occlusion of the choroidal vasculature. The effects of no treatment, laser alone, and rose bengal alone were observed in 16 control eyes, all of which showed rapid tumor growth. Immediately following rose bengal injection, 3 minutes of continuous irradiation at 20.4 W/cm2 (500-microns spot, 40 mW) applied in three to four circumferential revolutions around the base of tumor nodules, without direct tumor irradiation, produced peripheral vascular occlusion and consequent tumor inhibition. Similar therapy at higher laser intensity (30.6 W/cm2) and with multiple retreatment sessions (28.0 to 30.6 W/cm2) resulted in increased tumor-inhibiting effect. Low dose rose bengal phototherapy did not appear to directly damage ocular tissues adjacent to treatment areas; however, when multiple irradiation sessions were given within a short interval, an increased incidence of retinal detachment was observed. PMID- 2322163 TI - Clearance of experimental vitreous hemorrhage after panretinal cryotherapy is related to macrophage influx. AB - We investigated the effect of panretinal cryotherapy on blood clearance and on the inflammatory cellular response in rabbit eyes with experimental vitreous hemorrhage. Eyes treated with cryotherapy demonstrated less extensive vitreous opacity and more rapid clearance of blood than untreated eyes. The peak inflammatory cellular response measured by counts or radiolabeled cells in the optic nerve was 2.5 times greater in the cryotherapy-treated eyes. Panretinal cryotherapy may promote the clearance of vitreous hemorrhage by stimulating the influx of increased numbers of phagocytic inflammatory cells. PMID- 2322164 TI - Causes of pediatric eye injuries. A population-based study. AB - Eye injuries are an important cause of ocular morbidity in children. We conducted a population-based study of eye injuries requiring hospital admission for children younger than 16 years in the state of Maryland during the 1982 calendar year. The population-based estimate of the incidence of ocular trauma in Maryland children was 15.2 per 100,000 per year (95% confidence interval, 12.8 to 17.7). Male patients outnumbered female patients as victims of eye injuries by a ratio of approximately 4:1; eye injuries in 11- to 15-year-old children occurred at more than twice the rate than for younger children. The most common cause of pediatric ocular trauma was accidental blows and falls (37%). Sports and recreational activities accounted for 27% of all eye injuries, 39% of all nonpenetrating injuries, and 40% of all injuries in 11- to 15-year-old children. A comparison of the causes of eye injuries at statewide specialty trauma centers and community-based hospitals indicated that sports-related injuries were treated at general hospitals more than 10 times more frequently than at the trauma centers. Other important causes of eye injuries were burns (9%), car crashes (11%), and nonpowder firearm accidents (4%). We conclude that the majority of pediatric eye injuries are preventable, and that the implementation of well established safety precautions would greatly reduce this source of visual disability in our nation's children. PMID- 2322165 TI - A fiberoptic stylette for localizing the balloon buckle. AB - A third-generation balloon catheter that accepts a fiberoptic has been developed. The fiberoptic is inserted through the catheter to the center of the balloon when the balloon is in the area of the retinal break. Viewed with the ophthalmoscope light at dim to off, the balloon can be seen glowing through the wall of the eye. The position of the balloon can then be shifted until the glow is precisely under the retinal break. PMID- 2322166 TI - An evaluation by scanning electron microscopy of small dental cutting instruments through use and cleaning. AB - The progressive status of some selected small dental cutting instruments was examined from the time of their unpackaging through routine institutionalized cleaning and sterilizing procedures both before and after first and subsequent use. The cleaning protocol in place at the time involved a phosphoric acid based detergent and ultrasonic cleaning. All assessments were made by scanning electron microscopy. It was found that new burs as unpackaged are unacceptable for use without first being subjected to a cleaning process and that the cleaning procedure utilized was ineffective and unsuitable. Also observed was the potential for gross contamination; the need for subsequent ultrasonic cleaning; and the different rate and nature of deterioration, with use, of the three bur types studied. This study has led to the introduction of modified procedures for the physical cleaning of small cutting instruments in our institution and confirms the usefulness of the scanning electron microscope in the ongoing practice of quality assurance. PMID- 2322167 TI - Amyloidosis with oral involvement. Case report. AB - A patient with chronic renal failure was investigated after complaining of oral discomfort which was found to be due to macroglossia and generalized involvement of the oral soft tissues by amyloidosis. A search for multiple myeloma proved to be positive. She also had a previous history of Carpal-tunnel syndrome. Despite an initial good response to treatment with phenylalanine nitrogen mustard (melphalan hydrochloride), she finally succumbed to end-stage renal failure. PMID- 2322168 TI - Panoramic radiographic survey of hypodontia in Australian Defence Force recruits. AB - Comprehensive dental examinations and panoramic radiographs were used to determine the prevalence of hypodontia in 662 Australian Defence Force recruits. Of the sampled population, 6.3 per cent exhibited some degree of hypodontia (third molar agenesis excluded). Previous studies produced similar results. Third molar agenesis occurred in 22.7 per cent of the sample which again is in agreement with other studies. There was no statistical difference between the sexes in third molar agenesis; however, there was a significant difference with upper second premolars. Females exhibited an extremely low incidence of absence of maxillary lateral incisors. PMID- 2322169 TI - After-hours treatment of anterior dental trauma in Newcastle and western Sydney: a four-year study. AB - This study investigated anterior dental trauma presenting after-hours in Newcastle and western Sydney. During the four-year period 1983-1986, all patients presenting with anterior dental injuries to the Royal Newcastle Hospital (n = 382) or Westmead Hospital (n = 362) on week nights, weekends or public holidays were studied. In both areas, upper central incisors were the teeth injured most frequently. The mean numbers of teeth injured per patient were 1.9 at Newcastle and 2.0 at Westmead. The frequencies of injury types found in Newcastle and Westmead were similar. Luxations and avulsions accounted for 39.5 per cent of injuries at Newcastle and 39.6 per cent at Westmead. In Newcastle, the rate of occurrence of trauma was highest and relatively uniform in the 6-11, 12-17 and 18 23 year age groups. At Westmead, it was highest in the 6-11 year age group, followed closely by the 12-17 year age group. In both centres, the four main causes of trauma were falls, assaults and fights, sports and bicycle accidents. These accounted for 69 per cent of all injuries in Newcastle and for 69.4 per cent at Westmead. This study found a great similarity between Newcastle and western Sydney in relation to the predominant age and sex groups affected, causes of trauma, injury types and numbers and locations of injured teeth per patient. It is suggested that anterior dental trauma presenting after-hours may be more severe, involve more teeth per patient and affect predominantly older age groups than is the situation during normal hours. PMID- 2322170 TI - Localized alveolar ridge augmentation using a connective tissue graft. Case report. AB - The restorative dentist is often faced with difficulties in overcoming functional, cosmetic, and cleansibility requirements when replacing teeth in areas of localized alveolar ridge resorption. A case report is presented highlighting a surgical technique to correct such an alveolar ridge deficit. PMID- 2322171 TI - Silent periods in dysfunction patients: a preliminary study using a novel approach. AB - Strong peri-oral stimulation is known to elicit a transient inhibition in the activity of the jaw-closing muscles. Several reports have claimed that this 'silent period' (SP) is prolonged in patients with temporomandibular joint dysfunction syndromes. In the present preliminary study, the biphasic SP evoked by electrical lip stimulation was tested in single motor units in the masseter muscles of dysfunction patients. In comparison with normal subjects, the pattern of the SP was different in the patients in that the shorter-latency phase predominated over the later phase, whereas the converse is true for normals. PMID- 2322172 TI - Correlation between fracture properties and clinical performance of composite resins in Class IV cavities. AB - One hundred and two Class IV cavities were restored randomly with four composite resins. The restorations were assessed at six months, one year, two years and three years for surface chipping, bulk fracture and incisal wear. The data were correlated with various mechanical properties of the materials. A significant correlation was found between surface chipping/bulk fracture and fracture toughness (P = 0.002), elastic modulus (P = 0.006) and tensile strength (P = 0.045). There was a trend towards an association between incisal wear and both elastic modulus and inherent flaw size. Fracture toughness may be a useful indicator of the clinical performance of composites in Class IV cavities. PMID- 2322173 TI - The effect of fluoride consumption and social class on dental caries in 8-year old children. AB - School dental service data indicate that whilst Melbourne eight-year-old children had worse dental health than similar children in the Geelong area in 1979, the situation in 1985 was the reverse. In order to investigate this, and determine the effects of socio-economic level (SEL), residential history, and fluoride history on dental caries status, 208 eight-year-old children in the Melbourne area and 209 eight-year-old children in the Geelong area were examined for dental caries. A questionnaire was administered to gain details of subjects' exposure to water and supplement fluorides. The SEL of the subjects' school was used in place of individual SEL. A high proportion (46 per cent) of Geelong subjects used a fluoride supplement at some stage, but few continued this for most of their life. Residential history was important, with 2.4 per cent of the Melbourne subjects living most of their life in a nonfluoridated area and 3.4 per cent of Geelong subjects living most of their life in a fluoridated area. There was a significant difference between the dmft in Melbourne and Geelong when only children who had lived all their life in the city in which they were examined and did not use a fluoride supplement were included. A large part of this difference is attributed to water fluoridation in Melbourne. A substantial number of children would benefit from fluoridation of the reticulated water supply in Geelong, particularly those in the lower social classes. PMID- 2322174 TI - Survey of dental practice/dental education in Victoria. Part II. Recent graduates/graduating students. AB - The views of recent graduates and graduating students from the University of Melbourne, School of Dental Science, were sought in regard to their training for registration as dentists. Respondents were requested to indicate the emphasis placed on a number of subjects taught in the dental curriculum over the past ten years in relation to their preparedness for general practice. The priorities to be given to basic science and medical subjects, as indicated by the recent graduates in another section of the survey, were related to the judgment of emphasis given in the undergraduate curriculum. With respect to dental subjects, there were some for which a substantial number of respondents (over 60 per cent in each case) indicated that there was insufficient emphasis given during the undergraduate course. These included both 'Theory' and 'Hands on' aspects of aesthetic dentistry, fixed prosthodontics, occlusion and orthodontics, 'Hands on' aspect of care of the special patient, conservative dentistry, endodontics, medical emergencies and oral surgery and, finally the 'Theory' aspect of equipment design. Students also considered both aspects of ethics and legal matters, 'Hands on' experience for oral function and disorders of oral function and the theoretical aspect of implant dentistry to be deficient. Appreciable numbers of graduates (over 40 per cent for both 'Theory' and 'Hands on') indicated insufficient emphasis on implant dentistry, patient management, equipment design, ethics and legal matters, practice management/administration, practice promotion and professional relationships.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322175 TI - 'An unusual mouthful'. PMID- 2322176 TI - Surveying the 80s and looking ahead into the 90s. PMID- 2322177 TI - Cervicofacial emphysema following dental procedures. PMID- 2322178 TI - Pap smears: quality, not only quantity. PMID- 2322179 TI - Descriptor utilisation review. PMID- 2322180 TI - Tasmanian inter-practice visit study. PMID- 2322182 TI - Jet lag. AB - Jet lag is the loss of wellbeing associated with rapid travel across time zones. An understanding of its causes and the factors which influenced its severity may help in its prevention and management. PMID- 2322181 TI - Recurrent issues in traveller health. AB - The questions concerning the health of travellers discussed in this paper are which antimalarial to prescribe; whether to immunise against hepatitis, typhoid or cholera; and which, if any, antidiarrhoeal to prescribe. PMID- 2322184 TI - Prevention of viral hepatitis. AB - Viral hepatitis is one of the more common potentially serious infections that may be acquired during international travel. Clinically indistinguishable syndromes may be produced by a variety of enterically and parenterally transmitted hepatitis viruses, with widely differing implications and outcomes. Most travel related hepatitis can be prevented by a combination of sensible precautions and appropriate immunoprophylaxis. PMID- 2322183 TI - Rabies and the traveller. AB - Human rabies is an invariably fatal disease once it manifests clinically. The disease, however, is preventable if medical practitioners and potential victims are adequately educated, and if pre-exposure vaccination is used judiciously. The disease has a worldwide distribution and travellers to many areas are at risk. The authors provide information for people who may be at risk through travel, explain how the disease is diagnosed and describe the use of vaccination before and after exposure. PMID- 2322185 TI - Malaria: advice to travellers. AB - Malaria continues to be a major international public health problem but many Australians who travel overseas are ill-informed of the risk of infection and have inadequate protection against this potentially fatal disease. Management is complicated by the resurgence of malaria in areas that have previously had satisfactory control programmes, and the emergence of resistance to chloroquine and other drugs. This article focuses on prevention of malaria in travellers. The more important issue of malaria control for populations residing in endemic areas is beyond the scope of this review. PMID- 2322186 TI - Altitude sickness. AB - Altitude sickness is a clinical syndrome that occurs with abrupt ascents to altitudes of 3000 metres and above. Symptoms include headache, malaise, fatigue, dizziness, anorexia, nausea and vomiting, and oliguria. At higher altitudes more severe illness resulting from pulmonary oedema or cerebral oedema can occur. PMID- 2322187 TI - Mobilisation of subtalar joint of ankle. PMID- 2322189 TI - A death without a diagnosis. PMID- 2322188 TI - Aspirin and coronary heart disease. Clinical applications. AB - Aspirin, which is an effective anti-platelet agent, given in the low dosage of 60 to 100 mg per day appears to be beneficial for patients with a history of unstable angina, myocardial infarction, transient ischaemic attacks and stroke. PMID- 2322191 TI - Patient education. Tinea pedis. PMID- 2322190 TI - Three camels in the car park. PMID- 2322192 TI - Used needles. PMID- 2322193 TI - Liver transplantation: an update for physicians. PMID- 2322194 TI - Rehabilitation for stroke survivors. PMID- 2322195 TI - Paroxysmal cerebellar ataxia. PMID- 2322196 TI - Patients want more information about the drugs they take. PMID- 2322198 TI - The A, B, C, D and E of viral hepatitis: new agents for old diseases. PMID- 2322197 TI - Autologous bone marrow transplantation for acute myeloid leukaemia in remission: a preliminary report. AB - Autologous bone marrow transplantation, using unpurged cryopreserved autologous marrow, was performed on ten adult patients with acute myeloid leukaemia in remission. Seven patients were in first chemotherapy-induced remission of their disease, while three were in later remission. Patients ages ranged from 24 to 52 years, with a median of 38.5 years. Conditioning therapy consisted of oral busulphan 16 mg/kg over four days and intravenous cyclophosphamide 60 mg/kg on two days. Bone marrow cells were thawed and infused two days later. All patients showed signs of marrow engraftment, however this was delayed in comparison with patients receiving allogeneic transplants. All patients developed fever requiring antibiotic therapy and one patient died of overwhelming sepsis. Another patient died of hepatic veno-occlusive disease two months after transplant. Serious, but non-fatal, hepatic complications occurred in two other patients. One patient, transplanted in third remission, relapsed 16 months post-autograft. No other relapses have been seen, with one second remission patient remaining leukaemia free at 24 months, and six first remission patients in continuing remission 11 to 23 (median 20) months post transplant. These encouraging results require confirmation in a randomised clinical trial comparing autologous marrow transplantation versus standard chemotherapy. PMID- 2322199 TI - Bacterial colonisation of the respiratory tract in chronic bronchitis. AB - One hundred and nine subjects with chronic bronchitis were studied prior to winter and without clinical infection, to determine baseline patterns of bacterial colonisation. Qualitative analysis of cultures of oropharyngeal swabs showed little difference from age matched normal controls (17) except for growth of small numbers of Gram negative coliforms in the chronic bronchitic group. Quantitation of bacteria colonising the oropharynx showed small numbers (mean of 10(5) cfu/ml), with no particular bacteria dominating. Haemophilus influenzae was present in 7.3% of throat swabs from chronic bronchitic patients, but the organism was always less than 10% of the total count. Quantitation of bacteria in sputum showed significantly higher numbers (mean 10(7) cfu/ml). H. influenzae was detected in 25.7% of available specimens, and when present constituted greater than 90% of the total count. Biotyping of H. influenzae isolates demonstrated a separate colonisation of the upper and lower respiratory tracts. PMID- 2322200 TI - Hypoxia during bronchoalveolar lavage. AB - The aim of this study was to determine the degree and duration of hypoxaemia during bronchoalveolar lavage (BAL) and to examine the effect of supplemental oxygen on this response. Transcutaneous oxygen tension (PO2) was recorded continuously in 22 patients having bronchoscopy alone (Group 1), and during BAL in patients with a variety of connective tissue disorders. Thirty eight of these patients were breathing room air (Group 2) and 28 were given supplemental oxygen (Group 3). The mean fall in PO2 in Group 1 was 12 +/- 3 mmHg and the PO2 in these subjects rose promptly to the initial value once the bronchoscopy was finished. The mean falls in Groups 2 and 3 were 24 +/- 4 and 32 +/- 5 mmHg and the mean times taken for the PO2 values to return to baseline after the procedure were 47 +/- 9 and 53 +/- 10 minutes respectively. The PO2 fell to less than 60 mmHg in 76% of the patients in Group 2 but in only 25% of those in Group 3. It is recommended that supplemental oxygen be given to all patients having BAL during and for one hour after the procedure and that oxygenation be monitored continuously throughout the bronchoscopy. Arterial blood gases should be always measured prior to bronchoscopy and BAL. In those cases where it is not possible to maintain the PaO2 at 70 mmHg or more the procedure should be undertaken with great care and with due consideration of the risk of the hypoxaemia that may occur. PMID- 2322201 TI - Complications and causes of death in B cell chronic lymphocytic leukaemia: a long term study of 105 patients. AB - The complications and causes of death of 105 patients with B cell chronic lymphocytic leukaemia followed for a median period of 5.5 years are described. Infection and secondary primary malignant tumours were the most common complications and also caused most deaths. S. pneumoniae, S. aureus, S. haemolyticus, E. coli and the zoster-varicella virus accounted for most infections and the lungs, skin and urinary tract were the sites affected. Even trivial infections were potentially serious. Haemolytic anaemia and vascular complications were also common. Older patients tended to have a shorter survival than the mean for the group whereas younger patients fared better. The mean survival was 6.2 years. Analysis confirmed the prognostic value of Rai staging. Advancing disease increased the liability to major infection. Light bone marrow infiltration five years post diagnosis indicated a good prognosis and preservation of normal immunoglobulin levels seemed beneficial. Immunoglobulin deficiency is the factor that correlates best with the frequency, severity and pattern of infection. Early stage disease provides a distinct benefit and there may be advantages in prompt diagnosis, regular assessment by immunoglobulin levels and bone marrow pattern and treatment on the first evidence of advancing disease. Fresh symptoms should be investigated in their own right because of the likelihood of second tumours. PMID- 2322202 TI - Asthma aerosols and CFCs. PMID- 2322203 TI - Unusual pulmonary manifestations of Pneumocystis carinii infection in immunocompromised patients. AB - Three proven cases and one presumed case of Pneumocystis carinii pneumonia are presented in which the radiological appearance mimics tuberculosis. The classic and unusual X-ray findings of P. carinii pneumonia are discussed. PMID- 2322204 TI - The 'shrinking lungs syndrome'--an infrequently recognised feature of systemic lupus erythematosus. AB - Two cases of the 'Shrinking Lungs Syndrome' in patients with systemic lupus erythematosus are described to highlight an infrequently recognised feature of this condition. Respiratory muscle weakness, improved by steroid therapy, was demonstrated in each patient and considered to be the mechanism underlying the respiratory symptoms. PMID- 2322205 TI - Wegener's granulomatosis--use of cyclosporin-A: a case report. AB - Wegener's granulomatosis is a chronic relapsing condition requiring long term immunosuppressive treatment. Periodic exacerbations may require increased dosage of steroids and/or cyclophosphamide. We present a case of a patient with end stage renal failure who had repeated pulmonary cavitating lesions but was unable to tolerate high dose standard therapy. After only a few months with cyclosporin A there was almost complete resolution of his lung lesions. PMID- 2322206 TI - Mucor cerebral abscess associated with intravenous drug abuse. AB - We report on a case of a 26-year-old intravenous narcotic abuser with a primary cerebral mucormycotic abscess caused by Rhizopus oryzae. He was treated with a combination of intravenous and intraventricular amphotericin B and surgical drainage with a successful outcome. There was no evidence that his infection was acquired by the rhinocerebral route, it seems likely that he injected himself with a contaminated batch of narcotic or amphetamine. Mucormycosis presenting in this way has been described previously but this is only the second such case to survive. Early diagnosis and treatment is essential for a favourable outcome in this condition. PMID- 2322207 TI - Endometrial adenocarcinoma presenting as pituitary apoplexy. AB - The novel combination of disseminated primary endometrial adenocarcinoma and a symptomatic pituitary metastasis presenting as pituitary apoplexy is described for the first time. Pituitary apoplexy is an unusual manifestation of metastatic pituitary disease. The more common clinical features of pituitary metastases and an approach to their management are discussed. The usefulness of magnetic resonance imaging in assessing the base of skull is emphasised. PMID- 2322208 TI - Rhodococcus equi and HIV infection. PMID- 2322209 TI - Cytotoxin-negative Clostridium difficile. PMID- 2322210 TI - Another bank: advance or challenge? PMID- 2322211 TI - Aetiology of Dupuytren's contracture. AB - Dupuytren's contracture is a fascinating, deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists for centuries. The aim of this paper is to place in perspective the longstanding associations of age, sex, race, hereditary factors, diabetes and alcohol consumption with the more recent novel investigations at the cellular level. In concert, the findings indicate that a number of factors may lead to the narrowing of palmar fascia microvessels, with localized ischaemia and oxygen free radical release. Oxygen free radicals are likely to damage the surrounding stroma, and stimulate fibroblast proliferation. Proliferating fibroblasts lay down collagen and contract in the lines of stress. The process is likely to encourage further microvessel ischaemia with a positive feedback effect that is consistent with the progressive nature of the condition. PMID- 2322212 TI - Morbidity, mortality and survival following resection for carcinoma of the rectum at Concord Hospital. AB - Colorectal cancer is the most common internal malignancy in Australia, and the rectum is the most common site. The morbidity, mortality and survival of 561 consecutive patients with rectal cancer who had a resection at Concord Hospital during the 16-year period 1971-86 were evaluated. More than half of the operations performed were low anterior resections (LAR), with total abdominoperineal excisions (APE) of the rectum comprising another third. There was a 5.1% mortality rate in LAR patients and a 3.1% mortality rate in the APE group. Respiratory complications, urinary tract infections and wound infections were the most common causes of morbidity in both LAR and APE. The median survival for patients treated by LAR and APE standardized for clinicopathological staging was 111.5 and 47.1 months (A), 79.0 and 65.5 months (B), 41.3 and 28.5 (C), and 14.7 and 12.4 (D), respectively. PMID- 2322213 TI - Current perspectives in staging large bowel cancer. AB - Today, a standardized method of staging that is internationally accepted is urgently needed for the management of patients with colorectal cancer. The use of a uniform, sensitive staging system would greatly improve case selection and avoid unnecessary bias when entering patients into adjuvant therapy trials. This would allow a more accurate evaluation of new treatment protocols and assist in the development of more effective follow-up programmes. PMID- 2322214 TI - Femoral head allograft bone banking. AB - Prior to 1986, there was no uniform protocol for the collection, storage and safe transfer of allograft bone in South Australia. A programme was instituted that resulted in the collection of 100 femoral heads, of which 46 heads were used for a variety of orthopaedic procedures in 31 patients. Wastage was high with 46 femoral heads being discarded because of infection or failure to adhere to all aspects of the protocol. The donor population was found to be a safe source of bone with no cases of unsuspected hepatitis, syphilis, human immunodeficiency virus, or malignancy being detected. There was no infection in recipients. By observing strict criteria for the acceptance of donor bone and aided by a diligent clerical service, this type of allograft can provide a way of dealing with extensive bone deficiency in a number of surgical settings. PMID- 2322215 TI - Hypoxia and hypotension during endoscopy and colonoscopy. AB - Sixty-three patients undergoing oesophagogastroduodenoscopy (OGD) (n = 24) or proctosigmoidocolonoscopy (PSC) (n = 39) had continuous monitoring of arterial oxygen saturation (SaO2), pulse and mean blood pressure (BP). The degree of patient distress, duration, dose of sedative and details of the endoscope and operator were recorded. Marked hypotensive (greater than 40% fall in BP) and hypoxic (greater than 8% fall in SaO2) changes occurred in 13% and 17% of the overall group, respectively. There were no significant differences in fall in BP, SaO2 or pulse between the OGD and PSC groups. The dose of sedative was significantly related to the fall in SaO2 (P less than 0.001) but not to the fall in BP. The falls in both SaO2 and BP were related to the duration of the procedure (P less than 0.001, P = 0.03, respectively). There were no correlations between the degree of hypoxia or hypotension and the patient's age or previous medical history. Hypotension and hypoxia occur in both colonoscopy and OGD and are neither predictable nor usually recognizable clinically. Pulse oximetric and BP monitoring throughout gastrointestinal endoscopy are recommended for maximal safety. PMID- 2322216 TI - Raynaud phenomenon: the Jepson classification. AB - The Jepson classification of Raynaud phenomenon, based on its pathogenesis, is presented. Raynaud phenomenon can be induced in the fingers of the normal hand as the digital vessels are sensitive to the direct effects of cold. A 'local fault' in the digital arteries renders the fingers more susceptible to a fall of environmental temperature, as do limb artery occlusions which impair the digits' ability to maintain their temperature. Other vasoconstrictive influences act similarly to precipitate the onset of the phenomenon. PMID- 2322217 TI - Effect of a thromboxane synthetase inhibitor UK-38,485 on the tolerance of skin flaps of primary ischaemia. AB - The harmful effects of ischaemia or skin flaps were modified using the thromboxane synthetase inhibitor UK-38,485. The epigastric island flaps of Sprague-Dawley rats (n = 288) were subjected to 10, 12 or 14 h of total pedicle occlusion, or 3, 5 or 7 h of venous occlusion of the sole vascular pedicle. Within each time period, rats received intravenous doses of either physiological saline (controls) or UK-38,485 at the beginning or end of the ischaemic episode. Flaps treated with UK-38,485 overall had a higher survival rate than control ischaemic flaps (P less than 0.001). This applied both to total (arterial) ischaemia (P less than 0.001) and partial (venous) ischaemia (P less than 0.01). There was no significant difference between treatment given at the beginning or at the end of the ischaemic episode. These results may be explained by reduced platelet aggregation and thrombosis in the microvasculature due to the lower thromboxane/prostacyclin ratios for treated flaps. The possible inter relationship of the prostanoids with free radical mechanisms in the no-reflow phenomenon is also discussed. PMID- 2322218 TI - Hypernephroma presenting as a lump in the breast. AB - The breast is an unusual site for metastatic disease--generally, the breast lesion appears some time after diagnosis of the primary malignancy. An instance of renal cell carcinoma in a 69 year old woman, which presented primarily as a breast lump, is described. This is only the third such case that has been reported in the literature. PMID- 2322219 TI - Gruntzig balloon catheter dilatation of a severe cervical oesophageal stricture. AB - A 3 year old child with a tight and angulated stricture at the cervical oesophagogastric anastomosis developed marked dysphagia. Initial attempt at Savary-Gilliard bougienage failed because the bougies tended to coil up in the proximal oesophageal pouch. He was subsequently managed successfully by serial Gruntzig balloon catheter dilatation guided by flexible endoscope, with complete amelioration of dysphagia. The methodology of balloon catheter dilatation is described and its advantages for use in high cervical oesophageal stricture discussed. PMID- 2322220 TI - Duodenectomy without pancreatectomy for extensive benign villous adenoma of the duodenum. AB - Villous adenomas of the duodenum are uncommon, but two have been treated recently in Blenheim. One of these was an extensive benign tumour involving most of the second part of the duodenum but causing no biliary tract obstruction. It was treated by pyloric sphincter-sparing duodenectomy without pancreatectomy, with repair by Roux loop to the bile and pancreatic ducts and proximal duodenum. This procedure does not appear to have been described previously. PMID- 2322221 TI - Effect of breeder vaccination on immunization of progeny against Newcastle disease. AB - Two experiments were conducted to determine the effect of breeder vaccination program and maternal antibody on the efficacy of Newcastle disease immunization of 1-day-old chicks. Experimental protocol was the same for both. In the first experiment, broilers were from breeders that were 32 weeks old, and in the second experiment, broilers were from breeders 50 weeks old. Breeders received three live Newcastle disease virus (NDV) vaccines and either a killed vaccine at 18 weeks or continual live boosting at 60-to-70-day intervals through lay. Broilers were vaccinated at 1 day of age with a commercial coarse-spray machine; they were bled, sera were examined for antibody against NDV, and broilers were challenged with virulent NDV at 2, 4, and 6 weeks of age. In the first experiment, maternal antibody was higher in chicks from the younger breeders given the inactivated vaccine, and in the second experiment maternal antibody was higher in chicks from older breeders given continual live vaccines. Higher antibody in 1-day-old broilers resulted in fewer vaccine-induced reactions, less vaccine virus shed, and decreased duration of vaccine-induced immunity from coarse-spray vaccination. PMID- 2322223 TI - Turkey heterophil chemotaxis to Pasteurella multocida (serotype 3,4)-generated chemotactic factors. AB - The purpose of this study was to determine the ability of three strains or isolates of Pasteurella multocida (serotype 3,4) to generate chemotactic factors for heterophils when exposed to pooled turkey serum. Results indicated that each bacterial strain or isolate (M-9, CU, and 86-1913) was associated with the production of chemotactic factors, but the more pathogenic bacterial isolate (86 1913) elicited greater heterophil migration in chemotaxis studies. PMID- 2322224 TI - Somatic serotypes of Pasteurella multocida strains isolated from avian hosts (1976-1988). AB - During the period of 1976-88, 733 strains of Pasteurella multocida isolated from avian hosts were submitted to the National Animal Disease Center for somatic serotyping. The serotypes were determined and are presented in a summarized form in this report. The most common serotypes were 3 (29%); 1 (18%); 3,4 (12%); and 3,4,12 (9%). The 733 strains had been isolated from 25 species of avian hosts; 400 (55%) were from turkeys. The most common serotypes of strains from turkeys were 3 (38%); 3,4 (18%); 3,4,12 (11%); and 4 (4%). PMID- 2322222 TI - Kidney lesions associated with mortality in chickens inoculated with waterfowl influenza viruses. AB - Seventy-six type A influenza viruses recovered from waterfowl in Wisconsin, California, South Dakota, Florida, Texas, Alabama, and Nebraska were tested for virulence in chickens. The challenge to chickens was intravenous inoculation of first-, second-, or third-egg-passage virus. Each of the virus strains was tested separately in three or four chickens. Eighteen of the 76 viruses caused the death of one or more chickens following inoculation. Postmortem lesions were similar in all dead birds. In decreasing order of frequency, gross lesions included: swollen kidneys evident as accentuated lobular patterns, urates in the pericardial sac, and urates on the surface of the liver. Microscopic lesions present in kidneys were consistent with visceral gout. Mortality was associated with inoculations having higher concentrations of infectious virus. These results indicate that the influenza A viruses circulating in duck populations may include strains potentially pathogenic for chickens. PMID- 2322225 TI - Avian eimeria: invasion in foreign host birds and generation of partial immunity against coccidiosis. AB - Four species of avian Eimeria invaded the intestine of foreign host birds in the same areas in which they invaded the natural host. Repeated inoculation (immunization) of chickens with the turkey coccidian, Eimeria adenoeides, partially protected the chickens against a subsequent challenge with 5.8 x 10(4) E. tenella oocysts. At 6 days post-challenge, the weight gain and feed conversion efficiency of the immunized chickens was significantly better than those of the chickens that were not immunized with E. adenoeides. Lesion scores and cellular invasion by the sporozoites were significantly lower in the immunized birds than in the unimmunized group. Electrophoresis and Western blot analysis identified changes in the serum antibody profiles of the chickens that appeared to be associated with the immunization and challenge programs. An antibody or antibodies recognizing a 60,000-molecular-weight antigen of E. tenella sporozoites disappeared when chickens immunized with E. adenoeides were challenged with E. tenella; an antibody or antibodies recognizing a 23,000 molecular-weight sporozoite antigen appeared within 6 days of challenge. Reciprocal studies, in which turkeys were immunized with E. tenella and challenged with E. adenoeides, showed little evidence of protection. PMID- 2322226 TI - Alternative injection sites for a Pasteurella multocida bacterin. AB - Seven different injection sites for a Pasteurella multocida bacterin were evaluated by measuring the immune response and the local tissue reaction. Injection into the ventral surface of the tail or subcutaneously along the dorsal midline of the neck were the most suitable procedures. Ease of application was judged subjectively, and the tail site was found to be easier to inject accurately than the subcutaneous neck site. The tail injection site was found to be the best overall when immune response, tissue reaction, and ease of application were all considered. PMID- 2322227 TI - Cryptosporidiosis in chickens from southern Spain. AB - Cryptosporidiosis in chickens from southern Spain is reported. Cryptosporidia were found in the trachea, esophagus, and epithelium of the bursa of Fabricius in chickens from different regions. In one flock, cryptosporidiosis was associated with respiratory problems and high mortality. In another flock, it was associated with low mortality and weight loss. PMID- 2322228 TI - Potential use of long-acting injectable oxytetracycline for treatment of chlamydiosis in Goffin's cockatoos. AB - To determine the potential use of parenteral therapy in the treatment of chlamydiosis in psittacine birds, the disposition and toxicity of a long-acting oxytetracycline (OTC) was evaluated in Goffin's cockatoos. Following intramuscular and subcutaneous administration of 50 to 100 mg/kg body weight, plasma OTC concentrations of 7 to 15 micrograms/ml were obtained 3 hr following injection and declined with a terminal half-life between 8.9 to 14.7 hr. Plasma concentrations in excess of 1.0 microgram/ml were maintained for 48 to 68 hr. Multiple-dose treatment of 100 mg/kg subcutaneously every 3 days for 30 days caused focal necrosis and scabs at the injection site but no other clinical or serological evidence of adverse effects. Long-term treatment did not result in accumulation or alteration in the disposition of OTC. Based on this study, a dosage regimen of 50 to 100 mg/kg of OTC subcutaneously every 2-3 days would safely maintain plasma concentrations in excess of 1.0 microgram/ml and could potentially be used as an alternative to medicated feeds or daily oral dosing regimens for the treatment of chlamydiosis in psittacine birds. PMID- 2322229 TI - An avidin-biotin enhanced dot-immunobinding assay for the detection of Mycoplasma gallisepticum and M. synoviae serum antibodies in chickens. AB - A dot-immunobinding assay was enhanced by the incorporation of avidin and biotin reagents into the test system (DAB assay). This assay was used to detect serum antibodies to Mycoplasma gallisepticum (MG) and M. synoviae (MS) from chickens. Serum samples were tested by rapid serum plate (RSP), hemagglutination-inhibition (HI), and DAB assay methods. These results were compared. The DAB assay was at least 20 times more sensitive in detecting antibodies for MS and at least 75 times more sensitive in detecting antibodies for MG than the HI test. The DAB assay was as specific as the HI test. The DAB assay was also more sensitive and specific than the RSP test. Some cross-reactions occurred when low dilutions of high-titer sera were used in the DAB assay. Parameters for determining negative, suspicious, and positive samples were established. The DAB assay for MG and MS may have several applications, including use as a screening test and a confirmatory test. PMID- 2322230 TI - Efficacy of toltrazuril and clazuril against experimental infections with Eimeria labbeana and E. columbarum in racing pigeons. AB - The efficacy of toltrazuril in comparison with clazuril on heavy experimental Eimeria labbeana and E. columbarum infections in pigeons was investigated. The minimum required dose of toltrazuril to completely suppress oocyst excretion is 20 mg/kg body weight for 1 day. After treatment with toltrazuril, there was a dose-dependent period during which pigeons remained negative; at a dosage of 35 mg/kg or higher, this period was at least 4 weeks. Clazuril at the recommended dose of 2.5 mg/pigeon resulted in a rapid suppression of oocyst excretion, but oocysts were again observed in the feces 20 days after treatment. The fact that oocysts appeared again in the feces 3 to 5 weeks after treatment can probably be explained only by a persistence of endogenous stages, which are not affected during treatment, rather than by a reinfection. Reinfection of the previously medicated and infected pigeons 30 days after the first infection provided some data on possible induced immunity. PMID- 2322231 TI - Oxidation of 5 beta-cholestane-3 alpha,7 alpha, 12 alpha-triol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid by cytochrome P-450(26) from rabbit liver mitochondria. AB - The mitochondrial cytochrome P-450(26), previously shown to catalyze 26 hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, was found to convert this substrate also into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta cholestanoic acid. The formation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta cholestanoic acid increased with increasing incubation time and enzyme concentration. Addition of NAD+ to the incubation mixture did not increase the formation of the acid. Incubation with 5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol, cytochrome P-450(26), ferredoxin, ferredoxin reductase and NADPH resulted in one major product, 3 alpha,7 alpha, 12 alpha-trihydroxy-5 beta cholestanoic acid. The cytochrome P-450 required both ferredoxin, ferredoxin reductase and NADPH for activity. NADPH could not be replaced by NAD+ or NADP+. PMID- 2322232 TI - Rapid detection of influenza virus H1 by the polymerase chain reaction. AB - We applied a combination of reverse transcription (RT) with the polymerase chain reaction (PCR) for a rapid detection of influenza virus H1 subtype. We amplified a 441 bp segment of relatively high genetic stability of the hemagglutinin gene. Experimental conditions were established using plasmid DNA and infected cell cultures. The test was applied to 28 nasopharyngeal lavages from patients, two of which were positive for influenza virus H1. When the amplified DNA of a positive sample was sequenced we found 97% homology with the recent strain A/USSR/70. PMID- 2322233 TI - Interaction between rat serum phosphorylcholine binding protein and platelet activating factor. AB - The binding of rat serum phosphorylcholine binding protein (PCBP) to platelet activating factor (PAF) has been demonstrated using a HPLC-gel filtration technique. The bulk of the bound [3H]-PAF eluted with a higher molecular weight species of PCBP, possibly an aggregated form of PCBP. A smaller amount of [3H] PAF co-eluted with the major monomeric species of PCBP. Formation of the PCBP-PAF complex was calcium dependent and could be inhibited by phosphorylcholine, suggesting the involvement of the phosphorylcholine binding site on PCBP. Binding of albumin and alpha 1-acid glycoprotein to PAF was not affected by phosphorylcholine or calcium. The specificity of this binding may explain the inhibitory effect of PCBP and related phosphorylcholine binding proteins on PAF induced aggregation of platelets. PMID- 2322234 TI - Spontaneous oscillation of artificial membrane: equivalence in effects of temperature and volatile anesthetic. AB - Oscillatory phenomenon at an oil-water interface in the presence of hexadecyltrimethylammonium bromide (CTAB) has been studied. The oscillation was attributable to successive formation and destruction of surfactant monolayer. According to the temperature elevation, the frequency of the electrical oscillation increased whereas the amplitude decreased. Addition of diethylether increased the frequency and decreased the amplitude. These effects of temperature and anesthetic were analyzed by the theory of the "N"-shaped relationship between surface-pressure and surface-concentration of the surfactant. PMID- 2322235 TI - 2-Chloroacetaldehyde and 2-chloroacetal are potent inhibitors of DNA synthesis in animal cells. AB - The effect of 2-chloroacetaldehyde, CAA, a metabolite of vinyl chloride and 2 chloroacetal, CAC, an ethyl diester of chloroacetaldehyde, on DNA synthesis in animal cells has been investigated. Both compounds drastically inhibited DNA synthesis at 10 to 20 microM. The inhibitory effect of the chemicals appears to be directly on DNA synthesis rather than on the uptake of thymidine or the formation of nucleotides. Residual DNA made in the presence of CAA had an average chain length of 300 nucleotides compared to a length of several thousand nucleotides in the absence of CAA. Synchronization experiments revealed that the inhibitory effect is reversible if 2-chloroacetaldehyde is removed within two hours but not after longer exposures. PMID- 2322236 TI - Does anthramycin bind to Z-DNA as well as to B-DNA? A molecular mechanics study. AB - Molecular mechanics simulations have been presented on the covalent complexes between anthramycin and the decanucleotides d(GCGCGCGCGC)2 and d(GCGCGTGCGC).d(GCGCACGCGC) in the novel Z form, with the drug docked in the minor groove. The simulations predict that anthramycin binds to Z-DNA almost as well as it does to B-DNA, but with a few key differences in the structural aspects of binding. In particular, the 5' orientation of the drug is preferred in the Z form, contrasting with the preference for 3' orientation in the B form and the drug has a left-handed twist. While no experimental studies have been published on the binding of pyrrolo(1,4)benzodiazepines to left-handed forms of DNA, the energy refined stereochemically satisfactory models provide valuable information which will hopefully simulate high resolution 2-D NMR/NOE studies in solution. PMID- 2322237 TI - Chemical synthesis of bovine transforming growth factor-alpha: synthesis, characterization and biological activity. AB - Bovine transforming growth factor-alpha (bTGF-alpha) is a 50 amino acid polypeptide with three disulfide linkages. In order to evaluate the biological function of this peptide, bTGF-alpha was synthesized via an automatic synthesizer and purified to homogeneity in high yield. The integrity of this synthetic peptide was confirmed by chemical analyses and bioassays. In a bovine liver radioreceptor assay, bTGF-alpha competes with radiolabeled EGF and has activity comparable to mEGF and hTGF-alpha. Compared to hEGF, bTGF-alpha elicits a greater response in a bovine mammary cell proliferation. PMID- 2322238 TI - The influence of angiotensin II on catecholamine synthesis in neuronal cultures from rat brain. AB - Incubation of primary neuronal cultures prepared from the hypothalamus and brainstem of neonatal rats with angiotensin II (Ang-II) resulted in a concentration-dependent effect on the incorporation of [3H]-tyrosine ([3H]-Tyr) into [3H]-catecholamines ([3H]-CA). At concentrations of 1 nM-1 microM, Ang-II (60 min. incubation) caused significant decreases (31-52%) in neuronal [3H]-CA content compared with controls. Conversely, higher concentrations of Ang-II (10 100 microM; 60 min.) caused significant increases (20-60%) in neuronal [3H]-CA content compared with controls. Both of these effects were blocked by co incubation with the Ang-II receptor antagonist Sar1Ile8-Ang-II. These observations demonstrate that neuronal cells in primary culture have the ability to synthesize [3H]-CA from [3H]-Tyr, and that Ang-II has a receptor-mediated biphasic influence on newly synthesized [3H]-CA (norepinephrine and dopamine). PMID- 2322239 TI - Niacin prevents DNA strand breakage by adenosine deaminase inhibitors. AB - The adenosine deaminase inhibitors deoxycoformycin and erythro-9-(2-hydroxy-3 nonyl) adenine (EHNA) induce single-strand DNA breaks in cultured human lymphocytes. Deoxycoformycin produced a significant number of strand breaks (4 fold increase compared to controls) and EHNA induced strand breaks in a dose dependent manner. Strand breaks stimulate repair by poly(ADP-ribosylation) which requires NAD+ as a cofactor. Niacin is a precursor of NAD+ and when preincubated with human lymphocytes prior to exposure to adenosine deaminase inhibitors, strand breakage was reduced significantly. The administration of niacin may represent an approach to decreasing the toxicity associated with these agents. PMID- 2322240 TI - Lysosomal tartrate sensitive acid phosphatase deficiency in cells which contain lysosomal "high uptake forms". AB - The catalytic and immunological properties of acid phosphatases (EC 3.1.3.2.) in different tissues were studied. It was demonstrated that high uptake forms of lysosomal enzymes like beta-galactosidase isolated from human platelets and bovine testis are mature enzymes, which have not lost their mannose-6phosphate marker. The results presented indicate that this phenomenon is related to a low activity or the complete absence of the lysosomal tartrate sensitive acid phosphatase activity in the tissues concerned. PMID- 2322242 TI - Presence of pancreatic trypsin inhibitor in adrenal medullary chromaffin cells. AB - A bovine pancreatic trypsin inhibitor was isolated from bovine adrenal medullary chromaffin granules. Its N-terminal sequence is: arg-pro-asp-phe-cys-leu-glu-pro pro-tyr-thr-gly-pro-cys-lys-ala-arg-ile- arg-tyr- phe-tyr-asn-ala-lys-ala-gly-leu cys-gln-thr-phe-val-tyr-gly-gly-cys-arg- ala-lys-arg-asn-asn-phe-lys- which corresponds precisely with the N-terminus of Bovine Pancreatic Trypsin inhibitor. The presence of this inhibitor in these granules suggests another method of regulating the prohormone proteases present there. PMID- 2322241 TI - Protein-mediated efflux of heme from isolated rat liver mitochondria. AB - Proteins are required for the efflux of heme from mitochondria and liposomes. The efflux from liposomes is independent of the heme-binding affinity of the protein (Biochem. 23:3715, 1984). We tested whether heme-binding proteins increase efflux of newly synthesized heme from structurally and functionally intact rat liver mitochondria. Mitochondria whose heme was labeled with 14C-delta-aminolevulinic acid, were incubated in the presence of glutathione transferases (GSTs), serum albumin (RSA) or heme-binding protein (HBP), all from the rat. HBP caused a 6-8 fold increase in efflux of newly synthesized heme as compared to that effected by RSA or GSTs. This result indicates that heme efflux from intact mitochondria, unlike that from liposomes, depends on the type of protein present and that HBP may specifically facilitate heme efflux from mitochondria. PMID- 2322243 TI - Quinone mediated ATP production in the filarial parasite Setaria digitata. AB - The cattle filarial parasite Setaria digitata, a facultative anaerobe which is reported to be cyanide insensitive, lacks cytochromes and presents many unique characters. Experiments showed the occurrence of two lower quinones Q6 and Q8 and its rapid synthesis is revealed by a [14C] acetate incorporation study. A schematic quinone mediated hydrogen peroxide production with the generation of ATP through oxidation of substrates has been proposed. Search for specific blockers at the level of quinone might prove to be an effective measure for the control of filarial parasites and thereby filariasis. PMID- 2322244 TI - Regulation of thyroid hormone binding to its cytosolic binding protein by L-alpha alanine. AB - The human cytosolic thyroid hormone binding protein (p58) was recently shown to be a monomer of pyruvate kinase, subtype PKM2, and have intrinsic pyruvate kinase activity. The present study evaluated the effect of L-alpha-alanine on the binding of 3,3',5-triiodo-L-thyronine (T3) and enzymatic activity of p58. Analysis of the competitive binding data indicated that alanine, at the physiological concentration, is a non-competitive inhibitor of T3 binding to p58. Furthermore, alanine was found to be a "mixed" inhibitor of the substrate phosphoenol pyruvate. However, binding of alanine to p58 did not block the association of p58 to form the tetrameric pyruvate kinase. PMID- 2322245 TI - Protection by acidotic pH and fructose against lethal injury to rat hepatocytes from mitochondrial inhibitors, ionophores and oxidant chemicals. AB - The importance of mitochondrial ATP formation and extracellular acidosis was evaluated in hepatocyte suspensions after different toxic treatments. Acidotic pH was protective against cell killing from all toxic treatments examined except for pronase, a toxic protease. Fructose, a substrate for glycolytic ATP formation, provided good protection against toxicity from cyanide, oligomycin, t-butyl hydroperoxide, menadione and cystamine. Protection by fructose against CCCP, gramicidin and Br-A23187 required oligomycin. This indicated that these ionophores were causing cytotoxicity by uncoupling oxidative phosphorylation. Fructose provided little protection against pronase and HgCl2, the latter compound being a potent inhibitor of glycolysis. In conclusion, disruption of mitochondrial ATP formation was a common event contributing to the toxicity of chemical oxidants and ionophores. Acidotic pH was generally protective under these conditions of impaired ATP generation. PMID- 2322246 TI - Isolation of immediate-early differentiation mRNAs by enzymatic amplification of subtracted cDNA from human endothelial cells. AB - The phenomena of cell growth and differentiation result from unique transcriptional programs. Inducible genes are therefore differentially expressed in response to various biochemical stimuli that regulate cell division and differentiation. To isolate differentially expressed mRNAs of unknown sequence, two techniques, differential and subtractive hybridization, have been used. Subtractive hybridization is superior for the isolation of rare mRNAs; however, its utility is somewhat limited by the fact that large amounts of driver mRNA are required for the procedure. We have used the polymerase chain reaction (PCR) to amplify minute quantities of unknown subtracted sequences, and thus, enhanced the sensitivity and ease of cloning differentially expressed mRNAs. We demonstrate the utility of this technique by describing the isolation of at least four unique cDNA clones of human endothelial cell mRNAs that are induced by the tumor promoter, phorbol ester, a factor that promotes immediate early events during the endothelial cell differentiation pathway in vitro. PMID- 2322247 TI - Marked decrease of mitochondrial DNA with multiple deletions in a patient with familial mitochondrial myopathy. AB - Muscle mitochondrial DNA (mtDNA) from a patient with mitochondrial myopathy was examined by Southern blotting. Her family history suggests autosomal dominant inheritance of this disorder. In contrast to other cases of this myopathy that are associated with a compensatory increase of mitochondria, in this patient, the content of mtDNA was markedly decreased (15% of controls), whereas protein of the ATP synthase beta-subunit was not decreased appreciably as judged by Western blotting. In addition, the mitochondrial DNA had multiple deletions, which were located between the replication origins of the heavy strand and light strand. PMID- 2322248 TI - Laminin surface binding sites and metastatic potential of 3LL tumor cells, increased by indomethacin. AB - The level of laminin receptor expression on tumor cell surface has been correlated with the capacity of tumor cells to metastasize. In the present work we show that indomethacin treatment of a low metastatic 3LL tumor cells increases the ability of these cells to form lung metastasis and the binding of [125I] laminin on their cell surface. Scatchard analysis showed that the incubation with indomethacin (10(-7) M) for 48 h induced a specific increase of laminin binding sites on 3LL cell surface (1.5 fold per cell), presenting both a high and low affinity class of binding sites. On the other hand, indomethacin treatment (2 mg/kg weight) of tumor bearing mice increased the number of spontaneous metastatic nodules on the lung surface. Likewise, when 3LL tumor cells were incubated with indomethacin (10(-7) M) for 48 h, we observed an enhancement of lung metastatic nodules after intravenous injection of tumor cells. This last effect was partially reversed by peptides DPGYIGSR or YIGSR, corresponding to the active site at the B1 chain of laminin, with ability to bind the 67-kD laminin cell surface receptors. In summary, our results show that the increased attachment of 3LL tumor cells to laminin mediated by indomethacin is directly correlated with the metastatic activity of these cells, and suggests that the indomethacin effect on the metastatic potential could involve a modulation of laminin receptors on tumor cell surface. PMID- 2322249 TI - High-resolution solid-state nuclear magnetic resonance spectra of dentin collagen. AB - Insoluble collagen of bovine dentin was characterized by high-resolution solid state 13C nuclear magnetic resonance (NMR) spectroscopy using a cross polarization magic angle spinning procedure. A downfield shift was observed in the signal of hydroxyproline C beta compared with that in skin collagen, indicating a distortion in the hydroxyproline structure. A signal of 31P NMR was detected in dentin collagen that was compatible with the presence of matrix associated phosphoprotein. PMID- 2322250 TI - Codon usage pattern in alpha 2(I) chain domain of chicken type I collagen and its implications for the secondary structure of the mRNA and the synthesis pauses of the collagen. AB - A stability map of local secondary structure of the mRNA of the triple-helical alpha 2(I) chain domain of chicken type I collagen was obtained by plotting the free energy of the optimal secondary structure of a local segment in mRNA against the segment position along a base sequence of the mRNA. It was found that the positions of the minima of free energy in the plot coincide with the positions where synthesis pauses of the alpha-chain polypeptides of the corresponding sizes translated from the mRNA have been reported to occur (1). The codon usage pattern of each of the three major amino acids of the alpha-chain domain of the collagen, Gly, Pro and Ala, fluctuates considerably along the base sequence segments of the mRNA and a deviation of the pattern from that of the average of the whole alpha 2(I) chain domain mRNA, particularly for Gly codons, leads to a loss of the stability of the local secondary structure of the mRNA. The results suggest that selection has operated on the codon usage to optimize the secondary structure characteristic of the mRNA of the chicken collagen alpha 2(I) chain domain which leads to a nonuniform polypeptide elongation pattern. PMID- 2322251 TI - A novel cardio-excitatory peptide isolated from the atria of the African giant snail, Achatina fulica. AB - An undecapeptide which potentiates the beat of the ventricle in the African giant snail, Achatina fulica Ferussac, was purified from the atria of the snail. Its primary structure was determined to be H-Ser-Gly-Gln-Ser-Trp-Arg-Pro-Gln-Gly-Arg Phe-NH2. This peptide was found to have excitatory actions not only on the ventricle but also on the penis retractor muscle, the buccal muscle and the identified neurons controlling the buccal muscle movement of Achatina. PMID- 2322252 TI - Expression of the brown fat mitochondria uncoupling protein in Xenopus oocytes and important into mitochondrial membrane. AB - Non shivering thermogenesis of brown adipose tissue is due to the uncoupling protein (UCP), located in the inner mitochondrial membrane, which functions as a proton translocator and can thus uncouple mitochondrial respiration. We describe here the expression of UCP in Xenopus laevis oocytes after injection of UCP mRNA, which was transcribed in vitro. UCP seems to be correctly transported into mitochondria and integrated into the membrane, but we were not able to establish definitely the functionality of this UCP. We conclude that this expression system could be suitable for the study of the mitochondrial import mechanism but not for the examination of physiological properties of UCP. PMID- 2322253 TI - Intracellular calcium in the control of osteoclast function. II. Paradoxical elevation of cytosolic free calcium by verapamil. AB - We report here for the first time that verapamil elevates cytosolic calcium. We have found that in the isolated rat osteoclast, verapamil at low micromolar concentrations did not block the elevation of cytosolic free calcium ([Ca++]i) in response to elevated extracellular calcium concentrations ([Ca++]e). However, high micromolar concentrations of verapamil (300 microM or above) led to a rapid sustained elevation of [Ca++]i. These concentrations of verapamil had effects on osteoclast morphology and resorptive activity that were similar to those produced by elevated [Ca++]e: there was a marked dose-dependent fall in cell spread area and osteoclastic bone resorption. The sensitivity of osteoclasts to high micromolar concentrations of verapamil is unique and could not be mimicked in macrophages and lymphocytes. PMID- 2322254 TI - Identification of a novel inositol phosphate recognition site: specific [3H]inositol hexakisphosphate binding to brain regions and cerebellar membranes. AB - [3H]Inositol hexakisphosphate (InsP6) binds with a heterogeneous distribution to frozen sections of unfixed rat brain and is displaced by unlabelled InsP6. The pattern of binding correlates with binding to neuronal cell bodies. [3H]InsP6 binding to cerebellar membranes has been further characterised, is reversible, and saturable, and exhibits high specificity for inositol polyphosphates. The IC50 for competition by unlabelled InsP6 is approximately 100nM, whereas inositol 1,3,4,5,6 pentakisphosphate (Ins(13456)P5), inositol 1,3,4,5 tetrakisphosphate (Ins(1345)P4), and inositol 1,4,5 trisphosphate (Ins(145)P3) bind with an affinity at least one order of magnitude lower. [3H]InsP6 binding is clearly distinct from previously characterised Ins(145)P3 (ref. 1, 2) and Ins(1345)P4 (ref. 3) binding, both in terms of pharmacology and brain distribution. PMID- 2322255 TI - Inhibition of human neutrophil activation by the allergic mediator release inhibitor, CI-949: mechanism of inhibitory activity. AB - CI-949 [5-methyl-3-(1-methylethoxy)-1-phenyl-N-1H-tetrazol-5-yl-1H- indole-2- carboxamide, L-arginine salt] inhibits human neutrophil activation in response to stimuli which promote calcium mobilization or calcium influx. This report further examines the effect of CI-949 on phosphoinositide-dependent stimulus-response coupling. At 100 microM, CI-949 had no inhibitory effect on human neutrophil phospholipase C or protein kinase C. In contrast, CI-949 inhibited FMLP stimulated intracellular calcium mobilization with an IC50 of 8.4 microM. The compound was also a potent calmodulin antagonist, inhibiting calmodulin-dependent phosphodiesterase activity with an IC50 of 31.0 microM. The calmodulin antagonist activity of CI-949 was confirmed by fluorescence spectroscopy. These results demonstrate that CI-949 may function through inhibition of calcium- and calmodulin-dependent signal transduction processes. PMID- 2322256 TI - Characterization of low populated peptide helical structures in solution by means of NMR proton conformational shifts. AB - A NOE independent NMR method is proposed to characterize unambiguously residues involved in low populated isolated peptide helices. The method is based on the comparison of amide and H alpha chemical shift changes originated upon the addition of stabilizing or denaturing agents with true helical conformational shifts that have been measured for the first time using an isolated model peptide helix, the one formed by Ac-(Leu-Lys-Lys-Leu)3-NHEt in aqueous solution. PMID- 2322257 TI - Endothelial cells metabolize NG-monomethyl-L-arginine to L-citrulline and subsequently to L-arginine. AB - NG-monomethyl-L-arginine (MeArg) inhibits the release of endothelium-derived relaxing factor (EDRF) from endothelial cells (EC) and the formation of nitric oxide (NO) from L-arginine (Arg) in EC and activated macrophages. We have compared the inhibitory potency of MeArg to that of N omega-nitro-L-arginine (NO2Arg), a more potent inhibitor of EDRF synthesis in vitro. NO2Arg (100 microM) was significantly more potent than MeArg in inhibiting the endothelium-dependent relaxation of rabbit aorta induced by acetylcholine. MeArg and NO2Arg (10 and 30 microM) also inhibited the release of EDRF from bovine aortic cultured EC. In the anaesthetized rat in vivo, the pressor effect of NO2Arg (3 and 10 mg kg-1) was significantly larger and longer lasting than that of MeArg. These differences in potency could be due to the extensive metabolism of MeArg but not NO2Arg to L citrulline (Cit) and subsequently to Arg by EC. The enzyme responsible for the conversion of MeArg to Cit had the characteristics of a novel deiminase, NG,NG dimethylarginine dimethylaminohydrolase, recently isolated from rat kidney. PMID- 2322258 TI - Transfection of cDNA with G----T point mutation at the cleavage site of insulin receptors to COS 7 cells. AB - To study whether the G----T point mutation of insulin proreceptors at the cleavage site which changed -Arg-Lys-Arg-Arg- to -Arg-Lys-Arg-Ser- caused unprocessed insulin receptors with decreased insulin binding affinity, we performed transfection of cDNA with the mutation in COS 7 cells and examined the expressed insulin receptors. After site-directed mutagenesis, an expression vector pGEM3SV was used to make a plasmid which contained full-length HIRcDNA behind SV40 early promoter. Transfection of normal HIR cDNA produced normal insulin receptors on the plasma membranes in COS 7 cells. However, transfection of cDNA with the mutation resulted in the presence of 210K proreceptors in the plasma membranes with decreased insulin binding ability (35% of normal). These results suggest that the mutation, not the defect of converting enzyme, was the cause for unprocessed insulin proreceptors in the patients with insulin resistance. PMID- 2322259 TI - Characterization and regulation of a cDNA clone for rat pancreastatin. AB - Pancreastatin is a recently isolated pancreatic peptide which has been shown to be a potent inhibitor of insulin release in a perfused rat pancreas assay (1). In order to study the regulation of pancreastatin mRNA and to examine the primary structure of its precursor, genomic and cDNA clones corresponding to pancreastatin have been isolated from rat genomic and pancreatic libraries. The number of genes isolated, along with southern blot analyses, suggested that pancreastatin may be part of a gene family. We examined the regulation of pancreastatin expression by insulin and streptozotocin treatment. Pancreastin mRNA levels in rats are altered in response to insulin and streptozotocin. PMID- 2322260 TI - Divergent effects of filamin and tropomyosin on actin filaments bundling. AB - Filamin increases and tropomyosin decreases the susceptibility of F-actin to form bundles of filaments in the presence of polyethylene glycol 6000. The two proteins, which are located in the leading edge and in the internal part of the cell, respectively, are thus likely to display divergent effects on the microfilaments into bundles transition in these two areas of the cell. PMID- 2322261 TI - Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography. AB - A part of low density lipoproteins (LDL) isolated from the blood of healthy subjects and patients with coronary atherosclerosis bind to a Sepharose-linked Ricinus communis agglutinin, a lectin that interacts specifically with galactose residues. Bound LDL can be replaced by galactose, but not other saccharide constituents of the LDL molecule (mannose, glucose, N-acetylglucosamine, sialic acid). Bound LDL subfraction has a 2-3-fold lower content of sialic acid as compared with unbound LDL. The blood content of desialylated LDL in atherosclerotic patients was about 3-fold higher (1.5- to 6-fold) than in healthy subjects. Desialylated LDL induced a 2- to 4-fold more intensive accumulation of total cholesterol in cultured human aortic intimal cells. Unbound LDL had no effect on intracellular deposition of lipids. It is suggested that the subfraction of desialylated LDL may be responsible for the atherogenicity of LDL isolated from blood of atherosclerotic patients. PMID- 2322262 TI - Parathyroid hormone related peptide can function as an autocrine growth factor in human renal cell carcinoma. AB - Parathyroid hormone related peptide (PTHrP) has been implicated in the cause of the hypercalcemia associated with a number of malignant tumours. The data presented here suggests that PTHrP (in addition to its known role of mediating hypercalcemia) may be involved in the autocrine regulation of growth of some tumours. Polyclonal PTHrP antiserum almost totally inhibited the growth of a human renal cell carcinoma cell line, known to secrete PTHrP, in vitro and growth was significantly inhibited by the competitive PTH antagonist PTH (3-34)NH2. PMID- 2322263 TI - Evidence for cooperative binding of chlorpromazine with hemoglobin: equilibrium dialysis, fluorescence quenching and oxygen release study. AB - Binding of chlorpromazine (CPZ) with human hemoglobin has been studied by equilibrium dialysis and fluorescence quenching. Results of equilibrium dialysis experiment when analysed by Hill plot revealed that the binding was positively cooperative with overall affinity constant K = 3.8 x 10(3) M-1. CPZ quenched the fluorescence of hemoglobin and the analysis of the quenching data by Stern-Volmer equation indicated two types of quenching process, namely, dynamic and static quenching. Dynamic quenching constant was measured from the decay of fluorescent life time of tryptophans of hemoglobin in presence of CPZ. Static quenching constant concerned with the ground state complex formation between CPZ and hemoglobin was found to be 5 x 10(3) M-1. Almost all the tryptophans of hemoglobin were found to be accessible for CPZ to interact with. Oxygen was found to be released when CPZ was added to hemoglobin. Extent of release of oxygen depends on the D/P ratio of CPZ(D): hemoglobin(P). PMID- 2322264 TI - Chemotactic activity for human PMN generated during ethanol metabolism by rat hepatocytes: role of glutathione and glutathione peroxidase. AB - Infiltration of the liver by polymorphonuclear leukocytes is a characteristic feature of alcoholic hepatitis. We have previously shown that liver cytosol metabolizing ethanol generates chemoattractant activity for polymorphonuclear leukocytes and that hydroxyl radical scavengers inhibit this process. To investigate the possibility that endogenous glutathione and glutathione peroxidase also inhibit this process, we evaluated chemoattractant activity production by glutathione and glutathione peroxidase deficient rat liver cytosol during ethanol metabolism. Incubation of cytosol deficient in both glutathione and glutathione peroxidase with 10 mM ethanol for 1 hour resulted in a 500-fold increase in chemoattractant activity when compared to cytosol with normal glutathione and glutathione peroxidase content. These findings provide further evidence for a role of oxygen free radicals in the generation of chemotactic activity and they also suggest that the ethanol-induced decrease in hepatic glutathione and glutathione peroxidase reported by others may have a significant potentiating effect on the recruitment of pro-inflammatory cells into the liver. PMID- 2322265 TI - Cloning and nucleotide sequence analysis of the human beta-microseminoprotein gene. AB - Beta-microseminoprotein (MSP) is a small protein (94 amino acids) synthesized by the epithelial cells of the prostate gland and secreted into the seminal plasma. Restriction endonuclease mapping of human genomic DNA with a human MSP cDNA probe identified a 19 kilobase (Kb) hybridizing band in both EcoRI and BamHI digestions. Subsequently, the 19 Kb EcoRI fragment of human genomic DNA containing the MSP gene was isolated and cloned into an EMBL4 phage vector. Screening of the recombinant phages resulted in the isolation of one clone containing the MSP gene. Restriction endonuclease mapping and sequence analysis of this clone revealed the human MSP gene of approximately 15 Kb in length. The gene contains four exons and three large introns of approximately 6, 1, and 7 Kb. PMID- 2322267 TI - Extremely high levels of NADPH in guinea pig lens: correlation with zeta crystallin concentration. AB - Zeta-crystallin, a major "taxon-specific" protein of the guinea pig lens, specifically binds NADPH. Analysis of pyridine nucleotide levels in guinea pig lens revealed values for NADPH approximately 50-fold higher than in other lenses. Indeed to our knowledge the values reported are higher than have been observed in any tissue. A clear correlation exists between NADPH and zeta-crystallin contents of the lens both in normal guinea pigs during development and in a line of guinea pigs with a mutation in the gene for zeta-crystallin. Heterozygotes for this mutation had a 50% reduction in NADPH, while homozygotes have only about 6% of the normal level. NADP+ levels were also markedly elevated suggesting that redox cycling of the NADPH is occurring. PMID- 2322266 TI - Effect of angiotensin II and III on inositol polyphosphate production in differentiated NG108-15 hybrid cells. AB - Neuroblastoma x glioma hybrid cells (NG108-15), differentiated by treatment with 1.5% dimethyl sulfoxide (DMSO) and 0.5% fetal bovine serum, were used to measure the effect of angiotensin II and III (ANG II and ANG III) on the generation of inositol polyphosphates. ANG II increased the synthesis of inositol monophosphates (IP1), inositol diphosphates (IP2), and inositol trisphosphates (IP3) with maximal responses observed at 300, 120, and 30 sec, respectively. The percent increases above basal values at the maximal responses were 140% +/- 9% (IP1), 142% +/- 4% (IP2), and 132% +/- 4% (IP3). This effect was not attenuated by pretreatment of the cells with pertussis toxin. Furthermore, both ANG II and ANG III increased the production of inositol polyphosphates in a dose-dependent manner with ED50 values of 145 nM and 11 nM, respectively. We conclude that differentiated NG108-15 cells express an ANG III selective receptor that mediates phosphatidylinositol breakdown through a pertussis toxin insensitive G-protein. PMID- 2322268 TI - A specific beta gamma-subunit of transducin stimulates ADP-ribosylation of the alpha-subunit by pertussis toxin. AB - Transducin (T alpha and T beta gamma) is a GTP-binding protein involved in the visual transduction process in a rod outer segment. We have previously demonstrated that T beta gamma is a mixture composed of two components, T beta gamma-1 and T beta gamma-2, with distinctive gamma-subunits, T gamma-1 and T gamma-2, respectively (Fukada et al., 1989, J. Biol. Chem., 264, 5937-5943). To investigate the interaction between T alpha and the two components of T beta gamma, the effect of either T beta gamma-1 or T beta gamma-2 on the ADP ribosylation of T alpha catalyzed by pertussis toxin (IAP) was examined. T beta gamma-2 stimulated the ADP-ribosylation of T alpha by IAP, while T beta gamma-1 displayed almost no enhancement of the ADP-ribosylation. Addition of T beta gamma 1 to the mixture of T alpha and T beta gamma-2 had no effect on the ADP ribosylation of T alpha. These results indicate that T alpha and T beta gamma-2 form a complex that serves as a substrate of IAP in the ADP-ribosylation reaction, while T beta gamma-1 has a little affinity for T alpha. It was suggested that T gamma-2 is an essential subunit for T beta to interact with T alpha. PMID- 2322269 TI - Smooth muscle myosin light chain kinase: rapid purification by anion exchange high-performance liquid chromatography. AB - A rapid procedure for the purification of myosin light chain kinase present in chicken gizzard smooth muscle using anion exchange high-performance liquid chromatography is described. The procedure allows preparation of microgram amounts of the protein directly from the extract of gizzard myofibrils and then is suitable for the study of myosin light chain kinase in small muscles. The protein was judged to be greater than 95% pure by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The enzyme retains its activity since it catalyzes the calcium-calmodulin-dependent phosphorylation of the 20,000-Da myosin light chain. PMID- 2322270 TI - Aminopeptidase in human CSF which degrades delta-sleep inducing peptide (DSIP). AB - This study describes the purification and characterization of an aminopeptidase from human cerebrospinal fluid capable of degrading delta-sleep-inducing-peptide (DSIP). The enzyme has an apparent molecular weight of approximately 80,000 dalton. It is sensitive towards amastatin, bestatin and EDTA and is optimally active at neutral pH. The recovered enzyme was also found to degrade other neuropeptides, e.g., the enkephalins. PMID- 2322271 TI - A smaller initial dose protects mice against several lethal doses of ammonium acetate. AB - The synthesis of urea in the liver is the main mechanism for the elimination of excess ammonia. Rapid stimulation of the synthesis of urea (e.g. by administration of carbamyl glutamate, the analog of the physiological activator of carbamyl phosphate synthetase I) protects animals given lethal doses of ammonia. Since ammonia enhances the activity of the urea cycle, we tested and show here that administration of small doses of ammonium acetate supresses the mortality induced by a series of repeated LD100 of ammonium acetate separated by one hour, when the first LD100 is injected i.p. starting from 30 min to 5 hours after the initial smaller dose of ammonium acetate. Under these conditions, the levels of ammonia in blood are elevated more than ten times, but in spite of the greater amount of ammonia administered, the ammonemia is much lower than in mice dying after a single LD100. The enhanced synthesis of urea observed is correlated with an increase in the intramitochondrial content of N-acetyl glutamate. These findings are of interest as far as the short-term regulation of urea cycle, the mechanism of ammonia toxicity and have clinical implications. PMID- 2322272 TI - The steroid antagonist RU38486 is metabolized by the liver microsomal P450 mono oxygenases. AB - Microsomal preparations from adult male rat liver actively oxidized RU38486 into the 11 beta-monodemethylated, 11 beta-didemethylated and 17 alpha-hydroxylated derivatives, metabolites which are known to be formed in vivo. These oxidative reactions were inhibited at different degrees by P450 chemical inhibitors. Pretreatment of the animals by P450 mono-oxygenase prototype inducers led to drastic changes in RU38486 metabolization. Methylcholanthrene treatment carried out a significant decrease while phenobarbital markedly increased the metabolic activity of the liver microsomes. Moreover, antibodies to methylcholantrene inducible P450 forms did not affect the metabolic activity while a complete blockade-of RU38486 oxidation was observed in the presence of antibodies to phenobarbital- inducible forms. The present results demonstrate that liver P450 mono-oxygenases are engaged in different oxidative steps of RU38486 metabolism and that phenobarbital-inducible but not methylcholanthrene-inducible P450 forms are active in RU38486 degradation. PMID- 2322273 TI - Transcriptional regulation of ferritin heavy chain messenger RNA expression by thyroid hormone. AB - The effect of 3,5,3'-triiodo-L-thyronine (T3) on the steady state levels of ferritin heavy chain (ferritin H) mRNA in cultured rat glioma C6 cells and various rat tissues was examined. Addition of T3 to cultured C6 cells showed the time and dose-dependent increase in the steady-state level of ferritin H mRNA. In vitro nuclear run-on assay revealed that the stimulatory effect was due to the increase in the transcription rate of ferritin H gene. T3 had no effect on the half life of ferritin H mRNA. In hyperthyroid rats, the level of ferritin H mRNA in the kidney was elevated. On the contrary, that was decreased in hypothyroid rats. The results suggest the involvement of T3 in the regulation of ferritin H gene expression. PMID- 2322275 TI - Decapitation-induced changes in inositol phosphates in rat brain. AB - Decapitation resulted in a time-dependent production of inositol phosphates in rat brain. This production was analyzed by measuring both the radioactivity and the concentrations of inositol phosphates generated from [3H]inositol-labeled phospholipids. Both measurements produced the same time-dependent changes, including a rapid decrease in inositol 1,4,5-trisphosphate within 1.5 min, a 6 fold increase in inositol 1,4-bisphosphate to a maximum at 1.5 min, a 5-fold rise in inositol 4-monophosphate to a maximum at 2.5 min, and little change in inositol 1-monophosphate. The temporal changes in the mass and radioactivity of these compounds, together with the decrease in labeling of phosphatidylinositol 4,5-bisphosphates, support the idea that the inositol phosphates originate from the hydrolysis of phosphatidylinositol 4,5-bisphosphates and not from either the direct hydrolysis of phosphatidylinositol 4-phosphates or phosphatidylinositols. PMID- 2322274 TI - Partial nucleotide sequence of the parvalbumin from chicken thymus designated "avian thymic hormone". AB - The incomplete amino acid sequence of the protein identified as avian thymic hormone was recently reported [Brewer et al. (1989), Biochem. Biophys. Res. Commun. 160, 11555-1161], and a very high degree of homology to the parvalbumins was apparent. Using mixed oligonucleotide primers based on the reported protein sequence, we have succeeded in amplifying and cloning a 188 bp fragment of the coding region for this protein, beginning with double-stranded cDNA prepared from chicken thymus mRNA. The translated nucleotide sequence of this fragment and the reported amino acid sequence display substantial disagreement. Most notably, the nucleotide sequence indicates that the CD site of avian thymic hormone is a typical parvalbumin CD site. PMID- 2322276 TI - The non-phorbol ester tumor promoter okadaic acid does not promote morphological transformation or inhibit junctional communication in hamster embryo cells. AB - Okadaic acid is a potent non-phorbol ester mouse skin tumor promoter. Unlike the phorbol ester tumor promoters, okadaic acid is unable to promote the induction of morphological transformation in Syrian hamster embryo cell colonies. On the contrary, okadaic acid seems to counteract the effect of phorbol esters on transformation. Also unlike phorbol ester tumor promoters, okadaic acid does not inhibit intercellular communication, neither in primary hamster embryo cells, nor in the phorbol ester sensitive cell line BPNi. Furthermore, okadaic acid has no effect on the reoccurrence of communication following removal of 12-O tetradecanoylphorbol-13-acetate. PMID- 2322277 TI - Monoclonal antibodies against human synovial phospholipase A2. AB - Four monoclonal antibodies (HP-1, HP-2, HP-3 and HP-4) with differing reactivities were raised against human synovial fluid phospholipase A2. None of them bound to exocrine phospholipases A2, such as those from pancreas or snake venom. However, antibodies HP-1 and HP-3 showed cross-reactivity with rabbit and rat platelet secretory phospholipases A2, which share common enzymatic and structural features with the human synovial enzyme. Antibodies HP-1, HP-2 and HP 3 inhibited the activity of human synovial phospholipase A2. The antibodies were used to develop a rapid immunoaffinity column chromatographic procedure for enzyme purification. In some preparations, the recovery of total activity after immunoaffinity column chromatography was more than 100% suggesting the existence of endogenous inhibitory factors of phospholipase A2 in human synovial fluid. PMID- 2322278 TI - Functional expression of human leukocyte elastase (HLE)/medullasin in eukaryotic cells. AB - We have cloned a full length cDNA for human leukocyte elastase (HLE, EC 3.4.21.37)/medullasin from the cDNA library of human leukemic cell line, ML3. Recombinant plasmid for the expression of HLE cDNA in eukaryotic cells was constructed in which HLE cDNA was fused in a frame to a leader sequence of human interleukin-2 (IL-2). COS-1 cells, transfected with the plasmid, secreted fusion protein consists of N-terminal 8 amino acid (aa) residues of human IL-2 and 238 aa residues of HLE. As the fusion protein was designed to be connected through lysine residue, elastase activity was generated after digestion of the fusion protein with lysyl-endopeptidase. PMID- 2322279 TI - The primary structure of rat ribosomal protein L35. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L35 was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed from the NH2 terminal amino acid sequence of the protein. Ribosomal protein L35 has 122 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has a molecular weight of 14,412. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 15-17 copies of the L35 gene. The mRNA for the protein is about 570 nucleotides in length. Rat L35 is related to the archaebacterial ribosomal proteins Halobacterium marismortui L33 and Halobacterium halobium L29E; it is also related to Escherichia coli L29 and to other members of the prokaryotic ribosomal protein L29 family. The protein contains a possible internal duplication of 11 residues. PMID- 2322280 TI - Protein-ligand interactions: interaction of nitrosamines with nicotinic acetylcholine receptor. AB - Fluorimetry and spectrophotometry have been used to study the binding of dimethyl, dipropyl, dibutyl and diphenylnitrosamine to nicotinic acetylcholine receptor isolated, and purified, from Torpedo fuscomaculata. Scatchard analysis indicates that all four ligands are true agonists of the receptor exhibiting positive cooperative binding with the existence of more than one class of binding site. The number of binding sites for the nitrosamines approximates 2. Diphenylnitrosamine binds to the receptor more tightly at low concentrations (Kd1 = 1.3 microM) than the aliphatic nitrosamine (Kd1 = 8-12 microM). Yet at high concentrations all nitrosamines behaved with similar Kd values (27-38 microM). PMID- 2322281 TI - Purification of a calcium binding protein (rat SPARC) from primary Sertoli cell enriched culture medium. AB - A protein with an apparent Mr of 43,000 was purified from Sertoli cell-enriched culture medium by sequential anion-exchange, gel permeation, C4 reversed-phase, and diphenyl reversed-phase HPLC. N-Terminal sequence analysis of this protein revealed a sequence of NH2-XPQTEAAEEMVAEETVV for the first 17 amino acids. Comparison of this sequence with existing protein data base maintained at the Protein Identification Resource revealed that it shares extensive identity with a previously described protein secreted by mouse embryo parietal endoderm, SPARC, which is equivalent to a protein secreted by a basement-membrane-producing tumor, BM-40; and a bone protein, osteonectin. This protein also possesses similar in vitro biological activity of SPARC in which it binds Ca2+. The possible physiological significance of this protein was discussed. PMID- 2322282 TI - Cytosolic free magnesium in cardiac myocytes: identification of a Mg2+ influx pathway. AB - Regulation of intracellular Mg2+ activity in the heart is not well characterized. Cardiac myocytes were prepared as primary cultures from 7 day old chick embryo hearts and intracellular Mg2+ concentration [( Mg2+]i) was determined in single ventricular cells with mag-fura-2. Basal [Mg2+]i was 0.48 +/- 0.03 mM in normal culture medium. There was no correlation of basal [Mg2+]i with cellular contraction or intracellular [Ca2+]i (determined with fura-2). Cardiocytes cultured (16 hr) in low Mg (0.16 mM) media contained 0.21 +/- 0.05 mM Mg2+ which returned to normal levels when placed in Mg media with a refill time of 20 min. Basal [Ca2+]i (121 +/- 11 nM) and stimulated [Ca2+]i (231 +/- 41 nM) was similar to control cells. Verapamil, 25 microM, reversibly blocked Mg2+ refill. In conclusion, the basal [Mg2+]i of isolated cardiomyocytes is considerably below the Mg2+ electrochemical equilibrium allowing passive Mg2+ influx. The influx pathway for Mg2+ is inhibited by verapamil and appears to be independent of Ca2+ as assessed by fura-2. PMID- 2322283 TI - Site-directed mutagenesis of mouse thymidylate synthase: alteration of Arg44 to Val44 in a conserved loop guarding the active site has striking effects on catalysis and nucleotide binding. AB - The arginine located at position 44 of mouse thymidylate synthase is in a highly conserved loop that is in close proximity to the active site cleft of the enzyme. Structural analyses have suggested that this arginine forms hydrogen bonds with the alpha-carboxylate of the C-terminal amino acid and the phosphate of the substrate analog, FdUMP (D. A. Matthews, K. Appelt and S. J. Oatley, (1989) Adv. Enz. Reg., 29, 47-60). We have used protein engineering techniques to change this amino acid residue to valine. This alteration leads to large reductions in the ability of the enzyme to form covalent complexes with substrate (dUMP) or inhibitor (FdUMP) and at least a 100-fold reduction in catalytic activity. These observations show that this arginine plays an important role in maintaining catalytic activity of the enzyme. PMID- 2322284 TI - Carbon catabolite regulation of phenylacetyl-CoA ligase from Pseudomonas putida. AB - Phenylacetyl-CoA ligase (PA-CoA ligase) from P. putida U is a newly described enzyme involved in the aerobic catabolism of phenylacetic acid. The enzyme was specifically induced when P. putida was grown in a chemically defined medium containing phenylacetic acid as the sole carbon source. The induction of PA-CoA ligase was delayed by adding easily metabolizable carbon sources to the medium; the effect was more drastic in the presence of glucose. Glucose did not cause catabolic inactivation but rather catabolic repression, this effect being reversed by cAMP. PMID- 2322285 TI - Tissue inhibitor of metalloproteases (TIMP) is matrix associated in aortic tissue: report of a radioimmunoassay. AB - Tissue inhibitor of metalloproteinases (TIMP) is the major inhibitor of collagenase, gelatinase, proteoglycanase, stromelysin, and metalloelastases. An imbalance between proteases and inhibitors has been implicated in numerous disease processes including tumor invasion, rheumatoid arthritis, emphysema, and aortic aneurysm disease. The purpose of this investigation was to develop a polyclonal antibody to recombinant TIMP and establish an immunoassay to measure immunoreactive protein in normal and diseased tissues. A polyclonal antibody was produced in rabbit against recombinant human TIMP which was characterized and used to establish a radioimmunoassay. The assay was used to measure immunoreactive protein in fibroblast conditioned medium, human serum, and aortic extracts. There was more immunoreactive TIMP in matrix associated urea extracts than soluble salt extracts from human aorta, suggesting that TIMP is matrix associated. The sensitivity of the assay enables the specific measurement of this inhibitor in serum, fibroblast culture medium, and tissue extracts. PMID- 2322286 TI - Identification of the monocyte chemotactic protein from human osteosarcoma cells and monocytes: detection of a novel N-terminally processed form. AB - The chemotactic activity for monocytes in culture supernatants from double stranded RNA-stimulated human MG-63 osteosarcoma cells and from LPS-stimulated human monocytes was purified to homogeneity and characterized by amino acid sequence analysis. The chemotactic protein derived from the fibroblastoid osteosarcoma cells had a blocked N-terminus but sequencing of tryptic fragments showed that it was identical with a recently identified monocyte chemoattractant designated MCP-1 or MCAF isolated from glioma or myelomonocytic cells, respectively. Preparations of monocyte -derived chemotactic activity appeared to contain not only the blocked protein, but also a novel N-terminally processed form of this molecule, lacking 5 amino acid residues. PMID- 2322287 TI - Effect of 14,15-epoxyeicosatrienoic acid infusion on blood pressure in normal and hypertensive rats. AB - Intravenous (IV) and intraarterial (IA) infusion of 14,15-epoxyeicosatrienoic acid (14,15-EET) produced a dose-dependent decrease in mean arterial blood pressure (MAP) in normal and spontaneously hypertensive rats (SHR). The hypotensive effect of 14,15-EET was observed from 1 microgram/kg to 10 micrograms/kg with a maximum reduction in MAP as much as 45 +/- 6 mmHg in both normal and SHR. In normal rats the hypotensive effect was found to be more pronounced when 14,15-EET was infused IA than IV. This suggests that 14,15-EET may be metabolized as it passes through the lungs. However, in SHR there was no difference in MAP when 14,15-EET was infused either IA or IV. This indicates that there is a differential removal of the epoxide across the pulmonary circulation. Administration of indomethacin failed to inhibit the hypotensive action of 14,15 EET, suggesting that it may not be a cyclo-oxygenase dependent mechanism. However, the PAF antagonist of BN-52021 inhibited the hypotensive action of 14,15 EET. This therefore, suggests that the release of PAF may be involved in the hypotensive action of this epoxide of arachidonic acid. PMID- 2322288 TI - Isolation, purification and characterization of beta-hCGRP from human spinal cord. AB - Human beta-calcitonin gene-related peptide (beta-hCGRP) was isolated and purified from spinal cord. The complete characterization of this material was based on definitive mass analysis by fast atom bombardment mass spectrometry together with gas phase sequencing. Combining these data we have characterized the structure of beta-hCGRP including the C-terminal sequence, the presence of the S-S bridge and of phenylalanineamide as the C-terminal amino acid, and fully confirmed the amino acid sequence predicted from the nucleotide analysis. PMID- 2322289 TI - Facilitated uptake of zinc into human erythrocytes. Relevance to the treatment of sickle-cell anaemia. AB - The ability of a number of heterocyclic metal chelators to deliver zinc into red cells, to release the liganded zinc to haemoglobin and thereby cause a left shift in the oxygen dissociation curve of intact red cells has been investigated. Incubation of neutrally charged zinc-pyrone and zinc-pyridin-2-one complexes with red cells led to the rapid accumulation of zinc within cells, whereas unliganded zinc in the form of zinc acetate, zinc chloride or zinc sulphate accumulated only slowly. The rate at which zinc was delivered to red cells by pyrone and pyridin-2 one ligands increased with increasing lipid solubility of the ligands. The uptake of zinc into both normal adult and sickle red cells was associated with a dose dependent increase in the oxygen affinity of haemoglobin. The degree of left shift in the oxygen dissociation curve following the incubation of red cells with zinc-pyrone and -pyridin-2-one complexes suggests that these complexes may find application as agents to increase the oxygen affinity of haemoglobin in sickle cell disease and thereby decrease the probability of intravascular sickling at low tissue oxygen tensions. Ethylmaltol appears to be a particularly useful agent due to its known low toxicity. PMID- 2322290 TI - The autoradiographic localization of adenylate cyclase in rat kidney using [3H]forskolin. AB - The localization of [3H]forskolin binding to microscope slide mounted sections of rat kidney has been examined using autoradiography. Saturation studies showed [3H]forskolin binding to two sites, a high affinity site (KD = 8.7 nM, Bmax = 0.14 pmol/mg protein) and a low affinity site (KD = 6.7 microM, Bmax = 11.0 pmol/mg protein). Autoradiographs showed high affinity binding (thought to identify stimulatory guanine nucleotide binding protein (Gs)-linked adenylate cyclase) to all renal structures known to possess hormone sensitive adenylate cyclase, including all tubular segments, glomeruli and blood vessels. High concentrations of binding were associated with a portion of the proximal tubule and with papillary collecting tubules and ducts. PMID- 2322291 TI - Two pathways for biliary copper excretion in the rat. The role of glutathione. AB - To evaluate the role of glutathione in biliary copper excretion, we studied this process in control Wistar rats and in mutant Wistar rats (GY rats), in which the secretion of glutathione into bile is deficient. For comparison, biliary zinc excretion was determined simultaneously. In spite of the markedly reduced bile flow (-45%) in GY rats, biliary output rates of endogenous copper were virtually identical in GY and control rats. In contrast, zinc output was drastically reduced in GY rats compared to controls (-80%). Biliary excretion patterns after intravenous administration of copper, in doses ranging from 65 to 2265 nmol/100 g/body wt, showed a distinct rapid and slow phase in control rats. In GY rats, on the other hand, the rapid phase in copper excretion was absent but the slow phase appeared to be unaffected. Pretreatment of rats with diethylmaleate to deplete hepatic and biliary glutathione abolished the rapid phase of copper excretion in control rats, while the slow phase remained unaffected. No significant effect of diethylmaleate on the hepatic handling of exogenous copper was observed in GY rats. The maximal capacity of the slow copper excretion pathway was 40-45 nmol/hr/100 g body wt, both in control and GY rats; the capacity of rapid excretion pathway depended on the administered copper load. Intravenous injection of copper induced the biliary excretion of a substantial amount of zinc in control rats, but not in GY rats. These results indicate the existence of at least two distinct biliary excretory pathways for copper in the rat, i.e. a slow and a rapid pathway, with a glutathione dependency of the latter only. The basal excretion of (endogenous) copper, in contrast to that of zinc, can proceed independently of glutathione excretion. However, glutathione appears to be involved in the rapid secretion of excess copper. PMID- 2322292 TI - Inhibitory studies of mexiletine and dextromethorphan oxidation in human liver microsomes. AB - The cytochrome P-450dbl isozyme (P-450bdl) is responsible for the genetic sparteine-debrisoquine type polymorphism of drug oxidation in humans. To investigate the relationship between mexiletine oxidation and the activity of this isozyme, cross-inhibition studies were performed in human liver microsomes with mexiletine and dextromethorphan, a prototype substrate for P-450dbl. The formation of hydroxymethylmexiletine and p-hydroxymexiletine, two major mexiletine metabolites, was competitively inhibited by dextromethorphan. Mexiletine competitively inhibited the high affinity component of dextromethorphan O-demethylation. In addition, there was a good agreement between the apparent Km values for the formation of both mexiletine metabolites and the high affinity component of dextromethorphan O-demethylation and their respective apparent Ki values. Several drugs were tested for their ability to inhibit mexiletine oxidation. Quinidine, quinine, propafenone, oxprenolol, propranolol, ajmaline, desipramine, imipramine, chlorpromazine and amitryptiline were competitive inhibitors for the formation of hydroxymethylmexiletine and p hydroxymexiletine as for prototype reactions of the sparteine-debrisoquine type polymorphism. Amobarbital, valproic acid, ethosuximide, caffeine, theophylline, disopyramide and phenytoin, known to be non-inhibitors of P-450dbl activity, were found not to inhibit the formation of these mexiletine metabolites. Moreover, the formation of both metabolites was strongly inhibited by an antiserum containing anti-liver/kidney microsomes antibodies type I (anti-LKMI) directed against P 450dbl. These data suggest that the formation of two major metabolites of mexiletine is predominantly catalysed by the genetically variable human liver P 450dbl. PMID- 2322293 TI - Relationship between reductive drug metabolism in tumour tissue of anthracyclines in microspherical form and anti-tumour activity. AB - Increased activity against a rat solid tumour of doxorubicin incorporated into protein microspheres and administered intratumourally was associated with both increased duration of exposure of tumour tissue to native drug and anaerobic bioreduction of doxorubicin to 7-deoxyaglycones, indicating formation of reactive drug intermediates within tumour tissue. To investigate which of these aspects of drug disposition determined activity we have compared the in vivo fate (clearance from and metabolism by tumour tissue) of doxorubicin in microspherical form with the analogue 4'-deoxydoxorubicin and related this to the tumour growth delay recorded for these drugs. Within the dose range 42 to 55 micrograms, growth delay (14-18 days) of doxorubicin in microspherical form was markedly superior to drug in solution, whereas growth delay of 4'-deoxydoxorubicin in microspherical form (4.3-7.2 days) was not greater than drug in solution. Metabolism to 7 deoxyaglycones by tumour tissue was not a prominent feature of either drug when administered in solution. However, in microspherical form both drugs were extensively metabolized (peak concentrations: 3.6 micrograms/g doxorubicin 7 deoxyaglycone; 2.5 micrograms/g 4'-deoxydoxorubicin 7-deoxyaglycone). Native drug concentrations in tumour tissue were similar after administration in microspherical form at 48 hr (doxorubicin 3.8 micrograms/g; 4'-deoxydoxorubicin 3.7 micrograms/g) and 72 hr (doxorubicin 2.4 micrograms/g; 4'-deoxydoxorubicin 2.7 micrograms/g). At both time points, following administration in microspherical form, tumour tissue concentrations of doxorubicin were significantly greater than when drug was administered in solution, whereas no significant differences were observed for 4'-deoxydoxorubicin. The results are inconsistent with the process of anaerobic bioreduction of doxorubicin to 7 deoxyaglycones being an important component of its anti-tumour activity in microspherical form and point to the importance of increased duration of exposure to native drug. PMID- 2322294 TI - Reactivity of diflunisal acyl glucuronide in human and rat plasma and albumin solutions. AB - Diflunisal acyl glucuronide (DAG) is a major metabolite of diflunisal (DF) in rats and humans. We have investigated the reactivity of DAG, in purified albumin solutions and plasma from both rat and human sources, along three interrelated pathways: rearrangement via acyl migration to yield positional isomers of DAG, hydrolysis of DAG and/or its isomers to liberate DF, and formation of covalent adducts of DF (via DAG and/or its isomers) with plasma protein. Two initial concentrations of DAG (ca. 50 and 10 micrograms DF equivalents/mL) were used throughout. In all incubations, the order of quantitative importance of the reactions was: rearrangement greater than hydrolysis greater than covalent binding. At pH 7.4 and 37 degrees, degradation of DAG in albumin solutions (e.g. half-life ca. 95 min in fatty acid-free human serum albumin) was retarded in comparison to that found in buffer alone (half-life ca. 35 min). Degradation in unbuffered rat and human plasma containing heparin was comparable to that found in buffer. Maximal covalent binding to protein was achieved after 4-8 hr incubation, and was greatest for fatty acid-free human serum albumin (165 ng DF/mg albumin). Thereafter, slow degradation of the adducts was observed. Formation of DF-plasma protein adducts in vivo was also found in rats and humans dosed with DF. PMID- 2322295 TI - Effect of acute ethanol administration on the subcellular distribution of iron in rat liver and cerebellum. AB - An acute ethanol load (50 mmol/kg, i.p.) produced altogether a decrease in the non-heme iron content of the serum and an increase in the iron content in liver and cerebellum. Subcellular fractionation studies indicated that the non-heme iron accumulated by the liver, 4 hr after the ethanol load, was recovered in light mitochondria, microsomes and cytosol, and that iron accumulated by the cerebellum was localized in heavy mitochondria, light mitochondria, microsomes and cytosol. The low molecular weight chelatable (LMWC) iron content as well as the percentage of total non-heme iron represented by LMWC-iron were increased in the cytosol of liver and cerebellum after the ethanol load. These results suggest that an acute ethanol load induces (i) a shift in the distribution between circulating and tissular non-heme iron; (ii) an increase in the cytosolic LMWC iron which, by favouring the biosynthesis of reactive free radicals, may contribute to lipid peroxidation in liver and cerebellum. PMID- 2322296 TI - Hydroxylation of the thiophene ring by hepatic monooxygenases. Evidence for 5 hydroxylation of 2-aroylthiophenes as a general metabolic pathway using a simple UV-visible assay. AB - The 5-hydroxylation of tienilic acid by rat liver microsomes was measured by a new, simple method involving the detection of 5-hydroxytienilic acid by UV visible spectroscopy. This assay allowed continuous detection of this metabolite and could be easily used to determine the kinetic parameters of the reaction (Vmax and Km being respectively 1 +/- 0.2 nmol product formed/mg protein/min and 14 +/- 2 microM for liver microsomes from phenobarbital-treated rats). This activity was found to be dependent on NADPH and to be inhibited by CO, SKF 525A and metyrapone, indicating that it is dependent on cytochromes P-450. This UV visible assay is based on intrinsic properties of 5-hydroxy 2-aroylthiophenes which exist as highly conjugated anions at physiological pH and exhibit large epsilon values around 390 nm. Its application to other 2-aroylthiophenes like suprofen, 2-parachlorobenzoylthiophene and a series of 2-aroylthiophenes with various substituents on the aroyl group showed that, in general, thiophene compounds bearing a 2-arylketo substituent appear to be hydroxylated at position 5 by rat liver microsomes. The kinetic parameters of the 5-hydroxylation of suprofen and 2-parachlorobenzoylthiophene by liver microsomes from phenobarbital treated rats were determined and found to be similar to those for tienilic acid hydroxylation. PMID- 2322297 TI - Investigations on the relationship between DNA ethenobase adduct levels in several organs of vinyl chloride-exposed rats and cancer susceptibility. AB - The levels of 1,N6-ethenodeoxyadenosine (epsilon dAdo) and 3,N4 ethenodeoxycytidine (epsilon dCyd) were measured in DNA of several target organs of vinyl chloride (VC)-exposed rats. Seven-day-old (group I) and 13-week-old (group II) BD VI rats were exposed during 2 weeks to 500 ppm VC in air (7 hr per day and 7 days per week). epsilon dAdo and epsilon dCyd were measured by a combination of prepurification of DNA hydrolysates by HPLC and competitive radioimmunoassay using specific murine monoclonal antibodies. Both ethenodeoxynucleosides were detected in liver, lungs and brain (levels ranging from 0.6 x 10(-7) to 1.3 x 10(-7) for epsilon dAdo/2'-deoxyadenosine and from 1.95 x 10(-7) to 4.92 x 10(-7) for epsilon dCyd/2'-deoxycytidine) but not in kidneys of group I rats. In group II rats, only liver DNA was analysed and the levels of each adduct were six times lower than in young (group II) rats. These findings are in good agreement with the organotropism and the age-related sensitivity of VC-induced carcinogenesis in rodents. PMID- 2322298 TI - The pharmacokinetics of polymer-bound adriamycin. AB - Adriamycin (ADR) covalently bound to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers via biodegradable (Gly-Phe-Leu-Gly) oligopeptide sequences shows antitumour activity against model tumours in vivo. In this study we have examined the distribution of ADR bound to such HPMA copolymers following intravenous administration to mice (ADR concentration 5 mg/kg). An established fluorimetric HPLC method was used to measure levels of free ADR in plasma and tissue samples, and a new technique was developed to quantitate levels of polymer-bound anthracycline. The high initial levels of free ADR in plasma observed following administration of free drug were absent in the case of polymer-bound ADR, and the subsequently high levels of free ADR seen in other tissues were also abolished. In contrast, the circulating half-life of HPMA copolymer-ADR was approximately 15 times longer than that of the free drug. The initial peak level of free ADR in the heart was reduced 100-fold following administration of drug-conjugate. These alterations in pharmacokinetics may account for the decreased toxicity and improved efficacy reported previously. PMID- 2322299 TI - Reaction kinetics of 4-methoxy ortho benzoquinone in relation to its mechanism of cytotoxicity: a pulse radiolysis study. AB - Rate constants quantifying the reactivity of 4-methoxy ortho benzoquinone, formed in the metabolic activation of 4-hydroxyanisole, a possible melanocytotoxic drug under current assessment as a treatment for malignant melanoma, have been determined by pulse radiolysis. The quinone is reactive towards the thiols cysteine (k = 3.5x10(5)M-1sec-1), glutathione (k = 3.1x10(5)M-1sec-1) and dithiothreitol (k = 3.5x10(5)M-1sec-1), but relatively unreactive towards other nucleophiles such as arginine (k less than or equal to 1M-1sec-1) and glutamine (k less than or equal to 1M-1sec-1). Redox exchange with ascorbate also occurs (k = 1.0x10(4)M-1sec-1). In view of the low reactivity of 4-methoxy ortho benzosemiquinone towards oxygen (k less than or equal to 10(5)M-1sec-1) and the model lipid trans-2-butenoic acid (k less than or equal to 2x10(5)M-1sec-1), it is unlikely that initiation of lipid peroxidation by the semiquinone is a major source of cytotoxicity. A more likely toxicity pathway appears to be covalent addition reactions of 4-methoxy ortho benzoquinone with cellular nucleophiles, especially thiols, and/or redox exchange reactions of the quinone leading to antioxidant depletion. PMID- 2322300 TI - Bioactivation of N-arylhydroxamic acids by rat hepatic N-acetyltransferase. Detection of multiple enzyme forms by mechanism-based inactivation. AB - Enzymatic N,O-acyltransfer of carcinogenic N-arylhydroxamic acids such as N hydroxy-2-acetylaminofluorene (N-OH-AAF) results in the production of reactive electrophiles that can bond covalently with nucleophiles and also can cause inactivation of acyltransferase activity in a mechanism-based manner. Incubation of partially purified rat hepatic N-acetyltransferases (NAT) with N-OH-AAF resulted in extensive inactivation of N-OH-AAF/4-aminoazobenzene (AAB) N,N acetyltransferase and acetyl coenzyme A (AcCoA)/procainamide (PA) N acetyltransferase activities, whereas AcCoA/p-aminobenzoic acid (PABA) N acetyltransferase activity was inhibited only slightly. Affinity chromatography with Sepharose 6B 2-aminofluorene (2-AF) resulted in the separation of two NAT activities. NAT I primarily catalyzed the AcCoA-dependent acetylation of PABA; NAT II catalyzed, N,N-acetyltransfer (N-OH-AAF/AAB), AcCoA/PA N-acetyltransfer and N-OH-AAF N,O-acyltransfer (AHAT) activities. Most of the AcCoA/2-AF N acetyltransferase activity eluted in the NAT II fraction. Results of inactivation experiments with N-OH-AAF and the NAT II fractions suggested that one NAT isozyme was responsible for catalyzing the N-OH-AAF/AAB, AcCoA/PA and N,O-acyltransfer reactions and that inactivation of NAT II correlated with the extent of covalent binding to protein. Further purification of the NAT II fractions by chromatofocusing resulted in a 1300-fold purification of the N-OH-AAF/AAB activity and the coelution of N-OH-AAF/AAB, AcCoA/PA and N,O-acyltransferase activities. These studies indicate that N,O-acyltransfer, arylhydroxamic acid dependent N-acetylation of arylamines (N,N-acetyltransfer), and AcCoA-dependent N acetylation of PA may be catalyzed by a common enzyme in rat liver, whereas a second enzyme is responsible for the AcCoA-dependent N-acetylation of PABA. PMID- 2322301 TI - Inhibition of ox brain glutamate dehydrogenase by perphenazine. AB - Factors affecting the inhibition of ox brain glutamate dehydrogenase (GDH) by the antipsychotic drug perphenazine have been studied. Inhibition was found to be of mixed type with respect to 2-oxoglutarate and competitive towards NADH. However, the data indicate that perphenazine binds to a site distinct from the catalytic site to which NADH binds. Perphenazine also enhanced the high-substrate inhibition by these two substrates. Inhibition by perphenazine was not affected by the allosteric effector GTP but it was enhanced by increasing pH, in the range of 6.3 to 7.6, and diminished by increasing ionic strength. Low concentrations of perphenazine relieved the inhibition of GDH by phosphatidylserine and cardiolipin. However, at higher concentrations phosphatidylserine did not interfere with the inhibition by perphenazine whereas cardiolipin relieved it. The possible significance of these interactions in terms of the behaviour of this antipsychotic drug in vivo are discussed. PMID- 2322302 TI - Thermodynamics of the interaction of aristololactam-beta-D-glucoside with DNA. Ionic strength dependence of enthalpy and entropy. AB - The interaction of aristololactam-beta-D-glucoside with calf thymus DNA has been studied by measuring the changes in the absorbance of the alkaloid over a wide range of temperatures and sodium chloride concentrations. The binding parameters obtained are best fit by the neighbour exclusion model. The salt and temperature dependence of the binding constants are used to estimate the thermodynamic parameters involved in the interaction of the alkaloid with DNA. It is observed that aristololactam-beta-D-glucoside binding to DNA is an exothermic process over the entire range of salt and temperature, and the estimated values of enthalpy and entropy change are strongly dependent on the ionic strength of the solution. The enthalpy and entropy changes compensate one another to produce a relatively small Gibbs' free energy change. The possibility that aristololactam-beta-D glucoside exists as a monovalent cation at neutral pH and the possible molecular contribution to the enthalpy and entropy changes of the aristololactam-beta-D glucoside-DNA complex are discussed. PMID- 2322303 TI - Studies on the cellular pharmacology of N-(4-methylphenylsulfonyl)-N'-(4 chlorophenyl)-urea. AB - The cellular pharmacology of N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl)-urea (MPCU) has been examined in a cloned line of GC3 human colon adenocarcinoma cells. There was a rapid concentrative accumulation of drug, which could be separated into energy-independent and -dependent phases. Accumulation over 15 sec was linear and temperature dependent, but not energy dependent (azide insensitive). The rate of uptake was a linear function of concentration over a wide range (0.0026 to 5 mM). No saturation kinetics were demonstrated. Steady state was achieved within 10 min, and drug levels associated with GC3/C1 cells exceeded the extracellular concentration by 4- to 6-fold. This second phase "concentrative accumulation" of drug was azide sensitive. When cells were incubated to steady state in the presence of azide, removal of azide (with addition of glucose) resulted in a further uptake of sulfonylurea to a higher steady state. When [3H]MPCU was removed from the medium after achieving steady state, loss of drug from cells was rapid (T1/2 approximately 130 sec), and no tight-binding component was apparent. After achieving steady state, cell associated drug was lost into drug-containing medium reaching a lower steady state if 10 mM azide (+/- glucose) was added. These data indicate that MPCU may enter cells by a non-saturable energy-independent process (passive diffusion) and bind weakly to some intracellular component or become sequestered to some compartment in an energy-dependent manner. PMID- 2322304 TI - The effect of streptozotocin-induced diabetes on the in vivo acetylation capacity and the in vitro blood N-acetyltransferase activity of the adult male Sprague Dawley rat. AB - Induction of experimental diabetes using streptozotocin significantly reduced the extent of sulphamethazine acetylation by Sprague-Dawley rats. This treatment did not significantly change the total amount of sulphonomide excreted in the urine. The in vitro blood N-acetyltransferase activity of rats treated with streptozotocin was significantly higher than that of untreated animals. Increasing the in vitro glucose concentration of blood samples from both groups significantly increased the amount of acetylsulphamethazine produced. PMID- 2322305 TI - Competition of nucleoside transport inhibitors with binding of 6-[(4-nitrobenzyl) mercapto]purine ribonucleoside to intact erythrocytes and ghost membranes from different species. AB - The potency of nucleoside transport inhibitors, including 6-[(4-nitrobenzyl) mercapto]purine ribonucleoside (NBMPR), dilazep, mioflazine and its derivatives soluflazine and R57974 as inhibitors of the binding of [3H(G)]NBMPR to intact erythrocytes and respective ghost membranes from human, mouse and hamster was determined. There was no close agreement between the IC50 profiles for the different inhibitors when comparing values obtained for intact cells and membranes from each species, and there was no consistent profile of differences when considering individual drugs and comparing their actions in the three species. Present data also were compared with potency values obtained previously with the same drugs directly in nucleoside transport inhibition studies with erythrocytes from the same species as well as with [3H(G)]NBMPR binding studies in isolated liver and lung membranes from hamster. The overall conclusion from this and previous studies is that the evaluation of relative potencies in screening of potential nucleoside transport inhibitors is best carried out at the level actual nucleoside transport studies in intact cells, since [3H(G)]NBMPR binding studies yield discrepant data. PMID- 2322306 TI - 1-substituted phthalazines as probes of the substrate-binding site of mammalian molybdenum hydroxylases. AB - The interaction of a series of 1-substituted phthalazine derivatives with partially purified aldehyde oxidase from rabbit, guinea-pig and baboon liver, and with bovine milk xanthine oxidase, has been investigated. Of the 18 compounds examined, rabbit liver aldehyde oxidase metabolized 10, whereas guinea-pig and baboon liver enzyme oxidized 13 and 14, respectively. Where metabolites were characterized, oxidation was shown to occur at position four of the phthalazine ring. Km values ranged from 0.003 to 1.8 mM. In contrast, most compounds were competitive inhibitors of bovine milk xanthine oxidase with Ki values ranging from 0.015 to 1.3 mM; the cationic derivative 2-methylphthalazinium iodide was oxidized to 2-methyl-1-phthalazinone by both aldehyde oxidase and, with a much reduced affinity, by xanthine oxidase. In terms of structure-metabolism relationships, Vmax values were relatively insensitive to the electronic effects of substituents, but a trend for the more lipophilic derivatives to show increased affinities (Km and Vmax/Km) towards aldehyde oxidase could be seen. However, calculations of molecular size revealed a species-dependent cut-off threshold above which compounds were not metabolized. Results suggest that the relative size of the active site for hepatic aldehyde oxidase is in the order baboon greater than guinea-pig greater than rabbit, and that in spatial terms the active site of bovine milk xanthine oxidase is similar to that of baboon liver aldehyde oxidase. Thus, the binding site of rabbit liver aldehyde oxidase, a widely used source of the oxidase, is apparently more restricted than in some other species. PMID- 2322307 TI - Age-dependent decrease in the hepatic uptake of taurocholic acid resembles that for ouabain. A possible role of surface membrane protein mobility. AB - Isolated hepatocytes were prepared from Wistar-derived male rats of different ages (4, 12 and 27-29 months) by the collagenase perfusion method. The hepatic uptake rate of taurocholate (TC) for the saturable fraction was calculated by subtracting the non-saturable fraction from the total hepatic uptake. The Vmax and the apparent affinity constant Km were computed for the saturable fraction by means of non-linear regression. The Vmax (nmol/mg protein/min, mean +/- SE) for young rats (N = 6) was 2.15 +/- 0.11, whereas in old rats (N = 4) the value was 50% lower (1.16 +/- 0.11, P less than 0.005). In contrast, Km (microM) values were not significantly different between young (25.88 +/- 1.90) and old (30.34 +/ 4.96) rats. There was a significant inverse linear relationship (r = 0.79; P less than 0.01) between the age of rats and the uptake velocity (nmol/mg/mg protein/min) at 1 microM of TC, suggesting a steady and almost linear decrease of TC uptake velocity with age. The rate of decrease per month (2.1%) was quite close to the value for ouabain uptake (2.8%) previously found by the authors. Furthermore, a marked linearity was observed between the average values for TC uptake rates for three age groups and corresponding lateral diffusion constants of hepatocyte plasma membrane proteins previously obtained by the authors using the fluorescence recovery after photobleaching method. The results support our previous proposal that protein mobility within the hepatocyte surface membrane may play at least a partial role in regulation of carrier-mediated hepatocyte uptake functions for various materials. PMID- 2322308 TI - Intracellular iron redistribution. An important determinant of reperfusion damage to rabbit kidneys. AB - These studies were designed to examine the possible role of low molecular weight intracellular iron chelates (desferrioxamine-available (DFX-A) iron) in the damage which occurs during cold storage and subsequent reperfusion of kidneys. The level of DFX-A iron increased significantly (P less than 0.005) in the cortex of rabbit kidneys rendered cold ischaemic (CI) for 24 hr and the amount of iron available for DFX chelation increased significantly (P less than 0.05) in both the cortex and medulla of kidneys stored for 48 or 72 hr compared with fresh non ischaemic controls. During ex vivo reperfusion of the organs with an oxygenated asanguinous perfusate, DFX-A iron returned rapidly to pre-ischaemic levels in 24 hr CI kidneys, but remained elevated following 48 and 72 hr CI (P less than 0.05 compared with 24 hr CI kidneys after 5 min reperfusion), returning to control levels only after 30 min reperfusion. There was no concurrent increase in total iron levels, indicating that a redistribution of iron to more accessible pools had occurred within the tissue. We suggest that decompartmentalization of intracellular iron during ischaemia and raised DFX-A iron levels over an extended period during subsequent reperfusion are responsible for increased catalysis of oxygen-derived free radical-mediated lipid peroxidation, and are an important factor in the deterioration of physiological function observed in rabbit kidneys following extended periods of cold storage. PMID- 2322309 TI - Antiproliferative effects of glutathione S-transferase inhibitors on the K562 cell line. PMID- 2322310 TI - Binding of colchiceine to tubulin. Mechanisms of ligand association with tubulin. AB - Colchiceine, a closely related structural analog of colchicine possessing a C ring tropolone, has been shown to be a potent inhibitor of microtubule assembly in vitro (I50 = 20 microM). The mechanism of inhibition is mediated through binding to tubulin (KA = 1.2 +/- 0.7 x 10(4) M-1), although potentially not through the colchicine receptor site. Supporting the hypothesis of an alternate receptor are the observation of colchiceine binding to the isolated colchicine tubulin complex (KA = 2.2 +/- 1.0 x 10(4) M-1), the poor correlation between the competitive inhibition of colchicine binding (KI = 125 microM) and the inhibition of microtubule assembly, and different structure-activity relationships for colchiceine analogs as compared to the colchicine series. PMID- 2322311 TI - Evidence for a direct role of intracellular calcium in paracetamol toxicity. AB - There is considerable evidence that an increase in cytosolic Ca2+ is involved in the cytotoxicity of a variety of agents. However, the direct demonstration of such involvement has proved difficult. In the present study, loading of freshly isolated hamster hepatocytes with the Ca2+ specific chelator Quin 2 (2-[(2 bis[carboxymethyl]amino-5-methyl-phenoxy)methyl]-6-methoxy-8- bis [carboxymethyl]amino-quinoline) provided significant protection against the loss of viability caused by paracetamol. This was evident both when the cells were co incubated with Quin 2-AM and paracetamol, and when the cells were incubated with Quin 2-AM after prior exposure to paracetamol and its complete removal from the hepatocytes. These observations provide direct evidence that an increase in intracellular Ca2+ is the cause of cell death in hepatocytes exposed to paracetamol. Further, the fact that Quin 2 is protective even after some time suggests that, for alterations of cytosolic Ca2+ to be detrimental, they must be sustained. The effects of Quin 2 on plasma membrane blebbing of paracetamol exposed hepatocytes were less pronounced than on cell viability. This is in contrast to the effects of the direct-acting thiol-reducing reducing agent, dithiothreitol, which was equally effective in preventing blebbing and loss of viability. It is concluded that alterations of cytosolic Ca2+ are less directly linked to plasma membrane blebbing than to loss of cell viability. PMID- 2322312 TI - Ethanol and synaptosomal calcium homeostasis. AB - The effect of ethanol on synaptosomal calcium homeostasis was studied in the rat using the fluorescent dye, fura-2, and 45Ca uptake. The mitochondrial poison, cyanide, caused a substantial rise in intracellular free Ca2+ concentration, [Ca2+]i, over that of control synaptosomes. This rise was enhanced by ethanol. Ethanol also augmented the rise in [Ca2+]i induced by ouabain, indicating that modulation of Na(+)-Ca2+ exchange is probably not the underlying mechanism. The Ca2+ channel blockers, verapamil and La3+, also failed to inhibit the rise in [Ca2+]i caused by ethanol. Preincubation of synaptosomes with caffeine, however, caused a significant decrease in the rise of [Ca2+]i due to ethanol, suggesting that ethanol exerts effects on Ca2+ homeostasis at the level of the endoplasmic reticulum. PMID- 2322313 TI - Effect of xenobiotics on monooxygenase activities in cultured human hepatocytes. AB - The activity of human cytochrome P450 monooxygenases, aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase can be increased by 3 methylcholanthrene, phenobarbital and ethanol in human hepatocytes maintained in primary culture. Total cytochrome P450 content increased two-fold after 48 hr of incubation with methylcholanthrene or phenobarbital and 1.5-fold after incubation with ethanol. The three chemicals elicited different effects on cytochrome P450 dependent activities. Addition of 3-methylcholanthrene caused a time- and concentration-dependent increase in both monooxygenase activities, aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase, while phenobarbital and ethanol increased 7-ethoxycoumarin O-deethylase activity but had no effect on aryl hydrocarbon hydroxylase. Dexamethasone per se had little or no effect on either monooxygenase activities, but potentiated the effect of the three chemicals on 7-ethoxycoumarin O-deethylase. PMID- 2322314 TI - Metabolism of fluperlapine by cytochrome P450-dependent and flavin-dependent monooxygenases in continuous cultures of rat and human cells. AB - The metabolism of fluperlapine, a neuroleptic dibenzazepine derivative with a N methyl-piperazinyl substituent, was investigated in continuous cultures of rat and human cells which express various cytochrome P450-dependent monooxygenase activities. The differentiated rat hepatoma cells H4IIEC3/G- and their variants 2sFou and FGC-5 metabolized fluperlapine predominantly by N-oxygenation and only to a minor degree by N-demethylation or glucuronidation of primary phenolic products. Total fluperlapine metabolism in dedifferentiated rat hepatoma cells H5 and partially differentiated human hepatoma cells HepG2 was much smaller than in the differentiated rat hepatoma lines. This was primarily attributable to their low capacity for N-oxygenation. Human lung adenocarcinoma lines NCI-H322 and NCI H358 formed only trace amounts of fluperlapine N-oxide. Pretreatment of 2sFou cells with benz(a)anthracene, phenobarbital or dexamethasone markedly increased the formation of N-demethylated and glucuronidated products but did not affect the rate of N-oxide formation. Guanethidine and cysteamine, inhibitors of flavin dependent monooxygenase activity, reduced fluperlapine N-oxidation more strongly than aldrin epoxidation, a marker for cytochrome P450 activity. In contrast, n octylamine inhibited aldrin epoxidation but was without effect on fluperlapine N oxygenation. The results suggest that certain cells in continuous culture are capable of expressing flavin-dependent monooxygenase(s) in addition to cytochrome P450-containing monooxygenases. Such cells may offer useful systems for studying the oxidative metabolism of a broad spectrum of xenobiotics and analysing the importance of the two oxygenation reactions for the biological effects of their substrates. PMID- 2322315 TI - Primary culture of proximal tubular cells from normal rat kidney as an in vitro model to study mechanisms of nephrotoxicity. Toxicity of nephrotoxicants at low concentrations during prolonged exposure. AB - The aim of this study was to set up an in vitro system to study nephrotoxicity of xenobiotics which allows exposure at low concentrations for long periods (1-5 days). A very pure preparation of isolated proximal tubular cells (PTC) from rat kidney (Boogaard et al., Toxicol Appl Pharmacol 101: 135-143, 1989) was brought into primary culture. Cells grew to confluence in 3 days and could be maintained up to 8 days in a modification of Dulbecco's modified Eagle's medium Ham F12 nutrient mixture supplemented with fetal calf serum. Fibroblast growth was completely suppressed by replacement of L-valine by D-valine and of L-arginine by L-ornithine. Polarity was retained: in cells grown on filters organic anions were transported at the basolateral membrane while D-glucose transport was located at the apical membrane. Inhibition of the latter was used to assess the functional integrity of the cells after exposure to nephrotoxins. The newly grown cells expressed gamma-glutamyltranspeptidase activity since incubation with the glutathione-conjugate of 1,1-dichloro-2,2-difluoroethylene (DCDFE) induced cytotoxicity. Both beta-lyase and acylase activities were expressed because the cysteine-S-conjugate and the corresponding mercapturate of DCDFE showed cytotoxicity. Cultured cells showed toxicity on prolonged exposure to very low concentrations of gentamicin, cephaloridine, cisplatin and the cysteine-S conjugate of chlorotrifluoroethylene. The lowest concentrations at which toxicity can be observed are 1-3 orders of magnitude lower in primary cultures than in freshly isolated PTC in suspension. This indicates that this cell model is suitable to investigate mechanisms of nephrotoxicity in vitro, at prolonged exposure to the low concentrations that are relevant in vivo levels. PMID- 2322316 TI - Generation of volatile hydrocarbons from amino acids and proteins by an iron/ascorbate/GSH system. AB - Incubation of free, but not of peptide-bound methionine in an iron/ascorbate system resulted in ethylene generation, which was inhibited by glutathione. Leucine and isoleucine, however, when incubated in an iron/ascorbate/GSH system, released small amounts of propane and ethane, respectively. Peptide-bound leucine additionally yielded butane, as did bovine serum albumin or casein. Hydrocarbon generation from amino acids was inhibited by hydroxyl radical scavengers, but catalase and superoxide dismutase were more efficient. Additionally, ethane and propane generation in this system was optimal at pH 6.2 suggesting the involvement of protonated superoxide besides OH-radicals which attack the side chains of Leu and Ile and very probably produce carbon-centered radicals, which should abstract a hydrogen atom from the thiol group of GSH resulting in the formation of saturated hydrocarbons. PMID- 2322317 TI - Characterization of endopeptidase 3.4.24.11 ("enkephalinase") activity in human plasma and cerebrospinal fluid. AB - The presence of the neutral metallo-endopeptidase 3.4.24.11 ("enkephalinase") activity was investigated by fluorimetric assay in human body fluids. Although the enzyme was previously known to occur exclusively in membrane bound form in the human or animal central nervous system, its activity was detected in human cerebrospinal fluid (CSF), plasma and amniotic fluid. Although the endopeptidase 3.4.24.11 activity found in human body fluids has properties closely related to the membrane bound enzyme such as affinity constant for the inhibitors, optimal pH and Km for the substrate, the Vmax values were in CSF, plasma and amniotic fluid, respectively, 2 x 10(3), 10(2), 10 lower than mouse brain homogenate. PMID- 2322318 TI - Determination of soluble cAMP-dependent protein kinase activity in guinea-pig tracheal smooth muscle. Preferential use of kemptide as a phosphorylating substrate. AB - A method is described for the determination of soluble (cytosolic) cyclic AMP (cAMP)-dependent protein kinase (A-kinase) activity in guinea-pig tracheal smooth muscle. The method relies upon the use of either histone or kemptide as a phosphorylating substrate. The relative merits of each of these substances were compared by studying the effects of a protein kinase inhibitor (PKI) and of Na+ on the phosphorylation of each substrate. PKI induced a concentration-dependent inhibition of basal and cAMP-stimulated phosphohistone formation but could not abolish it. Phosphokemptide formation was abolished by equivalent concentrations of PKI. Elevations in Na+ concentration in the reaction buffer inhibited cAMP stimulated phosphohistone formation in a concentration-dependent manner with concomitant elevations in the enzyme activity ratio. Basal or cAMP-stimulated phosphokemptide formation was not inhibited by elevated Na+ concentrations. When tissues were homogenized in high Na+ concentration buffers, an increase in the basal A-kinase activity was observed using kemptide as the substrate. No apparent change in cAMP-stimulated activity was observed. Concomitant with this was an elevation in the enzyme activity ratio. However, a high Na+ concentration in the homogenizing buffer elevated basal phosphokemptide formation and the activity ratio. Separation of the isoenzymes of the enzyme yielded three peaks of activity upon assay of the fractions, which comprised free catalytic subunits (5% total activity), type I holoenzyme (5% total activity), and type II holoenzyme (90% total activity). Enzyme activity was increased upon pretreatment of tissues with isoprenaline and forskolin using both histone IIa and kemptide as phosphorylating substrates. The data support the preferential use of kemptide over histone IIa as a phosphorylating substrate during the determination of A-kinase activity in guinea-pig trachealis. The potential benefits of the use of kemptide are discussed. PMID- 2322319 TI - Stereoselective pharmacokinetics and metabolism of the enantiomers of cyclophosphamide. Preliminary results in humans and rabbits. AB - [R(+),S(-)]-Cyclophosphamide [(R,S)-CP] is an anticancer drug, containing a chiral phosphorous atom, which is prepared and used clinically as the racemic mixture. A new high-performance liquid chromatographic assay suitable for pharmacokinetic studies of CP enantiomers in plasma has been reported recently by this laboratory (Reid et al., Anal Chem 61: 441-446, 1989). Briefly, the assay involves ethyl acetate extraction of CP enantiomers from plasma followed by derivatization to diastereomers in a two-step process utilizing chloral and (+) naproxen acid chloride. Chromatographic analysis was performed on a reversed phase (ODS) column with detection at 232 nm. In the present study, preliminary results on the applicability of this assay to pharmacokinetic studies are presented. Several rabbits were used to compare the influence of i.p., i.v., and oral routes of administration on the stereoselective disposition of (R,S)-CP. Following i.p. administration, S-CP was cleared faster than R-CP. Following oral administration, only R-CP was detectable in plasma, while i.v. administration resulted in minor or no stereoselective disposition. These results indicated that there was a marked stereoselective metabolism of the S-CP enantiomer, with the i.p. and oral routes producing the greatest differences due to first-pass metabolism. Incubation of rabbit-liver microsomes with (R,S)-CP demonstrated that the monooxygenase system can exhibit marked stereoselectivity in its metabolism of CP. The ratio of R-CP to S-CP in the incubation medium increased during the incubation period from 1:1 initially to 4.5:1 after 60 min. The results from the experiments with rabbits indicate that the first-pass metabolism of this drug is highly stereoselective; in contrast, cancer patients who had received (R,S)-CP as an i.v. infusion showed no stereoselectivity in the elimination of the enantiomers. Pharmacokinetic studies with cancer patients, receiving (R,S)-CP as an oral dose, are in progress in order to determine if stereoselective first-pass metabolism of this drug also occurs in humans. PMID- 2322320 TI - Serum lipid abnormalities in heart transplant recipients: predominance of HDL2 like particles in the HDL pattern. AB - Accelerated coronary atherosclerosis is a major risk limiting long-term survival after heart transplantation and is commonly associated with dyslipoproteinemia even in subjects who were not dyslipoproteinemic before intervention. The purpose of this study was to analyse the abnormalities in the lipid profiles of 2 different groups of heart-transplanted males: 18 subjects with underlying ischemic heart disease (IHD) and 19 subjects with non-obstructive cardiomyopathy of unknown aetiology (CM). Both groups were compared to 33 healthy males. All patients were under immunosuppressive therapy including prednisone, cyclosporin A and azathioprine. A moderate hyperlipidemia was found in all transplant recipients, associated with high HDL-cholesterol concentrations in the CM group (1.80 +/- 0.37 vs. 1.29 +/- 0.23 mmol/l) and normal HDL-cholesterol levels in the IHD group (1.40 +/- 0.23 mmol/l). HDL subfractionation showed a marked increase in HDL2-cholesterol (CM: 1.12 +/- 0.32; IHD: 0.69 +/- 0.28; control: 0.40 +/- 0.17 mmol/l) while HDL3-cholesterol was significantly lower than in the control group. Analysis of HDL particle sizes showed in all transplant subjects an increase of an intermediate size particle HDL2a (diameter 9.0 +/- 0.10 nm) which is a minor form in control subjects. In the CM group, both the common HDL2b (10.2 +/- 0.13 nm) and HDL2a were abundant in 13 of 17 patients. The pattern was more heterogeneous in the IHD group but witnessed to a high frequency of HDL2a particles either alone (5/14) or associated with larger HDL2b (4/14) or with small HDL3 (4/14).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322321 TI - Correlations between serum lipids and complement components in adults without demonstrated atherosclerotic disease. AB - The variability due to age and sex and the reciprocal relations of serum IgG, IgA, IgM, C3, C4, total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) were studied in 87 subjects (46 men and 41 women, aged 20-75 years) selected for the absence of significant atherosclerotic lesions. Serum IgA and C3 were higher in men than in women (P less than 0.05) mainly in the age group 41-60, while IgM and HDL-C were higher in women than in men (P less than 0.05 and P less than 0.01, respectively), especially in the age group 20-40. Direct univariate correlations with age were found for serum TC (P less than 0.0001), IgA (P less than 0.001), and C4 (P less than 0.01) but the latter correlations was confirmed only in women by multivariate analysis. These 3 variables had the major increment in the age group 41-60 in men, while in women the increase associated with age was more progressive or late. Univariate analysis showed a 'ring' of highly significant correlations (P less than 0.0001) involving serum lipids and complement components (TC-C4-C3-TG-TC). The correlation between TC and C4 was present only in men in multivariate analysis and improved with increasing age. These findings might represent a clue to explain the previously reported association between serum C4 and atherosclerosis. PMID- 2322322 TI - Lack of association between dietary alcohol and HDL-cholesterol concentrations in obese women. AB - The relationships of alcohol intake and corpulence to HDL-cholesterol were studied in 653 women taking medical advice about body weight. The body mass index (BMI) was positively correlated with triglyceride and negatively with HDL cholesterol. The relation between BMI and HDL-cholesterol was discontinuous. Total cholesterol, triglycerides and diastolic blood pressure were increased for alcohol intakes greater than 10 g/d regardless of body weight. Alcohol intake was associated with higher concentrations of HDL-cholesterol (P = 0.006) in non obese (BMI = 25.2 +/- 1.5 kg/m2) subjects, but not in mildly (27.3 less than or equal to BMI less than 32.3) or massively (BMI greater than or equal to 32.3) obese subjects. The fact that HDL concentrations were not associated with alcohol intake in obese patients suggests that (1) alcohol acts on the HDL pool through one of the pathways which are perturbed in obesity, possibly lipolysis, (2) obesity is one of the reasons for the differences in individual responses of HDL cholesterol to alcohol, (3) myocardial infarction might not be inversely correlated with alcohol intake in the obese as it is in the non-obese population. PMID- 2322323 TI - Aortic antioxidant defence mechanisms: time-related changes in cholesterol-fed rabbits. AB - In 24 rabbits fed a hyperlipidic diet (0.5% cholesterol, 5% lard and 5% peanut oil) for 10 (group A1), 30 group B1) and 60 days, (Group C1), compared to 24 control rabbits fed a standard diet for the same periods, antioxidant defence system (total superoxide dismutase, catalase, total thiol compounds selenium dependent and selenium-independent glutathione peroxidase, glutathione reductase, glutathione transferase) and lipid peroxidation (thiobarbituric acid-reactive substances) in the aortic wall were tested. The percent of intima with grossly apparent atherosclerosis, is assessed by staining with the lipophilic dye Sudan IV, was negligible in group A1, but increased progressively in groups B1 (22.7 6.7%) and C1 (56.8-8.8%). Compared to the controls, a significant rise in superoxide dismutase activity was observed after 30 days of hyperlipidic diet, with a further marked increase at 60 days. Total thiol compounds and selenium dependent glutathione peroxidase activity rose progressively from 10 to 30 and 60 days in cholesterol-fed rabbits. On the contrary, catalase, glutathione reductase and glutathione transferase activities significantly decreased in all experimental groups. Selenium-independent glutathione peroxidase activity was not detectable. Thiobarbituric acid-reactive substances increased about 3 times in hyperlipidemic rabbits. In conclusion, the changes in aortic antioxidant defence mechanisms and lipid peroxidation precede the massive vascular lipid infiltration in cholesterol-fed rabbits; some antioxidant mechanisms are stressed (superoxide, dismutase, glutathione peroxidase, total thiol compounds), whereas others are depressed (catalase, glutathione reductase, and glutathione transferase), thus potentially reducing or increasing vascular susceptibility to oxidative injury. PMID- 2322324 TI - The antihypertensive drug propranolol enhances LDL catabolism and alters cholesterol metabolism in human cultured fibroblasts. AB - The effects of 3 beta-blockers with different pharmacological properties (non selective: propranolol; beta 1-selective: metoprolol; and with intrinsic sympathomimetic activity: pindolol) were comparatively studied on LDL and lipid metabolism in human fibroblasts. At 10(-4) M, propranolol increased low density lipoprotein binding, uptake and degradation by 1.5-, 2.2- and 1.8-fold, respectively, whereas metoprolol and pindolol had no effect. This effect of propranolol is mainly due to an increase in LDL receptor number. Propranolol also enhanced sterol, triacylglycerol, fatty acid and phospholipid synthesis by 2-3 fold from sodium acetate. Cholesterol esterification by oleic acid was significantly and specifically decreased 4-fold by propranolol. Metoprolol and pindolol affect neither sterol synthesis nor cholesterol esterification. Pretreatment of cultured fibroblasts with propranolol induced an increase in hydroxymethyl-glutaryl-coenzyme A reductase activity and a decrease in acyl coenzyme A: cholesterol-O-acyltransferase (ACAT) activity. Propranolol inhibited the induction of ACAT activity by exogenous cholesterol. Preincubation of a cell free extract with propranolol also induced inhibition of ACAT activity. Propranolol decreased the cholesteryl ester content of cultured cells. These effects of propranolol on LDL and cholesterol metabolism might be related to the amphiphilic properties of the drug and suggest an effect on the cholesterol intracellular traffic. The decrease in cholesterol esterification and in the cholesteryl ester cellular level induced by propranolol may be involved in its antagonizing effect on experimental atherogenesis. PMID- 2322325 TI - Lipoprotein abnormalities in patients with extra-coronary arteriosclerosis. AB - Serum levels of lipids, lipoproteins and apolipoproteins A-I and B were evaluated in 102 patients (75 males and 27 females; ages 58 +/- 8 and 61 +/- 7 years (mean +/- SD), respectively) with arteriosclerosis of the lower limbs of supra-aortic trunks. Compared to findings in 64 healthy, age-matched control subjects, male patients in both groups had significantly higher serum triglyceride levels (+42%, P less than 0.05), while female patients with lower limb arteriosclerosis showed significantly increased cholesterol and triglyceride concentrations (+19%, P less than 0.01 and +82%, P less than 0.05, respectively). LDL-triglycerides were also increased in all patients. HDL-cholesterol was significantly decreased in male patients with arteriosclerosis of the lower limbs (-27%, P less than 0.01) and the supra-aortic trunks (-28%, P less than 0.01), and in females of both groups ( 26%, P less than 0.01 and -20%, P less than 0.01, respectively); in terms of percent, HDL2-cholesterol was reduced 2-fold compared to HDL3-cholesterol. Patient apolipoprotein A-I and B levels were unchanged. In male and female patients, correlations between triglycerides and HDL-cholesterol as well as HDL2 cholesterol were negative, but not significant; on the other hand, both correlations were negative and significant in male controls, while only the correlation between triglycerides and HDL2-cholesterol was negative and significant in the female controls. Since HDL-cholesterol, and in particular HDL2 cholesterol, concentrations seem closely related to the intravascular catabolism of triglyceride-rich lipoproteins, the absence of a significant correlation between these parameters in the patients suggests a possible alteration in this metabolic process. PMID- 2322326 TI - Breast carcinoma found in association with reduction mammaplasty. PMID- 2322327 TI - Self-mutilation in combat-related PTSD. PMID- 2322328 TI - Extrapolation of Th metabolism from beagle to humans. PMID- 2322329 TI - Surgical vs. conservative treatment for spontaneous ICH. PMID- 2322330 TI - Psychoactive drug use and AIDS. PMID- 2322331 TI - Cancer and psychosocial traits, continued. PMID- 2322332 TI - Withholding cardiopulmonary resuscitation. PMID- 2322333 TI - Case 28-1989: pulmonary infiltrates and an axillary mass. PMID- 2322334 TI - Clinical and phenotypical characteristics of pre-T-cell leukemia. PMID- 2322335 TI - Physicians who have lost their malpractice insurance. PMID- 2322336 TI - Surveying sexual attitudes. PMID- 2322337 TI - The genome project: pro and con. PMID- 2322338 TI - CF screening. PMID- 2322339 TI - DNA fingerprinting. PMID- 2322340 TI - Re: 'AIDS and traditional health beliefs and practices of black women'. PMID- 2322341 TI - Avian rhinotracheitis diagnostic kit. PMID- 2322342 TI - An organizational study of hazard communication. The health provider perspective. AB - Without question, the more involved nurses were in the elements of hazard identification and MSDS collection and review, the more they knew about the hazardous substances and work processes at the facility. But for the most part, nurses did not participate in Haz Com programs. The process of hazard communication is complicated by the serial transmission of information through a channel of actors, from chemical manufacturers, to managers, to health and safety professionals, and finally, to workers. The larger the number of health and safety professionals in the company, the more health and safety functions were specialized and the less nurses knew about the role of safety and industrial hygiene. The ability of the organization to affect the transfer of hazard information through nurses, by policies or procedures which sharply define the limits of health functions and safety functions, is supported by observations which transcend any individual variances among production sites and nurses. PMID- 2322343 TI - Success and failure attributions in smoking cessation among men and women. AB - 1. Smoking behavior is intermingled with a very complicated array of social and psychological processes which suggests the presence of sociocultural factors that directly influence smoking behavior. 2. Social and cultural factors which distinguish former smokers from smokers indicate that behavioral factors may be related to the ability to successfully stop smoking. 3. Evidence suggests that attributional patterns differ according to gender, with women being more external and employing more luck attributions than men. 4. When attribution and self efficacy expectations were combined with demographic variables, increased understanding of the cessation process increased and predictive power of success in smoking cessation improved. PMID- 2322344 TI - OSHA internship experiences. PMID- 2322345 TI - Neural tube defects: a study in Puerto Rico. AB - Recent literature reports an apparent decline in the incidence of neural tube defects throughout the world. A revision of stillbirth certificates and surgical reports of closure procedures for open neural tube defects was done in order to establish the incidence and its trend during a nine year period in Puerto Rico. The current prevalence of the syndrome was estimated using the death certificates in addition to the fore-mentioned surgical reports. Our results indicate that Puerto Rico carries probably the highest incidence of the US territories and that the trend is not declining one. PMID- 2322346 TI - Pterygium surgery in the office. PMID- 2322347 TI - [Medical tourism in Washington, DC]. PMID- 2322348 TI - Assessment and management of food safety risks. AB - The scientific community believes that the U.S. food supply is as safe as any. Obviously, there are areas in need to improvement and it is clear that the scientific priorities are different from those of the lay public. There is concern that these differences in priorities have been translated into policy that may be misdirected. Such misdirected by policy could result in the less than optimal use of finite resources. One solution proposed to solve this dilemma is to improve risk assessment techniques and to more effectively communicate concepts related to risk. All must share this responsibility. PMID- 2322349 TI - Gastric campylobacter-like organisms and active antral gastritis in Puerto Rico. AB - We attempted to verify if the reported association of gastric campylobacter like organisms (GCLO) with active antral gastritis holds true in our population. All patients undergoing elective upper endoscopy were eligible for the study unless they had a history of gastric cancer or previous antrectomy. Biopsy specimens from 100 consecutive patients were examined blindly for the presence of inflammatory activity and/or intestinal metaplasia. The presence of GCLO was determined by the acridine orange fluorescence technique. A total of 131 antral biopsies examined were classified as either normal, active gastritis, chronic gastritis with activity and chronic gastritis without activity. GCLO were identified in 84% of the biopsies with inflammatory activity (active gastritis and chronic gastritis with activity). However, GCLO were found only in 11% of those biopsies with chronic gastritis without activity. It is therefore our conclusion that the previously reported association of GCLO with active gastritis holds true for our population. PMID- 2322350 TI - Prevalence of intestinal parasites in a rural community in north-central Puerto Rico. AB - A hematology and parasitological survey was conducted in Bayaney, Hatillo, a rural community located in north-central Puerto Rico. A surprising finding was the comparatively high proportion of eosinophilia observed (43 of 83 individuals: 52%). Of these same 83 individuals 16 were found positive for intestinal helminth eggs using the modified Ritchie formol-ether concentration method, which uses 1 gram of feces. When eosinophilia was in the 5 to 10% range, 35% were also found to be infected with one helminth parasite. When eosinophilia was in the 10 + % range, 75% of the individuals were also found to be infected with one helminth parasite. The helminth eggs or larvae found were: hookworm (n = 8), Strongyloides stercoralis (2), Trichuris trichiura (5), and one individual with a combined infection of hookworm and Trichuris. Fifteen of the 16 (94%) individuals with intestinal helminth infections had eosinophilia ranging from 5 to 40%. Of a subgroup of 5th grade school children, 11 of 35 (31%) had eosinophilia ranging from 5 to 17%, but only two of these also had helminth eggs (Trichuris). No intestinal protozoan parasites were found. Although all infected individuals were apparently asymptomatic, they were informed of the results of the survey and contacted for additional medical examination and treatment, where applicable. An ELISA for anti-S. mansoni egg antibodies using a cationic antigen fraction denoted CEF-6 was done with the serum of 44 individuals of which 20 were a high risk group because of frequent water contact. Only one (2%) was found positive by serology and this one was negative for S. mansoni eggs by coprology. Additional studies are warranted to elucidate the etiology of eosinophilia in the absence of helminth infection. PMID- 2322351 TI - Cardiopulmonary resuscitation: what patients say. PMID- 2322352 TI - Percutaneous nephrostolithotomy: alternative for patients in renal failure secondary to bilateral staghorn calculi. AB - Percutaneous nephrostolithotomy is a well known and accepted procedure for the management of renal stones and particularly for debulking of staghorn calculi. Herein we present the case of a patient in renal failure due to bilateral staghorn calculi who was rescued from dialysis after bilateral percutaneous nephrostolithotomies. PMID- 2322353 TI - A study on diet, nutrition and disease in the People's Republic of China. Part I. PMID- 2322354 TI - [Tissue reactions with administration of piezoelectric shock waves in lithotripsy of salivary calculi]. AB - Before clinical application of an extracorporeal piezoelectric lithotripter to treat sialolithiasis, tissue reaction during shockwave application was examined in vitro and in experiments with animals. Application of shockwaves to human tissue in vitro showed neither macroscopic nor microscopic effects. In animal experiments, the acute experiment (16 rabbits, Chinchilla-Bastard) revealed minor bleeding in the parenchyma of the parotid gland, while the chronic experiment (14 rabbits, Chinichilla-Bastard) revealed no morphologic tissue damage to the parotid region of the rabbit, as a result of piezoelectric shockwaves. However, when the eye was placed in the shockwave focal area and the shockwaves were transmitted via the fissura orbitalis to the endocranium, brain damage could be detected morphologically. In conclusion, the authors feel that the clinical application of extracorporeal piezoelectric fragmentation of salivary stones is justified, provided that a reliable positioning of the patient and exact sonographic location of the concrement are possible. PMID- 2322355 TI - [Evoked otoacoustic emissions for hearing screening in infants]. AB - The early detection of auditory dysfunction in neonates and infants is important for the development of language and other cognitive abilities. The registration of evoked otoacoustic emissions is a new way of detecting cochlear hearing disorders. Results in high-risk infants are reported. Evoked otoacoustic emissions promise to be a fast and noninvasive technique to screen auditory dysfunctions in newborns and high-risk infants. PMID- 2322356 TI - [Value assessment of the MIRA (multichannel infant reflex audiometry) hearing evaluation with and without biofeedback. 3. Diagnosis from curves or behavioral observation?]. AB - Basing on the results of behavioural audiometry, MIRA (Multichannel Infant Reflex Audiometry) with and without biofeedback as well as in several cases also from the ABR, the authors demonstrate the advantages of the combination of curve analysis with behavioural observation compared with isolated looking at physiological curves or at the behaviour. The results were obtained from 100 babies in their first year of life accepted in sequence for testing their hearing; nearly one half of them had considerable hearing risks, most of them having been subjected to several different hearing tests. PMID- 2322357 TI - [Adjuvant alternative therapy procedures in idiopathic tinnitus aurium (and in sudden deafness)]. PMID- 2322358 TI - [The Borrelia titer in ENT diseases]. AB - In 139 patients with facial paralysis, sudden hearing loss, vertigo, and lymphadenitis of the head and neck, the prevalence of borrelia burgdorferi serum antibodies was examined with the help of immunofluorescence assays for IgG- and IgM-antibodies, immunofluorescence assays after absorption of cross-reacting antibodies with treponema phagedenis, ELISA, and Western Blot. Six out of 22 patients with facial paralysis, 11 out of 72 with hearing loss, eight out of 45 with vertigo, and five out of 25 with lymphadenitis of the head and neck were seropositive. These patients were compared with a control group of 52 patients without any clinical signs of Lyme disease. The control group consisted of patients admitted for surgery of septal deformities (n = 19), squamous cell carcinomas (n = 27), and pleomorphic adenomas of the salivary glands (n = 6). In nine out of 52 patients in the control group, antibodies against Borrelia burgdorferi were detectable. According to Fisher's exact test, there was no statistical difference between the two groups as regards the prevalence of seropositive patients. Lyme disease is a doubtful major etiologic factor in facial paralysis, sudden hearing loss, or vertigo. PMID- 2322359 TI - [Carcinoid tumor of the middle ear. Morphology, immunohistochemistry, clinical aspects and differential diagnosis]. AB - We describe the unusual case of a carcinoid tumour of the middle ear occurring in a woman of 50 years of age. The tumour exhibited both glandular and neuroendocrine differentiation. Immunohistochemical demonstration of chromogranin A is of particular diagnostic importance as evidence of neuroendocrine differentiation. The morphological spectrum of the middle ear tumours with neuroendocrine and/or glandular differentiation reported in the literature is discussed in detail. These tumours are arranged schematically according to the degree of glandular and of neuroendocrine differentiation, and are compared with the tumours of other regions. The data in the literature do not allow unequivocal assertions concerning the prognosis of carcinoid tumours of the middle ear to be made, and very diverse therapeutic measures have been employed in the reported cases. In our case there is no evidence of recurrence six months after local tumour excision. PMID- 2322360 TI - [Primary adenocarcinoma of the middle ear]. AB - One case of primary adenocarcinoma of the middle ear is reported, which developed from a chronic otitis media. Histological examination established the diagnosis of adenocarcinoma. Its clinical appearance was benign, being restricted to the middle ear and tympanic membrane and with no bone destruction or metastases. Two years after local surgery there was no evidence of recurrence. PMID- 2322361 TI - [Differential diagnosis of ulcerative mucous membrane diseases of the mouth cavity and pharynx]. AB - Nonmalignant ulcerous diseases of the mouth often require repeated histological and clinical observations for several weeks to establish a diagnosis. One patient with Wegener's disease, one with a necrotizing sialometaplasia, and a case of Sutton-type aphthosis outline these difficulties. In all three cases, only a synopsis of histology, laboratory findings, and clinical appearance led to the respective diagnosis. PMID- 2322362 TI - [Differential diagnosis of malignant ulcer of the mouth mucosa--the Sutton aphthae (periadenitis mucosa necrotica recurrens)]. AB - Sutton's ulcer is one of the recurrent oral ulcers. It normally occurs on the nonkeratinized oral mucosa and heals by scar formation. The cause is assumed to be an immunologic response to oral epithelium or the antigen of a microorganism. Therapy is unspecific or topical use of antibiotics and cortisone is recommended. The exclusion of a local or systemic malignant disease seems to be the most important feature of a differential diagnosis. PMID- 2322363 TI - [An unusual differential diagnosis of cancer of the base of the tongue: malacoplakia]. AB - A rare case is presented of a 68-year-old patient, suffering from malacoplakia of the base of the tongue. Up to now, only seven patients with manifestations of this chronic inflammatory disease in head and neck have been reported. Histologic features and therapeutic approaches are discussed, followed by a short review of the literature. PMID- 2322364 TI - [Occurrence of non-metaplastic squamous epithelium within the larynx and its relation to the development of cancer]. AB - The study is concerned with the occurrence and distribution of squamous epithelial areas in the human larynx as well as with the question as to whether inferences with regard to the development of inner laryngeal carcinomas can be made from their location. For this purpose, macroscopic epithelial staining was carried out on 104 cadaver larynxes and the results compared with the tumor location established in macroscopic serial sections of approximately 100 surgical preparations of extirpated larynxes. Special interest was devoted above all to the occurrence of squamous epithelium outside the vocal cord level. The authors found special sites of predilection for carcinogenesis which showed an astonishingly striking correlation with the distribution of the squamous epithelium found in the interior of the larynx in all age groups. Direct carcinogenesis from healthy squamous epithelium is discussed as well as the development of cancer from a metaplastic transformation of ciliated epithelium into squamous epithelium. The results constitute a contribution to early diagnosis of inner tumors of the larynx, since on the basis of the results it appears to be indicated that increased specific attention needs to be paid to the parts of the mucosa which display areas of squamous epithelium with a certain regularity in microlaryngoscopy. PMID- 2322365 TI - [A pathophysiologic thesis of the development of laryngeal cancer]. AB - Mucociliary transport in the subglottic region was assessed in 45 of 75 human larynges that had been removed for carcinoma. These were marked with India ink and observed through an operating microscope. Normal mucociliary pathways in this region are known to be symmetric, conducting all of the mucus of the bronchial tree effectively to the posterior commissure for passage into the hypopharynx. None of the examined larynges showed normal transport patterns. The alteration of mucociliary flow as an early effect of tumor development is not likely. It is therefore concluded that these abnormal mucociliary transport patterns existed before tumor development and wee probably genetically coded. Such an ineffective clearance of airborne pollutants from the subglottic space with prolonged contact times may promote carcinogenesis. This might explain the known variable risk for carcinogenic susceptibility. PMID- 2322366 TI - An analysis of fatal bicycle accidents in Victoria (Australia) with a special reference to nighttime accidents. AB - This paper examines the fatal bicycle accidents which occurred in the period 1981 1984 in Victoria with particular emphasis on nighttime fatalities. The examination provides information on aspects of accident location, environment, problem type, time, and cyclist characteristics. The relationship between actual accidents and cyclists perceived collision danger is also investigated. The characteristics of fatal bicycle accidents are different to those of overall "casualty" accidents. A difference also exists between day and night, and between metropolitan and nonmetropolitan fatal accidents. In the metropolitan area, adult cyclists over 17 years were over-involved in fatal accidents. The proportion of cyclists involved in fatalities at night increases with increase in age. Almost 80% of nighttime accidents occurred on links on arterial roads, and the majority in the high speed limit zones (75 kph and over). A greater proportion of accidents was initiated by cyclists. In 90% of nighttime cyclist fatalities the cyclist was hit from the rear, compared with 40% in daytime. Inadequacy of bicycle and street lighting was found to be an important factor in nighttime fatalities. PMID- 2322367 TI - A comparison of AIS-85 with AIS-80 for injury scaling in blunt trauma. AB - As the effects on injury scaling of the differences between the 1980 and 1985 revisions of the AIS are unknown in blunt trauma, we compared them in all 1270 critically injured (median ISS, 26) blunt trauma patients (75% male, 74% road crash, overall mortality 17%) admitted to the Department of Critical Care Medicine at Auckland Hospital from 1983 through 1987. In 911 patients (72%) there were no differences between AIS-80 and AIS-85 in any body region or in derived ISS. Changes in AIS grades were most common in the abdomen (205 patients), thorax (100 patients), and head (61 patients) regions. Median ISS overall for the 1270 patients was unchanged at 26. One percent of patients had changes in ISS of 16-24 points. Direct comparison of groups of patients scored with these two revisions of the AIS is inappropriate, particularly in those with abdomen region injury. PMID- 2322368 TI - Safety of freeway median high occupancy vehicle lanes: a comparison of aggregate and disaggregate analyses. AB - This paper addresses safety issues associated with High Occupancy Vehicle (HOV) lanes constructed along freeway medians, without physical separation from adjacent traffic. Data associated with operation of such an HOV facility in Southern California are analyzed relative to the pattern of accidents on the facility and the potential role of congestion. Detailed analyses of accident characteristics point out that potentially false conclusions regarding the safety of HOV lanes can be drawn from simple analyses that are based on aggregate measures of accident frequencies and assumed traffic volumes. PMID- 2322369 TI - Comparisons of the thoracic trauma index with other models. AB - The thoracic trauma index (TTI) provides an indication of the severity of injuries received by motor vehicle occupants in side-impact collision environments. The index was derived from results on two sets of cadaver tests. Using a variety of statistical and numerical methods, the authors reanalyzed the data from these 80+ cadaver tests to construct a better measure of injury than TTI. Indices generated by these analyses were compared with TTI using the following quantitative measures: monotonicity, overlap, percentage correct, and sensitivity. The values of these measures are broadly similar for all indices and none of the new indices consistently performs better than TTI. This suggests that TTI is as good a predictor of injury as any of the several alternative models created. PMID- 2322370 TI - The effect of climate on fractures and deaths due to falls among white women. AB - Climatic conditions may affect the incidence of fractures and fall deaths. Analysis of national fatality data shows that among white women, those living in colder climates have higher rates of fall deaths. Fall deaths increase in winter in all regions, but especially so in colder states. In a prospective cohort study of 96,506 predominantly white female nurses 35-59 years of age, we found that, after controlling for personal and lifestyle characteristics, those women residing in colder climate also had a higher incidence of hip and forearm fracture. In colder states, fracture rates were substantially higher in winter than in summer. A cold climate appears to be a significant risk factor for both fractures and fall deaths among white women, particularly as they age. PMID- 2322372 TI - When did a reduced speed limit show an effect? Exploratory identification of an intervention time. AB - In a statistical analysis of accident data before and after a speed limit reduction, the time of the countermeasure is, of course, well known. Our understanding of the accident process may, however, be increased if we assume in a thought experiment that this time is unknown. We ask if the data themselves can tell us something about such a possible time. By means of time series of traffic accidents in Zurich before and after a speed limit reduction, different exploratory methods are presented to identify the "unknown" time of this measure. For most of the investigated series, the most likely time was found to lie in the three months before the true introduction. A possible explanation of this result may be that the media already informed the public before the countermeasure was actually introduced. This finding leads to an improved parsimonious intervention model which distinguishes between a possible "preintervention effect" and the usual "intervention effect." PMID- 2322373 TI - The role of alcohol in nonfatal bicycle injuries. AB - To assess the risk of nonfatal bicycle injury related to blood alcohol concentration (BAC) an unmatched case-control study was conducted in Helsinki in 1986. Eligible cases were the 140 adults injured either in motor vehicle or other bicycle accidents occurring between 3 P.M. and 10 P.M., who arrived at hospital within six hours of injury. Seven hundred bicyclists from the street were randomly selected as controls. BAC was measured with a breathalyzer. A major difference in alcohol involvement was found between cases (24.1%) and controls (4.0%). The injury risk estimate (odds ratio) of an inebriated bicyclist was at least ten-fold at BACs above 100 mg/dl compared to a sober bicyclist. Alcohol increased the bicyclist's risk of injury from falling more than from collision. As an unprotected road user, an inebriated bicyclist greatly increases his own risk of injury but seldom causes danger to other road users. PMID- 2322374 TI - [The use of computers in the Urgent Medical Aid Unit--preparation and planning]. AB - The use of computers in prehospital emergency medicine gives rise to great prospects of achieving high efficacy of the urgent medical aid unit and of directing the group of doctors effectively. Extensive programmes for aiding decisions which are immediately available and can be used in daily practice enable an increase in the quality of emergency treatment. All measures which are necessary for the service in the urgent medical aid unit and the Red Cross of the GDR can be quickly monitored by computers. An easy-to-use programme was worked out. PMID- 2322371 TI - Bicycle accidents and injuries: a pilot study comparing hospital- and police reported data. AB - Bicycle accident and injury data collected by two different samples of North Carolina hospital emergency rooms during the summers of 1985 and 1986 are examined and compared with state police-reported bicycle accident data for the same time periods. Of the 649 emergency room treated bicyclists, 62% were children aged 5-14 and 70% were male. Nineteen percent of the riders suffered moderate or worse injuries (AIS greater than or equal to 2), and 6% were hospitalized. In contrast, less than half of the police-reported accidents involved riders under 15 years of age, 85% of the riders were male, and two thirds suffered moderate or worse injury. Whereas virtually all of the police reported accidents involved a motor vehicle, less than a fifth of the emergency room cases did. Only 10% of the emergency room cases were duplicated on the state accident files. It is estimated that 800 children ages 0-19 are hospitalized annually in North Carolina for bicycle-related injuries, and an additional 13,300 children receive emergency room treatment. PMID- 2322375 TI - [The rescue station--a multidisciplinary treatment unit in the hospital]. AB - The creation of integrative organizational structures are seen as an objective requirement of medicine characterized by progress of knowledge and specialisation. For emergency cases the rescue station has stood the test as a multidisciplinary unit of the hospital. This thesis is confirmed by experiences obtained from practical work in the Frankfurt/Oder District Hospital and by discussions in the "Working Group Rescue Station" of the "Society of Emergency Medicine of the GDR." In order to realize the function of the rescue chain as well as the multidisciplinary motivation, intensive quantitative and qualitative promotion of rescue stations is required. PMID- 2322376 TI - [Rectal premedication using ketamine, diazepam and atropine in childhood]. AB - In 70 children aged between 2 and 14 years the effect of rectal application of ketamine, diazepam and atropine was investigated. Administration was effected by suppositories in 38 children (group A) in four weight classes. Thirty-two children (group B) were premedicated by clysters depending on body weight. We found that the combination of drugs applied in group B showed significantly more effective premedication and enabled smooth induction of anaesthesia. Latency between application and induction was 20 minutes. Since a state of deep sleep can occur rapidly, a preoperative monitoring of the children is necessary. In contrast to group A, we found a smaller increase in heart rate in group B. But there were no differences in behaviour during and after operation between the groups. Despite the relatively small doses of ketamine, 12.8% of all children showed increased salivation. Therefore, this method of premedication should not be used without atropine. Since 11% of the patients vomited postoperatively, the use of dehydrobenzperidol instead of diazepam is discussed. PMID- 2322377 TI - [Hemodynamic changes during the induction phase of halothane-nitrous oxide anesthesia in childhood]. AB - The haemodynamic effects of halothane nitrous oxide anaesthesia were studied in 15 children aged 4-13 using measurements of heart rate, blood pressure and impedance cardiography. The preinduction (control) measurements were compared with measurements obtained one minute after inhalation of nitrous oxide and oxygen, at the beginning of the stage of excitation, at the beginning of the stage of tolerance and after the injection of 0.02 mg/kg atropine. During the induction period blood pressure decreased significantly, while heart rate remained unchanged. Cardiac output was significantly decreased at the stages of excitation and tolerance. Virtually no change in total peripheral resistance occurred. After atropine significant increases in heart rate, mean arterial blood pressure and total peripheral resistance were measured. Cardiac output was increased compared with the pre-atropine values, but not with the control value. Impedance cardiography is a useful non-invasive method of measuring changes of stroke volume during paediatric anaesthesia. PMID- 2322378 TI - [Operability in cardiopulmonary insufficiency]. AB - Based on 48 patients suffering from larger bullous pulmonary emphysema, the problem of operability was investigated. In spite of a considerable preoperative cardiopulmonary insufficiency in several cases the patients were treated surgically. The good postoperative results show that the border lines recognized up to now can be partially ignored without endangering the success of the operation. In patients who have been well adapted to chronic pulmonary insufficiency for years, postoperative respirator treatment should be used sparingly. The decision in favour of an operation must be made individually. PMID- 2322379 TI - [Immediate reaction of the Urgent Medical Aid Unit--current aspects of organization and management]. AB - The dispatcher centres of the Urgent Medical Aid Unit (UMAU) have to guarantee an instant reaction for medical assistance in catastrophes and other serious occurences within the scope of their appointed medical areas. Whereas aid for a group of damaged persons largely takes place according to the principles of individual treatment, in catastrophes medical care must be given according the criteria of disaster medicine until a balance in the initial disproportion between aid requirements and possibilities is reached. The necessary qualification for this is obtained by members of the UMAU through regular postgraduate training. The qualifications of the head of the unit and the senior doctor on the spot are of particular importance. The most important instrument for preparing and implementing immediate reaction is a list of comprehensive and clearly arranged instructions regarding tasks and functions to be carried out. The success of immediate reaction depends in no small way on the availability of facilities, the standard of which has to be critically evaluated. PMID- 2322380 TI - Perianal skin care for persons with an ileoanal reservoir. AB - The perianal skin care and management of skin irritation I have described has been effective in 98% of my patient population. These patients exhibited mild to moderate perianal skin irritation, which was resolved within 24-48 hours. In 2% of the patients, we used stronger antifungal preparations (e.g. Mycostatin Power, Mycolog Cream) or steroid products. These products are expensive and require a prescription. Moreover, the steroid products can only be used for a short period of time, as prolonged use can cause damage to the skin. The ileoanal reservoir is an excellent choice for patients wishing to avoid a permanent ileostomy. Patients selected for this procedure should be under the age of 40 (with a few exceptions) and mentally competent. They must have good anal sphincter control and be highly motivated to follow instructions to obtain the highest satisfaction and the best results from this surgery. The procedure has proven effective when performed by a surgeon who is successful in this field on a patient who is well-educated regarding the surgical procedure, post-operative care, and most importantly, the perianal skin care. This exemplifies a successful candidate for the ileoanal reservoir. PMID- 2322382 TI - Alternative procedures after coloproctectomy. PMID- 2322381 TI - Development and implementation of a skin care program. AB - The incidence of nosocomial pressure ulcers for the identified high-risk patient care areas totaled 21% of the 152 patients in the first skin audit. The incidence of nosocomial pressure ulcers for the second audit of 156 patients was 12%. The second skin audit was accomplished six months after the implementation of a skin care program that included assessment forms, general and unit based education of nursing staff, development and implementation of Standards of Care for Skin Care, and provision of skin care products on the nursing unit. The population characteristics of the total sample indicated a fairly even male-to-female ratio and the average age was 60 to 69 years for both audit populations. The mode for the first audit was age 70 to 79 and for the second was 60 to 69. Most of the sample experienced neurological and musculoskeletal problems that adversely affected the patients mobility. One-fourth of the first sample and 1/2 of the second audit sample were bedridden. One-fifth of both samples experienced incontinence and almost 1/3 of both samples used incontinence devices (Foleys and collectors). PMID- 2322383 TI - Growth hormone-binding sites in chicken hypothalamus. AB - Specific binding of 125I-labelled recombinant DNA-derived chicken GH (rcGH; 2.1 +/- 0.41 (S.E.M.) % of total counts) and of 125I-labelled bovine GH (1.80 +/- 0.27% of total counts) to crude plasma membranes of the chicken hypothalamus was demonstrated. Binding of 125I-labelled rcGH was related to the amount of tissue incubated and was significant over the range 250-950 micrograms membrane protein per tube. Binding of 125I-labelled rcGH was saturable over the range 0.14-0.40 pmol and was to a single class of high-affinity (33.5 pM) low-capacity (2.14 fmol/mg protein) binding site. Binding of 125I-labelled rcGH was displaced by ovine GH and by ovine prolactin. These results demonstrate, for the first time, central GH-binding sites in a vertebrate species. PMID- 2322384 TI - Expression of the epidermal growth factor gene in mouse lachrymal gland: comparison with that in the submandibular gland and kidney. AB - Expression of the epidermal growth factor (EGF) gene in mouse lachrymal gland was studied. The lachrymal gland of adult male and female mice contained immunoreactive EGF at a concentration of 0.013 +/- 0.002 (S.E.M.) and 0.014 +/- 0.003 ng/mg wet tissue respectively. Northern blot analysis of RNA from the lachrymal gland revealed the presence of 4.1-4.3 kb preproEGF mRNA, which was smaller in size than the 4.7-4.8 kb preproEGF mRNA in the submandibular gland and kidney. There was no sex difference in the mRNA level in the lachrymal gland, whereas the mRNA levels in the submandibular gland and kidney of adult male mice were 42-fold higher and twofold lower respectively than those of female animals. Administration of testosterone propionate or L-thyroxine to female mice increased submandibular gland levels of preproEGF mRNA by 35-fold or 12-fold respectively, but caused no change in lachrymal gland levels of preproEGF mRNA. The level of mRNA in the kidney was decreased by administration of androgen to one-third of that in control animals. The mRNA in the lachrymal gland was detected as early as 2 weeks of age and thereafter it remained at a constant level throughout adulthood, while that in the submandibular gland increased greatly during the pubertal stage. These results indicate differential hormonal and developmental regulation of EGF gene expression in the lachrymal gland, submandibular gland and kidney. PMID- 2322385 TI - Molecular cloning of a cDNA for androgen-regulated proteins secreted by the mouse epididymis. AB - A cDNA clone encoding androgen-dependent proteins secreted by the mouse epididymis was isolated by screening a cDNA library using differential hybridization, according to the selective expression of the mRNA in the normal but not in the castrated mouse. Translation of mRNA hybrid-selected by this 1.4 kb clone (M53) yielded proteins of Mr 26,000 which were processed in vitro in the presence of microsomal membranes into proteins of Mr 24,000. Northern blot analysis of epididymal total RNA revealed at least two populations of mRNA (1.4 and 1.8 kb) homologous to the M53 clone, which were restricted to the caput epididymidis. Studies in vivo demonstrated that testosterone regulates the concentration of these mRNA populations. Analysis of epididymal total RNA from ten individual animals provided no evidence that the M53 mRNA populations are the products of allelic variants of a gene. Southern analysis of mouse genomic DNA revealed single bands with most of the tested restriction enzymes. Furthermore, cross-hybridization to the M53 cDNA revealed homologous mRNA species in rat, human, rabbit, ram and boar epididymal RNA. PMID- 2322386 TI - Development of an in vitro model of tumor progression using v-raf and v-raf/v-myc transformed rat liver epithelial cells: correlation of tumorigenicity with the downregulation of specific proteins. AB - A series of clonal cell lines were derived from rat liver epithelial cells after being infected with a defective retrovirus containing either v-raf (3611-MSV) or v-raf/v-myc(J2) together with a helper virus. These clones exhibited a different morphology from the regular cuboid shape of the control cells, infected only with the helper virus. All of the infected cell lines contained at least one full length copy of appropriate proviral DNA and expressed comparable levels of v-raf mRNA, although only the cells transformed with the v-raf/v-myc combination were capable of anchorage-independent growth in soft agar. All of the clones except the controls formed tumors in nude mice but with markedly different latency periods and growth rates. Thus, these cell lines represent an in vitro model for tumor progression. Two-dimensional polyacrylamide electrophoresis was used to investigate changes in cellular protein expression related to malignant conversion. The expression of three proteins of pI/Mr x 10(-3) 5.9-7.2/205 (RP1), 6.5-7.5/160 (RP2) and 4.0/85 (RP3) consistently matched the transformed phenotype. In particular the expression of RP1 and RP2 correlated with the relative tumorigenicity of the cell lines. Rat liver epithelial cell lines transformed by other protocols that did not involve v-raf also showed downregulation of these three polypeptides. Crude fractionation studies determined RP1 to be soluble and RP2 and RP3 to be membrane associated. RP2 was shown to be a glycoprotein containing mannose and galactose residues. These three proteins are consistent markers for the tumorigenic potential of rat liver epithelial cells. PMID- 2322387 TI - Negative growth controls and carcinogenesis. PMID- 2322388 TI - Chromosome site-specific immunohistochemical detection of DNA adducts in N acetoxy-2-acetylaminofluorene--exposed Chinese hamster ovary cells. AB - In these studies a polyclonal antiserum elicited against a carcinogen-DNA adduct was used to explore the localization of DNA adducts in metaphase chromosomes of cultured cells. Morphological visualization of the adduct N-(deoxyguanosin-8-yl) 2-aminofluorene (dG-C8-AF) in Chinese hamster ovary (CHO) cells exposed to the direct-acting carcinogen N-acetoxy-2-acetylaminofluorene (N-Ac-AAF) was accomplished by indirect immunofluorescence with an anti-G-C8-AF antiserum. At the same time the pattern of chromosomal DNA replication was determined by replicative incorporation of bromodeoxyuridine (BrdUrd) and chromosomal staining with anti-BrdUrd. Visualization of DNA in chromosomes was accomplished with Hoechst 33258 dye. When synchronized CHO cells were exposed to N-Ac-AAF for 0.5 h during early S phase, the chromosomal pattern of dG-C8-AF adduct formation was not random. Metaphase chromosome spreads from cells exposed to N-Ac-AAF in different experiments contained certain chromosome regions that had a consistently high adduct concentration. The regions of high DNA damage corresponded to the regions active in DNA synthesis when BrdUrd and the carcinogen were given simultaneously in early S phase. In addition, the patterns of high adduct concentration and replicative synthesis shifted when the carcinogen and BrdUrd were given simultaneously during late S phase. Thus, the stage of cell cycle in which adducts are induced is an important factor in the specific location of the highest concentrations of this type of DNA lesion. PMID- 2322389 TI - Deep partial skin thickness burns: a reproducible animal model to study burn wound healing. AB - A reproducible deep partial skin thickness burn model using guinea-pigs to study the healing process of this injury is described. Round aluminium templates heated to 75 degrees C and applied for 5 s to the moistened, clipped and depilated dorsal skin produced the desired depth of injury. This model is applicable for the study of the three main components of the burn wound healing process: epithelialization, contraction and scar formation. It is recommended that the India ink injection technique be used to confirm the depth of the burn wound. PMID- 2322390 TI - An investigation of the anabolic activity of somatropin in normal and burned rats. AB - A 'blind', cross-over study was performed in 10 control and 12 burned rats which were assigned to receive either biosynthetic human growth hormone (somatropin) or placebo for 5 days each in random order. There was a significant rise in urinary nitrogen excretion and rapid weight loss in the burned rats, which also had significantly lower plasma somatomedin levels than control rats. Somatropin administration resulted in a significant increase in somatomedin levels in control rats only. There was no significant difference in weight or nitrogen balance between somatropin or placebo-treated rats. It is concluded that rats with normal pituitary function are insensitive to the anabolic effects of somatropin and that burn injury abolishes the normal somatomedin response to somatropin. PMID- 2322391 TI - Pulmonary capillary dynamics and fluid distribution after burn and inhalation injury. AB - A non-linear macroscopic mathematical model is described for the simulation of the different mechanisms that regulate the pulmonary capillary dynamics in patients with thermal injury. The techniques used in the construction of the model are those of 'system's dynamics'. This model has been incorporated into a patient simulator, which makes it possible to analyse the fluid and protein exchanges in a burn patient. The regulating mechanisms involved are: the pulmonary circulation, the fluid and protein transfer between the plasma and the interstitial space at the pulmonary capillary level, and the pulmonary lymphatic system. As a result of the sensitivity analyses of the model we propose that, for the simulation of the effects of an inhalation injury at the pulmonary capillary level, the parameters to be altered will be the pulmonary capillary permeability coefficient for proteins and the pulmonary capillary surface damaged by the injury. To verify the validity and utility of the model, the clinical progress of a series of burn patients with lung injuries has been compared with the results obtained using simulation. PMID- 2322392 TI - Use of cultured human epidermal keratinocytes for allografting burns and conditions for temporary banking of the cultured allografts. AB - Five children who suffered burns clinically regarded as full skin thickness loss were grafted with cultured allogeneic skin from newborn prepuce. The wounds had remained open and infected without healing for about 20 days before the patients were received in the burn unit. To avoid losing surviving deep epidermal cells the wounds were debrided but not deeply excised and, a few days before allografting, they were washed with isodine solution and sterile water, and treated with silvadene cream application. All children received 76 cultured allografts of about 60 cm2 each. After allografting, the wounds were epithelized in 7-10 days and the allogeneic grafted skin began desquamation suggesting that the allograft did not 'take' permanently but was replaced by the newly formed skin. On the other hand, since allografting is an adequate therapy to provide early temporary coverage in extensively burned patients, we developed conditions for banking cultured skin to make it available for immediate use. The conditions described allow banking of the cultured grafts for 15-20 days with retention of clonal growth ability similar to that of unstored epithelia. The results show that cultured epidermal cells obtained from human newborn foreskin, when used as allografts for coverage of full skin or deep partial skin thickness burns, allow rapid epithelization of the burn wounds. PMID- 2322393 TI - Paediatric burn injuries in the Jeddah area of Saudi Arabia: a study of 197 patients. AB - A prospective study was conducted on paediatric thermal injury patients admitted to the Burns Unit at King Fahd Hospital, Jeddah, Saudi Arabia over a 2-year period (December 1985 to December 1987). A total of 197 patients (out of 319) were paediatric, aged up to 18 years. Infants and toddlers accounted for 59.4 per cent and adolescents for 14.2 per cent. Scalding and flame injuries accounted for 98 per cent with most injuries occurring at home (97.5 per cent) and the overall paediatric mortality rate was 4.4 per cent. PMID- 2322394 TI - Paediatric burn injuries in New England, USA. AB - The authors analysed a subset of data from the New England Regional Burn Program (NERBP) to describe the epidemiology of burn injuries for children aged from birth to 19 years in the six-state New England area of the USA. The subset of the NERBP data analysed pertained to residents of the six New England states who were admitted to hospital for the treatment of a burn injury sustained between 1 July 1978 and 30 June 1979. Analysis of the data revealed that 1128 (41 per cent) of the 2742 hospitalized burns identified occurred to persons between the ages of birth and 19 years, yielding an overall burn incidence rate of 30.7 burns per 100,000 person-years. Children aged from birth to 2 years sustained a higher burn rate, 96.7 burns per 100,000 child-years, than did children in any other age category. The burn rate for males was higher than the rate for females in each age category, as were the rates for black children compared to white children. Children in Massachusetts experienced the highest overall burn rate among the six New England states; the lowest rate occurred in New Hampshire. Overall, 63 per cent of the burns occurred in a residential setting. The most common activities related to burn injury were food preparation and food consumption, which accounted for 471 (42 per cent) of the burn injuries. PMID- 2322395 TI - Fatal tapwater scald burns in the USA, 1979-86. AB - Four hundred and fifty-nine fatal tapwater scald burn injuries reported to the Injury Information Clearinghouse of the Consumer Product Safety Commission from 1979 to 1986 were studied. Data concerning the 459 deaths were abstracted from the death certificate file maintained by the Clearing house. Risk estimates were derived, using the resident population of the USA as of 1 July 1982 as the midpoint population estimate. Over half the deaths occurred in those over 75 years of age, while about one-fifth of the deaths occurred in children younger than 5 years of age. The crude mortality rate was approximately two deaths per million population over the 8-year period studied. In all age groups, black skinned people experienced an approximate three-fold increase in risk (RR = 3.23, 95% CI: 2.87, 3.63). Among the elderly, males experienced an approximately 50 per cent increase in risk (RR = 1.47, 95% CI: 1.26, 1.72). One of every eight fatal injuries was sustained in a public building or residential institution. Implications of the current findings in terms of targetted prevention efforts are discussed. PMID- 2322396 TI - Role of skin in the burn-induced reduction of reticuloendothelial phagocytic activity in rats. AB - Acute burn trauma has been demonstrated to depress reticuloendothelial system (RES) phagocytic activity, which could partially explain the development of septicaemia in burn patients. In the present study we have attempted to determine the role that skin plays in the depression of the RES. One group of Lewis rats was subjected to a 100 degrees C scald burn for 10 s. Eschar was then removed and implanted onto the backs of a second group of normal controls. A third group of Lewis rats were subjected to sham treatment; the eschar of these animals was removed and implanted onto the back of a fourth group of normal rats. The excision sites of the donor animals were immediately covered with Biobrane. Twenty-four hours later the technetium-99m sulphur colloid [( 99mTS]SC) method described earlier (Trop et al., 1989) was used to determine phagocytosis in these four groups of animals. Acute burn trauma produced a marked reduction in colloid uptake by the spleen and a marked increase in the uptake of colloid material by the lung, although no effect was observed on liver or kidney uptake. Implantation of the burn eschar into normal control rats had no statistically significant effect upon colloid uptake. These data suggest that alterations in phagocytic activity of the spleen and lung occur within minutes after burn injury and may be unrelated to the presence of the burn eschar itself. PMID- 2322397 TI - Thermographic assessment of hand burns. AB - Twenty-three patients with 32 burned hands were studied thermographically within 48 h of injury to investigate the potential value of thermography in the assessment of the depth of hand burns. Superficial and deep partial thickness burns were treated conservatively, with excision and grafting of those which had not healed by 2-3 weeks after injury. This delayed surgery group and the healed group were retrospectively analysed to determine the predictive value of the initial clinical and thermographic assessments of the depth of the burns. Full skin thickness burns were excised and grafted within 5 days and were not included in the study. Initial thermographic assessment correctly predicted the outcome (whether healed or excised and grafted) in 33 of 36 burns. This relationship was highly significant. Initial clinical assessment of depth had no significant relationship with the time taken to heal. Thermography may help in the selection of patients who might benefit from early surgery. PMID- 2322398 TI - Protecting the exposed skin graft--the Norwich cage. AB - A simple method of protecting an exposed skin graft is presented. It is cheap, easy to use, and applicable to most sites of the body, even in areas with contours that might otherwise be thought difficult to protect. PMID- 2322399 TI - A ring burn--electric or contact? AB - A circumferential band of deep burn affecting the ring finger sustained by a car electrician is presented. Although it was caused by short circuiting the car battery by a metal spanner and the ring he was wearing, the injury was purely a contact burn. PMID- 2322400 TI - Novel method of skin substitution in plastic surgery. PMID- 2322401 TI - Demystifying research--what is research and can I do it? AB - The different stages of research can be considered to be the following: hypothesis; proposal; data collection; data analysis; and report writing. PMID- 2322402 TI - Demystifying research--literature searching. PMID- 2322403 TI - Provision of counselling for radiotherapy patients. PMID- 2322404 TI - The value of Korner statistics. PMID- 2322405 TI - CT of epidural lipomatosis: a case report. PMID- 2322406 TI - In the outback. PMID- 2322407 TI - The problems in making a recruitment video. PMID- 2322408 TI - The healing wound: a comparison of three clinically useful methods of measurement. AB - A variety of different methods can be used to measure healing wounds. Among these are: 1) photographs, with subsequent area quantification using a digitizing pad with computer interface; 2) wound tracings; and 3) a Kundin measuring device. The purpose of this study was to compare three different clinically useful methods of measuring the area of healing wounds. Observations of venous stasis ulcers (n = 36) and decubitus ulcers (n = 37) were made on patients recruited from both inpatient and outpatient populations of a large metropolitan hospital. Analysis of the data using Pearson correlation revealed that all three methods were highly correlated, r = 0.93 or above (p less than or equal to 0.001). However, repeated measures analysis of variance among the three methods revealed that they were all significantly different (p less than or equal to 0.001) from each other. It was concluded that: 1) either of the three methods can be used as a valid index of wound area, but 2) acetate tracing should be used to obtain the most accurate measure of actual wound area. PMID- 2322409 TI - Operating room acquired pressure ulcers. AB - Six patients developing sacral pressure ulcers during vascular, cardiovascular and orthopedic surgical procedures are presented. Neither risk rating score nor time spent on the operating table identified these patients at unusual risk. The ulcers were usually not evident until the second postoperative day. The ulcers all had an initial bruise-like appearance or ecchymotic perimeter. They became larger and necrotic despite treatment. Healing did not begin until 12-14 days post-operatively or even longer if additional surgeries were required. A discussion of pressure ulcer development during surgery and recommendations for further study are included. PMID- 2322410 TI - Nurses' documentation about pressure ulcers. AB - Documentation in a patient's medical record is a nurse's legal and professional responsibility. Descriptive charting about pressure ulcers is critical since it may affect treatment modalities. The purpose of this research was to examine what nurses chart about pressure ulcers. The IAET Standards of Care Dermal Wounds: Pressure Ulcers (1987) was used as a guide. Nursing notes from 167 medical records were examined. None of the nurses' notations contained 100 percent of the items examined in this study. The most frequently occurring descriptor was location (74.2%). This research documents deficiencies in nurses' charting about pressure ulcers. PMID- 2322411 TI - Nutritional care plan for pressure ulcers. PMID- 2322412 TI - A magnetic measurement device for the kinematic analysis of unrestrained human hand movements. AB - A magnetic measurement device is described which was constructed to study human hand- and finger-movements. The system overcomes some problems frequently arising in the study of finger grip movements. It allows the simultaneous recording of several positions which cannot be observed with optical devices because they are hidden by other parts of the limb. Trajectories are recorded using small receiver coils moving in an alternating magnetic field of 3 transmitter coils. The performance of subject's movements is not significantly disturbed. A high sampling rate and a lack of mechanical damping permit a high temporal resolution which can analyze rapid movements. Subjects are not exposed to any biological risk or discomfort. Thus, a recording session can be repeated numerous times. The results obtained from this type of apparatus may allow quantification of the course of progressing diseases and to study the effects of remediation. PMID- 2322413 TI - Sleep and EEG slow-wave activity in the domestic cat: effect of sleep deprivation. AB - The 24-h sleep-wake distribution, the vigilance states and the time course of EEG slow-wave activity was investigated in 8 adult domestic cats individually maintained in isolation under 14-h light (06.00-20.00 h)/10-h dim conditions. The frontal EEG and motor activity were continuously recorded for 22 h (during the daily cleaning and food-replenishing period between 07.00 and 09.00 h the cats were only observed). Sleep was prevented for 14 h (07.00-21.00 h) by playing with the animals. Recovery from sleep deprivation was recorded for the remaining 10 h of the dim period. Non-rapid eye movement (non-REM) sleep, REM sleep and waking were uniformly distributed over the light and dim period, with the exception of the 2-h feeding period where the cats were always awake. EEG power density in the delta band (0.75-4.5 Hz; slow-wave activity) was computed in non-REM sleep. The values in the light period were higher than in the dim period. In neither of the lighting periods was a trend observed. After sleep deprivation a small increase of non-REM sleep and REM sleep was present. EEG slow-wave activity was initially enhanced and then declined progressively. We conclude that despite the small circadian difference in the sleep-wake pattern observed in our cats, sleep homeostasis is similar to that observed in other mammalian species. PMID- 2322414 TI - Neglect following unilateral ablation of the caudal but not the rostral portion of medial agranular cortex of the rat and the therapeutic effect of apomorphine. AB - The medial agranular cortex (AGm) of the rat is often considered analogous to the frontal eye field (FEF) of the monkey. However, recent anatomical, physiological, and behavioral evidence indicates that, while the caudal portion of AGm may indeed be an analog of the primate FEF, the rostral portion of AGm may be more similar to the primate supplementary motor area. The current study examined the effects of unilateral ablation of both the rostral and caudal components of AGm on the ability to orient to unilaterally presented stimuli. As expected, lesions of caudal but not rostral AGm resulted in a severe unilateral neglect of stimuli characteristic of rats with lesions of the entire rostral-caudal extent of AGm and of monkeys with FEF lesions. Caudal AGm operates also had more severe neglect than a group of rats from a previous study with larger AGm lesions which damaged the caudal portion of AGm to varying degrees. In addition, a second study showed the dopamine agonist apomorphine to have an acute dose-dependent therapeutic effect on the neglect resulting from caudal AGm ablation similar to that seen in animals with ablation of the entire rostral-caudal extent of AGm. PMID- 2322415 TI - Strain-dependent differences in hippocampal glucocorticoid binding capacity and active avoidance in the mouse. AB - Maximal individual [3H]corticosterone binding capacity in the hippocampus was lower in C57BL/6 mice than in BALB/c mice, and positively correlated with active avoidance learning in the two strains. Moreover, a parallel difference in the activity of hypothalamo-pituitary adrenocortical axis (HPAA) was found, consisting in a level of plasma corticosterone in C57BL/6 higher than in BALB/c mice. These results confirm the genetically determined differences in behavior of C57BL/6 and BALB/c mice, and demonstrate their association with differences in hippocampal corticosterone binding capacity, pointing to a functional relationship between the behavioral and neuroendocrine parameters. PMID- 2322416 TI - Corpus callosum section disrupts motor behaviour strategies during visual discrimination learning in rat. AB - Monocularly patched rats were trained on a series of visual tilt discriminations ordered from simple to difficult to measure the angular difference threshold of each eye. The stereotyped running pattern which the animal made was also recorded. Callosal section disrupted a preoperatively established running pattern and produced an ocular neglect; the animal's performance dropped to chance when it used the eye ipsilateral to the preferred side of approach. PMID- 2322417 TI - Evidence in bimanual finger-tapping of an attentional component to stuttering. AB - The performance of right- and left-handed male and female stutters was compared with that of non-stutters on a bimanual coordination task that involved tapping a key twice with one hand for each single tap of a key by the other hand. Right handed non-stutters performed this 2:1 tapping better when it was the right hand that tapped twice (R2/L1 condition) rather than the left hand (L2/R1 condition), but among left-handers performance was similar under the two conditions. This replicated previous findings of Peters10 that were interpreted as indicating the role of attentional mechanisms in the expression of handedness. The performance of the stutters differed in two major respects. First, overall bimanual tapping rates were significantly slower than those of the non-stutters. Second, right handed stutters did not show the asymmetry in performance between the R2/L1 and L2/R1 conditions. The results are interpreted within the framework of current neuropsychological research that relates stuttering to anomalous mechanisms of interhemispheric communication. PMID- 2322418 TI - Production and characterization of monoclonal antibodies to nivalenol tetraacetate and their application to enzyme-linked immunoassay of nivalenol. AB - Three monoclonal antibodies were obtained by the fusion of mouse myeloma cells with splenocytes isolated from BALB/c mice that had been immunized with 8-hydroxy 3,4,7,15-tetraacetyl-nivalenol hemiglutarate covalently bound to bovine serum albumin. These anti-nivalenol tetraacetate monoclonal antibodies were of the IgG type and highly specific to nivalenol tetraacetate, with an apparent association constant of about 10(8)M-1. The relative cross-reactivities of one monoclonal antibody with nivalenol tetraacetate, acetyl T-2 toxin, and scirpenol triacetate were found to be 1.0, 0.02 and 0.03, respectively. Other derivatives showed no cross-reactivity at all. An indirect enzyme-linked immunosorbent assay (ELISA) based on the competitive binding principle was developed using the antibody from clone D18.102.59. The sensitivity of the system was about 0.1 ng of nivalenol tetraacetate per assay. Comparison of nivalenol levels detected in naturally contaminated barley samples by competitive indirect ELISA and gas chromatography (GC) showed good agreement, indicating that the antibody is useful for the measurement of nivalenol in naturally contaminated cereals and grains. PMID- 2322419 TI - Effects of different heparins on the enhancement of the thrombin-antithrombin reaction. AB - Kinetic analyses were made of the thrombin/antithrombin III (ATIII) reaction in the presence of catalytic amounts of three kinds of mammalian HA-heparin (bovine, pig and whale), which have the same affinities for ATIII. In the absence of NaCl, the first-order rate constant was higher with whale HA-heparin than with the other two HA-heparins. However, the strength of the interactions of thrombin with the HA-heparins was in the order, bovine greater than pig greater than whale. Thus, the slow reactions in the case of bovine and pig HA-heparins were probably due to preferential binding of the two HA-heparins to thrombin rather than to ATIII, thus causing the HA-heparins to be inhibitory for the reaction by reducing the turnover rates of the polysaccharides as catalysts. In the presence of 0.15M NaCl, the first-order rate constants were slightly higher in the case of pig HA heparin than of the other two HA-heparins. Since the strength of the interactions of these HA-heparins with thrombin was in the order, pig greater than or equal to bovine greater than whale, the faster reactions were probably due to higher associations of the enzyme with the essential HA-heparin-ATIII complex. PMID- 2322420 TI - Activation of bovine prothrombin as monitored by the clotting assay. AB - The activation of bovine prothrombin was studied with highly purified clotting factors and using a coagulation assay developed to look at the initial rate of prothrombin conversion as well as the conversion rate over a time course of 75 min. Activation of prothrombin by factor Xa alone was slow. The rate of prothrombin conversion increased markedly with the addition of each of the accessory components Ca2+, phospholipid and bovine factor V, respectively. With the complete prothrombinase complex comprising factor Xa, Ca2+, phospholipid and factor V, the rate increase was about 22,000-fold higher compared to the action of factor Xa and Ca2+ on prothrombin alone. The rates of thrombin formation obtained with activated factor X1 were only about 70% the values obtained with factor X2. The rate of prothrombin activation and the difference between the activities of the activated factors X1 and X2 are discussed. PMID- 2322421 TI - Cellular signals and plasticity in nervous systems. 79. Konferenz der Gesellschaft fur Biologische Chemie. Freiburg i.Br., September 24th-27th, 1989. Abstracts. PMID- 2322422 TI - Effects of human and ovine pancreatic secretory trypsin inhibitors on the proliferation of normal human fibroblasts. AB - Human pancreatic secretory trypsin inhibitor inhibited cell-surface proteolytic activity in human fibroblasts. In the range of concentrations which caused proteinase inhibition, fibroblast proliferation was also inhibited by this reagent and by the ovine equivalent. At lower concentrations, there was some evidence for a mitogenic effect, and this was confirmed by obvious stimulation of DNA synthesis at these concentrations. Human alpha 1-proteinase inhibitor, previously demonstrated to be an inhibitor of fibroblast proliferation, was also mitogenic at concentrations lower than those which inhibited proteolytic activity and cell proliferation. Human pancreatic secretory trypsin inhibitor and epidermal growth factor apparently work through independent mechanisms, since their mitogenic effects are additive. PMID- 2322423 TI - Transition form of microbodies. Overlapping of two sets of marker proteins during the rearrangement of glyoxysomes into leaf peroxisomes. AB - Several forms of microbodies have been characterized on the basis of their biochemical functions. We have investigated cucumber cotyledons which house two different microbody forms during their development. In these cells, a shift from organelles with the enzymes of beta-oxidation and glyoxylate cycle to peroxisomes with the enzymes of the photosynthetic C2-cycle can be induced by light. The transition state and the time course of changes was studied at different levels of gene expression during the first 2 days of illumination, by quantifying the rate of de novo protein synthesis in cotyledons and by measuring the mRNA activities in vitro. Synthesis and turnover of particular proteins were determined during the transition stage by immunoprecipitation of malate synthase, isocitrate lyase, catalase, multifunctional protein, and thiolase, and quantified by fluorography. From the mRNA activities and the rate of protein synthesis, gene expression for enzymes of the glyoxylate cycle and beta-oxidation started to decrease 24-36 h after onset of continuous light. At that time the rate of synthesis of glycolate oxidase, a leaf peroxisomal marker, is already maximal. By pulse-chase experiments 0-48 h after the onset of light the speed and intensity of protein turnover were measured. Rates of proteolytic degradation of individual enzymes indicated that the different enzymes were not lost simultaneously or all at once. This excludes a destruction of the whole organelle by the lytic compartment. PMID- 2322424 TI - Initial characterization of aldehyde dehydrogenase from rat testis cytosol. AB - Aldehyde dehydrogenase was purified 187-fold from cytosol of rat testis by chromatographic methods and gel filtration with a yield of about 50%. The enzyme exhibits absolute requirement for exogenous sulfhydryl compounds and strong dependence on temperature. Addition of 0.4mM Ca2 or Mg2 ions results in 50% inhibition. Optimally active at pH 8.5 and 50 degrees C, aldehyde dehydrogenase displays broad substrate specificity; saturation curves with acetaldehyde and propionaldehyde are non-hyperbolic, with Hill coefficients comprised between 0.8 and 0.7. Strong substrate inhibition can be observed with both aromatic and long chain alyphatic aldehydes. According to mathematical models, Km decreases from 246 microM for acetaldehyde to 4 microM for capronaldehyde and Ki decreases from about 4mM for butyraldehyde to 0.2 mM for capronaldehyde. PMID- 2322425 TI - Acute bone marrow aplasia associated with intravenous administration of deferoxamine (desferrioxamine). AB - The authors report the clinical course and fatal outcome of a case of acute bone marrow aplasia, after intravenous administration of deferoxamine (desferrioxamine) to a 16-year-old girl with homozygous beta-thalassaemia. The type of aplasia was mainly that of a megakaryocytic thrombocytopenia, but the 2 other haemopoetic series were also involved. The absence of any other toxic factors and the quite rapid onset of the bone marrow failure after this type of treatment strongly suggest that intravenous administration of high doses of deferoxamine was the potential toxic factor. PMID- 2322427 TI - International Symposium on Drug Safety. Ottawa, 28-29 September, 1989. Proceedings. PMID- 2322426 TI - Clinical presentation and management of acute 2,4-D oral ingestion. AB - 2,4-D, an extensively used herbicide, was intentionally ingested by a 61-year-old woman. An initial serum 2,4-D concentration of 392 mg/L was measured. The prominent clinical feature was marked central nervous system depression; primary laboratory abnormalities were extreme elevation of creatine kinase activity, and transitory elevation of AST and lactate dehydrogenase enzyme activities. Alkaline diuresis was initiated early and decreased the half-life of the drug from an initial 39.5 to 2.7h. It is concluded that alkaline diuresis to produce urine pH in the range of 7.5 to 8.5 should be considered in the management of an overdose patient with central nervous system depression and a history of 2,4-D ingestion. PMID- 2322428 TI - Pharmacovigilance. The French system. AB - The French system of drug surveillance (pharmacovigilance) is a combination of mandatory reporting and intensive hospital surveillance. The Regional Centres are decentralised but coordinated through a national network. An algorithm index is used to assess the relationship between drugs and adverse effects. The adverse reactions alert system is produced by the compilation and analysis of the cases entered in a data bank (8062 in 1988) and by the analysis of queries from general practitioners (20,000 in 1988). The duties of the centres are also to provide information, analyse data and to improve the safe use of drugs. PMID- 2322429 TI - Safety considerations in product development. AB - In drug development, about 1 in 1000 interesting compounds reaches the market. Drug safety is only relative and needs to be considered in the context of efficacy. Ultimately, the standards of safety and efficacy are determined by society. Drug safety can be enhanced by adequate patient education, i.e. patients should understand their disease as well as the risks and benefits of their medication. There is often considerable public pressure on the Government and regulatory authorities to alter some aspects of the drug development process. While we should not engage in poor science or alter regulations unthinkingly, the process should be re-examined and re-evaluated as the usual methods of evaluating risk/benefit may not be suitable for a particular disease or patient population. Public pressure has influenced changes in the USA, such as the parallel track testing, early release of drugs etc. It is important to realise that absolute toxicity is rare. Relative toxicity is more usual but may be influenced by many factors such as disease processes, drug dose, duration of administration, kinetic parameters or immunological factors. Clinical considerations in the drug development process include the predictability of adverse reactions in some patient populations, problems of over-dosage, unexpected drug-drug interactions and availability of patient monitoring. Economic factors such as total cost of the drug regimen, availability of alternative therapies, expense of sponsor initiated special studies and surveillance, liability risk and the potential cost of altered labelling, warning notices and even market withdrawal are also considered. Thus, there are general guidelines, but the clinical, safety and toxicity considerations involved in the development of each drug may be special or unique. PMID- 2322430 TI - Exact random-walk models in crystallographic statistics. V. Non-symmetrically bounded distributions of structure-factor magnitudes. AB - Derivations of exactly formulated Fourier-series representations of probability density functions (p.d.f.'s) of the magnitude of the structure factor are based on the fact that the structure factor and its real and imaginary parts are bounded. In some situations the bounds of the real and imaginary parts of the structure factor are different, and this gives rise to modified forms of the p.d.f.'s. Three physical examples that call for such modifications are investigated: (i) effect of dispersive scatterers on the p.d.f. of a centrosymmetric structure factor, (ii) effect of the presence of a centrosymmetric fragment in the asymmetric unit of a non-centrosymmetric space group, and (iii) effect of heavy scatterers in special positions of a non centrosymmetric space group, where the imaginary part of the trigonometric structure factor for these special positions vanishes by symmetry. The general form of an exact Fourier p.d.f., taking account of such modifications, is derived, and expressions for Fourier coefficients are obtained for selected examples of the above three situations. It is seen that the effects of pseudocentrosymmetry may be most pronounced and those of dispersion are significant mainly in the range of small values of the structure factor. PMID- 2322431 TI - About the Coulomb potential in crystals. AB - The Coulomb potential in a crystal is discussed. It is shown that its Fourier series expansion has a singularity for the V(0, 0, 0) component, which is important when comparing different compounds, or when using the Coulomb potential as a probe for reactivity. Methods to calculate this term are discussed. Sum rules for multipolar moments of crystals in terms of structure factors are derived, which are of interest for the comparison of microscopic and macroscopic dielectric properties. PMID- 2322432 TI - Sodium content and sodium efflux of mononuclear leucocytes from young subjects at increased risk of developing essential hypertension. AB - Mononuclear leucocytes were used as a cellular model for the in vitro measurements of volume, sodium and potassium content, sodium efflux rate constants and absolute sodium efflux in order to assess any cellular changes in young men at increased risk of developing essential hypertension, and to analyze whether any such changes were associated with borderline hypertension and/or heredity. Four groups of subjects were evaluated: 28 normotensive (NTO) and 20 borderline hypertensive (BHO) offspring of hypertensives, 12 borderline hypertensives with normotensive parents (BH) and 28 normotensive subjects with normotensive parents (NT). The cellular sodium/potassium contents of the four groups were not discernibly different. Ouabain insensitive sodium efflux rate constant and corresponding absolute efflux were significantly increased in offspring of hypertensives. Ouabain sensitive absolute sodium efflux was significantly increased in borderline hypertensives (BHO + BH) compared to normotensives (NT + NTO). These results indicate that leucocytes from subjects predisposed to hypertension possess an increased ouabain insensitive sodium transport mechanism and in subjects with borderline hypertension the sodium potassium pump seems activated. PMID- 2322433 TI - Comparison of clinic and home blood pressure levels and the role of the sympathetic nervous system in clinic-home differences. AB - Plasma and urine norepinephrine, epinephrine and home blood pressure were measured in 48 young hypertensive men (mean age, 21 years) and 25 matched normotensive controls. Plasma samples were drawn following 30 min rest in the clinic and 24 h urine samples were collected at home. Twenty-one hypertensive patients were given a single dose of clonidine (150 micrograms orally). Changes in blood pressure, heart rate and plasma norepinephrine were assessed. Twenty five of the hypertensive patients were found to have a normal home blood pressure (defined from records of the normotensive subjects). The other group of patients maintained a high home blood pressure. In comparison to normal subjects, patients with a high home blood pressure were characterized by higher urinary norepinephrine and epinephrine excretion and higher plasma epinephrine. Patients with a normal home blood pressure had normal heart rate at home, normal plasma and urinary catecholamines. However, the two groups of hypertensives could not be distinguished on the basis of clinic blood pressure, plasma or urinary catecholamines due to considerable overlap. At 90 min after oral clonidine administration, the plasma norepinephrine and blood pressure levels were decreased in both groups of hypertensives to a similar extent. The changes in heart rate were significantly smaller in patients with a high home blood pressure than in those with a normal home blood pressure. These results suggest that the patients with a high home blood pressure tended to have a high sympathetic nerve activity. However, the two groups of hypertensives could not be separated on the basis of plasma or urinary catecholamine measurements. PMID- 2322434 TI - Absence of behavioral differences in young normotensive adults as a function of parental history of hypertension. AB - It has been previously demonstrated that mildly hypertensive subjects show deficits in their performance on various sensory-perceptual, cognitive, and psychomotor tests relative to matched normotensive control subjects, and that these behavioral deficits are reversible following treatment with antihypertensive medication. To examine whether these deficits are an outcome of elevated blood pressure, rather than preceding the hypertensive state, normotensive offspring of hypertensives and normotensives were administered a test battery. Results showed that with minor exceptions, offspring of hypertensives and offspring of normotensives performed similarly on the tests. These results suggest that the behavioral deficits seen in hypertensives arise subsequent to the onset of elevated blood pressure. PMID- 2322435 TI - DOCA-salt treatment decreases serum total calcium but not ionized calcium concentrations in rats. AB - We examined whether or not DOCA-salt treatment to rats would decrease serum ionized calcium concentrations in relation to the enhanced hypotensive response to the calcium antagonist nifedipine. DOCA-salt treatment increased blood pressure and enhanced the hypotensive effects of nifedipine. Serum total calcium and albumin levels were clearly reduced, but the ionized fraction of calcium was not altered by treatment with DOCA-salt for 4 weeks. The total serum calcium concentration, but not the ionized calcium, significantly correlated with serum albumin in DOCA-salt rats. A reduction in serum ionized calcium may therefore not be induced by DOCA-salt treatment and may not be related to the enhanced depressor response to nifedipine. PMID- 2322436 TI - Effect of back support and stethoscope head on seated blood pressure determinations. AB - Seated BP measurements were taken in 48 men with a history of essential hypertension: in a chair with back support v on an examining table with no back support, and with bell v diaphragm stethoscope head in each condition. There were no significant differences between bell and diaphragm in SBP or DBP determinations. SBP was not significantly different between table and chair, but table DBP was 6.5 mm Hg higher (P less than .0001) than chair DBP. We conclude that back support, but not bell v diaphragm stethoscope head, affects seated BP determinations. PMID- 2322437 TI - Thromboxane mediation of the pressor response to infused angiotensin II. AB - The role of thromboxane A2(Tx) in mediating the pressor response to angiotensin II (AII) was studied in anesthetized rats. Intravenous AII (500 ng/kg/min) increased mean arterial pressure (MAP) by 35 +/- 3 mm Hg and increased the excretion of prostaglandin PGE2, the metabolites of prostacyclin (6kPGF1 alpha) and Tx (TxB2) (P less than .05). A similar pressor infusion of the alpha 1 adrenoreceptor agonist phenylephrine (PE) increased the excretion of PGE2 and 6kPGF1 alpha but not TxB2. The increases in MAP and prostaglandin excretion produced by AII were reversed by the AII-receptor antagonist saralasin (10 micrograms/kg/min) while those produced by PE were reversed by the alpha adrenoreceptor antagonist phenoxybenzamine (250 micrograms/kg). The Tx receptor antagonist, SQ-29,548 (8 mg/kg) attenuated (P less than .0001) the AII-induced rise in MAP (13 +/- 1 mm Hg) but did not modify the pressor response to PE. The Tx synthetase inhibitor, UK-38,485 (50 mg/kg/d) given for 3 days, reduced basal TxB2 excretion by 75% and also attenuated (P less than .001) the AII-induced rise in MAP (11 +/- 2 mm Hg). However, when given 40 min before the AII infusion, UK 38,485 did not attenuate the pressor response. In separate groups of rats, the log dose-response curve for bolus intravenous injection of AII was shifted to the right by SQ-29,548 while that for PE was unaffected. IN CONCLUSION: 1) AII releases Tx; 2) Tx release is not secondary to hypertension; and 3) Tx can mediate up to two-thirds of the short-term pressor response to high-dose AII infusion. PMID- 2322438 TI - Cytosolic free calcium dependent regulation of osteoclast bone resorbing activity. AB - Osteoclasts are sensitive to KCl-induced depolarization and to increased extracellular calcium concentration, and respond to these treatments with cytosolic calcium increase. In this study we evaluated the possibility that these experimental conditions could affect osteoclast bone resorption. We found that, incubating osteoclasts with 3H-proline previously labeled bone particles the resorbing activity was inhibited by both depolarization and extracellular calcium concentration increase. The released radioactivity was, in fact, 48% and 52% respectively compared to the untreated cultures. These data demonstrated that cytosolic calcium increase is one of the messengers of the pathway that inhibits, in this condition, bone resorption. Furthermore, as in parathyroid cells, extracellular calcium acts with a negative direct feedback mechanism that controls osteoclast activity. PMID- 2322439 TI - [Splenic hematopoiesis in an experimental model of hemolytic anemia]. AB - The splenic hemopoiesis of rabbits, made anemic with acetylphenylhydrazine, and of control animals was investigated. Pieces of spleen of both groups were fixed in formalin and embedded in paraffin. Paraffin sections, cut 5-7 microns in thickness, were stained with hematoxylin-eosin, Giemsa, Perls' method for tissue iron (hemosiderin), and Perls-Chayen's method for iron stored in the hemoglobin. The erythroid line in the anemic rabbits, showed a marked increase of proerythroblasts and basophilic erythroblasts, while the poli and orthochromatic erythroblasts were less than their precursors. In contrast these cells were more than their precursors in control animals. There was no notable quantitative difference in the mature elements of this line in the anemic animals and in the controls. Megaloblasts and macroblasts were frequently observed in anemic spleens but they were practically absent in the controls. Regarding to other cell lineages, we noted in the anemic spleens many macrophages containing Perls and Perls-Chayen positive material and some megakaryocytes. Our results indicate that the APH-induced anemia stimulate the erythropoietic activity of the spleen in the rabbit, but the reversion of the amplification phase of the differentiation steps reveals that the erythropoietic process is ineffective. The presence of megalo- and macroblasts provide morphological evidence of dyserythropoiesis and the megakaryocytes suggest that under the anemia condition also the platelet regenerating process is stimulated. PMID- 2322440 TI - [Preliminary observation of blood cells and hematopoietic organs in Lutjanus herenbergi and Lutjanus flaviflammus]. AB - The morphology of differentiated and differentiating cells of the red and white series in Lutjanus herenbergi and in Lutjanus flaviflammus is described. Early stages of red and white blood cells may be found only in smears of hemopoietic organs. Polychromatic erythroblasts, myelocytes and lymphoblasts may also occasionally be found in blood smears. Mature blood cells may be found both in blood smears and in hemopoietic organs. Differential white cell counts seem to demonstrate that the granulocytic series elements are the most common leukocytes in blood smears. Almost all granulocytes may be classified in the first three Arneth classes. An analysis of hemopoietic organs in these species was also performed. It was found that the only organs carrying on a hemopoietic function are the kidney and the spleen. The kidney is essentially a site of granulocytic differentiation while the spleen is a lymphopoietic organ. An erythropoietic activity may generally be observed in the kidney although weak erythropoietic activity may at times be found in the spleen. PMID- 2322441 TI - [Glucose-6-phosphate dehydrogenase activity as a marker of resolution in the separation of rabbit erythroblasts according to their stage of maturation]. AB - The glucose 6 phosphate dehydrogenase (G6PD) activity of erythroblasts, separated at different advancing stages of development by the velocity sedimentation technique at unit gravity, shows a characteristic sigmoidal curve. The G6PD activity is high and constant in the dividing compartment, steeply declines between the polychromatic and the orthochromatic stage, and returns almost constant during the development from the orthochromatic to the reticulocyte stage. This report focuses on the possibility to use the G6PD activity curve to indicate a loss of resolution in the fractionation process. For this purpose two parameters of the graph were used: (h) which represents the distance between the two constant phases of the curve and (s) the slope of the decreasing part of the graph. In this view we have fractionated on a 400 ml linear gradient of sucrose (1%-2% in PBS), increasing amounts of bone marrow cells from anaemic rabbit. Suspensions of 100, 200, 350 and 700 millions of cells (25 ml in PBS) were separated in different experiments and the obtained G6PD activity curves were compared. We have seen that the two parameters h and s remained constant up to 200 millions of cells, while they declined markedly when the number of cells loaded on the gradient increased to 350 and 700 millions. The separated cells were grouped into three sets of fractions: fraction I with cells belonging to the high and constant phase of the graph, fraction II to the decreasing phase and fraction III to the low and constant activity phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322442 TI - [A study of the "outward potassium channel" (OPC) in the frog oocyte. I. A study of the "cell-attached" configuration]. AB - A single channel current was studied in the membrane of the immature oocyte of the european frog (Rana esculenta) by using the "patch clamp" technique in the "cell attached" configuration. Single channel activity appeared as short outward currents when membrane potential was made positive inside; full activation required seconds to be complete, no inactivation being appreciable. Deactivation (or current block) upon membrane repolarization was so fast that no inward current could be detected in any case. The reversal potential, estimated by interpolating the I/V diagrams, was -30 mV using standard Ringer as electrode filling solution, and the elementary conductance was 95 pS. Neither reversal potential nor elementary conductance were affected by removal of external Ca2+ (Mg2+ or Ba2+ substitution) or external Cl- (methanesulphonate substitution). The reversal potential moved towards positive potentials by substituting external Na+ with K+, the magnitude of the shifts being consistent with a ratio PK/PNa = 6.4. A distinctive property of the current/voltage relation for this K-current is its anomalous bell-shape, the outward current displaying a maximum at membrane potentials around 75 mV with standard Ringer as electrode filling solution and tending to zero with more positive potentials. PMID- 2322443 TI - [A study of the "outward potassium channel" (OPC) in the frog oocyte. II. A study of the "inside-out" configuration]. AB - The single K-channel current reported in a previous note was also studied in "outside-out" conditions. The electrode filling solutions used for the "cell attached" experiments faced in this case the intracellular side of the membrane patches, the extracellular side facing the bath saline, i.e. Ringer standard. The most significant observations were obtained with filling solutions with varying proportions in K/Na concentrations solutions. In the absence of Na+ ([K+] = 110 mM), the elementary conductance was still around 90 pS and the I/V diagram was again somewhat bell shaped, though the distinctive reduction of the elementary conductance began at more positive potentials (+110 mV). No inward current could be detected upon membrane repolarization also in this case. The rectification became less evident and conductance increased with increasing Na+ concentration in the filling solution, until the I/V curve became a linear one and conductance was 270 pS with standard Ringer. Distinct inward elementary currents were evident upon repolarization in these conditions. Thus a complex interaction between Na+ and K+ takes place for conduction through the outward K channel in the frog oocyte, both cations probably competing for at least one active site inside. Another interesting observation concerns the process of gating of the OPC: the open times of the elementary currents were in fact much greater in outside out experiments as compared to cell-attached experiments, probably due to the presence of Ca++ in contact with the inner membrane side. Even increasing Na+ concentration prolonged the open time duration. The gating of the OPC in the membrane was not only voltage dependent, but also Ca++ and Na+ dependent. PMID- 2322444 TI - [Augmentation of the biodisposition of simple sugars from sorghum biomass mediated with biotechnologic processes]. AB - The results of the enzymatic hydrolysis of pectin, hemicellulose and cellulose in the biomass of sweet sorghum (Sorghum vulgare var. saccharatum, L.) are reported. Some commercial enzymatic preparations were used: Maxazym CL 2000 (with prevailing cellulase activity), Rapidase C 80 (with prevailing pectinase activity) Rohament PC (mainly with pectinase and cellulase activities) and Rohament O (mainly with pectinase and hemicellulase activities). The treatment with Rohament PC, Rohament O and Rapidase C 80 gives an increase of the glucose content higher than the effect induced by Maxazym CL 2000. On the other hand, the cellulase and pectinase combined treatment (Maxazym CL 2000 + Rapidase C 80 or Maxazym CL 2000 + Rohament O) shows a good synergistic effect in the degradation of the plant cell wall cellulosic material. PMID- 2322445 TI - [Essential polyunsaturated nutrients in the development of rat striated muscle]. AB - The striated muscle of the rat demonstrates, throughout the growth, an increase of the short C-chain saturated and of the mono-unsaturated fatty acids; a decrease of the saturated and poly-unsaturated fatty acids and shows a great quantity of the hyper-unsaturated (eicosapentaenoic and docosaesaenoic) fatty acids. The supplementation with linoleic and alpha-linolenic acids induces some effects of stabilization of the poly-unsaturated fatty acids in the grown-up and adult rat. PMID- 2322446 TI - [Fatty acids in striated muscle of the rat treated with toxic radicals]. AB - In the striated muscle of the growing and adult rat CCl4 poisoning increases all the saturated fatty acids and decreases the mono-unsaturated and arachidonic fatty acids. The supplementation with poly-unsaturated fatty acids increases, in rat's striated muscle, mono-unsaturated acids and decreases saturated, arachidonic, docosaexahenoic acids. PMID- 2322447 TI - [Stapedo-ovalar ankylosis: histomorphologic patterns]. AB - This study reports the results of the histo-pathological investigation on the stapes (fragments or complets) of 46 patients (34 females and 12 males) with clinical diagnosis of stapedial otosclerosis and submitted to stapedectomy. Otospongiotic and otosclerotic areas have been found only in some cases; more frequently, erosion cavities filled with fibrous tissue and round-cells infiltration with lymphocytes and/or macrophages have been seen. Osteoclasts were observed only in few cases. Blue mantles have been observed in about half of the cases. Our findings show that non specific chronic inflammation should be more frequent than otospongiosis or otosclerotic foci, and indicate that a phlogosis could be the pathogenetic agent of this disease. This conclusion is in agreement with our previous research, and has been recently confirmed by the observations in stapes of otosclerotic patients of viral antigens and antibodies. PMID- 2322448 TI - Differences between male and female protogonia in chick embryos before sex differentiation of the gonads. AB - The sex of chick embryos is diagnosed by cyto-karyological methods on skin fragments of 2-7 days' incubation before gonadal sex differentiation. In 44 males and 42 females statistical analyses have been made of the number and dimension of the germ cells, and of the volume of the gonadal primordia. Moreover an ultrastructural study has been made on the germ cells colonizing the genital ridges (70-hours of incubation). Early differences between the sexes have been found regarding: earlier numerical increase of CGs in the left gonadal primordium of the females; larger primordial germ cells in the female; the same cytological characteristics at ultrastructural level. PMID- 2322449 TI - A simple screening method for transgenic mice using the polymerase chain reaction. PMID- 2322450 TI - A rapid method for characterizing transgenic mice. PMID- 2322451 TI - A quantitative assay for beta-D-glucuronidase (GUS) using microtiter plates. PMID- 2322452 TI - A simple, inexpensive gel stripper. PMID- 2322453 TI - A strategy for single site PCR amplification of dsDNA: priming digested cloned or genomic DNA from an anchor-modified restriction site and a short internal sequence. AB - Amplification of dsDNA by polymerase chain reaction (PCR) has been limited to those instances in which segments of known sequence flank the fragment to be amplified. A strategy for the PCR amplification of cloned or genomic dsDNA that necessitates sequence information from only a single short segment (single site PCR) has been devised. The region of known sequence may be located at any position within or adjacent to the segment to be amplified. The basic procedure for amplification consists of 1) digestion of dsDNA with one or more restriction enzymes, 2) ligation with a universal anchor adaptor and 3) PCR amplification using an anchor primer and the primer for the single site of known sequence. The anchor adaptor is designed in such a way as to facilitate the amplification of only those fragments containing the sequence of interest. We have demonstrated the utility of this technique by specifically amplifying and directly sequencing antibody variable region genes from cloned dsDNA and from genomic DNA. PMID- 2322454 TI - Comparison of particulate 3,3',5,5'-tetramethylbenzidine and 3,3' diaminobenzidine as chromogenic substrates for immunoblot. AB - In horseradish peroxidase (EC: 1.11.1.7)-dependent immunoblot assays, particulate 3,3',5,5'-tetramethylbenzidine (TMB) is shown to be a more efficient immunoblot substrate than the standard substrate 3,3'-diaminobenzidine (DAB), because TMB is easily prepared, stable, and less carcinogenic than is DAB. Assays of antibody in a serially diluted human immunodeficiency virus (HIV) control serum (CDC reference CAT# VS2151) have the same sensitivity limits with both DAB and TMB (1:312,500). Complete, working substrate solutions of H2O2/TMB/enhancer and of H2O2/DAB were stored at room temperatures and at 48 degrees C respectively. Periodic tests showed the TMB substrate system to be functional after four weeks at 48 degrees C and after eight weeks at room temperature, while the DAB system was functional after one week at 48 degrees C and after four weeks at room temperature. The stability, safety, and convenience of the commercially available TMB kits make this substrate ideal for immunoblot tests. PMID- 2322455 TI - A double-labeling method for measuring induction of protein phosphorylation. AB - Protein phosphorylation is widely believed to play a regulatory role in signal transduction, mitosis, cell proliferation, cell motility, cell shape, gene regulation, and many other cellular processes. Thus, the quantitation of phosphorylation of specific cellular proteins may provide insight into the mechanisms by which phosphorylation is employed in regulation. Moreover, identification of phosphorylation substrates of various cellular kinases provides an important first step in determining their role in cellular regulation. However, accurate measurement of the differential phosphorylation of cellular proteins under different physiological conditions is often difficult to achieve. To address this problem, we have developed an in vivo double-labeling protocol (utilizing [3H]-, [14C]-, or [35S]-radiolabeled amino acids and [32P] orthophosphate) that allows the quantitation of the amount of specific phosphorylation of a given protein from densitometric analysis of autoradiograms of polyacrylamide gels. This double-labeling strategy provides a means of quantitating the phosphorylation of individual biosynthetically labeled proteins. This method can be used in the analysis of immunoprecipitated proteins, proteins from subcellular fractions, such as nuclei or selected membrane fractions, or even total cellular proteins displayed on two-dimensional gels. PMID- 2322456 TI - Quality control test for immunoreactivity of radiolabeled antibody. AB - A rapid method for the measurement of the immunoreactive fraction of a radiolabeled monoclonal antibody or antibody fragment has been developed. This may be used as a quality control test prior to patient administration of the radiolabeled antibody preparation. The test employs solid phase antigens and the assay is conducted under conditions of antigen excess. Assay parameters have been evaluated and a standardized procedure has been developed. The assay has been compared to a standard extrapolation method and found to give approximately the same result. The test has been used on four different radiolabeled antibodies currently in clinical trials in patients with colorectal cancer. Mean immunoreactive fractions for these radiolabeled antibodies ranged from 35 to 65% and the variability of the immunoreactive fraction ranged from 140 to 240% for different antibodies. We conclude that the quality, defined as the immunoreactive fraction, of radiolabeled antibodies is both low and highly variable, indicating the need for a quality control test of these radiopharmaceuticals in the clinic prior to patient administration. PMID- 2322457 TI - Antibody production and growth of mouse hybridoma cells in Nutridoma media supplements. AB - Traditionally, cell culturists have relied upon the addition of serum to culture medium for the growth and maintenance of cell lines. However, many aspects of the use of serum in tissue culture are problematic. Cell culture supplements that circumvent the need for serum are readily available and provide a consistent protein composition. This defined environment allows the antibody to be more easily purified from culture supernatants. Nutridoma media supplements were formulated to support the growth of lymphoblastoid cells in a defined culture environment. In this study, Nutridoma media supplements were tested in parallel with serum-containing cultures to determine if Nutridoma supplemented medium is effective in supporting hybridoma cell growth and antibody production in three hybridoma cell lines. Data, based on cell growth and antibody production, show the importance of basal media selection when serum is replaced with Nutridoma media supplements. SDS-PAGE results show that cell supernatants from Nutridoma supplemented cultures contain very few contaminating proteins. PMID- 2322458 TI - The effects of N-cadherin misexpression on morphogenesis in Xenopus embryos. AB - N-cadherin is a calcium-dependent, cell adhesion molecule that has been proposed to play a role in morphogenesis in vertebrate embryos. Throughout early neural development, N-cadherin is expressed during the morphogenetic changes that occur when ectoderm, in response to neural induction, forms a neural plate and tube. To study the role of N-cadherin in these processes, cDNA clones encoding Xenopus laevis N-cadherin were isolated and used to study the expression of N-cadherin in frog embryos. These studies showed that N-cadherin RNA is not expressed at detectable levels in early cleavage embryos or in isolated ectoderm in the absence of neural induction. However, N-cadherin RNA rapidly appeared in ectoderm exposed to a heterologous neural inducer, indicating that N-cadherin expression, as an early response to induction, precedes the morphogenetic events associated with early neural development. The role of N-cadherin in these morphogenetic events was studied by ectopically expressing N-cadherin in the ectoderm of embryos prior to induction. The ectopic expression of this protein in ectoderm led to the formation of cell boundaries and to severe morphological defects. These results are consistent with the hypothesis that the morphogenetic changes associated with early neural development are controlled, in part, by the induced expression of N-cadherin in the neural plate. PMID- 2322459 TI - Early axonal contacts during development of an identified dendrite in the brain of the zebrafish. AB - We have identified the initial synaptic contacts made onto the Mauthner (M) cell, an identified neuron that arises during early development of the zebrafish hindbrain. The contacts are made by a small bundle of pioneering trigeminal sensory axons onto the M cell soma before it forms dendrites. The sensory bundle is then partially enveloped by the M cell. The lateral dendrite appears at about the site of the contact, and eventually the trigeminal inputs are shifted to its trunk. As the dendrite elongates, other sensory contacts are made on its distal regions, sequentially from the acoustico-vestibular nerve and the lateral line nerves. To learn whether the earliest inputs induce the initial outgrowth of the M cell dendrite, we ablated the trigeminal neurons by laser irradiation before they contacted the M cell. Morphogenesis of the M cell, including its dendrite, appeared normal. PMID- 2322460 TI - Feedback inhibition by calcium limits the release of calcium by inositol trisphosphate in Limulus ventral photoreceptors. AB - Injection of inositol 1,4,5 trisphosphate (InsP3) into Limulus ventral photoreceptors elevates the concentration of intracellular calcium ions and as a consequence depolarizes the photoreceptor. This InsP3-induced elevation can be inhibited by a prior injection of calcium or InsP3 delivered 1 s earlier. Recovery from this inhibition has a half-time of between 1.5 and 5 s at 20 degrees C. Calcium released by InsP3 therefore inhibits further release of calcium from InsP3-sensitive calcium stores. This feedback inhibition may protect the calcium stores from depletion during prolonged bright illumination. Feedback inhibition, rather than periodic depletion of calcium stores, may also underlie the oscillatory bursts of InsP3-induced calcium release that have been observed in many cell types. PMID- 2322461 TI - Regulation of turnover and number of acetylcholine receptors at neuromuscular junctions. AB - The number and metabolic stability of acetylcholine receptors (AChRs) at neuromuscular junctions of rat tibialis anterior (TA) and soleus (SOL) muscles were examined after denervation, paralysis by continuous application of tetrodotoxin to the nerve, or denervation and direct stimulation of the muscle through implanted electrodes. After 18 days of denervation AChR half-life declined from about 10 days to 2.3 days (TA) or 3.6 days (SOL) and after 18 days of nerve conduction block to 3.1 days (TA). In contrast, the total number of AChRs per endplate was unaffected by these treatments. Denervation for 33 days had no further effect on AChR half-life but reduced the total number of AChRs to about 54% (SOL) or 38% (TA) of normal. Direct stimulation of the 33-day denervated SOL from day 18 restored normal AChR stability and counteracted muscle atrophy but had no effect on the decline in AChR number. The results indicate that motoneurons control the stability of junctional AChRs through evoked muscle activity and the number of junctional AChRs through trophic factors. PMID- 2322462 TI - A cell type-preferred silencer element that controls the neural-specific expression of the SCG10 gene. AB - SCG10 is a growth-associated protein that is expressed early in the development of neuronal derivatives of the neural crest. We describe here the isolation of the SCG10 chromosomal gene and the identification of regulatory regions that control its expression. The SCG10 transcription unit spans approximately 40 kb. Like other neural-specific genes, SCG10 contains multiple transcription initiation sites. The gene contains a constitutive enhancer-like element in the promoter-proximal region and a silencer located farther upstream. This silencer preferentially suppresses the activity of the enhancer in nonneuronal cells. Furthermore, the silencer is able to confer such preferential suppression upon a heterologous promoter in an orientation-independent manner. These data suggest that the expression of SCG10 in neuronal cells depends predominantly upon specific derepression. PMID- 2322463 TI - Analysis of SCG10 gene expression in transgenic mice reveals that neural specificity is achieved through selective derepression. AB - SCG10 is a neural-specific, growth-associated protein that is broadly expressed in the embryonic central and peripheral nervous systems. Transgenic mice harboring a chimeric gene containing 4 kb of SCG10 5' flanking DNA fused to the bacterial CAT gene exhibit expression in brain but not in nonneuronal tissues. A low level of expression is detected in adrenal gland as well, consistent with the behavior of endogenous SCG10. Such a transgene is also activated at the same relative stage of embryonic development as its endogenous counterpart. Deletion of the 5'-most 3.7 kb of SCG10 sequence yields deregulated expression of the transgene in numerous nonneuronal tissues, although expression remains highest in brain. In contrast to other tissue-specific genes, therefore, the specificity of SCG10 expression appears to be achieved predominantly through selective repression in nonneuronal tissues. PMID- 2322464 TI - Parallel pathways for habituation in repetitively stimulated PC12 cells. AB - Habituation was investigated in neuronally differentiated PC12 cells by measuring the decrease in cellular secretion of norepinephrine with repetitive stimulation by either membrane depolarization or acetylcholine. When these two types of repetitive stimulation were applied to the same cells, habituation occurred independently to each, showing that two pathways for habituation can be utilized simultaneously in single cells. The two pathways apparently process stimuli in parallel, without competition between common intermediates. PMID- 2322465 TI - Purification and characterization of a trophic factor for embryonic peripheral neurons: comparison with fibroblast growth factors. AB - The validation of NGF as a physiologically important neurotrophic factor has led to intense efforts to identify novel polypeptide growth factors for neurons. We report here the details of a greater than 80,000-fold purification of a neurotrophic molecule, referred to as growth-promoting activity (GPA), from chicken sciatic nerves. The final product of the purification migrated as a protein band of 21.5 kd, its apparent pI was approximately 4.8, and the ED50 of the most active preparation was approximately 10 pg/ml. Amino acid sequence of a proteolytic digestion fragment of GPA revealed homology with the recently published sequences for rabbit and rat sciatic nerve CNTF. Thus this molecule may be the chicken form of CNTF. Analysis of the specificity of action of GPA showed that, in addition to E8 ciliary ganglion neurons, the factor was able to support short-term survival of E8 dorsal root ganglion and E12 sympathetic neurons. This range of specificities of biological action was also seen with both acidic and basic FGF in the presence of heparin. The biological activity of GPA differed from that of FGF in that it was not potentiated by heparin and did not stimulate mitogenesis in chick fibroblasts. PMID- 2322466 TI - Murine lung immunity to a soluble antigen. AB - Although it is known that soluble antigen is immunogenic when deposited in the respiratory tract, less is known about lung immunity to soluble antigen than is known about lung immunity to particulate antigen. To test the hypothesis that soluble antigen triggers antigen-specific immunity in the respiratory tract in a fashion similar to that reported for particulate antigen, we examined the development of local and systemic immunity in C57BL/6 mice after intratracheal (i.t.) instillation of a soluble, large molecular weight protein neoantigen, keyhole limpet hemocyanin (KLH). Specific anti-KLH IgG and IgM first appeared in the sera of mice on day 7 after primary immunization by i.t. instillation of KLH, with specific serum antibody concentrations remaining elevated at day 11. Cell populations prepared from lung-associated lymph nodes of immunized mice released specific anti-KLH IgG and IgM in vitro; peak levels were obtained from cells isolated 7 days after antigen instillation, with levels of specific antibody released by cells isolated on days 9 and 11 decreasing markedly. Cultured spleen cells obtained from mice after primary immunization released only low levels of specific IgM, and no specific IgG. No specific antibody was released by cell populations derived from the lungs of animals undergoing primary immunization. When presensitized mice were given an i.t. challenge with KLH, responses differed markedly from those following primary immunization. Lung-associated lymph node cell populations from challenged mice released greater amounts of specific antibody earlier than did cell populations from mice undergoing primary immunization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322467 TI - The effects of activated eosinophils and neutrophils on guinea pig airway epithelium in vitro. AB - Epithelial shedding is a characteristic feature of asthmatic airways and has been attributed to eosinophil products. We have examined the interaction of purified intraperitoneal guinea pig eosinophils with or without platelet-activating factor (PAF, 10(-7) M) or lyso-PAF (10(-7) M) with guinea pig tracheal epithelium in vitro. At 0, 4, 14, and 24 h, the percentage of ciliation of the tracheal circumference (CTC) was measured by light microscopy and the ciliary beat frequency (CBF) by photometry. PAF-activated eosinophils (50 x 10(6) cells/ml) disrupted the epithelium, mean CBF and CTC being reduced by 77.8 +/- 5.8% (mean +/- SEM; P less than 0.001 versus control) and 94.2 +/- 1.4% (P less than 0.001) over 24 h, respectively. PAF (10(-7) M) alone had no significant effect. Lyso-PAF with eosinophils (50 x 10(6) cells/ml) also reduced mean CBF and CTC but to a lesser extent. Eosinophils alone also led to a reduction of 36.2 +/- 11.4% in mean CBF and 53.0 +/- 15.5% in CTC, but these changes were not significant. The PAF antagonist, WEB 2086 (10(-6) M), significantly inhibited the mean CBF and CTC reduction due to PAF-activated eosinophils by 61.5 +/- 17.2% (P less than 0.01) and 20.8 +/- 6.5% (P less than 0.05), respectively. In addition, catalase (1,125 U/ml) partially inhibited the mean CBF and CTC reduction induced by PAF-activated eosinophils. Intraperitoneal neutrophils (PMN) (50 x 10(6) cells/ml) also disrupted epithelium but to a lesser extent (24-h reduction: 34.2 +/- 12.7% for mean CBF and 60.2 +/- 13.2% for CTC, respectively). Stimulation with PAF (10(-7) M) had no further effect. Marked exfoliation of the epithelial layer was observed after 14 h of incubation with activated eosinophils. We concluded the PAF activated eosinophils are capable of grossly disrupting ciliated epithelium and may contribute to epithelial damage observed in asthma. PMID- 2322468 TI - The conductance of cultured epithelial cell monolayers: oxidants, adenosine triphosphate, and phorbol dibutyrate. AB - Oxidants are one class of inflammatory molecules that may contribute to an increase in epithelial permeability to water and solutes that commonly occurs during acute inflammation. We and others have observed that oxidants reversibly alter the paracellular conductance of Madin Darby canine kidney epithelial (MDCK) cell monolayers. The mechanism by which oxidants reversibly alter MDCK monolayer conductance is not yet fully understood. Some investigators have suggested that oxidants might alter MDCK monolayer paracellular conductance by depleting adenosine triphosphate (ATP) in the cells. When we exposed MDCK cells to doses of oxidants that increased monolayer paracellular conductance in earlier studies, ATP was depleted within 10 min. However, when ATP was depleted to similar levels with an inhibitor of glycolytic ATP production, 2-deoxy-D-glucose (DOG), monolayer paracellular conductance was not increased. Severe ATP depletion with DOG and the mitochondrial metabolic inhibitor, antimycin A (AA), had very limited, ATP-independent effects on paracellular conductance. As an alternative explanation for the effects of oxidants on MDCK monolayer paracellular conductance, we had reported that oxidants increased production of inositol phosphates and diglycerides in MDCK cells. Synthetic diglyceride and phorbol dibutyrate (PDBU) increased MDCK monolayer conductance to ions and mannitol in earlier studies. When MDCK cell ATP was depleted with DOG (to the level caused by oxidants), the increase in conductance following PDBU was not different from that observed in control cells. More severe ATP depletion, with DOG and AA, prevented the increase in conductance following PDBU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322469 TI - Isolation and characterization of mucin from the serum of cystic fibrosis patients. AB - Using monoclonal antibody 19-9, elevated levels of the sialyl Lea antigen (NeuAc alpha 2-3Gal beta 1-3[Fuc alpha 1-4]GlcNac beta 1-3R) are detected in serum from most cystic fibrosis patients. We now report further characterization of the serum antigen and evidence that it is on a mucin glycoprotein and not on glycolipids. The antigen has an apparent molecular weight greater than 2 X 10(6) by gel filtration on Sephacryl S-400. On density gradient centrifugation, the antigen has a density of 1.54 g/ml in cesium chloride and 1.42 g/ml in cesium chloride/4 M guanidine HCl. Immunostaining with monoclonal antibody 19-9 of lipid extracts from cystic fibrosis patient serum and erythrocytes does not detect any antigen on glycolipids. The antigen was purified by gel filtration and density gradient centrifugation. After tritium labeling of the sialic acid residues, sodium dodecyl sulfate gel electrophoresis separates two subunits with apparent molecular weights of 200,000 and 400,000. All of the labeled sialic acid is released as low molecular weight oligosaccharides after mild alkaline borohydride degradation. The purified antigen contains fucose, galactosamine, glucosamine, and galactose but no mannose and is enriched in the amino acids threonine, serine, glycine, proline, and alanine. The purified antigen binds several antibodies recognizing epitopes common to many mucins. Thus, the physical, biochemical, and immunochemical properties of the purified antigen indicate that the sialyl Lea antigen is present on mucins in the serum of cystic fibrosis patients. PMID- 2322470 TI - Crohn's disease in the Japanese is associated with the HLA-DRw53. AB - The association of Crohn's disease (CD) with the HLA system was investigated in Japanese patients by serological and genomic methods. HLA antigens were typed in 30 unrelated Japanese patients with CD and 54 healthy controls. The frequencies of HLA-DR4, DRw53 and DQw3 antigens were increased in CD (76.7, 86.7 and 80.0%) compared with controls [37.0%, p corrected (pc) = 0.007; 52.9%, pc = 0.001; 52.0%, pc = 0.009]. DQw7 and DQw8 antigens, the new split antigens of DQw3 produced by the TA10 antibody and linked to the DR4 and DRw53 antigens, were not significantly different in the DQw3-positive CD and controls. Class I antigens were not significantly different in the CD and controls. HLA-DR-B and DQ-B probes were used to study PstI-generated restriction fragment length polymorphism (RFLP) in CD and controls. The DRw53-specific PstI DR-B 2.6-kb fragment was increased in CD (88.0%) compared with controls (37.5%, pc = 5.6 X 10(-4)). The PstI DR-B 3.2 kb fragment was also increased in CD (80.0%) compared with controls (35.0%, pc = 5.6 X 10(-3)). It is reasonable to infer that the DRw53 is the most important susceptibility antigen in Japanese CD. The subtypes of the DR4 were determined by the hybridization of the DQ-B probe. The DQ-B PstI fragment patterns were not different in CD and controls. PMID- 2322471 TI - H-2 class I gene analysis in 3-methylcholanthrene-induced murine fibrosarcomas. AB - The objective of our study was to determine whether and how frequently MHC class I gene alterations occur in fibrosarcomas induced in BALB/c mice by the carcinogen 3-methylcholanthrene (3-MCA). Southern blot was performed to analyze the genomic organization of class I genes in a panel of twenty tumors of different immunogenic strength used at early in vivo passages. Our results rule out the presence of gross rearrangements or deletions in the H-2 class I genes of the tumors tested and indicate that the frequency of detectable class I alterations giving rise to restriction fragments length polymorphism (RFLP) should be very low. PMID- 2322472 TI - DNA fingerprinting in a random sample of Japanese population with the minisatellite probe MZ 1.3. AB - The DNA fingerprinting analysis with minisatellite probe MZ 1.3 with a nonisotopic technique is described. We determined a random sample of Japanese population with 36 samples. PMID- 2322473 TI - Amino acid substitutions determining G3m(g5). AB - Amino acid substitutions specific for allotypic G3m(g5) marker were studied by sequence analysis of the C-terminal BrCN peptides of myeloma protein Ba [G3m(g5+)] and Bu [G3m(g5-)]. The results indicate that arginine and tyrosine at position 435 and 436 are responsible for the specificity. Two substitutions of IgG3 Bu [G3m(b1, b3)] and IgG3 Jir [G3m(b3,s,t)] [Matsumoto et al.: J. Immun. 131: 1865, 1983], in the same positions are arginine-phenylalanine and histidine tyrosine, respectively. Affinity chromatographic data of modified IgG3 proteins show that the tyrosine residue at position 436 associated with phenylalanine at position 124 of protein A-B fragment plays a role in the interaction. The differences in the yields between IgG3s carrying various haplotypes on Protein A Sepharose affinity chromatography [Ito et al.: Proc. Japan Acad. 56B: 226, 1980] are also explained through this chromatography and also by the configuration of the residues in tertiary structure [Deisenhofer: Biochemistry 20: 2361, 1980]. PMID- 2322474 TI - [Changing health behavior]. AB - This paper describes the process of changing health behavior or lifestyle experienced by individuals who already have succeeded in changing smoking habits, nutrition habits and/or exercise habits. Eighteen persons were interviewed about their experiences. The process starts with an awareness of a concrete threat to health or with a dissatisfaction with the self. Social support, physical and psychological feed-back are the most important helping factors and loneliness, bad models and conflict in given information are threatening factors. The conclusion is that health care professionals play an important part in the process of change if the life situation and the needs of the individual are understood and if right kind of help is offered. PMID- 2322475 TI - [Development and evaluation of a curriculum for the education of nurses: evaluation of students and their acquisition of the fundamentals of nursing]. AB - A theoretical framework is put forward for the structure of a nursing curriculum and factors pointed out which should be born in mind when planning, implementing and evaluating such a curriculum. The data were acquired of a questionnaire sent to 321 students after their first term at Finnish language schools of nursing. The students' evaluations suggested that the descriptions of the aims of the fundamentals of nursing were of a high communicative standard, and in their opinion they had reached the objectives of the course sufficiently well in the field of the patient's basic physical needs, whereas they had been less successful at appreciating patients' psychological and social needs at that stage in their education. The replies also demonstrate that no connection is normally perceived between the achievement of learning goals in the field of physical needs and the methods used in the teaching of this. A student-centred teaching method was the preferred approach when learning to listen to the patient's needs. PMID- 2322476 TI - [The concept of man in nursing education: evaluation of the students' answers to the exam questions in nursing]. AB - The purpose of the study was to describe the concept of man in nursing education. The data consisted of the nursing students' answers to the summative exam questions in seven courses in nursing. The total number of answers in the study was 202. The data was analyzed by the method of content analysis. Four dimensions of the concept of man were formed on the basis of the theoretical background: the holistic concept of man, the reduced concept of man, man as an active subject, man as a passive object. From the answers 40% described man as a holistic, active subject and 30% as a reduced, passive object. Man as a holistic, passive object was identified in 16% of the answers and as a reduced, active subject in the rest. The holistic concept of man was expressed as a bio-psychosocial wholeness. The reduced concept meant that man was described mostly as a biological organism. The activity of man was described as concrete activity, man was not described as a decision maker. PMID- 2322478 TI - American Society for Laser Medicine and Surgery, tenth annual meeting. Nashville, Tennessee, April 6-8, 1990. Abstracts. PMID- 2322477 TI - Rogers' theory: research to practice. PMID- 2322479 TI - 'MGDS examination'. PMID- 2322480 TI - 'The unpredictability of impacted third molar development'. PMID- 2322481 TI - 'Anaesthesia, analgesia and sedation--the key to successful dentistry'. PMID- 2322482 TI - 'The orthodontic skill mix in Sweden'. PMID- 2322483 TI - Examination charge. PMID- 2322484 TI - 'The capitation study'. PMID- 2322485 TI - 'Changing perceptions of the requirements of cavity preparations'. PMID- 2322486 TI - 'Orthodontic research'. PMID- 2322487 TI - 'Reasonable remuneration?'. PMID- 2322488 TI - Methadone and caries. PMID- 2322489 TI - Intra-oral softening of bovine enamel exposed to Lycasin and sucrose. AB - In previous experiments, the sucrose substitute Lycasin has been shown to possess low acidogenic potential. Intra-oral cariogenicity tests were carried out in humans to explore the enamel softening effects of Lycasin, using sucrose and saline as controls. The results confirmed that Lycasin would be preferred to sucrose as a sweetener for confections and medicines, although some softening of enamel by Lycasin was evident when compared to the saline controls. The magnitude of this enamel change was small and of doubtful clinical significance. PMID- 2322490 TI - Heck's disease. AB - The clinical and histological findings in two adult caucasians with focal epithelial hyperplasia (Heck's disease) are described. The literature concerning this rare condition is reviewed. PMID- 2322491 TI - Treatment of Class II malocclusions with removable appliances. Part 3. Functional appliance therapy. AB - Functional appliance therapy can give good correction of Class II division 1 malocclusion. The keys to success are careful case selection and use of appliances that are active enough to work, but comfortable enough to be worn for 14 hours each day. Patient motivation is also an important factor. PMID- 2322492 TI - Dental care in Papua New Guinea. AB - In August, 1989, I visited Papua New Guinea for my elective. During four weeks, in a land sometimes referred to as 'The Last Unknown', I gained an insight into some of the problems of providing primary dental care. PMID- 2322493 TI - AIDS and children. PMID- 2322494 TI - The discrimination between nickel-sensitive and non-nickel-sensitive subjects by an in vitro lymphocyte transformation test. AB - A lymphocyte transformation test (LTT) was able to distinguish between nickel sensitive subjects and non-nickel-sensitive controls. Sixty-one out of 66 (92%) nickel-sensitive subjects had positive stimulation indices in 6- and/or 7-day assays using 5 micrograms/ml of nickel sulphate, whereas none of the 43 controls gave positive results. Stimulation indices were not enhanced by the patch testing of subjects to nickel before performing the LTT. A weak correlation was seen between the results of the LTT and the macroscopic degree of patch-test reactivity. The concentration of nickel sulphate used (5 micrograms/ml) did not have a significant non-specific mitogenic effect. PMID- 2322495 TI - Nickel-sensitive patients with vesicular hand eczema: oral challenge with a diet naturally high in nickel. AB - Oral challenge with nickel sulphate indicated that vesicular hand eczema in nickel-sensitive patients may be exacerbated by nickel occurring naturally in the diet. Twelve nickel-sensitive females with vesicular hand eczema were challenged with a supplementary high nickel diet for 4 days in a single-blind cross-over study. The diet had about five times the average nickel content of the daily Danish diet. An aggravation of the hand eczema was observed in six out of 12 patients on day 4 after the start of the challenge. By day II, the hand eczema was worse in 10 out of 12 patients, and remained unchanged in two. PMID- 2322496 TI - HLA-A, B, C and DR antigens in nickel contact sensitivity. AB - The relationship between HLA antigens (A, B, C and DR) and nickel contact sensitivity was examined in 54 patients with contact allergy, as confirmed by an unequivocal positive patch-test reaction only to nickel. A control group was 320 healthy blood donors from the same geographical area as the patients. The HLA-A, B, C and DR antigens were typed using standard serological methods. HLA typing revealed a significant increase of HLA-DRw6 antigen in the patient group (corrected P less than 0.025) and the relative risk for patients with DRw6 to develop nickel sensitivity was 3.32. PMID- 2322497 TI - Immunohistochemical identification of interleukin I alpha and beta in human eccrine sweat-gland apparatus. AB - Bouin-fixed paraffin sections or acetone-fixed cryostat sections were labelled with the avidin-biotin complex (ABC) or peroxidase-antiperoxidase (PAP) method using three monoclonal antibodies (MAbs) and two polyclonal antisera to human recombinant interleukin I beta (IL-I beta) and three polyclonal antisera to human recombinant interleukin I alpha (IL-I alpha). In the secretory coil both IL-alpha and beta were detected in the clear, but not in the dark cells. Both luminal and basal cells of the coiled and straight ducts expressed IL-I alpha and beta, the IL-I labelling being more intense in the luminal cells. IL-I was not usually detected in the initial portion of the intraepidermal eccrine sweat duct, whereas intense labelling was seen in the upper part including through the stratum corneum. In skin biopsies of the palm, taken after exercise, there was only faint IL-I labelling of the secretory cells, whereas the luminal cells of the dermal ducts showed intense labelling for both IL-I alpha and beta. In the acrosyringium, exercise did not alter the pattern for IL-I alpha and beta, except that in the palm, some of the antibodies to IL-I beta produced a more intense immunolabelling of the acrosyringeal cells. This study identifies a distinct and similar distribution of the two forms of IL-I throughout the eccrine sweat-gland apparatus and indicates that part of the IL-I epidermal pool originates from the sweat. PMID- 2322498 TI - Thermographic assessment of patch-test responses. AB - Infra-red thermography was used to quantify, at patch test sites, the allergic responses to experimental preparations of nickel sulphate and primary irritant responses to sodium lauryl sulphate in small groups of volunteers. The technique was also used to assess the patch-test responses in a much larger group of patients who had undergone routine patch testing for contact allergy with a wide range of test substances and among which there were large numbers of allergic, irritant and equivocal reactions. Thermographically, when compared to the surrounding normal skin surface, the sites of allergic reactions appeared as hot areas, the temperature and area of which were apparently dependent on the severity of the response. For allergic responses, there was a good correlation between the clinical assessment and either of two thermographic parameters, temperature and area of involvement. Compared with an aqueous solution of nickel sulphate, 'poor' formulations of the allergen, such as a suspension in soft paraffin base, elicited smaller and cooler reactions. Irritant reaction sites were not 'hot' and the temperature at such sites was no different from that of the surrounding normal skin. Infra-red thermography is a convenient non-invasive technique which apparently can be used to discriminate between irritant and allergic responses and to quantify the latter type of response. PMID- 2322499 TI - The influence of microwave radiation on transdermal delivery systems. AB - It has been alleged that the exposure of a transdermal delivery system to leakage of microwave radiation from a domestic microwave oven can result in the user receiving a second-degree burn in the area of the patch. Several transdermal delivery systems were exposed to microwave radiation from an Electro Medical Supplies Microtron 200 microwave diathermy unit. Temperature rises of up to 2.2 degrees C were recorded at a maximum power density of 800 W/m2. These temperature rises were considered insignificant compared to that required to produce a burn. The exposure of transdermal delivery systems to a microwave diathermy field or lower level leakage radiation from a microwave oven is unlikely to cause direct thermal injury to the wearer. PMID- 2322500 TI - Uroporphyrinogen decarboxylase deficiency in hepatoerythropoietic porphyria: further evidence for genetic heterogeneity. AB - Catalytic and immunoreactive erythrocyte uroporphyrinogen decarboxylase was measured in a woman with hepatoerythropoietic porphyria (HEP). The uroporphyrinogen decarboxylase activity was 24% of the mean value for normal controls and the concentration of the immunoreactive enzyme (106 ng/mgHb), measured with the rocket immunoelectrophoresis technique, did not differ from that of healthy controls. Consequently, catalytically inactive, cross-reactive immunological material (CRIM) was present, and the patient was CRIM-positive. This enzyme activity and immunoreactive enzyme concentration differs from those for previously known HEP patients, and represents a new mutation, evidence for heterogeneity in inherited uroporphyrinogen decarboxylase deficiency. PMID- 2322501 TI - Incidence of non-melanoma skin cancer in West Glamorgan, South Wales. AB - A population-based epidemiological study of non-melanoma skin cancer incidence was carried out over 6 months in an area of South Wales. A much higher incidence than expected of nonmelanoma skin cancer was found with crude annual rates per 100,000 population of 137.7 for basal cell carcinomas and 35.8 for squamous cell carcinomas, giving a combined rate of 173.5. When age was adjusted to the standardized world population the corresponding rates were 83.1, 19.0 and 102.1. Males were affected more than females and the ratio of basal cell carcinomas to squamous cell carcinomas was 4:1. These figures are at least 60% higher than previous estimates of the incidence of non-melanoma skin cancer in the U.K. There may be a higher incidence in this area because of the indigenous Celtic population, but there is almost certainly a substantial under-recording of non melanoma skin cancers throughout the U.K. PMID- 2322502 TI - Plasma exchange in refractory cutaneous vasculitis. AB - Eight patients with intractable cutaneous leucocytoclastic vasculitis were given a trial of plasma-exchange therapy. All but one improved, five substantially. Four have been successfully treated by intermittent plasma exchange for periods of 5-12 years. Apart from one episode of hepatitis B, possibly related to administration of fresh frozen plasma, no major adverse effects have occurred. Plasma exchange can be a valuable therapeutic option in patients with severe refractory cutaneous vasculitis. PMID- 2322503 TI - Erythropoietic protoporphyria and iron therapy. PMID- 2322504 TI - Cyclosporin A in psoriasis: interaction with carbamazepine. PMID- 2322506 TI - Albinism and anatomy. PMID- 2322505 TI - A controlled-trial of house dust mite eradication using natamycin in homes of patients with atopic dermatitis. PMID- 2322507 TI - Cataract surgery. PMID- 2322508 TI - Contamination of contact lens storage cases by Acanthamoeba and bacteria. AB - In order to identify possible risk factors for microbial keratitis the storage cases for contact lenses of 102 asymptomatic lens wearers were tested for contamination by bacteria and free-living amoebae. Of this group 43 had significant counts of viable bacteria and only 40 had negligible counts. Seven had contamination by acanthamoebae, of whom six also had significant bacterial counts. These results were categorised according to the type of contact lens worn and the lens disinfection method. The high rates of contamination by apathogenic and pathogenic organisms, in particular Acanthamoeba, and the probable support by contaminating bacteria of Acanthamoeba, are discussed. PMID- 2322509 TI - Albinism in childhood: a flash VEP and ERG study. AB - Flash visual evoked potentials (F. VEPs) and electroretinograms (ERGs) were recorded in a total of 20 young children with albinism (age range 5 months to 11 years, mean 4 years). All recordings were made without sedation. There were 13 oculocutaneous cases (one with Hermansky-Pudlak syndrome) and seven ocular albinos. Monocular flash stimulation commonly elicited an asymmetrical occipital VEP distribution with a well lateralised component at around 80 ms which was of opposite polarity in a comparison of VEPs from each eye. None of the normally pigmented matched controls or obligate female carriers showed this anomalous distribution. The albino electroretinogram, compared with controls, recorded under fully darkened conditions had a significantly larger a wave and significantly shorter latencies for both a and b waves. The accentuated ERG and asymmetrical VEP recorded in infants and young children with albinism permits distinction of these patients from those with congenital cone dysfunction and idiopathic nystagmus, with whom they may be confused by a clinical examination only. PMID- 2322510 TI - Visual outcome and complications after cataract extraction in Saudi Arabia. AB - Cataract is the leading cause of blindness in Saudi Arabia. The author studied 1383 patients who had undergone cataract extraction (total of 1520 procedures) from October 1985 to March 1986 at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. All patients were observed for at least two months. Of 1520 eyes 555 (37%) achieved a visual acuity of 20/40 or better, 309 (20%) a visual acuity of 20/50-20/60 after surgery, and 656 (43%) eyes a visual acuity of 20/70 or less. The number of eyes that had intraoperative complications was 176 (12%). The number of eyes that had postoperative complications was 539 (35%). Some eyes had more than one complication. The main factors responsible for failure to achieve visual acuity of 20/40 or better were: (1) error of refraction in 492 (32%) eyes; (2) pre-existing corneal scarring and opacity in 211 (14%) eyes; (3) climatic droplet keratopathy in 134 (9%); and (4) presumed visual loss due to glaucoma in 134 (9%) eyes. PMID- 2322511 TI - Immunohistological characterisation of retinoblastoma and related ocular tissue. AB - The immunohistological reactivity of six retinoblastomas was investigated by means of 18 monoclonal antibodies and compared with that of adult and fetal retina. The antigenic profiles were found to be characteristic for each cell type studied and indicated that a panel of monoclonal antibodies could achieve a specific immunolocalisation not afforded by any single antibody. Immunohistological comparison between retinoblastoma and adult and fetal retinal cells provided evidence of the histogenesis of the tumour. The data suggest that the tumour arises from an early multipotential cell, which retains the capacity to develop differentiation characteristics associated with inner or outer retinal cell types, resulting in a heterogeneous tumour cell population. A cell with such differentiation potential predominates in the retina prior to the primitive neuroepithelial layer division at eight weeks' gestation. PMID- 2322512 TI - Contact lenses for infant aphakia. AB - We prospectively studied for three years the optical correction by contact lenses of 83 aphakic infants (141 eyes) who generally also had systemic and other ocular anomalies: 85% of the patients tolerated the lens wear for the whole study period. Complications occurred in 46 eyes and led to cessation of lens wear in two cases. Ten patients abandoned the lenses for other reasons. Thirty-four eyes needed subsequent intraocular surgery, mostly minor, and nine patients had strabismus surgery. Contact lenses are a versatile, safe, successful, and cost effective treatment for aphakia in infancy against which, before their widespread introduction for primary optical correction of infant aphakia, other methods of aphakic treatment need to be compared. PMID- 2322513 TI - Binocularity following surgery for secondary esotropia in childhood. AB - Binocularity was assessed in children who developed large, constant esotropia following bilateral lateral rectus recessions for intermittent exotropia. Nine such patients were identified who warranted medical rectus recession. Seven were finally aligned within 6 prism dioptres after secondary surgery. Stereopsis measured 50 seconds or better in six of these patients and 200 seconds of arc in the seventh. Two patients had residual deviations: one child with 30 prism dioptres of residual esotropia had 400 arc seconds and the remaining patient, with 12 prism dioptres of exotropia and marked anisometropia, did not show stereopsis. Children with constant acquired esotropia for as long as two years may still have normal stereopsis after surgical alignment. The risk of losing binocularity because of a large overcorrection following exotropia surgery may be smaller than previously assumed. PMID- 2322514 TI - Immunoglobulins in paired specimens of vitreous and subretinal fluids from patients with rhegmatogenous retinal detachment. AB - Evidence suggests that there is a net movement of fluid through the retinal break in eyes with rhegmatogenous retinal detachment, this net movement being directed from the vitreous humour into the subretinal space. However, it remains uncertain how much fluid exchange occurs in both directions across such breaks. The concentration ratios of IgG/IgM or IgA/IgM, derived from assay of immunoglobulins in vitreous humour, subretinal fluid, and serum from a group of 19 such patients, suggest a lack of free, two-directional, fluid movement across the retinal break. Furthermore the IgG/IgM ratios for the two intraocular fluids were significantly greater than that of serum, this suggesting that these intraocular fluids are formed, at least in part, by a selective transduction of serum. PMID- 2322515 TI - Corneal oxygenation: blink frequency as a variable in rigid contact lens wear. AB - Using a micropolarographic system, we measured the responses of six human corneas to nine oxygen exposure conditions: to air (continuous open-eye) with no contact lens in place, and to eight interblink intervals (1, 2, 3, 4, 5, 6, 7, and 300 s durations) with an oxygen impermeable lens in place. The corneal oxygen uptake rates immediately following each of those conditions were direct indices of tear bulk-flow exchange under a rigid contact lens as an oxygen route. Greatest efficiencies in reducing corneal oxygen demand were associated with the two highest blink frequencies examined (namely, for interblink intervals of 2 s or less). Even at those frequencies oxygen demands ranging from 4 to 6 times the open-eye, non-wearing, baseline rate for each eye typically occurred, clearly justifying the need for a supplementary oxygenation route, for example, directly through rigid contact lens materials having inherently high oxygen permeabilities. PMID- 2322516 TI - Risk factors for proliferative sickle retinopathy. AB - The prevalence, incidence, and risk factors associated with proliferative sickle retinopathy (PSR) were investigated in 786 patients with homozygous sickle cell (SS) disease and 533 patients with sickle cell haemoglobin C (SC) disease. PSR was more common in SC disease, in which there was a significant predominance of males, and it increased with age in both genotypes. In SC disease the risk of developing PSR was highest between 15 and 24 years in males, between 20 and 39 years in females, and in SS disease between 25 and 39 years in both sexes. PSR tended to be bilateral, especially in SC disease. There was no evidence of familial clustering of PSR in SC siblings, and insufficient numbers of SS siblings were available to test for clustering. Haematological risk factors associated with PSR in SS disease were a high haemoglobin in males and a low fetal haemoglobin in both sexes and in SC disease, a high mean cell volume, and a low fetal haemoglobin in females. PMID- 2322517 TI - Retinal laser lenses: magnification, spot size, and field of view. AB - Proper use of ophthalmoscopic contact lenses for retinal photocoagulation requires knowledge of their comparative magnification, spot size, and field of view. We determined these parameters for four commonly used lenses, using data measured from optical components of the lenses and a commonly used photo coagulator slit-lamp and spot size changer. A Krieger lens has 8% more working field of view and 29% less magnification than a Goldmann lens. A Panfundoscope lens has 84% more working field of view and 24% less magnification than a Goldmann lens. A Mainster lens has 58% more working field of view and 3% more magnification than a Goldmann lens. For Goldmann, Krieger, Panfundoscope, and Mainster lenses, respectively, retinal spot size is 8%, 53%, 41%, and 5% greater than photo-coagulator spot size settings. The field of view of each lens is increased in myopic and decreased in hyperopic patients. Anterior segment irradiance is higher than retinal irradiance for 1000 microns spot size settings with a Panfundoscope or Mainster lens, and this setting should be avoided, especially in patients with hazy ocular media. PMID- 2322518 TI - Bilaterality of drusen. AB - The characteristics of drusen in 81 patients with bilateral drusen as a manifestation of age related disease were analysed for symmetry between the two eyes. It was found that there was close concordance with respect to drusen size, number, density, and fluorescence which was greater than would have been expected by chance alone. This finding implies that drusen may result from metabolic malfunction specific to the patient rather than the non-specific result of aging. PMID- 2322520 TI - Use of viscoelastic agents to aid visualisation during ocular surgery. PMID- 2322519 TI - Ptosis as the early manifestation of pituitary tumour. AB - Three patients who developed unilateral ptosis followed by partial third nerve palsy were found to have a pituitary tumour. The visual field defects were minimal and asymptomatic. Two patients had a chromophobe adenoma and one patient had a prolactinoma. The importance of recognising a pituitary tumour as the cause of acquired unilateral ptosis is emphasised. PMID- 2322521 TI - Tooth pulp changes following Le Fort I maxillary osteotomy in a primate model. AB - Le Fort I maxillary 'down-fracture' osteotomy with 8 mm advancement was performed in 15 adult rhesus monkeys. Forty-five tooth pulps were examined histologically at intervals from 0 to 24 weeks after surgery. Cell degeneration occurred in 31% of pulps examined, necrosis in 16% of pulps and osteo-dentine was found in 7% of pulps. Almost half of the teeth examined (47%) showed marked cellular changes, more frequently found in posterior teeth. Other features noted were inflammation (13%) and reactive dentine in pulps (24%). Axons degenerated initially but recovered by 24 weeks. It is concluded that Le Fort I maxillary osteotomy caused pulpal disturbances in an animal model and the extent to which this occurs in patients needs to be carefully monitored. PMID- 2322522 TI - Maxillofacial surgery: the economic aspect. AB - Fifteen years ago when the expenditure on the National Health Service was 2600 million pounds annually, an economic survey of the then more common procedures carried out by oral and maxillofacial surgeons in the UK was undertaken. After three reorganisations of the NHS with a fourth pending the overall cost has escalated to 21.6 billion pounds. The specialty has also seen significant change with a broader spectrum of work being carried out and a greater proportion of major cases being undertaken. The paper shows how previously costed procedures have changed; for example with increasing use of day care facilities and internal fixation techniques, before moving on to consider costings for the more advanced operations now being carried out on a regular basis. In an era of resource management with progressive stringency of funding in the acute sector it has been suggested that some procedures are uneconomical and others possibly should not take high priority. Under these circumstances it has become especially important to justify all facets of practice of the specialty and this aspect is considered in terms of the cost to the National Health Service, the quality of life of the patient and the cost to the economy as a whole in Social Security benefits and loss of productivity. PMID- 2322523 TI - The radiological prediction of inferior alveolar nerve injury during third molar surgery. AB - The surgical removal of an impacted mandibular third molar may result in damage to the inferior alveolar nerve and may cause disabling anaesthesia of the lip; anaesthesia of the lower gingivae and anterior teeth may also result. Assessing the likelihood of injury depends to a great extent on preoperative radiographic examination. Seven radiological diagnostic signs have been mentioned in the literature; the reliability of these signs as predictors of likely nerve injury have been evaluated through retrospective and prospective surveys. Three signs were found to be significantly related to nerve injury and a further two were probably important clinically. PMID- 2322524 TI - Pyknodysostosis: case report with surgical correction of the facial deformity. AB - Pyknodysostosis is a rare form of osteopetrosis. A case is reported together with a description of the surgical correction of the facial deformity and a discussion with regard to the complications. PMID- 2322525 TI - Keratocyst recurrences at intervals of more than 10 years: case reports. AB - The two cases reported here are of keratocysts which recurred after exceptionally long intervals. In the first case, the keratocyst recurred twice during the 37 year follow-up: 16 years after the initial operation and 21 years after the second. In the second case the recurrence occurred 14 years after surgical treatment. Recommendations for the duration of follow-up are discussed. PMID- 2322526 TI - Submandibular sialoadenitis due to a foreign body. AB - A case of a painful swelling of a submandibular gland in a 62-year-old woman is reported. This eventually proved to be caused by a foreign body (fish bone) in the main intrasalivary duct of the gland. PMID- 2322527 TI - The Marcus Gunn (jaw-winking) phenomenon: a case report. AB - The clinical features of the Marcus Gunn (jaw-winking) phenomenon are described and a case is reported in a 23-year-old female who also had congenital left duplex kidneys and ureters. PMID- 2322528 TI - An aid to the localisation of the mobilised premaxillary segment. AB - A device is described to aid localisation of the mobilised premaxillary segment during intermediate bone grafting of bilateral alveolar clefts. PMID- 2322529 TI - A manoeuvre to achieve intermaxillary fixation in fractures of the mandibular condyle with an open bite deformity. AB - A simple and easy manoeuvre is described to achieve intermaxillary fixation in those difficult cases of mandibular condylar neck fracture complicated by an anterior open bite. PMID- 2322530 TI - Selection and funding of trainees. PMID- 2322531 TI - Small plate osteosynthesis. PMID- 2322532 TI - An investigation into the effect of traumatically produced cerebrospinal fluid fistulae on the passage of Augmentin across the blood-brain barrier. AB - In the management of cerebrospinal fluid (csf) fistulae, associated with head and facial injury, prophylactic antimicrobial drugs are employed commonly to prevent the occurrence of bacterial meningitis. Under normal circumstances, penicillins achieve a low csf/plasma concentration ratio, but trauma may reduce the efficacy of the blood-brain barrier and permit increased amounts of penicillins to enter the csf. To test this hypothesis, with respect to Augmentin (amoxycillin and clavulanic acid), an animal study was undertaken. Under general anaesthesia, the brains and meninges of a group of 10 rabbits were traumatised to produce csf fistulae. Following the administration of an intravenous bolus of Augmentin, the blood and csf concentrations of Augmentin were measured over a period of 6 h and compared with those measurements from an untraumatised control group of 10 rabbits. No difference in the csf/plasma ratio was apparent between the two groups. The results of this study, therefore, suggest that trauma to the brain and meninges does not increase the permeability of the blood-brain barrier to Augmentin. PMID- 2322533 TI - Two-dimensional NMR studies of staphylococcal nuclease. 2. Sequence-specific assignments of carbon-13 and nitrogen-15 signals from the nuclease H124L thymidine 3',5'-bisphosphate-Ca2+ ternary complex. AB - Samples of staphylococcal nuclease H124L (cloned protein overproduced in Escherichia coli whose sequence is identical with that of the nuclease isolated from the V8 strain of Staphylococcus aureus) were labeled uniformly with carbon 13 (26% ul 13C), uniformly with nitrogen-15 (95% ul 15N), and specifically by incorporating nitrogen-15-labeled leucine ([98% 15N]Leu) or carbon-13-labeled lysine ([26% ul 13C]Lys), arginine ([26% ul 13C]Arg), or methionine ([26% ul 13C]Met). Solutions of the ternary complexes of these analogues (nuclease H124L pdTp-Ca2+) at pH 5.1 (H2O) or pH* 5.5 (2H2O) at 45 degrees C were analyzed as appropriate to the labeling pattern by multinuclear two-dimensional (2D) NMR experiments at spectrometer fields of 14.09 and 11.74 T: 1H-13C single-bond correlation (1H[13C]SBC); 1H-13C single-bond correlation with NOE relay (1H[13C]SBC-NOE); 1H-13C single-bond correlation with Hartmann-Hahn relay (1H [13C]SBC-HH); 1H-13C multiple-bond correlation (1H[13C]MBC); 1H-15N single-bond correlation (1H-[15N]SBC); 1H-15N single-bond correlation with NOE relay (1H[15N]SBC-NOE). The results have assisted in spin system assignments and in identification of secondary structural elements. Nuclear Overhauser enhancements (NOE's) characteristic of antiparallel beta-sheet (d alpha alpha NOE's) were observed in the 1H [13C]-SBC-NOE spectrum of the nuclease ternary complex labeled uniformly with 13C. NOE's characteristic of alpha-helix (dNN NOE's) were observed in the 1H[15N]SBC-NOE spectrum of the complex prepared from protein labeled uniformly with 15N. The assignments obtained from these multinuclear NMR studies have confirmed and extended assignments based on 1H[1H] 2D NMR experiments [Wang, J., LeMaster, D. M., & Markley, J. L. (1990) Biochemistry (preceding paper in this issue)]. PMID- 2322534 TI - The flavin-containing monooxygenase expressed in pig liver: primary sequence, distribution, and evidence for a single gene. AB - The primary sequence of the flavin-containing monooxygenase expressed in pig liver has been derived from the nucleotide sequence of cloned cDNA. The derived sequence is composed of 532 amino acids and represents a protein having a molecular weight of 58,952. The complete sequence was obtained from a single clone containing 2070 bases. A second clone, obtained from an independent library, yielded an identical sequence for the 1374 bases present. The amino acid composition compiled from the derived sequence is very similar to that obtained previously from the purified protein. In addition, a 10 amino acid sequence in a peptide formed from the purified protein by digestion with V8 protease exactly matches the derived sequence for residues 309-318. The flavin-containing monooxygenase expressed in pig liver is also expressed in pig lung and kidney as determined by analysis of both microsomal proteins and mRNA. The ratio of mRNA to protein for the enzyme in kidney is about 5 times greater than the same ratio for liver and about twice the ratio for lung. The reasons for these differences are not understood. Southern analysis of genomic DNA indicates that there is a single gene encoding the flavin-containing monooxygenase expressed in pig liver. Therefore, the broad activity of this enzyme in liver appears to be the result of the catalytic diversity of a single protein. PMID- 2322535 TI - Structure of the gene for human butyrylcholinesterase. Evidence for a single copy. AB - We have isolated five genomic clones for human butyrylcholinesterase (BChE), using cDNA probes encoding the catalytic subunit of the hydrophilic tetramer [McTiernan et al. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 6682-6686]. The BChE gene is at least 73 kb long and contains four exons. Exon 1 contains untranslated sequences and two potential translation initiation sites at codons -69 and -47. Exon 2 (1525 bp) contains 83% of the coding sequence for the mature protein, including the N-terminal and the active-site serine, and a third possible translation initiation site (likely functional), at codon -28. Exon 3 is 167 nucleotides long. Exon 4 (604 bp) codes for the C-terminus of the protein and the 3' untranslated region where two polyadenylation signals were identified. Intron 1 is 6.5 kb long, and the minimal sizes of introns 2 and 3 are estimated to be 32 kb each. Southern blot analysis of total human genomic DNA is in complete agreement with the gene structure established by restriction endonuclease mapping of the genomic clones: this strongly suggests that the BChE gene is present in a single copy. PMID- 2322536 TI - Halocyamines: novel antimicrobial tetrapeptide-like substances isolated from the hemocytes of the solitary ascidian Halocynthia roretzi. AB - Two novel antimicrobial tetrapeptide-like substances, halocyamine A and B, were isolated from the solitary ascidian Halocynthia roretzi by a procedure including extraction steps, chromatographies on coarse and fine HP-20 columns, and preparative reversed-phase high-performance liquid chromatography. The structures of halocyamine A and B were determined to be L-histidyl-L-6,7 dihydroxyphenylalanylglycyl-6-bromo-8,9-didehy drotryptamine and L-threonyl-L-6,7 dihydroxyphenylalanyl-L-histidyl-6-bromo-8,9- didehydrotryptamine, respectively, by spectral analyses and degradation studies. Besides antimicrobial activities against several kinds of bacteria and yeasts, both of them showed cytotoxic activities against neuronal cells cultured from rat fetal brain, mouse neuroblastoma N-18 cells, and human hepatoma Hep-G2 cells. They were only detected in the "morula"-like cells, which are of the most abundant cell type among the hemocytes of H. roretzi. PMID- 2322537 TI - Purification of PDGF-AB and PDGF-BB from human platelet extracts and identification of all three PDGF dimers in human platelets. AB - We have developed a panel of monoclonal antibodies to platelet-derived growth factor (PDGF) which have variable specificities for the three dimeric forms of the molecule (AA, AB, and BB). We have used these antibodies to detect and immunoaffinity purify the individual dimers from human platelet rich plasma. Extracts of outdated platelet preparations were initially chromatographed over CM Sepharose and then passed over the Sepharose-coupled monoclonal antibodies in series in selectively isolate the three dimeric forms of PDGF. The PDGF eluted from the affinity columns was subsequently further purified by reversed-phase HPLC. From 300 units of outdated platelet preparations, we purified 58 micrograms of PDGF-BB and 140 micrograms of PDGF-AB. Using the monoclonal antibodies to develop PDGF dimer-specific ELISAs, it was observed that all three PDGF dimer forms are present in fresh human platelet extracts and that the ratios of the three dimer forms vary depending upon the extraction conditions used. The identification of all three PDGF dimer forms in human platelets point to the need to view PDGF isolated from human platelets by conventional techniques as a mixture of all three forms and not solely as PDGF-AB. PMID- 2322538 TI - Prohormonal cleavage sites are associated with omega loops. AB - Secretory peptides are generated from larger precursor proteins, or prohormones, by proteolytic cleavage at sites consisting of one or more basic amino acids. We have investigated the association of these cleavage sites with the various classes of secondary structure in the prohormones. In particular, we determined the association of cleavage sites with the newly defined category of omega loops. We developed an algorithm for predicting the occurrence of such loops from the primary structure of the precursor and validated this procedure by comparison to crystallographic data. When this method was applied to prohormones, we found that about one-third of the cleavage sites previously assigned to reverse turns were actually associated with omega loops. Moreover, sites that delimit secreted peptides are most often associated with loops and are concentrated in the neck regions of the loops. These data are interpreted in terms of a model in which the processing endoprotease interacts with two sites on the prohormone: a recognition site in the middle of a loop and the cleavage site at its neck. PMID- 2322539 TI - Sequential resonance assignment and secondary structure determination of the Ascaris trypsin inhibitor, a member of a novel class of proteinase inhibitors. AB - The solution conformation of the Ascaris trypsin inhibitor, a member of a novel class of proteinase inhibitors, has been investigated by nuclear magnetic resonance spectroscopy. Complete sequence-specific assignments of the 1H NMR spectrum have been obtained by using a number of two-dimensional techniques for identifying through-bond and through-space (less than 5-A) connectivities. Elements of regular secondary structure have been identified on the basis of a qualitative interpretation of the nuclear Overhauser enhancement, coupling constant, and amide exchange data. These are two beta-sheet regions. One double stranded antiparallel beta-sheet comprises residues 11-14 (strand 1) and 37-39 (strand 2). The other triple-stranded sheet is formed by two antiparallel strands comprising residues 45-49 (strand 4) and 53-57 (strand 5) connected by a turn (residues 50-52), and a small strand consisting of residues 20-22 (strand 3) that is parallel to strand 4. PMID- 2322540 TI - 24-homologated 1,25-dihydroxyvitamin D3 compounds: separation of calcium and cell differentiation activities. AB - A series of 24-homologated 1,25-dihydroxyvitamin D3 compounds have been chemically synthesized and studied with regard to their activity in inducing differentiation of human promyelocyte HL-60 cells to monocytes and in calcium mobilizing activity in vitamin D deficient rats. Homologation of 1,25 dihydroxyvitamin D3 or its delta 22 analogue by one or two carbons increases by 10-fold and three-carbon homologation reduces by half the activity in causing differentiation of HL-60. On the other hand, homologation causes a substantial decrease in in vivo calcium mobilization activity. The addition of each carbon at the 24-position decreases binding to the HL-60 receptor or rat intestinal receptor by 5-10-fold so that binding affinity of the trihomo compound for the receptors is 130 times less that of 1,25-dihydroxyvitamin D3. Thus, binding affinity for the receptor cannot account for the preferential activity of the 24 homologated compounds in inducing cell differentiation. PMID- 2322541 TI - Tryptophan luminescence from liver alcohol dehydrogenase in its complexes with coenzyme. A comparative study of protein conformation in solution. AB - The extent of fluorescence quenching and that of phosphorescence quenching of Trp 15 and Trp-314 in alcohol dehydrogenase from horse liver as well as the intrinsic phosphorescence lifetime of Trp-314 in fluid solution have been utilized as structural probes of the macromolecule in binary and ternary complexes formed with coenzyme, analogous, and various substrate/inhibitors. Luminescence quenching by the coenzyme reveals that (1) while the reduced form quenches Trp emission exclusively from the fluorescent state, the oxidized form is very effective on the phosphorescent state as well and that (2) among the series of NADH binary and ternary complexes known by crystallographic studies to attain the closed form, distinct nicotinamide/indole geometrical arrangements are inferred from a variable degree of fluorescence quenching. Information of the dynamic structure of the coenzyme-binding domain derived from the phosphorescence lifetime of Trp-314 points out that within the series of closed NADH complexes there is considerable conformational heterogeneity. In solution, the variability in dynamical structure among the various protein complexes emphasizes that the closed/open forms identified by crystallographic studies are not two well-defined macrostates of the enzyme. PMID- 2322542 TI - Room temperature phosphorescence of Trp-314 as a monitor of subunit communications in alcohol dehydrogenase from horse liver. AB - The phosphorescence properties of liver alcohol dehydrogenase from horse were characterized at limiting concentrations of coenzyme and coenzyme analogues. The emission decay kinetics of Trp-314 in strong, slowly exchanging, ternary complexes with NADH/isobutyramide, NAD/pyrazole, and NADH/dimethyl sulfoxide displays a markedly nonexponential character. The analysis of decay components over the saturation curve reveals that the phosphorescence from singly bound protein molecules has a lifetime from 1 to 1.3 s, which is 2-3 times larger than observed with fully bound and unliganded enzyme. The remarkably tighter configuration reported by the triplet probe for the coenzyme-binding domain in half-saturated macromolecules is not exclusive of strongly inhibited ternary complexes. Measurements on binary complexes with NADH, ADPR, and the inactive coenzyme analogue 1,4,5,6-tetrahydronicotinamide adenine dinucleotide confirm that binding of the ligand to one subunit has qualitatively the same influence on protein structure. If the lifetime of Trp-314 provides clear evidence for an appreciable change in conformation at half-binding that is apparently triggered by the ADPR fragment of the coenzyme, such communication between subunits does not lead to allosteric phenomena in coenzyme binding. PMID- 2322543 TI - Angiogenin activates phospholipase C and elicits a rapid incorporation of fatty acid into cholesterol esters in vascular smooth muscle cells. AB - Angiogenin activates the phosphoinositide-specific phospholipase C (PLC) in cultured rat aortic smooth muscle cells to yield a transient (30 s) peak of 1,2 diacylglycerol (DG) and inositol trisphosphate. Within 1 min, the DG level falls below that of the control and remains so for at least 20 min. A transient increase in monoacylglycerol indicates that depletion of DG may be the consequence of hydrolysis by DG lipase. In addition to these changes in second messengers, a rapid increase in incorporation of radiolabeled tracer into cellular cholesterol esters is observed. Stimulated cholesterol ester labeling is inhibited by preincubation with either the DG lipase inhibitor RHC 80267 or the acyl coenzyme A:cholesterol acyltransferase inhibitor Sandoz 58035. Cells prelabeled with [3H]arachidonate show a sustained increase in labeling of cholesterol esters following exposure to angiogenin. In contrast, cells prelabeled with [3H]oleate show only a transient elevation that returns to the basal level by 5 min. This suggests initial cholesterol esterification by oleate followed by arachidonate that is released by stimulation of the PLC/DG lipase pathway. PMID- 2322544 TI - Protective effect of lipidic surfaces against pressure-induced conformational changes of poly(L-lysine). AB - Poly(L-lysine) bound to phosphatidylglycerol or phosphatidic acid bilayers was submitted to hydrostatic pressure in a diamond anvil cell to investigate whether the lipidic surfaces can protect the polypeptide against pressure-induced conformational transformations. The amide I region of the infrared spectrum of dimyristoylphosphatidic acid bound polylysine shows that most of the polypeptide retains its beta-sheet structure up to 19 kbar, while it is known to convert entirely to alpha-helix at approximately 2 kbar in the absence of the lipid [Carrier, D., Mantsch, H.H., & Wong, P.T.T. (1989) Biopolymers (in press)]. The simultaneous binding of the polypeptidic molecules to two opposing bilayers appears to be required in order to preserve the beta-sheet structure at pressures over approximately 9 kbar: a small proportion of the polypeptide, most likely the molecules at the surface of the aggregated bilayers, was found to convert to unordered and eventually to alpha-helical conformations in the pressure range 9 19 kbar. The decrease from 1612 to 1606 cm-1 of the frequency of the major beta sheet component of the infrared amide I band as the pressure is raised to 6 kbar indicates a strengthening of the interchain hydrogen bonds. The high-pressure infrared spectra of polylysine bound to dimyristoyl- and dipalmitoylphosphatidylglycerol show that the polypeptide remains alpha-helical up to approximately 12 kbar, though the changes in the bandshape indicate an increase in hydrogen bond strength. The formation of a small amount of beta-sheet was observed during decompression and is attributed to the effect of dehydration on the polypeptidic molecules located at the surface of the aggregates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322545 TI - Iron environment in ferritin with large amounts of phosphate, from Azotobacter vinelandii and horse spleen, analyzed using extended X-ray absorption fine structure (EXAFS). AB - The iron core of proteins in the ferritin family displays structural variations that include phosphate content as well as the number and the degree of ordering of the iron atoms. Earlier studies had shown that ferritin iron cores naturally high in phosphate, e.g., Azotobacter vinelandii (AV) ferritin (Fe:P ratio = 1:1.7), had decreased long-range order. Here, the influence of phosphate on the local structure around iron in ferritin cores is reported, comparing the EXAFS of AV ferritin, reconstituted ferritin [the protein coats of horse spleen ferritin mixed with Fe(II) with and without phosphate at pH 7] (Fe:P ratio = 1:0.25), and native horse spleen ferritin (Fe:P ratio = 1:0.125); reconstituted horse spleen ferritin without phosphate was indistinguishable from native horse spleen ferritin (HSF) in the analysis. In contrast, when the phosphate content was high in AV ferritin and horse spleen ferritin reconstituted with phosphate, the average iron atom had five to six phosphorus neighbors at 3.17 A. Moreover, the number of detectable iron neighbors was lower when phosphate was high or present during reconstitution (2-3 vs 5-6), and the interatomic distance was longer (3.50 vs 3.03 A), indicating that some phosphate bridges neighboring iron atoms. However, the decrease in the number of detectable iron-iron neighbors compared to HSF and the higher number of Fe-P interactions relative to Fe-Fe interactions suggest that some phosphate ligands were chain termini, or blocked crystal growth, and/or introduced defects which contributed both to the long-range disorder and to altered redox properties previously observed in AV ferritin. PMID- 2322546 TI - Thermodynamic and spectroscopic study of bulge loops in oligoribonucleotides. AB - Thermodynamic parameters for bulge loops of one to three nucleotides in oligoribonucleotide duplexes have been measured by optical melting. The results indicate bulges Bn of An and Un have similar stabilities in the duplexes, GCGBmGCG + CGCCGC. The stability increment for a bulge depends on more than its adjacent base pairs. For example, the stability increment for a bulge is affected more than 1 kcal/mol by changing two nonadjacent base pairs or by adding terminal unpaired nucleotides (dangling ends) three base pairs away. Thus a nearest neighbor approximation for helixes with bulges is oversimplified. Many of the non self-complementary strands used in this study were observed to form homoduplexes. Such duplexes with GA mismatches were particularly stable. PMID- 2322547 TI - Aminophospholipid translocation in erythrocytes: evidence for the involvement of a specific transporter and an endofacial protein. AB - The transport of exogenously supplied fluorescent analogues of aminophospholipids from the outer to inner leaflet in red blood cells (RBC) is dependent upon the oxidative status of membrane sulfhydryls. Oxidation of a sulfhydryl on a 32-kDa membrane protein by pyridyldithioethylamine (PDA) has been previously shown [Connor & Schroit (1988) Biochemistry 27, 848-851] to inhibit the transport of NBD-labeled phosphatidylserine (NBD-PS). In the present study, other sulfhydryl oxidants were examined to determine whether additional sites are involved in the transport process. Our results show that diamide inhibits the transport of NBD-PS via a mechanism that is independent of the 32-kDa site. This is shown by the inability of diamide to block labeling of the 32-kDa sulfhydryl with 125I-labeled PDA and to protect against PDA-mediated inhibition of NBD-PS transport. diamide mediated inhibition, but not PDA-mediated inhibition, could be reversed by reduction with cysteamine or endogenous glutathione. Similarly, treatment of RBC with 5,5'-dithiobis(2-nitrobenzoic acid), which depletes endogenous glutathione and induces oxidation of endofacial proteins [Reglinski et al. (1988) J. Biol. Chem. 263, 12360-12366], inhibited NBD-PS transport in a manner analogous to diamide. Once established, the asymmetric distribution of NBD-PS could not be altered by oxidation of either site. These data indicate that a second site critical to the transport of aminophospholipids resides on the endofacial surface and suggest that the transport of aminophospholipids across the bilayer membrane of RBC depends on a coordinated and complementary process between a cytoskeletal component and the 32-kDa membrane polypeptide; both must be operative for transport to proceed. PMID- 2322548 TI - UDP-GlcNAc transport across the Golgi membrane: electroneutral exchange for dianionic UMP. AB - We have examined the coupling and charge stoichiometry for UDP-GlcNAc transport into Golgi-enriched vesicles from rat liver. In the absence of added energy sources, these Golgi vesicles concentrate UDP-GlcNAc at least 20-fold, presumably by exchange with endogenous nucleotides. Under the conditions used, extravesicular degradation of UDP-GlcNAc has been eliminated, and less than 15% of the internalized radioactivity becomes associated with endogenous macromolecules. Of the remaining intravesicular label, 85% remains unmetabolized UDP-[3H]GlcNAc, and approximately 15% is hydrolyzed to [3H]GlcNAc-1-phosphate. Efflux of accumulated UDP-[3H]GlcNAc is induced by addition of UMP, UDP, or UDP galactose to the external medium. Permeabilization of Golgi vesicles causes a rapid and nearly complete loss of internal UDP-[3H]GlcNAc, indicating that the results reflect transport and not binding. Moreover, transport of UDP-[3H]GlcNAc into these Golgi vesicles was stimulated up to 5-fold by mechanically preloading vesicles with either UDP-GlcNAc or UMP. The response of UMP/UMP exchange and UMP/UDP-GlcNAc exchange to alterations in intravesicular and extravesicular pH suggests that UDP-GlcNAc enters the Golgi apparatus in electroneutral exchange with the dianionic form of UMP. PMID- 2322549 TI - Melittin binding to mixed phosphatidylglycerol/phosphatidylcholine membranes. AB - The binding of bee venom melittin to negatively charged unilamellar vesicles and planar lipid bilayers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) was studied with circular dichroism and deuterium NMR spectroscopy. The melittin binding isotherm was measured for small unilamellar vesicles containing 10 or 20 mol % POPG. Due to electrostatic attraction, binding of the positively charged melittin was much enhanced as compared to the binding to neutral lipid vesicles. However, after correction for electrostatic effects by means of the Gouy-Chapman theory, all melittin binding isotherms could be described by a partition Kp = (4.5 +/- 0.6) x 10(4) M-1. It was estimated that about 50% of the total melittin surface was embedded in a hydrophobic environment. The melittin partition constant for small unilamellar vesicles was by a factor of 20 larger than that of planar bilayers and attests to the tighter lipid packing in the nonsonicated bilayers. Deuterium NMR studies were performed with coarse lipid dispersions. Binding of melittin to POPC/POPG (80/20 mol/mol) membranes caused systematic changes in the conformation of the phosphocholine and phosphoglycerol head groups which were ascribed to the influence of electrostatic charge on the choline dipole. While the negative charge of phosphatidylglycerol moved the N+ end of the choline -P-N+ dipole toward the bilayer interior, the binding of melittin reversed this effect and rotated the N+ end toward the aqueous phase. No specific melittin-POPG complexes could be detected. The phosphoglycerol head group was less affected by melittin binding than its choline counterpart. PMID- 2322550 TI - Membrane curvature, lipid segregation, and structural transitions for phospholipids under dual-solvent stress. AB - Amphiphiles respond both to polar and to nonpolar solvents. In this paper X-ray diffraction and osmotic stress have been used to examine the phase behavior, the structural dimensions, and the work of deforming the monolayer-lined aqueous cavities formed by mixtures of dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC) as a function of the concentration of two solvents, water and tetradecane (td). In the absence of td, most PE/PC mixtures show only lamellar phases in excess water; all of these become single reverse hexagonal (HII) phases with addition of excess td. The spontaneous radius of curvature R0 of lipid monolayers, as expressed in these HII phases, is allowed by the relief of hydrocarbon chain stress by td; R0 increases with the ratio DOPC/DOPE. Mixtures with very large R0's can have water contents higher than the L alpha phases that form in the absence of td. The drive for hydration is understood in terms of the curvature energy to create large water cavities in addition to direct hydration of the polar groups. Much of the work of removing water to create hexagonal phases of radius R less than R0 goes into changing monolayer curvature rather than dehydrating polar groups. Single HII phases stressed by limited water or td show several responses. (a) The molecular area is compressed at the polar end of the molecule and expanded at the hydrocarbon ends. (b) For circularly symmetrical water cylinders, the degrees of hydrocarbon chain splaying and polar group compression are different for molecules aligned in different directions around the water cylinder. (c) A pivotal position exists along the length of the phospholipid molecule where little area change occurs as the monolayer is bent to increasing curvatures. (d) By defining R0 at the pivotal position, we find that measured energies are well fit by a quadratic bending energy, K0/2 (1/R-1/R0); the fit yields bilayer bending moduli of Kc = (1.2-1.7) X 10(-12) ergs, in good agreement with measurements from bilayer mechanics. (e) For lipid mixtures, enforced deviation of the HII monolayer from R0 is sufficiently powerful to cause demixing of the phospholipids in a way suggesting that the DOPE/DOPC ratio self-adjusts so that its R0 matches the amount of td or water available, i.e., that curvature energy is minimized. PMID- 2322551 TI - Activation of human factor V by factor Xa and thrombin. AB - The activation of human factor V by factor Xa and thrombin was studied by functional assessment of cofactor activity and sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by either autoradiography of 125I labeled factor V activation products or Western blot analyses of unlabeled factor V activation products. Cofactor activity was measured by the ability of the factor V/Va peptides to support the activation of prothrombin. The factor Xa catalyzed cleavage of factor V was observed to be time, phospholipid, and calcium ion dependent, yielding a cofactor with activity equal to that of thrombin activated factor V (factor Va). The cleavage pattern differed markedly from the one observed in the bovine system. The factor Xa activated factor V subunits expressing cofactor activity were isolated and found to consist of peptides of Mr 220,000 and 105,000. Although thrombin cleaved the Mr 220,000 peptide to yield peptides previously shown to be products of thrombin activation, cofactor activity did not increase. N-Terminal sequence analysis confirmed that both factor Xa and thrombin cleave factor V at the same bond to generate the Mr 220,000 peptide. The factor Xa dependent functional assessment of 125I-labeled factor V coupled with densitometric analyses of the cleavage products indicated that the cofactor activity of factor Xa activated factor V closely paralleled the appearance of the Mr 220,000 peptide. This observation facilitated the study of the kinetics of factor V activation by allowing the activation of factor V to be monitored by the appearance of the Mr 220,000 peptide (factor Xa activation) or the Mr 105,000 peptide (thrombin activation). Factor Xa catalyzed activation of factor V obeyed Michaelis-Menten kinetics and was characterized by a Km of 10.4 nM, a kcat of 2.6 min-1, and a catalytic efficiency (kcat/Km) of 4.14 X 10(6) M-1 s-1. The thrombin-catalyzed activation of factor V was characterized by a Km of 71.7 nM, a kcat of 14.0 min-1, and a catalytic efficiency of 3.26 X 10(6) M-1 s 1. This indicates that factor Xa is as efficient an enzyme toward factor V as thrombin. PMID- 2322552 TI - Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein lipase and hepatic lipase: implications for the mechanisms of lipase action. AB - To explore how enzyme affinities and enzyme activities regulate hydrolysis of water-insoluble substrates, we compared hydrolysis of phospholipid-stabilized emulsions of medium-chain (MCT) versus long-chain triacylglycerols (LCT). Because substrate solubility at the emulsion surface might modulate rates of hydrolysis, the ability of egg yolk phosphatidylcholine to solubilize MCT was examined by NMR spectroscopy. Chemical shift measurements showed that 11 mol % of [13C]carbonyl enriched trioctanoin was incorporated into phospholipid vesicles as a surface component. Similar methods with [13C]triolein showed a maximum solubility in phospholipid bilayers of 3 mol % (Hamilton & Small, 1981). Line widths of trioctanoin surface peaks were half that of LCT, and relaxation times, T1, were also shorter for trioctanoin, showing greater mobility for MCT in phospholipid. In assessing the effects of these differences in solubility on lipolysis, we found that both purified bovine milk lipoprotein lipase and human hepatic lipase hydrolyzed MCT at rates at least 2-fold higher than for LCT. With increasing concentrations of MCT, saturation was not reached, indicating low affinities of lipase for MCT emulsions, but with LCT emulsion incubated with lipoprotein lipase, saturation was reached at relatively low concentration, demonstrating higher affinity of lipase for LCT emulsions. Differences in affinity were also demonstrated in mixed incubations where increasing amounts of LCT emulsion resulted in decreased hydrolysis of MCT emulsions. Increasing MCT emulsion amounts had little or no effect on LCT emulsion hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322553 TI - Purification and characterization of corticosteroid side chain isomerase. AB - Corticosteroid side chain isomerase of rat liver catalyzes the interconversion of the ketol (20-oxo-21-ol) and aldol (20-hydroxy-21-al) forms of the corticosteroid side chain. The enzyme has now been purified to apparent homogeneity from rat liver cytosol by sequential chromatography on anionic, hydroxylapatite, and gel filtration columns. Ketol-aldol isomerization is followed by measuring the exchange of tritium from 21-tritiated steroids with water. The native enzyme is a dimer of MW 44,000. The isoelectric point is 4.8 +/- 0.1 pH units. The purified enzyme is stimulated by Co3+ or Ni2+. The enzyme utilizes 11-deoxycorticosterone, corticosterone, and 17-deoxycortisol as substrate but not cortisol, tetrahydrocortisol, and prednisolone. Tritium-water exchange of (21S)-[21-3H]DOC is a pseudo-first-order reaction; 21-3H exchange from the 21R isomer proceeds with first-order kinetics only after a lag associated with its epimerization to the 21S form. PMID- 2322554 TI - Isolation and characterization of a complementary DNA clone coding for the E1 beta subunit of the bovine branched-chain alpha-ketoacid dehydrogenase complex: complete amino acid sequence of the precursor protein and its proteolytic processing. AB - A 1.7-kb cDNA clone encoding the entire precursor of the E1 beta subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex was isolated from a bovine liver cDNA library by screening with a mixture of synthetic oligonucleotide probes corresponding to the C-terminal five-residue sequence of the mature E1 beta subunit. A partial amino acid sequence was determined by Edman degradation of the intact subunit and the peptides generated by cleavage at the lysyl bonds. Nucleotide sequence analysis revealed that the isolated cDNA clone contained the 5'-untranslated sequence of 186 nucleotides, the translated sequence of 1176 nucleotides, and the 3'-untranslated sequence of 306 nucleotides with a poly(A) tail. A type AATAAA polyadenylation signal was located 17 nucleotides upstream of the start of a poly(A) tail. Comparison of the amino acid sequence predicted from the nucleotide sequence of the cDNA insert of the clone with the partial amino acid sequence of the mature BCKDH E1 beta subunit showed that the cDNA insert encodes for a 342 amino acid subunit with Mr 37,745 and that the subunit is synthesized as the precursor with a leader sequence of 50 amino acids and processed at the N-terminus. Northern blot analysis using the cDNA insert as a probe showed the presence of a 1.8-1.9-kb mRNA in bovine liver, suggesting that the insert covers nearly a full length of mRNA. Alignment of the deduced amino acid sequence of bovine BCKDH E1 beta with that of the human pyruvate dehydrogenase (PDH) complex E1 beta subunit revealed a high degree of sequence homology throughout the two enzymes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322555 TI - Excimer fluorescence of pyrenyliodoacetamide-labeled tropomyosin: a probe of the state of tropomyosin in reconstituted muscle thin filaments. AB - Rabbit skeletal tropomyosin (Tm) specifically labeled at cysteine groups with N (1-pyrenyl)-iodoacetamide (PIA) exhibits excimer fluorescence. The excimer fluorescence was sensitive to the local conformation of Tm, to actin binding, and, in reconstituted thin filaments, to the Tm state change induced by binding of myosin subfragment 1 (S1). The properties of PIATm were similar to previously studied pyrenylmaleimide-labeled Tm (PMTm) [Ishii, Y., & Lehrer, S.S. (1985) Biochemistry 24, 6631] except that S1 binding to actin-Tm increased the excimer fluorescence in contrast to the time-dependent decrease seen for PMTm. The fluorescence properties of PIATm are sensitive to the Tm chain-chain interaction via equilibria among pyrene configurations and nonfluorescent dimer as well as the monomer and excimer-forming configurations. The effect of bound troponin (Tn) on the excimer fluorescence of PIATm in the reconstituted systems was dependent on ionic strength with a slight Ca2+ dependence. S1 titrations in the absence and presence of Tn and Ca2+ indicated that the excimer fluorescence probes the state change of Tm from the weak S1 binding state to the strong S1 binding state which is facilitated by Ca2+ [Hill et al. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 3186]. Binding of MgADP-S1 and MgAMPPNP-S1 produced the same total excimer fluorescence change as for nucleotide-free S1, showing that the strong S1 binding state of Tm-actin is independent of nucleotide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322556 TI - Molecular modeling of human complement component C4 and its fragments by X-ray and neutron solution scattering. AB - The solution structures of human complement component C4 and five derived fragments, C4u, C4(a + b), C4b, C4c, and C4d, were analyzed by synchrotron X-ray and neutron scattering. The X-ray radii of gyration RG for C4, C4u, and C4(a + b) in H2O buffers are similar at 5.23-5.28 nm, and likewise the cross-sectional radii of gyration RXS are similar at 2.48-2.52 nm. Molecular mass calculations using X-rays and neutrons show unexpectedly that C4c is dimeric; however, all the other forms are monomeric. C4c2 has an X-ray RG of 5.18 nm and an RXS of 2.89 nm. Neutron contrast variation gives RG values at infinite contrast of 4.87-4.93 nm for C4 and C4u, 4.79 nm for C4b, 4.94 nm for C4c2, and 2.69 nm for C4d. The RXS values at infinite contrast are 2.23-2.25 nm for C4 and C4u, 1.89 nm for C4b, and 2.62 nm for C4c2. These data show that a large conformational change occurs on going from C4 to C4b, but not on going from C4 to C4u, and this is attributed to the presence of the C4a moiety in C4u. Comparisons of the C4 and C4u scattering curves show that these are very similar out to a nominal resolution of 4 nm. Scattering-curve models were developed to account for the neutron scattering curves of C4, C4c2, and C4d in 2H2O buffers. The C4c monomer could be represented by a lamellar ellipsoid of size 8 nm x 2 nm x 18 nm. C4d was found to be 4 nm x 2 nm x 9 nm. The combination of these structures gave good accounts of the neutron data for C4, C4b, and C4c2 to resolutions of 5-6 nm. The C4 model was obtained by placing the long axis of C4d parallel to that of C4c such that the cross section is extended. C4b was best modeled by repositioning C4d relative to C4c such that this cross section becomes more compact. The C4 and C4b models are compared with possible structures for the C1 component of complement to show the importance of the surface accessibility of the protease domains and short consensus repeat domains in C1 for C4 activation. PMID- 2322557 TI - Photoaffinity labeling of the Torpedo californica nicotinic acetylcholine receptor with an aryl azide derivative of phosphatidylserine. AB - A photoactivatable analogue of phosphatidylserine, 125I-labeled 4-azidosalicylic acid-phosphatidylserine (125I ASA-PS), was used to label both native acetylcholine receptor (AchR)-rich membranes from Torpedo californica and AchR membranes affinity purified from Torpedo reconstituted into asolectin (a crude soybean lipid extract) vesicles. The radioiodinated arylazido group attaches directly to the phospholipid head group and thus probes for regions of the AchR structure in contact with the negatively charged head group of phosphatidylserine. All four subunits of the AchR incorporated the label, with the alpha subunit incorporating approximately twice as much as each of the other subunits on a per mole basis. The regions of the AchR alpha subunit that incorporated 125I ASA-PS were mapped by Staphylococcus aureus V8 protease digestion. The majority of label incorporated into fragments representing a more complete digestion of the alpha subunit was localized to 11.7- and 10.1-kDa V8 cleavage fragments, both beginning at Asn-339 and of sufficient length to contain the hydrophobic regions M1, M2, and M3 was also significantly labeled. In contrast, V8 cleavage fragments representing roughly a third of the amino terminal portion of the alpha subunit incorporated little or no detectable amount of probe. PMID- 2322558 TI - Organization of the gene for platelet glycoprotein IIb. AB - The glycoprotein (GP) IIb/IIIa heterodimer functions as a receptor for fibrinogen, von Willebrand factor, and fibronectin on activated platelets; it is dysfunctional in the bleeding diathesis Glanzmann's thrombasthenia. This receptor is a member of the integrin family, which includes homologous membrane receptors involved in a number of different cell-cell and cell-matrix adhesive interactions. Knowledge of the sequence and organization of the GPIIb and GPIIIa genes will help in understanding evolutionary relationships and functional homologies of this family of adhesion protein receptors and will facilitate analysis of molecular defects responsible for thrombasthenia. Using the GPIIb cDNA as a probe, we have isolated overlapping genomic clones encompassing the entire coding region, the 5'- and 3'-untranslated sequences, and the immediate flanking regions for the GPIIb gene. The gene spans approximately 17.2 kilobases (kb); all but approximately 2.6 kb of intronic DNA sequence has been determined. The GPIIb gene contains 30 exons whose demarcations do not correlate with previously suggested functional domains. Two intron/exon borders have the rare GC splice donor sequence instead of the consensus GT sequence. There are at least seven complete and three partial AluI sequence repeats within the intron sequences. RNase protection, S1 nuclease analysis, and primer extension studies using human erythroleukemia (HEL) cell RNA and platelet RNA map a major transcription start site 32 base pairs (bp) 5' to the beginning of the coding region; however, there are no canonical consensus TATA or CAAT boxes in the region immediately 5' to the proposed cap site. The immediate 5'-flanking sequence of rodent GPIIb demonstrates complete identity near the proposed cap site with its human counterpart, but again, no TATA or CAAT boxes are apparent. PMID- 2322559 TI - Structural and functional features of the alpha 3 chain indicate a bridging role for chicken collagen VI in connective tissues. AB - Type VI collagen is a component of 100 nm long periodic filaments with a widespread distribution around collagen fibers and on the surface of cells. It is an unusual collagen constituted by three distinct chains, one of which (alpha 3) is much larger than the others and is encoded by a 9-kb mRNA. The amino acid sequence of the alpha 3(VI) deduced from the present cDNA clones specifies for a multidomain protein of at least 2648 residues made of a short collagenous sequence (336 residues), flanked at the N-terminus by nine 200 residue long repeating motifs and at the C-terminus by two similar motifs that share extensive identities with the collagen-binding type A repeats of von Willebrand factor. Type VI collagen and alpha 3(VI) fusion proteins bound to insolubilized type I collagen in a specific, time-dependent, and saturable manner. The alpha 3(VI) chain has three Arg-Gly-Asp sequences in the collagenous domain, and cell attachment was stimulated by the triple helix of type VI collagen and by alpha 3(VI) fusion proteins containing Arg-Gly-Asp sequences. This function was specifically inhibited by the Arg-Gly-Asp-Ser synthetic peptide. The type I collagen-binding and the cell-attachment properties of the alpha 3(VI) chain provide direct information for the role of type VI collagen in connective tissues. PMID- 2322560 TI - pH-induced conformational states of bovine growth hormone. AB - The folding behavior of bovine growth hormone (bGH) is examined by chemical and pH denaturation using several spectroscopic probes of protein secondary and tertiary structure. Partially denaturing concentrations of urea eliminate the native-state quenching of intrinsic tryptophan fluorescence, from the single protein tryptophan, but the fluorescence emission spectrum is not red-shifted like the unfolded state, and the protein retains substantial secondary structure. A neutral-to-acid pH shift also eliminates tryptophan quenching; however, the loss of quenching is not accompanied by an emission red-shift. In addition, the protein undergoes a pH-dependent UV absorbance transition; the changes in absorptivity have the same midpoint as the transition associated with the change in intrinsic tryptophan fluorescence. The magnitude of the absorption transition is similar to that observed previously for urea denaturation of the protein. In a similar fashion, a pH-dependent CD transition is also observed; however, the transition occurs at a higher pH. The behavior of the various optical probes indicates that the pH-induced conformational transition produces a highly populated species in which the microenvironment surrounding the single protein tryptophan residue resembles that observed during the urea-induced unfolding/refolding transition. The pH-induced changes in tertiary structure occur at a lower pH than the changes associated with a portion of the secondary structure. Proton NMR of the low-pH intermediate indicates that the three His and six Tyr resonances are indistinguishable from the unfolded state. The intermediate(s) observed by either chemical or pH-induced denaturation resemble(s) a molten globule state which contains significant secondary structure. The residual secondary structure present in the intermediate could be nonnative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322561 TI - Charge effects on folded and unfolded proteins. AB - We develop a theory for the effects of charge on the stabilization of globular proteins. The folding process is modeled as occurring through a fictitious intermediate state along a two-part thermodynamic pathway in which the molecule (i) increases its density and then (ii) rearranges its ionic groups to the protein surface. The equilibrium for the binding of protons in salt solutions is assumed to be driven by the electrical potential due to the charge distribution, in addition to the intrinsic binding affinity and bulk proton concentration. The potential is calculated for inside and outside a porous sphere model of the protein using the Poisson-Boltzmann relation, wherein the interior dielectric constant is taken to be a linear function of the chain density. The model predicts the slope of the titration curves for native myoglobin in agreement with experiments by Breslow and Gurd (1962). From the similar experiments on the unfolded state, and from the experiments of Privalov et al. (1986) on the intrinsic viscosity of the unfolded molecules, the theory shows that the unfolded state has a much higher density than a chain in a theta solvent and that the density increases with ionic strength. In addition, from the free energy of proton binding to the protein, we also calculate the electrostatic contributions to protein stability, a major contribution deriving from changes in ionization. We consider the example of the stability of myoglobin as a function of pH, ionic strength, and ionic groups buried in the native protein structure. We show that although maximum stability of most proteins should occur at their isoelectric point, the burial of nontitratable groups should lead to maximum stabilities at pH values other than the isoelectric point. PMID- 2322562 TI - Structural studies of cytochrome b5: complete sequence-specific resonance assignments for the trypsin-solubilized microsomal ferrocytochrome b5 obtained from pig and calf. AB - We report complete sequence-specific proton resonance assignments for the trypsin solubilized microsomal ferrocytochrome b5 obtained from calf liver. In addition, sequence-specific resonance assignments for the main-chain amino acid protons (i.e., C alpha, C beta, and amide protons) are also reported for the porcine cytochrome b5. Assignment of the majority of the main-chain resonances was rapidly accomplished by automated procedures that used COSY and HOHAHA peak coordinates as input. Long side chain amino acid spin system identification was facilitated by long-range coherence-transfer experiments (HOHAHA). Problems with resonance overlap were resolved by examining differences between the two dimensional 500-MHz NMR spectra of rabbit, pig, and calf proteins and by examining the temperature-dependent variation of amide proton resonances. Calculations of the aromatic ring-current shifts for protons that the X-ray crystal structure indicated were proximal to aromatic residues were found to be useful in corroborating assignments, especially those due to the large shifts induced by the heme. Assignment of NOESY cross peaks was greatly facilitated by a prediction of intensities using a complete relaxation matrix analysis based on the crystal structure. These results suggest that the single-crystal X-ray structure closely resembles that of the solution structure although there is evidence that the solution structure has a more dynamic character. PMID- 2322563 TI - 13C and 15N nuclear magnetic resonance evidence of the ionization state of substrates bound to bovine dihydrofolate reductase. AB - The state of protonation of substrates bound to mammalian dihydrofolate reductase (DHFR) has significance for the mechanism of catalysis. To investigate this, dihydrofolate and dihydropteroyl-pentaglutamate have been synthesized with 15N enrichment at N-2. 15N NMR studies have been performed on the binary complexes formed by bovine DHFR with these compounds and with [5-15N]dihydrobiopterin. The results indicate that there is no protonation at N-5 in the binary complexes, and this was confirmed by 13C NMR studies with folate and dihydrofolate synthesized with 13C enrichment at C-6. The chemical shift displacements produced by complex formation are in the same direction as those which result from deprotonation of the N-3/C-4-O "amide" group and are consistent with at least partial loss of the proton from N-3. This would be possible if, as crystallographic data indicate, there is interaction of N-3 and the 2-amino group of the bound ligands with the carboxylate of the active site glutamate residue (Glu30). PMID- 2322564 TI - Exchange and flip-flop of dimyristoylphosphatidylcholine in liquid-crystalline, gel, and two-component, two-phase large unilamellar vesicles. AB - The rate and extent of spontaneous exchange of dimyristoylphosphatidylcholine (DMPC) from large unilamellar vesicles (LUV) composed of either DMPC or mixtures of DMPC/distearoylphosphatidylcholine (DSPC) have been examined under equilibrium conditions. The phase state of the vesicles ranged from all-liquid-crystalline through mixed gel/liquid-crystalline to all-gel. The exchange rate of DMPC between liquid-crystalline DMPC LUV, measured between 25 and 55 degrees C, was found to have an Arrhenius activation energy of 24.9 +/- 1.4 kcal/mol. This activation energy and the exchange rates are very similar to those obtained for the exchange of DMPC between DMPC small unilamellar vesicles (SUV). The extent of exchange of DMPC in LUV was found to be approximately 90%. This is in direct contrast to the situation in DMPC SUV where only the lipid in the outer monolayer is available for exchange. Thus, transbilayer movement (flip-flop) is substantially faster in liquid-crystalline DMPC LUV than in SUV. Desorption from gel-phase LUV has a much lower rate than gel-phase SUV with an activation energy of 31.7 +/- 3.7 kcal/mol compared to 11.5 +/- 2 kcal/mol reported for SUV. A defect-mediated exchange in gel-phase SUV, which is not the major pathway for exchange in LUV, is proposed on the basis of the thermodynamic parameters of the activation process. Surprisingly, the rates of DMPC exchange between DMPC/DSPC two-component LUV, measured over a wide range of compositions and temperatures, were found to exhibit very little dependence on the composition or phase configuration of the vesicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322565 TI - Deformation and instability in membrane structure of phospholipid vesicles caused by osmophobic association: mechanical stress model for the mechanism of poly(ethylene glycol)-induced membrane fusion. AB - The mechanism of poly(ethylene glycol)-induced fusion of phospholipid vesicles was studied based on the "osmophobic association" theory which was recently proposed both theoretically [Ito, T., Yamazaki, M., & Ohnishi, S. (1989) Biochemistry 28, 5626-5630] and also experimentally [Yamazaki, M., Ohnishi, S., & Ito, T. (1989) Biochemistry 28, 3710-3715]. Osmophobic association and fusion were detected by measuring the light scattering of the vesicle suspension; the former was detected from the increase in light scattering induced by the addition of PEG, and the latter was from the irreversibility of the increase in light scattering. Threshold concentrations of PEG were required not only for osmophobic association but also for fusion. The threshold concentration for fusion depended on the molecular weight of PEG and also on the electrostatic repulsive interaction between phospholipid vesicles, which was manipulated by the use of vesicles with negative surface charge; increasing the molecular weight of PEG lowered the threshold concentration, and increasing the electrostatic repulsive interaction raised it. In addition, a transient leakage of internal contents from the vesicles was observed at the concentration that caused fusion. When the surface charge of the vesicle was varied, the threshold for fusion coincided with that for osmophobic association, provided that the latter exceeded 22 wt % of PEG 6000. However, when the threshold for osmophobic association was less than 22 wt %, the threshold for fusion remained approximately 22 wt %, irrespective of the difference in the threshold for osmophobic association.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322566 TI - Time-resolved fluorometric and differential scanning calorimetric investigation of dehydroergosterol in 1-stearoyl-2-caprylphosphatidylcholine bilayers. AB - Thermal and dynamic properties of dehydroergosterol (DHE) in 1-stearoyl-2-capryl sn-glycero-3-phosphocholine [C(18):C(10)PC] have been studied by differential scanning calorimetry (DSC) and multifrequency phase-modulation fluorometry. C(18):C(10)PC is an asymmetric mixed-chain phosphatidylcholine known to form highly ordered mixed interdigitated bilayers below the maximal transition temperature, Tm, and partially interdigitated bilayers above Tm. This lipid system is thus unique in assessing the interactions between sterols and interdigitated lipid bilayers. DHE is a fluorescent analogue of cholesterol shown in previous studies to behave like cholesterol in noninterdigitated symmetric diacylphosphatidylcholines. DSC data show that DHE exhibits similar characteristics to cholesterol [Chong & Choate (1989) Biophys. J. 55, 551-556] in C(18):C(10)PC bilayers. DHE abolishes the phase transition of C(18):C(10)PC at 27 mol % compared to 25 mol % for cholesterol and decreases Tm, the onset temperature (To), and the completion temperature (Tc), at a similar rate to cholesterol at about -0.25 degrees C per mole percent DHE. Fluorescence data show that the rotational motion of DHE can be described by a hindered anisotropic model. In the gel state of C(18):C(10)PC, the rotational correlation of DHE decreases monotonically with increasing DHE content up to 24 mol %, suggesting that DHE causes a disordering/spacing effect on the packing of mixed interdigitated C(18):C(10)PC bilayers. The rotational correlation time undergoes an abrupt increase from 24 to 27 mol % DHE. Abrupt changes in the DSC parameters were also observed in the neighborhood of 27 mol %, suggesting that major reorganization takes place around this concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322567 TI - The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. AB - Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a lambda gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu160----His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a lambda max at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation (turnover number of 15 min-1) and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, the former of which appeared to correlate with human microsomal coumarin 7-hydroxylase activity. A more striking correlation was found between IIA mRNA and enzyme activity. The rat antibody was able to completely abolish coumarin 7-hydroxylase activity in 12 liver samples. In addition, kinetics of coumarin metabolism in two livers were monophasic over the substrate concentration tested. Km values obtained from human liver (2.3 microM) were similar to those obtained from lysates of hepatoma cells expressing IIA3 (3.6-7.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322568 TI - Structure and in vitro transcription of the rat CYP2A1 and CYP2A2 genes and regional localization of the CYP2A gene subfamily on mouse chromosome 7. AB - The CYP2A1 and CYP2A2 genes code for hepatic steroid hydroxylases and differ in their development regulation and expression in male and female rats. In order to explore the mechanism of regulation of these two genes, both genes were isolated and sequenced, their upstream regions compared, and their promoters transcribed in a cell-free system derived from liver. The CYP2A1 gene was completely sequenced and spanned 12,835 bp. The CYP2A2 gene was sequenced except for 1.5 and 12 kbp in the second and fifth introns, respectively. This gene was about 10 kbp longer than CYP2A1. Both genes possess nine exons that displayed overall 93% nucleotide similarity. DNA 4544 and 5529 bp upstream from the CYP2A1 and CYP2A2 genes, respectively, was also sequenced, and the transcription start sites were determined. Both genes had typical TATA boxes but did not contain CCAAT boxes within -100 bp of their polymerase start sites. CYP2A1, however, contained a reverse CCAAT box between -85 and -90. Search of the Gene Bank revealed a 255 bp region that lies -3 kbp upstream from the transcription start site of CYP2A1 displaying similarity with retrovirus polymerase. Two regions upstream of CYP2A2 were also found that displayed 90% sequence similarity with the consensus long interspersed middle repetitive element (LINE). In addition, an unusual 1.6 kbp inserted sequence was detected between -165 and -1779 bp upstream of the CYP2A2 gene that appears to be a retropseudogene. A nuclear extract derived from adult hepatocytes was used to direct in vitro transcription of the CYP2A1 and CYP2A2 gene promoters. Both genes were accurately transcribed in extracts derived from livers of male and female rats. This result is surprising in view of the fact that the CYP2A1 gene is expressed in adult female rats while the CYP2A2 gene is expressed exclusively in adult males. The CYP2A1 promoter was more actively expressed in both extracts than that of CYP2A2. By analyzing the segregation pattern of CYP2A genes in backcross offspring from an interspecies cross between the laboratory strain NFS/N and the wild mouse Mus musculus musculus, the Cyp2a subfamily was mapped proximal to the Gpi-1 locus near the centromere on chromosome 7. PMID- 2322569 TI - Structural homologies of component C5 of human complement with components C3 and C4 by neutron scattering. AB - The complement component C5 is one of a family of structurally related plasma proteins that includes components C3 and C4. Activation of C5 is the initial step in the formation of the membrane attack complex of complement. Analysis of the solution structure of C5 and comparisons with similar analyses of the structures of C3 and C4 are reported here. Neutron solution scattering gave an Mr for C5 of 201,000, which demonstrates that C5 is monomeric in solution. The radius of gyration RG of C5 at infinite contrast is 4.87 nm and corresponds to an elongated structure. The longest length of C5 was determined to be at least 15-16 nm from three calculations on the basis of the RG, the scattering intensity at zero angle I(0), and the indirect transformation of the scattering curve into real space. Comparison of the RG and contrast variation data and indirect transformations of the scattering curves for C3, C4, and C5 show that these have very similar structures. Comparisons of the C5 scattering curve with Debye small-sphere models previously employed for C4 and C3 show that good curve fits could be obtained. Unlike previous studies that have suggested significant differences, these experiments indicate that, while C5 differs from C3 and C4 in its activation and inactivation pathways, significant structural homology exists between the native proteins, as might be predicted from their high (and similar) sequence homology. PMID- 2322570 TI - Mode of assembly of amphipathic helical segments in model high-density lipoproteins. AB - The structure of discoidal apo A-I-phospholipid complexes, representing the metabolic precursors of mature high-density lipoprotein particles, was studied by a combination of both a theoretical and an experimental approach. The secondary structure of the complex was determined by circular dichroic measurements, while the relative orientation of the apo A-I helical segments and of the phospholipid acyl chains was determined by ATR infrared measurements. Fluorescence energy transfer between the tryptophan residues of apo A-I and fluorescent phospholipid probes yielded an estimation of the relative topography of the lipid and apolipoprotein components in discoidal and spherical particles. The theoretical approach consisted of the identification of the helical segments in various apo A I species. These segments were then oriented at a lipid/water interface by minimization of their hydrophobic and hydrophilic transfer energies. The calculation of the hydrophobicity profiles along the axis of the helices leads to the identification of specific interactions between pairs of helices. The helices were further assembled together with the phospholipids by computer modelling, enabling an estimation of the dimensions of the complex. The combination of the experimental and theoretical results yielded a model for discoidal apolipoprotein phospholipid complexes, in which the amphipathic helical segments are oriented along the edges of the discs. Such a model can be extended to the conversion of these complexes into mature spherical HDL, through the formation of a cholesteryl ester core. PMID- 2322571 TI - Experimental nephrotic syndrome: removal and tissue distribution of chylomicrons and very-low-density lipoproteins of normal and nephrotic origin. AB - Lymph chylomicrons and plasma VLDL, 14C-labelled in vivo, were isolated from normal and nephrotic rats and injected into normal or nephrotic recipients. In normal recipients, the half-life of chylomicrons of nephrotic vs. normal origin was significantly longer (5.2 +/- 0.5 vs. 3.5 +/- 0.4 min-1). The nephrotic chylomicrons were larger in size, deficient in apo-E and apo A-I, rich in triacylglycerol and cholesterol, but poor in phospholipids, indicating that factors related to composition affected their removal. The half-life of nephrotic vs. normal VLDL, given to normal recipients, was unexpectedly shorter, (4.5 +/- 0.2 vs. 5.8 +/- 0.2 min-1). The nephrotic VLDL were also triacylglycerol- and cholesterol-rich and phospholipid-poor, but had a large diameter spread and contained a dense fraction according to the zonal ultracentrifugation pattern, suggesting the presence of faster removable IDL-like particles. When nephrotic rats received normal particles, a pronounced removal delay was seen, paralleling the extent of plasma triacylglycerol elevation. The half-life of chylomicrons was 8.3 +/- 1.4 and 15.2 +/- 2.5 min-1 in moderately and severely nephrotic rats, respectively, that of VLDL was 11.72 +/- 2.1 and 37.8 +/- 7.1 min-1 correspondingly. The chylomicron-triacylglycerol uptake was reduced both by adipose tissues and muscles of normal or nephrotic recipients, with some increase in entry into lungs, kidneys and spleen. Tissue distribution patterns of VLDL triacylglycerol was similar to that of chylomicrons, except that the liver took up approx. 90% of the label. The low share of triacylglycerol uptake by tissues rich in lipoprotein lipase indicates that the activity of this enzyme was unlikely to limit the rate of removal. Lipoprotein lipase activity in adipose tissue and heart was slightly decreased in moderately nephrotic rats and declined only by approx. 35% in severely nephrotic ones. These results indicate that the removal defect in nephrosis seems to be due, in part, to changes in the composition of triacylglycerol-rich particles, compromising their accessibility to lipolysis and, in part, to their abundance, saturating the lipolytic capacity. PMID- 2322572 TI - Acid lipase in rat intestinal mucosa: physiological parameters. AB - Previous studies have shown that up to a half of infused triacylglycerol does not exit the intestine via lymphatics. This suggests the presence of a mucosal lipase which could provide fatty acids for potential transport via the portal vein. The present study describes an acid-active lipase in rat intestinal mucosa. Acid lipase was assayed using a glyceryl tri[14C]oleate emulsion (pH 5.8). Mucosal homogenates were differentially centrifuged to yield cellular organelles and cytosol. Cells were sequentially released from villi using citrate and EDTA. The enzyme was found to be most active in the proximal quarter intestine and in the upper third of villi. Its greatest activity was in the lysosomal fraction. Esophageal diversion demonstrated that lingual lipase was not the precursor of the mucosal acid lipase. Bile salts stimulated activity 3- to 5-fold, but other neutral or anionic detergents were inhibitory. Of the detergents tested, taurocholate at super critical micellar concentrations could restore activity only with SDS. Sepharose 6B chromatography suggested that the enzyme partitioned into an SDS and taurocholate mixed micelle. We conclude that mucosal acid lipase is a distinct, intrinsic enzyme of the intestinal mucosa. It is predominantly lysosomal in origin. The location of its greatest activity in the villus tips of the proximal intestine suggests that it is potentially involved in mucosal triacylglycerol disposal. PMID- 2322574 TI - Biotinyl-high-density lipoproteins as a probe for the determination of high density lipoprotein turnover in humans. AB - A simple and reliable method has been developed for the determination of high density lipoprotein (HDL) turnover in humans. In this method, complex formation of [14C]methylavidin with biotinyl-HDL3 and subsequent precipitation of excess [14C]methylavidin with biotinyl-silica-gel is utilized for the detection of as little as 0.1 microgram of biotinyl-HDL3 (by protein)/ml of serum with high precision and reproducibility, at 7.9 +/- 0.9% (n = 7) of the peptidyl lysine modified. In serial dilutions and quadruplicate determinations the intra- and interassay variations were less than 4.7% and 5.2%, respectively (n = 5). Recovery of biotinyl-HDL3 averaged 92 +/- 5.7% throughout the working range of the assay (n = 4). Variations in the levels of HDL or very-low-density lipoprotein (VLDL) did not interfere with the measurement of biotinyl-HDL3 in serum. Also, results were not affected by storage of serum samples at -80 degrees C for up to 4 weeks. After reinjection of autologous biotinyl-HDL3 (0.12 mg protein/kg body wt.) into five normolipidemic male volunteers, typical decay curves were obtained. The mean half-life of biotinyl-HDL3 was 5.1 +/- 0.5 days, no different from that reported for radiolabeled HDL or radiolabeled HDL apolipoproteins. Routine immunobinding analysis did not reveal formation of antibodies with specificity towards HDL 4 weeks after the reinjection studies. From this it appears that biotinyl-HDL3 is a suitable probe and a safe and reliable alternative for the determination of HDL turnover in humans when application of radiolabeled HDL is not desirable. PMID- 2322573 TI - Behaviour of phospholipase-modified HDL towards cultured hepatocytes. I. Enhanced transfers of HDL sterols and apoproteins. AB - Human HDL subfractions (HDL2, HDL3, or HDL separated by heparin affinity chromatography) were labelled either on their apolipoprotein moiety with 125I or on their sterols: unesterified [14C]cholesterol and [3H]cholesteryl linoleyl ether, a non-hydrolysable analog of esterified cholesterol. HDL subfractions were then treated with or without phospholipase A2 from Crotalus adamanteus in presence of albumin leading to a 72-82% phosphatidylcholine degradation. Control and treated HDL were reisolated and then addressed to cultured rat hepatocytes. (A) During incubations, unesterified [14C]cholesterol from HDL3 readily appeared in hepatocytes. The specific uptake of HDL esterified cholesterol calculated from [3H]cholesteryl ether was 2-4-times less important. Uptake of HDL cholesterol tended to saturate at 150-200 micrograms/ml HDL protein. A prior phospholipase treatment of HDL3 stimulated by 2-5-fold the uptake of [3H]cholesteryl ether, whereas the transfer of free [14C]cholesterol was minimally increased. The uptake of 3H/14C-labelled sterols from HDL2 was 2-3-times higher than from HDL3. (B) Parallel experiments were conducted with 125I-labelled HDL subfractions. At 37 degrees C, the specific uptake and degradation of HDL3 125I-apolipoprotein were about 2-fold enhanced following treatment of HDL3 with phospholipase A2. Uptakes of apolipoprotein and of esterified cholesterol were compared, indicating a preferential delivery of the sterol over apoprotein (X5). The dissociation was still more pronounced with phospholipase-treated HDL3. Competition experiments showed that 12-times more unlabelled HDL3 were required to half reduce the uptake of HDL3 [3H]cholesteryl ether than to impede similarly the HDL 125I apolipoprotein recovered in cells. Uptake of 125I-labelled apolipoprotein from HDL2 was quantitatively comparable to that from HDL3. (C) Binding of 125I-HDL subfractions was followed at 4 degrees C. A specific binding was observed for HDL2 and HDL3, although kinetic parameters were quite different (KD of 9 and 25 micrograms/ml, respectively). Following phospholipolysis, both the specific and non-specific contributions to total binding were increased. Hence, hepatocytes take up more 125I-labelled apolipoprotein and 3H/14C-labelled sterols from lipolysed HDL than from unmodified particles. This is associated to changes in the binding characteristics. PMID- 2322575 TI - Functional analysis of multiple promoters of the rat insulin-like factor II gene. AB - We have characterized the multiple promoters of the rat insulin-like growth factor II (rIGFII) gene by in vivo transient expression assay using a series of deletion mutant templates. Among the four promoters (P1, P2, P3 and P6), two (P2 and P3) showed relatively strong promoter activities compared with the other two. One of the four promoters, P2, was further characterized by gel band-shift and footprinting analysis using HeLa cell nuclear extract, showing two retarded bands and at least one protected sequence stretch. The results indicated that P2 has a very simple structure like P3, and consists of no more than 141 base-pairs (bp) including a TATA box and two GC core hexanucleotides. Promoter strength shown by in vivo transient expression in different cell types failed to explain the differential employment of P2 and P3 in these cells, suggesting the involvement of other regulatory mechanisms that might operate only in the native state. PMID- 2322576 TI - Intracellular fate of fibrinogen B beta chain expressed in COS cells. AB - Full-length fibrinogen B beta cDNA was subcloned into an expression vector, pBC12BI, and transfected into COS cells. B beta chain expression was measured by pulse-labelling cells with L-[35S]methionine, immunoprecipitating the B beta chain with antibody to fibrinogen and separating the nascent radioactive protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). B beta chain was expressed in transfected COS cells but was not secreted into the medium. Treatment with endoglycosidase H showed that non-secreted B beta chain contains mannose-rich carbohydrates rather than the complex form of carbohydrate which occurs in plasma fibrinogen and indicates that B beta chain is not transported to the Golgi apparatus. In transfected COS cells, antibody to fibrinogen co-immunoprecipitated B beta chain and 78 kDa immunoglobulin-binding protein (BiP) and antibody to BiP immunoprecipitated BiP and nascent B beta chains. Non-secreted B beta chain was degraded intracellularly with a half-life of 5 h by enzymes which were not affected by incubating transfected cells with NH4Cl, which indicates a non-lysosomal pathway of degradation. These studies indicate that B beta chain by itself does not contain the signal for fibrinogen secretion and that non-secreted B beta chain is associated with BiP and degraded in the rough endoplasmic reticulum. PMID- 2322577 TI - Synthesis of EF-Tu and distribution of its mRNA between stroma and thylakoids during the cell cycle of Chlamydomonas reinhardii. AB - In Chlamydomonas reinhardii the elongation factor EF-Tu is encoded in the chloroplast DNA. We identified EF-Tu in the electrophoretic product pattern of chloroplast-made proteins and showed that this protein is only synthesized in the first half of the light period in synchronized cells. The newly synthesized EF-Tu contributed little to the almost invariable content of EF-Tu in chloroplasts during the light period of the cell cycle. However, increasing cell volume and the lack of EF-Tu synthesis in the second half of the light period led to a decrease in the concentration of EF-Tu in chloroplasts. At different times in the vegetative cell cycle, the RNA was extracted from whole chloroplasts and from free and thylakoid-bound chloroplast polysomes. The content of mRNA of EF-Tu in chloroplasts and the distribution between stroma and thylakoids were determined. During the light period, the content of the mRNA for EF-Tu varied in parallel to the rate of EF-Tu synthesis. However, in the dark, some mRNA was present even in the absence of EF-Tu synthesis. Most of the mRNA was bound to thylakoids during the whole cell cycle. This suggests that synthesis of EF-Tu is associated with thylakoid membranes. PMID- 2322579 TI - Modification of the accessibility of ribosomal proteins after elongation factor 2 binding to rat liver ribosomes and during translocation. AB - Free- and EF-2-bound 80 S ribosomes, within the high-affinity complex with the non-hydrolysable GTP analog: guanylylmethylenediphosphonate (GuoPP(CH2)P), and the low-affinity complex with GDP, were treated with trypsin under conditions that modified neither their protein synthesis ability nor their sedimentation constant nor the bound EF-2 itself. Proteins extracted from trypsin-digested ribosomes were unambiguously identified using three different two-dimensional gel electrophoresis systems and 5 S RNA release was checked by submitting directly free- and EF-2-bound 80 S ribosomes, incubated with trypsin, to two-dimensional gel electrophoresis. Our results indicate that the binding of (EF-2)-GuoPP[CH2]P to 80 S ribosomes modified the behavior of a cluster of five proteins which were trypsin-resistant within free 80 S ribosomes and trypsin-sensitive within the high-affinity complex (proteins: L3, L10, L13a, L26, L27a). As for the binding of (EF-2)-GDP to 80 S ribosomes, it induced an intermediate conformational change of ribosomes, unshielding only protein L13a and L27a. Quantitative release of free intact 5 S RNA which occurred in the first case but not in the second one, should be related to the trypsinolysis of protein(s) L3 and/or L10 and/or L26. Results were discussed in relation to structural and functional data available on the ribosomal proteins we found to be modified by EF-2 binding. PMID- 2322578 TI - Modification of the reactivity of three amino-acid residues in elongation factor 2 during its binding to ribosomes and translocation. AB - The accessibility of three amino acids of EF-2, located within highly conserved regions near the N- and C-terminal extremities of the molecule (the E region and the ADPR region, respectively) to modifying enzymes has been compared within nucleotide-complexed EF-2 and ribosomal complexes that mimic the pre- and posttranslocational ones: the high-affinity complex (EF-2)-nonhydrolysable GTP analog GuoPP[CH2]P ribosome and the low-affinity (EF-2)-GDP-ribosome complex, EF 2 and ribosomes being from rat liver. We studied the reactivity of two highly conserved residues diphthamide-715 and Arg-66, to diphtheria-toxin-dependent ADP ribosylation and trypsin attack, and of a threonine that probably lies between residues 51 and 60, to phosphorylation by a Ca2+/calmodulin-dependent protein kinase. Diphthamide 715 and this threonine residue were unreactive within the high-affinity complex but seemed fully reactive in the low-affinity complex. Arg 66 was resistant to trypsin in both complexes. The possible involvement of the E and ADPR regions of EF-2 in the interaction with ribosome in the two complexes is discussed. PMID- 2322580 TI - Lipoprotein lipase mRNA expression in brown adipose tissue: translational and/or posttranslational events are involved in the modulation of enzyme activity. AB - Lipoprotein lipase mRNA abundance in rat brown adipose tissue increases during the first 24 h of cold exposure. Lipoprotein lipase mRNA levels do not change in brown fat throughout pregnancy and lactation, whereas enzyme activity is significantly lowered. After 5 h of acute cold or noradrenaline administration there is a 2-fold increase in lipoprotein lipase mRNA abundance, whereas lipoprotein lipase activity is stimulated to more than 6-fold the basal values. It is concluded that translational and/or posttranslational mechanisms are involved in the noradrenergic modulation of lipoprotein lipase activity in brown fat. PMID- 2322581 TI - Basic nuclear proteins of the histone-less eukaryote Crypthecodinium cohnii (Pyrrhophyta): two-dimensional electrophoresis and DNA-binding properties. AB - Unlike typical eukaryotes, the Dinoflagellate Crypthecodinium cohnii does not contain histones but six major basic, low molecular weight nuclear proteins which represent only 10% of the DNA mass and differ from histones in their electrophoretic and DNA-binding properties. These proteins are resolved in two dimensional electrophoresis (AUT-PAGE x SDS-PAGE). Three proteins with an apparent molecular mass of 16, 16.5 and 17 kDa (p16, p16.5 and p17) are present in addition to the major 14 kDa basic nuclear component (HCc). HCc itself is resolved in three proteins (alpha, beta and gamma). When the proteins are not reduced with 2-mercaptoethanol before 2D-PAGE, the migration of HCc alpha, beta and gamma is modified in a way which suggests the formation of both inter- and intramolecular disulfide bridges and thus, the presence of at least two cysteines. The amino-acid analysis of HCc proteins resolved in 2D gels confirms that they are lysine-rich. HCc alpha, beta and gamma as well as p16, p16.5 and p17 are removed from isolated chromatin with 0.6 M NaCl, indicating that their affinity for DNA in vivo is lower than that of core histones. Furthermore, in vitro, they bind more tightly to single-stranded than to double-stranded DNA. PMID- 2322582 TI - Comparative analysis of 5.8 S rRNA from Ephedra kokanica Regl. (Gymnospermae) and other plant species. AB - 5.8 S rRNA from the gymnosperm Ephedra kokanica Regl. (EMBL Data Library accession No. X15676) has been sequenced. It is 161 nucleotides long and contains three 2'-O-methylated residues--two adenosines and one guanosine. No pseudouridine have been detected. E. kokanica 5.8 S rRNA, as those from other plant species, can form a secondary structure with paired 5'- and 3'-terminal regions. 5.8 S rRNAs of seed plants differ from the moss Mnium reguicum 5.8 S rRNA in that they have longer variable 'GC-rich' hairpins with insertions in the loop region. 5.8 S rRNA of E. kokanica reveals 69 and 82% of homology with that of moss and five angiosperm species, respectively. The posttranscriptional modification pattern of plant 5.8 S rRNAs is not strictly conservative. PMID- 2322583 TI - Isolation and characterization of clones for the rat hepatic lipase gene upstream regulatory region. AB - Genomic clones for 2287 nucleotides of the 5' flanking region, 135 nucleotides of the first exon, and 283 nucleotides of the first intron of the hepatic lipase gene were characterized. The predominant start site for transcription was identified by primer extension and S1 nuclease analyses to be 50 bases upstream of the ATG initiation codon. Based on the location of the major transcription start site, the functional TATA box is located 29 nucleotides upstream. Putative response elements for AP-2, cAMP, OCT-1, C/EBP, estrogen, glucocorticoids, sterols and thyroid hormone were located in this gene. Also a putative liver specific element for apolipoproteins, C3P, was identified. PMID- 2322584 TI - The nucleotide and deduced amino acid sequences of a cDNA encoding a new species of pregnancy-specific beta 1-glycoprotein (PS beta G). AB - We screened a cDNA library of a human placenta with cDNA for nonspecific cross reacting antigen, a member of the carcinoembryonic antigen gene family. One of the positive clones, PS34, was found to encode a 426 amino acid protein belonging to pregnancy-specific beta 1-glycoprotein (PS beta G). The mature PS34 protein consisted of domains, N, A1, A2, B2 and C. The domain-N of PS34 showed sequence similarities of 79.8-83.5% to those of the PS beta G members so far reported, indicating PS34 is a new member of PS beta G and also of the carcinoembryonic antigen gene family. PMID- 2322585 TI - Effect of chronic ethanol administration on total asialoglycoprotein receptor content and intracellular processing of asialoorosomucoid in isolated rat hepatocytes. AB - Chronic ethanol administration markedly impairs the process of receptor-mediated endocytosis (RME) of a representative asialoglycoprotein, asialoorosomucoid (ASOR), by the liver (Casey et al. (1987) J. Biol. Chem. 262, 2704-2710). Decreased surface binding was the major defect reported in our initial study, along with impaired internalization and degradation of 125I-ASOR in chronically fed ethanol animals. In this study, we further characterized these impairments by examining the content of intracellular receptors and by investigating ligand processing directed by these intracellular receptors. Ethanol administration for 5-7 weeks decreased intracellular ASOR receptor content by 40%, a result which was confirmed by using both a ligand-binding assay and an antibody-binding assay. In addition to a decreased number of intracellular receptors, an impairment in intracellular processing of receptor-ligand complexes was identified. In ethanol fed animals, dissociation of receptor-ligand complexes was decreased during steady-state conditions of endocytosis at 37 degrees C. Impaired receptor-ligand dissociation did not alter the fate of the ligand which was to undergo diacytosis (ligand recycling), but did appear to impair degradation of intracellular ligand. These results indicate that chronic ethanol administration decreases ligand binding due to a decreased number of receptors and impairs intracellular processing of ASOR in hepatocytes. PMID- 2322586 TI - The transport of L-glutamine into cultured human fibroblasts. AB - The transport of L-glutamine has been studied in diploid human fibroblasts in culture. Mathematical discrimination by nonlinear regression, competition analysis, and conditions varying the relative contribution of the various mediations have been used to characterize the systems engaged in the inward transport of this amino acid. The adopted criteria showed that L-glutamine enters the fibroblast by the Na(+)-dependent systems ASC and A and by a Na(+) independent route identified as system L. The relative contribution of these agencies to the total saturable uptake of glutamine varied with the concentration of the amino acid and with the nutritional state of the cell. At amino acid concentrations approaching those encountered in human plasma: (1) system ASC represented the primary mediation for entry of L-glutamine in human fibroblasts; (2) the contribution of system A was lower, though significant, in unstarved repressed cells and became predominant in starved derepressed cells; (3) the Na(+)-dependent system L accounted for less than one-fifth of glutamine uptake in either nutritional condition. The changes in the relative contribution of the various systems to the uptake of glutamine as a function of its concentration may have implications in pathophysiology under conditions associated with enhanced glutamine concentrations in the extracellular fluids. PMID- 2322587 TI - Whole-cell K+ currents in type II pneumocytes freshly isolated from rat lung: pharmacological evidence for two subpopulations of cells. AB - The patch clamp technique was used to record whole cell K+ currents in type II pneumocytes freshly isolated from adult rats. Depolarizing voltage steps evoked outward K+ currents which were distinguished into low and high threshold types, only one type being apparent in any one cell. Low-threshold (LT) currents were activated at test potentials of -40 mV to -20 mV and were reduced in amplitude by 20 mM tetraethylammonium (TEA). High-threshold (HT) currents were activated only at test potentials positive to -20 mV and current noise was always greater than for LT currents. HT currents were also significantly more sensitive than were LT currents to block by TEA. Quinine (1 mM) blocked LT currents reversibly at all activating test potentials. HT currents were also reversibly blocked by 1 mM quinine, but in a voltage-dependent manner, the degree of block increasing with increasing test potential. 4-Aminopyridine (2 mM) further distinguished the two current types: it was virtually without effect on HT currents but caused large reductions in LT current amplitudes, apparently by acting on the open channels underlying this current. These data clearly distinguish type II pneumocytes into two subpopulations and suggest that they may play separate roles in the functioning of the intact alveolar epithelium. PMID- 2322589 TI - Developmental increases in the inwardly-rectifying K+ current of embryonic chick ventricular myocytes. AB - Whole-cell and single-channel inwardly-rectifying K+ currents (IK1) of early (3 day-old) and late (17-day-old) embryonic chick ventricular myocytes were compared to ascertain whether there are developmental changes in the properties of this conductance. The magnitude of the IK1 conductance in the early myocytes was small, but it was increased about five-fold in the older embryonic myocytes. It was found that the density of inwardly-rectifying K+ channels was greater (in the surface membrane) of the 17-day than in the 3-day embryonic myocyte. In addition, the single channel conductance for 17-day myocytes was several-fold larger than for the 3-day myocytes. These results suggest that cardiac inward rectifier channels may not only proliferate in number, but may also undergo structural alterations during development. PMID- 2322588 TI - Solubilization of thiazide diuretic receptors from rat kidney membranes. AB - Thiazide-type diuretics act at receptors to inhibit NaCl transport in the renal distal tubule. We solubilized high-affinity [3H]metolazone binding sites from rat kidney membranes with Triton X-100, which was more effective than several other detergents. Phosphatidylcholine and a mixture of proteinase inhibitors were needed to stabilize binding so that 57% of solubilized binding remained after 72 h at 4 degrees C. The affinities of solubilized (Kd = 11.4 +/- 0.5 nM) and membrane-bound receptors (Kd = 12.0 +/- 1.7 nM) were similar. The maximal number of binding sites/mg protein of solubilized receptors was 46 +/- 3% (n = 5) of membrane-bound receptors. Diuretics with a wide range of affinities had similar affinities for the solubilized and membrane-bound sites. Chloride inhibited and sodium stimulated the binding of [3H]metolazone to solubilized receptors, as they do with membrane-bound receptors. These studies demonstrate that, as judged by ligand binding, thiazide receptors can be solubilized in an active conformation and provide the basis for future purification and reconstitution. PMID- 2322590 TI - Ca2(+)-induced secretion by electropermeabilized human neutrophils. The roles of Ca2+, nucleotides and protein kinase C. AB - Studies of stimulus-response coupling have benefitted from the availability of permeabilization techniques, whereby putative second messengers and intracellular modulators can be introduced into the cell interior. Electropermeabilization, which uses high-intensity electric fields to breach the plasma membrane, creates small pores, permitting access of solutes with molecular masses below 700 KDa. Neutrophils permeabilized by this technique, but not intact cells, discharged lysosomal constituents when exposed to micromolar levels of Ca2+. Secretion by electroporated neutrophils was significantly enhanced by the presence of Mg-ATP (0.3-1.0 mM). Contrary to expectations, it was determined that ATP was not the only nucleotide which enhanced Ca2(+)-induced secretion in the presence of Mg2+. Not only could GTP, XTP, ITP, UTP or ADP partially or completely replace ATP, but even non-hydrolyzable nucleotides such as ADP beta S ATP gamma S, and App[NH]p were effective. GTP gamma S and GDP beta S were inhibitory, while Gpp[NH]p was inactive. None of these nucleotides induced secretion on its own. In contrast, neutrophils which were permeabilized and then washed, were only slightly activated by Mg-ATP and other nucleotides; even the response to Ca2+ alone was less. This hyporesponsiveness of washed cells proved to be due to a time dependent deactivation of the permeabilized neutrophils taking place at 4 degrees C. In an effort to assess the role for protein kinase C (PKC) in secretion in this system, we examined the effects of phorbol myristate acetate (PMA), a PKC agonist. PMA enhanced degranulation induced by Ca2+ by lowering the requirement for this divalent cation; enhancement by PMA was not dependent upon exogenous ATP. Three inhibitors of PKC with varying specificity, namely H-7, K-252a, and staurosporine, all abrogated PMA-enhanced secretion. These agents also inhibited secretion stimulated by Ca2+ plus ATP in parallel with that induced by Ca2+ plus PMA, strongly suggesting a role for PKC in modulation of degranulation by ATP. Our results show that electropermeabilized neutrophils provide a convenient, useful model for stimulus-secretion coupling. These data also suggest that the 'requirement' for Mg-ATP, which has been observed in other permeabilized cell systems, is not simply for metabolic energy or as a substrate for kinases. It is possible that these nucleotides all interact with a recently described neutrophil receptor for adenine nucleotides or with a recently postulated exocytosis-linked G-protein. PMID- 2322591 TI - Unusual specificity of the androgen receptor in the human prostate tumor cell line LNCaP: high affinity for progestagenic and estrogenic steroids. AB - LNCaP tumor cells, derived from a metastatic lesion of a human prostatic carcinoma, are androgen-sensitive in cell culture. Although increase in growth rate is observed with low doses of progestagens or estradiol, these cells contain exclusively androgen receptors. In the present study the binding affinity of different ligands for both non-DNA- and DNA-binding (transformed) forms of the androgen receptor were analyzed. The cytosolic (non-transformed) form of the receptor displayed an abnormal high affinity for progestagens and estradiol when compared with the cytosolic androgen receptor from other sources. Subsequently the non-transformed forms of the androgen receptor obtained from LNCaP cell nuclei was studied. A high binding affinity was found not only for dihydrotestosterone, but also for progesterone and the synthetic progestagen R5020 (relative binding affinity 42% and 10% of dihydrotestosterone). The binding characteristics of the transformed androgen receptor were examined in intact cells at 37 degrees C. LNCaP cells were compared in this respect with COS cells containing the cloned human androgen receptor, normal human skin fibroblasts and PC3 (prostate) and NHIK (cervix) human tumor cell lines. The affinity of the transformed androgen receptors for the progestagen R5020 in LNCaP cells was significantly higher than in the other cell systems, although the differences were less pronounced than for the non-transformed receptor form. IN CONCLUSION: the LNCaP tumor cells contain an androgen receptor with an abnormal binding site. This might be due to a mutation and/or a post-transcriptional effect. PMID- 2322592 TI - Endogenous protein phosphorylation in purified plant mitochondria. AB - Purified mitochondria from potato (Solanum tuberosum L. cv Bintje) tubers were incubated with [gamma-32P]ATP. Total 32P incorporation into proteins saturated after about 2 min and showed a Km (ATP) of 0.2 mM and a broad pH optimum of 6.5 8. About 30 polypeptides were labelled as shown by SDS-PAGE and autoradiography. The major labelled polypeptides were at 11, 14, 16 22-23, 40, 42 (the alpha subunit of the pyruvate dehydrogenase complex), 45-46, 60, 62, 69, 84-86 and 97 kDa. By the use of atractylate, EGTA and trypsin the major phosphoproteins of 40 and 42 kDa and possibly some minor phosphoproteins in the range 26-33 kDa were localized to the matrix or the inner surface of the inner membrane. All other labelled polypeptides as well as (at least) two kinases (one Ca2(+)-dependent, the other Ca2(+)-independent) are outside the inner membrane. PMID- 2322593 TI - Biotransformation of mafosfamide in P388 mice leukemia cells: intracellular 31P NMR studies. AB - The intracellular transformation of cis-mafosfamide has been studied in P388 mice leukemia cells using 31P-NMR spectroscopy. For this purpose the cells were entrapped in low-gelling-temperature agarose threads. Internal pH of the cells, determined from the position of the intracellular inorganic phosphate, was 7.2. The cell membrane was permeable to 4-hydroxycyclophosphamide and aldophosphamide and less permeable to phosphoramide mustard. 4-Ketocyclophosphamide and carboxyphosphamide signals were not detectable in cells either sensitive or resistant to oxazaphosphorine treatment. PMID- 2322595 TI - Binding of 125I-CCK-8 and 125I-gastrin-I to dispersed chief cells from guinea-pig stomach. AB - In dispersed gastric chief cells from guinea-pig stomach, binding of iodinated cholecystokinin octapeptide (125I-CCK-8) was relatively slow, temperature dependent, to a single class of binding sites and inhibited by various gastrin- and CCK-related agonists and receptor antagonists. Binding of iodinated gastrin-I (125I-gastrin-I) was moderately rapid, temperature-dependent, to a single class of binding sites, and inhibited by various gastrin and CCK-related agonists and receptor antagonists. Gastrin-I as well as C-terminal fragments of CCK containing from eight amino acids (CCK-8) to four amino acids (CCK-4) stimulated pepsinogen secretion and inhibited binding of 125I-CCK-8 and 125I-gastrin-I. In addition, each of five different receptor antagonists inhibited binding of 125I-CCK-8 and 125I-gastrin-I and inhibited pepsinogen secretion stimulated by CCK-8 or gastrin I. With each of eight different agonists and with each of five different antagonists the value of IC50 for inhibition of binding of 125I-CCK-8 was not significantly different from the value of IC50 for inhibition of binding of 125I gastrin-I, indicating that in gastric chief cells the sites to which 125I-CCK-8 binds are the same sites to which 125I-gastrin-I binds. With the agonists as well as with the antagonists, however, there was no consistent relationship between the ability of a particular agent to inhibit binding and its ability to modify pepsinogen secretion, indicating that in gastric chief cells the sites that bind 125I-CCK-8 and 125I-gastrin-I are not the receptors that mediate stimulation of pepsinogen secretion by CCK-8 or by gastrin-I. PMID- 2322594 TI - Lamellar bodies of cultured human fetal lung: content of surfactant protein A (SP A), surface film formation and structural transformation in vitro. AB - Lamellar bodies were isolated from dexamethasone and T3-treated explant cultures of human fetal lung, using sucrose density-gradient centrifugation. We examined their content of surfactant apoprotein A (SP-A), and their ability to form surface films and to undergo structural transformation in vitro. SP-A measured by ELISA composed less than 2% of total protein within lamellar bodies; this represented, as a minimum estimate, a 2-12-fold enrichment over homogenate. One- and two-dimensional gel electrophoresis also suggested that SP-A was a minor protein component of lamellar bodies. Adsorption of lamellar bodies to an air/water interface was moderately rapid, but accelerated dramatically upon addition of exogenous SP-A in ratios of 1:2-16 (SP-A:phospholipid, w/w). Similar adsorption patterns were seen for lamellar bodies from fresh adult rat and rabbit lung. Lamellar bodies incubated under conditions that promote formation of tubular myelin underwent structural rearrangement only in the presence of exogenous SP-A, with extensive formation of multilamellate whorls of lipid bilayers (but no classical tubular myelin lattices). We conclude that lamellar bodies are enriched in SP-A, but have insufficient content of SP-A for structural transformation to tubular myelin and rapid surface film formation in vitro. PMID- 2322596 TI - The lifetime of photosensory signals in Halobacterium halobium and its dependence on protein methylation. AB - Halobacteria spontaneously reverse their swimming direction about every 10 s. This behavioral pattern is transiently disturbed upon stimulation through sensory photosystems of different spectral sensitivity. As a result of stimulation, a single swimming interval is either prolonged (attractant response) or shortened (repellent response). Thereafter the cell returns to its autonomous reversal rhythm, i.e., it quickly adapts. Method are presented to determine the lifetime of repellent as well as of attractant cellular signals at the site of signal integration, using particular stimulation programs. Independent of the photosystem through which the signals were generated, the total lifetime of a repellent signal was 1.3 s. The decay of the signal was rapid during the first 100 ms and slow thereafter. The lifetime of an attractant signal was about 4 s and likewise did not depend on the photosystems. The degree of methylation of membrane proteins was increased by attractant stimuli and decreased by repellent stimuli. Inhibition of protein methylation by homocysteine was accompanied by a slowdown of the decay of both the repellent and attractant signal. A mutant strain with an increased demethylation also gave increased signal lifetimes. A lowered Ca2+ concentration, which activates methylation in vivo, led to shortened signal lifetimes. Methylation is proposed to be the mechanism which limits the signal lifetime and thereby allows the cells to adapt. PMID- 2322597 TI - Hepatic impairment in fetuses of preeclamptic mothers. AB - Cord blood from preeclamptic and normal gestations were analyzed for the vitamin K-dependent proteins, factors II, VII, IX, X, and protein C, and for fibrinogen and albumin. Factor II, factor IX, protein C, and albumin protein levels were reduced in the preeclamptic group, whereas there was no significant change in the fibrinogen or factor X protein levels. The data suggest that these findings are probably due to decreased synthesis and are not indicative of vitamin K deficiency. PMID- 2322598 TI - Sleep apneas and acid esophageal reflux in control infants and in infants with an apparent life-threatening event. AB - Clinical experience shows that episodes of apnea can occur during regurgitations or vomiting. We questioned whether sleep apneas could be related temporally to documented falls in esophageal pH, when no clinical symptoms of emesis are witnessed. Twenty infants admitted after an apparently life-threatening event ('ALTE') during sleep, but with no clinical symptoms of vomiting or regurgitations at the time of the event, and ten control infants were studied. All infants had occasional episodes of regurgitations. Polygraphic monitoring of state of alertness, cardiorespiratory activity and low esophageal pH was performed continuously during 1 night. The data were analyzed blindly. A total of 334 central and 36 obstructive apneas were monitored, mainly in the ALTE group, during NREM sleep. A total of 116 falls in esophageal pH below 4 units were seen in 18 infants; 50% occurred during wakefulness, and 31% in REM sleep. Arousals or body movements preceded the pH fall in 50% of the cases. Within 5 min following the reflux onset, 18 central apneas (7.2% of the apneas) were seen. There was no correlation between the duration, or the lowest values of esophageal pH measured, and the number or duration of apneas. No obstructive apnea, bradycardia or arousal followed the falls in esophageal pH. Acid esophageal reflux did not play a significant role in the development of apnea in our population. PMID- 2322599 TI - Correlation between levels of plasma adenosine triphosphate and stress to the fetus at delivery. AB - Adenosine triphosphate (ATP) and its metabolites are released from intracellular stores and levels of ATP in the plasma are affected by hypoxia and by exercise. We examined levels of plasma ATP in the fetus at the time of obstetrical delivery. The arterial (ACB), venous cord (VCB) and maternal venous blood (MVB) samples were collected immediately after clamping of the cord. ATP was determined by the bioluminescence method. The levels of plasma ATP were significantly higher in ACB than in VCB or in MVB. There were significant correlations between the levels of ATP in ACB and in VCB, between the levels in ACB and in MVB and between the levels in MVB and in VCB. In case of delivery by elective cesarean section, the levels of ATP in ACB were significantly higher than those in ACB of the fetus delivered vaginally. We found a significant correlation between the levels of plasma ATP in ACB and PO2 in VCB, though there was no significant correlation between the levels of ATP and pH and PCO2. These observations suggest that ATP in ACB may be of fetal origin, that the levels decrease concomitantly in response to stress during vaginal delivery and correlate with the oxygen supplied from the placenta. PMID- 2322600 TI - Correlation of commonly used measures of intrauterine growth with estimated neonatal body fat. AB - Several morphometric measures have been used to identify infants at greatest risk from aberrant intrauterine growth. 119 near-term infants were studied to answer the more basic question of how well measures, such as birthweight percentile, ponderal index, the body mass index and the weight/length ratio reflect body fat in the neonate. Skinfold thicknesses were measured as an estimate of fat stores. Multiple regression analysis revealed that the weight/length ratio showed the strongest correlation with relative adiposity, explaining 52% of the variance. Further, sequential exponentiation of the crown-heel length in body mass index and ponderal index decreased the correlation with estimates of body fat. The simple weight/length ratio, exhibiting both a close correlation with body fat and independence of gestational age, race and sex, in near-term infants may be the best morphometric measure of the nutritional component of intrauterine growth in the neonate. PMID- 2322601 TI - Cis- and trans-isomeric fatty acids in plasma lipids of newborn infants and their mothers. AB - The proportionate fatty acid composition of plasma lipids was determined by high resolution gas-liquid chromatography in 30 pairs of mothers and their term infants at the time of birth. Trans-fatty acids were found at similar percentage levels in maternal and infantile plasma, evidence for the first time of their placental permeability. In umbilical plasma, linoleic and alpha-linolenic acids contributed markedly smaller portions to total fatty acids, in contrast to clearly higher proportions of their long-chain polyunsaturated metabolites (LCP). Significantly larger percentage values in cord than in maternal plasma were found for those LCP that are structural components of brain lipids, which may reflect a discriminating placental transport mechanism for certain physiologically important LCP. PMID- 2322602 TI - Neutral and acidic goblet cell concentrations in the small intestine of the unweaned pig. AB - Concentrations of Alcian blue (AB+) and periodic acid-Schiff (PAS+) staining goblet cells on small intestinal villi and in intestinal glands of unweaned pigs were determined. Samples from the distal duodenum, mid jejunum, and distal jejunum were taken from 7 pigs from each of 4 litters at ages 9, 18, 24, 27, 30, 33 and 36 days. The only concentration differences between litters were observed in the mid-jejunal villi AB+ staining goblet cells (p = 0.03) so that litter origin of piglets was basically nonexistent. Concentrations of goblet cells increased with age on the villous AB+ and PAS+ cells in the duodenum and in the mid jejunum (p less than 0.03). No other differences in goblet cell concentrations were observed. PMID- 2322603 TI - Intrauterine exposure to parathion increases its disposition rate in postnatal life. AB - The effect of in utero exposure to parathion was assessed in offspring from dams treated with low doses of parathion during gestation. An analytical method to measure parathion in small blood samples (200 microliters) was used which prevented significant bleeding during sampling. Pharmacokinetic studies were performed in anesthetized 6-week-old male rats and showed a monoexponential pattern of elimination. The offspring exposed in utero to parathion depicted a higher plasma disposition rate of the insecticide than the control group (T1/2 el 60 +/- 18.2 and 24.8 +/- 13.1 min, respectively; p less than 0.05), suggesting the presence of some adaptive mechanism. This mechanism might render the in utero exposed animal less liable to the toxic effects of this pesticide during the postnatal life. The increase observed in the elimination rate does not seem to be due to higher secretory activity of the kidney, and metabolic mechanisms might be involved. PMID- 2322604 TI - Effect of hyperthermia on thyroid structure in the late gestation fetal lamb. AB - This study examined the effect of hyperthermia in late gestation on fetal thyroid structure. Mild heat stress (increase of ewe's rectal temperature to 40.4 degrees C) caused significant changes of fetal thyroid structure. Intra-follicular colloid area was significantly larger in the heat-stressed group (2,532 +/- 181 microns2) compared to a control group where rectal temperature of the ewe was within the normal range (1,660 +/- 188 microns2; p less than 0.01). Epithelial cell height was significantly reduced (2.5 +/- 0.19 vs. 4.8 +/- 0.26 microns; p less than 0.01). Fetal plasma glucose concentrations were significantly lower in the heat-stressed group (0.7 +/- 0.07 mmol/l) compared to the non-heated group (1.0 +/- 0.11 mmol/l; p less than 0.05). We suggest that the fetal thyroid gland in sheep is responsive to environmental temperature changes and is important in the neuroendocrine regulation of fetal body temperature. Fetal hypoglycaemia may also contribute to the changes in fetal thyroid gland by altering the peripheral utilization of thyroid hormone. Such changes, if prolonged, may contribute to the decreased rate of fetal growth and maturation associated with chronic heat stress in sheep. PMID- 2322605 TI - Carbon monoxide production by nonbacterial sources after heme feeding of neonatal rats. AB - We determined the relative potential for nonbacterial CO production after oral heme feeding of 12-hour-old rats. The intestinal flora was eliminated by treatment with kanamycin, ampicillin, and neomycin. CO excretion (VeCO) was measured after oral administration of heme (0.64 mumol/animal). Antibiotic treatment alone did not significantly affect the VeCO of rats gavaged with saline. Heme administration increased (p less than 0.05) the VeCO during t = 1-11 h with a peak at 3 h. Antibiotic treatment reduced this VeCO (p less than 0.05) during t = 2-8 h, but its level (peak at t = 2-3 h) was still significantly (p less than 0.05) above its nonheme control. The results confirm that bacterial degradation of heme is an important source of CO in suckling rats not pretreated with broad-spectrum antibiotics. However, oral heme feeding of gut-sterilized animals yielded transiently significantly increased VeCO. HO-mediated degradation of enteral heme is a likely nonbacterial source of CO and possibly bilirubin in the neonate. PMID- 2322606 TI - Morphometrical studies on perinatal development of glomerular components in rat. AB - Perinatal development of rat glomerulus was studied morphometrically. The percentage volumes of the five glomerular components (epithelial cells, capillary, mesangium, glomerular basement membrane, and Bowman's space) were determined by point counting and the surface area of glomerular basement membrane per unit volume of glomerulus was done by intercept counting. Percentage volume of Bowman's space was significantly decreased between days 20 and 21 of gestation, indicating the rapid growth of glomerular tuft during the prenatal period. Though both the length of glomerular capillary per unit volume of glomerulus (Lv) and surface area of glomerular basement membrane per unit volume of glomerulus were gradually increased from fetal day 20 to neonatal day 3, remarkable increase in Lv was observed between fetal day 22 and neonatal day 1. This indicates that the rat glomerulus develops rapidly during this period to adapt to extrauterine environment after birth. PMID- 2322607 TI - Furosemide increases total calcium in kidney and cytoplasmic free calcium in blood mononuclear cells of guinea pigs. AB - Nephrocalcinosis has been observed in premature infants treated with furosemide. To see whether furosemide-induced renal calcium accumulation is reflected in easily accessible extrarenal cells, we measured cytosolic free calcium ([Ca2+]i) in blood mononuclear cells and kidney tissue calcium of guinea pigs chronically treated with furosemide. At week 0, the mean [Ca2+]i in blood mononuclear cells using the fluorescent indicator quin2 was 105 +/- 4 nM. After 2 weeks of treatment with furosemide, the high dosage (10 or 20 mg/kg/day) caused a significant increase in [Ca2+]i. There was no change in cell volume after 1 or 2 weeks of treatment with furosemide at this dosage. The kidney total calcium concentration and histological calcium accumulation increased with increasing furosemide dosages. These observations suggest that calcium accumulation in blood mononuclear cells may reflect the calcium accumulation in the kidney after furosemide treatment. PMID- 2322608 TI - 1,25(OH)2D3 stimulates phospholipid biosynthesis and surfactant release in fetal rat lung explants. AB - Lung tissue from 18-day-old rat fetuses was cultured in the presence of 1,25 dihydroxyvitamin D3 - 1,25(OH)2D3 - (10(-9) M) and dexamethasone (10(-7) M) for 48 h. 1,25(OH)2D3 increased the lung content in phospholipids more specifically related to lung surfactant, phosphatidylcholine and phosphatidylglycerol. This increase was similar to that observed with dexamethasone. In addition, unlike dexamethasone, 1,25(OH)2D3 stimulated the surfactant release into luminal spaces, as evidenced by light and electron microscopy. Thus, vitamin D3 might represent an additional factor controlling fetal lung maturation by stimulating phospholipid synthesis and surfactant release from type II cells. PMID- 2322609 TI - Group-specific component in neonatal breast secretion: relationship to the cellular content. AB - Group-specific component (Gc) and total albumin concentrations in the breast secretions from 20 full-term infants were measured. The Gc concentrations as well as the albumin concentrations correlated significantly (p less than 0.02) with the total cell count and the absolute concentration of each white blood cell type in the breast fluid. The ratio of albumin in neonatal breast secretion to that in neonatal serum was similar to the comparable ratio for Gc. Since albumin and Gc are of similar molecular size, these observations suggest leakage of these two proteins from serum to breast secretion and a possible chemotactic relationship between these proteins and the mononuclear cells in neonatal milk. PMID- 2322610 TI - Total body water measurement in normal and diabetic pregnancy: evidence for maternal and amniotic fluid equilibrium. AB - The H2[18O] tracer dilution method was applied to quantify total body water in 6 normal nonpregnant women, 8 normal pregnant women (gestation 29.3 +/- 6.0 weeks, range 21-37 weeks), and 8 insulin-dependent diabetic pregnant subjects (gestation 29.4 +/- 6.1 weeks, range 20-37 weeks). Plateau or equilibrium enrichment of 18O in the breath CO2 was achieved at approximately 2 h in nonpregnant normal subjects. In contrast, in pregnant subjects equilibrium plateau was reached later, at approximately 3 h. In order to examine whether the amniotic fluid/fetal compartment had also reached equilibrium with the maternal water compartment, amniotic fluid samples were obtained from 5 women undergoing elective cesarean section, approximately 5 h after the administration of tracer H2[18O]. The 18O enrichment of amniotic fluid was similar to that of the mother. Total body water was similar in normal and diabetic pregnant subjects (40.4 +/- 4.4 vs. 40.1 +/- 5.8 kg) and represented 55.8 +/- 5.4 and 58.7 +/- 5.5% of body weight, respectively. These data demonstrate the usefulness of the H2[18O] tracer method to measure total body water in pregnancy and emphasize the importance of an adequate equilibrium period 4-5 h in order to measure the dilution of administered tracer. The measurements by H2[18O] tracer are similar to those previously reported with deuterium oxide. Insofar as total body water reflects lean body mass, the data suggest that body compositional changes in normal and diabetic pregnancy are qualitatively similar. PMID- 2322611 TI - Inorganic sulfate metabolism in the very low birthweight infant. AB - The effect of vitamin D supplementation on inorganic sulfate metabolism was examined in very low birth weight (less than 1,500 g) infants at biweekly intervals after birth until 6 weeks of postnatal age. Baseline serum sulfate concentrations were significantly higher in all infants (471 +/- 24 mumol/l, n = 80) than in adults (299 +/- 25 mumol/l, n = 17). In controls, the levels did not change significantly over the ensuing 6 weeks, although serum creatinine declined. Urinary sulfate excretion rose significantly to near adult levels by 2 weeks. Both urine and serum sulfate were correlated with weight gain but not with estimated glomerular filtration rate, suggesting that factors other than renal clearance have a preponderant influence on serum sulfate in these infants. At 6 weeks, the mean serum sulfate in the high-dose group (receiving 2,170 +/- 23 U/day of vitamin D, n = 41) was significantly higher than in controls (receiving 360 +/- 22 U/day, n = 40). In all infants, there was a significant correlation (r = 0.36, p less than 0.001) between serum sulfate and 25(OH)-vitamin D concentrations, but not other analytes or clinical variables, suggesting that vitamin D may be one of the factors modulating sulfate metabolism in the newborn period. PMID- 2322612 TI - Altered maternal thyroid function: fetal and neonatal myocardial metabolism. AB - The influence of the maternal thyroid status on the fetal and neonatal myocardial protein, carbohydrate and lipid metabolism was studied in rats. The neonates born of hypothyroid mothers could not survive beyond 8 days after birth. The offsprings born of hypothyroid mothers showed growth retardation, decreased level of heart mitochondrial protein, reduced myocardial free fatty acid (FFA) oxidation at birth and afterwards, low glucose oxidation by the heart at later fetal stages, and afterwards, despite low heart glycogen reserve, glucose oxidation was high. The offsprings born of hyperthyroid mothers showed stimulation in overall growth, increased myocardial FFA oxidation and increased 14C-glucose incorporation into glycogen as well as increased myocardial glucose oxidation during fetal stages. Results indicate that maternal thyroid hormones play an important role in the metabolic control of fetuses and neonates. PMID- 2322613 TI - Effects of changes in oxygen tension on lipoxygenase metabolites. Serum 15-HETE is increased in kittens exposed to hyperoxia. AB - The chronic phase of O2-induced retinopathy is characterized by retinal neovascularization. We have previously demonstrated that 15-hydroxy-5,8,11,13 eicosatetraenoic acid (15-HETE), a product of white cells, is proangiogenic. In this study, kittens exposed to in vivo hyperoxia produced increased amounts of 15 HETE. Nine litters of 30 kittens (aged 6-8 days) were used. Control kittens were left in room air; hyperoxic kittens were placed in 80% oxygen for 48 h; recovery kittens were returned to room air for 24 h following hyperoxic exposure. Following treatments, the animals were sacrified, and blood was evaluated for 15 HETE. Stimulated serum 15-HETE levels were assayed by high-performance liquid chromatography and GC-selected ion monitoring. While controls produced 0.48 +/- 0.16 (SE) nmol/ml of 15-HETE, values in the hyperoxic and recovery animals were increased at 0.7 +/0 0.2 and 0.68 +/- 0.15 nmol/ml (p less than 0.05 and p = 0.05, respectively). Increased production of this proangiogenic metabolite by WBCs (which can migrate out of blood vessels to set up extravascular angiogenic foci) may play a role in the genesis of the neovascularization process that occurs in response to oxygen-induced injury. PMID- 2322614 TI - Epidermal growth factor administered in pregnancy has little effect on placental, fetal and postnatal growth and development in rats. AB - Biosynthetic human epidermal growth factor (EGF) was injected daily into female rats (40 micrograms/rat/day) on days 14-20 of pregnancy in two experiments. Number in litter was significantly greater in EGF- than in vehicle-treated mothers in experiment 1 but not experiment 2. Number in litter affected fetal weight. When this factor was taken into account statistically, there was no significant effect of EGF treatment on fetal weight or placental weight, DNA and protein concentrations at 21 days of gestation; nor was birth weight affected by treatment. However, growth in body weight postnatally from 4 to 115 days was slightly but significantly depressed in the offspring of the EGF-treated mothers. A negative effect of additional EGF in pregnancy on subsequent milk production is postulated. The timing of attainment of developmental milestones in the offspring was not affected. PMID- 2322615 TI - Steroids and the Controlled Substances Act. PMID- 2322616 TI - Alterations in the circadian rest-activity rhythm in aging and Alzheimer's disease. AB - The suprachiasmatic nucleus, considered to be the endogenous circadian clock in the mammalian brain, shows morphological changes with aging, which become even more pronounced in Alzheimer's disease (AD). In order to assess possible functional implications of these alterations, circadian rest-activity rhythms of 6 young and 13 old volunteers and of 12 AD patients were studied with a recently developed ambulatory rest-activity monitor (RA24). Young and old volunteers showed no differences in their rest-activity rhythm in any of the variables studied. Comparison of old controls versus AD patients revealed that (1) rest activity rhythm was markedly disturbed in many of the AD patients and tended to be correlated with the severity of the dementia; (2) disturbances were most pronounced in subjects using sedating drugs; (3) disturbances in the latter group did not result from medication as no differences were found in the rest-activity patterns before and after administration of sedating drugs; (4) negative findings reported in the literature concerning circadian disturbances in AD may well have resulted from selection criteria that excluded the group of patients with the most severely affected rest-activity rhythm; and (5) rest-activity monitors offer a practical and fruitful approach for the study of circadian rhythms in humans. PMID- 2322617 TI - Molecular forms of acetylcholinesterase in subcortical areas of normal and Alzheimer disease brain. AB - We have previously reported that the 10s molecular form (G4) of acetylcholinesterase (AChE) is selectively lost from several cortical areas of Alzheimer's disease (AD) brain. In the current follow-up study, we microdissected several areas of nondemented and AD brain, including the hippocampus, amygdala, and cingulate gyrus. Tissue homogenates were separated on sucrose density gradients and the resulting fractions were analyzed for AChE activity in order to define the ratios of the predominant AChE molecular forms (G4/G1). Both the hippocampus and amygdala exhibited distinct patterns of alterations in the G4/G1 ratio which correlate with the known distribution of histopathological changes in AD brain. In order to further define the major pool of AChE that is depleted in AD, we separated fractionated tissue homogenates into salt-soluble and detergent soluble fractions. The G4/G1 ratios were only altered in the detergent-soluble fractions, indicating that the loss of the G4 AChE molecular form involves a selective depletion of the membrane pool. Available evidence would suggest that this form is the AChE molecular form physiologically relevant at the cholinergic synapse. PMID- 2322618 TI - Plasma dexamethasone levels in children given the dexamethasone suppression test. AB - To determine whether children who demonstrate dexamethasone suppression test (DST) nonsuppression have lower plasma dexamethasone levels than DST suppressors, we administered the DST to 73 patients ranging in age from 5-14 years. Plasma dexamethasone levels and postdexamethasone cortisol levels were measured at 4:00 PM on day 2. We found: (1) DST nonsuppressors had significantly lower plasma dexamethasone levels (p less than 0.03) than suppressors; similar trends were observed when the population was divided into depressed and nondepressed patients; (2) mg/m2 dose of dexamethasone was directly correlated with plasma dexamethasone (p less than 0.003) and inversely correlated with postdexamethasone plasma cortisol levels (p less than 0.04); and (3) a statistically significant inverse correlation between plasma dexamethasone levels and postdexamethasone cortisol levels (p less than 0.04). Our findings show that plasma dexamethasone levels are important in evaluating DST results in psychiatrically disturbed children and suggest that dexamethasone dosage for use in the DST in children might be better calculated in terms of body surface area. PMID- 2322619 TI - The relationships between the cortisol responses to dexamethasone and to L-5-HTP, and the availability of L-tryptophan in depressed females. AB - In order to investigate the relationships between the hypothalamic-pituitary adrenal (HPA)-axis activity, the central serotonergic neurotransmission, and the peripheral metabolism of l-tryptophan (L-TRP), the authors measured the following: the postdexamethasone cortisol values, the cortisol responses to 125 mg 5-hydroxy-L-tryptophan (L-5-HTP) orally, and the total L-TRP/competing amino acids (CAA) ratio in 64 depressed females. Severely depressed females showed significantly lower values for L-TRP/CAA, significantly higher postdexamethasone cortisol values, and cortisol responses to L-5-HTP as compared with minor depressives. Dexamethasone nonsuppressors showed significantly lower L-TRP/CAA values as compared with suppressors. The cortisol responses to dexamethasone were significantly and negatively correlated with the availability of L-TRP. The cortisol responses to L-5-HTP were not related to either the availability of L TRP or to the postdexamethasone cortisol values. PMID- 2322620 TI - Serial dexamethasone suppression test in psychiatric inpatients. AB - A sample of 100 consecutively admitted cases were recruited to test the hypothesis that an abnormal dexamethasone suppression test (AbDST) is associated with decreasing clinical severity during the course of hospitalization in various diagnostic categories. Serial DSTs and psychopathological ratings were done at the end of the first and the third week postadmission, and 1 week before discharge. DST was also done at 1-year follow-up after discharge. The results of this study strongly suggest that a dual mechanism is responsible for the prevalence of AbDST. One is related to the global psychopathology of a nonspecific quantitative mechanism in various diagnostic categories. The other is a specific qualitative mechanism relating to the depressive state, as reflected in the higher prevalence of AbDST and more consistent AbDST results across different study time points in melancholia, and also in higher AbDST rates in disorders with higher depressive scores. PMID- 2322621 TI - Plasma GABA-like activity in response to ethanol challenge in men at high risk for alcoholism. AB - Sons of alcoholic fathers (high risk, HR) and matched control men from families without alcoholism (low risk, LR) were administered, in a randomized double-blind fashion, either a placebo beverage or an isovolemic beverage containing ethanol (0.8 g/kg). Serial blood sampling for determination of plasma gamma-aminobutyric acid (GABA)-like activity, mood, and intoxication ratings were performed. The HR subjects were found to have significantly less plasma GABA-like activity than LR during the placebo condition. The alcoholic beverage condition washed out the differences in plasma GABA between groups. Significant interactions between risk group status and beverage conditions were found with respect to plasma GABA-like activity. Alcohol produced an increase in mean GABA-like activities among HR subjects, whereas a slight decline was noted among LR subjects. Plasma GABA-like activity also had a significant inverse correlation with self-reports of perceived tension in the placebo condition, and tension, confusion, and intoxication in response to the alcoholic drink. Since previous investigators have reported reduced plasma GABA levels in alcoholic individuals, reduced plasma GABA-like activity may be a biological marker for vulnerability to alcoholism or for heightened tension as a behavioral factor that predisposes to alcoholism. PMID- 2322622 TI - Plasma MHPG and age in detoxified alcoholics. AB - Plasma levels of 3 methoxy, 4-hydroxy phenylethyl glycol (MHPG) of detoxified alcoholics were found to be positively correlated with age as previously found with normal subjects. The slope of the regression line of plasma MHPG and age of the alcoholics in remission was significantly steeper than that of normal controls, indicating a faster age-related increase of MHPG in alcoholics. PMID- 2322623 TI - EEG fast frequency activity in the sons of alcoholics. AB - The EEGs of young (21-25-year-old) sons of alcoholics and their matched controls (n = 24 pairs) were computer evaluated to assess activity in the 12-20 Hz (beta) range. Subjects were blindly exposed to ethanol and placebo drinks while EEG was gathered at baseline and 90 min postconsumption. Men with alcoholic fathers [family history positive (FHP)] displayed significantly more beta activity at 90 min postethanol consumption than the men who had no alcoholic relatives [family history negative (FHN)]. In addition, when subjects were sorted into "low" and "moderate" drinkers depending on their drinking practices, additional differences were found between groups. Within the FHN subjects, moderate drinkers were found to have significantly more energy in the beta frequencies at both baseline and at 90 min postdrug than low drinkers. However, though family history positive subjects had overall increases in 12-20 Hz activity compared with the FHN subjects, no significant differences were found between moderate and low drinkers within the FHP population. Taken together, these studies suggest that drinking practices and a familial history for alcoholism can modify the beta content of the EEG in the 12-20 Hz range in young men. PMID- 2322624 TI - Failure to find interference between anti-HLA antibodies and chlorpromazine. AB - Chlorpromazine has been reported to interfere with the action of alloantibodies directed against HLA-A1. We attempted to replicate this finding using peripheral blood lymphocytes from 3 healthy donors in a complement-mediated lymphocytotoxicity assay. We were unable to find evidence of interference between chlorpromazine and the anti-HLA sera tested. Possible reasons for the difference between our finding and the previous report, as well as the implications for schizophrenia, are discussed. PMID- 2322625 TI - The sleep of dysthymic patients: a comparison with normal controls. AB - All-night electroencephalographic (EEG) sleep recordings were compared in dysthymic patients and normal controls. Patients were selected according to DSM III and underwent 2 weeks of treatment with placebo before the sleep evaluation, which also included self-assessments of sleep quality. As compared with normals, dysthymic patients demonstrated fragmented and superficial sleep with no changes in rapid eye movement (REM) sleep. In addition to sleep continuity disturbances, dysthymics had a higher percentage of stage 1 and a reduction of slow wave sleep (SWS), mainly due to a diminished percentage of stage 4. Other differences were related to a higher incidence of some EEG events, and it is suggested that the analysis of sleep microstructure is a useful approach to study sleep physiology in psychiatric patients. The classification of minor forms of depression is a controversial issue and therefore the nosological implications of our findings are discussed. PMID- 2322626 TI - A schizophrenic syndrome associated with a midbrain tegmental lesion. PMID- 2322627 TI - HLA antigens in depression and hypersomnia. PMID- 2322628 TI - Lower-bandpass filter frequency in P3 experiments: a possible cause for divergent results in schizophrenia research. PMID- 2322629 TI - Panic attacks and multiple sclerosis. PMID- 2322630 TI - Dexamethasone suppression test in Brazil. PMID- 2322631 TI - Antiseptal autoantibodies in schizophrenia. PMID- 2322632 TI - Basal ganglia calcification in schizophrenia. PMID- 2322633 TI - A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium. AB - A single and multiple oral dose administration study of meclofenamate sodium (Meclomen) was conducted in ten healthy male volunteers. An initial 300 mg oral dose on day 1 was followed by a 100 mg every 8 h dosage regimen on study days 4 through 18. Intensive plasma and urine sample collection was carried out over the first three study days, and for 120 h following administration of the final dose on day 18. Plasma and urine specimens were analyzed by a specific HPLC assay for unconjugated meclofenamic acid and metabolites I and II of meclofenamic acid before and after sample incubation with beta-glucuronidase. Meclofenamic acid was rapidly absorbed following oral dose administration. Concentrations of meclofenamic acid existed primarily as unconjugated drug in plasma, with only a small amount present in the conjugated form. Meclofenamic acid was rapidly eliminated, with an elimination half-life of approximately 1.3 h. This resulted in no detectable accumulation upon multiple dose administration. Metabolite I, which is one-fifth as active as meclofenamic acid in in vitro inhibition of cyclooxygenase, was present in unconjugated form at steady state in concentrations approximately 50 per cent of those of meclofenamic acid, as unconjugated drug. The majority of metabolite I in plasma existed as glucuronide conjugate. Metabolite II, which is inactive, was present in very significant concentrations in unconjugated form. Plasma protein binding determinations conducted on meclofenamic acid and metabolite I indicated that the free fraction of metabolite I was 8.7 to 10.9 times higher than that of meclofenamic acid. When the lower activity and lower steady state concentrations, but higher free fraction, are considered, it would appear that metabolite I may contribute significantly to the in vivo inhibition of cyclooxygenase activity seen after administration of meclofenamic acid. PMID- 2322634 TI - Effect of dietary fat content on the bioavailability of a sustained release quinidine gluconate tablet. AB - Quinidine gluconate 324 mg sustained release tablets (Quinaglute) was administered as a single dose to 15 healthy male subjects following an overnight fast, immediately following a high fat (HF) breakfast or immediately following a low fat (LF) breakfast. Serum samples were obtained over a 48 h period and analyzed for quinidine content using a high performance liquid chromatographic assay. Under the conditions of the study, both the rate and extent of quinidine bioavailability was significantly affected by food. The extent of bioavailability was statistically significantly greater (p less than 0.05) following both the HF and LF meals as compared to that in the fasted state. Rate of bioavailability was significantly enhanced following the LF meal as compared to that of the other two treatment groups. Although peak concentrations were greater and time to peak concentrations somewhat later following the HF meal versus those under fasting conditions, these differences were not statistically significant. In addition, the characteristics of the serum concentration-time profile (as defined by the number, magnitude, and time of occurrence of the multiple absorption maxima) was unique for each of the three treatment groups. Possible mechanisms underlying these results are explored. PMID- 2322635 TI - Absence of effect of food on alprazolam absorption from sustained release tablets. AB - This study examined the effect of food on alprazolam absorption from a mixed polymeric matrix sustained release (SR) tablet in 21 healthy adults. Each subject received each of three treatments according to a crossover design: 1 mg alprazolam SR tablet while fasting; 1 mg alprazolam SR tablet immediately after a standardized breakfast; 1 mg alprazolam conventional tablet while fasting. The breakfast contained approximately 33 g protein, 55 g fat, and 58 g carbohydrate (850 calories). Serial blood samples were obtained and plasma alprazolam levels determined by HPLC. Results indicate that the SR tablet was minimally affected by food. Relative bioavailabilities of the SR tablet while fasting and with food were 100 per cent and 97 per cent, respectively. Although statistically significant, differences in mean Cmax values between SR tablets administered with and without food were small (12 per cent increase with food). Rates of absorption as measured by mean tmax values were also nearly the same: 7.2 h while fasting and 7.0 h with food. Absorption was relatively uniform with the SR tablets. Coefficients of variation for Cmax, tmax, and AUC were somewhat smaller with the SR tablet than with the conventional tablet. PMID- 2322637 TI - A computer simulation of the food effect: transient changes in hepatic blood flow and Michaelis-Menten parameters as mediators of hepatic first pass metabolism and bioavailability of propranolol. AB - A physiological model of propranolol disposition was designed to help explain the large increase in AUC seen when the drug is administered with food. The mass balance equation for the liver compartment used Michaelis-Menten terms to describe hepatic metabolism. Previously published pharmacokinetic and physiological parameters were used throughout. The three parameters, Qh, Kmt, and Vmax, were varied for different durations and by a factor of two to increase AUC. The parameter variations were patterned after the changes in splanchnic blood flow following a high protein meal. The model exhibits saturation kinetics for most of the absorption phase after a simulated single oral dose of 1 mg kg-1, during which hepatic extraction is decreased. As the dose is decreased, the degree of saturation lessens. Using an input rate representative of regular release, changes to Qh caused little change in AUC. While the model was moderately sensitive to Kmt changes, large increases in AUC were seen after Vmax was altered. The sensitivity of the system to Kmt and Vmax changes became greater as the duration of the changes was increased. The AUC was most sensitive to Vmax variation, leading to the conclusion that mechanisms involving this parameter should be explored further. Reducing the input rate to mimic sustained release decreased the AUC for a given dose as well as the sensitivity of AUC to changes in Kmt and Vmax. PMID- 2322636 TI - Simulation of the hepatic metabolism of stilbene and its tricyclic derivatives by Fenton and Ruff reagents: models for cytochrome P-450 activation of chemical carcinogens. AB - Reactions of trans-stilbene, cis-stilbene, 5H-dibenzo [a,d] cyclo-heptene 5-one and 5H-dibenz [b,f] azepine (iminostilbene) with Fenton reagent [Fe (II)/H2O2] clearly simulate their hepatic metabolism. Expoxidation on the corresponding ethylenic linkage was found to be a common pathway of these compounds. Epoxides of trans-stilbene, cis-stilbene, and 5H-dibenzo[a,d]cycloheptene 5-one were further oxidized to dihydrodiols, alpha-hydroxyketones, diketones, and finally cleavage of the ethylenic bonds to the formation of the corresponding aldehydes. However, the unstable epoxide of iminostilbene gave 9-acridinecarbaldehyde that is further oxidized to 9-acridone. Reaction of both trans- and cis-stilbene with Ruff reagent [Fe III)/H2O2] gave the same oxidative products to that obtained from Fenton reagent. The radical scavenger 2,6 bis (1,1-dimethylethyl)-4-methyl phenol (BHT) decreases the total yield conversion and increases the formation ratio of both cis-epoxide and d,l-hydrobenzoin from cis-stilbene. PMID- 2322638 TI - Bioequivalence of two pharmaceutical forms of diltiazem. AB - Diltiazem, a calcium-channel blocking agent, has been shown to be a potent coronary vasodilator used in the treatment of ischaemic heart disease. The present study was conducted to compare the bioavailability of regular 60 mg tablets administered every 6 h with sustained release capsules of 120 mg administered every 12 h. High-performance liquid chromatographic analysis was carried out for determination of diltiazem and one of its metabolites desacetyldiltiazem in six male patients. The relative bioavailability of this sustained-release pharmaceutical form did not show any significant difference with that of tablets. PMID- 2322639 TI - Absolute bioavailability of terbutaline from a CR-granulate in asthmatic children. AB - The study aimed at finding the absolute bioavailability of terbutaline of a newly developed CR-granulate. Eight asthmatic children, aged 8-13 years, were given 3 mg of terbutaline as the CR-granulate, concomitant with the intravenous administration of 0.100 mg of deuterium-labelled terbutaline. The labelling of the intravenous dose made possible a separation, in the analytical step, of terbutaline originating from the intravenous and oral administration. Maximal plasma concentration, 8.7 (range: 4.9-15.2) nmol l-1, was reached after 4.7 (2.2 6.0) h. Absolute bioavailability was 10.8 (7.63-16.4) per cent. The parameter values were similar to those found after administration of terbutaline CR-tablets to adults. The CR-formulation is easily swallowed and can be dosed twice daily. Thus it should be a good alternative to elixir or plain tablets, dosed three times a day. PMID- 2322640 TI - Molecular associative memory. AB - An example of a kinetic system with address-bearing molecules and directed interactions is investigated. We show that by introducing exchange between Ising spins via the address-bearing messengers, the Hopfield model of associative memory can be made local. PMID- 2322641 TI - Molecular networks as a sub-neural factor of neural networks. AB - We describe a new approach in the research of neural networks. This research is based on molecular networks in the neuron. If we use molecular networks as a sub neuron factor of neural networks, it is a more realistic approach than today's concepts in this new computer technology field, because the artificial neural activity profile is similar to the profile of the action potential in the natural neuron. The molecular networks approach can be used in three technologies: neurocomputer, neurochip and molecular chip. This means that molecular networks open new fields of science and engineering called molecular-like machines and molecular machines. PMID- 2322642 TI - Quantized cell cycle times: interaction between a relaxation oscillator and ultradian clock pulses. AB - Control of the timing of cell division is considered to result from a relaxation cell cycle oscillator: this has one slow and one rapid component and obeys a system of two ordinary differential equations. Interactions of the slow component with an ultradian oscillator leads to quantization of cell cycle times when the free parameters of the cell cycle oscillator are chosen close to its bifurcation point. This model fits the experimental results previously reported. PMID- 2322643 TI - The global average DNA base composition of coding regions may be determined by the electron-ion interaction potential. AB - It is shown how one can understand the frequencies of occurrence of nucleotides in coding DNA sequences on the basis of electron-ion interaction potential. PMID- 2322644 TI - Pigment color patterns of molluscs as an autonomous process generated by asynchronous automata. AB - Pigment color patterns of molluscs are studied from the viewpoint of autonomy. Brownian algebra developed by Spencer-Brown (1969) is extensively used for the expression of cellular-automaton rules. When asynchronous updating is introduced for the transition of cellular automata, various kinds of patterns such as traveling waves, kinks, oscillatory local patterns etc. are generated from the same transitional rule. The type of patterns depends more sensitively on the asynchronous updating relationship rather than the transitional rule itself. Therefore, pattern changes in ontogeny can be explained without any changes in transitional rules or reaction processes. It is proposed that asynchronousness is intrinsic to living systems and that recognition of the intrinsic time is essential in understanding living systems. PMID- 2322645 TI - Effects of solar radiation on photoorientation, motility and pigmentation in a freshwater Peridinium. AB - Solar radiation has a pronounced effect on photoorientation, motility and pigmentation in the freshwater dinoflagellate, Peridinium gatunense. Photoorientation (positive phototaxis) is impaired even after short exposure times and is totally inhibited after about 2.5 h. The percentage of motile cells decreases after short exposure times and after 4 h most cells are immotile. Likewise, the mean velocity decreases after an initial light-induced increase (photokinesis) under solar radiation. Solar UV-B (280-320 nm) radiation seems to be the major cause for the effects, since cutting off shorter wavelength by an ozone cuvette or WG filters prolongs the tolerated exposure times. Possible UV-B targets are the photoreceptor pigments since solar radiation causes a massive bleaching of the cells within a few hours. PMID- 2322646 TI - Stability-complexity relationships within models of natural systems. AB - Drawing on the qualitative loop analysis models prepared by Lane for a Delaware Bay plankton community, we evaluated 12 systems that ranged from 14 to 18 entities (population, guild or nutrient). Our approach was to study models of extended trophic biotic communities and examine the stability-complexity issue not only as it exists between systems (the traditional approach) but also with respect to the entities and relationships within a given system. We found no statistically significant inverse relationship for stability and complexity between systems. Within a system, a significant inverse relationship at the entity level was observed embedded in an increasing stability positively related to increasing subsystem size. Also, within a system and from system to system, several entities were seen to vary their roles with respect to stability. These results extend the stability-complexity issue to models of relatively large biotic communities and raise issues concerning the roles, with respect to stability, played by entities within communities. PMID- 2322647 TI - Open systems living in a closed biosphere: a new paradox for the Gaia debate. AB - While energetically open, the biosphere is appreciably closed from the standpoint of matter exchange. Matter cycling and recycling is hence a necessary and emergent property of the global-scale system known as Gaia. But how can an aggregate of open-system life forms have evolved and persisted for billions of years within a planetary system that is largely closed to matter influx and outflow? The puzzling nature of a closed yet persistent biosphere draws our attention to the course of evolution of fundamental metabolic strategies and matter-capture techniques. It suggests a facet of the Gaia hypothesis, framed in terms of persistence. The oceans, atmosphere, soils and biota constitute a complex system which maintains and adjusts matter cycling and recycling within the constraints of planetary closure such that open-system forms of life can persist. This weaker version of the Gaia hypothesis may be useful because it readily lends itself to at least one form of test. What is the solution to the closed biosphere puzzle, and does it indicate that Gaia merits status as a discrete entity? We suggest several disciplines within the field of biology that might provide tools and perspectives toward reaching a solution. These disciplines include artificial closed ecosystems, prokaryote evolution, the nexus of thermodynamics and evolutionary biology, and hierarchy theory in ecosystem modeling and evolution theory. PMID- 2322648 TI - Does delay in diagnosis of breast cancer affect survival? AB - 1675 breast cancer patients in the Auckland regional area have been divided into two major groups according to delay in diagnosis greater or less than six weeks. Overall there is no difference in survival although the variables tumour size, skin attachment, and nipple retraction are more common in the group with longer delay, and grade III tumours in those with short delay. Three important prognostic variables (the presence of tumour steroid receptors, positive axillary nodes, and distant metastases at diagnosis) are equally distributed and have a similar effect on survival within the two delay groups. However, in a subgroup of women with negative axillary nodes, short delay is associated with poorer survival, independent of tumour size. More tumours with grade III histology and a negative progesterone receptor status are found in this subgroup. Thus, short delay may constitute a new prognostic variable of some importance when in association with negative axillary nodes. PMID- 2322649 TI - Distribution of estrogen and progesterone receptors in healthy tissue adjacent to breast lesions at various stages--immunohistochemical study of 107 cases. AB - The purpose of this study was to determine the distribution of ER+ (estrogen receptor) and PR+ (progesterone receptor) epithelial cells in normal mammary tissue or in tissue in contact with or involved in benign or malignant processes. Three important findings emerged from this study. First, a true dissociation was observed between ER+ and PR+ cells in mammary tissue. In premenopausal women some cells express only progesterone receptors. In premenopausal normal tissue, regardless of the menstrual cycle status, 6% of cells are ER+ and 29% PR+. Second, during the menstrual cycle the percentage of positive cells varies. This finding would indicate a change in cell recruitment rather than in intracellular levels. Finally, specific changes in the proportion of positive cells in normal tissue in contact with epithelial proliferations were noted. This finding suggests the possibility of either a diffusible factor or a cellular pathological process spreading beyond areas displaying morphological changes. PMID- 2322650 TI - Clinical/genetic features in hereditary breast cancer. AB - Patients from hereditary breast cancer-prone (HBC) families provide one of the most powerful and potentially cost effective models for cancer prevention and control. Paradoxically, this opportunity is often missed in the clinical practice setting due, in part, to inattention to the family history and/or lack of knowledge about breast cancer genetics. We describe the family study process, wherein documentation of genealogy, medical, and cancer history through pathology verification is attained, often on extended families. The findings of such studies are illustrated by description of nine breast cancer-prone families. These families illustrate several important clinical/genetic features such as age of cancer onset, bilaterality and/or multiple primary cancer occurrences, incomplete gene penetrance, and the identification of putative obligate gene carriers. Interpretation of HBC pedigrees is dependent upon the understanding of these issues, which in turn may enable the physician to more readily identify those individuals who might benefit from highly targeted breast cancer control measures. PMID- 2322652 TI - Haematology in HIV disease. PMID- 2322651 TI - Role of transforming growth factor-alpha-related peptides in the autocrine/paracrine control of experimental breast cancer growth in vitro by estradiol, prolactin, and progesterone. AB - We have recently suggested that estradiol (E2), prolactin (oPrl), and progesterone (Pg) support the growth of the hormone-responsive N nitrosomethylurea (NMU) rat mammary tumor in soft agar through autocrine/paracrine mechanisms. To gain insight into the nature of these hormonally regulated growth factors, we tested the ability of two monoclonal antibodies (MAb-425 and 528) directed against the epidermal growth factor receptor (EGF-R) to inhibit the colony-stimulating effects of conditioned media (CM) obtained from E2, oPrl, and Pg-treated NMU rat mammary tumors. Since both MAbs are specific for human EGF-R, MCF-7 breast cancer cells grown in soft agar in the absence of serum were used as our indicator system. Both MAb-425 and 528 totally abolished the colony-stimulating effect of genuine EGF, while having no agonistic/antagonistic action when added alone. Both MAb-425 and 528 markedly inhibited the colony-stimulating effect of rat mammary tumor E2-CM in a dose dependent fashion. MAb-425 was also found to inhibit the growth-promoting action of Pg-CM, although this effect appeared to be somewhat less consistent and pronounced than that observed with E2-CM. In contrast, the colony-stimulating effect of Prl-CM was only rarely and, usually, modestly affected by the addition of either MAb-425 or 528. Our data suggest that in the NMU mammary tumor grown in soft agar, EGF/TGF alpha-related peptides are produced upon exposure to E2 and possibly Pg but only rarely following Prl administration. The possible role of these growth factors as mediators of hormonal effects in our experimental system remains to be established. PMID- 2322653 TI - Cancer recurrence as a traumatic event. AB - The authors hypothesized that cancer recurrence can be understood and therefore treated as a traumatic event that places patients at risk for stress response symptoms. To test this, they gave 40 patients with recurrent malignancies of mixed sites the Impact of Event Scale (a measure of response to specific stressors), the Psychosocial Adjustment to Illness Scale-Self-Report version (a measure of general adjustment to illness), and a semi-structured interview in which the patients were asked about their reactions to and experiences surrounding the recurrence, compared with those surrounding their initial diagnosis. In self-report measures and in the interview, patients clearly perceived that adjustment to recurrence is more problematic than adjustment to initial diagnosis. The findings were consistent with an expectation derived from the stress-disorder literature: patients who reported having been completely surprised by the recurrence and those undergoing their first recurrence showed significantly more intrusive and avoidant stress response symptoms. Given the heterogeneity of the patient population and the relatively limited sample size, further study is needed to assess the contribution of other important mediating factors in the development of stress disorders. Because the predictors in this study (extent of surprise and number of previous recurrences) can be identified before or immediately following a recurrence, primary and secondary interventions might help prevent stress disorders in patients who may have had unrealistic expectations. PMID- 2322654 TI - Headache versus nonheadache state: a study of electrophysiological and affective changes during muscle contraction headaches. AB - Seventeen carefully screened muscle contraction headache sufferers were tested in both the headache and the nonheadache state. At baseline, forehead and trapezius EMG were higher, whereas finger temperature and finger blood volume were lower in the headache than the nonheadache state. At a borderline level, physiological reactivity was greater during the headache than the nonheadache state in response to a reaction-time stressor. During the headache state, subjects also reported themselves to be more anxious, depressed, and angry than they were in the nonheadache state and said they felt themselves to be more hassled by external stressors and less able to cope with, prevent, and control their headaches. The findings are consistent with the notion that shoulder/neck tension and emotional arousal contribute to tension headaches. Evidence is less clear for the contribution of vasomotor factors and general physiological reactivity. PMID- 2322655 TI - Fall-off in reporting life events: effects of life change, desirability, and anticipation. AB - The influence of event characteristics on recall was examined by directly comparing fall-off in reporting life events as a function of life change, desirability, and anticipation. We collected information from a sample of 1,669 blue-collar workers on stressful life events that occurred in a 1-year interval before the questionnaire was administered. The results indicated no fall-off in reporting events associated with marked life changes (ie, salient events). In contrast, significant fall-off was observed for events characterized by varying degrees of desirability and anticipation. Although ratings of desirability and saliency were not independent, saliency of life events emerged as the dimension most closely associated with accuracy of event reporting. Research on the reliability of measures of life events and the association between event characteristics and illness should consider the kinds of systematic reporting differences observed here. PMID- 2322656 TI - Emphasis on behavioral sciences increasing at the World Health Organization. PMID- 2322657 TI - The relationship between psychosocial factors and breast cancer: some unexpected results. AB - A growing body of research suggests a link between psychosocial factors and breast cancer. Research in this area often contains methodological problems, however, such as small sample size, inadequate comparison groups, omission of important control variables, inclusion of only a few psychosocial variables, and failure to analyze moderating effects. To overcome these problems, the present study examined the link between breast cancer and multiple psychosocial variables (life events, coping, Type A behavior pattern, availability of social support) among 1,052 women with and without breast cancer. After controlling for history of breast cancer and age, we found very few significant relationships between psychosocial variables and breast cancer. Furthermore, the relationship between life events and breast cancer was not moderated by coping, Type A, or availability of social support. Methodological and substantive reasons for these findings are discussed. PMID- 2322658 TI - Effects of the environmental pollutants on heme oxygenase activity and cytochrome P-450 content in fish. PMID- 2322659 TI - Estuarine sediment bioassay with oyster pediveliger larvae (Crassostrea gigas). PMID- 2322660 TI - Use of carbonyl iron to induce iron loading in the mussel Mytilus edulis. PMID- 2322661 TI - Toxicity of fenitrothion degradation products to medaka (Oryzias latipes). PMID- 2322662 TI - Effect of thiol compounds and flavins on mercury and organomercurial degrading enzymes in mercury resistant aquatic bacteria. PMID- 2322663 TI - Monocrotophos: short-term toxicity in rats. PMID- 2322664 TI - Comparison of dislodgable and total residues of three pyrethroids applied to cotton in Arizona. PMID- 2322665 TI - Naphthalenes associated with treated wastewater effluents in an urban national wildlife refuge. PMID- 2322666 TI - Application of the Microtox system to assess the toxicity of pesticides and their hydrolysis metabolites. PMID- 2322667 TI - Effects of diuron and fluometuron metabolites on the growth and fiber quality of cotton (Gossypium hirsutum). PMID- 2322668 TI - Biochemical diagnosis of occupational exposure to lead toxicity. PMID- 2322669 TI - Air pollution effects on the leaf structure of Laurus nobilis, an injury resistant species. PMID- 2322670 TI - Chloroperoxidase mediated halogenation of phenols. PMID- 2322671 TI - Simultaneous determination of triphenyltin and its metabolites, mono- and diphenyltin, in biological materials by capillary gas chromatography. PMID- 2322672 TI - Use of lichen biomass to monitor dissolved metals in natural waters. PMID- 2322673 TI - Levels of metals in canned meat products: intermetallic correlations. PMID- 2322674 TI - Levels of toxic mineral elements in selected foods marketed in Nigeria. PMID- 2322675 TI - Clinical, chemical, and hematological parameters in cattle kept in a cadmium contaminated area. PMID- 2322676 TI - Urinary selenium levels in Japanese males and females. PMID- 2322677 TI - Radioactive hazard of potable water in Virginia and Maryland. PMID- 2322678 TI - Personal diffusive sampler for methanol, a hydrophilic solvent. PMID- 2322679 TI - Performance of a new ecotoxicological index to assess environmental impacts on freshwater communities. PMID- 2322680 TI - Distribution and transport kinetics of radionuclides 99Mo and 131I in a simulated aquatic ecosystem. PMID- 2322681 TI - Biodegradation of azo dyes in multistage rotating biological contactor immobilized by assimilating bacteria. PMID- 2322682 TI - Determination of melamine and three hydrolytic products by liquid chromatography. PMID- 2322683 TI - Changes in poultry litter toxicity with time. PMID- 2322684 TI - Lack of an effect of soman on norepinephrine-induced relaxations of porcine coronary arteries. PMID- 2322685 TI - Primary toxicity of bromadiolone on the coypu. PMID- 2322686 TI - Acute oral toxicity of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether. PMID- 2322687 TI - Effect of reticuloendothelial system blockade on the biotransformation of methyl mercury in the rat. PMID- 2322688 TI - Effect of mercury on glutathione and thyroid hormones. PMID- 2322689 TI - Accumulation, metabolism and toxicity of parathion in tadpoles. PMID- 2322690 TI - Effect of chemically contaminated marine sediment on naupliar production of the marine harpacticoid copepod, Tigriopus californicus. PMID- 2322691 TI - Profile of metal-binding proteins and heme oxygenase in red carp treated with heavy metals, pesticides and surfactants. PMID- 2322692 TI - Acute lethal toxicity of ammonia and suspended sediment mixtures to chinook salmon (Oncorhynchus tshawytscha). PMID- 2322693 TI - Effects of clomiphene and tamoxifen in vivo on the bone-resorbing effects of parathyroid hormone and of high oral doses of calcitriol (1,25(OH)2D3) in rats with intact ovarian function consuming low calcium diet. AB - Two experiments were undertaken to study the abilities of clomiphene citrate (20 mg/kg body wt/wk s.c.) and tamoxifen citrate (20 mg/kg body wt/wk s.c.) to slow bone resorption mediated by (a) endogenous parathyroid hormone (PTH) and (b) exogenous calcitriol (1,25(OH)2D3) in vivo in rats with intact ovarian function. Groups of rats with 45Ca-labelled bones were fed a low-calcium (0.01% Ca) diet to stimulate secretion of PTH. Neither clomiphene nor tamoxifen showed the mobilization of 45Ca from femoral bone or prevented the reduction in bone calcium induced by feeding this diet. Moreover these drugs did not depress the urinary excretion of 45Ca or hydroxyproline. These observations indicated that clomiphene and tamoxifen did not inhibit PTH-mediated bone resorption. Administering calcitriol (50 ng/day) orally for 14 days raised plasma calcium, increased urinary 45Ca and its specific activity and decreased femur 45Ca: all these responses were similar in animals receiving calcitriol alone and calcitriol with clomiphene or tamoxifen. The femur 45Ca values (dpm X 10(-3) were: (mean +/- SD, n = 8) placebo, 1901 +/- 127; 1,25(OH)2D3, 1727 +/- 96**; clomiphene + 1,25(OH)2D3, 1694 +/- 93**; tamoxifen + 1,25(OH)2D3, 1664 +/- 61**. (** = P less than 0.01). Thus neither clomiphene nor tamoxifen prevented calcitriol-mediated bone resorption in vivo in the rat. PMID- 2322694 TI - A study of complaints and their relation to vertebral destruction in patients with osteoporosis. AB - Patients with spinal osteoporosis suffer from vertebral deformation, loss of height and back pain, as well as from functional limitations and alterations of mood. So far little is known about the extent of these clinical symptoms at all and whether they are related in a predictable manner to the fractures or damages of bone structure. In the present study we investigated the relation between vertebral deformation and clinical symptoms in 70 patients with osteoporosis. Clinical data like pain, functional limitations and parameters of mood were examined by a standardized questionnaire. The numbers of vertebral fractures were determined, and the vertebral destruction was quantified using the Spine Deformity Index (SDI). The symptoms and functional limitations were graded and correlated to the SDI and the number of fractures. Our results underline a relation between the extent of vertebral deformation and the reduction in quality of life by pain, functional limitations and alterations of mood. This relationship was absent or less evident, if the number of fractures was taken into account. Besides the difficulties concerning the grading and quantification of clinical symptoms and outcome of disease, our study revealed that there is a causal relation between the extent of vertebral destruction measured by the SDI and the extent of these clinical parameters. PMID- 2322695 TI - Treatment of multiple myeloma with nasal spray calcitonin: a histomorphometric and biochemical study. AB - To evaluate the effect of calcitonin on the bone lesions of multiple myeloma, we studied 11 patients treated for 3 months with salmon calcitonin in nasal spray (200 IU) and 500 mg of elemental calcium/day. Pre- and post-treatment biochemical and histomorphometric parameters were compared to those of 12 patients treated for the same time with 500 mg elemental calcium alone. Both groups received the same hematological treatment. In the group treated with calcitonin there was a significant increase (P less than 0.01) in trabecular bone volume, cortical thickness, osteoid volume and osteoid seam thickness index and the osteoclast resorption surface fell significantly (P less than 0.01). There was also a decline (P less than 0.001) in corrected serum calcium and OHP/Cr, which accounts for the diminished bone resorption. The group not treated with calcitonin showed only significant changes in OHP/Cr which increase (P less than 0.05). Calcitonin was perfectly tolerated by all patients and our results show it to be useful in the treatment of bone lesions of multiple myeloma. PMID- 2322696 TI - Juniors' hours of work. PMID- 2322697 TI - Global medicine on your doorstep. PMID- 2322698 TI - Social influences and cardiovascular risk factors as determinants of plasma fibrinogen concentration in a general population sample of middle aged men. AB - OBJECTIVE: To analyse the relation between fibrinogen concentration and social class and other social factors found to be related to mortality. The results regarding cardiovascular disease are unpublished, as yet. DESIGN: Cross sectional population study. SETTING: City of Gothenburg, Sweden. SUBJECTS: 639 Men from a population sample of 1016 men aged 50 in 1983. They were all employed and had no history of myocardial infarction or stroke. Fibrinogen values were available for all of them. MAIN OUTCOME MEASURE: Fibrinogen concentration in relation to socioeconomic state according to occupation, and other social influences determined as number of people in the household and scores of social activities and activities in and outside the house. RESULTS: Men with low scores for activities at home had a mean plasma fibrinogen concentration of 3.34 g/l (95% confidence interval 3.21 to 3.47), whereas those with an intermediate score had a mean concentration of 3.16 (3.00 to 3.32) g/l and those with a high score 3.02 (2.95 to 3.10) g/l. Similar inverse relations were noted for the two other activity scores and for occupational class (class 1 being unskilled and semiskilled workers and class 5 professionals and executives) and the number of people in the household. Smoking exerted a strong influence on fibrinogen concentration, the relations between fibrinogen concentration and social factors being evident only in non-smokers. The mean difference in fibrinogen value between the non-smokers with the lowest activity scores at home and those with the highest scores was 0.36 (0.19 to 0.54) g/l, and similar differences were seen for the two other activity scores. Multiple regression analyses showed smoking, body mass index, the sum of all activities (inverse relation), and diabetes to be independently associated with fibrinogen value, whereas occupational class (p = 0.81) and the number of people in the household (p = 0.09) were not. CONCLUSIONS: Psychosocial influences seem to influence the coagulation system in the body in a way that is associated with cardiovascular disease and premature death. PMID- 2322699 TI - Implications of inflammatory changes on cervical cytology. AB - OBJECTIVE: To assess premenopausal women with inflammatory changes on cervical cytology for genital infections and cervical abnormalities. DESIGN: Prospective study of women attending general practice and family planning clinics who had a recent cervical cytology result with inflammatory changes. SETTING: Department of genitourinary medicine. PATIENTS: 102 Premenopausal women with recent cytology result showing inflammatory changes and with no history of antibiotic or antifungal treatment since their smear. INVESTIGATIONS: Genital examination and microbiological screening for genital infections; colposcopic examination about six weeks later. MAIN OUTCOME MEASURES: Detection of genital infections, particularly those sexually acquired, and abnormalities on colposcopy. RESULTS: Genital infections were isolated in 77 patients, and one or more sexually acquired infections were found in 22. Prevalence of sexually acquired infections was significantly correlated with younger age (particularly being under 25), being single, separated, or divorced; using non-barrier contraception; and recent change of sexual partner. An abnormality on colposcopy was found in 36 women. There was a strong correlation of a sexually acquired infection with an abnormality at colposcopy; hence younger women were more likely to have a colposcopic abnormality. CONCLUSIONS: Inflammatory changes on cytology are often associated with the presence of a sexually acquired infection and premalignant disease of the cervix, particularly in younger, single women using non-barrier contraception. PMID- 2322700 TI - Intravenous use of slow release morphine sulphate tablets. PMID- 2322701 TI - Coffee consumption as trigger for insulin dependent diabetes mellitus in childhood. PMID- 2322702 TI - Increasing suicide rates in young adults. PMID- 2322703 TI - Contribution of a general practitioner hospital: a further study. AB - OBJECTIVE: To audit the workload of a general practitioner hospital and to compare the results with an earlier study. DESIGN: Prospective recording of discharges from the general practitioner hospital plus outpatient and casualty attendances and of all outpatient referrals and discharges from other hospitals of patients from Brecon Medical Group Practice during one year (1 June 1986-31 May 1987). SETTING: A large rural general group practice which staffs a general practitioner hospital in Brecon, mid-Wales. PATIENTS: 20,000 Patients living in the Brecon area. RESULTS: 1540 Patients were discharged from the general practitioner hospital during the study period. The hospital accounted for 78% (1242 out of 1594) of all hospital admissions of patients of the practice. There were 5835 new attendances at the casualty department and 1896 new outpatient attendances at consultant clinics at the hospital. Of all new outpatient attendances by patients of the practice, 71% (1358 out of 1896) were at clinics held at the general practitioner hospital. Since the previous study in 1971 discharges from the hospital have increased 37% (from 1125 to 1540) and new attendances at consultant clinics 30% (from 1450 to 1896). The average cost per inpatient day is lower at this hospital than at the local district general hospital (pounds 71.07 v pounds 88.06 respectively). CONCLUSIONS: The general practitioner hospital deals with a considerably larger proportion of admissions and outpatient attendances of patients in the practice than in 1971 and eases the burden on the local district general hospital at a reasonable cost. IMPLICATIONS: General practitioner hospitals should have a future role in the NHS. PMID- 2322704 TI - Appropriateness of hospital referral for hypertension. AB - OBJECTIVE: To examine the efficiency of referral to an outpatient clinic and particularly the differences between referrals from general practitioners practising in health centres and those from other general practitioners. DESIGN: Retrospective audit of referral letters and case notes by comparison with externally set standards of appropriateness of referrals over two years. SETTING: Outpatient hypertension clinic at Western Infirmary, Glasgow. PATIENTS: 306 Consecutive new referrals of patients over two years (1 May 1986 to 30 April 1988), for whom case notes were available in 298. MAIN OUTCOME MEASURES: Congruence of referrals with each of two standards of appropriateness based on published opinion on specialist referral (standard 1 was stricter than standard 2) and completeness of referral letters. RESULTS: Of the 298 referrals, those from general practitioners accounted for 205, from other hospital departments 68, and from other sources 25. Overall, 84 referrals of the 205 from general practice met the first standard and 134 met the second, more lenient standard. 58 Referral letters from outside the hospital had some item missing. Referrals from general practitioners working in health centres (a fifth of the total) were significantly more likely to meet both standards (p less than 0.01) and to send a complete referral letter (p less than 0.001) than the 145 referred by other general practitioners. CONCLUSIONS: According to the standards used, general practitioners in health centres made more appropriate referrals, and further investigation is needed to identify the underlying factors responsible. PMID- 2322705 TI - Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm. AB - Treatment with erythropoietin is highly effective and beneficial if given with care. In view of its cost, however, it is essential to exclude and treat other causes of anaemia before considering using this hormone. After treatment is started the important points for success are regular review of iron availability state combined with a slow correction of the anaemia. Failure of response requires a thorough search for a possible cause, which should be corrected before considering an increased dose of the hormone. Regular monitoring for potential complications, particularly a rise in blood pressure, is required. PMID- 2322706 TI - Winter sports injuries in a snowless year: skiing, ice skating, and tobogganing. PMID- 2322707 TI - Leishmaniasis. PMID- 2322708 TI - Leukemia and lymphoma among young people near Sellafield. PMID- 2322709 TI - Infectious complications of blood transfusion. PMID- 2322710 TI - Cancer of the oesophagus. PMID- 2322711 TI - Stone fish bite. PMID- 2322712 TI - Analysis of serial measurements in medical research. PMID- 2322713 TI - Superglue inadvertently used as eyedrops. PMID- 2322714 TI - Training in accident and emergency. PMID- 2322715 TI - Non-steroidal anti-inflammatory drugs and peptic ulcers. PMID- 2322716 TI - Cognitive impairment and early death in the elderly. PMID- 2322717 TI - High street eye tests. PMID- 2322718 TI - Medicine in Romania. PMID- 2322719 TI - Medical problems of adults who were sexually abused in childhood. AB - The aim of the study was to see whether adults who had been sexually abused in childhood were vulnerable to physical symptoms and therefore investigation and intervention. The case histories of seven patients who were aged 22-39, were under the care of three consultant psychiatrists, had experienced childhood sexual abuse, and had a history of medical or surgical intervention were surveyed. The patients had had a mean of 18 contacts with non-psychiatric consultant teams and a mean of eight operations, with a high rate (66-70%) of normal findings. They had experienced many somatic symptoms, which led to investigations and interventions in the specialties of gynaecology, obstetrics, gastroenterology, urology, rheumatology, haematology, orthopaedics, neurology, and neuropsychiatry. The history of childhood sexual abuse was recognised only in the later stages of this medical and surgical intervention. The possibility of childhood sexual abuse should be considered earlier in such cases to prevent further unnecessary intervention. PMID- 2322720 TI - Preregistration house officers in the four Thames regions: I. Survey of education and workload. AB - OBJECTIVE: To assess the education and workload of preregistration house officers in the four Thames regions. DESIGN: Postal questionnaire. SETTING: Teaching and non-teaching hospitals in the four Thames regions. PARTICIPANTS: 1064 Preregistration house officers. RESULTS: Response rate was 70% (740 replies). Nine per cent of house officers (66/729) worked a rota of one in two. The average house officer had 20.4 inpatients under his or her care and admitted 23.2 patients per week. Sixty two per cent of house officers (459/740) felt that they spent an excessive amount of time on non-medical tasks of no educational merit; 75% (546/725) had never received adequate guidance on breaking bad news and 64% (467/729) had never received adequate guidance on pain control; 34% (249/731) did not feel confident that they could perform cardiopulmonary resuscitation unsupervised. House officers would tend to recommend their post to a friend. CONCLUSIONS: There are deficiencies in preregistration training in the four Thames regions. The General Medical Council's requirements are not being heeded. PMID- 2322721 TI - Preregistration house officers in the four Thames regions: II. Comparison of education and workload in teaching and non-teaching hospitals. AB - OBJECTIVE: To detect differences in the education and workload of preregistration house officers working in teaching and non-teaching hospitals. DESIGN: A postal questionnaire. SETTING: Teaching and non-teaching hospitals in the four Thames regions. PARTICIPANTS: 1064 Preregistration house officers. RESULTS: Response rate was 61% for teaching hospitals and 73% for non-teaching hospitals. House officers in teaching hospitals had significantly fewer inpatients under their care (house physicians 16.9 v 22.9, house surgeons 17.9 v 20.3) and admitted fewer emergency patients per week (house physicians 7.7 v 12.7, house surgeons 6.5 v 9.8). More house officers in teaching hospitals reported that they had too few patients to provide adequate clinical experience. More of their time was consumed by administrative activities devoid of educational value. CONCLUSION: Preregistration house officer posts at teaching hospitals provide less clinical activity and are perceived as less educationally satisfactory by their holders than those elsewhere. PMID- 2322722 TI - Patients with private health insurance using NHS facilities in preference to private care. PMID- 2322723 TI - Comparison of oral preparations of heroin and methadone to stabilise opiate misusers as inpatients. PMID- 2322724 TI - Deaths from asthma in the mentally handicapped. PMID- 2322725 TI - Prevalence of subjective dysphagia in community residents aged over 87. PMID- 2322726 TI - Alcoholic doctors can recover. AB - A survey of doctors with alcohol and drug dependence who joined a self help group was carried out to find out whether they had recovered and whether their lifestyles and careers had been affected. After the group had been meeting for eight years 100 doctors had attended for over six months, and they were sent a questionnaire. Sustained recovery from dependence was achieved by 76 doctors for an average of nearly five and a half years. Among 15 who had not recovered, seven had died of causes directly related to alcohol misuse. Nearly a fifth of those surveyed had been assessed by the medical committee of the General Medical Council, and nearly half had lost their job but were in satisfactory employment again at the follow up survey. Those who recovered had contributed nearly 500 years of service to health care since contacting the group. PMID- 2322727 TI - Interleukin 2. PMID- 2322728 TI - Doctors and medical negligence. PMID- 2322729 TI - Food handlers and food poisoning. PMID- 2322730 TI - Absorption of irrigating fluid during transcervical resection of endometrium. PMID- 2322731 TI - Node negative breast cancer. PMID- 2322732 TI - Open access gastroscopy. PMID- 2322734 TI - Increasing hospital waiting lists. PMID- 2322733 TI - Anabolic steroids and infarction. PMID- 2322735 TI - Sectioning of patients with visual difficulties. PMID- 2322736 TI - New York doctor with AIDS settles out of court. PMID- 2322737 TI - Association between certain foods and risk of acute myocardial infarction in women. AB - STUDY OBJECTIVE: To examine the relation between selected foods and acute myocardial infarction in women. DESIGN: Case-control study conducted over five years. SETTING: 30 Hospitals with coronary care units in northern Italy. SUBJECTS: 287 Women who had had an acute myocardial infarction (median age 49, range 22-69 years) and 649 controls with acute disorders unrelated to ischaemic heart disease (median age 50, range 21-69 years) admitted to hospital during 1983 9. MAIN OUTCOME MEASURES: Frequency of consumption of various foods and odds ratios of risks associated with these foods. RESULTS: The risk of acute myocardial infarction was directly associated with frequency of consumption of meat (odds ratio 1.5 for upper v lower thirds of consumption), ham and salami (1.4), butter (2.3), total fat added to food (1.6), and coffee (2.8). Significant inverse relations were observed for fish (0.6), carrots (0.4), green vegetables (0.6), and fresh fruit (0.4). The risk was below one for moderate alcohol consumption (0.7) and above one for heavier intake (1.2). Allowance for major non dietary covariates, including years of education, smoking, hyperlipidaemia, diabetes, hypertension, and body mass index, did not appreciably alter the estimates of risk for most of the foods; for coffee, however, the odds ratio fell to 1.8 on account of its high correlation with smoking. CONCLUSIONS: The frequency of consumption of a few simple foods may provide useful indicators of the risk of myocardial infarction. Furthermore, specific foods such as fish, alcohol, or vegetables and fruits may have an independent protective role in the risk of cardiovascular diseases. PMID- 2322738 TI - Cryptosporidiosis in England and Wales: prevalence and clinical and epidemiological features. Public Health Laboratory Service Study Group. AB - In a two year study carried out by 16 public health laboratories in England and Wales 62,421 patients with presumed infective diarrhoea were investigated. Cryptosporidium infection was identified in 2% (1295), ranging from 0.5% to 3.9% among laboratories. The positivity rate for cryptosporidium was highest in 1-4 year olds, and in children cryptosporidium was the second commonest pathogen after campylobacter. Illness was usually limited to abdominal cramps and watery diarrhoea with six motions/24 hours at worst and lasting seven days. Fewer than half the patients reported fever or vomiting. More severe illness with fever, abdominal cramps, vomiting, and watery diarrhoea of frequency greater than five motions in 24 hours was reported by only a tenth of cases but with a significantly increased prevalence in young adult males. One hundred and fifty five patients (12%) probably acquired their infection abroad; 102 (9%) of patients who acquired their infection at home reported drinking raw milk in the month before onset, and 253 (22%) reported close contact with farm animals. Most laboratories experienced sudden infrequent increases in incidence in the community, only one of which was attributed to a recognised outbreak, which occurred in a nursery. Cryptosporidium should be routinely sought by laboratories investigating acute infectious diarrhoea, especially in children; up to a quarter of cases may be directly zoonotic, and the remainder may be due to person to person spread and waterborne infection. PMID- 2322739 TI - Association between parasuicide and Saint Valentine's Day. PMID- 2322740 TI - Orbital pseudotumour secondary to giant cell arteritis: an unreported condition. PMID- 2322741 TI - Injuries caused by tripping over paving stones: an unappreciated problem. PMID- 2322742 TI - Resuscitation decisions in a general hospital. PMID- 2322743 TI - A handout about tetanus immunisation: influence on immunisation rate in general practice. AB - OBJECTIVE: To assess the influence of giving patients a handout about tetanus immunisation on the rate of immunisation against tetanus among adults in a general practice. DESIGN: Monthly tetanus immunisation rates were audited before and after the handout was introduced. SETTING: A practice with six doctors and a list of 11,000 patients in an urban area of Hertfordshire. INTERVENTIONS: In the first month reception staff were instructed to give a handout about tetanus immunisation to all adults presenting at the reception desk. In the next seven months the doctors used the handouts opportunistically during consultations. RESULTS: No significant change in immunisation rate was detected in the first month in which the handouts were used. During the next seven months the median monthly rate rose threefold. CONCLUSION: Handouts given to patients can increase the uptake of preventive services in general practice. PMID- 2322744 TI - How to organise a medical symposium for general practitioners. PMID- 2322745 TI - Dangers of thrombolysis. PMID- 2322746 TI - Benefits of animal research and the doctor's responsibility. PMID- 2322747 TI - Identification of the cystic fibrosis gene. PMID- 2322748 TI - Clinical directorates. PMID- 2322749 TI - Assessment of care of children with sickle cell disease. PMID- 2322750 TI - HIV infection and tuberculosis. PMID- 2322751 TI - NSAIDs and peptic ulcers. PMID- 2322752 TI - Fibromuscular dysplasia of renal arteries and acute loin pain. PMID- 2322753 TI - The Medical Information Bus. PMID- 2322754 TI - The measurement of nonelastic work of breathing using a commercially available respiratory integrator. AB - The authors compared real-time, breath-by-breath work of breathing (WOB) measurements made with a Hewlett-Packard 8815A respiratory integrator with nonelastic WOB values obtained by planimetry of pressure-volume tracings. They measured WOB while normal subjects breathed through a low-resistane mouthpiece. The integrator-derived values for WOB correlated well with planimeter-derived values (r = 0.97). Valid measurements of nonelastic WOB can be made at the bedside in realtime using the Hewlett-Packard 8815A without the addition of custom-built circuitry or hardware. PMID- 2322756 TI - The AR-8800--a new impedance pneumograph (plethysmograph) respiratory monitor. AB - The Atlas AR-8800, an impedance pneumograph respiratory monitor, is claimed to detect both apnea and hypoventilation. The authors tested the monitor on eight anesthetized patients and found the apnea alarm to be effective and efficient. In addition, the ventilation alarm index, a system specific to this monitor, detected hypoventilation and also differentiated between irrelevant body movements and apnea. PMID- 2322755 TI - A comparison of a new reflectance oximeter with the Hewlett-Packard ear oximeter. AB - The purpose of this study was to characterize the accuracy and dynamic response characteristics of traditional transmittance pulse oximeters and a new reflectance pulse oximeter with regard to the current standard in oximetry, the Hewlett-Packard ear oximeter. Studies were performed with 15 healthy male and female subjects. A rebreathing technique was employed to produce a steady fall in oxygen saturation and to maintain constant, eucapnic, end-tidal CO2 levels. The oximeters' analog outputs were recorded by a Western Graphtec Linearecorder and by an IBM-PC utilizing an analog-to-digital converter for data collection at 5 Hz. The agreement between two clinical methods of measurement was used as the statistical technique of comparing new technology (pulse oximetry) with the current standard (Hewlett-Packard ear oximetry). The mean of the difference between the Hewlett-Packard and the pulse oximeter with reflectance sensor was 0.28%, with a range of difference of +/- 3.49%. This value was similar to that of the transmittance oximeters (Criticare 501+: 0.92 +/- 2.11), (Physio-Control: 3.15 +/- 2.04), (Ohmeda 3700: 2.05 +/- 2.06). There was virtually no response time difference between the reflectance oximeter with the sensor placed on the subject's forehead and the Hewlett-Packard ear oximeter. The authors conclude that the accuracy of the reflectance oximeter is within the limits of clinical acceptance for monitoring and trending of arterial oxygen saturation in healthy subjects. PMID- 2322757 TI - A surrogate arm for evaluating the accuracy of instruments for indirect measurement of blood pressure. AB - A surrogate arm, containing an artificial artery, has been developed for evaluating the accuracy of automatic, non-invasive, blood-pressure measuring devices. The surrogate arm produces all of the events associated with the auscultatory and oscillometric methods of measuring blood pressure. The surrogate arm includes a flat artificial artery in a plastic cylindrical chamber, 30 cm in circumference and 25 cm long, that contains an air/water mixture that allows matching the compliance of the human arm. Linear regression lines were obtained to correlate the indirectly (y) and directly (x) measured pressures. For auscultatory systolic pressure y = 1.01x - 1.60, with a correlation coefficient of 0.99. For mean oscillometric pressure y = 1.00x + 0, with a correlation coefficient of 1.00. For phase IV auscultatory (diastolic) pressure, y = 1.02x - 1.40, with a correlation coefficient of 0.96. For phase V auscultatory (diastolic) pressure y = 0.79x + 10.9, with a correlation coefficient of 0.98. PMID- 2322759 TI - Codes and standards. PMID- 2322758 TI - Delegate for results. PMID- 2322760 TI - The Safe Medical Devices Act of 1989: a burden on medical facilities, device manufacturers, and the FDA? PMID- 2322761 TI - Biomedical equipment maintenance: adjusting to the demands of a changing environment. PMID- 2322762 TI - Transferring technology into the health care delivery system: the clinical engineering responsibility. PMID- 2322763 TI - 'Lost and found': some logical and methodological limitations of self-report questionnaires as tools to study cognitive ageing. AB - Laboratory tests show a decline in memory efficiency with age, but may not reflect highly practiced everyday memory skills. Self-rating questionnaires probe memory efficiency in everyday life, but seven logical and methodological problems ambiguate interpretation of the data they yield. To explore these problems, 442 volunteers aged from 50 to 85 years were given the AH 4 IQ tests, Mill Hill Vocabulary Tests, Beck Depression Inventory (BDI), Broadbent Cognitive Failures Questionnaire (CFQ), Sunderland & Harris Memory Failure Questionnaire (MFQ), the 'Lost and Found' Questionnaire (LF, a new domain-specific probe of the variety, frequency and aetiologies of losses of possessions) and two laboratory memory tests. All self-rating questionnaire scores correlated modestly with each other. Counter-intuitively, individuals over 60 years old reported fewer lapses on the LF and on the CFQ. No SRQ scores correlated with performance on laboratory tasks. CFQ scores did not correlate with IQ test scores but high IQ test scorers reported greater recent decline in memory efficiency (MFQ) and greater current frequency of losses of objects (LF). CFQ and LF scores correlated positively with Beck Depression Inventory scores, suggesting some common loading for poor self regard. The results suggest that subjective self-ratings cannot reflect absolute levels of everyday competence, but only the relative success of individuals' adaptations to idiosyncratic environments which, as they age, may change faster than their abilities. However, besides exposing the limitations of self-report techniques, these analyses also suggest practical ways of adapting and using SRQs which may allow us to gain better insights into changes and individual differences in functional efficiency in everyday life. PMID- 2322764 TI - Repetition priming from incomplete faces: evidence for part to whole completion. AB - Two experiments are reported in which subjects' reaction times to make familiarity decisions to the faces of famous people were compared for faces primed by previously seeing (1) the internal features of the same face, (2) the external features of the same face, or (3) a complete version of the same face. Reaction times to faces primed by the internal features, the external features or a complete face were significantly facilitated relative to an 'unprimed' comparison condition, and did not differ one from another. Viewing part of a familiar face on a previous occasion was therefore found to be as effective at priming recognition as seeing a whole face. This finding was demonstrated in Expt 1 for priming from the repetition of stimuli derived from an identical photograph of the same famous person, and in Expt 2 for priming from stimuli derived from a different photograph of the same familiar face. 'Distributed processing' accounts of repetition priming may be more useful than accounts based entirely on episodic records in explaining these results. PMID- 2322765 TI - The relationship between handedness, anxiety and questionnaire response patterns. AB - State and trait anxiety were found to be unrelated to the handedness categories distinguished by Annett (1970) in a sample of volunteers (N = 385). Furthermore, mean scores for 99 male subjects did not differ significantly from those of 293 females. The mean anxiety levels in this study were much more representative of the general population than those reported in a previous similar study by Beaton & Moseley (1984). A suggestion that subjects classified as mixed-handed might show a tendency to avoid extreme responses was not supported. PMID- 2322766 TI - The Kamin blocking effect, incidental learning and psychoticism. AB - The Kamin blocking effect consists in impaired learning of an association between a conditioned stimulus (CS2) and an unconditioned stimulus (UCS) if CS2 is presented simultaneously with a different CS (CS1) already associated with the UCS. It is well established with animal but not human subjects. In the two experiments presented here, the effect was clearly demonstrated with UCS = a computer-presented yellow square, CS1 = a blue square and CS2 = a noise (Expt 1) or two smaller white squares (Expt 2). The Kamin effect has, by some theorists, been attributed to switching of attention away from CS2, which conveys only redundant information. If so, the size of the effect should co-vary with indices of selective attention commonly used with human subjects. As predicted, the blocking effect was found to be smaller in subjects who displayed a high degree of incidental learning in either of two tasks in which intentional vs. incidental learning corresponded to (1) words vs. word position, or (2) a target initial word letter vs. non-target initial letters. We report elsewhere that the blocking effect is absent in acute schizophrenics. In the present experiments, however, there was no systematic relation between any of four measures of psychoticism, or intelligence, and either the blocking effect or incidental learning. PMID- 2322767 TI - Age and year of onset differences in siblings with rheumatoid arthritis. AB - Differences in age of disease onset and calendar year of onset were studied in 46 rheumatoid arthritis (RA) sibling pairs and in unrelated pairs of RA patients attending a hospital clinic. Mean age of onset and calendar year of onset differences in each group were similar. These results support the theory that RA is caused by an interaction of genetic and environmental factors and provide evidence against a single environmental transmissible cause. PMID- 2322768 TI - Why is a frozen shoulder frozen? PMID- 2322769 TI - The prevalence of diffuse idiopathic skeletal hyperostosis in African blacks. AB - The prevalence of diffuse idiopathic skeletal hyperostosis (DISH) was studied in a hospital based population of African Blacks over the age of 40 years. The study was based on an analysis of the lateral chest radiographs of 1000 patients in a retrospective study and 500 consecutive medical admissions in a prospective study. The overall prevalence of DISH was 3.9% (males 3.8% and females 4.2%). There was a rise in the prevalence of DISH with increasing age from 1% in the 40 49 year age group to 13.6% in those over 70 years. The prevalence of diabetes was 52.4% in the 21 patients with DISH who were seen in the prospective analysis. Ankylosing spondylitis, which is associated with HLA-B27, is rare in African Blacks. However, DISH is not uncommon but its prevalence is lower than in a similar hospital based study of Jews in Israel. PMID- 2322770 TI - Eosinophilic fasciitis associated with inflammatory neutrophilic vasculitis. AB - The authors report a case of eosinophilic fasciitis with an histopathological pattern of inflammatory neutrophilic vasculitis associated with the typical inflammatory infiltrate. The presence of this type of vasculitis which may be observed in the initial forms of scleroderma supports the hypothesis of a considerable overlap between these two entities. PMID- 2322771 TI - Regional pain syndrome again. PMID- 2322772 TI - Anaemia of RA and intravenous iron--not laid to rest? PMID- 2322773 TI - The mechanism of muscle calcification. PMID- 2322774 TI - Sjogren's syndrome and diabetes mellitus. PMID- 2322775 TI - Selenium glutathione peroxidase in rheumatoid arthritis. PMID- 2322776 TI - Acute sarcoid arthropathy--an infective cause? PMID- 2322777 TI - Sex, hormones and rheumatoid arthritis: the nun's story. PMID- 2322778 TI - Eosinophilic fasciitis. PMID- 2322779 TI - It is said that elevated erythrocyte sedimentation rate and the elevation of C reactive protein (CRP) may be indicators of continuing joint destruction in rheumatoid arthritis. What then is the explanation for joint destruction in some patients in whom there is no such apparent elevation of either the sedimentation rate of CRP? AB - It is said that elevated erythrocyte sedimentation rate and the elevation of C reactive protein (CRP) may be indicators of continuing joint destruction in rheumatoid arthritis. What then is the explanation for joint destruction in some patients in whom there is no such apparent elevation of either the sedimentation rate or CRP? PMID- 2322780 TI - Geographical clustering of scleroderma in south and west London. AB - Anecdotal observation suggested a local increase in the occurrence of scleroderma within a borough in close proximity to a major airport. Ascertainment of all living cases was attempted within that borough and adjacent boroughs as well as a similar exercise in two further boroughs in close proximity to another major airport. The results showed a higher prevalence of scleroderma in all three study areas compared to that expected based on a population survey in another part of the United Kingdom adopting similar methodology. Further, within the boroughs there was a suggestion that the cases were not uniformly distributed but tended, in part, to cluster in those parts of the study areas that were in fact near to the airports under investigation. The increase in absolute risk was not sufficiently high to be consistent with a major environmental hazard. There is also no biologically plausible hypothesis for these observations. Nevertheless, the observation is of interest and might suggest further lines of inquiry for aetiological research. PMID- 2322781 TI - Moral balance: the effect of prior behaviour on decision in moral conflict. AB - Two studies examined predictions from the 'moral balance' model, according to which moral decisions are affected by evaluation of the actor's moral status based on his/her recent moral history. It was found that people are more willing to allow a deviation to, and believe that this should generate less guilt in, a person who generally behaves morally than in one who generally behaves immorally. It was also found that an unworthy act by a person (self or other) who has recently behaved morally is evaluated less severely than the same act performed by one who has recently behaved immorally. This trend for normative judgements is contrary to that found for descriptive judgements: a person who has recently behaved immorally is perceived as more likely to choose to act improperly and to feel less guilty. This discrepancy between normative and descriptive judgements is analysed in terms of the distinction between attributions to trait as opposed to effort, to trait as opposed to situation, and between those made from the perspective of actors as opposed to observers. PMID- 2322782 TI - Age and social competence in preschoolers' decoding of facial expression. AB - This study examines the relationship between social competence and decoding of emotions in children aged between three and five years. Children were shown videotaped scenarios depicting emotional situations and were asked to choose which of three facial expressions, representing happiness, sadness and fear, would be most appropriate for the character in the situation. Children's level of social competence was assessed by a standardized questionnaire completed by their parents. Results showed that subjects with relatively higher social skills were better decoders than subjects with relatively lower social skills, and that decoding performance improved with age. The results are discussed in terms of the role of non-verbal behavioural skills in general social competence. PMID- 2322783 TI - Predictors and effectiveness of coping with political violence among Palestinian children. AB - Relationships between exposure to political hardships, social-economic status and mother's psychological responses, and children's coping modes, were analysed among 66 Palestinian boys and girls aged 8-14 who lived in the West Bank and the Gaza Strip. The effectiveness of children's coping modes in protecting their mental health from the negative impact of political hardships was also analysed. The coping modes were assessed on the intentional (passive-active), cognitive (defensive-purposive), and emotional (helpless-courageous) levels. The results showed that the more children were exposed to political hardships, the more they employed active and courageous coping modes. Furthermore, the more mothers showed psychological symptoms the more their children used active coping modes. The more political activity the mothers used as a coping mode, the more their children used purposive coping. Exposure to political hardships increased children's psychological symptoms, and none of the children's psychological coping modes were effective in mitigating this relationship. PMID- 2322784 TI - Categorical differentiation and intergroup relationships. AB - In this study we attempted to replicate the well-known Doise & Sinclair (1973) procedure for manipulating category salience, in a different social context. We considered the relationship between two groups of professionals: doctors and nurses, as perceived by 40 members of the superior group. The results did not confirm those obtained by Doise & Sinclair since they showed reduced categorical differentiation when the out-group was evoked in advance of the intergroup evaluations. The implications of these findings for theories of social categorization and social identity are discussed. PMID- 2322785 TI - Papers presented at a meeting of the Vascular Surgical Society of Great Britain and Ireland. Dundee, 23-24 November 1989. Abstracts. PMID- 2322786 TI - Inheritance of colorectal cancer susceptibility. PMID- 2322787 TI - Pouch size: the important functional determinant after restorative proctocolectomy. AB - Sixty-seven patients with a J-shaped ileonanal pouch were studied over a 2-year period with regular recording of sphincter and pouch characteristics and analysis of their role in functional outcome. Although there was a 27 per cent permanent reduction in resting anal pressure (RAP) (P less than 0.001), two-thirds of the patients still had a RAP within the normal range. The mean(s.d.) pouch volume increased during the first year from 132(46) ml to 282(85) ml. RAP was not related to functional outcome and preoperative RAP was not predictive of subsequent function. Large pouch volume and compliance correlated with low defaecation frequency (range of r = 0.27-0.36; P less than 0.05) and good overall function (r = 0.37-0.56; P less than 0.01). The initial pouch volume was predictive of subsequent overall function. The ileal length used for pouch construction predicted subsequent pouch volume (r = 0.48; P less than 0.001) and to some extent functional outcome (r = 0.28-0.37; P less than 0.05). However, the studied variables accounted for only 21 per cent of the total variance of functional outcome. PMID- 2322788 TI - Double contrast barium enema and flexible rectosigmoidoscopy: a reliable diagnostic combination for detection of colorectal neoplasm. AB - The efficiency of double contrast barium enema and flexible rectosigmoidoscopy (to 60 cm) in the assessment of patients with a positive Hemoccult II test in a randomized screening study for colorectal neoplasms was evaluated. A positive test was present in 625 patients, of whom 530 had a complete enema and rectosigmoidoscopic assessment. A carcinoma was diagnosed in 26 and an adenoma greater than or equal to 1 cm in diameter in 71. As a control, 323 patients with a negative assessment repeated the Hemoccult II test and of these 67 had a positive second test, of whom 55 underwent colonoscopy. One carcinoma (Dukes' A) and two adenomas greater than or equal to 1 cm in diameter were diagnosed. The efficiency of the assessment was also checked by rescreening the whole group 1-2 years after the first study and by continuing follow-up. It was found that two more carcinomas and one adenoma greater than or equal to 1 cm in diameter had been overlooked at the primary assessment. The sensitivity for neoplasms greater than or equal to 1 cm in diameter at the primary assessment was 72 per cent for double contrast barium enema and 86 per cent for rectosigmoidoscopy. The sensitivity for the combined methods was 94 per cent and the specificity was 99 per cent. The combination of double contrast barium enema and rectosigmoidoscopy in the primary assessment of patients with a positive Hemoccult II test gives an acceptable result and immediate retesting of those with a negative assessment is not necessary. PMID- 2322789 TI - Faecal occult blood screening for colorectal neoplasia: a randomized trial of three days or six days of tests. AB - Haemoccult, a guaiac test for faecal occult blood, detects 56-78 per cent of asymptomatic carcinomas when performed over 3 days. In patients with known colorectal cancer the sensitivity of the test for neoplasia is increased by extending the test period to 6 days. We report the first randomized comparison of 3 day with 6 day testing in asymptomatic individuals. 35,184 age and sex matched individuals were randomly allocated to receive Haemoccult over 3 or 6 days. The tests were completed by 10,176 (57.8 per cent) of the 17,616 offered 3 day Haemoccult and 9461 (53.9 per cent) of the 17,568 offered 6 day Haemoccult, a significant decrease in compliance (P less than 0.001). Of the 3 day Haemoccult tests 131 (1.29 per cent) were positive, significantly fewer than the 160 (1.69 per cent) positive tests after 6 day Haemoccult (0.01 less than P less than 0.02). Investigation of subjects with a positive test revealed 20 carcinomas (1.14 per 1000 offered and 1.97 per 1000 completing the test) in the 3 day group and 24 carcinomas (1.37 per 1000 offered and 2.54 per 1000 completing the test) after 6 day Haemoccult tests (0.5 less than P less than 0.7 for those offered the test and 0.3 less than P less than 0.5 for those completing it). After 3 day Haemoccult 112 adenomas in 76 persons were detected (4.31 per 1000 offered and 7.47 per 1000 completing the test). In the 6 day group 123 adenomas in 83 persons (4.72 per 1000 offered and 8.77 per 1000 completing the test) were detected (0.5 less than P less than 0.7 for those offered the test and 0.3 less than P less than 0.5 for those completing it). Large adenomas were found in 27 individuals after 3 day testing (1.53 per 1000 offered the test and 2.65 per 1000 completing it) and in 35 individuals after 6 day testing (1.99 per 1000 offered the test and 3.70 per 1000 completing it) (0.3 less than P less than 0.5 for those offered the test and 0.1 less than P less than 0.2 for those completing it). This study has not demonstrated a significant increase in the yield of neoplasia in asymptomatic subjects offered Haemoccult over 6 days. However there was a significant decrease in compliance and a higher rate of colonscopy in those offered 6 day testing. PMID- 2322790 TI - Operative findings in patients with early forms of gallbladder cancer. AB - Of 52 patients diagnosed as having gallbladder cancer in a 2-year period, 15 had no evidence of serosal involvement. Four of these 15 patients had tumour confined to the mucosa and did not undergo reoperation while 11 patients underwent lymph node dissection and hepatic wedge resection at a second operation. The correct diagnosis was suspected before the first operation in only one of 11 patients undergoing reoperation; the tumour was found microscopically in seven patients. Of the 11 patients who underwent reoperation, five had lymph node involvement, and three of these patients had both liver and lymphatic involvement. Our results underline the difficulty of establishing the diagnosis of gallbladder cancer before operation and the lack of major morbidity and mortality suggests that there may be value in reoperating on patients found to have gallbladder carcinoma without serosal involvement. Further follow-up is required to assess the long term value of this approach. PMID- 2322791 TI - Management of gastric variceal haemorrhage. AB - From March 1979 to April 1988 nine patients with hepatic cirrhosis have presented with acute variceal haemorrhage from gastric varices. Of six patients who underwent emergency laparotomy those with modified Child's grade C (n = 3) died within 30 days of surgery. Six patients have been followed for 2 years or longer. In the three patients who underwent under-running of gastric varices alone, two patients developed oesophageal varices at 3 and 14 months, respectively, and in the third patient gastric varices recurred 3 years after surgery. In the remaining three patients, additional left gastric vein ligation was not associated with recurrence of gastric varices or the development of oesophageal varices. PMID- 2322792 TI - Non-preservation of the pylorus in resection of pancreatic cancer. PMID- 2322793 TI - Towards decreasing the relaparotomy rate in the Peutz-Jeghers syndrome: the role of peroperative small bowel endoscopy. AB - Relaparotomy occurs commonly in patients with the Peutz-Jeghers syndrome, and at quite short intervals. Between 1943 and 1987 laparotomies were performed on 54 occasions in 23 patients with the Peutz-Jeghers syndrome who at some time came under the care of St. Mark's Hospital. In four patients repeat laparotomy was performed within a single year. Between 1987 and 1989 a further five patients have undergone laparotomy with on-table small bowel endoscopy. External palpation and small bowel transillumination failed to demonstrate 17 out of a total of 45 hamartomas (38 per cent). Of these 17 polyps identified endoscopically, 11 (65 per cent) were sufficiently large that a snare was used to remove them. We recommend peroperative enteroscopy as an adjunct to surgery in the Peutz-Jeghers syndrome. PMID- 2322794 TI - Pancreatic denervation for pain relief in chronic alcohol associated pancreatitis. AB - To denervate the pancreas of sensory afferents, 15 patients with intractable pain of chronic alcohol induced pancreatitis underwent left transthoracic splanchnicectomy with concomitant bilateral truncal vagotomy. All were malnourished and 11 were addicted to opiates. No respite had been obtained from 33 previous operative procedures. Each patient experienced almost immediate pain relief. Five, however, later had return of pain, but only to the right epigastrium. These five then underwent right transthoracic splanchnicectomy, after which four noted complete and apparently permanent disappearance of pain. In those 14 with a successful outcome there has been a 29 per cent mean increase in body weight, break of hard drug addition in ten of the 11 so afflicted, and return to gainful work or a relatively normal lifestyle in all 14 at a mean follow-up of 16 months. Although 11 of the 14 do have delayed gastric emptying, only one has required a drainage procedure. There have been no other late complications. This approach for control of incapacitating pain in chronic pancreatitis is both safe and simple and at the same time it appears to be reasonably reliable. PMID- 2322796 TI - Femoral hernia: an avoidable source of surgical mortality. PMID- 2322795 TI - Progressive pneumoperitoneum in the management of giant incisional hernias: a study of 41 patients. AB - Forty-one patients (17 men and 24 women) were treated with progressive pneumoperitoneum before repair of giant incisional hernias. The pneumoperitoneum was induced using nitrous oxide gas and a laparoscopic insufflator, and was topped up every other day for a mean of 5.5 days with a total injection of 23.2 litres of nitrous oxide. The pneumoperitoneum was well tolerated in 30 patients, caused a mild temporary pain in 10 patients and a sharp pain in one patient; no serious side-effects occurred. All the patients underwent surgery to repair their hernias, 40 patients were available for follow-up for a mean of 25.3 months, only two hernias recurred both within 4 months of the operation. PMID- 2322797 TI - Indications for conservative management of acute scrotal pain in children. AB - Forty-three boys who presented with acute scrotal pain were studied retrospectively. Of these, 40 had torsion of scrotal contents. Torsion of testicular appendages, a self limiting condition, tended to present later than testicular torsion (P = 0.002). The testis was saved in all 11 cases of testicular torsion explored within 12h of the onset of pain but orchidectomy was required in four who presented later. In 11 cases, a torted testicular appendage diagnosed as a tender nodule was found on examining the upper pole of the testis. The remaining 14 cases of torted appendage were diagnosed at operation because testicular torsion could not be excluded due to scrotal swelling. Most (12) of this operated group were not seen until 3 days after the onset of pain. This study suggested that urgent operation was unnecessary in those in whom a tender nodule was found (pathognomonic of a torted appendage) and in those presenting after more than 24h of pain with scrotal erythema and oedema. The likely diagnosis in the latter case is a torted appendage and in cases of torsion of the testis there is no prospect of salvage at this stage. These guidelines were applied to a group of 20 boys studied prospectively. In eight, all with less than 24h of pain, immediate exploration was undertaken and testicular torsion was confirmed in six. The remaining 12 fulfilled the criteria for conservative management and were observed. All had normal testes at late review. Careful clinical assessment in boys with scrotal pain indicates which cases may be treated by non-operative management without fear of losing a salvageable testis. PMID- 2322798 TI - Skeletal muscle enzyme activities and metabolic substrates during exercise in patients with postoperative fatigue. AB - Subjective fatigue was quantified before and 20 days after uncomplicated elective abdominal surgery in 12 patients and compared with changes in heart rate, enzyme activities and skeletal muscle substrates before and after bicycle exercise for 10 min at 65 per cent of patients' preoperative maximum work capacity. Fatigue increased from a mean(s.e.m.) preoperative level of 2.5(0.5) arbitrary units to 4.6(0.5) on postoperative day 20 (P less than 0.01). Body-weight, triceps skinfold thickness and arm circumference decreased postoperatively (P less than 0.02). Postoperative values of muscle enzyme activities indicative of oxidative phosphorylation capacity (citrate synthase and 3-OH-acyl coenzyme A dehydrogenase) were lower than preoperative values (P less than 0.05). Lactate dehydrogenase was unaltered and resting values of muscle glycogen and adenosine triphosphate were higher after operation (P less than 0.05). In response to exercise, heart rate, muscle glucose, glucose-6-phosphate and lactate increased (P less than 0.05), while muscle glycogen and creatine phosphate decreased (P less than 0.05). Increase in postoperative fatigue correlated with the increase in heart rate (P less than 0.05), while no significant correlations were found between fatigue and muscle parameters. Our results suggest that lack of exercise and malnutrition may be of importance in the decrease in work capacity and in fatigue after operation. PMID- 2322799 TI - Immunodeficiency following splenectomy in the early postimmunization period. AB - Splenectomy is associated with an increased risk of serious infection with encapsulated micro-organisms in a small number of individuals. The immunological defects in this state are unclear. We have investigated in rabbits the effect of splenectomy, before and after primary immunization with a specific antigen (sheep erythrocytes) similar in structure to the pneumococcal capsular antigen, on the organ localization of antibody forming cells and the long-lived memory cells. Antibody forming cell and memory cell assays were performed at intervals up to day 270 after primary immunization. Antibody titres following secondary immunization were also measured. The results show that the major site of antibody forming cells is in the spleen following primary immunization of the untreated rabbit and that antibody forming cells subsequently migrate to the lymph nodes and thymus. On the other hand, in rabbits splenectomized before primary immunization the major site of the antibody forming cells is the peripheral lymph nodes. These rabbits also gave good secondary immune responses. However, splenectomy 40 days after primary immunization results in a poor secondary immune response, indicating that essentially all the antibody forming cells following primary immunization were localized in the spleen at the time of splenectomy. PMID- 2322800 TI - Fine-wire localization and biopsy of non-palpable breast lesions. AB - We have undertaken fine-wire localization and biopsy of 130 impalpable breast lesions identified by mammography and considered suspicious of malignancy. Histologically 22 of these lesions were invasive carcinomas and 24 were in situ carcinomas (35 per cent malignant). Twenty-nine per cent of the lesions were identified during the screening of asymptomatic women. In the remainder, the presenting symptoms bore no relation to the eventual histological diagnosis. Clusters of microcalcification were more often malignant than were abnormal soft tissue masses. Malignancy in the absence of microcalcification was almost always invasive. PMID- 2322801 TI - Assessment of surgical excision during breast conservation surgery by intraoperative two-dimensional specimen radiology. PMID- 2322802 TI - Measurement of serum thyroglobulin is of value in detecting tumour recurrence following treatment of differentiated thyroid carcinoma by lobectomy. AB - Serum thyroglobulin was measured in 243 samples from 84 patients (20 men and 64 women, with a mean age of 48.9(14) years) with differentiated thyroid carcinoma treated by lobectomy, and in 58 patients treated by total thyroidectomy. Both groups were given thyroxine to suppress thyroid stimulating hormone (TSH). Three patients in the lobectomy group and eight in the thyroidectomy group had evidence of tumour recurrence. Serum thyroglobulin concentration was elevated in the presence of known recurrent tumour (P less than 0.001) irrespective of the type of operation, and in its absence tended to be higher in the lobectomy than in the thyroidectomy group (median 4 micrograms/l versus 2 micrograms/l, P less than 0.05). Serum thyroglobulin levels of less than 10 micrograms/l could confirm the absence of otherwise known tumour recurrence in both groups with a specificity of 100 per cent, and sensitivities of 80 per cent and 86 per cent in the lobectomy and thyroidectomy groups respectively. Exclusion of samples liable to spurious elevation of thyroglobulin improved the sensitivity in the lobectomy group to 92 per cent. Despite the presence of residual thyroid tissue, measurement of serum thyroglobulin can exclude the presence of significant metastases in most patients following lobectomy for thyroid carcinoma. PMID- 2322803 TI - Infected false aneurysms in the groin of intravenous drug abusers. AB - The hazards of dealing with infected false femoral aneurysms resulting from intra arterial narcotic injection are highlighted in six patients. Two patients were human immunodeficiency virus positive and three patients were hepatitis B surface antigen positive. Because of these infections exploration of groin swellings as presumed soft tissue abscesses is potentially hazardous without proper proximal vascular control. All patients underwent reconstruction following arterial ligation and five grafts became infected, with life threatening haemorrhage occurring in four patients. Five grafts have subsequently occluded or have been removed without loss of limb viability, although two patients have been regrafted. A high index of suspicion and assessment by a vascular surgeon, with angiography if indicated, is required in any intravenous drug abuser presenting with a groin swelling following injection. Because of the great risk of graft infection, it is suggested that ligation and debridement alone be carried out, with immediate arterial reconstruction only for non-viability. PMID- 2322804 TI - Intra-arterial injection of oral medication in HIV positive drug addicts. PMID- 2322805 TI - Hepatic haemodynamic changes after portacaval anastomosis in normal, cirrhotic and chronic prehepatic portally hypertensive rats. AB - Radioactive microspheres were used to determine the hepatic haemodynamic response to portacaval anastomosis in normal, cirrhotic and chronic prehepatic portally hypertensive rats 20 days after operation, and in normal rats 2 months after operation. After 20 days portacaval anastomosis caused a decrease in liver mass only in normal and cirrhotic animals, whereas hepatic arterial blood flow per unit of mass increased in normal (+488 per cent), cirrhotic (+191 per cent) and prehepatic portally hypertensive rats (+133 per cent). Despite these facts, animals with portacaval anastomosis showed a reduced hepatic total perfusion (arterial plus portal inflow) per unit of mass with respect to controls in normal (-53 per cent) and cirrhotic rats (-68 per cent), but not in those with prehepatic portal hypertension. Comparing studies carried out at 2 months with those performed 20 days after portacaval anastomosis in normal rats, some recovery of liver mass and total liver blood flow was observed. In conclusion, portacaval anastomosis produced a limited increase in hepatic arterial blood flow which was unable to preserve liver mass and its total perfusion in normal and cirrhotic animals. In contrast, portacaval anastomosis did not significantly alter liver mass or its perfusion in animals with chronic prehepatic portal hypertension, as both values were previously diminished in controls. Thus, the risk of liver failure after portacaval anastomosis is higher in normal and cirrhotic rats than in those with chronic prehepatic portal hypertension. PMID- 2322806 TI - Diffuse cavernous haemangioma of the rectum in childhood. PMID- 2322807 TI - Gastric cancer: a 25-year review. PMID- 2322808 TI - Essential fatty acids. PMID- 2322809 TI - Cryotherapy for liver metastases. PMID- 2322810 TI - Electrocardiographic guided placement of central venous catheters. PMID- 2322811 TI - The corpus callosum and cerebral speech lateralization. AB - In order to specify the callosal involvement in the establishment of cerebral lateralization, a dichotic listening task was administered to six subjects with congenital absence of the corpus callosum, two callosotomized patients, and two hemispherectomized patients. The acallosal subjects were also compared to six subjects matched for age, sex, and hand dominance as well as to six subjects also matched for IQ. Our findings indicate that language functions, as assessed by dichotic listening performance, are more strongly lateralized in callosal agenesis subjects than in IQ-matched normal controls. Our results also reveal that hemispherectomized patients typically show a strong ear-advantage favoring the ear contralateral to their remaining hemisphere. Callosotomized patients, on the other hand, show a more variable pattern of results that seems to be related to the postsurgical time interval. Finally, our findings suggest that there might be a relationship between IQ and lateralization in subjects with borderline or mild deficiency. PMID- 2322812 TI - Semantic errors in a deep dyslexic. AB - A case of a Swedish-speaking deep dyslexic is reported whose semantic paralexias appeared to result mainly from a lexical retrieval failure in oral reading. He was able to draw correct pictures of the written words for which he had simultaneously produced a semantically erroneous oral reading response. Repeated attempts to correct paralexic responses were common, indicating that the patient was often aware of the errors. His lexical retrieval problems and semantic errors extended to naming as well, and the results support Nolan and Caramazza's (1982, Brain and Language, 16, 237-264), dual-deficit model of deep dyslexia. PMID- 2322813 TI - Impaired activation of the phonological lexicon: effects upon oral reading. AB - The role of the phonological lexicon in oral reading is examined in a patient with a small focal left hemisphere lesion. Impaired access to the patient's phonological lexicon is suggested by a number of findings, including the production of phonemic errors across a variety of tasks; increasing difficulty in word production with increasing word length; and difficulty on tests of homophone and rhyme judgments. Two competing models of reading are tested: the nonlexical ("rules") and the lexical ("no-rules") models. The rules model predicts that a disturbance in the phonological lexicon will result in surface alexia; the no rules model predicts phonological alexia. Results indicate that the patient's reading is most similar to phonological alexia, providing support for the no rules model. The applicability of the no-rules model to other forms of acquired alexia is explored. PMID- 2322814 TI - Enhancement of naming in nonfluent aphasia through gesture. AB - In a number of studies that have examined the gestural disturbance in aphasia and the utility of gestural interventions in aphasia therapy, a variable degree of facilitation of verbalization during gestural activity has been reported. The present study examined the effect of different unilateral gestural movements on simultaneous oral-verbal expression, specifically naming to confrontation. It was hypothesized that activation of the phylogenetically older proximal motor system of the hemiplegic right arm in the execution of a communicative but nonrepresentational pointing gesture would have a facilitatory effect on naming ability. Twenty-four aphasic patients, representing five aphasic subtypes, including Broca's, Transcortical Motor, Anomic, Global, and Wernicke's aphasics were assessed under three gesture/naming conditions. The findings indicated that gestures produced through activation of the proximal (shoulder) musculature of the right paralytic limb differentially facilitated naming performance in the nonfluent subgroup, but not in the Wernicke's aphasics. These findings may be explained on the view that functional activation of the archaic proximal motor system of the hemiplegic limb, in the execution of a communicative gesture, permits access to preliminary stages in the formative process of the anterior action microgeny, which ultimately emerges in vocal articulation. PMID- 2322815 TI - The effects of right hemisphere damage on the pragmatic interpretation of conversational remarks. AB - The ability to interpret conversational utterances was assessed in a group of 12 male patients with unilateral right hemisphere brain damage (RHD) and 12 non brain-damaged, age-matched male control subjects. Subjects listened to short vignettes which described both the affective tone of the relationship between a speaker and an actor, and the actor's performance on a task. Each vignette concluded with the speaker characterizing the actor's performance. In half of the items, the speaker's utterance was literally true; in the other half, the utterance was literally false and invited a nonliteral interpretation. Results showed no appreciable differences in the performance of control subjects and RHD patients when interpreting literally true utterances. In contrast, the two groups differed reliably when interpreting the pragmatic intent of nonliteral utterances: Control subjects used information about both the actor's performance and the speaker-actor relationship, while RHD patients demonstrated difficulty in using the information about the speaker-actor relationship. Results have implications for patients' understanding of essential elements of conversations, such as characters' internal states and their intentions in employing different forms of literal and nonliteral language. PMID- 2322816 TI - Disruption of semantic influence on writing following a left prefrontal lesion. AB - We report a patient with impaired spontaneous writing, written naming, and homophone spelling, consistent with a disruption of semantic influence on writing. However, writing to dictation by both the phonological and lexical spelling systems was intact. In addition, general semantic abilities were spared, as indicated by preserved auditory and reading comprehension. We propose that our patient could not incorporate meaning into writing because of a disruption of both direct and indirect connections between semantics and the orthographic output lexicon. The writing dysfunction was accompanied by a similar impairment of speech output, suggesting that it was part of a more general disturbance of semantic influence on language production following left prefrontal damage. PMID- 2322817 TI - Neural systems contributing to acetylcholinesterase histochemical staining in primary visual cortex of the adult rat. AB - Histochemical studies demonstrate that cortical area 17 (primary visual cortex) of the adult rat displays a characteristic laminar pattern of acetylcholinesterase (AChE) activity. While AChE-positive axons are found throughout the cortical layers, most intense staining occurs in a band that corresponds to layer V and the deep portion of layer IV. The present studies were directed toward determining the neural systems containing this AChE activity. Unilateral electrolytic or excitatory amino acid induced lesions of the basal forebrain result in reductions of AChE staining in ipsilateral visual cortex, particularly in layers IV and V. Electrolytic or scalpel lesions, placed in white matter underlying dorsal and lateral neocortex to interrupt basal forebrain projections to visual cortex, also reduce AChE staining in visual cortex. Lesions in the cingulate bundle and supracallosal stria reduced AChE staining retrosplenial cortex but did not affect staining visual cortex. Placement of electrolytic lesions in the hypothalamus produced no detectable change in the pattern of AChE in visual cortex. Electrolytic lesions in the midbrain tegmentum, placed to interrupt ascending axons from brainstem monoamine neurons, produced no detectable change in the pattern of AChE in visual cortex. Placement of lesions in the dorsal thalamus that include all of the dorsal lateral geniculate nucleus did not alter AChE staining in visual cortex. The results indicate that AChE activity in adult visual cortex is found primarily within afferent axons from the basal forebrain system. These data demonstrate further that the AChE staining characteristic of adult visual cortex is associated with neural systems that are distinctly different from those associated with AChE staining in visual cortex of the infant rat. PMID- 2322818 TI - Calibers and microtubules of nerve fibers: differential effect of undernutrition in developing and adult rats. AB - Sural nerves of 9-week-old rats undernourished since birth, and of adult rats food-restricted for 27 and 48 days, were studied to explore the effect of severe undernutrition on the caliber and microtubules of axons in growing and non growing animals. In 9-week-old undernourished rats, the number and caliber of myelinated fibers were normal while the cross-sectional area of non-medullated fibers was 29% smaller than controls. By contrast, in adult undernourished rats the cross-sectional area of myelinated fibers was affected sooner and to a greater extent (-28%) than that of non-medullated fibers (-23%). Regardless of age, in both controls and in undernourished rats non-medullated fibers of equal caliber had similar microtubular content. The same was found in 3-microns myelinated axons. These findings indicate that food restriction affects proportionately caliber and microtubules of axons. It is proposed that the anatomy of the axon is in a dynamic equilibrium and that microtubules participate in the specification of the axonal caliber. PMID- 2322819 TI - Neuronal responses related to reinforcement in the primate basal forebrain. AB - In the present study neurones recorded in the substantia innominata, the diagonal band of Broca and a periventricular region of the basal forebrain responded differentially to stimuli signalling the availability of fruit juice or saline obtained by making lick responses in two different visual discrimination tasks. The activity of certain neurones reflected the rewarding nature of stimuli used to signal the availability of juice in the tasks, responding to the sight and delivery of both foods and syringes used to deliver juice in tests in which behavioural responses were irrelevant. The activity of other neurones reflected aversion, responding to task stimuli signalling availability of saline and to syringes used to deliver saline to the mouth. In another task an auditory cue that signalled the availability of juice elicited neuronal responses. These neurones also responded to a tone cue used to signal the onset of the trial, and during certain mouth and arm movements which the monkey used to obtain reinforcement. The responses of these differential neurones were similar in most respects in all 3 regions of the basal forebrain. Thus these neurones respond to a range of visual and auditory stimuli that monkeys have learned can be used to obtain reinforcement, but not on the basis of sensory properties such as shape or colour of the stimuli. We conclude that the reinforcement-related nature of the neuronal signal from the basal forebrain could be used to facilitate processing in cortical regions, optimising the functioning of sensory, motor and association cortices, thus increasing the probability of responding appropriately to learned environmental contingencies. We suggest that the properties of these neurones are due to afferent inputs from ventromedial regions of the prefrontal and temporal cortices and amygdala. PMID- 2322820 TI - The effect of a conditioning lesion on sudomotor axon regeneration. AB - The effects of a conditioning lesion on the rate of sudomotor axon regeneration were judged by the recovery of sweat gland (SG) secretion after cholinergic stimulation. Three groups of mice were given a conditioning lesion by crushing the sciatic nerve at mid-thigh 4, 7, and 14 days before a test lesion. A 4th group received a conditioning crush of the tibial nerve at the ankle 7 days before the test lesion. Control mice had a single test lesion. SG reinnervation in control mice began 19 days after the test lesion, and was functionally complete by 41 days. In groups with the conditioning lesion 4, 7, and 14 days before the test operation, the first reactive SGs reappeared at 16, 15, and 16 days respectively after the test lesion, and maximal recovery occurred by 33, 32, and 39 days. In mice with the distal conditioning lesion, reinnervation began at 19 days and was maximal by 36 days. In summary, a nerve conditioning lesion placed from 4 to 14 days prior to and at the same site as a test lesion significantly accelerated the growth rate of the fastest regenerating unmyelinated sudomotor axons and reduced the time until most SGs were reinnervated. A more distally placed test lesion reduced the interval for recovery. PMID- 2322821 TI - Kappa 2-bungarotoxin and kappa 3-bungarotoxin: two new neuronal nicotinic receptor antagonists isolated from the venom of Bungarus multicinctus. AB - Neuronal nicotinic acetylcholine receptors are recognized with high affinity by two snake venom kappa-neurotoxins, kappa-bungarotoxin and kappa-flavitoxin. Native and radiolabeled kappa-neurotoxins have been used to localize and quantitate neuronal nicotinic receptors in a variety of species. We now report the identification of two new kappa-neurotoxins. kappa 2-Bungarotoxin and kappa 3 bungarotoxin were purified from the venom of Bungarus multicinctus collected in the province of Guangdong, China. kappa-Bungarotoxin has as yet not been found in this venom, although it is the only kappa-neurotoxin to be isolated thus far from Taiwanese Bungarus multicinctus. The geographical separation of Guangdong and Taiwan might account for this evolutionary divergence within the species. Both of the new kappa-neurotoxins are potent antagonists of nicotinic transmission in the chick ciliary ganglion. kappa 3-Bungarotoxin, the least potent of the kappa neurotoxins, produces a complete blockage of nicotinic transmission in 60 min at 250 nM. Protection experiments using the short-acting nicotinic antagonists dihydro-beta-erythroidine and (+)-tubocurarine demonstrate that kappa 2 bungarotoxin blocks transmission by binding to the acetylcholine recognition sites of neuronal nicotinic receptors. The isoelectric point of kappa 2 bungarotoxin (pI = 8.9) is similar to that of kappa-bungarotoxin and kappa flavitoxin, but kappa 3-bungarotoxin is considerably more basic, with pI greater than 11. Partial amino acid sequences are reported for both kappa 2-bungarotoxin and kappa 3-bungarotoxin. These sequences show a high degree of homology (approximately 80%) with other kappa-neurotoxins, and allow the determination of the critical differences between the kappa-neurotoxins and the structurally related alpha-neurotoxins. For example, all 4 kappa-neurotoxins lack a tryptophanyl residue which is invariant and important for function in the alpha neurotoxins. The kappa-neurotoxins also differ from the alpha-neurotoxins by having an invariant prolinyl residue at a critical sequence position. Heterodimers were detected consisting of one subunit each of kappa 2-bungarotoxin and kappa 3-bungarotoxin. These heterodimers, which form between any combination of two kappa-neurotoxins, appear to be physiologically active and confirm that a further distinction between kappa-neurotoxins and alpha-neurotoxins is the strong tendency of the former to self-associate in solution. The present results help to establish the definition of 'kappa-neurotoxin'. These snake toxins are now being used by a number of laboratories in physiological and biochemical experiments on neuronal nicotinic receptors from a variety of species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2322822 TI - Kindling with stimulation of the dentate gyrus. I. Characterization of electrographic and behavioral events. AB - Once daily for 60 days, hooded rats received unilateral high-frequency stimulation in the hilus of the dentate gyrus (DG), at an intensity sufficient to evoke epileptiform afterdischarge (AD). Although most rats eventually developed generalized stage-5 seizures (Generalized group), some did not progress beyond partial stage-1 or stage-2 seizures (Partial group). Hilar kindling also displayed several other characteristics that distinguished it from typical limbic kindling, including low rate of development, marked instability of the seizures, and little or no growth in duration of AD. PMID- 2322823 TI - Kindling with stimulation of the dentate gyrus. II. Effects on evoked field potentials. AB - Once daily for 60 days, male hooded rats received unilateral high-frequency stimulation in the hilus of the dentate gyrus (DG), at an intensity sufficient to evoke afterdischarge (AD). Every 2nd day, evoked potentials were recorded from the hilus following stimulation of the PP with single 0.1 ms pulses at 6 current intensities. Changes in synaptic excitability of the dentate granule cells were monitored by measuring the amplitudes of the population spikes; changes in the strength of excitatory synaptic transmission were monitored by measuring the slopes of the excitatory postsynaptic potentials (EPSPs). Control rats, which were not given kindling stimulation, were tested for changes in synaptic transmission and excitability in the same way, at comparable times. In general, hilar stimulation resulted in a large decrease in population spike amplitudes to below baseline and control levels, accompanied by a paradoxical potentiation of EPSPs. Population spike amplitudes decreased more in rats that developed generalized stage-5 seizures (Generalized group) than in rats that did not progress beyond partial seizures despite 60 days of stimulation (Partial group). Conversely, EPSP slopes increased more in the Partial group than in the Generalized group. These results suggest that kindling stimulation may potentiate responsiveness of the directly activated dentate granule cells to inputs from the PP, but at the same time suppress the output of the granule cells resulting from this input. Furthermore, the results indicate that kindling is more closely allied to the suppression of output than to the potentiation of responsiveness to input. PMID- 2322824 TI - Neural grafts attenuate behavioral deficits produced by early radiation-induced hypoplasia of fascia dentata granule cells. AB - Localized X-irradiation of the mitotic cells in the neonatal rat hippocampus produces a discrete hypoplasia of the fascia dentata granule cell layer. This brain damage inhibits the acquisition of a passive avoidance task, and stimulates spontaneous perseverative turning (without reversals) in a plastic hemisphere apparatus. Here we report how transplantation of fetal brain tissue can attenuate these radiation-induced behavioral deficits. The partially shielded cerebral hemispheres of neonatal rats received fractionated exposures to 13 Gray (Gy) of X rays during the first 16 days post partum. This procedure depleted 90% of the hippocampal granule cells while sparing other brain areas. Control animals were sham irradiated. Baseline behavioral tests were conducted when subjects reached an average age of 147 +/- 4 days. We recorded behavioral parameters known to be sensitive to hippocampal damage: (1) passive avoidance performance, and (2) perseverative spontaneous turning without reversals. Irradiated subjects later (average age = 182 +/- 4 days) received intracerebral transplants of either fetal (E20-21) neurons/neuronal precursors from the fascia dentata or cerebral cortex (control grafts). Additional controls (both irradiated and sham-irradiated) experienced sham surgical procedures or received no surgical manipulation. Two post-surgical behavioral retests were accomplished when rats were 265 +/- 5 and 351 +/- 6 days old. Rats were then sacrificed and brains were treated histologically to assess radiation-induced brain damage, graft survivability and graft locus. Both hippocampal and cerebral cortex grafts generally facilitated performance on the passive avoidance task. This effect was most prominent during the first post-surgical test. Hippocampal transplants (especially those found to reside in the damaged hippocampus) also significantly attenuated perseverative spontaneous rotation at the time of the final post-surgical test series. Cortex grafts found within the damaged hippocampus did not ameliorate perseverative movements, while cortex grafts located outside the hippocampus significantly reduced this behavioral deficiency. These data suggest that selected behavioral deficits may be attenuated by transplanting fetal neural tissue long after early radiation-induced brain damage. The success of these procedures depends on a number of factors including: (1) the behaviors chosen for analysis, (2) the time after transplantation that behavioral tests are conducted, and (3) the source and final location of the donor neural tissue. PMID- 2322825 TI - Long-term stability of the place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats. AB - Over 90% of all spontaneously active hippocampal pyramidal cells in freely moving rats signal the animal's spatial position by reliably changing their firing rate each time the animal enters a given place within an environment. This place-field activity exhibits plasticity when specific environmental variables are manipulated. Indeed, the hippocampus is perhaps best known as a system that serves as a model of neuronal plasticity. Although place-field activity has previously been examined only over relatively short experimental sessions, this behavioral correlate of hippocampal functional activity has been assumed to exhibit stability rather than plasticity in the absence of environmental changes. The present study shows that hippocampal neurons have stable place-field correlates that persist over very long periods of time. Single-unit activity was chronically recorded from the dorsal hippocampus of rats foraging repeatedly in a stable spatial environment. The location of the place fields of all units were stable over all time periods tested, for intervals up to 153 days in duration. The consistency of the information conveyed by this single-unit activity in a fixed spatial environment indicates that stability of neuronal activity may be as important as plasticity in the integrated processing of information that occurs in the hippocampus and throughout the nervous system. PMID- 2322826 TI - Age-related increase in soluble and cell surface-associated neurite-outgrowth factors from rat muscle. AB - While the number of nerve terminals per endplate decreases with age in the rat extensor digitorum longus (EDL) muscle, the number of endplates exhibiting ultraterminal sprouting, characteristic of denervation, increases. To determine if these changes associated with aging are accompanied by alterations in the production of muscle-derived neurite-outgrowth factors, we examined the effects of soluble and cell surface-associated components from innervated and denervated 10- and 25-month rat EDL muscles on a motoneuron-enriched fraction of embryonic chick spinal cord cells in vitro. Cells were cultured for 72 h with muscle extract or on muscle cross-sections. While soluble components of the extract affected initiation of neurite outgrowth, muscle cell surface-associated molecules influenced neurite elongation. Both muscle extract and muscle cross sections from 10-month denervated animals were more effective in promoting neurite outgrowth than 10-month innervated muscle. There was no difference between 25-month innervated and 25-month denervated muscle. However, 25-month innervated and denervated muscles were significantly more effective in promoting neurite outgrowth than 10-month innervated muscle, but not different from 10 month denervated muscle. These results suggest that an age-related increase in muscle-derived soluble and cell surface-associated neurite-outgrowth factors may contribute to denervation-like morphological changes associated with aging at the neuromuscular junction. PMID- 2322827 TI - Evidence for spatiotemporal firing patterns within the auditory thalamus of the cat. AB - Multiple spike trains were recorded in the auditory thalamus of cats. Each unit was studied before, during and after cooling of the ipsilateral primary auditory cortex, during spontaneous activity and acoustically evoked activity. The search for spatiotemporal firing patterns provided evidence that excess of patterns does exist and that the acoustical stimulation increased their number. Cortical cooling did not affect the probability of finding the firing pattern. PMID- 2322828 TI - The selective adenosine A2 receptor agonist, CGS 21680, is a potent depressant of cerebral cortical neuronal activity. AB - The A2 selective adenosine receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5' N-ethylcarboxamidoadenosine (CGS 21680) depressed the spontaneous, acetylcholine- and glutamate-evoked firing of rat cerebral sensorimotor cortical neurons. Iontophoretically applied CGS 21680 was equipotent with adenosine as a depressant and its actions were antagonized by 8-p-sulphophenyltheophylline applied from another barrel of the multibarrelled micropipette. The observation of a potent depressant action of a selective A2 receptor agonist suggests that A2 receptors are involved in the modulation of cerebral cortical neuronal firing by adenosine. PMID- 2322829 TI - Adenosine antagonists alter the synaptic response to in vitro ischemia in the rat hippocampus. AB - Exposure of the submerged hippocampal slice to in vitro ischemic conditions (superfusion with hypoxic medium lacking glucose) resulted in a progression of changes in the orthodromically evoked response recorded from the CA1 pyramidal region. There was an early depression of the population spike with no change in the presynaptic fiber volley, followed by a transient return of the population spike and, finally, a complete loss of both the population spike and fiber volley. The adenosine A1 subtype-selective antagonists, 8-phenyltheophylline (8 PT) and 8-cyclopentyltheophylline (8-CPT), greatly attenuated the early depression of the population spike such that the initial loss of the population spike was associated with the loss of the fiber volley. This result suggests that the initial loss of synaptic function in the hippocampal slice during exposure to in vitro ischemic conditions is due to increased levels of the inhibitory neuromodulator, adenosine. PMID- 2322830 TI - Ultrastructural observations of non-selective effects of ricin treatment (RCA 120) in the rat dorsal root ganglion. AB - The effects of ricin (RCA-120) on non-injected dorsal root ganglion (DRG) cells, sharing the same DRG as the injected ones, were studied after ricin injections into the tibial nerve and B-HRP injections into the peroneal nerve. Numerous DRG cells containing B-HRP reaction product and exhibiting signs of advanced degeneration were observed. The findings suggest that ricin may be released from dying injected DRG neurons and taken up by adjacent non-injected DRG cells, which subsequently degenerate. PMID- 2322831 TI - Action potentials in a 'non-spiking' neurone: graded responses and spikes in the afferent P fibre of the crab thoracic-coxal muscle receptor organ. AB - The small diameter P neurone (7 microns) is here characterized as an afferent of the crab thoracic-coxal muscle receptor organ (TCMRO), in addition to the S and T neurones (50-60 microns). The P neurone employs both passively conducted, graded amplitude receptor potentials and, superimposed upon these, either graded active membrane responses or constant amplitude action potentials. Intracellularly recorded receptor potential waveforms reflect the dynamic component of stretch more strongly than receptor length, while action potentials at the onset of stretch accentuate the phasic response characteristics of this neurone. PMID- 2322832 TI - Hypothalamic neuronal activity responses to 3-hydroxybutyric acid, an endogenous organic acid. AB - To elucidate the anorectic action of the endogenous organic acid, 3 hydroxybutyric acid (3-HBA), its effects on neurons in both the rat ventromedial hypothalamic nucleus (VMH) and the lateral hypothalamic area (LHA) were examined. Iontophoretic application of 3-HBA significantly facilitated the firing rate of VMH neurons, whereas facilitation and inhibition were observed in the LHA. These responses were specific to the glucoreceptor neurons in the VMH and glucose sensitive neurons in the LHA. Intracellular recordings from brain slice preparations revealed that 3-HBA depolarized the cell membrane of the VMH neuron with an associated increase of membrane input resistance. This was similar to the effect of glucose on glucoreceptor neurons in the VMH. These results suggest that 3-HBA may modulate hypothalamic chemosensitive neuron activity as well as function as an endogenous satiety factor. PMID- 2322833 TI - A biphasic change of afterdischarge threshold during the kindling process. AB - Cats were stimulated in the ventral hippocampus with low-frequency (about 3 Hz) square wave pulses. All subjects were kindled until generalized convulsion occurred. During the kindling process, the number of stimulating pulses required for the provocation of afterdischarge (AD), which was used as an indicator of AD threshold, decreased suddenly in the initial stage and increased gradually in the late stage. We consider this phenomenon to be important in deepening the understanding of seizure generation. PMID- 2322834 TI - Glucose utilization in human visual cortex is abnormally elevated in blindness of early onset but decreased in blindness of late onset. AB - Glucose utilization has been studied in the visual cortex of blind human subjects, by comparison with normal volunteers, using positron emission tomography. In 6 subjects who became blind early in life ('early blindness'), metabolism in visual cortex was elevated, comparable to that of normal subjects studied with the eyes open. By contrast, glucose utilization in visual areas of 6 human subjects who became blind after completion of visual development ('late blindness') was decreased, slightly lower than in normal volunteers studied with the eyes closed. This unexpected difference between early and late blind subjects might reflect the persistence, in early blindness, of supranumerary synapses which would escape the normal developmental decrease in synaptic density during infancy. PMID- 2322835 TI - 5-HT3 receptors modulate spinal nociceptive reflexes. AB - The selective 5-HT3 receptor agonist 2-methyl-serotonin (2-Me-5-HT) mimicked the antinociceptive activity of 5-HT when intrathecally administered to rats. Two hundred micrograms (i.t.) doses of these agonists produced similar increases in tail flick latency. However, equal doses of 2-Me-5-HT and 5-HT doubled and tripled, respectively, the mean response latency as measured by the hot plate test. The potent and selective 5-HT3 receptor antagonists ICS 205-930 (3-tropanyl indole-3-carboxylate) and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) antagonized the antinociceptive effects of both 5-HT and 2-Me-5-HT. However, there were differences in the efficacy of these antagonists. Thus, intrathecal pretreatment with ICS 205-930 (0.05 micrograms) or MDL 72222 (0.1 micrograms) blocked the antinociceptive effects of 5-HT (200 micrograms, i.t.) as measured by the tail flick test, however, higher doses (0.1 and 1.0 micrograms, respectively) were required in the hot plate test. Pretreatment with ICS 205-930 (0.1 microgram) or MDL 72222 (0.1 microgram) blocked the effects of 2-Me-5-HT (200 micrograms, i.t.) in both analgesiometric tests. It is concluded that 5-HT3 receptors are intimately involved in the modulation of spinal nociceptive responses. PMID- 2322837 TI - Focal magnetic coil stimulation reveals motor cortical system reorganized in humans after traumatic quadriplegia. AB - A figure of '8' magnetic coil (MC) was used to stimulate focally the motor cortex of two adult, traumatic quadriplegics and three normal adults. The two patients were injured approximately 2 years previously and had intense physiotherapy, including biofeedback training of biceps and deltoid muscles, respectively, which were the most caudal muscles spared. The focal MC elicited compound motor action potentials (CMAPs) from these muscles from a much wider area of scalp than in the normal subjects. Latency of biceps and deltoid CMAPs were inversely related to CMAP amplitude. A reorganization of the motor cortical projection system is inferred, in which areas normally eliciting digit movements instead activate muscles in quadriplegics just above the spinal level. The reorganization applies also to the central sense of movement normally elicited by focal frontal cortex stimulation. Possible mechanisms of the reorganization and an implication for rehabilitation are discussed. PMID- 2322836 TI - Striosomal organization of cholinergic and dopaminergic uptake sites and cholinergic M1 receptors in the adult human striatum: a quantitative receptor autoradiographic study. AB - The distribution of cholinergic pre- and postsynaptic markers and dopaminergic presynaptic markers was analyzed in the adult human striatum, using quantitative receptor autoradiography. The distribution of the different binding sites indicates that cholinergic and dopaminergic uptake sites display a striosomal organization, with a higher binding site density in the striatal matrix. M1 muscarinic cholinergic receptor distribution parallels the distribution of cholinergic presynaptic markers. Our data show that cholinergic and dopaminergic terminals, and M1 receptors are enriched in the matrix of the adult human striatum. PMID- 2322838 TI - Patterns of change in endoneurial capillary permeability and vascular space during nerve regeneration. AB - In frog sciatic nerve crushed and allowed to regenerate, an in situ perfusion technique was used to measure the permeability coefficient-surface area product (PS) of endoneurial capillaries to [14C]sucrose and endoneurial vascular space (V) at intervals of 3 days to 12 weeks post-crush. Additionally, the amplitude and latency of the compound action potential (CAP) of the regenerating nerve were also monitored. There was a delayed increase of both PS and V which peaked at 2-3 weeks after the crush and then declined. This is strikingly similar to the pattern seen in transected nerves. Whereas both PS and V reached near normal levels 6 weeks after transection, in regenerating nerves V continued toward normal levels but PS increased again to peak around 9 weeks post-crush. This second peak of PS coincided with a rapid increase of the CAP amplitude and a sharp decline of its latency. As is the case for transected nerves, the initial increase of PS is probably induced by breakdown products of axons or chemical signals from attendant Schwann cells and related to the clearance of debris from the endoneurium. The later increase of PS may be an endoneurial homeostatic mechanism to increase blood-nerve exchange during rapid axonal growth and remyelination. PMID- 2322839 TI - A deficiency of axonal regeneration in C57BL/6J mice. AB - Axonal regeneration within peripheral nerves and dorsal spinal roots was investigated in inbred strains of mice with known differences in macrophage recruitment and inflammatory functions. During the second week after sciatic nerve crush, counts of regenerating newly myelinated fibres were significantly lower in C57BL/6J mice than in 4 other strains. After dorsal root crush with or without concomitant sciatic nerve transection to enhance regeneration, fibre counts in roots of C57BL/6J were one-fifth of those in A/J mice. Axonal regeneration is subnormal in C57BL/6J mice but this defect appears not to be linked to known deficiencies in macrophage function. PMID- 2322841 TI - Atrophy of the ipsilateral substantia nigra following middle cerebral artery occlusion in the rat. AB - Following occlusion of the left middle cerebral artery in the rat, marked atrophy was observed in the ipsilateral substantia nigra in and after the second week. The mechanism of this neuropathological change in the substantia nigra, which is remote from the site of infarction, may be explained by transsynaptic, neurotransmitter-mediated disinhibition as a result of infarction of the striatum. PMID- 2322840 TI - Age-related cholinergic drug effects on analgesia in two inbred strains of mice. AB - The two inbred strains of mice C57BL/6 and DBA/2 are characterized by a different behavioral reactivity to cholinergic agents during development. The present experiment revealed that the strain-dependent differences in cholinergic-mediated analgesia during development disappeared during adult life. In fact, oxotremorine administration (0.0025 and 0.005 mg/kg) exerted the same analgesic effect in both strains at 6 months of age, in contrast with the finding of the lack of any effect of the drug in C57 mice at two months of age in comparison with DBA. PMID- 2322842 TI - Chronic maintenance of presynaptic terminals in gliotic hippocampus following ischemia. AB - Following brief cerebral ischemia, neurons are selectively damaged and die, whereas glial cells and blood vessels survive. This phenomenon of selective vulnerability is well illustrated in the hippocampal CA1 region. Five min of forebrain ischemia in the Mongolian gerbil produced selective neuronal necrosis in the hippocampal CA1 sector. After destruction and loss of CA1 neurons, a remarkable glial reaction (gliosis) was seen. The thickness of the CA1 subfield remained unchanged until 1 month after ischemia and then gradually shrank over several months. Ultrastructural observation of this region revealed persistent maintenance of presynaptic structures. Numerous presynaptic terminals containing synaptic vesicles were scattered throughout the gliotic scar tissue. These presynaptic terminals were apposed to degenerative structures which seemed most likely to be remnants of dendrites. In another group of animals, at one month following ischemic damage in the CA1 sector, the CA3 neurons were destroyed by kainic acid injection. In these animals, numerous degenerating presynaptic boutons were seen in the CA1 sector when fixed 4 days following kainate injection. These results indicate that even in gliotic tissue, presynaptic terminals can survive and maintain their structural characteristics although neuronal cell bodies are almost absent. PMID- 2322843 TI - The effect of delta sleep-inducing peptide (DSIP) and phosphorylated DSIP (P DSIP) on the apomorphine-induced hypothermia in rats. AB - Delta sleep-inducing peptide (DSIP) and P-DSIP, phosphorylated analogue, were found to have enhancing effects on hypothermia induced by i.p. injection of apomorphine (2 mg/kg), a dopamine agonist. Further, the action of P-DSIP appeared and diminished more quickly than that of DSIP. A minimal effective dose of these peptides was 10 ng and the dose-response relationship exhibited an inverted bell shape with a maximal effective dose of 1 microgram. By the pretreatment of anti DSIP the enhancing effect of DSIP but not P-DSIP, was totally abolished and the action of both peptides was antagonized by haloperidol. These findings suggest that DSIP and P-DSIP have a close relation to the dopaminergic system on the thermoregulatory mechanisms. PMID- 2322844 TI - Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2 alpha to conscious mice. AB - The effects of intrathecal administration of prostaglandins on pain responses in conscious mice were evaluated by using hot plate and acetic acid writhing tests. Prostaglandin D2 (0.5-3 ng/mouse) had a hyperalgesic action on the response to a hot plate during a 3-60 min period after injection. Prostaglandin E2 showed a hyperalgesic effect at doses of 1 pg to 10 ng/mouse, but the effect lasted shorter (3-30 min) than that of prostaglandin D2. Similar results were obtained by acetic acid writhing tests. The hyperalgesic effect of prostaglandin D2 was blocked by simultaneous injection of a substance P antagonist (greater than or equal to 100 ng) but not by AH6809, a prostanoid EP1-receptor antagonist. Conversely, prostaglandin E2-induced hyperalgesia was blocked by AH6809 (greater than or equal to 500 ng) but not by the substance P antagonist. Prostaglandin F2 alpha had little effect on pain responses. These results demonstrate that both prostaglandin D2 and prostaglandin E2 exert hyperalgesia in the spinal cord, but in different ways. PMID- 2322845 TI - The reserpine-sensitive dopamine pool mediates (+)-amphetamine-conditioned reward in the place preference paradigm. AB - The neural basis of amphetamine-conditioned reward was investigated in the conditioned place preference paradigm. When bilaterally injected into the nucleus accumbens before the test session, a dopamine receptor blocker, alpha flupenthixol, blocked the expression of the amphetamine-conditioned place preference. alpha-Flupenthixol had no significant effect on spontaneous locomotor activity. Bilateral microinjections of a tyrosine hydroxylase inhibitor, alpha methyl-p-tyrosine (alpha-MPT), decreased (+)-amphetamine locomotor stimulation in a dose-dependent fashion. Two doses of alpha-MPT that completely blocked (+) amphetamine locomotor stimulation had no effect on the expression of the conditioned place preference when injected into the nucleus accumbens before testing. Reserpine administered subcutaneously before testing blocked the expression of the conditioned place preference. A dose of reserpine (4.0 mg/kg), which completely blocked the conditioned place preference, did not attenuate (+) amphetamine-induced locomotor stimulation. This dose of reserpine depleted dopamine in the nucleus accumbens to 4% of its normal value. These data show that (+)-amphetamine-conditioned reward, expressed as a conditioned place preference, is mediated by dopamine release in the nucleus accumbens. Moreover, the dopamine is released from the reserpine sensitive pool, and probably not from the newly synthesized alpha-MPT-sensitive pool. PMID- 2322846 TI - Electrophysiological properties of reactive glial cells in the kainate-lesioned hippocampal slice. AB - Kainate-lesioned hippocampal slices provide an excellent system for examining the electrophysiological properties of non-cultured glial cells without interfering signals from surrounding neurons. Intracellular recordings in the intensely gliotic CA3 region indicated that the resting membrane potential and input resistance of these reactive glial cells were similar to those reported for non reactive astrocytes. Dye-coupling typical of astrocytes was also demonstrated amongst these cells, and was considerably reduced by cytoplasmic acidification. Occasionally these cells demonstrated spontaneous, rhythmic oscillations of membrane potential associated with large changes in whole cell input resistance. The action potentials reported in cultured astrocytes were not observed in reactive glial cells, even under conditions that maximize the observation of Ca2(+)-dependent responses. This suggests that reactive glial cells in this preparation have either no voltage-activated Ca2+ channels or a very low density of such channels. These cells also lack a bicarbonate conductance, but they do appear to have an apamin-sensitive conductance, possibly a Ca2(+)-activated gK. PMID- 2322847 TI - Distribution of ectopic neurite growth and other geometrical distortions of CNS neurons in feline GM2 gangliosidosis. AB - Golgi and combined Golgi-electron microscopic (EM) studies were carried out on cats in the terminal stages of GM2 ganglioside storage disease and the resulting data were compared with those from similar studies of other neuronal storage diseases in cats, including GM1 gangliosidosis. The results support the view that only limited types of neurons affected by the lysosomal hydrolase deficiency and subsequent intracellular storage have the capacity to sprout new dendritic-like growth processes from their axon hillocks, and that these neurons are essentially the same in all of these diseases studied to date. Golgi studies of CNS tissues from GM2 gangliosidosis cats revealed ectopic neurite growth on pyramidal neurons of cerebral cortex and multipolar cells of amygdala and claustrum, whereas other types of neurons responded to the metabolic defect with aspiny meganeurite formation or somatic enlargement, or appeared normal in terms of soma-dendritic morphology. Combined Golgi-EM studies of cortical pyramidal neurons revealed that ectopic, axon hillock neurites commonly possessed asymmetrical synapses which were similar to those observed in other storage disorders. PMID- 2322848 TI - Opposite dopaminergic activity in lateral and median hypothalamic nuclei in relation to the feeding effect of D-Ser2-Leu-Enk-Thr6 (DSLET). AB - The Leu-enkephalin analogue D-Ser2-Leu-Enk-Thr6 (DSLET) had been shown to enhance feeding in rats, increase dopaminergic activity in the striatum like other opiate agonists, and particularly to decrease dopaminergic activity in the hypothalamus. In this study, the latter effect was found to be localized in the hypothalamic nuclei involved in the regulation of feeding such as the paraventricular (PVN), ventromedian (VMH), dorsomedian (DMH) nuclei and the lateral hypothalamus (LH). DSLET produced the same decrease in dopaminergic activity in the LH as in the whole hypothalamus. In the median nuclei (PVN and VMH and to a lesser extent in the DMH), an opposite effect was observed, resembling that in the striatum. The relevance of these opposite variations with regard to the feeding effect of DSLET is discussed. The decreased dopaminergic activity in the LH would appear to be the most specifically related to the behavioural effect given the known role of dopamine in this region. These data reconcile apparently contradictory aspects of the role of dopamine and the functional opposition between the lateral and median hypothalamus in food intake control. PMID- 2322849 TI - Postischemic glucose utilization in rat hippocampal layers. AB - The influence on hippocampal glucose utilization was determined in male Wistar rats 7 days after a 10-min forebrain ischemia. Ischemia was induced by clamping of the carotid arteries and lowering blood pressure to 40 mm Hg. Despite severe neuronal damage as assessed by histological techniques, local cerebral glucose utilization (LCGU) was significantly increased in the pyramidal and radiatum layer of the CA1 sector, while in layers of the CA2, CA3 and CA4 sector and dentate gyrus. LCGU was reduced compared to non-ischemic controls. The increases in LCGU are suggested to reflect long-lasting hyperexcitation in the selectively vulnerable CA1 sector, implicating a correlation between cellular hypermetabolism and neuronal damage. PMID- 2322850 TI - The effect of acetylcholine on rat olfactory bulb unit activity. AB - The olfactory bulb (OB) of the rat receives an extrinsic innervation from the most anterior part of the basal forebrain cholinergic complex. The effect of microiontophoretically applied acetylcholine (ACh) on OB unit activity was studied in 16 adult male rats. A total of 80 units was recorded and in 50% of the cases the cell layer where the recording was done was clearly identified. The results provide evidence for a particularly high level of sensitivity to ACh in the outer glomerular layer (73%). Both inhibitory and excitatory responses were found. These results are in agreement with histological studies indicating that this layer presents the highest density of cholinergic terminals. As a whole, present knowledge suggests the existence of a strong cholinergic control of the olfactory input at the level of the first synapse in the system. PMID- 2322852 TI - Photoperiodic responsiveness of hamsters with lesions of the lateral geniculate nucleus is related to hippocampal damage. AB - We tested the hypothesis that the geniculohypothalamic tract is important for hamster photoperiodism. Adult male hamsters, maintained in a long photoperiod (LD 14:10), received either large bilateral neurotoxic lesions of the lateral geniculate nucleus (LGN) or sham lesions. One week later, half of the animals from each group were transferred to a short photoperiod (LD 8:16) where they were maintained for 15 weeks. Most lesions effectively destroyed the intergeniculate leaflet (IGL) and much of the lateral geniculate complex. They also caused substantial damage to the overlying hippocampus. The lesions had no effect on long-day animals, but significantly reduced the extent of testicular regression during short photoperiod exposure. This effect, however, appeared to be the result of hippocampal, rather than geniculate, damage. Four individuals with complete IGL lesions, but minimal hippocampal damage, underwent a pattern of regression that was indistinguishable from controls. Body weight was increased by lesions in short-day, but not long-day, animals. This effect was not related to the extent of hippocampal damage. We conclude that geniculate input to the suprachiasmatic nuclei is not essential for hamster photoperiodism and that hippocampal damage may modify the effect of short daylengths on testes size. PMID- 2322851 TI - Hemicholinium-3 binding sites in subnuclei of the rat interpeduncular nucleus: quantitative in vitro autoradiography. AB - The interpeduncular nucleus (IPN) receives dense cholinergic input from the medial habenulae (MH) via the fasciculus retroflexus (FR). This projection is known to terminate in the rostral, central and intermediate subnuclei. Correspondingly, the concentration of hemicholinium-3 (HC-3) binding sites in these subnuclei was equal to or greater than that reported in any other brain areas. Moderate values in the distal FR and in the lateral subnuclei indicate that choline uptake sites are located on nonterminal portions of MH afferent axons as well. Possible relationships of HC-3 binding to the unusual metabolic properties of FR and IPN, and to the distribution of choline acetyltransferase containing axons and terminals in FR and IPN are suggested. PMID- 2322853 TI - Afferent connections of the rat's supraoptic nucleus. AB - Neurons projecting to the supraoptic nucleus (SON) have been identified following stereotaxic injections of either horseradish peroxidase or fast blue into the SON region of adult rats. The subfornical organ, median preoptic nucleus, organum vasculosum of the lamina terminalis and medial septal nucleus were the source of the largest numbers of supraoptic-projecting neurons. Several smaller projections also originate from the ipsilateral locus coeruleus, preoptic area, lateral parolfactorial area, dorsomedial nucleus of the hypothalamus, lateral parabrachial nucleus and ventrolateral medulla. Several other areas appeared to project only to the region immediately dorsal to the SON: lateral septal nucleus, diagonal band of Broca, ventral tegmental nucleus, and the supramamillary nucleus. These areas may influence SON neurosecretory function by way of interneurons found immediately dorsal to SON. Additional areas were identified with retrograde fluorescent label only, and these projected to the area immediately dorsal to SON and/or to SON itself. PMID- 2322854 TI - Effects of prenatal exposure to cocaine or related drugs on rat developmental and neurological indices. AB - Although increasing numbers of infants born to cocaine abusing mothers are of grave concern, little is known of the long term development of these children. To determine the long term effects of cocaine on a developing fetus, gravid rats were dosed SC throughout pregnancy with either saline, amfonelic acid (AFA, 1.5 mg/kg), amitriptyline (10 mg/kg) or cocaine (15 mg/kg b.i.d.) and the male pups fostered by surrogate rats. Compared to saline offspring, cocaine- and amitriptyline-exposed litters were underweight at birth, but there were no differences between groups at 15 or 30 days of age. There were more birth defects and stillbirths in cocaine-exposed offspring, however, there were no differences in male/female sex ratios or litter size in any group. Number of days to righting reflex was delayed in the cocaine-exposed group, but there were no changes in time to eye opening. Cocaine- and amitriptyline-exposed pups were hyperactive at 30 days of age, though no differences were found in an initial 15-min exploration period. Only the AFA-exposed offspring were hyperactive at 60 days postnatal. Since cocaine and amitriptyline decreased birth weights, this effect may be related to the nondopaminergic effects of cocaine. These data demonstrate that cocaine exposure in utero at relevant doses can affect neonatal outcome and long term development in rat offspring. PMID- 2322855 TI - The influence of striatum on the substantia nigra: a study using the spreading depression technique. AB - Effects of changes in striatal neurone activity on substantia nigra (SN) unit activity were studied in rats. Striatal changes were produced by the spreading depression (STSD) induced by perfusing the head of striatum with 0.06 M KCl via a push-pull cannula. In the medial part (caudate) striatal neurones are silent, with the arrival of STSD they exhibit a brief excitation coinciding with the onset of a slow wave of depolarisation in the extracellular steady potential. In the lateral part (putamen) striatal neurones are active, they undergo an arrest of their spontaneous activity for about 1 minute following the brief excitation. Antidromic activation of SN reticulata (SNr) neurones was attempted from the superior colliculus (SC). The majority of the 54 SNr neurones (96%) exhibited changes in firing rate during STSD. Ten neurones underwent brief single or repetitive changes of the same duration as the brief striatal excitation. Eight presented an initial brief change of activity followed by a longer duration inverse change in firing rate. Eighteen exhibited multiple brief changes followed by or superimposed on a long lasting decrease of firing rate and 50% of them were nigrotectal neurones. Sixteen neurones presented long duration biphasic changes in firing rate. Two SNr neurones and the 12 substantia nigra compacta (SNc) neurones studied were unaffected. Some neurones received both inhibitory and facilitatory striatal controls. In total thirty-nine neurones were inhibited and 47 facilitated, the origin of these effects from caudate and putamen are discussed. The excitatory action may be due to either a direct excitatory pathway or to a relayed effect of the inhibitory GABAergic pathway. PMID- 2322856 TI - Projections of two separate cortical areas for rhythmical jaw movements in the rat. AB - The cortico-bulbar projection from two separate cortical areas which induce different types of rhythmical jaw movements (RJM), and the relationship between these cortical areas were studied with horseradish peroxidase tracing method. One area (A-area) corresponded to the primary jaw motor area and the other (P-area) was located in the agranular insular cortex. Separate descending pathways from two areas passed through the pyramidal tract and projected to the supratrigeminal nucleus, the intertrigeminal region, the dorsal part of the trigeminal sensory complex, and the reticular formation. In the reticular formation, the A-area projected more medially than the P-area did, and the ipsilateral projection from the P-area was more prominent than that from the A-area, although contralateral projections were dominant in the majority of regions. The two areas had only a sparse reciprocal connection. We suppose that the difference in patterns of RJM induced by the two cortical RJM areas may be due to the different projection patterns from these two areas. PMID- 2322857 TI - Collateral input to the paraventricular and supraoptic nuclei in rat. I. Afferents from the subfornical organ and the anteroventral third ventricle region. AB - Injections of two fluorescent retrograde tracers were used to investigate the existence of collateral branching of input to the hypothalamic magnocellular neuroendocrine neurons. Injection of one tracer (either Fluoro-Gold or rhodamine labeled microspheres) into the supraoptic nucleus and the other tracer into the ipsilateral paraventricular nucleus produced labeled neurons within the subfornical organ and the anteroventral third ventricle area. Some labeled cells were found to contain both fluorescent tracers (double-labeled cells), suggesting that they project to both the paraventricular and supraoptic nuclei via branching axons. Most double-labeled cells were found within the subfornical organ. Fewer of these cells were located within the nucleus medianus preopticus, and still fewer were distributed in the organum vasculosum lamina terminalis, the bed nucleus of the stria terminalis, and the medial and the lateral preoptic areas. These data present the first direct evidence that single cells may provide input to more than one magnocellular neuroendocrine nucleus. Hypothetically, hormonal release would require coordinated firing of many magnocellular cells. Thus, the branched input to these neurons may assist in the organization and the timely activation of this system in response to physiological stimuli. PMID- 2322858 TI - Murine strain differences in taste responsivity and organization of the rostral nucleus of the solitary tract. AB - Taste responsivity and organization of fungiform papillae, geniculate ganglion neurons and gustatory recipient zones of the nucleus of the solitary tract (NST) were examined in C57BL/6NCrlBR (C57) mice, BALB/c6NCrlBR (BALB/c) mice and CB6F1/CrlBr (CB6) mice, an F1 hybrid cross between BALB/c and C57 mice. Results from behavioral studies confirm that C57 and CB6 mice exhibit higher preferences to sucrose and lower preferences to NaCl, as compared to BALB/c mice. No strain differences were confirmed for aversion responses to citric acid or quinine HCl taste stimuli. Anatomical analyses show that the number and organization of fungiform papillae do not reliably differ between C57, BALB/c, and CB6 mice, nor do volumes of glossopharyngeal terminal fields in the NST. However, strain specific differences exist in the number of neurons contained in the geniculate ganglion, volume of chorda tympani (CT) terminal fields in the rostral NST, and number of NST neurons contained in CT terminal fields. BALB/c and CB6 mice possess a greater number of geniculate ganglion neurons and larger CT terminal fields, as compared to C57 mice. However, strain differences in the number of geniculate ganglion neurons and terminal field volume are not obviously correlated with strain differences in gustatory responsivity. The only reliable relationship confirmed between taste responsivity and neuroanatomical organization of the rostral NST relates to the absolute number of neurons contained in CT terminal fields, and corresponding neuronal density within CT terminal fields. Chorda tympani terminal fields of C57 and CB6 mice contain an average of 379 neurons, whereas CT terminal fields of BALB/c mice contain an average of 531 neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322859 TI - Regional changes in brain 14C-2-deoxyglucose uptake after feeding-inducing intrahypothalamic norepinephrine injections. AB - Although norepinephrine (NE) injections into the paraventricular hypothalamus (PVN) have been extensively documented to induce feeding in satiated rats, there have been few systematic attempts to elucidate the neural circuitry subserving this response. In this study quantitative 14C-2-deoxyglucose (14C-2DG) autoradiography was used to map regional brain changes induced by PVN NE injections. Male Wistar rats, bearing PVN cannulae and previously shown to be positive responders for NE-induced feeding, were given 125 microCi/kg 14C-2DG IV immediately following a PVN injection of either 40 nmol NE or vehicle, then killed 45 min later. 14C-2DG uptake was examined in 97 brain structures using computerized densitometry. PVN NE injections resulted in small, localized changes in brain 14C-2DG uptake. Forebrain structures affected included the somatosensory parietal cortex (+15%), the CA3 hippocampal field (-8%), and the reticular thalamic nucleus (+14%). Midbrain changes involved the anterior pretectal area (+8%) and the central gray area (-11%). At the hindbrain level, the lateral reticular nucleus showed the most pronounced changes of all brain regions examined (-24%), followed by the nucleus of the solitary tract (-16%) and the laterodorsal tegmental nucleus (+16%). No changes were seen in the median eminence or in other hypothalamic areas. This pattern of results largely agrees with recent proposals for the circuitry of a PVN-hindbrain system subserving NE induced as well as hypothalamic lesion-induced feeding effects. In addition, however, they suggest the possibility that altered activity in some forebrain structures may also be involved in the NE response. PMID- 2322860 TI - Mapping the effects of motor cortex stimulation on somatosensory relay neurons in the rat thalamus: direct responses and afferent modulation. AB - Single unit recordings were used to map the spatial distribution of motor (MI) cortical influences on thalamic somatosensory relay nuclei in the rat. A total of 215 microelectrode penetrations were made to record single neurons in tracks through the medial and lateral ventroposterior (VPM and VPL), ventrolateral (VL), reticular (nRt), and posterior (Po) thalamic nuclei. Single units were classified according to their: 1) location within the nuclei, 2) receptive fields, and 3) response to standardized microstimulation in deep layers of the forepaw-forelimb areas of MI cortex. For mapping purposes, only short latency (1-7 msec) excitatory neuronal responses to the MI cortex stimulation were considered. Percentages of recorded thalamic neurons responsive to the MI stimulation varied considerably across nuclei: VL: 42.6%, nRt: 23.0%, VPL: 15.7%, VPM: 9.3%, and Po: 3.9%. Within the VPL, most responsive neurons were found in "border" regions, i.e., areas adjacent to the VL, and (to a lesser extent) the nRt and Po thalamic nuclei. The same parameters of MI cortical stimulation were used in studies of corticofugal modulation of afferent transmission through the VPL thalamus. A condition-test (C-T) paradigm was implemented in which the cortical stimulation (C) was delivered at a range of time intervals before test (T) mechanical vibratory stimulation was applied to digit No. 4 of the contralateral forepaw. The time course of MI cortical effects was analyzed by measuring the averaged evoked unit responses of the thalamic neurons to the T stimuli, and plotting them as a function of C-T intervals from 5-50 msec. Of the 30 VPL neurons tested during MI stimulation, the average response to T stimulation was decreased a mean 43%, with the suppression peaking at about 30 msec after the C stimulus. This suppression was more pronounced in the VPL border areas (-52% in areas adjacent to VL and nRt) than in the VPL center (-25%). PMID- 2322861 TI - Cocaine enhances medial prefrontal cortex neuron response to ventral tegmental area activation. AB - Extracellular single unit recording techniques were used to characterize the effect of cocaine on the response of identified medial prefrontal cortex (mPFC) neurons to electrical stimulation of the ventral tegmental area (VTA) in chloral hydrate anesthetized rats. The select population of neurons studied were identified as cortical efferent cells by action potential characteristics and antidromic activation from the VTA. Stimulation of the VTA also induced a synaptically mediated inhibition of the spontaneous activity of the mPFC neurons. Administration of 2.0 mg/kg cocaine (IV) produced an increase in the duration of the VTA stimulus-evoked inhibition that differed significantly from the effect of 4.0 mg/kg procaine (IV). In contrast, microiontophoretic cocaine and procaine produced no significant changes in the duration of the VTA stimulus-evoked inhibition. This study provides evidence that systemic but not microiontophoretic cocaine administration enhances dopamine receptor-mediated inhibitory VTA input to a select population of mPFC efferent neurons. PMID- 2322862 TI - Angiotensin II and angiotensin (1-7) excite neurons in the canine medulla in vitro. AB - Our group showed previously that the heptapeptide angiotensin (1-7) [Ang-(1-7)] is a bioactive product of the renin-angiotensin system, and produces dose dependent cardiovascular effects similar to those evoked by Ang II when microinjected into the nucleus tractus solitarii (nTS) of the rat. The effects of Ang II were compared with those of Ang-(1-7) on single neuron activity recorded from the medial nTS or dorsal motor nucleus of the vagus (dmnX) in perifused horizontal slices of the canine dorsomedial medulla. Ang II excited 48% of 31 medial nTS neurons, but only activated 14% of 22 dmnX cells. Ang-(1-7) also excited half of the medial nTS cells and 14% of the dmnXl neurons. Although most medial nTS neurons excited by Ang II were also activated by Ang-(1-7), two cells were excited by Ang II but not by Ang-(1-7), and one cell was excited by Ang-(1 7) but not by Ang II. Because Ang-(1-7) lacks direct vasoconstrictor effects, neurons in the dorsomedial medulla may have different receptor characteristics than peripheral tissues. The observation of a few medial nTS neurons excited by only one Ang peptide suggests that there may be a separate Ang-(1-7) receptor that participates in the physiological effects of Ang peptides mediated by the brain. PMID- 2322863 TI - Alterations in cytosolic free calcium in the cat cortex during bicuculline induced epilepsy. AB - Influx of calcium ion (Ca++) into the neurons has recently been implicated in the generation of seizure activity. Utilizing indo-1, a fluorescent Ca++ indicator, changes in cytosolic free calcium ([Ca++]i), NAD/NADH redox state and hemodynamics were simultaneously measured in vivo from the cat cortex during bicuculline-induced seizure activity. A ratio of indo-1-Ca++ fluorescence at 400 and 506 nm during ultraviolet excitation (340 nm) was utilized as a measure of changes in [Ca++]i. Alterations in the NAD/NADH redox state and local cortical blood volume (1CBV) were assessed at 464 nm and 340 nm, respectively. Local cortical blood flow (1CBF) was calculated from 1CBV and mean transit time determined from cortical hemodilution curves. Electroencephalogram (EEG) was monitored from the same cortical region as the optical measurements. The [Ca++]i signal ratio started to increase 19 +/- 2 sec prior to the onset of seizure activity on the EEG and remained elevated until the activity was suppressed by an intravenous administration of diazepam (2 mg/kg). The early increase in [Ca++]i is presumably due to a synaptic Ca++ entry associated with facilitated excitatory neurotransmission. The NAD/NADH redox state became oxidized during the seizure activity and started to recover as the EEG activity was suppressed. The 1CBV and 1CBF increased by 17 +/- 8% and 68 +/- 16%, respectively, 10 min into the seizure activity. This study provides direct in vivo evidence suggesting a possible role of calcium entry into the neurons in the epileptogenesis. PMID- 2322864 TI - Neuropeptide Y in the specific hypothalamic nuclei of rats treated neonatally with monosodium glutamate. AB - Neuropeptide Y (NPY) concentration was determined by radioimmunoassay in selected hypothalamic regions microdissected from fresh brain slices of rats treated neonatally with monosodium glutamate (MSG). Fourteen weeks after MSG treatment, significant decreases in NPY concentration were found in the paraventricular nucleus (PVN) and arcuate nucleus (ARH), while there was no appreciable change in the ventromedial nucleus (VMH) and lateral area (LH). The decrease in NPY in the ARH-PVN system may contribute to the endocrine and metabolic disturbances seen in MSG-treated animals. PMID- 2322865 TI - [The effect of nitrofuran and asymmetrically substituted urea on Trichomonas vaginalis and Tritrichomonas foetus in vitro and in vivo]. AB - Antitrichomonal activity of selected nitrofuran derivatives and asymmetrically substituted ureas was investigated in vitro and in vivo and compared with the activity of the effective therapeutic agent tinidazole. In experimental infection with Trichomonas vaginalis and Tritrichomonas foetus in mice, some substituted urea derivatives exhibited an antiparasitic effect slightly lower than that of tinidazole. The substance N1-(3-nitrophenyl)-N3-(2-pyrimidinyl)urea proved to be the most effective of the substances tested. On the basis of preliminary toxicity tests the chemotherapeutic value of this substance appears to be promising. PMID- 2322866 TI - [Analysis of screening questionnaires for differences in alcoholism between men and women]. AB - The results of the Alcohol Dependence Scale (ADS) and the Michigan Alcoholism Screening Test (MAST) obtained in a series of male and female outpatients and inpatients treated for alcoholism are analyzed. Factor analysis of ADS and MAST in men and women showed different arrangement of factors for each sex. The paper presents the results of a pilot study with a preliminary version of the original Female Alcoholism (FeA) screening. PMID- 2322867 TI - Central nervous complications in subjects with artificial heart. AB - The artificial heart is a device for urgent solution of final heart failure. The systems used currently for this task are particularly pneumatic systems that allow only a limited life comfort for the patient. Therefore they have been used for short-term application as so-called bridge systems designed for periods preceding heart transplantation. Artificial hearts should be available for such situations. They are antithrombogenic owing to their construction and material properties and thus the patient's central nervous system is not threatened by thromboembolic complications. The Czechoslovak artificial heart TNS-Brno-VII is optimal in this respect. In experiments lasting for months, however, microembolism into the CNS from a calcified diaphragm often threatens the experimental animal. This danger can be limited both by optimal construction of the pump and by affecting the calcifying mechanism biologically, or by suitable processing of the diaphragm material that prevents calcifying nucleation. Perfect technology in the production of artificial hearts warrants complete elimination of potential air embolism into the central nervous system. Therefore the aim of further research is to design an absolutely defect-free system of the artificial heart which would eliminate any damage to the central nervous system during permanent long-lasting application, either on the basis of cerebral embolism of any origin, or on the basis of CNS hypoperfusion caused by limited pumping function of the artificial heart. PMID- 2322868 TI - [Carcinoma of the oral cavity--analysis of local metastases and results of therapy]. AB - A series of 453 patients admitted to the 2nd Clinic of Stomatology in Bratislava over the ten-year period from 1977-1986 was statistically evaluated. The series comprised patients with the diagnosis of epidermoid carcinoma of the oral cavity, with the exception of carcinoma of the lip. The condition of the regional lymphatic apparatus at the first examination and over the succeeding period was studied. The relationship between the treatment used, clinical stage and prognosis of tumorous disease in the orofacial region was evaluated. The possibilities of different types of cervical dissection are discussed along with the histological findings recorded. In the light of the survival period a direct relationship between the clinical stage of the disease at the onset of treatment and prognosis has been confirmed. PMID- 2322869 TI - [Electrical and electromagnetic stimulation of bone healing]. AB - The presented review analyzes the problem of the effect of electric current and electromagnetic fields on bone healing. The findings of the cited papers indicate that electronegativity, osteoblastic activity and bone formation fall within one group, while electropositivity, osteoclasia and resorption constitute another group. Stimulation is performed surgically by implanted electrodes or by current induction in the bone. Evidence on the effect of direct electric stimulation and pulsed magnetic filds in speeding up the process of bone healing fails to be convincing. However, the beneficial influence of electromagnetotherapy on the healing of soft tissues has been confirmed and is to be ascribed t its antiedematous, analgesic and antiinflammatory effect. PMID- 2322870 TI - [Present possibilities and perspectives in genetic toxicology]. AB - Information on the new branch of medical genetics--genotoxicology--is presented. The results obtained so far in the field of genotoxicologic research are briefly reviewed and the contribution of our departments is outlined. The conclusion indicates further trends in basic and applied research and emphasizes the necessity to take advantage of the knowledge and information achieved in genotoxicologic research in social practice. PMID- 2322871 TI - [Blood cholesterol levels and mortality in cancer]. AB - Prospective studies carried out in different parts of the world, with the most extensive one comprising 360,00 American men followed up over a period of 7-8 years, have found that the total serum cholesterol level correlates inversely with subsequent mortality for cancer. On excluding the first years following the determination of cholesterol level this inverse relationship decreases or disappears completely. The cholesterol level keeps decreasing for at least two years prior to death caused by cancer. Patients suffering from a malignant process are frequently found to have very low cholesterol levels and that even when they are in a good nutritional condition. The effect of the preclinical stage of cancer on the metabolism of plasma lipoproteins is presumed to account for the inverse correlation observed between cholesterol level and cancer. The rapidly multiplying cancer cells require great amounts of cholesterol to build up their new membranes and therefore increase the activity of receptors binding plasma low-density lipoproteins (LDL). This mechanism speeds up the transfer of plasma cholesterol into cancer cells. According to some reports increased cholesterol supply by food enhances the risk of cancer both in humans and experimental animals. Changes in the nutritional pattern aimed at preventing ischemic heart disease (reduced intake of satured animal fat and cholesterol) may be associated with a lower risk for malignancy. PMID- 2322872 TI - Leukocyte surface markers in Rana catesbeiana, identified using mouse monoclonal antibodies. AB - Monoclonal antibodies (mAbs), each reactive with thymocytes, neutrophils, and thrombocytes of the bullfrog, Rana catesbeiana, were raised and used for studies of hematopoiesis of metamorphic larvae. The mAbRc-T1, which immunoreacted exclusively with thymocytes in adults, was also strongly reactive to larval thymocytes. Thus the determinant Rc-T1 may provide an appropriate marker for thymocytes, although antigenic sharing is also seen in larval ovarian tissue. Neutrophils detectable by both mAbRc-N1 and Rc-N2 originated primarily in the mesonephros and showed up increasingly in peripheral blood of larvae. Thrombocytes detectable by mAbRc-P may originate in the larval spleen and/or liver but not in the mesonephros. PMID- 2322873 TI - Uncoupling of muscle-specific protein expression in myocyte x myoblast heterokaryons. AB - The inducibility of several rat skeletal muscle proteins was examined in heterokaryons formed by fusing differentiated chick myocytes to undifferentiated rat myoblasts. Chicken and rat proteins were distinguished using species-specific antibodies or by their different migrations in polyacrylamide or agarose gels. Both rat skeletal myosin light chain 1 and rat alpha-tropomyosin were induced in the heterokaryons. In contrast, neither rat acetylcholine receptors nor creatine kinase could be detected. These results suggest that chick myocytes may contain quantities of regulatory factors that are sufficient for the activation of some but not all of these rat muscle-specific proteins within the cellular context of the heterokaryon. PMID- 2322874 TI - Electroporation as a new technique for producing transgenic fish. AB - A recombinant plasmid, pMV-GH, containing rainbow trout growth hormone cDNA fused to mouse metallothionein I promoter, was introduced into medaka (Oryzias latipes) by electroporation. Of 3109 fertilized eggs treated with electric pulses (750 V/cm, 50 microseconds, 5 times), 783 (25%) hatched out. Four percent of the hatchlings were transgenic. To obtain transgenic lines, 180 hatchlings were maintained and 35 of them grew into adult fish. Two of these fish were transgenic. When one transgenic fish was mated with a normal female, the transgene was found in all the F1 offspring assayed. In F2 offspring obtained by mating transgenic F1 fish, 88% were transgenic. PMID- 2322875 TI - Regulation of oocyte number during oocyte differentiation in the lizard Podarcis sicula. AB - This paper concerns the differentiation process of germ cells from oogonia to primary follicles in the lizard Podarcis sicula. The study was carried out at the morphological level and using a cytophotometric analysis for determining the number of differentiating germ cells undergoing degeneration. The progressive disorganization of the germ cell clusters during the early diplotene stage and the role played by the prefollicular cells during this process are described. Oocyte degeneration has been observed between the mid-zygotene and the early diplotene stages. When the primary follicle (oocyte plus follicular cells) is being formed, the degeneration process stops and the oocyte undergoes regular growth and ovulation. PMID- 2322876 TI - One nurse's inspiring work touches many lives. PMID- 2322877 TI - CNA joins campaign for alcohol tax initiative. PMID- 2322878 TI - Medial extent of the posterior renal fascia. An anatomic and computed tomography study. AB - To study the medial extent of the posterior renal fascia and the perirenal space, the authors dissected two cadavers and reviewed 50 computed tomographic (CT) abdominal scans. The results demonstrated that the medial extent of the posterior renal fascia depends on the level in a vertical direction and its relationship to the kidney which varies at different levels. At the renal hilus, the fascia inserts posteromedially to the fascia of the quadratus lumborum along its lateral margin; more cranially, the line of insertion is more lateral, onto the diaphragmatic fascia; more caudally, the line of insertion is more medial, inserting onto the anterior surface of the quadratus lumborum. Therefore the posteromedial insertion of the posterior renal fascia extends medially, from the more laterally placed diaphragmatic fascia, to the lateral margin of the quadratus lumborum and then to the anterior surface of the quadratus lumborum, depending on the anatomic level. The clinical implication of these findings are discussed. PMID- 2322879 TI - Tuberculous empyema necessitatis. Computed tomography findings. AB - Two patients who presented with an anterior chest wall mass were evaluated by computed tomography (CT) scan and were found to have an associated thick-walled pleural collection, consistent with empyema necessitatis. In view of the increasing incidence of pulmonary and extrapulmonary Mycobacterium tuberculosis infection, the entity of tuberculous empyema necessitatis should be strongly considered when the described CT findings are present. PMID- 2322880 TI - CT demonstration of peritoneal metastases after intraperitoneal injection of contrast media. AB - Thirty-three patients with ovarian carcinoma who had no evidence of metastases or ascites demonstrated on computed tomography (CT) with and without contrast agent were examined with CT after injection of approximately 3000 cc of a 2.4% solution of nonionic contrast media into the peritoneum. After intraperitoneal injection with CT (IPC CT), 22 were diagnosed as having intraperitoneal metastases. Of these, 19 were found to be true positives and 3 false negatives. Three other patients diagnosed as normal were found to have metastases. In all patients the peritoneum was well outlined and generally any metastases smaller than 1 cm were demonstrated. It was possible to identify compartmentalization of the peritoneum and to determine the location of the lesion to be in the peritoneum or the extraperitoneal space. This information is necessary in the planning of chemotherapy, particularly endoperitoneal chemotherapy. Tiny metastases to the omentum or adherent loops of small bowel could not be seen well. PMID- 2322881 TI - Primary peritoneal neuroblastoma: computed tomography findings. AB - Primary peritoneal tumors are rare neoplasms. The computed tomography findings in an adult patient with a primary peritoneal neuroblastoma are described. Discussion of these uncommon neoplasms and this unusual presentation of neuroblastoma forms the basis of this report. PMID- 2322882 TI - Magnetic resonance imaging of hepatic adenoma. AB - A case of hepatic adenoma imaged by magnetic resonance imaging (MRI) as well as with angiography, computed tomography, and radionuclide imaging is presented. Pathological correlation is also presented. Review of the literature of MRI of hepatic adenoma and related tumors is discussed. PMID- 2322883 TI - Radiological diagnosis of thymoma in myasthenia gravis (MG). Review of a series of 523 surgically controlled patients. PMID- 2322884 TI - Magnetic resonance imaging of adult ovarian granulosa cell tumor. Case report. AB - We report the magnetic resonance imaging (MRI) findings in a unilocular multicystic adult granulosa cell tumor of the ovary. MRI, in conjunction with the clinical and laboratory findings, helped establish a preoperative diagnosis. PMID- 2322885 TI - Intraspinal air: an unusual manifestation of blunt chest trauma. AB - A case of intraspinal air following traumatic bronchial laceration is demonstrated by computed tomography. PMID- 2322888 TI - Radiology pathology conference. An 18-year-old man with a 4-month history of progressive neck and right shoulder pain. PMID- 2322887 TI - MRI findings of sciatic endometriosis. AB - Endometriosis is a rare cause of sciatic mononeuropathy. We report a woman with cyclic, menstruation-related hip pain associated with right leg weakness and sensory loss. Examination and electrodiagnostic studies suggested sciatic nerve dysfunction. Magnetic resonance imaging (MRI) revealed abnormal signal consistent with endometriotic tissue in the region of the right sciatic nerve. The abnormal signal partially regressed after treatment of the endometriosis. This case further illustrates the utility of MRI in the assessment of rare pelvic disorders. PMID- 2322889 TI - Extraperitoneal space. PMID- 2322886 TI - Mucocele of the appendix accurately diagnosed using computer tomography. AB - Mucocele of the appendix is rare so an accurate preoperative diagnosis is very difficult. We report, using computer tomography (CT) in combination with other diagnostic methods, one such correct preoperative diagnosis. PMID- 2322890 TI - Canadian Ophthalmological Society, 53rd annual meeting. 24-27 June 1990, Quebec, Canada. Abstracts. PMID- 2322891 TI - The effect of repeated intermittent hypoxia on pulmonary vasoconstriction in the newborn. AB - The effect of repeated intermittent hypoxia upon the basal pulmonary vascular tone in the newborn period is unknown. We therefore studied the central hemodynamic response to seven repeated intermittent hypoxic challenges in acutely prepared piglets under 2 weeks of age. Catheters were placed in the aorta, pulmonary artery, and atria, and an electromagnetic flow probe was positioned around the main pulmonary artery. Each hypoxic challenge (Fio2 = 0.14) lasted 5 min, and was separated by an equal duration of ventilation with air. Nine control animals were ventilated with air for 90 min, a period of time equivalent to the seven challenges in the experimental group, and subjected to one hypoxic challenge at the end. Hypoxia uniformly induced pulmonary vasoconstriction. Repeated intermittent hypoxic challenges produced a progressive increase in pulmonary artery pressure and vascular resistance, both during air ventilation and hypoxia. For each challenge, the vascular resistance value achieved during hypoxia was directly related to the immediately preceding air ventilation one, and the magnitude of hypoxic pulmonary vasoconstriction, defined as the incremental change in resistance from air to hypoxia, was not different from the first to the last challenge in the experimental group. In the control group the pulmonary vascular tone did not change during the 90 min of air ventilation, and the single hypoxic challenge induced an increase in pulmonary vascular pressure and resistance similar in magnitude to the first challenge in the experimental group. Indomethacin administration to five experimental animals, after the last challenge, reversed the increase in air ventilation pulmonary artery pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322892 TI - Corelease of neuropeptide Y like immunoreactivity with catecholamines from the adrenal gland during splanchnic nerve stimulation in anesthetized dogs. AB - The release of neuropeptide Y like immunoreactivity (NPY-li) from the adrenal gland was studied in relation to the secretion of catecholamines (CA: NE, norepinephrine; E, epinephrine) during the left splanchnic nerve stimulation in thiopental-chloralose anesthetized dogs (n = 16). Plasma concentrations of NE, E, and NPY-li were determined in the left adrenal venous and aortic blood. Adrenal outputs of NPY-li, NE, and E were 2.4 +/- 0.4, 1.4 +/- 0.2, and 7.3 +/- 1.7 ng/min, under basal conditions, respectively. These values increased significantly (p less than 0.05; n = 8) in response to a continuous stepwise stimulation at frequencies of 1, 3, and 10 Hz given at 3-min intervals during 9 min, reaching a maximum output of 4.6 +/- 0.9 (NPY-li), 240.2 +/- 50.2 (NE), and 1412.5 +/- 309.7 ng/min (E) at a frequency of 10 Hz. Burst electrical stimulation at 40 Hz for 1 s at 10-s intervals for a period of 10 min produced similar increases (p less than 0.05) in the release of NPY-li (4.8 +/- 1.0 ng/min, n = 8), NE (283.5 +/- 144.3 ng/min, n = 8), and E (1133.5 +/- 430.6 ng/min, n = 8). Adrenal NPY-li output was significantly correlated with adrenal NE output (r = 0.606; n = 24; p less than 0.05) and adrenal E output (r = 0.640; n = 24; p less than 0.05) in dogs receiving the burst stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322893 TI - 3,5-Diethoxycarbonyl-2,6-dimethyl-4-ethyl-1,4-dihydropyridine inactivates rat liver cytochrome P-450c, but not its orthologue, rabbit lung form 6. AB - Various rat liver cytochrome P-450 (P-450) isozymes are targets for mechanism based inactivation by 3,5-diethoxycarbonyl-2,6-dimethyl-4-ethyl-1,4- dihydropyridine (4-ethyl DDC). Unlike rat liver, which contains multiple P-450 isozymes, rabbit lung contains only three major isozymes referred to as forms 2, 5, and 6. We have examined the ability of 4-ethyl DDC to destroy P-450 heme in hepatic and pulmonary microsomes from untreated and beta-naphthoflavone (beta NF) treated rabbits. This compound destroyed 31% of the P-450 in either hepatic microsomal preparation, but was ineffective at lowering P-450 and heme levels in pulmonary microsomes when examined at a range of concentrations (0.45-5.0 mM). These data suggest that rabbit pulmonary P-450 forms 2, 5, and 6 are not targets for destruction by 4-ethyl DDC, despite the ability of this compound to inactivate rat liver P-450c, the orthologue of rabbit lung form 6. PMID- 2322894 TI - Responses of equine trachealis and lung parenchyma to methacholine, histamine, serotonin, prostanoids, and leukotrienes in vitro. AB - The responses of equine trachealis and lung parenchymal strips to a range of contractile agonists were studied. Equine trachealis responded to methacholine greater than histamine greater than serotonin as shown by the maximal responses but failed to respond to either leukotrienes (LT), prostaglandin F2 alpha, or U 44069. Equine parenchymal strips showed considerable tonal activity and responded to LTD4 congruent to LTC4 greater than U-44069 = LTE4 greater than methacholine congruent to histamine congruent to serotonin greater than prostaglandin F2 alpha as determined through pD2 values. Neither the concentration response curve to LTD4 nor the intrinsic tonal activity of the preparations was modified by pretreatment with either atropine or indomethacin, although the maximal response to LTD4 was reversed by addition of the LTD4 receptor antagonist, MK-571. Thus arachidonic acid metabolites, including LTs, must be considered potential mediators of equine small airway disease, a potential model of human bronchial asthma. PMID- 2322895 TI - Reflex control of vascular capacitance during hypoxia, hypercapnia, or hypoxic hypercapnia. AB - We tested the hypothesis that the changes in venous tone induced by changes in arterial blood oxygen or carbon dioxide require intact cardiovascular reflexes. Mongrel dogs were anesthetized with sodium pentobarbital and paralyzed with veruronium bromide. Cardiac output and central blood volume were measured by indocyanine green dilution. Mean circulatory filling pressure, an index of venous tone at constant blood volume, was estimated from the central venous pressure during transient electrical fibrillation of the heart. With intact reflexes, hypoxia (arterial PaO2 = 38 mmHg), hypercapnia (PaCO2 = 72 mmHg), or hypoxic hypercapnia (PaO2 = 41; PaCO2 = 69 mmHg) (1 mmHg = 133.32 Pa) significantly increased the mean circulatory filling pressure and cardiac output. Hypoxia, but not normoxic hypercapnia, increased the mean systemic arterial pressure and maintained the control level of total peripheral resistance. With reflexes blocked with hexamethonium and atropine, systemic arterial pressure supported with a constant infusion of norepinephrine, and the mean circulatory filling pressure restored toward control with 5 mL/kg blood, each experimental gas mixture caused a decrease in total peripheral resistance and arterial pressure, while the mean circulatory filling pressure and cardiac output were unchanged or increased slightly. We conclude that hypoxia, hypercapnia, and hypoxic hypercapnia have little direct influence on vascular capacitance, but with reflexes intact, there is a significant reflex increase in mean circulatory filling pressure. PMID- 2322896 TI - Naloxone's effect on the inotropic and chronotropic responses of isolated, electrically stimulated or spontaneously beating rat atria. AB - Experiments were conducted to determine (i) how naloxone administration alone could modify the inotropic (in electrically stimulated (ES) rat atria) and both the inotropic and chronotropic responses (in spontaneously beating (SB) rat atria) isolated from normotensive and hypotensive (hemorrhaged) rats, and (ii) how naloxone administration would modify the inotropic and chronotropic responses of isolated rat atria previously administered an opiate agonist (morphine), a muscarinic agonist (carbachol), or an alpha- and beta-adrenergic agonist (noradrenaline). Naloxone (51-340 microM) added to ES atria caused a delayed but dose-related decrease in atrial tension (AT), whereas in SB atria, naloxone caused atrial heart rate (AHR) to fall and atrial tension (AT) to increase. Naloxone (68-340 microM), given to SB atria from acutely hypotensive rats, caused a similar increase in atrial tension as seen in the "normotensive" isolated (SB) atria and a similar decrease in atrial heart rate. Morphine sulphate (MS), 37-375 microM, administered to ES atria caused a delayed fall in AT; which was further decreased when naloxone (340 microM) was also added. In the SB atria, morphine caused a dose-related decrease in atrial heart rate whereas atrial tension increased. In SB preparations, atrial heart rate fell even further when naloxone was added to morphine compared with when morphine sulphate was given alone, whereas atrial tension was increased. Noradrenaline (3 or 12 microM) caused a positive, dose-related inotropic response in the ES atria, effects not influenced by the addition of naloxone. In the SB atria, naloxone caused no change in the dose-related increases in atrial tension and heart rate when combined with the lower dose of noradrenaline but decreased AT when combined with 12 microM noradrenaline, compared with when this dose of noradrenaline was given alone. Carbachol (683 nM-1.37 microM) caused a dose-related decrease in atrial tension in ES atria, which was reversed completely by the addition of naloxone. In SB atria, carbachol decreased both atrial tension and heart rate, and with the addition of naloxone (340 microM), a further slight drop in atrial heart rate occurred, but concurrently, a marked rise in atrial tension was observed. The results indicate that naloxone can act with receptors directly within atrial tissue to cause changes in atrial tension and heart rate. The comparable delayed responses of morphine and naloxone suggest their effects are mediated by nonopiate receptors which, in time, cause decreases in calcium influx into the atria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2322897 TI - Effects of increased perfusion pressure on medullary collecting duct function. AB - The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 +/- 4.1 to 51 +/- 9.3% (p less than 0.01) and from 65.7 +/- 6.0 to 42.7 +/- 9.1% (p less than 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment. PMID- 2322898 TI - Bifemelane induces translocation of protein kinase C in the CA3, but not the CA1, region of guinea-pig hippocampus. AB - We made use of the [3H]phorbol 12,13-dibutyrate binding assay to investigate the effects of bifemelane on the subcellular distribution of protein kinase C in the CA3 and CA1 regions of guinea-pig hippocampal slices. Bifemelane, a drug that augments the long-term potentiation in the CA3 region, significantly induced the translocation of [3H]phorbol 12,13-dibutyrate binding activity from the cytosol to the membrane in a dose-dependent manner (10(-8) to 10(-6) M) and with no effects on total binding activity in the CA3 region. Bifemelane, at a concentration of 10(-6) M, was without effect on the subcellular distribution of [3H]phorbol 12,13-dibutyrate binding activity in the CA1 region. These observations suggest that bifemelane acts directly on the hippocampus to induce translocation of protein kinase C in the CA3 region. Such an effect may be associated with the bifemelane-induced augmentation of the long-term potentiation in this region of the brain. PMID- 2322899 TI - Pulmonary vascular resistance in adult rats exposed to hypoxia in the neonatal period. AB - Newborn rats were exposed to hypoxia (10% O2 + N2) from 24 h to day 6 of neonatal life and then returned to room air until 45 days of age (experimental). The rats were anaesthetized, heparinized, and exsanguinated. The chest was opened and the lungs were perfused with diluted autologous blood at a constant flow rate (Q). The pulmonary arterial pressure (Pa) and venous pressure (Pv) were monitored. The properties of the pulmonary vasculature were assessed by measuring baseline vascular resistance, PVR = (Pa-Pv)/Q, segmental pressure gradients (double occlusion technique), pressure-flow relationship, hypoxic pressor response (HPR, 3% O2), and the response to 0.5 microgram bolus of angiotensin II (AII). These were compared with similar measurements on age-matched control animals never exposed to hypoxia. The perfusate hematocrit and gases were not significantly different between the two groups. The PVR normalized to body weight was 30% higher in the experimental groups (p less than 0.005). The double occlusion results (obtained at a flow rate of 13 mL/min) revealed that this increase in resistance was primarily due to the increase in the postcapillary resistance. HPR was primarily in the upstream segment in both groups but was larger in the experimental group. In contrast, the response to AII occurred in both the upstream as well as in the downstream vascular segments and did not differ between the two groups. We conclude that adult rats exposed to hypoxia in the neonatal period have elevated pulmonary vascular resistance and increased vascular reactivity to hypoxia. PMID- 2322900 TI - Inhibitory innervation of colonic smooth muscle cells and interstitial cells of Cajal. AB - The effect of neural inhibition on the electrical activities of circular and longitudinal colonic smooth muscle was investigated. In addition, a comparative study was carried out between circular muscle preparations with and without the "submucosal" and "myenteric plexus" network of interstitial cells of Cajal (ICC) to study innervation of the "submucosal" ICC and to investigate whether or not the ICC network is an essential intermediary system for inhibitory innervation of smooth muscle cells. Electrical stimulation of intrinsic nerves in the presence of atropine caused inhibitory junction potentials (ijps) throughout the circular and longitudinal muscle layers. The ijp amplitude depended on the membrane potential and not on the location of the muscle cells with respect to the ICC network. Neurally mediated inhibition of the colon resulted in a reduction in amplitude and duration of slow wave type action potentials in circular and abolishment of spike-like action potentials in longitudinal smooth muscle, both resulting in a reduction of contractile activity. With respect to mediation by ICC, the study shows (i) "submucosal" ICC receive direct inhibitory innervation and (ii) circular smooth muscle cells can be directly innervated by inhibitory nerves without ICC as necessary intermediaries. The reversal potential of the ijp in colonic smooth muscle was observed to be approximately -76 mV, close to the estimated potassium equilibrium potential, suggesting that the nerve-mediated hyperpolarization is caused by increased potassium conductance. PMID- 2322901 TI - Reflections from the trenches. PMID- 2322902 TI - "Health care security"? Not in Ontario. PMID- 2322903 TI - CMA's response to abortion bill. PMID- 2322904 TI - HIV testing. PMID- 2322905 TI - Nonvalidated food allergy tests. PMID- 2322906 TI - Hypercholesterolemia and atherogenesis. PMID- 2322907 TI - Nonprescription cough and cold remedies. PMID- 2322908 TI - Should trends be reported? PMID- 2322909 TI - Making hockey safer. PMID- 2322910 TI - Bedside testing of the blood glucose level in neonates: what to use? PMID- 2322911 TI - The future of medical research in Canada. PMID- 2322912 TI - Health and medical research funding in the United Kingdom. PMID- 2322913 TI - Use of methylphenidate for attention deficit hyperactivity disorder. Mental Health Committee, Canadian Paediatric Society. PMID- 2322914 TI - Determinants of plasma glucose level and diabetic status in a northern Canadian Indian population. AB - We conducted a cross-sectional survey of 704 Indians aged 20 to 64 years in six remote communities in northern Ontario and Manitoba to determine the factors associated with the fasting plasma glucose and glycosylated hemoglobin levels and diabetic status, defined by past history and current fasting plasma glucose level. Multivariate analyses for the 671 subjects with complete data showed that triglyceride level, age and body mass index (BMI) were significant predictors of the log fasting plasma glucose level and the log glycosylated hemoglobin level; for the latter, waist/hip ratio, history of diabetes mellitus among first-degree relatives and low level of education were additional predictors. Significant risk factors for diabetes as a dichotomous variable included triglyceride level, age, BMI and family history of diabetes. Although energy intake per unit of body weight was lower among subjects with diabetes than those without diabetes, possibly reflecting the lower physical activity level of diabetic subjects, the former consumed significantly more "calorie-adjusted" protein and less carbohydrate than the latter. The findings are consistent with studies in other populations. Further study is needed to determine the natural history of diabetes and its metabolic consequences and to assess the effect of dietary alteration and promotion of physical activity on the incidence of the disease. PMID- 2322915 TI - Chronic eosinophilic pneumonia associated with thrombocytosis and pleural effusion. PMID- 2322916 TI - Cholestatic jaundice associated with lovastatin (Mevacor) therapy. PMID- 2322917 TI - Elementary schools receive new AIDS teaching kit. PMID- 2322918 TI - Medical computing in the '90s: get ready for a Big Mac attack. PMID- 2322919 TI - You and your practice partner: get it down on paper. PMID- 2322921 TI - Templeton's travels: sniffing out the world's emerging markets. PMID- 2322920 TI - The Third World: AIDS finds a comfortable home. PMID- 2322922 TI - Medical ethics and women. PMID- 2322923 TI - Influence of host age and tumor load on the growth and catecholamine content of C 1300 murine neuroblastoma in situ. AB - The influence of host age and tumor load on survival time, tumor growth parameters and biochemical differentiation, as characterized by tumor catecholamine content, were investigated. A/J mice were implanted with tumor loads of 10(4), 10(5) and 10(6) disaggregated C-1300 murine neuroblastoma (MNB) cells at 1, 7, 14, 21 and 56 days of age. Studies performed in mice between 7 and 56 days of age demonstrated that MNB tumorigenicity, tumor growth rate, host survival and catecholamine content were independent of host age and tumor load whereas, tumor onset time was influenced by both factors. In contrast to older animals, tumor onset time and catecholamine content were decreased and tumor growth rate increased in 1-day-old mice. This difference may be due to the presence of endogenous growth factor(s) that modulate cell proliferation in the immediate post-natal period. PMID- 2322924 TI - Plasma membrane properties of cultured local LM cell tumors and metastases from athymic (nude) mice. AB - Some cell surface membrane properties of tumors may depend upon the host tissue site. Therefore, local tumors and lung metastases were excised from athymic (nude) mice injected subcutaneously with LM fibroblasts. The excised local tumors and lung metastases were cultured in chemically-defined, serum-free medium to characterize their plasma membrane properties without complicating factors such as site of growth, presence of host inflammatory cells, and variation in nutrition. Plasma membranes were isolated from the cultured local tumor cells and cultured metastatic cells. The specific activities of (N+,K+)-ATPase and 5' nucleotidase were elevated and decreased, respectively, in plasma membranes from metastatic cells as compared to local tumor cells, a finding consistent with data from directly excised local tumors and lung metastases. Plasma membranes of metastatic cells had a lower ratio of sterol/phospholipid, higher ratio of phosphatidylcholine/phosphatidylethanolamine, and no differences in phospholipid unsaturated/saturated fatty acid ratio compared to plasma membranes from the locally-derived tumor cells. Plasma membranes of metastatic cells were more fluid (lower limiting anisotropy) than those of local tumor cells as indicated by multifrequency phase and modulation fluorometry and the fluorescence probe molecule, 1,6-diphenyl-1,3,5-hexatriene. Thus, the higher fluidity of metastatic as compared to local tumor plasma membranes was not due to differences in site of growth, host cell contamination, and/or nutrition. PMID- 2322925 TI - Evidence of lipid peroxidation in premenopausal women with mammographic dysplasia. AB - We have compared the urinary excretion of the mutagen malonaldehyde in premenopausal women at different risks for breast cancer as determined by the appearance of the breast parenchyma on mammography. Thirty women with extensive mammographic densities were compared with 16 controls without these radiological changes. Malonaldehyde was measured in 24-h urine samples from both groups and excretion in 30 women with mammographic dysplasia (high risk) was found to be approximately double that of 16 women without these radiological changes (P less than 0.02). These results suggest that mammographic dysplasia may be associated with lipid peroxidation and raise the possibility that mutagenic products generated by this process may influence breast cancer risk. PMID- 2322926 TI - Induction of multifocal pancreatic cancer after inoculation of hamster pancreatic cancer cell line (PC-1) into a defined area of homologous pancreatic tissue. AB - Inoculation of the pancreatic cancer cell line PC-1 into a defined area of the tail of the hamster pancreas led to development of multiple cancerous foci in the body of the pancreas along the main pancreatic duct. Each carcinoma showed identical histological characteristics and was completely separated from the others by regions of normal pancreatic tissue. This observation suggests spread of the cancer from the primary site in discontinuity through the ductal system of the pancreas. PMID- 2322927 TI - Unscheduled DNA synthesis and HPRT mutation in fetal Syrian hamster and human respiratory epithelial cells exposed to ethylnitrosourea. AB - We previously reported that the chromosomes of fetal Syrian hamster respiratory epithelial cells were less stable toward ethylnitrosourea (ENU) than those of comparable human cells. Following this, we compared the sensitivity of genetic materials of the same cell systems to the same mutagen in terms of unscheduled DNA synthesis (UDS) and mutation at HPRT locus (HPRT-). UDS occurred 5 (with 0.1 mg ENU/ml) to 7 (with 0.4 mg ENU/ml) times more frequently in the hamster cells than in the human cells. This much lower UDS frequency in human cells cannot be solely explained by the fact that the human cells possess only a moderately larger (1.6 to 2.9 times) size of intracellular deoxythymidine triphosphate (dTTP) pool than the hamster cells. This finding would thus indicate that the hamster cells actually carry out DNA repair, whether correct or aberrant, more often than the human cells. Moreover, HPRT- was also 5 (at 0.4 mg/ml) to 26 (at 0.8 mg/ml) times more frequent in the hamster cells than in the human cells. Therefore, the current results suggest that the DNA repair mechanisms of the hamster cells are less accurate and more unstable than those of the human cells. Our previous findings with regard to the chromosomal stability give support to this hypothesis. PMID- 2322928 TI - Oxidation of 2-amino-9-beta-D-ribofuranosylpurine-6-sulfenamide to the corresponding 6-sulfonamide facilitates changes in biologic characterization that include activity against thiopurine-refractory experimental leukemia. AB - Preclinical investigations in vivo revealed unexpected differences in the biological characteristics of 2-amino-9-beta-D-ribofuranosylpurine-6-sulfenamide (sulfenosine, 1) and 2-amino-9-beta-D-ribofuranosylpurine-6-sulfonamide (sulfonosine, 2), two novel but structurally related derivatives of 6 thioguanosine (6TGR). Strikingly, the addition of a fully oxidized sulfur atom at the 6 position of sulfenosine produced a purine derivative (sulfonosine) that was remarkably active against experimental leukemia resistant to treatment with either sulfenosine or 6TGR. This slight structural modification also appeared to influence solubility, scheduling capability, and oral activity as well as penetration of the central nervous system (CNS) and the onset of cellular resistance. These findings underscore the dramatic changes in biologic activity that can be produced by subtle modifications in molecular structure. We trust they may also contribute to the development of improved clinical therapy. PMID- 2322929 TI - Antitumor potential of low-dose chemotherapy manifested in combination with immunotherapy of Viva-Natural, a dietary seaweed extract, on Lewis lung carcinoma. AB - Beneficial antitumor effects of low-dose chemotherapy (Adriamycin, BCNU, cisplatin, 5-fluorouracil, methotrexate, 6-thioguanine or vincristine) combined with an immunotherapy with a partially purified polysaccharide of Viva-Natural, an edible seaweed extract, have been demonstrated against intraperitoneally implanted Lewis lung carcinoma in syngeneic mice. Adriamycin, cisplatin, 5 fluorouracil and vincristine at low doses, that were not effective when given alone, manifested antitumor activity when combined with the polysaccharide fraction of Viva-Natural. Other three drugs (BCNU, methotrexate and 6 thioguanine) at the noneffective low doses exhibited no further antitumor activity when combined with Viva-Natural. Cytotoxic activation of peritoneal macrophages in mice has been induced by single administration of the polysaccharide fraction of Viva-Natural, but the combined regimen of low dose drugs plus viva-Natural was no more effective than Viva-Natural alone. Therefore, the mechanism of action of the beneficial combination is not clear yet. PMID- 2322930 TI - Detoxifying potential of thioproline against N-nitroso compounds, N nitrosodimethylamine and N-nitrosocimetidine. AB - Thioproline (TPRO), an effective nitrite trapping agent in vivo, was examined for its detoxifying ability in rats against N-nitrosodimethylamine (NDMA) and N nitrosocimetidine (NCIM). When NDMA (37-101.5 mg/kg) was administered with TPRO (532 mg/kg), no influence of TPRO on NDMA-induced lethality and histological results in liver were observed. NDMA oxygenase activity measured by formaldehyde formation was not affected either. Denitrosation is a route of detoxication of N nitroso compounds. When NCIM (100 mg/kg), a direct acting mutagen but not carcinogen, was given by gavage with TPRO, urinary excretion of N nitrosothioproline (NTPRO) in rats apparently increased compared with TPRO alone. This result shows that TPRO is a trapping agent in vivo for nitrosating (NO) species originating from N-nitroso compounds, e.g., NCIM, which are denitrosated non-enzymatically in stomach acidic conditions. Transnitrosation from NDMA to TPRO, where enzymatic denitrosation is required, did not occur in measurable amount after oral administration of NDMA and TPRO. PMID- 2322931 TI - Xanthine oxidase levels in human brain tumors. AB - Xanthine oxidase is most recognized for its role as the rate-limiting enzyme in nucleic acid degradation through which all purines are channelled for terminal oxidation. The enzyme serves as a source of oxygen-derived free radicals which induce both cellular injury and edema as well as changes in vascular permeability. In the study we compared xanthine oxidase levels of human brain tumors with normal brain tissues. Statistical evaluation of our results shows significantly higher xanthine oxidase levels in tumoral brain tissues. However, xanthine oxidase has not any significance for the differentiation of tumor types among each others. The oncotypes studied were meningioma and astrocytoma. PMID- 2322932 TI - Analysis of factors influencing clonogenic growth in vitro of cells from ovarian carcinoma patients. AB - Clonogenic growth (defined as the formation of greater than or equal to 5 colonies per 5 x 10(5) viable nucleated cells per plate) of ovarian cancer specimens assessed in our clonogenic assay system was significantly associated with the proportion of tumor cells in the suspensions plated (N = 87; P = 0.0006), although there was no quantitative relationship with the corresponding plating efficiencies. An inverse correlation was observed between monocytes/macrophages/mesothelial cells (M) proportion and clonogenic growth (P = 0.013). These associations were most evident when only effusions were considered. Univariate analyses identified tumor cell content, M proportion and, to a lesser degree, granulocyte content as the only factors out of 12 examined to be correlated with colony formation. Multivariate analysis using a logistic regression model identified the proportion of tumor cells as the only significant factor predicting clonogenic growth in vitro (P = 0.0006). The overall accuracy of prediction for growth or non-growth was 63.2%. PMID- 2322933 TI - Vasoactive intestinal polypeptide (VIP) induces calcium mobilization in the human neuroblastoma cell line SK-N-SH. AB - Release of catecholamines, a Ca2(+)-dependent process, is the most useful biochemical marker in the diagnosis of neuroblastoma. Unfortunately, its stimulus is still unknown. We found that vasoactive intestinal polypeptide (VIP), in addition to acetylcholine and muscarine (but not nicotine), causes elevation of the cytoplasmic Ca2(+)-concentration in the highly differentiated human neuroblastoma cell line SK-N-SH, with or without the presence of extracellular Ca2+. Additionally, VIP was detected in SK-N-SH cells (0.65 ng/10(6) cells). Based on these observations and the fact that neuroblastoma is not innervated in vivo, we hypothesize that in this tumor VIP is responsible for Ca2(+)-dependent release of catecholamines in an autocrine or paracrine fashion. PMID- 2322934 TI - Liver tumor promoting ability of corn oil gavage in B6C3F1 male mice. AB - In chronic carcinogenic bioassays, chemicals being tested with low water solubility have been administered via corn oil gavage. The present study examined the effect of chronic corn oil gavage on hepatic tumor formation in the B6C3F1 male mouse. Mice were initiated with diethylnitrosamine (DENA) either at 15 days of age with a single i.p. injection (5 micrograms/gbw) (protocol 1) or at 4 weeks of age via the drinking water (15 mg/l) for a duration of 3 weeks (protocol 2). At weaning (protocol 1) or 8 weeks of age (protocol 2) initiated and untreated mice were administered either corn oil at a dose of 0.15 ml via gavage (once a day, 5 days/wk) or saline (0.15 ml via gavage, once a day 5 days/wk). All mice were killed at 28 weeks of age and hepatic lesions were quantitated. Only mice exposed to DENA demonstrated hepatic tumors. Mice treated with DENA (at 15 days of age) and corn oil gavage exhibited a significant decrease in the number of hepatic adenomas compared with DENA (at 15 days of age) only treated mice. No difference was noted in the number of hepatic adenomas between mice treated with DENA (at 4 wks of age) and corn oil gavage and mice exposed to DENA (at 4 wks of age) only. PMID- 2322935 TI - Injury induced by fatty acids or bile acid in isolated human colonocytes prevented by calcium. AB - Measurement of the modulation of the growth fraction of isolated normal colonocytes from adult subjects in primary monolayer culture was used as a sensitive quantitative assay to evaluate toxic effects of several endogenous compounds found within the colon. This assay was used to study the role of CaCl2 in blocking cell injury. When added simultaneously with the injurious agent, 5-10 mM CaCl2 blocked the toxicity of physiological concentrations of deoxycholic acid, oleic acid, palmitic acid and linoleic acid. PMID- 2322936 TI - Age-related decrease of pulmonary metastasis of rat mammary carcinoma by activated natural resistance. AB - We found that the number of pulmonary metastatic foci of spontaneously developed rat mammary carcinoma (SST-2), when transplanted subcutaneously in spontaneously hypertensive (SH) rats, decreased with aging. In the SST-2-bearing SH rats, it was observed that T cell functions progressively declined while activities of macrophages and natural killer cells were non-specifically activated by increasing age. To examine the mechanisms of the age-related decrease of pulmonary metastasis in SH rats, we treated the SST-2-bearing rats with anti (asialo-GM1) antibody and/or carrageenan, which are known to suppress the functions of macrophages and natural killer cells, or with poly(I).poly(C), which is a stimulator to natural killer cells. The anti-(asialo-GM1) treatment significantly increased the number of pulmonary metastatic foci in both young and old SH rats, while poly(I).poly(C) significantly decreased the lung nodules in the old SH rats. These result suggest that the decrease of pulmonary metastasis in the SH rats with aging may be closely correlated with non-specifically activated natural killer cells and macrophages, though it should be also considered that non-immunological tumor-host interactions may be involved in the differences between the young and the old SH rats. PMID- 2322937 TI - Mycoplasma capricolum membranes induce tumor necrosis factor alpha by a mechanism different from that of lipopolysaccharide. AB - Heat-inactivated (60 degrees C, 45 min) Mycoplasma capricolum strain JR cells activate murine macrophages to secrete high levels of tumor necrosis factor alpha (TNF alpha) and to lyse tumor target cells efficiently. Fractionation of the intact M. capricolum cells, obtained from cells harvested at the exponential phase of growth, shows that their capacity to induce TNF alpha secretion by macrophage resides exclusively in the membrane fraction. The macrophage-mediated cytolysis following activation by M. capricolum membranes was significantly inhibited by specific anti-recombinant murine TNF alpha antibodies. M. capricolum membranes are a potent inducer of TNF alpha as the commonly used bacterial lipopolysaccharide, indicated by their dose-response curve for macrophage activation. Our study further showed that M. capricolum membranes and lipopolysaccharide synergize to augment TNF alpha secretion by C57BL/6-derived macrophages markedly. Moreover, lipopolysaccharide-unresponsive C3H/HeJ-derived macrophages, were pronouncedly activated by M. capricolum membranes, which do not contain lipopolysaccharide. These findings suggest that the mechanism by which M. capricolum membranes activate macrophages differs from that of lipopolysaccharide. Results of preliminary experiments show that human monocytes as well secrete TNF alpha following activation by M. capricolum membranes. Thus, in contrast with the prohibitive toxicity of lipopolysaccharide to animals and humans, M. capricolum membranes, which contain no lipopolysaccharide and are nontoxic in nature, may be of therapeutic value in the treatment of cancer. PMID- 2322939 TI - [An epidemiological study on coronary sudden death in Beijing]. AB - An epidemiological study on coronary sudden death (CSD) had been carried out in defined areas of Beijing, covering a population of approximately 700,000, for a period of two years, 1984 to 1985. A total of 201 cases of CSD had been registered. The data showed: 1) half of the coronary death in the population were CSD and the rate of CSD increased with age; 2) the rate of CSD in males was higher than that in females; 3) most cases of CSD had a history of cardiovascular diseases; 4) 85% of CSD cases died within 6 hours after acute onset; 5) about half of the CSD cases had predominant symptoms with lower specificity. Some issues about the diagnostic criteria of CSD and cardiac-pulmonary resuscitation outside hospital in the communities of Beijing were discussed in detail. PMID- 2322938 TI - Parallel antitumor, granuloma-forming and tumor-necrosis-factor-priming activities of mycoloyl glycolipids from Nocardia rubra that differ in carbohydrate moiety: structure-activity relationships. AB - Multiple intravenous injections (30 micrograms, ten times) in ICR mice of trehalose dimycolate and glucose monomycolate from Nocardia rubra, containing C36 48 mycolic acids, showed a prominent antitumor effect on a subcutaneously implanted sarcoma-180, an allogeneic sarcoma of mice with a significant granuloma formation in lungs, spleen and liver. On the other hand, mycoloyl glycolipids other than glucose monomycolate and trehalose dimycolate, such as mannose or fructose mycolate, showed no significant activity for tumor regression or granuloma formation in mice. Trehalose dimycolate and glucose monomycolate from N. rubra, and glucose monomycolate with C56-60 mycolic acids from Rhodococcus terrae also showed a distinctive priming activity for tumor necrosis factor (TNF), when lipopolysaccharide from Escherichia coli was administered as an eliciting agent. The TNF activity in the sera of mice was abrogated almost completely by anti-(murine TNF alpha) antibody with protein-A-agarose. Again in contrast, mannose and fructose mycolate from N. rubra and glucose monomycolate with C30-34 mycolic acids from Rhodococcus equi did not show such activities in mice. Meth-A, a syngeneic fibrosarcoma of BALB/c mice, was less sensitive to administration of glycolipids than sarcoma-180. These results indicated that the existence of a glucose or trehalose molecule was necessary for the expression of immunomodifying activities among various mycoloyl glycolipids differing in carbohydrate structure. However, since the administration of lipopolysaccharide was essentially required as an eliciting agent for the induction of TNF, while no eliciting agent was required for the antitumor activities, TNF does not seem to contribute directly to the antitumor activities of mycoloyl glycolipids in our systems. There was, however, a parallel structure-activity relationship among granuloma-forming, antitumor and TNF-priming activities, indicating that the structures of both the carbohydrate moiety and the mycoloyl residues influenced an initial step, such as macrophage activation, commonly and profoundly. PMID- 2322940 TI - [Preliminary study on leprosy subclinical infection and its sero-epidemiology]. AB - The detection of subclinical infection with M. leprae among 360 household contacts of leprosy and 95 healthy controls was conducted with PGI-ELISA in leprosy-endemic areas. The relationship of age at infection, and onset with epidemic trends was explored basing on the distribution features of subclinical infection with M. leprae in household contacts of leprosy. In addition, the multiple linear regression was used to analyse the factors affected the level of antibody in leprosy. PMID- 2322941 TI - [An analysis of survivals of lung cancer in Beijing during 1977-1982]. AB - An Survival analysis include sex, age, diagnosis bases, treatment and survival status. Of lung cancer cases during 1977-1982 in 4 districts covering a population of 2.3 million in Beijing was studied by using Kaplan-Meier and Cox regression methods. Survival curves of 3005 lung cancer cases came down alongside the time last; and came down alongside the growth of age except the age group younger than 40 years. In addition, sieved result of complex factors, the authors got a model of six covariable. The survival time was obviously effected by age, type of pathology, complication in lung, state of metastasis, operation treatment and radiotherapy. PMID- 2322942 TI - [The relationship between Mo, Cu in drinking water and endemic fluorosis]. AB - Based on the investigation and analysis of 97 samples of drinking water from an endemic fluorosis area, and 32 samples from a non-endemic fluorosis area, the author suggested that the Mo, Cu content and the changes of their proportions should be considered an important factor in addition to the content of fluorine. In the area where the fluorine is above 2ppm, the higher the proportion of Mo, Cu and F in drinking water, the less serious the disease is. At the same time, it is found that a change in the proportion of Mo and Cu also influences this disease. The higher the proportion of Mo and Cu, the more diseases will occur. PMID- 2322943 TI - [Quality of retrospective survey of deaths and its evaluation]. AB - An imitative retrospective survey (RS) of deaths was carried out to evaluate the errors and quality of the retrospective survey by using the data on Qidong Death Cause Registry. Results showed that the agreement rates for death-cause, death age and death-date of RS were 79.69%, 67.97% and 58.98%, respectively. The total agreement rate for the three items was 31.95%, in which 52.71% in liver cancer, 25.00%, other cancers, 21.05%, other diseases, and 26.32%, accidents. Because some of the errors were cancelled out each other, the mis-report rates for the above diseases were 4.65%, 15.63%, 14.47%, and 10.53%, respectively, and the statistical breakdown of data, age-group and death-time distributions met basically with the data on registration (P greater than 0.05). This study indicates that the errors of the data from RS are rather higher compared with data on registration, yet the data on the whole can reflect the population distribution, time trends and epidemic intensity of diseases investigated, RS might be considered as a mean of getting historical data, but its application and evaluation should be cautious. PMID- 2322944 TI - [Matched investigation of risk factors in coronary heart patients with gallstones]. AB - Seventy-five cases of coronary heart disease with gallstones and another 75 cases without gallstones as controls were studied. The positive rates of previous cholecystitis and chronic intestinal diseases, and familial history of gallstone in the first group were obviously higher than those in the control group (P less than 0.05 & 0.11). The odd ratio (OR) was 4.22, 9.00 and 6.00, respectively. There was no difference in high serous lipid level, obesity, high cholesterol and fat intake (P greater than 0.05) neither group took clofirrate. It demonstrated that susceptible factors for coronary heart disease patients to develop gallstones are probably the same as in general population. The imbalance of lipoid metabolism had no direct associate with gallstones. The synergistic action of the imbalance of lipid metabolism and administration of some kinds of medicine might be a susceptible factor for coronary heart disease patients to develop gallstones. PMID- 2322945 TI - [A report on systolic hypertension in 1682 elderly peasants in Chengdu area]. AB - Blood pressures of 1682 elderly peasants in Chengdu were measured at cluster random. The prevalence rate of hypertension was 15.7% and higher than that in early elderly (P less than 0.01). The rate of systolic hypertension was 75.4% and increased with the increase of age. The rate in females was higher than that in males (P less than 0.01). Electrocardiograms of these hypertension persons were analyzed with Minnesota code, and the incidence rates of two types were not statistically significant. These results show that the change of heart function resulted from hypertension is related with the rise of systolic pressure as well the rise of diastolic pressure. PMID- 2322946 TI - Structural plugs at microtubule ends may regulate polymer dynamics in vitro. AB - Microtubules contain in their lumens distinct structures (plugs) that influence their dynamic behavior in vitro. As observed by electron microscopy, plugs are stain-occluding structures 10-30 nm in length that occur along the lengths and at the ends of microtubules. Plugs occur at a frequency of 20-40% at the ends of microtubules assembled from cycled microtubule protein containing MAPs. While the composition of plugs is not known, preliminary evidence suggests that they are accretions of tubulin, that they are labile, and that they are more common in preparations containing MAPs. When polymers are induced to depolymerize by endwise subunit dissociation, the frequency of plugged microtubule ends increases transiently, suggesting that plugs temporarily stabilize microtubules. The functional significance of plugs may be that they prevent the sudden complete loss of microtubules through catastrophic disassembly. It is possible that plugs, by slowing the rate of disassembly, enable a polymer to add GTP-tubulin subunits, thereby forming a stabilizing GTP-cap. These observations suggest that plugs may stabilize polymers and account for the frequent transitions from shortening to growing phases that characterize dynamic instability. PMID- 2322947 TI - Screening pregnant women for Chlamydia--Quebec. PMID- 2322948 TI - Herpes gladiatorum at a high school wrestling camp-United States. PMID- 2322949 TI - Fluorescence postlabeling assay of cis-thymidine glycol monophosphate in X irradiated calf-thymus DNA. AB - DNA damage was induced by irradiating calf-thymus DNA with a GE Maxitron-250 as an X-ray source. The use of nitrous oxide as a scavenger of solvated electrons in the irradiation process, resulted in essentially a monoreactant system of the biologically important hydroxyl radical. A novel approach combining the enzymatic digestion of the irradiated DNA to nucleoside 5' monophosphates and fluorescence postlabeling was applied to detect a specific modified nucleotide induced by ionizing radiation, namely the 5,6-dihydroxy-5,6-dihydrothymine lesion. This modification, often referred to as the glycol lesion, is polar and is generated mainly as the cis stereoisomers. In order to demonstrate the detection of this lesion in DNA by fluorescence labeling, the lesion was first produced chemically in a DNA model compound d(CGTA). The modified oligomers were isolated intact by HPLC and characterized by NMR as cis stereoisomers of glycol derivatives of d(CGTA). The major isomer of the modified d(CGTA) was enzymatically digested to yield 5' monophosphates. The digest was chromatographed by HPLC to enrich the modified nucleotide. The fraction containing the modified nucleotide was labeled with dansyl chloride. The fluorescent labeled nucleotide was chromatographed by HPLC. The same overall procedure was applied to DNA X-irradiated in aqueous solution. With a conventional fluorescence detector, HPLC analysis of the fluorescence labeled nucleotides detected 1 modified nucleotide/10(6) normal nucleotides from 100 micrograms DNA. The two cis glycol lesions were detected in the irradiated DNA by co-chromatography with fluorescent labeled markers. The initial assay of the modified oligomer demonstrated that the same stereoisomer of cis glycol was induced as a major modified nucleotide by both chemical oxidation and ionizing radiation. PMID- 2322950 TI - Metabolism of benzo[a]pyrene and (-)-trans-benzo[a]pyrene-7,8-dihydrodiol by freshly isolated hepatocytes of brown bullheads. AB - The metabolism of [3H]benzo[a]pyrene (BP) and (-)-trans-[14C]7,8-dihydroxy-7,8 dihydrobenzo[a]pyrene (BP-7,8-diol) was studied in freshly isolated hepatocytes of the wild benthic fish, brown bullhead (Ictalurus nebulosus). Bullhead hepatocytes incubated with 40 microM [3H]BP for 1 h metabolized BP to water soluble metabolites which were separated on silica gel t.l.c. plates to reveal conjugates with glucuronic acid, glutathione, and sulfate (51%, 14% and 4% of total metabolites, respectively). Additional metabolites that were extractable with ethyl acetate were separated by reversed phase HPLC to reveal only two major metabolites: BP-9,10-dihydrodiol and BP-7,8-diol (13% and 2.6% of total metabolites, respectively). Hepatocytes isolated from individual fish displayed an 11-fold variability in the rates at which they metabolized BP (756 +/- 167 pmol x mg dry wt-1 x h-1), which correlated negatively (r = -0.7, P less than 0.01) with an 18-fold variability in the glycogen content of the cells. Hepatocytes isolated from the same fish, in parallel incubations under the same optimum conditions, metabolized BP-7,8-diol 4.5-fold faster than they metabolized BP. The variability in the rate of BP-7,8-diol metabolism was about 7-fold. Major metabolites included glutathione conjugates, glucuronides and sulfates (35%, 25% and 30% of total metabolites, respectively). These conjugates, like those formed from BP, were degradable with gamma-glutamyltransferase, beta-glucuronidase and arylsulfatase, respectively. Ethyl acetate extractable metabolites were predominantly isomeric benzo-ring tetrahydrotetrols (9% of total metabolites). In summary, this study indicates that during short-term incubations bull-head hepatocytes metabolize BP and BP-7,8-diol primarily to conjugated derivatives. The usefulness of thin-layer chromatography for the convenient determination of the rate of BP-7,8-diol metabolism is demonstrated. PMID- 2322951 TI - Metabolism of 3-hydroxychrysene by rat liver microsomal preparations. AB - 3-Hydroxychrysene, a metabolite of the polycyclic aromatic hydrocarbon (PAH) chrysene, was metabolised by rat liver microsomal preparations obtained from Arochlor 1254-pretreated rats. Eight major metabolites were isolated by high performance liquid chromatography and characterised by u.v. spectroscopy and a variety of mass spectrometric techniques. The metabolites were unambiguously identified as 9-hydroxy-trans-1,2-dihydroxy-1,2-dihydrochrysene and 9-hydroxy-r 1,t-2,t-3,c-4-tetrahydroxy-1,2,3,4-tetrahydrochrysene and tentatively identified as 3-hydroxy-trans-5,6-dihydroxy-5,6-dihydrochrysene (since chrysene is a symmetrical molecule the 3- and 9-positions are equivalent), 9-hydroxy-trans-3,4 dihydroxy-3,4-dihydrochrysene, 1,2,3-trihydroxy-1,2,3,4-tetrahydrochrysene, an oxidised phenol and two diphenols. These results indicate that 3-hydroxychrysene can be further metabolised via a number of different pathways including those involving the formation of phenol- and triol-epoxides. PMID- 2322952 TI - 32P-postlabelling of 7-methyl-dGMP ring-opened 7-methyl-dGMP and platinated dGpdG. AB - The 32P-postlabelling technique introduced by Randerath and coworkers was used to investigate the efficiency of the phosphorylation reaction by T4 polynucleotide kinase using three synthesized adducts: 7-methyl-dGMP, ring-opened 7-methyl-dGMP and platinated dGpdG. The methylated substrates were detected at sub-fmol sensitivities. 7-Methyl-dGMP was quantitatively phosphorylated at these low concentrations. The efficiency of phosphorylation of the ring-opened product was less (about one order of magnitude) and that of Pt(dGpdG) about three orders of magnitude less. These results show that T4 polynucleotide kinase phosphorylation is an efficient reaction with 7-methyl-dGMP and with ring-opened 7-methyl-dGMP, even though in the latter case longer incubation times may have to be used to boost the reaction towards completion. By contrast, the low level of phosphorylation with Pt(dGpdG) does not appear encouraging for quantitative determination requiring a high sensitivity. PMID- 2322953 TI - Interactive inhibition of erythroid 59Fe utilization by benzene metabolites in female mice. AB - Using radioiron uptake into erythrocytes as a measure of hematopoiesis, it was demonstrated that benzene inhibited bone marrow function in female mice. Hydroquinone was marginally effective, but the inhibition occurred only at the highest dose tested (100 mg/kg). The combination of phenol and hydroquinone was more effective in reducing erythrocyte production than either chemical given alone. Catechol given alone was not inhibitory but when phenol was added to catechol, erythropoiesis was suppressed, as observed for the phenol and hydroquinone combination. It appears that benzene toxicity may be the result of cooperative inhibitory effects produced by its metabolites. PMID- 2322955 TI - [Treatment and nursing care in diabetes type I using an ATOM-235 pump intravenous infusion]. PMID- 2322954 TI - The role of hydrophobicity and electronic factors in regulating alcohol inhibition of cytochrome P-450-mediated aniline hydroxylation. AB - The role of hydrophobicity and electronic factors in regulating alcohol inhibition of cytochrome P-450-mediated aniline p-hydroxylation has been investigated by the formulation of quantitative structure-activity relationships. The activity of linear primary alcohols and unhindered linear secondary alcohols shows a linear dependence on log P, where P is the octanol-water partition coefficient. Hindered primary and secondary alcohols are less active than this relationship predicts. An equation describing the activity of both hindered and unhindered primary and secondary alcohols shows that alcohol inhibition of aniline hydroxylation is regulated by hydrophobicity and steric effects. No role for electronic factors can be discerned. Similarities are found between alcohol inhibition and the binding of alkyl amines to cytochrome P-450, suggesting that alcohols may bind to the amine binding site. PMID- 2322956 TI - [Nursing care of low cardiac output syndrome following open heart surgery]. PMID- 2322957 TI - [Dumbbell shaped artificial esophagus replacement surgery care]. PMID- 2322959 TI - [Application of the transfer technique in emotional handling of children on oral medication]. PMID- 2322958 TI - [Effect of drugs on artificial abortion of parous and primiparous women in randomized triple blind method]. PMID- 2322960 TI - [Management of digestive disturbance by Chinese traditional medicine]. PMID- 2322961 TI - [The fully loaded nursing circuit chart in use]. PMID- 2322962 TI - [Nursing care of 50 cases of systemic lupus erythematosus]. PMID- 2322963 TI - [Nursing care of single-layer esophageal anastomosis]. PMID- 2322964 TI - [Postoperative monitoring of corrective transposition of great arteries]. PMID- 2322966 TI - [The scrub nurse's work in open-heart surgery in infants under 2 years of age]. PMID- 2322965 TI - [Nursing care of transplantation of fetal nigra, adrenal medullary tissue for parkinsonism]. PMID- 2322967 TI - [Management of cardiopulmonary bypass in infants and young children]. PMID- 2322968 TI - Total intravenous anaesthesia. PMID- 2322969 TI - Correlation between integrated evoked EMG and respiratory function following atracurium administration in unanaesthetized humans. AB - In six healthy volunteers, integrated evoked electromyography (IEEMG) measured in response to ulnar nerve stimulation was correlated with respiratory function tidal volume (VT), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum negative inspiratory pressure (NIP), hand grip (HG) and head-lift during steady-state infusion of subparalytic doses of atracurium. Studies were carried out at train-of-four T4/T1 = 0.2 and T4/T1 = 0.6. When T4/T1 = 0.2, all subjects had difficulty with swallowing and phonation, none could sustain any head-lift and HG was 26 per cent of control. However, VT was normal, FVC was 80 per cent, FEV1 was 82 per cent, and NIP was 50 per cent of control. AT T4/T1 = 0.6, all assessments of peripheral strength were normal, and all respiratory measurements were not significantly different from control, except for NIP which was 73 per cent of control (P less than 0.05). We conclude that an IEEMG of 0.6, recorded from the hypothenar muscles, in unanaesthetized subjects is consistent with near normal respiratory function. PMID- 2322970 TI - Fluid through the epidural needle does not reduce complications of epidural catheter insertion. AB - Epidural catheter insertion may be associated with blood vessel trauma or nerve root irritation. The purpose of this study was to assess whether the injection of small amounts of fluid through the Tuohy needle prior to catheter insertion reduced the incidence of these and other minor complications. Two hundred patients in labour, requesting epidural analgesia, were randomly assigned to one of three groups: Group I--the catheter was inserted without previous injection of fluid; Group II--3 ml, 1.5 per cent lidocaine hydrochloride was injected through the needle prior to catheter insertion; Group III--3 ml, saline was injected prior to catheter insertion. There were no differences among the groups in the incidence of blood vessel trauma or paraesthesiae. We conclude that there is no advantage in injecting of fluid routinely into the epidural space prior to catheter insertion. PMID- 2322971 TI - Epidural anaesthesia for transurethral resection of the prostate in a patient with carcinoid syndrome. AB - The anaesthetic management of a 63-year-old patient with carcinoid syndrome presenting for transurethral resection of the prostate (TURP) is described. Before surgery antibradykinin, antiserotonin and antihistamine drugs were used in addition to SMS 201-995, a long-acting somatostatin analogue, to prevent the intraoperative release of hormones associated with this syndrome. Several techniques of general anaesthesia have achieved successful patient outcomes. Monitoring included pulse oximetry and radial artery cannulation. After infusion of Ringer's lactate, 750 ml, and 25 per cent albumin, 150 ml, an incremental epidural block with xylocaine two per cent without adrenaline was administered to achieve ideal operating conditions without any change in haemodynamic variables or oxygen haemoglobin saturation. Epidural anaesthesia seems to be a safe alternative to general anaesthesia in patients with carcinoid syndrome presenting for TURP. PMID- 2322972 TI - Cervical epidural anaesthesia for carotid artery surgery. AB - A series of 394 patients (251 men, 143 women; mean age 70.0 +/- 8.4 yr) selected for carotid artery surgery (CAS) performed under cervical epidural anaesthesia (CEA) was analysed retrospectively. Carotid endarterectomy was performed in 326 patients and saphenous vein bypass in 68. The cervical epidural administration of 15 ml 0.5 per cent bupivacaine or 0.37-0.40 per cent bupivacaine plus fentanyl (50-100 micrograms) resulted in an effective sensory blockade from C2 to T4-T8. Patients were maintained awake during the surgical procedure in comfortable condition. Serious complications included dural puncture in two patients, epidural venipuncture in six patients and respiratory muscle paralysis in three patients. Hypotension (10.9 per cent) and bradycardia (2.8 per cent) were the most frequent side-effects of CEA. Transient neurological events were noticed in 84 patients during the surgical procedure. A definite neurological deficit occurred postoperatively in 12 patients. Three patients suffered postoperative myocardial infarction. The mortality rate was 2.3 per cent (nine patients). Carotid artery surgery may be performed under CEA but haemodynamic variables should be monitored closely and managed closely during the procedure. PMID- 2322973 TI - Lumbar and thoracic epidural analgesia via the caudal approach for postoperative pain relief in infants and children. AB - Thirty infants scheduled for a variety of gastrointestinal, genitourinary and thoracic surgical procedures were selected for insertion of lumbar or thoracic epidural catheters via the caudal approach using either an Intracath or a Burron continuous brachial plexus kit. The catheters were inserted with ease by residents in training and no catheter-related complications were encountered. Lidocaine 0.5 per cent with 1:200,000 epinephrine was then injected to assure proper placement of the catheter before narcotics were administered. Postoperative analgesia was adequate in all patients using preservative-free morphine 0.05 mg.kg-1. The mean dosing interval was 15 hr and no episodes of nausea, vomiting, hypotension or histamine release were noted. Urinary retention occurred in two infants and one infant became apnoeic three hours after epidural morphine administration but responded to naloxone and pulmonary ventilation with bag and mask. In conclusion, epidural catheters placed via the caudal approach are a safe and effective means of providing postoperative pain control in infants using preservative-free morphine. However, the use of epidural narcotics in infants less than two years of age is restricted to those who will receive intensive care unit monitoring postoperatively so that if apnoea occurs, rapid intervention can be taken by skilled nursing personnel. PMID- 2322974 TI - Respiratory inductance plethysmography and pulse oximetry in the assessment of upper airway patency in a child with Goldenhar's syndrome. AB - The anaesthetic management of a child with Goldenhar's syndrome and upper airway dysmorphology is presented. She had a history of severe dyspnoea due to deterioration of cor pulmonale caused by upper airway obstruction. The patency of the upper airway and oxygenation were evaluated during the perioperative period with respiratory inductive plethysmography (RIP) and pulse oximetry, which did not show severe upper airway obstruction or oxygen saturation below 80 per cent. Tracheal intubation was performed under inhalational anaesthesia with spontaneous breathing. This case suggests that RIP and pulse oximetry may be useful monitoring devices in the anaesthetic management of patients with upper airway problems as in Goldenhar's syndrome. PMID- 2322976 TI - Brain circuit delivery tube obstructions. PMID- 2322975 TI - Congenital lobar emphysema. AB - This paper reviews three cases of congenital lobar emphysema from Saudi Arabia, seen over a period of three years. All were boys aged 2.5, 7 and 8 months, and recurrent attacks of chest infection, which started during the early neonatal period, were the main presentation. In all cases, diagnosis was confirmed by chest x-ray. Two of them had a lobectomy and made a good recovery. Operation was refused in the third. The clinicopathological features, diagnosis and management are discussed. An outline of the anaesthetic management is also discussed briefly. PMID- 2322977 TI - Continuous subcutaneous injection of ketamine for cancer pain. PMID- 2322978 TI - Anaesthetic data logging using a Psion pocket computer. PMID- 2322979 TI - Failed intubation. PMID- 2322980 TI - Pulmonary artery catheter failure. PMID- 2322981 TI - Rate-pressure product. PMID- 2322982 TI - Anaesthesia and medico-legal concerns. PMID- 2322983 TI - Epidural air-filled bubbles and unblocked segments. PMID- 2322984 TI - Surgery in Jehovah's Witnesses. PMID- 2322985 TI - Cycloheximide-induced modulation of TNF-mediated cytotoxicity in sensitive and resistant ovarian tumor cells. AB - The mechanism of sensitivity and resistance of various ovarian carcinoma lines to recombinant tumor necrosis factor (rTNF)-mediated cytotoxicity has been investigated using a 24-h 51Cr-release assay. The cell line PA-1 is sensitive to TNF in a dose-dependent manner, whereas the cell line SKOV-3 is resistant to TNF even at high concentrations. The simultaneous addition of TNF and cycloheximide (CHX) in the assay converted the resistant SKOV-3 line into a sensitive line, but no detectable change was observed with PA-1. rTNF inhibited DNA, RNA, and protein synthesis of the sensitive PA-1 line, whereas it had no effect on SKOV-3. This finding was not due to differences in the expression of TNF receptors, as both cell lines expressed equivalent numbers of receptors. The addition of CHX to TNF resulted in suppression of DNA, RNA, and protein synthesis in both the sensitive and the resistant cell lines. Pretreatment of the cell line with TNF for 3 h and subsequent washing resulted in significant cytotoxicity of the sensitive PA-1 line and some cytotoxicity against SKOV-3. However, if the cells were pretreated with CHX for 3 h followed by rTNF for 24 h, a significant decrease in cytotoxicity was observed in both cell lines. Under these conditions, there was no significant inhibition of DNA, RNA, or protein synthesis. Pretreatment of cells for 24 h with TNF and 24 h with CHX resulted in augmentation of the cytotoxicity of PA-1 and SKOV-3, whereas pretreatment for 24 h with CHX followed by 24 h with TNF resulted in no cytotoxicity. Cells pretreated with CHX for 24 h showed poor binding of [125]I-TNF and poor internalization, whereas cells pretreated for 24 h with TNF showed marked enhancement of internalization. The sensitivity of freshly derived ovarian carcinoma lines to TNF and CHX demonstrated that TNF-resistant cells became more sensitive if treated with CHX. These results demonstrate the potential use of metabolic inhibitors in increasing the sensitivity of fresh ovarian tumor cells to TNF. PMID- 2322986 TI - Tissue distribution of doxorubicin associated with polyisohexylcyanoacrylate nanoparticles. AB - The body distribution of i.v. doxorubicin depends mainly on the physicochemical characteristics of the molecule. However, entrapment of that cytostatic drug inside polyalkylcyanoacrylate nanoparticles has been shown to modify its distribution profoundly in the mouse. Polysiohexylcyanoacrylate nanoparticles loaded with [14C]-doxorubicin were studied in comparison with free drug, with emphasis on their distribution pattern in mouse tissue after i.v. administration. An autoradiographic study showed that most of the radioactivity was found in the reticuloendothelial system as soon as a few minutes after i.v. administration of the doxorubicin-loaded nanoparticles. Quantitative determinations by liquid scintillation counting in fresh tissue (spleen, heart, kidneys, liver, lungs, bone marrow) and blood samples confirmed these observations. When the drug was linked to nanoparticles, doxorubicin blood clearance was reduced during the first few minutes after administration, whereas heart and kidney concentrations were substantially decreased. Assays of doxorubicin and doxorubicinol by a specific HPLC analytical method gave results very similar to those obtained by scintillation counting. PMID- 2322987 TI - Triple combination of retinoic acid plus actinomycin D plus dimethylformamide induces differentiation of human acute myeloid leukaemic blasts in primary culture. AB - Differentiation induction therapy provides an alternative for treatment of acute myeloid leukaemia (AML) patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + actinomycin D (Act-D) + dimethylformamide (DMF) on differentiation of blasts from 24 AML patients was studied. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in 24-well tissue-culture plates containing RPMI 1640 culture medium with 20% fetal calf serum, 10% autologous serum and 10% 5637-conditioned medium and incubated with 10(-6) M retinoic acid, 5 nM actinomycin D and/or 100 mM dimethylformamide alone and in combination with each other for 6 days at 37 degrees C in a humidified incubator and an atmosphere containing 5% CO2. The triple combination of 10(-6) M retinoic acid + 5 nM actinomycin D + 100 mM dimethylformamide induced 90% of the blasts from 22 of the 24 AML patients to differentiate. The combination of N methylformamide (a compound similar to dimethylformamide) with cyclophosphamide significantly increased the in vivo activity with no concomitant increase in its reversible hepatotoxicity. Since several polar compounds related to dimethyl formamide, e.g. hexamethylene bisacetamide and N-methylformamide, are currently undergoing phase II clinical trials, it may be feasible to combine one of these with retinoic acid and/or actinomycin D in the treatment of AML patients. PMID- 2322988 TI - Efficacy of ganglioside treatment in reducing functional alterations induced by vincristine in rabbit peripheral nerves. AB - Vincristine (VCR) administration to rabbits resulted in severe electrophysiologic alterations of peripheral nerves. Sciatic nerve conduction velocity, compound action potential (CAP) amplitude, and area under the CAP waveform were all reduced in a dose-dependent fashion. In addition, the pattern of conduction velocity of both motor and sensory fibers was altered and shifted toward slow conduction classes. Simultaneous treatment with gangliosides limited significantly the changes in electrophysiologic parameters induced by VCR. It is suggested that gangliosides be given in the clinical setting as protection for the peripheral nerves against the side effects of antiblastic therapy. PMID- 2322989 TI - Enhancement of cisplatin (DDP) antitumor activity by 3-aminobenzamide in rat ovarian tumors sensitive and resistant to DDP in vivo. AB - A cisplatin (DDP)-resistant rat ovarian tumor cell line (O-342/DDP) and its parental sensitive counterpart (O-342) were used to investigate the combination effect of DDP plus 3-aminobenzamide (3-AB), an inhibitor of adenosine diphosphate ribose transferase (ADPRT). Treatment with six doses of DDP in NMRI nude mice bearing O-342/DDP produced an increase in mean survival of only 1 day over that of controls (P less than 0.05). The addition of nontoxic doses of 3-AB (5 mM/kg x 6) increased the mean survival to 6.4 days compared with that obtained with DDP treatment alone (P less than 0.001). In the sensitive ovarian tumor line (O-342), the combination effect of DDP plus 3-AB was even more impressive: simultaneous treatment of NMRI nude mice bearing O-342 with three doses of DDP plus 3-AB increased the mean survival by 2 weeks and the median survival by 3 weeks over that achieved with DDP treatment alone. Possible mechanisms involved in the potentiation of DDP activity and the possible clinical potential of this combination are discussed. PMID- 2322990 TI - Flavone acetic acid distribution in human malignant tumors. AB - The pharmacokinetics of flavone acetic acid (FAA) after a dose of 4.8 mg/m2 given i.v. over 1 h was investigated in 13 patients with different solid tumors. The mean volume of distribution and clearance were 52 +/- 4 l/m2 and 2.6 +/- 0.2 l/h x m2, respectively. A tumor or metastasis biopsy was obtained from six patients 2 h after the end of infusion. Tumor FAA levels ranged from 39.6 to 148.8 micrograms/g and were similar to those obtained after a therapeutic i.v. dose of 200 mg/kg FAA in animals bearing Pan/03 tumor, which is very sensitive to the drug. Although FAA tumor concentration could be detected only during one interval and we therefore cannot draw a definitive conclusion, differences in the agent's antitumor activity in mice and patients (i.e. very active in the former and inactive in the latter) are apparently not due to discrepancies in drug distribution and pharmacokinetics. PMID- 2322991 TI - Treatment of advanced breast cancer in postmenopausal women with 4 hydroxyandrostenedione. AB - 4-Hydroxyandrostenedione (4-OHA), a new specific aromatase inhibitor, was used to treat 57 postmenopausal women with advanced breast cancer at a dose of 250 mg by i.m. injection every 2 weeks; 55 women were assessable for response. In all, 18 patients (33%) had objective evidence of a response to treatment, with a median duration of 12 months; the disease stabilised in 8 (14%) patients. Serum oestradiol levels, which were measured weekly in nine of the patients, were found to be suppressed to a mean of between 36% and 51% of pretreatment levels during the first 6 weeks of treatment. Three patients were withdrawn from treatment because of toxicity (pain at injection site, sterile abscess and rash). One patient had an isolated episode of anaphylaxis after 6 months of treatment. In comparison with our previous reports of 4-OHA treatment, a dose of 250 mg given i.m. fortnightly appears to be the optimal dose regimen. The efficacy of the drug seems to be similar to that of tamoxifen and aminoglutethimide. PMID- 2322992 TI - Differential cytotoxicity of combretastatins A1 and A4 in two daunorubicin resistant P388 cell lines. AB - Combretastatin A4, a novel anti-mitotic agent was effective against two P388 cell lines with acquired resistance to daunorubicin. In contrast, Combretastatin A1, a close structural analogue of A4, showed a high degree of cross-resistance. Combretastatin A1 was also more efficient at increasing intracellular daunorubicin concentrations in both resistant cell lines. Neither agent was capable of altering anthracycline accumulation in the parental (sensitive) cell line. We propose that the cross-resistance to Combretastatin A1 occurs, at least in part, as a result of the increased affinity of the drug-efflux process operative in these resistant cells for Combretastatin A1 vs Combretastatin A4. Hence, Combretastatin A4 may play a role in the treatment of tumours with acquired resistance to the anthracycline antibiotics. PMID- 2322993 TI - Comparative metabolism and pharmacokinetics of doxorubicin and 4'-epidoxorubicin in plasma, heart and tumor of tumor-bearing mice. AB - Epidoxorubicin, a stereoisomer of doxorubicin, shows comparable antitumor activity but diminished cardiotoxicity compared with the latter. To find a pharmacokinetic basis for the observed difference in cardiotoxicity between the drugs, concentrations of doxorubicin, epidoxorubicin and all known metabolites were measured in the plasma, heart and tumor tissue of BALB/c mice bearing colon 26 tumors. Both drugs were injected at the same dose (10 mg/kg) as an i.v. bolus. Plasma, heart and tumor samples were obtained from two mice sacrificed at regular intervals over 48 h. Plasma and tissue extracts were analyzed by HPLC with fluorescence detection. The parent compounds and the two 7d-aglycones were present in all three compartments, whereas doxorubicinol (Aol) and epidoxorubicinol (Eol) could only be detected in the plasma and heart. Half-lives and AUCs of doxorubicin and its metabolites were higher than the corresponding values for epidoxorubicin and its metabolites in all three compartments. PMID- 2322994 TI - Study of various transforming effects of the anabolic agents trenbolone and testosterone on Syrian hamster embryo cells. AB - Trenbolone, a synthetic androgen together with testosterone, a natural androgen, were studied comparatively for their transforming effects on Syrian hamster embryo (SHE) cells. The data indicated that both androgens exhibited weak positive complete transforming activities without a dose response relationship. Trenbolone is more toxic than testosterone when the concentrations tested are higher than 10 micrograms/ml, but is less able to transform SHE cells. Medium H21 offers a higher transformation frequency than medium H16. Their transforming effect can be amplified by TPA. However, both products can also reduce the transforming effect of benzo[a]pyrene (B[a]P) either in sequential treatment or when mixed together. The transforming effects of the two androgens including TPA effects can be inhibited completely by dexamethasone, which suggests that such transformation in SHE cells is an epigenetic effect. In conclusion, trenbolone and testosterone themselves exhibit a weak transforming effect on SHE cells, predominantly as promoting potential, especially when associated with 12-O tetradecanoyl-phorbol-13-acetate, which is related to hormonal action. They also exhibit weak anti-transforming effects when associated with B[a]P. PMID- 2322995 TI - Comparison of initiation potential of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in an in vivo carcinogen bioassay system. AB - A new approach to low-dose assessment of carcinogenic potential was applied to food contaminant pyrolysis products. Single intragastric doses of the carcinogenic pyrolysates, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino 3,8-dimethylimidazo[4,5-f]quinoxaline MeIQx), were given 12 h after two-thirds partial hepatectomy (PH) to F344 male rats. Two weeks thereafter the animals were placed on a basal diet containing 0.05% phenobarbital (PB) for 6 weeks combined with an i.p. administration of D-galactosamine (300 mg/kg) to facilitate growth of initiated cells. Both IQ and MeIQx clearly caused initiation of hepatocarcinogenesis as revealed by induction of preneoplastic placental-form glutathione-S-transferase-positive (GST-P+) hepatocyte foci composed of more than three cells (approximately 30 microns in diameter). A similar protocol without performance of PH before pyrolysate administration gave a positive result only for the IQ-treated group indicating that cell proliferation is essential during the low-dose, one-shot initiation step. IQ was found to be two to three times more potent in inducing GST-P+ foci using both protocols. The current approach could find application in practical carcinogenicity screening of chemicals, for which only small amounts are available. PMID- 2322996 TI - Synchronous fluorescence spectroscopic, immunoaffinity chromatographic and 32P postlabeling analysis of human placental DNA known to contain benzo[a]pyrene diol epoxide adducts. AB - Human placenta readily catalyzes the biotransformation of polycyclic aromatic hydrocarbons (PAHs) and other carcinogens to reactive metabolites that can damage DNA through formation of covalent adducts. Placenta is widely available for epidemiologic studies and may be a useful dosimeter for carcinogen exposures in humans. However, previous studies of human placental DNA have yielded discrepant results with respect to PAH-DNA adducts. In order to resolve some of the issues surrounding these discrepancies, placental DNA samples known to contain benzo[a]pyrene diol epoxide adducts were also analyzed by 32P-postlabeling and immunoaffinity chromatography. Results indicate that previous discrepancies can be accounted for by methodologic factors affecting the specificities of adduct assays in biological samples and suggest that human placental DNA contains adducts derived from multiple PAHs. PMID- 2322997 TI - Correlation between medium-term liver bioassay system data and results of long term testing in rats. AB - The effects of hepatocarcinogens (ethionine, thioacetamide, phenobarbital), non hepatocarcinogens [N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN), N-methyl-N' nitro-N-nitrosoguanidine (MNNG)] and a hepatoinhibitor [(butylated hydroxyanisole (BHA)] were compared in medium- and long-term in vivo systems. In experiment I, 2 weeks after a single injection of diethylnitrosamine (DEN) groups of male F344 rats received chemical administration for 6 weeks, combined with partial hepatectomy at week 3 and were killed at the end of week 8. In experiment II, animals were treated in the same manner and then given basal diet and tap water (group 1) or chemical continuously (group 2) until the 2 year timepoint. Numbers and areas of glutathione S-transferase placental form (GST-P)-positive foci developing in the liver under medium-term bioassay conditions (experiment I) were found to closely correlate with eventual hepatocellular carcinoma incidences after continuation of test chemical administration (experiment II). Thus all of the hepatocarcinogens enhanced both the induction of GST-P-positive focal lesions and liver tumors. While non-hepatocarcinogens exerted no such effects, their influence being limited to inducing lesions in their own respective target organs such as urinary bladder cancers in the EHBN case and glandular stomach adenocarcinomas with MNNG, BHA demonstrated inhibition potential in both experiments. The observed correlation between long- and medium-term results strongly indicates the applicability of our medium-term bioassay system for detection of liver carcinogens. PMID- 2322998 TI - Disparate cytogenetic responses of peripheral blood and spleen lymphocytes to ethenoadenine nucleotides in vitro; maximal expression in splenic lymphocytes under conditions of enhanced membrane permeabilization. AB - Exogenously supplied 1,N6-ethenoadenosine triphosphate (epsilon-ATP) and 1,N6 ethenodeoxyadenosine triphosphate (epsilon-dATP) are potent inducers of sister chromatid exchanges (SCEs) in murine spleen lymphocytes but not in peripheral blood lymphocytes cultured in vitro. Data suggest that spleen lymphocyte membranes are inherently more permeable than blood lymphocytes to transient uptake of epsilon-ATP and epsilon-dATP. The effect of media pH and divalent cations on SCE frequency and chromosomal aberrations in spleen cells pulse treated with epsilon-ATP were studied. The most dramatic responses were observed at pH 8.0 in Ca2+/Mg2(+)-free Hank's balanced salt solution (HBSS). Under the latter conditions, SCE and chromosomal aberration responses (mean +/- SD) of lymphocytes from replicate mice were 69.4 +/- 13.1 SCE/cell and 49 +/- 8.5% of cells with aberrations respectively. Chromosomal aberrations included multiple complex breakage and rearrangements. In HBSS containing Ca2+ (0.575 mM) and Mg2+ (0.4 mM) in concentrations equivalent to those in RPMI 1640, maximum SCE and aberration responses of 31.8 and 28% were observed in cells treated at pH 6.0. Similarly, maximum SCE frequencies (46 +/- 1.6 SCE/cell) and percentage of cells with aberrations (8 +/- 1.4%) were present in spleen cells treated at pH 6.0 in RPMI media. SCEs and aberrations decreased with increasing pH in either media containing divalent cations. In Ca2+/Mg2(+)-free HBSS, the highest mitotic index and fastest cell cycling were seen at pH 6.0. Mitotic indices dropped dramatically at pH 7.4 but recovered considerably at pH 8.0, in spite of a high frequency of cells containing aberrant chromosomes. The most dramatic cytotoxicity occurred at pH 6.0 in HBSS containing Ca2+ and Mg2+. Decreased cytotoxicity was apparent at higher pH and in RPMI medium. Conditions for optimal growth of control cells were obtained following pulse-treatment in Ca2+/Mg2(+) free HBSS medium at high pH (8.0). Because of the dramatic cytogenetic toxicity of exogenously supplied epsilon-ATP, and the ubiquitous occurrence and biological importance of intracellular ATP, the latter should be considered a potential target for adduct formation by electrophilic metabolites of carcinogenic agents. PMID- 2322999 TI - Effect of resiniferatoxin pretreatment on the inflammatory response to phorbol-12 myristate-13-acetate in mouse strains with different susceptibilities to phorbol ester tumor promotion. AB - All tumor-promoting phorbol esters induce inflammation in mouse skin. The correlation between promoting and inflammatory activities is only partial, however, indicating that only some events in inflammation may be closely coupled to the process of tumor promotion. Resiniferatoxin (RTX), an extremely inflammatory phorbol-related diterpene, acts as an ultrapotent analog of capsaicin to stimulate and then to block the neurogenic inflammatory pathway. In CD-1 mice, we have used pretreatment with RTX to show that the erythema and edema responses to phorbol and 12-deoxyphorbol esters in significant part involve this neurogenic inflammatory pathway. We report here that mouse strains with differing sensitivities to phorbol-ester-induced promotion displayed marked differences in the effect of pretreating with RTX on the edema response following phorbol-12 myristate-13-acetate (PMA) application. In the highly promotion-sensitive SENCAR mouse, RTX pretreatment had little inhibitory effect; the edema response to PMA was similar with or without RTX pretreatment 6 h before PMA application. On the other hand, in C57BL/6J mice, which are resistant to promotion by phorbol esters under the usual protocols, the edema response to PMA was totally eliminated by RTX pretreatment during the first 8 h after PMA administration. DBA/2J mice, which are similar to CD-1 mice in their susceptibility to PMA promotion, responded similarly to CD-1: the edema response was blocked partially by RTX pretreatment during the early phase (up to 8 h) of inflammation. Our results suggest that the RTX-resistant component of PMA-induced edema may correlate better with the sensitivity to promoting action than does the overall inflammatory response. PMID- 2323000 TI - Partial hepatectomy is a promoter of hepatocarcinogenesis in C57BL/6J male mice but not in C3H/HeJ male mice. AB - We have shown previously that the difference between C57BL/6J and C3H/HeJ male mice in their susceptibilities to chemically-induced liver tumors results predominantly from an allelic difference at the Hepatocarcinogen sensitivity (Hcs) locus. This locus modulates the rate of growth of preneoplastic liver lesions and may also play a role in the turnover of normal hepatocytes in the adult liver. To define further the growth regulatory pathway of which the Hcs gene is a component, we asked whether the expression of the Hcs gene would modulate the response of preneoplastic liver lesions to the physiologic growth stimulus generated by a two-thirds hepatectomy. Twelve-day-old male and female C57BL/6J and C3H/HeJ mice were injected with 0.5 mumols N-ethyl-N-nitrosourea/g body weight. At six weeks of age half the animals received a two-thirds hepatectomy. Groups of animals were killed between 14 and 44 weeks of age for analysis of glucose-6-phosphatase (G6Pase)-deficient foci and hepatic tumors. The partial hepatectomy induced a regenerative response that caused both the G6Pase deficient foci and the surrounding, histochemically normal hepatocytes to undergo several rapid rounds of division. As a result, the G6Pase-deficient foci were larger in the hepatectomized animals than in the sham operated controls. The foci in the non-hepatectomized C57BL/6J male mice grew more slowly than in the C3H/HeJ male mice [volume doubling time (Td) = 2.9 +/- 0.1 weeks and 2.0 +/- 0.6 weeks, respectively]. Following partial hepatectomy, the G6Pase-deficient foci in the C57BL/6J male mice maintained a significantly higher growth rate (Td = 2.2 +/- 0.3 weeks) than the foci in the sham operated C57BL/6J male mice. The partial hepatectomy did not have any long term effect on the growth rate of the G6Pase deficient foci in the C3H/HeJ male mice nor in female mice of either strain. At 32 weeks of age, the mean liver tumor multiplicity for hepatectomized C57BL/6J male mice was approximately 5.3-fold greater than that for sham operated animals. In contrast, a two-thirds hepatectomy resulted in a 60% reduction in the number of liver tumors in C3H/HeJ male mice relative to sham operated mice. These data demonstrate that partial hepatectomy can act as a promoter of hepatocarcinogenesis in C57BL/6J male mice but not C3H/HeJ male mice. We propose that the Hcs gene and partial hepatectomy may promote hepatocarcinogenesis through the same pathway of growth regulation. PMID- 2323001 TI - Malignant transformation of mouse BALB/c3T3 cells induced by NaNO2. AB - The addition of sodium nitrite (NaNO2; 5-20 mM) for 72 h to mouse BALB/c3T3 cells resulted in the induction of transformed foci (type III foci) in a dose-dependent manner. The cells isolated from the NaNO2-induced transformed foci produced progressively growing tumors when inoculated into nude mice subcutaneously at an inoculum size of 1 X 10(6) cells per site. In contrast, the original untreated cells did not take even at an inoculum size of 1 X 10(7) cells per site. The possibility that NaNO2 might react with cellular or medium components to make carcinogenic N-nitrosamines and that these might induce cell transformation was examined and almost excluded. Thus, nitrite itself seems to have a cell transforming activity. Recent evidence suggests that NO2- is produced by the activated macrophages of mammals. We also detected NO2- production in culture media in the mouse macrophage-like cell line J774-A1 after lipopolysaccharide (LPS) treatment, and also in the human promyeloleukemia cell line HL60 after differentiation into macrophage-like cells by 12-O-tetradecanoyl phorbol-13 acetate and further activation by LPS. PMID- 2323002 TI - Detection and characterization of carcinogen-DNA adducts in exfoliated urothelial cells from 4-aminobiphenyl-treated dogs by 32P-postlabelling and subsequent thin layer and high-pressure liquid chromatography. AB - The recent development of sensitive methods to detect carcinogen-DNA adducts offers a useful biochemical approach to human risk assessment. However, a major obstacle to developing a human biomonitoring method for carcinogen-DNA adducts has been the problem of obtaining target tissue DNA samples by non-invasive means. This work describes a method for the isolation of nanogram quantities of DNA from urothelial cells exfoliated into urine and the detection of carcinogen DNA adducts from that DNA by 32P-postlabelling methods. Urine samples were collected on ice from dogs treated with 4-aminobiphenyl (ABP) over a 2-week period and pooled according to an experimental plan that involved analysis of cumulative 48- or 72-h samples. The pooled samples were sieved and then washed repeatedly with a sucrose buffer to dissolve contaminating triple phosphate (MgNH4PO4), calcium oxalate and uric acid crystals. DNA was isolated using an enzyme-solvent extraction method with the DNA being co-precipitated from ethanol with glycogen. The DNA was hydrolysed and postlabelled with 32P under conditions of excess ATP so that nucleotides were labelled quantitatively. Adducts observed on the resulting thin-layer chromatograms were identical to those obtained from DNA modified in vitro with N-hydroxy-4-aminobiphenyl and from dog bladder urothelial DNA isolated from the ABP-dosed animals at termination of the experiment. Furthermore, a dose-related increase in ABP-DNA adduct formation was demonstrated. Thus, it appears that the carcinogen-DNA adduct levels in the exfoliated bladder cells are reflective of the levels in the intact urothelium once steady-state levels have been achieved. To establish the identity of the major ABP-urothelial DNA adduct in chronically-treated dogs, the predominant 32P postlabelled adduct was eluted from the thin-layer chromatograms and co-injected on an HPLC system with a synthetic [3H]N-(deoxyguanosin-8-yl)-4-aminobiphenyl 3',5'-bisphosphate standard. Dual-label analysis of 3H and 32P indicated that both eluted from the column in the same fraction, which coincided with the UV absorbance peak of the synthetic marker. Preliminary experiments with exfoliated urothelial cells from human urines indicate that these methods should have general utility for monitoring humans exposed to urinary bladder carcinogens and for investigations of the biochemical mechanisms by which such adducts are formed in the urothelium. PMID- 2323003 TI - Initiation by nickel acetate and promotion by sodium barbital of renal cortical epithelial tumors in male F344 rats. AB - Soluble nickel(II) ion, given to male F344/NCr rats as a single i.p. injection of nickel(II) acetate tetrahydrate at a dose of 90 mumols/kg body weight at 5 weeks of age, proved an effective initiator of renal cortical epithelial tumors. The tumors were revealed by subsequent dosing with the known renal tumor promoter, sodium barbital (5,5-diethylbarbituric acid, sodium salt) dissolved in drinking water at a concentration of 500 p.p.m. Only one rat given the nickel injection without subsequent promotion developed a single renal cortical adenoma, while multiple tumors were common in nickel(II) initiated/sodium barbital promoted rats. Renal cortical adenocarcinomas, some of them metastatic to lung, liver, and spleen, occurred only in initiated/promoted rats. No excess incidence of nickel initiated tumors was found in any other tissues in which sodium barbital is known to promote carcinogenesis, such as liver or thyroid. A single i.p. injection of the Ni(II) salt, 95 mumols/kg, appeared to be associated with an increased concentration of 8-hydroxy-2'-deoxyguanosine in DNA extracted from kidneys of rats 16-48 h after injection. PMID- 2323004 TI - Immunohistochemical demonstration of carcinogen-DNA adducts in target and non target tissues of rats given a prostate carcinogen, 3,2'-dimethyl-4 aminobiphenyl. AB - An immunohistochemical procedure was applied which allows accurate localization of DNA lesions within organs and tissues of rats given 3,2'-dimethyl-4 aminobiphenyl (DMAB) using polyclonal antibodies against DMAB-DNA adducts. Dose related nuclear staining was observed in organs regardless of DMAB-carcinogenic organotropism. In the male accessory sex organs, the lateral lobe of the prostate, a non-target site, demonstrated a similar staining intensity to that found for the ventral prostate and seminal vesicle, target sites. Orchiectomy and pretreatment with ethinyl estradiol resulted in a moderate to slight decrease in binding in the accessory sex organs. No observable decrease in staining intensity was evident in most organs 168 h after the administration of DMAB. These findings suggest that DNA adduct formation itself is not necessarily sufficient for tumor induction. PMID- 2323005 TI - Both tumour-promoting and non-promoting phorbol esters inhibit [125I]EGF binding and stimulate the phosphorylation of an 80 kd protein kinase C substrate protein in intact quiescent swiss 3T3 cells. AB - Sapintoxin A (SAP A) and 12-deoxyphorbol 13-phenylacetate (DOPP), are two biologically active but non-tumour-promoting phorbol esters that potently bind to and activate the phorbol ester receptor, protein kinase C (PKC). SAP A and DOPP cause a dose-dependent increase in the phosphorylation of an 80 kd (80K) substrate protein for PKC in Swiss 3T3 cells. A similar dose-response effect was seen with sapintoxin D (SAP D), the stage 2 promoting analogue of 12-O tetradecanoylphorbol-13-acetate and the complete promoter phorbol 12,13 dibutyrate (PDB). The doses resulting in a half maximal phosphorylation of this protein (Ka) were 20 nM (SAP A), 45 nM (DOPP), 23 nM (SAP D) and 37 nM (PDB). Both non-promoting and promoting phorbol esters induced a dose-dependent inhibition of [125I]epidermal growth factor (EGF) binding to its receptor in Swiss 3T3 cells. The doses required for 50% inhibition of binding (Ki) were: 8 nM (SAP A), 16 nM (DOPP), 14 nM (SAP D) and 17 nM (PDB). The results clearly demonstrate that induction of phosphorylation of the 80K phosphoprotein and inhibition of [125I]EGF binding in Swiss 3T3 cells following exposure to phorbol esters is independent of the tumour-promoting activity of these compounds. The fact that SAP A, DOPP, SAP D and PDB are mitogenic for a variety of cell types and that exposure to these compounds leads to 80K phosphorylation and inhibition of [125I]EGF binding, suggests that these early biological events may play a role in the mitogenic response induced by these compounds. PMID- 2323006 TI - Asbestos-related malignant mesothelioma: growth, cytology, tumorigenicity and consistent chromosome findings in cell lines from five patients. AB - Seven mesothelioma cell lines were established from clinical specimens from five patients with asbestos-related malignant pleural mesothelioma. The cells in culture show either epithelial or mixed epithelial/fibrosarcomatous growth with an average doubling time of 30 h. Giant multinucleated cells are common in all the cell lines, as well as long thin microvilli on the cell surfaces. All cell lines were cytokeratin positive and they stained negatively for monocyte macrophage markers. All seven cell lines and one long-term tissue culture from a sixth mesothelioma patient were characterized cytogenetically. Karyotype analyses revealed complex structural and numerical abnormalities, primarily involving chromosome 1, 4, 5, 6, 7, 8, 9, 11, 12, 13 and 22. An excess of chromosome material of the short arm of chromosome 5 was seen consistently in six cell lines and in the long-term culture. In cell lines from four patients, changes in chromosome 13, mainly monosomy 13, were observed. The marker chromosomes observed in the early passages were conserved and few additional changes appeared in later passages. Six of the cell lines tested for tumorigenicity in athymic nude mice were weakly positive. PMID- 2323007 TI - 32P-postlabeling assay for carcinogen-DNA adducts: description of beta shielding apparatus and semi-automatic spotting and washing devices that facilitate the handling of multiple samples. AB - The utilization of the 32P-postlabeling assay in combination with TLC for the sensitive detection and estimation of aromatic DNA adducts has been increasing in the past few years. The procedure consists of 32P-labeling of carcinogen-adducted 3'-nucleotides in the DNA digests using [gamma-32P]ATP and polynucleotide kinase, separation of 32P-labeled adducts by TLC, and their detection by autoradiography. During both 32P-labeling and initial phases of TLC, a relatively high amount of [gamma-32P]ATP (3.0-4.5 mCi) is handled when 30 samples are processed simultaneously. We describe the design of acrylic shielding apparatus, semi automatic TLC spotting devices, and devices for development and washing of multiple TLC plates, which not only provide substantial protection from exposure to 32P beta radiation, but also allow quick and easy handling of a large number of samples, thus expediting the assay workup and making it less labor-intensive. Specifically, the equipment includes: (i) a multi-tube carousel rack (7.5 cm diameter and 7.7 cm height) having 15 wells to hold capless Eppendorf tubes (0.5 ml) and a rotatable lid with an aperture to access individual tubes; (ii) a pipet shielder; (iii) two semi-automatic spotting devices to apply radioactive solutions to TLC plates; (iv) a multi-plate holder for TLC plates; and (v) a mechanical device for washing multiple TLC plates. Item (i) is small enough to be held in one-hand, vortexed, and centrifuged to mix the solutions in each tube while beta radiation is shielded. Items (iii) to (iv) aid in the automation of the assay. PMID- 2323008 TI - 9,10-Dihydroxy-9,10-dihydro-3-methylcholanthrene-2-one: a principal metabolite of the potent carcinogen 3-methylcholanthrene-2-one by rat liver microsomes. AB - A principal metabolite, formed in the metabolism of the potent carcinogen 3 methylcholanthrene-2-one (3MC-2-one) by liver microsomes from either untreated, or phenobarbital-treated or 3-methylcholanthrene (3MC)-treated rats, was isolated by reversed-phase HPLC. This metabolite has been identified as a 9,10-dihydrodiol with a (9R,10R):(9S,10S) enantiomer ratio of approximately 84:16 by all three rat liver microsomal preparations. The 9,10-dihydrodiol metabolite and its NaBH4 reduction products [a pair of diastereomeric 9,10-dihydroxy-9, 10-dihydro-2-OH 3MC (2-OH-3MC 9,10-dihydrodiols)] were characterized by UV-visible absorption, mass, and circular dichroic spectral, and chiral stationary phase HPLC analyses. Identification of 9,10-dihydroxy-9,10-dihydro-3MC-2-one (3MC-2-one 9,10 dihydrodiol) as the predominant metabolite of the potent carcinogen 3MC-2-one suggests that 3MC-2-one may be metabolically activated to a bay region 9,10-diol 7,8-epoxide, similar to the previously established metabolic activation pathways of 3MC and 1-hydroxy-3-methylcholanthrene (1-OH-3MC). PMID- 2323009 TI - Reduction of glutathione content by 12-O-tetradecanoylphorbol-13-acetate in confluent, but not in sparse cultures of human diploid fibroblasts. AB - Treatment of confluent cultures of human diploid fibroblasts with 12-O tetradecanoylphorbol-13-acetate (TPA) (10(-7) M) resulted in a 70% reduction of the glutathione (GSH) content, compared with untreated controls. The effect, which was dose-dependent, was observed 8 h after the beginning of the treatment could be followed for up to 72 h. On the other hand, GSH reduction was specific for confluent cultures, as the level of glutathione remained unchanged by TPA treatment of sparse cultures. The addition of immobilized plasma membrane proteins to sparsely seeded cells has been shown previously to induce cellular reactions which are characteristic for confluent cultures. It was shown that TPA treatment of sparse cultures grown in the presence of immobilized plasma membrane proteins also resulted in a 70% reduction of glutathione content. These data agree with the postulated involvement of redox reactions in tumor promotion, and point to a central role of cell-cell contacts in the regulation of biochemical events which are critical in tumorigenesis. PMID- 2323010 TI - The fluorescence emission properties of dGuo-C8-AAF, dGuo-C8-AF and the imidazole ring-opened products of dGuo-C8-AF indicate a different dynamic structure for the various compounds. AB - The reactive metabolites of the carcinogenic N-acetyl-2-aminofluorene (AAF) form adducts with the guanine base of DNA. The fluorescence emission characteristics of N-(deoxy-guanosin-8-yl)-N-acetyl-2-aminofluorene (dGuo-C8-AAF), N (deoxyguanosin-8-yl)-2-aminofluorene (dGuo-C8-AF) and the two N7 = C8 imidazole ring-opened products of dGuo-C8-AF (ro-dGuo-C8-AF I + II) were investigated and related to their conformational properties. The dGuo-C8-AF adduct (phi F congruent to 4-5 X 10(-4) shows a broad and structureless emission band, which is attributed to the formation of an excited-state complex. In contrast, the emission spectra of dGuo-C8-AAF (phi F congruent to 1.10(-4] and both ro-dGuo-C8 AF compounds [phi F(ro-dGuo-C8-AF I) congruent to 4.10(-3); phi F(ro-dGuo-C8-AF II) congruent to 4.10(-4)] are narrow. This indicates that dGuo-C8-AAF and ro dGuo-C8-AF I + II do not decay into an exciplex as occurs in dGuo-C8-AF. The spectroscopic features are discussed in terms of the differences in the dynamic structure of the various compounds. PMID- 2323011 TI - Thirteenth Annual Conference on Shock. Durango, Colorado, June 8-June 11, 1990. Abstracts. PMID- 2323012 TI - Rational, cost-effective workup for thyroid nodules. PMID- 2323013 TI - Novel uses for cyclosporine A. PMID- 2323014 TI - Keys to effective management of chronic cancer pain. PMID- 2323015 TI - PTCA in evolution: why is it so popular? AB - The last 10 years have seen a dramatic increase in the number of percutaneous transluminal coronary angioplasty (PTCA) procedures performed in the United States. The increase can be attributed to experience and improved technology, which have made PTCA a viable and effective procedure for an increasing number of coronary disease patients--including those with traditional high-risk factors such as advanced age and multivessel disease. Data from 9,000 PTCA procedures performed at the Mid-America Heart Institute of St. Luke's Hospital in Kansas City, Missouri, show high success rates with few complications and low mortality. PMID- 2323016 TI - The acute abdomen in the geriatric patient. AB - Evaluating an elderly patient with an acute abdomen is a challenging clinical problem. THe diagnosis is more difficult to secure in this age group, because it is difficult to obtain an accurate history, and physical findings are more subtle. The major factors that increase mortality include associated medical diseases, emergent operations, and delay in recognition and treatment of the problem. Patients with widespread malignancy and generalized peritonitis fare poorly, but operative mortality in the geriatric group has improved significantly because of more prompt diagnosis, aggressive resuscitation, precise monitoring, and expedient but definitive procedures. As the proportion of elderly patients in the population continues to rise, it becomes increasingly important to evaluate and manage this problem expediently. PMID- 2323017 TI - The role of sigmoidoscopy for asymptomatic patients. Results of three annual screening sigmoidoscopies, polypectomy, and subsequent surveillance colonoscopy in a primary-care setting. AB - A total of 329 asymptomatic patients (aged 50 or older) underwent flexible sigmoidoscopy to screen for colonic neoplasia. Of these, 258 underwent a second examination after 1 year and 143 underwent a third examination after another year. Of 60 patients in whom polyps were found on one of the three examinations, 58 underwent colonoscopy and polypectomy; 77 adenomatous polyps were present in 39 of these patients. The incidence of adenomatous polyps was 7.9% for the first examination, 3.9% for the second, and 2.1% for the third. Of patients with an index polyp found by sigmoidoscopy, 57.5% had synchronous polyps discovered by colonoscopy. Thirty-six of 77 polyps in 24 patients showed dysplasia; 9 were less than 0.5 cm, 14 were 0.5 cm to 0.9 cm, and 13 were 1 cm or larger. Forty-four surveillance colonoscopies (done after initial colonoscopy and polypectomy) have been performed in 28 patients. Eighteen examinations resulted in finding 30 adenomatous polyps, of which 10 showed dysplasia. This study 1) is the first report of flexible sigmoidoscopy data to support the American Cancer Society recommendation of two serial screening sigmoidoscopies a year apart, 2) reinforces the concept that an index polyp indicates a need for a complete colonoscopy, 3) reinforces the need for ongoing surveillance by colonoscopy after detection of adenomas, and 4) adds to reports of dysplasia in diminutive polyps. PMID- 2323018 TI - Congenital heart diseases associated with coronary artery anomalies. AB - Coronary artery anomalies are commonly associated with congenital heart disease. It is important to recognize these anomalies to avoid errors in diagnosis, decrease technical difficulties in angiography, and prevent inadvertent injury in surgery. We found that of 66,884 patients who underwent coronary arteriography between 1972 and 1982 at the Cleveland Clinic Foundation, 1,000 had coronary anomalies. Of these, 101 had associated congenital anomalies: 29 had mitral valve prolapse, 18 had bicuspid aortic valves, 16 had tetralogy of Fallot, 11 had corrected transposition, 10 had a univentricular heart, 6 had coarctation of the aorta, 3 had ventricular septal defects, and 8 had miscellaneous congenital heart defects. The most common coronary anomaly was ectopic origin of a coronary artery: 30 from the sinus of Valsalva, 12 from the ascending aorta, 11 from the pulmonary artery. Nineteen patients had no left main trunk. Thirteen patients had coronary artery fistulas and 21 had miscellaneous coronary anomalies. PMID- 2323019 TI - Estrogen supplements in menopause. AB - The number of women aged 65 and older is expected to double by the year 2000, increasing the need for effective management of symptoms related to menopause. Contemporary management of menopause addresses the continuum of events associated with the effects of estrogen deprivation on quality and duration of life, including neuroendocrine changes, urogenital atrophy, sexual dysfunction, skin and hair changes, osteoporosis, and cardiovascular disease. The risks and benefits of management strategies, including hormone replacement therapy, must be weighted carefully by both physician and patient. The use of estrogens and progestins, alterative compounds, dosages, routes of administration, and their advantages and disadvantages must be analyzed. PMID- 2323020 TI - Conservative operations for breast cancer: current issues and controversies. PMID- 2323021 TI - Congenital heart diseases and coronary artery anomalies: a comparison of experiences. PMID- 2323022 TI - Disseminated cutaneous fungal infection and AIDS. AB - We report a case of recalcitrant generalized cutaneous polydermatophyte and Candida infection in an AIDS patient who responded very poorly to topical, oral, and intravenous therapy. The patient died of respiratory arrest secondary to pneumonia 14 months after a cutaneous fungal infection developed and 12 months after AIDS was diagnosed. Extensive cutaneous fungal infections refractory to treatment may be a presenting sign of HIV infection. PMID- 2323023 TI - Urticaria, nephritis, and pseudotumor cerebri. AB - The spectrum of chronic urticarial disease ranges from chronic urticarial skin lesions alone to well-characterized systemic lupus erythematosus with urticarial vasculitis as the major skin manifestation. Within this spectrum is the syndrome of urticarial vasculitis associated with systemic disease manifestations. There have been six previously recorded cases of urticarial vasculitis associated with pseudotumor cerebri. At least two of these have included membranoproliferative glomerulonephritis. The authors report a case of chronic urticarial disease associated with pseudotumor cerebri and membranoproliferative glomerulonephritis, but without demonstrable vasculitis. It is possible that this represents a distinct entity within the spectrum of chronic urticarial disease and cca be easily screened for in clinical practice. PMID- 2323024 TI - Cell attachment and neurite stability in NG108-15 cells: effects of 5'-deoxy, 5' methyl thioadenosine (MTA) compared with laminin, kinase inhibitor H-7, and Mn2+ ions. AB - Methylation inhibitors such as 5'-deoxy, 5'-methyl thioadenosine (MTA) have been shown to exert an intriguing spectrum of effects upon neural cells: inhibiting responses to nerve growth factor in PC12 cells; stimulating outgrowth of rapid onset neurites in NG108-15 cells; inhibiting the resorption and remodelling of these rapid-onset neurites; and inducing fibroblasts to extend long, multipolar, branched processes. To learn whether the apparently diverse effects of these agents might reflect some common underlying cellular sites of action, we examined simpler, short-term effects of MTA upon cell attachment and stability of rapid onset neurites in NG108-15 cells, and compared the effects with those produced by the kinase inhibitor H-7, substratum-bound laminin, or Mn2+ ions. MTA was shown to selectively enhance the response of cells and their neurites in attaching to their substrata, without inducing other 'adhesive' responses such as cell spreading or motility. The data suggest that MTA activates or increases the effectiveness of 'attachment receptors', and that this at least partially explains its neurite-promoting effects. While it is still premature to propose a common mechanism of action for MTA and related agents, all of their known effects thus appear to involve modulating responses generated at cell-surface receptors. A further clue is that kinase C activity appears to be critical, since cells pretreated with phorbol esters for 24 h (which down-regulated levels of kinase C) selectively failed to extend neurites in response to MTA, but responded normally to laminin and Mn2+ ions. PMID- 2323025 TI - Age- and diabetes-associated alterations in regional brain norepinephrine concentrations and adrenergic receptor populations in C57BL/KsJ mice. AB - The diabetes-associated changes in regional brain norepinephrine (NE) concentrations and related adrenergic receptor types were correlated with changes in blood glucose levels and body weight (obesity) in 4-16-week-old C57BL/KsJ (db/db) mice relative to corresponding age-matched control (+/?) parameters. Regional brain (i.e. frontal cortex, septal area, amygdala, hypothalamus and medulla) NE levels were determined by high performance liquid chromatography and compared to the associated changes in tissue alpha-1,2 and beta-adrenergic membrane receptor populations. All db/db mice exhibited overt hyperglycemia and obesity relative to controls between 4 and 16 weeks of age. Regional brain NE levels in diabetics were chronically elevated as compared to those of age-matched controls. All of the alpha 1 and alpha 2 adrenergic receptor populations were elevated in the regional brain samples of diabetics relative to controls. In contrast, beta-adrenergic receptor populations were depressed in diabetics as compared with age-matched controls. These data demonstrate that a marked modification in regional brain adrenergic parameters occurs in association with the overt expression of the diabetes mutation in this species. The observed changes in adrenergic influences in specific CNS loci may be causally related to the recognized diabetes-associated alterations in regional brain structure, function and metabolism in C57BL/KsJ (db/db) mice. PMID- 2323026 TI - Development of the abducens nuclei in the Xenopus laevis. AB - The development of the main (nVI) and the accessory abducens (nVIa) nuclei was studied with the horseradish peroxidase and cobaltic-lysine labeling techniques in Xenopus laevis tadpoles. In earliest labeling was obtained at stage 39, and neuroblasts of both nuclei formed two separate groups according to their definitive positions in relation to other rhombencephalic structures in this young age of development. Conspicuous morphological differences were observed between the two nuclei: the accessory abducens neuroblasts were twice as big as the abducens neuroblasts and the characteristic nVIa 'knee' was present from this time of the first successful labeling. The two different dendritic arborization patterns, which clearly distinguished the abducens neurons from the accessory abducens neurons, gradually developed in tadpoles. It is suggested that the form and position of abducens and accessory abducens neurons are determined at a prefunctional stage, probably before the beginning of axonal outgrowth, and neurobiotaxis may not play the role attributed previously in the differentiation of these two nuclei. PMID- 2323027 TI - Postnatal development of corticotropin releasing factor-like immunoreactive amacrine cells in the rat retina. AB - The postnatal development of the corticotropin releasing factor-like immunoreactive (CRF-LI) amacrine cells was investigated in the Long-Evans rat retina. The pattern of development of CRF-LI cells was studied by immunohistochemistry, their cell number and density throughout the first two weeks of postnatal development were analyzed, and correlative measures of CRF-LI content were obtained using radioimmunoassay (RIA). The overall pattern of CRF-LI development, as revealed by either method, is characterized initially by faint staining and low content, respectively, which began to increase in staining intensity and content until a peak was reached around postnatal day (PD)-15, the time of eye opening. In determining cell number and density, emphasis was placed on the relationship between the development of CRF-LI neurons in the inner nuclear layer (INL) and that in the ganglion cell layer (GCL). Such quantitative analyses revealed a series of dynamic shifts in the distribution of CRF-LI cell density in both a horizontal orientation and a vertical orientation prior to PD 15. Horizontally, the shift involved a center-to-periphery density gradient which disappeared progressively as the retina matured. Vertically, a reciprocal change in total cell number occurred; the number of CRF-LI cells in the INL decreased while that in the GCL increased. These changes stabilized by PD-15 and, by PD-19, the CRF-LI cells appeared morphologically mature. PMID- 2323028 TI - Post-translational modification of alpha-tubulin by acetylation and detyrosination in NB2a/d1 neuroblastoma cells. AB - Western blot analyses of total assembled microtubule fractions from NB2a/d1 neuroblastoma cells demonstrated that these cells are capable of post translationally modifying alpha-tubulin by acetylation and detyrosination. Immunocytochemical analyses of NB2a/d1 cells differentiated with dbcAMP which had been processed under microtubule-stabilizing conditions demonstrated that all forms of alpha-tubulin were present throughout perikarya and neurites. By contrast, extraction of cells with Triton X-100 revealed a regional concentration of acetylated and detyrosinated alpha-tubulin subunits within axonal neurites, detectable in some cells after 3 days of differentiation and in nearly all cells after 7 days. Resistance of neurites to retraction following colchicine-treatment developed at a similar rate; furthermore, colchicine-resistant neurites contained intense acetylated alpha-tubulin immunoreactivity. We conclude that NB2a/d1 cells are capable of acetylating and detyrosinating alpha-tubulin subunits and that selective post-translational modification of alpha-tubulin subunits may be related to neuritic maturation. PMID- 2323030 TI - Ultrastructure of individual neurons isolated from avian retina: occurrence of microtubule loops in dendrites. AB - To investigate the cytoskeletal organization of neurons differentiating in vivo, we developed a procedure for isolating single arborized chick retina neurons, using papain and EGTA, and examining their structure in whole mounts. Ultrastructure of neurite tips and many regions along the neurite could be examined in detail in these preparations. Twenty to 25 nm linear elements which made tight 180 degree turns and returned to the original neurite were commonly observed in both detergent-extracted and intact whole mounts. The looped structures were identified as microtubules using antibodies to chick brain tubulin. Microtubule loops were prevalent in neurites at all ages examined, embryonic day 7-10 days post-hatch (E7-P10), but loops increased in frequency from being present in 24% of E7 neurites to 64% of E16 neurites. Often several neurites from the same cell contained microtubule loops, implying that at least some neurites with microtubule loops were dendrites. PMID- 2323029 TI - Biochemical differentiation of nascent neurite junctions: unilateral localization of adheron components. AB - Previous work showed that adhesive contacts made by growth cone filopodia involve extracellular filaments that can be labeled with an antiserum to adherons (adhesion-promoting complexes in conditioned medium). Here, adheron antigens were found to be differentially expressed by particular cell types and synaptic layers during chick retina development, and this differential expression at the cellular level was retained in culture. When applied to living cells, adheron antibodies characteristically patched at filopodial junctions. Monospecific antibodies to purpurin and a heparan sulphate proteoglycan (HSPG), two components of adherons, labeled a subpopulation of junctions. Most interestingly, anti-purpurin and anti HSPG bound only to one end of adhesive filaments. Such localization to discrete microdomains provides support for a heterotypic adhesive mechanism in junction formation. PMID- 2323031 TI - The developmental emergence of a map of auditory space in the superior colliculus of the guinea pig. AB - We describe the developmental emergence of a topographically ordered map of auditory space in the deep layers of the guinea pig superior colliculus. The central auditory system of this precocial mammal is functional in utero. A map of auditory space in the superior colliculus is not, however, electrophysiologically demonstrable until 32 days after birth (DAB). The map develops in 4 postnatal phases. In very young animals (1-15 DAB) vigorous responses to auditory stimuli were recordable from collicular sites. Apart from a preference for stimuli orginating in the contralateral hemifield of auditory space, the responses in these young animals, however, showed little evidence of directional tuning. In animals aged between 16 and 30 DAB, an increasing proportion of responses displayed directional tuning but such responses were not arranged so as to constitute a topographic map. A relatively short third developmental phase (31-32 DAB) involved the ordering of individually tuned responses so as to form a topographic map of the contralateral auditory hemifield. As the animals further mature the individual responses display a higher degree of spatial tuning reflecting an ongoing process of refinement. PMID- 2323032 TI - Amygdala kindling and associated changes of entorhinal responses in suckling rats. AB - Entorhinal field potential with amygdala stimulation in suckling (16-18 days old) and adult rats was recorded with a tungsten wire electrode (tip diameter 2-5 microns) to study the developmental changes in behavioral seizures and long-term potentiation (LTP) in the responses to amygdala kindling stimulations. Stimulating (twisted enamel-coated wires) and recording electrodes were implanted in anesthetized rats 2-3 days before kindling. The mean amplitude of the responses to test pulses (600 microA, 0.3 Hz) in the sucklings (0.58 mV) was smaller than in the adults (1.32 mV), and latency was about 3.3 ms longer. Kindling stimulations consisted of 0.5-ms monophasic rectangular pulses of 10 Hz with a 10-s train duration; the intensity was the afterdischarge (AD) threshold. Kindling stimulation in the sucklings usually increased the amplitude of the test responses evoked 10 min or 1 h after the kindling stimulation. The increased amplitude persisted for at least 24 h, showing LTP in the synaptic transmission. The LTP was especially prominent in the first kindling stimulation, and the LTP gradually increased with successive stimulations, with gradual progression of AD and the behavioral seizure stage as well. The mean number of kindling stimulations to cause generalized seizures in the suckling rats (10.5) was less than that for adults (12.5), and the continued evolution of LTP over the course of kindling was more or less easier in the sucklings than in the adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323033 TI - Modification of amygdaloid kindling by diazepam in juvenile rats. AB - The amygdaloid kindling phenomenon has been widely used to evaluate and screen potential anticonvulsant compounds in adult rats. In the current study, weanling rats (ages 23-25 days) were implanted chronically with amygdaloid electrodes. They were treated with dimethylsulfoxide (DMSO), 0.5 mg/kg diazepam or 1.0 mg/kg diazepam before twice daily kindling stimulations to determine the effect of diazepam on the acquisition of the kindled seizure. Additional juvenile rats implanted as weanlings and simulated twice daily without drug pretreatment until fully kindled were used to test for the acute anticonvulsant effects of diazepam (0.25-4.0 mg/kg). Diazepam was demonstrated to have anticonvulsant properties in juvenile rats by both prolonging the time to develop the fully kindled response during acquisition and by reducing the elicited seizure severity and the length of the afterdischarge in the fully kindled juvenile rats. Together, these data point to the extension of the anticonvulsant profile of diazepam to now include juvenile amygdaloid kindling in rats. They further point to the potential ability of screening proposed anticonvulsant drugs for their efficacy against amygdaloid kindling in immature rats. PMID- 2323034 TI - Developmental brain abnormalities accompanied with the retarded production of S 100 beta protein in genetic polydactyly mice. AB - The homozygotes of a mouse strain with genetic polydactyly (Polydactyly Nagoya, Pdn) exhibit various brain malformations including exencephaly in about 20%. In the present report, the brains of homozygotes (Pdn/Pdn) which were not exencephalic were examined morphologically and biochemically. Homozygous newborn brains showed hydrocephaly, some gyri on the cerebral hemisphere, absence of the corpus callosum, absence of the commissura anterior, absence of the fornix and commissura fornicis, protuberance of the cortical tissue from the brain surface, and abnormal architecture of the hippocampus. An irregular mass of olfactory nerve was observed on the cribriform plate, and the olfactory bulb was deficient. From these findings, we considered Pdn/Pdn as a kind of arhinencephalic mouse. Nervous tissue-related proteins, S-100 alpha, S-100 beta, creatine kinase B (CK B), neuron-specific gamma-enolase, guanosine triphosphate binding proteins (Go alpha, Gi2 alpha and G beta) were immunoassayed in the cerebrum of Pdn/Pdn embryos and newborns. Among the protein analysed, only S-100 beta of Pdn/Pdn showed a significantly lower level than that of +/+ cerebrum during the observation period. The newborn brains were examined immunohistochemically using S-100 alpha, S-100 beta, CK-B, Go alpha and NSE antibodies. We could find no differences in the staining patterns among the Pdn/Pdn, Pdn/+ and +/+ brains. PMID- 2323035 TI - Differentiation potential of a monoclonal antibody-defined neural progenitor cell population isolated from prenatal rat brain by fluorescence-activated cell sorting. AB - We have studied the differentiation potential in vitro of a subpopulation of neural progenitor cells from BDIX-rat brain. These cells transiently express a cell surface determinant (CSD) specified by monoclonal antibody (Mab) RB13-2 (Kindler-Rohrborn, A. et al., Differentiation 30 (1985) 53-60), and recently identified as a set of O-acetylated gangliosides (Reinhardt-Maelicke, S. et al., submitted) also recognized by Mab D1.1 (Levine, J.M. et al., J. Neurosci., 4 (1984) 826-831) and partly by Mab JONES (Schlosshauer, B. et al., J. Neurosci., 8 (1988) 580-592), respectively. As analyzed by immunofluorescence, Mab RB13-2 binding brain cells (prenatal days 11-22; postnatal days 7 and 89) were localized in different areas of the proliferative ventricular layer of the prenatal cerebrum and in the external granular layer of the early postnatal cerebellum. No Mab RB13-2 positive brain cells were found in adult brain. Following their isolation by fluorescence activated cell sorting on prenatal day 18, the differentiation potential of Mab RB13-2 binding brain cells was studied by double immunofluorescence analysis under different conditions of monolayer culture. In the presence of 10% fetal calf serum (FCS), these cells differentiated into glial fibrillary acidic protein (GFAP) positive flat astrocytes, whereas neurons (neurofilament-positive) and a smaller number of stellate astrocytes (GFAP positive) developed in a chemically defined medium containing 0.5% FCS. Neural progenitor cells binding Mab RB13-2 may thus either retain more than one option for differentiation into specific cell types, or the expression of the CSD specified by Mab RB13-2 may be common to more than one subset of neural progenitor cells (with or without predetermined unidirectional differentiation pathways) whose survival and/or proliferative behavior could be differentially affected by microenvironmental conditions. PMID- 2323036 TI - Differential recognition of a set of O-acetylated gangliosides by monoclonal antibodies RB13-2, D1.1, and JONES during rat brain development. AB - Monoclonal antibodies (Mab) RB13-2, JONES, and D1.1 all recognize gangliosides expressed on the surface of prenatal rat brain cells. As shown by high performance thin-layer chromatography (HPTLC) immunoblotting of enriched rat brain gangliosides from different stages of development, all these Mabs bind to O acetylated GD3 and (weakly) to an as yet unidentified double-band. Both Mab RB13 2 and Mab D1.1 recognize two additional minor gangliosides. Immunofluorescence analyses of frozen serial sections of prenatal rat brain show that, in addition to the cell subpopulations stained with all three antibodies, Mab RB13-2 and Mab D1.1 recognize further subpopulations of neural cells. These additional Mab JONES negative cells apparently express minor ganglioside(s) identified in the immunoblots. PMID- 2323037 TI - Histamine increases ornithine decarboxylase activity in primary cultures of cerebellar granule cells. AB - The effect of histamine on the activity of ornithine decarboxylase (ODC) of cerebellar granule neurons was studied using primary cultures grown both in serum containing medium and in chemically defined medium. In comparison with granule neurons grown in chemically defined medium, the activity of ODC was about twice as great in the neurons grown in serum-containing medium. Treatment of cultured cerebellar neurons with histamine caused a dose-dependent increase in ODC activity. The maximum elevation was observed at 500 nM of histamine, when the increase in ODC activity was about 50% and 120% over controls in granule cells grown in serum-containing medium and in chemically defined medium, respectively. Histamine had no significant effect on the activity of lactate dehydrogenase in these cultures. The present findings provided direct evidence for the involvement of histamine in the regulation of ODC-related non-mitotic growth of granule neurons in the cerebellum. PMID- 2323038 TI - Neuron-glia interactions: effect of serotonin on the astroglial expression of GFAP and of its encoding message. AB - The trophic effect of serotonin on the glial fibrillary acidic protein (GFAP) expression was investigated in rat brainstem astrocytes in primary culture. GFAP immunolabelling decreased and gliofilaments appeared localized in the cytoplasm periphery. GFAP protein level decreased in parallel with a decrease in its encoding message. Serotonin may act as an inhibitor of GFAP expression either on the transcription or on the stability of the GFAP-mRNA. PMID- 2323039 TI - Investigation of interference by nonsteroidal anti-inflammatory drugs in urine tests for abused drugs. AB - Anecdotal and uncontrolled studies have suggested that nonsteroidal anti inflammatory drugs produce false-positive results in immunoassay urine tests for some drugs of abuse. This study was performed in 60 volunteers who took ibuprofen as either a single 400-mg dose, or 200 mg three times a day, or 400 mg three times a day, and in 42 patients taking ibuprofen, naproxyn, or fenoprofen in therapeutic regimens for more than 30 days. Of the 510 urines collected from 102 individuals during these dosage regimens, two gave false-positive tests for cannabinoid by enzyme-mediated immunoassay (EMIA), one after 1200 mg of ibuprofen in three divided doses for one day and one in a patient taking naproxyn on a chronic basis; none was falsely positive for benzodiazepines. Two urines were false-positive for barbiturates by fluorescence polarization immunoassay (FPIA), one in a patient taking ibuprofen and one in a patient taking naproxyn. These data, collected prospectively, demonstrate the small likelihood of a false positive immunoassay test result for cannabinoids, benzodiazepines, or barbiturates after the acute or chronic ingestion of ibuprofen, or after the chronic ingestion of naproxyn or fenoprofen. PMID- 2323040 TI - Determination of carbamylated hemoglobin by high-performance liquid chromatography. AB - We have developed an HPLC method for measuring carbamylated hemoglobin (CarHb), based on the quantification of valine hydantoin formed from the released NH2 terminal carbamyl valine residue after acid hydrolysis of hemoglobin. In uremia, CarHb is produced by nonenzymatic post-translational modification of the terminal amino group of hemoglobin monomers by isocyanic acid, derived from the spontaneous dissociation of urea. We measured CarHb in 25 nonuremic control subjects, 24 nonuremic diabetic subjects, and 30 patients with stable chronic renal failure. There was no significant difference between the controls and diabetic patients, their mean (SD) CarHb values being 41 (11.5) and 38 (10.8) micrograms of carbamyl valine per gram of hemoglobin (microgram CV/gHb), respectively. Mean (SD) CarHb values in the uremic patients were much greater, 164 (87.7) microgram CV/gHb. There was significant correlation between the concentrations of CarHb and plasma urea in the uremic subjects. Thus CarHb provides a urea-derived index of chronic uremia. PMID- 2323041 TI - In vitro and in vivo effects of increased concentrations of free fatty acids on free thyroxin measurements as determined by five assays. AB - To compare in vitro and in vivo effects of increased concentrations of free fatty acids (FFA) on free thyroxin (FT4) values, we measured FT4 in three pooled sera supplemented with oleate and in serum from 18 euthyroid patients before and after an infusion of fat emulsion (Intralipid). We used five FT4 RIA kits: two two-step methods [Gammacoat, Baxter (GC); Ria-gnost, Behring (RG)], two analog RIAs [Amerlex-M, Amersham (AM); Coat-Ria, BioMerieux (CR)], and one kit with labeled antibodies [Amerlex-MAB*, Amersham (AA)]. In vitro, at the maximum oleate addition of 5 mmol/L, FT4 increased when measured by the GC and RG kits, decreased by the AM kit, and showed no significant change by the CR and AA kits. In vivo, post-Intralipid, FFA concentrations rose significantly and the FT4 changes agreed with the results of the in vitro experiments, except for the RG kit, for which FT4 increased in only nine patients. We conclude that in vitro oleate addition is useful to predict the in vivo effect of increased FFA on FT4 values; moreover, in serum from euthyroid subjects with high concentrations of FFA, FT4 analyzed with the CR or AA kits should better agree with normal results for thyrotropin than FT4 values measured with the other kits. PMID- 2323042 TI - Blood cholesterol concentration: fingerstick plasma vs venous serum sampling. AB - To assess whether venous and fingerstick blood samples yield similar cholesterol concentrations, we obtained both types of samples simultaneously in 108 volunteers participating in a cholesterol screening program. All samples were analyzed by the same enzymatic method in a standardized laboratory, and pairs of simultaneous samples were measured in the same laboratory run. Cholesterol concentrations in fingerstick-derived plasma were consistently higher than in the venous serum (P less than 0.0001), by a positive bias averaging 3.6%. Cholesterol values in fingerstick plasma also were higher than cholesterol results for venous serum placed in a capillary collection tube (average bias +2.4%). The positive bias of fingerstick plasma vs venous serum results appears to be at least partly due to specimen handling, although a true physiological difference between venous and fingerstick cholesterol concentrations is probably also involved. If a positive bias of this magnitude from fingerstick blood sampling is left unadjusted, substantial numbers of people will be labeled "at risk" and referred to physicians when their true values were actually within the acceptable range. PMID- 2323043 TI - S-100ao protein in serum during acute myocardial infarction. AB - Concentrations in serum of S100ao protein (alpha alpha form of S-100 protein, which is present at high concentrations in heart muscle) were successively measured by enzyme immunoassay in 21 patients with acute myocardial infarction (AMI) and six with angina pectoris (ANP). Results were compared with measurements of creatine kinase isoenzyme MB (CK-MB) concentrations in the same specimens. Mean S100ao concentrations in sera from 100 healthy adults were 0.12 (SD 0.08) microgram/L. In patients with AMI, S100ao concentrations were 4.74 +/- 5.27 micrograms/L at admission, peaked 8 h after admission (23.5 +/- 27.7 micrograms/L), then decreased gradually. Among nine AMI patients who were admitted within an hour after their attack, eight showed abnormally high concentrations of S100ao in serum (greater than 0.5 microgram/L), whereas only four showed abnormally high CK-MB concentrations (greater than 5 micrograms/L) in sera at the time of admission. Serum S100ao concentrations remained within the normal range in all six patients with ANP; however, serum CK-MB concentrations were increased in two of them. Therefore, serum S100ao is useful not only for detection of AMI but also for differentiating AMI from ANP. PMID- 2323044 TI - Urinary hydroxyproline in infants with and without fractures/rickets. AB - Molar ratios of peptide-bound and free hydroxyproline:creatinine (OHPr:Cr) in urine were measured at 3, 6, 9, and 12 months of age in two groups of very-low birthweight (VLBW less than or equal to 1500 g) infants. Group A (15 infants) had radiographically confirmed fractures and (or) rickets (F/R); Group B (17 infants) did not. The urinary peptide-bound OHPr:Cr ratio varied widely within groups and was greatest at three months in both groups: A = 0.81 +/- 0.45 and B = 0.55 +/- 0.32 (mean +/- SD). The ratio decreased with increasing postnatal age for each group but was not statistically different between groups throughout the study. The urinary free OHPr:Cr ratio also was greatest at age three months (A = 0.32 +/ 0.15 and B = 0.53 +/- 0.46), rapidly decreasing afterwards, and was not statistically different between groups throughout the study. We conclude that, in VLBW infants, bone turnover as indicated by the urinary peptide-bound OHPr:Cr ratio is highest during early infancy; however, the wide range of values for this ratio suggests that its use alone is not sufficient for detection of F/R in VLBW infants. The rapid decrease in free OHPr:Cr ratio is presumably related to the maturation of renal tubular function. PMID- 2323045 TI - Improved method of analysis for aluminum in brain tissue. AB - To improve the accuracy and precision of the assay of aluminum in brain tissue, we modified for application to brain samples from rats and humans the wet digestion method of Trapp et al. (Biol Psychiatry 1978; 13:709-18), established the contribution of contamination, and examined the effect of precipitation of nonoxidizable fatty residues on the analysis. Specifications of the modified assay are a detection limit of 5 ng of aluminum per gram wet weight of brain tissue, a within-day CV of 4.8% (24.3 microgram/L; n = 10), and a day-to-day CV of 5.5% (27.8 micrograms/L; n = 5). Contamination, a systematic error in the analysis of aluminum, was established to be 13 ng (SD = 7.9 ng; n = 8) per tube. The presence of indestructible fatty residues did not affect the accuracy of the method. Application of the method to brain hemispheres of nonexposed rats revealed an aluminum content of 0.041 mg/kg wet weight of tissue (SD = 0.032 mg/kg; n = 8). The aluminum content in human cortex samples, consisting of gray and white matter, ranged from 0.14 to 0.22 mg/kg. Modification of the wet digestion method resulted in a reliable, simple sample pretreatment before analysis for aluminum in brain tissue. The extent of the aluminum contamination must be controlled by including appropriate blanks. PMID- 2323046 TI - Dichlorobenzoquinone chloroimine colorimetry of uric acid in urine. AB - In this nonenzymatic colorimetric method, dichlorobenzoquinone chloroimine is used as a color reagent to measure uric acid in urine. This method is less subject to the interferences that make enzymatic methods unreliable and is inexpensive, simple, and fast. PMID- 2323047 TI - Use of free and transthyretin-bound retinol-binding protein in serum as tests of vitamin A status in humans: effect of high creatinine concentrations in serum. AB - We measured immunologically active (apo + holo) retinol-binding protein (RBP), vitamin A-carrying (holo) free RBP, and transthyretin-bound (TTR) holo-RBP in serum from 34 retrospective cases of fluctuating acute renal failure. All subjects had high serum creatinine concentrations caused by renal failure. Apo + holo, holo-TTR-RBP, and (especially) holo-free RBP all correlated poorly but significantly with serum creatinine concentration. Therefore, the use of any form of RBP to measure vitamin A status may be of limited value in subjects with high creatinine concentrations in serum. However, molecular-exclusion HPLC may be able to distinguish increases in RBP concentration associated with renal failure from those caused by altered vitamin A status, because renal failure causes abnormalities in the number and retention times of chromatographic peaks as well as their areas. PMID- 2323048 TI - Retention of antimony in skin biopsies of leishmaniasis patients after treatment with N-methylglucamine antimoniate. AB - Leishmaniasis patients were treated with N-methylglucamine antimoniate by intravenous injections of 10 or 20 mg of Sb per kilogram of body weight per day for 10 or 20 days. Digests of skin biopsies taken from the site of lesion before and after treatment were analyzed for antimony by instrumental neutron activation (INAA). The detection limit of the assay was 20 ng, and no Sb could be measured in digests of samples (less than 2.45 mg) taken before treatment. Biopsies taken after injections of Sb showed concentrations in the range of 8.32 to 70.68 ng/g skin. We discuss the usefulness of INAA in the study of Sb in small samples of tissues. PMID- 2323049 TI - Measurement of pepsinogen group I in endoscopic gastroduodenal biopsies. AB - A technique for determining pepsinogen group I (PGI) concentrations in endoscopic gastroduodenal biopsies is described and validated. This method has a good precision (intra-assay CVs 4.1% to 8.4%; between-assay CVs 4.6% to 9.3%), and analytical recovery is satisfactory (94% to 102%). Results were uninfluenced by the storage interval of the samples. At PGI-producing sites (i.e., fundus, corpus) peptic activity was greater than in the antrum and duodenum. PGI concentrations in serum and in gastroduodenal biopsies were not correlated. This simple, reliable method can quantify better than other assays peptic activity in humans, without being influenced by gastric secretory volumes. It will also facilitate prospective studies on the effect of various secretagogues in vivo and evaluations of the influence of anti-ulcer drugs on peptic secretion. PMID- 2323050 TI - Grand rounds at Sahlgren's Hospital: chronic abdominal pain in a middle-aged woman--psychosomatic disorder or identifiable somatic disease? PMID- 2323051 TI - Cystic fibrosis deletion mutation detected by PCR-mediated site-directed mutagenesis. PMID- 2323052 TI - Fibrinogen determination by five methods in patients receiving streptokinase therapy. PMID- 2323053 TI - Graphic representation of reference intervals. PMID- 2323054 TI - Automated analysis for urinary protein by pyrogallol red-molybdate method. PMID- 2323055 TI - Measurement of zinc protoporphyrin with the ProtoFluor-Z System. PMID- 2323056 TI - Digoxin-like immunoreactivity detected in cerebrospinal fluid of humans with fever. PMID- 2323057 TI - Concentrations of neopterin and biopterin in serum from patients with rheumatoid arthritis or systemic lupus erythematosus and in synovial fluid from patients with rheumatoid or osteoarthritis. PMID- 2323058 TI - 7S monoclonal IgM in quantitative systems. PMID- 2323059 TI - Lactate dehydrogenase isoenzyme 1 activity in sera of patients with ovarian cancer. PMID- 2323060 TI - Sialyllacto-N-fucopentaose II (sialylated Le(a)) coupled to humanserum albumin used as standard in immunoassays of tumour associated antigens CA 19-9 and CA-50 in serum. AB - Penta and hexasaccharides from human milk, containing sialic acid and/or fucose residues were conjugated to human serum albumin and used as antigens in three different methods for CA 19-9, two methods for CA-50 and one method for CA-195. In accordance with reported results, the 19-9, CC 3C 195 and C-50 monoclonal antibodies were found to react with the sialyllacto-N-fucopentaose II conjugate, although to a different extent. A negligible reaction was observed with the isomeric conjugate, sialyllacto-N-fucopentaose III, and no reaction was seen with the sialyllacto-N-tetraose conjugate. The use of defined oligosaccharide conjugates for the standardization of assays of tumour markers in serum is discussed. PMID- 2323061 TI - Characterization of a monoclonal antibody specific for prostatic secretory protein of 94 amino acids (PSP94) and development of a two-site binding enzyme immunoassay for PSP94. AB - Purified prostatic secretory protein of 94 amino acids (PSP94) was used to generate polyclonal rabbit anti-PSP94 IgG and a murine monoclonal antibody 6B6 (mAB6B6). Both antibodies were highly specific for PSP94 by immunoblotting. Immunohistochemical studies demonstrated the specificity of mAB6B6 for human prostatic epithelial tissue. A two-site binding enzyme immunoassay for the detection of PSP94 was developed using a combination of the antibodies. The sandwich-ELISA yielded satisfactory results when mAB6B6 complexed to peroxidase conjugated goat anti-mouse-IgG (Fc) was incubated simultaneously with the sample. The assay has a dynamic range of 2-30 micrograms/l. This immunoassay was employed to measure PSP94 in male human sera (8 +/- 4 micrograms/l), female human sera (5.7 +/- 3.4 micrograms/l), follicular fluid (3.9 +/- 2.9 micrograms/l) and human seminal plasma (1.02 +/- 0.8 g/l). PMID- 2323062 TI - Demonstration of a combined deficiency of xanthine oxidase and aldehyde oxidase in xanthinuric patients not forming oxipurinol. AB - Genetic heterogeneity has been suggested in xanthinuria from the hitherto unexplained ability of some patients with this hereditary disorder to convert allopurinol to its active metabolite oxipurinol--an activity generally attributed to xanthine oxidase. This study provides evidence that the enzyme aldehyde oxidase is also deficient in xanthinuric patients not converting allopurinol to oxipurinol, whereas a xanthinuric patient with normal formation of oxipurinol had normal aldehyde oxidase activity. It is concluded that the enzyme aldehyde oxidase is the principal enzyme responsible for the formation of oxipurinol in man. PMID- 2323063 TI - Microheterogeneity of alpha 1-acid glycoprotein: variation during the menstrual cycle in healthy women, and profile in women receiving estrogen-progestogen treatment. AB - The concentration of alpha 1-acid glycoprotein (AGP) was measured in sera from 23 women, 14 pregnant women, 10 women receiving estrogen-progestogen treatment and 12 men. All sera were further subjected to crossed affino-immunoelectrophoresis with addition of conA in the first dimension and alpha-methylglucopyranoside in the second dimension. The distribution of AGP into three microheterogeneity forms, which were the result of this analysis, was estimated by measuring the area under the precipitation curve. The microheterogeneity patterns of AGP in the five groups were analysed from each other. An augmentation of the non reactive form is seen in women in the first part of the cycle and in women receiving estrogen-progestogen treatment compared with the three others groups. The pattern obtained in this latter group is similar to that observed in pregnant women (34 weeks) by several authors. PMID- 2323064 TI - Comparative evaluation of the diagnosis of acute pancreatitis based on serum and urine enzyme assays. AB - We compared the diagnostic sensitivities of serum amylase, lipase (assayed enzymatically and immunologically), trypsinogen and elastase-1, the 2-h-timed urine amylase excretion and the ratio of amylase and creatinine clearances in the recognition of acute pancreatitis. Serial serum and urine findings from 39 patients with acute pancreatitis, and from 42 patients with non-pancreatic causes of abdominal pain (controls), as well as findings from 24 healthy subjects (normals) were studied. Decision thresholds were established for each parameter using either the control or the normal population, and the resulting diagnostic sensitivities determined. On hospital admission, all serum assays were equally sensitive, but on subsequent days lipase, trypsinogen and elastase-1 assays all significantly surpassed the sensitivity of the serum amylase assay. On the second and subsequent hospitalization days, determination of timed urine amylase excretion offered no advantage over the serum amylase, and the ratio of amylase and creatinine clearances lacked discrimination altogether. PMID- 2323066 TI - Variations in serum alpha-L-fucosidase activity during childhood and pregnancy. AB - Variations in serum alpha-L-fucosidase activity (AFU) have been studied during childhood and pregnancy. 994 children, ages 1 day to 15 yr, were examined; no sex linked difference was found, but significant variations according to age were demonstrated. AFU activity rose during the first 10-15 days after birth, remained high during the second month then decreased till the end of the first year, thereafter no significant changes were observed. In pregnancy, AFU activity rose and dropped quickly after delivery; neither hypertension nor fetal distress led to AFU activity changes during pregnancy. Thus, in addition to the great variability of AFU linked to the genetic polymorphism, the physiological factors such as age or pregnancy have to be taken into account to establish the significance of AFU variations in pathological situations. PMID- 2323065 TI - Anti-skeletal muscle antibodies in the sera from myasthenic patients with thymoma: identification of anti-myosin, actomyosin, actin, and alpha-actinin antibodies by a solid-phase radioimmunoassay and a western blotting analysis. AB - We recently reported a strong association between the occurrence of anti-skeletal muscle (SM) antibodies and the presence of thymoma in patients with myasthenia gravis (MG). To further examine the immunoreactivity of MG sera against human muscle antigens, we developed a solid-phase radioimmunoassay (RIA) using purified muscle antigens and a Western blotting analysis in MG sera with high titers of anti-SM antibodies. Our results showed that MG patients with thymoma (thymoma group) had markedly high titers of anti-myosin and anti-actomyosin antibodies than those without thymoma (non-thymoma group). Furthermore, a close correlation was found between titers of anti-SM, anti-myosin and anti-actomyosin antibodies. The antibody titers against actin, alpha-actinin and tropomyosin were all low and did not correlate with titers of anti-SM antibodies. But, significant levels of these three antibodies were found in the thymoma group. By a Western blotting analysis, immunoreactivity of sera from the thymoma group appeared to be predominantly directed against myosin, actin and alpha-actinin. PMID- 2323067 TI - A routine method for the measurement of the sodium, potassium, magnesium and calcium content of human lymphocytes. AB - We describe a rapid, single-step procedure for the isolation of human lymphocytes from whole blood, suitable for a routine clinical laboratory. Lymphocyte content of sodium, potassium, magnesium and calcium were measured simultaneously in a group of controls and found to fall within expected ranges. Expression of results per mg protein produced less inter-individual variation than per unit cell. In order to examine another, physiologically different but normal population, women during pregnancy were also studied. The cation content of lymphocytes expressed per mg protein was significantly lower than for controls due to a 44% increase in protein content per cell. PMID- 2323068 TI - How should urinary cotinine concentrations be adjusted for urinary creatinine concentration? AB - The correlation between cotinine concentrations in a single specimen of urine and in serum collected on the same occasion from 279 male smokers was 0.83. This was significantly increased, to 0.91, by adjusting the urinary cotinine levels for urinary creatinine concentration to take account of variations in urinary dilution between people. The adjustment used was based on the observed regression relationship between urinary cotinine and urinary creatinine concentrations. Expressing urinary cotinine values as a ratio to urinary creatinine, which has been used as a method of adjustment by others, did not improve the correlation between serum and urinary cotinine levels. The method of adjusting urinary cotinine for urinary creatinine is, therefore, important. The principle of such adjustment should apply not only to cotinine but also to other urinary biochemical measurements. PMID- 2323069 TI - Isoelectric focusing versus quantitative measurements in the detection of intrathecal local synthesis of IgG. AB - Specimens from 1007 patients with suspected neurological disturbances had quantitative and qualitative measurements made of cerebrospinal fluid and serum to investigate the presence of locally synthesised IgG. Qualitative measurement was recorded as the presence or absence of oligoclonal banding, and the quantitative measurement was derived by the use of the IgG index, the log index and the Reiber, Schuller and Tourtellotte formulae. The patients were divided into two categories, on the basis of banding: those with local synthesis and those without. The sensitivity, specificity and efficiency for each of the quantitative measurements were then calculated. Receiver-operator curves were also constructed for each of the quantitative measurements. 282 samples showed local synthesis of IgG by isoelectric focusing, whereas the best quantitative assay (log index) could only detect 198. Therefore, we conclude that oligoclonal banding should be adopted as the standard laboratory measurement of local synthesis of IgG in the diagnosis of neurological disorders, and that the diagnostic use of quantitative measurements should be abandoned for routine purposes. Furthermore, we suggest that quantitative analysis, at its current level, is misleading and has little value in the understanding of neurological disorders, but may be of use in serially monitoring individual patients as part of their therapeutic trials. PMID- 2323070 TI - Non-M CK--a practical measure of creatine kinase isoenzymes in cancer patients. AB - The individual creatinine kinase (CK) isoenzymes CK-BB and CK-Macro II have previously been investigated as potential tumour markers. We believe there is a need for a system to measure those CK forms not usually present in serum. We have studied a CK-MB immunoinhibition kit which measures all residual CK activity following inactivation of M-subunit activity. In 162 patients with cancer we found no difference in grading (+ or -) between detailed isoenzyme studies and the simple non-M assay. In 33 samples with elevated non-M CK, detailed analysis showed BB alone (45%), Macro II alone (9%), or both (36%). Raised activities were mainly found in patients with small cell lung cancer (SCLC) (17/40; 43%) and GI Tumours (6/11; 55%). In patients with SCLC, elevated activities were associated with disseminated disease. Preliminary evidence indicates that Non-M CK may also be a simple means of monitoring initial treatment response. PMID- 2323071 TI - Measurement of L-carnitine and acylcarnitines in body fluids and tissues in children and in adults. AB - We have developed a reliable and validated radio-enzymatic method for the assay of L-carnitine and acylcarnitines, using a modification of existing methods. The sensitivity of the assay is 10 mumol/l using 10 microliters of plasma or urine. It is also suitable for measurements of carnitine in a 10 mg sample of liver or muscle obtained by percutaneous biopsy. The use of N-ethylmaleimide in the reaction mixture together with an excess of [1-14C]acetyl CoA ensures that the reaction proceeds to completion and a linear response is obtained. Using this method control ranges have been established for plasma and urine carnitine concentrations in healthy children and adults, and for the carnitine content of liver and muscle in adults. No significant difference was found between fasting and post-prandial plasma carnitine levels. An age-related increase was found in urinary total carnitine and acylcarnitine concentration throughout childhood. These data provide a reliable basis for studies of patients with abnormal carnitine and acylcarnitine metabolism, distribution and excretion. PMID- 2323072 TI - Early amniocentesis and amniotic fluid organic acid levels in the prenatal diagnosis of organic acidemias. AB - Organic acids were studied in amniotic fluids taken by early amniocentesis between 6 to 12 weeks in control pregnancies. The prenatal diagnosis of methylmalonic acidemia and propionic acidemia could be made by the measurement of methylmalonic and methylcitric acid respectively in the amniotic fluid taken simultaneously with chorionic villi at the 11th week of gestation. PMID- 2323073 TI - A carry-over study in three different instruments for the determination of serum glucose: the importance of Student's t test. PMID- 2323074 TI - Surgical treatment of obliterative otitis externa. AB - Seven patients with fibrous obliteration of the ear canal due to long-standing otitis externa were seen at St Mary's Hospital during the past 10 years. Two patients underwent bilateral surgery making a total of 9 ear cases. Two patients developed early restenosis within 6 months of permeatal excision of the fibrous core and skin grafting, and one patient had late stenosis 4 years following postaural excision, meatoplasty and skin grafting. Two of these patients opted for revision surgery and a total of 6 patients (8 ear cases) underwent postaural excision with Korner flap canalplasty, enlargement of the bony ear canal and skin grafting. The average hearing gain was 25 dB in the speech frequencies and only one restenosis was seen at 3 years. This was successfully revised. Radical excisional surgery with a wide bony canalplasty is recommended in this condition. PMID- 2323075 TI - Incidence, prognosis and recovery of Bell's palsy. A survey of about 1000 patients (1974-1983). AB - Over a 10-year period the diagnosis Bell's palsy was made in 1293 patients. The files of 1235 patients were studied; the relevant data were stored in a computer and analysed. Factors analysed included the source of referral of the patients as well as their age and sex, the time of onset of the paralysis, recurrence, side of the face, and pregnancy. The incidence of hypertension, diabetes and other diseases was evaluated. The fate of the nerve is determined to a large extent in the first week of the disease. The nerve excitability test is a reliable predictor of the final outcome. The system of classification of recovery we have used for many years is compared to the International Facial Nerve grading system. If denervation and poor recovery are to be prevented as far as possible, early examination and treatment of selected patients with prednisone is mandatory. An important factor in recovery is the age of the patient. PMID- 2323076 TI - Electrical stimulation of the round window: a selection procedure for single channel cochlear implantation. AB - Many suggestions have been made as to the most appropriate tests for the selection of patients for cochlear implantation. One of the most appropriate tests when selecting patients for a round window extracochlear device is stimulation of the round window itself by a temporary electrode of the same size. Fourteen patients have been tested, 7 of whom were judged to have a good response to electrical stimulation. Six patients have gone on to permanent implantation with a round window cochlear implant. PMID- 2323077 TI - Emergency laryngectomy. AB - Emergency laryngectomy is a laryngectomy carried out for malignant obstruction of the upper airway within 24 h of admission. This combines relief of the obstruction with definitive primary cancer surgery, and is thought to reduce the risk of post-laryngectomy stomal recurrence. During a 5-year period, 13 patients with upper airway obstruction from squamous cell carcinoma were treated in two departments by emergency laryngectomy. Total laryngectomy was carried out after the diagnosis of squamous cell carcinoma of the larynx (n = 11), or piriform fossa (n = 2), had been confirmed by laryngoscopy and frozen section biopsy. The actuarial 5-year survival was 47%, and no patient in this series developed stomal recurrence. The management of the airway obstruction, and the post-laryngectomy complications, did not differ from those encountered with more conventional treatment. Our experience with this approach suggests that emergency laryngectomy is a satisfactory method of managing airway obstruction due to squamous cell carcinoma of the larynx. PMID- 2323078 TI - The effects of menthol on reaction time and nasal sensation of airflow in subjects suffering from the common cold. AB - The effects of sucking a lozenge containing 11 mg L-menthol on reaction time and nasal sensation were investigated in a double blind trial on 60 subjects suffering from the common cold. Reaction time was determined by measuring the response time to a stimulus presented on a microcomputer screen and nasal sensation was scored on a visual analogue scale. Menthol ingestion compared to placebo caused a significant increase in nasal sensation of airflow which persisted for up to 30 min. The simple and choice reaction times measured before ingestion of the lozenge were similar to those found in healthy uninfected subjects and there was no change in reaction time after ingestion of menthol. PMID- 2323079 TI - A non-invasive electrophysiological technique for the measurement of 'tuning'. AB - The frequency selectivity of the auditory system is mainly determined by the activity of the cochlea. A method of measuring this selectivity has been developed by recording the extratympanic compound auditory nerve action potential using non-simultaneous masking. This provides a non-invasive 4-point tuning curve centered at 4 kHz which demonstrates the typical features expected from animal experiments. The non-interactive nature of the test makes it easy to perform and normative data has been collected on 10 subjects. PMID- 2323080 TI - Epistaxis: a study of the relationship with weather. AB - Epistaxis is the commonest ENT emergency requiring hospital admission. A seasonal variation in the admission rate has been documented. The role of weather in accounting for this variation is uncertain. A retrospective review of 686 adult hospital admissions for idiopathic spontaneous epistaxis over a 2-year period in the Greater Glasgow area was carried out. The most significant weather parameter which correlated with monthly admissions was mean monthly temperature (Pearson's correlation coefficient -0.81, P less than 0.01). Admissions increased by over 100% from the warmest to the coldest months. This is the first report of the high correlation between hospital admissions for epistaxis and mean monthly temperature. PMID- 2323081 TI - Functional assessment of the paediatric laryngeal airway. AB - After resolution of conditions necessitating tracheostomy in children, decannulation may be extremely difficult and associated with significant morbidity. Endoscopy and radiography can identify anatomical abnormalities preventing decannulation. Physiological abnormalities are, however, more difficult to assess. A system has been developed whereby functional upper airway resistance can be calculated in children with a tracheostomy. The instrument used was a modified Mercury Electronics rhinomanometer. A probe was placed through the tracheostome and another probe was situated in an occluding anaesthetic face mask. Upper airway resistance was derived from the differential pressure and flow changes recorded in anaesthetized children who were breathing spontaneously. Studies in 26 children have revealed low airway resistance in all those successfully decannulated. Further studies will hopefully allow identification in advance of children who will have decannulation difficulties. PMID- 2323082 TI - Do patients with otitis externa produce biochemically different cerumen? AB - As polyunsaturated fatty acids have better antibacterial properties than saturated fatty acids, the cerumen of seven patients with recurrent otitis externa and seven unaffected subjects was analysed to determine their ratio. There was no significant difference in either the overall ratio of unsaturated/saturated fatty acids or in the amounts of the individual fatty acids from the cerumen of either group. PMID- 2323083 TI - Hearing disability and hearing aid benefit related to type of hearing impairment. AB - This study was designed to investigate whether patients with a conductive hearing impairment derive more benefit from the provision of a hearing aid than comparable individuals with a sensorineural hearing impairment. A secondary aim was to assess the relative hearing disability of those with each type of impairment. Twenty-eight patients with a bilateral, symmetrical conductive impairment were selected. They were matched for age, sex and speech frequency average to individuals with a bilateral, symmetrical sensorineural hearing impairment. Each patient performed free-field audio and audio-visual tests in noise, both with and without a hearing aid, during which the non-test ear was acoustically occluded. When unaided, individuals with a conductive impairment were more disabled than those with a sensorineural impairment. On the other hand, those with a conductive impairment derived more benefit from an aid than those with a sensorineural impairment. PMID- 2323084 TI - Prognosis in laryngeal carcinoma: tumour factors. AB - A personal series of 765 previously untreated patients with laryngeal carcinoma seen between 1962 and 1988 was analysed for the importance of prognostic factors. There were numerous significant correlations between tumour prognostic factors, particularly with neck node status. Palpable cervical nodes increased in frequency with increasing T status, and palpable lymph nodes were commoner in less well differentiated tumours, and in supra and sub-glottic tumours. These correlations were very highly significant. Increasing T stage was associated with increasing N stage. T stage was also associated with site, glottic tumours being far more likely to be T1 than supra or sub-glottic tumours. T stage was not related to histological grade. Histological grade correlated with site, glottic tumours being well differentiated much more often. When survival was analysed by univariate methods there were highly significant differences with increasing T stage and N stage, between the various histological grades and the various sites. However, when survival was analysed by multifactorial methods taking interactions into account, only N status was a significant prognostic factor. When patients with palpable nodes submitted to surgery were analysed, it transpired that clinical staging and node level were relatively unimportant compared with pathological findings: both the number of nodes invaded and the presence of tumour outside lymph nodes (extracapsular rupture) were highly significant. PMID- 2323085 TI - A double-blind, randomized, prospective trial of a topical antiseptic versus a topical antibiotic in the treatment of otorrhoea. AB - The clinical efficacy was assessed of a topical antiseptic (aluminium acetate) and a topical antibiotic (gentamicin sulphate) for the initial treatment of otorrhoea. Evidence of resistant organisms developing to either treatments after 9 and 21 days was also examined. 139 affected ears were entered into the trial and of these, 102 (74%) completed the study. Improvement in the otorrhoea occurred in 68% of ears treated with gentamicin and 67% of ears treated with aluminium acetate, with no significant difference between the two treatments. No resistant organisms to aluminium acetate were encountered. Twelve gentamicin treated ears had gentamicin-resistant organisms at presentation and one patient developed a gentamicin-resistant Pseudomonas during treatment. We therefore recommend a topical antiseptic such as aluminium acetate rather than a topical antibiotic in the initial treatment of otorrhoea on the grounds of cost, avoidance of resistance and toxicity. PMID- 2323086 TI - Proximal 15q variant as possible pitfall in the cytogenetic diagnosis of Prader Willi syndrome. AB - A patient with Prader-Willi syndrome showed an elongated proximal 15q, and thus was initially considered to be negative for a proximal 15q deletion. However, repeated high resolution chromosome study demonstrating the DNA-replication banding patterns revealed an obvious deletion/deficiency of the 15q12 equivalent band on that elongated chromosome 15. This deletion was further verified by comparison with the parental chromosomes 15 and the deleted chromosome 15 was of paternal origin. The elongation was due to a long variant of 15q11.2 band, which has previously been shown to be polymorphic/variable. This variable proximal 15q site could potentially mask a deletion if it is too long, or mimic a deletion if it is too short. The use of the DNA-replication banding technique instead of the more widely used trypsin banding technique could alleviate this possible pitfall. PMID- 2323087 TI - The common fragile site in band q27 of the human X chromosome is not coincident with the fragile X. AB - The common fragile site on the end of the long arm of the human X chromosome has been shown to be at a different location from the rare fragile site which produces the fragile X syndrome of intellectual handicap. The different locations can be clearly seen in chromosomes at about the 550 band level of resolution. This finding should help resolve difficulties in fragile X cytogenetics where expression of the common fragile site can lead to false positive diagnoses. PMID- 2323088 TI - Comparison of anatomical location of squamous cell carcinoma within the oral cavity and oropharynx with the incidence of in vitro hyperdiploidy. AB - The anatomical location of the squamous cell carcinoma (SCCA) within the oral cavity and oropharynx influenced the association of SCCA with the biomarker in vitro hyperdiploidy in human dermal fibroblast cultures (IVH). There was a strong association of IVH with the occurrence of SCCA in the anterior 2/3 of the tongue, floor of the mouth and lower alveolar ridge of the oral cavity and in the base of the tongue and pharyngeal wall of the oropharynx. There was a lower association of SCCA with IVH in the tonsillar region of the oropharynx. IVH showed no association with SCCA located in other anatomical parts of the oral region. The patient group whose diagnosis of SCCA in the anterior 2/3 of the tongue occurred prior to the age of 50 years were invariably IVH-, whereas those diagnosed after the age of 50 years were IVH+, providing evidence for heterogeneity. There was no such correlation of biomarker subgrouping with age of diagnosis demonstrated for SCCA at any other anatomical location within the oral cavity or oropharynx. PMID- 2323089 TI - A child with cystic fibrosis: I. Parental knowledge about the genetic transmission of CF and about DNA-diagnostic procedures. AB - In 1984, we interviewed 105 Belgian families with a Cystic Fibrosis (CF) child in order to evaluate their knowledge about the genetic aspect of CF. Three years later, in 1987, they received a mailed questionnaire to assess how well they were informed about the new possibilities of DNA diagnosis. In 1984, three out of the four families were aware of their 25% recurrence risk in subsequent pregnancies. The proportion of correct answers rose to 87% in 1987. The risk that relatives may be asymptomatic carriers was less well known. Only 17% knew that the risk that their own brothers and sisters are carriers of the CF-gene was 1 in 2. The probability that their own healthy children would be carriers of the CF-gene was not known at all. Half of the families who returned the questionnaire thought they were well informed about the new possibilities of DNA-analysis for prenatal diagnosis. The limitations of DNA analysis, however, were poorly understood. The information transfer about the genetic transmission of CF and related topics within the family was also investigated. PMID- 2323090 TI - A child with cystic fibrosis: II. Subsequent family planning decisions, reproduction and use of prenatal diagnosis. AB - In 1984, we interviewed 105 Belgian families with a Cystic Fibrosis (CF) child in order to assess the impact of the birth of their CF-child on subsequent family planning and to evaluate their attitudes towards prenatal diagnosis. Three years later, in 1987, they received a mailed questionnaire for an updating of the reproduction data and to assess their knowledge and intentions with regard to the new possibilities of DNA diagnosis. The birth of a CF-child had a major impact upon subsequent family planning. This effect was found both in the reproductive plans reported by the parents and in the occurrence of pregnancies during the follow-up interval. This effect can be attributed mostly to the recurrence risk and consists of postponing pregnancies as well as of deciding against further offspring. If the CF-child was the firstborn, the chance of having another child was greater than if there was already a healthy child before the birth of the CF child. Nevertheless, only 47% of the families in which the CF-child was the firstborn, and who could be followed for an average period of 7 years, had another pregnancy. A large majority of families intended to use prenatal diagnosis should a pregnancy occur. In half of the pregnancies that occurred between 1984 and 1987, a prenatal diagnosis was performed. On the other hand, there is less consensus about pregnancy interruption should prenatal diagnosis reveal an affected fetus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323091 TI - A case of 46,XX,r(X) (p1q1) diagnosed by in situ hybridization. AB - A small marker chromosome was identified as an X-derived ring chromosome by in situ hybridization with a biotinylated X-chromosome specific a-satellite DNA probe. This procedure clearly determined the chromosomal origin of the marker chromosome, which had been impossible to define by conventional cytogenetic techniques including high resolution banding. PMID- 2323092 TI - A linkage study of malignant hyperthermia (MH). AB - Five German families segregating for malignant hyperthermia (MH) were tested for linkage relationships using 35 serological and biochemical markers. Slightly positive lod scores were obtained with MNS, EsD, C3 and P. The relation with the C3 locus on chromosome 19p13.3-13.2 (z = 0.72, theta = 0.11) is of some interest, since genetic linkage of MH with several polymorphic DNA markers from the 19q12 13.2 region has been reported (McCarthy et al. 1989). PMID- 2323094 TI - High resolution banding of an unusual reciprocal translocation in recurrent abortions. AB - Reciprocal translocations involving two chromosomes frequently cause abortion of unbalanced offspring. In many cases, however, meiosis leads to a cytogenetically normal or balanced gamete with normal embryonal development. In a couple investigated because of recurrent reproductive loss, the husband had a reciprocal exchange of parts of the long arms of chromosomes 9 and 10 in the form of inverted insertions. Due to difficulties in obtaining regular homologous pairing during zygotene, this anomaly might not be compatible with cytogenetically normal or balanced offspring. The diagnosis of this translocation was possible using a previously published alkaline Giemsa G-banding technique. PMID- 2323093 TI - Sotos syndrome and de novo balanced autosomal translocation (t(3;6)(p21;p21)) AB - In this report we describe a 6-year-old boy with Sotos syndrome and a de novo apparently balanced 3/6 translocation (karyotype: 46,XY,t(3;6)(p21;p21)). Pre- and postnatal overgrowth are observed in an increasing number of conditions of variable etiology. In the Sotos syndrome autosomal dominant inheritance with variable expression has been documented. Here we discuss the importance of the cytogenetic findings and postulate a relationship between the invisible loss of chromosomal material at 3p21 and/or 6p21 and the expression of the autosomal dominant gene. PMID- 2323095 TI - Three-generation transmission of Hirschsprung's disease. PMID- 2323096 TI - Monosomy X found at first trimester CVS: a diagnostic and counselling dilemma. PMID- 2323097 TI - Terminal 7q deletion as a cause of holoprosencephaly. PMID- 2323098 TI - Monoclonal antibodies to early pregnancy factor perturb tumour cell growth. AB - The pregnancy-associated substance early pregnancy factor (EPF) has previously been reported as a product of tumours of germ cell origin. More recently EPF (or an EPF-related substance, tEPF) has also been detected in the serum of patients bearing tumours of non-germ cell origin. We report here the production of tEPF by a variety of cultured transformed and tumour cell lines, of both germ and non germ cell origin. Antibodies specific for EPF remove all tEPF activity from tumour cell conditioned medium. tEPF production is found to be associated with cell division; tEPF is no longer detected after growth arrest or differentiation. Co-culture of tumour cells with increasing doses of anti-EPF monoclonal antibodies resulted in a significant, dose-dependent decrease in rate of cell growth and viability. Similar anti-EPF concentrations had no effect on the concanavalin A induced proliferation of mouse spleen cells. These studies suggest, therefore, that tEPF is a growth-regulated product of cultured tumour and transformed cells. These cells are also dependent upon tEPF for continued growth, i.e. tEPF is acting in the autocrine mode. PMID- 2323099 TI - IgG isotype and isotype specificity of murine monoclonal IgG rheumatoid factors. AB - Immune complexes of lipopolysaccharide (LPS) with homologous IgG antibody induces rheumatoid factor (RF) predominantly of the IgG class in normal mice, while LPS alone induces mostly IgM RF directed to homologous IgG1. In this study, IgG monoclonal RFs (mRF) were prepared from hybridomas derived from spleen cells of BALB/c mice which were immunized with complexes of TNP-LPS with anti-TNP mouse IgG and their specificity to mouse IgG subclasses was assessed by analysing dissociation kinetics of the ligands due to RF-specific and non-specific interactions. Of the 19 IgG mRFs (11 IgG1, five IgG2a, one IgG2b and two IgG3 types) tested, 14 were directed to either IgG3 or IgG2b or both, while only one exhibited a significant binding capacity to IgG1. Other mRFs, although reactive to rabbit IgG, exhibited little homophilic activity. None of these mRFs reacted strongly with their own isotypes. The results suggest that the IgG RF producing cells are not direct progenies of the IgG1-directed IgM RF-producing cells but may have developed via a rigorous selection process to eliminate clones that produce self-reactive RF. PMID- 2323100 TI - Soluble histocompatibility antigens in synovial fluids of patients with rheumatoid arthritis. AB - Soluble histocompatibility antigens of the class II region have been detected in synovial fluids obtained from patients with rheumatoid arthritis. A capture immunoassay involving two monoclonal antibodies was used; interference by rheumatoid factor, which is a feature of such assays, was overcome by mild pretreatment of fluids with 2-mercaptoethanol. No HLA class II antigen could be detected in matched sera from patients, even when levels were high in synovial fluids. Released HLA-class II material was of high molecular weight (greater than 1000 kD) and was linked to HLA-class I antigen. However, no significant amounts of other common cell surface antigens were detected in the complex, suggesting a preferential release of MHC antigens from cells of the inflamed synovium. Attempts to induce production of similar material from a cell line which expresses HLA class II strongly at the cell surface, by stressing the cells in various ways did not succeed, indicating that release is an active process. PMID- 2323101 TI - Anti-thyroglobulin autoantibodies in sera from patients with chronic thyroiditis and from healthy subjects: differences in cross-reactivity with thyroid peroxidase. AB - A significant portion (about 12.7%) of healthy subjects was found to contain anti thyroglobulin (anti-Tg) antibodies in their sera. We compared the binding activities of these antibodies and of anti-Tg autoantibodies from sera of patients with chronic thyroiditis with human thyroid peroxidase (TPO). The results obtained by ELISA indicated that out of 10 healthy subjects with anti-Tg antibodies, only four had anti-Tg antibodies capable of binding to TPO, whereas anti-Tg autoantibodies from almost all patients with chronic thyroiditis possessed high binding activities to TPO. By use of the immunoprecipitation method, it was also shown that although all anti-Tg autoantibodies from patients precipitated TPO, a majority of anti-Tg antibodies from healthy subjects could not precipitate TPO. Such findings cannot be ascribed to the differences in levels of anti-Tg autoantibodies and anti-TPO autoantibodies in sera and the differences in avidities of anti-Tg antibodies in sera between healthy subjects and patients with chronic thyroiditis. Thus, it can be concluded that anti-Tg antibodies from healthy subjects differ from those of patients with chronic thyroiditis with respect to TPO binding, probably due to difference in fine specificities of these anti-Tg antibodies. PMID- 2323102 TI - Parasite antigens recognized by patients with cutaneous leishmaniasis. AB - Humoral and cell-mediated responses to crude and purified parasite antigens were examined in patients with active cutaneous leishmaniasis caused by Leishmania major. The patients had serum antibody titres against parasite lysates ranging from 1/500 to 1/10,000 and recognized multiple components by Western blotting with molecular weights between 5000 and greater than 200,000. Several components, particularly at 5 and 50 kD, were recognized by most of the patients. The lymphoproliferative responses to two pure antigens, promastigote surface protease and lipophosphoglycan, both considered potential candidates for the development of a human vaccine were measured. No response to promastigote surface protease was observed even at 10 micrograms/ml; however, weak proliferation to lipophosphoglycan was consistently present. T cell blots examining peripheral blood lymphocyte proliferation, showed antigen-specific responses to a 72-82 kD component in promastigote lysates. PMID- 2323103 TI - Serum sickness and acute renal failure after streptokinase therapy for myocardial infarction. AB - A patient developed serum sickness and acute renal failure following therapy with streptokinase for myocardial ischaemia. There was a previous history of a cellulitic infection of the leg, and antibodies to streptokinase were measurable in a serum sample taken from the patient before therapy. A cryoglobulin was detected at the time of presentation with serum sickness. This contained polyclonal IgG (with anti-streptokinase activity), streptokinase, and C3. Circulating immune complexes were demonstrated by C1q-binding assay. Deposition of C3 was observed in skin and renal biopsies, and bound to erythrocytes. Renal histology, however, showed acute tubular necrosis, with no vasculitis or inflammatory cell infiltrate. This case provides an unusual example of the characterization of an immune complex comprising a specific antibody and an exogenous antigen, and has clinical implications for the use of streptokinase. PMID- 2323104 TI - Lymphokine-activated killer cytotoxicity against leukaemic blast cells. AB - While the sensitivity of cell lines and solid tumours to lymphokine-activated killer (LAK) cell cytotoxicity is extensively reported, the ability of these generated cytotoxic cells to lyse leukaemic blast cells is controversial. This study reports the successful generation of LAK cells with specificity for leukaemic blast cells. Control donors, patients in remission and patients with active leukaemia were capable of lysing allogeneic leukaemic blast cells. One patient was also capable of lysing autologous leukaemic blast cells. Successful LAK generation was achieved by the use of high dose recombinant interleukin-2 (rIL-2) while combinations of lymphokines did not improve LAK specificity or efficacy. These findings suggest that LAK immunotherapy may be considered for the treatment of patients with acute leukaemia. PMID- 2323105 TI - Anti-class II beta-chain antibodies in the serum and synovial fluid of rheumatoid arthritis patients. AB - Sera and synovial fluid (SF) from rheumatoid arthritis (RA) patients were evaluated for anti-HLA class II beta-chain antibodies using single and two dimensional immunoblots. The antibodies from RA sera and SFs which reacted with class II beta-chain determinants were predominantly IgM and IgA with minimal IgG. This reactivity was also present in SFs from other rheumatic diseases. Anti-class II beta-chain antibodies were also shown to be present simultaneously in RA sera and SF. PMID- 2323106 TI - Expression of IgM and IgG autoantibodies in pediatric and adult systemic lupus erythematosus. AB - To compare patterns of autoantibody responses in pediatric and adult patients with systemic lupus erythematosus (SLE). IgG and IgM antibodies to single stranded DNA (ssDNA), Sm, and the 70-kDa protein component of the RNP antigen (70 kDa RNP) were measured in 29 pediatric and 36 adult patients by enzyme-linked immunosorbent assays. Antibodies of either isotype to ssDNA, Sm, and 70-kDa RNP were present in 64, 58, and 79% of pediatric patients, respectively, comparable to prevalences of these autoantibodies in the adult SLE patients. Pediatric SLE patients were more likely than adult patients to have IgM anti-Sm antibodies (41.4% vs 13.9%, P = 0.02) and tended to more commonly express IgM anti-70-kDa RNP and IgM anti-ssDNA antibodies. The prominence of IgM autoantibody responses among pediatric SLE patients was shown by multiple logistic regression analysis to be related to total IgM concentrations and not related to age or duration of disease. Sequential serum samples available from several pediatric patients revealed the maintenance of similar patterns of isotype responses over time in approximately one-half of patients. In those patients whose responses changed over time, the variations in isotype expression were consistent with maturation of antibody responses of each specificity. While these results demonstrate similarities in autoimmune reactivities between pediatric and adult SLE patients, the serologic study of pediatric patients may provide an opportunity to more readily investigate the evolution of autoantibody responses. PMID- 2323107 TI - HLA-DP+ T cells and deficient interleukin-2 production in patients with systemic lupus erythematosus. AB - In patients with systemic lupus erythematosus (SLE), frequency of the T cells positive for HLA-DP, one of the major histocompatibility complex (MHC) class II molecules, was markedly increased in peripheral blood lymphocytes (PBL), in association with an increase in the amount of specific cytoplasmic transcript of the HLA-DP gene segment. Cell cycle analysis showed that HLA-DP is an early activation marker of T cells and that the high ratios of HLA-DP+ T cells from SLE patients are associated with high frequency of T cells at early activation phases, mainly of G1A. Initial high ratios of HLA-DP+ T cells decreased to a great extent during 4 days of in vitro culture, in the absence of mitogens. This event was associated with decreases in the amount of HLA-DP transcript and the disappearance of activated T cells. Studies on the interleukin 2 (IL-2) production of T cells from patients with SLE demonstrated that while the PBL rich in HLA-DP+ T cells show a markedly low production of IL-2, preculture of these PBL restores the ability to produce IL-2. Thus, it appears that the T cells in patients with SLE are essentially intact with regard to the capacity to produce IL-2 and that T cell activation events continuously occurring in SLE patients are related to a deficiency in IL-2 production. The possible underlying mechanisms are discussed. PMID- 2323108 TI - In vitro and in vivo production of interleukin-6 by fetal mononuclear cells. AB - We examined the functional activity of cord mononuclear cells (MNCs) to produce interleukin (IL)-6 in vitro and in vivo. We stimulated fetal T-cell, B-cell, and macrophage fractions with mitogens. The supernatant of each stimulated cord cell fraction contained a comparable amount of IL-6 to that of each adult cell fraction activated similarly, suggesting functional maturity of cord MNCs' ability to produce IL-6. We then examined fetal cells' activities to produce IL-6 in response to perinatal infections, especially to intraamniotic infections (IAI). Among the cord MNCs from fetuses with IAI, macrophages were major cells producing IL-6. The serum IL-6 level in the fetuses with IAI was elevated, but it decreased to normal levels after antibiotic treatment; this finding indicates that IL-6-mediated host defense mechanisms by cord MNCs are triggered by perinatal infections. PMID- 2323109 TI - Spontaneous proliferation of peripheral mononuclear cells in natural measles virus infection: identification of dividing cells and correlation with mitogen responsiveness. AB - Spontaneous proliferation of peripheral mononuclear cells is pronounced following measles virus infection at a time when patients mount effective humoral and cell mediated immune responses and manifest a range of poorly understood immunologic abnormalities. We found spontaneous activity (measles 8000 +/- 1200 cpm vs control 1900 +/- 350 cpm; P less than 0.05) to wax and wane abruptly during the first week after the rash in parallel with expression of the lymphocyte activation marker OKT10. At peak activity, approximately 10% of circulating mononuclear cells were actively synthesizing DNA. Double labeling of individual mononuclear cells with autoradiography and immunoperoxidase demonstrated that B and T lymphocytes as well as monocytes participate in the spontaneous activity. Proliferative activity was increased 3- to 20-fold over control levels in all PBMC subsets such that close to one-third of circulating B cells and monocytes and 5-10% of CD4- and CD8-positive T cells were preparing to divide. Mitogen responsiveness was generally decreased in measles patients (58,800 +/- 4600 cpm vs control 97,700 +/- 15,500 cpm; P less than 0.002). Neither spontaneous proliferation nor mitogen responsiveness was correlated with age, sex, or the presence of complications. Patients with the lowest mitogen responses, however, had the greatest increases in B cell (P less than 0.03) and CD8-positive T cell (P less than 0.05) proliferation. These data demonstrate that all major immunologic cell types proliferate in response to measles virus infection. Mechanisms by which spontaneous proliferative activity in individual mononuclear subsets could contribute to depressed mitogen responsiveness are discussed. PMID- 2323110 TI - Long-term prognosis of focal sclerosing glomerulonephritis. An analysis of 250 cases with particular regard to tubulointerstitial changes. AB - The following results were obtained in a long-term retrospective study including 250 patients with focal sclerosing glomerulonephritis: 1. The renal survival rate (RSR) was 90% at 5 years and 67% at 10 years, the average period of observation being 4.7 years. 2. Univariate analysis revealed that the following morphologic and clinical parameters are associated with an increased risk of terminal renal failure or death due to renal causes: a) Tubulointerstitial changes in the form of interstitial fibrosis, with or without acute renal failure; b) Advanced glomerular lesions; c) Advanced vascular alterations; d) Nephrotic syndrome present at the time of the biopsy; e) Elevated serum creatinine concentration at the time of the biopsy; f) Arterial hypertension at the time of the biopsy; g) Greater age at diagnosis; h) Male sex. 3. Multivariate survivorship analysis showed that tubulointerstitial changes and the presence of nephrotic syndrome at the time of biopsy are the only variables with significant independent predictive value for the outcome. Assessment of these factors thus allows the pathologist to make a relevant statement concerning the probable course and prognosis of the disease at the time of the diagnostic biopsy. PMID- 2323111 TI - Urinary excretion of dipeptidyl aminopeptidase i.v. in patients with renal diseases. AB - Enzymuria is a frequent finding in patients suffering from various kidney diseases. The present study was undertaken to evaluate the clinical value of the determination of tubule-brush-border-associated dipeptidyl aminopeptidase IV (DAP IV) in the urine of patients with acute and chronic tubulointerstitial nephritis (n = 12), chronic glomerulonephritis (n = 15), essential arterial hypertension (n = 30), after kidney transplantation (n = 20), and of healthy control persons (n = 68). DAP IV was measured in spontaneously voided mid-stream morning urine ("second morning urine"), and was expressed as enzyme activity in units/liter. In order to account for variations due to urine concentration without collecting 24 hour specimens, a urinary DAP IV/creatinine ratio (DCR) was calculated. Furthermore, patterns of proteinuria were assayed by SDS-polyacrylamide gel electrophoresis. Urinary DAP IV activity of healthy controls was 4.94 +/- 0.12 U/l (DCR: 0.46 +/- 0.30 U/mmol creatinine) with only small day to day variations. Urinary DAP IV activity in patients with tubulointerstitial nephritis was significantly higher (15.5 +/- 15.6 U/l, p less than 0.05 vs controls; DCR: 1.67 +/- 0.97 U/mmol creatinine, p less than 0.001 vs controls). In patients with chronic glomerulonephritis urinary DAP IV activity was 9.6 +/- 5.6 U/l, p less than 0.05 (DCR: 1.22 +/- 0.75 U/mmol creatinine, p less than 0.05 vs controls). Increased urinary DAP IV activity in patients with chronic glomerulonephritis was associated with a mixed glomerulo-tubular pattern of proteinuria (as determined by SDS-PAGE).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323112 TI - Red cell volume distribution curves in the diagnosis of glomerular and non glomerular hematuria. AB - It has been suggested that measurement of red blood cell (RBC) volume, by red cell analyzers (RCA), may be used to distinguish glomerular from non-glomerular hematuria. The RCA measures all urinary particles, including RBC. We found that red cell volume distribution curves (RVDC) obtained with a Coulter S+IV RCA were non-specific in predicting the cause of hematuria. Normal RBC added to urine at about 15,000/mm3 produced the expected non-glomerular RCVDC but at decreasing RBC concentrations mixed and then glomerular RCVDCs were found. Urine from 7 normal subjects (6 without urinary RBC) showed particle volume distribution curves identical to glomerular RCVDC. These urinary particles were examined by scanning electron microscopy (SEM) after filtration (3 microns and 0.8 micron pore size). Hematuric urine from a patient after prostatectomy contained RBC (3.5-9.5 microns diameter) and particulate debris (1.0-7.5 microns diameter). Similar results were obtained for a patient with crescentic glomerulonephritis (particles 1-13 microns diameter). Attempts to separate glomerular urinary RBC from debris by centrifugation against a sucrose polymer were unsuccessful. The shape of the RCVDC obtained with RCA is altered by the presence of debris in urine. The true MCV of glomerular RBC is still unknown. The usefulness of RCA in the diagnosis of hematuria is limited to patients with large numbers of urinary RBC. PMID- 2323113 TI - Retreatment of membranous nephropathy with steroids and chlorambucil after initial unresponsiveness to alternate-day prednisone. PMID- 2323114 TI - Comment on "Concurrent Focal Segmental Glomerulosclerosis and Membranous Nephropathy" by Amenta et al. PMID- 2323115 TI - Prophylactic immunoglobulin (IgG) infusions in infants. PMID- 2323117 TI - Clinical trials: do they change clinical practice? PMID- 2323116 TI - Cyclosporin induced hyperuricemia and gout. PMID- 2323118 TI - Radionuclide assessment of left ventricular function during dobutamine infusion in patients with coronary artery disease: comparison with ergometer exercise. AB - The effects of dobutamine on left ventricular function were assessed employing radionuclide ventriculography (RNV) in 7 normal subjects (Group 1) and 21 patients with coronary artery disease (Group 2). After routine bicycle ergometer exercise RNV, dobutamine infusion was started at 5 micrograms/kg/min and the dosage was increased by 5 micrograms/kg/min every 4 minutes to a total of 15 micrograms/kg/min. In Group 1, left ventricular ejection fraction (LVEF) increased by both ergometer exercise and dobutamine infusion. In Group 2, LVEF did not increase during exercise, but increased during dobutamine infusion without evidence of significant myocardial ischemia. Only 2 patients in Group 2 had new regional wall motion abnormality. Left ventricular end-diastolic volume (LVEDV) in Group 2 increased from 191 +/- 19 to 210 +/- 18 ml during ergometer exercise, but decreased from 193 +/- 18 to 153 +/- 19 ml during dobutamine infusion. Short-term low-dose infusion of dobutamine may be used in patients without evidence of significant myocardial ischemia, but probably cannot be substituted for exercise testing in patients with mild to moderate coronary artery disease. PMID- 2323119 TI - Value of notching and slurring of the resting QRS complex in the detection of ischemic heart disease. AB - The resting 12-lead ECG has long been known to be an insensitive marker of underlying ischemic heart disease (IHD). The purpose of this study was to determine if QRS complex notching and slurring is of significant value as a diagnostic discriminator in the detection of IHD. The data from 205 consecutive patients coming to cardiac catheterization for evaluation of probable IHD were initially analyzed. Eighty-three patients were excluded based upon ventricular hypertrophy, bundle-branch block, lack of data, and pacemaker rhythm. The balance, 122 patients (mean age 61.7 years), were evaluated for angiographic evidence of IHD, ECG findings of QRS notching or slurring, and abnormal Q waves. The data revealed a high prevalence of QRS notching or slurring; 62.2% in those patients with IHD, double the prevalence of significant Q waves (33.3%). The two markers had an approximately equal prevalence (QRS notching or slurring 61.7% vs. Q waves 53.2%) in patients with angiographic evidence of infarction; however, in patients with less than infarct criteria for IHD, the prevalence of QRS notching or slurring was 62.8%, while only 11.6% showed abnormal Q waves. Analysis indicated that QRS notching or slurring has a sensitivity of 62.2% and a specificity of 93.8% for the detection of IHD. The study demonstrates that QRS notching or slurring is a moderately sensitive and a very specific marker of ischemic heart disease in selected patients when using the resting ECG, and is of greatest value in those patients with lesser degrees of ischemic myocardial injury where the prevalence of Q waves is low. PMID- 2323120 TI - Clinical approach to paroxysmal atrial fibrillation. AB - In addition to the role of the electrophysiological substrate, paroxysmal atrial fibrillation depends on the modulation of the atrial tissues by the autonomic nervous system. Experimentally, models of atrial fibrillation can be based on either adrenergic or vagal stimulations that provoke the arrhythmia by disturbing in a different way conduction and refractory periods of the atrium. Clinically, the role of the autonomic nervous system can be suspected from the clinical history, and paroxysmal attacks can typically be observed either at daytime or at night, at exercise or at rest. Careful attention should be paid to the changes of heart rate that occur in the minutes or tens of minutes prior to the attacks, and the trend of acceleration or slowing of cardiac frequency observed in Holter tracings provides reliable indications of the state of the vago-sympathetic balance in these patients. During the attacks, the electrocardiographic aspect of atrial flutter alternating with a pattern of atrial fibrillation is typical of vagally dependent arrhythmias, whereas atrial tachycardia is more frequently observed at the onset of adrenergic atrial fibrillation. When the paroxysmal forms of arrhythmia are resistant to usual pure antiarrhythmic therapy including type IA agents and flecainide or encainide, one should take into account the role of the autonomic nervous system. Propafenone, or beta-blockers combined with type I drugs, are very effective every time an adrenergic factor is involved, but prevent the beneficial role of other agents if a vagal mechanism is predominant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323121 TI - Repeat determination of left ventricular wall thickness from mass and volume during one cardiac cycle for the calculation of left ventricular wall stress parameters. AB - Left ventricular end-diastolic wall stress, end-systolic wall stress, and systolic stress-time integral are important parameters to characterize left ventricular load and function. To obtain these parameters, left ventricular pressure, volume, and wall thickness data must be determined at short time intervals throughout one cardiac cycle. However, the measurement of wall thickness at short intervals (i.e., 20 ms) throughout a cardiac cycle is tedious. Furthermore, measurements of wall thickness are less accurate at end-systole compared with end-diastole. For these reasons we developed a computer program for calculating wall thickness at short intervals (20 ms) throughout the cardiac cycle from one single determination of left ventricular wall mass and repetitive measurements of left ventricular (LV) volume. PMID- 2323122 TI - Coronary arterial morphology 10 years after "endarterectomy". AB - Little information is available regarding coronary artery morphology after endarterectomy. In this report, we describe coronary artery morphology seen at necropsy 10 years after coronary artery endarterectomy and compare it with the morphology of the original endarterectomy specimen. Surprisingly, in some areas, all of the internal elastic membrane and most of the media were observed in the "endarterectomy" specimen. PMID- 2323123 TI - Ascending aortic dissection complicating syphilitic aortitis, late after aortic valve replacement. AB - A 54-year-old man underwent aortic valve replacement for syphilitic aortic regurgitation. Eight years later, he was admitted with sudden precordial discomfort and symptoms of superior vena caval obstruction. Ascending aortic dissection was diagnosed by echocardiography and computed tomography of the thorax. The patient succumbed rapidly after admission. Postmortem findings and histological features were compatible with syphilitic aortitis, without significant atherosclerosis. This case report adds to the sparse literature on aortic dissection complicating syphilitic aortitis, and illustrates that, at certain stages of the disease process, syphilitic aortitis can lead to such a degree of mechanical instability of the aortic wall as to predispose to dissection. PMID- 2323124 TI - Acute myocardial infarction associated with intravenous dipyridamole for rubidium 82 PET imaging. AB - This report describes the occurrence of chest pain and electrocardiographic features of acute myocardial infarction following intravenous dipyridamole handgrip stress. Myocardial perfusion imaging (Rb-82 PET) demonstrated a stress induced perfusion defect. Following failure to respond to medical therapy, urgent cardiac catheterization demonstrated total occlusion of the left anterior descending coronary artery. The vessel was revascularized, with limitation of myocardial damage evidenced by failure to develop anterior Q waves and only modest elevation of cardiac enzyme levels. Complications of intravenous dipyridamole stress are rare, this case constituting the first major problem in over 500 such procedures at this institution. However, this experience demonstrates the importance of vigilant observation during the performance of this technique. PMID- 2323125 TI - Symposium: The rotator cuff. PMID- 2323126 TI - Contracture of the shoulder. AB - A retrospective study involving 2027 patients with a limited range of motion of the shoulder in the period from 1970 to 1987 is described. Of these, 1219 patients (60%) were diagnosed as having frozen shoulder, with the highest incidence occurring in patients aged 50-60 years. The mechanism involved in the contracture is complicated. At first, the movement of the greater tuberosity at the subacromial level (also called the subacromial secondary joint) is limited due to bursitis. The external rotation of the upper arm then decreases, and the long rotator muscles contract. The relationship between the cause of contracture and the direction of the decreased mobility was analyzed. A ratio of the degree of external rotation with the arm beside the body to that achieved with the arm elevated to the horizontal plane showed values of almost one to one. Conservative treatment including physiotherapy, local anesthetic block, and joint distension must be attempted in all patients. If the conservative treatment remains ineffective, the surgical procedure should be considered. Satisfactory clinical results of arthroplasty of the subacromial joint were obtained in patients with frozen shoulder. PMID- 2323127 TI - Posterior interosseous nerve syndrome associated with rheumatoid synovial cysts of the elbow joint. AB - Three rheumatoid arthritis patients developed synovial cysts of the elbow joint and an acute compression neuropathy of the posterior interosseous nerve. All patients had weakness of the finger extensors; in one the extensor tendons were explored before the exact diagnosis was made. Intraarticular steroid injections were effective in one patient. In the other two patients surgical decompression of the radial nerve and elbow synovectomy with radial head resection were curative. Although relatively rare, the diagnosis of an antecubital cyst must be considered when complications such as a nerve compression syndrome are present. PMID- 2323128 TI - Walking efficiency after cemented and noncemented total hip arthroplasty. AB - Clinical evaluation using the Harris hip score has been supplemented with analysis of walking capacity before and after total hip arthroplasty (THA). Twenty patients were studied, ten of whom were treated with a cemented Charnley prosthesis and ten with a noncemented HP-Garches prosthesis. Tests were performed preoperatively and three, six, and 12 months postoperatively. Harris hip scores increased from a mean of 35 points preoperatively to 85 one year after surgery. Patients with a Charnley prosthesis had significantly higher scores than those with an HP-Garches prosthesis. The hip score did not differ between patients with uni- and bilateral disease. Mean maximum walking speed before surgery was 62 m/minute and increased to 80 m/minute one year after THA. The mean oxygen cost preoperatively was 0.267 ml/kg/m and decreased to 0.221 ml/kg/m one year after surgery. A weak correlation was found between differences in Harris hip scores and the corresponding oxygen cost. The onset of and the recovery from complications as well as differences between patients with uni- and bilateral diseases were reflected in changes in oxygen cost in contrast to clinical scores. The measurement of oxygen cost gave objective and valuable information about walking efficiency after THA. PMID- 2323129 TI - Clinical and roentgenographic evaluation of bipolar prostheses with noncemented anatomic medullary locking femoral stems. AB - Fifty-six DePuy anatomic medullary locking femoral bipolar prostheses were reviewed clinically and roentgenographically in 50 patients at an average follow up period of 30 months (range, 24-71 months). Forty-four of the implantations were in 40 male and 12 were in ten female patients. Forty-five devices were placed in primary operations, while 11 were used in revisions. The overall average age was 53.5 years. The average Harris hip scores for the primary bipolars were 29.8 preoperative and 77.3 postoperative, while the revision bipolars had Harris hip scores of 35.9 preoperative and 75.1 postoperative. Nearly one-half (47%) of all primary and 54% of the revision patients experienced pain to some degree on ambulation. Roentgenographically, all femoral components appeared to be well fixed biologically. Roentgenographic changes occurred with time in both primary and revision prostheses. On roentgenographic zonal analysis of primary prostheses, radiolucencies greater than 1 mm were present most frequently in the most proximal lateral zone and at the distal tip of the prosthesis. Although the use of noncemented bipolar prostheses generally shows acceptable clinical results, noncemented fixed acetabular components with noncemented femoral components produce a more satisfactory clinical result. PMID- 2323130 TI - Biomechanical analysis of the Chiari pelvic osteotomy. Preserving hip abductor strength. AB - Although the Chiari osteotomy is usually effective in reducing pain, many patients are left with a long-term limp. The postoperative limp can at times be caused by hip abductors that have strength insufficient to counteract the torque from body weight during single-leg stance. To study how the surgical technique affects the hip abductor muscles, a biomechanical model was developed that computes the postsurgery pelvic geometry and the resulting hip abductor torque given three surgical parameters: angulation of the osteotomy, distance of medical displacement, and angle of internal rotation. The computer simulations of the Chiari osteotomy showed that some sets of surgical parameters conserve abductor torque while others greatly reduce it. Simulated surgeries with high angulation and large medial displacement reduce gluteus medius abductor torque by up to 65%. Therefore, this combination of surgical parameters may account for some instances of the postoperative limp. In the model, high angulation reduces the length of the gluteus medius and is the primary cause of reduced abductor strength. Simulated horizontal osteotomies (0 degrees to 10 degrees) were found to best conserve both muscle length and abductor torque. PMID- 2323131 TI - Acetabular protrusion in thalassemia. A report of four cases. AB - Four female patients with thalassemia intermedia developed secondary acetabular protrusion. These cases could be the first reported cases of nontraumatic acetabular protrusion in patients with thalassemia. The rarified pelvic bone may be due to medullary hyperplasia, iron overload, or disordered calcium metabolism in conjunction with osteomalacia. The fact that currently patients with beta thalassemia have a longer life expectancy may explain the recent observation of this entity, which should become more familiar to orthopedic surgeons who treat thalassemia patients in the future. PMID- 2323132 TI - Complications of Pemberton's pericapsular osteotomy. A report of two cases. AB - Pemberton's pericapsular osteotomy has been performed since 1970 at the authors' institution on 56 hips in 49 patients. Two complications, obturator dislocation and osteonecrosis of the femoral head, occurred. A ten-year-old girl had an obturator dislocation that was recognized six weeks postoperatively. This dislocation probably occurred because the reduction of the acetabular dysplasia and the varus osteotomy were excessive in degree. Osteonecrosis of the femoral head was recognized in a 13-year-old girl six weeks postoperatively. This complication probably occurred because too much pressure was imposed on the femoral head, which had been dislocated for a long time and whose circumstances changed suddenly. PMID- 2323134 TI - A simplified approach to the tibial attachment of the posterior cruciate ligament. AB - The standard approach through the popliteal fossa to the tibial attachment of the posterior cruciate ligament (PCL) can be time-consuming and is regarded as hazardous. The simplified approach does not transect or expose neurovascular structures as in other procedures. With dissection on the medial border of the medial head of the gastrocnemius and by lateral retraction, the posterior capsule is safely exposed. The approach is ideal for internal fixation of an avulsed tibial attachment of the PCL. PMID- 2323133 TI - Dislocation/subluxation of meniscal bearing elements after New Jersey low-contact stress total knee arthroplasty. AB - From October 1985 to April 1986, 43 consecutive New Jersey low-contact stress total knee arthroplasties (TKAs) were performed for degenerative arthritis of the knee. At the one-year follow-up examination, 91% of the patients had good to excellent results based on the Hospital for Special Surgery scoring system. Four patients, however, sustained dislocation/subluxation of the meniscal bearing elements. Three of these occurred within 13 days postoperatively, and one patient sustained a dislocation at six months postoperatively. These four patients were treated with revision TKA. Despite following the precise technique in performance of this procedure, a 9.3% incidence of dislocation/subluxation of the meniscal bearing elements occurred. PMID- 2323135 TI - Arthroscopic evaluation of anterior cruciate ligament reconstruction using a free patellar tendon autograft. A prospective, randomized study. AB - In a prospective study, follow-up arthroscopy was performed (with the informed consent of the patient) after anterior cruciate ligament reconstruction using a free patellar tendon autograft. Nineteen of 21 consecutive patients agreed to arthroscopy. Time between operation and arthroscopy ranged from six to 25 months (average, 15 months) and was distributed at random among the patients. In evaluating knee stability and functional performance, the arthroscopic findings were disappointing. The Lysholm score improved from 68 +/- 8 points preoperatively to 84 +/- 8 points postoperatively. KT-1000 measurement on the day before follow-up arthroscopy showed only a slightly increased anterior laxity of 6.2 mm compared to 4.7 mm on the uninjured side. When the arthroscopic results were graded from 0 (ruptured) to 3 (excellent), four patients had a Grade 3 result, ten patients had a Grade 2 (moderate) result, and five patients had a Grade 1 (poor) result. No graft was ruptured. These findings indicate that, in the majority of patients, reconstruction of the anterior cruciate ligament using a free patellar tendon autograft will not result in an arthroscopically normal substitute for the anterior cruciate ligament. PMID- 2323136 TI - Dislocation of a posterior stabilized total knee prosthesis. A report of two cases. AB - Posterior stabilized knee prostheses have been recommended for knees with posterior cruciate deficiency, as well as for knees with prior patellectomy. Two cases are presented in which a complete dislocation of a Kinematic II Stabilizer prosthesis occurred after primary knee arthroplasty. The mechanism of dislocation was a varus or valgus stress while the knee was flexed. This previously unreported complication of dislocation after primary knee arthroplasty with a posterior stabilized knee prosthesis was, we believe, due, in part, to the design of this prosthesis, which provides little mediolateral stability in flexion, in combination with a mild degree of laxity of the collateral ligaments. This complication could be prevented by use of a prosthesis with greater inherent mediolateral stability. PMID- 2323137 TI - External skeletal fixation versus cement fixation in the treatment of redislocated Colles' fracture. AB - In a prospective investigation in 1984 and 1985, all Colles' fractures (not comminuted or intraarticular) that redisplaced after two closed reductions were allocated at random to one of two groups: Group I (n = 23), in which the dorsal bone deficiency was filled with bone cement (methylmethacrylate), and Group II (n = 25), in which the fracture was treated with external fixation. All were followed for one year and examined with respect to anatomy of the fracture, wrist movement, strength, appearance, pain, function, and complications. Roentgenograms, 12 months after treatment, showed that all fractures had healed and that the cement was enveloped in cortical bone. The final results were equal in the two groups, but Group I improved earlier and had no complications. PMID- 2323138 TI - Streptococcal toxic shocklike syndrome leading to bilateral lower extremity compartment syndrome and renal failure. Report of a case. AB - Compartment syndrome is considered a true emergency in orthopedic practice. To reduce morbidity and mortality from this condition, prompt diagnosis and appropriate treatment are absolutely essential. An unusual bilateral lower extremity compartment syndrome leading to renal failure and crush syndrome occurred in a 13-year-old girl with Streptococcal toxic shocklike syndrome. This situation seems not to have been previously reported. Early diagnosis and expeditious treatment produced minimal sequelae of the condition. PMID- 2323139 TI - Peripheral teflon catheters. Potential source for bacterial contamination of orthopedic implants? AB - To detect low numbers of bacterial cells on Teflon catheters removed from peripheral veins, 74 catheter tips were incubated in thioglycollate media for up to ten days. Fifteen (20.3%) of the catheters were found to be culture-positive. Propionibacterium acnes was isolated from seven, Staphylococcus epidermidis from six, and Staphylococcus haemolyticus and Staphylococcus hominis from one each, all common skin organisms associated with infection of implants. An increase in documentation of bacterial contamination resulted from incubating greater than 72 hours; this allowed the slower-replicating Propionibacterium acnes to grow to detectable numbers. Because of these findings and those of others, attention is focused on the peripheral vein conduit as a potential source for hematogenous seeding of implants with bacterial cells. Changing peripheral catheters within 24 hours is recommended to reduce the constant risk of occult bacteremia. PMID- 2323140 TI - Colonic pseudoobstruction associated with patient-controlled analgesia after total joint arthroplasty. AB - Patient-controlled analgesia (PCA) is a concept that permits patients to administer a prescribed dose of narcotic to themselves when they experience pain. Six patients developed colonic pseudoobstruction after the use of morphine sulfate administered via a PCA infuser. Early recognition and prompt treatment make this a transient, reversible illness. Treatment includes discontinuing the use of the PCA morphine, eliminating oral intake, ensuring adequate hydration and electrolyte balance, placing a nasogastric tube, rolling the patient, and closely observing for signs and symptoms of worsening colonic distention and possible rupture. PMID- 2323141 TI - Optimization and comparison of three vacuum mixing systems for porosity reduction of Simplex P cement. AB - Simplex P bone cement was prepared in three commercially available vacuum mixing systems, the Enhancement Mixer, the Mixevac II High Vacuum System, and the Mitab Vacuum System, to determine the improvement in fatigue strength associated with porosity reduction of the cement in all three systems. The results of the fatigue tests of vacuum-mixed Simplex P were also compared to the fatigue strength of Simplex P prepared by centrifugation of the cement immediately after mixing. Vacuum mixing one pack of Simplex P per syringe in all three systems was not effective in complete removal of all the large voids from the cement. Fatigue failure occurred very early in those specimens containing the large voids. There was no significant difference in fatigue life between one pack of cement per syringe mixed under vacuum in the three systems and the control cement (no vacuum, uncentrifuged). Vacuum mixing two packs of cement per syringe was more effective than one pack per syringe, and all three systems significantly increased the cycles to failure of Simplex P over the control cement. However, the Enhancement and Mitab vacuum mixing systems still produced some very weak specimens in fatigue. Two packs of cement per syringe prepared in the Mixevac II vacuum mixing system were significantly stronger in fatigue than two packs mixed in either the Enhancement or Mitab vacuum system. The Mixevac II vacuum mixing system was the most effective technique of the three vacuum mixing systems tested. Centrifugation of one or two packs of Simplex P per syringe produced a more uniform cement that was free of large voids and thus eliminated the very weak specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323142 TI - Idiopathic meralgia paresthetica. AB - Idiopathic meralgia paresthetica was treated surgically in 14 men and 11 women, the latter group were a decade older on average. Treatment was unsatisfactory if symptoms had been present for longer than 18 months. Reexploration of the nerve was not therapeutic in those cases in which the initial decompression provided no relief. The usual course of the lateral femoral cutaneous nerve is deep to the lateral end of the inguinal ligament but superficial to the sartorius muscle. However, the nerve may overlie the anterior iliac wing or pass between two slips of the inguinal ligament and may also be compressed if it passes deep to or through the sartorius muscle. PMID- 2323143 TI - Demonstration of blood-vessellike structures in cartilaginous callus by antilaminin and antiheparin sulfate proteoglycan antibodies. AB - The vascularization of the callus of experimental nonfixated tibia fractures in rat was investigated with antibodies against two basement-membrane macromolecules, i.e., laminin and the heparin sulfate, low-buoyant-density proteoglycan. The purpose of the investigation was to study the relationship between the appearance of blood vessels and the development of cartilaginous callus. The ages of the callus were three, five, eight, and 11 days after the fracture, that is, from before the cartilage was demonstrable on Day 5 until the enchondral bone formation started on Day 11. The abundant blood vessels in the differentiating granulation tissue, in the periosteal callus, and in the cortical bone itself were stained, as were the endomysia of the surrounding myofibrils. During the whole course, the cartilaginous callus also contained vessellike structures stained by the antibodies. These structures are apparently nonfunctioning vessels. Also, some of the chondrocytes were stained by antilaminin. This study implies that cartilage is not formed as a result of insufficient blood supply, but rather as a natural link in a predetermined course of the migrating mesenchymal cells. PMID- 2323144 TI - The relationship of the glenohumeral joint capsule to the rotator cuff. AB - The glenohumeral joint capsules of 23 shoulders in which the rotator cuff was not torn were studied by gross dissection and histologic methods. The cuff tendons were resected, leaving the intact capsule attached to the bones. This dissection method provided a unique overview of the capsule in situ and allowed the areas of cuff tendon and muscle attachment to be mapped. The capsule was found to be a continuous cylinder between humerus and glenoid. On approximately one-third of the capsule (the portion adjacent to the humeral tuberosities), tight insertions of cuff tendons were noted. The superior segment between subscapularis and supraspinatus contained the coracohumeral ligament. This segment appeared to reinforce the cuff through a transversely oriented band similar to the glenohumeral ligaments. PMID- 2323146 TI - Protest the continuing common usage of the term osteoarthritis. PMID- 2323145 TI - Fat embolism syndrome complicating intraarterial chemotherapy with cis-platinum. AB - A 19-year-old man with telangiectatic osteosarcoma of the left proximal femur was started on a course of neoadjuvant chemotherapy consisting of intraarterial administration of cis-platinum. Within 72 hours of receiving the first intraarterial dose, the patient developed signs and symptoms of fat embolism syndrome (FES). A physical examination revealed cyanosis, tachycardia, and seizure activity. Laboratory studies demonstrated a pO2 of less than 65 mmHg, lipuria, and a drop in hematocrit of three percentage points. There was no clinical or roentgenographic evidence of pathologic fracture. Tumor necrosis secondary to intraarterial cis-platinum therapy in this patient with osteosarcoma may have caused a sudden release of free fatty acids and embolization of fat macroglobules that precipitated this episode of FES. FES in association with the intraarterial administration of cis-platinum seems not to have been previously reported. PMID- 2323147 TI - The microvascular pattern of the supraspinatus tendon. AB - The vascular pattern of the supraspinatus tendon was studied in 18 human anatomic specimens. The ages of the specimens ranged from 26 to 84 years. Selective vascular injection with a silicon-rubber compound allowed visualization of the vascular bed of the rotator cuff and humeral head. The presence of a hypovascular or critical zone close to the insertion of the supraspinatus tendon into the humeral head was confirmed. However, only a uniformly sparse vascular distribution was found at the articular side, as opposed to the well-vascularized bursal side. This was also confirmed with histologic sections of the tendon. The poor vascularity of the tendon in this area could be a significant factor in the pathogenesis of degenerative rotator cuff tears. PMID- 2323148 TI - Acromial enthesopathy and rotator cuff tear. A radiologic and histologic postmortem investigation of the coracoacromial arch. AB - Changes of the coracoacromial ligament (CAL) at its insertion into the undersurface of the acromion were studied radiologically and histologically in 76 autopsy specimens. Two changes were noted: (1) a downward, bony projection of the acromion, an anatomic variant limited to the area covered by the CAL, which might reduce the height of the subacromial compartment, and (2) a thickened layer of fibrocartilage, constituting a potential cause for narrowing of the subacromial space. The former might act as a predisposing factor for the impingement syndrome, whereas the latter could develop in response to pressure from constituents of the subacromial compartment. The acromial spur was a result of enchondral bone formation. A possible correlation between these changes and rotator cuff tears was investigated. The incidence and severity of cuff tears increased with age. However, there was no correlation between aging and degenerative changes of the undersurface of the acromion, except possibly in very advanced cases. Rotator cuff tears are unlikely to be initiated by impingement; rather, they develop as an intrinsic degenerative tendinopathy. PMID- 2323149 TI - The ultrastructure of the coracoacromial ligament in patients with chronic impingement syndrome. AB - In an ultrastructural study of the cells and matrix of the coracoacromial ligament (CAL) in 11 patients with impingement syndrome (IS), the cells appeared variegated, in contrast to those in normal CALs. Many showed degenerative changes such as lipid inclusions in the cytoplasms or swelling of cytoplasmic organelles, especially in the vicinity of fibrin exudate where the collagenous matrix disappeared. However, some cells had increased cytoplasmic organelles, including an elaborate Golgi apparatus, indicating enhanced synthetic activity. The matrix, instead of consisting of packed collagenous fibers of fairly uniform diameter as seen in the normal CAL, contained collagen fibers of varying diameters and microfibrils. The ultrastructural features of both the cells and the matrix were suggestive of chronic effects of strain on the ligament. In patients with chronic IS, the CAL has been implicated as the likely cause of impingement when no significant bony or articular abnormality exists. This was not substantiated by the present findings. The changes in the CAL in IS are possibly secondary, and are probably induced by alterations in soft-tissue structures of the subacromial compartment. PMID- 2323150 TI - Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections. AB - Histologic sections from 12 en bloc surgical specimens were studied in order to clarify the pathogenesis of bursal-side rotator cuff tears (BSRCTs). The specimens consisted of the bony insertion, the partially torn area, and the musculotendinous junction of the supraspinatus tendon. There were eight men and four women, with an average age of 48.7 years. Trauma was noted in three instances. All patients exhibited clinical evidence of subacromial impingement, which was confirmed at surgery. Histologic sections were stained with azan or hematoxylin and eosin. All the tears developed from within 1 cm of the insertion. The depth of the tears varied from a superficial flap to a nearly full-thickness tear. Microscopically, the sections demonstrated several abnormalities in addition to degeneration. At the site of insertion and in the distal stump, local disruptions of the normal four layers of enthesis and areas of hypervascularity were observed in all sections. The proximal stumps were rounded, retracted, and avascular, with abundant chondrocytes. No active repair was noted in the proximal stumps. The pathogenesis of BSRCTs appears to be related to: (1) a combination of aging and precarious vascularity of the tendon, (2) repetitive movements of the arm at above-horizontal levels, (3) injury, and (4) especially subacromial-tendon impingement. PMID- 2323151 TI - Classification of rotator cuff lesions. AB - Among various studies reporting the outcome of surgical repairs of rotator cuff tears, comparisons are very difficult because of the absence of a classification system. A proposed classification system takes into account the extent of the tear, its topography in the sagittal and frontal planes, the trophic quality of the muscle, and the integrity of the long head of the biceps. The new classification system exploits the advances in diagnostic imaging and is useful in the assessment of nonoperatively treated patients. PMID- 2323152 TI - Roentgenographic findings in massive rotator cuff tears. A long-term observation. AB - It is difficult to determine the size and localization of rotator cuff tears preoperatively. But with the special arthrographic technique, a diagnosis with about 80% accuracy was possible in 65 surgically confirmed rotator cuff tears. With this technique, 22 massive cuff tears were found in conservatively treated patients. In these patients, the plain roentgenograms obtained at the initial examination were also analyzed. The roentgenographic findings included narrowing of the acromiohumeral interval and degenerative changes of the humeral head, the tuberosities, the acromion, the acromioclavicular joint, and the glenohumeral joint. Based on these data, five roentgenographic grades of massive cuff tears were identified. Of seven patients with massive tears, which had been treated conservatively and followed for more than eight years, the roentgenographic grades advanced in five. One shoulder progressed to cuff-tear arthropathy. Based on these observations, it is proposed that the following pathogenetic mechanisms are responsible for the progressive roentgenographic changes: (1) arm elevation in activities of daily living, (2) rupture of the long head of biceps tendon, (3) the abnormal fulcrum of the humeral head against the acromion and the coracoacromial ligament, and (4) the weakness of external rotation. A massive cuff tear will progress to cuff-tear arthropathy, with each step of progression accompanied by characteristic roentgenographic changes. PMID- 2323153 TI - Clinical pharmacokinetics in the drug regulatory process. PMID- 2323154 TI - Clinical pharmacokinetics after repeated intrapleural bupivacaine administration. AB - Patients (n = 14) who underwent thoracotomy during surgery of the oesophagus for cancer received an initial intrapleural dose of 10 ml bupivacaine hydrochloride 2.5 mg/ml followed by repeated administration every 8 hours from the first to the fourth postoperative day. The mean (+/- SD) peak plasma drug concentration (Cmax) [352 +/- 120 micrograms/L], time to peak (tmax) [0.83 +/- 0.51 h], and first order absorption rate constant (ka) [5.46 +/- 4.95 h-1] after the twelfth dose were significantly different from the Cmax (206 +/- 81 micrograms/L), tmax (1.8 +/- 1.2h), and ka (1.8 +/- 1.47 h-1) determined after the first dose. Half-life (3.5 +/- 2.2h) and mean concentration (204 +/- 105 micrograms/L) were not significantly different on the fourth day from those on the first (4.1 +/- 2.6h and 142 +/- 71 micrograms/L, respectively). No sharp peak corresponding to systemic toxicity and no accumulation could be expected with these low doses, administered at short intervals and providing good pain relief in this surgical series. PMID- 2323155 TI - Quantification of the EEG effect of midazolam by aperiodic analysis in volunteers. Pharmacokinetic/pharmacodynamic modelling. AB - The effects of midazolam on the EEG were related to plasma midazolam concentrations in 8 healthy male volunteers in order to develop a pharmacokinetic pharmacodynamic model. The EEG parameters were derived by aperiodic analysis. The EEG was recorded between Fp1-M1 and Fp2-M2. Following a 15-minute baseline EEG registration, midazolam 15 mg was given intravenously over 5 minutes. Venous blood samples were taken until 8 hours after the start of the infusion. Within 2 to 4 minutes of starting the infusion all subjects became asleep, with loss of eyelid reflex. The most obvious EEG changes, in the beta frequency range (12 to 30 Hz), were observed within 2 minutes of the start of drug administration. Seven subjects awoke 60 to 70 minutes after the start of the infusion and 1 awoke after 45 minutes. The EEG parameter that best characterised the effect of midazolam was the total number of waves per second in the frequency range 12 to 30 Hz (TNW12 30). This was used as the effect parameter in the pharmacokinetic-pharmacodynamic modelling. The plasma concentration-time data were characterised by a triexponential function for all subjects. To allow for a possible delay between plasma midazolam concentration and EEG effect, a hypothetical effect compartment was included in the pharmacokinetic-pharmacodynamic model. A sigmoid maximum effect (Emax) model was used to characterise the effect compartment midazolam concentration-TNW12-30 data. The plasma drug concentration corresponding to half the maximum increase in TNW12-30 (EC50) was 290 +/- 98 micrograms/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323156 TI - Chlorpromazine disposition in relation to age in children. AB - The pharmacokinetics of chlorpromazine after intravenous infusion were studied in 25 children. The pharmacokinetic parameters studied are markedly different from those reported for adults. A clear relationship was demonstrated between age, serum terminal half-life (r = 0.75) and systemic clearance (r = -0.43). It appears that the pharmacokinetics of chlorpromazine are more rapid in children than in adults. PMID- 2323157 TI - Carotenoid composition, concentrations, and relationships in various human organs. AB - The carotenoid content of 10 different organs obtained at autopsy from 16 humans was determined using a high-performance liquid chromatography assay. The same qualitative pattern of carotenoids found in serum was found for all the tissues, although there were important quantitative differences in the different carotenoids between organs. The median levels of zeaxanthins, lycopene and beta carotene varied disproportionately between organs; similar levels of one carotenoid for two organs would not predict similar levels of another carotenoid for the same organs. Similarly, there was not a consistent relationship between all the carotenoids for a given organ. The uneven but wide tissue distribution of most dietary carotenoids may indicate an active biological role for these compounds. PMID- 2323158 TI - Butyrylcholinesterase fluctuation in male albino rats with intracerebroventricular injection of gamma aminobutyric acid, muscimol, and picrotoxin. AB - The effects of intracerebroventricular injection of gamma-Aminobutyric acid, muscimol, or picrotoxin have been studied on butyrylcholinesterase (BuChE) activities in the serum and several hypothalamic nuclei using biochemical, histochemical, and cytophotometric techniques, respectively. The blood samples were withdrawn from indwelling catheters in jugular vein 1, 15, 30, 45, 60, 90, and 120 min after injection of the drugs. Biochemical estimations demonstrated a significant inhibition of BuChE after GABA and muscimol injections, whereas a pronounced stimulation of BuChE was observed after injection of picrotoxin. The peak changes were observed within 30 min of drug injection. Cytophotometric studies have appeared to dovetail the biochemical findings. Only a marginal decrease was observed after injection of GABA in all nuclei, while muscimol induced a very conspicuous decrease of BuChE. On the contrary, intracerebroventricularly administered picrotoxin markedly increased the levels of BuChE activity. Thus it could be concluded that probably GABA and muscimol along with picrotoxin appear to alter BuChE. PMID- 2323159 TI - Electrolyte transport in rat colon: comparative effects of intestinal resections and bypass. AB - In the present study the influence of different types of intestinal resection (50% distal and 50% proximal small bowel resection) and bypass (50% jejunoileal bypass) upon water and electrolyte (Na and K) colonic transport was examined. Four weeks after resections and bypasses no significant changes in wet and dry tissue weights, serum sodium and potassium values were found in comparison to sham-operated controls. In vivo net absorption of sodium, measured in micromoles of 22Na+ which disappeared from the medium during a determined period (15, 30, 45 and 60 min), in sham-operated animals, showed a gradual increase with the increase in the perfusion time, rising from 144 +/- 20 mumol at 15 min of perfusion to 425 +/- 28 mumol at 60 min. One month after the resection, Na absorption, expressed as total absorption and as micromoles per square centimeter, was not significantly modified in animals distally and proximally resected, but did significantly increase in bypassed rats with respect to sham operated animals. When the results were calculated taking into account the tissue wet weight, the values of the resected rats continued to show no modifications; however, there was a compensation in the bypassed rats. These data demonstrate that the increase in the absorptive capacity of the colon in bypassed rats is due to morphological changes, which could originate from the trophic influence of enteroglucagon or from the effect of the secretions which flowed directly into the colon from the blind loop, an action which does not occur in resected rats. The effects of resection and bypass upon K+ colonic secretion showed no significant differences among the groups studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323160 TI - The application of clinical guidelines for skull radiography in the Accident and Emergency department: theory and practice. AB - Clinical guidelines for the selection of patients with head injuries for skull radiography, based on those formulated by the Royal College of Radiologists, were introduced into the Accident and Emergency department at the Manchester Royal Infirmary. Before the guidelines were implemented 94 skull X-rays were obtained per 1000 new casualty attenders. After implementation the rate of skull radiography initially fell by 40%, but thereafter slowly increased so that 12 months later it had returned to the pre-implementation level. During the first and second 6 months of the study reductions of 37% and 17%, respectively, were achieved. Although the overall annual reduction was only 27% an estimated saving of almost 10,000 pounds was made. Although clinical guidelines for skull radiography can reduce the number of skull radiographs without detriment to the care of the head-injured patient, their constant use is difficult to sustain. The application of clinical guidelines needs regular monitoring. Referring clinicians and radiologists need to be strongly motivated if such guidelines are to find a useful place in clinical management. PMID- 2323161 TI - Imaging cholesteatoma. AB - Acquired cholesteatoma of the middle ear is usually diagnosed by otoscopy and treated by exploratory surgery. The role of imaging for such cases is as controversial now as it was 10 years ago, despite significant improvements in spatial and contrast resolution resulting from computerised sectional imaging. We examined 16 cases of straightforward acquired middle ear cholesteatomas with MR as well as high resolution CT scanning to assess the possibilities for tissue characterisation. Cases of the much rarer but more important congenital cholesteatoma of the petrous pyramid with a normal eardrum were also diagnosed by CT and MRI. Magnetic resonance will distinguish cholesteatoma from granulation tissue, fluid and the cholesterol granuloma in the middle ear but this differentiation is of no practical value. An expansile lesion in the petrous apex is most likely to be a cholesteatoma or cholesterol granuloma and is well shown but not differentiated by CT. The two types have quite different characteristics on MR protocols and this is important for planning surgical procedures. PMID- 2323162 TI - Radiography of the paranasal sinuses--one or three views? AB - A prospective study of 100 adult patients undergoing paranasal sinus radiography was performed. Two experienced radiologists independently assessed a single occipitomental view and, at a later date, the traditional three projections, i.e. occipitomental, occipitofrontal and lateral. There was 99% intra-observer agreement between the diagnosis on a single projection compared with all three films. In five cases, the frontal sinuses were difficult to assess mainly due to poor radiography, and in defined circumstances additional views may be required occasionally. We conclude that with greater attention to radiographic technique the occipitomental view alone is sufficient for diagnostic purposes. PMID- 2323163 TI - Radiological changes in the gastrointestinal and genitourinary tract following radiotherapy for carcinoma of the cervix. AB - The radiological examinations of 67 patients who had previous radiotherapy for carcinoma of the cervix uteri were reviewed. All had evidence of radiation damage proven surgically or histologically. Patients with known recurrent or metastatic disease were excluded. The commonest abnormalities (36 patients) were in the urinary tract, where hydronephrosis due to distal ureteric stricture was the most frequent finding. Changes observed in the bladder included mural thickening, mucosal irregularity, focal ulceration and reduction in size. Thirty-one patients had abnormalities of their large bowel. The majority of these had strictures of the recto-sigmoid which showed a smooth mucosa, fine surface ulceration, focal ulceration or a 'cobble-stone' appearance. Lesions observed in the small bowel included fixity of bowel loops, thickening of the wall, coarsening of the mucosal pattern and strictures. Two new features are described; the development of high ureteric strictures and the presence of a stricture within a large bowel stenosis. These findings are significant since they show the variation in appearance which can be produced by radiotherapy damage. The differentiation of these changes from recurrent malignancy can be difficult and the differential diagnosis is discussed. PMID- 2323164 TI - Rectosigmoid obstruction caused by ovarian cancer. AB - Out of a total of 379 patients with ovarian carcinoma a rectosigmoid stenosis was detected in 44 (12%). A barium enema was available in 27 cases, which revealed a severe stenosis (less than 1/2 lumen open) in 23, with an average length of 17 cm (5-40 cm). Five characteristic types of stenosis were found: solitary stenosis (n = 6), large spherical impression (n = 6), multiple stenoses (n = 4), long narrow tract (n = 6) and a total obstruction (n = 5). Desmoplastic reaction with tethering and/or parallel folds (n = 16) or fixation and/or angulation (n = 18) were frequently found, but tumour invasion was rare (n = 3). A sigmoid resection (n = 1) or colostomy (n = 3) was seldom needed, due to beneficial response to combined therapy. PMID- 2323165 TI - Biliary complications following orthotopic liver transplantation. AB - The gall-bladder conduit anastomosis (choledocho-cholecysto-choledochostomy) has been the most frequently used technique for the biliary tract anastomosis in the Cambridge/King's College Hospital joint liver transplantation programme since 1976. Cholangiograms and interventional biliary procedures performed over a 3 year period were reviewed retrospectively. Seventy-six of 148 patients managed post-operatively at King's College Hospital were studied (79 transplants). Cholangiograms were abnormal in 63 (80%) transplants with biliary strictures; inspissated bile formation, bile leak and T-tube malposition occurring in 50, 23, 14 and three transplants respectively. Anastomotic strictures occurred most frequently, predominantly at the proximal anastomosis, and the presence of inspissated bile and the T-tube in relation to these contributed towards subsequent biliary obstruction. Non-anastomotic strictures in the donor biliary tract were associated with a high position of the T-tube tip at or above the liver hilum. Saline irrigation of the bile ducts for inspissated bile or its removal via the endoscope were effective measures in the management of biliary obstruction but percutaneous balloon dilatation and endoscopic stent insertion for biliary strictures were found to have a limited role. PMID- 2323166 TI - Powered cutting needle biopsy of the pleura and chest wall. AB - Over a 24 month period, 35 patients seen consecutively with a pleural or chest wall mass had a percutaneous biopsy using an 18 gauge cutting needle operated by a specially designed, hand held, spring loaded trigger system (Biopty TM, Biopsy instrument, Radiplast A.B. Sweden). Biopsies were performed under local anaesthesia with ultrasound, fluoroscopic, or computed tomography guidance, depending on the site and nature of the lesion. An excellent specimen, consisting of a core of tissue, was consistently obtained and a specific histological diagnosis was possible in 30 patients (28 malignant lesions and two benign lesions). In two patients there was an unequivocal diagnosis of malignancy but the tumour was too necrotic to allow a cell type to be established. In three patients the specimen consisted predominantly of dense fibrous tissue. One of these was a presumed false negative result for malignancy; the other two are presumed true negative results. There were no complications of the procedure. PMID- 2323167 TI - CT features of histiocytic medullary reticulosis. AB - Five cases of histiocytic medullary reticulosis (HMR) are presented and the computed tomographic (CT) findings described. All patients were young adults in their early twenties with fever, malaise and weight loss as their chief complaints. Survival was less than 5 months in all cases. The CT findings were hepatosplenomegaly (5), abdominal lymphadenopathy (5) and bilateral renal enlargement (2). Patchy low attenuation areas in the liver (2), wedge shaped splenic infarcts (2) and focal low attenuation areas in the kidneys (1) were also noted. Ascites (3) and pleural effusion (3) were associated findings. PMID- 2323168 TI - Portal venous collateral drainage in IVC obstruction. AB - Collateral venous drainage via the portal venous system has been demonstrated in three patients with testicular teratoma and IVC obstruction using contrast venography and enhanced computed tomography (CT). The use of CT in assessing the extent of the collateral circulation in IVC obstruction together with implications for surgical management are discussed. PMID- 2323169 TI - Magnetic resonance imaging with gadolinium-DTPA enhancement in the differentiation of benign from neoplastic cord cavitation. AB - A patient with an extensive spinal cord glioma is presented. The lumbar mass and cervical cavity associated with the tumour were demonstrated by myelography and computed tomography. Magnetic resonance imaging provided greater detail than these conventional imaging modalities without exposure to ionising radiation and was of considerable additional value in the planning of surgery. PMID- 2323170 TI - Myocardial bridging of the coronary arteries. PMID- 2323171 TI - Benign breast change. PMID- 2323172 TI - A device to measure head-turn reflex in the distribution test used for infant hearing assessment. AB - A device was constructed to measure infant head rotation during orienting reflexes to sound stimuli. An experiment was devised to compare the device output with visual observation of the infant. Four stimulus and four no-stimulus control trials were presented randomly to each of 24 infants. Fourteen scorers examined a hardcopy record of the device output followed by a video of the same tests for the presence of head-turn responses to the sound stimuli. The results of this study have shown that it is possible to construct a device to detect head-turn reflexes from young children. However, the success rate in detecting head-turns was inferior to visual scoring of the video of the child's behavior. This was due to the lack of precision of the device. An improved device may overcome this problem and could provide the basis for a useful addition to distraction testing. PMID- 2323173 TI - A comparison of three indices of relative hepatic perfusion derived from dynamic liver scintigraphy. AB - Data from dynamic radiocolloid liver scintigraphy (DLS) have been analysed to calculate three indices of relative arterial to total hepatic perfusion. Ninety subjects have been studied, comprising 21 normals, 62 patients with metastatic liver disease and 7 patients with cirrhosis. Correlation coefficients above 0.81 were found in all patient groups between an index based on rates of liver uptake (the hepatic perfusion index, HPI) and a method based on quantitative liver uptake (the mesenteric fraction, MF). A further method employing the spleen to model arterial inflow (hepatic arterial ratio, HAR) had less agreement with both HPI and MF, with correlation coefficients below 0.76. Posterior images have previously been used to calculate HAR, and greater errors are expected in HAR from the anterior images acquired in this study. Receiver operating characteristic analysis showed that the diagnostic performance of HPI and MF indices in metastatic disease were not significantly different. For anterior image data analysis both HPI and MF were superior to HAR. PMID- 2323174 TI - An evaluation of radiofrequency exposure from therapeutic diathermy equipment in the light of current recommendations. AB - Shortwave and microwave diathermy equipment use by physiotherapy departments in Grampian Region has been studied. Stray electric and magnetic fields close to equipment have been measured and compared with exposure levels recommended by the INIRC and the NRPB. Fields above the recommended whole body levels extend to 0.5 1.0 m from the electrodes and cables for continuous wave (cw) shortwave equipment, and up to 0.5 m for microwave units and pulsed shortwave models. Operators were exposed to local fields above these values for 2 - 3 min during cw shortwave treatments, but rarely exceeded the recommended exposure. However, short localised exposures to high fields, which can occur if the operator moves close to the electrodes or cables, could exceed these limits. Physiotherapists are advised to remain at a distance of at least 1 m during cw treatments, and not to approach within 0.5 m of the electrodes and cables even for a short period. PMID- 2323175 TI - Periotest--a dynamic procedure for the diagnosis of the human periodontium. AB - The Periotest is a new instrument for the diagnosis of periodontal diseases. The Periotest value depends to some extent on tooth mobility, but mainly on the damping characteristics of the periodontium. The Periotest measures the reaction to a reproducible impact applied to the tooth crown. PMID- 2323176 TI - Triple photon absorptiometry cannot correct for fat inhomogeneities in lumbar spine bone mineral measurements. AB - In vivo fat inhomogeneities can cause significant errors in measurements of lumbar spine mineral mass using dual photon absorptiometry. Extension to a triple photon technique to correct for the presence of fat is not possible because of the unacceptable increase of about a factor of 3,000 required in the radiation dose to yield sufficient transmitted photons for adequate precision. PMID- 2323177 TI - Accuracy of infusion pumps at low flow rates. PMID- 2323178 TI - Practical aspects of automated performance checking of infusion equipment. PMID- 2323179 TI - Drug-induced pulmonary disease. PMID- 2323180 TI - Duck lymphocytes--III. Transformation responses to some common mitogens. AB - The lymphocyte transformation (LT) test was performed using duck blood lymphocytes stimulated with phytohaemagglutinin (PHA), concanavalin A (Con A), lentil lectin (LC), Roman snail lectin (HP), peanut agglutinin (PNA), Bandeiraea simplicifolia seed lectin (BSS), wheat germ agglutinin (WGA), horseshoe crab lectin (HSC), pokeweed mitogen (PWM) and E. coli lipopolysaccharide (LPS). Cells were cultured in microtitre trays, at 41.6 degrees C, 8 x 10(5) cells in 200 microliters medium (= 4 x 10(6) cells/ml) supplemented with 10% pooled duck serum. Mitogens were added at final concentrations of 0.1-100 micrograms/ml and triplicate cultures at each concentration were harvested daily for scintillation counting 6 hr after addition of 1 microCi [3H]thymidine. Three patterns of response were observed. The responses to Con A, LC, HP and HSC were greatest at high mitogen concentrations (40-100 micrograms/ml) throughout the 7 days of culture. With PHA, PNA, WGA and LPS maximum stimulation was obtained at 3-5 days, at which time the cells were responding to lower concentrations of mitogen than were required at other times during the experiment. The response to BSS and PWM showed increasing sensitivity to lower concentrations of mitogen during the first 3 days of culture and then stimulated most strongly at 2-10 micrograms/ml in cultures harvested after 4-7 days. Cells from two ducks were cultured for 3 and 5 days with selected concentrations of these mitogens; the results confirmed the variation in response to different mitogens. It is possible that these patterns of response are the outcome of stimulating different populations of duck lymphocytes. PMID- 2323181 TI - Studies on the interactions of two different serotypes of Actinobacillus pleuropneumoniae. AB - In vitro and in vivo interactions of various field strains of Actinobacillus pleuropneumoniae of serotypes 1, 2, 5 and 7 were studied. There was no influence of one serotype over the other when strains belonging to two serotypes were cultivated together in vitro. In vivo interactions showed predominance of serotype 1 over other serotypes when a strain of serotype 1 was inoculated together with a strain of serotype 2 or 5 in mice. Serotype 1 strain remained predominant irrespective of whether it was inoculated before or after the inoculation of serotype 2 strain. The mortality caused by the inoculation of two strains was higher than the mortality caused by a single strain. Early mortality was observed on inoculation of strains of serotype 2, 5 or 7 along with a strain of serotype 1. Both serotypes could be detected in the blood on cultural examination of mice infected with mixed serotypes. PMID- 2323182 TI - A survey for haemagglutination-inhibiting antibody to West Nile virus in human and animal sera in Nigeria. AB - A survey for West Nile Virus (WNV) haemagglutination-inhibition (HI) antibody was carried out in humans and domestic animals. Human sera were collected from Ibadan, while the animal sera were collected from both Ibadan and Maiduguri. Out of 304 human sera tested, 123 were positive (40%). There was a higher prevalence of HI antibody in adults than children. Sex distribution of positive sera showed that 37% of males and 43% of females had WNV HI antibody. There was no significant difference in the prevalence of HI antibody in both sexes. On the 123 WNV HI positive sera tested, 104 (85%) and 78 (75%) had yellow fever and Potiskum HI antibody respectively. Monotypic WNV virus reactions were frequently found in children while polytypic reactions were frequently found in adults. A total of 200 animal sera were examined, 50 camels, 50 goats, 49 cattle and 51 sheep. The highest prevalence of HI antibody was found in camels (26%), followed by sheep (20%). Percentage of positive sera in other species were: goat (18%) and cattle (6%). Of the 35 WNV HI positive animal sera, 26 and 20% reacted with Yellow fever and Potiskum virus antigens respectively. PMID- 2323183 TI - Analysis of the binding of human C3b to glycoproteins on rabbit and sheep erythrocytes. AB - To investigate the possibility that activation of the human alternative pathway of complement is influenced by cellular constituents that interact with C3b, the membrane proteins on rabbit and sheep erythrocytes that are associated with cell bound human C3b have been analyzed. For both types of erythrocytes, activated C3b bound in a diffuse pattern via hydroxylamine-sensitive ester bonds. By using a homobifunctional crosslinker, a membrane component that has an apparent Mr of 35 kDa was shown to be noncovalently associated with C3b on sheep erythrocytes, but rabbit erythrocytes lacked a predominant C3b-associated protein. These studies suggest that regulation of human alternative pathway activity may be influenced by membrane glycoproteins that interact with cell-bound C3b. PMID- 2323184 TI - Specificities of monoclonal antibodies against the complement C3d split product. AB - The only specific method at present for the quantification of the complement split product C3d, the double-decker rocket immunoelectrophoretic assay, is work intensive and expensive. We investigated the possibilities for developing an ELISA for the direct quantification of C3d in plasma. Available antibodies were examined for their specificity for C3 and its degradation products by the PAGE immunoblotting method. None of the antibodies were specific for C3d, as cross reactivities against C3 and/or C3b and C3bi were demonstrable. PMID- 2323185 TI - Purification of C8 and C9 from rat serum. AB - A procedure based on modifications of published methods for human proteins for the isolation of rat C8 and C9 from one batch of serum is described. The procedure allows the rapid, large-scale isolation of pure and haemolytically active proteins. Rat C9 had a slightly higher molecular weight than human C9 on SDS-PAGE and similar isoelectric point. Rat C8 differed from human C8 in the molecular weight of the gamma chain (23,000 and 21,000 kD respectively), and on isoelectric focusing (pI rat C8: 6.5-6.9; pI human C8: 7.4-7.9). PMID- 2323186 TI - Contact allergy to Bronopol. AB - A total of 8149 patients were patch tested with the preservative Bronopol in 7 European contact clinics. The majority of patients (6507) were investigated in London. Reactivity was low, with a total of 10 irritant (0.12%) and 38 allergic reactions (0.47%). In only 17 cases (0.21%) was the patch test reaction to Bronopol considered to be of current or past clinical relevance. Concomitant sensitization to formaldehyde was present in about 1/3 of patients. Based on these figures, the present sensitization rate to Bronopol in Europe seems to be quite low, which may be related to its less frequent use as a preservative in cosmetics and medicaments in comparison to parabens or isothiazolinones. PMID- 2323187 TI - Cross-reaction in allergic contact dermatitis from alpha-methylene-gamma butyrolactones: importance of the cis or trans ring junction. AB - Cross-reaction in allergic contact dermatitis (ACD) is a highly stereoselective process. The importance of the cis or trans ring junction in alpha-methylene gamma-butyrolactones in cross-reactivity was investigated by reacting Helenin (mostly a mixture of natural allergenic sesquiterpene lactones alantolactone 1 and isoalantolactone 2, which present a cis ring junction) in guinea pigs sensitized to model allergenic alpha-methylene-gamma-butyrolactones: cis-bicyclic lactone 3 and trans-bicyclic lactone 4. PMID- 2323188 TI - Photoallergic reaction to fluorescein. AB - A photoallergic reaction to fluorescein was demonstrated in a male diabetic by photopatch and photoprovocation tests. Sensitization was acquired by tonometries using a fluorescein-containing local anesthetic, preceding fluorescein angiography for diagnosis of diabetic retinopathy. Histopathological examination of skin lesions induced in both photopatch and photoprovocation tests confirmed the diagnosis of photoallergic reaction to fluorescein. PMID- 2323189 TI - Active sensitization to elecampane by patch testing with a crude plant extract. PMID- 2323190 TI - Contact sensitivity to para-tertiary-butylcatechol in an artificial limb. PMID- 2323191 TI - A general method for photohaptenization. PMID- 2323192 TI - Allergic contact dermatitis from a sulfosuccinate derivative in a hand cleanser. PMID- 2323193 TI - Phytophotodermatitis from Ruta corsica. PMID- 2323194 TI - Changes in penicillin contamination and allergy in factory workers. PMID- 2323195 TI - Contact dermatitis from cyclohexanone-formaldehyde resin (L2 resin) in a hair lacquer spray. PMID- 2323196 TI - An unusual delayed patch test reaction to para-tertiary-butylcatechol. PMID- 2323197 TI - Androgenetic alopecia--is contact dermatitis an accelerating factor? PMID- 2323199 TI - Connubial contact dermatitis from nifuratel. PMID- 2323198 TI - Contact stomatitis due to N,N-dimethyl-para-toluidine. PMID- 2323200 TI - Contact dermatitis due to piperazine in a plastic watch strap. PMID- 2323201 TI - Transepidermal water loss and air convection. PMID- 2323202 TI - Allergic contact dermatitis from fluocortin butylester. PMID- 2323203 TI - Contact sensitization to diazolidinyl urea: report of 3 cases. PMID- 2323204 TI - Allergic contact dermatitis from gardenia fruit. AB - A 41-year-old man, with severe itchy dermatitis on the left leg, had treated a bruise on the left knee with a topical folk remedy called Sokujikoh, which contains about 16% powdered gardenia fruit. After 4 days, an exacerbation of symptoms appeared, with edema, erythema, and vesicles on the treated area. Patch testing indicated sensitivity to the seeds of gardenia fruit and, to a lesser extent, the pericarp (fruit wall). The allergens could be extracted into ethanol and, less readily, into water. PMID- 2323205 TI - An epidemiological study of contact allergy to 5-chloro-3-methyl isothiazolone/3 methyl isothiazolone in Strasbourg. AB - In Strasbourg, the incidence of allergy to the mixture of 5-chloro-3-methyl isothiazolone and 3-methyl isothiazolone (MCI) in 540 patients (313 women and 227 men), routinely tested with this preservative as part of the standard series of allergens, was 1.11%. The frequency was 1.6% in women and 0.44% in men. A total of 6 cases of allergy, 5 in women and 1 in a man, to MCI were detected. In 5 cases out of 6, the patient was shown to have used cosmetic products containing this preservative. Finally, in 5 cases out of 6, the subjects allergic to MCI also tested positively for nickel, while only 15% of the total of 540 subjects tested with MCI had a nickel allergy confirmed by patch tests. PMID- 2323206 TI - Evaluation of a questionnaire for facial skin complaints related to work at visual display units. AB - A questionnaire about facial skin problems was answered by 3745 office employees, with the aim of discovering whether VDU work causes skin disease. From this group, 809 randomly selected persons were examined and interviewed by a dermatologist. There was a relatively good correspondence (87%) between the results from the interviews and the questionnaires, but the questionnaire results corresponded to current status in only 46% of the cases. No important difference was seen between those who were informed and those who were not informed about the purpose of the investigation. There was a relatively wide variation in the correlation between 2 responses to the same questions. In conclusion, the self administered questionnaire seems to give reasonably adequate answers regarding the occurrence of more clear-cut symptoms over a period of time, rather than answers regarding the presence of signs at a particular point in time. However, less marked changes might not be picked up particularly well. PMID- 2323207 TI - Seasonal koilonychia in Ladakh. AB - During a health survey for chest disease in Ladakh, it was noted that women and a few men had marked koilonychia. It caused disfigurement, discomfort and sometimes disturbance of function. It occurred mainly in spring and summer and usually disappeared in winter. It is thought to be due to exposure to cold wet mud while repairing walls and irrigation canals. There was no evidence of iron deficiency. PMID- 2323208 TI - Wood tars allergy, cross-sensitization and coal tar. AB - In a population of 1883 patients tested for allergic contact dermatitis (1985 1988), a prevalence of 5.4% (103 cases) was seen for wood tars (ICDRG allergen, 12% pet.) sensitization. In this group (n = 103), retrospectively, a combined allergy was seen to wood tars and fragrance mix in 43% and to wood tars and balsam of Peru in 31%. A combined allergy to wood tars and coal tar was seen in 19 patients (18.5%): 14 to liquor carbonis detergens (LCD), 8 to lianthral and 3 to both LCD and lianthral. Within the group with wood tars allergy (n = 103), a minority (n = 37) had a history of atopic dermatitis. Comparison of the test results in atopic and non-atopic subgroups (within the group of 103) revealed a higher incidence of combined wood tars-fragrance mix allergy in the atopic group (n = 37). In this group, a lower incidence of combined wood tars-coal tar sensitization was seen in comparison with the non-atopic group (n = 66). The authors believe that combined "wood tars-coal tar" allergy could be the consequence of cross-sensitization rather than due to long-term previous topical treatment with tar derivatives. The high % of cross-allergy between wood tars and fragrance mix emphasizes the role of wood tars as an important indicator allergen in perfume allergy. PMID- 2323209 TI - Contact depigmentation from free para-tertiary-butylphenol in bindi adhesive. AB - 100 consecutive cases of contact depigmentation due to bindi during a period of 11 months were studied. Bindi adhesive material was found to contain 80% para tertiary-butylphenol (PTBP), by thin-layer chromatography, infrared spectrophotometry and high-pressure liquid chromatography. The possibility of hypersensitivity to PTBP was ruled out as none of the 15 patients tested with 2% PTBP and 1% para-tertiary-butylphenol-formaldehyde resin gave any positive reactions. Development of depigmentation could have been due either to individual susceptibility or to constant use for a prolonged period. The area of contact being very small, generalised vitiligo as a result of systemic absorption appeared to be a remote possibility. PMID- 2323210 TI - The infant walker: an unappreciated household hazard. AB - The potential for infant walkers to cause injury to infants was demonstrated by the results of a survey of the practicing pediatricians in the state of Connecticut. There was a significant number of severe injuries reported. In addition, seven cases of infants hospitalized at Bridgeport Hospital because of injuries sustained while using an infant walker are included. The survey indicated adequate knowledge of the apparent danger by the practicing physicians, including discussion during anticipatory guidance. Despite this knowledge and guidance, significant morbidity continues to occur. PMID- 2323211 TI - Gastrointestinal complications of metastatic malignant melanoma. AB - In a retrospective search of over 450 patients with melanoma, 13 were identified as having gastrointestinal metastatic disease. The clinical symptoms are nonspecific. The histology was either superficial spreading or nodular, and the depth of invasion was highly variable. The average survival of patients who underwent surgical treatment for symptomatic gastrointestinal (GI) metastatic disease was 14 months. We conclude that a subset of patients with malignant melanoma will present with symptomatic GI involvement, especially those with primary lesions of Clark Level III or deeper. Operative intervention in this group of symptomatic patients can be safe, and palliation for prolonged periods has been obtained. The authors encourage an aggressive diagnostic and therapeutic approach. PMID- 2323213 TI - The coming push for national health care. PMID- 2323212 TI - Health care coverage needs major surgery. PMID- 2323214 TI - Access to care. PMID- 2323216 TI - More on podiatric and orthopedic surgery. PMID- 2323215 TI - Judge Young and the legal status of the human embryo. PMID- 2323217 TI - The use of the antiprogestin RU486 (mifepristone) as an abortifacient in early pregnancy--clinical and pathological findings; predictive factors for efficacy. AB - RU486, a potent antiprogesterone steroid was administered to 124 women requesting therapeutic abortion. All were less than 49 days from their last menstrual period. Ten of these subjects (Group I) received high doses of RU486 in a decremental dose regimen (400, 300, 200 and 100 mg/day) over 4 successive days and 14 received 50 mg/day for 7 days (Group II). A further 50 subjects (Group III) received 100 mg/day for seven days and the remaining 50 subjects (Group IV) received 450 mg in a single dose. In the first three groups, half the daily dose was given in the morning and the remainder in the evening. Blood was collected before, and on Days 4 and 7 and then once a week after commencing therapy until disappearance of circulating beta HCG. In addition to beta HCG, estradiol-17 beta (E2), progesterone (P), cortisol, and various metabolic and hematological parameters were measured. Plasma RU486 concentrations were also assayed in Group II, III and IV subjects on Day 7 of therapy and in some cases on Days 14 and 21. Ultrasonography was performed in all cases on Day 1 and on Day 14. All the patients bled within five days following RU486 administration, for 1 to 21 days. A complete abortion occurred in 60% in Group I, 50% in Group II, 86% in Group III, and 80% in Group IV. The difference between the last two groups and the first two was significant at p less than 0.01. The non-responders were submitted to a uterine vacuum aspiration. A stepwise discriminant analysis was performed and indicated that the best predictors of the outcome of therapy were beta HCG values and the gestational sac diameter. With these criteria, the prediction was accurate in 86.4% of the cases. The best results were obtained in the cases where the ultrasonic measurement of gestational sac was under 10 mm in diameter and the initial beta HCG values under 15,000 mIU/ml. Among the observed side effects were moderate pelvic cramps (20.9%), nausea (27%), fainting (4.8%); 61.3% of the women complained of fatigue. Heavy bleeding occurred in 15.3% of the women but only one of them required blood transfusion. In the patients with complete abortion, beta HCG values decreased to below 500 mIU/ml by Day 14 (but in 11 cases values fell below 2,000 mIU/ml only by Day 21). Plasma estradiol and progesterone also fell. Cortisol levels increased during therapy especially in subjects of Group I, but returned to basal values after termination of treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2323218 TI - The influence of copper surface area on menstrual blood loss and iron status in women fitted with an IUD. AB - The influence of copper surface area on menstrual blood loss (MBL) was evaluated in 34 healthy women (mean age 36.4 +/- 1.4 yr, range 27-46 yr), who were fitted with a Multiload intrauterine device (IUD) with either 250 mm2 (MLCu-250) or 375 mm2 (MLCu-375) copper wire. MBL prior to IUD insertion was 54.4 +/- 10.3 ml for women subsequently fitted with a MLCu-250 and 56.9 +/- 6.9 ml for women fitted with a MLCu-375. An increase (p less than 0.01) in MBL was recorded 3 months after IUD insertion for both the women fitted with a MLCu-250 (86.4 +/- 10.3 ml) and a MLCu-375 (81.1 +/- 8.3 ml). This increase in MBL remained unchanged throughout the study period of one year. At no point were there any significant differences in MBL or increase in MBL between women fitted with a MLCu-250 or MLCu-375. There were no significant differences in serum ferritin, blood hemoglobin, hematocrit or erythrocyte indices before IUD insertion in the women grouped according to type of IUD, nor were any significant changes recorded in any of these parameters after IUD insertion. Thus, our findings that the increase in copper surface area from 250 mm2 to 375 mm2 had no effect on MBL were also substantiated by the hematological findings. PMID- 2323219 TI - Cervical pathology with intrauterine contraceptive devices--a cyto-colpo pathological study. AB - One-hundred Lippes loop and 100 Cu T-200 intrauterine contraceptive device (IUCD) users, for more than one year, and 200 control non-users were examined clinically, cytologically, colposcopically and histopathologically for associated cervical pathological lesions. Nonspecific infection increased significantly in both Lippes loop and Cu T-200 IUCD users, compared to non-users (P less than 0.05). On the other hand, there was no statistically significant difference in the incidence of total, or individual, specific infections, dyskaryosis or CIN between both groups (P greater than 0.05). Colposcopically, there was a significant increase in inflammatory changes with both Lippes loop and Cu T-200 IUCD, compared to controls (P less than 0.05), but there was no difference in other colposcopic findings (P greater than 0.05). PMID- 2323220 TI - Time-controlled injectable occlusion of the vas deferens. AB - An injectable method of obtaining vas deferens occlusion is presented. The agent used is styrene maleic anhydride (SMA) with dimethyl sulphoxide as the solvent. The special feature of the approach is that after a period of time, spermatozoa passage is spontaneously reestablished. By varying the dose of SMA administered, the interval between injection and restoration of spermatozoa flow can be regulated from as short a period as about 3 months to more than five years. PMID- 2323221 TI - Histological changes in the vas deferens of rats after injection of a new male antifertility agent "SMA" and its reversibility. AB - A new male antifertility agent, styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide (DMSO), was injected into the vas deferens of rats. The morphological changes detected were confined only to the mucosa. After four weeks, the vas deferens lumen was flushed with the solvent DMSO, and the mucosal structures returned to normal. PMID- 2323222 TI - The sting--the annoying IUD thread. PMID- 2323223 TI - Localization of the human A1S9 gene complementing the ts A1S9 mouse L-cell defect in DNA replication and cell cycle progression to Xp11.2----p11.4. AB - The temperature-sensitive ts A1S9 mouse L-cell mutant is defective in an X-linked gene essential for progression of cells through the S phase of the cell division cycle. A single copy fragment derived from the complementing human A1S9 gene was used as a probe to localize the gene on the X chromosome. Southern blot analysis of human x rodent hybrids and in situ hybridization to human metaphase chromosomes allowed the regional assignment of the human A1S9 gene to Xp11.2--- p11.4. PMID- 2323224 TI - Assignment of two rat dihydrofolate (DHFR) genes to chromosomes 2 and 4. AB - A panel of rat x mouse cell hybrids was used in the chromosomal mapping of the rat dihydrofolate reductase (DHFR) gene. It was determined that the probe hybridized to gene sequences on two different chromosomes (Nos. 2 and 4), possibly representing the active gene and a pseudogene. Hybridization of the DHFR probe to DNA from a methotrexate resistant rat cell line revealed that the gene on chromosome 2 was amplified, but not the gene on chromosome 4. This result was taken to suggest that the active DHFR gene is located on rat chromosome 2 and that the sequence on chromosome 4 is a pseudogene. PMID- 2323225 TI - Pachytene pairing and sperm counts in mice with single Robertsonian translocations and monobrachial compounds. AB - Data on testis weights, sperm counts, and synaptonemal complexes are presented for mice carrying the following Robertsonian translocations: Rb(6.15)lAld; Rb(4.6)2Bnr; Rb(4.15)4Rma; Rb(6.15)lAld/Rb(4.6))2Bnr, which is male-sterile; and Rb(6.15)lAld/Rb(4.15)4Rma, which is male-fertile. In RblAld/Rb2Bnr sperm were absent or sparse, whereas the sperm count in RblAld/Rb4Rma was just over 50% of the parental value. The translocated chromosomes appeared as fully paired bivalents in homozygotes, as trivalents in single heterozygotes, and as quadrivalents in compounds. About 20-40% of trivalents had unsynapsed ends. The proportion of quadrivalents with unsynapsed ends was about 85% in the male sterile compound, compared with 75% in the male-fertile compound. The proportion of quadrivalents associated with XY was about 70% in both. Testis weights, but not sperm counts, were found to differ in two of three reciprocal crosses. It is concluded that, in addition to pairing failure and autosome/XY association, the effect of translocations on spermatogenesis is affected by other factors, including genetic background, inbreeding, and perhaps environmental factors. It remains to be elucidated whether pairing failure and XY association are primary or secondary effects. PMID- 2323226 TI - Genetic variation and origin of the most chromosomally polymorphic natural mammalian population. AB - Examination of allozymic variation in a chromosomally highly polymorphic population of Oryzomys documented that the sample consisted of two species, one that was chromosomally monomorphic and the other containing nine centric fusion polymorphisms. The existence of allozymic variation indicates that it is highly improbable that the polymorphic sample was the result of hybridization. These centric fusion polymorphisms appeared to cause little or no negative selection. PMID- 2323227 TI - Common fragile sites in man and three closely related primate species. AB - The expression of common fragile sites was studied in peripheral lymphocytes of man, gorilla, chimpanzee, and orangutan after induction with aphidicolin, methotrexate, or fluorodeoxyuridine. As far as the chromosomal localization is concerned, it appears that many of these sites have been highly conserved during primate evolution. However, differences were found in the relative expression of certain sites. In all four species, mapping of approximately 500 lesions disclosed the most breakage-prone common fragile sites, at which about 90% of all induced aberrations were localized. Comparison of chromosome regions involved in evolutionary changes to fragile sites in the four primate species revealed 30 sites that were located at or close to the same chromosomal band. However, no correlation was found between the relative expression of a certain common fragile site in vitro and a potential involvement of this chromosomal site in evolutionary changes. PMID- 2323229 TI - Hemodynamic compromise associated with air trapping following coronary artery bypass surgery. AB - Cardiovascular collapse due to pulmonary hyperinflation was noted in a patient with chronic obstructive pulmonary disease following median sternotomy for cardiac surgery. Treatment included bronchodilator therapy to reduce airway obstruction, limitation of minute ventilation, and increasing time available for exhalation. High inspiratory flow rates and expiratory retard may be beneficial. PMID- 2323228 TI - Pulmonary malacoplakia and Rhodococcus equi infection in a patient with AIDS. AB - We describe a case of pulmonary malacoplakia and Rhodococcus equi cavitary pneumonia in a patient with AIDS. The relationship between Rhodococcus equi, a rare bacterial human pathogen, and malacoplakia, an unusual type of chronic granulomatous inflammation, is discussed. PMID- 2323230 TI - A case of delayed postoperative cardiac tamponade with unusual echocardiographic findings. AB - Postoperative cardiac tamponade due to localized compression of the atria occurred in a 64-year-old man after aortic valve replacement and repair of an ascending aortic dissection. The clinical findings were subtle and the echocardiographic findings were unusual. Color Doppler flow imaging assisted in making the diagnosis of localized atrial compression. PMID- 2323231 TI - Intrathoracic goiter with hyperthyroidism, tracheal compression, superior vena cava syndrome, and Horner's syndrome. AB - Intrathoracic goiter is an important cause of mediastinal masses. We present a patient with hyperthyroidism, tracheal compression, superior vena cava syndrome (SVCS) and Horner's syndrome due to intrathoracic goiter. To our knowledge, this is the first case in the literature with all of these combined findings. PMID- 2323232 TI - Recurrent pericarditis and dermatitis herpetiformis. Evidence for immune complex deposition in the pericardium. AB - Recurrent pericarditis can be associated with many chronic illnesses. Dermatitis herpetiformis is a chronic papulovesicular eruption which is characterized by granular IgA deposits in the dermal papillary tips and associated with a gluten sensitive enteropathy. We describe the first case of recurrent pericarditis in association with dermatitis herpetiformis. This supposition is supported by exclusion of other possible etiologies and pericardial biopsy which revealed the deposition of IgG, IgA and complement. PMID- 2323233 TI - Acute pulmonary edema in Brucella myocarditis and interstitial pneumonitis. AB - A case of Brucella pneumonitis and myocarditis complicated by acute pulmonary edema is presented. The clinical, laboratory and roentgenographic findings are discussed. PMID- 2323234 TI - Pulmonary edema after freebase cocaine smoking--not due to an adulterant. AB - A case of pulmonary edema following smoking freebase cocaine is described. We did not clearly establish the mechanism, but this case is unique since adulterants and contaminants were excluded unlike all previously reported patients. PMID- 2323235 TI - Intrathoracic lymphadenopathy. A rare manifestation of rheumatoid pulmonary disease. AB - This is the first antemortem report of a patient with long-standing RA and interstitial lung disease who developed reactive mediastinal adenopathy coincident with increases in the activity of his interstitial process. Mediastinal adenopathy was discovered by means of CT of the chest as part of an evaluation of interstitial lung disease. The increasing use of better imaging techniques for this purpose will undoubtedly reveal more patients with this finding. Mediastinal lymphadenopathy complicating rheumatoid lung is clinically relevant; speculation is provided regarding the mechanism of the lymph node enlargement in this setting. PMID- 2323236 TI - Echocardiographic diagnosis of right atrial tamponade. AB - We report the case of a 27-year-old man who developed isolated right atrial tamponade eight weeks following aortic valve replacement. The diagnosis was made by two-dimensional and contrast echocardiography and was subsequently confirmed by cardiac catheterization and surgery. Right atrial tamponade presents a unique conglomeration of clinical, hemodynamic, and echocardiographic features. Constant awareness of this entity is necessary to make a timely diagnosis. PMID- 2323237 TI - Mediastinal pseudocyst associated with chronic pleural effusions. AB - We present a patient who had chronic, bilateral pleural effusions without evidence of parenchymal, retrocardiac or mediastinal masses. A CAT scan of the abdomen and chest revealed the extension of a large abdominal pseudocyst through the diaphragm into the posterior mediastinum. The pseudocyst resolved with conservative management. PMID- 2323238 TI - A case of dirhythmic breathing. AB - We describe a case of dirhythmic breathing in a 60-year-old man after neurosurgery. A large hemangioblastoma was removed from the cerebellum at the level of the fourth ventricle. The spirometric tracings showed two types of respiratory cycles: the rhythm. A was stable with a short inspiratory time; sometimes a second type of respiratory cycle, B, was present or erratically coupled with the A rhythm. It had very small tidal volume and mean inspiratory flow with phasic variations similar to those observed in Cheyne-Stokes breathing pattern. PMID- 2323239 TI - Testing for asthma. PMID- 2323240 TI - Multiple protruding, mobile left ventricular thrombi and risk of embolism after cardioversion. PMID- 2323241 TI - The ventilatory challenge in weaning. PMID- 2323242 TI - The cigarette factor in asbestosis. PMID- 2323243 TI - The National Tuberculosis Training Initiative. PMID- 2323244 TI - Heart failure and the bedside Valsalva maneuver. PMID- 2323245 TI - Acute irritants. More than a nuisance. PMID- 2323246 TI - Immediate echocardiography in the management of acute respiratory exacerbations of cardiopulmonary disease. A prospective study. AB - This prospective study was done to determine whether immediate echocardiography, to implicate or exclude a cardiac basis for breathlessness, can improve the management of acute dyspnea. One hundred ninety-six consecutive patients admitted to the hospital with a chief complaint of dyspnea were randomized to receive or not receive an echocardiogram within 24 hours of admission. Most patients randomized to echo and control groups had cardiac or pulmonary disease and were comparable in their other clinical characteristics. Predefined study end points included the following: change in diagnosis or treatment; performance of additional diagnostic cardiopulmonary studies; and duration of hospitalization (the principal end point). Changes in diagnosis or treatment during hospitalization were as infrequent among patients randomized to echo as among control patients. Echocardiography independently confirmed the clinical diagnosis in 72 percent of echo-randomized patients. Even when echo findings conflicted with the clinical diagnosis, the diagnosis and management plan rarely changed. Additional cardiac or pulmonary studies were ordered as frequently among patients randomized to echocardiography as among those randomized to control. The mean duration of hospital stay also did not differ between the two groups, and no clinical parameter served to predict which subgroup of patients might benefit from echocardiography. Although echocardiography can be expeditiously obtained during respiratory exacerbations of cardiopulmonary disease, indiscriminate echo does not necessarily hasten or alter the treatment of such patients. PMID- 2323247 TI - The clinical spectrum of Staphylococcus aureus pulmonary infection. AB - Staphylococcus aureus causes serious pulmonary infections in adults. Prior descriptions of this entity have depended on diagnosis of expectorated sputum cultures that are often contaminated. To better characterize this infection, we retrospectively reviewed the medical records of 31 adults with S aureus pulmonary infection diagnosed by culture specimens uncontaminated by the upper respiratory flora. Our results support the concept that S aureus pulmonary infections usually occur in older adults (sixth decade or older) with concomitant illnesses that are typically nosocomial. However, in contrast to previous reports, the chest roentgenograms in these patients typically showed multilobar infiltrates (60 percent), predominantly in the lower lobes (64 percent), and often bilateral (48 percent). Pleural involvement (48 percent) was more common than previously reported, and abscess formation (16 percent) occurred infrequently. Sputum cultures were found to be sensitive but nonspecific diagnostic tools. Despite antibiotic therapy, reinfection occurred in 10 percent of patients and the mortality rate was 32 percent. PMID- 2323248 TI - Cardiac arrhythmias during exercise in severe chronic obstructive pulmonary disease. AB - We studied the effect of maximal exercise on the prevalence of arrhythmias in 122 subjects with severe COPD. At rest, ten subjects had supraventricular arrhythmias while 13 had unifocal VPB greater than or equal to 6/min or ventricular bigeminy. At peak exercise, six subjects had supraventricular arrhythmias while 24 had VAs. Univariate and multivariate analysis with logistic regression did not show relationships between exercise-related cardiac arrhythmias and the severity of pulmonary disease, oxyhemoglobin desaturation or ECG evidence of chronic lung disease. Exercise-related arrhythmias were significantly associated with the presence of arrhythmias at rest and 87 percent of subjects who had no arrhythmias at rest did not have any during exercise. In patients with COPD, the development of potentially serious arrhythmias during exercise is uncommon without clinically apparent CAD or arrhythmias at rest. However, routine cardiac monitoring during exercise testing should not be abandoned in this population since VAs can occur despite their absence at rest. PMID- 2323249 TI - The spectrum of tuberculosis in a New York City men's shelter clinic (1982-1988) AB - The objective of this study was to determine the prevalence of tuberculous infection and the incidence of active tuberculosis in homeless men attending a shelter-based clinic and to examine risk factors for acquisition of infection and development of active disease. The design was a prospective cross-sectional survey. Men were evaluated by standardized interviews using a questionnaire. Where indicated, skin testing with PPD, collection of sputum for smear and culture for acid-fast bacilli, and chest x-ray films were performed. The setting was an on-site clinic at a men's shelter in New York City. The patients were men attending the clinic for physical examinations for the work program or requesting evaluation of various medical problems. A total of 1,853 men were evaluated over a 73-month period. The overall rate of infection was 42.8 percent, including 27.0 percent with a positive PPD test, 9.8 percent with a history of a positive PPD test, and 6.0 percent with active tuberculosis. Increasing age, length of stay in the shelter system, black race, and intravenous drug use were found to be independently associated with tuberculous infection. Age, length of stay in the shelter system, and intravenous drug use were independently associated with active tuberculosis. We achieved a compliance rate of 36 percent completing treatment and 13 percent receiving treatment at the conclusion of the study. PMID- 2323250 TI - The short-term effects of smoke exposure on the pulmonary function of firefighters. AB - The short-term effects of smoke inhalation have been little studied. This study evaluated whether firefighters experience a significant change in spirometric values following exposure to smoke from a fire. Sixty firefighters from the city of Pittsburgh completed a questionnaire (Medical Research Council) and underwent spirometric testing following exposure to house fires. The group contained 25 current smokers, 14 ever smokers, and 21 never smokers. Firefighters reporting cough, phlegm, breathlessness, and chest illnesses were more likely to be current or ever smokers than never smokers. Mean spirometric data obtained before exposure, after a minimum of four off-duty days, showed the following: FVC, 4.50 +/- 0.60L (90 percent of predicted); FEV1, 3.65 +/- 0.56L (96 percent of predicted); FEV1/FVC, 81 +/- 8 percent (106 percent of predicted); FEF25-75%, 3.71 +/- 1.13L/s (96 percent of predicted); and PEF, 7.95 +/- 1.70L/s (87 percent of predicted). After exposure, spirometry was performed on 22 firefighters. All spirometric values decreased after exposure; however, a significant decline was only seen in two indices, the FEV1 and FEF25-75%. This decline was small (3 to 11 percent). Two firefighters experienced an exaggerated decline in spirometric values after exposure, compared to the group as a whole. Neither age, smoking history, location of firefighting, intensity of smoke exposure, or use of a self contained breathing apparatus explained the reasons for the greater decline in these two individuals. Thus, while firefighters do experience a small decrease in pulmonary function after exposure to house fires, there appears to be a small subgroup of firefighters who develop more substantial and potentially clinically important decreases in pulmonary function after smoke exposure. PMID- 2323251 TI - Smoking and roentgenographic opacities in US Navy asbestos workers. AB - The US Navy's Asbestos Medical Surveillance Program monitors civilian and military employees with current or historical exposure to asbestos. The prevalence of definite radiologic parenchymal abnormalities (ILO category greater than or equal to 1/0) was 3.10 percent for 32,233 smokers vs 1.09 percent for 13,414 nonsmokers. The age-adjusted prevalence ratio was 2.23. The difference in prevalence between smokers and nonsmokers persisted in all age groups studied and was greatest among the oldest employees. These findings in a large population suggest that parenchymal opacifications alone will not reliably differentiate between the impacts of asbestos exposure and smoking in patients who face both risks. PMID- 2323252 TI - Agreement between noninvasive oximetric values for oxygen saturation. AB - We made an assessment of five pulse oximeters in regard to their ability to replace the HP ear oximeter as a noninvasive measurement of SaO2. Trials were performed during isocapnic progressive hypoxia (SaO2 range, 99 to 70 percent) in 22 white and six black subjects. Comparisons between values of SaO2 by oximetry were analyzed by comparing the difference of values by the two methods against their mean. The difference between pulse oximeters and the HP was 2.6 +/- 10.3 percent in all subjects. Results in whites were 1.9 +/- 10.2 percent and in blacks were 5.1 +/- 9.2 percent. The distribution of differences between pulse oximeters and the HP were larger below 80 percent than above 85 percent. We conclude that pulse oximeters give higher values than the HP, a tendency which is more pronounced in black than in white subjects. While the limits of agreement are better at saturations above 85 percent, the 95 percent confidence limits of agreement between pulse oximeters and the HP are rather large (+/- 10 percent) and unacceptable for assuming that pulse oximeters will provide the same values as found in clinical studies using the HP. PMID- 2323253 TI - The pulmonary sequelae associated with accidental inhalation of chlorine gas. AB - Twenty previously healthy individuals were accidentally exposed to high concentrations of chlorine gas in 1975. Pulmonary function tests were performed on these individuals on several occasions over the next 12 years. On average, each subject was followed up for 8.5 years and 13 of the 20 exposed persons were tested 12 years following the exposure. Pulmonary function tests obtained one day following the accident were most notable for the high prevalence of airflow obstruction and air trapping. Over the ensuing years, the airflow obstruction persisted; however, the high prevalence of air trapping resolved. Of note, the prevalence of a low residual volume consistently increased during the follow-up period (p less than 0.001) and at year 12, 67 percent of those tested had residual volumes below 80 percent of their predicted value. We also found that five of 13 subjects tested at year 12 had an increase in airway reactivity (greater than 15 percent decline in FEV1) to inhaled methacholine. Those individuals with reactive airways were older (p = 0.004) and had more marked airflow obstruction (p = 0.03) and air trapping (p = 0.03) immediately following the exposure. These data suggest that exposure to high concentrations of chlorine gas may result in long-term pulmonary complications that are characterized by a reduced residual volume. Unfortunately, these data preclude us from determining whether the chlorine exposure led to the development of airway reactivity or the presence of reactive airways accounted for the air trapping that was observed following the exposure to chlorine gas. PMID- 2323254 TI - The relationship between conductance and functional residual capacity during drug induced bronchoconstriction. AB - We wondered if the inverse changes in airway conductance (Gaw) and functional residual capacity (FRC) during histamine (H) and acetylcholine (ACH) challenge are interrelated or occur at random. In 14 normal and 14 asthmatic subjects, we determined FRC and Gaw changes corresponding to changes in specific airway conductance (SGaw) around -40 percent produced by an aerosol of H or ACH inhaled quantitatively and with measured lung deposition. We also assessed the elastic recoil following H inhalation (5A). We found that in 11 normal and nine asthmatic subjects, after H or nine normal and 11 asthmatic subjects after ACH, Gaw and 1/FRC were linearly and directly related (p less than 0.05). The steepness of this slope was directly related to the resting Gaw values. A similar relation was uncovered in the literature for asthmatic patients at rest or during recovery from natural asthma. As the elastic recoil was normal and did not change after H, it could not explain delta FRC at delta SGaw of -40 percent. IN CONCLUSION: (1) during H or ACH challenge, Gaw-FRC relationship in normal or asthmatic subjects tends to be hyperbolic and dependent on resting Gaw; (2) such a relationship is seemingly present in other bronchoconstrictor responses with a different pathogenesis; and (3) during bronchoconstriction, as Gaw vs FRC is no longer linear, SGaw becomes volume dependent. PMID- 2323255 TI - Emphysematous change in chronic asthma in relation to cigarette smoking. Assessment by computed tomography. AB - To evaluate the occurrence and the degree of emphysema in chronic asthma in relation to the effect of cigarette smoking, we examined 35 subjects with irreversible airway obstruction (17 nonsmokers and 18 smokers). We performed pulmonary function testing and CT scans on all subjects. The ES was assessed by a visual scoring system on CT scans. Between nonsmokers and smokers, there was a significant difference in the ES (p less than 0.05), but not in the FEV1, TLC, and Dsb/VA (expressed as percent predicted values). The ES was 2.3 +/- 4.7 percent (mean +/- SD) in nonsmoking subjects and 13.7 +/- 16.7 percent in smoking subjects. In all subjects the ES showed significant correlations with Dsb/VA (p less than 0.001) and pack-years of cigarette consumption (p less than 0.001) but did not show correlations with FEV1 and with TLC. We concluded that emphysema can occur in smoking asthmatic subjects because of the effect of cigarette smoking, and CT scans are useful for detecting this emphysematous change. PMID- 2323256 TI - Apneustic breathing. A characteristic feature of brainstem compression in achondroplasia? AB - We have observed apneustic breathing in five patients with achondroplasia. In contrast to experimental models of apneusis, these patients appeared to have intact vagal function and no evidence of pontine disease. However, all our patients displayed clinical, structural, and electrophysiologic features of cervicomedullary compression, a well-recognized complication of achondroplasia. The degree of apneustic breathing was reduced in the majority of our patients following decompressive surgery. Traditional theories on the pathogenesis of apneustic breathing cannot satisfactorily explain the presence of apneustic breathing in our patients. We suggest that cervicomedullary compression may be capable of producing apneustic breathing in the absence of vagal or pneumotaxic center lesions. PMID- 2323257 TI - Clinical and electrophysiologic correlates of sinus node dysfunction after orthotopic heart transplantation. Observations in 42 patients. AB - We assessed incidence and course of postoperative SN dysfunction in 42 cardiac transplant recipients. RHY, HR and CSNRT were compared in distinguishing between persistent (9 of 42 patients) and transient (11 of 42) SN dysfunction. Persistent SN dysfunction was distinguished by a significantly lower HR (day 14: 46.2 +/- 12 vs 67 +/- 19 bpm; day 21: 40.3 +/- 21 vs 70.8 +/- 16 bpm; p less than 0.05, respectively) and by RHY: postoperative AS (3 of 42) was found only in patients whose SN dysfunction persisted while patients with SR but prolonged CSNRT more often had transient impairment (6 of 42 vs 2 of 42); CSNRT, in contrast, is unlikely to be useful in distinguishing between transient and persistent SN dysfunction since exceptionally long CSNRTs (11,340 ms. 12,080 ms) occurred in patients with both types. Ischemic times were significantly longer in patients with transient impairment when compared with the group with normal SN function (155.1 +/- 36 vs 109.2 +/- 36 min, p less than 0.05) but did not differ significantly in patients with persistent SN dysfunction (124.8 +/- 32 min). Thus, (1) SN dysfunction after cardiac transplantation is common but most often transient; (2) RHY and HR are adequate follow-up parameters and best predictors of long-term SN function; (3) SN dysfunction after transplantation has important clinical implications given the unreliability of lower pacemakers to take over in 3 patients; (4) transient SN dysfunction is related to duration of ischemia during hypothermic preservation whereas pathogenesis of persistent SN dysfunction remains to be elucidated. PMID- 2323258 TI - P-wave configuration as an indicator of echocardiographic indices of cardiac structure and function in normotensive adolescents. AB - We evaluated the associations of a bimodal P-wave in ECG lead V1 to cardiac structure and function in healthy normotensive adolescents. Two-dimensional guided M-mode echocardiography, 12-lead ECG, and conventional and 2-hour averaged automated blood pressure (BP) measurements were obtained in 40 normotensive (conventional BP less than 140/90 mm Hg) adolescents (mean age, 13 +/- 1 years). Compared with subjects with simple unimodal P-waves (n = 18), those with a normal yet bimodal P-wave in lead V1 (n = 22) had higher two-hour averaged systolic BP (108 +/- 12 mm Hg vs 99 +/- 7 mm Hg, p less than 0.01) and conventional sphygmomanometer systolic BP (110 +/- 11 mm Hg vs 103 +/- 10 mm Hg, p = 0.05). Structurally, the bimodal P-wave group had greater left ventricular mass (174 +/- 40 g vs 144 +/- 26 g, p less than 0.01), and functionally, they had a greater stroke volume (68 +/- 15 ml vs 57 +/- 13 ml, p less than 0.05) than the unimodal P-wave group. In the group with bimodal P-waves, left atrial size was directly related to left ventricular mass (r = 0.63). By step-wise multiple linear regression analysis, this correlation coefficient increased to 0.74 with inclusion of heart rate and to 0.82 with inclusion of systolic BP. Although left atrial size was similar in the unimodal and bimodal P-wave groups, it was unrelated to any parameter in the unimodal P-wave group. Thus, a bimodal P-wave in lead V1, while generally considered a normal variant, is associated with slightly higher systolic BP, significantly greater left ventricular mass, and greater stroke volume. Additionally, a bimodal P-wave in V1 is predictive of the parameters that influence left atrial size, especially left ventricular mass. While all of these findings fall within the traditionally defined normal ranges, the existence of a bimodal P-wave might identify young individuals who are vulnerable to early cardiovascular manifestations of hypertension. PMID- 2323259 TI - Pulmonary Wegener's granulomatosis. A clinical and imaging study of 77 cases. AB - We studied 77 patients with biopsy-proven WG and pulmonary manifestations, to characterize the nature and frequency of the clinical, imaging and endoscopic features of this condition. Pulmonary symptoms were cough, mild dyspnea, hemoptysis and chest pain. Five patients had no pulmonary symptoms. Imaging features consisted of nodules, infiltrates and pleural opacities. A CT scan proved useful by disclosing cavities in opacities or opacities which were not seen on an x-ray film. Fiberoptic bronchoscopy was performed in 74 patients, and it was macroscopically abnormal in 55 percent (showing bronchial inflammation or stenosis or both or isolated hemorrhage). Six patients presented with alveolar hemorrhagic syndrome. Four patients had a pleural exudate rich in polymorphonuclear leukocytes. The WG was limited to the lung in seven patients. Sixteen patients died because of active disease or iatrogenic complications (two). An improved knowledge of clinical and imaging features of WG could help the clinician reach an earlier diagnosis. PMID- 2323260 TI - The assessment of major airway function in a ventilator-dependent patient with tracheomalacia. AB - A 60-pack-year smoker presented with cough, dyspnea and orthopnea of three months' duration. Spirometry revealed severe reduction in maximal expiratory flow; CT of the chest and bronchoscopy demonstrated expiratory collapse of a mid tracheal segment, and a presumptive diagnosis of tracheomalacia was made. A right lateral thoracotomy was performed to resect the unstable segment and improve maximal expiratory flow. Diffuse major airway disease with absence of cartilaginous rings from the thoracic inlet to the mainstem bronchi was encountered. The trachea and mainstem bronchi were stented externally. A high resistance to airflow and absence of expiratory flow limitation were present, suggesting a fixed rather than variable intrathoracic obstruction of major airways. This case illustrates some potential pitfalls in preoperative assessment of patients with tracheomalacia. Recordings of airway pressure and flow during mechanical ventilation are useful in distinguishing between fixed and variable intrathoracic obstruction and may complement tests of airway anatomy. PMID- 2323261 TI - The Mexican asthma cure. Systemic steroids for gullible gringos. AB - Asthmatic patients from western Canada and the United States have reported that after visits to an asthma clinic in Mexicali, Mexico, they return home substantially improved or cured having received "a bronchodilator medication unavailable in the United States or Canada because of the big drug companies." Analysis of these medications reveals that the most commonly prescribed combination is the glucocorticoid triamcinolone (unscored white tablets) and the antihistamine chlorpheniramine (coated biconvex orange or red tablets). Occasionally benzodiazepines are added to these medications. The patients are assured that the medications which they have been given are free of side effects and specifically, that corticosteroids are not used. Such therapy is dangerous to the patient who not only is unaware of the medications that he or she is taking, but is unlikely to mention this therapy to his or her physician. These patients risk drug interactions, medication side effects, and the possibility of adrenal failure either with a stress to their system or on withdrawal of drug treatment. Patients are also at risk of abandoning safer forms of asthma therapy for the miracle cure. We, too, are partially responsible for these unethical practices by avoiding the use of steroids and undertreating our patients at times, leaving them unnecessarily restricted and eager for any form of relief. PMID- 2323262 TI - Pulmonary hamartoma syndrome. AB - We reviewed 24 charts of patients with pulmonary hamartoma; numerous congenital anomalies and benign tumors were observed in this series. Most of the observed associations are known to occur in patients with Cowden's syndrome, which is characterized by multiple hamartomatous neoplasms of ectodermal, mesodermal, and endodermal origin; however, to our knowledge, there has been no reported association between pulmonary hamartoma and Cowden's syndrome. We conclude that pulmonary hamartomas are frequently accompanied by other developmental abnormalities and benign tumors. PMID- 2323263 TI - Encapsulated chest fluid moving with body position. PMID- 2323264 TI - Training in laser bronchoscopy and proposals for credentialing. PMID- 2323265 TI - An unusual presentation of hydatid disease of the lungs. PMID- 2323266 TI - Thrombolysis in cardiopulmonary disease. PMID- 2323267 TI - How to maximize the safety of coronary and pulmonary angiography in patients receiving thrombolytic therapy. AB - Patients who receive thrombolytic therapy in close temporal relationship to undergoing coronary or pulmonary angiography are at high risk of developing hemorrhagic complications, particularly at the vascular access site. A single wall percutaneous puncture technique, use of a sheath for vascular access, use of a pigtail catheter for pulmonary angiography, avoidance of a temporary pacing catheter, and shortening the duration of thrombolytic therapy will decrease these complications. However, to maximize the safety of thrombolytic therapy, invasive vascular procedures should be avoided whenever possible. PMID- 2323268 TI - [Cesarean section in pregnancy complicated by severe hepatitis and heart disease]. AB - In this article, we reported the analysis of two severe diseases complicating pregnancy: 1,918 cases of heart disease in last 36 years and 22 cases of severe hepatitis in last 16 years. The conclusion was that on active therapy and close cooperation with cardiologist, pregnancy complicated with heart disease of grade III-IV cardiac function can be taken as an indication of Cesarean section. This operation performed at a proper time is good for the mother and also the baby. The traditional idea that Cesarean section could only be done for an obstetrical reason is not quite adequate. For primiparas with severe hepatitis, a supportive therapy with fresh blood transfusion, albumin and Cesarean section under local anesthesia might be the method of choice, its mortality rate being much lower than a vaginal delivery. PMID- 2323269 TI - [Sequelae in 4122 cases of cesarean section]. AB - From 1986-1987, there were altogether 28,048 deliveries in our hospital, and there were 4,122 cases of Cesarean section, a rate of 14.69%. Early postoperative complications occurred in 522 cases (12.66%). These were namely: postpartum hemorrhage 242 cases (5.87%), postoperative morbidity 151 cases (3.66%), bladder injury during operation 6 cases (0.15%), urinary fistula 1 case, transient hematuria after operation 39 cases (0.95%). 348 Cesarean section cases were followed-up 1-3 years after operation and 44 of them were found to suffer from late complications (12.64%). These included chronic overiosalpingitis 23 cases (6.6%), parametritis 9 cases (2.58%), paracystitis 6 cases (1.7%), abdominal incision scar endometriosis 3 cases (0.86%), ectopic pregnancy 3 cases (0.86%). PMID- 2323270 TI - [Selection and evaluation of methods of anaesthesia in cesarean section]. AB - The methods of anaesthesia in 888 cases of Cesarean section from May 1985 to December 1988 were reviewed and the results analyzed according to the effect of analgesia, muscular relaxation, uterine contractions and Apgar score. It is concluded that the continuous epidural anaesthesia is best for Cesarean section, and local anaesthesia is the second choice. PMID- 2323271 TI - [Clinical study on circulating antisperm antibodies in women with recurrent abortion]. AB - Couples with a history of recurrent spontaneous abortions (RSA) were analyzed for circulating antisperm antibodies (Ab) with an enzyme-linked immunosorbent assay (ELISA), a Franklin-Dukes (F-D) and a sperm immobilization test(SIT). The three tests were positive in 31.5%, 25.9% and 18.5% for wives and 24.1%, 11.1% and 7.4% for husbands in RSA couples. There was a statistical significance (P less than 0.01) as compared with the control group. The ELISA method was found to be most sensitive, and the positive rate of antisperm antibodies in wives was higher than that in husbands. The Ab titer of RSA group varied within 1:8 approximately 1:512, with 60% above 1:32. The pregnant weeks (P greater than 0.05) did not seem to affect the antisperm Ab titer, nor did the aborting frequency. Our study suggests that antisperm Ab is one of the important causes of RSA in women. PMID- 2323272 TI - [Light and electron microscopic studies on lichen sclerosus et atrophicus of the vulva before and after treatment]. AB - Light and electron microscopic studies were carried out on 17 cases of lichen sclerosis et atrophicus of the vulva before treatment and on 8 after treatment. For comparison, normal vulval skin was obtained for examination from 3 cases undergoing plastic surgery. The affected skin, prior to therapy, showed various degrees of atrophic and degenerative changes with widening of intercellular spaces and a diminished number of desmosomes. Increased epithelial keratosis was noted and melanotic granules decreased or totally disappeared. Collagenolysis with broken fibers and degenerative changes of arteriolar walls with scarcity of nerve fibers were noticed in the dermal layer. Round cell infiltration was rather marked. Following therapy, the different layers of the involved skin showed signs of returning to normal. Pathogenesis of the disease was briefly discussed. PMID- 2323273 TI - [Outcome of the mother and baby delivered by cesarean section in pregnancy induced hypertension. Analysis of 487 cases]. AB - We analyzed the outcome of mother and baby in 487 cases of pregnancy induced hypertension (PIH) delivered by Cesarean section (CS). The indication for CS in 70 cases was simply PIH (14.4%) and 6 out of 9 antepartum eclampsia had CS. There was no maternal or fetal death. The authors suggest that CS should be done whenever eclampsia could not be put under control in order to save both mother and baby. The incidence of postpartum hemorrhage (PPH) was lower in the CS group than in the vaginally delivered group. No late PPH occurred in our CS cases. The incidence of IUGR was 30.4%. Of these IUGR cases 43 were delivered by CS. No stillbirth occurred. The number of neonatal anoxia was less than in the vaginally delivered group (P less than 0.10). PMID- 2323274 TI - Abdominal and anorectal surgery and the acquired immune deficiency syndrome in heterosexual intravenous drug users. AB - Over a period of seven years, 474 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex were admitted on 782 occasions to the St. Francis Medical Center, Trenton, New Jersey. Abdominal surgery was performed on 16 (3.4 percent) patients, 14 (88 percent) of whom were heterosexual intravenous drug users. Anorectal surgery was performed on 20 (4.2 percent), 14 (70 percent) of whom were intravenous drug users. Intravenous drug users undergoing abdominal surgery had the same types of surgical abdominal conditions that occur in the general population. None required surgery for complications secondary to cytomegalovirus, visceral lymphoma, or visceral Kaposi's sarcoma. The postoperative morbidity rate was 72 percent. The postoperative mortality rate (30 day) was 0 percent. No intravenous drug users who underwent anorectal surgery had associated anorectal malignancies or infectious diseases. Five of six homosexual patients had either an anorectal malignancy or an associated anorectal infectious disease. Anorectal wounds did not heal within one month in one third of the intravenous drug users. The rate of wound healing was inversely related to the white blood cell count. One third of the intravenous drug users undergoing anorectal surgery were dead within six months. PMID- 2323275 TI - Surgical treatment of enterovesical fistulas in Crohn's disease. AB - A review of the surgical treatment of enterovesical fistula in Crohn's disease was undertaken to evaluate its effectiveness and long-term results. Sixty-three patients, 39 men and 24 women, with a mean age of 34.4 years were identified with enterovesical fistula. They had documented Crohn's disease for a mean period of 7.0 years. Distribution of anatomic pattern was 34.9 percent ileal, 7.9 percent colonic, and 57.2 percent ileocolic. Nineteen (30.1 percent) had previous abdominal surgery for Crohn's disease. Presenting symptoms included frequency and dysuria in 93.6 percent, pneumaturia in 79.3 percent, and fecaluria in 63.4 percent; 60.3 percent of patients had all three features. Enterovesical fistula was confirmed preoperatively in 43 patients, suspected clinically in 15 patients, and diagnosed intraoperatively in 5 patients. Sixty-one of 63 patients underwent surgery with resection of the phlegmon or abscess with the diseased bowel and curettage or resection of the fistula. After curettage of the bladder defect, pelvic and bladder drainage was instituted. Coexistent fistulas, most commonly ileosigmoid, occurred in 31 patients. Intra-abdominal abscesses were found in 21 patients, of whom 15 required two-stage procedures. One patient died (mortality 1.6 percent), urine leak occurred in 3.2 percent, and wound infection occurred in 1.6 percent. Follow-up (mean, 106 months) has identified one recurrence of enterovesical fistula due to Crohn's disease, and a further recurrence from concomitant sigmoid diverticulitis. Enterocutaneous fistulas developed in 6.4 percent and 11 patients (17.4 percent) have required further resections for Crohn's disease. Surgical treatment of enterovesical fistula in Crohn's disease is a safe and effective treatment. PMID- 2323276 TI - Defecography in patients with anorectal disorders. Which findings are clinically relevant? AB - To evaluate the results and clinical impact of defecography in patients with anorectal disorders, 100 results of defecographic examinations from 92 patients were reviewed. The defecographic results were screened for the anorectal angle, defined both at rest and during straining, perineal descent, and abnormalities of the rectal configuration during straining. Anal manometry, saline infusion test, rectal capacity measurement, and anal electromyography (EMG) were also performed. There was a significant difference (P less than 0.001) both at rest (22 degrees) and during straining (12 degrees) between the two anorectal angle measurements. Incontinent patients had a larger anorectal angle, both at rest and during straining, than continent patients (P less than 0.04), but with a large overlap. The anorectal angle was not influenced by gender or age. An abnormal rectal configuration was found in 62 defecographic examinations. From the 8 patients with rectopexy performed for a large rectocele or intussusception, incontinent patients with an intussusception had the best results. In four patients, anal EMG showed an increased activity of the external sphincter during straining. Two of these four patients had abnormal defecograhic results. No correlations were found between anorectal angle and the other function tests. In conclusion, the anorectal angle lacks clinical relevance. In patients with defecation problems, defecography may be indicated whenever other investigations (physical examination, anal manometry, anal EMG) have excluded local pathology or a spastic pelvic floor syndrome. In these situations, defecography could detect an intussusception, which could easily be treated with rectopexy. PMID- 2323277 TI - A prospective study of the accuracy of preoperative computed tomographic staging of patients with biopsy-proven rectal carcinoma. AB - From June 1983 to January 1986, 91 patients with biopsy-proven adenocarcinoma of the rectum had computed tomographic scans of the pelvis performed before treatment as part of a "sandwich" radiotherapy-surgery regimen. Two experienced diagnostic radiologists performed locoregional staging of all scans according to the University of California at San Francisco criteria; one of these radiologists repeated this staging at a later time to test the reproducibility of a single observer. Staging was performed without the use of any other radiographic studies or of any clinical information except the patients' age, sex, and the diagnosis of rectal carcinoma, to test the value of computed tomographic scans alone for staging. Agreement between the two stagings performed by the first observer was 51 percent, and interobserver agreement was only 37 percent. Agreement with Dukes' staging was only 33 percent. Therefore, preoperative pelvic computed tomographic scanning of primary rectal adenocarcinoma should not be relied upon for staging or for the selection of patients for treatment options. PMID- 2323279 TI - A prospective cohort study on the development of colorectal cancer after gastrectomy. AB - A prospective cohort study was conducted to examine whether an association exists between gastric surgery and the subsequent development of colorectal carcinoma. One thousand nine hundred twenty-seven patients (1316 men and 611 women) who had undergone curative gastrectomy for gastroduodenal diseases in the First Department of Surgery, Tottori University Hospital, during the 18-year period from 1964 to 1981, were followed to determine the incidence of the development of large-bowel carcinoma after gastric surgery. The age-, sex-, and calendar specific population at risk was calculated by the person-years method. The observed number of colorectal cancers after gastrectomy was 19 (15 men, 4 women) compared with 9.69 expected carcinomas. The difference between the observed and expected numbers was statistically significant. The authors believe that patients with previous gastrectomy are at high risk for colorectal carcinoma. PMID- 2323278 TI - Anastomotic compression button: a new mechanical device for sutureless bowel anastomosis. AB - The anastomotic compression button is a new mechanical device that uses three interlocking polypropylene buttons to produce a sutureless bowel anastomosis. The device is unique in that it allows application of the buttons via a device similar to the popular intraluminal stapler, but it leaves no staples or foreign body of any kind in the bowel wall. The authors compared the 25-mm anastomotic compression button with the 25-mm intraluminal stapler in the colon of dogs. After 28 days, the mucosal blood flow, burst pressure, and anastomotic indices were found to be identical between the anastomotic compression button and the stapler. The anastomotic compression button was easier to use, and microscopic examination showed less ulceration, fibrosis, and inflammation, and better re epithelialization at the anastomotic compression button site. The anastomotic compression button appears to have the potential to be a superior method compared with stapled anastomoses in the colon. PMID- 2323280 TI - Immunologic conditions and infectious complications in colon and rectal surgery for neoplasms. AB - The authors evaluated the peroperative immunologic state of patients with colorectal tumors and controlled the postoperative incidence of infections. Twenty-one patients were studied, and delayed type hypersensitivity reactivity determined by the CMI multitest (Merieux) eight days before and eight days after surgery. A lymphocytogram was performed using monoclonal antibodies. A significant percentage of patients were anergic preoperatively. Immunologic analysis revealed lymphocytosis in the first postoperative period. The largest absolute quantitative increase was shown by NK CD16+ cells. It is possible that the results, obtained by dynamic monitoring of the main parameters of cellular immunity, will offer a new way for prognostic evaluation of surgical risk. PMID- 2323281 TI - Colonic obstruction secondary to incarcerated spigelian hernia. Report of a case. AB - A previously unreported case of colonic obstruction secondary to incarcerated spigelian hernia is presented. The diagnosis was suspected preoperatively, based on the results of a barium-enema examination. Available diagnostic techniques are reviewed. PMID- 2323282 TI - Implantation of a benign rectal villous adenoma in the surgical track after transsphincteric excision. Report of a case. AB - A 56-year-old male patient underwent excision of a rectal villous adenoma by a transsphincteric approach. Six years after surgery, an extrarectal mucinous mass was noted, which, on biopsy, had histologic features of implantation of benign villous adenoma within the operative scar. For medical reasons, surgery was avoided and the lesion enlarged until symptoms necessitated rectal excision five years later. Histologic examination of the resected mucinous tumor supported an origin from implanted adenomatous epithelium. This is apparently the first description of implantation of an adenoma in the surgical track. Care should be taken during transsphincteric and transsacral excision of rectal adenomas to prevent implantation at the time of surgery. PMID- 2323283 TI - Sphincter preservation in rectal sarcoma. AB - Leiomyosarcoma of the rectum is rare. The standard treatment is abdominoperineal resection and, in the past, radiation therapy has been employed in the palliative setting only. The authors report two additional cases of this rare tumor and its treatment using sphincter-preserving surgery and radiation therapy. In selected patients, conservative surgery followed by radiation therapy (brachytherapy with or without external beam radiation) may be an alternative to radical surgery with the goals of local control of the disease and rectal sphincter preservation. However, more experience and longer follow-up are needed before this approach could be recommended routinely. PMID- 2323284 TI - Congenital pelvic arteriovenous malformation: an unusual cause of rectal pain. Report of a case. AB - The differential diagnosis of rectal pain is extensive, and etiologies range from common anorectal disorders to more complex pelvic floor dysfunctional syndromes. The authors present a case of a man with rectal pain secondary to a congenital pelvic arteriovenous malformation. These malformations are rare and, to the authors' knowledge, have not been reported in association with rectal pain. PMID- 2323285 TI - Vaginography: an easy and safe technique for diagnosis of colovaginal fistulas. AB - Colovaginal fistulas are often difficult to demonstrate. Vaginography is a simple, safe, and effective technique. PMID- 2323286 TI - New method for low transection of the rectum. AB - A method for low transection of the rectum within a narrow pelvis is described using the new GIA 90 autosuture instrument. PMID- 2323287 TI - Ileostomy with the EEA stapler. AB - The EEA instrument was used to perform ileostomy in three patients. Two female patients with complications of Crohn's colitis underwent total colectomy and proctocolectomy, respectively. The first patient was operated upon because of toxic megacolon and the second patient for severe perianal disease. A third male patient underwent total colectomy for severe ulcerative colitis that failed to respond to medical therapy. In all patients, ileocutaneous anastomosis was performed with the EEA stapler (ILS, Ethicon). No serious complications were observed except for slight retraction of the ileostomy in one patient after he had gained 22 pounds. PMID- 2323288 TI - Simple method for stapled low colorectal or coloanal anastomosis. AB - A technique of stapled low colorectal or coloanal anastomosis is described, which follows eversion through the anus and stapled closure of the anorectal or anal remnant. The procedure is rapid and safe, and allows a secure distal clearance under direct visual control when dealing with tumors of the lower third of the rectum. PMID- 2323289 TI - Primary repair vs. colostomy for the treatment of colon injuries. PMID- 2323290 TI - The use of gastric salvage cytology in the diagnosis of malignancy: a review of 731 cases. AB - Over an 8-yr period at the Houston Veterans Hospital, 731 endoscopic gastric salvage cytologies were performed in 671 patients, with surgical biopsy also done in 660. Seventy-six patients subsequently had tissue biopsy-proven or resection proven malignancies. Salvage cytology had a sensitivity of 91% and a specificity of 100% for the detection of primary adenocarcinoma. Biopsy alone had a sensitivity of 92%; endoscopic gastric salvage cytology and surgical biopsy combined had a sensitivity of 100% in both primary and metastatic neoplasms. This study shows that the combination of endoscopic biopsy and salvage cytology increases the diagnostic accuracy for gastric carcinoma. Gastric salvage cytology requires minimal disruption of the routine endoscopic procedure and is therefore an easier and more rapid cytologic technique than gastric brushing cytology. PMID- 2323291 TI - Transbronchial needle aspiration biopsy in the diagnosis of pulmonary neoplasms. AB - To evaluate the usefulness of transbronchial needle aspiration biopsy (TBNAB) in the primary diagnosis of lung cancer, we undertook a prospective study of this technique, assessing specimens from 124 patients over a 3-yr period. Cytologic and/or histologic material obtained by an alternate technique was available for 105 (84.7%) of the patients. The diagnostic sensitivity of TBNAB was comparable with that of other bronchoscopic techniques; with the addition of TBNAB, the overall sensitivity of bronchoscopy was increased from 54% to 72% (P less than 0.001). Because of its usefulness for diagnosis of submucosal tumors and its safety, we conclude that TBNAB is a useful addition to current methods for the diagnosis of suspicious pulmonary lesions. PMID- 2323293 TI - Cytologic features of atypical mesothelial cells in peritoneal dialysis fluid. AB - From February 1988 through October 1988, 23 samples of peritoneal dialysis fluid from 20 patients with end-stage renal disease were cytologically analyzed in an attempt to determine the effect of the dialysate on the mesothelial cells lining the peritoneal cavity. The patients, five female and 15 male, ranging in age from 26 to 75 yr, had been on continuous ambulatory peritoneal dialysis (CAPD) from 1 mo to 6 yr, 4 mo. The patients had no history of cirrhosis, neoplastic disease, radiation and/or chemotherapy, or current findings of infection. Smears and cytosieve filter preparations were made. Smear analysis included the mesothelial cell pattern, the degree of mesothelial cell atypia, and the presence of atypical multinucleated cells and mitoses. In the majority of the fluid samples, reactive mesothelial cells were arranged singly and in sheets. Moderately and severely atypical mesothelial cells were glandular and papillary in configuration. All samples contained at least a few reactive mesothelial cells; in six, the highest degree of cellular atypia was moderate; in 17, it was severe. The development of severe cellular atypia did not appear to be time dependent (a finding noted in samples from patients on dialysis for 6 mo up to 6 yr). When present, multinucleated mesothelial cells showed moderate to severe atypia. In four cases mitotic figures were present. On the basis of these findings, it is proposed that peritoneal dialysis plays a role in the development of mesothelial cell atypia. PMID- 2323292 TI - Rates of condyloma and dysplasia in Papanicolaou smears with and without endocervical cells. AB - A retrospective study of 36,853 Papanicolaou smears recorded in our laboratory during the latter half of 1988 was undertaken to assess the effect of the absence or presence of columnar endocervical cells on the detection rate of cervical condyloma acuminatum and squamous dysplasia. We found that condyloma was diagnosed only slightly more frequently in smears with endocervical cells than in those without. However, cervical intraepithelial neoplasia was detected 2.3 times more frequently in smears with endocervical cells. The disparity in detection rate increased with higher grades of dysplasia. A significant difference in detection rate was maintained in all age groups except teenagers and patients 60 yr old and above. This suggests that smears lacking endocervical cells are less sensitive in screening for dysplasia and should be repeated when clinically appropriate. PMID- 2323294 TI - Light and electron microscopic examination of fine-needle aspirates in the preoperative diagnosis of osteogenic tumors: a study of 21 osteosarcomas and two osteoblastomas. AB - Twenty-three patients with primary osteogenic tumors, two osteoblastomas and 21 osteosarcomas, underwent fine-needle aspiration biopsy in the preoperative investigation. The cytologic features in smears were compared with the light and electron microscopic findings of resin-embedded fine-needle aspirates (16 cases) and the histopathologic findings of the surgical specimens. Cytologic smears clearly indicated a primary bone malignancy in all 20 high-malignancy osteosarcomas. In the osteoblastic osteosarcomas, the diagnosis of osteosarcoma was strongly suggested by the osteoblastic appearance of the tumor cells and the presence of an osteoid-like fibrillar matrix in 6 of 11 cases in the May-Grunwald Giemsa-stained smears. The distinction of chondroblastic osteosarcomas from high grade chondrosarcomas and of polymorphic osteosarcomas from malignant fibrous histiocytomas is difficult in smears. Electron microscopic examination and immunocytochemistry indicating a positivity for vimentin but not for cytokeratin helped to exclude the possibility of a carcinoma in osteoblastic osteosarcomas where the tumor cells had epithelium-like features in the smears. The resin embedding technique of fine-needle aspirates was useful for the typing since it gave additional light microscopic information about growth pattern, structure, and matrix production, as well as ultrastructural information about cell and tissue differentiation. The osteoid-like material seen in May-Grunwald-Giemsa stained smears could be proven to represent osteoid with varying degrees of calcification at the ultrastructural examination. The fine-needle aspiration technique, especially when used for both smears and embedding, may play an important role in the preoperative investigation of bone tumors, provided that it is used with full knowledge of the clinical and radiographic findings. PMID- 2323295 TI - Diagnosis of lymphoma and reactive lymphoid hyperplasia by immunocytochemical analysis of fine-needle aspiration biopsy. PMID- 2323296 TI - Hydatid cyst: primary diagnosis by fine-needle aspiration biopsy. AB - Two cases of soft-tissues echinococcosis are presented in which the definitive diagnosis was established by identifying laminated layer remnants on fine-needle aspiration smears. Large polygonal pieces of acellular material with delicate parallel striations were seen, while neither scolices nor hooklets were found. The cases reported most likely represent the occurrence of sterile hydatid cysts. A diagnosis of echinococcosis should be considered when fragments suggestive of laminated layer are identified on smears, even in unusual sites and without evidence of hooklets and/or scolices. PMID- 2323297 TI - Tissue imprints in surgical pathology: a rapid intraoperative diagnostic aid. AB - We studied the intraoperative diagnostic value of imprint cytology in 230 samples obtained from surgical specimens submitted for frozen section diagnosis. A rapid hematoxylin-eosin stain was used. Intraoperative imprint cytology achieved an accuracy rate of 94.3%; for benign lesions the accuracy was 97.5%, and for malignant lesions it was 91%. Overall, the false-negative and suspicious-for malignancy rates were 1.3% and 4.3%, respectively. No false-positive results were found. The diagnostic yield when intraoperative imprint cytology and frozen section were used together was 99%. It is apparent that imprint cytology is a quick and simple method with wide applicability in the histopathologic diagnosis of lesions from all organs. The value of the method is enhanced when it is used with frozen section diagnosis. PMID- 2323298 TI - Angiosarcoma of the heart: pericardial fluid cytology. AB - The unique cytomorphologic aspects of a cardiac angiosarcoma in pericardial fluid are presented. Smears and cell block preparations revealed clusters of malignant pleomorphic oval to spindle-shaped cells concentrically layered about amorphous acellular cores. The cytologic findings were correlated with histologic, immunohistochemical, and electron microscopic findings in the necropsy material. PMID- 2323299 TI - Rapid microwave-stimulated fixation of fine-needle aspiration biopsies for transmission electron microscopy. AB - A new technique is described in which fine-needle aspiration biopsies are processed for transmission electron microscopy within 2 hr. This rapid processing method includes exposure of the biopsy in a glutaraldehyde-formaldehyde mixture to microwaves for 25 sec in a domestic oven. The specimen is then routinely stained, processed through graded ethanol, and embedded in epoxy resin to produce excellent preservation of fine structural features. PMID- 2323300 TI - Urothelial grade I atypia. PMID- 2323301 TI - "Thick" cell membranes revealed by immunocytochemical staining: a clue to the diagnosis of mesothelioma. AB - The distinction of malignant mesothelioma from metastatic adenocarcinoma in pleural effusions and biopsies is frequently a diagnostic problem. Immunocytochemical staining of 13 malignant mesotheliomas, eight primary adenocarcinomas of the lung, five metastatic adenocarcinomas of the lung, and 20 primary adenocarcinomas in extrapulmonary sites with a monoclonal antibody to epithelial membrane antigen (EMA) revealed "thick" cell membranes in all cases of mesothelioma. This distinctive pattern of staining was seen in the periphery of cell clusters and circumferentially around individual cells in cytologic preparations, cell blocks, and tissue sections. Intracellular and intercellular acini were also outlined by anti-EMA, and long intraluminal microvillous projections were demonstrated. Weak cytoplasmic staining was only rarely seen in mesothelioma cells. This membranous staining pattern was not observed in adenocarcinomas, which displayed strong and diffuse cytoplasmic staining. The immunocytochemical demonstration of thick and spiky membranes circumferentially disposed around individual cells corresponds to aberrant microvilli, a diagnostic clue in the recognition of malignant mesothelioma. PMID- 2323302 TI - Self-report vs. laboratory measures of aggression as predictors of substance abuse. AB - Measures of aggressive behavior, antisocial personality, criminality, and impulsivity were obtained on a sample of 85 drug abusing volunteers for studies at the Addiction Research Center in Baltimore. Measures included the Buss-Durkee Hostility Inventory, Diagnostic Interview Schedule Antisocial Personality Disorder diagnosis, Elliott-Huizinga Lifetime Events Scale, Eysenck's Impulsiveness-Venturesomeness-Empathy scales, and a laboratory measure of aggression patterned after the Buss 'aggression machine'. All of the self-report measures of aggression and antisocial personality were moderately correlated with each other, but did not correlate with the laboratory aggression measure. This laboratory measure, nevertheless, made a significant contribution to the prediction of certain substance abuse diagnoses over and above the contributions of the other measures. PMID- 2323303 TI - Effects of self-reported drug use and antisocial behavior on evoked potentials in adolescents. AB - From a sample of 35 adolescents, 17 were chosen who represented extremes of self reported drug use and delinquent behavior. Three comparison groups were derived: Group 1, n = 7, high drug use/high delinquency; Group 2, n = 4 no drug use/high delinquency; Group 3, n = 6, no drug use/no delinquency. The three groups were similar for age, IQ, race and neighborhood characteristics. Group 1 showed significantly more drug use than Groups 2 and 3; Groups 1 and 2 had comparable levels of delinquency which were significantly greater than Group 3. The subjects performed the auditory oddball task under conditions of low and high background noise. In the high background noise condition, Group 1 had longer latency P300 responses than Groups 2 and 3, while Group 2 had smaller N100 amplitude than Groups 1 and 3. Performance was similar for each group and no group differences occurred in the low background noise condition. The results support and extend previous research on the relationship between attentional and cognitive processes, and delinquent and drug using behaviors. PMID- 2323304 TI - Characteristics of women receiving mandated treatment for alcohol or polysubstance dependence in Massachusetts. AB - Characteristics of the first 20 women consecutively admitted for treatment for alcohol or polysubstance dependence following civil commitment by Massachusetts courts were studied. Women were diagnosed as either alcohol dependent (n = 12) or polysubstance dependent (n = 8). Alcohol dependent women were older at initial alcohol use, onset of regular alcoholic use, first treatment admission, and at this admission. For the group as a whole 75% had completed high school; 50% were divorced and 35% were supported by public assistance. Seventy-five percent had a family history of alcoholism. This sample of women who received court-ordered alcohol and polysubstance dependence treatment had multiple social, psychological, legal and health problems. PMID- 2323305 TI - Schedule-induced oral self-administration of cocaine and ethanol solutions: lack of effect of chronic desipramine. AB - Groups of rats drinking either solutions of cocaine HCl (0.16 mg/ml), ethanol (2.5% v/v), or water, drank excessive, equivalent volumes in daily, 3-h sessions of food-pellet delivery under a fixed-time 1-min (FT 1-min) schedule. During single-session exposures to pellet-delivery schedules using longer inter-pellet values (FT 3- or 5-min probe sessions), the cocaine and ethanol groups, but not the water group, drank greater ml/pellet amounts, confirming previous research. Inasmuch as enhanced ml/pellet intake during the greater FT probes correlated with the abuse potential of the drinking solution in previous research, the effect of chronic desipramine HCl (2 mg/kg, i.p. daily) on this enhanced intake response was determined. For all groups, chronic desipramine treatment (2 mg/kg was judged to be the maximum dose free of non-specific, suppressive effects) affected neither FT 1-min schedule-induced polydipsia nor did it affect the enhanced ingestional response to the greater FT probes for the cocaine and ethanol groups. Chronic administration of desipramine may have therapeutic efficacy in treating cocaine abuse only in subjects attempting to refrain from cocaine who are aided in their passage through a withdrawal phase by desipramine. PMID- 2323306 TI - Effects of sublingually given naloxone in opioid-dependent human volunteers. AB - To determine whether sublingual naloxone could precipitate withdrawal in opioid dependent subjects, naloxone was administered in increasing doses (0-8 mg in four or six sessions conducted over 2 days) to six heroin abusers and three methadone (30 mg/day, p.o.) maintenance patients. Two or three sessions were conducted per day with 2- to 2.5-h intervals between same-day sessions. Naloxone precipitated withdrawal in two of six heroin abusers and in all three methadone subjects. Naloxone is sufficiently absorbed sublingually to precipitate abstinence in dependent subjects, but naloxone doses up to 1-2 mg can be administered sublingually to opioid abusers/addicts without precipitating withdrawal. PMID- 2323307 TI - Diploma in addiction behaviour: update. AB - The Diploma in Addiction Behaviour, offered by the Institute of Psychiatry of the University of London, began in 1986. We are now recruiting for the fourth year, 1989/90. Although its primary objective remains to 'train the trainers', this 'experiment in action' has in itself catalysed changes in the structure and goals of the programme. These include balancing the academic and clinical training, in which placements will be both hospital-based and community-orientated. Student participation will be maximised, and the experience of their own country emphasised. Training for leadership emerges as an important module, as does the process of learning about research skills. PMID- 2323308 TI - Stasis pigmentation and chronic alcoholism. PMID- 2323309 TI - Alcohol, AIDS risks and commercial sex: some preliminary results from a Scottish study. AB - During 1988 self-report data were elicited from a study of 102 male and 103 female sex workers (prostitutes) in Edinburgh. Respondents were contacted by 'snowballing', mostly in licensed premises. This was reflected by high levels of self-reported alcohol and illicit drug use. Respondents reported that both alcohol and illicit drug use were commonplace in relation to their work and that many of their clients were under alcohol or drug effect at the time of contact. Condom use was unrelated to sex workers' alcohol or drug use, but was significantly associated with sex workers' assessments of the proportions of their clients also under the influence of illicit drugs. PMID- 2323310 TI - [Biophysical membrane correlates of tolerance and dependence on alcohol]. AB - A large number of studies have given clear indications that ethanol does affect the physicochemical properties of the membrane. Membrane reorganization and adaptation can develop against the acute disordering effect of ethanol during chronic intoxication. Nevertheless, there has been so far no direct evidence of correlations between functional tolerance or dependence and membrane physical states. Membrane physical state can be assessed by fluorescence polarization of DPH in the absence (measure of membrane 'fluidity') or presence (measured of membrane sensitivity) of ethanol added in vitro. Functional tolerance has been already correlated with a reduced synaptic membrane sensitivity to ethanol (membrane tolerance). Behavioural dependence was shown to be quantifiable by measurement of alcohol intake in a free choice situation (water/alcohol) solution). This dependence model allowed us to define a membrane dependence which consists in an increased membrane rigidity (or decrease in 'fluidity') persistent after withdrawal, and which was correlated to the intensity of the behavioural dependence. This biophysical expression of dependence seems rather independent of the biophysical membrane tolerance (resistance to the acute ethanol fluidizing effect), which was found to be rapidly reversible after withdrawal and re-induced by alcohol re-intake, requiring recent periods of current abuse to be expected. PMID- 2323311 TI - Are the effects of chronic ethanol administration on erythrocyte membrane mediated by changes in plasma lipids? AB - The effect of chronic ethanol consumption on plasma and erythrocyte membrane lipids were studied in rats fed a liquid diet containing ethanol for 4 weeks and intubated with the same diet 90 min prior to killing. Control animals underwent the same treatment, except that their liquid diet did not contain ethanol, but an isocaloric amount of carbohydrates. Plasma total cholesterol, free (unesterified) cholesterol and HDL cholesterol were higher in ethanol-fed animals than in controls. Phospholipids were also higher in the plasma of ethanol-fed animals when compared to controls so that the plasma cholesterol/phospholipid ratio (Ch/PL ratio) of the two groups did not differ significantly, regardless of the cholesterol fraction considered. Experimental and control animals did not differ either in the Ch/PL ratio of their erythrocyte membranes. In view of the fact that it has been suggested that the factor determining the direction of the cholesterol exchanges between plasma and erythrocyte membranes is the equilibrium between their respective Ch/PL ratios, these results are interpreted as being compatible with the hypothesis that the effect of chronic ethanol intake on erythrocyte membrane lipids is mediated through changes in plasma lipids. PMID- 2323312 TI - Opioid antagonist challenges in buprenorphine maintained patients. AB - Following one month of sublingual buprenorphine treatment, 15 patients at either 2 mg (n = 7) or 3 mg (n = 8) were hospitalized and the buprenorphine was abruptly stopped by placebo substitution. On the morning following their last dose of buprenorphine, 10 patients were given 1 mg oral naltrexone and 5 were given 0.5 mg/kg intravenous naloxone in a double blind placebo controlled challenge. The naltrexone challenges produced no increase in opioid withdrawal symptoms, plasma MHPG levels, or blood pressure compared to placebo, while naloxone produced significant symptoms and blood pressure increases compared to placebo challenges. PMID- 2323313 TI - Association between intravenous drug use and early misbehavior. AB - This investigation uses an epidemiologic strategy to examine a suspected association between misbehavior in early life and subsequent involvement in intravenous drug use. The 222 cases of i.v. drug use in this study were a subset of all persons recruited for a continuing study of drug use, HIV-1 infection, and the natural history of AIDS. It was possible to match these 222 i.v. drug users to 588 subjects from the NIMH Epidemiologic Catchment Area survey sample, for a total of 810 subjects in 60 matched sets. The matching factors were gender and census tract of residence. Conditional logistic regression models were used to estimate the degree of association between early misbehavior and i.v. drug use. The results showed a strong association between i.v. drug use and early misbehavior. For every unit increase in misbehavior score, the odds of being an i.v. drug user increased by a factor of 1.74 (P less than 0.001). Compared to subjects with low misbehavior scores, those with high scores were 24.67 times more likely to be i.v. drug users (P less than 0.001). Results of this study add to evidence now supporting field trials of public health strategies to modify the link between misbehavior in early life and later illicit drug use. PMID- 2323314 TI - Clinical and prognostic value of serum procollagen levels in chronic alcoholic liver disease. AB - Liver fibrogenesis involves the synthesis of collagen fibrils and proteoglycans by various types of liver cells, including Ito cells, transitional cells, myofibroblasts and hepatocytes. Synthesis of collagen fibrils follows a complex metabolic pathway with intermediate products such as type III procollagen (III PC). Serum levels of III-PC may reflect the activity of the fibrogenetic process. We analysed the relationship between the serum levels of III-PC (N-terminal peptide) and diverse clinical, biochemical and histological parameters of 77 alcoholic patients (27 cirrhotics), comparing them with those of 15 age- and sex matched controls. A highly significant difference was obtained between controls and patients (P less than 0.0001), but no differences were observed between cirrhotics and non-cirrhotics. Serum III-PC significantly correlated with clinical and biochemical data of liver function derangement (prothrombin activity, serum albumin, bilirubin, gynecomastia, ascites, encephalopathy, edema, splenomegaly); with the duration of ethanol addiction and with MCV. Sixty patients were followed up for a period ranging between 3 and 1056 days (mean = 356 days); 9 of them died. Patients with III-PC levels above 38 ng/ml had a significantly higher mortality (P = 0.006) than those with levels under 38 (log rank test). Thus, serum III-PC may be a useful tool in the clinical evaluation and prognostic assessment of patients with chronic alcoholic liver disease. PMID- 2323315 TI - Concurrent and simultaneous use of alcohol with cocaine: results of national survey. AB - The purpose of the present study was to determine the prevalence of the concurrent and simultaneous use of alcohol and cocaine in the general population and to examine differences in these rates between important sociodemographic subgroups. The results indicated that a sizable proportion of Americans were engaged in both substance use patterns. The population estimate for simultaneous use of both substances (i.e., simultaneously or on the same occasion) was approximately 4 million for the month preceding the interview, rising to approximately 9 million when the past year timeframe was considered. Corresponding figures for the concurrent use of alcohol and cocaine (i.e., use of both substances during the same time period) were approximately 5 million during the past month and 12 million during the past year. The extent of each substance use practice varied as a function of sociodemographic factors. Implications of these findings are discussed in terms of the need for age-sex-ethnic-specific prevention strategies. The need for future analytic epidemiologic research to determine the precise relationship between dose, frequency and duration of concurrent and simultaneous use and each adverse consequence is emphasized. The need for longitudinal research in the general population is also highlighted. PMID- 2323316 TI - [Repeated kidney transplantation. Surgical technic, results and complications]. AB - Third renal transplants were performed in 31 patients (25 men and 3 women: mean age 33 +/- 11 years) with terminal renal failure. Surgical complications occurred in four of them. Acute rejection crises were frequent (48%). In three cases acute humoral vascular rejection led to loss of the grafted kidney. One patient died within 3 months. The proportion of functioning transplants was 83% at 3 months, 59% at 1 year and 20% at 5 years. Such factors as the concentration of panel reactive antibodies, a history of previous acute humoral rejection crises or the timing of the previous transplant loss had no influence on the prognosis of the new graft. After a mean observation period of 35, 4 months patients whose HLA-DR antigens matched those of the donor at one or two loci had a markedly higher proportion of functioning renal transplants (69% and 64%, resp.) than patients without HLA-DR compatibility (0%; P less than 0.01). These results indicate that a third renal transplant does not carry any increased perioperative risk, and that the proportion of functioning transplants is good in the short term, though the long-term results are poor. Prolonged survival of the renal transplant can be expected only if there is an optimal HLA-DR match between donor and recipient. PMID- 2323317 TI - [Bone pain in adults as the first symptom of late congenital syphilis]. AB - A 20-year-old woman developed multifocal bone pain. Diagnostic radiology revealed thickened periosteum, and syphilis serology was positive (T. pallidum haemagglutination test 1:5120). She also had discrete signs of congenital syphilis, with retinitis pigmentosa and Hutchinson's incisors. Skeletal scintigraphy demonstrated increased uptake even in radiologically unremarkable bones. The bone pain decreased after four-week administration of 1 M units of penicillin G daily. Scintigraphy one year later showed regression of the increased uptake, skeletal radiology did not reveal significant changes. This case shows that late manifestations of congenital syphilis still occur today. The stigmata of such an infection can be minute and easily missed. Skeletal scintigraphy is better for demonstrating active bone involvement than conventional radiology. PMID- 2323318 TI - [Care of a peripheral indwelling catheter]. PMID- 2323319 TI - [Hypercholesterolemia and coronary heart disease]. PMID- 2323320 TI - [Endobronchial dose of adrenalin]. PMID- 2323321 TI - Pade-Laplace method for the analysis of time-resolved fluorescence decay curves. AB - The interpretation of fluorescence intensity decay times in terms of protein structure and dynamics depends on the accuracy and sensitivity of the methods used for data analysis. The are many methods available for the analysis of fluorescence decay data, but justification for choosing any one of them is unclear. In this paper we generalize the recently proposed Pade-Laplace method to include deconvolution with respect to the instrument response function. In this form the method can be readily applied to the analysis of time-correlated single photon counting data. By extensive simulations we have shown that the Pade Laplace method provides more accurate results than the standard least squares method with iterative reconvolution under the condition of closely spaced lifetimes. The application of the Pade-Laplace method to several experimental data sets yielded results consistent with those obtained by use of the least squares analysis. PMID- 2323322 TI - Biophysical models of ciliary activity: Gaussian frequency distributions. AB - A model of a freely rotating extended scatterer is proposed to describe light scattering from beating cilia. Gaussian rotation frequency distributions, characterized by a mean angular frequency and a standard deviation, are introduced in order to simulate intensity autocorrelation functions and to fit the model to experimental data. Thus the ciliary beats are characterized by a mean beat frequency and a standard deviation of the beat frequency distribution. The standard deviation influences the damping of the intensity autocorrelation function of light scattered from cilia. The calculated intensity autocorrelation function shows a more prominent oscillating behaviour the smaller the standard deviation of the beat frequency. The validity of the model is supported by experimental data in two ways: 1) The model fits very well to experimental data in computer evaluations, 2) Neither the model nor information obtained from measurements are dependent on the measuring angle. PMID- 2323323 TI - Influence of altered phospholipid composition of the membrane outer layer on red blood cell aggregation: relation to shape changes and glycocalyx structure. AB - Reversible aggregation of erythrocytes was investigated after alteration of the phospholipid content in the membrane outer leaflet either by disturbance of endogenous transmembrane lipid asymmetry through changes in cellular free calcium, or by incorporation of exogenous lyso-derivatives. It was found that both calcium loading and lyso-phosphatidylcholine (LPC) addition induce a strong increase in red cell-red cell adhesive energy, whereas lyso-phosphatidylserine (LPS), added in the same amount as LPC, does not. Red cell morphological studies show differences in the shape change efficiency of LPS, LPC and calcium loading. However, it was further demonstrated that shape change is not directly responsible for the observed adhesive energy increase, since neuraminidase or trypsin treatment abolish this increase, even though the shape changes induced by alteration of phospholipid organization are not affected. The latter experiment strongly suggests that the red cell adhesive energy increase results from an alteration of the glycocalyx structure, which could be in turn a consequence of the shape change. PMID- 2323325 TI - Efficacy of behavioral management and patient education on vascular access cleansing compliance in hemodialysis patients. AB - Compared four treatment conditions to test their ability to enhance compliance with vascular access cleansing (VAC) procedures in a group of 56 hemodialysis patients. The conditions were patient education, behavioral management with monetary incentive, patient education/behavioral management, and attention control. Behavioral observers rated VAC behavior at pretreatment, posttreatment 1 month follow-up, and 1-year follow-up. Knowledge of VAC procedures was also assessed via a questionnaire at pretreatment and posttreatment. Data were analyzed using repeated-measures multivariate analyses of variance. Results indicated that the patients in the education/behavioral, behavioral, and education groups gave significantly more correct answers on our VAC knowledge questionnaires at posttreatment than did patients in the attention control group. Further, patients in the education/behavioral and behavioral groups completed significantly more VAC steps at posttreatment and 1-month follow-up than did patients in the education group and in the attention control group. Differences were not maintained at 1-year follow-up, although more than 50% of the patients were lost to follow-up. Implications of the present findings for behavioral and educational interventions are discussed. PMID- 2323324 TI - Effects of decisional control and work orientation on persistence in preventive health behavior. AB - Examined persistence in the daily use of fluoride mouthrinse among adolescents as a function of an induced-choice manipulation concerning self-management strategies and freedom to participate in the program. Seventh-grade boys and girls from urban and suburban schools were randomly assigned to a series of either high- or low-choice decisional control manipulations; their daily, home use of fluoride was monitored over a 20-week period. In order to ameliorate the relatively lower persistence rates found previously among suburban (vs. urban) students, all students were given self-management and action instructions as per previous studies. Although suburban students still declined in persistence relative to urban students, female students who received high choice persisted at a higher rate than girls who received low choice. Boys, for the most part, were unaffected by the manipulation. In addition, students' self-reported work orientation was also positively associated with persistence. PMID- 2323326 TI - Age-related differences in cardiovascular reactions to mental stress tests in women. AB - Tested 84 healthy, sedentary women in the laboratory during performance of difficult and easy problem-solving tasks. They were divided into three age groups: 19 to 32 years, 33 to 43 years, and 44 to 60 years (n = 28 women per group). Baseline systolic blood pressure (SBP) and diastolic blood pressure increased with age, whereas skin conductance level was lower in older women. In addition, initial SBP reactions to tasks were positively related to age, even after controlling for baseline blood pressure, aerobic fitness, and Framingham Type A Scale behavior scores. There were no differences in heart rate (HR) or "additional" HR reactions, so the anticipated decline in cardiac sympathetic response with age was not observed. The mechanisms underlying age-related reactions to mental stress are discussed. PMID- 2323328 TI - Aerobics enhances cardiovascular fitness and agility in preschoolers. AB - Investigated effects of aerobic exercise on a sample of 24 preschoolers. Thirty minutes of aerobic exercises were provided daily for a period of 8 weeks for a group of 12 children while the remaining 12 children engaged in freeplay on the school playground. The children were given pretests and posttests on the following measures: a submaximal exercise test on a pediatric bicycle (baseline and three workloads), an agility test, a health knowledge test, a self-esteem scale, and an observational measure of their gross-motor activity. Despite comparability on pretests, significant group X repeated measures effects suggested that the aerobic exercise group showed decreases in heart rate at all three workloads as well as increases in agility and self-esteem following the exercise program. These findings suggest that cardiovascular fitness, agility, and self-esteem can be facilitated in preschoolers by an aerobic exercise program. PMID- 2323327 TI - Cardiovascular and testosterone responses to contested dominance in women. AB - Examined cardiovascular and testosterone responses of dominant and submissive women to an acute stressor involving contested dominance. Twenty (10 dominant, 10 submissive) university students rated their dominance to a predefined reference group, participated in a task that involved debating with a trained technician, and were continuously provided with bogus feedback throughout the task concerning biochemical substances in their blood that purportedly covaried with dominance. Covariance analyses revealed that dominant women were much more reactive to the stressor in several cardiovascular parameters than those classified as submissive. Serum testosterone did not vary as a function of the experimental manipulation, and at each measurement point, dominant and submissive subjects had essentially identical serum levels of this hormone. Interestingly, however, baseline testosterone for the dominant group was related to changes in systolic blood pressure (i.e., gain scores computed as task response minus baseline values). PMID- 2323329 TI - Negative affectivity and the reporting of stressful life events. AB - Maddi, Bartone, and Puccetti (1987) and Schroeder and Costa (1984) reported inconsistent findings regarding the impact of negative affectivity (NA; i.e., neuroticism) contaminated life event items on observed life event-illness relationships. Here, unlike the previous studied, such contaminated items were nonjudgmentally identified. Among a sample of managers and professionals, it was found that NA-contaminated items correlated significantly with three measures of well-being (depression, life satisfaction, and physical symptoms) and that uncontaminated items were unassociated with the well-being indicators. Moreover, in two of three cases, the correlations between contaminated items and the well being measures were significantly different from the correlations between uncontaminated items and the well-being indicators. Therefore, we concluded that prior life event-well-being findings are inflated considerably by the use of NA contaminated events. Suggestions for future life events research that incorporate the NA construct are detailed. PMID- 2323330 TI - Exercise self-schemata: cognitive and behavioral correlates. AB - Presents two studies exploring the links between self-schemata and exercise behavior. Study 1 was designed to study information processing in individuals with exercise self-schemata. Study 2 was designed to assess, in a prospective design, the relationship between exercise self-schema and subsequent exercise behavior. The results revealed that individuals with exercise self-schemata (a) endorsed as self-descriptive more words and phrases related to exercising and fewer related to not exercising, (b) tended to take less time to make schema consistent judgments, (c) recalled more specific instances of past exerciser behavior and fewer specific instances of nonexerciser behavior, and (d) predicted that they were more likely to engage in future pro-exercise behavior. Moreover, individuals who thought of themselves as exercisers were more likely to report that they had adopted an exercise program than were individuals without such a self-schema. PMID- 2323331 TI - Assessing problems of cancer patients: psychometric properties of the cancer inventory of problem situations. AB - Evaluated the psychometric properties of the Cancer Inventory of Problem Situations (CIPS), a cancer-specific survey instrument designed to assess day-to day problems and rehabilitation needs of cancer patients. A heterogeneous group of 479 cancer patients participated in the research. The substructure of the CIPS was investigated using factor-analytic techniques. The CIPS was factored into 31 clinically useful subscales. Further analyses led to five higher order factors representing the physical, psychosocial, medical interaction, marital, and sexual problem areas characteristic of cancer and its treatment. Internal consistency of all the scales was high (mean alpha = .81). The test-retest reliability and validity of the instrument were also studied in a sample of 120 patients. Analyses of items, subscales, higher order factors, and total CIPS scores suggest excellent reliability. The pattern of correlations of the CIPS with other measures (psychological distress; physical, marital, and sexual functioning; and quality of life) provided preliminary evidence of concurrent, discriminant, and convergent validity. The CIPS appears to have sound psychometric properties and fills an important gap in the assessment of cancer patients for both clinical and research purposes. PMID- 2323332 TI - Telomere interactions may condition the programming of antigen expression in Trypanosoma brucei. AB - The AnTat 1.1 antigen type typically occurs late in a chronic infection by the EATRO 1125 stock of Trypanosoma brucei. The AnTat 1.1 gene, which is located 24 kb from a chromosome end, seems exclusively expressed by acting as a donor in gene conversion events targeted to the telomeric expression site. We report that this gene is sufficiently provided with the homology blocks required for recombination with the expression site, and is not interrupted by stop codons up to the 3' block of homology. A possible reason for its low probability of activation is an inverse orientation with respect to the proximal chromosome end, since, if correctly positioned, it is readily expressed at an early stage of infection, following gene conversion. This suggests that interactions between chromosome ends may precede and favour the rearrangements leading to antigenic variation. PMID- 2323333 TI - Positive and negative functional interactions between promoter elements from different classes of RNA polymerase III-transcribed genes. AB - Consensus tRNA gene promoter elements, A and B boxes, were introduced into the coding sequence of a Xenopus U6 gene. Combinations in which A and B boxes were coupled to wild-type or mutant U6 promoters were made. In this way information about both the functions of individual promoter elements and functional relationships between different classes of RNA polymerase III promoter element were obtained. Mutants in which the U6 PSE was non-functional were rescued by the presence of a B box, indicating a degree of functional relationship between these two elements. Moreover, the B box acted to increase the transcriptional activity and competitive strength of the wild-type U6 promoter. In contrast, no evidence was obtained to suggest that a tRNA A box can interact productively with U6 promoter elements in the absence of a B box. Data obtained suggest that the U6 PSE functions as an 'adaptor', being necessary to enable the basal U6 promoter to respond to upstream enhancement. Certain combinations of U6 and tRNA promoter elements are shown to be mutually antagonistic by a mechanism which is likely to involve blockage of transcription initiation. In summary, the U6 and tRNA promoters are shown to consist of functionally related, but distinct, promoter elements whose interactions shed new light on their normal roles in transcription. PMID- 2323334 TI - Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonic stem cells. AB - We have recently identified an enhancer, termed GPEI, in the 5'-flanking region of the rat glutathione transferase P gene, that is composed of two imperfect TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive elements (TREs). Unlike other TRE-containing enhancers, GPEI exhibits a strong transcriptional enhancing activity in F9 embryonic stem cells. Mutational analyses have revealed that the high activity of GPEI is mediated by two imperfect TREs. Each TRE-like sequence has no activity by itself but acts synergistically to form a strong enhancer which is active even in the very low level of AP-1 activity in F9 cells. Furthermore, we show that synthetic DNAs containing two perfect TREs in certain arrangements have strong transcriptional enhancing activities in F9 cells and the activity is greatly influenced by the relative orientation and the distance of two TREs. PMID- 2323335 TI - Malignant transformation of immortalized transgenic hepatocytes after transfection with hepatitis B virus DNA. AB - Persistent infection by hepatitis B virus (HBV) is epidemiologically correlated with the prevalence of hepatocellular carcinoma, but its role in tumor development is not yet understood. To study the putative oncogenic potential of HBV, a non-malignant immortal mouse hepatocyte line FMH202 harboring metallothionein promoter-driven simian virus 40 large tumor antigen was transfected with HBV DNA. All stably transfected clones which replicated HBV displayed malignant growth characteristics in soft agar and were tumorigenic upon inoculation in nude mice. The nude mice tumors were histologically classified as differentiated or anaplastic hepatocellular carcinomas. As with human liver carcinomas, rearrangements of in vitro integrated HBV sequences were observed in the nude mouse tumors, and in tumor-derived cell lines. In one case, expression of viral core and surface antigens was blocked in the tumors, correlating with hypermethylation of the HBV genome. However, the expression of X gene was maintained in most tumors and tumor-derived cell lines. X protein was detected in nuclei by immune fluorescence and by immune blot. These results provide the first demonstration that HBV displays oncogenic potential in an experimental system. This system could be useful to functionally identify HBV genes which convey a tumorigenic phenotype. PMID- 2323336 TI - Inactivation of the HIV LTR by DNA CpG methylation: evidence for a role in latency. AB - Infection of cells by HIV can result in a period of quiescence or latency which may be obviated by treatment with inducing agents such as 5-azacytidine. Evidence from these experiments demonstrate the existence of two CpG sites in the HIV LTR which can silence transcription of both reporter genes (CAT) and infectious proviral DNA when enzymatically methylated. This transcriptional block was consistently overcome by the presence of the trans-activator tat without significant demethylation of the HIV LTR. These results suggest that DNA hypermethylation of the HIV LTR may change the binding characteristics between LTR sequences and cellular proteins, thereby suppressing HIV LTR transcription and modulating viral expression. PMID- 2323337 TI - Establishment of the Deformed expression stripe requires the combinatorial action of coordinate, gap and pair-rule proteins. AB - In Drosophila embryos, anterior-posterior positional identities are set and maintained by the expression boundaries of homeotic selector genes. The establishment of the initial expression boundaries of the homeotic genes are in turn dependent on earlier acting patterning genes of Drosophila. To define the combinations of early genes that are required to establish a unique blastoderm stripe of expression of the homeotic gene Deformed, we have analysed single and double patterning mutants and heat shock promoter fusion constructs that ectopically express early acting regulators. We find that the activation of Deformed is dependent on combinatorial input from at least three levels of the early hierarchy. The simplest activation code sufficient to establish Deformed expression, given the absence of negative regulators such as fushi-tarazu, consists of a moderate level of expression from the coordinate gene bicoid, in combination with expression from both the gap gene hunchback, and the pair-rule gene even-skipped. In addition, the activation code for Deformed is redundant; other pair-rule genes in addition to even-skipped can apparently act in combination with bicoid and hunchback to activate Deformed. PMID- 2323338 TI - Repetitive sequence involvement in the duplication and divergence of mouse lysozyme genes. AB - Mouse M and P lysozymes are the products of separate genes, are specifically expressed in separate tissues, and are adapted to different functions. The lysozyme genes have assumed these markedly different characteristics following their generation by gene duplication 30-50 million years ago. The discovery of the lysozyme P gene only 5 kb upstream from the M gene in tandem repeat has enabled an investigation of the molecular basis of their duplication and subsequent divergence. The duplication is shown to have involved recombination between two B2 repeat sequences flanking the original gene. The resulting downstream copy has retained the myeloid specificity of expression along with just 1.7 kb of upstream sequences, while the upstream copy is inactive in macrophages and has become expressed instead in the small intestine. Although multiple gene conversion events have served to maintain a generally high homology between the genes, certain regions have been found to be specific for either one of the gene pair: two repetitive sequences peculiar to the P region may serve to protect the coding regions from gene conversion, while sequences unique to the M gene may be more directly involved in differential regulation. PMID- 2323339 TI - Electron microscopy mapping of pBR322 DNA curvature. Comparison with theoretical models. AB - A map of local curvature of the pBR322 DNA has been established by electron microscopy analysis of linearized plasmid molecules. To determine their polarity these molecules are one end labelled with an avidin-ferritin-biotin complex and the images are digitized. Local curvature is calculated from two mathematical treatments of the DNA trajectory and expressed in term of a mean dinucleotide wedge angle. Eight regions of curvature are distinguished. The four main regions of curvature have a high content of phased AA runs. The experimental curvature map is compared to theoretical maps of curvature obtained from four available models for DNA curvature. PMID- 2323340 TI - An upstream transcription factor, USF (MLTF), facilitates the formation of preinitiation complexes during in vitro chromatin assembly. AB - During in vitro chromatin assembly the formation of transcription complexes is in direct competition with the assembly of promoter sequences into nucleosomes. Under these conditions the fold stimulation of transcription by an upstream transcription factor (USF) was greater than that observed in the absence of nucleosome assembly. Function of USF during nucleosome assembly required the simultaneous presence of the TATA box binding protein TFIID. Unlike TFIID, USF alone was unable to prevent repression of the promoter during nucleosome assembly. Furthermore, USF displayed reduced or no transcriptional stimulatory activity when added to previously assembled minichromosomes. Under conditions of nucleosome assembly, USF increased the number of assembled minichromosomes which contained stable preinitiation complexes. Subsequent to assembly, the rate at which preformed complexes initiated transcription appeared to be independent of the presence of USF. Thus USF potentiated the subsequent transcriptional activity of the promoter indirectly, apparently by increasing the rate or stability of TFIID binding. This activity resulted in the promoter becoming resistant to nucleosome mediated repression. These observations suggest that some ubiquitous upstream factors, e.g. USF, may play an important role in establishing the transcriptional potential of cellular genes during chromatin assembly. PMID- 2323341 TI - Nucleosome assembly in vitro: separate histone transfer and synergistic interaction of native histone complexes purified from nuclei of Xenopus laevis oocytes. AB - High speed supernatants of Xenopus laevis oocyte nuclei efficiently assemble DNA into nucleosomes in vitro under physiological salt conditions. The assembly activity cofractionates with two histone complexes composed of the acidic protein N1/N2 in complex with histones H3 and H4, and nucleoplasmin in complex with histones H2B and H2A. Both histone complexes have been purified and their nucleosome assembly activities have been analysed separately and in combination. While the histones from the N1/N2 complexes are efficiently transferred to DNA and induce supercoils into relaxed circular plasmid DNA, the nucleoplasmin complexes show no supercoil induction, but can also transfer their histones to DNA. In combination, the complexes act synergistically in supercoil induction thereby increasing the velocity and the number of supercoils induced. Electron microscopic analysis of the reaction products shows fully packaged nucleoprotein structures with the typical nucleosomal appearance resulting in a compaction ratio of 2.8 under low ionic strength conditions. The high mobility group protein HMG-1, which is also present in the soluble nuclear homogenate from X. laevis oocytes, is not required for nucleosome core assembly. Fractionation experiments show that the synergistic effect in the supercoiling reaction can be exerted by histones H3 and H4 bound to DNA and the nucleoplasmin complexes alone. This indicates that it is not the synchronous action of both complexes which is required for nucleosome assembly, but that their cooperative action can be resolved into two steps: deposition of H3 and H4 from the N1/N2 complexes onto the DNA and completion of nucleosome core formation by addition of H2B and H2A from the nucleoplasmin complexes. PMID- 2323342 TI - Periodicity of DNA folding in higher order chromatin structures. AB - Each level of DNA folding in cells corresponds to a distinct chromatin structure. The basic chromatin units, nucleosomes, are arranged into solenoids which form chromatin loops. To characterize better the loop organization of chromatin we have assumed that the accessibility of DNA inside these structures is lower than on the outside and examined the size distribution of high mol. wt DNA fragments obtained from cells and isolated nuclei after digestion with endogenous nuclease or topoisomerase II. The largest discrete fragments obtained contain 300 kbp of DNA. Their further degradation proceeds through another discrete size step of 50 kbp. This suggests that chromatin loops contain approximately 50 kbp of DNA and that they are grouped into hexameric rosettes at the next higher level of chromatin structure. Based upon these observations a model by which the 30 nm chromatin fibre can be folded up into compact metaphase chromosomes is also described. PMID- 2323343 TI - Crystal structure of a berenil-dodecanucleotide complex: the role of water in sequence-specific ligand binding. AB - The three-dimensional structure of a complex between the dodecanucleotide d(CGCGAATTCGCG) and the anti-trypanocidal drug berenil, has been determined to a resolution of 2.5 A. The structure has been solved by molecular replacement and refined to an R factor of 0.177. A total of 49 water molecules have been located. The drug is bound at the 5'-AAT-3' region of the oligonucleotide. At one end of the drug the amidinium group is in hydrogen-bonded contact with N3 of the adenine base complementary to the thymine of the AAT. The other amidinium group does not make direct interactions with the DNA. Instead, a water molecule mediates between them. This is in hydrogen-bonded contact with an amidinium nitrogen atom, N3 of the 5' end adenine base and the ring oxygen atom of an adjacent deoxyribose. Molecular mechanics calculations have been performed on this complex, with the drug at various positions along the sequence. These show that the observed position is only 0.8 kcal/mol higher in energy than the best position. It is suggested that there is a broad energy well in the AATT region for this drug, and that water molecules as well as the neighbouring sequence, will determine precise positioning. More general aspects of minor groove binding are discussed. PMID- 2323344 TI - Vascular effects of topically applied bradykinin on the human nasal mucosa. AB - To evaluate the vascular effects of topically applied bradykinin on the human nasal mucosa, 13 asymptomatic hay fever patients and 11 non-allergic subjects were challenged with diluent or bradykinin in three increasing doses. Mucosal blood flow was determined with the 133Xenon wash-out method and expiratory peak flow measurements used to assess nasal airway resistance before and after challenge. Nasal symptoms were recorded. Nasal secretion quantity was measured from preweighed paper handkerchiefs. Bradykinin induced a slight increase in nasal airway resistance which was similar in both allergic and non-allergic subjects. Nasal secretion was clearly increased after challenge with bradykinin compared with challenge with diluent in both allergic and non-allergic subjects. Bradykinin did not, however, induce any change in mucosal blood flow in either group. The present findings could be explained by direct effects of bradykinin on the vascular bed without reflex activity. Bradykinin would then induce an increase in vascular permeability with subsequent oedema formation and increased amounts of fluid on the mucosal surface. In contrast to allergen challenge, bradykinin challenge had no effect on the resistance vessels, changes of which had previously been shown to be largely reflex-mediated. PMID- 2323346 TI - Behavioural effects and supersensitivity in the rat following intranigral MPTP and MPP+ administration. AB - Unilateral intranigral injections of MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) and MPP+ (1-methyl-4-phenylpyridine) were given to young rats and unilateral intranigral injections of MPTP were given to old rats. MPTP in old rats and MPP+ in young rats induced ipsiversive circling for at least one week after injection and contraversive circling after the systemic administration of apomorphine; the number of D-2 receptors (Bmax) in the striatum of the injected hemisphere increased compared with that of control rats. MPTP in young rats induced only short-lasting ipsiversive circling and no contraversive circling after apomorphine; the number of striatal D-2 receptors did not increase. These results suggest that the neurotoxicity of MPTP is age-dependent in the rat, and that MPTP has neurotoxic effects on the nigrostriatal dopaminergic system in old rats and induces dopamine receptor supersensitivity in the denervated striatum. PMID- 2323345 TI - Comparison of neuromedin-N and neurotensin on net fluid flux across rat small intestine. AB - Neuromedin-N, a hexapeptide recently isolated and purified from porcine spinal cord, has close sequence homology with the C-terminal region of the tridecapeptide neurotensin. Both peptides have a remarkably similar peripheral distribution. Little is known of the biological activity of neuromedin-N. Neurotensin and peptide histidine methionine are known to stimulate net fluid secretion into rat small intestine. We have therefore tested the effect of neuromedin-N and the hexapeptide neurotensin-(8-13), the smallest fully active analogue of neurotensin in this system, compared with that of neurotensin and peptide histidine methionine. All four peptides reduced net absorption in low doses and caused net secretion in larger doses. However, whereas peptide histidine methionine was active in all areas of the small intestine, neurotensin, neurotensin-(8-13) and neuromedin-N were inactive in the duodenum. In the post duodenal areas neurotensin was approximately 7 times more active than peptide histidine methionine, 21 times more potent than neuromedin-N and 33 times more potent than neurotensin-(8-13). PMID- 2323347 TI - Effects of buflomedil and its two derivatives, CRL40634 and CRL40598, on pancreatic exocrine secretion in the rat. AB - Buflomedil is a vasoactive drug used in the treatment of peripheral vascular disease, and seems to be an antagonist of both alpha 1- and alpha 2-vascular adrenoceptors. CRL40634 and CRL40598 are metabolites of buflomedil and also possess vasoactive properties. The purpose of this study was to investigate whether buflomedil, CRL40634 and CRL40598 have antagonist activity on the alpha 2 adrenoceptors involved in the inhibition of exocrine pancreatic secretion. In acute pancreatic fistula rats, buflomedil, CRL40634 and CRL40598 did not suppress the inhibitory effect of clonidine against 2-deoxy-glucose-induced pancreatic secretion. However, all three drugs inhibited 2-deoxy-glucose-induced pancreatic secretion, their order of potency being CRL40598 greater than CRL40634 greater than buflomedil. PMID- 2323348 TI - Contribution of baroreceptor reflexes to blood pressure and sympathetic responses to cholecystokinin and vasoactive intestinal peptide in anesthetized dogs. AB - The effects of synthetic vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) on systemic blood pressure and renal nerve activity were studied before and after cervical vagotomy, and sino-aortic denervation with vagotomy in anesthetized dogs. Intravenous injection of VIP (5 micrograms/kg) in animals with an intact neuraxis produced a significant decrease in systemic blood pressure and a significant increase in renal nerve activity. These responses to VIP did not change after vagotomy and after complete denervation, VIP did not cause any change in renal nerve activity, even during hypotension. The level of hypotension after complete denervation was greater than that under other conditions. These results indicate that the cardiovascular effects of VIP are reduced by activation of the systemic baroreceptors. Intravenous injection of CCK (10 micrograms/kg) in animals with an intact neuraxis produced significant decreases in blood pressure and renal nerve activity. These responses to CCK were abolished in animals with cervical vagotomy only. However, following complete denervation of the carotid sinus and total section of the vagal nerves, CCK caused a significant increase in blood pressure and renal sympathetic nerve activity. These results indicate that the sympathetic depressor effect of CCK may be mediated by activation of the vagal afferents, and that the sympathetic pressor effect may be due to a direct action of CCK on the central nervous system. Thus, each gastrointestinal peptide may regulate the cardiovascular system through a different mechanism. PMID- 2323349 TI - Cardiovascular effects of neurotensin and some analogues on rats. AB - When administered in vivo into the femoral vein of normotensive rats, neurotensin, neurotensin-(8-13), and [D-Lys8]neurotensin-(8-13) decreased diastolic blood pressure in a dose-dependent manner, without change in heart rate. All three peptides evoked tachyphylaxis and a triphasic depressor-pressor depressor, response at higher doses. The rank order of potency was neurotensin greater than [D-Lys8]neurotensin-(8-13) greater than neurotensin-(8-13). In organ chamber experiments, both neurotensin and neurotensin-(8-13) at a range of concentrations which induced dose-dependent decreases in blood pressure, did not significantly change tension in rat aorta rings with or without endothelium. In contrast, [D-Lys8]neurotensin-(8-13) induced weak dose-dependent relaxation of both rings with or without endothelium. However, this effect was not obtained at concentrations able to decrease the blood pressure. Indomethacin did not change the vasodilator effect of [D-Lys8]neurotensin-(8-13). There was no correlation between the vasodilator effect of this peptide and its ability to decrease blood pressure. These experiments suggest that the hypotension was not due to a direct vasodilator effect on the smooth muscle. In addition, since the rank order of peptide potency was opposite of those found in previous studies of second messenger synthesis and binding to neural tissue, these data suggest that there is a second receptor for neurotensin or that neurotensin can also bind to a different unknown receptor. PMID- 2323350 TI - Interaction between halothane and morphine on isolated heart muscle. AB - The present study describes the effects of halothane on morphine activity in the isolated left atria of the rat. Concentration-response curves were obtained for the negative inotropic effects of morphine on electrically stimulated left atria. Morphine significantly decreased the contractile force, with an inhibitory concentration 16 (IC16) of 3.130.698 +/- 22.5 X 10(-9) M. The opiate agonist was more potent in reserpinized rats, causing a consistent negative inotropic action over a wide range (10(-8)-10(-4) M) or morphine concentrations. The IC16 of morphine was significantly (P less than 0.001) decreased in the presence of 1.5% v/v halothane. The administration of L-naloxone (3 X 10(-7)-10(-6) M) but not D naloxone (10(-6) M) antagonized the inhibitory effects of morphine in the presence of halothane. These results demonstrate that halothane increases the potency of morphine on the isolated left atria and suggest that this effect is mediated by opioid receptors. PMID- 2323351 TI - Naloxone-insensitive modulation of gastric acid output by [D Met2,Pro5]enkephalinamide in rats. AB - Studies from our laboratory have previously shown that two opioid agonists (morphine and [D-Met2,Pro5]enkephalinamide) aggravate, whereas naloxone inhibits cold-restraint stress-induced ulceration in rats. In the present study the effects of these substances were examined using the Shay-model. Contrary to expectations, both naloxone and the opioid agonists decreased gastric acid output. Naloxone in combination with either opioid agonist failed to reverse their inhibitory action. Thus the secretory activity of the stomach may be modulated by opioids in both naloxone-reversible and irreversible ways. PMID- 2323352 TI - Effects of [1-desamino-8-D-arginine]vasopressin and papaverine on rabbit renal pelvis. AB - The effects of [1-desamino-8-D-arginine]vasopressin (DDAVP) (V2 receptor agonist) and papaverine on four continuous circular smooth muscle strips in rabbit renal pelvis were studied by an isometric tension recording methods. DDAVP suppressed spontaneous contractions in a dose-dependent and region-dependent way. Papaverine suppressed these contractions in a dose-dependent way simultaneously in all four portions. These results suggest that there may be distribution differences of V2 receptors in the renal pelvis. Together with its anti-diuretic action, DDAVP may merit consideration for the treatment of renal colic. PMID- 2323353 TI - Dopamine D-2 receptors imaged by PET in Cebus apella using [18F]benzamide neuroleptic. PMID- 2323354 TI - Two outbreaks of Legionnaires' disease in Bolton Health District. AB - In 1988, there were two outbreaks of legionellosis in Bolton Health District. Altogether 37 cases of Legionnaires' disease and 23 cases of non-pneumonic legionellosis were identified. Twenty-five patients with Legionnaires' disease were associated with an engineering plant, 4 with Bolton town centre, and 8 with both the plant and town centre. Twenty-two people with non-pneumonic legionellosis were linked with the engineering plant and one with the plant and the town centre. A case-control study carried out among 37 employees with legionellosis and 109 control subjects at the plant showed that infection was associated with one of the 15 cooling towers on the site. Legionella pneumophila indistinguishable by serological and genetic typing methods was isolated from this cooling tower and from sputum samples from two patients. In the town centre, no one tower was linked with infection and L. pneumophila was not cultured from any of the nine towers identified. Control measures were implemented and to date there have been no further cases of legionellosis associated with Bolton Health District. PMID- 2323355 TI - Secretor status, smoking and carriage of Neisseria meningitidis. AB - A survey of ABO blood groups, secretor status and smoking habits among 389 students and staff of a school in which there was an outbreak of meningococcal disease found no difference in the distribution of the ABO blood groups but a significantly higher proportion of non-secretors (37.6%) in the population examined compared with that reported for previous surveys of the neighbouring population in Glasgow (26.2%) (P less than 0.0005). There was also a significantly higher proportion of non-secretors among carriers of meningococci (47%) compared with non-carriers (32%). Increased carriage of meningococci among non-secretors might contribute to the increased susceptibility of individuals with this genetic characteristic to meningococcal disease observed in previous studies. Although passive exposure to cigarette smoke has been associated with meningococcal disease, there was no association between passive smoking and carriage. There was, however, a significant association between active smoking and carriage. PMID- 2323356 TI - An outbreak of Salmonella saint-paul infection associated with beansprouts. AB - In March 1988, there was an outbreak of infection by a strain of Salmonella saint paul with a distinctive antigenic marker. A total of 143 reports were received between 1 March and 7 June. Preliminary investigations suggested that raw beansprouts were a possible source of infection and a case-control study confirmed the association. S. saint-paul of the epidemic type was isolated from samples of beansprouts on retail sale in different cities in the United Kingdom and from mung bean seeds on the premises of the producer who was most strongly associated with cases. In addition, Salmonella virchow PT34 was isolated from samples of raw beansprouts and was subsequently associated with seven cases of infection. Four other serotypes of salmonella were also isolated from beansprouts. On 8 April the public were advised to boil beansprouts for 15 seconds before consumption, and the premises of the one producer associated with many cases were closed. As a result of these actions there was a significant decrease in the number of infections with S. saint-paul. PMID- 2323357 TI - A comparative study of the heat resistance of salmonellas in homogenized whole egg, egg yolk or albumen. AB - Salmonella enteritidis PT4 was found to be more resistant to heat in egg than some other common egg-associated salmonellas. This organism was significantly more heat sensitive than S. senftenberg 775W, however, and should not survive in pasteurized liquid egg. PMID- 2323358 TI - Environmental sanitation, food and water contamination and diarrhoea in rural Bangladesh. AB - This study examined the role of food and water contamination in a health impact evaluation of a water and sanitation intervention project. Although lower diarrhoea rates were found in the improved area no consistent difference in food and water contamination was observed between areas. Furthermore, no relationship was found between contamination and diarrhoea in either area, even after controlling for the nutritional status of children. These results imply that other vehicles of transmission might be more important than food and water in diarrhoeal transmission. The focus of interventions should therefore be on changing behaviours to improve overall hygiene. PMID- 2323359 TI - Intestinal spirochaetes in a Gulf Arab population. AB - Spirochaetal bacteria were isolated from the faeces of 11.4% of 1000 hospital patients and 26.7% of 292 healthy local nationals in the Muscat area of the Sultanate of Oman. A case-control study of patient records showed the isolation of the spirochaete to be associated with Omani nationality, age in excess of 2 years and attendance at self-referral health-care facilities. No association was found with symptomatic intestinal disease or microscopic abnormalities of the stool. PMID- 2323360 TI - Vaccine prophylaxis of abattoir-associated Q fever: eight years' experience in Australian abattoirs. AB - During the period 1981-8 a clinical trial of a Q fever vaccine (Q-vax; Commonwealth Serum Laboratories, Melbourne) has been conducted in abattoir workers and other at-risk groups in South Australia. Volunteers in four abattoirs and visitors to the abattoirs were given one subcutaneous dose of 30 micrograms of a formalin-inactivated, highly-purified Coxiella burnetii cells, Henzerling strain, Phase 1 antigenic state, in a volume of 0.5 ml. During the period, over 4000 subjects have been vaccinated and the programme continues in the abattoirs and related groups. 'Common' reactions to the vaccine comprised tenderness and erythema, rarely oedema at the inoculation site and sometimes transient headache. Two more serious 'uncommon' reactions, immune abscess at the inoculation site, were observed in two subjects, and two others developed small subcutaneous lumps which gradually dispersed without intervention. Protective efficacy of the vaccine appeared to be absolute and to last for 5 years at least. Eight Q fever cases were observed in vaccinees, but all were in persons vaccinated during the incubation period of a natural attack of Q fever before vaccine-induced immunity had had time (greater than or equal to 13 days after vaccination) to develop. On the other hand, 97 Q fever cases were detected in persons working in, or visiting the same abattoir environments. Assays for antibody and cellular immunity showed an 80-82% seroconversion after vaccination, mostly IgM antibody to Phase 2 antigen, in the 3 months after vaccination. This fell to about 60%, mostly IgG antibody to Phase 1 antigen, after 20 months. On the other hand, 85-95% of vaccinees developed markers of cell mediated immunity as judged by lymphoproliferative responses with C. burnetii antigens; these rates remained elevated for at least 5 years. The Q fever vaccine, unlike other killed rickettsial vaccines, has the property of stimulating long-lasting T lymphocyte memory and this may account for its unusual protective efficacy as a killed vaccine. PMID- 2323361 TI - Serologically proven acute rubella infection in patients with clinical diagnosis of dengue. AB - Patients with a clinical diagnosis of dengue but negative by serological testing were studied for rubella infection. Paired sera were obtained from 69 patients during an outbreak in Yucatan, Mexico. The presence of specific anti-viral IgM in the acute sera was considered as diagnostic for rubella infection. The immunoglobulin was determined by measuring the difference in the inhibition of hemagglutination between the non-reduced and the reduced fractionated sera. Immunoglobulins were separated by sucrose density centrifugation. Acute rubella infection was found in 7 (10.1%) of the patients. These results demonstrate active rubella infection in patients clinically diagnosed as dengue. PMID- 2323362 TI - Modulation of tartrate-resistant acid phosphatase expression by calcitriol in CSF induced macrophage colonies. AB - The osteoclast is thought to be a hemopoietically derived cell, but questions exist about which hemopoietic growth factors are responsible for proliferation of osteoclast precursors. Experiments were thus performed to see if recombinant human colony-stimulating factors (CSFs) influenced the expression of tartrate resistant acid phosphatase (TRAP), an osteoclast marker enzyme, by monkey bone marrow colonies in vitro. In addition, the effect of 1,25-dihydroxyvitamin D3 (calcitriol) on CSF-induced colony growth and TRAP expression was also determined. Bone marrow was obtained from a single Macaca nemestrina monkey, kept frozen in liquid nitrogen, and aliquots of frozen cells were thawed and placed at 10(5) cells per plate in a standard cell colony-forming unit (CFU-C) assay. The recombinant human CSFs (granulocyte-macrophage CSF, GM-CSF; macrophage CSF, M CSF; interleukin 3, IL-3; and granulocyte CSF, G-CSF) were added to the cultures at 50 U/ml, and calcitriol was titrated for each CSF from 0.1 to 100 nM. Day-14 colonies were stained to demonstrate TRAP-positive cells in individual colonies. GM-CSF caused an increase (193%, p less than 0.0004) in total colony numbers that was only partially inhibited by calcitriol. IL-3 and M-CSF had less effect, and G CSF had no effect. GM-CSF also caused a large increase in TRAP-positive macrophage (M) colonies (326%, p less than 0.0001) and changed the relative proportion of TRAP-positive M colonies from 39% to 62% of all M colonies. M-CSF caused less increase in numbers of TRAP-positive M colonies and had no effect on the proportion of TRAP-positive colonies. When GM-CSF was present, calcitriol caused a maximum number of TRAP-positive colonies to appear at 1 nM, and it caused a drastic decrease in TRAP-positive colonies at higher doses. Calcitriol at 10 nM caused TRAP-negative colonies to increase in number and proportion when GM-CSF was present, but in the presence of M-CSF, the same dose of calcitriol caused a decline in numbers of TRAP-negative colonies. These results suggest that GM-CSF may be important in the replication of TRAP-positive mononuclear cells that resemble osteoclast precursors and that myeloid cell development may be weighted toward TRAP-positive or TRAP-negative progeny depending on whether GM CSF or M-CSF predominates. They further suggest that calcitriol concentration may be critical in this process. PMID- 2323364 TI - Relationship between cells forming colonies in diffusion chambers in vivo (CFU-D) and cells with high proliferative potential in vitro (HPP-CFC-1 and -2). AB - In vivo diffusion chambers implanted in normal mice after 5 days of bone marrow cell culture contained precursor cells that in the presence of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), interleukin 3 (IL-3), or colony-stimulating factor 1 (CSF-1), alone or in combination, formed both small and large (high proliferative potential colony-forming cells, HPP-CFC) macrophage-containing colonies in vitro. Synergistic factor from serum-free 5637 cell-conditioned medium (SF5637) enhanced HPP-CFC colony growth only in cultures containing CSF-1. Higher numbers of CSF-1- plus IL-3-responsive colony-forming cells (HPP-CFC-2) were detected in diffusion chamber colony-forming unit (CFU-D) colonies than in intercolony areas, suggesting that they were derived from cells that give rise to the diffusion chamber colony. Further study demonstrated that CFU-D colonies contained cells that formed large macrophage-containing colonies (HPP-CFC-1) in CSF-1- plus SF5637-containing cultures. These findings suggest that single cells (CFU-D) forming colonies in diffusion chambers in mice can give rise to both HPP-CFC-1 and to cells probably representing their progeny, HPP-CFC 2. PMID- 2323363 TI - Purification of peripheral blood hematopoietic cells using Campath-1M monoclonal antibody. AB - The purpose of this study was to develop a method for exhaustive depletion of T cells in preparation for allogeneic peripheral blood (PB) hematopoietic stem cell (HSC) transplantation. Our goal was to achieve 4 logs of T-cell reduction while minimizing the loss of colony-forming progenitor cells. Campath-1M, a rat IgM cytolytic to T cells, B cells, and monocytes in the presence of human complement, was chosen for the investigation. To determine the best target population for Campath treatment, three different PB mononuclear cell (MNC) populations were examined: 1) total MNC isolated with Ficoll-sodium diatrizoate; 2) MNC after T cell depletion by sheep red blood cell rosetting and high capacity Percoll density gradient fractionation (E-MNC); and 3) B/Null cells, a population of E MNC obtained by lysing monocytes with L-phenylalanine methyl ester (PME). Of the three target MNC populations, Campath-treated B/Null cells had the highest cloning efficiencies (CE) for granulocyte-macrophage colony-forming units (CFU GM) and erythroid burst-forming units (BFUe) (56.7 and 38.5 colonies per 5 x 10(3) cells, respectively) and the highest enrichments for CFU-GM (108.2-fold, range 18- to 440-fold) and BFUe (178.5-fold, range 78- to 314-fold). Recoveries of progenitor cells were comparable for Campath-treated MNC (49.7% and 84.5%, respectively, for CFU-GM and BFUe) and Campath-treated B/Null (44.8% and 76.1%), and significantly higher than those from Campath-treated E-MNC (19.5% and 34.3%). The T-cell content in the Campath-treated B/Null cells were reduced by 5.0 logs from the starting MNC, as determined by limiting dilution analysis (LDA). We conclude that Campath-1M can be used for T-cell depletion of PB HSC. The best results were obtained when T cells and monocytes were removed prior to Campath treatment. This cell population is highly enriched for hematopoietic cells and may prove useful for in vitro studies as well allogeneic transplantation. PMID- 2323365 TI - Chemotactic capabilities of HL-60 human myeloid leukemia cells differentiated to eosinophils. AB - HL-60 human myeloid leukemia cells can be induced to differentiate into cells with many of the morphological, biochemical, and functional features of mature neutrophils, monocyte/macrophages, and eosinophils. HL-60 neutrophils are known to respond to several chemotactic compounds, but similar data do not exist for HL 60 eosinophils. We studied the chemotactic capabilities of eosinophil differentiated HL-60 cells using a blind-well chamber technique. HL-60 eosinophils responded to the specific eosinophilotactic tetrapeptides Ala-Gly-Ser Glu, Val-Gly-Asp-Glu, and Val-Gly-Ser-Glu; to the formylated tripeptide N-formyl L-Met-L-Leu-L-Phe (fMLP); and to extracts estrogen-treated rat uteri, which contain an eosinophilotactin. Concentration optima for chemotaxis of HL-60 eosinophils were similar to those for normal human and rodent eosinophils. Neutrophil-differentiated HL-60 cells responded only to fMLP, whereas undifferentiated HL-60s showed no chemotactic ability. The time course of development of chemotactic competence paralleled other developmental changes in HL-60 eosinophilic differentiation, suggesting a common control mechanism. We conclude that the ability to respond to specific eosinophilotactic compounds is a feature of HL-60 cells that have differentiated to eosinophils and that this cell line may be used as a model system in studies of eosinophil chemotaxis. PMID- 2323366 TI - Early B-lymphocyte precursor cells in mouse bone marrow: subosteal localization of B220+ cells during postirradiation regeneration. AB - The localization of early B-lymphocyte precursor cells in the bone marrow of young mice has been studied during recovery from sublethal whole body gamma irradiation (150 rad). Initial studies by double immunofluorescence labeling of the B-lineage-associated cell surface glycoprotein, B220, and of mu heavy chains in bone marrow cell suspensions, demonstrated a sequential wave of regeneration of early B precursor cells, pre-B cells, and B cells. Early B precursor cells expressing B220 but not mu chains were enriched at 1-3 days following irradiation. After in vivo administration of 125I-labeled monoclonal antibody 14.8 to detect B220+ cells in situ, light and electron microscope radioautography of femoral bone marrow sections revealed concentrations of labeled B220+ cells located peripherally near the cortical bone at 1-3 days following irradiation, increasing in numbers in more central areas by 5-7 days. Proliferative B220+ precursor cells were found within layers of bone-lining cells and in a subosteal area characterized by a prominent electron-dense extracellular matrix, often associated with stromal reticular cells. The results demonstrate that the precursor cells that are active in the bone marrow early in the recovery of B lymphopoiesis after gamma-irradiation are located both within and near the endosteum of the surrounding bone. The distinctive extracellular matrix and stromal cell associations noted in this region may contribute to a supportive local microenvironment for early hemopoietic progenitor cells. PMID- 2323368 TI - Glutathione: an in vitro granulopoiesis inhibitor at nanomolar concentration, isolated from calf spleen. AB - We isolated a peptide from calf spleen that specifically inhibits murine granulopoiesis in vitro. Human T-lymphocyte colony growth was not affected. Formation of erythroid colony-forming units (CFU-E) was only slightly inhibited at a concentration 1000-fold higher compared to granulocyte-macrophage colony forming cell (GM-CFC) assay. After high performance liquid chromatography purification we isolated a monomer (reduced peptide) showing the inhibitory activity and a dimer (oxidized peptide) with stimulatory activity. The isolated peptide was identified as glutathione. The reduced form of this well-known tripeptide (GSH) specifically inhibits murine granulopoiesis in vitro at 10(-7) 10(-8) M concentration. Oxidized glutathione (GSSG) stimulates GM-CFC formation; the extent of stimulation depends on the colony-stimulating factor concentration. The striking finding that GSH and GSSG modulate granulopoiesis at nanomolar concentrations requires further studies on the molecular interaction between either peptide with GM-CSF and its receptor protein. PMID- 2323367 TI - Tumor necrosis factor exerts dose-dependent effects on erythropoiesis and myelopoiesis in vivo. AB - Recombinant human tumor necrosis factor alpha (TNF) administered i.v. to Lewis rats as a daily low dose for 1 week induces an erythroid hyperplasia of late normoblasts. Although the erythroid marrow compartment is hyperplastic, the morphology of the normoblasts is dysplastic and there is no accompanying increase in circulating red blood cells, suggesting a state of ineffective erythropoiesis. TNF administered on the same daily schedule as a high dose induces an erythroid hypoplasia of late normoblasts and a peripheral anemia with decreases in the hematocrit and hemoglobin. A tremendous myeloid hyperplasia is noted in rats treated with high-dose TNF, and the mechanism of the erythroid anemia may be in part due to the increase in neutrophils. In support of the hypothesis that the erythroid anemia may be partly myelophthisic in nature, a decrease in marrow lymphocytes was also noted. On the other hand, the dysplastic morphology of the late erythroid precursors in rats treated with low-dose TNF would also be consistent with a destructive effect of TNF on erythroid precursors as a mechanism of TNF-related anemia. In light of the in vitro inhibitory effects of TNF on erythropoiesis and myelopoiesis as reported by previous investigators, the erythroid and myeloid hyperplasia noted in vivo most likely represent indirect effects. PMID- 2323369 TI - Dissecting the hematopoietic microenvironment. VI. The effects of several growth factors on the in vitro growth of murine bone marrow CFU-F. AB - The effects of several growth factors on the proliferation of fibroblastic colony forming units (CFU-F) were studied. In the present study CFU-F colonies were found to consist of fibroblasts, macrophages, and endothelial cells. Growth factors, including interleukin 3 (IL-3), interleukin 1 alpha (IL-1 alpha), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), macrophage colony-stimulating factor (M-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and buffalo rat liver cell conditioned medium (BRL-CM) were tested for stimulation of the proliferation of CFU-F in a standard culture in both 2% and 15% serum. Overall, the colony numbers produced in 15% serum were much higher than in 2% serum with or without growth factors. However, the influence of several growth factors on CFU-F cultured in 2% serum was relatively greater than in 15% serum when compared to controls. The stimulation of CFU-F by FGF only occurred in culture with 15% serum, and the stimulation by PDGF only occurred with 2% serum. Overall, the strongest stimulations were produced by PDGF, IL-3, and BRL-CM. Combining the other growth factors with IL-3, PDGF, or IL-1 alpha enhanced their effects only modestly. The stimulation by growth factors included increases of the cell numbers between and within colonies as well as an increase in the number of colonies. The study produced results that suggest a complex interaction mediated by growth factors between fibroblasts and other stromal cells within the CFU-F colonies and within the bone marrow itself. PMID- 2323370 TI - Dissecting the hematopoietic microenvironment. VII. The production of an autostimulatory factor as well as a CSF by unstimulated murine marrow fibroblasts. AB - Purified normal murine bone marrow-derived fibroblasts were shown to produce a factor that stimulates the in vitro growth of fibroblastic colony-forming unit (CFU-F) colonies. Conditioned medium from the purified fibroblasts (F-CM) also stimulated pure marrow fibroblasts themselves. Analysis of the F-CM detected the presence of macrophage colony-stimulating factor (M-CSF), and low levels of interleukin 1 (IL-1) and interleukin 6 (IL-6), but no detectable levels of interleukin 3 (IL-3), interleukin 5 (IL-5), granulocyte-macrophage colony stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF). Macrophages and endothelial cells, freed from other bone marrow components, required the F-CM if no other growth factors were added. We conclude that F-CM contains an autocrine factor, which the evidence suggests is IL-1, for bone marrow fibroblasts, and a paracrine factor (CSF-1) for macrophages and/or endothelial cells. PMID- 2323371 TI - Effects of lesions of the nucleus of the optic tract on optokinetic nystagmus and after-nystagmus in the monkey. AB - 1. The nucleus of the optic tract (NOT) and the dorsal terminal nucleus (DTN) of the accessory optic system were lesioned electrolytically or with kainic acid in rhesus monkeys. When lesions involved NOT and DTN, peak velocities of optokinetic nystagmus (OKN) with slow phases toward the side of the lesion were reduced, and optokinetic after-nystagmus (OKAN) was reduced or abolished. The jump in slow phase eye velocity at the onset of OKN was smaller in most animals, but was not lost. Initially, there was spontaneous nystagmus with contralateral slow phases. OKN and OKAN with contralateral slow phases were unaffected. 2. Damage to adjacent regions had no effect on OKN or OKAN with two exceptions: 1. A vascular lesion in the MRF, medial to NOT and adjacent to the central gray matter, caused a transient loss of the initial jump in OKN. The slow rise in slow phase velocity was prolonged, but the gain of OKAN was unaffected. There was no effect after a kainic acid lesion in this region in another animal. 2. Lesions of the fiber tract in the pulvinar that inputs to the brachium of the superior colliculus caused a transient reduction in the buildup and peak velocity of OKN and OKAN. 3. In terms of a previous model (Cohen et al. 1977; Waespe et al. 1983), the findings suggest that the indirect pathway that activates the velocity storage integrator in the vestibular system to produce the slow rise in ipsilateral OKN and OKAN, lies in NOT and DTN. Activity for the rapid rise in OKN, carried in the direct pathway, is probably transmitted to the pontine nuclei and flocculus via an anatomically separate fiber pathway that lies in the MRF. A fiber tract in the pulvinar that inputs to the brachium of the superior colliculus appears to carry activity related to retinal slip from the visual cortex to NOT and DTN. PMID- 2323372 TI - Corticospinal projections from areas 4 and 6 in the raccoon. AB - The corticospinal projections from areas 4 and 6 were investigated in the raccoon using the horseradish peroxidase (HRP) retrograde tracing technique. Multiple injections of lectin bound HRP and HRP were made into either the cervical or lumbar cord in 7 anesthetized raccoons. Retrogradely labeled neurons were observed throughout a wide extent of areas 4 and 6a beta. The HRP positive cells were most numerous within the dorsal bank of the cruciate sulcus within area 4 and continued around the fundus to occupy the lateral two-thirds of the ventral bank of the cruciate sulcus within area 6a beta. No labeled cells were observed in the more medially located area 6a alpha. Although the HRP positive cells observed following the lumbar cord injections were situated slightly more medial and caudal to those observed following the cervical cord injections, considerable overlap between the two projections was noted. The corticospinal projections arising from areas 4 and 6a beta in the raccoon largely correspond in location to the regions functionally defined as the primary motor cortex and the supplementary motor area, respectively. PMID- 2323373 TI - The relative efficacy of monopolar vs. bipolar electrodes in stimulation-produced analgesia. AB - Focal brain stimulation (FBS) of the periaqueductal gray (PAG) produces reliable antinociception. The use of different electrode configurations alters the distribution of excitation as well as the locus of cells being stimulated, making it difficult to compare results across laboratories. This study compared the analgesic properties of bipolar electrodes delivering biphasic current and monopolar electrodes delivering either a biphasic or a monophasic current to the ventral PAG. Naloxone reversibility of the analgesia was also tested. Results indicate that biphasic current with either monopolar or bipolar electrodes is more likely to elicit analgesia than monophasic current using monopolar electrodes. Naloxone reversed the analgesia produced by the monopolar/monophasic model, but only attenuated the monopolar/biphasic FBS and did not affect the analgesia produced by the bipolar/biphasic configuration. Biphasic current delivered through bipolar electrodes results in the sequential activation of different cell populations. Use of bipolar electrodes may widen the distribution of excitation beyond that of either monopolar configuration. Thus, a wider neural field of excitation may cause a bleedover of the field of stimulation into two systems (one opiate and one nonopiate). PMID- 2323374 TI - Functional organization of the cortical 17/18 border region in the cat. AB - The representation of the visual field in the 17/18 border region of the cat's visual cortex, and the layout of orientation and ocular dominance columns, were studied by making many closely spaced electrode penetrations into the superficial layers of the flattened dorsal region of the marginal gyrus and recording response properties at each location. The 17/18 border region was defined by measuring the change in the horizontal component of receptive field position within the gyrus: as the position of the recording electrode moved from medial to lateral, the receptive fields moved towards the vertical midline, indicating that the electrode was in area 17; as penetrations were made in increasingly lateral positions, the trend reversed, and receptive field positions moved away from the midline, indicating that the electrode was in area 18. The receptive fields of cells close to the border straddled, or lay within 2 degrees-3 degrees on either side of the vertical midline. In addition, patches of cortex were sometimes encountered in which cells had receptive field centers located up to 7 degrees in the ipsilateral visual field. Experiments in which maps were made in the left and right hemispheres of a single animal showed that these patches had a complementary distribution in the two hemispheres. Cells within the patches behaved as though driven by Y-cell inputs: they usually had large receptive fields and responded to rapidly-moving stimuli. They were broadly tuned for orientation and strongly dominated by the contralateral eye. Fourier spectral analysis of orientation selectivity maps showed that iso-orientation bands had an average spacing of 1.14 +/- 0.1 mm and tended to be elongated in a direction orthogonal to the 17/18 border. Individual bands crossed the border without obvious interruption, although singularities (points of discontinuity in the layout of orientations) were more frequently observed in the border region than in adjacent areas. Two dominant periodicities could be measured in the maps of ocular dominance, one at around 0.8 +/- 0.2 mm and a second at 2.0 +/- 0.3 mm. No constant direction of elongation was noted. These are close to the periods present within areas 17 and 18 respectively. PMID- 2323375 TI - Changes in extracellular potassium concentration in cat spinal cord in response to innocuous and noxious stimulation of legs with healthy and inflamed knee joints. AB - In 20 cats anaesthetized with alpha-chloralose and spinalized at the thoracolumbar junction we investigated the role of stimulation induced accumulation of extracellular potassium in the spinal cord in the processing of nociceptive discharges from the knee joint. For that we electrically stimulated the posterior articular nerve of the knee. We further performed innocuous and noxious stimulation of the knee and of other parts of the leg and studied the effect of an acute inflammation of the knee on [K+]0 in the spinal cord. Innocuous stimulation of the skin (brushing or touching) and innocuous movements in the knee joint all induced rises in [K+]0 which were maximal at recording depths of 1500 to 2200 microns below the surface of the cord dorsum. Peak increases were 0.4 mM for touching the leg and 1.7 mM during rhythmic flexion/extension of the knee joint. Noxious stimulation of the skin, the paw, the tendon and noxious movements of the knee joint also produced rises in [K+]0, which were somewhat larger for the individual types of stimuli than those produced by innocuous intensities. Electrical stimulation of the posterior articular nerve induced rises in [K+]0 by up to 0.6 mM. Stimulus intensities sufficient to activate unmyelinated group IV fibers were only slightly effective in raising [K+]0 above the levels reached during stimulation of myelinated group II and III fibers. During development of an acute inflammation of the knee joint (induced by kaolin and carrageenan), increases in [K+]0 and associated field potentials became larger by about 25%. We assume that this reflects an increase in neuronal responses. In conclusion, changes in [K+]0 in the spinal cord are somewhat larger during noxious stimulation than during innocuous stimulation. The absolute level reached depended more on the site and type of stimulation than on the actual stimulus intensity itself. Hence a critical role of spinal K+ accumulation for nociception is unlikely. PMID- 2323377 TI - Comparison of saccades evoked by visual stimulation and collicular electrical stimulation in the alert monkey. AB - In the alert monkey we have compared the properties of saccades elicited by a visual stimulus (V-saccades) with those generated by electrical stimulation in the superior colliculus (E-saccades). We found that whereas there exists a graded relation between E-saccade amplitude and current strength, E-saccade direction is remarkably independent of electrical stimulation parameters. At sufficiently high current strengths (about 20 microA), E-saccades are consistently directed toward the center of the movement field of nearby cells, except when stimulation is performed at sites near the collicular borders. Further interesting differences between the amplitude and direction behaviour were observed when the variability in E-saccade vectors, obtained with fixed stimulation parameters, was analyzed. In all cases, E-saccade amplitude scatter exceeds direction scatter, suggesting the possibility of a polar coordinate organization for the coding of saccade metrics. These data are compared with V-saccade scatter data, recently obtained in the human (Van Opstal and Van Gisbergen 1989c). Finally, an analysis of saccade dynamics shows that E-saccades can reach V-saccadic velocities at higher current strengths. However, at near-threshold current strengths, where E-saccade amplitude decreases, we found at most stimulation sites (22/37) that E-saccades are consistently slower than V-saccades of the same amplitude. Possible mechanisms underlying the collicular role in saccade generation are discussed. PMID- 2323376 TI - Effects of 5-hydroxytryptamine on the firing rates of neurons of the lateral vestibular nucleus in the rat. AB - 5-hydroxytryptamine (5-HT) was delivered microiontophoretically (20-80 nA) to cells of the lateral vestibular nucleus of anaesthetized rats to test its influence on the spontaneous activity of single neurons. 5-HT increased the rate of firing of 94% of the units tested. The enhancement persisted for up to 700 s after the end of the 5-HT ejection and the maximum magnitude of the excitation (10-3400%) showed a hyperbolic correlation (rho = 0.86) with background firing. In 43% of units the enhancement was preceded by a short-lasting (less than 105 s) depression of the neuronal firing rate, the magnitude of which was unrelated to the background mean firing rate. Both components of the 5-HT response were dose dependent. Only the excitatory responses were antagonized by metergoline, methysergide and ketanserin. The putative 5-HT agonist, 5-methoxy-N,N dimethyltryptamine, applied microiontophoretically, depressed the background firing rate and was not antagonized by methysergide. These results demonstrate that 5-HT modifies the responsiveness of vestibular neurons and suggest that at least two mechanisms and maybe two types of receptors are activated by 5-HT in this nucleus. PMID- 2323378 TI - Frequency dependent corticofugal excitation of principal cells in the cat's dorsal lateral geniculate nucleus. AB - Excitatory postsynaptic potentials (EPSPs) were evoked in principal cells of the cat's dorsal lateral geniculate nucleus by electrical stimulation of cortico geniculate fibres. The EPSPs had a pronounced frequency sensitivity. They were barely detectable at stimulation frequencies below 3 Hz but increased dramatically in size at higher frequencies. At 30-50 Hz their amplitude typically exceeded that of EPSPs from optic tract fibres. A prominent EPSP potentiation was also obtained with pair pulse stimulation. The findings are discussed in relation to the hypothesis that the cortico-geniculate system serves as a variable gain regulator for the visual input to the cortex. PMID- 2323379 TI - Influence of plantar cutaneous afferents on early compensatory reactions to forward fall. AB - The influence of cutaneous afferents in the compensatory reactions to a forward fall was investigated. Modification of cutaneous afferent activity was obtained in two different ways: first, by varying the initial pedal support conditions, secondly by anesthetizing the plantar foot sole. The initial pedal support conditions were: 1) bipedal posture, 2) unipedal posture, with contact and 3) unipedal posture, without contact. Nine healthy subjects participated in the control (without anesthesia) experimental session, of which three subjects participated in a session where the plantar sole was anesthetized. The compensatory reactions to a perturbation of balance of a subject initially with a bipedal stance, showed synchronized EMG activity in both Soleus muscles, starting on average at 59 ms, and a burst of EMG activity in the Tibialis Anterior of the starting foot after 200 ms. When the subject was in unipedal posture, the EMG responses on the side which was without support, showed several modifications: the EMG burst in Soleus was strikingly depressed, the response in Tibialis Anterior appeared earlier (mean latency 90 ms) and its magnitude was enhanced. When this foot was in contact with a rigid support, the Soleus showed a short burst of activity and the activity in Tibialis Anterior started at a mean latency of 150 ms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323380 TI - Plasticity in the ipsilateral visuotectal projection persists after lesions of one nucleus isthmi in Xenopus. AB - Visual input has a profound effect on the development of binocular maps in the tectum of the frog Xenopus laevis. Input from the ipsilateral eye, which is relayed to the tectum via the opposite nucleus isthmi, is normally in register with the retinotectal map from the contralateral eye. However, if one eye is rotated during larval stages while the other eye is left in normal orientation, then the resulting mismatched visual input induces the crossed isthmotectal axons to change their trajectories and to establish a reoriented ipsilateral visuotectal map in register with the contralateral retinotectal map. The major cue which aligns the two maps is the correlation of visually-evoked activity from the two eyes. This experiment was designed to determine whether the uncrossed isthmotectal projection is necessary to organize the map transmitted by the crossed isthmotectal axons. Each NI receives a topographic map from the tectum on the same side of the brain and therefore carries the same topographic information as the retinotectal projection, and each NI transmits that map not only to the opposite tectum but also back to the same tectum from which it received its input. Thus, the uncrossed isthmotectal axons provide each tectum with a map which is essentially topographically identical to the retinotecal map but which is slightly delayed temporally. The uncrossed isthmotectal axons therefore could provide topographic cues to the guide the alignment of the crossed isthmotectal axons as they establish the ipsilateral visuotectal map. In order to determine whether the uncrossed isthmotectal projection is an important source of topographic cues for the crossed isthmotectal axons, the right nucleus isthmi was ablated and one eye was rotated by 90 degrees-150 degrees in midlarval tadpoles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323381 TI - The differences in human spinal motoneuron excitability during the foreperiod of a motor task. AB - Changes in excitability of the spinal motoneuron pool during the foreperiod, which was fixed at 0.8 s, in simple and choice reaction time experiments using ankle dorsiflexion and plantar flexion were studied in fourteen healthy normal subjects by combining the visually guided tracking and H-reflex testing methods. Almost all cases showed a significant facilitation in the soleus H-reflex within the time interval between 100 and 300 ms after a warning signal (Phase I), irrespective of movement direction and task modality. The pretibial H-reflex was also facilitated. On the other hand, variable effects were noted in the later half of the foreperiod, particularly within the 200 ms prior to the response signal (Phase II). Using a simple reaction task with dorsiflexion, six cases showed no changes in the soleus H-reflex, while four others showed statistically significant inhibitory changes and the remaining four showed facilitation. The inhibition and facilitation were often accompanied with very weak and unintended EMG activities in the pretibial and So1 muscles respectively. A similar finding was obtained in the simple plantar flexion task and the choice reaction task with dorsiflexion or plantar flexion. We suggest that the facilitation at Phase I represents a perceptual orienting response to a warning signal and the effects seen in Phase II represent the difference in the waiting attitude of each subject anticipating initiation of the coming task, or the preparatory "set" which primed the spinal motor structure in a biased position. PMID- 2323382 TI - Errors in force estimation can be explained by tendon organ desensitization. AB - Here we report observations on the sense of muscle tension in human subjects and compare them with responses of tendon organs in cat hindlimb muscles. Human subjects learned under visual guidance to estimate a 4% maximum voluntary contraction (m.v.c.) of elbow flexors of one arm. When they were able to reproduce this force reliably without visual feedback, they repeated the estimation immediately after a 5 second m.v.c. or a 5 second period of relaxation. In a second experiment the 4% m.v.c. was generated under visual control with one arm, and matched with the other, test arm, without visual feedback. The matching task was then repeated after test arm conditioning. In both experiments subjects reported an accurate match using significantly more than the reference force ("overmatched") after an m.v.c. The overmatching was greatest during the first 5 second period following the conditioning contraction, and during the subsequent 20 seconds it gradually declined to near reference levels. The size of the matching error was directly proportional to the duration of the conditioning contraction. In the first experiment extension of the arm immediately following conditioning increased the error, in the second it slightly decreased it, although tension continued to be overmatched. In a series of experiments on the soleus muscle of anaesthetised cats responses of tendon organs to 10% of maximum contraction were seen to drop sharply when preceded by a conditioning maximum contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323383 TI - Movement and muscle activity during contact placing of the forelimb and their relations to other postural reactions in the cat. AB - Forelimb trajectory and the activity of eight muscles operating at the elbow, wrist and digit joints were compared during the contact placing reaction, during the swing phase of locomotion and during reactions induced by swing perturbations, to verify the hypothesis that common neural mechanisms are involved in these reactions. Both the patterns of muscle activation and forelimb kinetics during the placing reaction greatly differed from those during the swing phase of locomotion. Both similarities and differences have been found between the placing reaction and the reaction to swing perturbations. Similar latencies, patterns of muscle activation and trajectories have been found for elbow movements while considerable differences were seen in the movements of distal joints. Both reactions started with a backward and upward movement at the proximal joints which was accompanied by a locking at the elbow. At the distal joints, tactile stimuli evoked first a wrist ventroflexion during the placing reaction, whereas they induced wrist dorsiflexion to swing perturbations. A further difference between these two reactions appeared at the beginning of the extension which was highly passive during the reaction to swing perturbation and active during contact placing. These results suggest that some common, most likely spinal, reflexes are involved at the beginning of the two reactions while their extension phases are controlled in a different way. PMID- 2323384 TI - The effect of vasoactive intestinal polypeptide (VIP) on forskolin stimulated adenylate cyclase in the caudate-putamen of the rat. AB - Vasoactive intestinal polypeptide (VIP) was incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen (CP) tissue of the rat in order to examine the effect of the peptide on forskolin-activated adenylate cyclase in vitro. Forskolin induced an enhancement of cyclic AMP formation that was mediated by an effect on catalytic subunit and stimulatory guanine nucleotide regulatory protein (Ns). In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by dopamine and sodium fluoride but, in the absence of guanylylimidodiphosphate (guanosine 5'-(beta, y-imido) triphosphate) VIP inhibited the forskolin-stimulation of the enzyme in a noncompetitive manner. Met-encephalin, acting on a D-2 receptor-coupled putative inhibitory guanine nucleotide regulatory protein (Ni), inhibited the adenylate cyclase activity stimulated by forskolin to a slightly greater extent than VIP. When assayed together, these inhibition effects were additive, implying that the peptide receptors are not identical. The Ni-antagonist, MnCl2 completely blocked the inhibition of met-encephalin but had no significant effect on VIP-induced inhibition. In addition, pertussis toxin did not influence the effect of VIP on forskolin-stimulation in contrast to cholera toxin which did antagonize the VIP effect via the stimulatory guanine nucleotide regulatory protein (Ns). Furthermore, specific D-1 and D-2 dopaminergic receptor antagonists alpha(+) flupentixol and spiperone had no effect on VIP-modulated forskolin-stimulated adenylate cyclase activity. These results suggest that the neuromodulatory effect of VIP is mediated by a Ns distinct from those involved in several adenylate cyclase pools sensitive to stimulation by dopamine and VIP in the rat striatum. PMID- 2323385 TI - Stimulus characteristics influence the gain of smooth pursuit eye movements in normal subjects. AB - Impaired smooth pursuit eye movements are commonly believed to indicate a lesion of the central nervous system. Smooth pursuit performance, however, is strongly dependent on non-specific variables like cooperation, arousal and attentiveness. Therefore, disturbed smooth pursuit can be attributed either to lesions of the smooth pursuit system per se, or to the influence of non-controlled variables (non-structural disturbances). This renders the evaluation of smooth pursuit uncertain. In the present study we attempted to design a stimulus that yields smooth pursuit eye movements, which are not influenced by uncontrolled variations of state and input, for a better separation of structural lesions of the pursuit system and the effect of nonspecific variables. Our results suggest that a stimulus that leads to a centrally generated representation (percept) of motion is most suitable to elicit high gains of smooth pursuit (sigma pursuit), but only if attentiveness is optimal. Beta-motion (motion elicited by discrete steps of the target) or real target motion are capable to render the smooth pursuit performance optimal, even with low attentiveness, when the fixation point and its wider surroundings or enough discrete points in the neighbourhood move in the same direction in space. PMID- 2323386 TI - Brainstem mediation of prefrontal stimulus-produced hypotension. AB - Electrical stimulation of the prefrontal cortex (PFC) in rats produces transient hypotension. It has been suggested that this stimulus-produced hypotension (SPH) may be mediated by direct PFC projections to either the posterolateral hypothalamus or the nucleus tractus solitarius (NTS). To initially test these hypotheses, microinjections (0.5 microliters) of 4% lidocaine were made into various brainstem sites, including the posterolateral hypothalamus, the PFC-NTS pathway and the NTS itself. Most injections made into the posterolateral hypothalamus, rostral portion of the PFC-NTS pathway or NTS were successful in blocking prefrontal SPH. In comparison, the majority of injections made into numerous other brainstem sites including the caudal portion of the PFC-NTS pathway did not block prefrontal SPH. These findings support the concept that prefrontal SPH may be mediated via both the posterolateral hypothalamus and NTS. However, these findings do not support the hypothesis that prefrontal SPH is mediated by direct projections from the PFC to the NTS. To eliminate the possibility that the effects of the lidocaine injections made into the hypothalamus were due to the incapacitation of fibers alone, a series of experiments was conducted in which microinjections (0.5 microliters) of ibotenic acid, a neurotoxin that destroys perikarya but spares axons, were made into the posterolateral hypothalamus. Each of these injections resulted in the blockade of prefrontal SPH. These findings further support the role of hypothalamic involvement in prefrontal SPH. PMID- 2323387 TI - Spatio-temporal organization of the somaesthetic projections in the red nucleus transmitted through the spino-rubral pathway in the cat. AB - Although it has been known for a long time that in awake cats, natural stimulation of the skin induces short latency responses in rubrospinal cells, the pathway possibly involved has been identified only recently (Padel et al. 1988). This tract, which was described in acute, chloralose anaesthetized cats, ascends in the ventromedial spinal cord and is activated via collaterals of primary afferent fibres running in the dorsal columns of the spinal cord. The present study demonstrates that this newly described spino-rubral tract is able to send detailed somaesthetic information to the red nucleus. After lesions leaving intact only the spino-rubral pathway, excitatory and inhibitory responses to natural peripheral stimulations were recorded in identified rubral efferent cells. The most effective stimuli were touching the skin, passive joint rotation and hair displacement. Each cell was found to possess a particular receptive field. These fields which could be ipsi-, contra-, or bi-lateral were generally located on a single limb, although they could include two or more limbs, or even exceptionally the whole body with or without preferential zones. The topographic organization of receptive fields was arranged somatotopically in the red nucleus and overlapped the motor representation. The somaesthetic inputs transmitted through the spino-rubral pathway to the red nucleus are very similar to those previously observed in the intact cat, which supports the idea that this pathway may play a functional role in motor control. The spino-rubro-spinal loop may provide a fast adaptation of the descending motor command, thus producing a fine and harmonious tuning between the changing surroundings and the animal's movements. PMID- 2323388 TI - The coupling of arm and finger movements during prehension. AB - The experiments reported here were aimed at testing the degree of coupling of motor components during the act of prehension. Hand movements were recorded bidimensionnally by a Selspot system which monitored the displacement of IREDS placed at the thumb and index finger tips, at the metacarpophalangeal joint of the index and at the radial styloid. Targets were three-dimensional translucent dowels placed concentrically at 30 cm from the subject. The dowels were 10 degrees apart from each other. In blocked and control trials, one dowel was illuminated and served as a target for the movement. In the perturbed trials (20% of cases) one dowel was illuminated first and the light was unexpectedly shifted to another dowel at the onset of the subject's movements. Kinematic analysis of the movement revealed the following: 1. In blocked and control trials, the wrist moved with a single acceleration to the target dowel. Meanwhile, the finger grip (computed as the distance between thumb and index IREDS) increased up to a maximum size, located in time at about 60% of movement time and then decreased until contact with the dowel. 2. In perturbed trials the initial wrist acceleration was aborted. A new acceleration started about 180 ms after the first, in order to reorient the hand to the new target. Similarly, the initial grip aperture also aborted and reincreased in synchrony with the second wrist acceleration. 3. Perturbations increased movement time by only 95 ms on average. The first peak in acceleration indicating abortion of the initial movement occurred 100 ms after the movement onset, i.e., 30 ms earlier than in non perturbed trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323389 TI - Neurons of the nucleus tractus solitarius, in vitro, generate bursting activities by solitary tract stimulation. AB - Extracellular recordings of the activity of nucleus tractus solitarius (NTS) neurons were performed on rat brainstem slice preparations. Neurons localized in the medial part of the lateral NTS, which displayed a synaptic response to single pulse stimulation of the tractus solitarius (TS), generated bursting activity following repetitive TS stimulation (20-50 Hz frequency, 100-600 ms duration). According to their patterns of discharge and to the duration and frequency of their bursting activities, these neurons were classified in three groups called type A, B and C. We suggest that different cellular intrinsic properties, rather than local synaptic interactions, might be involved in the generation of these three types of bursting activities. These results are discussed in terms of the role of NTS neurons in the generation of the swallowing motor pattern. PMID- 2323390 TI - Corticofugal feedback influences the responses of geniculate neurons to moving stimuli. AB - Geniculate cell responses to moving bars and moving texture were compared in normal cats and in cats in which the corticofugal feedback was removed by cortical ablation. In experimental animals the response strength and the velocity upper cutoff assessed with a moving bar was reduced compared to control animals. The strength of response to texture decreased even more after cortical ablation, which also changed the response pattern of X cells to moving texture. These data suggest that corticofugal feedback contributes to the geniculate responses to moving stimuli and in particular to moving texture. PMID- 2323391 TI - On the evolutionary history of the circumsporozoite protein in plasmodia. AB - We report the complete nucleotide sequence of the circumsporozoite (CS) gene of Plasmodium brasilianum and present an analysis of its evolutionary profile. Despite the lack of a reliable time scale, the analysis of the number and distribution of fixations among seven taxa provides a first glimpse of the evolutionary history of the CS gene, and suggests that the branching events of this gene are completely unconnected with--and far precede in time--the speciation event of the parasite's vertebrate hosts. PMID- 2323392 TI - Schistosoma mansoni: levels of antioxidants and resistance to oxidants increase during development. AB - The effects of cell-free generated oxidants on migrating and developing stages of Schistosoma mansoni were investigated and the levels of antioxidant enzymes and of glutathione were determined for each stage. Schistosomula and 2-week-old parasites recovered from the livers of infected mice showed similar susceptibility to killing by added hydrogen peroxide and t-butylhydroperoxide. However, when glucose (0.5 mM)-glucose oxidase (2.5 mU ml-1) and xanthine (0.5 mM) or hypoxanthine (0.5 mM)-xanthine oxidase (5.0 mU ml-1) systems were used to generate hydrogen peroxide and oxygen free-radicals, schistosomula were more susceptible to oxidative killing than the 2-week-old parasites. The 4- and 8-week old worms were more resistant to oxidants than all of the younger stages. High levels of superoxide dismutase (16.2-24.8 U mg-1 protein) were present in all stages. Catalase was not detected. Glutathione peroxidase activity with cumene hydroperoxide as substrate was not detectable in the schistosomula but the activity was present in the 2-week-old parasites. However, hydrogen peroxide sensitive glutathione peroxidase activity was present in all the stages with a threefold difference in activity between schistosomula and the adult stages. Glutathione-s-transferase activity was significantly lower in the schistosomula, lung stages, and the 2-week-old parasites than in the older stages. Progressive increases in the levels of glutathione reductase and glutathione were also observed with development. The differences in the levels of antioxidants between different stages of development may partly explain the increase in resistance to oxidant-mediated damage as the parasite develops. PMID- 2323393 TI - Hymenolepis diminuta: the effect of cold temperature exposure on infections in mice. AB - Hymenolepis diminuta grown in mice maintained at 5 degrees C were significantly larger and markedly more developed than those grown simultaneously in control mice maintained at 21 degrees C. In mice maintained at 5 degrees C, the incidence of infection and the number of worms recovered per host were higher than in the mice kept at 21 degrees C. Regardless of the temperature of the hosts' external environment, primary infections were always expelled before Day 13 postinfection and secondary (challenge) infections were invariably lost before Day 7. PMID- 2323394 TI - Babesia bovis: evidence for selection of subpopulations during attenuation. AB - DNA probes were used to detect variation in subpopulations of virulent and serially passaged Babesia bovis. Two distinct patterns were evident after hybridization to genomic DNA; the first was a basic profile typical of virulent B. bovis and the second, a more variable array, was characteristic of B. bovis after various stages of attenuation. Tick transmission of avirulent B. bovis causes reversion to the virulent genomic pattern, suggesting that selective enrichment of a small residual subpopulation caused reversion to a virulent profile of subpopulations. Certain genomic fragments, predominant in either virulent or avirulent parasite forms, are putative "markers" or actual elements responsible for these biological characteristics. PMID- 2323395 TI - Plasmodium chabaudi: in vivo effects of Ca2+ antagonists on chloroquine-resistant and chloroquine-sensitive parasites. AB - The effects of Ca2+ antagonists, verapamil, nicardipine, and diltiazem, on susceptibility to chloroquine were examined in mice infected with chloroquine sensitive and chloroquine-resistant lines of Plasmodium chabaudi. In mice that received no chloroquine, daily injections of 50 mg/kg of verapamil, nicardipine, or diltiazem did not affect the growth of both sensitive and resistant parasites. When mice were injected daily with verapamil plus 2 to 3 mg/kg chloroquine, the chloroquine-sensitive parasite became more susceptible to chloroquine than the parasite in mice given chloroquine alone. On the other hand, in mice infected with chloroquine-resistant parasites, verapamil severely suppressed the growth of the parasite when accompanied by daily injections of 2 to 3 mg/kg of chloroquine, at which doses resistant parasites grew steadily in the absence of verapamil, indicating reversal of chloroquine resistance. This reversal was dose-dependent between 5 and 50 mg/kg of verapamil. Daily injections of nicardipine or diltiazem at 50 mg/kg also reversed resistance to chloroquine in resistant parasites. These results indicate that Ca2+ antagonists increase the susceptibility to chloroquine in a sensitive line of P. chabaudi and reverse chloroquine resistance in a resistant line. PMID- 2323396 TI - Trichinella spiralis: major histocompatibility complex-associated elimination of encysted muscle larvae in swine. AB - A heretofore undescribed host-mediated reactivity against encapsulated muscle larvae (ML) of the nematode Trichinella spiralis is reported. Inbred miniature swine (NIH minipigs) of three independent SLA phenotypes, which received a primary oral dose of 300 T. spiralis ML, successfully resisted a secondary infection of 10,000 ML; however, only pigs of the SLAa/a phenotype exhibited an unusual and highly significant reduction in the numbers of encysted ML from the primary infection (P less than 0.0003). This initial anti-encysted ML reactivity was confirmed in subsequent trials by comparing the prechallenge ML burdens with the reduced ML numbers in primary-infected aa pigs after challenge. Analyses of inbred strains of mice, selected for major histocompatibility type and for resistance or susceptibility to infection with T. spiralis, showed no such anti encysted ML response. Because elimination of encysted T. spiralis ML had been accomplished previously only through selected drug regimens, our demonstration of a nonpharmacological, host-mediated reactivity against this stage of the parasite in swine highlights the importance of MHC genes in regulating disease resistance in a livestock species. PMID- 2323397 TI - Trichinella spiralis: altered expression of muscle proteins in trichinosis. AB - Mammalian muscle undergoes significant alterations morphologically, ultrastructurally, and biochemically following infection by Trichinella spiralis larvae. To investigate this host/parasite relationship in more detail, a new method to isolate T. spiralis-infected cells (nurse cells) in preparative quantities was developed. Nurse cells isolated by sequential protease treatments contain larvae and retain many of the characteristics of those in situ. When analyzed by SDS-PAGE, a wide range of proteins detected in nurse cells were not apparent in muscle by the methods employed. Proteins associated with the nurse cell capsule and organellar fractions appear to account for most of the dominant nurse cell proteins. In contrast, most major muscle proteins were either reduced in abundance or undetectable in nurse cells. The myofibrillar proteins myosin heavy chain, alpha-actin, and alpha- and beta-tropomyosin were identified using antibody reagents and two-dimensional PAGE analysis. None of these proteins were detectable in nurse cells and except for beta-tropomyosin, the relative abundance of these proteins was a minimum 100-fold lower compared to muscle. The data indicate that the reduction of muscle products in the nurse cell is much greater than previously reported. The inability to detect myofibrillar proteins raises the possibility that the nurse cell is not blocked in a regenerating muscle phenotype as previously suggested. Availability of isolated nurse cells in large quantity should facilitate resolution of this and other issues regarding the T. spiralis/skeletal muscle relationship. PMID- 2323398 TI - Angiostrongylus cantonensis: in vitro cultivation from the first-stage to infective third-stage larvae. AB - The first-stage larvae of Angiostrongylus cantonensis were cultured in various media at 27 degrees C. The most suitable medium for the development was Chernin's balanced salt solution supplemented with 10% L-15, 10% tryptose phosphate broth, 20% fetal calf serum, and 26 mM sodium bicarbonate. Addition of sodium bicarbonate to the medium facilitated early development of the first-stage larvae. When the first-stage larvae were cultured in the medium under 5% CO2 in air, the worms developed gradually to become quiescent and showed the C shape. Thereafter, the larvae developed to the second stage, retaining their first sheath. About 23 days later, the larvae began to develop to the third stage, being enclosed within the sheaths of the first and second molts. Under these conditions, the larvae developed uniformly and 82% of the larvae reached the third stage 50 days later. About 70% of the third-stage larvae discarded their two sheaths, showing almost the same size as those obtained in vivo. When these exsheathed larvae were inoculated into rats, they developed into adult worms and deposited numerous first-stage larvae. PMID- 2323399 TI - Trypanosoma congolense: complement independent immobilization by a monoclonal antibody. PMID- 2323400 TI - Solubilization and partial purification of glycerol-3-phosphate oxidase from mitochondria of Trypanosoma brucei. PMID- 2323401 TI - Loa loa: identification of genomic DNA clones expressing recombinant antigens. PMID- 2323402 TI - Helping teenagers postpone sexual involvement. AB - In 1983, the Henry W. Grady Memorial Hospital in Atlanta began a family planning based outreach program for eighth graders in a local school system. The program is led by older teenagers and focuses on helping students resist peer and social pressures to initiate sexual activity. Evaluation of the program, based on telephone interviews with 536 students from the hospital's low-income population, revealed that among students who had not had sexual intercourse, those who participated in the program were significantly more likely to continue to postpone sexual activity through the end of the ninth grade than were similar students who did not participate in the program. Because of their lower rate of sexual activity, program students also experienced comparatively fewer pregnancies than no-program students. PMID- 2323403 TI - Teenage pregnancy in Canada, 1975-1987. PMID- 2323404 TI - Prenatal care in the United States: reports call for improvements in quality and accessibility. PMID- 2323405 TI - More on Koop's study of abortion. PMID- 2323406 TI - A focal point of HIV infection. PMID- 2323407 TI - Maternal HIV transmission: a clue? PMID- 2323408 TI - Recurrence and survival after abdominoperineal and low anterior resection for rectal cancer, without adjunctive therapy. AB - Sphincter-saving operations for rectal cancer are performed with increasing frequency. In the present study outcome after low anterior resection (LAR) was compared with outcome after abdominoperineal resection (APR). Morbidity, mortality, local and distant failure and survival were retrospectively studied in 68 patients, surgically treated for rectal cancer without adjunctive therapy between 1980 and 1985. APR was performed in 29 patients (27 for cure) and LAR in 39 (32 for cure). Mean follow-up time was 60 months (range 39-95 months). Groups were comparable with regard to age and Dukes' staging, but not for location of the tumour. Anastomotic leakage was present in 15% after LAR; morbidity was otherwise similar in both groups. Hospital mortality was 5% after LAR and 0% after APR. Local recurrence occurred after a mean period of 17 months: in 15% after curative APR and in 13% after curative LAR. Distant recurrence was detected after a mean period of 28 months: in 30% after curative APR and in 26% after curative LAR. Estimated cumulative 5-year survival was not statistically different, with 72% after LAR and 59% after APR. These findings confirm that LAR does not lead to higher recurrence than APR in the treatment for rectal cancer. PMID- 2323410 TI - Feasibility of transposition of the ovaries in the surgical and radiotherapeutical treatment of cervical cancer. AB - Ovaries are seldom subject to metastases and therefore their preservation is possible in radical cervical cancer surgery. However, with postoperative radiotherapy they cannot be preserved unless they are placed outside the radiation field. The practicality of this transposition was analysed in a series of 126 patients with cervical cancer. The ovaries were transposed intraperitoneally in a lateral and cranial direction in 44 of the 64 women under the age of 50 years. In 16 of these 44 women, only one ovary could be preserved and transposed. A critical analysis was performed of the ovaries' new location by plotting their position, marked by 2 clips each, in a single pelvis. In 68% of the women at least one ovary was placed outside the radiation field. However, because of scattered radiation, i.e. 5% of the total radiation dose at a distance of 4 cm outside the radiation field, a substantial loss of ovarian function may occur. In 32% of the women at least one ovary received less than this 5%. Optimal transposition may be achieved after extension of the abdominal incision. However, this will be unnecessary in most cases, since postoperative radiotherapy will be indicated in only approximately 15% of the women. PMID- 2323409 TI - Extent of metastatic axillary involvement in 1446 cases of breast cancer. AB - One thousand, four hundred and forty-six patients with carcinoma of the breast treated with Halsted mastectomy (167), Patey mastectomy (732), and conservative surgery with axillary dissection, either at the same time (340), or separately (207), were evaluated with regard to the number and distribution of axillary lymph nodes. A total of 29,378 were removed and examined, on average 20.3 per patient. The average number of nodes was 13.5 at the first level, 4.5 at the second and 2.3 at the third. The same number of nodes were removed in patients treated with extensive surgery, such as Halsted mastectomy and limited surgery such as lumpectomy and in independent axillary dissection. In 839 cases metastases were found in the axilla. The average number of involved nodes was 6.4. Out of 839 patients, the first level was the site of metastases in 828, the second level in 364 and the third in 187. When a single lymph node was involved, it was nearly always at the first level. In only 11 cases, were the second and/or third levels invaded without metastases at the first level. Therefore, the percentage of cases with skipping metastases was very low (1.3%). It appears from the present data that the spread of breast cancer to the axilla follows a regular pattern; the first level is invaded first, whilst in most cases, the second and third levels are involved only when the first is substantially affected. PMID- 2323411 TI - Tumour metastasis from multiple myeloma in Hickman catheter tract. PMID- 2323412 TI - Neglected cases of papillary and follicular thyroid carcinoma. Occurrence of subcutaneous scalp metastases. AB - Three cases, two follicular and one of papillary thyroid carcinoma are reported. All three patients presented with subcutaneous cystic scalp metastases; they had a long-standing history of thyroid cancer, although two had never sought medical attention. We discuss this unusual clinical manifestation in patients with untreated well differentiated thyroid carcinoma. PMID- 2323413 TI - Hepatic arterial infusion (HAI) chemotherapy for liver metastases of colorectal cancer using 5-FU. AB - Thirty-three patients with liver metastases of colorectal cancer were treated by intra-arterial 5-FU chemotherapy. The median survival time of all patients was 14 months. A partial remission could be observed in nine patients, and a further 15 patients had stable disease. Patients were treated on an outpatient basis and the toxicity of treatment was mild. We observed no case of sclerosing cholangitis or chemical hepatitis. Intra-arterial 5-FU chemotherapy provided treatment results similar to those reported for FUdR but with less hepatobiliary toxicity. PMID- 2323414 TI - Articles presented at the third meeting of the European Society for Vascular Surgery. Malmo, September 1989. PMID- 2323415 TI - Vascular surgery--what is the future? PMID- 2323417 TI - Small aortic aneurysms. PMID- 2323416 TI - Chlorhexidine baths. PMID- 2323418 TI - Does prostaglandin E1 and superoxide dismutase prevent ischaemic spinal cord injury after thoracic aortic cross-clamping? AB - The beneficial use of prostaglandin E1 (PGE1) and superoxide dismutase (SOD) on the tolerance to ischaemia of the spinal cord was evaluated following thoracic aortic cross-clamping in dogs. Aside from spinally evoked somatosensory potential (SEP) by means of a bipolar epidural catheter, postoperative evaluation of motor deficits was used to determine the efficiency of pharmacological protection when compared with controls. The animals were divided into four groups. Group I (n = 12) served as controls. The dogs of Group II (n = 12) were treated with PGE1 (100 ng/kg/min) during clamping and the first hour after declamping. In the third group (n = 12) SOD was given as an intra-arterial bolus (1 mg/kg) prior to declamping which was followed by a continuous perfusion (0.4 mg/kg/min) into the carotid artery for 25 min. In Group IV (n = 12) the dogs were treated with a combination of PGE1 and SOD in the same manner as in Groups 3 and 4. Results after pharmacological protection were significantly better than controls. In Group I all animals but one (92%) were paraplegic, as were five in Group II (42%) and eight in Group III (67%). In contrast no dog in Group IV developed paraplegia. There was a close correlation of SEP and postoperative recovery. The group with combination therapy (PGE1 plus SOD) was characterised by a loss of the evoked potential for a mean of 15 min, the PGE1 group for 45.8 min and the SOD group for 58.5 min. While the control group was characterised by a loss of 72.7 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323419 TI - Effects of shear stress on endothelial cell monolayers on expanded polytetrafluoroethylene (ePTFE) grafts using preclot and fibronectin matrices. AB - Animal studies have shown that endothelial seeding of vascular prosthetic grafts reduces thrombogenicity and improves their patency. However, for endothelial seeding to be of clinical benefit in humans, it must withstand shear stress of blood flow. Endothelial cells labelled with Indium-111-oxine were seeded in supra confluent densities on preclot or fibronectin coated ePTFE graft segments over a period of 90 min. These grafts with rapidly formed endothelial cell monolayers were then exposed to varying shear stresses up to a flow rate of 300 ml/min, using tissue culture medium in an artificial flow circuit. Grafts coated with preclot matrix showed 2 h cell retentions of 82.4 +/- 6.8% at 25 ml/min, 79.9 +/- 8.2% at 100 ml/min, 75.4 +/- 9.5% at 200 ml/min and 58.3 +/- 15.5% at 300 ml/min whilst those for the fibronectin matrix were 57.8 +/- 9.9%, 55.2 +/- 13.3%, 55.4 +/- 12.9% and 56.5 +/- 15.2% respectively. Overall the preclot matrix was found to be better than fibronectin (P less than 0.001). Light and scanning electron microscopy revealed well-formed endothelial cell monolayers retained on preclot matrix up to a flow rate of 200 ml/min whereas uncovered patches were seen at 300 ml/min and at all flow rates on fibronectin matrix. PMID- 2323420 TI - Venous function assessed during a 5 year period after acute ilio-femoral venous thrombosis treated with anticoagulation. AB - To determine the chronological changes of venous physiology following major thromboses, 20 patients were repeatedly examined for over 5 years after an acute ilio-femoral thrombosis which was treated with conventional anticoagulation. Radionuclide angiography showed that 70% of the patients had obstructive lesions of the iliac vein with only minor changes occurring from 6 months to 5 years. In spite of this, the plethysmographic maximum venous outflow increased from 31 to 45 ml/min/100 ml (P less than 0.001). The foot volumetric reflux did not change with time and about half of the patients had abnormal values. Venous reflux assessed by the refill time of foot vein pressure, deteriorated with time (P less than 0.05), and at 5 years all but one patient had a refill time less than 20 s. The muscle pump function, examined by foot volumetry, was abnormally low in about half of the patients throughout the study. The ambulatory foot vein pressure was constantly pathological (greater than 60 mmHg) in half of the patients and only two of 18 patients had normal values (less than 45 mmHg) at 5 years. Five patients with thromboses involving only the proximal veins had better physiological results than 15 patients with thromboses that extended to the peripheral veins. Three patients who developed venous claudication had iliac vein obstruction and an impaired venous outflow and three patients who developed venous ulcers had venous reflux and severe venous hypertension. Although venous outflow continuously improves following ilio-femoral thromboses, valvular competence and muscle pump function are constantly pathological, creating severe venous hypertension with a risk of post-thrombotic sequelae. PMID- 2323421 TI - Cellular and immunologic features of carotid artery disease in man and experimental animal models. AB - A better understanding of the pathogenesis of atherosclerosis and of post surgical intimal hyperplasia can be obtained by analysis of the cellular composition of the lesions using immunohistochemical techniques. In the present study, we have compared human atherosclerotic plaques obtained as endarterectomy specimens from the carotid artery, with lesions induced by mechanical injury and cholesterol feeding in rats and rabbits. Antibodies to cell type-specific antigens were used to identify cells, and visualisation was with enzyme conjugated second antibodies. Our data show that the lipid core region of the human plaque is dominated by macrophages. Such cells also dominate the lesions of cholesterol-fed rabbits. In contrast, intimal lesions induced by balloon catheters in rats consist almost entirely of vascular smooth muscle cells, with a small inflammatory infiltrate of monocytes and T lymphocytes. This situation resembles that in the fibrous cap region of the human plaque. However, the human lesion contains a much higher proportion of T lymphocytes and macrophages than the experimental one. In all types of lesions, class II major histocompatibility antigens were induced on the cells, suggesting that an immune reaction with activation of T lymphocytes may be taking place. Finally, different subpopulations of smooth muscle cells were observed, possibly representing different degrees of differentiation or a response to immune mediators. In conclusion, our studies demonstrate that different experimental models resemble the human disease in various aspects. The choice of experimental model will therefore depend on the problem to be studied. The balloon catheter model should be ideally suited for studies of intimal hyperplasia after surgery and also for studies of fibrous cap formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323422 TI - Role of magnetic resonance imaging in the evaluation of aortic graft healing, perigraft fluid collection, and graft infection. AB - The authors report their preliminary experience in the use of Magnetic Resonance Imaging (MRI) in ten patients who underwent aortic reconstruction. Examinations were performed 1, 4, 12 and 24 weeks after surgery, to examine the presence, size, magnetic characteristics and evolution of periprosthetic collections. The results have shown that periprosthetic collection can be considered normal after aortic reconstructive surgery, because such a perigraft collection (PFC) was present in 90% of the patients studied 1 week after operation, and had disappeared within 24 weeks in all cases. The magnetic characteristics were evaluated by T1 [repetition time (TR) = 480 msec and echo time (TE) = 20 msec] and T2 weighted spin-echo sequences (TR = 1800 msec and TE = 70/120 msec). Variations in the magnetic characteristics, found in sequential examinations, correlated with modifications of the collection and suggested that it was originally blood. The MRI examination performed 24 weeks after surgery gave a low signal intensity in T1 and T2 weighted sequences (w.s.) suggesting periprosthetic fibrosis. These preliminary observations may constitute a starting point for better evaluation of the normal appearance and evolution of the periprosthetic fluid collections following aortic graft implantation and, may be useful for the early detection of infection especially in asymptomatic patients. PMID- 2323423 TI - The mid-aortic dysplastic syndrome. Surgical considerations with a 2 to 18 year follow-up and selective histopathological study. AB - Mild-aortic dysplastic syndrome is usually presented with advanced hypertension in young individuals in association with either weak or absent femoral pulses, due to diffuse narrowing of the aorta in its mid thoraco-abdominal course. There is frequent involvement of visceral arterial branches such as renal and superior mesenteric arteries. Although the disease has been popularised by the appealing name of "abdominal coarctation", the term mid-aortic dysplastic syndrome is more appropriate. In spite of the fact that the syndrome was described almost three decades ago, its exact aetiology remains obscure and pathogenesis speculative. Surgical revascularisation remains the only therapeutic remedy, in dealing with this particular group of young hypertensive patients. The clinical presentation, angiographic assessment and long-term outcome, following reconstruction in 11 patients (mean age 24.4 years) with mid-aortic dysplastic syndrome were evaluated, in an effort to determine the effectiveness of surgery. Late follow up, slightly exceeding 16 years (mean 5.6 years) has shown normal and relief from hypertension in practically all individuals. Furthermore, in order to elucidate at least some aspects of histopathology, studies were undertaken upon specimens from the aortic wall and the renal, carotid, lumbar and brachial arteries. The results suggested predominantly dysplastic features in the media, intima and particularly along the course of internal lamina. Aortography, using different projections, revealed variable patterns of high mid-aortic stenosis with or without associated renal artery disease. All patients were hypertensive (mean blood pressure 170 mmHg) and co-exist renal artery disease, unilateral in three and bilateral in three cases, was detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323425 TI - [Hygienic rules for the use of synthetic polymeric materials in coal mines]. PMID- 2323424 TI - Comparison of risk factor and left ventricular stroke work index as predictors of cardiac complications in vascular surgery. AB - The peak left ventricular stroke work index developed in response to rapid volume infusion was calculated in 34 patients undergoing either aorto-iliac or peripheral vascular surgery. The average preoperative maximum stroke work index in patients recovering without cardiac complication was 0.47 (+/- 0.2) J/m2 compared with a mean value of 0.28 (+/- 0.14) J/m2 in patients with perioperative cardiac complications. This difference was significant (P less than 0.01). Clinical cardiac risk analysis identified a group of high risk patients in which more than half developed cardiac complications and a low risk group in which no cardiac complications were observed. There was a significant difference in maximum stroke work indices in these two groups. PMID- 2323426 TI - [The management of labor in women with obesity]. PMID- 2323427 TI - [Endocrine sterility in women]. PMID- 2323428 TI - [The polycystic ovary syndrome]. PMID- 2323429 TI - [The crush syndrome (its etiology and pathogenesis)]. PMID- 2323430 TI - [The clinical evaluation of blood analyses]. PMID- 2323431 TI - [Meniscal injury to the knee joint]. PMID- 2323432 TI - [Complications after endoprosthesis of the hip joint]. PMID- 2323433 TI - [The characteristics of fractures in the elderly]. PMID- 2323434 TI - [Deontology, the culture of work and ethics in medicine]. PMID- 2323435 TI - [The traditional medicine of Vietnam: its history and use in clinical practice]. PMID- 2323436 TI - [The quality control of the operation of sterilization apparatus in medical and prophylactic institutions]. PMID- 2323437 TI - [Characteristics of physico-chemical properties of circulating erythrocytes in the post-anoxia period]. AB - The normobarometric hypoxic hypoxia stimulates different alterations in the fundamental parameters of physicochemical properties of the peripheric blood erythrocytes and has a stimulating effect on the system of the erythropoiesis in post-hypoxia period. PMID- 2323438 TI - [An apparatus for artificial circulation in laboratory animals]. AB - An artificial circulation apparatus consisting of two membrane pneumatic adaptive diaphragmatic-type pumps and artificial film-type lungs and principle of its operation are described. The apparatus permits maintaining volume blood flow to 800 ml/min during organism resuscitation after endured clinical death including prolonged one as well. PMID- 2323439 TI - [Study of catecholamine secretion by the rat adrenal glands using microdialysis in vivo]. AB - Microdialysis technique has been developed to study secretory function of the adrenal gland in anesthesized rats. Concentration of adrenaline and noradrenaline in sequential 20 min microdialysis samples was measured by HPLC with electrochemical detection. The suitability of method was tested by local and central stimulation of catecholamine secretion. In the first case 100 mmol of KCl or 1 mmol of carbachol were added to perfusion medium, in the second one hypovolemic hypotension was applied. All the stimuli used increased catecholamine levels in the adrenal gland dialysates. Institute of Experimental Cardiology of the All-Union. PMID- 2323440 TI - [Effect of the antihypoxic agent ionol on the morphofunctional state of the air blood barrier of the lungs in hypoxic anoxia]. AB - It is shown that antihypoxic ionol has promoted normalization of the air-blood lung barrier ultrastructure, activation of the surfactant system under acute hypoxic hypoxia effect as well as compensatory redistribution of the thickness of separate barrier layers due to intensified synthesis of phospholipids which are the components of cytoplasmic membranes and pulmonary surfactant. PMID- 2323441 TI - [Effect of the destruction and activation of the caudate nuclei on the convulsive action of corazol kindling]. AB - Chronic experiments on the rats have shown that the pharmacological destruction of caudate nuclei significantly elevates the general brain excitation and induces rapid development of the corazol kindling. The hippocampal destruction exerts an opposite effect. Regression analysis of this processes has shown that mechanism of the general brain excitation and those of epileptogenesis are different on the stage of the developing kindling. Caudate nucleus activation induces powerful inhibition of kindling behavioral convulsive reactions and its electrographic epileptic activity. These data suggest that the caudate nucleus is a significant structure of the antiepileptic brain system and confirm G. N. Kryzhanovsky's concept about the system-antisystem interrelationship in case of neuropathologic syndromes as a result of the system hyperactivity. PMID- 2323442 TI - [Prevention of stress-induced changes in coronary autoregulation of vasodilative reserve of the coronary vessels and contractile function of the isolated heart with small doses of thyroid hormones]. AB - The possibility to restrict stress disturbances of coronary blood flow and contractile myocardium function with small doses of thyroid hormones has been studied on 46 hearts of female rats isolated by the Langendorff method. It is found that small doses of thyroidin increase the force of systoles and adequately increase relative coronary blood flow, coronary reserve vasodilatation, significantly prevent stress disturbances of coronary autoregulation, the force and rate of the myocardium contraction and relaxation, that restricts disproportion between contractive function and coronary blood flow. PMID- 2323443 TI - [Changes in the activity of granulocytopoiesis during increasing and reducing the reactions of the lysosomal apparatus of circulating neutrophils in hypovolemic hypotension]. AB - An interrelation between the intensity of release of the lysosomal content of circulating neutrophils and the activation degree of granulocytopoiesis and neutrophilia was revealed by means of pharmacological influence on the lysosomal membrane stability in case of hypovolemic hypotension in rabbits. The activation of granulocytopoiesis and neutrophilia increased while intensifying the release of lysosomal factors from the circulating neutrophils and sharply decreased while restricting it. The intensity of hypotension decreased while intensifying the reaction of the lysosomal apparatus of circulating neutrophils and increased while depressing the reaction. PMID- 2323444 TI - [Iodine, carbohydrate and protein metabolism in rats receiving insufficient amount of iodine in the feed]. AB - Significant changes in the iodine, carbohydrate and protein metabolism are observed under conditions of prolonged iodine deficiency in the rat ration. The reason-consequent correlations between the main links of iodine metabolism are shown. Indices of protein and carbohydrate metabolism are stated to depend on the concentration of protein-bound iodine in blood. PMID- 2323445 TI - [Iodine, carbohydrate and protein metabolism in rats with iodine, copper and cobalt deficiency]. AB - Insufficient supply of white rats with I, Cu, Co for 2.5 months has induced disturbances of iodine, carbohydrate and protein metabolism which are reliably more significant than those in rats with deficiency of only iodine in the ration. The correlation-regression analysis of results from these observations shows cause-consequent relations of changes in main links of iodine metabolism as well as changes in PCI concentrations and indices of carbohydrate and protein metabolism with deficiency of I, Cu and Co in the body. PMID- 2323446 TI - [Study of the restoration and balance of thiamine in the tissues of albino mice in alcoholic intoxication]. AB - Acute inhalative alcoholic intoxication has been studied for its effect on the influx and level of free and bound thiamine in tissues of white mice. It is established that acute inhalative ethanol intoxication increases 35S-thiamine incorporation in tissues and decreases the level of endogenic free and bound thiamine. The results obtained permit a conclusion on intensification of the thiamine renewal in tissues with its sufficient influx from outside as affected by the ethanol narcosis. PMID- 2323447 TI - [Characteristics of the long-term effects of niphtholide on the functional state of the testes in animals]. AB - Long-term application of non-steroid antiandrogen niphtholid (10 or 25 mg/kg daily for 8-9 months) exerts a stimulating effect on the functional state of testicles. This effect is more pronounced in rats, than in dogs and guinea pigs. In all these animals the drug antiandrogenic effect caused a decrease of the prostatic mass, while in rats--an increase of the adenohypophysis mass. The peculiarities of the niphtholid effect in various animals should be taken into account when evaluating and interpreting investigation results. PMID- 2323448 TI - [Study of tissue coagulation factors of native and cryopreserved bone marrow]. AB - Status of thromboplastin, antiheparin and antithrombin characteristics of the native and cryopreserved bone marrow was studied experimentally on 12 rabbits. It is found that both the native and cryopreserved bone marrow possesses a pronounced and dilution resistant thromboplastin activity, whereas antithrombin and heparin activities were statistically unauthentic. In that connection the bone marrow injected into blood circulation may have different effects depending on the initial state of the recipient blood coagulation. The fact should be taken into account in clinics. PMID- 2323449 TI - [Single auditory evoked responses of the temporal and associative regions of the cerebral cortex in conscious cats]. AB - In awake cats single realizations of acoustic evoked responses (AER) from temporal, parietal and frontal cortex were registered and compared with averaged responses obtained by means of optic superposition of the same realizations. It is shown that the composition of these different realizations considerably varies due to inconstancy of manifestation of each component. The fact that the preceding component falls out does not exclude manifestation of the following one, which proves the functional independence of the mechanisms producing each component. The simultaneous registration of single realizations of AERs of different cortical areas shows that the reactions of frontal and parietal areas are independent of AERs of the temporal cortex. PMID- 2323450 TI - [Natural antistaphylococcal immunity in a potential donor population]. AB - Blood serums of 1842 donorable Kiev inhabitants have been examined. It is shown that blood serum of people with different group belonging (by the ABO system) contains natural antialphastaphylolysins during the whole year. High titres of antialphastaphylolysins (3.0.10(3) ME/1-5.0.10(3) ME/1) are most frequently revealed among the persons of donorable age with group belonging A (II) in summer and spring. PMID- 2323451 TI - [Immunocorrecting properties of low-frequency ultrasound]. AB - The possibility to correct the secondary immunodeficient state by means of two- and three-fold low frequency ultrasound effect on the spleen has been demonstrated on mice of CBA strain. It makes it possible to use low-frequency ultrasound on a large scale in the clinical practice. PMID- 2323452 TI - [Lipids in the lungs and alveolar surfactant in anaphylactic shock]. AB - The process of anaphylactoid response of rats to introduction of egg protein is associated with a decrease of the pulmonary surfactant surface activity. The factors of metabolic surfactant inactivation are as follows: protein accumulation, the disturbance of lipids transport between pulmonary cells and alveolar surface, change in fatty-acidic composition of surfactant phospholipids. The isolation of arachidonic acid from surfactant phospholipids in anaphylactoid shock is an evidence for the participation of the pulmonary surface-active phase in the process of biosynthesis of the lipid mediators in respiratory organs. PMID- 2323453 TI - [Surface-active properties of pulmonary surfactant and the functional activity of type II alveolocytes at various times of the day under experimental conditions]. AB - Complex examination of lungs in 24 healthy guinea pigs in different periods of day using physicochemical, biochemical and electron-microscopic methods has revealed that the highest surface activity of the pulmonary surfactant (PS) is observed in the evening and at night, as phospholipids contain the highest amount of a surfactant of the phosphatidylcholine fraction the most active in the surface-active respect. An increase in the content of PS phospholipids in this period of the day appears to be a consequence of synthesis and secretion intensification in the second-type alveolocytes, that may be due to an increased effect of the vagus nerve. PMID- 2323454 TI - [Effect of acute stress on glucose resorption by an isolated loop of the small intestine]. AB - In the experiments on rats acute stress is found to accelerate glucose resorption by isolated loop of small intestine in situ and it probably depends on increased level of corticosteroids. Glucose resorption changes in small intestine is of adaptable character during stress. PMID- 2323455 TI - [Cytochemical study of the natural resistance of the body in Trichophyton rubrum induced mycosis (tinea)]. AB - Clinical-cytochemical examination of 27 patients with tinea has permitted estimating nonspecific immune status of an organism. The NBT-test is shown to be highly informative and active. Differences in metabolic activity of phagocytizing subpopulations of peripheral blood are revealed. The results obtained underlie the development of the pathogenetically substantiated therapy method using diucyphon and chlorophyllipt, immunomodulators of different pharmacological groups. PMID- 2323456 TI - [Contraindications for dental implantation, proposals for conventional prosthetic rehabilitation in cases not suitable for implantation]. PMID- 2323457 TI - [Results of the caries prevention program in Gdollo. I. Cariologic studies]. AB - The caries prevention programme was begun in 1982 and the first control screening test was carried out with children of 3, 6, 9 and 12 years of age in 1986/87. Two data characteristic of efficiency: during the five years of the programme: the ratio of caries free children at the age of 6 years increased from 14.7% to 27.4% and the DMF-T value of the 12 years old was 3.52 in the group under care (national average 5.07). PMID- 2323458 TI - [Results of the caries prevention program in Godollo. II. Periodontal studies]. AB - For measuring the mouth hygiene the OHI-S index and for judging the gingivitis the PMA index were used in the screening tests of 1982 and 1986/87. As the result of the education for intensive mouth hygiene the OHI-S value diminished from 1.38 to 0.51 at the age of 3 years and from 1.17 to 0.44 at the age of 6 years. The gingivitis reduction was 30% at the age of 3 years while at the age of 6 years it was but 10%. The more grave gingivitis (PMA 2-3) disappeared. All that may exemplify that the mouth hygiene programmes introduced at the Kindergarten age are promising. PMID- 2323459 TI - [Results of the caries prevention program in Godollo. III. Orthodontic studies]. AB - The ratio of dental anomalies is nearly 50% which corresponds to the value 40 to 60% estimated on basis of international statistics. In the examined two years (1986 and 87) the deep and open bite was more seldom with the elderly age group while toth jam and canine ectopy were characteristic of children of 12 years of age. The Angle II anomaly was twice or three times more frequent than the Angle III one. Early recognition and treatment are very important in order to diminish an inclination to second attacks. PMID- 2323460 TI - Improvement of visual field following trabeculectomy for open angle glaucoma. AB - Trabeculectomy was performed in 24 eyes affected by primary open angle glaucoma. Visual fields were measured using automated perimetry preoperatively and in the first, third, sixth and twelfth months after surgery. Significant improvement in visual field occurred in 96% of cases. PMID- 2323461 TI - Clinical and pathological features of chronic glaucoma in north-east Ghana. AB - Of 34 consecutive patients with chronic glaucoma seen in north-east Ghana, 22 (65%) were male and seven (21%) were aged under 40 years. Only 17% of eyes had a visual acuity better than 6/18 at presentation. Sixteen of 23 patients who underwent gonioscopy had PAS of which 13 had positive skin snips for onchocerciasis, compared with two out of seven patients with positive skin snips who had open angle glaucoma (p = 0.003). Of 22 trabecular meshworks examined by light microscopy ten (45%) showed marked melanin pigmentation which was more common in younger patients but did not correlate with onchocerciasis infection. PMID- 2323462 TI - Chronic glaucoma in northern Ghana--a retrospective study of 397 patients. AB - A retrospective study of 397 patients with chronic glaucoma in North-East Ghana seen in 1986/87 showed 71% of the patients to be male and 26% to be aged under 40 years. Fifty two per cent of eyes were already blind (V/A less than 3/60) at presentation. Blindness was associated with younger age at presentation, and greater distance of residence from the hospital. Only 19% of patients undergoing treatment were attending for follow-up at six months. Of those patients treated medically who returned for follow-up at six months only 17% had an intraocular pressure less than 22 mmHg. While of the patients treated surgically 84% of those seen at six months had an IOP below 22 mmHg. PMID- 2323463 TI - Hydroxypropyl methylcellulose in extracapsular cataract surgery with intraocular lens implantation: intraocular pressure and inflammatory response. AB - We studied prospectively the effects of 2% hydroxypropylmethylcellulose (HPMC), instilled in to the anterior chamber during extracapsular cataract extraction with posterior chamber intraocular lens implantation in 122 patients. Significant pressure rise was noted at 12 and 24 hours post-operatively when HPMC was not removed at the end of surgery. This was prevented by washing HPMC from the anterior chamber at the end of surgery, or by using either acetazolamide or a combination of oxyphenbutazone and vitamin C without washing HPMC. There was no difference in intraocular inflammation between controls and the HPMC groups. The group receiving combined oxyphenbutazone and vitamin C had the least, the differences between these two groups being sufficient. PMID- 2323464 TI - The increasing frequency of surgery for cataract. AB - The increasing frequency of cataract operation was investigated by examining the age related cataract extraction rates for Glasgow. Detailed analysis of case records of sample patients over the past decade was carried out to characterise trends in frequency of intraocular lens implantation, age of the patient at operation, preoperative visual acuity and rate of operation on the second eye. Between 1980 and 1987 the rate of cataract operation per thousand increased from 7.1 to 10.5 for patients aged 75 years and over and from 3.6 to 4.2 for those aged 65 to 74 years. There was a marked rise in the number of cataract operations relative to other eye operations between 1977 and 1988, from 19.3% to 37% and this increase was greatest in patients of 70 years and over. The same decade has seen intraocular lens implantation rise from 0% to 94.6% of cataract extractions. Visual acuity data show a significant trend towards operation at a better level of acuity in patients aged 70 years and over (p = 0.028) but not in younger age groups. There was no change in the visual acuity of the fellow eyes and no change in the frequency of operation on the second eye. It appears that cataract surgery is increasing more than can be predicted from the age of the population and this must be recognised in planning the future level of ophthalmology services. PMID- 2323465 TI - Decentration of the posterior chamber lens implant: the effect of optic size on the incidence of visual aberrations. AB - Intraocular lens implant components such as dialling holes can cause disabling symptoms when decentration of the implant places these components in the pupil. In order to investigate the importance of optic size in this context, we studied two groups of consecutive patients who had undergone cataract surgery: one group had received an implant with a 6 mm diameter optic, and the other an implant with a 7 mm diameter optic. We found that there was a significantly higher incidence of implant components such as dialling holes in the pupil in the 6 mm group when compared to the 7 mm group. The incidence of symptoms such as monocular diplopia and glare was marginally but not significantly higher in the 6 mm group. To minimise the risks of symptoms related to dialling holes in the pupil we recommend an implant design that has a large optical clear zone of at least 6 mm. PMID- 2323466 TI - Extracapsular cataract surgery with and without intraocular lens implantation in Fuchs' Heterochromic Uveitis. AB - The results of extracapsular cataract extraction, with or without posterior chamber intraocular lens (IOL) implantation, in Fuchs Heterochromic Uveitis, are reported. Twenty-nine patients underwent 30 operations. Twenty-two patients (73%) obtained a visual acuity of 6/12 or better. Post-operative uveitis or glaucoma were encountered in 13 eyes, including 11 of 20 eyes with IOL implantation (55%), and two of ten eyes without IOL implantation (20%). IOL implantation is a significant additional factor in cataract surgery in patients with FHU. Preoperative risk factors include severe iris atrophy, secondary glaucoma, and severe abnormalities of iris vasculature. IOL implantation is not recommended in these eyes. The routine postoperative use of anti-glaucoma medication is recommended. Long-term postoperative follow-up is important. PMID- 2323467 TI - Micrographic (MOHS') surgery in the management of periocular basal cell epitheliomas. AB - The use of fresh tissue micrographic surgery offers distinct advantages over other currently available forms of treatment in the management of primary and recurrent periocular basal cell epitheliomas. The technique is described and the results of a prospective study of 22 patients are presented. The advantages in terms of both surgery of tumour excision and tissue preservation are discussed. We conclude that micrographic surgery has a definite role to play in the management of certain periocular basal cell epitheliomas. PMID- 2323468 TI - Impaired autoregulation of the retinal vasculature and microalbuminuria in diabetes mellitus. AB - The relationship between microalbuminuria and retinal vessel responses to sustained handgrip contraction was studied in a group of 20 diabetic patients. The diabetics were divided into two groups based on their albumin excretion rates (AER): Group 1 (AER less than or equal to 10 mcg/min) consisted of ten diabetic patients, mean age 55.8 +/- 3.9 years (mean +/- SEM); five IDDM and five NIDDM. Group 2 (AER greater than 10 mcg/min) comprised ten diabetic patients: mean age 56.8 +/- 3.04 years; six IDDM and four NIDDM. Both groups were similar in that there were no significant differences between mean age, type of diabetes, mean duration of diabetes, glycaemic control or mean resting blood pressures. Group 2 diabetics had a higher incidence of autonomic dysfunction than Group 1, based on the results of four standard tests of autonomic nerve function. There were significantly decreased retinal vessel responses to sustained handgrip contraction in Group 2 diabetics (mean arteriolar constriction 0.1 +/- 0.32%, and mean venule constriction 1.0% +/- 0.99%) compared with Group 1 diabetics (mean arteriolar constriction 6.9 +/- 1.69%, and mean venule constriction 4.2 +/- 0.05%). Retinopathy was slightly worse in Group 2. The implications of the association of microalbuminuria (AER greater than 10 mcg/min) and loss of retinal vessel reactivity to sustained handgrip contraction are discussed. PMID- 2323469 TI - The effect of cervical sympathectomy on retinal vessel responses to systemic autonomic stimulation. AB - The retinal vessel calibre responses to systemic sympathetic stimulation, were studied in nine patients (eight male; mean age: 31.7 years; range: 19-58 years) with unilateral disruption of their cervical sympathetic tract. All patients had ipsilateral decreased/absent facial sweating and a Horners syndrome, evidence of unilateral sympathetic denervation. Both eyes of each patient were studied and the results were analysed in two groups: the group of nine sympathectomised eyes and the control group of unaffected fellow eyes. During handgrip contraction there was a significant difference in the mean retinal arteriolar constriction (mean +/- SEM) between the group of sympathectomised eyes (4.6 +/- 0.89%) and control eyes (7.1 +/- 1.13%), p less than 0.01. Similarly, there was a significant difference in mean venule constriction during sustained handgrip contraction between the group of sympathectomised eyes (1.5 +/- 0.67%) and control eyes (4.9 +/- 0.98%), p less than 0.05. There was no significant difference in the mean rise in diastolic blood pressure between the two groups: control eyes +27.9 +/- 2.38 mmHg and sympathectomised eyes +27.8 +/- 2.25 mmHg. There was no correlation between the blood pressure and retinal vessel responses in either group. These results suggest that the sympathetic nervous system plays an integral role in retinal blood flow regulation. PMID- 2323470 TI - Visual performance in idiopathic macular holes. AB - Previously published reports on the clinical features of idiopathic macular holes highlight the predilection for post-menopausal women and implicate vitreomacular traction in the aetiology of these lesions. Relatively little attention, however, has been paid to the quality of visual loss in eyes with macular holes. Histological studies of full-thickness macular holes have shown loss of all retinal layers in the area of the hole, and this would be expected to produce a central absolute scotoma of the same diameter. The majority of patients with full thickness holes in this series did not have an absolute scotoma large enough to be detected on the Amsler Chart or when reading. It is suggested that following formation of a macular hole, enlargement may occur without further loss of foveal tissue and without enlargement of the absolute scotoma, due to tangential vitreous traction or contraction of an associated epiretinal membrane. PMID- 2323471 TI - Cephalic radiation and retinal vasculopathy. AB - The retinal vascular complications in patients receiving cephalic radiation for various lesions over a ten year period were reviewed. The incidence of retinopathy was 17% overall, but increased with proximity of the treatment site to the eye, being highest in irradiation of the eye/orbit (85.7%), paranasal sinuses (45.4%) and nasopharynx (36.4%). The risk of retinopathy increased significantly when the total dose of radiation exceeded 3000 cGy. The occlusive vasculopathy and capillary incompetence which were the most clinically important features of radiation retinopathy may be exacerbated by pre-existing diabetes. Radiation retinopathy has a long latency and may not be clinically detectable for eight years or more. Long follow-up times with sequential fundoscopy should increase early detection and optimise treatment with laser photocoagulation. PMID- 2323472 TI - Adult vitelliform macular dystrophy. AB - Adult vitelliform macular dystrophy was first described by Gass as giving rise to bilateral, round or oval, yellow, symmetrical, subretinal lesions typically one third to one-half disc diameter in size. Although Gass proposed that this was an autosomal dominant disease, doubt has been expressed as to whether or not it is heritable. We investigated the families of 12 patients who presented to our clinic with foveal lesions typical of adult vitelliform macular dystrophy and found familial involvement compatible with an autosomal dominant inheritance in ten, although it has not been conclusively proven in all families. In the remaining two patients, no familial involvement was detected, but in neither family were both parents available for examination so that autosomal dominant inheritance could not be ruled out. Over half (14/25) the patients with abnormal fundi were asymptomatic, and most had good visual acuity. However, two had visual acuities of less than 6/18 in both eyes. We conclude that adult vitelliform macular dystrophy is an autosomal dominant disorder, and the term would be best reserved for foveal lesions similar to that described by Gass with a dominant pattern of inheritance. PMID- 2323473 TI - Results and complications of conventional repair of bullous retinal detachment using posterior segment air injection. AB - The aims of this retrospective study were to determine the outcome of retinal detachment repair using the drainage, air injection, cryotherapy and explant surgical sequence ('D-ACE' technique) for bullous retinal detachments and also to identify the complications attributable to the injection of the gas. The D-ACE technique was used to repair 206 detachments over a ten year period of which 138 (67%) were successfully re-attached with a single operation. The sub-group of these patients (n = 66) with bullous retinal detachments who would be considered suitable for repair using the technique of pneumoretinopexy (PR) showed a single operation success rate of 85% after D-ACE. Complications attributable to the gas injection occurred in 18 eyes (8.5%). In only four of these (1.9%) did retinal surgery ultimately fail as a result of complications caused by injection of the gas, which represents 10% of all the failures. The results of this series show that the serious complication rate from injecting air into the vitreous cavity is low and that the success rate for treating relatively uncomplicated bullous retinal detachments using the D-ACE technique compares favourably with the results of other published series using either the D-ACE procedure or pneumoretinopexy. PMID- 2323474 TI - The superior peripheral iridectomy: prevention of pupil block due to silicone oil. AB - Superior peripheral iridectomy has been performed in 40 patients who have undergone silicone oil surgery for retinal detachment and who are aphakic. Only two developed raised intraocular pressure due to pupil block by liquid silicone and in each case the iridectomies seemed to be closed by proliferative membrane rather than the silicone meniscus. This type of iridectomy is particularly suitable in patients requiring intracapsular cataract extraction after previous vitrectomy and silicone oil surgery. PMID- 2323475 TI - Refractive changes in silicone filled eyes. AB - In this study we examined refractive changes of 34 eyes in 34 patients treated with silicone oil injection. Six patients presented with aphakic retinal detachment, another 14 were rendered aphakic after silicone oil injection, one was pseudophakic and 13 were still phakic at the time of writing this report. Silicone oil in the vitreous cavity induced a myopic shift in aphakic eyes and a hypermetropic shift in phakic eyes. This tended to render phakic high myopes and aphakes closer to emmetropia. The resultant refraction was dependent on the shape of the silicone oil bubble inside the eye and influenced by the posture of the patient. In phakic patients the ability to accommodate was markedly reduced. PMID- 2323476 TI - The fractal properties of retinal vessels: embryological and clinical implications. AB - The branching patterns of retinal arterial and venous systems have characteristics of a fractal, a geometrical pattern whose parts resemble the whole. Fluorescein angiogram collages were digitised and analysed, demonstrating that retinal arterial and venous patterns have fractal dimensions of 1.63 +/- 0.05 and 1.71 +/- 0.07, respectively, consistent with the 1.68 +/- 0.05 dimension of diffusion limited aggregation. This finding prompts speculation that factors controlling retinal angiogenesis may obey Laplace's equation, with fluctuations in the distribution of embryonic cell-free spaces providing the randomness needed for fractal behaviour and for the uniqueness of each individual's retinal vascular pattern. Since fractal dimensions characterise how completely vascular patterns span the retina, they can provide insight into the relationship between vascular patterns and retinal disease. Fractal geometry offers a more accurate description of ocular anatomy and pathology than classical geometry, and provides a new language for posing questions about the complex geometrical patterns that are seen in ophthalmic practice. PMID- 2323477 TI - Anterior ischaemic optic neuropathy. Differentiation of arteritic from non arteritic type and its management. AB - Anterior ischaemic optic neuropathy (AION), a common, visually crippling disorder, is discussed, with particular emphasis on differentiating AION due to giant cell arteritis (arteritic AION) from that not due to it (non-arteritic AION). Giant cell arteritis is an ophthalmic emergency because of imminent danger of bilateral total blindness, which is almost always preventable if the disease is quickly identified and treated urgently and aggressively. My studies have revealed that the best means of differentiating arteritic from non-arteritic AION is a combination of information from the following: systemic and visual symptoms of giant cell arteritis, high erythrocyte sedimentation rate and C-reactive protein, early massive visual loss, chalky-white optic disc swelling, associated cilio-retinal artery occlusion, massive non-filling of the choroid on fluorescein fundus angiography and temporal artery biopsy. Management of giant cell arteritis and of arteritic AION is discussed. Current misconceptions about AION are pointed out. PMID- 2323478 TI - The success and survival of repeat corneal grafts. AB - The results of 99 second grafts in individual eyes are reported. The five-year survival of these grafts was 49%. Allograft rejection was responsible for the majority of failures, but recurrence of host disease and endothelial decompensation were also important. Glaucoma was an important complication in 38% of eyes. Only 12 eyes in the series had no significant complication and 18 eyes achieved a corrected visual acuity of 6/12 or better. PMID- 2323479 TI - Vascular changes in peripheral corneal destructive disease. AB - A clinical classification of peripheral corneal destructive disease is presented. These syndromes all start within 2 mm of the limbus and are accompanied by varying degrees of vaso-occlusion of the adjacent limbal vascular networks. Close observation of the configuration, integrity and pattern of the limbal vessels can indicate whether the disease is active, quiescent or brought under control with treatment. PMID- 2323480 TI - Microvascular study of the retrolaminar optic nerve in man: the possible significance in anterior ischaemic optic neuropathy. AB - The morphology of the circle of Haller and Zinn and its variations were examined using methyl-methacrylate microvascular corrosion casting of human orbits obtained at post-mortem. It was found to be an elliptical microvascular anastomosis formed by branches of the medial and lateral para-optic short posterior ciliary arteries. The ellipse was divided into superior and inferior parts by the entry points of these branches into the eye, providing an altitudinal blood supply to the retrolaminar optic nerve. Morphological variations in terms of form, position and branches existed between subjects and between eyes from the same subject. The clinical implications of an elliptical 'circle' of Haller and Zinn providing an altitudinal blood supply to the retrolaminar optic nerve are relevant to the pathogenesis of altitudinal visual field defects in anterior ischaemic optic neuropathy. PMID- 2323481 TI - Microbial keratitis after penetrating keratoplasty. AB - Thirty cases of microbial keratitis after penetrating keratoplasty were reviewed to examine the associated risk factors, the spectrum of pathogens and the prognosis for graft survival and visual outcome. The indications for keratoplasty in this group differed markedly from those for all corneal grafts performed with a much higher incidence of previous microbial keratitis and of herpes simplex keratitis. A positive culture was obtained in 93% of cases and in contrast to microbial keratitis overall, Gram positive organisms predominated particularly streptococcus pneumoniae and staphylococcus aureus. Risk factors identified were loose or broken sutures, graft decompensation and a poor ocular surface environment. There was a poor prognosis for graft survival with only 23% of cases retaining a clear graft. Overall 53% of cases were regrafted. PMID- 2323482 TI - Peculiar ophthalmic proliferations. AB - Six unusual cases diagnosed by various scientific methods are described to highlight the role of the histopathologist in clinical ophthalmology. The first case shows the importance of fast tissue diagnosis to prevent possible radical treatment in a limbal pseudotumour. The second presentation is of a small conjunctival mass with orbital involvement, immunohistochemically a B-cell lymphoma and occurring after a recent testicular tumour. The third patient presented with the rarely described nodular hypersensitivity conjunctivitis (Splendore-Hoeppli reaction) and it is suggested that these ophthalmologically observed asymptomatic lesions are apparently clinically transient so reports may be few because of infrequent biopsy. Pan-uveal melanocytic tumours concurrent with thoracic or abdominal carcinoma are reviewed. DNA flow cytometry could, perhaps, assess those ocular lesions for malignancy. The fourteenth case in the literature of lacrimal sac melanoma and possibly the first by tear seedling is illustrated. Lastly, a paediatric orbital fibrous histiocytoma is a cautionary anecdote with successful outcome. PMID- 2323483 TI - Costing a community based screening programme for the detection of glaucoma. AB - The cost of detecting a case of glaucoma in a community based screening programme was calculated using data from a pilot study on a population aged 50 and over. The cost per screen was estimated at 3.35 pounds with a total cost of 311 pounds per case detected. These estimates include the cost of both the algorithmically based screening programme and the hospital assessment of true and false positives. These costs are considered to compare favourably with the potential costs incurred by paying optometrists to screen high risk groups whilst providing the opportunity to detect over twice the number of cases of occult glaucoma. PMID- 2323484 TI - [63d meeting of the Japan Endocrine Society. Osaka, 17-19 May 1990. Abstracts]. PMID- 2323485 TI - Epidemiology of prostatic cancer. AB - The worldwide incidence of prostatic cancer derived from data published by the Union Internationale contre le Cancer and the International Red Cross Committee has been estimated to be 200,000 new cases each year. Cases occur predominantly in the USA (75 per 100,000) and in northern Europe (40 per 100,000), whereas the incidence is low in Asia. Comparison of clinical series and autopsies confirms the high incidence of cancer in older age groups, although not all cases are seen clinically. Mortality increases more slowly than the incidence of the disease, indicating that diagnosis and treatment are increasingly effective. Aetiological factors remain the subject of much discussion, without any criteria appearing to be dominant. PMID- 2323486 TI - Pathophysiologic and endocrine aspects. AB - Androgens regulate development and functional maturation of the prostate. A lack of androgens at puberty impairs normal prostate growth and causes regression and atrophy of the gland in adults. Orchidectomy or indirect androgen suppression by hypophysectomy or administration of oestrogens reduces prostatic weight and secretion. As far as prostatic cancer is concerned, significant improvement occurs in the clinical conditions of patients affected by advanced neoplasia subjected to castration or oestrogen administration. Recently, other endocrine manipulations have been proposed, but the response to these treatments strictly depends on the composition of the neoplastic population. Prostatic cancer consists of cells that are sensitive to or dependent on hormones and others that are hormone-independent. Biological activity of hormones, particularly androgens, is mediated via intracellular receptors, which are not easy to measure in prostatic tissue. Androgen receptor level can be modulated in prostatic cancer cells by natural interferon-beta, opening new perspectives in the therapy of prostatic cancer. PMID- 2323488 TI - American Diabetes Association, 50th annual meeting. June 16-19, 1990, Atlanta, Georgia. Abstracts. PMID- 2323487 TI - Epidermal growth factor and phorbol ester regulate prolactin gene expression via distinct pathways. AB - Previous studies, involving phosphorylation of cytoplasmic proteins and localization of DNA regulatory elements, have suggested that epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) have similar actions on prolactin (PRL) gene expression by pituitary (GH) cells. However, little is presently known about whether the actions of these two factors involve common gene-distal intermediates. In the present study, we have employed two approaches to examine this question. Chronic exposure of GH3 cells to TPA, which strongly down-regulates protein kinase C activity, completely inhibited acute TPA stimulation of transient expression of a transfected PRL promoter construct (( 187)PRL-CAT), but did not inhibit EGF stimulation of either accumulation of endogenous PRL mRNA or of expression of (-187)PRL-CAT. Furthermore, the acute stimulatory effects of EGF and TPA on expression of (-187)PRL-CAT were additive. Each of these observations implies that EGF and TPA have gene-distal actions on PRL gene expression that are at least partially non-overlapping. PMID- 2323489 TI - Self-reported illnesses in family members of alcoholics. AB - This study explores the association between familial alcoholism and the presence of certain conditions in nonalcoholic family members. Depression, obesity, functional bowel syndrome, asthma/emphysema, trauma, and genitourinary problems are conditions suggested by prior studies to be more common in families of alcoholics than in those without an alcoholic family member. Cross-sectional data were collected from a convenience sample of adults in the waiting room of a midwestern, university based family practice clinic. The respondents were classified in two groups: those with little likelihood of familial alcoholism and those with probable familial alcoholism. The groups were matched for race and age, creating two demographically similar groups which were then analyzed as cohorts. The prevalence rates of the conditions of interest in the respondents were calculated in the two groups and compared using the chi-square test for statistical significance. Significant differences in prevalence rates of depression and obesity were found. Trends were found for differing rates of functional bowel syndrome and asthma/emphysema. No differences were found for trauma and genitourinary problems. If differences in disease prevalence truly exist between family members of alcoholic and nonalcoholic individuals, this awareness could enhance the diagnosis and treatment of the conditions of interest in the nonalcoholic relative as well as the alcoholic individual. Family members could be a powerful screening tool for alcoholism. PMID- 2323490 TI - Determinants of adjustment for children of divorcing parents. AB - Family physicians frequently see children and parents when they are adjusting to marital separation. This study examined how well child adjustment at school could be determined from an assessment of interspousal relations, maternal functioning, and child perception variables. Teachers evaluated adaptive functioning, social withdrawal, and aggressive behavior at school for a carefully selected sample of 22 boys and 24 girls (ages 7-12) whose parents had been separated for two to 18 months. Regression analyses indicated that boys' overall school adjustment was associated with better maternal parenting skills, lower child fear of abandonment, less blaming of father for the separation, and positive parental verbal attributions toward the other parent. Girls with better overall school adjustment reported less blaming of their mothers and a higher rate of positive attributions by mother about father. These findings suggest concepts family physicians can use in working with families to minimize the effect of divorce on children. PMID- 2323491 TI - Radiology in family practice: a prospective study of 14 community practices. AB - This study prospectively examined x-rays obtained in the offices of 14 family physicians who read all their own office x-rays and then select those they want a radiologist to read. Each physician completed a standardized report form for 100 consecutive x-rays or for all x-rays obtained for three months, whichever came first. A total of 1,127 x-rays were evaluated. The results indicate that: 1) 86.5% of all x-rays were of three types (chest x-ray, 50.8%; upper extremity, 18.9%; lower extremity, 16.8%); 2) 85.3% of all x-rays were obtained to: a) confirm a clinical diagnosis, b) establish a diagnosis, c) screen for potential problems; 3) 84.8% of the referred x-rays were referred to a) confirm the family physician's interpretation, b) interpret equivocal findings, c) provide medicolegal support, d) improve interpretation skills; 4) the referral rate to a radiologist was 11.6%, with chest x-rays referred most frequently; 5) the same five major ICD-9-CM diagnostic categories were associated with 90.1% of all x rays obtained and 86.5% of all x-rays referred; 6) the types of x-rays obtained in community practice and in a previously studied residency training practice were similar; 7) 55.6% of office x-rays were read as "normal;" and 8) the family physicians' discordancy rate with the radiologists on referred films was 12.5%. PMID- 2323492 TI - The use of key informant networks in assessment of community health. AB - Program planning requires the acquisition of current, reliable information to accurately define the need for the program and to aid in developing its basic structure. In a time of financial restraint, a cost- and time-efficient method for collecting information for program development is important. This paper presents a strategy, borrowed from anthropology, that develops a network of key individuals in the community as a source of information and as a potential resource in program development. The effectiveness of this approach as a method for data collection is illustrated through application to a health and medical needs assessment of a geriatric population. A community diagnosis of this population was obtained. PMID- 2323493 TI - NAPCRG abstracts 1977-1987: analysis of research designs and methods. AB - Research techniques reflect the approach of a discipline to the issues it faces. The annual North American Primary Care Research Group (NAPCRG) meeting has been a forum for family medicine research since 1973. A cross-sectional content analysis was conducted on all 1,295 printed NAPCRG abstracts from 1977 to 1987, classifying the research design and methods. The number of abstracts per meeting increased from 58 in 1977 to 149 in 1987. The predominant research design was cross-sectional (58%), followed by prospective (15%), experimental (15%), and retrospective (3%). The major methods were surveys (34%), chart reviews (24%), or surveys combined with chart reviews (7%). One fourth of all abstracts were cross sectional surveys. NAPCRG research designs and methods have not changed substantially during these 11 years. PMID- 2323494 TI - Entry of US medical school graduates into family practice residencies: 1989-1990 and nine-year summary. AB - This is the ninth report prepared by the American Academy of Family Physicians on the percentage of each medical school's graduates who entered family practice residency programs. Approximately 10.8% of the 15,646 graduates of United States medical schools between July 1988 and June 1989 were first-year residents in family practice in October 1989. This compares to 10.7% in the previous year. The West North Central region reported the highest percentage of medical school graduates who are first-year residents in family practice programs in October 1989; the Middle Atlantic and New England regions continued with the lowest percentages. Medical school graduates from publicly funded medical schools were twice as likely to be first-year residents in family practice in October 1989 than were graduates from privately funded schools. The percentages for each medical school have varied substantially from year to year in the nine years that the AAFP has reported this information. The average percentage for each medical school for the last nine years, as well as the cumulative percentage for each medical school, are reported. PMID- 2323495 TI - A process for evaluation of residency rotations. AB - An evaluation tool for measuring the experiences of family practice residents as they rotate through various services was developed and tested. The tool is described and the effect on the program is discussed. The ease of administration has led to acceptance in not only the family practice program but also in other departments. PMID- 2323496 TI - Teaching prevention by debate. AB - Developing the knowledge and skills of critical appraisal is key to family practice. An innovative course in health promotion/illness prevention which employs a debate format is described. The long-range goal is for family practice residents to be able to weigh evidence where authorities are in conflict in order to incorporate prevention appropriately into their office practices. PMID- 2323497 TI - Resident behaviors during observed pelvic examinations. AB - The pelvic exam is a procedure frequently complicated by difficult communication, sexual tension, and iatrogenic pain. Observations of family practice residents performing pelvic exams were done to identify ways in which they deal with these issues. Among the majority of residents, there was a failure to identify and deal with patients' discomfort. Several episodes of behavior felt to be dysfunctional to the doctor-patient relationship were observed. Implications of these findings for medical education are discussed. PMID- 2323498 TI - Universal health care topic of town forum. PMID- 2323499 TI - Further study of pharyngitis urged. PMID- 2323500 TI - Training in flexible sigmoidoscopy. PMID- 2323501 TI - The feminization of American medicine. PMID- 2323503 TI - American Society for Biochemistry and Molecular Biology, the American Association of Immunologists, joint meeting. New Orleans, Louisiana, June 4-7, 1990. Abstracts 1-3659, TU1-TU35, indexes. PMID- 2323502 TI - Misconduct in science. PMID- 2323504 TI - Colorectal adenomas in the Lynch syndromes. Results of a colonoscopy screening program. AB - Forty-four asymptomatic putative Lynch syndrome patients participated in a colonoscopy screening program. There were 18 men and 26 women; mean age was 44 yr. Thirty percent of Lynch syndrome patients had at least one adenoma; 20% had multiple adenomas. In 18% of the patients, adenomas were discovered proximal to the splenic flexure. In a reference group of 88 age- and sex-matched patients, 11% had adenomas, 4% had multiple adenomas, and 1% had right-sided adenomas. Twenty-one Lynch syndrome patients had follow-up colonoscopies. Of 7 patients with adenomas on initial examinations, 6 had adenomas at follow-up. Of 14 patients with negative initial examination results, 3 had adenomas at follow-up. The prevalence of adenomas in the Lynch syndromes is greater than in an unselected reference group. The adenomas are more proximally located, corresponding to the site of cancer distribution in the Lynch syndromes. A high rate of synchronous and metachronous lesions is found. Our findings support the hypothesis that adenomatous changes are the premalignant lesion in the Lynch syndromes. We also found evidence of heterogeneity among Lynch syndrome families in adenoma incidence. PMID- 2323505 TI - Effect of cigarette smoking on recurrence of Crohn's disease. AB - The effect of cigarette smoking on recurrence (defined in this study as the need for repeat surgery) in patients who had previously required surgery for Crohn's disease was assessed in a historical cohort of 174 patients. Mean follow-up was 10.8 yr. The 5- and 10-yr recurrence rates were 28% and 56%, respectively. Five- and 10-yr rates were significantly different for smokers (36%, 70%) and nonsmokers (20%, 41%). When patients were stratified by gender, the increased risk was more apparent in women (odds ratio 4.2, 95% confidence interval 2.0-4.2) than in men (odds ratio 1.5, 95% confidence interval 0.8-6.0). Evidence for a dose-response relationship could be identified in women but not men. Cigarette smoking may not only be a risk factor for development of Crohn's disease but also may influence disease activity following surgery. PMID- 2323506 TI - Villous atrophy, crypt hyperplasia, cellular infiltration, and impaired glucose Na absorption in enteric cryptosporidiosis of pigs. AB - Intestinal morphology and fluid and electrolyte transport were examined in a neonatal porcine model of cryptosporidiosis. Sections of jejunum, ileum, and colon were obtained for morphometric analysis on days 3, 6, 9, and 12 postinfection, and in vivo perfusion studies of jejunum and ileum were conducted on days 3 and 4 postinfection. The most severe morphologic lesion was seen in the ileum on day 3, and consisted of villous atrophy, crypt hyperplasia, and cellular infiltration. Villous surface area was reduced from 2.1 +/- 0.4 x 10(5) microns2 in control ileum to 0.8 +/- 0.1 x 10(5) microns2 in infected ileum, a result associated with enterocytes that were fewer in number and reduced in cross sectional area. Conversely, the number of inflammatory cells in the lamina propria of the villus increased from 456 +/- 116 in control to 1014 +/- 187 in infected villus without a significant change in the volume of the lamina propria. At the height of infection, there was an approximate 1:2 ratio of both organisms and inflammatory cells to villous enterocytes. In contrast, organisms were not observed in the crypts, and the concentration of inflammatory cells in crypt lamina propria was unaltered. Disappearance of organisms and polymorphonuclear cells from the ileum was associated with restoration of normal structure and was complete by day 12. Although organisms were seen in the colon, the general architecture was not severely affected. On days 3 and 4 postinfection, there was a complete impairment of the glucose-stimulated Na and water absorption in both jejunum and ileum of infected pigs; however, absorption of electrolytes and water from a basic Ringer's solution, in the absence of glucose, was not significantly affected. These results are consistent with a malabsorptive diarrheal disease associated with the morphological damage and are very similar to those seen in enteric viral disease in pigs, except that the upper intestine is more severely affected in the latter. PMID- 2323507 TI - Water contamination and esophageal cancer at Gassim Region, Saudi Arabia. AB - Between January 1980 and December 1982, 183 patients with histologically confirmed carcinoma of the esophagus who were referred to a tertiary referral hospital were studied. Thirty-two (17%) patients were referred from Gassim Region at the north central part of Saudi Arabia. In contrast, only 5% of total cancer patient referrals were from this area. A case-control study showed a significant regional difference within Saudi Arabia and the most referrals from Gassim area. A prospective case-control study showed persistently high numbers of referrals from that region during 1983-1987. When patients from Gassim Region were compared with those referred from other locations, no statistical differences were noted between the two groups except for the source of drinking water. Water analysis from Gassim area showed a high solid content with elevated levels of calcium, magnesium, and to a lesser extent, chromium iron, cadmium, and cobalt. Traces of petroleum oil were found in five of six water samples from Gassim during 1983, compared with 3 of 49 samples from other areas. Mutagenicity tests on water specimens form Gassim Region indicated the presence of possible carcinogens. It is being suggested that the high prevalence of esophageal cancer in this region may be related to contamination of water by impurities such as petroleum oils. Malnutrition, particularly vitamin A deficiency, as well as other factors may have promoted such malignancies. PMID- 2323508 TI - Effects of stimulation of vesical afferents on colonic motility in cats. AB - The effects of distension and isovolumetric contraction of urinary bladder on colonic motility were studied in anesthetized cats. Distension and contraction of the urinary bladder induced an inhibition of spontaneous colonic electromyographic activity and a decrease in the amplitudes of the excitatory junction potentials evoked in the colon by stimulation of the distal end of the parasympathetic nerve fibers. This inhibition was blocked by guanethidine and phentolamine. Reversely, vesical emptying resulted in an increase in colonic motility, abolished by atropine, and an increase in the amplitude of the excitatory junction potentials. Both excitatory and inhibitory reflexes disappeared after hexamethonium. The inhibitory effects of bladder distension were abolished by bilateral section of the lumbar ventral or dorsal spinal roots and after bilateral section of the lumbar colonic or hypogastric nerves. These results indicate (a) that the vesical afferents responsible for the inhibitory and excitatory reflexes run in the hypogastric and pelvic nerves respectively and (b) that the inhibitory and excitatory effects are caused by the activation of sympathetic and parasympathetic efferent nerve fibers, respectively. The supraspinal nervous structures were not implicated in these reflexes because they persisted in spinal cats. PMID- 2323509 TI - Gastroduodenal motility during the delayed gastric emptying induced by cold stress. AB - We have assessed the changes in gastroduodenal motility responsible for the delay in gastric emptying produced by cold stress. Antropyloroduodenal pressures were recorded in 7 healthy volunteers, concurrent with scintigraphic measurement of gastric emptying. The manometric assembly incorporated a sleeve sensor located across the pylorus and side holes in the antrum and the duodenum. When approximately 25% of a 100-g 99m Tc-labeled ground beef burger had emptied from the stomach, a standardized cold pressor test was applied. This consisted of 60-s immersions of the left hand in iced water (4 degrees C), with 15-s rest periods between immersions, for up to 20 min. Cold stress was associated with slowed emptying from the total stomach (median, 17% before stress vs. 2% during stress; p less than 0.01) and the proximal stomach (9% before vs. 3% during; p less than 0.01). Retrograde movement of the solid meal from the distal to the proximal stomach was observed in 4 subjects. Cold stress increased the number of isolated pyloric pressure waves (p less than 0.05), and decreased the number of antral (p less than 0.01) and propagated antropyloroduodenal pressure waves (p less than 0.05). Phase 3-like duodenal activity occurred in 2 subjects during the first 5 min of stress; otherwise there was a reduction in the number of duodenal pressure waves during stress (p less than 0.05). Basal pyloric pressure was not elevate before, during, or after stress. We conclude that in addition to the previously reported antral inhibition, cold stress is associated with changes in pyloric and duodenal motility and, in some subjects, in the intragastric distribution of food. These modifications in gastroduodenal motility are likely to contribute to the delay in gastric emptying produced by this stimulus. PMID- 2323510 TI - The carbohydrate composition of mucin in colonic cancer. AB - Mucins synthesized in colonic cancer are known to be different from those in the normal colon; however, the biochemical differences between these mucins have not been defined. We have purified mucins from samples of nonneoplastic (normal) human colon and colon cancer and found that the carbohydrate content of the cancer-associated mucins is 48% of that in the normal colon, including significant reductions in galactose, N-acetylglucosamine, N-acetylgalactosamine, and fucose. By subjecting the mucins to alkaline degradation, we determined that there are 19% fewer oligosaccharide chains per milligram of cancer-associated colonic mucin than there are in mucins from normal colons. We also found a reduction in mean oligosaccharide chain length in cancer-associated mucin (5.83 carbohydrate residues per chain) compared with those derived from normal colons (10.2 residues). Total and individual amino acid contents were greater in cancer associated mucins, with the exception of three amino acids (threonine, serine, and proline), two of which represent the O-linked glycosylation sites for glycoproteins. Thus, mucins are aberrantly glycosylated in colon cancer, both in terms of the number and mean chain length of the oligosaccharide moiety. Because of their relative abundance in colonic tissue, mucins appear to be useful molecular species in the study of the derangements in protein glycosylation that occur during neoplasia. PMID- 2323511 TI - Tolerance for rectosigmoid distention in irritable bowel syndrome. AB - Two hypotheses were tested: (a) lowered tolerance for balloon distention of the rectosigmoid in patients with irritable bowel syndrome is caused by a psychological tendency to exaggerate the painfulness of any aversive stimulus, and (b) contractions elicited by balloon distention are responsible for pain reports. Tolerance for stepwise distention of a balloon in the rectosigmoid was compared with tolerance for holding one hand in ice water in 16 irritable bowel patients, 10 patients with functional bowel disorder who did not satisfy restrictive criteria for irritable bowel, 25 lactose malabsorbers, and 18 asymptomatic controls. Contractile activity was measured 5 cm above and 5 cm below the distending balloon. Psychometric tests were used to assess neuroticism, anxiety, and depression, and a standardized psychiatric interview was administered. Patients with irritable bowel syndrome had significantly lower tolerance for balloon distention but not ice water, and balloon tolerance was not correlated with neuroticism or other psychological traits measured. Rectosigmoid and rectal motility were also not related to tolerance for balloon distention. Both hypotheses were rejected. A peripheral mechanism such as altered receptor sensitivity may be the cause of distention pain in irritable bowel syndrome. PMID- 2323512 TI - Perception and reflex relaxation of the stomach in response to gut distention. AB - Acute intestinal distention in dogs induces a gastric relaxatory reflex. Our aim was to investigate this reflex in humans, including its relationship to perception. In 9 fasting healthy volunteers, we performed graded balloon distentions (2.5 min duration at 10-min intervals) of either the antroduodenal junction (n = 6) or the distal duodenum (n = 6). Gastric tone was quantified as changes in the volume of air within an intragastric bag maintained at a constant pressure by an electronic barostat. Perception was scored by a graded (0-6) questionnaire. Distention of the antroduodenal junction induced dose-related gastric relaxatory responses: distention at a level producing significant perception (5.0 +/- 0.1 perception score) induced significant relaxation (203 +/- 39 ml change in intragastric volume; p less than 0.05); lower levels of distention still induced relaxation (113 +/- 30 ml change in volume; p less than 0.05) without significant perception (1.0 +/- 0.5 perception score). In the distal duodenum, distention at the threshold for discomfort (5.1 +/- 0.3 perception score) induced significantly smaller gastric relaxatory responses (42 +/- 17 ml change in volume). Distentions below the level of significant perception (1.5 +/- 0.7 perception score) failed to induce gastric responses (14 +/- 15 ml change in volume). These data indicate that both perceived and unperceived gastric relaxatory reflexes in response to distention exist in humans and that these reflexes are region dependent. PMID- 2323513 TI - Biosynthesis of alkaline phosphatase during differentiation of the human colon cancer cell line Caco-2. AB - The human colon cancer cell line Caco-2 undergoes spontaneous enterocytic differentiation during growth and expresses a number of brush-border membrane associated hydrolases typical of a differentiated phenotype. Among these is the enzyme alkaline phosphatase, which is frequently used as a marker of cell differentiation in colon cancer cells. Since the biochemical processes regulating the expression of alkaline phosphatase during cell differentiation are only poorly understood, we examined the biosynthesis and processing of alkaline phosphatases in undifferentiated (0-day confluent) and differentiated (14-day confluent) Caco-2 cells. It was found that both cell phenotypes expressed a single, heat-labile intestinal-like enzyme, which undergoes similar post translational processing and glycosylation. Although the rate of enzyme synthesis and alkaline phosphatase messenger ribonucleic acid was 5-6-fold higher in differentiated cells, the degradation rates in both cell types were similar with a half-life of approximately 10 days. These results suggest that the increase in alkaline phosphatase activity during Caco-2 cell differentiation is caused by changes in the synthetic rate and that the low turnover rates facilitate accumulation of the enzyme. Furthermore, these studies demonstrate that Caco-2 cells are useful for examining the molecular and biochemical events involved in the differentiation of the small intestinal epithelium. PMID- 2323514 TI - Prolonged ambulant recordings of small bowel motility demonstrate abnormalities in the irritable bowel syndrome. AB - Continuous 72-h recordings of duodenojejunal contractile activity were obtained from 20 freely ambulant subjects; pressure was detected by two strain-gauge sensors incorporated in a transnasal catheter attached to an encoder and a miniature tape recorder. The subjects were 12 patients with irritable bowel syndrome, 6 of whom were constipation predominant and 6 of whom were diarrhea predominant, and 8 healthy controls. The procedure was well tolerated by all subjects and did not interfere with sleep or normal activity. In all subjects, the diurnal migrating motor complex cycle was characterized by a brief phase 1 and a prolonged phase 2; this was reversed during sleep when phase 2 was virtually absent. All subjects showed a circadian variation in migrating motor complex propagation velocity, and there was no difference in the patterns of motor activity during sleep between any of the groups. During the day, the duration of postprandial motor activity was shorter in irritable bowel syndrome patients than in controls, and diurnal migrating motor complex intervals were shorter in diarrhea-predominant than in constipation-predominant irritable bowel syndrome. In 11 of 12 inflammatory bowel syndrome patients, episodes of clustered contractions recurring at 0.9-min intervals were noted; these episodes had a mean duration of 46 min and were often associated with transient abdominal pain and discomfort. In both groups of irritable bowel syndrome patients, defecation was significantly (p less than 0.01) prolonged with a greater number of voluntary abdominal contractions (p less than 0.01) than in controls. Prolonged ambulant monitoring of proximal bowel motor activity in subjects who are free to move, eat, and sleep as they choose has, for the first time, clearly defined the striking difference in motility between the sleeping and waking state and shown that abnormalities associated with irritable bowel syndrome are confined to the latter. PMID- 2323515 TI - Effects of dietary lipids on recovery from mucosal injury. AB - The present studies were conducted to determine if diets containing a large amount of fat stimulate the regeneration of damaged intestinal mucosa in the presence or absence of essential fatty acid deficiency. To simulate injury, male Sprague-Dawley rats were given methotrexate, 2.5 mg/kg body wt, subcutaneously for 3 consecutive days. Twenty-four hours after the last methotrexate injection, rats were placed on diets containing either 0%, 1%, or 10% safflower oil. Mucosal weight, protein, deoxyribonucleic acid, maltase, sucrase, lactase, alkaline phosphatase, leucine aminopeptidase, and fatty acids were all determined 3 and 12 days after methotrexate. Crypt-cell production rates were also determined. Essential fatty acid deficiency was confirmed in the 0% safflower oil group, in which triene-tetraene ratios were greater than 0.4. Mucosal weight, deoxyribonucleic acid, protein content, and villus height were all greater in the 1% safflower oil group than in the 0% group at 12 days. In the ileum, 1-h thymidine incorporation was greater in the 0% safflower oil group than in the other two groups. No differences in any of the parameters studied were observed between the 1% and 10% groups. These results suggest that diets deficient in essential fatty acids may impair the recovery of intestinal mucosa from injury. PMID- 2323516 TI - Gastrointestinal manifestations of mixed connective tissue disease. AB - We examined the gastrointestinal tract abnormalities in 61 patients with mixed connective tissue disease. The first 34 were part of a prospective longitudinal study that included manometric and radiographic evaluation of the esophagus. Heartburn (48%) and dysphagia (38%) were by far the most common gastrointestinal symptoms. Seventeen percent of patients undergoing manometry had distal esophageal aperistalsis, and 43% low-amplitude peristalsis (less than 30 mmHg). Studies in 10 patients before and after treatment suggested that esophageal dysfunction in mixed connective tissue disease may be responsive to corticosteroids. Upper esophageal sphincter hypotension was also common. One patient had marked upper esophageal sphincter hypotension and recurrent aspiration, which resolved with corticosteroid therapy. Findings on radiographic studies of the stomach and small bowel in 54 patients and barium enemas in 16 patients were reviewed. Our series included one case each of malabsorption, colonic and small bowel perforations due to vasculitis, chronic active hepatitis, and acute pancreatitis. In conclusion, any area of the gastrointestinal tract may be affected by mixed connective tissue disease, although the esophagus is the most common location. The gastrointestinal aspects of mixed connective tissue disease overlap with those of progressive systemic sclerosis, polymyositis, and systemic lupus erythematosus. PMID- 2323517 TI - Rectal administration of nonsteroidal antiinflammatory drugs. Effect on rat gastric ulcerogenicity and prostaglandin E2 synthesis. AB - Oral administration of nonsteroidal antiinflammatory drugs induces gastroduodenal mucosal damage in experimental animals as well as in humans. The aim of the present study was to evaluate the effect of rectally administered nonsteroidal antiinflammatory drugs on gastric mucosal damage, as well as on mucosal prostaglandin E2 synthesis. Fasting male rats were treated intrarectally with 0.5 ml 1% NaHCO3 solution containing several concentrations of either indomethacin, aspirin, ibuprofen, diclofenac, ketoprofen, or sulindac and concomitantly received 1 ml of 150 mM HCL intragastrically. Control rats received intrarectally the vehicle only. After 4 h, lesions in the secretory part of the stomach were scored and mucosal prostaglandin E2 synthesis was determined by the ex vivo prostaglandin generation technique. Dose-dependent mucosal damage was observed in indomethacin- and diclofenac-treated rats. Ketoprofen damage did not show dose dependency. In sulindac- and aspirin-treated rats, as well as in controls, no damage was detected. All drugs induced a significant and comparable degree of inhibition of prostaglandin E2 synthesis. There was no correlation between the severity of the mucosal damage and the inhibition of prostaglandin E2 synthesis. The ulcerogenicity of rectally administered nonsteroidal antiinflammatory drugs is therefore not directly related to the degree of inhibition of prostaglandin E2 synthesis and is probably related to the specific chemical and pharmacokinetic properties of each individual drug. PMID- 2323518 TI - Surface hydrophobicity of gastric mucosa in peptic ulcer disease. Relationship to gastritis and Campylobacter pylori infection. AB - The hydrophobicity of biopsy specimens of gastric mucosa in 228 dyspeptic subjects undergoing diagnostic endoscopy was assessed by measuring the plateau advancing contact angle of saline drops using a goniometer. Subjects with duodenal ulcers (n = 49) and gastric ulcers (n = 17) had significantly lower mean contact angles than controls (n = 124) without ulcer (57 degrees in duodenal ulcer, 59 degrees in gastric ulcer vs. 66 degrees in controls; p less than 0.0001). There was no change in contact angle after healing with H2-receptor antagonists by comparison with pretreatment (59 degrees vs. 56 degrees for duodenal ulcer, n = 15; 57 degrees vs. 59 degrees for gastric ulcer, n = 5). Controls with gastritis had lower contact angles than those without (61 degrees, n = 50, vs. 70 degrees, n = 63; p less than 0.0001). The presence of Campylobacter pylori was associated with a significant decrease in contact angle in controls (59 degrees, n = 39, vs. 70 degrees, n = 75; p less than 0.0001). PMID- 2323519 TI - The transport of vitamin B12 through polarized monolayers of Caco-2 cells. AB - Caco-2 cells grown on 0.45-micron filters, in Millicell chambers, form intact monolayers with many of the properties of polarized intestinal epithelial cells. It is reported here that these cells bind and internalize intrinsic factor cobalamin complexes and that after 14-28 days in culture this specific binding is exclusively located on the apical membrane. Caco-2 cells also synthesize and secrete a protein with properties similar to transcobalamin II. This protein is secreted from the basolateral side of the cells after 20 days in culture. Specific apical-to-basolateral transcellular transport of [57Co]cobalamin also occurs between 20 and 28 days in culture. Thus, Caco-2 cells provide the first polarized human cell system for studying the transepithelial transport of cobalamin. PMID- 2323520 TI - Gallstone dissolution in vitro using methyl tert-butyl ether: radiologic selection criteria. AB - Methyl tert-butyl ether dissolves cholesterol gallbladder stones when infused through a percutaneous transhepatic catheter. All gallstones, however, contain noncholesterol components that are insoluble in lipid solvents and may be too large to be aspirated through a small catheter or flushed from the gallbladder. To identify which patients have gallstones that are most likely to completely dissolve, we evaluated the ability of methyl tert-butyl ether to dissolve gallstones in vitro based on their radiodensity and size. Radiodensity influenced completeness of dissolution (p less than 0.01), but size did not (p greater than 0.5). Twenty-six of 32 radiolucent stones (81%) dissolved completely, leaving residual debris less than 2 mm in diameter. Only 2 of 32 radiopaque stones (6%) dissolved completely. Insoluble radiolucent and radiopaque stones less than 0.5 cm in diameter were black pigment stones. Four radiolucent and 19 of 22 radiopaque stones (86%) greater than 0.5 cm in diameter underwent partial dissolution leaving residual debris 2 mm or larger. By infrared spectroscopy, calcium bilirubinate and calcium carbonate were identified as the principal components of this methyl tert-butyl ether-insoluble debris. Until methods for dissolving or fragmenting noncholesterol components of gallstones are available, only patients with radiolucent gallstones should be treated with methyl tert butyl ether. PMID- 2323521 TI - Effect of loxiglumide on gallbladder contractile response to cerulein and food in humans. AB - The present study investigated the effect of loxiglumide, a new selective cholecystokinin-receptor antagonist, on the gallbladder contractile responses to caerulein and to food in humans. In 6 healthy men, the gallbladder emptying driven by intravenous infusion of stepwise increasing doses of cerulein (10-80 ng/kg . h) and that induced by a 550-cal standard meal were monitored by ultrasonography. In both sets of experiments, the effect of loxiglumide was tested at various infusional rates against a control infusion of saline. An infusional rate of 2.5 mg/kg . h of loxiglumide abolished the gallbladder response even to maximal doses of cerulein, whereas a rate of 1.0 mg/kg . h counteracted the cholecystokinetic activity of cerulein up to the dose of 20 ng/kg . h. In postprandial experiments, the cholecystokinin antagonist dose dependently inhibited the physiologic gallbladder contraction. The maximal gallbladder emptying, which always occurred 85 min after the meal, was 71.1% +/- 3.3% of basal volume in control studies, 39.2% +/- 1.8% during infusion of 2.5 mg/kg . h of loxiglumide, and 17.3% +/- 5.9% when 5.0 mg/kg . h were infused. A dose of 7.5 mg/kg . h of loxiglumide was able to prevent any postprandial emptying of the gallbladder. The present study shows that a selective cholecystokinin receptorial blockade competitively antagonizes cerulein-induced gallbladder contraction and dose-dependently inhibits postprandial gallbladder emptying. PMID- 2323522 TI - Feedback regulation of human pancreatic secretion. Effects of protease inhibition on duodenal delivery and small intestinal transit of pancreatic enzymes. AB - To determine the effects of luminal protease inhibition on duodenal delivery and the intraluminal fate of pancreatic enzymes, six healthy subjects were intubated with an oro-ileal multilumen tube assembly. By using nonabsorbable markers, cumulative trypsin, chymotrypsin, lipase, and amylase activities were measured as delivered to duodenum, midjejunum, and distal ileum, with or without simultaneous duodenal perfusion of the protease inhibitor camostat at graded doses. Compared with saline, camostat (a) inhibited trypsin activity in the entire small intestinal lumen by up to 99%, and significantly reduced chymotrypsin activity by up to 89%; (b) significantly increased duodenal deliveries of lipase activity, amylase activity and volume; (c) did not influence plasma cholecystokinin concentrations; and (d) significantly increased jejunal and ileal deliveries of lipase but not amylase activity. Small intestinal transit and motility were not affected by camostat. In additional in vitro studies, camostat significantly reduced the spontaneous decline in lipase activity in fresh human duodenal juice incubated at 37 degrees C. These findings demonstrate that duodenal deliveries of lipase and amylase activities increase when intraluminal protease activity is decreased; they suggest that this increase is not caused by slower proteolytic destruction of enzyme protein but by stimulation of pancreatic secretion. Thus, luminal protease-mediated feedback regulation of pancreatic secretion may be operative in humans. Because plasma cholecystokinin concentrations were not affected, these effects may in part be independent of cholecystokinin. The data further suggest that proteolytic digestion plays a major role in the rapid loss of luminal lipase activity on small intestinal transit. PMID- 2323523 TI - Effect of truncal vagotomy on cholecystokinin release, gallbladder contraction, and gallbladder sensitivity to cholecystokinin in humans. AB - The present study was undertaken to investigate the gastric and intestinal phase of stimulation of postprandial gallbladder contraction and endogenous cholecystokinin secretion in patients with truncal vagotomy and pyloroplasty. Gallbladder emptying, measured by cholescintigraphy, and endogenous cholecystokinin secretion, measured by radioimmunoassay, were studied after both intragastric and intraduodenal administration of corn oil. In addition, the gallbladder responsiveness to cholecystokinin was investigated by infusion of stepwise increasing doses of exogenous cholecystokinin. In the 6 patients with truncal vagotomy, plasma CCK and gallbladder responses to intraduodenal fat were significantly delayed compared to normal subjects. In contrast, the onset of the plasma cholecystokinin increase and gallbladder emptying after intragastric fat was significantly earlier in the vagotomized patients compared with the normal subjects. In the normal subjects, plasma cholecystokinin and gallbladder responses to intragastric fat were significantly lower during the first 25 min after stimulation compared with the results after intraduodenal fat, whereas in the patients with truncal vagotomy and pyloroplasty, no differences in plasma cholecystokinin and gallbladder responses were found according to the site of fat stimulation. The gallbladder-emptying response to exogenous cholecystokinin increased significantly in patients who had undergone truncal vagotomy. It is concluded (a) that truncal vagotomy with pyloroplasty influences the timing but not the magnitude of fat-stimulated gallbladder contraction and endogenous cholecystokinin secretion; and (b) that the sensitivity of the gallbladder to endogenous and exogenous cholecystokinin is significantly increased in patients with truncal vagotomy. PMID- 2323524 TI - Dissolution of calcium bilirubinate and calcium carbonate debris remaining after methyl tert-butyl ether dissolution of cholesterol gallstones. AB - Methyl tert-butyl ether rapidly dissolves cholesterol gallstones, although insoluble debris may remain. Total gallstone dissolution could be achieved if safe solvents for these noncholesterol components can be developed. We evaluated the in vitro ability of ethylenediaminetetraacetic acid, citrate, dimethyl sulfoxide, and ionic or nonionic detergents to dissolve the predominantly calcium bilirubinate and calcium carbonate debris remaining after methyl tert-butyl ether gallstone dissolution. Ethylenediaminetetraacetic acid 1% or 2% at pH 9.5 was the most effective of the solvents studied for dissolving calcium and bile pigment. The addition of cholate (25-200 mM) or polysorbate (1%-10%) to ethylenediaminetetraacetic acid 1% at pH 9.5 enhanced pigment dissolution compared to ethylenediaminetetraacetic acid alone. Dissolution of pellets prepared from human gallstones and composed predominantly of either calcium bilirubinate or calcium carbonate was 80% and 85% at 4 h using ethylenediaminetetraacetic acid 1% plus polysorbate-20 1% at pH 9.5. We conclude that ethylenediaminetetraacetic acid, either alone or with a detergent, is an effective solvent for methyl tert-butyl ether-insoluble gallstone debris and deserves assessment in vivo. PMID- 2323525 TI - Hyperviscosity syndrome in a hypercholesterolemic patient with primary biliary cirrhosis. AB - A 45-yr-old woman with primary biliary cirrhosis, xanthomatosis, and marked hypercholesterolemia developed symptoms of the hyperviscosity syndrome on three separate occasions. On presentation, she had a plasma total cholesterol concentration of 53.40 mM (2065 mg/dl) and a relative serum viscosity of 2.9. Following three courses of plasma exchange in a 5-day period, the total cholesterol level decreased to 6.75 mM (261 mg/dl) and the viscosity to 1.3. The cutaneous xanthomata were markedly diminished 1 wk following plasma exchange. Despite therapy with colestipol (30 g/d), the hyperviscosity syndrome developed 147 days later. This cycle recurred again 137 days after colestipol was discontinued. Serum viscosity and total cholesterol concentration were highly correlated during the postexchange or accumulation phases (R = 0.95, 95% CI: 0.85, 0.98) and during the exchange or interventional phases (R = 0.95, 95% CI: 0.84, 0.99). Serum viscosity was less significantly correlated with total serum protein (R = 0.84; 95% CI: 0.55, 0.95) or with plasma triglyceride (R = 0.63; 95% CI: 0.26, 0.81). There were no significant correlations of red cell mass, plasma fibrinogen levels, or serum bile salts with viscosity. Subfractionation of plasma into lipoprotein classes showed 45% of total cholesterol in the lipoprotein X fraction and a presumptive slow alpha-lipoprotein species. It is postulated that both the hyperviscosity syndrome and rapid resolution of xanthomata in the patient may be attributable to the physiology of her abnormal lipoprotein particles. PMID- 2323526 TI - Achalasia due to diffuse esophageal leiomyomatosis and inherited as an autosomal dominant disorder. Report of a family study. AB - Although achalasia is usually of idiopathic origin, it may be secondary to another disease process such as neoplasia. The first description of a familial achalasia syndrome that appears to be secondary to diffuse esophageal leiomyomatosis with entrapment of nerve ganglia is presented. Documented in four generations of a family, the disease followed an autosomal dominant mode of inheritance. Long lower esophageal sphincter pressure zones and a high incidence of epiphrenic diverticula were interesting accompaniments of achalasia in this family. Many achalasia-affected family members have also had associated intestinal leiomyomas or neurofibromas. Affected family members also had urticaria pigmentosa, and some had systemic mast cell disease as well. PMID- 2323527 TI - Cyclosporine in Crohn's disease--low doses won't do it. PMID- 2323528 TI - Endoscopic treatment of colonic angiodysplasia: the procedure was a success, but.... PMID- 2323529 TI - The load-to-length principle in the inhibition of gastric emptying by intestinal feedback. PMID- 2323530 TI - Pathogenesis of duodenal ulcer. PMID- 2323531 TI - Help the patient comply with the colonic prep. PMID- 2323532 TI - Effect of secretin on bile formation. PMID- 2323533 TI - Markers, motility, and mental illness. PMID- 2323534 TI - Comparison of forward and backwards methods of cell cycle analysis. PMID- 2323535 TI - Characteristic new members of the phthiocerol and phenolphthiocerol families from Mycobacterium ulcerans. AB - Diacyl phthiodiolone A and phenolphthiodiolone A lipids were isolated from two strains of Mycobacterium ulcerans. The diol units of the phthiodiolone A and phenolphthiodiolone A components were shown to have erythro stereochemistry by infrared spectroscopy and proton nuclear magnetic resonance of an acetal derivative. This stereochemistry is shared only by related diols from M. marinum, the diols from M. bovis, M. kansasii, M. leprae and M. tuberculosis having threo stereochemistry. PMID- 2323536 TI - Improved methods for the preparation of high molecular weight DNA from large and small scale cultures of filamentous fungi. AB - Improved methods are described for the isolation of pure, high molecular weight DNA from small and large scale cultures of filamentous fungi. The methods depend on the extraction of DNA under conditions which prevent nuclease activity and contamination by carbohydrate. The small scale method depends on enzymatic digestion of the wall whereas the large scale method uses partial damage followed by autolysis. High yields of DNA are obtained by both methods and the DNA is suitable for restriction analysis. Southern Blotting, RFLP analysis, dot blotting and the production of gene libraries. The small scale method can be used for the simultaneous analysis of multiple cultures. PMID- 2323537 TI - Enterotoxigenicity and frequency of Campylobacter jejuni, C. coli and C. laridis in human and animal stool isolates from different countries. AB - Campylobacter jejuni and C. coli strains were collected during three different years from adult patients with enterocolitis in Sweden (n = 372) from 49 patients in Kuwait, and Campylobacter strains from hens from Mexico, Pakistan and Sweden (n = 107) and Swedish pigs (n = 47). C. jejuni was the predominant species in human and hen isolates, and C. coli in pigs C. coli was significantly more common in human isolates from Sweden, and more common in hen isolates from Pakistan, than in hens from Sweden and Mexico. C. laridis was only isolated from pigs (17%) and was in no case enterotoxigenic. Both in human and hen isolates, C. jejuni strains were more enterotoxigenic than C. coli strains. C. jejuni strains from Swedish hens were less enterotoxigenic than those from Pakistan and Mexico (P less than 0.001), and strains from pigs were less enterotoxigenic than those from hens (P less than 0.001). We conclude that C. jejuni are more often enterotoxigenic and possibly more virulent than c. coli and C. laridis. The relative frequency of C. jejuni and C. coli in humans and animals differs from one country to another. PMID- 2323538 TI - Amylase-binding as a discriminator among oral streptococci. AB - The ability of 51 strains, belonging to Streptococcus sanguis, 'S. mitior', S. oralis and related groups, to bind salivary amylase was studied. Most strains were grouped according to their DNA-relatedness and then compared using 14 phenotypic tests. S. mitis, 'S. mitior' and three relatively new groups of strains ('CR', 'MGH' and 'Tufted mitior') bound salivary amylase, while strains of S. sanguis and S. oralis did not. The ability of strains to bind amylase or not was remarkably consistent within groups and the test proved to be reproducible, rapid and easy to perform. Combination of the amylase-binding test with 6 other conventional physiological tests allowed the construction of a dichotomous identification key which correctly identified 95% of strains for which genetic data was available. These findings suggest that the ability of organisms to bind salivary amylase could become a key test in identification schemes for certain oral streptococci. PMID- 2323539 TI - Diisopropylfluorophosphate-binding proteins in the outer membrane of Fusobacterium nucleatum: strain variations. AB - Six strains of Fusobacterium nucleatum were tested for their ability to react with [3H]diisopropylfluorophosphate (DFP), a serine protease inhibitor. Several cytoplasmic proteins were labelled but the strongest labelling was regularly observed in a few outer membrane proteins. The number and the molecular mass of the proteins detected varied according to the strain tested. A 61 kDa protein was labelled in all strains tested, including the two type strains ATCC 10953 and ATCC 25586. A 65 kDa protein was particularly strongly labelled in strains Fev1 and F6. PMID- 2323540 TI - SshAI restriction endonuclease from Salmonella shikmonah. AB - A new type II restriction endonuclease, SshAI, was purified from Salmonella shikmonah TK139 of kangaroo origin. The recognition and cleavage specificity of Ssh AI was determined to be 5'-CC/TNAGG-3', identical to that of SauI from Streptomyces aureofaciens and Bsu36I from Bacillus subtilis. Based on closely related and in part overlapping recognition specificities of Ssh AI and other restriction endonucleases, a close evolutionary relationship is proposed for all known Salmonella restriction endonucleases. PMID- 2323542 TI - Immunoelectron microscopic demonstration that Renibacterium salmoninarum is encapsulated. AB - The cell surfaces of four strains of Renibacterium salmoninarum, including the type strain Lea-7-74T, were examined by transmission electron microscopy after immuno-stabilization and staining with ruthenium red. Cells were covered with a layer of capsular material whose thickness varied between 30 to 60 nm. Our results indicate that R. salmoninarum is encapsulated. PMID- 2323541 TI - Purification and partial characterization of an iron regulated outer membrane protein of B. fragilis under non-denaturing conditions. AB - The CHAPS-PAGE gelsystem we applied gave a good separation of the proteins of Bacteroides fragilis under non-denaturing conditions. We succeeded with preparative CHAPS-PAGE in purifying an iron regulated outer membrane protein (a 44 kDa polypeptide on SDS-PAGE) of B. fragilis. This integral membrane protein proved to be a lipopolysaccharide binding protein with an isoelectric point of approximately pH 5.5. This method of purifying membrane proteins could be an important step in research into the function of membrane proteins. PMID- 2323543 TI - Lysogenic phages of Clostridium perfringens: mapping of the chromosomal attachment sites. AB - The sites of insertion for two lysogenic bacteriophages have been mapped on the chromosome of Clostridium perfringens strain CPN50 using two techniques based on pulsed field gel electrophoresis. Phage phi 29 was mapped to the 1 Mb region of the 3.6 Mb genome, near nanH which encodes a potential virulence factor, while phi 59 was found to have inserted at 2.9 Mb. PMID- 2323544 TI - Virulence of Yersinia ruckeri serotype I strains is associated with a heat sensitive factor (HSF) in cell extracts. AB - Cell extracts of Yersinia ruckeri (serotype I) were examined by SDS-PAGE and Western blotting. An unusual band, termed heat-sensitive factor (HSF) was observed in extracts of virulent strains only. It is thought to be lipid in nature; no differences could be detected in the region of the band in protein profiles of virulent and avirulent strains. When trout were infected either by intraperitoneal injection or bath immersion, mortalities occurred only with HSF+ strains. The HSF appears to be an important virulence determinant of Y. ruckeri. PMID- 2323545 TI - Simplified procedure for purification of Bordetella bronchiseptica dermonecrotic toxin. AB - Bordetella bronchiseptica dermonecrotic toxin was purified by a simplified method. The method consisted of SP Toyopearl 650M chromatography and high performance liquid chromatography on a TSK gel G3000SW column. 47.5% of the activity of the crude cell extract was recovered. The purified toxin behaved as a homogeneous protein in sodium dodecyl sulfate polyacrylamide gel electrophoresis, high performance liquid chromatography, and agar gel double diffusion tests. PMID- 2323546 TI - Heterologous expression of the Bacteroides ruminicola xylanase gene in Bacteroides fragilis and Bacteroides uniformis. AB - A cloned xylanase gene from the ruminal bacterium Bacteroides ruminicola 23 was transferred by conjugation into the colonic species Bacteroides fragilis and Bacteroides uniformis by using the Escherichia coli-Bacteroides shuttle vector pVAL-1. The cloned gene was expressed in both species, and xylanase specific activity in crude extracts was found to be at least 1400-fold greater than that found in the B. ruminicola strain. Analysis of crude extract proteins from the recombinant B. fragilis by SDS-PAGE demonstrated a new 60,000 molecular weight protein. The xylanase activity expressed in both E. coli and B. fragilis was capable of degrading xylan to xylooligosaccharides in vitro. This is the first demonstration that colonic Bacteroides species can express a gene from a ruminal Bacteroides species. PMID- 2323547 TI - Heterologous expression of a mutated toxin gene from Bacillus thuringiensis subsp. tenebrionis. AB - Using oligonucleotide probes we have isolated a DNA fragment encoding an insecticidal toxin of the coleopteran specific Bacillus thuringiensis subsp. tenebrionis. The gene was altered by site directed mutagenesis at its 5'-end and adapted for general cloning and expression purposes with a linker including a start codon and new restriction sites. The constructs were inserted into several vector plasmids and expressed in Escherichia coli. Expression E. coli was strongly enhanced by the lac-promoter. A fusion protein with phage MS2-polymerase was produced together with a 67 kDa protein also found for normal expression of the toxin gene. Synthesis of the latter protein indicated a second ribosome binding site at the 5'-terminus of the toxin encoding sequence. Toxin-containing proteins were identified by Western blot analysis. The positive cell extracts from E. coli had insecticidal activity on larvae of the Colorado potato beetle. The cloned gene is not homologous to a gene previously cloned by us whose gene products were also toxic to coleopteran larvae. PMID- 2323548 TI - Comparative analysis of the hemolysin genes of Vibrio cholerae non-01, V. mimicus, and V. hollisae that are similar to the tdh gene of V. parahaemolyticus. AB - The genes encoding the hemolysins similar to the thermostable direct hemolysin (tdh gene) of Vibrio parahaemolyticus were cloned from chromosomes of V. mimicus and V. hollisae. These cloned hemolysin genes and previously cloned tdh genes of V. parahaemolyticus and V. cholerae non-01 were compared by physical mapping and by hybridization with oligodeoxyribonucleotide probes. The nucleotide sequences in the coding regions of all the cloned hemolysin genes were very homologous and had only minor variations but the sequences flanking the homolysin genes were dissimilar, indicating that the hemolysin genes have a common ancestor and suggesting that they may have been transferred between Vibrio species as a descrete genetic unit. PMID- 2323549 TI - Isolation and characterization of a type II restriction endonuclease from Streptococcus thermophilus. AB - A type II restriction endonuclease Sth134I was isolated from Streptococcus thermophilus strain 134. The enzyme is an isoschizomer of HpaII. The restriction endonuclease is most active at Mg(II) greater than or equal to 5 mM; in the pH range of 7.5-8; temperature of 50 degrees-55 degrees C; and (KCl) or (NaCl) below 100 mM. Double digestion and ligation experiments showed that Sth134I apparently recognized and cleaves DNA at the sequence C1CGG to produce two-base, 5' protruding ends. PMID- 2323550 TI - Purification and analysis of the antigenicity of a 69,000 Da protein from Bordetella pertussis. AB - A purification scheme was devised for a 69-kDa outer membrane protein of Bordetella pertussis, a virulence-associated protein which may play a role in the pathogenesis of the organism. The protein was purified to apparent homogeneity by heating B. pertussis cells for 1 h at 60 degrees C followed by DEAE-Sepharose and Affi-Gel Blue chromatography. Antibodies found in sera obtained from patients diagnosed as having pertussis reacted with this protein. This purification scheme should be useful for the production of the 69 kDa protein which is currently being evaluated as a pertussis vaccine candidate. PMID- 2323551 TI - Production and characterisation of Campylobacter jejuni enterotoxin in a synthetic medium and its assay in rat ileal loops. AB - A synthetic medium for production of Campylobacter jejuni enterotoxin was developed for the purposes of its purification by modifying syncase medium, replacing sucrose with glucose, and supplementing with 0.025% sodium pyruvate, 0.25% sodium metabisulphite, 0.001% ferric chloride and 0.1% L-cysteine, adjusted to pH 6.7. Culture filtrates of a human diarrhoeal and a chicken isolate, grown in this medium caused fluid accumulation ranging between 0.50-0.70 ml/cm of rat ileal loop. The kinetics of toxin production indicated a peak at 36 h and decline by 72 h, coinciding with the period of release of protease by the organism. At least 0.4 rat ileal loop units of enterotoxic activity was recovered per ml of culture filtrates and one unit of this toxin contained only 14 micrograms of protein. The toxin is heat-labile, pH dependent, nonhaemolytic, resistant to trypsin, sensitive to papain and pronase and may show subunit molecular weight analogy with CT subunits. PMID- 2323552 TI - Cloning and characterization of a gene encoding a new thermostable hemolysin from Vibrio parahaemolyticus. AB - A new thermostable hemolysin (delta-VPH) gene was cloned from a Kanagawa-negative Vibrio parahaemolyticus strain into vector pBR322 in Escherichia coli K12. The nucleotide and amino acid sequences had no homology with those of the thermostable direct hemolysin (TDH) which causes the Kanagawa phenomenon, and of the thermolabile hemolysin (TLH) of V. parahaemolyticus. The gene was present in all V. parahaemolyticus strains tested and also in one strain of V. damsela. PMID- 2323553 TI - Pathways of transformation in Ustilago maydis determined by DNA conformation. AB - Ustilago maydis was transformed by plasmids bearing a cloned, selectable gene but lacking an autonomously replicating sequence. Transformation was primarily through integration at nonhomologous loci when the plasmid DNA was circular. When the DNA was made linear by cleavage within the cloned gene, the spectrum of integration events shifted from random to targeted recombination at the resident chromosomal allele. In a large fraction of the transformants obtained using linear DNA, the plasmid DNA was not integrated but was maintained in an extrachromosomal state composed of a concatameric array of plasmid units joined end-to-end. The results suggest the operation of several pathways for transformation in U. maydis, and that DNA conformation at the time of transformation governs choice of pathways. PMID- 2323554 TI - Recent appearance and molecular characterization of mitochondrial DNA deletions within a defined nematode pedigree. AB - The mitochondrial genome of Romanomermis culicivorax, a parasitic nematode of mosquitoes, contains an amplified 3.0-kilobase (kb) locus organized as direct repeats and as noncontiguous, inverted copies. These amplified sequences are actively undergoing rearrangement. One recent event has resulted in a 1133-base pair (bp) deletion located entirely within a single amplified segment. The deletion junction occurs between two imperfect 58-bp repeats, implicating strand pairing in this alteration. A second event has generated mitochondrial DNA (mtDNA) forms differing by a single, intact 3.0-kb repeating unit. By analyzing molecules derived from independently reared subcultures, it appears these new mtDNA forms arose within the last 170 nematode generations. Our results indicate that the occurrence and selection of novel animal mitochondrial genomes can now be studied in this experimentally manipulable nematode system. PMID- 2323555 TI - Genetic analysis of defecation in Caenorhabditis elegans. AB - Defecation in the nematode Caenorhabditis elegans is achieved by a cyclical stereotyped motor program. The first step in each cycle is contraction of a set of posterior body muscles (pBoc), followed by contraction of a set of anterior body muscles (aBoc), and finally contraction of specialized anal muscles that open the anus and expel intestinal contents (Exp). By testing existing behavioral mutants and screening for new mutants that become constipated due to defects in defecation, I have identified 18 genes that are involved in defecation. Mutations in 16 of these genes affect specific parts of the motor program: mutations in two genes specifically affect the pBoc step; mutations in four genes affect the aBoc step; mutations in four genes affect the Exp step; and mutations in six genes affect both aBoc and Exp. Mutations in two other genes affect the defecation cycle period but have a normal motor program. Sensory inputs that regulate the cycle timing in the wild type are also described. On the basis of the phenotypes of the defecation mutants and of double mutants, I suggest a formal genetic pathway for the control of the defecation motor program. PMID- 2323556 TI - Estimates of selection and gene flow from measures of cline width and linkage disequilibrium in heliconius hybrid zones. AB - Hybrid zones can yield estimates of natural selection and gene flow. The width of a cline in gene frequency is approximately proportional to gene flow (sigma) divided by the square root of per-locus selection (square root of s). Gene flow also causes gametic correlations (linkage disequilibria) between genes that differ across hybrid zones. Correlations are stronger when the hybrid zone is narrow, and rise to a maximum roughly equal to s. Thus cline width and gametic correlations combine to give estimates of gene flow and selection. These indirect measures of sigma and s are especially useful because they can be made from collections, and require no field experiments. The method was applied to hybrid zones between color pattern races in a pair of Peruvian Heliconius butterfly species. The species are Mullerian mimics of one another, and both show the same changes in warning color pattern across their respective hybrid zones. The expectations of cline width and gametic correlation were generated using simulations of clines stabilized by strong frequency-dependent selection. In the hybrid zone in Heliconius erato, clines at three major color pattern loci were between 8.5 and 10.2 km wide, and the pairwise gametic correlations peaked at R approximately 0.35. These measures suggest that s approximately 0.23 per locus, and that sigma approximately 2.6 km. In erato, the shapes of the clines agreed with that expected on the basis of dominance. Heliconius melpomene has a nearly coincident hybrid zone. In this species, cline widths at four major color pattern loci varied between 11.7 and 13.4 km. Pairwise gametic correlations peaked near R approximately 1.00 for tightly linked genes, and at R approximately 0.40 for unlinked genes, giving s approximately 0.25 per locus and sigma approximately 3.7 km. In melpomene, cline shapes did not perfectly fit theoretical shapes based on dominance; this deviation might be explained by long-distance migration and/or strong epistasis. Compared with erato, sample sizes in melpomene are lower and the genetics of its color patterns are less well understood. In spite of these problems, selection and gene flow are clearly of the same order of magnitude in the two species. The relatively high per locus selection coefficients agree with "major gene" theories for the evolution of Mullerian mimicry, but the genetic architecture of the color patterns does not. These results show that the genetics and evolution of mimicry are still only sketchily understood. PMID- 2323557 TI - Genetic differences in the duration of the lymphocyte heat shock response in mice. AB - Lymphocytes from adult mice bearing a known difference in genetic susceptibility to teratogen-induced exencephaly (SWV/SD, and DBA/2J) were evaluated for changes in protein synthesis following an in vivo heat treatment. Particular attention was paid to changes indicative of the heat shock response, a highly conserved response to environmental insult consisting of induction of a few, highly conserved proteins with simultaneous decreases in normal protein synthesis. The duration of heat shock protein induction in lymphocytes was found to be increased by 1 hr in the teratogen-sensitive SWV/SD strain as compared to the resistant DBA/2J strain. Densitometric analysis revealed a significant decrease in the relative synthesis of at least two non-heat shock proteins (36 kD and 45 kD) in the SWV/SD lymphocytes as compared to DBA/2J cells. The increased sensitivity of protein synthesis to hyperthermia in the SWV/SD lymphocytes were lost in the F1 progeny of reciprocal crosses between SWV/SD and DBA/2J mouse strains. Sensitivity to hyperthermia-induced exencephaly is recessive to resistance in these crosses. The relationship between altered protein synthesis and teratogen susceptibility is discussed. PMID- 2323558 TI - Molecular cloning and genetic mapping of the t complex responder candidate gene family. AB - Male transmission ratio distortion (TRD) is a property of mouse t haplotypes requiring the t complex responder locus (Tcr). Tcr maps to the central region of t haplotypes, and is embedded within a series of large duplicated tracts of DNA known as "T66 elements." In previous work, a family of genes (the "T66" genes) was identified within this region that encodes male germ cell-specific transcripts. Genetic and molecular data indicate that one of these genes represents Tcr. Here, we describe the molecular cloning of the four members of the T66 gene family, the genetic mapping of these genes to three adjacent t haplotype loci, and comparative restriction enzyme analysis of the genes. The results indicate that these genes are highly similar to one another, and were created by recent, complex duplication events. This suggests that a minor alteration(s) could have been responsible for conferring "mutant" responder activity upon Tcr, while the other homologs retained "wild-type" biochemical function. In addition, we have identified and mapped three T66 genes in wild-type t complexes. They reside in two separate loci at the opposite ends of the proximal t complex inversion, and are separated by at least 3 cM. PMID- 2323559 TI - Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. AB - To explain the long-term persistence of polymorphic alleles (trans-specific polymorphism) at the major histocompatibility complex (MHC) loci in rodents and primates, a computer simulation study was conducted about the coalescence time of different alleles sampled under various forms of selection. At the same time, average heterozygosity, the number of alleles in a sample, and the rate of codon substitution were examined to explain the mechanism of maintenance of polymorphism at the MHC loci. The results obtained are as follows. (1) The coalescence time for neutral alleles is too short to explain the trans-specific polymorphism at the MHC loci. (2) Under overdominant selection, the coalescence time can be tens of millions of years, depending on the parameter values used. The average heterozygosity and the number of alleles observed are also high enough to explain MHC polymorphism. (3) The pathogen adaptation model proposed by Snell is incapable of explaining MHC polymorphism, since the coalescence time for this model is too short and the expected heterozygosity and the expected number of alleles are too small. (4) From the mathematical point of view, the minority advantage model of frequency-dependent selection is capable of explaining a high degree of polymorphism and trans-specific polymorphism. (5) The molecular mimicry hypothesis also gives a sufficiently long coalescence time when the mutation rate is low in the host but very high in the parasite. However, the expected heterozygosity and the expected number of alleles tend to be too small. (6) Consideration of the molecular mechanism of the function of MHC molecules and other biological observations suggest that the most important factor for the maintenance of MHC polymorphism is overdominant selection. However, some experiments are necessary to distinguish between the overdominance and frequency dependent selection hypotheses. PMID- 2323560 TI - Analysis of the inheritance, selection and evolution of growth trajectories. AB - We present methods for estimating the parameters of inheritance and selection that appear in a quantitative genetic model for the evolution growth trajectories and other "infinite-dimensional" traits that we recently introduced. Two methods for estimating the additive genetic covariance function are developed, a "full" model that fully fits the data and a "reduced" model that generates a smoothed estimate consistent with the sampling errors in the data. By decomposing the covariance function into its eigenvalues and eigenfunctions, it is possible to identify potential evolutionary changes in the population's mean growth trajectory for which there is (and those for which there is not) genetic variation. Algorithms for estimating these quantities, their confidence intervals, and for testing hypotheses about them are developed. These techniques are illustrated by an analysis of early growth in mice. Compatible methods for estimating the selection gradient function acting on growth trajectories in natural or domesticated populations are presented. We show how the estimates for the additive genetic covariance function and the selection gradient function can be used to predict the evolutionary change in a population's mean growth trajectory. PMID- 2323561 TI - Are mitochondrial DNA variants selectively non-neutral? PMID- 2323562 TI - Can mating preferences explain changes in mtDNA haplotype frequencies? PMID- 2323563 TI - Variation within and between nucleolar organizer regions in Australian hylid frogs (Anura) shown by 18S + 28S in-situ hybridization. AB - Five distinct classes of secondary constriction are found in the hylid frogs from the genera Litoria and Cyclorana, each of which is defined by its C-banding pattern and morphology (King, 1980, 1987). In-situ hybridization experiments utilizing 18S + 28S copy RNA probes derived from Xenopus and Drosophila rDNA templates, were made on nine species of frogs possessing the major constriction types. Types 1, 2, 4, and 5 are confirmed as being NORs. These results also indicate that type 1 and 2 constriction types are not differentially despiralized as previously suggested, but show absolute differences in the quantity of ribosomal DNA present. This variation took two forms, deletion polymorphism and amplification polymorphism. These differences were observed between homologues within cells and between cells within individuals. Animals possessing these 'despiralized' constrictions are therefore mosaics for both deletion and amplification polymorphisms. Polymorphism frequencies vary greatly between constriction types. Some specimens have a higher level of presence/absence heterozygosity, (L. moorei, type 2, L. nannotis type 5, L. raniformis (animal A, pair 8 type 2), than do others (L. peronii, L. rothii, L. caerulea). The above species also vary markedly in the degree and frequency of amplification of the NORs. The type 4 constrictions analysed (L. coplandi, L. lesueuri and C. novaehollandiae) have a particularly low frequency of presence/absence heterozygosity, and they have fewer size heteromorphisms between homologues. The type 3 ephemeral constrictions did not hybridize to cRNA probes at any stage. In all but one of the species studied, a single pair of chromosomes possessed an NOR. However, in L. raniformis these occurred on two pairs of chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323564 TI - Genetic changes in mating activity in laboratory strains of Drosophila subobscura. AB - Eleven populations of Drosophila subobscura that had been maintained in laboratory conditions during different periods of time were examined for evidence of genetic divergence in mating activity. The results indicate that mating activity increases with the time of maintenance under laboratory conditions. PMID- 2323565 TI - Sequence of DNA replication in Macaca fuscata chromosomes: an outgroup for phylogenetic comparison between man and apes. AB - The relative replication times of every band in the standardized 300 band G-band idiogram of the chromosomes of the Japanese macaque are presented, and compared to the human sequence. Many chromosomes thought to be homologous between Macaca fuscata and man on the basis of standard chromosome banding and gene mapping show a conservation of the replication sequence. Other supposed chromosomal homologies between these two species show no good correspondence, and the replication sequence data suggest that these chromosomes have been subject to complex rearrangements. The replication sequence data also point to possible additional chromosomal homologies between man and M. fuscata. Asynchrony in replication time between homologues from the same cell may also be evolutionarily conserved, because these species share a number of asynchronous homologous bands. Replication band sequence data can provide significant information for comparative cytogenetics. However, usually only the full replication R- or G-band pattern has been used for interspecific comparisons. The dynamic sequence data presented here determine the replication time of every band in the karyotype, and provide a quantitatively and qualitatively more sensitive tool to characterize chromosomes. Such data could provide valuable new information on which to make phylogenetic reconstructions, and shed light on the relationship between chromosome change and evolutionary process. Finally, the M. fuscata replication sequence presented here will provide a necessary foundation for future comparisons between apes and man. PMID- 2323566 TI - Chromosomal analysis and phylogenetic relationships in the Drosophila nasuta subgroup. I. Phylogenetic relationships within the Drosophila sulfurigaster species complex. AB - Phylogenetic relationships within the Drosophila sulfurigaster species-complex, which belongs to the D. nasuta subgroup, were investigated on the basis of chromosomal constitution and morphology. D. pulaua is thought to be the most ancestral species, from which D. s. sulfurigaster and D. s. bilimbata derived in one branch and D. s. albostrigata and D. s. neonasuta in another branch. PMID- 2323567 TI - The inheritance of the piebald spotting pattern and its variation in Holstein Friesian cattle and in Landseer-Newfoundland dogs. AB - The black and white spotting patterns of Landseer dogs are divided into qualitatively recognizable phenotypic classes. Breeding data were obtained from the Swiss Dog Stud Book (SHSB) and from breeders' recent records. A plausible interpretation assumed qualitative inheritance of the generally accepted piebald spotting gene sp1 with at least two modifiers, s2 and s3. The modifier genes are regarded as minor spotting genes and may be responsible for white markings in the related Newfoundland breed which has been cross-bred with Landseers. The proposed scheme of polygenic inheritance can also be applied to the piebald spotting pattern of Holstein-Friesian cattle, using breeding data from literature. PMID- 2323568 TI - Synthesis of an attached autosome, C(3)RM, in Drosophila pseudoobscura. AB - Drosophila pseudoobscura has three acrocentric autosomes. In the experiments reported, homologous arms of the third chromosome were attached to the same centromere. This is a 'reversed metacentric compound' third chromosome, denoted by C(3)RM. This compound chromosome is relatively fertile in within-strain crosses (ca. 50% egg hatch) but sterile when outcrossed to a normal karyotype. When constructing translocations for this experiment, the behavior of the Y autosome translocations suggested that this species can tolerate more Y chromosome deficiency while retaining fertility than can Drosophila melanogaster. Finally, there were no Robertsonian exchanges observed among the 96 autosome autosome translocations analyzed cytologically. PMID- 2323569 TI - Cytogenetic studies on wild house mice from Belgium. AB - The present status of Robertsonian karyotype variation in populations of wild mice from Belgium is presented. Two fusions, Rb(4.12)1Nam and Rb(5.10)3Nam, were identified in the central plain of this flat country. Surrounding this region only mice with the usual 2n = 40 karyotype occurred. From the distribution pattern some possible relationships to other Rb populations from Europe are discussed. PMID- 2323570 TI - Characterization of two divergent beta-tubulin genes from Colletotrichum graminicola. AB - We have cloned and sequenced two beta-tubulin genes, TUB1 and TUB2, from the phytopathogenic fungus, Colletotrichum graminicola. The nucleotide sequences of the coding regions of the two genes are only 72.8% homologous. This divergence is reflected in the deduced amino acid (aa) sequences which differ at 94 aa residues. Comparison with the aa sequences of other fungal beta-tubulins indicates that the C. graminicola TUB2 gene encodes a conserved isotype, whereas the C. graminicola TUB1 product is highly divergent. Both genes contain six identically placed introns and the position of each intron is conserved in other fungal beta-tubulin genes. Also typical of other fungal beta-tubulin genes, there is a pronounced bias in codon usage in the C. graminicola TUB2 gene; there is a lesser codon bias in TUB1 from C. graminicola. Both C. graminicola beta-tubulin genes are transcribed and yield similar sized messages. PMID- 2323571 TI - Cloning and characterization of the highly polymorphic Ser2 gene of Bombyx mori. AB - Three alleles of the sericin (Ser) 2-encoding gene (Ser2), called L, C and mC, were isolated from a Bombyx mori genomic library, and two related ones, called mCL and Cv, were also characterized in B. mori European strains. The Ser2 gene gives rise to two middle silk gland mRNAs by differential splicing. The size of a short mRNA (3.1 kb) is constant, but the length of a longer one ranges from 5 to 6.4 kb depending on the Ser2 allele. These length variations probably result from unequal recombinations in a region which contains about 30 well conserved 45-bp repeats coding for a Ser-like peptide. Furthermore, the L allele (and probably the mCL one) contains a 4.4-kb retrotransposon, resembling the copia-like ones of Drosophila. PMID- 2323572 TI - Nucleotide sequence of rat S-adenosylmethionine decarboxylase cDNA. Comparison with an intronless rat pseudogene. AB - Due to two different polyadenylation signals, two forms of S-adenosylmethionine decarboxylase (AdoMetDC) mRNA (2.1 and 3.4 kb) are present in human and rodent tissues. The nucleotide sequences of rat and human cDNAs corresponding to the shorter mRNA were published previously by us [Pajunen et al., J. Biol. Chem. 263 (1988) 17040-17049]. These sequences covered the coding regions but were incomplete at their 5' ends. Here we report the sequence of rat cDNA spanning the entire longer mRNA with a substantially extended leader region, and compare the sequence with that of a rat psi AdoMetDC pseudogene isolated from a rat genomic library. Relative to the mRNA, the pseudogene has multiple base changes as well as insertions, and deletions. Furthermore, it lacks introns, and is flanked by a short direct repeat. These are typical characteristics of a processed retrogene. PMID- 2323573 TI - Alternative splicing of mRNA encoding rat liver cytochrome P450e (P450IIB2). AB - Cytochrome P450e (P450IIB2) is a phenobarbital(PB)-inducible member of the rat liver P450IIB subfamily. Among P450 cDNA clones previously isolated from a cDNA library made from the liver of a single rat were several that contained P450e inserts, including PB13, PB16, and PB22. By nucleotide sequence analysis, the PB16 and PB22 inserts have now been found to contain an additional 24-bp segment not present in the PB13 insert or in previously reported P450e-coding sequences. According to the published P450e genomic sequence, the 24-bp segment is exactly at the junction of the fifth and the sixth exons and its sequence is identical to the first 24 bp of the fifth intron. Translation of this segment would add 8 amino acid residues to the P450e protein. To detect the alternatively spliced P450e mRNA, a synthetic oligodeoxyribonucleotide (oligo) corresponding to 18 of the 24 bp of the intronic sequence found in the PB16 and PB22 inserts was made. This oligo hybridized with a 2.1-kb RNA on Northern blots of liver RNA from PB- or Aroclor 1254-treated rats. Taken together, these results indicate that individual rats can possess both forms of P450e mRNA and that an alternative splicing mechanism is responsible for their formation. PMID- 2323574 TI - Sequence and factor requirements for faithful in vitro transcription of human 7SL DNA. AB - We have analysed the transcription of a functional human 7SL gene by RNA polymerase III (RNAPIII) in S100 extracts in vitro. Accurate and efficient synthesis of 7S L RNA depends on the presence of (i) an upstream sequence and (ii) an internal promoter element located within the first 22 bp of the gene. These findings were substantiated by DNase I footprinting. Mutations of the internal promoter identified the doublet CG [nucleotide (nt) +15/+16] outside the A-box homologue (nt +5 to +14) as being essential for both proper promoter function in the in vitro transcription assay and competition in the template exclusion assay. Fractionation of S100 extracts identified two fractions required in addition to RNAPIII for faithful transcription of the gene. Each of these two fractions gave rise to one of two footprints observed in DNase I protection experiments, indicating that at least two DNA-binding factors are involved. PMID- 2323575 TI - Secretory synthesis of human interleukin-2 by Streptomyces lividans. AB - To study the ability of Streptomyces lividans to produce heterologous proteins by secretion, we directly fused DNA encoding the leader peptide of the alpha-amylase inhibitor, tendamistat, produced by Streptomyces tendae, with DNA encoding the mature part of interleukin-2 (IL-2). Such cloned fusion constructs are translated in S. lividans, in spite of the quite different codon usage. The active Il-2 is secreted into the culture broth, though the amounts are much less than that of the alpha-amylase inhibitor. The presence of IL-2 in the supernatants could be demonstrated both by an activity assay and by immunoblotting. In addition to the secreted form, three different species of Il-2 antibody immunoreactive proteins, with different Mrs, are either present in the cells or attached to the cells. This indicates that inefficient processing and translocation of the precursor is a major reason for the low activities found in the supernatant. PMID- 2323576 TI - Deduced amino acid sequence of mouse blood-coagulation factor IX. AB - A mouse fetal liver cDNA library was screened with a cDNA clone encoding human blood coagulation factor IX protein (hBCFIX). A bacteriophage lambda clone was isolated and the nucleotide sequence of a 2710-bp insert was determined. An open reading frame of 459 amino acids (aa) was identified within the sequence that has an 80% sequence similarity with hBCFIX. The cDNA contains a long 3'-untranslated sequence similar to that of BcfIX gene from human and canine sources. However, instead of a sequence that might form two hair-pins such as those found in hBcfIX, a (GA)16 repeat that has been reported to form H-DNA [Htun and Dahlberg, Science 241 (1988) 1791-1796; Johnston, Science 241 (1988) 1800-1804] was found in the 3'-untranslated region. The predicted aa sequence of mouse BCFIX serves as a comparative sequence for identifying key residues within hBCFIX where epitopes recognized by monoclonal antibodies produced from an immunized mouse are compared with respect to the human and mouse primary BCFIX sequence. PMID- 2323577 TI - Cloning and sequence analysis of the human gene encoding eosinophil major basic protein. AB - Eosinophil granule major basic protein (MBP), a potent toxin for helminths and mammalian cells, is a single polypeptide rich in arginine. The gene, mbp, was cloned and its nucleotide sequence determined. The 3.3-kb gene consists of six exons and five introns, one of which contains an Alu family repeat. The combined exon sequence is similar to previously reported mbp cDNA sequences. The gene is immediately preceded by a putative promoter containing typical TATA and CCAAT boxes. Southern blots indicate that mbp exhibits limited polymorphism. PMID- 2323578 TI - Cloning and cDNA sequence of the beta-subunit component of human pyruvate dehydrogenase complex. AB - Two cDNA clones (lambda E1 beta 1, 1469 bp; lambda E1 beta 12, 1437 bp) encoding the beta-subunit of the pyruvate dehydrogenase (E1) component of the human pyruvate dehydrogenase complex were isolated from a human liver lambda gt11 cDNA library. The composite human liver E1 beta cDNA encoded the entire mature E1 beta [329 amino acids (aa)] as well as a portion (26 aa) of the E1 beta leader peptide. Significant discrepancies were identified between the nucleotide and deduced aa sequences of human liver E1 beta cDNAs and the corresponding sequences of a previously reported cultured human foreskin fibroblast E1 beta cDNA [Koike et al., Proc. Natl. Acad. Sci. USA 85 (1988) 41-45]. The composite human liver E1 beta cDNA generated in this study provides a reference sequence for investigating the structure-function relationship of human E1 beta and for characterizing genetic mutations in patients with E1 deficiency. PMID- 2323579 TI - Isolation of a human vimentin cDNA with a long 3'-noncoding region from a human osteosarcoma cell line (MG-63). AB - Human vimentin cDNA clones were isolated and sequenced from a lambda gt11 library of the human osteosarcoma cell line MG-63. The 3'-noncoding region of the sequence is 325 nucleotides (nt) long. This cDNA sequence includes both the further 104 nt and the polyadenylation signal site at the 3' end which were earlier predicted from the genomic nt sequence, but had not been found in any previously cloned cDNAs. PMID- 2323580 TI - Dual effects of superoxide dismutase on the autoxidation of 1,4 naphthohydroquinone. AB - The autoxidation of 1,4-naphthohydroquinone, in a phosphate, EDTA buffer at pH 7.4, exhibits an autocatalysis whose lag phase becomes more pronounced in the presence of either the Cu,Zn- or the Mn-containing superoxide dismutases. In contrast, the autoxidation of a second aliquot of the hydroquinone, added after complete oxidation of the first, is linear and is accelerated by superoxide dismutase. Catalase or inactive superoxide dismutase were without effect in either situation. These results are explicable in terms of a free radical chain reaction which is initially propagated by O2- and then, as the quinone accumulates, by univalent reduction of the quinone by the hydroquinone. Reduction of the quinone by O2- diminishes the overall rate of oxidation. It is not necessary to postulate catalysis by superoxide dismutase of the reduction of the semiquinone by O2-. PMID- 2323581 TI - Prevention by free radical scavenger AD5 of prooxidant effects of choline deficiency. AB - This study was designed to explore the possible preventive effects of a novel radicophile, N-p-methoxyphenylacetyl-dehydroalanine (AD5) and three other antioxidants, N,N'-diphenyl-p-phenylenediamine (DPPD), butylated hydroxyanisole (BHA) and a water-soluble analogue of vitamin E, trolox C, on the acute effects of the liver of feeding a choline-deficient (CD) diet. It has been suggested that some of the acute effects of a CD diet are related to free radicals, the generation or metabolism of which is disturbed in this acute dietary model. AD5 was found to be very effective in preventing nuclear lipid peroxidation, DNA damage and cell death induced by a CD diet but to have little effect on triglyceride accumulation ("fatty liver"). DPPD, BHA, and trolox C were ineffective. These results add strength to the hypothesis that oxygen free radicals might be an important component in the early events during carcinogenesis induced by feeding a CD diet. PMID- 2323582 TI - The effect of zinc on reperfusion arrhythmias in the isolated perfused rat heart. AB - Considerable evidence suggests that free radicals engendered by redox-active metals, particularly iron and copper, are causative agents in reperfusion injury following ischemia. This study demonstrates that perfusion of the isolated rat heart with a buffer containing zinc, a non-redox active metal similar to copper in its coordination chemistry, inhibits the development of ventricular arrhythmias during reperfusion. Zinc was employed as the bishistidine complex, Zn -His2, to maintain solubility and permeability. Zn--His2 exerted an antiarrhythmic activity as hearts spent a longer time in normal sinus rhythm and a shorter time in ventricular fibrillation during reperfusion following 10 min of regional ischemia. However, Zn--His2 also produced a negative inotropic and chronotropic effect, evident during equilibration and ischemia. In the course of experiments which began in Israel and continued in the U.S. it was necessary to use two different sources of rats. Hearts from the two sources manifested different sensitivities to the concentrations of Zn--His2, although their physiological effects were similar. Differential activity responses were noted for antiarrhythmic activity, negative inotropic and chronotropic properties, and toxicity. In both groups of untreated hearts the incidence of ventricular fibrillation after ischemia was 100%. Ventricular fibrillation was reduced to 17% at 37.5 microM Zn--His2 in the U.S.-bred rat hearts and to 9% at 200 microM Zn- His2 in those from Israel. These changes in Zn--His2 treated animals were accompanied by a decrease in lactate dehydrogenase release from the myocardium during reperfusion. None of the protective effects was due to histidine alone. These results indicate that zinc prevents ventricular arrhythmias during reperfusion following regional ischemia and may prevent membrane damage, possibly, by reduction of free radical formation. PMID- 2323583 TI - Iron status in the acute phase and six weeks after myocardial infarction. AB - In a case-control study of 84 myocardial infarction patients and 84 population controls we investigated the association between iron status parameters and myocardial infarction during the acute phase and after six weeks. Immediately after the infarction mean ferritin levels were significantly higher, whereas iron levels and iron saturation of transferrin were significantly lower in cases than in controls. Six weeks after the infarction, serum iron levels were still significantly lower in cases than in controls. Neither serum ferritin levels nor serum iron levels did show a clear association with the size of the ischemic tissue damage as estimated by creatine phosphokinase levels. Our results indicate that serum ferritin and iron levels are influenced by the traumatic effects of the myocardial infarction. Possibly, these transient changes are an acute effect, as seen in infections. An increased uptake of iron in the reticulo-endothelial system for synthesis of ferritin, may account for the lowered serum iron level and the iron saturation of transferrin. PMID- 2323584 TI - Spin-trappers and vitamin E prolong endurance to muscle fatigue in mice. AB - The involvement of free radicals in endurance to muscle effort is suggested by experimental and clinical data. Therefore, experiments have been performed to observe the effect of trapping free radicals on endurance to swimming in mice. Animals were injected intraperitoneally with each of three spin-trappers [N-tert Butyl-alpha-Phenyl-Nitrone (PBN),alpha-4-Pyridyil-1-Oxide-N-tert-Butyl-Nitrone (POBN) and 5,5-Dimethyl-1-Pirrolyn-N-Oxide (DMPO): 0.2 ml of 10(-1) molar solution]. Each mouse was submitted to a swimming test to control resistance to exhaustion a) without any treatment, b) after administration of each spin-trapper in a random order c) after saline. Control experiments were performed with saline and with vitamin E. Endurance to swimming was greatly prolonged by pretreatment with all the spin-trappers (DMPO less than 0.0001; POBN less than 0.0001; PBN less than 0.001) and with Vitamin E. Experiments state that compared to treatment with spin-trappers or Vitamin E, administration of saline alone did not enhance time to exhaustion so that the increase in time to exhaustion with the various free radical scavengers was not the effect of training. Therefore, free radicals could be considered as one of the factors terminating muscle effort in mice. PMID- 2323585 TI - Oesophageal and gastric motor activity in patients with bulimia nervosa. AB - Previous studies showed that symptoms of oesophageal motor disorders can be misinterpreted as indicating anorexia nervosa and that in primary anorexia nervosa gastric motility is frequently impaired. We investigated in 32 women with bulimia nervosa whether symptoms of oesophageal motor disorders could be obscured by or be mistaken as forming part of bulimic behaviour, and whether impaired gastric motility was frequent as well. Oesophageal motility was normal in 18 of 26 patients studied, another four had incomplete lower oesophageal sphincter relaxation. Two patients had vigorous achalasia and each one achalasia and diffuse oesophageal spasm, all of whom experienced two types of vomiting: one self-induced and one involuntary, in which the vomit was non-acidic and tasted as the preceding meal. Gastric emptying of a semisolid meal was studied in all patients except of the eight with oesophageal motor abnormalities. Emptying was significantly slower than in healthy controls and grossly delayed in nine of 24 patients. Antral contraction amplitudes were lower and increased less postcibally than in controls. In conclusion (i) bulimic behaviour can obscure symptoms of oesophageal motor disorders and (ii) gastric emptying is frequently delayed in bulimia nervosa. PMID- 2323586 TI - Oesophageal acidification does not increase lower oesophageal sphincter pressure. AB - We studied the effect of distal oesophageal acidification on lower oesophageal sphincter (LOS) pressure in normal human volunteers and in cats. The distal oesophagus was acidified by intraluminal injection of 0.1N HCl (pH 1.2). The LOS pressure was recorded by a sleeve device while pharyngeal and oesophageal pressures were monitored by nonperfused, water filled catheters. In normal human subjects, distal oesophageal acidification did not elicit a change in LOS pressure. In anaesthetised cats, injection of acid into the distal oesophagus elicited immediate LOS relaxation followed by a secondary peristaltic sequence. With propagation of the peristaltic sequence into the LOS, the LOS pressure abruptly increased 20-100 mmHg and gradually returned to the preinjection value over 15-180 s. In the one instance in which we were able to acidify the distal oesophagus without evoking secondary peristalsis, the LOS pressure did not change. Injection of saline into the distal oesophagus evoked a response in the LOS and oesophageal body that was indistinguishable from that seen with acid. We conclude that contrary to common belief, distal oesophageal acidification itself does not affect LOS pressure in man or the cat. PMID- 2323587 TI - Arterial oxygen saturation during upper gastrointestinal endoscopy: the effects of a midazolam/pethidine combination. AB - This study was performed to assess the severity and duration of hypoxia during and after prolonged upper gastrointestinal endoscopy. Twenty patients were studied using a non-invasive pulse oximeter. Significant reductions in oxygen saturation were noted during endoscopy and remained below the preexamination level during the one hour period after the examination. This study indicates that pulse oximetry is a useful monitor for detection of hypoxia during and after endoscopy. PMID- 2323588 TI - Serum gastrin concentration affects the self replication rate of the enterochromaffin like cells in the rat stomach. AB - The influence of antrectomy and antrum exclusion on the enterochromaffin like cell kinetics in the gastric mucosa of the rat was studied using a combination of histamine immunocytochemistry and autoradiography after in vivo labelling with tritiated thymidine. In all experimental groups, the enterochromaffin like cells were found to incorporate the DNA precursor, thus indicating an ability to divide. The serum gastrin concentration was raised by antrum exclusion and reduced by antrectomy. After antrum exclusion, the enterochromaffin like cell proliferation rate increased as indicated by a doubling of the labelling index and by the resulting enterochromaffin like cell hyperplasia (after six weeks). After antrectomy, the enterochromaffin like cell labelling index decreased to reach 25% of the control value; at this time the enterochromaffin like cell density had not decreased significantly. The observed correlation between the enterochromaffin like cell labelling indices and the serum gastrin concentration supports the hypothesis that enterochromaffin like cell proliferation is influenced by serum gastrin. PMID- 2323589 TI - Relationship between gastrin cell number, serum, antral mucosa and luminal gastrin concentration and gastric acidity in antral atrophic gastritis. AB - The aim of our study was to investigate the relationship between gastrin producing cell density with antral mucosa, luminal and serum gastrin concentration in antral atrophic gastritis. Our study group consisted of 17 patients: six with mild atrophic gastritis, seven with moderate atrophic gastritis and four with severe atrophic gastritis. None of the patients had type A atrophic gastritis but the body mucosa was affected by superficial gastritis at various extent in some. A group of 15 healthy subjects served as control. All subjects underwent gastroscopic examination with multiple bioptic sampling. Radioimmunoassay was used for gastrin determination and photomicroscopy for gastrin producing cell density assessment. Electron microscopy was used to assess the gastrin producing granule density index. Patients with moderate and severe atrophic gastritis showed a lower gastric acidity and acid output as compared to control. Serum gastrin did not show significant differences among the groups. In moderate and severe atrophic gastritis, gastrin producing cell granule density index, gastrin producing cell density and antral mucosa gastrin concentration were significantly lower when compared with control and decreased with advancing of the severity of atrophic gastritis. In atrophic gastritis, however, the latter two measurements were not correlated. In moderate and severe atrophic gastritis luminal gastrin concentration significantly increased, compared with control, after the severity of atrophic gastritis. Gastrin producing cell granule density index and luminal gastrin concentration showed a significant correlation with gastric pH. These data suggest that in antral atrophic gastritis with reduced gastric acidity, the decrement of gastrin producing cells is followed by gastrin producing cell hyperfunction with increased luminal release of gastrin. PMID- 2323590 TI - Lymphocytic gastritis--prospective study of its relationship with varioliform gastritis. AB - Lymphocytic gastritis is a new histopathological entity characterised by a dense lymphocytic infiltration of surface and pit gastric epithelium. Previous retrospective work has suggested that lymphocytic gastritis is related to an endoscopic form of gastropathy comprising enlarged folds, nodules and erosions, commonly denoted as varioliform gastritis. In the present prospective study, the relationship is clearly shown; nearly 82% (54/66) of the varioliform gastritis observed in four different endoscopy units correspond histologically to lymphocytic gastritis. The correlation is even better if cases showing strictly antral localisation are excluded (53/55) - that is, more than 96%. The histological concept of lymphocytic gastritis seems, however, to extend beyond varioliform gastritis as of 67 cases of lymphocytic gastritis diagnosed during the period under study, one third had no particular endoscopic expression. PMID- 2323591 TI - Longterm oral cisapride improves interdigestive antroduodenal motility in dyspeptic patients. AB - We have evaluated the effect of cisapride on interdigestive antroduodenal motility during a prolonged oral therapy in 20 consecutive dyspeptic subjects. Individuals with less than two migrating motor complexes (MMCs) starting from the antral region in 240 minutes and without evidence of upper gastrointestinal tract diseases were randomly treated with either cisapride (10 cases), or placebo (10 cases) for 15 days. Computerised manometry of antroduodenal region was performed for 240 minutes, in basal conditions and on the 15th day of therapy. Symptomatic evaluation of patients was also performed before and after treatment. After cisapride administration, a significant increase in the incidence of antral migrating motor complexes was noticed (p = 0.022); likewise, the motility index, calculated for phase-2 periods, appeared to be significantly higher both in the antrum and in the duodenum (p less than 0.001). Symptomatic improvement was observed in both groups, with a hardly significant (p = 0.049) reduction of dyspeptic symptoms severity only but not of frequency in cisapride treated patients v controls. We conclude that longterm oral therapy with cisapride improves interdigestive antroduodenal motor activity. PMID- 2323592 TI - Characterisation of the effector cells responsible for the in vitro cytotoxicity of blood leucocytes from aphthous ulcer patients for oral epithelial cells. AB - This study was designed to identify the cells responsible for the spontaneous cell mediated cytotoxic effect (SCMC) exerted by peripheral blood leucocytes from patients with recurrent aphthous ulceration, towards cultured oral epithelial cells. Peripheral blood leucocytes from recurrent aphthous ulceration patients exerted a significantly greater (p less than 0.01) degree of cytotoxicity towards the oral epithelial target cells than did peripheral blood leucocytes from healthy control subjects, or from patients with non-specific ulceration. Depletion of CD-5 positive cells (T-lymphocytes) resulted in a significant decrease in the SCMC in aphthous patients. Depletion of CD-16 positive cells (NK cells) produced no significant change in cytotoxicity. T-lymphocytes, therefore, appear to be intimately involved in the in vitro SCMC effect in recurrent aphthous ulceration. PMID- 2323593 TI - Breath hydrogen response to lactulose in healthy subjects: relationship to methane producing status. AB - In order to assess the relationship between methane (CH4) producing status and the breath excretion of hydrogen (H2) in healthy subjects, breath CH4 and H2 were simultaneously measured for 14 hours after oral ingestion of 10 g lactulose in 65 young volunteers. Forty were breath CH4 producers and 25 were not. Statistically significant differences were observed between both groups, with lower values for CH4 producers recorded for the following parameters: fasting basal value of breath H2 (8.1 (4.9) v 5.2 (3.7) ppm, p less than 0.05), mouth-to-caecum transit time (68 (24) v 111 (52) min, p less than 0.005), and breath H2 production measured as area under the curve 13.1 (6.9) v 8.8 (3.8) 10(3) ppm/min, p less than 0.02). There was no significant correlation between individual production of breath H2 and CH4. These results indicate that the response to lactulose depends on breath CH4 producing status. In clinical practice, defining normal values of mouth-to-caecum transit time without knowledge of breath CH4 producing status may lead to misinterpretation of the H2 breath test. PMID- 2323594 TI - Protein synthesis of muscle fractions from the small intestine in alcohol fed rats. AB - The effects of chronic ethanol feeding on the amounts and synthesis rates of cytoplasmic, contractile, and stromal protein fractions were investigated in the small intestine of eight pairs of immature and seven pairs of mature rats. Treated rats were fed ethanol as 36% of total energy in a nutritionally adequate liquid diet. Paired controls were fed isovolumetric amounts of the same diet in which ethanol was substituted by isocaloric glucose. After six weeks the total cytoplasmic and contractile protein content in immature rats was reduced by 18% and 31%, respectively (p less than or equal to 0.007). The decline in the stromal protein content (26%) was not statistically significant (p = 0.130). In mature rats the protein contents were also reduced in the cytoplasmic (25%, p = 0.035) and contractile (27%, p = 0.005) protein fractions, though the stromal protein fraction was unaltered (p = 0.913). In immature rats fractional rates of protein synthesis in cytoplasmic and contractile protein fractions of the small intestine were unaltered by chronic ethanol feeding (p less than or equal to 0.853). In mature rats, the synthesis rates of corresponding fractions declined, by 18% and 31%, respectively, but were also not statistically significant (p less than or equal to 0.369). Absolute rates of protein synthesis in immature rats fell by 6% (p = 0.549) in the cytoplasmic and 31% in the contractile protein fraction (p = 0.045). In mature rats, the corresponding reductions were 38% (p = 0.106) and 48% (p = 0.033), respectively. Virtually no radioactivity could be detected in the stromal fraction, signifying very low synthesis rates. Chronic ethanol feeding reduces the amount of protein in the small intestine of the immature and mature rat with the contractile protein fraction showing the greatest decrease. In the absence of statistically significant reductions in fractional synthesis rates a partial adaptation in turnover rates may have occurred. PMID- 2323595 TI - Systemic factors are trophic in bypassed rat small intestine in the absence of luminal contents. AB - Mucosal histology, crypt cell proliferation and brush border enzymes were measured in rats with varying degrees of jejunoileal bypass, in order to compare the effect of systemic and luminal factors on adaptive growth and differentiation (brush border enzymes) in small intestinal epithelium. Eighty five percent jejunoileal bypass caused a functional short gut; in intestine remaining in continuity there were significant increases in segmental weight, villus area and crypt depth, compared with sham operated controls and 25% jejunoileal bypass rats. Despite villus cell hyperplasia in 85% bypass rats, mucosal sucrase and alkaline phosphatase fell in jejunum and remained low in ileum, while leucine amino peptidase rose in ileum. There was a significant fall in villus area (p less than 0.01) and crypt cell production (p less than 0.001) in self emptying loops of 25% bypass rats not exposed to luminal contents compared with control segments of sham operated rats. In contrast, self emptying loops of 85% bypass rats were not atrophied despite the much greater distance from luminal nutrients; the villus area (p less than 0.01) and crypt cell production (p less than 0.005) were higher than in 25% bypass rats, and at least as great as in sham operated rats. These results indicate that adaptive hyperplasia has a variable effect on expression of brush border enzymes which might reflect villus cell immaturity. The atrophic effect of diversion of luminal contents can be counteracted by systemic growth factors released as part of the adaptive response; thus systemic growth factors are not dependent on a permissive effect of luminal contents. PMID- 2323596 TI - Quantitative histological study of enteropathy associated with HIV infection. AB - A quantitative histological study was performed on small intestinal biopsies from eight ambulatory patients with HIV infection (AIDS/AIDS-related complex, ARC) and compared with those from 16 normal subjects. Enteropathy was assessed by measurement of villus area, crypt length and mitotic count, as well as duodenal counts of intraepithelial lymphocytes, mucosal mast cells and goblet cells. Enteropathy in subjects with AIDS/ARC was shown by reduced mean villus area of 0.363 (SD 0.081) compared with 0.500 (SD 0.064) mm2 in control subjects (p less than 0.0001), while intestinal crypts were of similar length with 239 (SD 36) compared with 225 (SD 28 microns, but mitotic count was increased to 3.8 (SD 1.2) compared with 2.4 (SD 0.8) (p = 0.01) in the same control subjects. These results indicate villous atrophy with impaired crypt hyperplasia. Duodenal cell counts showed similar numbers of mucosal mast cells, intraepithelial lymphocytes and goblet cells in AIDS/ARC patients and fifteen control subjects. PMID- 2323597 TI - Goblet cell carcinoid of the appendix. AB - We have reviewed all cases of goblet cell carcinoid in the Department of Pathology, Edinburgh University. Of the 10 cases identified, two had died as a result of the tumour. This would suggest a poorer prognosis than is generally recognized. Those patients who subsequently had progression of their disease were not predicted by histological criteria. Because of the unpredictable behaviour of these tumours we recommend that such patients should correctly be treated by a right hemicolectomy. PMID- 2323598 TI - Glucocorticoid treatment in ileal Crohn's disease: relief of symptoms but not of endoscopically viewed inflammation. AB - The effect of prednisolone (20-30 mg daily for six to nine weeks) was studied in eight patients with Crohn's disease and recurrent, preanastomotic ileal inflammation, in respect of symptoms, endoscopic findings and phospholipase A2 activity in the ileal mucosa. The Harvey-Bradshaw Crohn's disease activity index improved significantly, mainly because of reduced frequency of loose stools and diminution of abdominal pain. Endoscopy revealed no corresponding decrease in ileal inflammation, which in all cases persisted after treatment. The phospholipase A2 activity in the ileal mucosa was not altered by prednisolone. In two of three patients with concomitant colitis colonic inflammation improved. The study confirmed earlier reports of good symptomatic relief from glucocorticoid treatment in Crohn's disease of the small bowel, but endoscopy suggests that this improvement was not the result of resolution of small intestinal mucosal inflammation. PMID- 2323599 TI - Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study. AB - Factors affecting colectomy rate were studied in a retrospective population based series of 1586 patients with ulcerative colitis, in Stockholm County during 1955 84. Five hundred and sixty eight patients (36%) had total colitis at diagnosis, 603 patients (38%) left sided colitis, and 397 patients (25%) proctitis. During a median period of observation of 13 years 514 patients were treated by colectomy. The five, 10, and 25 year cumulative colectomy rate were 20% (CI 18-22%), 28% (CI 26-30%), and 45% (CI 41-49%) respectively. The main factor affecting the colectomy rate was the extent of disease at diagnosis. Patients with total colitis showed a five, 10, and 25 year cumulative colectomy rate of 32% (CI 28 36%), 42% (CI 38-46%), and 65% (CI 58-72%) respectively. Ten per cent of the 1586 patients had a colectomy during the first year after diagnosis, 4% during the second year and 1% during subsequent years. The age at diagnosis and sex did not affect the cumulative colectomy rate. Elective colectomy was performed in 322 cases (63%) and acute colectomy in 192. The duration of disease before colectomy fell during the study period due to a more standardised criteria for colectomy in severe attacks. One hundred and twenty nine (66%) of the acute colectomies were performed within two years from diagnosis. PMID- 2323600 TI - Fine needle aspiration cytology of rectal masses. AB - This paper describes the results of transproctoscopic fine needle aspiration cytology in the diagnosis of rectal lesions. Fifty one consecutive patients referred with a presumptive diagnosis of rectal mass were subjected to proctoscopic examination when fine needle aspiration cytology, brush cytology and biopsy samples were taken. Of the 30 patients of malignancy of rectum in whom all the three sampling techniques were applied, the biopsy was positive in 27 (90%), brush cytology in 25 (83.3%) and fine needle aspiration cytology in 29 (96.6%). A combination of fine needle aspiration cytology with brush cytology gave a positive yield in 96.6% while that fine needle aspiration cytology with brush cytology gave a yield of 100%. Fine needle aspiration cytology was most helpful in infiltrative tumours. All 10 patients with secondaries in the pouch of Douglas or rectovesical pouch, and the single patient with submucosal rectal carcinoma were correctly diagnosed at fine needle aspiration cytology. There were no false positive results with fine needle aspiration cytology and no complications were encountered with the procedure. PMID- 2323601 TI - Recovery of menstruation and pregnancy after liver transplantation. AB - The effect of successful liver transplantation on menstrual function was assessed by questionnaire in 44 women transplanted for various types of end stage liver disease, acute liver failure or malignant disease. Significant amenorrhoea (greater than one year) was present in 48% of women with chronic liver disease before transplantation, and was reversed within 10 months of surgery in all but one of the premenopausal patients who had primary amenorrhoea and hypogonadotrophic hypogonadism. Two patients became pregnant five months and 1.5 years after transplantation, but in one instance the pregnancy was unsuccessful, possibly as a consequence of cyclosporin related intrauterine growth retardation. PMID- 2323602 TI - Portal hypertension in chronic hepatitis: relationship to morphological changes. AB - Various anatomical factors were examined which might provide passive resistance to portal venous flow and so cause portal hypertension. Methods included the measurement of portal pressure (WHVPG) in cirrhotic and non-cirrhotic patients, morphological assessment by semiquantitative grading of severity of disease, calculation of hepatocyte size indices, and assessment of volume density of hepatocytes, sinusoids, Disse's space and Disse's space collagen by electron microscopy. The wedged hepatic venous pressure gradient increased with progression of disease and portal hypertension was present before histologically detectable cirrhosis had developed. With increasing progression of disease towards cirrhosis, the relationship between individual and aggregated features and the WHVPG diminished and lost statistical significance. Hepatocyte size increased with progression of histological changes and correlated significantly with increase of WHVPG, both in non-alcoholic and alcoholic patients. Disse's space collagen was increased significantly in non-alcoholic chronic active hepatitis compared with patients with near-normal liver. No significant decrease of sinusoidal space was found. Multiple factors rather than any single feature influence the development of portal hypertension. PMID- 2323603 TI - Bismuth induced encephalopathy caused by tri potassium dicitrato bismuthate in a patient with chronic renal failure. AB - A 68 year old man with a creatinine clearance rate of only 15 ml/min took twice the recommended dose of tripotassium dicitrato bismuthate (TDB) as DeNol liquid; 10 ml qds; a total of 864 mg bismuth daily for two months. Whole blood bismuth concentrations rose to 880 micrograms/l and he developed global cerebral dysfunction with hallucinations, ataxia, and an abnormal EEG. Renal clearance of bismuth rose from 0.24 to 2.4 ml/min when the heavy metal chelator 2-3 dimercapto 1 propane sulphonic acid (DMPS) was given by mouth. Bismuth was measured by a novel method involving inductively coupled plasma source mass spectrometry. Fifty days after stopping TDB, whole blood bismuth concentrations fell to 46 micrograms/l and the patient's EEG returned to normal. His mental function also recovered completely. The case serves as a timely reminder that TDB should not be administered to patients with renal disorders, as stated in the data sheet. PMID- 2323604 TI - Influence of time of dinner on nocturnal gastric pH. PMID- 2323605 TI - Study of ovarian tumors treated at Nagoya University Hospital, 1965-1988. AB - The relative frequency and the age distribution of ovarian tumors (873 primary and 47 secondary tumors) encountered over 23 years at Nagoya University Hospital were examined with respect to histological type and grade of malignancy. Of the primary neoplasms, common epithelial tumors accounted for 56.6%, sex cord-stromal tumors for 7.3%, and germ cell tumors for 39.5%. Among 296 cases with primary malignant neoplasms, common epithelial type accounted for 75.6%, sex cord-stromal tumors for 4.7%, and germ cell tumors for 19.6%. A review of the literature from Western countries indicated that in Japan, the relative frequency of common epithelial tumors is lower but that of germ cell tumors, especially malignant germ cell tumors, is higher. The difference in the incidence of germ cell tumors between Japan and Western countries is not considered significant, and the incidence of common epithelial tumors is considered to be much lower in Japan. PMID- 2323606 TI - Virulence of papillary endometrial carcinoma. AB - While uterine papillary serous carcinoma (UPSC) has been well described as a virulent subtype of endometrial adenocarcinoma (AC), with behavior similar to that of papillary serous ovarian carcinoma, the papillary endometrial (PE) variant has not been well characterized. We studied 117 patients with endometrial carcinoma identified by our tumor registry, pathology files, and practice records from March 1981 to February 1989: 76 with AC, 26 with PE, and 15 with UPSC. Age and demographic data were similar for all three groups. All of the AC patients, 84% of PE patients, and 87% of UPSC patients had early-stage disease by clinical exam; however, 10% of AC patients, 23% of PE patients, and 87% of UPSC patients had extrauterine disease at surgery (P less than 0.05). Deep myometrial invasion occurred in 29% of AC patients, 36% of PE patients, and 60% of UPSC patients (P less than 0.05). Comparative analysis of the PE and UPSC groups revealed more marked nuclear anaplasia (P less than 0.05) and more frequent vascular space involvement (nonsignificant) in the UPSC group. At 3 years, 75% of the AC group was alive without disease. In contrast, the median progression-free interval for the PE group was 33 months, and for the UPSC group, 9 months (P less than 0.05). These data suggest a transition of increasing virulence corresponding with increasing papillary features, from AC to PE to UPSC. The papillary feature may be a new, significant risk factor in endometrial carcinoma. PMID- 2323607 TI - Scalene lymph node sampling in cervical carcinoma: a reappraisal. AB - Scalene lymph node sampling to detect occult metastases from cervical carcinoma has been reported to have varying degrees of clinical utility. During the past 7 years at the Los Angeles County University of Southern California Medical Center, 17 scalene lymph node samplings were performed in patients with clinical stage IB to IIIB cervical carcinoma who had metastases to the paraaortic lymph nodes, negative chest X ray, and no clinical evidence of scalene/supraclavicular node metastases. Four of the patients were demonstrated on microscopic examination to have scalene lymph node metastases (23.5%). There were no serious complications related to this surgery. Patients with cervical carcinoma whose only extra pelvic site of metastases is the paraaortic modes should be considered for scalene lymph node sampling as part of their pretreatment evaluation, especially if extended field radiation is contemplated. PMID- 2323608 TI - Primary ovarian malignant amelanotic melanoma arising in cystic teratoma. AB - A case of primary ovarian malignant amelanotic melanoma arising in a cystic teratoma is presented with the histology, immunohistochemistry, and ultrastructure of the tumor. PMID- 2323609 TI - Lack of acute toxicity associated with a multimodality treatment of stage III ovarian epithelial carcinoma. AB - Eleven patients with advanced stage III ovarian epithelial carcinoma were treated primarily according to an aggressive multimodality plan utilizing cytoreductive surgery, chemotherapy (high-dose cisplatin and Cytoxan), and consolidative radiation therapy (abdominopelvic "bath" plus pelvic boost). The treatment was tolerated remarkably well. There was no evidence of progressive disease during treatment, and all patients showed a positive response. There was a notable lack of significant acute morbidity, with the exception of a severe symptomatic peripheral neuropathy associated with cisplatin doses of 200 mg/m2. This was not evident with doses of cisplatin up to 150 mg/m2. PMID- 2323610 TI - Intraperitoneal cytosine arabinoside administered in sequence with systemic cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. AB - After standard management of stage III-IV ovarian cancer patients by surgical reduction of tumor mass and subsequent cisplatin-based combination chemotherapy, eradication of residual intraabdominal disease remains a major clinical problem. In an effort to increase response to therapy without adding marrow toxicity, after laparotomy, 21 stage III-IV ovarian cancer patients were treated with systemic chemotherapy comprising cisplatin, doxorubicin, and cyclophosphamide (PAC) on Day 1 followed by intraperitoneal (ip) cytosine arabinoside (Ara-C) on either Day 8 or 14, every 28 days. Ara-C, an S-phase-specific drug, was administered ip to exploit the pharmacologic advantage of an ip regimen at a time when a possible PAC-induced recruitment of cells into the proliferative pool could further maximize cell kill. Kinetic features of ovarian neoplastic cells recovered from peritoneal washings were monitored during treatment by measurement of the thymidine labeling index (TLI): data from four patients indicate that there is an increase in proliferating cells on Days 8 and 14 after PAC treatment. Toxicity of treatment was acceptable. Although 95% of evaluable patients had more than 2 cm of residual disease, response was observed in 47% of patients. The therapeutic potential of this regimen should be tested in patients with small volume disease after debulking surgery. PMID- 2323611 TI - Predictive value of CA 125 during early chemotherapy of advanced ovarian cancer. AB - CA 125 was measured during early chemotherapy of 61 patients with epithelial ovarian carcinomas (FIGO stages III and IV) to determine if patients with a poor response to further treatment could be identified during early therapy. Blood samples were drawn before the start of chemotherapy and 1 month after the first, second, and third courses. Prior to therapy all patients had increased CA 125 levels, but 77% (47/61) had normal antigen levels after the third course. Second look laparotomy was performed 4-10 months after the third course; 24 patients had no evidence of disease (NED) and 37 had residual tumor (RT). After three courses of chemotherapy, NED patients all had normal CA 125 values, whereas 38% (14/37) of the RT patients had increased antigen levels. In conclusion, increased CA 125 values after the third course of chemotherapy identified 38% of the patients who responded insufficiently to further therapy. Treatment in progress should here be stopped and replaced by palliative therapy if other curative regimens are considered nonexistent. Normal CA 125 values had no predictive value owing to the many (62%) false-negative antigen values. PMID- 2323612 TI - Intraoperative frozen section diagnosis of depth of myometrial invasion in endometrial adenocarcinoma. AB - From January 1981 to December 1988, a prospective trial was conducted on 216 consecutive patients undergoing hysterectomy for FIGO stage I endometrial adenocarcinoma to determine the accuracy of intraoperative frozen section (IFS) diagnosis of depth of myometrial invasion. IFS and D&C diagnoses were compared to the permanent section diagnosis to determine their accuracy. Patients with an IFS or D&C diagnosis of grade 3 carcinoma, deep myometrial invasion, cervical invasion, or adnexal involvement were considered high risk for paraaortic nodal metastasis, and paraaortic lymphadenectomy was performed. IFS correctly diagnosed the depth of myometrial invasion in 194 of 204 cases (95%). The sensitivity of IFS diagnosis of deep invasion was 87%, the specificity was 99%, the positive predictive value was 98%, and the negative predictive value was 94%. Grade, subtype, cervical invasion, and adnexal involvement were also accurately diagnosed. Based on IFS and D&C diagnosis, paraaortic lymphadenectomy was performed in 32% of patients, while 68% were considered low risk and were spared paraaortic lymphadenectomy. Eight patients (5%) were incorrectly diagnosed as low risk and did not have paraaortic lymphadenectomy performed. Sixty-five of seventy three (90%) patients considered high risk on permanent section had paraaortic lymphadenectomies performed on the basis of IFS and D&C diagnosis. Inaccurate IFS diagnosis of depth of myometrial invasion can occur when tumor involves the uterine isthmus or cornua and when tumor invades areas of adenomyosis. PMID- 2323613 TI - Pelvic radiation in stage I endometrial adenocarcinoma with high-risk attributes. AB - From 1977 to 1987, 45 patients with FIGO stage I endometrial adenocarcinoma with high-risk attributes and disease confined to the pelvis were prospectively treated with postoperative pelvic radiation. By study design, all patients underwent staging laparotomy with pelvic and paraaortic lymphadenectomy. All patients had either grade 1 or 2 adenocarcinoma and greater than 50% myometrial invasion or grade 3 adenocarcinoma with less than or greater than 50% myometrial invasion. The estimated 5-year survival for all 45 patients was 77% and the 5 year disease-free interval was 82%. Regional control was achieved in 89% of all patients, with 4% recurring at distant sites. When patients were stratified according to surgical-pathologic findings, 33 patients with disease confined to the uterus or uterus and pelvic nodes (surgical stage I) had estimated 5-year survival and disease-free interval of 88%. Of these 33 patients, 10 with grade 1 or 2 adenocarcinoma and deep myometrial invasion had 5-year disease-free intervals of 100%, while 23 patients with grade 3 adenocarcinoma with less than or greater than 50% myometrial invasion had disease-free intervals of 79 and 91%, respectively. From these results, it was concluded that patients with high-risk attributes demonstrated to have disease confined to the uterus or uterus and pelvic nodes can achieve excellent survival following surgical staging and postoperative pelvic radiation. PMID- 2323614 TI - Evaluation of different surgical approaches in the treatment of endometrial cancer at FIGO stage I. AB - From January 1, 1970 to December 31, 1979, 425 cases of endometrial carcinoma, FIGO stage I, were treated at the First Department of Obstetrics and Gynecology, University of Milan. Three different surgical approaches were used: total abdominal hysterectomy with bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy was performed in 245 women, total abdominal hysterectomy and bilateral salpingo-oophorectomy without pelvic lymphadenectomy in 100, and vaginal hysterectomy with bilateral salpingo-oophorectomy in 80. Five-year survival was evaluated as a function of risk factors (histological grade, depth of myometrial invasion, metastatic nodes) in the three groups of patients, and we conclude that lymphadenectomy is useful for prognostic purposes but does not confer a therapeutic benefit. PMID- 2323615 TI - Management of epithelial ovarian neoplasms using a platinum-based regimen: a 10 year experience. AB - One-hundred and twenty-four patients with primary advanced (n = 103) and recurrent (n = 21) ovarian carcinoma completed a course of platinum-based chemotherapy (cyclophosphamide/doxorubicin/cisplatin or cyclophosphamide/cisplatin) or developed progressive disease while on therapy and were evaluated. All patients were treated between August 1, 1977 and December 31, 1987. The 5-year survival for patients with primary disease was 27% for stage III (n = 73) and 7% for stage IV (n = 30). The 5-year survival based on residual disease was 91% for microscopic disease (n = 13), 24% for disease less than 2 cm (n = 27), and 8% for disease greater than or equal to 2 cm (n = 64). The 5-year survival for the patients treated with recurrent disease was 5% (n = 21). Borderline tumors have been excluded. Long-term toxicity, including cardiac toxicity, renal toxicity, and a 5% incidence of second primary tumors, is evaluated. PMID- 2323616 TI - Optimal therapy for pelvic recurrence after radical hysterectomy for early-stage cervical cancer. AB - Forty-eight patients with pelvic recurrence after radical hysterectomy were evaluated. The influence of location of pelvic recurrence (sidewall versus central), histological grade, histological type, and interval from hysterectomy to recurrence had no influence upon curability by radiotherapy. Ten of twenty eight patients treated by primary radiation therapy for recurrent disease remain without evidence of disease a minimum of 12 months post-therapy, with a projected 5-year disease-free survival in excess of 30%. No patient treated with adjuvant radiation after initial surgery was rendered disease free by subsequent treatment with radiotherapy. Eleven patients were explored for exenterative surgery. Three of six in whom exenteration was technically feasible remain alive without evidence of disease. None of 15 patients treated with chemotherapy remain free of disease. Radiation therapy remains the treatment of choice in post-radical hysterectomy recurrences confined to the pelvis. As exenterative therapy will result in the cure of a small number of patients with disease confined to the pelvis, exenteration should be considered in patients treated previously by radiotherapy. If these efforts fail, chemotherapy is unlikely to result in cure. PMID- 2323617 TI - Early invasive cervical cancer with pelvic lymph node involvement: to complete or not to complete radical hysterectomy? AB - The completion of radical hysterectomy in the face of pelvic lymph node involvement presents a dilemma for the surgeon. Some believe it is appropriate to abort the hysterectomy to avoid the excessive morbidity of combined treatment; others believe that completion of the hysterectomy enhances survival. This study was undertaken to define the impact of completing radical hysterectomy followed by adjuvant radiation therapy upon patient survival or pelvic control. Fifteen patients with stage IB and IIA invasive cervical cancer whose radical hysterectomies were aborted solely for reasons of pelvic lymph node involvement were compared to a control group of 15 patients matched for tumor size and number of lymph nodes involved whose radical hysterectomies were completed. Both groups were treated with radiation therapy postoperatively. Survival was not different between groups (P = 0.81). Unexpectedly, local control was slightly improved in the group treated by radiation only (P = 0.127). If radiation therapy is anticipated, completion of radical hysterectomy followed by radiation therapy appears to offer no advantage over radiation therapy with the uterus in place in patients with early-stage invasive cervical cancer and pelvic lymph node involvement. PMID- 2323618 TI - Morbidity and mortality of stapled anastomoses on a gynecologic oncology service: a retrospective review. AB - The Gynecologic Oncology Division performed 167 operations requiring intestinal resection during the period July 1, 1980 to May 30, 1989. Stapling instruments were utilized in 155 procedures and resulted in 204 anastomoses. Major morbidity occurred in 36 (23%) patients, including 17 (11%) deaths and (4.5%) fistulas. Minor morbidity, such as ileus and atelectasis, occurred in 46 (30%) patients. Intestinal surgery is required in approximately 10% of gynecologic oncology procedures, and is associated with significant major and minor morbidity, particularly in obstructed patients. PMID- 2323619 TI - Human immunodeficiency virus seroprevalence among cervical cancer patients. AB - Human immunodeficiency virus (HIV) infection and cervical neoplasia intimately share several epidemiologic factors, the most important being the role of sexuality in their prevalence. Recent reports have suggested a strong association between the two conditions. In Africa HIV transmission is predominantly heterosexual and there is no significant sex preference. The prevalence of cervical cancer is also high in Africa and may be rising. Two hundred African patients with cervical carcinoma in Nairobi, Kenya, were screened for HIV seropositivity by both ELISA and Western blot. A seroprevalence rate of only 1.5% was obtained. This was comparable to the 2% found in the general population but much lower than the 18-59% recorded in recognized high-risk groups. The background to these surprising results and their implications are discussed. PMID- 2323620 TI - Serum albumin: its relationship to marrow and renal toxicity from platinum-based combination chemotherapy. AB - One hundred and three patients treated with CAP chemotherapy were evaluated to determine the relationship between low prechemotherapy serum albumin (less than 3 g/dl) and low WBC nadir (less than 2000 cells/mm3). Additionally, the relationship of serum albumin to renal toxicity (delta serum creatinine) was examined. Low prechemotherapy serum albumin appears to be a marker for advanced disease, but does not appear to predict marrow or renal toxicity. PMID- 2323621 TI - Acute leukemias II. Prognostic factors and treatment strategies. PMID- 2323622 TI - Biochemical evidence for synergistic combination treatment with methotrexate and 6-mercaptopurine in acute lymphoblastic leukemia. PMID- 2323623 TI - Pharmacokinetics of folinic acid in children with acute lymphoblastic leukemia. PMID- 2323624 TI - Cellular pharmacokinetics of daunomycin in human leukemic blasts in vitro and in vivo. PMID- 2323625 TI - Synergistic cytotoxicity of cytosine arabinoside and mitoxantrone for K562 and CFU-GM. AB - High-dose cytosine arabinoside (Ara-C) plus mitoxantrone (MX) have proved to be effective in the treatment of refractory acute leukemia. The optimal sequence of drug administration was tested in a clonogenic assay with the leukemic myeloid cell line K562, and with CFU-GM of normal human bone marrow. The exposure times were 24 h for Ara-C and 1 h for MX with 1 h delay between incubations. Either order of the drugs and a wide range of drug concentrations were tested. Cytotoxicity was quantified by the survival fraction (fs) of colonies scored on day 7 (K562) or day 14 (CFU-GM). Drug synergism was evaluated by a cooperative index (CI). CI less than 1 indicates synergism, CI = 1 summation, and CI greater than 1 antagonism of the cytotoxic drugs. In K562 the sequence Ara-C much greater than MX was significantly more toxic (3.68 logs cell kill, CI = 0.02) than MX much greater than Ara-C (2.64 logs kill, CI = 0.31). The highest synergism was found by adding MX during the last hour of a 24 h Ara-C exposure. For CFU-GM, Ara C much greater than MX showed higher synergistic toxicity (2.24 log cell kill, CI = 0.23) than MX much greater than Ara-C (1.44 logs, CI = 1.11). The clinical high dose Ara-C/MX protocol was transformed into an in vitro model and tested on K562. The highest synergism was found after the sequence of 3 h Ara-C followed by 0.5 h MX after 8.5 h delay (1.73 logs kill, whole sequence 2.01 logs kill), thus supporting the clinically applied sequence. PMID- 2323626 TI - Mafosfamide induces less sister chromatid exchange in Ph-positive cells than in normal bone marrow. AB - The frequency of induced sister chromatid exchange (SCE) is a sensitive tool for the monitoring of DNA damage and has been shown to indicate chemotherapy resistance. Mafosfamide is presently used for the purging of bone marrow in autologous bone marrow transplantation in the treatment of acute leukemia. We studied the SCE-inducing effect of mafosfamide on leukemic cells of Philadelphia (Ph)-positive chronic myeloid leukemia (CML) as a model for leukemic cells. Corresponding data from normal bone marrow were analyzed for comparison. A positive linear correlation (r = 0.99, P = 0.0005) was found between the dose of mafosfamide and induced SCE in Ph-positive CML and normal bone marrow. The concentration of mafosfamide used was 0.1, 0.2, 0.4, and 0.8 micrograms/ml. Additionally, we analyzed five cases of CML and six cases of normal bone marrow. A significant difference in the frequency of induced SCE/metaphase was found between CML and normal bone marrow even after addition of 0.8 micrograms/ml mafosfamide. Also, spontaneous SCE was significantly lower in CML. Our data indicate a lower sensitivity of the leukemic cells to mafosfamide as shown by the induction of a lower frequency of SCE events. PMID- 2323627 TI - Prognostic significance of chromosome analysis in de novo acute myeloid leukemia. PMID- 2323628 TI - Chromosomal aberrations in childhood acute nonlymphoblastic leukemia. PMID- 2323629 TI - Cytogenetic study of 130 childhood acute nonlymphocytic leukemias. PMID- 2323630 TI - Prognostic significance of the karyotype in patients with primary myelodysplastic syndrome. PMID- 2323631 TI - Prognosis and DNA aneuploidy in children with acute lymphoblastic leukemia. PMID- 2323632 TI - Prognostic significance of eosinophilia in acute myelomonocytic leukemia in relation to induction treatment. PMID- 2323633 TI - Double intensive consolidation chemotherapy (ICC) for acute myeloid leukemia. PMID- 2323634 TI - Myelodysplastic syndromes: preleukemic or early leukemic conditions? PMID- 2323635 TI - Acute nonlymphocytic leukemia in adults: results obtained with TAD remission induction therapy. PMID- 2323636 TI - Minimal residual disease in acute leukemia: lessons learned from animal models. PMID- 2323637 TI - Mitoxantrone in the treatment of acute leukemia. PMID- 2323638 TI - Continuous infusion of mitoxantrone combined with high-dose cytarabine in refractory/relapsed acute myeloblastic leukemia and blast crisis of chronic myelogenous leukemia. PMID- 2323639 TI - Treatment of recurrent acute myelogenous leukaemia at a single centre over a 10 year period. PMID- 2323640 TI - Oral idarubicin in elderly acute leukemia and refractory anemia with excess of blasts. PMID- 2323641 TI - Magnetic resonance imaging follow-up in patients with acute leukemia during induction chemotherapy. PMID- 2323642 TI - Thrombin generation in acute myeloblastic leukemia. PMID- 2323643 TI - Toward improvement of therapeutic strategies in leukemia by amplification of the immune responses against leukemia. PMID- 2323644 TI - Acute megakaryoblastic leukemia (FAB-M7) in an infant presenting with orbital chloroma and meningeal involvement. PMID- 2323645 TI - Risk of leukemic transformation in two types of acquired idiopathic sideroblastic anemia. PMID- 2323646 TI - Treatment of advanced myelodysplastic syndromes: trend toward more aggressive chemotherapy? PMID- 2323647 TI - Chronic myelomonocytic leukemia: clinical data, morphological features, and outcome in 56 patients. PMID- 2323648 TI - Chemotherapy of acute myeloid leukemia of 35- to 60-year-old patients. PMID- 2323649 TI - Double marker analysis for terminal deoxynucleotidyl transferase and myeloid antigens in acute nonlymphocytic leukemia patients and healthy subjects. PMID- 2323650 TI - Treatment of adult acute lymphoblastic leukaemia. AB - Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6 mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy. PMID- 2323651 TI - Effective prevention of central nervous system leukemia with intrathecal methotrexate and intrathecal methotrexate, cytosine arabinoside, and hydrocortisone in childhood acute lymphocytic leukemia. PMID- 2323652 TI - Incidence and clinical implications of acute hybrid leukemia in childhood. PMID- 2323653 TI - Prevention of bacteremias caused by alpha-hemolytic streptococci by roxithromycin in patients treated with intensive cytotoxic treatment. PMID- 2323654 TI - Hepatosplenic candidiasis in acute leukemias. PMID- 2323655 TI - Effect of antifungal therapy on hematological recovery after intensive antileukemic chemotherapy. PMID- 2323656 TI - Lymphocyte contamination in leukocyte-depleted red cell and platelet concentrates obtained by filtration. PMID- 2323657 TI - Prospective study on the influence of disease or treatment on pituitary function in 31 children with acute leukemia and non-Hodgkin's lymphoma. PMID- 2323658 TI - Incidence of aseptic osteonecrosis following the therapy of childhood leukemia. PMID- 2323659 TI - Osteoporosis in children with leukemia: a potentially debilitating anomaly? PMID- 2323660 TI - Principles of supportive psychological care for patients undergoing bone marrow transplantation. PMID- 2323661 TI - Fibronectin in stomatitis therapy of leukemic children. PMID- 2323662 TI - Treatment of relapsed or refractory acute leukemia: comparison of two different regimens. PMID- 2323663 TI - Heterogeneity in protein patterns of CGL blast crisis cells: discrimination between lymphatic and myeloic lineages. AB - Studies on cell-membrane-bound proteins in the human hematopoetic system revealed that the expression of certain peptides is restricted to the differentiation lineage. We applied discontinuous polyacrylamide gel electrophoresis of triton X 114 lysates to identify such proteins for a new diagnostic approach in human leukemia. A polypeptide with an apparent molecular mass range of 24 kd (p24) was found predominantly in cells of chronic granulocytic leukemia (CGL), myeloic type of blast crisis, and normal granulocytes. The data presented here suggest a role of this protein in the biology of malignant cells in chronic granulocytic leukemia throughout the course of the disease. PMID- 2323664 TI - Bone marrow transplantation from histocompatible sibling donors for patients with acute lymphoblastic leukemia. PMID- 2323665 TI - Allogeneic and autologous bone marrow transplantation in acute leukemia: the Essen Experience. PMID- 2323666 TI - Allogeneic and autologous bone marrow transplantation for acute lymphoblastic leukemia. PMID- 2323667 TI - Influence of treatment modality, patient/donor characteristics, and disease stage on the risk of relapse after allogeneic marrow transplantation for acute leukemia. PMID- 2323668 TI - Comparison of allogeneic and autologous bone marrow transplantation for treatment of acute lymphocytic leukemia in childhood. PMID- 2323669 TI - High-dose chemotherapy with noncryopreserved autologous bone marrow transplantation for acute myeloid leukemia in first complete remission. AB - Seven patients with acute myeloid leukemia (AML) in first complete remission were treated with escalating high doses of cyclophosphamide, etoposide, and cytosine arabinoside (Ara-C). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored in blood bags in a refrigerator for 48-72 h at 4 degrees C and then reinfused over a central line. All patients had a full hematological recovery. The mean time of neutropenia (neutrophils less than 500/microliters) was 14 days (range 9-24 days), and the mean time of thrombocytopenia (platelets less than 20,000/microliters) was 9 days (range 7-11 days). The nonhematological toxicity was tolerable with mild to moderate nausea/vomiting, mucositis and diarrhea, and so far not dose-limiting. Six patients remain in complete remission 17+, 9+, 5+, 5+, 4+, and 1+ months after autotransplantation. One patient relapsed 8 months after autotransplantation. High-dose chemotherapy with noncryopreserved bone marrow autotransplantation may be useful as intensified consolidation for patients with AML in first complete remission. PMID- 2323670 TI - Bone marrow transplantation with a fixed low number of T-cells in the graft. PMID- 2323671 TI - Complotyping and subtyping of MHC class I gene products in haplotype determination for bone marrow transplantation. PMID- 2323672 TI - Complications of bone marrow transplantation in Chinese. AB - Forty-three patients with hematopoietic disease were treated with intensive chemotherapy and radiotherapy, followed by allogeneic bone marrow transplantation (BMT) from 28 HLA-identical and 10 one to two antigen haploidentical sibling donors and autologous BMT (5 cases). Of these cases, there were 21 with acute nonlymphocytic leukemia (ANLL), 5 with acute lymphocytic leukemia (ALL), 6 with chronic myelocytic leukemia (CML), 2 with Hodgkin's disease (HD), 8 with severe form aplastic anemia (SAA) and 1 with thalassemia. Complications of BMT were evaluated including acute graft-versus-host disease (GVHD), interstitial pneumonia (IP), veno-occlusive liver disease (VOD), abnormalities of liver function (LF), and alteration of hepatitis B virus (HBV) markers. In thirty-three patients who were followed up for more than 3 months, we found that the incidence of moderate to severe acute GVHD (9.1%) and IP (two cases, 4.7%) were low. No VOD occurred in our series. During the follow-up period, 27 out of 35 patients (77%) had high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, even up to 1000 U/liter; however, only one patient succumbed to a hepatitis related complication. Previous hepatic damage from HBV infection before BMT does not appear to increase the risk of posttransplant morbidity and mortality. PMID- 2323673 TI - Interleukin-1 production in childhood acute lymphoblastic leukemia during chemo- and radiotherapy according to BFM (Berlin-Frankfurt-Munster) protocol. PMID- 2323674 TI - Colony-stimulating factors (rhG-CSF, rhGM-CSF, rhIL-3, and BCGF) recruit myeloblastic and lymphoblastic leukemic cells and enhance the cytotoxic effects of cytosine-arabinoside. AB - Prognostic models for acute myeloid and lymphoid leukemias are presented that demonstrate that cell kinetic quiescence in acute leukemia is associated with poor response to chemotherapy, short remission duration, and survival. Recruitment of cells into the cell cycle should therefore enhance cytotoxic effects of cell cycle - specific chemotherapeutic agents. We previously demonstrated recruitment of myeloid leukemic cells by cytokines. We have now investigated whether recruitment can be used to increase cell killing by cytosine arabinoside (Ara-C). Blast cells from 16 acute leukemias were stimulated with cytokines as follows: 13 acute myeloid leukemias (AML) and 3 chronic myeloid leukemia (CML) in blastic phase (1 lymphoid, 2 myeloid) were treated with recombinant human granulocyte colony stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony stimulating factor (rhG-CSF, AMGEN, 500 U/ml each), and recombinant human interleukin-3 (rhIL-3, IMMUNEX, 20 ng/ml), alone and in combination. After 48 h, at the time of maximal DNA synthesis, Ara-C (10(-3) M) was added and cell counts, cytokinetics (DNA/RNA, DNA/bromodeoxyuridine and DNA/Ki67 flow cytometry), and cell viability/clonogenicity (fluorescein diacetate/propidium iodide exclusion flow cytometry) were investigated. In all 13 cases of AML recruitment was found; in 6 of these cases over a three fold increase in S phase (P = 0.008) and a significant (P = 0.004) depletion of G0 was demonstrated. In 9 of 13 patients with AML, the effect of Ara-C was investigated, and in 3 of 5 patients with over three fold increase in S phase, Ara-C toxicity was enhanced. None of the patients with less than a three fold increase in S phase and no demonstrable recruitment from G0 had increased Ara-C cytotoxicity. Ara-C cytoreduction was paralled by reduction in clonogenicity as demonstrated by fluorescein diacetate/propidium iodide (FDA/PI) flow cytometry. Four samples of acute lymphoblastic leukemia (ALL) were treated with low molecular weight B-cell growth factor (15 kDa) and recruitment of aneuploid cells from G0 to G1 was found in all patients (from 19.3% to 84.9%). These results indicate that recruitment of leukemic cells is inducible by cytokines and that the cytotoxicity of cell cycle specific drugs such as Ara-C can be increased. This concept is presently being tested in vivo. PMID- 2323675 TI - Determination of soluble interleukin-2 receptors after bone marrow transplantation. PMID- 2323676 TI - Dependence of serum erythropoietin level on erythropoiesis in leukemia. AB - The dependence of the serum erythropoietin (Epo) level on the blood hemoglobin concentration was compared in patients suffering from leukemia and ulcerative colitis. In leukemia, the level of immunoreactive and bioactive Epo was generally much higher than in ulcerative colitis at comparable degrees of anemia. The highest Epo values were found in patients with severe bone marrow insufficiency of erythropoiesis. These findings support the hypothesis that the plasma level of Epo depends not only on the hemoglobin concentration of the blood but is also influenced by the proliferative activity of the erythron. PMID- 2323677 TI - Transferrin derivatives with growth factor activities in acute myeloblastic leukemia: an autocrine/paracrine pathway. PMID- 2323678 TI - Fibrinogen Barcelona II: a new case of A alpha 16 Arg----His substitution. AB - We describe a new congenital dysfibrinogenemia: fibrinogen Barcelona II in 8 members of a family with no major bleeding or thrombotic tendency. Incubation of this fibrinogen with thrombin at low concentration releases half of the expected normal fibrinopeptide A (FPA) and with some delay it releases an abnormal FPA. Abnormal FPA was purified and sequenced and showed a change in the normal amino acid sequence: arginine in position 16 has been substituted by a histidine. This is another case of dysfibrinogenemia in which A alpha 16 Arg----His has been identified as the cause of abnormal behavior of the fibrinogen molecule. PMID- 2323679 TI - Algorithm for short-term prescription of phenprocoumon. AB - Data from the start of anticoagulation therapy using the coumarin derivative phenprocoumon were obtained retrospectively for 101 patients, and the correct long-term maintenance dose (MD) of the drug was determined. The average loading dose was 23.2 +/- 7.8 mg and the average MD 2.14 +/- 0.99 mg. The physician's prescription on discharge tended to underestimate the true MD by 0.29 +/- 0.64 mg. Significant positive correlations with MD were noted for loading dose and weight and negative correlations for age, serum creatinine, initial prothrombin ratio, and length of treatment pause (days) for patients receiving an excessive loading dose. Using stepwise variance analysis, an algorithm was obtained that predicted the MD: MD = -0.7 + loading dose/10 - treatment pause/7 - age/60 + initial prothrombin ratio. The accuracy (0.02 +/- 0.54 mg) was similar to that of the discharging physician. The algorithm required an average observation period of 5.4 days and the physician's estimate 12.4 days. It is suggested that the use of the algorithm would lead to shorter hospitalization without loss of treatment accuracy. PMID- 2323680 TI - New possibilities for platelet shape change evaluation using the laser rheoaggregometer. AB - The study of aggregation functions in blood platelets can at present be undertaken in vitro by measuring variations in intensity of transmitted light or electrical impedance change. These two methods allow only a general approach to the aggregation process. The laser rheoaggregometer was constructed to study early morphological modifications induced when the platelets are activated before aggregation. The results obtained are in keeping with the laws of light scattering and allow the measurement of platelet shape change. PMID- 2323681 TI - Thrombin activity and oral anticoagulant therapy: a further evaluation. PMID- 2323682 TI - Vitamin K1 levels and coagulation factors in healthy term newborns till 4 weeks after birth. AB - Vitamin K1 serum levels were assessed by means of an off-line multidimensional liquid chromatography in 18 mothers, shortly after delivery, and in their healthy term infants. Umbilical cord and venous blood samples were assayed up to 4 weeks of life. Concurrently, levels of coagulation factors II and X, antithrombin III and platelets were established. Although the detection limit of the assay was as low as 22 pg/ml, vitamin K1 concentration appeared to be still beyond that level in cord blood or in newborn serum within 30 min after birth, whereas vitamin-K dependent coagulation factors are already at a level of 40%, without evidence for the presence of descarboxy prothrombin, in any of the investigated neonates. After 3 days, breast-fed neonates had lower vitamin K1 levels than formula-fed infants (0.76 and 1.44 ng/ml, respectively). The levels of the vitamin-K dependent coagulation factors II and X, however, were comparable, regardless of the kind of feeding. After 28 days, breast-fed neonates had even lower vitamin K1 levels (0.49 ng/ml, while the formula-fed infants showed higher vitamin K1 levels (4.45 ng/ml). But even then, the levels of vitamin-K-dependent coagulation factors II and X were comparable, regardless of the kind of feeding. From this we conclude that the serum levels of vitamin K1 in formula-fed neonates exceed those of breast-fed infants from the moment of feeding (24 h and later) without a concomitant rise in vitamin-K-dependent coagulation factors. A relationship between vitamin K1 levels and vitamin-K-dependent coagulation factors could not be established in healthy term breast-fed or formula-fed infants. PMID- 2323683 TI - Fifth Congress of Czechoslovak Immunologists. Plzen, July 5-9, 1988. Abstracts of workshops and posters. PMID- 2323684 TI - Behavioral development and socialization of infants in a free-ranging group of howling monkeys (Alouatta palliata). AB - A 22-month field study was carried out on free-ranging mantled howlers in Costa Rica. Six female and 5 male infants were observed systematically from birth until they died, left the group, or the study ended. Interaction patterns, activity patterns, and proximity data were analyzed from 703 h of focal observations and 753 h of ad lib observations. Developmental trends in weaning and nonmother care were associated with mothers' feeding patterns, suggesting an increase in maternal feeding efficiency. As howler immigration patterns resulted in groups of adults of low relatedness, analyses based on social bonding or kin selection were inappropriate, and socialization patterns instead appeared to prepare howler infants to respond predictably in an adult world. Females, which were more sociable as adults, were also more sociable as infants, initiating interactions and reacting positively. They also exhibited less weaning stress than males. Males, which were forced out of the group sooner, remained solitary longer, and primarily interacted with adult females as adults, were forced to be independent sooner, reacted negatively to interactions, and ceased interacting with adult males by 3 months of age. Ecological constraints on development could not be determined from this study, although there was no evidence for developmental trends being influenced by predator stress. PMID- 2323685 TI - Chimpanzee use of a tool-set to get honey. PMID- 2323686 TI - Acquisition of fertilizing capacity by chimpanzee sperm. PMID- 2323687 TI - Social relations in groups of the black-capped capuchin (Cebus apella) in captivity. Interactions of group-born infants during their second half-year of life. AB - During the second half-year of life, capuchin monkey infants maintain close contacts to kin-related animals. Apart from these contacts, they frequently interact with other infants and juveniles 1 year older. During this period of life the 'peer phase' begins in the life of the infants. Furthermore, gender differences, especially in respect to social play, become obvious. PMID- 2323688 TI - Diet and feeding behaviour of samango monkeys (Cercopithecus mitis labiatus) in Ngoye Forest, South Africa. AB - The samango monkey occurs at the southern limit of the range of Cercopithecus mitis. Greater climatic seasonality at this latitude results in more predictable fruiting patterns. In addition, there are no diurnal sympatric primate frugivores. Under these conditions, the diet and feeding strategies of samango monkeys would be expected to differ notably from those of central or east African C. mitis subspecies. Contrary to these expectations, the preliminary observations reported here indicate that diets of samango and blue monkeys differ only superficially in the proportions of items eaten. Similarities in feeding behaviour are especially marked during the dry season period when fruit is not abundant. Both samango and blue monkeys tend to be less selective in their choice of food species and to eat available food species regardless of their energy content; a shift toward less nutritious items such as leaves is also noted. Feeding behaviour during the summer wet season is characterized by the selection of fruits with high-energy values. A high proportion of visits by the monkeys to areas of greater food availability suggests a concentration of feeding effort in food patches and the selection of higher energy food species within patches. PMID- 2323689 TI - Morphological basis of arm-swinging: multivariate analyses of the forelimbs of Hylobates and Ateles. AB - Field and laboratory studies of arm-swinging in gibbons reveal its singularity even compared to spider monkeys. On the basis of principal components and discriminant analyses of size-corrected forelimb variables, this study confirms their morphological uniqueness and the more generalized nature of the spider monkey forelimb. Long forearms, well-developed scapular spines, and sagittally thicker radial shafts are features associated strictly with gibbon arm-swinging. On the other hand, large humeral heads, projecting medial epicondyles, and axially elongated scapulae, traditionally regarded as arm-swinging traits, are probably more important for climbing. PMID- 2323690 TI - [The ablation behavior of various corneal layers]. AB - The difference in structure of the corneal layers leads to an inhomogeneous reaction to photoablation with 193 nm excimer laser light. This is important for the calculation of photorefractive keratectomy (PRK) where only a thin layer (10 50 microns) of the cornea must be removed. Therefore, the ablation rate for the Bowman zone is 2.5 times lower than that for corneal stroma; the same value is found in Descemet membrane. In contrast, the ablation rate of the epithelium is 1.5 times higher. Based on these data it will be possible to achieve high precision with PRK. PMID- 2323691 TI - [Clinical types of immunologic transplant reactions following perforating keratoplasty]. AB - The incidence of allograft rejection was determined for 740 penetrating keratoplasties performed between 1980 and 1987. All 740 cases were followed up for at least 1 year. The reaction forms of allograft rejection were grouped according to biomicroscopic appearance. The incidence and progression of symptoms are described. Rejection types are subdivided into patients with favorable versus poor prognosis. Of the patients 37.9% demonstrated an immune response (including discrete forms). Clear reaction patterns within the two groups of patients became apparent when reaction variations were carefully differentiated. Epithelial immune reaction was found in 5.2%/10.5% and subepithelial infiltration in 1.7%/4.8% of the patients with favorable/poor prognosis. The largest disparity in frequency occurred in progressive endothelial reaction; 3.8% in patients with favorable versus 36.7% in patients with poor prognosis. Focal endothelial reactions occurred in both groups with comparable frequencies (14.1%/13.3%). The large percentage of immunological reactions, including late manifestations (approximately 12% after 1 year) and some with irreversible progression, warrants continuing efforts to treat and prevent this complication. PMID- 2323692 TI - [Non-freeze epikeratophakia (live epikeratophakia)]. AB - Instruments for the production of non-freeze epikeratophakia lenticules allow the surgeon to produce his own live lenticules from -35 to +25 dptr using the Barraquer-Krumeich-Swinger set. 29 myopic cases differ to the refractive target plus/minus 15% and reach contact lens visual acuity values after 2-5 weeks. 58 consecutive cases off epikeratophakia correction of aphakia result between 5 and 15% of the target. Optimal visual acuity is generally reached between 4 and 8 weeks postop. In 6 cases the epikeratophakia lenticule had to be removed and replaced. PMID- 2323694 TI - [A new strategy for automated static perimetry]. AB - The threshold of sensation in perimetry is a range where the probability of perception varies between 0% and 100%. The size of the range is dependent on sensitivity: it increases towards lower sensitivities. A new measurement strategy is presented where the luminance steps between the presentations vary according to the actual luminance level. Luminance steps and threshold variation are always kept in a constant relation. Thus, efficiency of perimetric measurements shall be improved. Already a single crossing of the threshold with dynamic steps gives reproducible results. In one field with 54 points, the mean standard deviation of 3 repeated measurements was 19% greater than that of a conventional 4dB-2dB double-crossing strategy, but the test time was 56% less. PMID- 2323693 TI - [Total average values of transient visual evoked cortical potentials in tests of the pressure tolerance of the optic nerve]. AB - Transient visually evoked cortical potentials were recorded during an artificial stepwise rise of intraocular pressure. At each pressure step one average was taken. The reversal rate was 1.9 Hz. Two groups of 30 healthy volunteers each were examined: in group one 25 sweeps were averaged and in group two 50 sweeps. Thus the recording time in group two was doubled compared to group one. When all subjects were examined the evoked potentials of the 30 subjects were averaged at each pressure step: the results was a "Grand Average" at the different pressure steps applied. The amplitudes of N2-P2 were plotted versus the intraocular pressure. It is seen that a not monotone or weakly monotone function in the amplitude/pressure curve is more clearly seen in the averages of 25 sweeps. We interpret this result as follows: a not monotone or weakly monotone behaviour is a sign of autoregulation in the optic nerve head. This sign is more clearly shown at a short recording time. The majority of healthy persons show autoregulation, the majority of glaucoma patients do not. According to the results presented here it is advisable to apply short recording times in clinical pressure tolerance testing of the optic nerve head. A short recording time enhances the accuracy of the test. PMID- 2323695 TI - [Clinical value of new tonometers]. AB - In a clinical study four different tonometers [a hand-held applanation tonometer (HAT), a tonometer that works according to the principle of Mackay-Marg and two noncontact tonometers (NCT A und NCT B)] were compared with respect to accuracy and precision. In a randomized sequence, two physicians took six measurements of both eyes of 99 patients using the four different instruments. The interval between the two measurements in one eye was 3 min. The correlations of repetitive measurements for one tonometer in one eye showed good results for HAT (r = 0.985, SD = 1.66 mmHg), but significantly worse values for the other three tonometers (Mackay-Marg type: r = 0.85, SD = 3.5 mmHg; NCT A and NCT B: r = 0.91, SD = 2.93 mmHg). To establish the accuracy, the pressure values of the Mackay-Marg type and NCT A and NCT B were compared with those of the well-established HAT. The results were as follows: Mackay-Marg type: r = 0.84, SD = 3.78 mmHg; NCT A: r = 0.86, SD = 4.55 mmHg; NCT B: r = 0.89, SD = 3.26 mmHg). We conclude that the three tonometers tested (one based on the Mackay-Marg principle and the other two on the non-contact principle) are not suitable for clinical and scientific use. PMID- 2323696 TI - [Raynaud syndrome following timolol-containing eyedrops]. AB - It has been well known for a long time that beta-adrenoreceptor-blocking substances may cause Raynaud's phenomenon in hands and feet if applied orally or parenterally. Nevertheless, vasospastic phenomenons of the "Raynaud"-type have never before been described following local administration. Now a Raynaud's syndrome found in a 58-year old patient, who had been treated for glaucoma with timolol (Chibro-Timoptol-eyedrops), leaves no doubt that there is a risk of systemic vasospasm in ocular application, too. An exposition test was carried out to prove the connection between the application of timolol eyedrops and Raynaud's syndrome. It did reveal that an initially already marginally prolonged warm-up time after exposition to cold water, as measured in the thermographic test, did relevantly get worse after timolol application. At the same time, no change in arterial systolic finger blood pressure could be demonstrated using Doppler sonography. The induction of Raynaud's syndrome by beta-adrenoreceptor-blocking eyedrops may depend on an individual disposition. PMID- 2323697 TI - [The pressure tolerance test--a new technic in the differential diagnosis of glaucoma]. AB - There can be a damage of optic nerve fibers without a known increase of intraocular pressure. This observation has led to the proposition to measure the pressure tolerance of the optic nerve head. An examination which is performing this task is feasible now with a recently introduced technique. In this paper clinically well defined borderline cases are presented in which the pressure tolerance test yields clinically valuable results. As shown paradigmatically the pressure tolerance test shows to be a valuable tool in the differential diagnosis of glaucoma. PMID- 2323698 TI - Microvascular network topology of the human retinal vessels. AB - A quantitative analysis of blood flow in the human retinal vessels requires a detailed picture of the microvascular network topology. In order to lay the foundation for a quantitative microcirculatory network analysis of the human retina, a novel technique for tissue preparation and network characterization was developed. After injection of hydrogen peroxide into the human bulb, the microvasculature was filled with oxygen produced by endothelial catalase and visualized after embedding in a mixture of cedar oil and gum damar. The vessel topology was documented in the form of photomicrographs, which permitted complete reconstruction of the microvasculature on transparent overlays. By considering the complete capillary system it was possible to divide the retinal network into dichotomous, asymmetric arteriolar and venular trees. The Strahler ordering method, which considers both dichotomous and side branching configurations, was selected and applied to analyze the retinal vascular trees, using the capillaries as the zero order reference vessels. The number of vessel segments was found to be an approximate logarithmic function of the order number, in accordance with Horton's law. Vessel lengths within each order were found to be log-normal distributed, and median lengths for different orders could be approximated by a 2nd degree polynomial curve. Diameters within each order could be approximated by a Gaussian distribution, and the mean values for different orders could be expressed by an exponential curve. These data provide the basis for conductance, pressure and flow computations within the retinal microvessels. PMID- 2323699 TI - [Morphometric analysis of age-dependent changes of the human ciliary body]. AB - Morphometric and stereologic techniques have been applied to human ciliary epithelium and bordering stroma of 31 (respectively 16) normal donor eyes aged 15 to 86, providing quantitative information on the age-related structural changes of ciliary body tissue. Aging appeared to result in a generalized widening of the stromal layer from 19.3 +/- 2.4 microns (10-20 years; n = 4) to 60.0 +/- 11.5 microns (80-90 years; n = 3) in ciliary processes and from 53.0 +/- 6.8 microns to 107.6 +/- 15.2 microns in the ground plate between ciliary valleys and ciliary muscle, a density increase of collagenous fibers from 39.3 +/- 4.9 to 83.5 +/- 14.6 fibers/microns 2 and a concomitant decrease in mean fiber diameter from 62.8 +/- 3.4 nm to 55.7 +/- 1.5 nm, a decline of stromal cell density from 31.4 +/- 1.8 to 9.6 +/- 1.0 cells/0.014 mm2, a progressive thickening of the inner and outer limiting membranes from 0.8 +/- 0.4 micron to 8.1 +/- 1.5 microns and 2.1 +/- 0.6 microns to 4.5 +/- 0.5 microns respectively as well as the endothelial basement membrane from 0.13 +/- 0.004 micron to 0.25 +/- 0.03 micron, a gradual widening of the perivascular space between capillaries and overlying pigment epithelium from 6.2 +/- 1.5 microns to 11.3 +/- 2.9 microns, an increase in number of fenestrations in the capillary endothelium from 39.0 +/- 8.5 to 69.0 +/ 7.0 pores/100 microns, and finally a continuous augmentation of degenerative elements including lipids, lipofuscin granules, and lysosomes from 1.5 +/- 0.06% to 7.2 +/- 0.6% within the non-pigmented epithelium (NPE) over the 71-year period studied. Regression analysis yielded a highly significant impact of age on these morphometric parameters, while the relative volumes of the remaining cell compartments of the NPE-cells revealed no statistically significant correlation with age. Rather, the variations in volume densities of Golgi bodies (0.34 +/- 0.25%; n = 16) and pigment granules (0.36 +/- 0.27%; n = 16) seemed to be random with respect to age, whereas the relative volumes of mitochondria (21.7 +/- 1.8%; n = 16) and RER (5.9 +/- 0.7%; n = 16) remained fairly constant indicating that the NPE-cells maintain their functional capacity with advancing age. Age-related reduction of aqueous humor formation therefore appears to be rather due to impaired fluid passage from vasculature to ciliary epithelium than to functional incompetency of the NPE. PMID- 2323700 TI - [Metastases of malignant extra-ocular tumors to the choroid. Diagnosis and fractionated radiotherapy]. AB - A total of 161 cases of choroidal metastases are reviewed. Breast or bronchial carcinomas are the most frequent primary tumors. One-third of the patients develop bilateral choroidal metastases. In 67% of all cases metastatic choroidal lesions were found in the posterior pole. Eighty-nine percent of all patients had a history of malignant tumor, in 11% of all patients choroidal metastasis was the first sign of a primary carcinoma elsewhere in the body. Sixty percent of all patients with choroidal metastases had additional other distant metastases at the time of diagnosis of choroidal involvement. The survival rate is poor: 50% of all patients with choroidal metastasis had died 1 year later. In 35% of all patients, choroidal metastases occurred despite prior systemic therapy with cytotoxic drugs or hormone therapy. In many cases the spontaneously course leads to irreversible loss of central visual acuity due to tumor growth, tumor necrosis or the complications of an exudative retinal detachment. Early fractionated external beam in radiation may prevent this outcome. The clinical course in 71 eyes following irradiation is reported. In 80% radiation therapy led to regression or eradication of the tumor, and a vision of at least 0.4 was maintained in 61% of the treated eyes. PMID- 2323701 TI - [Mirror effects caused by intraocular lenses]. AB - The PMMA intraocular lens has a far greater reflective capacity than the human lens. This reflective quality can be demonstrated through slit lamp biomicroscopy similar to the phenomenon producing the known Purkinje-Sanson mirror images. The arrangement of these images depends on lens centration and lens tilt. Since the introduction of lens implantation, such observations are clinically interesting, and until now this area has mostly been left unexplored. Furthermore, the highly reflective surface of intraocular lenses allows objects within the eye to be reflected. In this way, one can observe the pupillary margin of the iris "from the back" and the anterior chamber cells as a viral image due in the vitreous. The natural human lens does not produce this phenomenon, as its reflective capacity is low, a point in itself that is of special interest. Spectacles and optical instruments are treated today for the most part with a non-reflective surface to enhance contrast and avoid glare. Consequently, because of the high reflectivity of surfaces, glare may now be produced within the eye by intraocular lenses. On the other hand, technical attempts to reduce intraocular glare by artificial lenses should not interfere with the clinical interests of maintaining good biocompatibility. PMID- 2323702 TI - [Polishing of protein-coated intraocular lenses with the Nd:YAG laser]. AB - Extracapsular cataract extraction with implantation of posterior chamber IOLs has become a standard surgical technique with rare postoperative complications. However, in some patients, as a consequence of a particularly severe post operative inflammation, proteins and pigment can be deposited on the surface of the IOL in spite of medical treatment. In certain cases such deposits can be removed by using the Nd:YAG-laser. The indications, methods and the postoperative course of this treatment are discussed. PMID- 2323703 TI - [Electronic data processing at the clinic]. AB - Since 1 October 1986, all cataract, keratoplasty and glaucoma operations have been evaluated prospectively in the Department of Ophthalmology and Eye Hospital at the University of Erlangen-Nurnberg. The medical history data and preoperative status, intraoperative details and the postoperative course are standardized and stored. For each eye, the diagnosis is made according to the system called the "Erlanger Schlussel." The present status of the Erlanger Ophthalmological Documentation System for Cataract, Keratoplasty and Glaucoma surgery is outlined. The difficulties encountered when the project was started are pointed out. The importance of electronic data processing in research, teaching and patient care is discussed. PMID- 2323704 TI - [Artificial divergence surgery in congenital nystagmus]. AB - The treatment possibilities for nystagmus have been expanded by the addition of the artificial divergence procedure. This paper presents a study on 26 nystagmus patients with and without anomalous head posture and good binocular function and with detailed pre- and postoperative electronystagmographic records. All patients had been treated by artificial divergence by means of a prism base out before the operation. Seventeen patients showed significant improvement after the artificial divergence procedure. In 3 patients this procedure had to be combined with the classic Kestenbaum procedure. In 6 patients, the effect of artificial divergence with prisms was not satisfactory; thus, the Kestenbaum procedure was necessary. This study proves the effectiveness of the artificial divergence procedure alone or in combination with other procedures for treatment of anomalous head posture and the improvement of visual acuity and binocular vision. PMID- 2323705 TI - [Bacteremia in therapeutic endoscopy]. AB - In a prospective study of 70 patients undergoing therapeutic endoscopy, the incidence of bacteremia was established. It was observed in 20 after bougienage, 30% after the placement of an endoprosthesis, 15% after endoscopic sphincterotomy, and 25% after percutaneous biliary drainage. Although clinical symptoms were observed in only a few of these patients, perioperative antibiotic therapy is recommended in elderly patients with malignant diseases, diabetes mellitus, renal insufficiency or liver disorders. PMID- 2323706 TI - [Procedures for determining the diagnosis. Suspected primary gastrointestinal reflux disease. Remarks on the diagnostic diagram]. PMID- 2323707 TI - [The physician's obligation of confidentiality and HIV infection. Consent of the patient for informing the consultant is required]. PMID- 2323708 TI - [Emergency examination--a race with time. Vital function--Glasgow Coma Scale]. PMID- 2323709 TI - [Dyslipoproteinemias: treatment with lipid regulating drugs]. PMID- 2323710 TI - [Rehabilitation following reconstruction of the anterior cruciate ligament. The effect of a 6-week training program]. AB - Operations on the anterior cruciate ligament (ACL) represents a great challenge to the therapeutic team. Apart from early mobilisation, increasing attention must be paid to long-term after-care. Nineteen patients receiving reconstruction of the ACL underwent 6 weeks of training an average of 7.6 months after the procedure. At the start and end of the program, a dynamometric test (Dynamatik), and a function test, modified by Noyes, comprising a one-leg standing jump and hopping on one leg for six meters, were performed. Dynamometry revealed a clearly greater improvement in knee extension in the operated leg as compared with the non-operated leg, while the function tests revealed an improvement only in the operated leg. Correlation studies revealed no relationship between knee extension and function tests. For this reason, in addition to muscular strength, both training programs and after-care should take account also of the functional components of human locomotion, and should be carried out for a number of years. PMID- 2323711 TI - [Boerhaave syndrome]. AB - The diagnosis, differential diagnosis and possibilities for treatment of Boerhaave's syndrome are discussed in detail on the basis of a case report. Suggestions for the early detection of this very rare, life-threatening disturbance, and thus for a decisive improvement in the prognosis of this condition, are made. PMID- 2323712 TI - [Symptoms of delirium. 1: Clinical manifestations and diagnosis]. PMID- 2323713 TI - [Health examinations--still mainly in doubt. Health promotion for cost control?]. PMID- 2323714 TI - [Molecular analysis of the structure of the mutant NADH-cytochrome b5 reductase gene causing methemoglobinemia]. AB - Hereditary methemoglobinemia is a genetic disorder, transmitted as an autosomal recessive trait, characterized by NADH-cytochrome b5 reductase (b5R) deficiency. It is classified three types, erythrocyte, generalized, and blood cell types, in terms of tissues in which the enzyme is deficient. In attempt to analyse molecular mechanisms involved in the enzyme deficiency, we isolated b5R genes from the patient of hereditary methemoglobinemia, generalized type. 1. Sequence comparison of both b5R genes indicated that a thymidine at first position of codon 127 was altered to a cytidine, resulting in replacement of serine with proline. 2. Dot blot hybridization of the PCR-amplified DNA with allele-specific oligonucleotide probes showed that the patient was homozygous for this mutation. 3. Secondary structure prediction by the Chou-Fasman method showed that Ser-127 is presumed to be in an alpha-helix structure of a nucleotide-binding domain. 4. These observations showed that extension of the alpha-helix structure caused by replacement of Pro-127 affects the electron transport and the result is a generalized type of hereditary methemoglobinemia. PMID- 2323715 TI - [Intracerebral sites of action of estrogen on the sleep-wakefulness circadian rhythm in female rats]. AB - Effects of estradiol on the sleep-wakefulness circadian rhythm were studied in ovariectomized female rats under a 12: 12 light-dark schedule. In rats that were subcutaneously injected with 20 micrograms of estradiol benzoate (EB) or that had crystalline EB implanted into the third ventricle (III V), the total time of slow wave sleep (SWS) and paradoxical sleep (PS) in the night time was significantly decreased on the third day after the EB administration. The suppression of PS was more remarkable than that of SWS. Slight increases were observed in the total time of SWS and PS in the day time. These effects of estrogen on the appearance patterns of SWS and PS in the night and day time could be elicited in spayed rats after crystalline EB was implanted into the medial preoptic area (MPO) or the medial amygdala (mAMYG), but the implant into the latter proved less effective. Cholesterol implants into IIIV, MPO or mAMYG produced no change in the sleep wakefulness circadian pattern. Implantations of crystalline EB into the ventromedial hypothalamic nucleus or the dorsomedial thalamic nucleus were ineffective. These results indicate that MPO is probably the most effective site of estrogen on the sleep-wakefulness circadian rhythm of female rats. PMID- 2323716 TI - [Carcinoma complicating ulcerative colitis. Analysis of 8 Japanese cases]. AB - Eight patients with ulcerative colitis complicated by carcinoma were investigated histopathologically on their resected colorectal specimens. Four patients carried multiple tumors, another four patients a solitary tumor. The age at the onset of the colitis in patients with multiple carcinoma was younger in average (27 years old) than that in the patients with a solitary carcinoma (45 years old). Duration of the disease before surgery exceeded 10 years in six of the eight patients. A total of eight tumors of 10 mm or more in dimension were found in four multiple cases, six of them being located in the rectum. These tumors presented peculiar macroscopic features, such as villous, putty-like, nodular, or flat, and were advanced histopathologically, well or moderately differentiated adenocarcinomas in most cases. Six of the eight accompanied areas of epithelial dysplasia adjacent to the carcinoma, the border between carcinoma and dysplasia being vague in three of the six. All multiple cases showed active changes of ulcerative colitis or chronic inflammatory processes such as thickening of the muscularis mucosa, submucosal fibrosis and Paneth cell metaplasia in the crypts. Furthermore, all multiple cases had minute adenocarcinomas, less than 10 mm in diameter, the tumor being restricted to the mucosa or to the mucosa and submucosa. Four of the nine minute carcinomas coexisted with epithelial dysplasia, suggesting that carcinoma developed from dysplasia. On the contrary, the remaining carcinomas carried no dysplasic area with a possibility that carcinoma developed also from nondysplastic atrophic mucosa. Three of the four solitary tumors were conventional adenocarcinomas associated with chronic inflammatory or dysplastic change in the bowel. The specific stainings by lectins and high-iron-diamine (HID) gave no appreciable help in diagnosing the epithelial dysplasia because of unsettled staining results. A large number of argyrophil cells were present in dysplastic epithelia, although the number of such cells was small in carcinomas. PMID- 2323717 TI - The need for a national focus on health care productivity. PMID- 2323718 TI - Sharpening the focus on health system reform. PMID- 2323719 TI - Evaluating rural hospital consortia. PMID- 2323720 TI - A foundation's response to the need for better health statistics. PMID- 2323721 TI - Private foundations and government partnership opportunities. PMID- 2323722 TI - Living on the short side of the long run. PMID- 2323723 TI - Probing the perinatal paradox. PMID- 2323724 TI - Mandating employer coverage of mental health care. PMID- 2323725 TI - The role of sociology in health affairs. PMID- 2323726 TI - Registered nurse shortages: the road to appropriate public policy. PMID- 2323727 TI - Secretory protein 7B2. A novel tumor marker of medullary carcinoma of the thyroid. AB - Mean plasma concentrations of 7B2 in three patients with medullary carcinoma of the thyroid (MCT) (294 +/- 38 pg/ml) were significantly higher than those in age matched normal subjects (107.2 +/- 7.2 pg/ml, n = 11). The intravenous infusions of pentagastrin (0.5 microgram/kg) markedly increased the plasma concentrations of 7B2 as well as calcitonin in all three MCT patients but it caused no significant rise of the plasma 7B2 concentration in any healthy subjects. The peak times and rates of increase of plasma 7B2 concentrations were different from those of plasma calcitonin concentrations in MCT patients. The plasma 7B2 concentration in one of the patients with MCT showed a marked reduction and no further elevation from the pentagastrin infusion following a total thyroidectomy (preop. 226 pg/ml; postop. 112.1 pg/ml). The above evidence suggests that the increased levels of plasma 7B2 in MCT patients may be attributed to the release from parafollicular cells of thyroid. Therefore, 7B2 is considered to be clinically useful as a tumor marker of MCT. PMID- 2323728 TI - Free amino acids, copper, iron and zinc composition in sera of patients with thyrometabolic diseases. AB - Free amino acids together with copper, iron and zinc were measured in sera of 67 adult patients with thyrotoxicosis (n = 29) or hypothyroidism (n = 38). In contradistinction to the almost indifferences exhibited by the three metals, many amino acids displayed significant relationships with the thyrometabolic activity (mainly tyrosine and arginine with r values of 0.5 and 0.44, respectively). Additional analyses revealed certain patterns, between trace metals and amino acids, which conferred challenging difficulties to interpretation. Thus while zinc was associated positively with some amino acids (such as glutamic acid and alanine), copper correlated almost invariably in a negative manner with citrulline, alpha-amino-butyric acid, proline, glycine and valine. This new information should contribute to our knowledge of the complex metabolism of both trace metals and amino acids. PMID- 2323729 TI - Glucose-induced loss of exercise-mediated 3-0-methyl glucose uptake by isolated rat soleus and epitrochlearis muscles. PMID- 2323730 TI - Changes in skeletal muscle 3,5,3'-triiodothyronine nuclear receptors with thyroid status are dependent on energy balance. PMID- 2323731 TI - Monoamine oxidase A mediates iodotyrosine formation induced by monoamines in bovine thyroid particulate fraction. AB - Monoamines are able to increase the thyroid iodine organification in vitro. A predominance of the A form of monoamine oxidase (MAO) has been previously demonstrated to exist in bovine thyroid tissue. In the present study we have investigated the form of MAO that could be involved in the iodotyrosine formation induced by tyramine, 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PEA) in a bovine thyroid subcellular fraction. The relative capacity of these monoamines to generate H2O2 and to incorporate iodine into tyrosine has also been studied. The MAO A inhibitor clorgyline (10(-9) M) produced a strong inhibition on the iodotyrosine formation induced by tyramine, 5-HT and PEA. In contrast, only a slight reduction was observed with deprenyl as MAO B inhibitor. Among the three monoamines, tyramine produced the highest H2O2 generation and iodotyrosine formation. The lowest Km value obtained was for 5-HT and the highest for PEA. Regarding the Vmax, the lowest value was for 5-HT and the highest for tyramine. The amount of iodine incorporated to tyrosine was not equivalent to the H2O2 generated by the monoamines nor to that exogenously added. Our results indicate that in bovine thyroid tissue mainly the A form of MAO is involved in the monoamine metabolism. PMID- 2323732 TI - Weddellite calcification in the breast: eighteen cases with implications for breast cancer screening. AB - Breast tissue obtained from 18 of 246 women (7.3%) having localization biopsy for microcalcification contained crystals of Weddellite (calcium oxalate dihydrate). This was characterized by microscopic infra-red spectroscopy in three cases. Weddellite calcification was associated with benign lesions in 16 cases, but incidental atypical lobular hyperplasia and lobular carcinoma in situ were present, each in one case. Pathologists should be aware of this common non haematoxyphilic, birefringent form of breast micro-calcification. Its presence has implications for the examination of biopsy specimens resulting from breast cancer screening using mammography. PMID- 2323733 TI - Breast cancers with extremely high oestrogen receptor protein status. AB - Seventeen cases of primary and one case of metastatic breast cancer which expressed greater than 900 fmol oestrogen receptor sites per mg soluble protein were examined. All these patients were post-menopausal at the time of their presentation. These were a heterogeneous group of well-differentiated cellular breast carcinomas, comprising cases of invasive duct carcinoma with extensive tubular differentiation or with focal argyrophilia, tubulolobular carcinoma, lobular carcinoma of mixed type containing abundant intracytoplasmic lumina, papillary carcinoma and type B colloid carcinoma. There was very little tumour necrosis. Nodal metastasis, tumour size and host inflammatory response did not appear to show any relationship with oestrogen receptor status. The patients, apart from two who died from other causes, remain alive (Fisher's exact test, P less than 0.01). In contrast, 17 randomly selected cases of oestrogen receptor negative breast cancer in the same study period were focally necrotic, poorly differentiated invasive duct carcinomas. Six patients died from metastatic disease, seven were alive and well, one was alive with metastatic disease, one was lost to follow-up and two died from diseases unrelated to breast cancer. PMID- 2323734 TI - Infected cells and immune cells in the gastrointestinal tract of AIDS patients. An immunohistochemical study of 127 cases. AB - Human immunodeficiency virus (HIV) proteins were detected by immunohistochemistry in the duodenal and rectal mucosa of 30% of 127 AIDS patients studied. HIV infected cells were present in the lamina propria in 95% of the positive biopsies. They were immune cells, either isolated lymphocytes and macrophages (1 4 per positive biopsy) or dendritic reticulum cells forming a network in the germinal centres of mucosal lymphoid follicles. HIV proteins were not found in the duodenal epithelium or in the superficial rectal epithelium. In two cases (5% of the positive biopsies), they were found in rectal glands: the HIV-infected cells could be either epithelial cells or immune cells. This study confirms that the gut can be a target organ for HIV and that HIV is mainly carried by gut immune cells. The phenotypic study of lymphoid populations and macrophages in the gut mucosa of AIDS patients showed an inverse CD4/CD8 ratio in the lamina propria, compared with normal controls. This was independent of the presence of HIV proteins and is probably responsible for the appearance of opportunistic infections in the mucosa. An increase in activated macrophages was also noted in the mucosa of AIDS patients. PMID- 2323735 TI - Gastric dysplasia: inter-observer variation, sulphomucin staining and nucleolar organizer region counting. AB - Gastric dysplasia is regarded as a pre-neoplastic lesion and is generally believed to have higher potential for malignant transformation with increasing grade. To obtain consistency in diagnosis and management, reproducible diagnostic criteria are needed. We have used the classification system of the International Study Group on Gastric Cancer--ISGGC and investigated the interobserver variation in histological diagnosis. A Kappa statistic of 0.579, which reflects moderate agreement, was obtained for variation between two experienced pathologists. The prevalence of type III intestinal metaplasia was studied and found to occur in 55% of dysplastic areas, but in only 9% of hyperplastic areas (P less than 0.01). In addition, the correlation of mean nucleolar organizer region (AgNOR) counts with diagnostic categorization was investigated. A significant inter-observer variation was found between an experienced pathologist and a postgraduate student and only one of the observers obtained statistically significant separation of mean AgNOR counts between the categories of high-grade dysplasia, low-grade dysplasia, atypical hyperplasia, simple hyperplasia and normal. PMID- 2323736 TI - Immunostaining of antral gastrin cells is quantitatively increased in Heliobacter pylori gastritis. AB - The amount of gastrin-like immunostaining in gastrin (G) cells of the antral mucosa was quantified using a computer-assisted method of measuring immunoreaction product. Biopsies from 25 patients without Heliobacter-like organisms and 60 patients with varying degrees of infection were immunostained for gastrin. Twenty-five G cells from each patient were measured both subjectively and by image analysis. Gastrin-like immunoreactivity was found to be significantly increased in the presence of Heliobacter-like organisms. PMID- 2323737 TI - Lymphocyte predominance Hodgkin's disease--an immunohistochemical study. AB - Lymph node biopsies from 57 local and referred cases, previously diagnosed at Southampton between 1978 and 1987 as lymphocyte predominance Hodgkin's disease were examined using the monoclonal antibodies MT1, UCHL1, L26, LN-1, E29/68 (EMA), Leu-M1 (CD15) and Ber-H2 (CD30). Of the 34 cases with a nodular architecture, 21 (19 male, two female) contained polylobated Reed-Sternberg cell variants with a B-cell phenotype, which lacked expression of CD15. In all cases, the polylobated cells showed positive staining with L26 and LN-1. Six cases expressed EMA and three showed positive staining with Ber-H2. Two cases lacking polylobated cells were reclassified as reactive follicular hyperplasia with progressive transformation of germinal centres. The remaining 11 cases had an atypical immunophenotype and were reclassified, mainly as mixed cellularity Hodgkin's disease. In six cases, the lymph node architecture showed a mixture of nodular and diffuse growth patterns. Five of these cases contained polylobated cells with the typical morphology and immunophenotype of those seen in nodular lymphocyte predominance Hodgkin's disease. The sixth case contained cells expressing CD15, and was reclassified as nodular sclerosing Hodgkin's disease. Of the fifteen biopsies with a diffuse architecture, four contained polylobated B cells lacking expression of CD15. These were considered to be diffuse lymphocyte predominance Hodgkin's disease. The remaining 11 cases were reclassified as either Hodgkin's disease, mixed cellularity or as T-cell lymphomas. PMID- 2323738 TI - Diphtheria with a difference--a rare Corynebacterium fatality with associated apoptotic cell death. AB - A case of infection with Corynebacterium ulcerans (C. ulcerans), resulted in the sudden death of a previously healthy 73-year-old woman. Death from Corynebacterium diphtheriae (C. diphtheriae) infection is well-documented. Fatalities following infection with C. ulcerans are unreported; this would appear to be the first documented death due to such infection. PMID- 2323739 TI - T-cell lymphoma associated with human immunodeficiency virus (HIV) infection. AB - A patient with pneumococcal septicaemia and serological evidence of infection with human immunodeficiency virus (HIV) presented with a peripheral T-cell lymphoma. As far as we are aware this association has not been reported previously. PMID- 2323740 TI - Primary pleomorphic T-cell lymphoma of the spleen. PMID- 2323741 TI - Placental site nodule. AB - The immunohistological features of a case of placental site nodule, a cytologically alarming but clinically benign lesion, are reported. PMID- 2323742 TI - Unusual extraskeletal myxoid chondrosarcoma in a child. PMID- 2323743 TI - Incidence and distribution of carcinoma in situ in testes removed for germ cell tumour: possible inadequacy of random testicular biopsy in detecting the condition. AB - A total of 127 testicular specimens with germ cell tumours were stained immunohistologically for placental alkaline phosphatase to investigate the presence and topographic distribution of carcinoma in situ cells adjacent to the invasive tumours. Carcinoma in situ was detected in 72% of the cases. In 60% of the cases positive for placental alkaline phosphatase the distribution of carcinoma in situ was not diffuse, as claimed in the literature, but focal. Clinicians screening for carcinoma in situ by only one random biopsy have, therefore, to be aware of possible false negative results. PMID- 2323744 TI - Multinucleate giant stromal cells in testicular atrophy following oestrogen therapy. PMID- 2323745 TI - Angiomyoma of the uterus in a patient with tuberous sclerosis. PMID- 2323746 TI - Primary angiosarcoma of the uterus: a case report. PMID- 2323747 TI - CON 'tailoring' comes to a head in Kentucky. PMID- 2323748 TI - Protecting your hospital against vendor bankruptcy. PMID- 2323749 TI - Public hospital markets outpatient care, cuts ED use. PMID- 2323750 TI - Candid discussion is aim of JCAHO's CEO exit conference. PMID- 2323752 TI - HAS/Monitrend II nursing cost and salary data. PMID- 2323751 TI - Effective advocacy is critical for the '90s. PMID- 2323753 TI - Business leaders bring their clout to Washington. AB - Big business has always been opposed to government interference in its affairs. But now, besieged by the high cost--increasing at an annual rate of 20 to 30 percent--of health benefits for employees, their families, and retirees, a significant number of major corporate executives are seeking greater government involvement in finding a solution to the problem. Interest in health care policy decisions is so high that business leaders are participating in special health care commissions as members or by providing testimony. Some corporations even send company advocates to Washington, DC, to track and influence health care policymaking. What exactly do these corporate leaders want? They are not all in agreement about the degree of government involvement that is necessary or desirable. Nevertheless, they do have strong opinions about delivery of health care at the local level. PMID- 2323754 TI - Hospitals win healthy margins by following business basics. AB - In today's tough economic environment for hospitals, what separates the winners from the losers? An analysis of the sixth annual CEO Survey, jointly sponsored by Hospitals and Hamilton/KSA, an Atlanta-based consulting firm, points to some answers. Hamilton/KSA cross-tabulated the survey to see what factors were associated with increasing and decreasing margins. PMID- 2323755 TI - Nursing restructuring renews focus on patient-centered care. AB - This year, the JCAHO will issue revised nursing standards that make the patient the center of care. This new focus is a significant switch from the existing standards, and nursing experts predict that the structures of all other direct patient care jobs in the hospital will be affected. PMID- 2323756 TI - Hospital closure won't always help competitors. PMID- 2323757 TI - Contract management. AB - From the employee cafeteria to the emergency department all the way to the executive offices, there are contract firms that will provide hospitals with a spectrum of services. But how do health care executives decide whether this is the right option for their hospital? PMID- 2323758 TI - Hotel services adjust to outpatient care. PMID- 2323759 TI - Contract firms trim business costs. PMID- 2323760 TI - Medical firms make clinics efficient. PMID- 2323761 TI - Training is key to organizational change. PMID- 2323762 TI - New job title links business with patient care. PMID- 2323763 TI - Special issue on quantitative traits and population structure. PMID- 2323764 TI - Biochemical heterozygosity and morphological variability: interpopulational versus intrapopulational analyses. AB - The literature is replete with articles suggesting the existence of a relationship between variability at biochemical loci and morphological variation in various animal populations, including humans. With few exceptions these previous studies have utilized an interpopulational approach by examining levels of heterozygosity between modal and extreme phenotypes, typically by use of analysis of variance. Here we consider these purported relationships in a midwestern Mennonite population (n = 890) by correlating individual biochemical heterozygosity and deviation from the mean for anthropometric traits. The results of this intrapopulational correlation indicate that (1) with protection for multiple tests, there are few significant correlations and these have low R2 values, and (2) males and females show different patterns of correlation (males negative, females positive). Based on these findings, the results of earlier studies are in question because nonprotected alpha values are used for multiple tests and heterozygosity is calculated on the basis of a few highly heterozygous blood group systems and is assumed to be representative of the heterozygosity for the entire genome. In general, no evidence is found to support the concept of a direct relationship between biochemical heterozygosity and morphological variability. PMID- 2323765 TI - Isolation by distance and correlation analysis of distance measures in the study of population structure: example from the Island of Hvar. AB - Assessment of the population structure on the island of Hvar is based on the analysis of Malecot's isolation by distance model. We have tested the fit of the model by regression analysis of different measures of similarity (genetic kinship) and distance [Hamming's HSM distance for linguistic data; Mahalanobis's D2 distances for anthropometric head and body dimensions, radiogrammetric dimensions of metacarpal bones, physiological (cardiorespiratory) traits, and quantitative dermatoglyphic properties of the digitopalmar complex; and Edwards's E2 for frequencies of erythrocyte antigens]. Good fit of the model for linguistic and anthropometric data, which was demonstrated in previous studies on other eastern Adriatic populations, is confirmed. We compared parameters of the model with those already published for various populations in the eastern Adriatic and other parts of the world. We also evaluated the pattern of correlations between different measures of geographic, biological, and sociocultural distances through principal components analysis and interpreted the results within the context of microevolutionary theory and the population's ethnohistorical background. PMID- 2323766 TI - Effects of population structure on within-group variation in the Jirels of Nepal. AB - The impact of population structure on phenotypic differentiation is most frequently considered in terms of between-subdivision variation. However, the demographic and social structures of a population also induce changes in within group variation. We analyze the intragenerational dynamics of within-group variation for the Jirels, a tribal population of eastern Nepal. In the analyses we utilized age- and sex-corrected cranial measures (head length, head breadth, bizygomatic diameter, minimum frontal diameter, and head circumference) available for 526 adults (ages 15-54 years). We used a multivariate measure of variance, the standardized generalized variance, to assess levels of within-village variability, quantifying the sampling variance for this statistic by using a jackknife methodology. To generate null expectations of within-group variation, we used permutation procedures, which permit robust testing of significance without distributional assumptions. We also compared the within-birthplace variation in adults to the observed within-residence variation to examine migration effects. Contrary to expectation, some villages with high rates of in migration have less variability than those with few migrants. When differences between the sexes at birth are controlled for, females in some villages exhibit greater variance than males, reflecting known differences in sex-specific dispersal. PMID- 2323767 TI - Quantitative traits in relation to population structure: why and how are they used and what do they imply? AB - I describe the basic ingredients of a population structure analysis and the rationale for using polygenic quantitative traits in such analyses. The complexity of inheritance and the population dynamics of quantitative traits, however, imply that inferences regarding population structure based on such traits must be evaluated with appropriate cautions. Although many studies of quantitative traits in relation to population structure analysis underscore the importance of gene flow between subpopulations, I show that the role of selection in the evolution of a quantitative trait and its relationship to the inferred population structure cannot be overlooked. Finally, I review some recent advances in human quantitative genetic methodologies that can be used profitably in population structure analysis. PMID- 2323768 TI - Population structure analysis using polygenic traits: estimation of migration matrices. AB - Many studies of subdivided populations have attempted to determine the underlying migration rates that generate observed patterns of genetic differentiation. Most previous analyses have yielded only qualitative inferences about migration. In this paper I present a new method for estimating the full migration matrix from information on polygenic trait variation. The method employs multivariate quantitative genetic theory to provide a matrix formulation of the expected covariance structure in multigenerational subdivided populations for which information is available at different points in the life cycle. I develop a restricted maximum likelihood technique (REML) to take account of this additional life-cycle information and to estimate both the migration matrix and the ratio of effective population size to census size. To make the problem computationally tractable, the migration matrix is modeled as a log-linear function of a few covariates, such as subdivision size and geographic distance. I apply the technique to data on dermatoglyphic ridge counts for 1015 individuals of the Jirel population of east Nepal, considering two different age cohorts. In the adult cohort (individuals over 21 years of age) I examine data by both birthplace and residence and for the subadult cohort (under 21 years of age), by birthplace. Results from the REML technique reveal that the best-fitting migration model is a finite island model with an estimated endemicity of 0.730 +/- 0.105 and an estimated ratio of effective size to census size of 0.287 +/- 0.095. Both estimates are reasonable given known demographic data. In addition, Fst values predicted by the migration model are concordant with REML estimates obtained directly from the dermatoglyphic variation. PMID- 2323769 TI - Analysis of prehistoric biological variation under a model of isolation by geographic and temporal distance. AB - Biological distances calculated between archeologically recovered human skeletal collections are often used to assess the effects of temporal and spatial distance on subpopulation divergence. Although there are many previous empirical studies that examine skeletal material arrayed across time and/or space, the theoretical expectations for temporally or spatially related variation in biological characteristics have not been formally developed. In this paper I present the infinite island model, the unidimensional stepping-stone model, and the migration matrix method in forms that allow prediction of the genetic distance between groups separated by a given spatial and temporal lag. These models demonstrate that, if there is isolation by geographic distance, then the correlation between genetic and spatial distance (controlling for temporal distance) should be positive and the correlation between genetic and temporal distance (controlling for spatial distance) should be negative. I use observations of nonmetric traits in a sample of prehistoric crania from west-central Illinois to demonstrate the expected relationships among biological, temporal, and spatial distance. The results indicate that, once the effects of temporal trend are removed, biological and spatial distance are positively correlated and biological and temporal distance negatively correlated within this sample. PMID- 2323770 TI - Detection of differential gene flow from patterns of quantitative variation. AB - A major goal in anthropological genetics is the assessment of the effects of different microevolutionary forces. Harpending and Ward (1982) developed a model that aids in this effort by comparing observed and expected heterozygosity within populations in a local region. The expected heterozygosity within a population is a function of the total heterozygosity of the entire region and the distance of the population from the regional mean centroid of allele frequencies. Greater than average gene flow from an external source will result in a population having greater heterozygosity than expected. Less than average gene flow from an external source will result in a population having less heterozygosity than expected. We extend the Harpending-Ward model to quantitative traits using an equal and additive effects model of inheritance. Here the additive genetic variance within a population is directly proportional to heterozygosity, and its expectation is directly proportional to the genetic distance from the centroid. Under certain assumptions the expectations for phenotypic variances are similar. Observed and expected genetic or phenotypic variance can then be compared to assess the effects of differential external gene flow. When the additive genetic covariance matrix or heritabilities are not known, the phenotypic covariance matrix can be used to provide a conservative application of the model. In addition, we develop new methods for estimation of the genetic relationship matrix (R) from quantitative traits. We apply these models to two data sets: (1) six principal components derived from twenty dermatoglyphic ridge count measures for nine villages in Nepal and (2) ten anthropometric measurements for seven isolated populations in western Ireland. In both cases both the univariate and multivariate analyses provide results that can be directly interpreted in terms of historically known patterns of gene flow. PMID- 2323771 TI - Generational change in skin color variation among Habbani Yemeni Jews. AB - The Habbani Yemeni Jews were a religious isolate in Yemen for centuries. Since a bottleneck in the late eighteenth century the population, composed of six partrilineages, has steadily grown. Isonymy analysis of Habbani genealogies reveals a significant increase in lineage endogamy by the early twentieth century, suggesting that microdifferentiation of Habbani population genetic structure along the patrilineages was occurring. We examine reflectance data from a "parental" generation of 159 individuals studied by Hulse in the 1960s and reflectance data from an "offspring" generation of 243 individuals studied by Towne in the 1980s. A greater amount of interlineage skin color differences is found in the offspring generation than in the parental generation. This finding is consistent with what is known of the evolution of Habbani population genetic structure. PMID- 2323772 TI - Viral integration, fragile sites, and proto-oncogenes in human neoplasia. AB - To evaluate the trend of viral integration in the human genome, chromosomal localization of five DNA-containing viruses compiled from literature data was compared to the location of fragile sites and proto-oncogenes. A total of 35 regionally mapped viral integration sites from tumors and transformed cells were distributed over 19 chromosomes. Of the 35 integration sites 23 (66%) were at the bands of fragile sites, and 7 were one band away (20%). This statistically defines the correlation as highly significant (P = 0.0000183, Fisher's F-test). Five integration sites did not correspond to the location of a fragile site. Thirteen integration sites and proto-oncogenes mapped at the same bands (37%), 6 (17%) were one band apart, and at 16 integration sites (46%) no proto-oncogenes were localized (P = 0.00491). Eighteen viral integration sites, fragile sites, and proto-oncogenes (51%) were localized at the same bands or one band distant. This clustering of viral integration sites, fragile sites, and proto-oncogenes is statistically highly significant (P = 0.0000118), and indicates nonrandom viral integration in the human genome. PMID- 2323773 TI - Phenylketonuria mutation in Chinese haplotype 44 identical with haplotype 2 mutation in northern-European Caucasians. AB - DNA amplification with the polymerase chain reaction was employed to identify the phenylketonuria (PKU) mutation in Chinese PKU families. The amplified DNA was hybridized with oligonucleotides corresponding to the two most common mutant alleles, i.e., mutations associated with PKU haplotype 2 and 3 among Caucasians of northern-European ancestry. The results of analysis demonstrate that the mutation in Chinese haplotype 44 is a single-base substitution corresponding to the mutation associated with haplotype 2 in Caucasians, whereas the mutations of the phenylalanine hydroxylase gene in haplotypes 4, 7, 11 and 28 among Chinese do not correlate with either of the two mutations identified in northern-European Caucasians. PMID- 2323774 TI - Isolation and regional localisation of DNA sequences from a human chromosome 11 specific cosmid library. AB - A cosmid library has been prepared in the lorist-B vector from a mouse/human somatic cell hybrid containing region 11q23-11pter as the only human component. This chromosome region is stably maintained in the hybrid as a result of translocation onto one copy of mouse chromosome 13. Individual cosmids containing human DNA were isolated by their ability to hybridise with total human DNA, digested with either HindIII or EcoRI, and 33 individual unique sequences were identified. These fragments were then isolated and subcloned into the bluescribe plasmid vector. Regional localisation of these unique sequences was achieved using a panel of somatic cell hybrids containing different overlapping deletions of chromosome 11. The majority of the 33 mapped sequences derived from the long arm of chromosome 11. Two clones were located within the 11p13-p14 region, which is associated with a predisposition to Wilms' tumour. These probes supplement those already mapped to this chromosome and will assist in the generation of a detailed chromosome 11 linkage map. PMID- 2323775 TI - Chromosomal in situ hybridization of a Hodgkin's disease-derived cell line (L540) using DNA probes for TCRA, TCRB, MET, and rRNA. AB - The Hodgkin's lymphoma-derived cell line L540, which exhibits multiple marker chromosomes and a genotype characteristic of T-cell origin, showed expression of MET oncogene. L540 was studied by in situ hybridization for chromosomal rearrangements concerning the regions where genes for TCRA and TCRB chains, for MET oncogene, and for rRNA are located. All four genes were demonstrated to be involved in the formation of marker chromosomes. Especially remarkable was the participation of rDNA-bearing regions in two different translocations. PMID- 2323776 TI - Genetic differences in cystic fibrosis patients with and without pancreatic insufficiency. An Italian collaborative study. AB - To determine the number and frequency of mutations that occur at the cystic fibrosis locus (CF), we have examined the allele and haplotype frequencies of eight polymorphic DNA markers linked to CF in 163 Italian patients who were sub divided according to their clinical presentations. The distribution of haplotypes for the tightly linked polymorphisms KM.19 and XV-2c differ significantly between patients with and those without pancreatic insufficiency. The haplotype found most commonly in CF chromosomes occurs much more frequently in pancreatic insufficient than in pancreatic sufficient patients. Among the 19 pancreatic sufficient patients, 6 (31.6%) show at least one copy of the rare KM.19 = 1, XV 2c = 2 haplotype, as against 16 of 138 patients (11.6%) with pancreatic insufficiency. In addition, only 5 pancreatic sufficient patients (26.3%) are homozygous for the common 2.1 haplotype, as compared with 88 patients (63.8%) with pancreatic insufficiency. These findings support the hypothesis of allelic heterogeneity at a single locus in CF and suggest that different mutations underlie the presence or absence of pancreatic insufficiency in this disorders. PMID- 2323777 TI - In situ hybridization studies using a molecular probe that maps to Xq27-Zq28. AB - The locus DXS98, which is recognized by the sequence p4D-8, is closely linked to the FRAXA locus. In this study we present data that confirm the existing mapping data, sublocalizing this sequence to the Xq27 region immediately proximal to the fragile site at Xq27.3. PMID- 2323778 TI - Trophoblast glycoprotein recognised by monoclonal antibody 5T4 maps to human chromosome 6q14-q15. AB - Human X rodent hybrids were stained by indirect immunofluorescence with 5T4, a murine monoclonal antibody that recognises a 72 kdalton glycoprotein expressed by human trophoblasts and a very restricted range of adult tissues; they were analysed by flow cytometry. Concordance analysis supported by segregation data allowed assignment of the gene controlling glycoprotein expression (M6P1) to chromosome 6. Similar analysis with translocation hybrids gave a regional assignment to 6q14-q15. M6P1 is distinct from NT5, coding for 5' nucleotidase, which maps to the same region. PMID- 2323779 TI - Choroideremia associated with an X-autosomal translocation. AB - A patient with mild choroideremia has been shown to carry a balanced translocation between chromosome X and 13-46,X,t(X;13)(q21.2;p12). Loci (DXY21, DX232, DX233) shown to map to this region on the X chromosome and in some cases to be deleted in other patients with choroideremia are intact in the DNA from this patient. To our knowledge this is the first report of a translocation associated with choroideremia. One of the translocation chromosomes, derivative 13, free of the derivative X and normal X, has been isolated in a somatic cell hybrid. Because of the clinical association of the eye findings with chromosome interchange, we suggest that the breakpoint on the X is at or near the choroideremia locus. Further analysis of this translocation may be useful in cloning the choroideremia gene. PMID- 2323781 TI - Regional assignment of the human C1-inhibitor gene to 11q11-q13.1. AB - In situ hybridisation using a biotinylated 1.8 kb human cDNA clone in both normal and structurally abnormal chromosomes supports regional localisation of the gene for human C1-inhibitor to chromosome 11q11-q13.1. PMID- 2323780 TI - Isolation of a cDNA clone encoding a novel form of granzyme B from human NK cells and mapping to chromosome 14. AB - We have isolated cDNA clones from a human NK cell cDNA library that encode the serine protease granzyme B. Although the sequence of the entire coding region for the mature protein and the 3' untranslated region of the clone are identical to other cDNA isolates of this gene obtained from human T cell cDNA libraries, the 5' end of two clones is 103 bp longer than the previously described sequences and would encode a protein with a 54-amino-acid-long signal sequence. Experiments characterizing granzyme B mRNA suggest that transcripts that initiate at or before the 5' end of these clones comprise a detectable but infrequent class of granzyme B transcripts in NK and T cells. We have mapped this gene to human chromosome 14 in the region 14q11----14q32, distal to the T cell receptor alpha locus and proximal to the immunoglobulin heavy chain locus. The chromosomal location of this gene, together with the previously described high sequence homology between this gene and the mouse CTLA 1/ccp1 gene, make it likely that this is the human equivalent of the mouse CTLA1/ccp1. PMID- 2323782 TI - Hypoxanthine guanine phosphoribosyltransferase deficiency: nucleotide substitution causing Lesch-Nyhan syndrome identified for the first time among Japanese. AB - A previously undescribed nucleotide substitution at codon 51 (CGA to TGA) has been identified using the polymerase chain reaction technique in hypoxanthine guanine phosphoribosyltransferase (HPRT) cDNA; this is the first molecular evidence for a point mutation in a Japanese patient with Lesch-Nyhan syndrome. The present mutation is the 19th nucleotide substitution identified as a germ line mutation at this locus and the second mutation generating a stop codon. The position of the nucleotide substitution is exactly the same as a previously described mutation HPRTToronto, indicating for the first time that nucleotide substitutions at the same position in the sequence of HPRT can generate different mutant alleles, one causing a partial deficiency and the other a complete deficiency. Although the type of nucleotide substitution is different between the two cases, a single base position has twice become the target of a mutation. However, the calculation of the probability of finding substitution mutations at the same base position in the coding region of hprt indicates that there is no evidence for the presence of a hot spot for substitution mutations in the human hprt germ line. PMID- 2323783 TI - Germinal mosaicism in Crouzon syndrome. AB - Two sibs with classic Crouzon syndrome of the same mother but different fathers are presented as an example of germinal mosaicism in a known autosomal dominant disorder. The mother and both fathers were completely normal. PMID- 2323784 TI - The "polyclonal hyperimmunoglobulin G1(A1) syndrome" is a secondary phenomenon due to autoimmune disease. PMID- 2323785 TI - Bone marrow debacle. PMID- 2323786 TI - Coping through chemistry: a profile of the chemically dependent nurse. AB - Personal risk factors in becoming chemically dependent include attitudes, family history, and coping styles. Professional risk factors include drug accessibility and stress in the clinical environment. In conclusion, it is essential that nurses be personally aware of their risk potential for chemical dependency. Self awareness and knowledge can be powerful tools to use in interrupting the process of becoming chemically dependent. This, in turn, will safeguard the nurse herself, patients, and the profession. PMID- 2323787 TI - Hepatitis B vaccination programs. PMID- 2323788 TI - So you've been offered a management position. AB - As the demand for nurses opens management positions not previously available, nurses are increasingly facing the dilemma created by attractive job offers. Each nurse who is offered a management position needs to carefully assess her/his personal attributes as well as various factors about the position to determine the appropriateness of taking the position at the particular time. While few nurses manage the transition to management with ease, a poor decision can result in more than healthy growing pains. The deep trauma that may be inflicted by a painful experience in management may cause not only managerial burnout but even prompts some nurses to leave nursing. Premature timing in accepting a management position may not be in your best interest. On the other hand, a management position may offer you the challenge you have been waiting for and an opportunity to expand into a rewarding new nursing career. PMID- 2323789 TI - Advocating bicycle helmet use: a nursing issue. PMID- 2323790 TI - Blueprint for success on the NCLEX-RN. AB - When you graduate, you need to feel confident about your ability to pass the NCLEX-RN. Careful assessment of your performance in school can help you determine the amount and types of preparation you need for the examination. Spend your time on specific activities that fit your primary learning style. A systematic, organized approach to preparing for the NCLEX-RN is the most effective method for achieving success. PMID- 2323791 TI - Professional nursing: the impact of caring. PMID- 2323792 TI - Graduation day. PMID- 2323793 TI - Respect: a part of caring. PMID- 2323794 TI - Anencephalics as organ donors. PMID- 2323795 TI - Save those tax records. PMID- 2323796 TI - Role of electromyography in assessment of anorectal sensorimotor function. PMID- 2323797 TI - Effect of sublingual isosorbide dinitrate in portal hypertension. AB - Nitrates decrease portal pressure by decreasing portal venous inflow and resistance. We studied over 20 minutes the effect of 10 mg isosorbide dinitrate sublingual on intrasplenic pulp pressure, mean arterial pressure and heart rate, in 13 patients with cirrhotic or non-cirrhotic portal hypertension. The pulp pressure fell progressively over 20 minutes, from mean 43.6 +/- 2.4 (SEM) to 35.6 +/- 1.8 cm H2O (p less than 0.001). This was accompanied initially by a significant fall in mean arterial pressure (85.8 +/- 1.9 to 80.4 +/- 2.7 mmHg at 4 minutes; p less than 0.01) and rise in heart rate (92.5 +/- 5.0 to 102.6 +/- 5.9 per minute at 6 minutes; p less than 0.02), following which these parameters remained stable. One patient developed giddiness due to hypotension at 15 minutes. We conclude that sublingual isosorbide dinitrate decreases pulp pressure in cirrhotic and non-cirrhotic portal hypertensives, but this is initially accompanied by significant hemodynamic changes. PMID- 2323798 TI - Endoscopic removal of retained bile duct calculi via T-tube tract. AB - A simple and safe technique for removal of retained bile duct calculi using a flexible fibreoptic choledochoscope and rigid nephroscope via the T-tube tract has been described. The technique allowed removal of large impacted calculi under direct vision without damage to the bile duct. PMID- 2323799 TI - Liver in kala-azar. AB - Sixty patients with kala-azar were studied for liver involvement. Clinically none had any evidence of chronic liver disease. Biochemical evidence of hepatitis was seen in about 25% of cases while radiological and radionuclide studies failed to reveal portal hypertension and/or cirrhosis of liver in any of the patients. Histopathology of the liver in 18 patients failed to reveal any evidence of chronic liver disease or cirrhosis. It is suggested that portal hypertension and cirrhosis of liver probably do not occur as a consequence of kala-azar. PMID- 2323800 TI - Control of life-threatening hemorrhage in cecal tuberculosis by transcatheter embolisation. AB - Torrential hemorrhage is rare in tuberculous affection of the bowel. The traditional method of treatment has been immediate surgical intervention aimed at bowel resection. To our knowledge, this is the first report of successful control of such life-threatening hemorrhage by transcatheter embolisation. PMID- 2323801 TI - Tortuous aorta--a new cause for esophageal chest pain? AB - Three patients (average age 61 years) presenting with retrosternal pain were evaluated with barium studies of the upper gastrointestinal tract. In each case, the esophagus was significantly displaced by a tortuous aorta. All patients had sliding hiatal hernias; these hiatal hernias, and the esophagitis and disordered motility seen in our patients, could be a consequence of esophageal displacement by the tortuous aorta. Two patients were relieved symptomatically with antacids and metoclopramide. Thus, tortuosity of the thoracic aorta can cause esophageal chest pain. PMID- 2323802 TI - Indian childhood cirrhosis and kala-azar in a child. PMID- 2323803 TI - Nutritional management of portal systemic encephalopathy. PMID- 2323804 TI - Chemotactic competence of neutrophils from neonatal calves. Functional comparison with neutrophils from adult cattle. AB - Neonates demonstrate an increased susceptibility to infection. Defects in locomotory functions of newborn neutrophils may play a crucial role in this context. We therefore compared the migratory response of newborn (N-PMN) and adult (A-PMN) bovine neutrophils in a microwell filter assay. Stimulation with four different endotoxins (E. coli O128B:4 and O55B:5; S. abortus equi; S. typhimurium), with zymosan-activated plasma (ZAP) and with C5a induced dose dependent migration of A-PMNs and N-PMNs. Migration of unstimulated cells and of cells stimulated with diluted ZAP or C5a was higher (P less than 0.05) in N-PMNs. Migration of A- and N-PMNs towards C5a was inhibited (P less than 0.001) by preincubation with either a steroidal (122 microM flumethasone) or nonsteroidal (3.3 microM phenylbutazone) antiinflammatory drug. Migratory responses of N-PMNs were inhibited less by SAIDs than were responses of A-PMNs (P less than 0.05); indeed dexamethasone slightly enhanced N-PMN responses towards C5a, and 510 microM flunixin meglumine enhanced C5a-induced migration in both age groups. Endotoxins from E. coli O55:B4, S. abortus equi, and S. typhimurium induced a higher rate of migration (P less than 0.05) in N-PMNs. In contrast to the above findings, measurement of the maximal distance of migration by the leading-front method did not reveal age-related differences. Migration speed of PMNs was lower after stimulation with C5a than with ZAP, but could be restored partly by adding human vitamin D-binding protein (Gc-globulin). The demonstrated hyperirritability of bovine N-PMNs represents a major functional difference to neonatal neutrophils from other species, including man. It may additionally be related to altered PMN functions and neonatal disease susceptibility. PMID- 2323805 TI - Studies on inflammatory response induced by Ehrlich tumor in mice peritoneal cavity. AB - In the present study we investigated the inflammatory response induced by the inoculation of Ehrlich tumor cells (EAT) into the peritoneal cavity of mice. It was found that after inoculation of 10(3) EAT cells, the number of peritoneal leukocytes remained unchanged till the sixth day. Subsequently, the number of cells increased as a consequence of tumor growth. EAT cells did not induce influx of PMN leukocytes till six days after tumor implantation, but a significant influx was observed on the tenth day. Inoculation of the tumor cells did not induce production of H2O2 by peritoneal cells at any time examined and induced low levels of macrophage spreading only until the third day after tumor implantation but not later on. The levels of thromboxane in the peritoneal cavity were not affected by the presence of the tumor, whereas prostaglandin E2 levels were significantly increased at all times examined. The biological significance of these results on the evolution and escape of the tumor from host defense mechanisms is under investigation. PMID- 2323806 TI - Chemotactic response of human monocytes to pentapeptide analog derived from immunodeficiency virus protein gp 120. AB - The octapeptide sequence of peptide T is contained within the envelope of HIV and seems to mediate the viral binding to CD4 expressing cells, including monocytes. The biological activity of the alpha-aminobutyric acid pentapeptide derived from the C-terminal sequence of peptide T, in which the polar side chain of threonine in position 4 is substituted by a hydrophilic group, is measured by the monocyte chemotaxis assay. The chemotactic activity of human monocytes is assessed by determining the concentration at which the pentapeptide analog is maximally active and the effectiveness at that concentration, in comparison with peptide T and two shorter homologs, the pentapeptide and tetrapeptide. These experiments suggest that the synthetic analog is a potent chemotactic factor active at picomolar concentrations and that it competes with peptide T for the monocyte binding site. PMID- 2323808 TI - Deglycosylation of neutral and acidic human colonic mucin. AB - Human colonic mucin has been isolated from normal colonic mucosa by a phenol water extraction procedure and purified by Sepharose 2B column chromatography. The mucin was further purified by cesium bromide density gradient centrifugation. Sodium dodecyl sulfate-polyacrylamide gel (5%) electrophoresis of this material showed high-molecular-weight mucin component(s) at the top of the gel. Chemical analyses of this preparation indicated a typical mucin profile of amino acids and carbohydrates. Ion-exchange chromatography resulted in the separation of two major fractions, one being more acidic than the other. Chemical deglycosylation of the purified preparation at 20 degrees C for 3 1/2 showed loss of sialic acid, fucose, galactose, and N-acetylglucosamine, whereas traces of N acetylgalactosamine were still detected. High-pressure liquid chromatography of the deglycosylated material resulted in the purification of a major peptide, P1, with high levels of threonine, serine, and proline, resembling, in most respects, the profile of native mucin. The molecular weight of the peptide was determined to be approximately 97 kDa and serine was the single NH2 terminus. PMID- 2323807 TI - Calcium mobilization in C5a-stimulated adult and newborn bovine neutrophils. AB - Calcium (Ca2+) is an important second messenger central to many neutrophil (PMN) functional activities. Impaired Ca2+ mobilization in newborn PMNs following membrane perturbation could be one of the mechanisms underlying observed abnormalities in neonatal PMN function. To compare Ca2+ mobilization in bovine newborn and adult PMNs, cytosolic Ca2+ responses after stimulation with recombinant human C5a (rHC5a) were measured. PMNs from normal newborn calves (N = 6) and adult cows (N = 5) were loaded with fura-2/AM for 60 min at room temperature and the fluorescence changes monitored following stimulation with 0.1, 1, 10, or 50 nM rHC5a in Ca2(+)-containing buffer. Resting levels of Ca2+ in both newborn (54.6 +/- 1.9 nM) and adult (57.3 +/- 1.8 nM) bovine PMNs were comparable. After stimulation with rHC5a, a rapid rise of cytosolic Ca2+ was observed, which peaked within 20 sec and was followed by a sustained phase of elevated Ca2+ lasting up to 20 min. There were no significant differences (P greater than 0.05) in peak levels of cytosolic Ca2+ obtained by newborn and adult PMNs at 0.1, 10, and 50 nM rHC5a. At 1 nM rHC5a, newborn PMNs reached significantly (P less than 0.05) higher levels of cytosolic Ca2+ (217.9 +/- 21.7 nM) than did adult PMNs (158.7 +/- 7.9 nM). At 1 nM rHC5a, newborn PMNs also sustained higher levels of cytosolic Ca2+ for 3 min following the peak. At all concentrations of rHC5a tested, the time required to reach the peak and the duration of the peak were comparable in both populations. In the absence of extracellular Ca2+ (Ca2(+)-free buffer with 1 mM EGTA), resting levels of cytosolic Ca2+ were lower in both newborn (33.3 +/- 2.9 nM) and adult PMNs (27.9 +/- 2.4 nM) and the magnitude of the peak response to rHC5a was diminished at all concentrations of agonist. Additionally, in the absence of extracellular Ca2+, the return to basal cytosolic Ca2+ levels occurred rapidly and the sustained phase of increased cytosolic Ca2+ seen with rHC5a-stimulated PMNs in Ca2(+) containing buffer was virtually eliminated. These results indicate that bovine PMNs respond well to rHC5a, that stimulated newborn bovine PMNs can mobilize Ca2+ as efficiently as adult PMNs, and that the sustained cytosolic Ca2+ response to rHC5a in both age groups requires both release of Ca2+ from intracellular stores as well as influx of extracellular Ca2+. Such data suggest that observed functional deficits in newborn bovine PMNs are probably not related to improper mobilization of Ca2+ following stimulation. PMID- 2323809 TI - Con A-nonreactive human alpha 1-acid glycoprotein (AGP) is more effective in modulation of lymphocyte proliferation than Con A-reactive AGP serum variants. AB - Human alpha 1-acid glycoprotein (AGP) has been shown to modulate various cellular and humoral immune reactions in vitro. Using glycosidase-modified derivatives of AGP, the importance of its carbohydrate moiety with regard to these effects has been noted. In normal serum, three molecular AGP forms interacting differently with concanavalin A (Con A) are present. The ratio of these forms is often changed during various physiopathological conditions. In this study, we could show that differences exist between the three AGP forms with regard to their immunomodulatory effectiveness. At physiological concentrations, the Con A nonreactive variant AGP-A induced a stronger inhibition of the anti-CD3 stimulated lymphocyte proliferation than the other forms. Interestingly, AGP-A was also found to be responsible for the stimulation of lymphocyte proliferation induced by low AGP concentrations in vitro. Both immunomodulatory effects of AGP were abrogated by desialylation of the glycoprotein. These results support an immunomodulatory role of AGP in conditions characterized by a changed ratio of the differently glycosylated AGP forms. PMID- 2323810 TI - Compartmental heterogeneity of soluble phospholipases A. AB - Multiple forms of soluble phospholipase A2 (PLA2) are known to coexist in venoms of individual reptilian species. While similar observations in several mammalian species suggest that this is a common phenomenon, the functional implications are not yet understood. In attempting to devise therapeutic strategies for treatment of inflammatory disorders by inhibition of PLA2, it is imperative to define the various PLA2 species in the relevant compartments. Herein, we report the presence of three PLA2 isotypes in rheumatoid arthritis serum, one pancreatic and two nonpancreatic phospholipases A2. The pancreatic and one of the nonpancreatic forms were optimally active in 7 mM calcium at pH 7.5. The other nonpancreatic form was calcium-independent and optimally active at pH 7.0. Only the calcium dependent nonpancreatic form was observed in rheumatoid synovial fluid. Of the three serum isotypes, only the calcium-dependent nonpancreatic form correlated with markers of disease activity, such as the joint count and Landsbury index. Therefore, not all soluble or circulating phospholipases A2 are relevant to inflammatory processes. Selective inhibition of the proinflammatory form of PLA2 may prove to have some therapeutic benefit while minimizing the possible adverse effects of this form of intervention. PMID- 2323811 TI - Desensitization of rabbit skin by repeated exposure to UV-visible light of sites injected with Rose Bengal. AB - We have shown in a previous paper that irradiation of rabbit skin sites injected with Rose Bengal (RB) produces immediate increase in vascular permeability and accumulation of PMNs. Studies on the development of temporary tolerance and the biological parameters related to the development of such tolerant state by repeated exposure to light of RB-injected sites are reported here. The increase in VP and PMN migration induced by RB (10 nmol) are of an immediate nature, i.e., occur within the first 3 h of irradiation, and the reaction subsides gradually after 24 h. When such moderate insult is repeated, the skin becomes tolerant to subsequent exposure to light in the presence of RB. This tolerant state is temporary, i.e., the desensitized sites are fully recovered in 72 h. The loss of responsiveness of RB-injected sites previously exposed to light was not due to diffusion of the injected dye from the sites since reinjected sites also showed reduced response and the sites injected three days before but not irradiated showed normal response. The sites that were made tolerant to RB-induced phototoxic reactions, when injected with compound 48/80, an agent known to degranulate mast cells, did not show an increase in VP. This suggests that either the mast cells were depleted from the sites or the mast cells in the sites were rendered refractory by previous exposure to light. It was also found that the sites made tolerant to RB plus light were unresponsive to exogenously injected histamine. The sites tolerant to RB plus light when injected with zymosan activated serum (ZAS) did not stimulate the migration of PMNs. This loss of chemotactic response to ZAS may have relevance to photodamage of vascular endothelium. These observations are discussed in relation to the development of the tolerant state by repeated exposures to subthreshold doses of light in solar urticaria. PMID- 2323812 TI - T-cell hybridomas reveal two distinct mechanisms of antileishmanial defense. AB - Using lymph node lymphocytes of Leishmania major-infected mice, we constructed and cloned two T-cell hybridomas that could activate macrophages to exert antileishmanial defense in vitro. One clone, 1D5, produced lymphokines (including gamma interferon) that induced these effects. Production of the macrophage activating lymphokines and the protective effect of 1D5 were suppressed by the addition of cyclosporine A to cultures. The other clone, 1B6, produced no detectable macrophage-activating lymphokines, and its protective ability was not suppressed by cyclosporine A. Granulocyte-macrophage colony-stimulating factor (a lymphokine also known to induce antileishmanial effects in macrophages) was not detectable in culture supernatants of either clone. Furthermore, neither clone was cytotoxic to infected macrophages. Antileishmanial defense induced by 1B6 was genetically restricted; that is, infected macrophages and hybridoma cells had to be syngeneic for an antileishmanial effect to occur. In contrast, such restriction was not a property of clone 1D5, a clone that was responsive to alloantigens as well as leishmanial antigens. When incubated at a temperature (34 degrees C) at which lymphokines are relatively ineffective for antileishmanial defense, 1B6 but not 1D5 retained its antileishmanial properties. These observations provide clear evidence for the existence of two distinct mechanisms of macrophage activation: one that is lymphokine dependent, and one that is apparently lymphokine independent. The expression of these two mechanisms by cloned cells strongly suggests that they are properties of different T-cell subpopulations, extending our prior conclusions based on studies of heterogeneous T-cell populations. We hypothesize that the latter macrophage activation process involves a cell contact-dependent mechanism which might involve the interaction of a lymphocyte membrane-associated macrophage-activating factor (such as tumor necrosis factor) with its receptor on the macrophage, resulting in activation of antileishmanial effects but not host cell cytotoxicity. PMID- 2323813 TI - Correlation between the presence of sequences homologous to the vir region of Salmonella dublin plasmid pSDL2 and the virulence of twenty-two Salmonella serotypes in mice. AB - Large plasmids encoding important virulence properties have been found in several Salmonella serotypes. We have studied the relationship between the presence of a highly conserved 4-kilobase (kb) EcoRI fragment from the plasmid virulence region and pathogenicity for mice of 53 isolates representing 22 serotypes of Salmonella. Only strains possessing the homologous 4-kb region were virulent for mice. In addition, we transferred the virulence plasmid from S. dublin into nine different serotypes, including S. typhi and S. paratyphi A, that lack a native virulence plasmid. Only S. heidelberg and S. newport were rendered mouse virulent by the introduction of the S. dublin plasmid. This study demonstrates that plasmid-mediated virulence sequences are required for Salmonella virulence in mice, but many strains, including the agents of human typhoid fever, also lack chromosomal genes necessary to produce lethal systemic disease in mice. Since all the major Salmonella strains that are host-adapted to animals carry virulence plasmids, it appears that these plasmids are important in mediating systemic infection in animals and may contribute to septicemic, nontyphoid salmonellosis in humans. PMID- 2323814 TI - Synthesis and secretion of Bordetella pertussis adenylate cyclase as a 200 kilodalton protein. AB - Bordetella pertussis, the etiological agent of whooping cough, synthesizes a calmodulin-sensitive adenylate cyclase that is suspected to play a major role in the virulence of this bacterium. We show that adenylate cyclase synthesized as a 200-kilodalton protein is the product of the cyaA gene and that various virulent Bordetella species secrete this high-molecular-weight polypeptide without apparent proteolytic processing. When submitted to trypsin digestion, the 200 kilodalton protein was converted to a stable 45- to 50-kilodalton species. This corresponds to the size of the enzyme previously purified from a culture supernatant. The molecular heterogeneity reported for the various identified forms of adenylate cyclase could therefore result in part from proteolytic degradation or molecular aggregation of the major 200-kilodalton form of the enzyme. PMID- 2323815 TI - Antibody responses to Toxoplasma gondii in sera, intestinal secretions, and milk from orally infected mice and characterization of target antigens. AB - Toxoplasma gondii-specific antibody responses in serum, intestinal secretions, and milk were identified with an enzyme-linked immunosorbent assay following a single oral infection of mice with strain 76K cysts of T. gondii. Immunoglobulin A (IgA) production began during week 2 of infection in serum and milk and during week 3 of infection in intestinal secretions and persisted in all three throughout the experiment (17 weeks). IgG but not IgM antibodies were detected in intestinal secretions later in the infection. Serum and milk IgG and IgM production began at the same time after infection as did the IgA response. In Western blotting (immunoblotting), intestinal IgA antibodies were shown to react with antigens comigrating with the T. gondii proteins p22, p23, p30, and p43, the 28-kilodalton antigen, and the 55- and 60-kilodalton rhoptry proteins, as recognized by specific monoclonal antibodies. Milk IgA antibodies reacted with antigens comigrating with p30 and p43. Most of the antigens recognized by IgA antibodies were also detected by IgG antibodies. IgA antibodies from all three biological samples detected the same major T. gondii antigens; thus, there was apparently no specific antibody production unique to one locality. PMID- 2323816 TI - Mycoplasma fermentans-derived high-molecular-weight material induces interleukin 6 release in cultures of murine macrophages and human monocytes. AB - A Mycoplasma fermentans-derived high-molecular-weight material (MDHM) is described which causes differentiation of concanavalin A-stimulated CBA/J or C57BL/6 mouse thymocytes to cytolytic effector T cells (CTLs). The effect of MDHM was inhibited by addition of monoclonal anti-interleukin-6 (IL-6) antibody. It could also be abolished after removal of adherent cells. However, adherent cell depleted thymocytes could still form CTLs after addition of IL-6. The action of MDHM could thus be explained by the capacity of MDHM to stimulate IL-6 release from adherent cells. MDHM was active on macrophages from CBA/J and C3H/HeJ endotoxin nonresponder mice and was also capable of stimulating IL-6 release from human monocytes. On gel chromatography, MDHM had an apparent molecular size of 1.5 x 10(6) daltons. Treatment with RNase and DNase had no effect on either size or biological activity. Proteinase K did not abolish activity but reduced the apparent molecular size of MDHM. MDHM production by M. fermentans required either coculture with eucaryotic cell lines in RPMI 1640 medium with fetal calf serum or addition of eucaryotic cell sonic extracts to this medium. The biological activity of MDHM is not identical to that of a mitogen for murine spleen cells derived from M. arthritidis; MDHM caused only slight proliferation in this system compared with the mitogen from M. arthritidis, and the latter did not elicit IL-6 release from macrophages. The results are discussed in relation to mycoplasmas as putative etiological agents for rheumatoid arthritis, since high IL-6 titers were reported for synovial fluid from patients with this disease. PMID- 2323817 TI - Cloning and expression of the gene encoding the fructose-1,6-diphosphate dependent L-(+)-lactate dehydrogenase of Streptococcus mutans. AB - The fructose-1,6-diphosphate-dependent lactate dehydrogenase from Streptococcus mutans JH1000 was purified by a modification of published methods. The sequence of 27 amino-terminal amino acids was determined, which allowed us to construct a 17-base DNA probe that had 32-fold degeneracy. The probe was used to screen a genomic library in pBR322. Of 18 reactive clones, 1 was found that expressed lactate dehydrogenase (LDH) activity identical to that of S. mutans with regard to dependence on fructose-1,6-diphosphate, thermal inactivation profile, and inhibition by sodium oxamate. Extracts of this clone possessed a protein band that comigrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with purified LDH from JH1000. Compared with controls, the clone was shown to produce elevated amounts of L-(+)-lactic acid during growth in the presence of glucose, thereby indicating that the activity was expressed in vivo. This result was substantiated by demonstrating that the activity could complement a mutation in the fermentative D-(-)-LDH of Escherichia coli. Subcloning showed that the S. mutans LDH subunit is encoded by a 1.2-kilobase gene. Our ability to clone this gene is expected to have great practical significance in the construction of an effector strain for use in the replacement therapy of dental caries. PMID- 2323818 TI - Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough. AB - the introduction of two amino acid substitutions within the enzymatically active subunit S1 of pertussis toxin (PT) abolishes its ADP-ribosyltransferase activity and toxicity on CHO cells (Pizza et al., Science 246:497-500, 1989). These genetically inactivated molecules are also devoid of other in vivo adverse reactions typical of PT, such as induction of leukocytosis, potentiation of anaphylaxis, stimulation of insulin secretion, and histamine sensitivity. However, the mutant PT molecules are indistinguishable from wild-type PT in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and maintain all the physical and chemical properties of PT, including affinity for toxin-neutralizing poly- and monoclonal antibodies. Either alone or stabilized with formaldehyde, PT mutants are able to induce high levels of neutralizing antibodies and to protect mice in a dose-dependent fashion against intracerebral challenge with virulent B. pertussis. These results clearly show that these genetically inactivated PT molecules are nontoxic but still immunogenic and justify their development as a component of a new, safer acellular vaccine against whooping cough. PMID- 2323819 TI - Antiphagocytic effect of the capsule of Staphylococcus simulans. AB - An encapsulated strain of Staphylococcus simulans was observed to be more resistant to phagocytosis by human granulocytes than was a nonencapsulated strain. Phagocytosis of the encapsulated strain was enhanced by antisera to S. simulans, but opsonic activity of antisera was removed by absorption with S. simulans capsular material. The encapsulated strain of S. simulans was also more invasive than the nonencapsulated S. simulans in vivo. More encapsulated than nonencapsulated S. simulans were found in heart blood when equal numbers of organisms were injected intraperitoneally into mice. Invasion of the bloodstreams of mice by encapsulated S. simulans was prevented by passive immunization (rabbit antiserum). Thus, the capsule of S. simulans inhibited phagocytosis in vitro and contributed to virulence in vivo. PMID- 2323820 TI - Suppression of tumor necrosis factor alpha production by a human immunoglobulin preparation for intravenous use. AB - We investigated the effect of a pH 4-treated human immunoglobulin preparation for intravenous use (pH4-G) on the production of tumor necrosis factor alpha (TNF alpha) in vivo. The level of TNF-alpha in the sera of rabbits receiving pH4-G before lipopolysaccharide (LPS) injection was lower than that in rabbits receiving only LPS. Similarly, the in vitro production of TNF-alpha was suppressed by pH4-G. Rabbit peritoneal exudate cells stimulated with LPS in the presence of pH4-G produced less TNF-alpha than did those stimulated only with LPS. pH4-G, however, had no effect on various TNF-alpha activities, such as cytotoxicity against tumorigenic murine fibroblasts (L929 cells), induction of interleukin-1 production, or fever induction. These results indicate that pH4-G suppresses TNF-alpha production without affecting TNF-alpha activities. A suppressive effect on the expression of TNF-alpha mRNA was also observed. PMID- 2323821 TI - Specific labeling of cysteine proteinases in pathogenic and nonpathogenic Entamoeba histolytica. AB - Growth of Entamoeba histolytica trophozoites was inhibited by 50% at low concentrations (2.0 micrograms/ml) of the diazopeptidyl inhibitor benzyloxycarbonyl-leucyl-L-tyrosyldiazomethane (Z-L-Leu-L-Tyr-CHN2). Iodination of the tyrosine residue lowered the growth inhibitory efficacy of the diazopeptidyl inhibitor (50% inhibition, approximately 10 micrograms/ml). However, even at this concentration, practically all of the cysteine proteinase activity of the cells was irreversibly inactivated as shown by fluorescence microscopy with the dipeptide substrate L-Arg-L-Arg-4-methoxy-beta-napthylamide or colorimetrically with azocasein as the substrate. Growth of trophozoites of E. histolytica from various strains, including both pathogenic and nonpathogenic zymodemes, was similarly inhibited. The concentration of inhibitor required to inactivate the proteinase activity of nonpathogenic cells was lower. Lysates from trophozoites grown in the presence of sublethal concentrations of 125I-labeled protease inhibitor (10 micrograms/ml) showed as many as eight radioactive bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (molecular sizes, 73, 68, 56, 40, 39, 35, 29, and 27 kilodaltons). Two of these bands (molecular sizes, 29 and 27 kilodaltons) could be seen in gels of the cytoplasmic fraction, whereas the high-molecular-size bands were mostly associated with the membrane fraction. The radioactive bands in pathogenic and nonpathogenic strains were very similar with only minor differences. The results obtained show that E. histolytica cells, irrespective of their pathogenicity, possess a number of cysteine proteinases of similar molecular sizes which are vital for cell growth. PMID- 2323822 TI - Production, characterization, and species specificity of monoclonal antibodies to Mycobacterium avium complex protein antigens. AB - The incidence of Mycobacterium avium-Mycobacterium intracellulare complex infections has increased in recent years primarily because a significant proportion of acquired immunodeficiency syndrome patients develop disseminated M. avium complex disease. In an effort to develop new tools to study these infections, we have produced eight monoclonal antibodies directed against M. avium. Western blot (immunoblot) specificity analysis and protease sensitivity assays indicate that four of these antibodies recognize M. avium-specific protein epitopes and two react with M. avium complex-specific peptide determinants. These monoclonal antibodies may be useful clinically in the diagnosis of M. avium complex disease and in the laboratory for isolation and characterization of native and recombinant M. avium complex antigens. PMID- 2323823 TI - Effects of exogenous agents on the action of Bordetella parapertussis heat-labile toxin on guinea pig skin. AB - Injection of sonic extracts of Bordetella parapertussis into the shaved backs of guinea pigs produced hemorrhagic necrosis, which previously has been attributed to the action of heat-labile toxin. As heat-labile toxin was purified from this crude mixture, its ability to induce hemorrhagic lesions decreased significantly. However, ischemic lesions were apparent after injection of the purified toxin. These lesions, while not hemorrhagic in nature, were marked by erythema surrounded by a region in which the ischemia was apparent. Exogenous agents were found to alter the nature of the skin lesion induced by heat-labile toxin. The lipid A portion of endotoxin in combination with heat-labile toxin caused hemorrhagic lesions surrounded by a ring of ischemia, whereas bovine serum albumin increased the area of erythema. While the nature of lesions induced by heat-labile toxin was affected by exogenous agents, the diameter of ischemia produced by the toxin was found to be independent of the presence of these agents and was linear with toxin dose. These results indicate that induction of hemorrhagic necrosis may not be a reliable indicator of heat-labile toxin activity. Instead, measurement of the ischemic lesion produced by heat-labile toxin may be a useful assay for the toxin. PMID- 2323825 TI - Amino acid sequence of a deltalike toxin from Staphylococcus epidermidis. AB - A deltalike toxin produced by a clinical isolate of Staphylococcus epidermidis was purified, and the amino acid sequence was determined. The toxin molecule consisted of 25 amino acid residues and shared a high degree of molecular homology with delta toxin purified from a Staphylococcus aureus human isolate. PMID- 2323824 TI - Cross-reactivity and sequence homology between the 65-kilodalton mycobacterial heat shock protein and human lactoferrin, transferrin, and DR beta subsets of major histocompatibility complex class II molecules. AB - Immunogold ultracytochemistry and Western immunoblotting showed that polyclonal antibodies against human lactoferrin bind to the highly immunogenic 65-kilodalton (kDa) heat shock protein of mycobacteria. The fast-growing mycobacterial species Mycobacterium smegmatis showed a higher density of these receptors for antilactoferrin sera than the slow-growing M. avium. Polyclonal antibodies against mycobacteria (M. bovis BCG) recognized human lactoferrin. Comparison of the amino acid sequence of lactoferrin with that of the 65-kDa protein of M. tuberculosis revealed seven instances of four amino acid sequence homology between the microbial and the human iron-binding protein. Four of these tetrapeptide sequences were also shared with the human transferrin molecule. The shared amino acid sequence KDLL was also present in the DR1, DR3, and DR4 subsets of the DR beta subregion of major histocompatibility complex (MHC) class II molecules. The molecular mimicry between the 65-kDa mycobacterial protein and the human proteins (lactoferrin, transferrin, and MHC class II molecules) offers a molecular setting for mycobacteria-associated, T-cell-dependent autoimmune disease, namely, for rheumatoid arthritis. PMID- 2323826 TI - Use of DBA/2N mice in models of systemic candidiasis and pulmonary and systemic aspergillosis. AB - Mouse models of systemic candidiasis and pulmonary and systemic aspergillosis were established by using DBA/2N mice, which are known to be deficient in the C5 component of complement. In experiments comparing lethality in the respective models in DBA/2N versus outbred CFW mice, results showed that the 50% lethal dose values for the DBA/2N mice were 10- to 1,000-fold lower than those for the outbred mice, depending on the experiment. Additionally, onset of death was somewhat delayed for the DBA/2N mice. In the case of the pulmonary aspergillosis model, administration of cortisone acetate was necessary to ensure lethality after intranasal infection, but only a single dose was necessary. PMID- 2323827 TI - Evidence that a low-affinity sucrose phosphotransferase activity in Streptococcus mutans GS-5 is a high-affinity trehalose uptake system. AB - High-affinity sucrose uptake in the oral pathogen Streptococcus mutans is mediated by the phosphoenolpyruvate-dependent phosphotransferase system. In this report, we provide evidence that a lower-affinity sucrose phosphotransferase system in S. mutans GS-5, previously described by others, is in fact a high affinity trehalose uptake system that also recognizes sucrose as a substrate. PMID- 2323828 TI - Diminished immunogenicity of a recombination-deficient derivative of Vibrio cholerae vaccine strain CVD103. AB - To address potential concerns over the release of genetically engineered live bacterial vaccines, we constructed a recombination-deficient derivative of the Vibrio cholerae O1 vaccine strain CVD103 (CVD103RM). Oral immunization of adult volunteers with CVD103RM showed that the recA mutation significantly diminished colonization ability and immunogenicity of the vaccine strain. PMID- 2323829 TI - Influence of Pasteurella haemolytica A1 crude leukotoxin on bovine neutrophil chemiluminescence. AB - Pasteurella haemolytica A1 crude leukotoxin (25%, vol/vol) rapidly diminished the bovine neutrophil chemiluminescence response to opsonized zymosan. This inhibition was neither prevented nor reversed by 75 mM sucrose. Dilute leukotoxin did not directly stimulate neutrophil chemiluminescence nor did it alter the chemiluminescence response of the neutrophils to opsonized zymosan. PMID- 2323830 TI - Occupational chronic exposure to organic solvents. XIII. Glycolether exposure during the production of varnishes. AB - Seventeen persons (2 women and 15 men), who were exposed to glycolethers in a varnish production plant, were examined according to their external and internal solvent exposure. The workers in the production plant (n = 12) were exposed to average concentrations of ethoxyethanol, ethoxyethyl acetate, butoxyethanol, 1 methoxypropanol-2, 2-methoxypropyl-1-acetate and xylene of 2.8; 2.7; 1.1; 7.0; 2.8 and 1.7 ppm. In the air of the store (n = 3) and in the laboratory (n = 2) only minor concentrations of xylene respectively xylene and ethoxyethyl acetate could be measured. Internal exposure was estimated by measuring butoxyethanol (BE) in blood as well as ethoxyacetic acid (EAA) and butoxyacetic acid (BAA) in urine samples. Urine samples were taken pre- and post-shift. As expected, the highest values were found in the varnish production. The average post shift concentrations of BE, EAA and BAA were 121.3 micrograms/l; 167.8 and 10.5 mg/l. The relatively high concentrations of EAA and BAA in pre-shift samples can be explained by the long half-lives of these metabolites. According to our findings most of the glycolethers were taken up through the skin. Comparing our results with those reported in the literature we think that a future tolerable limit value for the concentration of ethoxyacetic acid in urine should be in the order of 100 to 200 mg/l. PMID- 2323831 TI - Neuropsychiatric disorders among solvent-exposed workers. First results from a Dutch case-control study. AB - This case-control study was undertaken to determine whether exposure to organic solvents, as experienced by Dutch painters, causes an increased risk of disability due to neuropsychiatric disorders. Cases and controls were selected from the Dutch Painters' and Construction Workers' Organizations. Cases were defined as male persons receiving disability benefits due to neuropsychiatric disorders. The controls consisted of a random sample of 1000 male persons from the total study population. Cases (n = 252) and controls (n = 822) participated in our study by returning the completed questionnaires. The questionnaire was used to collect information about occupational history and the presence of potentially confounding factors. The adjusted Odds Ratio for the total group of neuropsychiatric disorders did not reach a statistically significant level (OR = 1.17; P less than 0.30). Although a stronger association was suggested between "neuroses" (ICD 300) and exposure to organic solvents (OR = 2.30; P less than 0.05), there are indications that this relationship is merely the result of classification bias. The results of this study do not confirm, but also do not completely exclude, that Dutch painters are at increased risk of being prematurely disabled due to neuropsychiatric disorders. PMID- 2323832 TI - Assessment of changes in eye redness by a photographic method and the relation to sensory eye irritation. AB - The purpose of the present study was to evaluate the relation between photographically assessed changes in eye redness and sensory eye irritation in 17 patients suffering from hayfever, provoked by increasing doses of birch pollen in the eye. Pre- and post-exposure diapositives were compared in a randomized and double blind design by a panel of five members. By evaluating the photographs we found a high reproducibility between panel members and for repeated evaluation by the individual panel member. Furthermore, we found that the photographic method was more sensitive for measurements of changes in eye redness than the observations normally performed during such conjunctival provocation tests. The correlations of the objective findings with the symptoms reported were good at high pollen doses, but at lower doses of birch pollen (about half the effective dose) a decreased eye redness was observed. We found that sensory irritation (often expressed as dryness) measured simultaneously by questionnaires, in general occurred before any increased eye redness. The study indicates that photographic measurement of eye redness is reproducible, sensitive, unbiased and therefore a useful tool in environmental studies. Furthermore we demonstrated that the relation between eye redness and eye irritation is interestingly biphasic and may need further clarification. PMID- 2323833 TI - Health effects of exposure to endotoxins and organic dust in poultry slaughter house workers. AB - Twenty-three dust-exposed shacklers in the hanging departments of four poultry slaughter-house plants were examined immediately before work on a Monday morning with a standardized interview, pulmonary function tests (VC and FEV1), and blood sampling for analysis of complement factors. The examinations were repeated immediately after work the same day. Further, the individual breathing zone levels of both total dust and endotoxins were monitored during the whole work shift. Moreover, spot samples of airborne bacteria and fungi were collected. The mean level of total dust was 6.3 mg/m3 (range 0.4-15.3 mg/m3) and of endotoxins 0.40 micrograms/m3 (range 0.02-1.50 micrograms/m3). Total levels of 4 x 10(5)-4 x 10(6) cfu/m3 of airborne bacteria, mainly coagulase-negative staphylococcal strains, but only 500-4000 cfu/m3 of fungi were found in the hanging departments. An over-shift increase in respiratory symptoms was found, but none of the workers had experienced any symptoms indicating extrinsic allergic alveolitis (EAA) or organic dust toxic syndrome (ODTS). Further, mean over-shift decreases of VC (3.1%) and FEV1 (4.1%) were found, indicating a harmful effect on the bronchi. There were, however, no associations between these over-shift decreases and the individual time-weighted average breathing zone levels of either total dust or of endotoxins. No over-shift change in serum complement factors was observed. PMID- 2323834 TI - Urinary excretion of unmetabolized acetone as an indicator of occupational exposure to acetone. AB - Acetone concentrations in urine samples from 28 workers exposed to acetone in a fiber-reinforced plastics factory were determined by directly injecting urine supernate into a gaschromatograph with FID detectors. Acetone concentrations in the urine from ten nonexposed subjects were also determined. The 8-h time weighted exposure intensity of individual workers was monitored by means of diffusive sampling. Acetone concentration in urine and acetone concentration in the breathing zone showed a linear correlation to each other. The study results indicate that the correlation coefficient is high enough to enable use of the urinary level of acetone as an indicator of occupational exposure to acetone. PMID- 2323835 TI - Sister chromatid exchanges in peripheral lymphocytes of workers exposed to benzene, trichloroethylene, or tetrachloroethylene, with reference to smoking habits. AB - The frequencies of sister chromatid exchanges (SCE) were studied in peripheral lymphocytes from four groups of solvent workers, i.e. 36 nonsmoking women exposed to benzene at about 50 ppm on the average, 38 men and women (male smokers and nonsmokers, and female nonsmokers) exposed to trichloroethylene (TRI) at 7 ppm, 27 men and women (both smokers and non-smokers) with tetrachloroethylene (TETRA) exposure, and 19 workers (both smokers and nonsmokers in men, and nonsmokers in women) exposed to a mixture of TRI (at 8 ppm) and TETRA (at 17 ppm) (TRI + TETRA). The results were compared with the findings in control subjects matched by age, sex, smoking habits and place of residence. No significant increase in SCE frequencies was observed in association with exposure to benzene, TRI, TETRA or TRI + TETRA. The SCE frequency was, however, significantly higher in the TRI-, TETRA- or TRI + TETRA-exposed smoking men than in the concurrent nonsmoking controls of the same sex. Possible synergism between solvent exposure and smoking is discussed. PMID- 2323836 TI - Responses of sympathetic nervous system to cold exposure in vibration syndrome subjects and age-matched healthy controls. AB - Plasma norepinephrine and epinephrine in vibration syndrome subjects and age matched healthy controls were measured for the purpose of estimating the responsibility of the sympathetic nervous system to cold exposure. In preliminary experiment, it was confirmed that cold air exposure of the whole body was more suitable than one-hand immersion in cold water. In the main experiment, 195 subjects were examined. Sixty-five subjects had vibration syndrome with vibration induced white finger (VWF + group) and 65 subjects had vibration syndrome without VWF (VWF- group) and 65 controls had no symptoms (control group). In the three groups, plasma norepinephrine levels increased during cold air exposure of whole body at 7 degrees +/- 1.5 degrees C. Blood pressure increased and skin temperature decreased during cold exposure. Percent increase of norepinephrine in the VWF+ group was the highest while that in VWF- group followed and that in the control group was the lowest. This whole-body response of the sympathetic nervous system to cold conditions reflected the VWF which are characteristic symptoms of vibration syndrome. Excluding the effects of shivering and a cold feeling under cold conditions, it was confirmed that the sympathetic nervous system in vibration syndrome is activated more than in the controls. These results suggest that vibration exposure to hand and arm affects the sympathetic nervous system. PMID- 2323837 TI - N-myc gene is amplified in alveolar rhabdomyosarcomas (RMS) but not in embryonal RMS. AB - DNA from 13 (6 alveolar and 7 embryonal) childhood rhabdomyosarcomas (RMS) was examined to determine the incidence and prognostic relevance of N- and c-myc genes. Southern analysis showed 5- to 20-fold amplification of N-myc gene in 4 of 6 alveolar but in none of 7 embryonal RMS (p less than 0.04; Fisher's exact test). The number of children who died with multiple- and single-copy N-myc gene was 4/4 and 5/9 respectively (p greater than 0.05; Chi-squared test). There was no statistically significant correlation between N-myc amplification and age, gender, site, stage or survival time. There was no amplification or gross rearrangement of c-myc in any of the 13 RMS. PMID- 2323838 TI - Tumor progression by DNA flow cytometry in human colorectal cancer. AB - We wished to better understand the role of aneuploidy during the progression of human colorectal cancer. Fresh or frozen multiple samples from 221 human colorectal adenomas, 93 carcinomas, and corresponding control mucosa were investigated using high-resolution DNA flow cytometry. A total number of 164 DNA abnormal clones were observed and characterized by a quantitative index of DNA aneuploidy (DI). In precancerous lesions the vast majority of DNA abnormal clones (almost 3/4 in adenomas with mild to moderate dysplasia) was hypo- and hyper diploid with DI values from 0.8 to 1.2 (near-diploidy). In moderately to poorly differentiated carcinomas the vast majority of abnormal clones was near-triploid and hypotetraploid with DI values from 1.4 to 1.8 (near hypertriploidy) and only 12% were near-diploid. Adenomas with foci of carcinomas, a group of special interest since they represent a link in colorectal tumor progression, had median triploid DNA content. In addition to an increase in DI values, the carcinomas had a clear increase in the proportion of cells actively synthesizing DNA (S-phase fraction). These results are interpreted as evidence for a ploidy-evolution model according to which near-diploid clones in adenomas at early stages of dysplasia would derive from abnormal mitotic cells that divide their DNA unequally between two daughter cells. Tetrapolidization of these near-diploid cells and successive DNA loss would then lead in later stages of tumor progression to near hypertriploid clones characterized by a balance of chromosomes bearing growth promoting and growth-suppressing genes confering a selective proliferative advantage. PMID- 2323839 TI - Expression of the mdr3 gene in prolymphocytic leukemia: association with cyclosporin-A-induced increase in drug accumulation. AB - Typical multidrug resistance in human and animal cell lines is caused by overactivity of an unidirectional transmembrane drug efflux pump, encoded by the MDR genes, called mdr genes in mice and humans and pgp genes in hamsters. In humans, two mdr genes, mdr1 and mdr3, with approximately 80% nucleotide homology, have been identified. There is increasing evidence that overexpression of the mdr1 gene plays a role in resistance to anticancer agents in specific tumor types. However, currently no data are available on a possible role for mdr3 in drug resistance. Here we report high levels of expression of mdr3 gene sequences in leukemic cells from 6 out of 6 patients with prolymphocytic leukemia (PLL). No mdr1 expression was detected in 5 out of 6 of these samples, whereas a low level of mdr1 expression was found in a sample from one PLL patient in the course of transformation to non-Hodgkin's lymphoma. Except for this patient, all other PLL cases studied had not received prior chemotherapy. In vitro drug uptake studies showed that daunorubicin accumulation in PLL cells was increased by cyclosporin A. Since cyclosporin A is an inhibitor of the mdr1-encoded P-glycoprotein drug pump, these data suggest that in PLL cells mdr3 also codes for a drug efflux pump. Our findings could partly explain the primary refractoriness of PLL to chemotherapy. PMID- 2323840 TI - Malignant lymphoma of the central nervous system in Japan: histologic and immunohistologic studies. AB - Ninety-seven Japanese patients with so-called primary non-Hodgkin's lymphoma of the central nervous system (CNS-NHL), unrelated to the acquired immunodeficiency syndrome (AIDS) or organ transplantation, were reviewed. The patients' ages ranged from 1 to 87 years (median: 58 years) with a male to female ratio of 1.77:1. The most frequent past histories were acute appendicitis (appendectomy), head injury, uveitis or iritis, and gastritis or gastric ulcer. These patients presented with symptoms suggesting an expanding intracranial lesion with no signs of extracranial lymphomatous disease. Combined computed tomographic scans, angiography, and findings at surgery or autopsy showed that the cerebrum was the commonest site of involvement, 87% of all cases, with the frontal to temporal region being the most commonly involved. Histologically, the diffuse large-cell type was most frequent and 26% of lymphomas were of high-grade malignancy as defined by the Working Formulation. The reported frequency of high-grade CNS-NHLs in AIDS patients in the United States is much higher (over 60%). Immunohistochemistry on paraffin-embedded sections revealed a B-cell nature of the present series of tumors. In 16% of the cases, large numbers of small lymphoid cells with a positive reaction predominantly for anti-T lymphocyte antibodies surrounded the tumors or aggregated around the capillaries. The tumors which were infiltrated by small lymphoid cells showed more favorable prognosis than those which were not, suggesting a host reaction to tumor growth in these patients. PMID- 2323841 TI - The distribution of non-Burkitt, non-Hodgkin's lymphomas in Uganda in relation to malarial endemicity. AB - Biopsies of malignant lymphomas collected from all districts of Uganda, filed in the Kampala Cancer Registry for the 8-year period 1966-1973, were reviewed. This review confirmed a relatively low frequency of follicle-centre-cell lymphomas with a follicular growth pattern and the geographical co-distribution between malaria and Burkitt's lymphoma (BL). It also showed a similar, though less marked, association between non-Burkitt, non-Hodgkin's lymphoma (NBNHL) and malarial endemicity, and a correlation in the regional incidence between BL and NBNHL. In both comparisons, these associations were strong for high-grade lymphomas and weak for low-grade neoplasms. BL and other NHL may therefore share, to a varying degree, some common pathogenesis. The excess in frequency of NBNHL of high-grade malignancy in malarial endemic areas appears to be in contrast to Western countries where most non-Hodgkin's lymphomas are of low-grade malignancy. PMID- 2323842 TI - Risk factors for male breast cancer: a Franco-Swiss case-control study. AB - In order to evaluate risk factors in male breast cancer, a case-control study of 91 histologically diagnosed cases and 255 cancer controls, matched for age and year of diagnosis, was conducted in Villejuif (France) and Geneva (Switzerland). Factors studied included marital history, occupational exposure, associated diseases, family history of breast cancer, history of radiation exposure and drugs which increase or are suspected of increasing prolactin or estrogen levels. Cases were significantly more likely to be bachelors or to work as butchers than were the controls. Other statistically significant risk factors identified were family history of breast cancer and therapeutic use of digitalis. Elevated risks, although not significant, were observed for individuals with a past history of tuberculosis, hyperthyroidism, liver cirrhosis or gallstone, who had been treated with isoniazid, or who had worked in high environmental temperatures. Further studies are needed to confirm our results particularly as regards hormonal imbalance and genetic factors. PMID- 2323843 TI - O-linked mucin-type glycoproteins in normal and malignant colon mucosa: lack of T antigen expression and accumulation of Tn and sialosyl-Tn antigens in carcinomas. AB - The expression of carbohydrate core-structures on O-linked glycoproteins was examined in fetal (n = 6), infantile (n = 2), normal adult (n = 15), and malignant (n = 22) colorectal tissue by means of monoclonal antibodies (MAbs) specific for Tn (GalNAc alpha 1-O-R), sialosyl-Tn (NeuAc alpha 2-6GalNAc alpha 1 O-R), and T (Gal beta 1-3GalNAc alpha 1-O-R) antigens. Immunolabelling of solubilized malignant tissue, separated by SDS-PAGE, showed expression of Tn and sialosyl-Tn antigens on 3 molecules of similar mw (230, 210, and 170 kDa), whereas no T antigens could be detected. Immunohistochemical techniques showed that fetal colon mucosa expressed Tn antigens but no sialosyl-Tn antigens. Infantile colon mucosa, however, expressed Tn as well as sialosyl-Tn antigens, and normal adult colon mucosa cells expressed no Tn antigens but sialosyl-Tn in 2 out of 6 biopsies from cecum, which indicates occurrence post partum of alpha-6 NeuAc-transferase. Endothelium in normal adult mucosa showed expression of both Tn and sialosyl-Tn antigens; 82% of carcinoma tissue sections expressed Tn antigens, and 73% expressed sialosyl-Tn antigens in mucin or cytoplasm, or on luminal cell membranes. T antigens could be detected neither in normal mucosa cells at any stage of development, nor in carcinomas. The possibility exists that this could be due to masking of T antigen. Mucin-type blood-group A antigens which contain an internal T-disaccharide were demonstrated in 4 out of 4 A1 tumors by means of MAb HH5. However, urea-containing SDS-PAGE analysis demonstrated an HH5 binding to molecules different from those binding anti-Tn. In remote morphologically normal and abnormal crypts in colons from carcinoma patients, both Tn and sialosyl-Tn antigens were expressed in secreted mucin in 40% of the cases. The data indicate an expression of O-linked Tn and sialosyl-Tn core structures in fetal and infantile colon and in colorectal carcinomas. PMID- 2323844 TI - DNA adducts in different tissues of smokers and non-smokers. AB - Purified DNA from human lung, liver, bladder, pancreas, breast and cervix has been analysed for DNA adducts using the nuclease P1 modification of the 32P post labelling technique. Tissues were obtained at autopsy from 13 men and 6 women. Relatives were asked to provide information on smoking history for deceased subjects. All tissues examined except the breast had detectable adducts. In lung, bladder and pancreatic tissue a characteristic pattern of adducts was seen which has previously been reported as typical of cigarette-smoke-induced damage. Smokers and former smokers tended to have higher adduct levels than non-smokers in the tissues examined but this was only significant for the lung. There appeared to be considerable variation in adduct levels among smokers which could not be accounted for by duration or daily consumption level. Certain smokers had high adduct levels in all tissues examined, whilst in others high levels were only seen in some tissues. All cervical samples examined had detectable adducts. These results confirm the finding that cigarette smoking is associated with DNA damage in the lung and suggest that similar damage may be related to tobacco induced neoplasms of other tissues. PMID- 2323845 TI - Cancer in Mali, 1987-1988. AB - Results from the population cancer registry in Bamako, Mali, for the years 1987 and 1988, are presented. The age-standardized incidence for all cancers is high compared with rates reported elsewhere in West Africa (119.6 per 10(5) in males and 88.3 per 10(5) in females), but the leading cancers in each sex are the same (liver cancer in males, cervix cancer in females). The incidence of stomach cancer is the highest recorded in Africa, while rates for lung cancer, although low, exceed those in earlier series from registries in the region. PMID- 2323846 TI - Alpha 1-antitrypsin and survival in pancreatic cancer. AB - The association between serum levels of alpha 1-antitrypsin (a1AT) at the time of diagnosis and survival was studied in a group of 44 patients with confirmed pancreas cancer. All 44 patients were followed until time of death, which occurred in all cases from pancreas cancer, with a median time of 3 months and a range of 0.5 to 16 months. Cox's proportional hazards model was utilized in the analysis controlling for sex, age and tobacco smoking. Males, older patients and smokers have higher fatality rates, but none of these relations was statistically significant. By contrast, there was a statistically highly significant association of increased levels of serum a1AT, at the time of diagnosis of the cancer of pancreas, with shorter survival; patients with serum a1AT higher by 100mg/100ml had a 57% higher fatality rate. These results indicate that serum a1AT represents a clinically interesting prognostic factor in pancreas cancer. PMID- 2323847 TI - Plantar melanoma: is the incidence of melanoma of the sole of the foot really higher in blacks than whites? AB - The overall incidence of malignant melanoma in black populations is considerably lower than that in whites. There have been repeated suggestions in the literature that black persons may have an increased incidence of melanoma of the sole, relative to whites, because among blacks with melanoma there is a high proportion with tumors of the sole of the foot. Whether this observed difference in site distribution represents a difference in incidence rates has never been demonstrated. Data on cancer incidence from 2 areas, western Washington State (1974-1983) and metropolitan Atlanta (1975-1984), were analyzed to examine this question. The annual area- and age-adjusted incidence of plantar melanoma was 1.7 per million per year for blacks and 2.0 per million per year for whites (relative risk for blacks as compared with whites = 0.88, 95% confidence interval = 0.36 2.11). These data argue that in North America there is little difference between blacks and whites in the incidence of plantar melanoma, and that the well known proportional difference appears to be due instead to the decreased incidence in blacks of melanoma on skin surfaces other than the soles of the feet. PMID- 2323849 TI - Differentiation-inducing and growth-inhibitory activities of erythroid differentiation factor (EDF/activin A) toward mouse erythroleukemic cells in vivo. AB - The in vivo differentiation-inducing activity of a purified human erythroid differentiation factor (EDF) toward mouse erythroleukemic cells (MEL cells) was examined. BDF1 mice with diffusion chambers implanted in the peritoneal cavity were treated with continuous i.p. administration of EDF. MEL cells within a diffusion chamber differentiated into hemoglobin-positive cells when treated with EDF, the percentage of the positive cells being 32.3 +/- 28.3 on day 5 as compared to 0.2 +/- 0.3 in the controls. The anti-tumor activity of EDF was also examined in a nude mouse MEL solid tumor model. Daily intra-tumor treatment with EDF for 10 days resulted in 73% suppression of tumor growth on day 25. A histological study revealed that EDF-treated solid tumor cells became hemoglobin positive, indicating the anti-tumor activity of EDF through induction of differentiation in vivo. EDF could induce in vitro the differentiation of human erythroleukemic cell lines K562 and HEL, as well as the murine cell line. These results indicate the possibility of differentiation therapy for erythroleukemia using EDF. PMID- 2323848 TI - Characterization of an embryonal rhabdomyosarcoma cell line showing amplification and over-expression of the N-myc oncogene. AB - A parent rhabdomyosarcoma cell line designated SCMC-RM2 was established from bone marrow tumor cells taken from an 11-year-old girl with an embryonal rhabdomyosarcoma. Subsequently a cloned SCMC-RM2-1 cell line was isolated from a parent line. These cell lines grew as adherent monolayers in liquid culture with a doubling time of 50 and 52 hr, respectively. In addition, colonies were established in soft agar, which grew in a dose-dependent fashion with a cloning efficiency of 0.7 and 0.8%, respectively. Chromosomal analysis showed these cell lines had neither double minutes nor homogeneously staining regions. Chromosome number ranged from 61 to 93, translocation; t(9;13)(p22;q14) was identified, and no alteration of chromosome 2 was observed. Surface membrane antigen profile of parent and cloned lines by using a panel of 24 monoclonal antibodies (MAbs) excluded the possibility of these being neuroblastoma cell lines. In addition, MAbs to the cytoplasmic protein desmin, myoglobin, muscle actin (alpha and gamma) and alpha-sarcomeric actin reacted with these cell lines, SCMC-RM2 and SCMC-RM2-1 being thus identified as rhabdomyosarcoma. Southern blot analyses revealed 8- and 7-fold amplification of the N-myc gene in SCMC-RM2 and SCMC-RM2-1 as compared with the promyelocytic cell line HL60. Over-expression of the N-myc mRNA was noted over control cell lines. PMID- 2323850 TI - In vitro and in vivo anti-tumor activity of L-glutamic acid gamma-monohydroxamate against L1210 leukemia and B16 melanoma. AB - A glutamine analogue, L-glutamic acid gamma-monohydroxamate (GAH) demonstrated complete cytotoxicity against L1210 cells in culture and marked anti-tumoral activity in vivo against L1210 leukemia and B16 melanoma. In vitro, GAH caused concentration-dependent inhibition of L1210 cell growth, with complete cell death being reached at 72 hr and at a 500 microM concentration. A minimal incubation time of 38 hr with 500 microM GAH was necessary to obtain complete cell death at 72 hr. During incubation, GAH is metabolized to hydroxylamine. Hydroxylamine acts as the active form of GAH, since the concentration-dependent inhibition of cell growth caused by hydroxylamine is the same as that observed with GAH. The cytotoxic effects of GAH and hydroxylamine on L1210 cells were not reversed or prevented by L-glutamine or L-glutamic acid and purine nucleosides but were prevented or reversed by pyruvate, 2-oxaloacetate and 2-oxoglutarate. In vivo, GAH considerably increased survival of mice bearing L1210 leukemia or a solid tumor, the B16 melanoma. Antitumor activity of GAH against L1210 leukemia and B16 melanoma was schedule-dependent. The administration of GAH 3 times daily was more effective than a twice daily treatment and the maximum ILS was observed using split-dose schedules on days 1 through 3 and 7 through 9 without noticeable toxicity. Under these conditions hydroxylamine is highly toxic, suggesting that in vivo GAH might act as an hydroxylamine releaser in the tumor cells and is not significantly metabolized in the body. PMID- 2323851 TI - Establishment and characterization of a continuous in vitro line from a rat choriocarcinoma. AB - A continuous in vitro cell line of rat choriocarcinoma has been established. It is composed of pure trophoblast cells which multiply and differentiate. The morphology of the cells is very similar to normal rat cytotrophoblasts and giant cells. The cultured cells contain cytokeratin, alkaline phosphatase and express the receptors for Bandeira simplificifolia Agglutinin-I (BSA-I). They are hormonally active as demonstrated by the presence of lactogen and progesterone in the supernatant of the culture. The injected cells develop into choriocarcinoma in syngeneic as well as allogeneic rats. The morphological, biological and immunohistochemical features of these tumors are identical to those described in the transplantable neoplasm from which the in vitro line was established. The presence of Y chromosome in cultured cells proves the paternal origin of the primary tumor developed from extra-embryonic membranes in fetectomized rat and makes this neoplasm similar to human post-gestation choriocarcinoma. PMID- 2323852 TI - Identification of T-cell antigens expressed by metastatic T-cell hybridomas and lymphomas. AB - Using the murine BW5147 tumor model system, we have identified 3 MAbs that discriminate between metastatic and non-metastatic BW5147-derived T-cell hybridomas and BW5147-unrelated T-lymphomas. The 3 rat MAbs appear to recognize an identical membrane-associated sialoglycoprotein with an approximate molecular weight of 95-100 kDa. We thus defined "metastatic T-cell hybridoma" antigens (MTH Ags) that are also expressed on normal T-lymphocytes. No correlation was found between the expression of the MTH Ags and in vitro invasive behavior of normal and malignant cells. Neither did we find any relationship between organ specificity of i.v. inoculated tumor cells and their MTH-Ags expression. It thus remains unclear whether our MTH-Ags are functionally involved in the metastatic process, or whether their expression is only incidentally related to the metastatic potential. PMID- 2323853 TI - Western blotting analysis for malignant lymphoma and stomach cancer antigens from carcinogen-transformed Bloom syndrome cells. AB - Membrane antigen (glyco-) proteins associated with malignant lymphoma (ML) and stomach (ST) cancer were collected from a carcinogen-transformed Bloom syndrome (BS) B-lymphoblastoid cell line by means of the panning protocol, in which antigen cell clones which specifically react with antibodies in ML and ST cancer sera were separated on polystyrene dishes coated with IgG. Gel electrophoresis and Western blotting (WB) analyses demonstrated that antigens which characterize ML and ST cancer gave a single band (ML, 97 kDa; ST, 118 kDa) and did not cross react with sera of other cancer patients or with normal sera. The present WB procedure may be useful for diagnostic purposes. The amino acid sequence of the ML antigen band (97 kDa) had 76.9% (in 13 sequences) homology to that of the variable region of the immunoglobulin (Ig) heavy chain (IgVH) at the N-terminal end, while the sequence of the ST (118 kDa) cancer antigen had little homology to IgVH. PMID- 2323854 TI - Low responsiveness of spleen cells from tumour-bearing mice to recombinant interleukin-1 and interleukin-2. Impaired expression of interleukin-2 receptors. PMID- 2323855 TI - A multidisciplinary approach to the study of the effects of altitude on muscle structure and function. AB - The aim of the papers included in the present series as well as the characteristics of the subjects participating in the study (16 mountaineers) are presented. The following studies deal with the effects of chronic hypoxia on muscle ultrastructure, enzymes, and energetics, as well as on oxygen transport and delivery during exercise. Most of the results appearing in the forthcoming papers were collected before and after two Himalaya expeditions (Lhotse Shar, 1981, and Everest, 1986) whose characteristics and duration are described. PMID- 2323856 TI - Muscular exercise at high altitude. PMID- 2323857 TI - Effect of chronic hypoxia on muscle enzyme activities. AB - Biopsies from the vastus lateralis muscle of seven participants in the Swiss expedition to Mt. Everest and Lhotse in 1986 were taken before departure to and after return from high altitude, and used for measurements of maximal activities of 12 reference enzymes of anaerobic and aerobic-oxidative metabolic pathways. The results indicated that strenuous exercise at high altitude induced increases in enzyme activities of glycolysis and decreases in enzyme activities of terminal substrate oxidation (the citric acid cycle, fatty acid oxidation, ketone body utilization, respiratory chain). The decreases in enzyme activities of aerobic oxidative metabolism were related to similar decrements in mitochondrial volume density, which suggests that the enzymic changes resulted from a loss of mitochondrial structure rather than from qualitative changes of the mitochondrial population. These changes indicated that strenuous exercise may intensify the stress of high-altitude exposure and, thus, induce an aerobic to anaerobic shift of muscle energy metabolism. PMID- 2323858 TI - Oxygen transport system before and after exposure to chronic hypoxia. AB - Maximal VO2 on the treadmill (VO2max) and on the bicycle ergometer (VO2peak), maximal cardiac output (Qmax), by a CO2 rebreathing method, maximal heart rate (HRmax), blood hemoglobin concentration (Hb), and hematocrit (Hct) were measured on six subjects before (B) and 3 weeks after (A) prolonged exposure to chronic hypoxia. It was observed that after high-altitude exposure VO2max, VO2peak, and Qmax were lower (P less than 005) than before [A: 4.13 +/- 0.67; 3.28 +/- 0.41 and 16.89 +/- 2.49 (l/min +/- SD); B: 4.39 +/- 0.39; 3.53 +/- 0.34 and 21.81 +/- 1.27, respectively], whereas Hb and Hct were larger (A: 162 +/- 8 g/l and 0.46 +/ 0.02; B: 142 +/- 7 and 0.41 +/- 0.02) and HRmax was unchanged (178 +/- 7 vs 175 +/- 9 bts/min). Thus, the calculated stroke volume of the heart and the Hb flow at VO2 peak were lower in A than in B (95 +/- 15 vs 124 +/- 7 ml and 2,723 +/- 307 vs 3,129 +/- 196 g/min) (P less than 0.05, respectively), whereas the arteriovenous O2 difference was greater in A than in B (195 +/- 16 vs 162 +/- 19 ml O2/l; P less than 0.05). At any given submaximal work load, VO2 and HR were the same in B and in A, whereas Q was lower in A by approximately 2-3 l/min. However, because of the increased Hb, leading to a higher arterial O2 content, at any work load the O2 flow remained unchanged. PMID- 2323859 TI - Aerobic performance at altitude: effects of acclimatization and hematocrit with reference to training. AB - The aim of the present investigation carried out on six members of the Swiss 1981 Mt. Lhotse Shar (8398 m) expedition was to assess the quantitative role of some of the determinants of VO2max at altitude. The loss of VO2max expected for the investigated altitude range was partially counterbalanced by the training undergone by the subjects during the approach to the base camp. delta VO2max was 18% instead of the expected 30%-35%. The VO2max value attained shortly after arrival at 5200 m was not significantly increased (38.4 +/- 4.4 SD vs 36.9 +/- 3.3 ml O2.kg-1.min-1) with a progressive rise of Hb from 16.4 +/- 0.8 to 18.2 +/- 1 g/100 ml of blood. Hemodilution, by oral administration of 2 liters of the isosmolar solution ISOSTAR, at 5200 m led to a 2.3% decrease of Hct and a 7.3% reduction of VO2max per kg of body weight. The product of heart rate times systolic arterial pressure ("double product") was somewhat (but not significantly) greater in hypoxia than in normoxia at all work loads. The maximum value for this product, however, was 10%-15% lower at 5200 than at 400 m. The increase of Hb from 15.1 +/- 0.7 to 17.1 +/- 1.6 g/100 ml of blood pre- to post expedition was not accompanied by a significant increase of VO2max determined at 400 m either absolute or per kg of body weight. PMID- 2323860 TI - The energetic significance of lactate accumulation in blood at altitude. AB - The O2 equivalent of lactic acid accumulation in blood was estimated from data on ten subjects acclimatized to altitudes up to 6500 m in the course of a Mt. Everest expedition. The calculated value of the O2 equivalent of La by standard least squares regression was 2.07 +/- 0.4 l O2 for a rise of blood lactic acid concentration [Lab] of 1 g per liter of blood (2.92 ml O2 per kg of body weight per 1 mM increase in blood lactate). This value, as well as the value obtained by the regression procedure suggested by Brace (2.84 +/- 0.5 l), was not significantly different from the previously reported value of 2.38 +/- 0.22 (14) for sea-level conditions. This finding indicated that, after La equilibrium is achieved, the redistribution of La among extra- and intracellular body compartments, as reflected by [Lab], appears not to be substantially affected by chronic hypoxia. The calculated maximum lactic O2 debt values at the Mt. Everest base camp (5350 m) were 1.26 and 1.42 liters for acclimatized Caucasians and for Sherpas, respectively. The amount of the measured maximum O2 debt at altitude was somewhat increased by pure O2 breathing (1.53 vs 1.26 l). PMID- 2323862 TI - Maximal muscular power before and after exposure to chronic hypoxia. AB - The maximal muscular power (both instantaneous, w, and average, w-.) and the cross-sectional area of the left thigh (CSA) were measured on six subjects before (B) and after (A) prolonged exposure to high altitude (above 5000 m asl). w and w were determined during a standing high jump off both feet on a force platform, and CSA by computed tomography. It was observed that: (1) in B, body weight (BW) = 74.1 +/- 5.8 kg, w = 3330 +/- 460 W (44.8 +/- 3.4 W.kg-1). w-. = 1795 +/- 395 W (24.6 +/- 4.3 W.kg-1), and CSA = 184.5 +/- 23.1 cm2; 2) in A, BW = 70.4 +/- 6.6 kg, w = 3005 +/- 472 W (42.5 +/- 3.6 W.kg-1), w = 1531 +/- 267 W (21.9 +/- 3.1 W.kg-1), and CSA = 163.5 +/- 23.1 cm2. Thus, w and w-. were decreased both in absolute terms (-9.8% and -14.7%, respectively) and per unit BW (-5.1% and 11.0%). However, because of the concomitant decrease in CSA, when expressed per unit cross-sectional area of the muscle, w (9.04 +/- 0.71 and 9.20 +/- 0.72 W +/- cm2) and w (4.87 +/- 0.81 and 4.70 +/- 0.67 W/cm2) were unchanged. The intrinsic capacity of the muscle to generate explosive power is therefore preserved in A. It is concluded that the decrease in w and w after high-altitude exposure depends only on a net loss of muscle mass. PMID- 2323861 TI - Morphological adaptations of human skeletal muscle to chronic hypoxia. AB - Muscle structural changes during typical mountaineering expeditions to the Himalayas were assessed by taking muscle biopsies from 14 mountaineers before and after their sojourn at high altitude (greater than 5000 m for over 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A significant reduction (-10%) of muscle cross-sectional area was found on CT scans of the thigh. Morphologically this loss in muscle mass appeared as a decrease in muscle fiber size mainly due to a loss of myofibrillar proteins. A loss of muscle oxidative capacity was also evident, as indicated by a decrease in the volume of muscle mitochondria (-25%). In contrast, the capillary network was mostly spared from catabolism. It is therefore concluded that oxygen availability to muscle mitochondria after prolonged high-altitude exposure in humans is improved due to an unchanged capillary network, supplying a reduced muscle oxidative capacity. PMID- 2323863 TI - Acral melanoma. A clinicopathologic study of 28 patients. AB - Clinical and histopathologic analyses of 28 cases of acral melanoma in the last 24 years were carried out in this study. Of our 81 patients with cutaneous malignant melanoma, 28 (35%) had acral melanoma. The mean patient age was 59 years old. The two most commonly involved sites were the soles and toes. The preferential sites for metastasis were the lymph nodes, followed by the lungs, bone, and liver in descending order. Histologically, all skin biopsy specimens showed biphasic growth patterns and consisted of either spindle cells or epithelioid cells or both. The treatment was in all cases mainly surgical and, in patients at advanced stage, chemotherapy was added. The mean survival time for the series was 34.03 months, while the 3-year survival rate was only 29%. PMID- 2323864 TI - Relationship between capillary and muscle damage in dermatomyositis. AB - To assess the pathogenetic importance of capillary damage and its relationship with degenerating muscle fibers in dermatomyositis (DM), an electron microscope study of eight muscle biopsy specimens (adult and juvenile forms) and seven muscle specimens from patients with other neuromuscular diseases was conducted. There was a 49% reduction of capillaries in the muscle specimens of DM patients. Capillary damage also was more frequent in the DM group than in control group (p less than 0.001). We found a striking relation between capillary and muscle damage in the DM group (p less than 0.002) but not in the control group. The diagnostic value of undulating tubules within endothelial cells is also discussed. PMID- 2323865 TI - Cronkhite-Canada syndrome. Light and electron microscopy of the cutaneous pigmentary abnormalities. AB - This article describes the light and electron microscopic studies from a macule and the surrounding lightly hyperpigmented skin of a patient with the Cronkhite Canada syndrome. Increased numbers of melanin granules in keratinocytes, increased numbers of melanosomes in melanocytes, and areas with increased numbers of melanocytes were found in the macular lesion. Skin from both the macule and surrounding area were also characterized by compact hyperkeratosis as well as perivascular inflammation and exocytosis not previously reported in these patients. PMID- 2323866 TI - Clinical and genetic study of xeroderma pigmentosum. AB - Seven patients with xeroderma pigmentosum are presented. Abnormal karyotyping, found in one case, could be associated with an increased risk of the development of neoplasia. PMID- 2323867 TI - Acrodermatitis enteropathica in Saudi Arabia. AB - Four patients with acrodermatitis enteropathica (AE) are presented from three Saudi families. The clinical picture in these patients is basically similar to that described elsewhere. These patients, however, showed different degrees of involvement of various body systems. In all cases, low serum zinc levels were documented, and they responded well to zinc supplementation. In the follow-up evaluation, angular cheilitis was observed as a feature that appears to herald the relapse of disease. Interestingly, when patients are treated, it was the last sign to disappear. Current information on zinc is summarized. PMID- 2323868 TI - Herpes gladiatorum in a male wrestler. PMID- 2323869 TI - Cutaneous bronchogenic cyst. PMID- 2323870 TI - Keratitis, ichthyosis, and deafness (KID) syndrome with adult onset of keratitis component. PMID- 2323871 TI - Progressive systemic sclerosis in a child. PMID- 2323872 TI - Cutaneous Mycobacterium malmoense infection in an immunocompromised patient. PMID- 2323873 TI - Toxic epidermal necrolysis associated with sulfonamides. PMID- 2323874 TI - Chloroquine and psoriasis. PMID- 2323875 TI - Acceleration of repigmentation in vitiligo by topical minoxidil in patients on photochemotherapy. PMID- 2323876 TI - Clinical trial of prostaglandin E2 on the oral lesions of pemphigus vulgaris. PMID- 2323877 TI - Dermatologic radiation therapy: Pyrex versus beryllium window units. PMID- 2323879 TI - Lichen planus: treatment of thirty cases with systemic and topical phenytoin. PMID- 2323878 TI - Trophic leprosy ulcers: treatment with topical and systemic phenytoin. PMID- 2323880 TI - Structural transition of bovine plasma albumin in the alkaline region--the N-B transition. AB - Bovine plasma albumin (BPA) has approximately one SH group (Cys-34) which catalyzes the intramolecular SH, S-S exchange reaction in the alkaline region at low ionic strength, resulting in the formation of the aged form. So, the N-B transition at ionic strength above 0.20 and below 0.10 was studied using BPA and iodoacetamide-blocked BPA (IA-BPA), respectively. (1) pH profiles of [theta]262 and [theta]268 of BPA in 0.20 M KCl showed the characteristic changes in the pH region 7.0-9.0, corresponding to the N-B transition. On going from pH 7.0 to 9.0 in 0.10 M KCl or NaCl, IA-BPA did not show significant changes in rotational relaxation times of tryptophyl fluorophors, CD-resolved secondary structures, spin-echo 1H-n.m.r. spectra and cross-relaxation times (TIS) between irradiated and observed protein protons, which might reflect the rigidity of the domains and/or subdomains. On the other hand, rotational relaxation times of 1-anilino-8 naphthalenesulfonate-IA-BPA complex (IA-BPA-ANS0.9, molar ratio of ANS to IA-BPA = 0.9/1) showed significant decreases from 131 to 114 ns on going from the N- to the B-forms in 0.10 M KCl. The above results and reported experimental evidence might indicate that on going from the N- to the B-forms in 0.10 M KCl or NaCl, the mutual movement of subdomains, connected with a flexible hinge region (Brown & Shockley (1982)) might increase without loss in the helicity and the rigidity of subdomains. (2) The N-B transition of IA-BPA in the absence of salt was quite different from those in 0.10 M KCl or NaCl. Decreases in the helicity and the intramolecular rigidity, as monitored by TIS-measurements, were observed on going from the N- to the B-forms. PMID- 2323881 TI - Conformational characteristics of legume 7S globulins as revealed by circular dichroic, derivative u.v. absorption and fluorescence techniques. AB - The 7S globulin storage proteins, phaseolin, vicilin, and beta-conglycinin of, respectively, dry bean, field pea, and soybean, are highly homologous, have similar predicted protein structures, and yet exhibit considerable differences in their susceptibility to various proteinases [Nielsen, S.S., Deshpande, S.S., Hermodson, M.A. & Scott, M.P. (1988) J. Agric. Food Chem. 36, 896-902]. These differences in their proteolytic behavior were studied in relation to their solution conformational states. The secondary structures of these three proteins determined by far u.v. circular dichroism were characterized by predominantly beta-sheet and beta-turn parameters. However, characterization of tertiary and quaternary structures using second derivative u.v. absorption spectroscopy, surface hydrophobicity using cis-parinaric acid as hydrophobic probe, and fluorescence quenching studies of intrinsic Trp fluorescence using an ionic (iodide) and a neutral (acrylamide) quencher indicated sharp differences in the conformation of these proteins. About 9.6 and 10.2 out of 13 and 15 tyrosyls/subunit of phaseolin and beta-conglycinin, respectively, were exposed to polar solvent, while the surface hydrophobicity varied beta-conglycinin greater than vicilin greater than phaseolin. The Trp residues in phaseolin were not accessible to iodide, while half those of vicilin and beta-conglycinin were quenched. The order of Trp accessibility to acrylamide was vicilin greater than beta-conglycinin greater than phaseolin. The relative compactness of these three proteins based on these studies was related to the observed differences in their susceptibility to various proteinases. PMID- 2323882 TI - Morphiceptin analogs containing 2-aminocyclopentane carboxylic acid as a peptidomimetic for proline. AB - As part of a program to study the structure-activity relationship of peptide opioids we report the synthesis, conformational characterization and biological activity of four analogs related to morphiceptin in which the proline at position two has been substituted with 2-aminocyclopentane carboxylic acid (beta Ae5c). The beta Ac5c residue is a beta amino acid with two chiral centers resulting in four possible configurations; two configurational cis (R,S and S,R) and two configurational trans (R,R and S,S) forms. Utilizing high resolution n.m.r. at 500 MHz and computer simulations with NOE restraints the chirality of the beta Ac5c residues are assigned. The analog containing the R,S-beta Ac5c is active at both the mu and delta-opioid receptors, with a slight preference for the mu receptor. The (S,R), (S,S), and (R,R) analogs show minimal activity at the mu receptor and are inactive at the delta-receptor. A comparison of the findings from the conformational analysis and biological assays lends insight into the structure-activity relationship of this important peptide opiate. PMID- 2323883 TI - Hormonotoxins. Effects of modifying the gonadotropin alpha-subunit on the generation of lutropin-toxin conjugates. AB - On the basis of the observation that in the hormonotoxin oLH-gelonin conjugation of the toxin occurs via the alpha-subunit of lutropin, an attempt was made to develop a general method for generation of similar hybrid proteins involving other glycoprotein hormones. In this approach sites suitable for conjugation would be first introduced into the alpha-subunit, hybridized with any native hormone specific beta-subunit of choice (LH-beta, FSH-beta, TSH-beta) following which the toxic component gelonin would be added on in the form of gelonin-S-S alpha---beta complex. Thus, thiolated lutropin alpha-subunit recombined well with free lutropin beta-subunit, yielding a hybrid which was active in terms of receptor binding, immunoreactivity, and steroidogenic properties. However, subsequent conjugation with thiolated gelonin, a ribosome inactivating protein, resulted in dissociation of beta-subunit from its non-covalent union with the thiolated alpha-subunit. It is concluded that the addition of positively charged gelonin at particular sites on the alpha-subunit led to the destabilization of the lutropin quaternary structure. PMID- 2323884 TI - Side reaction in peptide synthesis. Formation of oxazolidone derivatives. AB - 2-Oxazolidone derivatives formed through an intramolecular reaction in the process of alkaline treatment of urethane-type N-protected peptides of which the N-terminal residues were Ser or Thr having unprotected hydroxyl groups. In oder to avoid this side reaction, the esters of these peptides could be cleaved by enzymatic hydrolyses instead of saponification. PMID- 2323885 TI - Synthesis of cyclic peptide homologs of glutathione as potential antitumor agents. AB - Two cyclic tripeptide homologs, cyclo(Glu[Cys-beta-Ala-]-OH) 8a, and cyclo(Glu[Cys-Gaba-]-OH) 8b, were synthesized by the pentafluorophenyl ester method in solution. These cyclic peptides are cyclo homologs of glutathione and are designed as potential antitumor agents. The 1H- and 13C-n.m.r. spectral parameters of cyclo(Glu[Cys(Bzl)-beta-Ala-]-OH) 7a were measured in DMSO-d6 and a possible conformation has been proposed. The cyclic peptide 8a showed low cytotoxic activities against three human tumor cell lines: KB, HeLa, and Colo 205. PMID- 2323886 TI - Divalent metal ion mediated interaction of proteins with negatively charged membranes. A model study employing molecular mechanics. AB - Previous molecular mechanics calculations on the effect of Ca(II) and Mg(II) ions on the conformation of the 18-23 loop of bovine prothrombin [Maynard et al. 1988, Int. J. Peptide Protein Res. 31, 137-149] are extended to include the effect of a model phospholipid head group methyl[L-seryl] phosphate. Whereas the conformation of the Gla-21 Pro-22 amide bond remains decidedly trans in the absence of the model head group, in its presence, the cis Ca(II) ion induced (but not Mg(II] form is significantly lowered in relative energy. The low energy Ca(II) structures establish a coordination sphere with more ligands than do the low energy Mg(II) ion structures. PMID- 2323887 TI - Multiple peptide synthesis using a single support (MPS3). AB - An automated multiple peptide synthesis method to synthesize, cleave, and purify several peptides simultaneously in a single batch has been developed. The technique is based on the synthesis of multiple peptides on a single solid phase support and is easily adapted to manual or to automated methods. The approach relies on coupling of amino acid mixtures to the resin and it has been found that DCC/HOBt gives the best coupling performance. Fast Atom Bombardment Mass Spectrometry (FAB-MS) was used to rapidly and efficiently identify the peptides in each synthetic mixture which significantly assisted the purification process by HPLC. The method has been successfully applied to the synthesis of magainin 2 and angiotensinogen peptides. PMID- 2323888 TI - Peptide substrate specificity of the alpha-amidating enzyme isolated from rat medullary thyroid CA-77 cells. AB - The kinetic parameters were obtained for enzymatic alpha-amidation of peptides of the form N-dansyl-(Gly)4-X-Gly-OH, in which the amino acid at position X was substituted with each of the 20 natural amino acids. The enzyme used in these studies was a highly enriched preparation of alpha-amidating enzyme secreted by a clonal (CA-77) cell line which actively expresses mature alpha-amidated peptides. A 130-fold and 11-fold variation respectively in apparent Km and Vmax values was observed. The effect of the amino acid side chain at position X in stabilization of the enzyme-substrate complex decreased through the series X = planar aromatic or sulfur containing greater than neutral aliphatic greater than polar and basic greater than cyclic aliphatic or acidic. PMID- 2323889 TI - Synthesis, metabolic stability and chemotactic activity of peptide T and its analogues. AB - Acquired immunodeficiency syndrome (AIDS) is initiated by the attachment of the human immunodeficiency virus (HIV) to a surface glycoprotein CD4 present on T4 helper/inducer lymphocytes, monocytes/macrophages and other cells. A simple octapeptide (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH, peptide T) seems to inhibit HIV infectivity and to activate human monocyte chemotaxis. In order to study in vitro metabolic stability and structure-activity relationships, peptide T and a number of analogues were prepared and tested on human monocytes by chemotactic assay. Peptide T and the shorter fragments T(3-8)-OH and T(4-8)-OH displayed potent bioactivity (maximal chemotactic activity in the range 10(-11)-10(-10) M). The C-terminal heptapeptide showed a reduction of potency, while further truncations at N-terminus of T(4-8)-OH abolished the biological action. In the octapeptide series, whereas the alpha-amino butyric acid (Abu) substitution for Thr4 was well tolerated, the same "slight" structural change at Thr5 or Thr8 was very detrimental. Finally, [D-Asn6]T(1-8)-OH analogue has low chemotactic activity. All these results indicate that i) the C-terminal pentapeptide is the minimum sequence required for bioactivity, ii) residues 5 to 8 appear to play a crucial biological role, iii) peptide T chemotaxis is mediated, at least in part, through the polar properties of Thr side chains at the critical positions 5 and 8, while the Thr4 does not interfere with biological characteristics of peptides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2323890 TI - BOP reagent for the coupling of pGlu and Boc-His(Tos) in solid phase peptide synthesis. AB - The model peptide TRH was successfully synthesized using benzotriazol-1-yl-oxy tris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent). The coupling reactions were carried out in N,N-dimethylformamide or N-methylpyrrolidone. These solvents allowed the incorporation of the N-terminal pyroglutamic acid residue into the peptide chain, without using the derivative bearing the N benzyloxycarbonyl group, which acts as a solubility promoter. A comparative racemization study showed that Boc-His(Tos) can be coupled by means of BOP reagent with less racemization than with DCC when the amount of diisopropylethylamine (DIEA) is kept minimal (same ratio of equivalents as for Boc-His(Tos), i.e. 3 equiv.). However, with the use of a larger amount of DIEA in the coupling mixture (9 equiv.), approximately 3% of epimer was found in the crude product. Our study showed that even under low DIEA conditions, the rate of coupling of the residues with BOP remained comparable to that observed with DCC. PMID- 2323891 TI - A novel Fmoc-based anchorage for the synthesis of protected peptides on solid phase. AB - A novel bifunctional compound, 9-(hydroxymethyl)-2-fluoreneacetic acid, was synthesized, coupled to benzhydrylamine-resin, and evaluated for its application to the solid phase synthesis of protected peptide fragments. Anchor-bond cleavage was achieved with 15% piperidine/DMF. A protected heptapeptide, Boc-Val-Val Ser(Bzl)-His(Tos)-Phe-Asn-Lys-(Z)-OH, corresponding to the sequence (1-7) of rat transforming growth factor-alpha, was synthesized using this new support with an overall yield of 46%. PMID- 2323892 TI - Cotton-wool spots and AIDS related complex. AB - Twenty-nine patients with the AIDS Related Complex (ARC) were studied retrospectively. Cotton-wool spots (CWSs) were the main ophthalmological finding, present in 9 patients (31%) at this stage of the disease. The CWSs were asymptomatic and were therefore discovered during a routine examination. The proportion of patients with significant weight loss was greater among ARC patients with CWSs than among those with normal fundi. Leukocyte counts were found to be significantly lower (p = 0.03, odds ratio 10.0 [1.24 to 80.4]) among ARC patients with CWSs. Lymphocyte counts and the CD4/CD8 ratio were also found to be diminished in these patients. Among the nine patients with CWSs during ARC, seven developed major opportunistic infections or HIV (Human Immunodeficiency Virus) related neoplasias during the following months (3.8 +/- 3.5 months). These findings are consistent with a poorer prognosis for HIV infected patients who have CWSs. PMID- 2323893 TI - Experimental autoimmune uveoretinitis: idiotypic regulation and disease suppression. AB - Experimental autoimmune uveoretinitis (EAU), a mostly T-cell dependent disease, was induced in laboratory animals by a single immunization with retinal extract or purified S-antigen in complete Freund's adjuvant. It can be prevented or suppressed by injections of either the autoantigen or monoclonal antibodies against the autoantigen. The suppression of EAU by these antibodies was associated with an anti-idiotypic antibody response. The inhibition of the pathogenic immune response by the antigen or the antibodies could be explained, according to Jerne's hypothesis of immunoregulation, by a disturbance of the network of idiotype and anti-idiotype interactions. PMID- 2323895 TI - Abstracts presented at the first joint scientific meeting of the British and Italian Microcirculation Societies. Exeter, UK, 20-21 April 1989. PMID- 2323894 TI - Intravital observatories. Dream or necessity. AB - Among the major challenges confronting biomedical studies today two stands out above all others: 1. The need for a better interrelation of the remarkable findings of molecular and cell biology to living systems through careful intravital observation; and 2. The need for a more rapid and skillful application of the findings and methods of intravital observation to clinical applications. Major progress on either or both of these problems will require much greater emphasis on multidisciplinary studies of living animals involving a considerably wider variety of disciplines than has been brought to bear on them to date, plus the availability of the finest and most advanced technology. The cost in both money and manpower to achieve major breakthroughs is such that these goals can only be accomplished by having a few centers of excellence in which both a diversity of skills and of equipment can be made available to as wide a spectrum of the biomedical community as possible. It is the contention of this author that this can best be achieved by establishing a few methods-oriented centers of excellence for Intravital Observation which he has called Intravital Observatories. It is urged that the community of microcirculationists, which has long been a leader in a multidisciplinary approach to physiological studies and has made many of the outstanding advances in intravital microscopy, take the lead in making this major contribution to biomedicine. PMID- 2323896 TI - Blood flow determination by the laser speckle method. AB - Blood flow within the skin is measured by evaluating the dynamics of the laser speckle pattern. Laser light scattered from an object with a rough surface forms a granular structure--the speckles. When the object is moving, the speckle pattern becomes dependent on time. The measurements are performed at a distance of 6 cm which is adjusted by an auxiliary beam. The laser beam forms a spot on the skin with a diameter of approximately 1.5 mm and penetrates the skin. Part of the light is scattered back to the surface by the blood cells in the capillaries. The time dependent speckle intensity I(t) is determined by a photomultiplier. The comparison of spectra of I(t) obtained from measurements on the skin and on adhesive tape attached to the skin shows that there is a "tissue movement", the velocity of which has the same order of magnitude as the blood velocity in the capillaries. This has to be considered when measuring blood flow by the speckle method. Electronic signal processing reduces the influence from tissue movement and yields a value M being a relative measure of the blood flow. The time course of M during ischemia and reactive hyperaemia is compared with concurrent measurements of the skin temperature, the transcutaneous oxygen tension, and the laser Doppler signal. They exhibit similar tracings. Investigations in patients with leg ulcers show that measurements in open wounds can be performed. PMID- 2323897 TI - Wall structure of arteries and arterioles feeding the spinotrapezius muscle of normotensive and spontaneously hypertensive rats. AB - Vessel wall structure in feed arteries and their hierarchical ramifications were investigated in a rat skeletal muscle. Emphasis was placed on the transition of wall structure elements from the axillary and thoracodorsal arteries to the feeder arteries and the arcade and transverse arterioles forming the microcirculation of the spinotrapezius muscle. Semi-thin sections, prepared for light microscopy, and ultra-thin sections for electron microscopy were used to compare mature (15-20 week old) normotensive and hypertensive animals. The results demonstrate a gradual transition of the elastica intima and the smooth muscle from the central arteries towards the arterioles, accompanied by an attenuation of the adventitia. The elastica intima in 60-40 microns arcade arterioles is reduced from a continuous sheet in the central arteries to single fibers oriented parallel to the vessel axis. The multiple layers of smooth muscle cells at the level of the feeder arteries are reduced in the majority of arcade arterioles and in transverse arterioles to a single smooth muscle coat. Comparisons of the smooth muscle mass per unit length of vessel at selected sites of normotensive and spontaneously hypertensive rats show evidence for some degree of wall hypertrophy in the axillary artery, but no evidence for wall hypertrophy in arterioles of the microcirculation. There is no evidence of a pressure mediated structural medial wall hypertrophy along this peripheral vascular pathway. PMID- 2323898 TI - Temporal distributions of red cell supply rate to individual capillaries of resting skeletal muscle, in frog and rat. AB - Microvascular red cell (RBC) supply in resting skeletal muscle fluctuates with time and varies from capillary to capillary. Our aim was to quantitate this heterogeneity in two species (frog, rat) with very different oxygen requirements. Video recordings were made of RBC flow in capillaries associated with superficial fibers of frog sartorius and rat gracilis muscles, for periods of 2-10 min. RBC supply rate (cell/s) to individual capillaries was computed as the product of RBC 'content' (measured as lineal density, cells/mm, by a video-densitometric method) and RBC velocity (mm/s, measured by a spatial correlation technique). The videotapes were analyzed at rates of 6 to 15 samples per second. Regression analysis of the mean data showed little or no correlation between RBC content and RBC velocity (r2: frog 0.095, rat 0.002), both parameters contributing equally to variations in RBC supply rate. Temporal distributions of the three supply parameters demonstrate (1) the wide range of values present within each capillary, and (2) the symmetry of the distributions at high mean values versus a pronounced skewness as mean values approached zero. The wide range of mean values of each parameter, found in both species, suggests considerable 'spatial' heterogeneity of RBC supply among capillaries in resting muscle. Temporal heterogeneity of RBC supply rate to individual capillaries increased markedly as either velocity or content (or both) approached zero (overall mean coefficient of variation: frog, 62%; rat, 100%). Both species show remarkably similar rates of convective transport of RBCs per capillary in resting muscle (e.g. mean supply rates 3.2 and 6.2 RBCs/s in frog and rat, respectively). PMID- 2323899 TI - Microcirculation of the pancreas. A quantitative study of physiology and changes in pancreatitis. AB - A rabbit model was designed to study the microcirculation of the pancreas with special reference to changes occurring during acute pancreatitis. Intravital microscopy was used in conjunction with video techniques allowing for continuous observation and off-line evaluation of microvessel diameters and blood cell velocities. Based on the microvessel geometry a functional microvascular unit could be defined at the level of the pancreatic lobule consisting of intralobular arteries and veins and an arcade-like preferential pathway framing the capillary network. Experimental acute pancreatitis resulted in immediate leakage of the macromolecular plasma marker (FITC-Dextran 70) from the microvasculature suggesting increased permeability. In contrast to control conditions, pancreatic capillaries were excluded from the circulation during acute pancreatitis starting 30 min after induction with only single capillaries remaining perfused after 3 hours. At the same time, there was constant blood flow through the preferential pathways representing shunt perfusion. PMID- 2323900 TI - Nasopharyngeal pressure gradients during non-phonetic activities of the velopharyngeal valve. Part I. AB - The phonetic activity of the velopharyngeal valve has been the subject of electromyographic, radiological, ultrasonic, endoscopic, and of various acoustic and aeromechanical investigations. The subject of the present study was the non phonetic activities of the velopharyngeal valve. Ten patients were assessed by nasendoscopic examinations of the velopharyngeal valve. The pressure gradients in the nasopharynx during these activities were recorded. Typical individual nasopharyngeal pressure patterns were revealed inducing a development of a special technique and tests for a further study of the non-phonetic activities of the velopharyngeal valve in correlation with its abnormality and pathological speech activities. PMID- 2323901 TI - Nasopharyngeal pressure gradients during non-phonetic activities of the velopharyngeal valve. Part II. AB - The subject of our study is the non-phonetic activities of the velopharyngeal valve (VPV). The VPVs of 10 patients were assessed by nasendoscopic examinations. The nasopharyngeal pressure fluctuations were recorded by catheters placed into the nasopharynx. Simultaneous pressure created in the oral cavity was measured as well. In Part I we discussed the swallowing activities and here we describe sucking and blowing activities. The pressure wave tracings and measurements with the nasendoscopic examination provide us with new information which permits a further study of the non-phonetic activity of the VPV and a correlation with its abnormal speech activity. PMID- 2323902 TI - Occipito-mental side projection radiography in childhood maxillary sinusitis. AB - 152 sinuses of children with acute maxillary sinusitis were roentgenographically examined with both a standard occipito-mental (OM) and an occipito-mental side (OMS) projection. In the acute phase of the disease the OMS projection was superior in 13% of sinuses in demonstrating the presence of retained maxillary secretion. When the result of medical treatment was controlled after two weeks the superiority was seen only in 1% of sinuses due to the major difference between the subgroups' 'mucosal thickening'. The clinical importance of the OM finding 'mucosal thickening' seems to be different in the acute and in the follow up phase. From the clinical point of view single OM projection seems to be sufficient in most cases. However, the OMS projection seems to be a useful adjunct to or replacement of the standard OM radiogram in the acute phase of childhood maxillary sinusitis, if it is felt necessary to demonstrate the presence of retained secretion in spite of the increased radiation. When the result of treatment is evaluated, in unilateral cases OMS projection can replace OM projection. PMID- 2323903 TI - A staged laryngotracheal reconstruction using alloplast (Proplast) in the canine model. AB - Standard laryngotracheal reconstructive procedures are constrained by the availability of grafting materials and the ability to repair large defects. Reconstruction utilizing alloplasts may be ideal, but previous results have generally been poor. We present a two-stage procedure using Proplast to reconstruct large laryngotracheal defects in 6 dogs. A custom-made Proplast implant was inserted into a strap muscle pocket and buccal mucosa was placed in the adjacent peritracheal tissue. The muscle-Proplast composite graft was rotated to repair a large defect (3.25 cm by 2.25 cm). All 6 dogs survived. Endoscopic and histologic studies over 12 months showed continued stabilization and maturation of the implant. We feel that Proplast may be used as an alternative to autograft for reconstructing large laryngotracheal defects when the procedure is staged to allow maximal fibrous ingrowth and the implant is protected from infection. PMID- 2323904 TI - Fiberoptic laryngoscopy under general anesthesia in neonates. AB - In the Sophia Children's Hospital we perform fiberoptic laryngoscopy in neonates under general anesthesia without the use of muscle relaxants in the diagnostics of functional laryngeal disorders. The necessary diagnostic and anesthetic equipment is described. Special attention is paid to the way in which the fiberscope is introduced into the breathing circuit and into the child's airway. Several advantages over other methods are discussed. The procedure has proved to be easy, safe and informative. PMID- 2323905 TI - Childhood deafness in Portugal--aetiological factors and diagnosis of hearing loss. AB - The most common identified causes of hearing impairment in children are described based on the analysis of 1024 cases observed for a period of 4.5 years (1985 1989) at the ENT Department of the University of Lisbon. The values of mean ages of suspicion and diagnosis are indirectly used to assess the performance of the health care system concerning diagnosis of childhood deafness. Improvement of diagnostic age has been very important over the last years, due in part to an enormous increase in information and motivation of general practitioners and pediatricians which has been organized by the ENT Department of the University of Lisbon. Finally, the authors highlight the otorhinolaryngologist's important role in promoting the involvement of the different specialties for early diagnosis, correct management and prevention of childhood deafness. PMID- 2323906 TI - A case of facial diplegia associated with acute bilateral otitis media. AB - A 32-month-old toddler developed facial diplegia in association with a bout of acute bilateral otitis media. After 28 days of antibiotic therapy and placement of tympanostomy tubes, the patient demonstrated 100% symmetrical recovery. A brief discussion of the pathophysiology is included. PMID- 2323907 TI - Preventing postoperative complications in the adult cystic fibrosis patient. AB - Herein we report on a 27-year-old cystic fibrosis (CF) patient who developed bronchospasm, secretory plugging of the trachea, and pneumothorax following general endotracheal anesthesia for intranasal polypectomy and bilateral Caldwell Luc procedures at an adult facility. Intranasal polypectomy and paranasal sinus procedures are the most common surgical procedures performed on cystic fibrosis patients, making the otolaryngologist a frequent member of the cystic fibrosis team [8]. As survival improves, the pediatric otolaryngologist will find himself following CF patients into their 20's and 30's. Adult care facilities may not be as familiar with these patients as the surgeon would like. The otolaryngologist's familiarity with the unique perioperative requirements of the CF patient can prove invaluable in such a setting. Preoperative assessment should identify any acute pulmonary changes, assess nutritional status, assure good control of blood glucose levels, and rule out clotting abnormalities. Good perioperative hydration and meticulous attention to pulmonary toilet are of foremost importance in the surgical care of the cystic fibrosis patient. Chest physiotherapy and suctioning of the tracheobronchial tree should precede arousal from anesthesia and extubation. By insisting on appropriate anesthetic and perioperative care, the knowledgeable otolaryngologist may circumvent potential postoperative complications in the cystic fibrosis patient. PMID- 2323908 TI - Infantile hemangiopericytoma of nasal cavity. AB - Hemangiopericytoma is an uncommon vascular tumour. Of the 26 intranasal hemangiopericytomas reported in the English literature only two paediatric cases have been noted. A benign course is more common in the nose and paranasal sinuses. A pre-operative diagnosis being not possible, definitive treatment cannot be preplanned. Wide surgical excision by a lateral rhinotomy approach is still the treatment of choice. The appropriate investigations and treatment line followed are described. A lifelong followup is mandatory. PMID- 2323909 TI - Maxillary myxoma in children. AB - Myxoma of the maxilla is a rare, slowly growing, benign mesenchymal tumor. Pathologically, it may be difficult to differentiate from other tumors with myxoid stroma and is occasionally misinterpreted as malignant. This tumor is particularly uncommon in children; in a search of the literature, we were able to document only 17 cases of myxomas in the maxilla in patients aged 14 years or less. This report on two children with myxoma of the maxilla emphasizes the importance of including myxoma in the differential diagnosis of children with maxillofacial tumors, and underlines the difficulties in making a correct diagnosis. PMID- 2323910 TI - Peroxidase from Astragalus maritimus: purification and properties. AB - A peroxidase has been purified to homogeneity from Astragalus maritimus seeds using ammonium sulfate precipitation and chromatography on DEAE-cellulose and hydroxylapatite. The purification obtained was 255 fold. The enzyme preparations were homogenous by the criteria of SDS-PAGE and analytical gel electrofocusing. The protein contained 0.11% of iron that corresponds to a minimum molecular size of 50,700. Determinations of molecular size by SDS-PAGE gave values of 48,000 +/- 1,000 while the one obtained by Sephadex gel filtration was 49,000. The pH optimum of the enzyme was 6.0. The activation energy was estimated to be 6 Kcal/mol. The prosthetic group was shown to be ferriprotoporphyrin IX. The presence of 13% neutral sugars was found. The spectrophotometric analysis showed the presence, in the visible region, of absorption maxima at 403, 490 and 633 nm. The Rz value (A403/A275) was 2.7. PMID- 2323911 TI - Kinetic behaviour of soluble and mitochondrial bound lactate dehydrogenase. AB - Rabbit liver mitochondrial fraction shows lactate dehydrogenase activity. The kinetic behaviour of mitochondrial bound enzyme fits a bibi sequential type mechanism as well as the cytosolic rabbit liver lactate dehydrogenase. The bound enzyme has greater values of Km(NADH) and Km(pyruvate) than the soluble one, suggesting that binding induces a decrease in the affinity of both substrates. The behaviour of the free and the mitochondrial-bound enzyme is of the Michaelis Menten type, but the kinetics of a mixture of rabbit liver cytosolic and mitochondrial-bound lactate dehydrogenase is sigmoidal, suggesting that a cooperative phenomenon takes place. PMID- 2323912 TI - Advances in the pharmacology of headache. A symposium of the AASH at its 31st annual meeting. Boston, June 16, 1989. Proceedings. PMID- 2323913 TI - Brainstem auditory evoked potentials in migraine--evidence of increased side differences during the pain-free interval. AB - Brainstem auditory evoked potentials (BAEPs) were recorded in 38 unselected patients (6 m./32 f.; age 18-54 yrs.) with various forms of migraine, during the pain-free interval. The values were compared to those of 50 control persons (18 m./32 f.; age 17-75 yrs.). Peak latencies (PL I-VI), interpeak latencies (IPL I III, III-V, I-V) and side differences of all peaks (delta I-VI) were calculated. In contrast to PL's of migraine patients, all PL's of control persons were normally distributed. In 6 migraine patients (2 with basilar migraine) PL's were pathologically delayed. Statistical analysis did not show any significant difference in regard to PL's and IPL's between migraine patients and controls. However, side differences of all peaks (except peak IV,VI) were significantly increased in migraine patients as compared to controls. Our results indicate a slight but permanent impairment of brainstem function in migraine. PMID- 2323914 TI - Transient asymmetries of steady-state visual evoked potentials in classic migraine. AB - Unilateral abnormalities in the regional cerebral blood flow (rCBF) and visual evoked potentials (VEPs) during the visual aura of classic migraine have been reported. On the other hand, there are only few observations suggesting unilateral abnormality of neural function during the headache-free period. An experiment is described in which the symmetries of steady state VEPs (SVEPs) are compared in healthy subjects and classic migraineurs in the headache-free interval. In the patients an increased number of strong short-lasting interhemispheric asymmetries was found. In the serial recordings performed, pathologic recordings were obtained intermittently, usually with complete normalisation in the following session. The incidence of abnormalities was relatively independent of the interval between the recording and attack, except for the next few hours. The findings may be related to instability of occipital cortical function in classic migraine. PMID- 2323915 TI - Basilar artery migraine stroke. AB - A 25-year-old woman with a history of basilar migraine attacks ultimately resulting in a basilar artery migraine stroke is described. Brain computed tomography showed bilateral hypodense lesions in the cerebellar hemispheres. A survey of literature on basilar artery migraine is presented and the relation between stroke and migraine is discussed. PMID- 2323916 TI - Cluster headache: the relation to arousal, relaxation, and autonomic tone. PMID- 2323917 TI - Specific headache phenomena: their frequency and coincidence. AB - The correlation of specific headache attack characteristics derived from a standardized questionnaire was studied in a consecutive series of 392 patients attending a headache clinic. In patients reporting headache with aura such attacks tended to be infrequent, and the percentage of their headache attacks that were preceded by aura varied widely, many cases having very low percentages. Paresthesias as auras were uncommon and rarely occurred without visual aura. Unilateral headaches were associated with nausea to widely varying degrees. Most patients reported both unilateral headache and headache with tension characteristics. Definite history of hypertension was significantly correlated specifically with migraine with aura (classic migraine). PMID- 2323918 TI - Methionine-enkephalin in migraine and tension headache. Differences between classic migraine, common migraine and tension headache, and changes during attacks. AB - We measured methionine-enkephalin (MET) in platelets and platelet-poor-plasma of drug-free patients with classic migraine, common migraine or tension headache (TH). Migraineurs were studied both between and during attacks. TH patients were characterized by low platelet-MET and high plasma-MET levels, whereas migraine patients showed high platelet-MET and reduced plasma-MET levels. During migraine attacks both platelet and plasma-MET concentrations increased considerably. We suggest that determination of MET levels in platelets and plasma may be a useful marker to discriminate between TH and common migraine. The rise in MET during attacks may be directed against the ictal increase of serotonin. PMID- 2323919 TI - Influence of quality of life and stress coping behaviour on headaches in adolescent male students: an explorative study. AB - Quality of life (QL) and stress coping behaviour were evaluated in 194 adolescent male students, and related to their headache complaints. Negative correlations were found between headache duration and intensity versus satisfaction with autonomy, and between headache intensity versus satisfaction with the home situation. Both headache duration and intensity were found to correlate positively with depressive stress coping behaviour. Further, positive correlations were found between palliative and avoidant stress coping strategies versus headache intensity. Our findings suggest that active rather than passive stress coping strategies are effective in reducing headache intensity. In addition, this study indicates the relevance of focussing future research into headaches in adolescents on the home situation. PMID- 2323920 TI - Magnesium and migraine. PMID- 2323921 TI - Beta and electron dose calculations to skin due to contamination by common nuclear medicine radionuclides. AB - We present dose calculations to the basal cell layer of the epidermis resulting from skin contamination by radionuclides used in nuclear medicine. Dose calculations were made using the computer code VARSKIN, as modified by us to include these radionuclides and to account for their monoenergetic electron emissions. Results indicate that basal skin doses (taken to be at a depth of 0.007 cm) are approximately 1 cGy h-1 per 3.7 X 10(-4) Bq cm-2 (1 rad h-1 per muCi cm-2) from 99mTc, 111In and 201Tl, implying that established limits may be approached under certain circumstances. The implication of these results for small areas of contamination is also discussed. PMID- 2323922 TI - Effect of bedside shielding on air-kerma rates around gynecologic intracavitary brachytherapy patients containing 226Ra or 137Cs. AB - An anthropomorphic phantom was implanted with 226Ra or 137Cs gynecologic intracavitary brachytherapy sources. Air-kerma rate measurements were taken at 10 cm increments along a horizontal plane from the side of the bed at 50 cm, 87 cm, and 136 cm heights above the floor. Five portable lead shields were placed at the head, at the foot and along one side of the bed and readings were taken again at the corresponding heights above, below and behind the shields. The readings were normalized to 100-mg Ra equivalence, and air-kerma rate curves were drawn allowing for the comparison of 226Ra and 137Cs with and without lead shields. The data demonstrated that the air-kerma rates for 137Cs were reduced more than those for 226Ra with the use of the portable lead shields. There was four times the transmission with 226Ra than with 137Cs. The optimal placement was with the lateral bedside shields proximal to the head and foot closest to the bed, with the middle shield overlapping in back. The shields at the head and foot should extend out and overlap the bedside shields. The level of the sources should be positioned near the bottom of the shields. This information will provide the medical health physicist with an estimate of air-kerma rates for both 226Ra and 137Cs with and without shielding for evaluating personnel exposures as well as the effectiveness of current shielding in relation to radiation protection requirements in adjacent rooms or hallways. PMID- 2323923 TI - The COMPLY computer program for demonstrating compliance with national radionuclide air emission standards. AB - The Environmental Protection Agency (EPA) has proposed national radionuclide air emission standards for a number of source categories. One of these standards applies to Nuclear Regulatory Commission Licensees and non-Department of Energy facilities having the potential to release radionuclides to the atmosphere. Approximately 6000 facilities are subject to the standard, which limits the effective whole-body dose commitment to the maximally exposed individual from radionuclide releases to the atmosphere. A computer program to assist the regulated community in determining compliance has been developed by the EPA's Office of Radiation Programs. The computer program COMPLY calculates the dose to an individual residing outside the facility. The program considers dose from inhalation, ingestion of contaminated food, air immersion, and ground deposition. It is based on models developed by the National Council on Radiation Protection and Measurements (NCRP). Compliance procedures provided in COMPLY are designed to reduce the burden on the regulated community. The approach begins with simple-to use methods that are very conservative in determining compliance. The methods become progressively less conservative but more complicated at succeeding levels. Each higher level requires the input of site-specific information, but allows a more realistic estimate of dose. This paper describes the COMPLY program, and provides estimates of the work required and the degree of conservatism in the dose computed at each level. PMID- 2323924 TI - Statistical analysis of gamma-emitting radionuclide concentrations for three fields in southern Saskatchewan, Canada. AB - During 1988, the spatial variability of the natural gamma-emitting radionuclides (238U, 232Th, and 40K) and the artificial radionuclide 137Cs were studied in three near-level unfertilized fields in Saskatchewan, Canada. One field was used as a native (uneroded) control site; the other two sites have been cultivated, one since 1979 and the other since at least the 1940s. The two cultivated sites have been eroded by aeolian processes and tillage practices. Autocorrelation analysis indicated that most of the radionuclides were not serially correlated for the two depth increments sampled (0-15 cm and 15-30 cm). Autocorrelation is a necessary procedure when equally spaced transect sampling is employed, since sample independence cannot be assumed. Robust and nonrobust statistical summaries are presented for the selected gamma-emitting radionuclide concentrations. Robust statistical estimates of location and dispersion are favored when distributions are not normal or when the distribution is skewed. Median concentrations for the three fields indicated that 238U, 232Th, 40K, and 137Cs were similar to areas in the U.S. and to other areas in southern Saskatchewan. Median 238U activity concentrations were between 31.4 and 34.1 Bq kg-1; 232Th concentrations were between 29.6 and 31.2 Bq kg-1; 40K concentrations were between 471 and 502 Bq kg 1; and 137Cs concentrations were between 10.0 and 12.6 Bq kg-1. The variability of natural radionuclides in a given field for a specific depth increment was generally low, with coefficients of variation less than or equal to 10%. The variability of 137Cs concentrations was greater, ranging from 18% to 23%. Nonparametric tests indicated a significant decrease in 214Bi concentration (238U indicator corrected for 222Rn) with depth of the 1979 field, and an increase in 228 Ac (232Th) with depth in the 1940s field. Significant differences in concentration between fields were indicated for all radionuclides except for 228 Ac. The possible reasons for differences in depth and between fields are briefly discussed. PMID- 2323925 TI - Radionuclide uptake and growth of barn swallows nesting by radioactive leaching ponds. AB - Populations of barn swallows (Hirundo rustica) nested seasonally near the Test Reactor Area (TRA) radioactive leaching ponds on the Idaho National Engineering Laboratory (INEL). These birds utilized leaching pond arthropods as a food source and contaminated mud for nest construction and thus accumulated radioactive materials. Over 20 fission and activation products were detected in immature and adult TRA birds. The radionuclide exhibiting the highest mean concentration in adult birds was 51Cr, with 16.1 Bq g-1 (435 pCi g-1). Mean concentrations of detectable radionuclides were used to calculate internal dose rates. Approximately 72% of the total dose rate of 219 microGy d-1 (22 mrad d-1) for adult birds was due to 24Na. Swallow thyroids contained a mean 131I concentration of 3330 Bq g-1. An average dose rate to the thyroid was calculated to be 4300 microGy d-1 or 450 mGy (45 rad) for the entire breeding season. Data from LiF-700 thermoluminescent dosimeters in swallow nests indicated that average dose rates were 840 microGy d-1 for eggs and 2200 Gy d-1 for nestlings, for a total of 54 mGy (5.4 rad) during the nesting period. The breeding biology and growth rate were investigated for TRA swallows and comparison group located 15 km and 100 km away. Total mortality rates for the comparison group vs. 1976 and 1977 TRA populations were not found to be significantly (p greater than 0.9) different. Nonlinear regression was used to fit individual growth curves and estimate parameters using a logistic model. First clutch TRA swallows were found to have a significantly (p less than 0.05) lower mean growth rate compared to either the first clutch comparison group or the second clutch of TRA birds. Mean asymptotic weights achieved by immature TRA birds were also found to be significantly (p less than 0.05) lower than those achieved by comparison group birds. Both growth rate and asymptotic weights for TRA birds were within the normal range reported in the literature. The cause for the statistical difference in growth rate between the comparison group and TRA first clutch populations could not be determined. PMID- 2323926 TI - Radionuclide concentrations in the northern part of The Netherlands after the Chernobyl reactor accident. AB - Concentrations of radionuclides originating from the Chernobyl reactor accident were measured as a function of time in air, rainwater, grass, cow's milk, vegetables and dust by means of high-resolution gamma-ray spectroscopy. Special attention was paid to grass and milk originating from the same meadows. Also, milk of cows temporarily kept inside after the accident was monitored until a few days after their release from the stables. Activity ratios in various types of samples and the implication of the sheltering measures for cows are discussed. PMID- 2323927 TI - A practical E-PERM (electret passive environmental radon monitor) system for indoor 222Rn measurement. AB - The technical and scientific basis for the measurement of indoor 222Rn concentration using an E-PERM (Electret passive environmental radon monitor) has been described in our earlier work. The purpose of this paper is to describe further development of a practical and convenient system that can be used routinely for indoor 222Rn measurement. The ion chamber is now made of electrically conducting plastic to minimize the response from natural gamma radiation. A spring-loaded shutter method is used to cover and uncover the electret from outside the chamber. The electret voltage reader has been modified to improve the accuracy and the ease in operation. The calibration, performance, error analysis, and lower limits of detection for these standardized versions of E-PERMs are also described. PMID- 2323928 TI - Contamination of a soft-drink manufacturing plant by 210Po. AB - An investigation was undertaken of the contamination of equipment and flooring by 210Po, released from a static eliminator source, at a soft-drink manufacturing plant. The detection and establishment of extent of contamination, development of decontamination and control procedures and difficulties in implementing those procedures are discussed. Additionally, the likely health effects to workers are assessed. The removal and disposal of contaminated equipment, the use of epoxy compound on the floor to seal fixed contamination and the implementation of a 5-y monitoring program are detailed. The estimated cost of decontamination is provided. PMID- 2323929 TI - Long-term clearance of inhaled UO2 particles from the pulmonary region of the rat. AB - This paper reports on an enriched uranium dioxide (UO2) mass clearance study undertaken with Fischer-344 rats. The UO2 had a uranium (U) isotopic composition of 0.79% 234U, 92.8% 235U, 0.34% 236U and 6.06% 238U, by mass, with an alpha particle activity of 1.91 Bq micrograms-1. Forty-six rats were exposed to an enriched UO2 aerosol that had an activity median particle aerodynamic diameter ranging from 2.7 to 3.2 microns. The rats were killed from 1 to 720 d post inhalation (PI). The mass of enriched UO2 present in the trachea, lung lobes, thoracic lymph nodes, kidneys, liver, spleen, gut, and the remainder of the carcass was assessed at death. At 720 d after exposure, 82% of the total body burden of enriched UO2 was in the lung, with a further 10% in the thoracic lymph nodes. This represented 17% and 2% of the original (5 d PI) lung burden. The mass clearance of enriched UO2 from the lung was fitted to a single exponential function, normalized to 100% at 5 d PI. The rate constant (k) was 2.8 X 10(-3) d 1, giving a clearance half-time of 247 d. Although statistical comparisons with the majority of published data were not possible, it appeared that both enriched UO2 and natural UO2 particles cleared at rates that were broadly similar, with a t1/2 in the rat lung of 150 to 300 d over the 5- to 720-d PI period. As a consequence of the 234U component in the inhaled UO2 particles, the rats killed at 720 d PI received a total mean accumulated alpha-particle dose averaged over the whole lung of 5.7 Gy. Histologic investigations of the rat lungs found that widespread lung disease was only observed in animals killed at 720 d PI. PMID- 2323930 TI - Power-frequency magnetic fields from electric blankets. AB - Power-frequency (50/60 Hz) magnetic fields produced by electric blankets are estimated from data on blanket design using a three-dimensional computer model. Maximum, minimum, and volume-average fields within human forms are presented as a function of blanket type and a number of geometric factors including body size, body-blanket separation, and lateral body position. When blankets are heating, typical flux densities range from a few tenths of microtesla (microT) on the side of the body farthest from the blanket up to a few tens of microtesla on the side closest to the blanket. Superposition results in local minima within the body that approach zero field intensity. Across the blanket-using population, flux densities averaged over the whole body range from 1.5-3.3 microT with typical values of 2.2 microT. PMID- 2323931 TI - Guidelines for an effective radiation safety program in a human immunodeficiency virus (HIV) laboratory. PMID- 2323932 TI - Polonium-210 measurements in human semen. PMID- 2323933 TI - Distribution and alpha radiation dose from naturally occurring U, Th, and Ra in the human skeleton. PMID- 2323934 TI - Refinery kerosene contaminated by 210Po from a U mill processing facility. PMID- 2323935 TI - A comparison of EPA screening measurements and annual 222Rn concentrations in statewide surveys. PMID- 2323936 TI - Bremsstrahlung spectra from 32P electrons incident on Pb and Lucite. PMID- 2323937 TI - Chernobyl fallout radionuclides in Utah residents. PMID- 2323938 TI - On limitations of applicability of the one-group theory. PMID- 2323939 TI - Cylinders with unmixed helium/oxygen. PMID- 2323940 TI - Bead leaks in air-fluidized beds. PMID- 2323941 TI - [Covering physician system in the regional hospital]. AB - 1. At first the socio-political context is shown. Equality and inflation of demands have their price in the modern society of prosperity. Health, however, has become number one in our demands. 2. Nearly half of all the 700 surgeons of Switzerland are working in public hospitals. A few more than the other half are in private practice. Stationary surgery is done either in a public hospital or in a private clinic, the last one being either subsidized or not. 3. All the hospitals for surgical formation and the places with private hospitals are mentioned. 4. "Belegarzte" treat their patients in their private practice and operate on them, when they become stationary, in all the three types of hospitals cited above. 5. An analysis of the status quo is thought to prepare the questions for the following round table discussion, which might show us new ways in between tradition on one hand and alteration and futurism on the other hand. PMID- 2323942 TI - [Health politics considerations of the covering physician system]. PMID- 2323943 TI - [The private clinic and the covering physician]. AB - The "AMI-Klinik Im Park" opened in November 1986 as the fourth private hospital owned by American Medical International Inc. in Switzerland. The hospital is working with free practising doctors exclusively. There are rooms for private and semi-private patients. Well trained personnel, the latest medical equipment, medical supervision around the clock and the ICU make diagnosis and treatment of most illnesses possible. The medical specialties represented in the hospital, the ability to admit emergencies and the quality control of all services changed the traditional image of a private clinic to a hospital for general acute care with "University level". PMID- 2323944 TI - [Hospitals with the covering physician system in agglomeration]. AB - In Switzerland there are more than 700 practising surgeons. About 50% work at private hospitals as independent doctors and have special arrangements with the clinics. Independent surgeons and private hospitals represent a mutually dependent unity, which has stood the test for over 100 years. In Zurich, there are 120 private doctors practising as general surgeons or as specialists. Independent surgeons have about 600 beds available at clinics throughout Zurich. The increasing demand for additional insurances indicates that there is a trend among patients to get private treatment. To meet this growing demand, existing hospitals must expand and new clinics have to be built. Unfortunately, independently practising doctors can only treat a limited number of hospitalized general patients. There is a balance between doctors at public hospitals and independent surgeons. In order to conserve a free, independent medical profession, this balance has to be fostered in a mutually understanding way. PMID- 2323945 TI - [Traumatology in private practice]. PMID- 2323946 TI - [Heart center surgery in the private hospital: heart surgery in the hospital with covering physicians]. AB - Based upon the experiences at the "Herzzentrum Hirslanden" Zurich it is demonstrated that heart surgery and invasive cardiology, including cardiac catheterization and PTCA, can readily be performed by surgeons and cardiologists in private practice at a private hospital not receiving any government funds. The needs for additional heart surgical beds in the greater area of Zurich is confirmed. Manpower needed and necessary apparative infrastructure are discussed and present activities at the "Herzzentrum Hirslanden" illustrated. Finally problems with medical insurance companies covering the cost are dealt with. PMID- 2323947 TI - [Surgery of primary bronchial cancer. Different types of excisions: technical problems, follow-up results--status of pneumonectomies extended to the carina and bronchial resection-anastomoses]. AB - Surgery is the best solution for primary lung cancer. Surgery must be very large when necessary and must be as limited as possible when pulmonary function is poor. Surgery obtains the best results in primary lung cancer but must be associated with adjuvant therapy when necessary and specially in N2 tumors. In our experience in Marie Lannelongue Center we operated 5890 primary lung cancers between 1966 and 1987 (2255 lobectomies and 2240 pneumonectomies). Our long-term results are 38% at three years and 31% at five years. Extended surgery has been done in many patients. Chest wall resection is used when necessary associated to the lung resection. Carina resection must be used also if necessary. In our experience of 46 pneumonectomies with carina resection the five-year survival is 20% and 41% only for the N1 tumors. When there is involvement of the mediastinal ipsilateral nodes we try to do surgery as often as possible (mediastinoscopy is used very routinely now). On 284 N2 primary lung tumors operated between 1982 and 1988 the five-year actuarial survival is 18%. When the pulmonary function is poor we perform lung lobectomies with sleeve resection (114 sleeve resections on the 2255 lobectomies). The postoperative morbidity and mortality is very low in our experience, and the five-year survival is very good (about 40%). PMID- 2323948 TI - [Torsion of a corner of the omentum as a cause of acute abdomen]. AB - A torsion of the omentum with consecutive necrosis as a cause of acute abdominal pain or as a differential diagnosis of acute appendicitis is a rare finding. An overlook over the literature shows that since the first description of segmental necrosis of the omentum by Eitel et al. in 1899 only 300 cases were published. We report over another case, describe the clinical findings and the clinical symptomatology. PMID- 2323949 TI - [Injuries of the small and large intestine following blunt abdominal trauma]. AB - From 1979 to 1987 1428 patients with blunt abdominal trauma were treated in the Department of Surgery of the University of Freiburg; 119 patients had intestinal injuries. They were mainly young adults who had sustained a car accident. 71.3% of the small bowel injuries were overseen, 14.2% needed resection, and in 14.5% an operative procedure was not necessary. The surgical procedure for colonic injuries has to be chosen with regard to the age and general condition of the patient, to the severity of the trauma, to associated injuries and to the stage of peritonitis. Accordingly, 18% of the patients were treated with and 58% without a protective colostomy, 24% could be treated conservatively. Mortality and morbidity correlated with the severity of associated injuries. Morbidity was also dependent on the time interval between accident and operative therapy. PMID- 2323950 TI - Distribution of microtubules and microfilaments in thyroid follicular epithelial cells of normal, TSH-treated, aged, and hypophysectomized rats. AB - We investigated the distribution of microtubules and microfilaments in rat thyroid follicular epithelial cells by applying an immunofluorescence technique with monoclonal antibodies against tubulin and by staining sections with rhodamine-phalloidin. In normal thyroid cells, microtubules run longitudinally from the apical region to the basal region intersecting with each other. In addition, intense labelling with tubulin antibodies was observed in the apical part of the cell. The ultrastructural examinations showed that microtubules often run along the apical plasma membrane. Dot-like labelling with anti-tubulin antibodies was often observed in the perinuclear space, but not microtubules were recognized in the nucleus. Microfilaments bound to rhodamine-phalloidin were distributed mainly beneath the apical plasma membrane, and the portion along the basolateral membrane was scarcely positive. The apical pole of the follicle cell was also decorated by anti-microtubule-associated protein-2 (MAP-2). After TSH stimulation, the intensity of immunocytochemical staining against tubulin was remarkably increased in the cytoplasm. Simultaneously, at the apical region, the staining intensity of rhodamine-phalloidin was increased. Microtubules and microfilaments appeared in the pseudopods after TSH injection. In hypophysectomized or aged rats, thyroid follicular epithelial cells decreased in height, and both immunofluorescent labelling against tubulin and rhodamine phalloidin labelling were markedly decreased. These results indicate that the distribution and polymerization of microtubules and microfilaments in thyroid follicular epithelial cells vary with the functional stage. PMID- 2323951 TI - Serotonin-like immunoreactivity in the epidermal club cells of teleost fishes. AB - The present immunocytochemical study concerns the distribution of serotonin in the epidermis of three species of teleost fish. Serotonin-like immunoreactivity was found in the club cells of Heteropneustes fossilis and Carapus acus but not in those from the sea eel Conger conger. This study is the first immunocytochemical identification of serotonin in the club cells of teleost epidermis. By comparing data from the literature (Zaccone et al. 1986, 1987, 1988) regarding the occurrence of serotonin and GRP/bombesin in the exocrine sacciform gland cells of piscine skin, it is worthy mentioning here that the serotonin contained in the club cells of the species studied may have the ability to affect the pheromonal or other possible functions of these cells. The presence of serotonin in these systems has been correlated with the capacity of the exocrine glands of fish skin to secrete, ectopically, amine messengers in contrast to those produced eutopically i.e. in the neuron-paraneuron system in some vertebrates (Fujita et al. 1988). PMID- 2323952 TI - Towards microfluorometric quantitation of polyamines in situ. Relationship between cellular polyamine concentration and fluorescence yield of the formaldehyde fluorescamine method. AB - Two different fluorescence cytochemical methods, the formaldehyde-fluorescamine (FF) method and the orthophthalaldehyde (OPT) method as well as an immunocytochemical method have been developed for the localization of spermidine and spermine. Of these three methods, the FF-method is the most easy to perform. We have studied the relationship between fluorescence intensity induced by the FF method and cellular polyamine levels measured by HPLC in MCF-7 cells and HeLa cells. The experiments were designed to obtain different cell concentrations of polyamines. Cells grown on microscope slides in Petri-dishes were partly depleted of spermidine by two days inhibition of their ornithine decarboxylase activity using alpha-difluoromethylornithine. One hr before harvest the cells were exposed to different concentrations (0-30 microM) of spermidine. Microfluorometric results and chemical determinations of spermidine and spermine were obtained from each separate slide. The cellular total polyamine (spermidine + spermine) concentration on the slides varied between 4 and 15 nmol per mg protein (MCF-7 cells) and 5 and 26 nmol per mg protein (HeLa cells) and the corresponding microfluorometric results between 60 and 115 arbitrary units (MCF-7 cells) and 80 and 160 arbitrary units (HeLa cells). Simple regression analysis showed a good linear relationship between cellular polyamine concentration and FF-fluorescence yield. The correlation coefficient for MCF-7 cells was 0.86 and for HeLa cells 0.82, significance of the correlations was p less than or equal to 0.0001. Our results add further credence to the specificity of the FF-method and indicate that the method may be useful for microfluorometric quantitation of polyamines in situ. PMID- 2323953 TI - Calcium-binding proteins 33 kDa, 35 kDa, and 65/67 kDa in normal rat and Morris hepatoma tissues. A biochemical and immunohistochemical study. AB - Polyclonal antibodies were raised against membrane-associated calcium-binding proteins (apparent molecular masses 65000 and 67000 (CBP 65/67) and 33000 and 35000 (CBP 33 and CBP 35)), which were isolated from rat liver and Morris hepatoma. Using immunoblotting, various amounts of CBP 33 and CBP 35 as well as CBP 65/67 were detected in most rat organs. Using alkaline phosphatase and monoclonal-anti-alkaline phosphatase antibodies (APAAP), all the calcium-binding proteins were detected by immunohistochemical techniques in the plasma membranes of many cells, such as vascular endothelial cells, lymphocytes, epididymal principal cells, secretory and excretory duct cells of certain exocrine glands, straight distal tubular cells of the kidney, and in the cytoplasm of muscle cells and fibres as well as nerve cells and chondrocytes, and in connective tissue elements. Immunohistochemical analysis also showed that in polarized epithelial cells, e.g., renal tubular cells, epididymal principal cells or excretory duct cells, these calcium-binding proteins are present exclusively or mostly in the luminal plasma membrane. PMID- 2323954 TI - Synaptic connections of dopamine-immunoreactive neurons in the antennal lobes of Periplaneta americana. Colocalization with GABA-like immunoreactivity. AB - Dopamine-like immunoreactivity was demonstrated histochemically in about ten local interneurons in the antennal lobe of Periplaneta americana. The somata of these neurons are within the ventrolateral group of cell bodies. Additional immunohistochemical tests revealed that the same neurons also have a GABA-like immunoreactivity. Immunohistochemical dopamine staining (preembedding) of preparations in which the antennal receptor fibers had been caused to degenerate showed that in the glomerular neuropil these antennal fibers form output synapses on dopamine-immunoreactive neurons. The latter form output synapses on unstained neuron profiles. PMID- 2323956 TI - Parameters influencing the flow cytometric analysis of DNA sensitivity to nuclease S1. AB - Some parameters that influence the analysis in situ of DNA sensitivity to digestion with nuclease S1 have been studied in isolated HeLa nuclei with flow cytometry. DNA staining with the intercalating fluorochrome propidium iodide allowed the nucleolytic activity on double-stranded (ds) DNA to be determined by monitoring the relative reduction in nuclear fluorescence intensity. Nuclei isolated in buffer at low ionic strength in order to decondense chromatin fibres, showed a lower fluorescence intensity than nuclei with native chromatin, after digestion with nuclease S1 under identical conditions. Nuclei prepared with dispersed chromatin and digested with increasing amounts of enzyme showed a decrease in fluorescence intensity that reached a limit value at about 50% of the value of undigested control samples. On the other hand, in nuclei with native chromatin, fluorescence intensity decreased only about 18%. The NaCl concentration in the reaction buffer strongly influenced the DNA sensitivity to S1 nuclease. By increasing salt molarity from 5 mM to 200 mM, the digestion of dsDNA was significantly reduced as also shown by the amount of released nucleotides from purified calf thymus DNA. The detection of DNA sensitivity to nuclease S1, as assessed by the cytometric method, was shown to be more sensitive than a biochemical technique involving hydrolysis of purines. These results indicate that both the procedure for nuclei isolation and the digestion conditions have to be carefully controlled when evaluating in situ the presence of S1-sensitive sites. PMID- 2323955 TI - Enzyme activity patterns of phosphoenolpyruvate carboxykinase, pyruvate kinase, glucose-6-phosphate-dehydrogenase and malic enzyme in human liver. AB - The distribution patterns of the enzyme activities of phosphoenolpyruvate carboxykinase, pyruvate kinase, glucose-6-phosphate-dehydrogenase and malic enzyme were determined in the liver acini of men and women by microquantitative means. The activity of PEPCK was higher in men compared to the activity in women. In both sexes no heterotopic distribution pattern was observed. PK activity of men was higher, but in both sexes no heterotopic distribution was detectable. G6PDH and ME showed relatively low activity. The distribution of G6PDH and ME activity was to some extent different in men and women. Yet their heterotopic patterns were not particularly distinct. PMID- 2323957 TI - Arrangement of cytoskeletal filaments at the equator of chicken intrafusal muscle fibers. AB - The organization of the cytoskeleton at the equator of chicken intrafusal fibers was examined with immunofluorescence light microscopy, using monoclonal antibodies against myosin heavy chains, desmin, actin and tropomyosin. Actin was localized in the cytosol and in equatorial nuclei, while myosin heavy chains, desmin and tropomyosin were only observed in the cytosol. Although all four proteins were present at the equator and at the pole, the fluorescence produced after incubation with the different antibodies varied considerably between the two regions. Staining at the pole was in the form of striations, but at the equator it was non-striated and more uniform. The observed fluorescent patterns suggest that at the equator filaments are assembled into looser arrays than in the sarcomeres of the pole. A flexible cytoskeleton at the equator would be an appropriate substrate for distorting the affixed sensory endings during an applied stress. PMID- 2323958 TI - Gastrin-cholecystokinin-like and neuroparsin-like immunoreactivities in the brain and retrocerebral neuroendocrine complex of the cockroach Blattella germanica. AB - Using single and double labelling techniques respectively, brain-corpora cardiaca corpora allata complexes of the cockroach Blattella germanica have been immunohistochemically investigated with antisera raised against either the vertebrate peptide gastrin-cholecystokinin (CCK-8(s] and/or the locust neurohormone neuroparsin (NPA). Single immunolabelling with anti-CCK-8(s) reveals immunoreactive perikarya and processes in median and lateral parts of protocerebrum, optic lobes, deutocerebrum and tritocerebrum. Some fibres originating in median and lateral protocerebrum are intrinsic to the brain, whereas others terminate in the nervous areas of the corpora cardiaca. Single immunolabelling with anti-NPA reveals immunoreactive cell bodies in the median part of the protocerebrum and their processes terminate both in the nervous area of the corpora cardiaca and between the intrinsic secretory cells of this neurohaemal organ. Double immunolabelling with anti-CCK-8(s) and anti-NPA enables a description of the anatomical relations between the processes and the endings of these two neurosecretory systems. PMID- 2323959 TI - Ultrastructural localization of acid phosphatase in spermatic cells of Ceratitis capitata (Diptera). AB - The cytochemical study of acid phosphatase in spermatic cells of Ceratitis capitata defines the enzimatically active sites, relating this enzyme with morphological modifications of the cell components during spermiogenesis. In the axoneme, acid phosphatase is associated with the metabolism of phosphates which promote flagellar motility. The enzymatic activity verified on the cytoplasmic membranes demonstrates the importance of this enzyme in the process of cellular differentiation. PMID- 2323960 TI - Effect of different fixatives on Con A surface receptors of mouse peritoneal macrophages. AB - The effects of glutaraldehyde, formaldehyde, or osmium tetroxide fixation on the number of labeled Con A surface receptors on mouse peritoneal macrophages were compared. Gold-labeled Con A receptors were found to be isolatedly arranged and evenly distributed on cell surfaces independent of the fixative used. Only cells preincubated with Con A and subsequently fixed by osmium tetroxide showed arrangement of labeled receptors in clusters. Significant differences were found in the number of Con A receptors per cell depending on the fixative used. The fluorescence intensity of FITC-Con A staining was detected spectrophotometrically, the characteristic X-rays of gold-labeled Con A receptors were determined by means of electron beam-induced X-ray microanalysis. The experimental results obtained both at light and electron microscopic level pointed to formaldehyde being the best fixative also for this purpose. PMID- 2323961 TI - Job-stress and medical consultation rates for physical illness among blue collar workers of an electrical factory in Japan: a four-year prospective follow-up study. AB - To investigate the relationship between job-stress and medical consultation rates for physical illness, a prospective study was conducted for male blue workers of an electrical factory in Japan. 8 job-stress variables and 8 possible confounders were assessed by means of mailed questionnaires in the initial study; 375 workers without medical history of illness were followed for four years; they were interviewed once a year and medical consultations for physical illness were recorded. Age-adjusted rates of medical consultation during the four-year period were significantly higher in the subjects with higher job-dissatisfaction scores than in those with lower job-dissatisfaction scores (p less than 0.05). The results of the multiple logistic regression analysis indicated that job dissatisfaction together with age and education was significantly correlated with medical consultation (p less than 0.05). The results suggest that job dissatisfaction is a potential factor for medical consultation in Japanese blue collar workers. PMID- 2323962 TI - Comparison of urinary delta-aminolevulinic acid excretion and erythrocyte delta aminolevulinic acid dehydratase inhibition in different strains of mice exposed to lead. PMID- 2323963 TI - Noise surveys in discotheques in Hong Kong. PMID- 2323964 TI - Synergism of ascorbic acid and glutathione in the reduction of hexavalent chromium in vitro. AB - The reduction of 20 microM hexavalent chromium [chromium(VI)] in single-reductant solutions of 0.02-2 mM L-ascorbic acid (L-AsA) or 2 mM reduced glutathione (GSH), and in mixed solutions of 2 mM GSH containing L-AsA of the above-described concentrations was investigated at physiological pH (37 degrees C). The reduction of chromium(VI) in the L-AsA solutions of higher concentrations showed pseudo first-order kinetics in a single phase with respect to chromium(VI). In the lower L-AsA concentrations, pseudo-first-order processes appeared only in an early stage of the reaction. The reduction in the GSH solution was characterized by a two-phase process. In the first phase, which appeared in very short duration, the reaction rate was much higher than that in the second, but resulted in a decrease of only 7% of the initial chromium(VI) level. The second phase showed the main process of the reduction. This indicated pseudo-first-order kinetics. The half life values of chromium(VI) depended on the initial levels of the reductants and ranged from seconds to hours. The chromium(VI)-reducing ability of L-AsA was markedly higher than that of GSH. In the mixed solutions of L-AsA and GSH, synergistic effect on the reduction of chromium(VI) was observed, especially in earlier stages of the processes. The synergism was more conspicuous in the mixed solutions containing lower L-AsA levels. These results suggest that although AsA possesses higher reducing ability than GSH, their coexistence is of importance for the reduction of chromium(VI) in biological systems because of their synergism. PMID- 2323965 TI - The treatment and long-term prognosis of children with intracranial tumors: a study of 610 cases, 1950-1981. AB - Six hundred and ten children aged under 16 years with intracranial tumors were referred for radiotherapy between 1950 and 1981: 579 were new cases and 31 had recurrent disease after primary treatment elsewhere. Radiotherapy was completed in 93% of all cases. The actuarial survival rate for all new cases was 53% at 5 years, 46% at 10 years, 40% at 20 years, and 39% at 30 years. The oldest children (10-15 years) had the best survival and the youngest (0-2 years) had the worst survival. Children treated with megavoltage x-ray equipment (1970 to 1981) had a significantly greater survival than those treated with orthovoltage X rays (1950 1969). Overall, a direct correlation was found between survival and maximum radiotherapy dose. Children having a total excision of the tumor prior to radiotherapy showed a greater survival than those treated by a subtotal or partial tumor removal. Children treated by radiotherapy alone had a survival comparable to those treated by sub-total excision and radiotherapy. There is a striking difference in survival expectation depending on initial functional category (I to III). The overall survival rates of 428 children completing treatment for glioma were 49% at 5 years, 43% at 10 years, and 40% at 15 years. The results according to certain specific tumor sites within the cerebral hemispheres are reported. Age is an important prognostic factor in low grade and also high grade astrocytomas, children having longer survivals than adults. Sub total or partial excision of craniopharyngiomas combined with radical radiotherapy appears to give the best long-term results. Of 73 new cases, the 5-, 10-, and and 15-year survival rates were 92%, 84%, and 79%. Recurrent craniopharyngiomas treated by surgery alone can be salvaged by further conservative surgery and radical radiotherapy. Optic gliomas are slow growing low grade astrocytomas. Survival rates at 5, 10, and 15 years for 20 children with mostly chiasmal lesions were 89%, 89%, and 78%, respectively. In 73 children with brain stem tumors, 17% remained alive for up to 15 years. The risk of CNS seeding from intracranial ependymomas depends on site of origin and grade of malignancy, with 50% incidence occurring in cases with high grade lesions situated in the posterior fossa. Survivals at 5, 10, and 15 years in 51 children were 51%, 40%, and 31%. Adjuvant chemotherapy improves survival.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2323966 TI - Long-term psychological effects in children treated for intracranial tumors. AB - The results are reported of the psychological assessment of 62 children who presented with primary intracranial tumors and who received radiotherapy at the Royal Marsden Hospital between 1963 and 1973. Evaluations were carried out 3-20 years after treatment. All patients were free from progressive tumor at testing. The average IQ of the total series was within the normal range (Full-Scale IQ 92) but 23% of the patients were functioning at an educationally subnormal level of intelligence (IQ less than 80). Sex, tumor type, tumor location and the radiotherapy volume and site of maximum dose were not found to have a significant effect on intellectual outcome. A significant correlation was found between intelligence and age at the time of treatment. Children who received treatment under the age of 5 years were more adversely affected (average IQ 72) than those who were aged 6-10 (average IQ 93) and those aged 11-15 years (average IQ 107). The incidence of neurological abnormalities and physical disability was significantly greater among patients with supratentorial tumors (72% of cases), compared with patients with infratentorial lesions (44% of cases). The results were discussed in terms of the management of young patients with intracranial tumors. PMID- 2323967 TI - Medulloblastoma in adults: a review of 47 patients treated between 1952 and 1981. AB - The results of treatment of 47 adults with medulloblastoma are reviewed. For those treated with ortho-voltage radiotherapy between 1952 and 1963 the actuarial 5- and 10-year survival rates were 38% and 23%, respectively. Of those treated with megavoltage radiotherapy between 1964 and 1981, the corresponding 5- and 10 year survival rates were 59% and 53%, respectively. Of patients treated with megavoltage radiotherapy and adjuvant chemotherapy between 1971 and 1981, 76% were alive at 5 years and also at 10 years. Treatment factors associated with an increased survival were complete or subtotal resection of the primary tumor, as opposed to partial removal, a radiation dose to the posterior fossa of 55 Gy or more and the administration of adjuvant chemotherapy. Neither the quality of life, nor the fertility of the surviving patients, have been impaired by the treatment. Six patients (13%) developed metastatic disease outside the central nervous system. PMID- 2323968 TI - Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962-1987. AB - A retrospective analysis has been made of all patients with pineal and CNS germ cell tumors who were treated at The Royal Marsden Hospital between 1962-1987. A total of 67 new cases were seen: 17 had initial histological verification of tumor type and the remainder were tested for radiosensitivity with a dose of 20 Gy following a shunting procedure. Patients with germ cell or radiosensitive tumors were treated with a uniform policy of whole neuraxis radiotherapy giving 50 Gy to the local tumor and 30 Gy to the remaining brain and spinal cord. Nonresponding lesions continued with local fields to a dose of 50 Gy. Patients were divided into three groups (a) germinoma and radiosensitive tumours, 34 cases; (b) malignant teratoma, 12 cases; (c) non-germ cell, 21 cases. Median follow-up is 83 months (range 2-246 months). Overall and cause specific actuarial 5/10 year survival were for group 1, 81.7%/69.4% and 86.5%;/86.5%; group 2, 18.2%/18.2% and 18.2%/18.2%, and group 3, 64.3%/46.8% and 64.3%/52.6%, respectively. No patient in group 1 treated during the last 12 years has recurred. Univariate analysis of factors at presentation, showed that neurological performance status (p less than .001) as well as tumor type (p less than .001) correlated with outcome. Recurrence was confined to the primary site in only 1 of 4 patients in group 1 compared to 6 of 9 patients in group 2 and 9 of 10 patients in group 3. No isolated spinal recurrence occurred in group 1 patients. A total of eight patients have received platinum containing chemotherapy for recurrence (6 cases) or adjuvant therapy (4 cases). Germinomas appear to respond better than teratomas, all of which have recurred rapidly following initial partial response. Shunting and radiosensitivity testing remains the treatment of choice for tumors compatible with germinoma. Craniospinal irradiation is associated with low morbidity providing spinal growth is complete and is recommended in older patients as salvage following spinal recurrence is unsatisfactory. Aggressive combined modality approaches with surgery, radiotherapy and chemotherapy need to be investigated to improve results in CNS teratoma. PMID- 2323969 TI - Low grade glioma of the cerebral hemispheres in adults: a retrospective analysis of 88 cases. AB - Eighty-eight adult patients with histologically verified cerebral low grade gliomas (grades 1 and 2) treated with post-operative radiotherapy at the Royal Marsden Hospital between 1960 and 1985 were reviewed. Survival of oligodendroglioma patients was greater than those with astrocytoma (64% vs 36% at 5 years) but the difference was less marked in the long term (35% vs 26% at 10 years). Previous studies have identified prognostic factors important in these tumors: age, extent of surgery, grade, performance status, and duration of symptoms. In this study of low grade astrocytomas and oligodendrogliomas, age (highly significant in the former and significant in the latter), extent of surgery (oligodendrogliomas), and performance status have been demonstrated as factors influencing outcome. The precise role of radiotherapy including the optimal radiation dose and timing of treatment remains unclear. The information, given by a retrospective analysis such as this, helps in the design of prospective, randomized studies looking at radiation dose and time of surgical and radiotherapeutic interventions, always with careful assessment needed of quality of life and treatment morbidity. PMID- 2323970 TI - Childhood cerebellar astrocytomas: is there a role for postoperative irradiation? AB - Eighty children with astrocytomas of the cerebellum were treated at Washington University Medical Center in St. Louis, Missouri from 1928-1980. The most important predictor of recurrence was completeness of surgical removal. Of 40 patients whose tumors were totally removed, only one recurred (2.5%). Forty cases were subtotally removed and 14 subsequently recurred (35%). Postoperative irradiation did not significantly improve survival in the patients with incompletely excised tumors; however, there was lack of uniformity in the radiation therapy. Although a survival advantage could not be demonstrated, there was a trend toward a lowering of the recurrence rates in patients with subtotally excised solid tumors who received radiation therapy. PMID- 2323971 TI - Radiation therapy for head and neck cancers in the elderly. AB - Three hundred and thirty-one patients, aged more than 70 years, were treated for an upper aerodigestive tract carcinoma from 1978 to 1983. Larynx accounted for 28% of the primary sites, oropharynx for 27%, and the oral cavity for 16%. One third of these patients had a contraindication to anesthesia. The treatment was consistent with our protocols in only half of the cases. Fifty-nine patients underwent a radiosurgical combination; 249 underwent an exclusive irradiation with a curative intent. Fifty-four patients underwent a palliative irradiation, which lead up to a "curative dose" in half of the cases. The immediate and long term tolerance of the irradiation was good. The local control was 71% for patients treated with a curative intent and 19% for the palliatively irradiated patients. Five-year survival of the population was 33%. No significant relationship between age, general status, and the carcinologic outcome could be observed. PMID- 2323972 TI - The prevalence and severity of late effects in normal rat duodenum following intraoperative irradiation. AB - In humans, a portion of the duodenum is often at risk for radiation-induced complications following intraoperative radiation therapy for pancreatic carcinoma. To determine experimentally the prevalence and severity of late effects in the normal mammalian duodenum, 190 rats received single doses of 0, 15, 20, 25, 30, or 40 Gy orthovoltage X rays to temporarily exteriorized 3 cm circumferential segments of duodenum. The animals were killed 2, 6, 8, or 10 months later. Actuarial survival, change in body weight, and a radiation injury score based on eight histopathologic alterations were used as endpoints. Epithelial atypia, intestinal wall fibrosis, serosal thickening, and vascular sclerosis were the dominant histopathologic alterations at all dose levels throughout the 10-month observation period. The prevalence and severity of histologic radiation injury showed sigmoidal dose-response relationships with the plateaus starting at 20 Gy. Doses of 20 Gy or greater also resulted in a substantial loss of body weight and a high level of early deaths (20-80 days). All endpoints indicate that intraoperative doses of 20 Gy or greater are associated with unacceptable risks of late and irreversible complications. PMID- 2323973 TI - The use of postoperative irradiation for the prevention of heterotopic bone after total hip replacement with biologic fixation (porous coated) prosthesis: an animal model. AB - Radiation has been shown to be effective in the prevention of heterotopic bone. The exact etiology of heterotopic bone is unknown. Total Hip prosthetic devices that do not depend upon bone cement for fixation have become increasingly popular. The mechanism by which the bone forms around the prosthesis is similar to the process by which fractures heal which has been shown to be sensitive to irradiation. Using a rabbit model we have undertaken a study to investigate the effect of irradiation on the bony ingrowth on porous coated implants. Forty-five rabbits had porous coated implants surgically placed in the tibiae bilaterally. Each rabbit had one tibae randomly irradiated with 1,000 cGy in 5 fractions starting on the first post-operative day. Animals were sacrificed weekly starting 2 weeks post-operatively and the tibae were sent for pullout studies. The amount of force necessary to pullout the treated tibae was statistically less than the amount of force necessary to remove the untreated tibae at 2 weeks. From 3 weeks on there was no difference in the force necessary to remove the prosthesis from the untreated or treated tibae. Histologically, the untreated tibae showed bone formation while the treated tibae did not. Because of these results, it is suggested that the treatment of patients at risk for development of heterotopic bone be modified to only include the area between the femur and pelvis avoiding treatment of the prosthetic device. PMID- 2323974 TI - Fractionation sensitivity and immunological status in radiation treated murine sarcomas. AB - The fractionation sensitivity of a strongly immunogenic murine fibrosarcoma (FSa1) was tested in highly immunosuppressed (18 Gy whole body irradiation, 10 fractions, 4 days and bone marrow salvage) and control mice (C3Hf/Sed). Radiation was delivered to extremity-transplanted tumors after reaching a volume of 250 mm3. Two, 4 and 10 fractions were used, delivering the radiation treatments to uniformly hypoxic tumors (by extremity clamping). Doses needed to attain a 10 day tumor-growth delay (TGD) over the volume range 250 mm3 to 1000 mm3, and doses necessary to reach a tumor-control probability of 50% (TCD50), were calculated for the three fractionation schedules. Immunosuppression influenced the TCD50 values profoundly: 56.2, 71.5, and 101.4 Gy in control mice versus 76.6, 104.2, and 141.1 Gy in immunosuppressed mice for 2, 4, and 10 fractions, respectively. The alpha/beta ratios estimated by reciprocal-dose analysis using the TGD and TCD50 assays were not significantly different, nor were the alpha/beta ratios of tumors grown in immunosuppressed mice (TGD 5.7 Gy; TCD50 5.3 Gy) as compared with tumors in control recipients (TGD 3.5 Gy; TCD50 4.9 Gy). In addition, direct analysis was used with the fractionated TCD50 data from control and immunosuppressed animals to calculate a immunity-related-cell-kill factor. For 250 mm3 tumors a 1.29 [0.99 . . . 1.59, 95% confidence interval] log10-kill factor was obtained. PMID- 2323975 TI - Enhancement of radiation damage in cellular DNA following unifilar substitution with iododeoxyuridine. AB - The exact mechanism of x-ray radiosensitization with iododeoxyuridine (IdUrd) is not known. Using log phase V79 cells, we compared radiosensitization following unifilar (9 hr exposure) and bifilar (17 hr exposure) substitution with 10(-5) M IdUrd. The % thymidine replacement was 8% and 16%, respectively. Significant radiosensitization was found with unifilar (Do = 1.35 Gy, n = 5.8) and bifilar substitution (Do = 1.2 Gy, n = 4.0) compared to controls (Do = 1.7 Gy, n = 8.5). Using filter elution techniques, the enhancement ratios (ER) for double strand breaks (SB) were 1.5 and 2.0 for unifilar and bifilar substitution, respectively, whereas the enhancement ratio for single strand breaks were both greater than or equal to 2.1. Comparing the enhancement ratios with unifilar substitution for single strand breaks in substituted (2.4) and unsubstituted complement strands (1.9) as well as in unsubstituted duplex DNA (1.4) in cells containing IdUrd substituted DNA, there was increased damage in unsubstituted strands compared to irradiated controls. These data suggest that in vitro radiosensitization following unifilar substitution with IdUrd results, in part, from damage to unsubstituted complementary strand and adjacent doubly unsubstituted DNA. The radiolysis of halogenated DNA produces mobile reactive intermediates which may cause intermolecular DNA damage such as single strand breaks in unsubstituted DNA and resultant double strand breaks and this damage is probably responsible for increased lethality after x-irradiation. PMID- 2323976 TI - Radiotherapy of the rhabdomyosarcoma R1H of the rat: postoperative radiotherapy. AB - Rhabdomyosarcoma R1H of the rat was excised aiming for a complete macroscopic local excision. Adjuvant radiotherapy was performed from the third postoperative day on. Former tumor sites were locally irradiated with 200 kVp X rays 4 times per week over a period of 6 weeks. Total doses of 0, 15, 30, 45 and 60 Gy were applied. The tumor volume was measured and the time to regrow to initial volume was assessed. The results were compared to the effect of a standard radiotherapy alone with 30 fractions of 2 Gy applied within 6 weeks. All tumors recurred despite of the irradiation treatment. At high total doses (greater than 30 Gy), adjuvant radiotherapy was found to improve short term tumor response considerably, whereas no positive effect was seen at low doses. After a total dose of 60 Gy and long time intervals after start of treatment, radiotherapy alone and a combination of surgery and radiotherapy seem to be isoeffective in our tumor system. PMID- 2323977 TI - Large scale optimization of beam weights under dose-volume restrictions. AB - The problem of choosing weights for beams in a multifield plan which maximizes tumor dose under conditions that recognize the volume dependence of organ tolerance to radiation is considered, and its solution described. Structures are modelled as collections of discrete points, and the weighting problem described as a combinatorial linear program (LP). The combinatorial LP is solved as a mixed 0/1 integer program with appropriate restrictions on normal tissue dose. The method is illustrated through the assignment of weights to a set of 10 beams incident on a pelvic target. Dose-volume restrictions are placed on surrounding bowel, bladder, and rectum, and a limit placed on tumor dose inhomogeneity. Different tolerance restrictions are examined, so that the sensitivity of the target dose to changes in the normal tissue constraints may be explored. It is shown that the distributions obtained satisfy the posed constraints. The technique permits formal solution of the optimization problem, in a time short enough to meet the needs of treatment planners. PMID- 2323978 TI - Evaluation and optimization of the electromagnetic performance of interstitial antennas for hyperthermia. AB - Effective and realistic evaluation of the performance of interstitial antennas for microwave hyperthermia involves: (a) calculations of the radiation characteristics of these antennas, including those of multi-section designs, and (b) the development of 3-dimensional models of tumors and the computation of the power deposition patterns in these tumors due to their irradiation by an array of interstitial antennas. In this paper, we address both of these issues. Specifically, we developed numerical models for calculating the radiation characteristics of multi-section insulated antennas, and we utilized a 3 dimensional model based on a volume integral equation formulation for calculating the power deposition pattern in tumors. Numerical results were verified by comparing them with experimental data available in the literature. New numerical data are presented to illustrate the advantages of multi-section designs over uniformly-insulated interstitial antennas and to show the feasibility of using amplitude and phase steering capabilities to control the power deposition patterns of an interstitial antenna array. The role of each section in a multi section antenna design in guiding versus radiating the electromagnetic energy and hence in controlling the power deposition pattern of multi-section antennas is also described. PMID- 2323979 TI - Radiation therapy for gliomas of the optic nerve and chiasm. AB - Thirty-three patients with optic glioma seen over a 30-year period were reviewed. Five patients (15%) had tumor confined to the optic nerve, 8 patients (24%) had optic nerve and chiasmal involvement, and the remaining 20 patients (61%) had invasion of contiguous structures as well as chiasmal involvement. Eleven patients (33%) had a history of neurofibromatosis. Two-thirds of the patients had either a biopsy or a partial resection of the tumor, with the remaining one-third being clinically diagnosed. All patients received irradiation to local fields. The median dose was 5040 cGy in 160 cGy fractions. Of patients alive at last follow-up, the median time of follow-up was 12.3 years. The 5-, 10-, and 15-year overall actuarial survivals were 94, 81, and 74%, respectively. Univariate and multivariate analysis were performed on the following clinical variables: extent of primary tumor, extent of surgery, dose of radiation, gender, race, age, and presence or absence of neurofibromatosis. Extension of the primary lesion to the optic chiasm and age less than or equal to 15 years were the only two variables to have statistically significantly inferior 15-year progression free survivals by multivariate analysis. Eighteen (55%) patients had treatment related complications with most involving the pituitary gland. We conclude that postoperative radiotherapy is beneficial in patients with chiasmal involvement and those with incomplete resections. A minimum tumor dose of 4000 cGy is recommended. PMID- 2323980 TI - Effects of pH on heat sensitization of mammalian cells with procaine hydrochloride. AB - The enhancement of heat killing of CHO cells by treatment with 7 mM procaine HCl increased when cells were treated under alkaline conditions. Below a pH of 6.9, very little heat sensitization was observed; however, as the pH was increased to 7.4 and above, considerable heat sensitization occurred. There were no changes in intracellular pH at the beginning of heating that could be responsible for this phenomenon. PMID- 2323981 TI - An interactive system for point dose optimization. AB - An interactive system has been developed to aid in determining optimal photon and electron beams and beam weights for radiotherapy treatment planning. Dose constraints at various points are selected and an algorithm searches for a set of beams and weighting factors that satisfy these constraints. In the event that no combination of beam weights satisfies the choice of treatment modalities and dose constraints, the treatment modalities and dose constraints can be modified interactively. The goal of this procedure is different from that of more conventional optimization schemes in which optimal dose values are specified and the optimization algorithm determines the set of beam weights that yields a dose distribution closest to optimal. PMID- 2323982 TI - Dosimetric analysis in brachytherapy of carcinoma of the cervix. AB - Brachytherapy plays an essential role in the definitive radiation treatment of cervical carcinoma. The dosimetry of intracavitary irradiation is complex in that the optimum doses that can be delivered are dictated not only by the volume and extent of tumor but also by the close vicinity of dose-limiting structures, such as the small and large intestines, rectum, and bladder. To facilitate understanding of the relationships between the various dosimetric parameters involved, a retrospective analysis of 50 randomly chosen intracavitary insertions with Cesium-137 in 41 patients performed at our institution between 1975 and 1985 was carried out. All 50 cases utilized Fletcher-Suit-Delcos applicators and only the insertions using three sources in the tandem and one in each of the ovoids were included in this analysis. Using the AP and lateral radiographs and the lymphatic trapezoid, the reference points were obtained and transferred digitally to the treatment planning computer, and computerized dosimetry performed. In addition to the specified reference points, points were added and modified to obtain more complete information. The doses at the specified points were normalized to the average dose at AT, a reference point 2 cm superior to external os and 2 cm lateral to the tandem, and expressed as a percentage. It was noted that the average dose at the closest bladder point was 103 +/- 41% of the dose at AT, the maximum rectal dose 77 +/- 29% of the dose at AT and the maximum small bowel dose 65 +/- 16% of that at AT. The analysis of percent contribution of various sources to different reference points revealed that the dose to point AT was equally contributed to by all sources; bladder and rectal doses were mainly contributed to by the lowermost uterine and ovoid sources. Our analysis may provide a model for optimizing brachytherapy in cervical carcinoma. PMID- 2323983 TI - Management of childhood cerebellar astrocytoma. PMID- 2323984 TI - Volume effects. PMID- 2323985 TI - [Scholarship report on quality assurance in the USA]. PMID- 2323986 TI - [Scholarship report. Midwife in Chile]. PMID- 2323987 TI - The effect of macromolecular rat serum fractions on conceptuses cultured in human serum: role of transferrin. AB - We describe the results of experiments to study the effects on rat conceptuses cultured in human serum supplemented with rat serum which was separated into high (greater than 30 kDa) and low (less than 30 kDa) molecular weight fractions by ultrafiltration. Ultrafiltered rat serum was found to lack certain growth promoting substances which are necessary for embryonic growth and differentiation during the culture period. Culture in whole human serum or human serum supplemented with low molecular weight fraction (filtrate) results in conceptuses which grow reasonably well but are anaemic, whilst anaemia is relieved by the high molecular weight fraction. Addition of human or rat transferrin (MW 80 kD approx.) to whole human serum alleviates anaemia, an effect observed more distinctly with rat transferrin. PMID- 2323988 TI - Branching pattern of the motor nerve endings in a skeletal muscle of the adult rat. AB - We have performed a morphometric analysis of the branching pattern of the rat sternomastoid motor nerve terminals in normal and regenerated singly-innervated synaptic areas, in junctions with an accessory ending and also in dually innervated synaptic areas. We tried to seek measurable differences related to the terminal complexity and size in these different situations. The number of sole plate nuclei is always significantly correlated with the nerve terminal parameters and unrelated to the muscle cell diameter. A significant correlation between the terminal complexity and the postsynaptic size is found only in the smallest endings whereas correlation is lost with the increase in nerve terminal complexity. In normal singly-innervated areas, the mean length of the distal free end segments of the terminal arborisation becomes reduced with the increase in complexity of the terminals, whereas the mean length of the segments between branching points and the mean angle of branch emergence is, on average, constant. Whereas the accessory endings show the same branching pattern as the endings during the initial days of regeneration, the parent ending can be considered as a miniature version of the endings in normal singly-innervated junctions. In dually innervated areas, the smallest endings show a similar branching pattern to the accessory endings and the endings during the initial process of reinnervation, whereas the larger endings show a significant reduction in the length of the distally placed segments compared to the normal endings in singly-innervated areas. Results indicate that the terminal branching pattern is not haphazard but, on the contrary, general rules and tendencies can be measured. PMID- 2323989 TI - Prolactin receptors in the primate choroid plexus. AB - The presence of prolactin receptors in the choroid plexus of primates has until now been assumed to be based on observations made on lower vertebrate animal models. An in vitro autoradiographic technique employing the principles of competitive binding was used to demonstrate the presence of specific prolactin binding sites in the choroid plexus of monkeys. Thus the primate choroid plexus resembles that of lower vertebrate mammals in that it possesses the prerequisite receptor for a prolactin blood-to-CSF transport mechanism. PMID- 2323990 TI - The megachiropteran pineal organ: a comparative morphological and volumetric investigation with special emphasis on the remarkably large pineal of Dobsonia praedatrix. AB - This investigation is based upon the pineal organs of 92 specimens of 36 species of the family Pteropodidae (Mammalia, Chiroptera). The size of the megachiropteran pineal correlates well with body size (r = 0.864), confirming the former conclusions that generally larger bodied bats have larger pineals. The range of the pineal size index in 36 megachiropteran species is from 33 to 4393. In most species the pineal organs are small, deeply recessed under the cerebral hemispheres and of Type A (except in Dobsonia and Pteropus, where they are of Type alpha beta C and AB, respectively). Morphological and volumetric data gathered from serially sectioned brains include body and brain weights, pineal type, dimensions, volume and size index for each species. There are distinct dorsal and ventral subdivisions of the pineal in some species and a clear separation of pineal parenchyma into cortical and medullary regions in others. In several species where overlying ependyma is lacking pinealocyte clusters communicate freely with the CSF. Groups of intrapineal neurons are noted in the connective tissue beside blood vessels. The habenular commissure shows much interspecific variation in its course through the pineal. Detailed examination of pineal-brain relationships clearly suggests that, due to the generally deep location of the pineal in relation to cerebral hemispheres, pinealectomies in the species studied may be extremely difficult, it not entirely impossible. The absolutely and relatively largest pineal organ among bats, and relatively perhaps among all vertebrates, has been discovered in the New Guinean naked-backed bat, Dobsonia praedatrix, with pineal size index of 4393, and a volume of 16.3447 mm3, which is 0.56% of the brain. This alpha beta C-type, mushroom-shaped, solid and compact pineal organ measures 5.33 x 4.51 mm. The cortical and medullary parenchyma are divided into lobes by large calibre blood vessels along which numerous intrapineal neurons are observed. A smaller but similarly shaped pineal is noted in the other three Dobsonia. Data on the largest known pineals in ratitae birds, seals and walruses have been compared with that of D. praedatrix and the human pineal. This study supports the hypothesis that pineal development may reflect dependence on habitat and possibly other related factors. PMID- 2323991 TI - Variation in the response of chick embryos to incision of the roof plate of the neural tube at different developmental stages. AB - The effects of microsurgical reopening of the neural tube were examined in chick embryos of Stages 12-18. The roof plate of the thoracic neural tube was incised for a length equivalent to 7 somites. The site of incision was studied histologically and by SEM and TEM at intervals up to 48 hours. 48 hours after operation, persistent neural tube defects were more frequent and longer in embryos of more advanced stages at operation. Exposure of embryos to Streptomyces hyaluronidase, which inhibits neurulation in normal embryos, has no effect on the healing of the incised neural tube in the young embryos. Healing of the lesion in younger embryos appeared to occur in two stages: initially, by repair of the surface ectoderm, by a cephalo-caudal zipper-like mechanism, followed by a reconstitution of the roof plate by migration of neurectodermal cells on the deep surface of the ectoderm. Neural tubes of older embryos splay open more widely on incision of the roof plate, apparently making healing mechanically more difficult. This wider splaying may be related to the decline of forces which maintain occlusion of the neural canal in younger embryos. PMID- 2323992 TI - Regulation of haematopoietic stem cell proliferation by stimulatory factors produced by murine fetal and adult liver. AB - Haematopoietic stem cells in murine fetal liver are in a proliferative state unlike those in normal bone marrow which are quiescent. A regulatory activity is produced by cells in the fetal liver which will switch quiescent normal bone marrow haematopoietic stem cells into cell cycle in vitro. This regulator from Day 15 fetal liver cells is produced by adherent cells and by cells fractionated on a Percoll gradient in the 1.064 and 1.076 g per cm3 density bands but not in the 1.123 g per cm3 band. Colony-stimulating factor cannot be detected in the supernatants containing the stem cell regulatory activity. The stimulator can be detected in supernatants produced from cell suspensions of liver cells at Day 15 and Day 17 of gestation and 24 hours and 72 hours after birth. However by 1 week after birth the production of the stimulator decreases and is undetectable 3 and 10 weeks after birth. The total numbers of haematopoietic stem cells (CFU-S) in fetal liver decrease from Day 15 of gestation and only small numbers are present 1 week after birth. Thus the decline in the production of haematopoietic stem cell proliferation stimulator correlates with the decrease in haematopoietic stem cell numbers in the liver through gestation and after birth. PMID- 2323993 TI - The peripolar cell: a distinctive cell type in the mammalian glomerulus. Morphological evidence from a study of sheep. AB - We used scanning electron microscopy to study the glomerular peripolar cell in the kidneys of seven sheep. Peripolar cells were present in a variable proportion (3.6-100%) of glomeruli. Although on average two peripolar cells were present at each vascular pole, up to ten were seen on occasion. They were more often related to the afferent than to the efferent arteriole. Mapping the relative position of each cell failed to reveal any zonal distribution in the renal cortex. Scanning electron microscopy showed that they were globular in shape and had a bossellated surface. We showed by examination of cells which had been broken open that this appearance was due to the presence of cytoplasmic granules that produced bulging of the cell membrane. We suggest that scanning electron microscopy is a suitable method for studying this cell in the mammalian kidney. PMID- 2323994 TI - Arterial supply to the lumbar lymph nodes in man. AB - The arteries supplying the lumbar lymph nodes were investigated in 39 cadavers. In the upper region (L2), a branch of the testicular or ovarian artery predominated and supplied the right and left para-aortic nodes. In the middle region (L3), unpaired slender vessels originated directly from the aorta above or below the inferior mesenteric artery and passed to the pre-aortic and, rarely, the right para-aortic nodes. In the lower region (L4), tiny vessels passed from the ventrolateral and/or lateral part of the aorta to the lower para-aortic, pre caval and lateral caval nodes and, further, gave off twigs to the ureter and muscles. The slender branches which originated from the abdominal aorta showed a segmental pattern, though incomplete, and it is suggested that these remnants are vestiges of ventral and lateral segmental arteries in the young embryo. PMID- 2323995 TI - Morphological variations of the human vastus lateralis muscle. AB - Variations in the gross morphology of quadriceps femoris were assessed in 40 cadavers. An additional (fifth) head was present in about one third of the limbs. Distally, fusion between vastus lateralis and vastus intermedius varied from almost complete fusion to less than one third of the interface between the muscles. Discrete tendinous laminae arising from vastus lateralis were present in 29% of the limbs. In half the cadavers there were differences in quadriceps topography on right and left sides but there were no significant differences between muscles from male and female subjects. These findings may have important implications in clinical and microscopic studies of the quadriceps muscle. PMID- 2323996 TI - Looping of chick embryo hearts in vitro. AB - Heart rudiments were removed from chick embryos at times earlier than any previously reported, and cultured in vitro, in order to test the widely reported view that looping is an intrinsic process. This view is based on experiments that are inadequately reported in certain key details. An organ culture technique was employed which combined ease of observation with good nutrient and mechanical support for the explants. A total of 23 hearts from stages before the onset of looping were examined. Hearts from as early as the six-somite stage looped normally in these experimental conditions. The view that heart looping is an intrinsic phenomenon is therefore confirmed. PMID- 2323997 TI - The human vertebral column at the end of the embryonic period proper. 3. The thoracicolumbar region. AB - The present study of the thoracicolumbar region continues an investigation of the vertebral column at 8 postovulartory weeks (the end of the embryonic period proper) by means of graphic reconstructions. The cartilaginous vertebrae have short neural processes associated with the normal spina bifida occulta present at this time. The separate cartilaginous centres that several authors believe to exist in the cervical and lumbar costal elements, but which have not been observed by the present authors, have been thought to be the forerunners of extrathoracic ribs. A distinction needs to be made, however, between such centres and ribs. Similarly, in the fetal period, ossific loci in the costal elements of CV 7 are very frequent, whereas cervical ribs in the adult are relatively rare. The neurocentral joints, and hence the boundaries between neural arches and centra, are unclear before ossification has begun and has progressed during the fetal period. The sternal bands are almost completely united and the scapula is high in position. Neural relationships aid in the determination of homologous parts within the vertebral column, but clarification of corresponding parts has not previously been possible within the embryonic period. Areas ventral to the dorsal rami are ribs in the thoracic region and costal elements in other regions. Areas underlying the dorsal rami are transverse processes in the thoracic region and minute 'true' transverse elements in the cervical and lumbar regions. Thus, the descriptive lumbar transverse processes correspond to the true transverse processes and the ribs in the thoracic region. The dorsal rami of the thoracic nerves pass between the transverse processes and the tubercles of the ribs and then divide. The ventral rami of lumbar Nerves 1 and 2 resemble the thoracic in their course, whereas those of Nerves 3-5 are similar to the sacral. The thoracic dorsal roots are sloping and, associated with the greater height of the lumbar centra, the lumbar roots even more so. The directions of the various dorsal roots reflect differences in growth gradients between vertebral column and spinal cord. The thoracic and lumbar portions of the column change little in proportion during the embryonic period proper. PMID- 2323998 TI - Onset of spermatozoal degeneration in low-fertility Delaware roosters and test for autoimmune basis. AB - The objectives of this study were 1) to determine the onset of a heritable reproductive disorder in the rooster that is characterized by extensive spermatozoal degeneration within the ductus deferens, and 2) to determine if autoimmunity was associated with spermatozoal degeneration. Seventy-five percent of the affected roosters did not ejaculate large percentages of degenerate spermatozoa at 20 wk of age, approximately the age of sexual maturity. Rather, seminal quality gradually declined over the next 6 wk, as both ejaculate volume and number of spermatozoa ejaculated increased. The evaluation of testicular and excurrent duct tissues via immunofluorescence failed to reveal either IgY or IgA associated with spermatozoa. While histological examination revealed greater lymphocyte numbers (P less than .05) in the proximal ductus deferens, these cells were not associated with spermatozoa nor spermatozoal clumping. While spermatozoal degeneration tends to be latent at the onset of semen production, it does not appear to be due to spermatozoal autoimmunity. PMID- 2323999 TI - Preparation and short-term culture of enriched populations of guinea pig spermatocytes and spermatids. AB - In order to study acrosome biogenesis in vitro, the authors developed techniques for the isolation and culture of enriched populations of guinea pig spermatogenic cells using a modification of the technique of Romrell et al (1976). The modifications include changes in the medium, enzyme concentrations, cell loads for gradient separations, and sedimentation times. Three major cell populations were pooled: Pachytene spermatocytes (PS: 2.0 x 10(7), 80-85% pure), round spermatids, (RS: 1.2 x 10(8), 80-85% pure), and condensing spermatids (CS: 2.0 x 10(8), 50-60% pure, contaminated with residual bodies). The ultrastructural properties of the isolated cells appeared similar to those of cells in situ. PS were 3-4 times more active than RS and 10 times more active than CS in synthesizing proteins. These experiments demonstrate that highly enriched populations of guinea pig spermatogenic cells can be isolate, and that these cells can be cultured in the presence of radioactive precursors for studies of protein synthesis during spermatogenesis. PMID- 2324000 TI - Initial characterization of factors from testicular fluid which alter in vitro androgen secretion by normal rat Leydig cells. AB - It is known that testicular interstitial fluid (TF) contains thermolabile factors that can alter in vitro production of androgens by the Leydig cells. The net stimulatory activity of this fluid increases in association with the disruption of spermatogenesis. The identity of the active agent(s) in TF is not known. Therefore, the authors used gel-liquid chromatography to initially characterize TF from control and bilaterally cryptorchid animals. The stimulatory activity of TF was retained on Concanavalin A Sepharose columns. Gel filtration on Ultrogel AcA 44 suggested a molecular size between 40 and 90 kD. The unfractionated fluid from control and bilaterally cryptorchid rats, as well as the chromatographic fractions containing stimulatory activity, were further resolved by SDS-PAG electrophoresis. At least three bands representing glycoproteins with apparent molecular size between 57 and 75 kD were seen in all samples containing stimulatory activity. No difference in the pattern of protein bands was seen between TF from control and bilaterally cryptorchid testes. However, samples reduced with beta-mercaptoethanol showed protein bands with apparent molecular size of 78 and 118 kD which were present only in unpurified control TF. These data support the possibility that the stimulatory substance in TF from control and bilaterally cryptorchid testes is a glycoprotein with a molecular size between 57 and 75 kD. Differences in the bioactivity of the unfractionated TF may be due in part to the presence of additional larger protein molecules in the control TF. PMID- 2324001 TI - Proteins in luminal fluid of the ram excurrent ducts: changes in composition and evidence for differential endocytosis. AB - Rete testis fluid (RTF) and luminal fluid collected by micropuncture at selected epididymal sites were analyzed to characterize the spectrum of proteins and to quantify the net gain or loss of total/bulk protein and androgen-binding protein (ABP) between successive regions within the ductus epididymidis. Based on one dimensional SDS gel electrophoresis, the spectra of proteins in RTF and fluids from the proximal, central, and distal caput through proximal corpus epididymidis differed from each other. Concentrations of sperm, bulk protein, and ABP increased from the rete testis through the central caput epididymidis. Electron microscopic studies following intraluminal microinjections of RTF proteins conjugated to colloidal gold at specific sites in the excurrent ducts revealed that 145 times more protein-gold was endocytosed in the ductuli efferentes than in any of the four regions of the caput epididymidis. Thus, ductuli efferentes were the major extra-testicular site of endocytosis of bulk protein present in RTF; at least a portion of the uptake was specific. On a per sperm basis, the amount of protein present in the central caput epididymidis was less than 15% of that leaving the testis. Although most of the protein present in RTF (greater than or equal to 86 mg/d) must be absorbed in the ductuli efferentes and the initial segment of the epididymis and replaced by newly secreted proteins (greater than or equal to 34 mg/d), there was negligible loss of ABP in these regions. Net loss of ABP occurred primarily in the distal caput and proximal corpus epididymidis. These studies demonstrate that ABP is spared from endocytosis along with the bulk protein in RTF and conserved for functions in epididymal regions far distal to the site of bulk protein loss. PMID- 2324002 TI - Leydig cell cytoplasmic content is related to daily sperm production in men. AB - The relationship between the abundance of specific Leydig cell organelles and daily sperm production (DSP) was determined. Testes from 10 men (26-53 years of age) were obtained at autopsy within 10 h of traumatic death or heart failure and fixed by vascular perfusion. Testicular tissue was processed for light and electron microscopy. DSP/testis and Leydig cell cytoplasmic volume/testis were determined by stereology of histologic sections. The Leydig cell organelle content was determined by point counting electron micrographs for smooth endoplasmic reticulum (SER), rough endoplasmic reticulum, mitochondria, lipofuscin pigment, lipid, Golgi bodies, and Reinke crystals. Men were divided equally into two groups based on DSP/testis. Men with low DSP/testis had less SER volume density (P less than 0.01) and lower SER volume per testis (P less than 0.05) than men with high DSP. Other organelles were unrelated to DSP. When all men were combined, the volume density of SER (r = 0.80; P less than 0.01), the volume SER per testis (r = 0.69; P less than 0.05), and the volume SER per Leydig cell (r = 0.84; P less than 0.01) were significantly related to DSP. Hence, there appears to be a significant relationship between Leydig cell SER and the level of spermatogenesis in men. PMID- 2324003 TI - Metabolism of 5 alpha reduced androgens by various tissues of the male rat. AB - Since an animal model for the study of peripheral androgen metabolism is needed, we studied the metabolism of 5 alpha-reduced androgens in various tissues of the rat. Labeled DHT and 3 alpha androstanediol (3 alpha diol) were added to tissue minces of male rat scrotal skin, muscle, prostate, or liver. Conversion ratios of the interconverting pair DHT in equilibrium with 3 alpha diol or the formation of the respective glucuronides (G) were determined over a 3 h period. Major differences in the activity and the oxidation/reduction relationship were observed between tissues. Scrotal skin was very active and balanced in the DHT in equilibrium with 3 alpha diol interconversion (31 and 33%/100 mg/3 h, respectively, whereas liver was minimally active (3.1/2.7%). 3 alpha reduction was prominent in muscle (37.0/2.7%), although 3 alpha oxidation was more active in prostate (6.0/31.5%). Steroid glucuronidation also differed in the various tissues. Sexual skin formed about 2% 3 alpha diol G, but much smaller amounts of DHTG. Liver, muscle, and prostate formed minimal (less than 0.2%) 3 alpha diol G, although liver synthesized 1.2% of DHTG. Addition of DHT or 3 alpha diol increased formation of the respective glucuronides by liver, whereas DHT blocked the synthesis of 3 alpha diol G, and 3 alpha diol markedly increased formation of 3 alpha diol G in skin. These studies indicate a similarity in DHT metabolism between rat and human sexual skin and a high rate of glucuronidation compared with other tissues. The pathway of 3 alpha diol G formation in skin is DHT----3 alpha diol----3 alpha diol G. Steroid 3 alpha oxidase is more active than 3 alpha reductase in muscle whereas 3 alpha oxidase predominates in prostate. This may be a mechanism whereby DHT levels and action as a nuclear androgen is favored in prostate, whereas testosterone is the major androgen in muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324004 TI - Characterization of sulfhydryl proteins involved in the maintenance of flagellar straightness in hamster spermatozoa. AB - Hamster caput epididymal spermatozoa exhibit a marked 90-180 degree bend when induced to acquire progressive motility in vitro (Cornwall et al, 1988). Flagellar bending is prevented by oxidizing sperm sulfhydryl (SH) groups with diamide. In the present study, the authors examined the SH proteins involved in sperm flagellar bending using two-dimensional polyacrylamide gel electrophoresis and monobromobimane, an SH-specific fluorescent dye. Proteins extracted from samples containing bent caput spermatozoa contained more reduced SH than the same proteins extracted from straight caput spermatozoa. To further characterize these sperm SH proteins, caudal epididymal spermatozoa that exhibited straight flagella were induced to undergo flagellar bending by treatment with the SH reductant dithiothreitol. Specific proteins of 85-94 kDa, 50-55 kDa and 35-40 kDa, which were rich in SH groups when extracted from samples containing bent caput spermatozoa, were also SH-rich in samples containing bent cauda spermatozoa. These studies suggest that oxidation of specific SH proteins may be important for maintaining sperm flagellar morphology. PMID- 2324005 TI - Characterization of a new superfusion, two-compartment culture system for Sertoli cells: influence of extracellular matrix on the cell permeability and dynamics of transferrin secretion. AB - A new superfusion two-compartment culture system was developed in the laboratory of the author and was used to investigate the influence of testicular extracellular matrix on barrier formation by Sertoli cells in culture, and the acute dynamic changes in the bidirectional secretion of transferrin. Only Sertoli cells growing on extracellular matrix formed a monolayer that was specifically impermeable to inulin, peroxidase, and FSH, but did not affect the passage of testosterone. Moreover, in these conditions, they were highly polarized morphologically. The bidirectional secretion (basal/apical ratio) of transferrin was affected by the duration of the stationary culture preceding the superfusion. After 2 days of culture, the amount of transferrin secreted during the subsequent 20 h superfusion was higher in the basal chamber than in the apical chamber. In contrast, after 5 days of culture, the amount of secreted transferrin was higher in the apical compartment. The author compared his data with those previously reported by other authors, using stationary two-compartment chambers. PMID- 2324006 TI - Sialyglycoconjugates release during in vitro capacitation of human spermatozoa. AB - Modifications of the human sperm surface during incubation in capacitating conditions were studied by radiolabeling terminal sialic acid residues of cell surface glycoconjugates using the sodium metaperiodate/sodium tritiated borohydride method. During in vitro capacitation, sialyglycoconjugates were released from the human sperm surface according to well reproducible kinetics. This release could be inhibited by the presence of seminal plasma in the capacitation buffer. Two principal size classes of sialyglycoconjugates were detected in the capacitation medium and analyzed by gel filtration chromatography and SDS-PAGE. The smaller class was characterized by glycopeptides less than 5,000 Da, whereas the larger class was characterized by two sialyglycoproteins of approximately 15,000-16,000 and 22,000-23,000 Mr. The role of human albumin, a key component of the capacitation buffer, in the removal of these molecules from the sperm surface was studied in light of its constant association with large amounts of released material. PMID- 2324007 TI - Altromycins, novel pluramycin-like antibiotics. I. Taxonomy of the producing organism, fermentation and antibacterial activity. AB - The altromycins are novel anthraquinone-derived antibiotics related to the pluramycins. They are produced by an actinomycete, AB 1246E-26, which was isolated from a South African bushveld soil. The altromycins have Gram-positive antibacterial activity with MICs of 0.2 to 3.12 micrograms/ml against Streptococci and Staphylococci. PMID- 2324008 TI - Altromycins, novel pluramycin-like antibiotics. II. Isolation and elucidation of structure. AB - A novel complex of Gram-positive antibiotics was produced from the fermentation of an actinomycete culture AB 1246E-26. The antibiotics were recovered from the whole fermentation broth by extraction with organic solvent and isolated using counter-current chromatography. UV and IR data place these compounds in the anthraquinone-derived class of antibiotics. Mass spectral and NMR data indicate a new complex of compounds related to, but distinctly different from the pluramycin type antibiotics. PMID- 2324009 TI - Novel antibiotics, furaquinocins A and B. Taxonomy, fermentation, isolation and physico-chemical and biological characteristics. AB - Two novel antibiotics, furaquinocins A and B were isolated from the culture broth of Streptomyces sp. KO-3988. These antibiotics possess cytocidal activities against HeLa S3 cells in vitro at concentrations of 3.1 micrograms/ml for A and 1.6 micrograms/ml for B. Neither substance possessed antimicrobial activities against Gram-positive and Gram-negative bacteria, fungi or yeast at a concentration of 1,000 micrograms/ml. PMID- 2324010 TI - LL-D49194 antibiotics, a novel family of antitumor agents: taxonomy, fermentation and biological properties. AB - A novel family of antitumor antibiotics, designated LL-D49194, was isolated from the fermentation broth of an actinomycete strain identified as Streptomyces vinaceus-drappus. LL-D49194 alpha 1 and beta 2 were active against Gram-positive and inactive against Gram-negative bacteria in vitro. The beta 1 component was not active against either Gram-positive or Gram-negative bacteria. These antibiotics exhibited significant in vivo activities against several murine tumors, albeit with differing potencies. PMID- 2324011 TI - SF2487, a new polyether antibiotic produced by Actinomadura. AB - A new antibiotic SF2487 has been isolated from the culture broth of Actinomadura sp. SF2487. The structure of antibiotic SF2487 was determined by spectroscopic analyses of the sodium salt and X-ray diffraction analysis of the silver salt. The antibiotic represents a new member of polyether group antibiotics known as the acyltetronic acid type 4. The antibiotic is weakly active against Gram positive bacteria and exhibits antiviral activity against influenza virus in vitro. PMID- 2324012 TI - Studies on new dehydropeptidase inhibitors. III. Biological properties of WS1358A1. AB - WS1358A1, a novel inhibitor of renal dehydropeptidase (DHP), augmented the urinary recovery of a carbapenem antibiotic imipenem and improved its protective effect in experimental infections when simultaneously administered to mice with the antibiotic. WS1358A1 was a competitive DHP inhibitor with a Ki value of 1.6 x 10(-7) M. PMID- 2324014 TI - Study to the biosynthesis of the rifamycin-chromophore in Nocardia mediterranei. PMID- 2324013 TI - Chemical modification of erythromycins. II. Synthesis and antibacterial activity of O-alkyl derivatives of erythromycin A. AB - A series of O-alkyl erythromycin A derivatives have been synthesized and their antibacterial activities compared with those of erythromycin A (1) and 6-O methylerythromycin A (3). Methylation of the hydroxyl groups of erythromycin A analogue proceeded stepwise by the two main pathways beginning at the C-6 and C 11 positions, individually. O-Alkylation, other than methylation, took place at the C-11 hydroxyl group exclusively. Among O-alkyl derivatives, 6,12-di-O methylerythromycin A (5) showed comparable in vitro antibacterial activity to those of 1 and 3. 11-O-Methylerythromycin A (8) was slightly less active than 1. O-Methylation at the C-4" position resulted in a decrease of antibacterial activity. PMID- 2324015 TI - Absorption, tissue distribution and excretion of 19-deformyldesmycosin derivatives, new 16-membered macrolides, in mice. PMID- 2324016 TI - Visualization and functional testing of acetylcholine receptor-like molecules in cochlear outer hair cells. AB - The efferent nerve endings at outer hair cells (OHCs) have been suggested to regulate active mechanical processes in the cochlea. The discovery of acetylcholine (ACh)-producing and -degrading enzymes in these synapses gave rise to the speculation that ACh might be one of the efferent transmitters. However, there has as yet been no identification and characterization of any corresponding receptor in OHCs which is required for further clarification of this question. In the present paper existence, location and first characterization of acetylcholine receptors (AChRs) in OHCs are reported. Using two anti-AChR monoclonal antibodies, AChR epitopes were found forming a cup at the basal end of the OHCs opposite to the efferent nerve endings. Furthermore, the studied molecules could be shown to extend through the cell membrane. In addition, the denervated OHC AChR-epitopes seem to move by lateral diffusion. Application of Carbachol and ACh to the basal pole of OHCs induced a weak, reversible cell contraction. Pharmacological controls revealed, that hte motile responses were mediated by the AChRs. PMID- 2324017 TI - A combined sensitivity for frequency and interaural intensity difference in neurons in the auditory midbrain of the grassfrog. AB - The relation between spectral tuning and sensitivity for interaural intensity difference (IID) was studied for single units in the auditory midbrain of the grassfrog. The stimuli consisted of sequences of pure tones of different frequency and interaural intensity differences presented by means of a closed sound system. At best excitatory frequency, three types of binaural interaction were observed: E0 (one ear excitatory 23%), EE (both ears excitatory 9%) and EI (one ear excitatory, the other inhibitory 67%). For a considerable number of units different types of binaural interaction were observed for different stimulus frequencies. More than 30% of the binaural units had multiple excitatory and inhibitory regions in their spectrotemporal selectivity. E0 and EI units had uniformly distributed best frequencies, EE units generally had best frequencies near 1.0 kHz. The E0 and EE categories had response latencies less than about 70 ms whereas EI units could have longer latencies. Most EE and all EI category units had sigmoidally shaped IID-rate curves. About 40% of the units had a combined sensitivity for sound spectrum and IID which was invariant to overall stimulus intensity. For nearly all EI units the inhibitory influence of the ipsilateral ear was confined to frequencies in the 0.4-1.6 kHz range and was not correlated with a unit's best frequency. By means of a simple additive model we demonstrated that determination of sound source laterality can be achieved by ensemble coding in the auditory midbrain. PMID- 2324018 TI - Neural sensitivity to phase of high frequency tones. AB - The response of fibres of the auditory nerve and neurons of the inferior colliculus of the cat to harmonic two-tone complexes was studied. The components (primaries) had frequencies which were integral multiples of the characteristic frequency of the cell under study. This gave rise to distortion products at the characteristic frequency of the cell. The response of these cells to distortion products at their characteristic frequency was found to be dependent upon the relative phase of the primaries. This was observed for primaries of high frequency as well as those of low frequency. The response to distortion in the cochlear microphonic was also dependent upon the relative phase between harmonic primaries. PMID- 2324019 TI - Mutant golden hamsters with an abnormal outer hair cell stereociliary arrangement. AB - A new malformation of the inner ear was found in golden hamster reared at our institute. It was studied using electron microscope and auditory electrophysiological measurements including auditory brainstem response (ABR), whole nerve action potential (AP) cochlear microphonic (CM) potential, and the summating potential (SP). The stereocilia on individual first row of outer hair cells in the hamsters with malformed inner ears (F-K hamsters) were arranged in a triple W form, but the entire bundle of stereocilia was irregular in orientation. These anomalies were seen in approximately 70 to 85% of sensory hairs, in all rotations, with no difference between the right and left sides. The cuticles of the first row of outer hair cells were displaced, but lower portions did not appear to be affected. ABR and SP revealed no differences from normal hamsters and it is believed that the F-K hamsters' hearing ability was normal. The CM potential and the amplitude of AP in the F-K hamsters were significantly lower, at 50 to 80 dB sound pressure level (SPL). The linear portions of the CM input output relation curve were separated by 4 to 6 dBSPL and the saturating voltage levels differed by 2.5 to 3.0 microV. Based on these results, the actually measured CM potentials were shown to represent a summation of the reaction of the three individual rows of outer hair cells. PMID- 2324020 TI - Synaptic potentials in afferent fibers innervating hair cells of the lateral line organ in Xenopus laevis. AB - Spontaneous synaptic activity in afferent fibers innervating hair cells of the lateral line organ was monitored with micropipettes at visually identified locations near the peripheral terminations of the fibers. Spontaneous action potentials as well as spontaneous excitatory post-synaptic potentials (EPSPs) were observed. Some action potentials were preceded by EPSPs. Most EPSPs did not reach threshold to generate action potentials. The frequency of occurrence of spontaneous EPSPs was related to the number of neuromasts innervated by a fiber. Single EPSPs were most readily observed in fibres innervating only a few neuromasts. Perfusion of the synapse with solutions containing cobalt reversibly diminished discharge rate by reducing the occurrence of EPSPs. Manganese produced similar effects on discharge rate. The blockage of spontaneous EPSPs by cobalt, an agent that can block voltage-dependent transmitter release, supports the hypothesis that spontaneous discharge in afferent fibers of the lateral line organ is due to voltage-dependent release of transmitter from the hair cells. PMID- 2324021 TI - Can shape deformations of the organ of Corti influence the travelling wave in the cochlea? AB - Via their motile reactions outer hair cells may produce oscillatory power or amplify the fluid waves in the cochlea. When the cells move or change their lengths, the organ of Corti (OC) will change its shape. This paper describes the consequences of such shape changes for the physics of cochlear waves. The assertions posed are based on a mathematical derivation but the major conclusions can be grasped without following the mathematics in detail. There are two basic types of OC deformations. In the first type the net cross-sectional area of the OC is periodically varying, in the second type--the central subject of this paper -is is not. It is shown that for the latter type of OC shape deformation there is no interaction with the cochlear fluids, at least for long waves. Hence, in this case the outer hair cells cannot amplify cochlear waves. The other type of OC deformation has a better coupling with the cochlear waves. However, much of the pressure developed by oscillating hair cells is spent in the 'wrong' way, namely, by squeezing fluid lengthwise through the narrow channel of the OC. Therefore, in this mode power transfer from cochlear hair cells to cochlear fluids (and from there to the basilar membrane) would be very inefficient. PMID- 2324022 TI - A psychophysical study of spectral hyperacuity. AB - Frequency modulation (FM) of primary tones is transposed to FM of distortion products which are lower in frequency. Since the auditory system is more sharply tuned at low frequencies there is an increase in sensitivity to FM via this transposition. The increased sensitivity is reduced when distortion products are masked. PMID- 2324023 TI - Horror story. PMID- 2324024 TI - Time for a change: women's health education in Canadian university schools of nursing. AB - As a group, women are the major users of the health care system, both directly, in terms of their own health, and indirectly, as the custodians of their family's health. In the past 10 years, there has been a growing awareness of the particular health concerns of women. One of the results of this increased awareness has been the development of courses that address these concerns. Most have been offered through Women's Studies programs. Recently, a growing awareness of these issues has developed among nurses and nurse educators. However, as Saunders and Taylor (1985) point out, "Nurse educators have been slow to develop courses that address women's health issues" (p. 25). My purpose in conducting this study was to survey university schools of nursing in Canada to discover if topics relating to women's health are incorporated into the nursing education curricula. I found that nursing education curricula tend to present women's health issues in a traditional, medically defined manner, focusing on childbearing and reproductive issues. The important problems of women and poverty, the social construction of diseases, and the social context of women's health were addressed much less frequently. PMID- 2324025 TI - Professional and executive women: health and lifestyle characteristics. AB - Selected health characteristics of professional and executive women, and relationships among physical fitness, physical activity, and health characteristics in this group were examined. The health characteristics examined included stress, Type A patterns of behavior, substance use (alcohol, tranquilizers, and smoking), nutrition, health practices, safety, and relaxation. A convenience sample of 104 executive/professional women between the ages of 30 and 59 years, who were working full time, were administered the Canadian Standardized Test of Fitness (Step-Test) to measure cardiovascular fitness, the Framingham Type A Questionnaire, the Personal Life-style Questionnaire, the Physical Activity Questionnaire, and a visual analog scale to measure stress. The results suggest that executive women are significantly more fit than Canadian norms and that they tend to consume more alcohol and to smoke less. Demographically, they are more likely to be unmarried, childless, and have higher incomes than other Canadian women. Fitness levels are only associated (inversely) with smoking habits. Of interest are the high Type A scores, which are almost twice that of the Framingham norms. The possible consequences and implications of these findings are discussed. PMID- 2324026 TI - Relationships among hardiness, social support, severity of illness, and psychological well-being in women with rheumatoid arthritis. AB - The purpose of this study was to examine the relationships among hardiness, social support, severity of illness, and psychological well-being in women with rheumatoid arthritis who were being seen on an outpatient basis. Questionnaires were administered, to 122 women, assessing hardiness, social support, and psychological well-being. Severity of illness was determined by assessment of joint function, sedimentation rates, and length of morning stiffness. Significant correlations were found between (a) hardiness and the number of persons in the social support system, (b) hardiness and satisfaction with social support, (c) hardiness and psychological well-being, (d) the number of persons in the social support system and satisfaction with social support, (e) the number of persons in the social support system and joint function, (f) satisfaction with social support and psychological well-being, and (g) length of morning stiffness and psychological well-being. Stepwise regression analysis indicated that satisfaction with social support, hardiness, and length of morning stiffness (in that order) were the best predictors of psychological well-being. The findings suggest that these three factors play a significant role in the identification of women with rheumatoid arthritis who are more able to cope with the stressful ramifications of their disease. PMID- 2324027 TI - Women's choice of childbirth setting. AB - As part of a larger study on women's views of the childbirth experience, this study was focused on women's choice of childbirth setting. Sixty-one Lamaze prepared, married multigravidae between the ages of 21 and 37 and experiencing a normal pregnancy were interviewed twice: at 36-38 weeks gestation in their homes and during their postpartum stay in the hospital. Data were collected using (a) two semistructured interview guides consisting of open-ended questions about choosing a caregiver and the place of birth and about describing the actual childbirth experience, (b) a self-administered sociodemographic questionnaire, and (c) an obstetrical and infant data form. The tape-recorded interviews were transcribed verbatim. Qualitative data analysis was focused on reasons for choosing a hospital and a physician, reasons for choosing or not choosing a birthing room, and the outcomes of the decisions. An understanding of women's childbirth needs as reflected in their choices can suggest areas where flexibility might be built into maternity care programs. PMID- 2324028 TI - Identification of predictor variables of a postpartum emotional reaction. AB - Clinical observations and research suggest that postpartum emotional reactions (PEREA) are a widespread phenomenon. Prenatal identification of women who are at risk is essential if health professionals are to intervene and prevent long-term problems for the mother and her family. Health status, previous psychiatric history, locus of control, psychosocial assets, and life change events, as well as maternal adaptation to pregnancy and motherhood were examined in this study as possible predictor variables of a postpartum emotional reaction. Twenty-seven expectant women were assessed once prenatally and twice in the postpartum period. The data revealed that 59% of the participants, both primiparas and multiparas, experienced an increase in negative affect at some stage of the pregnancy and/or within 4 to 6 weeks postpartum. There were no significant differences between those who developed a PEREA and those who did not on the following variables: planned versus unplanned pregnancy, desired versus undesired pregnancy, attendance at prenatal class, and feeding plans. There was a significant association (p less than .01) between breastfeeding and the occurrence of a PEREA at 4 to 6 weeks postpartum among the primiparas. The study demonstrated that there was no single cause but several factors that, if present in combination, were predictive of an emotional reaction postpartum. Locus of control and existing emotional reactions, especially prenatal depression, were the most important predictor variables. The individual's ability to adapt to day-to-day life was influenced by the presence or absence of a combination of factors. These included preexisting emotional reactions, perceived locus of control, health status, and/or stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324029 TI - Mothers with chronic illness: a predicament of social construction. AB - In the context of a larger qualitative study, a database including extensive interviews with a subset of sixteen chronically ill mothers was obtained. Secondary analysis revealed that the women's concerns about themselves and their children included issues of performance, availability, dependency, and socialization. Further, these women reported that the health care system seemed incapable of recognizing or accounting for the profound interrelationship between their mothering and their illness. Analysis of these findings in terms of the conflicting social obligations inherent in the roles of "mother" and of "chronically ill person" provides a means by which to understand the women's impressions that it was a contradiction in terms to be both an effective mother and a good patient. PMID- 2324030 TI - "Euch, those are for your husband!" examination of cultural values and assumptions associated with breast-feeding. AB - Examination of the assumptions underlying research and educational resources on breast-feeding reveals bias and a lack of data to substantiate perceived facts. In this paper four methods of examining research to assist in identifying assumptions and bias in breast-feeding research are presented. Four methods are (a) examining past research, (b) examining cross-cultural research, (c) asking anthropological questions, and (d) using inductive research techniques to reexamine the problem. Such techniques reveal new insights and permit the identification of new directions for breast-feeding research. PMID- 2324031 TI - Chronic leukemias. PMID- 2324032 TI - Determination of sulfite in foods and beverages by ion exclusion chromatography with electrochemical detection: collaborative study. AB - A liquid chromatographic (LC) method for determination of total sulfite in foods and beverages by alkali extraction followed by ion exclusion chromatographic separation and electrochemical detection (IEC-EC) was collaboratively studied by 9 laboratories. Blind duplicate samples of starch, diluted lemon juice, wine cooler, dehydrated seafood, and instant mashed potatoes were analyzed without spiking and with added sulfite at 2 levels. The initial sulfite levels varied from 0 to 384 ppm SO2, and the levels added varied from 10 to 400 ppm. The initial sulfite levels determined by the IEC-EC method and the Monier-Williams method were in good agreement. Recovery of added sulfite by the IEC-EC method was generally higher than that by the Monier-Williams method. Within-laboratory repeatability (RSDr) for the IEC-EC method varied from 4.4 to 26.0%, and overall reproducibility (RSDR) varied from 8.5 to 39.3%. The collaborators found the method to be fast, sensitive, and easy to use, which makes it a useful alternative to the Monier-Williams method. The method has been adopted official first action. PMID- 2324033 TI - Determination of free (pH 2.2) sulfite in wines by flow injection analysis: collaborative study. AB - A method for the determination of free sulfite in wine by flow injection analysis (FIA) is described. The method involves liberation of sulfur dioxide from the wine at pH 2.2, with detection by decolorization of a malachite green solution. The method was collaboratively studied, and the results indicated an average reproducibility of 12% for white wine samples (average level 12.1 ppm SO2) and 26% for red wine samples (average level 3.1 ppm). When the FIA method was compared to an aeration/oxidation method, the results indicated a high degree of correlation between the 2 methods. The FIA method has been adopted by AOAC official first action. PMID- 2324034 TI - Determination of ten N-nitrosoamino acids in cured meat products. AB - A rapid, sensitive, and accurate solid-phase extraction method was developed for the measurement of 10 N-nitrosoamino acids (NAAs) in cured meat products. In the procedure, the comminuted meat was mixed with sulfamic acid and Celite, and then added to a glass column containing anhydrous sodium sulfate. The column was washed with pentane, and the NAAs were eluted with ethyl acetate. The eluate was concentrated, then derivatized with diazomethane followed by acetic anhydride pyridine reagent. The NAA methyl esters and their acylated hydroxy derivatives were separated by gas chromatography on a DB-5 fused silica capillary column and quantitated with a thermal energy analyzer, a chemiluminescence detector specific for nitric oxide derived from the thermal denitrosation of nitrosamines. Recovery of 10 of the NAAs exceeded 75% at the 10 ppb level. The method is applicable to a wide range of cured meat products. PMID- 2324035 TI - Colorimetric deoxyribonucleic acid hybridization assay for rapid screening of Salmonella in foods: collaborative study. AB - A collaborative study was performed in 11 laboratories to validate a colorimetric DNA hybridization (DNAH) method for rapid detection of Salmonella in foods. The method was compared to the standard culture method for detection of Salmonella in nonfat dry milk, milk chocolate, soy isolate, dried whole egg, ground black pepper, and raw ground turkey. Samples inoculated with high (0.4-2 cells/g) and low (0.04-0.2 cells/g) levels of Salmonella and uninoculated control samples were included in each food group analyzed. There was no significant difference in the proportion of samples positive by DNAH and culture procedure for any of the 6 foods. The colorimetric DNA hybridization assay screening method has been adopted official first action as a rapid screening method for detection of Salmonella in all foods. PMID- 2324037 TI - Rapid screening method for deoxynivalenol in agricultural commodities by fluorescent minicolumn. AB - A rapid screening procedure based on the selective adsorption of deoxynivalenol (DON) from extracts of wheat and corn has been developed. DON is extracted from the sample with acetonitrile-water (85 + 15) and partially purified on a preparative minicolumn. Solvent is evaporated and the residue is dissolved in toluene-acetone (95 + 5) and chromatographed on a novel detector minicolumn which selectively adsorbs DON. A blue fluorescence is produced when the column is heated 5 min at 100 degrees C. The procedure is capable of detecting DON at greater than or equal to 500 ng/g. Forty-three wheat samples, contaminated with DON at 60-6300 ng/g, were assayed by gas chromatography-mass spectroscopy (GC-MS) of the heptafluorobutyryl derivative of DON and by the selective adsorption procedure. Comparison of results showed 91% agreement between data from the 2 methods. Selective adsorption assays were positive for all samples that were greater than or equal to 500 ng/g by GC-MS (no false negatives) and were negative for 85% of samples less than 500 ng/g (4/27 false positives). These four samples contained greater than 200 ng/g by GC-MS. Samples of wheat (64), corn (23), soybeans (8), and sorghum (6) were extracted and extracts were assayed by thin layer chromatography and the selective adsorption procedure. Selective adsorption assays agreed with TLC results. PMID- 2324036 TI - Improved spectrophotometric determination of cyclopiazonic acid in poultry feed and corn. AB - An improved visible spectrophotometric method has been developed for cyclopiazonic acid in poultry feed and corn. The method is based on the reaction of cyclopiazonic acid with Ehrlich reagent and detection at 580 nm. Reaction conditions were optimized with respect to reaction and measurement times and acid and Ehrlich reagent concentrations. Calibration curves were linear from 1 to 20 micrograms cyclopiazonic acid in 3 mL Ehrlich reagent, with a lower detection limit of 0.08 mg/kg for 50 g samples of poultry feed and corn. Recoveries from 50 g samples of poultry feed spiked with cyclopiazonic ranging from 0.16 to 1.20 mg/kg averaged 93.8%. Moldy corn and poultry feed samples analyzed by this method contained between 1 and 4 mg/kg cyclopiazonic acid. PMID- 2324038 TI - Criteria for determining purity of Fusarium mycotoxins. AB - Physical and chemical properties that may be used to determine the purity of several Fusarium mycotoxins have been investigated. A combination of analytical procedures, which include high performance thin-layer chromatography (HPTLC), liquid chromatography (LC), gas chromatography (GC), gas chromatography/mass spectrometry (GC/MS), ultraviolet spectrometry (UV), and nuclear magnetic resonance (NMR) spectrometry have been used to examine mycotoxin standards obtained from commercial sources and from laboratory fermentations. Results of this investigation indicate that commercially available standards are greater than 90% pure, but the label weight of purchased reference standards in individual containers should be verified. Mycotoxin standards, determined to be greater than 98% pure by HPTLC, LC, and GC/MS, were examined by UV spectrometry and the coefficients of extinction were determined. An interlaboratory study, involving 5 collaborators who determined coefficients of extinction (in methanol) for identical samples, gave the following results: alpha-zearalenol (lambda 236 = 28 538 +/- 558); beta-zearalenol (lambda 238 = 24 963 +/- 747); deoxynivalenol (lambda 219 = 6395 +/- 349, lot 1), (6020 +/- 228, lot 2); and T-2 toxin (lambda 202 = 3681 +/- 255). UV maxima and coefficients of extinction are also reported for HT-2 toxin (lambda 202 = 1959), diacetoxyscirpenol (lambda 203 = 2487), neosolaniol (lambda 203 = 2644), nivalenol (lambda 220 = 5142), and fusarenon-X (lambda 217 = 5997). PMID- 2324039 TI - Gas chromatographic-electron capture detection method for determination of 29 organochlorine pesticides in finished drinking water: collaborative study. AB - A joint U.S. Environmental Protection Agency/AOAC interlaboratory method validation study was conducted on EPA Method 508, Determination of Chlorinated Pesticides in Water by Gas Chromatography with an Electron Capture Detector, to determine the mean recovery and precision for analyses of 29 pesticides in reagent water and finished drinking water. The study design was based on Youden's nonreplicate plan for collaborative tests of analytical methods. The waters were spiked with 29 pesticides at 6 concentration levels, as 3 Youden pairs. Eleven volunteer laboratories extracted the spiked test waters with methylene chloride, performed a solvent exchange with methyl tert-butyl ether, and analyzed an aliquot of each extract by gas chromatography with electron capture detection. Results were analyzed using an EPA computer program, interlaboratory Method Validation Study (IMVS), which measured recovery and precision for each of the 29 pesticides and compared the performance of the method between water types. Method 508 was judged acceptable for all analytes tested. Only 3 analytes (alpha chlordane, 4,4'-DDE, and methoxychlor) exhibited practical significant matrix effects. The method has been adopted official first action. PMID- 2324040 TI - Hypoglycin A content in the aril, seeds, and husks of ackee fruit at various stages of ripeness. AB - Recently, hypoglycin A (HG-A), a natural toxin, was detected in canned ackee fruit. To determine the source of contamination, the HG-A content in the ackee fruit components (aril, seeds, and husks) at various stages of ripeness was determined by a method using an amino acid analyzer. HG-A concentrations in the unripe ackee fruit components were 939, 711, and 41.6 mg/100 g of seed, aril, and husk components, respectively. Analysis of the ripe fruit components showed that HG-A in the seed decreased to 269 mg/100 g and remained unchanged in the husk while the concentrations in the edible ripe aril decreased below the detection limit of 1.2 mg/100 g. PMID- 2324041 TI - Determination of copper, iron, and nickel in oils and fats by direct graphite furnace atomic absorption spectrometry: summary of collaborative study. AB - A collaborative study of a method for the determination of copper, iron, and nickel in edible oils and fats by direct graphite furnace atomic absorption spectrometry was recently conducted by the International Union of Pure and Applied Chemistry. The quantitation limits of the method are 5 micrograms/kg for copper and 10 micrograms/kg for iron and nickel. The method has been adopted official first action as an IUPAC-AOAC method. PMID- 2324042 TI - Mass spectrometric confirmation of the presence of N-nitrosopyrrolidine in instant coffee. AB - Traces of N-nitrosopyrrolidine (NPYR) may occur in some samples of both instant coffee and fine-ground roasted coffee. The identity of NPYR in 2 samples of instant coffee was confirmed by mass spectrometry as well as by liquid chromatography-thermal energy analysis. A 2-step cleanup procedure, involving fractionation on basic alumina followed by gradient elution on reverse-phase C18 cartridge, is described that allows full-scan mass spectrometric confirmation of NPYR in tested samples. PMID- 2324043 TI - Quantitative multiresidue analyses for volatile organics in water and milk, using a fused silica open-tubular wide-bore capillary column and automated headspace gas chromatography. AB - A modified multiresidue capillary gas chromatographic (GC) procedure has been developed using automated headspace sampling and a wide-bore fused silica open tubular (FSOT) capillary column for the determination of volatiles in water and milk. Compounds are quantitated by the method of standard additions. An IBM System 9000 computer with the CAPMC3 chromatographic applications package and a BASIC linear regression program are used for data reduction. Data are presented for solutions prepared by fortifying water and milk with volatile solvents such as acetone, methyl ethyl ketone, benzene, methylene chloride, and chloroform, which are commonly used in the manufacture of packaging materials and adhesives. The wide-bore FSOT capillary columns showed dramatically improved detection for certain compounds, compared with normal-bore capillary GC columns. Data presented for various chemicals demonstrate the improved limits of detection from the use of automated headspace gas chromatography with wide-bore capillary columns and flame ionization detection. PMID- 2324044 TI - "Emergency". PMID- 2324045 TI - The advanced biomedical photography class at RIT. PMID- 2324046 TI - More on Kirlian photography. PMID- 2324047 TI - Attention authors. PMID- 2324048 TI - Playing Moses: an alternative approach to managing creative people. PMID- 2324049 TI - Exposure determination: the photographer's involvement. PMID- 2324050 TI - Sustained attention in children with autism. AB - Although many children with early infantile autism cannot maintain attention to externally imposed tasks, they may continue a repetitive behavior of their own choosing for long periods of time. This study examined the performance of autistic and mental age matched normal children on a Continuous Performance Test of sustained attention. Results suggest that autistic children's difficulties in sustaining attention on imposed tasks may be attributable partly to a developmental delay and partly to the motivational contingencies of task rather than to a primary impairment in the ability to sustain attention. PMID- 2324051 TI - A longitudinal study of joint attention and language development in autistic children. AB - This study was designed to examine the degree to which individual differences in gestural joint attention skills predicted language development among autistic children. A group of 15 autistic children (mean CA = 45 months) were matched with one group of mentally retarded (MR) children on mental age and another group of MR children on language age. These groups were administered the Early Social Communication Scales. The latter provided measures of gestural requesting, joint attention, and social behaviors. The results indicated that, even when controlling for language level, mental age, or IQ, autistic children displayed deficits in gestural joint attention skills on two testing sessions that were 13 months apart. Furthermore, the measure of gestural nonverbal joint attention was a significant predictor of language development in the autistic sample. Other variables, including initial language level and IQ were not significant predictors of language development in this sample. PMID- 2324052 TI - Stress, social support, and respite care use in families with autistic children. PMID- 2324053 TI - Changes in language development among autistic and peer children in segregated and integrated preschool settings. AB - Five young children with autism enrolled in a segregated class, five other children with autism in an integrated class, and four normally developing peer children in the integrated class were compared for developmental changes in language ability as measured by the Preschool Language Scale before and after training. The results, based on Mann-Whitney U tests, showed that (a) all of the children as a group made better than normative progress in rate of language development, (b) the scores of the autistic children were significantly lower than the peers before and after treatment, and (c) there were no significant differences in changes in language ability between the autistic children in the segregated and integrated classes. PMID- 2324054 TI - Perceptions of popularity among a group of high-functioning adults with autism. AB - The purpose of this study was to determine how a group of adults with autism perceived one another's interpersonal attributes and popularity. Five female and 11 male high-functioning autistic adults, 18-45 years old, participated in a social skills group together for several years. A sociogram and a questionnaire designed to determine perceptions of best looking, most athletic, and most humorous group members were administered to group members and nonhandicapped group leaders. Independent assessments of intelligence and empathy also were taken. Results indicated that perceived attractiveness and sense of humor were correlated with popularity, but group members' assessments of these attributes differed from those of the nonhandicapped group leaders. Differences between group members and group leaders responses and the implications of the results of the study for social skills training with high-functioning autistic adolescents and adults are discussed. PMID- 2324055 TI - Setting generality of peer modeling in children with autism. AB - Behavior development in normal children is greatly facilitated by peer modeling. Unfortunately, autistic children do not typically imitate their normal peers. The present study was undertaken to identify variables that facilitate the acquisition of peer imitation and promote setting generality of imitative skills once they have been acquired. We selected a common preschool activity (Follow-the Leader) as the vehicle for studying modeling effects. Four preschool children with autism took part in an intervention in which a normal peer demonstrated and, if necessary, physically prompted a variety of actions and object manipulations that defined the activity. Following training, all four children generalized their imitative skill to a new setting involving new actions and object manipulations. Results are discussed with respect to the potentially important role that the use of multiple training objects and/or responses play in enhancing attention to the model and facilitating setting generality as well as the role that intrinsically reinforcing activities may play in maintaining acquired peer imitation. PMID- 2324056 TI - Comprehension of concrete and abstract words in autistic children. AB - This study employed the Stroop paradigm to examine comprehension of single words in autistic children. The words of interest varied along a concrete-abstract dimension. In the Stroop paradigm, subjects are asked to name the color of ink in which color words are printed. Comprehension is indexed by the degree to which the automatic processing of words interferes with the color-naming task. For both concrete and abstract words, autistic children showed the same degree of interference as reading-matched controls. The findings corroborate and extend previous work suggesting that autistic children understand, and by implication, can mentally represent, at least some word meanings. PMID- 2324057 TI - Communication and sensorimotor functioning in children with autism. AB - This study examined the relationship between sensorimotor functioning and communicative intent in children with autism. Ten children with autism, four verbal and six nonverbal, served as subjects. Sensorimotor functioning was assessed on object permanence, means-end, causality, vocal and gestural imitation, the construction of objects in space and schemes for relating objects. A 2-hr communication sample was also obtained and analyzed for the number and diversity of pragmatic functions expressed. Object permanence was not significantly related to either the diversity or total number of pragmatic functions. Means-end was significantly related to both of these measures, while vocal imitation was significantly related to the total number of pragmatic functions expressed. In addition, means-end was significantly correlated with performance on the vocal and gestural imitation scales. PMID- 2324058 TI - A family history study of neuropsychiatric disorders in the adult siblings of autistic individuals. AB - The family history method was used to obtain developmental, social, and psychiatric histories on the 67 adult siblings of 37 autistic probands. Two of 67 siblings (3.0%) were autistic, three siblings (4.4%) had severe social dysfunction and isolation, 10 (15%) had cognitive disorders, and 10 (15%) had received treatment for affective disorder. This study is the first to investigate the frequency of disorders in the adult siblings of autistic probands. These results suggest aggregation of a variety of neuropsychiatric disorders in the siblings of autistic individuals. PMID- 2324059 TI - Early onset psychiatric disorder in high risk children and increased familial morbidity. AB - The relationship between child psychopathology and familial morbidity in second degree relatives was examined for children considered at risk on the basis of parental affective illness. Second degree relatives in high-risk families with no child psychopathology were no different from low-risk families in their rates of depression and anxiety. Second degree relatives in high-risk families positive for child psychopathology had significantly higher rates of depression and anxiety than relatives of low-risk children and relatives of high-risk children with no disorder. The implications of these findings are discussed with respect to risk status, prepubertal onset of psychopathology, and familial morbidity for specific psychiatric disorders. PMID- 2324060 TI - Genetic latent structure analysis of dysmorphology in attention deficit disorder. AB - Dysmorphology--in the form of minor physical anomalies--has been frequently reported in children with attention deficit disorder (ADD). The authors report an overrepresentation of minor physical anomalies in both ADD probands and their first-degree relatives. Further, ADD probands who are not dysmorphic have non-ADD relatives who are dysmorphic; this familial pattern suggests that a single underlying factor may influence transmission of both traits. A genetic latent structure model was fit to these data to describe the factor's mode of transmission. In this analysis, an autosomal dominant model emerged. Successfully fitting this model is not equivalent to testing the validity of the model itself. Meaningful tests of the model will require larger samples than available at present, and would benefit from diagnostic refinement of the ADD and dysmorphic phenotypes. PMID- 2324061 TI - Segregation and linkage analyses of Tourette's syndrome and related disorders. AB - Segregation and linkage analyses were performed with data from a large Tourette's syndrome (TS) multigenerational kindred. Results of segregation analyses were remarkably similar to some reported earlier and suggest that the mode of transmission is consistent with autosomal dominant inheritance. The analyses were done using three diagnostic schemes to specify affected family members (TS only; TS or chronic tics [CT]; and TS, CT or obsessive compulsive disorder [OCD]). The estimates of penetrance for the genotypes AA, Aa and aa (A denotes the susceptibility allele) in the analyses including relatives with TS, CT or OCD were 0.99, 0.99 and 0.00, respectively, for males and 0.70, 0.70 and 0.00 for females. Pairwise linkage analyses with 140 marker loci failed to identify a linked marker. However, approximately 30 percent of the genome was excluded as the site of the hypothesized locus for TS. PMID- 2324062 TI - Developmental implications of changing trajectories of IQ in males with fragile X syndrome. AB - This study examined the trajectories of cognitive development in boys under the age of 21 years with fragile X syndrome. By combining information from three centers, data from 66 boys were analyzed; only children who had been tested two or more times with the same psychometric instrument at one or more year intervals were included in this study. Results demonstrated that males with fragile X syndrome show a decline in IQ scores, with the most marked declines seen during the early pubertal period. All 22 children retested during the 11- to 15-year period showed IQ declines, suggesting a slowing of development associated with the onset of puberty. Before age 10 years, males with higher (as opposed to lower) pretest IQs were more likely to decline at subsequent testings. A single etiological factor may not be sufficient to account for the observed findings, as both changes in neurobiological- and task-related factors seem implicated in the slowing intellectual development of this population. PMID- 2324063 TI - Primary prevention of conduct disorder: issues and prospects. AB - This research seeks to advance our understanding of the primary prevention of conduct disorder in three ways: (1) by illustrating how type of analysis and research design may influence our evaluation of a variable as a potential risk factor; (2) by examining the implications for primary prevention of choosing multiple risk factors for modification; and (3) by comparing the advantages and disadvantages of intervening with children living in high-risk situations versus children in the general population. The analyses are based on 1,001 children aged 6 to 12 in 1983 who participated in the original Ontario Child Health Study and follow-up. The results show that (1) inattention to type of analysis and research design may lead to false inferences about the usefulness of a hypothesized risk factor; (2) selecting multiple risk factors for modification increases the potential program benefits in prevention; and (3) primary prevention demonstration projects, to be evaluable at reasonable cost, must focus on children living in high-risk situations. PMID- 2324064 TI - Catecholamines and diagnoses in children. AB - Theoretically, noradrenergic (NA) function may be lower in subjects with undersocialized conduct disorder (CDU) and higher in subjects with anxiety/depressive disorder. To test this hypothesis, diagnostic and 24-hour urine catecholamine measures were compared between subjects with plasma dopamine beta-hydroxylase (D beta H) activities less than 6 mumoles/min/L (low D beta H group) and greater than 15 mumoles/min/L (high D beta H group). Several measures relating to norepinephrine metabolism were lower in the low D beta H group, and the low D beta H group had more diagnoses of CDU and fewer anxiety and depressive disorder diagnoses. Comparisons between clinical and biological measures within each of the D beta H groups were also consistent with the hypothesized relationship between NA function, CDU, and anxiety/depressive disorder. PMID- 2324065 TI - Aggression and counteraggression during child psychiatric hospitalization. AB - The article reports on a 1-year descriptive study of aggressive incidents and staff counteraggressive strategies within a child psychiatry inpatient unit. Ninety-nine child/adolescent patients produced a total of 887 reportable aggressive incidents during the 12-month study period. Seclusion, activity restriction, physical restraint, and administration of p.r.n. medication were studied in relation to patient aggression. Results of the study confirm the hypotheses that (1) much patient aggression within defined clinical contexts conforms to patterns of prediction directly related to person and environmental variables, and (2) the primary value of counteraggression strategies such as seclusion and restraint resides in the acute management of aggressive children and not in long-term therapeutic functions. The article offers some recommendations for new research in this general area as well as suggestions for clinical applications of these methods. PMID- 2324066 TI - Predictors of the use of seclusion on an inpatient child psychiatric unit. AB - Characteristics of 102 children admitted to a child psychiatry unit were analyzed to determine predictability of seclusion use. A subgroup of 36 children was rated using the Zeitlin Coping Inventory. Results showed that frequently secluded children were significantly more likely to have a history of physical abuse, neurological impairment, relatively weaker verbal ability, assaultive behavior, and a suicide attempt in the 6 months prior to admission. They shared a profile of coping behavior, such as more need for environment structure, less ability to successfully meet needs, and more activity and rigidity in their unsuccessful attempts. Three items on the Coping Inventory related to frustration tolerance, response to external controls, and knowledge of what is expected in situations were highly predictive of seclusion use. Results suggest that seclusion may meet specific needs for children and may not always be an indicator of inadequate institutional policies and programs. PMID- 2324067 TI - Determinants of academic achievement in children with psychiatric disorders. AB - Academic achievement within a child psychiatric sample was examined as a function of six variables: IQ, socioeconomic status, age, sex, neuropsychological status, and the severity of behavioral disturbance. As expected, the results revealed a different pattern of predictors than what is generally the case of normal school aged children. The results underscored the importance of neuropsychological factors, more than IQ and demographic variables, in understanding the academic deficits often seen in children with significant mental and emotional disturbance. PMID- 2324068 TI - Utility of the Beck Depression Inventory with clinic-referred adolescents. AB - This study reports on the utilization of the Beck Depression Inventory (BDI) and the Diagnostic Interview for Children and Adolescents (DICA) in a sample of 100 clinic referred adolescents. Results indicate that the BDI efficiently identified and differentiated depressed from nondepressed adolescents. In addition, greater levels of depressive symptomatology and depressive disorder were found in girls. Reasons for these general sex differences are discussed, and it is concluded that a psychological explanation appears more promising than existing biological explanations. PMID- 2324069 TI - The Johns Hopkins Depression Scale: normative data and validation in child psychiatry patients. AB - With a newly devised 38-item symptom checklist based upon DSM-III criteria for major affective disorder, normative data were obtained on 1,004 school children, aged 5 to 13 years. The items on the checklist were scored on a severity scale of 0 to 4 with a maximum score of 152. The average raw scores in this population was 31.2, SD +/- 2.4. Of 57 inpatients, 27 met DSM-III criteria for a major affective disorder and obtained mean raw scores of 66.8, SD +/- 13.4. The 30 nondepressed inpatients had scores of 36.4, SD +/- 5.3. The differences in the raw scores between the depressed inpatients and normal controls, and depressed and nondepressed inpatients were found to be statistically significant (p less than 0.01). The new checklist can serve as a potential screening instrument, is not time consuming, and has been standardized on a large normal control population for age and sex. PMID- 2324070 TI - Psychosocial factors associated with urban adolescent female suicide attempts. AB - This study identified psychosocial factors that differentiated 19 adolescent female suicide attempters from 21 demographically similar nonattempters in a low income, urban area. Adolescents and their parents independently completed questionnaires and participated in structured and semistructured interviews. Attempters expressed significantly higher levels of suicidal ideation and were described by their parents as displaying higher levels of depressed mood and delinquent behavior problems than nonattempters. Attempters also identified fewer support persons, were less likely to be living with their mothers, were less likely to describe confiding relationships with parents/guardians, and had less active and affectionate relationships with mother figures than nonattempters. Finally, attempters reported more undesirable life stresses than nonattempters. PMID- 2324071 TI - Bipolar disorder in a prepubescent child. AB - Early onset bipolar affective disorder (BAD) is a relatively rare psychiatric disturbance in childhood and early adolescence. Its diagnosis is difficult due to the presentation of symptoms suggestive of other psychiatric illnesses. The literature on BAD in children is reviewed with emphasis on the clinical picture, predictive factors, and pharmacotherapy. Illustrations of these points are made through the use of a case report of a boy who first presented with symptoms at age 7. PMID- 2324072 TI - School consultation: evolving issues. AB - Schools are currently facing (1) increasing demands for special services, (2) parents' expectations for academic achievement, (3) budget constraints, (4) an older faculty, and (5) a broadening mandate to nurture young children and prevent self-destructive behavior in adolescence. Whether as consultants or caring for individual children, child psychiatrists should consider these evolving issues in their work with parents and schools. PMID- 2324073 TI - Variations on the theme of conduct. PMID- 2324074 TI - What motivates infants? PMID- 2324075 TI - The masquerade of mutism. PMID- 2324076 TI - Professionalism: sane and insane. PMID- 2324077 TI - A study of the clinical efficacy of maintenance ECT. AB - Six cases of maintenance electroconvulsive treatment (ECT) in elderly patients with major mood disorders were followed for 1 to 6 years. Documented duration of illness before instituting maintenance ECT ranged from 6 to 53 years (mean +/- SD = 22 +/- 18 years). Measures of effectiveness and safety of maintenance treatment and measures of functional status were prospectively obtained during periods of outpatient ECT administration, and functional status measures were retrospectively obtained for equivalent pre-ECT periods. Such measures included mean frequency of annual hospital admissions and average annual length of inpatient stay, mean scores on standard rating instruments of global functioning and cognitive performance, the average number of prescribed psychotropic medications, and ratings of affect. Some of the authors' findings support the contention that maintenance ECT may help sustain remission in the course of affective illness. PMID- 2324078 TI - Caffeine-modified electroconvulsive therapy in depressed patients with medical illness. AB - Although pretreatment with intravenous caffeine is an effective technique for increasing seizure duration during a course of electroconvulsive therapy (ECT), little has been published regarding the use of this technique in patients with severe medical illness. The authors describe nine depressed inpatients with major cardiovascular or other medical disease or both whose ECT seizure durations declined despite maximal settings on the ECT device. In all cases, caffeine pretreatment lengthened seizures, and clinical improvement followed. The caffeine modified ECT treatments were well tolerated and were associated with no clinically significant adverse cardiovascular effects. PMID- 2324079 TI - Ganser syndrome: a case report. PMID- 2324080 TI - Reverse seasonal affective disorder in major depressive disorder. PMID- 2324081 TI - Disulfiram-induced fulminating hepatitis and monitoring guidelines. PMID- 2324082 TI - Clonazepam treatment of obsessive compulsive disorder. PMID- 2324083 TI - Chronic fatigue syndrome. PMID- 2324084 TI - Excretion of fluoxetine in human breast milk. PMID- 2324085 TI - Serotonin and its effects on human behavior. PMID- 2324086 TI - Bovine seminal plasma constituents modulate the activity of caltrin, the calcium transport regulating protein of bovine spermatozoa. AB - Adsorption of caltrin on a cation exchanger during purification transformed it from inhibitor to enhancer of calcium uptake. Ether extracts of acidified preparations of bovine seminal plasma transformed enhancer caltrin back to inhibitory caltrin; this capacity of the ether extracts was lost after incubation with an anion exchanger, indicating that anions in the extract could be responsible for the reversal of caltrin activity. Of the anions identified in the ether extract of acidified bovine seminal plasma, phosphatidylserine converted enhancer caltrin to the inhibitory form at pH 7.4. Citrate at millimolar concentrations lowered calcium uptake of sperm in the presence of enhancer caltrin to near control levels. Cardiolipin at concentrations comparable to its natural occurrence in the seminal plasma prevented enhancer caltrin from stimulating the sperm cells to take up calcium above their usual capacity. Dipalmitoylphosphatidylglycerol, phosphatidylcholine derived from bovine brain, phosphatidylethanolamine from bovine heart, and other phospholipids with transition temperatures higher than the assay temperature had no effect on the activity of enhancer caltrin, while dimyristoylphosphatidylcholine had an effect on enhancer caltrin similar to that of citrate. Phosphatidylinositol from soybean was also capable of lowering caltrin-stimulated calcium uptake in bovine sperm to control levels. Data on enhancer caltrin fluorescence in the presence of phosphatidylserine from bovine brain suggest conformational changes in the protein due to binding of the phospholipid. In comparison, the phosphatidylcholine from bovine brain appeared not to alter enhancer caltrin. PMID- 2324087 TI - Translational regulation of complement protein C2 expression by differential utilization of the 5'-untranslated region of mRNA. AB - A recently isolated cDNA for human complement protein C2, C2HL5-3, has an unusually long 5'-untranslated region (UTR) containing four open reading frames upstream of the authentic initiation codon. Here we report that deletion of the 5'-UTR of C2HL5-3 resulted in a 10-fold enhancement in the translational efficiency of C2 in transient eukaryotic cellular assays. Elimination of the open reading frames in the 5'-UTR by site-directed mutagenesis of the initiation codons did not affect C2 synthesis in this assay system, indicating that other structural elements in this region are responsible for translational control. We also show that several C2 mRNAs of varying length in the 5'-UTR, including an alternative C2 mRNA expressing a considerably shorter 5'-UTR, are present in the liver and that the shorter C2 mRNA is the only C2 message found in U937 cells. These results suggest that tissue-specific utilization of alternative transcriptional start sites results in differential translational efficiencies of C2 and may provide insights into the tissue- and stimulus-specific regulation of eukaryotic gene expression. PMID- 2324088 TI - Structure of wheat serine carboxypeptidase II at 3.5-A resolution. A new class of serine proteinase. AB - The structure of serine carboxypeptidase II from wheat bran has been determined to 3.5-A resolution by multiple isomorphous replacement, solvent flattening, and crystallographic refinement. The amino acid sequence has been fit to the electron density map and the model refined to a conventional crystallographic R factor of 20.9%. The molecule is an alpha + beta protein and contains a "catalytic triad" (Asp338, His397, and Ser146) similar in arrangement to those in chymotrypsin and subtilisin. The -fold of the polypeptide backbone is, however, completely different from those enzymes. This suggests that this is a third example of convergent evolution to a common enzymatic mechanism. The -fold is, on the other hand, surprisingly similar to that of the zinc proteinase carboxypeptidase A. PMID- 2324089 TI - A ubiquitin-protein ligase specific for type III protein substrates. AB - A previously studied species of ubiquitin-protein ligase contains specific sites for the binding of basic (Type I) and bulky hydrophobic (Type II) NH2-terminal amino acid residues of protein substrates. We now describe another enzyme that ligates ubiquitin specifically to proteins that have NH2-terminal residues other than the above two categories (Type III substrates). The new species of ligase, that we call E3 beta, is separable from the formerly described ligase (termed E3 alpha) by affinity chromatography on protein substrate columns. E3 beta was partially purified from extracts of rabbit reticulocytes and was shown to be required for the breakdown of Type III proteins. Apart from its different substrate specificity, it resembles E3 alpha in some physical properties, in a requirement for ubiquitin carrier protein (E2) for conjugate formation, and in its action to ligate multiple ubiquitin units to the substrate protein. The denatured derivative of bovine pancreatic ribonuclease is a specific substrate for E3 alpha, while that of ribonuclease S-protein is a good substrate for E3 beta. Since S-protein is formed by the removal from ribonuclease of NH2-terminal S-peptide, it is suggested that E3 beta interacts with an NH2-terminal determinant exposed in ribonuclease S-protein. PMID- 2324090 TI - Functional identity of a primer recognition protein as phosphoglycerate kinase. AB - Primer recognition proteins (PRP) are cofactors of DNA polymerase alpha and may have a role in lagging strand DNA replication. Purified PRP from HeLa cells and human placenta are composed of two subunits of 36,000 (PRP 1) and 41,000 (PRP 2) daltons. Upon tryptic digestion, amino acid sequencing of tryptic peptides, and homology search against a protein sequence data base, we have identified PRP 2 to be the glycolytic enzyme, phosphoglycerate kinase (PGK). The activities of PRP and PGK increase coordinately in the PRP purification procedure. PRP activity is inhibited by the PGK substrate 3-phosphoglycerate and the competitive inhibitor of substrate binding, DL-alpha-glycerol 3-phosphate. 5'-p-Fluorosulfonylbenzoyl adenosine, which inactivates PGK by binding to the nucleotide binding site, also inhibits PRP. For PRP activity, the two substrate binding sites of PGK are necessary in addition to the as yet unidentified PRP 1 polypeptide. PMID- 2324091 TI - Isolation and characterization of the human hepatic lipase gene. AB - Overlapping bacterial phage and cosmid genomic clones were isolated spanning an area of approximately 60 kilobases that contains the human hepatic lipase (HL) gene. It is composed of 9 exons spanning approximately 35 kilobases of DNA. The entire coding regions, the 5'-flanking sequences, and the exon-intron junctions were sequenced. The intron positions correspond to those of human lipoprotein lipase and canine pancreatic lipase, supporting the concept that these genes constitute a dispersed gene family of lipases and have evolved by duplication of a common ancestral gene. A region of the HL gene, which displays a significant homology with various other lipolytic enzymes and contains the putative catalytic site serine residue of HL, was encoded by exon 4. A major transcription start site of the human HL gene was located by primer extension analysis, 43 nucleotides upstream of the translation initiation codon. Two possible promoter elements were located 25 and 63 nucleotides upstream of the transcription initiation site: a "TATA" box-like sequence, TAATA, and a sequence found in the promoter region of many liver-specific genes, AGGTTAATTATTAAT. In addition, sequences homologous to glucocorticoid and cAMP-responsive elements were identified in the 5'-nontranscribed region. PMID- 2324092 TI - A cloned ATP:guanidino kinase in the trematode Schistosoma mansoni has a novel duplicated structure. AB - Creatine kinase (CK) is part of a conserved family of ATP:guanidino phosphotransferases whose members play important roles in intracellular energy flow. Previously characterized members of this family are approximately 80-kDa dimers of two related 40-kDa subunits. We have cloned a gene from the parasitic trematode Schistosoma mansoni which has substantial amino acid sequence similarities to CK. Like the genes for vertebrate CKs, this gene is developmentally regulated; mRNA levels are high in the infective cercarial stage but rapidly decrease upon transformation to the parasitic schistosomulum stage. In contrast to members of the guanidino phosphotransferase family characterized previously, however, the schistosome gene appears to be a direct fusion of two CK like domains that encode a single 74-kDa polypeptide. Correlative evidence from enzyme assays of crude parasite homogenates suggests that the cloned gene is a creatine kinase. This represents the first molecular cloning of an invertebrate ATP:guanidino phosphotransferase. PMID- 2324093 TI - Cross-linking site in Azotobacter vinelandii complex. AB - The Fe-protein and the MoFe-protein of the Azotobacter vinelandii nitrogenase complex can be chemically cross-linked by 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide (Willing, A., Georgiadis, M.M., Rees, D. C., and Howard, J. B. (1989) J. Biol. Chem. 264, 8499-8503). In this reaction, one of the identical subunits of the Fe-protein dimer is linked by an isopeptide bond to each beta-subunit of the MoFe-protein tetramer. The reaction has been found to be highly specific with greater than 85% of amino acid residues Glu-112 (Fe-protein) and Lys-399 (MoFe-protein) cross-linked to each other. Although Glu-112 is located in a highly conserved amino acid sequence, it is found in only half of the known Fe-protein sequences. Likewise, Lys-399 is not a conserved residue in the MoFe-protein. Glu-112 appears to be part of an anionic cluster of nine carboxylic acids which is located between the proposed thiol ligands for the Fe:S center. In contrast, the basic residue cluster which includes Lys-399 has been found in only in the Azotobacter MoFe-protein. Thus, this crosslinking reaction either is unique to Azotobacter nitrogenase or must involve other residues in the MoFe-protein of other species. Because Lys-399 and Glu-112 form a specific cross link, it is probable that they are part of the interaction site leading to productive complex formation. This information should be useful for the model building of the complex from the crystallographic structures of the individual components. PMID- 2324094 TI - L-lactate 2-monooxygenase from Mycobacterium smegmatis. Cloning, nucleotide sequence, and primary structure homology within an enzyme family. AB - L-Lactate 2-monooxygenase catalyzes the oxidation of L-lactate to acetate and carbon dioxide. The catalytic mechanism has been extensively investigated but very little is known about which amino acid residues may play a role in catalysis. As a first step toward this goal, the gene for this protein from Mycobacterium smegmatis has been cloned and sequenced. Peptide sequencing data for L-lactate 2-monooxygenase was used to construct three sets of fully redundant tetradecamer oligonucleotide probes, which were hybridized to restriction digested M. smegmatis DNA. An approximately 3-kilobase pair PstI fragment hybridized with two of the probes. This region was subsequently isolated and cloned into Escherichia coli. From this size-fractionated gene bank, a 3.1 kilobase pair genomic DNA fragment was isolated by colony hybridization to two of the oligonucleotide probes. The complete gene for L-lactate 2-monooxygenase was contained on this fragment as shown by DNA sequencing of the whole insert. The DNA sequence codes for a mature protein that is 393 amino acids in length with a subunit molecular weight of 43,072 (including the FMN). The protein sequence shows impressive homology with the primary structures of two mechanistically related proteins, yeast flavocytochrome b2 (Lederer, F., Cortial, S., Becam, A. M., Haumont, P.-Y., and Perez, L. (1985) Eur. J. Biochem. 152, 419-428; Guiard, B. (1985) EMBO J. 4, 3265-3272) and spinach glycolate oxidase (Volkita, M., and Somerville, C. R. (1987) J. Biol. Chem. 262, 15825-15828; Cederlund, E., Lindqvist, Y., Soderlund, G., Branden, C.-I., and Jornvall, H. (1988) Eur. J. Biochem. 173, 523-530). For each residue proposed from the crystal structure of glycolate oxidase to be involved in catalysis (Lindqvist, Y., and Branden, C.-I. (1989) J. Biol. Chem. 264, 3624-3628), an identical residue was found in a homologous position in lactate oxidase. Furthermore, most of these residues occur in regions whose sequences are highly conserved between lactate oxidase, flavocytochrome b2, and glycolate oxidase. PMID- 2324095 TI - Positive and negative regulation of a tumor necrosis factor response in melanoma cells. AB - Tumor necrosis factor (TNF) elicits a wide variety of responses in target cells by binding to cell surface receptors, but the signal transduced from these receptors in unclear. We examined the role of two different second messenger systems in the regulation of plasminogen activator inhibitor, type 2 (PAI-2) induction by TNF in SK-MEL-109 melanoma cells. Synthesis of PAI-2 and transcription of its mRNA could be induced by a protein kinase C (PKC) activator, phorbol myristate acetate. In addition, induction of PAI-2 synthesis by TNF was blocked by two PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl)-2 methylpiperazine dihydrochloride. The inhibitor of cyclic nucleotide-dependent protein kinases, N-[2-(methylamino)-ethyl]-5-isoquinoline sulfonamide dihydrochloride, was much less effective in decreasing PAI-2 synthesis. Staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride also inhibited both TNF- and phorbol myristate acetate-induced PAI-2 mRNA accumulation. We measured the binding of 3H-labeled phorbol dibutyrate to membrane and cytosol fractions of TNF-treated SK-MEL-109 cells and found a transient redistribution of 3H-labeled phorbol dibutyrate binding from cytosol to membrane fractions in response to TNF. In contrast to the positive regulation by PKC in promoting TNF-induced PAI-2 synthesis cAMP inhibited this response. Pretreatment of cells with agents that raise intracellular cAMP levels completely abolished TNF-induced PAI-2 synthesis. Addition of cAMP-elevating agents during TNF induction could also block PAI-2 synthesis. PAI-2 mRNA accumulation in response to TNF was inhibited, but not completely abolished, by cAMP-elevating agents, suggesting that cAMP also exerted its inhibitory effect at the translation level. The positive regulation of a TNF response by PKC and its negative modulation by cAMP may provide a means for intracellular coordination of signals from interacting extracellular factors in regulating TNF responses in different target cells. PMID- 2324096 TI - Two silencers regulate the tissue-specific expression of the collagen II gene. AB - Collagen II, the major component of cartilage, is synthesized primarily by chondrocytes and by certain cells in the eye. Previously, we have studied the regulatory regions of the collagen II gene by DNA transfection assays (Horton, W., Miyashita, T., Kohno, K., and Yamada, Y. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8864-8868). These studies show that both the promoter and an enhancer sequence in the first intron are required for high transcriptional activity in chondrocytes. These elements do not show significant activity in cells which do not synthesize collagen II, such as in muscle cells and fibroblasts. In this report, we have constructed plasmids containing various deletions of the promoter of the collagen II gene, fused to a reporter gene for chloramphenicol acetyltransferase (CAT) and transfected them into both chick embryonic fibroblasts and HeLa cells. We have found that silencer elements in the collagen II promoter region reduce CAT activity 11-fold in fibroblasts, while not affecting the enhancer-mediated transcription in chondrocytes. Deletions in the promoter showed that most of the silencing activity was localized in two sites, between -360 and -460 base pairs and between -620 and -700 base pairs. Furthermore, a fragment containing these two sequences in a thymidine kinase promoter CAT construct reduced the activity of the promoter in an orientation independent fashion. Sequence analysis revealed that the two silencer regions are homologous and contain consensus motifs for silencer elements found in other genes. Gel retardation experiments showed that nuclear factors from HeLa cells bind specifically to a DNA fragment containing the silencer, whereas chondrocyte nuclear extracts did not show any activity. Thus, our study indicates that the expression of the collagen II gene is controlled by both negative and positive elements to ensure that the gene is only expressed in suitable cells. PMID- 2324097 TI - Mobilization of iron from endocytic vesicles. The effects of acidification and reduction. AB - The factors necessary to dissociate iron from transferrin in endocytic vesicles and to mobilize the iron across the vesicle membrane were studied in a preparation of endocytic vesicles markedly enriched in transferrin-transferrin receptor complexes isolated from rabbit reticulocytes. Vesicles were prepared with essentially fully saturated transferrin by incubating the reticulocytes with the protonophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone prior to incubation with 59Fe, 125I-transferrin with or without fluorescein isothiocyanate labeling. Initiation of acidification by the addition of ATP was sufficient to achieve dissociation of 59Fe from transferrin with a rate constant of 0.054 +/- 0.06 s-1. Mobilization of 59Fe out of the vesicles required, besides ATP, the addition of a reductant with 1 mM ascorbate, allowing approximately 60% mobilization at 10 min with a rate constant of 0.0038 +/- 0.0006 s-1. An NADH:ferricyanide reductase activity could be demonstrated in the vesicles with an activity of 7.1 x 10(-9) mol of NADH reduced per min/mg of vesicle protein. Both dissociation and mobilization were inhibited by N-ethylmaleimide, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and monensin. Mobilization, but not dissociation, was inhibited by the permeant Fe(II) chelator alpha,alpha' dipyridyl. The Fe(III) chelators deferoxamine, diethylenetriaminepentaacetic acid, and apotransferrin did not promote mobilization of dissociated iron in the absence of a reductant. This study establishes the basis for the cellular incorporation of iron through the endocytic pathway in which the endocytic vesicle membrane utilizes, in a sequential way, an acidification system, an iron reduction system, and an Fe(II) transporter system. PMID- 2324098 TI - Formation of prostaglandin A analogues via an allene oxide. AB - One potential biosynthetic route to the prostaglandins involves the participation of lipoxygenase and allene oxide synthase enzymes, giving a hydroxylated allene oxide, which then might cyclize to form prostaglandin A or a close analogue. We have tested a model of this type of transformation using 8-hydroxy-15S hydroperoxy eicosanoids as substrates for the dehydrase (allene oxide synthase) in flaxseed. Four of these substrates, each with a 9E,11Z,13E-conjugated triene, gave an observable rate of reaction. The two derived from eicosapentaenoic acid reacted more rapidly than the corresponding arachidonic acid analogues. Also, the 8S-hydroxy-15S-hydroperoxy diastereomers reacted more rapidly than their 8R hydroxy analogues. Products were characterized by high pressure liquid chromatography, UV, gas chromatography-mass specrometry, 1H NMR, and CD. Reaction of the (8S)-hydroxy-(15S)-hydroperoxy-eicosapentaenoic acid gave two alpha-ketols [8S),15-dihydroxy-14-oxoeicosa-5Z,9E,11Z,17Z+ ++-tetraenoic acid and the corresponding 11E isomer in a 2:1 ratio), together with four prostaglandin A3 analogues which differed in the configurations of the side chains. Oxygen 18 labeling fully supported the intermediacy of an allene oxide in the biosynthesis. The corresponding "8R" substrate was converted to the enantiomers of these products plus three 13-hydroxy-14,15-epoxy derivatives. The arachidonate analogues formed the epoxy-hydroxy derivatives, the alpha-ketols, and two prostaglandin A2 analogues with trans configuration of the side chains. These results demonstrate (i) a feasible route of metabolism of lipoxygenase products to hydroxy allene oxide, (ii) the potential for the resulting allene oxide to cyclize to a prostaglandin A analogue, and (iii) the marked influence of the hydroxyl configuration of the rate of reaction and resulting profile of products. Some of these reactions may occur in a natural pathway of prostanoid biosynthesis in corals and other organisms. PMID- 2324099 TI - RNA editing of apolipoprotein B mRNA. Sequence specificity determined by in vitro coupled transcription editing. AB - Apolipoprotein (apo) B-48 mRNA is produced by in vivo RNA editing which involves a C----U conversion of the first base of the codon CAA for Gln-2153, changing it to UAA, an in-frame stop codon. We have reproduced the editing reaction in vitro using nuclear extracts. Efficient RNA editing was demonstrated by using apoB mRNA segments as substrate or in a coupled transcription-editing reaction using apoB minigenes as template. ApoB minigenes were constructed by ligating the adenovirus major late promoter to a fragment of apoB-100 DNA containing the editing site and used for the transcription-editing reaction. We defined the sequence specificity of the editing reaction using site-specific single and multiple base mutants constructed by the polymerase chain reaction. Among 22 different mutant apoB-100 minigene constructs containing mutations in the bases immediately flanking the edited C-6666, 20 were edited in the coupled transcription-editing reaction. The results suggest a relatively lax sequence specificity for apoB mRNA editing. Our observation may have important implications for apoB-48 biogenesis as well as for the editing process as a general biologic regulatory mechanism. PMID- 2324100 TI - Analyses of catalytic activity and inhibitor binding of human acid beta glucosidase by site-directed mutagenesis. Identification of residues critical to catalysis and evidence for causality of two Ashkenazi Jewish Gaucher disease type 1 mutations. AB - Analyses of catalytic properties and inhibitor binding were conducted to investigate the molecular basis of active site function of human acid beta glucosidases (EC 3.2.1.45) expressed from normal and Gaucher disease Type 1 alleles. Comparative studies were conducted with enzymes expressed from natural (spleen and fibroblasts) alleles or from mutagenized cDNAs in Spodoptera frugiperda (Sf9) cells using the baculovirus expression system. Mutant cDNAs containing Thr43 to Lys43 (beta-GlcThr43----Lys) and Asp358 to Glu358 (beta GlcAsp358----Glu) substitutions and two cDNAs containing Ashkenazi Jewish Gaucher disease Type 1 mutations, Arg120 to Gln120 (beta-GlcArg120----Gln) and Asn370 to Ser370 (beta-GlcAsn370----Ser) were expressed and the gene products characterized by enzymatic, immunologic, and inhibitor studies. Genotypes at the acid beta glucosidase locus in selected Gaucher disease Type 1 patients were determined by allele-specific oligonucleotide hybridization of amplified genomic DNA. Compared with normal, recombinant or natural enzymes expressed from beta-GlcAsn370----Ser alleles had about 2-5-fold decreased specific activity based on CRIM (cross reacting immunologic material). The beta-GlcArg120----Gln cDNA expressed catalytically inactive CRIM in Sf9; consistent with the 9-fold decreased CRIM specific activity of the natural enzyme from a beta-GlcArg120----Gln/beta GlcAsn370----Ser genetic compound. The beta-GlcAsp358----Glu cDNA expressed catalytically inactive CRIM in Sf9 cells. The presence of natural or recombinant enzyme expressed from beta-GlcAsn370----Ser alleles was sufficient to confer 3-5 fold increased IC50 values for deoxynojirimycin, glucosylsphingosine, and N-alkyl glucosylamine derivatives. Progress curves for inhibition by the slow-tight binding N-alkyl-glucosylamines indicated that the beta-Glc-Asn370----Ser mutation did not alter a conformational change induced by these reaction intermediate analogues. These results provide evidence that the beta-GlcArg120----Gln and beta GlcAsn370----Ser mutations found in Gaucher disease Type 1 patient genomes are the molecular bases of the enzymatic dysfunction. In addition, the region including Arg120 and that encompassing Asp358 and Asn370 contain residues critical to active site formation or participation in the catalytic mechanism. PMID- 2324101 TI - Purification and structure of caltrin-like proteins from seminal vesicle of the guinea pig. AB - Two different small proteins that cross-react with the antiserum against bovine caltrin (calcium transport inhibitor) have been purified from the seminal vesicle contents of the guinea pig. The primary structure and some molecular characteristics of the pure proteins are reported. The two proteins interact with concanavalin A indicating the presence of carbohydrates in their molecules. Chemical deglycosylation with trifluoromethanesulfonic acid, after reduction and carboxymethylation, results in complete loss of affinity for the lectin. Removal of sugar components from the structure destroys the ability of caltrin-like proteins to react with antibodies to bovine caltrin. The protein moving faster on polyacrylamide gel electrophoresis is designated guinea pig caltrin I, the other is II. They contain 45 and 55 amino acids, and the molecular weights of the peptide portions are 5082 and 6255, respectively. Although they have entirely different amino acid sequences, they share some common features: recognition by rabbit antibodies to bovine caltrin, the predominance of basic residues and the presence of 3 cysteine residues in fraction I and 8 in fraction II. The proteins have pI values of 9.5 and 10.2, respectively, which are consistent with the amino acid composition. The two pure fractions are approximately equally effective, on a weight basis, as inhibitors of 45Ca2+ uptake by guinea pig spermatozoa. The data presented reinforce the hypothesis that caltrin-like proteins are responsible for the previously reported (Coronel, C.E., San Agustin, J., and Lardy, H.A. (1988) Biol. Reprod. 38, 713-722), calcium-transport inhibitor activity detected in reproductive tract fluid from adult male guinea pigs. PMID- 2324102 TI - Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans. AB - The structure of human syndecan, an integral membrane proteoglycan, has been determined by cloning its full-length cDNA, which codes for the entire 310-amino acid-long core protein, including the NH2-terminal signal peptide. Similar to mouse syndecan (Saunders, S., Jalkanen, M., O'Farrell, S., and Bernfield, M. (1989) J. Cell Biol. 108, 1547-1556), the core protein of human syndecan can be divided into three domains: a matrix-interacting ectodomain containing putative glycosaminoglycan attachment sites, a 25-residue hydrophobic membrane-spanning domain, and a 34-residue cytoplasmic domain. Several interesting conserved structures were revealed by comparing the human syndecan sequence to the murine one. (i) Although the ectodomains are only 70% identical, all putative glycosaminoglycan attachment sites are identical (two of them belong to the consensus sequence SGXG and three others to (E/D)GSG(E/D), as are also (ii) the single putative N-glycosylation site and (iii) the proteinase-sensitive dibasic RK site adjacent to the extracellular face of the transmembrane domain. Furthermore, (iv) the transmembrane domain is 96% identical, as the only change in human syndecan was an alteration of an alanine residue to glycine; and finally, (v) the cytoplasmic domain is 100% identical, including 3 identically located tyrosine residues. Comparison of transmembrane and cytoplasmic domains to a third cell-surface proteoglycan, 48K5 from human lung fibroblasts (Marynen, P., Zhang, J., Cassiman, J., Vanden Berghe, H., and David, C. (1989) J. Biol. Chem. 264, 7017-7024), indicates that the transmembrane and cytoplasmic domains are similar also in this molecule regardless of the presence of a totally nonhomologous ectodomain. Thus, the transmembrane and cytoplasmic domains are unique for these cell-surface proteoglycans, which we propose to be members of a novel gene family of syndecans. PMID- 2324103 TI - Organization and expression of the Drosophila Phe-Met-Arg-Phe-NH2 neuropeptide gene. AB - We have studied a Drosophila gene that encodes multiple neuropeptides related to Phe-Met-Arg-Phe-NH2 (FMRFamide). Using a combination of genomic sequencing, Northern blot analysis, primer extensions, and nuclease protection assays, we have described its organization and expression. The results indicate that this Drosophila neuropeptide gene contains two exons separated by an intron of approximately 2.5 kilobase pairs, and that its expression is limited to a single predominant RNA species of approximately 1.7 kilobases. The FMRFamide gene contains a 5' untranslated region that is 106 nucleotides long and is encoded in its entirety by exon I. The open reading frame (encoding a 347-amino acid neuropeptide precursor) begins with the first nucleotide of exon II. PMID- 2324104 TI - Cloning, characterization, and expression of the gene for the catalytic subunit of cAMP-dependent protein kinase in Caenorhabditis elegans. Identification of highly conserved and unique isoforms generated by alternative splicing. AB - The nematode Caenorhabditis elegans expresses substantial amounts of several forms (Mr values = 39,000-41,000) of the catalytic subunit (C) of cAMP-dependent protein kinase. Approximately 65% of the total cAMP-dependent phosphotransferase activity is recovered in particulate fractions of homogenates prepared from asynchronous populations of C. elegans. The C subunit is expressed at a low level in cytosolic and particulate compartments during embryogenesis. As the nematodes progress from late embryonic stages to the newly hatched, first larval (L1) stage, C subunit content increases 15-fold. High levels of C subunits are observed in several subsequent larval and adult stages of development. Since the relative abundance of C subunit mRNA changes little with development, it appears that control of C expression is exerted the translational and/or post translational levels. cDNAs for two types of C have been cloned and sequenced. The derived amino acid sequence of a major isoform (CeCAT alpha, 358 residues) is highly homologous (82% identical) with the murine C alpha subunit. A second, novel C subunit (CeCAT alpha', 374 residues) has a unique 56-residue carboxyl terminal region that is generated by the alternative splicing of the C pre-mRNA. The splicing process that yields CeCAT alpha' is unusual because it converts the central portion of an apparent 1-kilobase (kb) intron to an exon. The alternative exon introduces the novel carboxyl terminus and a new translation stop signal, while simultaneously converting the coding sequence for 40 carboxyl-terminal residues in CeCAT alpha into 3'-untranslated nucleotides. The 5' end of the C. elegans C subunit mRNA is produced by the trans-splicing of the C gene transcript to a 22-base pair C. elegans leader sequence originally described by Krause, M., and Hirsh, D. [1987) Cell 49, 753-761). The 20-kb C. elegans C gene is divided into seven exons by introns ranging in size from 54 to 8000 bp. The sizes of the C. elegans C subunit gene, cytoplasmic mRNA (2.5 kb), and subunit protein are similar to the sizes of the murine C alpha gene, mRNA, and polypeptide. However, the nematode and murine C genes differ significantly in the organization of their introns and exons. PMID- 2324105 TI - Separate nuclear genes encode sarcomere-specific and ubiquitous human mitochondrial creatine kinase isoenzymes. AB - Creatine kinase (EC 2.7.3.2) isoenzymes play a central role in energy transduction. Nuclear genes encode creatine kinase subunits from muscle, brain, and mitochondria (MtCK). We have recently isolated a cDNA clone encoding MtCK from a human placental library which is expressed in many human tissues (Haas, R. C., Korenfeld, C., Zhang, Z., Perryman, B., Roman, D., and Strauss, A. W. (1989) J. Biol. Chem. 264, 2890-2897). With nontranslated and coding region probes, we demonstrated by RNA blot analysis that the MtCK mRNA in sarcomeric muscle is distinct from this placenta-derived, ubiquitous MtCK cDNA. To compare these different mRNAs, a MtCK cDNA clone was isolated from a human heart library and characterized by complete nucleotide sequence analysis. The chemically determined NH2-terminal 26 residues of purified human heart MtCK protein are identical to those predicted from this sarcomeric MtCK cDNA. The human sarcomeric and ubiquitous cDNAs share 73% nucleotide and 80% predicted amino acid sequence identities, but have less than 66% identity with the cytosolic creatine kinases. The sarcomeric MtCK cDNA encodes a 419-amino acid protein which contains a 39 residue transit peptide essential for mitochondrial import. Primer extension analysis predicts a 348-base pair 5'-nontranslated region. RNA blot analysis demonstrates that heart-derived MtCK is sarcomere-specific, but the ubiquitous MtCK mRNA is expressed in most tissues. Thus, separate nuclear genes encode two closely related, tissue-specific isoenzymes of MtCK. Our finding that multiple genes encode different mitochondrial protein isoenzymes is rare. PMID- 2324106 TI - Preliminary crystallographic examination of a novel fungal lysozyme from Chalaropsis. AB - The lysozyme from the fungus of the Chalaropsis species has been crystallized. This lysozyme (Mr 22,415) displays no sequence homology with avian, phage, or mammalian lysozymes, however, preliminary studies indicate significant sequence homology with the bacterial lysozyme from Streptomyces. Both enzymes are unusual in possessing beta-1,4-N-acetylmuramidase and beta-1,4-N,6-O-diacetylmuramidase activity. The crystals grow from solutions of ammonium sulfate during growth periods from several months to a year. The space group is P2(1)2(1)2(1) with a = 34.0 A, b = 42.6 A, c = 122.1 A. Preliminary data indicate that there is 1 molecule/asymmetric unit. A complete native data set has been collected to 2.57-A resolution. The crystals are highly ordered and exhibit diffraction patterns to d spacings less than 1.5 A. PMID- 2324107 TI - The tryptic activation pathway of monomeric procarboxypeptidase A. AB - Procarboxypeptidases are the remaining major digestive zymogens the activation process of which remains unsolved. Here it is shown that in the tryptic activation of monomeric procarboxypeptidase A from porcine pancreas, the generation of carboxypeptidase A (CPA) activity parallels the limited proteolysis of the 94-residue activation segment. This degradation proceeds from the COOH terminal end of the molecule, and CPA itself makes an important and unexpected contribution by excising the COOH-terminal arginine residue of the released primary activation fragment. Successive cleavages at some of the peptide bonds of the activation segment nearest to the COOH terminus were found to be of prime importance in eliciting CPA activity, particularly those involving the carbonyl groups of Arg94 and Gly93 which were first cleaved. It is also shown that the rate of activation does not depend directly upon the generation of CPA-alpha and its conversion to CPA-beta. PMID- 2324108 TI - Occurrence in chick embryo vitreous humor of a type IX collagen proteoglycan with an extraordinarily large chondroitin sulfate chain and short alpha 1 polypeptide. AB - We have prepared a high buoyant density proteoglycan fraction from the vitreous humor of 13-day-old chick embryos. Using immunoblot analysis coupled with chondroitinase digestion, we demonstrate that the purified preparation is composed predominantly of type IX collagen-like chondroitin sulfate proteoglycan with an alpha 1(IX) chain Mr approximately 23,000 shorter than the known alpha 1 in cartilage type IX. Also different from cartilage type IX is the size of the chondroitin sulfate chain attached to the alpha 2(IX) polypeptide; its Mr is approximately 350,000 indicating that it is approximately 10 times larger in vitreous humor than in cartilage. Examination of vitreous bodies at different developmental stages indicates that a transition occurs in the size of alpha 1(IX) in a well defined temporal pattern; at about stage 31, a cartilage-type alpha 1(IX) of Mr 84,000 is the predominant species, whereas at stage 36 and thereafter, a Mr 61,000 species appears with a concomitant disappearance of the Mr 84,000 species. Immunostaining for type IX collagen followed by electron microscopic observation of 13-day-old chick embryo vitreous humor reveals a regular D-periodic arrangement of vitreous type IX collagen proteoglycan along thin fibrils. It seems possible that the chondroitin sulfate chains of extraordinarily high viscosity and high molecular weight may extend away from the fibrils, thus contributing to structural as well as functional properties of this unique matrix. PMID- 2324109 TI - Determinants of the interaction between the iron-responsive element-binding protein and its binding site in rat L-ferritin mRNA. AB - Ferritin messenger RNA has been shown to be translationally inactivated by the binding of a cytosolic protein to a 28-nucleotide iron-responsive element (IRE) located in the 5'-untranslated region of the mRNA. This interaction has been studied using quantitative receptor-ligand binding methods with gel retardation and nitrocellulose filter binding assays for the separation of bound complex from free RNA. In competition assays the entire 5'-untranslated region and the isolated IRE bound identically. The specificity of the RNA binding was studied using IRE variants. Two IREs from transferrin receptor mRNA and several variants with single base substitutions in the stem or loop had similar affinities. RNAs which could not form a stem-loop structure bound 1000-fold less well. These studies demonstrate the importance of the RNA conformation and the relative insensitivity of binding to much of the primary sequence. Saturation assays with increasing concentrations of 32P-IRE resulted in a binding hyperbola characteristic of mass action binding to a single class of sites with a KD = 0.09 nM. At 37 degrees C the dissociation rate is 0.04 min-1 (t 1/2 = 17 min). This rate is fast enough to account for the shift of ferritin RNA from the ribonucleoprotein pool to polysomes after rats are injected with iron. Determination of the concentration of the repressor requires accounting for three interconverting pools: free active repressor, mRNA-bound protein, and inactive (low affinity) repressor. Rat liver cytosol has a concentration of free active repressor of about 1 pmol/mg protein. Protein bound to endogenous mRNA can be measured by pretreatment with micrococcal nuclease or by separation with DEAE Sepharose chromatography; it is present at a level similar to that of the free active protein. Inclusion of high levels of thiol reductants in the binding incubations reduces the inactive or low affinity repressor, forming unstably activated protein which has the same KD as the endogenous active protein; this inactive or low affinity protein is 2-4 times more abundant. A mechanism for iron regulation is proposed which accounts for the kinetics, the multiple protein pools, and the characteristics of the protein in these pools. PMID- 2324110 TI - Identification of a growth hormone gene promoter repressor element and its cognate double- and single-stranded DNA-binding proteins. AB - In previous investigations, cell fusion was found to silence either the endogenous rat growth hormone (GH) gene or a transfected rat GH gene promoter, implying that repression plays a role in regulation of this gene. To search the rat GH gene promoter for repressor sequences, a series of 5'-deleted GH-CAT constructs was analyzed by transient expression in GH3 rat pituitary cells. Deletion of either a distal region between positions -307/-244 or a proximal sequence between -169/-152 increased CAT enzymatic activity by 3-4-fold. Since the action of the proximal repressor element (PRE) at -169/-152 was serum independent, and the element is located between two strong positive elements, the PRE and its cognate binding proteins were further analyzed. A 5-base pair sequence centered at -163 is critical for PRE repressor activity, since mutation of this sequence in GH-CAT constructs yielded 6-11-fold increases in expression in GH3 cells. Although the PRE is adjacent to the GH thyroid hormone (T3) response region, they are distinct elements, since the PRE mutation has little effect on the T3 response of GH-CAT constructs. Nuclear extracts of 10 cell lines were searched by DNA mobility shift for protein(s) binding specifically to a double-stranded PRE probe. No such protein was detected in any of four rodent pituitary cell lines or three human cell lines. However, three different rodent non-pituitary cell lines yielded a common shifted band, corresponding to a DNA sequence-specific PRE-binding protein (PREB). Similar analysis with the coding strand of the PRE detected no shifted band in any of these cell lines. However, the PRE noncoding strand yielded a common shifted band in all of the cell lines, corresponding to a ubiquitous, strand-specific, single-stranded PRE-binding protein (ssPREB). Mutation of the PRE permitted ssPREB binding to the coding strand, implying that the wild-type coding strand somehow excludes ssPREB binding. That PREB and ssPREB are distinct proteins was confirmed by the inability of their DNA binding sites to cross-compete binding of the proteins. PMID- 2324111 TI - Phytochrome from the green alga Mesotaenium caldariorum. Purification and preliminary characterization. AB - A method to purify the phytochrome photoreceptor from the unicellular green alga Mesotaenium caldariorum is presented. Preparative scale formation of algal protoplasts and controlled osmotic cell lysis have permitted separation of intact organelles from the phytochrome-enriched soluble protein fraction. We have utilized the observation that red light-absorbing (Pr) and far-red light absorbing (Pfr) forms of phytochrome are differentially retained on an anion exchange matrix to purify M. caldariorum phytochrome to apparent homogeneity. M. caldariorum phytochrome preparations with A650/A280 ratios greater than 0.78 exhibit a single 120-kDa band on silver-stained sodium dodecyl sulfate polyacrylamide gels. Immunoblot analyses using a cross-reactive pea phytochrome monoclonal antibody reveal that 1) the 120-kDa band represents the full-length polypeptide, 2) phytochrome is predominantly localized in the algal cytoplasm, and 3) there are 150,000-250,000 phytochrome molecules/cell. Steric exclusion high pressure liquid chromatography analysis under nondenaturing conditions indicates that M. caldariorum phytochrome has an apparent mass of 355 kDa. The absorption maxima for Pr and Pfr are 650 and 722 nm, respectively. Both are blue shifted compared with those of phytochromes from dark-grown angiosperm tissue. The molar absorption coefficient for Pr at 650 nm is 86,800 +/- 2800 liter mol-1 cm-1, which is lower than that of higher plant phytochromes. The significance of the similarities and differences of the molecular properties of phytochromes from M. caldariorum and higher plant sources is discussed. PMID- 2324112 TI - Cloning of a fibrillar collagen gene expressed in the mesenchymal cells of the developing sea urchin embryo. AB - We have cloned and characterized several overlapping cDNAs that specify a large portion of a Paracentrotus lividus fibrillar collagen molecule. Our conclusions are based on sequencing data, which showed that the clones code for a 786-amino acid collagenous domain composed of an uninterrupted series of Gly-X-Y repeats and for a 265-amino acid carboxyl-terminal globular extension. The latter domain exhibits features highly reminiscent of those of the vertebrate counterparts, notably a putative carboxyl-peptidase cleavage site, a series of similarly arranged cysteinyl residues, and an N-linked glycosylation attachment site. In situ and Northern blot hybridizations have established the size, time of appearance, and tissue localization of the collagen mRNA during sea urchin development. The collagen transcript, 9 kilobases in length, is first detected in the primary and, more predominantly, in the secondary mesenchyme cells of late gastrulae where it progressively accumulates thereafter. This and other work (D'Alessio, M., Ramirez, F., Suzuki, H.R., Solursh, M., and Gambino, R. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 9303-9307) provide evidence of a genetic heterogeneity of fibrillar collagens in the sea urchin embryo and suggest that the two genes are activated in the same cell lineages at distinct developmental stages. PMID- 2324113 TI - Functional characterization of the 5'-regulatory region of human factor IX gene. AB - Functional characterization of the 5'-regulatory region of the human factor IX gene was carried out by a series of gene dissection analyses. The region extending from -175 to -274 of the 5' end flanking sequence is required for the expression of this gene. Within this region, sequence elements AGCCACT at -238 and TCAAAT at -187 were assigned as the functional CAAT box and TATA box, respectively. The transcription initiation site was found to be at -150 for the factor IX chloramphenicol acetyltransferase chimeric gene. A negative regulatory (silencer) activity was located in the region spanning from 1.4 to 1.7 kilobases upstream of the promoter region. This region contains a short sequence element (ATCCTCTCC) known to have such activity. A strong promoter on the opposite strand was also located about 500 base pairs upstream of the promoter. The expression of factor IX gene was highly liver specific, as assessed by Northern blot analysis. Short sequence elements (TGGACC and CTTTGGACT) homologous to the known liver specific elements were located in the vicinity of the defined promoter region. PMID- 2324114 TI - Purification of eukaryotic RNA polymerase II by immunoaffinity chromatography. Elution of active enzyme with protein stabilizing agents from a polyol-responsive monoclonal antibody. AB - Active eukaryotic RNA polymerase II (RNAP II) was purified by immunoaffinity chromatography, using a monoclonal antibody (mAb) that reacts with the highly conserved heptapeptide repeat of the largest subunit. This mAb (designated SWG16) was conjugated to CNBr-activated Sepharose and used to purify RNAP II from wheat germ and calf thymus. The subunit composition of the immunoaffinity-purified enzyme was essentially the same as RNAP II purified by conventional chromatography except that it contained only the form with the unproteolyzed largest subunit. Active enzyme could be eluted from the SWG16-Sepharose, at pH 7.9, with combinations of low molecular weight polyols and nonchaotropic salts. The superior eluting procedure used combinations of ethylene glycol (30-40%) and ammonium sulfate (0.5-0.75 M). Active enzyme also could be eluted with a synthetic peptide containing four repeats of the heptapeptide; however, the peptide was not as effective as the polyol and salt combinations for eluting the enzyme. This mAb should be useful for purifying RNAP II from many eukaryotic species. Because the elution of enzyme from the immunoadsorbent seems to be dependent upon the presence of a polyol, this antibody is referred to as a "polyol-responsive mAb." A procedure that helps to identify a polyol-responsive mAb and to optimize the eluting conditions is described. Polyol-responsive mAbs might have broad applicability to the purification of many labile enzymes by immunoaffinity chromatography. PMID- 2324115 TI - A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin. AB - Intravascular clot formation, localized to the neoplasm, is an early component of the vascular response to tumor necrosis factor (TNF)/cachectin. Fibrin is closely associated with the endothelial cell surface, and multiple microthromboses lead to reduced blood flow in the tumor. We have identified a tumor-derived mediator which enhances endothelial procoagulant activity and the cellular response to TNF using cultured cells derived from a murine methylcholanthrene A (meth A)-induced fibrosarcoma as a model system. A heat-stable protease K-sensitive polypeptide, Mr approximately 44,000 on nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr approximately 56,000 reduced), was purified approximately 500,000-fold from serum-free culture supernatants of meth A cells by sequential Q Sepharose, Mono S, reversed phase, and preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis. Based on immunologic criteria, biologic activity, and other molecular properties, meth A factor appears to be distinct from other cytokines and growth factors. Purified meth A factor induced transcription of the tissue factor gene and expression of procoagulant activity by cultured human endothelium (half-maximal effect for the latter at approximately 6-8 pM). Furthermore, co-incubation of endothelium with meth A factor together with TNF enhanced induction of tissue factor in a more than additive manner. These data indicate that certain tumors elaborate an apparently unique molecule which can alter hemostatic properties of the vessel wall, potentially modulating reactivity of the tumor vasculature to host response mediators. PMID- 2324116 TI - Purification and biochemical characterization of phenylacetyl-CoA ligase from Pseudomonas putida. A specific enzyme for the catabolism of phenylacetic acid. AB - A new enzyme, phenylacetyl-CoA ligase (AMP-forming) (PA-CoA ligase, EC 6.2.1-) involved in the catabolism of phenylacetic acid (PAA) in Pseudomonas putida is described and characterized. PA-CoA ligase was specifically induced by PAA when P. putida was grown in a chemically defined medium in which phenylacetic acid was the sole carbon source. Hydroxyl, methyl-phenylacetyl derivatives, and other PAA close structural molecules did not induce the synthesis of this enzyme and neither did acetic, butyric, succinic, nor fatty acids (greater than C5 atoms carbon length). PA-CoA ligase requires ATP, CoA, PAA, and MgCl2 for its activity. The maximal rate of catalysis was achieved in 50 mM HCl/Tris buffer, pH 8.2, at 30 degrees C and under these conditions, the Km calculated for ATP, CoA, and PAA were 9.7, 1.0, and 16.5 mM, respectively. The enzyme is inhibited by some divalent cations (Cu2+, Zn2+, and Hg2+) and by the sulfhydryl reagents N ethylmaleimide, 5,5'-dithiobis(2-nitrobenzoic acid), and p-chloromercuribenzoate. PA-CoA ligase was purified to homogeneity (513-fold). It runs as a single polypeptide in 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and has a molecular mass of 48 +/- 1 kDa. PA-CoA ligase does not use as substrate either 3-hydroxyphenylacetic, 4-hydroxyphenylacetic, or 3,4-dihydroxyphenylacetic acids and shows a substrate specificity different from other acyl-CoA-activating enzymes. The enzyme is detected in P. putida from the early logarithmic phase of growth and is repressed by glucose, suggesting that PA-CoA ligase is a specific enzyme involved in the utilization of PAA as energy source. PMID- 2324117 TI - Axial flow velocity patterns in a normal human pulmonary artery model: pulsatile in vitro studies. AB - It has been clinically observed that the flow velocity patterns in the pulmonary artery are directly modified by disease. The present study addresses the hypothesis that altered velocity patterns relate to the severity of various diseases in the pulmonary artery. This paper lays a foundation for that analysis by providing a detailed description of flow velocity patterns in the normal pulmonary artery, using flow visualization and laser Doppler anemometry techniques. The studies were conducted in an in vitro rigid model in a right heart pulse duplicator system. In the main pulmonary artery, a broad central flow field was observed throughout systole. The maximum axial velocity (150 cm s-1) was measured at peak systole. In the left pulmonary artery, the axial velocities were approximately evenly distributed in the perpendicular plane. However, in the bifurcation plane, they were slightly skewed toward the inner wall at peak systole and during the deceleration phase. In the right pulmonary artery, the axial velocity in the perpendicular plane had a very marked M-shaped profile at peak systole and during the deceleration phase, due to a pair of strong secondary flows. In the bifurcation plane, higher axial velocities were observed along the inner wall, while lower axial velocities were observed along the outer wall and in the center. Overall, relatively low levels of turbulence were observed in all the branches during systole. The maximum turbulence intensity measured was at the boundary of the broad central flow field in the main pulmonary artery at peak systole. PMID- 2324118 TI - Modelling human tibia structural vibrations. AB - Mode shapes and natural frequencies of human long bones play an important role in the interpretation, prediction and control of their dynamic response to external mechanical loads. This paper describes an experimental and theoretical study of free vibrations in an excised human tibia. Experimentally, seven tibial natural frequencies in the range 0-3 kHz were identified through measured structural transfer functions. Theoretically, a beam type Finite Element model of a human tibia is suggested. Unknown parameters in this model are determined by a Bayesian parameter estimation approach, by which very fine model/observation-accordance was achieved with realistic parameter estimates. A sensitivity analysis of the model confirms that the human tibia in a vibrational sense is more uniform than its complicated geometry would immediately suggest. Accordingly, two simple tibia models are identified, based on uniform beam theory with inclusion of shear deformations. PMID- 2324119 TI - Techniques used by elite long jumpers in preparation for takeoff. AB - It was hypothesized that some characteristics of the positions adopted by long jumpers during the final strides of the approach are significantly related to the distance of the jump, and that they are so related only by virtue of their relationships with the horizontal velocity at touchdown and/or the vertical velocity at takeoff. Trials by 20 male and 26 female long jumpers were recorded cinematographically and subsequently analyzed. The takeoff distance for the fourth-last stride, the landing distance for the last stride, and the height of the center of gravity (CG) at takeoff into the jump were significantly correlated with the distance of the jump. These three position variables were significantly related to the distance of the jump, through their relationships with the velocity of the approach and the vertical velocity of the CG at takeoff into the jump. Considered alone, they were not influential in determining the distance of the jump. PMID- 2324120 TI - A theoretical study of the influence of bone maturation rate on surface remodeling predictions: idealized models. AB - The use of a finite element based computational method, RFEM3D, is described for the study of strain-induced bone remodeling. The purpose of the research is to find the potential influence on the predictions of surface bone remodeling when various models for the maturation of newly deposited bone are used. A parameter study is performed using seven hypothetical mechanical descriptions of the bone maturation process. The results show that, theoretically, the process of surface bone maturation may be an efficient mechanism for reducing overload strains in bone, but that differences as a consequence of using any of the proposed maturation rules are rather subtle. PMID- 2324121 TI - Measurement errors in roentgen-stereophotogrammetric joint-motion analysis. AB - In many biomechanical motion studies, kinematic parameters are estimated from position measurements on a number of landmarks. In the present investigation, dummy motion experiments are performed in order to study the error dependence of kinematic parameters on geometric factors (number of markers, isotropic vs anisotropic landmark distributions, landmark distribution size), on kinematic factors (rotation step magnitude, the presence of translational displacements, the distance of the landmarks' mean position to the rotation axis), and on anisotropically distributed measurement errors. The experimental results are compared with theoretical predictions of a previous error analysis assuming isotropic conditions for the measurement errors and for the spatial landmark distribution. In general, the experimental findings agree with the predictions of the error model. The kinematic parameters such as translations and rotations are well-determined by the model. In the helical motion description, the same applies for the finite rotation angle about and the finite shift along the helical axis. However, the direction and position of the helical axis are ill-determined. An anisotropic landmark distribution with relatively few markers located in the direction of the rotation axis will even aggravate the ill-posed nature of the finite helical axis estimation. PMID- 2324122 TI - A model of semitendinosus muscle sarcomere length, knee and hip joint interaction in the frog hindlimb. AB - The interaction between the semitendinosus muscle and both hip and knee joint angles was examined in the frog (Rana pipiens) hindlimb. Sarcomere length was measured by laser diffraction in passive muscle during hip and knee rotation. A model was then developed to predict semitendinosus sarcomere length as a function of both hip and knee flexion angle. Based on published frog muscle fiber length tension [Gordon, A. M. et al., J. Physiol. 184, 170-192 (1966)] and force velocity [Edman, K. A. P., J. Physiol. 291, 143-159 (1979)] properties, and published joint angles during hopping [Calow, L. J. and Alexander, R. McN., J. Zool. (Lond.) 171, 293-321 (1973)], muscle sarcomere length, force and hip and knee torque during a hop were predicted. The semitendinosus muscle generally operated on the descending limb of the length-tension curve at normal joint angle combinations. The model predicted that, during a single coordinated movement, a period of sarcomere shortening (concentric) was followed by a period of sarcomere lengthening (eccentric). Based on calculated torque profiles at the hip and knee joints, this study suggested that the semitendinosus muscle probably functions more as a hip extensor than a knee flexor. In addition, based on the nature of the shortening-lengthening cycle, the semitendinosus may act to mechanically link the force of knee extension to hip extension. PMID- 2324123 TI - Mechanical and failure behaviour of the stratum corneum. AB - The load-deformation-time behaviour of heat-separated human stratum corneum was investigated using a pure shear specimen geometry. The tissue displayed non linear load-deformation behaviour and stress relaxation, although the extensibility and amount of stress relaxation was considerably less than that shown by other soft connective tissues. Controlled failure tests were carried out after an edge cut had been made in the pure shear specimen. Sources of secondary failure, either at the free edge of the specimen, or due to the presence of inhomogeneities in the tissues, were common. Analysis of the test results suggested that the fracture surface energy of stratum corneum has a mean value of 3.6 kJ m-2 which is comparable with the tougher synthetic polymers. PMID- 2324124 TI - Effect of testing mode on the biomechanical response of a spinal motion segment. PMID- 2324125 TI - Enzymatic activity toward poly(L-lactic acid) implants. AB - Tissue reactions toward biodegradable poly(L-lactic acid) implants were monitored by studying the activity pattern of seven enzymes as a function of time: alkaline phosphatase, acid phosphatase, alpha-naphthylacetyl esterase, beta-glucuronidase, ATP-ase, NADH-reductase, and lactate dehydrogenase. Cell types were identified by their specific enzyme patterns, their morphology and location. Special attention was paid to the enzyme patterns of macrophages, fibroblasts and polymorphonuclear granulocytes (PMNs), being involved in foreign body reactions or inflammatory responses. One day after implantation, an influx of neutrophilic and eosinophilic granulocytes was observed, coinciding with activity of alkaline phosphatase (PMN's) and beta-glucuronidase (eosinophils). From day 3 on, macrophages containing ATP-ase, acid phosphatase and esterase could be observed. From day 7 on, lactate dehydrogenase, the enzyme normally involved in the conversion of lactic acid, and its coenzyme NADH-reductase were observed in macrophages and fibroblasts. These two enzymes demonstrated more activity than expected on basis of wound-healing reactions upon implantation of a nonbiodegradable, inert biomaterial (as, e.g., Teflon). It is concluded that the biodegradable poly (L lactic acid) used in these implantation studies is tissue compatible, and evokes a foreign body reaction with minor macrophage and giant cell activity, as observed during this 3-week implantation period. Most enzyme patterns were simply due to a wound-healing reaction. The slightly increased levels of LDH and NADH suggest the release of lactic acid from the implant, and thus confirms the biodegradable nature of this polymer. PMID- 2324126 TI - Poly(dimethylsiloxane)-poly(ethylene oxide)-heparin block copolymers. III: Surface and bulk compositional differences. AB - Previously observed bioactivity of poly(dimethylsiloxane)-poly(ethylene oxide) heparin (PDMS-PEO-Hep) triblock copolymers has prompted studies of the surface and bulk character of this copolymer using angular-dependent electron spectroscopy for chemical analysis (ADESCA), static secondary mass spectroscopy (SIMS), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Because the low-energy PDMS phase dominates surfaces of this copolymer when solvent cast under air or vacuum conditions, attempts were made to explain surface restructuring and rearrangements induced in hydrated or aqueous environments that permit surface accessibility and bioactivity of heparin moieties. Based on comparisons with PDMS, PEO, and heparin homopolymers, PEO/heparin blends, and an unheparinized PDMS-PEO diblock copolymer, PDMS-PEO heparin demonstrates both phase-mixed and phase-separated regions in DSC analysis. During annealing cycles above the Tg values of the copolymer constituents, phase-mixed regions become increasingly phase separated and PEO enriched. TGA analysis confirmed the presence block copolymer constituents and presented evidence of intermolecular segmental interactions, hence phase-mixing in the copolymers. ADESCA analysis indicates that the outer 5 A of both the PDMS PEO and PDMS-PEO-Hep copolymers is essentially pure PDMS. However, significant amounts of PEO are detected 5 to 20 A below the surface. Static SIMS also detects the presence of PDMS at the surfaces of the PDMS-PEO and PDMS-PEO-Hep copolymers. Compositional models based on ADESCA, SIMS, and DSC data are presented for desiccated and hydrated copolymer surfaces. PMID- 2324127 TI - Effect of vacuum mixing on the mechanical properties of antibiotic-impregnated polymethylmethacrylate bone cement. AB - Polymethylmethacrylate bone cement, containing either no added antibiotic, 0.5 g of Vancomycin, 1.0 g of Vancomycin, or 1.0 g of Tobramycin, was mixed either in air or a vacuum chamber. Following storage in a water bath at 37 degrees C for 48 h, the specimens were tested in four-point bending. The porosity of the specimens was assessed radiographically, and their antibacterial activity was monitored for 21 days. The bending strength of the vacuum mixed specimens containing no antibiotic was 40% greater than that of similar air-mixed specimens. However, there were no significant differences in the bending strength of either the air- or vacuum-mixed specimens when any of the antibiotic dosages were added. The bending modulus of the vacuum-mixed specimens, containing no antibiotic, was significantly greater than the moduli of all the other specimen groups which did not differ from each other. Vacuum mixing reduced the apparent porosity of the specimens fivefold, and while the addition of antibiotic did not effect porosity of the air-mixed specimens, that of the vacuum-mixed specimens was doubled. Although initial rapid decreases were seen, leaching of antibiotic from the cement and antibacterial activity continued through the 21-day monitoring period. PMID- 2324128 TI - The effect of gamma-irradiation on collagen molecules, isolated alpha-chains, and crosslinked native fibers. AB - This study shows how collagen molecules are readily damaged by gamma-radiation at dosages commonly used for sterilizing biomedical products. At 1 Mrad, while the reported effectiveness of the radiation at such a low dosage to completely sterilize a material is questionable, less damage was caused to the collagen peptide backbone. Above such dosage, however, significant damage was clearly demonstrated with collagen alone and collagen in a chemically crosslinked tissue matrix. The enzyme digestion study showed that the material exposed to a very high dosage of radiation resisted degradation by pronase. However, molecular weight analysis showed a significant number of peptide bonds being cleaved by the radiation which could cause considerable changes in the long-term characteristics of the material. Therefore, tissues exposed to high dosages of gamma-radiation should be tested for long term functional changes. We want to caution against the usage of the enzyme degradation assay as a universal test for all bioprosthetic derived from biological tissues. PMID- 2324129 TI - Stress enhancement and fatigue susceptibility of porous coated Ti-6Al-4V implants: an elastic analysis. AB - An elastic stress analysis of porous-coated implant surfaces was performed using the finite element method. Three-hundred-microns-diameter metal beads sinter bonded onto an implant surface were modeled with sinter neck radii of 5, 10, 20, and 50 microns. Smooth-surface, single-bead, single-layer, and double-layer systems were analyzed. The finite element models were loaded to simulate bone bead contact forces and lateral hip implant tensile forces. Results showed that, for a single bead sinter-bonded onto an implant surface, concentration of stress occurs either at the base of the sinter neck or within the neck itself, depending on the type of load applied. Under lateral hip implant tensile loads, a maximum stress concentration factor of 1.97 was obtained for a single bead sinter-bonded onto a implant surface. Addition of a single layer of beads onto the implant surface resulted in a significant increase in stress at the most proximal and distal ends of the porous layer, with a maximum stress concentration factor of 4.3. Addition of a second layer of beads did not significantly increase the magnitude of the stress concentration occurring at the ends of the porous layer. The results of this study provide stress concentration factors for porous coatings with sinter necks of known dimensions under loading conditions similar to those present along the lateral surface of a hip prosthesis. PMID- 2324130 TI - Characterization of alkyl grafted polyurethane block copolymers by variable takeoff angle x-ray photoelectron spectroscopy. AB - Variable takeoff angle x-ray photoelectron spectroscopy was used to determine the surface composition of five polyurethane block copolymers. The high-resolution C1s spectra from all five polyurethane samples had peaks at binding energies of 285.0, 286.5, and 289.5 eV, which are consistent with the presence of hydrocarbon, ether, and urethane carbon species. Both the measured elemental compositions at the low takeoff angles (deepest sampling depths) and the calculated elemental compositions for depths greater than 15 A generally showed good agreement with the expected bulk compositions. The outer 15 A of the surface of all five samples was depleted in the nitrogen-containing hard segment. For the base polyurethane sample in this series, an enrichment of the poly(tetramethylene oxide) soft segment and the presence of an organic silicone impurity were detected. Doubling the chain length of both the hard and soft segments resulted in a further decrease of the hard segment concentration in the outer surface of the sample. The grafting of C2 and C18 alkyl groups onto 10 or 20% of the urethane linkages resulted in an increase in the percentage of aliphatic carbon species present on the surface. In the case of the C18-alkylated material, the presence of alkyl chains at the surface was inferred using contact angle measurements. PMID- 2324132 TI - Opportunities, responsibilities. PMID- 2324131 TI - Cellular interactions with biomaterials: in vivo cracking of pre-stressed Pellethane 2363-80A. AB - The phenomenon of stress cracking of Pellethane 2363-80A (PEU) was investigated using the cage implant system. A cytotoxic polyvinylchloride (PVC) and a silicone rubber containing an anti-inflammatory steroid were used to create inflammatory environments in which the biostability of the pre-stressed PEU was tested. These coimplants provided alternative in vivo environments to study in vivo polymer interactions. The inflammatory responses to the implanted cages were monitored by analyzing the exudates aspirated from the cages at different implantation times over 21 days. The pre-stressed PEU specimens were retrieved after 5, 10, and 15 weeks postimplantation and examined by optical microscopy (OM) and scanning electron microscopy (SEM). The results support the conclusion that in vivo cracking of stressed (strained) Pellethane 80A is related to cell-polymer interactions. Severe cracking or rupture of the implanted PEU specimens was observed as early as 5 weeks postimplantation. Molecular chain degradation of the implanted specimens was evident from molecular weight measurements. Neither surface cracking nor degradation of macromolecules was found on the pre-stressed PEU specimens with the added cytotoxic PVC implanted over 15 weeks. No cracking was observed on the pre-stressed specimens in the presence of steroid silicone rubber, even after 10 weeks implantation. PMID- 2324133 TI - Winds of change. PMID- 2324134 TI - Dual-fibular grafting for massive bone gaps in the lower extremity. AB - Fifty-two patients who had a tumor in the lower extremity (thirty-seven, a giant cell tumor and fifteen, a small osteosarcoma that had not metastasized) had dual fibular strut-grafting to bridge the osseous gap resulting from excision of the tumor. The size of the gap ranged from nine to twenty-four centimeters. The average time until union ranged from ten to twenty months. The ipsilateral fibula was used in thirty-six patients and both fibulae, in the remaining sixteen patients. Immediate reimplantation and adequate fixation of the fibular graft to the proximal and distal ends of the bone to be grafted, along with placement of a cuff of cancellous bone at the host-graft junction and between the fibular struts, fostered early union of the graft to the host bone. Insertion of Kirschner wires inside these long grafts helped to maintain continuity of the graft when a stress fracture occurred. Eight patients who had a non-union at one of the host-graft sites and three who had a stress fracture had subsequent cancellous bone-grafting to obtain union. Superficial infection was the most common complication and was seen in seventeen patients. PMID- 2324135 TI - Acetabular anatomy and the transacetabular fixation of screws in total hip arthroplasty. AB - An anatomical and radiographic study was undertaken to determine the safest zones in the acetabulum for the transacetabular placement of screws during uncemented acetabular arthroplasty. To avoid injury to intrapelvic structures, which are not visible to the surgeon during placement of the screws, cadavera were studied to define the location of these structures with respect to fixed points of reference within the acetabulum. Four clinically useful acetabular quadrants were delineated. The quadrants are formed by drawing a line from the anterior superior iliac spine through the center of the acetabulum to the posterior fovea, forming acetabular halves. A second line is then drawn perpendicular to the first at the mid-point of the acetabulum, forming four quadrants. The posterior superior and posterior inferior acetabular quadrants contain the best available bone stock and are relatively safe for the transacetabular placement of screws. The anterior superior and anterior inferior quandrants should be avoided whenever possible, because screws placed improperly in these quadrants may endanger the external iliac artery and vein, as well as the obturator nerve, artery, and vein. The acetabular-quadrant system provides the surgeon with a simple intraoperative guide to the safe transacetabular placement of screws during primary and revision acetabular arthroplasty. PMID- 2324136 TI - Structures at risk from medially placed acetabular screws. AB - The anatomical structures adjacent to fourteen acetabula were studied to identify structures that are at risk from acetabular screws. There were six embalmed acetabula, four acetabula from two fresh autopsy specimens, and four acetabula that were studied during two gynecological operations. Models were constructed to show where these screws can penetrate. Medially placed screws either penetrated or came dangerously close to the external iliac vein; the obturator artery, nerve, and vein; and tributaries of the internal iliac vein. To avoid injury to the medial vascular structures, screws should not be placed in the anterosuperior quadrant of the acetabulum. PMID- 2324137 TI - In vivo wear of titanium-alloy hip prostheses. AB - We examined samples of tissue and components that had been removed during twenty revisions of total hip arthroplasties in which a titanium-alloy femoral component had been used. Minute amounts of metallic debris were detected in the tissues from two patients. The amounts of polyethylene and methylmethacrylate debris and the histological reactions in the tissues corresponded closely with those reported in earlier studies of total hip prostheses made of stainless steel or cobalt-chromium alloy. PMID- 2324138 TI - Effect of femoral head size on wear of the polyethylene acetabular component. AB - A technique was developed to determine the wear of the acetabular component of a total hip replacement by examination of standardized initial and follow-up radiographs. Three hundred and eighty-five hips were followed for at least 9.5 years after replacement. The least amount and rate of linear wear were associated with use of a femoral head that had a diameter of twenty-eight millimeters (p less than 0.001). The greatest amount and mean rate of linear wear occurred with twenty-two-millimeter components, but these differences were not statistically significant. The greatest volumetric wear and mean rate rate of volumetric wear were seen with thirty-two-millimeter components (p less than 0.001). A wider radiolucent line in acetabular Zone 1 was associated with use of the thirty-two millimeter head. The amounts of resorption of the proximal part of the femoral neck and of lysis of the proximal part of the femur both correlated positively with the extent of linear and volumetric wear; this suggests an association between the amount of debris from wear and these changes in the femoral neck and proximal part of the femur. PMID- 2324139 TI - Total condylar knee replacement in patients who have rheumatoid arthritis. A ten year follow-up study. AB - Eighty knee replacements with a total condylar prosthesis in patients who had rheumatoid arthritis were followed for ten years. At ten years, nineteen knees needed revision and sixty-one prostheses were still functioning. The major reasons for revision were loosening of the tibial component or late bacteremic seeding from another site. Radiolucency at the bone-cement interface adjacent to the tibial component was statistically related to malposition of the tibial component. According to the system of The Hospital for Special Surgery, the mean scores were 64 points preoperatively and 85 points postoperatively. Synovitis recurred in only 3 per cent of the knees. When revision, pain, or radiographic evidence of loosening were considered an indication of failure, the ten-year cumulative survival was 75 per cent. PMID- 2324140 TI - One-stage anterior and posterior hemivertebral resection and arthrodesis for congenital scoliosis. AB - Seven children who had congenital scoliosis due to a single, fully segmented lumbar hemivertebra were treated with single-stage anterior and posterior vertebral resection and arthrodesis. The scoliosis averaged 47 degrees preoperatively, 14 degrees postoperatively, and 15 degrees (approximately 70 per cent correction) after an average follow-up of 45.6 months. Four patients had thoracolumbar kyphosis preoperatively, and it remained unchanged at the most recent follow-up examination. Postoperatively, a cast was worn for twelve to sixteen weeks, after which a brace was applied. There were no neurological deficits, infections, deaths, or pseudarthroses. The combined procedure was well tolerated and, in the limited period of follow-up, the congenital scoliosis did not progress. PMID- 2324141 TI - Symptoms and level of sports activity in patients awaiting arthroscopy for meniscal lesions of the knee. AB - Thirty-six patients who had symptoms suggestive of lesions of the meniscus of the knee were put on a waiting list for arthroscopy. Patients who had a locked knee, had had more than two episodes of locking, or had unrelieved swelling were given preference on the waiting list and were not included in the study. By the time of admission to the hospital for elective arthroscopy, six to twenty-four months after being placed on the waiting list, none of the thirty-six patients had worse symptoms: four had no change in symptoms (although two of these had stopped or reduced their sports activity), nine had no symptoms (but six of these no longer participated in sports), and the remaining twenty-three had partial relief of symptoms (but seventeen of the twenty-three no longer participated in sports or had reduced their activity). Four patients remained unable to work. Only two of the twenty-seven who had engaged in sports before they had symptoms resumed their normal sports activity. By the time of admission to the hospital, fourteen patients had decided not to go ahead with the arthroscopy; eight of these had decided to give up sports indefinitely. Of the twenty-two patients who had an arthroscopy, a meniscal abnormality was found in twelve. In two of these, a healed meniscal lesion was found. PMID- 2324142 TI - Arthrodesis of the ankle with modified distraction-compression and bone-grafting. AB - A modification of the technique of Chuinard and Peterson for distraction compression arthrodesis of the ankle was used in twelve patients, whose ages ranged from ten to seventy-one years. This modified technique allows positioning that is better for function and it makes fusion more certain. It also offers the advantages of the original technique--that is, it preserves the potential for growth of the distal tibial and fibular physes and it maintains the height of the malleolus and foot. The duration of follow-up averaged four years and three months. The preoperative diagnoses were degenerative arthritis, poliomyelitis, talipes equinovarus, and myelodysplasia. Solid fusion was achieved in all patients, although one patient needed reoperation before fusion was achieved. The time to fusion averaged eleven months (range, three to sixteen months). The functional result was good in all patients. PMID- 2324143 TI - Direct measurement of resultant forces in the anterior cruciate ligament. An in vitro study performed with a new experimental technique. AB - A new technique was used to measure the resultant forces in the anterior cruciate ligament during a series of loading experiments on seventeen fresh-frozen cadaver specimens. The base of the ligament's tibial attachment was mechanically isolated with a coring cutter, and a specially designed load-transducer was fixed to the bone-plug that contained the ligament's tibial insertion so that the resultant forces were directly measured by the load-cell. Although the magnitudes of values for forces varied considerably between specimens for a given test condition, the patterns of loading with respect to direction of loading and the angle of flexion of the knee were remarkably consistent. Passive extension of the knee generated forces in the ligament only during the last 10 degrees of extension; at 5 degrees of hyperextension, the forces ranged from fifty to 240 newtons (mean, 118 newtons). When a 200-newton pull of the quadriceps tendon was applied to extend a knee slowly against tibial resistance, however, the force in the ligament increased at all angles of flexion of the knee. Internal tibial torque always generated greater forces in the ligament than did external tibial torque; higher forces were recorded as the knee was extended. The greatest forces (133 to 370 newtons) were generated when ten newton-meters of internal tibial torque was applied to a hyperextended knee. Fifteen newton-meters of applied varus moment generated forces of ninety-four to 177 newtons at full extension; fifteen newton meters of applied valgus moment generated a mean force of fifty-six newtons, which remained unchanged with flexion of the knee. The force during straight anterior translation of the tibia was approximately equal to the anterior force applied to the tibia. The application of 925 newtons of tibiofemoral contact force reduced the mean force in the ligament that was generated by 200 newtons of anterior pull on the tibia by 36 per cent at full extension and 46 per cent at 20 degrees of flexion. PMID- 2324144 TI - Pathological fractures in patients who have amyloidosis associated with dialysis. A report of five cases. AB - We are reporting the cases of five patients in whom a pathological fracture of the femoral neck developed secondary to massive deposition of amyloid while they were receiving maintenance hemodialysis. The immunohistochemical studies demonstrated the presence of beta-2-microglobulin as the major constituent protein of the amyloid deposits. PMID- 2324146 TI - Arthrodesis of the shoulder in children. AB - Ten children had an arthrodesis of the shoulder for a paralytic condition involving the muscles; nine of them were available for long-term follow-up. In the children who were eight to fifteen years old at the time of operation, the angle of arthrodesis was 45 degrees of abduction, 25 degrees of flexion, and 25 degrees of internal rotation. This angle allowed symptomless and useful function of the extremity. No patient had a stress fracture or discomfort when the arm was at rest at follow-up. An asymptomatic click in the acromioclavicular joint in one patient indicated that this may be a future site of abnormality. The children apparently accommodated easily to the arthrodesis of the shoulder. Neither self image nor overall function seemed to be impaired by the operation. The over-all function postoperatively was related to the neurological integrity of the distal muscles. PMID- 2324145 TI - The viability of articular cartilage in fresh osteochondral allografts after clinical transplantation. AB - The articular cartilage of four fresh osteochondral allografts was biopsied after transplantation, and its viability was studied by autoradiography. The biopsy specimens were labeled with both 3H-cytidine, for newly synthesized ribonucleic acid, and 35S-sulphate, for newly synthesized proteoglycans. The cartilage of a lateral humeral condylar graft at twelve months had 96 to 99 per cent labeled chondrocytes, the articular cartilage of a medial femoral condylar graft at twenty-four months showed 69 to 78 per cent labeled chondrocytes, and the cartilage of a medial tibial-plateau graft at forty-one months had 90 per cent labeled cells. At six years, a lateral tibial-plateau graft had 37 per cent labeled chondrocytes. PMID- 2324147 TI - Treatment of slipped capital femoral epiphysis. Spica-cast immobilization. AB - Thirty-two patients (thirty-seven hips) who had a so-called acute-on-chronic or chronic slipped capital femoral epiphysis were treated with traction for relief of symptoms and then with immobilization in a spica cast for eight to sixteen weeks. The disappearance on radiographs of a metaphyseal juxtaphyseal radiolucency, rather than closure of the physis, was used as the criterion for removing the cast. In one (3 per cent) of the thirty-seven hips, the slip progressed; possibly this could have been prevented by keeping the cast on for a longer period of time. Narrowing of the cartilage space was seen after treatment in a cast in seven (19 per cent) of the thirty-seven hips. In five of these seven hips, this was true chondrolysis; in one, the diagnosis of chondrolysis had been apparent before treatment. Avascular necrosis did not develop as a result of treatment in any patient. Treatment in a spica cast should be considered as an alternative for patients who have an acute-on-chronic or chronic slipped capital femoral epiphysis. PMID- 2324148 TI - Post-traumatic contracture of the elbow. Operative treatment, including distraction arthroplasty. AB - Twenty-six consecutive patients who had post-traumatic contracture of the elbow were treated by operative release alone or by release and distraction arthroplasty, with or without fascial interposition. The type of operative procedure was determined by whether the factors limiting motion were purely extra articular (extrinsic) or whether they included intra-articular (intrinsic) elements as well. The mean preoperative arc of total motion was 30 degrees (from 63 to 93 degrees of flexion). At follow-up examination, twenty-two to ninety-four months post-operatively, of twenty-five patients, the mean arc of total motion was 96 degrees (from 30 to 126 degrees). There were eight complications in seven (27 per cent) of the patients. Of these, four (avulsion of the triceps tendon, deep infection, and two ulnar-nerve paresthesias) were managed by subsequent operative treatment. The other four complications included drainage from a pin site, which resolved after removal of the pin: a three by two-centimeter skin slough, which spontaneously epithelialized; aseptic resorption of the distal end of the humerus and proximal end of the ulna, which stopped after immobilization and subsequent bracing of the elbow but resulted in moderate instability; and ulnar-nerve paresthesia, which was not operatively treated and persisted. Twenty four (96 per cent) of the twenty-five patients who were followed for twenty-two months or more were satisfied with the results of the procedure because of the improved facility in carrying out activities of daily living. No patient had increased pain, but two had moderate instability. It was concluded that the results of distraction arthroplasty can be gratifying, but the technique is demanding and the rate of complications is high. PMID- 2324149 TI - Disassembly of a modular femoral component during closed reduction of the dislocated femoral component. A case report. PMID- 2324150 TI - Disassembly of a modular acetabular component of a total hip-replacement arthroplasty. A case report. PMID- 2324151 TI - Disassembly of a modular femoral prosthesis after dislocation of the femoral component. A case report. PMID- 2324152 TI - Orthopaedic aspects of myelomeningocele. PMID- 2324153 TI - Current concepts review. Slipped capital femoral epiphysis. PMID- 2324154 TI - Avulsion fracture of the lateral acetabular margin. A case report. PMID- 2324155 TI - Sequential high-dose methotrexate, 5-fluorouracil, and doxorubicin for treatment of advanced pancreatic cancer. AB - A phase II trial of sequential high-dose methotrexate, 1500 mg/m2, and 5 fluorouracil, 1500 mg/m2 intravenously on day 1, plus doxorubicin, 30 mg/m2 i.v. on day 14, has been undertaken in patients with locally advanced or metastatic adenocarcinoma of the pancreas. Of 25 evaluable patients there were 1 complete response and 3 partial responses for an overall response rate of 16% (95% confidence interval 5%-36%). The median survival of all patients was 6.7 months (range 1-17 months). There was one treatment-related death due to pancytopenia and sepsis. In all other patients therapy was generally well-tolerated. We conclude that this combination protocol has only modest activity in the treatment of advanced pancreatic cancer. PMID- 2324156 TI - Antitumor effects of a new interleukin-2 slow delivery system on methylcholanthrene-induced fibrosarcoma in mice. AB - The interleukin-2 (IL-2) mini-pellet, the carrier material of which is a biocompatible and biodegradable atelocollagen refined from bovine skin, contains 1 x 10(6) units of IL-2 and can release IL-2 slowly in vivo by diffusion and dissolution. We have evaluated the antitumor effects of the IL-2 mini-pellet on an established solid murine tumor, methylcholanthrene-induced fibrosarcoma (Meth A). The subcutaneous administration of the IL-2 mini-pellet alone on days 8 and 11 after tumor inoculation significantly inhibited tumor growth. A significant inhibition was also seen when it was combined with the intravenous injection of 5 x 10(7) lymphokine-activated killer (LAK) cells, in comparison to the untreated controls. Moreover, therapy with the IL-2 mini-pellet alone or in combination with LAK cells also prolonged the survival of mice bearing Meth A fibrosarcoma. In order to determine the precise mechanism of action of these antitumor effects, we tested splenocytes of treated mice for cytotoxic activity in vitro and investigated tumor tissues by an immunohistochemical method. On day 2 after the administration of the IL-2 mini-pellet, the lytic activity of splenocytes against both YAC-1 and JTC-11 cells (i.e. NK and LAK activity) was significantly augmented, and on day 7 a massive accumulation of lymphocytes, which were mainly like Thy1+ and/or asialo-GM1+ LAK cells, was seen in the tumor. These findings indicate that the IL-2 mini-pellet is an appropriate system for local administration of IL-2 and can induce LAK-like effector cells at the target site. PMID- 2324158 TI - DNA repair systems in early and persistent hepatocyte nodules in the rat. AB - The repair of three DNA lesions, namely O6-methylguanine, 7-methylguanine, and 3 methyladenine, was investigated within early and persistent hepatocyte nodules generated in Fischer 344 rats by a modified Solt-Farber procedure (diethylnitrosamine initiation followed by a 2-acetylaminofluorene/CCl4 cycle). The O6-methylguanine-DNA methyltransferase concentration within both hepatocyte nodule types was always higher than that found in age-matched controls (normal, initiated-only and promoted-only livers). As far as 3-methyladenine and 7 methylguanine-DNA glycosylases are concerned, the early hepatocyte nodules showed far higher activities for both enzymes than were found in the controls, whereas in the persistent ones they underwent a significant decrease. In conclusion hepatocyte nodules are endowed with a high DNA repair activity, which is partly adaptive, partly constitutive; along with others, such a defence mechanism could allow transformed cells to resist many cytotoxic drugs. PMID- 2324157 TI - Long-term persistence of DNA alkylation in hamster tissues after N-nitrosobis(2 oxopropyl)amine. AB - The persistence of 7- and O6-alkylation of guanine in DNA of cell nuclei of male Syrian hamster pancreas, liver, kidneys, lungs [target tissues of N-nitrosobis(2 oxopropyl)amine (BOP)] and salivary glands (nontarget tissue) was studied immunocytochemically 6 h, 1, 3, 7, 14, 28, and 56 days after a single s.c. injection of 20 mg BOP/kg. Conventional antisera raised against O6-methylguanine and imidazole-ring-opened 7-methyl-guanine were used. Persistent alkyl-specific staining was observed for up to 7 days (7-alkylguanine) or 56 days (O6 alkylguanine) in inter- and intralobular duct cells and centro-acinar cells of the pancreas, periportal hepatocytes and bile duct cells of the liver, cells of the proximal convoluted tubules of the renal cortex, and bronchiolar Clara and alveolar cells in the lungs. Both adducts disappeared from centrilobular liver cells within 1 day, from pancreatic acinar cells within 3 days, and from ducts and acini of the submandibular salivary glands within 14 days after BOP treatment. A high level of persistent O6-alkylation of guanine was related with a high tumor incidence only in case of the ductal/ductular system of the pancreas, the main target tissue of BOP-induced carcinogenesis. The relatively weak carcinogenicity of BOP in other tissues with long-term persistence of O6 alkylguanine in DNA indicates that the formation and persistence of DNA alkylation are not sufficient to account for the carcinogenic organotropism of BOP. Additional factors, such as cell proliferation, appropriate promoting stimuli and the (onco)genes critically involved, may be as important as the modification of DNA. PMID- 2324159 TI - The tumor-inhibiting effect of diethylstilbestrol and its diphosphate on the Nb-H and Nb-R prostatic carcinomas of the rat. AB - For many years, diethylstilbestrol (DES) and its diphosphate (DESPP; Honvan) have been standard therapies for prostatic carcinoma. The effects of DES, its monophosphate (DESP) and of DESPP on the weights of accessory sex organs of mice and rats, and on the experimental Noble Nb-H and Nb-R prostatic carcinomas of the rat were, therefore, compared. In intact mature mice, all three compounds led to a strong and dose-dependent inhibition of seminal vesicle weights and testosterone levels, whereas only a slight antiandrogenic activity in castrated mice was found. In intact rats, DES, DESP and DESPP strongly inhibited accessory sex organ weights and testosterone levels. In castrated rats, however, no antiandrogenic activity was determinable. The prostate carcinoma-inhibiting effects of DES and DESPP were tested in comparison with castration in the transplantable hormone-sensitive Nb-H and Nb-R prostatic carcinoma in rats. Whereas castration caused only a retardation of tumor growth, DES and DESPP (3 x 0.1 mg/kg and 1.0 mg/kg weekly s.c.) led to an almost complete inhibition, which was significantly (P less than 0.01) better than the effect of castration. As the weights of accessory sex organs were identically reduced by either castration or the estrogens, a direct tumor-inhibiting effect of DES and DESPP in addition to their testosterone-lowering activity is obvious. This was proved in an experiment with castrated rats. The only slightly inhibitory activity of castration was strongly potentiated by concomitant administration of DES. Moreover, histological examinations revealed that Nb-H and Nb-R tumors were much more damaged by treatment with DES or DESPP than after castration. Morphometry of the tumors showed that tumor reduction is associated with a decrease in the ratio of the epithelial to the stromal density, i.e. there was an even more pronounced decrease in epithelial cells than that found by merely measuring tumor area. These studies show that the prostate carcinoma-inhibiting effect of DES and DESPP in the Nb model is superior to the effect of castration and that they act directly on the tumor cells used, even in castrated rats. PMID- 2324160 TI - Antimetastatic effect of defibrinogenation with batroxobin depends on the natural killer activity of host in mice. AB - Using batroxobin, a thrombin-like enzyme found in snake venom, the effects of defibrinogenation on artificial lung metastasis in mice were studied. The role of natural killer (NK) cells in the inhibitory effects of defibrinogenation on metastasis was also investigated. Artificial lung metastasis experiments were performed by inoculating either B16-F10 cells or B16-BL/6 cells, highly metastatic strains of B16 melanoma cells, into C57BL/6 mice via the tail vein. The administration of batroxobin significantly inhibited lung metastasis, as did NK activity augmented by poly (I).poly (C) were administered, lung metastasis was more markedly inhibited. When NK activity was suppressed by administration of anti-(asialo GM1) antibody, lung metastasis was markedly increased. When batroxobin was administered with anti-(asialo GM1) antibody, no inhibitory effects on lung metastasis, such as those seen with batroxobin alone, were observed. The administration of batroxobin had no effect at all on spleen lymphocyte NK activity. These results indicated that defibrinogenation due to batroxobin inhibits lung metastasis, and these effects depend on NK activity of the host. PMID- 2324162 TI - Ethanol vapour modulation of Lewis lung carcinoma, a murine pulmonary tumour. AB - Pure ethanol in experimental animal studies, may not primarily be carcinogenic, but secondarily it can act chemically and synergistically as a co-carcinogen via its endogenous metabolites and associated dietary and exogenous factors. However, ethanol, being a small molecule and miscible with water and most lipids, can readily enter cell membranes and directly affect cell function. In an in vitro study where ethanol was added to the culture medium for Lewis lung carcinoma, a dose-dependent suppression of tumour growth occurred. In the in vivo study, sequestration of the Lewis lung carcinoma in the lungs followed tail-vein injection in C57BL/6 mice. Starting on the second day after tumour implantation, primary pulmonary exposure was carried out with inhalations of 0.4% ethanol vapour from an aerosol for 70 min daily, this was continued for 17 days. This resulted in a marked reduction of the pulmonary tumour growth. Exposure to 0.1% ethanol vapour did not significantly affect the growth of Lewis lung carcinoma tumour. The optimum ethanol aerosol applications may thus be tumoricidal. Whether any ethanol secondary metabolites are involved is as yet uncertain. PMID- 2324161 TI - Responses of a murine B16 melanoma to pharmacotherapy studied and compared with different assay systems. AB - The responses of B16 melanoma in C57BL mice to cytotoxic agents, cyclophosphamide, doxorubicin, and dactinomycin, were studied by different methods both in vivo and in vitro. Either treated tumors were allowed to grow in vivo or cells were isolated and cultured in vitro afterwards. The tumor cells were also treated in vitro and assayed in vitro. For cyclophosphamide, a fairly good correlation was found among the dose responses measured: the tumor growth delay, incidence of giant cells, decrease in mitotic index, clonogenic cell survival of tumor cells treated in vivo and the survival of cells treated in vitro. For doxorubicin and dactinomycin, on the other hand, the tumor growth delay was not marked, the appearance of giant cells and decrease in mitotic index were minimal, and almost no decrease was found in the clonogenic cell survival for tumor treated in vivo, although the cells responded well to in vitro exposure. The results indicate substantial differences in the expression of damage according to the conditions of tumor cell growth and assay after treatment with different agents. PMID- 2324163 TI - Primary gastrointestinal lymphoma in childhood (up to 18 years of age). A morphological, immunohistochemical and clinical study. AB - A group of 47 patients up to 18 years of age, with primary non-Hodgkin's lymphoma of the gastrointestinal tract, were investigated. The lesions were located in the stomach (n = 2), small intestine (n = 17), the ileocecal region (n = 20), the large intestine (n = 7), and multifocally in the small and large intestines (n = 1). Of the patients, 41 were male and 6 were female; their age at presentation ranged from 2 to 18 years. All of the cases belonged to the high-grade malignancy group of the updated Kiel classification. Burkitt's lymphoma was the most frequent histological type (n = 35), followed by centroblastic lymphoma (n = 3), immunoblastic lymphoma (n = 2), lymphoblastic lymphoma (n = 1), and large-cell anaplastic lymphoma (n = 1). Five of the patients had high-grade unclassified B cell lymphoma. Of all the lymphoma types 41 cases (87%) were positive for Ki-B3 (a B-cell marker). Expression of monoclonal immunoglobulin was demonstrated in 8 of 35 cases (23%) of Burkitt's lymphoma, in all 3 cases of centroblastic lymphoma, in both cases of immunoblastic lymphoma, in the single case of lymphoblastic lymphoma, and in all 5 cases of high-grade unclassified B-cell non Hodgkins lymphoma. Most of the Burkitt's lymphomas showed the light chain lambda (7/8). According to the staging classification of Murphy (N Engl J Med 299:1446 1448, 1978), 12% of the 34 cases available were stage IE, 44% stage IIE, 38% stage IIIE, and 6% stage IVE. Of these 34 patients, 13 died with lymphoma within 1 year after diagnosis. The survival rate for the 19 patients in stages I and IIE at 2 years was 83%, while for the 15 patients in stages III and IVE it was 32% (P less than 0.05). A significant difference in survival was found between the 13 patients with primary involvement of the small intestine and the 20 patients with primary involvement of the large intestine and ileocecal region, the latter showing a better prognosis. Lymphoma type did not significantly influence survival. Our findings indicate that the stage at diagnosis and the primary site are important prognostic features in gastrointestinal non-Hodgkin's lymphoma. PMID- 2324164 TI - The therapeutic effect of OK-432-combined adoptive immunotherapy against liver metastases from breast cancer. AB - We studied the therapeutic effect of OK-432 combined with adoptive immunotherapy in 19 cases of liver metastases from breast cancer. Of the 14 patients who received intraarterial OK-432 injection and transfer of cultured lymphocytes, 9 responded to this therapy, whereas no patients responded to intravenous administration. The minimum cell number for a therapeutic response was 8 x 10(8) cells. Metastatic lesions other than those in the liver regressed after therapy in 4 patients. The serum carcinoembryonic antigen level paralleled the therapeutic effect. There were no severe side-effects accompanying this therapy. These results indicate that intraarterial adoptive immunotherapy combined with OK 432 is effective as a new therapeutic approach against liver metastases from breast cancer. PMID- 2324165 TI - The application of age, period and cohort models to predict Swiss cancer mortality. AB - In order to project trends in mortality from 11 major cancer sites in Switzerland to the end of the current century, a log-linear Poisson age/period/cohort model with arbitrary constraints on the parameters was used, fitted to the observed rates for the period 1950-84. One projection was based on the assumption of a total absence of change in the effect of period, the second was based on a linear extrapolation of the logarithms of the seven known periods, and the third was related to a series of a priori external epidemiological hypotheses, whenever available. For instance, coefficients below unity were used for lung and other tobacco-related neoplasms in men, since some decline in exposure to tobacco carcinogens was observed among Swiss men, and above unity for women since the prevalence of smoking has risen among successive generations of women. Although the method has limitations and uncertainties, several qualitative indications could be derived from this exercise. For instance, the various models suggest that the age-standardized mortality from oral cancer in men will probably increase up to the end of the century, even under the optimistic assumption of an appreciable decline in smoking, while cancer of the oesophagus is likely to level off around current values, as other tobacco-related neoplasms, prostate cancer in men, and breast cancer in women will probably do. Some steady decline is predicted by various models fitted to the incidence of stomach and intestinal cancer in both sexes, and to ovarian cancer. Lung cancer will continue to rise in women but will stop rising in men, and it will possibly fall if the hypothesis of a decline in exposure to tobacco carcinogens proves correct. Although any prediction has, by definition, substantial difficulties and uncertainties, projections of cancer mortality in the near future are based on a substantial amount of information already available, and may offer valuable information for epidemiological inferences and health planning purposes. PMID- 2324166 TI - Cancer mortality in young adults: Italy 1955-1985. AB - Although cancer mortality in young adults accounts for only a small proportion of all cancer deaths, it is important since it provides useful indications of the most likely future trends, and relevant information on the role of exposure to specific, or newer, carcinogens. We, therefore, analysed trends in cancer mortality between 1955 and 1985 among Italian men and women aged 20-44 years. In those three decades, overall cancer mortality declined steadily, by 27% in young women (from 33.8 to 24.7/100,000, world standard) but only by 3% (from 27.3 to 26.4/100,000) among men. The decline for men, however, was 16% from the peak rate of 31.5 reached in 1970-1974. The major underlying component causing the different trends in the two sexes was lung and other tobacco-related neoplasms, which had been considerably on the increase in young men up to the early 1970s, and levelled-off thereafter, while showing no appreciable change in women. The falls were about 50% for stomach cancer in both sexes, and over 80% for cervical cancer. A clear impact of improved treatment was reflected in the substantial declines in Hodgkin's disease, of testicular cancer in the last decade and, possibly, in the favourable trends in cancers of the breast, bone, brain and leukemias over the most recent calendar periods. Only two sites showed appreciable and persisting upward trends: oral cavity in men and skin melanoma in both sexes. They therefore constitute priorities for intervention in the near future. PMID- 2324167 TI - Effective chemotherapy for gastrointestinal tumors. 21st Symposium on Recent results in chemotherapy of malignant diseases (Chairmen: J. van de Loo, V. Diehl) of the Gesellschaft zur Bekampfung der Krebskrankheiten Nordrhein-Westfalen (GBK), Dusseldorf, June 1989. AB - Chemotherapy can achieve approximately 50% rates of response, survival advantage or both for every type of gastrointestinal tumor. Findings favor adjuvant therapy for all high-risk tumors. Test-worthy candidate regimens possibly increase safety and efficacy, and challenge traditional choices of treatment for patients with either unresectable or metastatic disease. They create many new options and an unprecedented order of complexity. Treatments remain to be compared and integrated. Efforts to assess the impact of patient characteristics, cost and safety are preliminary at best, and critical to rational usage. There are as yet no perfect regimens, only a series of options supported by incomplete but clearly more promising findings than heretofore. These include: biochemical modulation for gastric and colonic cancer; chemotherapy as a radiotherapy adjuvant for esophageal, rectal, anal, and pancreatic cancer; and immunotherapy for gastric and colorectal cancer. Selective application of endocrine therapy, circadian time schedules or regional therapy may augment safety and quality of life. While response rates have probably improved, their exact frequency, quality and effect on survival are incompletely characterized. Investigations, offer the best way to deal with the options and speed progress, in the context of building upon apparent best therapies. PMID- 2324168 TI - Cytostatic anticancer drug development: preclinical studies and early clinical trials (Frankfurt/Main, November 1989). PMID- 2324169 TI - Implantation response following clinical heart-lung transplantation. AB - Implantation response has been a critical problem following heart-lung and lung transplantation. While the precise etiology of this problem remains unclear, improvements in organ preservation would be expected to have a beneficial effect on implantation response. The time-related profile of the implantation response was studied in 20 patients who underwent heart-lung transplantation between March 1984-March 1987. In 10 operations the donors had intravenous prostaglandin E-1 pretreatment while 10 had no vasodilatation before explantation of the organs. Otherwise lung preservation and early (2 weeks) immunotherapy were similar in both groups. The implantation response was evaluated by chest films and postoperative lung functions and mechanics. Roentgenographic implantation response was evident from the first postoperative day, was less evident at the seventh postoperative day and then gradually increased during the second postoperative week. There was a tendency towards less implantation response in the PGE-1 group than in the control group, but no statistical difference was observed. Patients with severe operative bleeding problems were excluded from the study. Only peak inspiratory pressures were significantly higher in the control group than in the PGE-1 group (p less than 0.01). Other lung function studies (alveolar-capillary pO2 difference, extubation time) were not different in the groups. This study supported the hypothesis that prostaglandin E-1 may have salutary effects on graft preservation and implantation response in heart-lung transplantation. Since 1986, we have performed 16 heart-lung transplantations using graft preservation with PGE-1 and flush perfusion. Thirty-day mortality is 0% and 13 of 16 patients are surviving. PMID- 2324170 TI - Clinical parameters for predicting response to lumbar sympathectomy in patients with severe lower limb ischemia. AB - A prospective study of 85 lumbar sympathectomies for inoperable peripheral vascular disease was conducted to analyze the correlation between lumbar sympathectomy, ankle/arm index (AAI), popliteal-brachial index (PBI), and the clinical presentation; and to study if predicted clinical criteria, single or combined, could be defined for selection of patients who might benefit from lumbar sympathectomy. Good results were obtained if at six months after surgery pain at rest was absent, ischemic ulcers had healed, and there were no major amputations. Seventy-seven percent of all limbs with a preoperative AAI greater than or equal to 0.3 had a good outcome in contrast to 94% failure for index less than 0.3 (p = .000000477). Sixty-nine percent of all limbs with PBI greater than or equal to 0.7 had a good outcome vs. 52% if index less than 0.7 (p = 0.199). Patients with rest pain, simple leg ulcers, and toe gangrene had a good outcome if the AAI greater than or equal to 0.3 and if the postoperative AAI increased by greater than or equal to 0.1. The PBI and diabetic status had no prognostic value. PMID- 2324171 TI - The current role of isolated profundaplasty. AB - The opinions regarding isolated profundaplasty as documented in the literature are divergent, and it is for this reason that we reviewed our results over a 10 year period in order to define the current role for this procedure. The cumulative clinical success rate (both in patient repair and clinical improvement) was 83 +/- 4% at thirty days, 67 +/- 4.8% at one year, 57 +/- 5.9% at two years and 49 +/- 6.8% at three years. The results are best in patients with good tibial outflow (2 or 3 patent vessels), and an early postoperative improvement of ABI greater than 0.10 is predictive of long-term success. Isolated profundaplasty is a good alternative for lower limb revascularization and does not preclude the possibility for distal reconstruction. PMID- 2324172 TI - Superior mesenteric artery aneurysm secondary to infectious endocarditis. AB - A case of superior mesenteric artery aneurysm secondary to infectious endocarditis is presented. Although selective angiography was necessary to detect the shape and precise location of the aneurysm, non-invasive diagnostic techniques including ultrasonography and computed tomography were also useful in detecting the aneurysm and planning the management of this unusual condition. Mitral valve replacement and aneurysmorrhaphy with bypass grafting of the superior mesenteric artery were successfully performed. PMID- 2324173 TI - Surgery for an isolated aneurysm of the internal iliac artery. Report of three cases. AB - Three cases of isolated internal iliac artery aneurysm are reported. The patients, aged 89, 79, and 61, were all males. All three aneurysms were on the left side, and two of them had ruptured. Arterial reconstruction was performed in all three cases. Prompt diagnosis by computed tomography followed by an early operation is recommended for this extremely rare and often fatal lesion. PMID- 2324174 TI - Aortobipopliteal bypass via the obturator foramina. AB - Patients with aortoiliac disease who have successive occlusion of aortofemoral bypass, femoro-femoral bypass, axillo-femoral bypass, and multiple thrombectomies have a very poor prognosis. In these patients, amputation is frequently inevitable and wound healing is often a problem. Aortobipopliteal bypass via the obturator foramina, without disturbing the collateral vessels which are unsuitable for bypass at the groin, is an alternate approach in the management of this type of patient. Three cases have been successfully constructed using dacron (No. 1) or PTFE (No. 2) prostheses with improvement of ankle brachial indices (0.3-0.6). One graft was patent for five years before occlusion of one limb. Two grafts have remained patent since 1983. PMID- 2324175 TI - Nine year patent femorotibial expanded polytetrafluoroethylene graft bypass. AB - A 65-year-old patient with a trophic lesion and severe intermittent claudication in the right lower extremity was surgically treated by femoro-distal-tibial bypass employing a prosthetic 6 mm diameter PTFE (Gore-Tex) graft. It is still patent nine years later as shown by a follow-up arteriogram. The patient's trophic lesion disappeared, and there are presently no symptoms of intermittent claudication. When arterial revascularization in the leg is indicated, an option to a saphenous vein graft for long bypass is the use of a PTFE graft. PMID- 2324176 TI - The effect of potassium phosphate, magnesium chloride and T6 as blocking agents on tissue valve calcification. PMID- 2324177 TI - Closed mitral valvotomy in the older subject. Results in 367 consecutive patients. AB - To determine the safety, efficacy, operative mortality, and long-term results, we reviewed 367 patients with mitral stenosis above the age of 40 who underwent mitral valvotomy. In this study, the majority of the subjects belonged to functional Class III and IV (97%) of the New York Heart Association (NYHA). Atrial fibrillation was associated in 38 percent and mitral valve calcification in 24 percent. The hospital mortality was 6.3 percent. Only 1 patient developed severe mitral regurgitation requiring emergency valve replacement. Early postoperative embolism occurred in only 1% of those who were in atrial fibrillation and had preoperative anticoagulation. Long-term results indicate an 85.6 percent survival at the end of 24 years with a very low incidence of restenosis. Late death occurred in 4.6%. These findings support our continuing experience and impression that closed transventricular valvotomy remains the most effective palliative operation in the treatment of most patients with mitral stenosis. With the increasing need for cost containment in health care, this technique of closed transventricular valvotomy assumes even greater importance. PMID- 2324178 TI - Aortocoronary bypass results: a discriminant multivariate analysis of risk factors of operative mortality. AB - Clinical results of coronary artery bypass surgery have been evaluated analyzing operative mortality and its related risk factors. Four hundred and thirty seven consecutive patients undergoing coronary artery bypass surgery between January 1979, and December 1983, form the clinical material of this study. The gender of patients was male in 89% of the cases, the age ranged from 34 to 78 years with a mean of 54.8 +/- 8.2 (SD); patients with combined surgical procedures were excluded. The operative mortality was 5.49% (24 patients); no significant difference was found between years of the observation period. Death was due to cardiac causes in 75% of cases. Statistical analysis carried on 14 clinical, angiographic and surgical variables identified as significant risk factors of operative mortality age (p = 0.002) and cross-clamp time (p = 0.016). Both of these increased their weight when entered in a stepwise logistic regression. The EF also showed a value close to statistical significance (p = 0.06). PMID- 2324179 TI - Coronary artery surgery in Asian patients. AB - We studied retrospectively, 412 consecutive Asian patients undergoing coronary artery bypass grafting between January 1st, 1982 and June 30th, 1987. The mean age was 55 +/- 9 years at operation with a 70.5% male predominance. Patients of Chinese origin accounted for 60.9%, Indonesian for 26.4%, Indian 9.9% and Malaysian 2.6%. Chronic stable angina was the most consistent presenting symptom in 71% and 49% had at least one myocardial infarction in the past. Fifty percent were hypertensive and 26% diabetic. Left main stem coronary artery obstruction was evident in 21.6% and the coronary arteries diffusely diseased in 53%. An average of 3.8 +/- 0.4 grafts were performed per patient using reversed saphenous vein, and endarterectomies were necessitated in 27.1%. The small calibre of coronary arteries in Asian patients was reflected by 54% of grafted vessels having a luminal diameter of 1.5 mm. The early mortality rate and the peri operative myocardial infarction rate was 1.2% in each instance. A mean follow-up of 30 months revealed a late mortality of 1.9% and 76% of patients were in NYHA Functional Class I. This study suggests that despite a high incidence of hypertension, diabetes and diffuse coronary artery disease Asian patients tolerate coronary artery bypass graft surgery well and obtain significant benefit from it. PMID- 2324180 TI - Surgical treatment of subvalvular aortic stenosis. Long-term results. AB - From 1966 till May 1988, 53 patients underwent surgery for fixed subaortic stenosis. Subvalvular obstruction was isolated in 27 patients (Group I) and associated with aortic valve lesions in 26 (Group II). A membranous stricture was documented in 5 patients and a fibromuscular ring in 48. Excision of the ring and myectomy were performed in all patients, and an associated aortic valve replacement or reconstruction in 7 and 4 patients respectively. There were no hospital deaths. Follow-up evaluation in 50 patients ranged from 6 months to 22 years. Eight patients had to be reoperated upon (1 from group I, 7 from group II): aorto-ventriculoplasty was performed in 3, aortic valve replacement with redo myectomy in 3 and mitro-aortic valve replacement in 2. One of them had 2 reoperations. Functional status at the time of the last outpatient visit was most satisfactory. Continued evaluation remains necessary as obstruction may reappear despite the absence of symptoms. PMID- 2324181 TI - Dysfunction of a Duromedics valve in the tricuspid position. Case report. AB - Tricuspid dysfunction appeared in a 47 year-old woman fifteen months after multiple valvular surgery, including aortic and tricuspid valvular replacement with Duromedics valves. At reoperation one of the leaflets of the tricuspid prosthesis was blocked with overgrown tissue from the native tricuspid annulus. The prosthesis was replaced with another Duromedics valve and the patient is doing well nineteen months later. This case, is the first report of dysfunction of a Duromedics mechanical cardiac valve inserted in the tricuspid position. PMID- 2324182 TI - Survival following outlet strut fracture of a Bjork-Shiley mitral prosthesis. Report of two cases. AB - Late outlet strut fracture occurred in two patients with the 27 mm Bjork-Shiley 60 degrees Convexo-Concave mitral prosthesis. Both patients exhibited symptoms that appeared to precede strut fracture and both survived reoperation. PMID- 2324183 TI - Compression of an anomalous left circumflex coronary artery by a bioprosthetic valve ring. AB - The most common anomaly of the coronary arteries is the origin of the left circumflex artery from the right sinus of Valsalva or the right coronary artery proper. This anomaly is rarely clinically significant. A patient is reported here who has such an anomaly which did become clinically significant after a bioprosthetic aortic valve replacement. The circumflex artery described here became compressed between the Hancock aortic valvular ring and the mitral valvular apparatus. This case is the first antemortem report of such a compression to be demonstrated angiographically and the first case to be the results of an aortic bioprosthetic ring alone. Special surgical considerations must be made when performing valvular replacements on patients with this coronary artery anomaly. PMID- 2324184 TI - Successful removal of a cardiac fibroma in an elderly patient. AB - Successful removal of a cardiac fibroma of the left ventricular free wall in a 76 year-old male is reported. The rarity of this tumor in the elderly and diagnostic clues are discussed. PMID- 2324185 TI - Antiplatelet therapy and carotid plaque hemorrhage and its clinical implications. AB - One hundred and fifty-four carotid endarterectomy plaques were studied to determine the correlation of multiple intraplaque hemorrhages to (1) carotid symptoms, (2) the percentage of carotid stenosis, and (3) the preoperative antiplatelet therapy. The plaques were evaluated histopathologically for the presence of multiple hemorrhages. The data were analyzed using the chi 2 test. Multiple hemorrhages were noted in 60.4% and single or not hemorrhage in 39.6% of patients with hemispheric symptoms. In patients with nonhemispheric symptoms, 9.4% had multiple hemorrhages and 90.6% has single or no hemorrhages; 89.4% plaques with multiple hemorrhages had stenosis greater than 75% in contrast to 37.5% in plaques with single or no hemorrhage; and 62.5% with single or no hemorrhage had stenosis of less than 75% (p less than 0.001). In patients receiving antiplatelet therapy, 80.1% of plaques with multiple hemorrhages were removed, in contrast to 19.7% from patients not receiving antiplatelets (p less than 0.001). IN CONCLUSION: Multiple intraplaque hemorrhages were seen more often in patients with hemispheric symptoms and are associated with more critical carotid stenosis. Preoperative antiplatelet therapy increases the incidence of repeated plaque hemorrhages; therefore, we question the validity of this therapy in certain patients with carotid disease. PMID- 2324186 TI - Results of Mustard's repair for dextro-transposition of the great arteries. AB - Dextro-Transposition of Great Arteries (d-TGA) was repaired by Mustard's operation in 69 patients during a 10 year period (1973-1982) in our institution. Ages at the time of surgery ranged from 3 months to 18 years, with a median age of 18 months. Factors that most affected mortality and morbidity were associated cardiac defect, the year of the operation and the age of the patient. Of the 69 patients, 26 (38%) had complex d-TGA. Early post-operative mortality was 2.38% for patients with simple transposition and 22% for the complex group. All early deaths occurred in the early part of series. Ten consecutive cases with complex transpositions in the late part of the series have done well. There were 5 late deaths--4 from the early series and these had complex transposition. Postoperative non-fatal complications included arrhythmia which occurred in 6 patients (9%). The rhythm abnormality was temporary in 2 and permanent pacing was required in 2 other patients (2.9%). There were 3 cases of late caval obstruction and 4 cases of late pulmonary venous obstruction--six of these seven patients were less then 12 months of age. Postoperative renal failure occurred in patients in the early series but was not seen in the late series. Three children developed postoperative pulmonary edema due to large bronchial collateral arteries and underwent successful collateral vessel ligation subsequent to the Mustard operation. Two patients have demonstrated late tricuspid regurgitation, are presently in heart failure and may need valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324187 TI - Abdominal aortic aneurysmectomy in octogenarian patients. AB - The authors report 56 patients. 80 years of age or older who had an abdominal aortic aneurysm (AAA): twenty seven were operated upon as emergencies, 7 with intra-peritoneal (Group I) and 20 with retro-peritoneal rupture (Group II). Twenty nine underwent elective surgery (Group III). Renal pulmonary and cardiac disease are frequent in octogenarian patients. The surgical repair consisted of 40 knitted bifurcated grafts and 16 aorto-aortic woven grafts. The overall in hospital mortality rate is high (28.5%: 16 patients) essentially in "emergency" surgery: 71% for the seven Group I patients and 45% for the twenty Group II patients. The in-hospital mortality rate of 6.9% for the Group III of "elective" procedure is higher than the mortality rate of patients of all ages operated on for asymptomatic AAA in our institution which is 4.3%. Once a patient has been operated on successfully his life expectancy tends to parallel that of a normal population for his age group. These results can be improved with preventive measures such as elective surgery for asymptomatic AAA with a diameter of 6 cm or more. Operative contraindications are severe congestive heart failure, advanced pulmonary disease or neoplastic disease. The age "per se" is not a contraindication to aneurysmectomy. Physiologic rather than chronologic age should determine the selection for AAA in the over-80 age group. CT scans and MR are safe fast and non-invasive preoperative examinations for AAA. PMID- 2324188 TI - Proximal anastomosis in aortobifemoral bypass: end-to-end or end-to-side? AB - When performing an aortobifemoral bypass, the surgeon may choose between an end to-end or end-to-side aortic anastomosis. Although several authors have claimed the superiority of the former, controversy still exists. The aim of this study was to compare the early and late results of these two techniques in patients for which both procedures were possible. Of 158 patients, aortic anastomosis was performed end-to-end in 47 (group I) and end-to-side in 111 (group II). Both groups were similar in all other aspects. The type of proximal anastomosis did not affect the rate of perioperative mortality or early thrombosis. There were no secondary aortic aneurysms or aortoenteric fistulae in either group. Actuarial primary (without reoperation) and secondary (after thrombectomy) five year patency rates were 90.2 and 98.9 per cent in group I, and 90.8 and 98.5 per cent in group II, respectively. Five-year limb survival was 95.3 and 95.7 per cent, respectively. As we could not find any difference between the results in the two groups, we suggest choosing the simplest procedure which maintains adequate pelvic and colonic blood supply, according to angiographic findings. PMID- 2324189 TI - The management of aortoenteric and paraprosthetic fistulae. AB - Aortoenteric and aortic paraprosthetic fistulae are devastating complications. Most authors recommend total excision of the graft and revascularization of the lower extremities by extra-anatomic bypass. We reviewed the University of Pittsburgh experience with these fistulae in 15 patients between 1977 and 1987. There were 9 aortoenteric fistulae (AEF) and 6 paraprosthetic fistulae (PPF). Seven of the 9 AEF had no abscess surrounding the graft, but communication of the intestine with the aortic anastomosis. One patient died during operation. Six patients underwent a local repair or in situ replacement of the graft. All 6 of those patients survived operation without limb loss. Two of the 9 patients with AEF had evidence of graft infection and underwent total excision of the graft and extra-anatomic reconstruction. Both patients died, one of sepsis and one of aortic stump rupture. All 6 patients with PPF had clinical and operative evidence of overt graft infection and underwent total graft excision and extra-anatomic bypass. Two of these patients died secondary to sepsis. We conclude that AEF, without evidence of graft infection, were safely treated by local repair. Patients with PPF had infected grafts requiring graft removal with significant morbidity and mortality. PMID- 2324190 TI - Atherothrombotic microembolism of the lower extremities (the blue toe syndrome) from atherosclerotic non-aneurysmal aortic plaques. AB - Six patients with no hemodynamically significant atherosclerotic lesions of the lower limb arteries but with ischemic changes of the feet or toes were studied and diagnosed as having atherothrombotic microembolism. All patients were non claudicators and had peripheral Doppler examinations on admission. Five patients experienced more than one separate episode of microembolization involving both extremities. None presented with a history of heart disease or diabetes. Biplanar arteriograms revealed in every case atherosclerotic degeneration of the aorta without any obstructing lesions and anatomical arterial continuity between the aorta and the site of distal embolization. Three patients who refused operation, were treated conservatively, with a combination of dipyridamole plus aspirin. Three other patients had surgical repair of their atheromatous infrarenal aorta: in two cases thromboendarterectomy was performed, and in the other a Dacron bifurcated graft interposition. No amputations resulted in the patients treated medically, but one of the surgical group lost one toe. This study confirms that atherothrombotic microembolism from an ulcerated atherosclerotic aorta is a potential threat to the extremities and indicates that the optimal therapy for this syndrome has yet to be found. PMID- 2324191 TI - Viability of long-term cryopreserved human saphenous veins. AB - The feasibility of maintaining long-term viability of human venous allografts by cryopreservation has been investigated. Segments of vein were obtained from 85 patients undergoing a stripping operation for varicose veins. The venous segments were immersed in a dimethylsulfoxide 15% solution, deep frozen at -196 degrees C in liquid nitrogen and preserved for a duration of 1 week to 24 months. Light microscopy (n = 126) failed to demonstrate striking differences between control veins and any of the cryopreserved veins. The types of damage observed at scanning electron microscopy included endothelial cell separation, endothelial cell loss, exposed basement membrane and exposed fibrillar collagen, which were graded on a scale. The score for short term (less than 3 weeks) stored veins was 8.1 +/- 0.9 (mean +/- SEM) and did not differ from the long-term (greater than 10 weeks) stored veins score (6.3 +/- 1.0, p NS). The tissue enzymes LDH, GOT, GPT, CPK were measured in the frozen vein groups (n = 115) after thawing to room temperature. Cryopreservation did not alter any of the tissue enzymes measured when compared to controls. Endothelial fibrinolytic activity (FA) of 58 venous segments cryopreserved for a mean duration of 20 months was 6136.4 +/- 292.1 Tissue Activator Units (TAU) and did not differ from FA of 11 controls (5989.1 +/ 696.8 TAU). Synthesis of 6-Keto-PGF1-alpha-2, a stable breakdown product of PGI2, measured in 10 venous segments cryopreserved for 10 months, was significantly higher than in 13 veins stored in saline for 12 hours at 4 degrees C (2.8 +/- 0.4 vs 0.4 +/- 0.1 PG ml-1mg-1min-1, respectively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324192 TI - Chemoattractant-stimulated polymorphonuclear leukocytes contain two populations of actin filaments that differ in their spatial distributions and relative stabilities. AB - Chemoattractants stimulate actin polymerization in lamellipodia of polymorphonuclear leukocytes. We find that removal of chemoattractant results in rapid (within 10 s at 37 degrees C) and selective depolymerization of the F-actin located in lamellipodia. Addition of 10 microM cytochalasin B, in the presence of chemoattractant, also resulted in rapid and selective depolymerization of lamellar F-actin. The elevated F-actin level induced by chemoattractant rapidly returns to the level present in unstimulated cells after (a) a 10-fold decrease in chemoattractant concentration; (b) the addition of 10 microM cytochalasin B; or (c) cooling to 4 degrees C. The F-actin levels of unstimulated cells are only slightly affected by these treatments. Based on the similar effects of cytochalasin addition and chemoattractant dilution, it is likely that both treatments result in actin depolymerization from the pointed ends of filaments. Based on our results we propose that chemoattractant-stimulated polymorphonuclear leukocytes contain two distinct populations of actin filaments. The actin filaments within the lamellipodia are highly labile and in the continued presence of chemoattractant these filaments are rapidly turning over, continually polymerizing at their plus (barbed) ends, and depolymerizing at their minus ends. In contrast, the cortical F-actin filaments of both stimulated and unstimulated cells are differentially stable. PMID- 2324193 TI - Mechanism of the formation of contractile ring in dividing cultured animal cells. I. Recruitment of preexisting actin filaments into the cleavage furrow. AB - Cytokinesis of animal cells involves the formation of the circumferential actin filament bundle (contractile ring) along the equatorial plane. To analyze the assembly mechanism of the contractile ring, we microinjected a small amount of rhodamine-labeled phalloidin (rh-pha) or rhodamine-labeled actin (rh-actin) into dividing normal rat kidney cells. rh-pha was microinjected during prometaphase or metaphase to label actin filaments that were present at that stage. As mitosis proceeded into anaphase, the labeled filaments became associated with the cortex of the cell. During cytokinesis, rh-pha was depleted from polar regions and became highly concentrated into the equatorial region. The distribution of total actin filaments, as revealed by staining the whole cell with fluorescein phalloidin, showed a much less pronounced difference between the polar and the equatorial regions. The sites of de novo assembly of actin filaments during the formation of the contractile ring were determined by microinjecting rh-actin shortly before cytokinesis, and then extracting and fixing the cell during mid cytokinesis. Injected rhodamine actin was only slightly concentrated in the contractile ring, as compared to the distribution of total actin filaments. Our results indicate that preexisting actin filaments, probably through movement and reorganization, are used preferentially for the formation of the contractile ring. De novo assembly of filaments, on the other hand, appears to take place preferentially outside the cleavage furrow. PMID- 2324194 TI - Dynamic organization of ATP and birefringent fibrils during free locomotion and galvanotaxis in the plasmodium of Physarum polycephalum. AB - Directed migration by a cell is a good phenomenon for studying intracellular coordination. Dynamic organization of both ATP and birefringent fibrils throughout the cell was studied in the multinuclear ameboid cell of the Physarum plasmodium during free locomotion and galvanotaxis. In a directionally migrating plasmodium, waves of ATP as well as thickness oscillations propagated from just inside the advancing front to the rear, and ATP concentration was high at the front on the average. In a DC electric field, locomotion was inhibited more strongly, ATP concentration decreased more, and birefringent fibrils were formed more abundantly at the anodal than at the cathodal side. Inside the cell there were a few undulations in the distributions of ATP and birefringent fibrils. In short, birefringent fibrils become abundant where ATP concentration decreases. The possible mechanism of the coordination in the directed migration and the implications of the scaling law are discussed. PMID- 2324196 TI - Nucleus-associated microtubules help determine the division plane of plant epidermal cells: avoidance of four-way junctions and the role of cell geometry. AB - To investigate the spatial relationship between the nucleus and the cortical division site, epidermal cells were selected in which the separation between these two areas is large. Avoiding enzyme treatment and air drying, Datura stramonium cells were labeled with antitubulin antibodies and the three dimensional aspect of the cytoskeletons was reconstructed using computer-aided optical sectioning. In vacuolated cells preparing for division, the nucleus migrates into the center of the cell, suspended by transvacuolar strands. These strands are now shown to contain continuous bundles of microtubules which bridge the nucleus to the cortex. These nucleus-radiating microtubules adopt different configurations in cells of different shape. In elongated cells with more or less parallel side walls, oblique strands radiating from the nucleus to the long side walls are presumably unstable, for they are progressively realigned into a transverse disc (the phragmosome) as broad, cortical, preprophase bands (PPBs) become tighter. The phragmosome and the PPB are both known predictors of the division plane and our observations indicate that they align simultaneously in elongated epidermal cells. These observations suggest another hypothesis: that the PPB may contain microtubules polymerized from the nuclear surface. In elongated cells, the majority of the radiating microtubules, therefore, come to anchor the nucleus in the transverse plane, consistent with the observed tendency of such cells to divide perpendicular to the long axis. In nonrectangular isodiametric epidermal cells, which approximate regular hexagons in section, the radial microtubular strands emanating from the nucleus tend to remain associated with the middle of each subtending cell wall. The strands are not reorganized into a single dominant transverse bar, but remain as a starlike array until mitosis. PPBs in these cells are not as tight; they may only be a sparse accumulation of microtubules, even forming along non-diametrical radii. This arrangement is consistent with the irregular division patterns observed in epidermal mosaics of isodiametric D. stramonium cells. The various conformations of the radial strands can be modeled by springs held in two-dimensional hexagonal frames, and by soap bubbles in three-dimensional hexagonal frames, suggesting that the division plane may, by analogy, be selected by minimal path criteria. Such behavior offers a cytoplasmic explanation of long-standing empirically derived "rules" which state that the new cell wall tends to meet the maternal wall at right angles. The radial premitotic strands and their analogues avoid taking the longer path to the vertex of an angle where a cross wall is already present between neighboring cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2324195 TI - Inositol 1,4,5-trisphosphate-induced calcium release in the organelle layers of the stratified, intact egg of Xenopus laevis. AB - Using double-barreled, Ca2(+)-sensitive microelectrodes, we have examined the characteristics of the Ca2+ release by inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) in the various layers of Xenopus laevis eggs in which the organelles had been stratified by centrifugation. Centrifugation of living eggs stratifies the organelles yet retains them in the normal cytoplasmic milieu. The local increase in intracellular free Ca2+ in each layer was directly measured under physiological conditions using theta-tubing, double-barreled, Ca2(+) sensitive microelectrodes in which one barrel was filled with the Ca2+ sensor and the other was filled with Ins(1,4,5)P3 for microinjection. The two tips of these electrodes were very close to each other (3 microns apart) enabling us to measure the kinetics of both the highly localized intracellular Ca2+ release and its subsequent removal in response to Ins(1,4,5)P3 injection. Upon Ins(1,4,5)P3 injection, the ER-enriched layer exhibited the largest release of Ca2+ in a dosage-dependent manner, whereas the other layers, mitochondria, lipid, and yolk, released 10-fold less Ca2+ in a dosage-independent manner. The removal of released Ca2+ took place within approximately 1 min. The sensitivity to Ins(1,4,5)P3 and the time course of intracellular Ca2+ release in the unstratified (unactivated) egg is nearly identical to that observed in the ER layer of the stratified egg. Our data suggest that the ER is the major organelle of the Ins(1,4,5)P3-sensitive Ca2+ store in the egg of Xenopus laevis. PMID- 2324197 TI - Purified N-cadherin is a potent substrate for the rapid induction of neurite outgrowth. AB - N-cadherin is the predominant mediator of calcium-dependent adhesion in the nervous system (Takeichi, M. 1988. Development (Camb.). 102: 639-655). Investigations using antibodies to block N-cadherin function (Bixby, J.L., R.L. Pratt, J. Lilien, and L.F. Reichardt. 1987. Proc. Natl. Acad. Sci. USA. 84:2555 2569; Bixby, J.L., J. Lilien, and L.F. Reichardt. 1988. J. Cell Biol. 107:353 362; Tomaselli, K.J., K.N. Neugebauer, J.L. Bixby, J. Lilien, and L.F. Reichardt. 1988. Neuron. 1:33-43) or transfection of the N-cadherin gene into heterologous cell lines (Matsunaga, M., K. Hatta, A. Nagafuchi, and M. Takeichi. 1988. Nature (Lond.). 334:62-64) have provided evidence that N-cadherin, alone or in combination with other molecules, can participate in the induction of neurite extension. We have developed an affinity purification procedure for the isolation of whole N-cadherin from chick brain and have used the isolated protein as a substrate for neurite outgrowth. N-cadherin promotes the rapid extension of neurites from chick ciliary ganglion neurons, which extend few or no neurites on adhesive but noninducing substrates such as polylysine, tissue culture plastic, and collagens. N-cadherin is extremely potent, more so than the L1 adhesion molecule, and comparable to the extracellular matrix protein laminin. Compared to laminin, however. N-cadherin promotes outgrowth from ciliary ganglion neurons extremely rapidly and with a distinct morphology. These results provide a direct demonstration that N-cadherin is sufficient to induce neurite outgrowth when substrate bound and suggest that the mechanism(s) involved may differ from that induced by laminin. PMID- 2324198 TI - Neurothelin: an inducible cell surface glycoprotein of blood-brain barrier specific endothelial cells and distinct neurons. AB - The blood-brain barrier is characterized by still poorly understood barrier and transport functions performed by specialized endothelial cells. Hybridoma technology has been used to identify a protein termed neurothelin that is specific for these endothelial cells. Neurothelin is defined by the species specific mouse mAb 1W5 raised against lentil-lectin-binding proteins of neural tissue from embryonic chick. In the posthatch chick, neurothelin expression is found on endothelial cells within the brain but not on those of the systemic vascular system. Injection of the monoclonal antibody in vivo leads to labeling of brain capillaries, indicating that the corresponding antigen is expressed on the luminal surface of brain endothelial cells. Transplantation of embryonic mouse brain onto the chick chorioallantoic membrane results in rodent brain vascularization by the avian vascular system. Subsequently, normally mAb 1W5 negative endothelial cells, originating from blood vessels of the chick chorioallantoic membrane, are induced to express neurothelin when they are in contact with mouse neural tissue. In contrast to differentiated brain neurons that do not express neurothelin, neurons of the nonvascularized chick retina synthesize neurothelin. However, neurothelin is not found on retinal ganglion cell axons terminating on 1W5-negative brain cells. 1W5 immunoreactivity was also found in the pigment epithelium that forms the blood-eye barrier. Putting epithelial cells into culture results in concentration of neurothelin at cell cell contact sites, leaving other cell surface areas devoid of antigen. Therefore, the distribution of neurothelin appears to be regulated by cell-cell interactions. In Western blot analysis, neurothelin was identified as a protein with a molecular mass of approximately 43 kD. The protein bears at least one intramolecular disulfide bridge and sulfated glucuronic acid as well as alpha-D substituted mannose/glucose moieties. The exclusive neurothelin expression in the posthatch chick on endothelial cells of the central nervous system but not on systemic endothelial cells makes neurothelin a marker specific for blood-brain barrier-forming endothelial cells. The spatiotemporally regulated neurothelin expression in neurons suggests an interaction between vascularization and neuronal differentiation. PMID- 2324199 TI - Ca2+ transients are not required as signals for long-term neurite outgrowth from cultured sympathetic neurons. AB - A method for clamping cytosolic free Ca2+ ([Ca2+]i) in cultures of rat sympathetic neurons at or below resting levels for several days was devised to determine whether Ca2+ signals are required for neurite outgrowth from neurons that depend on Nerve Growth Factor (NGF) for their growth and survival. To control [Ca2+]i, normal Ca2+ influx was eliminated by titration of extracellular Ca2+ with EGTA and reinstated through voltage-sensitive Ca2+ channels. The rate of neurite outgrowth and the number of neurites thus became dependent on the extent of depolarization by KCl, and withdrawal of KCl caused an immediate cessation of growth. Neurite outgrowth was completely blocked by the L type Ca2+ channel antagonists nifedipine, nitrendipine, D600, or diltiazem at sub- or micromolar concentrations. Measurement of [Ca2+]i in cell bodies using the fluorescent Ca2+ indicator fura-2 established that optimal growth, similar to that seen in normal medium, was obtained when [Ca2+]i was clamped at resting levels. These levels of [Ca2+]i were set by serum, which elevated [Ca2+]i by integral of 30 nM, whereas the addition of NGF had no effect on [Ca2+]i. The reduction of [Ca2+]o prevented neurite fasciculation but this had no effect on the rate of neurite elongation or on the number of extending neurites. These results show that neurite outgrowth from NGF-dependent neurons occurs over long periods in the complete absence of Ca2+ signals, suggesting that Ca2+ signals are not necessary for operating the basic machinery of neurite outgrowth. PMID- 2324200 TI - Signal transduction for chemotaxis and haptotaxis by matrix molecules in tumor cells. AB - Transduction of signals initiating motility by extracellular matrix (ECM) molecules differed depending on the type of matrix molecule and whether the ligand was in solution or bound to a substratum. Laminin, fibronectin, and type IV collagen stimulated both chemotaxis and haptotaxis of the A2058 human melanoma cell line. Peak chemotactic responses were reached at 50-200 nM for laminin, 50 100 nM for fibronectin, and 200-370 nM for type IV collagen. Checkerboard analysis of each attractant in solution demonstrated a predominantly directional (chemotactic) response, with a minor chemokinetic component. The cells also migrated in a concentration-dependent manner to insoluble step gradients of substratum-bound attractant (haptotaxis). The haptotactic responses reached maximal levels at coating concentrations of 20 nM for laminin and type IV collagen, and from 30 to 45 nM for fibronectin. Pretreatment of cells with the protein synthesis inhibitor, cycloheximide (5 micrograms/ml), resulted in a 5-30% inhibition of both chemotactic and haptotactic responses to each matrix protein, indicating that de novo protein synthesis was not required for a significant motility response. Pretreatment of cells with 50-500 micrograms/ml of synthetic peptides containing the fibronectin cell-recognition sequence GRGDS resulted in a concentration-dependent inhibition of fibronectin-mediated chemotaxis and haptotaxis (70-80% inhibition compared to control motility); negative control peptide GRGES had only a minimal effect. Neither GRGDS nor GRGES significantly inhibited motility to laminin or type IV collagen. Therefore, these results support a role for the RGD-directed integrin receptor in both types of motility response to fibronectin. After pretreatment with pertussis toxin (PT), chemotactic responses to laminin, fibronectin, and type IV collagen were distinctly different. Chemotaxis to laminin was intermediate in sensitivity; chemotaxis to fibronectin was completely insensitive; and chemotaxis to type IV collagen was profoundly inhibited by PT. In marked contrast to the inhibition of chemotaxis, the hepatotactic responses to all three ligands were unaffected by any of the tested concentrations of PT. High concentrations of cholera toxin (CT; 10 micrograms/ml) or the cAMP analogue, 8-Br-cAMP (0.5 mM), did not significantly affect chemotactic or haptotactic motility to any of the attractant proteins, ruling out the involvement of cAMP in the biochemical pathway initiating motility in these cells. The sensitivity of chemotaxis induced by laminin and type IV collagen, but not fibronectin, to PT indicates the involvement of a PT-sensitive G protein in transduction of the signals initiating motility to soluble laminin and type IV collagen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2324201 TI - Correlation between structure and mass distribution of the nuclear pore complex and of distinct pore complex components. AB - Nuclear pore complexes (NPCs) prepared from Xenopus laevis oocyte nuclear envelopes were studied in "intact" form (i.e., unexposed to detergent) and after detergent treatment by a combination of conventional transmission electron microscopy (CTEM) and quantitative scanning transmission electron microscopy (STEM). In correlation-averaged CTEM pictures of negatively stained intact NPCs and of distinct NPC components (i.e., "rings," "spoke" complexes, and "plug spoke" complexes), several fine structural features arranged with octagonal symmetry about a central axis could reproducibly be identified. STEM micrographs of unstained/freeze-dried intact NPCs as well as of their components yielded comparable but less distinct features. Mass determination by STEM revealed the following molecular masses: intact NPC with plug, 124 +/- 11 MD; intact NPC without plug, 112 +/- 11 MD; heavy ring, 32 +/- 5 MD; light ring, 21 +/- 4 MD; plug-spoke complex, 66 +/- 8 MD; and spoke complex, 52 +/- 3 MD. Based on these combined CTEM and STEM data, a three-dimensional model of the NPC exhibiting eightfold centrosymmetry about an axis perpendicular to the plane of the nuclear envelope but asymmetric along this axis is proposed. This structural polarity of the NPC across the nuclear envelope is in accord with its well-documented functional polarity facilitating mediated nucleocytoplasmic exchange of molecules and particles. PMID- 2324202 TI - Fatty acylation promotes fusion of transport vesicles with Golgi cisternae. AB - Two different methods, stimulation of transport by fatty acyl-coenzyme A (CoA) and inhibition of transport by a nonhydrolyzable analogue of palmitoyl-CoA, reveal that fatty acylation is required to promote fusion of transport vesicles with Golgi cisternae. Specifically, fatty acyl-CoA is needed after the attachment of coated vesicles and subsequent uncoating of the vesicles, and after the binding of the NEM-sensitive fusion protein (NSF) to the membranes, but before the actual fusion event. We therefore suggest that an acylated transport component participates, directly or indirectly, in membrane fusion. PMID- 2324204 TI - Factors influencing the performance of peptide mapping by reversed-phase high performance liquid chromatography. AB - Factors controlling the performance of peptide mapping on reversed-phase columns were systematically evaluated. Performance criteria included resolution (peak capacity and selectivity), system reproducibility, sensitivity and analysis speed. Column configuration, characteristics of packing materials, mobile phase composition, operating variables and instrumental designs were found to influence the performance of peptide mapping. Considerations for peptide identification techniques are discussed. PMID- 2324205 TI - Binary and ternary salt gradients in hydrophobic-interaction chromatography of proteins. AB - Hydrophobic-interaction chromatography of mixtures of acidic and basic proteins having a wide range of molecular weights and hydrophobic character was carried out by using binary and ternary salt gradients. Chaotropic and antichaotropic salts as well as organic salts were incorporated in the eluents. The stationary phase consisted of macroporous silica with surface-bound polyether moieties. At constant eluent surface tension, gradient elution with two or three aqueous salt solutions was found to be superior to single-salt gradients in modulating hydrophobic-interaction chromatography retention and selectivity. The effect was attributed to the competitive salt-specific binding to the protein molecule and/or the stationary phase surface. Chaotropic/antichaotropic salt gradient systems exhibited vastly different selectivities upon changing the nature and concentrations of salts in the eluents. In general, the retention of basic proteins increased while that of acidic proteins either decreased or remained unchanged with the use of chaotropic salts. At the same surface tension of the eluent, KSCN and KC1O4 yielded different selectivities. The addition of organic salts, such as tetrabutylammonium bromide was found to be suitable for the separation of proteins having a wide range of isoelectric points. PMID- 2324206 TI - Unexpected elution behaviour of peptides with various reversed-phase columns. AB - Gastrin and cholecystokinin peptides were separated by reversed-phase chromatography on conventional bristle-type and polymer-coated stationary phases. The retention of the sulphated and non-sulphated isomeric forms of both peptides is governed by the structure of the peptide, the net charge and additional polar interactions with the stationary phases. Polymer-coated phases are optimum for separations according to chain length, whereas polar interactions are required for the separation of sulphated and non-sulphated peptides of identical chain length. PMID- 2324203 TI - Conversion of a class II integral membrane protein into a soluble and efficiently secreted protein: multiple intracellular and extracellular oligomeric and conformational forms. AB - The NH2 terminus of the F1 subunit of the paramyxovirus SV5 fusion protein (fusion related external domain; FRED) is a hydrophobic domain that is implicated as being involved in mediating membrane fusion. We have examined the ability of the FRED to function as a combined signal/anchor domain by substituting it for the natural NH2-terminal signal/anchor domain of a model type II integral membrane protein: the hybrid protein (NAF) was expressed in eukaryotic cells. The FRED was shown to act as a signal sequence, targeting NAF to the lumen of the ER, by the fact that NAF acquired N-linked carbohydrate chains. Alkali fractionation of microsomes indicated that NAF is a soluble protein in the lumen of the ER, and the results of NH2-terminal sequence analysis showed that the FRED is cleaved at a site predicted to be recognized by signal peptidase. NAF was found to be efficiently secreted (t1/2 approximately 90 min) from the cell. By using a combination of sedimentation velocity centrifugation and immunoprecipitation assays using polyclonal and conformation-specific monoclonal antibodies it was found that extracellular NAF consisted of a mixture of monomers, disulfide-linked dimers, and tetramers. The majority of the extracellular NAF molecules were not reactive with the conformation-specific monoclonal antibodies, suggesting they were not folded in a native form and that only the NAF tetramers had matured to a native conformation such that they exhibited NA activity. The available data indicate that NAF is transported intracellularly in multiple oligomeric and conformational forms. PMID- 2324207 TI - Hydrophilic-interaction chromatography for the separation of peptides, nucleic acids and other polar compounds. AB - When a hydrophilic chromatography column is eluted with a hydrophobic (mostly organic) mobile phase, retention increases with hydrophilicity of solutes. The term hydrophilic-interaction chromatography is proposed for this variant of normal-phase chromatography. This mode of chromatography is of general utility. Mixtures of proteins, peptides, amino acids, oligonucleotides, and carbohydrates are all resolved, with selectivity complementary to those of other modes. Typically, the order of elution is the opposite of that obtained with reversed phase chromatography. A hydrophilic, neutral packing was developed for use in high-performance hydrophilic-interaction chromatography. Hydrophilic-interaction chromatography is particularly promising for such troublesome solutes as histones, membrane proteins, and phosphorylated amino acids and peptides. Hydrophilic-interaction chromatography fractionations resemble those obtained through partitioning mechanisms. The chromatography of DNA, in particular, resembles the partitioning observed with aqueous two-phase systems based on polyethylene glycol and dextran solutions. PMID- 2324208 TI - Analysis of glycoprotein-derived oligosaccharides by high-pH anion-exchange chromatography. AB - The technique of high-pH anion-exchange chromatography with pulsed amperometric detection has recently been shown to be a powerful method for resolving closely related oligosaccharides [M. R. Hardy and R. R. Townsend, Proc. Natl. Acad. Sci. U.S.A., 85 (1988) 3289-3293]. This report describes separations involving a total of nineteen different high-mannose, hybrid and complex-type oligosaccharides isolated after peptide: N-glycosidase F (PNGase F) or endo-beta-N acetylglucosaminidase H digestion of glycoproteins. Separations were carried out at a constant base concentration (0.1 M NaOH) using linear gradients from 0 to 0.2 M sodium acetate. The applicability of this chromatography for profiling the N-linked oligosaccharides of glycoproteins was demonstrated by generating "oligosaccharide maps" of PNGase F-liberated oligosaccharides from recombinant human tissue plasminogen activator, ribonuclease b, human transferrin, and bovine fetuin. Methods for recovering salt-free oligosaccharides after this chromatography were also investigated. On-line ion suppression with an anionic micromembrane suppressor cartridge was found to be capable of effective desalting up to a total sodium ion concentration of 0.15-0.2 M at a flow-rate of 1 ml/min. After high-pH anion-exchange chromatography with ion suppression, collected oligosaccharides were analyzed by fast-atom bombardment mass spectrometry after conversion to permethyl derivatives or after reductive amination with rho aminobenzoic acid ethyl ester. PMID- 2324209 TI - Automated evaluation of tryptic digest from recombinant human growth hormone using ultraviolet spectra and numeric peak information. AB - UV spectra were successfully employed in identifying peptide fragments from a tryptic digest of recombinant-DNA-derived human growth hormone (r-hGH). It was possible to distinguish very similar peptides utilizing a digital comparison of the UV spectra. An automated procedure was developed to generate a calibration library for the tryptic digest of a reference standard. The calibration library was then evaluated for reproducibility and selectivity and found to provide superior performance in correctly identifying ambiguous peaks as compared to the use of a conventional calibration table. Spectral match factors together with numerical information, derived from peak retention time, area and height, were used to arrive at a "peak score" descriptive of the similarity between standard and sample peaks. "Peak scores" could be combined to calculate a "sample score" indicative of overall similarity between an unknown and a standard. The scoring procedure was automated to generate a final report without operator intervention and successfully assigned appropriate scores to similar as well as dissimilar samples, e.g., native and oxidized r-hGH. PMID- 2324210 TI - Protein chromatography with pyridine- and alkyl-thioether-based agarose adsorbents. AB - In an attempt to identify the part of the ligand of 3-(2-pyridylthiol)-2 hydroxypropylagarose that is responsible for the specific adsorption of immunoglobulins and alpha 2-macroglobulin from serum, nine agarose derivatives were prepared: (I) 3-(N-2-iminopyridyl)-2-hydroxypropyl-, (II) 3-(4-pyridylthio) 2-hydroxypropyl-, (III) 3-(2-pyridylthio-N-oxide)-2-hydroxypropyl-, (IV) 3-(2 pyridylthio)-2-hydroxypropyl-, (V) 3-(ethylthio)-2-hydroxypropyl-, (VI) 3-(n butylthio)-2-hydroxypropyl-, (VII) 3-(2-aminoethylthio)-2-hydroxypropyl-, (VIII) 3-(2-hydroxyethylthiol)-2-hydroxypropyl- and (IX) 3-(N-2-pyridyl-2-one)-2 hydroxypropylagarose. The selective adsorption of the above serum proteins to these derivatives was analysed by chromatography. The electron distributions were calculated for three of the investigated pyridine derivatives in order to establish whether there is any relationship between the electron distribution in the molecule and the absorption properties of the pyridine derivatives. By optimizing the preparation methods for the different derivatives, the possible side-reactions were minimized and checked. The adsorbed serum proteins were determined by the Ouchterlony technique and electrophoresis. The concentration of human serum albumin in the different fractions was determined by conventional radioimmunological methods. These data make it possible to classify the adsorbents according to their selectivity and hydrophobic thiophilic behaviour. PMID- 2324211 TI - Estimation of the reversed-phase liquid chromatographic lipophilicity parameter log k'w using ET-30 solvatochromism. AB - The estimation of the reversed-phase liquid chromatographic lipophilicity parameter log k'w has been studied using the solvatochromic ET(30) polarity scale. Over 200 sets of chromatographic retention data were used to compare the log k'w estimates made from the volume percent of organic modifier (%) and ET(30) models of mobile phase strength. It was found that linear extrapolations of log k' versus ET(30) plots to the polarity of unmodified aqueous mobile phase gave a more reliable value of log k'w than linear regressions of log k' versus volume percent. This evaluation was based upon the relative value of the 95% confidence interval about log k'w, the point of intersection of log k' versus solvent strength plots for different modifiers, the scatter of estimations with different modifiers and the goodness-of-fit of the data to the linear model. Estimations of log k'w using the solvatochromic approach are found to give a more sensitive lipophilicity description than the volume percent approach. Recommended procedures for carrying out lipophilicity estimations with reversed-phase liquid chromatography are also discussed. PMID- 2324212 TI - Effect of alcohol chain length, concentration and polarity on separations in high performance liquid chromatography using bonded cyclodextrin columns. AB - The effect of alcohol chain length, concentration and polarity on separation in high-performance liquid chromatography using beta-cyclodextrin-bonded silica is discussed. The results show that retention times cannot be predicted merely from the polarity of the binary mobile phase. Although organic modifiers with the same physico-chemical properties and from the same solvent group were used, the retention times obtained using binary mobile phases having the same polarity, were different. It was also observed that normal-chain carbon alcohols gave retention times shorter than those obtained with a branched-chain alcohol (n propanol vs. isopropanol), and the longer the alcohol chain the shorter the retention times. A plot of ln k' vs. alcohol volume fraction for benzene, toluene, ethylbenzene, propylbenzene, butylbenzene, 1-phenylhexane and 1 phenyloctane gave a linear relationship in methanol, ethanol and propanol (except for 1-phenylhexane). A non-linear relationship was obtained for all the solutes in isopropanol, tert.-butanol and 1-butanol, in the alcohol volume fraction studied. PMID- 2324213 TI - Preparative-scale high-performance liquid chromatographic separation and purification of 3'-azido-3'-deoxythymidine-5'-phosphate. AB - Crude 3'-azido-3'-deoxythymidine-5'-phosphate (AZT-P), obtained from direct phosphorylation of 3'-azido-3'-deoxythymidine (azidothymidine, AZT), was separated and purified by isocratic preparative high-performance liquid chromatography. The components in a 2.5-g load of crude AZT-P, obtained from work up of the phosphorylation reaction, were separated in 50 min to give 1.8 g of 99.5% pure AZT-P. AZT-P was analyzed by high-performance liquid chromatography and by high-resolution nuclear magnetic resonance (1H, 13C, 31P) spectroscopy. The practical and rapid preparative chromatographic method is being applied to the purification of AZT-P and other antiretroviral dideoxynucleotides, used as intermediates in the synthesis of target-directed experimental drugs for the treatment of AIDS. PMID- 2324214 TI - Appraisal of four pre-column derivatization methods for the high-performance liquid chromatographic determination of free amino acids in biological materials. AB - Reversed-phase high-performance liquid chromatography (RP-HPLC) is a powerful method for assaying physiological amino acid concentrations in biological fluids. Four pre-column derivatization methods, with o-phthaldialdehyde (OPA), 9 fluorenylmethyl chloroformate (FMOC-Cl), phenyl isothiocyanate (PITC) and 1 dimethylaminonaphthalene-5-sulphonyl chloride (dansyl-Cl), were assessed with respect to their applicability in biological research. The methods permit the measurement of 21-26 major amino acids in 13-40 min. The superior sensitivity favours the use of OPA, FMOC-Cl and dansyl-Cl techniques. Because of instability of the OPA adducts, automated on-line derivatization is required when using this method in general practice. Application of the PITC method, although less sensitive, is useful in clinical chemistry, where sample availability is rarely a problem. Cystine determination is not feasible when using OPA or FMOC-Cl and with PITC the reproducibility and linearity are poor, whereas the dansyl-Cl method allows reliable quantitation. The four methods are currently used to perform ca. 8000 OPA and 5000-6000 FMOC-Cl, PITC and dansyl-Cl analyses of biological samples per year. The results obtained with the RP-HPLC methods compare favourably with those derived from conventional ion-exchange amino acid analyses. When the guard column is regularly changed after 120 analyses, the separation remains satisfactory for at least 700 OPA, 800 FMOC-Cl, 150 PITC and 500 dansyl-Cl analyses. Careful control of factors and limitations inherent in the various methodologies is a prerequesite for proper identification and appropriate quantitation. PMID- 2324215 TI - Preparation of electrophoric derivatives of N7-(2-hydroxyethyl)guanine, an ethylene oxide DNA adduct. AB - Ethylene oxide, a potential human carcinogen, mainly damages DNA by reacting at guanine sites to form N7-(2-hydroxyethyl)guanine. In order to determine this DNA adduct with high sensitivity by gas chromatography, we have prepared, for comparison purposes, four electrophoric derivatives. The two that are most promising to date are bis- and tris-pentafluorobenzyl products prepared by first chemically transforming the N7-(2-hydroxyethyl)guanine to a corresponding xanthine, and then reacting the latter with pentafluorobenzyl bromide. These two derivatives are obtained in good yields and give molar responses of 0.6 and 0.5, respectively, relative to that of lindane by gas chromatography with electron capture detection. PMID- 2324216 TI - Application of 3-(2-furoyl)quinoline-2-carbaldehyde as a fluorogenic reagent for the analysis of primary amines by liquid chromatography with laser-induced fluorescence detection. AB - 3-(2-Furoyl)quinoline-2-carbaldehyde (FQCA) has been synthesized and characterized as a fluorogenic derivatizing reagent for liquid chromatography. The reagent forms highly fluorescent isoindoles upon reaction with primary amines. The spectral properties and optimum reaction conditions for the formation of isoindoles have been investigated. The utility of FQCA for the high sensitivity analysis of amino acids by laser-induced fluorescence with an argon ion laser is demonstrated. PMID- 2324217 TI - Determination of fluoxetine and norfluoxetine by high-performance liquid chromatography. AB - A high-performance liquid chromatographic assay was developed for a recently introduced atypical antidepressant, fluoxetine and its demethylated metabolite, norfluoxetine. Prior to analysis, aliquots of alkalinized plasma were extracted with n-hexane and isoamyl alcohol, followed by back-extraction with diluted phosphoric acid. These extracts were injected into a 10 microns, reversed-phase C18 column with phosphate and acetonitrile as the mobile phase and detection at 214 nm. Peak height ratios were linearly correlated up to 800 micrograms/l. Acceptable coefficients of variation were demonstrated for both within-run and day-to-day studies. Selected drugs were checked for interference. The assay was used to monitor nine patients receiving 20 to 80 mg of fluoxetine per day. Plasma concentrations of fluoxetine and norfluoxetine ranged from 37 to 301 micrograms/l and 29 to 326 micrograms/l respectively. PMID- 2324218 TI - On-line high-performance liquid chromatography for the determination of cephalosporin C and by-products in complex fermentation broths. AB - A fully automated high-performance liquid chromatographic system was developed for optimization of cephalosporin C production. Using a simple, isocratic, reversed-phase method, cephalosporin C, deacetylcephalosporin C, deacetoxycephalosporin C, penicillin N, methionine and its decomposition product 2-hydroxy-4-methylmercaptobutyric acid were determined. The method worked reliably for 250 h and supplied information on the influence of many parameters of the process. PMID- 2324219 TI - Separation of carotenes on cyclodextrin-bonded phases. AB - The separation of carotenoids and retinoids on a beta-cyclodextrin-bonded stationary phase with conventional mobile phases is reported. Compounds studied include beta-carotene (all-trans), 15,15'-cis-beta-carotene, 7,8,7',8'-dihydro beta-carotene, alpha-carotene, lycopene, lutein, zeaxanthin, retinal, retinol, retinol palmitate and retinol acetate. The best resolution of carotenes was obtained with low concentrations (less than or equal to 1%) of polar solvents (e.g., 2-propanol or ethyl acetate) in hexane or cyclohexane. Xanthophylls required much higher concentrations of polar solvents. The best solvent for the resolution of lutein and zeaxanthin was found to be dichloromethane. The resolution of cis/trans-isomers and the tentative identification of other isomers present in newly synthesized carotenoid standards is also reported. All-trans isomers were found to be eluted before cis-isomers. PMID- 2324220 TI - Thermodynamic model for electrostatic-interaction chromatography of proteins. AB - A thermodynamic model derived by Record et al. [M. T. Record, Jr., Biopolymers, 14 (1975) 2137 and M. T. Record, Jr., C. F. Anderson and T. M. Lohman, Q. Rev. Biophys., 11 (1978) 103] from Wyman's linkage theory [J. Wyman, Adv. Protein Chem., 19 (1964) 223] using Manning's condensation model [J. Manning, J. Chem. Phys., 51 (1969) 924] was extended to electrostatic interaction chromatography. Mixed, electrostatic and hydrophobic interactions of a model protein, ovalbumin were characterized by ion and water release. PMID- 2324221 TI - Calculation of column performance in nitrate removal from water supplies by anion exchange. PMID- 2324222 TI - Capillary electrophoresis with indirect amperometric detection. AB - The use of indirect amperometric detection with capillary electrophoresis is demonstrated. The system consists of a porous glass coupler which allows amperometric detection at a carbon fiber electrode placed in the end of the capillary. 3,4-Dihydroxybenzylamine is added to the buffer system as a continuously eluting electrophore. Indirect amperometric detection in 9-mumol I.D. capillaries provides detection limits as low as 380 attomole for the amino acid arginine. Finally, both direct and indirect amperometric detection can be accomplished simultaneously. PMID- 2324223 TI - Physicochemical studies of biologically active peptides by low-temperature reversed-phase high-performance liquid chromatography. AB - The high-performance liquid chromatographic separation of biologically active peptides containing 1-prolyl residues is demonstrated. Rapid isomer interconversion between cis- and trans-isomeric forms at the prolyl peptide bond is shown to produce classical secondary equilibrium effects in the peak shapes. By operating the column at temperatures in the range -15 degrees C to 5 degrees C it is possible to obtain normal separations of the various isomeric forms. The use of low column temperatures makes physicochemical studies possible, e.g., the effect of pH on isomer composition in free solution as reported here for morphiceptin. PMID- 2324224 TI - Reversed-phase chromatographic behavior of proteins in different unfolded states. AB - A series of standard small globular proteins in different unfolded states was studied by gradient reversed-phase liquid chromatography. The retention parameters Z [slope of log capacity factor (k') vs. log molar concentration of organic modifier, 1-propanol, in the mobile phase] and log I (the value of log k' at 1 M 1-propanol) were derived from gradient retention data. Each protein in four different conformational states, i.e., folded, chromatographic surface unfolded, urea-unfolded and disulfide-bridge reduced-unfolded, showed a variation of 10-fold in Z and up to 10(12)-fold in I values. For the different states of all the proteins studied, the order of Z and I values was as follows: folded much less than surface-unfolded less than urea-unfolded less than reduced-unfolded. The differences in the values of the coefficients suggest, in agreement with literature reports, that proteins with their disulfide bridges cleaved have the largest degree of unfolding. In addition, the Z and I values and solution refolding kinetics all suggest that chromatographic surface-unfolded proteins have a lower degree of unfolding than their urea-unfolded forms. It was also found that an additional chemical cross-link in lysozyme caused a significant decrease in the first-order rate constant of the surface-induced unfolding process. PMID- 2324225 TI - Isoelectric focusing studies of concanavalin A and the lentil lectin. AB - Isoelectric focusing (IEF) of metallized and demetallized preparations of concanavalin A (Con A) consisting of either intact or fragmented subunits shows different band patterns. Metallized Con A consisting of intact polypeptide chains (intact Con A) has an isoelectric point (pI) 8.35. Metallized preparations consisting of fragmented chains (fragmented Con A) show three bands with pI values 8.0, 7.8 and 7.7. Demetallized intact Con A (intact apoCon A) has a pI of 6.5, however, it undergoes pH dependent association during IEF under certain conditions, which gives rise to multiple bands. Ampholyte-mediated demetallization of intact and fragmented Con A and subsequent aggregation of the apoprotein results in multiple bands during IEF in the presence of the pH range 3 to 10 ampholytes. However, ampholytes of the pH range 7 to 9 do not demetallize the proteins and show a single band with intact Con A. The pI of intact Con A remains essentially the same in the presence of inhibitory sugar. Furthermore, different moleculars forms of Con A, including locked and unlocked conformers of intact apoCon A, and the dimeric and tetramic states of both intact Con A and intact apoCon A have been identified and their pI values determined. IEF of the lentil isoelectins, LcH-A and LcH-B, shows single bands of pI 8.5 and 9.0, respectively. However, the native lectin mixture gives rise to an additional band of pI 8.8 due to a hybrid protein formed by ampholyte-mediated subunit exchange between the isolectins. PMID- 2324226 TI - Determination of biopolymer (protein) molecular weights by gradient elution, reversed-phase high-performance liquid chromatography with low-angle laser light scattering detection. AB - The determination of molecular weights for certain proteins has been performed. This has involved the on-line coupling of gradient elution, reversed-phase high performance liquid chromatography (RP-HPLC) with low-angle laser light scattering (LALLS) detection. A new 1.5-micron, non-porous, Monosphere RP-C8 column has been used in order to perform fast and conventional RP-HPLC gradients (5-45 min). Traditional specific refractive index increment (dn/dc) and refractive index (n) measurements have been performed in order to derive absolute weight-average molecular weight (Mw) information for ribonuclease A, lysozyme, and bovine serum albumin. Standard mixtures of known concentrations of each protein have been separated using reversed-phase gradients utilizing acetonitrile with on-line LALLS determination of excess Rayleigh scattering factors. Accurate Mw data have been obtained for all three proteins, but only under certain, conventional reversed-phase gradient elution conditions. Between 5-10 min of fast gradient elution, each protein appears to exhibit unusual Mw values, suggestive of aggregate formations. Methods have been developed to define the nature of such aggregates. The on-line coupling of modern RP-HPLC for biopolymers with LALLS represents a major step forward in the ability of bioanalytical chemists to determine the nature (monomer versus aggregate) of such materials. Other classes of biopolymers should prove suitable for studies with the same RP-HPLC-LALLS-UV approaches. PMID- 2324227 TI - Purification of histone H1 polypeptides by high-performance cation-exchange chromatography. AB - Calf thymus histone 1 (H1) was cleaved by chemical and enzymatic methods and the resulting polypeptides were fractionated by high-performance cation-exchange. Up to 1 mg of H1 polypeptides were loaded onto a 50 x 5 mm I.D. cation-exchange column and fractionated to greater than 95% purity in less than 30 min. This is the first report on the separation of H1 polypeptides by a strong cation-exchange matrix. In addition, the high-performance cation-exchange chromatography protocol represents a significant decrease in fractionation time when compared to conventional ion-exchange and gel filtration chromatography. The utility of this procedure is shown when the H1 peptides purified by the protocol were used to define antigenic domains of H1 band by procainamide-induced lupus and idiopathic systemic lupus erythematosus. The majority of the sera tested by enzyme-linked immunoassay (ELISA) reacted to the C-terminal peptides of H1 indicating this to be the major antigenic domain of H1. PMID- 2324228 TI - Method for the isolation and liquid chromatographic determination of eight sulfonamides in milk. AB - A method for the isolation and liquid chromatographic determination of eight sulfonamides in milk is presented. Fortified or blank milk samples (0.5 ml) were blended with octadecylsilyl (C18T) derivatized silica (2 g). A column made from the sample C18T matrix was first washed with hexane (8 ml) following which the sulfonamides were eluted with methylene chloride (8 ml). The eluate contained sulfonamide analytes which were free from interferences when analyzed by high performance liquid chromatography (HPLC) utilizing UV detection (270 nm, photodiode array). Standard curve correlation coefficients (range, 0.998 +/- 0.002 to 0.999 +/- 0.001), average percentage recoveries (73.1 +/- 7.4 to 93.7 +/ 2.7%), and the inter-(3.9-9.6%) and intra-assay (2.2-6.7%) variabilities, were determined for the concentration range examined (62.5-2000 ng/ml) and resulted in a minimal detectable limit of 1.25 ng on column (62.5 ng/ml, 20 microliters injection from a final sample volume of 0.5 ml). Savings in terms of time and solvent make this procedure attractive when compared to classical isolation techniques for sulfonamides. PMID- 2324229 TI - Using standards in practice. PMID- 2324230 TI - Development and use of the ANA standards of gerontological nursing practice. PMID- 2324231 TI - Implementing the ANA/ONS Standards of Oncology Nursing Practice. PMID- 2324232 TI - Using the ANA standards as a basis for performance evaluation in the home health care setting. PMID- 2324233 TI - Clinical nursing standards: toward a synthesis. PMID- 2324234 TI - A survey of the utilization of the ANA's standards of practice in Wisconsin. PMID- 2324235 TI - Using standards for obstetrical nursing QA. PMID- 2324236 TI - Using research to identify why nurses do not meet established sexuality nursing care standards. PMID- 2324237 TI - Planned and systemic QA process to assure continual improvement in thrombolytic therapy administration. PMID- 2324238 TI - Comparison of fortified calf serum, serum substitutes and fetal calf serum with or without extenders for propagation of cell cultures for virus plaque assays. AB - Two studies comparing sewage-isolated and laboratory stock viruses were conducted to determine if alternative forms of serum or serum extenders could be used in place of fetal bovine serum without a significant loss of viral titer. In the first study, BGM cells were grown in standard MEM-L15 medium which was supplemented with Nuserum, Sigma serum replacement (CPSR-1), HyClone defined iron supplemented calf bovine serum, fetal bovine serum (FBS) or FBS supplemented with either SerXtend or Mito serum extenders. Comparison of virus titers showed that CPSR-1 gave the best overall results and was comparable to FBS. Of the serum extenders, only SerXtend improved virus recovery from sewage samples. In the second study, all sera were tested with and without SerXtend. In these experiments, SerXtend enhanced virus sensitivity of the BGM cell line grown in the HyClone serum but reduced the sensitivity of those cultured in Sigma serum. In both series, the growth of BGM cells was monitored for 12 weeks and all test products were shown to support long-term cell growth. PMID- 2324239 TI - Non-invasive measurement of pyruvate and glucose uptake and lactate production by single human preimplantation embryos. AB - The consumption of pyruvate and glucose and the production of lactate by 40 single human preimplantation embryos has been measured using a non-invasive technique. Twelve of the embryos showed abnormal fertilization. Of the 28 normally fertilized embryos, nine (32%) developed to the blastocyst stage in culture while the remainder degenerated or arrested during cleavage. In the normal embryos, pyruvate uptake exceeded that of glucose in the early developmental stages (days 2-5 post-insemination) before glucose became the predominant substrate in the blastocyst (day 6). Considerable quantities of lactate were formed throughout development, rising from a value of 43.6 pmol/embryo/h on day 2.5 to 95.4 pmol/embryo/h on day 5.5. The values of pyruvate and glucose uptake and lactate production of those embryos which arrested were below those which developed normally. On the basis that one mole of glucose can give rise to two moles of lactate, only 50% of the lactate produced could be accounted for in terms of glucose uptake from the medium. This figure rose to 90% in the blastocyst. The remaining lactate must be derived from endogenous sources, most probably glycogen. It is proposed that the high production of lactate by human preimplantation embryos in vitro is an adaptation to the conditions of culture. PMID- 2324240 TI - Observations on the morphology of pronuclei and nucleoli in human zygotes and implications for cryopreservation. AB - The effects of cryopreservation on human zygotes at various stages between the appearance of pronuclei and their close association were investigated. Pronuclear zygotes (n = 233) from 101 patients were frozen using propanediol 21-35 h following egg collection. The incidence of implantation of thawed pronuclear zygotes frozen 29-35 h following oocyte collection was significantly higher than that of younger pronuclear zygotes (28 versus 10%, respectively). Zygote age did not affect cell survival following cryostorage. The diameter and association of pronuclei and the number and distribution of nucleoli were determined from video tape recordings of 140 fresh zygotes. Pronuclear migration continued after pronuclear enlargement. The number of nucleoli remained constant during pronuclear migration, but their random distribution within the pronucleus diminished. Strongly adhered pronuclei had significantly more aligned nucleoli on adjacent sides than pronuclei which were still visually separated by ooplasm. This equatorial distribution of nucleoli was noted in the majority of zygotes older than 26 h. The findings suggest that zygote cryopreservation should be initiated when pronuclear migration is completed. This moment can be determined accurately by studying pronuclear association and nucleolar alignment. PMID- 2324241 TI - Serum levels of CA 125 during the first trimester of normal outcome, ectopic and anembryonic pregnancies. AB - Single serum samples were obtained during the first trimester of pregnancies with a retrospectively normal outcome (n = 150), ectopic pregnancies (n = 38) and anembryonic pregnancies (n = 78). Serial samples during the first trimester were also obtained from 43 women achieving pregnancy following successful treatment for infertility and with a retrospectively defined normal outcome. Significant variation in serum CA 125 levels in relation to gestational age was observed in pregnancies with a normal outcome (P less than 0.0001). Peak serum CA 125 levels were observed at 6-7 weeks, the mean level at this gestation being 40.1 U/ml (range 31.7-50.7 U/ml) in the normal conception/normal outcome group and 36.5 U/ml (range 25.6-52.0 U/ml) in the assisted conception/normal outcome group. A rise and fall in serum CA 125 levels during the first trimester was observed in 42 of 43 assisted conceptions monitored serially, with peak levels ranging from 7 to 1398 U/ml (median 48.8 U/ml) occurring at 28-61 days (median 45 days) gestation. Mean serum CA 125 levels were higher in the anembryonic pregnancy group at 4-5 and 6-7 weeks gestation than in both normal pregnancy outcome groups (P less than 0.01). PMID- 2324242 TI - Adrenoceptors mediating contraction in the human uterine artery. AB - Pharmacological characterization of adrenoceptors mediating smooth muscle contraction was performed in isolated preparations from the human uterine artery. The mixed alpha 1- and alpha 2-adrenergic agonist, noradrenaline (NA) and the selective alpha 1-agonists, phenylephrine and methoxamine, all contracted the smooth muscle preparations in a concentration-dependent manner. The responses were antagonized competitively by the selective alpha 1-antagonist, prazosin, yielding pA2 values for the three agonists (8.33-9.08) typical for an interaction with alpha 1-receptors. The alpha 2-selective receptor agonists, clonidine and BHT 920, did not exert any contractile effects in the isolated uterine arteries, and the alpha 2-adrenergic antagonist, yohimbine, counteracted the contractile effect of NA only at high concentrations. The concentration-response curve for NA was unaffected by the alpha 2-selective antagonists, rauwolscine and idazoxan. The results suggest that the postjunctional contractile receptors in the human uterine artery primarily are of the alpha 1 type, and give no evidence for any substantial involvement of alpha 2-receptors in this important tributary vessel of the human female reproductive tract. PMID- 2324243 TI - The early luteal phase in successful and unsuccessful implantation after IVF-ET. AB - The hormonal milieu at embryo implantation after in-vitro fertilization was investigated. Superstimulation was accomplished with clomiphene citrate and human menopausal gonadotrophin (HMG) injections followed by ovulation induction with human chorionic gonadotrophin (HCG). Venous blood samples were drawn on days 2 and 8, the day of oocyte recovery being day 0. Fifteen women with successful implantation, defined as an ultrasound-verified pregnancy, were compared to 42 women with unsuccessful implantation, using a three-way analysis of variance. Oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) did not differ between the two groups. However, the ratios of oestradiol/progesterone and of testosterone/SHBG were significantly higher in the non-fertile cycles, both on day 2 and on day 8 (P less than 0.05). Furthermore, there was a highly significant decrease in oestradiol, progesterone and testosterone between days 2 and 8 in fertile as well as in non-fertile cycles (P less than 0.001) and a highly significant increase in SHBG from day 2 to day 8 in both groups (P less than 0.001). The higher testosterone/SHBG ratio in the non pregnant women implies a relative hyperandrogenicity in this group that might have adversely affected the uterine receptivity. PMID- 2324244 TI - In-vitro fertilization: influence of women's age on pregnancy rates. AB - An analysis of the influence of women's age on the results of in-vitro fertilization was performed, using 5590 attempts collected during the year 1986. Increasing age was found to be related to decreased success rates from 19.8% per attempt below the age of 25 years, to 9% per attempt at 40 years or more. A cut off point was found between the ages of 36 and 37 years, using a mathematical model. The decrease was related to a reduction in oocyte production (4.3 +/- 2.8 at 25 years or less and 3.3 +/- 2.1 at 40 years or more, P less than 0.001), and to a reduced implantation rate, whatever the number of transferred embryos. These findings were not due to spouse's age, rank of attempt, infertility diagnosis or oocyte stimulation regimen, since the effect of age remained significant when a logistical model including these confounders was applied. Finally, a woman's age must be considered as a prognostic factor when IVF is proposed to infertile couples. PMID- 2324245 TI - Ultrastructure of the cortex in the human egg. AB - Two distinct types of cortical granules were discerned in the human oocyte. The first type, G1 granules, had a mean diameter of 350 nm, contained a uniformly compacted, electron-dense substance; these granules were probably synthesized even before the oocyte was aspirated from mature follicles and their contents were never found to be secreted in any of the preovulatory (immature), unfertilized and fertilized eggs examined. The G2 granules measured 450 nm (mean diameter), had a granular content and were found to be synthesized and secreted at all the stages of egg development studied. Endocytosis was also evident in the unfertilized and fertilized eggs. The secretion of the G1 cortical granules even before fertilization suggests that they may have an additional role, rather than merely contributing to the blockade of polyspermy. PMID- 2324246 TI - Impairment of the hatching process following IVF in the human and improvement of implantation by assisting hatching using micromanipulation. PMID- 2324247 TI - Variation in the cholesterol/phospholipid ratio in human spermatozoa and its relationship with capacitation. AB - The cholesterol/phospholipid (C/PL) ratio was determined for spermatozoa from eight men with normal semen parameters. There was a close correlation between the C/PL ratio and the rate of sperm capacitation as assessed by the hamster egg penetration test. A lower C/PL ratio correlated with a faster capacitation time. This supports the notion that the loss or reduction of membrane cholesterol constitutes an important step of capacitation in human spermatozoa. PMID- 2324249 TI - Differential evaluation of human sperm hypoosmotic swelling test and its relationship with the outcome of in-vitro fertilization of human oocytes. AB - The hypoosmotic swelling test is a simple laboratory test to measure the functional integrity of the human sperm membrane. Its in-vivo and in-vitro applicability needs to be evaluated before it can be accepted as a useful routine test for the fertilizing potential of human semen. We studied the standard semen analysis results and differential sperm tail swelling patterns of seminal and swim-up sperm after hypoosmotic treatment in 97 semen samples used for in-vitro fertilization of human oocytes. Semen samples were classified as infertile (0% fertilization rate; n = 27) or fertile (greater than 0% fertilization rate; n = 70) before statistical analyses. There was a significant difference (P less than 0.005) in percentage normal morphology of seminal sperm between the fertile and infertile semen samples. The percentage normal morphology of seminal sperm correlated (r = 0.4250; P less than 0.005) with the in-vitro fertilization rate of human oocytes and this parameter was selected by the multivariate stepwise discriminant analysis as the discriminator capable of predicting the in-vitro fertilization rate with 57.7% accuracy. The percentage total swelling of seminal and swim-up sperm after hypoosmotic treatment was not correlated with the in vitro fertilization rate. The percentage swelling pattern g (the open type) of seminal sperm was also selected by the multivariate stepwise discriminant analysis as the discriminator to predict the in-vitro fertilization rate. This parameter correlated with the percentage normal morphology of seminal sperm (r = 0.3014; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324248 TI - Comparison between different pre-treatment techniques for sperm recovery prior to intrauterine insemination, GIFT or IVF. AB - An attempt was made to compare different pre-treatment techniques in 16 normal and proven fertile and 30 subnormal and hitherto infertile semen samples. The techniques used were (i) standard, (ii) layering, (iii) discontinuous Percoll density gradient and (iv) albumin columns. Percoll gradient was most effective in separating a high fraction of progressive motile spermatozoa (75 and 57% in normal and subnormal semen samples, respectively). The albumin columns, as well as the standard techniques, were equally effective in recovering 45 and 24% respectively of progressive motile spermatozoa in normal and subnormal semen samples. The layering method was the least effective of the four techniques (4% recovery in normal and subnormal semen samples). In cases of contamination with inflammatory cells, the standard and layering methods were significantly (P less than 0.001) more advantageous than isolations with Percoll gradient and albumin columns. The percentage of ideal forms of spermatozoa recovered from a normal semen sample was significantly higher with the standard (P less than 0.01), layering (P less than 0.05) and Percoll gradient (P less than 0.05) techniques. In subnormal samples, only the Percoll gradient gave a significantly (P less than 0.02) higher percentage of ideal forms, whereas the other techniques were less effective. The significance and practical use of the various pre-treatment techniques are discussed in relation to the characteristics of the pre-treatment semen sample. PMID- 2324250 TI - Quantitative evaluation of spermatogenesis by testicular histology in men with congenital absence of the vas deferens undergoing epididymal sperm aspiration. AB - A quantitative histological evaluation of testicular biopsy in patients undergoing microsurgical epididymal sperm retrieval for in-vitro fertilization revealed no correlation between the quantity or quality of spermatozoa retrieved and the actual testicular sperm production. Poor retrieval of sperm was associated with blockage induced by secondary pressure damage in the rete testis collecting area. PMID- 2324251 TI - Ionized calcium in human male and female reproductive fluids: relationships to sperm motility. AB - The levels of ionized calcium in seminal plasma were approximately 20% of the serum levels. In contrast, cervical mucus contained a level of ionized calcium similar to both serum and follicular fluid. Titration of seminal plasma and serum with increasing concentrations of calcium chloride indicated a 10-fold higher calcium-binding capacity for seminal plasma. In a random group of men under semen investigation, concentrations of ionized calcium and citrate in semen were inversely correlated (r = 0.732; P less than 0.001), an observation which was confirmed by studies of split ejaculates. These findings supported the contention that citrate is the major regulator of the levels of ionized calcium in seminal plasma and primarily responsible for maintaining the calcium gradient between the seminal plasma and cervical mucus. No significant relationship could be demonstrated between the levels of ionized calcium in the ejaculates and any of the motility characteristics of the spermatozoa in the same sample. Furthermore, the addition of increasing quantities of calcium chloride (0.16-20.00 mM) to washed spermatozoa had no major effects on their progressive motility. These data suggest that human spermatozoa are effective in maintaining an appropriate level of internal ionized calcium, necessary for normal motility, despite fluctuations in external calcium. PMID- 2324252 TI - Immunohistological distribution of the secretory endometrial protein, 'pregnancy associated endometrial alpha 2-globulin', a glycosylated beta-lactoglobulin homologue, in the human fetus and adult employing monoclonal antibodies. AB - We have previously demonstrated that pregnancy-associated endometrial alpha 2 globulin (alpha 2-PEG), the human glycosylated beta-lactoglobulin homologue (HG BLG), is quantitatively the major secretory soluble protein product of the secretory endometrium during the latter half of the menstrual cycle and decidua spongiosa of the gestational endometrium during early pregnancy, and is principally localized to the glandular epithelium. In the present study employing monoclonal antibodies in immunohistological techniques, the distribution and localization has been examined in normal and pathological tissues of the adult and first-trimester fetus. No significant staining for alpha 2-PEG was detected in any non-reproduction-associated tissue in the normal adult nor any tissue in the fetus. In the adult, most intense staining was associated with the endometrial glandular epithelium in the uterus or in ectopic sites in patients with endometriosis. During the menstrual cycle and pregnancy, appearance of alpha 2-PEG in endometriosis was strongly linked with its appearance in uterine endometrial tissue, suggesting that endometriotic tissue exhibited competence to respond to the same hormonal milieu required to induce synthesis in the uterine endometrium. Localization to the mucosal epithelium of the Fallopian tube was consistent with synthesis of alpha 2-PEG, albeit at low levels, and staining at this site reflected fluctuations of staining within the uterus. Of the pathological specimens examined, staining was only detected in a proportion of ovarian carcinomas. No staining was detected in the mammary gland, a site of beta lactoglobulin synthesis, whether obtained during pregnancy or lactation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324253 TI - Restitution of fertility in sterilized mice by transferring primordial ovarian follicles. AB - Primordial follicles isolated from infant mouse ovaries by enzymatic disaggregation have been transferred to the ovaries of sterile adults. They were transferred after being recombined and incubated in a plasma clot which was inserted either into ovaries which had been sterilized by X-irradiation or into vacant periovarian capsules immediately after ovariectomy. Irrespective of the type of operation, these grafts underwent morphogenesis to form replicas of the normal ovary, which were generally indistinguishable in respect of form, histological appearance and function. The numbers of follicles in these so-called transgerminative ovaries were highly variable, but all stages of follicular maturation up to Graafian stage were represented in most of them, while grafts that had been X-irradiated before transfer were sterile. Ovaries forming from fertile grafts were capable of spontaneous ovulation and the majority of animals carrying them were sexually receptive to males. Mating often resulted in pregnancies and those delivering at full-term produced normal offspring. PMID- 2324254 TI - Autoradiographic localization of [3H]RU 486 and [3H]progesterone in the uterus, pituitary and hypothalamus of the rat. AB - Twenty-one castrated oestrogen-primed Wistar rats, which were 2-months-old, were injected via the jugular vein with 100 microCi/100 g body weight of [3H]RU 486 or [3H]progesterone. Some of these received unlabelled compounds for competition studies. Samples of reproductive tract, pituitary and hypothalamus were excised after 15 min. The 4-micron frozen sections were processed for thaw-mounted autoradiography. The exposure time of the autoradiogram was approximately 6 months. After the injection of [3H]RU 486 and [3H]progesterone, the nuclear concentration of radioactivity was most distinct in muscular and stromal cells of the uterus, and the epithelial nuclei of lumina and glands showed weak labelling. Nuclear localization was also observed in muscle cells of the vagina, cervix and oviduct. After injection of [3H]progesterone, the radioactivity was found in the nuclei and cytoplasm of anterior pituitary cells and some cells showed a preferential nuclear concentration of radioactivity. The distribution of [3H]RU 486 in the anterior pituitary was more extensive than that of [3H]progesterone. In the hypothalamus, specific localization of [3H]RU 486 and [3H]progesterone existed in neurones accumulated in the preoptic nucleus, preoptic suprachiasmatic nucleus and the periventricular nucleus. No localization was found in the diaphragm. Pretreatment with RU 486, but not with dexamethasone, reduced the nuclear concentration of radioactivity of [3H]progesterone in the vagina, uterus, oviduct, pituitary and hypothalamus. The nuclear concentration of radioactivity after injection of [3H]RU 486 was also decreased by preinjection with progesterone. The autoradiographic results suggest that RU 486 and progesterone competed for the specific binding site (possibly a progesterone receptor) in the target cells at the levels of the uterus, pituitary and hypothalamus in vivo. PMID- 2324255 TI - Endometrial assessment in a group of infertile women on stimulated cycles for IVF: immunohistochemical findings. AB - An immunohistochemical assessment of the endometrium was carried out in a group of IVF patients on stimulated cycles, in order to evaluate this technique against standard histological methods and to consider its application in a clinical situation. Monoclonal antibodies to the two cycle-dependent proteins: pregnancy associated endometrial alpha 2-globulin (alpha 2-PEG) and 24K (a protein originally isolated from an oestrogen-dependent breast tumour line, MCF-7) were used in the experiment. Immunohistochemical results concerning the effect of drug stimulation, age and date of biopsy on the secretory state of the endometrium revealed trends which were consistent with previous histological data, helping to confirm the value of this new technique. In addition, several specimens were found to have a normal, i.e. in phase, histological appearance but to have an atypical pattern of protein secretion. These observations suggest that biochemical monitoring of the uterus should be used in conjunction with routine histological dating. PMID- 2324256 TI - Early or late monitoring of stimulation of ovulation for in-vitro fertilization? A methodological discussion of a randomized study. AB - Two GnRH agonist long-stimulation protocols, in association with HMG, are compared on a random basis. Group A (n = 53) was monitored daily from the 6th day of stimulation, whereas monitoring in group B (n = 55) began on the 11th day of stimulation. There was no significant difference in the numbers of follicles which matured, the numbers of collected oocytes, the numbers of embryos obtained in vitro and the clinical pregnancy rate. But the power of such a study is very weak (6%). It would have been necessary to include greater than 1000 patients in each group to obtain a bioequivalence test. Such a study is unrealistic for a single centre and multicentric studies are very difficult to achieve because of practical difficulties. A pooled analysis is perhaps the methodological answer. PMID- 2324257 TI - Seminal plasma anti-sperm antibodies and IVF: the effect of semen sample collection into 50% serum. AB - A retrospective analysis was carried out which studied IVF results for couples in whom the male partner had anti-sperm antibodies in seminal plasma, as judged by a positive MAR test. Of the 59 couples studied over a total of 113 cycles, 30 had IVF semen samples collected into sterile, dry pots. Thirty-eight of the couples had samples collected into medium containing 50% serum, and nine couples underwent separate treatment cycles with samples collected both dry and into 50% serum. The results demonstrate that the addition of serum to sample collection pots significantly improves the oocyte fertilization rate and is followed by a greater chance of conception for these couples. PMID- 2324259 TI - Post-operative artificial insemination--does it improve GIFT outcome? AB - Based on a retrospective study of our gamete intra-Fallopian transfer (GIFT) programme we have analysed 102 cycles where a standard GIFT procedure was implemented and 92 cycles where a post-operative intrauterine and intracervical insemination (post-operative IUI/ICI) was performed, in addition to GIFT. Our comparison suggests that the pregnancy outcome has been significantly improved (P less than 0.05) by this additional post-operative IUI/ICI. The standard GIFT group (102 cycles) yielded 38 clinical pregnancies and, ultimately, 29 delivered pregnancies (37.2/28.4%), whilst the post-operative IUI/ICI group (92 cycles) gave 48 clinical pregnancies initially and, currently, 38 pregnancies are ongoing or delivered (52.2/41.3%). The possible implications of the 'normal' presence of spermatozoa in the human female tract as an explanation for this improvement is discussed, and the adoption of IUI/ICI after GIFT is proposed, following a prospective controlled study. PMID- 2324258 TI - Retrograde tubal transfer of human embryos. AB - This preliminary study was designed to evaluate retrograde cannulation of the Fallopian tubes up to the isthmo-interstitial junction using the new technique of tubal embryo stage transfer (TEST). Follicular aspiration was performed under the guidance of a vaginal ultrasound probe in 51 women treated with GnRH + HMG. The oocytes retrieved were inseminated in vitro with 50,000 motile spermatozoa and kept in Menezo B2 medium without serum, at 37 degrees C, in an atmosphere of air + 5% CO2. The eggs were checked 24 and 36 h after insemination. No fertilization occurred in 23 patients. Cleaved embryos were obtained in the 28 other patients. One to seven embryos at the 2-4-cell stage were transferred with the 'Baudelocque Black Catheter' (BBC) into one tube and spare embryos were frozen. Five pregnancies occurred after retrograde TEST, for a pregnancy rate of 9.8% per cycle and 17.9% per transfer. One patient has given birth to a normal full-term baby. One singleton and one twin pregnancy are ongoing (8 months in June 1989). The other two pregnancies were ectopic. PMID- 2324260 TI - Automated semen analysis shows an increase in sperm concentration and motility with time in Makler chambers having excess sample volume. AB - The sperm concentration and motility within a Makler chamber increased markedly after 3-5 min of settling when one large drop (approximately 24 microliters) of semen was loaded in the chamber. The values remained stable when a 5-microliter volume was loaded and were intermediate with a 10-microliter volume. In order to obtain accurate data, it is necessary to load the Makler chamber with a semen volume of no more than 5 microliters. PMID- 2324261 TI - Cytogenetic analysis of biopsied preimplantation mouse embryos: implications for prenatal diagnosis. AB - Genetic diagnosis of enzyme deficiencies have been developed in mouse models using biopsied preimplantation embryos. A technique for preimplantation cytogenetic analysis was developed using embryos which were biopsied at the 4 cell, 8-cell and morula stage. Three culture methods were compared, using exposure directly to colchicine or preculture or overnight culture with subsequent exposure to colchicine. Some biopsies were lost through cell death (4.7-20.3%) and technical problems (11.1-27.8%), whilst others remained in interphase (13.0-46.5%). Air-dried preparations were successfully G-banded and karyotyped by modifying routine banding procedures. Biopsies placed directly into colchicine yielded the greatest mitotic index. However, chromosome morphology was unsuitable for G-banded analysis. After a short preculture, 71.4% of fixed 8-cell biopsies were karyotyped. The success of analysis of 8-cell biopsies is probably partly related to the higher mitotic index of intact embryos at this stage. Loss of chromosomes through scatter and chromosome overlapping limited analysis, particularly in biopsies with only one metaphase. The present success rate is not acceptable for the application of this technique to human prenatal diagnosis. However, it presents a useful tool for the study of chromosomal error at the research level. PMID- 2324262 TI - Assessment of the viability and pregnancy potential of mouse embryos biopsied at different preimplantation stages of development. AB - The developmental potential in vitro and in vivo of preimplantation mouse embryos biopsied at the 4-cell, 8-cell and morula stages were investigated. Biopsy had the least impact when performed at the 8-cell stage. There was no effect of biopsy on the development of 8-cells of blastocysts in vitro (95% compared with 99% of controls) or the implantation rate after transfers (82 versus 87%, P greater than 0.05); however, fewer embryos (52 versus 71%, P less than 0.05) resulted in viable fetuses. There was no effect of biopsy at the 8-cell stage on fetal weight on day 17. Blastocyst formation in vitro was significantly less for 4-cell biopsies compared with their controls (76 versus 90%, P less than 0.001) and biopsy also affected the implantation rate (44 versus 59%, P less than 0.01). Biopsy was most detrimental when performed on morulae, reducing the implantation rate from 65% for controls to 21% for biopsies (P less than 0.001). Fetal viability was also markedly affected with a reduction on day 17 from 42 to 26% accompanied by a significant reduction (24%, P = 0.02) of the mean fetal weight. Handling of embryos for biopsy at the morula stage, which involved removal of the zona pellucida, was a significant but not complete cause of the reduced implantation potential observed (sham-controls and intact-controls: 34 and 65%, P less than 0.001), while puncture of the zona during the biopsy of 4-cell and 8 cell embryos had no effect. Therefore, the 8-cell mouse embryo is the most suitable state for embryo biopsy. PMID- 2324263 TI - Micro-centrifugation of human spermatozoa: its effect on fertilization of hamster oocytes after micro-insemination spermatozoal transfer. AB - Micro-centrifugation (MC) at 6500 r.p.m. (3352 g) has not been used previously for spermatozoal concentration and subsequent fertilization. We investigated MC for micro-insemination spermatozoal transfer (MIST) of human spermatozoa from normal donors into hamster oocytes. MC resulted in reduced penetration of hamster oocytes, both after MIST [77.4% (41/53) versus 87.8% (43/49) for control; NS] and after exposure to zona-free hamster oocytes [60.8% (79/130) versus 72.7% (88/121) for control; P less than 0.05]. However, MIST under the zona resulted in better incorporation of sperm nuclei when compared with zona-free hamster oocytes, for spermatozoa exposed to micro-centrifugation (77.4 versus 60.8%, P less than 0.05) and controls (87.8 versus 72.7%, P less than 0.05). Polyspermy was higher after MIST [22.0% (9/41) versus 13.9% (11/79); NS] for MC+, and [25.6% (11/43) versus 13.6% (12/88); NS] for MC-. We conclude that MC does have a negative, but minimal effect on the fertility of human spermatozoa with respect to hamster oocytes. PMID- 2324264 TI - Propanediol alters intracellular pH and developmental potential of mouse zygotes independently of volume change. AB - Prior to treatment, mouse zygotes were incubated with acridine orange (AO) a fluorescent dye which fluoresces within a physiological pH range. The zygotes were then perifused with 1,2-propanediol (PROH) at rates of 0.18 mol/min, 0.36 mol/min and 1.0 mol/min and zygote volume and intracellular pH monitored. Zygotes perifused with phosphate-buffered saline maintained their initial volume and AO fluorescence. All of the zygotes exposed to PROH at a rate of 1 mol/min decreased in volume and lost their AO fluorescence by 10 min. The volume of the zygotes perifused at less than or equal to 0.36 mol/min was not altered. However, only 25% of the zygotes perifused at 0.36 mol/min maintained their fluorescence at 10 min and all lost their fluorescence by 15 min. At 0.18 mol/min 95% of the zygotes maintained their fluorescence at 10 min and 49% at 15 min. All of the PROH exposed zygotes lost their fluorescence by 20 min. Although 2-cell development was not affected by 3.0 M PROH for 2.5 min, blastocyst development was reduced compared with controls (P less than 0.05). Longer exposures resulted in a significant decrease in both 2-cell and blastocyst development. These data demonstrate that a 2-7-min exposure to greater than or equal to 2.5 M PROH alters both the intracellular pH and developmental potential. Since these detrimental effects are independent of volume changes and therefore intracellular PROH concentrations, it is postulated that PROH mediates its toxic action by directly altering the cell membrane. PMID- 2324265 TI - Non-surgical tubal embryo transfer. AB - Selective cannulation of the Fallopian tubes via the utero-tubal junction, without analgesia, anaesthesia or surgery, has been carried out to replace three embryos in a patient. Cannulating the Fallopian tubes did not appear materially to affect the transport of embryos or the receptivity of the endometrium for implantation. PMID- 2324266 TI - Pregnancy after direct intraperitoneal insemination of spermatozoa from a man with severe infertility, after unsuccessful application of other methods of assisted fertilization. AB - Direct intraperitoneal insemination (DIPI) is one of the least invasive strategies of assisted reproduction. Unexplained infertility and male sub fertility are the major indications for DIPI. It is otherwise well known that assisted procreation gives poor results in severe male infertility. This is a report of a pregnancy that occurred as a result of a direct intraperitoneal insemination of prepared spermatozoa characterized by a particularly severe astheno-teratozoospermia in a couple unsuccessfully treated with other, more invasive methods of assisted fertilization. PMID- 2324267 TI - Sperm chromosome studies in an infertile man with partial, complete asynapsis of meiotic bivalents. AB - Meiotic and sperm chromosome studies were carried out in two semen samples from an infertile man with a 46,XY karyotype, oligoasthenoteratozoospermia and abundant exfoliation of spermatogenic cells. Meiotic preparations showed partial, complete asynapsis in a large proportion of metaphase I figures observed, and absence of metaphase II figures, while 24 of the 30 sperm chromosome karyotypes analysed were normal. The remaining sperm karyotypes were as follows: one with structural abnormalities, one with both structural abnormalities and hypohaploidy and four with hypohaploidy. The total frequency of chromosomal abnormalities (6.7%) is similar to that obtained by us in normal men (10.9%). The frequency of spermatozoa with structural abnormalities (6.7%) was not significantly different from that obtained by us in normal men (6.9%). These results suggest that, in some cases, asynaptic spermatogenic cells do not proceed further than metaphase I and only normal germ cells continue spermatogenesis. PMID- 2324268 TI - Protein banding patterns of the outer membrane-enriched fraction of Bacteroides bivius. AB - Bacteroides bivius is a common anaerobe in female genital infections. Although protein banding patterns of outer membrane (OM) preparations of Bacteroides fragilis are well described and are homologous within the species, similar work has not been done with B. bivius. Our aims were to (i) characterize the OM banding patterns of B. bivius and compare them with those of other Bacteroides species and (ii) test clinical isolates of B. bivius against anti-B. bivius and anti-B. fragilis sera to identify different serogroups that might also exhibit different OM banding patterns. OM-enriched fractions of 27 clinical strains of B. bivius, 6 Bacteroides disiens strains, 10 B. fragilis strains, and 12 other Bacteroides strains were prepared, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed. Antisera to B. bivius ATCC 29303 and B. fragilis ATCC 25285 were raised in rabbits and tested against Bacteroides strains in an indirect enzyme-linked immunosorbent assay. All 27 B. bivius strains contained protein bands at 32, 27, 25, and 23 kilodaltons. This pattern was present in only 2 of 28 other strains; both of these were B. disiens. All B. bivius strains were reactive with the anti-B. bivius serum, while only 6 of 39 other strains (2 of 6 B. disiens) were reactive. Non-B. fragilis Bacteroides strains did not react with the anti-B. fragilis serum. Although there was marked homogeneity in the OM banding patterns of B. bivius, some B. disiens strains exhibited similar OM banding patterns. There appears to be some antigenic cross-reactivity between strains of B. bivius and B. disiens and very little with other Bacteroides species. These results may ultimately allow the development of rapid diagnostic tests for the B. bivius-B. disiens group.t PMID- 2324269 TI - Phenotypic characterization, cellular fatty acid composition, and DNA relatedness of aerococci and comparison to related genera. AB - Aerococci can be misidentified as streptococci, enterococci, pediococci, lactococci, or leuconostocs. To distinguish the genus and determine if another species is needed in the present taxon, we analyzed 37 aerococci for cellular fatty acids and compared them with 377 strains of gram-positive cocci, including the species type strains from each of the related genera. The cellular fatty acid profile of aerococci was distinguishable from other genera. Two relatively novel fatty acids found in the aerococci were identified as C16:1 omega 9c and C16:1 omega 9t. Eleven strains of aerococci (including a strain originally identified as "Gaffkya" species) were chosen for DNA-DNA reassociation studies with the type strain Aerococcus viridans ATCC 11563; DNAs from eight of these strains were more than 75% related to the type strain and had 1 to 4% divergence in related sequences. The remaining three strains were 60 to 70% related to the type strain, had 7 to 11.5% divergence, and may represent a second species, Aerococcus genospecies 2. beta-Glucuronidase, alpha-galactosidase, and beta-galactosidase were useful in characterizing the aerococci. PMID- 2324270 TI - Use of Haemophilus test medium for broth microdilution antimicrobial susceptibility testing of Streptococcus pneumoniae. AB - A recently described medium (Haemophilus test medium [HTM]) for antimicrobial susceptibility testing of Haemophilus influenzae was evaluated in this study for broth microdilution testing of Streptococcus pneumoniae. A total of 137 clinical isolates was tested against 11 antimicrobial agents, using Mueller-Hinton broth supplemented with 3% lysed horse blood in parallel with HTM. Inocula of 5 X 10(5) CFU/ml and incubation for 20 to 24 h were used with both media. All isolates of S. pneumoniae produced acceptable growth in both media, and MICs determined in HTM agreed closely with those determined in lysed horse blood. Drugs which provided a MIC within 1 log2 concentration difference in both media included penicillin (100%), ampicillin (98.0%), amoxicillin-clavulanate (100%), ampicillin sulbactam (100%), cephalexin (98.9%), cefaclor (96.8%), cefuroxime (99.0%), chloramphenicol (96.2%), tetracycline (96.2%), and erythromycin (100%). HTM MICs with trimethoprim-sulfamethoxazole were 1 to 2 log2 concentration increments higher in 92.0% of isolates than MICs determined in lysed horse blood. Based on the results of this study, HTM appears to represent a promising alternative medium for broth microdilution susceptibility testing of S. pneumoniae. PMID- 2324271 TI - Identification of coagulase-negative staphylococci by electrophoretic profile of total proteins and analysis of penicillin-binding proteins. AB - Analyses of total solubilized proteins and penicillin-binding proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were demonstrated to be accurate methods for the identification of coagulase-negative staphylococci. However, penicillin-binding protein profiles were found to be much clearer for the identification of these organisms to species level than was examination of the total solubilized proteins. By using the former technique, 13 reference strains were found to have species-specific penicillin-binding protein profiles, and 150 of 160 randomly collected clinical isolates were identified as belonging to eight of these species. A group of three clinical strains probably represents the recently described species Staphylococcus lugdunensis; the other seven clinical isolates belonging to five species remained unclassified. PMID- 2324273 TI - Agreement between visual and automated UniScept API readings. AB - The UniScept API system was evaluated for agreement of visual versus automated readings of both its identification panels and its antimicrobial susceptibility panels. The biochemical responses of 340 oxidase-negative and oxidase-positive fermentative bacterial cultures were read both visually and automatically in the UniScept API 20E system. Automated and visual readings agreed with 99.3% of the biochemicals. Of the 45 tests that disagreed, the tests for indole and citrate were most often in disagreement. A total of 470 fermentative and nonfermentative cultures were used in the UniScept MIC system to compare visual and automated readings of susceptibility results with 17 antimicrobial agents. Agreement within +/- 1 dilution occurred with 94.1% of the enteric fermenters and with 91.7% of the other cultures. Comparison of visual and automated readings resulted in very major discrepancies in 0.95% of the readings, with the largest percentage of discrepancies associated with glucose nonfermenters (1.8%). It was felt that an automated reading is an acceptable alternative to a visual reading of the biochemicals but that 0.95% was just within the acceptable range of the 1% allowable very major discrepancies in the automated reading of susceptibilities. PMID- 2324272 TI - Encapsulation of Staphylococcus aureus isolates from mastitic milk: relationship between capsular polysaccharide types 5 and 8 and colony morphology in serum-soft agar, clumping factor, teichoic acid, and protein A. AB - A total of 193 Staphylococcus aureus isolates from bovine, caprine, and ovine mastitis producing type 5 or 8 capsular polysaccharides were investigated for colony morphology in serum-soft agar and agglutinability by an anti-teichoic acid serum, after cultivation in modified staphylococcus medium no. 110. Also, 40 of these strains were cultivated in brain heart infusion and submitted to clumping factor and protein A detection tests. Considering capsular serotyping as a reference method, diffuse growth in serum-soft agar and inagglutinability by anti teichoic acid serum identified, respectively, 57.5 and 45% of encapsulated strains cultivated in brain heart infusion and 85.5 and 77.2% of those cultivated in modified staphylococcus medium 110. Consequently, these indirect techniques underestimated encapsulation and were greatly influenced by culture conditions. Whatever the medium used, diffuse colony morphology in serum-soft agar was generally characterized by a masking of teichoic acid and protein A. By contrast, these surface antigens were detected in association with compact morphology; the presence of a thin or discontinuous capsular material could explain this result. Moreover, the masking of teichoic acid and the removal of capsular polysaccharide by washing in saline suggest that type 8 capsular polysaccharide is more abundant and labile than type 5. PMID- 2324274 TI - Antibody responses to protein A in patients with Staphylococcus aureus bacteremia and endocarditis. AB - To assess the significance of antibody to Staphylococcus aureus protein A (SpA) in human sera, we developed a modified enzyme-linked immunosorbent assay (ELISA). SpA antibody levels in 23 patients with S. aureus endocarditis (IE), 21 patients with non-IE S. aureus bacteremia, and 33 controls were measured. Geometric mean levels of antibody to SpA were significantly higher in S. aureus IE patients (134 ELISA units [EU]) than in uninfected controls (52 EU; P less than 0.01). Also, a significantly greater proportion of S. aureus IE patients (12 of 23) and S. aureus non-IE bacteremia patients (11 of 21) had antibody levels greater than an arbitrary threshold of 100 EU compared with uninfected controls (0 of 23; P less than or equal to 0.001). However, no significant differences in geometric mean SpA antibody levels between the bacteremic patients with and without IE were noted. The sensitivity and specificity of this ELISA to distinguish patients with S. aureus IE from those with non-IE bacteremia were low (52 and 48%, respectively). There was a significant association between SpA antibody levels and either immunoglobulin G or immunoglobulin M teichoic acid antibody levels (r = 0.406, P less than 0.05; r = 0.571, P = 0.002, respectively). For patients from whom multiple sera were available (13 IE and 5 non-IE patients), SpA antibody levels were measured over time and showed a wide temporal variation of immune responses. We conclude that antibody responses to SpA can be measured in many patients with invasive S. aureus disease but that the levels are of insufficient sensitivity or specificity to be of clinical use as a diagnostic or prognostic test. PMID- 2324275 TI - Cultivation and characterization of spirochetes from cerebrospinal fluid of patients with Lyme borreliosis. AB - Attempts were made to culture spirochetes from cerebrospinal fluid samples of 105 patients suspected of having Lyme borreliosis with neurological complications. At the final evaluation, only 38 patients fulfilled the criteria of neuroborreliosis. Spirochetes were cultured from cerebrospinal fluid samples of four of these patients. All four patients had pleocytosis in their cerebrospinal fluid and a history of neurological symptoms of only 4 to 10 days in duration. Two of them had no detectable antibodies against any of the isolated spirochetes in their cerebrospinal fluid, both when tested with an enzyme-linked immunosorbent assay and when tested by immunoblotting. An antibody reaction against the homologous isolate that was distinctly stronger than that against the heterologous isolates was found in the serum and cerebrospinal fluid samples from one patient. The cells of the isolates were morphologically similar and showed a very similar protein pattern when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Cells of all isolates reacted with the monoclonal antibodies H5332 and H9724, which also react with Borrelia burgdorferi B31, the type strain. One isolate lost a major protein of 23 kilodaltons after subcultivation for 4 months. We conclude that isolation of spirochetes from cerebrospinal fluid might prove successful in clinically selected cases of Lyme borreliosis. PMID- 2324276 TI - Chemotaxonomic differentiation of legionellae by detection and characterization of aminodideoxyhexoses and other unique sugars using gas chromatography-mass spectrometry. AB - Legionellae have been differentiated previously by analyzing their carbohydrate contents by gas chromatography with flame ionization detection. In the present study, total ion mode gas chromatography-mass spectrometry (GC-MS) was used to detect a number of unusual sugars, including one that is structurally related to O-methyldideoxyheptoses. Increased sensitivity and selectivity for carbohydrate detection was achieved by selected ion-monitoring GC-MS. Two of the uncommon sugars previously discovered in the legionellae (X1 and X2) were identified as quinovosamine and fucosamine, respectively. Legionella pneumophila contained rhamnose and quinovosamine but not the quinovosamine isomer fucosamine. Tatlockia micdadei and Legionella maceachernii contained large amounts of rhamnose, fucose, and fucosamine but not quinovosamine. These two species were the only legionellae studied that contained another unusual sugar that is referred to as X3, pending determination of its structure. Fluoribacter dumoffi, Fluoribacter bozemanae, and Legionella anisa were varied in their carbohydrate contents, both within and between species, but could be distinguished from L. pneumophila and the T. micdadei and L. maceachernii group. Fluoribacter gormanii was unique among the legionellae in that it lacked both quinovosamine and fucosamine. Legionella jordanis contained other unusual carbohydrates in addition to quinovosamine. GC MS may have wide application in the differentiation of bacterial species. PMID- 2324277 TI - Genotypical variation of Campylobacter pylori from gastric mucosa. AB - In a previous study, the recurrence of the Campylobacter pylori infection after apparently successful antibacterial therapy was determined to be due to recrudescence rather than reinfection. Although the DNA patterns of pre- and posttreatment isolates were very similar, we detected minor differences between the two patterns in about one third of the patients. These differences were not artifacts, but originated in the coexistence in the stomach of (sub)populations of bacteria with slightly different chromosomal DNAs, plasmids, or both. The presence of such (sub)populations was probably caused by mutation in vivo, as mutation in vitro was demonstrated in one patient after the original isolate was subcultured 10 times. Minor differences were not correlated with a difference in susceptibility to the antibiotic(s) that was used. An additional conclusion of this investigation was that the results of plasmid analysis should be interpreted very carefully when this method is used as an epidemiologic marker in the investigation of C. pylori infections. PMID- 2324278 TI - Collagen binding, elastase production, and slime production associated with coagulase-negative staphylococci isolated from bovine intramammary infections. AB - Collagen binding, elastase production, slime production, and associated somatic cell counts were determined with 160 strains of coagulase-negative staphylococci isolated from bovine intramammary infections. Mean binding values for type I and II collagen with Staphylococcus epidermidis, S. chromogenes, and S. hyicus strains were 5.8, 6.6, and 7.4 and 4.3, 4.2, and 4.9%, respectively. Eleven of 28 (39.3%) S. epidermidis, 1 of 38 (2.6%) S. chromogenes, and 1 of 94 (1.1%) S. hyicus strains were elastase positive. Slime production was noted with 12 (42.9%) S. epidermidis, 1 (2.6%) S. chromogenes, and 11 (11.7%) S. hyicus strains. No differences in somatic cell counts were observed with type I or type II collagen binding, elastase production, or slime production with S. epidermidis or S. chromogenes. However, somatic cell counts associated with S. hyicus strains with collagen type I binding affinities of greater than 5 and type II binding affinities of greater than 3 were 320.7 x 10(3) compared with 163.9 x 10(3) for strains with lower binding affinities. PMID- 2324279 TI - Human serum antibody response to the presence of Aeromonas spp. in the intestinal tract. AB - A bacterial agglutination assay, a toxin-neutralizing assay, and an enzyme-linked immunosorbent assay (ELISA) were used to compare antibodies against intestinal Aeromonas strains in serum samples from healthy carriers (n = 6), from patients with acute (n = 15) or chronic (n = 8) gastroenteritis, from patients with gastroenteritis caused by other enteropathogenic bacteria (n = 3), and from healthy blood donors (n = 50). Evaluation of the bacterial agglutination assay showed that it was not very useful. The sensitivity of the ELISA in patients with acute or chronic aeromonas-associated diarrhea was 30% (7 of 23 patients were positive), whereas the specificity was 74% (13 of 50 healthy donors were positive). Positive results in the ELISA correlated with immunoglobulin M and immunoglobulin G responses to lipopolysaccharides of homologous Aeromonas strains, as determined by gel immunoradioassay and Western immunoblot analysis. The sera showed cross-reactions with heterologous Aeromonas strains and with Escherichia coli strains. The toxin-neutralizing assay was positive in 5 of 11 patients who had developed acute severe diarrhea associated with cytotoxin producing Aeromonas strains (46% sensitivity), whereas only 3 of 50 healthy donors had low serum titers of cytotoxin-neutralizing antibodies (94% specificity). All five patients were over 60 years of age. Cytotoxin-neutralizing activity was not observed in the sera of other groups of patients with aeromonads in their feces. We concluded that the three different serologic assays were not consonant with one another and that only the toxin-neutralizing assay distinguished patients with acute diarrhea from other groups of patients. PMID- 2324280 TI - Fluorogenic assay for differentiating Staphylococcus warneri and Staphylococcus hominis strains of bovine origin. AB - A fluorogenic assay for the detection of beta-glucosidase was developed as part of a simplified conventional method to distinguish Staphylococcus warneri and Staphylococcus hominis isolated from bovine body sites. The assay is based on the fact that strains of S. warneri produce beta-glucosidase, while strains of S. hominis do not. PMID- 2324281 TI - Vibrio cholerae bacteremia associated with gastrectomy. AB - Bacteremia due to Vibrio cholerae is rare. Each of 15 cases previously reported in the English language literature occurred in the setting of immune deficiency. We describe an instance of non-serogroup O1 V. cholerae septicemia in an otherwise healthy patient. Susceptibility to such infection may have been enhanced by a prior gastrectomy for duodenal ulcer. PMID- 2324282 TI - Increased recovery of Legionella micdadei and Legionella bozemanii on buffered charcoal yeast extract agar supplemented with albumin. AB - The recovery of Legionella micdadei and L. bozemanii serogroups 1 and 2 from infected guinea pig spleens was evaluated by using two culture media: buffered charcoal yeast extract agar with 0.1% alpha-ketoglutarate (BCYE alpha) and the same medium supplemented with 1% bovine serum albumin (ABCYE alpha). At the lowest dilution of spleen tissue (10(-1)), recovery of all strains of L. micdadei and L. bozemanii was more efficient on ABCYE alpha than on BCYE alpha. L. micdadei strains had higher recovery rates on ABCYE alpha after another 10-fold dilution, but recoveries of L. bozemanii were similar on both media. Recovery rates for most test strains were comparable on BCYE alpha and ABCYE alpha at the highest dilution (10(-3)) of tissue tested. The presence of albumin in BCYE alpha increased the recovery rate of L. micdadei more than that of L. bozemanii. The use of ABCYE alpha medium in place of BCYE alpha may improve the recovery of L. micdadei and L. bozemanii from clinical specimens. Preliminary studies indicate that this medium also enhances recovery of certain Legionella spp. from environmental samples. PMID- 2324283 TI - Two cases of Mycobacterium haemophilum infection in Canada. AB - In 1987, Mycobacterium haemophilum was isolated from cutaneous lesions, a lymph node, and the right eye of a male patient with acquired immunodeficiency syndrome and also from a cervical lymph node in a 3-year-old girl. These two cases are the first M. haemophilum infections to be reported in Canada. PMID- 2324284 TI - Rapid diagnosis by buffy coat smear of disseminated Mycobacterium avium complex infection in patients with acquired immunodeficiency syndrome. AB - A smear of the buffy coat of peripheral blood for acid-fast bacilli was assessed for sensitivity and specificity in the diagnosis of disseminated Mycobacterium avium complex (MAC) infection in acquired immunodeficiency syndrome (AIDS) patients. Seventeen AIDS patients with blood cultures positive for MAC had simultaneous quantitative blood cultures and buffy coat smears performed, as did 4 patients later proven not to have disseminated MAC. The sensitivity of the buffy coat smear for the detection of MAC was 35%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 22%. We conclude that the buffy coat smear is a rapid, simple, and specific method of diagnosis of disseminated MAC infection in AIDS patients, although it is not very sensitive. PMID- 2324285 TI - Impact of the BACTEC NR system in detecting Candida fungemia. AB - As a result of the growing importance of candidemia, various techniques for the detection of Candida spp. in blood have been designed with a view to speeding up the laboratory procedure. We have performed a retrospective comparison of the efficiencies of the conventional VACUTAINER system (Becton Dickinson Vacutainer Systems) and the BACTEC NR system (Johnston Laboratories, Inc.). During a 4-year period, 88,300 blood cultures were processed, with growth of Candida species in 552. The mean times required for the detection of growth were 7.55 days with the VACUTAINER system and 4.1 days with the BACTEC NR system (P less than 0.05). During the first week of incubation, the VACUTAINER system detected 56.1% of the candidemias and the BACTEC NR detected 93.6% (P less than 0.05). Use of the BACTEC NR therefore permits reduction of the incubation period from the previously established 4 weeks to a more convenient 7 to 14 days. PMID- 2324286 TI - Cloned polynucleotide and synthetic oligonucleotide probes used in colony hybridization are equally efficient in the identification of Escherichia coli. PMID- 2324287 TI - The learning-disabled medical student. PMID- 2324288 TI - 36- and 48-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol. AB - Aspects of neurobehavioral development were examined in 133 36-month- and 130 48 month-old children for whom prenatal exposure to marijuana, cigarettes, and alcohol had been previously ascertained and who have been assessed since birth. Parallelling earlier observations made with this sample at 12 and 24 months, prenatal exposure to cigarette smoking was significantly associated with poorer language development and lower cognitive scores at both 36 and 48 months after statistically controlling for confounding factors. Relatively low levels of maternal alcohol consumption, which had measurable effects at 24 and 36 months, no longer had significant relationships with outcome variables at 48 months of age. At 48 months, significantly lower scores in verbal and memory domains were associated with maternal marijuana use after adjusting for confounding variables. This negative relationship is the first reported association beyond the neonatal stage, and may represent a long-term effect of the drug upon complex behavior that, at a younger age, had not developed and/or could not be assessed. PMID- 2324290 TI - Electromyographic biofeedback with mental imagery and home practice in the treatment of children with muscle-contraction headache. AB - A multiple-baseline across subjects design was used to evaluate the effects of electromyographic (EMG) biofeedback on muscle-contraction headaches reported by two adolescent females. Subsequent to baseline, each child participated in seven treatment sessions conducted over an 8-week interval. Treatment sessions consisted of 10 min of adaptation (baseline), 15 min of EMG biofeedback, and 5 min of self-control during which the child continued to decrease muscle tension without feedback. Children were instructed to practice self-control of relaxation at home. Self-reports of headache frequency, duration and intensity were recorded throughout the study. Results indicate that headache activity was reduced as a function of EMG biofeedback, mental imagery, and home practice and remained below baseline levels during 6-month and 1-year follow-up assessments. Findings are discussed in terms of the paucity of published studies investigating the efficacy of EMG biofeedback as a treatment for pediatric muscle-contraction headache. PMID- 2324289 TI - The usefulness of reaction time tasks in studying attention and organization of behavior in young children. AB - Three studies explored reaction time procedures as a means of assessing sustained attention and response organization in preschoolers. In the first study, an auditory reaction time task was administered to 65 3.5-year-olds. Performance deteriorated over trials, paralleling results reported for older children and adults. Performance on the task was also related to the hyperactivity subscale of the Conners Parents' Questionnaire and to Stanford-Binet IQ. In a second cross sectional study, performance on a visual reaction time task improved significantly from 2.5 to 4.5 years. A third study demonstrated individual stability and reasonable test-retest reliability for all measures. The results suggest that reaction time tasks can be usefully employed with young children to measure developmental changes and individual differences in sustained attention and organization of behavior. PMID- 2324291 TI - Accuracy of symptom perception in childhood asthma. AB - Children's reports of their asthma symptoms are used as important data in the assessment and management of pediatric asthma, but little is known about the accuracy of such reports. Children's subjective perception of the level of asthma symptoms was correlated with peak expiratory flow rate measures on average of 34 observations for 37 children with asthma. Subjective/objective correlations for a given child varied from 0.86 to -0.16. The children's perceptual accuracy was not related to age or sex, or to duration or severity of asthma. Implications for clinical practice are discussed. PMID- 2324292 TI - Mental health referral: a weak link in comprehensive care of children with chronic physical illness. AB - Although children with chronic medical conditions are at increased risk for mental health problems, they and their families receive few mental health services. For a number of reasons, it is unusually difficult to refer these youngsters to traditional mental health resources and this may contribute to the paucity of services that they receive. Significant barriers to referral are contributed by each participant in the process: families, medical staff, and mental health providers. Alternative approaches to the delivery of services to this high-risk population are suggested. PMID- 2324293 TI - Behavioral problems in children of torture victims: a sequel to cultural maladaptation or to parental torture? PMID- 2324294 TI - Rage, rage against the dying of the light: a lament for needless death. PMID- 2324295 TI - Predictors of outcome among adult psychiatric first-admissions. AB - This study comparatively evaluated the prognostic potential of 10 demographic and clinical factors previously associated with psychiatric outcome. The longitudinal design employed intensive, structured, reliable interview techniques. One hundred forty-five subjects from a representative sample (N = 217) of community mental health catchment area first lifetime admissions were assessed at hospitalization and at 2-year follow-up. Predictors examined included premorbid functioning, overall health-sickness, diagnostic severity, social class, sex, age, IQ, race, and life events. Outcome was assessed multidimensionally with absolute-level and residualized indices of functioning and symptomatology. Phillips Premorbid Status and social class emerged from correlation and multiple regression analyses as the best predictors of functioning level and overall clinical status, while IQ was the most prominent indicator of symptomatology changes. Results support the notion that a general social competence factor predicts to psychiatric outcome across the entire spectrum of severe disorders. PMID- 2324296 TI - A clinical study of the automated assessment of intelligence by the Mill Hill Vocabulary test and the Standard Progressive Matrices test. AB - As part of the Leicester/DHSS project on microcomputer-aided assessment, 274 patients at five clinical sites were assessed with either a computerized version or the standard version of the Mill Hill Vocabulary (Synonyms) test. Of this group, 178 were retested on the alternative version of the test. Similarly, 184 patients were tested with either a computerized version or the standard version of the Standard Progressive Matrices test, of whom 129 were retested on the alternative test form. High correlations were found between the standard and computerized versions for both tests. For the Mill Hill Vocabulary test, no significant difference was found between test versions for first administration, and the vast majority of retested subjects had very similar scores on each version. On the Standard Progressive Matrices, however, subjects obtained significantly lower scores on the computerized test. It is concluded that whereas the computerized Mill Hill Vocabulary test could be used in place of the standard version of clinical settings, the computerized Standard Progressive Matrices test could not be used. PMID- 2324297 TI - Standardization of the Whitaker Index of Schizophrenic Thinking (WIST) in a Mexican population: a multivariable study. AB - This study reports a study of Spanish translation of Form A of the Whitaker Index of Schizophrenic Thinking (WIST) administered to 104 Mexican subjects: 40 schizophrenic (20 acute and 20 chronic) and 64 nonschizophrenic (10 nonschizophrenic hospitalized, 10 alcoholics, and 44 normals). A multiple regression analysis was carried out in order to evaluate the existing relation between each of the MMPI and WIST forms. The results suggest that this translation effectively discriminates between schizophrenics and nonschizophrenics on the WIST Total Score, Time, and Index. A cut-off of 23 on the WIST Index correctly identified 79% of the total subjects. The WIST, as well as the MMPI, separately detects in a reliable way schizophrenic subjects, but the correlation between the Index of the WIST and the MMPI 8 or schizophrenia scale by itself is not significant. PMID- 2324298 TI - ICD-9-CM classification coding in psychiatry. AB - The question was addressed how well mental health professionals were able to translate diagnostic formulations into ICD-9-CM codes. This was done with three coder groups and under two conditions. It was found that there was insufficient interrater agreement on the ICD-codes in all groups and conditions. This finding then was related to the inadequacies of the ICD-system itself. It was concluded that current mental health statistics that are based on the ICD-9-CM coding system are without scientific value. PMID- 2324299 TI - The Brief Psychiatric Rating Scale (BPRS) and the Nurses' Observation Scale for Inpatient Evaluation (NOSIE) in the evaluation of positive and negative symptoms. AB - Positive and negative a priori symptom scales were operationalized with the BPRS and the NOSIE. Acutely and consecutively admitted psychiatric patients (N = 247) were rated with these scales. Research questions dealt with the psychometric properties of the scales. It was found that the positive symptom scales had sufficient internal consistency; the negative scales did not. Diagnostic groups could be distinguished better with the positive symptom (PS) than with the negative symptom (NS) scales. The outcome of this research suggests that the positive and negative symptoms distinction is less meaningful in cross-sectional research, in which acute patients are rated, than in longitudinal research. PMID- 2324300 TI - Test of MCMI black norms for five scales. AB - A 2 x 2 x 2 MANOVA was used to analyze the effects of race (Black vs. White), education (high school graduate vs. less than high school education), and diagnosis (schizophrenic vs. nonschizophrenic) on the MCMI Asocial, Avoidant, Schizotypal, Psychotic Thinking, and Psychotic Delusions scales that were obtained from 310 newly admitted psychiatric patients. The scales were selected because, according to the MCMI manual (Millon, 1983), they would be most apt to show differences between the schizophrenic and nonschizophrenic patients who participated in this study. The special norms for Black and White patients provided in the MCMI manual supplement (Millon, 1984) were used to compute the scale scores for the patients in this study. Race was the only significant (p less than .001) effect. Blacks scored higher than Whites on the Asocial, Avoidant, Psychotic Thinking, and Psychotic Delusions (p less than .04 for all scales). The results are discussed in terms of racial bias diminishing the usefulness of the MCMI. PMID- 2324301 TI - MMPI differences for renal, psychiatric, and general medical patients. AB - Renal failure has both medical and psychological implications. Indeed, various psychiatric problems related to end-stage renal disease have been reported in the literature; however, the focus has been on anxiety and depression. While previous research has dealt with the comparisons of patients with renal failure, few studies have investigated the comparison of renal patients with psychiatric and general medical patients. The present study compared renal patients (N = 24) with a group of depressed psychiatric patients (N = 24) and a group of general medical patients (N = 24) on the MMPI. The results suggested that the renal group presented a psychological profile that more closely resembled that of the depressed psychiatric group than that of patients with other chronic medical conditions. PMID- 2324302 TI - Family dysfunction in normal weight bulimic and bulimic anorexic families. AB - A group of 24 normal weight bulimics and 13 bulimic anorexics were compared with each other and a normal control group (n = 41) on two self-report measures of family functioning (Family Environment Scale and Family Dynamics Survey). The two bulimic groups perceived their families as more dysfunctional than did the normal control group on the dimensions of cohesion, expressiveness, conflict, recreational orientation, emotional support, communication, and need for counseling. There were few significant differences in the family perceptions of the two bulimic groups. PMID- 2324304 TI - Notes on the reliability of Wechsler short forms. AB - Information is provided on the reliability of random short forms of Wechsler's intelligence scales and on the reliability of short forms that reduce the number of items within subtests rather than the number of subtests. The results demonstrate how much better than random the most reliable short forms of the scales are. They also show that reducing the number of items within subtests rather than the number of subtests exacts a steep price in reliability. PMID- 2324303 TI - Luria Memory Words Test and Wechsler Memory Scale: comparison of utility in discriminating neurologically impaired from controls. AB - Memory deficits are among the most common initial complaints of patients who are suffering from neurological disorders. The present study compared the relative clinical utility of the Wechsler Memory Scale and the Luria Memory Words Test in differentiating brain-damaged (N = 60) from non-brain-damaged patients (N = 60). Separate stepwise regression analyses selected five variables from each test that accounted for the greatest between-group variance. Separate discriminant functions then were computed that used the WMS and the Luria Words variables selected through the regression analyses. The WMS correctly classified 72% of the subjects, whereas the Luria Words correctly classified 76% of the subjects. A final discriminant function was computed that used all 10 variables and resulted in a classification accuracy of 86%, with 6% false positives and 6% false negatives. Results are discussed relative to the use of each instrument in both a general psychological assessment situation and when specific memory functioning is in question. PMID- 2324305 TI - Short forms of the WAIS-R with psychiatric inpatients: a comparison of techniques. AB - The relative performance of six Wechsler Adult Intelligence Scale-Revised short forms (Brooker & Cyr, 1986; Reynolds, Wilson, & Clark, 1983; Silverstein, 1982) was examined for a group of psychiatric inpatients (N = 50). Short forms were evaluated according to their ability to predict the Full Scale IQ using regression analysis. The standard error of estimate was significantly smaller for Silverstein's (1982) four-subtest short form, which consists of Vocabulary, Arithmetic, Picture Arrangement, and Block Design. Using the Silverstein (1982) tables, 90% of the short form IQs fell within +/- 6 points of the actual Full Scale IQ. PMID- 2324306 TI - Neurocognitive deficits of alcoholism: an intervention. AB - This study investigated the impact of cognitive retraining on a sample of neurocognitively impaired alcoholics (N = 45). The treatment group received training on a hierarchical cumulative learning program. In this paradigm, the subjects mastered an isolated concept to automaticity, at which point a second and then a third concept were added. The training group demonstrated significantly improved performance over the practice and control groups on the three measures taken from the Wisconsin Card Sorting Test: total number of categories, perseverative errors, and nonperseverative errors. Neither the practice nor the control group exhibited significantly improved performance. These data lend support to an information processing perspective and are at odds with research that infers that neurophysiological substrates preclude normal functioning in alcoholics and argues that mere exposure of alcoholics to training stimuli prompts significant improvements. Treatment implications are discussed. PMID- 2324307 TI - MCMI comparisons of cocaine abusers and heroin addicts. AB - Cocaine addicts (N = 107) and opiate addicts (N = 86) in treatment for drug abuse were compared on the MCMI. Univariate analyses revealed that cocaine abusers showed more traits of the antisocial personality style, whereas heroin addicts evinced more problems with anxiety and somatic distress, probably related to residual problems of withdrawal, and alcohol abuse. Multivariate analyses revealed four distinct clusters (MCMI patterns 456', 865', 56', and 8') that aligned by underlying personality style and clinical syndrome expression rather than by drug of choice. Ideographic analyses further demonstrated consistencies in prevalence rates of DSM-III-R personality disorders. Results do not support the pharmacodynamic theory of drug abuse. It was concluded that the similarities in personality between these two groups are greater than their differences. PMID- 2324308 TI - Methodological variations in the use of the MMPI for diagnosis of borderline personality disorder among alcoholics. AB - Methodological variations in the scoring and interpretation of the MMPI and their effects on discrimination between borderline and non-borderline personality disordered alcoholics were investigated. Subjects were 49 male and female inpatient alcoholics in an Icelandic psychiatric hospital. Gunderson's Diagnostic Interview for Borderlines and the Michigan Alcoholism Screening Test were used to diagnose borderline personality disorder and alcoholism, respectively. Scoring and interpretation of the MMPI were varied in terms of the use and non-use of high F-scale profiles, and their impact on the frequency of various code types among borderline and non-borderline personality disordered alcoholics was considered. It was found that such methodological variations do not affect the frequency of some profile types, and, consequently, the discrimination between the diagnostic groups. Studies and coding systems should consider methodological variations in the scoring and interpretation of MMPI profiles and their consequent effects on diagnosis. PMID- 2324309 TI - Validity of the MCMI Drug Abuse Scale with drug abusing and psychiatric samples. AB - The validity of the Drug Abuse Scale (T) from the Millon Clinical Multiaxial Inventory (MCMI) was studied by administering the MCMI to 75 White male veterans who were seeking treatment for opioid or cocaine dependence and 60 White male veterans without diagnoses of drug dependence who were receiving psychiatric care. Only (39.4%) of the drug-abusing sample was classified correctly by obtaining base rate (BR) scores above the clinical relevant cut-off of 74, whereas, only 12% of the psychiatric sample was misclassified by having obtained a BR above 74. The results suggest that the MCMI T Scale is limited in its ability to identify drug users, but is also unlikely to misclassify psychiatric patients as drug abusers when they are not. The authors urge caution in using the Drug Abuse Scale for the purpose of identifying drug abusers. PMID- 2324310 TI - Human photoreceptor topography. AB - We have measured the spatial density of cones and rods in eight whole-mounted human retinas, obtained from seven individuals between 27 and 44 years of age, and constructed maps of photoreceptor density and between-individual variability. The average human retina contains 4.6 million cones (4.08-5.29 million). Peak foveal cone density averages 199,000 cones/mm2 and is highly variable between individuals (100,000-324,000 cones/mm2). The point of highest density may be found in an area as large as 0.032 deg2. Cone density falls steeply with increasing eccentricity and is an order of magnitude lower 1 mm away from the foveal center. Superimposed on this gradient is a streak of high cone density along the horizontal meridian. At equivalent eccentricities, cone density is 40 45% higher in nasal compared to temporal retina and slightly higher in midperipheral inferior compared to superior retina. Cone density also increases slightly in far nasal retina. The average human retina contains 92 million rods (77.9-107.3 million). In the fovea, the average horizontal diameter of the rod free zone is 0.350 mm (1.25 degrees). Foveal rod density increases most rapidly superiorly and least rapidly nasally. The highest rod densities are located along an elliptical ring at the eccentricity of the optic disk and extending into nasal retina with the point of highest density typically in superior retina (5/6 eyes). Rod densities decrease by 15-25% where the ring crosses the horizontal meridian. Rod density declines slowly from the rod ring to the far periphery and is highest in nasal and superior retina. Individual variability in photoreceptor density differs with retinal region and is similar for both cones and rods. Variability is highest near the fovea, reaches a minimum in the midperiphery, and then increases with eccentricity to the ora serrata. The total number of foveal cones is similar for eyes with widely varying peak cone density, consistent with the idea that the variability reflects differences in the lateral migration of photoreceptors during development. Two fellow eyes had cone and rod numbers within 8% and similar but not identical photoreceptor topography. PMID- 2324311 TI - Innervation of the serotonin-immunoreactive cells distributed in the wall of the common carotid artery and its branches in the chicken. AB - In the chicken, serotonin-immunoreactive cells were widely distributed not only in the carotid body but also in the wall of the common carotid artery and around each artery arising from the common carotid artery. Almost all of the serotonin cells in the wall of the common carotid artery were intensely immunoreactive to the neuropeptide Y, met- and leu-enkephalin antisera, whereas in the carotid body only a few cells were immunoreactive to these antisera. Innervation of the serotonin cells in and around arteries of chickens was investigated by immunohistochemistry and electron microscopy, in comparison with that of the carotid body. The serotonin cell groups in and around arteries, as well as the carotid body, received numerous peptidergic nerve fibers. Calcitonin gene-related peptide (CGRP)- and substance P-immunoreactive varicose nerve fibers were densely distributed, and somatostatin-immunoreactive fibers were moderately distributed in the serotonin cell groups. Galanin- and vasoactive intestinal peptide (VIP) immunoreactive fibers were sparsely distributed in the cell groups. By electron microscopy, the serotonin cells in and around arteries were characterized by the presence of numerous dense-cored vesicles, 70-220 nm in diameter. The granule containing cells were in close association with numerous axons. Naked axons regarded axon terminals were frequently apposed on the granular cells. The axon terminals were usually long and often partly invested the granular cells. Numerous synaptic junctions were detected along the contact between the granular cells and axon terminals. Most of the synaptic junctions showed afferent morphology; the secretory granules were accumulated near and attached to the asymmetrical membrane thickenings. Thus, the serotonin cells in and around arteries, like the carotid body, constitute chemoreceptive tissue. PMID- 2324312 TI - Postnatal gliogenesis in the nerve fiber layer of the rabbit retina: an autoradiographic study. AB - Cell proliferation was studied in the retina of rabbits at various postnatal stages. Autoradiography was performed with animals that received a single injection of 3H-thymidine and were sacrificed 1 hour later. This short survival time allowed the determination of the position of a cell undergoing DNA synthesis at that moment. Between birth and day 6, cells engaged in DNA synthesis were seen in the inner nuclear layer (INL) of the entire retina. Cytogenesis ceases in this layer after the first postnatal week. Few labeled cells were detectable in the INL at day 9; these were found close to the ora serrata. Thus neurogenesis, which is known to occur in this layer of the retina, ceases by that time. In the nerve fiber layer (NFL), labeled cells were found at all ages between birth and day 27, which was the oldest stage examined in this study. By using horizontal sections through the NFL of entire retinae, it was observed that almost all labeled cells were confined to the medullary ray region, which is the neuroglia (astrocyte and oligodendrocyte)-bearing part of the NFL. Microglial cells, the only cellular elements present in the NFL outside the medullary ray region, were rarely labeled, and thus do not play a major role in gliogenesis occurring in the NFL. In addition to neuroglia, some endothelial cells were labeled after day 9. It is concluded that gliogenesis taking place in the NFL persists after the cessation of neurogenesis, suggesting that both processes occur independently. PMID- 2324313 TI - Analysis of taste bud innervation based on glycoconjugate and peptide neuronal markers. AB - Primary gustatory neurons and their peripheral and central processes were evaluated histochemically in the geniculate and petrosal cranial nerve ganglia, lingual fungiform taste buds, and the nucleus of the solitary tract (NST) using 1) the plant lectin Griffonia simplicifolia I-B4, which binds specifically to D galactose residues and selectively labels primarily nonpeptide-containing peripheral somatosensory neurons, and 2) calcitonin gene-related peptide immunoreactivity (CGRP-IR), which labels most peptidergic somatosensory neurons. Lectin reactivity was expressed by the vast majority of geniculate and petrosal ganglion cells, while CGRP-IR labeled very few cells. Peripherally, gustatory intragemmal axons penetrating fungiform taste buds were labeled only by the lectin and were depleted following chorda tympani transection. However, both lectin-labeled and CGRP-IR subpopulations of somatosensory perigemmal axons surrounding the taste buds were observed and were eliminated by section of the lingual nerve. The differing brainstem projection patterns of lectin-reactive vs. CGRP-IR central axons reflected their distinct ganglionic origins and the differential distributions of lectin reactivity and CGRP-IR among taste buds. Central lectin-reactive terminals were found throughout the entire rostrocaudal extent of the NST, including its rostral lateral "gustatory" zone; the extensive lectin-reactive visceral afferent projection can be presumed to have originated mainly from the large proportion of lectin-labeled neurons in the nodose ganglion. The lectin also prominently and selectively labeled the area postrema. CGRP-IR central terminals, however, was relatively sparse and restricted primarily to the caudal and medial "visceral" divisions of the NST. The results are discussed with respect to the possible functional implications of cell surface glycoconjugate expression by gustatory axons innervating taste bud receptor cells of the tongue. PMID- 2324314 TI - Branching patterns of corticospinal axon arbors in the rodent. AB - Despite extensive study of corticospinal connections in a variety of species, little is known about the detailed morphology of corticospinal axon arbors. Results in previous studies of primates based on intra-axonal filling with horseradish peroxidase (HRP) staining of a limited sample of fibers suggest that corticospinal arbors branch widely to multiple motoneuronal pools. To determine whether this pattern of corticospinal connectivity is present in nonprimate species as well, we studied the branching patterns of corticospinal axon arbors in a rodent species, the golden hamster. The axons were labeled by iontophoretic injection of Phaseolus vulgaris-leucoagglutinin (PHA-L) into small regions of the forelimb and hindlimb sensorimotor cortex, and immunohistochemistry with the peroxidase-antiperoxidase (PAP) method was used to reveal fine details of terminal arbors within the cervical and lumbar enlargements of the spinal cord. As in higher mammals, corticospinal connections are topographically organized. Moreover, corticospinal axons arising from somatosensory cortex project primarily to the dorsal horn, whereas those from motor cortex terminate most heavily in the ventral horn. This differential projection pattern, not previously demonstrated in rodents, implies functional differences between somatosensory and motor components of the corticospinal pathway. Reconstruction of corticospinal arbors in the ventral horn showed that in both cervical and lumbar spinal cord segments, axons branch widely into interneuronal regions. A surprising number appear to extend into motoneuron cell groups, and some of these axons branch into multiple motoneuronal pools. Widely divergent corticospinal axons that branch to multiple motoneuron pools have been shown to mediate activity in functionally related muscle groups of the primate forearm. The present results suggest that in other species, such as the rodent, a similar divergence of corticospinal arbors may also function to facilitate activity in subsets of muscles. PMID- 2324315 TI - Telodendrial contact of HRP-filled photoreceptors in the turtle retina: pathways of photoreceptor coupling. AB - Synaptic contacts of photoreceptors in the turtle retina were studied by intracellular injection of horseradish peroxidase (HRP) and electron microscopy. Both cone and rod photoreceptors radiated basal processes (telodendria) from their terminal endings. These telodendria ran laterally in the outer plexiform layer. The telodendria of cones gave rise to many fine branches that penetrated synaptic cavities of several neighboring cones. Tips of these branches terminated near the walls of synaptic cavities. Some of the telodendrial contact formed two types of basal junction: symmetrical and punctate. The distribution of cones that made telodendrial contacts with the HRP-filled cone were quantitatively investigated. Green-sensitive cones (n = 3) made telodendrial contacts with neighboring red- and blue-sensitive cones, blue-sensitive cones (n = 4) with red- and green-sensitive cones, and red-sensitive cones (n = 9) with red- and green sensitive cones. In contrast to these cone connections, rod telodendria did not penetrate neighboring photoreceptors. Direct synaptic contacts were not found between rods and cones. Our results clarify the variety of cone couplings in turtle retina: the three chromatic classes of cones are selectively coupled by the basal junctions at the ends of telodendrial processes. PMID- 2324316 TI - Vomeronasal and olfactory nerves of adult and larval bullfrogs: I. Axons and the distribution of their glomeruli. AB - The distribution of primary olfactory and vomeronasal (VMN) glomeruli is demonstrated in the forebrain of the larval (stage III tadpole) and adult bullfrog. Olfactory glomeruli are massed at the anterior end of the olfactory bulb; farther posterior, they are located at the periphery and then become distributed in a superficial layer all along the ventral surface of the bulb. Glomeruli of the accessory olfactory bulb (AOB) of the tadpole are less compact and show larger dendritic profiles and fewer synaptic junctions per unit area than those of the adult AOB. Axons of both tadpole and adult VMN nerve are ultrastructurally indistinguishable from those of the primary olfactory nerve; in comparing VMN axons of tadpole and adult, however, differences were observed in the number of neurofilament profiles in axons at the proximal and distal ends of the VMN nerve. Counts of neurofilament profiles in the two ends of the nerve suggest that neurofilament segments accumulate near terminations of their axons. The VMN nerve of tadpole and adult frog are roughly the same size, and calculations indicate that they contain comparable numbers of axons. The primary olfactory nerve of the tadpole is estimated to contain about 660,000 axons; the adherent VMN nerve of the tadpole contains about 270,000 axons (a ratio of about 2.5:1). In the adult, the ratio of primary to VMN axons is about 64:1, reflecting the quantitative growth of the primary olfactory nerve with development from an aquatic tadpole to an air-breathing adult. PMID- 2324317 TI - Vomeronasal and olfactory nerves of adult and larval bullfrogs: II. Axon terminations and synaptic contacts in the accessory olfactory bulb. AB - The ultrastructure of the accessory olfactory bulb (AOB) of the bullfrog tadpole and adult was examined, and the main difference between tadpole and adult is that the latter is more compact and shows more synapses. Except for vomeronasal (VMN) glomeruli, the AOB is not highly organized, with mitral cell neurons scattered throughout the neuropil. VMN axon terminals form asymmetric synapses with mitral cell dendrites in glomeruli; in VMN axon terminals, dense-cored vesicles are seen along with the more abundant lucent vesicles 40-50 nm in diameter. Counts indicated that more than 90% of the dendro-dendritic synapses between mitral cells and presumed granule cells are of the asymmetrical type, and reciprocal asymmetrical-symmetrical synapses are not common. Lucent vesicles with round or slightly ellipsoidal profiles and less abundant dense-cored vesicles 60-90 nm in diameter are found in pre- and postsynaptic dendrites; sometimes the dense-cored vesicles lie against or near the presynaptic membrane. Microtubules were often seen to be closely associated with pre- and postsynaptic elements of dendro dendritic synapses. The most characteristic feature of mitral cell bodies, apart from their large size, is an extensive Golgi system that may extend well into their major dendritic extensions. Dense-cored vesicles are associated with Golgi membranes, from which they probably originate. Centrioles are associated with the Golgi system, and some become basal bodies and give rise to cilia in some mitral cells. PMID- 2324318 TI - Morphology of rat spinal motoneurons with normal and hormonally altered specificity. AB - Potential determinants of motoneuronal morphology were examined by using a sexually dimorphic, steroid-sensitive neuromuscular system in the rat spinal cord. In males, the spinal nucleus of the bulbocavernosus (SNB) innervates the perineal muscles bulbocavernosus (BC) and levator ani (LA), and the dorsolateral nucleus (DLN) innervates the ischiocavernosus muscle (IC). Adult females normally lack these motoneurons and the peripheral targets. Prenatal exposure of females to the androgen dihydrotestosterone propionate (DHTP) partially masculinizes this neuromuscular system and alters moto-neuron-to-muscle specificity, resulting in retained SNB target muscles anomalously innervated by motoneurons in the DLN. Because the morphology of SNB and DLN motoneurons normally differs significantly, the influence of spinal cord location and peripheral target on motoneuron morphology can be directly compared. Injection of cholera toxin conjugated to horseradish peroxidase (CTHRP) into the LA of DHTP-treated females labeled motoneurons predominantly in the SNB. These (SNB-LA) motoneurons in DHTP females were identical in all morphological measures to those of normal males. CTHRP injection into the BC of DHTP females labeled motoneurons in both the SNB and the DLN. SNB-BC motoneurons in DHTP females resembled those of normal males in process number and orientation, but were significantly smaller in dendritic length per motoneuron and in soma size. The DLN motoneurons anomalously projecting to the BC in DHTP females differed significantly from SNB-BC motoneurons in soma size and number and orientation of primary processes. However, these motoneurons were identical in all respects to DLN-IC motoneurons in DHTP females; DLN-IC motoneurons were similar to those of normal males in the orientation of their dendritic arbor, but were significantly smaller in dendritic length, soma size, and number of primary processes. These comparisons make it clear that DHTP selectively affects motoneuronal specificity and morphology in specific motoneuron classes. Further, motoneuronal morphology in the SNB/DLN system appears to be influenced more by spinal cord location than by peripheral target. PMID- 2324319 TI - Organization of adrenergic inputs to the paraventricular and supraoptic nuclei of the hypothalamus in the rat. AB - Anterograde transport, retrograde transport, and immunohistochemical techniques were used to characterize the organization of neural inputs to the paraventricular (PVH) and supraoptic (SO) nuclei from the C1, C2, and C3 adrenergic cell groups in the rostral medulla. The results are as follows: 1) Phenylethanolamine-N-methyltransferase-immunoreactive (PNMT-IR) fibers and terminals were distributed to all parts of the parvicellular division of the PVH; the dorsal and dorsal medial subdivisions received the most prominent inputs, the lateral and ventral medial parts the least. Sparse terminal fields were found consistently in the magnocellular division of the PVH and in the SO. 2) A combined retrograde transport-immunohistochemical method was used to estimate the number and proportion of cells in the regions of the C1, C2, and C3 cell groups that contribute to the PNMT-IR innervation of the PVH. On average, 232 +/- 37 retrogradely labeled cells in the C1 cell group, 73 +/- 32 in the C2 cell group, and 96 +/- 26 in the C3 group stained positively for PNMT-IR. These values comprised 70%, 84%, and 89%, respectively, of all retrogradely labeled neurons in these regions. 3) Fibers and terminals arising from the regions of each of the three adrenergic cell groups were labeled by local injections of the anterogradely transported plant lectin PHA-L. Each component projection was found to distribute in a very similar fashion and to mimic the overall distribution of PNMT-IR; differential projection patterns within the PVH or SO were not seen consistently following deposits in any of the individual adrenergic cell groups or at different rostrocaudal levels of any individual cell group. 4) A dual anterograde tracing (PHA-L)-immunohistochemical (PNMT) labeling method revealed an appreciable number of varicosities arising from the regions of C1, C2, and C3 cell groups to contain PNMT-IR. These results suggest that adrenergic inputs to the PVH and SO, while arising from distinct medullary cell groups and presumably relaying different types of sensory information, are in a position to influence similar groups of parvicellular neurosecretory and/or autonomic-related projection neurons. PMID- 2324320 TI - Immunolabelling by a newt retinal pigment epithelium antibody during retinal development and regeneration. AB - The binding of RPE-1, a mouse monoclonal antibody selective for newt retinal pigment epithelium, was followed in eyes undergoing embryonic development and retinal regeneration. Using the indirect immunofluorescence technique on frozen sections, we observed bright and continuous labelling exclusively in the retinal pigment epithelium (RPE) of normal adult newts, but labelling became diminished near the ora serrata region and stopped abruptly at the ciliary margin. During development, labelling was not detected in the retinal pigment epithelium (RPE) until the formation of photoreceptor outer segments and was not observed in any other ocular tissue. There was no correlation between the appearance of pigment in retinal pigment epithelial cells and their labelling with the RPE-1 antibody. Furthermore, albino salamander embryos showed the same pattern of labelling with RPE-1 as that seen in age-matched pigmented animals. During retinal regeneration, RPE cells were labelled less intensely, but heavy labelling was observed in the newly formed retinal cells. With time, labelling in regenerated retina receded, so that by the end of regeneration, labelling by RPE-1 was once more restricted to the RPE cells. The identification of RPE-1 as a marker for postmitotic retinal neurons about to undergo differentiation provides a promising approach for further studies of regeneration with the help of molecular tools. PMID- 2324321 TI - Seasonal changes in vasopressin in the brain of the garden dormouse (Eliomys quercinus L.). AB - The distribution of vasopressin in the brain of the garden dormouse (Eliomys quercinus L.) was examined by immunocytochemistry at different times of the year. In spring-summer, sexual dimorphism in the density of vasopressin labeling was observed in several areas of the brain. In these regions, such as the lateral septum and the nucleus of the vertical limb of the diagonal band of Broca, male garden dormice showed more vasopressin immunoreactivity than their female counterparts. In autumn-winter, at the time of hibernation, vasopressin was undetectable in the sexually dimorphically innervated brain regions in males as well as females. In early spring, there was large variation in vasopressin staining in the male brain, whereas the female brain was consistently lacking in vasopressin labeling. In brain regions that exhibited no sexually dimorphic innervation in the summer, vasopressin labeling remained the same throughout the year. The difference in the amount of vasopressin immunoreactivity in males in summer and winter correlated significantly with differences in testes weight. In early spring, because of interindividual variations in the start of sexual activation, testes size does not correlate with the density of vasopressin immunoreactivity. Similar seasonal variations in density of vasopressin labeling in the brain were also observed in the European hamster (Cricetus cricetus). In this animal, central vasopressin infusion during the winter prevents hibernation. The presence of a similar pattern of changing vasopressin content in another hibernator, the garden dormouse, suggests an important role for this neuropeptide in seasonal functions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324322 TI - Anatomical studies of dorsal column axons and dorsal root ganglion cells after spinal cord injury in the newborn rat. AB - The response of dorsal column axons was studied after neonatal spinal overhemisection injury (right hemicord and left doral funiculus). Rat pups (N = 11) received this spinal lesion at the C2 level within 30 hours after birth. The cauda equina was exposed 3 months later in one group of chronic operates (N = 5) and in a group of normal adults (N = 2), and all spinal roots from L5 caudally were cut bilaterally; 4 days later the spinal cord and medulla were processed for Fink-Heimer impregnation of degenerating axons and terminals. In a second group of chronic operates (N = 6) and normal adult controls (N = 4) the left sciatic nerve was injected with a cholera toxin-HRP conjugate (C-HRP), followed by a 2-3 day transganglionic transport period, and then the spinal cord and medulla were processed with tetramethylbenzidine histochemistry. Both control groups have a consistent dense projection in topographically adjacent regions of the dorsal funiculus and gracile nucleus. However, there is no sign of axonal growth around the lesion in either group of chronic experimental operates. Instead, there is a decreased density of projection within the dorsal funiculus near the lesion site. Many remaining C-HRP labeled axons in the experimental operates have abnormal, thick varicosities and swollen axonal endings (5-10 microns x 10-30 microns) within the dorsal funiculus through several spinal segments caudal to the lesion. Ultrastructural analysis of the dorsal funiculus in three other chronic experimental operates reveals the presence of numerous vesicle filled axonal profiles and reactive endings which appear similar to the C-HRP labeled structures. Transganglionic labeling after C-HRP sciatic nerve injections (N = 4) and retrograde labeling of L4, L5 dorsal root ganglion neurons after fast blue injections of the gracile nucleus (N = 6) both suggest that all dorsal column axons project to the gracile nucleus in the newborn rat. Dorsal root ganglion (DRG) cell survival following the neonatal overhemisection injury was also examined in the L4 and L5 DRG. DRG neurons that project to the gracile nucleus were prelabeled by injecting fast blue into this nucleus at birth two days prior to the cervical overhemisection spinal injury. Both normal littermates (N = 9) and spinally injured animals (N = 12) were examined after postinjection survival periods of 10 or 22 days.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2324323 TI - Early development of retinal ganglion cell dendrites in the marsupial Setonix brachyurus, quokka. AB - The dendritic morphology of retinal ganglion cells was studied in flat-mounted retinae of the marsupial Setonix brachyurus, quokka. In the adults, horseradish peroxidase (HRP) was applied to the vitread surface of flattened retinae. Wide-, large-, medium-, and small-field classes appeared to correspond to gamma, alpha, delta, and beta cells, respectively, in the cat (Boycott and Wassle, J. Physiol. 249:397-419, 1974). To reveal the early stages of dendritic development, HRP was placed on the optic nerve of isolated eye cups from the day of birth to postnatal day (P) 63 when the area centralis is beginning to form (Dunlop and Beazley, Dev. Brain Res. 23:81-90, 1985). Youngest cells lacked dendrites and had an elongate soma in the cytoblastic layer with an endfoot contacting the ventricular surface. Once in the ganglion cell layer, the soma was rounded and dendrites appeared as short, unbranched processes. Most cells were asymmetric or "polarised" with the axon arising from the side nearest the optic disk and dendrites from the opposite side. Polarity was maintained in cells with longer, branched dendrites. A small proportion of cells exhibited a reversed polarity in which the axon arose from the side nearest the retinal edge and dendrites towards the disk. Cells appeared to acquire an approximately symmetric, adult-like tree by the addition of new primary dendrites between the existing ones and the axon hillock. Wide-, large-, medium-, and small-field cells were evident from P6, P25, P31, and P40, respectively. Spines were observed on dendrites and axons during development but were rare in the adult. Some dendro-axons were seen at all ages examined. The existence of an initial axodendritic polarity in retinal ganglion cells supports the hypothesis that the axon hillock is the determinant of dendritic geometry (Maffei and Perry, Dev. Brain Res. 41:185-194, 1988). Polarity may also contribute to the establishment of "radial orientation" in which the long axis of the elliptical dendritic tree of cells outside the area centralis points towards central retina and the weighted centre is displaced towards the retinal periphery (Leventhal and Schall, J. Comp. Neurol. 220:465-475, 1983). PMID- 2324324 TI - Candidate cell populations for respiratory chemosensitive fields in the human infant medulla. AB - The histology and location of human respiratory chemosensitive fields are not known. In contrast, the physiology of respiratory chemosensory areas in the ventral medulla of cats has been studied extensively, and their anatomy has been partially described. Using basic principles of comparative cytoarchitecture and computer-aided reconstructions of serial-sectioned medullae, we describe the histology and three-dimensional distribution of putative respiratory chemosensors in the feline and human infant medulla. We found that ventrolateral neurons of the human nucleus conterminalis are homologous to neurons identified in the feline L chemosensitive field by Trouth and others, and that ventrolaterally situated neurons in the human arcuate nucleus correspond to neurons predominating in the feline S and M fields. In addition, there are foci of thickened marginal glia along the feline ventral medullary surface that colocalize with chemosensitive fields identified by physiologic studies reported by others; we identify similar foci in the infant medulla. Thickened marginal glia are intermixed with neuronal fibers, often adjacent to neurons of the feline chemosensitive fields and their human counterparts, suggesting that they constitute a chemosensory neuropil at the medullary surface. Computer-aided reconstructions provide insight into the three-dimensional topography of putative respiratory chemosensors and their relationships to other brainstem structures in ways not obvious in single or even multiple sections. This delineation of candidate human respiratory chemosensors is a first step toward their postmortem analysis in patients with central ventilatory control disorders where finding histological abnormalities in these sites would support their role in human ventilation. PMID- 2324325 TI - Evidence for a functional and anatomical relationship between the lateral septum and the hypothalamus in the control of flank marking behavior in Golden hamsters. AB - Golden hamsters with established dominant/subordinate relationships communicate their social status by rubbing pheromone-producing flank glands against objects in the environment. This behavior, called flank marking, is controlled by vasopressin-sensitive neurons localized to the anterior hypothalamus. Vasopressinergic magnocellular neurons in the nucleus circularis and medial aspect of the supraoptic nucleus are thought to be a source of neurotransmitter for the initiation of flank marking. The present study was undertaken to examine the extrahypothalamic control of flank marking. The anatomical and functional connections between the lateral septum and the vasopressin-containing nuclear groups in and around the anterior hypothalamus were examined by: (1) tracing afferent and efferent connections following microinjection of horseradish peroxidase and Phaseolus vulgaris-leucoagglutinin into the lateral septum, and (2) recording odor-induced flank marking prior to and following ibotenate lesions in the septum. The greatest number of perikarya retrogradely labeled with horseradish peroxidase were found lateral to the anterior hypothalamus and ventral to the fornix in the area of the lateral hypothalamus. The vasopressin containing nuclear groups, e.g., paraventricular, supraoptic, suprachiasmatic nuclei, and the nucleus circularis, were devoid of labeled perikarya. Nerve terminals anterogradely labeled with Phaseolus vulgaris-leucoagglutinin were primarily localized to the anterior hypothalamus, in and around the nucleus circularis, and the medial aspect of the supraoptic nucleus. The lateral aspect of the supraoptic nucleus was devoid of nerve terminals as were the paraventricular and suprachiasmatic nuclei. The anatomical connections between the lateral septum and the hypothalamus appear to be necessary for the control of flank marking, since the microinjection of ibotenate into this limbic site significantly reduced odor-induced flank marking as compared to control microinjections of 0.9% NaCl. PMID- 2324326 TI - Migratory pathways and selective aggregation of the lateral reticular neurons in the rat embryo: a horseradish peroxidase in vitro study, with special reference to migration patterns of the precerebellar nuclei. AB - The migration and ultimate domain invasion of postmitotic lateral reticular nucleus (LRN) neurons were followed in embryonic day 15-20 (E15-E20) rat embryos, by using a horseradish peroxidase (HRP) in vitro axonal tracing method. All of the LRN axons elongate and neuronal somata migrate via the subpial or marginal migratory stream (mms), circumnavigating the ventrolateral aspect of the medulla at the glial endfeet level. They reach the ventral midline at E16, bypass it, and begin to settle in their final territory at E17. At E18 the LRN anlage is fully formed, and at E19-E20 its cells have finished their migration and are rapidly differentiating. Comparison of these sequential steps with their counterparts in the development of the inferior olive (ION) and external cuneatus (ECN) brings to light the essential role of the neuroepithelial cells of the interolivary commissure (the "floor plate"). This zone is likely to act as 1) a chemoattractant for the growth cones of the LRN, ION, and ECN, and 2) a decision making center, which instructs the somata of these neurons to cross the midline or not, ultimately governing the crossed or uncrossed pattern of their projection to their common target, the cerebellum. Finally, the ontogeny of the LRN and ECN provides a most surprising example, even unique in the central nervous system, of long-distance, neurophilic migration that conveys neuronal cell bodies contralaterally to the side on which they proliferate. PMID- 2324327 TI - Differential growth and remodelling of ganglion cell dendrites in the postnatal rabbit retina. AB - The postnatal dendritic maturation of small field type 1 (SF1), medium field type 1 (MF1) and type 2 (MF2), and large field type 1 (alpha) ganglion cells in the rabbit retina was compared qualitatively and quantitatively. Dendritic tree structure was revealed by intracellular injection of the fluorescent dye Lucifer yellow, and the stained cells were then morphologically separated on the basis of some area, dendritic field size, total dendritic length, number of nodes, and mean internodal distance. Cells in the visual streak and an area inferior to the streak were sampled from retinae between birth and adulthood. The dendrites of all studied classes of rabbit ganglion cells were extensively covered by short spine-like appendages. As in cat retina, many dendritic spines disappeared by the end of the third postnatal week, at which stage the adult dendritic form could be recognised. However, there was differential loss in the number of spines from the dendrites of the four cell classes. In both the streak and inferior retina, adult SF1 cells had the same number of spines/dendritic unit length throughout postnatal life, whereas MF1 and MF2 ganglion cells lost at least half of their number of spines/unit dendritic length by maturity. Alpha ganglion cells lost virtually all their dendritic spines by adulthood. In both retinal locations, there were small changes in the number of nodes (dendritic branch points) of small field and medium field ganglion cells but alpha cells lost between 70 to 80% of their nodes by adulthood. The dendrites of ganglion cells with contrasting morphology thus undergo differential remodelling during postnatal maturation. The completion of the period of dendritic remodelling coincided with the first appearance of adult receptive field organisation, suggesting that structural remodelling, in particular that involving dendritic spines, may be associated with the development of the cell's synaptic circuitry. The dendrites of neighbouring postnatal ganglion cells in the rabbit retina also grow by different amounts; the increase in dendritic tree area, total dendritic length, and mean internodal distances of alpha cells exceeded that of small field and medium field cells in corresponding retinal positions. This implies that retinal dendrites elongate by active growth rather than by "passive stretching." PMID- 2324328 TI - Correlation of monosynaptic field potentials evoked by single action potentials in single primary afferent axons and their bouton distributions in the dorsal horn. AB - The relationship between structure and function of the projections of single identified primary cutaneous axons was investigated by recording cord dorsum potentials at 4 sites in response to electrical stimulation of the single axon and visualizing the boutons of the axon stained by intracellular injection of horseradish peroxidase. The rostrocaudal extent of boutons differed from fiber to fiber ranging from 4.14-11.50 mm; their location in the dorsal horn also varied in agreement with the known somatotopy of the presynaptic neuropil and dorsal horn neurons. Rostrocaudal distributions of cord dorsum potentials and boutons of individual fibers revealed good agreement. Cord dorsum potential amplitude and length of the spinal projection were positively correlated with number of boutons, but no correlation with bouton density was found. The spinal projection of afferents innervating slowly adapting type 1 mechanoreceptors exhibited a greater rostrocaudal extent (mean: 8.48 mm) than those innervating rapidly adapting mechanoreceptors (i.e., hair follicle and field receptors: mean: 5.87 mm). Although the mean total number of boutons was greater for axons with slowly adapting receptors (7,250/fiber) than for axons of rapidly adapting receptors (4,677/fiber), no differences in the longitudinal density of boutons (boutons/mm) were observed. Likewise, summed amplitudes of cord dorsum potentials at the 4 recording electrodes were larger for SA1 afferents than for those of field and hair follicle afferents. A major role for the number of boutons in determining these differences is supported by the finding that the calculated average contribution per bouton to cord dorsum potentials (expressed as an amplitude coefficient a) was similar for slowly and rapidly adapting afferents. No evidence was found for regions in which boutons did not contribute to the cord dorsum potential. PMID- 2324329 TI - Dorsomedial telencephalon of lungfishes: a pallial or subpallial structure? Criteria based on histology, connectivity, and histochemistry. AB - The dorsomedial telencephalon of lepidosirenid lungfishes has been interpreted in two divergent ways: earlier investigators regarded it as a subpallial (septal) structure; more recently, it has been reinterpreted as the medial pallium (hippocampus). To resolve this question, we identified parameters that are conclusive in their association with either the medial pallium or the septum in anamniotes. The present study examines the position of ependymal thickenings and the distribution of acetylcholinesterase (AchE) in the cerebral hemispheres of the African lungfish Protopterus, the Australian lungfish Neoceratodus, and the amphibian species Xenopus and Ambystoma. In addition, projections from the hypothalamus (paraventricular organ) to the telencephalon are investigated in Protopterus. Ependymal specializations are located dorsally and ventrally in the lateral ventricles of amphibians, but laterally and medially in lungfishes. In Protopterus, the paraventricular organ projects to the medial telencephalic hemisphere, but not to the dorsal roof. High levels of AchE are present in restricted neuropil regions of the medial hemisphere and in the ventral and ventrolateral telencephalon, but they are lacking in the dorsal roof. Intensely AchE-stained neuronal cell bodies are located in the ventral telencephalon (rostrally) and the dorsomedial telencephalon (at mid-level). In Neoceratodus, AchE staining is pronounced in the septal area, but absent in the pallium. The terminal nerve proper lacks AchE stain in Protopterus; nerve fibres of the preoptic nerve are AchE-positive in both lungfish species. In Xenopus, AchE staining of fibers and terminals is restricted to the subpallium (medial septum, tuberculum olfactorium, striatum, nucleus accumbens, and medial amygdala); cell bodies are AchE positive in parts of the subpallium and rostral pallium. Comparison of cytological, histochemical, and "connectional" parameters substantiates the interpretation that the dorsomedial telencephalon of lungfishes represents a subpallial, but not a "medial pallial" structure. The dorsomedial part of the lepidosirenid telencephalon corresponds to the septum in the most plesiomorphic living lungfish, Neoceratodus forsteri, but it differs considerably from the dorsomedial telencephalon (medial pallium) in amphibians. PMID- 2324330 TI - Quantitative fine structure of capillaries in subregions of the rat subfornical organ. AB - The differentiated cytology across subregions of the rat subfornical organ (SFO) prompted our hypothesis that ultrastructural features of capillary endothelial cells would vary topographically and quantitatively within this small nucleus. We used electron microscopic and computer-based morphometric methods to assess fine structural dimensions of the capillary endothelium in four distinct subregions of the SFO from Long-Evans and homozygous Brattleboro rats. Three types of capillary were present. Type III capillaries (resembling those of endocrine glands) had an average wall thickness of 0.17 microns, 54% thinner than those of Type I and II capillaries. Pericapillary spaces around Type III capillaries measured 56 microns2, 100% larger than for Type I vessels (resembling those of skeletal muscle). Only Type III capillaries contained fenestrations (9 per microns2 of endothelial cell) and were the predominant type of capillary in central and caudal subregions of the SFO. Type I capillaries, prevalent in the transitional subregion between the central and rostral parts of the SFO, had 10 cytoplasmic vesicles per micron2 of endothelial cell area, a number not different from that of Type III capillaries but 3x the frequency found in Type II vessels. Type II capillaries (those typical of "blood-brain barrier" endothelium) had low vesicular density (3 per microns2), no fenestrations, and no pericapillary spaces. Luminal diameters and the densities of mitochondria and intercellular junctions were not different among capillary types or subregions in the SFO. Furthermore, there were no morphometric differences for any capillary dimensions between Long-Evans and Brattleboro rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324331 TI - Interspecific variation in the projection of primary afferents onto the electrosensory lateral line lobe of weakly electric teleosts: different solutions to the same mapping problem. AB - We demonstrate that preterminal axons composing the primary afferent projection onto the four somatotopically organized electrosensory lateral line lobe (ELL) segments in weakly electric gymnotiform teleosts course in fundamentally different directions in the most commonly studied species. Afferents enter the deep fiber layer (dfl) of the ELL and course in variable, but species-specific, directions within a horizontal plane before turning dorsally to terminate within the deep neuropil layer of the ELL (dnl). Among the species considered here, apteronotids exhibit the tightest projection pattern. Afferents enter the rostral ELL from the anterior lateral line nerve ganglion (ALLNG) in a nonsomatotopic fashion. As they course horizontally, these fibers undergo a rostrocaudal somatotopic sorting along the ventrolateral border of the dfl, then turn within a horizontal plane to course medially across the ELL segments. These medially coursing horizontal fibers are sorted: they form sublaminae according to the nerve branch containing their peripheral axon. Horizontal axons then turn dorsally, form fascicles, and terminate within the dnl. Within the dorsal fascicles, axons run directly into the dnl with little deviation, and their terminal fields exhibit no appreciable spread. In sternopygids, dfl horizontal fibers course in directions orthogonal to those in apteronotids. Fibers enter the rostral ELL and course medially across segments before turning caudally within segments. Unlike apteronotids, sternopygid horizontal fibers do not sort tightly by nerve branch. As horizontal axons turn dorsally they also form tight fascicles. But rather than terminating directly and without spreading, as in apteronotids, sternopygid fibers disperse from these fascicles and become sorted horizontally a second time prior to terminating in the dnl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324332 TI - Delineation of a brain nucleus: comparisons of cytochemical, hodological, and cytoarchitectural views of the song control nucleus HVc of the adult canary. AB - The present investigation used stable area-specific, neuronal properties instead of Nissl stain to delineate the boundaries of the nucleus hyperstriatalis caudal c (HVc) in the telencephalon of the adult male canary. Immunocytochemical procedures combined with retrograde tracing labeled a large population of perennial long-projecting neurons that contain estrogen receptors in the canary HVc. The HVc area defined by the distribution of these neurons was congruent with the HVc area defined in Nissl-stained sections during the breeding period. The HVc area defined in Nissl-stained preparations showed an extensive seasonal change in size, confirming previous results (Nottebohm: Science, 214:1368-1370, '81). In contrast, the HVc area defined by the distribution of the estrogen receptor containing long-projection neurons showed little or no seasonal change in size. Because these neurons are permanent, the HVc seems to be of rather constant size year round. The internal morphology of the HVc, however, undergoes seasonal alterations, which are reflected in changes in size of the HVc area distinguishable in Nissl-stained sections. The combination of cytoarchitectural criteria of Nissl-stained preparations with area-specific cytochemical and hodological markers to delineate the boundaries of a brain nucleus might give new insights in the partitioning and neuronal plasticity of brain areas. PMID- 2324333 TI - Development of the electrosensory nervous system of Eigenmannia (gymnotiformes): II. The electrosensory lateral line lobe, midbrain, and cerebellum. AB - The somatotopically and functionally organized electrosensory system of gymnotiform teleosts provides a model for the study of the formation of ordered nerve connections. This paper describes the development of the major electrosensory nuclei within the hind- and midbrain. All three main electrosensory nuclei--the electrosensory lateral line lobe (ELL), dorsal torus semicircularis (torus), and tectum--grow by adding cells at their caudolateral borders. Toral and tectal germinal zones arise from lateral ventricular outpocketings that either completely or partially close by maturity. In the ELL before day 5 postspawning, germinal cells form from an initial periventricular germinal zone, then migrate to the caudolateral border of the hindbrain and begin dividing. The ELL grows from two main germinal zones, one for the medial segment, and one for the three lateral tuberous segments. Within each ELL germinal zone, newly formed cells arise from two areas: granular cells arise from a ventral subzone, pyramidal cells are generated more dorsally. Granular cells remain in situ, whereas pyramidal cells may migrate rostromedially. Cells begin differentiating as soon as they are formed. Spherical and pyramidal cells send ascending axons into the internal plexiform layer by day 14-18 and the ELL gradually begins to assume its mature laminar appearance. The ELL grows caudally, preceding the caudal lobe of the cerebellum, which will eventually lie over and fuse with it. Primary electrosensory afferents enter the ELL by day 6; incoming afferents form four fascicles within the ELL, suggesting the formation of separate ELL segments. Unlabelled projections between labelled fields from a single nerve branch filled with HRP on day 7 suggest that somatotopic order is already present at this early age. In the periphery, receptor addition is unordered, occurring along nerve branch pathways. Meanwhile the ELL adds cells in an orderly fashion at its caudolateral border. This suggests that primary afferents shift position caudally with growth to maintain their somatotopic relationships. Because all three central nuclei are in topographic register and grow by adding cells caudally, during growth ELL efferents to the torus and toral efferents to the tectum may utilize passive mechanisms, such as fiber-fiber interactions, to guide axons. PMID- 2324334 TI - Cluster organization and response characteristics of the giant fiber pathway of the blowfly Calliphora erythrocephala. AB - Intersegmental descending neurons (DNs) link the insect brain to the thoracic ganglia. Iontophoresis of cobalt or fluorescent dyes reveals DNs as uniquely identifiable elements, the dendrites of which are situated within a characteristic region of the lateral deutocerebrum. Here we demonstrate that DNs occur as discrete groups of elements termed DN clusters (DNCs). A DNC is a characteristic combination of neurons that arises from a multiglomerular complex in which the main components of each glomerulus are a characteristic ensemble of sensory afferents. Other neurons involved in the complex are local interneurons, heterolateral interneurons that connect DNCs on both sides of the brain, and neurons originating in higher centers of the brain. We describe the structure, relationships, and projections of eight DNs that contribute to a descending neuron cluster located ventrally in the lateral deutocerebrum, an area interposed between the ventral antennal lobes and the laterally disposed optic lobes. We have named this cluster the GDNC because its most prominent member is the giant descending neuron (GDN), which plays a cardinal role in the midleg "jump" response and which is implicated in the initiation of flight. The GDN and its companion neurons receive primary mechanosensory afferents from the antennae, terminals of wide- and small-field retinotopic neurons originating in the lobula, and endings derived from sensory interneurons that originate in leg neuropil of the thoracic ganglia. We demonstrate that DNs of this cluster share morphological and functional properties. They have similar axon trajectories into the thoracic ganglia, where they invade functionally related neuropils. Neurons of the GDNC respond to identical stimulus paradigms and share similar electrophysiological characteristics. Neither the GDN nor other members of its cluster show spontaneous activity. These neurons are reluctant to respond to unimodal stimuli, but respond to specific combinations of visual and mechanosensory stimulation. These results suggest that in flies groups of morphologically similar DNs responding to context-specific environmental cues may cooperate in motor control. PMID- 2324335 TI - Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. AB - The distribution of cells that express mRNA encoding the androgen (AR) and estrogen (ER) receptors was examined in adult male and female rats by using in situ hybridization. Specific labeling appeared to be largely, if not entirely, localized to neurons. AR and ER mRNA-containing neurons were widely distributed in the rat brain, with the greatest densities of cells in the hypothalamus, and in regions of the telencephalon that provide strong inputs in the medial preoptic and ventromedial nuclei, each of which is thought to play a key role in mediating the hormonal control of copulatory behavior, as well as in the lateral septal nucleus, the medial and cortical nuclei of the amygdala, the amygdalohippocampal area, and the bed nucleus of the stria terminalis. Heavily labeled ER mRNA containing cells were found in regions known to be involved in the neural control of gonadotropin release, such as the anteroventral periventricular and the arcuate nuclei, but only a moderate density of labeling for AR mRNA was found over these nuclei. In addition, clearly labeled cells were found in regions with widespread connections throughout the brain, including the lateral hypothalamus, intralaminar thalamic nuclei, and deep layers of the cerebral cortex, suggesting that AR and ER may modulate a wide variety of neural functions. Each part of Ammon's horn contained AR mRNA-containing cells, as did both parts of the subiculum, but ER mRNA appeared to be less abundant in the hippocampal formation. Moreover, AR and ER mRNA-containing cells were also found in olfactory regions of the cortex and in both the main and accessory olfactory bulbs. AR and ER may modulate nonolfactory sensory information as well since labeled cells were found in regions involved in the central relay of somatosensory information, including the mesencephalic nucleus of the trigeminal nerve, the ventral thalamic nuclear group, and the dorsal horn of the spinal cord. Furthermore, heavily labeled AR mRNA-containing cells were found in the vestibular nuclei, the cochlear nuclei, the medial geniculate nucleus, and the nucleus of the lateral lemniscus, which suggests that androgens may alter the central relay of vestibular and auditory information as well. However, of all the regions involved in sensory processing, the heaviest labeling for AR and ER mRNA was found in areas that relay visceral sensory information such as the nucleus of the solitary tract, the area postrema, and the subfornical organ. We did not detect ER mRNA in brainstem somatic motoneurons, but clearly labeled AR mRNA-containing cells were found in motor nuclei associated with the fifth, seventh, tenth, and twelfth cranial nerves. Similarly, spinal motoneurons contained AR but not ER mRNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2324336 TI - The pathology of an inherited hyperlipoproteinaemia of cats. AB - The gross and histological features of congenital lipoprotein lipase deficiency are described in eight cats. The main histological features could be directly related to the presence of the chylomicronaemia. They consisted of lipid accumulation within clear vacuoles or ceroid accumulation within residual bodies in parenchymatous organs such as the liver, spleen, lymph nodes, kidney and adrenal gland. Xanthomata were seen in various sites, probably arising either from frank haemorrhage or the leakage of lipid-rich plasma perivascularly. As in human lipoprotein lipase deficiency there was no evidence of the formation of atherosclerotic plaques. Focal degenerative changes were, however, present within arteries and this may indicate blood vessel weakness and explain the tendency to haemorrhage and xanthomata/granulomata formation. The degeneration and fibrous replacement of glomeruli and nephrons possibly arises from pressure necrosis of adjacent xanthomata and alterations in renal blood flow. PMID- 2324337 TI - Myocardial biochemical changes in furazolidone-induced cardiomyopathy of turkeys. AB - This study tested the hypothesis that membrane transport is the major biochemical system of the myocardium altered in furazolidone-induced cardiomyopathy (round heart disease), before the development of myocardial failure, and that metabolic enzymes and contractile proteins are less affected. Compared with controls, maximal percentage depression of activities of myocardium from furazolidone treated birds were 40 for creatine kinase, 30 for glycolysis, 30 for glycogen, 20 for myofibrils, 20 for Krebs's cycle enzymes, 15 for fatty acid oxidation and 10 for total soluble protein. Sodium and potassium transport, antioxidant system activity, myosin, myosin isoenzyme patterns and amino acid aminotransferases were unaffected. In marked contrast, the calcium-transport ATPase activity of the sarcoplasmic reticulum had undergone a 60 per cent compensatory increase in activity. The pattern of biochemical changes observed is consistent with a role of ischaemia in the pathogenesis of round heart disease and indicates that calcium transport by the sarcoplasmic reticulum is the major biochemical system affected. PMID- 2324338 TI - The effect of recent vaccination on the dose-response to experimental Dermatophilus congolensis infection in rabbits. AB - Dermatophilus congolensis infection of rabbits was used to investigate the effects of active immunity on epidermal challenge following vaccination. Rabbits (three groups of four) were vaccinated intradermally with live whole-cell preparations of D. congolensis strains SS18C and FD11 (groups SSVAC and FDVAC respectively); a third group (UNVAC) remained as unvaccinated controls. Two weeks after vaccination, separate 1.5-cm2 clipped and ether-swabbed skin sites were inoculated with a 10-fold dilution range (10(7) to 10(1) zoospores per cm2 of skin) of SS18C or FD11. Lesion scores at each site were calculated from the sum of individual scores (0 to 4+) for erythema, oedema and scab formation multiplied by the percentage of the inoculated area affected. A clear dose-response relationship between the size of inoculum and the severity of lesions was seen for both D. congolensis stains in the control group (UNVAC). In the SSVAC and FDVAC groups the lesions were less severe and developed more quickly. The number of zoospores required to cause infection in the vaccinated animals was up to 10,000-fold higher for homologous inoculated sites and 100-fold for heterologous sites. Serological analysis was carried out with an ELISA system. Vaccination and challenge resulted in increases in specific antibody against D. congolensis antigens. Cross-reacting antibody to the heterologous strain of D. congolensis used was demonstrated in both vaccinated groups but did not correlate with equal protection to homologous or heterologous challenge. The dose-response relationship demonstrated by this model enabled semi-quantitative analysis of the effects of vaccination on D. congolensis infective dose and severity of infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324339 TI - Clinical neurology and brain histopathology in NZB/NZW F1 lupus mice. AB - Active generalized systemic lupus erythematosus (SLE), clinical neurological deficits and histological lesions in the brains were present in New Zealand Black/New Zealand White (NZB/W) F1 mice at 10 to 18 months of age. Clinical neurological abnormalities of the central nervous system (CNS) were detected with a standardized neurological examination and scoring procedure. Active generalized SLE was present in all mice of this group, as determined by elevated serum anti DNA antibodies and by the presence of glomerulonephritis. High titres of serum anti-cardiolipin antibodies were present in almost all mice. On histopathological examination, most of the brains had prominent mononuclear cell infiltration around cerebral and hippocampal blood vessels and in the choroid plexus. A subgroup of these mice, having higher clinical neurological scores, had correspondingly higher brain histopathological scores. The neurological and histological abnormalities were compatible with a diagnosis of CNS SLE. In contrast, 2-month-old NZB/W, 5-month-old C57Bl/6 and 14-month-old C57Bl/6 mice had low neurological scores, low serum anti-DNA antibody titres, low or absent anti-cardiolipin antibodies and no evidence of brain or kidney pathological lesions. PMID- 2324340 TI - Glycogen accumulation in the renal tubular cells of spontaneously occurring diabetic WBN/Kob rats. AB - Cytoplasmic and nuclear accumulation of glycogen granules in the kidney cells of 72 male WBN/Kob rats with a long-term diabetic condition was studied histologically and by electron microscopy. The incidence and degree of the accumulation showed good correlation with the blood glucose concentration. In the kidneys, there was evidence of two types of lesion, cytoplasmic glycogen accumulation in the distal convoluted tubules and nuclear accumulation in the ascending thick segment of Henle's loops. Electron microscopically, the cytoplasmic glycogen accumulation was often associated with an increased number of lysosomal bodies containing lamellar bodies. Glycogen bodies, the halo of which was thought to be identical with that of nuclear bodies, were frequently observed in the nuclei containing the glycogen granules. These morphological and topographical differences between the two types of lesion were considered suggestive of different pathogenetic mechanisms for glycogen accumulation in the kidney cells. PMID- 2324341 TI - Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities in normal canine mammary gland and in mammary tumours and their correlation with oestrogen receptors. AB - Glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phosphogluconate dehydrogenase (6-PGD) activities were studied in 10 normal canine mammary glands and in 19 canine mammary tumours, which included seven benign and 12 malignant neoplasms. The malignant tumours were also examined for oestradiol receptors. The mean G-6 PD and 6-PGD activities were 5.17 +/- 1.84 and 1.65 +/- 0.64 IU per g protein in normal glands, 8.8 +/- 2.7 and 3.8 +/- 0.99 IU per g protein in benign and 19.6 +/- 5.2 and 8.5 +/- 2.1 IU per g protein in malignant mammary tumours. The enzyme activities were significantly higher in tumour tissue than in normal glands. Malignant tumours had much greater activity than benign. With the increasing anaplasia, there was a corresponding rise in the activity of the two enzymes. There was an inverse correlation between the oestrogen receptor (ER) status and the enzyme activity. The ER-positive tumours had low and ER-negative tumours had high enzyme activities. PMID- 2324342 TI - Experimental acute selenium intoxication in lambs. AB - The toxic effects of 5 mg per kg body weight of selenium given as sodium selenite orally or parenterally to growing lambs were examined. There was considerable individual variation in both susceptibility to intoxication and the degree of pathological change displayed. The results affirm the previously reported deleterious effects on the cardiovascular, respiratory and urinary systems and highlight damage to secondary lymphoid tissue in various organs. The use of a histochemical method for detecting selenium bonds demonstrated correlation between the density of reaction-product and histopathological changes within tissues, and showed the distribution of selenium in other tissues in which the gross and histopathological findings were non-specific or minimal. PMID- 2324343 TI - The effect of inoculation of coagulase-negative staphylococci into the ovine mammary gland. AB - In each of two experiments, the effect of inoculation of coagulase-negative staphylococci (C-NS) into the ovine mammary gland was studied. In the first experiment, ewes were inoculated with one of six different C-NS to study differences in the pathogenicity of the isolates. In the second, ewes were inoculated with Staphylococcus simulans to study the sequential histopathological features of the infection. The existence of subclinical mastitis was established by consistent isolation of bacteria, the demonstration of high somatic cell counts in milk and an inflammatory reaction in biopsy samples of mammary tissue. A variation in the pathogenicity of the different isolates was evident: one Staph. chromogenes isolate caused clinical mastitis, four Staph. simulans isolates caused subclinical mastitis and one Staph. xylosus isolate caused a transient increase of somatic cell counts. Neutrophilic infiltration was the predominant histopathological finding. Lysis of neutrophils, destruction of alveoli and, in late stages of the infection, infiltration of lymphocytes and fibrous tissue proliferation were also noted. PMID- 2324344 TI - Observations on the pathogenesis of Chlamydia psittaci infection of pregnant sheep. AB - Susceptible pregnant sheep were infected with Chlamydia psittaci at different stages of early and mid-gestation. Placentas and foetuses were examined by microbiological, serological, histopathological and immunochemical methods at various intervals thereafter. While ewes were susceptible to infection from early gestation onwards and infections of placentas and foetuses occurred from about 60 days gestation (dg), pathological changes were not detected until after 90 dg. These changes consisted of initial rapid replication of C. psittaci in the trophoblast at the limbus of the placentomal hilus, leading to local necrosis and contiguous spread of infection to involve the cotyledonary and intercotyledonary placenta and apposing endometrium. Foetal pathology consisted of focal necrosis in liver and other organs suggestive of embolic dissemination of infection from the placenta. An early foetal immune response was detected including the demonstration of IgM and IgG antibody to C. psittaci and quantitative evidence of a B cell response to infection. Pathogenetic mechanisms are discussed. PMID- 2324345 TI - Melanotic hamartoma of the hind brain in a riding horse. AB - A 3 1/2-year-old bay gelding of the cob type showed nervous signs and coughing associated with breaking-in and exercise. At post-mortem examination, heavy melanin pigmentation of the meninges of the hind brain and the medulla was identified and, on histological examination, melanin-containing cells were found within connective tissue extending into the medulla. The lesion was considered to be a melanotic hamartoma. PMID- 2324346 TI - Retinal cysts in the eye of the Asian musk shrew, Suncus murinus, (Mammalia, Insectivora). AB - The development of retinal cysts in the eye primordia of Suncus murinus embryos was studied. Retinal infoldings were first identified in the 17.5-day-old embryo (crown rump length--CRL = 6.3 mm). At this time, the apex of the developing retinal fold could be identified attached to the lens. The pigmented epithelium did not take part in the formation of the cyst. The retinal fold closed, to form a cyst, by day 23 of embryonic development (CRL = 14.0 mm). The newly formed retinal cyst remained continuous with the retina and extended toward the lens where it attached to the lens epithelium. Retinal cysts had an oval, bilaterally symmetrical shape and a narrow lumen, which, lined by the internal limiting membrane, occasionally contained cellular debris. The dimensions of the cysts were usually 100 to 150 microns (diameter) by 200 to 250 microns (length). Retinal cysts appeared in 45 per cent of the embryos examined. PMID- 2324347 TI - Cyclopolymerizable monomers for use in dental resin composites. AB - The simple reaction of conventional monofunctional acrylate monomers with paraformaldehyde has yielded a new class of difunctional monomers. The unique proximity of the double bonds within these compounds allows a facile cyclopolymerization to incorporate a cyclic ether structure into the polymer backbone. The external position of the acrylate esters means that these pendant groups can be varied for alteration of the physical properties of the monomers and the corresponding polymers. A series of the new monomers has been prepared and polymerized under dilute solution and bulk conditions to yield non crosslinked and crosslinked polymers, respectively. The polymers exhibited high degrees of conversion and significantly reduced polymerization shrinkage, compared with polymers obtained from conventional diacrylate or dimethacrylate monomers. These properties appear to be a direct result of an efficient cyclopolymerization process. The combination of improved conversion to polymer with less contraction makes these monomers ideal candidates for use in dental resin composites. A preliminary evaluation of their potential in this application has shown that with suitable ester functionality, they can be formulated to provide composites with excellent mechanical strength properties. PMID- 2324348 TI - The relationship between composition and properties of posterior resin composites. AB - The effects of filler concentration and resinous components on the properties of highly filled composites were determined for prediction of the durability of the restorative resins. Resinous components of seven proprietary light-cured posterior resin composites were extracted by chloroform solvent and examined by the Fourier Transform Infrared (FTIR) method. Filler concentration was determined by the thermogravimetric method. Diametral tensile strength, Knoop hardness, and Barcol hardness tests for the composite, as well as extracted resinous matrix, were performed by standard experimental procedures. Toothbrush abrasion test of the resin composites was evaluated by a toothbrushing machine giving the equivalent of five years' toothbrushing and examined with a roughness meter. The degree of conversion of resin composites ranged from 43.5 to 73.8%. The volume fraction of filler varied from 58.2% to 74.2%. The ranges of diametral tensile strength and Knoop and Barcol hardness numbers obtained were 39.8 MPa to 60.0 MPa, 41.8 to 81.9, and 76.3 to 89.2, respectively. Significant correlations (p less than 0.01) were obtained between filler fraction and diametral tensile strength (r = 0.89, S.E. = 3.66) and between filler fraction and Knoop hardness number (r = 0.89, S.E. = 8.39). The increase in strength with increased filler concentration might be related to filler/matrix bonding. PMID- 2324349 TI - The effect of plaque thickness on progression of artificial caries lesion formation in situ. AB - Eighty thin enamel sections with artificially-formed caries lesions were implanted in the buccal surfaces of molars (in the removable partial dentures of ten subjects) and covered with a steel mesh for plaque accumulation to occur. The mesh was placed in contact with the enamel surface in half the lesions and 0.5 mm above the lesions in the other half, thus facilitating formation of thin and thick plaque samples. Following two-week use of a non-fluoride dentifrice, the lesions were analyzed for mineral change by quantitative microradiography. Significant mineral was lost from lesions in both groups, but the loss was twice as large in the thick-plaque group. These findings are important to in vivo remineralization models, since they show that plaque thickness should be controlled for minimization of variation. PMID- 2324350 TI - Effect of dietary components on the indigenous oral bacterial flora of BALB/c mice. AB - Diet is recognized as one of the most important factors affecting the equilibrium of the oral bacterial flora. Studies related to dental caries development have focused mainly on the effect of carbohydrates. In the present work, using swabbing coupled with an immuno-colony-blot assay, we followed the indigenous oral bacterial populations of BALB/c mice fed diets with different concentrations of sucrose, starch, proteins, lipids, vitamins, and minerals for a period of 14 days. The results indicate that although high-sucrose diet favored an increase of the proportion of S. faecalis, only variations in the protein and the starch concentrations significantly influenced the composition of the indigenous oral bacterial populations of BALB/c mice. With low-protein diets, the proportion of Lactobacillus murinus decreased, that of Streptococcus faecalis increased, while that of Staphylococcus aureus was relatively stable. A diet containing a high proportion of starch (65%) resulted in a significant increase in the population of S. faecalis, while that of S. aureus decreased proportionally. With the same diets used as in vitro culture media, growth of L. murinus was the fastest at high protein concentrations, while that of S. faecalis was not affected by the protein concentrations. These results indicate a direct effect of dietary protein content on the indigenous oral bacterial populations of BALB/c mice. PMID- 2324351 TI - Serum antibody response to antigens of oral gram-negative bacteria by cats with plasma cell gingivitis-pharyngitis. AB - The etiology of a form of periodontal disease in domestic cats known as plasma cell gingivitis-pharyngitis is not understood. Actinobacillus actinomycetemcomitans and Bacteroides species have been strongly implicated as the cause of periodontitis in humans and other mammalian species, and most affected patients manifest serum antibodies reactive with the infecting bacteria. We and others have isolated Bacteroides species from the oral flora of cats. Using enzyme-linked immunosorbent assay (ELISA) and immunoblot procedures, we measured serum antibodies in affected and control cats reactive with human isolates of A. actinomycetemcomitans, B. gingivalis, and B. intermedius, and purified lipopolysaccharide (LPS) from these and other species, and Bacteroides of cat origin. Affected cats had serum antibody titers reactive with these Gram negative anaerobic bacteria that were significantly elevated relative to those of normal control cats. The quantitatively major antigens recognized by cat serum antibodies are proteins; this contrasts sharply with serum antibodies from humans with juvenile periodontitis, where LPS is the quantitatively major antigen fraction. Our data support the idea that plasma cell gingivitis-pharyngitis in cats may have a bacterial etiology, and that Gram-negative anaerobes similar to those that cause periodontitis in humans and other mammals may be involved. PMID- 2324352 TI - Endocytosis in odontoclasts and osteoclasts using microperoxidase as a tracer. AB - Microperoxidase (MP, a peptide tracer) was intravenously injected into rats after six days of tooth movement by the Waldo method. Bone resorption was seen along the distal bone surface of the inter-radicular septum of the upper first molar, and tooth root resorption occurred along the mesial and distal surfaces of the distal root of the same molar. Odontoclasts were smaller in size and numbers than osteoclasts, but had the same organelles [multiple nuclei, ruffled borders (RB), clear zones, vacuoles, mitochondria, and specific granules] as osteoclasts. MP was deposited on the resorbed area through the clear zone and was transported into the vacuoles along the channels of the RB. The uptake of MP by odontoclasts was small, compared with that by osteoclasts. Collagen fibrils were found in the channels of the RB but were not detected in the vacuoles. Instead, filament-like structures were seen in the vacuoles and were located very near the collagen fibrils in the channels. Fibroblasts outside the resorbed lacunae had endocytosed collagen. In contrast, some cells close to odontoclasts (osteoclasts) in the dentin (bone)-resorbed lacunae had not endocytosed any collagen fibrils. These findings suggest (1) that odontoclasts resorb the dentin or cementum just as osteoclasts do in bone resorption, (2) that the resorbed area connects with the extracellular spaces of the odontoclasts or osteoclasts, and (3) that the organic components (e.g., collagen fibrils) of dentin or cementum are endocytosed through the channels of the RB in the same manner as that for MP. However, the endocytotic ability of odontoclasts appears inferior to that of osteoclasts. PMID- 2324353 TI - Evaluation of alveolar bone in relation to nutritional status during pregnancy. AB - Demand for nutrients necessary for the formation of mineralized tissues increases dramatically during pregnancy to meet fetal requirements. The purpose of this clinical study was to identify short-term effects of pregnancy and dietary intakes of calcium, phosphorus, protein, and vitamin C on radiographic density and alveolar crest morphology of the mandible. Seventy-six subjects between ten and 20 weeks' gestational age were recruited from the Jefferson County, Alabama, Department of Health maternity clinic. Initially, an evaluation of their diet was done, and a single periapical radiograph was taken in the canine-premolar region of the mandible. A final evaluation of the diet and a periapical radiograph of the same teeth were obtained at a time as close to the expected date of delivery as possible. Dietary evaluation consisted of a 24-hour recall history and a food frequency history at the two visits. Radiographs were made with a bite-block film holding system with occlusal registration in acrylic for reproduction of projection geometry at the two visits. An aluminum stepwedge was incorporated for densitometric standardization. Measurements of plaque, and bleeding and pocket depth probing were recorded for control of local effects on alveolar change. Standard statistical procedures of regression determined correlation of 12 nutrients and periodontal variables with bone density change and with alveolar crest morphology change. Vitamin C intakes (24-hour recall) showed a positive correlation (p = 0.033) with bone density change, and calcium intakes (24-hour recall) showed a negative, but not significant, correlation (p = 0.058) with bone density change, contributed particularly by subjects with the highest calcium intakes. The strongest relation with alveolar crest morphology change was the interproximal pocket-depth change (p = 0.086). PMID- 2324355 TI - Jaw muscle activity in relation to the direction and point of application of bite force. AB - This study examined the way the masseter and the anterior and posterior temporal muscles of human subjects were activated when a bite force of constant magnitude was exerted at different teeth in different defined directions. Subjects were instructed to produce a bite force of a particular magnitude (250 N) and direction (vertical, anterior, lateral, posterior, or medial) using a three component force transducer and a feedback method. Simultaneously, the EMG activity of the muscles was registered with use of surface electrodes. Unilateral bite forces were produced at the right canine, second premolar, and second molar. In addition, a bilateral vertical premolar bite was examined for comparison of activity levels of the muscles of both sides. The results showed that, on average, the activities of the right and left side muscles did not differ in a bilateral vertical bite. Moreover, in a unilateral vertical bite, there were no significant right-left differences. For all bite force directions, more muscle activity was required for production of a constant bite force at the anterior side of the dental arch than at the posterior side. An exception to this rule was the activity of the posterior temporal muscle in a posteriorly directed bite. There was a close relationship between the direction of bite force and jaw muscle activity. Variations in activity were small for the anterior temporal muscle and large for the posterior temporal and masseter muscles. All muscles that were studied were always active, even in directions in which they could be expected to act antagonistically. PMID- 2324354 TI - Release of organic matrix components from bovine incisor roots during in vitro lesion formation. AB - The solubilization of organic matrix components during demineralization of powdered and intact root sections from adult bovine incisors was investigated. Root powder was demineralized with 0.1 mol/L acetic acid, pH 4.0, at 4 degrees C and 37 degrees C. Surfaces of intact root sections were subjected to 0.1 mol/L acetic acid, pH 4.0 (for production of erosive lesions), or to 0.1 mol/L lactic acid, 0.2 mmol/L methane hydroxy diphosphonate, pH 5.0 (for production of subsurface lesions at 37 degrees C). The solubilized organic material was analyzed for collagen, total noncollagenous protein (NCP), organic phosphate (Po), and proteoglycans (PGs), which were measured as chondroitin 4-sulfate (C-4 S). For root powder, a maximal release of NCPs and PGs was found only after neutralization of the extraction mixture. For both temperatures tested, the average amounts of liberated noncollagenous components (NCCs) were the same, i.e., 0.68 micrograms [NCP - Po], 0.11 microns Po, and 0.10 micrograms C-4-S per mumols released calcium. The amino acid composition of the NCP fraction revealed relatively high amounts of aspartic acid and serine. These findings indicate that the NCCs were easily liberated from the tissue, and that the NCP fraction consisted mainly of phosphoprotein. Demineralization of intact root sections resulted in average amounts of solubilized NCCs of 0.21 micrograms [NCP - Po], less than 0.01 micrograms Po, and less than 0.01 micrograms C-4-S per mumols released calcium, independent of incubation time and lesion type. The amino acid composition of all NCP fractions was virtually the same, high in glutamic acid, but lower in aspartic acid and serine when compared with the neutralized powder extracts. For both demineralization solutions, the amounts of solubilized collagen were 0.07 and 0.16 micrograms per micromol released calcium after three and 28 days of incubation, respectively. Our experiments indicate that phosphoprotein and proteoglycans may be released from root surfaces during the periods of neutral pH that follow acid demineralization. PMID- 2324356 TI - Depressed eruption rate of the rat maxillary incisor in a drug-induced uncompensated hemolytic state model. AB - Female rats weighing about 180 g were separated into two groups. One group (A) received phenylhydrazine (PHZ) every other day during three weeks (for induction of an uncompensated hemolytic state), while the control group (C) received saline. The evidence for the establishment of the uncompensated hemolytic state was obtained by hematocrit value, reticulocyte count, and red-cell-volume-59Fe uptake. Body-weight gain (which is a measure of overall body growth rate), body length gain (which is a measure of longitudinal skeletal growth rate), food intake, and maxillary incisor eruption rate (ER) were significantly depressed in rats of group A during the PHZ-injection period, in relation to rats of group C. These results indicate that anemia and/or associated factors depress ER, along with body growth and skeletal growth. PMID- 2324357 TI - Properties of alkaline phosphatase of the human dental pulp. AB - Enzymatic and immunological properties of alkaline phosphatase [ALP; orthophosphoric monoester phosphohydrolase, alkaline optimum, EC 3.1.3.1.] in the human dental pulp were investigated. In inhibition and thermal inactivation studies, dental pulp ALP showed properties of universal-type ALP (kidney/bone/liver type). Dental pulp ALP cross-reacted with polyclonal and monoclonal antibodies against purified swine-kidney ALP, and with monoclonal antibody against ALP of human osteoblast-like cells in the same manner as ALPs of human bone and kidney. The sodium dodecyl sulfate-gel electrophoretic pattern showed a 140,000-Mr native protein band. These data suggest that dental pulp ALP can be classified as a universal-type ALP having antigenic determinants common to ALP of the kidney and bone. PMID- 2324358 TI - Research and progress of oral and maxillofacial surgery in the People's Republic of China. PMID- 2324359 TI - Trends in quality assurance in the dental profession. AB - I have dealt with three questions concerning trends in quality assurance. In summary, we must ask ourselves whether the profession can develop methods for dealing effectively with dentists whose performance is found to be continually unsatisfactory. This may be achieved by making available effective tools for others to use in developing quality assurance systems. These tools will involve criteria and standards for services, appropriateness of treatment, measuring outcomes of care, and methods for assessing dental practices. This may involve working closely with consumer representatives to assist in gaining the consumer's point of view and incorporating it into the technology of quality assurance. Berwick, in a recent article in the New England Journal of Medicine, called for the application of a "Theory of Continuous Improvement" rather than the "Theory of Bad Apples." His view is that we should examine the process itself and try to improve it rather than look for outliers or bad apples. His point of view is consistent with the concept of quality assurance I have been talking about. Quality assurance systems should assure quality by proper assessment, identifying strengths and weaknesses in the provision of care. The strengths should be reinforced and the weaknesses should be rectified. This necessitates positive communication between those who perform quality assurance and those who are being evaluated. It also assumes that the technology is appropriate, recommendations are reasonable and that, when changes are made, quality will improve. In order to make the theory of continuous improvement work, it should be consistent with financial incentives and professional values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324360 TI - Quality assurance: one school's response. PMID- 2324361 TI - Quality assurance in a school of dentistry: getting started. PMID- 2324362 TI - Where is quality assurance going in dental school curricula? PMID- 2324363 TI - Effect of financial incentive on productivity in a postgraduate general dentistry program. PMID- 2324364 TI - Self-perceived needs for faculty development at Canadian dental schools. PMID- 2324365 TI - A comparison of in-service teaching methods on clinic aspesis for dental personnel. PMID- 2324366 TI - Assessment of factors related to faculty attrition in dental technology education. PMID- 2324367 TI - Recruiting college students as patients via a pre-paid preventive dental health plan. PMID- 2324369 TI - Resolution of pain associated with varicose and telangiectatic leg veins after compression sclerotherapy. AB - Many patients presenting for treatment of superficial varicosities and telangiectasias on the legs are seeking relief of pain or discomfort in addition to cosmetic improvement. Of 215 sclerotherapy patients, 114 (53%) complained of various painful symptoms involving areas of telangiectasias (vessels 0.1-1 mm in diameter) and varicosities (vessels greater than 1 mm in diameter). In order to determine whether sclerotherapy is effective in reducing leg pain and discomfort, hundreds of patients receiving two or more treatment sessions of compression sclerotherapy with hypertonic saline were surveyed for the pretreatment and post treatment presence of numerous symptoms associated with telangiectasias and varicosities of the leg. For all symptoms combined, the overall reported relief of pain was 85% (p less than 0.001). Side effects from the treatment were minimal. These results indicate that sclerotherapy for telangiectasias and varicosities is not only a cosmetic procedure but a safe and valuable medical therapeutic modality, highly effective in relieving leg pain and discomfort. PMID- 2324368 TI - Compression in the treatment of leg telangiectasia: a preliminary report. AB - The use of postsclerotherapy compression was evaluated in 37 women with bilaterally symmetrical telangiectatic leg veins. Compressed vessels tended to achieve a greater clinical resolution when located on the distal leg and/or when greater than 0.5 mm in diameter. Postsclerotherapy hyperpigmentation fell from 40.5% to 28.5% with the use of compression. In addition, ankle and calf edema were lessened if a graduated compression stocking was worn immediately after sclerotherapy. PMID- 2324370 TI - Pulsed-dye laser treatment of leg telangiectasia: with and without simultaneous sclerotherapy. AB - Thirty consecutive female patients with red leg telangiectasia less than 0.2 mm in diameter were treated with a Candela SPTL-1 Pulsed Dye Laser (PDL) tuned to 585 nm with a pulse duration of 450 microseconds at energies ranging from 6.0 to 8.5 J/cm2 delivered through a 5-mm spot size to the entire length of the telangiectasia. Seven patients with 25 patches of telangiectatic matting after previous sclerotherapy were also treated. Twenty-seven patients with symmetrical telangiectatic patches or a large "starburst" telangiectatic flair that could be divided into two separate treatment sites were treated at one site with PDL alone, and at the other site with a combination of PDL followed immediately by sclerotherapy (SCL) with Polidocanol 0.1-0.25 ml per injection site at a concentration of either 0.25%, 0.5%, or 0.75%. PDL treatment is efficacious for both essential telangiectasia and vessels that arise through the phenomena of telangiectatic matting. Sixty-five percent of vessels are completely faded with treatment. PDL alone has a remarkably low incidence of adverse sequelae. Treatment is most efficacious if all vessels larger than 0.2 mm in diameter, especially varicose and reticular feeding veins, are treated first. Treatment results are not affected by vessel location. And post-treatment compression of this type of vessel appears unnecessary. Combination PDL/SCL treatment appears to offer no advantage to sclerotherapy treatment alone and has a significant degree of complications when treatment is limited to red telangiectasia less than 0.2 mm in diameter with the laser parameters utilized. PMID- 2324371 TI - The use of meshed advancement flaps in the treatment of lesions of the lower leg. AB - We describe the use of meshed local advancement flaps to repair surgical defects of the lower leg. The procedure produces a lattice of small cutaneous defects that heal rapidly by second intention. The technique is simple to perform and is suitable for large defects of the lower leg. Only minimal supervision is required post-operatively, and the wound causes virtually no pain. PMID- 2324372 TI - The principle of cosmetic junctions as applied to reconstruction of defects following Mohs surgery. AB - Reconstruction of defects that cross several cosmetic units can be aesthetically accomplished by preserving the integrity of the cosmetic boundaries using multiple grafts and flaps rather than one all-emcompassing repair. PMID- 2324373 TI - Cryohydrodissection in cervicofacial rhytidectomy. PMID- 2324374 TI - Use of live pigs in postgraduate surgical training. PMID- 2324375 TI - Immunogenicity of injectable collagen implants. PMID- 2324376 TI - Influence of insecticide treatment on German cockroach (Dictyoptera: Blattellidae) movement and dispersal within apartments. AB - Two similar studies were done to investigate effects of insecticide treatments on German cockroach, Blattella germanica (L.), movement and dispersal within individual units in multifamily housing. In the first study, Whitmire PT-565 Pyrethrum Insect Fogger (pyrethrins), Diazinon 4E (diazinon), Protector (permethrin), and Baygon 1.5 (propoxur) did not induce any significant changes in cockroach distribution, and rates of movement within apartments decreased. In the second study, populations treated with sublethal doses of pyrethrins and resmethrin settled to their original distribution 24 h after treatment. Results from both studies indicate that thorough insecticide applications do not significantly affect German cockroach population dispersal or movement patterns within apartments. PMID- 2324377 TI - Topical and oral toxicity of sulfluramid, a delayed-action insecticide, against the German cockroach (Dictyoptera: Blattellidae). AB - The LD50 of sulfluramid topically applied to 2-d-old, fifth instars of the German cockroach, Blattella germanica (L.), was estimated at 14.5 micrograms/g (95% FL = 13.7-15.4 micrograms/g). Sulfluramid was significantly more toxic than topically applied hydramethylnon (LD50 = 29.2 [19.0-46.5] micrograms/g). Sulfluramid had delayed toxicity but caused mortality significantly faster than hydramethylnon after topical application. The oral LD50 against newly enclosed, fifth instars was estimated to be 4.1 (3.9-4.4) micrograms/g; this toxicity was significantly greater than when sulfluramid was topically applied. Mortality caused by sulfluramid occurred significantly more slowly in the dietary exposures than in the topical applications. Sulfluramid at 1,000 ppm in diets was not a feeding deterrent to nymphal B. germanica. PMID- 2324378 TI - Genetics of organophosphate resistance in field populations of the house fly (Diptera: Muscidae). AB - The genetics of resistance to the organophosphate insecticide diazinon were investigated in four populations of the house fly, Musca domestica L., collected in the southern United States. Crosses were made between individual females of lines derived from each population and males of a susceptible strain with three recessive mutants on chromosome II. Individual F1 females were crossed to mutant males, and the progenies were scored for resistance to diazinon and for the presence of mutant phenotypes. A major chromosome II gene for resistance to diazinon was present in all populations at an overall frequency of 83%. Map distances between the resistance gene and the mutant aristapedia and between the mutants aristapedia and stubby wing were highly variable in all populations. Recombination among the visible mutants was usually reduced in resistant progenies relative to susceptible progenies. The data suggest that a single major gene for resistance to diazinon was present on chromosome II in all test populations at variable map positions and is usually associated with a chromosome rearrangement, probably an inversion. The results are similar to those obtained earlier with house fly populations selected for resistance to insecticides in the laboratory; therefore, they seem to be characteristic of field and laboratory populations of the house fly. Overall, the data offer an explanation for previous results suggesting the existence of multiple, closely linked genes for metabolic resistance to insecticides on house fly chromosome II. PMID- 2324380 TI - ET nurses as the specialists in the care and prevention of incontinence. PMID- 2324379 TI - Fly pupae as attractant carriers for toxic baits for red imported fire ants (Hymenoptera: Formicidae). AB - Eight laboratory-reared ant species were fed baits of house fly, Musca domestica L., pupae treated with hydramethylnon. Two fire ant species, Solenopsis invicta Buren and Solenopsis geminata (F.), and Pheidole morrissi (Forel) were killed; average percentage of mortality of the five other species was less than 20%. In contrast, all species that were fed the commercial fire ant bait containing hydramethylnon (Amdro) died or were adversely affected. In the field, applications of house fly pupae and eye gnat, Hippelates pusio Loew, pupae dipped in acetone solutions of fenoxycarb significantly reduced population indices of the red imported fire ant, S. invicta, compared with commercial formulations of fenoxycarb (Logic) and hydramethylnon (Amdro). Field observations showed that the pupae of either species can be carried or moved by one or two worker ants. The smooth, hard cuticle of the pupae make them easy to handle and apply with application equipment. The current cost of house fly pupae is considerably more than the cost of a granular carrier, pregel defatted corn grits. However, if mass production methods reduce this price differential, fly pupae could become an effective and more species-specific fire ant bait carrier. PMID- 2324381 TI - Introduction for theme issue on urinary incontinence. PMID- 2324382 TI - Urinary incontinence: challenge for collaboration in care. PMID- 2324383 TI - A practical approach to teaching self-catheterization to children with myelomeningocele. PMID- 2324384 TI - Stress urinary incontinence in women. PMID- 2324385 TI - Kegel exercises enhanced by biofeedback. AB - New motor learning is dependent on sensory feedback, both visual and kinesthetic. Many factors may function to offset the effectiveness of Kegel exercises. These factors include (1) faulty feedback generated by substituting muscles, (2) insufficient kinesthetic feedback produced by the low intensity contraction of the weakened pelvic floor, and (3) absent or impaired sensation that limits the sensory cues that normally trigger a motor response or reflex that prevents incontinence. Because biofeedback can compensate for the loss of sensation, its comprehensive application can be an invaluable tool in the retraining of bowel and bladder control, especially where function is lost through trauma, neurologic injury or long term disuse/misuse. As such, biofeedback can enhance the many behavioral interventions developed to decrease incontinence, including Kegel exercises. PMID- 2324386 TI - Managing incontinence in the nursing home population. PMID- 2324387 TI - Helping caregivers cope: managing urinary incontinence associated with Alzheimer's disease. PMID- 2324388 TI - Application of the articulation index to the speech recognition of normal and impaired listeners wearing hearing protection. AB - The present study examined the application of the articulation index (AI) as a predictor of the speech-recognition performance of normal and hearing-impaired listeners with and without hearing protection. The speech-recognition scores of 12 normal and 12 hearing-impaired subjects were measured for a wide range of conditions designed to be representative of those in the workplace. Conditions included testing in quiet, in two types of background noise (white versus speech spectrum), at three signal-to-noise ratios (+ 5, 0, - 5 dB), and in three conditions of protection (unprotected, earplugs, earmuffs). The mean results for all 21 listening conditions and both groups of subjects were accurately described by the AI. Moreover, a single transfer-function relating performance to the AI could describe all the data from both groups. PMID- 2324389 TI - A generalized approach to random noise synthesis: theory and computer simulation. AB - A generalized approach to the synthesis of Gaussian and non-Gaussian random noises as well as purely impulsive waveforms having a preselected amplitude spectrum has been developed. The basic idea behind the synthesis is to construct the amplitude-time waveform from the frequency domain, i.e., from the amplitude and phase spectra. By maintaining a predetermined (reference) amplitude spectrum and performing certain specific manipulations of the phase spectrum within any selected band of frequencies and then applying the inverse discrete Fourier transform (IDFT), peaks in the non-Gaussian random waveform can be constructed from the selected band of frequencies that have been phase manipulated. Entire families of signals can thus be produced having the same energy spectrum, but statistical characteristics that vary along the continuum from Gaussian (skewness = 0 and kurtosis = 3) through non-Gaussian (variable skewness, kurtosis, and crest factor) to purely impulsive (shock/transient) signals. The theoretical background and the results of a series of numerical simulations will be presented which demonstrate the functional relation between various phase spectrum manipulations and the descriptors of the synthesized random noise. The results show that the approach is viable and that the synthesized random waveforms can be easily tailored to simulate a variety of real-world acoustic/vibration signals, e.g., high kurtosis (impulsive) industrial noises, helicopter noises, missile vibrational signals, etc. PMID- 2324390 TI - Estimation of eardrum acoustic pressure and of ear canal length from remote points in the canal. AB - Sound pressure distributions in the human ear canal, whether unoccluded or occluded with ear molds, were studied using a probe tube technique. On average, for frequencies below 6 kHz, the measuring probe tube had to be placed within 8 mm of the vertical plane containing the top of the eardrum (TOD), determined optically, in order to obtain sound pressure magnitudes within 6 dB of "eardrum pressure." To obtain that accuracy in all of the eight subjects studied, the probe had to be within 6 mm of the TOD. Since probe location relative to the drum has to be known, a purely acoustic method was developed which can be conveniently used to localize the probe-tip position, utilizing the standing wave property of the sound pressure in the ear canal. The acoustically estimated "drum location" generally lay between the optically determined vertical planes containing the TOD and the umbo. On average, the "drum location" fell 1 mm medial to the TOD. Of the 32 estimates made acoustically in various occluded and unoccluded conditions in 14 subjects, 30 estimates lay within a +/- 2-mm range of this average. PMID- 2324391 TI - Auditory nonlinearities measured with auditory-evoked potentials. AB - This article describes the use of auditory-evoked potentials (AEPs) as a tool to assess nonlinear processes in the auditory system. Two-tone signals were used as stimuli to obtain AEPs in both animal and human subjects. Frequency analysis of the physiologic waveforms revealed frequencies in the evoked potential that were not present in the acoustic signal. The largest distortion product in the evoked potential corresponded to the difference between the two primary frequencies (f2 f1). This distortion product was present in all subjects tested. Other distortion products at frequencies defined by n(f2-f1), where n less than 5, were also present in some individuals. These frequencies represent distortion components generated from an even-order nonlinear system. Extensive acoustic and electric calibration procedures provided substantial evidence that the distortion products recorded in the AEP were biologic in origin and not the result of acoustic or recording artifact. PMID- 2324392 TI - Intensity discrimination as the driving force for loudness. Application to pure tones in quiet. AB - Loudness functions and their associated neural-count functions are derived for steady-state tones at 250 and 1000 Hz from measurements of intensity discrimination obtained under gated and continuous conditions. The calculations are based on a multichannel generalization of the McGill-Goldberg counting model [J. Acoust. Soc. Am. 44, 576-581 (1968)]. Using the data for just noticeable differences (jnd) in intensity as input, the generalized version gives an integral relation between the neural-count function N(x) and the intensity-jnd function, where x = I/I0 and I0 is the reference intensity. Loudness functions are generated through the prescription L(x) = AN(x)--B. To determine how the detailed shapes of the intensity-jnd functions affect the form of the loudness function within the model, integration was performed over the intensity-jnd functions with and without a power-function approximation. Over a range of intensity levels from 20-95 dB, the best agreement between the calculated and measured loudness functions is obtained from the unaltered intensity-jnd functions. Consistent with psychophysical evidence and several models of intensity coding, the results predict that the output of the whole auditory nerve is unnecessary to maintain the large dynamic range observed for loudness and intensity discrimination. PMID- 2324393 TI - Upward spread of masking, hearing loss, and speech recognition in young and elderly listeners. AB - Upward spreading of masking, measured in terms of absolute masked threshold, is greater in hearing-impaired listeners than in listeners with normal hearing. The purpose of this study was to make further observations on upward-masked thresholds and speech recognition in noise in elderly listeners. Two age groups were used: One group consisted of listeners who were more than 60 years old, and the second group consisted of listeners who were less than 36 years old. Both groups had listeners with normal hearing as well as listeners with mild to moderate sensorineural loss. The masking paradigm consisted of a continuous low pass-filtered (1000-Hz) noise, which was mixed with the output of a self tracking, sweep-frequency Bekesy audiometer. Thresholds were measured in quiet and with maskers at 70 and 90 dB SPL. The upward-masked thresholds were similar for young and elderly hearing-impaired listeners. A few elderly listeners had lower upward-masked thresholds compared with the young control group; however, their on-frequency masked thresholds were nearly identical to the control group. A significant correlation was found between upward-masked thresholds and the Speech Perception in Noise (SPIN) test in elderly listeners. PMID- 2324394 TI - The effect of signal-frequency uncertainty on comodulation masking release. AB - The aim of this study was to examine whether the scheme of across-frequency comparison underlying comodulation masking release (CMR) is sensitive to the placement of the signal in the array of comodulating bands. This was addressed using the paradigm of signal-frequency uncertainty. In the first experiment, maskers were constructed of linearly spaced sinusoidally amplitude-modulated tones, and the signal was a pure tone presented at one of five frequencies. A small uncertainty effect was observed for the noncomodulated masker, but no significant effect was observed for the comodulated masker. In the second experiment, the maskers were constructed of logarithmically spaced noise bands, and the signal was a pure tone presented at one of seven frequencies. In these conditions, an uncertainty effect was observed in both noncomodulated and comodulated maskers, which was larger than that observed in experiment 1. The results were interpreted as indicating that the mechanism of across-frequency comparison underlying CMR is sensitive to signal location. PMID- 2324395 TI - Unification of perturbation measures in speech signals. AB - Voice perturbation measures, formerly defined in a somewhat ad hoc fashion, are discussed within the framework of signal theory. An attempt is made to unify a variety of existing jitter, shimmer, and noise measures on the basis of common underlying perturbation functions and their derivatives. Some simple modulations (sinusoid, Gaussian noise, linear trend) are imposed on cyclic parameters in phonation (e.g., amplitude and fundamental frequency) to test the ability of perturbation measures to detect or reject these types of modulations. It is expected that this systematic approach to perturbation analysis will be helpful in identifying the sources of irregularity in the voice and, thereby, in the detection of laryngeal disorders. PMID- 2324396 TI - Contraction and relaxation-induced oscillations of the left ventricle of the heart during the isovolumic phases. AB - A theoretical analysis is presented for the transient dynamical response of the left ventricle of the heart during the isovolumic contraction and relaxation phases of the cardiac cycle. Small oscillations of the left ventricular cavity pressure and wall motion are excited by the initial rates of filling and emptying of the ventricle as well as the rate of change in muscle fiber activation. The analysis applies to the genesis of the first and second heart sounds. The ventricle is modeled as a finite, thick-walled incompressible cylinder having a continuum of imbedded axial and circumferential active muscle fibers, which interacts with a fixed volume of an incompressible, ideal fluid. The solution is obtained using a two-timing asymptotic expansion procedure. The theoretical calculations of left ventricular pressure waveforms compare favorably with published recorded pressure waveforms. The amplitude spectra of computed waveforms contain information concerning the active elastic modulus of the fibers, which is a measure of cardiac contractility. PMID- 2324397 TI - Intermodulation distortion in the cochlea as shown by offset action potential (AP) masking curves. AB - In their recent article "Offset AP masker tuning curve and the FFT of the stimulus" [J. Acoust. Soc. Am. 84, 1354-1362 (1988)], Henry and Lewis demonstrated that the tuning curve obtained by the simultaneous masking of the whole nerve action potential (AP) could have two tips when the AP is generated at the offset of the envelope of a high-level probe. The primary tip falls below the probe frequency, whereas the secondary tip falls above the probe frequency. Curves obtained for the onset response with either forward or simultaneous masking did not show the secondary peak, nor did curves obtained for the offset response with forward masking. Henry and Lewis discussed various reasons for the secondary tip, but came to no conclusion as to the underlying mechanisms. Here, it is reasoned that the secondary tip of the offset curve can be simply explained by the generation within the cochlea of intermodulation distortion (IMD), which acts as a forward masker to the offset response. The IMD is dominated by the cubic component (2f1-f2) and arises from the interaction of the probe tone and the simultaneous masker. Finally, it is reasoned that the lower sideband of the frequency splatter present at probe offset is the primary stimulus for the evoked neural response under probe offset conditions. Thus the offset curve will always have a primary tip that is lower in frequency than that of the respective onset curve. These hypotheses are supported by single-fiber data. PMID- 2324398 TI - On the use of adaptive procedures in binaural experiments. AB - Adaptive psychophysical procedures have been routinely used in monaural experiments for many years, but only sparsely used in binaural experiments. In this letter, (1) the increasing use of adaptive procedures in binaural experiments is documented; (2) factors that determine their appropriateness are discussed; and (3) data that attest to their usefulness are presented. PMID- 2324399 TI - Negatively biased recall in children with self-reported symptoms of depression. AB - This study investigated differences in depressed and nondepressed children's recall of positively and negatively reinforced behavior. Twenty-six children with self-reported symptoms of depression in the fourth through sixth grades were compared with a matched sample of 26 nondepressed children to determine if there was a negative bias in depressed children's recall. Subjects first generated guesses of the most common associations to each of a series of 40 words. Later, when compared with their nondepressed peers, the children with depressive symptomology were less accurate in recalling which words they had answered correctly and remembered fewer of their own correct responses. They also did more poorly when asked to recall the correct answers that had been provided by the investigator. The two groups did not differ, however, in their recall of which items had been answered incorrectly or in their recall of their previous wrong responses. These results suggest that children with self-reported depressive symptomology do not remember negative experiences more than do nondepressed children; rather, they recall positive experiences less well. Selective forgetting of positively reinforced behavior could be a serious handicap for depressed children in school. It could also play an important role in the maintenance and perhaps even the etiology of depressive symptomatology in children. PMID- 2324400 TI - Comorbidity of ADHD and reading disability among clinic-referred children. AB - Of a consecutive series of 115 boys diagnosed in a university outpatient clinic as ADHD, 39% also demonstrated a specific reading disability. Pure ADHD patients were compared with mixed ADHD + RD and normal controls on a battery of cognitive and attentional measures. The aim was to determine whether a distinct pattern of deficits would distinguish the groups. Both ADHD subgroups performed significantly worse than controls on measures of sequential memory and attentional tasks involving impulse control and planful organization. Only ADHD + RD boys differed from controls on measures or rapid word naming and vocabulary. The results are discussed within the framework of an automatic versus effortful information-processing model. PMID- 2324401 TI - The Revised Behavior Problem Checklist and severely emotionally disturbed adolescents: relationship to intelligence, academic achievement, and sociometric ratings. AB - This study explored the relationship among the subscales of the Revised Behavior Problem Checklist and intelligence, academic achievement, and sociometric ratings for a sample of 62 severely emotionally disturbed adolescents enrolled in a special school. A relationship of the Attention Problems-Immaturity subscale with intelligence scores and mathematics achievement was found. Four of six subscales were found to be related to peer sociometric ratings of social acceptance, while only one subscale was related to sociometric ratings of peer acceptance of his/her classmates. These findings are discussed within the context of previous research. PMID- 2324402 TI - Attributional style in aggressive adolescent boys. AB - Past research suggests that aggressive children misattribute hostile intentions to peers during ambiguous provocative interactions. This study sought to extend the analysis of attributional differences between aggressive and nonaggressive boys to a sample of court-involved adolescents and their perceptions of interactions involving both peers and adults. Three groups of youngsters (nonoffenders, nonaggressive offenders, and aggressive offenders) participated in a structured interview and provided causal attributions for interpersonal problems commonly faced by teenagers. Results indicated that offenders were more likely than nonoffenders to attribute blame to others in ambiguous problem situations. Among offenders, external, person-centered blame attributions were significantly related to aggressiveness. This relationship was found only in ambiguous situations, and the correlation between such person-centered attributions and aggressiveness was higher in adult-oriented interactions than in peer-oriented ones. Overall, the results suggest that aggressiveness among offenders is associated with an attributional style that is characterized by the tendency to attribute blame for problems in ambiguous interactions to global, dispositional characteristics of others. PMID- 2324403 TI - Depressive symptoms in Swedish adolescents. AB - This study examined the prevalence of self-reported depressive symptoms in a Swedish urban school sample (n = 547) aged 13 to 18 years using the Beck Depression Inventory (BDI). The data obtained were examined with respect to sex and age differences and compared with a clinical sample of adolescents hospitalized because of psychiatric disturbances. The results indicated a strong preponderance of depressive symptoms among girls in the school sample, in particular for the severe symptom level. Eight percent of subjects reported depressive symptoms sufficiently high to be classified as a moderate, and 2% as a severe, level of depression. Factor analysis yielded four factors representing dysphoric mood, social activity, relationship, and food-related dimensions. The BDI showed a high internal consistency, and test-retest reliability calculated for a 2-week and a 2-month interval revealed strong correlations. The means of total scores on the BDI for the clinical sample were significantly higher than for those in the school sample. PMID- 2324404 TI - Dentists: satisfaction and attitudes on the future. PMID- 2324405 TI - Adult orthodontic services. Review of the role of the orthodontist and orthodontic services in providing care to the older patient. PMID- 2324406 TI - What does the college do? PMID- 2324407 TI - Professionalism and ethics. PMID- 2324408 TI - Protective measures in dental treatment. PMID- 2324409 TI - The effect of inhaled fenoterol, administered during the late asthmatic reaction to house dust mite (Dermatophagoides pteronyssinus). AB - A double-blind, placebo-controlled crossover study was set up to investigate the effect of fenoterol (400 micrograms) during the late asthmatic reaction (LAR). Twenty young subjects with asthma (mean age, 11.8 years; range, 8.3 to 20.6 years) were selected on the basis that they developed an LAR after bronchial challenge with Dermatophagoides pteronyssinus. After the LAR occurred, a placebo and fenoterol were administered blindly by a metered-dose inhaler, with an interval of 15 minutes and in alternating, random sequence. At the start of the study, that is, a documented LAR, the two groups of subjects had the same severity of LAR, as expressed by the fall of the FEV1 (mean, -34.5% versus 33.5%). The mean FEV1 of the 10 patients who received placebo first changed only 1.1% (+/- 5.0), whereas after fenoterol, The FEV1 increased by 20.7% (+/- 10.8). In the 10 patients receiving fenoterol first, the mean FEV1 rose by 18.8% (+/- 8.0), whereas the placebo inhalation resulted in a supplementary increase of 3.1% (+/- 7.0). The paired Student's t test between these differences (placebo versus fenoterol) was highly significant (p less than 0.001). Although it was demonstrated in some studies that beta-agonists did not prevent the LAR, the present study demonstrates that the administration of fenoterol can reverse the FEV1 significantly, although it was not reversed completely, during an allergen induced LAR. PMID- 2324410 TI - Rose hips: a new occupational allergen. AB - We evaluated 13 workers with respiratory symptoms apparently related to occupational exposure to powdered rose hips. Nine workers had asthma, five had rhinitis, and one worker had urticaria. Seven workers had evidence of IgE specific for rose hips based on positive skin prick tests and positive in vitro tests. Four workers with histories suggestive of asthma related to work exposure underwent bronchopulmonary challenges with rose hips, and two workers had positive challenges with greater than 20% declines in FEV1 measurements. We conclude that rose hips are occupational allergens capable of producing asthma. PMID- 2324411 TI - Venom immunotherapy in the Hymenoptera-allergic pregnant patient. AB - Natural or iatrogenic causes of anaphylaxis are significant risk factors in pregnancy. A 3% to 5% risk of sting anaphylaxis in any pregnant woman with insect sting allergy untreated with venom immunotherapy (VIT) can be calculated. Insect sting anaphylaxis has allegedly caused severe fetal abnormalities and is a potential cause of fetal loss and severe maternal morbidity and/or mortality. Hymenoptera anaphylaxis is a highly preventable cause of anaphylaxis, but VIT may itself carry a risk potential, with an appropriate 5% reaction during buildup and 1% reaction risk during maintenance VIT. To assess the safety of VIT in pregnancy, we have gathered data from 26 women with 43 pregnancies. All the women were receiving VIT. One woman was stung early in pregnancy with anaphylaxis resulting. Outcome of pregnancy was normal. Thirty-six of the pregnancies ended normally. There were two mild adverse reactions to VIT, neither of which required treatment. One child was born with multiple congenital abnormalities of unknown cause. Since congenital malformations may occur as frequently as one in 40 live births, these data do not suggest a significant increased risk from VIT during pregnancy. PMID- 2324412 TI - Imported fire ant (IFA) sensitivity: IFA-specific levels of serum IgG and IgG4. AB - Imported fire ant (IFA) whole body extract (WBE) and venom (V)-specific IgG and IgG4 antibodies and specific IgE antibodies were evaluated in sera from 56 IFA sensitive individuals (18 undergoing immunotherapy with IFAWBE and 38 individuals not being treated) and 44 nonatopic and atopic control subjects with no history of IFA allergy. Although there was no difference in the level of IFAWBE- or IFAV specific IgG between treated and untreated patients, both groups had higher levels of IFAWBE- and IFAV-specific IgG (p less than 0.05) than did control subjects. Patients receiving treatment tended to have higher levels of IFAWBE specific IgG4 than did either untreated patients (0.05 less than p less than 0.10) or control subjects (p less than 0.05). Levels of IFAV-specific IgG4 were higher in treated patients than in control subjects (p less than 0.05) but were not different between treated and untreated patients. Levels of IFAWBE- and IFAV specific IgE antibodies did not differ between the two patient populations but were higher in both groups than in control subjects (p less than 0.05). The ratio of IgG4 to IgE (G4/E) for both IFAWBE and IFAV was calculated for all groups. The ratios of IFAWBE- and IFAV-specific G4/E were higher in treated patients and in control subjects as compared to nontreated patients (p less than 0.05). IFAV specific G4/E ratios were lower in treated patients than in control subjects, but IFAWBE-specific G4/E ratios were the same as ratios for control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324413 TI - Migratory responses of eosinophil and neutrophil granulocytes from patients with asthma. AB - In the present study the migratory function of eosinophil and neutrophil granulocytes from patients with asthma were investigated. Fifty-seven patients with asthmatic disease of varying severity were included. Eosinophil and neutrophil chemotactic responses to 5% pooled normal human serum (NHS), 5% allergen-challenge serum, 2.5% zymosan-activated serum, N-formyl-methionyl-leucyl phenylalanine (10 nmol/L), chemokinetic responses to albumin (2 gm/L) and 5% NHS, and the eosinophil and neutrophil chemotactic and chemokinetic activities of serum were investigated. Eosinophils from patients with asthma demonstrated significantly (p less than 0.02) increased chemotactic responses to allergen challenge serum, zymosan-activated serum, and N-formyl-methionyl-leucyl phenylalanine, compared with eosinophils from references. The chemokinetic responses to albumin and NHS were increased (p less than 0.01) by eosinophils from the patients who had blood eosinophilia (greater than 400 X 10(6)/L). Sera from the patients with asthma demonstrated raised eosinophil chemotactic activity (p less than 0.001) and raised eosinophil and neutrophil chemokinetic activity (p less than 0.001). The eosinophil chemokinetic activity of serum was correlated to the relative peak expiratory flow rate of the patients (r = -0.43; p less than 0.02). The increased migratory responses were specific for the eosinophils, since the migratory responses of their neutrophils were not altered compared with that of the references. These results suggest that the eosinophils from the patients with asthma had been exposed to a priming mechanism in vivo. PMID- 2324414 TI - Immunologic and clinical status of blood donors with subnormal levels of IgG2. AB - To determine the immunologic and clinical status of individuals from a general population with subnormal levels of IgG2, we prospectively studied 37 of 312 blood donors with low IgG2 levels identified among 8015 donors. We examined (1) G2m(23) allotypes, (2) levels of other IgG subclasses and immunoglobulin classes, (3) composition of peripheral leukocyte populations, (4) responses to two carbohydrate antigen vaccines, (5) in vitro secretion of IgG subclasses by isolated lymphocytes after mitogen stimulation, and (6) clinical histories. We found that most (90%) individuals with subnormal IgG2 levels had G2m(23)- allotypes, whereas only 30% of the unselected donors had G2m(23)-. When individuals were separated according to their G2m(23) allotype, we found that IgG2 "normal" range for individuals with G2m(23)- allotype is 35% lower than for individuals with G2m(23)+ allotype. Individuals who had G2m(23)- allotype and had IgG2 levels greater than or equal to 0.8 but less than 1.3 gm/L had no other immunologic abnormalities. In contrast, the individuals with G2m(23)+ allotype and with IgG2 levels less than 1.3 gm/L and the individuals with G2m(23)- allotype and with IgG2 levels less than 0.8 gm/L often had additional immunologic abnormalities, including IgA and/or IgG4 deficiency and decreased in vitro expression of IgG2 subclass. None of these individuals had a clinical history remarkable for recurrent infections. Thus, subnormal IgG2 levels interpreted with G2m(23) corrected normal ranges may be a marker of other immunologic abnormalities but taken alone probably have little clinical significance in a general healthy population. PMID- 2324415 TI - Identification and partial characterization of the soybean-dust allergens involved in the Barcelona asthma epidemic. AB - Asthma epidemics in Barcelona, Spain, have been attributed to dust generated by the unloading of soybeans in the harbor. Sera of four different groups of 10 subjects in each group were studied: (1) patients attending an emergency room in Barcelona for an asthma attack on epidemic days, group A, (2) patients attending an emergency room for an attack on nonepidemic days, group B, (3) patients with asthma from other cities, group C, and (4) patients without asthma from Barcelona matched by age and sex with group A, group D. All subjects in group A had IgE to allergens in extracts of various soybean samples. In contrast, only one of the 10 subjects in each of groups B and C and none of those subjects in group D had IgE to uncleaned bean and hull extracts. Radioimmunoassay demonstrated that in sera from patients with asthma during an asthma outbreak reacted primarily to soybean hull and dust extracts. Sodium dodecyl sulfate-polyacrylamide and gel electrophoresis thin-layer isoelectrofocusing demonstrated protein bands of 97.4 to less than 14.4 kd and isoelectric point between 6 and 3.5. By Western blot and thin layer isoelectrofocusing/blotted radioimmunoisoelectrofocusing, IgE of patients with asthma during an asthma outbreak reacted weakly to two protein bands of molecular weight ranging from 42 to 21 kd, strongly to glycoprotein bands with molecular weight less than 14.4 kd, and isoelectric point less than 6, which appeared to be the major allergens. PMID- 2324416 TI - Occupational asthma caused by guar gum. AB - Some vegetable gums have been reported to cause asthma. We describe three subjects who were exposed at work to guar gum, which is derived from the outer part of Cyanopsis tetragonolobus, a vegetable that grows in India. The first subject worked for a pharmaceutical company; the second and third subjects worked at a carpet-manufacturing plant. All three subjects developed symptoms of rhinitis and asthma after the onset of exposure to guar gum. All subjects were atopic and demonstrated mild bronchial hyperresponsiveness to inhaled histamine at the time they were observed. Skin prick tests demonstrated an immediate skin reaction to guar gum. All three subjects had high levels of serum IgE antibodies to guar gum. Specific inhalation challenges in which the three subjects were exposed for short intervals (less than or equal to 4 minutes) to powder of guar gum elicited isolated immediate bronchospastic reactions in two subjects and a dual reaction in the other subject. PMID- 2324417 TI - Atopy in infancy predicts the severity of bronchial hyperresponsiveness in later childhood. AB - We have prospectively followed 52 children of atopic parents from birth to age 7 years, documenting clinical atopic disease and allergen skin test reactions. We found bronchial hyperresponsiveness (BHR) to histamine in 13 (25%) of the children at 7 years of age with 25 (48%) being atopic on skin testing and 15 (29%) having current wheeze, whereas 30 children (58%) had wheezed at some time during this period. BHR was significantly associated with wheeze and atopy at 5 and 7 years of age, but not during infancy. The six children with moderate to severe BHR (provocative dose causing a 20% fall in FEV1 less than 0.8 mumol) formed a distinct subgroup with significantly more wheeze and atopy both during infancy and at 5 years of age when these children were compared to children with milder degrees of BHR. The group with moderate to severe BHR also differed significantly from the nonhistamine-reactive group, whereas children with milder degrees of BHR were not significantly different. We conclude that subjects most likely to develop the more severe degrees of BHR during later childhood are children who manifest atopy in infancy. PMID- 2324418 TI - Fruit allergy: demonstration of IgE antibodies to a 30 kd protein present in several fruits. AB - A patient who had experienced allergic responses to various fruits developed an acute anaphylactic reaction after the ingestion of a local strain of cling peaches. The patient's serum, but not control sera, contained IgE antibodies reactive to extracts from peaches, guavas, bananas, mandarins, and strawberries in an ELISA. The patient's serum, however, did not demonstrate elevated levels of IgE antibodies to extracts from apples, pears, and nectarines. Adsorption of the patient's serum with extracts from peaches, strawberries, and mandarins resulted in a decline of detectable IgE antibodies to these fruits. Adsorption with extracts from apples and pears had no such effect. These results demonstrate the specificity of the patient's IgE antibodies to selected fruits only. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting revealed a 30 kda of protein that was recognized by the IgE antibodies in the patient's serum. This protein was not present in extracts from pears or apples. Our results highlight the importance of specific allergens in considering acute allergic reactions to individuals exhibiting sensitivity to various foods or fruits. PMID- 2324419 TI - Cogan's syndrome. PMID- 2324420 TI - Ketotifen and systemic mastocytosis. PMID- 2324421 TI - Bronchial hyperreactivity and cough induced by angiotensin-converting enzyme inhibitor therapy. PMID- 2324422 TI - Pollinosis in Brazil: changing concepts. PMID- 2324423 TI - Peripheral nerve pathways to neurons in the guinea pig inferior mesenteric ganglion determined electrophysiologically after chronic nerve section. AB - Peripheral synaptic pathways to neurons in the guinea pig inferior mesenteric ganglion (IMG) were studied. Nerve trunks innervating neurons in the ganglion were surgically sectioned and intracellular electrical responses to nerve stimulation were measured 6-8 days after surgery. In all animals ganglia were decentralized by removal of the lumbar sympathetic chain ganglia L2 through L4 and in addition two peripheral nerves were sectioned leaving the ganglion innervated by only one peripheral nerve. Fast and slow excitatory postsynaptic potential (EPSP) were evoked with electrical stimulation of each of the nerve trunks and with distension of the colon. The thresholds to evoke fast EPSPs and the amplitude of slow EPSPs were compared for each nerve trunk among the different surgical groups including sham-operated controls and completely denervated ganglia. Both fast and slow EPSPs could be evoked electrically from each intact peripheral nerve trunk after the other three nerve trunks had been sectioned, which demonstrates that nerve fibers with cell bodies in the regions innervated by the peripheral nerves make functional synaptic connections with neurons in the inferior mesenteric ganglion. In general, nerve sections increased the threshold for evoking fast EPSPs and decreased the amplitude of electrically evoked slow EPSPs compared to control ganglia. Synaptic potentials could also be evoked with stimulation of cut nerve trunks, demonstrating that branches of nerve fibers from peripheral nerves enter other nerve trunks. The hypogastric nerve was unique in that branches of axons eliciting fast but not slow synaptic potentials in the ganglion entered this nerve trunk. Distension-induced fast and slow EPSPs were present only if the lumbar colonic nerve was intact and they were not altered by section of the other nerve trunks. In contrast, the slow EPSPs evoked with electrical stimulation of the lumbar colonic nerve were significantly smaller when at least one other nerve trunk was sectioned suggesting that the axon branches from other nerve trunks which enter the lumbar colonic nerve are not activated by distension. These studies demonstrate that neurons eliciting either fast or slow synaptic potentials with cell bodies in regions innervated by the peripheral nerve trunks make functional synaptic connections with neurons of the inferior mesenteric ganglion. The results also suggest that the majority of mechanosensory neurons mediating excitatory synaptic responses to colon distension are neurons with a peripheral cell body. PMID- 2324424 TI - Reflex effects on renal nerve activity and renal vascular tone during occlusion of superior mesenteric artery in anesthetized dogs. AB - This study was designed to evaluate the contribution of the systemic baroreceptor reflex on renal nerve activity (RNA) and renal vascular resistance (RVR) during occlusion of the superior mesenteric artery (SMAO) in anesthetized dogs. Animals were divided into two groups; RVR evaluated group and RNA measured group. For evaluation of changes in RVR, the left kidney was perfused at a constant flow with heparinized blood by using a pulsatile roller pump. Renal perfusion pressure, arterial blood pressure and heart rate were measured simultaneously. During SMAO, MAP and RVR increased significantly in animals with intact systemic baroreceptors. After combined denervation of the carotid sinus and vagal nerves, a significant enhancement of this RVR response during SMAO occurred and the level of changes in RVR were significantly greater than those in animals with an intact neuraxis. In the RNA measured group, renal sympathetic nerve activity, arterial blood pressure and heart rate were measured simultaneously before and during SMAO. During SMAO, MAP and RNA increased significantly in animals with intact systemic baroreceptors. These MAP and RNA responses to SMAO were significantly enhanced in animals with combined denervation of the carotid sinus and vagal nerves. These results indicate that SMAO evokes an increase in arterial blood pressure, renal sympathetic nerve activity and renal vascular resistance. The reflex increase in renal nerve activity and renal vascular tone during SMAO is modified and minimized by an activation of systemic baroreceptors. PMID- 2324425 TI - Dietary sodium loading elevates blood pressure in baroreceptor denervated rats. AB - We have examined the possibility that defective baroreflex function may contribute to the hypertensive effect of a high dietary sodium intake. In a preliminary study we found that, after interrupting the baroreflex by sino-aortic denervation (SAD), feeding a high-sodium diet to normotensive Wistar/Kyoto rats (WKY) caused their tail-cuff blood pressure to rise to hypertensive levels. In the present study, SAD and sham-operated WKY were fed diets with either a low or a high sodium content. An increase in the sensitivity of blood pressure to sodium after baroreceptor denervation was confirmed by direct measurement of mean arterial pressure (MAP) in conscious rats via indwelling aortic catheters. After 8 weeks the MAP in SAD rats on the high sodium diet was 35 mm Hg higher than in SAD rats on the low sodium diet. Ganglion blockade reduced MAP to a similar level in all treatment groups, but pressor responses to phenylephrine were greater in SAD rats on the high sodium diet, suggesting that the hypertensive effect of sodium in this group might have been due to increased sympathetic vasoconstriction. PMID- 2324426 TI - Vagal motor neurons innervating the stomach are site-specifically organized in the dorsal motor nucleus of the vagus nerve in rats. AB - The aim of the present study was to examine the neuroanatomical relationship between the brainstem and the stomach. For this purpose, by means of a horseradish peroxidase retrograde method, we identified the distribution of individual parasympathetic preganglionic neurons projecting to three specific gastric regions that have structural and functional differences in the rat stomach. Preganglionic neurons innervating the ventral forestomach were mainly distributed in the lateral part of the left dorsal motor nucleus of the vagus nerve, while those innervating both ventral corpus and antrum were chiefly located in the medial part of the left dorsal motor nucleus. On the other hand, preganglionic neurons projecting to the dorsal forestomach and the dorsal corpus and antrum were predominantly observed in the lateral and the medial part of the right dorsal motor nucleus, respectively. These results suggest that parasympathetic preganglionic neurons innervating the stomach are site specifically organized in the dorsal motor nuclei. PMID- 2324427 TI - Extracellular calcium ions are required for muscarine-sensitive potassium current in bullfrog sympathetic neurons. AB - Cultured bullfrog sympathetic neurons were voltage-clamped in the whole-cell configuration. The extracellular medium contained tetrodotoxin (3 microM) and cesium (1 mM) to block and inward sodium current and a hyperpolarization activated cation current Attempts were made to separate the M-current from four other potassium currents. Tetraethylammonium (30 mM) was used to block a classical delayed rectifier current (IK) and a fast calcium-activated current (IC). Apamin (30 nM) was used to block a slow calcium-activated current (IAHP). 4 Aminopyridine (1 mM) was used to reduce the amplitude of a transient current (IA). In these conditions, the maximum M-conductance near 0 mV was reduced by as much as 90% when divalent cations such as cobalt (1 mM) were added to the superfusate. The maximum M-conductance was also reduced by as much as 60% when calcium ions were removed from the superfusate. The half-activation voltage in the steady-state activation curve and the reversal potential of the M-current were not significantly changed in the calcium-free solution. It is suggested that the presence of calcium ions in the extracellular space is required for the M current activation. PMID- 2324428 TI - Conjugation and deamination of circulating dopamine: relationship between sulfated and free dopamine in man. AB - In order to assess the importance of conjugation in dopamine metabolism, we infused dopamine (20 nmol/kg/min, 1 h) to seven male subjects, then measured the kinetics of free and conjugated dopamine and DOPAC (deaminated dopamine) in plasma both during and after the infusion. Dopamine increased as early as 2 min after the start of the infusion, then reached a plateau and remained elevated on a level of 25 times the basal value. Dopamine sulfate and DOPAC followed very similar patterns and increased continuously from the 30th and 20th min, respectively, until the end of the infusion (5.18- and 5.76-fold, respectively), but only dopamine sulfate remained elevated (1.65-fold) on the first day following infusion. DOPAC glucuronide increased moderately (2.58-fold) at the end of the experiment, but neither dopamine glucuronide nor DOPAC sulfate were increased despite high precursor circulating levels. Free DOPAC and dopamine sulfate levels during infusion were correlated with dopamine levels when all subjects were pooled. In addition, within a subject dopamine sulfate to dopamine correlations were found with slopes varying in a range of 1 to 15. Our results show that sulfation is significantly involved in the metabolism of circulating dopamine and is not easily saturated, suggesting that dopamine sulfate may be an index of endogenous dopamine release. PMID- 2324429 TI - Comparison of central versus peripheral nerve pathways to the guinea pig inferior mesenteric ganglion determined electrophysiologically after chronic nerve section. AB - The contributions of central versus peripheral nerve pathways to neurons of the inferior mesenteric ganglion of guinea pigs were studied. Nerve trunks innervating neurons in the ganglion were surgically sectioned and intracellular electrical responses to nerve stimulation were measured 6-8 days after surgery. Guinea pigs were divided into two experimental groups: (1) those that had the lumbar sympathetic chain ganglia (LSG) L2 through L4 removed and (2) those that had the intermesenteric, lumbar colonic and hypogastric nerves sectioned leaving central connections intact. After 6-8 days fast excitatory postsynaptic potentials (EPSPs) and slow EPSPs were recorded intracellularly in randomly selected principal ganglionic neurons. The threshold stimulus voltage to elicit a fast EPSP, the amplitude of the slow EPSP and the number of neurons in which each type of synaptic potential occurred in response to stimulation of each of the nerve trunks was compared between surgically-sectioned animals and sham-operated controls. Neither section of preganglionic nerve trunks nor of postganglionic nerve trunks eliminated all synaptic input to neurons in the ganglion, indicating that neurons with cell bodies located central to the ganglion as well as in visceral target organs made synaptic connections in the ganglion. Both fast and slow synaptic potentials could be evoked by stimulation of postganglionic nerve trunks even after they were sectioned provided that preganglionic nerves were intact, indicating that axons of central origin which synapse in the ganglion may continue out into postganglionic nerve trunks. In like manner, evidence was obtained indicating that fibers from peripheral nerve trunks which initiate either fast or slow synaptic potentials in ganglionic neurons may continue out into the lumbar splanchnic nerves. These studies demonstrate that the synaptic potentials recorded in the inferior mesenteric ganglion arise not only from neurons with cell bodies central to the ganglion but also from neurons with cell bodies located in the visceral organs which this ganglion subserves. PMID- 2324430 TI - Promise and problems in reminiscence research. AB - Nurses use reminiscence as an intervention with elderly clients to meet a wide variety of needs. Research on reminiscence has provided some support for benefits of reminiscence in maintaining or improving mood, cognitive functioning, life satisfaction, and self-esteem in the elderly. Weaknesses in reminiscence research have been presented along with suggestions for developing a body of knowledge for nursing regarding reminiscence. PMID- 2324431 TI - Frequent fallers. Leading groups to identify psychological factors. AB - CNAs might be good leaders for groups of frequent fallers for several reasons, two of which are that they provide hands-on care and they know the residents well. Residents who fall frequently do not see themselves as persons who fall; they slip, trip, or slide. Single fallers explore ways to prevent another fall. Residents attempting to "do for themselves" and thus maintain their highly-prized independence is a factor contributing to falls. Preservation of autonomy and self esteem are co-factors. Denial and independence in the faller need to be identified, supported as strengths, and incorporated into a resident's plan of care. PMID- 2324432 TI - Bladder dysfunction after a stroke--it's not always inevitable. AB - Bladder dysfunction frequently accompanies a stroke but, with appropriate management, is not necessarily a permanent deficit. Voiding problems most often experienced after a stroke include urgency, frequency, incontinence, and urinary retention. A clamping routine prior to indwelling urinary catheter removal did not affect the incidence of voiding dysfunction after a stroke. Checking consecutive post-voided residual urine volumes after a stroke is indicated to evaluate the effectiveness of bladder emptying; intermittent sterile catheterization is recommended if there is a problem. PMID- 2324433 TI - Elderly women and stress. Does marriage make a difference? AB - Although studies of gender differences in the stress/health relationship of elderly persons have been done, few have examined the combined affect of marital status and gender on health. The experience of stress may affect elderly married women differently than elderly unmarried women. The purpose of this study was to explore the differential effects of stress on elderly married women and to identify interventions that could be used in gerontological nursing practice to promote effective coping. Roy's theory is used to explain the effects of stress on elderly women and to suggest nursing interventions. According to Roy, individuals respond to stressors in four behavioral modes: physiological, self concept, role performance, and interdependency. The results of this study indicate that, of the four groups studied in this sample, the married women were in poorest health and the most vulnerable to stress. PMID- 2324434 TI - Sexually transmitted diseases in the elderly--issues and recommendations. AB - The incidence of sexually transmitted disease (STD) in the elderly population is significant for both newly acquired disease and for residual complications from preceding infections. Every health-care practitioner needs to assume responsibility for the primary prevention of STDs, which focuses on avoiding infection. Primary health education is imperative in the presence of an escalation of sexually transmitted infection for which there is no known curative therapy. The sexual history is an integral component of the routine data base for all geriatric patients. Diagnosis of AIDS in the generally low risk elderly population may be unexpected. Health-care practitioners must be aware of its many forms of presentation. PMID- 2324435 TI - Promoting gerontic nursing. PMID- 2324436 TI - When it's hard to swallow. Feeding techniques for dysphagia management. AB - There are three phases of swallowing: oral, where the food is chewed; pharyngeal, where the bolus begins to move downward; and esophageal, where the bolus enters the esophagus. Signs of difficulty in swallowing may include difficulty initiating the swallow, packing food into cheeks, drooling, cough after a swallow or absent or weak cough, or fluid leaking from the nose after swallowing. Take your time when feeding patients and do not wash food down with liquids. Also, remember to position the patient properly and teach both the patient and his family effective feeding techniques. PMID- 2324437 TI - [Contraception and tubal sterility of infective origin]. AB - A series of 89 caucasian women, who had been operated on for non-infectious tubal infertility were studied to find out what contraceptive methods they had used before they became infertile (oral contraception, intra-uterine contraceptive device and other methods). A matched series of 178 fertile women were used as a control group. The numbers who had chlamydia were studied as a function of the method of contraception in the group of infertile women. This work shows that women with tubal infertility due originally to infection had less often used oral contraception than the matched group of fertile women had. One can conclude that oral contraception acts as a prevention against this cause of infertility. The role played by intra-uterine contraceptive devices is difficult to establish. All the same, there is a significant relationship between the use of intra-uterine devices and tubal infertility of infectious origin, whether we look at multiparae or women between 25 and 34 years of age. This study also shows that chlamydia is not associated with the use of combined preparation oral contraceptives, nor with the use of the intra-uterine device in women who have tubal factor infertility. This study all the same shows that it does seem to be important to advise oral contraception in preference to the intra-uterine device in women who are still wanting to have a pregnancy, even if they are multiparae or multigravidae. PMID- 2324438 TI - [Daily and seasonal variations in olfactory sensitivity of mothers after parturition and their capacity to discriminate the body odor of their newborn. Preliminary findings]. AB - The present study describes daily and seasonal variations in the discrimination capacities of mothers in relation to their newborn's odour and olfactory detection thresholds of a non specific molecule (thiophene) by mothers. The tests are carried out during the 2nd, 4th and 6th days after the parturition. The results show that the abilities of the mothers to discriminate the odours of their newborn increase gradually from the morning to evening, with the exception of the second part of the 4th day when the mother's performances decrease between 05:30 P.M. and 08:00 P.M. This daily variation is not observed in olfactory thresholds of mothers in relation to thiophene as they decrease between 08:00 A.M. and 01:30 P.M. and increase between 01:30 P.M. and 08:00 P.M. for the three days of test. Nevertheless, seasons, seem to have the same effect about the two types of mothers' performances. The results suggest that the variations in the abilities of the mothers to discriminate the corporal odour of their newborn and the variations of their olfactory thresholds for a non specific odour are based on different biological and psychobiological mechanisms. PMID- 2324439 TI - [Preliminary study on the transport of AZT (Retrovir-zidovudine) through the placenta]. AB - The authors selected six patients who were HIV positive and who had requested termination of pregnancy to study the passage of zidovudine through the placenta. After the patients had been warned about the procedure and given consent, 1 gram of zidovudine (Azitothymine) was given in five doses of 200 mg each orally. Ethical Committee consent had been obtained. At a mean age of 17.5 weeks of amenorrhoea, samples were taken from the mothers' blood, from the amniotic fluid and from the fetal blood between one and two hours and forty five minutes after the last dose of AZT had been taken. Pregnancy was terminated immediately after the amniotic fluid had been obtained. The levels of zidovudine and its metabolite glucuronide (G-AZT) were carried out using High Performance Liquid Chromatography (HPLC). The concentrations of the drug in the liquor and in the fetal blood were higher or equalled those found in the maternal blood. This makes it likely that the half life elimination was longer and the metabolism of the product slower when it had been metabolised to glucuronide. This study does not concern the teratogenic effect or the toxicity for the fetus. The drug remains contra indicated in pregnancy. There is no proposal at present to use it to lessen transmission of the virus from the mother to the fetus. PMID- 2324440 TI - [Flagellar anomalies in routine spermatozoa cytograms]. AB - In routine semen morphological analysis, flagellar abnormalities are often neglected. Four flagellar anomalies (absent, short, coiled and duplicated) are included in the French usual classification proposed by G. David et al. The present paper describes two new flagellar anomalies (thick and irregular) which are present in about 5% of spermatozoa in subfertile patients. These anomalies should be included in the morphological classification: first, chances of pregnancy are only correlated with precise morphological analysis. Furthermore, some infertile patients have severe asthenospermia due to flagellar anomalies which can be easily detected in routine semen analysis using this flagellar anomaly classification. PMID- 2324441 TI - [Inflammatory carcinoma of the uterine cervix. Review of 9 cases]. AB - Nine cases of inflammatory invasive carcinoma of the uterine cervix are reviewed. All appeared in women under less than fifty years old, quickly after normal PAP smears. They occupied the endocervix, which mean diameter was 5 cm and outcome was very poor with only one survivor: four patients were free of disease in the pelvis and relapsed outside, the others underwent a local regional failure in less than 2 years. Association of radiotherapy and surgery is mandatory for stage IB and IIA FIGO; radiotherapy modalities--brachytherapy, external irradiation followed by brachytherapy--must be chosen according to tumor volume, size of the cervix, anatomy of vagina. For other stages radiotherapy alone is recommended using hyperfractionated treatment; in the future such observation would be documented by cytofluorometry analysis and/or molecular biology approach. PMID- 2324442 TI - [Fatal toxic hepatitis in pregnancy. A discussion of the role of methyldopa]. AB - The authors report a case of toxic hepatitis in a woman of 22 years of age in the third trimester of her first pregnancy treated by methyldopa for hypertension of pregnancy which was diagnosed at 33 weeks of amenorrhoea. The prodromal symptoms were mild and consisted of nausea, vomiting and rise in temperature and this phase was associated with febrile jaundice without pruritus and it was only associated with coagulation disorders in the third stage of labour. This was a case of mixed cytolytic hepatitis (ASAT x 3N) and cholestasis (x 1.5N). The outcome was fatal. The patient died three days after delivery following haematemesis and renal failure as well as hepatic encephalopathy. The main diagnostic feature was acute hepatic stasis in spite of the absence of pruritus and the presence of a raised temperature after hematolytic, viral and obstructive causes had been eliminated. Histology confirmed that there was toxic hepatitis. This aetiology was suggested by the timing of the symptoms after MD (methyldopa) had been taken. Elkington described methyldopa hepato-toxicity in 1969. Fatal cases in the literature were in patients who were over 40 years of age. Methyldopa is used in pregnant women because of its safety as far as the fetus is concerned. Mechanism by which it causes toxic hepatitis is a combination of abnormal metabolism (the cytochrome P450 chain produces an antigen) and an immune reaction in response to this antigen and these explain why such severe and potentially fatal forms of the condition exist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324443 TI - [A prospective and comparative study of the outcome of children born via in-vitro fertilization and of their mothers]. AB - A prospective comparative study was carried out on the development of 40 infants born by in-vitro fertilisation (IVF) and of their relationships with their mothers. This group was compared with two control groups: Children born to infertile women after ovulation had been induced but where assisted reproduction was not used. A group of infants born after normal conception without medical intervention at all. The preliminary results at 9 months showed that there were no major developmental problems in IVF infants as compared with the controls. All the same, there are more troubles as far as sleep is concerned with IVF children and with the group of infertile mothers and these symptoms seem to be linked to difficulty in the mother-infant relationship. These troubles are minor ones and appear to be only temporary as far as can be told after 18 months. PMID- 2324444 TI - [Metabolic risks in surgical hysteroscopy]. AB - Operative hysteroscopy is often carried out using glycine as an irrigant. This solution has interesting properties but also metabolic effects that are very well known by urologists. This study is concerned with the biological changes that have occurred after one hundred surgical hysteroscopies of which twenty nine were carried out using glycine. In hysteroscopy the significant variations are concerned with blood levels of protein, the haematocrit, changes in sodium levels and glycaemia. 44.9% of patients had changes greater than 5% as compared with the pre-operative levels. These changes concerned the haematocrit readings and in 57.1% the changes in protein in the blood and in sodium in 12%. The haematocrit changes, the protein changes and to a lesser degree the sodium changes could be correlated with one another but not with changes in glycine levels in the blood. Whatever the pathology inside the uterus, glycine went through in equal quantities. It was particularly significant when there was perforation of the uterus. It is linked to the glycine balance and to the length of time the operation had taken. When a mean quantity of fluid of 2.6 litres was used to irrigate, levels after the operation as compared with before the operation had multiplied 4.5 times. This corresponds to the dosage of glycine used. In five patients out of twenty nine post-operative quantities were 10 times those before operation. The consequences of these changes in glycine levels are variable and seem to be more significant in women who have never been pregnant or who are very heavy. Using vasoconstrictor agents does not alter these metabolic changes. PMID- 2324445 TI - Care with care. PMID- 2324446 TI - Metacarpal-phalangeal joint arthroplasty of the rheumatoid thumb. AB - Fifty patients with rheumatoid arthritis had 59 Swanson implants of the metacarpal-phalangeal joint of the thumb. Eleven patients (15 implants) have since died and only 1 patient (1 implant) has been lost to follow-up leaving 43 implants available for study. The most common preoperative deformity was a boutonniere deformity with a flexible interphalangeal joint. All thumbs had less pain after operation. The average range of active motion is 25 degrees, with a flexion arc from 15 to 40 degrees. There is an average key pinch strength of 4 pounds (range, 0.5 to 10). Improvement in activities of daily living were noted in 40 hands. One thumb required reoperation for instability; the implant was removed and a metacarpal-phalangeal arthrodesis was done. Radiographic progression of disease was noted in only one thumb at the interphalangeal joint and in two other thumbs at the carpometacarpal joint. None of these have required further operations. The maintenance of motion appears to help in activities of daily living as stability and pinch strength are often adequate. PMID- 2324447 TI - Trispherical total wrist arthroplasty in rheumatoid arthritis. AB - Thirty-four patients, with 35 trispherical total wrist arthroplasties for treatment of rheumatoid arthritis, were evaluated at an average follow-up of 9 years (range, 5 to 11 years). The average preoperative score was 25 points inasmuch as all patients had severe pain and loss of function. The average postoperative score improved to 87 points since 30 wrists were free of pain. Twenty-eight wrists rated as a good-to-excellent result. The average arc of flexion and extension improved from 35 to 50 degrees. There were no deep infections or dislocations. Two wrists required revision, one for loosening and one for persistent pain, both requiring removal of the implant and arthrodesis. Postoperative tendon attrition occurred in six wrists, all of which had preoperative tendon ruptures necessitating tendon transfer. Radiographs showed radiolucencies in seven wrists, including seven around the metacarpal stem and one around the radial stem. The optimum results were achieved in those patients with intact extensor tendons before operation. PMID- 2324448 TI - A critical analysis of Swanson ulnar head replacement arthroplasty: rheumatoid versus nonrheumatoid. AB - Clinical and radiographic assessment of the results of 40 Swanson silicone ulnar head prosthesis implants in three different patient groups is presented. Twenty eight were done for treatment of rheumatoid arthritis, eight for ulnoradial impingement after the Darrach procedure, and four for ulnocarpal impingement resulting from malunited Colles' fractures. Patients were reviewed 12 to 48 months after operation (mean, 29 months). Seventy-eight percent of patients reported relief of pain and improved function. Radiologic examination showed that all patients exhibited resorption of the distal ulna (mean 4.4 mm) and that resorption was worst in the group with rheumatoid arthritis. Bone resorption about the implant predisposed the cap to both side-to-side tilt and pistoning of the prosthesis on supination and pronation. There was a 10% revision rate because of silicone synovitis. Although clinical results remain satisfactory for patients with rheumatoid arthritis and ulnocarpal impingement, the radiologic results suggest that Swanson ulnar head replacement should be restricted to elderly patients with rheumatoid arthritis. PMID- 2324449 TI - Degenerative arthritis at the triscaphe joint. AB - The clinical presentation of triscaphe arthritis and the results of arthrodesis are presented. Twenty-one patients had triscaphe arthrodesis for treatment of arthritis of the triscaphe joint between 1972 and 1986. Seven also had rotary subluxation of the scaphoid and one had Kienbock's disease. Twenty patients were available for examination at an average of 5 years after operation. All had relief of pain and the average flexion-extension arc was 101 degrees. One patient had a nonunion successfully treated by refusion, and in two patients a dystrophy developed, which was relieved by a stress loading program. No progression of arthritis was seen elsewhere in the wrist. PMID- 2324450 TI - Segmental motion of the proximal carpal row: their global effect on the wrist motion. AB - The contribution of the scapho-lunate and luno-triquetral joints to global wrist motion was studied in 11 fresh-frozen cadaver specimens. The carpus were labeled with metallic markers and the joints were selectively transfixed with wires. The wrist was allowed to follow its natural radial and ulnar deviation during flexion and extension, extension and flexion during radial and ulnar deviation, respectively. The data was collected by means of radiography, goniometric measurement, and computer analysis. The proximal carpal row (the intercalated segment) although anatomically represented as a row, presented through its two intersegmental joints, a definite segmental behavior. Each intersegmental joint of the proximal carpal row influenced global wrist motion in all directions but to a different degree for each plane of motion. The segmental joints within the intercalated segment collectively govern 40% of the wrist flexion, 33% of extension, and 10% of ulnar deviation. The scaphoid through its scapho-lunate link exerts a governing effect on total intersegmental proximal carpal row contribution to the global wrist motion. PMID- 2324451 TI - Functional range of motion of the joints of the hand. AB - Active ranges of motion of the joints of the hand are well documented, but there is little data reporting the functional ranges of motion required to perform activities of daily living. Electrogoniometric and standard methods were used to measure both active and functional ranges of motion of the metacarpalphalangeal and interphalangeal joints during 11 activities of daily living. In the fingers, only a small percentage of the active range of motion of the joints was required for functional tasks. Functional flexion postures averaged 61 degrees at the metacarpalphalangeal joint, 60 degrees at the proximal interphalangeal joint, and 39 degrees at the distal interphalangeal joint. In the thumb, functional flexion postures averaged 21 degrees at the metacarpalphalangeal joint and 18 degrees at the interphalangeal joint using only 32% of the available flexion. Active thumb metacarpalphalangeal joint motion was found to be bimodal in the study group. PMID- 2324452 TI - Architecture of selected wrist flexor and extensor muscles. AB - The architectural features of 25 wrist flexor and extensor muscles were studied. Muscles included the flexor carpi ulnaris, the flexor carpi radialis, the extensor carpi ulnaris, the extensor capri radialis brevis, and the extensor carpi radialis longus. Muscle length, mass, fiber pennation angle, fiber length, and sarcomere length (by use of laser diffraction techniques) were determined. In addition, physiological cross-sectional area and fiber length/muscle length ratio were calculated. The muscles were found to be highly specialized, with architectural features of same muscles very similar. The fiber length/muscle length ratio, muscle length, and pennation angle represented the major differences between muscles. Thus using these parameters in discriminant analysis permitted correct identification of each of the 25 muscles. In terms of size and intrinsic design, these individual muscles were highly specialized for their function. PMID- 2324453 TI - Early controlled active mobilization with dynamic splintage for treatment of extensor tendon injuries. AB - Early controlled active mobilization with a dynamic splint for treatment of repaired extensor tendon injuries was studied prospectively. Postoperative dynamic splintage started on the third postoperative day and involved elastic band extension and active flexion of the digits. Mobilization of the digits within the splint was done immediately under supervision. Range of motion was stepped up progressively and splintage was stopped after 5 to 6 weeks. Thirty eight patients with 48 digits were reviewed. The average follow-up was 6.7 months (range, 4 to 10 months). Injuries involving the fingers showed an average final total active motion of 229 degrees (range, 95 to 270 degrees), whereas injuries involving the thumb was 118 degrees (range, 78 to 150 degrees). Lesions distal to the knuckles (zones II, III, IV) showed the worst results with an average total active motion of only 188 degrees (range, 95 to 270 degrees). The duration out of work was 8.5 weeks (range, 4 to 25 weeks). There was no infection or acute tendon rupture. One patient required reconstruction of a persistent button-hole deformity; two required tenolysis and capsulotomy. Of the six unsatisfactory results with poor total active motion, four had injuries distal to the metacarpophalangeal joint, three of which were crushing injuries. PMID- 2324454 TI - Evaluation of results in flexor tendon repair: a critical analysis of five methods in ninety-five digits. AB - The development of an internationally accepted system of assessment of results after flexor tendon repair is important. In a prospective study of ninety-five digits, gross discrepancies were demonstrated between five popular methods of assessment: Buck-Gramcko, linear measurement, Grossman, American Society for Surgery of the Hand, and Strickland. The relative merits of each systems were studied and modifications for the Buck-Gramcko system are suggested. PMID- 2324455 TI - Triggering of the thumb with de Quervain's stenosing tendovaginitis. AB - Triggering with de Quervain's stenosing tenosynovitis has rarely been mentioned since de Quervain's original description. Either or both the abductor pollicis longus and extensor pollicis brevis tendons may be responsible. Without detailed examination testing specifically for triggering, the entity may be overlooked. We have encountered nine patients with triggering in the first dorsal compartment. The five with surgical release had complete resolution of symptoms; the four treated nonoperatively have improved but still have symptoms. Triggering may represent a more severe form of de Quervain's tendovaginitis. PMID- 2324456 TI - Ulnar-sided perilunate instability: an anatomic and biomechanic study. AB - A staging system for ulnar-sided perilunate instability is presented based on a series of cadaver dissections and load studies. Stage I: partial or complete disruption of the lunotriquetral interosseous ligament, without clinical and/or radiographic evidence of dynamic or static volar intercalated segment instability deformity; stage II: complete disruption of the lunotriquetral interosseous ligament and disruption of the palmar lunotriquetral ligament, with clinical and/or radiographic evidence of dynamic volar intercalated segment instability deformity; and stage III: complete disruption of the lunotriquetral interosseous and the palmar lunotriquetral ligaments, attenuation or disruption of the dorsal radiocarpal ligament, with clinical and/or radiographic evidence of static volar intercalated segment instability deformity. PMID- 2324457 TI - Microvascular anatomy of the radioscapholunate ligament of the wrist. AB - The microvascular circulation and basic structural features of the radioscapholunate ligament of the wrist were studied in six fresh cadaver specimens by injection and clearing techniques. A rich vascular supply was found to originate from vessels that perforate the palmar capsule and enter the synovium that surrounds the ligament. By way of branches from the synovium, the radioscapholunate ligament and most of the scapholunate interosseous ligament receive an abundant blood supply. No contributions are derived from the bony attachments. Observation under light microscopy revealed a delicate, well vascularized ligament consisting of regular collagen bundles. No elastic fibers were observed. This study indicates that the radioscapholunate ligament has a vascular supply that may be sufficient for healing by known methods. PMID- 2324458 TI - Nonunion of a fractured scaphoid tubercle. AB - A case of nonunion of an avulsed scaphoid tubercle fragment is reported. The fragment became surrounded with a rim of calcification and ossification. After 3 1/2 years follow-up the fragment had migrated to the carpal tunnel simulating the appearance of an accessory ossicle. PMID- 2324459 TI - An unusual combination of simultaneous fracture of the tuberosity of the trapezium and the hook of the hamate. AB - A case of simultaneous fracture of the tuberosity of the trapezium associated with fracture of the hook of the hamate is described. The mechanism of injury is thought to be traction force through the transverse carpal ligament caused by flattening of the transverse carpal arch. PMID- 2324460 TI - Limited open surgical approach for external fixation of distal radius fractures. AB - In an effort to reduce treatment-related complications, a surgical procedure has been developed for the insertion and application of an external fixation device in the management of unstable fractures of the distal radius. Clinical experience with this device has demonstrated its effectiveness in reducing complications associated with pin insertion. The surgical technique is presented together with a case example. Results of laboratory tests corroborate our clinical experience and demonstrate the effectiveness of this technique in minimizing complications. Clinical results in 66 cases document the efficacy and safety of this technique. PMID- 2324461 TI - Forearm fracture plates: to remove or not to remove. AB - Eighty dynamic compression plates used to fix fractures of the radius and/or ulna were removed from 51 of 98 adult patients. Thirty-seven patients had plates removed electively. Fourteen patients had plates removed for clinical reasons. The average time from insertion to removal was 13.6 months, with a range from 4.4 to 36 months. Only one refracture occurred through the unhealed both bone forearm fracture site in a patient whose plate was taken out 6 months after surgery. One refracture also occurred through the proximal screw hole of a still implanted ulna plate that had been inserted 3 years earlier. Leaving a plate in for the remaining life of a young patient cannot be considered a benign decision considering the persisting chance for refracture and the potential complications from prolonged exposure to metal corrosion complexes and metal ions. PMID- 2324462 TI - Irreducible palmar dislocation of the proximal interphalangeal joint of the finger. AB - Three patients with palmar dislocations of the proximal interphalangeal joints are described. The causes of irreducibility were the interposition of one lateral band about the condyle of the middle phalangeal head in two patients and the interposition of the central slip in one patient. PMID- 2324463 TI - Microsurgical revascularization of ischemic rat femoral heads. AB - To demonstrate whether revascularization could be surgically induced in avascular bone the femoral heads of female albino rats were excised and drilled through and through. The femoral heads were then placed in the opposite thigh and by use of microvascular techniques the femoral artery was divided and lengthened with a 1 cm artery or vein graft, and reanastomosed after passing one end through the drilled hole in the transplanted femoral head. Arterial blood flowed through the graft within the drilled femoral head on its way to its normal distribution down the leg. Technetium 99m MDP methylene diphosphate, tetracycline labeling, latex injection, and histologic review were used to demonstrate new vessel growth. All grafts patent at the end of the experiment were associated with tetracycline labeling, positive technetium 99m methylene diphosphate counts and latex-filled vessels in the matrix of the femoral heads. Histologically the vascularized femoral heads showed evidence of neovascularization and new bone formation. PMID- 2324464 TI - Reconstructive microsurgery of the upper extremity. PMID- 2324465 TI - Serratus anterior muscle transplantation for treatment of soft tissue defects in the hand. AB - The inferior three slips of the serratus anterior muscle have been used as a free tissue transfer in 18 patients for the reconstruction of dorsal and palmar defects in the hand. Mean follow-up was 2.8 years. There were 12/18 flaps for palmar coverage and 6/18 for dorsal coverage. All flaps survived. On the basis of this experience we conclude that this flap has three attributes making it suitable for palmar and dorsal metacarpal resurfacing: (1) low donor site morbidity, (2) the three separate slips are easily divisible for contouring, and (3) durability and adhesion provide a stable resurfacing for grasp. PMID- 2324466 TI - Clinical results of bony fixation methods in digital replantation. AB - Clinical results comparing different techniques of fixation in replanted digits have not been described in detail, and bony deformities after replantation have been documented only in limited series. We retrospectively analyzed our population of phalangeal replants over a 5-year period to assess the outcome of different fixation methods with regard to frequency of angulation, fracture instability, nonunion, and need for corrective osteotomy. Techniques evaluated included: single and crossed Kirschner wires, intraosseous wires with and without Kirschner wire support, and the tetrahedral (Cassel) wire. Initial results show similar early angulation deformities in all groups. Intraosseous wires alone were found to have the lowest nonunion and complication rate. The Cassel wire was found to have the highest number of digits with fixation problems. Overall, bony problems were seen in nearly 50% of replants in our series. PMID- 2324468 TI - Percutaneous phenol block of the musculocutaneous nerve to control elbow flexor spasticity. AB - Twenty-three extremities in 17 brain-injured adults were prospectively studied to evaluate the effectiveness of percutaneous phenol blocks of the musculocutaneous nerve in controlling spasticity of the biceps and brachialis muscles. Twenty-one (93%) of the extremities improved after the initial injection. The mean resting position decreased from 120 degrees of flexion to 69 degrees. Elbow range of motion increased an average of 53 degrees. There were no complications. Two patients did not respond to the initial injection and required repeat nerve blocks. Concomitant phenol motor point block of the brachioradialis muscle further improved elbow motion. The mean duration of the block was 5 months. Follow-up averaged 21 months. This study indicates that percutaneous phenol injection of the musculocutaneous nerve provides reliable, temporary relief of spasticity in patients with potential for further neurologic improvement. PMID- 2324467 TI - Electromyographic analysis of brachioradialis to flexor pollicis longus tendon transfer in quadriplegia. AB - Electromyography was done in patients at the C6 level of quadriplegia after transfer of the brachioradialis to the flexor pollicis longus to restore lateral pinch and transfer of the posterior deltoid to the triceps to restore elbow extension. The relationship of the integrated electromyogram to pinch force during a graduated isometric contraction enabled characterization of the motor recruitment pattern. After tendon transfer, the pattern of the electromyographic response for the brachioradialis was the same as in the flexor pollicis longus in normal subjects, and the posterior deltoid after transfer to the triceps fired synergistically with the brachioradialis. These findings indicate reeducation of transferred muscles occurred after surgery and that they functioned as active primary motors. PMID- 2324469 TI - Incidence of anatomic variants in Guyon's canal. AB - This study was undertaken to determine the frequency of variations involving the anatomy of Guyon's canal. A series of 58 wrist dissections revealed a 22.4% incidence of anomalous muscles and a 1.7% incidence of anomalous nerve paths. The relationship of the deep branch of the ulnar artery to the superficial and deep branches of the ulnar nerve was found to vary. Accessory muscles passing through Guyon's canal are common, and are often found bilaterally. Aberrant branching of the ulnar nerve in this area is rare. PMID- 2324470 TI - Median innervated hypothenar muscle: anomalous branch of median nerve in the carpal tunnel. AB - A hypothenar motor branch of the median nerve in the carpal tunnel was observed and its motor function was documented by direct intraoperative nerve stimulation in two patients having carpal tunnel releases. The hypothenar branch left the median nerve at the midcarpal tunnel area. It crossed the tunnel superficial to the flexor tendons and penetrated the transverse carpal ligament ulnarly to innervate the abductor digiti quinti. Such branching of the median nerve at this level has not been reported previously. Good visualization of the carpal tunnel and careful dissection of its content even in the so called safe zone ulnar to long axis of palmaris longus tendon is recommended. PMID- 2324471 TI - A self-administered hand diagram for the diagnosis of carpal tunnel syndrome. AB - A self-administered hand diagram has been developed to assist in the evaluation of upper extremity paresthesias. A rating system was devised to classify diagrams into four categories: classic, probable, possible, or unlikely carpal tunnel syndrome. Diagram ratings of 63 patients (85 hands) evaluated in a hand clinic were compared with diagnoses established independent of diagram results by objective clinical criteria. The sensitivity of diagrams rated classic or probable was 80% and specificity was 90%. We conclude that the hand diagram is valuable in the diagnosis of carpal tunnel syndrome among patients with upper extremity paresthesias. PMID- 2324472 TI - Bilateral palmaris profundus causing bilateral carpal tunnel syndrome. AB - Only a few cases of palmaris profundus have been reported in the English-language literature. The palmaris profundus is a rare anomalous muscle of the forearm that may cause carpal tunnel syndrome. We describe the first case of bilateral palmaris profundus associated with bilateral palmaris longus causing bilateral carpal tunnel syndrome. PMID- 2324473 TI - Distal rupture of the palmaris longus tendon and fascia as a cause of acute carpal tunnel syndrome. AB - Acute carpal tunnel syndrome is rare compared with its more chronic presentation. Previous reports in the literature have documented the most common causes. Rupture of the distal palmaris longus tendon into the palmaris fascia as a cause of an acute carpal tunnel syndrome has not been reported previous to this case report. Partial rupture of the tendon and hemorrhage around its insertion produced intrinsic compression on the transverse ligament and the underlying nerve. PMID- 2324474 TI - Intraosseous compression wiring of displaced articular condylar fractures. PMID- 2324475 TI - Use of a step-cut osteotomy for immediate posttraumatic proximal interphalangeal joint fusion. PMID- 2324476 TI - Terminology and its application to computer-aided data processing in digestive endoscopy. AB - Endoscopic word database systems are not standardized. An endoscopic word reference has been developed by the World Organization for Gastrointestinal Endoscopy. The suggestion is made to develop a standard software program for gastrointestinal endoscopy based on this system or one similar. PMID- 2324478 TI - The effect of age on the relative potency of midazolam and diazepam for sedation in upper gastrointestinal endoscopy. AB - Diazepam and midazolam are considered safe and effective sedative agents for diagnostic procedures. However, there have been recent reports of deaths in older patients receiving midazolam for sedation. We examined the relative potency of diazepam compared with midazolam as a function of age in two large groups of patients receiving intravenous benzodiazepines for upper gastrointestinal endoscopy. While midazolam and diazepam are approximately equivalent before age 60, after age 60 the relative potency of midazolam compared with diazepam increases markedly. The rapid decline in dose necessary to sedate older patients with midazolam may explain deaths occurring in older patients who have received this drug. Until this problem receives definitive study, we advise that diazepam be preferred over midazolam for intravenous sedation in patients over 60. PMID- 2324477 TI - The diagnostic value of upper gastrointestinal radiography. AB - We reviewed the indications for and results of 788 consecutive upper gastrointestinal radiographs (UGIs) performed for ambulatory patients. Sixty three percent of tests were ordered for the evaluation of abdominal pain, dyspepsia, or esophageal reflux. Of these tests, only 4.8% yielded results of major clinical importance to patient management. The yield for patients greater than 50 years of age was greater than for patients less than 50, 6.9 versus 3.0% (p = 0.04). There was a significant increase in yield with increasing age (chi trend = 11.6, p less than 0.001). Among patients with an indication of esophageal reflux alone (n = 62), there were no patients younger than age 60 with a test result that would significantly affect therapy or outcome. Among patients evaluated for fecal occult blood or weight loss (n = 120), 11.7% of tests ordered showed a finding of major clinical importance. In this group, the yield was higher in those greater than or equal to 50 years of age than in those less than 50, 14.7 versus 6.7%, (p = 0.2). These results indicate that UGIs ordered to evaluate pain or symptoms of esophageal reflux in the absence of bleeding or weight loss rarely yield results that significantly influence therapy. Such patients may be best served by an initial trial of empiric therapy or some other test. The UGI has greatest value when indications for it include bleeding or weight loss. PMID- 2324479 TI - Aeromonas in adult diarrhea: an enteropathogen or an innocent bystander? AB - This is a study from a district hospital in Israel serving a population of 250,000. During 1986-1987, 1,005 stool specimens were cultured from 932 adult inpatients with acute diarrhea. Seventeen yielded Aeromonas species. Of the 12 strains phenotyped, 10 qualified as enteropathogenic. Five hundred stool specimens from asymptomatic control subjects, inhabitants of the same region, were negative for Aeromonas. The finding of Aeromonas as the apparently sole pathogen in acute adult diarrhea in a geographical area with a negligible asymptomatic carriage rate lends support to the possibility that Aeromonas is an enteropathogen in adults. PMID- 2324481 TI - Esophageal involvement by cutaneous T-cell lymphoma, mycosis fungoides type: diagnosis by endoscopic biopsy. AB - A patient with long-standing cutaneous T-cell lymphoma, mycosis fungoides type (CTCL-MF), developed dysphagia, odynophagia, and weight loss. Endoscopic biopsy of esophageal mucosa demonstrated involvement by CTCL-MF. Although extracutaneous spread of CTCL-MF is common, esophageal involvement is unusual and to our knowledge has not previously been diagnosed antemortem. PMID- 2324480 TI - Jejunal water and sodium secretion occurs in chronic idiopathic intestinal pseudo obstruction. AB - We observed jejunal water and sodium secretion in two patients with chronic idiopathic intestinal pseudo-obstruction by standard perfusion techniques. The ability of glucose to reverse this secretory state was impaired. These observations suggest that a jejunal secretory state may contribute to the diarrhea in chronic idiopathic intestinal pseudo-obstruction. PMID- 2324482 TI - Clostridium difficile-associated diarrhea after norfloxacin. AB - Although theoretically the spectrum of antimicrobial quinolone antibiotics are at low risk of producing Clostridium difficile overgrowth and diarrhea, a patient developed this clinical problem while receiving norfloxacin. We review the antimicrobial activity of the quinolone antibiotics, with respect to their predisposition for producing C. difficile-induced diarrhea. PMID- 2324483 TI - Long-standing symptomatic cryptosporidiosis in a normal man: clinical response to spiramycin. AB - A healthy immunocompetent 26-year-old man developed prolonged symptomatic cryptosporidiosis. He only achieved clinical improvement after treatment with spiramycin. Other family members suffered from chronic undiagnosed diarrhea, and resolution occurred only after a trial of spiramycin. Thus, Cryptosporidium had provoked a prolonged symptomatic infection in a normal host; spiramycin therapy was required for parasite eradication and clinical cure, and a therapeutic trial with spiramycin was beneficial for family members with chronic undiagnosed diarrhea. Many infections with Cryptosporidium have serious morbidity, and thus, spiramycin may be more generally indicated in the treatment of this infection. PMID- 2324484 TI - Cholecystocolonic fistula: malabsorptive consequences of lost bile acids. AB - A patient with the painless onset of a cholecystocolonic fistula associated with virtually complete common bile duct obstruction due to stones provided a unique opportunity to assess the consequences of prolonged bile acid depletion on the digestion and absorption of nutrients. Over 2 years, the patient insidiously developed steatorrhea, osteomalacia with an atraumatic pelvic fracture, and congestive heart failure complicated by polymorphic ventricular tachycardia (torsade de pointes) all of which could be attributed to malabsorption of fat and fat-soluble vitamins. PMID- 2324485 TI - Herbal hepatitis: subacute hepatic necrosis secondary to chaparral leaf. AB - A 33-year-old woman developed subacute hepatic necrosis after several months of ingestion of Chaparral Leaf, an herbal product. Symptoms first appeared 3 months after she began taking the tablets. The patient unwittingly carried out a clinical challenge by reducing, then increasing, the dose of pills. The public and the medical profession must be wary of all "harmless" nonprescription medications, whether purchased in pharmacies or elsewhere. PMID- 2324486 TI - Esophageal carcinoma in Indian Jews of southern Israel. An epidemiologic study. AB - The incidence of esophageal cancer varies in different populations and localities. The varied composition of the immigrant population of southern Israel afforded us an opportunity to investigate the frequency of the disease. The results of a retrospective study (1961-1985) revealed a high mean age-adjusted incidence rate (per 10(5)) in immigrant Indian men (6.5 +/- 2.17) and Indian women (17.2 +/- 5.12). Rates in all non-Indian immigrants were significantly lower: men 2.7 +/- 1.19, women 2.1 +/- 0.24. The relative risk of developing the disease was significantly higher in Indians. The age at diagnosis was lower in Indian women (54.6 +/- 10.4 years) than Indian men and other immigrants (p less than 0.05). The clinical features were similar in all cases. The risk factors in Indian men were not apparent; in women, the indiscrete use of spices might have raised the rate of esophageal cancer. The disease is more frequent in Indian populations in several parts of the world, and vigilance is required on the part of physicians. PMID- 2324487 TI - Gallstone ileus following endoscopic sphincterotomy. PMID- 2324488 TI - The rumination syndrome in an adult patient. PMID- 2324489 TI - Osler-Weber-Rendu disease associated with hepatic involvement and high output heart failure. PMID- 2324490 TI - Portal, mesenteric, and splenic venous thrombosis after endoscopic injection sclerotherapy. PMID- 2324491 TI - Superior vena caval syndrome 5 years after peritoneovenous shunt for ascites. PMID- 2324492 TI - "The liver and gallbladder flush". PMID- 2324493 TI - Upper GI bleeding from below the descending duodenum. PMID- 2324495 TI - Partial characterization of a C5a-inhibitor in peritoneal fluid. AB - We have recently described a 40-kDa protein in peritoneal fluid that neutralized the chemotactic activity of the C fraction C5a. It was deficient in peritoneal fluids of patients suffering from familial Mediterranean fever. Further characterization of the inhibitor with the use of 125I-rC5a binding to dibutyryl cAMP-induced U937 cells revealed dependence on the peritoneal fluid concentration, on the time of incubation and on temperature and pH. Fractionation of 125I-C5a on Sephadex G-50 column, before and after incubation with peritoneal fluid, revealed similar fractionation patterns despite loss of biologic activity of the treated C5a (but not its binding to polyclonal anti-C5a antibody). Analysis of rC5a by SDS-PAGE before and after treatment with partially purified C5a inhibitor, revealed slight modification of the inhibitor-treated C5a. Using various protease inhibitors (i.e., PMSF) suggested that the C5a inhibitor is a serine protease. It neutralized C5a by means of limited proteolysis which did not change C5a immunologic properties and changed only slightly its m.w. but abolished its receptor binding and chemotactic functions. It is suggested that the C5a inhibitor plays a role in the regulation of inflammation in serosal tissues and that its deficiency in familial Mediterranean fever may explain the attacks of sterile inflammation characteristic of this disease. PMID- 2324494 TI - Aqueous humor contains transforming growth factor-beta and a small (less than 3500 daltons) inhibitor of thymocyte proliferation. AB - The anterior chamber of the eye is an immunologically privileged site in which allografts survive longer than at other body sites. In this regard, it is relevant that aqueous humor (AH) inhibits lymphocyte proliferation. In order to analyze AH for specific substances that inhibit thymocyte proliferation, samples of human AH, murine AH, and rhesus monkey AH were added to cultures of thymocytes stimulated by IL-1 or IL-2 in the presence of PHA. All samples of AH tested had potent inhibitory activity on thymocyte proliferation in this system. Inhibitory activity was lost by heating AH to 80 degrees C for 1 h. Dialysis of murine AH indicated that species smaller than 3500 Da were capable of mediating this activity; we have termed the factor(s) responsible for this "small inhibitory factor(s) of AH." Retentate, containing species larger than 3500 Da, retained inhibitory activity, but less than nondialyzed AH. Assays for PGE2 demonstrated that murine and human AH contained small quantities of PGE2. These quantities were insufficient to inhibit thymocyte proliferation in our assay system. Furthermore, AH from mice treatend with indomethacin had full inhibitory activity. Assays for transforming growth factor beta (TGF-beta) after acid activation demonstrated significant quantities of latent TGF-beta within human and murine AH which could be largely neutralized by antisera to TGF-beta. Active TGF-beta "activity" was also present without acid activation in samples of AH at a level approximately 20% that of latent TGF-beta. However, most of this "activity" could not be neutralized by antisera to TGF-beta. AH contains factors capable of limiting thymocyte proliferation. PMID- 2324496 TI - Regulation of the membrane attack complex of complement. Evidence that C8 gamma is not the target of homologous restriction factors. AB - Inability of the membrane attack complex of C (C5b-9) to efficiently lyse E from the same species has been attributed to one or more membrane-associated proteins that are collectively called homologous restriction factors. These include a 65,000 Mr protein referred to as the C8 binding protein or homologous restriction factor and a 20,000 Mr protein referred to as P-18, HRF20, CD59 Ag, or MIRL. Both are found on nucleated cells as well as E and both protect against complement mediated lysis by interfering with C8 and/or C9 function within C5b-9. The exact mechanism by which these factors restrict activity is unknown but studies with purified C8 binding protein suggest they may interact specifically with the gamma subunit of C8. To determine directly if gamma is the target of restriction factors, a derivative of human C8 lacking this subunit was evaluated for its potential to lyse homologous cells. This derivative (C8') was previously shown to be functionally equivalent to normal C8 in a heterologous sheep E system. Here, it is compared to normal C8 by using human E as target cells. Results indicate no difference between the ability of C8 and C8' to incorporate into HuEAC1-7, to mediate subsequent C9 binding and to promote hemolysis. Thus, the presence or absence of gamma has no effect on homologous restriction of C5b-9, therefore gamma cannot be the primary target of homologous restriction factors. PMID- 2324497 TI - In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins. AB - Eosinophil infiltration and degranulation around the tissue-invasive stages of several species of helminths have been observed. Release of eosinophil granule contents upon the worms is supported by localization of two of the major granule proteins, major basic protein (MBP) and eosinophil peroxidase (EPO), on and around species of trematodes, nematodes, and cestodes. In the case of filarial worms, MBP is deposited on degenerating microfilariae (mf) of Onchocerca volvulus. Here, we performed in vitro assays of the toxicity of four purified eosinophil granule proteins, namely, MBP, EPO, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), for the mf of Brugia pahangi and Brugia malayi. MBP, ECP, and EDN killed these worms in a dose-related manner although relatively high concentrations of EDN were necessary. EPO, in the presence of a H2O2-generating system and a halide, was the most potent toxin on a molar basis; here, the most potent halide was I- followed by Br- and Cl-. Surprisingly, EPO in the absence of H2O2 killed mf at concentrations comparable to those required for MBP and ECP. The toxicity of EPO + H2O2 + halide was inhibited by heparin, catalase, or 1% BSA, whereas the toxicity of EPO alone was inhibited only by heparin. Heparin also inhibited killing by both MBP and ECP. Despite the homology of ECP with certain RNases, placental RNasin, an RNase inhibitor, was unable to inhibit ECP-mediated toxicity. These results indicate that all of the eosinophil granule proteins are toxic to mf and they support the hypothesis that eosinophil degranulation causes death of mf in vivo. PMID- 2324498 TI - An immunogenic Mr 23,000 integral membrane protein of Schistosoma mansoni worms that closely resembles a human tumor-associated antigen. AB - A Mr 23,000 Ag of the human trematode parasite, Schistosoma mansoni, has been identified by immunoscreening an adult worm cDNA library with antibody affinity purified on the Mr 23,000 to 25,000 integral membrane protein fraction of the parasite. This Ag is immunogenic in infected humans as well as in rabbits exposed to S. mansoni. The protein sequence of the Ag as deduced from cloned DNA sequences is 218 amino acids long and contains four putative transmembrane regions. Of particular significance, the Ag is strikingly similar, with respect to both amino acid sequence (36% identity) and putative domain structure to ME491, a human stage-specific melanoma-associated Ag. PMID- 2324499 TI - Cloning and expression of a chimeric antibody directed against the human transferrin receptor. AB - The cloning, construction and expression of chimeric Ig genes, encoding a mAb directed against the human transferrin receptor, is described. From a mouse hybridoma cell line, secreting an antitransferrin receptor antibody, mRNA was prepared and converted into cDNA using Ig-specific oligonucleotides. H and L chain encoding cDNA fragments were isolated and sequenced. Chimeric genes were constructed by linking the murine V region cDNA fragments to human C region exons. After sequential transfection of nonproducing mouse hybridoma cells with the expression vectors containing the chimeric H and L chain genes, antibody secreting transfectomas were obtained. ELISA and immunoblot analysis clearly demonstrate the secretion of human kappa- and gamma-1 chain. Flow microfluorimetry analysis of the chimeric antibody shows that the Ag-binding capacity has been retained. The chimeric antibody most likely will be less immunogenic then the original mouse antibody when used in human cancer therapy. PMID- 2324500 TI - Quantitation of C4 nephritic factor by an enzyme-linked immunosorbent assay. AB - We have developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of C4 nephritic factor (C4NeF). Incubation of the C4NeF-positive serum from patient M.I. with normal human serum (NHS) in the presence of human aggregated IgG (AHG) resulted in the formation of stable C4-C2 complex. No complex was formed in EDTA or under the condition free of AHG. The reaction mixture was filtered through an ACA 22 column, from which the C4-C2 complex was eluted at the first protein peak. When IgG purified from M.I. serum was incubated with NHS and AHG, C4-C2 complex also increased in proportion to dose of the purified M.I. IgG. These results show that C4NeF in M.I. serum stabilizes C4b2a convertase of the classical complement pathway, and is quantified by the ELISA. C4NeF activity was measured, using the ELISA method, in patients with various glomerular diseases, and found elevated in three of 24 patients with membranoproliferative glomerulonephritis (MPGN) type I and slightly but distinctly positive in seven of 24. No C4NeF was detected in two C3 nephritic factor-positive patients with MPGN type II and six with active systemic lupus erythematosus. The new method was more simple and quantitative than C4b2a stabilization assay for C4NeF. PMID- 2324501 TI - Immunochemical properties of malondialdehyde-protein adducts. AB - Malondialdehyde (MDA), a product of lipid peroxidation, can bind to and modify proteins by adduct formation. To determine whether MDA adducts were immunogenic, MDA was added to rabbit serum albumin (RSA) in order to characterize MDA-proteins and to immunize rabbits. Bound MDA was proportional to the concentration of MDA added in the range of 2.5-20 mM as measured by thiobarbituric acid reactivity. MDA adducts of RSA migrated further toward the anode than native serum protein in zone and immunoelectrophoresis indicating increased negative charge. Rabbits immunized with MDA-RSA produced high titers of IgG antibodies to MDA-RSA as measured by enzyme-linked immunosorbent assay (ELISA). Hapten specificity of the antibody was demonstrated by antisera reactivity with MDA-RSA but not with unaltered RSA. Our findings support the possibility that MDA may serve as a hapten to form neoantigens which may represent a pathway by which lipid peroxidation could produce tissue damage via an immunologic mechanism. PMID- 2324502 TI - Checkerboard immunoblotting (CBIB): an efficient, rapid, and sensitive method of assaying multiple antigen/antibody cross-reactivities. AB - A simple technique, checkerboard immunoblotting (CBIB), is described, which facilitates the examination of multiple antigen/antibody interactions, conveniently and reproducibly, using minimal amounts of reactants. Antigens, immobilized on a solid-phase membrane in parallel lanes, are allowed to react with primary antibodies, applied in lanes perpendicular to the antigens, and the reactions are developed with appropriately labeled secondary antibody and substrate. Positive reactions, at the intersections of antigen/antibody lanes, are small squares, giving a checkerboard appearance to the blot. The results are easily read visually and presented in the form of a permanent record. CBIB has wide range of applications, including the screening of hybridomas for monoclonal antibody production. With the cholera toxin (CT)-related antigens used, homologous reactions were markedly stronger then heterologous reactions. PMID- 2324503 TI - Analysis of proliferation and terminal differentiation of HL-60 human promyelocytic leukemia cells by a rapid colorimetric assay. PMID- 2324504 TI - A new sandwich enzyme-linked immunosorbent assay (ELISA) for transforming growth factor alpha (TGF alpha) based upon conformational modification by antibody binding. AB - A sandwich-type enzyme-linked immunosorbent assay (ELISA) for human TGF alpha was established utilizing monoclonal and polyclonal anti-synthetic human TGF alpha antibodies with defined epitopes. A polyclonal antibody which was raised in a rabbit and affinity purified by C terminal peptide (hTGF alpha (34-50)) recognized both intact and denatured human TGF alpha. Murine monoclonal antibodies isolated bound only to the denatured form of TGF alpha at the second loop (hTGF alpha (16-33)). However, the rabbit antibody was found to induce a conformation change of intact TGF alpha and the resultant immunocomplex was recognized by monoclonal antibodies. By virtue of this property, the ELISA could detect both native and denatured TGF alpha with the same efficiency with a detection limit of 0.1 ng/ml. Human EGF did not interfere with the ELISA. Production of TGF alpha in several transformed human cell lines was quantitatively examined. Some cell lines were found to secrete TGF alpha, but the production rate was very low, except one melanoma, suggesting that TGF alpha may function only locally in a very limited area in vivo. PMID- 2324505 TI - Practical method for production of monoclonal antibody to human IgG allotype G1M F and its applications in ELISAs and dot immunobinding. AB - An anti-G1M F monoclonal antibody was produced by immunization of mice with a single dose of F(ab')2 fragments of normal IgG1-enriched IgG and subsequent fusion of their lymph node cells with P3U1 myeloma cells. Antibody specificity was tested by an ELISA in microtiter plates coated with allotype positive or negative IgG. The usefulness of the antibody as a G1M F typing reagent in inhibition and direct immobilization-type ELISAs and dot immunobinding was demonstrated by re-typing of 100 GM-allotyping control sera. The advantages and disadvantages of these assay methods are discussed. PMID- 2324506 TI - Secretory IgA, IgG, and IgM immunoglobulins isolated simultaneously from colostral whey by selective thiophilic adsorption. AB - In order to evaluate the collective contribution of immunoglobulins to gastrointestinal and immune system development in newborn infants, it would be advantageous to develop a simple and rapid procedure for the selective and quantitative removal of all immunoglobulin classes from colostrum and milk. Toward this end, the major immunoglobulin classes typically present in colostrum (IgM, sIgA, and IgG) have been isolated simultaneously by selective removal from a porcine colostral whey model system using a single-step, preparative scale procedure termed thiophilic adsorption. At neutral pH, the salt-promoted thiophilic affinity of immunoglobulins for the synthetic sulfone-thioether ligands exploits a common (as yet unknown) structural feature of immunoglobulins. The adsorption and recovery procedures operate efficiently under mild buffer conditions permitting the subsequent comparative biochemical analyses of individual immunoglobulin classes for structural and functional heterogeneity. Thus, 1 liter columns of thiophilic adsorbent (T-gel) were employed to obtain pure, structurally intact immunoglobulins from 1 liter batches of porcine colostral whey. The identity and purity of the isolated immunoglobulins were determined under both structure-stabilizing ('native') conditions and denaturing conditions using high-performance size-exclusion chromatography, sucrose density gradient centrifugation, immunodiffusion techniques, SDS-polyacrylamide gradient gel electrophoresis with immunoblotting identification procedures, and two dimensional electrophoresis. This is the first procedure known to us that allows for the simultaneous one-step isolation (under homologous conditions) of various immunoglobulins with preserved quaternary structure and apparent biological activity. PMID- 2324507 TI - Purification of human immunoglobulins by sequential precipitation with caprylic acid and ammonium sulphate. AB - We have tested the usefulness of sequential precipitation with caprylic acid and ammonium sulfate to purify human monoclonal and polyclonal immunoglobulins from sera of 11 patients with monoclonal gammapathy (4 IgG kappa, 2 IgG lambda, 2 IgM kappa, 1 IgA kappa, 2 IgA lambda), four patients with autoimmune diseases and four healthy donors. In terms of purity and activity of Ig as well as execution time and cost, this two-step non-chromatographic procedure is highly efficient for the purification of IgG, IgA and IgM, thus offering several advantages over other methods of purification. Therefore, this procedure may have useful application in the preparation of human Ig for structural studies and therapeutic purposes. PMID- 2324508 TI - A novel affinity purification method to isolate peptide specific antibodies. AB - Site-specific, high affinity polyclonal antisera are effectively and successfully produced by immunizing rabbits with synthetic peptides. The use of these antisera in subsequent immune analysis is often limited because of non-specific binding. We describe a new and simple method to effectively affinity-purify anti-peptide antibodies. To test our system, rabbits were immunized with model peptides representing sequences of the putative rabbit growth hormone receptor and several HLA-DQ beta-chain molecules. Polystyrene plastic beads were coated with peptides. Immune serum was incubated with the beads and after a wash step the bound antibodies were eluted in 1 M acetic acid. The eluted material was composed predominantly of intact immunoglobulin as evidenced by the presence of heavy and light chain bands in SDS-PAGE. The eluted antibodies were peptide specific in ELISA and bound only to intact, antigenic protein in immunoblot analyses. The sequence-specific nature of the eluted antibodies was confirmed since binding to the antigenic proteins could be displaced by the immunizing but not by unrelated peptides. PMID- 2324509 TI - Preparative procedures of cooling and re-warming increase leukocyte integrin expression and function on neutrophils. AB - The majority of studies involving neutrophil integrin expression and function are performed at physiological temperatures subsequent to routine preparative procedures at 4 degrees C. We have shown that surface expression of the leukocyte integrin molecules on neutrophils is increased by cooling and subsequently re warming of neutrophils to 37 degrees C when compared with cells held at room temperature or 37 degrees C. This increase in expression is secondary to prior cooling of the neutrophils. There is an associated increase in function of these newly expressed adhesion molecules, making the neutrophils more adherent to endothelium. Preparation of cells at 4 degrees C and subsequently warmed to 37 degrees C is stimulatory for neutrophils, probably causing translocation of intracellular stores of the leukocyte integrins to the cell surface in a manner analogous to the stimulant FMLP. Our results indicate that the cooling of neutrophils during isolation is an inappropriate method of neutrophil preparation. PMID- 2324510 TI - Increased immunogenicity of a non-amphipathic protein (BSA) after inclusion into iscoms. AB - Bovine serum albumin (BSA) was used as a non-amphipathic model protein to be included into iscoms. Pretreatment at an acidic pH (2.5) was used to reveal hydrophobic regions, after which BSA could be integrated. In immunization experiments in mice the BSA iscoms induced long lasting and considerably higher serum antibody responses than non-treated monomeric BSA or BSA aggregated by acidic treatment. PMID- 2324511 TI - A specific, sensitive radioimmunoassay for platelet-activating factor (PAF). AB - A specific radioimmunoassay (RIA) has been developed for platelet-activating factor (PAF) and shown to be sensitive over the range 10-1000 pg (0.02-2 pmol). The anti-PAF antibodies showed specificity for the acetyl group at the C2 position of the PAF molecule and exhibited no significant cross-reactivity with lyso-PAF or the naturally occurring lipids including lecithin and lysolecithin. The sensitivity of the RIA was at least as good as the platelet-based assays for PAF but the RIA was simpler to perform, had a higher capacity and did not have the drawback of the inherent variability associated with the bioassays. PMID- 2324512 TI - An avidin-biotin ELISA for the measurement of mitochondrial aspartate aminotransferase in human serum. AB - We describe a new double-antibody ELISA system using avidin-biotin amplication for the mass measurement of mitochondrial aspartate aminotransferase (m-AST) in human serum. The assay is very sensitive and as little as 0.5 ng/ml of m-AST may be detected. The method is linear up to 100 micrograms/l. The within-day and day to-day coefficients of variation were found to be 8.9% and 11.5% respectively for a low m-AST concentration (2.7 micrograms/l), and 5.9% and 8.0% respectively for a high level of m-AST (30 micrograms/l). The assay requires 100 microliters of serum and can be completed within 5 h. The ELISA procedure and a classical immunoprecipitation technique measuring the catalytic activity of the isoenzyme were applied simultaneously to the sera of 189 subjects. The protein levels determined by ELISA correlated poorly (r = 0.66) with the catalytic activity of m AST. PMID- 2324513 TI - A one step cell sorting procedure for the enrichment of murine bone marrow CFU-S which is independent of their proliferative activity. AB - Murine bone marrow day 9 splenic colony-forming units (CFU-S) have been concentrated using a one step cell sorting technique. CFU-S were discriminated on the basis of their rather high forward light scatter intensity, their high affinity for the lectin WGA and the absence of a cell surface marker expressed by the majority of hematopoietic cells and recognized by the RA3-5B3 MoAb. This procedure permitted a 40-fold enrichment of quiescent or cycling CFU-S (obtained from normal and Ara-C-treated mice respectively) and did not alter their differentiation pathways towards the various myeloid lineages. PMID- 2324514 TI - Sensitivity of B16 melanoma sublines to lymphokine-activated killer cells as determined by 51Cr-release and clonogenic assays. AB - The aim of this study was to compare the differential sensitivities of B16 melanoma sublines to LAK cells by means of the standard 51Cr release assay and a clonogenic assay, which measures both cell survival and proliferation. LAK cells, generated after 4 days incubation with 150 international units (IU)/ml of interleukin-2 (IL-2), showed both cytolytic and anti-proliferative activities against B16 targets. Using an 18 h 51Cr release assay, murine LAK cells showed the highest cytolytic activity against B16 parental cells compared to B16-F1, B16 F10, B16-FLR and B16-BL6 sublines at effector/target (E/T) ratios ranging from 6/1 to 100/1. Purified adherent LAK (A-LAK) cells showed greater cytolytic activity against B16 parental cells and other B16 sublines compared to LAK cells, but otherwise the pattern of reactivity was similar. Using a clonogenic assay, the surviving fraction of B16 parental cells co-cultivated with LAK cells decreased to 0 at an E/T ratio of 50/1, while a 400/1 ratio was required to achieve a similar reduction of B16-F1, B16-F10, B16-FLR, and B16-BL6 sublines. No differences in subline sensitivity were seen with the 51Cr release assay, but these were observed using the clonogenic assay. An inverse linear relationship existed between % surviving fraction, as determined by the clonogenic assay, and cytolytic activity, as determined by the 51Cr release assay. Our data indicate that the clonogenic assay can detect differences in target cell sensitivity that otherwise are undetectable by the standard 51Cr release assay. The clonogenic assay may prove useful in delineating the long-term anti-adherent and anti proliferative properties of effector cells from their cytolytic activity. PMID- 2324515 TI - Recovery of infectious human immunodeficiency virus from cells treated with 1% paraformaldehyde. AB - Fixation and preservation of cells with 1% paraformaldehyde is a common practice in laboratories performing flow cytometric analysis of cells from persons infected with human immunodeficiency virus (HIV). Previous studies indicated that 1% paraformaldehyde effectively inactivates cell-free HIV. In this study, we tested the inactivation capacity of 1% paraformaldehyde on a cell line chronically infected with HIV and human peripheral blood lymphocytes acutely infected with the virus. We found a significant decrease in the infectious titer of the cells after treatment with 1% paraformaldehyde. However, we did not find total inactivation of the specimens treated for up to 18 h. PMID- 2324516 TI - The urease ELISA for H-Y antibody. A cautionary tale. PMID- 2324517 TI - Laser-induced photodynamic therapy with aluminum phthalocyanine tetrasulfonate as the photosensitizer: differential phototoxicity in normal and malignant human cells in vitro. AB - Photodynamic therapy (PDT) involves the use of laser or noncoherent light energy with photosensitizing dyes to induce a cytotoxic reaction in the target cells, resulting in cell injury and/or death. In this study, we have examined laser induced phototoxicity in normal human skin fibroblasts and HT-1080 fibrosarcoma cells incubated with aluminum phthalocyanine tetrasulfonate (AlPcS) in vitro. The culture, laser, and photosensitizer parameters were varied in attempts to establish the conditions for differential cytotoxicity between normal and malignant human fibroblasts. Biochemical assays, as a measure of cytotoxicity, included [3H]thymidine incorporation (an index of DNA replication), [35S]methionine incorporation (a measure of protein synthetic activity), and the MTT assay (an indirect index of mitochondrial activity). In the absence of laser irradiation, AlPcS was non-toxic to both cell lines in concentrations up to 25 micrograms/ml. Laser light alone at 675 nm (the absorption maximum of AlPcS) had no effect on the cells at energy densities up to 16 J/cm2. In the presence of 3 or 10 micrograms/ml of AlPcS, both cell lines demonstrated marked energy dependent toxicity. If an 8-h or a 24-h "efflux" period in AlPcS-free medium was allowed to take place prior to laser irradiation, normal fibroblasts were much less sensitive to PDT, whereas fibrosarcoma cells still exhibited a marked degree of toxicity. The results indicate that, under appropriate treatment conditions, AlPcS is capable of preferentially sensitizing a malignant mesenchymal cell line, while sparing its non-malignant normal cell counterpart. PMID- 2324518 TI - Epidermal and dermal effects of epidermal growth factor during wound repair. AB - Epidermal growth factor (EGF), a well-characterized peptide that stimulates in vitro cell proliferation, has now been shown to enhance in vivo resurfacing of porcine wounds. Topical formulations containing either recombinant EGF or placebo were applied daily to partial-thickness wounds along the dorsal surface of pigs. Following full-thickness removal of these wounds, tissues were sectioned and stained, and histologic sections were subjected to computerized morphometric analysis. A significant acceleration of epithelialization across the wound surface was noted following daily EGF treatments. EGF delivered in a variety of topical formulations also produced a marked increase in the cellularity and thickness in the neodermis. A dose-responsive increase in the thickness of the granulation tissue was also observed. In conclusion, topical application of EGF stimulates epithelialization of partial-thickness wounds and produces a positive impact on the underlying dermis during the early phases of wound repair. PMID- 2324519 TI - Value of the cutaneous basophil hypersensitivity (CBH) response for distinguishing weak contact sensitization from irritation reactions in the guinea pig. AB - Numerous studies of the histology of allergic contact dermatitis reactions to potent allergens in guinea pigs and humans have indicated that there is significant tissue infiltration with basophilic leukocytes. In this study we determined whether this histologic finding could be of value in distinguishing weak sensitization reactions from primary irritation, thereby aiding in the predictive identification of weak or moderate contact allergens. Guinea pigs were sensitized by the Buehler test method. Skin reactions were graded 24, 48, and 72 h post-challenge with duplicate patch sites biopsied at the 24- or 72-h grading timepoints. The biopsies were fixed, embedded in glycol methacrylate, thin sectioned, and Giemsa stained. The number of basophils per 400 leukocytes were counted along the upper dermis just below the dermal/epidermal junction. Challenge patch sites from animals sensitized to a relatively low dose of the strong contact allergen, oxazolone, were compared with patch sites from animals challenged only with a strong irritant, sodium lauryl sulfate (SLS). Compared to normal skin (7.5 +/- 1.0 basophils/400 leukocytes +/- SEM) only the oxazolone patch sites showed significant basophil infiltration (36.8 +/- 6.5), despite the fact that the skin reactions to the low oxazolone challenge dose were relatively weak. SLS patch sites showed no basophil infiltration above normal skin levels (4.8 +/- 0.9). Subsequent blinded studies compared weak/moderate presumptive sensitization reactions (as defined by accepted visual skin grading criteria) to various chemicals (citronellal, vanillin, cinnamic aldehyde, and ethylenediamine) to primary irritation reactions to the same chemicals. In each case, low challenge-dose sensitization sites on previously treated (induced) animals showed mean basophil infiltration (range, 11.9-69.2 basophils/400 leukocytes) significantly greater than higher-dose irritant reactions (range, 1.6-13.3). The range for normal skin was 0.2-10.2 and the range for strong patch reactions to higher concentrations of oxazolone was 59.8-209.3. These data strongly indicate that light-microscopic quantitation of the CBH response can be used to distinguish relatively weak to moderate contact sensitization reactions from primary irritation reactions to the same chemicals. PMID- 2324520 TI - Site-specific suppression of cell-mediated immunity by cyclosporine. AB - In this study, it was demonstrated that site-specific suppression of T-cell mediated immune responsiveness could indeed be achieved by topical application of cyclosporine. Evidence for site-specific immune suppression was obtained from a dual skin allograft model in rats. These animals were given an initial 10-d systemic treatment of CsA. Subsequently, one allograft was treated with topical CsA and the other was treated with the vehicle alone. Anti-inflammatory efficacy and prolonged skin allograft survival were observed both grossly and histopathologically in the presence of topically administered CsA, while contralateral vehicle-treated control grafts underwent vigorous rejection. Systemic lymphocyte DNA synthesis following Con-A and PHA stimulation was normal to elevated. Therefore, systemic T-cell-mediated immunity appeared unaffected or possibly activated even with concomitant topical CsA treatment. CsA levels were low systemically, and showed relative site-specificity in terms of tissue concentration. In conclusion, this study indicates that topical CsA is capable of locally suppressing a strong T-cell-mediated immune response after an initial short-term systemic dose of CsA. Furthermore, certain putative autoimmune and inflammatory diseases of the skin, such as psoriasis and eczematous dermatitis, which may share common mechanisms of action compared to skin allograft rejection should likewise benefit from topical CsA treatment. PMID- 2324521 TI - Mechanisms of cyclosporine A inhibition of antigen-presenting activity in uninvolved and lesional psoriatic epidermis. AB - To elucidate how cyclosporine A affects antigen-presenting cell subsets and their function in human skin, we studied patients with psoriasis undergoing a therapeutic trial of cyclosporine A. Immunologic parameters abnormal in psoriatic epidermis were evaluated before and early in the course of therapy. We quantitated function and numbers of skin biopsy-derived epidermal cells with potential antigen-presenting cell (APC) activity. The antigen-presenting capacity of epidermal cells from normal-appearing skin to activate allogeneic T cells was profoundly inhibited (81% decrease) 7 d after the onset of therapy (p less than 0.05). Thus, cyclosporine A therapy inhibited T-cell activation mediated by Langerhans cells in uninvolved skin. By contrast, in lesional skin epidermal allo antigen presenting activity was only partially inhibited at this early time point (55 +/- 7% decrease) (p less than 0.01, n = 8). The percentage decrease in allo antigen-presenting cell activity correlated with reduced clinical activity of the lesions, r = 0.84. In three patients also examined at 14 d, we found an additional 42 +/- 5% decrease between day 7 and 14. Decreased allo-antigen presenting activity in lesional skin was not associated with a decrease in the number of CD1+ Langerhans cells or epidermal cell release of detectable amounts of cyclosporine A or other soluble factors that abrogate T-cell alloreactivity. The time course and degree of inhibition of antigen-presenting capacity within involved psoriatic skin correlated best with a significant (p less than 0.01) reduction in non-Langerhans cell DR+ leukocytes (from 3.0 +/- 1.2% to 1.0 +/- 0.6% at day 7) (r = 0.71). Cyclosporine A therapy was associated with a rapid and complete loss of HLe1-DR+ keratinocytes (94% decrease at 7 d) in lesional skin despite the skin still being quite involved with psoriasis at this point and antigen-presenting cell activity being only 60% reduced. In conclusion, cyclosporine A interferes with T-cell activation by human epidermis through at least two mechanisms: 1) in uninvolved skin, rapid inhibition of Langerhans cell mediated activation of T cells, and 2) in lesional skin, delayed inhibition of antigen-presenting activity which appears to correlate with the time course and level of reductions in non-Langerhans cell DR+ leukocytes. The antigen-presenting activity of the latter cells appears to be cyclosporine A resistant. In psoriatic lesions, early and complete loss of DR expression on lesional keratinocytes during cyclosporine A therapy is likely due to decreased lesional T-cell lymphokine production critical for keratinocyte DR expression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2324522 TI - Sensory characteristics of camphor. AB - The perceptual effects of camphor on hairy skin were measured in a psychophysical experiment. Subjects rated the intensity and quality of sensations produced when a solution of 20% camphor (in a vehicle of ethanol and deionized H2O) was applied topically to the volar forearm. Under conditions in which skin temperature was varied either from 33-43 degrees C or from 33-18 degrees C, it was found that camphor increased the perceived intensity of the cutaneous sensations produced during heating and cooling. Although camphor's effect appeared to be greater during warming, neither effect was large. Camphor also produced a significant increase in the frequency of reports of "burning." It is concluded that camphor is a relatively weak sensory irritant that may have a modest excitatory effect on thermosensitive (and perhaps nociceptive) cutaneous fibers. PMID- 2324523 TI - Genetic control of nickel sulfate delayed-type hypersensitivity. AB - Genetic control of delayed-type hypersensitivity (DTH) to nickel sulfate antigen was studied using various strains on inbred mice. Mice with class II Ad,k,s haplotypes showed a high magnitude of response, whereas those with class II Ab,f were low responders. These results indicate that nickel sulfate DTH may be influenced by the I-A region of H-2. Transfer experiments revealed that these responses might be mediated by L3T4+, Lyt-2- T cells. PMID- 2324524 TI - Expression of protein kinase C isozyme in epidermal Langerhans cells of the mouse. AB - Protein kinase C (PKC) is encoded by a complex of a gene family, and its multiple isozymes are expressed in various mammalian tissues. We examined whether PKC is expressed in epidermal Langerhans cells (LC) of the mouse by using monoclonal antibodies specific to PKC I, PKC II, and PKC III isozymes (respective products of PKC genes gamma, beta, and alpha). Immunohistochemical and immunoblotting studies revealed that LC of adult C57BL/6 mice express PKC II, while PKC I and PKC III were not detected. In keratinocytes, none of the isozymes were detected. These results suggest that PKC II is a novel marker of LC and that it possibly plays a regulatory role in epidermal LC of the mouse in vivo. PMID- 2324525 TI - Tumor necrosis factor alpha induces invasiveness of human skin fibroblasts in vitro. AB - The chemotactic response of fibroblasts plays an important role during wound healing and fibrosis. Several substances have been found to mediate fibroblast migration in vitro. In the tissue, however, fibroblasts have also the potential to pass through connective tissue barriers following a chemotactic stimulus. Since tumor necrosis factor alpha (TNF alpha) is a cytokine released by mononuclear cells during wound healing, we have been interested in studying its effect on the regulation of fibroblast chemotaxis and invasive migration. TNF alpha did not attract skin fibroblasts nor did it alter their chemotactic response towards other chemoattractants like fibroblast conditioned medium or fibronectin. However, whereas normal skin fibroblasts did not invade a collagen I gel, preincubation of the cells with TNF alpha markedly induced their invasive migration into the gel. This seems to be associated with a specific degradation of type I collagen, because TNF alpha did not promote the invasion of skin fibroblasts through a reconstituted basement membrane (Matrigel). PMID- 2324526 TI - Analysis of dose response of trinitrochlorobenzene contact hypersensitivity induction in mice: pretreatment with cyclophosphamide reveals an optimal sensitizing dose. AB - A detailed dose-response curve has been established for induction of contact hypersensitivity (CH) in mice with trinitrochlorobenzene (TNCB). It was determined that in BALB/c, CBA/J, and C57BL/6 mice, the dose required to sensitize via epicutaneous application was between 1 and 10 micrograms TNCB. When doses of hapten of 200 micrograms or greater were painted on abdominal skin, CH responses were induced which were only marginally greater than responses induced by sensitizing doses of hapten in the 10-50-micrograms range, implying that no further dose-response relationship exists beyond 50 micrograms of hapten. However, in companion experiments, in which panels of mice were pretreated with cyclophosphamide, it was determined that sensitizing doses of hapten in excess of 50 micrograms induced both CH and concomitant induction of down-regulation of CH. Thus, at 200 micrograms or higher doses of TNCB, CH responses of cyclophosphamide pretreated mice were invariably more intense than in their untreated, hapten painted cohorts. In the animals pretreated with cyclophosphamide, it was possible to see that a dose-response relationship continued to exist between the amount of epicutaneously applied hapten over a 200 micrograms to 14 mg range and the intensity of the CH induced. We conclude that the optimal dose for immunizing mice epicutaneously with TNCB is between 10 and 50 micrograms. This is considered optimal since animals sensitized in this manner display no evidence of concomitant down-regulation of their CH responses. PMID- 2324527 TI - All-trans retinoic acid stimulates growth and extracellular matrix production in growth-inhibited cultured human skin fibroblasts. AB - All-trans retinoic acid was examined for effects on human dermal fibroblast proliferation and for effects on fibroblast production and expression of non collagenous and collagenous components of the extracellular matrix in vitro. Fibroblast proliferation was blocked when the cells were cultured in the presence of a serum-free culture medium containing epidermal growth factor, hydrocortisone, insulin, ethanolamine, phosphoethanolamine, and bovine pituitary extract as growth supplements and 0.15 mM Ca++. This level of extracellular Ca++ is lower than that needed to support fibroblast growth. Under these conditions, growth was stimulated by all-trans retinoic acid. Proliferation was also stimulated in the same basal medium without the growth supplements. Growth promoting concentrations of all-trans retinoic acid ranged from 0.5-2.0 micrograms/ml (1.7-6.6 X 10(-6) M). Stimulation of proliferation was not seen at higher or lower concentrations. Concentrations of all-trans retinoic acid that stimulated proliferation also induced increased production of fibronectin as indicated by biosynthetic labeling/immunoprecipitation and by enzyme-linked immunosorbent assay. Increased production was associated with increased staining for fibronectin in the extracellular matrix. Increased production of two other non-collagenous extracellular matrix component, i.e., thrombospondin and laminin, also occurred in all-trans retinoic acid-treated cells. At 0.5 micrograms/ml, all trans retinoic acid also stimulated production of type I collagen by the dermal fibroblasts, but at higher concentrations (2.5 micrograms/ml) production of type I collagen was inhibited. These data indicate that all-trans retinoic acid can induce changes in dermal fibroblasts in vitro (i.e., increased proliferation and extracellular matrix production) that mimic the major changes seen in the dermis after topical treatment with this agent. PMID- 2324528 TI - Alkanes: endogenous or exogenous? PMID- 2324529 TI - Gamma delta T cell receptor-bearing lymphocytes during Epstein-Barr virus infection. AB - Lymphocytes bearing gamma delta T cell receptors (TCR) constitute a minor subpopulation of human peripheral blood lymphocytes. Their role and function during microbial infections are largely unknown. In 10 patients with Epstein-Barr virus-induced infectious mononucleosis, the gamma delta TCR-expressing T cell population expanded during the acute phase. These cells were largely delta TCS1-, CD4-, and CD8- but expressed activation antigens such as human leukocyte antigen DR and CD38. The convalescent phase of infectious mononucleosis was characterized by a relative persistence of gamma delta T cells. Together these data suggest a possible role of gamma delta T cells in the control of primary Epstein-Barr virus infection in humans. PMID- 2324530 TI - Comparison of bactericidal activity of five antibiotics against Staphylococcus aureus. AB - Ten volunteers were given each of five antibiotics, sequentially, until steady state was reached. Peak and trough sera were then drawn, and bactericidal titers were determined to two different isolates of Staphylococcus aureus, both sensitive in vitro to all antibiotics tested. The antibiotics were cephalexin, trimethoprim/sulfamethoxazole (TMP/SMZ), clindamycin, dicloxacillin, and ciprofloxacin. Mean peak serum bactericidal titers (SBT) were significantly higher for cephalexin than for dicloxacillin, ciprofloxacin, and TMP/SMZ (P less than .05). The difference between cephalexin and clindamycin did not achieve statistical significance. Dicloxacillin, clindamycin, and ciprofloxacin were not statistically different from each other. Mean SBT for TMP/SMZ was less than 1:2, significantly less than that achieved by the other antibiotics. Only clindamycin achieved a trough SBT greater than 1:2. This was statistically significant compared with each of the other antibiotics. PMID- 2324531 TI - Prevalence and clinical importance of Entamoeba histolytica in two high-risk groups: travelers returning from the tropics and male homosexuals. AB - This study was undertaken to learn the prevalence of amebiasis and to assess the clinical importance of Entamoeba histolytica in two high-risk groups: 2700 travelers returning from the tropics and 320 male homosexuals. Some 16.3% of the homosexual men and 4.0% of the travelers had E. histolytica infections. Only five travelers showed a pathogenic zymodeme of E. histolytica, which correlated closely with invasive amebiasis with positive amebic serology and clinical symptoms with diarrhea. The homosexual group had neither a pathogenic isoenzyme pattern nor positive amebic serology. Currently, travelers to the tropics have a risk of 0.3% (1:340) of acquiring invasive amebiasis; 92.5% of all E. histolytica infections in travelers remain asymptomatic and are confirmed by serology and zymodeme status. No homosexual presented with invasive amebiasis. PMID- 2324532 TI - Porphyria cutanea tarda as initial presentation of the acquired immunodeficiency syndrome in two patients. PMID- 2324533 TI - Detection of antibodies in late Lyme disease. PMID- 2324534 TI - Fatal hypoglycemia associated with Clostridium perfringens bacteremia. PMID- 2324535 TI - Prostatitis caused by Hansenula fabianii. PMID- 2324536 TI - Isolated meningitis caused by Blastoschizomyces capitatus. PMID- 2324537 TI - Reduction of free amphotericin B acute toxicity in mice after intravenous administration of empty liposomes. PMID- 2324538 TI - Evaluation of the infectivity, immunogenicity, and efficacy of live cold-adapted influenza B/Ann Arbor/1/86 reassortant virus vaccine in adult volunteers. AB - A cold-adapted (ca) influenza B reassortant that derived two genes encoding the hemagglutinin and neuraminidase from influenza B/Ann Arbor/1/86 wild-type virus and six internal RNA segments from ca influenza B/Ann Arbor/1/66 virus was evaluated in 66 adult volunteers having a serum hemagglutination inhibition antibody titer less than or equal to 1:8. The ca reassortant was attenuated and elicited the production of systemic and local antibodies; the 50% human infectious dose was 10(6.4) TCID50. Six weeks after vaccination, 12 unvaccinated volunteers and 13 recipients of ca virus (10(7.5) TCID50) were challenged experimentally with homologous wild-type influenza B virus. The ca vaccine completely protected against illness, and the magnitude of shedding was 50-fold less in vaccinees than in unimmunized controls, five of whom became ill. These findings indicate that the six internal RNA segments of the ca influenza B/Ann Arbor/66 donor virus confer desirable properties of a live virus vaccine to a reassortant derived from a virulent virus. Such reassortants may be suitable vaccines for healthy adults. PMID- 2324539 TI - Evaluation of the potency and safety of inactivated Japanese encephalitis vaccine in US inhabitants. AB - In 1981 and 1982, two US citizens died from Japanese encephalitis (JE) acquired in China. In 1983, the Centers for Disease Control initiated an evaluation of a purified, inactivated, mouse-brain-derived JE vaccine produced and used in Japan since 1966. Two doses of this vaccine given 1-2 weeks apart evoked neutralizing antibody titers greater than or equal to 8 in only 77% of recipients. After three JE vaccine doses administered 1-2 weeks apart, 99% developed titers greater than or equal to 8. When a third dose was given to 29 participants 6-12 months after the primary series, all developed titers greater than or equal to 16. Reported adverse reactions included injection site tenderness (18%), erythema (6%), or swelling (3%); headache (9%); and dizziness, fatigue, sleepiness, nausea, chills, fever, or lower back pain (less than or equal to 5%). On the basis of this study, three doses of BIKEN JE vaccine are recommended for US citizens who may be at risk of exposure to JE virus. PMID- 2324540 TI - The effect of number of exposures on the risk of heterosexual HIV transmission. AB - Several studies of the heterosexual transmission of human immunodeficiency virus have reported no association between transmission and number of exposures. In contrast, this study showed that for a susceptible sex partner, the number of exposures to an infected index case is indeed associated with transmission, but in a nonlinear fashion. Factors that can dilute an association between transmission and number of exposures include measurement error in calculating number of exposures, use of inappropriate statistical models, and failure to account for variations in transmission rates. For example, the practice of anal intercourse and the experience of bleeding during intercourse increase the likelihood of transmission. We also observed that transmission occurred with fewer exposures among couples who did not use condoms compared with couples who did. The number of exposures also affects the independent association between other risk factors and transmission and thus should be considered when analyzing other sources of risk. PMID- 2324541 TI - Risk of Haemophilus influenzae type b disease in children with cancer and response of immunocompromised leukemic children to a conjugate vaccine. AB - From 1969 to 1988, 8 cases of systemic Haemophilus influenzae type b (Hib) disease occurred among 5288 patients with cancer. For the first 4 years of life, systemic Hib disease was significantly greater in leukemic children than in the general population (606/100,000 vs. 90/100,000, respectively). Fifty children aged 2-6 years with acute leukemia were vaccinated with a Hib conjugate vaccine, ProHibit. The overall response rate was 50%; however, 75% of children receiving leukemic therapy for less than 12 months responded versus 18% of those treated longer. After vaccination, the geometric mean antibody concentration was 7.2 micrograms/ml, appreciably lower than for normal children of similar ages. After 12 months, the geometric mean antibody concentration had declined to 0.35 micrograms/ml, and 75% of subjects had antibody levels greater than or equal to 0.15 micrograms/ml. A booster dose for unsuccessfully vaccinated subjects was of minimal benefit. Children with acute leukemia in remission who were treated according to the leukemia therapy protocol of St. Jude Children's Research Hospital had a good likelihood of responding to the conjugate Hib vaccine if administered within a year of initiation of chemotherapy. PMID- 2324542 TI - Behavioral contributions to acquisition of gonorrhea in patients attending an inner city sexually transmitted disease clinic. AB - To begin to define the behaviors that influence gonorrhea acquisition, a case series of patients attending a sexually transmitted disease clinic was surveyed. Although gonorrhea rates were similar, men and women differed in sexual behaviors predictive of infection. Men with a new or casual partner were more likely to have gonorrhea than men with no such partners (adjusted odds ratio = 2.7); this finding did not hold true for women. Condom use in the previous month reduced the chances of gonorrhea acquisition for both men and women. More than 33% continued to engage in sexual activity after onset of symptoms or knowledge of sexually transmitted disease exposure. Individuals with repeated episodes of gonorrhea exhibited an array of risk-taking behaviors, such as intravenous drug use and casual sex partners. These data suggest the complex nature of the behaviors and sexual contexts within which gonorrhea acquisition occurs. PMID- 2324543 TI - A retrospective cohort study of nosocomial diarrhea as a risk factor for nosocomial infection. AB - Because most nosocomial infections are caused by enteric flora, it was undertaken to determine whether diarrhea predisposes to nosocomial infections by conducting a retrospective cohort study involving patients with and without nosocomial diarrhea who were hospitalized during a 12-month period. The rate of urinary tract infection per person-day after onset of diarrhea was significantly greater in patients with diarrhea (relative risk = 10.3; 95% confidence interval = 1.7 63.1, P = .006). When indwelling bladder catheter and duration of catheter placement were considered, diarrhea remained an independent risk factor for urinary tract infection in logistic regression analysis (P = .009). These data suggest that diarrhea and consequent urethral meatal contamination may be a cause of nosocomial urinary tract infection, especially in patients with a catheter, and that removal of the catheter should be considered whenever possible in patients with diarrhea. PMID- 2324544 TI - Toxic shock syndrome associated with Staphylococcus aureus sinusitis in children. AB - Toxic shock syndrome (TSS) is a severe, acute, multisystem illness associated with rash and shock. It is usually associated with a focal infection (e.g., during menstruation associated with tampon use, abscess, surgical wound infection) caused by certain Staphylococcus aureus strains. Identification and drainage of the focus of infection may be important in therapy. Occasionally, a focus of infection is not obvious, requiring additional diagnostic procedures. Three cases of children with TSS associated with sinusitis and no other focus of S. aureus infection are presented, demonstrating the important consideration of the perinasal sinuses as a cryptic focus of S. aureus infection causing TSS. PMID- 2324545 TI - Vancomycin-resistant Pediococcus acidilactici: nine cases of bacteremia. AB - Pediococci, vancomycin-resistant gram-positive cocci, have been isolated from human specimens, but an association with clinical illness has not been established. Clinical and epidemiologic data were obtained on nine patients who had Pediococcus acidilactici isolated from blood. Patients were eight elderly adults with complicated medical problems and one infant with congenital jejunoileal atresia. Seven patients were hospitalized before P. acidilactici was isolated. Eight had received multiple antibiotics; however, only two had received vancomycin. In all cases there was a delay in correct bacterial identification, and the significance of the isolate was uncertain. There was no clearly identified syndrome associated with P. acidilactici bacteremia. All eight adults had fever and six had pneumonia potentially attributable to other causes. The findings underscore the importance of proper identification of vancomycin resistant gram-positive cocci. P. acidilactici may be an opportunistic pathogen in severely compromised hosts; however, further observations are necessary to clarify its role in human disease. PMID- 2324546 TI - The association of Shiga toxin and other cytotoxins with the neurologic manifestations of shigellosis. AB - The neurologic symptoms in human shigellosis have often been attributed to Shiga toxin, although its exact role has not been determined. By use of a [3H] thymidine-labeled HeLa cell assay, cytotoxic activity was demonstrated in stool but not cerebrospinal fluid or serum from five patients with shigellosis presenting with seizures or encephalopathy. Bacterial isolates produced 16.0-88.2 CD50 (50% cytotoxic dose) of cytotoxin/mg of protein. The toxin activity in stool and the cytotoxic activity of the isolates were not neutralized by antiserum to purified Shiga toxin. DNA hybridization studies showed that Shigella isolates from these patients lacked the structural genes for Shiga toxin. The cytotoxin produced was also distinct from Shiga-like toxins I and II. Sonicates of the Shigella strains injected intraperitoneally into mice caused lethargy and lethality. The toxin activity was heat-labile and sensitive to trypsin, indicating that its active component is protein. Ultrafiltration and gel filtration chromatography showed a molecular mass of 100-125 kDa. Thus Shiga toxin production is not essential for the development of neurologic manifestations of shigellosis; other toxic products may play a role. PMID- 2324547 TI - Serologic diagnosis of pertussis: evaluation of pertussis toxin and other antigens in enzyme-linked immunosorbent assay. AB - IgM, IgA, and IgG antibodies to Bordetella pertussis were measured in paired sera from 34 patients who were culture-positive for pertussis by enzyme-linked immunosorbent assay (ELISA) with disrupted B. pertussis bacteria, purified pertussis toxin, or outer membrane proteins (OMP) as antigens. Paired sera from 50 patients with other respiratory infections were used as controls. The sensitivities of the assays from paired sera were 61%, 90%, and 90% and specificities were 98%, 92%, and 72%, respectively. Of the patients culture positive for pertussis, 68% had positive levels of antibody to pertussis toxin antigen in their first serum samples, obtained at the same time as samples for culture. Infants had antibody responses to pertussis toxin antigen, in contrast to weak antibody responses measured by B. pertussis antigen. The results from this study indicate that ELISA, especially measuring pertussis toxin IgA, is a valuable additional tool for diagnosing pertussis and can be used as a complementary test with cultures. PMID- 2324548 TI - A new semiquantitative culture method for early detection of surgical incisional wound infection. AB - A semiquantitative culture technique for early detection of surgical wound infection was done by rolling a segment of a plastic intravenous catheter across a blood agar plate after insertion into the most inflamed part of the wound on postoperative day 3. Patients were monitored daily for purulent discharge until healing. Of the 53 wounds studied, 44 (83%) had no growth or low-density superficial colonization on the blood agar (generally less than 15 colony-forming units and within the upper 1.5 cm of the catheter). None of these 44 wounds was subsequently infected; therefore, these colonies represented colonization. Of the 9 wounds (17%) that yielded greater than 15 colony-forming units and a diffuse subcutaneous pattern (colonies below the upper 1.5 cm of the catheter), all developed purulent discharge with a positive culture of the same organisms found by semiquantitative culture. This result differed significantly (P less than .01) from the 44 wounds without subsequent infection. This semiquantitative technique has the potential to distinguish infection from colonization and may be useful in diagnosing surgical wound infection. PMID- 2324549 TI - Serum tumor necrosis factor levels and disease dissemination in leprosy and leishmaniasis. AB - It has been suggested that tumor necrosis factor alpha (TNF alpha) may serve as an important antigen-independent host defense mechanism against parasitic organisms. Sera from 66 patients with leishmaniasis and 68 patients with leprosy, all from Ethiopia, were tested for TNF alpha using an enzyme-linked immunoassay. Sera from patients with the multi-parasitic/bacillary type of disease (visceral or diffuse cutaneous leishmaniasis and lepromatous leprosy), known to be associated with absent or low specific T cell response, contained significantly higher TNF alpha titers than those of patients with pauci-parasitic/bacillary disease (localized cutaneous leishmaniasis and nonlepromatous leprosy). High titers of TNF alpha in the absence of a functioning T cell response do not appear to confer resistance against Leishmania aethiopica and Mycobacterium leprae. PMID- 2324551 TI - Blood cell growth factors: their biology and clinical applications. Second International Capri Conference. October 8-12, 1989. Proceedings. PMID- 2324550 TI - A serodiagnostic assay by microenzyme-linked immunosorbent assay for human anisakiasis using a monoclonal antibody specific for Anisakis larvae antigen. AB - A serodiagnostic assay system to detect human anisakiasis is described. This assay uses a microenzyme-linked immunosorbent assay with monoclonal antibody An2 that recognizes the antigen specifically found in Anisakis simplex larvae. The data showed that sera from infected patients reacted strongly with the A. simplex larvae antigen that was immobilized with monoclonal antibody An2 on microplates. Patients' IgG, IgA, IgM, and IgE reacted strongly with An2-defined antigen at 4 or 5 weeks and at 1 or 7 days, respectively, after the onset of clinical symptoms of anisakiasis. However, sera from healthy persons did not react, even though they often ate raw fish. This indicates a high diagnostic specificity of this assay system for clinically manifested anisakiasis. PMID- 2324552 TI - Partial purification and characterization of human megakaryocyte colony stimulating factor (Meg-CSF). AB - Megakaryocyte colony-stimulating factor (Meg-CSF) in urinary extracts from patients with aplastic anemia was partially characterized and purified. Using Meg CSF-enriched fractions, we established that the moiety has the following characteristics: 1) portions of the molecules having Meg-CSF activity have sialic acid, probably with a biantennary structure, and beta-galactose residues as the terminal and penultimate sugars; 2) disulfide residues are an essential chemical group of the molecule and are located on its surface; and 3) Meg-CSF activity is stable in n-propanol, but not in acetonitrile with trifluoroacetic acid. Partial purification of Meg-CSF by a four-step procedure of ethanol precipitation, CM Affi-Gel Blue chromatography, wheat germ agglutinin-sepharose chromatography, and high-resolution hydroxyapatite chromatography, yielded a concentrate with a 430- to 630-fold increase in specific activity. The partially purified Meg-CSF fractions stimulated both human and murine megakaryocytopoiesis in vitro (CFU meg). When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreduced conditions, Meg-CSF activity was recovered in the 29-34 kDa molecular weight fractions. We have also shown that Meg-CSF, purified from the urine of aplastic anemia patients, stimulated murine megakaryocytopoiesis and platelet production in vivo. Final purification of human urinary Meg-CSF is currently in progress. PMID- 2324553 TI - Cell interactions and gene expression in early hematopoiesis. AB - As part of an investigation of the mechanisms controlling gene expression during lineage commitment, we have investigated the transcriptional status of hematopoietic lineage-specific genes and the interactions of early hematopoietic progenitor cells with stromal cells of the marrow microenvironment. The results indicate that a subset of otherwise lineage-restricted genes are transcriptionally active and/or DNAse I hypersensitive (i.e., "primed" for transcription) in multipotent, interleukin 3-dependent hematopoietic cells, and that they may become inaccessible and transcriptionally silent when cells are induced to adopt a single lineage during commitment. The external influences regulating gene expression in hematopoietic cells include binding interactions with stromal cells and exposure to locally presented growth factors. These interactions are thought to be essential for hematopoietic cell development and may be dysregulated in chronic myeloid leukemia. PMID- 2324554 TI - Interleukin 6 and its receptor in the immune response and hematopoiesis. AB - Interleukin 6 (IL-6) plays critical roles in the immune response and hematopoiesis. It is a potent B cell differentiation factor inducing antibody forming plasma cells. It enhances interleukin 3-induced proliferation of hematopoietic stem cells. Furthermore, IL-6 induces maturation of megakaryocytes. In IL-6 transgenic mice, a massive polyclonal plasmacytosis and an increase in the number of mature megakaryocytes in the bone marrow were observed. The data indicated that deregulated expression of the IL-6 gene induced a polyclonal plasmacytosis and could be involved in the oncogenesis of plasma cell neoplasias. IL-6 receptor (IL-6R) was molecularly cloned and found to be an immunoglobulin superfamily having an MW of 80 kDa. Upon the binding of IL-6 to its 80 kDa IL-6R, a second non-binding molecule, gp130 was shown to associate with IL-6R. The complex of IL-6 and soluble IL-6R lacking both transmembrane and cytoplasmic domains could bind gp130 and transduce the signal. The results indicate that the IL-6R system consists of two polypeptide chains: one is an 80 kDa ligand-binding molecule and the other is a possible signal transducer, gp130. PMID- 2324555 TI - Sensitivity of erythroid progenitors to recombinant growth factors in the diagnosis of myeloproliferative disorders. AB - Sixty-six adults were studied with the aim of establishing positive diagnostic criteria for myeloproliferative disease. Erythroid colony formation from peripheral blood progenitors was assayed in a serum-free culture system with the addition of recombinant human growth factors. Endogenous colonies were more frequent in myeloproliferative disease than controls. The mean number of clusters per erythroid burst (BFU-e) in cultures with erythropoietin only was lower in primary proliferative polycythemia (polycythemia vera, PPP) than controls. In PPP, primitive BFU-e demonstrated greater dependence on interleukin 3 than controls, and mature BFU-e more susceptibility to inhibition by alpha-interferon. The findings indicate an abnormal response to several different cellular messengers in PPP, and permit an effective diagnostic discrimination from non clonal polycythemias. PMID- 2324556 TI - Pain description by nurses and physicians. AB - The purpose of this study was to determine if nurses and physicians selected similar words to describe painlike experiences and to determine how they rated terms commonly used to describe pain. Thirty-seven registered nurses and 21 physicians comprised the sample. The Visual Analogue Scale (VAS) was used to measure the terms ache, hurt, and pain. The McGill Pain Questionnaire (MPQ) provided a list of word descriptors from which the subjects selected words that best represented the terms ache, hurt, and pain. There was no significant differences between the nurses and physicians in the mean rating of any of the pain terms on the VAS. The nurses and physicians chose very similar word descriptors from the MPQ to discriminate one pain term from another. These findings suggest that nurses and physicians may have a common understanding of the language used to describe painlike experiences. PMID- 2324557 TI - Epidural versus intrathecal morphine-bupivacaine: assessment of consecutive treatments in advanced cancer pain. AB - Twenty-five patients with multifocal and multitype (somatic, visceral, and neurogenic) advanced cancer pain who experienced severe pain despite extradural (ED) morphine and bupivacaine were converted to intrathecal (IT) morphine and bupivacaine. The consecutive ED and IT periods (2-174 days, median = 50 days, and 1-305 days, median = 37 days, respectively) were assessed in clinical terms (daily analgesic dosages giving acceptable pain relief and quality of life expressed as sleeping hours and walking/daily activities). With the IT treatment, the total (all routes) opiate consumption and the daily doses of spinal morphine and spinal bupivacaine decreased significantly at the beginning of the treatment compared to the ED period, and continued to be significantly reduced for up to 1 wk for spinal opiate and bupivacaine and 6 mo for total opiate. The spinal opiate and bupivacaine doses were still lower in 50% of the patients at the end of the IT treatment compared to the end of the ED period. When final ED versus initial (2nd day) IT doses were assessed, the daily median dose ratios were 7.5 for total opiate and 4 for both spinal opiate and bupivacaine. Subsequently, lower daily volumes and higher concentrations were needed for IT administration of the drugs. During the first month of the IT treatment, sleeping and walking scores improved compared to ED treatment. Thus, the IT treatment gave more satisfactory pain relief, and--because of lower daily doses and volume--proved to be more suitable for treatment at home (continuous infusion from external pumps) than the ED treatment. PMID- 2324558 TI - Cancer pain management according to WHO analgesic guidelines. AB - On admission to a pain management unit, 92.5% of 174 cancer patients suffered from more than moderate pain despite prior treatment. This inefficacy was mainly due to underdosage of drugs, inadequate intake schedule, and hesitation to use strong opioids. Following introduction of an oral drug therapy based on World Health Organization (WHO) guidelines, more than 80% of all patients described their pain as ranging between "none" and "moderate" on a six-step verbal rating scale at all times. To obtain these results, it was necessary to adapt the therapy to increasing pain in the course of terminal disease. Step III (strong opioids) gained more and more importance with time, and step I (nonopioids) was finally useful only in a minority of patients. Side effects played a minor role as a reason to change therapy. Oral drug therapy following these guidelines led to sufficient pain control in most patients over the whole study period (7,400 days); only 11% of the patients required other methods of pain management. PMID- 2324559 TI - Subarachnoid and epidural calcitonin in patients with pain due to metastatic cancer. AB - Nine patients with metastatic cancer who had pain refractory to traditional treatments received a subarachnoid injection of salmon calcitonin. Eight of the nine patients reported pain relief after subarachnoid injection varying from 1 hr to 5 days. Four of the responding patients subsequently received an epidural injection of salmon calcitonin, and two of these patients reported pain relief. Although many patients experienced pain relief, nausea and vomiting appeared to be a significant side effect, occurring in seven out of nine patients. PMID- 2324560 TI - Clinitron therapy and pain management in advanced cancer patients. AB - Many patients with advanced malignancy develop bone metastases, pathologic fractures, and skin breakdown, all of which compromise comfort and interfere with the delivery of patient care. In 1986, 38 Clinitron beds were utilized at Calvary Hospital, a specialty hospital for advanced cancer, for patients who were immobile and/or had significant pain. Twenty-five patients were entered into an open study to assess and document this experience. Twenty-two patients experienced improved comfort while Clinitron therapy was in use. Global questionnaires relating to pain, comfort, appetite, and sleep were completed by the patients, their primary nurses, and attending physicians. No adverse effects were noted. The results suggest that Clinitron therapy is effective in promoting comfort in select advanced cancer patients. The difficulties encountered in research in this patient population are presented. PMID- 2324561 TI - Referred otalgia. PMID- 2324562 TI - Narcotic-induced pulmonary edema. PMID- 2324563 TI - Management of a patient with osteoradionecrosis of the mandible with nerve blocks. PMID- 2324564 TI - Psychologic distress of chronic pain sufferers and their spouses. AB - Recent research has begun to document the relationship between chronic pain and psychologic distress among pain patients, yet little attention has been given to the spouses' reaction to the chronic pain condition. The results of this research using the Symptom Checklist-90 (SCL-90) to assess the psychologic distress among both chronic pain sufferers and spouses (61 couples) reveal elevated distress scores among both groups when compared with the norms from a nonpatient sample. Patients and spouses present similar profiles according to the SCL-90 subscales, with patients' scores significantly higher on the somatization, hostility, and psychoticism subscales. No differences by sex were found. PMID- 2324565 TI - National and international regulation of opioid drugs: purpose, structures, benefits and risks. AB - The established international and national drug control systems have been successful in preventing diversion from legitimate producers of opioids to illicit channels. This has contributed to a reduction of opioid abuse and related illegal activities. However, the systems have fostered concepts and attitudes that have limited access to opioid drugs, which the international treaties recognize are indispensable for the reduction of pain and the treatment of other conditions. Patients who have a legitimate need for the relief that these drugs can provide have become the unintended victims of the drug control systems. PMID- 2324566 TI - [64th meeting of the Japanese Association for Infectious Diseases. Matsuyama, 19 21 April 1990. Abstracts]. PMID- 2324567 TI - Fractionated hyperthermia in vivo: thermotolerance, sensitivity to BCNU and thermochemosensitivity in the BT4An rat glioma. AB - Although hyperthermia has been shown to increase the effect of some cytotoxic drugs both in vitro and in vivo, there is sparse data on the interaction of the two modalities during fractionated treatment in vivo. In vitro data suggest that, parallel to development of thermotolerance, tumour cell sensitivity to drugs may be modified. Thermotolerance in tumour and surrounding normal tissue and the sensitivity to the alkylating agent BCNU given alone i.p., or as thermochemotherapy, was investigated in the subcutaneously transplanted BT4An rat glioma. Tumours treated by 44 degrees C water bath hyperthermia alone minutes after the priming hyperthermia were initially sensitive to hyperthermia, but decreased heat sensitivity developed during continued heating. Thermotolerance in the skin was greatest at 24 h. When the skin reaction was compared with the effect on tumours, a therapeutic gain using hyperthermia alone was seen at 168 h. Tumours were most sensitive to BCNU just after the priming hyperthermia, least sensitive at 48 h. When thermochemotherapy with BCNU was given at different intervals after priming hyperthermia, an interaction between the modalities was seen, with the greatest tumour effect just after priming (six of 12 tumours controlled). At 24 h the summary effect of priming treatment and subsequent thermochemotherapy was not greater than thermochemotherapy treatment alone. The thermochemotherapy effect on tumours was more dependent on the hyperthermia sensitivity, i.e. thermotolerant state, than the sensitivity to BCNU alone at that time. PMID- 2324568 TI - Effects of local hyperthermia on natural killer activity in mice. AB - The effect of local hyperthermia on natural killer (NK) activity in C3H mice was investigated, because there have been reports on both the enhancing and suppressing effects of hyperthermia on NK activity. When right hind legs of mice were treated at 43 degrees C for 45 min, NK activity was first suppressed. It reached its lowest level 2 days after the treatment, then recovered, and was significantly enhanced on the 7th day. When mice were treated at a lower temperature (41 degrees C), NK activity was enhanced even 2 days after the treatment. In addition, the suppression of NK activity, which was observed 2 days after the treatment at 43 degrees C, was diminished to some extent by i.p. injection of liposomal recombinant human superoxide dismutase (L-r-hSOD). From these results it is suggested that local hyperthermia had an enhancing effect on NK activity, which plays an important role in the anti-tumour mechanism of hyperthermia, and that transient suppression of NK activity after hyperthermia at 43 degrees C was partially cancelled by the administration of L-r-hSOD. PMID- 2324569 TI - Thermotolerance of the spinal cord after fractionated hyperthermia applied to the rat in the cervical region. AB - The effects of heat treatment at 42.9 +/- 0.4 degrees C for 30-90 min of rat cervical spinal cord (cervical 5-thoracic 2) were investigated in animals which had received a priming treatment at 42.3 +/- 0.4 degrees for 60 min in the same region 24 hours before. Hyperthermia to the cervical region in the rat was applied by a coaxial double ring radiator, operating at a frequency of 434 MHz. The test heat treatment led to neurological complications, ranging from unco ordinated use of the forelegs to paralysis of both forelegs. Death was observed, presumably as a result of respiratory paralysis. The animals that received the priming heat treatment were more resistant to heat injury than those without priming. The LD50, 60 days, for animals without and with priming treatment was respectively at 41 +/- 2 min 42.9 degrees C and at 88 +/- 7 min 42.9 degrees C. The TTR calculated from the LD50, 60 days, data is 2.1 +/- 0.2. Almost all animals, without priming, that did not die as a result of the treatment, recovered in the period from day 1 to day 60 after hyperthermia. Animals that had received a priming exposure were less able to recover from neurological symptoms induced by the test heat treatment. For this reason the induced resistance to thermal injury after priming exposure was more pronounced in the data on lethality than on neurological symptoms. Spinal cord histology from animals that did not recover from neurological symptoms showed extensive non-vascular damage to both gray and white matter. PMID- 2324570 TI - Blood perfusion measurements in human tumours: evaluation of laser Doppler methods. AB - Laser Doppler flowmetry is a simple method of determining, directly and continuously, tissue blood flow. However, its applicability to monitoring tumour blood flow interstitially during hyperthermia treatments is still being evaluated. The purposes of this study were to physically characterize the measurement probes, to evaluate potential sources of artifact with the interstitial use of the probes during hyperthermia treatment, and to obtain measurements in human tumours during hyperthermia sessions. The accuracy of the method in quantifying blood flow, velocity and volume during hyperthermia was found to be unaffected by heating the measurement probe to 42-46 degrees C or by exposing it to various intensities of 915 MHz microwave fields (10-40 W), or 1 MHz ultrasound fields. Catheter insertion methods were developed to place the flow probes interstitially in tumours. Tissue damage was confined to a distance of no greater than 0.12 mm away from the catheter tract, and physical evidence of vascular disruption was within a distance of 0.05 mm as measured in a rat tumour model. This degree of damage/disruption is unlikely to affect LDF measurements which represent blood flow averaged over a 1.0-1.5 mm radius from the probe tip. Concurrently, the device was used to monitor tumour blood flow parameters interstitially in human subjects during hyperthermia treatments given in combination with conventional radiotherapy. Blood-flow data from multiple sites of measurement showed marked heterogeneity within individual tumours (up to 55 fold differences) and between different tumours (greater than 100-fold differences). Measurements made by translating the probe along a tumour radius, beginning at the tumour core and advancing to the tumour edge, were consistent with a two-component tumour perfusion model (shell and core). Data are presented from one patient illustrating a persistent change in perfusion distribution during the hyperthermia treatment course, which occurred concomitantly with increases in thermal data. These results suggest that the technique might be of value in monitoring change in flow between treatments. Responses during hyperthermia treatment sessions were also investigated. Four temporal patterns of flow were observed, ranging from a steady increase in flow to a plateau level to a steady drop in flow during heating. These patterns were not well correlated with average temperature recorded at the site of flow measurement. Further study is needed to determine if this LDF technique is to be useful for evaluation of heat transfer by blood perfusion. PMID- 2324571 TI - A comparison of temperatures in canine solid tumours during local and whole-body hyperthermia administered alone and simultaneously. AB - Temperature measurements were made in canine solid tumours during whole-body hyperthermia (WBH) alone, local hyperthermia alone and local hyperthermia given simultaneously with WBH. During the plateau phase of WBH alone, mean intratumoral temperature ranged from 41.3 +/- 0.2 degrees C to 41.7 +/- 0.1 degrees C and was statistically lower (P = 0.0028) and more variable than rectal temperature, which ranged from 42.0 +/- 0.02 degrees C to 42.1 +/- 0.03 degrees C. The temperature distribution in solid tumours during WBH is more uniform than during local hyperthermia. The simultaneous administration of whole-body and local hyperthermia in five dogs resulted in increased tumour temperatures in comparison to WBH and in more uniformly increased tumour temperatures in comparison to local hyperthermia alone. Median intratumoral temperatures (+/- 95% confidence intervals) resulting from local hyperthermia alone and local hyperthermia given simultaneously with WBH were 39.9 degrees C (39.7-40.1) and 42.9 degrees C (42.6 43.1), respectively, and were statistically different (P = 0.0012). Local applied power requirements to meet predetermined intratumoral temperature limits were decreased by 50% (P = 0.011) in dogs undergoing combined local/whole-body hyperthermia versus local hyperthermia alone. Dogs tolerated the combination of local and WBH without complication. PMID- 2324572 TI - Thermal dosimetry of spinal cord heating in the mouse. AB - Three systems for the localized heating of the spinal cord of the mouse have been evaluated by measuring the temperatures in the spinal canal (Tsp); at a reference location dorsal to the spine (Tdo), and by numerically calculating temperature distributions throughout two-dimensional transverse cross-sections through the middle of the heated region. The systems assessed were water bath heating alone, water bath-rf combination and rf heating alone with oblique, dorsally located electrodes. It has been established that (1) for all systems delta T (where delta T = Tdo-Tsp) decreased throughout a 1 h heating period-this was attributed to changes in blood flow; (2) there existed a considerable variation in the experimental value of delta T, particularly for rf heating. The resulting error in the estimation of Tsp from a measured value of Tdo can be reduced by making use of the observed correlation between delta T and the slope of a temperature decay curve measured at the beginning of the heating period; (3) rf alone best spares adjacent visceral and superficial tissues from significant elevation of temperature. PMID- 2324573 TI - Comparison of numerical calculations with phantom experiments and clinical measurements. AB - Three-dimensional models, while fundamentally desirable in hyperthermia treatment simulation, are only beginning to emerge and may take a number of years to perfect for routine clinical use. Two dimensional calculations, on the other hand, can be efficiently performed on today's inexpensive computer workstations; however, the accuracy of two-dimensional models in the pretreatment planning context is questionable. This paper investigates the ability of a general two dimensional finite element model to predict power deposition patterns in phantoms and temperature distributions during actual clinical treatments. The experiments and simulations have been performed for an annular phased array (APA) operating at 70 MHz. Comparisons between model predictions and measurements show that quantitative agreement occurs in phantoms containing moderate complexities in heterogeneity, but that only qualitative agreement appears possible in clinical treatments. However, the results suggest that the lack of blood flow information may contribute as much, if not more, to the uncertainties in the clinical predictions than the two-dimensional nature of the model itself. PMID- 2324574 TI - Pre-focal plane high-temperature regions induced by scanning focused ultrasound beams. AB - A steady-state, three dimensional, bioheat transfer equation-based simulation program has been developed and used with single and multiple transducer arrangements to investigate the effects of spherical transducer characteristics (frequency and f-number) and scanning patterns on treatment temperature distributions. Results for uniformly perfused tissues show that: (1) a single circular scan induces radially non-uniform temperature distributions at the focal depth and undesirable pre-focal high temperature regions; and (2) multiple circular scans spaced by the focal diameter of the ultrasound beam and using feedback control can induce uniform temperature distributions in the focal plane, but still cause undesirable pre-focal plane high temperatures. These two results apply both to a single transducer scanned with its axis normal to the skin and to multiple tilted transducers with overlapping foci. The extent and magnitude of this pre-focal high-temperature region increases as frequency increases (from 0.5 to 2.0 MHz) and as the f-number increases (from 1.0 to 2.0). Finally, (3) when four tilted transducers with overlapping foci are used with multiple circular scans spaced by the focal diameter, if the transducer closest to the central axis of the scans is turned off (every transducer is turned off periodically) the pre focal high-temperature region can be eliminated. From the results of this parametric study and practical considerations, a reasonable compromise of transducer choice for general use is one with a low f-number (about 1.0) and a frequency of about 1.0 MHz. For multiple tilted transducers with overlapping foci the choice of frequency is also 1.0 MHz and the f-number should be as low as possible. PMID- 2324575 TI - Use of heating rate and specific absorption rate in the hyperthermia clinic. AB - The specific absorption rate (SAR), which is the mass-normalized rate of energy absorption by a biological body, has been used by hyperthermia researchers to characterize energy deposition and heating patterns in tissues and in biological models. Before thermal diffusion and blood flow alter the temperature distribution, energy deposition and heating rate (HR) are related by constants. Therefore SAR is usually calculated from the initial rate of temperature rise measured during heating. SAR is an appropriate parameter for theoretical calculations or electric field measurement in tissue. However, the ultimate parameter in hyperthermia is temperature. Instead of computing the temperature rise from SAR (W/kg) and specific heat (kcal/kg.degree C) which were originally obtained from temperature measurements, it is simpler and more convenient to use HR (degree C/W-min) directly, especially when heterogeneous tissues are involved. The advantages of using HR instead of SAR in hyperthermia clinics are discussed. PMID- 2324576 TI - Catheter induced temperature artifacts in ultrasound hyperthermia. AB - Temperature artifacts were evaluated at 72 different sensor locations in 10 different tumour sites heated by use of planar ultrasound transducers operated at 1 and 3 MHz. Thermometry was carried out by single- and multisensor thermocouple probes inserted into 19- and 16-gauge polyurethane catheters, respectively. Nearly all catheters were oriented approximately perpendicular to the ultrasound beam. The artifacts were determined by backward extrapolation of the thermal decay 30-60s after the power was turned off. The effective blood flow and specific absorption rate (SAR) at the sensor locations were determined from the rate of decay and the steady-state temperature. The sample mean steady-state temperature, effective blood flow, and SAR were 41.4 degrees C, 17.5 ml/100 g/min, and 46.3 W/kg, respectively. The most frequent artifact was in the range 0 0.2 degrees C and the mean artifact was 0.6 degrees C. Less than 15% of the artifacts were above 1 degree C. The magnitude of the artifact correlates with the SAR of ultrasonic power, the effective blood flow rate, and the steady-state temperature. These results indicate that the artifact produced at 1 MHz by a multisensor, Teflon-sheathed thermocouple inserted into a 16-gauge polyurethane catheter is 1.7 +/- 0.4 degrees at an SAR of 100 W/kg. PMID- 2324577 TI - Temperature artifacts produced by thermocouples used in conjunction with 1 and 3 MHz ultrasound. AB - The relative temperature artifacts produced by a selection of commercially available thermocouples and catheters were evaluated in radiation bolus and beef phantoms heated by 1 and 3 MHz continuous ultrasound. The thermocouples included a 23 gauge needle microprobe inserted directly into the phantoms, polyurethane sheathed, Teflon-sheathed, and exposed-tip thermocouples, each inserted into a 19 gauge polyurethane closed-end catheter, a multisensor Teflon-sheathed probe inserted into a 16 gauge polyurethane catheter and a Teflon-sheathed single sensor probe without a catheter. The needle microprobe and the polyurethane sheathed thermocouple produce equivalent artifacts. The artifacts produced by the Teflon and exposed-tip thermocouples are 1.4 +/- 0.3 times greater, that produced by the multisensor Teflon-sheathed probe is 2.1 +/- 0.3 times greater, and that produced by the Teflon-sheathed thermocouple without a catheter is 2.3 +/- 0.4 times greater. The results in the beef phantom indicate that the needle microprobe and polyurethane-sheathed thermocouple both produce artifacts of 0.7 +/- 0.1 degree in tissue at an SAR of 100 W/kg. PMID- 2324578 TI - The concentric-ring array for ultrasound hyperthermia: combined mechanical and electrical scanning. AB - While two-dimensional phased arrays can be electronically focused and steered in three dimensions without physically moving the applicator, they generally require a relatively large number of small transducer elements and, consequently, complex drive electronics. A configuration that does not require a large number of elements is that of a concentric-ring array. The field conjugation method can be used to produce a focal spot (or multiple spots) along the array axis. The resulting focal regions are very small and need to be steered transversely to heat tumours of typical size. However, steering the focused beam away from the array axis results in annular heating patterns which are often associated with undesired secondary foci (hot spots). In this paper, a method based on combining electrical and mechanical scanning using a concentric-ring applicator is presented. Advantages of the new method over the mechanically scanned fixed-focus transducers, currently in use, are pointed out. Computer simulations are conducted to investigate the possibility of heating different size tumours by appropriately combining the two scanning techniques. The bioheat transfer equation is solved numerically and temperature distributions associated with relevant heating patterns are presented and discussed. The simulations demonstrate the possibility of the combined technique to produce useful heating patterns which cannot be produced by either technique separately. PMID- 2324579 TI - Preliminary studies of interstitial hyperthermia using hot water. AB - A hot water interstitial hyperthermia unit was used to heat normal tissue in the thighs of rabbits and pigs. A 4 x 4 array of metal needles or plastic tubes spaced at 10 or 14 mm was implanted. Temperature measurements were made using five-sensor thermocouple probes inserted parallel to the implanted needles or tubes. With a water temperature of 48 degrees C, tissue temperature within the implant exceeded 42.5 degrees C when tube spacing was 14 mm and reached 47 degrees C when the spacing was 10 mm. However, at the lower water temperature of 45.5 degrees C inter-tube spacing was more critical, since the tissue temperature was above 43.5 degrees C for a spacing of 10 mm but below 42.5 degrees C for a spacing of 14 mm. Temperatures observed in vivo tended to be higher than those predicted by computer simulations, in which blood flow was assumed to be greater than that of resting muscle i.e. approximately greater than 0.45 kg m-3 s-1. The results show that an interstitial system using hot water can be a simple and efficient method of inducing hyperthermia. PMID- 2324580 TI - SAR distribution of the 'coaxial TEM' system with variable aperture width: measurements and model computations. AB - An extensive comparison between measured and computed heat absorption distributions in several phantoms inside the 'coaxial TEM' applicator is presented. The influence of the width of the aperture and of the presence of a PVC tube is especially considered. PMID- 2324581 TI - Experimental assessment of phased-array heating of neck tumours. AB - An investigation of phased-array microwave systems (PAMS) for non-invasively inducing hyperthermia, primarily in neck lesions, has been done with implications for applications at other sites such as lung and pelvis. Our general approach was to combine numerical and analytical approaches with parallel experimental studies. In this paper we will concentrate only on the experimental aspects. The object, such as a homogeneous cylindrical phantom or a neck phantom, was encircled with several standard applicators driven by a single source, but with relative phase and amplitude control over each applicator. The relative phases of the applicators were adjusted by using an implanted monopole antenna connected to an HP network analyser. Power was applied and the specific absorption rate (SAR) was determined by using split phantoms and thermography or by measuring temperature transients dT/dt, recorded by implanted thermometer probes. We found that at 915 MHz for our applicators (SMA Co.) the centre of an 11 cm diameter muscle-like phantom heated to about 33% of the value at the surface in front of the applicator. Similarly, we were able to show significant SAR at the centre of realistically sized neck phantoms using four phased apertures of 915 MHz. Furthermore, substantial improvement was observed if the frequency was lowered to about 400 MHz. PMID- 2324582 TI - [An overview of breast cancer mass screening in Japan]. AB - To establish the effective mass screening projects for the breast cancer, our study group cosponsered by the Welfare Ministry was organized by 11 regional groups. From 1968 to 1986, 643, 513 women at the initial screening and 719, 189 women at the subsequent screening were examined by physical examination. Out of them, abnormalities were present in 24, 864 women (3.9%) and 23,880 (3.3%), respectively. A detection of cancer was made in 833 women (detection rate 1.3%) and 428 women (0.6%), respectively. As the examinees increased from year to year, the subsequent examinees were over the initial ones. It was suggested that most of examinees had been fixed year by year and the detection rate of initial screening had been higher than that of the subsequent one. Then more initial examinees are expected to be increased. Women 30 to 59 years of age were mostly screened, but women aged 60 or more should be increased. Of women with abnormal physical findings, women over 90% took the second examination. But more effective, economical and safer screening instruments are expected to be developed and be used at the first examination. PMID- 2324583 TI - [Prophylactic therapy for liver metastasis of gastrointestinal carcinomas using biological response modifiers (BRM): fundamental studies on the inhibition of experimental liver metastasis by intraportal administration of OK-432]. AB - For prophylactic therapy to inhibit hepatic metastatic recurrence after surgical treatment of gastro-intestinal carcinomas, the effects of OK-432, a biological response modifier (BRM), were examined with inoculation of tumor cells and administration of OK-432 via portal vein. Experiments with the inhibition of liver metastasis were performed as follows. The animals were divided into five groups. Group 1: 1.0 KE of OK-432 was given intraportally 5 minutes after injection of 5.0 X 10(6) tumor cells per rat via the portal vein. Group 2: Non medicated group, only 5.0 X 10(6) tumor cells per rat were injected into portal vein, as the control for group 1. Group 3: 0.5 KE of OK-432 and 2.5 X 10(6) tumor cells per rat were used. Group 4: 1.0 KE of OK-432 and 2.5 X 10(6) tumor cells were used. Group 5: Non-medicated group, injected with 2.5 X 10(6) tumor cells as the control group for groups 3 and 4. Colonies of metastases in the liver of each group were examined by autopsy on the 30th day after treatment. Metastases were observed in 75% of group 1, 100% of group 2, 58.8% of group 3, 64.3% of group 4 and in 90% of group 5. For the investigation of the mechanisms to inhibit these liver metastases, 51Cr labeled AH60C tumor cells were injected into the portal vein, and the remained of radioactivity in rat liver was examined. The result showed that OK-432 injected into the portal vein did not directly kill the lodging tumor cells. To prove the morphological evidence of inhibition of hepatic metastasis, the changes of tumor cells were microscopically observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324584 TI - [Clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in a patient with acute non-lymphocytic leukemia with two CNS recurrences]. AB - A case of two repeated CNS recurrences of acute non-lymphocytic leukemia (M2) was treated with intermediate dose Ara-C therapy and achieved 2 complete remissions. The clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in this patient were discussed. A 55-year-old male with acute non-lymphocytic leukemia (M2) achieved complete remission by combination chemotherapy of Behenoyl ara-C, Daunorubicin, 6-Mercaptopurine and Prednisolone in July, 1985. He subsequently received consolidation and intensification therapy with periodical intrathecal injection of Methotrexate (MTX), but 13 months later he developed his first CNS recurrence which was resistant to the intrathecal administration of Ara C and MTX. As he also relapsed systemically, Ara-C was administered in intermediate dose (1 g/m2 every 12 hrs for 5 days) and he achieved complete remission both in the CNS and systemic manifestations. Six months later he was diagnosed as having a second CNS recurrence and another systemic relapse. Intermediate dose Ara-C was administered again, and he achieved complete remission in the CNS and partial remission in systemic manifestations. Pharmacokinetic study revealed high peaks of Ara-C concentration in plasma (6.2 microM immediately after the end of the infusion) and high degree of its penetration into the CNS (5.6 microM at 3 hr after the end of the infusion) suggesting the effective and perhaps a uniform level of Ara-C is achieved throughout the CNS by this therapy. In 3 other patients without CNS involvement 0.88 +/- 0.44 microM of Ara-C, which is enough concentrations for its cytostatic effect, was detected at 3 hr after the end of infusion, suggesting the efficacy of the therapy for CNS prophylaxis. In this case the relapse occurred after repeated administration of antileukemic drugs, including Behenoyl-ara-C, an analog of Ara-C, and was resistant to the intrathecal administration of Ara-C. These findings suggest that intermediate dose Ara-C therapy was effective to overcome a resistance to antileukemic drugs, including Ara-C, and also, in some cases, more effective than intrathecal injection of antileukemic drugs for the treatment of CNS leukemia. PMID- 2324585 TI - [Antitumor responses after reinfusion of autologous plasma perfused over immobilized protein A: a study in patients at advanced stages of cancer]. AB - Four patients at advanced stages of cancer (Pts.#1 and #4; breast adenocarcinoma, Pt.#2; rectal adenocarcinoma, and Pt.#3; adenocarcinoma possibly originated in the pancreas) received reinfusions of plasma perfused over protein A columns (IMURe Corporation; Seattle, Wa., U.S.A.). The treatment schedule was essentially the same as was reported by "the Protein A Clinical Trial Group" (Messerschmidt, G. L., et al.). Twice a week, patients received 230-250 ml of protein A-treated plasma. No other anticancer modality was employed. Pt.#1 received only one treatment due to increased general malaise. Pts.#2 and #4 completed 12 and Pt.#3 received 13 plasma-therapies. General malaise on the day after plasma return was a common untoward effect, which usually disappeared spontaneously in 48 hours. Pt.#2 experienced chills during the first two plasma returns. Pt.#3 complained dyspnea at the 6th treatment. Otherwise, no serious adverse effect was observed. No remarkable changes were obvious in the profile of daily blood chemistry. Tumor ulcerated to the chest wall in Pt.#1 appeared to be dried and, in parts, to be edematous or have reduced the size 16 hours after the first plasma therapy, while no changes were obvious in the skin adjacent to the tumor. In Pts.#2 and #4, there appeared to be tumors were isolated at palpation. Ascites was reduced in Pt.#3. Increases in tumor markers were retarded in Pts.#2 (CEA) and #4 (CA15-3). CA19-9 in Pts.#3 and #4 did not increase during the perfusion therapy. Histology of tumor obtained from Pt.#4 six weeks after completion of the protocol revealed disruption of the tumor structure, necrosis of the tumor cells and increased deposit of fibrous materials. No objective reduction in the tumor sizes was achieved in any of the patients, and the overall result was "PD". It appeared to be full of suggestions, however, that the autologous plasma in such amounts of 230 ml or 3,000 ml did, after extra-corporeal manipulation, cause some changes in the tumor as were revealed by macroscopic and microscopic observations. PMID- 2324587 TI - [Clinical results of loco-regional hyperthermia combined with chemotherapy in the treatment of malignant tumors]. AB - From December 1982 through January 1989, 22 patients with 25 tumors were treated by thermochemotherapy. Of the 25 tumors, 13 were locally recurrent tumors after radiotherapy, 10 distant metastases, and 2 peritoneal disseminations. Employing two types of heating devices (8MHz capacitive RF, 430MHz microwave), hyperthermia was administered once or twice weekly, for 30-60 minutes per session, up to total sessions of 2-15 (mean = 6.9). In some sessions, anticancer drugs were administered intravenously or intraarterially immediately before or simultaneously with hyperthermia. Of the 25 tumors treated, 2 (8%) showed CR, 11 (44%) PR, 7 (28%) NC, and 5 (20%) PD. The better the tumor response was, the higher local control rate was achieved. The survival rate of patients who achieved CR or PR was higher than that of patients who showed NC or PD. Tumor volume, depth of tumor, averaged maximum intratumor temperature, the number of effective heat sessions and the number of anticancer drugs used were shown to affect the tumor response by multivariate analysis. On the other hand, averaged minimum intratumor temperature and history of previous treatment did not affect the tumor response. As almost all the tumors treated were considered to be refractory to radiotherapy or chemotherapy, the tumor responses obtained with thermochemotherapy seemed very encouraging. The expanded trials are warranted to reveal the effectiveness of thermochemotherapy. PMID- 2324586 TI - [The clinical significance of antibody against oncofetal antigen-I in patients with gynecologic tumors]. AB - Oncofetal antigen-I (OFA-I) is a membrane antigen of human cancer cells that cross-reacts with fetal brain tissues. OFA-I has been shown to be immunogenic in man by its ability to provoke humoral antibody in cancer patients which has tumoricidal potential with in vitro and in vivo experimental systems. This study evaluated the antibody profile against this antigen in relation to the course of disease. Twenty seven out of 39 patients with gynecologic tumors had persistently stable antibody levels and antibody titer in six of them increased by more than 4 fold. These patients did not show either recurrence or death, but had a good prognosis. In twelve patients, antibody levels dropped by more than 4-fold and was followed by clinical recurrence and death. These studies show that persistently stable antibody titers are predictive of non-recurrence, and decreasing titers predictive of recurrence. PMID- 2324588 TI - [Clinical evaluation of patients with relapsed prostatic carcinoma]. AB - A retrospective clinical study of 41 patients with prostatic carcinoma relapsing after endocrine therapy at Wakayama Medical College from 1972 to 1987 was reported. Patient's age was from 51 to 80, with an average of 69.8 years. Initial clinical stage was A in 2 patients, C in 12, D in 26 patients and unknown in one. Pathological grade at the first visit was well-differentiated cell type in 4 patients, moderately differentiated in 13, poorly differentiated in 23 patients and unknown in one. Of 41 patients, 32 had a local progression and 26 had an appearance or progression of metastasis. Several factors which might be related to the interval between initial endocrine therapy and relapse were analysed. Following factors such as poorly differentiated cell type, stage D, high Gleason score and increase in acid phosphatase level were revealed to be related to the short interval. Chemotherapy consisting of various agents and their combination has not been able to improve the survival of the patients with relapsed prostatic carcinoma. 1-year survival rate of all cases after relapse was 41.3% and none of the patients survived over 3 years. PMID- 2324589 TI - [SDI test using MTT for the evaluation of drug sensitivities of gastrointestinal cancer cells]. AB - The Succinic Dehydrogenase Inhibition test (SDI test) has been widely used for a long time to evaluate the sensitivities of cancer cells to anticancer agents. Recently, the techniques for tissue culture have progressed and the ability to make formazan improved through the use of MTT in this assay instead of TTC. Therefore, we modified SDI test in order to evaluate the drug response of gastrointestinal cancer and applied it in a clinical study. For the modification of the assay, we found it necessary to culture the cancer cells for three days and bring those cells in contact with MTT over a period of one hour. When we examined the sensitivities to anticancer agents at four different drug concentrations, if the cells were sensitive to the drugs, the optical densities were reduced according to the elevation of the drug concentrations. Further, we measured the drug concentrations in the blood of nude mice after the administration of anticancer drugs in the subrenal capsule assay which we developed previously. The drug concentration levels in the mice indicate the adequate drug dosage necessary to be effective in SDI test. PMID- 2324590 TI - [New combined therapy of radiation and local administration of OK-432 for esophageal cancer--local control rate and two-year survival rate]. AB - We devised new combination therapy of radiation and local administration of OK 432 and performed for 26 patients with esophageal cancer between March, 1987 and December, 1988 as a pilot study. The average age was 73 years. Among 26 patients, male were 20 and female were six. Patients were irradiated at the schedule of under 2 Gy/day and the dose of TDF (time, dose and fractionation factor) 100 totally. OK-432, 10KE was endoscopically administered around cancer lesion at the beginning of the radiotherapy, and two weeks later, 5KE was given in the same manner. Complete response was obtained 20 out of 26 cases (77%) and partial response was obtained in the remaining six cases (23%). All six patients with tumor length less than five cm showed complete response. All 16 patients who could not eat food orally before treatment, became to take food enough orally after the treatment and could discharge in good condition. One year and two years survival rate of 26 patients by Kaplan Meier method were 67.4% and 47.2%, respectively. Six patients with tumor length less than five cm, are all alive without a sign of recurrence. This combination therapy will improve not only the response rate and the survival rate, but also the quality of life of patients with esophageal cancer. PMID- 2324591 TI - [Effect of concomitant use of anticancer drugs and a Ca2+ antagonist, on human gastric cancer transplanted into nude mice]. AB - We examined the effect of concomitant use of anticancer drugs such as Carmofur or 5-FU and Nicardipine, a Ca2+ antagonist, on human gastric cancer transplanted into nude mice, and obtained the following results: 1. Combined administration of Carmofur or 5-FU together with Nicardipine caused potentiation of an antitumor effect. 2. After Carmofur was used together with Nicardipine, the FU level in the tumor tissue was significantly elevated. In conclusion, it was found that in the combined use of Carmofur or 5-FU together with Nicardipine, a Ca2+ antagonist, caused a higher level of the FU in tumor tissue and potentiation of an antitumor effect on human gastric cancer transplanted into nude mice. PMID- 2324592 TI - [A case of amphetamine poisoning manifesting rhabdomyolysis and reversible cardiomyopathy]. PMID- 2324593 TI - [Four cases in two families of hereditary progressive dystonia with circadian rhythm]. PMID- 2324594 TI - [A case of asymptomatic pheochromocytoma]. PMID- 2324595 TI - [A case of type II Bartter syndrome with prominent bilateral kidney calculi]. PMID- 2324596 TI - [A case of pulmonary alveolar calculi complicated by lung aspergillosis]. PMID- 2324597 TI - [Etiology and physiopathology of essential hypertension]. PMID- 2324598 TI - [Frequency of various types of secondary hypertension and pathogenic mechanisms]. PMID- 2324599 TI - [Prognosis of hypertension in Japan and its complications]. PMID- 2324600 TI - [Diagnostic criteria in hypertension--blood pressure determination]. PMID- 2324601 TI - [General considerations in the treatment of hypertension]. PMID- 2324602 TI - [The best time to begin and reduce the administration of antihypertensive agents in order to achieve an optimum blood pressure level]. PMID- 2324604 TI - [Treatment of hypertension complicated by coronary diseases and post-infarction hypertension]. PMID- 2324603 TI - [Treatment of hypertension complicated by diabetes mellitus and obesity]. PMID- 2324605 TI - [Treatment of hypertension complicated by cerebrovascular diseases]. PMID- 2324606 TI - [Treatment of hypertension complicated by kidney disorders and pregnancy toxemia]. PMID- 2324607 TI - [Clinical significance of blood pressure at the time of the office visit and at home and 24-hour blood pressure monitoring]. PMID- 2324608 TI - The case for oxidants in the adult respiratory distress syndrome--"elementary, Dr. Watson". PMID- 2324610 TI - A fish oil diet preserves renal function in nephrotoxic serum nephritis. AB - Fish oil diets preserve renal function in murine lupus, but we have found that these diets accelerate renal deterioration in renoprival nephropathy. In this study we examined the effects of dietary fish oil in accelerated nephrotoxic serum nephritis. For 1 month, 14 female rats were fed diets that differed only in fat composition, containing either menhaden (fish) oil or beef tallow (control). Rats were then preimmunized with rabbit IgG and, 5 days later, were injected with nephrotoxic serum. Glomerular filtration rate (GFR) was measured continuously in conscious animals by means of intraperitoneal 14C-labeled inulin minipumps. Fish oil-containing diets markedly attenuated the nephrotoxic serum-induced decline in GFR and the rise in proteinuria and significantly reduced glomerular prostaglandin E2 and thromboxane A2. The results of tests of renal histology showed no differences between the two groups. Five days after preimmunization, rats fed fish oil had more rabbit IgG remaining in their serum and had mounted less of an antibody response to the rabbit IgG. Fish oil diets also resulted in an attenuated disappearance of injected 14C-labeled rabbit IgG. In vitro, peritoneal macrophages from rats fed fish oil took up less rabbit IgG than macrophages from rats fed control diets. Thus the beneficial effects of a fish oil diet may result from defective immune surveillance and from alterations in eicosanoids. PMID- 2324609 TI - Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome. AB - Oxidative stress has been implicated in the adult respiratory distress syndrome (ARDS). In this study, we determined the levels of selected antioxidants in the plasma of 25 patients with ongoing ARDS and 16 healthy control subjects. We also examined these plasmas and pulmonary edema fluid of ARDS patients for lipid hydroperoxides. Both ascorbate and ubiquinol-10 concentrations in ARDS plasma were significantly lower than in normal plasma. alpha-Tocopherol concentrations, when standardized to total plasma cholesterol, were not lower in ARDS patients than in normal subjects. A pattern of antioxidant levels virtually identical to that observed in ARDS plasma was obtained after in vitro incubation of healthy plasma with stimulated polymorphonuclear leukocytes: very low ascorbate, decreased ubiquinol-10, and unchanged alpha-tocopherol concentrations. Nanomolar concentrations of lipid hydroperoxides were found in pulmonary edema fluid of ARDS patients, but not in plasma, nor in the plasma of healthy individuals, when a sensitive and selective chemiluminescence assay for hydroperoxides was used. ARDS patients also showed significant decreases in plasma levels of cholesterol esters in conjunction with discoidal high-density lipoprotein profiles, indicating a decrease in lecithin-cholesterol acyltransferase activity. We conclude that ARDS is associated with oxidative stress, possibly exerted by oxidants released from activated phagocytic leukocytes, and major changes in plasma cholesterol metabolism. PMID- 2324611 TI - Reduced arterial ketone body ratio during laparotomy: an evaluation of operative stress through the changes in hepatic mitochondrial redox potential. AB - The present article discusses the evaluation of surgical stress on the basis of the hepatic functional capacity of each patient. The changes in arterial blood ketone body ratio (KBR; acetoacetate/beta-hydroxybutyrate), which reflects hepatic mitochondrial redox potential, following intraoperative procedures were investigated in 60 laparotomy cases, including 30 cases with partial hepatectomy. The time course of changes in KBR was obtained by serial measurement during operation. The total area below the KBR level of 0.7 was defined as the hepatic stress score (HSS). HSS was significantly greater in the cases with hepatectomy (43.5 +/- 9.1; mean +/- SE) than in others (16.5 +/- 4.2; p less than 0.01). HSS in 13 patients accompanied by postoperative complications (60.4 +/- 17.7) was also significantly greater than that in the patients with uneventful postoperative courses (22.1 +/- 4.3; p less than 0.05). The former was also accompanied by significantly larger postoperative catabolic response preceding the clinical onset of complications (p less than 0.001). In the cases with uneventful postoperative courses, analysis of variance revealed that nitrogen balance and catabolic index in the first postoperative week were dependent on HSS negatively and positively, respectively (p less than 0.005), indicating a causative relationship between the suppression of hepatic energy metabolism during operation and the enhanced postoperative catabolic response. These results suggest that total surgical stress in major laparotomy can be quantitated and evaluated through the magnitude of decrease in hepatic mitochondrial redox potential, and that this evaluation may provide valuable information for intraoperative and postoperative patient care. PMID- 2324613 TI - Not the p value but the practice has the last word in the search for the truth. PMID- 2324612 TI - Hepatocytes express blood coagulation factor XII (Hageman factor). AB - The liver synthesizes blood coagulation factor XII (Hageman factor). The specific cell that expresses factor XII, however, has not been previously identified. We used primary rat hepatocytes cultured in serum-free medium to study the transcription, de novo synthesis, and secretion of factor XII. A 32P-labeled human factor XII complementary DNA probe was used for RNA blot hybridization. A single band of hybridization at 2.4 kilobases appeared in blots of polyadenylated RNA derived from 24-hour hepatocyte cultures. This corresponds to the known size of factor XII-processed primary transcript (messenger RNA). Cultured hepatocytes secreted labeled factor XII when tritiated leucine was added to the medium, indicating that the hepatocytes used 3H-leucine to synthesize factor XII de novo. In these hepatocyte cultures immunoreactive factor XII levels progressively increased in 24 hours and factor XII clotting activity increased in parallel. Cycloheximide inhibited the accumulation of both immunoreactive and coagulant factor XII. Secreted factor XII from the rat hepatocytes comigrated with authentic rat plasma factor XII at 80,000 molecular weight in a Western immunoblot. These data indicate that cultured hepatocytes transcribe, synthesize, and secrete authentic factor XII. PMID- 2324614 TI - Audiological manifestations of Ramsay Hunt syndrome. AB - Ramsay Hunt syndrome is known to cause audiological signs and symptoms, including sudden, unexpected hearing loss. We carried out a retrospective review of the audiological manifestations of 186 patients with Ramsay Hunt syndrome, measuring their hearing loss patterns, hyperacusis, tinnitus, herpetic rash, facial paralysis, pain and vertigo. Statistical correlations of these parameters were equated with prognosis. Prognosis for eventual hearing recovery is, in general, excellent. Prognostic indicators of poor hearing recovery include advanced age, retrocochlear hearing loss, male gender, vertigo, and speech frequency hearing loss. PMID- 2324615 TI - Treatment of earache among the Lappish people. AB - The traditional ways of treating earache among the Lappish people have been charted. Generally speaking, the Lapps have treated earache by applying a compress to the ear, dropping various ear-drops into the external auditory canal, breathing into the ear, massaging the ear, and inserting impregnated wool into the ear canal. The Lappish treatment principles for earache are discussed in relation to modern knowledge of pain relief. PMID- 2324616 TI - Critical evaluation of Per-Lee tubes in children. AB - A retrospective view of 37 Per-Lee tubes inserted into 29 patients over a period of four years. At the time of review all the tubes were in situ but eleven had to be removed due to recurrent otorrhoea or perforations causing increasing deafness particularly in children. Per-Lee tubes are not suitable for long-term ventilation of the middle ear cavity in children. PMID- 2324617 TI - Role of tympanic neurectomy in otalgia. AB - Tympanic neurectomy was first described 44 years ago. Although its indications have subsequently increased, it has not become a popular procedure. This paper concentrates on its use in treating otalgia. The history of tympanic neurectomy, the anatomy of the tympanic plexus and the aetiology of otalgia with specific reference to the tympanic plexus are discussed and a case of bilateral otalgia due to glossopharyngeal neuralgia successfully treated by staged, bilateral tympanic neurectomy reported. It is suggested tympanotomy performed under local anaesthesia with selective stimulation of the intra-tympanic nerves may lead to accurate diagnosis and treatment of the various forms of neuralgic otalgia. PMID- 2324618 TI - Rhinomanometry evaluation of the effects of pre- and post-operative SMR on exercise. AB - Nasal airway resistance due to uncomplicated DNS was examined in 43 patients, and the results compared with those obtained following corrective surgery. The patients were examined independently by the two authors using a strict examination protocol. Rhinomanometry was carried out pre- and post-operatively at rest and after exercise assessing the worst and the better breathing nostrils separately. The results show that both resting and post-exercise nasal resistance was reduced following septal surgery. PMID- 2324619 TI - Radiation induced tumours of the pharynx--can they be avoided? AB - Three patients who developed a post-cricoid carcinoma 5-21 years after radiotherapy for carcinoma of the larynx are presented. These patients received radiotherapy when they were young. It is suggested that alternative forms of treatment, especially partial laryngectomy with the aid of a laser should be considered in the primary management of small tumours of the larynx of young patients. PMID- 2324620 TI - Value of middle ear inflation as a diagnostic indicator of eustachian tube patency. AB - The value of tubal inflation as a diagnostic procedure for Eustachian tube patency and function is controversial. In an attempt to assess the diagnostic value of air douche in atelectatic ears, 49 such ears of 40 patients were politzerized. The procedure was successful in 45 ears. However, of the four unsuccessful cases, two of the patients were able to autoinflate their ears. These results show that air douches pass regularly through the Eustachian tube into the tympanic cavity even in atelectatic ears, which by definition suffer from aeration deficiency, which is often considered to be secondary to 'Eustachian tube obstruction', or alternatively 'Eustachian tube dysfunction'. Thus, the ability to force air through the Eustachian tube by politzerization is of no diagnostic value as an indicator of normal or abnormal tubal patency or functioning in atelectatic ears and most probably in allied conditions. PMID- 2324621 TI - Osteochondroma of the tongue. AB - A case is described of osteochondroma of the tongue and the literature on osteomata, chondromata and osteochondromata of the tongue is reviewed. The tendency for these tumours to arise in the region of the foramen caecum has been noted in previous reports as has the female preponderance. It has been suggested that they arise from remnants of branchial arch cartilage. The variation in the duration and age at presentation of the lesion has not been explained and an alternative theory is suggested. PMID- 2324622 TI - Per-oral excision of a branchial cyst. AB - The treatment of branchial cysts is by surgical excision. We describe a case where the cyst was medial to the pharyngeal constrictors, making a per-oral approach the safest, and easiest method of removal. The position of the cyst supports the theory that branchial cysts are congenital in origin. PMID- 2324623 TI - Unusual laryngeal cyst. AB - We report a lateral saccular cyst of the larynx with both an internal and external component. The patient had a four year history of a cervical swelling and hoarseness. He presented acutely with stridor. The cyst was resected successfully without tracheostomy. PMID- 2324624 TI - Basal cell adenocarcinoma of the parotid gland. AB - A case of basal cell adenocarcinoma of the parotid gland is reported. Histologically it is to be distinguished from basal cell adenoma and adenoid cystic carcinoma. Clinically the presentation may appear benign. Surgical excision is the treatment of choice. The prognosis is uncertain because of lack of follow-up data. PMID- 2324625 TI - Blindness: a potential complication of bilateral neck dissection. AB - Permanent blindness, is a very rare, but devastating complication of simultaneous bilateral neck dissection. Most otolaryngologists/head and neck surgeons are unaware that amaurosis can result from this surgery, and this paper is meant as a poignant reminder of that end. A case report is presented, followed by a discussion of possible aetiology; a management protocol is proposed. PMID- 2324626 TI - Large retropharyngeal cold abscess in an adult with respiratory distress. AB - A rare case of an adult with a large retropharyngeal cold abscess completely obstructing the airway and causing acute respiratory distress is presented. An urgent tracheostomy to safeguard the airway was required. The clinical features, surgical anatomy, aetiopathogenesis and management of a retropharyngeal abscess are discussed. PMID- 2324627 TI - 'Silence in court': twenty-one years of otolaryngology litigation. PMID- 2324628 TI - Appropriate attitudes to tympanometry. PMID- 2324629 TI - Pathology of the otic capsule. AB - The otic capsule is unique in retaining calcified cartilage, known as globuli interossei, throughout life and shows changes consequently, which are peculiar to it. In Paget's disease of bone, the otic capsule appears resistant to involvement and this occurs with extensive disease at a late stage. In contrast, otosclerosis is a new bone formation of unknown cause that is limited to the otic capsule. In osteogenesis imperfecta, the poor formation of collagen leads to abnormally thin bony trabeculae with a poorly formed otic capsule. In osteopetrosis, the otic capsule is greatly expanded by increased globuli interossei, as a result of defective osteoclast function. When fractured the middle layer of the otic capsule does not form callus, but heals by fibrosis. PMID- 2324630 TI - Pars flaccida perforation in tissue culture: morphological study. AB - Subtotal pars flaccida perforation was effected in vitro in rat tympanic membranes. The drums were subsequently kept in tissue culture and after various intervals studied by means of light and scanning electron microscopy. No complete covering of the perforation was seen, though a marked thickening and hyperplasia of the outer, keratinizing, squamous epithelium (OE) was evident. The inner, tympanal epithelium (IE) appeared swollen, containing rounded structures in the cytoplasm especially close to the contact area with the OE. Ingrowth of OE onto the tympanal side of the drum was seen particularly in the areas where the IE was sparse and completely lacking. Complete covering of a drum perforation seems to be dependent on the formation of supporting granulation tissue, probably resulting from an inflammatory reaction in the healing area. PMID- 2324631 TI - Hearing loss and Waardenburg's syndrome: implications for genetic counselling. AB - Ten families in which there were 79 individuals affected by Waardenburg's syndrome were examined for penetrance of sensorineural hearing loss and expressivity of the gene. There were 47 with Waardenburg syndrome Type 1 and 32 with Waardenburg syndrome Type II. Penetrance of senorineural hearing loss was calculated after exclusion of the probands and was found not to be significantly different between each syndrome type but to show marked interfamilial variation. A bilateral sensorineural hearing loss was present more frequently than unilateral with the proportion varying between families. Certain audiometric shapes were found to recur in the syndrome but, apart from possibly one asymmetric configuration, seem to have been described also in other conditions. The degree of hearing loss was very variable within and between families. The implications for genetic counselling are discussed and the advantages of basing risk factors upon individual families rather than syndrome types emphasized. PMID- 2324632 TI - Employment outcomes and social integration of students with mild handicaps: the quality of life two years after high school. AB - The employment outcomes and social adjustment of mildly handicapped students were examined in a sample of 65 randomly selected youths who exited high school in 1984. Personal and telephone interviews were conducted to obtain current employment data such as income, employment and training history, and use of community and social services in securing employment. Postschool social adjustment data included marital status, place of residence, types and frequency of social activities, friendship patterns, and satisfaction with social life. Seventy-eight percent of the respondents were employed. The majority worked on a full-time basis for minimum wage or better, were satisfied with their jobs, and relied on a self-family-friend network to secure employment. The majority of respondents were single, resided at home, and engaged in a variety of social activities on a regular basis. When the employment and social activity variables were combined, it was found that over 60% of the respondents were employed and held positive perceptions of their social life. PMID- 2324634 TI - The effectiveness of two methods for teaching a constraint-seeking questioning strategy to students with learning disabilities. AB - This study investigated the relative effectiveness of two methods of teaching an efficient questioning strategy to students with learning disabilities. The methods compared were (a) cognitive modeling alone in the use of constraint seeking questions, and (b) cognitive modeling and verbalization in the use of constraint-seeking questions, involving explicit and consistent instruction and feedback. Sixty subjects with learning disabilities were assigned randomly to one of these two conditions (n = 30 in each group). A pretreatment and posttreatment design was employed, with the criterion variable being number of questions required to obtain the correct answers to two 20 questions games. Results indicated that both groups showed significant reductions from pretreatment to posttreatment in the number of questions required. The two methods of instruction did not differ significantly in effectiveness. PMID- 2324633 TI - An approach to assessing and facilitating causal language in adults with learning disabilities based on Piagetian theory. AB - Salient characteristics associated with Piagetian cognitive stages served as the basis for developing a linguistic taxonomy of causal semantic relations. Causal statements from adults with learning disabilities and normally achieving adults were analyzed and organized within this taxonomy. A relationship between Piagetian cognitive stages and verbal expressions of causality was identified. Based on this relationship, principles of Piagetian cognitive theory were used to design assessment and intervention plans for adults with learning disabilities. PMID- 2324635 TI - Mainstreaming modification preferences of parents of elementary-age children with learning disabilities. AB - One hundred twenty-nine parents of children with learning disabilities responded to a questionnaire designed to solicit information on the types of modifications deemed most facilitative of parents' acceptance of full-time mainstreaming. Responses indicated that parents' participation in the mainstreaming process was an important factor in successful integration of children with learning disabilities. Parents' preferences for mainstreaming modifications differed from their current options, and they were supportive of full-time mainstreaming for their children, contingent upon implementation of their mainstreaming-related recommendations. Results are discussed relative to mainstreaming and proposed educational reforms. PMID- 2324636 TI - Phonological awareness tasks as predictors of decoding ability: beyond segmentation. AB - The performance of 38 male third- and fourth-grade reading disabled/poor decoders and above-average readers/good decoders was compared on a series of six measures of phonological awareness, including tasks that required the ability to segment, blend, and manipulate phonemes. Performance on these tasks was also correlated with phonetic decoding of pseudowords. Significant but varying intercorrelations were obtained among tasks in both groups. For the poor decoders, deletion was the most highly correlated with the other tasks. However, all good decoders performed at ceiling level on this task. For the poor decoders, deletion was significantly correlated with phonetic decoding (r = .74 and r = .78 for timed and untimed decoding measures, respectively). While all good decoders had good phonological awareness, not all those with good phonological awareness were good decoders. The results suggest that tasks that require blending and manipulation of phonemes, in addition to segmentation, may predict decoding ability best. PMID- 2324637 TI - Perception of gated, highly familiar spoken monosyllabic nouns by children with and without learning disabilities. AB - A forward-gating procedure employing highly familiar monosyllabic words was used in auditory testing of age- and gender-matched children with learning disabilities and normally achieving children aged 8 to 11 years. The portion of the word presented, or "gate," was longer on each successive trial. Nondisabled children identified an average of one more word than the children with learning disabilities, but the mean duration required for word identification did not differ between groups. Better receptive vocabulary scores were associated with identification of words at shorter durations only among the children with learning disabilities. The two groups of children had similar numbers of different meaningful-word and different non-word incorrect responses. The children with learning disabilities exhibited poorer fine-grained auditory discrimination than a control group of nondisabled children. The study concluded that auditory closure skills for the gating task were as good among children with learning disabilities as among nondisabled children, but that sensory discrimination problems may contribute significantly to the learning difficulties of the former group. PMID- 2324638 TI - First impressions formed of boys with learning disabilities and attention deficit disorder. AB - The present study examined the first impressions that are formed of boys with either learning disabilities (LD), attention deficit disorder (ADD), or both disorders, in an effort to understand better why they are so often unpopular with and rejected by their peers. The intent of the study was to remedy methodological problems of previous first-impression studies to determine whether devaluation of boys with either LD or ADD after a brief exposure is a reliable and valid finding. To this end, physical attractiveness data were gathered, children were employed as judges, subgroups of stimulus children were formed, and situational demands were varied. Results indicated that the boys with either LD or ADD were devalued relative to controls on a variety of dependent variables, including popularity. Both situational demands, as well as judgments of physical attractiveness, appeared to play a role in accounting for these differences. PMID- 2324639 TI - Cognitive correlates of social perception in students with learning disabilities. AB - In investigating possible explanations for social skills deficits in students with learning disabilities, researchers have examined social perception-the interpretation of behavior in order to understand the thoughts and feelings of others. This study specifically examined cognitive correlates of social perception in individuals with learning disabilities. Thirty-two students with learning disabilities in elementary grades were measured on three subtests (Comprehension, Picture Arrangement, and Digit Span) of the Wechsler Intelligence Scale for Children-Revised and on the Profile of Nonverbal Sensitivity. Both Picture Arrangement and Comprehension seemed to have an inherent relation to social perceptual functioning. Implications of these results are discussed. PMID- 2324640 TI - Demographic characteristics and mean profiles of Learning Disability Index subsets of the standardization sample of the Wechsler Intelligence Scale for Children-Revised. AB - The Learning Disability Index (LDI) was validated by an examination of the mean profiles and demographic characteristics of high and low LDI subsets of the standardization sample of the Wechsler Intelligence Scale for Children-Revised. The LDI continuum, however, was found to measure Third Factor strengths/weaknesses as much as verbal-performance discrepancies. PMID- 2324641 TI - 13-cis-retinoic acid is an endogenous compound in human serum. AB - The occurrence of 13-cis-retinoic acid as an endogenous component in human serum has been confirmed by cochromatography with standards in both normal-phase and reverse-phase high-performance liquid chromatographic (HPLC) system, by the lambda max of its UV spectrum recorded simultaneously with the HPLC run, and by chromatography of its methyl derivative. The method using solid-phase extraction followed by a gradient reverse-phase HPLC procedure with an internal standard and sensitive UV detector, provides an efficient and sensitive technique for the separation and quantification of serum 13-cis- and all-trans-retinoic acid. Serum levels of 13-cis- and all-trans-retinoic acid in 26 fasting volunteers ranged from 1.0 to 2.2 ng/ml (mean +/- SEM = 1.4 +/- 0.3 ng/ml) and from 1.1 to 1.9 ng/ml (mean +/- SEM = 1.4 +/- 0.2 ng/ml), respectively. The levels determined by a liquid-liquid double-phase extraction method were 90% higher in both 13-cis- and all- trans-retinoic acid than those from a solid-phase extraction. Human small intestine can isomerize all-trans-retinoic acid. 13-cis-Retinoic acid is the predominant cis isomer after incubation of intestinal mucosa homogenates with all-trans-retinoic acid. Moreover, the concentration of retinoic acid in serum is related to diet in that the level of total retinoic acid was 36% higher (n = 10) 2 h after a nonstandard breakfast than in fasting subjects. PMID- 2324642 TI - Metabolism of very low density lipoproteins in rats with isotretinoin (13-cis retinoic acid)-induced hyperlipidemia. AB - A significant rise in plasma triacylglycerols from the control level of 0.89 mmol/l to 1.88 mmol/l (P less than 0.001) was observed in male Sprague-Dawley rats treated for 11 days with isotretinoin (oral dosing; 10 mg/day). This rise was due to an increased level of plasma very low density lipoproteins (VLDL). When VLDL from untreated rats were labeled with 125I-labeled tyramine-cellobiose and injected intravenously into rats treated for 10 days with isotretinoin (n = 6) and in control rats (n = 6), it was found that the disappearance of radioactivity from the blood was dramatically retarded in the treated animals. The disappearance could be divided into two phases, a rapid (alpha) phase dominated the first 5 min and was followed by a slower (beta) phase. The half life of the beta-phase increased significantly from 53 +/- 7 min in the controls, to 120 +/- 62 min after isotretinoin. VLDL prepared from isotretinoin-treated animals (n = 6) had about the same half-life in control animals (62 +/- 8 min) as had ordinary VLDL. The elimination of tracer from the blood was mainly due to uptake by the liver. The amount of radioactivity in the liver after 30 min of circulation was significantly reduced from 34 +/- 7% of injected dose in controls to 24 +/- 5% in the isotretinoin group (P = 0.013). The uptake in other organs was less than 3% per organ and was essentially unaffected by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324643 TI - Metabolism of apoE-free high density lipoproteins in rat hepatoma cells: evidence for a retroendocytic pathway. AB - The cellular metabolism of apoE-free HDL (HDL) was studied in rat hepatoma cells (FU5AH). Cells incubated with HDL showed a dose-dependent decreased incorporation of [14C]acetate into cell sterol, indicating a net cholesterol delivery to the cells. HDL was localized both at the cell surface and inside the cell. This conclusion was drawn from both the association of 125I-labeled HDL with the cells under different experimental conditions and morphological evidence based on the association of colloidal gold-labeled HDL with the cells. Up to 63% of the 125I labeled HDL protein initially inside the cell was subsequently recovered in the media as trichloroacetic acid precipitable (TCA-ppt) protein after a 30-min, 37 degrees C chase with a 100-fold concentration of unlabeled HDL. About 27% of the TCA-ppt apoprotein originally inside the cell was recovered as TCA-soluble material. Thus, we conclude that of the HDL apoprotein taken up by the cells, the majority is resecreted by a retroendocytosis pathway. The quantity of HDL apoprotein reappearing in the media was stimulated by the presence of unlabeled HDL in the media, while the amount of TCA-soluble material produced was not. Retroendocytosis of HDL was inhibited at 0 degree C and by the presence of 10 mM NaCN, 20 mM 2-deoxy-D-glucose in the media. Thus, the pathway appears to be both temperature- and energy-sensitive. HDL resecreted by the cell were depleted of cholesteryl ester and showed an altered size distribution, indicative of lipoprotein catabolism and remodeling. This study provides evidence for the existence of an endocytosis-retroendocytosis pathway for HDL apoproteins in a rat hepatoma cell and for the possibility that the endocytosis-retroendocytosis pathway may be involved in lipid delivery to the cell. PMID- 2324644 TI - Differential regulation of low density lipoprotein suppression of HMG-CoA reductase activity in cultured cells by inhibitors of cholesterol biosynthesis. AB - Treatment of rat intestinal epithelial cells (IEC-6 cells) with lanosterol 14 alpha-demethylase inhibitors, ketoconazole and miconazole, had similar effects on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and cholesterol biosynthesis but the drugs differed in their ability to prevent the low density lipoprotein (LDL) suppression of reductase activity. Miconazole, at concentrations that inhibited the metabolism of lanosterol and epoxylanosterol to the same degree as ketoconazole, did not prevent low density lipoprotein action on reductase activity, whereas ketoconazole totally abolished the low density lipoprotein action on reductase activity. Both drugs caused: 1) a biphasic response in reductase activity such that at low concentrations (less than 2 microM) reductase activity was inhibited and at high concentrations (greater than 5 microM) the activity returned to control or higher than control levels; 2) an inhibition of metabolism of lanosterol to cholesterol, and 24(S), 25 epoxylanosterol to 24(S), 25-epoxycholesterol. Neither drug prevented suppression of reductase activity by 25-hydroxylanosterol, 25-hydroxycholesterol, or mevalonolactone added to the medium. Each drug increased the binding, uptake, and degradation of 125I-labeled LDL and inhibited the re-esterification of free cholesterol to cholesteryl oleate and cholesteryl palmitate. The release of free cholesterol from [3H]cholesteryl linoleate LDL could not account for the differential effect of ketoconazole and miconazole on the prevention of low density lipoprotein suppression of reductase activity. The differential effect of the drugs on low density lipoprotein suppression of reductase activity was not unique to IEC-6 cells, but was also observed in several cell lines of different tissue origin such as human skin fibroblast cells (GM-43), human hepatoblastoma cells (HepG2), and Chinese hamster ovary cells (wild type, K-1; 4 alpha-methyl sterol oxidase mutant, 215). These observations suggest that the suppressive action of low density lipoprotein on reductase activity 1) does not require the de novo synthesis of cholesterol, or 24(S), 25-epoxysterols; 2) is not mediated via the same mechanism as that of mevalonolactone; and 3) does not involve cholesteryl reesterification. Ketoconazole blocks a site in the process of LDL suppression of reductase activity that is not affected by miconazole. PMID- 2324645 TI - Altered bile acid metabolism in liver disease: concurrent occurrence of C-1 and C 6 hydroxylated bile acid metabolites and their preferential excretion into urine. AB - C-1 and C-6 hydroxylated bile acid metabolites in various biological specimens from subjects with liver disease (cholestasis, liver cirrhosis, chronic hepatitis, acute hepatitis) were determined by gas-liquid chromatography-mass spectrometry. Five C-1 hydroxylated bile acids and nine C-6 hydroxylated bile acids were identified in the urine studied; 1 beta,3 alpha,12 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy , 3 alpha,6 alpha,7 alpha-trihydroxy-, and 3 alpha,6 alpha,7 alpha,12 alpha tetrahydroxy-5 beta-cholanoic acids were found as the major components. Most of the 1 beta- and 6 alpha-hydroxylated bile acids were excreted into urine in the nonsulfate-nonglucuronide form. The amounts in the urine were greater than those found in the bile, portal and peripheral venous sera, and liver specimens. The biliary excretion and hepatic extraction of 1 beta-hydroxylated metabolites were more impaired and less efficient than for cholic acid. These findings suggested that hepatic 1 beta- or 6 alpha-hydroxylation of bile acids occurred concurrently in the patients with liver disease and that the resulting hydroxylated metabolites were efficiently excreted in the nonsulfate-nonglucuronide form into urine rather than into bile. PMID- 2324646 TI - Shape of the fluidity gradient in the plasma membrane of living HeLa cells. AB - The shape of the fluidity gradient of the outer hemi-leaflet of the plasma membrane of living HeLa cells was determined using a series of n-(9-anthroyloxy) fatty acid probes where n = 2, 3, 6, 7, 9, 10, 11, 12, and 16. Fluorescence uptake and steady-state anisotropy values were obtained with a flow cytometer capable of continuous recording over time of vertical and horizontal emission intensities, and of the output of these intensities as calculated anisotropy values. The fluorescence uptake of all of the membrane probes was rapid up to about 15 min. The magnitudes of the uptake of fluorescence were, for the n-(9 anthroyloxy) series, in the order 2 greater than 3 greater than 6 greater than 7 greater than 9 greater than 10 greater than 11 = 12 = 16. Anisotropy values were constant from 5 to 30 min after addition of the various probes, and the magnitudes were in the order 7 greater than 6 greater than 9 = 10 greater than 2 = 3 greater than 11 greater than 12 greater than 16, indicative of the shape of the fluidity gradient. No differences were noted between the values obtained with 12-(9-anthroyloxy) stearic acid and 12- (9-anthroyloxy) oleate. The kinetics of anisotropy exhibited by those probes with the anthroyloxy group in positions deeper than 9, where initially higher values declined until equilibrium was reached, were probably indicative of an energy barrier at the approximate depth sensed by 7 AS. PMID- 2324647 TI - Hepatic low density lipoprotein receptors, HMG-CoA reductase, and plasma lipids and apolipoproteins in high- and low-responding rhesus monkeys: effect of cholestyramine treatment. AB - Plasma lipids and apolipoproteins, and hepatic LDL receptor and HMG-CoA reductase activities in biopsy samples were measured in high- and low-responding rhesus monkeys maintained on a cholesterol-rich and regular diets. The effect of a 30 day cholestyramine treatment on the above parameters under both dietary conditions was also determined. On the cholesterol-rich diet the high-responders, when compared to the low-responders, had several-fold increased plasma cholesterol and apoB concentrations and significantly lower HDL apoA-I and cholesterol concentrations. Hepatic LDL receptor and HMG-CoA reductase activities were not detectable in the high-responders, while the low-responders expressed a reduced number of LDL receptors of normal affinity. Administration of cholestyramine resulted in a rapid induction of the hepatic LDL receptors in the high-responders and a small additional increase in the low-responders. Cholestyramine treatment also stimulated the expression of the hepatic HMG-CoA reductase in both groups of monkeys. These changes were accompanied by a dramatic drop in plasma cholesterol and apoB concentrations in the high-responders and, to a lesser extent, in the low-responders. Plasma HDL concentrations in the high responders rose to levels higher than those seen in the low-responders. The affinity and receptor number were similar in both groups of monkeys on the control diet, but the low-responders had significantly higher HMG-CoA reductase activities. Administration of cholestyramine during the control diet had a small but significant additional effect on the hepatic LDL receptors of the low responders but not of the high-responders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324648 TI - Physicochemical and biological properties of natural and synthetic C-22 and C-23 hydroxylated bile acids. AB - In order to define the effect of a side chain hydroxy group on bile acid (BA) physicochemical and biological properties, 23-hydroxylated bile acids were synthesized following a new efficient route involving the alpha-oxygenation of silylalkenes. 22-Hydroxylated bile acids were also studied. The synthesized bile acids included R and S epimers of 3 alpha,7 alpha,23-trihydroxy-5 beta-cholan-24 oic acid (23R epimer: phocaecholic acid), 3 alpha,12 alpha,23-trihydroxy-5 beta cholan-24-oic (23R epimer: bitocholic acid), and 3 alpha,7 beta,23-trihydroxy-5 beta-cholan-24-oic acid. A 3 alpha,7 alpha,22-trihydroxy-5 beta-cholan-24-oic acid (haemulcholic acid) was also studied. The presence of a hydroxy group on the side chain slightly modified the physicochemical behavior in aqueous solution with respect to common BA: the critical micellar concentration (CMC) and the hydrophilicity were similar to naturally occurring trihydroxy BA such as cholic acid. The pKa value was lowered by 1.5 units with respect to common BA, being 3.8 for all the C-23 hydroxy BA. C-22 had a higher pKa (4.2) as a result of the increased distance of the hydroxy group from the carboxy group. When the C-23 hydroxylated BA were intravenously administered to bile fistula rats, they were efficiently recovered in bile (more than 80% unmodified) while the corresponding analogs, lacking the 23- hydroxy group, were almost completely glycine- or taurine-conjugated. On the other hand, the C-22 hydroxylated BA were extensively conjugated with taurine and less than 40% of the administered dose was secreted without being conjugated. In the presence of intestinal bacteria, they were mostly metabolized to the corresponding 7-dehydroxylated compound similar to common BA with the exception of bitocholic acid which was relatively stable. The presence of a hydroxy group at the C-23 position increased the acidity of the BA and this accounted for poor absorption within the biliary tree and efficient biliary secretion without the need for conjugation. 3 alpha,7 beta-23 R/S trihydroxy-5 beta-cholan-24-oic acids could improve the efficiency of ursodeoxycholic acid (UDCA) for gallstone dissolution or cholestatic syndrome therapy, as it is relatively hydrophilic and efficiently secreted into bile without altering the glycine and taurine hepatic pool. PMID- 2324649 TI - Identification of metabolites from peroxisomal beta-oxidation of prostaglandins. AB - We have recently shown that isolated rat liver peroxisomes can chain-shorten prostaglandin F2 alpha and prostaglandin E2 to tetranor-metabolites. In the present report dinor-metabolites of these two prostaglandins were also identified, suggesting that the peroxisomal chain-shortening reaction of prostaglandins is a beta-oxidation reaction. Furthermore, an intermediate containing an extra double bond was isolated from incubates of prostaglandin F2 alpha with peroxisomes. This intermediate was tentatively assigned the structure 2,3-dehydroprostaglandin F2 alpha. Prostaglandin E1 and a major circulating prostaglandin F2 alpha metabolite were also metabolized to chain-shortened products by peroxisomes. The accumulation of the 2,3-dehydro-metabolite and the dinor-metabolites suggest that the peroxisomal beta-oxidation sequence is not tightly coupled, in contrast to mitochondrial fatty acid oxidation. PMID- 2324650 TI - Synthesis and applicability of photolabile 7,7-azo analogues of natural bile salt precursors. AB - In an approach to the identification of proteins involved in the side chain degradation of bile salt biosynthesis, the photolabile 7,7-azo derivatives of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan 26-oate were synthesized. All 7,7-azo derivatives were metabolized by intact rat liver and freshly isolated rat hepatocytes in the same manner as the nonphotolabile physiological intermediates, resulting in the formation of the 7,7 azo analogues of cholyltaurine and cholylglycine. Photolysis of all three photolabile derivatives, using a light source with a maximum emission at 350 nm, occurred with a half-life of 2.1 min; their efficacy for photoaffinity labeling was demonstrated by incorporation into rat serum albumin. PMID- 2324651 TI - Effects of phorbol 12-myristate 13-acetate on triglyceride and cholesteryl ester synthesis in cultured coronary smooth muscle cells and macrophages. AB - In cultured pig coronary smooth muscle cells phorbol 12-myristate 13-acetate (PMA) stimulated the conversion of [4-14C]cholesterol into cholesteryl esters and the incorporation of [2-3H]glycerol into triglycerides 6.4- and 4.5-fold, respectively. The maximal effects occurred after 3 h of treatment and there was a return to basal values after 72 h. In the presence of 400 microM oleic acid, PMA stimulated the conversion of [4-14C]cholesterol into cholesteryl esters and that of [2-3H]glycerol into triglycerides 5.3- and 2.3-fold, respectively. The stimulatory effects were more sustained (still significant after 72 h) and their maxima were delayed (peaks after 24 h). PMA was also found to increase 2-fold the amount of triglyceride that accumulated in the cells in the presence of oleic acid after 24 h. In macrophages IC-21, the effects of PMA were observed only in the presence of oleic acid. They consisted of a 1.9-fold stimulation in the conversion of [4-14C]cholesterol into cholesteryl esters after 72 h and of a 1.7 fold stimulation in the incorporation of [2-3H]glycerol into triglycerides after 24 h. PMA also increased the amount of triglyceride that accumulated in the cells 1.9-fold after 72 h. It is concluded that PMA, and possibly growth factors, may promote lipid storage in smooth muscle cells and that fatty acids favor long lasting effects of PMA in smooth muscle cells and are necessary for any effect of PMA in macrophages. PMID- 2324652 TI - Rapid isolation of vesicular and micellar carriers of biliary lipids by ultracentrifugation. AB - A simple, rapid, and new method has been developed to isolate and to quantitate the vesicular carrier of biliary lipids by isopycnic ultracentrifugation. The method combines the use of Metrizamide, as an inert centrifugation media to change the density of bile for isopycnic separation of vesicles, and a vertical rotor, to decrease both the time of centrifugation and the pressure of the hydrostatic column in the ultracentrifuge tube. Vesicles harvested from bile Metrizamide density gradients were identified by negative staining electron microscopy. The buoyant densitites of biliary vesicles varied between 1.010 and 1.030 g/ml. The diameter of vesicles in fractions with d less than 1.020 g/ml was 82 +/- 10 nm and in fraction with d approximately 1.030 g/ml was 57 +/- 8 nm. Gel filtration chromatography with Ultrogel AcA 34 was used to validate the quantitive isolation of vesicles by the ultracentrifugal method. In experiments with bile-Metrizamide continuous preformed density gradients, greater than 93% of vesicular cholesterol was found in fractions with d less than 1.030 g/ml after 285 min of centrifugation at 50,000 rpm in a VTi vertical rotor (Beckman Instruments, Inc.). When 16% Metrizamide was dissolved in bile and centrifuged for 120 min, greater than 96% of total vesicular cholesterol was found in the top 0.4 ml of the 5-ml centrifuge tube, as assessed by gel filtration chromatography. This fraction contained less than 8% of cholesterol carried in micelles, as assessed by gel filtration chromatography. The variation coefficient of this short ultracentrifugal method to isolate biliary vesicles was 4.6%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324653 TI - Rapid labeling of lipoproteins in plasma with radioactive cholesterol. Application for measurement of plasma cholesterol esterification. AB - In order to efficiently and rapidly label lipoproteins in plasma with [3H]cholesterol, micelles consisting of lysophosphatidylcholine (lysoPC) and [3H]cholesterol (molar ratio, 50:1) were prepared. When trace amounts of these micelles were injected into plasma, [3H]cholesterol rapidly equilibrated among the plasma lipoproteins, as compared to [3H]cholesterol from an albumin stabilized emulsion. The distributions of both [3H]cholesterol and unlabeled free cholesterol in plasma lipoproteins were similar in labeled plasma samples. This method of labeling can be used for the measurement of cholesterol esterification, or lecithin:cholesterol acyltransferase activity, in small amounts (20-40 microliters) of plasma samples. PMID- 2324654 TI - A simplified method for synthesizing juvenile hormone-protein conjugates. AB - A convenient and simple method is presented for the synthesis of juvenile hormone thyroglobulin conjugates. Methods previously described for this hapten linkage have used a two-step process in which a reactive intermediate was isolated and then used for conjugation. With the approach described here, an efficient, single step conjugation reaction is effected between the carboxyl moiety of juvenile hormone III and the carrier protein, bovine thyroglobulin. Isolation of the reactive intermediate is eliminated. Isotopic dilution indicates that between 100 and 115 moles of hapten are conjugated per mole of carrier protein. PMID- 2324655 TI - Pressure pain threshold evaluation of the effect of spinal manipulation in the treatment of chronic neck pain: a pilot study. AB - Nine subjects with chronic mechanical neck pain syndromes were evaluated for pressure pain threshold (PPT) over standardized tender points in the paraspinal area surrounding a manipulable spinal lesion. The subjects were then allocated randomly to an intervention consisting of either an oscillatory mobilization of the cervical spine (n = 4), which was designated as the control procedure, or a rotational manipulation of the cervical spine (n = 5). An assessor-blinded re evaluation of the pressure pain threshold levels was conducted after 5 min. In the group receiving a manipulation the mean increases in pressure pain threshold ranged from 40-56% with an average of 45%. In the control group no change in any of the pressure pain thresholds was found. These results were analyzed using ANOVA and were found to be statistically significant (p less than 0.0001). This study confirms that manipulation can increase local paraspinal pain threshold levels. The use of the pressure pain threshold meter allows for the determination of such a beneficial effect in the deeper tissues. PMID- 2324658 TI - Publishing research. PMID- 2324656 TI - Rib fracture due to bench pressing. AB - Rib fractures are commonly associated with blunt trauma, but there are instances where this is not the case. In this case a patient fractured the second rib during a "bench press" weight lifting maneuver. The possible etiology is proposed, and the incidence, causes, diagnosis, complications, and treatment of rib fractures are discussed. PMID- 2324657 TI - Anticoagulant therapy and subdural hematoma formation. AB - Subdural hematoma formation should be considered as a diagnosis in the patient who complains of headache and is on long-term anticoagulant therapy. Three such cases are described and the proper medical management is discussed. PMID- 2324659 TI - A critical look at the subluxation hypothesis. PMID- 2324660 TI - Chiropractic in the yellow pages: a content analysis study. PMID- 2324661 TI - Beyond the theosophy of chiropractic. PMID- 2324662 TI - The validation of the diagnosis "joint dysfunction" in the synovial joints of the cervical spine. AB - One hundred patients suffering from cervical spine involvement were examined using procedures developed by the author over a period of many years. The cases were analyzed on the basis of incidence of sex and age, duration of symptoms, role of injury, analysis of radiographic examination and assessment of manipulative treatment. Of the 100 patients, 83 underwent manipulative therapy. Thirty percent of those treated reported cessation of symptoms, and another 34% felt they had markedly improved. It is felt that such information helps to validate the presence of joint dysfunction as a manipulable condition. PMID- 2324663 TI - Choice with uncertain outcomes: conditioned reinforcement effects. AB - Pigeons responded on concurrent chains with equal initial- and terminal-link durations. In all conditions, the terminal links of one chain ended reliably in reinforcement; the terminal links on the alternative chain ended in either food or blackout. In Experiment 1, the terminal-link stimuli were correlated with (signaled) the outcome, and the durations of the initial and terminal links were varied across conditions. Preference did not vary systematically across conditions. In Experiment 2, terminal-link durations were varied under different stimulus conditions. The initial links were variable-interval 80-s schedules. Preference for the reliable alternative was generally higher in unsignaled than in signaled conditions. Preference increased with terminal-link durations only in the unsignaled conditions. There were no consistent differences between conditions with and without a common signal for reinforcement on the two chains. In the first series of conditions in Experiment 3, a single response was required in the initial links, and the stimulus conditions during 50-s terminal links were varied. Preference for the reliable outcome approached 1.0 in unsignaled conditions and was considerably lower (below .50 for 3 of 5 subjects) in signaled conditions. In a final series of signaled conditions with relatively long terminal links, preference varied with duration of the initial links. The results extend previous findings and are discussed in terms of the delay reduction signaled by terminal-link stimuli. PMID- 2324664 TI - Suboptimal choice in a percentage-reinforcement procedure: effects of signal condition and terminal-link length. AB - Pigeons' choice between reliable (100%) and unreliable (50%) reinforcement was studied using a concurrent-chains procedure. Initial links were fixed-ratio 1 schedules, and terminal links were equal fixed-time schedules. The duration of the terminal links was varied across conditions. The terminal link on the reliable side always ended in food; the terminal link on the unreliable side ended with food 50% of the time and otherwise with blackout. Different stimuli present during the 50% terminal links signaled food or blackout outcomes under signaled conditions but were uncorrelated with outcomes under unsignaled conditions. In signaled conditions, most pigeons displayed a nearly exclusive preference for the 100% alternative when terminal links were short (5 or 10 s), but with terminal links of 30 s or longer, preference for the 100% alternative was sharply reduced (often to below .5). In unsignaled conditions, most pigeons showed extreme preference for the 100% alternative with either short (5 s) or longer (30 s) terminal links. Thus, pigeons' choice between reliable and unreliable reinforcement is influenced by both the signal conditions on the unreliable alternative and the duration of the terminal-link delay. With a long delay and signaled outcomes, many pigeons display a suboptimal tendency to choose the unreliable side. PMID- 2324665 TI - Operant hoarding: a new paradigm for the study of self-control. AB - In the first of four experiments, rats were exposed to a modified multiple continuous reinforcement-extinction schedule during 15-min daily sessions. In one condition (saves condition) with the cuelight on, a single lever press produced a food pellet, briefly extinguished the cuelight, and started a clock. Saves (additional lever presses with interresponse times less than 1 s) produced an additional food pellet, briefly extinguished the cuelight, and restarted the interresponse time clock. The cuelight was extinguished 1 s after the last lever press and remained off during a 10-s period of extinction, during which no food pellets were delivered. In the other condition (savings account condition), the contingencies were the same except that the cuelight was extinguished and was not reilluminated after the initial lever press, and the delivery of all food pellets in the reinforcement component was delayed until the onset of extinction. In both conditions, rats made saves, but mean saves (total saves divided by the number of reinforcement components) were slightly reduced in the savings account condition. In Experiment 2, using six equally spaced 15-min sessions per day on alternate days, saves were either followed immediately with food and brief cuelight offset (saves condition) or were not reinforced at all. Mean saves were much greater when saves were reinforced. In Experiment 3, during 5-min daily sessions, saves earned a single pellet (savings account condition) or a number of pellets equal to the ordinal number of the lever press (interest condition). Rats made fewer mean saves, with little change in the food rate, when saves earned interest. In Experiment 4, the rats earned all their food in the operant situation during 24 daily 5-min sessions, these separated by 55-min intersession intervals during which no food was available; otherwise, the conditions were the same as in Experiment 3. In Experiment 4, the shift to interest for saves led to an increase in mean daily mean saves (total daily mean saves divided by the number of daily sessions) as well as to an increase in the number of food pellets delivered in each session. The results are discussed in terms of self-control and behavioral economics. PMID- 2324666 TI - Quinine pellets as an inferior good and a Giffen good in rats. AB - In Experiment 1, 4 rats earned their daily food ration by choosing between two levers. One lever delivered two regular and one quinine-adulterated food pellets, and the other delivered two regular and four quinine pellets. A 20-s intertrial interval separated successive choices. Sessions began with 10 forced trials during which only one lever, selected with p = .5 and cued by a light above it, could deliver its reinforcer. Forced trials were followed by 30 or 150 trials, depending on the condition, during which choices to either lever could be reinforced. Over this range, absolute choice of the four-quinine, two-regular pellet lever was inversely related to the number of free-choice trials, establishing this reinforcer as an inferior good. In Condition 1 of Experiment 2, the prior design was altered in two ways: (a) one lever delivered four quinine pellets, and the other lever delivered one standard pellet; and (b) sessions ended after 140 free-choice trials. When the number of free-choice trials was reduced to 100 (Condition 2), all 3 rats increased their preference for quinine pellets, confirming their status as an inferior good. In the next several conditions, the number of quinine pellets provided for selecting its associated lever was varied between three and four. Preference for the quinine-pellet alternative was inversely related to the number of pellets it provided, a result defining it as a Giffen good. These findings are not accommodated readily by extant choice models and complicate the search for a unitary model of choice. PMID- 2324667 TI - A functional analysis of another individual's behavior as discriminative stimulus for a monkey. AB - Key presses of 1 monkey (called the performer) became the basis upon which a 2nd monkey (called the judge) solved conditional-discrimination tasks. First, the performer was trained to press one of two colored choice keys (red or green) depending on the location of a white light in her chamber. The performer's key pressing behavior was brought under the control of the experimenter by this procedure. Subsequently, the judge was trained to discriminate the performer's key-pressing behavior. In Experiment 1, the judge had to press Key 1 when the performer pressed the red choice key and Key 2 when the performer pressed the green choice key. In Experiment 2, a sample key was introduced. The judge had to press Key 1 when the performer pressed the same colored choice key as the sample; the judge had to press Key 2 when the performer pressed the different colored choice key. In both experiments, the judge was required to attend to the behavior of the performer. It was shown that the performer's behavior served as a discriminative stimulus for the judge's responses in a conditional-discrimination task. PMID- 2324668 TI - Human aggressive responses maintained by avoidance or escape from point loss. AB - During 50-min sessions, 6 male human subjects could press either Button A or Button B available as nonreversible options. Button A presses were nonaggressive responses and earned points according to a fixed-ratio 100 schedule. Prior to the experiment subjects were instructed that every 10 (fixed-ratio 10) Button B presses (aggressive responses) subtracted a point from a fictitious 2nd subject. A random-time schedule of point loss was used to engender aggressive responding. The instructions attributed these point losses to the Button B presses of the subject's fictitious partner. Aggressive responding either escaped or avoided point loss by initiating an interval free of point loss. The duration of the interval was varied systematically across sessions. Avoidance contingencies maintained a high rate of aggressive responding over 30 sessions in the absence of point loss. Escape contingencies also maintained aggressive responding across sessions, with rates of aggressive responding corresponding to rates of point loss. PMID- 2324669 TI - Production of thiosulphate during sulphide oxidation by mitochondria of the symbiont-containing bivalve Solemya reidi. AB - Isolated mitochondria of the bivalve Solemya reidi Bernard oxidize sulphide and couple this oxidation to ADP phosphorylation. The products of mitochondrial sulphide oxidation were analyzed by HPLC using monobromobimane derivatization. Concurrent measurements of respiration were made using sulphide-insensitive oxygen electrodes. S. reidi mitochondria oxidized sulphide exclusively to thiosulphate. The reaction occurred in two steps. One sulphide molecule was first oxidized to sulphite. A second molecule of sulphide was then added oxidatively to form the free product thiosulphate. This oxidation was obligately linked to mitochondrial electron transport and could be inhibited by the cytochrome c oxidase inhibitor hydrogen cyanide, or by low oxygen concentration. The site II inhibitor antimycin A did not inhibit thiosulphate production, indicating that sulphide oxidation is linked through only one ATP coupling site (site III). A calculation of the respiratory potential for ATP synthesis by fully intact mitochondria indicated that 2.0-3.25 ATP per sulphide may be synthesized using the proton potential generated by sulphide oxidation. This estimate far exceeds the published phosphorylation ratios for S. reidi (0.5-1.2 ATP per sulphide). This difference may be accounted for by partial uncoupling of phosphorylation from sulphide-based respiration. This hypothesis is supported by the observation that the respiratory control ratio of mitochondria respiring on sulphide is 41% lower than that of mitochondria respiring on succinate. The respiratory control ratio is an index of the tightness of coupling of respiration to ADP phosphorylation. When the adenylate pool of a eukaryotic cell is mostly phosphorylated, respiration is very slow, owing to the maintenance of a high mitochondrial membrane potential. Uncoupling of oxidative phosphorylation from respiration would be an adaptive advantage to the animal in that it allows for continuous, rapid removal of the toxic molecule hydrogen sulphide. PMID- 2324670 TI - Ultrasound-induced yaw movements in the flying Australian field cricket (Teleogryllus oceanicus). AB - An ultrasonic stimulus induced negative phonotactic steering in the yaw axis of tethered, flying Australian field crickets. The forewings, hindwings and twisting of the thorax generated the forces which induced the yaw turn. However, abdominal ruddering did not contribute to yaw turns. Each aspect of the yaw steering response depended upon the stimulus intensity. At higher ultrasonic intensities, the magnitude and average angular velocity increased while the latency of the yaw turn decreased. Each of these factors varied in a graded manner, revealing that this behavior is more complex than a simple reflex. PMID- 2324671 TI - What causes edge fixation in walking flies? AB - The orientation of freely walking flies (female Lucilia cuprina) to lines and stripes in a circular arena is described. The following observations were made. 1. The flies walked straight towards a dark line using the frontal eye region, but a pale line on a dark background was only weakly attractive. 2. In bright conditions flies walked in a curved line towards a black-white edge, the path being convex towards the dark side of the border. The curves indicated that the flies were heading for a point about 5-10 degrees to the dark side of the edge. 3. In dim conditions the edge of a dark region was not especially attractive and flies headed towards any point in the dark area. These observations can be accounted for by assuming that the fly walks towards the darkest region in its visual field (scototaxis). In bright conditions the edges of a dark region become more attractive than its centre. This change could be explained if lateral inhibition creates a 'Mach-band' effect, making the edges appear darker than the centre. Thus, fixation behaviour in walking Lucilia females seems to be a simple taxis. PMID- 2324672 TI - Energetics of ascent: insects on inclines. AB - Small animals use more metabolic energy per unit mass than large animals to run on a level surface. If the cost to lift one gram of mass one vertical meter is constant, small animals should require proportionally smaller increases in metabolic cost to run uphill. To test this hypothesis on very small animals possessing an exceptional capacity for ascending steep gradients, we measured the metabolic cost of locomotion in the cockroach, Periplaneta americana, running at angles of 0, 45 and 90 degrees to the horizontal. Resting oxygen consumption (VO2rest) was not affected by incline angle. Steady-state oxygen consumption (VO2ss) increased linearly with speed at all angles of ascent. The minimum cost of locomotion (the slope of the VO2ss versus speed function) increased with increasing angle of ascent. The minimum cost of locomotion on 45 and 90 degrees inclines was two and three times greater, respectively, than the cost during horizontal running. The cockroach's metabolic cost of ascent greatly exceeds that predicted from the hypothesis of a constant efficiency for vertical work. Variations in stride frequency and contact time cannot account for the high metabolic cost, because they were independent of incline angle. An increase in the metabolic cost or amount of force production may best explain the increase in metabolic cost. Small animals, such as P. americana, can easily scale vertical surfaces, but the energetic cost is considerable. PMID- 2324673 TI - Primary culture of crustacean stomatogastric ganglion neurones in a defined medium. PMID- 2324675 TI - Sarcoidosis and pregnancy: a review with results of a retrospective survey. PMID- 2324674 TI - Insulin resistance--a major hazard for cardiovascular disease? PMID- 2324676 TI - Ratio of cuff width/arm circumference as a determinant of arterial blood pressure measurements in adults. AB - Recommendations state that the optimum ratio of blood pressure cuff width/arm circumference (CW/AC) is about 0.4. In this study of middle-aged men (n = 940) and women (n = 1484), we analysed the effect of CW/AC on blood pressure measurement variability and its interaction with age, body mass index (BMI), pulse rate and room temperature. In univariate polynomial regression, the variability (R2) in blood pressure that was explained by CW/AC was greater for women (systolic 6.3% and diastolic 5.7%) than for men (2.0% and 0.5%). In multivariate analysis the maximum variability explained independently by CW/AC was 2.7% for male and 6.7% for female systolic blood pressure, and 1.1% and 6.0% for male and female diastolic blood pressure, respectively. For systolic blood pressure this represented 10.4% of the explained variability in men and 9.3% of that in women. CW/AC is an important independent contributor to inter-individual variation in blood pressure measurement. It should therefore be taken into consideration in epidemiological studies and when medical care is being planned. PMID- 2324677 TI - Epidemiology of biopsy-proven giant cell arteritis (GCA). AB - During a 10-year period from 1st January 1977 to 31st December 1986, a temporal artery biopsy was performed in 2307 patients in the city of Goteborg. The biopsy revealed giant cell arteritis (GCA) in 284 (12.5%) of patients. The average annual incidence of biopsy-proven GCA was 6.7 per 100,000 inhabitants. For women and men it was 9.9 and 3.5 per 100,000 inhabitants, respectively. In individuals aged 50 years or older, the average incidence was 18.3 per 100,000 inhabitants, with values of 25 and 9.4 for women and men, respectively. The annual incidence rate increased significantly (P less than 0.01) for women, but not for men; this result was not explained by demographic changes in the population. PMID- 2324678 TI - Temporal arteritis: the silent presentation and delay in diagnosis. AB - To determine the frequency of the so-called silent or occult presentation of temporal arteritis (presentation with mere constitutional symptoms) and the resulting delay in diagnosis in this particular group, the medical records of all patients (n = 82) with temporal arteritis or polymyalgia rheumatica, presenting between 1982 and 1988 at the Department of General Internal Medicine of the University Hospital, were retrospectively analysed. Only biopsy-proven cases (n = 34) were studied further. Of the 34 patients with temporal arteritis, 13 (38%) presented with the silent or occult form. In this group the mean delay in diagnosis was 21.5 d (range 2-105) in contrast to a delay of 8.5 d (range 1-40) in the other group (P less than 0.05). Increased awareness of this presentation should lead to earlier diagnosis and treatment of this potentially life threatening disease, resulting in a shorter hospital stay and fewer technical investigations, with a considerable financial saving. PMID- 2324679 TI - Prevalence of obesity in Sweden: cross-sectional study of a representative adult population. AB - In order to facilitate research on body weight related diseases, and to plan suitable prevention and intervention programmes, data concerning the prevalence of overweight and obesity are required on a nationwide scale. In this study, data for weight and height from a representative sample (n = 14,549) of adult Swedes (16-84 years of age) were analysed. Data were obtained from the Study on Living Conditions conducted by Statistics Sweden, and body mass indices (BMI, kg m-2) were calculated from these interviews. They were then calibrated, since we had previously found that reported anthropometric measurements must be corrected so as to conform to recorded height and weight values, and we have developed equations accordingly. The overall mean BMI (+/- SE) was 24.02 +/- 0.99 kg m-2 for women and 24.56 +/- 0.88 kg m-2 for men. However, with regard to age, striking differences between the sexes were observed using this cross-sectional approach. Whereas in men there was a moderate increase in BMI with age, there was a sharp increase in women from 45-54 years onwards. If obesity is defined according to WHO recommendations (BMI for men greater than 30.0 kg m-2, and for women greater than 28.6 kg m-2), then 34.5% of all men in our sample were found to be overweight and 6.6% were found to be obese. The corresponding figures for women are 31.2% and 13.1%. Our data suggest that, on a nation-wide scale, overweight and obesity are common in men and women, but in women there is a marked increase from the menopause onward, for reasons that have yet to be clarified. PMID- 2324680 TI - Novel gene mutations at the low density lipoprotein receptor locus: FH-Kanazawa and FH-Okayama. AB - Gene mutations at the low density lipoprotein (LDL) receptor locus were screened in 210 alleles of Japanese patients with familial hypercholesterolaemia (FH). In the present study, two types of novel mutation were identified by genomic Southern blotting using human LDL receptor cDNA probes. An approximately 12 kb deletion including exons 2 and 3 (and possibly 4) was identified in a patient (M.I.). The patient with this mutant gene will be referred to as 'FH-Kanazawa'. Two patients born in Okayama Prefecture in Japan had another unique 13 kb partial deletion, from exons 7 to 14, in their LDL receptor genes (FH-Okayama). This mutant allele is the first reported case in which the central portion of the LDL receptor gene, the epidermal growth factor (EGF) precursor homology region, is eliminated. PMID- 2324682 TI - Temporal arteritis with normal erythrocyte sedimentation rate. PMID- 2324681 TI - Correlation of serum cytokine levels with haematological abnormalities in human immunodeficiency virus infection. AB - Mononuclear phagocyte-derived cytokines are important regulators of haemopoiesis in inflammatory conditions. By means of radioimmunoassay we measured the levels of two cytokines, tumour necrosis factor-alpha and interleukin 1 beta in sera from subjects infected with human immunodeficiency virus, and related the levels to the presence and severity of haematological abnormalities. The levels of tumour necrosis factor-alpha were significantly higher in patients with anaemia (142 +/- 17 (SE) pg ml-1), lymphopenia (107 +/- 20 pg ml-1) or both (137 +/- 21 pg ml-1) than in individuals without anaemia (18 +/- 5 pg ml-1; P less than 0.001), without lymphopenia (16 +/- 7 pg ml-1; P less than 0.001) or without either disorder (19 +/- 7 pg ml-1; P less than 0.001). A strong negative correlation was found between tumour necrosis factor-alpha and haemoglobin values (r = -0.83, P less than 0.001) and absolute lymphocyte count (r = -0.66, P less than 0.001) in human immunodeficiency virus infection. The changes in the levels of serum interleukin 1 beta were less pronounced but followed the same general trend as the changes in tumour necrosis factor-alpha. The results show that the production of mononuclear phagocyte-derived cytokines is enhanced in acquired immunodeficiency syndrome, and that the levels of these factors are correlated with the presence of certain haematological abnormalities. PMID- 2324683 TI - Direct diabetogenic effect of diltiazem? AB - In the reported case history, a normotensive and non-diabetic patient with ischaemic heart disease was treated twice with diltiazem. On both occasions diabetes mellitus developed within a few days; at first this was fully reversible, but on the last occasion it was irreversible. PMID- 2324684 TI - Lipid peroxides, glutathione peroxidase, high density lipoprotein subfractions and apolipoproteins in young adults. AB - Lipid peroxides have been implicated in the initiation of atherogenesis. In this study of 23 young healthy subjects, high levels of serum lipid peroxides were associated with low serum HDL2 cholesterol concentrations and low HDL2/HDL3 cholesterol and apolipoprotein A-I/A-II ratios. Low levels of LDL cholesterol and apolipoprotein B, and low apolipoprotein B/A-I ratios were typical of subjects with high serum glutathione peroxidase activities. Serum lipid peroxide levels varied widely in subjects without abnormal cholesterol, HDL cholesterol or LDL cholesterol concentrations. This variation may play a role in the frequent occurrence of coronary artery disease in normolipidaemic individuals. PMID- 2324685 TI - Infection of monocytes by human immunodeficiency virus type 1 blocked by inhibitors of CD4-gp120 binding, even in the presence of enhancing antibodies. AB - Infection of monocyte/macrophages (M/M) by a variety of viruses (including HIV-1) has been shown to be enhanced in the presence of low concentrations of antiviral antibodies. This process has been hypothesized as occurring through binding of the virus-antibody complex to Fc or complement receptors followed by endocytosis. In the current study, we explored whether such a mechanism might provide a CD4 independent route of infection by HIV-1 for any of several populations of M/M. In the absence of anti-HIV antibodies, replication of HIV-1 in M/M was blocked by viral binding inhibitors such as soluble CD4 or OKT4A mAb. Furthermore, while infection of the M/M populations by a low multiplicity of infection of HIV-1 was found to be somewhat enhanced by the presence of very low concentrations of anti HIV antibodies, this process was also consistently inhibited by recombinant soluble CD4 and by OKT4A antibody. These results suggest that under the variety of conditions studied, CD4 binding was an essential step in the infection of M/M by HIV. Moreover, they are consistent with the notion that "enhancing" antibodies may serve to concentrate HIV onto CD4 receptors or, alternately, may act at other steps in the process of viral entry and replication. PMID- 2324686 TI - Murine interleukin 7 (IL-7) receptor. Characterization on an IL-7-dependent cell line. AB - A murine cell line (IxN/2b) absolutely dependent upon exogenous IL-7 for continued growth has been obtained that expresses lymphoid precursor and class I MHC antigens and also contains a rearranged mu heavy chain. This cell line has been used to define the binding and structural characteristics of the murine IL-7 receptor using 125I-labeled recombinant murine IL-7. 125I-IL-7 binding to IxN/2b cell was rapid and saturable at both 4 degrees and 37 degrees C. Equilibrium binding studies produced curvilinear Scatchard plots at both temperatures with high and low affinity Ka values of approximately 1 x 10(10) M-1 and 4 x 10(8) M 1, respectively, and a total of 2,000-2,500 IL-7 binding sites expressed per cell. Experiments measuring inhibition of binding of 125I-IL-7 by unlabeled IL-7 also produced data consistent with the existence of two classes of IL-7 receptors. Evidence concerning the possible molecular nature of two classes of IL 7 receptors was provided by dissociation kinetics and affinity crosslinking experiments. The dissociation rate of 125I-IL-7 was markedly increased when measured in the presence of unlabeled IL-7 at both 37 degrees and 4 degrees C, which is diagnostic of a receptor population displaying negative cooperativity. Crosslinking studies showed that under both reducing and nonreducing conditions, the major crosslinked species observed corresponded to a receptor size of 75-79 kD while a less intense higher molecular mass crosslinked species was also seen which corresponded to a receptor size approximately twice as large (159-162 kD). Both types of experiments suggest that the IL-7 receptor may form noncovalently associated dimers in the membrane. The IL-7 receptor was expressed on pre-B cells, but not detected on several murine B cell lines or primary mature B cells. It was also expressed on murine thymocytes, some T lineage cell lines, and on bone marrow-derived macrophage. All cells binding 125I-IL-7 exhibited curvilinear Scatchard plots. No cytokines or growth factors tested were able to inhibit binding of 125I-IL-7 to its receptor. These results define the initial binding and structural characteristics, and the cellular distribution, of the murine IL-7 receptor. PMID- 2324687 TI - Animals bearing malignant grafts reject normal grafts that express through gene transfer the same antigen. AB - Breaking the state of immunological unresponsiveness of tumor-bearing individuals to cancer is a prerequisite for active or passive tumor-specific immunotherapy. To study this problem the immunogenic MHC class I antigen, K216 was transfected into a progressor tumor. The transfected tumors were regularly rejected by normal mice but grew progressively in mice bearing nontransfected tumors. In addition, transgenic mice were derived to obtain normal cells and tissues expressing the same K216 gene product. Normal mice rejected K216-positive normal or malignant tissue grafts and generated K216-specific CTL in vitro and in vivo in response to these challenges. In contrast, mice bearing nontransfected tumors, though rejecting K216-positive nonmalignant tissue grafts, did not reject K216-positive tumors nor generate K216-specific CTL in response to K216-positive tumor cells. Mice bearing K216-positive tumors also rejected the nonmalignant K216-positive tissue grafts, but this in vivo response failed to lead to rejection of the simultaneously present tumor graft expressing the same antigen; in fact, immunity had no measurable effect whatsoever on tumor size or incidence and caused no selection for antigen loss variants. Taken together, the present findings suggest that transfer of expression of a target antigen into nonmalignant cells provides a way for obtaining effective stimulation of antigen-specific CTL in tumor bearing mice, but that additional manipulations will be required to cause immunological rejection of established tumors. PMID- 2324688 TI - The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product. AB - The gp75 antigen is an abundant intracellular glycoprotein expressed in melanosomes of human pigmented melanocytes and melanomas. IgG antibodies in sera of a patient with metastatic melanoma have been shown to immunoprecipitate gp75, suggesting that immunological tolerance against gp75 can be broken. The mouse mAb TA99, which specifically recognizes gp75, was used to isolate and purify the antigen. Amino acid sequences of three internal peptides were determined from the purified gp75 polypeptide. cDNA clones were isolated by screening with oligonucleotides based on these peptide sequences. The gp75 peptides and cDNA had approximately 90% identity with, respectively, the derived amino acid and nucleotide sequences of a mouse gene that maps to the b (brown) locus. The brown locus determines coat color in the mouse, suggesting that gp75 regulates or influences the type of melanin synthesized. PMID- 2324689 TI - Prenatal screening for hepatitis B. PMID- 2324691 TI - Procedures in family practice. PMID- 2324690 TI - Obstetric training. PMID- 2324692 TI - Questioning thoughts from across the Atlantic. PMID- 2324693 TI - Sex and race are risk factors for colorectal cancer within reach of the sigmoidoscope. AB - There is controversy about the efficacy and feasibility of flexible fiberoptic sigmoidoscopy (FFS) as a screening test for colorectal cancer in asymptomatic adults aged 50 years and over. Some authorities recommend periodic FFS screening for all such adults, whereas other authorities do not recommend screening FFS at all. There is evidence that some physicians have adopted a policy of "selective screening" by emphasizing screening FFS for adults with ancillary risk factors such as a personal history of colon polyps or previous colorectal cancer, or a family history of colon, female genital, or breast cancer. Results of this study of the subsite distribution of colorectal cancer show that both male sex and Oriental race are risk factors for colorectal cancer within reach of FFS, and that the risk of being male and Oriental (relative risk [RR] = 1.9) is of the same magnitude as that for other ancillary risk factors known for the general population (excluding specific rare disorders). Knowledge that sex and race are risk factors for colorectal cancer detectable by screening FFS may be important to those physicians who choose the selective screening approach. Further research is necessary to determine whether selective screening for colorectal cancer is efficacious, or whether the race and sex differences noted in this study are important in the etiology of colorectal cancer. PMID- 2324694 TI - Hypertension control in a rural community. An assessment of community-oriented primary care. AB - To determine the effectiveness of a community-oriented primary care approach for the detection, treatment, and control of hypertension, data were analyzed from a survey of all 3094 adults living in a geographically well-defined rural community. Among the 2939 (96.1%) persons who completed the survey, 587 (20%) were found to meet study criteria for the diagnosis of hypertension. Hypertensive adults who identified a neighborhood health center with a community-oriented primary care philosophy as their source of care were more likely to have their disease detected, treated, and controlled than were hypertensive adults who identified other sources of care. The improved control was most evident for men and for blacks, but in every race-sex stratum, hypertensive patients of the neighborhood health center were more likely to be under control. Even when controlling in logistic models for age, race, and sex, identification of the neighborhood health center was associated with better control of hypertension (beta = 0.591, P = .004). In this rural community, community-oriented primary care delivered through a neighborhood health center appears to be associated with increased likelihood of detection, treatment, and control of hypertension. PMID- 2324695 TI - A prospective study of type A behavior and running injuries. AB - A prospective study was developed to examine whether personality factors predispose runners to injury. Forty runners who completed a type A behavior screening were followed for 1 year during which they documented their training mileage, injuries, and time lost from training because of injury. Runners with high scores on the type A behavior screening questionnaire experienced significantly more injuries, especially multiple injuries. Although not significant, high scorers lost nearly twice as much training time because of injury. No significant relationship was found between mileage and injury. The data suggest that a type A behavior score warrants consideration as a predictive risk factor when screening for potential running injuries. PMID- 2324696 TI - Sex of physician: patients' preferences and stereotypes. AB - Patients' preferences for physicians of a particular sex tend to skew sex distributions of clinical populations in training and practice settings. A study was developed to explore these preferences and potential reasons for them. Of 185 adult patients surveyed at four family practice residency clinics, 45% expressed a preference for sex of physician; 43% of women and 12% of men preferred a female physician, while 31% of men and 9% of women preferred a male physician. Patients who stated no overall preference often expressed one in specific clinical situations, eg, anal or genital examinations. Patients who preferred female physicians reported humane behaviors as more characteristic of female physicians, and those who preferred male physicians reported humane behaviors as more characteristic of men; patients who had no overall sex preference did not sex stereotype physicians on these behaviors (F = 59.34, P less than .01). Patients who preferred male physicians reported technical competence behaviors as more characteristic of male physicians; others did not sex stereotype physicians on these behaviors (F = 15.4, P less than .01). Patients rated humaneness and comprehensiveness as being of high priority, but no relationship was found between priorities for aspects of care and preferences for sex of physician. Areas for future investigation include assessing preferences in other populations and exploring sex differences in physician behavior during office encounters and correlating these differences with patient satisfaction. PMID- 2324697 TI - Should the complete medical record be computerized in family practice? An opposing view. AB - The goal of replacing the entire paper chart with an electronic record may be a subtle barrier to the spread of computer-stored medical records. The focus on needing to replace the current paper chart draws attention away from the benefits of having parts of the record stored in a computer retrieval form. Furthermore, the focus on total computerization implies a large initial and ongoing dollar commitment to replace the record completely. This commitment is unacceptable to most practices. No doubt, there are advantages of computerizing key patient data. Only key data should be computerized, however, not all data. Patient summaries containing the patient's demographics, medical problems, allergies, health maintenance status, and recent laboratory results can be used to generate needed prevention reminders as well as to do research (such as postmarketing drug surveillance) and management (such as being able to compare the utilization of various laboratory tests by physicians). Computer searches of these data can also be used to create patient target groups and to produce individualized labels and letters to contact patients. The computer medical record should complement, not replace, the traditional office record. The computer then can be used for a subset of the full record to take advantage of its unique power of retrieval and analysis. As a supplement to the record, the computer can be implemented in a modular step-by-step fashion rather than all at once with its attendant costs. This approach implies that the goal is more effective care of patients rather than a fascination with high technology. PMID- 2324698 TI - Mania or hypomania after withdrawal from antidepressants. PMID- 2324700 TI - References to religion in The Journal of Family Practice. Dimensions and valence of spirituality. PMID- 2324699 TI - Delayed analysis of urine. PMID- 2324701 TI - Compound versus multigranular exocytosis in peritoneal mast cells. AB - We have used the whole-cell patch-pipette technique to measure the step increases in the cell membrane capacitance (equivalent to the membrane area) caused by the fusion of secretory granules in degranulating murine mast cells. We have observed that up to 30% of the total membrane expansion caused by degranulation results from large fusion events that cannot be explained by the fusion of single secretory granules. These large events are observed mainly in the initial phase of a degranulation. We have developed a simple mathematical model for a mast cell to test whether these large events are caused by a stimulus-induced, granule-to granule fusion that occurs before their exocytosis (multigranular exocytosis). Our results suggest that the large fusion events are caused by the exocytosis of granule aggregates that existed before stimulation and that are located at the cell's periphery. We propose a novel mechanism by which granule aggregates can be formed at the periphery of the cell. This mechanism relies on the ability of a transiently fused granule ("flicker") to fuse with more internally located granules in a sequential manner. This pattern may result in the formation of larger peripheral granules that later on can fuse with the membrane. The formation of peripheral granule aggregates may potentiate a subsequent secretory response. PMID- 2324703 TI - Sterols of fungi responsible for superficial skin and nail infection. AB - Two groups of fungi isolated from human skin and nail are the dermatophytes Epidermophyton, Microsporum and Trichophyton species and the non-dermatophytes Hendersonula toruloidea and Scytalidium hyalinum. Examination of the sterol composition of these fungi by gas chromatography-mass spectrometry (GC-MS) identified five new sterols from dermatophytes, namely cholesterol, campesterol, episterol, fecosterol and sitosterol. These sterols, with ergosterol and brassicasterol, were also identified from extracts of H. toruloidea and S. hyalinum. Sterol patterns produced by GC-MS with selected ion recording of ten ions were analysed by principal components analysis using the SIMCA statistical package. The dermatophyte genera and species were not differentiated using this method, the similarity in sterol content reflecting the close taxonomic relationship of this group. H. toruloidea and S. hyalinum had similar sterol contents to each other, reinforcing the opinion that these fungi are related, although H. toruloidea form 3 was distinguished from forms 1 and 2. PMID- 2324702 TI - Effects of partial extraction of light chain 2 on the Ca2+ sensitivities of isometric tension, stiffness, and velocity of shortening in skinned skeletal muscle fibers. AB - Various functional roles for myosin light chain 2 (LC2) have been suggested on the basis of numerous and predominantly in vitro biochemical studies. Using skinned fibers from rabbit psoas muscle, the present study examines the influence of partial removal of LC2 on isometric tension, stiffness, and maximum velocity of shortening at various levels of activation by Ca2+. Isometric tension, stiffness, and velocity of shortening were measured at pCa values between 6.6 and 4.5 (a) in a control fiber segment, (b) in the same fiber segment after partial removal of LC2, and (c) after recombination with LC2. The extraction solution contained 20 mM EDTA, 20 or 50 mM KCl, and either imidazole or PO4(2-) as a pH buffer (pH 7.0). The amount of LC2 extracted varied with the temperature, duration of extraction, and whether or not troponin C (0.5 mg/ml) was added to the extraction solution. Extraction of 20-40% LC2 resulted in increased active tensions in the range of pCa's between 6.6 and 5.7, but had no effect upon maximum tension. The tension-pCa relationship was left-shifted to lower [Ca2+] by as much as 0.2 pCa units after LC2 extraction. At low concentrations of Ca2+, an increase in stiffness proportional to the increase in tension was observed. Readdition of LC2 to these fiber segments resulted in a return of tension and stiffness to near control values. Stiffness during maximal activation was unaffected by partial extraction of LC2. LC2 extraction was shown to uniformly decrease (by 25-30%), the velocity of shortening during the high velocity phase but it did not significantly affect the low velocity phase of shortening. This effect was reversed by readdition of purified LC2 to the fiber segments. On the basis of these findings we conclude that LC2 may modulate the number of cross bridges formed during Ca2+ activation and also the rate of cross-bridge detachment during shortening. These results are consistent with the idea that LC2 may modulate contraction via an influence upon the conformation of the S1-S2 hinge region of myosin. PMID- 2324704 TI - Purification of an inducible L-valine dehydrogenase of Streptomyces coelicolor A3(2). AB - Valine dehydrogenase (VDH) from Streptomyces coelicolor A3(2) was purified from cell-free extracts to apparent homogeneity. The enzyme had an Mr 41,000 in denaturing conditions and an Mr 70,000 by gel filtration chromatography, indicating that it is composed of two identical subunits. It oxidized L-valine and L-alpha-aminobutyric acid efficiently, L-isoleucine and L-leucine less efficiently, and did not act on D-valine. It required NAD+ as cofactor and could not use NADP+. Maximum dehydrogenase activity with valine was at pH 10.5 and the maximum reductive amination activity with 2-oxoisovaleric acid and NH4Cl was at pH 9. The enzyme exhibited substrate inhibition in the forward direction and a kinetic pattern with NAD+ that was consistent with a sequential ordered mechanism with non-competitive inhibition by valine. The following Michaelis constants were calculated from these data: L-valine, 10.0 mM; NAD+, 0.17 mM; 2-oxoisovalerate, 0.6 mM; and NADH, 0.093 mM. In minimal medium, VDH activity was repressed in the presence of glucose and NH4+, or glycerol and NH4+ or asparagine, and was induced by D- and L-valine. The time required for full induction was about 24 h and the level of induction was 2- to 23-fold. PMID- 2324705 TI - Chloramphenicol resistance in Streptomyces: cloning and characterization of a chloramphenicol hydrolase gene from Streptomyces venezuelae. AB - A 6.5 kb DNA fragment containing a chloramphenicol-resistance gene of Streptomyces venezuelae ISP5230 was cloned in Streptomyces lividans M252 using the high-copy-number plasmid vector pIJ702. The gene was located within a 2.4 kb KpnI-SstI fragment of the cloned DNA and encoded an enzyme (chloramphenicol hydrolase) that catalysed removal of the dichloroacetyl moiety from the antibiotic. The deacylated product, p-nitrophenylserinol, was metabolized to p nitrobenzyl alcohol and other compounds by enzymes present in S. lividans M252. Examination of the genomic DNA from several sources using the cloned 6.5 kb SstI fragment from S. venezuelae ISP5230 as a probe showed a hybridizing region in the DNA from S. venezuelae 13s but none in the DNA from another chloramphenicol producer, Streptomyces phaeochromogenes NRRLB 3559. The resistance phenotype was not expressed when the 6.5 kb SstI fragment or a subfragment was subcloned behind the lac-promoter of plasmid pTZ18R in Escherichia coli. PMID- 2324706 TI - Determination of guanine-plus-cytosine content of bacterial DNA by dual-laser flow cytometry. AB - A dual-laser flow cytometer was used to analyse different species of bacteria for the molar percentage of guanine-plus-cytosine (% G + C) without the need for DNA extraction or purification. Ethanol-fixed bacterial cells were stained with a combination of DNA-specific fluorochromes, Hoechst 33258 and chromomycin A3, which bind to AT- and GC-rich regions of DNA, respectively. A linear relationship (r = 0.99) was demonstrated between the log of the ratio of chromomycin A3 to Hoechst 33258 fluorescence and the log of the % G + C as determined by thermal denaturation (Tm) or buoyant density centrifugation (Bd) methods. Linearity was maintained for all bacterial species tested over the range of 28-67% G + C. A standard curve was constructed using five strains whose % G + C had been determined by other methods. From the equation describing this line, the % G + C values of nine other strains with known DNA base composition, together with the five strains used to construct the curve, were calculated using the chromomycin A3 to Hoechst 33258 ratio and were in agreement with values obtained by Tm, Bd or HPLC. The reproducibility of flow cytometric analysis (mean error 0.7% G + C) compared well with the reproducibility of other methods. Mixtures containing two species were also analysed. Two cell populations could be discerned in mixtures containing two species which differed in base composition by as little as 4% G + C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324708 TI - Cytotoxic T lymphocytes do not control lymphocytic choriomeningitis virus infection of BB diabetes-prone rats. AB - BioBreeding Worcester diabetes-prone (BBdp) rats develop insulin-dependent autoimmune-driven diabetes mellitus spontaneously and intravenous administration of 1 x 10(7) p.f.u. of lymphocytic choriomeningitis virus (LCMV) to young adult mice prevents disease. The virus is lymphotropic, binding to and replicating in such cells. BBdp rats fail to generate virus-specific major histocompatibility complex-restricted cytotoxic T lymphocyte (CTL) responses when challenged with this dose or other doses of LCMV, Pichinde virus or vaccinia virus. Yet such rats clear virus effectively and show no evidence of persistent infection. Associated with this clearance of virus and establishment of immunity is the production of neutralizing antibodies. In contrast, diabetes-resistant (BBdr) rats generate virus-specific CTL responses. Furthermore LCMV binds to fewer lymphoid cells of BBdr rats (in comparison to those of BBdp rats) and replicates in fewer lymphocytes (by one order of magnitude) from these rats. Thus, unlike mice in which CTLs play a dominant role in the control of LCMV infection, BBdp rats do not overcome this infection via CTLs. In addition, both the BBdp rats and their BBdr counterpart may provide useful models for determining whether or how individual lymphocyte subsets function in the induction of CTL responses, for the analysis of virus-induced immunosuppression and for the use of viruses or their products as therapeutic modalities. PMID- 2324707 TI - Host cell proteins required for measles virus reproduction. AB - We have developed a cell-free system derived from measles virus-infected cells that supported the transcription and replication of measles virus RNA in vitro. The data suggest that tubulin may be required for these reactions, since an anti beta-tubulin monoclonal antibody inhibited viral RNA synthesis and the addition of purified tubulin stimulated measles virus RNA synthesis in vitro. Tubulin may be a subunit of the viral RNA polymerase, since two different anti-tubulin antibodies, one specific for the beta- and another specific for the alpha-subunit of tubulin, coimmunoprecipitated the measles virus L protein as well as tubulin from extracts of measles virus-infected cells. Other experiments further implicated actin in the budding process during virus maturation, as there appeared to be a specific association of actin in vitro only with nucleocapsids that have terminated RNA synthesis, which is presumably a prerequisite to budding. PMID- 2324710 TI - The nucleotide sequence of the genomic RNA of kennedya yellow mosaic tymovirus Jervis Bay isolate: relationships with potex- and carlaviruses. AB - The nucleotide sequence of the genomic RNA of kennedya yellow mosaic tymovirus Jervis Bay isolate (KYMV-JB) has been determined. The genome of KYMV-JB is 6362 nucleotide residues long and encodes three major open reading frames. The genomic organization and the encoded proteins of KYMV-JB are very similar to those of three other tymoviruses that have recently been reported. Sequence comparisons revealed that the possible replicase proteins of tymoviruses are closely related to those of potexviruses and carlaviruses, suggesting a close evolutionary relationship among these viruses, despite differences in their genome organization and particle morphology. PMID- 2324709 TI - Characterization and cloning of the African horsesickness virus genome. AB - The dsRNA profiles of all nine African horsesickness virus (AHSV) serotypes were compared by agarose gel electrophoresis and PAGE. The agarose profiles were identical, but a unique profile was obtained for each of the nine serotypes by PAGE. Nine of the 10 dsRNA genome segments of AHSV-3 were cloned and the clones were used in dot-spot and Northern blot hybridization experiments to determine intra- and inter-serogroup nucleic acid similarities. Segments 1, 3, 4, 5, 7 and 8 were highly conserved in the AHSV serogroup and no genetic relationship with any of the other orbiviruses was observed. Of these segments 3, 5 and 8 showed the largest degree of cross-hybridization to the cognate genes of all the serotypes. These clones did not cross-hybridize to other orbiviruses such as epizootic haemorrhagic disease virus, bluetongue virus or equine encephalosis virus and are therefore recommended for use as group-specific probes for the identification of the AHSV serogroup. Genome segments 6 and 10 showed an intermediate degree of conservation, whereas segment 2 is serotype-specific and therefore probably codes for the outer capsid protein VP2. PMID- 2324711 TI - Differentiation of vaccine and wild mumps viruses using the polymerase chain reaction and dideoxynucleotide sequencing. AB - Parts of the F gene from 16 mumps viruses derived from vaccines and clinical isolates were amplified using the polymerase chain reaction and their nucleotide sequences were determined. Over a region of 111 nucleotides, eight regions of variability were detected with a maximum of six (5.4%) changes occurring between any two virus strains. The Jeryl Lynn and Urabe vaccine strains were clearly different from each other and from wild virus isolated from cases of non-vaccine associated mumps. In contrast, viruses isolated from the cerebrospinal fluid and throat in cases of meningitis and parotitis following vaccination with the Urabe strain were identical to this strain. We conclude that the vaccine was the source of these infections. PMID- 2324712 TI - Comparison of ground and aerial ultra-low volume applications of malathion against Aedes aegypti in Santo Domingo, Dominican Republic. AB - Efficacy of ground and aerial ultra-low volume (ULV) applications of 91% malathion at 438 ml/ha against Aedes aegypti in the Dominican Republic was evaluated using indoor collections, oviposition trapping and adult sentinel mortality rates. Ground compared to aerial ULV applications in this study were found to have a greater effect on Ae. aegypti when measured by the described sampling techniques. Neither application method provided the level of Ae. aegypti suppression believed necessary for control in the event of a dengue virus epidemic. PMID- 2324713 TI - Comparisons of different types and concentrations of alginates for encapsulation of Lagenidium giganteum (Oomycetes: Lagenidiales), a fungal pathogen of mosquito larvae. AB - Six different types of alginates used to encapsulate Lagenidium giganteum gave similar levels of fungal infection in Culex quinquefasciatus larvae. Initial infection levels when the capsules were immersed in water after 6 days of storage (15 and 25 degrees C) were 100% for all types of alginate and after 42 days of storage was 62-100%, depending on the type of alginate. Infectivity was 24-100% after the encapsulated fungus were left in water for 7 days and after 15 days was 0 to 26%, depending on the alginate. When 2 of the alginates were tested at different concentrations to give high, medium and low viscosity solutions, the fungus encapsulated using lower concentration alginate solutions usually gave the highest level of infectivity. PMID- 2324714 TI - Anopheles gambiae complex egg-stage survival in dry soil from larval development sites in western Kenya. AB - The potential for Anopheles egg survival in dry soil from larval development sites was investigated in western Kenya. A total of 230 dry soil samples collected in 1987, 1988 and 1989 yielded 126 first-instar Anopheles gambiae s.l. larvae from 2 to 5 days after flooding with water. These larvae were from dried animal hoofprints along streams (57.9%), from dried edges of permanent and temporary pools (41.3%) and from dried stream beds (0.8%). Larval density was 1.2 larvae/kg of soil from positive microhabitats in 1987 and 2.4 larvae/kg in 1988. Thirteen larvae from the 1989 soil samples, reared to adults, were identified by DNA probes as Anopheles gambiae sensu strictu (n = 6) and Anopheles arabiensis (n = 7). Experimentally, eggs from field-collected females remained viable up to 12 days for An. gambiae s.l. and 10 days for An. funestus. In western Kenya, egg viability in dry soil may represent a significant, short-term survival mechanism for 2 species of the An. gambiae complex. PMID- 2324715 TI - Host-seeking behavior and seasonal abundance of Culicoides paraensis (Diptera: Ceratopogonidae) in Brazil. AB - The ecology of Culicoides paraensis was studied with human bait collections at an agricultural research station near Belem and within 2 neighborhoods of Belem, Brazil, from 1977 to 1978. From collections conducted along transects that were centered on a house, we found most dense populations of host-seeking midges within and near the house. Host-seeking activity was least in areas fully exposed to sunlight compared to the levels of activity indoors and in shaded areas outside. Numbers of flies biting under shade trees and within the house increased during intervals of rain; concomitantly the levels of activity decreased in open areas. Seasonal population densities correlated with the pattern of rainfall, with a 2-month lag due to the long maturation time of immature C. paraensis. The effects of temperature and humidity on host-seeking activity are discussed. PMID- 2324716 TI - Prey selection by mosquitofish (Gambusia affinis) in California rice fields: effect of vegetation and prey species. AB - Mosquitofish are widely used for biological control of mosquito larvae in rice fields, but the presence of different types of vegetation or alternative arthropod prey affects the performance of the fish. Feeding experiments were conducted in 4 rice field vegetation zones. Overall, predation was maximal in young and mature rice, moderate in the submerged naiad vegetation, and minimal in areas of open water. A preference for fourth instar Culex tarsalis mosquito larvae over Daphnia pulex and the amphipod Hyalella azteca was demonstrated. Second nymphal stage corixid bugs, Cenocorixa sp., were avoided; a similar notonectid, Buenoa sp., was eaten in amounts comparable to the D. pulex and H. azteca. No preference between Culex tarsalis and Anopheles freeborni mosquito larvae was detected. PMID- 2324717 TI - Small plot test of sustained-release Altosid (methoprene) pellets against Aedes taeniorhynchus in brackish water. AB - Four percent methoprene pellets applied at a rate of 2.2 kg/ha effectively controlled adult Aedes taeniorhynchus emergence (93%) for over 3 weeks. Efficacy declined to 38% 4 weeks posttreatment. At a rate of 4.5 kg/ha, 95% control was maintained for 34 days with the exception of the 5th week when only 72% control was observed. PMID- 2324718 TI - New record for Aedes thelcter in Arizona. AB - Aedes thelcter was recorded for the first time in Arizona. Three specimens were collected at the Yuma Proving Ground in Yuma County during August 1988. This collection complements previous collections of this species near Bard, California, during 1987. PMID- 2324720 TI - Salt marsh mosquito control in Portsmouth, Rhode Island. AB - The Portsmouth, Rhode Island Mosquito Control Program used granular Bacillus thuringiensis var. israelensis to successfully control salt marsh mosquitoes in a 9 acre salt marsh while monitoring for, planning and implementing small scale open marsh water management in the marsh. Single season larviciding costs were roughly 4% that of contracted open marsh water management in this marsh. PMID- 2324719 TI - An improved applicator system for cellulose acetate electrophoresis. AB - An improved sample application system for cellulose acetate electrophoresis is described. This system features 30 interchangeable wells allowing sample reordering for side-by-side comparison of closely spaced electromorphs. PMID- 2324721 TI - Aedes aegypti surveillance in Tobago, West Indies (1983-88). AB - During 1983-88 Aedes aegypti were collected using larval surveys and ovitraps in Tobago, W.I. The main artificial containers used by Ae. aegypti were drums (35.4%) and small miscellaneous containers (23.4%). From a total of 15,600 ovitraps exposed, 183 ovitraps (1.3%) were positive, with 25 containing Ae. aegypti eggs and 158 with Haemagogus equinus eggs. No Aedes albopictus eggs were detected in Tobago during this study. PMID- 2324722 TI - Transmission of Plasmodium gallinaceum by adult Aedes aegypti infected as larvae. AB - Transmission of Plasmodium gallinaceum to chickens by adult mosquitoes eclosed from larvae that consumed infected adult mosquitoes was investigated. No malarial infections were observed in chicks fed on by mosquitoes that eclosed from larvae that had consumed crushed infected adult mosquitoes. Where cadavers with noncrushed thoraces were used, 3 of 4 chicks fed on by adult mosquitoes developed parasitemias ranging from 6 to 11% infected erythrocytes. PMID- 2324723 TI - Natural food and feeding behavior of Coquillettidia perturbans larvae. AB - The natural particulate food of larval Coquillettidia perturbans was studied through gut analysis using staining with 4'6-diamidino-2-phenylindole and epifluorescence microscopy. Bacteria (cocci, rods, spirochetes, purple bacteria and cyanobacteria), detritus, euglenoid protozoans and algae (desmids and diatoms) comprised the majority of particulate food, in order of abundance; other protozoans were rare, and hyphal forms (actinomycetes and fungi) were not observed. Abundance of food items in guts did not vary greatly among sampling months (June-December, 1987) or sampling sites. Fourth instars had a greater proportion of euglenoids and algae in their food than did younger instars. Observation of larval feeding behavior showed that fourth instars oriented upside down and fed mainly by suspension feeding, with occasional brushing from sediments and root surfaces. Microtrichia on filaments of the lateral palatal brushes of fourth instars indicated that the larvae were adapted to collect fine particles. PMID- 2324724 TI - Field efficacy of Vectobac-12AS and Vectobac-24AS against black fly larvae in New Brunswick streams (Diptera: Simuliidae). AB - The control of black fly larvae using 2 aqueous suspension formulations of Bacillus thuringiensis, serotype H-14 was evaluated in 6 trials on small and large sized streams in New Brunswick. Applications equivalent to 25 ppm (Vectobac 12AS) or 12.5 ppm (Vectobac-24AS) over a 1-min period resulted in 100% control of black fly larvae up to 3 km downstream of the application point. Over the 6 trials, effective carry was seen to increase with increased stream discharge which varied from as low as 0.8 m3/min in the small stream to 108.6 m3/min in the large stream. PMID- 2324725 TI - Control of Culex pipiens by Bacillus sphaericus and role of nontarget arthropods in its recycling. AB - Bacillus sphaericus was used to control Culex pipiens breeding in a water treatment settling basin near Montpellier, France. Four treatments with 4 liters/ha (3.6 lb/acre) of commercially available B. sphaericus formulation (Vectolex) reduced the larval population of Cx. pipiens with 50-600 spores of B. sphaericus/ml recorded in the treated portions of the water plant 14 days following the last treatment. Natural recycling of the bacteria was shown to take place at the water surface where germination of spores was evidenced. The appearance of vegetative forms of B. sphaericus may be linked to the passage through larval guts of several filter-feeding arthropods. PMID- 2324726 TI - Illustrated key to the female anopheline mosquitoes of Central America and Mexico. AB - An illustrated key to the female anopheline mosquitoes of Central America from western Panama to the southern border of the United States is presented with a taxonomic summary and distribution table. Thirty-nine species and one subspecies are treated: Chagasia (1), Anopheles (Anopheles) (25 and one subspecies), An. (Kerteszia) (2), An. (Lophopodomyia) (1), An. (Nyssorhynchus) (9) and An. (Stethomyia) (1). PMID- 2324727 TI - First record of DDT resistance in Anopheles darlingi. AB - DDT susceptibility of Anopheles darlingi was compared from the southeastern and northwestern regions of Colombia. Mosquitoes from southeastern Colombia (Puerto Lleras) were fully susceptible to DDT but in the northwest (Quibdo) LT50s were 14.3 times higher. This resistance appeared to be restricted to the Quibdo area. This is the first time that the DDT resistance has been detected in this important malaria vector. PMID- 2324728 TI - Seasonal changes of larval food and feeding of Chironomus crassicaudatus (Diptera: Chironomidae) in a subtropical lake. AB - The food of Chironomus crassicaudatus midge larvae in Lake Monroe, central Florida, was investigated from May 1981 to April 1982. Gut contents of larvae collected monthly from 16 stations in the lake were analyzed. Quantitative samples of water collected monthly at the mud-water interface at each station were analyzed for the larval food composition in the water. The larvae fed primarily on Cyanobacteria (blue-green algae). Blue-green algae were predominant in the water as well as in the larval guts, forming 63-87% and 52-84% of the total organisms observed in the water and in the larval guts, respectively. Populations of these organisms in the water were lowest in the summer. A highly significant relationship existed between the monthly mean percent of blue-green algae in the larvae and in the water. In general, the larvae were nonselective feeders in that the organisms enumerated in the water were also found in the gut. PMID- 2324729 TI - Efficacy of a juvenile hormone mimic, pyriproxyfen (S-31183), for mosquito control in dairy wastewater lagoons. AB - Pyriproxyfen (S-31183) was applied to dairy wastewater lagoons, during 1988, at 0.1 kg (AI)/ha in single and multiple applications which resulted in control of Culex spp. larvae for periods of 7 to 68 days. Length of the control period appeared to be related to water quality, with greater residual efficacy in more polluted sources. The AI apparently adsorbed onto organic debris where efficacy remained high in the lagoon even after water was pumped from the lagoon and replenished with untreated wastewater. Alternating treatments with control agents having a different mode of action is suggested to avoid selection of insecticide resistance. PMID- 2324730 TI - Effects of larval and adult diet plus mating/insemination upon ovarian development of laboratory-reared Anopheles pharoensis in Egypt. AB - A study was conducted in Egypt on the role of sugar and blood in oogenesis of Anopheles pharoensis. Also studied was the significance of mating vs. nonmating on oocyte maturity. Ovarian development in this species was influenced by larval diet. Those with inadequate larval nutrition emerged at Christophers' stage I and required either a sugar or blood meal to reach the resting stage. A subsequent complete blood meal was needed to take these females to stage V of Christophers (gravid). Females which emerged from well-nourished larvae were at the resting stage and became gravid via a single complete blood meal. Mating did not effect ovarian development since both inseminated and virgin females developed in like manner. At emergence, sugar feeding followed by a complete blood meal seems the best way for An. pharoensis to mature a first batch of eggs. PMID- 2324731 TI - Habitat pH characteristics of tree hole Culicoides (Diptera: Ceratopogonidae). AB - Ten species of Culicoides were collected from 166 tree holes at 20 widely separated geographic locations to assess relationships with habitat pH. Wet tree holes (containing standing water) had a mean pH of 7.46 while dry tree holes (no standing water) had a mean pH of 8.60. Culicoides arboricola, C. guttipennis and C. villosipennis occurred in wet tree holes that had mean pH values of 7.66, 7.95 and 7.31, respectively. Dry tree holes, where C. hinmani, C. elemae, C. paraensis, C. nanus, C. snowi and C. footei occurred, had pH values ranging from 8.13 to 9.08. Culicoides lahillei, a dry tree hole species, was collected from habitats with a pH range similar to the wet tree hole species. PMID- 2324732 TI - New method for removing type 2 copper from Rhus laccase. AB - A new procedure is described for preparing tree laccase that is missing the type 2 copper. The derivative has only about 5% of the activity of the native enzyme, and some, or all, of the residual activity could be due to traces of holoprotein. The type 1 copper is fully oxidized in the purified type-2-depleted protein, while the type 3 site is reduced to the extent of at least 85%. However, the type 3 coppers can be reoxidized by treatment with excess H2O2. Reconstitution is achieved by incubation with Cu(I), and the remetalated protein exhibits the activity and the spectral properties of the native enzyme. The type 2 copper is removed by dialysis against a redox buffer containing ferri- and ferrocyanide ions as well as EDTA. More than 25% of the total copper is removed from laccase during the procedure, but the type-2-depleted fraction is readily isolated by means of an ion-exchange column. The practical advantages of this procedure are described. Finally, the simplicity of the method raises hopes that the mechanism of depletion can be defined. PMID- 2324733 TI - Influence of aspirin and iron(III) tetrasulfonated phthalocyanine on bilirubin binding by human serum albumin. AB - The interaction of bilirubin with aspirin-modified human serum albumin (HSA) and the influence of iron tetrasulfonated phthalocyanine on bilirubin binding by the native protein has been studied by difference spectroscopy and circular dichroism measurements. Spectroscopic studies of the systems containing bilirubin and aspirin-modified HSA compared to the analogous systems with the native protein have shown that selective acetylation of albumin at lysine 199 inhibits bilirubin binding by this protein. In both cases, interaction between bilirubin and albumin leads to complex formation at a molar ratio of ligand to protein of 2:1. The studies of the reaction of bilirubin with fragments of albumin produced by reaction with CNBr have demonstrated that one of the strong bilirubin binding sites is located in the M fragment and is close to the high-affinity binding site of aspirin. The other one was found in fragment C. Acetylation of albumin brings about marked conformational change in the protein, which probably accounts for the decrease in its ability to react with anti-HSA antibody. Bilirubin does not change the secondary structure of albumin but, like aspirin, lowers its antigenicity. It has been suggested that the decrease in antigenic properties in this case results from cooperation of the closely neighboring antigenic and bilirubin-binding sites. The studies of the influence of iron(III) tetrasulfonated phthalocyanine on bilirubin binding by HSA suggest that there is no competition between strong sites for iron(III) tetrasulfonated phthalocyanine and bilirubin, but these compounds compete for some of the weaker sites. PMID- 2324734 TI - Choline uptake by cerebral capillary endothelial cells in culture. AB - A passage of choline from blood to brain and vice versa has been demonstrated in vivo. Because of the presence of the blood-brain barrier, such passage takes place necessarily through endothelial cells. To get a better understanding of this phenomenon, the choline transport properties of cerebral capillary endothelial cells have been studied in vitro. Bovine endothelial cells in culture were able to incorporate [3H]choline by a carrier-mediated mechanism. Nonlinear regression analysis of the uptake curves suggested the presence of two transport components in cells preincubated in the absence of choline. One component showed a Km of 7.59 +/- 0.8 microM and a maximum capacity of 142.7 +/- 9.4 pmol/2 min/mg of protein, and the other one was not saturable within the concentration range used (1-100 microM). When cells were preincubated in the presence of choline, a single saturable component was observed with a Km of 18.5 +/- 0.6 microM and a maximum capacity of 452.4 +/- 42 pmol/2 min/mg of protein. [3H]Choline uptake by endothelial cells was temperature dependent and was inhibited by the choline analogs hemicholinium-3, deanol, and AF64A. The presence of ouabain or 2,4 dinitrophenol did not affect the [3H]choline transport capacity of endothelial cells. Replacement of sodium by lithium and cell depolarization by potassium partially inhibited choline uptake. When cells had been preincubated without choline, recently transported [3H]choline was readily phosphorylated and incorporated into cytidine-5'-diphosphocholine and phospholipids; however, under steady-state conditions most (63%) accumulated [3H]choline was not metabolized within 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324735 TI - Apomorphine does not alter amphetamine-induced dopamine release measured in striatal dialysates. AB - Amphetamine facilitates the release of dopamine from nerve terminals, but the mechanisms underlying this effect have not been fully delineated. The present experiments were designed to test the extent to which amphetamine-induced dopamine release is dependent on impulse flow and autoreceptor function in dopaminergic neurons. Rats were pretreated with a low dose of apomorphine (0.05 mg/kg) to inhibit dopamine neuronal activity, and the striatal dopaminergic response to amphetamine (0.5 mg/kg) was assessed by in vivo dialysis in freely moving animals. Consistent with previous results, apomorphine alone substantially decreased, whereas amphetamine increased, striatal dialysate dopamine concentrations. However, whereas apomorphine pretreatment decreased the locomotor response to amphetamine, the amphetamine-induced increase in dialysate dopamine was unaffected. These results indicate that amphetamine-facilitated dopamine release is independent of neuronal firing and autoreceptor regulation, consistent with the putative accelerative exchange-diffusion mechanism of amphetamine induced dopamine release. Other possible mechanisms underlying the inhibitory effects of apomorphine on amphetamine locomotor activation are discussed. PMID- 2324736 TI - Ca2(+)-dependent, ATP-induced conversion of the [3H]hemicholinium-3 binding sites from high- to low-affinity states in rat striatum: effect of protein kinase inhibitors on this affinity conversion and synaptosomal choline transport. AB - Tritium-labeled hemicholinium-3 ([3H]HC-3) was used to characterize the sodium dependent high-affinity choline carrier sites in rat striatal preparations. In an earlier study, we had shown that [3H]HC-3 labels choline carrier sites with high and low affinities and had suggested that the low-affinity sites represent "functional" carrier sites. The objective of the present study was to examine the mechanisms involved in the regulation of the two affinity states of [3H]HC-3 binding. Here, we demonstrate that these two affinity states are totally interconvertible; addition of 0.1 mM ATP in the binding assay medium quantitatively converted all the binding sites to the low-affinity state, whereas addition of 1 mM beta,gamma-methylene 5'-ATP quantitatively converted all the binding sites to the high-affinity state. Preincubation of the tissue (for 15 min at 37 degrees C) before the binding assay also converted the binding sites to the high-affinity state, whereas supplementation of the assay medium with ATP (0.5 mM) again induced expression of the low-affinity state of the binding sites. This effect of ATP was found to be selective for this nucleotide. Neither ADP (1 mM) nor cyclic AMP could mimic such an effect. Other nucleotide triphosphates--CTP (0.5 mM) and GTP (0.5 mM)--also could not substitute for ATP. GTP, however, caused nearly a 35% reduction in the number of binding sites, accompanying a loss of the low-affinity component of binding. This effect of GTP was also shared by 5'-guanylylimidodiphosphate but not by GDP or cyclic GMP. This ATP-dependent low affinity conversion of [3H]HC-3 binding sites requires divalent metal ions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324737 TI - Extracellular striatal dopamine and its metabolites during transient cerebral ischaemia. AB - Severe cerebral ischaemia has been repeatedly shown to provoke a massive increase in striatal extracellular dopamine (DA). These experiments were undertaken to determine the duration of the DA increase produced by transient ischaemia, and the fate of the released DA during recirculation. Experiments were performed in anaesthetised rats subjected to 20 min of cerebral ischaemia, followed by 80 min of reperfusion, before cardiac arrest. Measurements of catechols were made in the striatum using in vivo differential pulse voltammetry (DPV), each 4 min, throughout the experiment and for 60 min after cardiac arrest. DPV data were substantiated with intracerebral dialysis; 20-min dialysate samples were analysed for DA and homovanillic acid (HVA) using HPLC. In 6 of 11 rats, ischaemia induced a massive DA release in the striatum, resulting in a marked increase in extracellular levels (350-1,200%), which persisted throughout ischaemia. DPV and intracerebral dialysis demonstrated that DA was totally cleared from the extracellular space within minutes of reperfusion, whereas both its acidic metabolites (3,4-dihydroxyphenylacetic acid and HVA) increased slightly. These results indicate that DA released during 20-min ischaemia is rapidly cleared during reperfusion, mainly via reuptake. In the five other rats, only a relatively small and transient increase in the DPV catechol peak was detectable, cleared before the end of ischaemia, probably reflecting less severe ischaemia; small or no changes were detectable in the corresponding dialysate. The latter data suggest that different change(s) in the nigrostriatal dopaminergic system may occur, according to the severity of ischaemia. PMID- 2324738 TI - Alpha-bungarotoxin binds to human acetylcholine receptor alpha-subunit peptide 185-199 in solution and solid phase but not to peptides 125-147 and 389-409. AB - The nicotinic acetylcholine receptor (AChR) of human skeletal muscle has a reducible disulfide bond near the neurotransmitter binding site in each of its alpha-subunits. By testing a panel of overlapping synthetic peptides encompassing the alpha-subunit segment 177-208 (containing cysteines 192 and 193) we found that specific binding of 125I-labelled alpha-bungarotoxin (alpha-BTx) was maximal in the region 185-199. Binding was inhibited by unlabelled alpha-BTx greater than d-tubocurarine greater than atropine greater than carbamylcholine. Peptide 193 208 did not bind alpha-BTx, whereas 177-192 retained 40% binding activity. Peptides corresponding to regions 125-147 (containing cysteines 128 and 142) and 389-409, or peptides unrelated to sequences of the AChR failed to bind alpha-BTx. No peptide bound 125I-alpha-labelled parathyroid hormone. The apparent affinity (KD) of alpha-BTx binding to immobilized peptides 181-199 and 185-199 was approximately 25 microM and 80 microM, respectively, in comparison with alpha-BTx binding to native Torpedo ACh receptor (apparent KD approximately 0.5 nM). In solution phase, both peptides effectively competed with solubilized native human AChR for binding of alpha-BTx, and peptide 185-199 showed little evidence of dissociation after 24 h. Peptides that bound alpha-BTx did so when sulfhydryls were reduced. Cysteine modification, by N-ethylmaleimide or acetamidomethylation, abolished alpha-BTx-binding activity. The data implicate the region of cysteines 192 and 193 in the binding of neurotransmitter to the human receptor. PMID- 2324739 TI - Phosphate-dependent monoclonal antibodies to neurofilaments and Alzheimer neurofibrillary tangles recognize a synthetic phosphopeptide. AB - Five phosphate-dependent monoclonal antibodies to the neurofilament heavy polypeptide bound strongly to a phosphorylated synthetic peptide, which contains a single Lys-Ser-Pro sequence that occurs in human neurofilaments. Three of the antibodies label Alzheimer's disease neurofibrillary tangles and two do not, suggesting that in tangles an epitope similar to the peptide is available to some but not all of the antibodies. In addition, some antibodies were found to be more affected than others by enzymatic dephosphorylation of the antigen, but because all the antibodies bound the same synthetic phosphopeptide they do not bind to mutually exclusive phosphorylation sites. Instead the more phosphate-dependent antibodies might bind the phosphate group more directly, as suggested by their inhibition by inorganic phosphate and free phosphoserine. PMID- 2324740 TI - Determination of N-acetylaspartic acid in human cerebrospinal fluid by gas chromatography-mass spectrometry. AB - N-Acetyl-L-aspartic acid was identified and determined in human cerebrospinal fluid. The concentration in lumbar fluid was about 2 nmol/ml and about 20 nmol/ml in ventricular fluid. There was no difference between healthy subjects and schizophrenic patients. PMID- 2324741 TI - Further studies on the changes of chicken brain gangliosides during prenatal and postnatal life. AB - The developmental profiles of the gangliosides and those of the fatty acids and long-chain bases of the total ganglioside mixture of the brain of chicken were followed from the 10th day of incubation to the 63rd posthatching day. One O acetylated polysialoganglioside that seems specific of the earlier embryonic stage and up to 21 alkali-stable components could be recognized by high resolution two-dimensional TLC procedures and quantified by computer-assisted two dimensional TLC densitometry. Besides a number of gangliosides identified by co chromatography with reference standards, 10 were of unidentified structure, and within these 4 did not belong to the gangliotetrahexosyl series. Throughout embryonic life, the ceramide portion of gangliosides was found to contain the long-chain base species with 18 carbons. Those with 20 carbons, approximately 10% of the total, were found to be present only after hatching. PMID- 2324742 TI - Production of 1,2-diacylglycerol in PC12 cells by nerve growth factor and basic fibroblast growth factor. AB - The addition of nerve growth factor (NGF) or basic fibroblast growth factor (bFGF) to PC12 cells prelabeled with [3H]inositol and preincubated for 15 min in the presence of 10 mM LiCl stimulated the production of inositol phosphates with maximal increases of 120-180% in inositol monophosphate (IP), 130-200% in inositol bisphosphate (IP2), and 45-50% in inositol trisphosphate (IP3) within 30 min. The majority of the overall increase (approximately 85%) was in IP; the remainder was recovered as IP2 and IP3 (approximately 10% as IP2 and 5% as IP3). Under similar conditions, carbachol (0.5 mM) stimulated about a 10-fold increase in IP, a sixfold increase in IP2, and a fourfold increase in IP3. The mass level of 1,2-diacylglycerol (DG) in PC12 cells was found to be dependent on the incubation conditions; in growth medium [Dulbecco's modified Eagle's medium (DME) plus serum], it was around 6.2 mol %, in DME without serum, 2.5 mol %, and after a 15-min incubation in Dulbecco's phosphate-buffered saline, 0.62 mol %. The addition of NGF and bFGF induced an increase in the mass level of DG of about twofold within 1-2 min, often rising to two- to threefold by 15 min, and then decreasing slightly by 30 min. This increase was dependent on the presence of extracellular Ca2+, and was inhibited by both phenylarsine oxide (25 microM) and 5'-deoxy-5'-methylthioadenosine (3 mM). Under similar conditions, 0.5 mM carbachol stimulated the production of DG to the same extent as 200 ng/ml NGF and 50 ng/ml bFGF. Because carbachol is much more effective in stimulating the production of inositol phosphates, the results suggest that both NGF and bFGF stimulate the production of DG primarily from phospholipids other than the phosphoinositides. PMID- 2324743 TI - Molecular species of choline and ethanolamine phospholipids in rat cerebellum during development. AB - The molecular species composition of rat cerebellar phospholipid subclasses has been studied by HPLC after phospholipase C treatment and dinitrophenyl derivatization. During rat cerebellum development (3-90 days postpartum), cholinephosphoglycerides and ethanolamine phosphoglycerides represented approximately 80% of all phospholipids, with their relative amount changing after 1 month. Among ethanolamine phosphoglycerides, the molar ratio of diacylglycerophosphoethanolamine (diacylGPE) to alkenylacylGPE decreased from approximately 1.4 at 3 days to approximately 0.5 after 10 days. The phospholipids investigated contained up to 12 different molecular species. The rate of accumulation of the various molecular species of diacylglycerophosphocholine (diacylGPC), diacylGPE, and alkenylacylGPE during cerebellar development allowed a classification into three main groups. The overall increase of the molecular species of the first group (6-diacylGPC, 5-diacylGPE, and 4-alkenylacylGPE) was approximately 18-fold between 3 and 90 days, with a faster rate of accumulation between 3 and 30 days. Those of the second group (3-diacylGPC, 5-diacylGPE, and 5 akenylacylGPE) increased by approximately 45-fold during the same developmental period, at a slow rate before day 15 and a faster one thereafter. The molecular species of the third group (3-alkenylacylGPE) increased by greater than 250-fold between 3 and 90 days, at a very slow rate before day 21 and more quickly thereafter. The different rates of accumulation of the components of the three groups during cerebellar development suggest a preferential location of the first group in membranes of neuronal perikaryons, glial cells, and synaptosomal structures. Those of the second group appear to be located in both synaptosomal membranes and myelin sheets, and those of the third group can be considered as myelin markers. PMID- 2324744 TI - Selective alterations in presynaptic cytomatrix protein organization induced by calcium and other divalent cations that modulate exocytosis. AB - Rises in intracellular calcium cause several events of physiological significance, including the regulated release of neuronal transmitters. In this study, the effects of divalent cations on the structural organization of cytomatrix in presynaptic terminals was examined. [35S]Methionine-radiolabeled guinea pig retinal ganglion cell cytomatrix proteins were axonally transported [in slow component b (SCb) of axonal transport] to the neuron terminals in the superior colliculus. When the peak of radiolabeled cytomatrix proteins reached the terminals, synaptosomes containing the radiolabeled cytomatrix proteins were prepared. Approximately 40% of each SCb protein was soluble after hypoosmotic lysis of the radiolabeled synaptosomes in the presence of divalent cation chelators. Lysis of synaptosomes in the presence of calcium ions over a range of concentrations, however, caused a dramatic decrease in solubility of the presynaptic SCb proteins. The cytoplasmic effects may result from a calcium dependent condensation of cytoplasm around presynaptic terminal membrane systems. There are two major presynaptic SCb proteins (at 60 and 35 kDa), that exhibited exceptional behavior: they remained as soluble in the presence of calcium as under control conditions, suggesting that they were relatively unaffected by the mechanism causing the decrease in SCb protein solubility. Also examined were the effects of other alkaline earth and transition metal divalent cations on the presynaptic SCb proteins. PMID- 2324745 TI - Cholesterol synthesis is down-regulated during regeneration of peripheral nerve. AB - The discovery of apolipoprotein E synthesis and secretion by injured peripheral nerve to the hypothesis that endoneurial apolipoprotein E serves to salvage degenerating myelin cholesterol. This salvaged cholesterol could then be reutilized by Schwann cells during remyelination via uptake through low-density lipoprotein receptors. As a test of this hypothesis, we measured the rate of cholesterol synthesis in rat sciatic nerve endoneurium during development and at various times following a crush injury at 50 days of age. In control nerves [14C]acetate incorporation into cholesterol and 3-hydroxy-3-methylglutaryl-CoA reductase activity were closely linked throughout development, indicating that reductase activity in nerve, as in other tissues, is a good indicator of cholesterol's synthetic rate. In the crushed nerves cholesterol synthesis fell to nearly zero during the first week after the crush. There was a partial recovery during the second to fourth weeks, but unlike that of other lipids, cholesterol synthesis remained well below control nerve values throughout most of the 15-week post-crush period examined. Thus, cholesterol synthesis is at very low levels during the myelination of regenerating axons. These results are consistent with a receptor-mediated down-regulation of cholesterol synthesis by lipoproteins, and would be expected if Schwann cells were utilizing an external source of cholesterol as postulated above. PMID- 2324746 TI - Interaction of asymmetric and globular acetylcholinesterase species with glycosaminoglycans. AB - Chicken muscle and retina, and rat muscle asymmetric acetylcholinesterase (AChE) species were bound to immobilized heparin at 0.4 M NaCl. Binding efficiency was between 50 and 80% for crude fraction I A-forms (AI; muscle), and nearly 100% for fraction II A-forms (AII; muscle and retina). Antibody-affinity-purified AI-forms (chicken) were, however, quantitatively bound to heparin-agarose gels, whereas diisopropylfluorophosphate-inactivated high-salt extracts partially prevented the binding of both AI and AII AChE forms, thus suggesting the presence in crude AI extracts of heparin-like molecules interfering with the tail-heparin interaction. All bound A-forms were progressively displaced from the heparin-agarose columns by increasing salt concentrations, with maximal release at about 0.6 M. They were also efficiently eluted by heparin solutions (1 mg/ml), other glycosaminoglycans being much less effective. Chicken globular AChE forms (G-forms, both low-salt soluble and detergent-soluble) also bound to immobilized heparin in the absence of salt. Stepwise elution with increasing NaCl concentrations showed maximal release of G-forms at 0.15 M, all globular forms being totally displaced from the column at 0.4 M NaCl. Heparin (1 mg/ml) had the same eluting capacity as 0.4 M NaCl, whereas other glycosaminoglycans were only marginally effective. We conclude that the molecular forms of AChE in these vertebrate species interact with heparin, at salt concentrations that are characteristic for asymmetric and globular forms. Within the A and G molecular form groups, no differences were found in the behavior of the different fractions or subtypes, provided that the enzyme samples were free of interfering molecules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324747 TI - Developmental changes in the activity of enzymes of purine metabolism in rat neuronal cells in culture and in whole brain. AB - The activities (Vmax) of several enzymes of purine nucleotide metabolism were assayed in premature and mature primary rat neuronal cultures and in whole rat brains. In the neuronal cultures, representing 90% pure neurons, maturation (up to 14 days in culture) resulted in an increase in the activities of guanine deaminase (guanase), purine-nucleoside phosphorylase (PNP), IMP 5'-nucleotidase, adenine phosphoribosyltransferase (APRT), and AMP deaminase, but in no change in the activities of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenosine deaminase, adenosine kinase, and AMP 5'-nucleotidase. In whole brains in vivo, maturation (from 18 days of gestation to 14 days post partum) was associated with an increase in the activities of guanase, PNP, IMP 5' nucleotidase, AMP deaminase, and HGPRT, a decrease in the activities of adenosine deaminase and IMP dehydrogenase, and no change in the activities of APRT, AMP 5' nucleotidase, and adenosine kinase. The profound changes in purine metabolism, which occur with maturation of the neuronal cells in primary cultures in vitro and in whole brains in vivo, create an advantage for AMP degradation by deamination, rather than by dephosphorylation, and for guanine degradation to xanthine over its reutilization for synthesis of GMP. The physiological meaning of the maturational increase in these two ammonia-producing enzymes in the brain is not yet clear. The striking similarity in the alterations of enzyme activities in the two systems indicates that the primary culture system may serve as an appropriate model for the study of purine metabolism in brain. PMID- 2324749 TI - Murine neuroblastoma cells express ganglioside binding sites on their cell surface. AB - The ability of S20Y cholinergic, and N115 adrenergic, murine neuroblastoma cells to adhere to immobilized gangliosides was studied. Viable S20Y cells adhered more strongly to GM1-coated plastic wells than to those coated with GM2, GD1a, or GT1b. The oligosaccharide portion of GM1 inhibited adherence of S20Y cells to GM1 coated wells, indicating that the carbohydrate moiety of GM1 bore the recognition site. Analysis of S20Y cell adherence to wells coated with derivatives of GM1 indicated that the cells did not adhere to asialo-GM1 and adherence to the methyl ester or de-N-acetyl derivatives was significantly reduced. Expression of the GM1 binding sites by S20Y cells appears to be density dependent; cells harvested at the confluent stage of growth were more adherent than those harvested at the preconfluent stage. Trypsin treatment of the S20Y and N115 cells resulted in a loss of binding to GM1-coated wells, suggesting that the cell surface GM1 binding site is a protein. In contrast, N115 cells showed no significant difference in their adherence to wells coated with GM1, GD1a, GT1b, Gal-Cer, asialo-GM1, or the methyl ester of GM1 when assayed under the same conditions as those imposed on the S20Y cells. The N115 cells did show a reduction in adherence to GM2-coated wells, suggesting that they recognized the terminal galactosyl moiety. PMID- 2324748 TI - Precursors and metabolites of norepinephrine in sympathetic ganglia of the dog. AB - 3,4-Dihydroxyphenylalanine, dopamine, epinephrine, 3,4-dihydroxyphenylglycol, and 3,4-dihydroxyphenylacetic acid as well as norepinephrine were measured in dog lumbar sympathetic ganglia. The responses of these compounds to several classes of stimuli were investigated using an isolated time-resolved superfusion system. Nonselective (i.e., amphetamine and high K+) and receptor-mediated selective (oxotremorine) stimuli were used to evoke releases. The overflows of all compounds were measured by HPLC with electrochemical detection. The efficiency of each stimulus was estimated by normalizing the amount of evoked release to the total neurotransmitter pool when the stimulus was applied; i.e., fractional release was calculated. Overflows of all compounds except 3,4 dihydroxyphenylalanine were enhanced by a 10-min 100 microM amphetamine stimulus, and each of the catecholamine pools (dopamine, norepinephrine, and epinephrine) was affected to the same degree. By contrast, the 3,4-dihydroxyphenylalanine and dopamine pools were more readily releasable than the norepinephrine pool with a 10-min 80 mM K+ stimulus, and these releases were Ca2+ dependent. Epinephrine was released in preference to norepinephrine by a 10-min 1 mM oxotremorine stimulus. The data suggest the existence of at least three types of neurons in dog lumbar ganglia and are consistent with previous histological observations. PMID- 2324750 TI - Production of platelet-activating factor from rat cerebellar granule cells in culture. AB - Platelet-activating factor (PAF) is a potent lipid mediator implicated in various pathological conditions, including CNS neuronal injury. However, the production of PAF by mammalian CNS neurons has not as yet been demonstrated. In the present study, we demonstrate that PAF is produced by cultured rat cerebellar granule cells. PAF was identified on the basis of chemical and enzymatic characteristics, biological activities with washed rabbit platelets, and behavior on TLC and HPLC. PAF was detected both in the cells and in the incubation medium, a result indicating the release of PAF from cultured neurons. The amount of PAF produced during a 30-min incubation was as follows: 1.02 +/- 0.10 and 0.93 +/- 0.09 pmol/4 X 10(7) cells in incubation buffer and cells, respectively (n = 10). The calcium ionophore A23187 (2.5 microM) had only a mild stimulatory effect on PAF production, a finding indicating that the neuron-generated PAF might be synthesized mainly by the de novo pathway of PAF production. PMID- 2324751 TI - Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. I. Abducens palsy. AB - Fifty one patients with abnormalities of horizontal gaze were studied with magnetic imaging of the brain (MRI) and eye movement recordings to identify the loci of lesions responsible for isolated abducens palsy, conjugate gaze palsy and different types of internuclear ophthalmoplegias. The lesions responsible for a particular disorder were identified by overlapping enlarged drawings of the individual scans at comparable brain-stem levels and identifying the areas where the abnormal MRI signals intersected. A statistical procedure was devised to exclude the possibility that the areas of overlap occurred by chance. In this paper, the findings in the group of patients with VI nerve palsy are reported since the location of their lesions could be predicted from known anatomy, so validating the procedure. The results were independently obtained with the overlapping technique and the statistical procedure and showed that the lesions were located in a region corresponding to the posterior part of the abducens fasciculus. This confirms that central lesions producing isolated lateral rectus weakness spare the abducens nuclei. The agreement between the procedures used and earlier clinical and experimental results suggest that the method we describe can be applied to locate the site of lesions on MRI scans in other groups of patients with more complex gaze disorders. PMID- 2324753 TI - Pathological stretch reflexes on the "good" side of hemiparetic patients. AB - The reflex EMG responses from a tendon tap or an imposed, medium amplitude (30 degrees), stretch at a range of stretch velocities have been recorded from the triceps and biceps muscles of normal human subjects and in both the affected and "unaffected" arms of hemiparetic patients under relaxed conditions. In the hemiparetic arm, exaggerated tendon jerks were, as expected, observed in both muscles. The response of the biceps to elbow extension was also exaggerated compared with normal values and displayed both an additional earlier component and a much reduced velocity threshold. The triceps, in contrast, showed depressed responses to elbow flexion, with a much higher velocity threshold than normal subjects. Furthermore, on the supposedly "unaffected" side of the hemiparetic subjects, the reciprocal pattern was seen, with depression of the biceps response and a raising of its threshold, along with considerably exaggerated responses in the triceps including earlier components not seen in the normal subjects. The increased excitability of the flexor musculature on the spastic side may be paralleled by increases in activity in the segmental pathways responsible for modulation of agonist/antagonist activity in the ipsi and contralateral limb, leading to an inhibition of the ipsilateral extensors and contralateral flexors and excitatory input to the contralateral extensors. Thus the "good" side of hemiparetic patients also receives pathological changes, and studies of the mechanisms of spasticity should avoid the use of the "unaffected" side of hemiparetic subjects as a control for monitoring pathological reflexes. PMID- 2324752 TI - Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. II. Gaze palsy and internuclear ophthalmoplegia. AB - The site of lesions responsible for horizontal gaze palsy and various types of internuclear ophthalmoplegia (INO) was established by identifying the common areas where the abnormal MRI signals from patients with a given ocular-motor disorder overlapped. Patients with unilateral gaze palsy had lesions in the paramedian area of the pons, including the abducens nucleus, the lateral part of the nucleus reticularis pontis caudalis and the nucleus reticularis pontis oralis. Patients with abducens nucleus lesions showed additional clinical signs of lateral rectus weakness. Lesions responsible for bilateral gaze palsy involved the pontine tegmental raphe. Since this region contains the saccadic omnipause neurons, this finding suggests that damage to omnipause cells produces slowing of saccades rather than opsoclonus, as previously proposed. All INOs, regardless of the presence of impaired abduction or convergence, had similar MRI appearances. Frequently the lesions in patients with INO, were not confined to the medial longitudinal fasciculus (MLF) but also involved neighbouring structures at the pontine and mid-brain levels. There was a statistically significant association between the clinical severity of the INO and the presence of abnormal abduction or convergence. The findings suggest that the lesions outside the MLF, which may affect abducens, gaze or convergence pathways, are responsible for the presence of features additional to INO, depending on the magnitude of functional disruption they produce. PMID- 2324754 TI - Severity of Parkinson's disease is a risk factor for peak-dose dyskinesia. AB - Fifty four patients with idiopathic Parkinson's disease receiving levodopa therapy were studied. Thirty three of these patients displayed peak-dose dyskinesia. Neither the duration of Parkinson's disease nor the duration of levodopa therapy discriminated between patients with and patients without peak dose dyskinesia. Consequently, these criteria could not determine whether the first appearance of peak-dose dyskinesia depends on the duration of Parkinson's disease--a factor that is related to the severity of the disease--or on the duration of levodopa therapy. A subgroup of nineteen patients with unilateral or unequivocally asymmetrical peak-dose dyskinesia was examined 12 hours after withdrawal of levodopa. A levodopa testdose provoked unilateral or unilateral preponderant peak-dose dyskinesia which always involved the most severely affected side and which also happened to be the side of onset of the disease. This demonstrates that the severity of Parkinson's disease is the main risk factor for peak-dose dyskinesia. PMID- 2324755 TI - Abnormality in the cavernous sinus in three patients with Tolosa-Hunt syndrome: MRI and CT findings. AB - Three patients with Tolosa-Hunt syndrome (THS) were examined using computed tomography (CT), orbital venography and magnetic resonance imaging (MRI). CT of the brain showed no definite abnormality in two patients, right optic nerve enlargement and an abnormal area around the orbital apex in one patient. Orbital venography showed an occlusion of the superior ophthalmic vein in one of three patients. MRI showed an abnormal soft tissue area in the cavernous sinus, with intermediate to high signal intensity on T1- or intermediate weighted images. There was clinical improvement following corticosteroid therapy and the abnormal soft tissue on MRI decreased in volume and in signal intensity, although this was equivocal in one patient. Thus MRI proved to be useful in demonstrating lesions in the cavernous sinus in patients with THS. PMID- 2324756 TI - Sensory and cognitive event-related potentials in myalgic encephalomyelitis. AB - Myalgic Encephalomyelitis (ME) is a form of post viral fatigue syndrome resulting in myalgia and fluctuating fatiguability. Symptoms reflecting central nervous system dysfunction are common and include muscle weakness, headache, sensory disturbances, poor short term memory and impairment of concentration. In view of the fact that sensory and cognitive disturbances are experienced by many patients objective evidence was sought with multi-modality sensory evoked potentials and auditory event-related cognitive potentials in a group of ME patients both with and without the enteroviral antigen, VP1 test positive. The auditory brainstem, median nerve somatosensory and pattern reversal checkerboard visual potentials were normal for all 37 patients tested. In contrast to the sensory potentials significant differences in the mean latencies of the cognitive potential N2 and P3 were found. Reaction times were also significantly prolonged but the performance in terms of error was not significantly affected. No significant difference emerged in any of the parameters for the VP1 test. P3 was abnormal in latency or amplitude in 36% of the VP1 positive patients for the frequency discrimination task and 48% for the more difficult duration discrimination task. The abnormalities indicate attentional deficits in some patients and slower speed of information processing in others. The prolonged latencies observed in these patients have not been observed in patients with depression in many other studies. PMID- 2324757 TI - Pseudodementia twelve years on. AB - This paper reports a longitudinal study of 19 patients diagnosed as having pseudodementia more than a decade earlier. In only one patient was the earlier diagnosis changed to definite dementia and, in this patient, there were strong indicators that such a diagnosis should have been made initially. In a second patient, dementia could not be excluded. The remaining patients did not show evidence of a dementing illness and the courses of the illnesses resembled the primary psychiatric disorders responsible for the pseudodementia. The results validate the clinical utility of the term "pseudodementia". PMID- 2324758 TI - Onset and offset of electromyographic (EMG) silence in asterixis. AB - The onset and offset of electromyographic (EMG) silence were studied physiologically by silent period locked averaging method (SPLA) combined with a computer-assisted method for detecting EMG changes in 11 patients with asterixis of various aetiologies. The onset followed the EMG discharge which was closely associated with a sharp wave probably generated by the motor cortex in three patients. No EEG activity could be shown to be related to the offset of EMG silence in every patient. Jerky movement of asterixis was temporally related to the offset of EMG silence rather than the onset. PMID- 2324760 TI - Persistent segmental cerebral artery constrictions in coital cephalgia. PMID- 2324759 TI - Pure agraphia after deep left hemisphere haematoma. AB - Pure agraphia is reported following haematoma in the left centrum semiovale sparing both parietal and frontal cortices. There was total inability to produce graphemes in the absence of limb apraxia. The lesion is assumed to have prevented linguistic and graphemic systems from gaining access to the frontal motor programme. PMID- 2324761 TI - Dysphagia due to a pharyngeal mucocoele mimicking myasthenia. PMID- 2324762 TI - Korsakoff's psychosis. PMID- 2324763 TI - Xanthochromia in subarachroid haemorrhage. PMID- 2324764 TI - Pathology of neuroleptic malignant syndrome. PMID- 2324766 TI - Giant axonal neuropathy: studies with sulfhydryl donor compounds. AB - Giant axonal neuropathy (GAN) is a disorder characterized pathologically by distal neurofilament-filled bulbous swellings in axons, and widespread collection of intermediate filaments, including masses of vimentin filaments in cultured skin fibroblasts. A morphologically similar neurofibrillary disorder is produced by acrylamide and the toxic hexacarbons, agents which bind to thiol groups. We report, in GAN fibroblasts, inhibition of vimentin filament aggregation by dithiothreitol and penicillamine, sulfhydryl donor compounds which stabilize thiols. In addition, we describe clinical improvement in a GAN patient treated with penicillamine, despite earlier progressive disease. These findings support the hypothesis of disordered thiol metabolism in GAN, and open up avenues for further research. PMID- 2324765 TI - Effects of in vitro hyperthermia on fatty acids of red blood cells and plasma lipids from patients with multiple sclerosis. AB - Heparinized blood from 43 patients with multiple sclerosis (MS) and 43 controls matched for age, sex and race were incubated at 42 degrees C for 24 h. The hematocrit values were determined before and after heating. The plasma and red blood cells (RBC) were separated and the plasma free fatty acids (FFA), total neutral lipids (NL; which included the triglycerides and cholesteryl esters), phospholipids (PL), and RBC lipids from 24 patients and 24 controls were isolated. The total amounts of the various FFA in the plasma and the relative percentage fatty acid compositions of the various FFA, NL, ester-linked fatty acids of plasma PL, RBC lipids as well as those of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fractions of RBC lipids were determined by gas liquid chromatography (GLC). The hematocrit values were significantly higher in heated samples from both MS and controls. The results of fatty acid analyses from 24 pairs of heated and unheated MS and controls showed that the concentrations of total FFA and most of the fatty acids increased significantly in the heated plasma of both MS and control samples, compared to the respective unheated plasma samples. When the FFA values were expressed as relative percentage compositions, the results showed significant increases in palmitic, arachidonic and adrenic acids and significant decreases in oleic, linoleic and linolenic acids in the heated samples from MS and controls compared to the corresponding unheated samples. In NL the relative percentages of linoleic and arachidonic acids were significantly higher in the heated samples from both MS and controls, while in the PL, the percentages of linoleic acid were lower in the heated samples from both MS and controls, when compared to the corresponding unheated samples. The fatty acid compositions of the RBC lipids showed highly significant increases in palmitic plus palmitoleic, stearic and oleic acids and significant decreases in linoleic and most of the polyunsaturated acids in the heated MS samples compared to the unheated MS samples. In contrast, the fatty acid compositions of the RBC lipids from heated controls showed significant increase in only palmitic plus palmitoleic acids and significant decreases in linoleic and arachidonic acids, compared to the values from unheated controls. The results show that the RBC membranes from MS were more affected by the heat than those of control RBC, indicating possible differences between blood from MS patients and controls. PMID- 2324767 TI - Brainstem auditory evoked potentials in Wilson's disease. AB - Twelve patients with Wilson's disease, aged 11-25 years, underwent brainstem auditory evoked potential (BAEP) study. The results were correlated to clinical, neuroradiological and laboratory data. Ten had prominent to severe neurological manifestations, suggestive of involvement of one or several CNS structures, and 2 were neurologically free. All had evidence of abnormal copper metabolism, and 8 had CT scan evidence of brain atrophy, or hypodense areas in basal ganglia, or both. The 2 patients without neurological manifestations as well as one with neurological signs had normal BAEP. One patient with neurological signs had increased N1 latency due to cochlear hearing loss, but normal interpeak intervals, while 8 of 10 patients with prominent neurological symptoms and signs had abnormal BAEPs (prolongation of NIII-NV interpeak interval). The value of NIII-NV interpeak interval correlated with the number of different neurological signs (neurological score) attributable to involvement of different CNS structures (r = 0.64 at P = 0.001). Abnormal BAEPs do not seem to be an early finding in Wilson's disease. PMID- 2324768 TI - Therapeutic possibilities of chronic low frequency electrical stimulation in children with Duchenne muscular dystrophy. AB - To evaluate the therapeutic possibilities of chronic electrical stimulation, muscle function studies and quantitative tests of physical assessment were used to monitor the response of quadriceps femoris to prolonged low frequency stimulation. Comparative studies of the maximum voluntary and electrically elicited responses of muscles of young ambulant children with Duchenne muscular dystrophy, when compared to those of normal children's muscles, revealed lower values of maximum voluntary contraction, significant slowing (P less than 0.001) of mean relaxation times and a higher resistance to fatigue testing. Intermittent chronic low frequency stimulation resulted in a significant (P less than 0.01) increase in mean maximum voluntary contraction of the stimulated muscles compared with the mean force exerted by the unstimulated control muscles. There are clear therapeutic possibilities for the use of chronic low frequency stimulation in these children. PMID- 2324769 TI - Werdnig-Hoffmann disease: myosin isoform expression not arrested at prenatal stage of development. AB - It has been suggested, on the basis of mostly morphological and some biochemical evidence, that defective innervation of muscle of patients with Werdnig-Hoffmann (WH) disease results in maturational arrest of the fibers at a stage comparable to 20-week gestational muscle. Therefore, with the use of recently developed and characterized, myosin-isoform-specific monoclonal antibodies (McAbs), an immunocytochemical study of muscle of 6 children with Werdnig-Hoffmann disease was done to determine if the pattern of expression of myosin heavy chain isoforms (MHC) in these fibers was similar to that of 20-week gestation muscle. This work showed that the MHC isoform expression in the muscle of the children with WH did not mimic that seen in 20-week gestation muscle since only a few fibers (less than 1-11%) in each specimen expressed prenatal MHC as detected by reactivity to McAb, ALD 180 (specific for a prenatal MHC) whereas virtually all of the fibers from 20-week gestation muscle were strongly reactive with ALD 180. The majority of the fibers expressed either adult fast MHC or adult slow MHC similar to that seen in normal muscle, although some co-expressed multiple MHC isoforms. Our results indicate that the difference of adult MHC isoforms in the muscle fibers of WH patients either proceeds in the absence of innervation or that denervation of muscle fibers is subsequent to the neural input required to initiate myosin isoform transitions to the adult isoforms. PMID- 2324770 TI - Motor unit potentials in a mildly affected muscle in amyotrophic lateral sclerosis. AB - Quantitative analysis of motor unit potentials (MUPs) with spike triggering and averaging was performed from the mildly affected brachial biceps muscle of 18 patients with amyotrophic lateral sclerosis (ALS) and of 18 age-matched controls. The total MUP duration was only 6% higher in ALS patients than in controls (P less than 0.05) while the durations of the main MUP and fast components were prolonged by 63% and 194% (P less than 0.001), respectively. The number of satellites, number of fast components and amplitude were also significantly increased in the ALS group. It is concluded that determination of the duration and number of fast components and the MUP amplitude will sensitively pick up mild neurogenic affection of the brachial biceps muscle. PMID- 2324771 TI - Limb girdle syndromes. Clinical, morphological and electrophysiological studies. AB - The clinical syndrome of slowly progressive proximal limb and limb girdle muscular weakness and atrophy, or limb girdle syndromes (LGS), has a diverse aetiology. Several of the congenital, mitochondrial and other metabolic myopathies and spinal muscular atrophies are recently recognized causes of LGS. Thus the position of limb girdle muscular dystrophy (LGMD) as a discrete entity in the nosology of muscle disease deserves reappraisal. We have therefore reevaluated our experience of 33 patients in this light. Detailed clinical, electrophysiological, and pathological studies including autopsies in 2 cases, were performed. As a result we are confident that LGMD does exist as a sporadic or autosomal dominant (2 families) or recessive condition (2 families). There are therefore probably at least 2 distinct genotypes. Typical LGMD (18 patients in our series) is characterized by slowly progressive symmetrical proximal upper and lower limb girdle weakness and atrophy, elevation of the serum creatine kinase at some stage, dystrophic or less severe myopathic muscle lesions on biopsy, and myopathic EMG findings. Two minor subgroups of LGMD were identified in our series with similar clinical and laboratory features but distinguishable by the development of either facial (4 patients) or by distal limb muscle involvement (3 patients). A further group of patients with sporadic LGS (5 patients) had slowly progressive proximal symmetrical upper and lower limb-girdle weakness and atrophy with myopathic or neurogenic features on either EMG or muscle biopsy so that the precise characterization was difficult. Two of these patients had distal limb muscle involvement and contractures. One patient had upper limb-girdle muscle atrophy with normal lower limbs. A disorder affecting muscle, nerve or both remains a possibility in these cases. PMID- 2324772 TI - Is there a characteristic dermal involvement in amyotrophic lateral sclerosis? PMID- 2324773 TI - Functional impairment in Mexican Americans and non-Hispanic whites with diabetes. AB - There are virtually no data available describing the functional status of diabetic individuals. We therefore measured functional status using the Sickness Impact Profile (SIP) in 393 diabetic subjects and 486 nondiabetic control subjects identified from the San Antonio Heart Study, a population-based study of diabetes among Mexican Americans and non-Hispanic whites. The SIP is a validated instrument that assesses the presence of health-related behavior changes and activity restrictions in 12 different categories. Functional impairment, defined as a SIP score of 2.0% or greater, was present among 36.6% of diabetic subjects. Following adjustments for age, Mexican Americans were 1.63 times more likely to experience functional impairment that non-Hispanic whites, although this difference was not statistically significant (95% confidence interval: 0.92 2.89). The categories in which subjects experienced impairment varied widely, but the category with the highest prevalence of impairment was "eating" (greater than 40%). The prevalence of functional impairment was 45.9% among diabetic subjects with vascular complications, 31.8% among diabetic subjects without complications, and 16.7% among nondiabetic control subjects. Among all diabetic subjects impairment increased with age, duration of diabetes, fasting glucose, and BMI, and with insulin use and the presence of hypertension. In a multiple logistic regression model these factors (with the exception of insulin use) remained associated with the presence of functional impairment even after adjustment for the presence of vascular complications. If the factors responsible for this excess of functional impairment can be identified, an intervention might be designed which can lead to improvement in the quality of life for diabetic individuals. PMID- 2324774 TI - Health behavior and urinary tract infection in college-aged women. AB - We conducted a case-control study to examine the associations between various behavioral risk factors and urinary tract infection among college-aged women. Cases were collected from a University Health Service, and were compared to Health Service controls and to a population-based control group. Sexual intercourse, diaphragm use, and urinating after sexual intercourse were each associated with urinary tract infection (UTI). The magnitude of the association of diaphragm use with UTI was reduced when urination habits around sexual intercourse were considered. PMID- 2324775 TI - A comparison of multivariable mathematical methods for predicting survival--I. Introduction, rationale, and general strategy. AB - This paper and the two following papers (Parts I-III) report an investigation of performance variability for four multivariable methods: discriminant function analysis, and linear, logistic, and Cox regression. Each method was examined for its performance in using the same independent variables to develop predictive models for survival of a large cohort of patients with lung cancer. The cogent biologic attributes of the patients had previously been divided into five ordinal stages having a strong prognostic gradient. With stratified random sampling, we prepared seven "generating" sets of data in which the five biologic stages were arranged in proportional, uniform, symmetrical unimodal, decreasing exponential, increasing exponential, U-shaped, or bi-modal distributions. Each of the multivariable methods was applied to each of the seven generating distributions, and the results were tested in a separate "challenge" set, which had not been included in any of the generating sets. The research was intended not merely to compare the performance of the multivariable methods, but also to see how their performance would be affected by different statistical distributions of the same cogent biologic attributes. The results, which are presented in the second and third papers, were compared for selection of independent variables and coefficients, and for accuracy in fitting the generating sets and the challenge set. PMID- 2324776 TI - A comparison of multivariable mathematical methods for predicting survival--II. Statistical selection of prognostic variables. PMID- 2324777 TI - A comparison of multivariable mathematical methods for predicting survival--III. Accuracy of predictions in generating and challenge sets. AB - This paper concludes a study of "performance variability" when four methods of multivariable analysis--multiple linear regression, discriminant function analysis, multiple logistic regression, and two arrangements of Cox's proportional hazards regression--were applied to the same stratified random samples of "generating sets" containing seven different statistical distributions of cogent biologic attributes in a composite staging system for a large cohort of patients with lung cancer. Each model developed from the generating sets was also applied for predictions in a previously sequestered "challenge set". Across the different generating sets, the multivariable methods showed good agreement with one another in the stepwise choice of first two powerful predictor variables, but not in the sequence of subsequent choices or in the standardized coefficients assigned to the same collection of "forced" variables. In concordance of predictions for individual patients in the generating sets, the overall proportions of disagreement for pairs of methods ranged from 0 to 28%, and kappa values ranged from 0.49 to 1.00. The accuracy of individual predictions showed relatively similar results when the different methods were applied to the same generating set. Across the generating sets, the different methods showed similar total results but substantial variations in predictions for alive and dead patients. When the models from the generating sets were applied for predictions in the challenge set, the results showed an analogous pattern: similar accuracy within models for overall and live/dead predictions, but substantial variations in live/dead predictions across models derived from different generating sources. The results showed that the multivariable methods often had good agreement with one another in predictions for groups but not for individual persons; and that no single method was superior to the others or to the composite staging system. We conclude that multivariable analytic methods may be most effective and consistent if used to find the few most powerful predictor variables, omitting the many other variables that may be "statistically significant" but less cogent. The powerful predictors may sometimes be best constructed, before the analysis begins, as composite variables containing appropriate unions or ordinal arrangements of elemental candidate variables. PMID- 2324779 TI - Geographical variations in blood pressure in British men and women. AB - Geographical variations in blood pressure have been studied using an automatic sphygmomanometer in 2596 men and women aged 25-29, 40-44 and 55-59 living in nine British towns. In males aged 40-59, systolic blood pressure showed a range in age adjusted town means of 9.0 mmHg (p less than 0.05); in females the difference of 8.6 mmHg was not significant (p = 0.14). Mean arterial pressure (MAP) and diastolic at age 40-59 were significantly different between towns for both sexes. Differences at age 25-29 were of a similar magnitude, and the mean town blood pressures at 25-29 correlated highly with those at 40-59 [systolic; males r = 0.74 (p less than 0.05), females r = 0.65 (p = 0.059)]. The ranking of town blood pressures in an earlier study was reflected in the present study, but stronger associations were observed with cardiovascular mortality. It is concluded that geographical blood pressure variations in Britain are established by age 25-29 years. PMID- 2324778 TI - Prevalence and correlates of family dysfunction and poor adjustment to chronic illness in specialty clinics. AB - This study estimated the prevalence of poor adjustment and family dysfunction among three chronically ill clinic patient populations and assessed the biological, situational, social and psychological variables which most explained poor adjustment. Recently referred subjects were approached and 216 chronically ill subjects (from oncology, rheumatology and gastroenterology clinics) completed a Meaning of Illness Questionnaire, the McMaster Family Assessment Device, and the Psychosocial Adjustment to Illness Self-report Scale. In addition, information describing their biological, disease and socioeconomic status was obtained from the clinic record. Respondents were generally representative of other new referrals to the clinics (ineligible for the subsequent trial) in disease characteristics but uniformly came from a more advantaged socioeconomic situation and were better adjusted to illness. Subjects from the three clinics were comparable on meaning, family function and adjustment variables. The proportion of subjects with family dysfunction was 30% and with poor adjustment to illness was 36%, high by community standards. Nevertheless, healthy family functioning and high levels of positive adjustment to chronic illness prevailed and were remarkably similar across clinic settings. Severity or type of disease was not related to adjustment outcomes nor to the level of observed disability. Rather, as hypothesized, meaning given the illness, followed by family function, and disability variables combined to explain 57% of the variance in adjustment outcomes. An intervention designed to improve family function and the meaning given illness was judged suitable. PMID- 2324780 TI - Measuring the impact of trauma care on survival: rates of preventable death, effectiveness, and efficacy. AB - This paper focuses on the appropriateness of outcome measures to evaluate trauma care. The preventable death rate (PDR), based on the study of deceased patients only, has been the traditional measure of the impact of trauma care on improving the survival of patients with severe trauma. Another measure frequently used in other ares of evaluation research is the effectiveness rate--i.e. the survival rate in the total population of severe trauma patients. Because both the PDR and the effectiveness rate vary with the proportion of patients who would die even under conditions of optimal care, these two measures can be misleading. We illustrate their inadequacy by using published data on the impact of regionalization of trauma care. We propose the use of a third outcome measure of the impact of trauma care on survival, the efficacy rate--i.e. the survival rate among severe trauma patients with a potential for survival. Evaluation of trauma care should also measure outcomes other than survival and need not be restricted to patients with the most severe trauma. Evaluation of trauma care therefore requires outcome measures, such as the efficacy rate, which are based on the population at risk of manifesting the outcome of interest. PMID- 2324781 TI - Bypass coronary surgery. PMID- 2324782 TI - Identification of high risk groups for breast cancer by means of logistic models. AB - In order to identify high risk groups for breast cancer, unconditional multiple logistic regression models based on 5 widely recognized and easily identifiable risk factors (age at menarche, at menopause and at first birth, family history of breast cancer and body mass index) were applied to a large dataset including 2085 cases and 1936 controls aged 50 or over derived from two unmatched hospital-based case-control studies conducted in Italy. Although various models provided an excellent fitting, both on the whole dataset and using a training-testing approach to a priori identified separate subset, the observed extent of variation in breast cancer risk between highest and lowest decile of the distribution was limited to a factor 2. This indicates that the 5 variables considered did not allow identification of subgroups with substantially elevated risk of breast cancer to have practical implications for screening/prophylactic treatment purposes. PMID- 2324783 TI - Rapid method for estimating the risk of acutely controversial side effects of prescription drugs. AB - When controversy suddenly erupts about the risk of using a prescription drug, there is an urgent need for fast methods of risk estimation. Some unexpected side effects of prescription drugs are indications for the prescribing of another kind of drug. If the risk of such a side-effect is high, it should be reflected in clustered prescribing of the side-effect-alleviating drug in sequence with the side-effect-causing drug. The risk of drug-attributable side-effects can be estimated by comparing average incidences of initial prescriptions for the side effect-alleviating drug before, during, and long after the dispensing of the presumed side-effect-causing drug. We monitored computerized, complete drug dispensing records of anonymous outpatients for use of flunarizine, an anti vertigo/anti-migraine drug that case reports had suggested causes mental depression and/or Parkinsonism. Among 1284 patients who eventually got flunarizine during a 31 month period, 1 in 7 was started on an anti-depressant before or long after flunarizine; only 1 in 82 might be said to have been started on an anti-depressant because of flunarizine. There was no evidence that anti Parkinson drugs were started because of flunarizine, though the numbers are small. The analysis takes only a few days, and can help set bounds on risks of the subset of adverse drug reactions that are themselves indications for use of other drugs. PMID- 2324784 TI - Factors associated with smoking in low-income pregnant women: relationship to birth weight, stressful life events, social support, health behaviors and mental distress. AB - Since low-income women are at increased risk of having low birth weight infants, factors associated with birth weight among such groups have special relevance. Cigarette-smoking has emerged as an important predictor of low birth weight due to intrauterine growth retardation and pre-term delivery. After confirming the relation of smoking with birth weight, we examined the association of smoking with sociodemographic factors, attitudes towards pregnancy, health behaviors, stressful life events, social support, and symptoms of mental distress in a cohort of 458 Central Harlem women. We found that social support, stress and mental health were associated with smoking behavior but not directly with birth weight. These findings suggest that programs designed to modify health behaviors such as smoking during pregnancy must also take into account such characteristics of the women and their environments which may make behavioral change difficult. Moreover, programs aimed at fostering better health behaviors to improve pregnancy outcome may have to extend beyond the current pregnancy, as indicated by an association between prior adverse pregnancy outcome and smoking in the current pregnancy. PMID- 2324785 TI - Thyroid nodularity after childhood irradiation for lymphoid hyperplasia: a comparison of questionnaire and clinical findings. AB - Ionizing radiation is a well-established cause of thyroid cancer and nodularity, however, important questions relating to the magnitude of the risk following low dose medical exposures remain unresolved. To address these issues, we conducted a follow-up study of 1590 individuals treated between 1938 and 1969 with X-rays for childhood lymphoid hyperplasia (av. thyroid dose = 24 cGy) and 1499 individuals treated with surgery only. Thyroid nodularity was determined from self administered questionnaires completed by 1195 irradiated and 1063 surgically treated subjects and from clinical examinations of 602 irradiated and 457 non irradiated subjects. A much higher relative risk (RR) for radiation-induced thyroid nodules was estimated from the questionnaire than from the clinical examination data, 15.8 and 2.7, respectively. (The corresponding estimates of excess RR per cGy were 64 and 7%). Analysis of the examination data revealed a strong dose-response relationship, similar excess RR/cGy for males and females, and an inverse relationship with age at exposure. Although the thyroid gland is one of the most sensitive organs to the neoplastic effects of radiation, the radiation-induced risk of thyroid nodularity reported from questionnaire studies may over-estimate the true risk. PMID- 2324786 TI - Haematologic parameters and pregnancy outcome. A prospective cohort study in the third trimester. AB - The relationship between haematologic parameters and pregnancy outcome was investigated in a prospective study, taking important covariates into consideration. A questionnaire asking information about smoking, alcohol consumption and iron intake was completed by a consecutive series of 796 ambulatory singleton pregnant women at 31-32 weeks of gestation. Subsequently, haematologic parameters were measured. After delivery, birth weight, gestation length and blood pressure values during pregnancy were abstracted from the obstetricians' records. Low birth weight (less than 2.500 g) and preterm birth (less than 37 weeks), were significantly more frequently seen in women with high haemoglobin (greater than or equal to 8.0 mmol/l) or high haematocrit (greater than 38%) values, with Mantel-Haenszel odds ratios varying from 2.4 to 4.2. Also a high erythrocyte count (greater than or equal to 4.5/pl) was correlated with low birth weight, while for mean corpuscular volume (MCV) no such relationships were found. Pregnancy induced hypertension was positively associated with haemoglobin, haematocrit and erythrocyte count, but could not fully explain the relationships between these parameters and adverse outcomes. Using multiple logistic regression with low birth weight and or preterm birth as the dependent variable, the effect of haematocrit still was demonstrable after controlling for smoking, hypertension, parity, alcohol consumption and iron intake. These results are in agreement with the hypothesis that a higher blood viscosity is a risk factor for suboptimal placenta-perfusion. PMID- 2324787 TI - The WHO principles for registering causes of death: suggestions for improvement. AB - In the ongoing 10th revision of the International Classification of Diseases, the WHO's rules for registering causes of death are revised. Previous studies have shown that deficiencies in the WHO's rules and basic concepts for registering causes of death impair the quality of cause-of-death statistics. The purpose of the present paper is to elucidate some of these shortcomings and to make suggestions for improvement. Also, the purpose of the WHO's definition of 'the underlying cause of death' is discussed, and a modification suggested. Suggestions are also made for new definitions of the four basic WHO concepts, 'causes of death', 'the underlying cause of death', 'direct cause' and 'contributory conditions'. At the end an account is given of the proposals made within the WHO for changes in the rules for registering causes of death. PMID- 2324790 TI - Prescription-event monitoring: methodology and recent progress. AB - Event monitoring was first suggested 25 years ago as a way of detecting adverse reactions to drugs. Prescription-event monitoring (PEM), which has been developed by the Drug Safety Research Unit, is the first large-scale systematic post marketing surveillance method to use event monitoring in the U.K. PEM identifies patients, who have been prescribed a particular drug, and their doctors from photocopies of National Health Service prescriptions which are processed centrally in England. A personalized follow-up questionnaire ("green form") is mailed to each patient's general practitioner, usually on the first anniversary of the initial prescription, asking for information about the patient, especially any "events" that he or she may have experienced since beginning treatment with the drug. The methodology of PEM is presented, together with examples of analyses that can be performed using results from recent studies. The problems and benefits of PEM are discussed. PMID- 2324788 TI - Longitudinally measured blood pressure, antihypertensive medication use, and cognitive performance: the Framingham Study. AB - The relation of longitudinally measured blood pressure to cognitive performance in the absence of clinically diagnosed cerebrovascular disease was investigated in the Framingham Study. In 1976-1978, neuropsychologic testing was administered to 1993 participants aged 55-89 years. Performance on an education-adjusted composite of these tests was examined in relation to measures of chronicity of hypertension as well as the average systolic and average diastolic blood pressure. All analyses were stratified by antihypertensive medication use during the 2 years prior to cognitive testing and adjusted for age, sex, occupation, alcohol consumption, and participation rate in prior examination cycles. Among subjects on drug therapy for hypertension, there was no association between cognitive performance and longitudinally measured blood pressure. The proportion of cycles in which hypertension was present and average systolic and diastolic blood pressure had a significant inverse relation with cognitive performance only in the group not on antihypertensive drug therapy. However, among subjects on antihypertensive medication at earlier cycles, there was a highly significant graded relation between cognitive impairment and the probability of being off medication at the time of testing. These results suggest that hypertension related subclinical vascular disease is not an important cause of cognitive impairment in the elderly. Cognitive impairment may, however, be associated with a reduced adherence to drug treatment regimens. PMID- 2324789 TI - Measuring quality of life in cardiac spouses. AB - The purpose of this study was to develop an objective instrument to measure changes in quality of life of spouses of post-myocardial infarction (MI) patients, and to determine its responsiveness and validity. A 70-item list of potential areas of concern was compiled; the 25 most frequent and important concerns comprised the framework of the final questionnaire. The questions on the Quality of Life Questionnaire for Cardiac Spouses (QL-SP) were categorized into the Emotional Function Dimension (EFD), and the Physical and Social Function Dimension (PSFD). Subjects (n = 39) completed the QL-SP and a battery of established questionnaires at home, 1-2 weeks post-hospital discharge for the patient, and 8 weeks later. Scores on the QL-SP between visits were improved for both the EFD (t = 5.56, p less than 0.001), and the PSFD (t = 6.11, p less than 0.001). The agreement between predicted and observed relationships between the dimension changes and other index changes, as measured statistically by a kappa with Cicchetti weights, was significant (kappa w = 0.43, p = 0.0012). The QL-SP appears to be responsive and valid, and may be useful in evaluating clinical and research intervention strategies. PMID- 2324791 TI - The media and the AIDS crisis. A conference of Oregon journalists. PMID- 2324792 TI - The clinical picture. PMID- 2324793 TI - Aneurysms of the ophthalmic segment. A clinical and anatomical analysis. AB - The clinical, radiographic, and anatomical features in 80 patients with ophthalmic segment aneurysms were reviewed, and were categorized according to a presumed origin related to the ophthalmic (41 cases) or superior hypophyseal (39 cases) arteries. There was a marked female predominance (7:1) and high incidence of multiple aneurysms (45%) within this population. Clinical presentations included subarachnoid hemorrhage in 23 cases (29%) and visual deficits in 24 (30%); five patients exhibited both hemorrhage and visual loss. Twenty-eight aneurysms were incidentally identified. Ophthalmic artery aneurysms arose from the internal carotid artery (ICA) just distal to the ophthalmic artery, pointed superiorly or superomedially, and (when large) deflected the carotid artery posteriorly and inferiorly, closing the siphon. Abnormalities relating to vision were not identified until the aneurysm realized giant proportions. The optic nerve was typically displaced superomedially, which restricted contralateral extension until late in the clinical course; unilateral nasal field loss was seen in 12 patients. Nine patients had bilateral ophthalmic artery aneurysms which were often clipped via a unilateral craniotomy. Superior hypophyseal artery aneurysms arose just above the dural ring from the medial bend of the ICA, at the site of perforator origin to the superior aspect of the hypophysis, and had no direct association with the ophthalmic artery. The carotid artery was usually located lateral or superolateral relative to the aneurysm. These lesions could extend medially beneath the chiasm (suprasellar variant), producing a clinical and computerized tomography picture similar to a pituitary adenoma, or they could extend ventrally to burrow beneath the anterior clinoid process (paraclinoid variant). Preoperative categorization of these lesions according to their likely branch of origin provides excellent correlation with visual deficits and operative findings, and has allowed the author to clip 52 of 54 lesions, with very low operative or visual morbidity. PMID- 2324794 TI - Management of dural arteriovenous malformations of the anterior cranial fossa. AB - Eight patients with dural arteriovenous malformations (AVM's) of the anterior cranial fossa are presented, and the pertinent literature is reviewed. Unlike cases of dural AVM's in other locations, sudden massive intracerebral hemorrhage was the most frequent reason for presentation. Other symptoms included tinnitus, retro-orbital headache, and a generalized seizure. The malformations were supplied consistently by the anterior ethmoidal artery, usually in combination with other less prominent feeding vessels. The lesion's venous drainage was through the superior sagittal sinus via a cortical vein; in addition, in two cases a subfrontal vein drained the AVM. A venous aneurysm was encountered near the site of anastomosis with the dural feeder in most cases, and was found in all patients who presented with hemorrhage. The AVM was obliterated surgically in six patients, with favorable results achieved in five. One patient died postoperatively from a pulmonary complication. Because of their anatomy and proclivity for hemorrhage, these vascular malformations represent a unique group of dural AVM's. Surgical management of anterior fossa dural AVM's carries low morbidity, and is indicated when the lesions have caused hemorrhage or when there is an associated venous aneurysm. PMID- 2324796 TI - Vascular anomalies associated with aneurysms of the anterior communicating artery: microsurgical observations. AB - Direct operations were performed on 206 patients with aneurysms of the anterior communicating artery (ACoA) using a bifrontal craniotomy and an interhemispheric approach. A total of 44 (21.4%) of these patients had vascular anomalies in the vicinity of the ACoA; these included a median artery of the corpus callosum (MACC) in 27 cases (13.1%), duplication of the ACoA in 20 (9.7%), and duplication of the A1 segment of the anterior cerebral artery in one (0.5%). A retrospective study of the angiograms indicated that diagnosis of the A1 or ACoA duplication was not possible; only 11 (41%) of the 27 MACC's were easily identified, while eight (30%) could not be diagnosed. The majority of the cases of ACoA aneurysms with MACC (81.5%) showed trifurcation of the ACoA, A2, and MACC. The operative results in the patients with MACC did not differ significantly from the results of the entire ACoA aneurysm series. From the above study it is concluded that, regardless of whether a vascular anomaly has been identified preoperatively, ACoA aneurysm surgery should be undertaken with that possibility in mind. A bifrontal craniotomy and an interhemispheric approach has the advantage of allowing for a wide operative field and the attainment of a good understanding of the vascular structures near the ACoA. It is particularly useful in cases of vascular anomaly in this region. PMID- 2324795 TI - Influence of intraoperative antibiotic choice on the incidence of early postcraniotomy seizures. AB - Because of a suspicion that intraoperative penicillin antibiotics might be causing early postoperative seizures in craniotomy patients, a deliberate effort was initiated in 1987 to avoid these agents in favor of nonpenicillin antibiotics. This permitted a retrospective comparison of the incidence of early postoperative seizures in craniotomy patients who did and who did not receive intraoperative penicillins. Records of patients treated between July 1, 1984, and July 1, 1985, and between July 1, 1987, and July 1, 1988, were reviewed, for a total of 1316 procedures. There were no seizures in the 323 patients who underwent suboccipital craniectomy. However, among the 993 patients receiving supratentorial procedures there were 30 with seizures within the first 6 hours postoperatively, 19 of which were generalized seizures. The incidence of early seizures was 4.7% (20 cases) of the 427 patients given penicillins and only 1.8% (10 cases) of the 566 not given penicillins (p less than 0.01). Since patients undergoing surgery for intractable seizures have a high incidence of early postoperative seizures (11 of 92 in this series, or 12%), creation of a subgroup eliminated these from consideration but did not alter the relationship of penicillins to early seizures (p less than 0.02). The authors conclude that intraoperative (and early postoperative) penicillin antibiotic administration should be avoided, if possible, in patients undergoing craniotomy for supratentorial pathology. PMID- 2324797 TI - Experience in the management of myelomeningocele in Puerto Rico. AB - The medical records of 128 children with myelomeningocele who were treated at the Pediatric University Hospital, Puerto Rico Medical Center, from January, 1980, to July, 1985, were reviewed retrospectively. The medical and surgical management during the first hospitalization of these children was studied in detail for predefined parameters. The average age at the time of myelomeningocele repair was 6.6 days. Statistical analysis showed that repair of the myelomeningocele defect before 48 hours of age did not reduce the occurrence of ventriculitis. The incidence of ventriculitis secondary to the management of the myelomeningocele lesion was 12.5%. Complications after repair of the myelomeningocele (including skin flap necrosis, cerebrospinal fluid leaks, and wound infection) were present in 43.8% of the patients who developed ventriculitis and in 19.0% of those who did not. This observation is statistically significant (p = 0.03) and indicates that complications of healing after myelomeningocele repair represent the most significant risk factor for the development of ventriculitis. PMID- 2324798 TI - Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection. AB - To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise "unsafe" doses of radiation in patients with CNS neoplasms. PMID- 2324799 TI - Enhancement of the efficacy of x-irradiation by pentobarbital in a rodent brain tumor model. AB - Radiation therapy is an important component of brain tumor treatment, but its efficacy is limited by its toxicity to the surrounding normal tissue. Pentobarbital acts as a cerebral radioprotectant, but the selectivity of its protection for the central nervous system has not been demonstrated. To determine if pentobarbital also protects tumor against ionizing radiation, five groups of Fischer 344 rats were observed after exposure to varying combinations of the presence or absence of implanted tumor, pentobarbital, and radiation treatment. The first three groups underwent cerebral implantations of a suspension of 9L gliosarcoma cells. Group 1 was left untreated and served as tumor-bearing controls. Group 2 received 30 Gy of whole-brain x-irradiation without anesthesia 8 days after tumor implantation. Group 3 received the same radiation treatment 15 minutes after pretreatment with 60 mg/kg of pentobarbital intraperitoneally. Groups 4 and 5 served as radiation controls, receiving 30 Gy of x-irradiation while awake and 30 Gy of x-irradiation after pentobarbital administration, respectively. Survival was calculated from the death of the last tumor-bearing rat. The mean survival time in tumor-bearing control rats was 20.8 +/- 2.6 days (+/- standard deviation). X-irradiation alone significantly enhanced the period of survival in rats implanted with the 9L tumor (29.7 +/- 5.6 days, p less than 0.03). Further significant prolongation of survival was seen with the addition of pentobarbital to the treatment regimen (39.9 +/- 13.5 days, p less than 0.01). Nontumor-bearing rats irradiated while awake (Group 4) survived 30.9 +/- 2.3 days. All of their pentobarbital-anesthetized counterparts in Group 5 survived. If pentobarbital had offered radioprotection to the tumor, then Group 3 would have had a shorter survival period than Group 2. This implies that the enhancement of survival time after irradiation results from selective protection of normal brain in this model. PMID- 2324800 TI - Persistent high lactate level as a sensitive MR spectroscopy indicator of completed infarction. AB - Serial proton (1H) and phosphorus-31 (31P) magnetic resonance (MR) spectroscopy of cerebral infarction was performed in rats to assess the sensitivity of these techniques for use in clinical cerebral infarction. In this experimental chronic infarction model, 31P spectroscopy tended to return to a "normal" pattern within 24 hours after induction of infarction in spite of pathologically proven completed infarction and, therefore, appeared not to be sensitive enough for clinical application. On the other hand, proton spectroscopy invariably showed persistent high lactate levels and was capable of distinguishing completed infarction from reperfused recovered brain. Persistent high lactate levels appear to be a good MR spectroscopic indicator of completed infarction. PMID- 2324801 TI - Evidence of the role of hemolysis in experimental cerebral vasospasm. AB - The short-term (less than or equal to 72-hour) reaction to subarachnoid injections of various blood components was determined in a canine model of cerebral vasospasm. Platelet-rich plasma (PRP) formed durable clots in the basal cistern surrounding the basilar artery and provoked no vascular reaction in 72 hours or more. Freshly isolated autologous erythrocytes resuspended in PRP likewise provoked no vasoconstriction in 72 hours although a second injection of fresh erythrocytes in PRP induced significant reaction, as in the conventional "double subarachnoid hemorrhage (SAH)" canine model. Hemolysate of fresh erythrocytes led to a severe immediate vascular reaction after introduction into the basal cistern using PRP as the carrier/clotting medium, as did the injection of intact erythrocytes incubated ex vivo for 72 hours. Resolution of the initial reaction was rapid for hemolysate, but slow and (depending on hematocrit) incomplete for intact "aged" erythrocytes. In vitro measurements of erythrocyte lysis in these media and histological examination indicate that the production of erythrocyte lysate was responsible for the vascular reaction observed, suggesting that the rate of lysis of erythrocytes in the subarachnoid clot is a major factor in the genesis of vasospasm after SAH. PMID- 2324802 TI - Radiosensitization of C6 glioma by thymidine and 41.8 degrees C hyperthermia. AB - The cytotoxic, antiproliferative, and radiosensitizing effects of thymidine (a nucleoside metabolite) were studied using the C6 glioma cell line in vitro. Radiosensitization by a combination of thymidine and 41.8 degrees C hyperthermia was also evaluated. Thymidine concentrations above 100 micrograms/ml completely inhibited C6 proliferation while concentrations of 100 to 1000 micrograms/ml (for up to 24 hours) decreased C6 cell survival to as little as 7.4% compared to untreated control cells. Radiosensitivity was enhanced by the administration of thymidine alone (400 micrograms/ml x 24 hours before irradiation); sensitization by 41.8 degrees C hyperthermia alone (1 hour ending immediately before irradiation) was less pronounced. Thymidine and hyperthermia together produced greater radiosensitization than did heat alone or thymidine alone. These data support the further investigation of thymidine as a neuro-oncology radiosensitizer. PMID- 2324803 TI - Vascular relaxation properties of calcitonin gene-related peptide and vasoactive intestinal polypeptide in subarachnoid hemorrhage. AB - The vascular relaxation effects of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) on the dog basilar artery after experimentally produced subarachnoid hemorrhage (SAH) were examined in vitro by an isometric tension recording method. Both CGRP and VIP induced dose-dependent relaxations in ring segments of the intact basilar artery of control dogs. The vasorelaxant action of CGRP was more potent than that of VIP. The single injection model of SAH was produced by injection of fresh autologous arterial blood (1 ml/kg body weight) into the cisterna magna on Day 0 of the post-SAH period, and the double-injection model was produced by two injections of blood (0.5 ml/kg each) on Days 0 and 2. Narrowing of the basilar arteries on vertebral angiograms was most prominent on Day 3 or 7 in the single- or double-injection model, respectively. Relaxation of the basilar artery induced by CGRP and VIP was to some extent decreased on Days 3 and 7 of the post-SAH period in the single injection model, and on Days 7 and 14 in the double-injection model. However, the vasorelaxant effects of CGRP and VIP were significantly enhanced on Day 14 of the post-SAH period in the single-injection model, and on Days 28 and 42 in the double-injection model. Subsequently, these effects returned to control levels by Days 28 or 63 in the single- or double-injection model, respectively. PMID- 2324804 TI - Multiple middle cerebral artery aneurysms in an infant. Case report. AB - An 11-month-old boy was admitted for evaluation of drowsiness, vomiting, and convulsions. Computerized tomography showed subarachnoid blood in the left sylvian fissure and a small intracerebral hematoma in the temporal lobe. Angiography revealed several aneurysms of the left middle cerebral artery (MCA). During surgery, 13 aneurysms were found arising from one main branch of the left MCA, and this segment of the MCA was trapped. Somatosensory evoked potentials did not show any change during surgery. The diseased arterial segment was examined histologically and the pathogenetic aspects of the case are discussed. Control angiography 6 months later excluded systemic disease or other aneurysms. The rarity of such lesions in childhood and their successful surgical treatment are discussed briefly. PMID- 2324805 TI - The abnormal pupil in Cheyne-Stokes respiration. Case report. AB - Cheyne-Stokes respiration commonly induces a rhythmic pupillary dilatation during hyperpnea and constriction during apnea. Failure of a pupil to dilate during hyperventilation indicates underlying sympathetic nerve paralysis. This report deals with an instance in which one pupil failed to constrict during apnea due to oculomotor nerve compression. The periodic respirations and anisocoria disappeared following surgical evacuation of a large ipsilateral subdural hematoma. PMID- 2324806 TI - Albendazole therapy for subarachnoid and ventricular cysticercosis. Case report. AB - Medical or surgical therapy for subarachnoid or ventricular cysticercosis is a controversial issue. The authors report a patient with cysticercus larvae in both ventricular and subarachnoid locations, who was successfully treated with albendazole. Thus, medical therapy has a role in the treatment of these forms of neurocysticercosis. PMID- 2324807 TI - Successful laboratory growth and analysis of CUSA-obtained medulloblastoma samples. Technical note. AB - The development of the Cavitron ultrasonic surgical aspirator (CUSA) has facilitated neurosurgical intervention for removal of central or peripheral nervous system tumors adjacent to or within vital structures. However, laboratory studies defining the phenotypic and genotypic properties of these tumors, both in cell culture and as xenografts in immunoincompetent animals, require viable tumor fragments free of microbial or red blood cell contamination. This report describes the use of a readily available sterile trap with the CUSA which, in conjunction with centrifugation and ammonium chloride lysis of the bloody aspirate, allowed collection of concentrated viable human medulloblastoma tumor cells. These cells were successfully established in cell culture and as transplantable xenografts in athymic mice. PMID- 2324808 TI - Oral complications of cancer therapies. PMID- 2324809 TI - Accuracy of ICP monitoring in posterior fossa lesions. PMID- 2324810 TI - Giant acoustic neurinomas. PMID- 2324811 TI - Uses for dural elevator. PMID- 2324812 TI - Multiple meningiomas. PMID- 2324813 TI - Bilateral proptosis from a subgaleal hematoma. PMID- 2324814 TI - Synaptic sprouting and nerve regeneration. PMID- 2324815 TI - BEIR V report. Experts urge cautious interpretation of higher risk estimates. PMID- 2324816 TI - Association between number and sites of new bone scan abnormalities and presence of skeletal metastases in patients with breast cancer. AB - Review of 1,441 bone scans performed on 242 breast cancer patients without known skeletal metastases identified 239 scans with new abnormalities. Findings on 54 of these 239 scans (23%) represented bone metastases. The proportion of scans reflecting metastases, grouped by the number of new abnormalities, was: (1) 20/182 (11%); (2) 9/26 (35%); (3) 4/9 (45%); (4) 1/2 (50%); greater than or equal to 5-20/20 (100%). When metastatic disease presented as a bone scan with 1-4 new abnormalities, the spine was the most common site of involvement (18 of 34 (53%)), followed by the skull (5/34; 15%), extremities and sternum (each 4/34; 12%). Rib lesions were the most common new findings on scans with less than 5 new abnormalities (seen on 76 of 219 scans (35%)) but only infrequently represented metastases (n = 2). Considering as indicative of malignancy only, those bone scans which demonstrated either (a) greater than or equal to 5 new abnormalities, (b) initial radiographic correlation suggestive of metastases, or (c) thoracic spine lesions with normal correlative radiographs, the presence of skeletal metastatic disease could be predicted with a sensitivity of 0.80 and a specificity of 0.94. PMID- 2324817 TI - Scintigraphic detection of bone and joint infections with indium-111-labeled nonspecific polyclonal human immunoglobulin G. AB - The utility of indium-111-(111In) labeled immunoglobulin G (IgG) to detect infection of bone and adjacent tissues was investigated. Proof of infection was obtained by cultures taken at surgery. All 32 patients showed focally increased uptake on the technetium-99m- (99mTc) methylene diphosphonate (MDP) skeletal scintigraphies. Labeled immunoglobulin correctly identified presence, location, extent and soft-tissue involvement of the suspected inflammatory site. In these patients, focally increasing accumulation was noted over 48 hr. Discrimination between infection and sterile inflammatory lesions was not possible. Two fractures, 6-mo-old, and an aseptic loosening of a total-hip prosthesis were not visualized. Side effects after the immunoglobulin administration were not observed. Radiolabeled immunoglobulin is a new and safe radiopharmaceutical for the investigation of infectious bone and joint disease. The sensitivity of this agent appears at least as high as that of labeled leukocytes. However, labeled immunoglobulin can easily be prepared in every nuclear medicine department. PMID- 2324818 TI - What is the best method for imaging focal infections? PMID- 2324819 TI - Extrahepatic uptake of technetium-99m-phytate: a prognostic index in patients with cirrhosis. AB - We examined the usefulness of technetium-99m-phytate (99mTc-phytate) hepatic scintigraphy in the evaluation of hepatic function, and the assessment of prognosis in patients with cirrhosis. Ninety-four patients with biopsy-documented cirrhosis had, at the time of entry into the study, a scintigraphy with 99mTc phytate complexed with calcium in vivo. Extrahepatic uptake (EHU) of 99mTc phytate on scintigraphy was graded from 0 (absent EHU) to 5 (important EHU) according to the relative distribution of the radiotracer between the liver, the spleen and the bone marrow. The severity of liver disease was also assessed according to the index of Child and Turcotte as modified by Pugh et al. Mean follow-up was 2 yr. EHU was correlated to the Pugh score (r = 0.73) and to survival. Survival at 2 yr was 97% for an EHU equal or inferior to 2.5, 62% for grades 3-4.5, and 31% for grade 5. In conclusion, hepatic imaging with 99mTc phytate, in addition to its diagnostic value, also contains valuable prognostic information in patients with cirrhosis. PMID- 2324820 TI - Left ventricular volume calculation using a count-based ratio method applied to multigated radionuclide angiography. AB - The purpose of this study was to investigate the accuracy of a new count proportional method for the measurement of left ventricular volume when applied to gated equilibrium blood-pool imaging. An equation is developed that relates total chamber volume, Vt, to the area of a pixel (M) and the ratio (R) of total counts within the chamber to the counts within the hottest pixel in the chamber such that Vt = 1.38 M3R3/2. The value of M is a constant for the particular scintillation camera-collimator system and R is obtained from observed count rates. All calculated volumes were compared to volumes measured using biplane contrast ventriculography. In 25 patients, the method for ventricular volumes gave an r of 0.95 and an s.e.e. of 23 ml [Volume (nuclear) = 0.94 Volume (cath) + 1.3]. Endsystolic volume was best calculated from end-diastolic volume and ejection fraction. Manual regions of interest were more accurate than automated regions of interest. This method appears to be as accurate as more complex approaches and has the advantage of not requiring attenuation correction or blood sampling. PMID- 2324821 TI - Simultaneous assessment of left ventricular wall motion and myocardial perfusion with technetium-99m-methoxy isobutyl isonitrile at stress and rest in patients with angina: comparison with thallium-201 SPECT. AB - The newly developed technetium-99m (99mTc) isonitriles can be used for the simultaneous evaluation of ventricular function and myocardial perfusion. We compared technetium-99m hexakis-2-methoxy isobutyl isonitrile [( 99mTc] MIBI) derived first-pass left ventricular wall motion at stress and rest with simultaneous myocardial perfusion defined by [99mTc]MIBI SPECT. These results were then compared with 201TI SPECT. We examined 28 patients with coronary artery disease; 25 had a previous myocardial infarction. We found concordance between segmental wall motion and myocardial perfusion imaging in defining normal, ischemic, and infarcted myocardium in 68% and 69% of segments using [99mTc]MIBI and 201TI respectively. The best agreement between wall motion and myocardial perfusion was seen in the inferior wall, while most of the discrepancies were found at the apex. Agreement between [99mTc]MIBI and 201TI SPECT myocardial perfusion was seen in 93% of segments. Technetium-99m-MIBI appears to be an ideal radiopharmaceutical for the simultaneous evaluation of ventricular function and myocardial perfusion during stress and at rest. PMID- 2324822 TI - Effect of metabolic inhibition on technetium-99m-MIBI kinetics in cultured chick myocardial cells. AB - Cellular uptake characteristics of hexakis(methoxyisobutylisonitrile)technetium(I) ([99mTc]MIBI), a myocardial perfusion imaging agent, were evaluated in cultured chick embryo heart cells. Myocyte net uptake of 99mTc-MIBI approached a plateau with a half-time of 9.3 +/- 1.5 min (mean +/- s.e.m.; n = 10). Tracer [99mTc]MIBI showed apparent competitive displacement by carrier [99Tc]MIBI at relatively high molar ratios ([99mTc]MIBI/[99Tc]MIBI) indicating a low affinity cellular retention process (apparent KD approximately 7 x 10(-5)). Metabolic inhibition induced by pre incubation of cells for 2.5 hr in rotenone (10 microM), iodoacetate (1 mM), or both metabolic inhibitors together reduced 1-min [99mTc] MIBI uptake to 74.1% +/- 8.0% (p less than 0.05), 6.2% +/- 3.4% (p less than 0.01), and 10.1% +/- 3.6% of control (p less than 0.01), respectively (n = 11-12). Half-maximal inhibitory concentration of iodoacetate was approximately 5 microM. Iodoacetate inhibition of [99mTc]MIBI uptake kinetics was time-dependent; no significant effect on [99mTc]MIBI uptake was seen during the first 60 min of metabolic inhibition despite significant depletion of ATP content determined on the same preparations (control ATP: 40.2 nmoles/mg protein versus iodoacetate incubation: 2.8 nmoles/mg protein; p less than 0.01). However, prolonged metabolic blockade did eventually depress 1-min [99mTc]MIBI uptake. These data indicate that a late component of myocardial cell injury can depress [99mTc]MIBI cellular uptake. PMID- 2324824 TI - Xenon-127m: a new radionuclide for applications in nuclear medicine. AB - Xenon-127m (127mXe) emits two gamma rays in cascade, with half-life of 69.2 +/- 0.9 sec. The first has the energy of 172.5 keV, and is emitted from the nucleus in 38% of the decays. The second gamma ray has the energy of 124.8 keV and is emitted from the nucleus in 69% of the disintegrations. Together they furnish 107 easily collimated gamma rays per 100 decays. Xenon-127m is generated readily by bombarding nearly saturated aqueous solutions of sodium or potassium iodide with 14-MeV protons. The 127mXe is swept out continuously, as it is produced, by bubbling helium upward through the solutions. Up to approximately 100 mci/l are obtained from the resulting mixture of gases. The 127mXe + helium is admixed with about five volumes of air (or oxygen) and then driven continuously to a scintillation camera located approximately 200 yd distant. When the mixture of gases is inhaled, high quality images of the lungs are obtained by means of an Anger scintillation camera. PMID- 2324823 TI - Yttrium-90-labeled monoclonal antibody for therapy: labeling by a new macrocyclic bifunctional chelating agent. AB - Yttrium-90 (90Y) is a promising radiometal for therapy of cancer due to its high energy beta emission and a physical half-life of 2.67 days. Bifunctional chelating agents based on DTPA cyclic anhydride or EDTA do not form Y(III) complexes that are stable under physiologic conditions. A new macrocyclic bifunctional chelating agent based on 1,4,7,10-tetraazacylododecane-N,N',N",N"' tetraacetic acid (DOTA) forms a stable Y(III) complex. It was converted to p bromoacetamidobenzyl-DOTA (BAD), and conjugated to monoclonal antibody Lym-1 via 2-iminothiolane, either as the free ligand or as the 88Y chelate. Stability studies of Lym-1-2IT-BAD-88Y in human serum in vitro showed no measurable loss of Y(III) from the ligand over a 25-day period. In Raji-tumored mice, tumor uptake was 16.8% of the injected dose per gram of tissue on Day 3. The bone uptake was 2.0, 3.6, and 2.1% injected dose per gram of tissue on Day 1, 3, and 5, respectively. The biodistribution of the control 88Y-citrate demonstrated continuous increase in bone uptake from 13.8% injected dose per gram on Day 1 to 24.9% injected dose per gram on Day 4. PMID- 2324825 TI - Attenuation correction in SPECT based on transmission studies and Monte Carlo simulations of build-up functions. AB - The quantitative information in SPECT images is distorted by photon attenuation and contribution of photons scattered in the object. It is, therefore, important to know the distribution of different attenuating tissues in order to be able to perform a proper attenuation correction. A correction method, based on correcting one pixel at a time by using density maps and build-up functions, has been developed. The density map has been produced by transmission measurements of the object using an external, solid 57Co flood source mounted on the scintillation camera head. The outline of the object is accurately defined by the map since the density values outside the object are very close to zero. The build-up of photons scattered in the object has been simulated by a Monte-Carlo code. SPECT-studies with 99mTc, 201T1 and 111In line sources in different parts of a non homogeneous Alderson phantom have been performed. The emission images have been corrected for photon attenuation using the measured density maps and the simulated build-up functions. The results show that quantitative measurements of the radioactivity in nonhomogeneous area can be accomplished to within +/- 10% for different radionuclides by using the attenuation correction described. PMID- 2324826 TI - Evaluation of a remote radioiodination system for radioimmunotherapy. AB - This report describes a remote radioiodination system which is inexpensive, easy to assemble, disposable, and capable of radioiodinating curie levels of activity safely. In addition to the safety afforded by this system, an immobilized oxidant and anion exchange resin are used to generate electrophilic iodine and remove free iodine, respectively. Reducing agents are not used and, therefore, when radioiodinating F(ab')2 fragments, degradation does not occur. In contrast, chloramine-T, sodium metabisulfite (CT/SMB) iodinations of F(ab')2 fragments resulted in products with up to 40% Fab' fragments. Radiolabeling yields (65.8% +/- 8.1%) and antibody immunoreactivity (68.8% +/- 8.0%) were not statistically different (p less than 0.001) from those obtained in remote CT/SMB iodinations. The system is currently being used to radioiodinate both IgG and F(ab')2 monoclonal antibodies with up to 450 mCi 131I for clinical radioimmunotherapy trials. PMID- 2324827 TI - Gallium-67-citrate imaging in the detection of focal lesions for anemia, proteinuria, and prolonged fever. PMID- 2324828 TI - Lymphoscintigraphy for cystic hygroma. AB - We present the case of an infant with a cystic hygroma investigated by lymphoscintigraphy. The source of lymph flowing into the hygroma was identified as were some ectatic lymphatics feeding it. Lymph flow was very rapid. The implications for therapy are discussed. Lymphoscintigraphy can assess many aspects of lymph flow not accessible by other means. PMID- 2324829 TI - Iodine-131 treatment of Graves' disease using modified early iodine-131 uptake measurements in therapy dose calculations. AB - We hypothesized that early uptake of iodine-131 (131I) at 3-6 hr (EU) by the thyroid could be used to calculate 131I therapy with results comparable to those obtained using late uptake of 131I at 20-28 hr (LU) results. A retrospective study was undertaken. Twenty-seven patients with untreated thyrotoxic Graves' disease were given 3-5 microCi of 131I and EU and LU were determined with an uptake probe. We derived a "best fit" curve on plots of EU (X-axis) and LU (Y axis). The equation for the curve (LU = -55.7 + 73.2 log EU) was used to predict late uptake (PU) from EU results on a second group of 24 similarly defined Graves' patients. PU and measured LU were then applied to 131I treatment calculations in these 24 patients. PU correlated closely with LU (r = 0.94). Dose calculations based on PU and LU gave very similar results (r = 0.97). Using this method, same day diagnosis and treatment of Graves' is achievable. PMID- 2324831 TI - Starport digital gamma camera. PMID- 2324832 TI - Statistical artifact in DPA measurements at low count rates. PMID- 2324833 TI - Dual-photon absorptiometry: depleted sources inappropriate in obese patients with narrow collimation. PMID- 2324830 TI - Diagnostic accuracy and pitfalls of [iodine-131]6-beta-iodomethyl-19 norcholesterol (NP-59) imaging. AB - NP-59 concentrates in steroid hormone synthesizing tissues, enabling scintigraphic localization and characterization of endocrine dysfunction in the adrenal cortex and ovary. Studying 108 consecutive cases from 1982 to 1985 and using clinical, biochemical, radiographic, and pathologic data, we performed a rigorous assessment of the accuracy and pitfalls of NP-59 scintigraphy. The evaluation was divided into categories of abnormal hormone secretion: Cushing's syndrome, primary aldosteronism, and hyperandrogenism. Additional categories included euadrenal tumors (without detectable hormone dysfunction) and sites of residual adrenal cortical tissue. The accuracy of NP-59 scintigraphy ranged from 71% in primary aldosteronism and 75% in euadrenal tumors, to 100% for Cushing's syndrome and hyperandrogenism. However, more than in most nuclear medicine studies, NP-59 imaging requires well-defined indications to be met for it to be efficacious, including the fulfillment of clear clinical, biochemical, and radiographic criteria. The high reproducibility of NP-59 scintigraphic interpretation was demonstrated when 40 random cases underwent interinstitutional exchange and through interobserver evaluation at the University of Michigan. Responses of 85/126 medical centers to questionnaires revealed the high level of NP-59 safety. PMID- 2324834 TI - Outcomes of research consortium project. AB - In previous articles, 1-3 the authors described the evolution and activities of the consortium project, a unique collaborative model for facilitating the conduct of nursing research in service settings. The authors' aim in these articles was to provide information useful to nursing administrators as they fulfill their professional obligation to support and foster the involvement of their staff in nursing research activities. Now, after five years of funding, the chronicle of this project's development, its successes, and difficulties would be incomplete without a final report of the experience. Therefore, this article describes the last two years of the consortium project. PMID- 2324835 TI - Transformational leadership and the nurse executive. AB - Effective nurse executive leadership is paramount in today's health care environment. Such leadership includes the qualities of a transformational leader and, to a lesser extent, a transactional leader. A study conducted among excellent nurse executives and members of their immediate staff showed that all executives were predominantly transformational leaders but also possessed transactional leadership skills. PMID- 2324836 TI - The influence of assumptions on effective decision-making. AB - In a competitive health care environment, the effectiveness of a nurse executive's decisions is enhanced by the use of a systemic set of assumptions. The author explains why this theory of decision-making is important, shows how three sets of assumptions manifest themselves in nursing administration practice, and presents a case study to show how nurse executives can use this theory to improve the effectiveness of their decisions. PMID- 2324837 TI - Dictated patient assessments. PMID- 2324838 TI - Rural nurses. Part I, Surviving cost containment. AB - Rural nurses from 13 small hospitals share their work lives and concerns. Five years of cost-containment have left them undaunted, but they worry about the financial viability of their hospitals. Their unique brand of nurse shortage has added an additional load that appears surmountable only through financial means, which have also disappeared through cost-containment. This is the story of "frontier nurses" and their fight to maintain an American institution. PMID- 2324839 TI - Impact of a restrictive work site smoking policy on smoking behavior, attitudes, and norms. AB - Three successive cross-sectional surveys were used to measure the impact of a restrictive smoking policy on employee smoking patterns, perceived exposure to environmental tobacco smoke, attitudes about the policy, and smoking-related norms in a large decentralized state agency. No significant change was detected in smoking prevalence, the proportion of smokers attempting to quit, or the total daily consumption of cigarettes by smokers. The daily consumption of cigarettes at work decreased significantly, from 16.9% to 4.9% smoking 15 or more cigarettes per day. The proportion of respondents bothered every day by coworkers' smoke dropped from 21.8% to 3.8%. Following policy implementation, the interaction between smokers and nonsmokers about smoking decreased. The findings suggest that restrictive work site smoking policies are effective at decreasing exposure to environmental tobacco smoke, but not, at least in the short run, at lowering smoking prevalence. Also, the decreased interaction regarding smoking may have the unintended consequence of reducing the perceived pressure on smokers to quit. PMID- 2324840 TI - Occupational outcome after military treatment for alcoholism. AB - Many studies measure the occupational outcome of alcoholism treatment utilizing reports from the patient and not from the employer. In an attempt to obtain an objective measure of occupational outcome, the authors used both supervisors' evaluations and clinical reports from aftercare personnel to observe 722 patients who completed a 6-week military inpatient alcoholism treatment program. Patients were observed for up to 2 years to determine prognostic indicators for post rehabilitation personal and occupational success. Continuous abstinence from alcohol was seen in 77% of the study group, whereas satisfactory posttreatment occupational performance was observed in 90% throughout the study period. Military rank, successful inpatient program completion, and aftercare program adherence were good predictors of long-term outcome, whereas extent of prior treatment for substance abuse and Michigan Alcoholism Screening Test scores were not. PMID- 2324841 TI - Methylene chloride exposure in furniture-stripping shops: ventilation and respirator use practices. AB - Four cases of serious methylene chloride (dichloromethane) poisoning, including fatalities, in small-scale furniture-stripping shops were reported to the Rocky Mountain Poison and Drug Center between 1984 and 1988. Adequate ventilation systems and use of recommended respirators may seem impractical or overly expensive to the operators of such shops. Twenty-one shops in the metropolitan Denver, Colorado area were surveyed. A half-facepiece respirator with organic vapor cartridges was worn at least part-time in 14 of 21 shops; none was worn in 7. In 10 of 21 shops, workers had experienced dizziness, headache, or nausea when stripping furniture. Current safety practices in small-scale furniture-stripping shops may be inadequate to keep methylene chloride exposure levels in compliance with latest recommendations, and serious or fatal overexposure can occur. PMID- 2324842 TI - Occupational phenoxyethanol neurotoxicity: a report of three cases. AB - 2-Phenoxyethanol, used as an anesthetic for handling small fish at a salmon hatchery, caused three women to experience headache and symptoms of intoxication during use, followed by diminished sensation and strength of hands and fingers, worse in the preferred hand. Persistent neuropathy did not develop in any of them. After 1 to 2 years of exposure, the women manifested gradual onset of symptoms of cognitive impairment with an inability to work. Neuropsychologic testing verified that all three had focal cognitive impairments that persisted. One also had documented labyrinthine hypofunction, which originated during this exposure. The immediate and delayed effects of 2-phenoxyethanol on the central nervous system resemble those of the other organic solvents. PMID- 2324843 TI - Reasons for participation and nonparticipation in a colorectal cancer screening program for a cohort of high risk polypropylene workers. AB - Little is known about reasons for participation in occupational colorectal cancer screening programs using flexible sigmoidoscopy and barium enema. To assess this issue, telephone interviews were conducted with a sample of participants and nonparticipants in such a program. This study was a follow-up of a previous assessment of factors that affected screening participation among a cohort found to have elevated rates of colorectal cancer. The major finding of this survey was that the absence of symptoms was the major reason for nonparticipation, although both participants and nonparticipants expressed the view that early detection was important and that colorectal cancer could be cured if treated at an early stage. Based on the results of this study and of other surveys, educational messages to workers explaining the asymptomatic development of colorectal cancer should be tried as a way of increasing participation. PMID- 2324844 TI - Ergonomic deficiencies: I. Pain at work. AB - This is Part I of a three-part series that examines various aspects of ergonomic deficiencies at work. This paper deals with pain at work and the association between such pain or discomfort and a poorly designed workplace or poorly structured job. Neglect of ergonomic principles brings inefficiency and pain to the workplace. An ergonomically deficient workplace may not cause immediate pain, because the human body has a great capacity for adapting to a poorly designed workplace or structured job. However, in time, the compounding effect of job and/or workplace deficiencies will surpass the body's coping mechanisms, causing the inevitable: physical symptoms, emotional stress, low productivity, and poor quality of work. PMID- 2324846 TI - Health insurance claims as morbidity data source. PMID- 2324847 TI - Occupational electromagnetic field exposure, solvent exposure, and leukemia. PMID- 2324845 TI - Fluoride, aluminum, and phosphate kinetics in cryolite workers. AB - Exposure to cryolite (Na3AlF6) dust may result in skeletal fluorosis. Eight male workers at a cryolite concentrator participated in a 4-day study after 5 days of vacation. Dust exposures were 0.16 to 21.2 mg/m3. Urine was collected before work began and during two 4-hour periods. Preshift urine fluoride concentrations increased during the week. Fluoride concentrations in postshift urine and serum both correlated with the dust exposures. Serum fluoride concentrations decreased with a half-life of 3.3 to 6.9 hours after work. Fluoride clearance was 40.5 to 76.5 mL/min at urinary flow rates of 0.89 to 2.21 mL/min. Serum aluminum concentrations varied without relation to the exposure, but the urinary aluminum excretion correlated with the fluoride levels. Preshift serum-phosphate concentrations increased significantly during the week, possibly indicating changes in mineral metabolism. For monitoring of individual uptake of cryolite dust, serum fluoride measurements are most useful. PMID- 2324848 TI - Impact of a facility-based corporate fitness program on the number of absences from work due to illness. AB - This study examined the relationship between participation in a facility-based fitness program and the number of reported absences from work due to illness. Employees who became members had a history of fewer absences before the program began in 1987 than employees who did not become members. Comparing 1988 with 1986, members experienced a significant decrease in absences, whereas nonmembers did not. Male and female members experienced 0.42 and 1.0 fewer days absent in 1988 than in 1986, respectively. Controlling for gender and previous absences, members could be expected to have 1.2 fewer absences in 1988 than nonmembers. On average, those who participated most frequently experienced the greatest improvement in attendance. A significant interaction between participation and 1986 absences indicated that a member's decrease in absences depended both on how many absences the member had to begin with, and how much he or she participated. Members having a high number of absences in 1986 could expect the greatest benefit from frequent participation. PMID- 2324849 TI - Magnetic resonance imaging of meniscal degeneration in asymptomatic knees. AB - Histopathological studies have suggested that spontaneous degeneration of knee menisci predisposes to symptomatic tears. We used magnetic resonance (MR) imaging to study noninvasively 20 patients with documented meniscal tears in one knee but asymptomatic contralateral knees, 18 normal controls, and 15 patients with symptomatic nonmeniscal knee disorders. A scoring system for MR signal changes was developed, and differences between the three groups were tested for significance by a multivariate analysis of covariance. MR signal changes in the menisci begin at around 30 years of age, progress with age, occur in both men and women, and occur in subjects who are inactive as well as those who undergo habitual knee stress exercises. Most subjects with documented meniscal tears in one knee have MR signals in the asymptomatic contralateral knee that reflect a more advanced degree of meniscal degeneration than in age-comparable normal controls or patients with nonmeniscal knee disorders. After adjustment for potential confounding variables, weight, and sex, the mean scores in the asymptomatic knee of patients with meniscal disease are significantly higher than those of normal controls (p = 0.021) and nonmeniscal disease patients (p = 0.019). These results document the occurrence of age-dependent degeneration within knee menisci, and support the hypothesis that a segment of the population has pre-existing meniscal degeneration predisposing them to traumatic or spontaneous meniscal tears. PMID- 2324851 TI - The potential of adult human perichondrium to form hyalin cartilage in vitro. AB - The usefulness of adult human perichondrium for the restoration of articular cartilage defects depends on the potential to form hyalin cartilage. In order to evaluate the capacity of adult human perichondrium to form hyalin cartilage in vitro, perichondrium of the rib of eight adult human beings was cultured in vitro. After removal of residual cartilage, perichondrial explants were cultured for 7 or 10 days. The explants were histologically examined using specific stains to prove the presence of glycosaminoglycans (GAGs) normal for hyalin cartilage. Clear differentiation of perichondrial cells towards chondrocytes was noted. The chondrocytes synthesized new matrix substances normally present in hyalin cartilage. This investigation supports the usefulness of adult human rib perichondrium for the restoration of cartilage defects. Due to the enormous potential of the rib perichondrium to form hyalin cartilage in vitro, even defects in joints with a rather thick cartilage layer might be restored using this biological material. PMID- 2324850 TI - Quantitation and relative distribution of extracellular matrix in Staphylococcus epidermidis biofilm. AB - The relationship between adherence of bacteria to foreign bodies and their deposition of extracellular matrix was examined on glass and suture material. To quantitate bacterial adherence, uptake of [3H]thymidine into bacterial DNA was analyzed. Corresponding amounts of extracellular matrix were measured by a new technique using [14C]glucose incorporation. This study shows that [14C]glucose preferentially labeled bacterial strains in proportion to biofilm production. The ratio of 3H14C in high biofilm producers was 0.9 and in low producers it was 3.7. Radioactive identification of organisms as high and low producers was confirmed by electron microscopy. The results presented here show that production and accumulation of biofilm over time is a stable characteristic in different strains of S. epidermidis. The use of ratios reflecting radiolabeling of bacteria and biofilm by [3H]thymidine and [14C]glucose, respectively, is a quantitative yet simple technique to assess extracellular matrix of different strains of S. epidermidis. PMID- 2324852 TI - Cathepsin B and cysteine protease inhibitors in human osteoarthritis. AB - The aim of this study was to determine the involvement of cathepsin B and its inhibitors in the proteolytic degradation of human osteoarthritic (OA) tissue. The characteristics of the cathepsin B found in both normal and OA cartilage and synovium were similar to those of the lysosomal cathepsin B. Two inhibitors of cysteine proteases were found with a molecular weight of 67,000 and 16,000 Da. The cartilage cathepsin B level of OA specimens (54.8 +/- 7.3 units/micrograms of DNA) was greater than the controls (39.8 +/- 3.2 units/micrograms of DNA). Mild moderate graded samples (78.1 +/- 12.0 units/micrograms of DNA) had significantly higher levels of enzyme activity than the severely graded ones (31.4 +/- 3.9 units/micrograms of DNA, p less than 0.001) and controls (p less than 0.01). Compared to controls (2.3 +/- 0.4 units/mg of tissue w.w.), cysteine protease inhibitory activity in OA cartilage was decreased in specimens with severe lesions (1.5 +/- 0.2 units/mg of tissue). This was particularly noted in patients who had not received steroid injections (1.2 +/- 0.3 units/mg of tissue, p less than 0.05). In OA synovia, the cathepsin B level was greater (40.7 +/- 7.4 units/mg of tissue w.w., p less than 0.02) than in the controls (13.6 +/- 3.7 units/mg of tissue). The cysteine protease inhibitory activity was similar in OA synovium (1.7 +/- 0.2 units/mg of tissue w.w.) and in controls (1.5 +/- 0.3 units/mg of tissue). This data demonstrated an imbalance between the levels of cathepsin B and cysteine protease inhibitors in OA tissue. A decrease of specific inhibitors could be an important contributing factor, particularly in more severe lesions. PMID- 2324853 TI - Effects of isolated rheumatoid synovial cells on cartilage degradation in vitro. AB - Rheumatoid synovium in coculture with cartilage has been shown to release a factor(s) that stimulates the depletion of glycosaminoglycans (GAG) from cartilage matrix. Human rheumatoid synovium was enzymatically disaggregated and the isolated cells were subjected to a variety of mechanical and immunological treatments. Synovial cell conditioned media (SCCM) were prepared and analyzed for their ability to stimulate GAG depletion. SCCM prepared from increasing concentrations of isolated synovial cells demonstrated cartilage degradative activity in a dose-dependent manner. This activity was characterized as interleukin-1 like and was found mostly within the adherent cell population where the synovial macrophages retained significant degradative ability. T cells alone were found to have no direct degradative effect on cartilage, but their presence appeared to augment the response of the adherent cells. The techniques described here provide a quantitative model for examining the degradative factors from synovium as well as the cellular interactions that promote their release. PMID- 2324854 TI - Effects of proteoglycan extraction on the tensile behavior of articular cartilage. AB - We undertook an interdisciplinary biomechanical and biochemical study to explore the extent and manner in which the total pool of proteoglycans influences the kinetic and static behavior of bovine articular cartilage in tension. Two biomechanical tests were used: (a) the viscoelastic creep test and (b) a slow constant-rate uniaxial tension test; and two enzymatic proteoglycan extraction procedures were used: (a) chondroitinase ABC treatment and (b) a sequential enzymatic treatment with chondroitinase ABC, trypsin, and Streptomyces hyaluronidase. We found that the viscoelastic creep response of all cartilage specimens may be divided into two distinct phases: an initial phase (less than 15 s), characterized by a rapid increase in strain following load application, and a late phase (15 s less than or equal to t less than 25,000 s), characterized by a more gradual increase in strain. A major finding of this study is that the kinetics of the creep response is greatly influenced by the glycosaminoglycan content of the tissue. For untreated and control specimens, the initial response comprises about 50% of the total strain, while for chondroitinase ABC and sequentially extracted specimens, the initial response comprises up to 83% of the total strain. Furthermore, most untreated and control specimens did not reach equilibrium within the 25,000 s test period, while enzymatically digested specimens often reached equilibrium in less than 100 s. Thus, we conclude that through their physical restraints on collagen, the bulk of proteoglycan present in the tissue acts to retard fibrillar reorganization and alignment under tensile loading, thereby effectively preventing sudden extension of the collagen network. In contrast, the results of our slow constant-rate uniaxial tension experiment show that essentially complete extraction of proteoglycan glycosaminoglycans does not affect the intrinsic tensile stiffness and strength of cartilage specimens or the collagen network in a significant manner. Hence, an important function of the bulk proteoglycans (i.e., the large aggregating type) in cartilage is to retard the rate of stretch and alignment when a tensile load is suddenly applied. This mechanism may be useful in protecting the cartilage collagen network during physiological situations, where sudden impact forces are imposed on a joint. PMID- 2324855 TI - Acidic fibroblast growth factor (aFGF) injection stimulates cartilage enlargement and inhibits cartilage gene expression in rat fracture healing. AB - The effect of the administration of acidic fibroblast growth factor (aFGF) on normal fracture healing was examined in a rat fracture model. One microgram of aFGF was injected into the fracture site between the first and the ninth day after fracture either every other day or every day. aFGF-injected calluses were significantly larger than control calluses, although this does not imply an increased mechanical strength of the callus. Histology showed a marked increase in the size of the cartilaginous soft callus. Total DNA and collagen content in the cartilaginous portion of the aFGF-injected calluses were greater than those of controls, although the collagen content/DNA content ratio was not different between the aFGF-injected and control calluses. Fracture calluses injected with aFGF remained larger than controls until 4 weeks after fracture. The enlarged cartilaginous portion of the aFGF-injected calluses seen at 10 days after fracture was replaced by trabecular bone at 3 and 4 weeks. Northern blot analysis of total cellular RNA extracted separately from the cartilaginous soft callus and the bony hard callus showed decreased expression of type II procollagen and proteoglycan core protein mRNA in the aFGF-injected calluses when compared with controls. A slight decrease in types I and III procollagen mRNA expression was also observed. We concluded that aFGF injections induced cartilage enlargement and decreased mRNA expression for type II procollagen and proteoglycan core protein. PMID- 2324856 TI - The three-dimensional tracking pattern of the human patella. AB - A study was undertaken to provide data on the three-dimensional tracking pattern of the patella, relative to the femur, in human knee-joint specimens. For this purpose, a highly accurate roentgen stereophotogrammetric analysis (RSA) method was applied. The three-dimensional motion patterns of the tibia and the patella were measured and represented in terms of three translations and three rotations each, during knee flexion in neutral (unloaded), endorotated, and exorotated pathways. We found that the patella displays complex but consistent three dimensional motion patterns during flexion, which include flexion rotation, medial rotation, wavering tilt, and a lateral shift relative to the femur. The motion patterns are very much affected by tibial rotations accompanying flexion. PMID- 2324857 TI - Measurement of lower extremity kinematics during level walking. AB - A simple external marker system and algorithms for computing lower extremity joint angle motion during level walking were developed and implemented on a computer-aided video motion analysis system (VICON). The concept of embedded axes and Euler rotation angles was used to define the three-dimensional joint angle motion based on a set of body surface markers. Gait analysis was performed on 40 normal young adults three times on three different test days at least 1 week apart using the marker system. Angular motion of the hip, knee, and ankle joints and of the pelvis were obtained throughout a gait cycle utilizing the three dimensional trajectories of markers. The effect of uncertainties in defining the embedded axis on joint angles was demonstrated using sensitivity analysis. The errors in the estimation of joint angle motion were quantified with respect to the degree of error in the construction of embedded axes. The limitations of the model and the marker system in evaluating pathologic gait are discussed. The relatively small number of body surface markers used in the system render it easy to implement for use in routine clinical gait evaluations. Additionally, data presented in this paper should be a useful reference for describing and comparing pathologic gait patterns. PMID- 2324858 TI - Bone blood flow after spinal paralysis in the rat. AB - The goal of this study was to investigate the acute and chronic effects of paralysis induced by spinal cord section or sciatic neurotomy on bone blood flow in the rat. Regional bone blood flow was measured in the early stage with the hydrogen washout technique and the change of whole bone blood flow was measured in the early and the late stages with the radioactive microsphere technique. Four to 6 h after cordotomy at the level of the 13th thoracic vertebra, the regional bone blood flow in the denervated tibia increased significantly (p less than 0.01). After hemicordotomy with rhizotomy at the same level, the regional bone blood flow in the denervated tibia increased significantly (p less than 0.05) 6 h postoperatively. The whole bone blood flow in the denervated tibia had also increased significantly (p less than 0.05) at 6 h and at 4 and 12 weeks postoperatively. After sciatic neurotomy, the regional and the whole bone blood flow in the paralytic tibia did not change significantly. The present study demonstrated that monoplegic paralysis caused an increase in bone blood flow in the denervated hind limb from a very early stage. It was suggested that the spinal nervous system contributed to the control of bone blood flow. PMID- 2324859 TI - The developmental morphology of a "periosteal" ligament insertion: growth and maturation of the tibial insertion of the rabbit medial collateral ligament. AB - The structural properties of ligament insertions change dramatically during growth and maturation, but little is known about their developmental anatomy. This study describes and quantifies changes in the gross and microscopic anatomy of the tibial insertion of the rabbit medial collateral ligament (MCL) during development and at skeletal maturity. Eighty animals were used for growth and descriptive studies. From this group, 27 animals, ranging in age from 1 to 24 months, were injected with fluorescent bone markers and their tibial insertions were processed undecalcified for histology. Sections were examined by polarized light and fluorescence microscopy to identify matrix and cells and to quantify mineral formation. Results showed that animals achieved histological skeletal maturity between 9 and 12 months of age. Body weights were a poor index of skeletal maturity. The tibial insertion was composed of five tissue layers, which changed proportions during growth and maturation. In immature animals, MCL fibers entered the periosteum; in older animals, MCL fibers were cemented to the tibia by advancing mineral. The tibial attachment of the MCL was thus transferred from the periosteum to the cortex during growth, suggesting that the term "periosteal insertion" is imprecise in adults. The hypothesis is put forward that these structural changes account for the reported increase in tensile failure of this insertion near skeletal maturity. PMID- 2324860 TI - The early effect of high molecular weight hyaluronan (hyaluronic acid) on anterior cruciate ligament healing: an experimental study in rabbits. AB - The purpose of this study was to assess, morphologically and biochemically, the effect of hyaluronan (HA) on the early repair process of the anterior cruciate ligament (ACL). Following partial bilateral laceration in the midsubstance of the cruciate ligament, a single dose of HA (MW of 3.6 x 10(6] was injected in one knee and saline in the contralateral knee. Postsurgery, the rabbits were allowed normal (nonimmobilized) cage activity, and were killed after 4 (n = 11) and 12 (n = 10) weeks. The ligaments were evaluated by gross morphology and graded according to the degree of repair. We used grades 1,2, and 3 for uncovered, partially covered, and totally covered lacerations, respectively. Five of the HA treated ligaments at each time studied were completely covered, compared to 0 at 4 weeks, and 1 at 12 weeks in the saline group. Paired evaluations of the lacerated ACLs showed that the HA-treated ligaments received a healing grade higher than the ligaments exposed to saline in 14 of the 21 animals. In the remaining animals, there was no difference between the sides. The repaired tissue of the ACLs was also examined by light and electron microscopy. When compared qualitatively with saline controls, HA-treated ligaments exhibited a more pronounced repair, with an increased angiogenesis and less inflammatory response. Biochemical analysis demonstrated a mean higher value of type III collagen in the HA-treated injured ACL than in saline-treated injured ACL (13.4 +/- 1.1% and 11.0 +/- 0.8%, respectively). This increased synthesis of type III collagen in the HA treated injured ACL was statistically higher (p less than 0.05) when compared to the saline-treated injured ACL. PMID- 2324861 TI - Dynamic stress response of the implant/cement interface: an axisymmetric analysis of a knee tibial component. AB - To determine the adverse effects on the implant/cement interface stresses caused by a dynamic load on the implant, an axisymmetric dynamic finite element analysis was performed for an idealized knee tibial component assuming perfect bonding at the interface. The component, consisting of a metal plate with a central stem, was subjected to a compressive load that varied with time as a terminated ramp function. At first, the reliability of the interface stress predictions was assessed by computing the effects of a number of method-related parameters, viz., the finite element mesh density, the assumed bone properties. Analysis was then performed considering the stem length, cement mantle thickness, and the type of implant metal as design variables. The analysis predicts high-frequency (600 Hz) stress oscillations of significant amplitude at those locations of the interface that are also subjected to high static stresses: near the stem-plate junction and the stem tip for normal stress, and at the stem tip for shear stress. However, the predicted stress amplitude has been found to be particularly sensitive to the assumed rise time of the input load function. With a rise time of 2.0 ms, an input condition considered to be severe enough to represent the most vigorous dynamic activity, the maximum stress augmentation, because of stress oscillations, is predicted to be less than 25%. In general, the design variables have been found to affect the static stresses much more than the dynamic ones. It has been concluded that for the cases studied, dynamic effects are relatively small and a static analysis is sufficient to characterize the interface stress condition. PMID- 2324862 TI - An investigation of a compliant interface for press-fit joint replacement. AB - Earlier in vitro studies showed that a compliant layer between a metal surface and trabecular bone improved the load distribution. In this study, the behavior of a compliant layer of Dacron velour was investigated in vivo using a patella resurfacing in a sheep as a model. Bilateral cases were used to compare the velour interface with a direct metal-to-bone interface. For the metal patellas, a fibrous layer developed adjacent to the metal while the underlying bone formed a new subchondral-like layer. With the velour interface, fibrous tissue invaded the velour, followed later by bone, which sometimes reached the metal surface. For follow-ups of 8 months or more, the load across the interface was transferred over localised patches, for both the press-fit and velour interfaces. There was no significant difference in the areas of contact. There was evidence that this was due to the irregularity of the bony surface beneath the fibrous layer, or to bone nodules actually growing up to the metal. It was concluded that in this in vivo model, the velour layer did not retain a more uniform load distribution compared with the press-fit joint, due to the nature of the bone and fibrous tissue that formed at the interfaces. PMID- 2324863 TI - A new "transducer-tipped" fiber optic catheter for measuring intramuscular pressures. AB - Laboratory and clinical tests were used to determine the efficacy of a new fiber optic "transducer-tipped" catheter for measuring intramuscular pressures. When pressures ranging from 0 to 250 mm Hg were applied by a mercury manometer, the fiber optic system accurately recorded the pressures. In addition, the fiber optic system showed long-term stability by accurately recording the manometer pressure over a 3 day period. The Slit system showed a higher magnitude of hydrostatic pressure artifacts with catheter tip movement as compared to the fiber optic system. The two catheters showed no difference when measuring pressures in pig muscle at rest or when being compressed throughout a range of 0 to 250 mm Hg. In human volunteers, both catheters measured essentially equal pressures at rest, during venous stasis, and during a combination of venous stasis and compression. For long-term assessment, the Slit system required as many as three saline flushes, whereas the fiber optic system measured pressures continuously without manipulation. We conclude that the fiber optic system is as accurate as the Slit catheter for measuring tissue fluid pressures at rest. In addition, the fiber optic system offers distinct advantages over conventional fluid-filled systems for measuring intramuscular pressures due to a lack of hydrostatic pressure artifacts caused by limb position and to the lack of flushing for long-term measurements. PMID- 2324864 TI - Abstinence versus nonabstinence: the objectives of alcoholism rehabilitation programs in Quebec. AB - Since the end of the nineteenth century, various attitudes toward alcoholism- from moralistic and legalistic to those rooted in medicine and psychology--have been adopted. Some of these have persisted and continue to influence the treatment programs available to alcoholics. One of the most popular explanatory models today is the traditional model, which prescribes abstinence as a treatment objective. However, more and more studies are showing that controlled drinking can be a viable alternative for many alcoholics. The aim of the present study is to determine the type of treatment goal preferred by alcoholism rehabilitation centers in the province of Quebec. As of March 31, 1987, the general directors of 78 of the 81 rehabilitation centers operating in Quebec were contacted and interviewed. The data most relevant to the present study came from the response to the following question: "Is a treatment goal other than complete abstinence acceptable for every client who registers in your program to resolve a problem of alcoholism?" The results indicate that most centers will not allow their clients to work toward any goal other than abstinence. PMID- 2324866 TI - Fluoxetine and bulimia. PMID- 2324865 TI - Correlates of persisting drug use among former youth multiple drug abuse patients. AB - This analysis is based on a follow-up study of 48 White male young adults who had been former youth multiple drug abuse patients in day-care treatment. For the most part, these respondents came from middle-class homes. As youthful offenders, many had been sent into treatment as an alternative to incarceration. Approximately six years after terminating their day-care treatments, interview data were collected when most were in their middle twenties. Consistent with previous research, those consuming more drugs were found to be more likely to have resisted treatment, to have trouble with the law, to have poorer work histories and diminished educational attainments, and they showed evidence of poorer psychological health. Surprisingly, the data also indicated that high volume drug users were more likely to be living in their parental homes, compared to those whose drug use patterns were more moderate. It is suggested that the pattern of taking up residence with one's parents while drug dependent may be encouraged by parental enabling. The implications of these findings for guiding efforts in substance abuse treatment are discussed. PMID- 2324867 TI - The disease model of addiction: a biopsychiatrist's view. PMID- 2324868 TI - The case for shorter residential alcohol and other drug abuse treatment adolescents. PMID- 2324869 TI - Twenty-five basic joining techniques in family therapy. PMID- 2324870 TI - Effect of zinc-deficient diet of varying duration on intestinal disaccharidase activity in the rat. AB - To determine whether zinc has a specific role on weight gain and intestinal disaccharidase activity, 42 male Sprague-Dawley rats were assigned to one of seven groups (n = 6 each). These were a baseline control group (0) that was killed to analyze initial intestinal disaccharidase (sucrase and maltase) activity, a second group (A) fed a zinc-deficient diet for 1 week, a third group (B) pair-fed control for A, a fourth group (C) fed a zinc-deficient diet for 2 weeks, a fifth group (D) pair-fed control for C, a sixth group (E) fed a zinc deficient diet for 3 weeks, and a seventh group (F) pair-fed control for E. All experimental groups received distilled deionized drinking water, whereas control groups received zinc-enriched (25 micrograms of zinc/ml) distilled deionized water. Water was given ad libitum. After killing, the mucosa of the proximal half of the small intestine was analyzed for protein and disaccharidase activity, and liver, kidney, and heart were analyzed for zinc concentration. Protein content and disaccharidase activity of the jejunal mucosa in the experiment and control groups did not differ significantly. However, animals on the zinc-deficient diet demonstrated mildly depressed growth rates that were proportional to the duration of the experiment, and significantly lower zinc concentration in the kidney in the experimental groups. The data indicate that administration of a zinc deficient diet for up to 3 weeks did not result in significant changes in intestinal mucosa protein content or in disaccharidase activity. PMID- 2324871 TI - A simple technique to feed newborn piglets. AB - We describe a simple and relatively inexpensive technique for feeding conventionally reared newborn pigs. The feeding system consists of a nipple assembly and an enteral feeding bag. Piglets are weaned at 4-10 h of age and are initially bottle-fed a simulated sow's milk formula. After adaptation to the synthetic nipple and artificial milk, the piglets are placed on the semiautomatic feeding system. Piglets fed in this manner gain weight at rates comparable to sow reared animals or animals fed via completely automated systems. PMID- 2324872 TI - Cow's-milk-induced erosive gastritis in an infant. AB - A 3 1/2-month-old male infant presented with hematemesis due to erosive gastritis following whole-cow's-milk feeding. The presence of eosinophilic gastritis, the disappearance of symptoms after withdrawal of whole-cow's-milk feeding, and the association with facial eczema suggest that gastritis was induced by cow's milk. Cow's-milk intolerance should be considered in the etiologic differential diagnosis of hematemesis and gastritis in infancy. PMID- 2324873 TI - Nontransmural myocardial infarction as a complication of untreated cystic fibrosis. AB - In a 2-year-old boy with untreated cystic fibrosis, an acute deterioration of his chronic respiratory insufficiency developed due to bilateral pneumonia. This condition caused acute right-sided heart failure and nontransmural myocardial infarction of the inferior wall. In concordance with this diagnosis, a marked increase of CPK-MB levels combined with transient severe ischemia on the ECG and the absence of myocardial injury at echocardiography was seen. At 3 years follow up, he was in good clinical condition. PMID- 2324874 TI - Differential effects of epidermal growth factor and hydrocortisone in human fetal colon. AB - The influence of epidermal growth factor (EGF) and hydrocortisone on the functional development of human fetal colon was studied in organ cultures. Fetal colon (14 to 17 weeks gestation) was cultured for 5 days at 37 degrees C in serum free Leibovitz L-15 medium alone or supplemented with 1, 10, and 100 ng of EGF/ml or with 50 ng of hydrocortisone/ml of culture medium. The overall morphology of the colonic explants was not altered by the hormonal addition. In the continuous presence of EGF (1, 10, and 100 ng/ml) for 5 days, a significant decrease of [3H]thymidine incorporation into DNA was observed. At the brush border level, the addition of EGF induced a significant drop in sucrase, maltase, and alkaline phosphatase activities. These enzymic modifications occurred between the third and fifth day of culture, whereas variation in DNA synthesis was already evident within 24 h. The addition of hydrocortisone at a dose affecting the small intestine (50 ng/ml) did not significantly influence colonic DNA synthesis nor the digestive enzymic activities. These observations show for the first time that EGF, but not hydrocortisone, influences the proliferation and differentiation of human fetal colonic mucosa. PMID- 2324875 TI - Hypocholesterolemic human milk. PMID- 2324876 TI - Microscopic colitis: a new cause of chronic diarrhea in children? AB - From a retrospective study on children who underwent colonoscopy or rectosigmoidoscopy with multiple level biopsies, we selected five patients whose rectocolonic endoscopic aspect was normal and contrasting with the presence of a microscopic colitis on biopsies. These five children had chronic diarrhea (mean duration of 14 months), associated with vomiting (three cases), abdominal pain (two cases), anorexia (two cases), abdominal distension (two cases), and weight loss (four cases). Symptomatic treatment was used in all children: loperamide (one case), trimebutine (three cases), and aluminium and magnesium silicate (two cases). One child received sulfasalazine for 2 months. After 1 year, all patients had normal stools. Rectosigmoidoscopy was performed in four patients and was normal. Biopsies obtained in three cases were normal in two cases and showed a persistent microscopic colitis in one case. Microscopic colitis may be a distinct cause of chronic diarrhea in children. PMID- 2324877 TI - Factors influencing the duration of acute diarrheal disease in infancy. AB - The majority of episodes of acute infectious diarrhea in infancy are of relatively short duration. Prolongation of the diarrhea presents problems in management, deterioration of the infant's nutritional status, and an increased mortality. As part of a prospective study of the etiology of acute infectious diarrhea, some factors associated with the probability (more or less) of having self-limiting disease have been identified. The well-nourished infant over 6 months of age is more likely to have self-limiting disease, whereas this outcome is least likely in the very young infant under 3 months of age, particularly if underweight for age. With the exception of Shigella, bacterial enteropathogens (Campylobacter fetus jejuni, Salmonella B, and certain enteropathogenic Escherichia coli types) were also associated with a decreased likelihood of self limiting disease. Rotavirus infection was associated with self-limiting disease except in the infant under 3 months of age, where the probability of self limiting disease was decreased. PMID- 2324878 TI - Feeding lactose-intolerant children with a powdered fermented milk. AB - Fresh yogurt has been proposed as a milk substitute for lactase-deficient patients. We investigated the possibility that a dried, low-fat milk fermented by yogurt microorganisms would be effective. Processing of a fermented milk by spray drying led to a powder with persistence of lactase activity (11.7 units/g) without storage at 4 degrees C and stable at room temperature (20-23 degrees C). The tolerance and absorption of 10.5 g of lactose in a volume of 150 ml was studied in 25 Gabonese lactase-deficient children aged 5-14 years in the form of a standard humanized milk formula followed 1 week later by the powdered fermented milk formula. Results of the breath hydrogen test showed that in 24 of 25 cases, lactose absorption was normal with a maximal rise of hydrogen over baseline of under 13 ppm after ingestion of the powdered fermented milk. The rise was above 20 ppm in the 25 children with the same load of lactose in the form of the standard formula and one-third had symptoms of lactose intolerance. This powdered fermented milk preparation should be considered as a valid approach in programs of nutritional support targeted to countries with a high prevalence of lactase deficiency. PMID- 2324879 TI - Neonatal serum protein levels as indicators of nutritional status: normal values and correlation with anthropometric data. AB - Twenty-one infants were studied to compare cord serum protein concentrations (SPCs) with samples drawn 3 days after birth. The results were compared with anthropometric measurements of the infants to determine the usefulness of serum studies in predicting the nutritional status of the newborn. SPCs of 19 serum protein subfractions were measured by laser nephelometry. In 17 of 19 proteins, the cord blood and newborn blood levels were highly correlated. C1Q and haptoglobin were the exceptions. The SPC was converted to serum protein mass (SPM) as follows: SPM = [(SPC) x (birth weight) x (0.85) x (1-hematocrit)]. Blood volume is approximately 0.85 dl of blood/kg of body weight and since these proteins are largely intravascular, it was postulated that the estimated total protein mass would be a more accurate index of nutritional state. Six proteins (C3, C4, prealbumin, retinol binding protein, transferrin, and albumin) were highly correlated with the anthropometry (arm circumference, skin fold thickness, length, weight, etc.). This study indicates that umbilical cord blood may be used to estimate a newborn's nutritional status. Transport proteins such as albumin, transferrin, retinol binding protein, and prealbumin are commonly used to assess adult nutritional status, and may be used in infants after estimating the total mass of the protein in the serum. PMID- 2324880 TI - The accuracy of test weighing for preterm infants. AB - A series of recent studies has suggested that preterm infants are capable of breast feeding at weights less than 1,500 g. However, estimating intake during breast feeding for these small infants is important for safe clinical practice and valid research. The purpose of this study was to compare the accuracy of test weighing as an estimate of intake for preterm infants using two types of scales: a mechanical scale (Toledo) commonly used in many special care nurseries, and a new electronic scale (SMART; Olympic Medical). Fifty clinically stable preterm infants, weighing between 1,088 and 2,440 g (mean = 1,599 g), who were clothed identically for all weights and feedings, were studied. Two experienced neonatal nurses (RN-1 and RN-2) collected the data. Before feeding, each infant was weighed once on each scale by each nurse; the order of nurse and scale was assigned randomly. Then, RN-1 administered a prescribed volume of feeding. After feeding, RN-2 weighed each infant twice on each scale; the order of scale was assigned randomly. RN-1 was blind to postfeed weights, and RN-2 was blind to actual volume of intake. Results indicated that differences between the actual and estimated volumes of intake were smaller for the electronic than for the mechanical scale on all measures. These findings suggest that test weighing with an electronic scale provides an accurate estimate of intake for preterm infants, and support the use of this instrument in clinical practice and research. PMID- 2324881 TI - Carnitine status and blood ammonium levels in low birth weight infants. AB - Forty-three low birth weight infants appropriate for gestational age (AGA) were monitored to evaluate carnitine status in relation to blood ammonium levels. The infants were grouped into three depending on blood ammonium level on postnatal day 7: 62.9 +/- 3.8 mumol/L in group 1 (N = 13), 38.9 +/- 8.4 mumol/L in group 2 (N = 23), and 24.5 +/- 2.9 mumol/L in group 3 (N = 9). Plasma free carnitine levels decreased in all three groups (p less than 0.001) and plasma short chain acylcarnitine increased only in group 1 (p less than 0.002), compared to findings in normal infants. The blood ammonium level positively and negatively correlated to plasma short chain acylcarnitine (p less than 0.002) and plasma free carnitine levels (p less than 0.002), respectively. The reabsorption rate of free carnitine in renal tubules (RRFC) was decreased at rates of 37.5, 27.5, and 25% of infants in groups 1, 2, and 3, respectively. The acylcarnitine/free carnitine clearance ratio (RAFCC) was decreased in groups 1 (p less than 0.01) and 2 (p less than 0.05) compared with group 3. Thus, an accumulation of short chain acyl moieties and insufficiency in renal absorption of free carnitine are putative causes of lowered plasma free carnitine in infants with higher blood levels of ammonium. The possibility that the carnitine status regulates blood ammonium levels in low birth weight infants warrants continued investigation. PMID- 2324882 TI - Hepatic hypervitaminosis A: a familial observation. AB - Four siblings with hepatic fibrosis are described. The liver damage in these patients was secondary to chronic ingestion of massive doses of vitamin A for congenital ichthyosis. Although the extrahepatic manifestations were helpful in the diagnosis of hypervitaminosis A, the distinctive features of hepatic histopathology were confirmatory. The plasma concentrations of vitamin A and retinol-binding protein were misleading. The recovery from the liver damage in these patients was slow despite a complete withdrawal of the vitamin A intake. These cases show the importance of hepatic vitamin A assessment in the diagnosis of hepatic fibrosis. PMID- 2324883 TI - Treatment of Wilson's disease with triethylene tetramine hydrochloride (Trientine). AB - Penicillamine is the drug of choice for the treatment of Wilson's disease, whatever the stage of the illness. Toxic manifestations may preclude the use of this life-saving drug in some patients and discontinuation of penicillamine therapy usually leads to death. We report our experience with Trientine in seven patients, aged 13 to 33 years, with Wilson's disease who developed toxic manifestations with penicillamine that required discontinuation of therapy. These include two with nephrosis, one with neutropenia, two with thrombocytopenia, and one each with a SLE-like and a Henoch-Schonlein-like syndrome. The patients were treated for periods from 6 weeks to 16 years with a dose of 0.5 to 2 g/day. Trientine proved to be an effective alternative copper chelating agent in the treatment of Wilson's disease in patients with penicillamine-induced neutropenia, thrombocytopenia, SLE, and nephrosis. No serious untoward side effects were noted. PMID- 2324884 TI - Epidemiology of neonatal jaundice in the Jerusalem population. AB - Of 10,122 singleton babies born from January 1, 1984 to March 31, 1988, we compared 1,154 term infants with high serum bilirubin levels (greater than 12.9 mg/dl) to 1,154 infants with low serum bilirubin levels (less than or equal to 12.9 mg/dl) randomly selected from the remaining 8,968 subjects. We found that a high bilirubin level was significantly associated with male sex; maternal diabetes (chronic and gestational); pregnancy-induced hypertension; previous sibling with neonatal jaundice; delivery by cesarean section, vacuum, or forceps; epidural anesthesia; mother with blood type O; first delivery; cephalohematoma; short gestation; lower birth weight; and lower birth order (p less than 0.01); and older maternal age, low percentile for birth weight, and the percentage of weight loss during hospitalization (p less than 0.05). Variables with significantly different frequencies in control and study groups were used in a multivariate analysis, thus further refining the data by the use of logistic regression. Teenage mothers (less than or equal to 19 years old) had the lowest risk, whereas older mothers (greater than 35 years old) had the highest risk of all age groups for having an infant with neonatal jaundice. First delivery and previous sibling with neonatal jaundice were also risk factors. Male sex, short gestation, and delivery by vacuum extraction were other notable risk factors. Our results suggest that, even among industrialized Western societies, risk factors may interact differently to produce higher neonatal serum bilirubin levels. The importance of a risk factor may also be dependent upon its relative prevalence in a parturient population. PMID- 2324886 TI - Dominant dorsal duct syndrome: pancreas divisum redefined. PMID- 2324885 TI - Physicochemical characterization and biological activity of intrinsic factor in cystic fibrosis. AB - Absorption of crystalline labeled cobalamin is strongly decreased in cases of cystic fibrosis. In order to determine if this is due to an alteration or a lack of activation of intrinsic factor by proteases, the physicochemical properties and biological activity of intrinsic factor have been studied. Intrinsic factor was purified 800-fold from stimulated gastric juice of cystic fibrosis patients with a yield of 64.2%. Cystic fibrosis intrinsic factor had an estimated Mr of 57,000 in SDS-polyacrylamide gel electrophoresis. Its carbohydrate content resembled that of normal human intrinsic factor, except that the ratio fucose/sialic acid was higher (6.1 and 1.6, respectively) and that the content in N-acetylgalactosamine was decreased. The same alterations in carbohydrate composition were observed for Hc purified from cystic fibrosis saliva. Purified intrinsic factor from cystic fibrosis gastric juice was biologically active in vitro in the presence of ileal solubilized receptor as well as in vivo (Schilling test). The fate of iodinated cystic fibrosis intrinsic factor in guinea pig ileum studied by high-resolution radioautography was similar to that of normal intrinsic factor. In conclusion, despite modifications of the carbohydrate content of the molecule, the biological activity of intrinsic factor is not altered in cases of cystic fibrosis. The malassimilation of crystalline cobalamin observed in cystic fibrosis is due to a mechanism independent from intrinsic factor secretion. PMID- 2324887 TI - Intestinal permeability tests: are they clinically useful? PMID- 2324888 TI - Phenobarbital can aggravate a cholestatic bile acid pattern in infants with obstructive cholangiopathy. AB - The effect of phenobarbital on urinary bile acid excretion in intrahepatic cholestasis was studied in four boys 4-43 months of age who received 10 mg/kg of body weight of phenobarbital for a period of 3 weeks-3 years. One child was observed at two different periods: with and without histologically proven cirrhosis. Before the treatment period, the infants excreted 10-fold higher amounts of bile acids in urine than healthy children. The primary bile acids predominated, and there were also increased amounts of polyhydroxylated bile acids, 3 beta-hydroxy-5-cholenoic acid, and ketonic bile acids but small amounts of secondary bile acids. After the phenobarbital treatment, the patients further increased their urinary bile acid excretion, including all kinds of bile acids except the secondary ones. The sulfated fraction did not increase in absolute amounts, and its relative percentage decreased from a mean of 60-33%. Liver function test results generally did not improve, although serum concentration of bilirubin decreased. Most of these changes suggested a worsening of the cholestatic state after phenobarbital treatment. The results indicate that at our present state of knowledge, phenobarbital should not be given routinely to infants or children with intrahepatic cholestasis. PMID- 2324889 TI - Prostaglandin and fatty acid metabolism in patients with extrahepatic biliary atresia. AB - The relationship between essential fatty acid (EFA) deficiency and disturbance of prostaglandin (PG) biosynthesis was studied in children after radical operation for extrahepatic biliary atresia (EBA). In addition, to investigate the method for treatment of postoperative EFA deficiency and disturbance of PG biosynthesis, the serum fatty acid and plasma PG levels were determined before and after supplementation of an EFA-rich powder (38 g of linoleic acid per 100 g of powder) through Suruga II enterostomy. Before administration of the EFA-rich powder, linoleic acid, arachidonic acid, PGE1, and PGF2 alpha levels were significantly lower in both good bile excretion and poor bile excretion groups than in the control group. After administration, linoleic acid and PGE1 levels significantly increased in the good bile excretion group as compared with the preadministration values. These results suggest that the supplementation of EFA-rich powder is an effective treatment for linoleic acid deficiency and disturbance of PGE1 biosynthesis in postoperative EBA patients. PMID- 2324890 TI - Modulation by human milk of IgG subclass response to hepatitis B vaccine in infants. AB - The influence of breast and formula feeding on specific anti-hepatitis B surface antigen (HBsAg) IgG subclass production and distribution has been investigated in 40 healthy infants, born to HBsAg-positive mothers and vaccinated against hepatitis B virus (HBV). Twenty children were bottle fed and 20 were breast fed. Specific subclasses were detected at the 4th and 12th months using an enzyme linked immunosorbent assay with monoclonal antibodies. A defect in total IgG and IgG subclasses was previously excluded. Significant differences were observed both at the 4th and 12th months for IgG1 and IgG2. Breast-fed infants had significantly higher levels of specific IgG2 (about three times higher), while IgG1 levels were significantly higher in formula-fed infants. Anti-HBsAg IgG4 levels were always higher in bottle-fed infants, but a statistical significance was never present. No difference was found in specific IgG3 levels. This study reports the evidence that breast feeding influences specific IgG subclass synthesis against a viral antigen and suggests an immunologic modulation of the response to vaccines dependent not only on age but also on factors present in human milk. PMID- 2324891 TI - Esophageal reflux in symptomatic and asymptomatic infants: postprandial and circadian variations. AB - Twenty-two full-term infants, nine asymptomatic and 13 symptomatic for chronic digestive problems, had long-term (mean = 21 h) esophageal pH monitoring. All children were observed in strictly standardized conditions including meals and body position. Symptomatic infants presented significantly more esophageal refluxes, spent a greater percentage of time with a pH below 4, had a longer reflux duration (longer clearing time) and presented more refluxes lasting more than 5 min. We performed a determination of the circadian variations of parameters associated with esophageal reflux. Asymptomatic and symptomatic infants presented significant circadian variations of the percentage of time below pH 4 and of the longest duration of reflux. However, symptomatic infants had significantly higher mean values and increased amplitudes of circadian rhythms. Moderate phase lag existed for certain variables between symptomatic and asymptomatic infants. These findings can be helpful when interpreting the results of long-term esophageal pH monitoring. PMID- 2324892 TI - Do esophageal pH monitoring data depend on recording equipment and probes? AB - Esophageal pH monitoring data are influenced by numerous patient- and/or technical equipment-related factors. In this study, data obtained with 10 pH recording devices of two different companies and 10 pH glass-microelectrodes with an external reference electrode of one company, calibrated by different persons, were compared. Pearson correlation coefficients regarding the reflux index (the percentage of the investigation time with a pH less than 4) ranged from 0.93 to 1.00. The lowest correlation coefficient (0.73) was obtained by comparing the number of episodes with a pH less than 4 recorded with devices from different companies. These results suggest that differences in pH monitoring data recorded in comparable conditions with one type of pH electrode are irrelevant as far as clinical routine investigations are concerned. Data are not significantly influenced by the recording devices themselves, the age of the electrodes, or the skin-potential differences induced by the person calibrating the probes. PMID- 2324893 TI - Duodenogastric reflux in children: measurement of phospholipids and trypsin in gastric content. AB - The duodenogastric reflux (DGR) is a suspected cause in some esogastric pathologies in adults: esophagitis, peptic gastric ulcers, stress ulcers, ulcers secondary to drugs, gastric cancer, and gastritis. The toxic substances of the reflux are essentially bile acids, lysolecithin, and trypsin. A number of diagnostic methods have been proposed in the adult. This study suggests a diagnosis technique for DGR in the child. Fasting gastric juice was collected by gastric intubation during 1 h and three substances were measured: phospholipids as markers of biliary reflux, trypsin as a marker of pancreatic reflux, and sialic acid as a marker of the degradation of gastric mucus. The sialic acid enabled us to evaluate some of the toxicity of DGR on the stomach. The study of 49 child subjects permitted us to show the existence, in the normal child, of biliopancreatic markers in the stomach under fasting conditions through a physiological DGR; to define the norms in the child, varying according to three age groups: 0-2 months, 2-12 months, and 1-4 years (the maximum values for an age above 4 years seemed to correspond to those in the adult); and to suggest the existence of a pathological DGR in children with antral gastritis or ulcers. PMID- 2324894 TI - Efficacy and safety of a diazepam and meperidine combination for pediatric gastrointestinal procedures. AB - Little has been published about outpatient sedation for pediatric patients. We designed a study to evaluate the efficacy and adverse effects of diazepam and meperidine in combination for sedation in ambulatory pediatric patients undergoing endoscopy, colonoscopy, or liver biopsy. Thirty patients (7 months-20 years) were observed. Each patient received a single combined dose of intravenous diazepam and meperidine. The standard dose was 0.1 mg/kg for diazepam and 2.0 mg/kg for meperidine. In patients weighing greater than 100 lb, set doses of meperidine (100 mg) and diazepam (5 mg) were used. The time to achieve sedation and the vital signs were measured; cooperation, emotional state, and drowsiness were rated before, during, and after procedures. The amnesic effect was noted, as were any adverse effects. Diazepam and meperidine were effective in 26 of 30 patients, with sedation generally produced within 2-3 min. Cooperation and emotional state improved significantly following drug administration (p less than 0.05). When a prospective 24-h telephone follow-up study was instituted in 40 consecutive patients receiving diazepam and meperidine no significant adverse effects were noted. Only 20% of patients old enough to be questioned remembered the procedure. Diazepam and meperidine in combination appear to be effective and safe in pediatric patients undergoing gastrointestinal procedures. Prolonged monitoring of patients does not appear necessary in this patient population. PMID- 2324895 TI - The nutritional value of oat flour for very young children. AB - Whole groat flour was consumed by nine infants and young children as 22.5, 45, or 67% of total diet energy (one half of 6.4%, all of 6.4%, or all of 9.6% protein energy). Isonitrogenous and isoenergetic casein control diets were given. Apparent absorption of oat nitrogen (N) was consistently around 75% of intake (casein, 87%), but absorptions of oat energy, carbohydrate, and fat, as percentages of intake, decreased disproportionately as oat flour intake was doubled and then tripled. Apparent retentions were 39 +/- 5% of mixed oat-casein protein intake in the 22.5% diet, the preceding and following casein controls being 38 +/- 8% (NS) and 44.4% (p less than 0.05) of the intakes; 32 +/- 6% from oats in the 45% diet, controls 38 +/- 5 and 46 +/- 5% (both p less than 0.05), and 33 +/- 11% from oats in the 67% diet, controls, 36 +/- 9% (NS). Fasting plasma free total essential amino acid (TEAA) levels of children consuming 45% oats were low (562 +/- 119 mumol of TEAA/L) and did not change significantly after meals. Fasting molar proportions of individual essentials (millimoles of EAA per mole of TEAA) were similar to those from milk protein diets and did not vary significantly 3 and 4 h after feeding, suggesting that no individual amino acid, but rather protein digestibility, was first limiting to N retention. Oats are a satisfactory source of energy, protein, and fat for very young children and many infants. PMID- 2324896 TI - Routine L-ascorbic acid supplementation does not alter iron, copper, and zinc balance in low-birth-weight infants fed a cows'-milk formula. AB - The effect of ascorbic acid (AA) [284 mumol (50 mg) twice daily] on the net intestinal absorption and maximum apparent retention of Fe, Cu, and Zn was investigated by metabolic balance studies in a randomised crossover study of six low-birth-weight (LBW) neonates fed a cows'-milk-based formula containing (mumol/L) Fe, 126; Cu, 11; Zn, 87; and AA, 400. Absorption +/- SD (Fe, -5.0 +/- 7.5; Cu, 0 +/- 0.4; Zn, -0.8 +/- 3.4) (mumol kg-1 day-1) was not altered by AA (Fe, -4.1 +/- 4.6; Cu, 0.3 +/- 0.6; Zn, -1.1 +/- 2.7) neither was retention (without AA: Fe, -6.0 +/- 8.4; Cu, -0.1 +/- 0.3; Zn, -2.4 +/- 4.2; with AA: Fe, 4.9 +/- 4.7; Cu, 0.1 +/- 0.6; and Zn, -2.7 +/- 3.1). Supplements of AA administered as in the circumstances of routine care of LBW neonates do not enhance the absorption and retention of Fe, nor do they impair these aspects of the metabolism of Cu and Zn. PMID- 2324897 TI - Rapid endoscopy room diagnosis of Campylobacter pylori-associated gastritis in children. AB - A modified urease broth test was used in 109 gastric biopsy specimens of children that yielded a 96% sensitivity and a 100% specificity rate for Campylobacter pylori infection. The longest reaction time was less than or equal to 4 min. The correlation between the degree of C. pylori infection and the reaction time was found to be highly significant (gamma = 0.78, p less than 0.001). Patients were examined as outpatients, and immediate medications were prescribed for eradication of the bacteria on the basis of the urease broth test results. This is the first report on the use of this modified rapid urease test for the diagnosis of C. pylori infection in children. PMID- 2324898 TI - An in vitro model to study aspects of the pathophysiology of murine rotavirus induced diarrhoea. AB - An in vitro system is described and validated for studying transport of solutes and water in both uninfected and rotavirus-infected neonatal mouse intestine. Control intestine exhibited stable water absorption for periods of up to 40 min. Water absorption was temperature-dependent. Na-dependent, and enhanced by glucose containing perfusion solutions. Theophylline induced net secretion of water by control intestinal tissue. Water transport by rotavirus-infected lower small intestine was significantly depressed as compared to control levels, and rotavirus-infected middle small intestine exhibited net secretion of water. Upper small intestine and colon from infected animals did not differ significantly from control tissues in their ability to transport water. Water secretion by infected middle small intestine was reversed to absorption by glucose-containing solutions. PMID- 2324899 TI - Plasma amino acids in long-term models for obstructive versus toxic liver injury in developing rats. AB - We evaluated plasma amino acid (AA) concentrations associated with a histologically defined lesion caused by bile duct ligation (BDL) in developing rats. Nineteen rats that underwent BDL at 14 days of age had marked bile duct proliferation with bridging fibrosis, multifocal lobular necrosis, and minimal polymorphonuclear periportal infiltrate in their livers at sacrifice (11-31 days after ligation). These were compared to two age-matched control groups: 21 nonoperated rats and 22 sham-operated rats; and eight rats with cirrhosis caused by carbon tetrachloride. Signs of liver damage including jaundice, growth failure, bleeding, and ascites were accompanied by elevated bilirubin, ammonia, aspartate aminotransferase (AST), and alkaline phosphatase levels in BDL rats compared to controls. They had higher concentrations of total AAs, phenylalanine, tyrosine, and cyst(c)ine when compared to controls and to CCl4-treated rats. Micronodular cirrhosis was present in CCL4-treated rats with elevated AST and alkaline phosphatase levels. Glutamine and glutamate levels were higher in them than in BDL rats or controls, and branched chain AA levels were lower. These two chronic lesions, one obstructive and one hepatotoxic, both result in fibrotic change, but their metabolic abnormalities as reflected in plasma AA levels are distinct. We found that BDL is an appropriate model with which to study metabolic changes and growth failure due to chronic biliary stasis during its progression to frank cirrhosis. PMID- 2324900 TI - Manometric variations following spiral myotomy for long-gap esophageal atresia. AB - We have previously demonstrated that a spiral myotomy and delayed definitive procedure is a viable alternative for esophageal reconstruction in long-gap esophageal atresia. In this study we sought to determine whether this procedure leads to esophageal motility disturbances and to compare the manometric findings with controls as well as with those seen in children with esophageal atresia and primary anastomosis. Six beagles had esophageal transection and a spiral myotomy, one had esophageal transection without a myotomy, and two served as normal controls. Following esophageal reconstruction, esophageal manometry was studied in all dogs using a standard pull-through technique. We found that the three control dogs all had similar manometric findings with normal peristalsis. In contrast, the dogs with a spiral myotomy all had propagation of waves in the myotomized segment but termination of waves at the anastomotic site. There was delayed velocity through the myotomized segment and retrograde peristalsis distally. Finally, upper esophageal sphincter pressure was elevated, while lower esophageal sphincter pressure was similar to that in the normal dogs. These findings are similar to those described in children with primary anastomosis and suggest that (a) spinal myotomy is a good alternative to other esophageal replacement options in patients with long-gap esophageal atresia and that (b) the motility dysfunction observed in children with esophageal atresia following primary anastomosis may be secondary to the disruption of the vagus nerve and that may be part of the congenital abnormality or secondary to surgical trauma. PMID- 2324901 TI - Treatment of duodenocutaneous fistula with somatostatin analog in a child with dermatomyositis. AB - A 6-year-old girl with juvenile dermatomyositis complicated by five duodenal perforations is described. The treatment consisted of suture closure of the perforations, reinforcement of the suture line with an omental graft, and adequate drainage of the closure site. The use of a somatostatin analog was successful in promptly arresting a leak from the duodenal perforations that had persisted for 3 months after the operation despite prolonged bowel rest and total parenteral nutrition. On follow-up observation 2 months later, the patient had no abdominal complaints and was tolerating oral intake without problems. PMID- 2324902 TI - Episodic vomiting due to intermittent duodenal intussusception. AB - Cyclic vomiting is a psychosomatic syndrome, but it is also a diagnosis of exclusion. Before such a diagnosis can be made, an organic basis for the episodes of vomiting must be ruled out. We describe a case of episodic vomiting in a school-aged girl. Endoscopic examination eventually confirmed a diagnosis of intermittent duodenal intussusception due to an enteric duplication. Removal of the duplication abolished the episodes of vomiting. The differential diagnosis of episodic vomiting is discussed, and the literature on intussusception is reviewed. Endoscopy should be considered in a child with a history of episodic vomiting. PMID- 2324904 TI - The sweat crystallization test in the diagnosis of cystic fibrosis. PMID- 2324903 TI - Necrotizing perianal infection in children: report of two cases. AB - Two girls aged 1 9/12 years and 5 months were treated for necrotizing perianal infection. In both patients, the necrotizing ulcers around the anus developed following an episode of diarrhea. A poor nutritional status with low body weight (25th percentile) and hypoalbuminemia (2.5 g/L) in the elder patient, as well as a hypogammaglobulinemia in the younger one, may predispose them to bacterial infection and subsequent perianal lesions. Anorectal trauma was denied. The necrotizing infection was confined to the skin and the subcutaneous tissue layer, and both patients had a benign clinical course. We report it and briefly discuss the etiology and treatment of this rare disorder. PMID- 2324905 TI - Sex differences in cognitive processing in children treated with CNS prophylaxis for acute lymphoblastic leukemia. AB - Evaluated cognitive processing in 51 children (27 female, 24 male) who had been treated for acute lymphoblastic leukemia (ALL) with CNS prophylaxis (cranial radiation in combination with intrathecal chemotherapy) and were continuously disease-free for 5 to 12 years. The control group comprised 15 children treated for Wilm's tumor. Functions assessed included visuoperceptual skills, generation of organizational strategies, sensitivity to organizational structure, and attention. The ALL group showed performance deficits relative to the solid tumor controls in appreciating the organization inherent in complex visuospatial material and alertness, with females more severely affected than males. Sex differences favoring males on IQ and academic achievement were related to these cognitive processes. PMID- 2324906 TI - Effect of elaboration on the acquisition and maintenance of cardiopulmonary resuscitation. AB - Investigated the influence of training on the acquisition and retention of cardiopulmonary resuscitation (CPR) skills by 38 sixth-grade children. Three training methods were compared: precise elaboration, imprecise elaboration, and maintenance rehearsal. Each of these methods was coupled with behavioral training and compared to a no-treatment control condition. Three CPR situations were selected for training: breath and pulse present, breath absent/pulse present, and breath and pulse absent. Data were collected at pretest, posttest, and 1-, 3-, and 5-month follow-ups, the dependent variable responses occurring in sequence. Results indicated that children in the three treatment conditions acquired and maintained the CPR responses at a significantly higher level than the control group. Evidence for the potential superiority of the precise elaboration group over the other conditions was provided. PMID- 2324907 TI - Children's coping with diabetes: understanding the role of cognitive development. AB - Asked diabetic children at two levels of cognitive maturity to describe their efforts to cope with diabetes-related stress. Results revealed certain developmental trends. Relative to more cognitively mature youngsters, the coping styles of preformal operational children showed greater emphasis on primary control coping (trying to directly change stressful conditions). Secondary control coping (trying to adjust to circumstances as they are) increased with cognitive maturity, however, overall, primary control and instrumental coping strategies appeared salient for both groups of youngsters. The nature of these developmental trends and their implications for children's disease-related adjustment are discussed. PMID- 2324908 TI - Behavior problems in children with the presenting problem of poor school performance. AB - Used 3 methods of assessing behavioral disturbance in 79 children presenting with poor school performance to an interdisciplinary evaluation center. Findings revealed a very high frequency of behavior problems, particularly of the internalizing type, but few differences in frequency or type of behavior problems among 4 subgroups: children with learning disabilities, mental retardation, borderline intellectual functioning, and without learning disabilities or cognitive impairment. Behavioral problems were associated with lower perceptions of self-worth and family functioning characterized as more controlling, and less supportive. Findings are discussed in terms of the need for interactional models of learning and behavior problems. PMID- 2324910 TI - Mothers' remembrances of newborn intensive care: a predictive study. AB - Six months after discharge, 94 mothers described their memories of their infant's hospitalization on an NICU. Mothers of sicker infants, those who had claimed difficulties with NICU staff, and those who felt less attached to their infant more often described painful reminders of this crisis. Pleasurable reminders were reported more often by mothers who had perceived greater personal control over their infant's recovery and had construed a purpose in this crisis. Mothers described several benefits of their memories and were more likely to do so when they had perceived a purpose in their misfortune. PMID- 2324909 TI - Social interactions between children with cancer and their peers: teacher ratings. AB - Compared children (ages 8-18) with cancer (n = 24) and matched classroom control children (n = 24) using a modified version of the Revised Class Play (RCP). A wide variety of malignancies were represented, except brain tumors. Childrens' classroom teachers completed the RCP, an instrument modified to obtain teachers' impressions of three fundamental dimensions of interpersonal style: sociability leadership, aggressive-disruptive, sensitive-isolated. Relative to the matched controls, children with cancer were perceived by teachers as (a) less sociable and prone towards leadership and (b) more socially isolated and withdrawn. These findings suggest a need for long-term psychosocial interventions oriented towards peer relationships of children with cancer. PMID- 2324911 TI - Diabetes self-care goals and their relation to children's metabolic control. AB - Undertook a goal systems analysis in order to elucidate the nature of diabetic children's cognitive representations of their health-related activities. Using a modified version of Little's (1983) Personal Projects Analysis methodology, youngsters with Type I diabetes were asked to sort health-care goals into self selected versus imposed categories. Goal dimension differences were compared via t tests, revealing that children make clear evaluative distinctions among types of diabetes-care activities. Factor analyses further revealed distinct conceptualizations for "told to do" versus "want to do" goals. When metabolic control (as measured by glycosolated hemoglobin assays) was regressed on the derived factors for selected and imposed self-care goals, none of the self selected (want to do) factors, but two of the three imposed (told to do) factors, contributed significantly to variance in HbAlc. Implications and design limitations are discussed. PMID- 2324912 TI - How adolescents compare AIDS with other diseases: implications for prevention. AB - Four hundred ten adolescents, ages 14-16 years, completed a questionnaire concerned with their understanding of the social and emotional consequences of AIDS and 5 other illnesses (lung cancer, German measles, chicken pox, asthma, and diabetes). Pupils distinguished between the diseases on all measured items, but younger pupils were more likely to believe that individuals were personally responsible for the onset of AIDS, lung cancer, and diabetes. The data are discussed in terms of the implications for health education campaigns. PMID- 2324913 TI - Monocular eye closure in sunlight. AB - Monocular eye closure in sunlight is often noted in patients with intermittent exotropia. Neither the reason for eye closure nor its frequency of occurrence in other populations is known. We questioned 147 consecutive nonoperated patients (and/or their parents) ages 1-45 years, 93 with strabismus with onset prior to 7 years of age and 54 without strabismus, for a history of closing one eye in sunlight. Monocular eye closure in sunlight was reported most frequently by patients with intermittent exotropia but was also reported by those with other forms of strabismus as well as by nonstrabismic normals. Cooperative subjects were studied further to determine the cause for eye closure. Each subject was exposed to a source of intense illumination while fixating a target. All who closed one eye under these conditions reported photalgia associated with the high light intensity, most noting less discomfort after closing one eye. None reported diplopia prior to eye closure. Monocular and binocular photophobia thresholds were then measured for each subject. The mean monocular photophobia threshold was significantly higher than the binocular threshold. In addition, binocular photophobia thresholds were significantly lower in those reporting eye closure compared with those who did not. Monocular eye closure in sunlight is a mechanism used to reduce photophobia and is not related to avoidance of diplopia. PMID- 2324914 TI - Contrast sensitivity letter charts as a test of visual function in amblyopia. AB - Anisometropic and strabismic amblyopes were studied using the Regan Contrast Sensitivity Charts. At all levels of contrast, the amblyopic eyes of both the strabismic and anisometropic patients scored significantly lower than did their fellow normal eyes, which were used as controls. In comparing the differences between the normal and amblyopic eyes of both groups, we noted a normalization of the visual function of strabismic amblyopes at low contrast. This feature was not observed in the anisometropic amblyopes who consistently scored poorly when viewing either the high or low contrast chart. PMID- 2324915 TI - An investigation of the clinical use of botulinum toxin A as a postoperative adjustment procedure in the therapy of strabismus. AB - Attempts to circumvent multiple surgical procedures are an integral part of the history of investigations in strabismus. In 1973, Botulinum toxin A (Oculinum) injections into human EOM was proposed as an alternate method to surgery for strabismus and has since proved to be effective. This article reports the results from a retrospective investigation of EOM Oculinum injection used in the postoperative period as an alternate to additional surgery. It is difficult to establish whether Oculinum altered the time span of the clinical course in these patients, but when it was effective, it provided unprecedented convenience. PMID- 2324916 TI - Amblyopia: the normal eye is not normal. AB - When acuity was used to evaluate amblyopia in children, the amblyopic eye had decreased acuity and the nonamblyopic eye had normal acuity. However when Contrast Sensitivity Functions (CSFs) were used to evaluate amblyopia, losses in the CSF were discovered in both the amblyopic and the nonamblyopic eyes. During the course of occlusion therapy, the amblyopic eye improved in acuity and CSF and the nonamblyopic eye improved in CSF. The results suggest that the nonamblyopic eye is not normal and that the CSF provides additional information to acuity about amblyopia in children. PMID- 2324917 TI - Visual acuity measurements by swept spatial frequency visual-evoked-cortical potentials (VECPs): clinical application in children with various visual disorders. AB - Previous studies have indicated that visual acuities of normal infants can be estimated with good accuracy using swept spatial frequency visual-evoked potentials (VECPs). In this report we describe acuity measurements obtained with this technique from 304 examinations performed on 135 children having various visual disorders. When possible, two or more different stimulation frequencies (8, 12, 15 or 24 contrast reversals/sec) were used in each patient, and three to eight sweep VECPs were obtained from each patient under each simulation and recording condition. High correlation coefficients (0.94 - 0.96) between the acuity estimated on each patient from either the single sweep giving the best visual acuity (BSS) or from vector averages (VeA) of the EEG data obtained from several sweeps confirmed previous findings in normal infants. We also found high correlation coefficients among BSS recorded at different temporal frequencies (0.79-0.97) and among comparisons of BSS or VeA acuity to optotype visual acuity (0.6-0.89). Children with clinically undetectable optokinetic responses showed lower visual acuity estimated by BSS than those who demonstrated optokinetic nystagmus. We conclude that the sweep VECP is a valid method, giving estimates of acuity which correlate well with optotype acuity and correspond well to other clinical findings, and that it can be useful in the clinical management of nonverbal patients. PMID- 2324918 TI - Congenital iris ectropion and a new classification for anterior segment dysgenesis. AB - Congenital iris ectropion has recently been added to the spectrum of neural-crest derived anterior segment dysgenesis syndromes. Major features include a nonprogressive ectropion of the iris pigment epithelium, a glassy smooth cryptless iris surface, a high iris insertion, dysgenesis of the drainage angle, glaucoma, and in many cases, ipsilateral ptosis. Anterior segment dysgenesis syndromes have been subdivided into disorders of neural crest cell migration, proliferation, or differentiation. The congenital iris ectropion syndrome does not clearly fit into this classification. A new classification based on a theory of developmental arrest is presented which is more consistent with current knowledge of embryologic development and with recent clinical and histopathologic findings. The new classification links the congenital iris ectropion syndrome with the Axenfeld-Rieger spectrum but separates it from classic congenital glaucoma and the irido-corneal endothelial (ICE) syndromes. In addition, a histopathologically-supported etiologic theory for congenital iris ectropion is presented that supports the new classification. PMID- 2324919 TI - Statistical properties of some clinical measures of gingivitis and periodontitis. AB - Various statistical properties of the plaque index, the gingival index, and the whole-mouth averages of pocket depth and attachment level measurements were examined using data from a 4-year randomized trial of 80 patients with a history of treated periodontal disease. Departures from normality were assessed by the median of the standardized distribution, by the coefficients of skewness and kurtosis, and by the Kolmogorov goodness-of-fit test. The relative precisions of probing pocket depth and of attachment level were measured, as were correlations between repeated measurements over time for the four clinical measures. The distribution of the plaque index was far from normal, but the distribution of its logarithm was more nearly normal. The distributions of the other clinical measures were effectively normal to varying degrees of approximation. With only rare exceptions, correlations between repeated measurements on the same clinical variable remained relatively constant no matter how far apart in time the measurements were made, at least up to 4 years. The whole-mouth mean of the attachment level measurements seemed to be relatively more precise than the whole mouth mean of the pocket depth measurements. PMID- 2324920 TI - Common problems with statistical aspects of periodontal research papers. AB - Enormous advances have been made over the past decade concerning the proper use of statistical techniques in reporting periodontal research. However, numerous articles still appear which use inappropriate or less than optimal statistical methods. This paper describes the most common problems encountered in a recent review of the literature, and presents suggestions which will hopefully improve the quality of statistical information reported in future research articles. PMID- 2324921 TI - Analgesic efficacy of flurbiprofen as compared to acetaminophen and placebo after periodontal surgery. AB - The purpose of the present investigation was to compare the analgesic efficacy of flurbiprofen, a nonsteroidal anti-inflammatory drug, which is a phenyl propionic acid derivative, with acetaminophen and placebo in 63 adult outpatients with moderate to severe dental pain following periodontal surgery. After surgery was completed under local anesthesia, the patients received under double-blind conditions an envelope containing four tablets of either flurbiprofen 100 mg, acetaminophen 500 mg, or placebo and they were instructed to take one tablet every 6 hours when postoperative pain reached moderate to severe intensity. To determine analgesic efficacy and patients recorded pain intensity on a scale of 0 to 3. Patients were allowed to remedicate after 1 hour if pain was not reduced. Flurbiprofen was shown to possess an adequate analgesic effect superior to either placebo (P less than 0.005) or acetaminophen (P less than 0.01) in the parameters studied. Our results seem to further support earlier data obtained with the drug in dental patients with postoperative pain after the surgical removal of impacted third molars; therefore, it is concluded that flurbiprofen used as directed is a new alternative for the proper treatment of pain following periodontal surgery. PMID- 2324922 TI - Susceptibility and resistance of plaque bacteria to minocycline. AB - The in vitro susceptibility of 55 strains of subgingival plaque bacteria to minocycline was determined. A concentration of 1 microgram/ml minocycline was found to inhibit 85% of the strains tested and the MIC ranged from 0.03 to 32 micrograms/ml. For 71% of the strains tested the MBC was at least 4 times greater than the corresponding MIC, suggesting a bacteriostatic activity for minocycline. A concentration of 20 mg/ml of magnesium ions was capable of neutralizing 8 micrograms/ml of minocycline and was used to eliminate "carry-over" effects inherent in the experimental procedure. After 6 to 7 weeks exposure to sub-lethal concentrations of minocycline there was no appreciable increase in the MICs of most organisms with the exception of Actinobacillus actinomycetemcomitans NCTC 10981 and Campylobacter concisus NCTC 11485. Short term (6 hour exposure of bacteria to minocycline (8 micrograms/ml) markedly reduced the viability of a number of periodontopathogens but had little effect on the viability of Veillonella parvula NCTC 11456 and Fusobacterium nucleatum NCTC 11326. These in vitro investigations have demonstrated that minocycline is capable of inhibiting most of the periodontitis-associated bacteria tested and can kill some of these bacteria after a comparatively short exposure time. However, some of the organisms tested exhibited a low susceptibility to minocycline and others became less susceptible following exposure to low concentrations of the antibiotic for several weeks. PMID- 2324923 TI - Effects on the periodontium following corticotomy-facilitated orthodontics. Case reports. AB - This report describes the corticotomy surgical technique used in conjunction with orthodontic therapy and its effect on the periodontal status of the involved teeth. The surgical procedure included intracrevicular incisions and elevation of buccal and lingual mucoperiosteal flaps. Buccal and lingual vertical grooves penetrating the cortical bone were then made between the roots. These grooves were extended from just below the interproximal alveolar bone margin to beyond the apex levels of the teeth. Buccal and lingual horizontal grooves joined the apical extensions of the vertical grooves. The orthodontic appliance was activated immediately upon wound closure. Plaque scores, probing depths, and probing attachment levels were recorded before the surgical procedure and after the completion of the orthodontic treatment in 5 patients. The results showed that the corticotomy procedure caused minimal changes in the periodontal attachment apparatus. PMID- 2324924 TI - The use of desmopressin in the management of two patients with von Willebrand's disease undergoing periodontal surgery. 2 case reports. AB - Von Willebrand's disease is a genetic bleeding disorder characterized by either a reduced plasma concentration of von Willebrand's factor (vWF) or a qualitative deficiency in that vWF which is produced. Previous therapy consisted of injecting concentrates of vWF manufactured from the pooled plasma of multiple donors. With the increased incidence and risk of serum borne transmission of such diseases as hepatitis and AIDS, the advantages of an alternative mode of therapy was obvious. In the course of using 1-desamino-8-D-arginine (desmopressin or DDAVP, a synthetic analogue of 8-arginine vasopressin, a hormone secreted in the posterior pituitary gland) in the treatment of diabetes insipidus, it was discovered that this drug causes the release of bound vWF into the plasma. The elevation lasts for several hours and is effective in producing hemostasis in some types of mild to moderate von Willebrand's disease. In 1984, desmopressin was approved for this usage in the United States. This paper discusses the use of DDAVP in the management of von Willebrand's disease and present two case reports of patients with von Willebrand's disease and in need of periodontal surgery. PMID- 2324925 TI - Selective dorsal rhizotomy: neurosurgical treatment of cerebral palsy. AB - Cerebral palsy is a syndrome characterized by abnormal motor function, with spasticity being one of the most crippling manifestations. Selective dorsal rhizotomy, a neurosurgical procedure, has successfully decreased the degree of spasticity for the child with cerebral palsy. The utilization of this procedure may enable the child with cerebral palsy to demonstrate improved motor function, creating an exciting nursing challenge. This article describes dorsal rhizotomy and the nursing care involved. The protocol of treatment and care provided at Texas Children's Hospital is also described. PMID- 2324926 TI - Riding with Bucklebear: an automobile safety program for preschoolers. AB - Almost half of the accidental deaths of children are directly attributable to motor vehicle accidents, yet many children continue to ride unrestrained. This study was designed to determine if an educational program could increase preschool children's knowledge of car safety and improve their behavior when riding in cars. Knowledge scores increased significantly following the educational program, but the use of seat belts did not change markedly. Although young children can learn self-care skills in respect to seat belt use, they apparently need strong support and reinforcement from parents in their implementation. PMID- 2324927 TI - Symbolic interactionism: a framework for the care of parents of preterm infants. AB - Because of stressors surrounding preterm birth, parents can be expected to have difficulty in early interactions with their preterm infants. Care givers who work with preterm infants and their parents can positively affect the early parental experiences of these mothers and fathers. If care givers are consciously guided by a conceptual model, therapeutic care for distressed parents is more likely to be provided. A logical framework, such as symbolic interactionism, helps care givers to proceed systematically in assessing parental behaviors, in intervening appropriately, and in evaluating both the process and outcome of the care. Selected aspects of the symbolic interaction model are described in this article and applied to the care of parents of preterm infants. PMID- 2324928 TI - The home health nurse clinician's role in the prevention of nonorganic failure to thrive. AB - Home health nurse clinicians are invaluable in the detection of children at risk for nonorganic failure to thrive (NOFTT). The literature has emphasized the role of hospital-based health care personnel in evaluating NOFTT, a strategy that relies heavily on the parent for initiation of services. Since one of the most commonly agreed-on causes of NOFTT is a disturbance in the mother-child relationship, case-finding efforts need to be community-based and less reliant on parental recognition. Because the most effective interventions take place in the child's home setting, the home health nurse clinician is in a unique position to assess the home environment for dysfunctional family interactions and behaviors and then to use the ongoing relationship with the family to implement prevention strategies for NOFTT, including teaching, modeling, and coaching effective parenting. Home-based nursing also provides the means for necessary follow-up of these families to ensure the success of the strategies. PMID- 2324929 TI - Research commitment starts at the top. PMID- 2324930 TI - Gratitude and wellness. PMID- 2324931 TI - Health care for all children. PMID- 2324932 TI - Nurses' knowledge of growth and development principles in meeting psychosocial needs of hospitalized children. AB - This study was conducted to assess nurses' knowledge of growth and developmental principles in providing psychosocial care to hospitalized children. A descriptive cross-sectional survey design was used, and a mailed questionnaire was circulated to 238 pediatric nurses. The results of the study indicate areas for improvement in the application of growth and developmental principles by pediatric nurses and suggest ways to enhance nurses' achievement in this important area of pediatric nursing practice. The findings provide direction to professionals in nursing education, clinical practice, and continuing education departments to better assist nursing personnel to use growth and developmental principles more appropriately to meet the needs of hospitalized children and their families. PMID- 2324933 TI - Information needs of mothers of children who have had liver transplants. AB - In this exploratory study, the information needs of eight mothers regarding the five liver transplant phases their children experienced were identified using Lazarus's stress framework. A 13-item, open-ended interview guide elicited information needs during the pretransplant, intraoperative, intensive care unit, recovery, and discharge phases. Using content analysis and descriptive statistics, the mothers' primary information needs were knowledge of the liver laboratory values, indications of rejection and infection, and ways to emotionally support their children. Mothers needed the most information during the pretransplant and recovery phases. PMID- 2324934 TI - Family functioning 2 to 4 years after preterm birth. AB - The purpose of the study was to determine if selected risk factors related to preterm birth continued to be associated with family functioning when preterm children were 2 to 4 years of age. A convenience sample of 55 mothers and 27 fathers participated in the survey. Parents completed the Family Dynamics Measure and the family APGAR. Multiple regression analyses were computed to examine the associations between the dependent variables for family functioning and the independent variables, which included child's developmental status, neonatal hospitalization length, adequacy of family economics, parental age, and marital status. Of these risk factors, longer neonatal hospitalizations continued to be associated with poorer family role functioning for mothers (R2 = .237, F = 2.43, p = .039). PMID- 2324935 TI - The suppression of exciting thoughts. AB - We examined how the suppression of an exciting thought influences sympathetic arousal as indexed by skin conductance level (SCL). Subjects were asked to think aloud as they followed instructions to think about or not to think about various topics. Experiment 1 showed that trying not to think about sex, like thinking about sex, elevates SCL in comparison to thinking about or not thinking about less exciting topics (e.g., dancing). Experiment 2 revealed that the suppression of the thought of sex yielded SCL elevation whether or not subjects believed their think-aloud reports would be private or public, and it also revealed that the effect dissipated over the course of a few minutes. Experiment 3 found such dissipation again but showed that subsequent intrusions of the suppressed exciting thought are associated with further elevations in SCL over 30 min. Because such an association was not found when subjects were trying to think about the exciting thought, it was suggested that the suppression of exciting thoughts might be involved in the production of chronic emotional responses such as phobias and obsessive preoccupations. PMID- 2324936 TI - Interpersonal perception in a social context. AB - Interpersonal perception among well-acquainted individuals in a social context was studied. High acquaintance was expected to provide perceivers with a large sample of target behaviors across situations. In turn, memory for acquaintances should be organized by social group and personality characteristics, as predicted by the social context-personality index theory. Differentiation of the target's traits in memory should produce a target effect on perception that is stronger than the perceiver effect. Furthermore, evidence for accuracy, meta-accuracy, independence of self- and other-perception, and reciprocity of affect were anticipated. A social relations analysis of data from a multiple-interaction, reciprocal design was used to study these phenomena. At the individual level, analyses indicated that perceptions of targets were determined primarily by target characteristics and secondarily by perceiver construction of the judgment. Also, perceivers judged targets as targets judged themselves, and targets knew in general how perceivers viewed them. Self- and other-perceptions were largely independent. Surprisingly, we did not observe dyadic meta-accuracy. PMID- 2324937 TI - Transition to motherhood and the self: measurement, stability, and change. AB - Different ways of conceptualizing and measuring change in attitudes during transition to motherhood are examined. A series of analyses was performed on data from a cross-sectional sample (N = 667) and a smaller longitudinal sample (n = 48) to demonstrate sound psychometric properties for 2 new scales and to show construct comparability across different phases of childbearing. For Childbearing Attitudes Questionnaire, results demonstrated equality of covariance for 16 scales and comparability of structure and meaning of 4 higher order factors- identification with motherhood, social orientation, self-confidence, and negative aspects of giving birth. For Mothering Self-Definition Questionnaire, results demonstrated equality of covariance of 5 scales and comparability of structure and meaning of a single higher order factor, interpreted as reflecting positive feelings about one's mothering characteristics. Analyses of correlations and mean differences identified areas of change and stability. PMID- 2324938 TI - Mechanisms governing empowerment effects: a self-efficacy analysis. AB - This experiment tested the hypotheses that perceived coping and cognitive control self-efficacy govern the effects of personal empowerment over physical threats. Women participated in a mastery modeling program in which they mastered the physical skills to defend themselves successfully against unarmed sexual assailants. Multifaceted measures of theoretically relevant variables were administered within a staggered intragroup control design to test the immediate and long-term effects of the empowerment program and the mechanisms through which it produced its effects. Mastery modeling enhanced perceived coping and cognitive control efficacy, decreased perceived vulnerability to assault, and reduced the incidence of intrusive negative thinking and anxiety arousal. These changes were accompanied by increased freedom of action and decreased avoidant behavior. Path analyses of causal structures revealed a dual path of regulation of behavior by perceived coping self-efficacy, one mediated through perceived vulnerability and risk discernment and the other through perceived cognitive control self-efficacy and intrusive negative thinking. PMID- 2324939 TI - Dimensionality of coping and its relation to depression. AB - The dimensionality of coping, as measured by 65 items from 3 commonly used instruments, and the relation of coping and stress to concurrent and future depression were studied in a community sample of 742 older (greater than or equal to 50 years old) adults. Measures of coping, stress, and depression were obtained at 2 time points over a 2-year period. Depression was assessed by symptom checklist and by diagnostic interview. Three coping factors--Cognitive Self Control, Ineffective Escapism, and Solace Seeking--that had adequate psychometric properties and accounted for 25% of the total item variance were identified. Ineffective Escapism was associated with current depression and had a direct and interactive effect on future depression, exacerbating the negative impact of stress rather than acting as a buffer. Although Cognitive Self-Control was unrelated to either concurrent or future depression, Solace Seeking significantly buffered the effect of stress in predicting a future diagnosis of depression. Stress and initial depression level predicted both measures of future depression. Gender (being female) predicted the future diagnosis of depression but not the increase of depressive symptoms. PMID- 2324940 TI - Impulsive motor behavior: effects of personality and goal salience. AB - This experiment used a circle tracing paradigm to extend our recent theoretical development concerning the contributions of extraversion and neuroticism to impulsive performance on continuous motor tasks. Subjects (N = 137) completed the Eysenck Personality Questionnaire and were randomly assigned to 1 of 2 circle conditions: The goal condition provided subjects with a salient behavioral end point for their tracings, whereas the no-goal condition promoted behavioral uncertainty. In both conditions, Ss were asked to trace the circle under neutral and inhibition instructions. Using Gray's impulsivity and anxiety dimensions to group subjects, impulsive subjects under inhibition instructions displayed significantly faster tracing speed than nonimpulsive subjects in the presence of a salient goal, whereas anxious subjects appeared behaviorally impulsive in a situation promoting uncertainty and response conflict. Conceptualizing impulsivity and anxiety in terms of extraversion and neuroticism, with impulsive Ss as neurotic extraverts and anxious Ss as neurotic-introverts, it is proposed that Ss' level of extraversion determines the type of stimuli to which they are responsive, and that level of neuroticism influences the magnitude of this reaction. PMID- 2324941 TI - Effects of responses to depression on the remediation of depressive affect. AB - The effects of different types of responses to a depressed mood on the duration and severity of the mood were examined. On the basis of Nolen-Hoeksema's (1987) response styles theory of depression, it was hypothesized that distracting, active responses would be more effective in alleviating a depressed mood than would ruminative, passive responses. A depressed mood was induced in 35 male and 34 female Ss, and subjects were randomly assigned to engage in 1 of 4 types of responses: an active task that distracted them from their mood; a passive, distracting task; an active task designed to lead to ruminations about their mood; or a passive, ruminative task. As predicted, the greatest remediation of depressed mood was found in Ss in the distracting-active response condition, followed in order by the distracting-passive, ruminative-active, and ruminative passive response conditions. Degree of rumination had a greater impact on remediation of depressive affect than level of activity, with greater rumination leading to lesser remediation of depressive affect. In addition, the effects of the response tasks were limited to depressed mood. The implications of these results for interventions with depressed persons are discussed. PMID- 2324942 TI - Accelerating the coping process. AB - On the basis of previous work, freshmen should evidence improved health after writing about their thoughts and feelings associated with entering college. One hundred thirty subjects were assigned to write either about coming to college or about superficial topics for 20 min on 3 days. One fourth of the subjects in each group wrote during the 1st, 5th, 9th, or 14th week of classes. Physician visits for illness in the months after writing were lower for the experimental than for the control subjects. Self-reports of homesickness and anxiety were higher in the experimental group 2-3 months after writing. By year's end, experimental subjects were either superior or similar to control subjects in grade average and in positive moods. No effects emerged as a function of when people wrote, suggesting that the coping process can be accelerated. Implications for comparing insight treatments with catharsis and for distinguishing between objective and self report indicators of distress are discussed. PMID- 2324943 TI - The efficacy and clinical impact of brain imaging in neurologically symptomatic AIDS patients: a prospective CT/MRI study. AB - The relative efficacies of cranial magnetic resonance imaging (MRI) and computed tomography (CT) brain scans for the detection of intracranial pathology in patients with the acquired immune deficiency syndrome (AIDS) were evaluated prospectively. Fifty homosexual or bisexual men with AIDS and neurologic symptoms were evaluated using both modalities. In 24 patients, MR images and CT scans provided the same diagnostic information (within normal limits in 16, cerebral atrophy only in 6, and similar lesions in 2 patients). In only one instance did CT show the presence of a lesion not seen on MRI. In the 25 remaining patients, MRI was the more sensitive modality. MRI also reflected more consistently the histopathologically documented extent and distribution of central nervous system disease. The greater sensitivity of MRI suggested significant alterations in the diagnostic evaluation and therapeutic management of 20 patients. Thus, MRI was as good or better than CT for the detection of intracranial pathology in 49 of 50 neurologically symptomatic AIDS patients and significantly affected the diagnosis and treatment of 40% of these patients. Although MRI does not appear to be more specific than other modalities in the differentiation of human immunodeficiency virus (HIV)-related neurologic diseases, its greater sensitivity suggests that MRI may be the best neuroimaging procedure for the initial radiologic evaluation of AIDS patients with neurologic illness. PMID- 2324944 TI - Cryptococcus neoformans pulmonary infection in HIV-1-infected patients. AB - Cryptococcus neoformans (Cn) is a frequent pathogen in patients infected with the human immunodeficiency virus (HIV-1). We review the initial presentation and clinical course of 18 HIV-1-infected (HIV+) patients with a Cn pulmonary infection. Simultaneous positive cerebrospinal fluid (CSF) cultures were found in 10 (63%) of 16 examined. The most frequent presenting symptoms were fever (87%) and pulmonary complaints (60%). Although the most common chest radiographic finding was bilateral diffuse interstitial infiltrates, nodules and cavitary lesions were also seen. Nine (50%) of the 18 patients died within 6 weeks of diagnosis. Of six patients with an isolated Cn pulmonary infection, five have subsequently died. Three of these five patients did not receive maintenance therapy and had confirmed or probable relapse. Patients initially presenting with an isolated Cn pulmonary infection may later show disseminated disease, suggesting that such patients should receive both acute and maintenance therapy. PMID- 2324945 TI - Detection and characterization of HIV-1 by polymerase chain reaction. AB - Recently a new technique, the polymerase chain reaction (PCR), has been used for the detection and characterization of HIV-1 proviral DNA and viral RNA. These reports support the notion that the PCR is more sensitive and specific than other established HIV-1 detection techniques. However, due to its extreme sensitivity, the PCR is highly susceptible to contamination, resulting in false positive results. To avoid contamination, strict rules on sample preparation and pre- and post-PCR handling are required. Confirmation of both positive and negative PCR results by independent techniques is not always feasible, and, therefore, optimal PCR conditions, inclusion of control samples, repetition of results, and confirmation of specificity by hybridization are required. The choice of the material from which HIV-1 is amplified, the primers used for amplification as well as the PCR conditions will determine what is actually amplified. PMID- 2324946 TI - Determination of anti-cardiolipin and other antibodies in HIV-1-infected patients. AB - Anti-cardiolipin antibodies (ACA) were determined by an ELISA assay in 116 HIV-1 infected patients. A positive test was found in 27 patients (23.3%) with a predominance of IgG ACA isotype. No significant difference in ACA positivity was observed between homosexuals (22.2%) and intravenous drug users (25.8%). The presence of different immunological markers was compared in ACA-positive and ACA negative patients: ACA-positive patients had higher IgG levels (p less than 0.05) and a tendency to higher frequencies of anti-ss DNA, anti-ds DNA, anti-i antibodies, as well as circulating immune complexes. When patients were classified according to CDC criteria, no significant difference was observed for the prevalence of ACA in class II (21.2%), in class III (25%), and in class IV (21%). Our results indicate that ACA antibodies occur with other immunological alterations in HIV-1-infected patients, but do not confirm that ACA is a useful prognostic marker for development of AIDS. PMID- 2324947 TI - No evidence of HIV-2 infection in Argentina. PMID- 2324948 TI - Isolated LH deficiency in an AIDS patient. PMID- 2324949 TI - Prenatal diagnoses of HIV infection. PMID- 2324950 TI - Mobilizing the field of child psychiatric nursing for participation in the national plan for children and adolescents. PMID- 2324951 TI - Young people and AIDS. Mental health promotion in action. AB - This article describes the development and implementation of a two part health promotion and primary mental health prevention program developed for junior high students. AIDS education was used as a vehicle for promoting the development of a responsible decision-making framework in the students. Both cognitive and affective learning strategies were used in the program. The reactions of the students, their parents, and the educational system are described. PMID- 2324952 TI - The role of the psychiatric/mental health nurse clinical specialist in an adolescent coping skills group. AB - The psychiatric/mental health nurse clinical specialist is a professional who brings unique skills to the area of mental health prevention. Adolescents are an at-risk population in need of preventive mental health services. This article describes the unique features of a nurse-led adolescent prevention program. A specific Adolescent Coping Skills Group format, which uses the skills of the master's prepared psychiatric nurse, is presented. PMID- 2324953 TI - Developmental history collection on a child psychiatric inpatient service. AB - This retrospective study was the first step of a larger project aimed at constructing a data collection tool to be used by child psychiatric nurses on an acute psychiatric inpatient service. A sample of 41 records was reviewed by a single reviewer using explicit criteria to determine the quality of data currently being gathered. The sample was randomly selected from 180 records of children admitted to an acute child psychiatric inpatient service in a major teaching institution. Of the 41 records reviewed, 14 had little or no information concerning the child's developmental course, and in about 50% of the charts similar information was recorded by different team members. It was noted that this service is fairly new, and no assessment tool that reflects a consensus of the multidisciplinary team is currently in use. Without a systematic method of gathering data upon admission, data collection will continue to be inconsistent and incomplete. PMID- 2324955 TI - Review of the Institute of Medicine report on children and adolescents. PMID- 2324954 TI - Strategies of normalization used by parents of chronically ill school age children. AB - The concept of normalization is examined in relation to chronically ill children. From this conceptual base, the responses of 365 parents in a survey of chronically ill children's use of time out of school, were analyzed to determine the normalization strategies used pertaining to the life of the child and family. This article discusses the appropriateness and importance of normalization, and presents implications for the professional nurse working with families of chronically ill children. PMID- 2324956 TI - Issues facing child psychiatric nursing in the 1990s. PMID- 2324957 TI - Percutaneous absorption, metabolic profiling, and excretion of the penetration enhancer azone after multiple dosing of an azone-containing triamcinolone acetonide cream in humans. AB - Radioactive Azone (1.6%; 1-dodecylazacycloheptan-2-one) was incorporated in a therapeutic formulation containing triamcinolone acetonide at a concentration of 0.05%. This cream (TAZ) was applied for four consecutive days to human volunteers on the same 24-cm2 application area on the forearm for 12 h under occlusion. The percutaneous absorption of Azone as measured in the excreta appeared to be only 3.47 +/- 0.33% during the whole study period. Azone-derived radioactivity was predominantly excreted by the kidneys (97.8 +/- 0.4%). From the urinary excretion plot, it could be deduced that the flux of Azone through human skin increased during the study period, reaching a plateau within 2-3 d. Accumulation of Azone in the stratum corneum did not occur. Only unchanged Azone could be detected in the stratum corneum. Excretion was mainly in the form of very polar metabolites. Compared with pure Azone, the therapeutic formulation did not influence the metabolism, excretion route, or urinary elimination rate of the penetration enhancer. PMID- 2324958 TI - Bioadhesive lozenge for the improved delivery of cetylpyridinium chloride. AB - Conventional lozenges produce a high initial release of drug in the oral cavity, which rapidly declines to subtherapeutic levels, and requires multiple daily administration with associated problems of systemic toxicity and compliance. Various multilayer compacts containing cetylpyridinium chloride were evaluated in vitro using release into simulated saliva (buffer pH 6.6). The drug loading, the wax content of the active layer, and the composition of the bioadhesive layer were important variables affecting product performance. Following preliminary in vivo studies, the release of a three-layered device containing drug in a nonadhesive and flavored waxy exposed layer was studied in six humans using HPLC and was shown not to be affected by location within the mouth. In comparison with a proprietary lozenge formulation, the device produced more uniform and effective levels of drug (approximately 20 micrograms.mL-1), with adequate comfort, taste, and irritancy over a period of 3 h. PMID- 2324959 TI - In vitro dissolution and in vivo bioavailability of commercial levothyroxine sodium tablets in the hypothyroid dog model. AB - The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of levothyroxine sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of levothyroxine sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (micrograms per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka). PMID- 2324960 TI - Slow-release characteristics of diltiazem from ethylated beta-cyclodextrin complexes. AB - Release characteristics of two ethylated beta-cyclodextrins [heptakis(2,6-di-O ethyl)-beta-cyclodextrin (diethyl-beta-cyclodextrin) and heptakis(2,3,6-tri-O ethyl)-beta-cyclodextrin (triethyl-beta-cyclodextrin)] as sustained-release drug carriers were evaluated using diltiazem hydrochloride, a water-soluble calcium antagonist. The release rate of diltiazem from compressed tablets was significantly retarded by the complexation with ethylated beta-cyclodextrin. Various environmental effects (such as pH, rotating speed, and additive in the dissolution medium) on the release rate were investigated, together with a microscopic observation of the tablet surface. The water penetration rate into the tablet was measured in order to gain insight into the release mechanism. The results suggested that diltiazem is released slowly from the hydrophobic matrix consisting of diethyl-beta-cyclodextrin following water penetration. When a single dose of tablets containing diethyl-beta-cyclodextrin complex was orally administered to dogs, the sustained-release pattern of the drug, without decrease in area under the plasma concentration-time curve, was produced for a long period. The release rate of diltiazem can be controlled by combining the ethylated beta-cyclodextrin complexes with the parent beta-cyclodextrin complex in different mixing ratios. PMID- 2324961 TI - Quantum chemical study of the electronic and conformational characteristics of adenosine and 8-substituted derivatives: functional implications in the mechanism of reaction of adenosine deaminase. AB - A quantum chemical study of 10 substrates of adenosine deaminase is performed. The conformational preference around the glycosidic bond of several 8-substituted derivatives of adenosine is studied using semiempirical modified neglect of diatomic overlap (MNDO) and Austin model 1 (AM1) methods. All the compounds studied show preference for the anti conformation; the syn - anti energetic differences calculated are small and in excellent agreement with experimental data. A relationship between the ab initio molecular electrostatic potential minimum energy of N3 and the syn - anti energetic difference is found. A highly significant relationship is also found between the ab initio net charge over the purine and pyrimidine rings and the logarithm of the maximum rate of deamination (log Vm) of the nucleosides by adenosine deaminase. In contrast, no significant relationship is found between the anti preference of 8-substituted derivatives of adenosine and their log Vm of deamination. PMID- 2324962 TI - Mechanism of hydrolysis and structure-stability relationship of enaminones as potential prodrugs of model primary amines. AB - The objective of this work was to investigate the chemistry and the structure stability relationship of enaminones (a class of enamines formed between a primary amine and a 1,3-dicarbonyl compound) and to evaluate their potential usefulness as prodrugs of primary amines. The acid-catalyzed degradation of the enaminones was found to be very sensitive to minor differences in the structure of the 1,3-dicarbonyl compound used to form the enaminone, but relatively insensitive to changes in the amine portion of the enaminones. A correlation was found between the rate of enaminone hydrolysis and the pKa of the 1,3-dicarbonyl compound, suggesting that the rate-controlling step in the hydrolysis of the enaminones was the proton addition to the vinyl carbon of the enaminone. Enaminones formed with cyclic 1,3-dicarbonyl compounds were significantly more stable than those formed with structurally similar acyclic compounds. Based on chemical stability considerations alone, enaminones do not appear to be good candidates as prodrugs of primary amines. Evidence is presented, however, that enaminones formed between amines and 1,3-ketoesters or lactones may be subject to enzyme-catalyzed degradation. Further research on the design of enaminones destabilized by a triggering enzymatic event that results in the loss of conjugation (e.g., ester or lactone hydrolysis or an oxidation/reduction event) may prove worth pursuing. PMID- 2324963 TI - Modeling the uniaxial compaction of pharmaceutical powders using the mechanical properties of single crystals. I: Ductile materials. AB - A model is presented which uses the Vickers microindentation hardness of ductile crystals such as sodium chloride to predict the uniaxial compaction behavior of compacts. A general approach first developed in the materials science field to predict the densification of particulate matter under hydrostatic loading was followed. However, modifications to account for the effects of particle geometry and the closed-die loading conditions were considered. Using the standard microindentation hardness value of sodium chloride, the model predicted the densification behavior of this material at a punch displacement rate of 1 mm/min. Densification at higher compaction rates was predicted by considering the effect of deformation kinetics on the hardness. Secondary factors which affect compaction, such as particle size effects and die-wall friction, are also briefly discussed. PMID- 2324964 TI - A corneal perfusion device for estimating ocular bioavailability in vitro. AB - An in vitro method for investigating drug penetration across the cornea from acute doses has been developed. The donor (epithelial or tear) side of a corneal chamber similar to those used by Edelhauser and co-workers was modified with a reduced-volume insert so that the donor side volume approximated 6% of the receiver (endothelial or aqueous humor) chamber volume. Fluid was pumped through the anterior chamber to simulate the physiologic tear turnover in vivo. The receiver chamber was bubbled with oxygen:carbon dioxide (95%:5%) to aerate and circulate the fluid. We investigated the in vitro ocular bioavailability of several marketed ophthalmic drug formulations using this model (0.03% flurbiprofen, 0.5% levobunolol, 0.1 and 0.25% fluorometholone, and 1% prednisolone acetate). At 1 min after the dose administration, drug was eluted from the donor chamber at a dose turnover rate of 12%/min. In all experiments, a small percentage of the applied dose penetrated the cornea. Using this chamber device, the ocular bioavailability via corneal absorption ranged between 5 and 16% for solution formulations, whereas the ocular bioavailability for the suspension formulations was less than 0.3%. The major portion of the administered dose was recovered from the donor side effluent. This observation was consistent with findings showing low ocular bioavailability of ophthalmic preparations due to the rapid precorneal washout in vivo. The extent of drug penetrating as its corneal metabolite in the model correlated well to in vitro corneal metabolism rate constants. The new model opens several potentially useful areas of research into ocular absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2324965 TI - Structure of amiprilose hydrochloride, a novel anti-inflammatory agent. AB - Amiprilose hydrochloride is a carbohydrate-derived, novel anti-inflammatory with potential application in the treatment of rheumatoid arthritis. A spectroscopy based approach was undertaken to assign both the relative and absolute configuration of its five chiral centers. The fully assigned 13C and 1H NMR spectra of amiprilose hydrochloride was used to establish the relative stereochemistry of four of its five chiral centers held rigid in its furanose ring system. Parallel synthesis of the enantiomer of amiprilose hydrochloride from L-glucose was followed by CD spectropolarimetry to establish that no inversion of chiral centers had occurred in the synthesis. The hydrobromide salt of amiprilose and its enantiomer were prepared and, together with amiprilose hydrochloride, were crystallized. X-ray crystallographic analysis resulted in the assignment of the absolute configuration of all five chiral centers. PMID- 2324966 TI - Dissolution testing of norethindrone:ethinyl estradiol, norethindrone:mestranol, and norethindrone acetate:ethinyl estradiol combination tablets. AB - Dissolution of oral contraceptive combination products from six manufacturing firms was studied utilizing the rotating basket method at 100 rpm in 600 mL of 0.1 M HCl and 0.02% sodium lauryl sulfate (SLS). Most of the combination products of norethindrone (NE):ethinyl estradiol (EE) dissolved satisfactorily in water using the paddle method which was first proposed by U.S.P., whereas three of 18 tested products showed better dissolution in acidic aqueous medium containing SLS. Acidic medium with surfactant was also found to be suitable for combination products of norethindrone (NE):mestranol (ME) and norethindrone acetate (NEAc):ethinyl estradiol (EE). A modified U.S.P. assay procedure, a reversed phase high-performance liquid chromatographic (HPLC) method with a mobile phase of acetonitrile and phosphate buffer, was used to analyze NE and EE concurrently. The NEAc and ME were analyzed separately in these combination products. The NEAc was found to hydrolyze to some extent (approximately 20% in 8 h) in acidic dissolution medium at room temperature, but less so at 4 degrees C. The NE was identified as the sole degradation product of NEAc hydrolysis and was also measured to account for the total amount of NEAc dissolved. A simple dissoluting testing method which utilizes a single dissolution medium was applicable for all oral contraceptive combination tablets surveyed. PMID- 2324967 TI - Synthesis of 11-phenyl-2,3,4,5-tetrahydro-1H-(1,4)diazepino(1,2-a)indoles and 1 (3-aminopropyl)-2-hydroxymethyl-3-phenylindoles as 5-hydroxytryptamine antagonists. AB - A series of novel 11-phenyl-2,3,4,5-tetrahydro-1H-(1,4)diazepino(1,2-a) indoles (5a-f) and 1-(3-aminopropyl)-2-hydroxymethyl-3-phenylindoles (6a-f) are reported. The compounds (5a-f) were prepared by the lithium aluminum hydride (LAH) reduction of corresponding 11-phenyl-1H-1-oxo-2,3,4,5 tetrahydro(1,4)diazepino(1,2-a)indoles (4a-f). The precursors (4a-f) were, in turn, prepared by the catalytic reduction of 1-(2-cyanoethyl)-3-phenylindole-2 carboxylates (2a-f) and cyclization of the resulting 1-(3-aminopropyl)-3 phenylindole-2-carboxylates (3a-f) with sodium hydride in xylene. The LAH reduction of 2a-f gave exclusively 1-(3-aminopropyl)-2-hydroxymethyl-3 phenylindoles (6a-f) and not the diazepinoindoles (5a-f) which were expected. The title compounds and the intermediates have been screened for their anti-5 hydroxytryptamine (anti-5-HT) activity. The most potent anti-5-HT compounds of this series, 6a and 6e, were found to be weak compared with cyproheptadiene, a standard anti-5-HT drug. PMID- 2324968 TI - A novel differentiation method of vehicle models for topically applied drugs: application to a therapeutic timolol patch. AB - A novel method to differentiate basic vehicle models for topically applied drugs is proposed. In this method, the rate of drug release as a function of time, obtained by using a flow-through cell, is plotted on both semilogarithmic and logarithmic scales. In the Solution Case, where all of the drug is dissolved in the vehicle, the profiles become linear on the semilogarithmic scale. However, in the Suspension Case, where the initial drug amount per vehicle volume is greater than the solubility of the drug and the vehicle contains finely dispersed drug, the profiles are linear on the logarithmic scale with a slope of -0.5. They abruptly depart from this pattern upon depletion of the suspended phase. The different attributes of the profiles for the drug release rate-time curves in these two cases can be visualized more clearly when vehicle thickness and drug concentration are varied. The theoretical principles are illustrated in profiles for the drug release-rate time plots of therapeutic patches containing the beta blocker timolol. This was formulated at different concentrations in an acryl copolymer with varied thickness. The release profiles were best fitted to the Solution Case treatment of the data. PMID- 2324969 TI - On the mechanism of isomerization of cephalosporin esters. PMID- 2324970 TI - Stable isotope coadministration methodology for the estimation of the fraction of imipramine metabolized to desipramine. AB - The application of a stable isotope coadministration technique for estimating the fraction (fm) of imipramine (IP) that is converted to desipramine (DMI) is described. Four healthy male subjects received 25 mg of IP-d4 hydrochloride orally with 25 mg of DMI hydrochloride. The plasma concentrations of IP-d4, DMI d4, and DMI were determined by capillary gas chromatography-mass spectrometry selected ion monitoring using d8 analogues as internal standards. The fm values, calculated from the ratio of the area under the plasma concentration-time curve of DMI-d4 to that of DMI, varied from 0.54 to 0.85. PMID- 2324971 TI - Pharmacokinetics of piperacillin in patients on peritoneal dialysis with and without peritonitis. AB - The pharmacokinetics of piperacillin given intravenously (1 or 2 g) to nine patients with chronic renal failure and undergoing continuous ambulatory peritoneal dialysis was intermediate between values obtained in healthy volunteers and in patients with renal insufficiency studied between dialyses: half-life, 2.4 h; total clearance, 100 mL/min; urinary or peritoneal clearance, 3 mL/min. The intraperitoneal administration of piperacillin in dialysis fluid (400 mg or 1 g to five patients) increased the half-life (6 to 7 h) and decreased the volume of distribution of about two thirds. In both instances, the area under the curve was well correlated with dosage. The absorption of piperacillin by an inflamed peritoneum in eight patients suffering from peritonitis and treated with 400 mg, 1 g, or 2 g, was increased and returned to normal concurrently with care. Consequently, the recommended dosage is intravenous administration of 2 g of piperacillin every 8 h or intraperitoneal administration of 1 g every 6 h in the dialysate. With such conditions, serum concentrations greater than minimal inhibitory concentrations and sufficient to avoid dissemination of piperacillin susceptible organisms without risk of accumulation are obtained. PMID- 2324972 TI - Radiographic anatomy of the first metatarsal. AB - Normal radiographic anatomy of the first metatarsal bone is established through cadaver dissection, examination of bone specimens, and radiography. Extra articular and distal articular anatomical landmarks are identified with wire markers. Dorsoplantar, lateral, lateral oblique, and medial oblique radiographs of 15 osteologic sites are presented, including the articular margins of the first metatarsal head, the borders of the three diaphyseal surfaces, the origins of the metatarsophalangeal collateral and metatarsosesamoid suspensory ligaments, and the insertions of the first cuneiform-metatarsal joint ligaments and the tibialis anterior and peroneus longus tendons. The correlation of gross anatomy and radiographs is described. PMID- 2324973 TI - Anatomical and histologic investigation of the syndesmotic area in the ankle joint. AB - The syndesmotic area in the ankle joint is analyzed by reviewing the literature and by examining its gross anatomy and histology. Seventy-five ankles were dissected and examined, with an emphasis on the syndesmotic area. The gross anatomical results of this study differ somewhat with those of other authors. The average height, attachments, consistency, color, and shape are reported. In addition to gross examination, four ankles were examined histologically, and the findings are discussed. The results of this study define in detail the anatomy of the syndesmotic area. PMID- 2324974 TI - Review of metatarsal osteotomies for the treatment of neuropathic ulcerations. AB - The records of 52 patients who underwent metatarsal osteotomies for the treatment of chronic neuropathic ulcerations between the years 1983 and 1985 were analyzed in a retrospective study. Long-term follow-up information was available for all but three patients. All patients were conservatively managed preoperatively and postoperatively with shoes, accommodative orthoses, and local care. A limb salvage rate of 94%, 46 of 49 patients, was achieved in this study. Although 13 patients developed transfer ulcerations, all but one were managed either with conservative care or a lesser podiatric procedure, and all remain healed to date. PMID- 2324975 TI - Sinus tarsi syndrome in a patient with talipes equinovarus. AB - The literature reports that 70% of the cases of sinus tarsi syndrome are post traumatic, following an inversion sprain, and that 30% result from inflammatory disorders, such as rheumatoid arthritis, ankylosing spondylitis, and gouty arthritis. However, in the case presented, talipes equinovarus deformity and sinus tarsi syndrome coexisted. One of the corrective goals in the management of the talipes equinovarus deformity is the realignment of the articulation between the medial plantarly deviated talar head and the anteromedial segment of the calcaneus. The calcaneus must be rotated from a plantarflexed position into a dorsiflexed position. The posterior tubercle will be moved down and in, with the anterior process moved up and out away from the talar head. By correcting the plantarflexed varus attitude of the calcaneus, it is put in a valgus position that often closes down the sinus tarsi upon weightbearing. This compression may result in pain over the lateral aspect of the midfoot with hindfoot instability, as seen in the case presented. As a result of the abnormal anatomical relationship of the talus and calcaneus, the patient developed severe pain in the sinus tarsi. Based on the medical history and present postoperative results, the authors find a long-term sequela of talipes equinovarus deformity to be sinus tarsi syndrome. PMID- 2324977 TI - Communication--the key to success. PMID- 2324976 TI - Leiomyosarcoma of the cutaneous tissue. A case occurring in the ankle and foot. PMID- 2324978 TI - Nursing interventions with the antepartum substance abuser. PMID- 2324979 TI - Occupational health hazards: implications for perinatal and neonatal nurses. PMID- 2324980 TI - Nursing intervention with mothers who are substance abusers. PMID- 2324981 TI - Voltage dependence of Ia reciprocal inhibitory currents in cat spinal motoneurones. AB - 1. Inhibitory postsynaptic currents (IPSCs) were recorded in voltage clamped posterior biceps or semitendinosus motoneurones of the cat during reciprocal inhibition. 2. Population IPSCs, recorded following stimulation of the whole quadriceps muscle nerve, had an average time-to-peak of 0.51 +/- 0.02 ms (+/- S.E.M., n = 22) and decayed exponentially, with an average time constant of 0.99 +/- 0.04 ms (at 37 degrees C) at resting membrane potentials. 3. Unitary IPSCs, recorded following spike-triggered averaging from an identified reciprocal inhibitory interneurone, had amplitudes of 120-220 pA with an average time-to peak of 0.40 +/- 0.06 ms (n = 5). The decay of these unitary currents was exponential, with an average time constant of 0.82 +/- 0.07 ms (at 37 degrees C) at resting membrane potentials. 4. The time course of IPSCs was unaffected by either alpha-chloralose or pentobarbitone at concentrations necessary for deep anaesthesia. 5. The peak synaptic current varied linearly with the membrane potential over the range -90 to -30 mV, and had an average reversal potential of 80.7 +/- 1.5 mV (+/- S.E.M., n = 6) when measured using KCH3SO4-filled electrodes. 6. The reversal potential for the IPSC was used to calculate [Cl-]i. This was estimated to be 6.5 mM assuming that the inhibitory synaptic current was mediated purely by Cl- ions. 7. The rate at which synaptic currents decayed was exponentially dependent on the postsynaptic membrane potential, the decay time constant increasing e-fold for a 91 mV depolarization. This result was independent of [Cl-]i or of the magnitude of the synaptic conductance and was interpreted as a voltage dependence of the glycine channel open time. 8. The average unitary peak conductance was 9.1 +/- 1.7 nS (+/- S.E.M., n = 5), corresponding to the opening of approximately 200 glycine-activated postsynaptic channels following neurotransmitter release from a single Ia reciprocal interneurone. PMID- 2324982 TI - Muscarinic agonists and ATP increase the intracellular Ca2+ concentration in chick cochlear hair cells. AB - 1. Cholinergic muscarinic agonists applied by the pressure puff method increased intracellular Ca2+ concentration in Fura-2-loaded hair cells. The Ca2+ response outlasted the agonist application. 2. The Ca2+ response induced by acetylcholine (ACh) was ACh dose dependent with a KD of 200 microM. Desensitization was negligible, and almost identical Ca2+ responses were observed when two ACh puffs were separated by 150 s. The response was blocked by d-tubocurarine (dTC). The KD of dTC blocking was 500 microM when 100 microM-ACh induced the Ca2+ response. 3. The amplitude of the ACh-induced Ca2+ responses were potentiated to 3 times the control by incubation with calcitonin gene-related peptide (CGRP; 0.1-1 microM). CGRP did not affect the resting Ca2+ concentration. Glycine (100 microM) potentiated the ACh response to 1.4 times the control, and also increased the resting Ca2+ concentration slightly. 4. The ACh-induced Ca2+ response was suppressed by atropine. It was induced in Ca2(+)-free extracellular medium, and in Ca2(+)-free medium desensitization to a second ACh stimulation was significant. The amplitude of the second Ca2+ response was 44% of the first when two ACh puffs were separated by 117 s in Ca2+ free medium. 5. Muscarine and carbamylcholine induced similar Ca2+ responses, with KD values of 130 microM for muscarine and 340 microM for carbamylcholine. Desensitization of Ca2+ responses was negligible in both agonists. 6. ATP co-exists with ACh in some presynaptic nerve terminals (Burnstock, 1981). Puff-applied ATP (100 microM) generated a Ca2+ response with a rapid rising phase and a following slow phase. In Ca2(+)-free medium the rapid phase disappeared and only the slow phase was observed. The rapid phase is due to the influx of Ca2+ ions and the slow phase is due to a release of Ca2+ ions from an intracellular reservoir. Under voltage clamp ATP induced a fast inward current and a following slow outward current. 7. Nicotine, adenosine, glycine, GABA, glutamate and bradykinin did not induce Ca2+ responses in the hair cell. 8. ACh induced hyperpolarization of the hair cell membrane under current clamp, most probably by the activation of Ca2+ activated K+ conductance. Therefore, a cholinergic muscarinic receptor may mediate the inhibitory effects of efferent innervation observed in hair cells. PMID- 2324983 TI - The uptake of radiolabelled precursors of mucus glycoconjugates by secretory tissues in the feline trachea. AB - 1. We gave one of three radiolabelled precursors of mucus glycoconjugates ([3H]proline, [3H]glucose and [35S]sulphate) into the tracheas of anaesthetized cats for 3 h. In other cats [35S]sulphate was given by intravenous injection. 2. After a further 2 h, tracheas were removed and fixed. Serial actions were cut and alternate sections were stained with Haematoxylin and Eosin or prepared as unstained autoradiographs. Points on submucosal gland and surface epithelium were chosen with a grid on photomicrographs of the stained sections. Absorbance, which is proportional to autoradiographic grain density, was estimated on corresponding points on unstained autoradiographs by flying-spot microdensitometry. 3. With [3H]proline as precursor, the grain densities were greater over surface epithelium than over submucosal gland. With [3H]glucose, grain densities were greater over the surface epithelium in three cases, equal in one and greater over submucosal gland in the last. [35S]Sulphate, given either into the tracheal segment or intravenously, yielded grain densities that were greater over the submucosal glands than over surface epithelium. 4. The areas of submucosal gland the surface epithelium were estimated by point counting and the total content of radioactivity in the two structures estimated by multiplying mean absorbance by area. Ratios of the total radiolabel in surface epithelium to that in submucosal gland were consistently high when [3H]proline was the precursor and low with [35S]sulphate, given by either route. [3H]Glucose gave intermediate ratios. 5. Secretions washed from the trachea were subjected to gel-exclusion chromatography. Washings from tracheas labelled with [3H]proline contained some molecules eluting in the void volume of a Sepharose CL-4B column (suggesting a relative molecular mass of greater than 10(6) Da), but more of the radiolabel eluted in three peaks in the partially included volume. Density gradient ultracentrifugation of the void volume material gave radiolabelled peaks at densities of approximately 1.60 and 1.50 g ml-1, consistent with glycosylated proteins, as well as less dense material (less than 1.30 g ml-1), probably proteins with little or no glycosylation. 6. We discuss the justification of using these radiolabelled precursors to give relatively selective labelling of secretory products from submucosal gland and surface epithelium. PMID- 2324984 TI - Vasodilatation of arterioles by acetylcholine released from single neurones in the guinea-pig submucosal plexus. AB - The nervous control of arterioles in the guinea-pig submucosal plexus was studied. Outside diameters of arterioles were recorded using a video-monitoring system. Changes in arteriolar diameter in response to electrical stimulation of single neurones or ganglia in the plexus were measured. 2. When the arteriole was pre-constricted with the prostaglandin analogue U46619 or with phenylephrine, electrical stimulation (2-20 Hz, 10 s) of a ganglion dilated the blood vessel. This vasodilatation was abolished by tetrodotoxin or by cutting the fine nerve strands running between the ganglion and the arteriole. 3. The vasodilatations caused by ganglionic stimulation were blocked by the muscarinic antagonists atropine, pirenzepine, (11[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11 dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-)-one (AFDX-116), 4 diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) and hexahydrosilodifenidol (HSDF). IC50 values for the inhibition of nerve-evoked vasodilatation by pirenzepine, AFDX-116 and HSDF were 500 nM, 4 microM and 25 nM respectively. Physostigmine (1 microM) increased the dilatation by 90%. 4. Muscarine dilated all submucosal arterioles; the concentration causing half maximum effects was 200 nM. Muscarinic vasodilatations were inhibited by pirenzepine, AFDX-116, and HSDF in a competitive manner; dissociation equilibrium constants determined by Schild analyses were 125 nM, 1.3 microM and 4 nM respectively. 5. Gossypol, an irreversible inhibitor of the production of endothelium-derived relaxing factor (EDRF), did not reduce the vasodilatation produced by either ganglionic stimulation or muscarine in submucosal arterioles. 6. Intracellular recordings were made from submucosal neurones and action potentials were elicited by depolarizing current pulses (10 ms duration, 10 Hz/10 s). In seven neurones vasodilatation was associated with intracellularly evoked action potentials; this vasodilatation was blocked by pirenzepine. Cell bodies of reidentified vasodilator neurones were subsequently shown to contain immunoreactive choline acetyltransferase. 7. These results show that cholinergic neurones in the submucosal plexus project to submucosal arterioles and that they release acetylcholine onto muscarinic receptors to produce vasodilatation. The muscarinic receptor activated by nerve-released acetylcholine is the M3 subtype and its location appears to be on the vascular smooth muscle rather than the endothelium. PMID- 2324985 TI - Cardiovascular and ventilatory responses to dynamic exercise during epidural anaesthesia in man. AB - 1. In order to evaluate the importance of afferent neural feedback from the working muscles for cardiovascular and ventilatory responses to dynamic exercise, epidural anaesthesia was induced at L3-L4. Six healthy males cycled for 20 min at 57% of maximum oxygen uptake and for 8-12 min at increasing work intensities until exhaustion at 238 +/- 30 W without as well as with epidural anaesthesia. 2. Presence of afferent neural blockade was verified by cutaneous sensory analgesia below T10-T11 and attenuated post-exercise ischaemic pressor response (45 +/- 8 24 +/- 6 mmHg). Efferent sympathetic nerves appear to be intact since basal heart rate and blood pressure as well as the cardiovascular responses to a Valsalva manoeuvre and to a cold pressor test were unchanged. 3. During dynamic exercise with epidural anaesthesia, blood pressure was lower than in control experiments; however, ventilation and heart rate were not affected. 4. The results indicate that afferent neural activity from the working muscles is important for blood pressure regulation during dynamic exercise in man but may not be necessary for eliciting the ventilatory and heart rate responses. PMID- 2324986 TI - Transport of calcium across the dually perfused placenta of the rat. AB - 1. A rat placenta was dually perfused in situ with modified Krebs fluid. Perfusion was carried out through the femoral artery on the maternal side and through the umbilical artery on the fetal side. 2. Transfer of 45Ca2+ and [3H]L glucose across the placenta was measured in the maternal-fetal direction. The transcellular component of the maternal-fetal transport of Ca2+, Jmf,tc, was estimated from transfer rates of the two tracers and from Ca2+ concentration in maternal perfusate, [Ca2+]m. 3. At [Ca2+]m of 1.1 mM (physiological concentration of Ca2+ in plasma) Jmf,tc was 92.4 +/- 13.7 nmol min-1 (mean +/- S.D.), which is about 90% of the transport expected in an intact placenta. The permeability surface area product (PS) of the placenta to [3H]L-glucose was 13.8 +/- 3.9 microliters min-1, about 4 times higher than that expected in intact placenta. 4. Transport of 45Ca2+ changed rapidly when [Ca2+]m was varied. Kinetic constants of the transcellular transport of Ca2+ are the Michaelis constant, Km, = 0.45 mM and the maximum rate of transport, Vmax, = 116 nmol min-1. It follows from this that at physiological levels of Ca2+, transport of Ca2+ to the fetus is relatively independent of changes in [Ca2+]m. 5. Strontium and barium (SrCl2 and BaCl2, 1 mM) decreased Jmf,tc; the response was prompt and reversible. Magnesium (2 mM) had no effect. Maternal-fetal transport of 85Sr2+ and 133Ba2+ was decreased rapidly and reversibly by elevating [Ca2+]m from 0.35 to 2 mM. These observations suggest that Sr2+ and Ba2+ are transported across the placenta by the Ca2+ transport system. This means that the transport is not substrate specific. 6. Cadmium (1 mM-CdCl2) decreased Jmf,tc irreversibly with some latency. The slowness of the response suggests a non-competitive inhibition. Cadmium (0.02 mM CdCl2) was without effect on Jmf,tc. 7. A Ca2+ channel blocker, nifedipine (10 microM), administered to the maternal side had no effect on Jmf,tc. PMID- 2324987 TI - Apical potassium channels in Amphiuma diluting segment: effect of barium. AB - 1. Single potassium channels have been studied in the apical membrane of isolated diluting segment tubules of Amphiuma using the patch clamp technique in the cell attached mode. A kinetic analysis of the interaction of the channel with barium is presented. 2. The channel shows inward rectification, with an inward conductance of 29.2 pS and an outward conductance of 7.5 pS (cell attached, 100 mM-KCl as pipette solution). 3. The channel is mildly voltage sensitive, the open probability of 0.8 at the resting membrane potential being reduced to 0.38 mV at a hyperpolarizing potential of 120 mV. The mean open time also decreased with hyperpolarization (from 51.3 to 11.6 ms at the above potentials). 4. Inclusion of barium in the pipette solution causes a concentration- and voltage-dependent block of the channel. The open probability was reduced by 40 and 79% of control with 0.1 and 1 mM-barium respectively (0 mV pipette potential). This inhibition increases to 70 and 95% at a pipette potential of 80 mV. 5. From the voltage dependence of the blockade by barium, it is estimated that barium ions block at a site one-third of the way across the membrane. 6. Given the high open probability of the channel at resting membrane potentials and the density of the channels on the apical surface of the cells it is concluded that the channels can account for the apical potassium conductance of the diluting segment of Amphiuma. PMID- 2324988 TI - Intracellular chloride activity in glial cells of the leech central nervous system. AB - 1. Chloride-sensitive double-barrelled microelectrodes were used to measure the intracellular Cl- activity (aicl) and membrane potential (Em) in neuropile glial cells of the leech, Hirudo medicinalis. 2. A close relation between the equilibrium potential for Cl- (ECl = -66.1 +/- 4.9 mV; mean +/- S.D.) and the resting potential (Em = -67.8 +/- 5.2 mV; n = 19) was observed in nominally CO2 HCO3(-)-free, HEPES-buffered solutions. A saline buffered with 2% CO2, 11 mM-HCO3 elicited a membrane hyperpolarization and a concomitant decrease of aCl. 3. Changes in ECl followed these of Em with a lag of less than 30 s in response to various extracellular K+ concentrations [( K+]o) or due to bath-application of carbachol or serotonin. 4. Introduction of a Cl(-)-free solution resulted in a transient depolarization indicating a substantial Cl- conductance and a rapid decrease of aiCl to an apparent value of 0.5-0.9 mM. 5. The loop diuretics furosemide (1 mM) and bumetanide (0.2 mM) did not affect the K(+)-induced changes of aiCl. 6. The results indicate a passive Cl- distribution across the membrane of leech neuropile glial cells as a result of a high Cl- conductance. PMID- 2324989 TI - Physiological properties of skinned fibres from normal and dystrophic (Duchenne) human muscle activated by Ca2+ and Sr2+. AB - 1. Contractile activation properties of various types of normal and dystrophic (Duchenne muscular dystrophy, DMD) human muscle fibres were investigated using mechanically skinned fibres activated in Ca2(+)- and Sr2(+)-buffered solutions at room temperature (21-25 degrees C). 2. The majority of the normal human muscle fibres (18/22; 82%) could be classified according to the Ca2(+)- and Sr2(+) activation characteristics in the same three major groups as other mammalian skeletal muscle fibres studied previously: slow-twitch (8/22; 36%), fast-twitch (3/22; 14%) and fast-twitch intermediate (7/22; 32%), which correspond to the three major histological fibre types I, II B and IIA respectively. 3. Of these three major groups only the slow-twitch (type I; 14/24; 58%) and the fast-twitch intermediate (type IIA; 3/24; 13%) fibres were found in the DMD muscle, indicating that fast-twitch fibres of type IIB were in very low proportion in DMD muscle. 4. The DMD muscle contained a new group of fibres (4/24; 17%) with different Ca2(+)- and Sr2(+)-activation characteristics from the three major histological types. This group of fibres is likely to be of embryonic type. 5. The maximum tension development ability of DMD fibres was less than 20% of that in normal fibres with the exception of some slow-twitch fibres which could produce near normal tension. 6. A significant proportion of normal (4/22; 18%) and DMD (3/24; 13%) fibres were found to have a mixture of Ca2(+)- and Sr2(+) activation characteristics. This can be explained by co-existence of various myofibrillar protein isoforms in different proportions with regulatory functions in the same individual fibre. 7. The results demonstrate that DMD leads to marked diminution in the ability of most individual skeletal muscle fibres to develop tension, and causes changes in the overall fibre-type distribution in afflicted muscles. PMID- 2324990 TI - A K+ channel in Xenopus nerve fibres selectively blocked by bee and snake toxins: binding and voltage-clamp experiments. AB - 1. The effects of mast cell degranulating peptide (MCDP), a toxin from the honey bee, and of dendrotoxin (DTX), a toxin from the green mamba snake, were studied in voltage-clamp experiments with myelinated nerve fibres of Xenopus. 2. MCDP and DTX blocked part of the K+ current. About 20% of the K+ current, however, was resistant to the toxins even in high concentrations. In Ringer solution half maximal block was reached with concentrations of 33 nM-MCDP and 11 nM-DTX. In high-K+ solution the potency of both toxins was lower. beta-Bungarotoxin (beta BuTX), another snake toxin, also blocked part of the K+ current, but was less potent than MCDP and DTX. 3. Tail currents in high-K+ solution were analysed and three K+ current components were separated according to Dubois (1981 b). Both MCDP and DTX selectively blocked a fast deactivating, slowly inactivating K+ current component which steeply activates between E = -60 mV and E = -40 mV (component f1). In concentrations around 100 nM, MCDP and DTX blocked neither the slow K+ current (component s) nor the fast deactivating, rapidly inactivating K+ current which activates between E = -40 mV and E = 20 mV (component f2). Similar results could be derived from K+ outward currents in Ringer solution. In high-K+, IC50 of MCDP for component f1 was 99 nM, whereas it was 7.6 microM for f2. Corresponding values for DTX are 68 nM and 1.8 microM. 4. Binding studies with nerve fibre membranes of Xenopus reveal high-affinity binding sites for 125I labelled DTX (KD = 22 pM in Ringer solution and 81 pM in high-K+ solution). 125I labelled DTX can be displaced from its sites completely by unlabelled DTX, toxin I (black mamba toxin), MCDP, and partially by beta-BuTX. 5. Immunocytochemical staining demonstrates that binding sites for DTX are present in nodal and paranodal regions of the axonal membrane. 6. The axonal membrane of motor and sensory nerve fibres is equipped with three types of well-characterized K+ channels and constitutes so far the best preparation to study MCDP- and DTX sensitive K+ channels with electrophysiological and biochemical methods. PMID- 2324991 TI - Evidence for the uptake of neuronally derived choline by glial cells in the leech central nervous system. AB - 1. With ion-sensitive microelectrodes based on the Corning exchanger 477317, the accumulation of an unidentified interfering substance was monitored in leech neuropile glial cells but not in neurons after a 10-fold increase in extracellular K+ concentration. Evidence is presented which shows that this substance may be choline. 2. The accumulation of interfering ions was not observed in Ca2(+)-free saline and was substantially reduced in the presence of eserine (a blocker of acetylcholinesterase). 3. In neuropile (and also packet) glial cells, extracellularly applied choline (10(-4) M) caused a steady increase in ion signal. This increase was not affected by removal of extracellular calcium, by hemicholinium-3 (a blocker of high-affinity choline uptake) or eserine. Shortly after the removal of choline from the saline the increase in ion signal stopped and the ion signal then decreased slowly to its original level. 4. Extracellular acetylcholine (10(-4) M) caused a similar increase in intracellular ion signal of neuropile glial cells to that caused by choline. This increase was blocked by eserine. 5. Extracellular choline caused a comparatively small increase in ion signal of Retzius neurones which was blocked by hemicholinium-3. In pressure neurones, choline or hemicholinium-3 had no effect on intracellular ion signal. 6. Autoradiographic analysis of [3H]choline uptake showed that most of the choline was taken up by glial cells in a time- and dose-dependent manner. Small but significant amounts of choline were taken up by neurones and connective tissue. 7. It is concluded that the neuropile and packet glial cells possess an effective choline uptake system which is activated by exogenous choline but also by choline that stems from enzymatic inactivation of acetylcholine released by neurones. PMID- 2324992 TI - Regulation of capillary blood flow and oxygen supply in skeletal muscle in dogs during hypoxaemia. AB - 1. Multiwire surface electrodes were used to measure local hydrogen clearance curves and tissue PO2 in vivo. Evaluation of the initial slopes of the hydrogen clearance curves enabled the measurement of capillary blood flow and its distribution. 2. Capillary blood flow and tissue PO2 frequency distribution histograms were measured in the m. sartorius of anaesthetized, relaxed mongrel dogs under conditions of normoxic (Fi, O2 = 0.3) and hypoxic (Fi, O2 = 0.15 and 0.1) artificial ventilation. 3. Stepwise hypoxaemia (hypoxic hypoxia) induced an increasing discrepancy between capillary blood flow and arterial blood flow. The former decreased by 6% whereas the latter increased by 86%. 4. PO2 histograms provided no evidence of cellular anoxia even at Fi,O2 = 0.1. Capillary blood flow histograms suggested a redistribution of the local pattern of flow. 5. A 34.7% reduction of O2 consumption was observed as the result of severe hypoxaemia. 6. The concept of heterogeneity of capillary blood flow as a functional O2 reserve is presented, together with evidence for oxygen-dependent regulation of capillary blood flow and oxygen consumption. PMID- 2324993 TI - Spatial patterns of reflex evoked by pressure stimulation of the foot pads in cats. AB - 1. The spatial patterns of reflexes elicited by localized pressure stimulation of the foot skin were analysed by recording electromyographic activities of various hindlimb muscles or muscle nerve discharges in cats anaesthetized with sodium pentobarbitone. 2. Reflex discharges evoked by stimulation of the central pad occurred mainly in physiological toe extensors located in the foot. Stimulus response relationships of single motor units revealed characteristically wide ranges of graded response and recruitment. 3. Within the central pad, the strongest excitation was evoked from the central lobe and was distributed to extensors of all four toes. Excitation from the medial and the lateral lobes was usually asymmetrical and weaker in toe muscles of the stimulated side. It is suggested that the weakness was in part due to concomitant inhibition. 4. Stimulation of a toe pad caused marked suppression of central pad-evoked activity of toe extensors with a highly specific spatial pattern. The inhibition was strongest in extensors of its own toe, and gradually weaker in the more distant toes. Weak excitation was occasionally evoked in extensors of the most medial or lateral toes, when the most lateral or the most medial toe-pad, respectively, was stimulated. 5. A similar pattern of relfex to that from the toe pad was evoked from the claw base and the hairy toe dorsum of each digit. 6. Reflex effects, both inhibitory and excitatory, from the central and toe pads, claw bases and toe dorsum were maintained during prolonged stimuli, indicating that slowly adapting receptors contributed to these reflexes. 7. It is concluded that stimulation of localized skin areas of the foot, particularly the pads, evokes highly specialized reflexes, which may be important in controlling movements of individual digits. PMID- 2324994 TI - Infrasound sensitive neurones in the pigeon cochlear ganglion. AB - The cochlear ganglion of the pigeon contains neurones sensitive to sound frequencies below 20 Hz (infrasound). They are characterized by a high spontaneous discharge rate (mean 115 imp/s). In contrast to ordinary auditory units, the mean discharge rate of these neurones is not increased by infrasound or sound stimuli, but modulated by these stimuli at levels comparable to the behavioural thresholds of pigeon reported by Kreithen and Quine (1979). PMID- 2324995 TI - Dioptrics of the facet lenses of male blowflies Calliphora and Chrysomyia. AB - 1. The dioptrics of the facet lenses of two blowfly species, Calliphora erythrocephala and Chrysomyia megacephala, was investigated. Measurements were performed on facet lenses ranging in diameter from 20 to 80 microns. 2. The radius of curvature of the front surface of the facet lenses, measured by microreflectometry, increases approximately linearly with the facet lens diameter. 3. The optical path difference of the facet lens and water, measured by interference microscopy, depends on the distance from the optical axis according to a parabolic function. Average refractive index values, calculated from the optical path difference profile together with estimates of the thickness profile, are between 1.40 and 1.43, with the lowest values in the largest lenses. 4. The F number calculated from the experimental data ranges from 1.5 to 2.2. It is argued that the range of effective F-numbers is 2.1-2.4. PMID- 2324996 TI - Auditory brain stem responses in characterization of dolphin hearing. AB - Auditory brain stem responses (ABR) were recorded from the head surface of non anesthetized and non-relaxed bottle-nosed dolphins, Tursiops truncatus. The region of best ABR recording was shown to be located 6-9 cm caudal to the blowhole. The threshold values were about 1 mPa for noise bursts and -3 dB re 1 mPa for tone bursts of the optimal frequency (80 kHz). The maximum frequency at which ABR could be evoked was 140 kHz. The duration of temporal summation reached 0.5 ms at intensities near the threshold and decreased with an increase in intensity. When the stimuli were paired clicks of the same intensity, the time to complete recovery from the second response was about 5 ms, while that to its 50% recovery was 0.7 ms. When the conditioning click exceeded the testing one in intensity, prolongation of the recovery period was observed. A 40-dB intensity difference led to an approximately 10-fold prolongation of this period. PMID- 2324997 TI - Eye movements in Daphnia magna. Regions of the eye are specialized for different behaviors. AB - Three types of behavior of the compound eye of Daphnia magna are characterized: 'flick', a transient rotation elicited by a brief flash of light; 'fixation', a maintained eye orientation in response to a stationary light stimulus of long duration; 'tracking', the smooth pursuit of a moving stimulus. The magnitudes of the flick and fixation responses vary with stimulus position and are generally proportional to stimulus intensity, although at high intensities there is an attenuation of both behaviors. When the stimulus is placed at a position approximately 80 degrees dorsal to the eye axis, there is no response; this area is called the null region. For stationary stimuli in other positions, the direction of the response is such as to bring the stimulus closer to the null region. During tracking, the relative positions of the eye and stimulus change; the eye velocity is approximately half that of the moving stimulus. The regions of the eye in which these behaviors may be induced are different, being largest for flick and smallest for tracking. It is proposed that flick and fixation responses are a means for rotating the eye so that the stimulus is within the area surrounding the null region which is used for tracking. PMID- 2324998 TI - Understanding hypertensives' behaviour. II: Perceived social approval and blood pressure reactivity. AB - The influence of perceived social approval on blood pressure reactivity was investigated in two stages. Initially, a new procedure was devised to measure the reaction to initial stimuli in subjects where base rate determination had not occurred. Minimal public self disclosure was shown to have a greater pressor effect for borderline hypertensives than normotensives. The two groups remained clearly distinguishable after exercise. Perceived level of social approval on physiological response in two groups of reactive borderline hypertensives was then investigated in the laboratory. Blood pressure level rose during an arithmetic task for all subjects. A large increase in blood pressure variability was specific to the self disclosure task and only for those who perceived low social approval. The ramifications are discussed. PMID- 2324999 TI - Type A behavior and exercise: a follow-up study of coronary patients. AB - Several previous studies have reported decreased Type A behavior pattern (TABP) after initiation of an exercise program. To determine if changes in TABP could be linked to exercise patterns in a cardiac rehabilitation program, both physical activity and TABP were measured in 81 male cardiac patients over a period of one year after hospitalization for an initial cardiac event. Changes in TABP scores were not associated with differences in activity patterns as measured by kilocalories per week of exercise, self-ratings of both job and leisure-time physical activity levels, or participation in a cardiac rehabilitation program. However, in Type A subjects there was a discrepancy between simple self-ratings of activity and more objective measures of exercise: subjects who had high TABP scores perceived themselves to be significantly more physically active than did subjects with lower TABP scores, even though the more objective estimates of physical activity were not associated with TABP scores. PMID- 2325000 TI - A procedure for reducing errors in reports of life events. AB - Despite the widespread use of life event inventories, relatively little research has been conducted evaluating whether recall techniques can reduce reporting errors. This study evaluated whether memory aids would reduce errors in reports of life events and explored subjects' explanations for why they had given inconsistent answers to life event questions over the course of two interviews. Seventy-one college students were randomly assigned to two groups: memory aids (MA: n = 36) and no memory aids (NMA: n = 35). Memory aids, as used in this study, reduced errors in reports of life events as reflected in the following results: (1) significantly fewer subjects in the MA group reported dating events incorrectly; (2) subjects in the MA group consistently gave more reliable responses between the two interviews as measured by intraclass correlations; (3) there was a significantly higher test-retest reliability correlation for life events reported by MA subjects; and, (4) MA subjects recalled more life events and had fewer inconsistent responses. A further probe revealed that memory aids differentially aided recall of subjective as compared to objective life events. Overall, the findings of this study suggest that memory aid procedures can differentially reduce errors in reporting life events. PMID- 2325001 TI - Life events and family history in children with recurrent abdominal pain. AB - Children suffering from recurrent abdominal pain (RAP) were compared with matched controls on measures of illness behaviour, parents' illness behaviour, early parent-child relationships and stressful life events. Relatively, the RAP children stayed away from school more, needed more attention when ill, tended to show more anxiety in various ways, had parents who reported more symptoms, and had suffered a greater number of stressful experiences in the few months before pain onset. PMID- 2325002 TI - A preliminary comparison of healthy elderly and young adults on the SUNYA Revision of the Psychosomatic Symptom Checklist. AB - Elderly (n = 30) and young (n = 30) subjects, equated in terms of general physical health, education and depression, were compared in terms of Total, Frequency and Intensity scores on the psychosomatic symptom checklist (PSC). Elderly subjects scored significantly lower than young subjects for both PSC Total and PSC Intensity scores. These results call into question the practice of aggregating PSC data from age heterogeneous samples and indicate the importance of reporting all three PSC scores. PMID- 2325003 TI - Psychosocial status at initiation of cancer treatment and survival. AB - Ninety-two newly diagnosed patients with hematologic malignancies treated with chemotherapy, and 47 patients with rectal cancer treated with abdominal-perineal resection were prospectively studied to assess the relationship between mood and survival. Hematology patients were measured within one week of diagnosis and were remeasured at six months. Rectal cancer patients were measured within three months of surgery and remeasured six months later. Medical records were abstracted to obtain data on treatment given, disease characteristics and outcome of treatment. On univariate analyses using Cox regression, we examined the effect of depression, coping style and locus of control on survival. None of these variables were found to be significantly related to survival whether assessed at intake or six months later. Furthermore there were no statistically significant correlations between these factors and subsequent survival at two years or with long-term survival. Biological prognostic variables including extent of disease for rectal cancer patients and severity of specific type of hematologic cancer were significantly related to survival. Although psychosocial adjustment is important for the quality of life experienced by cancer patients it was not related to length of survival in this study. Further exploration of this issue should be conducted using patients with a single site and preferrably an early stage of disease. PMID- 2325004 TI - Physical symptom cyclicity in women with and without the premenstrual syndrome. AB - A daily record of five physical symptoms was kept by 44 women self-selected as having the premenstrual syndrome (PMS+ group, 133 menstrual cycles) and 48 women self-selected as not having PMS (PMS- group, 100 cycles). Symptoms were analysed after fitting the first five terms of a Fourier series. PMS+ women differed significantly from PMS- women in (i) the incidence of significant physical symptom swings (present in 81.2% vs 33.0% of cycles), (ii) the incidence of significant physical symptoms in the premenstruum (PMT: present in 80.5% vs 24.0% of cycles), and (iii) PMT severity (mean +/- SE, 1.37 +/- 0.08 vs 0.27 +/- 0.04). Pregnanediol excretion and the distribution of stomach cramps were similar in the two groups. The small but significant symptom increase observed in the premenstruum of PMS-women is consistent with the view that premenstrual physical symptoms, unlike premenstrual psychological symptoms, may be associated with the normal menstrual cycle. For confirmation more evidence is required. PMID- 2325005 TI - Psychological factors in dyspepsia of unknown cause: a comparison with peptic ulcer disease. AB - Patients with dyspepsia of unknown origin (DUO) and those with similar upper abdominal symptoms but with an organic cause (peptic ulcer) were assessed on personality and psychological symptom measures. The DUO patients had significantly more symptoms of anxiety and tension and higher scores for trait tension and hostility than the organic group. The two groups did not differ significantly in terms of depressive symptoms, neuroticism, psychoticism, or suppression of negative affects. The implications of these findings for the aetiology and diagnosis of DUO are discussed. PMID- 2325006 TI - The construction and preliminary validation of a scale for measuring eating disorders. AB - The present paper reports on the construction and validation of a new scale for measuring eating disorders, the Eating Habits Questionnaire (EHQ), which is designed to assess not only existing disorders but also the likelihood of developing such disorders. The EHQ was initially validated on a large sample of university students, followed by further tests of reliability and validity amongst a number of both eating-disordered and normal comparison groups. Factor analysis of the initial item pool produced a 57-item, three-factor structure concerned with weight and dieting, restrained eating patterns, and overeating. Concurrent validation confirmed anticipated relationships with existing self report scales, and the EHQ was found to be both internally consistent and stable over time. The new scale distinguished reliably between diagnosed eating disordered patients and normal subjects, and results indicated that around 5% of undiagnosed female undergraduates scored in the same range as the patient population. PMID- 2325007 TI - [Upper cervical intradural lipoma. Apropos of a case]. AB - Intradural lipoma is a rare and slow growing tumor which represents 1% of all intra-spinal tumors. This tumor is often associated with dysraphism. It can be isolated without any associated vertebral or cutaneous malformations. Its clinical evolution is extremely slow and progressive. The fatty composition of this type of tumor allows easy detection by CT as well as by MRI. MRI permits: Reliable and direct assessment (in 3 different plans) of the extension of the lesion. An excellent post operative control. PMID- 2325009 TI - [Dosimetry in a controlled area]. PMID- 2325008 TI - [Moyamoya. Diagnosis using MRI and NMR angiography]. AB - A case of Moya-Moya disease confirmed by cerebral angiography in a 10-year-old girl is reported. Hypertrophic collateral circulation is easily visualized by MRI. MR angiography very accurately demonstrated the vascular obstruction and the collateral circulation. As MR angiography is not invasive, it promises to become a valuable alternative to conventional angiography in the diagnosis of Moya-Moya. PMID- 2325011 TI - Ultrastructural study of abnormal spermiogenesis in four hystricognate rodents. AB - Spermatids and epididymal spermatozoa from wild burrowing hystricognate rodents were examined. Structural defects affected the acrosome, the nucleus and the tail, and were similar to those found in the developing germ cells and spermatozoa from domestic mammals and man. The acrosome vesiculation of epididymal spermatozoa from hystricognate rodents might not be necessarily an abnormality and may represent a step in the acrosome reaction. Major abnormalities, such as invagination of the acrosome granule, incorporation of lytic vesicles into the forming acrosome, detachment of the acrosome from the flat surfaces of the nucleus, invagination of the nuclear envelope, and the occurrence of multinucleated and multitailed elements may be caused by a variety of factors, but those related to seasonal reproduction (breeding season) should not be neglected. PMID- 2325010 TI - [Measurement of the posterior wall of the intermediate bronchus. Diagnostic value]. AB - The posterior wall of the intermediate bronchial trunk (PWIB) is visible in most cases on profile thoracic radiographs. A retrospective study showed that it is thickened (over 3 mm) in cases of cardiac failure, right pneumonitis, adenopathy, right bronchopulmonary neoplasias and pulmonary fibrosis, either acute or chronic. The latter etiology had not yet been described in the literature. In our experience, assessment of the thickness of the intermediate bronchus provides a reliable criterium of response to treatment. The pathological mechanisms of intermediate bronchus thickening due to an increase of bronchial wall thickness or of peribronchial interstitial tissue are discussed. PMID- 2325012 TI - Plasma progesterone concentrations and length of the first spontaneous oestrous cycle in pubertal rats. AB - The length of the first spontaneous oestrous cycle in pubertal Wistar-Imamichi strain rats determined by vaginal smears varied from 5 to 18 days. The variation was ascribed to the period (3-16 days) of the stage of vaginal smears consisting of leucocytic cells (L stage). Plasma progesterone concentration and the decidual reaction in the uterus were used as indicators of the function of the corpus luteum and the L stage period was categorized as short, lasting for 3-6 days (average 4 days) with non-functional corpora lutea, or long, lasting 9-16 days (average 12 days) and with functional corpora lutea. Rats with the long L stage showed nocturnal and diurnal prolactin surges, but no daily changes in prolactin values were observed in rats with a short L stage. Daily changes in prolactin concentrations were maintained by the administration of progesterone in rats ovariectomized on Day 6 of the L stage. Plasma progesterone values on Day 6 of the L stage decreased with ergocornine treatment on Days 4 and 5 of the L stage and administration of bovine prolactin restored the level. These results indicate that the L stage observed in the first oestrous cycle is maintained by a positive feedback relation between progesterone and prolactin secretions. PMID- 2325013 TI - Platelet-activating factor and serum components from oestrous mice co-operate to mimic the activity of 'early pregnancy factor' in the rosette inhibition assay. AB - When male mouse spleen cells were incubated with a combination of platelet activating factor (PAF, 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) and sera from female mice in oestrus, the cells displayed a markedly increased rosette inhibition titre (RIT) when subsequently tested in the rosette inhibition assay. Neither PAF nor oestrous mouse sera alone could induce this effect, the combined action was required. Lyso-PAF could not substitute for the PAF, nor could male mouse sera nor the sera from females in dioestrus or metoestrus substitute for the oestrous mouse serum requirement. Pro-oestrous mouse sera could replace oestrous mouse sera but were less effective in their dose-responses. Studies on the mechanism of action of the PAF and oestrous mouse serum components suggested that the PAF stimulated the production and release of soluble factors (termed S2 factors) which by themselves could induce increased RIT values when applied to fresh spleen cells. The PAF-stimulated cell populations were rendered refractory to the action of these S2 factors and did not display increased RIT values, unless oestrous mouse serum was added. This serum acted to reverse the refractory state, allowing the S2 factors to exert their effect, and so cells treated with PAF and oestrous mouse serum displayed increased RIT values. PMID- 2325014 TI - Participation of ovarian 20 alpha-hydroxysteroid dehydrogenase in luteotrophic and luteolytic processes during rat pseudopregnancy. AB - In normal rats, before Day 12 of pseudopregnancy, minimal levels of 20 alpha-HSD activity were detected in functional CL whereas those in the residue were 3-5 times higher. When ovulation was blocked for more than 2 weeks by placing rats in a continuously lit environment before the induction of pseudopregnancy, only minimal levels of 20 alpha-HSD activity were detectable in the functional CL and residue before Day 12. In normal pseudopregnant rats, there was a linear increase in 20 alpha-HSD activity from Day 12 to 15 in the functional CL and residue, but the rate of elevation was much higher in functional CL. This tendency was much more clear-cut in rats in the continuous lighting. In immature rats in which pseudopregnancy was induced by PMSG and hCG treatment, 20 alpha-HSD activity peaked twice. The first small peak was attributed to the early regression of some of the large number of corpora lutea, and the changes in 20 alpha-HSD activity in most of the corpora lutea paralleled those in rats in continuous lighting. Bromocriptine abolished the prolactin surges, and in normal pseudopregnant rats an increase in 20 alpha-HSD activity in functional CL started from 12 h and the rate of the increase was accelerated from 36 h afterwards, while a relatively small increase was observed in the residue at 18 h and later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325015 TI - Serotonergic innervation of the rat testis. AB - The presence of 5-hydroxytryptamine (5-HT) was determined by h.p.l.c. in perchloric extracts of each isolated compartment of the adult rat testis. The testicular capsule, interstitial cells and interstitial fluid contained 5-HT, but 5-HT was not detected in the tubular compartment. In a group of adult rats, one testis was unilaterally denervated, and the contralateral testis used as control. The superior spermatic nerve, arising from the renal plexus, was excised and 1 week after surgery 5-HT content was measured in the capsule and interstitial fluid of both testes. Denervation caused a significant fall (34%) in 5-HT content. These results indicate that at least part of the testicular 5-HT derives from a serotonergic innervation of the gonad. PMID- 2325016 TI - The cycle of the seminiferous epithelium in the Japanese quail (Coturnix coturnix japonica) and estimation of its duration. AB - A regular, well defined spermatogenic cycle was found in the Japanese quail by examining thin sections of isolated lengths of seminiferous tubules embedded in epoxy resin to resolve the structure of developing spermatids. The stages of the cycle initially were identified in studies using a preparatory method for fixation which separated adjacent cellular associations. The cycle was divided into 10 stages with relative frequencies (%) of Stages I to X respectively of: 11.9, 14.8, 24.1, 10.3, 8.2, 6.4, 9.4, 5.5, 3.8 and 5.4. The duration of one cycle was 2.69 +/- 0.08 days (mean +/- s.e.m.) as determined by intraventricular injection of [3H]thymidine and autoradiographic examination of the testes 1-4 days later. It was estimated that lifespans were 2.01 days for type B spermatogonia, 3.86 days for primary spermatocytes, 0.15 days for secondary spermatocytes, and 4.54 days for spermatids. The results suggest that the kinetics of spermatogenesis in the quail are fundamentally similar to the pattern in mammals. PMID- 2325017 TI - Endocrine changes during pregnancy, parturition and the early post-partum period in the llama (Lama glama). AB - Mean (+/- s.d.) pregnancy length for the 14 llamas in this study was 350 +/- 4.5 days. Plasma progesterone concentrations increased by 5 days after mating and remained elevated (greater than 2.0 ng/ml) throughout most of pregnancy. At about 2 weeks before parturition, plasma progesterone concentrations began to decline, dropped markedly during the final 24 h before parturition, and returned to basal concentrations (less than 0.5 ng/ml) by the day of parturition. The combined oestrone + oestradiol-17 beta and oestradiol-17 beta concentrations varied between 6 and 274 pg/ml and 4 and 114 pg/ml, respectively, during the first 9 months of pregnancy. Concentrations increased between 9 months after mating and the end of pregnancy with peak mean concentrations of 827 +/- 58 (s.e.m.) pg oestrone + oestradiol-17 beta/ml (range: 64-1658) and 196 +/- 10 pg oestradiol-17 beta/ml (31-294) during the last week of pregnancy. Concentrations then declined to 87 +/- 14 pg oestrone + oestradiol-17 beta/ml (7-488) and 25 +/- 5 pg oestradiol-17 beta/ml (2.5-142) during the first week post partum. Plasma cortisol concentrations varied between 2.6 and 51.9 ng/ml (14.0 +/- 0.5) from mating until 2 weeks before parturition when the concentrations began to decline. Only a slight increase in plasma cortisol concentrations was observed in association with parturition. Plasma triiodothyronine concentrations varied between 0.5 and 4.5 ng/ml (1.9 +/- 0.1) throughout pregnancy and the periparturient period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325018 TI - Reproductive anatomy, manipulation of ovarian activity and non-surgical embryo recovery in suni (Neotragus moschatus zuluensis). AB - Marked disparity in the uterine horn dimensions and relative degrees of caruncle development in suni suggested that exclusive or predominant dextral implantation occurs in association with bilateral ovulatory activity. Daily urinary measurements of pregnanediol-3 alpha-glucuronide revealed an oestrous cycle of approximately 21 days in length. Ovarian activity was controlled for synchronization of oestrus by using progestagen-impregnated intravaginal sponges and multiple ovulations were induced by using exogenous gonadotrophin therapy. An effective transcervical uterine catheterization technique was developed for the non-surgical collection of embryos. The efficiency of embryo recovery performed 5 days after sponge removal was 50.0%. PMID- 2325019 TI - Social suppression of ovarian cyclicity in captive and wild colonies of naked mole-rats, Heterocephalus glaber. AB - To investigate the endocrine cause of reproductive suppression in nonbreeding female naked mole-rats, animals from 35 colonies were studied in captivity. Urinary and plasma progesterone concentrations were elevated in pregnant females (urine: 10.0-148.4 ng/mg Cr, 27 samples from 8 females; plasma: 3.6-30.0 ng/ml, 5 samples from 5 females; Days 21-40 of pregnancy) and cyclic breeding females (urine: 0.5-97.8 ng/mg Cr, 146 samples from 7 females; plasma: less than 1.0-35.4 ng/ml, 25 samples from 7 females). The latter group showed cyclic patterns of urinary progesterone, indicating a mean ovarian cycle length of 34.4 +/- 1.6 days (mean +/- s.e.m.) with a follicular phase of 6.0 +/- 0.6 days and a luteal phase of 27.5 +/- 1.3 days (19 cycles from 9 breeding females). In non-breeding females urinary and plasma progesterone values were undetectable (urine: less than 0.5 ng/mg Cr, 232 samples from 64 females; plasma: less than 1.0 ng/ml, 7 samples from 6 females). Breeding females had higher (P less than 0.001) plasma LH concentrations (3.0 +/- 0.2 mi.u./ml, 73 samples from 24 females) than did non breeding females (1.6 +/- 0.1 mi.u./ml, 57 samples from 44 females). Urinary and plasma progesterone concentrations in non-breeding females from wild colonies situated near Mtito Andei, Kenya, were either below the assay sensitivity limit (urine: less than 0.5 ng/mg Cr, 11 females from 2 colonies; plasma: less than 1.0 ng/ml, 25 females from 4 colonies), or very low (plasma: 1.6 +/- 0.6 ng/ml, 15 females from 4 colonies). In captivity, non-breeding females removed from their colonies (i.e. the dominant breeding female) and either paired directly with a non-breeding male (N = 2), or removed and housed singly for 6 weeks before pairing with a non-breeding male (N = 5) may develop a perforate vagina for the first time in as little as 7 days. Urinary progesterone concentrations rose above 2.0 ng/mg Cr (indicative of a luteal phase) for the first time 8.0 +/- 1.9 days after being separated. These results suggest that ovulation is suppressed in subordinate non-breeding female naked mole-rats in captive and wild colonies, and show that plasma LH concentrations are significantly lower in these non-breeding females. This reproductive block in non-breeding females is readily reversible if the social factors suppressing reproduction are removed. PMID- 2325020 TI - Influence of daylength on the initiation of the breeding season of the marsupial possum, Trichosurus vulpecula. AB - In Queensland, possums in the wild and in captivity first give birth during March and continue to give birth throughout the year until November. In this study the effect of short daylengths on the initiation of breeding activity was examined. One male and 4 female possums were transferred from an outside enclosure into a light control room (10 h light, 14 h dark) on 22 November. A control group of possums was housed in outside enclosures. The possums held in the light room gave birth 81.2 +/- 14.7 days (s.e.m.) after being placed in the short-day photoperiod. The control group gave birth 133.8 +/- 9.8 days after 22 November. This result suggests that photoperiod plays a role in the initiation of the breeding season of the brushtail possum. PMID- 2325021 TI - Expression of capacitation-dependent changes in chlortetracycline fluorescence patterns in mouse spermatozoa requires a suitable glycolysable substrate. AB - Chlortetracycline (CTC) fluorescence patterns were assessed in epididymal mouse sperm suspensions capacitated in exogenous substrate-containing and substrate free media. A capacitation-dependent transition from a majority of acrosome intact cells expressing the uncapacitated F pattern of fluorescence to a majority with the capacitated acrosome-intact B and acrosome-reacted AR patterns was confirmed for suspensions incubated a total of 120 min in the presence of a glycolysable substrate, glucose. In contrast, assessment of spermatozoa incubated for 120 min in substrate-free medium revealed a majority of cells with the uncapacitated F pattern, despite an earlier demonstration that such cells are essentially capacitated: upon the introduction of glucose, suspensions are immediately highly fertile. When a suitable glycolysable substrate, either glucose or mannose but not fructose, was added to such suspensions, the distribution of CTC patterns changed within 10 min to a majority of B and AR patterns. Furthermore, the degree of change from uncapacitated to capacitated patterns was substrate concentration-dependent. In contrast, the introduction of the non-metabolizable substrates 2-deoxyglucose and 3-0-methylglucose and the oxidizable substrates sodium pyruvate and sodium lactate caused no change in the patterns from those seen in substrate-free medium. The in-vitro fertilizing ability of sperm suspensions to which increasing amounts of glucose or mannose were added, after initial substrate-free preincubation, directly paralleled the changes in CTC patterns and was as rapid as for suspensions incubated continuously in either hexose. We therefore conclude that the alteration in position of surface components to which CTC binds is not only capacitation dependent, but also energy-dependent. In the absence of an appropriate exogenous glycolysable substrate, the final transition cannot occur, even though the cells are essentially capacitated. PMID- 2325022 TI - Sustained reproductive responses in Djungarian hamsters (Phodopus sungorus) exposed to a single long day. AB - Male and female Djungarian hamsters maintained from birth in a short photoperiod (8 h light per day; 8L:16D) showed substantial testicular and uterine growth in response to a single long photoperiod or a 15-min light pulse that interrupted the 16-h dark period at 18 days of age. These light regimens resulted in heavier testes and uteri at 30 and 35 days of age when compared with those of control animals. Similar results were obtained in hamsters maintained from birth to Day 18 in a long photoperiod (16L:8D), given a single longer day (20L:4D) or constant light on Day 18 and then transferred to a short photoperiod (8L:16D) on Day 19. At 35 days of age animals that received extended light treatment on Day 18 had significantly more developed reproductive structures than did control hamsters. The marked effects of brief light treatment in producing long-term changes in the reproductive axis provide a convenient mammalian model system in which to study neuroendocrine events that underlie photoperiodism. PMID- 2325023 TI - Control of first cleavage in single-cell reconstituted mouse embryos. AB - Karyoplasts derived from mouse embryos at the initial and final stages of the first or second mitotic interphase were fused to early and late enucleated 1-cell embryos. The time of cleavage of reconstituted and control embryos was recorded at 1-h or 8-h intervals after manipulation. This enabled assessment of nuclear and cytoplasmic control over the mitotic apparatus of the 1-cell embryo. Early nuclei from 1- or 2-cell embryos fused to late enucleated embryos delayed cleavage but for only a few hours. However, late nuclei fused to early enucleated embryos were unable to advance the cytoplasmic timing of the next cleavage division. Furthermore, these reconstituted embryos stayed in interphase longer than did controls and many embryos with nuclei derived from late 2-cell embryos failed to cleave. These findings suggest that, allowing for a short period, early nuclei can synchronize with late cytoplasm with no major damage to the cleavage apparatus. It is proposed that this period is required for the completion of DNA synthesis by the early nuclei. However, late nuclei cannot induce mitosis before the expected cytoplasmic time, and, with 2-cell karyoplasts, this interaction causes many embryos to 'block' in interphase, without cleaving, suggesting incompatible nucleo-cytoplasmic interactions between late 2-cell karyoplast and early 1-cell stage cytoplasm. PMID- 2325024 TI - Effect of the human cumulus oophorus on movement characteristics of human capacitated spermatozoa. AB - The effect of human cumulus oophorus on movement characteristics of human spermatozoa previously incubated in vitro under capacitating conditions was studied using automated digital image analysis. When spermatozoa were incubated for a short time with whole cumuli, most of those that penetrated the cumulus intercellular matrix were characterized by a linear movement with small amplitudes of lateral head displacement, but with elevated values of beat cross frequency. Short (5 min) incubation with solubilized cumulus intercellular matrix of spermatozoa preincubated in capacitating conditions (6 h) significantly reduced the percentage of spermatozoa showing the 'hyperactivated' type of motility characterized by high curvilinear velocity, low progressive velocity and elevated values of lateral head displacement. Moreover, a subpopulation of spermatozoa with very high values of progressive velocity and beat cross frequency and with reduced amplitudes of lateral head displacement appeared in these conditions. This cumulus-related motility pattern was not seen in fresh spermatozoa or in those incubated in the absence of cumulus material. Changes in the sperm movement characteristics similar to those observed in the presence of the solubilized cumulus matrix could also be induced by some of its h.p.l.c. fractions. These results show that the intercellular matrix of the human cumulus oophorus exerts a specific effect on human sperm motility, probably acting preferentially on the 'hyperactivated' sperm subpopulation. PMID- 2325025 TI - Expression of the gene for anti-Mullerian hormone. AB - The expression of anti-Mullerian hormone, also called Mullerian-inhibiting substance or factor, is limited to immature Sertoli and post-natal granulosa cells. To gain information on the genetic mechanisms of this tissue- and development-specific regulation, a human genomic clone containing 3.6 kilobases of 5' flanking sequences has been isolated and sequenced. Transcription initiation sites include a major site, at the same position as in the bovine gene, and 3 minor sites, accounting together for 12% of transcripts. Sequences of potential interest include an Sp1 binding site, minisatellite-like regions, and a 13-base pair palindrome, nearly identical to the oestrogen response element of the vitellogenin genes. This palindrome binds to the human oestrogen receptor in vitro and activates transcription of a hybrid gene when several copies are inserted 5' of a thymidine kinase promoter. Further studies are needed to determine whether this palindrome is implicated in a feed-back loop regulating oestrogen synthesis in granulosa cells. PMID- 2325026 TI - Gene expression in the mammary gland. AB - We have demonstrated that the ovine genomic clone SS1 can be used to generate transgenic mice that produce significant quantities of BLG protein in milk. The smallest BLG construct so far examined that retains the ability to direct BLG to mouse milk encompasses approximately 7.3 kb of genomic DNA, of which about 0.8 kb is derived from the promoter region. Gene expression is tissue-specific and regulated in a temporal and developmental fashion that is similar to that reported for sheep. We conclude, therefore, that the cis-acting sequences determining mammary expression of the ovine BLG gene are correctly interpreted in mice, despite the absence of an equivalent gene in this species, and that conclusions drawn from future work on BLG expression in the mammary gland of transgenic mice will be broadly applicable in sheep and other ruminant species. Work is currently in progress to define other sequences within the promoter of BLG that are required for regulated expression in transgenic mice. These and other studies into the DNA-protein interactions within the promoter which are required for efficient tissue-specific, regulated expression should lead to a greater understanding of milk protein gene expression in the mammary gland. Furthermore, in the current absence of a suitable in-vitro system, the mouse will be most useful for evaluating the expression of further constructs designed to express foreign proteins in milk of domestic ruminants. PMID- 2325027 TI - Mechanisms of action of steroid receptors in the regulation of gene transcription. AB - Steroid hormones regulate rates of transcription of certain genes by binding as a hormone-receptor complex to specific DNA sequences termed steroid-response elements. These elements consist of inverted repeats of the sequence TGTTCT for glucocorticoids, progestagens and androgens and TGACC for oestrogens. Domains for steroid binding, DNA binding and transcriptional activation have been defined in the mouse oestrogen receptor. PMID- 2325028 TI - Implications of sampling the implantation site in the endometrial biopsy for infertility. AB - Endometrial sampling performed during the cycle of conception occurs uncommonly. Less frequent is inclusion of the implantation site in an endometrial specimen obtained late in the luteal phase during the course of an infertility evaluation. From 1984 to 1987 the implantation site was sampled in 3 of 520 (0.6%) endometrial biopsies for infertility. In each instance the pregnancy did not continue. Two women conceived again within a year; both delivered term infants. The third woman had not conceived after ten months of follow-up. When an infertility biopsy results in a diagnosis of intrauterine pregnancy, further evaluation of the patient should be determined by the clinical situation: even in couples with extremely compromised fertility the woman occasionally will become pregnant. The prognosis for that pregnancy may be poor; however, the prognosis for subsequently conceiving and carrying a pregnancy to term is encouraging. This study demonstrated the relative safety of endometrial sampling in the infertile woman. The use of barrier contraception during the cycle of sampling can further decrease the chance of interrupting an intrauterine pregnancy. PMID- 2325029 TI - Cefotaxime for cesarean section prophylaxis in labor. Intravenous administration vs. lavage. AB - To compare the efficacy of antibiotic prophylaxis through uterine lavage in women undergoing cesarean section in labor to the efficacy of the more standard, perioperative intravenous method, we prospectively randomized 100 women to receive either 2 g of cefotaxime in 1,000 mL of normal saline with a lavage protocol or 1 g of cefotaxime intravenously after cord clamping followed by 1-g doses 6 and 12 hours later. The two groups were similar with respect to age, gestational age, race, weight, length of labor and of ruptured membranes, use of internal monitoring, blood loss and number of vaginal examinations. Standard febrile morbidity and postpartum endomyometritis requiring antibiotic therapy occurred in 18% and 12%, respectively, of the lavage group and in 16% and 12%, respectively, of the intravenous group. Before the routine use of prophylactic antibiotics for cesarean section in labor on our service, the febrile morbidity and endomyometritis rates were 36% and 32%, respectively. The results confirm the benefit of prophylactic antibiotics for cesarean section in labor and demonstrate that the lavage and intravenous methods are similar with respect to efficacy. PMID- 2325030 TI - Lamicel for induction of labor. AB - Lamicel is a synthetic osmotic cervical dilator currently used as a method of cervical dilation in first- and second-trimester pregnancy termination. It works by extracting fluid from the cervical tissue and softening the cervix. This study evaluated its effectiveness in nonelective medical induction of labor in high risk patients. Forty inpatients who, for medical and obstetric reasons, required delivery within the next 24-48 hours were studied. Patients were evaluated to make certain that a 12- to 24-hour delay was safe for mother and child. The evening prior to the day of induction, a pelvic examination determined the Bishop score, and bacterial cultures were obtained from the endocervix. As many Lamicels as possible (usually one to three) were then placed in the endocervix without rupturing the membranes. The next morning the devices were removed, a repeat Bishop score obtained, amniotomy performed, internal monitors placed and oxytocin infusion initiated. Data were collected for preinsertion and postinsertion Bishop scores, induction-delivery times, duration of ruptured membranes, and cesarean and vaginal birth rates. Maternal and neonatal infectious morbidity was determined. A comparison group of patients with premature rupture of the membranes was selected. From data studied at our institution, patients were matched for parity and duration of labor (not significantly different from the Lamicel group). The study revealed that Lamicel can be an effective means of ripening the cervix for induction of labor. PMID- 2325032 TI - Perinatal outcome after a prolonged second stage of labor. AB - It is commonly held that the second stage of labor should last no more than two hours because of an apparently increased risk of morbidity. The purpose of this investigation was to determine whether this commonly held notion is true in this era of close fetal monitoring and umbilical blood gas determination. Between May 1987 and October 1988, 50 (3.5%) of 1,432 uncomplicated term pregnancies ended in delivery after a second stage of labor lasting greater than 120 minutes. A prolonged second stage was associated more commonly with nulliparity, occiput posterior positioning, epidural anesthesia and a need for operative delivery but not birth weight greater than 4,000 g or a short umbilical cord. Infants born after a prolonged second stage did not have an increased incidence of umbilical artery pH less than 7.20 or of five-minute Apgar scores less than 7, nor did they need intensive care nursery admission. A prolonged second stage of labor appears not to impose an increased hazard on the fetus but does require close fetal monitoring and increases the possibility of operative delivery. PMID- 2325031 TI - Ultrastructural basis for continued steroidogenesis in the rat polycystic ovary. AB - Because constant light causes persistent estrus in the rat, that animal provides a suitable experimental model for studying the pathogenesis of polycystic ovary disease. We studied the scanning and transmission electron microscopic features of the rat polycystic ovary along with changes in serum estradiol and progesterone concentrations to further elucidate the mechanism of chronic anovulation during persistent estrus. The surface epithelium of the polycystic ovary showed no ovulatory stigmas and contained focal areas of degenerating and proliferating cells. The tunica albuginea was conspicuous, with many fibrils, collagenous materials and fibroblastlike cells adjoining the theca externa layer. The cytoplasm of theca interna cells contained numerous lipid vacuoles and images of extracted cholesterol crystals. The granulosa cells were atrophic and lacked the prominent Golgi apparatus typically found in granulosa cells of proestrous ovaries in cycling rats. With an increasing duration of constant light and chronic anovulation, the mean serum estradiol concentration in persistent-estrus rats was significantly higher and the mean serum progesterone concentration significantly lower than in age-matched controls. Alterations in estradiol progesterone metabolism in the ovaries may be important etiologic factors in the pathogenesis of chronic anovulation found in polycystic ovary disease in rats. PMID- 2325033 TI - The gynecologist's role in the treatment of breast carcinoma. AB - The treatment of early carcinoma of the breast remains contraversial. One hundred eleven cases of stage I and II carcinoma of the breast treated from January 1985 to November 1988 were reviewed. Given an informed choice, 13 of the 30 patients (43.3%) treated by the author chose breast conservation over mastectomy, in striking contrast to a 97.5% incidence of mastectomy in the 81 patients treated by the general surgeons on the hospital staff. The role of the gynecologist in the treatment of breast cancer can be to offer a different viewpoint and thus possibly to become a major force in the reduction in the number of mastectomies. PMID- 2325034 TI - Amniotic fluid interleukin-1 in spontaneous labor at term. AB - The regulatory signals responsible for the increased biosynthesis of prostaglandins during parturition have not been established. Interleukin-1 (IL-1) is capable of stimulating prostaglandin production by intrauterine tissues and is an inflammation mediator. It has been postulated as a signal for the onset of labor in the setting of intrauterine infection. A study was designed to determine if spontaneous labor at term was associated with changes in IL-1 activity in amniotic fluid. Such fluid was retrieved from 41 women in labor and from 39 women who were not in labor at term. Immunodetectable IL-1 beta was present in 22 of the 41 women in labor but in only 8 of the 39 women without labor. IL-1-like bioactivity was not different between the two groups at a dilution of 1:4, but at dilutions of 1:12, 1:36 and 1:108, amniotic fluid from women in labor had significantly higher bioactivity than that from women not in labor. A significant correlation was found between the bioassay and immunoassay results. Our data show that inhibitors of IL-1 bioactivity are present in amniotic fluid and suggest that in a subset of laboring women at term, an inflammatory reaction may play a role in triggering the onset of parturition. PMID- 2325035 TI - Relationship of early intrapartum fetal heart rate patterns to subsequent patterns and fetal outcome. AB - This study evaluated subsequent fetal heart rate (FHR) patterns and fetal outcome in laboring women with normal or abnormal initial FHR patterns. Four hundred term gravidas presenting in the latent phase of labor were studied. Ninety (22.5%) exhibited abnormalities on the initial tracing, with the majority of those abnormalities (58.9%) including mild variable decelerations, either alone or in combination with other abnormalities. An analysis of the outcome for those patients revealed a significant increase in cesarean delivery for fetal distress and depressed one-minute Apgar scores when compared to patients with initially normal tracings. Analysis of subsequent FHR patterns in that group showed a significant increase in the incidence of atypical variable declerations and bradycardia. Patients with more than one abnormality on the initial FHR tracing showed a greater incidence of loss of variability, loss of reactivity and bradycardia on subsequent FHR tracings. Likewise, pregnancy outcome for this group was remarkable for an increased risk of meconium staining, cesarean delivery for fetal distress and depressed one-minute Apgar scores. An abnormal initial FHR tracing seems to be associated with the subsequent development of ominous FHR patterns and increased fetal morbidity, particularly when more than one abnormality is present on the initial tracing. PMID- 2325036 TI - Safety of outpatient cerclage. AB - One hundred one women who underwent scheduled McDonald cerclage were studied. Fifty outpatients were reviewed prospectively, and 51 inpatients were studied retrospectively and concurrently. Forty-five outpatients and 48 inpatients completed pregnancy. The fetal outcomes were similar for both groups, with no significant differences in the number of complications for newborn infants. The average cost of the procedure (exclusive of physician fees) for outpatient cerclage was $546 and for inpatient, $1,174. The difference clearly shows the cost-effectiveness of outpatient cerclage. PMID- 2325037 TI - Intrapartum fetal vibratory acoustic stimulation during spontaneous and induced states of low activity and low heart rate variability. AB - Fetal response to vibratory acoustic stimulation (VAS) was studied in 12 healthy parturients in the active phase of labor. All fetuses were evaluated in both spontaneous and analgesia-induced states of low activity and low cardiac beat-to beat variability. Analgesia was induced with intravenous maternal administration of meperidine, 0.8 mg/kg, plus a fixed dose of promethazine (25 mg). The vibratory acoustic stimulus was applied ten minutes after the start of a fetal quiet state, and ten minutes of fetal behavior was observed after application of the stimulus. The number and mean duration of fetal body movements in the unmedicated fetuses were statistically significantly higher than in the medicated group. Similarly, the number of fetal heart rate accelerations was significantly higher in the unmedicated fetuses than in the medicated ones. Ten minutes after VAS no fetus in the unmedicated group was in a quiet behavioral state, while 10 of 12 medicated fetuses (83%) returned to a quiet state. PMID- 2325038 TI - Cervical intraepithelial neoplasia. The role of age at first coitus in its etiology. AB - A case-control study was done on 115 women attending a colposcopy clinic. All the patients had definitive histologic confirmation of cervical intraepithelial neoplasia (CIN). A specially designed questionnaire sought information about their age, age at first coitus, gravidity, ethnic origin, religion and social class. Cases and controls were closely matched for age and the last three parameters mentioned above. There was no statistical difference between nulliparas and multiparas in the incidence of CIN. The time interval between age at first coitus and the diagnosis of CIN varied widely, with 47 years the maximum. Statistically significant differences existed between the age at first coitus for cases and controls under and over age 18. The estimated relative risk was 3.64-fold higher in those under 18 than in those 18 or over at first coitus. PMID- 2325039 TI - Chromic gut pelviscopic loop ligature. Effect of the number of pulls on the tensile strength. AB - The failure load of a pelviscopic loop ligature (PLL) was determined after tightening the slip knot with one, two or three pulls. The PLL showed a significant decrease in strength when tightened with three or more pulls. In each group some PLLs failed from slippage rather than from fracture of the suture material at the base of the knot. Slippage occurred more frequently with each additional pull. The findings indicate that the surgeon should apply only one pull on the device for the most secure knot. In addition, there was no strength difference between the suture material itself and the junction of the suture and its plastic tail grip. The plastic tail grip of the PLL will not release the tail end of the suture material before either the suture material or the slip knot fails. PMID- 2325040 TI - Premature rupture of the membranes in a single twin gestational sac. A case report. AB - Premature rupture of the membranes was diagnosed with ultrasound and subsequent injection of dye into the upper sac of a 15-week twin gestation. Because of a history of prolonged infertility, conservative treatment (including bed rest, antibiotics and intravaginal povidone-iodine pessaries) was given. Four weeks later the leakage of amniotic fluid stopped, and at 32 gestational weeks the patient delivered healthy twins by cesarean section. No sign of chorioamnionitis was noted clinically or histologically. It seems that in this unusual case the lower sac was acting as a tampon and at some stage prevented further escape of amniotic fluid as well as ascending infection. PMID- 2325042 TI - Supernumerary ovary. A case report. PMID- 2325041 TI - Typhoid fever in pregnancy. A case report. AB - A pregnant woman was treated for typhoid fever. A consideration of geographic risks and serologic clues helped determine the diagnosis. PMID- 2325043 TI - Pelvic ganglioneuroma during pregnancy. A case report. AB - Ganglioneuroma of the pelvis occurred in a pregnant woman. The tumor arose from the sympathetic chain. Obstruction of a vaginal delivery was considered likely, and cesarean delivery was elected. This is the first report of this tumor in pregnancy. Management of such tumors in women who desire further childbearing should be conservative due to the low malignant potential and slow growth of the neoplasm. On completion of childbearing, excision is the treatment of choice. PMID- 2325044 TI - Status epilepticus in pregnancy. A case report. AB - A 34-year-old woman, epileptic since childhood, was admitted during the 26th-27th week of her second pregnancy because of status epilepticus. Effective treatment of the seizures allowed the pregnancy to reach term, and a healthy infant was born. A conservative treatment regimen involving seizure control and preservation of pregnancy is recommended. PMID- 2325045 TI - Fetal ventricular tachycardia associated with nonimmunologic hydrops fetalis. A case report. AB - A very rare case occurred of fetal ventricular tachycardia associated with nonimmunologic hydrops fetalis and diagnosed on echocardiography. Attempted cardioversion with quinidine was unsuccessful. PMID- 2325046 TI - Solitary metastasis of renal adenocarcinoma to the vagina. A case report. AB - Solitary metastases are not unusual in renal adenocarcinomas. Vaginal metastases occur but rarely and are the cause of presentation in most patients. Because of the tumor's similarity to other primary gynecologic tumors, the patients present difficult diagnostic and management problems, as shown by the case reported here. PMID- 2325047 TI - Neonatal Streptococcus pneumoniae septicemia and meningitis. A case report. AB - Neonatal septicemia/meningitis from Streptococcus pneumoniae occurred in a 36 hour-old infant. The mother had no overt evidence of infection. This case illustrates the pathogenic potential of this common bacterium in the neonate. PMID- 2325048 TI - Mullerian dysgenesis associated with a chromosomal anomaly and mental retardation. A case report. AB - A 26-year-old woman with mental retardation and a known chromosomal anomaly (46XX[13 p+]) was found to have mullerian agenesis. This is the first reported case of a mullerian anomaly and an autosomal chromosomal abnormality. PMID- 2325049 TI - Vaginal dilators for intermittent pelvic support. A case report. PMID- 2325050 TI - New standards in arthritis care. Proceedings of an ILAR symposium. Rio de Janeiro, Brazil, September 18, 1989. PMID- 2325051 TI - Identification of patients at risk for gastropathy associated with NSAID use. AB - It is suggested that gastropathy associated with nonsteroidal antiinflammatory drugs (NSAID) is the most frequent and, in aggregate, the most severe drug side effect in the United States. This work is based on a consecutive series of 2,400 patients with rheumatoid arthritis (RA) followed prospectively for an average of 3.5 years by the American Rheumatism Association Medical Information System. We present a preliminary exploration of the magnitude of the problem, the population at risk and the patients within that population who are at particularly high risk. Patients on NSAID had a hazard ratio for gastrointestinal (GI) hospitalization that was 6.45 times that of patients not on NSAID. Characteristically, patients at high risk for GI hospitalization and GI death are older, have had previous upper abdominal pain, have previously stopped NSAID due to GI side effects and have previously used antacids or histamine2-receptor antagonists for GI side effects. These patients also frequently take corticosteroids. Patients attributing relatively minor symptoms to NSAID tend to be younger and female. Our preliminary analysis is univariate; since these variables are interdependent, firm conclusions regarding the relative importance of these risk factors require development of multivariate risk factor models. The syndrome of NSAID-associated gastropathy can be estimated to account for at least 2,600 deaths and 20,000 hospitalizations each year in patients with RA alone. PMID- 2325052 TI - Effects of oral prostaglandins on indomethacin-induced renal failure in patients with cirrhosis and ascites. AB - Nonsteroidal antiinflammatory drugs (NSAID), such as indomethacin, reduce production of renal prostaglandins and markedly impair renal function in patients with cirrhosis and ascites. To determine if simultaneous administration of oral prostaglandin analogs minimizes the renal impairment, 10 patients received indomethacin and either misoprostol or placebo in a double-blind, crossover study. Indomethacin reduced urinary sodium from 23 +/- 9 to 8 +/- 4 microEq/min in 4 hours. Misoprostol with indomethacin tended to prevent the fall in urinary sodium (from 35 +/- 15 to 46 +/- 21 microEq/min at 4 hours), but sodium excretion fell to the same level in both groups by 8 hours (6 +/- 3 microEq/min). Indomethacin reduced creatinine clearance in 4 hours by 49%; misoprostol plus indomethacin reduced creatinine clearance by only 34%. Misoprostol tended to minimize or delay the nephrotoxic effects of indomethacin, suggesting that more potent prostaglandin analogs may prevent the renal impairment induced by NSAID. PMID- 2325053 TI - Coronary heart disease: when should prevention start? PMID- 2325054 TI - Open access exercise electrocardiography: does it improve the management of cardiovascular disease in the community? AB - In this study the use of exercise electrocardiography, by 47 general practitioners in South East Kent has been evaluated. Of 110 consecutive requests the majority (88%) were for diagnostic purposes, while only 7% were for prognostic assessment. Many of those referred were young or had non-cardiac chest pain and in 59% of cases the test result was unlikely to alter the clinical assessment of the probability of ischaemic heart disease (IHD). The test result influenced patient management in 85% of cases. Only 15% of patients were subsequently referred to the district general hospital although all had been considered for referral prior to the test. Although referral for invasive investigation of six patients was expedited by the provision of stress testing, in five patients general practitioners failed to consider any further investigation despite the patient having a strongly positive test. General practitioners use exercise electrocardiography primarily to exclude IHD in patients at low risk and provide reassurance. They rarely use the test as a means to guide management of those with known or probable IHD. PMID- 2325055 TI - Acute changes in atherogenic and thrombogenic factors with cessation of smoking. AB - Tobacco smoking is associated with alterations in several factors considered to be important in the atherosclerotic process. Thirty chronic smokers were studied 2 weeks before and 2 weeks after complete tobacco withdrawal. Significant reductions in fibrinogen, haematocrit, plasma viscosity and whole blood viscosity as well as a significant increase in HDL-cholesterol were observed. As these factors are important in both atherogenesis and thrombogenesis, these observations may give insight into tobacco-induced atherosclerotic disease and may be responsible for the more rapid reduction in the incidence of cardiovascular disease that is believed to occur after stopped smoking. PMID- 2325056 TI - Dipstick haematuria: its association with smoking and nonsteroidal anti inflammatory drugs. AB - Of 1015 men over the age of 60, 125 (12.3%) were found to have dipstick haematuria on a single test. Analysis of smoking history revealed a 1.6 fold increased incidence of dipstick haematuria in current smokers as compared with ex smokers and non-smokers. The relationship with bladder cancer and smoking is discussed. Several commonly used drugs, including nonsteroidal anti-inflammatory preparations, have been implicated as a cause of urinary tract bleeding. In this study of 1015 men over the age of 60, no association was found between the presence of dipstick haematuria and the intake of aspirin, other nonsteroidal anti-inflammatory drugs or warfarin. PMID- 2325057 TI - Rectal cancer after pelvic irradiation. AB - During a 6 month period in 1988 five women were treated at Colchester General Hospital for carcinoma of the rectum, each more than 10 years after undergoing pelvic irradiation. Although irradiation has not been proven to induce human colorectal cancer, considerable circumstantial and experimental evidence supports this belief. Features suggestive of radiation-induced colorectal cancer are the presence of radiation-damaged bowel adjacent to the carcinoma and a mucus secreting ('colloid') histological pattern. The increasing number of women being exposed to rectal irradiation in the course of treatment of gynaecological malignancy may result in an increase in the incidence of radiation-induced rectal cancer. Awareness of this potential long-term complication is important when planning follow-up of patients subjected to pelvic radiotherapy. PMID- 2325058 TI - Drug-induced epistaxis? AB - To assess the aetiological contribution made to spontaneous epistaxis in adults over the age of 50 years by various groups of drugs, a controlled study was designed. Fifty-three consecutive epistaxis patients were compared with 50 controls. Significant differences were found between the groups in their consumption of warfarin, dipyridamole and non-steroidal anti-inflammatory drugs. Hypertension was equally common in the two groups, but tended to be less well controlled in the epistaxis patients compared to the controls. It is thought that the link between the use of nonsteroidal anti-inflammatory drugs and the occurrence of epistaxis may be due to alteration of platelet function. PMID- 2325059 TI - Detection of ocular malignancies. AB - The case notes of new patients attending the oncology clinic at Moorfields Eye Hospital during the first 5 months of 1988 were analysed retrospectively with regard to the origin of the primary referral, the presence of symptoms, the diagnosis and management. Sixty-eight of 94 new patients were diagnosed as having malignant ocular lesions. Of these 68, 47% were first seen and referred by an optician. Half of these patients were asymptomatic at the time of detection. PMID- 2325060 TI - Avoiding inappropriate surgery: discussion paper. PMID- 2325061 TI - The delivery of health care alternatives: discussion paper. PMID- 2325063 TI - The shrinking seminoma. PMID- 2325062 TI - Dangerous synergism between sedatives and a hyponatraemic state. PMID- 2325064 TI - Acquired hypertrichosis terminalis in bronchial carcinoma. PMID- 2325065 TI - Subcutaneous Salmonella abscess--an unusual manifestation of salmonellosis. PMID- 2325067 TI - Tinted spectacles. PMID- 2325066 TI - Endobronchial metastasis from parotid gland tumour. PMID- 2325068 TI - Thrombolysis for acute myocardial infarction. PMID- 2325069 TI - Bilothorax--an unusual problem. PMID- 2325071 TI - Myalgic encephalomyelitis. PMID- 2325070 TI - Irritable bowel syndrome. PMID- 2325072 TI - Educating the hypertensive patient--teaching the teacher. Proceedings of an international workshop organized by the World Hypertension League. Tel Aviv, Israel, December 1988. PMID- 2325073 TI - Summary statements on selected aspects of educating hypertensive patients. Workshop participants. PMID- 2325074 TI - Patient education in selected countries. PMID- 2325075 TI - The results: impact and outcome of patient education. PMID- 2325076 TI - Addressing the entire risk profile. PMID- 2325077 TI - Practice organization and management for patient education. PMID- 2325078 TI - Working with groups of patients. PMID- 2325079 TI - The objectives: what do we want to achieve by patient education? PMID- 2325080 TI - In-hospital information: the Geneva experience. PMID- 2325081 TI - Physician-patient workshops. PMID- 2325082 TI - Addressing larger audiences: community programmes. PMID- 2325083 TI - Patient education and public education: separate, overlapping or complementary? PMID- 2325084 TI - Teaching doctors to teach patients. PMID- 2325085 TI - Objectives for teaching patient education. PMID- 2325086 TI - Initiating faculty development: the WHL workshop as a learning experience. PMID- 2325087 TI - A Chinese familial growth hormone deficiency with a deletion of 7.1 kb of DNA. AB - Using restriction endonuclease analysis and a human growth hormone cDNA probe, we have found a Chinese family with a human growth hormone gene deletion. Two affected sibs are homozygous for a deletion of approximately 7.1 kb of DNA, which contains the normal human growth hormone gene. The patients' parents and grandmothers are heterozygous for the deleted gene. Their grandfathers are normal and homozygous for the hGH-N gene. All of them have normal stature. PMID- 2325088 TI - Small marker chromosomes in man: origin from pericentric heterochromatin of chromosomes 1, 9, and 16. AB - Three patients with different marker chromosomes were screened by in situ hybridisation using biotinylated probes to chromosome specific pericentric repeats to determine the chromosomal origin of the marker. Each marker had a different origin, with one from each of chromosomes 1, 9, and 16. This is the first time that autosomal marker chromosomes consisting of a small ring have been shown to be derived from the pericentric heterochromatin of metacentric and submetacentric chromosomes. Evidence suggests that such markers are not associated with any significant risk of phenotypic abnormalities, but additional cases need to be studied. PMID- 2325090 TI - EEC syndrome without ectrodactyly: report of two new families. AB - In this report we describe two families with variable manifestations of the EEC syndrome. The findings in these families confirm that no symptom is obligatory for the diagnosis of EEC syndrome. In the absence of cleft lip/palate, EEC patients have a characteristic facial morphology with maxillary hypoplasia, short philtrum, and broad nasal tip. PMID- 2325089 TI - Cranial hemihypertrophy and neurodevelopmental prognosis. AB - Three cases of congenital cranial hemihypertrophy are described. CT or ultrasound scans showed unilateral cerebral enlargement with dilatation of the ipsilateral ventricle. Seizures occurred in two patients and the neurodevelopmental outlook appears poor. These patients represent a poor prognosis subgroup of the congenital hemihypertrophies. PMID- 2325091 TI - Pontobulbar palsy and neurosensory deafness (Brown-Vialetto-Van Laere syndrome) with possible autosomal dominant inheritance. AB - A female with the Brown-Vialetto-Van Laere syndrome is described. The patient's father, a paternal uncle, and possibly a paternal first cousin had neurosensory deafness and a paternal aunt had clinical symptoms indicative of the syndrome. This family raises the possibility that the disorder is genetically heterogeneous with autosomal recessive and autosomal dominant forms. Alternatively, it could be caused by a mutant gene on the X chromosome. PMID- 2325092 TI - Focal dermal hypoplasia (Goltz syndrome). PMID- 2325093 TI - Multiple abnormalities in a child with partial duplications of 10p and 13q from a 3:1 segregation of a maternal t(10;13) translocation. AB - Partial duplications of 10p and 13q in association with partial deletions of other chromosome segments have been variously reported. We describe here a female child with multiple congenital abnormalities and combined partial duplications of 10p and 13q resulting from a 3:1 segregation of a maternal t(10;13)(p13;q22). In comparing the phenotypic features of the two chromosome imbalances, the expression of features typical of partial duplication 10p appeared more pronounced. PMID- 2325094 TI - Microphthalmia with single central incisor and hypopituitarism. AB - A patient is described with a new association of microphthalmia, single central incisor, and hypopituitarism believed to represent a holoprosencephaly malformation. In view of the genetic ramifications of this malformation and its variable manifestations, we would like to alert the clinician to consider holoprosencephaly whenever midline malformations are detected. PMID- 2325095 TI - A case of atelosteogenesis. AB - Atelosteogenesis is a rare chondrodysplasia characterised by rhizomelic short limbed dwarfism, thoracic hypoplasia, multiple joint dislocations, talipes equinovarus, and early death. The diagnosis is confirmed radiologically: short, distally tapering humeri, absent or hypoplastic fibulae, deficient vertebral ossification with coronal clefting, and anarchic ossification of phalanges are characteristic findings. We report a male child with this condition born to first cousin Bengali parents. PMID- 2325097 TI - Orofaciodigital syndrome type IV (Mohr-Majewski syndrome) with severe expression expanding the known spectrum of anomalies. AB - We present a male infant with hypertelorism, median pseudo-cleft of the upper lip and cleft palate, lobulated tongue, hypoplastic larynx and epiglottis, mesomelic shortening of limbs with particularly short and broad tibiae, polydactyly of the upper limbs, severely hypoplastic external genitalia with anorchidism, anal atresia, severe congenital heart defect, and renal agenesis. These features show considerable overlap with severe Majewski type short rib-polydactyly syndrome and so expand the known spectrum of anomalies in orofaciodigital syndrome type IV. PMID- 2325096 TI - Identical twins discordant for Kallmann's syndrome. AB - A 20 year old male patient presented with lack of sexual development. On examination he was eunuchoidal and hypogonadal, and olfactory function testing showed he was anosmic. Biochemical investigations proved he was hypogonadotrophic. Kallmann's syndrome was therefore diagnosed. His appearance was very different from his alleged identical twin who had undergone a normal puberty and had normal plasma testosterone and gonadotrophin levels. However, the twin was hyposmic. Genetic fingerprinting confirmed the twins were identical. Why Kallman's syndrome was incompletely expressed in one of them is unexplained. The parents and a normally menstruating sister had normal olfactory function. PMID- 2325098 TI - Abstracts of the meeting of the Clinical Genetics Society. 5 and 6 October 1989, Middlesex. PMID- 2325099 TI - Choanal atresia as a feature of ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome: a further case. PMID- 2325100 TI - Osteoglophonic dysplasia. PMID- 2325101 TI - Paraplegia and arthrogryposis multiplex of the lower extremities after intrauterine exposure to ergotamine. PMID- 2325102 TI - The clinical features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by arginine in the pro alpha 1(I) chain of type I procollagen. AB - The features of three babies with lethal perinatal osteogenesis imperfecta resulting from the substitution of glycine by arginine in the pro alpha 1(I) chain of type I procollagen were studied. The babies were heterozygous for this substitution at residue 391 in case 1 (0I24), 667 in case 2 (0I51), and 976 in case 3 (0I30). They were all small, term babies who died soon after birth. The ribs were broad and continuously beaded in 0I24, discontinuously beaded in 0I51, and slender with few fractures in 0I30. The overall radiographical classifications were type IIA in 0I24, IIA/IIB in 0I51, and IIB in 0I30. Histological examination confirmed that the long bones were misshapen and porotic. The calcified cartilage trabeculae were covered with an abnormally thin layer of osteoid and the bone trabeculae were thin and basophilic. There was no evidence of lamellar bone or Haversian systems. The osteoblasts remained relatively large and closely spaced. These babies shared many phenotypic features, but differences in the radiographical appearance of the ribs and long bones suggested that there was a gradient of bone modelling capacity from the slender and overmodelled bones in 0I30 to the absence of modelling in 0I24. PMID- 2325103 TI - Becker muscular dystrophy: correlation of deletion type with clinical severity. AB - Molecular deletion screening with cDNA probes from the dystrophin gene was undertaken in patients with Becker muscular dystrophy from 58 separate families. Deletions were found in 41 (71%) of these families. Thirty-four (83%) of the deletions started in the same intron near the centre of the gene, and although there was no precise correlation between clinical severity and deletion pattern, the commonest deletion pattern, which was present in 49% of all deletion families, is associated with a mild phenotype. PMID- 2325104 TI - Reliability of prenatal diagnosis of genetic diseases by analysis of amplified trophoblast DNA. AB - Dot blot analysis on enzymatically amplified trophoblast DNA with allele specific oligonucleotide probes is currently used for the prenatal diagnosis of single gene disorders characterised at the molecular level, such as the beta thalassaemias, phenylketonuria, sickle cell anaemia, and alpha 1-anti-trypsin deficiency. A potential problem with the use of this procedure is the co amplification of maternal sequences, which may obscure the diagnosis in the fetus. To address this question, we carried out prenatal diagnosis of beta thalassaemia in 300 couples at risk by dot blot analysis on enzymatically amplified DNA with 32P or horseradish peroxidase labelled allele specific oligonucleotide probes. We verified the diagnosis obtained by this procedure with oligonucleotide hybridisation on electrophoretically separated non-amplified trophoblast DNA fragments. We detected no co-amplified maternal sequences, even with a faint signal, in the dot blot of trophoblast DNA from those fetuses diagnosed as normal or homozygotes, nor in those diagnosed as heterozygotes, who were born to parents carrying different mutations and had inherited the paternal mutation. These results indicate that, when careful dissection of trophoblast tissue from maternal decidua is carried out, amplification of chorionic villi DNA is not associated with amplification of maternal DNA sequences. We may thus conclude that dot blot analysis of trophoblast DNA is a very reliable procedure for prenatal diagnosis. PMID- 2325105 TI - Ellis-van creveld syndrome, Jeune syndrome, and renal-hepatic-pancreatic dysplasia: separate entities or disease spectrum? AB - We describe two children with multiple abnormalities, neither of whom fits neatly into a classical diagnostic category, but who show overlapping features of Ellis van Creveld syndrome, Jeune syndrome, and renal-hepatic-pancreatic dysplasia. It seems possible that these three entities form part of a disease spectrum rather than being distinct conditions. PMID- 2325106 TI - Wiedemann-Rautenstrauch syndrome. PMID- 2325107 TI - Rothmund-Thomson syndrome associated with trisomy 8 mosaicism. AB - This report describes a boy with Rothmund-Thomson syndrome associated with trisomy 8 mosaicism. The patient presented with typical features of Rothmund Thomson syndrome but some of the features often seen in trisomy 8 mosaics were also observed in him. The possibility that the two disorders might share a common pathogenesis is postulated. PMID- 2325108 TI - A constitutional 5q23 deletion. AB - A 14 month old girl was found to have a deletion of the whole of band 5q23. By comparing 19 other cases monosomic for a part of the 5q13-q31 segment, the constitutional 5q interstitial deletions fall into two groups: adult patients with Gardner-like symptoms and mental retardation associated with deletion 5q21 q22, and patients (mostly children) with unspecific signs and symptoms and different deletions. PMID- 2325109 TI - Fetal brain disruption sequence: a milder variant. AB - We report on a female infant with severe microcephaly, scalp rugae, overlapping sutures, and telancephalic damage with relatively satisfactory early motor development. This case represents a milder form of the 'fetal brain disruption sequence', which is thought to be the result of an exogenous insult to the developing brain during the second half of gestation. PMID- 2325110 TI - The SNATIATION reflex. PMID- 2325111 TI - Angelman's syndrome. PMID- 2325113 TI - Proceedings of the Pathological Society of Great Britain and Ireland. London, January 3,4 and 5, 1990. Synopses of papers with microbiological interest. PMID- 2325112 TI - Recurrence of acheiria in a second cousin: extremely large pedigrees may include 'second cases' by chance. PMID- 2325114 TI - Enzyme immunoassay (ELISA) for detection of Clostridium difficile toxin B in specimens of faeces. AB - Antisera against Clostridium difficile toxin B were prepared in sheep and rabbit and were used in indirect and sandwich enzyme-linked immunosorbent assays (ELISA) for the detection of toxin B. Polyvinyl chloride and polystyrene microtitration plates were tested as solid phases for the assay. Both assays had a lower limit of detection for toxin B of 1 ng/ml. They were used to detect the presence of toxin B in 210 human faecal specimens and also in the culture supernatant fluids of C. difficile strains isolated from the faecal samples. There was a close correlation between the results of sandwich ELISA and those of cytotoxicity tests and isolation of C. difficile. Our sandwich ELISA method seems to be useful as a presumptive test for detection of C. difficile toxin B. PMID- 2325115 TI - Surface-associated properties of Streptococcus milleri group strains and their potential relation to pathogenesis. AB - Thirty strains from the Streptococcus milleri (anginosus) group (SMG) obtained from various sources were tested for a range of characters that could be associated with pathogenicity and the results were compared with those for type strains of S. sanguis, S. mutans and S. pyogenes. The SMG strains were heterogeneous in all tests. Most (18) belonged to one of the Lancefield groups with group F predominating. Adherence of strains isolated from abscesses to buccal epithelial cells was greater than that of other strains (p = 0.033). Compared with strains of S. sanguis, SMG strains were generally not aggregated by human saliva. They differed from the type strain of S. pyogenes in their relative ability to bind fibrinogen and fibronectin; they were less effective in binding fibrinogen (0.33-4.28% cf. 22% for S. pyogenes) and generally more effective in binding fibronectin (0.49-12.37% cf. 0.95%). Strains isolated from infections were statistically better at binding fibronectin than other strains (p less than 0.001). The ability of strains to adhere to saliva-coated hydroxyapatite (SHA) varied 10-fold, from 0.16-16.35%. The amount of fibronectin bound by SMG strains correlated with their ability to adhere to SHA (p less than 0.001). The hydrophobicity of the strains, as measured in the hexadecane partition assay, ranged from 0.0% to 99.0%. Some strains carried both positive and negative cell surface charges and some strains with a highly hydrophobic cell surface also possessed a relatively high cell-surface charge. A minority of strains possessed a net positive cell-surface charge. Neither hydrophobicity nor cell-surface charge was related to the capacity of strains to adhere to SHA. Strains of SMG co aggregated weakly with strains of Veillonella parvula, V. dispar, Actinomyces viscosus and A. naeslundii. PMID- 2325116 TI - The incidence of anaerobes in the sputum of patients with cystic fibrosis. AB - The number of anaerobes in selected sputum samples from patients with cystic fibrosis (CF) was investigated. When cultured by a semi-quantitative method, 26 (23.85%) of 109 sputum specimens from 21 CF patients contained greater than 10(5) cfu of anaerobic organisms/ml. Nine (42.7%) of the 21 patients produced sputum containing such concentrations of anaerobes on at least one occasion. Anaerobes were isolated from repeated sputum specimens from five patients. The anaerobes most often isolated were Bacteroides disiens, pigmented Bacteroides spp. and anaerobic gram-positive cocci. Anaerobes were isolated more often from sputum liquefied by sonication than from unliquefied sputum, suggesting that they were unlikely to be oropharyngeal contaminants. PMID- 2325117 TI - Surface dielectric constant, surface hydrophobicity and membrane fusion. AB - Membrane fusion induced by ions and its associated membrane property, surface dielectric constant, were studied with the use of acidic and neutral phospholipid vesicles. The fusion of vesicles was monitored by utilizing two fluorescence fusion assays: fluorescence content mixing method and fluorescence labelled membrane component dilution method. For the surface dielectric constant measurements, a fluorescence method was used which detected the environmental effect on the membrane surface upon the addition of various fusogenic cations. Also, the effects of poly-(ethylene glycol) on both fusion and surface dielectric properties were examined. It was found that the extent of fusion correlated well with the degree of lowering in the dielectric constant of the surface membrane, which corresponds to the increase in hydrophobicity of the membrane surface. This agrees with the previously obtained experimental results that the increase in interfacial tension of the membrane, which also corresponds to the increase in surface hydrophobicity, correlates with the extent of membrane fusion. PMID- 2325118 TI - Gene map of mental retardation. AB - A gene map based on a compilation of genetic disorders involving mental retardation is presented. The presentation is divided into three parts; the first part describes 69 genes assigned to an autosome, the second part consists of the 73 genes assigned to the X-chromosome, and the third part consists of genetic disorders without any known chromosome location. PMID- 2325119 TI - A genetic diagnostic survey in an institutionalized population of 262 moderately mentally retarded patients: the Borgerstein experience. AB - In this paper, the authors report the results of a genetic-diagnostic survey of 262 instutionalized moderately mentally retarded patients and compare these data with their previous studies of the severely mentally retarded. Special attention is given towards the nosology of X-linked mental retardation and familial mental retardation in general. PMID- 2325120 TI - A population-based study of mild mental handicap in children: preliminary analysis of obstetric associations. AB - One hundred and twenty-nine children in the 8- to 12-year-old age group in Cardiff were ascertained to have mild mental deficiency. Detailed obstetric data were obtained which indicated that nearly 69% of the children were associated with adverse obstetric factors. Fifty-five per cent had the combined pathogenetic risk factors of pre-, peri- and neonatal adversities. Forty-two per cent of the cases had non-optimal perinatal factors and 45% were considered to have prenatal causation. There were four children with chromosomal anomalies. The various adverse obstetric influences are discussed separately. PMID- 2325121 TI - Folate treatment of a boy with fragile-X syndrome. AB - A severely behaviourally disturbed three year old boy with the fragile-X syndrome was treated with intermittent folate therapy over a period of 2 years. No behavioural improvement was noted in this time but variations between cultural regimes for the successful detection of the fragile-X marker were observed. PMID- 2325122 TI - Association of acrocyanosis with Asperger's syndrome. AB - The authors present three men with both acrocyanosis and Asperger's syndrome. Though the general incidence of acrocyanosis is unknown, they suggest that it is probably more common in autistic disorders and may be caused by hyperserotonaemia. PMID- 2325124 TI - Physician: answer the school bell in your community. PMID- 2325123 TI - Trisomy 13 (Patau's syndrome): a rare case of survival into adulthood. AB - Survival of cases of trisomy 13 (Patau's syndrome) into adulthood is a rare phenomenon. The purpose of this paper is to report one such survivor who has had the typical clinical features of trisomy 13 confirmed by chromosome analysis of both blood and skin, and to speculate on some of the factors that may have contributed to his unusually long survival. PMID- 2325125 TI - COBRA's anti-dumping provisions: fertile ground for hospital and physician liability. PMID- 2325126 TI - Is there a safe alternative to smoking? PMID- 2325127 TI - Crystallization of hevamine, an enzyme with lysozyme/chitinase activity from Hevea brasiliensis latex. AB - Hevamine, an enzyme with both lysozyme and chitinase activity, was isolated and purified from Hevea brasiliensis (rubber tree) latex. The enzyme (molecular weight 29,000) is homologous to certain "pathogenesis-related" proteins from plants, but not to hen egg-white or phage T4 lysozyme. To investigate the atomic details of the substrate specificity and the cause for hevamine's low pH optimum (pH 4.0), we have crystallized two hevamine isozymes as a first step towards a high-resolution X-ray structure determination. Suitable crystals were obtained at room temperature from hanging drop experiments by vapor diffusion against 1.7 M to 3.4 M-NaCl (pH 5.0 to 9.0) for the major isozyme, and by vapor diffusion against 2.5 M to 4.3 M-NaCl (pH 5.0 to 8.0) for the minor one. Both isozymes give the same crystal morphology and space group. Their space group is P2(1)2(1)2(1) with cell dimensions a = 82.3 A, b = 58.1 A and c = 52.5 A (1 A = 0.1 nm). The crystals diffract to at least 2.0 A resolution. PMID- 2325128 TI - Crystallographic characterization of a Cu,Zn superoxide dismutase from Photobacterium leiognathi. AB - Crystals of a copper-zinc superoxide dismutase from Photobacterium leiognathi, a luminescent marine bacterium that is the species-specific symbiont of the ponyfish, have been obtained from 2-methyl-2,4-pentanediol solutions. The space group was determined using screenless small-angle precession photographs, and was confirmed by analyzing area detector diffraction data with the XENGEN programs for indexing and refinement. The crystals are monoclinic, space group C2 (a = 126.4 A, b = 87.0 A, c = 44.4 A, beta = 92.8 A), and have two 32,000 Mr dimers per asymmetric unit. The crystals diffract to at least 2.7 A resolution, are resistant to radiation damage, and are suitable for determination of the structure by X-ray diffraction. PMID- 2325129 TI - Co-operative activation of skeletal muscle thin filaments by rigor crossbridges. The effect of troponin C extraction. AB - When Ca2+ binds to troponin C (TnC), all 26 troponin-tropomyosin (Tn-Tm) complexes of a regulatory strand change in concert from the inactive to the active configuration. To see if the complexes respond similarly when they are activated by rigor crossbridges in the absence of Ca2+, we determined the slope (ns) of the bell-shaped pS/tension (pS = -log [MgATP], where S = MgATP2-) relationship between pS 5, where the tension is maximal, and pS 2.3, where fibers are fully relaxed. In control skinned rabbit psoas fibers the ns value is greater than 4; it progressively decreases with TnC extraction. This decrease in ns with TnC extraction is analogous to the decrease in the slope (Hill coefficient) of the pCa/tension (pCa = -log [Ca2+]) relationship with extraction. Complete TnC extraction reduces the maximum substrate-induced tension by only 25%; in contrast, it reduces the maximum Ca2+ induced tension to zero. The effects of TnC extraction on the slope of the pS/tension curve are explained by the assumptions that (1) extracted Tn-Tm complexes no longer change in concert with their neighbors but change independently of them, and (2) co-operative signals cannot cross extracted Tn-Tm complexes. The ns value, therefore, like the nH, is a direct function of the number of contiguous, intact, Tn-Tm complexes in a stretch of a regulatory strand. To describe qualitatively the bi-phasic pS/tension relationship, the mono-phasic pCa/tension relationship, and the effects of TnC extraction on them, we introduce a version of the concerted-transition formalism which includes two activating ligands, Ca2+ and rigor crossbridges. PMID- 2325130 TI - Reversible and irreversible changes in nucleosome structure along the c-fos and c myc oncogenes following inhibition of transcription. AB - A new affinity chromatographic procedure for the separation of transcriptionally active nucleosomes has been used to study the changes that take place in chromatin structure along the c-fos and c-myc genes when RNA synthesis is inhibited. Mercury-affinity chromatography separates the sulfhydryl-reactive nucleosomes of transcriptionally active genes from the compactly beaded, non reactive nucleosomes of transcriptionally inert DNA sequences. The new procedure also discriminates between nucleosomes that have "unfolded" to reveal the previously shielded SH groups of histone H3 and nucleosomes that bind to the mercury column because of their association with thiol-containing non-histone proteins located in the transcription unit. Both classes of Hg-bound nucleosomes contain the c-fos and c-myc sequences, but only when they are being transcribed. We compared the effects of alpha-amanitin and actinomycin D on the transcription of c-fos and c-myc with the effects of each inhibitor on the distribution of the corresponding oncogenic DNA sequences in the chromatographically separated nucleosome fractions. It was found that the inhibition of RNA polymerase II by alpha-amanitin (added at the peaks of c-fos or c-myc expression in serum stimulated BALB/c 3T3 cells) resulted in a rapid loss of affinity of the oncogene containing nucleosomes for the mercury column. There was no corresponding effect on the mercury-binding properties of nucleosomes containing 28 S ribosomal gene sequences, which continue to be transcribed by amanitin-resistant RNA polymerase I. Therefore, the binding of the c-fos and c-myc nucleosomes to the mercury column seems to depend upon reversible structural changes associated with their transcription. Surprisingly, there was no corresponding loss of affinity of the c fos and c-myc nucleosomes for the mercury column when actinomycin D was employed to inhibit RNA synthesis, despite the fact that transcription of both genes had been arrested abruptly. Measurements of [3H]actinomycin D binding show its preferential intercalation into the transcriptionally active nucleosomes. We suggest that the intercalation of actinomycin D into the DNA of active nucleosomes can lock the transcription complex into an "unfolded" but potentially active configuration. This was confirmed by run-off transcription assays showing a restoration of c-fos and c-myc RNA synthesis when actinomycin D was displaced by proflavine. PMID- 2325131 TI - Structure of nucleosomes and organization of internucleosomal DNA in chromatin. AB - We have compared the mononucleosomal pattern produced by micrococcal nuclease digestion of condensed and unfolded chromatin and chromatin in nuclei from various sources with the repeat length varying from 165 to 240 base-pairs (bp). Upon digestion of isolated H1-containing chromatin of every tested type in a low ionic strength solution (unfolded chromatin), a standard series of mononucleosomes (MN) was formed: the core particle, MN145, and H1-containing, MN165, MN175, MN185, MN195, MN205 and MN215 (the indexes give an approximate length of the nucleosomal DNA that differs in these particles by an integral number of 10 bp). In addition to the pattern of unfolded chromatin, digestion of whole nuclei or condensed chromatin (high ionic strength of Ca2+) gave rise to nuclei-specific, H1-lacking MN155. Digestion of H1-lacking chromatin produced only MN145, MN155 and MN165 particles, indicating that the histone octamer can organize up to 165 bp of nucleosomal DNA. Although digestion of isolated sea urchin sperm chromatin (repeat length of about 240 bp) at a low ionic strength gave a typical "unfolded chromatin pattern", digests of spermal nuclei contained primarily MN145, MN155, MN235 and MN245 particles. A linear arrangement of histones along DNA (primary organization) of the core particle was found to be preserved in the mononucleosomes, with the spacer DNA length from 10 to 90 bp on one (in MN155) or both sides of core DNA being a multiple of about 10 bp. In MN235, the core particle occupies preferentially a central position with the length of the spacer DNA on both sides of the core DNA being usually about 30 + 60 or 40 + 50 bp. Histone H1 is localized at the ends of these particles, i.e. close to the centre of the spacer DNA. The finding that globular part of histones H3 and sea urchin sperm H2B can covalently bind to spacer DNA suggests their involvement in the organization of chromatin superstructure. Our data indicate that decondensation of chromatin is accompanied by rearrangement of histone H1 on the spacer DNA sites adjacent to the core particle and thus support a solenoid model for the chromatin superstructure in nuclei in which the core DNA together with the spacer DNA form a continuous superhelix. PMID- 2325132 TI - Adenosine A1 receptor mediated protection of the globally ischemic isolated rat heart. AB - The purpose of this study was to determine if the cardioprotective effect of adenosine on the ischemic myocardium is mediated by interaction with specific adenosine receptor subtypes. Isolated rat hearts perfused at constant flow were subjected to global normothermic (37 degrees C) ischemia and the time to onset of ischemic contracture (TOIC) was used as a marker of myocardial ischemic injury. Hearts treated with adenosine and R-phenylisopropyladenosine (PIA), an adenosine A1 receptor agonist, exhibited a significantly greater TOIC than control hearts (18.60 +/- 0.40 and 16.64 +/- 1.15 min, respectively vs 9.12 +/- 0.66 min), whereas phenylaminoadenosine, an adenosine A2 receptor agonist, had no effect on TOIC (11.73 +/- 0.87 min). BW A1433U, an adenosine receptor antagonist, blocked the effects of adenosine and PIA on ischemic contracture time, and BW A1433U did not alter the ability of nifedipine or propranolol to delay the onset of ischemic contracture, thus indicating the specificity of this compound for the adenosine receptor. PIA-treated hearts exhibited significantly greater ATP levels throughout the ischemic period compared to control hearts, whereas hearts treated with BW A1433U showed a rapid decline in ATP content. These results suggest that the beneficial effects of adenosine on the ischemic myocardium are mediated by interaction with adenosine A1 receptors, and that endogenously formed adenosine plays a role in attenuating myocardial ischemic damage. PMID- 2325133 TI - Cerium chloride as a histochemical marker of hydrogen peroxide in reperfused ischemic hearts. AB - Hydrogen peroxide (H2O2) has been implicated in cardiac damage due to ischemia and reperfusion. We adapted an electron microscopic, histochemical method for demonstrating H2O2 produced by isolated cells to isolated, buffer-perfused rabbit hearts. The method involves formation of an electron-dense precipitate when H2O2 reacts with cerium chloride (CeCl3). We perfused hearts retrograde via the aorta with well-oxygenated bicarbonate-buffered solution, followed by one in which bicarbonate was replaced with imidazole (IPSS) to prevent precipitation of bicarbonate and CeCl3. Some hearts were made globally ischemic (30 min, 37 degrees C), reperfused 5 min with well-oxygenated IPSS containing 1 mM CeCl3, then processed for electron microscopy. Others were perfused with IPSS containing catalase (300 U/ml) or albumin before ischemia and upon reperfusion, followed by CeCl3 administration. Nonischemic control hearts perfused with IPSS (+/- catalase) were also studied. Electron micrographs were assessed visually and by computer for precipitate localization and amount. There was abundant precipitate on the luminal face of the coronary vascular endothelium in ischemic-reperfused, cerium-treated hearts, including those treated with albumin. There was significantly less in reperfused catalase-treated or nonischemic control hearts. X-ray microbeam analysis of the endothelial precipitate indicated the presence of Ce. This appears to be the first visual demonstration of a CeCl3-H2O2-dependent reaction product in intact isolated ischemic hearts. The data indicate that at the time of reperfusion some H2O2 is accessible to the vascular space, and that its amount can be reduced by perfused catalase. Further modifications this technique may be useful for assessing the sites and pathways by which H2O2 is generated by hearts or other buffer-perfused organs subjected to stresses such as ischemia or hypoxia. PMID- 2325134 TI - Effects of repeated low calcium perfusion on the rat heart: a gradual induction of calcium related damage. AB - The calcium paradox occurs immediately upon perfusion with calcium-containing medium after a period of calcium-free perfusion. The sequence of events occur so rapidly that it is difficult to distinguish causal factors from resultant. The present study describes a model in which calcium induced damage is produced more gradually. Isolated perfused rat hearts were subjected to brief periods of hypocalcium perfusion (less than 50 microM) alternated with normal calcium perfusion (1.25 mM) over 60 min. Changes in high energy phosphate content were monitored using 31P-NMR. With repeated sequential 2-min periods of alternate hypo and normocalcium perfusion, there was a gradual reduction in ATP and phosphocreatine with a concomitant loss of function and decline in coronary flow. There was no change in inorganic phosphate content and a small degree of acidosis. Increasing the hypocalcium concentration from 5 to 40 microM resulted in a more gradual depletion in energy stores. Trifluoroperazine (a calmodulin inhibitor) had no effect on the energetic changes. Electron microscopic studies reveal that this model of damage induced by repeated low and normal calcium perfusion has some features in common with the calcium paradox. The extent of damage induced is greater when lower calcium concentrations (5 microM) are used. PMID- 2325135 TI - Effects of nicotinic acid and mepacrine on fatty acid accumulation and myocardial damage during ischemia and reperfusion. AB - To assess the nature of ischemia- and reperfusion-induced lipid changes and their consequences for myocardial function and integrity, Krebs-Henseleit perfused, isolated, working rat hearts were treated with nicotinic acid or mepacrine, putative inhibitors of triacylglycerol and phospholipid hydrolysis, respectively. In non-treated hearts 60 min ischemia resulted in a marked rise in myocardial fatty acid (FA) content. The FA content sharply increased further during 30 min reperfusion. Seven out of 16 (44%) hearts fibrillated continuously during reperfusion. Post-ischemic recovery of cardiac output (CO) of the non fibrillating hearts amounted to 68 +/- 15% of the preischemic value. Nicotinic acid (10 microM) significantly reduced FA accumulation during ischemia (P less than 0.05), but not during reperfusion (0.05 less than P less than 0.10). Post ischemic recovery of CO was improved (87 +/- 12%). This was neither associated with preservation of myocardial adenine nucleotide content, nor significant reduction of enzyme release. Mepacrine (1 microM) completely abolished reperfusion arrhythmias and improved recovery of CO (88 +/- 7% of pre-ischemic value). The reduction of FA content in ischemic and reperfused hearts did not reach the level of significance. Enzyme release was not attenuated. At 10 microM, mepacrine completely prevented accumulation of FAs during ischemia and reperfusion, abolished reperfusion-arrhythmias, and reduced enzyme release. No concomitant preservation of adenine nucleotides was observed. In conclusion, nicotinic acid and mepacrine are able to reduce ischemia- and reperfusion-induced changes in myocardial lipid metabolism. In addition, both drugs improve post ischemic functional recovery. It remains to be established whether these effects are causally related. PMID- 2325136 TI - An in vitro model of myocardial ischemia utilizing isolated adult rat myocytes. AB - Isolated adult rat myocytes were used to develop an in vitro model of myocardial ischemia. Freshly isolated myocytes were spun into a cell pellet to limit extracellular volume. Excess supernatant was removed and the pellet was covered with mineral oil and incubated in a temperature controlled water bath. After various periods of incubation, cells were analyzed for adenine nucleotide levels, lactate accumulation, rate of cell death, and cell morphology. Adenine nucleotide profiles after 60 min incubation at 37 degrees C showed marked depletion of adenosine triphosphate (ATP) and large increases in adenosine monophosphate (AMP), adenosine, inosine, and lactate and no significant difference in levels of inosine monophosphate. These results are consistent with ischemic conditions. Reduction of the incubation temperature to 34 and 30 degrees C slowed the rate of cell squaring and the onset of cell death. Resuspension of ischemic cells after 30, 45, 60 and 90 min incubation in hypotonic buffer (170 mosmol) to induce acute cell swelling caused an increase in the number of non-viable cells at each time point. Control cells and ischemic cells incubated less than 30 min did not show increases in non-viable cells when subjected to hypotonic swelling. Morphological analysis revealed that isolated myocytes respond to ischemia in a heterogeneous fashion and exhibit changes at both light and electron microscopic levels similar to those seen in other ischemic models. These results indicate that pelleted isolated adult rat myocytes may be a useful in vitro model to study myocardial ischemic cells injury. PMID- 2325137 TI - Free energy of ATP-hydrolysis fails to affect ATP-dependent potassium channels in isolated mouse ventricular cells. AB - The single channel recording technique has been used to study the adenosine-5' triphosphate (ATP)-dependent K+ channel in isolated mouse ventricular cells. The aim of this work was to determine if the activity of the K+ channel depends on the free energy of ATP-hydrolytic reaction (phosphorylation potential) in addition to the well-studied direct block by ATP. When the phosphorylation potential was changed from 60 to 50, to 40 and back to 60 kJ/mol at a constant ATP-concentration of 10(-4) mol/l, the ATP-channel activity showed a run down that is best described by a linear function. Changing the ATP-concentration of the bath solution from 0.01 to 1 and back to 0.01 mmol/l by a factor of 10 at a constant phosphorylation potential of 50 kJ/mol, resulted in a run down of the mean average current by a reduction of the open state probability in a concentration dependent manner. A dissociation constant of about 0.14 mmol/l could be estimated. The amplitude of the single channel current was not affected by ATP-concentrations in contrast to changes in phosphorylation potential. A significant increase in the single channel current accompanying a decrease in the phosphorylation potential at constant ATP concentrations was observed. This effect might be due to a decrease of free Mg2(+)-concentration by an increase of the ADP concentration in solutions with lower phosphorylation potentials. An allosteric regulation of the ATP-dependent K+ channel dependent on the free ATP concentration together with the Mg2(+)-ADP concentration seems to be a more likely explanation than regulation by phosphorylation/dephosphorylation secondary to a breakdown of ATP. PMID- 2325138 TI - Adjusting to visual impairment. AB - Adjustment to visual impairment occurs in three phases: preimpact (following vision loss but before the person is aware of the loss), impact (realization of the loss), and acceptance (learning to work within the limitations of the impairment). The factors leading to the realization of the vision loss are important because they help the person define the event and give it meaning. Those who cannot discuss these factors have not begun to adjust. By discussing the criteria for adjustment that each person holds, nurses would be better able to design programs to help meet their goals. PMID- 2325139 TI - Impromptu teaching and a collaborative approach. Enhancing the patient's comprehension and satisfaction. AB - Although multiple studies have shown that knowledgeable patients are better able to deal with health problems and are more compliant with prescribed medical regimens, health-care providers often fail to educate patients adequately. The most commonly professed barrier to patient education is time, even though nurses spend more time with patients than other members of the health-care team. This time is usually in frequent but small segments. These small segments of time can be used for impromptu teaching, an efficient means of conveying information when a patient's learning readiness and needs are high. PMID- 2325140 TI - The neonatal fundus in maternal toxemia. AB - Fetal mortality appears to be related to the neonatal fundus findings of a generalized arteriolar spasm, together with either a serous retinal detachment or the presence of numerous superficial and deep retinal hemorrhages with "cotton wool" spots. The excellent management of maternal blood pressure does not allow changes to occur in the maternal fundus; thus, the existence of adverse factors to the fetus/newborn cannot be determined by an examination of the maternal fundus. The fundus examination of a neonate at risk is likely to be very helpful in identifying those babies who would require intensive monitoring and care, resulting in an infant mortality rate far lower than the current rate. PMID- 2325141 TI - Contact lenses in an industrial environment. PMID- 2325142 TI - AIDS lobby earns respect from cancer leaders. PMID- 2325143 TI - Cigarettes exceed Perrier's benzene level, but are not regulated. PMID- 2325145 TI - Psychoneuroimmunology: can the brain and immune system communicate? PMID- 2325144 TI - Survey finds more physicians emphasizing early detection. PMID- 2325146 TI - Intramural citations: which NIH institute has more? PMID- 2325147 TI - Glutathione S-transferase activity, sulfhydryl group and glutathione levels, and DNA cross-linking activity with chlorambucil in chronic lymphocytic leukemia. AB - Glutathione (GSH) levels and glutathione S-transferase (GST) activities were measured in the leukemia cells of 12 patients with chronic lymphocytic leukemia. Both were correlated with prior clinical exposure to alkylating agents and with DNA cross-link formation by chlorambucil in these cells in vitro. No correlation was observed between prior exposure to alkylating agents and GSH level or GST activity. An inverse correlation was observed between GST activity and cross linking by chlorambucil, which was enhanced if both GST activity and GSH level were related to cross-linking. These findings suggest that the combination of GST and GSH protects the DNA of leukemia cells from chlorambucil, but the role of this combination in clinical resistance remains to be determined. PMID- 2325148 TI - Detection of etoposide resistance by measuring DNA damage in individual Chinese hamster cells. AB - The comet assay, which measures DNA strand breakage in individual cells, was used to examine the relation between DNA damage, cell survival, and resistance to the topoisomerase II inhibitor etoposide (VP-16). Chinese hamster V79-171b cells and a VP-16-resistant subline (VPr) were exposed to VP-16 as monolayers or spheroids. The comet assay was comparable in sensitivity to the DNA precipitation and alkali unwinding assays for detecting DNA strand breaks induced by VP-16. However, unlike conventional DNA damage assays, the comet assay also indicated heterogeneity in cell response. For V79 multicell spheroids exposed to VP-16, the external cycling cells were 50 times more sensitive to killing and DNA damage than the internal noncycling cells; the comet assay indicated the fraction of cells resistant to the drug. VPr cells, which were 10 times more resistant to killing and DNA damage by VP-16 than the parent cell line, could also be identified in mixed populations with the use of this method. These results suggest that the comet assay could be useful in predicting tumor cell response to DNA-damaging agents. PMID- 2325149 TI - N-nitrosodimethylamine blood levels in patients with chronic renal failure: modulation of levels by ethanol and ascorbic acid. AB - We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male patients, 30-74 years old, who had chronic renal failure, and in five healthy control subjects (four males and one female) 31-50 years old. In the patients, we found significant (P less than .01) levels of NDMA (mean +/- SD; 201 +/- 111 ng/kg of blood), which is known to be carcinogenic in animals. Five minutes after oral administration of ethanol (0.4 g/kg of body weight), all patients exhibited a significant (P less than .01) rise in blood NDMA levels (338 +/- 125 ng/kg), suggesting continuous endogenous formation of NDMA that was unmasked by ethanol's ability to inhibit first-pass hepatic metabolism of NDMA. In five of six patients, pretreatment with oral ascorbic acid resulted in a blunting, but not statistically significant, effect on maximum blood NDMA levels after consumption of ethanol. Mean levels were 340 +/- 100 ng/kg before treatment with ascorbic acid and 237 +/- 127 ng/kg during treatment. Ethanol administration unmasks increased gastrointestinal formation of NDMA in patients with chronic renal failure. Further studies are required to confirm a possible link between endogenous NDMA formation and the increased incidence of cancer in these patients. PMID- 2325150 TI - Stochastic model for interpreting the data on loss of heterozygosity in breast cancer. PMID- 2325151 TI - Leukemia following cisplatin therapy. PMID- 2325152 TI - Comparative angiotoxic responses of avian and rodent species in vivo: implications in atherogenesis. AB - As the intrinsic susceptibility to atherosclerosis differs among several taxonomic groups, the present studies were conducted to compare the angiotoxic responses of atherosclerosis-susceptible (quail) and -resistant (rat) animals to allylamine, a selective cardiovascular toxin. Japanese quail (125-150 g) and Sprague-Dawley rats (175-200 g) were gavaged daily for 1, 7, or 20 d with allylamine HCl (0.7, 7, and 70 mg/kg) or tap water. At the ultrastructural level, subchronic exposure of quail and rats to allylamine was associated with dose- and time-dependent disruption of the structural integrity of aortas. These alterations correlated with fluctuations in the nonprotein thiol content of avian and rodent vessels. Angiotoxicity was not associated with alterations in serum cholesterol content. At all times and doses tested, quail were more susceptible than rats to the angiotoxic effects of allylamine. Although the avian sensitivity to toxic insult was greater than that of rodents, quail aortic homogenates bioactivated allylamine to a lesser extent than rat homogenates. Collectively, these results suggest that the aortic sensitivity to toxic insult in avian and rodent species correlates with their intrinsic susceptibility to vascular injury. PMID- 2325153 TI - Pulmonary carcinogenesis in rats given implants of shale oil in beeswax pellets. AB - Pellets of crude shale oil, neutral, basic, or polynuclear aromatic fractions of shale oil, or crude petroleum were implanted in the lungs of rats through a thoracotomy. The pellets had a beeswax-tricaprylin vehicle that allowed the slow release of material into the surrounding parenchyma. A dose-related incidence of lung cancer was observed with each of the materials studies. A greater risk for lung cancer was not demonstrated for crude shale oil compared to crude petroleum. PMID- 2325154 TI - Metabolism and nephrotoxicity of indan in male Fischer 344 rats. AB - Indan, a component of fuels, solvents, and varnishes, is metabolized in male Fischer 344 rats to 1-indanol, 2-indanol, 5-indanol, 1-indanone, 2-indanone, 2 hydroxy-1-indanone, cis-1,2-indandiol, and trans-1,2-indandiol. The metabolites were identified using the techniques of gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The rats treated with indan demonstrated the classic lesions of hydrocarbon-induced nephropathy. The kidney damage produced was less than that found for tetralin and other branched-chain acyclic hydrocarbons. PMID- 2325155 TI - Toxicology and carcinogenesis studies of dietary titanium dioxide-coated mica in male and female Fischer 344 rats. AB - Male and female Fischer 344 rats were fed diets containing 0, 1.0, 2.0, or 5.0% titanium dioxide (TiO2) coated mica for up to 130 wk. This dosage regimen produced no consistent or biologically important changes in survival, body weight gains, hematologic or clinical chemistry parameters or histopathology. Under the conditions of this 130 wk feeding study there was no evidence that TiO2-coated mica produced either toxicologic or carcinogenic effects at dietary concentrations as high as 5.0%. The results suggest that dietary exposure to TiO2 coated mica does not pose a significant human health hazard. PMID- 2325156 TI - Low-abundance 32-kilodalton nuclear protein specifically enriched in the central nervous system. AB - Recently, a low-abundance nuclear protein, p32/6.3, has been identified in brain tissue (Egle and Shelton: Journal of Biological Chemistry 261:2294-2298, 1986). Using a Western blot procedure, we describe its distribution in the nervous system, determine its relative enrichment in brain versus liver, kidney, and certain other tissues, and describe an isolation procedure from brain. Selective enrichment occurs in basal ganglia, diencephalon, hippocampus, cerebellum, brainstem, spinal cord, and cerebral cortex but not in retina, dorsal root ganglia, and sympathetic ganglia. Thus, enrichment is limited to areas of the central nervous system. p32/6.3 appears to be preferentially enriched in neurons, because in bulk-isolated fractions from rat grey matter it is more abundant in neuron-enriched fractions than in astrocyte-enriched fractions. p32/6.3 is approximately 20-fold more concentrated in an insoluble nuclear protein or matrix fraction from forebrain than from kidney, liver, adrenal gland, or retina. This degree of enrichment is an ancient trait, detectable in the chicken as well as mammals. PMID- 2325157 TI - Cholinergic function in cultures of mouse spinal cord neurons. AB - Cholinergic synapses formed in cultures of fetal mouse spinal cord (SC) and superior cervical ganglion (SCG) were studied using intracellular and extracellular stimulation and recording as well as immunohistochemical staining for choline acetyltransferase (ChAT). Dissociated SC neurons and SC explants exhibited cholinergic terminals on SCG and SC neurons as demonstrated by ChAT immunoreactivity. Intracellular recordings showed that cholinergic inputs to SCG neurons were relatively common and that these synaptic inputs were blocked by the nicotinic acetylcholine (ACh) receptor blocker, tubocurarine. A comparison of three preparations indicated that the incidence of cholinergic activity recorded in SCG neurons was significantly higher in co-cultures of SCG with spinal cord ventral horn (VH) neurons grown on a substrate of non-neuronal cells from cerebral cortex, than in co-cultures with VH alone or with SC and dorsal root ganglion cells. Consistency between cholinergic physiology and staining for ChAT positive terminals on SCG neuronal somata was obtained in cultures of SC explants grown with dissociated SCG. Application of acetylcholine, muscarine, and/or vasoactive intestinal polypeptide (VIP) produced slow excitation of SC neurons. Fast excitatory cholinergic interactions between SC neurons were not observed. Excitatory synaptic interactions between SC neurons were augmented by ACh or muscarine, while inhibitory synaptic interactions were diminished. Both types of synaptic modulation probably were produced by a presynaptic mechanism. Acetylcholine or muscarine affected synaptic interactions between SC neurons in only one-third of the synaptic connections tested, suggesting that the incidence of presynaptically cholinoceptive SC neurons is low in dissociated cell cultures. The experimental results show that a culture system incorporating dissociated fetal mouse SC neurons or explants of SC with sympathetic ganglion neurons expresses both nicotinic and muscarinic cholinergic function. PMID- 2325158 TI - Modification of anoxic neuronal injury by human recombinant epidermal growth factor and its possible mechanism. AB - A primary culture of cortical neurons was established from a 17-day rat embryo. Twenty-four hours after plating, the culture medium was changed to a chemically defined one, and human recombinant EGF (rEGF) was added to the medium at concentrations of 1, 10, and 100 ng/ml. Anoxic stress was exerted on the cultured neurons for 4 hr. Without anoxia, rEGF at a concentration of 10 ng/ml supported neuronal survival. When rEGF was not present in the culture medium, anoxic stress reduced neuronal density to one-tenth that of the nonanoxic group. The rEGF improved neuronal recovery from anoxia significantly, with survival dependent on rEGF dosage. Monoclonal antibody for EGF receptors canceled the effect of rEGF on survival of neurons in a dose-dependent manner. Therefore, rEGF functioned to support neuronal survival from anoxia through EGF receptors. Ontogeny of the EGF receptors was detected immunocytochemically with anti-EGF receptor antibody. About 70% of the cultured neurons were stained by the anti-EGF receptor antibody 3 days after change of medium, and immunoreactivity for EGF receptors was found to be located on the soma of neurons. Binding activity of EGF receptors was detected 5 days after change of medium with receptor binding assay and Scatchard analysis. High-affinity binding sites were detected only in neurons cocultured with rEGF (10 ng/ml) for 5 days. The data indicate that rEGF in sufficient concentration induces high-affinity sites of the EGF receptor and that EGF may have an antianoxic effect through the EGF receptors. PMID- 2325159 TI - Phosphorylation of proteins of the postsynaptic density: effect of development on protein tyrosine kinase and phosphorylation of the postsynaptic density glycoprotein, PSD-GP180. AB - The effect of development on the tyrosine kinase activity of postsynaptic densities (PSDs) has been determined. PSDs were prepared from the forebrains of rats ranging in postnatal age from 13 to 90 days and the phosphorylation of both exogenous and endogenous substrates by tyrosine kinase measured. PSDs exhibited tyrosine kinase activity at all ages examined. Phosphorylation of the exogenous substrates polyglutamyltyrosine (4:1) and [val5] angiotensin II increased twofold between days 17 and 22 and then decreased between days 30 and 90 to levels slightly lower than those present at 13 days. The phosphorylation of endogenous PSD proteins on tyrosine residues, assessed by alkali digestion of polyacrylamide gels of 32P-labelled PSD proteins and by measuring the formation of [32P] phosphotyrosine by PSDs incubated in the presence of [gamma-32P] ATP, closely paralleled the changes in total tyrosine kinase activity. Tyrosine phosphorylation of the PSD-specific glycoprotein, PSD-GP180, also showed a transient increase between days 22 and 30, although its concentration within the PSD continued to increase slowly up to 90 days. The results indicate that the tyrosine kinase activity of PSDs is developmentally regulated and that tyrosine phosphorylation of PSD proteins is limited by enzyme rather than substrate availability. PMID- 2325160 TI - Neonatal hyperthyroidism in the rat produces an increase in the activity of microperoxisomal marker enzymes coincident with biochemical signs of accelerated myelination. AB - The effect of neonatal hyperthyroidism produced by injection of tri-iodothyronine (T3) on myelination and on the microperoxisomal population of the brain was studied in young rats. Data on the lipid composition of myelin show that myelinogenesis starts earlier in treated animals. In coincidence with the early appearance of myelin, there is an increase in the population of brain microperoxisomes, indicated by the increase in the activity of two enzymes that have been shown to be located in these organelles: catalase and acyl CoA dihydroxyacetone phosphate acyl transferase. Double-label experiments using (1,2,3-3H) and (2-3H) glycerol to study the synthesis of glycerophospholipids through the dihydroxyacetone phosphate (DHAP) pathway give further support to the above-mentioned findings and suggest that there is an active participation of microperoxisomes in the synthesis of myelin lipids during the period of myelin formation. PMID- 2325162 TI - Role of nerve growth factor in oxidant-antioxidant balance and neuronal injury. II. A conditioning lesion paradigm. AB - The PC12 rat pheochromocytoma cell line is a nerve growth factor (NGF) responsive line that is protected by NGF from the toxic effects of hydrogen peroxide induced peroxidation. In part, NGF protection of PC12 cells acts through a shift in oxidant-antioxidant metabolism by the enhancement of catalase activity. When PC12 cells are used in a conditioning lesion paradigm to study the effects of an initial sublethal peroxidative insult on subsequent responses to injury, a low dose conditioning lesion protects even in the absence of NGF. The magnitude of the protective effect exerted by the conditioning lesion, however, is augmented in the presence of NGF, since a significant cytoprotective effect is observed over a wider range of H2O2 concentrations. Neuronal injury due to treatment with a high dose of H2O2 (5 mM) has a cytotoxic effect that cannot be prevented by NGF treatment and is, in itself, not conditioning in nature. This in vitro model system lends itself to the development of explanations regarding the salutory effects of conditioning lesions at the molecular level. PMID- 2325161 TI - Role of nerve growth factor in oxidant-antioxidant balance and neuronal injury. I. Stimulation of hydrogen peroxide resistance. AB - The nerve growth factor protein (NGF) regulates neuronal cell death during the development of embryonic sensory and sympathetic neurons in the peripheral nervous system (PNS). NGF protects the rat pheochromocytoma line PC12, a useful model of NGF responsive peripheral neurons, from hydrogen peroxide, which interacts with ferrous iron to generate hydroxyl radicals. Exogenous catalase provides protection, whereas superoxide dismutase (SOD) has no effect on neuronal survival when PC12 cells are challenged with hydrogen peroxide. NGF treatment of PC12 cells increases the activity of catalase. NGF protection from hydrogen peroxide is partially abolished by aminotriazole (Az), a low molecular weight catalase inhibitor. Taken together, these data are consistent with the hypothesis that NGF protects from peroxidative events and consequent cell death via an induction of free radical detoxifying mechanisms, such as catalase activity. PMID- 2325163 TI - A small subpopulation of progesterone receptor-containing neurons in the guinea pig arcuate nucleus projects to the median eminence. AB - In female guinea pigs, a combination of retrograde tracing and immunofluorescence for progesterone receptors (PR) was applied to determine if PR-immunoreactive (PR IR) neurons in the arcuate nucleus (AR) send their axons directly to the median eminence (ME). Axonal projections to the ME were studied by different techniques using fluorescent dyes. From 31 adult animals, ovariectomized and primed by estradiol, small deposits of Lucifer Yellow (LY) were made on the cut surface of the ME, either by direct application of LY crystals or by iontophoresis. These techniques were carried out on excised mediobasal hypothalamus maintained in vitro and allowed visualization of AR perikarya projecting to the ME after dye diffusion in the severed axons. In another group of ten immature animals primed by estradiol, Granular Blue (GB) was injected in the jugular vein. Blood-borne GB was taken up in the ME by intact nerve endings and retrogradely transported to the perikarya of origin. PR-IR neurons and perikarya filled with LY or retrogradely labeled by GB were intermingled with each other throughout the rostrocaudal extent of the AR. Double-labeled cells, displaying PR immunoreactivity and dye labeling, were observed consistently, but their number was small. This result demonstrates that some AR neurons sending axonal projections to the ME are target cells for progesterone. As the majority of PR-IR neurons in the AR do not project to the ME, it is suggested that most PR-IR neurons present in this nucleus form local circuit projections or project to distant areas of the central nervous system. PMID- 2325164 TI - Vasoactive intestinal peptide: a neurotrophic releasing agent and an astroglial mitogen. AB - Vasoactive intestinal peptide (VIP) increases neuronal survival in dissociated spinal cord cultures during a critical period of development. In the present study, two mechanisms contributing to this action of VIP have been observed: 1) VIP was shown to be a secretagogue for neuron survival-promoting activity; and 2) VIP was found to be an astroglial mitogen. A high molecular weight substance (greater than 30 kDa), which increased neuronal survival in tetrodotoxin (TTX) treated spinal cord cultures, was detected in the medium from nonneuronal cells incubated for 1 hr with 0.1 nM VIP. In addition, 3H-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry were used to show that a 5 day treatment with (VIP) increased astroglial mitosis. This effect was specific for astroglia, as silver grain-positive cells not exhibiting GFAP immunoreactivity did not increase in number after VIP treatment. The dual action of VIP may regulate glial-derived trophic substances that are important for neuronal survival during the course of development. PMID- 2325165 TI - Rat dopamine beta-hydroxylase: molecular cloning and characterization of the cDNA and regulation of the mRNA by reserpine. AB - A number of cDNA clones for rat dopamine beta-hydroxylase (DBH) were isolated from a rat pheochromocytoma tumor cDNA library. The 2445 nucleotide sequence revealed a single open reading frame of 1860 nucleotides and a 3' untranslated region containing two polyadenylation addition signals. The cDNA coded for a 620 amino acid protein of 69,883 daltons. Six potential glycosylation sites and one potential phosphorylation site were identified. Amino acid residues likely to be involved in the active site of DBH and in copper ligand binding were identified. The N-terminal 42 amino acids appeared to constitute a typical but unusually long signal sequence. Hydropathy analysis indicated that this N-terminal region contained the only extensive hydrophobic domain and thus constituted the only obvious potential membrane attachment site. Northern analysis detected two mRNA species of 2.5 and 2.7 kb. The relative abundance of the 2.7 vs. 2.5 kb mRNAs was differentially regulated in PC12 cells and adrenals. DBH mRNA levels were induced in vivo in rat adrenals upon treatment with reserpine. PMID- 2325166 TI - Rescue of basal forebrain cholinergic neurons after implantation of genetically modified cells producing recombinant NGF. AB - Mouse 3T3 fibroblasts were genetically modified by transfection with a mammalian expression vector containing the rat beta-nerve growth factor (NGF) gene. The transfected cell line, designated 3E, contains several hundred copies of the rat NGF gene and secretes high levels of biologically active NGF. Pieces of collagen gel containing the NGF-secreting 3E cells were grafted to the brains of unilaterally fimbria-fornix-lesioned rats. Grafts of the genetically modified NGF producing cells rescued axotomized basal forebrain cholinergic neurons and significantly reduced cholinergic cell death in the medial septum as compared with rats treated with grafts of the parental 3T3 cells. Grafted fibroblast cells were detected, and rescue effects were noted up to 6 weeks after grafting. Local effects of NGF secreted by grafted cells were also seen at the gel-brain border in the form of sprouting acetylcholinesterase immunoreactive host cortical fibers. We suggest that implantation of genetically modified cells producing NGF may have therapeutic applications in rescuing damaged central cholinergic neurons in senile dementia of the Alzheimer type as well as in providing trophic support for chromaffin tissue grafts in Parkinson's disease. PMID- 2325167 TI - Complex craniomaxillofacial trauma: evolving concepts in management. A trauma unit's experience--1989 Fraser B. Gurd lecture. PMID- 2325168 TI - Pediatric Chance fractures: association with intra-abdominal injuries and seatbelt use. AB - Seven cases of Chance fractures of the spine in children are presented, with their association to intra-abdominal injuries secondary to seatbelt use. A discussion and review of the literature suggest an increasing frequency of this particular injury with a high association given the clinical sign known as the "seatbelt sign." Also reviewed is the association of intra-abdominal injuries secondary to seatbelt restraints, and particular attention is paid to the concurrence of intra-abdominal injury with Chance fractures of the spine. The unique features of the pediatric anatomy in relation to the design of the adult seat restraint as it relates to the vertebral fracture and intra-abdominal injuries are noted. A review of the literature discusses the development of a classification for this flexion-distraction type of vertebral injury, and supports our experience of the increasing frequency of these particular injuries with increasing seatbelt use. PMID- 2325169 TI - Improving the record of patient assessment in the trauma room. AB - To facilitate clinical research at the Regional Trauma Unit at Sunnybrook Medical Centre in Toronto, it was decided to attempt to improve the quality and quantity of clinical patient information obtained at initial assessment in the Trauma Room. Standardized patient forms were introduced to replace the narrative record, including forms for the Trauma Team Leader, Anesthesia, General Surgery, Neurosurgery, Orthopedic Surgery, and Plastic Surgery. These forms were evaluated in this study which compared 100 charts generated before introduction of the forms to 100 charts generated following the implementation of the forms, with respect to certain items of patient demography and clinical condition. There was a statistically significant improvement in amount of information collected and in a format which facilitates data storage and retrieval. This, in turn, establishes an excellent standardized database for clinical trials in trauma care. PMID- 2325170 TI - The relative influence of alcohol and seatbelt usage on severity of injury from motor vehicle crashes. AB - Seatbelt usage has been consistently documented to decrease mortality and injury severity from motor vehicle crashes (MVC); however, conflicting results are available comparing mortality and injury severity, and blood alcohol positivity. Prospective testing on all MVC admissions showed that 51.5% of the non-belted, and 22% of the shoulder-belted drivers had a positive blood alcohol content (p less than 0.001). A comparison of belted and non-belted MVC drivers revealed a significantly higher mean length of stay (LOS) (p less than 0.05) and Injury Severity Score (ISS) (p less than 0.01) for the non-belted drivers. A comparison of groups positive and negative for blood alcohol revealed no significant differences in LOS or ISS, suggesting that these parameters are related to seatbelt use and not alcohol consumption. PMID- 2325171 TI - Blood alcohol testing of motor vehicle crash admissions at a regional trauma unit. AB - Motor vehicle crashes remain a leading cause of death and injury in the industrialized world. Alcohol consumption is implicated as a major factor in fatal motor vehicle crashes (MVCs), but only poor estimates of blood alcohol concentrations among nonfatally injured crash victims are available. A 3-year study was undertaken at a Regional Trauma Unit to determine the demographics, injury severity, and alcohol positivity of motor vehicle crash victims. Between August 1, 1986 and July 31, 1989, 825 motor vehicle crash victims were available for study; 368 drivers were admitted to the unit within a period of 4 hours. Of 715 patients tested for alcohol, 31.0% were positive. A total of 333 drivers were tested for blood alcohol; 128 (38.4%) were positive. The mean blood alcohol concentration (BAC) at admission for the drivers was 145.6 mg/100 ml; the estimated mean BAC at crash was 180.9 mg/100 ml. The mean age of BAC positive drivers was 31.4 years, compared to a mean age in the BAC negative drivers of 35.2 years (p less than 0.02). Male patients represented 76.6% of the drivers, yet represented 83.6% of the BAC positive drivers (p less than 0.05). There was a marked seasonal variation in BAC positivity, with 46.1% of drivers positive during the summer months. Alcohol appears to be a significant factor in nonfatal MVCs. PMID- 2325172 TI - Heat loss in exposed volunteers. AB - Hypothermia is a common complication of major surgery and trauma. We studied this problem using Heat Flux Transducers to directly measure heat exchange between seven exposed volunteers and the environment. Heat exchange by radiation and convection was measured from the anterior chest wall and by conduction, between the back and a thermal mattress (CSZ, Blanketrol II). We determined the coefficients for: radiation = 6.6; convection = 8.3 square root of v; combined radiation and convection = 9.7; conductance = 41, all expressed in W/m2.degrees C. The clinical significance of these results is that heat loss, by radiation and convection alone, is 10 W/m2.degrees C. However, heat production under anaesthesia is only 40 W/m2, so a temperature gradient of greater than 4 degrees C between the skin and environment will cause more heat to be lost than is produced. The thermal mattress can supply 41 W/m2.degrees C, effectively doubling heat production. PMID- 2325173 TI - Trauma outcome analysis of two Canadian centres using the TRISS method. AB - In this retrospective study, the TRISS method of trauma care analysis is used to compare trauma care at the Hamilton General Hospital (HGH) and the Ottawa Civic Hospital (OCH) with the standards reported in the Major Trauma Outcome Study (MTOS). A total of 274 adult patients with multiple-system injuries were studied; their demographic data, Trauma Scores (TS) on arrival to the Emergency Room, and Injury Severity Scores (ISS) were reviewed. The TRISS scores and Z and M statistics were then calculated. In the Hamilton group, 106 consecutive patients from April through July 1987 were studied. The majority of patients (72%) were male, and the median age was 26 years. The majority of patients (96.2%) sustained blunt trauma, with motor vehicle accidents (MVA) being the most common (76.4%) mechanisms of injury. Fifty-four (51%) of the patients were transferred from outlying hospitals. The Z and M statistics were -0.05 and 0.92, respectively. In the Ottawa group, 168 consecutive patients from April 1987 through October 1988 were studied. The majority of patients (73%) were male, and the median age was 39 years. Blunt trauma accounted for the majority (91.7%) of injuries, with MVAs being responsible for 58% of injuries. Most patients (63.5%) were transferred from regional hospitals. The Z and M statistics were 1.20 and 0.56, respectively. We conclude that the survival statistics of trauma patients treated at both centres are comparable to those of trauma patients in the MTOS. PMID- 2325174 TI - An early surgical approach to burns in the elderly. AB - This study evaluates our experience with an early surgical approach in 52 consecutive patients over the age of 65 years. Eighteen patients were taken to the operating room for early excision (less than 7 days postburn) and 34 patients were excised after 7 days (late excision). The early and late excision groups were matched for age, sex, and size of burn. In survivors, the early excision group had a 32% reduction in mean hospital stay (p less than 0.05). In addition, early surgical excision resulted in fewer episodes of sepsis and pneumonia (p less than 0.05). However, there was no significant improvement in age- and burn size-specific survival in the early excision group (p greater than 0.05). We conclude that elderly patients represent a high-risk population, and that early surgical excision results in fewer episodes of infection and a reduction in hospital stay but does not significantly improve survival. PMID- 2325176 TI - Flexion-distraction injuries of the lumbar spine and associated abdominal trauma. AB - Recent experience with flexion-distraction injuries of the lumbar spine associated with blunt abdominal trauma and the use of a lap belt alone has caused us to review our experience over the last 7 years. Eighteen patients were identified, with an average age of 22 years, and an average followup of 34 months. Fifteen were involved in motor vehicle accidents, with 11 being single vehicle accidents. Of note, 12 of the 15 were rear seat passengers with lap belts only. Twelve patients suffered abdominal injury, seven requiring operative intervention, mainly for hollow viscus injury. In three patients, a delay of 24 hours or more occurred before recognition of intra-abdominal pathology requiring surgical therapy. One patient had an unrecognized spinal fracture for 2 weeks after abdominal surgery for a perforated viscus. The spinal injury was carefully assessed and analyzed for prognostic factors. Six were graded excellent, five good, four fair, and one poor. One case of paraplegia associated with avulsion of the spinal cord from distraction is reported. Prognostic factors included the amount of facet joint involvement and the degree of initial kyphosis. Those having greater than 17 degrees of kyphosis had a poor prognosis. Early recognition of the constellation of injuries involving the spine and abdomen associated with the use of the lap belt is recommended with surgery to the spinal fracture as outlined. PMID- 2325175 TI - Endoscopic guided percutaneous tracheostomy: early results of a consecutive trial. AB - Percutaneous tracheostomy is increasingly being used for patients needing prolonged ventilatory support. The purpose of this study was to assess the feasibility of widespread application of endoscopic guided percutaneous tracheostomy. Sixty-one consecutive ICU patients requiring prolonged mechanical ventilation underwent bedside endoscopic guided percutaneous tracheostomy. Using a modified Ciaglia technique, a #6-10 tracheostomy tube was introduced between the second and third tracheal rings. Bronchoscopic transillumination facilitated identification of the appropriate tracheostomy site, and verified satisfactory placement of dilators and tracheostomy tube. There was one procedure-related death due to arrhythmia. Procedure-related complications included (n = 7): bleeding (controlled with local pressure), two infections, two cuff tears, and two obstructions of the tracheal tube. The tracheostomy was eventually removed in 13 patients. Bronchoscopic evaluation of three patients at 4 months post tracheostomy removal was normal and there has been no clinical evidence suggestive of tracheal stenosis in the remaining ten extubated patients. There was a 50% reduction in cost when compared to operative tracheostomy. Percutaneous tracheostomy is a simple, safe, cost-effective bedside procedure for critically ill ventilator-dependent patients. Endoscopic guidance appears to increase the safety of this procedure and may prevent complications of pneumothorax, subcutaneous emphysema, and paratracheal false passage previously reported with blinded percutaneous methods. PMID- 2325177 TI - Cervical spine injuries in children. AB - Cardiorespiratory arrest occurring immediately after multiple injuries is usually assumed to be due to severe cerebral injury, acute hemorrhage, or airway obstruction. We have identified a group of 19 children (mean age, 6.3 years) who presented with absent vital signs (VSA) or severe hypotension, unexplained by blood loss, where these findings were caused by injury to the high cervical spine and cord, demonstrated either by X-ray or postmortem examination. Fourteen had radiologic evidence of injury to the spine between C1 and C3. In two patients the bony injury was at the C6-7 level, while in two patients the cervical spine X-ray was normal. Eighteen of the 19 children were initially resuscitated but died from a combination of hypoxic/ischemic encephalopathy and cerebral injury. Sixteen patients underwent postmortem examination and in 13 there was evidence of cord laceration, up to and including cord transection. These findings demonstrate a distinct pattern of "juvenile" cervical spine injury involving the high spine and cord which results in either apnea and cardiorespiratory arrest, or severe hypotension. This previously unrecognized cause of cardiorespiratory arrest should be considered in all children presenting with VSA after multiple trauma, even when there is no apparent radiologic abnormality of the cervical spine. PMID- 2325178 TI - Injury surveillance using hospital discharge abstracts coded by external cause of injury (E code). AB - Current knowledge of the patterns of injury in the United States derive principally from mortality statistics that constitute less than 0.1% of all injuries reaching medical attention. There presently exists no national system for the surveillance of nonfatal injuries. To illustrate the usefulness and feasibility of conducting injury surveillance using E-coded hospital discharge data, we examined the surveillance data from the Massachusetts Statewide Childhood Injury Prevention Program. By using E-coded hospital discharge data, we increased the number of cases available for analysis by 40-fold over deaths, and we were able to describe the epidemiologic characteristics of the important causes of nonfatal childhood injuries. We therefore propose the development of a national injury surveillance system based on the Uniform Hospital Discharge Data Set coded by both the nature of the injury (N Code) and external cause (E Code). PMID- 2325179 TI - Lower infection rate after interlocking nailing in open fractures of femur and tibia. AB - Between 1975 and 1987 91 patients with Types I and II open lower extremity fractures (66 tibia and 25 femur) have been treated surgically with interlocking nailing at the I University Clinic of Traumatology, and the Trauma Department of Wilhelminenspital, Vienna. Our infection rate of 1.2% was found to be lower than figures cited in the literature. Conscientious indication of the interlocking nail in these circumstances cannot claim all the credit for these results, the appropriate preoperative management with preventive antibiotics together with excellent operative technique have to be taken into consideration as well. Reviewing these results, we have adopted the opinion that the interlocking nail, when selectively used in the hands of an expert, can be recommended not only in closed fractures but also in Types I and II open fractures of the femur and tibia, provided that the special principles of treatment in a particular case are not neglected. PMID- 2325180 TI - Pressure waves caused by high-energy missiles impair respiration of cultured dorsal root ganglion cells. AB - High-energy missile extremity impact causes short-lasting pressure waves which traverse the body with a velocity close to that of sound in water. In order to elucidate mechanisms for distant damage in a living body to the peripheral and central nervous system, a model system was designed aimed to create pressure waves with amplitudes, frequency spectrum, and duration fairly comparable to those recorded in situ. Our model system enabled exposure of tissue cultures of dorsal root ganglion (DRG) and endothelial cells under strictly controlled conditions to a burst of oscillating pressure waves and to determine possible influence on oxygen consumption. Oscillating pressure waves caused by high-energy missile impact (velocity 1,200 m/s) reduced the oxygen consumption by more than 80%. However, in spite of this drastic, acute effect the ganglion cells and the feeder layer cells did not reveal any immediate plasma membrane dysfunctions as revealed by cytoplasmic uptake of Evans blue protein marker complexes. It is concluded that pressure waves fairly similar to those demonstrable in vivo in the vicinity of the peripheral and central nervous system after high-energy missile extremity impact in pigs reduce the respiration of DRG cells and endothelial cells in culture. The mitochondrial impairment is not associated with concomitant plasma membrane dysfunction for macromolecules. Nerve cells seem to be more vulnerable than the other type of cultured cells examined. PMID- 2325181 TI - Non-contiguous spinal fractures. AB - A retrospective review of 817 spinal fracture patients revealed a 6.4% (52/817) incidence of non-contiguous spine fractures. Seventy-three per cent of the non contiguous injuries were comprised of combinations of injuries in the cervical and thoracic regions or in the thoracic and lumbar regions. Forty-five per cent of fractures were a combination of compression fractures, 40% a combination of a compression fracture and a major spine fracture (i.e., one more likely to cause a neurologic deficit), and 15% a combination of major fractures. PMID- 2325182 TI - Open pelviperineal trauma. AB - The authors present their results in the management of 48 patients with complex pelviperineal injuries treated at the Surgical Emergency Ward of the University of Sao Paulo School of Medicine General Hospital. The distinct factors influencing the morbidity and mortality rates are discussed as well as the importance of an aggressive treatment in the initial approach of these patients. The following steps are virtually essential for the achievement of results comparable to those presented in the present protocol: exhaustive irrigation of the perineal wound with saline solution followed by surgical debridement and removal of all devitalized areas, maintenance of the wound open, early maturation transverse colostomy with total fecal flow diversion, periodic surgical revisions at intervals of 24 to 72 hours, large doses of antibiotic therapy, nutritional support with full parenteral feeding, and appropriate management of bone injuries and skin grafts. Adopting of measures proposed in this protocol yielded a decrease in mortality rate from 70% to 31.5%. PMID- 2325183 TI - A case of heterotopic transplantation after bilateral traumatic above-knee amputations. AB - This paper describes a case in which a young woman's two lower limbs were crushed and amputated from the upper part of the thighs by a train. She was in serious hypovolemic shock at the time. With rapid infusion of intravenous fluids, she recovered from shock quickly, avoiding acute renal failure and ARDS. Heterotopic transplantation was performed. Two years later, the limb which had undergone heterotopic transplantation had partly restored function. PMID- 2325184 TI - Pancreaticoduodenectomy for trauma: delayed reconstruction: a case report. AB - Experience and success with packing, resuscitation, and re-exploration for severe traumatic liver injury stimulated application of this concept to more complicated problems. In the case presented, these principles were utilized in managing a combined major hepatic and pancreaticoduodenal disruption. We emphasize stabilization, temporization, and delayed reconstruction. PMID- 2325185 TI - Isolated bilateral renal artery thrombosis: an unusual consequence of blunt abdominal trauma--case report. AB - Bilateral renal artery thrombosis with anuria following blunt abdominal trauma is distinctly unusual. We report a 16-year-old female in whom emergency revascularization with a primary reimplantation on the right and a hypogastric artery interposition graft on the left was performed following angiographic documentation of bilateral renal artery occlusion. Excellent renal function was demonstrated bilaterally at 7 weeks. Bilateral renal revascularization is feasible in the acute setting and can yield excellent results. PMID- 2325187 TI - Tuberculosis 1990. PMID- 2325186 TI - Fibrin glue and hemostasis in liver trauma: a case report. AB - We have used fibrin glue to control non-arterial hemorrhage from major liver lacerations in two patients with excellent results. It is an ideal biologic hemostatic agent. Fibrin glue uses none of the body's intrinsic clotting factors and can be prepared from commonly available products in minutes. PMID- 2325189 TI - An unusual case of pulmonary emboli. AB - The authors present an interesting case of pulmonary embolus serendipitously diagnosed during an evaluation for a presumed metastatic pulmonary nodule. PMID- 2325188 TI - Hilar and mediastinal adenopathy in sarcoidosis as detected by computed tomography. AB - CT of the chest was performed in 25 patients with chest radiographs suspicious for hilar or mediastinal adenopathy, who subsequently proved to have sarcoidosis. In each case, CT detected more extensive adenopathy than suspected on chest radiographs. Adenopathy greater than 1.0 cm was present in the right paratracheal and pretracheal regions in all cases. Adenopathy was also frequently seen in the hilar (92%), anteroposterior window (88%), subcarinal (64%), anterior mediastinal (48%), and posterior mediastinal (16%) lymph node groups. The adenopathy occurred in multiple and varying combinations without a consistent identifiable pattern suggestive of sarcoidosis. It is concluded that while CT detects adenopathy more consistently, it does not offer a clear advantage over chest radiography in confirming a diagnosis of mediastinal and hilar involvement by sarcoidosis. PMID- 2325190 TI - Pleural cryptococcosis. AB - Pleural infection by Cryptococcus neoformans is uncommon and when present typically occurs in the immunocompromised host. We report two renal transplant patients who developed pleural cryptococcosis. PMID- 2325192 TI - Sterilization of syringes and needles for immunization programmes using a pressure cooker. AB - Pressure cookers are being widely used for sterilizing equipment in small clinics and hospitals and under 'field conditions' in developing countries, especially in India. In the literature there is no report on testing of pressure cookers (PC) to determine if they sterilize adequately. The use of PC for a 15-min 'holding time' after steam starts to emanate from under the weight is quite satisfactory by standard efficacy testing methods for autoclaves. PMID- 2325191 TI - The in-vitro and ex-vivo effects of chloroquine sulphate on platelet function: implications for malaria prophylaxis in patients with impaired haemostasis. AB - Platelet aggregation responses were studied in platelet-rich plasma from six healthy volunteers before and 2 and 6 h after ingestion of 600 mg chloroquine sulphate. Apart from a mild reduction in height of aggregation response to 1 microgram ml-1 collagen 2 h post-drug ingestion (mean percentage of pre-drug values +/- s.e.m. = 87.8% +/- 4.0%; P = 0.04), no significant differences were observed in platelet responses to ADP (1 and 5 microM) or collagen (1 and 4 micrograms ml-1) at 2 or 6 h post-chloroquine compared to the pre-drug values. In vitro, drug concentrations approximately 1000 times greater than those used therapeutically were required for 50% inhibition of platelet aggregation and ATP release in response to 5 microM ADP, 1 microgram ml-1 collagen and 4 micrograms ml-1 collagen (IC50 concentrations +/- s.e.m. for inhibition of aggregation = 98.5 +/- 3.7, 53.5 +/- 56.4 and 113.0 +/- 6.2 mg l-1 respectively; IC50s +/- s.e.m. for inhibition of ATP release = 0.9 +/- 0.2, 14.7 +/- 4.0 and 23.0 +/- 5.3 mg l-1 respectively). These data provide no cause for concern in using chloroquine for malaria prophylaxis in patients with impaired haemostasis. PMID- 2325193 TI - Transmission of diarrhoea in two crowded areas with different sanitary facilities in Dhaka, Bangladesh. AB - To determine the importance of water-borne and water-washed transmission of diarrhoea we compared the degree of contamination of children's hands and drinking water with their diarrhoeal morbidity. Diarrhoeal incidence in 137 children aged 1-6 years was obtained through fortnightly home visits during the calendar year 1985. Bacterial contamination of hands and drinking water was assessed semi-quantitatively by direct contact using agar-coated slides incorporating a selective medium permitting growth of Enterobacteriaceae (Hygicult, Orion Diagnostica, Finland). Results were expressed as 2-day mean log of colony forming units per gram (cfu/g). Children were studied in two densely populated urban areas: 56 children in one area with latrines and tubewells and 81 children in the other without such facilities. Mean diarrhoea attack rates were lower in the better sanitary area (2.5 vs 3.2, P less than 0.05) as were mean log levels of water contamination (3.1 cfu/g vs 4.3 cfu/g, P less than 0.001). There was no significant correlation between water contamination and diarrhoeal incidence on an individual basis. However, in both areas diarrhoea incidence was significantly correlated with the degree of contamination of hands. After adjusting for age the risk of diarrhoea increased significantly for children with more contaminated hands in the unimproved area. This relationship strongly supports the promotion of handwashing as a method of controlling diarrhoeal diseases and, by implication, the greater importance of water quantity compared to quality. PMID- 2325194 TI - Testing for the random occurrence of sickle cell disease in a study of 100,000 Jamaican newborns. AB - In a screening programme for sickle cell haemoglobinopathies at a maternity hospital in Kingston, Jamaica, 100,000 newborns were screened with the detection of 315 cases of SS disease, and 201 cases of SC disease. There was no upward or downward trend in the frequency of SS or SC births during the screening programme. The sequence numbers of the SS and SC births were analysed to examine whether these cases were randomly distributed among the 100,000 newborns. The occurrence of SS births seems to accord well with the random model but there was an excess of very long intervals between SC births. PMID- 2325195 TI - Leptospires in the whistling frog (Eleutherodactylus johnstonei) on Barbados. AB - Two groups of whistling frogs (Eleutherodactylus johnstonei) comprising 99 and 117 animals were examined for leptospiral infection. Group I animals were caught in 14 areas of Barbados, and Group II animals in seven areas of suburban Bridgetown. Leptospires were isolated from the kidneys or body fluid of six frogs in Group I and the kidneys of 3 frogs in Group II. Two of the Group I isolates died out; the others were identified as bajan (a new serovar in the Australis serogroup) (6) and bim (Autumnalis) (1). The macerated body tissues and fluid of Group I frogs were put into phosphate buffered saline and examined by the microscopic agglutination test using 22 antigens. The results were all negative. For the Group II frogs the methodology was altered; blood was collected onto filter paper discs and allowed to dry out before being agitated in PBS and examined by the MAT. 15/117 (12.8%) animals were positive at greater than or equal to 1:100 and 19 (16.2%) at greater than or equal to 1:50. The geometric mean titre was 179. Seventeen of the sera reacted predominantly to antigens in the Australis serogroup, and two to Pyrogenes on its own. The serological results reflected the identity of the isolates. Serovars of Australis are not known to cause illness on Barbados, but bim is the commonest cause of severe leptospirosis on the island. PMID- 2325197 TI - Bites by the white-lipped pit viper (Trimeresurus albolabris) and other species in Hong Kong. A survey of 4 years' experience at the Prince of Wales Hospital. AB - The case records of 242 snake bite victims admitted to the Prince of Wales Hospital in Hong Kong between September 1984 and October 1988 were studied retrospectively. When the snake was identified, the White-lipped pit viper (Trimeresurus albolabris) was by far the commonest species involved. In addition to local oedema and inflammation, evidence of a significant blood clotting disturbance was present in at least 10% of cases, defibrination and thrombocytopenia being the commonest findings. Since such abnormality was not always sought the true figure is likely to be higher. Three fatalities occurred, one of which was secondary to a probable White-lipped pit viper bite, one to a bite by Chinese cobra and one to a bite by Russell's viper. PMID- 2325196 TI - HIV infection in Egypt: a two and a half year surveillance. AB - From April 1986 to mid-October 1988, 19,767 blood samples from individuals of 27 Governorates in Egypt were screened for antibodies to HIV-1. Risk groups included: drug addicts, prostitutes, patients with sexually transmitted diseases or fever of unknown origin, blood or blood product recipients, patients with mental disorders, and contacts of HIV-infected persons. Sera from routine blood donors and foreigners were also tested. All samples which reacted repeatedly by commercial ELISAs were assessed by Western blot (DuPont) for confirmation. Results indicated that 139 (0.70%) of the sera produced repeatedly reactive results by ELISA. Sixty-nine of these were confirmed by Western blot as HIV seropositive. This constituted 0.35% of the total population tested. Only 26 (0.15%) of the Egyptians tested were positive and a total of seven sero-positive individuals were classified as having clinical AIDS. All Egyptian blood donors were negative. Data generated during this 2.5-year HIV serosurvey indicate that the prevalence of confirmed HIV infection in Egypt was exceptionally low, and suggest that HIV is not endemic in Egypt, since all 26 sero-positive Egyptians were linked to HIV exposure abroad. PMID- 2325198 TI - Evaluation of a primary health care programme in The Gambia. II. Its impact on mortality and morbidity in young children. AB - Mortality and morbidity in children under 5 years of age were measured in 41 villages and hamlets in a rural area of The Gambia for a 1-year period before and for a 3-year period after the introduction of a primary health care (PHC) programme into 15 of the larger villages in the area. Both infant mortality and child mortality rates fell during the post-intervention period but declines were similar in PHC and in non-PHC villages suggesting that factors such as an up grading of the Farafenni dispensary, improvements in transport and the survey itself may have played an important part in bringing about these changes. Measurements of morbidity showed a lower prevalence of diarrhoea, vomiting or severe cough in PHC villages after the introduction of the PHC programme. Introduction of the PHC programme had no significant effect on nutritional status or on vaccine coverage. Significant improvements in the health of children in the Farafenni study area have taken place during the past 5 years but the PHC programme is probably only one of the factors that have brought about these changes. PMID- 2325199 TI - Protein constituents of mosquito saliva: studies on Culex molestus. AB - The protein constituents of saliva, salivary gland extracts, haemolymph and whole body extract from the Culex molestus mosquito were compared by polyacrylamide gel electrophoresis. When developed by the sensitive silver staining technique, saliva and salivary gland extract were found to contain 15 comparable protein bands. Salivary gland extract contained additional bands, presumed to be structural proteins, and saliva contained some unique protein bands which were not present in the gland extract, possibly originating in the salivary stylet lining. Some differences were found in the protein components of salivary gland extracts prepared from mosquitoes of different ages. Salivary proteins were found to be poorly represented in both haemolymph and whole body extracts. Immunoblotting of salivary gland extract with antibody raised against pure saliva exhibited binding to at least nine protein bands indicating the potential for using salivary gland extracts in place of mosquito saliva for further studies. PMID- 2325200 TI - Adenovirus type 5 packaging domain is composed of a repeated element that is functionally redundant. AB - Previous analyses have demonstrated that adenovirus DNA is packaged into virions in vivo in a polar, left-to-right fashion. The packaging of viral DNA is dependent on cis-acting elements at the left end of the genome. In this report, we describe a genetic analysis of the sequences that are required for efficient packaging of adenovirus type 5 (Ad5) DNA. Our results demonstrate that the Ad5 packaging domain (nucleotides 194 to 358) is composed of at least five distinct elements that are functionally redundant. An AT-rich repeated sequence motif, the A repeat, is located in four of five of these regions; the fifth region is also AT rich. The efficiency of viral packaging depends on the number of individual A repeats that are present in the viral genome. The deletion of the entire packaging domain resulted in the loss of virus viability. A virus that contains a multimerized oligonucleotide corresponding to A repeat II in place of the packaging domain could package viral DNA, although with reduced efficiency compared with that of the wild-type virus. Our results also suggest that the spacing of specific sequences at the left end of the Ad5 genome are important for enhancer region function in vivo. PMID- 2325201 TI - Positive and negative regulation of the minute virus of mice P38 promoter. AB - 5' deletion mutants of the minute virus of mice P38 promoter were constructed and analyzed for transcriptional activity in vitro and in vivo. In uninfected mouse A9 cell extracts, 107 base pairs upstream of the RNA start sites are required for optimal activity. Within this region, the only readily recognizable cis-acting control elements are a GC box and a TATA box. However, in infected cell extracts, deletion of a sequence between -167 and -121, which shares homology with the 30 base-pair trans-activation region (TAR) of H-1 virus (S. L. Rhode and S. M. Richard, J. Virol. 61:2807-2815, 1987), results in a three- to fourfold decrease in transcriptional activity. Interestingly, in vivo transfection experiments demonstrate a three- to eightfold increase in transcription relative to the wild type promoter when the TAR element homology region is deleted and reveal a functional role for a CCAAT motif which lies immediately downstream of the TAR element. These results indicate both positive and negative regulation of the P38 promoter. PMID- 2325202 TI - Multigene families in African swine fever virus: family 110. AB - The genome of African swine fever virus was screened for the existence of repetitive sequences by hybridization between different cloned restriction fragments covering the viral DNA. Several sets of repeated sequences were detected in fragments located close to the DNA ends. One of these groups of repetitions involved fragments located at both ends of the genome. The remaining groups involved fragments that were located exclusively at the left end. The sequence of a 3.2-kilobase segment spanning from 7.5 to 11 kilobases from the left DNA end, which showed a complex pattern of cross-hybridizations, was determined. Two short and three long blocks of direct repeated sequences were found in this DNA region, which accounted for the hybridization results. The repeated sequences formed a family of five homologous genes with an average length of 116 codons (multigene family 110), one of which had a dimeric structure. Transcripts of the five members of the family were detected both in RNA synthesized in vitro by purified African swine fever virions and in RNA isolated at early times after infection. Comparison of the predicted protein sequences revealed a striking conservation of a cysteine-rich domain in the central part of the proteins. In addition, a highly hydrophobic NH2-terminal sequence present in all the proteins suggests that these proteins are processed through the endoplasmic reticulum. PMID- 2325203 TI - Multigene families in African swine fever virus: family 360. AB - A group of cross-hybridizing DNA segments contained within the restriction fragments RK', RL, RJ, and RD' of African swine fever virus DNA were mapped and sequenced. Analysis of these sequences revealed the presence of a family of homologous open reading frames in regions close to the DNA ends. The whole family is composed of six open reading frames with an average length of 360 coding triplets (multigene family 360), four of which are located in the left part of the genome and two of which are in the right terminal EcoRI fragment. In close proximity to the right terminal inverted repeat, we found an additional small open reading frame which was homologous to the 5'-terminal portion of the other open reading frames, suggesting that most of that open reading frame has been deleted. These repeated sequences account for the previously described inverted internal repetitions (J.M. Sogo, J.M. Almendral, A. Talavera, and E. Vinuela, Virology 133:271-275, 1984). Most of the genes of multigene family 360 are transcribed in African swine fever virus-infected cells. A comparison of the predicted protein sequences of family 360 indicated that several residues are conserved, suggesting that an overall structure is maintained for every member of the family. The transcription direction of each open reading frame, as well as the evolutionary relationships among the genes, suggests that the family originated by gene duplication and translocation of sequences between the DNA ends. PMID- 2325204 TI - Chromosomal damage induced by human adenovirus type 12 requires expression of the E1B 55-kilodalton viral protein. AB - Infection of human embryonic kidney cells with adenovirus type 12 results in the induction of damage at specific (17q21-22, 1p36, 1q21, and 1q42-43) and random sites in the cellular chromosomes. A previous study by Durnam et al. (D. M. Durnam, P. P. Smith, J. C. Menninger, and J. K. McDougall, Cancer Cells 4:349 354, 1986) indicated that the expression of viral early region 1 (E1) is sufficient for the induction of damage at band 17q21-22. In the present report we used an adenovirus type 12-adenovirus type 5 recombinant with E1A hybrid sequences as well as viruses with mutations in the adenovirus type 12 E1B genes to map adenovirus type 12 E1 functions involved in the induction of genetic damage. Our results show that the expression of the E1A proteins is not sufficient for this effect. On the other hand, mutations within the E1B 55 kilodalton protein but not the E1B 19-kilodalton protein affect the ability of the virus to induce both specific and random chromosomal damage. PMID- 2325205 TI - Autonomous expression of RTVL-H endogenous retroviruslike elements in human cells. AB - Northern (RNA) blot analysis of RNA from various human cell lines and tissues has demonstrated that elements belonging to the RTVL-H family of human endogenous retroviruslike sequences are expressed in several cell types. The highest levels of RTVL-H-related RNAs were observed in teratocarcinoma cell line NTera2D1, HeLa cells, two bladder carcinoma cell lines, and normal amniotic tissue. Expression was also observed in normal chorion and in some other cell lines. The RTVL-H transcription pattern varied among the different cell types, but several expressed a unit-length 5.6-kilobase transcript. Characterization of cDNA clones corresponding to transcripts present in NTera2D1 cells indicates that the complex transcription pattern observed in these cells is generated by the following: (i) transcription of both full-length and deleted genomic elements, which is initiated within the 5' long terminal repeat (LTR) and, in all but one case, polyadenylated in the 3' LTR; (ii) the splicing of both unit-length transcripts and transcripts from a deleted element; (iii) transcription involving solo LTR sequences; and (iv) transcription which, in one case, reads through the 3' LTR into flanking cellular sequences. Sequence data obtained from 25 cDNA clones revealed that at least 13 RTVL-H elements are expressed in NTera2D1 cells. The positions of several termination codons within the pol region are the same among nine different elements, indicating that an ancestral RTVL-H element bearing these mutations dispersed within the genome. We also found that RTVL-H expression varied among samples of amnion and chorion tissue isolated from different individuals. These findings demonstrate that regulated autonomous expression of RTVL-H sequences occurs in human cells. PMID- 2325206 TI - Severity of arthritis is predicted by antibody response to gp135 in chronic infection with caprine arthritis-encephalitis virus. AB - Antibody titers to caprine arthritis-encephalitis virus surface glycoprotein gp135 and core protein p28 in synovial fluid and serum from 35 goats infected for 3 years were compared with the histologic severity of arthritis in these animals. Anti-gp135 antibody titers in synovial fluid and serum directly reflect the severity of carpal arthritis in chronically infected goats. PMID- 2325207 TI - Rapid complementation assays measuring replicative potential of human immunodeficiency virus type 1 envelope glycoprotein mutants. AB - Rapid assays which measure the ability of mutant human immunodeficiency virus type 1 envelope glycoproteins to mediate cell-free and/or cell-to-cell transmission of virus are described. By using these assays, envelope glycoprotein mutants with varying degrees of syncytium-forming ability were tested for ability to complement viral replication in trans. As expected, mutants that dramatically affect association of the gp120-gp41 envelope subunits, CD4 binding, or membrane fusion were unable to form syncytia or to support cell-free or cell-to-cell transmission. Surprisingly, some membrane fusion-defective mutants significantly attenuated in syncytium-forming ability were able to complement viral replication. Conversely, mutations in the carboxyl terminus of gp41 transmembrane glycoprotein, although not affecting syncytium-forming ability, significantly attenuated both forms of virus transmission. These results indicate that syncytium formation is not sufficient for cell-to-cell transmission of human immunodeficiency virus type 1. Furthermore, virus transmission appears to be less sensitive to inhibition of membrane fusion than is syncytium formation. PMID- 2325208 TI - Requirement for a viral trans-acting factor encoded by brome mosaic virus RNA-2 provides strong selection in vivo for functional recombinants. AB - Interaction of specific nucleotide sequences with trans-acting proteins is intrinsic to replication of viral as well as eucaryotic genomes. Brome mosaic virus RNA-2 encodes one of the two viral proteins known to be essential for replication. (R. French, M. Janda, and P. Ahlquist, Science 231:1294-1297, 1986; P. A. Kiberstis, L. S. Loesch-Fries, and T. C. Hall, Virology 112:804-808, 1981). Transfection of barley protoplasts with wild-type transcripts of brome mosaic virus RNA-1 and RNA-3 and serial dilutions of RNA-2 transcripts possessing unaltered coding sequences but bearing mutations that greatly incapacitated replication of RNA-2 revealed that trace amounts of RNA-2 are sufficient to support replication of the viral genome. In six replicate experiments containing RNA-2 transcripts devoid of the 3' 200 nucleotides that encompass the tRNA-like structure containing the minus-strand promoter, detectable levels of progeny RNA 1 and RNA-3 and subgenomic RNA-4 were present. This showed that viral p2 protein translated from the supplied RNA-2 functioned in trans to support replication of RNA-1 and RNA-3. However, in two similar experiments, progeny RNA-2 with electrophoretic mobility indistinguishable from that of wild-type RNA-2 was seen at 24 h postinoculation. Northern hybridization (RNA blot) analysis confirmed the presence of the tRNA-like 3' terminus on these progeny RNAs, indicating that recombinational restoration of the deleted sequence had occurred. This suggests that, under certain circumstances, RNA recombination may be a rapid and frequent phenomenon. PMID- 2325209 TI - T- and B-lymphocyte responses to human immunodeficiency virus (HIV) type 1 in macaques immunized with hybrid HIV/hepatitis B surface antigen particles. AB - Recombinant human immunodeficiency virus (HIV)/hepatitis B surface antigen (HBsAg) subviral particles of dual antigenicity and immunogenicity were obtained by fusing 84 amino acids of the HIV type 1 external envelope glycoprotein within the pre-S2 part of the hepatitis B middle protein (M.-L. Michel, M. Mancini, E. Sobczak, V. Favier, D. Guetard, E.-M. Bahraoui, and P. Tiollais, Proc. Natl. Acad. Sci. USA 85:7957-7961, 1988). We now describe the humoral and cellular immune response of rhesus monkeys immunized with these hybrid particles. Macaque antisera raised by subcutaneous injections of the HIV/HBsAg particles were shown to be specific for HIV in peptide-binding assays. Moreover, we were able to generate in these vaccinated animals a T-cell-proliferative response to both parts of the hybrid particle, i.e., HIV and HBsAg. These results establish the presence of a T-cell epitope in this HIV segment, which has been shown previously (L.A. Lasky, G. Nakamura, D. H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. J. Capon, Cell 50:975-985, 1987) to be an important domain involved in the binding of the virus to its cellular receptor, the CD4 molecule. This work demonstrates the feasibility of using the HBsAg subviral particle as a carrier protein for the presentation of foreign immunogenic epitopes to the immune system. PMID- 2325210 TI - Factors determining survival after ruptured aortic aneurysm: the hospital, the surgeon, and the patient. AB - The 10-year experience of a single community was reviewed and a multivariate analysis was performed to determine the relative importance of clinical and environmental factors in mortality after ruptured abdominal aortic aneurysm resection. Ruptured aneurysms were repaired in 243 patients in six area hospitals (one university, five community) by 25 surgeons (16 vascular, 9 general). Overall, 30-day mortality was 55% (133/243). Although the mortality by hospital ranged from 44% to 68%, these differences were not statistically significant. However, significant variations occurred in the mortality rates of individual surgeons, ranging from 44% to 73%. The mortality rate for the vascular surgeons was less than that of the general surgeons, 51% versus 69% (p less than 0.05). Clinical factors were evaluated, and the most significant parameters were systolic blood pressure, presence of chronic obstructive lung disease, and history of chronic renal insufficiency. These results support the implication that the degree of specialization of the surgeon and the preexisting health of the patient are the most important determinants of survival after ruptured abdominal aortic aneurysm. The size and sophistication of the hospital appear to be less influential factors. PMID- 2325211 TI - Comparison of ejection fraction and Goldman risk factor analysis to dipyridamole thallium 201 studies in the evaluation of cardiac morbidity after aortic aneurysm surgery. AB - Associated coronary artery disease is the critical factor that influences early and late mortality after abdominal aortic aneurysm surgery. Dipyridamole-thallium 201 scintigraphy, left ventricular ejection fraction, and Goldman risk factor analysis have been suggested as preoperative noninvasive screening methods to detect significant coronary artery disease. In this series of 95 elective abdominal aortic aneurysm repairs dipyridamole-thallium 201 scintigraphy was highly predictive of the absence of perioperative cardiac morbidity (96% specificity, 44/46 normal scans, no cardiac morbidity), whereas ejection fraction (73% specificity, 31/42 normal ejection fraction, no cardiac morbidity) and Goldman risk factor analysis (84% specificity, 44/51 class I, no cardiac morbidity) were less. Furthermore, thallium redistribution on dipyridamole thallium 201 scintigraphy leading to coronary angiography identified a significant number of patients with occult coronary artery disease who required preoperative coronary revascularization (8%, 8/95) and might have remained undetected on the basis of left ventricular ejection fraction or Goldman risk factor analysis. Finally, fixed thallium deficit, which some investigators have interpreted as a low probability finding for cardiac morbidity, was associated with a higher than expected incidence of cardiac complications. Forty-six percent (7/15) of all postoperative cardiac complications (three myocardial infarctions, three ischemic events, one death) occurred in patients with abdominal aortic aneurysms with fixed deficits. This suggests that patients with fixed deficits on dipyridamole-thallium 201 scintigraphy should be considered for later "delayed" (4 hours) thallium images or coronary angiography or both. PMID- 2325212 TI - Long-term results with the above-knee popliteal expanded polytetrafluoroethylene graft. AB - Since approximately 30% to 40% of autogenous vein bypass grafts to the femoropopliteal level may occlude within 5 years of implantation, additional vein will be required for subsequent revisions. We undertook a study to determine whether the preferential use of an above-knee expanded polytetrafluoroethylene bypass graft to save vein is an appropriate option. We reviewed our experience with 114 above-knee expanded polytetrafluoroethylene bypass reconstructions. Life table analysis of primary and secondary graft patency was carried out by the method of Peto and statistically analyzed for the influence of clinical indication, runoff as determined by both preoperative and intraoperative completion arteriography, smoking, and diabetes. The 5-year primary patency rate of 57% for patients with claudication was comparable to contemporary randomized or retrospective series with below-knee autogenous vein for that indication, and it was superior to the patency rate for limb salvage. The status of the runoff vessels was an important determinant of outcome. The 59 limbs with good arteriographic runoff (2 to 3 vessels) had a markedly higher 5-year patency rate (70%) than the poor arteriographic runoff (0 to 1 vessels) group (30%). Continued cigarette smoking and diabetes mellitus also appeared to affect adversely primary graft patency in our hands. Our data support the use of preferential above-knee expanded polytetrafluoroethylene grafts in patients with good angiographic runoff. This approach does not appear to prejudice the limb against secondary revisionary procedures or the use of a new autogenous graft, if required. PMID- 2325213 TI - Influence of vein size (diameter) on infrapopliteal reversed vein graft patency. AB - We reviewed 239 infrapopliteal reversed greater saphenous vein graft bypasses placed for critical ischemia over a 7-year period to determine the influence of vein diameter on graft patency and limb salvage. Grafts were assigned to four groups based on the minimum external diameter measured during operation: less than 3.0 mm, n = 18; 3.0 mm, n = 59; 3.5 mm, n = 67; and greater than or equal to 4.0 mm, n = 145. A pattern of increasing graft patency and limb salvage among the four groups was noted as the minimum external diameter increased from less than 3.0 mm to greater than or equal to 4.0 mm. When compared to the larger grafts greater than or equal to 4.0 mm, primary graft patency was significantly lower both for less than 3.0 mm grafts (0% for less than 3.0 mm vs 65% for greater than or equal to 4.0 mm at 3 years, p less than 0.001) and for long (greater than 45 cm) 3.0 mm grafts (38% for long 3.0 mm vs 75% for greater than or equal to 4.0 mm at 2 years, p less than 0.005). All 3.5 mm and short (less than 45 cm) 3.0 mm grafts had patency rates similar to greater than or equal to 4.0 mm veins. Thus long 3.0 mm and all less than 3.0 mm reversed saphenous vein grafts should be considered at high risk for failure. Veins with fibrotic, thick-walled segments identified during operation (n = 19) had patency rates significantly lower than nonfibrotic veins (n = 270; p less than 0.01), and this may play a role in the failure of some less than 3.0 mm minimum external diameter vein grafts. PMID- 2325214 TI - Race as a risk factor in the severity of infragenicular occlusive disease: study of an urban hospital patient population. AB - We retrospectively studied the arteriograms of 135 men admitted for evaluation of lower extremity ischemia to examine whether race influences the severity of infragenicular occlusive disease. The scoring system prepared by the Ad Hoc Committee on Reporting Standards for the Society for Vascular Surgery and the International Society for Cardiovascular Surgery was used to grade the severity of stenosis in each of the upper, middle, and lower thirds of the anterior and posterior tibial and peroneal arteries (collectively called "infragenicular" arteries). The patients were divided into two groups: 83 blacks (140 arteriogram limbs) and 52 whites (87 arteriogram limbs). Disease severity scores between the groups were compared, and the existence of five known risk factors for atherosclerosis were considered for poststratification adjustment. Results showed that higher disease scores, indicating more severe disease, were found in the black population in every segment of the infragenicular arteries. The mean (+/- SE) score for all the infragenicular segments in blacks was significantly higher than that in the whites (2.08 +/- 0.05 vs 1.57 +/- 0.06, p less than 0.001). The black and white groups were comparable in terms of age (65.2 vs 64.6 years), prevalence of diabetes (20% vs 25%), smoking history (93% vs 90%), and hypercholesterolemia (51% vs 63%). Hypertension was more prevalent among the black patients (51% vs 27%, p less than 0.001). When only the non-hypertensive patients in both groups were considered, however; the mean severity score was still significantly higher in blacks (2.10 +/- 0.06 vs 1.42 +/- 0.06, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325215 TI - Penetrating extremity trauma: identification of patients at high-risk requiring arteriography. AB - Indications for arteriography in patients with penetrating trauma to the extremities remain controversial. Some clinicians have recommended universal use of arteriography, whereas others prefer to rely on physical findings alone. To better define our indications for contrast studies, we reviewed clinical data on 306 patients (349 extremities) with penetrating trauma who were admitted during a prior 2-year period (1985 to 1987). Injuries were caused by stab wounds in 50 (14.3%) extremities and by gunshot wounds in 299 (85.7%) extremities. Twenty seven of the 50 stab wounds (54%) required urgent exploration based on physical findings, whereas 23 underwent arteriography. None of these studies showed unsuspected arterial injury. Twenty-nine of 299 gunshot wounds (9.7%) underwent mandatory exploration, and arteriograms were performed on 270 extremities; findings in 30 studies (11.1%) were positive for unsuspected arterial injuries. Gunshot wounds were categorized according to location and number of arteriograms with positive results. Arteriograms of lateral thigh and upper arm injuries resulted in no positive outcomes. Positive study results were recorded in 22.9% of calf injuries, 20% of forearm and antecubital injuries, 9.5% of popliteal fossa injuries, 9.0% of medial and posterior thigh injuries, and 8.3% of medial and posterior upper arm injuries. We recommend arteriography for penetrating injuries to these high-risk areas. However, clinical evaluation alone is accurate for identification of arterial trauma with lateral thigh or upper arm wounds and stab wounds to the extremities. PMID- 2325216 TI - Magnetic resonance imaging of acute occlusive intestinal ischemia. AB - The mortality of acute superior mesenteric artery occlusion and mesenteric infarction remains high, in part because of the failure to identify the patients with the disorder. A reliable noninvasive diagnostic study may facilitate earlier definitive diagnosis and therapy. Proton magnetic resonance imaging may offer a noninvasive diagnostic alternative. We examined this possibility by using an experimental rabbit model of acute superior mesenteric artery occlusion in this study. Animals were scanned 1 hour after the ischemic insult. Relative intestinal wall signal intensity was increased in experimental (ischemic) animals when compared to sham operated controls on T2-weighted (4.35 +/- 0.5 vs 2.57 +/- 0.31, p less than 0.02) and proton spin density-weighted images (2.1 +/- 0.2 vs 1.4 +/- 0.21, p less than 0.05). Significant increases in image intensity were found on T2-weighted and proton spin density images when compared to control animals. Differences between groups could be further highlighted after the administration of a paramagnetic contrast agent gadolinium diethyltriamine pentacetic acid on T1 weighted images. The data from this preliminary study demonstrate that proton magnetic resonance imaging may be used to discriminate between ischemic and nonischemic small intestine. This noninvasive tool may someday become clinically useful to enhance our diagnostic capabilities when a diagnosis of acute superior mesenteric artery occlusion is being entertained. PMID- 2325217 TI - The role of sclerotherapy as an adjunct to Unna's boot for treating venous ulcers: a prospective study. AB - Ankle ulcers associated with venous disease have been traditionally treated by Unna's compressive bandages. However, successful healing of an ulcer with this therapeutic modality is slow and tedious. The purpose of this study is to investigate whether adjunctive sclerotherapy of large venous channels near the ulcers enhances healing. Twenty-eight patients with perimalleolar venous ulceration were entered into this study. Ulcer size ranged from 6.0 to 25 cm2. All were examined for the presence of large venous channels adjacent to the ulcer bed. A portable continuous-wave Doppler supplemented digital examination of the area. Twenty-five out of 28 patients had easily detectable venous channels, and these were randomized into two groups: group I, treated by weekly changes of Unna's compressive boots; group II, treated by weekly change of Unna's compressive boots and sclerotherapy with 3% sodium tetradecyl sulfate (Sotradecol). All patients had the size of the ulcer measured during their weekly visits. Patients in group II took a mean of 2.1 weeks to exhibit 50% healing and 4.3 weeks to fully heal. Conversely patients in group I took a mean of 3.2 weeks to achieve 50% healing and 6.1 weeks to fully heal. Thus, healing was significantly faster (p less than 0.05) in group II. In conclusion, the therapeutic efficiency of Unna's compressive bandaging is significantly enhanced by the adjunctive sclerotherapy of adjacent venous channels. PMID- 2325218 TI - Graft angioplasty: use of the stenotic lesion as an inflow or outflow site in lower extremity arterial bypasses. PMID- 2325219 TI - Growth factor gene expression by intimal cells in healing polytetrafluoroethylene grafts. AB - Vascular smooth muscle cell proliferation resulting in intimal hyperplasia is a major cause of late graft failure. In baboons, healing 60 microns internodal distance polytetrafluoroethylene vascular grafts form an intima composed of proliferating smooth muscle cells with a luminal lining of endothelium. The presence of intimal smooth muscle cell proliferation underneath an intact endothelium, without platelet adherence, suggests that intimal cells rather than platelets may provide the growth factors regulating the smooth muscle cell proliferation. This idea is supported by the observation that, when segments of graft and artery are excised and perfused ex vivo, there is greater mitogenic activity present in the graft perfusate compared to artery perfusate. Two factors expressed by vascular wall cells and known to influence smooth muscle cell growth in vitro are platelet-derived growth factor and transforming growth factor-beta 1. The expression of these growth factors was measured by Northern blot analysis of total ribonucleic acid extracted from thoracic aorta and the intima of 6-week thoracoabdominal polytetrafluoroethylene grafts, and from smooth muscle cell cultured from the aorta and polytetrafluoroethylene graft. Growth of the cultured smooth muscle cell was arrested in serum-free conditions for 3 days and then stimulated with 10% fetal calf serum. Twenty-four hours later, the smooth muscle cells were harvested. Probing the blots for platelet-derived growth factor-A, platelet-derived growth factor-B, and transforming growth factor-beta 1 messenger ribonucleic acid revealed that in vivo, the graft intima expressed more platelet derived growth factor-A than the aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325220 TI - Occult antithrombin III deficiency: a potentially lethal complication of the postphlebitic limb. AB - Chronic venous insufficiency is a frequent sequel to lower extremity venous thrombosis. A relatively uncommon, but potentially lethal, cause of the thrombosis is congenital antithrombin III deficiency. Recognition and treatment of this occult deficiency is critical. The following report describes a family treated by the authors for this problem. In one generation of nine siblings, three males had documentation of the disease with functional antithrombin III levels in the range of 50% to 60%. Before evaluation for the deficiency one female sibling died at the age of 20 years as a consequence of a proven pulmonary embolus. Antithrombin III levels in another female sibling, who was free of symptoms, were normal (80% to 120%). Four other siblings who were free of symptoms (one female, three males) refused evaluation. All three men with the deficiency had severe, chronic, bilateral, lower extremity, venous insufficiency manifested by pain, varicosities, edema, pigmentation, and ulceration. Despite chronic warfarin therapy, one experienced recurrent pulmonary embolization with eventual loss of perfusion of the entire right lung. Ascending venography in the symptomatic males with the deficiency revealed evidence of recurrent and diffuse venous thrombosis with partial recanalization. Recurrent lower extremity venous thrombosis consequent to antithrombin III deficiency causes a particularly fulminant postphlebitic syndrome with characteristic venographic findings. Although potentially lethal if unrecognized and treated simply as venous insufficiency, chronic therapy with warfarin offers palliation and prolongs life. PMID- 2325221 TI - Efficacy of corticosteroids in suppression of intimal hyperplasia: a possible antiangiogenic effect. PMID- 2325222 TI - From the Centers for Disease Control. International Task Force for Disease Eradication. PMID- 2325223 TI - High hopes--and many morals. PMID- 2325224 TI - DNR and autopsy: a linked Bayesian system. PMID- 2325226 TI - The detection of depression and the financing of medical care. PMID- 2325225 TI - Women and specialties. PMID- 2325227 TI - Metoclopramide and exercise-induced nausea. PMID- 2325228 TI - Preoperative banditry: surgeons react. PMID- 2325229 TI - Cyanoacrylate nail glue mistaken for eye drops. PMID- 2325230 TI - Return to low-altitude sickness: an entity that doesn't exist. PMID- 2325231 TI - Systeme international units and familiar formulas: the case of lipids. PMID- 2325232 TI - Acute HIV infection presenting with painful swallowing and esophageal ulcers. AB - We describe an acute human immunodeficiency virus (HIV) infection in 16 homosexual men who presented with painful swallowing (odynophagia). Eleven men had a maculopapular rash and 3 had palatal ulcers. At esophagogastroduodenoscopy (endoscopy), multiple discrete esophageal ulcers measuring 0.3 to 1.5 cm in diameter were observed. Electron microscopy of biopsy specimens taken from the ulcer margins in 8 men revealed viral particles 120 to 160 nm in diameter whose morphologic characteristics were those of retroviruses. Human immunodeficiency virus seroconversion was documented in 15 men by Western blot analysis. In 3 men, HIV-1 was isolated from peripheral blood mononuclear cells, in 2 men HIV-1 was isolated from peripheral blood monocytes, and in 1 man HIV-1 was isolated from tissue taken from the margins of the esophageal ulcers. These observations extend our knowledge of the clinical spectrum of acute HIV infection syndromes and suggest that cells in the esophagus are a target for HIV-1 infection. PMID- 2325233 TI - Seasonal trends in US asthma hospitalizations and mortality. AB - Asthma morbidity is known to exhibit seasonal periodicity. Yet the relationship between trends in morbidity vs mortality is not known. This report describes and compares the seasonal variation in asthma hospitalizations and mortality in the US population. During 1982 through 1986, both mortality and hospitalizations demonstrated periodic seasonal trends that were age specific and did not differ by sex, race, or region. For persons aged 5 through 34 years, hospitalizations peaked in September through November, whereas mortality trends peaked in June through August. A disproportionate number of the summer deaths in this age group occurred out of the hospital. For individuals 65 years old or older, both asthma hospitalizations and mortality demonstrated increases during December through February. The results of this study demonstrate age-specific seasonal variations in the clinical expression of asthma. Perhaps the treatment and prevention of asthma hospitalizations and mortality might be improved through further understanding of these trends. PMID- 2325234 TI - Medication prescribing errors in a teaching hospital. AB - A study of prescribing errors committed by physicians that occurred in a tertiary care teaching hospital is reported. From a total of 289 411 medication orders written during the 1-year study period, 905 prescribing errors were detected and averted, of which 522 (57.7%) were rated as having potential for adverse consequences. The overall detected error rate was 3.13 errors for each 1000 orders written and a rate of 1.81 significant errors per 1000 orders. The error rate (4.01 per 1000 orders) was greatest between 12 pm and 3:59 pm. First-year postgraduate residents were found to have a higher error rate (4.25 per 1000 orders) than other prescriber classes, and obstetrics/gynecology services (3.54 per 1000 orders) and surgery/anesthesia services (3.42 per 1000 orders) had greater error rates than other services. The study results demonstrate the significant risk to patients from medication prescribing errors. Educational, operational, and risk-management activities should include efforts directed at reducing the risk to patients from prescribing errors. PMID- 2325235 TI - A piece of my mind. HOPE. PMID- 2325236 TI - From the Office of the General Counsel. Advance medical directives. PMID- 2325237 TI - Effect of commercially available chemically defined liquid diets on the intestinal microflora and bacterial translocation from the gut. AB - The effect of chemically defined liquid diets on the intestinal microflora and bacterial translocation from the gut was studied in the rat. Seventy-five female Fischer rats were randomized to five groups of 15 animals each. Group I was fed rat chow and water, group II was fed Vivonex TEN, group III was fed Ensure, group IV was fed Enrich, and group V was fed Ensure plus ground corn cobs, a crude fiber source. Animals were fed their respective diets ad libitum for 1 week and then killed. Quantitative culture of the mesenteric lymph nodes (MLN) and cecum was performed to determine bacterial translocation from the gut. A 66% translocation rate (10/15) of bacteria to MLN was observed in the animals fed Ensure and Enrich compared to 21% in the Vivonex TEN group (3/14) and 20% in the animals fed Ensure plus ground corn cobs (3/15). None of the animals in the control group eating their normal diets of rat chow and water developed positive MLN. Statistical significance (p less than 0.001) was achieved between the Ensure and Enrich groups when compared to controls but not between the Vivonex TEN and Ensure plus corn cobs. Cecal culture revealed a statistically significant rise in cecal bacteria in all groups when compared to the control group (group I). These results indicate that chemically defined liquid diets result in altered intestinal microflora and bacterial translocation from the gut. PMID- 2325238 TI - Tissue accumulation of Al in twins. PMID- 2325239 TI - Repositioning the wayward central venous catheter. PMID- 2325240 TI - Early spontaneous retraction of indwelling catheters of totally implantable venous access devices. PMID- 2325241 TI - Pharmacological concentrations of lipid emulsions inhibit interleukin-2-dependent lymphocyte responses in vitro. AB - Most immunological functions are accomplished by means of interactions between mediator molecules (cytokines or lymphokines) and their specific receptors on the lymphocyte surface. One particular lymphokine, Interleukin-2 (IL-2) is central to the generation of most immune responses including those with antitumor activity. Prompted by two clinical trials which have suggested distinct but apparently opposite effects of lipid emulsions on the production of and lymphocyte responses to IL-2 we have examined the effects of pharmacological concentrations of three lipid emulsions currently in clinical use on IL-2 related interactions in vitro. Mitogen-stimulated and IL-2 activated human lymphocyte proliferation were both inhibited in a dose-dependent manner in the presence of all three lipid emulsions although the effects were less marked with the solution in which 50% of the calories are present as medium-chain triglycerides (MCT) rather than long-chain triglycerides (LCT). Similarly the LCT, but less so the MCT-containing solutions inhibited the generation of cytotoxic lymphokine-activated killer cells. These solutions did not inhibit the proliferation of cell lines which are not growth factor dependent but did inhibit the growth of an IL-2-dependent cell line. We conclude that lipid emulsions can upset IL-2-dependent lymphocyte responses. These observations may lead to parenteral feeding regimens which are less immunocompromising for the tumor-bearing patient. PMID- 2325242 TI - Dietary nucleotide effects upon murine natural killer cell activity and macrophage activation. AB - Weanling mice fed chow or chow plus water supplemented with 3.5 mg of nucleotides per 100 ml of water for 6 weeks exhibited increased natural killer cell (NK) activity and lower macrophage activation compared to mice fed chow plus nonsupplemented water. In a dose-response study, NK activity, macrophage activation and spleen weight (as a percentage of body weight) were higher in mice fed up to 0.035% w/w nucleotides, however macrophage activation was decreased by feeding over 0.35% w/w compared to those receiving basal purified diet (BPD). Nucleotides in human milk may affect the immune response in breast-fed infants. PMID- 2325243 TI - A prospective study of complications in Hickman right-atrial catheters in marrow transplant patients. AB - One hundred forty-three large bore right-atrial catheters (RACs) in 111 bone marrow transplant recipients were prospectively analyzed for the incidence of complications interfering with catheter function. Of the 143 RACs, 108 (76%) were patent on departure from Seattle or death. Infectious complications occurred in 63 (44%) of the catheters, resulting in 18 (13%) removals. Noninfectious complications occurred with 54 (38%) of the catheters, resulting in 17 (12%) removals. Successful interventions included catheter repair, dissolving precipitates with ammonium chloride solution, and declotting catheter lumens with heparin and/or urokinase. We conclude that RACs continue to be reliable and safe devices to use in marrow transplant patients. Complications interfering with catheter function are frequent; however, most can be resolved without the need to remove the catheter. PMID- 2325244 TI - Metabolic rate and weight loss in chronic obstructive lung disease. AB - Although weight loss is a common problem in chronic obstructive pulmonary disease (COPD), the precise cause of malnutrition in COPD patients is not known. The purpose of this study was to measure and compare resting energy expenditure (REE) in stable undernourished and adequately nourished COPD. REE was measured in normal, adequately nourished, and undernourished COPD patients by indirect calorimetry and then compared to predicted basal metabolic rate (BMR) calculated from the Harris-Benedict equation. We found that measured REE, compared to predicted, was significantly higher in the undernourished group, (1.15 +/- 0.02) and compared to the adequately nourished COPD (0.99 +/- 0.03) and normal groups (0.93 +/- 0.02) (p less than 0.0001). We conclude that there is a hypermetabolic state in stable malnourished COPD patients which may be a factor in weight loss. This elevated REE also needs to be taken into account when determining caloric requirements for COPD patients. PMID- 2325245 TI - Blood and tissue tocopherol levels in rats following intraperitoneally administered alpha-tocopheryl acetate. AB - The correction or maintenance of blood and tissue alpha-tocopherol (alpha-Toc) levels by intraperitoneally administered all-rac-alpha-tocopheryl acetate (alpha Tac) was compared with RRR- alpha-tocopherol (alpha-Toc) in vitamin E-depleted and control rats. Rats received 1.3 TE vitamin E daily for 7 days. alpha-Tac was detected in plasma of one-third of alpha-Tac-treated rats 24 hr after the first treatment, although not in subsequent samplings. Both alpha-Tac and alpha-Toc increased tocopherol levels in plasma and liver of E-deprived rats, while little or no change was observed in adipose tissue and brain. Similarly, control rats treated with alpha-Tac or alpha-Toc had significantly greater (p less than 0.05) plasma and liver alpha-Toc levels at day 3 and day 7 than did saline-treated rats. There was no significant difference in adipose alpha-Toc levels among treatment groups of control rats. The results of this study suggest that alpha Tac is rapidly hydrolyzed to its biologically active alcohol form and results in similar effects to that of intraperitoneally administered alpha-Toc. PMID- 2325247 TI - [Problems of the emergency care system]. PMID- 2325246 TI - Serum iron, zinc, copper, selenium, and bromide concentrations after coronary bypass operation. AB - The effect of surgical trauma on serum trace elements was studied in 10 patients undergoing coronary bypass surgery. After the initial decrease due to the hemodilution during operation serum iron, zinc, copper and selenium remained depressed for the immediate postoperative period. Zinc was still at significantly lower level 2 months after the operation. Low serum iron values were also observed. Changes in trace element concentrations were parallel with changes in the concentrations of their transport and binding proteins in the serum. The multielemental technique also measured nonessential bromide, which returned to initial levels in 7 days. Effects of trauma on metabolism, acute phase reaction with redistribution of zinc and copper and losses via increased urinary excretion explain the above changes. Development of a subclinical deficiency of zinc and possibly iron is suggested by the persistence of low serum levels during recovery after operation. PMID- 2325248 TI - [Effects of controlled hypotension induced by prostaglandin E1 on the cerebral blood flow]. AB - The effect of controlled hypotension induced by prostaglandin E1 (PGE1) on the cerebral blood flow (CBF) was studied in 14 patients undergoing neurosurgery. CBF was measured by thermal diffusion using a flow probe with a Peltier stack. PGE1 was injected i.v. continuously, at a dose of 0.05, 0.1 and 0.2 micrograms.kg 1.min-1. CBF tended to increase dose-dependently but not significantly by PGE1 administration. Cerebral vascular resistance was reduced significantly by every dose of PGE1 administered. Therefore, the results indicate that the cerebral vascular beds are dilated directly by PGE1. In conclusion, this study suggests that PGE1 can be used safely to control hypotension without reducing CBF during neurosurgery. PMID- 2325249 TI - [Studies on ECMO. (III)--Study on pumpless A-V ECMO]. AB - Silicon hollow fiber membrane oxygenator is considered to be useful for long term extracorporeal membrane oxygenation (ECMO) and blood usually flows inside of the fiber (inside flow type). But if it flows outside of the fiber (outside flow type), the pressure drop is supposed to be less than that of inside flow type. In this study the oxygenator of an outside flow type was used. At first, the pilot study was done to evaluate the capability of this oxygenator as an outside flow type. The pressure drop was 50 mmHg at the blood flow of 400 ml.min-1. At this blood flow and same gas flow, CO2 transfer rate was 22.3 ml.min-1. In the second study, the effects of pumpless arterio-venous ECMO (pumpless A-V ECMO) were studied in 8 dogs under mechanical hypoventilation. During ECMO, there were no significant changes in hemodynamics when the blood flow rate was 15% of cardiac output. PaO2 and PaCO2 recovered considerably. In conclusion, pumpless A-V ECMO using this membrane oxygenator of outside flow type is effective for CO2 removal and considered to be clinically useful. PMID- 2325250 TI - [Effect of cimetidine on neuromuscular blockade by succinylcholine and pancuronium]. AB - The effect of cimetidine on neuromuscular blockade by succinylcholine and pancuronium was investigated in 54 adult patients scheduled for elective surgery. The neuromuscular blocking properties were estimated with single twitch height (T1) which was obtained by measuring the acceleration of adduction of the thumb in response to the ulnar nerve stimulation under N2O-fentanyl anesthesia. In cimetidine group, cimetidine 200 mg was administered orally on the night before surgery and 90 mins before anesthesia. Succinylcholine 1 mg.kg-1 (n = 14) or 1.5 mg.kg-1 (n = 20) was injected intravenously, and the onset time (from injection to 0% T1), the duration of maximal block (0% T1), and the recovery time from injection to 50% and 75% of control twitch height were evaluated. ED25 and ED50 of pancuronium were calculated from the dose response curve obtained by incremental administration of the drug (n = 20) whose total cumulative dose was 0.1 mg.kg-1. The recovery index of pancuronium was determined by measuring the 25%-75% recovery time. There was no significant difference between cimetidine pretreated patients and non-pretreated patients regarding these parameters of neuromuscular blockade with both succinylcholine and pancuronium. In conclusion, cimetidine has no influence on neuromuscular blockade of succinylcholine and pancuronium under N2O-fentanyl anesthesia. PMID- 2325251 TI - [The effects of epinephrine added to epidural morphine]. AB - The authors studied the influence of epinephrine added to epidural morphine on morphine pharmacokinetics. Epidural morphine 3mg in 10ml of saline solution was administered from the Th11-12 interspace to 14 patients undergoing right thoracotomy. In addition, epinephrine 50micrograms was added to the epidural solution in 8 patients selected randomly. Morphine concentrations in the azygos vein and radial artery samples were measured. Compared with the plain morphine group, addition of epinephrine significantly decreased morphine concentrations in the azygos vein only at 5 and 10min after administration. At 15 and 30min after administration, the azygos vein morphine concentrations in the epinephrine group were at the same level as in the plain morphine group. The admixture of epinephrine with epidural morphine increased the individual variation in the half life of morphine concentrations in the azygos vein. All these results suggest that addition of epinephrine does not play a particularly important role in causing prolonged and profound analgesia after epidural morphine. PMID- 2325252 TI - [Effects of lidocaine and its metabolite, monoethylglycine xylidide (MEGX), on transmembrane action potentials in guinea-pig papillary muscles]. AB - Effects of lidocaine 5, 10, 20 micrograms.ml-1 and its metabolite, MEGX 5, 10, 20 micrograms.ml-1, on transmembrane action potentials were studied in isolated guinea-pig papillary muscles, perfused with modified Tyrode's solution. The basic driving rate was 1 Hz and the rate was changed from 1 Hz to 0.25, 0.5, 2, 3 and 4 Hz in a stepwise manner. Both lidocaine and MEGX produced dose- and rate dependent depression of maximum rate of rise of action potential (Vmax) without significant changes in resting membrane potentials. The recovery kinetics of Vmax was studied by either applying premature stimuli at basic driving rate of 0.25 Hz or by stopping the basic driving of 1 Hz for 1s to 60s. A slow component (time constant: 176-206 ms for lidocaine, 300-340 ms for MEGX) was observed in premature response. And a slower component (time constant: 3-4s for MEGX) was observed in the first response after stopping stimulation. Both drugs shortened the action potential duration. These results suggest that MEGX has a lidocaine like class I antiarrhythmic actions and that it might modify the actions of lidocaine especially in patients with elevated plasma MEGX concentration. PMID- 2325254 TI - [Effects of sevoflurane anesthesia and baroreceptor function on renal sympathetic nerve activity in rats]. AB - Effects of sevoflurane at various anesthetic levels on renal sympathetic nerve activity (RSNA), blood pressure and heart rate were studied in rats. Changes of these parameters produced reflexly by noxious cutaneous stimulation and effects of baroreceptor on them were also studied. Under the resting condition by increasing inspired sevoflurane concentration decreased blood pressure and heart rate dose-dependently, whereas, RSNA was unchanged. But, without the baroreceptor function, RSNA decreased and the change paralleled with changes of blood pressure and heart rate. When noxious stimulation was applied on a hindpaw by pinching, blood pressure, heart rate and RSNA all increased at sevoflurane 2.1%. The responses of these parameters were attenuated at 3.1% and almost disappeared at 4.2% of sevoflurane. However, without the baroreceptor function, RSNA increased even at 3.2 and 4.2% as at 2.1% of sevoflurane. It is suggested that under sevoflurane anesthesia, baroreceptor system has strong influences on RSNA even under sevoflurane 4.2% (2MAC). PMID- 2325253 TI - [Protective effect of calcium channel blockers on the liver against halothane hepatitis in rats]. AB - This study examined whether nifedipine or flunarizine, calcium channel blockers, could protect the liver against halothane hepatotoxicity in rats. Six groups of 102 enzyme-induced male Sprague-Dawley rats were studied. Group N1 and N2 rats received nifedipine 20 micrograms and 100 micrograms.kg-1.day-1, and group F1 and F2 rats received flunarizine 100 micrograms and 1mg.kg-1.day-1 in their drinking water for 24 hours prior to the experiment. They were then anesthetized with N2 O2-halothane 0.5% under the condition of hypoxia (FIO2 0.12) for two hours. Animals in group H were given clear water, and then anesthetized with halothane and hypoxia. Animals in group C were given clear water and exposed to hypoxia alone. Twenty-four hours after anesthesia, all animals were decapitated and their liver specimens were stained with H&E for the examination by light microscopy. Eighty percent of rats in group H showed centrilobular degeneration, but administration of nifedipine or flunarizine reduced the incidence significantly. Furthermore, histological score graded from 0 to 3, according to the degree of centrilobular degeneration was also significantly reduced by administration of nifedipine or flunarizine. These results suggest that oral administration of nifedipine or flunarizine could prevent the incidence of halothane-induced hepatotoxicity in enzyme-induced rats, probably by preventing the increase in cytosolic calcium concentration. PMID- 2325255 TI - [Clinical study of propofol in male volunteers]. AB - A clinical phase 1 study of intravenous anesthetic, propofol, was carried out in 6 male volunteers. Propofol, 1, 2, and 2.5 mg.kg-1, was administered intravenously. Anesthetic effects and effects on vital signs, such as blood pressure, heart rate, respiratory rate and body temperature, were investigated. Any adverse effects or abnormal laboratory findings were also investigated. Venous blood samples were obtained frequently for 12 hours to measure blood propofol concentrations. One volunteer out of 6 lost consciousness with 1 mg.kg-1 and the remaining with 2 mg.kg-1 within 1.5 min. In 2 volunteers the duration of anesthesia was inadequate for clinical practice with 2 mg.kg-1. Therefore, 2.5 mg.kg-1 was given. Rhythmic high voltage slow waves appeared immediately after the loss of consciousness in EEG and then basic activity changed to 11 approximately 16 Hz, 30 approximately 60 microV. Blood pressure decreased and heart rate increased but no profound hypotension was observed. Body temperature decreased. No adverse effect, such as laryngospasm, bronchospasm or hiccough, occurred. Laboratory test showed no abnormal result. Pharmacokinetic analysis was carried out using a 3 compartment open model. The half time of distribution phase, 2.6 min, was short, and total clearance, 1.68 l.min-1, was high. We conclude that the proper induction dose of this agent is 2 approximately 2.5 mg.kg-1, which is similar to the values previously reported in European investigations, and that this agent is safe and useful for induction of anesthesia. PMID- 2325256 TI - [Midazolam for rapid sequence induction]. AB - We compared midazolam 0.2 mg.kg-1 and fentanyl 50 micrograms with thiamylal 4 mg.kg-1 for rapid sequence induction. We could use midazolam safely in patients with bronchial asthma or drug allergy. There was no difference in time from the beginning of induction to intubation between midazolam treated group and thiamylal treated group. Changes in systolic as well as diastolic blood pressure and heart rate during 2 hours from intubation were smaller in midazolam treated group than in thiamylal treated group. In midazolam treated group, no arrhythmias were observed at the time of intubation. We could reduce the amount of anesthetics in midazolam treated group during 2 hours from intubation. From the results mentioned above, we conclude that midazolam is a useful agent for rapid sequence induction. PMID- 2325257 TI - [Continuous epidural infusion of bupivacaine and morphine for postoperative pain relief]. AB - Forty-five patients admitted to the intensive care unit following thoracic or abdominal surgery received continuous epidural infusion of bupivacaine and morphine for 48 hours. During the first 10 hours, the patients received 0.25% bupivacaine solution with 0.005% morphine at the rate of 4 ml.h-1, and bupivacaine concentration was decreased to 0.125% with the same morphine concentration. The mean infusion rate of bupivacaine during 48 hours was 0.12 +/- 0.03 (SD) mg.kg-1.h-1 and that of morphine was 4.0 +/- 1.0 micrograms.kg-1.h-1. Thirty-one patients (69%) complained no pain on deep breathing at 24 hours and 33 patients (74%) required no other type of analgesics during this study. The mean plasma bupivacaine concentration was 0.6 +/- 0.3 microgram.ml-1 at 48 hours. Hypotension defined as systolic arterial pressure below 90 mmHg and itching were observed in 15 patients (33%), but no other severe side effects were noted. Continuous epidural infusion of bupivacaine and morphine mixture for 48 hours postoperatively provided effective pain relief with a low incidence of side effects. PMID- 2325258 TI - [Selective percutaneous thermocoagulation of the glossopharyngeal nerve in intractable glossopharyngeal neuralgia]. AB - Percutaneous radiofrequency thermocoagulation of glossopharyngeal nerve at the jugular foramen was employed for the treatment of intractable glossopharyngeal neuralgia in three cases, one with essential and two with symptomatic pain from malignant tumor of the oropharyngeal area. Under radiological control, the thermocoagulation electrode was inserted through the lateral cervical route, and the electrode reached the jugular foramen with the tip toward the pars nervosa. The correct position of the electrode was confirmed by radiography and by electrophysiological stimulation test. Once the electrode was properly positioned, lesion was made with temperature of 60 degrees C to 70 degrees C for 1 approximately 2 minutes. Surgical results were satisfactory and no neurological and cardiovascular complications were noted. Percutaneous radiofrequency thermocoagulation of glossopharyngeal nerve is thought to be very useful for the treatment of intractable glossopharyngeal neuralgia. PMID- 2325259 TI - [A case of herpes zoster ophthalmicus with complete ophthalmoplegia]. AB - A 58-year old man with herpes zoster ophthalmicus developed complete ophthalmoplegia, dissemination of herpetic lesions and meningitis. Eye movements improved two month after the onset of zoster. Five months later, eye movements recovered completely, but his sight was disturbed severely due to corneal ulcer. PMID- 2325260 TI - [Sudden cardiac arrest during percutaneous nephrostolithotomy (PNL) under epidural anesthesia]. AB - There have been few major complications of percutaneous nephrostolithotomy (PNL) reported. We recently experienced cardiac arrest during PNL under epidural anesthesia. The patient was a 52 year old man weighing 64 kg who had been suffering from right renal pelvic stone for years. He was scheduled for PLN under epidural anesthesia. Analgesia was obtained to the level of Th6. The operation proceeded uneventfully for about 60 min. By this time, he suddenly complained nausea, and hypotension with bradycardia occurred. Blood pressure and pulse rate returned immediately to the normal level by IV atropine and ephedrine. But after three minutes, blood pressure and pulse rate went down again. This hypotension with bradycardia was unresponsive to epinephrine, calcium chloride and sodium bicarbonate. This was followed by asystole. Resuscitation was successful with the addition of epinephrine, calcium chloride, and sodium bicarbonate about 15 min after cardiac massage had started. The patient was, on the fifth postoperative day, with no evidence of impairment of renal, cardiac and respiratory functions but a slight impairment of neurologic function. Several possible causes for this cardiac arrest and anesthetic management of percutaneous nephrostolithotomy are discussed. PMID- 2325262 TI - [63d symposia of the Japan Society of Bacteriology. Tokushima, 27-29 March 1990. Abstracts]. PMID- 2325261 TI - [Veno-arterial ECLA (extracorporeal lung assist) for severe respiratory failure due to meconium aspiration]. AB - A full term newborn female, 3262g, aspirated meconium at birth and began to suffer from severe hypoxia and acidosis due to progressing pneumonitis, pneumothorax and pneumomediastinum. She also had severe hypotension and anuria. Venoarterial ECLA with a Kolobow membrane lung via the right internal jugular vein and the right common carotid artery was initiated. Blood gas parameters and blood pressure improved, and urine output increased to normal. ECLA permitted a reduction in FIO2 and airway pressure of mechanical ventilation, as well as frequent lavage of the lung. As the physical condition improved, the bypass flow was gradually decreased from 200 ml.kg-1.min-1 at the start to 130 ml.kg-1.min-1 for maintenance, then to 25 ml.kg-1.min-1 at the end. Bleeding throughout the ECLA for 69 hours could be minimized by a meticulous control of the activated coagulation time with a minimum dose of heparin and the transfusion of fresh frozen and platelet rich plasma. After ECLA, the carotid artery was simply ligated, and mechanical ventilatory support was carried out for 5 days. Her condition improved and she left the hospital without any neurological sequelae. ECLA will become an effective means of life support for a baby with severe MAS irresponsive to conventional ventilatory support. PMID- 2325263 TI - [Flow cytometric DNA analysis of papillary carcinoma of the thyroid using paraffin-embedded specimens]. AB - A flow cytometric DNA analysis of papillary thyroid carcinomas has been performed on paraffin-embedded specimens, in order to determine the clinical usefulness of this method by defining the degree of the biological malignancy. Fifty-eight patients with papillary carcinomas were followed from 2 to 8 years. They were classified according to their prognosis into three groups: non-recurrent (47 patients), recurrent (5 patients), and a deceased group (6 patients). Aneuploidy was found in 6 (10.3%) of the total 58 patients. It was more frequently detected in the recurrent (40%) and in the deceased (33.3%) groups than in the non recurrent group (4.3%). Higher proliferating index values were observed in the deceased group than in the recurrent and non-recurrent groups. These results indicate that a DNA analysis, using routine paraffin-embedded materials, is a useful adjunct in the determination of the degree of the biological malignancy of a papillary carcinoma. PMID- 2325264 TI - [A clinico-pathological study of the intraepithelial spreading of esophageal carcinomas]. AB - One hundred and twenty-nine esophageal epidermoid carcinomas have been found to have 60 intraepithelial-spreading lesions. According to the histological of these intraepithelial-spreading lesions, 60 of these lesions could be divided to two types: a whole type and a basal type. Thirty-three lesions (55%) were found to be a whole type and twenty-three lesions (38%) a basal type, and the remaining four lesions (7%) a mixed type. Sixty-seven percent of the whole type lesions were accompanied by well differentiated epidermoid carcinomas, and 33% with poorly or moderately differentiated epidermoid carcinomas. On the other hand, 17% of the basal type lesions were accompanied by well differentiated epidermoid carcinomas, and 83% with a poorly or moderately differentiated epidermoid carcinomas. The average length of spreading of the whole type was 14.5 mm, and the average length of spreading of the basal type, 19.6 mm. It was found that the intraepithelial spreading of the poorly differentiated epidermoid carcinomas (average: 23.6 mm) was longer than the well differentiated epidermoid carcinomas (average: 15.8 mm). A histological examination of step sections revealed that 34% of the intra spreading lesions had erosions. Further half of the lesions over 10 mm in length also had erosions. Basal type carcinomas had a greater frequency of erosion than did the whole type carcinomas. Papillary growth pattern was a special histological feature of the whole type, and a pagetoid spreading was distinctive in the basal type. The macroscopical appearance of the mucosal surface of the whole type was granular or nodular, whereas for the basal type it was redness or no change. PMID- 2325265 TI - [A case-control study of the etiologic factors of a multiple primary cancer following a prior first breast cancer]. AB - At the Kanagawa Cancer Center, the cases of 48 women who were found to have a multiple primary cancer (MPC) and who had previously had a first breast cancer (FBC) were reviewed, and a hospital-based, matched-pair, case-control study was performed. Studied were the effects of the reproductive factors, the therapies for their FBC, their drinking and smoking habits, and similar criteria on the development of the MPC. The case-control pairs were matched for age, year of their FBC diagnosis, and place of residence. The controls had only breast cancer and each lived beyond the MPC patient with whom they had been matched. The odds ratios for radiation therapy and drinking habits, calculated by McNemar's Test, were 4.00 (95% CI = 1.06-17.82) and 8.00 (1.03-170.60), respectively. PMID- 2325266 TI - [In vitro induction of cytotoxic activity against carcinomatous pleural or peritoneal lymphoid cells cultivated with cytokines, and an immunological phenotypic analysis of the effector cells]. AB - The functional and phenotypic characteristics of carcinomatous pleural or peritoneal lymphoid cells cultivated with either rIL 2 or TCGF have been investigated. The cultivation of the lymphoid cells with cytokines was initiated by a mixture of coexisting, viable carcinoma cells for 14 days. Results have indicated that cytokine-activated lymphoid cells from malignant pleural and peritoneal effusions showed considerable cytolytic activity against K562 and Daudi cells. The cell population responsible for LAK and/or CTL effector cells of TCGF-activated lymphoid cells were CD8+ CD11- cells. Further, in rIL 2-expanded cultures from pleural and peritoneal lymphoid cells, the CD4+ Leu 8- population was found to contain effector cells of cytotoxic activity against the tumor cells. It further was seen that the TCGF-activated CD8+ CD11- T cells possessed a more potent killing activity, in comparison to the rIL 2-activated CD4+ Leu8- T cells. However, rIL 2-activated lymphoid cells from ascites in liver cirrhosis (used for a control) showed a higher tumoricidal activity. PMID- 2325267 TI - [Pathological studies of multiple submucosal gastric gland lesions in thirty eight cases]. AB - We have examined 38 stomachs with the adenocarcinoma and multiple submucosal gastric gland (SG) lesions. Almost the SG lesions consisted of the foveolar epithelium, which stained negative with alcian blue whereas the ordinary glands stained positive with con-A (III), or with both types of epithelium, and they had no atypicality. Only 14 out of 2,188 SG lesions (0.63%) showed atypical proliferation. Three hundred and forty-nine out of 1,535 SG that were examined by lysozyme staining were strongly lysozyme positive. Almost all the propria mucosa in the areas of the minute SG showed erosive lesions with an atrophy of ordinary glands, glandular erosion, and a regenerative epithelium. Eleven stomachs (11/38 cases, 29.0%) had multiple adenocarcinomas. PMID- 2325268 TI - [A case of malignant mesenchymoma of the maxilla]. AB - The case of a 48-year-old male with a malignant mesenchymoma of the maxilla is reported. The patient had complained of bloody rhinorrhea and cheek pain, and a total maxillectomy was performed. The tumor consisted of a rhabdomyosarcoma, an osteosarcoma and a chondrosarcoma, which were relatively differentiated. Later, recurrence of a tumor and a lung metastasis occurred, however the tumor revealed undifferentiated mesenchymal cells. This led us to suspect the origin of the malignant mesenchymoma had been a primitive mesenchymal cell. To our a knowledge, the present case is the first reported case of a malignant mesenchymoma with a maxillary origin in the world. PMID- 2325269 TI - [Brachytherapy of choroidal melanoma using radioactive gold grains--a case report]. AB - A brachytherapy of a choroidal melanoma using 198Au grains has been performed. Procedurally, the sclera was first incised, after which a pouch was constructed and the grains then arranged around the tumor in a circle so as to enclose it, said operative procedure according to the Manchester Technique. Total Gy dosage amounted to 120 Gy. Postoperatively, in due course, the disappearance of the tumor was clearly shown on MRI examination. The small size and the short half life of the gold grains made it possible to insert the grains into the tissue permanently, and to give an adequate Gy dosage to eradicate the tumor while still preserving the eyeball. PMID- 2325270 TI - [A serous cystadenoma of the ovary of borderline malignancy with a fifteen-year history. A case report]. AB - A case of a serous cystadenoma of a ovary of borderline malignancy is reported. Sixteen years earlier, the patient had undergone an exploratory laparotomy because of ovarian tumor, and the histologic diagnosis had been a serous cystadenocarcinoma. Postoperative chemotherapy was not effective and drainage of the tumor fluid had been performed for 15 years, with the estimated drainage volume estimated to have reached, 1,000 1. Gradual malnutrition and marked tumor growth then become apparent. A reevaluation of the initial histologic slides and her clinical course strongly suggested a serous cystadenoma of borderline malignancy. Thus a tumor resection, a bilateral salpingo-oophorectomy, and a hysterectomy was performed. A histologic diagnosis of a resected specimen confirmed a serous cystadenoma of borderline malignancy and the histologic features were quite similar to those of the initial biopsy specimens. The patient is living well postoperatively for 8 months without postoperative chemotherapy. PMID- 2325271 TI - [MR imaging for lung cancer in evaluating local invasion; referring to CT and surgical-histological basis]. AB - The diagnostic potentiality of MR imaging for lung cancer was researched in 17 patients in evaluating local invasions based on surgical-histological evidence. Comparative reviewing with CT was also performed. MR imaging appeared to have an ability unique to portray malignant invasions somewhere such as in the hili or apices. On the other hand, there were also some diagnostic limitations of MR imaging in delineating the localized invasive changes. On the way of working up lung cancer, CT still may stand at the first choice as a radiographic staging procedure which provides the more detailed anatomic-pathologic informations. We consider that MR imaging is mandatory when CT and/or other modalities could'not obtain efficient results. PMID- 2325272 TI - [MRI of an intrathoracic malignant tumor invading the chest wall]. AB - 22 patients with intrathoracic malignant tumors suspected of invading the chest wall were examined with CT and MRI. Chest wall invasion was operatively confirmed in 19 cases and excluded in the other 3 cases. CT showed tumor infiltration of the chest wall in 14/19 cases, no morphological changes in 5/19 cases. Thoracic wall invasion was demonstrated by MR in all 19 cases. Typical MR finding of malignant invasion was local lesion within the chest wall showing high signal intensity in post-Gd T1-weighted images and in T2-weighted images. Reactive inflammatory changes as well as malignant infiltration of the pleura showed high signal intensity on enhanced T1-weighted images and on T2-weighted images. PMID- 2325273 TI - [Evaluation of MRI for the staging of esophageal cancer]. AB - The usefulness of MRI (magnetic resonance imaging) was evaluated in the diagnosis of the mediastinal invasion of esophageal cancer. MR examination was performed in 30 subjects without esophageal diseases and 23 patients with esophageal cancer. Normal esophagi and cancers were well visualized using T1-weighted image. In the axial section, every normal esophagus was contact to the aorta in the angle of less than 30 degree of the aortic circle. When the contact angle was less than 30 degrees, the stage of the cancer was below a1. When the angle was 30 degrees or greater, the stages were ranged from a0 to a3. In the oblique section orthogonal to the contact plain between the cancer and the aorta, the depth of the aortic invasion could be estimated. The sagittal scan was also helpful in the diagnosis of the invasion to trachea, left main bronchus and left atrium. PMID- 2325274 TI - [CT guided selective pneumomediastinography in thoracic imaging]. AB - We established new approaches for CT guided selective pneumomediastinography; paravertebral, pretracheal and anterior mediastinal approaches. CT would seem to be useful method for assessing the invasion to the neighboring structures in the thoracic neoplasms. But scanty fat in mediastinum often interferes with correct evaluation of mediastinal structures in conventional CT. Pneumomediastinal CT with our methods overcomes the weak point and provides additional information to enable exact diagnosis. The feasibility and security of these methods were confirmed through applying to many cases. Based upon these results, selective pneumomediastinal CT would be considered to be advantageous and advisable on the CT diagnosis in thoracic imaging. PMID- 2325275 TI - [Ultrafast CT scanner; preliminary experience in Japan]. AB - We evaluated the usefulness of Ultrafast CT scanner C-100 (UFCT) in 30 patients' clinical practice. UFCT was very useful not only for cardiac studies but for other body organs' studies. Simultaneous multilevel ultrafast scans of UFCT enabled us to analyse cardiac ventricular motion not only by the ejection fraction but by the change of wall thickness. We could get ultra-early contrast phase images (within one minute images from contrast medium injection start) of contiguous 15, 1 cm interval levels by high quality single slice mode of UFCT. These ultra-early phase images and late phase images would be helpful for tissue characterization. PMID- 2325276 TI - [Evaluation of aortic dissection by ultrafast computed tomography]. AB - We report usefulness of ultrafast CT (UFCT) in evaluation of aortic dissection, according to the results of examination of 51 patients. By volume mode study of UFCT, aortic dissection was diagnosed in all patients. Fine structures such as intimal tear and ulcer-like projection were depicted in detail. Pulsatile movement of true and false channels was detected by cine study. Precise flow analysis of both channels was available by flow mode study of UFCT. In morphological and functional assessment of aortic dissection, UFCT is superior to conventional scanners, and may be preferable to DSA or MRI. PMID- 2325277 TI - [Computed tomography for the diagnosis of thrombosed aortic dissection with extravasation]. AB - Four cases of thrombosed aortic dissection with extravasation demonstrated by CT were presented. In CT diagnosis for this type of dissection, cautions should be employed not only in an inhomogenous density area in the mediastinum and pleural cavity but also in the presence of deviation of intimal calcification and relatively high density area of crescent shape in aortic wall on plain CT. PMID- 2325278 TI - [Airbronchogram sign in small peripheral bronchogenic carcinomas]. AB - 18 bronchogenic carcinomas (16 adenocarcinomas, one squamous cell carcinoma, and one large cell carcinoma) in 17 patients and the control group (benign nodules) were examined with high resolution and thin section CT. Thin-section CT images showed airbronchogram or airbronchiologram in 63%, multiple small cavitations in 63%, and heterogeneous densities 50% of the adenocarcinomas with excellent spatial and contrast resolution. Airbronchogram or airbronchiologram was not seen in other types of bronchogenic carcinomas and benign nodules. Therefore, demonstration of airbronchogram or airbronchiologram in nodular lesions can make the CT diagnosis of small peripheral bronchogenic carcinomas, especially adenocarcinomas. PMID- 2325279 TI - [CT in eosinophilic granuloma of the lung]. AB - We analyzed the chest CT findings in nine patients with biopsy-proven eosinophilic granuloma. Multiple cystic lesions with relatively thin walls seems characteristic of this disease. Small nodular lesions and increased density were observed in many cases. Pleural or subpleural lesions were found in all cases. In seven cases, the distribution of the lesions were predominantly in the upper or upper and middle lung fields. In the remaining two cases however, lesions were found homogeneously throughout the whole lung. In order to analyze the site of the lesions in the secondary pulmonary lobule, a specimen obtained from an open lung biopsy was inflated and fixed using fixative by Heitzman's method. Observation of the slices of the specimen by dissection microscope and their soft X-ray radiographs demonstrated that the lesion existed in the central area of acini. However, CT of the patient before open lung biopsy didn't showed centriacinar distribution. The disparity is because a certain number of lesions lobule is necessary to identify the centriacinar pattern by CT. PMID- 2325280 TI - [CT of hypersensitivity pneumonitis]. AB - High resolution computed tomography (CT) was applied to seven patients with hypersensitivity pneumonitis clinically confirmed. The CT findings include; (1) granular pattern with acino-centric distribution, (2) increase in density of haziness in the lung fields, (3) multiform high density areas, and (4) "subpleural curvilinear shadow" localized posteriorly. Of these findings, which severally varied degree during clinical course, the haziness showed the most remarkable fluctuation. It was especially of interest that the relapsed haziness distributed quite in the same regions. High resolution CT may be an effective adjuvant tool for hypersensitivity pneumonitis when applied to the opportune evaluation through the clinical course. PMID- 2325281 TI - [Studies of CT images of bronchial tuberculosis, in reference to its pathogenesis]. AB - CT images of 18 patients with bronchial tuberculosis were studied and pathogenesis of the disease was analyzed on the basis of CT findings. Characteristic CT findings, observed in 15 cases, were thickening of bronchial wall and/or swelling of adjacent pulmonary arteries in peripheral part of bronchial tuberculosis lesion. In 11 of these 15 cases, observed pulmonary cavity and/or large tuberculosis lesions at the periphery of the above-mentioned CT findings, were considered to develop to the direct extension from parenchymal tuberculosis. Other 4 cases showed the above-mentioned characteristic CT findings, but without parenchymal lesions, the pathogenesis of the disease remained undetermined. In remaining 3 cases, neither characteristic CT findings nor remarkable parenchymal lesion was noticed. One of them was clarified by bronchoscopic examination. PMID- 2325282 TI - [CT of gold pneumonitis]. AB - We experienced five cases of gold pneumonitis. CT findings of four cases and pathological findings of an autopsy case were discussed. CT findings of gold pneumonitis could be classified as follow; (1) high density shadow of subpleural zone-BOOP suspected- (2) high density shadow along the broncho-vascular bundle (3) small cystic shadow of subpleural zone-UIP. Histological findings of an autopsy case revealed the fibrosis along the broncho-vascular bandle. A variety of radiologic and pathologic feature on the gold pneumonitis were seen. PMID- 2325283 TI - [Can radiologic features of community-acquired pneumonia presume etiologic agents?]. AB - During a one-year and nine months (from June 1987 to February 1989) survey of community-acquired pneumonia, we investigated in 130 patients if radiologic features presume etiologic agents. Incidences of etiologic agents are 21 (16%) pneumococcus, 18 (14%) mycoplasma, 14 (11%) tuberculosis, 12 (9%) hemophilus, and 54 (42%) unknown agents, respectively. In correlates of radiologic features and etiologic agents, alveolar shadows spreading bilateral lungs presume tuberculosis and pneumococcal pneumonia. Lobar distributing alveolar shadows presume pneumococcal, mycoplasmal tuberculous diseases and other agents, equally. Segmentally distributing shadows presume pneumococcal and mycoplasma pneumonia. Radiologic subgrouping features of alveolar shadows composed of acinar, lobular, and lobar shadows did not presume specific agents. Centrilobular (peribronchiolar) shadows suspect hemophilus infections. Pleural fluid accumulations suspect tuberculosis and anaerobic infections and cavitary shadows, tuberculosis, respectively. Radiologic features can presume etiologic agents. PMID- 2325284 TI - [Analysis of 123I IMP retention in the lung and application to the diagnosis of lung disease]. AB - The movement of N-isopropyl-p[123I] iodoamphetamine (I-123 IMP) in the lungs was studied. The half time of I-123 IMP release (T 1/2) was delayed in the fibrosis and the sarcoidosis. There was a relation between the prolongation of T 1/2 and the radiographic finding. It was considered that T 1/2 was useful for the objective estimation of the change in the lungs. The adsorption of I-123 IMP to the alveolar cells was much higher than to the circulating leukocytes. It was considered that the accumulation and retention of I-123 IMP in the lungs had relation to the alveolar cells. PMID- 2325285 TI - [Emergency perfusion lung scan for pulmonary embolism]. AB - Six cases of pulmonary embolism were reported. As pulmonary embolism often becomes critical condition, early diagnosis and medical treatment is need. Perfusion lung scan for pulmonary embolism may be useful for a diagnosis and evaluation of the degree of its disease and therapeutic value. PMID- 2325286 TI - [The role and clinical value of thallium-201 myocardial scintigraphy in ischemic heart disease]. AB - To define the role and clinical value of thallium-201 myocardial scintigraphy in ischemic heart disease, 967 consecutive patients referred to our laboratory since 1985 were studied. The purpose of scintigraphy has changed from diagnosing myocardial ischemia to assessing myocardial viability with the progress of coronary angioplasty. At present, thallium-201 myocardial scintigraphy has become an indispensable noninvasive method for the management of patients with ischemic heart disease. PMID- 2325287 TI - [Clear visualization of the tracheobronchial tree in complex congenital heart disease using digital subtraction fluorography]. AB - We knew that digital subtraction fluorography (DSF) could clearly visualize the tracheobronchial tree by the respiratory movement. We applied DSF for 54 patients of complex congenital heart disease. In the visualization of the tracheobronchial tree, DSF was significantly superior as compared with the plain chest radiography (p less than 0.01). As this method needs to anesthetize patients to suppress their body movements, there might be some limitation to apply it for routine diagnostic workup. However, noninvasiveness and readiness of diagnosis justifies this method as an optional examination for confirming thoracic situs of complex congenital heart disease. PMID- 2325288 TI - [Thin-section computed tomography of the bronchi; 2. Right upper lobe and left upper division]. AB - Thin (2mm) section contiguous computed tomographic (CT) scans were obtained through the bronchi of the right upper lobe and the left upper division in 30 patients. All segmental bronchi were identified. The right subsegmental bronchi were identified in 100%, and the left subsegmental bronchi in 97%. The type of the orifice of the right bronchus was trifurcated (53%), the extension of B1 was apicoanterior (50%), and the size of B2b was equal to B3a (63%). The extension of the left B3 was subapicoanterior (38%), and the size of B1+2c was equal to B3a (62%). PMID- 2325289 TI - [A study of image processing in CR mammography; gradation processing]. AB - CR image is made by several kinds of image processing. Gradation processing is most important to make images among them and its type can be decided by the kinds of x-ray examinations. 1.2 G gradation processing is generally recommended for CR mammography by the CR maker, but it has not been fully studied that whether 1.2G was the ideal one or not to image masses and/or calcifications. So, we compared the image obtained by 1.2G gradation processing with one by 1.0 d gradation processing that we made about imaging sensitivity of them in 18 cases with breast cancer. 15 out of 18 cases had good mass images and all of 6 cases showed good calcified images in the latter condition due to its high declination ( = gamma). So, we have concluded that 1.0 d gradation processing was better than 1.2G in CR mammography. PMID- 2325290 TI - [Gallium scintigraphy of a malignant lymphoma of the parotid gland]. PMID- 2325291 TI - [Current status and the future of brachytherapy (2)]. PMID- 2325292 TI - [Interactions between radiation and substances (2). Electron rays]. PMID- 2325293 TI - [Diagnostic imaging of pulmonary lymphangiomyomatosis; especially the correlation of CT finding and pathological finding]. AB - CT findings of pulmonary lymphangiomyomatosis were composed of diffusely arranged reticular and cystic appearances with mildly increased density. These correlated with histological increased smooth muscle cells, emphysematous change and dilated lymph vessels. PMID- 2325294 TI - [A case of lung torsion; migration of the atelectatic right upper lobe]. AB - A 67-year-old man with right upper lobe atelectasis due to squamous cell carcinoma showed positional change of the atelectatic lobe on plain chest radiograph, CT, and fluoroscopic observation. It was considered as lung torsion. PMID- 2325295 TI - [A case of sudden death from massive hematemesis due to rupture of an atherosclerotic aneurysm into the esophagus]. AB - A 86-year-old woman was admitted to our hospital following vomiting of a small amount of blood. On the 8th hospital day, the patient suddenly died of massive hematemesis. Autopsy disclosed thoracic aortic aneurysm with esophageal fistula. PMID- 2325296 TI - [Changes in blood coagulation and fibrinolysis following endoscopic injection sclerotherapy]. AB - Changes in blood coagulation and fibrinolysis were investigated in twenty seven patients with esophageal varices, who underwent endoscopic injection sclerotherapy (EIS) with 5% ethanolamine oleate with meglumine amidotrioate (EOMA), 1% Aethoxyskererol (AS) and pure ethanol. Changes in platelet aggregation between before and just after EIS were also investigated. Results obtained were as follows. 1) Remarkable changes in blood coagulation and fibrinolysis were observed in twenty patients, who underwent EIS by intravariceal injection combined with paravariceal injection. The patients showed significant change in factor XIa-alpha 1 antitrypsin complex as a result of destruction of the endothelium of varices, caused by the sclerosants. On the other hand, no significant changes were observed in seven patients, treated by paravariceal injection alone. 2) These changes were different from those observed in DIC because they were transient without bleeding tendency or multiple organ failures. 3) Paravariceal injection was suitable for EIS in the patients with very poor liver function. 4) Platelet aggregation was not elevated by EIS. PMID- 2325297 TI - [Chronic gastritic changes induced in rats after pyloromyotomy and per os administration of acetic acid-glycerin]. AB - We have experimentally studied whether or not repeated episodes of acute gastric mucosal lesions can induce chronic gastritic changes. Rats received pyloromyotomy and repeated per os administration of acetic acid-glycerin. Gastric mucosal lesions thus induced were studied histopathologically in cardiac glandular areas using morphometric analysis. It was found that pyloromyotomy induced fibrosis between the bottom of the gland and muscularis mucosa. On the other hand, the per os administration of acetic acid-glycerin induced hyperplastic change of mucous neck cells. They were increased in number and in size. Distribution of mucous neck cells were distended vertically to the mucosal surface and towards the bottom of the gland. Greater the amount of acetic acid-glycerin administration, stronger the changes of mucous neck cells, i.e., the distended zone of mucous neck cells spread more and more from the cardiac area. Parietal and chief cells were decreased in number in the course of the mucous neck cell hyperplasia. Branching of glands was occasionally seen in rats receiving greater amount of acetic acid-glycerin. It was concluded that there are basic structural similarity between the gastric mucosal changes induced by repeated episodes of acute gastric mucosal lesions and the change seen in human chronic gastritis. Thus acute gastric mucosal lesions can be one of the cause of chronic gastritis. PMID- 2325298 TI - [Immunohistochemical studies of ulcerative colitis--expression of HLA-DR antigen by colonic epithelium and the role of dendritic cells in the lamina propria]. AB - In 27 patients with ulcerative colitis the colonic mucosa was analyzed by an immunohistochemical technique. A quantitative evaluation for lymphocyte subsets shows significantly-increased numbers of CD3+ cells, CD4+ cells, CD8+ cells and Leu7+ cells in ulcerative colitis cases of histological grades 4 and 5 by Matts's classification comparing to controls. However, CD4/CD8 ratio in each histological grade of ulcerative colitis was similar to that in normal controls. The HLA-DR antigen on the colonic epithelium was frequently expressed in patients with grades 3 to 5 (84.2%), and in active patients (88.9%). The antigens were also expressed on the lamina propria mononuclear cells, which coincided with the distribution of S-100+ dendritic cells. Moreover double staining for S-100 antigen and IL-2R antigen revealed that most of the S-100+ dendritic cells were also IL-2R positive. These findings seem to provide evidence for the important role of lamina propria dendritic cells in the immunological pathogenesis of ulcerative colitis. PMID- 2325300 TI - [Group specific component protein (Gc) in patients with acute hepatic necrosis]. AB - We studied the clinical significance of serum Gc levels in the sera of patients with acute hepatic necrosis. Gc concentration were measured using an EIA in double sandwich technique with purified Gc as standard. Mean levels of serum Gc were 6.0 +/- 7.4 mg/dl in fulminant hepatitis, 20.8 +/- 13.6 mg/dl in acute hepatitis and 39.4 +/- 13.8 mg/dl in normal subjects respectively. There was slight correlation between Gc and PTT (P less than 0.05). In the observation of sequential study in patients with fulminant hepatitis, serum Gc levels of live cases elevated but those of dead cases slightly elevated, thereafter decreased. These results suggested that serum Gc levels was the useful marker as a grade of liver cell damage and a parameter of regeneration in liver cells. PMID- 2325299 TI - [Role of active oxygen species and lipid peroxidation in liver injury induced by ischemia-reperfusion]. AB - The role of superoxide and lipid peroxidation in liver injury induced by ischemia reperfusion was investigated in rats. Ischemic condition of the liver was created by applying small clamps to the right branch of portal vein and the right hepatic artery for 15 min. Clamping of hepatic artery and portal vein could decrease the hepatic blood flow to about 30% of that measured before the clamping. Levels of serum GPT and thiobarbituric acid (TBA) reactive substances in the liver tissue were significantly increased 30 min after the reperfusion following 15 min of ischemia. The increase in serum GPT and TBA reactants in the liver tissue was significantly inhibited by the treatment with superoxide dismutase combined with catalase. The treatment with allopurinol significantly inhibited the elevation of serum GPT levels and showed a tendency to inhibit the increase in TBA reactants in liver tissue. These results suggest that active oxygen species and lipid peroxidation may play an important role in the pathogenesis of ischemia reperfusion injury in the liver, and hypoxanthine-xanthine oxidase system may be one of the main sources of active oxygen species. PMID- 2325301 TI - [Long-term follow-up results in nonoperated patients with intrahepatic and predominant intrahepatic type of hepatolithiasis]. AB - In order to clarify therapeutic principles of hepatolithiasis associated with a variety of pathological conditions, we studied follow-up results in a term of 5 years after diagnosis in 29 nonoperated patients with intrahepatic gallstones. The patients including 14 males and 15 females underwent direct cholangiography for making diagnosis of the disease consisting of the intrahepatic type (I) and the predominant intrahepatic (IE). Out of the patients, 21 had good results in the follow-up and no one died from the disease or cholangiocarcinoma incidentally occurred. The follow-up results were closely related with the distribution and the location of gallstones in the liver and the grade of severity in clinical symptoms at the diagnosis. The unilateral lober type of the stone distribution had better follow-up results than the bilateral (P less than 0.01), and the peripheral intrahepatic bile duct type of the stone location did better follow-up results than the major (P less than 0.01). The pathological state of mild clinical symptoms showed better follow-up results than that of severe ones (P less than 0.05). The removal of coexisted extrahepatic bile duct stones by endoscopic papillotomy was effective for improving clinical symptoms. The conservative treatment in hepatolithiasis with the type I or IE was generally good in the follow-up results. The follow-up results were various, depending on the pathological conditions at the diagnosis. Accordingly, the treatment of hepatolithiasis must be selected in consideration of pathological conditions. PMID- 2325302 TI - [A case of Crohn's disease associated with an intramural sinus tract of the transverse colon demonstrated pathohistology]. PMID- 2325303 TI - [A case of Salmonella colitis occurred in ulcerative colitis]. PMID- 2325304 TI - [Successful vitelline arterial embolization for massive hemorrhage from Meckel's diverticulum]. PMID- 2325305 TI - [A case of idiopathic portal hypertension with "weeping willow" like appearance of intrahepatic bile ducts]. PMID- 2325306 TI - [Treatment of hepatic cyst by injection of minocycline hydrochloride]. PMID- 2325307 TI - [A successfully treated case of splenic abscess due to candidiasis associated with drug induced myelosuppression]. PMID- 2325308 TI - [A microspectrophotometric study of 'cancer in adenoma' of the colorectum]. PMID- 2325310 TI - [74th meeting of the Medico-Legal Society of Japan. 18-20 April 1990, Naha, Okinawa. Abstracts]. PMID- 2325311 TI - [30th meeting of the Japan Society of Chest Diseases. Tokyo, 9-11 April 1990. Abstracts]. PMID- 2325309 TI - [Possible role of oxygen-derived free radicals on the development of cysteamine induced duodenal mucosal injury in rats]. PMID- 2325312 TI - [Studies on pyospermia in male infertility]. AB - Among 670 infertile men, 72 were diagnosed as pyospermia according to our criteria. i.e., WBC greater than or equal to 10/hpf semen. The sperm motile efficiency index (SMEI) which indicates the rate of progressively motile sperms, was significantly low in pyospermic group compared with that of non-pyospermic men (WBC less than 5/hpf semen). From the result of split ejaculation, a major cause of pyospermia was supposed to be chronic prostatitis. The SMEI was decreased immediately after addition of the neutrophils and granulocyte elastase to semen. The mean value of granulocyte elastase in pyospermic group was 2859.6 micrograms/L, whereas that of non-pyospermic men was 131.6 micrograms/L. In summary, granulocyte elastase in seminal plasma may be a cause of inhibition of sperm motility in pyospermic state. PMID- 2325313 TI - [Clinical study on recurrence of urinary tract lithiasis of ESWL]. AB - During the 4 year period from September 1, 1984 through August 31, 1988, a total of 1,866 patients with calculi of the urinary tract (125 patients had bilateral calculi) were subjected to extracorporeal shock wave lithotripsy (ESWL) with a DORNIER HM3 ESWL apparatus. Follow-up was performed factor 1,056 cases 3 or more months after complete elimination of the calculi, and data were obtained for 343 of them. Lithiasis was found to have recurred after ESWL in 30 cases, with a recurrence rate of 11.1%. Recurrence was seen in 16.9% of cases with multiple calculi and 6.5% of cases with a single calculus. The difference was statistically significant. Surgical removed of calculi or spontaneous discharge of calculi had been experienced in 50.0% of the recurrent cases and 27.8% of the non recurrent cases. The difference was also statistically significant. Stone size, stone location and urinary tract infection were unrelated to the recurrence. PMID- 2325314 TI - [Experimental study of the viability of warm ischemic kidney. Relationship between ATP value in renal tissue by isotachophoresis and serum pyruvic acid to lactic acid ratio (P/L ratio)]. AB - The viability of preserved kidney is considered to be evaluated by mitochondrial function. We used the three experimental conditions of WIT 60 minutes (group I), 90 minutes (group II), and 120 minutes (group III) using rabbit. We measured the ATP value of renal tissue as a direct method before ischemia (control), immediately before recirculation, and at one hour, two hours, one day, two days, four days and seven days after recirculation, using isotachophoresis (Tachophor LKB 2127), and as an indirect method, serum pyruvic acid, lactic acid and LDH values were measured simultaneously. The ATP value in groups I, II, and III before recirculation were 1/10 lower than controls. However, as WIT became longer, the recovery speed was diminished. The serum P/L ratio reflected the mitochondrial function in group III. (p less than 0.05) The measurement of ATP value by this method, although it is somewhat invasive, is a useful method with a simple technique and a short analysis time. The serum P/L ratio is considered not to reflect the mitochondrial function directly, but can be measured adequately in WIT 120 minutes. PMID- 2325315 TI - [Ultrastructure of cultured normal bladder transitional epithelial cell and BBN induced rat bladder tumor cell lines]. AB - A normal rat bladder transitional epithelial cell line and seven tumor cell lines cultured from tumor induced by 0.05% N-Butyl-N-4-hydroxybutyl-Nitrosamine (BBN) were established and a comparative study on the doubling time and Ultrastructure of the cultured cell lines was performed. 1. Seven cultured cell lines (TU-B1 1 7) were obtained from bladder tumors induced by the administration of BBN for 32 weeks. 2. The doubling time of the cultured tumor cell lines were 43, 24, 28, 24, 25, 31, and 45 hours, suspectively. 3. These cultured tumor cell line were inoculated subcutaneously into nude mice and transitional epithelial carcinomas differing in degree of differentiation were observed. 4. Horizontal and tangential sections of these cultured tumor cell lines were examined by transmission electron microscopy. The development of intracellular organella and the presence of microvilli on the surface of the cells were noted. Intracellular adhesion was poor but the morphological characteristics of bladder transitional epithelium with compressed vesicles and other intracellular structures such as desmosome and free ribosomes were observed. 5. By applying the attached collagen gel method to our cell lines, it was possible to obtain cultured rat epithelial cells with the same morphology as in vivo, in addition to the tumor cell lines. 6. These cultured cell lines of normal rat transitional epithelium appear to be useful a experimental models with which one could clarify the function of the transitional epithelium and the mechanisms of bladder carcinogenesis. PMID- 2325316 TI - [Tumor factors concerned with primary culture of transitional cell carcinomas]. AB - We investigated retrospectively tumor factors such as tumor organ, method of tumor collection, tumor morphology and grade, concerned with primary cultures of transitional cell carcinomas of bladder, renal pelvis and ureter. Moreover, we investigated whether chemotherapy before tumor collection influence on the success rate of primary culture. After mechanical disaggregation of specimens from 42 bladder cancers and 11 renal pelvic or ureter cancers, monolayer cultures were carried out. When epithelial growth or colony-formation was observed, we determined that primary culture was succeeded. In total 30 primary cultures out of 53 (56.6%) were successful and tumor organ or method of tumor collection did not influence primary cultures. The success rates in the groups of papillary tumors and non-papillary tumors were significantly different (72.4% and 37.4%, respectively). Culture was more successful with grade 1 tumors. Although intravesical chemotherapy before tumor collection did not influence the success rate of primary culture, one-shot intra-arterial infusion chemotherapy made it worse (p less than 0.05) and it was concerned with histopathological effects according to the classification of Shimosato and Oboshi. PMID- 2325317 TI - [Study on chemosensitivity of colony forming cells]. AB - We suspect a difference between the effective rate of human tumor clonogenic assay (HTCA) and that of clinical chemotherapy against renal cell carcinoma. We investigated the sensitivity of ACHN, the cell line of renal cell carcinoma, and its colony forming cells (dividing cells) obtained on double soft agar against vincristine sulphate (VCR). In addition, PC-3, a cell line of prostatic carcinoma, and HeLa, cell line of cervicar carcinoma, were investigated. We obtained the results that each colony forming cells had higher sensitivity than each parent cells against VCR in the growth activities and the DNA synthesis measured by the uptake of 3H-thymidine. Because the cells targeted by HTCA are dividing cells, they are oversensitive compared with the true sensitivity of tumors. PMID- 2325318 TI - [Thoracic duct drainage pretreatment in living related kidney transplantation- long-term results of low dose steroid and azathioprine immunosuppression]. AB - The long term results of 28 HLA 1-haploidentical donor kidney transplant recipients receiving preoperative lymphocyte deletion through thoracic duct drainage and low dose of steroid and azathioprine immunosuppressive treatment were presented. The number of removed lymphocytes was 129.9 +/- 38.1 x 10(9) (mean +/- SD) and the duration of thoracic duct drainage pretreatment was 35 +/- 4 days. Graft survival was 96% at 3 months through 2 years, 89% at 3 years and 84% at 5 years. Patient survival was 100% at 3 months through 2 years and 96% at 3 years through 5 years. Fifteen acute rejection crises were observed in 13 patients within the first 3 months postoperatively. There was no irreversible rejection in the first 3 months. Four chronic rejections were observed in 4 patients. Life-threatening infectious disease was observed in 5 patients, diabetes mellitus in 2 and cataract in 4. These results indicated that the reduction of the dose of steroid in post transplant period might have beneficial effects on the long term graft survival of HLA 1-haploidentical kidney transplant patients receiving TDD pretreatment and the conventional immunosuppressive treatment. PMID- 2325320 TI - [Clinical study on 32 patients who underwent parathyroidectomy at Osaka City University Hospital]. AB - We retrospectively reviewed 32 patients who underwent parathyroidectomy at our hospital for the last fourteen years. 1) Clinical appearance of primary hyperparathyroidism was in younger age in women. 2) In previous history or at the time of PTX, 9 patients had malignant tumors including 6 thyroid cancers, 36% of the patients with out bone related symptoms had a remarkable decrease in bone mineral content. 3) After PTX, none of patients had recurrent urolithiasis and bone mineral content of all patients was significantly increased in a short time. In addition, upper GI complaints were improved, or hypertension was partially normalized. However, renal insufficiency remained unchanged. 4) In preoperative localization study, Ultrasound sonography (US) demonstrated the best accuracy rate of 88% when only one gland was involved. US was able to detect multiple gland involvement only in 20% of 5 cases. 5) Hypercalciuria was recognized as one of the risk factors of stone formation in patients with primary hyperparathyroidism. PMID- 2325319 TI - [Thoracic duct drainage pretreatment and low dose cyclosporine and low dose steroid immunosuppressive treatment in living related kidney transplantation]. AB - The results of 20 HLA 1-haploidentical donor kidney transplant patients treated with preoperative lymphocyte deletion through thoracic duct drainage and low dose of cyclosporine and steroid immunosuppressive therapy, were presented. The number of removed lymphocytes was 114 +/- 36 X 10(9) (mean +/- SD) and the duration of thoracic duct drainage was 35 +/- 7 days. Graft survival was 100% at 3-9 months and 89% at 1-2 years after transplantation. Patient survival was 100% at 3-9 months and 89% at 1-2 years. A patient died from lung cancer (adenocarcinoma) in the 9th posttransplant month. Acute rejection was not seen in 20 patients during the first 3 months. Life-threatening infectious disease was never seen either. Diabetes mellitus was observed in 1 patient. No other complications were observed. These results indicated that thoracic duct drainage and low dose cyclosporine and steroid postoperative immunosuppressive treatment might yield complete success in HLA 1-haploidentical kidney transplant patients. PMID- 2325321 TI - [Clinical experience with ESWL with new Dornier lithotripter MPL 9000]. AB - In June 1988, the new type of the lithotripter MPL 9000 (Dornier), which was the first interdisciplinary lithotripter for treatment of urinary and biliary calculi, was installed at the Shakai Hoken Chukyo Hospital. MPL 9000 has some features which enable one to treat with low range of shock wave energy and without anesthesia due to the enlarged aperture of the ellipsoid (210 mm), and locate the stone by computerized two ultrasound probes (coaxial, lateral). Unlike HM-3, the water bath is not used: shock wave is shot through the water cushion. From June to November 1988, 35 patients suffering from 64 urinary calculi were treated. The majority represented caliceal (75%) and pelvic (17%) stones, whereas 5 calculi were treated in the upper and lower ureter. Twenty-four patients were treated in one session and 11 patients needed additional sessions. The given number of shock waves was between 1337 and 3050 per one session and averaged 2403 with low generator voltage (15-18 kv). Twenty sessions (42%) were given without any medication and other 28 sessions (58%) were under analgesia (Pentazocine, i.v.) for the pain complained during the treatment. The rate of successful disintegration (less than 5 mm) was 88%. After the 1-month followup, 47.1% were free of stone, and 62.1% were free after the 3-month. Four patients had arrhythmia and one patient was with a subcapsular renal hematoma. We have concluded that this lithotripter is useful to treat upper and lower urinary tract calculi, in particular radiolucent ones in high risk patients because it is applicable without anesthesia. PMID- 2325322 TI - [Neurogenic bladder in patients with cervical cord compression disorders]. AB - Bladder and urethral functions were evaluated urodynamically in 62 patients with cervical cord compression disorder caused by either ossification of the posterior longitudinal ligament of the cervical spine (32 patients), cervical spondylosis (14 patients), prolapsed cervical intervertebral disc (14 patients) or cervical spinal canal stenosis (2 patients). The patients included 46 males and 16 females with average age of 57 years (range 39 to 73 years). Symptomatic organic infravesical obstruction was excluded by physical and radiographic examination. Cystometry revealed preoperative neurogenic bladder in 22 patients (35%) including overactive detrusor in 10 patients (45%) and underactive in 6 (27%). Twenty-one of them underwent electromyographic examination of external sphincter and 14 (67%) had overactive sphincter. Bladder and urethral functions appeared to be impaired in association with myelopathy of the pyramidal and spinothalamic tract of the cervical cord, because of high incidence of neurogenic bladder associated with positive Babinski's reflex and sensory disturbance at the perineal and lower extremity area. Furthermore, since many patients with deep sensory disturbance in the lower extremities had underactive detrusor, it appears likely that underactive detrusor was accompanied with myelopathy in the posterior funiculus of the cervical cord which mediates bladder proprioceptive sensation. Of twenty-two neurogenic bladder patients, seventeen underwent a cervical bone operation and eleven received postoperative urodynamic evaluation. The average interval from the operation to urodynamic evaluation was 1.6 months (range 1.1 to 2.3 months). Over half of the patients were found to be improved urodynamically as well as neurologically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325323 TI - [Histopathological analysis of incidental prostatic carcinoma by step section technique]. AB - In 244 cases treated by subcapsular prostatectomy during the period from April 1975 to December 1985, whole tissue specimens were prepared by a step section technique to examine them histopathologically in accordance with the handling agreement for prostatic cancer presented by the Urologic Society of Japan. The degree of differentiation, clinical stage of the disease, the size of the lesion and the distance to the margin were determined. Incidental carcinoma was found in 35 cases (14.3%), which increased with age. There were 21 cases of stage A1 and 14 cases of A2. Diffuse proliferation was found in 4 cases. Isolated carcinomatous focus was observed in 40 sites, and well, moderately, and poorly differentiated adenocarcinoma in 33, 3 and 4 sites respectively. The maximum diameter of cancer was below 5 mm in 80%, while the distance from the center of the carcinomatous focus to the surgical margin was within 3.5 mm in 905. Seven cases had plural lesions. These lines of evidence mentioned above may support carcinogenesis from the subcapsular region as well as multicentric origin of cancer. PMID- 2325324 TI - [Interferon-alpha producing capacities in prostatic cancer patients]. AB - Interferon-alpha (IFN-alpha) producing capacity was measured in 47 patients with prostatic cancer by whole blood assay. The mean IFN-alpha producing capacity of prostatic cancer patients was 3657 IU/ml, which indicated a significantly (p less than 0.005) lower value than that in healthy male aged 50 years or more. IFN alpha producing capacity in patients with Stage D disease was lower than that with Stage A, B or C. The higher the grade of the disease, the lower tended to be the capacity. A certain relationship was suspected between IFN-alpha producing capacity and the prognosis of each patient. In particular, in patients with prostatic cancer in Stage D, the prognosis was worse in low IFN-alpha producing capacity group (less than 3000 IU/ml) than in normal or high IFN-alpha producing capacity group (greater than or equal to 3000 IU/ml). It was considered that IFN alpha producing capacity might be useful in developing the prognosis of patients with prostatic cancer. PMID- 2325325 TI - [The muscular architecture at the ureteropelvic junction in congenital hydronephrosis--a stereo-morphometric study]. AB - Ureteropelvic junctions surgically taken from twelve patients with congenital hydronephrosis were submitted to stereo-morphometric studies on the architectural changes of smooth muscle layer. The specimens were opened longitudinally along the ureteral axis, flatly extended on a board, fixed in formalin and embedded in celloidin-paraffin. Serial histological sections in parallel with the wall were prepared; the 3D muscular architecture, visualized in some cases by computer aided reconstruction, was simplified into vectors of bundles so that their arrangement might be expressed by a vector distribution. Deviation from the norm of architecture at the ureteropelvic junction was disclosed: Reduced muscles with increased connective tissues in four cases and disarrangement of bundles in eight cases, including two with predominantly longitudinal element, three with circular element and another three with irregular orientation. These abnormalities, probably reflecting abnormal maturation of muscles, appear to be related with the urinary obstruction in patients with congenital hydronephrosis. PMID- 2325326 TI - [Basic study of nephrotoxicity of antibiotics. II. Studies of the effect of antibiotics on lysosomal stability in rat kidneys]. AB - In order to assess the potential nephrotoxicity of antibiotics, effects of these agents on rat kidney lysosomal membrane were investigated in various conditions. Antibiotics were given to Wistar rats for 5 successive days. After nephrectomy rat lysosomes were separated and their membrane stability was examined by measuring the activities of acid-phosphatase. In addition, after separation of lysosomes from normal untreated Wistar rats, antibiotics were added in the incubation system to assess the in vitro effect of antibiotics. Effects of renal ischemia and the lysosomal membrane stabilizer (cortisol) were also examined. Aminoglycosides antibiotics (streptomycin, kanamycin, gentamycin), doxytetracycline, chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used for this purpose. It was clearly pointed out that aminoglycosides interfered with the lysosomal stability in vivo and in vitro. After a 60 minutes ischemia of the rat kidneys by clamping the renal arteries, effects of antibiotics on administration of 5 successive days on rat lysosomal stability were investigated. It was demonstrated that aminoglycosides also made the lysosomal membrane more unstable. Effects of the lysosomal stabilizer, cortisol, on rat kidney lysosomes were examined. Use of cortisol simultaneously with an antibiotic was more effective than that before and after it. PMID- 2325327 TI - [Clinical efficacy of recombinant interleukin-2 for renal cell carcinoma and the effect of blood transfusion upon the immune response of these patients]. AB - We studied the efficacy and safety of recombinant interleukin-2 (rIL-2: S-6820) for the treatment of renal cell carcinoma as well as the effect of blood transfusion upon the immune response of these patients. Among 14 cases of renal cell carcinoma treated by i.v. infusion of rIL-2, a partial response (PR) was achieved in one patient, 10 patients had no change, and in 3 had the disease progressed. The overall efficacy rate was 7.1%. However, the rate increased to 12.5% in cases with pulmonary metastases and to 14.3% in cases without any blood transfusion within a year before treatment with rIL-2. No severe side effects were observed, except for central nervous system disturbance in one case. During the rIL-2 therapy, LAK activity was suppressed in the transfused patients. On the other hand, NK activity was augmented in transfused patients to the same degree as in non-transfused cases. No significant changes of lymphocyte count and the subsets of peripheral blood lymphocytes were observed in either group treated with rIL-2. Anemia and radical nephrectomy did not affect the immune response in these patient. Thus, it appeared that blood transfusion altered the immune response in patients treated with rIL-2. However, it could not be concluded that transfusion definitely had an adverse effect on the clinical efficacy of rIL-2 for renal cell carcinoma. PMID- 2325328 TI - [Renal cell carcinoma and angiomyolipoma in tuberous sclerosis. Case report]. AB - The association of angiomyolipoma with renal cell carcinoma in tuberous sclerosis is extremely rare, although the relation between tuberous sclerosis and angiomyolipoma of the kidney is widely recognized. We report here a case of bilateral angiomyolipoma and renal cell carcinoma of the right kidney with tuberous sclerosis and demonstrate the diagnostic difficulties in distinguishing between these tumors. PMID- 2325329 TI - Production and development of calves from sexed-bisected bovine embryos. AB - Sixty-five chromosomal preparations from bisected bovine embryos were examined and 43 embryos (66.2%) with metaphase plates were observed; however, only 25 embryos (38.5%) were sexed. Fifteen of the bisected embryos sexed by chromosomal analysis were transferred to each of the 15 recipients, and 5 recipients became pregnant. Female calves were born on December 28, 1985, August 2, 1986 and July 18, 1988. The first female calf born from a sexed-bisected embryo (December 28, 1985) was the first case in Japan. The gestation lengths and birth weights of these calves were 277, 278 and 274 days, and 42.0, 44.0 and 37.0 kg, respectively. These two calves grew within the range of the "Standard developmental growth curve of the Holstein heifer" of the Japanese Holstein Association. The milk yield from 2 sexed-bisected cows were recorded. In the first cow (Case 1), she produced 8,575 kg of milk, 5.0% fat and 9.4% solids-non fat (SNF) per year. In the other cow (Case 2), her expected milk volume was 7,800 kg per year. Confirmation of parentage was done by blood typing, and certified by the Japanese Livestock Animal Improvement Association. PMID- 2325330 TI - Characterization of two monoclonal antibodies which recognize different subpopulations of chicken T lymphocytes. AB - Distribution among peripheral T lymphocyte subpopulations and biochemical properties of the chicken lymphocyte surface antigens defined by monoclonal antibodies (mAbs) Lc-4 and Lc-6 were examined. Two-color immunofluorescence analysis revealed that Lc-4 and Lc-6 antigens were expressed on mutually exclusive subpopulations of peripheral T lymphocytes but not on B lymphocytes. Lc 4 mAb precipitated a polypeptide with apparent molecular mass of 35 and 65 kilodalton under reducing and non-reducing conditions, respectively. These results indicated that the antigen recognized with Lc-4 was closely similar in tissue distribution and biochemical property to mammalian CD8 antigen. PMID- 2325331 TI - Lactate dehydrogenase and creatine phosphokinase isoenzymes in tissues of laboratory animals. AB - The lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) isoenzyme distributions in tissues of the ICR mouse, Wistar rat, guinea pig and golden hamster were analyzed by histoelectrophoresis. Tissues obtained were as follows: liver, pancreas, stomach, small intestine, heart, femoral muscle, uterus, kidney, spleen, lymph node, cerebrum, spinal cord and erythrocyte. Histoelectrophoresis was for the direct analysis of LDH and CPK isoenzymes in the tissues and had high practical value compared with previous tissue-extraction methods. In tissues of the mouse, guinea pig and golden hamster, LDH isoenzymes showed five bands. In the rat, LDH isoenzyme was separated into four fractions. CPK isoenzyme showed three bands; BB, MB and MM. In some tissues, the MM band was separated into two sub fractions. PMID- 2325332 TI - Lithium in renal physiology. Utrecht, The Netherlands, April 26-27, 1989. Proceedings. PMID- 2325333 TI - History of the "lithium concept". PMID- 2325334 TI - Permeability characteristics and probability of lithium transport in the thin limbs of Henle's loop. PMID- 2325335 TI - Lithium clearance in healthy humans: effects of sodium intake and diuretics. AB - In summary, our experiments clearly demonstrate that lithium reabsorption occurs by frusemide- and bumetanide-sensitive reabsorption, but we have failed to identify the mechanism(s) responsible for the lower CLi and FELi in salt depletion. It is possible that some, as yet unknown, factor increases the activity of the Na, K, 2Cl cotransporter and, hence, increases lithium reabsorption in the thick ascending limb in salt-depleted subjects. However, it is equally possible that a fraction of proximal tubular reabsorption is inhibited by frusemide and bumetanide. If this is correct, CLi in humans are reasonable markers of proximal tubular function even in conditions of avid salt retention and in salt depletion, when fractional reabsorption of salt and water in the proximal tubules is enhanced. PMID- 2325337 TI - Lithium clearance in humans: effects of acute administration of acetazolamide and furosemide. PMID- 2325336 TI - Lithium clearance derived from the natural trace blood and urine lithium levels. PMID- 2325338 TI - Effects of bumetanide and ouabain on lithium transport in the distal nephron of dogs. PMID- 2325339 TI - Impairment of renal tubular acidification by lithium: a microperfusion study in the rat. PMID- 2325340 TI - Lithium in renal physiology: post-conference discussion and consensus. PMID- 2325341 TI - [The accommodation-convergence bar (A=C bar)]. AB - The accommodation-convergence bar was developed as a simple measuring and exercise instrument. For the ophthalmologist, it is a convenient means of measuring accommodation and convergence in the office, while patients can use it for home convergence and fixation exercises which they can monitor themselves. The A = C bar has also been used experimentally to eliminate the functional central scotoma in dyslexic children. PMID- 2325342 TI - [Technic and long-term results of cryogenic epilation in trichiasis and distichiasis]. AB - The present paper communicates the technique and results of cryoepilation in 1,690 cases (94% trichiasis and 6% distichiasis). Only nitrogen cryotherapy devices are totally suitable for this, and the spray freezing method is to be preferred. The IKG unit developed by the authors, which has proved successful in particular for tumor therapy, is also ideal for cryoepilation. It generates a very tightly bundled nitrogen spray jet, thus permitting isolated freezing of the lid margin. In about 95% of the cases permanent epilation is achieved without undue trauma. In 5% the condition described by Fraunfelder as "secondary trichiasis" develops. Ocular pemphigoid is not a contraindication to cryotherapy. PMID- 2325343 TI - [Cytostatic and immunosuppressive treatment of ocular Behcet syndrome]. AB - Ocular symptoms of Behcet's syndrome in 16 patients and the results of cytostatic and immunosuppressive therapy with cyclosporin A (6 patients), chlorambucil (6 patients), and a combination of cyclophosphamide and procarbacin (4 patients) are described. The clinical course and therapeutic outcome were compared to the patients' visual acuity and the duration of the disease prior to institution of cytostatic therapy. Average follow-up was 4.6 years, maximum 9 years. The principal ocular symptom in all patients was hemorrhagic, occlusive periphlebitis. Other symptoms, in descending order of frequency, were chorioretinitis, iridocyclitis, complicated cataract, secondary glaucoma and exudative retinal detachment. The patients in whom cytostatic therapy was instituted no later than 6 months after onset of the disease showed an improvement in or stabilization of visual acuity, as well as a clear reduction in signs of intraocular inflammation and frequency of recurrence. No improvement in visual acuity or ocular symptoms was achieved in cases where the disease was very advanced, despite cytostatic-immunosuppressive therapy. The results support early institution of immunosuppressive therapy in cases with Behcet's syndrome where severe, irreversible damage has not yet occurred and in which vision is threatened in both eyes. However, due consideration must be given to the potential risks of immunosuppressive therapy, in particular the risk of a malignant tumor. PMID- 2325344 TI - [The extent of bacterial contamination of keratoplasty donor eyes post mortem]. AB - In order to determine the initial bacterial contamination of corneal donor material the abraded epithelia from 125 donors, i.e., 250 globes, were examined immediately after enucleation. Of these, 49 (19.6%) were sterile, while 201 (80.4%) were contaminated. Monoinfection was identified in 174 globes and mixed infection in 27. The pathogen most frequently isolated was Pseudomonas aeruginosa. Neither the donor's age not the time elapsed between death and enucleation had any influence on the contamination rate. Prolonged hospitalization of donors leads to an increase in gram-negative bacteria. The necessity of antibacterial prophylaxis prior to keratoplasty is pointed out. PMID- 2325345 TI - [Coincidence of hypertensive changes of the eye fundus and regulation disorders of peripheral microcirculation: I--Skin]. AB - In cases of arterial hypertension, funduscopy is an established method of estimating systemic vascular lesions. In this study the relation between the extent of retinal vascular changes and dynamic processes in the microcirculation of the skin was investigated by nailfold capillaroscopy in 88 patients. With increasing vascular changes a progressive loss of vasodilator reserve and transcutaneous partial pressure was observed (no morphologic changes--fundus hypertonicus II--fundus hypertonicus III). It thus appears possible to evaluate the functional state of the macro- and microcirculation by funduscopy. PMID- 2325346 TI - [Staphylococcal endophthalmitis following squint surgery]. AB - A 10-year-old boy was referred to the authors three days after bimedial faden operation (posterior fixation), with a purulent endophthalmitis in his right eye and visual acuity of LP. Systemic combined antibiotics "ad hoc", including cephalosporins and amikacin, were administered in combination with immunosuppressive doses of methylprednisolone after swabs had been taken for bacteriologic workup. Nine days after admission a pars plana vitrectomy was performed. Both the conjunctival swabs and the vitreous aspirate grew coagulase negative, gram-positive cocci with high colony counts. Traction retinal detachment developed, and 30 days after the squint surgery lensectomy and silicone oil instillation had to be performed. Visual acuity 3 months after squint surgery was RE cc 0.2. PMID- 2325347 TI - [Lymphogenic dissemination of an epibulbar melanoma]. AB - Conjunctival melanomas are considered to be malignant tumors, the prognosis of which depends on various factors such as the size and thickness of the tumor and the number of recurrences following excision. The authors report on a 47-year-old woman who, years after local excision of a recurrent limbal conjunctival melanoma, developed an epibulbar melanoma far from the site of the original scar. The authors attribute this recurrence to lymphogenic propagation. PMID- 2325348 TI - [Continuous profile perimetry]. AB - The present paper describes a modified form of profile perimetry. The brightness of a test mark moved at varying speed is increased, and as soon as it is supraliminal the examinee can press a button to reduce the brightness to subliminal again. The accuracy with which the threshold is determined is in the range of a few dB in 1-degree steps in the respective meridian. The reproducibility of the examination makes follow-up possible. A moderate loss of sensitivity can be recognized directly from the record, as can an increased short term fluctuation of the light difference threshold. Results in subjects with healthy eyes and persons with ocular pathology are described. Possibilities for improvement, in particular to save more time, are discussed. PMID- 2325349 TI - [Schizencephaly]. AB - Schizencephaly is a developmental disorder of the human brain caused by a defect of neuronal migration. We observed a 7 month old african boy suffering from nystagmus and hemiparesis. The neuroimaging reveals a large cleft in cortical and subcortical structures and typical changes of polymicrogyria. In the differential diagnosis encephaloclastic porencephaly should be considered. PMID- 2325350 TI - [Right-sided lung hypoplasia in a 13-year-old boy]. AB - Initially a right sided pulmonary hypoplasia was diagnosed in our patient at the age of 9 years. The previous years were characterized by recurrent pneumonia, bronchitis and daily coughing fits. Findings of the chest radiograph suggested the diagnosis of right sided hypoplasia. The right hemithorax was small with mediastinal structures being pushed to the right and a clearly reduced blood flow on the same side. DSA of the arteria pulmonalis showed hypoplasia of the right arteria pulmonalis and confirmed our diagnosis. In addition to that an obstructive airway disease was assessed by measurement of lung function. Since the time when the diagnosis was found our patient has inhaled DSCG and beta 2 adrenergic drugs and no surgical treatment has been required as there have been no further episodes of pneumonia. PMID- 2325352 TI - Dientamoeba fragilis infection, a cause of gastrointestinal symptoms in childhood. AB - Clinical and laboratory findings of 123 paediatric patients with infections due to intestinal protozoa were analysed. Dientamoeba fragilis (D.f.) was found in 102 cases. The other patients had infections with Giardia lamblia or mixed infections with several other protozoa. Acute and recurrent diarrhoea were the most common findings (56 cases), whereas abdominal pain was more common in children with chronic symptoms. Peripheral eosinophilia was present in 32% of the children with dientamoebiasis. Metronidazole, oxytetracycline, doxycycline, and erythromycin were the most effective drugs in the treatment of D.f. infections. The therapy led coincidentally to the sanitation of stools and elimination of abdominal complaints. The investigations underline the pathogenic role of D.f. in those children with gastrointestinal symptoms. Mixed infections of D.f. and Enterobius vermicularis suggest a vector bound transmission of D.f. PMID- 2325351 TI - [Acute chorea following heart surgery with hypothermia and total bypass]. AB - We report a 6 year old girl who developed acute chorea following cardiac surgery using hypothermia and total cardiopulmonary bypass. Rheumatic disease, cerebral embolism or hemorrhage were excluded. Cerebral hypoperfusion during surgery is the most probable cause for this neurologic event. Treatment with Tiaprid (Tiapridex) resulted in a rapid resolution of symptoms. PMID- 2325353 TI - [Recurrent acidosis with hypoglycemia in an infant: fructose-1,6-diphosphatase deficiency]. AB - A seven months old infant presented with recurrent episodes of acidosis and hypoglycemia triggered by fasting and febrile infections. The diagnosis of fructose-1,6-diphosphatase deficiency was made by demonstrating the enzyme deficiency in a liver biopsy specimen. Fructose-1,6-diphosphatase is a key enzyme of gluconeogenesis. Fructose-1,6-diphosphatase deficiency results in hypoglycemia and lactic acidosis during episodes of fasting. Diagnosis is made preferably by liver biopsy. Treatment includes elimination of fructose and sucrose from the diet and avoidance of fasting. Acute attacks are treated by intravenous infusion of glucose and bicarbonate if necessary. PMID- 2325354 TI - [Brain tumors in infants]. AB - 1975-87 there were 15 infants in the Childrens University Hospital of Zurich, cared for a brain tumor. In 3 cases the first symptoms were already present by birth. In our cases epileptic convulsions were the most common first manifestation of the tumor (40%). In most cases neither clinical symptoms nor EEG changes helped to localize the tumor. In one third of the cases the tumor was manifested with symptoms of increased intracranial pressure. In 11 children (73%) the tumor was localized supratentorially, in 3 cases in the cerebellum, in one case in the brainstem. 13 children were operated, without perioperative mortality. In 10 cases the tumor was radically extirpated, in 3 cases only a subtotal excision of the tumor was possible. PMID- 2325355 TI - Doppler measurement of cardiac output across prosthetic mitral valves. AB - In 46 patients with a normal functioning mitral valve prosthesis (15 St. Jude, 19 Medtronic Hall, 12 Hancock) cardiac output was measured by pulsed Doppler echocardiography across the valve prosthesis. Simultaneously cardiac output was determined by thermodilution or pulsed Doppler echocardiography in the left ventricular outflow tract (2.8 l/min-9.5 l/min). The prosthetic valve area was calculated using the pressure half-time method. Cardiac output was calculated by multiplying time-velocity integrals with the mitral valve area. Cardiac output measurements across the mitral prosthesis correlated significantly with thermodilution (r = 0.96, SEE = 0.400 l/min) and pulsed Doppler echocardiography flow measurements in the left ventricular outflow tract (r = 0.82, SEE = 0.679 l/min). The mean percent error of the Doppler transmitral flow measurement was 10.8%. Doppler transmitral flow underestimated cardiac output valves of more than 6.5 l/min in 6 of 7 patients. Cardiac output measurements across Hancock (SEE = 0.473 l/min) and St. Jude prostheses (SEE = 0.538 l/min) were more accurate than across Medtronic Hall prostheses (SEE = 0.847 l/min). Cardiac output can be calculated by pulsed Doppler echocardiography across normal functioning mitral prostheses. Due to the different flow dynamics the accuracy of cardiac output measurement depends on the prosthetic valve type. Reliable measurements of cardiac output can be performed across Hancock and St. Jude prostheses only. This method is limited in volume flow measurements across Medtronic Hall prostheses. PMID- 2325356 TI - Neurological outcome after a severe herpes simplex encephalitis treated with acyclovir and beta-interferon. Time course of intracranial pressure. AB - A severe herpes simplex encephalitis with documented intra-cerebral lesions and brain edema was treated successfully with acyclovir and beta-interferon. The increase in intracranial pressure during the second week was well controlled by ICP monitoring. Life-threatening pressure peaks were avoided through the use of thiopental, osmodiuretics, TRIS, and lidocaine. PMID- 2325358 TI - [Foundations for a new concept of oncology in general nursing education. More oncology in basic education]. PMID- 2325359 TI - [The advantages of dehydration for the dying--to die without tubing]. PMID- 2325357 TI - [Intestinal angiodysplasia as a cause of severe intestinal hemorrhage--report of 4 cases]. AB - Angiodysplasia of the small intestine alone cannot be differentiated histologically from hereditary hemorrhagic telangiectasia (Morbus Rendu-Osler Weber). Isolated localisation in the small intestine is rare and requires surgery in the event of massive bleeding. Four cases of bleeding from angiodysplasias of the small intestine in patients having undergone surgery at our institution over a ten-year period are presented. In three patients the particular intestine was resected. Two of these patients had an uneventful follow-up of even and ten years, one patient relapsed and was rehospitalized for surgical treatment. The fourth patient, who showed angiodysplasias scattered over the entire small intestine, had no further bleeding over a three-year period after transmural ligations of the lesions found by intraoperative endoscopical diaphany. PMID- 2325361 TI - [Regression: different visions, different responses]. PMID- 2325360 TI - [The background of complaints in old-age and nursing homes. To demand, to complain and deplore]. PMID- 2325362 TI - [Erwin Bohm's method for transient care. Nursing with hands in pocket]. PMID- 2325363 TI - [To serve the patient, and him only...]. PMID- 2325364 TI - [Cultural representation of mental disease--lessons from elsewhere]. PMID- 2325365 TI - [Nursing know-how]. PMID- 2325366 TI - [Research, the leaven of change]. PMID- 2325367 TI - [Cycle of continuing education in oncologic nursing. Necessary adaptations]. PMID- 2325369 TI - [Holistic nursing based on research]. PMID- 2325368 TI - [When the patient refuses to eat and to drink. Dehydration--is it necessary to intervene?]. PMID- 2325370 TI - Child abuse reporting in South Carolina, 1975-1987. AB - Child abuse continues to be a tremendous medical and social problem in South Carolina. Hundreds of children are injured each year and some are killed. Many injuries and deaths could have been prevented with timely intervention. Unfortunately the vast resources available in the fight against child abuse are of little value if primary health providers fail to notify the appropriate agencies. Improvements in education, detection, reporting and intervention are the only effective means of reducing the morbidity and mortality associated with child abuse and helping to eradicate it from society. PMID- 2325372 TI - Results of mammographic localization of occult breast cancer at a teaching community hospital. PMID- 2325371 TI - Combined pharmacologic and exercise stress myocardial scintigraphy: a practical method for assessment of potential cardiac ischemia in patients with limited exercise capacity. AB - A protocol for dipyridamole exercise stress testing with myocardial thallium scintigraphy has been used successfully for the evaluation of exercise or walking impaired patients. PMID- 2325373 TI - A new code of ethics: the principles of ethics of the South Carolina Medical Association. PMID- 2325374 TI - Ethics and ex parte discussions. PMID- 2325375 TI - Child abuse: new perspectives. PMID- 2325376 TI - Quantitative determination of stanozolol and its metabolite in urine by gas chromatography/mass spectrometry. AB - The amount of stanozolol and 3'-hydroxystanozolol in urine was determined after oral administration of stanozolol. A gas chromatograph/mass selective detector equipped with a capillary column was used for these determinations. The GC/MS was operated in the SIM mode, and m/z 581, 669, and 315 were monitored for stanozolol, 3'-hydroxystanozolol, and calusterone (internal standard), respectively. The detection limit was approximately 1 ng/mL for both steroids. The maximum excretion rate of stanozolol was reached in 8 h and the maximum of 3' hydroxystanozolol in 19 h. However, only 3% of the administered amount was recovered in urine. PMID- 2325377 TI - Urinary excretion of furazabol metabolite. AB - Furazabol, a newer anabolic steroid, is metabolized into 16-hydroxyfurazabol and excreted in urine. The presence of this compound in urine can be monitored with a GC/MS procedure. It can be incorporated into the general dope testing protocol for anabolic steroids. PMID- 2325378 TI - Analysis of bumetanide in human urine by high-performance liquid chromatography with fluorescence detection and gas chromatography/mass spectrometry. AB - Bumetanide is a potent diuretic. Its concentration in urine after therapeutic doses is in the low ng/mL range. A procedure using reversed-phase HPLC with fluorescence detection is described. Using this procedure, the authors have been able to measure bumetanide in a urine sample at 10 ng/mL with a signal-to-noise ratio of 7. Therefore, the detection limit is lower than this concentration. Confirmation is by a GC/MS procedure after methylating the diuretic. Derivatization is by extractive alkylation with tetrabutylammonium hydrogen sulfate as the phase transfer reagent and iodomethane as the methylating agent. PMID- 2325379 TI - Comparison of the GC/MS ion trapping technique with GC-FTIR for the identification of stimulants in drug testing. AB - The identification of banned stimulants in the urine of athletes is typically performed by gas chromatography with electron impact mass spectrometry (GC-EIMS). Derivatization is usually used to improve the chromatographic properties and to produce unique mass spectra for closely related compounds. Both gas chromatography with chemical ionization mass spectrometry (GC-CIMS) and gas chromatography with Fourier transform infrared spectroscopy (GC-FTIR) were compared for three test mixtures of stimulants. Both techniques were capable of supplying the necessary information for conclusive confirmation. However, the CI option on the ion trap mass detector (ITD) offers the most sensitive and fastest way for the confirmation of positive samples with detection limits of 1-10 ng. The GC-FTIR is from a chemometrics point of view more specific but needs 25-75 ng for a reliable spectrum. PMID- 2325380 TI - Drug testing in sports. PMID- 2325381 TI - Drug testing at the 10th Asian Games and 24th Seoul Olympic Games. AB - Drug testing (doping test) procedures in the 1986 10th Asian Olympic Games and 1988 24th Seoul Olympic Games are reported. The International Olympic Committee Medical Commission (IOC-MC) conducted its first doping tests at the 1968 Olympics in Grenoble. With the guidance of the International Olympic Committee (IOC), the Olympic Council of Asia (OCA) introduced doping tests at the 1986 10th Asian Olympic Games in Seoul, Korea, September 21st to October 5th, 1986. 585 samples were tested at the Doping Control Center, Korea Advanced Institute of Science and Technology (DCC/KAIST), for stimulants, narcotics, anabolic steroids, and beta blockers by gas chromatography/mass spectrometry, high pressure liquid chromatography, and fluorescence polarization immunoassay. These tests covered about 100 different drugs and another 400 as metabolites in addition to pharmacologically related substances. For the Seoul Olympic Games from September 17 to October 2, 1988, the IOC-MC with the DCC/KAIST conducted doping tests on 1601 samples for stimulants, narcotics, beta-blockers, diuretics, and anabolic steroids using GC, HPLC, GC/MSD, GC/MS, LC/MS, and TDx. PMID- 2325383 TI - Analysis of anabolic steroids using GC/MS with selected ion monitoring. AB - This study describes the use of gas chromatography/mass spectrometry with selected ion monitoring to screen 18 anabolic steroids banned by the International Olympic Committee. These anabolic steroids are analyzed in two fractions depending on their excretion pattern: nonconjugated (free) or conjugated fraction. The wet procedure of extracting steroids from urine consists of an initial isolation of lipophilic compounds on a column packed with Amberlite XAD-2 resin, followed by enzymatic hydrolysis with beta-glucuronidase from Escherichia coli. After extraction, the hydrolyzed steroids are derivatized to the corresponding trimethylsilyl ethers. The derivatized steroids are analyzed by gas chromatography/mass spectrometry with selected ion monitoring of their characteristic ions. It takes 12 and 26 min to run GC/MS and edit the raw data for nonconjugated and conjugated fractions respectively. PMID- 2325382 TI - Systematic analysis of diuretic doping agents by HPLC screening and GC/MS confirmation. AB - The simultaneous analysis of diuretic agents by reversed-phase liquid chromatography with a diode-array detector (DAD) was performed by using a gradient elution with acetonitrile and phosphate buffer on a Hypersil-ODS column. For the spiked urine the extraction recovery of solid-phase extraction (SPE) using Sep-Pak C18 cartridge was compared with that of liquid-liquid extraction (LLE) with diethyl ether at various pH. The standard calibration curves were linear from 0.20-20.0 micrograms/mL for all diuretic agents except amiloride, 1.0 20.0 micrograms/mL, and the detection limit was about 0.2 micrograms/mL for 3 mL of urine, except that of amiloride, which was 1.0 micrograms/mL. The confirmation analysis was performed by gas chromatography/mass spectrometry (GC/MS) following methylation. The characteristic mass fragment ions obtained by electron-impact (EI) ionization (70 eV) provided identification of each diuretic agent. PMID- 2325384 TI - Mass spectrometry of methyl and methyl-d3 derivatives of diuretic agents. AB - Methyl and methyl-d3 derivatives of 10 diuretic agents were analyzed by electron impact mass spectrometry. The mass spectra and mass fragmental pathways were investigated with deuterated methyl isotopes. PMID- 2325385 TI - Knowledge and attitudes of health care workers about AIDS and HIV infection before and after distribution of an educational booklet. AB - Hospital workers (509) in a health authority were surveyed, and asked if they were in contact with HIV positive or AIDS patients; about their perception of risk; of their knowledge about and attitudes towards HIV and AIDS problems at work; and their desire for more information about AIDS and HIV. Overall scores for level of knowledge and attitudes were calculated; clinical workers scored better than non-clinical workers. Following the first survey, an information booklet was distributed to all health authority staff and after distribution, 232 staff were surveyed again. In this group (the follow-up group), there was a reduction in perceived risk, an improvement in the level of knowledge and in attitudes, and a reduction in the desire for further information. The group who initially had the least level of knowledge and most unfavourable attitudes (non clinical workers) were the group who improved most. PMID- 2325386 TI - Needle-stick injuries in medical students. AB - A standard questionnaire was used to assess the experience of needle-stick injury in 151 undergraduate medical students, during the previous 10 months. Eighty-two injuries were reported in the 95 questionnaires which were returned. Fifty-one of these took place during venepuncture; of these 26 whilst resheathing a needle. Seventy-two per cent of students resheathed used hypodermic needles, but their rate of injury did not differ significantly from the rate in those who did not resheath. The remaining 31 injuries occurred during surgical procedures. There was a significantly lower rate of injury in those who had earlier been advised to have hepatitis B immunization. PMID- 2325387 TI - Hepatitis B markers in ambulance personnel in Lancashire. AB - One hundred and seventy-nine ambulance personnel working in Lancashire were tested for markers of past or current hepatitis B. None was currently infected but two (1.1 per cent) had had hepatitis B in the past with full recovery. Thus, the prevalence of past hepatitis B was within the range observed for blood donors in the UK. PMID- 2325388 TI - Research in occupational medicine--thriving or dying? PMID- 2325389 TI - Occupational health research: academic activity or idle ideas? PMID- 2325390 TI - Education, research and occupational medicine. PMID- 2325391 TI - Occupational health research--looking to the next decade. PMID- 2325392 TI - Incidence of mesothelioma in Glasgow 1981-1984. AB - Considerable public concern exists about the effects of exposure to asbestos both at the workplace and in the general environment. In addition, the recording of mesothelioma in health registers is questionable both in terms of accuracy and completeness. This paper compares nine different sources of data for mesothelioma in an attempt to establish the true incidence of the disease in the geographical area of the Greater Glasgow Health Board between 1981 and 1984. Although 113 cases were identified, no single source identified more than 86 per cent of this total, thus presenting a case for a special mesothelioma register. A questionnaire-based study of the occupational exposures and residential histories of the cases was also carried out. It confirmed the findings of similar studies in that mesothelioma occurs predominantly in those exposed by reason of their occupation. No relationship with place of residence was apparent independent of occupation. PMID- 2325393 TI - Interracial friendship in a Zimbabwean primary school. PMID- 2325394 TI - Type A behavior and self-reported stress among Zimbabwean teachers. PMID- 2325395 TI - Academic achievement of children from monogamous and polygynous families. PMID- 2325396 TI - Obesity as a self-handicapping strategy: personality, selective attribution of problems, and weight loss. PMID- 2325397 TI - Factors affecting attitudes toward persons with AIDS. PMID- 2325398 TI - Re-examining the link between job characteristics and job satisfaction. PMID- 2325399 TI - Children's understanding of the mitigating function of disclaimers. AB - Despite earlier work indicating young children's competence in the use and understanding of retrospective "facework strategies" such as apologies, justifications, and excuses, it was hypothesized that an understanding of the disclaimer, a prospective strategy, would be relatively late appearing. An experiment is reported in which 144 British children between the ages of 5 and 11 years were presented with stories concerning an actor who had brought about certain negative consequences, having either previously issued, or not, a disclaimer. Children were asked to indicate and justify whether they felt the actor should be punished. Broadly consistent with the hypothesis guiding the present study, significant reductions in punishment recommendations following the provision of a disclaimer were found only among the 11-year-old subjects. However, from subjects' justifications for the decision not to punish, it was noted that nearly 50% of the 8-year-olds and 25% of the 5-year-olds provided evidence of understanding the mitigating function of disclaimers. PMID- 2325400 TI - Lunar phases and crisis center telephone calls. AB - The lunar hypothesis, that is, the notion that lunar phases can directly affect human behavior, was tested by time-series analysis of 4,575 crisis center telephone calls (all calls recorded for a 6-month interval). As expected, the lunar hypothesis was not supported. The 28-day lunar cycle accounted for less than 1% of the variance of the frequency of crisis center calls. Also, as hypothesized from an attribution theory framework, crisis center workers reported significantly greater belief in lunar effects than a non-crisis-center-worker comparison group. PMID- 2325401 TI - Religious motivation in the elderly: a French-Canadian replication and an extension. AB - To clarify further the relationship between religiosity and personal adjustment, four kinds of religious motivation were distinguished: intrinsic, self-determined extrinsic, non-self-determined extrinsic, and amotivation. A study of 176 French Canadian elderly people found that these four kinds of religious motivation can be reliably measured, that they display a pattern of intercorrelations consistent with theoretical predictions, and that they are related to other important aspects of the lives of these elderly people in a theoretically meaningful manner. PMID- 2325402 TI - Upward mobility, status inconsistency, and psychological health. AB - According to much of the theoretical literature, the psychological consequences of intergenerational occupational mobility are associated with poorer psychological health, even when upward mobility is involved. One possible explanation is that mobility results in status inconsistencies that are experienced as stressful. The research reported here reconsiders the notions that mobility is associated with higher levels of stress and that stress results from exposure to status inconsistencies. The results obtained, based on a sample of English men, provide no support for either thesis. PMID- 2325403 TI - Authoritarianism and attitudes toward AIDS victims. AB - This study investigated the relationship of authoritarianism and attitudes toward AIDS victims in three samples. One hundred fifty-eight students at Oregon State University participated, including 101 students from the United States, 25 from Japan, and 32 from other Asian societies. The survey instrument included the 20 item Attitudes Toward AIDS Victims (ATAV) Scale, the 18-item F Scale, the Form A, and 14-item Formal Content of Dogmatism Scale. Results showed slight but significant correlations between the ATAV and F (r = .17, p less than .044) and Formal Content of Dogmatism (r = .20, p less than .023) Scales for the United States sample. Highly significant differences were found in the predicted direction among the three samples on authoritarianism, F = 43.94, p less than .001. PMID- 2325404 TI - Decision making of satisfied and dissatisfied married couples. AB - Ten satisfied and ten dissatisfied married couples described how they make decisions of low, moderate, and high levels of difficulty. Responses were coded as reflecting the use of equity, need-based, situational, or other norms. Results were consistent with previous findings that a state of equity is associated with marital satisfaction but also indicated that multiple norms are used in decision making of both satisfied and dissatisfied couples. Decision difficulty influenced use of both situational and need-based norms. A trend was found for satisfied husbands but not wives, to make greater use of need-based norms than dissatisfied husbands when decisions were high in difficulty. The results are interpreted as supporting a distinction between equity as a state and equity as a process and as supporting an instrumental value theory of norm use. PMID- 2325405 TI - Radioimmunoassay of the anti-cancer agent 4-hydroxyandrostenedione in body fluids. AB - Antibodies were produced in sheep against a new anti-breast cancer drug 4 hydroxyandrostenedione (4-OHA) using two hapten-ovalbumin conjugates. One of these conjugates (4-hydroxytestosterone-ovalbumin) produced an antiserum suitable for the development of a radioimmunoassay that would allow direct measurement of 4-OHA in plasma at concentrations down to 82 pmol/l, with adequate accuracy, precision and scope for further sensitivity. Although this assay would measure 4 hydroxytestosterone (4-OHT) in addition to 4-OHA, the present data suggest that the magnitude of any interference from endogenous steroids and those derived from 4-OHA could only be minimal. A comparison of solvent-extracted and unextracted samples showed that only unconjugated drug was analysed by this radioimmunoassay. A study of plasma protein binding of 4-OHA showed that at therapeutic concentrations, between 13.5 and 16.5% of plasma 4-OHA was not bound to proteins. This assay system could be a useful adjunct to the future development of 4-OHA as an anti-cancer drug. PMID- 2325407 TI - The binding properties of pyrethroids to human skin fibroblast androgen receptors and to sex hormone binding globulin. AB - The pyrethroids are a class of natural and synthetic pesticides which were associated with an epidemic of gynecomastia in Haitian men in 1981. In the present study we tested several pyrethroids for their ability to interact with androgen binding sites in dispersed, intact human genital skin fibroblasts and in human plasma to sex hormone binding globulin (SHBG). All the pyrethroids tested inhibited fibroblast binding of [3H]methyltrienolone (R1881) at 22 degrees C with the following rank order of potency:pyrethrins greater than bioallethrin greater than fenvalerate greater than fenothrin greater than fluvalinate greater than permethrin greater than resmethrin. 50% displacement of [3H]R1881 binding to fibroblast androgen receptors was achieved by 1.5-44 x 10(-5) M concentrations of the competitors, respectively. Previous studies with cimetidine, a known inhibitor of androgen receptor binding, showed 50% competition at a concentration of 1.4 x 10(-4) M in this system. Scatchard analysis of binding experiments performed with increasing concentrations of [3H]R1881 in the presence of the pyrethroids indicated that the binding inhibition was competitive. On the other hand, of the pyrethroids examined only the pyrethrins (50% inhibition) and bioallethrin (43% inhibition) were able to displace [3H]testosterone from SHBG when tested at a concentration of 10(-4) M. These data indicate that a novel class of non-steroidal compounds, the pyrethroids, can interact competitively with human androgen receptors and SHBG. These findings provide a mechanism by which chronic exposure of humans or animals to pesticides containing these compounds may result in disturbances in endocrine effects relating to androgen action. PMID- 2325406 TI - The binding of 3H-labelled androgen-receptor complexes to hypothalamic chromatin of neonatal mice: effect of sex and androgenization. AB - The binding of 3H-labelled androgen-receptor complexes, prepared by (NH4)2SO4 precipitation from the 105,000 g supernatant of hypothalamic cytosol, to hypothalamic chromatin of neonatal mice covalently coupled to cellulose was measured in vitro. Saturation binding was also determined after extraction of histones and the masking of acidic proteins with high molarities of guanidine hydrochloride. This investigation showed the presence of high-affinity, low capacity acceptor sites for [3H]-testosterone-receptor complexes in male hypothalamic chromatin (Kd value = 0.39 x 10(-10) M and binding sites of 41 fmol per mg of DNA). Acceptor activity seems to be associated with the acidic protein fraction of chromatin. No specific acceptor sites of similar nature were found in chromatin taken from the hypothalami of female mice. On the basis of these results, it is suggested that the androgen-unresponsiveness of female mice is related to the absence of acceptors for the androgen-receptor in female mice hypothalami. PMID- 2325408 TI - A comparative study of the interaction of oestradiol and the steroidal pure antioestrogen, ICI 164,384, with the molybdate-stabilized oestrogen receptor. AB - The kinetics of binding of oestradiol and the steroidal pure antioestrogen ICI 164,384 to the molybdate-stabilized oestrogen receptor, partially purified from pig and human uterine tissue, were determined. ICI 164,384 bound directly to the oestrogen receptor protein and the kinetic parameters of this interaction were, in general, similar to those for the binding of oestradiol, regardless of the source of the receptor protein. However, the rate of association of oestradiol, regardless of the source of the receptor protein. However, the rate of association of the antagonist with the receptor protein was slower when compared to that of oestradiol. Furthermore, the concentration of binding sites for the two ligands was of the same order. The binding of oestradiol resulted in a steroid-receptor complex which could be transformed in vitro, to a form with increased affinity for DNA-cellulose. However, the complex formed between ICI 164,384 and the receptor protein did not show increased affinity for DNA cellulose when exposed to conditions that transformed agonist-receptor complexes. Therefore, the binding of ICI 164,384 to the oestrogen receptor protein results in a suppression of the transformation process. A similar suppression in vivo may account for the pure antagonist properties of ICI 164,384. PMID- 2325409 TI - Pronounced and differential effects of ionic strength and pH on testosterone oxidation by membrane-bound and purified forms of rat liver microsomal cytochrome P-450. AB - The aim of this study was to determine the effects of ionic strength and pH on the different pathways of testosterone oxidation catalyzed by rat liver microsomes. The catalytic activity of cytochromes P-450a (IIA1), P-450b (IIB1), P 450h (IIC11) and P-450p (IIIA1) was measured in liver microsomes from mature male rats and phenobarbital-treated rats as testosterone 7 alpha-, 16 beta-, 2 alpha- and 6 beta-hydroxylase activity, respectively. An increase in the concentration of potassium phosphate (from 25 to 250 mM) caused a marked decrease in the catalytic activity of cytochromes P-450a (to 8%), P-450b (to 22%) and P-450h (to 23%), but caused a pronounced increase in the catalytic activity of cytochrome P 450p (up to 4.2-fold). These effects were attributed to changes in ionic strength, because similar but less pronounced effects were observed with Tris-HCl (which has approximately 1/3 the ionic strength of phosphate buffer at pH 7.4). Testosterone oxidation by microsomal cytochromes P-450a, P-450b, P-450h and P 450p was also differentially affected by pH (over the range 6.8-8.0). The pH optima ranged from 7.1 (for P-450a and P-450h) to 8.0 (for P-450p), with an intermediate value of 7.4 for cytochrome P-450b. Increasing the pH from 6.8 to 8.0 unexpectedly altered the relative amounts of the 3 major metabolites produced by cytochrome P-450h. The decline in testosterone oxidation by cytochromes P 450a, P-450b and P-450h that accompanied an increase in ionic strength or pH could be duplicated in reconstitution systems containing purified P-450a, P-450b or P-450h, equimolar amounts of NADPH-cytochrome P-450 reductase and optimal amounts of dilauroylphosphatidylcholine. This result indicated that the decline in testosterone oxidation by cytochromes P-450a, P-450b and P-450h was a direct effect of ionic strength and pH on these enzymes, rather than a secondary effect related to the increase in testosterone oxidation by cytochrome P-450p. Similar studies with purified cytochrome P-450p were complicated by the atypical conditions needed to reconstitute this enzyme. However, studies on the conversion of digitoxin to digitoxigenin bisdigitoxoside by liver microsomes, which is catalyzed specifically by cytochrome P-450p, provided indirect evidence that the increase in catalytic activity of cytochrome P-450p was also a direct effect of ionic strength and pH on this enzyme.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2325410 TI - Modulation of quail oviduct adenylate cyclase activity by estradiol and progesterone. AB - Oviduct adenylate cyclase activity of the quail was measured by radiochemical analysis following different hormonal treatments. A single injection of estradiol benzoate (EB) to immature female quails resulted in a prereplicative surge of adenylate cyclase activity. A second surge of enzyme activity was observed during the proliferative phase induced by EB. Estradiol-17 alpha, estrone, estriol and testosterone were ineffective. Tamoxifen completely inhibits the growth-promoting effect of EB and the second surge of adenylate cyclase activity but does not inhibit the prereplicative increase of enzyme activity. This prereplicative increase of adenylate cyclase activity was also observed, even in the absence of increased plasma estradiol, when estradiol-17 beta (E2) was perfused through the hepatic portal vein. Moreover, E2 had no effect on enzyme activity when added directly to the oviduct homogenate preparation, at concentrations ranging from 10(-9) to 10(-7) M. In response to progesterone injection, oviduct adenylate cyclase activity followed a different pattern, beginning its increase after 3 h and remaining elevated up to 24 h. The activation by estradiol was independent of the presence of guanylylimidodiphosphate. Moreover, the enzyme was more sensitive to forskolin at submaximal concentration in estradiol treated birds than in control. These results demonstrate that transient activation of adenylate cyclase at the early stages of the action of estradiol does not occur through the classic nuclear receptor-gene activation pathway or a membrane receptor mediated process, but involves an indirect pathway, yet to be defined. PMID- 2325411 TI - A new method of detecting hormone-binding proteins electroblotted onto glass fiber filter: juvenile hormone-binding proteins from grasshopper hemolymph. AB - We have developed a new method to identify juvenile hormone (JH)-binding proteins blotted onto glass fiber filter (GFF) after electrophoretic separation. Insect JH regulates reproduction in the two-striped grasshopper, Melanoplus bivittatus. A number of proteins are involved in the delivery of JH from its site of synthesis to the nuclei of fat body cells where it acts to induce vitellogenesis. To identify JH binding proteins, hemolymph was separated by PAGE, electroblotted onto GFF, and incubated in [10-3H]JH-III. The amount of hormone bound by blotted proteins increased with the amount of protein on the filter, was competitively displaced by excess non-labeled hormone, and was affiliated with individual bands on fluorograms of proteins blotted after electrophoretic separation. GFF etched with trifluoroacetic acid was better than nitrocellulose, Zeta Probe, cellulose acetate or unetched GFF. Phosphate (pH 6.0-7.3) or Tris buffers (pH 7.3-8.0) worked equally well for the procedure. Unbound hormone was easily removed by short washes in buffer, and adequate binding for detection was achieved in a 15 min incubation. Preliminary data suggest that this technique may be used to detect receptors, carriers, and binding proteins of steroid hormones. PMID- 2325412 TI - In vivo and in vitro estimations of the direct effect of estrogen on rat hepatocytes tested by the changes in the unusual estrogen-binding protein content. AB - The direct effect of estradiol (E2) on the hepatocytes of mature male rats has been examined by measuring the changes in the unusual estrogen-binding protein (UEBP) content and parallel measuring the level of liver estrogen receptors (ER). The content of UEBP (NUEBP) and ER (NER) in the liver were determined using the quantitative methods for differential specific determination of the E2-binding sites of these proteins. It has been shown that the administration of E2 in vivo induced a considerable decrease in hepatic NUEBP not only in intact males, but also in hypophysectomized males during the initial period after the operation (when the content of hepatic ER was still high) and produced no effect in hypophysectomized males during the later period (when liver ER were depleted). Repeated administration of human growth hormone (hGH) (twice a day) resulted in a considerable increase in NER in hypophysectomized males and restored the sensitivity to the subsequent inhibitory effect of E2 on UEBP. We also used rat hepatocytes after a 4-day primary culturing. These cells had a stable morpho functional status, high ER level, and sex-differentiated UEBP content. Culturing of mature male rat hepatocytes in the medium containing E2 at concentrations close to physiological levels (10(-10)-10(-7) M) decreased NUEBP in a dose dependent manner. Hexestrol (10(-7) M) but not cholesterol (10(-5) M) also exhibited a direct effect on NUEBP in cultured rat hepatocytes. The effect of E2 was reversible: statistically significant increase in NUEBP was observed 3 days after 10(-9) M E2 had been removed from the culturing medium. It was concluded that hepatocytes may be a primary target for E2 under physiological conditions and that GH may modulate the direct effect of E2 at the hepatic level by modifying the content of liver ER. PMID- 2325413 TI - Structure-activity relationships in the in vitro modulation of rat hepatic microsomal androst-4-ene-3,17-dione hydroxylase activities by derivatives of 5 alpha- and 5 beta-androstane. AB - The relationships between structure and inhibitory potency toward microsomal cytochrome P-450 (P-450)-mediated androst-4-ene-3,17-dione hydroxylase activities were investigated in rat liver with a series of 5 alpha- and 5 beta-androstane derivatives. 5 beta-Reduced steroids (containing a cis-A/B ring junction) were more potent inhibitors than the 5 alpha-reduced epimers (containing a trans-A/B ring junction) except in the case of the 17 beta-hydroxy-substituted derivatives. The most effective inhibitor was 5 beta-androstane-3 beta-ol which exhibited I50 values of 7 and 27 microM against androstenedione 16 alpha- and 6 beta hydroxylase activities, which are catalysed by P-450 IIC11 and IIIA2, respectively. In general, these two pathways of steroid hydroxylation were more susceptible to inhibition than the 7 alpha- and 16 beta-hydroxylase pathways. The 7 alpha-hydroxylase enzyme (P-450 IIA1) was only inhibited by 5 beta-reduced steroids that contained an oxygenated function at C17. All of the test compounds elicited type I spectral binding interactions with P-450 in oxidised microsomes. The most effective steroid inhibitors generally exhibited the greatest capacity to interact with P-450. Additional studies with one of the more potent compounds, 5 beta-androstane-3 beta-ol-17-one, revealed that the inhibition kinetics were competitive and that preincubation of the inhibitor with NADPH-supplemented microsomes prior to substrate (androstenedione) addition decreased the extent of inhibition observed. These findings are consistent with the assertion that the inhibition of hepatic steroid hydroxylases by 5 beta-androstanes involves an effective competitive interaction with the steroid substrate at the P-450 active site. Since the relative overproduction of 5 beta-reduced metabolites of certain androgens has been reported in clinical conditions, such as androgen insensitivity, it now appears important to investigate the hepatic drug oxidation capacity of patients with hormonal abnormalities. PMID- 2325414 TI - Progesterone treatment suppresses estrogen receptor in the sex skin of Macaca nemestrina. AB - We measured tightly bound nuclear estrogen receptors (ER) in sex skin biopsies obtained from pig-tailed macaques (Macaca nemestrina) which were previously ovariectomized and treated with an estradiol-progesterone regimen. Incubation of fresh tissue slices with a saturating concentration of [3H]estradiol (E2) was done to determine the capacity of nuclear acceptor sites to bind activated ER with high affinity. The radiolabeled ER was extracted from nuclei with 0.5 M KCl, complexed with an anti-ER monoclonal antibody, and quantitated by analysis on sucrose gradients. Even though serum E2 levels were unchanged, 7 and 14 days of sequential progesterone (P) treatment decreased ER amounts below those found after 7, 14 and 21-23 days of E2 treatment. ER regulation in sex skin of this species is similar to that found in macaque reproductive tract; P suppresses ER levels even in the presence of continuous E2. The tissue responses of sex skin to the hormone treatments correlated well with the measured fluctuations of tightly bound nuclear ER, which suggests the functional significance of this ER component. PMID- 2325416 TI - The binding of cortisol to adrenal mitochondria. AB - Binding of tritiated cortisol to adrenal zona glomerulosa mitochondria was studied and compared with that of corticosterone. Cortisol was shown to bind specifically to the inner membrane of zona glomerulosa mitochondria. Corticosterone and cortisol had similar apparent association constants (Ka) and concentrations of binding sites. The methodology was validated by obtaining similar Ka from both binding plots and kinetic data. Cortisol binding was inhibited by pretreatment with sodium dithionite, and displaced by deoxycorticosterone, corticosterone, 18-hydroxy-corticosterone, 11 beta-hydroxy 18-ethynyl-progesterone and metyrapone, but not by cholesterol. These results suggest that cortisol and corticosterone bind to the same cytochrome P-450. PMID- 2325415 TI - Pregnenolone binding sites in the rat olfactory bulb. AB - High concentrations of pregnenolone and its sulfate have been found in several areas of rat and human brain and seem to be controlled by local mechanisms. In the present experiments we have demonstrated pregnenolone binding sites in the cytosolic fraction of the rat olfactory bulb. The pregnenolone binding component showed a Kd = 2.34 +/- 0.66 x 10(-7) M and Nmax = 7.25 +/- 1.20 pmol/mg protein. Pregnenolone, pregnenolone sulfate and 17OH-pregnenolone competed equally for the binding sites while other steroids were less competitive. Protease and trypsin inhibited binding by 48 and 60% respectively. Sucrose density gradient analysis showed a minor peak at 4.6 s and a major one at 3.6 s. After gel filtration chromatography the pregnenolone binding component appeared as 2 peaks corresponding to molecular weights of approximately 150 and 220 kDa. Heating at 60 degrees C increased binding by 150%. These results indicate that the olfactory bulb pregnenolone binding component is complex in nature. Rat plasma also bound pregnenolone. Plasma binding sites could be partially differentiated from those in the olfactory bulb on the basis of susceptibility to lipoprotein lipase, effect of heating and mobility during polyacrylamide gel electrophoresis. PMID- 2325417 TI - Are we positive about node negative breast cancer? PMID- 2325418 TI - Impact of the time interval between surgery and postoperative radiation therapy on locoregional control in advanced head and neck cancer. AB - Between January 1975 and December 1980, 111 patients with AJCC stages III and IV squamous cell carcinoma of the head and neck were treated with surgery followed by planned postoperative radiation therapy. A previous analysis of a subgroup of these patients showed that, when radiation was delayed more than 6 weeks from surgery, a higher incidence of regional failure occurred compared with the incidence observed when therapy began within a 6 week period. We have looked back at this group of patients plus others in an attempt to determine whether other factors played a role in the results obtained. In the current study, 50 patients had a delay of 6 weeks or more and, of these, 11 (22%) suffered a locoregional recurrence. However, 8 of these 11 patients received suboptimal radiation doses (less than 56 Gy) for permanent control of the disease. In fact, of 17 patients who received at least 60 Gy and had more than a 6 week delay, only 2 (12%) had locoregional failure. This was similar to the incidence of failure in the patients who received at least 60 Gy and who started radiation within the first 6 weeks from surgery (3/20 [15%]). The effect of delay was apparent only in those who received less than 60 Gy (27% vs. 7%, P less than 0.05). Therefore, we cannot validate the previous conclusion that a greater than 6 week delay in the delivery of postoperative radiation therapy in advanced head and neck cancers produces poorer results. The current analysis suggests that a prolonged delay in postoperative radiation therapy in itself does not have a negative impact on locoregional control as long as appropriate tumorcidal doses of more than 60 Gy are employed. PMID- 2325420 TI - Role of brachytherapy in malignant melanoma: a preliminary report. AB - From August 1979 to May 1986, various brachytherapy techniques were applied at Memorial Sloan Kettering Cancer Center (MSKCC) in an adjuvant setting with/without surgery and external radiation therapy in the management of advanced malignant melanoma. Thirty-three patients underwent brachytherapy procedures. The patients' ages ranged from 35 to 82 years, with a median age of 56 years. Fourteen patients had disease localized to the implant site, whereas 19 patients also had disseminated disease elsewhere. The indications for implant were residual gross disease (21), microscopically positive margins (3), and histologically negative but clinically close margins of resection (9). Local control at the implant site was noted in 80% of patients at 6 months and 42% of patients at 1 year; two patients had reached 54 months and 72 months with no evidence of disease. Local control was 100% (9/9) in patients with histologically negative but clinically close margins of resection, and 48% (11/23) with microscopically positive margins and/or gross residual disease. Complications were seen as follows: delay in wound healing (1), wound infections (4), radiation enteritis (1), small bowel obstruction (1). The present study suggests that brachytherapy combined with surgery can achieve a good local control in patients with negative but clinically close margins of resection. In patients with gross residual disease who are at a high risk for local recurrence, approximately one half can be locally controlled with this approach. These preliminary results should be tested in a prospective controlled study. PMID- 2325419 TI - Prognostic significance of laminin in adenocarcinoma of the lung. AB - The distribution of laminin in tumor-associated basement membrane was immunohistochemically investigated in 115 cases of adenocarcinoma of the lung. The distribution of laminin was classified into continuous and discontinuous staining patterns. The incidence of the discontinuous pattern was less in early stage disease than that in advanced stages (P less than 0.01). In patients with stage I, the incidence of discontinuous patterns was greater in short-term survivors than in long-term survivors (P less than 0.05). By contrast, in patients with stage III, the discontinuous pattern of laminin was frequently seen in both long-term survivors and short-term survivors, with no difference between the two groups. These data suggest that the discontinuous pattern of laminin in tumor-associated basement membrane reflects the spread and dissemination of tumor, hence a close relationship to the prognosis. PMID- 2325421 TI - Bloody nipple discharge during pregnancy: a rationale for conservative treatment. AB - Five cases of bloody nipple discharge during pregnancy without associated breast masses were seen over the past 3 years by the author. Because of the reported association of breast cancer with bloody nipple discharge, close follow-up of these women at monthly intervals during pregnancy and trimonthly during the postpartum period was carried out. In all instances, the discharge appeared late during the second trimester or during the third trimester of pregnancy. It was unilateral and spontaneous and arose from multiple ducts, and it was associated with an increase in breast size and always with the larger breast of the two. The discharge cytologic study done on all cases was negative for neoplastic cells and the discharges resolved spontaneously within 2 months of onset. Postpartum follow up ranging from 6 months to 3 years has revealed no evidence of neoplastic changes thus far. Mammograms ordered before these patients were referred were not helpful due to the increase in density of the breast tissue secondary to the pregnancy. Because a few cases of breast cancer during pregnancy have presented solely with a bloody nipple discharge, I recommend extremely close follow-up of these women and no surgical intervention unless a mass is discovered or the nipple discharge cytology is either suspicious or positive at the initial visit or during follow-up. PMID- 2325422 TI - Intraarterial infusion chemotherapy in regionally advanced malignant melanoma. AB - The therapeutic effectiveness of intraarterial cisplatin (CDDP) and dacarbazine (DTIC) infusion was examined in 30 evaluable patients with regionally advanced melanoma that was refractory to standard treatments. Objective responses were achieved in 11 patients (37%), including three complete (10%) and eight partial (27%) tumor regressions. Successful debulking surgery was performed in seven of the eleven patients with response. Six remained free of regional disease after a median time of 25 months, and four are also free of distant metastases at 24+, 25+, 41+, and 54+ months. Nineteen of thirty patients with no significant tumor response underwent alternative treatments. Debulking surgery was performed in nine, but with little palliative gain, since seven relapsed at a median time of 5 months. Our results suggest that a combined therapeutic approach--preoperative chemotherapy followed by surgery in responding tumors--represents an effective treatment for patients with regionally advanced melanoma. PMID- 2325423 TI - Complications following surgery for cancer of the larynx and pyriform fossa. AB - The hospital records of patients undergoing major surgery for cancer of the larynx and hypopharynx at the Tata Memorial Hospital, Bombay, from 1981 to 1985 were reviewed. Different variables were correlated with the incidence of major complications and were analysed to find out significant factors contributing to increased complication rates. Complications included wound infection, pharyngocutaneous fistulae, flap necrosis, carotid blowout, and neo-esophageal stenosis. Postoperative deaths and delayed fatalities were also recorded. The overall fistulae rate was 34.7%, and wound infection occurred in 28% of patients. Prior radiotherapy and the need for pharyngeal reconstruction were found to be significant in determining postsurgical complications. Age, sex, site, stage, cartilage and soft tissue infiltration, preoperative tracheostomy, involvement of resection margins by tumor, and the dose of radiotherapy were not found to influence the complication rates. PMID- 2325424 TI - Benign schwannoma and parathyroid adenoma occurring in the nonradiated neck: report of two cases. AB - The late occurrence of multiple neoplasms in the previously radiated neck is a well-known association. However, multiple tumours in the nonradiated neck remain a rare finding. This paper presents two cases of the infrequently seen schwannoma occurring with a parathyroid adenoma without antecedent history of radiation or neurofibromatosis. PMID- 2325425 TI - Nursing scholarship program. PMID- 2325427 TI - Organized nursing makes strides to ease nursing shortage. PMID- 2325426 TI - Nursing's new directions. PMID- 2325428 TI - Macrophages but not B cells from aged mice are defective in stimulating autoreactive T cells in vitro. AB - In the present study the effect of aging on the capacity of Ia+ cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4+ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherent cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia+ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-1 could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4+ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells and in stimulator splenic macrophages but not in the stimulatory activity of B cells. PMID- 2325429 TI - The effect of taurine on age-related immune decline in mice: the effect of taurine on T cell and B cell proliferative response under costimulation with ionomycin and phorbol myristate acetate. AB - Proliferative responses to the costimulation with phorbol-12-myristate-13-acetate (PMA) and suboptimal doses of ionomycin in the purified T and B cells from old mice were lower than those from young mice. The degree of the age-related decline was more significant in T cells than in B cells. Taurine, a sulfur containing amino acid, augmented the proliferative responses of T cells from both young and old mice. The augmentation of the proliferative response by taurine was more marked in old T cells than in young ones. The concentration of intracellular free calcium ion ([Ca2+]i) was significantly lower in the old T cells under the stimulation with PMA and ionomycin than that in the young ones. In the presence of taurine, the concentration of [Ca2+]i in the old T cell significantly increased under the stimulation. The results indicate that taurine improved the proliferative response of old T cells by the restoration of the increment of the concentration of [Ca2+]i under the stimulation. PMID- 2325430 TI - Blood-brain transport of triiodothyronine is reduced in aged rats. AB - An age-related decline in blood-brain barrier transport of thyroid hormones may contribute to the central nervous system changes with aging. To test this hypothesis, the brain uptake index (BUI) of levo (L) and dextro (D) triiodothyronine (T3) was determined in male Fischer 344 rats at 6 months of age (young) and 26 months of age (aged). Young rats pair fed with aged were included to control for reduced food intake in aged rats. The L-T3 BUI of aged rats (22.4 +/- 2.1%) was significantly reduced compared to young rats (29.5 +/- 2.0%) or young rats pair fed with aged rats (28.5 +/- 2.5%) (p less than 0.05). This could not be attributed to age-related changes in BBB permeability or to reduced cerebral blood flow. At steady state conditions, the brain uptake of either L-T3 or D-T3 was not altered with aging. There were no significant changes in plasma or brain binding of T3. These results indicate that the reduced BBB transport of T3 in aged rats is counterbalanced by a reduction in T3 clearance from the brain. PMID- 2325431 TI - A new method for testing cell ageing using two mitochondria specific fluorescent probes. AB - Cell culture techniques have considerably improved our understanding of the numerous changes related to aging. For instance, murine lymphocytes obtained from animals older than 6 months progressively lose their, in vitro, proliferative capacity. Numerous studies have shown that this loss is due to changes in the mitochondrial compartment such as reduction in the transmembrane potential and/or membrane mass. Using two mitochondria specific probes with a potential-dependent (Rhodamine 123) or independent (Nonyl Acridine Orange) uptake, we found that the decline in the respiratory activity in the mouse occurred approximately 6 months prior to the decrease in mitochondrial membrane mass. The analysis of the Rh 123/NAO fluorescence ratio measured in splenocytes obtained from mice aged more than 6 months, showed that there was a linear loss of respiratory efficiency per unit of mitochondrial membrane mass. Moreover, cells with a ratio of less than 0.85 were incapable of proliferating and remained quiescent. The time separating the infection points of the two dye uptake curves might provide informations about the regulation and coordination of nuclear and/or mitochondrial genomes. Moreover, the ratio between the two fluorescent probes, in particular during the linear phase, may also have a predictive value. PMID- 2325432 TI - Forskolin activation of adenylate cyclase in rat myocardium with age: effects of guanine nucleotide analogs. AB - Beta-adrenergic and post-receptor activation of adenylate cyclase decreases with age in the rat myocardium. Forskolin-stimulated adenylate cyclase activity decreases with age to the same extent as NaF or isoproterenol stimulation, suggesting that a loss of catalytic unit activity accounts for the loss of activity with age. However, recent evidence suggests that there are both a guanine nucleotide-dependent and independent component of forskolin activation. We assessed the possible role of each of these components with age by measuring forskolin dose-response stimulation of adenylate cyclase activity in the presence and absence of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta S) and beta,gamma imidoguanine 5'-triphosphate (Gpp(NH)p) in myocardial membranes from F-344 rats of 3, 12, and 24 months of age. Maximal forskolin stimulation of adenylate cyclase was least in the 24- (121 +/- 21 pmol cAMP/min/mg) as compared with either the 12- (212 +/- 29) or 3- (190 +/- 19) month-old rats. The presence of GDP-beta S had no effect on either the EC50 or maximum activity, and the age related decline persisted. Gpp(NH)p plus isoproterenol enhanced forskolin activation but the effect was additive and not synergistic. There was no effect on the EC50, and the maximum activity was least in the 24-month-old rats. These data reconfirm the loss of catalytic unit activity with age and indicate that the reduced activity with age is independent of the presence or absence of activated G-protein. PMID- 2325433 TI - Adrenergic innervation of the tibial and vagus nerves in rats of different ages. AB - Adrenergic nerve fibers innervating blood vessels in the epi-perineurium and endoneurium of the tibial and vagus nerves of male Fischer-344 rats of different ages were examined using formaldehyde-induced fluorescence technique and fluorescence microscopy. Between 6 and 24 months of age, no significant difference in the mean density of perivascular innervation in the epi-perineurium of the nerves was found, whereas between 24 months and 30 months the density decreased in both nerve types. The intensity of noradrenaline fluorescence of nerve fibers also was decreased in the oldest age group. In the endoneurium, the density of adrenergic nerve fibers was reduced by 57% at 24 months, and by more than 98% at 30 months as compared with 18 months. Age-related differences were similar in the tibial and vagus nerves. The results suggest that adrenergic neuronal control of the microcirculation in the rat tibial and vagus nerves is lost during aging as it is in other organs of the cardiovascular system. PMID- 2325434 TI - Monoclonal gammopathies in human aging: increased occurrence with age and correlation with health status. AB - To determine the incidence of monoclonal gammopathies (MG) in relation to the aging process as such, and to evaluate the influence of disease on the occurrence of MG, we studied 439 elderly subjects aged 75-84 years. These individuals were categorized into 4 groups on the basis of their health status. There was a group of "optimally healthy" elderly, a group of "apparently healthy" residents of homes for the aged, a group of geriatric outpatients and a group of randomly chosen inpatients from a general hospital. Whereas no MG were detected in a control group of healthy young subjects aged 25-34 years, the frequency of MG in the aged groups ranged from 11% in the "optimally healthy" aged group to 38% in the inpatients group. In a tentative classification according to possible cause, most of the MG belonged to the pathogenetic category of immunodeficiency. There was a clear association of the occurrence of monoclonal gammopathies of this category with the health status. PMID- 2325435 TI - Improvement of natural killer cell activity by in vitro active lipids (AL 721) administration in old mice. AB - Results of several experiments have given rise to the hypothesis that the decline of the immunocompetence with aging is at least in part related to alterations of the lipid membrane composition and, consequently, to a decrease in membrane fluidity. The age-dependent decline of mitogen responsiveness can, in fact, be reversed by a special lipid mixture designated as active lipids (AL 721), which acts by means of its fluidizing action on the plasma membrane. The purpose of this study was to examine the possibility of raising the low endogenous levels of Natural Killer (NK) activity by in vitro AL administration in old mice. When spleen cells from old mice were incubated in vitro with AL, a significant increase in cytotoxic activity was obtained over control cultures, without reaching, however, the levels observed in young mice. In spleen cells from young mice, the AL administration causes a slight augment of NK basal activity. These results suggest that cell membrane fluidity plays an important role in the efficiency of NK cells, giving support to the hypothesis that a rectification of rigidified cell membranes may represent a valuable approach to restore proper physiological functions in old age. PMID- 2325436 TI - The red blood cell glutathione reductase activity in anaemic rats. AB - The enzyme activity of glutathione reductase (GR, EC 1.6.4.2) was measured in rat red blood cells separated centrifugally in a density gradient of Percoll. The animals were divided into three groups: Groups IPHH, anaemia was induced by administration of phenylhydrazine hydrochloride; Group IITr, anaemia was induced by intense physical training; and Group C, control group. The activity of active and inactive forms of GR were higher in erythrocytes of animals from groups IPHH and IITr, both in young and old forms of cells, than in red cells of control rats, the degree of decrease in activity of both forms of GR in senescent red cells is similar in different kinds of anaemia. PMID- 2325438 TI - Effect of age on intestinal regeneration in the rabbit. AB - We compared the rate of regeneration of full thickness serosa patched intestinal defects to determine whether this regenerative process is influenced by age. Twenty-five rabbits aged 3, 9, 15, 36 and 60 months were killed 3 weeks after patching. Epithelialization was slightly but significantly greater in the 3-month old rabbits but there were no differences in contraction of the patched defect or villus development of the regenerating mucosa. Disaccharidase activity was greatest in the older animals but glucose uptake was similar at all ages. Proliferative activity was similar as well. Thus, intestinal regeneration in full thickness intestinal defects does not appear to be influenced significantly by the age of the animals. PMID- 2325437 TI - Changes in metabolite transport by small intestine and kidney of young and old rats. AB - We have studied the influence of the ageing phenomenon on metabolite absorption by the small intestine and the kidney of the rat, using isolated brush-border membrane vesicles prepared from 2 groups, one composed of 2 month, and the other of 24 month, animals. "Overshoot", which is typical of Na(+)-glucose cotransporter activity, disappeared in the duodenum and decreased in the kidney of the old rats. Short-circuiting of vesicles with valinomycin showed that, in the presence of K+ and valinomycin, "overshoot" decreased in both groups by about the same percentage. The Na(+)-dependent uptake of aspartate and phenylalanine showed contrasting pictures in the jejunum and kidney of the aged animals: aspartate transport decreased only in the kidney, while phenylalanine uptake was negatively affected in the jejunum. Na(+)-dependent citrate uptake, studied in renal brush-border membrane vesicles, was lower in the old rats. The Km values determined for Na(+)-dependent D-glucose and citrate uptake in the kidney did not meaningfully differ between the two groups. A continuous decrease in Na(+) dependent D-glucose and citrate uptake in the rat kidney, during ageing, was demonstrated. PMID- 2325439 TI - Changes in boron concentration during development and ageing of Drosophila and effect of dietary boron on life span. AB - Total boron concentrations in Drosophila changed during development and ageing. The highest concentration of boron was found during the egg stage followed by a decline during the larval stages. Newly emerged flies contained 35.5 ppm boron. During the adult stage the boron concentration increased by 52% by 9 weeks of age. Adding excess dietary boron during the adult stage decreased the median life span by 69% at 0.01 M sodium borate and by 21% at 0.001 M sodium borate. Lower concentrations gave small but significant increases in life span. Supplementing a very low boron diet with 0.00025 M sodium borate improved life span by 9.5%. The boron contents of young and old mouse tissues were similar to those of Drosophila and human samples. We conclude that moderate levels of dietary boron may have a general protective effect in biological systems. The mechanism of this effect at present remains unknown. PMID- 2325440 TI - Effect of age on the expression of antioxidant enzymes in male Fischer F344 rats. AB - Age-related changes in the activities of superoxide dismutase, catalase, and glutathione peroxidase were determined in brain, heart, hepatocytes, intestinal mucosa, and kidney from male Fischer F344 rats. Superoxide dismutase activity decreased significantly with age in all five tissues studied. The activity of catalase decreased with age in brain, hepatocytes, and kidney while glutathione peroxidase activity decreased significantly with age only in intestinal mucosa and kidney. The relative levels of superoxide dismutase, catalase, and glutathione peroxidase mRNA were measured in brain, hepatocytes, and kidney. An age-related decrease in SOD and catalase mRNA was observed for brain, hepatocytes, and kidney. GPX mRNA levels decreased with age in hepatocytes and kidney but did not change with age in brain. In general, the age-related changes in the activities of SOD, catalase, and GPX were paralleled by a similar change in the relative level of the mRNAs coding for these enzymes. PMID- 2325441 TI - Changes in frequency and localization of human X- and Y-chromatin bodies at interphase during in vitro cellular aging. AB - We have investigated the degree of hypodiploidy of human X (inactive) and Y chromosomes and their relative localization in the interphase nuclei during in vitro aging of diploid fibroblasts. It is found that significant proportions of both female and male cells lose the inactive X and Y chromosome, respectively during cellular aging. Our results from fibroblasts are consistent with comparable findings of other investigators utilizing lymphocytes and bone marrow cells. However, we have observed a relatively higher proportion of X and Y chromosomal hypodiploidy in older fibroblasts than the frequencies reported for lymphocytes or bone marrow cells from aged people. Significant changes in the relative localization pattern of the inactive X and Y chromosomes in the nuclei are also noted during in vitro aging of female and male cells, respectively, and these changes in localization pattern are not identical in both sexes. We believe that, during cellular aging, the analysis of sex chromosomal aneuploidy at interphase is highly likely to provide more accurate results as opposed to the analysis of metaphase chromosomes since the latter is dependent upon the divisional capacity of cells which declines with age. Analysis of interphase cells also avoids the artifacts that accompany metaphase chromosome preparations. PMID- 2325442 TI - Evolution, age and ocular focus. AB - A number of hypotheses has been advanced during the last 130 years to explain the progressive loss of accommodation of the human crystalline lens. None has dealt with the high initial value of accommodation which enables infants to form sharp retinal images of objects as close as 6 or 7 cm. This paper attempts to relate the initial value to the overall loss in terms of evolution and biological cost. PMID- 2325443 TI - Long-term food restriction depresses serum thyroid hormone concentrations in the rat. AB - Long-term food restriction exerts an anti-aging action in rodents. The mechanism underlying its modulation of aging processes is unknown but changes in endocrine systems have been postulated as couplers of food restriction to aging. The effects of long-term food restriction on the serum concentrations of thyroid hormones were examined in 6-month-old, male Fischer 344 rats. For 4.5 months a Food Restricted group was fed 60% of the amount consumed by an Ad Libitum group. Food restriction did not alter the 24-h mean T4 concentration but reduced the 24 h mean T3 concentration from 95 +/- 1 to 87 +/- 3 ng/dl. The Ad Libitum group exhibited diurnal rhythms in both serum T4 and T3 concentrations, with peak values for each hormone at 1000 h. Although food restriction eliminated the 1000 h peak for both thyroid hormones, it abolished the diurnal variation only for T3. The dietary-induced changes in serum T4 and T3 are consistent with a role for these hormones in the anti-aging action of food restriction. PMID- 2325444 TI - ADP-ribosylation of HMG proteins and its modulation by different effectors in the liver of aging rats. AB - The in vitro ADP-ribosylation of high mobility group (HMG) non-histone proteins and its modulation by spermine, butyrate, dexamethasone and 3-aminobenzamide were studied in the liver of young (14 weeks) and old (113 weeks) male rats. ADP ribosylation of HMG 1 was similar in both ages, whereas that of HMG 2 and 14 decreased but HMG 17 increased in the old. HMG 1 was ADP-ribosylated to a greater extent in young but to a lower level in the old by different effectors except spermine which showed no influence in old age. ADP-ribosylation of HMG 2 was stimulated by spermine, butyrate and dexamethasone in old but only by spermine in young rats. Other effectors decreased the ADP-ribosylation of HMG 2 in young. The ADP-ribosylation of HMG 14 was stimulated by spermine in the old but that of HMG 17 was reduced by butyrate in young and by spermine in the old. Dexamethasone decreased the ADP-ribosylation of both HMG 14 and 17 in young, whereas this showed no change in old age. Aminobenzamide inhibited ADP-ribosylation of only HMG 2 in young but all HMGs except HMG 2 in the old. Such alteration in the ADP ribosylation of HMG proteins may affect various cellular and nuclear functions of rat liver during aging. PMID- 2325445 TI - Laser probe temperature control by measuring the returning infra-red radiation. AB - The metal-tipped fibre or 'laser probe' developed for angioplasty comprises a metallic probe at the end of an optical fibre. The probe is heated by an argon or Nd:YAG laser and applied against the tissue to be vapourized. The heated probe generates infra-red radiation which is proportional to the temperature of the probe. The paper investigates the feasibility of a feedback control system that measures the temperature of the probe by detecting the infra-red radiation transmitted back through the fibre. The probe was initially heated by physical contact with a hot surface, and then by an argon laser via the optical fibre. The returning IR radiation was sensed by a lead sulphide detector, while probe temperature was simultaneously measured by a thermocouple. Temperatures as low as 200 degrees C were measured through a 5 m long fibre during the laser heating of the probe. The detector signal increased in an exponential fashion as the probe temperature increased. A resolution of 1 degree C was obtained at a probe temperature of 400 degrees C. It can be concluded that, for the laser probe, it is feasible to use a feedback control system which measures the infra-red radiation transmitted back through the same fibre that carries the heating laser light. PMID- 2325446 TI - Behaviour space of a stretch reflex model and its implications for the neural control of voluntary movement. AB - A nonlinear model for the stretch reflex has recently been used to study the interactions between voluntary and reflex controls during fast, targeted movements. The present study explores the topography of a 'behaviour space' generated by computer simulations of this model under various combinations of values for the gain parameters and time constants in the model's feedback loops. In general, we define a behaviour space to be any set of behavioural characteristics of the simulated movement, such as movement time, peak acceleration or peak velocity. The mathematical model can therefore be viewed as an M x N dimensional map from its parameter space N to a behaviour space M. Here, a one-dimensional behaviour space is explored. This provides a method for quantitatively comparing the different control strategies that might be employed by the nervous system for integrating reflex and descending signals during fast, voluntary movements. The results indicate that an optimal strategy will employ proprioceptive feedback as a means of fine-tuning the braking and clamping activities of fast, goal-directed movements and that descending signals are primarily important for initiating the movement and for controlling reciprocal patterns of muscle activity during the end phase of the movement. PMID- 2325447 TI - Power spectra of extracellular potentials generated by an infinite, homogeneous excitable fibre. AB - The power spectra of the extracellular potentials (EPs) generated under activation of an infinite, homogeneous excitable fibre immersed into an infinite, resistive, isotropic and homogeneous volume conductor are theoretically analysed. The changes in the power spectrum related to the changes in the propagation velocity v, amplitudes Vm and duration Tin of the intracellular action potential (IAP) are analytically determined. It is found that in the ultra-low-frequency region the EP spectral power follows the course of alteration in the square of the modified Bessel function of the second kind and order zero multiplied by the fourth power of the frequency, and the Tin can be assessed by the deviation of the EP power spectrum from this function. It is shown why the sensitivity of the spectral characteristics depends substantially on the radial distance yo from the activated fibre to the point of observation; why the total spectral amplitude depends directly on the IAP wavelength but the total spectral power depends on the IAP wavelength as well as on its duration and propagation velocity; and why the EPs are not proportional to the IAP second spatial derivative even in close proximity to the fibre. PMID- 2325448 TI - Neurophysiological and technical considerations for the design of an implantable phrenic nerve stimulator. AB - Sequential stimulation during one muscle contraction of several compartments of a motor nerve, using multiple-electrodes, allows individual nerve-muscle compartments to be stimulated at fairly low frequencies. This provides time for recovery even during muscle contraction. However, the whole muscle is stimulated at near to its optimum fusion frequency, which provides smooth muscle contraction. This stimulation system imitates the natural activation of skeletal muscle. The new phrenic nerve stimulator described utilises the principle of sequential motor nerve stimulation. It also incorporates a sigh function. The sigh current recruits additional axons at certain intervals and thus creates and keeps available a reserve of conditioned muscle. Clinical advantages result: the conditioning phase after the beginning of long-term phrenic nerve stimulation for electroventilation is shortened and muscle fatigue is delayed. A need of increase of gas exchange can be answered by increasing tidal volume instead of respiration rate alone. PMID- 2325449 TI - Two-frequency impedance plethysmograph: real and imaginary parts. AB - A four-channel impedance plethysmograph has been designed. Impedance signals are obtained at two frequencies by measuring both real and imaginary parts. Particular attention has been paid to the sine wave generation circuits that provide system versatility. The required phase-sensitive demodulation is achieved by means of analogue multiplexers. Results show that there are significant variations in the thoracic equivalent capacitance related to respiration and that there is an increased sensitivity to cardiac activity at low frequencies. PMID- 2325450 TI - Pressures generated by rib cage and abdominal compressions during cardiopulmonary resuscitation. AB - When the rib cage and abdomen are compressed during cardiopulmonary resuscitation (CPR), the effect on intrathoracic pressure, and therefore on haemodynamics, cannot be quantitatively predicted without a physiologically based mathematical model of chest wall dynamics. Using such a model, we compared model simulations of pleural Ppl and abdominal Pab pressures with those from dog experiments in which the compression of the rib cage was delayed from 0 to 500 ms after compression of the abdomen. Integrals of Ppl and transdiaphragmatic pressure, Pdi = Pab-ppl, over their positive and negative values during a cycle were chosen as indices of driving pressures for cardiac output. Both from the model output and experimental data, we found that the positive ppl integral PPI tends to increase with a longer delay between rib cage and abdominal compressions. The negative ppl integral NPI, however, tends to decrease according to the model predictions and data. Furthermore, the positive and negative integrals of Pdi also tend to change with delay time in the opposite way, as shown by both the model simulations and the experiments. Our results show that chest wall tissues modify the externally applied pressures, thereby not allowing us to use the externally applied pressure sources directly as the driving pressure of the cardiovascular system under study. The optimal conditions for haemodynamics during CPR require a compromise between the positive and negative integral indices. Prediction of the optimal haemodynamics from externally applied pressures requires the coupling of appropriate physiological models of chest wall dynamics and haemodynamics. PMID- 2325451 TI - Improved computation of respiratory resistance as measured by transiently increased resistance. AB - The authors have previously described an automated system for measuring total respiratory resistance. The technique used by this system involves a transient, externally applied increase in resistance to breathing. The utility of this technique is limited by a number of assumptions and to free it from the constraints imposed by one of these assumptions a new method for analysing the data was developed. The paper describes the new method of analysis and presents data comparing the resulting Rrss with those computed using the old method. PMID- 2325452 TI - New algorithm for QT interval analysis in 24-hour Holter ECG: performance and applications. PMID- 2325454 TI - Determination of bioluminescence from human subjects by two different methods. PMID- 2325453 TI - Microcomputer-based system for monitoring motor activity. PMID- 2325455 TI - Source of the slippage in the universal joints of the Hoffmann external fixator. AB - An investigation was conducted to determine what improvements in the resistance to slippage could be obtained in selected interfaces (rod/clip torsional, cheek/bowl and cheek/clip) of the Hoffmann external fixator. The modification involved changing the standard wing-nut clamp for a bolt with a thread of 7 mm and a 1 mm pitch and placing an FAG 28-303 thrust-bearing (needle roller and cage assembly) between the bolt and the cheek. The results showed a significant improvement in the slippage values of all interfaces; increases of approximately six times were obtained at all torque values of the wing-nut clamp or fastener tested. Such improvements would markedly increase the reliability of external fixation systems and thus reduce the incidence of loss-of-reduction of fracture due to slippage of the universal joint. PMID- 2325456 TI - 'Real time' transient averaging of cardiac synchronised signals and its application to the tooth pulse. PMID- 2325457 TI - Fibre-optic force recording of mechanical contact between teeth. PMID- 2325458 TI - Pulse-capture circuit for microcomputer data acquisition. PMID- 2325459 TI - Low inertia, rigid limb fixation using glass fibre casting bandage. PMID- 2325460 TI - A device for the accurate production of tailored excitation pulse trains in NMR spectroscopy. PMID- 2325461 TI - [Omeprazole: chemical structure and mode of action]. PMID- 2325462 TI - [Neuroleptic malignant syndrome. Analysis of 9 cases]. AB - The malignant neuroleptic syndrome (MNS) is an idiosyncratic reaction to neuroleptic drugs. Although it was described in the sixties, it is still a poorly known condition. Controversy still exists about its conceptual frame, and its true incidence is still unknown. We have evaluated 9 cases of MNS seen in a 37 month period. There were 5 females, with a mean age of 50 years. Haloperidol, either single or in association, was the most commonly implicated drug. The estimated frequency of MNS in our population at risk was 1.5%. Eight patients had complications and 5 died from them (55%). We discuss the pathogenetic mechanisms, the conceptual characterization and the current diagnostic criteria. We evaluate the causes of the high mortality in our series. We think that a higher suspicion index of this condition would be desirable, and we recommend early treatment with vigorous supportive measures and drug therapy. We think that prospective studies are required to assess the true incidence of MNS. PMID- 2325463 TI - [Treatment of macroprolactinomas with delayed bromocriptine. Effectiveness of a single intramuscular injection]. AB - The aim of the present study was to evaluate the effectiveness and tolerance of a new pharmaceutical preparation of long acting bromocryptine (bromocryptine depot of L.A.), characterized by the slow release of bromocryptine during 4 or 6 weeks after a deep intramuscular injection. It was administered to 9 patients with macroprolactinoma, 7 of which had visual abnormalities. The tolerance of the drug was excellent, and only one patient had nausea within the first 24 hours. In all cases, PRL values fell between 40% and 97%. All patients with visual abnormalities, including 2 patients with cranial nerve palsy (IIIth and VIIth pairs) returned to normal or improved. In the CT controls carried out after 4 weeks of therapy a reduction in tumor size was observed in 7 of 9 patients. Two patients were operated through the transesphenoidal route, PRL being demonstrated in the immunohistochemical study of the resected specimen. Subsequently, all patients received oral bromocryptine therapy with perfect tolerance. The results show that parenteral long acting bromocryptine is an effective, well tolerated and convenient way to start the therapy of macroprolactinoma, even when severe visual abnormalities are present. PMID- 2325465 TI - [Stress, today]. PMID- 2325464 TI - [Reactive hemophagocytic syndrome: analysis of a series of 7 cases]. AB - We report a series of seven patients with reactive hemophagocytic syndrome, which was quite characteristic of its etiological spectrum. Infections were the leading cause, among them a case associated with HIV and another one with Salmonella enteritidis (a hitherto unreported association). The clinical findings consisted of fever, hepatomegaly, splenomegaly, lymphadenopathy, rash and pancytopenia. The diagnosis was carried out by bone marrow aspiration-biopsy except in two patients who were diagnosed at autopsy. The difficulty of the differentiation from malignant histiocytosis is discussed: one case of hemophagocytic syndrome due to diphenylhydantoin toxicity (the second reported one in the literature) was histologically undistinguishable from it. We think that, in any etiology, hemophagocytic syndrome is a reactive syndrome with variable intensity. The need for extensive microbiological investigation even in cases of histiocytosis of neoplastic appearance is emphasized. PMID- 2325466 TI - [Progressive disease and ethics]. PMID- 2325467 TI - [Subacute kidney insufficiency in exclusively vascular kidney amyloidosis]. AB - Two patients are reported with secondary amyloidosis in whom renal biopsy disclosed massive amyloid deposition with exclusively extravascular localization. In one case, autopsy showed selective amyloid deposition in the vessel walls of most examined organs. In both patients, the clinical presentation consisted of subacute renal failure without proteinuria. A possible reduction of renal perfusion, secondary to a depleted blood volume in one case and to pharmacological inhibition of prostaglandin synthesis in the other, could enhance renal dysfunction in both patients, who, on the other hand, previously had mild renal failure. The clinical presentation of renal amyloidosis basically depends on the distribution and severity of amyloid deposits. Vascular localization represents an uncommon pattern of renal amyloidosis, generally associated with chronic renal failure with minimal or no proteinuria. PMID- 2325468 TI - [A 16-year-old woman with pulmonary nodules]. PMID- 2325470 TI - [Participation of primary health care in medical education]. PMID- 2325469 TI - [Endobronchial tuberculosis]. PMID- 2325471 TI - [Meningitis caused by Salmonella non typhi, hemophilia and human immunodeficient virus infection]. PMID- 2325473 TI - [Attempted self-poisoning with xylene ingestion]. PMID- 2325472 TI - [Thyrotoxic periodic paralysis]. PMID- 2325474 TI - [Impetigo herpetiformis as initial manifestation of primary hypoparathyroidism]. PMID- 2325475 TI - [Age as a prognostic factor in intensive care]. AB - In order to define the prognostic impact of the age of critical patients as well as its association with the initial severity of illness (SAPS index) and therapeutic effort (TISS index), we studied 1.102 patients older than 14 years admitted consecutively to 3 general intensive care units. The oldest patients (more than 65 years) showed a higher mean SAPS (11.00 versus 8.58, p less than 0.0001) and mortality (odds ratio = 1.99, p less than 0.0001) than the younger ones. The association between age and mortality showed a "dose-response" pattern, even after controlling for the effect of initial severity (p less than 0.0001). The effect of age was stronger in the groups of patients with low SAPS (odds ratio = 2.94, p = 0.0007) or admitted for acute myocardial infarction (odds ratio = 3.28, p less than 0.0001). The oldest group showed a lower TISS/SAPS ratio and a shorter stay in the intensive care unit than younger patients, suggesting a low relative therapeutic effort in the latter. The differential therapeutic effort did not explain, however, the mortality excess in the oldest group, because the gradient of mortality increased after adjusting for TISS/SAPS ratio (adjusted odds ratio = 2.42, p less than 0.0001). PMID- 2325477 TI - [Visceral leishmaniasis: a new opportunistic infection in carriers of the human immunodeficiency virus]. PMID- 2325476 TI - [Hepatitis B and hepatitis delta in young inmates]. AB - The prevalence of infection by hepatitis B (HBV) and delta (HDV) viruses and presumably related variables were evaluated in a prison for young male convicts, aged 16-21 years (n = 686), 55.1% of convicts were positive for one or more VHB markers, and 7.1% were positive for HBsAg; 89.7% of these were negative for IgM anti-HBc (chronic carriers), while 36.6% were positive for HBeAg. Anti-delta antibodies were detected in 37.5% of chronic carriers. The seropositivity of HVB markers was much higher in parenteral drug abusers (PDA) as compared with non PDA (76.3% vs 26.7%, p less than 0.0000001, OR = 8.82). Among PDA, it was higher in regular users than in occasional ones (83.3% vs 62.9%, p = 0.0001, OR = 2.95) and in those who had acquired the habit at an early age (p = 0.035). The stratified analysis also showed an association of VHB infection with other variables, basically ethical and prison-related. The possibility to develop active immunization programs is evaluated. PMID- 2325478 TI - [Graft vs host disease of the skin]. PMID- 2325479 TI - [Treatment with interferon of systemic Langerhans-cell histiocytosis in an adult]. AB - We report an adult patient with systemic Langerhans' cell histiocytosis (LHX), who was refractory to multiple chemotherapy courses and in whom a partial clinical and biological 3-month remission was achieved with alpha-2-interferon. The patient's response was associated with an increase in the rate of natural killer cells and to a return to normal of the H/S T-lymphocyte ratio. Immunological abnormalities have been reported in this condition, and it is now accepted that the most important one is a decrease in suppressor lymphocytes. However, it is not known whether these abnormalities are endogenous or exogenous. The experience with modifiers of the biological response for the treatment of LHX is scanty, but the probable immunological pathogenesis of the condition justifies a therapeutic trial of those agents in patients not responding to conventional therapy. PMID- 2325480 TI - [Anaphylactic shock caused by amoxicillin with good tolerance of penicillin]. PMID- 2325482 TI - [Which Spanish journals are included in international biomedical indexes?]. PMID- 2325481 TI - [Asymptomatic visceral leishmaniasis in a patient with acquired immunodeficiency syndrome]. PMID- 2325483 TI - [Immunosuppression with cyclosporin A and pregnancy]. PMID- 2325484 TI - [Acquired immunodeficiency syndrome and adrenal gland insufficiency]. PMID- 2325485 TI - [A prospective study on the time elapsed until admission at the coronary unit of patients with acute myocardial infarct. Apropos of 180 cases]. AB - We have carried out a prospective study to evaluate the time from the onset of symptoms until the admission to coronary care unit in 180 patients with acute myocardial infarction. We have evaluated the causes resulting in a delay and their consequences on the prognosis. The data were obtained with a clinical questionnaire from the patients and/or his family and from a review of the clinical records. The mean time since the onset of symptoms until the admission to the coronary care unit was 5.4 hours, being significantly shorter in the patients who did not call for prehospital attention. The major delay was attributable to the patient (delay in asking for medical attention); therefore, it is mandatory to implement measures of health education. Prehospital attention did not provide any diagnostic or therapeutic improvement in 30% of patients. Thus, we suggest that community care education on coronary artery disease should be improved. PMID- 2325486 TI - [Primary malignant melanoma of the skin. Retrospective study of 375 cases. Clinical aspects and histology]. AB - The clinical and histologic features of 375 cases of primary malignant melanomas of the skin diagnosed and/or treated in the Hospital Clinic i Provincial (Barcelona, Spain) over a seven years period (1981-1987) were evaluated. The analysis of data showed many differences between these cases and those previously reported by us or from other countries. Sex incidence showed an increased frequency in women (58%), and a high incidence on lower limb in female (26% of all cases). Superficially spreading melanoma was the most common type (58%), followed by nodular melanoma (27%), acral lentiginous melanoma (8%) and lentigo maligna melanoma (6%). 57% of cases were diagnosed when the tumor thickness indicated a moderate or high-risk. PMID- 2325487 TI - [121 cases of decompression disease]. AB - One hundred and twenty-one subjects with decompression disease (DD) treated by the Spanish Navy between 1969 and 1986 are reported. The mean age of the victims was 31.4 +/- 7.2 years. The leading cause of DD was the partial or complete omission of decompression. The development of type I DD (57%) (basically joint pain) was more common than type II (43%) (neurological vestibular and/or pulmonary features). In 84.3% of cases the clinical features began within 6 hours of the end of immersion, although only 61.5% were treated during the initial 6 hours. When therapy was delayed for longer than 6 hours, the rate of sequelae was considerably increased. The rate of complete recovery after treatment in a compression chamber was 92.7% for type I DD and 71.1% for type II DD. PMID- 2325488 TI - [Rapid transfer to the coronary unit of patients with acute myocardial infarct. Justification of the necessity and action measures]. PMID- 2325489 TI - [Transcortical motor aphasia caused by meningioma]. PMID- 2325490 TI - [Paralysis caused by tick bite]. PMID- 2325491 TI - [Gigantic Molluscum contagiosum in systemic lupus erythematosus]. PMID- 2325492 TI - [False positivity of the Paul-Bunnell-Davidsohn reaction in acute infection caused by the human immunodeficiency virus]. PMID- 2325493 TI - [Effect of a case of active tuberculosis on a closed community of students]. PMID- 2325494 TI - [Muscle contraction as the presenting form of Addison's disease]. PMID- 2325495 TI - [Askin tumor with infiltration of the optic nerves and diabetes insipidus]. PMID- 2325496 TI - [Psychological disorders of a somatic type]. PMID- 2325497 TI - [Tamoxifen as a risk factor for endometrial cancer]. PMID- 2325498 TI - [Can copper cause fatal liver cirrhosis in infants in Sweden?]. PMID- 2325499 TI - [Radiation risks are evaluated. There is no totally harmless level]. PMID- 2325500 TI - Changes in renal, platelet and cardiac nitrobenzylthioinosine binding in spontaneously hypertensive rats. AB - In an attempt to investigate the role of nucleoside transporter function in the hypertensive state, we have compared the binding of [3H]nitrobenzylthioinosine ([3H]NBMPR), a nucleoside transporter probe, in membranes prepared from platelet, renal, pulmonary, cardiac and brain tissues of spontaneously hypertensive rats (SHR) to those of age-matched Wistar-Kyoto (WKY) controls. At 4 weeks of age, [( 3H]NBMPR) binding sites (Bmax) increased in the kidney of SHR but decreased in platelets, whereas no changes were found in the heart, lung or brain. At 18 weeks of age, [3H]NBMPR binding sites (Bmax) remained increased in the kidney and decreased in platelets with no changes in the other tissues. The only change in apparent binding affinity (KD) was an increase in the heart of SHR at 4 weeks. Age-dependent decreases were also observed in the heart and platelets of both SHR and WKY at 18 weeks. The results indicate that the changes in binding characteristics may be due to a combination of the pharmacodynamic differences between the strains, age, as well as to the pathogenesis of hypertension. Consequently, it cannot be concluded that the altered binding characteristics are the result of the elevated blood pressure. PMID- 2325501 TI - The effect of clozapine on prolactin secretion at the level of the lactotroph. AB - Clozapine is an antipsychotic drug which is unusual in that it has no dopamine receptor-blocking activity. Previous studies gave conflicting results whether administration of clozapine induces hyperprolactinemia. In the present study it was shown that a wide concentration range of clozapine does not interfere with dopamine-mediated inhibition of prolactin (PRL) secretion by normal cultured rat pituitary cells. This in contrast to other neuroleptics, like haloperidol and trifluoperazine. Clozapine does also not antagonize norepinephrine-mediated inhibition of PRL secretion. Clozapine exerts at micromolar concentrations a direct inhibitory action on PRL release by cultured normal rat pituitary cells. In cultured rat pituitary tumor cells, these high concentrations of clozapine directly inhibit PRL release as well as the DNA content of the cells, suggesting a direct antimitotic action. In this model clozapine was about 5-10 times less potent than trifluperazine. Clozapine and trifluoperazine exert an additive inhibitory action both on PRL release and on the DNA content of the pituitary tumor cells. It is concluded that clozapine does not interfere at the pituitary level with dopamine-mediated inhibition of PRL release. At micromolar concentrations clozapine may act on lactotrophs as a calmodulin-inhibitor. These observations suggest that the transient PRL-releasing effects which have been observed in both animal and human studies after clozapine administration are mediated via supra-pituitary actions of the drug. PMID- 2325502 TI - Cyclosporine lowers seizure threshold in an experimental model of electroshock induced seizures in Munich-Wistar rats. AB - We have developed a model of cyclosporin A (CsA) central nervous system toxicity in the Munich-Wistar rat in which CsA, 20 mg/kg/day i.p., produces significant EEG abnormalities and mortality. In the present study we used cohorts of Munich Wistar rats to assess effects of CsA on the threshold for tonic-clonic electroshock-induced seizures. Rat cohorts were begun on cremephore, CsA-10 mg/kg/day, or CsA-20 mg/kg/day. On day 7 and day 14 of the dosing protocol, cohorts of animals were exposed to maximal electroshock (MES) using a minimal staircase method within each cohort. Multiple logistic regression models were used to determine differences between groups on the relative odds of producing a MES-induced seizure while controlling for other variables. Seizure threshold was significantly affected by shock amperage and body weight, but not by SUN, creatinine, bilirubin, sodium, potassium, weight loss or day the shock was delivered. The odds ratios of seizure induction in the CsA-treated groups versus placebo group were 1.91 for CsA-10 mg/kg/day and 3.63 for CsA 20-mg/kg/d, both statistically significant. These results suggest that cyclosporine lowers seizure threshold and probably increases susceptibility to seizures, the etiology of which may be multifactorial clinically. PMID- 2325503 TI - Impaired recovery of brain muscarinic receptor sites following an adaptive down regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats. AB - Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP (doses in mg/kg: first 1.1, two of 0.7 and four of 0.35) on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there was a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration (for many hours after each injection), in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment (about 70%) did not differ between young and surviving aged rats. The down-regulation of mAChRs (without changes in affinity) was present in the three brain regions of both young and aged rats (from 20 to 40%). Factorial analysis of variance (2 ages x 2 recoveries ANOVA) showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in the three brain areas. For example, cortical ChE in young rats reached pretreatment levels within 3 weeks, while hippocampal and striatal ChE activity recovered within 4 weeks; at these intervals ChE activity in aged rats was still considerably reduced (except in the striatum). Cortical and striatal mAChRs in young rats almost normalized within 1 week and hippocampal mAChR binding sites normalized within 2 weeks; at these intervals Bmax in aged rats were markedly below control levels. The overall data indicate that the recovery rate to normal baseline levels of ChE activity and mAChRs, following the termination of repeated treatment with the antiChE agent, is impaired in brain of aged rats. The delay in recovery rate is particularly evident in the cerebral cortex. PMID- 2325504 TI - Intestinal absorption of unconjugated dihydroxy bile acids: non-mediation by the carrier system involved in long chain fatty acid absorption. AB - Experiments were performed using isolated mucosal cells from the rat jejunum or using the perfused jejunum in the anesthetized rat to test whether lipophilic unconjugated dihydroxy bile acids are absorbed from the proximal small intestine via the same carrier mechanism involved in the uptake of long chain fatty acids. With isolated jejunal mucosal cells, the cellular uptake rate of deoxycholic acid or chenodeoxycholic acid increased linearly with time, showed no evidence of saturation, and was not decreased by the presence of a monospecific antibody to the membrane fatty acid binding protein. In contrast, oleate uptake was saturable, was inhibited by the same antibody, but was not affected by the presence of chenodeoxycholic acid or deoxycholic acid. Bile acid uptake by isolated enterocytes occurred at one-eighth the rate of fatty acid uptake if expressed in relation to total solute concentration; if expressed in relation to monomeric concentration, initial bile acid uptake was four orders of magnitude slower than fatty acid uptake. In the isolated perfused jejunal segment, chenodeoxycholic acid and deoxycholic acid uptake was not influenced by the presence of the antibody to membrane fatty acid binding protein, whereas absorption of oleate was inhibited by more than 70%. These experiments indicate that absorption of unconjugated lipophilic dihydroxy bile acids in the rodent jejunum does not involve the carrier mediated uptake mechanism involved in the absorption of long chain fatty acids--the mechanism is likely to be passive nonionic diffusion. PMID- 2325505 TI - The uptake of (R,R,R)alpha-tocopherol by human endothelial cells in culture. AB - Endothelial cells from human umbilical cord vein in culture incorporate physiological and pharmacological amounts of (R,R,R)alpha-tocopherol in a time dependent and dose-dependent manner. Incorporated tocopherol was found to associate predominantly with membrane fractions of the cell. When expressed on the basis of organelle protein, the highest amount of tocopherol was found in plasma membrane, and decreasing amounts in mitochondria, endoplasmic reticulum and cytosol. With the relatively wide range of tocopherol concentrations used in these studies (23.2-92.8 microM), there was no apparent toxicity on the cells as judged by unaltered cell numbers and cell viability. When the cells were enriched with tocopherol and cell tocopherol levels were monitored in tocopherol-free medium, there was a rapid phase of tocopherol disappearance, which was followed by a slower phase. The half-time for the disappearance of incorporated tocopherol was found to be approximately 65 +/- 8.6 hr (mean +/- SD, n = 3). The results of this study clearly show that human endothelial cells in culture are a feasible model for the study of vitamin E uptake. The cell culture model could potentially be used to study other fat-soluble vitamins and essential nutrients. PMID- 2325506 TI - Identification of vitamin E-dependent water soluble fluorescent compounds in mouse tissues. AB - The present paper describes the identification of two vitamin E-dependent, water soluble fluorescent compounds in mouse tissues. Ultraviolet and fluorescent spectroscopy, derivatization with 1-dimethylamino-naphthalene-5-sulfonyl chloride (dansyl chloride) and cochromatography using high performance liquid chromatography (HPLC) were utilized for the identification of the unknown compounds. The water soluble fluorescent compounds in mouse tissues were identified as tyrosine and tryptophan. The compounds were previously found to increase significantly in vitamin E deficiency in various tissues. PMID- 2325507 TI - Effects of dietary fish oil on biliary phospholipids and prostaglandin synthesis in the cholesterol-fed prairie dog. AB - Cholesterol gallstone formation in the prairie dog is accompanied by an increase in the percentage of biliary phospholipids containing arachidonic acid, and an increase in gallbladder prostaglandin (PG) synthesis, but the pathogenetic significance of these changes is unclear. Dietary supplementation with eicosapentaenoic acid (EPA), an omega-3 fatty acid which is commonly found in fish oil, decreases prostaglandin synthesis in some tissues by replacing arachidonic acid, and by competitively inhibiting prostaglandin synthesis. We studied the effect of dietary fish oil on gallbladder PG synthesis, and the relative abundance of various molecular species of phosphatidylcholines and phosphatidylethanolamines in bile and gallbladder epithelium in the cholesterol fed prairie dog. Prairie dogs were maintained for 4 weeks on one of four diets: i) control, ii) cholesterol-supplemented (0.34%), iii) menhaden oil (50 g/kg chow), or iv) cholesterol plus menhaden oil. Supplementation with menhaden oil resulted in a replacement of arachidonic and linoleic acids with EPA and docosahexaenoic acids in the phospholipids of bile and gallbladder mucosa. In cholesterol-fed animals, supplementation with menhaden oil prevented increased gallbladder PG synthesis. Menhaden oil also reduced the incidence of cholesterol monohydrate crystals among cholesterol-fed animals (9/20 with cholesterol plus menhaden oil vs 21/22 with cholesterol alone), but the improvement could not clearly be attributed to decreased PG synthesis since supplementation with menhaden oil also increased the total phospholipid concentration in bile, and decreased the degree of cholesterol saturation. These results demonstrate that dietary supplementation with omega-3 fatty acids significantly influences biliary phospholipids, and decreases the incidence of cholesterol monohydrate crystal formation in this animal model. PMID- 2325508 TI - Binding of galactosylsphingosine (psychosine) by albumin. AB - On applying [3H]galactosylsphingosine (psychosine) and albumin to a gel filtration column, either as a pre-incubated mixture or as separate solutions, the lipid and albumin co-eluted. When albumin and [3H]galactosylsphingosine were incubated with Sephadex G-50, the concentration of galactosylsphingosine outside the gel increased as the concentration of albumin increased. These observations indicate that albumin binds galactosylsphingosine. By using an equilibrium gel procedure, it was estimated that one molecule of albumin has 7.4 binding sites for galactosylsphingosine, and that the dissociation constant is 3.9 X 10(-6) M. These values appear compatible with the potency of albumin to suppress galactosylsphingosine-induced hemolysis. PMID- 2325509 TI - Identification of the new 23-methyl-5,9-pentacosadienoic acid in the sponge Cribrochalina vasculum. AB - The phospholipid fatty acids from the sponge Cribrochalina vasculum were studied, revealing the presence of the new 23-methyl-5,9-pentacosadienoic acid (26:2) which completes the iso-anteiso 26:2 (delta 5,9) series. Other phospholipid fatty acids isolated include 26-methyl-5,9-heptacosadienoic (28:2) and 25-methyl-5,9 heptacosadienoic (28:2), as well as the branched acids 8-methylhexadecanoic and 11-methyloctadecanoic. The fatty acids described in this work were found in phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. The sterol composition of C. vasculum consisted of petrosterol, an interesting cyclopropane containing sterol, and the more common sitosterol. The phospholipid fatty acid composition of the demosponge Ircinia strobilina is also reported upon. PMID- 2325510 TI - Some legal issues of turf: relation to magnetic resonance. PMID- 2325511 TI - RASEE: a rapid spin-echo pulse sequence. AB - Most fast-imaging sequences use gradient echoes and a low flip-angle excitation. The low flip angle is used because it gives increased signal when TR less than T1. However, spin-echo sequences are less productive of certain artifacts, among them flow and magnetic susceptibility artifacts. We present a modification of the spin-echo pulse sequence designed to optimize the signal-to-noise ratio for repetition times (TR) less than 100 msec while preserving good image quality. Our implementation performs a 128 x 128 image in under 7 sec (TR = 50 msec) and has been used to follow the dynamics of Gd-DTPA in the rat kidneys. PMID- 2325512 TI - Radio frequency field intensity mapping using a composite spin-echo sequence. AB - A novel radio frequency (RF) field intensity mapping or imaging method using a composite NMR spin-echo sequence is proposed. A composite spin-echo RF pulse with 90 degrees y-180 degrees x-90 degrees y sequence makes phase change in the final image depending on the RF field intensity on the object. The resultant phase change or phase map can be used to obtain the actual RF flip-angle map for a given condition which includes the status of tuning and RF inhomogeneity, etc. Bloch equation has been solved numerically to obtain the effects of the RF field intensity as well as the main magnetic field inhomogeneity and the results are used for the mapping (imaging) of the RF field intensity. Phantom studies have been performed using a 1.5 Tesla whole body MRI system and the results are presented. PMID- 2325513 TI - Bone marrow findings on magnetic resonance images of the knee: accentuation by fat suppression. AB - Long TR/double spin-echo magnetic resonance images of the knee were obtained with and without the use of fat suppression techniques in seven patients with high signal intramedullary lesions. Comparison between images was performed qualitatively and quantitatively. Contrast-to-noise ratios between focal defects and surrounding fatty marrow were higher with fat suppression in all cases. The mean contrast-to-noise ratio for images obtained with fat suppression was 53.6, while for images obtained without fat suppression the mean contrast-to-noise ratio was 17.3 (p less than 0.01). PMID- 2325514 TI - Concomitant magnetic field gradients and their effects on imaging at low magnetic field strengths. AB - Low-field NMR imaging systems which use large amplitude field gradient pulses (e.g., in flow velocity encoding) may be subject to the undesirable effects of concomitant gradients. We demonstrate the effects of these extra gradients, which arise from Maxwell's equations, and show that the resultant image phase shifts and amplitude changes are consistent with theory. PMID- 2325515 TI - Determination of T1- and T2-relaxation times in the spleen of patients with splenomegaly. AB - Twenty-nine patients with known splenomegaly and seven healthy volunteers were examined. The T1 and T2 relaxation times were read out from a region of interest centrally in the spleen. Even though different mean T1 and T2 relaxation times were found between the groups, the great scatter and the considerable overlap between the groups makes the contribution of relaxation time measurements to the differential diagnosis of splenomegaly of limited value. PMID- 2325516 TI - MR pulse sequences for selective relaxation time measurements: a phantom study. AB - The accuracy of relaxation time measurements of spectroscopic inversion recovery and CPMG multi-echo pulse sequences together with ISIS and stimulated echo-pulse methods have been tested on a reference phantom (test object no. 5, of the EEC Concerted Research Project). For the measurements a Siemens Magnetom wholebody magnetic resonance scanner operating at 1.5 Tesla was used. For comparison six imaging pulse sequences for relaxation time measurements were tested on the same phantom. The spectroscopic pulse sequences all had an accuracy better than 10% of the reference values. PMID- 2325517 TI - Separation of spin populations with gradient echoes as an aid in pulse sequence tuning. AB - Tuning of nuclear magnetic resonance pulse sequences with pulsed "crusher" gradients or phase cycling serves to remove unwanted spin populations from the data acquisition window. Verification that unwanted spin population are not detected is often determined by the absence of obvious artifacts in an image. This approach is unsatisfactory in some instances because signal contamination with unwanted spin populations may not be obvious. This is a particular concern with multiple-spin echo, volume-selective, and other multiple-pulse sequences. A solution to this problem is the separation of spin populations using gradient echoes, allowing the existence of unwanted populations to be easily observed separately. Tuning of a pulse sequence is straightforward when spin populations can be independently observed. PMID- 2325518 TI - MRI evaluation of AIDS-related encephalopathy: toxoplasmosis vs. lymphoma. AB - The spectrum of cranial MRI findings was evaluated in 113 patients with the acquired immunodeficiency syndrome, assessing lesion number, size, location, and configuration in association with the autopsy and/or biopsy results. Correlation of cranial MRI and CT was performed in 32 patients. MRI was shown to be superior in sensitivity of lesion detection demonstrating more lesions than CT in 14 studies (44%) and equivalent information in 18 studies (56%). In no case did CT demonstrate lesions not detected on MRI. We conclude that MRI should be the study of choice in evaluating AIDS-related encephalopathy. Multiple lesions that involve both deep gray matter and white matter suggest the possibility of CNS lymphoma. The "target" appearance on MRI is not helpful in distinguishing toxoplasmosis from lymphoma. PMID- 2325519 TI - Short-term exposure to a 1.5 tesla static magnetic field does not affect somato sensory-evoked potentials in man. AB - The literature is contradictory regarding the effect of static magnetic fields on the function of the central nervous system of mammals. Since human subjects are exposed to intense static magnetic fields during magnetic resonance imaging, it is important to determine if the static magnetic field adversely affects the nervous system of man. Therefore, somato-sensory evoked potentials (SEPs) elicited from median nerve stimulation were measured in 11 normal subjects before and during short-term exposure to a 1.5 Tesla static magnetic field. Specially modified instrumentation was used to record SEPs that were unperturbed by the static magnetic field. There were no statistically significant differences in the N20 or P25 latencies or in the amplitude from N20 negative peak to P25 positive peak of the SEPs obtained before compared to those recorded during exposure to the static magnetic field. In addition, there were no changes in the waveforms associated with exposure to the static magnetic field. We conclude that short term exposure to a 1.5 Tesla static magnetic field does not affect SEPs (i.e., nerve conduction and synaptic transmission were within normal limits) in normal human subjects. PMID- 2325520 TI - The use of Gd-DOTA in magnetic resonance imaging of experimentally induced mammary tumors. AB - Gd-DOTA contrast enhancement of MR images was evaluated on induced mammary tumors in female rats. A single intravenous injection of the carcinogenic N-nitrosourea ENU was administered to Wistar rats; this simple treatment led to a high percentage of mammary tumors without causing death. All the induced tumors were adenocarcinoma and their heterogeneousness depended on their size. The induced tumors did not have intra- or extravascular inflammatory spaces caused by heterotopic lesions, as is the case with implanted tumors. Before injection of Gd DOTA, appearance of the patchy internal structure was clearly demonstrated on spin-echo images performed with long repetition times. Three doses of the paramagnetic contrast agent (0.1, 0.2, and 0.5 mmol/kg) were evaluated on two different T1-weighted MR sequences. Images were recorded before and repeatedly after intravenous injection of Gd-DOTA, and signal intensities and relaxation times were measured. On images acquired with the spin-echo 500/28 as well as the inversion-recovery 928/26/300 sequences, the results showed that 0.2 mmol/kg Gd DOTA was the optimal dose for contrast enhancement and for clear visualization of the heterogeneousness of the mammary tumor. PMID- 2325521 TI - Retroperitoneal cystic lymphangioma: MR findings. PMID- 2325522 TI - Magnetic resonance imaging of spinal intradural granulocytic sarcoma. AB - We report the case of a young black male with a spinal intradural granulocytic sarcoma proved by needle aspiration. The tumor was evaluated by myelography, computed tomography, and magnetic resonance imaging (MRI). Other than its rarity, the "dripping candle wax" appearance on MR T1-weighted images and the lack of enhancement with Gd-DTPA makes this case unique. Progressive changes of the tumor following chemo- and radiotherapy were successfully demonstrated by MR. PMID- 2325523 TI - Treatment preferences of patients and physicians: influences of summary data when framing effects are controlled. AB - The presentation of efficacy data influences preferences for treatment options. To determine how the amount of data provided to patients influenced patient decision making after framing and labeling effects were controlled, patients and physicians were presented results of two alternative treatments for an unidentified serious medical condition, derived from summary data of lung cancer treatment after surgery (better long-term survival) or radiation therapy (better short-term survival). These data are the same as used in previous studies of framing. When summary data at one month, one year, and five years were presented in terms of both survival and mortality, patients preferred the option that would be expected if only mortality data had been presented. When more detailed data were presented (data at six discrete time points), both patients and physicians preferred the option associated with a survival frame influence in previous studies. Thus, once framing influences are controlled, preference changes can be influenced by another attribute of summary data: the amount of data presented. PMID- 2325525 TI - Knowing for the sake of knowing: the value of prognostic information. AB - In evaluating diagnostic tests, traditional methods in decision analysis often emphasize how the results of the test will or will not affect patient management. Clinicians are advised to avoid testing if the results will not alter treatment strategy or other management plans. But patients may be interested in the prognostic information that testing provides even if it is not used to guide treatment. The authors present a model that defines this prognostic information as the expected deviation from the prior probability of disease. The model generates utility functions that are curvilinear over prior probabilities. Whereas the traditional threshold approach to medical decision making produces at most three zones of management strategy (withhold, test, and treat), the incorporation of prognostic information into threshold analysis produces two additional zones (test but withhold anyway, and test but treat anyway). Conditions under which one or both of these additional zones will appear are described. The model justifies the practice of performing tests that cannot alter management plans; it explains the unwillingness of some patients to undergo diagnostic testing when they fear unwanted results; and it provides a method for quantifying the sensitive nature of confidential tests. The model is illustrated using the antibody test for the Smith antigen. This test has a high specificity but a low sensitivity for lupus erythematosus. Clinicians may use the test because a positive result will support their prior suspicion of disease even though they may not change their management strategy if the test result is negative. The advantage of testing in this setting lies in the test's potential for establishing with virtual certainty that the disease is present. Thus, the test is valued for the prognostic information it provides apart from its effect on patient management. PMID- 2325524 TI - Receiver operator characteristic (ROC) analysis without truth. AB - Receiver operator characteristic (ROC) analysis, the preferred method of evaluating diagnostic imaging tests, requires an independent assessment of the true state of disease, which can be difficult to obtain and is often of questionable accuracy. A new method of analysis is described which does not require independent truth data and which can be used when several accurate tests are being compared. This method uses correlative information to estimate the underlying model of multivariate normal distributions of disease-positive and disease-negative patients. The method is shown to give results equivalent to conventional ROC analysis in a comparison of computed tomography, radionuclide scintigraphy, and magnetic resonance imaging for liver metastasis. When independent truth is available, the method can be extended to incorporate truth data or to evaluate the consistency of the truth data with the imaging data. PMID- 2325526 TI - What difference do two days make? The inertia of physicians' sequential prognostic judgments for critically ill patients. AB - Medical authorities have asserted the importance of observing a patient's clinical course over time. Distinguished committees have suggested that changes over time in physicians' prognostic estimates should influence decisions to transfer patients out of intensive care units (ICUs). This study evaluated how the opportunity to observe patients over time affected physicians' prognostic estimates for a cohort of 269 critically ill patients sequentially admitted to a medical-surgical ICU in a teaching hospital. As soon as possible after admission and again 48 hours later, the authors obtained a quantitative estimate of the probability of survival through hospital discharge from each patient's house officer and primary attending physician, and the critical care attending physician on duty. They independently determined each patient's survival. From this population they analyzed 181 pairs of judgments made by the same house officers, 211 pairs by the same primary attendings, and 172 pairs by the same critical care attendings. The physicians' 48-hour estimates were little changed from their previous estimates for the same patients. The correlation coefficient for the house officers' paired estimates was 0.84 (p less than 0.0001); for the critical care attendings' estimates 0.84 (p less than 0.0001), and for the primary attendings' estimates, 0.90 (p less than 0.0001). Forty-eight hours did not substantially reduce the disagreements present between estimates made by different physicians for the same patient. No group of physicians substantially improved the reliability or the discriminating power of its later estimates. The physicians in the study could not take advantage of sequential clinical information over time. These results point out the need to teach physicians how to better integrate and process sequential clinical data. PMID- 2325527 TI - N-way sensitivity analysis: a verification and stability-assessment technique for completely subjective decision analysis trees. AB - The purpose of this paper is to describe the development of N-way sensitivity analysis, a modified version of traditional sensitivity analysis that was created for the purpose of verifying the stability of decisions made by a completely subjective decision-analytic tree. The technique was developed during research that addressed whether nurses make clinical decisions that coincide with those recommended by a decision-analytic model. Since all parameters of the model were derived from subjective assessment, traditional one-way or two-way sensitivity analysis was deemed inappropriate. Consequently, N-way sensitivity analysis was developed and used for the verification of the decision model's results. PMID- 2325528 TI - A therapeutic recovery model for the female adult incest survivor. AB - As the prevalence of incest survivors seeking therapy continues to increase, clinicians must expand their knowledge and methods of treatment. This article discusses the development of incest within the family system, the resulting long term effects, and a treatment model developed by the author to guide therapeutic intervention with the adult female survivor. The three-phase Incest Recovery Model provides direction regarding the issues and tasks that each survivor must confront before reaching the therapeutic goals. Phase 1 is conducted in a group setting; Phase 2 in individual therapy and sessions with the survivor's family of origin. Phase 3 concludes with a combination of individual and group sessions. Interruption and reentry of the model may occur at any time; consequently, survivors determine their individual progress. As the psychological burden of incest lessens, survivors are free to adopt healthier patterns of living. PMID- 2325529 TI - The process of coping among young adult children of alcoholics. AB - Children of alcoholics are often misdiagnosed or ignored because of socially acceptable coping styles. These survival coping mechanisms have been identified as specific role behaviors inhibiting normal development. These assumptions, however, have not been tested with rigorous research techniques. The purpose of this study was to describe the developing role patterns and/or coping behaviors of 30 young adult children of alcoholics (ACAs) between the ages of 18 and 28. Data were obtained primarily through in-depth interviews as well as the Jalowiec Coping Scale. Interview responses were analyzed using content analysis procedures and triangulated with questionnaire responses. The findings of this study suggest a possible developmental delay in coping strategies used by children of alcoholics although no specific ACA role behaviors were identified. Confrontive measures of coping did not develop until young adulthood and only after therapeutic intervention. Two unique methods of coping, reversed emotive and reversed confrontive, were also identified. The latter could be peculiar to this population, since it reflected many codependent behaviors. PMID- 2325530 TI - Stigmatization: experiences of persons with acquired immune deficiency syndrome. AB - The purpose of this study was to understand the meaning that being stigmatized has for persons with Acquired Immune Deficiency Syndrome (AIDS). The research question for this investigation was, What is the perception of stigmatization as experienced by persons with AIDS? Phenomenology provided both the theoretical framework and the method for this study. The sample consisted of 10 homosexual men contacted through a New Orleans hospice, home health nurses, the investigator's own personal contacts, and referrals from men who were in the project. Participants were asked open-ended questions pertaining to changes in their relationships with others since diagnosis, changes in self-esteem, and examples of prejudice and discrimination. Interviews were audiotaped, transcribed verbatim, and analyzed using a qualitative approach. The phenomenon of stigmatization emerged as experiences of rejection and protection in social interactions. PMID- 2325531 TI - Biopsychosocial elements of empathy: a multidimensional model. AB - Empathy is a topic of growing concern in a variety of disciplines. Although considerable empathy research is reported, often single dimensions of a multidimensional and multiphasic construct are actually being studied. Empathy is a unitary construct involving biopsychosocial components and is particularly well suited for nursing study because of its theoretical congruence with nursing philosophy and concerns. Empathy's importance goes beyond the usual emphasis on helper empathy. Although commonly associated with prosocial behavior, empathy involves underlying processes which may be used for either positive or negative social purposes. Recent technological improvements in research methodology, concerns regarding social violence, and conceptual shifts have led to greatly increased interest in the phenomenon of empathy and an expanded research thrust. One major recent change in empathy research is the tendency to view the phenomenon as multidimensional and consequently to include a variety of measures to capture different elements of the construct. This paper reviews the major approaches to measurement of empathy and classifies these approaches according to the dimensions of empathy that they measure. Physiological change in association with empathy is less frequently measured, but because empathy is commonly assumed to include an emotional response to another, concomitant physiological changes should accompany the emotional aspect of empathy and indicators of physiological response may be appropriate measures to include in nursing studies of empathy. A conceptualization of empathy is presented that considers empathy to be a multidimensional phenomenon, with emotional, cognitive, communicative, and relational components. Because empirical approaches can only examine the most easily measured aspects of empathy, phenomenological approaches are also needed to begin to capture the total construct. PMID- 2325532 TI - Inpatient survey of nursing care measures for treatment of patients with anorexia nervosa. AB - This study identifies and describes the inpatient nursing treatment and rationale for patients with anorexia nervosa in nationally recognized psychiatric inpatient settings. The study was undertaken to guide planned change in the nursing protocol on the authors' unit. Sixteen units were surveyed in an extensive telephone interview using structured interview guides. Findings indicated that behavioral management with contingency plans was the mainstay of treatment for the patients regardless of the identified unit treatment philosophy. This approach is effective for patient weight gain within an inpatient setting. Based on these data, the authors concluded that the program which was ongoing at their site was more restrictive than that in most other settings. Changes were made in the unit program to lessen the controls. Objective measures of weight and length of stay indicated that patients do as well with the revised plan as they did with the more controlled plan. PMID- 2325533 TI - Psychiatric nurses' and patients' perceptions of discussion topics in therapeutic groups. AB - Discussion topics for outpatient group therapy sessions were rated for importance by 84 psychiatric outpatients from 6 therapeutic groups and 26 psychiatric nurses. Topics were measured by scales of personal problems and feelings, lifestyle, response to health care, and nonhealth self-disclosure. No significant differences in importance ratings among therapeutic groups or between nurses and patients were found. Scale rankings were the same among patient groups and between nurses and patients, with personal problems and feelings receiving the highest score. Results support the existence of a common goal implicit among therapeutic groups that is known by nurses and augurs well for group cohesion, behavior in accordance with norms, and the efficacy of nurses as leaders of therapeutic groups. PMID- 2325534 TI - Modeling the client's world: a way to holistic care. AB - This article examines the differences between wholistic nursing and holistic nursing and proposes that the latter conceptualization is more effective for contemporary nursing care. First, a brief historical overview and critique of the two concepts is given. The nursing theory, Modeling and Role-Modeling, is presented as an example of a theoretical perspective that encompasses the holistic orientation. Case examples of how this theory has been used in clinical practice are offered. PMID- 2325535 TI - QUALITY: quantification improvement by converting lineshapes to the Lorentzian type. AB - A method of time domain deconvolution, QUALITY, is described for general use in quantitative NMR spectroscopy. By division of the experimental NMR time domain signal by a reference signal, which may be obtained either in a separate experiment or via inverse Fourier transformation of an isolated single resonance in the experimental spectrum, perfect Lorentzian lineshapes can be obtained regardless of the magnetic field inhomogeneity. Experiments, both in vivo using a surface coil and in vitro using a surface coil and a HR NMR probe, show excellent performance of the method. PMID- 2325537 TI - Efficient remote transmission line probe tuning. AB - An approach is described which allows remote tuning of a probe via a length of transmission line, while retaining nearly ideal efficiency relative to the equivalent locally tuned coil. This preservation of efficiency is accomplished through the principle of "partial local matching." In comparison to common methods of remote tuning which involve half-wavelength cables, or in which a length of transmission line is itself utilized as a tuning element, the partial matching method results in a substantial increase in the efficiency of power transfer to the coil, and therefore increased B1 field intensity and signal-to noise ratio. Applications in which the use of local variable tuning capacitors is made difficult by either space, accessibility, or environmental considerations should benefit from this method. PMID- 2325536 TI - In vivo 19F spin relaxation in index finger bones. AB - 19F free induction decay (FID) signals have been observed from the index fingers of four male and two female adult volunteers using a 27-MHz pulsed nuclear magnetic resonance spectrometer equipped with a split ring resonator probe. The value of the in vivo spin-lattice relaxation time T1 of the fluoride ions naturally accumulated in bone mineral has been determined to be 2.0 +/- 0.3 s. The shape of the observed FID signals in the inhomogeneous external magnetic field indicates that the F distribution is not uniform along the length of the finger. The fluoride ion content of the index finger (within a 65-mm length from its distal end) was measured with a sensitivity of +/- 0.5 mg F within a 30-min observation time. PMID- 2325538 TI - A continuously variable field of view surface coil. AB - A new type of surface coil is described which allows the user to continuously vary the size of the field of view. This utilizes a modified radiofrequency trombone for size adjustment that results in a stable frequency over a wide range of dimensions. Results show that the coil may be increased in area by as much as 60% while maintaining frequency stability to ca. 1 MHz at 63.5 MHz. Images of the human spine are presented to demonstrate the clinical utility of the new design. PMID- 2325539 TI - Switched array coils. AB - Switched array coils (SACs) are a useful tool in local coil imaging since they allow in a user-friendly manner one to make the best choice in the trade-off between field of view and signal-to-noise ratio. This is done by selecting the current path within a conductor array equipped with suitable switches. Since the switching can be controlled by the system, this allows changing of the coil dimensions within multislice sequences. Thus image quality can be improved due to smaller coil dimensions for a given slice and a larger area can be covered by electronically shifting this sensitive area. The principle can be applied to surface--as well as volume--coil designs. PMID- 2325540 TI - Spin-lattice relaxation time measurements using hybrid CSI--phantom study. AB - The spin-lattice relaxation time T1 of multicomponent tissues is often determined by fitting relaxation data to monoexponential functions. This process can lead to large errors in the relaxation time. We describe a procedure using chemical-shift imaging (CSI) which separates the NMR signal into water and lipid components thus allowing the two signals to be individually analyzed for relaxation times. This procedure yields more representative relaxation times than those obtained by both monoexponential and biexponential fitting schemes. PMID- 2325541 TI - Quantitation of abdominal aortic wall dynamics in man by gradient echo NMR imaging. AB - To determine the magnitude of the pulsatile (P), translational (T), and composite (C) aortic wall motion and to predict its effect on endothelial edge definition in vascular NMR imaging, 10 healthy volunteers, mean age 42.5 +/- 13 years, were studied. In each subject a series of transverse high-resolution (0.6 X 0.6 mm; TR = 40 ms) gradient echo images spanning the cardiac cycle were generated and the aortic wall motion dynamics were analyzed. The group data expressed as a mean +/- SD in millimeters, P = 0.87 +/- 0.34 (mm), T = 2.71 +/- 1.07, and C = 3.39 +/- 1.081, indicate that a significant displacement of the endothelial aortic edge (up to 5.6 pixels in high-resolution imaging) occurs during the cardiac cycle in normotensive healthy volunteers. The displacement of this magnitude suggests that cardiac cycle synchronized aortic NMR imaging should be used to improve endothelial edge definition. PMID- 2325542 TI - In situ assessment of tumor vascularity using fluorine NMR imaging. AB - In situ fluorine NMR imaging has been used to measure vascularity in subcutaneously implanted mammary tumors. Oxyferol, a perfluorinated blood substitute comprised of an emulsion of 25% w/v perfluorotributylamine, was used as a tracer. Following iv administration, this perfluorocarbon emulsion remains primarily in the vasculature during the image acquisition period. The distribution of the PFTA in the 19F NMR image gives a map of tissue regions with intact vascularity. This technique has been used to demonstrate decreased blood flow in necrotic regions of R3230AC mammary tumors in which vasculature had been damaged either as a result of spontaneous necrosis or by photodynamic therapy (PDT). Damage to tumor vascularity following PDT was observed prior to the development of necrosis. PMID- 2325543 TI - Assessment of a superparamagnetic iron oxide (AMI-25) as a brain contrast agent. AB - We have applied a superparamagnetic iron oxide formulation (AMI-25, Advanced Magnetics, Inc., Cambridge, MA) to image the cerebral vasculature. Contrast enhanced images of normal anesthetized rats demonstrated excellent gray/white matter differentiation, consistent with known differences in blood perfusion, and cerebrospinal fluid spaces were clearly seen. Alterations in normal perfusion patterns due to barbiturate anesthesia and ischemia were clearly visible. We propose the use of this agent as an adjunct to MRI for the imaging of conditions with perfusion abnormalities. PMID- 2325544 TI - A simple calf muscle ergometer for use in a standard whole-body MR scanner. AB - A calf muscle ergometer, designed for use in a standard whole-body MR scanner, is described. The instrument allows isotonic or isometric calf muscle exercise over a continuous range of work loads from 0 to individual maximum work output. Work output may be recorded on a strip chart recorder. A sound encoding provides an effective guidance for the subject tested to accurately reproduce his performance in each contraction cycle at a given work load. The FID recording may be triggered from the ergometer at any point during the contraction cycle. Nonmetal materials are used for the instrument construction in order to eliminate potentially disturbing eddy currents. The force resistance of the ergometer is obtained by a combined hydraulic-pneumatic system, which is loaded by coupling to an outside source of compressed air equipped with a suitable pressure regulator. When varying the time of data sampling within a repeated 6-s contraction cycle it was found that the recorded Pi/PCr ratio remained essentially constant at low and moderate work loads. However, at work loads at or above 70% of individual Vmax a pronounced dependence of the time of sampling with the contraction cycle was observed. PMID- 2325545 TI - Heterotopic transplanted rat heart: a model for in vivo determination of phosphorus metabolites during ischemia and reperfusion. AB - A model of heterotopic isogenic rat heart transplantation was developed in order to noninvasively observe the acute and chronic metabolic changes of ischemia. This study presents the results of 31P spectroscopy during acute global ischemia and reperfusion. The advantages of this model over other surface coil in vivo ischemia experiments are: (1) Thoracotomy for surface coil positioning is not required, thus the results are not influenced by the effect of recent major surgery. (2) Survival is not influenced by the degree of ischemic damage to the transplant, and the model enables repeated long-term studies of the metabolic effect of reversible ischemia, and myocardial infarction. (3) The pathologic process created is homogeneous and thus the results are not complicated by variation in the severity of myocardial ischemia. PMID- 2325546 TI - The use of laboratory microcomputers to hold NMR data bases. AB - Computer-based data bases are essential tools for NMR spectroscopists working with complex mixtures such as tissue extracts. Algorithms are described which are easily implemented on a small laboratory microcomputer and which can be used to make, edit, and query personalized laboratory data files. The data are stored in a series of small files accessed by pointers to overcome inherent redundancy in the information. Performance times are tabulated for a BBC Model B microcomputer working in the BASIC language and using 5.25-in. floppy discs as virtual memory. PMID- 2325547 TI - In vivo NMR diffusion spectroscopy: 31P application to phosphorus metabolites in muscle. AB - Apparent diffusion coefficients (Da) of individual metabolites can be studied in vivo by diffusion NMR spectroscopy using an echo sequence sensitized to molecular motion. The methods are based on the echo attenuation due to phase dispersion resulting from incoherent displacement during the diffusion time. As the displacement of metabolites by diffusion in vivo can be affected by compartment size, temperature, adsorption processes, etc., the presented methods are potentially useful in studying such phenomena in vivo. Here, the methods are applied to phosphocreatine in the rat quadriceps muscle. It is demonstrated that the displacement of phosphocreatine resembles free diffusion for short diffusion times but becomes limited as a result of boundaries due to compartmentation for longer diffusion times. The limit of the displacement indicates an apparent average size of 44 microns of the compartment in the direction of the diffusion gradient. As the gradient was applied approximately parallel (angle less than 25 degrees) to the muscle fiber, this result indicates that phosphocreatine moves freely in the cytosol but is limited by the boundaries of the muscle cells. Error analyses are performed with regard to motion artifacts and gradient performance. The methods were tested extensively for distilled water and free metabolites. PMID- 2325548 TI - Hydrogen/fluorine retuning tomography. Applications to 1H image-guided volume selective 19F spectroscopy and relaxometry of perfluorocarbon emulsions in tissue. AB - A hardware modification which permits the record of 19F images, spectra, and relaxation times with a 1H tomography bird-cager resonator is described. Changing the spectrometer frequency from 1H to 19F resonance and vice versa is possible without removing the object to be investigated. This hydrogen/fluorine retuning tomography (HYFY) technique permits studies of identical slices or volume elements with 1H as well as with 19F resonance. In particular, it is possible to localize volume elements on the basis of multislice proton images and then to investigate these volume elements with fluorine magnetic resonance by the aid of volume selection methods. For this purpose, pulse sequences for the localized and spectroscopically resolved determination of spin-lattice and transverse relaxation times have been developed. The applicability of the techniques has been demonstrated by the aid of phantom samples as well as with excised porcine organs which have been perfused with perfluorocarbon emulsions. PMID- 2325549 TI - NMR spectral analysis of kinetic data using natural lineshapes. AB - An automated rapid data analysis scheme for NMR spectroscopy time course studies is presented. This method uses a high signal-to-noise reference spectrum collected at the beginning of a time course as a lineshape model to analyze subsequent low signal-to-noise data collected with higher time resolution. The method is fast (approximately 1 s to evaluate two peaks in a 2K spectrum) and easily implemented on NMR spectrometer computers. An application of this method to spectroscopic studies on the heart is provided. PMID- 2325550 TI - Multinuclear NMR investigations of probe construction materials at 4.7 T. AB - Since background signal from NMR probes can overwhelm the signal from a sample, the NMR analysis of plastics or machinable ceramics is a prerequisite to their use in probe implementations. The contributions from a variety of materials to proton, fluorine, and carbon NMR spectra are presented. PMID- 2325551 TI - Assessment of intracellular magnesium depletion in rat striated muscle by in vivo 31P NMR. AB - Previous in vivo studies have demonstrated that alpha, beta, and gamma ATP chemical shifts measured by 31P NMR spectroscopy can be used to determine intracellular magnesium in erythrocytes, but up to now such results have not been confirmed in striated muscle in vivo. We report beta ATP chemical-shift in vivo measurements revealing the depletion of free intracellular magnesium in striated muscle of rats fed a magnesium deficient diet. PMID- 2325552 TI - 1H NMR observation of tissue myoglobin: an indicator of cellular oxygenation in vivo. AB - Cellular oxygen status is a critical parameter. To measure the oxygen tension in vivo, however, demands extant techniques to surmount two experimental difficulties: invasive experimental protocols and imprecise tissue localization. NMR techniques have the potential to overcome these obstacles. Indeed we show in this study that cellular myoglobin is NMR visible and its proximal histidyl NH signal in the deoxy state can be used to monitor changes in cellular oxygenation. Coupled with recent advances in NMR signal localization, this 1H NMR strategy promises to lead directly to cellular oxygen measurement in specific tissue regions in vivo. PMID- 2325553 TI - A survey of microsurgery training in the United States. AB - The increasing use of clinical and experimental microsurgical techniques has created a need for standardized, high-quality training programs in microsurgery. Toward this end, we conducted a study of the microsurgery instruction available in the United States. The data were collected from responses to surveys mailed to 55 microsurgery training centers across the country. Survey questions asked for a general characterization of each training program and its participants and for a specific description of course content. The results indicated that, even though training programs differed considerably, there were common elements. Total course length ranged from less than 40 hours to 80 hours, with a range of 32-40 hours devoted to basic microsurgery techniques. Forty percent of instructional programs were not certified for continuing medical education (CME) credit. Half of all reported trainees were residents in training. The basic microsurgery techniques common to most programs included instruction in microvascular end-to-end and end to-side anastomoses of femoral arteries and veins in rats. Instruction in peripheral nerve repair was not offered. We conclude that, although there are merits to a diverse curriculum, it is time to institute a minimum level of standardized basic microsurgery training. PMID- 2325554 TI - Morphological studies of cellular responses to experimental arterial grafts. AB - Cross-carotid microvascular bypass grafts 2-3 mm in diameter were implanted using microsurgical techniques for end-to-end anastomosis in four dogs. One autograft control and one of three denatured human umbilical artery xenografts (HUAG) were patent at 5 weeks. One of the other two denatured HUAGs had thrombosed at 1 week, and the other was occluded at 5 weeks. Host and graft vessel specimens were evaluated histologically as well as with transmission electron microscopy after sacrifice. Results indicate that failure of reconstitution of a true endothelial layer, presence of a subintimal myofibroblast population, increased collagen deposition of the muscularis, and occlusion of the adventitial and mural microcirculation were observed in both the early and late nonpatent vessels but not in the patent specimens. Evidence for myointimal cell proliferation was present in both patent and occluded grafts. A cohesive intimal layer was observed in both patent cases. Microvascular occlusion, due to an excess of endothelial cells, of new vasa vasorum in one case seems related to increased fibrosis, which could have resulted in graft stenosis. The surgical procedures and subsequent morphological analyses were adequate and sufficient for use in a long-term study of the possible causes of graft failure. PMID- 2325555 TI - Wound healing at the site of microvascular anastomosis: fibrin-stabilizing factor XIII administration and its effects. AB - Factor XIII has recently been recognized to play an important role as a fibrin stabilizing factor to accelerate the wound healing process. We made an attempt to analyze the effect of how Factor XIII affects the results of the healing process at the site of a microvascular anastomosis. The strong fibrin stabilizing property of plasma Factor XIII maintained its high activity when administered intravenously and was effective for wound healing in a low-activity state made by subcutaneous administration of carbon tetrachloride. The enhanced network formation of the Factor-XIII-injected group was indicated by the accelerated maturation of the fibrin structure at the anastomotic site, exhibited both qualitatively and quantitatively. Stimulation and acceleration by Factor XIII of the healing process at the site of microvascular anastomosis were observed. It is therefore suggested that clinical use of Factor XIII may enhance the microvascular repair process. Details of the analysis using scanning electron microscopy (SEM) and a computerized graphic analyzer system (CGAS) are reported. PMID- 2325556 TI - Indications for complex skin coverage in the lower limb. PMID- 2325557 TI - Technical successes and functional failures after free tissue transfer to the tibia. AB - A retrospective study evaluated functional outcome in 59 patients with 61 successful free tissue transfers performed after open tibial fractures. Twenty one patients had transfers done within 7 days, 13 between 7 and 21 days, and 25 were done greater than 3 weeks after injury. All 59 patients had Type III injuries as classified by Gustilo and Anderson. Nineteen patients (32%) were identified as late functional failures. Each of these patients underwent as average of 10 procedures. In this group chronic osteomyelitis was noted in 13 of 19 patients and chronic venous insufficiency with skin ulceration in 9 of 19 patients. Fracture nonunion was seen in 8 of 19. Degenerative joint problems and foot deformities were identified in 7 or 19 patients. Seven patients (12%) ultimately required below-knee amputation. Functional failure did not correlate with the timing of flap application, but rather with the severity of the initial injury. Free tissue transfer is not a panacea. It is but one step in the overall reconstruction of complex tibial wounds. PMID- 2325558 TI - Femoral reconstruction by vascularized bone transfer. AB - Thirty-five patients with extensive femoral defects or recalcitrant nonunions were reconstructed by microvascular bone transfer with a follow-up period exceeding 12 months. The cause of bone defect included trauma, debridement for osteomyelitis, or tumor resection, and the cause of nonunion included trauma or postirradiation osteonecrosis. Sixty-nine percent of patients healed primarily, whereas 83% of patients ultimately progressed to union following secondary surgery. One patient who initially healed later required amputation for late graft fracture with nonunion; therefore, at final follow-up, 80% of patients were fully healed. Vascularized bone transfer merits strong consideration for reconstruction of atypical and particularly difficult femoral nonunions. PMID- 2325559 TI - Effects of acute smoking and exercise on high-density lipoprotein-cholesterol and subfractions in black female smokers. AB - This study investigated the effects of acute bouts of both exercise and smoking on high-density lipoprotein-cholesterol subfractions, HDL2-C and HDL3-C in black females. During two testing trials, seven subjects were exposed to either acute exercise or smoking. Treadmill exercise was performed at 70% of heart rate reserve for 15 minutes. Blood samples were taken before, immediately after, and 10 minutes after exercise. The smoking trial consisted of subjects smoking two cigarettes followed by 30 minutes of nonsmoking. Blood samples were taken before smoking, after each cigarette, and after two 15-minute intervals of nonsmoking. The exercise protocol resulted in a 10.8% increase in total HDL-C, primarily through an increase in the HDL2-C subfraction. The values returned to baseline within 10 minutes after exercise. Smoking one cigarette decreased total HDL-C by 10%. Neither subfraction was significantly effected by smoking; however, the HDL3 C subfraction was decreased 11% and HDL2-C subfraction was decreased 14.7% from resting values. The maximum reduction in HDL3-C subfraction occurred after the smoking of the first cigarette, while the maximum reduction in the HDL2-C subfraction occurred after the first 15-minute nonsmoking period. Acute cigarette smoking was associated with a decrease in total HDL-C that was maintained through 15 minutes of nonsmoking. It is suggested that the adverse effect on HDL-C by acute smoking is a significant contributor to coronary heart disease (CHD) risk in black females. Results further indicate that low-intensity exercise is capable of transiently increasing the total HDL-C via an increase in the anti-atherogenic HDL2-C subfraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325560 TI - Postprandial plasma vitamin A metabolism in humans: a reassessment of the use of plasma retinyl esters as markers for intestinally derived chylomicrons and their remnants. AB - We investigated postprandial vitamin A metabolism by measuring retinyl ester, triglyceride, and apolipoprotein (apo)B-48 in the plasma lipoproteins of human subjects before and after fat-feeding. Following a 14-hour fast, eight healthy subjects (two men, six women, 28 to 79 years) were given a fat-rich meal (1 g fat/kg body weight) containing vitamin A (40 retinol equivalents per kilogram body weight). Blood was collected every 3 hours for 12 hours and lipoproteins were isolated by sequential ultracentrifugation. Mean plasma retinyl ester concentration peaked 6 hours after the fat-rich meal, whereas mean plasma triglyceride peaked at 3 hours. Data obtained from hourly samples in 3 subjects showed that changes in the postprandial plasma concentration of retinyl ester occurred 1 to 2 hours after changes in the plasma triglyceride concentration. In triglyceride-rich lipoproteins (TRL) of d less than 1.006 g/mL, retinyl ester similarly peaked at 6 hours, whereas triglyceride as well as apoB-48 peaked at 3 hours. Although retinyl esters were found mainly in TRL in the initial postprandial period (84%, 3 hours; 83%, 6 hours), in fasting and postprandial plasma, particularly 9 or more hours after fat-feeding, a large percentage of plasma retinyl esters were in low-density lipoproteins (LDL) (44%, fasting; 9%, 3 hours; 9%, 6 hours; 19%, 9 hours; 32%, 12 hours). A small percentage of retinyl esters were also found in postprandial high-density lipoproteins (HDL) (2% to 7%). ApoB-48 was not detected in LDL of fasting or postprandial plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325561 TI - The effects of chronic fish oil feeding in rats on protein catabolism induced by recombinant mediators. AB - The influence of dietary lipid manipulation with menhaden or safflower oil on changes in protein metabolism in rats receiving recombinant interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha/cachectin (TNF), or both combined (COINF) was examined. Whole-body protein kinetics, energy expenditure, nitrogen excretion, and liver and muscle protein synthesis were studied using tracer quantities of L-[1-14C]-leucine. Rats fed menhaden oil, high in omega-3 fatty acids, had significantly lower rates of leucine oxidation compared to safflower fed rats after monokine infusion (P less than .05). However, muscle protein synthetic rates and the specific activity of free leucine in plasma and muscle indicated greater net muscle-protein breakdown in animals fed fish oil or receiving monokines. Rats fed omega-3 fatty acids had significantly larger livers as percent of body weight and more total liver protein than safflower oil controls (P less than .0001). Liver weight was further increased by monokines, particularly TNF and COINF (P less than .001) in both diet groups, suggesting that net hepatic anabolism occurred at the expense of net skeletal protein catabolism. Monokines as a group and COINF significantly decreased whole-body leucine flux and incorporation into protein; no effect of menhaden oil was noted. In addition, monokines increased nitrogen excretion during the 24-hour experimental period (P less than .05), and total energy expenditure rose significantly in all groups receiving IL-1 beta and COINF. The recombinant monokines IL-1 beta and TNF, particularly when coinfused, are able to reproduce many of the protein anabolic and catabolic consequences seen following infection and injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325563 TI - Clinical update on calcitriol: introduction. PMID- 2325562 TI - Decreased cholesterol biosynthesis in sitosterolemia with xanthomatosis: diminished mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and enzyme protein associated with increased low-density lipoprotein receptor function. AB - We investigated the mechanism for reduced cholesterol biosynthesis in sitosterolemia with xanthomatosis. The conversion of acetate to cholesterol and total and active hydroxymethylglutaryl (HMG) coenzyme A (CoA) reductase activities, enzyme protein mass, and catalytic efficiency were related to low density lipoprotein (LDL) receptor function in freshly isolated mononuclear leukocytes collected at 9 AM after a 12-hour fast from two affected sisters and 12 control subjects. Active HMG-CoA reductase activity was determined in mononuclear leukocyte microsomes prepared and assayed in the presence of sodium fluoride, while total HMG-CoA reductase activity was determined in the absence of the phosphatase inhibitor. Enzyme protein was assayed using rabbit polyclonal anti-rat liver microsomal HMG-CoA reductase serum. The rates at which [14C]acetate was transformed to cholesterol by sitosterolemic mononuclear leukocytes were decreased 29% and 41%, respectively, compared with the mean value for mononuclear leukocytes from 12 control subjects. Similarly, total HMG-CoA reductase activities were 71% and 68% lower in sitosterolemic mononuclear leukocyte microsomes and were associated with 62% and 65% less enzyme protein than the mean for the control microsomal preparations. This marked decrease in HMG-CoA reductase protein mass in sitosterolemic microsomes was partially compensated for by an increase in the proportion of active enzyme. Sitosterolemic plasma and mononuclear leukocyte cholesterol concentrations were not significantly different from control values, although total sterol levels were increased about 20% because of abundant plant sterols. In contrast, receptor mediated LDL degradation by sitosterolemic mononuclear leukocytes was increased 50% over control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325564 TI - Clinical update on calcitriol. A symposium. Seattle, WA, June 2, 1989. Proceedings. PMID- 2325565 TI - Role of 1,25(OH)2D in the genesis of secondary hyperparathyroidism of early renal failure and its use in the prevention of this abnormality. AB - To clarify the mechanisms of hypocalcemia with renal insufficiency and to gain more insight into the mechanisms of secondary hyperparathyroidism in these patients, an 85-day study was conducted to examine the effect of dietary phosphate restriction on divalent ion metabolism in patients with early renal insufficiency. The study was conducted on four male patients with stable mild renal insufficiency who had creatinine clearances of 55 to 60 mL/min. Our results correspond with those of other studies that indicate that phosphate restriction is adequate to reverse and correct secondary hyperparathyroidism as well as other abnormalities in divalent ion metabolism. Because dietary phosphate restriction appears to exert its effect through the increased production of 1,25(OH)2D, an alternative therapeutic approach would be supplementation of 1,25(OH)2D3 (calcitriol). To test this, another study was conducted evaluating the effect of 1-year therapy with 1,25(OH)2D3 on blood levels of parathyroid hormone (PTH) and on various parameters of bone pathology in patients with creatinine clearances of 15 to 55 mL/min. Our results showed that the use of calcitriol is safe and effective in the management of secondary hyperparathyroidism and bone disease in patients with moderate renal failure. PMID- 2325566 TI - Role of calcitriol in prevention of osteoporosis: Part I. AB - Prevention of postmenopausal osteoporosis is an alternative to the currently problematic goal of reversing the trabecular plate thinning and perforation that constitute the major pathologic defects in patients with established osteoporosis. 1,25(OH)2D3 (calcitriol) has been suggested as a drug that may decrease bone resorption sufficiently to preserve trabecular structure in perimenopausal women. In the present study, we compared the effects of calcitriol and an investigational analog, 1,25,26-(OH)3delta22-D3 (Ro-23-8525), to those of an inert vehicle in maintaining the bone mass of oophorectomized adult beagles. In these studies, we used dual-energy radiography to serially quantitate the bone density of control and treated animals. Treatment for 1 year with either agent resulted in no evidence of hypercalcemia or decreased renal function. Moreover, calcitriol and Ro-23-8525 effectively abolished the loss of bone mass observed in untreated oophorectomized controls. Indeed, treated animals displayed variations in bone density similar to that observed in sham-operated untreated animals. These data suggest that calcitriol and Ro-23-8525 may be potentially effective agents for prophylaxis of postmenopausal osteoporosis. PMID- 2325567 TI - Role of calcitriol in the management of osteoporosis. AB - Ovariohysterectomized Beagle dogs provide a useful model for the study of bone loss following cessation of ovarian function. Data obtained in our laboratory suggest that the sequence of events occurring after cessation of such function proceeds in two phases. The first, or "initiation," phase begins within 1 month after ovariohysterectomy (OHX). Although the number of osteoclasts is unchanged, there is an increase in trabecular separation, accompanied by a dramatic decrease in cancellous bone volume, which suggests an apparent dramatic hyperresorption. This early phase is followed by a "maintenance" phase, which commences in the second month and is related to an osteoblastic insufficiency. In another experiment, administration of 1,25(OH)2D3 corrected bone loss occurring after OHX in Beagle dogs. However, a positive balance between increased bone cell activity and decreased bone cell number was not maintained. This calls for new strategies to separate the positive effect of 1,25(OH)2D3 on bone cell activity from the negative effect on bone cell number. PMID- 2325568 TI - Metabolic effects of synthetic calcitriol (Rocaltrol) in the treatment of postmenopausal osteoporosis. AB - The long-term safety and efficacy of synthetic 1,25-(OH)2D3 (calcitriol; Rocaltrol) in the treatment of women with type 1 osteoporosis is being assessed in a randomized trial. Patients were allocated in double-blind fashion to 1,25 (OH)2D3 or matching placebo. Initially, the calcium intake was adjusted to 1,000 mg/d. The study protocol called for increasing the dose of 1,25-(OH)2D3 until patients developed either hypercalcemia or hypercalciuria. However, in order to maintain a higher dose of calcitriol on a long-term basis, the calcium intake had to be reduced to 600 mg/d in those receiving calcitriol; if that was not successful in eliminating hypercalcemia and hypercalciuria, then the dose of 1,25 (OH)2D3 was reduced as necessary. During the hypercalcemic phase, the indices of bone resorption decreased significantly, demonstrating that calcium absorption is solely responsible for hypercalcemia. The maintenance dose was established after 8 to 10 weeks, and the 24-hour urine calcium and creatinine clearance remained constant throughout the remainder of the study period. On a calcium intake of 600 mg/d, the long-term maintenance dose of 1,25-(OH)2D3 averaged 0.675 micrograms/d. Long-term therapy on an average dose of 0.675 micrograms/d was not associated with nephrotoxicity. PMID- 2325569 TI - Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate. AB - In postmenopausal osteoporotics, malabsorption of calcium is associated with reduced levels of serum 1,25-dihydroxyvitamin D. Metabolic studies have shown that calcium absorption can be normalized and calcium balance improved after administration of oral doses of synthetic 1,25-dihydroxyvitamin D3 (Rocaltrol) 0.25 micrograms twice daily. Further studies performed at two centers compared the effect of Rocaltrol 0.25 micrograms twice daily versus placebo on vertebral fracture rates in osteoporotics. A significant reduction in vertebral fracture rates was seen at the end of 1 year. Those patients who continued on Rocaltrol for a second and third year showed a progressive decrease in vertebral fractures. Rocaltrol, administered at a dose of 0.25 micrograms twice daily, seldom causes hypercalcuria or hypercalcemia in osteoporotic patients on a typical calcium intake of 700 to 800 mg/d. Careful measurements of renal function over a period of 3 years in patients treated with Rocaltrol, 0.25 micrograms twice daily, showed no deterioration in renal function. These data suggest that 1,25 dihydroxyvitamin D3 is a useful therapy in the management of patients with postmenopausal osteoporosis, particularly those who have malabsorption of calcium. We found that it improves calcium balance, reduces the vertebral fracture rate, and is safe to use provided that the dietary calcium is monitored and does not exceed 800 mg/d. PMID- 2325570 TI - Studies of osteoporosis in Japan. AB - Calcium deficiency appears to play a central role in the development of involutional osteoporosis, especially in Japan, where calcium intake has been traditionally low, never reaching the current recommended daily allowance (RDA) of 600 mg/d. Compromised 1,25(OH)2 vitamin D synthesis in the aging kidney and age-bound changes of the intestine itself lead to calcium malabsorption; in addition, decreasing dietary intake of fat-soluble vitamins and reduced solar exposure associated with inadequate physical activity may contribute to calcium deficiency in old age. High salt intake and increasing protein and phosphate intake tend to aggravate such a tendency. These factors appear to underlie, in part, the widespread use of vitamin D derivatives for the treatment of osteoporosis in Japan. In 1981, a large-scale, double-blind clinical trial established the superior effect of 1 alpha(OH) vitamin D3 in maintaining bone density over that of placebo. The effect of 0.5 micrograms/d 1,25-(OH)2D3 (calcitriol) in two divided doses compared favorably with that of 1 micrograms/d of 1 alpha(OH) vitamin D3 in a recently conducted multicenter, double-blind study on 596 patients with involutional osteoporosis. Spinal fracture rate was also reduced to one-half by administration of the vitamin D derivative for 1 year to 800 patients with osteoporosis. PMID- 2325571 TI - Long-term treatment with calcitriol in postmenopausal osteoporosis. AB - In order to assess the long-term effects of calcitriol treatment in postmenopausal osteoporotic patients, 1.0 micrograms/d of calcitriol was administered in two divided doses for 1 to 8 years to 270 women with symptomatic, histologically proven postmenopausal osteoporosis. No calcium supplementation was given. Clinically, the treatment resulted in substantial relief from pain, with improvement of ambulancy. Intestinal calcium absorption, which was lower than normal at baseline, increased significantly and remained higher than the baseline value as long as calcitriol was administered. Urinary calcium absorption also increased, but hypercalcemia occurred, exceptionally and transiently, in only a few patients. Urinary hydroxyproline excretion did not increase, indicating that hypercalciuria was not of resorptive origin. Total-body density, determined by dual-photon total-body absorptiometry in 56 patients, showed an increase after 18 to 24 months of therapy in most cases. The occurrence of nontraumatic, clinically relevant fractures decreased noticeably as compared with the period preceding calcitriol treatment. No change occurred in renal function, and no renal stones developed. Calcitriol was an effective and safe treatment of postmenopausal osteoporosis. PMID- 2325572 TI - Low-dose calcitriol versus calcium in established postmenopausal osteoporosis. AB - An ongoing randomized clinical trial of 3 years duration is being undertaken to evaluate the recurrent fracture rate and safety profile associated with low-dose calcitriol versus calcium supplementation in women with at least 3 years postmenopausal osteoporosis who are under the age of 80 years. A total of 856 patients were submitted for possible inclusion in the study by 123 primary care physicians, and 636 met all entry requirements. Each patient was randomly allocated to receive either 0.25 micrograms of calcitriol twice daily or calcium supplementation of 1,000 mg/d. If significant hypercalcemia developed (greater than 2.6 mmol/L) or a deterioration in renal function was observed, the dose of trial medication was to be halved or stopped if laboratory values did not return to normal. Patients were given no specific instructions regarding dietary calcium intake. To date, 528 patient-years experience with calcitriol and 527 patient years experience with calcium the calcium supplementation have been accumulated. Thus far, low-dose calcitriol has not been observed to cause hypercalcemia, deterioration in renal function, or nephrocalcinosis. At 1 year, a loss in total anterior height (P less than .05) has been detected in the calcium-treated group compared with the calcitriol-treated group. Thus, calcitriol appears to preserve spinal height. Long-term follow-up of all patients for 2 or 3 years will be continued. PMID- 2325573 TI - Calcium and calcitriol therapy in osteoporotic postmenopausal women with impaired calcium absorption. AB - The effects of oral calcitriol (0.25 and 0.50 micrograms/d), together with calcium (1 g/d), on calcium absorption and bone resorption were measured in postmenopausal osteoporotic women with calcium malabsorption. Radiocalcium absorption was significantly improved and urinary hydroxyproline/creatinine excretion significantly reduced on both doses, but the higher dose caused an unacceptable incidence of hypercalcemia. In 49 patients treated for an average of 15 months with the lower dose, there was a nonsignificant gain in forearm bone mass of 0.4 +/- 0.3 mg/cm/mo (approximately 1/2% per annum) compared with a significant decrease in 17 untreated patients of 3.8 +/- 1.3 mg/cm/mo (approximately 5% per annum). PMID- 2325574 TI - Choices in childbirth. PMID- 2325575 TI - Is it important or even useful to measure weight gain in pregnancy? PMID- 2325576 TI - HIV infection and community midwives: experience and practice. AB - To assess the effects of HIV infection on the work of community midwives, a postal survey of 1 in 5 in Scotland and England was carried out. The 907 respondents represent an 83% response rate. While only 1% of respondents had experience of patients with AIDS, 8% had been involved with known asymptomatic HIV infection and 32% had encountered those that they considered to be 'at high risk'. While the workload generated by HIV-infected patients for individual midwives at this time was small, almost all midwives themselves considered that they had a role to play in the prevention of HIV infection through health education and in counselling. While less than a quarter of those who had encountered HIV-positive patients had provided health education, more than half had done so to those worried about HIV infection and almost a quarter had counselled them. However, confidence to provide these aspects of practice was low, even among those who had received in-service education, although higher than among those who had not done so. A minority of community midwives had read policies or guidelines about aspects of practice and service provision, except for infection control where two thirds had read what they considered an adequate policy. PMID- 2325577 TI - Morphological detection of filipin-sterol complexes in the cytoplasmic membrane of staphylococcal L-form. AB - Filipin, a sterol-specific antibiotic, and freeze-fracture electron microscopy were used to study the presence and distribution of sterol in the cytoplasmic membrane of stable staphylococcal L-form cells. Fixed cells were treated with filipin, and then observed by freeze-fracture electron microscopy. Freeze fractured profiles of the L-form cells treated with filipin demonstrated irregular distribution of protuberances or pits of 25-30 nm, representing filipin sterol complexes, on the proto-plasmic fracture face (PF) and exoplasmic fracture face (EF) of the cytoplasmic membrane. In contrast, no such structure was detected in the filipin-treated parent cells or protoplasts. The results suggest that some sterol molecules, which are usually not found in staphylococcal or other bacterial cells, emerged on the cytoplasmic membrane after the cells were converted to the stable L-form. PMID- 2325578 TI - Granuloma-forming activity and antitumor activity of newly isolated mycoloyl glycolipid from Rhodococcus terrae 70012 (Rt. GM-2). AB - A newly isolated mycoloyl glycolipid (Rt. GM-2) from Rhodococcus terrae 70012 was identified and the granulomagenic and antitumor activities were studied as compared with trehalose-6,6'-dimycolate (cord factor) also from R. terrae (Rt. TDM). The alkaline hydrolysis products of Rt. GM-2 contained trehalose, methyl alpha-mycolate and a less-polar ester than the usual methyl-alpha-mycolate, possibly beta-keto mycolate (1:1:1, by mol. ratios). On the other hand, analysis of alditol acetate obtained after the mild permethylation, NaBH4 reduction, and acetylation showed the occurrence of 2,3,4-tri-O-methyl-6-O-acetylglucitol. Therefore, the original glycolipid (Rt. GM-2) was identified tentatively as 6-O alpha-mycoloyl 6'-O-beta-ketomycoloyl trehalose. Intravenous injection of Rt. GM 2 in the form of water-in-oil-in-water emulsion caused prominent granulomas in lungs and spleen of ICR and BALB/c mice. The granulomagenic effects were as strong as those caused by Rt. TDM. The lung and spleen weights reached peaks one week after an injection of Rt. GM-2 in mice and then gradually decreased. Multiple intravenous injections of Rt. GM-2 and Rt. TDM showed antitumor activity against subcutaneously implanted Sarcoma-180, and caused prominent granulomatous changes and growth suppression of mice. PMID- 2325579 TI - Demonstration of a surface antigen of Clostridium tyrobutyricum by use of immunoblotting with a monoclonal antibody. AB - A monoclonal antibody, prepared against whole cells of Clostridium tyrobutyricum, recognized a surface antigen extracted by heat treatment or by hot phenol-water treatment. This antigen, after analysis by polyacrylamide gel electrophoresis and immunoblotting, has been shown to present a regularly-spaced ladder pattern similar to those shown by the lipopolysaccharide of many gram-negative bacteria. The proteinase K has been shown to have no effect on the recognition of this epitope by the monoclonal antibody. On the contrary, the inhibition of the antigen reactivity to the monoclonal antibody after a mild periodate oxidation suggests the involvement of a carbohydrate moiety in the epitope. Moreover, the SDS-PAGE analysis of phenol-water extracts has shown an additional compound, detected by silver staining but not recognized by the monoclonal antibody. PMID- 2325580 TI - Cell surface of a tetrads-forming mutant of Micrococcus luteus: chemical treatment of the cells and teichuronic acids on the surface. AB - Tetrads-forming mutant MT cells of Micrococcus luteus, both treated with chemical reagents and non-treated, were observed with a scanning electron microscope (SEM). The agglutinability of the cells with antiserum containing anti teichuronic acid antibody was examined. The binding of protein A-gold particles to the cells, mediated with the antiserum, was also observed with SEM. A tetrad surface, not surface of each of four "unit monococci" constituting a tetrad, consisted of two or three smooth areas with borders. The difference in the surface features between M. luteus wild-type IFO 3333 (Monodane et al, Microbiol. Immunol. 33: 165-174, 1989) and the mutant MT cells is discussed. PMID- 2325581 TI - Genotypic and phenotypic differentiation of Flavobacterium indologenes Yabuuchi et al 1983 from Flavobacterium gleum Holmes et al 1984. AB - The type and eight strains of Flavobacterium indologenes were clearly differentiated from the type and two reference strains of Flavobacterium gleum by deoxyribonucleic acid-deoxyribonucleic acid homology data and phenotypic characteristics. Phenotypic characteristics useful to differentiate the two species are presented. PMID- 2325582 TI - The Mabel Liddiard memorial lecture 1989. Twins in the family. PMID- 2325583 TI - Agenda for action on the maternity services. PMID- 2325584 TI - Artificial milk advertising. PMID- 2325585 TI - The practical problems of neonatal ileostomy. PMID- 2325586 TI - The midwives' role in general practice maternity care. PMID- 2325587 TI - Left-right spatial agnosia and other mental defects that characterize clinical researchers. AB - There are mathematical rules for determining the logical significance of data, just as there are such rules for determining the statistical significance of data. Logical significance reflects the question a study is asking, whereas statistical significance reflects how well it has been answered. Clinical researchers routinely make an incorrect determination as to their study's logical significance because of a spatial (left-right) agnosia. More diffuse cognitive dysfunctions are encouraged by journals that expect clinicians to report on a study as a prerequisite for communicating their pre-existing opinions. The unwillingness or inability of the clinical community to acknowledge this problem reflects a related anosagnosia. PMID- 2325588 TI - Caution required in developing HIV vaccine. PMID- 2325590 TI - Differences between responsive and intractable chronic lymphocytic leukemia. AB - About 19-26% of patients with chronic lymphocytic leukemia (CLL) have intractable disease resistant to chemotherapy, have a relatively short median survival time and are responsive to splenectomy. Lymphocytes from patients with intractable CLL are resistant in vitro to X-irradiation and to colchicine. Responsive CLL is an accumulative disease while intractable CLL is a proliferative disease. PMID- 2325589 TI - The pathogenesis of vitreoretinal proliferation and traction: a working hypothesis. AB - Traction retinal detachment due to proliferative vitreoretinopathy (PVR) is a serious complication of ocular trauma, retinal detachment, and previous vitreoretinal surgery. The cause is the active proliferation of fibroblasts, glial cells, and retinal pigment epithelial cells in the periretinal spaces, leading to the formation of contractile cellular membranes. The generation of growth and mitosis stimulation for these cells has remained obscure. We postulate that invading macrophages and local microglia secrete growth factors, notably PDGF (platelet-derived growth factor), which in turn mediates the mitogenic effects of transferrin (TF), a protein present in huge amounts in native vitreous, in plasma and in intraocular proliferative tissue. PMID- 2325591 TI - Drug-positive homicides in Virginia 1987 through 1989. PMID- 2325592 TI - Blood pressure changes induced by ciclosporin A in type I diabetes. AB - The determinants of ciclosporin A-induced blood pressure changes were analyzed initially and after 3 months in 30 recent type I diabetics submitted to chronic treatment with ciclosporin as single immunosuppressive drug. Prevalence of hypertension was 17% and relatively low as compared to those reported in organ transplantation. Ciclosporin induced a slight decrease in glomerular filtration rate and renal plasma flow, with unchanged filtration fraction, a mild average increase in blood pressure and a more pronounced increase in renal vascular resistance. There was a trend toward decrease in absolute urinary sodium excretion whereas fractional excretion of sodium was unchanged. Presence of familial history of essential hypertension was characterized by a slightly insignificantly lower renal plasma flow and did not affect the renal effect of ciclosporin except that the renal plasma flow was significantly lower in the groups of patients genetically predisposed. PMID- 2325593 TI - IgA nephropathy: a long-term progressive study. AB - Thirty-three cases of idiopathic IgA nephropathy were followed up for an average of 90.8 +/- 8.4 months. Four therapeutic regimens were applied: symptomatic therapy, immunosuppressive drugs, dipyridamole with acetylsalicylic acid and immunomodulating treatment with thymosin. Parameters of kidney function obtained during control and treatment periods were compared in each patient separately. In all cases but one, frequent fluctuations of serum creatinine levels were observed. Cumulative kidney survival ratio for 5, 10 and 15 years amounted to 1.00, 0.90 and 0.82, respectively. There was no apparent response to thymosin, aspirin and dipyridamole therapy. Immunosuppressive drugs are recommended in cases with steadily progressive disease, when serum creatinine concentration surpasses 2.5 mg/dl. PMID- 2325594 TI - Failure to detect remarkable hypomagnesemia in renal transplant recipients receiving ciclosporin. AB - Serum magnesium as well as total and fractional urinary magnesium excretion were investigated in 87 renal transplant recipients under immunosuppression with azathioprine/prednisone (n = 18), ciclosporin/prednisone (n = 33) or ciclosporin/azathioprine/prednisone (n = 36). Only patients treated with ciclosporin and prednisone displayed significantly lower serum magnesium (1.8 +/- 0.03 mg/dl), compared to azathioprine-treated ones (2.0 +/- 0.07 mg/dl; p less than 0.05). Mean serum magnesium values of all three groups remained in the lower normal range (1.7-2.7 mg/dl). Fractional but not total magnesium excretion was significantly (p less than 0.05) higher in both ciclosporin-treated groups (5.8 +/- 0.38 and 5.6 +/- 0.40%) compared to patients on azathioprine (4.5 +/- 0.48%). None of the patients developed clinical signs of hypomagnesemia and only 7 patients were on oral supplementation with magnesium containing antacida. Our study did not confirm earlier observations of severe magnesium wasting and hypomagnesemia in renal transplant recipients under immunosuppression with ciclosporin. PMID- 2325595 TI - Assembly of terminal SC5b-9 complement complexes: a new index of blood-membrane interaction. AB - Activation of the complement system during the course of hemodialysis was recognized more than 20 years ago and since then the generation of C3a and C5a desarg has been used as parameters of blood-membrane interaction. More recently, determination of terminal C5b-9 complement complexes has become feasible. In the present study we determined plasma concentrations of C5b-9 complexes during hemodialysis using Cuprophan or Hemophan membranes. As early as 10 min into dialysis, Cuprophan membranes led to higher arterial plasma concentrations of C5b 9 complexes in comparison to Hemophan-containing devices. With Cuprophan, systemic arterial peak values of 237 +/- 27 U/ml were reached 45 min after the onset of dialysis, while corresponding peak values using Hemophan were only 58 +/ 16 U/ml. Venous concentrations of C5b-9 complexes, measured at the outlet of the dialyzer, were 489 +/- 102 U/ml with Cuprophan and 77 +/- 19 U/ml with Hemophan dialyzers. As an index of red cell lysis, plasma levels of free hemoglobin were evaluated. There was hemolysis with both membranes. Free hemoglobin levels increased threefold with Cuprophan and only twofold with Hemophan membranes. Taken together, plasma concentrations of C5b-9 complexes clearly discern between dialysis membranes of high or low compatibility. The fact that there is simultaneous lysis of red cells might indicate that deposition of C5b-9 complexes on innocent cells occurs which would lead subsequently to an array of diverse pathophysiological reactions. PMID- 2325596 TI - Indoor air quality and environmental tobacco smoke. PMID- 2325598 TI - Computed tomography demonstration of acute thrombosis of a portal vein aneurysm. AB - The author presents a case of surgically proven acute thrombosis of a portal vein aneurysm, a rare occurrence, demonstrated by computed tomography. PMID- 2325597 TI - Cardiovascular disease in Missouri: mortality, hospital discharges and risk factors. AB - The authors discuss the magnitude of cardiovascular disease in terms of mortality and medical care, while showing that significant proportions of Missourians are at risk of developing cardiovascular disease. PMID- 2325599 TI - Severe bradycardia and hypotension following intraocular acetylcholine in a patient who previously tolerated the medication. AB - Clinical problems with acetylcholine are unusual. The author's experience in the following case suggests that the mechanism of the observed side effects may be something other than drug idiosyncrasy, and stresses the importance of reporting side effects of medications. PMID- 2325600 TI - Update: influenza activity--worldwide and recommendations for influenza vaccine composition for the 1990-91 influenza season. PMID- 2325601 TI - [Effects of the administration of urinary trypsin inhibitor on the morphology and function of platelets in the rat septic models]. AB - Effects of urinary trypsin inhibitor (UTI) on the number, morphology and function of platelets under septic state were studied in rat models of cecal ligation and puncture (CLP). At formation of CLP, 5,000 U/kg/h of UTI was serially administered intraperitoneally and blood was sampled after 16 hours. Comparative study among sham-operation group, CLP group, and CLP + UTI group revealed: 1) inhibition of the platelets of platelet counts and appearance of large-sized, active platelets by UTI in the CLP + UTI group, 2) increase of platelet maximum aggregation rate (MAR) by ADP and increase of collagen in the CLP group, while inhibition in the CLP + UTI group and 3) by HPLC evaluation of adenine nucleotide in the platelet, increased levels of total ATP and ADP in the CLP group, particularly, increases of ATP in the metabolic pool and ADP in the granular pool. CLP + UTI group did not show these changes in the adenylate pool. UTI was thus considered to stabilize the platelet cycle in sepsis. Platelets under septic state might be hyperactive, and thrombosis is easy to occur. UTI administration might work for maintaining constancy of the platelet internal environment and improve septic state because adenine nucleotide level in the platelet did not change in the CLP + UTI group through changed in the CLP group. PMID- 2325602 TI - [A research on the cholestasis caused by continuous endotoxemia]. AB - Intrahepatic cholestasis is often observed in patients without obstruction of the bile duct, who are suffering from severe prolonged infection in the field of peptic surgery. Clinical data were analyzed in recently experienced 18 cases which showed this kind of jaundice. In those case, high rates of endotoxemia and high rates of gram negative bacilli were seen. This fact made us infer that endotoxins might cause jaundice. In order to clarify the mechanism of the jaundice, we made an experimental model of persistent endotoxemia in rats. Low dose endotoxin was infused continuously to Donryu-rats and bile-output was observed with external bile-guiding tube for 24 hours. In the endotoxin group, bile-output was significantly decreased whereas it was not changed in the control group. In addition, serum bilirubin was elevated in the endotoxin group, whereas it did not change in the control group. Blood-flow of liver tissue and systemic arterial blood pressure did not show any severe decrease under the continuous endotoxemia. Data of bile-output and bile acid showed bile acid independent flow might be depressed by endotoxin infusion. This model was thought to be under non shock condition and useful to investigate jaundice seen in patients under continuous endotoxemia. PMID- 2325603 TI - [Cytodynamic evaluation on the relationship between the mode of intracellular DNA content and the prognosis of esophageal cancer patients]. AB - In order to elucidate biological features of esophageal carcinoma influencing the prognosis of patients, intracellular DNA content was determined using a flow cytometry (FCM) apparatus. DNA ploidy patterns in 112 paraffin-embedded specimens removed at surgery were classified into 4 categories according to the shape of the first peak curve and the presence of the second peak curve. Type A: with symmetric single peak curve. (euploidy type) Type B: with asymmetric single peak curve. Type C: with the second small peak curve appearing on the right side of the first peak curve. Type D: with two obvious peak curves. Type B, C and D were grossly included in aneuploidy type, because of the presence of abnormal stem line. These DNA ploidy patterns were well correlated with histologic types. There were, however no significant differences in the relationship of DNA ploidy patterns and clinical stages. Four-year survival rate of the patients with euploidy pattern was 65.5%, and that with aneuploidy pattern was 15.7%, indicating a significant difference in survival between patients with the former pattern and those with the latter. The type of DNA ploidy was considered as one of the important prognostic indicators in patients with esophageal carcinoma independent of any other pathologic factors. PMID- 2325604 TI - [A study of bleeding peptic ulcer in the elderly in the view of risk factors]. AB - We treated 448 patients for peptic ulcer from 1970 to 1988. Among them, 52 cases were bleeding peptic ulcer in the elderly. 32 cases (61.6%) had a duration of illness of less than 3 months, and the most common symptom was abdominal pain (51.9%). 22 cases (44.0%) were in shock and 32 cases (62.7%) had accessory diseases. Twelve cases were treated medically, while 40 cases were treated surgically. Elective operations were performed in 15 cases, and their mortality was 6.7%. Emergent operations were performed in 25 cases, and their mortality was 28.0%. The mortality of of cases involving both shock and accessory diseases was 57.1%, and of this group, all 3 cases treated medically died. When bleeding exceeded 2000cc was the mortality 46.7%. Regarding cases of emergent operation involving shock or accessory diseases, the mortality was 18.2% in the cases treated medically for less than 4 days and had the episodes of massive bleeding less than 3 times, but 62.5% in other cases. The results of this study suggest that aggressive surgical treatment in an early stage may reduce the mortality in elderly patients with peptic ulcer. PMID- 2325605 TI - [A hybrid artificial liver system composed of primary cultured canine hepatocytes]. AB - The usefulness of newly device hybrid artificial liver system was evaluated in anhepatic dogs. The artificial liver module was composed of 60 to 80gm. primary cultured canine (Beagle) hepatocytes which were attached to 200 borocillicate glass plates. Total hepatectomy were done through cavo-caval and porto-caval shunt method using Anthron catheter to 14 dogs. Dogs were divided into following three groups. Group I; no treatment (n = 6) Group II; plasma perfusion (n = 4) Group III; treated with the artificial liver systems (n = 4) The survival times were 21.3 +/- 5.6, 27.8 +/- 4.0, and 55.0 +/- 11.3 hours in group I, II, and III, respectively. The longest survival time was 65 hours in one of group III dogs. APTT levels in group I and II increased more than 100 sec. within 24 hours. On the other hand it was maintained within 50 sec. during 54 hours treatment in group III. Ammonia levels in group I and II extremely increased over 2000ng/dl. In group III, it was less than 400ng/dl for 54 hours. Plasma amino acid levels in group I and II (Glutamine, Arginine, AAA) revealed significantly higher than in group III at 18 hours after operation. It is concluded that the newly device hybrid artificial liver system was useful for in vivo liver support. PMID- 2325606 TI - [Rationale of paraaortic lymph nodes dissection for advanced gallbladder cancer]. AB - Paraaortic lymph nodes dissection was performed routinely in 28 patients with advanced gallbladder cancer who underwent curative or relative non-curative resection. In 10 patients out of 28 (36%), metastasis was found in the dissected paraaortic nodes. The incidence of paraaortic lymph nodes metastasis was 50% when the gallbladder serosa or adjacent organs were involved by cancer. If routine paraaortic lymph nodes dissection had not been carried out, the operation would be regarded as curative in 4 patients out of 10 with paraaortic lymph nodes metastasis. The incidence of paraaortic lymph nodes metastasis was twice higher than that of the mesenteric root and the metastatic route was possibly derived directly from the retroportal and/or retropancreactic nodes. Therefore, we emphasize that the paraaortic nodes should be regarded as the nodes between the 2nd group such as the retroportal or retropancreatic nodes and the 3rd group including the nodes of mesenteric root. In spite of positive paraaortic nodes, mean survival time of the patients without other non-curative factors was 26 months and the longest survival was 42 months. It seems that paraaortic nodes dissection has palliative effects to prolong the survival period of those patients. Paraaortic lymph nodes dissection should be employed in radical operative procedures for advanced gallbladder cancer. PMID- 2325607 TI - [Basic and clinical evaluation of measurement of pancreatic cancer associated antigen, SPan-1]. AB - Basic evaluation of SPan-1 assay (SPan-1 RIA. BEAD) and clinical significance of serum SPan-1 levels for the diagnosis of pancreatic cancer were studied. This assay was reproducible, reliable and simple to perform. It required minimal samples (duplicate 50 microliters) and may be done within 4 hrs. Normal subjects (N = 1182) had serum SPan-1 antigen levels which ranged 0 to 42.8 units/ml with a mean of 7.5 units/ml and above 40 units/ml was considered to be positive. SPan-1 antigen levels in cultured medium of four out of five pancreatic cancer cell lines showed more than 1000 units/ml by this assay. While over 90% of pancreatic cancer patients had elevated levels of serum SPan-1 antigen, only 0-17% of patients with other malignant and non malignant gastrointestinal diseases such as pancreatitis (chronic or acute), gastric cancer or colon cancer had above normal levels. Furthermore, levels of serum SPan-1 antigen correlated well with treatment and recurrence of disease in patients with pancreatic and gastric cancer. These results suggest that determination of serum SPan-1 antigen levels by this assay kit is useful for the diagnosis and monitoring of pancreatic cancer. PMID- 2325608 TI - [Clinical study of radioisotopic splenoportography in portal hypertension]. AB - Radioisotopic splenoportography was performed in 55 patients with portal hypertension, in whom 52 had various degrees of esophagogastric varices, and in 20 patients without portal hypertension. In the patients with varices, collateral images were obtained in 50 patients (96%) by this method and no image was obtained in the patients without varices. The rate of positively imaged collaterals was as follows: Esophageal varices 69%, the left gastric vein 85%, the short gastric veins 48%, RI stasis in esophagogastric region 65%, the azygos vein 46%, the subclavian vein 25%, the para-umbilical veins 46%, splenorenal /gastrorenal shunts 19%, the inferior mesenteric vein 17%, the left intercostal veins 6%, and Arantius's duct 4%. These rates were superior to that obtained from the conventional transarterial portography. There were some correlations between RI-images by this method and clinical and laboratory findings; patients with ascending collaterals alone tended to have extensive and severe varices and higher rate of bleeding, on the other hand, variceal bleeding was not found and episodes of portosystemic encephalopathy frequently occurred in patients with descending collaterals alone. After successful sclerotherapy, RI-images of esophageal varices disappeared in 92% of the patients. Radioisotopic splenoportography appears to be a useful diagnostic and follow-up modality for patients with portal hypertension and esophagogastric varices. PMID- 2325609 TI - [Clinical evaluation of extended neck differentiated thyroid carcinoma]. AB - In some patients with advanced differentiated thyroid carcinoma, an upper mediastinal dissection is recommended. Both 17 primary and 6 non-primary patients who had undergone an upper mediastinal dissection in Shinshu University Hospital, from 1984 to 1987, were surveyed. We also studied 198 patients who had been performed a modified radical neck dissection from 1984 to 1986. In the 17 primary cases, 6 (35%) had positive nodes in the upper mediastinum (M group), and 11 (65%) negative (NM group). And we analysed these two groups. In addition, 5 non primary cases and 198 patients were analyzed in terms of the nodal metastatic status of the tumor-free side. From these results, we conclude the indication of mediastinal dissection for thyroid carcinoma as follows: (1) positive lymph node is suspected in the upper mediastinum by the study of CT or 201thallium scintigram. (2) nodal metastases are suspected in the deep cervical location of the tumor-free side. (3) a male patient whose age is younger than 50, and tumor is located in the left lobe and its size is larger than 3.0 cm. PMID- 2325610 TI - [Plasma and tumor gastrin in patients with primary hyperparathyroidism]. AB - It is well known that primary hyperparathyroidism is often associated with peptic ulcer. The purpose of this study is to confirm the relationship between the gastrin-levels before and after parathyroidectomy in fourteen patients with primary hyperparathyroidism, and to determine the localization of gastrin in the surgically resected parathyroid tumor. The results obtained were as follows: 1) Three patients had peptic ulcer (gastric ulcer and duodenal ulcer), the incidence being 21%. 2) The basal serum gastrin levels were 123.0% +/- 68.1 pg/ml before operation and decreased to 90.2 +/- 44.5 pg/ml after operation. In the 3 patients with slightly elevated gastrin levels, the mean level before operation was 209.1 +/- 61.2 pg/ml. The gastrin level decreased to 116.4 +/- 62.0 pg/ml after operation. 3) Gastrin immunoreactivity was detected in 10 out of 14 tumors and its localization was at the periphery of tumor cells. From these results, we conclude that extragastric gastrin secretion from parathyroid tumors may be one of the cause of peptic ulcer in patients with primary hyperparathyroidism. PMID- 2325611 TI - [Clinical analysis of the patients with delayed sternal closure following open heart surgery]. AB - Thirteen patients with successful or unsuccessful delayed sternal closure (DSC) after open heart surgery were reviewed. The indications of DSC were cardiac dilatation in 12 patients and intractable bleeding in one. Patients were divided into two groups as follows: Group A of 7 patients with mediastinum being sealed by prosthetic material, and Group B of 6 patients with primary skin closure by mobilized skin-flap. Postoperative complications and prognosis were compared between these two groups. There were 6 long term survivors. In group A, there were 4 deaths, 2 from low output syndrome (LOS) and 2 from sepsis due to mediastinitis. In group B, 2 died of LOS and 1 died of multiple organ failure, while no patients developed mediastinitis. In patients with unsuccessful DSC, mainly due to poor hemodynamics, there found no tendencies of decrease in CVP and LAP levels and no reduction in the amount of catecholamine dosage prior to attempted DSC. In conclusion, 1) mediastinal isolation with primary skin closure seemed more effective for preventing mediastinitis than coverage with prosthetic materials, 2) DSC was possible when there were hemodynamic improvements with decrease in CVP and LAP levels, and reduction in catecholamine dosage, and 3) plastic surgical technique was useful for primary skin closure. PMID- 2325612 TI - [Experimental studies on extracorporeal membrane oxygenation (ECMO) perfusion for respiratory insufficiency associated with pulmonary hypertension]. AB - Some types of neonatal respiratory insufficiency may be associated with severe pulmonary hypertension. This paper evaluates two methodologies of ECMO perfusion in the treatment of such serious respiratory insufficiency. Pulmonary hypertension was prepared in dogs by administering small pieces of gelatin sponge into the main pulmonary artery. The two methodologies of perfusion were venoarterial bypass (VAB) and venovenous bypass (VVB). Prior to ECMO perfusion, oxygen supplementation during perfusion and hemodynamics were examined. Oxygen supplementation was satisfactory in both VAB and VVB. With VAB, the mean pulmonary artery pressure (mPAP) was significantly dropped from 33.8 +/- 3.1 mmHg to 28.4 +/- 6.2 mmHg, the pulmonary blood flow (PBF) being significantly declined from 1.39 +/- 0.21 L/min to 1.07 +/- 0.15 L/min. With VVB, mPAP was significantly dropped from 33.9 +/- 6.2 mmHg to 29.1 +/- 5.1 mmHg, the pulmonary vascular resistance (PVR) being significantly decreased from 1983.1 +/- 656.0 dynes.sec.cm 5 to 1740.4 +/- 635.9 dynes.sec.cm-5. It is considered that VAB renders PBF decline, which induces a drop in PAP, while VVB accelerates a flow of well oxygenated blood in the pulmonary artery, which results in a decline in PVR and then a drop in PAP. VVB as well as VAB is useful in the treatment of neonates with respiratory insufficiency who present with pulmonary hypertension. PMID- 2325613 TI - [A case report of five-year survival with repeated resection of metastases from jejunal leiomyosarcoma]. AB - A case of five-year survival of jejunal leiomyosarcoma with metastases to the liver and mesentery treated with four times surgery was reported here. Four metastatic lesions were detected in the sigmoid mesocolon once and in the liver three times and resected with hope of cure. The patient, a 37 years old male, tolerated surgical procedures including an extended right hepatic lobectomy and recovered each time. He is leading a satisfactory daily life 5 years and 3 months after the initial operation although multiple liver metastases were detected 10 months after the fourth operation. A positive surgical therapy is advocated in selected patients who have spreading leiomyosarcoma of the bowel. PMID- 2325614 TI - [Obstructive jaundice from benign hepatic cysts]. AB - Obstructive jaundice secondary to benign, non-parasitic hepatic cysts is rare, since there are only 19 previously reported cases. We reported a case of polycystic disease of the liver and kidneys in which relief of developing jaundice was obtained by hepatic lobectomy and fenestration procedure for the multiple cysts. Immense occupancy and porta hepatis proximity of the cysts were triggers for developing jaundice. Urgent resection of the major cysts is recommended for extremely progressing jaundice. PMID- 2325615 TI - [Membranous obliteration of the inferior vena cava in the hepatic portion- postmortem study of a rapidly deteriorated aged case]. AB - A 67-year-old female of Budd-Chiari syndrome was rapidly deteriorated and died. Autopsy revealed membranous obliteration of the inferior vena cava in the hepatic portion with a small hole. The inferior vena cava and right hepatic vein contained fresh and organized thrombi. The left hepatic vein was patent and opened above the membrane. The onset and the clinical course of this case seem to be atypical, probably because of the patent left hepatic vein and a small hole of the membrane. We call attention such a rare case in managing Budd-Chiari syndrome. PMID- 2325616 TI - [Inhibitory effect of fibronectin on metastasis of Lewis lung carcinoma in mice: preliminary report]. PMID- 2325617 TI - [A new reliable model for ischemic colitis: preliminary report]. PMID- 2325618 TI - [Abdominal multi-organ transplantation: an experimental study]. PMID- 2325619 TI - [Intraoperative assessment of the transmural myocardial blood flow distribution using myocardial contrast echocardiography: preliminary report]. PMID- 2325621 TI - Evidence for the expression of the rol genes of Nicotiana glauca in genetic tumors of N. glauca X N. langsdorffii. AB - Thus far, no evidence has been presented that the rol genes (Ng rol) of Nicotiana glauca (Furner et al. 1986) are expressed in this plant. However, we found that the Ng rol genes were transcribed in genetic tumors formed in hybrids of N. glauca X N. langsdorffii. During the culture of such genetic tumors, the level of transcription of Ng rol B increased while that of Ng rol C decreased in parallel with an increase in the endogenous auxin level in the tissues. Moreover, the transcription of these genes was completely suppressed by the application of exogenous auxin. Since the measured endogenous level of auxin was rather low, the formation of tumors in these hybrids can be tentatively explained as a consequence of the expression of rol genes that is responsible for the increased sensitivity to auxin of the hybrids. This novel finding is discussed in relation to the cause of genetic tumors in Nicotiana. PMID- 2325620 TI - Linear plasmid DNAs of the plant pathogenic fungus Rhizoctonia solani with unique terminal structures. AB - Three linear DNA plasmids were found in isolate RI-64 of anastomosis group 4 (AG 4) of Rhizoctonia solani. These plasmids, designated pRS64-1, -2, and -3, possessed the same size of 2.7 kb. Restriction mapping and Southern hybridization analysis of pRS64-1, -2, and -3 revealed the presence of homologous regions at both termini. The plasmid DNAs were resistant to both 3'-exonuclease and 5' exonuclease even after treatment with proteinase K or alkali. The length of both terminal fragments that were generated by restriction endonuclease digestion was doubled under the denaturation condition, indicating that the linear plasmid DNAs have hairpin loops at both termini. Southern blotting analysis of total DNA showed the presence of two types of dimeric forms of pRS64 DNA. One is a head-to head dimer and the other is a tail-to-tail dimer. The role of these unique DNA structures in replication of the plasmids is discussed. PMID- 2325622 TI - Novel replication mutant of microvirid phage alpha 3 deleted in the complementary strand origin. AB - The bacteriophage alpha 3 origin of complementary strand DNA synthesis (-ori) contains two potential secondary loop structures (I and II), which have been implicated as direct recognition sites for host Escherichia coli DnaG protein. To elucidate to what extent such structures are essential, we introduced a nucleotide deletion within the -ori region, by nuclease digestion of alpha 3 replicative form DNA. A mutant, delB, thus constructed had a 121 nucleotide deletion within the -ori region and was completely lacking in the two putative hairpin loops, I and II. The delB mutant formed smaller plaques on the host E. coli C and had a longer latent period, but the mean burst size at 37 degrees C was almost the same (400 phages) as that of the wild type. In contrast to the parental phage, growth of the mutant depends on host dnaB and dnaC functions. These results indicate that the prototype secondary structures in the alpha 3 origin of complementary strand synthesis are dispensable for delB and that the alpha 3 mutant has an additional replication origin whose function is dependent on DnaB and DnaC proteins, rather than on DnaG protein alone. PMID- 2325623 TI - Construction of an intron-containing marker gene: splicing of the intron in transgenic plants and its use in monitoring early events in Agrobacterium mediated plant transformation. AB - Agrobacterium tumefaciens is a commonly used tool for transforming dicotyledonous plants. The underlying mechanism of transformation however is not very well understood. One problem complicating the analysis of this mechanism is the fact that most indicator genes are already active in Agrobacterium, thereby preventing the precise determination of timing and localisation of T-DNA transfer to plant cells. In order to overcome this obstacle a modified prokaryotic indicator gene was constructed. The expression of this indicator gene and its use in analysing early events in Agrobacterium-mediated plant transformation are described. A portable intron, derived from a plant intron, was introduced into the beta glucuronidase (GUS) gene. In transgenic plants containing this chimaeric gene the intron is spliced efficiently, giving rise to GUS enzymatic activity. Mapping of the splice junction indicates the exact removal of the intron. No GUS activity is detected in agrobacteria containing this construct due to the lack of a eukaryotic splicing apparatus in prokaryotes. Early phases after transformation of Arabidopsis cotyledon explants were analysed using this GUS-intron chimaeric gene showing that as early as 36 h after Agrobacterium infection significant GUS activity is detected. In vivo GUS staining of transformed cells clearly shows that quickly proliferating calli expressing GUS activity are formed, mainly at the cut surface. Minor transformation events occur however throughout the whole cotyledon. These data indicate that Agrobacterium-mediated T-DNA transfer to plants is much more efficient than has been judged from experiments where selection is applied immediately. The intron-containing GUS gene can be used as an optimised marker gene in transient and stable transformation experiments. PMID- 2325625 TI - Expression of the beta-glucuronidase gene under the control of the CaMV 35s promoter in Schizosaccharomyces pombe. AB - We have transformed Schizosaccharomyces pombe with the beta-glucuronidase (GUS) gene from Escherichia coli under the control of the plant cauliflower mosaic virus (CaMV) 35S promoter element. Efficient expression of GUS enzyme was observed. Moreover, transcription initiated at a unique site identical to that used in plant cells. PMID- 2325624 TI - Location and organization of the dimethylphenol catabolic genes of Pseudomonas CF600. AB - The gene organization of the phenol catabolic pathway of Pseudomonas CF600 has been investigated. This strain can grow on phenol and some methylated phenols by virtue of an inducible phenol hydroxylase and metacleavage pathway enzymes. The genes coding for these enzymes are located on pVI150, an IncP-2 degradative mega plasmid of this strain. Twenty-three kilobases of contiguous DNA were isolated from lambda libraries constructed from strains harbouring wild type and Tn5 insertion mutants of pVI150. A 19.9 kb region of this DNA has been identified which encodes all the catabolic genes of the pathway. Using transposon mutagenesis, polypeptide analysis and expression of subfragments of DNA, the genes encoding the first four enzymatic steps of the pathway have been individually mapped and found to lie adjacent to each other. The order of these genes is the same as that for isofunctional genes of TOL plasmid pWWO and plasmid NAH7. PMID- 2325626 TI - Comparison of the CopB systems of plasmids R1 and ColV2-K94: a single base alteration in CopB gene is responsible for the increased copy number of the low copy number plasmid ColV2-K94. AB - We have isolated a deletion mutation and a point mutation in the copB gene of the replication region Repl of the IncFI plasmid ColV2-K94. Subsequently, this copB gene with and without point mutation was cloned and sequenced, and the point mutation was mapped in the coding region of copB with a change of one amino acid from arginine to serine. Furthermore, this copB mutant had an approximately 10 fold increase in copy number. The CopB-phenotype of ColV2-K94 could be complemented in trans by the copB gene of coresident IncFII plasmids such as R1 and R538, but not R100, suggesting that ColV2-K94 and R1 or R538 contain the same copB allele. PMID- 2325628 TI - Transcription of tomato ribosomal DNA and the organization of the intergenic spacer. AB - The organization of the intergenic spacer of a 9.04 kb tomato ribosomal RNA gene (rDNA) was determined. The 3258 bp spacer contains two major repeat elements enclosing a region which includes 351 bp of an 81.8% A --T rich sequence. A block of nine 53 bp repeats begins 388 bp downstream from the 3' end of the 25S rRNA. The A--T rich domain is followed by a block of six 141 bp repeats terminating 818 bp upstream from the 5' end of the 18S rRNA. Major pre-rRNAs of 7.6 and 6.5 kb were observed by Northern hybridization analysis. The 5' termini of these RNAs were identified through combined S1 nuclease and primer extension analyses. The 7.6 kb RNA is likely to be the primary transcript; its 5' terminus lies within a sequence motif. TATA(R)TA(N)GGG, conserved at the termini of transcripts mapped in three other plant species. The 6.5 kb RNA is interpreted as a 5' end processed transcript derived from the 7.6 kb RNA. Comparative analysis of transcribed sequences revealed a 25 bp domain of the intergenic spacer which is relatively conserved among five plant species. The conservation of spacer sequences in plants is in contrast to the extensive sequence divergence of the intergenic spacer in other non-plant systems and suggests a conserved function directed by these sequences. PMID- 2325627 TI - Nucleotide sequence of the staphylococcal enterotoxin C3 gene: sequence comparison of all three type C staphylococcal enterotoxins. AB - The structural gene entC3, which encodes staphylococcal enterotoxin C3 was cloned from the genome of Staphylococcus aureus FRI-913 and sequenced. The primary amino acid sequence of the toxin was deduced from the nucleotide sequence data. entC3 contains 801 bp and encodes a precursor protein of 266 amino acids. Glutamic acid was found to be the N-terminus of mature enterotoxin C3. Thus, the first 27 residues of the toxin precursor comprise the signal peptide, and the mature toxin contains 239 amino acids with a molecular weight of 27,563 daltons. Enterotoxin C3 differs from enterotoxin C2 by four amino acids and from enterotoxin C1 by nine residues. The 167 C-terminal residues of the three toxins are identical, except for one conservative amino acid substitution in enterotoxin C3. The degree of immunological relatedness among the three Type C enterotoxins is proportional to their molecular relatedness. This study also provides evidence that the N termini of Type C enterotoxins determine subtype-specific antigenic epitopes, while more conserved C-terminal regions determine biological properties and cross reactive antigenic epitopes shared with other pyrogenic toxins. PMID- 2325629 TI - Synthesis of saporin gene probes from partial protein sequence data: use of inosine-oligonucleotides, genomic DNA and the polymerase chain reaction. AB - A strategy employing the polymerase chain reaction to synthesize gene-specific probes suitable for genomic Southern analyses and for screening genomic libraries is described. The method utilizes partial amino acid sequence data from the protein of interest, genomic DNA and inosine-containing oligonucleotide primers. An example of its application for the isolation of plant gene sequences encoding saporin, a ribosome inactivating protein, is described. PMID- 2325630 TI - Coding sequence and flanking regions of the mouse vimentin gene. AB - Using a polyclonal antibody, a cDNA clone coding for part of mouse vimentin was identified in a lambda gt11 expression library. DNA from this clone was used to screen a genomic library from Ehrlich Ascites Tumor cells for the mouse vimentin gene. A clone was found which contained the whole coding sequence and a large part of the 5'- and 3'-untranslated sequences. It was used to prepare a construct equivalent to a full-length cDNA clone. Extensive homologies to the vimentin sequence from other species were found for the coding and 3'-untranslated sequences and the promoter region. PMID- 2325631 TI - Cloning and sequencing the genes encoding uptake-hydrogenase subunits of Rhodocyclus gelatinosus. AB - Rhodocyclus gelatinosus grew photosynthetically in the light and consumed H2 at a rate of about 665 nmol/min per mg protein. The uptake-hydrogenase (H2ase) was found to be membrane bound and insensitive to inhibition by CO. The structural genes of R. gelatinosus uptake-H2ase were isolated from a 40 kb cosmid gene library of R. gelatinosus DNA by hybridization with the structural genes of uptake-H2ase of Bradyrhizobium japonicum and Rhodobacter capsulatus. The R. gelatinosus genes were localized on two overlapping DNA restriction fragments subcloned into pUC18. Two open reading frames (ORF1 and ORF2) were observed. ORF1 contained 1080 nucleotides and encoded a 39.4 kDa protein. ORF2 had 1854 nucleotides and encoded a 68.5 kDa protein. Amino acid sequence analysis suggested that ORF1 and ORF2 corresponded to the small (HupS) and large (HupL) subunits, respectively, of R. gelatinosus uptake-H2ase. ORF1 was approximately 80% homologous with the small, and ORF2 was maximally 68% homologous with the large subunit of typical membrane-bound uptake-H2ases. PMID- 2325632 TI - Molecular analysis of zyg-11, a maternal-effect gene required for early embryogenesis of Caenorhabditis elegans. AB - The product of the maternally acting gene zyg-11 is required for early embryogenesis of Caenorhabditis elegans. One-cell embryos that lack a functional zyg-11 gene product exhibit an arrest of meiosis at metaphase II, a delay in the formation of pronuclei, unusually vigorous movements of cytoplasm, the formation of multiple pronuclei, incorrect segregation of P granules, and incorrect placement of the first cleavage furrow. We have isolated and sequenced a molecular clone of zyg-11, and shown that microinjection of the cloned DNA can rescue zyg-11 mutations. A transcriptional analysis shows that transcription of the gene is not limited to the female germ-line, despite the strict maternal effect phenotype of zyg-11 mutations. PMID- 2325633 TI - Cloning and sequence analysis of the arginine deiminase gene from Mycoplasma arginini. AB - Arginine deiminase from Mycoplasma arginini was purified. The purified enzyme has a molecular weight of 46,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Its specific activity (20 units/mg protein) and amino acid composition showed a strong similarity to that of the Mycoplasma arthritidis arginine deiminase. The amino acid sequences of the N-terminal region and three internal peptides generated by enzymatic cleavage of the purified protein were determined. Using a synthetic oligonucleotide mixture complementary to part of the determined N-terminal amino acid sequence, the gene coding for arginine deiminase was isolated from a phage library. A nucleotide sequence of 2189 bp encoding the gene was determined. An open reading frame (ORF) contained the amino acid sequences corresponding to the determined N-terminal region and the three internal peptides of arginine deiminase. Thus it was concluded that this ORF encoded the arginine deiminase, a 385 amino acid polypeptide (mol.wt. 43,900 daltons). The three tryptophan residues in the sequenced peptides align with UGA codons in the nucleotide sequence, indicating that the nonsense codon UGA is used as a tryptophan codon in M. arginini. PMID- 2325634 TI - Formation of composite nucleoprotein complexes near the transcription start of the Shrunken gene from maize. AB - We describe an analysis of protein-DNA interactions detectable with nuclear extracts prepared from maize kernels and DNA fragments from the immediate upstream region of the Shrunken gene from maize. The data demonstrate that sequences from position -235 to the transcription start are recognized by sequence specific nuclear proteins. In footprinting and competition experiments at least six different protein-DNA interactions can be distinguished within this upstream region. Two sequence related inverted repeat structures, 67 and 64 bp in length, cross compete for protein recognition. PMID- 2325635 TI - KT5926, a potent and selective inhibitor of myosin light chain kinase. AB - KT5926, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3 ,9, 10-tetrahydro-8,11-epoxy, 1H,8H, 11H-2,7b,11a triazadibenzo[a,g]cycloocta[cde] trinden-1-one, was found to be a potent and selective inhibitor of myosin light chain kinase. The compound inhibited both Ca2+/calmodulin-dependent and -independent smooth muscle myosin light chain kinases to a similar extent. The inhibition was not affected by the concentration of calmodulin. Kinetic analyses showed that the mode of inhibition was of the competitive type with respect to ATP (Ki, 18 nM) and of the noncompetitive type with respect to myosin light chain (Ki, 12 nM). These results indicated that KT5926 directly interacted with the enzyme at the catalytic site. KT5926 also inhibited other protein kinases, but with relatively high Ki values; the values for protein kinase C, cAMP-dependent protein kinase, and cGMP-dependent protein kinase were 723, 1200, and 158 nM, respectively. Ca2(+)-ATPase, Na+/K(+)-ATPase, hexokinase, and 5'-nucleotidase were not inhibited by KT5926 at less than 10 microM. The effect of KT5926 on serotonin secretion and protein phosphorylation induced by platelet-activating factor or phorbol ester was examined in rabbit platelets. KT5926 inhibited the phosphorylation of a 20-kDa protein but had no effect on the phosphorylation of a 40-kDa protein, thereby indicating that the compound exerts its selective inhibition of myosin light chain kinase in intact cells. The compound inhibited serotonin secretion induced by platelet-activating factor, but its potency was significantly less than that of K-252a, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9, 10-tetrahydro-8,11 epoxy-1H,8H,11H-2,7b, 11a-triazadibenzo[a,g]cycloocta [cde]trinden-1-one, which inhibited the phosphorylation of both the 20-kDa protein and the 40-kDa protein. Phorbol ester-induced secretion was not suppressed by KT5926. These results provide the evidence that both the 20-kDa protein phosphorylation by myosin light chain kinase and the 40-kDa protein phosphorylation by protein kinase C substantially contribute to the secretion response in platelets. PMID- 2325636 TI - Single amino acid substitution defines a naturally occurring genetic variant of human thymidylate synthase. AB - Previously, we identified an altered structural form of thymidylate synthase (TS) in a human colonic tumor cell line. This form, which is encoded by a variant structural gene, renders cells relatively resistant to 5-fluoro-2'-deoxyuridine as a result of the reduced affinity of the enzyme for the active metabolite 5 fluoro-2'-deoxyuridylic acid. We have isolated a cDNA clone specific to the altered TS and have determined its sequence. Two point mutations distinguish the normal from the altered TS mRNAs. One, a (A----G) change, is located within the 3'-untranslated region; the other, a T----C change within the amino acid-coding region, predicts replacement of tyrosine by histidine at residue 33 of the polypeptide. This sequence change was confirmed by direct analysis of cDNA amplified by the polymerase chain reaction and was further verified using allele specific oligonucleotides as probes in Northern blots. These results, along with studies by other laboratories showing Tyr33 to be evolutionarily conserved, suggest that this residue plays an important role in TS function. PMID- 2325637 TI - Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein. AB - The ubiquitous adenosine A2-like binding protein obscures the binding properties of adenosine receptors assayed with 5'-N-[3H]ethylcarboxamidoadenosine [( 3H]NECA). To solve this problem, we developed a rapid and simple method to separate adenosine receptors from the adenosine A2-like binding protein. Human platelet and placental membranes were solubilized with 1% 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate. The soluble platelet extract was precipitated with polyethylene glycol and the fraction enriched in adenosine receptors was isolated from the precipitate by differential centrifugation. The adenosine A2-like binding protein was removed from the soluble placental extract with hydroxylapatite and adenosine receptors were precipitated with polyethylene glycol. The specificity of the [3H]NECA binding is typical of an adenosine A2 receptor for platelets and an adenosine A1 receptor for placenta. This method leads to enrichment of adenosine A2 receptors for platelets and adenosine A1 receptors for placenta. This provides a useful preparation technique for pharmacologic studies of adenosine receptors. PMID- 2325638 TI - Analysis of the upstream elements of the xenobiotic compound-inducible and positionally regulated glutathione S-transferase Ya gene. AB - In situ hybridization and other data showed that all hepatocytes express glutathione-S-transferase (GST) Ya mRNA but that specifically pericentral cells can be induced 15- to 20-fold with 3-methylcholanthrene (3-MC). In order to identify DNA sequences involved in inducible expression (pericentral hepatocytes) and constitutive expression (all hepatocytes), the upstream regions of the GST Ya gene were further analyzed by transient transfection and DNA-binding studies to identify the nature of proteins involved in regulating this gene. The sequences from -980 to -650 were necessary and sufficient for cell-specific and inducible expression. Within this enhancer region, four nuclear protein-binding sites were identified. One site required for inducible expression was bound by a protein(s) induced by 3-MC. Two other sites were bound by proteins similar or identical to the constitutive hepatocyte nuclear factors HNF1 and HNF4. The fourth site was shown to be bound by a non-liver-specific nuclear protein that is also important in the function of the albumin gene enhancer. PMID- 2325639 TI - Functional analysis of a centromere from fission yeast: a role for centromere specific repeated DNA sequences. AB - A circular minichromosome carrying functional centromere sequences (cen2) from Schizosaccharomyces pombe chromosome II behaves as a stable, independent genetic linkage group in S. pombe. The cen2 region was found to be organized into four large tandemly repeated sequence units which span over 80 kilobase pairs (kb) of untranscribed DNA. Two of these units occurred in a 31-kb inverted repeat that flanked a 7-kb central core of nonhomology. The inverted repeat region had centromere function, but neither the central core alone nor one arm of the inverted repeat was functional. Deletion of a portion of the repeated sequences that flank the central core had no effect on mitotic segregation functions or on meiotic segregation of a minichromosome to two of the four haploid progeny, but drastically impaired centromere-mediated maintenance of sister chromatid attachment in meiosis I. This requirement for centromere-specific repeated sequences could not be satisfied by introduction of random DNA sequences. These observations suggest a function for the heterochromatic repeated DNA sequences found in the centromere regions of higher eucaryotes. PMID- 2325640 TI - Cleavage of a hydrophilic C-terminal domain increases growth-inhibitory activity of oncostatin M. AB - Oncostatin M is a polypeptide cytokine, produced by normal and malignant hematopoietic cells, that has several in vitro activities, including the ability to inhibit growth of cultured carcinoma cells. Here we present a structural and functional comparison of two oncostatin M-related proteins (Mr 36,000 and 32,000) secreted by COS cells transfected with oncostatin M cDNA. The smaller of these forms lacked a hydrophilic C-terminal domain comprising predominantly basic amino acids. This domain was also absent from native oncostatin M produced by U937 cells. The 32,000-Mr form of oncostatin M was not produced by cells transfected with plasmids (G195 and G196) in which a potential trypsinlike cleavage site within the hydrophilic C-terminal domain was altered by site-directed mutagenesis. A 32,000-Mr fragment was produced by trypsin treatment of the 36,000 Mr form of oncostatin M. These observations suggest that the 32,000-Mr form of oncostatin M was derived from the 227-amino-acid propeptide by proteolytic cleavage at or near the paired basic residues at positions 195 and 196. Pro oncostatin M was equally active in radioreceptor assays as the processed form but was 5- to 60-fold less active in growth inhibition assays. Likewise, nonprocessed mutant protein encoded by plasmid G196 was equally active in the radioreceptor assays as the processed form but was five- to ninefold less active in growth inhibition assays. Thus, the highly charged C-terminal domain of pro-oncostatin M is not required for receptor binding or growth-inhibitory activity but may alter the functional properties of the molecule. Propeptide processing of oncostatin M may be important for regulating in vivo activities of this cytokine. PMID- 2325641 TI - Unusual features of integrated cDNAs generated by infection with genome-free retroviruses. AB - We previously demonstrated that when nonretroviral RNAs are encapsidated in retroviral particles they can be reverse transcribed into cDNAs, which are then integrated into the cellular genome. This transfer of genetic information via retroviral infection has been designated retrofection. Further analyses of three genes transferred in this manner (retrogenes) revealed that each was present in a single copy at a different site in the recipient quail cell genome and included a transcriptional promoter encoded by the encapsidated neo RNA. A unique feature of the retrogenes was a common 16-nucleotide sequence at or near a recombination border, which was not present in either recombination partner. The existence of this sequence suggests a common mechanism of retrogene formation and/or integration mediated by retrofection. PMID- 2325642 TI - Identification of positive and negative regulatory elements governing cell-type specific expression of the neural cell adhesion molecule gene. AB - The neural cell adhesion molecule (NCAM) is one of the most prevalent cell adhesion molecules in vertebrates. Its expression is subject to complex cell-type and developmental-stage-dependent regulation. To study this regulation at the level of transcription, we analyzed the promoter region of the mouse NCAM gene. The NCAM promoter did not contain a typical TATA box. Transcription started at several sites that were used indiscriminately by different cell types, implying that the different NCAM isoforms are expressed from a single promoter. Sequences responsible for both promotion and inhibition of transcription resided within 840 base pairs upstream of the main transcriptional start site. The sequence from positions -645 to -37 relative to the translation initiation site directed high levels of expression in NCAM-expressing N2A cells. The same fragment was six times less active but still significantly active in L cells, but this activity was repressed by inclusion of an additional upstream segment. We mapped eight domains of interactions with nuclear proteins within the 840-base-pair region. The segment with maximum promoter activity contained two adjacent footprints, the occupation of which appeared to be mutually exclusive. One of them corresponded to an Sp1-factor-binding consensus site, the other one bound a factor with nuclear factor I activity. The single protected domain in the fragment harboring a repressor activity consisted of a GGA repeat resembling negative regulatory elements in other promoters. Three adjacent binding sites occupied an A + T-rich segment and contained ATTA motifs also found in the recognition elements of homeodomain proteins. These results show that negative and positive elements interact to regulate the tissue-specific patterns of expression of the NCAM gene and indicate that a factor related to nuclear factor I is involved in its transcriptional control. PMID- 2325644 TI - A constitutive damage-specific DNA-binding protein is synthesized at higher levels in UV-irradiated primate cells. AB - Using a DNA band shift assay, we have identified a DNA-binding protein complex in primate cells which is present constitutively and has a high affinity for UV irradiated, double-stranded DNA. Cells pretreated with UV light, mitomycin C, or aphidicolin have higher levels of this damage-specific DNA-binding protein complex, suggesting that the signal for induction can either be damage to the DNA or interference with cellular DNA replication. Physiochemical modifications of the DNA and competition analysis with defined substrates suggest that the most probable target site for the damage-specific DNA-binding protein complex is a 6 4'-(pyrimidine-2'-one)-pyrimidine dimer: specific binding could not be detected with probes which contain -TT- cyclobutane dimers, and damage-specific DNA binding did not decrease after photoreactivation of UV-irradiated DNA. This damage-specific DNA-binding protein complex is the first such inducible protein complex identified in primate cells. Cells from patients with the sun-sensitive cancer-prone disease, xeroderma pigmentosum (group E), are lacking both the constitutive and the induced damage-specific DNA-binding activities. These findings suggest a possible role for this DNA-binding protein complex in lesion recognition and DNA repair of UV-light-induced photoproducts. PMID- 2325643 TI - The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity. AB - We have isolated the gene for a novel growth regulator, amphiregulin (AR), that is evolutionarily related to epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). AR is a bifunctional growth modulator: it interacts with the EGF/TGF-alpha receptor to promote the growth of normal epithelial cells and inhibits the growth of certain aggressive carcinoma cell lines. The 84-amino-acid mature protein is embedded within a 252-amino-acid transmembrane precursor, an organization similar to that of the TGF-alpha precursor. Human placenta and ovaries were found to express significant amounts of the 1.4-kilobase AR transcript, implicating AR in the regulation of normal cell growth. In addition, the AR gene was localized to chromosomal region 4q13 4q21, a common breakpoint for acute lymphoblastic leukemia. PMID- 2325645 TI - Nuclease activity associated with mammalian mRNA in its native state: possible basis for selectivity in mRNA decay. AB - Polysome and messenger ribonucleoprotein (mRNP) preparations from various mammalian cells contain tightly bound nuclease activity that causes degradation of the mRNA in the preparations. This activity was found to cosediment with all polysome size classes as well as with free mRNPs and to remain associated with the mRNPs released from polysomes by treatment with EDTA. No association with ribosomal subunits was evident. The rates of mRNA degradation were not affected by serial dilution, an indication that enzyme and substrate are tightly associated. beta-Globin mRNA in purified reticulocyte polysomes was cleaved at AU sequences in the 3'-terminal region. Cleavages at the same sites occurred when deproteinized reticulocyte RNA was incubated with mouse sarcoma 180 (S-180) polysomes. The S-180 preparations caused additional cleavages, primarily at UG sequences. A P40 mRNA in S-180 polysomes was cleaved primarily in the 3' noncoding region, but the cleavages in a P21 mRNA were seen in the 5' noncoding region only. Actin mRNA was cleaved in an internal region, yielding large relatively stable 3'- and 5'-terminal fragments. These data suggest the occurrence of highly specific interactions between one or more mRNA-bound nucleases and individual mRNA species. PMID- 2325646 TI - Amplification of tandemly repeated origin control sequences confers a replication advantage on rDNA replicons in Tetrahymena thermophila. AB - The macronuclear rRNA genes (rDNA) in the ciliate Tetrahymena thermophila are normally palindromic linear replicons, containing two copies of the replication origin region in inverted orientation. A circular plasmid containing a single Tetrahymena rRNA gene (one half palindrome) joined to a tandem repeat of a 1.9 kilobase (kb) rDNA segment encompassing the rDNA replication origin and known replication control elements was used to transform Tetrahymena macronuclei by microinjection. This plasmid was shown previously to have a replication advantage over the rDNA allele of the recipient cell strain (G.-L. Yu and E. H. Blackburn, Proc. Natl. Acad. Sci. USA 86:8487-8491, 1990). During vegetative cell divisions, the circular and palindromic rDNAs were rapidly replaced by novel, successively longer linear rDNAs that eventually contained up to 30 tandem 1.9-kb repeats, resulting from homologous but unequal crossovers between the 1.9-kb repeats. We present evidence to show that increasing the number of copies of the replication control regions increases the replicative advantage of the rDNA, the first such situation for a cellular nuclear replicon in a eucaryote. PMID- 2325647 TI - Characterization of the rat transforming growth factor alpha gene and identification of promoter sequences. AB - We have determined the complete nucleotide sequence of rat transforming growth factor alpha (TGF alpha) mRNA and characterized the six exons that encode this transcript. These six exons span approximately 85 kilobases of genomic DNA, with exons 1 to 3 separated by particularly large introns. What had previously been thought to represent a species-specific difference in the size of the TGF alpha precursor (proTGF alpha) is now shown to be due to microheterogeneity in the splicing of exons 2 and 3. This results from a tandem duplication of the acceptor CAG and gives rise to two alternate forms (159 and 160 amino acids) of the integral membrane precursor. Exon 6, which encodes the 3' untranslated region of TGF alpha mRNA, also encodes, on the opposite strand, a small (approximately 200 nucleotide) transcript whose sequence predicts an open reading frame of 51 amino acids. Expression of this latter transcript does not appear to be coregulated with that of TGF alpha mRNA. Primer extension and S1 nuclease analyses of authentic TGF alpha transcripts revealed two major and multiple minor 5' ends which span more than 200 base pairs of DNA in a G + C-rich region that lacks canonical CCAAT or TATA sequences. The 5' ends of six independently derived cDNAs localized to five different sites in this same region. Restriction fragments that overlap these transcription start sites and extend approximately 300 base pairs in the 5' direction faithfully promote transcription in vitro with HeLa cell nuclear extracts. In addition, they direct the expression of the bacterial chloramphenicol acetyltransferase gene in transient-transfection assays. PMID- 2325648 TI - Abnormal protein kinase C down regulation and reduced substrate levels in non phorbol ester-responsive 3T3-TNR9 cells. AB - The cell line TNR9 (E. Butler-Gralla and H. R. Herschman, J. Cell. Physiol. 107:59-67, 1981) in a Swiss 3T3 cell variant that expresses protein kinase C (PKC) but is mitogenically nonresponsive to the phorbol ester 12-O tetradecanoylphorbol-13-acetate (TPA). We have found that PKCs purified from variant and parental cells are identical as judged by kinase activity, protease mapping, and column chromatography. We analyzed cellular levels and subcellular location of PKC in TPA-treated 3T3 and TNR9 cells via immunoprecipitation of [35S]methionine-labeled protein and assay of immune-complex PKC kinase activity. TNR9 cells grew to higher densities than parental 3T3 cells. TNR9 cells at maximal density did not down regulate PKC in response to long-term TPA treatment. We compared the 80-kilodalton (kDa) PKC substrate phosphorylation in 3T3 and TNR9 cells by using two-dimensional gels and found that TNR9 cells treated with TPA for 30 min contained only 10 to 15% as much 32Pi associated with the 80-kDa as did parental cells. The TNR9 80-kDa substrate was present at reduced levels compared with the parental-cell 80-kDa substrate as judged by immunoblot and silver staining. Thus, the loss of mitogenic responsiveness to TPA in TNR9 cells is accompanied by resistance to TPA-mediated down regulation of PKC and reduced phosphosubstrate levels. PMID- 2325649 TI - Myosin light-chain 1/3 gene alternative splicing: cis regulation is based upon a hierarchical compatibility between splice sites. AB - The mechanisms involved in the selective joining of appropriate 5' and 3' splice sites are still poorly understood in both constitutive and alternatively spliced genes. With two promoters associated with different exons, the myosin light-chain 1/3 gene generates two pre-mRNAs that also differ by the use of a pair of internal exons, 3 and 4, that are spliced in a mutually exclusive fashion. When the promoter upstream from exon 1 is used, only exon 4 is included. If the promoter upstream from exon 2 is used, only exon 3 is included. In an attempt to understand the molecular basis for the mutually exclusive behavior of these two exons and the basis of their specific selection, a number of minigene constructs containing exons 3 and 4 were tested in a variety of homologous or heterologous cis and trans environments. The results demonstrate that the mutually exclusive behavior of myosin light-chain exons 3 and 4 and selection between the two exons are cis regulated and are affected by the nature of the flanking sequences. Both exons competed for the common flanking 5' and 3' splice sites. Flanking exons were found that favored inclusion into mature mRNA of exon 3, exon 4, both, or neither, suggesting a specific cooperative interaction between certain 5' and 3' splice sites. Thus, alternative splicing of myosin light-chain 1/3 pre-mRNAs is regulated in cis by a hierarchy of compatibilities between pairs of 5' and 3' splice sites. PMID- 2325651 TI - Efficient site-specific cleavage by RNase MRP requires interaction with two evolutionarily conserved mitochondrial RNA sequences. AB - RNase MRP is a site-specific endonuclease that processes primer mitochondrial RNA from the leading-strand origin of mitochondrial DNA replication. Using deletional analysis and saturation mutagenesis, we have determined the substrate requirements for cleavage by mouse mitochondrial RNase MRP. Two regions of sequence homology among vertebrate mitochondrial RNA primers, conserved sequence blocks II and III, were found to be critical for both efficient and accurate cleavage; a third region of sequence homology, conserved sequence block I, was dispensable. Analysis of insertion and deletion mutations within conserved sequence block II demonstrated that the specificity of RNase MRP accommodates the natural sequence heterogeneity of conserved sequence block II in vivo. Heterologous assays with human RNase MRP and mutated mouse mitochondrial RNA substrates indicated that sequences essential for substrate recognition are conserved between mammalian species. PMID- 2325650 TI - In vitro posttranslational modification of lamin B cloned from a human T-cell line. AB - Autoimmune diseases are characterized by spontaneously occurring autoantibodies which have proven to be useful reagents for the characterization of specific nuclear proteins. Using a monoclonal autoantibody (72B9) derived from a murine lupus strain, we have cloned a cDNA from the human T-cell line MOLT-4, which encodes nuclear lamin B. The identity of the encoded protein as lamin B was established by both biochemical and immunological criteria. Inspection of the deduced amino acid sequence of lamin B revealed the presence in coil 1B of the alpha-helical domain of a leucine heptad repeat region. Analysis of mRNA in HL60 and MOLT-4 cells, which express only lamin B, or HeLa cells, which express all three major lamins (A, B, and C), together with the comigration of in vitro translated product with isolated HeLa cell lamin B by two-dimensional gel electrophoresis, suggests that a single lamin B is expressed in mammalian somatic cells. In vitro translation with the cDNA clone revealed an EDTA-sensitive posttranslational modification which resulted in an increase in the apparent molecular weight to that equivalent to the native in vivo-synthesized lamin B protein. This in vitro modification included incorporation of a product of mevalonolactone and required an intact carboxy terminus. PMID- 2325652 TI - trans activation of gene expression by v-myb. AB - The v-myb oncogene causes acute myelomonocytic leukemia in chickens and transforms avian myeloid cells in vitro. Its product, p48v-myb, is a short-lived nuclear protein which binds DNA. We demonstrate that p48v-myb can function as a trans activator of gene expression in transient DNA transfection assays. trans activation requires the highly conserved amino-terminal DNA-binding domain and the less highly conserved carboxyl-terminal domain of p48v-myb, both of which are required for transformation. Multiple copies of a consensus sequence for DNA binding by p48v-myb inserted upstream of a herpes simplex virus thymidine kinase promoter are strongly stimulatory for transcriptional activation by a v-myb-VP16 fusion protein but not by p48v-myb itself, suggesting that the binding of p48v myb to DNA may not be sufficient for trans activation. PMID- 2325653 TI - The chicken lysozyme 5' matrix attachment region increases transcription from a heterologous promoter in heterologous cells and dampens position effects on the expression of transfected genes. AB - Matrix attachment regions (MARs) are DNA elements that dissect the genome into topologically separated domains by binding to a chromosomal skeleton. This study explored the putative influence of the MAR located 5' of the chicken lysozyme gene on expression of heterologous genes in heterologous cell systems. Expression of a construct with the chloramphenicol acetyltransferase (CAT) indicator gene controlled by the herpes simplex virus thymidine kinase promoter (TC) and a construct in which the same transcriptional unit is flanked by chicken lysozyme 5' MARs (MTCM) was assayed after stable transfection into rat fibroblasts. Median CAT activity per copy number in MTCM transfectants was elevated approximately 10 fold relative to that in TC transfectants. Total variation in normalized CAT activity decreased from more than 100-fold among TC transfectants to nearly 6 fold among MTCM transfectants. The steady-state level of transcripts and the relative rate of transcription were increased in MTCM transfectants, as shown by S1 nuclease and run-on transcription assays, respectively. The chicken lysozyme 5' MAR thus can confer elevated, less position-dependent expression on a heterologous promoter in cells of a different species by increasing the density of transcribing RNA polymerase molecules. MAR-mediated transcriptional enhancement suggests that MARs are important for gene expression and not just for DNA packaging. PMID- 2325654 TI - Testis-specific transcription initiation sites of rat farnesyl pyrophosphate synthetase mRNA. AB - A variety of rat tissues were screened at low stringency with a rat farnesyl pyrophosphate (FPP) synthetase cDNA. In testis, an FPP synthetase-related RNA was detected that was larger than the liver FPP synthetase mRNA and was present at very high levels comparable with liver FPP synthetase RNA levels obtained from rats fed diets supplemented with cholestyramine and mevinolin. Sequence analysis of testis cDNA clones, together with primer extension and S1 nuclease experiments, indicated that testis FPP synthetase transcripts contain an extended 5' untranslated region. The 5' extension contained one or two out-of-frame upstream ATGs, depending on the site of transcription initiation. Protein in vitro translation studies indicated that the extended 5' untranslated region may play a role in regulating the translation of the FPP synthetase polypeptide in rat testis. Southern blot analysis with a probe containing both testis and liver 5' untranslated sequences provided evidence that both liver and testis transcripts derive from the same gene. The data suggest that an upstream testis specific promoter results in the abundant production of FPP synthetase transcripts that are translated at low efficiency; another promoter functions in liver and other somatic tissues and directs the regulated synthesis of shorter discrete transcripts. PMID- 2325655 TI - A gene family for acidic ribosomal proteins in Schizosaccharomyces pombe: two essential and two nonessential genes. AB - We have cloned the genes for small acidic ribosomal proteins (A-proteins) of the fission yeast Schizosaccharomyces pombe. S. pombe contains four transcribed genes for small A-proteins per haploid genome, as is the case for Saccharomyces cerevisiae. In contrast, multicellular eucaryotes contain two transcribed genes per haploid genome. The four proteins of S. pombe, besides sharing a high overall similarity, form two couples of nearly identical sequences. Their corresponding genes have a very conserved structure and are transcribed to a similar level. Surprisingly, of each couple of genes coding for nearly identical proteins, one is essential for cell growth, whereas the other is not. We suggest that the unequal importance of the four small A-proteins for cell survival is related to their physical organization in 60S ribosomal subunits. PMID- 2325656 TI - A negative element involved in vimentin gene expression. AB - Vimentin is one member of the intermediate filament multigene family which exhibits both tissue- and developmental stage-specific expression. In vivo, vimentin is expressed in cells of mesenchymal origin. Previously, we identified both enhancer and promoter elements in the chicken vimentin gene which regulate gene expression in a positive manner. In this report, we have identified a 40 base-pair region at -568 base pairs between the proximal and distal enhancer elements which represses transcriptional activity. This silencer region can also repress the heterologous herpes simplex virus thymidine kinase promoter, which is comparable to the vimentin promoter. In addition, the element is able to function in a position- and orientation-independent manner, and the amount of repression is increased by multiple copies. Here we show by gel retardation assays and DNase I footprinting that this region binds a protein in nuclear extracts from HeLa cells. Southwestern (DNA-protein) blot analysis indicates this protein is approximately 95 kilodaltons in size. Moreover, protein distribution and activity mimic the expression pattern of vimentin during myogenesis, i.e., protein binding increases as vimentin gene expression decreases. The silencer region shares strong sequence similarity with 5'-flanking sequences found in both the human and hamster vimentin genes and with other characterized silencer elements, including the human immunodeficiency virus long terminal repeat, rat growth hormone, chicken lysozyme, and rat insulin genes. Thus, a negative element appears to bind a 95-kilodalton protein involved in regulating the tissue-specific expression of the chicken vimentin gene. PMID- 2325657 TI - Identification of mitogen-responsive ribosomal protein S6 kinase pp90rsk, a homolog of Xenopus S6 kinase II, in chicken embryo fibroblasts. AB - Antiserum raised against recombinant Xenopus ribosomal protein S6 kinase (rsk) was used to identify a 90,000-Mr ribosomal S6 kinase, pp90rsk, in chicken embryo fibroblasts. Adding serum to cells stimulated the phosphorylation of pp90rsk on serine and threonine residues and increased the activity of S6 kinase measured in immune complex assays. Xenopus S6 kinase II and chicken embryo fibroblast pp90rsk had nearly identical phosphopeptide maps. PMID- 2325658 TI - Developmentally regulated interactions of liver nuclear factors with the rat phosphoenolpyruvate carboxykinase promoter. AB - A sequential pattern of interactions of trans-acting factors in rat liver with the phosphoenolpyruvate carboxykinase promoter during late development was observed. A liver-enriched factor, possibly AF1, interacted with the promoter in fetal liver, whereas a factor with the characteristics of C/EBP bound the promoter after birth with the onset of the gene expression. PMID- 2325659 TI - RNA editing in the cytochrome b locus of the higher plant Oenothera berteriana includes a U-to-C transition. AB - RNA editing in the cytochrome b locus of Oenothera berteriana mitochondria modified a number of cytidine nucleotides to uridines, mostly altering codon identities. One nucleotide alteration involved a reverse modification changing a genomic thymidine to a cytidine in the cDNA sequence. The enzymatic editing activity in higher-plant mitochondria thus appears to be able to catalyze the interconversion of pyrimidines in both directions at specific nucleotides in the mRNA template. PMID- 2325660 TI - Identification of positive and negative regulatory regions controlling expression of the cartilage matrix protein gene. AB - A complex pattern of regulation of the cartilage matrix protein gene was revealed by transient expression experiments. A minimal promoter from positions -15 to +64 functioned in chondrocytes and fibroblasts. An enhancer located in the first intron exerted chondrocyte-specific stimulation on the minimal promoter activity. The same fragment, however, had a negative effect in fibroblasts. Between -334 and -15, a silencer was found which inhibited the gene expression driven from its homologous as well as heterologous promoters both in chondrocytes and fibroblasts. Additional positive and negative control regions were mapped further upstream of the promoter. PMID- 2325661 TI - A spermatozoa-associated factor regulates proenkephalin gene expression in the rat epididymis. AB - The gene encoding the opioid peptide precursor preproenkephalin is expressed at high levels in the initial segment of the adult rat epididymis. Expression is localized to principal cells, the secretory epithelial cells lining the epididymal duct. During development, epididymal proenkephalin mRNA levels show a pronounced increase at about 44 days of age, coincident with the initial entry of spermatozoa into the epididymal lumen. Hypophysectomy leads to a 60-fold decrease in epididymal proenkephalin mRNA levels. Testosterone replacement can prevent this decline in a manner consistent with an effect upon spermatogenesis. Castration studies demonstrate that a gonadal factor other than testosterone directly regulates epididymal proenkephalin expression, and the results of efferent duct ligation suggest that this factor must be supplied through an intact connection of the testis and epididymis. Proenkephalin mRNA levels in the epididymis correlate with the decline and reappearance of spermatozoa induced by the alkylating agent busulphan. Thus, the developmental profile of proenkephalin expression, coupled with the results of both surgical and pharmacological manipulations of the reproductive tract, indicate that spermatozoa, or a spermatozoa-associated factor, regulate proenkephalin gene expression in the epididymis. PMID- 2325662 TI - Direct analysis of CYP21B genes in 21-hydroxylase deficiency using polymerase chain reaction amplification. AB - Steroid 21-hydroxylase deficiency is the leading cause of impaired cortisol synthesis in congenital adrenal hyperplasia (CAH). We have studied the structure of the CYP21B gene in 30 unrelated CAH patients using the polymerase chain reaction (PCR) to differentiate the active CYP21B gene from its highly related CYP21A pseudogene. The PCR approach obviates the need to distinguish the CYP21A and CYP21B genes by restriction endonuclease digestion and electrophoresis before analysis with labeled probes. Furthermore, direct nucleotide sequence analysis of CYP21B genes is demonstrated on the PCR-amplified DNA. Gene deletion of CYP21B, gene conversion of the entire CYP21B gene to CYP21A, frame shift mutations in exon 3, an intron 2 mutation that causes abnormal RNA splicing, and a mutation leading to a stop codon in exon 8 appear to be the major abnormalities of the CYP21B gene in our patients. These mutations appear to account for 21-hydroxylase deficiency in 22 of 26 of our salt-wasting CAH patients. PMID- 2325663 TI - Stable expression of full-length and truncated bovine peptidylglycine alpha amidating monooxygenase complementary DNAs in cultured cells. AB - Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the production of alpha-amidated peptides from their glycine-extended precursors, a posttranslational modification often required for full biological activity. We have previously cloned cDNAs encoding a 108-kDa bovine PAM precursor. To confirm that this cDNA encodes a functional alpha-amidating enzyme and to begin to examine the structural requirements for the biosynthesis of an active PAM enzyme, we constructed expression vectors that placed the cDNA for either the full-sized enzyme or a form truncated at the carboxyl-terminal (and thus lacking the transmembrane domain) under the control of the mouse metallothionein-1 promoter. We used the resultant plasmids to transfect AtT-20 mouse anterior pituitary corticotrope cells and selected stable lines that expressed increased levels of PAM activity. Transfected cells in which expression from the metallothionein promoter had been induced had up to 15-fold higher levels of PAM mRNA and up to 7.5-fold higher levels of PAM activity than wild-type cells. The PAM activity in the transfected cells shared many enzymatic characteristics with PAM-B, a 38-kDa soluble form of PAM purified from bovine neurointermediate pituitary. These included copper- and ascorbate-dependent activity, an alkaline pH optimum for the peptide substrate D-Tyr-Val-Gly, similar affinities for several other synthetic substrates, and comparable apparent size during gel filtration. Compared to extracts of wild-type cells, extracts from transfected cells showed increased production of five different amino acid alpha-amides. These data indicate that a single enzyme can act on a variety of peptide substrates, and that the full structure of the PAM precursor is not necessary during biosynthesis for expression of active PAM enzyme. PMID- 2325664 TI - Estradiol decreases retention of rhodamine 123 fluorescence in GH4C1 pituitary tumor cells. AB - Rhodamine 123 is a lipophilic cationic fluorescent dye that localizes in mitochondria. We found that 17 beta-estradiol changes the ability of GH4C1 cells, clonal rat pituitary tumor cells, to retain rhodamine 123. Cells incubated with 10 micrograms/ml rhodamine 123 for 30 min at 37 C took up about equal amounts of rhodamine 123, as determined by fluorescence microscopy, regardless of whether they had been treated with estradiol. After three 5-min washes at 37 C, cells treated with 1 nM estradiol for 7 days before incubation with rhodamine 123 had lost more fluorescence than untreated cells. We further characterized the effect by flow cytometry. The difference in fluorescence between control and treated cells ranged from 50- to 500-fold. The effect of estradiol was maximal at 10(-10) M and took a week to develop fully. The effect is specific for estradiol, because estradiol and diethylstilbestrol reduced retention of rhodamine 123 fluorescence at 10(-10) M, but the same concentrations of dihydrotestosterone, progesterone, dexamethasone, and cholesterol did not. To test if the effect on rhodamine 123 fluorescence was caused by activation of the multidrug resistance transport system, we examined the effect of estradiol on the retention of daunomycin, a known substrate of the transport system. Estradiol treatment caused a 3-fold decrease in daunomycin fluorescence. We isolated clones resistant to estradiol induced loss of rhodamine 123 fluorescence by flow cytometry and found that two clones still showed an estradiol-induced decrease in daunomycin fluorescence equivalent to that of the parent line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325665 TI - Local regulation within the female reproductive system and upon embryonic implantation: identification of cells expressing proenkephalin A. AB - The detection of proenkephalin A (PEA) mRNA and encoded peptides in various regions of the female reproductive system raised the possibility that opioid peptides might act as local regulators within this system. Assignment of a specific role for locally synthesized enkephalins has been hampered, however, by the unknown identity of the cells that produce PEA. Using in situ hybridization analysis we have now identified the cell types that express PEA mRNA in the reproductive system of female mice. In the ovary, PEA mRNA was localized primarily in theca cells of preovulatory follicles, and to a lesser extent, in follicular granulosa cells. In the oviducts, where PEA mRNA is most abundant, expression was confined to the secretory and ciliated epithelium of the mucosa. In the uterus, the site of PEA mRNA expression was the deep glandular layer of the endometrium. When pregnancy ensues, and upon decidual transformation, PEA expression by the same uterine cells was dramatically elevated. Elevated levels of PEA mRNA were detected predominantly in the vicinity of the implantation site, suggesting that signaling by the implanted embryo play a role in stimulating PEA expression. Based on these results, possible physiological roles for PEA-encoded peptides as autocrine/paracrine regulators within the female reproductive system are suggested. PMID- 2325666 TI - A second thyroglobulin messenger RNA species (rTg-2) in rat thyrocytes. AB - A 0.95-kilobase (kb) thyrocyte RNA, initially detected in our 1B-6 subclone of Fisher rat thyrocytes (FRTL-5) using an oligonucleotide probe complementary to the 5' end of rat thyroglobulin (Tg) mRNA, was also detected in cultured thyrocytes of the Wistar rat (WRT cells) and in freshly isolated normal rat thyroid tissue. This transcript was thyroid specific and as abundant as the previously characterized 9.0-kb Tg mRNA in the cultured thyroid cells under the growth conditions employed. The smaller RNA (designated rTg-2 mRNA) was cytoplasmic, polyadenylated, and regulated by TSH. Preliminary characterization with several oligonucleotide probes showed that rTg-2 shared coding information present at the 5', but not the 3', end of the 9.0-kb Tg mRNA. Sequencing of the cloned rTg-2 cDNA showed that it was homologous to human and other higher vertebrate Tg cDNAs at its 5' coding end, but contained additional nonhomologous coding and noncoding sequences at the 3' end. The junction between the shared and unique sequences in rTg-2 mRNA occurred at the exon-5/intron-5 boundary in the Tg gene. This smaller transcript has not previously been reported and encodes elements known to be of structural and functional significance in the 330-kD Tg monomer. A putative polypeptide product from rTg-2 mRNA may play an important role in thyroid function and thyroid autoimmunity. PMID- 2325667 TI - Autologous down-regulation of androgen receptor messenger ribonucleic acid. AB - Autoregulation of androgen receptor (AR) mRNA was investigated using Northern blot analysis with AR cDNA fragments as probes. The amount of AR mRNA increased 2 to 10-fold with androgen withdrawal and decreased below control levels after androgen stimulation in rat ventral prostate, coagulating gland, epididymis, seminal vesicle, kidney, and brain, and in a human prostate cancer cell line, LNCaP. In rat ventral prostate, AR mRNA increased 2- to 3-fold within 24 h after castration and remained elevated for 4 days. Treatment with testosterone propionate beginning 24 h after castration reduced ventral prostate AR mRNA 4 fold within 8 h of androgen replacement. Administration of estradiol 24 h after castration had no significant effect on prostatic AR mRNA. Androgens, including testosterone and the synthetic androgen methyltrienolone (R1881), or the antiandrogen cyproterone acetate down-regulated AR mRNA in vitro in LNCaP cells, whereas estradiol was without effect. Administration of testosterone propionate to rats with androgen insensitivity did not decrease AR mRNA. Down-regulation of AR mRNA by androgen is therefore a receptor-mediated process which occurs in vivo in rat tissues that differ in androgen responsiveness and in cultured human prostate cells. PMID- 2325668 TI - Structural and regulatory analysis of the male-specific rat liver cytochrome P 450 g: repression by continuous growth hormone administration. AB - Complementary DNA clones encoding the male-specific rat liver cytochrome P-450 g have been isolated by cross-hybridization with sequences from the female-specific rat liver cytochrome P-450 15 beta. Tissue distribution analysis indicates the liver as the organ with major expression of this cytochrome P-450 gene. Minimal P 450 g expression was also detected in prostate, kidney, heart, and brain. A developmental analysis reveals liver expression in the 8-week-old male and to a lesser extent in the 4-week-old male, but no detectable expression is seen in females of these ages or in 1- and 2-week-old rats from both sexes. Hypophysectomy of female rats dramatically increases hepatic expression of P-450 g, whereas continuous GH administration represses hepatic expression in male or female hypophysectomized rats. In similarity to P-450 15 beta and P-450 16 alpha, therefore, the cytochrome P-450 g gene in liver is GH regulated. PMID- 2325669 TI - Thymosin beta 4 is expressed in ROS 17/2.8 osteosarcoma cells in a regulated manner. AB - The differential expression of mRNAs between the closely related rat osteosarcoma cell lines ROS 17/2.8 and ROS 25/1 was used to identify genes whose expression is associated with the osteoblast phenotype. Thymosin beta 4 cDNA was cloned from an ROS 17/2.8 complimentary DAN library on the basis of its differential hybridization with radiolabeled cDNA prepared from ROS 17/2.8 and ROS 25/1 cells. Northern blot analysis confirmed that thymosin beta 4, hitherto a putative immunodulatory hormone, was indeed differentially expressed. Steady state mRNA levels were severalfold higher in ROS 17/2.8 cells exhibiting an osteoblast-like phenotype, compared with the less osteoblast-like ROS 25/1. Thymosin beta 4 transcripts were also detected in rat UMR 106 osteosarcoma cells and in intact neonatal and fetal rat calvaria. Sequence analysis of the cDNA indicated that thymosin beta 4 transcripts may arise by processing at a more distal polyadenylation signal. Treatment of ROS 17/2.8 cells with dexamethasone increased, while addition of 1,25-dihydroxyvitamin D3 decreased thymosin beta 4 mRNA. The phenotype-dependent expression in the ROS cells and the response to steroid hormone suggest that thymosin beta 4 expression contributes to the osteoblast phenotype. PMID- 2325670 TI - Localization of inhibin/activin subunit mRNAs within the primate ovary. AB - In order to gain further understanding of the physiology of inhibin and activin in the primate, the expression of inhibin/activin subunit mRNAs in the monkey ovary was examined by in situ hybridization. Granulosa cells of small antral follicles were found to express mRNA for the beta B subunit, which decreased to undetectable levels in dominant follicles. In contrast, expression of alpha and beta A subunit mRNAs was detected in granulosa cells of dominant follicles and in corpora lutea, but not in small antral follicles. These results indicate that the expression of the beta A and beta B subunits is differentially regulated during the growth and development of ovarian follicles in the monkey. PMID- 2325671 TI - Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. AB - Previous studies have indicated that the concentration of circulating insulin like growth factor-I (IGF-I) declines in young growing rats that have been fasted or maintained on a protein-deficient diet. To investigate the molecular mechanism(s) by which IGF-I levels are regulated by nutrition, we measured the levels of IGF-I mRNA in 6-week-old male control rats fed ad libitum, rats fasted for 24, 48, or 72 h, and rats fasted for 48 or 72 h and then refed for 24 h. The abundance of several IGF-I mRNA species (8.0, 4.0, 1.7, and 1.0 kilobases) decreased in the fasting animals and rebounded after 24 h of refeeding, although not to the initial control levels. The 1 kilobase IGF-I mRNA species exhibited a 43% decrease after 24 h of fasting, a 76% decrease after 48 h of fasting, and an 82% decrease after 72 h of fasting. Hepatic GH receptor mRNA also decreased in fasting rats. This indicates that the GH receptor down-regulation that occurs in fasting is accompanied by and probably at least partly caused by a decline in GH receptor mRNA. The magnitude and kinetics of the decline in GH receptor mRNA were similar to the magnitude and kinetics of the decline in IGF-I mRNA, suggesting that the two mRNAs may be regulated by a similar mechanism. There was no significant change in the levels of liver beta-actin or serum albumin mRNA under the same conditions, indicating that the regulation of IGF-I and GH receptor mRNA was specific. In addition, the levels of brain IGF-II, beta-actin, and alpha tubulin mRNAs were not significantly changed by fasting. To further elucidate the molecular mechanism for regulation of hepatic IGF-I mRNA, nuclear transcription elongation assays were performed using nuclei isolated from the liver of control rats, rats fasted for 72 h, and fasted-refed rats. There was considerable animal to-animal variability in IGF-I gene transcription within each group. The mean level of IGF-I gene transcription was lower in the fasting animals than in the fed controls. However, this decrease was not statistically significant, and the magnitude of the decrease did not account for the 79% decrease in total IGF-I mRNA. These results suggest that IGF-I mRNA is regulated at least partly at the posttranscriptional level. PMID- 2325672 TI - Movement disorders in mitochondrial myopathies. A study of nine cases with two autopsy studies. AB - Of 85 consecutive patients with mitochondrial myopathy, 29 had clinically significant central nervous system involvement. Nine of these had movement disorders that included dystonia, chorea, parkinsonism, and myoclonus. Autopsy studies of one patient with ataxia, dementia, and parkinsonism followed by dystonia showed the features of olivopontocerebellar atrophy with additional degenerative changes in the basal ganglia. Postmortem in a further case with myoclonus, deafness, muscle weakness, retinopathy, and ataxia showed symmetrical mineralisation of the striatopallidodentatal system. PMID- 2325673 TI - Primary writing tremor. A form of focal dystonia? AB - Five patients exhibited severe tremor in the upper extremity, primarily when attempting to write or draw. Electromyography was performed to determine the patterns of muscle activity that were responsible for this tremor. Tremor was measured with an accelerometer and with a digitizing tablet. Two patients had postural tremor that was indistinguishable from mild, high-frequency essential tremor. All patients exhibited a severe 5-7-Hz tremor during the acts of writing and drawing. Muscles throughout the affected extremity exhibited rhythmic 5-7-Hz bursts of motor unit discharge, and the average level of motor unit activity was tonically increased in antagonistic muscles. This abnormal coactivation of antagonistic muscles produced subtle dystonic posturing of the affected limb that was overshadowed by severe tremor. Electromyography was useful in confirming the coexistence of tremor and dystonia in our patients. The nonspecificity of dystonia and postural tremor must be considered when discussing the nosology and pathophysiology of primary writing tremor. PMID- 2325674 TI - Psychogenic dyskinesias in patients with organic movement disorders. AB - The association of psychogenic neurological features with organic neurological disease is commonly acknowledged. However, the occurrence of psychogenic dyskinesias in patients with underlying organic movement disorders is not well recognized. Six cases of psychogenic dyskinesias complicating preexisting organic movement disorders are described. This possibility must be carefully considered and excluded before an unusual movement disorder can be considered entirely psychogenic. PMID- 2325675 TI - Gaze-evoked involuntary movements. AB - Voluntary gaze may evoke a number of neurological phenomena such as vertigo, tinnitus, blepharoclonus, eyelid nystagmus, "facial nystagmus," involuntary laughter, and seizures. We report two patients in whom eccentric gaze evoked facial twitching and arm movement. Electroencephalograms remained unchanged during these movements. The pathogenesis of these movements is unclear but may involve ephaptic transmission. PMID- 2325676 TI - Mood changes and "on-off" phenomena in Parkinson's disease. AB - Ten patients with idiopathic Parkinson's disease and motor fluctuations were rated for mood changes during discrete "off," "on," and "on with dyskinesia" periods. The Profile of Mood States and visual analogue scales were used. Significant changes in mood and anxiety were found to parallel changes in motor fluctuations. One patient rated his moods as consistently improving from the "off" state to the "on" state and finally to the "on with dyskinesia" state, a finding that is consistent with concomitant central dopaminergic changes. All other patients showed moods that improved significantly from the "off" state to the "on" state but then worsened significantly in the "on with dyskinesia" state, a finding that is consistent with the fact that patients feel worse when impaired by dyskinesias. It is suggested that these results argue for multiple etiologies of depression in Parkinson's disease. The literature on dopamine and depression in Parkinson's disease is briefly reviewed and the opportunity provided by "on off" phenomena to study the effect of dopamine on mood changes is discussed. PMID- 2325677 TI - Neurosurgical treatment of severe obsessive-compulsive disorder associated with Tourette's syndrome. AB - We describe two patients with Gilles de la Tourette's syndrome (TS) and disabling obsessive-compulsive and ritualistic behaviors who underwent bilateral radiofrequency anterior cingulotomy. Both achieved a limited but sustained improvement in behavioral symptoms and overall functional abilities. Our observations indicate involvement of limbic structures in this disorder. The procedure should be considered for patients with TS complicated by resistant obsessive-compulsive disorder. PMID- 2325678 TI - A pilot study of risk factors for dementia in Parkinson's disease. AB - To determine whether the risk factors for dementia in idiopathic Parkinson's disease (IPD) are similar to the risk factors for Alzheimer's disease, we conducted a case-control study of potential risk factors. A structured interview was administered to surrogates of 17 demented subjects with IPD and 54 nondemented subjects. Two factors emerged as possible risks for dementia. Demented patients were older than nondemented patients, although the duration of symptoms was similar. A family history of dementia was present in 30% of the demented group and 5.6% of the nondemented group. Dementia was most often reported among siblings. No difference was seen in toxic and occupational exposure, personal habits, or medical or surgical illnesses. We conclude that dementia in IPD shares some common risk factors with Alzheimer's disease. Efforts to assess the contribution of genetic susceptibility or shared environmental influences may clarify the relationship between these two diseases. PMID- 2325680 TI - Neuroleptic malignant syndrome treated with subcutaneous lisuride infusion. AB - A schizophrenic patient developed a characteristic clinical picture of neuroleptic malignant syndrome (NMS) while admitted to the hospital during an exacerbation of his psychiatric symptoms. Oral treatment of the NMS with bromocriptine (7.5 mg/day) or levodopa/carbidopa (125/12.5 mg) provoked intense vomiting in spite of domperidone (60 mg/day), which led to their discontinuation. In view of the deterioration of the symptoms, treatment was begun with lisuride (1-2 mg/24 h) subcutaneously. An obvious improvement was shown in 24 h, but levodopa/carbidopa (125/12.5 mg t.d.s. orally) had to be added later to achieve complete resolution of the NMS. During the recovery phase, while being treated with subcutaneous lisuride infusion and levodopa (p.o.), the patient presented with confusion, agitation, and hallucination. Lisuride infusion was stopped and levodopa was continued until complete resolution of the NMS. This case indicates that parenteral administration of lisuride or other dopamine agents such as levodopa (i.v.) or apomorphine (s.c.) may be considered an effective and practical way of treating NMS, particularly when the patient's condition makes it difficult or impossible to use other dopaminergic drugs by the oral route. PMID- 2325679 TI - Exaggerated startle reflexes in an elderly woman. AB - A 76-year-old woman with a 5-year history of excessive startle is reported. Electrophysiological recordings were made of muscle activation after acoustic and proprioceptive stimulation. The findings are discussed in relation to current knowledge of the startle reflex and classification of startle syndromes. It is concluded that this patient is best regarded as having a pathological exaggeration of the normal startle reflex rather than other causes of stimulus sensitive muscle jerks. PMID- 2325681 TI - A movement disorder as a presenting feature of recurrent hypoglycaemia. PMID- 2325682 TI - Dystonia and cerebellar ataxia. PMID- 2325683 TI - Parkinson's disease: a reduced ability to shift to a new grouping if not prompted or guided. PMID- 2325684 TI - Autoimmune etiology for cranial dystonia. PMID- 2325685 TI - Paroxysmal hypnogenic dystonia responsive to phenytoin. PMID- 2325686 TI - Clinical evaluation of bidirectional torticollis. PMID- 2325687 TI - Tardive akathisia. PMID- 2325688 TI - Volitional control of palatal myoclonus. PMID- 2325689 TI - Posttraumatic tic disorder. PMID- 2325691 TI - Human lymphocyte proliferation kinetics in Hanks' BSS supplemented with autologous plasma and in synthetic medium. AB - Human lymphocyte proliferation kinetics was studied in different culture conditions including synthetic medium, Hanks' BSS and Hanks' supplemented with autologous plasma at several culture times. Even though mitotic indices (MI) were low, lymphocytes were able to divide for a few cycles in BSS alone, with a cycling time of around 24 h. Similar cell proliferation patterns with similar MIs, replication indices and cell cycle times of approximately 12 h were obtained with RPMI 1640 and with autologous plasma-supplemented BSS, although lymphocytes exhibited a more uniform MI distribution curve in synthetic medium. The findings mentioned above suggest that Hanks' with autologous plasma may represent a suitable and inexpensive culture condition to avoid undesirable side effects related to synthetic media and heterologous sera, for diagnostics as well as research cytogenetics. PMID- 2325690 TI - Immunodetection of DNA-protein crosslinks by slot blotting. AB - Ultraviolet light, formaldehyde, cis-diamminedichloroplatinum(II), chromate (Cr6+), or chromium chloride (Cr3+) under the appropriate conditions caused the formation of DNA-protein crosslinks in intact Chinese hamster ovary (CHO) cells or in cell nuclei. The DNA-protein crosslinks were isolated, applied to nitrocellulose filters, and reacted with antibodies to nuclear proteins. An antiserum to a 97-kD nuclear protein detected p97-DNA complexes in CHO nuclei and cell cultures treated with UV light, cis-Pt and formaldehyde. Exposure to Cr3+ induced p97-DNA crosslinks only in isolated nuclei, while chromate (Cr6+) treatment resulted in significant crosslink formation only in intact cells. Analysis of western blots with the p97 antiserum indicated that crosslinks induced by formaldehyde or ultraviolet light required DNAase I digestion of DNA for migration of the p97 complexes into the gel. In contrast, the 97-kD antigen from the metal-induced crosslinks was released from DNA and resolved in the gel when 2-mercaptoethanol was included in the electrophoresis sample buffer. Assay of slot blots with an antihistone monoclonal antibody indicated that formaldehyde, but not cis-Pt or chromate, crosslinked histones to the DNA. These results illustrate the utility of immuno-slot blots in detecting and characterizing DNA-protein complexes induced by diverse chemical and physical agents. PMID- 2325692 TI - The relation between induced reciprocal translocations and cell killing of mouse spermatogonial stem cells after combined treatments with hydroxyurea and X-rays. AB - The induction of reciprocal translocations in mouse spermatogonial stem cells, visualised in dividing primary spermatocytes, was studied after combined treatments with hydroxyurea (250 and 500 mg/kg) and X-rays (6, 8 and 9 Gy). The time intervals between the 2 treatments were 16 h (leading to extremely high cell killing) and 48 h (giving rise to less killing than irradiation alone). Comparison of the observed frequencies of translocations with reported data on stem cell killing (de Ruiter-Bootsma and Davids, 1981) show that the ratio between the probabilities that a radiation-induced basic lesion kills a cell or produces a translocation, theoretically calculated by Leenhouts and Chadwick (1981) to be about 10, can indeed be confirmed experimentally. PMID- 2325693 TI - 1-Chloromethylpyrene: a reference skin sensitizer and genotoxin. AB - 1-Chloromethylpyrene (1-CMP) has been evaluated as a model mutagen and toxin related to the ultimate electrophiles derived from benzo[a]pyrene and 1 nitropyrene. It was mutagenic to Salmonella (greater than 100 pg/plate) and exceptionally reactive to DNA when assessed by the 32P-postlabelling technique. 1 CMP was inactive in a mouse bone micronucleus assay when administered by gavage, probably due to hydrolysis, whose kinetics have been studied (t1/2 approximately 23 min at 37 degrees C). However, as expected, it was a potent skin toxin as determined by its activity as a mitogen to mouse skin and its contact allergenicity, as determined using the local lymph node proliferative assay. It is concluded that 1-CMP will probably be a potent human skin carcinogen and contact allergen. PMID- 2325694 TI - Suppressing effects of vanillin, cinnamaldehyde, and anisaldehyde on chromosome aberrations induced by X-rays in mice. AB - X-ray-induced chromosome aberrations were suppressed when vanillin, cinnamaldehyde, or p-anisaldehyde was given orally to mice after X-ray irradiation. Chromosome aberrations were monitored by the occurrence of polychromatic erythrocytes with micronuclei in bone marrow cells. The frequency of micronuclei was depressed about 55-60% without toxicity of the test compounds to the bone marrow. PMID- 2325695 TI - Mutagenic activity of metabolites contained in the plasma of Sprague-Dawley rats treated with cyclophosphamide. AB - In the present study we have tried to add some new results to those data previously obtained by Natarajan et al. (1983) and Darroudi and Natarajan (1985), where they have used in vivo metabolization and cytogenetic testing for in vitro analysis of xenobiotic compounds. Sprague-Dawley rats were treated intraperitoneally with 2.5, 5.0, 10.0 and 20.0 mg/kg b.w. of cyclophosphamide in order to obtain plasma containing active metabolites of the drug. The mutagenic activity was assessed by estimating the frequencies of sister-chromatid exchanges (SCE) in human and rat lymphocytes. No influence of animal age was observed on the metabolism of cyclophosphamide, which could be detected by SCE analysis. The increase in SCE frequencies in both human and rat lymphocytes was dependent on the doses applied. SCE frequencies are highly variable among individuals, showing statistically significant differences. The same effect, but to a lesser extent, was also found in rats. Rat lymphocytes can be assumed to be good biological material for chemical mutagenesis, as the animals can be maintained at almost constant experimental conditions. However, rat lymphocytes do not grow well in in vitro cultures. These data contribute to the preview proposal that combining metabolism in vivo and chromosome SCE analysis in vitro can be regarded as an important and very sensitive system to detect the mutagenic activity of low-dose exposure to chemical compounds requiring metabolic activation. PMID- 2325696 TI - Nerve conduction studies in the superficial radial nerve entrapment syndrome. AB - This report reviews the syndrome of entrapment of the superficial branch of the radial nerve (SBRN) in the forearm, and electrodiagnostic techniques to aid in diagnosis are presented. Normal mean radial sensory conduction in the forearm was found to be 61.4 +/- 3.1 m/sec. Three patients are presented. In two of these comparison of conduction in the SBRN to the lateral antebrachial cutaneous nerve (LACN) and contralateral SBRN was abnormal, whereas the absolute SBRN conduction appeared normal. Normal LACN-SBRN difference in the same arm was 1.9 +/- 1.6 m/sec, with a range of 0-7.0 m/sec; mean SBRN difference in opposite arms of the same subject was 1.8 +/- 1.6 m/sec. PMID- 2325697 TI - Are there motor fibers in the sural nerve? AB - A case of anomalous innervation of the abductor digiti quinti of the foot (ADQ) via the sural nerve is described. A muscle action potential from the ADQ could be elicited by stimulation of both the sural and the posterior tibial nerves. PMID- 2325698 TI - Paramyotonia congenita or hyperkalemic periodic paralysis? Clinical and electrophysiological features of each entity in one family. AB - The nosological distinction between paramyotonia congenita (PC) and hyperkalemic periodic paralysis (HPP) continues to generate debate. Recently, electrophysiological signs thought to be specific for each entity have been described and have been used to bolster the argument that the two disorders are distinct. We report a particularly instructive family wherein individual members had clinical features of either PC or HPP and electrophysiological features of both. We suggest that PC and HPP represent part of the spectrum of a single genetic disorder. Evoked response testing, with exercise and cold provocation, may be useful in determining the physiologic pattern that predominates in any one individual. PMID- 2325699 TI - Excessive plasma K+ increase after ischemic exercise in myotonic muscular dystrophy. AB - Changes in plasma electrolyte levels upon ischemic forearm exercise were studied in myotonic muscular dystrophy (MyD) patients, disease control groups, and healthy volunteers. Significant differences were observed in the pH and the concentrations of creatine kinase and Na+ before exercise between healthy volunteers and MyD patients. In comparison with healthy volunteers a lower pH and higher concentrations of both CK and Na+ were found in MyD patients. The concentrations of K+, inorganic phosphate, lactate, and ammonia increase upon exercise in all groups. The mean increase in plasma K+ for healthy volunteers amounted to 0.8 mM (= 23%). In MyD patients a significantly higher increase in plasma K+ was found [mean 2.2 mM (= 65%)]. No abnormal release of K+ from muscular tissue was found in the disease control groups. Data on the postexercise increase in the concentration of other muscular constituents such as creatine kinase, inorganic phosphate, or creatine exclude the possibility of a generally increased membrane permeability in MyD. The abnormally high increase of plasma K+ upon muscular exercise seems to be specific for MyD and may be related to the biochemical defect in this disease. PMID- 2325700 TI - Calf enlargement in hereditary motor and sensory neuropathy. AB - Six members originating from two families with hereditary motor and sensory neuropathy (hypertrophic and neuronal types) were noted to have enlarged calf muscles. Muscle computed tomography revealed that muscle enlargement in the propositus of the family with the hypertrophic type of HMSN was due to an increase in muscle and/or connective tissue. Computed tomography of the legs of the propositus of the family with the neuronal type of HMSN showed infiltration of the medial head of the gastrocnemius muscle by adipose tissue. PMID- 2325701 TI - Far-field and cortical somatosensory evoked potentials in motor neuron disease. AB - We examined median somatosensory evoked potentials (SEPs) in 26 patients with sporadic motor neuron disease (MND). SEPs were recorded with multiple scalp derivations, using both the midfront and the earlobe as references for each subject. Central conduction time (CCT) was abnormal in three patients, but only when using the midfront reference. Moreover, an exclusive alteration of the early prerolandic potentials (absent or delayed P20 and/or P22) was noted using the earlobe reference in amyotrophic lateral sclerosis and in progressive bulbar palsy (54% and 50% of patients, respectively) but not in progressive muscular atrophy. These findings correlated with clinical evidence of upper motor neuron signs and with the severity of the disease. In agreement with recent views regarding the sources of the early anterior cortical responses, neuronal loss in the motor cortex may be considered as affecting the generator sites of these potentials. PMID- 2325702 TI - Autonomic function and unmyelinated fibers in chronic inflammatory demyelinating polyradiculoneuropathy. AB - Because autonomic function may be abnormal in some demyelinating peripheral neuropathies, it has been studied with a number of noninvasive and invasive tests in 14 patients with chronic inflammatory demyelinating polyradiculoneuropathy. There were abnormalities of the 30:15 ratio in 3 patients and an abnormal thermoregulatory sweat test in 5 patients. These findings are indicative of mild parasympathetic and sympathetic dysfunction. Minor pathological changes in unmyelinated fibers were demonstrated on morphometric examination of sural nerves of 10 patients. PMID- 2325703 TI - The effect of two novel analogues of antimycin A on oxygen consumption and survival of filarial nematodes in vitro. AB - The effects of two novel analogues of antimycin A (BWA466C and BWA728C) on filarial oxygen consumption, energy generation and survival were investigated in vitro. For comparison, incubations were performed with a range of mitochondrial respiration inhibitors. All compounds tested (rotenone, antimycin A, KCN, oligomycin, CCCP, rafoxanide, BWA466C and BWA728C) inhibited oxygen uptake. The two analogues were less potent than antimycin A at impairing respiration of either filariae or beef heart submitochondrial particles. However, the two compounds affected motility and were lethal in vitro. Although the analogues affected oxygen uptake similarly to antimycin A itself, the levels of ATP were significantly lower than those noted in the presence of antimycin A. Glucose consumption and lactate output were markedly reduced by BWA466C and BWA728C. Glucose transport (measured as 2-deoxy-[2,6-3H]glucose) was reduced after treatment with BWA728C. It is likely that a combination of the effects on glucose transport and inhibition of oxidative pathways of carbohydrate metabolism may lead to worm death in vitro. PMID- 2325704 TI - A molecular karyotype of Eimeria tenella as revealed by contour-clamped homogeneous electric field gel electrophoresis. AB - DNA from sporozoites of Eimeria tenella was resolved by pulsed field gel electrophoresis into nine chromosomal bands. Some bands of this molecular karyotype contained more than one chromosome as determined by the relative intensity of both staining with ethidium bromide and hybridisation to an E. tenella telomeric probe. Haploid forms of the parasite must be presumed to contain at least 12 chromosomes. The two smallest chromosomes were about 1.1 and 1.4 megabases. Most chromosomes were in excess of 3 Mb with the largest over 5 Mb as determined by comparison with the co-migration of chromosomes from Schizosaccharomyces pombe. A 5S ribosomal gene probe hybridised to a single chromosomal band. PMID- 2325705 TI - Fatty acid and sterol metabolism of cultured Trichomonas vaginalis and Tritrichomonas foetus. AB - Trichomonas vaginalis and Tritrichomonas foetus grown in a fetal calf serum-based culture medium, contained as major lipids (i.e., greater than 10% of total) cholesterol, phosphatidylethanolamine and phosphatidylcholine. T. vaginalis also contained sphingomyelin and T. foetus glycophosphosphingolipids. The culture medium contained (greater than 10%) cholesterol, phosphatidylethanolamine, phosphatidylcholine, sphingomyelin and lysophosphatidylcholine. The fatty acyl groups of these major lipids of the trichomonads and the culture medium were similar. Those present in amounts greater than 5% of the total fatty acyl groups for a given lipid were myristic, palmitic, hexadecaenoic, stearic, oleic, linoleic, arachidonic and docosahexaenoic. When the trichomonads were exposed to radiolabeled lipids and lipid precursors, [14C]-labeled acetate and potential acetate precursors (glucose, threonine) were poorly incorporated and failed to label the fatty acyl groups of the trichomonad lipids. [14C]-labeled, C12-C22 saturated and unsaturated fatty acids were incorporated, unaltered, into phosphoglycerides and sphingolipids (sphingomyelin and glycophosphosphingolipids), but not into cholesteryl esters or triacylglycerols. Phosphoglycerides were preferentially labeled with unsaturated fatty acids and sphingolipids with saturated ones. This information inferred that the trichomonads: 1) were unable to biosynthesize fatty acids de novo, 2) took up unesterified fatty acids from the culture medium and used them in phosphoglyceride and sphingolipid biosynthesis and/or turnover, 4) did not use unesterified fatty acids in the biosynthesis or turnover of cholesteryl esters or triacylglycerols. Phosphatidylcholine and phosphatidylethanolamine, with [14C]labeled fatty acyl groups, and sphingomyelin, with 14C-labeled choline, were incorporated by the trichomonads. The phospholipids strongly labeled phosphoglycerides and sphingolipids, but not triacylglycerols, while the radioactivity of sphingomyelin [14C]choline remained associated solely with trichomonad sphingomyelin. Triacylglycerol, with 14C-labeled fatty acyl groups, was also incorporated, and labeled phosphoglycerides and sphingolipids. The results of those experiments suggested that trichomonads: (1) could take up culture medium phospholipids and triacylglycerols; (2) actively deacylated and reacylated phospholipids, but not triacylglycerols; (3) hydrolyzed exogenous triacylglycerols and used their fatty acyl groups for phospholipid acylations. Radiolabeled acetate, mevalonate and squalene were not incorporated into trichomonad cholesterol or cholesteryl esters. [14C]Cholesterol was incorporated unaltered, but was not esterified.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2325706 TI - Characterisation of Sm20, a 20-kilodalton calcium-binding protein of Schistosoma mansoni. AB - A cDNA clone encoding part of a 20-kDa antigen of Schistosoma mansoni (Sm20) has been isolated. The amino acid sequence of this antigen, as predicted from the sequence of the cDNA, has significant homology to the family of calcium binding proteins which include calmodulin, troponin C and the light chain of myosin. Although we have been unable to show any immunological cross-reactivity between Sm20 and calmodulins from a range of other species, we have verified that Sm20 is a functional calcium binding protein. Sm20 is encoded by a small multigene family and is expressed in schistosomula and adult worms but not in eggs. The 20-kDa nascent polypeptide appears to be post-translationally modified to give a 38-kDa species. Sm20 is present in preparations of tegumental membranes and is easily removed from intact schistosomula by detergent treatment, suggesting that it is associated with the tegument. However, the cloned portion does not appear to be exposed on the surface. PMID- 2325707 TI - Specific interaction of benzimidazole anthelmintics with tubulin: high-affinity binding and benzimidazole resistance in Haemonchus contortus. AB - The specific (high-affinity) binding of tritiated benzimidazole [(3H]BZ) anthelmintics-mebendazole [(3H]MBZ) and oxibendazole [(3H]OBZ) to, and the specific displacement (inhibition) of these radioligands by unlabelled BZs (oxibendazole, mebendazole, oxfendazole, albendazole, fenbendazole and thiabendazole) from crude tubulin extracts prepared from thiabendazole (TBZ) susceptible (S) or TBZ-resistant (R) strains of adult Haemonchus contortus, have been examined. The most striking difference between R and S was that the drug specifically bound at infinite ligand concentration (Bmax), was markedly reduced for the R strain, with no apparent change in association constant (Ka). Thus, resistance was associated with a loss of high-affinity receptors. TBZ-resistance was not associated with a change in low-affinity binding. There was a greater loss of high affinity receptors for [3H]OBZ than for [3H]MBZ. Using the displacement data. BZs were ranked according to their Ka and IC50 (concentration of BZ inhibiting 50% of radioligand binding) values. The Ka and IC50 values and the rank order of the BZs were approximately independent of the radioligand displaced or source (S or R) of the tubulin extracts used. The results are consistent with tubulin binding being the primary mechanism of action for all of these BZs. PMID- 2325708 TI - Filarial paramyosin: cDNA sequences from Dirofilaria immitis and Onchocerca volvulus. AB - The nucleotide sequence of a cDNA copy of the Dirofilaria immitis paramyosin gene was determined. The sequence was 2545 nucleotides in length, consisting of a single open reading frame of 848 amino acids capable of encoding a protein with a calculated molecular weight of 98,000. The cDNA clone was not complete, but probably includes over 97% of the coding region of the gene. We have previously observed that the cloned D. immitis paramyosin is recognized by sera from humans infected with Onchocerca volvulus. To determine the extent of homology at the protein level, we screened a cDNA library of O. volvulus with an antiserum made against D. immitis paramyosin. Ten recombinant clones were partially sequenced, comprising a total of 1186 nucleotides or 389 amino acids. The amino acid sequence of D. immitis paramyosin was 99% identical to the O. volvulus paramyosin. We also compared the amino acid sequence to other cloned paramyosins, and noted that 92% of the amino acids were identical to those of Caenorhabditis elegans, and 34% identical to those of Schistosoma mansoni. Comparison of the paramyosin sequence between different species revealed a hierarchy of similarities: (1) a 7-amino-acid repeat with apolar residues in the a and d position as the most conserved, followed by (2) the amino acid sequence and (3) the DNA sequence. PMID- 2325709 TI - The 5S ribosomal RNA genes of Crithidia fasciculata. PMID- 2325710 TI - Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. AB - Adrenocortical carcinoma is a rare tumor, and only limited information is available about its natural history and the effects of therapy. We studied 105 patients (75 female and 30 male; mean age, 46 years) with adrenocortical carcinoma who were referred to us between 1963 and 1987. The average duration of symptoms before diagnosis was 8.7 months. At the time of diagnosis, 68 percent of the patients had endocrine symptoms, and 30 percent had distant metastases. Hormonal studies showed that 79 percent of the tumors were functional. Eighty patients underwent surgery, and 59 also received the adrenal cytotoxic agent mitotane. The median disease-free interval after surgery was 12.1 months (range, 1 to 175). Tumor dissemination occurred in 82 percent of the patients, most commonly to the lung, liver, and adjacent organs. The median survival time was 14.5 months (range, less than 1 to 175), and the five-year survival was 22 percent. Age over 40 years and the presence of metastases at the time of diagnosis were the only factors recognized as indicating a poor prognosis. Mitotane controlled hormonal secretion in 75 percent of the patients. Eight mitotane-treated patients had partial tumor regression, but the drug did not have a significant effect on survival. We conclude that adrenocortical carcinoma carries a poor prognosis. Mitotane therapy may offer transient benefits, particularly in controlling endocrine symptoms. PMID- 2325711 TI - The prevalence of illicit-drug or alcohol use during pregnancy and discrepancies in mandatory reporting in Pinellas County, Florida. AB - Florida is one of several states that have sought to protect newborns by requiring that mothers known to have used alcohol or illicit drugs during pregnancy be reported to health authorities. To estimate the prevalence of substance abuse by pregnant women, we collected urine samples from all pregnant women who enrolled for prenatal care at any of the five public health clinics in Pinellas County, Florida (n = 380), or at any of 12 private obstetrical offices in the county (n = 335); each center was studied for a one-month period during the first half of 1989. Toxicologic screening for alcohol, opiates, cocaine and its metabolites, and cannabinoids was performed blindly with the use of an enzyme multiplied immunoassay technique; all positive results were confirmed. Among the 715 pregnant women we screened, the overall prevalence of a positive result on the toxicologic tests of urine was 14.8 percent; there was little difference in prevalence between the women seen at the public clinics (16.3 percent) and those seen at the private offices (13.1 percent). The frequency of a positive result was also similar among white women (15.4 percent) and black women (14.1 percent). Black women more frequently had evidence of cocaine use (7.5 percent vs. 1.8 percent for white women), whereas white women more frequently had evidence of the use of cannabinoids (14.4 percent vs. 6.0 percent for black women). During the six-month period in which we collected the urine samples, 133 women in Pinellas County were reported to health authorities after delivery for substance abuse during pregnancy. Despite the similar rates of substance abuse among black and white women in our study, black women were reported at approximately 10 times the rate for white women (P less than 0.0001), and poor women were more likely than others to be reported. We conclude that the use of illicit drugs is common among pregnant women regardless of race and socio-economic status. If legally mandated reporting is to be free of racial or economic bias, it must be based on objective medical criteria. PMID- 2325712 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 17-1990. A 16-year-old boy with painful swelling of the left knee joint and calf. PMID- 2325713 TI - Immunosuppression in organ transplantation. PMID- 2325714 TI - Prisoners of technology--the case of Nancy Cruzan. PMID- 2325715 TI - AIDS in subjects with hemophilia. PMID- 2325716 TI - Should we try malariotherapy for Lyme disease? PMID- 2325718 TI - Treatment of asthma. PMID- 2325717 TI - Cocaine-induced coronary-artery constriction. PMID- 2325720 TI - Universal health insurance: equivocation throughout nation. PMID- 2325719 TI - Pleural effusion due to unsuspected aspiration of vegetable matter in a three year-old boy. PMID- 2325721 TI - Exposure to bright light and darkness to treat physiologic maladaptation to night work. AB - Working at night results in a misalignment between the sleep-wake cycle and the output of the hypothalamic pacemaker that regulates the circadian rhythms of certain physiologic and behavioral variables. We evaluated whether such physiologic maladaptation to nighttime work could be prevented effectively by a treatment regimen of exposure to bright light during the night and darkness during the day. We assessed the functioning of the circadian pacemaker in five control and five treatment studies in order to assess the extent of adaptation in eight normal young men to a week of night work. In the control studies, on the sixth consecutive night of sedentary work in ordinary light (approximately 150 lux), the mean (+/- SEM) nadir of the endogenous temperature cycle continued to occur during the night (at 3:31 +/- 0:56 hours), indicating a lack of circadian adaptation to the nighttime work schedule. In contrast, the subjects in the treatment studies were exposed to bright light (7000 to 12,000 lux) at night and to nearly complete darkness during the day, and the temperature nadir shifted after four days of treatment to a significantly later, midafternoon hour (14:53 +/- 0:32; P less than 0.0001), indicating a successful circadian adaptation to daytime sleep and nighttime work. There were concomitant shifts in the 24-hour patterns of plasma cortisol concentration, urinary excretion rate, subjective assessment of alertness, and cognitive performance in the treatment studies. These shifts resulted in a significant improvement in both alertness and cognitive performance in the treatment group during the night-shift hours. We conclude that maladaptation of the human circadian system to night work, with its associated decline in alertness, performance, and quality of daytime sleep, can be treated effectively with scheduled exposure to bright light at night and darkness during the day. PMID- 2325722 TI - Pseudohyperkalemia caused by fist clenching during phlebotomy. PMID- 2325723 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 18-1990. A 58-year-old man with hematochezia and a lesion of the cecum. PMID- 2325725 TI - Women in medicine. PMID- 2325724 TI - Strategies for resetting the human circadian clock. PMID- 2325726 TI - Outcomes of extremely-low-birth-weight infants. PMID- 2325727 TI - Suicidal ideation and suicide attempts in panic disorder. PMID- 2325728 TI - Intestinal electrolyte transport and diarrheal disease. PMID- 2325729 TI - Oncogenes, growth factors, and signal transduction. PMID- 2325730 TI - Transverse myelitis and spastic paraparesis in a patient with HIV infection. PMID- 2325731 TI - High priests of medicine. PMID- 2325732 TI - Laser-printer rhinitis. PMID- 2325733 TI - Enhanced local production of complement components in the small intestines of patients with Crohn's disease. AB - There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured jejunal-fluid concentrations of the complement components C4, C3, and factor B by perfusion of a closed segment of the jejunum in 22 patients with Crohn's disease thought to be limited to the terminal ileum. The mean (+/- SEM) jejunal-fluid C4 concentration was 2.0 +/- 0.3 mg per liter, significantly higher than the mean level in 35 healthy controls (0.7 +/- 0.1 mg per liter; P less than 0.001). The mean C3 concentration was 1.0 +/- 0.1 mg per liter in the patients and 0.7 +/- 0.1 mg per liter in the controls (P less than 0.05). The factor B levels were similar in the two groups. Calculated rates of intestinal secretion of these components showed differences of the same magnitude. Leakage of protein from plasma was not increased. The jejunal-fluid:serum ratios of these complement proteins indicated that their appearance in the lumen of the jejunum was due to at least in part to local mucosal synthesis. The increased jejunal secretion of C4, but not C3 or factor B, paralleled the clinical activity of Crohn's disease. Values were normal in first degree relatives of the patients (n = 13), patients with celiac disease (n = 8), and patients with ulcerative colitis (n = 4). We conclude that increased secretion of complement by clinically unaffected jejunal tissue in patients with Crohn's disease reflects the systemic nature of this disorder and may be due to the stimulated synthesis of complement by activated intestinal monocytes and macrophages. PMID- 2325734 TI - Hypoglycemia during diarrhea in childhood. Prevalence, pathophysiology, and outcome. AB - To determine the frequency and outcome of hypoglycemia during diarrhea in childhood, we screened 2003 consecutive patients less than 15 years of age who were admitted to a diarrhea treatment center in Dhaka, Bangladesh. Hypoglycemia, defined as a blood glucose concentration less than 2.2 mmol per liter, was found in 91 patients (4.5 percent), 39 (42.9 percent) of whom died. We also measured the plasma concentrations of glucoregulatory hormones and gluconeogenetic substrates in 46 of the patients with hypoglycemia who were 2 to 15 years old and in 25 normoglycemic patients matched with them for age and weight. The patients with hypoglycemia had had diarrhea for less time than the normoglycemic patients (median, 12 vs. 72 hours; P less than 0.05), and their last feeding had been 18 hours before admission, as compared with 9 hours for the normoglycemic patients (P less than 0.05). The groups were similar in terms of nutritional status, the proportion of patients who had fever, and the types of pathogens recovered from stool samples. The plasma C-peptide concentrations were low (less than 0.30 nmol per liter) in all the hypoglycemic patients. As compared with the normoglycemic patients, the patients with hypoglycemia had elevated median plasma concentrations of glucagon (44 vs. 11 pmol per liter; P = 0.001), epinephrine (3400 vs. 1500 pmol per liter; P = 0.012), norepinephrine (7500 vs. 2900 pmol per liter; P = 0.002), and lactate (3.5 vs. 2.1 mmol per liter; P = 0.020) and similar alanine and beta-hydroxybutyrate concentrations. Eighteen hypoglycemic patients with severe malnutrition had been ill longer than 26 better-nourished patients with hypoglycemia (median duration of illness, 18 vs. 10 hours; P = 0.023) and had lower median plasma concentrations of lactate (1.9 vs. 3.9 mmol per liter; P = 0.021) and alanine (173 vs. 293 micromol per liter; P = 0.040). We conclude that hypoglycemia is a major cause of death in association with diarrhea. Because the glucose counterregulatory hormones were appropriately elevated in the children with diarrhea and hypoglycemia, whereas the gluconeogenetic substrates were inappropriately low, we further conclude that the hypoglycemia observed in such patients is most often due to the failure of gluconeogenesis. PMID- 2325735 TI - Failure of zidovudine prophylaxis after accidental exposure to HIV-1. PMID- 2325736 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 19-1990. A 12-year-old boy with a long travel history and a hepatic mass. PMID- 2325737 TI - Diarrhea, malnutrition, euglycemia, and fuel for thought. PMID- 2325738 TI - Physicians in training and HIV. PMID- 2325739 TI - Restoring trust between patient and doctor. PMID- 2325740 TI - Dexamethasone and acute mountain sickness. PMID- 2325741 TI - Syncope and electrophysiologic testing. PMID- 2325742 TI - Point mutations in retinoblastoma. PMID- 2325743 TI - Erectile failure in systemic sclerosis. PMID- 2325744 TI - Esophageal tear caused by a tortilla chip. PMID- 2325745 TI - Rhinosporidiosis in man: case reports. AB - Three cases of rhinosporidiosis with complications, hitherto not reported, are presented. Frog-faced deformity and seizures were observed in one case, excessive bleeding, loss of olfactory sensation and septal perforation were noticed in the second case, while the third one exhibited a disseminated type of the disease. Clinical findings of these cases are discussed. PMID- 2325746 TI - Antagonistic potential of Gliocladium virens and Trichoderma longibrachiatum to phytopathogenic fungi. AB - Three isolates of Gliocladium virens (G1, G2 and G3) and two of Trichoderma longibrachiatum (T1 and T2) were screened against isolates of three soilborne plant pathogens namely Rhizoctonia solani, Sclerotium rolfsii and Pythium aphanidermatum. G. virens exhibited stronger hyperparasitism and wider biological spectrum than T. longibrachiatum. Further, similarities as well as variation was observed in the ability of the various isolates to invade the test pathogens in dual culture. For the hyperparasites, acidic pH range (5.0 to 5.5) favoured both growth and spore germination. The hyperparasites made direct contact with the pathogens followed by varied modes of attack invariably leading to cell disruption. Antagonists, G1 and G3 revealed strong antibiosis while T2 showed moderate effect. All the isolates produced enhanced levels of lytic enzymes adaptively and there were marked differences among them. However, no correlation was observed between these attributes and the hyperparasitic potential of the various isolates in dual culture. The relevance and the role of enzymes and toxic metabolite(s) in the antagonism of G. virens and T. longibrachiatum to these pathogens are discussed. PMID- 2325747 TI - Chromoblastomycosis in Malaysia. AB - Nine cases of histologically diagnosed chromoblastomycosis are reported from Malaysia. All the patients were males and ranged in age from 56 to 65 years. The duration of symptoms varied from 5 months to 13 years. All the lesions were noted in the lower limbs. Malignancy was suspected clinically in 5 cases. The diagnosis was established by finding characteristic brown muriform cells in the tissue sections. PMID- 2325748 TI - Mycology studies in space. AB - The postflight phase of the Apollo MEED mycology attempts to identify survival according to exposure to specific quantitative space flight factors, while the second phase of studies identifies qualitative change other than cell survival [57]. Initial changes incurred in space on a fungal cell can be monitored and further examined on return of the fungal species test system to Earth. The postflight studies present a better understanding of the space environmental influences on living cells and a more clear understanding of the fungal species under examination. PMID- 2325749 TI - Investigation on lead and cadmium binding to gluten proteins of wheat flour. PMID- 2325750 TI - [Water binding of adsorptive immobilized lipases]. AB - It is supposed that not only the total water content of lipase preparations but more their state of water binding is of technological importance in enzymatic interesterification reactions in systems nearly free from water. The isotherms at 65 degrees C of two microbial lipases immobilized on various adsorbents as well as different adsorbents themselves are shown. The water binding capacity in the range of water content of technological interest decreases from the anion exchange resin Amberlyst A 21 via nonpolar adsorbent Amberlite XAD-2 to kieselguhr Celite 545. It is demonstrated that water binding by lipases is depending on temperature but is also affected by adsorptive immobilization. Adsorptive immobilized lipases show hysteresis, which is very important for preparing a definite water content of the enzyme preparations. PMID- 2325751 TI - Edible products from pelagic bissaria (Atherina mochon) fish. AB - The study was concerned with the utilization of small pelagic bissaria (Atherina mochon) fish in preparing edible, cheap, acceptable and nutritive products. The results confirmed the successful use of the mince of both the whole and beheaded gutted fish either alone or after mixing with different levels of plant sources (e.g. rice, wheat, potato, sesame butter, spices) in producing fresh fish ball, fish flour and spiced salted fish paste. Generally, the panelists preferred the products made from beheaded gutted fish mince above that prepared from whole one. The utilization of plant sources improved the technological properties of the products. The influence of processing on the chemical composition of these products was studied and tabulated. PMID- 2325752 TI - Role of zinc in regulating the testicular function. Part 3. Histopathological changes induced by dietary zinc deficiency in testes of male albino rats. AB - Zinc deficiency affects the testicular tissues adversely. The testes of zinc deficient rats showed variable degrees of degeneration compared to both control and zinc-supplemented ones. Initially, there was an early pronounced spermatic arrest followed by a series of degeneration of the cellular layers constituting the seminiferous tubules in the zinc-deficient rats. Degenerative changes were additionally demonstrated in the interstitial tissue cells of the zinc-deficient rats. These histopathological observations in testes of zinc-deficient rats run in parallel provide an additional support to our previous publications in which we recorded a significant reduction in both serum and testicular levels of testosterone in the same group of animals, since spermatogenesis in rodents appeared to depend primarily on testosterone level. PMID- 2325754 TI - [Comparative studies of the quantitative determination of tocopherols]. PMID- 2325753 TI - Direct sampling gas-liquid chromatographic--mass spectrometric analysis of hexanal from non-nitrite and nitrite-cured bacon during storage. AB - Direct sampling gas-liquid chromatography-mass spectrometry was used to quantitate hexanal levels in nitrite and non-nitrite cured loin bacon stored for two weeks at 4 degrees C. The objective was to evaluate the effect of varying levels of sodium nitrite on the flavour of cured bacon. Non-nitrite cured bacon yielded greater amounts of hexanal than bacon cured with 40, 120 and 1000 ppm sodium nitrite. Initially the differences were not significant but became evident during storage. Hexanal produced by samples during storage paralleled subjective undesirable flavour estimates (r = -0.88) and would undoubtedly be useful as an indicator of oxidative deterioration or rancidity for this product. PMID- 2325755 TI - A method for the quantitative determination of omega-3-polyunsaturated fatty acids by reductive ozonolysis. PMID- 2325756 TI - Estimation of the weekly intake of mercury which may be consumed by university students from the city of Havana. PMID- 2325757 TI - Determination of aflatoxins and ochratoxin A in animal tissues. PMID- 2325758 TI - Modified method of phytic acid analysis in rapeseed. PMID- 2325759 TI - Rehabilitation services for mining injuries. PMID- 2325760 TI - Management of babies with some less obvious congenital abnormalities. PMID- 2325761 TI - [Workshops: the workshop as a didactic form for the presentation of clinical practice in public health nursing]. AB - The use of the workshop as a didactical method in the presentation of clinical practica to community health nursing students at the distance teaching University of South Africa is described. The large number of students enrolled for this course at UNISA presented logistical problems to the services which offered opportunities for clinical practica to students. An outline of the course, as well as the objectives for the workshop, the contents, techniques applied and the evaluation is given. PMID- 2325762 TI - Hypoglycaemic presentation in a case of paediatric depression. PMID- 2325763 TI - Breastfeeding your premature baby. PMID- 2325764 TI - Father of numerous vaccines claims drugs best for AIDS. PMID- 2325765 TI - Implementation of public health research in the south-western Cape. PMID- 2325766 TI - Call for further study of alleged leukaemia link. PMID- 2325767 TI - Nuclear waste. Warning away future generations. PMID- 2325768 TI - Human Frontiers Program. Grant winners announced. PMID- 2325769 TI - US medical research healthy. PMID- 2325770 TI - Seeing the cellular translators at work. PMID- 2325771 TI - Human evolution. The Y of human relationships. PMID- 2325772 TI - Chloroplast DNA sequence from a miocene Magnolia species. AB - DNA has been successfully extracted from several samples of preserved tissue, the oldest so far reported originating from a 13,000-year-old ground sloth. Both severe damage to the preserved DNA, primarily due to oxidation of the pyrimidines, has prevented the acquisition of sequence data from ancient samples except in a few cases. We report here the extraction of DNA from fossil leaf samples from the Miocene Clarkia deposit (17-20 Myr old), the amplification of an 820-base pair (bp) DNA fragment from the chloroplast gene rbcL from a fossil of the genus Magnolia, and its subsequent sequencing. The sequence was verified by comparison with published and unpublished rbcL sequences. These results extend our ability to analyse ancient DNA and may open new avenues into problems in palaeobotany, biogeography, and in the calibration of mutation rates. PMID- 2325773 TI - Population structure of the human pseudoautosomal boundary. AB - The mammalian sex chromosomes are composed of two genetically distinct segments: the pseudoautosomal region, where recombination occurs between the X and Y chromosomes, and the sex chromosome-specific parts. Between these two segments the human sex chromosomes differ by the insertion of an Alu element on the Y chromosome. We have surveyed the sequence variation in the boundary region using the polymerase chain reaction. Fifty seven Y and sixty X chromosomes from ten different human populations were analysed. The X chromosomes were found to be polymorphic at five positions in a 300-base-pair region. By contrast, all Y chromosomes were identical except for one distal polymorphism shared with the X chromosome. PMID- 2325774 TI - Compartmentalization of cold-stable and acetylated microtubules in the subsynaptic domain of chick skeletal muscle fibre. AB - The junction between motor nerve and skeletal muscle in vertebrates is characterized by a complex subneural structure in which the nicotinic acetylcholine receptor (AChR) accumulates at a surface density of up to 10,000 20,000 molecules per microns 2. Among the mechanisms involved in the maintenance of the accumulation of AChR molecules is the localized expression of AChR subunit genes in the sarcoplasmic nuclei underlying the motor endplate, referred to as 'fundamental' by Ranvier. Immunocytochemical analysis has revealed that in innervated muscle fibres, the Golgi apparatus is also localized to subjunctional domains. We now report an accumulation of cold-stable and acetylated microtubules in the region of the sarcoplasm underlying the endplate. Together, these observations indicate that the subsynaptic sarcoplasm represents a compartment that is specialized both for the transcription, post-translational processing and stabilization of proteins of the postsynaptic membrane, in particular AChR, and for their targeting to the motor endplate. PMID- 2325775 TI - [Blunt and penetrating injuries of the heart]. PMID- 2325776 TI - [Indications for antibiotic prophylaxis in tonsillectomy]. PMID- 2325777 TI - [Prevention of wound infection following abdominal surgery]. AB - In the surgical department described, prevention of wound infection after abdominal operations involving endogenous bacterial contamination consists of a single preoperative administration of antibiotics according to a simple scheme, suitable for nursing staff also (using a combination of amoxicillin, tobramycin or metronidazole) with liberal application of open wound treatment. During the period from 1 July 1985 to 1 July 1986, 519 abdominal operations were performed, classified by increasing degree of contamination according to the classification of the American National Research Council (NRC) as NRC classes II to IV. In 371 cases, the wound was closed (NRC class II: 285; NRC class III: 86). In 148 cases (40%) the wound was intentionally left open (NRC class III: 51; NRC class IV: 97). In the group with NRC class II only two wound infections were seen. Inter alia there were no infections after 141 gall bladder/biliary tract operations, none after 46 gastrectomies and only one after 54 elective colon resections. In the group with NRC class III with 86 closed wounds, no wound infections occurred. All 148 wounds left open (NRC classes III and IV) healed smoothly, without significant morbidity, prolonged hospital stay or increase of the number of out patient follow-up visits; moreover, the cosmetic results were good. With specific antimicrobial prophylaxis in a single administration combined with liberal open wound treatment, postoperative wound infection after laparotomy appears to be virtually controlled. PMID- 2325778 TI - [Mirizzi syndrome]. AB - Obstruction of the common hepatic duct due to pressure from an impacted stone in the cystic duct or in the gallbladder infundibulum is known as Mirizzi's syndrome. The obstruction is due to direct impression of the stone on the common hepatic duct or to the concomitant inflammatory infiltrate. The diagnostic features are illustrated by 6 recently observed cases. Clinical features, sonography and CT scan do not always contribute to a correct diagnosis. Endoscopic retrograde cholangiography usually provides the diagnosis but confusion with gallbladder carcinoma, metastatic malignancies at the porta hepatis and even cholangiocarcinoma is possible. The therapy of the Mirizzi syndrome is essentially surgical. In obstructive jaundice preoperative direct cholangiography is always warranted even with a history suggestive of cholelithiasis. Especially in case of associated cholangitis non-surgical biliary drainage procedures are a valuable temporary treatment facilitating surgery. If, however, in a probably malignant obstruction of the common hepatic duct biliary stenting is considered as the only treatment, careful exclusion of Mirizzi's syndrome is required. PMID- 2325779 TI - [Eurothemes. Aging in a foreign country, an underestimated problem]. PMID- 2325780 TI - [Splenectomy as therapy for esophageal varices in a myeloproliferative syndrome]. PMID- 2325781 TI - [Treatment of non-insulin-dependent diabetes mellitus: a plea for comprehensive care]. PMID- 2325782 TI - Nursing Practice. Therapeutic touch--a healing meditation. AB - Recent years have seen a growing interest in and use of complementary therapies by nurses. This paper explores one technique, therapeutic touch, and its relevance to nursing practice. PMID- 2325783 TI - Independence and status--two different work methods. AB - This paper describes a study to establish whether there were hidden benefits from the changes occurring in nursing work methods. Of particular interest were the feelings of independence and status of qualified nursing staff operating within two discrete work environments, namely a) primary nursing, b) task allocation nursing. A nine item questionnaire with Likert scale was used as the measure. It was hypothesised that those nurses working with primary nursing would 1) feel more independence and, 2) have a higher sense of status than their counterparts in the traditional task-centred environment. PMID- 2325784 TI - Nursing practice. Developing a philosophy. AB - Christopher Johns, in Part 2 of this article, illustrates the process of defining a nursing philosophy. A case study is used to illustrate how clinical nurses can set about defining a philosophy of nursing for themselves. PMID- 2325785 TI - Continuing education for assistants. AB - This paper explores methods of applying staff development principles to untrained members of the nursing team, specifically care assistants or nursing auxiliaries. PMID- 2325786 TI - Developing standards for instructions to patients with glaucoma. AB - This paper describes the development of nursing standards in the management of patients with glaucoma. A key aspect was the development of understanding by patients of their problems. A survey was conducted to assess the respondents knowledge about glaucoma after application of the standard. The results achieved by the survey are explored. PMID- 2325787 TI - Homophobia, stigma and AIDS--an issue for all health care workers. AB - The AIDS epidemic has brought with it some fairly terrifying images of chronic illness and death among the young. Along with those images are the tremendous feelings of impotence (if that is the right word to use when writing about AIDS) which such an unknown infection creates among health care workers, who are used to dealing with somewhat more manageable entities. Yet, in their everyday work, nurses have to deal with many illnesses which are not particularly easier to cope with than those affecting the AIDS patient. The big difference is that AIDS related illnesses are less familiar and much more bound up in the moral and political framework of our society. PMID- 2325788 TI - Nursing practice. To visit--or not to visit. AB - In many settings, restrictions remain on visiting times in hospitals and in particular in coronary care units. This paper questions the appropriateness of restricted visiting times, examines relevant literature on the subject, and describes a small-scale project conducted in the author's own unit. The results of the study suggested that visiting times needed to be reviewed if the well being of patients was to be enhanced. PMID- 2325789 TI - [Suicidal symptoms in long-term follow-up of schizoaffective psychoses. Symptom constellations and social factors]. PMID- 2325790 TI - [Age-related psychopathologic peculiarities in endogenous and neurotic-reactive depression in advanced age]. PMID- 2325791 TI - [Percentile distribution of depression scales of the AMDP system]. AB - The severity of the depressive and apathy syndrome, which are factoranalytically derived from the AMDP-system is reported for 428 patients with a monopolar depression. The data are compared with the results from 79 patients with a bipolar depression, 192 with a neurotic depression and 89 with a depressive reaction. The percentile scores can be used for the evaluation of the severity of a depressive and apathy syndrome in comparison to a reference sample. PMID- 2325792 TI - [Therapeutic interventions in solvent abuse]. PMID- 2325793 TI - [Comments on the contribution by H. Hafner: Is schizophrenia a disease?]. PMID- 2325794 TI - Prevalence of chronic renal insufficiency in the course of idiopathic recurrent calcium stone disease: risk factors and patterns of progression. AB - The occurrence of chronic renal insufficiency was investigated in 171 patients with severe idiopathic calcium stone disease. Ninety healthy subjects matched for age and sex were used as controls. The patients were thereafter subclassified into two subgroups, assuming a GFR of 80 ml/min/1.73 m2 body surface area as a cut-off value: the normal GFR, 141 patients, and the impaired GFR, 30 patients. The normal GFR group included more males and the patients were younger both at onset and at presentation. In the impaired GFR group the disease lasted longer, but the overall stones and the stone recurrence rate were as high as those of the normal GFR patients. The single stone episodes were more severe in the former group as suggested by the occurrence of more surgery and complications. The GFR level was in part predicted by the age of patients; however, stone disease was shown to induce a clear-cut influence in accelerating the natural worsening of GFR with age. The onset of renal insufficiency causes multiple changes in renal pathophysiology, which result in a sharp decrease in the urine saturation with respect to calcium salts. These changes account for the decrease in the stone recurrence rate in the impaired GFR group. Thus, unless factors independent of or complicating the calcium stone disease supervene, the renal insufficiency of treated patients remains mild and relently progressive. PMID- 2325795 TI - Serum guanidino compound levels and clearances in uremic patients treated with continuous ambulatory peritoneal dialysis. AB - Guanidino compounds are increased in uremia and have been implicated as uremic toxins. The serum concentrations of 13 guanidino compounds and the clearances of 10 guanidino compounds were determined in 15 steady-state uremic patients treated with continuous ambulatory peritoneal dialysis. Guanidino compounds were determined using liquid cation-exchange chromatography with a sensitive fluorescence detection method. Standardized dialysis procedures were performed, including an overnight and a 3-hour dwell period. Guanidino compound levels did not significantly differ at the end of an overnight or a 3-hour exchange, indicating a steady-state blood chemistry for these substances in chronic ambulatory peritoneal dialysis. High levels were found for guanidinosuccinic acid, creatinine, guanidine and methylguanidine, while creatine and homoarginine levels were lower than in controls. Guanidinosuccinic acid, creatinine and methylguanidine reached levels associated with toxic effects in vitro. Significantly different clearances were found ranging from 4.02 +/- 1.08 ml/min for arginine to 7.94 +/- 2.76 ml/min for creatine during a 3-hour exchange. PMID- 2325796 TI - Macula densa cells of mouse kidney do not synthesize epidermal growth factor precursor mRNA. AB - Epidermal growth factor (EGF) has previously been found in cells of the thick ascending limb of Henle's loop (TALH) and the first part of the distal convoluted tubule (DCT) of mouse kidney. To define the cellular localization of the mRNA that encodes the protein precursor of EGF, we used high-resolution in situ hybridization. EGF precursor cDNA was hybridized to both paraffin-embedded and frozen sections of mouse kidney. EGF precursor mRNA was detected in cells comprising the TALH and the first part of the DCT. In contrast, tubular cells in the macula densa did not express this specific mRNA. The results indicate that expression of the EGF precursor gene is restricted to specific types of cells in the distal nephron. PMID- 2325797 TI - Changes in parathyroid hormone in diabetic patients on long-term hemodialysis. AB - Changes in parathyroid hormone (PTH) and osteocalcin over 3 years were studied in hemodialyzed patients with diabetic nephropathy (HD/DM) and hemodialyzed patients without diabetes (HD/non-DM). In HD/DM patients, concentrations of the carboxyl terminal regions of PTH and osteocalcin in the serum did not change significantly, but in HD/non-DM patients, both concentrations increased significantly. In patients in both groups, the mean concentration of the mid region of PTH increased significantly. Secondary hyperparathyroidism in HD/DM develops slower than in HD/non-DM. PMID- 2325798 TI - A low-protein diet protects uremic rats against the negative sequelae of metabolic acidosis. AB - Metabolic acidosis is a common finding in uremia. The metabolic consequences, however, are poorly understood. Thus, the aim of our study was to assess the effect of chronic metabolic acidosis in 5/6-nephrectomized male Sprague-Dawley rats given a normal (18%; n = 19) and a low-protein diet (8%; n = 23). Each of these groups was sequentially given CaCO3 and CaCl2 in the drinking water for a fortnight each. The animals were randomly assigned to start either with CaCO3 or CaCl2 (random cross-over design). The blood pH decreased significantly in both CaCl2 groups (18% protein: CaCO3 7.18 vs. CaCl2 7.11; 8% protein: CaCO3 7.26 vs. CaCl2 7.09) as did standardized base excess (18% protein: CaCO3-5.9 vs. CaCl2 9.7; 8% protein: CaCO3-3.6 vs. CaCl2-12.6). Food intake declined during acidosis in both groups, but more in the 18% protein group. The same occurred with body weight (g) in the 18% group, which decreased dramatically (8% protein: CaCO3 389 vs. CaCl2 390; 18% protein: CaCO3 413 vs. CaCl2 366). The change in body weight was reflected in the urinary urea excretion (mg/24 h/g food) (8% protein: CaCO3 0.9 vs. CaCl2 1.0; 18% protein: CaCO3 2.2 vs. CaCl2 30.8). There was a significant increase in proteinuria (mg/24 h) in the 8% group (CaCO3 10 vs. CaCl2 15), while in the 18% group no real change occurred (CaCO3 24 vs. CaCl2 18). Factoring the proteinuria for food intake, however, also resulted in a tendency towards an increased proteinuria in the 18% group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325799 TI - Genetic regulation of the development of glomerular sclerotic lesions in the BUF/Mna rat. AB - BUF/Mna strain rats spontaneously develop renal glomerular sclerotic lesions (RSL) at a nearly 100% incidence, diagnosed by hyperalbuminuria (greater than 500 mg/dl) and glomerular lesions morphologically resembling one type of human focal glomerular sclerosis (FGS). Genetic segregation of RSL development was studied by crossing the BUF/Mna strain with two other rat strains, WKY/NCrj and ACI/NMs, which were free of RSL. Two autosomal recessive genes in the BUF/Mna rats were found to determine the susceptibility to RSL in both combinations of crosses. PMID- 2325800 TI - Mesangial IgA deposits in two patients with AIDS-related complex. AB - Two patients with AIDS-related complex who presented with renal failure and microscopic hematuria were found to have mesangial deposits of IgA at renal biopsy. Though such glomerular deposits have not yet been reported in patients with HIV infection, their occurrence is most likely not coincidental. Indeed, there are striking similar abnormalities in patients with primary IgA nephropathy and in those infected with HIV. A careful screening for microscopic hematuria may lead to disclose further cases of mesangial IgA deposits in patients with HIV infection. PMID- 2325801 TI - Loss of renal graft due to recurrent IgA nephropathy with rapidly progressive course: an unusual clinical evolution. AB - Recurrence of IgA nephropathy following renal transplantation has been described in 40-50% of patients, and it usually has a good outcome. We present the case of a 54-year-old man with IgA nephropathy who developed terminal renal failure in 1985, 3 years after the onset of the disease. In March 1986 he received a cadaveric renal allograft following treatment with ciclosporin and steroids. Eight months later he developed microhaematuria and proteinuria and 10 months later he developed acute nephritic syndrome and rapidly progressive renal failure. Renal biopsy disclosed an IgA nephropathy with epithelial crescents in 60% of glomeruli. Treatment with plasma exchange and cyclophosphamide was unsuccessful and the patient lost his graft and returned to regular haemodialysis 15 months after renal transplantation. PMID- 2325802 TI - Acral gangrene attributed to calcific azotaemic arteriopathy and the steal effect of an arteriovenous fistula. AB - We describe a young male non-smoker who developed acral gangrene within 4 months of commencing haemodialysis. Amputation of the left hand proximal to the wrist was ultimately required. The onset of peripheral gangrene in this dialysis patient is attributed to calcific azotaemic arteriopathy and the steal effect of an arteriovenous fistula. PMID- 2325803 TI - Early start of intensive therapy in malignant form of IgA nephropathy. PMID- 2325804 TI - Association of IgA nephropathy and myasthenia gravis. PMID- 2325805 TI - Effects of cool dialysate in dialysis-related symptoms. PMID- 2325806 TI - Treatment of hyperlipidemia with probucol reduces proteinuria in puromycin aminonucleoside-induced nephrotic rats. PMID- 2325807 TI - Membranoproliferative glomerulonephritis presenting with hypokalemia. PMID- 2325808 TI - Renal function in the elderly. PMID- 2325809 TI - Red cell volume distribution curves in diagnosis of glomerular and non-glomerular haematuria. PMID- 2325810 TI - Detection of malondialdehyde levels and superoxide dismutase activities in renal tissues of nonobese diabetic mice. PMID- 2325811 TI - Membranoproliferative glomerulonephritis presenting as malignant hypertension. PMID- 2325812 TI - The need for multiple time points in aging studies. PMID- 2325813 TI - Symmetrical and asymmetrical changes in brain tissue with age as measured on CT scans. AB - Age-related changes in mean CT attenuation values of brain tissue were analyzed by an objective, automated technique. Study participants included 64 healthy men ranging in age from 31 to 87 years. Five CT slices from each individual were evaluated: the last ventricular slice and the next four supraventricular slices. Regression analyses indicated that specific regions in the brain change with age. A schematic reconstruction of these regions suggests that several brain regions are selectively altered with age. On the medial aspect of the cerebral hemisphere there was bilaterally symmetrical atrophy of the cingulate gyrus and sulcus, the adjacent interhemispheric frontal gyri, the parietooccipital sulcus, and the marginal branch of the cingulate sulcus. On the convexity of the cerebral hemispheres there was asymmetrical widening of the central and postcentral sulcus on the left, and the intraparietal sulcus on the right. PMID- 2325814 TI - Quantitative assessment of cortical synaptic density in Alzheimer's disease. AB - Significant progress has been made over the last decade in delineating the neuropathological and neurochemical changes in the brains of patients with Alzheimer's disease (AD). Less well studied are the actual synaptic connections of affected areas of the brain, such as the cerebral cortex. Because the final common pathway for neurotransmission involves synaptic integrity, we quantitatively assessed synaptic number and synapse size in lamina III and V of human frontal cortex (Brodmann area 9) in patients with AD and age-matched controls. Samples were also matched for postmortem interval, and artifacts associated with postmortem change were eliminated. We found a significant decrease in synaptic number per unit volume in both lamina, more marked in lamina III (-42%) than V (-29%). In both normal controls and AD brains, there was a negative correlation between synapse number and synapse size as indexed by the length of the postsynaptic density (PSD); cortical samples with fewer synapses had larger synapse size. This appeared to be a compensatory response, rather than a selective loss of small synapses, since the total amount of synaptic contact area per unit volume did not decline in lamina V (despite a 29% loss of synapses); in lamina III it was reduced 11% despite a 42% loss of synapses. The loss of synapses in AD is widespread and significant in frontal cortex; there is observable compensation by enlargement of synaptic size. This compensatory effort is overcome by the continuing loss of synapses in areas most affected by the degeneration. PMID- 2325815 TI - Effects of aging and vincamine derivatives on pericapillary microenvironment: stereological characterization of the cerebral capillary network. AB - Changes in the pericapillary microenvironment of adult (18-month-old) and senescent (27 1/2-month-old) Fischer-344 rats treated for 6 weeks with daily IP injections of brovincamine or apovincamine (0, 2.5, 5, 10 mg/kg) were correlated with spontaneous locomotor activity and [14C]-2-deoxyglucose uptake of the brain. The animals were tested for spontaneous locomotor activity in a tunnel maze. Twenty-four hr after behavioral testing and subsequently after a [14C]-2 deoxyglucose injection, brains were removed and capillaries stained with alkaline phosphatase reaction, being later measured with an optical-electronic image analysis technique. Results revealed an increase in intercapillary distance, as a sensitive parameter for capillary density, in the hippocampus (CA1) and in the parietal cortex (area 39) in association with aging. Capillary diameter in the parietal cortex was found to be increased age dependently. A similar age-related increase was also observed in the CA1 field but this age trend was not significant. Chronic treatment with the vincamines produced a dose-dependent reduction in intercapillary distance in senescent animals which approached the level of untreated adult control rats. Significant negative correlations were found between maze locomotion and intercapillary distance among senescent rats. Furthermore, intercapillary distance and local relative 2-deoxyglucose uptake tended to be negatively correlated in both age groups. These findings provide evidence for the working hypothesis that mean intercapillary distance can be considered as an indicator of neuronal activity in the pericapillary microenvironment. PMID- 2325816 TI - The noradrenergic innervation of spinal cord blood vessels in old rats. AB - The density and pattern of the sympathetic noradrenergic innervation of the extramedullary and intramedullary blood vessels of the spinal cord was studied in 3-, 12- and 25-month-old male Wistar rats using combined catecholamine histofluorescence and quantitative image analysis techniques. The study of innervation of intramedullary vessels was accomplished in spinal cord-transected rats to avoid the interference of descending spinal monoamine fibres in the observations. No age-related changes in the density of noradrenergic innervation of the anterior spinal artery or of sympathetic fibres associated with spinal cord blood vessels occurred. These results suggest that unlike perivascular noradrenergic nerves supplying the cerebrovascular tree, the sympathetic innervation of spinal cord blood vessels does not undergo age-dependent changes. It cannot be excluded that the lesser vulnerability of the spinal compared to the cerebral vascular tree to certain kinds of age-related diseases, may depend on the unchanged sympathetic trophic regulation of spinal vessels with age. PMID- 2325817 TI - Carnitine acetyltransferase activity is not changed with age in rat brain and human platelets. AB - Carnitine acetyltransferase activity was studied in different brain regions of the rat and in human platelets. The values of Km for carnitine and for acetyl CoenzymeA (acetyl-CoA) were similar in cortex, hippocampus and striatum of the rat and in human platelets, suggesting that carnitine acetyltransferase might be a useful peripheral marker of its central activity. The activity of this enzyme was similar in the cortex and hippocampus of young and old rats. Furthermore, the determination of carnitine acetyltransferase activity in platelets from healthy volunteers showed no significant difference with age. PMID- 2325818 TI - Should a unified nomenclature be adopted for the amyloid protein of Alzheimer's disease? PMID- 2325819 TI - The nomenclature of the cerebral amyloid fibril protein in Alzheimer's disease. PMID- 2325820 TI - The nomenclature of the cerebral amyloid fibril protein in Alzheimer's disease. PMID- 2325821 TI - The effect of selective noradrenergic denervation on thyrotropin secretion in the rat. AB - The effect of DSP4 [N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine], a neurotoxin which selectively lesions noradrenergic projections from the locus coeruleus, on thyrotropin (TSH) secretion was investigated in the rat. DSP4 treatment (60 mg/kg injected i.p. 10 days prior to experimentation) significantly decreased the noradrenaline (NA) content of the hippocampus, frontal cortex and hypothalamus of the rat brain. DSP4 treatment did not affect the clonidine (250 micrograms/kg, i.p ) or TSH-releasing-hormone (TRH 5 micrograms/kg i.v.) induced stimulation or the isoproterenol induced inhibition of TSH secretion in the rat. These results suggest that the noradrenergic projection from the locus coeruleus to the hypothalamus does not play a significant role in the regulation of TSH secretion. Furthermore, the noradrenergic deficiency did not give rise to the development of the abnormal TSH response to TRH administration which is frequently observed in depression. PMID- 2325822 TI - Histidine decarboxylase from rat and rabbit brain: partial purification and characterization. AB - Histidine decarboxylase, the synthetic enzyme for histamine, was partially purified from regions of rat or rabbit brain rich in the enzyme. The enzyme was purified using ion exchange and hydrophobic column chromatography and chromatofocusing. Approximately 70-fold and 110-fold enrichments were attained from rat and rabbit brain, respectively. Rat and rabbit brain histidine decarboxylase had isoelectric points of pH 5.4 and 5.6, Km values of 80 microM and 120 microM histidine and Vmax values of 210 and 625 pmol histamine formed/hr mg protein, respectively. The partially purified histidine decarboxylase from both sources was dependent on pyridoxal phosphate for maximal activity and was inhibited by alpha-fluoromethylhistidine, nickel chloride and cobaltous chloride but was not inhibited by impromidine, alpha-methyldopa, DTNB, zinc chloride or mercuric chloride. The enzyme had a broad pH optimum between pH 7.2 and 8.0. These studies provide further information on the characteristics of mammalian histidine decarboxylase from brain. PMID- 2325823 TI - Brain asymmetry in phospholipid polar head group metabolism: parallel in vivo and in vitro studies. AB - Phospholipid content and 32P-incorporation have been studied in individual rat cerebral hemispheres. The total phospholipid content was 44.9 +/- 0.9 and 47.9 +/ 1.3 mumol lipid P/100 mg protein for the right and left hemispheres respectively. Individually, only sphingomyelin was significantly (about 30%) higher in the left hemisphere. Metabolic experiments have been conducted in vivo using i.p. injection of 32P and following its incorporation into total and individual phospholipids in each cerebral hemisphere. Higher incorporations were attained by phosphatidate and phosphatidylinositol-4,5-bisphosphate (PIP2) in the left cerebral hemisphere than in the right. In an attempt to determine whether phospholipid metabolism is also lateralized in specific subcellular compartments related with the neurotransmission process, we have studied in vitro the [32P] incorporation into phosphoglycerides of synaptosomal fractions obtained from each cerebral cortex. The precursor was taken up differently by the two cerebral cortex preparations, resulting in different profiles of distribution among lipids. In addition, the kinetics of lipid labeling showed higher rates of 32P incorporation in fractions derived from the left cerebral cortex, mainly in PIP and PIP2. These results are interpreted to indicate that several enzymes involved in lipid metabolism are modulated to a different extent in the two hemispheres. PMID- 2325824 TI - Effects of atropine on the release of newly synthesized acetylcholine from rat striatal slices at various concentrations of calcium ions. AB - The release of acetylcholine (ACh) from brain tissue is known to be inhibited by muscarinic autoreceptors on cholinergic nerve terminals but the mechanism of the inhibition is not understood. Atropine brings about an increase of ACh release by removing the inhibitory action of autoreceptors. We investigated whether the effect of atropine on the release of [14C]ACh newly synthesized during incubations from [U-14C] glucose depends on the concentration of Ca2+ in the medium. In rat striatal slices incubated in the presence of an inhibitor of cholinesterases and of 30 mmol/l K+, significant increases in the release of [14C]ACh elicited by atropine were only observed during incubations with very low concentrations of Ca2+. This finding supports the view that the activation of presynaptic muscarinic autoreceptors in the brain affects the release of ACh by reducing the availability of Ca2+ that is required for transmitter liberation. PMID- 2325825 TI - Time course of induction of a heat shock gene (hsp70) in the rabbit cerebellum after LSD in vivo: involvement of drug-induced hyperthermia. AB - In situ hybridization studies were carried out to determine whether induction of hsp70 mRNA in various cellular layers of the rabbit cerebellum was due to hyperthermic effects of the psychotropic drug LSD. Results indicated that induction was not present when LSD-induced hyperthermia was blocked. The pattern of induction of hsp70 mRNA in various cell types of the cerebellum was similar when hyperthermia was induced by either drug (LSD) or nondrug means (placement of animals in a warm incubator). A time course analysis of the induction of hsp70 mRNA following LSD-induced hyperthermia revealed maximal levels of mRNA at 1 hr in all cerebellar cell layers except the Purkinje layer where highest levels were attained at 5 hr. By 10 hr hsp70 mRNA had returned to constitutive levels in all cellular layers of the cerebellum. PMID- 2325826 TI - Alcohol withdrawal-induced changes in brain biogenic amines in mice: influence of the genotype. AB - Alterations in striatal and hippocampal dopamine (DA) and serotonin (5HT) activities were investigated in two inbred strains of mice (C57B1 and Balb/c) after 3 withdrawal periods following 5 months chronic ethanol administration. Two groups of animals with different levels of ethanol administration (15% and 30%, v/v) were examined. A striking strain dependency has been noted. Striatal dopaminergic mechanisms of the Balb/c strain are profoundly disturbed in both groups. In contrast no changes were noted for either transmitter activities in C57B1 mice at any withdrawal time studied. Strain dependency has also been noted for hippocampal serotonin neurotransmission, since only Balb/c mice showed a progressive decrease in 5HT levels. These impairments observed in striatum and hippocampus could be involved in motor incoordinations and convulsions often associated with the withdrawal syndrome. The differences in withdrawal effects we noted between the two strains may be linked to the specific chemical neuroanatomy of the strains. Such specificities could be implied in the well known variability of withdrawal induced behavior in man. PMID- 2325827 TI - The release of adenosine at the electric organ of Torpedo. A study using a continuous chemiluminescent method. AB - Acetylcholine and ATP are costored and coreleased during synaptic activity at the electric organ of Torpedo. It has been suggested that released ATP is converted to adenosine at the synaptic cleft, and in turn this nucleoside would depress the evoked release of acetylcholine. In the present communication we have used a chemiluminescent reaction that let us to monitor continuously the presence of adenosine in this preparation. The chemiluminescent reaction is based on the conversion of adenosine into uric acid and H2O2 by adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase enzymes. The hydrogen peroxide has been detected by peroxidase-luminol mixture. The reaction has a sensitivity on the picomol range and discerned between Adenosine, AMP, ADP, and ATP. We have developed this technique in the hope of understanding whether adenosine is released during synaptic activity or it comes from the released ATP. We have studied the release or formation of adenosine in fragments of the electric organ and in isolated cholinergic nerve terminals obtained from it. In both conditions we have followed the effect of potassium stimulation upon the detection of adenosine. Potassium stimulation increased the extracellular adenosine either in slices or the synaptosomal fraction of Torpedo electric organ. The presence of alpha, beta-methylene ADP, an inhibitor of 5'-nucleotidase, inhibits the detection of adenosine, suggesting that extracellular adenosine is a consequence of ectocellular dephosphorylation of released ATP. PMID- 2325828 TI - Developmental and regional alteration of methionine enkephalin-like immunoreactivity in seizure-susceptible E1 mouse brain. AB - Methionine enkephalin-like immunoreactivity (ME-LI) in the brain of El mice (seizure-susceptible strain) was measured by radioimmunoassay (RIA) to elucidate the relation between seizures and the opioid system. The lyophilized supernatants of tissue extracts were subjected to ME RIA. The concentration of ME-LI in 25-day old El mice that had no seizures was significantly decreased in the hippocampus. At the age of 50 days when El mice displayed abortive seizures, the levels of ME LI in both El(+) and nonstimulated El(o) mice were also significantly reduced in the hippocampus and septal area. It was further shown that the ME-LI concentrations in both 150-day-old adult El(+) during interictal periods and El(o) mice were markedly decreased in the cerebral cortex, septal area, and striatum, as compared with the corresponding regions in ddY mice (seizure nonsusceptible strain; the mother strain of El). The decrease of ME-LI in the El mouse brain was generally compatible with our previous findings concerning the up regulation of opioid delta receptors in this species. These results suggest that the reduction of ME-LI in the El mouse brain is not due to convulsions, but could be associated with the pathogenesis of seizure diathesis and seizure manifestations in the El mouse. PMID- 2325829 TI - Depolarization of the neuronal membrane caused by cotransport of taurine and sodium. AB - C 1300 neuroblastoma cells were cultured and used to study the effect of sodium dependent taurine transport on the membrane potential. Measuring net accumulation of taurine and the depolarization caused by externally applied taurine, we found both processes become active at an external concentration of taurine of 1 mM or more. Net accumulation had Km of 13 mM and a Vmax of 126 nmol x mg of protein-1 x min-1. The taurine induced depolarization of the neuroblastoma cell was parallelled by a 25 per cent decrease in its membrane impedance. The transport of taurine, the depolarization caused by taurine and the effect of taurine on the membrane impedance, all, had a similar dependence on the external sodium concentration. Our results on the depolarizing cotransport between taurine and sodium at the neuronal membrane, may illustrate an additional mechanism for the control of the electrical activity of neuronal cells. PMID- 2325830 TI - Effects of the enkephalinase inhibitor SCH 34826 on the sleep-waking cycle and EEG activity in the rat. AB - The sedative effect of SCH 34826, an enkephalinase inhibitor, was evaluated by studying electroencephalographic (EEG) activity, behaviour and the sleep-waking cycle in the rat. The reference opioid, morphine, was used for comparison. After administration of morphine (10 mg/kg s.c.) the rats were motionless and stuporous at first and then hyperactive. An increase of slow wave sleep, at the expense of both wakefulness and REM sleep was recorded, with high-amplitude slow wave bursts appearing in the EEG tracings during the waking, albeit stuporous, phase. Relative spectral power in the 1-4 and 12-16 Hz bands was increased and there was a shift of the dominant frequency to a lower frequency. The specific opioid antagonist, naltrexone, readily reversed most of these effects. The drug SCH 34826 (10-100 mg/kg p.o.) had no effect on the parameters examined; large doses (300 and 1000 mg/kg p.o.) induced restlessness in some animals, resulting in increased waking. This effect was antagonized by naltrexone. The data indicate that SCH 34826, at doses far greater than those proposed for clinical use, is devoid of sedative liability and does not induce any of the behavioural or EEG effects typical of morphine. PMID- 2325831 TI - Effects of D-baclofen and L-baclofen on the trigeminal nucleus. AB - D-Baclofen reduced the response to L-baclofen in the feline trigeminal nucleus, the spinal cord of the rat and in patients with trigeminal neuralgia, but not in slices of hippocampus or neocortex. The iontophoretic application of 10-20 nA L baclofen depressed excitatory transmission in the trigeminal nucleus oralis, similar to the effect of 0.1-0.4 mg/kg L-baclofen, given intravenously. The concomitant iontophoresis of 10-20 nA D-baclofen reduced the effect of iontophoretically applied L-baclofen. However, larger doses of D-baclofen (30-60 nA) did not, while still larger doses (200-400 nA) by themselves depressed response of the neuron, similar to the action of small doses of L-baclofen. The iontophoresis of 30-40 nA L-baclofen had a stronger effect than that previously obtained with systemic administration and D-baclofen was not able to block it. These observations suggest that D-baclofen is a partial agonist at the GABAB receptor. Failure to observe a blocking effect of D-baclofen in slices of hippocampus or neocortex could be due to the larger doses used or to a difference in receptor types. The observations emphasise the need to test drugs at therapeutic concentrations in an appropriate model, in order to predict reliably their therapeutic actions. PMID- 2325832 TI - Anticonvulsant modification of cocaine-induced toxicity in the rat. AB - A number of anticonvulsant drugs were studied for their efficacy in preventing seizures and death from intoxication with cocaine. Rats were first pretreated with the test drug then subjected to large doses of intraperitoneally administered cocaine. In this model, control animals developed seizures in approximately 6 min, followed by death in approximately 10 min. Statistically significant protection against seizures and death was afforded by pretreatment with diazepam, phenobarbitol and the blocker of the uptake of gamma-aminobutyric acid (GABA), SKF 100330A. Only partial protection was afforded by the N-methyl-d aspartate (NMDA) antagonist MK 801, the benzodiazepine antagonist, flumazenil and the novel aminobenzamide, LY 201116. Valproic acid and phenytoin demonstrated limited efficacy against cocaine-induced seizures, without consistently reducing death. Carbamazepine and ethosuximide did not significantly reduce seizures or death. In this model of acute cocaine toxicity, the anticonvulsants diazepam, phenobarbital and the blocker of the uptake of GABA, SKF 100330A were the most effective in protecting rats from cocaine-induced seizures and death. These data offer insight into future approaches for the treatment of patients with the acute toxic effects of cocaine. PMID- 2325833 TI - Ambient temperature modulation of fenfluramine-induced thermogenesis in the rat. AB - The anti-obesity drug fenfluramine, promotes loss of weight by reducing food intake; however, there is controversy as to whether the drug can also elevate expenditure of energy. Resting consumption of oxygen (VO2) was measured in conscious rats to determine whether the injection of fenfluramine increased metabolic rate and whether prior fasting, or ambient temperature altered the response. Regardless of whether the rats were fed or had been fasted for 22 hr, in a thermoneutral environment (28 degrees C), the intraperitoneal injection of dl-fenfluramine (20 mg/kg) caused a raised oxygen consumption. This elevation was sustained to the end of the 60-min period of measurement after the injection, at which point the colonic temperature was found to be increased. This metabolic response to fenfluramine was largely attenuated when the drug was administered at 23 degrees C, and the colonic temperature of the rats was decreased by 60 min after the injection. At 4 degrees C, the injection of fenfluramine inhibited thermogenesis against cold, the oxygen consumption fell and the rats exhibited hypothermia. It was concluded that fenfluramine can increase the metabolic rate, but that this effect is not conditional on associated food intake, as has been reported. Rather, the ambient temperature governs whether stimulation or inhibition of thermogenesis will be evoked. These metabolic effects of fenfluramine explain, in part, its divergent effects on body temperature, reported previously. PMID- 2325834 TI - Attenuation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity by tobacco smoke. AB - Several epidemiological studies have indicated that there may be an inverse relationship between smoking and Parkinson's disease. The purpose of this study was to determine whether chronic exposure to cigarette smoke alters the parkinsonian-like neurochemical changes caused by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) in mice. Following 4 weeks of brief, intermittent exposure to smoke, mice were treated with MPTP, 10 mg/kg. Smoke exposure was found to reduce the decrease in striatal dopamine and metabolite levels caused by MPTP. Although smoke exposure inhibited cerebral MAO-B activity, tissues from smoke-treated mice were able to metabolize MPTP in a normal fashion. This suggests that inhibition of cerebral MAO may not be a major mechanism for the apparent protective effect of cigarette smoke. PMID- 2325835 TI - Neuromedin U-like immunoreactivity in rat intestine: regional distribution and immunohistochemical study. AB - Neuromedin U-25 and its C-terminal octapeptide, neuromedin U-8 are related peptides originally identified in porcine brain which elicit potent uterus stimulant activity. Radioimmunoassay using an antiserum raised against porcine neuromedin U-8, indicated that neuromedin U-like immunoreactivity in the rat was far more abundant in the small intestine than the brain. Neuromedin U in the rat is a single, a 23 amino acid peptide (2, 17). Rat neuromedin U has the same 7 residues on its C-terminus as porcine neuromedin U, and the antiserum against porcine neuromedin U-8 is 100% crossreactive with rat neuromedin U. Immunohistochemical analyses using this antiserum revealed that neuromedin U immunoreactive structures in rat intestine were confined to the enteric nervous system, implying that neuromedin U may be involved in neuronal regulation of gut function. PMID- 2325836 TI - Impaired verbal reasoning and constructional apraxia in subjects with right hemisphere damage. AB - In addition to causing visuospatial deficits, damage to the right cerebral hemisphere also impairs other cognitive abilities, including those requiring higher-order aspects of language. The present study used a standardized test battery to examine the relationship between visuospatial abilities and comprehension of narrative material in subjects having unilateral right hemisphere damage (RHD). In a series of 41 consecutively admitted RHD subjects, impairments in abstracting information from narrative passages were as prevalent and as severe in magnitude as constructional apraxia. Moreover, the extent of the visuospatial and linguistic impairments were highly correlated. Although age, educational levels, and degree of premorbid brain atrophy were all found to influence performance, analysis of a select subgroup of the population established that the covariation of visuospatial and verbal impairments is related to right hemisphere damage per se. Clinically, these findings may be of significance for understanding the pervasive cognitive impairments that are often evidenced by RHD patients. PMID- 2325837 TI - Retrograde amnesia following unilateral temporal lobectomy. AB - Remote memory performance was assessed in a carefully matched sample of temporal lobectomy subjects and normal controls. Left temporal lobectomy subjects exhibited a consistent pattern of remote memory disturbance. Right temporal lobectomy subjects performed at the same level as normal controls. The pattern of impairment observed in left temporal lobectomy subjects was characterized by deficits in recall of chronological information from the past decade and extended to deficits in recall in some aspects of factual knowledge. The disorder could not be attributed solely to language deficits and was at least as severe as accompanying deficits in recent memory. These findings suggest that the left medial temporal region may play a significant role in recall of remote information in addition to its role in recent memory functions. PMID- 2325838 TI - Identification and discrimination disorders in auditory perception: a report on two cases. AB - Auditory perception was investigated in two brain-damaged subjects. The first patient had a left temporoparietal ischaemic lesion. He presented a right-ear extinction in dichotic tasks, as well as difficulties in understanding and repeating verbal material and impaired identification of melodies. All discrimination tests were well performed. The second patient had a right capsulolenticular and frontal ischaemic lesion. He presented a left ear dichotic extinction and severe difficulties in discrimination of environmental sounds and melodies but no major difficulty in naming and identification. From these results, it is hypothesized that identification and discrimination involve distinct mechanisms within the processing of auditory stimuli, and that they may be selectively disrupted in brain-damaged subjects. PMID- 2325839 TI - Do children with a specific reading disability have a general serial-ordering deficit? AB - Two experiments are described in which reading disabled subjects and their normal controls were tested for their ability to abstract sequential regularities from a noisy background. Subjects were presented with an adaptation of the repeated digits task of Hebb (1961) and its spatial analogue the Corsi Blocks (Milner, B. Br. Med. Bull. 27, 272-277, 1971). Normal subjects had a digit span significantly better than their block span and also significantly better than that of the disabled readers. This suggested that normal subjects have better defined "storage filters" for digits or a specific advantage in the construction of 'transitory filters' for verbal material. There were no differences between groups on block span. On the repeated digit sequences normal readers abstracted a relatively stable "storage filter" in the first five recurrent trials whereas the disabled readers showed no discrimination until the last five recurrent trials. On the repeated blocks task the disabled group performed as well as normal readers. Taken together this date gives strong evidence for a specific deficit in verbal serial organization in disabled readers but does not support a general deficit in serial organization. PMID- 2325840 TI - Subclassification of non-pathological left-handers poses problems for theories of handedness. AB - The throwing performance of 104 right-handers, and 96 left-handers with inconsistent and consistent hand preferences, as classified by the procedure used by Ponton (Neuropsychologia 25, 305-311, 1987), was examined. Left-handers with inconsistent hand preference write with the left, tap faster with the left, and perform better with the left on the Purdue Pegboard task (Peters and Servos, 1989), but are stronger in the right hand and throw better with the right hand. In the other two groups, strength and skill activities are laterally congruent. This poses difficulties for theories of handedness. PMID- 2325841 TI - Visuospatial attention: effects of age, gender, and spatial reference. AB - Visual attention is remarkably stable when spatial cuing is used, but non-spatial cues lead to slowing among females and older subjects. Non-spatial cues are associated with poorer performance during the middle stages of the menstrual cycle. Motivation increased overall response speed but not attentional measures, whereas increasing age was associated with generalized slowing and directional asymmetries. Right-eye dominance was correlated with slow responses to downward targets. These data suggest that attentional performance is modified by age, gender, and endocrine status when spatial reference is not present. PMID- 2325842 TI - Academic discipline, handedness and immune disorders. AB - Much debate has surrounded the relative contribution of genetic inheritance and environment to human intelligence. In addition, fetal hormones may influence brain development and affect the qualitative nature of intellectual skills. Geschwind and Behan, Proc. Natn. Acad. Sci. 79, 5097-5100, 1982, have suggested that such hormones may also influence both the development of handedness and the development of the immune system. Members of the faculty of the University of Oxford participated in a survey investigating field of study; handedness and immune disorders. Even amongst right-handers, mathematical academics are significantly more susceptible to rare immune disorders and four times likely as verbal academics, to have suffered from a language related problem in childhood. In contrast to previous suggestions, the incidence of left-handedness is not found to be high amongst pure mathematicians but is significantly higher amongst scientists using mathematical applications. PMID- 2325843 TI - Topographic disorientation--a case report. AB - Topographical disorientation can be dissociated in two levels, agnosic and amnesic. A case of topographical disorientation due to a glioma of the splenium of corpus callosum illustrates the dissociation between the topographical memory impairment and the normal performances on the perceptual topographic tests. PMID- 2325844 TI - Lateralized interference in finger tapping: initial value differences do not affect the outcome. AB - Willis and Goodwin, Neuropsychologia 25, 719-724, 1987, have suggested that asymmetric interference observed in dual-task/time-sharing studies may be a statistical artifact of "initial-values" differences and not hemispheric lateralization. In the present study lateralized finger-tapping interference produced by concurrent anagram solution was observed even after the initial right hand advantage in baseline tapping performance was removed experimentally. PMID- 2325845 TI - Evidence for a cholinergic mechanism of "learned" changes in the responses of barrel field neurons of the awake and undrugged rat. AB - Due to its functional importance and its large and highly differentiated central projections, the vibrissal system of rodents is a prime object for the study of sensory plasticity, especially at the cortical level: the representation of vibrissae in the "barrel field", a part of the somatic cortex, is exceptionally precise and is susceptible to experience-induced changes. In a previous series of experiments, we found that a sensory-sensory conditioning procedure, pairing two vibrissal stimulations, produces significant changes in responses of single neurons of the barrel field in the chronic awake and undrugged rat: (1) the appearance of an excitatory response to a stimulus that was ineffective before pairing ("conditioned response"); (2) the modifications of pre-existing responses consisting of the suppression of afferent inhibition and the appearance of long latency excitatory components. We report here that the micro-iontophoretic application of atropine abolishes "conditioned responses" and restores afferent inhibition. Acetylcholine facilitates an enlargement of the receptive field and induces a sustained mode of discharge to stimuli. These data provide a new and direct support to the hypothesis that cholinergic mechanisms are involved in the sensory cortex plasticity. PMID- 2325846 TI - A histamine-containing neuronal system in human brain. AB - A well-organized network of varicose fibers was revealed throughout the frontal and temporal cortex of adult humans with specific antisera against histamine. The densest network of fibers was seen in lamina I, where varicose fibers were seen to run in parallel to the overlying pia mater. Electron microscopic immunohistochemistry revealed histamine-immunostaining in granules in a small number of nerve fibers and varicosities. Hypothalamic samples obtained from autopsy brains of adult humans revealed numerous histamine-immunoreactive nerve cell bodies in the posterior basal hypothalamus in and around the tuberomammillary nucleus. The results suggest that a histaminergic neuronal system reminiscent of that described in rodents is present in human brain. PMID- 2325847 TI - Excitatory amino acid projections to the periaqueductal gray in the rat: a retrograde transport study utilizing D[3H]aspartate and [3H]GABA. AB - The afferents to the periaqueductal gray utilizing excitatory amino acid transmitters have been described in rat brain by autoradiography following microinfusion and retrograde transport of D[3H]aspartate. Parallel experiments employing injections of [3H]GABA established that the retrograde labelling found with D[3H]aspartate was transmitter-selective. Following infusion of D[3H]aspartate, perikaryal labelling was found in nine subcortical areas, particularly infralimbic and cingulate cortices, with a predominance of ipsilateral labelled perikarya. Heaviest cortical labelling was localized in perirhinal cortex, in an extensive band of cells adjoining the rhinal sulcus. The hypothalamus contained the heaviest perikaryal labelling within brain: D[3H]aspartate labelled cells in 11 hypothalamic and mammillary nuclei. Intense bilateral labelling was obtained in ventromedial hypothalamus, although the number of perikarya was lower contralaterally. D[3H]Aspartate also produced heavy ipsilateral labelling of perikarya in posterior hypothalamus. Labelling patterns in cortex and hypothalamus were precise and topographic, and [3H]GABA never labelled cells in these regions. Other telencephalic and diencephalic areas containing prominent, retrogradely labelled cells were the lateral septum, amygdala, zona incerta and lateral habenula. The relative density of labelled cells in mesencephalic areas was much lower than that found in cortex and hypothalamus, although D[3H]aspartate labelled a moderate number of perikarya in the inferior colliculus and cuneiform nucleus. A smaller number of heavily labelled cells was found in the parabrachial nuclei, Kolliker-Fuse nucleus and laterodorsal tegmental nucleus. Only occasional labelled perikarya were observed in the myencephalon. Low densities of labelled cells were found after the injection of [3H]GABA into the periaqueductal gray, and the only regions in which a small number of perikarya were labelled by both [3H]GABA and D[3H]aspartate were the dorsal raphe and parabrachial nuclei. Overall, the retrograde transport of D[3H]aspartate revealed a complex topographic and convergent network of afferent pathways to the periaqueductal gray likely to utilize an excitatory amino acid transmitter. Our findings confirm the selectivity of this neurochemical mapping technique and provide evidence that hypothalamic, habenular, subthalamic and cuneiform afferents to the periaqueductal gray utilize an acidic amino acid as their transmitter. They also confirm that corticofugal afferents to periaqueductal gray utilize an excitatory amino acid. PMID- 2325848 TI - Inhibition of an identified snail postsynaptic neuron evoked by stimulation of a peptidergic interneuron initiating bursting pacemaker activity in another neuron. AB - Beating neuron V8, whose activity is abolished upon interneuronal stimulation, has been found and identified in the CNS of the snail, Helix pomatia. It was found earlier that stimulation of the same interneuron initiates bursting pacemaker activity in another neuron. Under voltage clamp conditions interneuronal stimulation evoked a slow outward current in the V8 neuron with a latency of about 2 s. Intracellular injection of tetraethylammonium or Cs+ ions into the interneuron greatly increased the slow outward current amplitude. External application of CdCl2 (1 mM), LaCl3 (5 mM) or replacement of Ca2+ by Mg2+ ions reversibly abolished transmission between the interneuron and the V8 neuron. The neuronal membrane conductance increased by about three times on the maximum of the slow outward current development. Computer fitting showed that a decay of the slow outward current can be approximated by the sum of two exponentially decaying components with time constants of about 1 s and 16 s. Extrapolated reversal potential for a fast (1 s) component of the current was about -70 mV. A slow (16 s) component asymptotically decreased upon hyperpolarization and it was observed at even more negative potential than Ek. Theophylline (1 mM) and 3 isobutyl-1-methylxanthine (0.1 mM) reversibly increased the slow outward current amplitude, whereas imidazole (5 mM) and tolbutamide (5 mM) caused its reversible decrease. It is concluded that inhibitory monosynaptic transmission exists between the interneuron and the beating V8 neuron. Interneuronal simulation evokes an increase in the membrane potassium conductance and probably a decrease in stationary potential-dependent sodium conductance of the postsynaptic V8 neuron. The cellular cyclase system seems to be involved in the postsynaptic response. PMID- 2325849 TI - Quantified distribution of the serotonin innervation in adult rat hippocampus. AB - To quantify the serotonin innervation in adult rat hippocampus, serotonin axon terminals (varicosities) were uptake-labeled for light microscope radioautography in whole hemisphere slices incubated with 1 microM [3H]serotonin. The labeled varicosities were visualized as small aggregates of silver grains and counted with the aid of an image analysis system across all layers in representative sectors of subiculum, Ammon's horn (CA1, CA3-a, CA3-b) and dentate gyrus (medial blade, crest and lateral blade). Counts were obtained in six rats at three equidistant horizontal levels from the ventral two-thirds of the hippocampus. After double correction for duration of radioautographic exposure and section thickness, and measurement of the mean diameter of labeled varicosities in electron microscope radioautographs, the results were expressed in number of varicosities per mm3 of tissue. The overall density of hippocampal serotonin innervation was thus evaluated at 2.7 x 10(6) varicosities per mm3, and appeared significantly higher in subiculum (3.6 x 10(6)) and Ammon's horn (3.1 x 10(6)) than in dentate gyrus (2.2 x 10(6)). Subiculum and dentate gyrus-crest (2.0 x 10(6)) had the highest and lowest regional densities. There was a marked heterogeneity also in terms of laminar distribution. For example, the stratum moleculare of subiculum and CA1, and the stratum oriens of CA3 (5.2 x 10(6)) varicosities in CA3-a), showed much higher values than the pyramidal cell layer (0.7, 1.1 and 0.7 x 10(6) in CA1, CA3-a and CA3-b, respectively). Similarly, the granular layer of dentate gyrus had a much lower density (1.1 x 10(6)) than did the molecular (2.8 x 10(6)) and the polymorph layer (2.4 x 10(6)). From these data, it was possible to evaluate the mean endogenous amine content per hippocampal serotonin varicosity (0.05-0.07 fg), and the average number of serotonin varicosities per hippocampal neuron in both CA3 (130) and dentate gyrus (20-35). In the context of current data on the distribution of serotonin receptors and diverse actions of serotonin at the cellular level in hippocampus, such quantified information provides new insights on some basic properties of serotonin in this part of the brain. PMID- 2325850 TI - Effect of omega conotoxin on reflex responses mediated by activation of capsaicin sensitive nerves of the rat urinary bladder and peptide release from the rat spinal cord. AB - The aim of this study was to assess whether omega conotoxin fraction GVIA, a potent blocker of N- and L-type voltage-sensitive calcium channels, might interfere with reflex responses (micturition, blood pressure rise in spinal rats) produced by activation of capsaicin-sensitive sensory nerves of the rat urinary bladder. The effect of conotoxin was also investigated on reflex micturition persisting after capsaicin pretreatment. Following topical application onto the bladder, conotoxin did not affect the volume threshold to elicit micturition although it reduced the amplitude of volume-evoked bladder contractions. Likewise, topical conotoxin did not prevent the reflex rise in blood pressure elicited by sudden bladder distension or topical application of capsaicin onto the bladder. In contrast, topical lidocaine strongly prevented both reflex responses. After intrathecal administration, conotoxin produced a dose-dependent inhibition of volume-evoked bladder contractions and the cardiovascular reflex produced by mechanical or chemical stimulation of bladder nerves. Intrathecal conotoxin inhibited micturition also in rats pretreated with capsaicin (50 mg/kg s.c., 4 days before). Depolarization by high potassium (80 mM) produced release of both substance P- and calcitonin gene-related peptide-like immunoreactivity from superfused slices of the dorsal half of rat spinal cord. Capsaicin (1 microM) produced a similar effect, and a previous exposure to capsaicin prevented the effect of potassium. Conotoxin (0.1 microM) significantly reduced (about 50%) the potassium-induced release of neuropeptides from the dorsal half of the rat spinal cord. These findings indicate that conotoxin-sensitive calcium channels in the rat spinal cord play a role in the neurotransmission along reflex pathways activated by stimulation of capsaicin-sensitive nerves in the urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325851 TI - Altered cellular distribution of iron in the central nervous system of myelin deficient rats. AB - Under normal conditions, iron is found predominantly in oligodendrocytes, the myelin producing cell, in the rat brain. A genetic mutant strain of rats known as myelin deficient rats is examined in the present study because their number of oligodendrocytes is decreased and those oligodendrocytes present are structurally abnormal. The levels of iron in the liver (major site of iron storage) and in the pons-cerebellum did not differ statistically between the myelin deficient rats and the littermate control rats, whereas only half of the iron normally found in the cerebrum-midbrain was present in the myelin deficient rat. Histologically, iron was found predominantly in oligodendrocytes in the littermate control rats, as expected. In the myelin deficient rat, iron staining was confirmed to astrocytes and microglia. The results of this study strongly suggest that iron uptake into the brain continues in the absence of normal oligodendrocytes and myelin. Furthermore, these data suggest that iron metabolism can be substantially altered, as indicated by the accumulation of iron in astrocytes and microglia, when normal or near normal levels of iron are quantitatively demonstrated. The response of astrocytes and microglia to sequester the iron (presumably through phagocytosis) in the absence of invasive damage represents, to our knowledge, a new functional observation for these cells. Based on these observations it is clear that iron histochemistry in combination with quantitative analysis is necessary to interpret data regarding iron physiology, at least in neurobiology, and iron accumulation by astrocytes and microglia may provide clues of altered iron metabolism despite normal iron levels. PMID- 2325852 TI - Calcium-dependent potentials with different sensitivities to calcium agonists and antagonists in guinea-pig hippocampal neurons. AB - Effects of organic Ca channel blockers, Ca channel activators and omega-conotoxin on guinea-pig hippocampal CA1 neurons in vitro preparations were studied with intracellular recording methods. Most of the Ca channel blockers, such as prenylamine, D 600, flunarizine, nifedipine, cinnarizine and nicardipine (0.2-4 microM), raised the threshold for Na-dependent spike generation and decreased the amplitude of the spike afterhyperpolarization. Verapamil (5 microM) and diltiazem (5 microM) did not significantly alter the threshold and amplitude of the Na spike. Action potentials elicited in the presence of either tetrodotoxin (0.5 microM) and tetraethylammonium (20 mM) or tetrodotoxin (0.5 microM) and Ba (1.25 mM) consisted of an initial spike component followed by a long depolarization. Both responses were abolished by addition of Co (2 mM) or Cd (0.25-0.5 mM), or by superfusion with a low Ca (0.25 mM)-high Mg(15 mM) medium, indicating that the potentials resulted from Ca entry. The Ca-dependent slow depolarization was preferentially blocked by most of the organic Ca channel blockers at approximately one-third the concentrations (0.1-2 microM) which were required to shorten the Ca spike. When the cell in a solution containing tetrodotoxin (0.5 microM), Co (2 mM) and 4-aminopyridine (2 mM) was hyperpolarized and then depolarized by passing current pulses across the membrane, a transient depolarizing hump occurred on the decay phase of the electrotonic potential. This transient depolarization was abolished by Co (2 mM), Ni (2 mM) or most of the organic Ca channel blockers (0.2-5 microM). Diltiazem (5 microM) did not significantly change these Ca-dependent potentials. The evoked excitatory postsynaptic potential was very resistant to the Ca channel blockers. Approximately 2-10 times higher concentrations (0.5-3 microM) were necessary to decrease the excitatory postsynaptic potential amplitude than to shorten the Ca spike. On the other hand, the minimal concentrations and order of potencies of the Ca channel blockers for depressing the evoked inhibitory postsynaptic potential and for elevating the threshold for Na spike generation were almost the same. Dihydropyridine Ca channel activators, such as Bay K 8644, CGP 28 392 and YC 170 at low concentrations (0.1-1 microM), decreased the Ca spike, the Ca dependent slow depolarization and the evoked synaptic potentials, while the substances augmented the Ca-dependent transient depolarization. On the other hand, omega-conotoxin (5 microM) reversibly depressed the Ca spike and slow depolarization to the same degree, without affecting the transient depolarization and the evoked excitatory or inhibitory postsynaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2325853 TI - High-affinity glutamine uptake of the rat hippocampus during postnatal development: a quantitative autoradiographic study. AB - Glutamine uptake into hippocampal slices of the rat was investigated autoradiographically. The characteristics of registered [14C]glutamine uptake such as the incubation with the radiolabelled amino acid at a concentration of 3.5 mumol/l, sodium dependency, the distribution pattern of radioactive material, and the postnatal development of uptake capacity are comparable with those of high-affinity uptake of glutamate. Densitometric evaluation of grain density over hippocampal layers exhibited a marked enhancement of uptake capacity in the neuropil areas during the first postnatal weeks. In the strata oriens and radiatum (CA1) radiolabelling increased from day 2 to 25 by about 390 and 410%, in the strata oriens and lacunosum-moleculare of CA3 by about 350 and 375%, respectively. In contrast, the rise in the accumulation rate in cell body layers was negligible. The temporal and topographical profiles of glutamine uptake in the hippocampal neuropil correlated with those of the activity of phosphate activated glutaminase and parameters of maturation of the glutamatergic transmission system which have fairly similar time characteristics, suggesting a mutually causative relationship of all these factors. PMID- 2325854 TI - Service management concepts in hospitals. PMID- 2325855 TI - Tobacco sponsorship and advertising. PMID- 2325856 TI - Nursing school applications and admissions. PMID- 2325857 TI - [The value of venous digital angiography in the postoperative follow-up of thromboendarterectomy and aorto-iliac-femoral prosthetic replacement]. AB - Personal experience of 21 patients controlled by venous digital angiography following thrombendarterectomy and aorto-iliac-femoral prosthetic substitution is reported. The technique can be usefully employed because it is not too invasive and gives excellent results, peripheral venous injection usually being sufficient to document vasal recanalisation and prosthetic morphology. Venous digital angiography is therefore the examination of choice in the follow-up of patients submitted to aortofemoral revascularisation operations, a field in which traditional angiography has been little utilised owing to the problems of arterial approach. PMID- 2325858 TI - [Sulprostone in the prevention and therapy of hemorrhage due to postpartal uterine atony]. AB - Sulprostone (Nalador-Schering) was used on 25 cases of bleeding caused by post partum atonia that did not respond to conventional uterotonic treatment. The good results obtained led to the use of the drug whenever it was necessary to prevent haemorrhage independent of the risk factors that might cause its onset. PMID- 2325859 TI - [An examination of the correlations between the general population and the users of the Biella Mental Health Service]. AB - This paper correlates certain general population variables with that of the users of the Biella Mental Health Service. Age, sex, civic status and schooling are considered. Analysis of the data points to certain risk zones. The significance of these correlations is considered. PMID- 2325860 TI - [The training of family members in treatment with suggestive and autogenic psychotherapies. The advantages and limits]. AB - The first part of the paper examines the reasons for involving the patient's family in suggestion and autogenous therapy, giving details of the advantages and limitations of this involvement and listing the pathologies in which it is employed. Finally, the use of autogenous techniques as an aid in the diagnosis of the patient's individual and relational situation as well as the prognosis for a cure is briefly described. PMID- 2325861 TI - [The involvement of family members in treatment with suggestive and autogenic psychotherapies. An analysis of a case]. AB - The first part of the present work reports the case of a young man given suggestion and autogenous therapy. The second part presents some remarks on the technique employed. In particular the advantages derived from recourse to a variety of suggestion techniques followed by the patient's use of autogenous training at home are examined. Finally the advantages to be derived from involving the patient's family in the induction therapy and the autogenous treatment are reported. PMID- 2325862 TI - [The pathology of self-destruction. Personal experience. Clinico-statistical aspects]. AB - Personal experience of 165 cases of attempted suicide observed at the resuscitation centre of the Biella Hospital in the period 1983-1987 is reported. The patients are examined from the point of view of their personal status, job, previous pathologies with particular regard to depressive anxiety syndromes. Particularly noteworthy is the high incidence of mortality among patients who had tried suicide previously. PMID- 2325863 TI - [Emergency home psychiatric care and the role of the general physician. Evaluations and hypotheses]. AB - Some aspects of the activity of the Mental Health Service of Biella are described, particularly those regarding home care. Then, on the basis of a description of a clinical case, the functions and role that it is considered can be fulfilled by the general physician in cooperation with the psychiatrist during emergency hope care when the patient is not already known to the psychiatric service are outlined. PMID- 2325864 TI - [The activity of psychiatric consultancy within a general hospital. The relationship and institutional implications]. AB - The consultancy activity performed by Biella Ward of the local general hospital in 1979-1987 is described. After presenting data regarding the quantity and nature of consultancy requests, the medico-hospital cultural background relating to mental suffering is analysed. The hospital often tends to address only the patient's bidimensional aspects, excluding his internal being. Because of a mutual, tacit contact between physician and patient, the moment of admission is seen as a "somatic repair service". The psychological crisis usually arises in the form of the breakdown of the contract when the possible uncertainty of diagnosis and the prolongation of clinical examination affects the personality. In the specific case of Biella Psychiatry, the forced closure of the Psychiatric Diagnosis and Care Service about six years ago helped push the Psychiatrist towards a "liaison" role. PMID- 2325865 TI - [An epidemiological study of psychiatric emergencies at the Biella Department of Emergencies and Admissions in the 5 years of 1983-1987]. AB - The psychiatric intervention procedure at the Emergency and Registration Department (ERD) of Biella Hospital is examined. After a short introduction in which some general data are provided regarding Health Unit no. 47 of Biella and Unit no. 48 of Cossato, the data collected by the ERD psychiatric register are analysed. Data on ERD arrival modalities are reviewed and the type of diagnosis attributed by the psychiatrist to patients examined at the ERD is examined. The various types of responses given by the psychiatrist after consultancy are then presented. The time bands in which the request for psychiatric intervention mainly fall are then noted. The paper closes with remarks on the effectiveness over time of psychiatric intervention at the ERD. PMID- 2325866 TI - [CT in the study of a dissecting aortic aneurysm at the moment of rupture and complicated by left hemothorax]. AB - The diagnostic capacity of computed tomography in a rupture of a thoracic aorta aneurysm complicated by hemothorax is examined. Both the case examined and reports in the literature show the greatest importance and utility of CT for correct emergency diagnosis, in high risk patients, when other systems cannot be used in the first instance. PMID- 2325867 TI - [Computerized tomography in a case of malignant mesothelioma with atypical clinical manifestations]. AB - A case of pleural mesothelioma spread by its contiguity with the left retrocavitary region causing pain in the homolateral half of the abdomen is described in a subject who had received a rib injury several months earlier. Instrumental examinations revealed pleural lesions with effusion and a left paravertebral mass. PMID- 2325868 TI - [Primary neoplasms of the gallbladder. Remarks on a case series]. AB - Data relating to a series of 22 patients suffering from primary gallbladder cancer are reported. In 8 cases the condition was benign, in 14 malignant. In 21 cases, concomitant presence of gallbladder calculosis was encountered. Survival in patients with gallbladder carcinoma was poor and significant in only 2 cases in which the tumour was observed at a non-advanced stage. PMID- 2325869 TI - [The rhabdomyolytic syndrome: a not uncommon occurrence]. AB - The paper examines one aspect of a medical pathology that is rather unusual and often wrongly diagnosed: rhabdomyolysis (RMC). The series examined suggests that the pathology is relatively common and arises in a wide variety of clinical conditions. In view of the fact that the consequences of rhabdomyolysis may be serious, emphasis is placed on the fact that correct diagnosis may be obtained by the careful consideration of simple clinical parameters such as subjective symptoms, urine colour, urine strip test and serum CPK assays. PMID- 2325870 TI - [A left atrial myxoma. The clinical aspects]. AB - The paper describes a case of left atrial myxoma, which was unidentified for many years after the onset of symptoms, with emphasis on the necessity for instrumental investigations (particularly M-mode and two-dimensional echocardiography) in order to obtain an accurate and prompt diagnosis of these affections when the patient's clinical history justifies the suspicion. PMID- 2325871 TI - [Changes in the plasma levels of T3-T4 and TSH during surgical stress and anesthesia with isoflurane]. AB - The authors describe the blood level changes of T3, T4 and TSH in 17 patients undergoing urological surgery and isoflurane anaesthesia. The data were statistically processed and showed that isoflurane, used as the only anesthetic agent in 1.5%-2% concentrations, is not sufficient to block hormonal changes of the hypothalamus-hypophysis-thyroid axis caused by surgical stress. PMID- 2325872 TI - [Relapsing polychondritis. Apropos a case]. AB - Relapsing polychondritis is a rare disease of undetermined cause. The most frequently seen symptom is redness and swelling of cartilaginous ear, followed by cartilage inflammation elsewhere in the body and inflammation of special sense organs. This report describes recurrent attacks of relapsing polychondritis in one patient, who responded to low doses of corticosteroid therapy. The great relevance of cutaneous vasculitis in our patient, lead us to suggest that PR may fall in to the spectrum of systemic vasculitis. PMID- 2325873 TI - [A renal tumor in a female HIV-positive patient. A case report]. AB - Patients with the acquired immunodeficiency syndrome (AIDS) are at increased risk of developing certain malignant tumours. The authors report a case of renal tumour in a HIV-positive patient. PMID- 2325874 TI - [Biarticular endoprostheses of the hip. 2 years of experience]. AB - After briefly illustrating indications and biomechanical concepts of biarticular endoprostheses of the hip in the treatment of medial fractures of the femoral neck, a personal series from December 1985 to March 1988 is presented. 55 of 82 operated patients were followed up on the basis of purely clinical criteria, particular attention being paid to general preoperative conditions, the recovery of function and the rate of postoperative mortality. In conclusion, it is recalled that prognosis in fractures of the femoral neck is severe for generally gerontological reasons and the usefulness of biarticular endoprosthesis in the prevention of cotyloid wear and tear is underlined. PMID- 2325875 TI - [Initial experience with the Ilizarov apparatus in orthopedic and traumatological pathology]. AB - Personal experience of 4 years with the use of Ilizarov's apparatus is reported. The apparatus has been utilised on a routine basis in the treatment of complex fractures, in pseudarthrosis and in hypometrias. On the whole, the results obtained were positive, confirming the value of the apparatus and its ductility in the treatment of complex lesions of the skeleton. PMID- 2325876 TI - [Clinico-statistical correlations in 586 cases of femoral neck fractures. An analysis of 212 cases of Ender's osteosynthesis]. AB - The advantages and complications of osteosynthesis using Ender nails are described on the basis of experience with 212 cases treated in 1985-1988. It is concluded that this currently represents the treatment of choice for selected fractures of the femoral neck. PMID- 2325877 TI - [Antalgic treatment of acute herpes zoster. A clinical contribution]. AB - The paper considers the difficulty of pain control in acute herpes zoster and the considerable incidence of NPH in patients given the conventional medical therapies. After a short account of physiopathology of herpetic pain, the treatment of acute cases with epidural or sympathetic blockages using anaesthetics and cortisone is proposed. Personal experience in a series of patients with either acute herpes zoster or NPH who were treated with this method is reported with details of peculiarities and results. PMID- 2325878 TI - Brain autoradiographic study in the golden hamster after intracarotid injection of [14C]melatonin. AB - The distribution of [14C]melatonin [( 14C]MT) after systemic injection was studied in the plasma and brain of golden hamsters. Thin-layer chromatographic analysis indicated that the radioactivity of the biological samples taken at two different times following the injection of label was exclusively associated with [14C]MT. Representative autoradiograms revealed a heterogeneous localization of [14C]MT in the grey matter. Two min after injection, the highest regional values were found in the hippocampus, caudate-putamen, medial thalamus and choroid plexuses. Lower radioactive concentrations were observed in the cingulate and frontoparietal cortex, anterior thalamus, inferior colliculus, dorsolateral geniculate nucleus, lateral and medial hypothalamus and amygdala. Fifteen min after injection, a significant level of radioactivity remained in the hippocampus, caudate-putamen, ventral thalamus and hypothalamus area. The heterogeneous distribution and the partial retention of [14C]MT in the brain are compatible with the existence of specific brain binding sites for this hormone. PMID- 2325879 TI - Bifurcation of P9 far-field potentials induced by changes in the shoulder position. AB - Somatosensory evoked potentials to stimulation of the left median nerve were recorded from normal adults with reference to the right knee in the usual shoulder position and in an elevated shoulder position. A single peak of the P9 potentials in the former position bifurcated into two peaks in the latter position without changing the onset latency. This waveform change can be accounted for by changes in the resistance of the volume conductor around the nerve trunk. PMID- 2325880 TI - Phaclofen antagonizes post-tetanic disinhibition in the rat dentate gyrus. AB - Tetanic mossy fiber stimulation transiently reduced recurrent inhibition in the rat dentate gyrus. The post-tetanic depression of inhibition was maximal 200 ms after the tetanus and typically lasted for about 2 s. Phaclofen, a selective gamma-aminobutyric acid-B (GABAB) receptor antagonist, significantly increased the post-tetanic level of inhibition. These results suggest that GABAB receptor activation is important for the development of post tetanic disinhibition. We suggest that GABA released during repetitive firing acts on GABAB receptors on inhibitory interneurons to suppress recurrent inhibition. PMID- 2325881 TI - Inhibition of protein kinase C prevents phorbol ester- but not muscarine-induced depolarizations in the rat superior cervical ganglion. AB - The role of protein kinase C (PKC) activation in mediating muscarinic depolarization was assessed in the rat superior cervical ganglion. Staurosporine, an inhibitor of PKC, abolished a depolarization elicited by the direct PKC activator beta-phorbol 12,13-dibutyrate, but had little effect on the response to muscarine. Thus, activation of PKC may not be an obligatory transduction step between muscarinic receptor stimulation and depolarization. PMID- 2325882 TI - Effects of pertussis toxin on the affinity of exocytosis for Ca2+ in bovine adrenal chromaffin cells. AB - Effects of pertussis toxin (islet-activating protein, IAP) on the secretory function of bovine adrenal chromaffin cells in culture were studied. Treatment of chromaffin cells with IAP resulted in an increase in both basal release of catecholamine and evoked-release by either acetylcholine (ACh) or high K+. In the dose-response curve for ACh-evoked release, IAP treatment produced an increase of the maximal response without affecting the half-maximal concentration of ACh. When the cells were permeabilized with digitonin after IAP-pretreatment, Ca2(+) dependent exocytosis was markedly increased where the affinity of exocytosis for Ca2+ was augmented. These findings suggest that IAP-sensitive GTP-binding protein (or proteins) directory controls the Ca2(+)-triggered process in the machinery of exocytosis by modulating the affinity for Ca2+ of its unknown target. PMID- 2325883 TI - Effect of unilateral nucleus basalis lesion on cortical and striatal acetylcholine and dopamine release monitored in vivo with microdialysis. AB - Cortical and striatal extracellular acetylcholine (ACh), choline (Ch), dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels were estimated in samples collected with microdialysis in halothane-anaesthetized rats which had received 0.6 microliter of ibotenic acid (5 micrograms/microliters) into the left nucleus basalis magnocellularis (microdialysis experiments were performed 3-4 weeks after the lesion). Samples were collected under basal (Ringer or Ringer including 10 microM neostigmine) and KCl (100 mM)-stimulated conditions. In the intact frontoparietal cortex and striatum, basal ACh (only detected under neostigmine perfusion) was in the 30 and 300 nM range, respectively. In the same conditions, Ch was in the 0.7 microM range in the cortex and in the 0.2 microM range in the striatum. The inclusion of KCl in the perfusion medium strongly enhanced cortical (greater than 7-fold) and striatal (greater than 10-fold) ACh. KCl only moderately increased striatal (65%) but not cortical Ch. In the lesion side, both basal and stimulated ACh were significantly reduced in the cortex (greater than 60%), but not in the striatum. Ch was not significantly changed in the cortex and striatum. The nucleus basalis lesion also produced a drop in extracellular levels of cortical and striatal DA (40% and 55%, respectively). Neither cortical nor striatal ACh levels were modified by a unilateral DA deafferentation (6 hydroxydopamine lesion into the medial forebrain bundle). However, the destruction of the intrinsic cortical ACh by injection of kainic acid into the frontoparietal cortex produced a 30% decrease in ACh. PMID- 2325884 TI - Electrochemical characterization of stimulated norepinephrine overflow in locus coeruleus-hippocampus double brain grafts grown in oculo. AB - Rat locus coeruleus-hippocampus double in oculo brain grafts were studied with high-speed electrochemical techniques to characterize stimulus-evoked overflow of norepinephrine. Local pressure ejections of KCl into the locus coeruleus (LC) portion of the double graft elicited electrochemical signals in the hippocampal portion that had NE-like reduction/oxidation current ratios. In contrast, electrical stimulation of the LC part of the double graft did not lead to consistently detectable signals in the hippocampal portion of the transplant. These data demonstrate that LC graft neurons are able to release NE in target tissues when stimulated in an appropriate manner, and that the time course and magnitude of the overflow of NE can be detected with sensitive high-speed electrochemical recording techniques. PMID- 2325885 TI - Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson's and Alzheimer's disease. AB - Elevated plasma cysteine to sulphate ratios were found in patients with Motor neurone disease (MND), Parkinson's disease (PD) and Alzheimer's disease (AD). Cysteine and sulphate were measured by colourimetric methods. Following recent discovery of a defect in sulphoxidation and sulphation of xenobiotics in these diseases, this finding confirms that endogenous sulphur metabolism is disturbed. The mean cysteine:sulphate ratios (x 10(3] in fasting early morning plasma were 506, 521 and 477 for MND, PD and AD whereas it was 96 for normal controls (P less than 0.001). This excess of cysteine thiol groups may interfere with neural protein function. The deficiency of sulphate ions may lead to reduced xenobiotic detoxification. PMID- 2325886 TI - Erythrocytes suppress calcitonin gene-related peptide- and vasoactive intestinal polypeptide-like immunoreactivities in cerebrovascular nerve fibers after subarachnoid hemorrhage. AB - Changes of calcitonin gene related-peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities (LI) in cerebrovascular nerve fibers on the dog basilar artery were immunohistochemically examined by using whole-mount preparations after single percutaneous injection of blood components into the cisterna magna. Blood components were prepared from autologous arterial blood. CGRP- and VIP-LI in cerebrovascular nerve fibers were highly suppressed after the injection of washed erythrocytes, but only moderately after the injection of platelet-rich or platelet-poor plasma. The results suggest that erythrocytes may suppress CGRP- and VIP-LI in cerebrovascular nerve fibers after subarachnoid hemorrhage. PMID- 2325887 TI - Sequential changes of potassium currents in Hermissenda type B photoreceptor during early stages of classical conditioning. AB - Classical conditioning of the marine snail Hermissenda can be produced in a single session of 50 pairings of light and rotation stimuli. Voltage clamp measurements of two outward K+ currents, IA and ICa2(+)-K+ were obtained from medial Type B photoreceptors that were isolated from the nervous system 1 day after animals were exposed to paired light and rotation stimuli or control procedures (Unpaired, or no exposure to light and rotation), ICa2(+)-K+ was found to be unchanged 18-30 h after 50 training trials. This result is consistent with a previous study where ICa2(+)-K+ was found to be unchanged after 50 light and rotation trials, although significantly reduced by 100 trials. In the present study 50 pairings of light and rotation produced a significant reduction in IA, suggesting an important role for this current in the earliest stages of classical conditioning. PMID- 2325888 TI - Low- and high-voltage-activated Ca2+ conductances in electrically excitable growth cones of chick dorsal root ganglion neurons. AB - Growth cone Ca2+ currents of chick dorsal root ganglion (DRG) neurons were recorded by a patch pipette located on the cell soma. Somatic and neuritic conductances were selectively blocked either with TTX and Cd2+ or by superfusing with isotonic sucrose using a laminar flow perfusion system. DRG growth cones were electrically excitable and growth cone Ca2+ currents were similar to Ca2+ currents described in DRG somata. In particular low-voltage-activated (LVA) Ca2+ conductances were well represented contrary to previous suggestions in other cell types. PMID- 2325889 TI - Effects of coenzymes Q2 and Q10 on the field potential of guinea pig olfactory cortex slices maintained in hypoxia. AB - The effects of exogenous CoQ2 and CoQ10 on field potentials were studied while brain slice preparations of guinea pig olfactory cortex were incubated in hypoxia. The potential amplitude, which diminished in hypoxia, recovered when the slices were superfused with solutions containing CoQ2 and CoQ10. Adenosine triphosphate (ATP) levels in the slices duplicated the experimental results of the potential amplitude. The effects of these ubiquinones on potentials measured in hypoxia were suppressed when the slices were incubated with a barbiturate solution. PMID- 2325890 TI - Analysis of the cardiovascular changes evoked by microinjection of NaCl into the nucleus tractus solitarii of rats: evidence for a Na+/Ca2+ relationship. AB - The effect of various ionic solutions microinjected into the nucleus tractus solitarii (NTS) on blood pressure, heart rate and respiration rate was investigated in urethane-anesthetized rats. Unilateral microinjection of solutions containing NaCl (154 mM), NaCl (154 mM) and KCl (2.8 mM) or NaNO3 (154 mM) into a restricted area of the NTS evoked acute decreases in blood pressure, heart rate and respiration rate. However, calcium chloride (0.36-3.3 mM), present in the microinjection solutions, reduced the decrease in all 3 recorded parameters in a concentration-dependent manner. A disturbance in the Na+/Ca2+ ionic ratio may account for the changes evoked by the administered solutions. These results indicate the presence of a restricted area in the NTS which is sensitive to changes in some vegetative functions. PMID- 2325891 TI - Ionic currents in retrogradely labeled trigeminothalamic neurons in slices of rat medulla. AB - We have recorded the ionic currents of identified trigeminothalamic neurons in medulla slices in vitro. Trigeminothalamic cells were first retrogradely labeled by injecting fluorescent latex microspheres in the thalamus of a 7- to 10-day-old rat. Two days later, thin slices (80-100 microns) were prepared from the lower medulla of the injected rat. Whole cell recordings were performed on the labeled cells located in the spinal trigeminal nucleus caudalis using the patch clamp technique. The voltage dependent inward sodium, inward calcium and outward potassium currents are qualitatively similar to those obtained from the enzymatically dissociated trigeminothalamic neurons. Successful application of this thin slice method opens the opportunity of studying synaptic circuitry in the trigeminothalamic system. PMID- 2325892 TI - Electrocorticographic characterization of chronic iron-induced epilepsy in rats. AB - Electrocorticograms were recorded from rats which were unilaterally injected with ferrous chloride solution into the sensorimotor cortex to induce chronic epileptic activity. All of the iron-injected rats showed isolated spikes near the injection site and in the contralateral cortex immediately after the injection. The injection produced 3 kinds of responses in the rats according to the frequency of the isolated spikes. Spike and wave complexes appeared bilaterally approximately 30 days or more after the injection in the rats in which the frequency of the isolated spikes was dominant on the side ipsilateral to the injection site or nearly equal on the two sides. These results suggest that there are at least 2 stages in the development of chronic iron-induced epilepsy. PMID- 2325893 TI - The rat pineal N-acetyltransferase rhythm persists after a five-hour, but disappears temporarily after a seven-hour advance of the light-dark cycle: a six hour shift may be a turning point. AB - After a 5-h advance of a lighting regime with 12 h of light and 12 h of darkness by shortening of one dark period, the rat pineal N-acetyltransferase (NAT) rhythm was retained, though at the beginning in a changed waveform, and re-entrained to the shift within 5 to 6 cycles. After a 7-h advance of the regime, the NAT rhythm faded away between the 2nd and 4th cycle and re-entrained to the shift within 7 cycles. A 6-h advance of the lighting regime might thus be a turning point for the persistence or temporal disappearance of the NAT rhythm. PMID- 2325894 TI - Responses of hypogastric nerve afferent fibers to uterine distension in estrous or metestrous rats. AB - The response of afferent fibers in the distal end of the cut hypogastric nerve to distension of the uterus to various pressure levels was investigated in anesthetized virgin female rats on two different days of the estrous cycle (estrus or metestrus). Whereas relatively intense levels of uterine distension produced an increase in afferent activity in a pressure-dependent manner in both stages of the estrous cycle, the minimal pressure necessary to activate the fibers was significantly less on the day of estrus. These results suggest that hypogastric nerve afferent fibers are more likely to respond to potentially damaging uterine stimuli during the time when such responsiveness would be most important for reproductive success. PMID- 2325895 TI - Slowly adapting type I mechanoreceptor discharge as a function of dynamic force versus dynamic displacement of glabrous skin of raccoon and squirrel monkey hand. AB - The effects of dynamic force and dynamic displacement on single unit discharge rate during ramp stimulation were examined in 10 raccoon and 8 squirrel monkey slowly adapting Type I (SAI) mechanoreceptive afferent fibers, all having receptive fields on glabrous skin of the hand. In all 18 cases, power function exponents were higher for effects of dynamic displacement than for effects of dynamic force on discharge frequency. Thus, these SAI mechanoreceptors are more sensitive to variations in dynamic displacement than to variations in dynamic force. This differential sensitivity may be explained by the fact that the relationship between dynamic force and dynamic displacement is, itself, nonlinear, dynamic displacement being a power function of dynamic force, with exponents less than 1.0. PMID- 2325896 TI - Changes of activity in lumbar preganglionic neurones during slow urinary bladder filling in the cat. AB - The hypothesis was tested that sympathetic neurones projecting to the pelvic organs are excited during the collecting phase of the urinary bladder and inhibited when the intravesical pressure is beyond micturition threshold. Activity in single lumbar sympathetic preganglionic neurones projecting in the lumbar splanchnic nerves was measured when intravesical pressure was increased by slow filling at 2 ml/min in anaesthetized cats. Nine of 10 neurones tested were excited in a graded manner up to an intravesical pressure of 50 mmHg and during isovolumetric bladder contractions. On the basis of these quantitative results the hypothesis was refuted. The functional implications are discussed. PMID- 2325897 TI - Influence of retinal lesions on grating acuity of the cat. AB - Grating acuity was investigated behaviorally in the cat. Retinal lesions of increasing diameter centered on the area centralis were made by photocoagulations in one eye, while the intact eye was used as control. Lesion size evaluated from fundus photographs was precisely correlated with the anatomical lesion size measured in retinal whole mounts. Grating acuity improved with increasing grating area in cats with intact retinae and after small (less than 3 degrees diameter) retinal lesions but not after large lesions (greater than 4 degrees diameter). Overall, grating acuity clearly decreased when lesions became larger than 4 degrees in diameter. The acuity-eccentricity relationship closely fits the cutoff frequency of brisk sustained cells at the corresponding eccentricities. PMID- 2325898 TI - Which mechanisms account for the sensory neuron blocking action of capsaicin on primary afferents in the rat urinary bladder? AB - In the rat isolated bladder, capsaicin produced a concentration-dependent contraction, shown previously to depend upon transmitter release from peripheral endings of primary afferents. When using low concentrations (30-300 nM) of capsaicin, exposure to a second and third dose of capsaicin produced smaller responses than the first application, although a subsequent challenge with 10 microM capsaicin still elicited a contraction which was not reduced as compared to the response produced by the first exposure to a low dose of capsaicin. Capsaicin also evoked a prompt outflow of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI), taken as a marker for sensory nerve activation. A second or third application of a submaximal concentration of the drug was ineffective, although a subsequent challenge with 1 microM capsaicin was effective. These findings indicate that neuropeptide depletion does not necessarily account for the early stage of capsaicin 'desensitization' of primary afferents. PMID- 2325899 TI - Perforant path kindling induces differential alterations in the mRNA levels coding for prodynorphin and proenkephalin in the rat hippocampus. AB - The effect of perforant path kindling on the levels of mRNAs coding for proenkephalin and prodynorphin in hippocampus and frontal cortex of rats was measured using RNA blot analysis. In rats showing stage 3 kindled seizures, after consecutive stimulation of the right perforant path, a decrease in the level of prodynorphin mRNA and an increase in levels of proenkephalin mRNA in the ipsilateral hippocampus was found. In addition, the levels of prodynorphin were also decreased in the contralateral hippocampus. No changes in the opioid peptide mRNAs were found in the frontal cortex of the animals. The altered mRNA levels in the hippocampus returned to normal 8 days following cessation of the electrical stimulation. However, at that time a single stimulus was still effective in producing stage 3 kindling seizures. These findings indicate that (1) the opioid peptide gene expression in the hippocampus can be transynaptically altered by kindling of the perforant path and (2) that the opioid peptides may play a role in the development, but not in the maintenance of kindling. PMID- 2325900 TI - Two patterns of firing in human neocortical neurons. AB - Intracellular recordings were made in slices of human neocortex removed for surgical treatment of epilepsy. In response to prolonged suprathreshold current injection, regular spiking neurons (67.5% of sample) responded by repetitive firing throughout the stimulus from all membrane potentials. Bursting neurons (32.5% of sample) responded with a burst of 2-3 spikes which rode upon a voltage dependent slow depolarization. Bursting behavior was only observed from membrane potentials more negative than -65 mV. PMID- 2325901 TI - An electrophysiological study of the projections of putative sensory neurons within the myenteric plexus of the guinea pig ileum. AB - Conduction of action potentials in the processes of AH (afterhyperpolarizing) neurons has been examined in the myenteric plexus of the guinea-pig small intestine. AH neurons are a morphologically distinct class of myenteric neurons in which the action potentials are followed by long lasting afterhyperpolarizations and which usually lack fast synaptic inputs. These neurons have large smooth cell bodies and several long processes. We have used electrophysiological methods, combined with intracellular injection of the fluorescent dye 5(6)-carboxyfluorescein, to examine the directions of projection and lengths of axons of AH neurons. AH neurons of the myenteric plexus projected circumferentially in both directions from the cell soma for electrophysiologically determined average distances of 0.74 +/- 0.05 mm. Thus, the neurons span about 1.5 mm of the circumference of the intestine. About one quarter of the AH neurons had one, or rarely two, processes that ran anally after initially projecting circumferentially. All processes conducted action potentials, with average conduction velocities of 0.23 +/- 0.02 ms-1. PMID- 2325902 TI - Increased dopamine release in the nucleus accumbens of copulating male rats as evidenced by in vivo voltammetry. AB - This report describes the changes in extracellular levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) detected in the nucleus accumbens of male rats engaged in copulatory activity. They were monitored by using differential normal pulse voltammetry (DNPV) with electrochemically pretreated carbon fiber microelectrodes and numerical analysis of the catechol signal. The copulatory pattern displayed during the voltammetric recordings was similar to those recorded prior to surgery. Copulating animals showed a conspicuous increase in the DA and DOPAC electrochemical signals up to, respectively, 170% and 150% of baseline levels. This response was much attenuated when the experimental animals were exposed to either non-receptive castrated females or intact males. These data are consistent with the permissive role currently ascribed to the dopaminergic innervation of the n. accumbens in the selection and the initiation of behavioral adaptive sequences. PMID- 2325903 TI - The slow inhibitory postsynaptic potential in rat hippocampal CA1 neurones is blocked by intracellular injection of QX-314. AB - Intracellular recordings were made from CA1 pyramidal neurones in the rat hippocampus slice preparation. The recording electrodes contained potassium acetate (4 M) with or without the quaternary lidocaine derivative, QX-314 (50 mM). Both fast (f) and slow (s) inhibitory postsynaptic potentials (IPSP) were evoked by low-frequency orthodromic stimulation. The s-IPSP was rapidly reduced by QX-314 injection. It decreased along a similar time course to the dV/dt of the action potential (AP). The f-IPSP and excitatory postsynaptic potential were not significantly reduced in size at a time when the s-IPSP was virtually abolished by QX-314. It is concluded that conductance through the K+ channels which are coupled to GABAB receptors is readily blocked by QX-314, while the Cl- channels which are coupled to GABAA receptors and the cation channels coupled to the glutamate receptors are relatively resistant to the local anaesthetic. PMID- 2325904 TI - Noradrenergic mechanisms in the central amygdalar nucleus and gastric stress ulcer formation in rats. AB - Microinjections of noradrenaline (NA, 0.3, 3.0 and 30.0 micrograms) into the central amygdalar nucleus (CEA) produced dose-related attenuations of cold restraint (3 h at 4 degrees C) induced gastric ulcer formation in rats. On the other hand, stress ulcer aggravating effects were seen with beta-adrenoceptor antagonist, propranolol (10 micrograms) but not with the alpha-adrenoceptor antagonist, prazosin (1 and 10 micrograms). Moderate enhancements of gastric stress lesions were also seen with the NA release inhibitor clonidine (1 microgram) and the neurotoxin DSP-4 (25 micrograms). Further, pretreatment of rats with intra-amygdalar (i.am.) propranolol but not prazosin, antagonized and reversed the gastric cytoprotective effects of NA. The results indicate that beta adrenoceptor-mediated NAergic mechanisms at the level of the CEA are important for the maintenance of gastric mucosal integrity during immobilization stress. PMID- 2325905 TI - Intracellular mechanisms governing the acute phase of beta-endorphin secretion from the corticotrope in vitro. AB - It is not certain which protein kinase (A, C or both) is involved in the acute phase of beta-endorphin (beta-EP) release stimulated in the corticotrope by vasopressin (VP) and corticotropin-releasing factor (CRF). We have employed an isolated ovine anterior pituitary cell superfusion system to determine the dynamic effects of forskolin, a protein kinase A (PKA) stimulator, and phorbol 12 myristate 13-acetate (PMA), a protein kinase C (PKC) activator. Both secretagogues stimulated beta-EP release within 5 min and therefore both PKA and PKC are potential mediators of the acute phase of hormonal stimulation of the corticotrope. Pretreatment with PMA specifically desensitized the pituitary cell columns to subsequent PMA exposure while not significantly altering sensitivity to forskolin or 50 mM KCl. PMID- 2325906 TI - Who will care for the caretakers? PMID- 2325907 TI - Can health care costs be contained? AB - In order to control the future of health care in this nation, one has to understand the present. Grace gives a comprehensive picture of our present health care system with an eye to its costs and how nursing can contribute if the system is to be changed. PMID- 2325908 TI - Research in nursing education: yesterday--today--tomorrow. AB - Reilly gives us a highly personal account of the development of research in nursing education, bridging from the past to the present and on to the future. Ranging from Nightingale as statistician to the effects of doctor-nurse relations to the acceleration produced by various wars to the special nurses who strived to make research a natural process for the profession, Reilly makes us feel like we live along with her this part of our rich heritage. PMID- 2325910 TI - Reminiscences by Lulu Wolf Hassenplug, Dean Emeritus, School of Nursing, UCLA. Interview by Barbara J. Barnum. PMID- 2325909 TI - Health maintenance organizations: history, evolution, & survival. AB - It's hard to believe that HMOs are old enough to have a past, but Drew does an excellent job of reviewing their development and present status. Issues of cost, quality, and politics are covered in thoughtful and precise detail. What is the future of HMOs? Drew draws some interesting conclusions. PMID- 2325911 TI - Doctoral preparation of nursing faculty. AB - Is the doctorate necessary for all nurse educators? Should nurse educators hold a doctorate or is a non-nursing doctorate acceptable? The authors report on a survey which looked at information concerning the number of doctorally prepared nursing faculty and the institutional requirement of a doctorate as the terminal degree in nursing. PMID- 2325912 TI - Teaching injection technique: nursing students as subjects. PMID- 2325913 TI - Nursing informatics: a model curriculum for an emerging role. AB - The authors delineate the emerging role of the nurse as Information Systems Specialist and describe a prototype educational program in Nursing Informatics which is designed to prepare nurses for this role. Major duties, knowledge required, and resulting interactions related to the role are discussed in relation to the curriculum design and course content. The projected impact of this model program is also addressed. PMID- 2325914 TI - The Harlaxton experience: transcultural nursing education in the United Kingdom. AB - Studying nursing in the English countryside provides valuable insight for students taking community health nursing at the University of Evansville's Harlaxton College campus in Grantham, England. Students gain understanding of new, creative methods of nursing while learning to appreciate the value of time honored approaches to health care delivery. This program can serve as a model particularly for those wishing to study transcultural nursing and alternative ways of delivering nursing and health care. PMID- 2325915 TI - Organizational culture: helping new graduates adjust. AB - New graduates' successful adjustment to their work situation influences their ability to apply the principles and concepts they have learned in school. The author suggests that an understanding of organizational culture can facilitate this adjustment by assisting new graduates to select a work group suitable for them, to adapt to this group, and to bring about change within the group. Suggestions for teaching students about organizational culture are included. PMID- 2325916 TI - An assessment of academic nursing centers. AB - The authors discuss the status of academic nursing centers. Included are data on the age, location, population served, and sources of financial support for these centers. In addition, the authors assess the centers' ability to accomplish the purposes of faculty practice, student education, nursing research and community service. Implications for developing academic nursing centers are presented. PMID- 2325917 TI - How well are we teaching leadership and management? PMID- 2325918 TI - National Council Licensure Exam. PMID- 2325919 TI - Nuclear war and nursing. PMID- 2325920 TI - The advantages and disadvantages of interprofessional gerontic education. PMID- 2325921 TI - Reflection and professional education: art, science, and competency. AB - Reflection is the process of reviewing one's repertoire of clinical experience and knowledge to invent novel approaches to complex clinical problems. Reflection also provides data for self-evaluation and increases learning from experience. The author suggests several activities which are particularly useful in facilitating a reflective nursing practice. These activities may assist educators to encourage students' clinical competency. PMID- 2325922 TI - Medical care for Nicaraguan poor: making do with next to nothing. PMID- 2325923 TI - Anorexia nervosa and bulimia: incidence and diagnosis. AB - The incidence of eating disorders is increasing at an alarming rate. The clinician who sees many female teenagers and young women in the course of practice is a prime candidate for identifying and providing early diagnosis and communication with the anorexic or bulimic client. Vigilance when assessing the client's physical, psychological, personal and family-history status will increase case-finding for eating disorders at an earlier point in the disease. PMID- 2325924 TI - The impact of group reminiscence counseling on a depressed elderly population. AB - Elderly patients present an enormous challenge to the mental health care system. Statistics have shown a high rate of mental disorders, especially depression and suicide, among this population group. Reminiscing about the past has been theoretically linked to positive adjustment in old age. The purpose of this study was to assess the effect of group reminiscence counseling on the level of depression of elderly women residing in nursing homes. A sample of 60 women 65 years and older participated in this study. Subjects were randomly classified into two experimental groups and one control group. An interview schedule that included demographics and Beck's Depression Inventory was employed to collect data. Chi-square analysis was used to test the homogeneity of the three groups with respect to their demographic characteristics. Analysis of data using the analysis of variance method showed that the differences between the levels of depression before and after the reminiscence counseling sessions were statistically significant in the younger subjects (65 to 74 years), and insignificant in the older subjects (over 74 years). Findings imply that group reminiscence counseling did have an effect on the elderly's level of depression. From the findings of this study, implications and recommendations are drawn. PMID- 2325925 TI - Clinical nurse specialist and nurse practitioner core curricula survey results. AB - The American Nurses' Association's Council of Clinical Nurse Specialists and Council of Primary Health Care Nurse Practitioners conducted a survey of all graduate nursing programs in the United States that prepare nurse practitioners and/or clinical nurse specialists. One hundred eight schools responded (73.5 percent), yielding data on 317 programs that could be further analyzed. For the 60 NP and 195 CNS programs analyzed, information was obtained on the following: required courses, number of hours of the required courses, students' clinical training settings and graduates' employment settings. Findings revealed marked similarity between the core curricula of NP and CNS graduate programs. The only significant differences found were that NP programs placed greater emphasis on pharmacology, primary care, physical assessment, health promotion, nutrition and history-taking in their curricula. In both the student clinical settings and graduate employment settings, NPs focused on primary care settings while CNSs focused on secondary or tertiary care settings. Based on the marked similarities between the core curricula of NP and CNS graduate programs, it is suggested that further investigations be conducted to determine whether objectives and/or teaching methods differ, and to further investigate the effects of practice setting on role development. Further, it is suggested that NPs and CNSs continue to interact through forums and conferences to continue the evolution and definition of graduate nursing education and advanced practice. PMID- 2325926 TI - Are nurse practitioners prepared for the AIDS epidemic? AB - Treatment of HIV-infected individuals will become a regular part of mainstream medical practice because of the increasing numbers of infected persons, the geographical dispersion of the disease, and the routine nature of much of the care required by seropositive patients. Nurse practitioners, like other health care professionals, need to be willing and able to provide such primary care. One hundred sixty-five NPs constituted an opportunity sample that was surveyed using an instrument that had been adapted from one used successfully in studies of other health professionals. The instrument consisted of 80 forced-answer and six open-ended questions. The response rate was 63 percent. It was found that nurse practitioners believed there was moderate risk of occupational contraction of HIV. NPs were more likely to agree on activities they believed to be of low risk than about the danger of perceived higher-risk activities. The respondents judged themselves as fairly competent in their ability to provide counseling and information to patients about HIV and risk-reduction. Half believed that their lack of knowledge was the biggest barrier to providing care to HIV-infected persons. Eighty-five percent thought courses on the medical aspects of AIDS were necessary, and 78 percent wanted courses in the social, ethical and legal implications of the disease. This study shows that there is a widely perceived need for continuing education on both medical and social aspects of AIDS in order to enable nurse practitioners to play a greater role in primary care provision for persons with AIDS. PMID- 2325927 TI - Liquid crystal thermographs: 'best choice' for body-heat measurement. PMID- 2325928 TI - Community care: the elderly. Nursing in a day hospital. PMID- 2325929 TI - Wound management--cosmetic camouflage. PMID- 2325930 TI - Diabetes--the benefits of exercise. PMID- 2325931 TI - One day at a time. PMID- 2325932 TI - Research series 4. Evaluating and implementing. PMID- 2325933 TI - 'Just' a health worker? PMID- 2325934 TI - Oxford: aiming for excellence. PMID- 2325935 TI - Community nursing. Teamwork in primary care. PMID- 2325936 TI - Career profile: haemophilia research. PMID- 2325937 TI - Who dares to differ? PMID- 2325938 TI - Community care: the elderly. Abuse of elderly people. PMID- 2325939 TI - Community care: the elderly. Crisis and the confused elderly. PMID- 2325940 TI - Antagonism of morphine analgesia by nonopioid cold-water swim analgesia: direct evidence for collateral inhibition. AB - The demonstrated existence of opioid and nonopioid forms of pain control has raised questions as to how they interact. Previous indirect evidence suggests that activation of one system inhibited the activation of the other. The present study assessed this directly using morphine as an opiate form of analgesia and continuous cold-water swims (CCWS, 4 degrees C, 2 min) as the nonopioid form. A significant reduction in morphine (8 mg/kg, SC) analgesia on the tail-flick test was observed if rats were acutely exposed to CCWS immediately prior to morphine administration. The inability of naloxone (10 mg/kg, SC) to reduce CCWS analgesia verified its nonopioid nature. The antagonism of morphine (3 mg/kg, SC) analgesia was greater following preexposure to 2 min of CCWS than 1 min of CCWS. CCWS was also more effective in antagonizing analgesia induced by the 3 mg/kg than the 8 mg/kg dose of morphine. The antagonism of morphine analgesia by CCWS was dependent upon the temporal patterning of stimulus presentation: exposure to CCWS 20 or 60 min prior to morphine failed to alter subsequent morphine analgesia. A significant reduction in analgesia induced by intraperitoneal administration of morphine (10 mg/kg) was also observed when CCWS was presented immediately prior to injection, suggesting that pharmacokinetic factors such as altered drug absorbance by CCWS-induced vasoconstriction do not appear to explain these effects. These data provide direct support for the existence of collateral inhibitory mechanisms activated by CCWS and morphine, and suggests that these opioid and nonopioid forms of analgesia do not function synergistically, but instead involve some form of hierarchical order. PMID- 2325941 TI - Decreased intracranial self-stimulation in a new animal model of endogenous depression. AB - Neonatal treatment of rats with clomipramine may produce adult animals which model endogenous depression. We report here that a major factor of depression in humans, the diminished capacity for pleasure, appears present in these rats. At age 7 months, bar-press responding for rewarding hypothalamic stimulation is reduced across a range of intensities. At age 4 or 5 months this effect is not seen, although other behavioral abnormalities are present at the younger age. The delayed onset of diminished intracranial self-stimulation may relate to the gradual insidious onset of endogenous depression in humans. PMID- 2325942 TI - Procedure- and age-dependent hyperactivity in a new animal model of endogenous depression. AB - We have replicated the findings of Mirmiran and colleagues that neonatal administration of the antidepressant clomipramine (CLI) to male rats results in hyperactivity in open-field tests in adulthood. We report that this effect does not reliably occur in a "Digiscan" activity device. The difference in effect between the two activity measuring devices may be due to more stress being present in the open-field test, and we propose that the CLI-treated rats may be more reactive to stress. This hypothesized enhanced reactivity to stress may be similar to the proposed vulnerability of depressed humans to stress. In addition, we have found that the open-field effect does not occur until the rats are at least 4 months old; this delayed effect may be analogous to the progressive onset of endogenous depression in humans. PMID- 2325943 TI - Diminished sexual activity in a new animal model of endogenous depression. AB - Our laboratory has proposed a new animal model of endogenous depression. The proposal is that in rats neonatal clomipramine (CLI) produces adult animals that model endogenous depression. Diminished sexual activity is a salient behavioral abnormality found in endogenous depression. This suggests that an animal model of endogenous depression should show diminished sexual activity. We report here a test of the prediction that after neonatal treatment with CLI, adult male rats show decreased sexual activity. We found that after neonatal CLI, adult male Long Evans rats had a pervasive diminution of sexual activities including decreased mounts, intromissions, ejaculations, and increased mount latencies and postejaculatory pause. Sprague-Dawley and Wistar strains also tended to show decreased intromissions and ejaculations, but their baseline sexual activity was too low to give interpretable data. The results with the sexually active Long Evans strain are consistent with the hypothesis that neonatal CLI produces adult rats that model human endogenous depression. PMID- 2325944 TI - REM sleep abnormalities in a new animal model of endogenous depression. AB - Endogenous depression has reliable REM sleep abnormalities. These include a short REM latency, frequent sleep onset REM periods, and after REM sleep deprivation (RSD), an abnormal temporal course of REM rebound in the presence of a normal total REM rebound. The reliability of these abnormalities suggests that they ought to be present in an animal model of endogenous depression. In 1982, we proposed a new animal model of endogenous depression. Our hypothesis is that in rats neonatal clomipramine (CLI) will produce adult animals that model endogenous depression. In this study we tested the prediction that after neonatal treatment with CLI, adult rats will show the above three REM sleep abnormalities of human endogenous depression. We found that neonatal treatment with CLI produced rats that at age 6 months had shorter REM latency, more sleep onset REM periods than control rats, and after RSD, had an abnormal temporal course of REM rebound in the presence of a normal total REM rebound. The finding of these REM sleep abnormalities supported the validity of the animal model of endogenous depression. PMID- 2325946 TI - Claiming the computer. PMID- 2325947 TI - Moving to better health. PMID- 2325945 TI - Amphetamine- and morphine-induced feeding: evidence for involvement of reward mechanisms. AB - The present study examined the possibility that the increased feeding found following central and peripheral administrations of low doses of d-amphetamine (AMP) and morphine (MOR) may involve central reward mechanisms. In order to examine this possibility, the effects of these drugs on food selection and intake of foods that varied in palatability and nutritive content were determined. In addition, the importance of the nucleus accumbens (ACB), a critical structure for AMP and MOR reward, in these effects was determined. Results indicated that MOR increased the intake of preferred food regardless of nutritive content. In contrast, AMP was most effective at increasing the intake of preferred foods which contained carbohydrates. These effects were observed following systematic or intra-ACB administration of low doses of MOR and AMP. Together these findings implicate reward mechanisms in the expression of MOR- and AMP-induced feeding. It is further suggested that the feeding effects of MOR and AMP can be differentiated in paradigms where animals have a choice of several foods which may vary in palatability and/or nutritive content. The relevance of the present findings for our understanding of which elements of food and feeding behavior are coupled with ACB reward signals is also discussed. PMID- 2325948 TI - Dignity in dementia. PMID- 2325949 TI - Unions: policy makers of the nineties? PMID- 2325950 TI - Flying nurses need cover. PMID- 2325951 TI - Cervical news update. PMID- 2325953 TI - The DSSNY young professional. A report. PMID- 2325952 TI - In support of the rubber dam. PMID- 2325954 TI - Neuromuscular analysis in orthodontics. PMID- 2325956 TI - Hepatitis B as serious as AIDS. PMID- 2325955 TI - Computerized mandibular scanner evaluation following osteotomy surgery. PMID- 2325957 TI - On the concept of neuromuscular occlusion. PMID- 2325958 TI - Serum CA 125 levels in early pregnancy and subsequent spontaneous abortion. AB - CA 125 has been found in high concentrations in human amniotic fluid throughout gestation, with significant quantities seen in the decidua and chorion. Because disruption of the epithelial basement membrane of the fetal membrane or the decidua could theoretically lead to a rise in maternal CA 125 levels, this increase may be a predictor of subsequent spontaneous abortion of the fetus. A study was initiated to investigate whether a sudden rise in the serum CA 125 level might predict spontaneous first-trimester abortions. CA 125 levels of 101 pregnant women were evaluated 18-22 days from conception and 6 weeks from conception (a frequent time for spontaneous abortion) to determine whether there is a sudden increase (from baseline or early trimester levels) during the middle or late first trimester immediately before or at the time of abortion. The results indicated that although there was a definite correlation found between elevation of CA 125 and spontaneous abortion, the higher levels occurred early in the first trimester whereas the majority of abortions did not occur until much later, after fetal viability was established. Six of ten women with CA 125 levels of 150 U/mL or greater aborted, compared with four of 92 women with CA 125 levels less than 150 U/mL. One of 11 women pregnant after in vitro fertilization had a CA 125 level above 150 U/mL, and she aborted. PMID- 2325959 TI - Amoxicillin therapy for Chlamydia trachomatis in pregnancy. AB - For treating Chlamydia trachomatis cervical infection in pregnancy, the Centers for Disease Control guidelines recommend either erythromycin base or erythromycin ethylsuccinate. There is no alternate therapy. Because of compliance problems with erythromycin regimens due to gastrointestinal side effects, such an alternative is needed. For this reason, we compared, in an open trial, the efficacy and patient compliance of amoxicillin (500 mg three times a day for 7 days) with those of erythromycin base (500 mg four times a day for 7 days) in treating C trachomatis cervical infections during pregnancy. In the amoxicillin group, 63 of 64 women (98.4%) had negative cervical cultures after treatment, compared with 55 of 58 women (94.8%) treated with erythromycin base. Vertical transmission to the infants was assessed by culture and/or persistent or rising immunoglobulin G antichlamydial antibody. In the amoxicillin group, 37 of 39 infants (94.9%) had no evidence of chlamydial infection, compared with 32 of 36 infants (88.8%) in the erythromycin group. These differences were not significant. The frequency of side effects was higher with erythromycin base than with amoxicillin (15 versus 8%), although not significantly so. However, the frequency of stopping medication because of side effects was significantly higher with erythromycin base than with amoxicillin (13 versus 2%; P less than .006). These results suggest that amoxicillin may be an acceptable alternative treatment for chlamydial infections in pregnancy. PMID- 2325960 TI - A prospective comparison of hourly and quarter-hourly oxytocin dose increase intervals for the induction of labor at term. AB - Fifty-two women undergoing labor induction and vaginal delivery at term were randomized between two oxytocin infusion protocols, involving hourly versus quarter-hourly increases in dose. Potential differences were sought of duration of labor, amount of uterine activity generated, and amount of oxytocin required. Starting at 0.5 mU/minute, oxytocin infusion was increased regularly in small increments every hour or every 15 minutes, according to group assignment. No differences were observed in potentially confounding clinical and demographic factors between the groups, including time to ruptured membranes. There were no clinically or statistically significant differences found for the duration of any phase or stage of labor, quantitative assessment of uterine activity, incidence of hyperstimulation, or neonatal outcome. The average dose of oxytocin used was lower in the hourly than in the quarter-hourly, protocol (4.4 versus 6.7 mU/minute; P less than .005). Significantly fewer patients on the hourly protocol required a maximum infusion rate exceeding 8 mU/minute (P less than .05). More patients on the hourly protocol either had oxytocin discontinued completely or were maintained at 4 mU/minute or less during the active phase of labor (P less than .05 and P less than .001, respectively). We conclude that a slower rate of increase in oxytocin administration via continuous infusion results in no prolongation of any phase of induced labor, while permitting lower infusion rates of the drug. PMID- 2325961 TI - Use of magnesium sulfate to treat hyperstimulation in term labor. AB - Magnesium sulfate has been shown in vivo and in vitro to decrease the frequency of uterine contractions while maintaining the amplitude; we therefore decided to assess the use of magnesium sulfate infusion in cases of uterine hyperstimulation. The medical records were reviewed retrospectively for 37 term pregnant patients diagnosed as having uterine hyperstimulation during labor. None of them had medical or obstetric complications. Twenty-two of them received oxytocin augmentation for abnormal labor. Although the vast majority of these patients had a decrease of the hyperstimulation while being given the magnesium, 31.8% in the group receiving oxytocin alone (P less than .05). Fifteen additional patients received magnesium sulfate for uterine hyperstimulation although they were not receiving oxytocin; of these, 16.7% required cesarean delivery. This rate was no different from that of the patients who required labor augmentation, but was double the overall primary cesarean rate at our hospital. There appears to be a group of patients with abnormal uterine activity (either spontaneous or associated with oxytocin augmentation) that responds to treatment with magnesium sulfate. PMID- 2325962 TI - The relationship of abruptio placentae with maternal smoking and small for gestational age infants. AB - A population-based case-control study was conducted to examine the relationship between maternal smoking and the occurrence of abruptio placentae and to assess the joint relationship of smoking and small for gestational age (SGA) status with abruption. Cases (N = 1089) reported on Washington state birth certificates from 1984-1986 were compared with randomly selected births (N = 2323) from the same period. The occurrence of placental abruption was associated with both smoking (relative risk = 1.6; 95% confidence interval 1.3-1.8) and SGA status (relative risk = 2.6; 95% confidence interval 2.0-3.3). The association with SGA status was identical for smokers and non-smokers. Thus, the increase of SGA infants in women whose pregnancies are complicated by abruption is not explained by maternal smoking, and in some cases may result from placental dysfunction induced by the process of placental separation. PMID- 2325963 TI - Relationship of bacteriologic characteristics to semen indices in men attending an infertility clinic. AB - Bacteria can be isolated from most seminal fluid samples, but the significance of these microorganisms is uncertain because most men lack symptoms associated with bacterial infection of the reproductive tract. We obtained semen samples from 37 men attending a Special Infertility Clinic and assessed the relationship between seminal fluid microorganisms and seminal fluid analysis including sperm motility, morphology, and concentration; the numbers of polymorphonuclear leukocytes and other white blood cells; and the hamster zona-free oocyte sperm penetration assay. Aerobic and/or anaerobic bacteria were recovered from 36 of the 37 samples. One hundred eighty-eight isolates (113 aerobes, 74 anaerobes, and one yeast) were recovered, with a mean of 5.2 isolates per semen specimen. The microorganisms recovered from the samples included: coagulase-negative staphylococci (89%), viridans streptococci (65%), diphtheroids (86%), Peptostreptococcus sp (62%), Bacteroides sp (27%), Gardnerella vaginalis (19%), Lactobacillus sp (16%), Actinomyces sp (16%), Enterococcus (11%), and Veillonella (11%). Other microorganisms including group B streptococcus, Hemophilus, Escherichia coli, Mobiluncus, and Clostridium were each recovered from fewer than 10% of the specimens. When the microbiology of seminal fluid specimens with or without polymorphonuclear leukocytes was compared, the presence of polymorphonuclear leukocytes in the semen was not associated with the isolation of staphylococci (33 versus 25%), viridans streptococci (33 versus 28%), Bacteroides sp (17 versus 37%), or Peptostreptococcus (31 versus 33%) (P greater than .05 for each comparison). The proportion of semen samples yielding bacterial isolates was similar after categorization by normal motility (more than 60%), pyospermia (six or more leukocytes per 100 sperm), sperm concentration, morphology, and a normal sperm penetration assay (11% or more).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325964 TI - Perinatal outcome in triplet versus twin gestations. AB - The present study was conducted to determine whether triplet pregnancies are associated with a significantly worse perinatal outcome than twin pregnancies. Maternal and neonatal outcome was evaluated in 15 triplet and twin pregnancies that were matched for maternal age, race, type of medical insurance, delivery mode, parity, and history of previous preterm delivery. Preterm labor occurred significantly more often in triplet than in twin gestations (80 versus 40%), as did preterm delivery (87 versus 26.7%). Triplets had a significantly lower mean birth weight (1720 versus 2475 g) and gestational age at delivery (33 versus 36.6 weeks). In addition, 53.3% of triplet pregnancies but only 6.7% of twin pregnancies had one or more neonates with intrauterine growth retardation. Discordancy also occurred more frequently in triplets than in twins (66.7 versus 13.3%). The mean averaged neonatal hospital stay was significantly higher in triplets (29 versus 8.5 days), and triplets had a fivefold increased risk of requiring neonatal intensive care as compared with twins. However, there were no significant differences between the groups in maternal morbidity or major neonatal complications such as respiratory distress syndrome or intraventricular hemorrhage. We believe that these data will be useful in counseling patients with respect to the anticipated perinatal outcome of triplet pregnancies. PMID- 2325965 TI - Morbidity among breech infants according to method of delivery. AB - To determine whether vaginally born breech infants are at increased risk for morbid events as compared with breech infants delivered by cesarean, we studied 1240 singleton breech infants without congenital anomalies delivered in Northern California Kaiser Permanente Medical Care Program hospitals during 1976-1977. Medical record review provided information on indications for method of delivery, delivery complications and injuries, neonatal complications, and neurologic sequelae up to 4 years of age. The relative risk estimates for asphyxia (1.0; 95% confidence interval 0.7, 1.4), head trauma (1.6; 95% confidence interval 0.2, 17.0), neonatal seizures (0.8; 95% confidence interval 0.1, 7.1), cerebral palsy (1.6; 95% confidence interval 0.2, 17.4), and developmental delay (2.0; 95% confidence interval 0.9, 4.4) for vaginally born compared with cesarean-delivered infants indicated that vaginally born infants were not at increased risk for these outcomes. We used multiple logistic regression to control for confounding variables. The adjusted relative risk estimate for the combined-outcome category of head trauma, neonatal seizures, cerebral palsy, mental retardation, or spasticity was 0.5 in vaginally delivered infants (95% confidence interval 0.1, 3.2). When all morbid outcomes were considered in combination, the adjusted relative risk estimate was 0.9 for vaginally delivered infants (95% confidence interval 0.6, 1.4). PMID- 2325966 TI - Transfer of ceftizoxime surpasses that of cefoperazone by the isolated human placenta perfused in vitro. AB - The transfer of cefoperazone and ceftizoxime across the human placenta was compared using the in vitro, bidirectionally perfused human placental lobule. The mean (+/- SEM) clearance indices for ceftizoxime and cefoperazone were 0.124 +/- 0.02 and 0.037 +/- 0.01, respectively (P = .0013). Cefoperazone concentration plateaued at a fetal concentration of 4-5 micrograms/mL in a recirculating perfusion system. No evidence of a decreasing slope of ceftizoxime transfer to the fetal compartment was noted after 60 minutes of perfusion. In a closed-closed perfusion system with equal concentrations of ceftizoxime in each compartment, a 1.1:1 fetal gradient was noted. These data indicate that ceftizoxime crosses the placenta significantly better than does cefoperazone and support our in vivo study documenting preferential concentration of ceftizoxime in the fetal compartment. PMID- 2325967 TI - Evaluation of a minimal-incision pubovaginal suspension as an adjunct to other pelvic-floor surgery. AB - In September 1987, Gittes and Loughlin first described a minimal-incision pubovaginal suspension as a modification of the Pereyra needle suspension urethropexy. Thirty-four women who underwent the minimal-incision urethropexy procedure were studied for up to 13 months postoperatively. Although 21 patients also had the anterior vaginal wall opened to perform concomitant pelvic-floor surgery, the principles of minimal suprapubic incision, full-thickness vaginal sutures, and no dissection of endopelvic fascia were followed strictly in all 34 cases. With a mean follow-up of 9.5 months, the objective cure rate was 91% and subjectively, 97% of the patients were either cured or improved. This technically simpler procedure is effective for treating genuine stress urinary incontinence in women who also require surgical repair of other pelvic-floor defects. PMID- 2325968 TI - Exercise and incontinence. AB - Three hundred twenty-six women filled out questionnaires to assess the relationship between exercise and incontinence. Two hundred ninety participants stated that they exercised regularly. Overall, 152 (47%) noted some degree of incontinence, which correlated positively with the number of vaginal deliveries (P less than .0005). Eighty-seven exercisers (30%) noted incontinence during at least one type of exercise. Incontinence exclusively during exercise was seen in only one woman. Exercises involving repetitive bouncing were associated with the highest incidence of incontinence. Seventeen incontinent exercisers (20%) stopped an exercise because of incontinence, whereas 16 (18%) changed the way a specific exercise was done and 48 (55%) wore a pad during exercise. Thirty-five percent had discussed their incontinence with a health care professional. These data suggest that incontinence during exercise is a common, although little known, problem. In addition to the behavioral adaptations which women initiate on their own, surgical and nonsurgical treatments may be of benefit. PMID- 2325969 TI - Urinary incontinence following radical vulvectomy. AB - Although incontinence has been reported after radical vulvectomy, its relationship to operative technique, anatomy, and treatment has not been defined. Twenty-one patients having vulvectomies for vulvar cancer were prospectively evaluated preoperatively and postoperatively with urodynamic function studies. A portion of the urethra was removed in four patients undergoing radical vulvectomy, and 14 had a vulvectomy excision that came within 1 cm of the distal urethra. Six patients (28%) developed a change of continence, with three developing total incontinence, two stress incontinence, and one urge incontinence. All four patients who had a portion of the urethra excised developed stress or total incontinence. The other two patients with incontinence (one total, one urge) had the vulvectomy excision that came close to the urethra. No patient had a change in continence when surgery did not involve or come close to the urethra. When the four patients with a distal urethral resection were compared with patients in whom the urethra was not excised, there was a significant decrease postoperatively in functional urethral length (P less than .0001), anatomical urethral length (P less than .0001), and distal urethral pressure transmission ratios in Q3 (P = .004), Q4 (P = .02), and Q5 (P = .005); but no difference in urethral support (Q-tip test), flow rates, residual urine, bladder capacity, maximal urethral pressure, resting closure pressure, or squeeze pressure. Histologic examination of urethral specimens demonstrated that a portion of the compressor urethrae muscle was often excised. Radical vulvectomy by itself does not cause incontinence, but it would appear that removal of a portion of the urethra increases the chance of incontinence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2325970 TI - Case-control study of cancer of the vulva. AB - A case-control study of 209 vulvar cancer patients and 348 community controls allowed assessment of risk factors for this rare tumor. As with cervical cancer, risk increased with the number of reported lifetime sexual partners, with five or more partners associated with two- to threefold increases in risk compared with zero to one partner. This factor largely explained the associations of risk with early age at first intercourse and low socioeconomic status. An independent association, however, was noted between vulvar cancer and a history of genital warts (relative risk 15.2; 95% confidence interval 5.5-42.1). Women who reported a previous abnormal Papanicolaou smear were at excess risk (relative risk 1.8), as were current smokers (relative risk 2.0). A significant interaction was noted between smoking and genital warts, with women reporting both having 35 times the risk of those with neither factor. Menstrual, reproductive, and hygiene factors were generally unrelated to risk. The relationships with sexual factors and genital warts support a common etiology for cervical and vulvar cancers. Future studies should focus on the etiologic agents for genital warts--the human papillomaviruses--and their enhancement by other factors, especially smoking and/or immune deficiencies. PMID- 2325971 TI - Loop diathermy cone biopsy. AB - A technique for cone biopsy using loop diathermy is presented. The diathermy loop consists of an insulated shaft attached to an insulated transverse or U-shaped arm, to which the loop wire is attached. The diathermy power is supplied by an electrosurgical unit. Among the first 50 cases, the mean age was 41.6 years; 72% of the cases were reported as cervical intraepithelial neoplasia III and 6% as microinvasive carcinoma. The mean length of the cone was 20.2 mm and the mean weight 3.9 g. Only 10% of the cones were reported as incompletely excised. No major complications were observed, and minor complications were reported in four patients (8%). We found this technique to be quick, simple, and economical. It provides a good histologic specimen with a low incidence of short-term morbidity. PMID- 2325972 TI - Nomograms for rapid estimation of intravascular intrauterine exchange transfusion. AB - Fetal exchange transfusion is complicated by the fact that vascular access must be maintained while the number of exchanges needed to achieve a desired post transfusion hematocrit is calculated. A rapid method for estimating the number of exchange transfusions would greatly simplify fetal exchange transfusion for blood group isoimmunization. In this report, we present a graphic method for determining the number of exchange transfusions necessary to achieve a post transfusion hematocrit of 45%, using a nomogram for 5- and 10-mL exchange transfusion volumes. PMID- 2325973 TI - Indiana pouch continent urinary reservoir in patients with previous pelvic irradiation. AB - Little information exists on the use of continent urinary reservoirs in patients with previous pelvic irradiation. We report the use of the Indiana pouch urinary reservoir in ten women with a history of pelvic irradiation for cervical cancer, of whom eight underwent a total pelvic exenteration for recurrent pelvic tumor and two had diversion for radiation-induced vesicovaginal fistula. All ten women achieved daytime continence, with a median time between catheterizations of 4.5 hours and a median pouch capacity of 500 mL. There was no evidence of leakage from the reservoir or significant ureteral reflux or obstruction on postoperative radiographic evaluation. No patient has required reoperation or had significant postoperative complications with the technique described. PMID- 2325974 TI - Survey of maternal-fetal medicine subspecialists: professional activities, job setting, and satisfaction. PMID- 2325975 TI - An analysis of closed obstetric malpractice claims. PMID- 2325976 TI - Screening for coronary disease in small companies. PMID- 2325978 TI - The who, what, why, where and when of screening. PMID- 2325979 TI - 'Her work is completely satisfactory...'. PMID- 2325977 TI - Cholesterol screening in the workplace. PMID- 2325980 TI - The law and your pay packet. PMID- 2325981 TI - Training for health. PMID- 2325982 TI - The challenge of change. PMID- 2325983 TI - Work experience in OH nursing education. PMID- 2325984 TI - Screening takes to the road. PMID- 2325985 TI - AIDS update. PMID- 2325987 TI - The case of the overly stimulating mall. PMID- 2325986 TI - The B.I.G. problem. Then and now. PMID- 2325988 TI - The season for Lyme disease: should Ohio physicians be concerned? PMID- 2325989 TI - Managing controlled drugs in the office. PMID- 2325990 TI - Patient satisfaction in oculoplastic surgery. AB - Patient satisfaction in oculoplastic surgery was evaluated through questionnaires sent to patients, referring physicians, and oculoplastic surgeons. Two oculoplastic surgical procedures, cosmetic blepharoplasty and acquired blepharoptosis treatment, were analyzed. One hundred forty-five patients and 85 referring physicians of the practices of five oculoplastic surgeons were questioned. Sixty-nine additional oculoplastic surgeons were also surveyed. The results of treatment were consistently emphasized as the most important factor in patient satisfaction, a finding that contrasted greatly with the decreased emphasis on the cost of treatment. This implies that patients value the quality of medical care and are willing to pay for it. The preference of patients contrasts sharply with the trend of government and third-party payers to emphasize cost containment at the possible sacrifice of quality of care. The surveys also showed that pain and discomfort and office waiting time are more important to patient satisfaction than oculoplastic surgeons realize and that the surgeons will have to address these issues in order to improve satisfaction. Also, there is a falloff of surgeon-patient communication postoperatively which is less satisfying to patients and recognized, but not acted on, by surgeons. Therefore, more postoperative surgeon-patient communication by telephone is also likely to improve patient satisfaction. PMID- 2325991 TI - Limbal anesthesia for cataract surgery. AB - We present a new technique for the administration of anesthesia in cataract surgery. The technique consists of injecting 0.5 ml of locally-acting anesthetic subconjunctivally (or sub-Tenon's) along the superior limbal border. Using this method, we performed extracapsular cataract extraction (ECCE) with and without posterior chamber intraocular lens (PC-IOL) implantation or secondary PC-IOL implantation on 176 cataract patients. Anesthesia was successfully induced in the majority of these patients and all surgeries were carried out successfully with no major complications. Voluntary eye movements remained but did not interfere with surgery. On the contrary, they helped expose certain surgical sites. This new anesthetic method for cataract surgery is simple and minimizes complications attributed to other blind anesthetic techniques. PMID- 2325992 TI - Factors associated with conjunctival intraepithelial neoplasia: a case control study. AB - Familial and environmental factors may play a role in the development of conjunctival intraepithelial neoplasia (CIN). Nineteen patients with biopsy proven CIN completed a questionnaire to evaluate possible predisposing factors. Nineteen age-matched and sex-matched controls completed questionnaires and received slit-lamp examinations. Factors associated with a relatively increased risk of developing CIN included exposure to petroleum products, heavy cigarette smoking, light hair and ocular pigmentation, and family origin in the British Isles, Austria or Switzerland. Non-office and nonprofessional workers were more likely to develop conjunctival intraepithelial neoplasia (p = .05), as were those who were not college graduates (p = .07). PMID- 2325993 TI - Pharmacological modulation of human subconjunctival fibroblast behavior in vitro. AB - The response of human subconjunctival fibroblasts to a variety of pharmacological agents was evaluated utilizing a novel in vitro wound assay and a separate proliferation assay. Both colchicine and cytochalasin B dramatically arrested wound closure at concentrations greater than or equal to 0.01 micrograms/ml and 2 micrograms/ml, respectively (p less than 0.05). At lower doses these drugs altered fibroblast morphology and inhibited directed cell migration. Dexamethasone and 6-MP delayed wound closure at concentrations greater than or equal to 100 micrograms/ml and 1000 micrograms/ml, respectively (p less than 0.05). Effective antiproliferative agents, in order of decreasing potency (based on unit weight), were Cytarabine (cytosine arabinoside), doxorubicin (Adriamycin), colchicine, 5-fluorouracil, cytochalasin B, cyclosporin (Sandimmune), 6-mercaptopurine, and dexamethasone. The antiprotease agents and methotrexate were ineffective as determined by both assays. We conclude that the wound assay is well suited for rapid screening of drugs for their effect on fibroblast morphology, motility, and proliferation, and that colchicine and cytochalasin B, in doses well below those documented to produce ocular toxicity, are effective in inhibiting directed migration and proliferation of subconjunctival fibroblasts in vitro. Differences in mechanism, onset of action, therapeutic range, and cytotoxicity of drugs could be exploited in controlling ocular fibroblast behavior in vivo. PMID- 2325994 TI - The effect of topical dexamethasone and preoperative beta irradiation on a model of glaucoma fistulizing surgery in the rabbit. AB - We studied the effect of topical dexamethasone (1%) and preoperative beta irradiation on a model of glaucoma fistulizing surgery in the rabbit. Intraocular pressure and gross facility of aqueous outflow following surgery were not influenced by either treatment, although blebs persisted longer in the irradiated eyes. Steroids reduced clinically observable inflammation as well as the number of inflammatory cells identifiable by microscopy. Fibroblast production temporarily slowed, and ultra-structural examination demonstrated lipid-filled vacuoles and dilated mitochondria in these eyes. Also, the scar was thinner at 24 days. Beta irradiation delayed wound healing and the scar was thinner in the early postoperative stages, but the light microscopic appearance of the scar was unaltered at 59 days. Inflammation was more pronounced initially, with abundant fibrin in the wound. Recovery of the conjunctival epithelium was delayed. The delay in fibroblast recruitment and wound contraction, the thinner scar tissue, and the increased survival of the bleb are all factors that suggest that beta irradiation may be a useful adjunct to glaucoma surgery. PMID- 2325996 TI - The nineties: a critical decade for medicine and mankind. PMID- 2325995 TI - Long-term comparative study of the Schocket and Joseph glaucoma tube shunts in monkeys. AB - Schocket and Joseph tube shunts were implanted in normal cynomolgus monkey eyes in order to compare the tissue response to the shunts as well as the pathways of aqueous flow associated with each. Following periods ranging from 5 to 10 months after implantation horseradish-peroxidase and/or fluorescein-labelled latex microspheres were inserted into the anterior chamber. The monkeys were then killed and the eyes studied by light, scanning, and transmission electron microscopy. In general, tissue responses to, and routes of aqueous flow associated with both shunts were similar: fibrous encapsulation of the drainage tubes and encircling bands, with aqueous flow through these fibrous capsules. PMID- 2325997 TI - Albedo concentration in the anterior eye: a phenomenon that locates some solar diseases. AB - I describe concentrations of reflected solar radiation (albedo) found at the usual sites of various conditions associated with exposure to the sun--pterygium, pinguecula, climatic droplet keratopathy and cataract and eyelid malignancy. Since the degree of limbal albedo concentration appears to be related to corneal curvature, patients at risk can be identified by a simple test and preventative measures taken. PMID- 2325998 TI - Combined penetrating keratoplasty and vitreoretinal surgery with the Eckardt temporary keratoprosthesis. AB - The Eckardt style temporary keratoprosthesis was used in six cases of five eyes undergoing simultaneous penetrating keratoplasty and pars plana vitrectomy. This device provided excellent visualization of posterior and peripheral intraocular structures and maintained a closed system during surgery. Corneal grafts remained clear in 80% of the cases, and macular attachment was achieved with either silicone oil or perfluoropropane gas in 50% of cases followed for at least 6 months. Visual function remained the same or improved in three eyes. Suggested refinements to the placement of this device include enlarging the trephination to 6.75 mm and the use of 8-0 nylon sutures to prevent cheesewiring of the soft silicone rim. A plano contact lens required during surgery to visualize the retina did not minify the image. Since the optical cylinder of the Eckardt temporary keratoprosthesis is shorter than that of a Landers-Foulks keratoprosthesis of similar diameter, it provides greater peripheral visualization. It is, however, less durable. PMID- 2325999 TI - Management of massive suprachoroidal hemorrhage. PMID- 2326000 TI - The importance of antiphospholipid antibodies. PMID- 2326001 TI - Diabetes 2000--closing the gap. PMID- 2326002 TI - Blood pressure and retinopathy in type I diabetes. AB - The relationship between blood pressure and diabetic retinopathy was evaluated in 249 young subjects with type I diabetes. Although hypertension is known to be associated with an increased risk for retinopathy, the effects of high-normal blood pressure are unknown. Retinopathy (158 of 249 subjects, 63%) is considerably more common in a young diabetic population than is hypertension (7 of 249 subjects, 2%). Thus, if blood pressure is important in the etiology or progression of diabetic retinopathy, levels below the hypertensive range (less than 141/90 mmHg) must be considered. The combined effect of hypertension and high-normal blood pressure (greater than 90th percentile but less than 141/90 mmHg) was studied. Elevation in diastolic blood pressure, alone, and in combination with elevated systolic blood pressure, correlated significantly (P less than 0.03) with retinopathy. The presence of high-normal blood pressure resulted in a prospectively higher occurrence of retinopathy and of progression of preexisting retinopathy. Glycohemoglobin (HbA1) and duration of diabetes also correlated with retinopathy. Both good glycemic control and maintenance of diastolic blood pressure below the 90th percentile for age may be important in relation to diabetic retinopathy. PMID- 2326003 TI - Macular blood flow response to acute reduction of plasma glucose in diabetic patients measured by the blue light entoptic technique. AB - The response of retinal blood flow to acute reduction in plasma glucose levels was studied in 20 poorly controlled type I diabetic patients. Perifoveal flow velocity was determined, using the blue-light entoptoscope, and arterial calibers measured, using a computer-aided digitizing system. Mean plasma glucose level was lowered from 17.7 +/- 4 to 7.0 +/- 1 mmol/l after a subcutaneous insulin infusion and measurements taken at both glucose levels. The autoregulatory change induced by breathing 60% oxygen at the two plasma glucose levels also was compared. Mean flow velocities were 0.54 +/- 0.28 mm/sec at a high plasma glucose level compared with 0.55 +/- 0.32 mm/sec at a low plasma glucose level, whereas hyperoxia reduced these by 16.58 and 16.71%, respectively. No significant difference in the responses of arterial diameters to hyperoxia between the two glucose levels was found. The authors conclude that acute reduction in plasma glucose level in this group of patients is not associated with significant changes in macular blood flow or in alteration in autoregulation. PMID- 2326004 TI - Optic disc size in central retinal vein occlusion. AB - Predisposing factors in central retinal vein occlusion (CRVO) have included various systemic disorders and glaucoma. Recent reports have suggested a possible relation between specific anatomic configurations of the optic nerve head and the development of anterior ischemic optic neuropathy. The authors analyzed several optic disc parameters in 57 ocular normotensive patients with unilateral CRVO and in 27 control subjects. There was no significant difference in the horizontal disc diameter and cup-to-disc ratio between eyes with unilateral CRVO, fellow eyes with CRVO, and control eyes. The current data suggest that there is no relation between optic disc size and CRVO. PMID- 2326005 TI - Quadrantic venous-stasis retinopathy secondary to an embolic branch retinal artery obstruction. AB - Venous-stasis retinopathy is a term used to describe the posterior segment findings of the ocular ischemic syndrome. These include midperipheral blot retinal hemorrhages, dilated retinal veins, attenuated arterioles, peripheral retinal microaneurysms, macular edema, as well as retinal and optic disc neovascularization. The authors recently evaluated a 71-year-old woman who presented with an asymptomatic calcific embolus in her right infero-temporal branch retinal artery. Classic venous-stasis retinopathy that was limited to the territory of the obstructed arteriole was present concurrently. This case appears to demonstrate that chronic retinal hypoperfusion and resultant venous-stasis retinopathy can be produced by not only high-grade, fixed stenosis but also by embolic disease. PMID- 2326006 TI - Surgical management of late-onset retinal detachments associated with regressed retinopathy of prematurity. AB - The authors report their experience in managing 16 cases of late-onset retinal detachments (RDs) associated with regressed retinopathy of prematurity (ROP). Fourteen (88%) of the 16 eyes were successfully reattached. An initial scleral buckling procedure was successful in 6 of 12 eyes. A pars plana vitrectomy was necessary in a total of eight eyes that either initially presented with proliferative vitreoretinopathy (1 case), posterior retinal breaks (1 case), subretinal fibrosis (1 case), vitreoretinal traction bands (1 case), or had persistent vitreoretinal traction after failed scleral buckling procedures (4 cases). Visual acuity stabilized or improved in 13 of the 14 eyes with successful retinal reattachment. Because these cases often have significant vitreoretinal traction and/or posterior retinal breaks, pars plana vitrectomy in conjunction with scleral buckling may be necessary in order to achieve long-term retinal reattachment. PMID- 2326007 TI - The effect of scleral buckling on ocular rigidity. AB - In a study of enucleated human eyes, the authors investigated the effect of scleral buckling on the ocular pressure-volume relationship. Intraocular pressure was recorded continuously during intravitreal infusion of saline solution before and after the application of encircling silicone elements. Scleral buckling produced a marked reduction in ocular rigidity, with reversibility of the effect on removal of the buckling elements. Similar results were obtained during incremental intravitreal air injection. The authors propose that the greater extensibility of silicone compared with sclera and the induced alterations in ocular shape are the primary factors responsible for the observed change in ocular rigidity. The clinical implications of these findings for intravitreal gas injection are discussed. PMID- 2326008 TI - The ocular manifestations of syphilis in the human immunodeficiency virus type 1 infected host. AB - Nine patients with active ocular or optic nerve involvement by syphilis who also had concurrent human immunodeficiency virus type-1 (HIV-1) infection are described. The ocular manifestations of syphilis led to the discovery of HIV-1 seropositivity in four of nine cases. Fifteen eyes were affected. Ocular manifestations were: iridocyclitis in three eyes, vitreitis in one eye, retinitis or neuroretinitis in five eyes, papillitis in two eyes, optic perineuritis in two eyes, and retrobulbar optic neuritis in two eyes. Three patients diagnosed with acquired immune deficiency syndrome (AIDS) had the worst initial visual acuities. Six of nine patients had evidence of concomitant central nervous syndrome (CNS) involvement with syphilis. Benzathine penicillin was administered intramuscularly to three patients. All three had relapses. Seven of nine patients treated intravenously with high-dose penicillin had dramatic responses to therapy with improvement in vision and serologies and no evidence of relapse. Regimens accepted for the treatment of neurosyphilis appear to be adequate for the treatment of ocular syphilis in HIV-1-infected patients though further long-term follow-up will be required. PMID- 2326009 TI - Endophthalmitis due to Blastomyces dermatitidis. Case report and review of the literature. AB - Blastomycosis very rarely affects ocular structures other than the eyelid. It is even more unusual for involvement to occur in the absence of active widespread disease. The authors report a 71-year-old woman with unresponsive endophthalmitis of the right eye who underwent enucleation. Results of microscopic examination of the globe showed severe acute and chronic granulomatous and nongranulomatous endophthalmitis as well as numerous fungi having the histologic features of Blastomyces dermatitidis. Although constitutional symptoms (weight loss, fatigue, night sweats) were noted by the patient, multiple investigations failed to disclose any evidence of systemic disease. PMID- 2326010 TI - Histoplasma capsulatum endophthalmitis after cataract extraction. AB - A 60-year-old white man from an area endemic for Histoplasma capsulatum presented with a vitreous wick, hypopyon iritis, and dense vitreitis 2 months after removal of an anterior chamber intraocular lens (IOL) for chronic iritis. A diagnostic vitrectomy was performed and H. capsulatum was cultured and identified 2 weeks later. Despite intravitreal and intravenous amphotericin as well as repeat vitrectomies, the inflammation worsened and the eye was removed. Results of histopathologic examination showed Histoplasma organisms along the vitreous wick, over the surface of the iris and ciliary body, and over the retina. No organisms were found in the choroid. Dalen-Fuchs-type nodules similar to those of sarcoid also were noted, but there was no evidence of granulomatous inflammation in the uvea. Because of his unilateral disease with Histoplasma in the vitreous wick, negative serology, and an absence of systemic infection, the authors believe that this patient had a previously unreported form of ocular Histoplasma, exogenous postoperative Histoplasma endophthalmitis. PMID- 2326011 TI - Histopathologic verification of Verhoeff's 1918 irradiation cure of retinoblastoma. AB - The authors studied an eye obtained postmortem from the first patient with a successfully irradiated retinoblastoma. This patient, first treated by Verhoeff in 1917, had been followed for 71 years. Ophthalmoscopy disclosed a depressed chorioretinal scar, approximately 3 disc diameters (DD) in size, with baring of the sclera temporal to the macula. This case is historically significant, in that Verhoeff and Reese debated as to whether this tumor regressed spontaneously or secondary to irradiation. Results of histopathologic, immunohistochemical, and ultrastructural examination showed a chorioretinal, neuroglial scar without evidence of calcification, necrotic tumor cells, or residual retinoblastoma. The authors discuss the clinical and histopathologic findings in spontaneously regressed retinoblastoma, retinoma/retinocytoma, and irradiated retinoblastoma. They believe that Verhoeff was correct in his belief that x-ray therapy had cured this patient. PMID- 2326012 TI - Malignant melanoma associated with melanocytoma of the optic disc. AB - A 61-year-old white man underwent enucleation because of progressive growth of a pigmented epipapillary tumor that was diagnosed 9 years earlier as an optic nerve and juxtapapillary melanocytoma. Histopathologic studies showed the tumor was a malignant melanoma of the optic disc and juxtapapillary retina and choroid. Foci of typical melanocytoma cells were within the tumor. The tumor produced segmental atrophy of the optic nerve. This is a rare example of a malignant melanoma developing in conjunction with a lesion that possessed typical clinical and histopathologic features of a melanocytoma of the optic disc. PMID- 2326013 TI - Determinants of hospital charges and length of stay for ocular trauma. AB - Ocular trauma is an important cause of blindness and visual impairment in the United States. This study examined the economic effect of ocular trauma by evaluating hospital length of stay and charges for 4406 discharges from Maryland hospitals from 1979 to 1986. Length of stay declined on average 6.1% per year during this period. Length of stay was positively associated with age which could not be accounted for by the severity of the trauma or the presence of secondary trauma diagnoses. Other factors associated with length of stay included race, principal diagnosis, secondary trauma, and characteristics of the hospital. National projections estimate greater than 227,000 hospital days and $175 to $200 million in hospital charges alone are due to ocular injuries every year. PMID- 2326014 TI - The effect of intraocular gas and fluid volumes on intraocular pressure. AB - Large increases in the intraocular pressure (IOP) of postoperative gas-containing eyes may require the removal of gas or fluid to reduce the IOP to the normal range. Application of the ideal gas law to Friedenwald's equation provides a mathematical model of the relationship between IOP, intraocular gas and fluid volumes, and the coefficient of scleral rigidity. This mathematic model shows that removal of a given volume of gas or fluid produces an identical decrease in IOP and that the more gas an eye contains, the greater the volume reduction necessary to reduce the pressure. Application of the model shows that the effective coefficient of scleral rigidity is low (mean K, 0.0021) in eyes with elevated IOP that have undergone vitrectomy and retinal cryopexy and very low (mean K, 0.0013) in eyes with elevated IOP that have undergone placement of a scleral buckle and band. By using the appropriate mean coefficient of rigidity, the volume of material to be aspirated to produce a given decrease in IOP can be predicted with clinically useful accuracy. PMID- 2326015 TI - Subsurface ultrasound microscopic imaging of the intact eye. AB - The authors have developed a method of obtaining images of cross sections of the intact eye at microscopic resolution. High-frequency ultrasound transducers (100 MHz) have been developed and incorporated into imaging devices. These devices are capable of producing images to a depth of 4 mm at an axial and lateral resolution approaching 20 microns. Resolution exceeds that of current combined A- and B-scan imaging devices by a factor of approximately 10. Microscopic images of ocular structures including Schlemm's canal, cornea, iris, ciliary muscles, and retina have been produced in eye bank eyes. These studies show the feasibility of developing an apparatus to be used in the clinical setting for examining anterior structures of the eye not visible by current techniques. PMID- 2326016 TI - Preretinal membranes. PMID- 2326017 TI - Alzheimer's disease and vision: correlation versus causation, revisited. PMID- 2326018 TI - Glaucoma suspect treatment trial. PMID- 2326019 TI - Penetrating keratoplasty for pseudophakic bullous keratopathy associated with closed-loop anterior chamber intraocular lenses. AB - Closed-loop anterior chamber intraocular lenses (AC IOLs) are associated with a high incidence of pseudophakic bullous keratopathy (PBK). The prognosis for recovery of vision with penetrating keratoplasty and the exchange of one type of AC IOL for another remains controversial. A total of 40 consecutive patients with closed-loop AC IOLs and varying degrees of PBK underwent penetrating keratoplasty, explanation of the closed-loop AC IOL, and implantation of a flexible tripod AC IOL--all done with a uniform technique. The average follow-up study was 24 months. Average preoperative visual acuity was 20/170 (range, 20/25 hand motions) and average postoperative visual acuity was 20/44 (range, 20/20-no light perception). A total of 23 eyes (57.5%) achieved a visual acuity of 20/40 or better. Eleven eyes (27.5%) had a visual acuity of 20/200 or worse. Persistent cystoid macular edema was the most frequent cause of poor vision postoperatively (4 eyes), followed by age-related macular degeneration (3 eyes) and graft rejection (2 eyes). This is the first series documenting a good visual outcome for at least 2 years after penetrating keratoplasty and exchange of a closed-loop AC IOL for a single type of flexible tripod AC IOL. PMID- 2326020 TI - Peripheral anterior synechia overlying the haptics of posterior chamber lenses. Occurrence and natural history. AB - Sixty consecutive eyes that met the standard criteria for cataract surgery underwent phacoemulsification with insertion of a posterior chamber lens implant. The filtration angle of each eye was examined with routine postoperative gonioscopy in a prospective manner. Peripheral anterior synechia (PAS) overlying the position of the lens haptic (lens haptic PAS) were observed in up to 80% of eyes implanted with haptics vaulted anteriorly by 10 degrees. The rate of occurrence of lens haptic PAS was reduced by a statistically significant level in a group of eyes implanted with nonvaulted haptics. Most of the lens haptic PAS were observed early in the postoperative period and remained stable in size. Progression in size was noted quantitatively in three eyes and documented with goniophotography in two eyes. A delay in the presentation of lens haptic PAS was observed in seven eyes. A postoperative increase in intraocular pressure (IOP) associated with enlargement of lens haptic PAS developed in one patient with preoperative chronic open-angle glaucoma. These observations support others that progressive PAS overlying posterior chamber lens haptics can be a form of progressive angle-closure glaucoma in pseudophakia. This mechanism may be more likely to occur in eyes implanted with anterior vaulted haptics. PMID- 2326021 TI - Management of cornea-lens touch after filtering surgery for glaucoma. AB - The success of filtering surgery for glaucoma may be compromised by a postoperative flat anterior chamber associated with cornea-lens touch, hypotony, and absence of wound leakage. The clinical course of eight patients with this complication was reviewed. Six patients had chronic angle-closure glaucoma. Only one patient responded to medical therapy which included frequent topical application of atropine sulfate 3.0% for 1 hour. Reformation of the anterior chamber with air and drainage of any suprachoroidal fluid was immediately performed in the remaining seven. At the time of follow-up (mean, 16 months), the glaucoma was controlled in all eyes except one. The mean intraocular pressure (IOP) was 14 mmHg in those eyes not requiring reoperation. Six (75%) of eight eyes had diffuse, succulent filter blebs. Five eyes (63%) required no antiglaucoma medications, one eye (12%) required one, one eye (12%) required two, and one eye (12%) underwent repeat filtering surgery. The results suggest that, once medical therapy is not immediately successful, prompt surgical reformation of the anterior chamber along with drainage of any suprachoroidal fluid may preserve the filter blebs in these eyes. PMID- 2326022 TI - The long-term outcome of patients undergoing iridocyclectomy. AB - The authors evaluated the long-term results of iridocyclectomy to remove a lesion of the iris or ciliary body in 52 patients. The mean follow-up time was 8.5 years. The excised lesions were benign in 53% of the cases, spindle cell-type melanomas in 19% of the cases, mixed cell- or epithelioid cell-type melanomas in 25%, and an adenocarcinoma of ciliary epithelium in 2%. Visual outcome was generally good, with 43% of the patients achieving visual acuity of 6/7.5 or better and 57% achieving 6/15 or better. In 29% of the patients, enucleation was finally required, and in 10% of the patients there was metastasis of the melanoma. In 11 of the 15 patients who had a subsequent enucleation, the tumor was a melanoma of mixed cell or epithelioid cell type, and in 12 of these 15 patients the surgical margin was involved by the tumor in the iridocyclectomy specimen. All five patients with metastatic disease had melanomas of mixed cell or epithelioid cell type with involvement of the surgical margin in the iridocyclectomy specimen. PMID- 2326023 TI - A primate model of anterior segment ischemia after strabismus surgery. The role of the conjunctival circulation. AB - Fornix conjunctival incisions in strabismus surgery may provide partial protection against anterior segment ischemia by preserving the perilimbal conjunctival-Tenon's circulation, which is disrupted with limbal conjunctival incisions. Six adult cynomolgus monkeys underwent tenotomies of three or four rectus muscles by making limbal conjunctival incisions in one eye and fornix incisions in the other. Iris fluorescein angiography and slit-lamp biomicroscopy were used to monitor changes. The eyes that had limbal incisions exhibited more severe anterior segment ischemic changes than the eyes that had fornix incisions in every instance of four rectus muscle surgery. PMID- 2326024 TI - Subluxated (ectopic) lenses in adults. Long-term results of pars plana lensectomy vitrectomy by ultrasonic fragmentation with and without a phacoprosthesis. AB - The long-term results of pars plana lensectomy-vitrectomy by ultrasonic fragmentation for 18 consecutive subluxated (ectopic) lenses were retrospectively reviewed. There were no serious operative or postoperative complications at the 16-year follow-up. Visual acuity of 20/15 to 20/50 was obtained in 16 (89%) of 18 eyes. Lensectomy-vitrectomy for subluxated lenses appears to be a relatively safe and effective procedure. The technique can be combined with a phacoprosthesis (intraocular lens implant) in adults. PMID- 2326025 TI - Vitrectomy for epiretinal membrane with Candida chorioretinitis. AB - Four eyes underwent vitrectomy and epiretinal membrane dissection for tractional retinal detachment (RD) or macular pucker associated with Candida chorioretinitis. The epiretinal membranes were vascularized and, in three of four eyes, were associated with full-thickness retinal scars, presumably at the site of previous active Candida chorioretinitis. The epiretinal membranes were successfully removed in all four cases. Visual results depended on the degree of macular pathology and the presence and location of a full-thickness retinal scar. PMID- 2326026 TI - Pars plana vitrectomy in the management of retinal detachments associated with degenerative retinoschisis. AB - Pars plana vitrectomy and gas-fluid exchange were used to successfully reattach eyes of 12 patients who had symptomatic retinoschisis retinal detachments (RDs) associated with large or posterior outer-layer holes. Visual acuity improved postoperatively in seven (58%) eyes, was unchanged in two (17%) eyes, and decreased in three (25%) eyes. Loss of vision was secondary to a mild posterior subcapsular cataract in one eye and to epiretinal membranes in the other two. In two other eyes, cataracts developed that subsequently required an extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (PC IOL) implantation with 20/20 visual acuity in both eyes after cataract surgery. All eyes with a macula-involved RD stabilized or improved in visual acuity. Surgical indications, techniques, and results in the management of these retinoschisis RDs are discussed. PMID- 2326027 TI - Visual field defects in patients with insulin-dependent and noninsulin-dependent diabetes. AB - Automated perimetry (Humphrey 30-2) was used to quantitate visual field sensitivity in diabetic patients with either little or no retinopathy (n = 38) or mild background diabetic retinopathy (n = 19) and in visually normal controls (n = 40). Foveal thresholds were unaffected in the diabetic patients but significant reductions in visual field sensitivity, measured by both the mean deviation and the pattern standard deviation indices of visual field sensitivity, were observed in the diabetic patients. Subgroup analyses showed that this sensitivity reduction primarily occurred in noninsulin-dependent diabetic patients. Among the diabetic patients, 26.3% of the visual fields were flagged as "probably abnormal." This percentage was greatest among the noninsulin-dependent patients with mild background diabetic retinopathy (72.3%). The sensitivity reductions observed in the noninsulin-dependent patients with mild background diabetic retinopathy tended to be localized in the superior quadrants and correlated with the extent of retinal vascular compromise evident from vitreous fluorophotometry (r = 0.603). These findings imply that in diabetic patients visual field defects (1) often can be detected in patients with at most moderate retinopathy, (2) occur more frequently in noninsulin-dependent patients than in insulin-dependent patients, and (3) may result from subclinical microangiopathy. PMID- 2326028 TI - Progression of diabetic retinopathy after pancreas transplantation. The University of Michigan Pancreas Transplant Evaluation Committee. AB - The progression of diabetic retinopathy after combined pancreatic and kidney transplantation was studied in eight patients for 12 to 49 months. Four patients who had rapid pancreatic graft failure constituted a control group for comparison with four patients who retained functioning grafts. Using Fisher's exact probability test, the authors found no posttransplantation difference between the two groups in visual acuity lost, severity of diabetic macular edema, extent of capillary closure, progression of preretinal gliosis, development of disc or preretinal neovascularization, or worsening of the severity of the retinopathy. Achievement of normoglycemia by pancreatic transplantation is not effective in halting the progression of diabetic retinopathy in patients who already have severe diabetic microangiopathy joined the current follow-up. PMID- 2326029 TI - The pigtail probe, revisited. AB - Choosing a method for repair of a canalicular laceration can be a challenge for the ophthalmic surgeon. Important principles to consider include direct anastomosis of the severed canalicular ends, endocanalicular support, and avoiding trauma to the uninvolved portions of the nasolacrimal system. The round tipped, eyed pigtail probe has been found to be a safe, effective instrument in identifying and repairing a canalicular laceration. The authors also found it helpful in reconstructing partially excised canaliculi after tumor removal with Mohs' surgery. A high degree of anatomic and functional success was achieved using this instrument in a careful and meticulous technique. PMID- 2326030 TI - Bilateral orbital involvement in fatal giant cell polymyositis. AB - The case of a young woman with giant cell polymyositis is described. She had bilateral, severe, midly painful proptosis and ophthalmoplegia. Extensive pharyngeal, laryngeal, and cardiac muscle involvement occurred 18 months later coincident with fatal cardiac arrhythmia. At autopsy, extensive muscle necrosis and giant cells were noted in extraocular, pharyngeal, laryngeal, and cardiac muscle with only minimal involvement of other striated muscles. PMID- 2326031 TI - Lacrimal gland ductule stones. AB - Chronic unilateral conjunctivitis may be caused by various infectious, inflammatory, neoplastic, or mechanical conditions. Two patients with persistent unilateral conjunctivitis were cured after removal of dacryoliths from the palpebral lobe of the ipsilateral lacrimal gland. Although lacrimal gland ductular dacryoliths are rare, this entity should be included in the differential diagnosis of chronic unilateral conjunctivitis. PMID- 2326033 TI - Simultaneous maxillary and mandibular orthognathic surgery stabilized by rigid internal fixation. AB - Rigid internal fixation was used successfully in 111 consecutive cases in which both the maxilla and the mandible were mobilized simultaneously. The use of rigid fixation allowed for early mobilization of the mandible, which facilitated resumption of orthodontic therapy after surgery. The favorable short-term results achieved indicate the need to study the long-term stability of the technique. PMID- 2326032 TI - Use of low-dose ketamine hydrochloride in outpatient oral surgery. AB - This study compares the quality of anesthesia achieved with low-dose ketamine with that of methohexital sodium. In a double-blind study of 40 healthy adult patients undergoing a variety of minor oral surgical procedures, the anesthetic techniques were assessed with respect to the following parameters: patients' subjective evaluation of the anesthesia, the level of response to injection of local anesthetic, psychomotor ability after surgery, recovery times, and the frequency of adverse effects. From these observations, it was deduced that when low-dose ketamine was used with diazepam, meperidine, and nitrous oxide, it proved to be a safe and effective supplement for minimizing pain, discomfort, and anxiety before injection of local anesthetic. Patients' appreciation of the level of anesthetic achieved, psychomotor ability, adverse reactions, and recovery time was not significantly different from the methohexital sodium group. PMID- 2326034 TI - Dental implications in Ehlers-Danlos syndrome. A case report. AB - Ehlers-Danlos syndrome is an unusual disease entity afflicting many body systems. Temporomandibular joint dysfunction has been described in an isolated number of cases. Ensuing complications should be recognized and the treatment plan modified accordingly. The following is a case report and review of the literature. PMID- 2326035 TI - An animal model for mucositis induced by cancer chemotherapy. AB - Mucositis induced by chemotherapy is a painful and often dose-limiting side effect of cancer therapy. Furthermore, loss of the integrity of the oral epithelium often provides a microbial portal of entry and leads to sepsis. The present study describes the first animal model for chemotherapy-induced mucositis. The combination of three intraperitoneal injections of 5-fluorouracil at 5-day intervals and superficial mechanical mucosal irritation resulted in clinical breakdown of the oral mucosa characterized by ulcerative mucositis in Golden Syrian hamsters. Both clinical and histologic evaluation demonstrated that these changes were similar to those described in human beings and followed a pattern influenced by the degree of myelosuppression. This model should be of significance in establishing the stomatotoxicity of new chemotherapeutic agents, in evaluating medicaments to treat mucositis, and in studying the influence of oral mucosal breakdown on sepsis in myelosuppressed persons. PMID- 2326036 TI - Chlorhexidine inactivation by saliva. AB - Chlorhexidine mouth rinsing is commonly used for oral flora reduction. Indigenous microorganisms (viridans streptococci) are significantly suppressed, while "hospital-acquired" gram-negative bacilli are not affected in vivo. To explain the discrepancies between good in vitro and poor in vivo activity of chlorhexidine, minimum bactericidal concentration values for 120 isolates were studied by means of a standard dilution method in fresh whole saliva, broth, and glucose 5%. Both saliva and broth significantly reduced the bactericidal activity of chlorhexidine against all microorganisms tested as compared to glucose 5% (p less than 0.01). Minimum bactericidal concentrations for indigenous flora were significantly lower than the values obtained for the "hospital-acquired" microorganisms (p less than 0.05). These observations of chlorhexidine inactivation by saliva may explain why chlorhexidine mouth rinsing is of limited value in decontaminating the oral cavity. PMID- 2326037 TI - Patient perception of cross-infection prevention in dentistry. AB - A questionnaire survey was conducted among 301 dental hospital and general practice patients in the Glasgow region to assess their perception and awareness of cross-infection preventive methods used in dentistry. Sixty percent of the respondents were aware that dentists have been advised to wear gloves routinely, and a large majority thought that the gloves were for the dentists' own protection. Almost all the respondents did not mind the dentist wearing either gloves or masks during treatment. One third of the total population were ignorant about sterilization methods used in dentistry. One half of the hospital patients and one third of the general practice patients thought that infectious diseases could be contracted via the dentist or his instruments. Although two in three of the respondents surmised that transmission of AIDS in the dental clinic is unlikely, one half of the general practice patients were unwilling to visit the dentist if the latter was known to treat patients with AIDS. This survey indicates that there is a great deal of confusion and fear among the public on cross-infection in the dental clinic, which needs to be rectified by a properly targeted health education campaign. PMID- 2326038 TI - Basal cell adenocarcinomas of the major salivary glands. AB - Basal cell adenoma of salivary gland has become an established variant of monomorphic adenoma since its segregation from pleomorphic adenoma in 1967. Although there have been many comprehensive reports about benign basal cell adenomas, only rare case reports of malignant basal cell type neoplasms have appeared in the literature. Described in this report are the clinicopathologic features of 29 cases labeled basal cell adenocarcinomas that had morphologic characteristics of basal cell adenomas but infiltrative, perineural, and intravascular growth features that indicated a malignant potential. With limited follow-up, seven tumors are known to have recurred, and three of these metastasized to lymph nodes and lung. One patient died with extensive local spread of the tumor. All patients were adults. The peak incidence was in the sixth decade of life, and there was no gender predilection. The parotid gland was the predominant site. A solid type growth configuration was most frequent; membranous, trabecular, and tubular types were less frequent, in that order. Three patients also had dermal cylindromas, perhaps indicative of a salivary gland-skin adnexal diathesis that has been previously reported. PMID- 2326039 TI - Scanning electron microscope study on the action of endodontic irrigants on bacteria invading the dentinal tubules. AB - Three groups of 10 maxillary anterior teeth each, which had been exposed to oral media, were flushed with 9 ml of tap water, physiologic saline solution, and alternating irrigation with NaOCl and hydrogen peroxide respectively. Residual caries, necrotic tissue remnants, intertubular cavitation, and dentinal tubule invasion by bacteria were searched for by means of the scanning electron microscope. Cuboidal sodium chloride crystals were very frequently found deposited in the main root canal, in lateral canals, and inside the dentinal tubules. This study discusses the important role NaOCl may play as a solvent of dental plaque and necrotic tissue remnants in the clinical endodontic treatment of infected teeth that had been exposed to oral media. PMID- 2326040 TI - Prediction of efficacy of bitewing radiographs for caries detection. AB - Although bitewing (BW) radiographs play an indispensable role in the detection of interproximal caries, it is not always clear when they should be made. The present study was designed to test the hypothesis that a person's caries and restorative history may be predictive of his or her caries future. Full-mouth radiographic examinations (FMX) and subsequent BW radiographs from 349 adults (age 20 or more) selected at random were examined. Possible risk factors for caries recorded for each patient included the number and type of carious lesions and the restorative experience of the patient. Linear logistic regression models were evaluated to estimate the efficacy of the possible risk factors as predictors of the presence of caries on the BW radiographs. Of the 349 adults examined, 91 (26%) had one or more new carious lesions at the time of their BW examination. The probability of caries in this population at the time of the BW examination increases both with lengthening interval between the FMX and the BW radiographs and with the number of restorations at the time of FMX. A regression model was adopted that estimates the probability of caries being detected on BW radiographs. We found that to provide the most good for the most patients (minimize cost), the threshold level for ordering follow-up radiographs should be when the probability of detecting caries is 5%. It may be seen that even when a person has no caries or restorations at the time of the FMX there will be a 5% chance that BW radiographs will reveal the presence of caries 1.5 years later. The 5% threshold is reached sooner in the presence of caries or restorations. PMID- 2326041 TI - Temporomandibular joint: variation of normal arthrographic anatomy. AB - The arthrograms of 34 individuals with asymptomatic, clinically and arthrographically normal temporomandibular joints were analyzed. The results showed a substantial variation of the dimensions and configuration of the joint compartments. Thus the anterior recess of the lower joint compartment was small in 15 joints (44%), medium-size in 16 joints (47%), and large in three joints (9%). The upper margin of this recess was flat or convex in 24 joints (71%) and concave in 10 joints (29%). These observations contradict previous assumptions about a strict association between the configuration and dimension of the anterior recess of the lower joint compartment and the position of the disk. It was concluded that dimension and configuration of the joint compartments should not be used as the only criteria for diagnosis of the position of the disk. PMID- 2326042 TI - How invasive is TMJ double-contrast arthrography in combination with cinematography? Patient discomfort versus known diagnostic gain. AB - There is no doubt that double-contrast TMJ fluoroscopic tomography enables a differential diagnosis and treatment in internal derangement pathosis. Its indication is, apart from the expected diagnostic gain, also determined by the degree of its invasiveness, and other alternative diagnostics being available (nuclear magnetic resonance). Data on patient discomfort and complications were gathered in 63 arthrotomographies; pain sensations and mandibular mobility, during and after the procedure in particular, were studied. We consider, along with Westesson, the procedure to be less invasive than commonly considered, once the surgeon-radiologist has gained enough experience. PMID- 2326043 TI - Calcification of the stylohyoid ligament: incidence and morphoquantitative evaluations. AB - To study the incidence of calcification of the stylohyoid ligament, 286 orthopantomographs were analyzed. All patients had no symptoms. The total incidence of calcification was noted to be high, at 84.4%. The number and the length of calcifications increased with age, and there was no relationship to sex or mandibular size. The phenomenon is often evident bilaterally. The variety of results reported in the references depends on different criteria in radiographic evaluation and in patient selection. PMID- 2326044 TI - Vascular events in experimental otitis media models: a comparative study. AB - The vascular leakage and components of middle ear effusion (MEE) were determined and compared in various experimental otitis media models in the rat: purulent otitis media (POM); serous otitis media (SOM); mucoid-like otitis media (MOM); stimulating the external auditory canal with a 14 degrees C airstream and vagotomy. When the Evans blue technique was used, all otitis media models exhibited a significant increase in middle ear vessel permeability. The MEEs contained numerous PMNLs, except for animals stimulated with a 14 degrees C airstream, in which the MEE was free of cells. The IgG/SIgA ratio in MEEs indicated that the MEE components are derived from serum in the early phases of fluid accumulation, in these otitis media models. In POM, MEE components appeared to be derived from local synthesis by the middle ear mucosa as well. PMID- 2326045 TI - Influence of membrane surface potential and of net charge on aminoglycoside binding to the organ of Corti of guinea pigs. AB - Gentamicin binding to homogenates of the organ of Corti of guinea pigs was investigated by altering the magnitude of the membrane surface potential and by testing the potencies of various polyamines and polyamino acids with different numbers of amino groups and different net charge to inhibit or displace bound gentamicin. Diminishing or increasing the ionic strength of the milieu resulted in an increase and a decrease in drug binding, respectively. This observation may be accounted for by the negativity of the membrane surface potential which was enhanced or reduced, when the concentration of cations in the milieu was decreased or increased, respectively. Polyamines and polyamino acids displaced bound gentamicin and inhibited gentamicin binding as a function of the number of amino groups present within the molecule and of their cationic nature. These results point out the importance of considering the surface potential of biological membranes and the net positive charge of the drug in estimating its affinity for the binding site. PMID- 2326046 TI - Hemangiopericytoma as the cause of Collet-Sicard syndrome. AB - Collet-Sicard syndrome is one of the jugular foramen syndromes in which the last four cranial nerves are involved whereas the sympathetic plexus is spared. It is very uncommon to find facial paralysis associated to this syndrome and most interestingly, a hemangiopericytoma at this location to cause all these paralyses. We have not been able to find a similar case in the literature, and thus present our case. PMID- 2326047 TI - Blink reflex: prognostic value in acute peripheral facial palsy. AB - The blink reflex (BR) has been studied during the first 2 weeks in 122 patients with Bell's palsy and Ramsay Hunt's syndrome. According to early BR (R1), the patients were divided into 3 groups: R1 less than or equal to 13 ms (16 cases); R1 greater than 13 ms (54 cases), and absent BR (52 cases). There was a remarkable tendency towards a satisfactory recovery from paralysis if BR occurred during the first 2 weeks from onset (p less than 0.001). In patients with normal BR, 93.7% had a satisfactory recovery, and in patients with delayed R1, the prognosis was still good: 86.8% had a satisfactory recovery. When the reflex was absent a bad prognosis was given in 55.8% of the patients. The BR and the severity of the lesions according to electroneurograms was tested in 111 patients and found to be significantly correlated (p less than 0.001). BR seems to be a useful index for predicting the prognosis in an early stage of the paralysis, however, more than one test should be performed at the same time to accurately establish the prognosis. PMID- 2326049 TI - Operative management of children's fractures. PMID- 2326048 TI - Sealing of the round window reversibly affects auditory brainstem response latencies. AB - The round window (RW) niche was sealed in 12 adult female albino Sprague-Dawley rats. Electrophysiological auditory function was measured with a computerized auditory brainstem response (ABR) recording technique, using 1- and 6 kHz stimuli. ABR measurements were performed prior to closure of the niche, immediately after the sealing, and 4 h, 24 h and 7 days later. After sealing, the latencies elicited by a 6 kHz stimulus increased, but returned to normal between 24 h and 7 days after closure. Stimulation with 1 kHz did not influence the latencies in such a clear-cut manner as when using 6 kHz. It is conceivable that sealing of the RW deprives a minor fraction of oxygen supplied to the basal part of the cochlea through the RW membrane, a procedure which by us is monitored as transient electrophysiological changes. PMID- 2326050 TI - Operative management of fractures of the shaft of the radius and ulna. AB - Diaphyseal fractures of the radius and ulna usually can be managed by closed reduction and immobilization in a long arm cast. Open fractures may benefit from pinning if the reduction will be difficult to maintain. Fractures that cannot be reduced or for which satisfactory alignment maintained are best managed operatively. Our preference is for intramedullary fixation. Operative management will be necessary most frequently in children older than age 10. PMID- 2326051 TI - The problem of Monteggia fracture-dislocations in children. AB - When a Monteggia fracture is recognized and treated immediately, the results are excellent. Poor results are mostly caused by initially missing the diagnosis. Operative intervention is usually required for those fractures that are unstable after manipulation or recognized too late after injury. PMID- 2326052 TI - Fractures of the olecranon and radial neck in children. AB - Over one half of radial neck fractures are associated with other injuries about the elbow. Most radial neck fractures can be treated with closed reduction or with percutaneous probing, even if the other associated injuries require open reduction. The results are good, although radiologic imperfections may be seen after healing. In the older child, olecranon fractures that have significant displacement usually require open reduction with internal fixation. PMID- 2326053 TI - Residuals of elbow trauma in children. AB - Residuals of trauma involving the distal humerus in children are mostly the result of delayed treatment or incomplete reduction of the fracture fragments. Cubitus varus after supracondylar fractures is primarily a cosmetic problem. Correction of this deformity is possible surgically but requires strict attention to detail because a high incidence of complications are associated with performance of a supracondylar osteotomy. Cubitus valgus, on the other hand, does have some functional problems. Thus, there is more of a functional reason to correct cubitus valgus deformities. The biologic complications of lateral condyle fractures such as lateral spur formation and the mild cubitus varus that occurs usually do not require surgical intervention. Those problems associated with techniques of treatment, such as a delayed open reduction, non-union, and angulation, again can be remedied surgically. Specific basic principles, as outlined in this article, however, must be followed to achieve success. PMID- 2326054 TI - Internal fixation of children's fractures of the lower extremity. AB - Lower grade fractures are by definition stable and almost always treated with casting or functional splinting. The best kind of fixation for the higher grade fractures, however, differs between adults and children. Appropriate treatments are discussed, and case-study illustrations are provided. Background on the anatomy of the tibia and femur is included. PMID- 2326055 TI - External fixation in multiply injured children. AB - External fixation treatment for selected fractures can be as readily applied to children as to adults, although only a small percentage of pediatric fractures require this method. The best situations for the use of external fixation in children are in cases of multiple organ system injuries and in fractures associated with skin loss or large wounds. In these situations, while the child's other problems are being treated, external fixation provides excellent temporary stabilization to facilitate fracture management. PMID- 2326056 TI - [Polymerase chain reaction in clinical diagnosis]. AB - The polymerase chain reaction (PCR) is a novel method that amplifies selective sequences of DNA or RNA molecules with unparalleled efficiency. The specificity of PCR amplification is based on two oligonucleotide primers which flank the DNA fragment to be multiplied and hybridize to opposite strands. Repeated cycles of thermal denaturation, primer annealing, and enzymatic extension by the heatstable Taq DNA polymerase result in exponential augmentation of the target DNA. PCR is simple, rapid, and highly sensitive. The nucleic acid content of a single cell is sufficient to detect a particular sequence. This method has an enormous impact on the detection of genetic mutations, sequence polymorphisms and infective agents. This review depicts the mechanism of PCR and explores its applications in clinical diagnostics. PMID- 2326057 TI - [Hematologic changes in sarcoidosis]. AB - On the basis of the literature authors analyse the importance of the involvement of spleen in sarcoidosis and the haematological changes that follow from this. In a group of patients with sarcoidosis of their own department (more than 1200 patients) they observed 2 women with thrombocytopenic purpura, one woman with thrombo- and leukocytopenia, and one woman with agranulocytosis. They shortly reviewed the previous history of their patients, the disease process, and the results of the treatment. All the four of their patients were given corticosteroid treatment and with this the thrombocytopenia was cured. No relapse was observed. One of the patients they have followed for 25 years, and an other one for 20 years. The patient with agranulocytosis was given corticosteroid, granulocyte concentrate, gammaglobulin, and antibiotics, too. Her status also became settled, and during the 10 years after her first observation we did not notice any relapse. The fourth patient is still being treated. PMID- 2326058 TI - [Doubts about the management of acute otogenic meningitis in infants and children]. AB - The authors present the cases of children suffering from acute otitic meningitis in respect of the applied therapy. On the basis of the courses and the dates of the literature the authors recommend the operation only after the unsuccessful antibiotic therapy. They draw attention to the importance of avoiding the growth of the brain pressure appearing during the operation performed in narcosis and to the importance of cooperating among specialists. PMID- 2326059 TI - [Tomato skin in the common bile duct after endoscopic sphincterotomy]. AB - Lithotomy and endoscopic sphincterotomy were carried out in a 83-year-old woman because of choledocholithiasis. One year later calculi and tomato skins were found in the common bile duct. Significance is attributed to the tomato skins in the development of calculi. The attention is drawn to the observation that operative interventions performed through the Vater's papilla, spontaneous or iatrogenic choledochoduodenal fistulas create favourable conditions for foreign material to get into the choledochus and this may cause lithogenesis. PMID- 2326060 TI - [Double kidney and ureterocele associated with kidney calculi]. AB - The simultaneous occurrence of infrequent alterations--double kidney, ureterocele and calculi--is reported. Following the operation performed in 2 steps the patient became free of complaints and according to the repeated controls the dilatation of the efferent system regressed, no reflux was observed. PMID- 2326061 TI - [Clinical evaluation of hairy cell leukemia]. PMID- 2326062 TI - [Additional data on the article "Ectrodactylia, ectodermal dysplasia, cleft lip and palate syndrome", by G. Ostorharics-H. and Ildiko Lazar]. PMID- 2326064 TI - [Preparation of human heart valve grafts in Hungary]. AB - A method of preparation and preservation of valved aortic and pulmonary allografts is described, used in corrective procedures of congenital heart diseases. The method of sterilization, exclusion of bacterial and viral contaminations is enhanced. Complications did not occur after implantations of the grafts. PMID- 2326063 TI - [Fatal thrombotic microangiopathy in the mother and fetus]. AB - The appearance of thrombotic microangiopathy (thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome) could have been documented in a 23 years old pregnant woman, who had been treated previously for immune-thrombocytolytic purpura. The disturbing anamnestic data caused significant delay in correct diagnosis and in starting of fresh-frozen plasma therapy, so the woman and her fetus (in utero) had been died. The specific histological microangiopathic lesions could have been well documented by the autopsy of the mother, however no such alterations could have been detected in the fetus and placenta. This latter intriguing observation might be remarkable in the evaluation of several concepts dealing with the aetiopathogenesis of thrombotic microangiopathy. The short review of literature of thrombotic microangiopathy in pregnancy and puerperial period is also given. PMID- 2326065 TI - [A computerized follow up system of obstetric and genetic care]. AB - The authors have implemented and introduced a new filing system representing the complexity of obstetric, genetic and neonatal care for the three counties of the Eastern part of Hungary. Data about the pre-, peri- and postnatal management are supplied by the genetic/teratologic, obstetric, neonatal and pathological units and processed at the Department of Obstetrics and Gynaecology, University Medical School of Debrecen with an IBM compatible AT computer. This computerised registry is based on the personal identification number, so it is easy to handle for storing data about the course and outcome of a large number of pregnancies as well as the detection and follow-up of fetal malformations and genetic diseases. The computer register is suitable for easy and systematic storage of the more than 20 thousand pregnancies screened by both maternal serum AFP and ultrasound including nearly 500 prenatal diagnosis cases per year. When devising the system, the classic parameters of the "revised Tauffer statistics" have been taken into consideration, but the emphasis has been put mostly on the assessment of fetal/infantile health status and the prevention of malformations and genetic diseases. This computerised system greatly facilitates the correct assessment of statistical parameters in related medical fields and provides better possibilities for studying the cause and effect relationship between the efficacy of medical care and perinatal events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326066 TI - [Gallbladder torsion in infants]. AB - The infrequent case of gallbladder torsion and accompanying Meckel's diverticulum in a 3-year-old girl, is described. Detorquation, cholecystectomy and resection of the diverticulum were performed. Condition of the development of the disease as well as its clinical aspects and therapy are discussed. It is suggested to explore the abdominal cavity for other developmental anomalies in the course of the operation. The patient recovered without complications and left the hospital 14 days after the operation. PMID- 2326067 TI - [Correlation of the length of the preoperative period and the severity of appendicitis]. AB - 1364 appendectomy were performed by the authors in two hospitals (1976 to 1982 in City Hospital Nagyatad and 1983 to 1988 in Hungarian State Railways Hospital Szolnok). Patients were divided into groups according to degree of inflammation of appendix. Length of the elapsed time from the appearance of first symptoms to operation and degree of inflammation of the appendix were fixed. It is found that time-factor did not appear to be the most important determinant of degree of inflammation in a certain part of cases. PMID- 2326068 TI - [Stress tolerance in patients with right ventricular infarct during the rehabilitation period]. AB - 199 patients with myocardial infarction were divided into 4 groups according to the localisation of necrosis (anterior, inferior, anterior + right ventricle, inferior + right ventricle). Exercise capacity was determined by bicycle ergometer test at the beginning of rehabilitation and 3 weeks later. Exercise capacity and ejection fraction were better in case of inferior comparing with anterior infarction. There was no significant change in exercise capacity whether inferior or anterior left ventricle necrosis was accompanied by right ventricle infarction. In chronic phase of myocardial infarction exercise capacity of patients is not influenced by right ventricle necrosis accompanied by left ventricle infarction. PMID- 2326069 TI - [Simultaneous occurrence of bilateral extrauterine pregnancy and ovarian hyperstimulation syndrome following artificial heterologous insemination (differential diagnostic difficulties)]. AB - Simultaneous occurrence of bilateral extrauterine pregnancy and hyperstimulation syndrome of the ovary following artificial heterologous insemination, meaning difficulty in the differential diagnosis, is described. In connection with the case the protocol of induction of ovulation used regularly by the authors is presented and the necessary monitoring model is described. If the observation is suitable the emergency operation of a patient in bad physical condition can be avoided in the opinion of the authors. The close correlation between the hyperstimulation of the ovary and early-pregnancy as well as the favourable spontaneous healing disposition of the cystic alteration is highlighted. It is held important that a laparotomy performed in connection with acute abdominal symptoms should be conservative for the genitals--possibly even in case of extrauterine pregnancy--in order to maintain the chances for a later fertility. PMID- 2326070 TI - [Nursing 1990--back to the future?]. PMID- 2326071 TI - [20 years old ... practice paper 1989]. PMID- 2326072 TI - [Non-smokers: modern, independent, environmentally aware]. PMID- 2326073 TI - [Coercion and freedom in psychiatry]. PMID- 2326074 TI - [Clinical aspects of the detection of early arthrosis. Degenerative changes of the menisci of the knee joint]. AB - In a series of 420 persons the knee and hip joints were examined anamnestically and clinically. From this series, 146 persons were selected for further examination of one knee joint by means of magnetic resonance imaging (MRI) on a 1.5 Tesla Magnetom; there was a wide range of indications. Only four MRIs showed no pathological findings in the cruciate ligaments, cartilage surfaces, or menisci. Fifty-one menisci showed grade 3 degenerative changes. In 29 cases (57%), isolated horizontal tears were found, in 1 case (2%) an isolated vertical tear, and in 3 cases (6%) combined horizontal and vertical tears. The correlation of the degenerative changes in the medial meniscus and age was significant (P = 0.01). There was no correlation between the degenerative changes of the medial meniscus and femoral or tibial changes of the cartilage. In this series, there was no significant connection between degenerative changes of the medial meniscus and the previously accepted clinical symptomatology. PMID- 2326075 TI - [Possibilities for early detection of arthroses using imaging procedures]. AB - Today early detection of osteoarthrosis (OA) must imply the recognition of initial changes of articular cartilage before radiological signs appear. A noninvasive imaging technique must meet the demands of imaging the articular cartilage layer with high contrast and surface irregularities (fibrillation) and changes within the substance. This can only be achieved by magnetic resonance imaging (MRI) with optimized conditions (3D-gradient echo sequence). In 80 patients, 62% of them without radiological signs of OA, articular cartilage of the knee joint was prospectively (70 patients) and retrospectively (10 patients) investigated with MRI and compared with the arthroscopic findings. Normal cartilage could be distinguished from pathological conditions with a specificity of more than 90% when evaluating surface morphology, signal homogeneity and, above all, signal intensity (40 patients). Full-thickness defects were identified in all cases. Cartilage fibrillation of differing depths (grades 1-3) could not be differentiated with a sufficient degree of reliability and requires a more subtle evaluation method by means of improved software. Thus, the noninvasive recognition of early pathological changes of articular cartilage in patients without radiological signs of OA has become possible. PMID- 2326076 TI - Differentiation-dependent expression of provirus-activated int-1 oncogene in clonal cell lines derived from a mouse mammary tumor. AB - The int-1 mammary oncogene is frequently activated by proviral insertion in mouse mammary tumors. To characterize the target cell for the oncogenic action of int 1, we have isolated permanent cell lines with distinct morphologies and differentiation characteristics, starting from a tumor with a rearranged int-1 gene. Polygonal cells had retained many differentiation markers of epithelial cells and produced adenocarcinomas upon transplantation in syngenic mice. Sphere forming-cuboidal cells are poorly differentiated and produced anaplastic tumors. Cuboidal and elongated cells were negative for epithelial markers. Cuboidal cells were poorly tumorigenic, but elongated cells produced highly malignant sarcoma like tumors. In all lines, the int-1 gene was identically rearranged due to insertion of proviral DNA of the Mouse Mammary Tumor Virus, but the expression of int-1 varied with the state of differentiation of the cells. Polygonal cells contained relatively high levels of int-1 RNA, which were not influenced by steroid hormones. In the sphere-forming-cuboidal cells, expression of int-1 was low but inducible by dexamethasone. In the cuboidal and elongated cells no expression of int-1 was detectable, showing that the continued expression of int 1 was not required for progression to more malignant cells. By immunoprecipitation, two int-1 protein species, of 42 and 40 kD were identified in polygonal and in sphere-forming-cells but not in the culture media. PMID- 2326077 TI - Regulation of stability and synthesis of EGF-receptor mRNAs encoding for intact and truncated receptor forms. AB - The EGF-receptor is a proto-oncogene encoded membrane protein related to the v erb-B oncogene product of avian erythroblastosis virus. Here we have studied the expression and stability characteristics of two forms of receptor mRNA--a 5.6 kb form that encodes for the intact transmembrane 170 kDa receptor and a 3' deleted 2.6 kb form that encodes for a 100 kDa secreted EGF-receptor. In previous studies we showed that EGF increased the synthesis of its own receptor in human cytotrophoblasts and A431 cells. Now we show that EGF stimulates the transcription of the receptor gene and blocks the degradation of transcripts, and thus elevates the level of receptor mRNA in these cells. To test the role of prior protein synthesis in these phenomena, we examined the effect of cycloheximide, and found that this reagent, either alone or in combination with EGF, leads to an increase in the level of EGF-receptor mRNA. Increases were seen in both size classes of receptor mRNA. Further analysis showed that cycloheximide enhances both synthesis and stability of receptor mRNA. While the intrinsic stability of the 3'-truncated 2.6 kb mRNA is approximately 2-fold higher than that of the 5.6 kb species, it is enhanced by more than 10-fold in the presence of cycloheximide and EGF acting in a synergistic manner. The extent of stabilization was less for the larger mRNA form. The results suggest the involvement of ligand as well as labile proteins in the control of synthesis and stability of EGF-receptor mRNA, and imply the involvement of 3' located structural features in the control of receptor mRNA stability. PMID- 2326078 TI - Cancer nurses in action. PMID- 2326079 TI - From Greentree Road. The renewal of certification of oncology nurses. PMID- 2326080 TI - Planning for a successful merger. The Health Care Group. AB - Merging your practice with another will be one of the most complex business challenges you take on. It requires that you analyze nearly every aspect of your practice's operations--and review your own personal and professional objectives. The benefits can be significant, but pitfalls loom for those who enter the merger process unprepared. We recommend that doctors give very careful consideration to their reasons for seeking a merger, and that they plan thoroughly in order to make their merger a success. PMID- 2326081 TI - Advances in computerized practice management. PMID- 2326082 TI - Transmission of HIV: a wrap-up. PMID- 2326083 TI - A turn for the worse. PMID- 2326084 TI - A cautionary tale. PMID- 2326085 TI - What is the price for personal freedom? PMID- 2326086 TI - Nursing shortage: Bush signs bill allowing foreign nurses to apply for permanent residency. PMID- 2326087 TI - [Respiratory aid using a diaphragmatic pacemaker in high paraplegia]. AB - Spastic tetraplegia due to cervical medullary injury above the origin of the phrenic nerve neurons means complete respiratory paralysis. In this case a phrenic pacemaker can be considered as an alternative to long term mechanical ventilation. An implantable 8-channel stimulation device has been developed for functional electrical stimulation of the phrenic nerves. The "Karussellstimulation" provides fatigue free stimulation for 24 hours a day. We report the case of a 12 year old girl with complete ventilatory insufficiency who underwent implantation of a phrenic pacemaker. 18 month after implantation she is independent of a conventional respirator and limits rehabilitation could be achieved. Electrophrenic respiration is of value in the rehabilitation management of tetraplegic patients with ventilatory insufficiency. PMID- 2326088 TI - [Effect of dietary non-compliance on development in phenylketonuria--studies of 14-year-old patients]. AB - 25 children with early treated PKU were studied at the age of 14 years. The IQ was higher at the age of 6-8, 10 and 14 years if the dietary control was good (75% of the control values up to 10 mg/dl) compared to children with poor control. The IQ however decreased up to the age of 14 years in both groups. Discontinuation of the diet in children with a good dietary control at the age of 6 years because of a normal EEG after phenylalanine loading causes a decrease of the IQ from 100 at 6 years to 90 at 10 years. The IQ remains stable thereafter up to 14 years. The IQ ist lower at the age of 7 or 8 years in those children in whom the discontinuation of diet is delayed because of abnormal EEG after phenylalanine loading at the age of 6 years, but remains stable up to the age of 14. According to these results a discontinuation of the diet at the age of 6 years can not be recommended even if the EEG is normal after phenylalanine load. PMID- 2326089 TI - [Persistent neonatal hypoglycemia in nesidioblastosis of the pancreas]. AB - A now 10 month old female infant suffered from persistent non ketotic neonatal hypoglycemia despite continuous intravenous application of glucose (greater than 10 mg/kg/min). There was only a transient response of blood glucose after intravenous administration of glucagon and prednisolon. Biochemical findings indicated hyperinsulinismus (insulin level of 26 mE/ml during hypoglycemia). Oral diazoxid treatment in high doses (22 mg/kg) stopped hypoglycemia episodes for several days but the newborn remained glucose infusion depended. Finally the treatment had to be interrupted because of vomiting. At the age of 4 1/2 weeks a subtotal pancreatectomy was performed. The histological examination of the pancreas confirmed the clinically suspected diagnosis of nesidioblastosis. After pancreatectomy the infant required insulin therapy. Since six months the girl is without insulin in a good condition. Despite periods of arrested head growth before pancreatectomy the psychomotoric development is normal. PMID- 2326090 TI - Sensory and autonomic measurements in idiopathic trigeminal neuralgia before and after radiofrequency thermocoagulation: differentiation from some other causes of facial pain. AB - (1) Quantitative measurements of somatosensory thresholds and skin temperature were made before (24 cases), 3-5 days after (12 cases), and 6 months after (11 cases) successful radiofrequency thermocoagulation of the proximal root and gasserian ganglion in 24 cases of idiopathic trigeminal neuralgia (TGN), 18 of whom had not previously undergone any interventional procedure; and in 3 cases of compressive non-TGN neural and 4 of non-neural facial pain at presentation. (2) There were no differences in somatosensory thresholds between the skin innervated by the affected divisions and the unaffected mirror-image areas in previously unoperated cases of TGN and non-neural facial pain ('atypical facial pain') prior to operative intervention; but there were significant differences in tactile (von Frey) thresholds in the cases of non-TGN facial pain of neural origin. (3) In TGN immediately after operation, thresholds for all modalities except cold sensation were significantly raised. Six months later, tactile and tragus pinch pain thresholds had returned to normal; but thresholds for warmth, hot pain, and pinprick remained elevated. However, in cases who had had previous procedures for TGN between 9 months and 5 years earlier, all thresholds except pinprick and possibly hot pain had returned to normal. (4) Prior to operation for TGN, the skin temperature in the affected division was significantly lower than that in the contralateral unaffected division, presumably due to vasoconstriction. In previously operated cases in whom TGN had re-appeared, cutaneous vasoconstriction was also demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326091 TI - Quantitative EMG and muscle tension in painful muscles in fibromyalgia. AB - Examinations were performed in 22 female fibromyalgic patients and in 9 healthy controls. The biceps brachii, trapezius, and tibial anterior muscles were examined electromyographically. The changes found were minor and non-specific. This implies that there is no important loss of motor units and no conspicuous muscle fiber degeneration in fibromyalgia. Our investigation also failed to demonstrate any electrically detectable muscle activity in muscles where the patients during the examination reported pain (paraspinal, trapezius and tibial anterior muscles). This means that muscle tension cannot be a prominent pathogenetic factor in fibromyalgia and that factors other than muscle tension are responsible for maintaining the pain in fibromyalgia. PMID- 2326092 TI - Critique of the Dornier HM3 lithotripter as a clinical algesimeter. AB - The power and nociceptive intensity of shock waves generated by the Dornier HM3 extracorporeal shock wave lithotripter (ESWL) are voltage dependent and suited to algesimetry in a controllable voltage range of 8-30 kV. Fidelity of the HM3 as an algesimeter was tested by: (1) In vitro measurements of shock pressure at voltages between 14 and 30 kV were recorded by a force transducer at the point of clinical focus. (2) Unanaesthetized volunteer (n = 5) assessment and VAS pain scores of shocks in the range of 10-24 kV, yielding highly significant correlations between blinded randomized shock voltage (r = 0.88), and VAS scores (r = 0.84). (3) Voltage-tolerance curves generated from 33 ASA class 1 or 2 patients undergoing ESWL treatment under epidural analgesia with 0.125% bupivacaine, fortified with a bolus epidural dose of 100 micrograms fentanyl if pain arose during treatment. Voltage tolerance was increased by 50% after an epidural bolus of 100 micrograms fentanyl (P less than 0.001). The respiratory consequences of epidural fentanyl were assessed by changes of respiratory rate and rhythm recorded from capnographic tracings of expired carbon dioxide. This study indicates that the Dornier HM3 system provides a valuable opportunity to conduct precise, quantitative measurements of induced deep truncal pain, as well as the effectiveness and respiratory cost of analgesic interventions directly applicable to the safe management of acute pain. PMID- 2326093 TI - Post-lumbar puncture headache: the relation between experimental suprathreshold pain sensitivity and a quasi-experimental clinical pain syndrome. AB - The relation between general experimental pain sensitivity and the clinical expression of post-lumbar puncture syndrome (PLPS) was examined in a prospective double-blind study of patients who underwent a lumbar puncture with a 20-gauge spinal needle. In 44 neurology patients randomized pain was induced on the middle phalanges of fingers II-IV of both hands using a tension device on the day before lumbar puncture. Pain intensity was measured using the category sub-dividing procedure. The correspondence between experimental pain stimuli and induced pain intensities could best be described by a logarithmic function. PLPS symptoms were documented in a multi-dimensional quantitative fashion using various scales. Pronounced position-dependent headache occurred in 31% of the patients. There proved to be very significant effects of experimental pain sensitivity on intensity and duration of position-dependent headaches, as well as on vegetative symptoms of PLPS (P less than or equal to 0.01). The results provide an explanation for the varying interindividual manifestation of PLPS symptoms, in addition to factors already identified such as the size of needle used in individual patients. PMID- 2326094 TI - Graded chronic pain status: an epidemiologic evaluation. AB - In epidemiologic research on chronic pain, differentiation of recurrent, persistent and disabling pain states is critical in the investigation of burden, natural history, effective intervention and causal processes. We report population-based data concerning the development and evaluation of a graded classification of pain status. In a probability sample of 1016 health maintenance organization enrollees, recurrent or persistent pain was observed in 45%; severe and persistent pain in 8%; severe and persistent pain with 7 or more days of pain related activity limitation in 2.7%; and severe, persistent pain with activity limitation and 3 or more indicators of pain dysfunction in 1.0% of the population sample. Graded chronic pain status was associated with psychological impairment, unfavorable appraisal of health status, and frequency of use of pain medications and health care. The presence of severe and persistent pain increased the likelihood of multiple indicators of pain dysfunction, but there was considerable heterogeneity in pain dysfunction among persons with comparable pain experience. Our data suggest grading chronic pain in terms of 3 axes: time (persistence); severity; and impact (disability and dysfunctional illness behaviors). PMID- 2326095 TI - An emotional component analysis of chronic pain. AB - The present study sought to determine the relative contribution of frustration, fear, anger and anxiety, to the unpleasantness and depression pain patients experience. Sixty-nine women and 74 men, with an average age of 47 years, were included. Patients underwent psychological evaluation which included use of the Minnesota Multiphasic Personality Inventory (MMPI), Beck Depression Inventory (BDI), and 7 visual analog scales (VAS) measuring degree of emotional unpleasantness, pain intensity, anxiety, frustration, fear, anger and depression. Test-retest reliability coefficients were significant for the negative feeling VAS yielding an average reliability coefficient of 0.82. Analyses relating the negative feeling state VAS to pain unpleasantness and depression indices from the MMPI (scale 2) and BDI (sum score) yielded significant canonical correlations. Multiple regression was used to clarify the relationships between negative feeling VAS, pain-related unpleasantness, and indices of depression. After statistically controlling for intensity of pain, anxiety and frustration predicted unpleasantness. Regression analyses indicate that anger is an important concomitant of the depression that pain patients experience. The results suggest that anger and frustration are critical concomitants of the pain experience. Treatment techniques specifically targeting anger and frustration in these patients may prove efficacious. PMID- 2326096 TI - Differential responses of nociceptive vs. non-nociceptive spinal dorsal horn neurones to cutaneously applied vibration in the cat. AB - Extracellular single-unit recordings were made from dorsal horn neurones in the lumbar spinal cord of cats which were anaesthetized or were anaemically decerebrated. Each neurone was classified functionally as wide dynamic range (WDR), non-nociceptive, nociceptive specific or proprioceptive. Vibration was then applied to the hind limb using a feedback-controlled mechanical stimulator. WDR neurones had 3 distinct types of response to vibration (80 Hz: 0.3-1.0 mm): excitation, depression and a biphasic response consisting of excitation followed by depression. The type of response depended upon the location of the stimulator probe. With the stimulator probe placed inside that part of the receptive field from which low intensity, non-vibrational cutaneous stimuli elicited excitation, 35 neurones were excited by the vibratory stimulation, none was depressed and 4 showed the biphasic response. On the other hand, when the probe was positioned outside the receptive field for low intensity stimuli, 7 WDR neurones were excited, 164 showed depression or the biphasic response and 7 were unaffected. On going activity and activity evoked by iontophoretic application of glutamate were decreased during the depressant response and during the depressant phase of the biphasic response. In terms of non-nociceptive neurones, all (n = 30) were excited by vibration; depressant or biphasic responses were not observed. Excitation was elicited by placing the probe either inside or outside the receptive field for non-vibrational stimuli. All nociceptive specific neurones (n = 3) were depressed by vibration regardless of the position of the stimulus. All proprioceptive neurones (n = 12) were excited by vibration. The predominantly depressant effect of vibration on nociceptive neurones vs. the predominantly excitatory effect on non-nociceptive neurones prompts us to suggest that the increase in pain threshold and the clinical analgesia elicited by vibration may be mediated at the spinal level by a decrease in the rate of firing of nociceptive neurones and/or by excitation of non-nociceptive neurones. PMID- 2326098 TI - Influence of polarity on dose-response relationships of intrathecal opioids in rats. AB - Dose-response curves were constructed for intrathecal morphine (M), oxymorphone (OM), hydromorphone (HM), diamorphine (DM), 14-hydroxydihydromorphine (OHM), oxycodone (OC), hydrocodone (HC) and fentanyl (F). Intrathecal catheters were placed in 69 rats under halothane/N2O anaesthesia. After recovery, baseline hot plate and tail flick latencies were measured, and a dose of opioid was given. Hot plate and tail flick latencies were assessed at 5, 15, 30, 60, 90, 120 min and then hourly until they returned to within 25% of baseline. Response latencies were converted to per cent of maximum possible effect (% MPE) and the area under the % MPE X time curve was taken as the response. This measure includes information about both potency and duration of action. Each rat received 3 opioids and saline at intervals of 2-3 days. On a fifth occasion, the animal's first treatment was repeated. Each opioid was studied over an 8-fold dose range. Results of both hot plate and tail flick were best described by a model including log(dose), a component due to development of tolerance over the 5 experimental days, and an among-rat variation term. In the hot plate test, doses equieffective in producing a response (AUC) over the dose range studied were in the order OHM less than OM less than HM less than M less than F less than DM less than HC less than OC. Slopes of the log(dose)-response curves were similar for all drugs except OHM, which had a steeper slope. A model is proposed in which hot plate and tail flick latencies are prolonged while CSF concentrations of a drug are above its minimum effective concentration, and drug is cleared from the CSF by a first order process, possibly uptake into the spinal cord and removal via the blood. This model predicts that log(dose)-response curves will be linear, as was observed, with slopes inversely proportional to the rate constant for clearance from CSF. According to this model the steeper slope of the OHM log(dose)-response may be interpreted as indicating slower clearance from CSF. OHM has the lowest octanol/pH 7.4 buffer distribution coefficient (0.34) of all opioids studied, possibly leading to a lower rate of uptake into the spinal cord. PMID- 2326097 TI - Effect of intrathecal tizanidine on antinociception and blood pressure in the rat. AB - Experiments were performed in rats to determine if the alpha 2-adrenergic agonist tizanidine has an antinociceptive effect when injected intrathecally, and whether the analgesia is accompanied by changes in blood pressure. Rats were chronically implanted with catheters in the lumbar subarachnoid space. Antinociception was evaluated in conscious rats with the tail-flick test. Increasing tizanidine doses produced increases in analgesic efficacy, with 25 micrograms producing a significant long-lasting antinociception. This tail-flick analgesia was very similar to that produced by clonidine (25 micrograms) and morphine (8 micrograms) in peak effect and duration. Doses as high as 250 micrograms produced only a transient hind limb motor dysfunction in 43% of the animals. Daily injections of 25 micrograms tizanidine over 5 days produced a decrease in antinociception, with the peak effect at day 5 at 59% of that at day 1. Blood pressure, in rats lightly anesthetized with halothane, was not affected by tizanidine injections up to 250 micrograms. Tizanidine appears to be a promising non-opiate analgesic for intrathecal usage. PMID- 2326099 TI - P-A-I-N reviews. PMID- 2326100 TI - Comment on Hopkins and Charters, 'An unusual case of causalgia. Relevance to recent hypothesis on mechanism of causalgia' (Pain, 37 (1989) 93-95) PMID- 2326101 TI - The past is prologue. PMID- 2326102 TI - Changing liability of the nurse over the past decade. AB - Many changes have occurred over the past decade in legal responsibilities of nurses. These reforms have led to attitude changes toward nurses by the legal, medical, and public realms. To avoid legal charges of negligence, nurses must keep abreast of the rapidly changing areas of instrumentation, documentation, and patient care. PMID- 2326103 TI - Pain diaries, journals, and logs. AB - Writing pain journals serves several purposes for both the patient and the nursing staff. The diaries reveal feelings and experiences on a subjective level, and medications, pain duration, and other factual information on an objective level. The benefits can be immediate and therapeutic or ongoing and retrospectively useful to the patients. Information can be used by the nursing staff to better meet the patient's physical and emotional needs. PMID- 2326104 TI - Situational leadership: a management system to increase staff satisfaction. AB - Using the principles of Situational Leadership, nurse managers can deal with people and situations effectively and flexibly--helping to retain nurses on their units. Based on the manager's assessment of the nurse's ability and willingness for a specific task, each nurse falls into one of four readiness quadrants. Each quadrant predicts a corresponding leadership style: telling, selling, participating, or delegating. Nurse managers need to use different combinations of task behavior and relationship behavior for each corresponding leadership style. PMID- 2326105 TI - A successful combination: preadmission testing and preoperative education. AB - With the advent of prospective pricing, hospitals now have a powerful incentive to improve efficiency and reduce expenses. Prospective pricing incentives are encouraging movement of preoperative teaching out of the inpatient setting. At The Center for Hip and Knee Surgery, a 24-bed research-oriented midwestern orthopaedic hospital, we have developed and implemented an alternative approach to preadmission testing and preoperative patient education. PMID- 2326106 TI - 100 of the best articles relevant to pediatric allergy and immunology. Selected by members of the Section on Allergy and Immunology of the American Academy of Pediatrics from articles appearing in 33 medical journals between August 1, 1988 and August 1, 1989. PMID- 2326107 TI - Effects of delayed visual feedback on motor control performance. AB - The effects of delay of visual feedback on two kinds of sensorimotor tasks were investigated. On the reciprocal tapping task, accuracy of performance decreased for 200, 500, and 767 msec. delay. The number of errors for the 1000-msec. delay is smaller than those for the other three conditions of delay. On the hand writing task of both Kanji letters and English words, performance showed a large decrement with increasing delay. The most frequent kinds of error were the type of insertion of line elements or letter duplication. It was interesting that the size of written letters increased with lengthening delays of visual feedback. PMID- 2326108 TI - Instance-based clusters of fear and anxiety: is ambiguity an essential dimension? AB - Students rated instances of fear-like emotions on 34 attributes related to distinctions between fear and anxiety in the literature, and then on relative degree of fear vs anxiety produced. Instances rated most fear-like had been rated as higher than more anxiety-like instances in terms of clarity and reality of causes, but lower in terms of the clarity of understanding the situation and knowing what to do when in it. There were two distinct clusters of fear-like instances and two distinct "anxiety clusters;" the two fear clusters were more different from each other than from the two anxiety clusters in terms of ratings on these clarity-related attributes. Analysis suggested (a) that "pure fear" is less vague than anxiety in some ways but more vague in other ways and (b) that comparisons have to be qualified because emotion-labels usually encompass more than one kind of emotion. However, differences in present-centeredness and other factors may be reliable and general. PMID- 2326109 TI - Comparison of the Test of Nonverbal Intelligence and Wechsler Intelligence Scale for children--revised in rural Native American and white children. AB - The Test of Nonverbal Intelligence (TONI) and Wechsler Intelligence Scale for Children--Revised (WISC--R) were administered to 46 Native American and white students who were suspected by their classroom teachers of having learning handicaps. Pearson correlations between these sets of IQs ranged from .42 (TONI and WISC--R Performance) to .89 (WISC--R Verbal and Full Scale). PMID- 2326110 TI - Comparison of processing style and instructional style observed in physical educators and dance educators. PMID- 2326111 TI - Weinstein's Noise Sensitivity Scale: reliability and construct validity. AB - Psychometric properties (reliability, internal consistency, factor structure, and construct validity) of the Swedish version of the Noise Sensitivity Scale were satisfactory. Support for the external validity of Weinstein's findings was described. PMID- 2326112 TI - Vigilance ratios implicate biological rhythms. AB - Vigilance research has been focused on differences, yet ratios might have intrinsic, numerical significance. Reanalysis of data from Watkins' 1963 psychophysical experiment and 49 vigilance reports showed that individual and group ratios, including errors or misses: detections, were related to roots (particularly of base 1/12 and multiples), powers, e-base ratios (EBR), and fractions. Examples are given from well-known experiments of remarkably exact relationships between conditions, time periods, etc. It is suggested that these phenomena are the product of biological rhythms. Theoretical implications are briefly discussed and the advantages of ratio analysis noted, as when this method proved that criterion beta changes, given as nonsignificant, formed part of an ordered set. In a real-world application, the frequency of lane-drifts in O'Hanlon and Kelly's 1977 report is shown to follow a mathematical pattern. PMID- 2326113 TI - Exemplar effect in Mueller-Lyer decrement. AB - Coren and Girgus in 1972 had each of their subjects inspect one of four Mueller Lyer variants with the two segments set equal. In six interspersed Average Error test trials with the initial setting at zero illusion, the variants showed similar decremental rates. In 1962 Day had observed decrement when the test trials began with the segments equal; Eysenck and Slater in 1958 found no decrement when the test trials started with the segments clearly dissimilar. Present subjects addressed figures having either equal or unequal segments, and, over six trials, with and without inspection periods, came to approach the presented figures as exemplars. PMID- 2326114 TI - Relation between speed of reaction and psychometric tests of mental ability in musculoskeletal injury-prone subjects. AB - Long reaction time (RT), long choice reaction time (CRT), and low scores on psychometric tests of mental ability (MA) have in previous studies been related to musculoskeletal injuries. There has been controversy concerning the relation between slow reaction and low-grade MA recently, the old hypothesis of negative correlation between RT and MA being discussed. The aim of this study was to analyze the relation between speed of reaction and MA. For a sample of 123 volunteer healthy young men simple RT, choice RT, and spatial (block design), verbal and arithmetic components of MA were tested. A principal component analysis was performed and the factor matrix was rotated orthogonally using the varimax method. Two factors were extracted accounting for 73% of the total variance in data space. The mental ability factor, which was responsible for 70% of the variance in factor space, was comprised of components of MA and choice RT. The speed of reaction factor accounted for the remaining 30% of the variance in factor space and was comprised of simple and choice RTs. As choice RT had significant loading on the mental ability factor, the subjects having scores in the lowest quartile on both choice RT and MA total score were compared with the independent expected value by using the chi-squared test. The results of low grade MA and slow choice reaction were not independent. Accordingly, the results do not support the entire distinction between traditional mental ability or convergent thinking and speed of reaction in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326115 TI - Comparison of narrative recall in 11-yr.-old children and adults. PMID- 2326116 TI - Information-processing differences and laterality of students from different colleges and disciplines. AB - 1023 college students were assessed for hemispheric brain dominance using the paper-and-pencil test, the Human Information Processing Survey. Analysis of scores of students majoring in Advertising, Interior Design, Music, Journalism, Art, Oral Communication, and Architecture suggested a preference for right-brain hemispheric processing, while scores of students majoring in Accounting, Management, Finance, Computer Science, Mathematics, Nursing, Funeral Service, Criminal Justice, and Elementary Education suggested a preference for left hemispheric strategies for processing information. The differential effects of hemispheric processing in an educational system emphasizing the left-hemispheric activities of structured logic and sequential processing suggests repression of the intellectual development of those students who may be genetically favorable to right-hemispheric processing. PMID- 2326117 TI - Identification of peripheral visual images in a laterally restricted gaze field. AB - When the peripheral visual field is restricted or distorted, as occurs with certain spectacle lenses, the identification of objects in the periphery requires a coordinated head and eye movement. Initial experiments on the identification of peripheral images under such restrictions show that the degradation in performance is defined by a consistent additional delay in the time required to identify the image correctly. An analysis of the motor movements shows that performance is solely determined by movements of the head; eye movements are sufficiently precise and fast so they do not limit performance. A quantitative model of the identification task was developed and model simulations confirmed the experimental findings that head movement variables, specifically response latency and movement duration, uniquely determine identification performance. Hence, improved performance under these conditions must come from modifications in head-movement control either through training or adaptive processes. PMID- 2326118 TI - Attention of preschool children: electrodermal activity during auditory stimulation. AB - Electrodermal activity during passive and active listening tasks of 43 healthy preschool children (aged 4 yr., 8 mo. to 6 yr., 5 mo.) was studied. The procedure included the following phases: baseline recording (3 min.), a passive listening task, instructions, and an active listening task. An increase in mean amplitude of skin conductance response (SCR) was found during the active listening task over the level for the passive listening task over 10 trials. On the passive listening task from Trial 1 to Trial 10, habituation of mean SCR amplitude occurred. The younger children, moreover, exhibited significantly greater habituation than the older children. Habituation of mean SCR amplitude did not occur during the active listening task. No significant difference was found in mean SCR amplitude during the active listening task for the two age groups. The children seemed to pay more attention during the active listening task than during the passive listening task. The younger children, moreover, are believed to have shorter attention spans. PMID- 2326119 TI - The hand apraxia scale. AB - A scale for the assessment of hand apraxia was developed on a population of 239 institutionalized mentally retarded adults. Guttman scaling indicates adequate reliability and validity. PMID- 2326120 TI - Conceptual tempo and resolution of social conflict by children. AB - Of 55 boys between 7 and 12 yr. old, 12 most reflective (on the Impulsivity score or conceptual tempo) chose an assertive alternative on the Social Reasoning Inventory more often than the 14 most impulsive boys. The observation replicates prior work but suggests conceptual tempo as a construct has unclear relevance to social reasoning. PMID- 2326121 TI - Speech and music draw attention to the right ear in stereophonic listening. AB - This study investigated whether right-handed subjects would prefer the right ear for normal speech and the left ear for musical stimuli. Right-handed college students (9 women and 2 men) were presented two stereophonic tape recordings, one of normal speech, the other of nonlyrical, orchestral music. Subjects used an attenuator to match the intensity of signals in the left and right earphones. The subjects consistently favored the right side in both conditions. These findings are inconsistent with those of other researchers, such as Segalowitz and Plantery. However, the findings support the 1980 research of Porac, Coren, and Duncan, offering perceptual evidence of a general right-ear bias in right-handed subjects. PMID- 2326123 TI - Attention of hyperactive preschool children--electrodermal activity during auditory stimulation. AB - Electrodermal activity during passive and active listening tasks for 4 hyperactive (from 3 yr., 9 mo. to 6 yr., 2 mo.) and 43 healthy preschool children (from 4 yr., 8 mo. to 6 yr., 5 mo.) was studied. The procedure consisted of the following phases: baseline recordings (3 min.), a passive listening task, instructions, and an active listening task. The hyperactive subjects tended to exhibit lower levels of arousal, as indicated by the frequency of spontaneous responses, and more marked habituation with repeated stimuli. Also, they tended not to show the increased responsivity expected when attention is active rather than passive. Hyperactive preschool children, moreover, are believed to have shorter attention spans. PMID- 2326122 TI - Speech clarity/intelligibility: test-retest reliability of magnitude-estimation scaling. AB - The reliability of magnitude-estimation scaling as a measure of overall clarity of speech was investigated. 40 subjects (M age = 19 yr.) provided magnitude estimation responses for nine audiotaped versions of a nonsense sentence varying systematically in number of correct consonant phonemes. There was no significant difference in the magnitude-estimation responses of the subjects during two test sessions separated by one week. Analysis suggested that magnitude-estimation scaling is a reliable measure of speech clarity/intelligibility. This finding is discussed in relation to speech samples varying in aspects other than number of consonant phonemes correct and possible further clinical research applications. PMID- 2326124 TI - An adaptive (tracking) procedure for measuring visual search. AB - PEST, an adaptive (tracking) procedure originally developed for sensory research, was modified for cognitive studies with the multiple sequential frames paradigm and a letter-search task. The program which controlled stimulus presentation was designed to track the frame duration required for successful search on 75% of trials (the duration threshold). For each of the three subjects used, the threshold increased as a linear function of the number of sequentially presented frames, which varied between 1 and 10. Each tracking run was immediately followed by 40 trials with frame-exposure time fixed at the computer-selected threshold. Performance on these fixed level trials was close to the expected 75% correct. The Discussion addresses issues related to the use of the threshold measure in basic and applied cognitive research, explores the present findings about performance on fixed level trials at the computer-selected threshold, and examines the increase in duration threshold with the number of sequentially presented frames. PMID- 2326125 TI - Choice reaction time as a measure of recovery from general anesthesia. AB - The purpose of the study was to evaluate the reliability and validity of choice reaction time as a measure of recovery from general anesthesia. An experimental group of 43 patients underwent surgery under general anesthesia; they were measured before anesthesia and also 90, 150 and 210 min. after the end of anesthesia. A control group of 38 underwent the same procedure. Choice reaction time was not a valid measure of recovery from general anesthesia since the test was not reliable. PMID- 2326126 TI - Failure to acquire an inhibitory task following seizure-induced brain damage. AB - Male rats that had displayed limbic seizures following a single pair of systemic injections of lithium and pilocarpine were trained 2 months later on an operant schedule that required differential low rates of responding (DRL). The seizured rats never acquired schedules that required either 6-sec. or 12-sec. inhibition of responses following a reward; these rats displayed more perseverative responding and shorter interresponse times than controls. Histomorphology indicated severe brain damage primarily within the entorhinal cortices (and adjacent amygdala) and dorsal thalamus. PMID- 2326127 TI - Auditory sensitivity and tone-sequence reproduction in oral contraceptive users and nonusers. AB - In two stages spanning a single academic year, 10 women using oral contraceptives and 11 not using oral contraceptives were tested on their auditory threshold sensitivity to six frequencies (250, 750, 1500, 3000, 6000, and 8000 Hz) as a function of phases of the menstrual cycle. 11 women (5 users and 6 nonusers) were also tested on their ability to reproduce successively longer tone sequences. Results showed that there was little variation due to phase of the menstrual cycle, with the exception that oral contraceptive users showed lower relative thresholds at low frequencies during the postmenstrual phase. Over-all, oral contraceptive users had higher absolute and relative thresholds than nonusers, except at 3000 Hz. Although not statistically significant, results on the tone reproduction test showed an enhanced ability to reproduce tones during the premenstrual phase for women using oral contraceptives. Results are discussed in relation to previous findings. PMID- 2326128 TI - Developmental characteristics of figure drawings made by boys and girls ages five through eleven. AB - 526 children from the ages of 5 yr. through 11 yr. (257 boys and 269 girls) responded when asked to draw the figure of a man. Of the 68 characteristics investigated the girls' responses were significantly different from the boys' on 41 items (60%) while boys' responses were significantly different on 28 items (41%). Although there were significant differences in some responses they were not necessarily indicative of higher levels of performance. Given the number of boys and girls participating and the number of significant differences, the over all significant difference was 0. There were, however, many significant differences found in the drawings made by boys and girls ages 5, 6 and 9 yr. PMID- 2326129 TI - Effect of alcohol on visual constancy values and possible relation to driving performance. AB - The effects of the constancy phenomena in vision seem to be to provide information about the environment which is not solely dependent upon the characteristics of shape or size of the retinal image but which is modified by the brain to appear closer to the idealized characteristics of the real object. There is a regression away from the retinal image towards the actual object's characteristics. A plate viewed from an angle tends to look more like a disc than would be predicted from the geometry of perspective. This ability of the brain to impose conditions on perception is a high-level process which may be adversely affected by the depressive action of alcohol on the nervous system. In this case, objects such as road signs, etc. would tend to look smaller and so more distant than when sober if regression is inhibited. Drivers' reactions may be delayed if hazards are seen smaller and further away, thereby increasing the possibility of accident. This research indicates a reduction in phenomenal regression after ingestion of alcohol. There are implications for accident-rates in driving or in industry. PMID- 2326130 TI - Geophysical variables and behavior: LX. Lonquimay and Alhue, Chile: tension from volcanic and earthquake hazard. AB - This study assesses the effect of trait anxiety scores on subjects' responses to volcanic eruption hazard and earthquake hazard in Lonquimay and Alhue, respectively. Lonquimay is located in the southern Chilean Andes and Alhue is located in central Chile in the Coastal Range. The former was afflicted by a volcanic eruption which commenced on Christmas Day 1988 and the latter by an earthquake on March 3, 1985. Expectations of high damage and fear from a radio hazard prediction were associated with high trait-anxiety scores in the Alhue sample while positive adjustments to extenuate the hazard effect reached significance for the Lonquimay sample. PMID- 2326131 TI - Perception of enclosure effects of architectural surfaces in a large scale interior space. AB - It was hypothesized that the perceived enclosure effect of spaces would be dependent upon the explicitness of presented architectural surfaces according to the 1961-1970 model of Thiel. It was also hypothesized that the contribution of the surfaces would adhere to theoretical weights proposed by Thiel. It was further hypothesized that the perceived contribution of the surfaces to enclosure would be similar for men and women. 20 women and 10 men were presented 24 line drawings in one-point, eye-level perspective of the same furnished and occupied interior space. The line drawings differed only in the absence or presence of floor, wall, or ceiling surfaces. On an initial task the spaces represented by the drawings were ordered by the subjects from least enclosed (most open) to most enclosed (least open). In a second task the surfaces in a diagram were ranked according to their relative importance in determining the perception of the enclosing effect. The hypotheses were confirmed, and so provided support for the model that the explicitness of perceived surfaces contribute differentially to the perception of the openness of an environment. PMID- 2326132 TI - Subjective comparisons of auditory distortion. AB - To assess the accuracy of comparing different levels of distortion when levels are well above threshold, judgments were elicited from 340 subjects using two test tones of similar harmonic distribution in terms of frequency. Even though the total level of distortion in one of the tones had been reduced, subjects could not invariably select the less distorted tone in a comparison. This was true even for those subjects who stated that they could tell that the two tones sounded different from each other. There are implications concerning the validity of subjects' reports in making auditory estimations of 'quality' between signals. PMID- 2326133 TI - Validity of visually recorded temporal-distance measures at selected walking velocities for gait analysis. AB - The purpose of this study was to examine the validity of measures of temporal distance in a clinical analysis of gait. Data were collected from 15 normal subjects by one examiner. Equipment consisted of a 10-meter laminated walking track, dictaphone, metronome, and ink markers. The number of errors at four walking speeds were examined using a standardized analysis of gait. Analysis of variance showed a significant number of errors between the first and last halves of the measurement distance and among the four walking velocities. Post hoc analysis using the Scheffe test indicated significant differences in the mean number of errors at the velocities of 60 and 75 versus 25 and 40 m.min-1. An F test for simple effects indicated a significant number of errors occurred during the second half of the measured distance and at walking velocities of 60 and 75 m.min-1. These results indicate that the gait analysis is valid for measurements taken at all of the walking velocities only when recorded over a three-meter distance and only at the velocities of 25 and 40 m.min-1 over a six-meter distance. PMID- 2326134 TI - Subjective expectations of the acceleration of time with aging. PMID- 2326135 TI - Viewing position and eye-hand preference effects upon anticipation of coincidence. AB - These three experiments investigated the effects of the performer's viewing position (from the side or front) of an apparently approaching stimulus (Bassin Anticipation Timer) upon error (AE, CE, VE) in anticipation of coincidence. Exps. 1 and 2 gave no evidence for the superiority of any viewing position for adults. Exp. 3 assessed ipsilateral (right eye and hand) and contralateral (left eye and right hand) preferences of children (ages 5.5 to 10.1 yr.). No evidence was obtained to support the hypothesized increment in performance for contralaterals when the "lead-eye" was the preferred eye; in fact, the descriptive data suggested the reverse. Those with ipsilateral preferences evidenced less AE and VE than contralaterals. Display speed affected performance so greater accuracy occurred at the fast speed in Exps. 1 and 3 whereas the two slower speeds led to less error in Exp. 2. The differential speed effect was interpreted to represent an experience/skill factor. PMID- 2326136 TI - Restricting the field of view: perceptual and performance effects. AB - Visual perception involves both the high acuity of foveal vision and the wide scope of overlapping peripheral information. The role of peripheral vision in competent performance of the adult visuomotor activities of walking, reaching, and forming a cognitive map of a room was examined using goggles which limited the scope of the normal field of view to 9 degrees, 14 degrees, 22 degrees, or 60 degrees. Each restriction of peripheral field information resulted in some perceptual and performance decrements, with the 9 degrees and 14 degrees restriction producing the most disturbance. In addition, bodily discomfort, dizziness, unsteadiness and disorientation, were reported as the subjects moved around with restricted fields of view. PMID- 2326137 TI - Is a spate of suicides a cluster? PMID- 2326138 TI - Similar processing of real- and subjective-contour Poggendorff figures by men and women. AB - Measures of illusion magnitude for a real-contour and two subjective-contour Poggendorff figures were obtained from 42 men and 42 women. Although magnitudes of illusion differed as a function of figure type, male-female differences in magnitude of illusion did not vary across figures or judgment orders. Also, correlations among the illusions observed for three types of figures did not differ for men and women. These data are consistent with the view that real- and subjective-contour Poggendorff figures evoke similar processing strategies and that sex differences, when observed, are probably the result of differences in cognitive-judgmental strategy rather than differences in the optical and neural properties of the visual system. PMID- 2326139 TI - Geophysical variables and behavior: LIX. The seasonal variation in suicide rates: three studies. AB - The seasonal variation in suicide in the USA was not more pronounced in 1980 in northern regions but was more clear for married people than for those with other marital statuses. The seasonal variation in suicide was not associated with the gross domestic product of the region. PMID- 2326140 TI - Effects of lateral ball location, grade, and sex on catching. AB - To investigate the effects of lateral movement on the quality and quantity of catching as they interact with age, 108 children from Kindergarten through Grade 4 were tested. A ramp was constructed which slowed the descent of the 4-in. fleece ball so that it took 1.8 sec. to arrive at the child's location. Each ball could be delivered to one of five different locations in relation to the child. The child practiced five times, with balls coming in a random sequence to each location, the center of the ramp, 1 ft. and 2 ft. each to the right and left of the center. An increase in number of catches made and in the quality of the performance based on McClenaghan and Gallahue's evaluation were associated with grade. The locations 2 ft. from the center produced the fewest catches within a grade, but 1 ft. from center produced more catches from kindergarteners than the center location and occasionally for upper grades. Evaluations of the performances showed a steady improvement across grades, but there was no effect on the evaluation of catching performance of ball location within a grade. Children appear to be at a preferred stage. PMID- 2326141 TI - Influence of physical activity on concentration among junior high-school students. AB - The level and quality of concentration were tested before and after each lesson in one class session. Two of the four classes participated in physical education activities, and the other two studied science. Each subject matter was studied the beginning and at the end of the school day. The research design was 2 x 2 x 2 factorial (two subject matters, two times of the school day, and as a repeated measure two times of test for each group at the beginning and end of each lesson). The level and the quality of concentration found at the end of each lesson were significantly higher than at the beginning. The subject matters did not influence concentration. It may be concluded that the time of day was the main influence on concentration, so teachers' claims against physical education activity lessons can be rejected. The increase in concentration toward the end of the lesson implies the need for careful lesson planning or even the consideration of increasing duration of lessons. PMID- 2326142 TI - Relationship between two different measurements of field-dependence and athletic performance of adolescents. AB - Two different measures were used to test field dependence-independence, Group Hidden Figures Test and Portable Rod and Frame Test. The purpose of the study was to compare the advantages of these two measures in differentiating among adolescents who are active in individual and team sports and those who are not. 94 adolescent boys and girls were divided into three groups, as follows: 33 in individual sports, 31 in team sports, and 30 nonathletes. No correlation was found between the two measures. The Portable Rod and Frame Test was the better instrument for distinguishing among the groups. This test requires use of visual vs proprioceptive information to perceive the body's spatial orientation. The Group Hidden Figures Test requires more analytical intelligence. Since there are relationships among awareness of the body, spatial orientation, and physical activity of athletes, the Portable Rod and Frame Test seems to be more applicable to the task of distinguishing between and among athletes and nonathletes. PMID- 2326143 TI - Contemporary opinions on health issues: another look. AB - In a comparison of 802 undergraduates, in the main between 17 and 23 yr. old, with 211 physicians who responded to an Hippocrates survey, most agreed that a mother should be informed by physicians that her teenage daughter is pregnant, but students were less inclined than physicians to misrepresent to an insurance company the reason for a screening test, and more in favor than physicians of acknowledging an error in medication. Understanding of values is desirable as is their recognition of influences on the future of society. PMID- 2326144 TI - Discriminating rigid from nonrigid motion: minimum points and views. AB - Theoretical investigations of structure from motion have demonstrated that an ideal observer can discriminate rigid from nonrigid motion from two views of as few as four points. We report three experiments that demonstrate similar abilities in human observers: In one experiment, 4 of 6 subjects made this discrimination from two views of four points; the remaining subjects required five points. Accuracy in discriminating rigid from nonrigid motion depended on the amount of nonrigidity (variance of the interpoint distances over views) in the nonrigid structure. The ability to detect a rigid group dropped sharply as noise points (points not part of the rigid group) were added to the display. We conclude that human observers do extremely well in discriminating between nonrigid and fully rigid motion, but that they do quite poorly at segregating points in a display on the basis of rigidity. PMID- 2326145 TI - Studies in auditory timing: 1. Simple patterns. AB - Listeners' accuracy in discriminating one temporal pattern from another was measured in three psychophysical experiments. When the standard pattern consisted of equally timed (isochronic) brief tones, whose interonset intervals (IOIs) were 50, 100, or 200 msec, the accuracy in detecting an asynchrony or deviation of one tone in the sequence was about as would be predicted from older research on the discrimination of single time intervals (6%-8% at an IOI of 200 msec, 11%-12% at an IOI of 100 msec, and almost 20% at an IOI of 50 msec). In a series of 6 or 10 tones, this accuracy was independent of position of delay for IOIs of 100 and 200 msec. At 50 msec, however, accuracy depended on position, being worst in initial positions and best in final positions. When one tone in a series of six has a frequency different from the others, there is some evidence (at IOI = 200 msec) that interval discrimination is relatively poorer for the tone with the different frequency. Similarly, even if all tones have the same frequency but one interval in the series is made twice as long as the others, temporal discrimination is poorer for the tones bordering the longer interval, although this result is dependent on tempo or IOI. Results with these temporally more complex patterns may be interpreted in part by applying the relative Weber ratio to the intervals before and after the delayed tone. Alternatively, these experiments may show the influence of accent on the temporal discrimination of individual tones. PMID- 2326146 TI - Studies in auditory timing: 2. Rhythm patterns. AB - Listeners discriminated between 6-tone rhythmic patterns that differed only in the delay of the temporal position of one of the tones. On each trial, feedback was given and the subject's performance determined the amount of delay on the next trial. The 6 tones of the patterns marked off 5 intervals. In the first experiment, patterns comprised 3 "short" and 2 "long" intervals: 12121, 21121, and so forth, where the long (2) was twice the length of a short (1). In the second experiment, patterns were the complements of the patterns in the first experiment and comprised 2 shorts and 3 longs: 21212, 12212, and so forth. Each pattern was tested 45 times (5 positions of the delayed tone x 3 tempos x 3 replications). Consistent with previous work on simple interval discrimination, absolute discrimination (delta t in milliseconds) was poorer the longer the intervals (i.e., the slower the tempo). Measures of relative discrimination (delta t/t, where t was the short interval, the long interval, or the average of 2 intervals surrounding the delayed tone) were better the slower the tempo. Beyond these global results, large interactions of pattern with position of the delayed tone and tempo suggest that different models of performance are needed to explain behavior at the different tempos. A Weber's law model fit the slow-tempo data better than did a model based on positions of "natural accent" (Povel & Essens, 1985). PMID- 2326147 TI - Use of segment arrays to evaluate the strength of angular induction. AB - The contribution of local and global influence on angular induction was evaluated by varying the orientation of individual segments that were organized into an array. It was found that some of the misprojection of an oblique is determined by the orientation of the individual segments, and some by the overall configuration of the segments into two parallel bands. These results are integrated into a model that views angular induction as a lateral bias among orientation-sensitive neurons, with global influence differing from local influence only as a matter of scale. PMID- 2326148 TI - Spatial reference in weightlessness: perceptual factors and mental representations. AB - The role of gravity in spatial coordinate assignment and the mental representation of space were studied in three experiments, varying different perceptual cues systematically: the retinal, the visual background, the vestibular, and proprioceptive information. Verbal descriptions of visually presented arrays were required under different head positions (straight/tilt) and under different gravitational conditions (gravity present/gravity absent). The results of two experiments conducted with 2 subjects who participated in a space flight revealed that subjects are able to adequately assign positions in space in the absence of gravitational information, and that they do this by using their head-retinal coordinates as primary references. This indicates that they cognitively adapted to the perceptually new situation. The findings from a third experiment conducted with a larger group of subjects under a condition in which the gravitational information was present but irrelevant to the task being solved (subjects were in a horizontal supine position) show that subjects, in general, are flexible in using cues other than gravitational ones as references when the latter cannot serve as a referential system. These findings, together with the observation that consistent spatial assignment is possible even immediately after first exposure to the perceptually totally novel situation of weightlessness, seem to suggest that the mental representation of space, onto which given perceptual information is mapped, is independent of a particular percept. PMID- 2326149 TI - The growth of lexical constraints on spoken word recognition. AB - In this study, we examined the influence of various sources of constraint on spoken word recognition in a mispronunciation-detection task. Five- and 8-year olds and adults were presented with words (intact or with word-initial or noninitial errors) from three different age-of-acquisition categories. "Intact" and "mispronounced" responses were collected for isolated words with or without a picture referent (Experiment 1) and for words in constraining or unconstraining sentences (Experiment 2). Some evidence for differential attention to word initial as opposed to noninitial acoustic-phonetic information (and thus the influence of sequential lexical constraints on recognition) was apparent in young children's and adults' response criteria and in older children's and adults' reaction times. A more marked finding, however, was the variation in subjects' performance, according to several measures, with age and lexical familiarity (defined according to adults' subjective age-of-acquisition estimates). Children's strategies for responding to familiar and unfamiliar words in different contexts are discussed. PMID- 2326150 TI - Signal detectability in the presence of monotic or dichotic noise bands of equal or unequal levels. AB - The application of the power-spectrum model of masking to the detectability of a signal masked by dichotic noise was investigated in three experiments. In each experiment, the signal was a 2-kHz sinusoid of 400-msec duration, masked by either one or two 800-Hz wide bands of noise presented singly or in pairs. In Experiment 1, we compared the detectability of a diotic signal masked by dichotic noise with the detectability of a monaural signal masked by each of the noises separately. The spectrum level of the noise was 35 dB SPL. For dichotic presentations, the signal was sent to both ears while pairs of noise bands, one below and one above the signal frequency, were presented together, one band to each ear. Threshold levels with the dichotic stimuli were lower than or equal to the thresholds with either ear's stimulus on its own. Similar dichotic stimuli were used in Experiment 2, except that the signal frequency was nearer to one or the other of the bands of masking noise, and the noise had a spectrum level of 50 dB SPL. In Experiment 3, thresholds were obtained with two sets of symmetrically and asymmetrically placed notched-noise maskers. For one of these sets, the spectrum level of both noise bands was 35 dB SPL; for the other set, interaural intensity differences were introduced in the form of an inequality in the levels of the noise bands on either side of the signal. In one ear, the spectrum level of the lower frequency noise band was 35 dB SPL and the spectrum level of the higher frequency noise band was 25 dB SPL, whereas in the other ear, the allocation of noise level to noise band was reversed. The dichotic thresholds obtained with the unequal noise maskers could be predicted from the shapes of the auditory filters derived with equal noise maskers. The data from all three experiments suggest that threshold signal levels in the presence of interaural differences in masker intensity depend principally on the ear with the higher signal-to-masker ratio at the output of its auditory filter, a finding consistent with the power-spectrum model of masking. PMID- 2326151 TI - Habituation to irrelevant speech: effects on a visual short-term memory task. AB - The Baddeley and Hitch (1974) formulation of short-term or working memory embodied a phonological store within the articulatory loop component of the model. Later formulations specifically postulated an acoustic filter that endowed only speech-like stimuli with obligatory access to this phonological store. This paper presents evidence that this phonological store may have two filters, one of which is subject to habituation and can therefore attenuate the entry of irrelevant speech, thus undermining the obligatory access assumption of the model. An experiment is reported in which subjects were presented with a habituation period comprising 20 min of irrelevant speech--speech to be ignored by the subject--before a test phase in which a visually presented serial recall task with concurrent irrelevant speech was performed. The effect of irrelevant speech, which impairs performance on the primary task when there is no habituation phase, is reduced markedly in those conditions where the speech used in the habituation phase is the same as that used in the test phase, if the irrelevant speech is in a language different from that presented during the subsequent trials or if the habituator is a hummed version of the irrelevant speech passage. When a nonspeech sound (pink noise) is used in the habituation phase, a large irrelevant speech effect is found in the test phase. Morris, Quayle, and Jones (1989) found that humming did not produce an irrelevant speech effect, which suggests that the first filter is permeable to humming but that the second filter is not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326152 TI - Perceived roughness as a function of body locus. AB - Twenty subjects made magnitude estimates of the roughness of grooved metallic surfaces applied to 10 body loci. To a first approximation, perceived roughness grew as a power function of groove width, in accordance with earlier studies. The exponents and intercepts (up-down position in log-log coordinates) of the power function turn out to depend strongly on body locus. The straight lines in log-log coordinates tend to diverge with groove width so that differences among body loci are especially pronounced at large groove widths. Sensitivity to roughness was greatest for the lips, fingers, and forearm, and least for the heel, back, and thigh. The rank order of the body loci in terms of roughness sensitivity closely parallels the rank order for punctate pressure sensitivity, as reported by von Frey in 1894, but apparently not for other measures of tactile sensitivity, such as vibration thresholds to various frequencies, two-point thresholds, and error of point localization. PMID- 2326153 TI - Regional splanchnic blood flow during sleep in the rabbit. AB - Regional splanchnic blood flow (rSBF) was measured in rabbits with the radioactive microsphere technique. No statistically significant changes occurred in rSBF or vascular conductances in relation to the different states of the sleep waking cycle (quiet-wakefulness, synchronized sleep, and desynchronized sleep). PMID- 2326154 TI - Role of mesangial cell contraction in adaptation of the glomerular tuft to changes in extracellular volume. AB - Different chronic states of mesangial cell contraction were induced by variation of extracellular volume in Munich-Wistar rats for 6 days to study the influence of mesangial cells on the geometry of the glomerular tuft. Stereological analysis of superficial glomeruli in volume-expanded rats (VE, treated with enalapril) and volume-reduced rats (VR, treated with indomethacin) revealed a glomerular tuft volume 28.7% smaller, and a capillary luminal volume 32% smaller in VR than in VE rats. The filtration area [defined as glomerular basement membrane (GBM) area facing fenestrated endothelium] was greatly reduced in VR rats (97 +/- 16 X 10(3) micron 2 vs 137 +/- 13 x 10(3) micron 2). The surface density (Sv) of the GBM was higher by approximately 10% in VR rats primarily due to the considerable increase in Sv of the perimesangial GBM subdivision (0.189 +/- 0.01 micron 2/micron 3 vs 0.153 +/- 0.01 micron 2/micron 3), indicating a higher degree of mesangial cell contraction in these animals. Our results suggest (1) that mesangial cell contraction plays a major role in the adaptation of the glomerular tuft to variations in extracellular volume; (2) that the relevance of mesangial cell contraction for the regulation of glomerular haemodynamics appears to be small; and (3) that the reduction in filtration area, although prominent, cannot fully account for the considerable decreases in the ultrafiltration coefficient observed by others in acute and chronic studies. PMID- 2326155 TI - A stretch-activated K+ channel in the basolateral membrane of Xenopus kidney proximal tubule cells. AB - The present study examined whether a basolateral potassium ion (K+) channel is activated by membrane-stretching in the cell-attached patch. A K+ channel of conductance of 27.5 pS was most commonly observed in the basolateral membrane of Xenopus kidney proximal tubule cells. Channel activity increased with hyperpolarizing membrane potentials [at more positive pipette potentials (Vp)]. Open probability (Po) was 0.03, 0.13, and 0.21 at Vp values of 0, 40, and 80 mV, respectively. Barium (0.1 mM) in the pipette reduced Po by 79% at a Vp of 40 mV. Application of negative hydraulic pressure (-16 to -32 cm H2O) to the pipette markedly activated outward currents (from Po = 0.01 to 0.75) at a Vp of -80 mV, but not inward currents at a Vp of 80 mV. The size of the activated outward currents (from cell to pipette) did not change by replacing chloride with gluconate in the pipette. These results indicate that a stretch-activated K+ channel exists in the basolateral membrane of proximal tubule cells. It may play an important role as a K+ exit pathway when the cell membrane is stretched (for example, by cell swelling). PMID- 2326157 TI - NJ and nursing: not so perfect together. PMID- 2326158 TI - Reserve flight nurses play important role in defense. PMID- 2326156 TI - Changes in membrane ionic conductances and excitability characteristics of rat skeletal muscle during aging. AB - Membrane electrical properties, component ionic conductances and excitability characteristics of extensor digitorum longus muscle from 3-4, 16 and 29 months old rats were measured "in vitro". Fiber diameter, membrane resistance (Rm) and membrane capacitance, increased with aging, and the increase was significant at 29 months. The increase of Rm was mostly due to a decrease of chloride conductance (GC1), whereas potassium conductance (GK) increased only slightly, at 16 and 29 months. Due to the lowered GC1, the latency of action potential increased at both ages with a consequent prolongation of the duration of action potential. Nevertheless, a decrease in the firing capability was recorded in the aged fibers. Our results indicate, that during aging, the most affected parameter of skeletal muscle fibers is GC1, although changes of this passive conductance alone cannot entirely account for the changes in the excitability characteristics recorded. PMID- 2326159 TI - The democratic imperative. PMID- 2326160 TI - AIDS and drug abuse: the implications for nursing. PMID- 2326161 TI - Scholarships and loans for nursing education. 1989-1990. PMID- 2326162 TI - Ribosomal protein S14 transcripts are edited in Oenothera mitochondria. AB - The gene encoding ribosomal protein S14 (rps14) in Oenothera mitochondria is located upstream of the cytochrome b gene (cob). Sequence analysis of independently derived cDNA clones covering the entire rps14 coding region shows two nucleotides edited from the genomic DNA to the mRNA derived sequences by C to U modifications. A third editing event occurs four nucleotides upstream of the AUG initiation codon and improves a potential ribosome binding site. A CGG codon specifying arginine in a position conserved in evolution between chloroplasts and E. coli as a UGG tryptophan codon is not edited in any of the cDNAs analysed. An inverted repeat 3' of an unidentified open reading frame is located upstream of the rps14 gene. The inverted repeat sequence is highly conserved at analogous regions in other Oenothera mitochondrial loci. PMID- 2326164 TI - The solution structure of the intramolecular photoproduct of d(TpA) derived with the use of NMR and a combination of distance geometry and molecular dynamics. AB - One and two dimensional NMR techniques have been used together with molecular modelling to obtain the solution structure for the photoproduct d(TpA)*. The NMR data confirm that the cyclobutane linkage is formed between the bonds thymine C6 C5 and adenine C5-C6. The 2D NOE data are used as constraints in a distance geometry calculation. The structures obtained show a trans-syn cyclobutane linkage and the glycosidic angles are SYN and ANTI for thymidine and deoxyadenosine, respectively. The coupling constant data are used to check the backbone torsion angles of the obtained structures. Typical torsion angles are a gamma+ and beta t for the deoxyadenosine residue. A free molecular dynamics simulation of a trans-syn d(TpA) photoproduct confirmed all these structural characteristics. PMID- 2326163 TI - Characterization of an inducible promoter system to investigate decay of stable mRNA molecules. AB - We have developed a system in which the decay of stable mRNAs can be studied without the use of inhibitors of transcription. The Drosophila hsp70 heat shock promoter linked to the bovine growth hormone (BGH) gene was used to establish stable cell lines in which the BGH gene is transcribed in a conditional manner. The BGH mRNA is synthesized only after induction at 43 degrees C. Following a brief period of re-equilibration at 37 degrees C during which transcription of the heat shock-driven gene ceases, the stable BGH mRNA decays with typical first order kinetics. Hence, the decay of the mRNA can be studied without assumptions regarding radioactive labeling of precursor pools or transcriptional inhibitors. The system is applicable to any stable mRNA. PMID- 2326165 TI - Higher transfection efficiency of genomic DNA purified with a guanidinium thiocyanate-based procedure. AB - Efficient transfection of eukaryotic cells is dependent on the purity of the transfected genomic DNA. In an attempt to obtain a more reliable method of DNA purification we have modified the widely used protocol of Blin and Stafford to include a treatment with guanidinium thiocyanate. The DNA obtained following the present protocol transfects eukaryotic cells with higher efficiency. PMID- 2326166 TI - Nucleotide and amino acid sequences of embryonic rat MAP2c. PMID- 2326167 TI - Nucleotide sequence of two genes from Helicobacter pylori encoding for urease subunits. PMID- 2326168 TI - Complete nucleotide sequence of plasmid pME2001 of Methanobacterium thermoautotrophicum (Marburg). PMID- 2326169 TI - Nucleotide sequence of porcine insulin-like growth factor. 1:5' untranslated region, exons 1 and 2 and mRNA. PMID- 2326170 TI - The primary structure of the 3-phosphoglycerate kinase (PGK) gene from Kluyveromyces lactis. PMID- 2326171 TI - Nucleotide sequence of a 16S rRNA gene for Leptospira interrogans serovar canicola strain Moulton. PMID- 2326172 TI - Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA. PMID- 2326173 TI - Nucleotide sequence of Xenopus laevis Oct-1 cDNA. PMID- 2326174 TI - Sequence of the rice mitochondrial gene for apocytochrome b. PMID- 2326175 TI - Nucleotide sequence of the psbA gene encoded by the Vicia faba chloroplast genome. PMID- 2326176 TI - Genomic sequence of a 12S seed storage protein gene from oat (Avena sativa L. cv. 'Solidor'). PMID- 2326177 TI - Ethanol precipitation of DNA with linear polyacrylamide as carrier. PMID- 2326178 TI - EclXI, a novel isoschizomer of XmaIII from Enterobacter cloacae 590 recognizing 5'-C/GGCCG-3'. PMID- 2326179 TI - Dot blot hybridization using cytoplasmic extracts is inappropriate for determination of mRNA levels in regenerating liver. PMID- 2326181 TI - Identification and sequence analysis of the ribosomal DNA promoter region of Crithidia fasciculata. AB - We have identified the promoter region of the large ribosomal DNA repeat unit of Crithidia fasciculata by northern blotting and nuclear run-on analyses. These data show that transcription starts approximately 1 kb upstream of the 18S rRNA gene. S1 protection experiments and sequence analysis of this area resulted in a precise localization of the start site. We have been unable to identify conserved sequence element(s) by a direct comparison of the crithidial RNA polymerase I promoter region and similar promoter regions of other eukaryotes; not even to the promoter region of the more closely related kinetoplastid species, Trypanosoma brucei. The absence of homology within the primary sequence of the promoter region, which is also found in other eukaryotes, might explain the observed species specificity of in vivo and in vitro rDNA transcription, since this resides in the interaction of initiation factor(s) and the core promoter domain. PMID- 2326182 TI - A factor binding GATAAG confers tissue specificity on the promoter of the human zeta-globin gene. AB - We describe the characterisation of cis-acting sequences which control the tissue specific expression of the human zeta globin gene. An extensive search for enhancer sequences in the vicinity of this gene proved negative. Instead our data demonstrate that the minimal promoter of the zeta gene is itself tissue specific. Sequences close to and possibly including the -100 CACCC and -70 CCAAT boxes display some erythroid specificity. However the principal tissue specific element is a GATAA sequence at -120 directly adjacent to the minimal promoter. Specific deletion of GATAA reduces zeta promoter activity 5 fold in erythroid but not non erythroid cells. We also demonstrate that an erythroid specific factor binds to this GATAA sequence. Furthermore this factor forms a complex with the transcription factor CP1 which we show interacts with the zeta CCAAT box. We present evidence that the zeta GATAA binding factor is equivalent to GF1 recently purified and cloned by Tsai et al [1]. The erythroid specific GATAA sequence has been found in the promoters and enhancers of a number of erythroid specific genes. Similarly we show here that the zeta globin gene relies on a GATAA sequence in its promoter to specify its expression in erythroid cells. PMID- 2326180 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2326183 TI - An archaebacterial cell-free transcription system. The expression of tRNA genes from Methanococcus vannielii is mediated by a transcription factor. AB - Our understanding of the mechanism of RNA biosynthesis in archaebacteria is limited, due in part to the inability of purified RNA polymerases to transcribe purified genes accurately in vitro. In the present study, we show that cell extracts of Methanococcus vannielii and Methanococcus thermolithotrophicus purified by gradient centrifugation synthesize a distinct transcript from templates harboring a cloned homologous tRNA(Val) and tRNA(Arg) gene. The in vitro transcripts initiate with GTP at the same sites as in Methanococcus cells. About 60% of the sequence of the in vitro RNA products was analyzed by dideoxyterminated primer extension and found to be identical with that of the precursors of tRNA(Val) and tRNA(Arg). This finding indicates that this RNA polymerase fraction both initiates and terminates transcription faithfully in vitro. After purification of a cell-free extract (S-100) of M. thermolithotrophicus by phosphocellulose chromatography, the endogenous RNA polymerase has lost its ability to transcribe the tRNA(Val) gene accurately. The activity directing specific expression of this template was reconstituted by the addition of a protein-fraction devoid of RNA polymerase activity. Thus, a transcription factor appears to be required for accurate cell-free expression of tRNA genes from M. vannielii. PMID- 2326184 TI - Isolation and functional characterization of TIF-IB, a factor that confers promoter specificity to mouse RNA polymerase I. AB - The murine ribosomal gene promoter contains two cis-acting control elements which operate in concert to promote efficient and accurate transcription initiation by RNA polymerase I. The start site proximal core element which is indispensable for promoter recognition by RNA polymerase I (pol I) encompasses sequences from position -39 to -1. An upstream control element (UCE) which is located between nucleotides -142 and -112 stimulates the efficiency of transcription initiation both in vivo and in vitro. Here we report the isolation and functional characterization of a specific rDNA binding protein, the transcription initiation factor TIF-IB, which specifically interacts with the core region of the mouse ribosomal RNA gene promoter. Highly purified TIF-IB complements transcriptional activity in the presence of two other essential initiation factors TIF-IA and TIF IC. We demonstrate that the binding efficiency of purified TIF-IB to the core promoter is strongly enhanced by the presence in cis of the UCE. This positive effect of upstream sequences on TIF-IB binding is observed throughout the purification procedure suggesting that the synergistic action of the two distant promoter elements is not mediated by a protein different from TIF-IB. Increasing the distance between both control elements still facilitates stable factor binding but eliminates transcriptional activation. The results demonstrate that TIF-IB binding to the rDNA promoter is an essential early step in the assembly of a functional transcription initiation complex. The subsequent interaction of TIF IB with other auxiliary transcription initiation factors, however, requires the correct spacing between the UCE and the core promoter element. PMID- 2326185 TI - In vitro processing of mitochondrial and plastid derived tRNA precursors in a plant mitochondrial extract. AB - A lysate of purified mitochondria of the higher plant Oenothera processes in vitro synthesized tRNA precursors to the mature tRNA size. In vitro synthesized transcripts containing genuine plant mitochondrial tRNAs and analogous RNAs from mitochondrial loci with plastid derived tRNA sequences are accurately processed by an RNAase P-like activity to yield the mature 5'-terminus. A four nucleotide deletion in the anticodon stem-loop structure, however, prevents processing. The results show that in vitro transcripts containing tRNAs from sequence fragments of plastid origin integrated in plant mitochondrial genomes can be processed correctly in plant mitochondria, if tRNA sequences and structures are intact. PMID- 2326186 TI - Capillary gel electrophoresis for rapid, high resolution DNA sequencing. AB - Capillary gel electrophoresis has been demonstrated for the separation and detection of DNA sequencing samples. Enzymatic dideoxy nucleotide chain termination was employed, using fluorescently tagged oligonucleotide primers and laser based on-column detection (limit of detection is 6,000 molecules per peak). Capillary gel separations were shown to be three times faster, with better resolution (2.4 x), and higher separation efficiency (5.4 x) than a conventional automated slab gel DNA sequencing instrument. Agreement of measured values for velocity, resolution and separation efficiency with theory, predicts further improvements will result from increased electric field strengths (higher voltages and shorter capillaries). Advantages of capillary gel electrophoresis for automatic DNA sequencing instruments and for genomic sequencing are discussed. PMID- 2326187 TI - Sequence and gene expression of rabbit cytochrome P450 IIC16: comparison to highly related family members. AB - Cytochrome P450s are heme containing proteins which evolved from an ancestral gene(s) to form a large superfamily of enzymes. We have isolated a unique cDNA from the rabbit P450 IIC subfamily, IIC16, which is 2028 bp in length. Nucleotide sequence determination indicated an ATG start codon 66 bp from the 5' end of the molecule, and an open reading frame coding for a protein of 487 amino acids. P450 IIC16 protein is greater than or equal to 90% identical in sequence to rabbit P450 IIC4, IIC5, and to the partial sequence available for IIC15. Northern and slot blot experiments demonstrated that the P450 IIC16 gene is expressed constitutively in liver, lung, testes, and kidney, and is inducible by phenobarbital in each tissue with the exception of the kidney, where mRNA levels are repressed. Alignment analysis of eight rabbit P450 IIC proteins revealed conserved and variable regions common to all IIC enzymes, and specific areas are suggested which may be important with respect to structure and function. PMID- 2326188 TI - Human ureaplasmas show diverse genome sizes by pulsed-field electrophoresis. AB - Contour clamped homogeneous field (CHEF) agarose gel electrophoresis (AGE), ramped to give linear separation of DNA molecules of 600-1600 kilobase pairs (kbp), was used to determine mobilities for full-sized genomic DNA of the serotype standard strains of the human genital mollicutes, Ureaplasma urealyticum relative to yeast chromosomal DNA markers. Indicated genome sizes (in kbp) were 760 for the four biotype 1 strains and 840-1140 for eleven biotype 2 strains. Other estimates were: 720 for Mycoplasma hominis, 1070 for Mycoplasma hyopneumoniae, 890 for Mycoplasma flocculare, 1180 and 1350 for Mycoplasma mycoides subsp. mycoides Y and GC1176-2, respectively, and 1650 and 1580 for Acholeplasma laidlawii B and PG 8, respectively. These data supplement previous evidence from CHEF AGE that the genomes of the Mycoplasmataceae are diverse in size with some larger than previously estimated from DNA renaturation kinetics. PMID- 2326189 TI - The basis of high resolution separation of small DNAs by asymmetric-voltage field inversion electrophoresis and its application to DNA sequencing gels. AB - We have previously shown that asymmetric-voltage field inversion electrophoresis produces more uniform separation for fragments between 1 and 50 kilobases (kb) than other modes of pulsed field gel electrophoresis. We now report on the basis of this phenomenon. As in conventional electrophoresis, the pulsed field mobility of DNAs between 1 and 50 kb varies with voltage in a size dependent manner. The complex migration pattern obtained with asymmetric-voltage field inversion electrophoresis reflects the difference between the mobilities of each sized fragment under the conditions used for the forward and reverse fields. We have applied this technique to DNA sequencing gels and find improvement in resolution for single-stranded fragments in polyacrylamide gels. PMID- 2326190 TI - Perturbation of DNA hairpins containing the EcoRI recognition site by hairpin loops of varying size and composition: physical (NMR and UV) and enzymatic (EcoRI) studies. AB - We have investigated loop-induced structural perturbation of the stem structure in hairpins d(GAATTCXnGAATTC) (X = A, T and n = 3, 4, 5 and 6) that contain an EcoRI restriction site in close proximity to the hairpin loop. Oligonucleotides containing either a T3 or a A3 loop were not hydrolyzed by the restriction enzyme and also showed only weak binding to EcoRI in the absence of the cofactor Mg2+. In contrast, hairpins with larger loops are hydrolyzed by the enzyme at the scission site next to the loop although the substrate with a A4 loop is significantly more resistant than the oligonucleotide containing a T4 loop. The hairpin structures with 3 loop residues were found to be thermally most stable while larger hairpin loops resulted in structures with lower melting temperatures. The T-loop hairpins are thermally more stable than the hairpins containing the same number of A residues in the loop. As judged from proton NMR spectroscopy and the thermodynamic data, the base pair closest to the hairpin loop did form in all cases studied. The hairpin loops did, however, affect the conformation of the stem structure of the hairpins. From 31P and 1H NMR spectroscopy we conclude that the perturbation of the stem structure is stronger for smaller hairpin loops and that the extent of the perturbation is limited to 2 3 base pairs for hairpins with T3 or A4 loops. Our results demonstrate that hairpin loops modulate the conformation of the stem residues close to the loop and that this in turn reduces the substrate activity for DNA sequence specific proteins. PMID- 2326191 TI - Information content of Caenorhabditis elegans splice site sequences varies with intron length. AB - A database of sequences of 139 introns from the nematode Caenorhabditis elegans was analyzed using the information measure of Schneider et al. (1986) J. Mol. Biol. 128: 415-431. Statistically significant information is encoded by at least the first 30 nt and last 20 nt of C. elegans introns. Both the quantity and the distribution of information in the 5' splice site sequences differs between the typical short (length less than 75 nt) and rarer long (length greater than 75 nt) introns, with the 5 sites of long introns containing approximately one bit more information. 3' splice site sequences of long and short C. elegans introns differ significantly in the region between -20 and -10 nt. PMID- 2326192 TI - Recent changes in the GenBank On-line Service. AB - The GenBank On-line Service provides access to the GenBank and EMBL nucleic acid sequence databases and to the Swiss-Prot and GenPept protein sequence databases. Users can query the databases by sequence similarity and annotation keywords and retrieve entries of interest. This access is available through e-mail servers, anonymous FTP, anonymous interactive login, and login to established, password protected, individual accounts. PMID- 2326193 TI - Developmentally regulated transporter in Leishmania is encoded by a family of clustered genes. AB - We have previously cloned a gene for a developmentally regulated transport protein from the trypanosomatid protozoan Leishmania enriettii. We demonstrate here that this transporter is encoded by a single family of tandemly clustered genes containing approximately 8 copies of the 3.6 kilobase repeat unit. Transcriptional mapping defines a contiguous 3.3 kilobase region of the repeat unit that encodes the mRNA. The 5' end of the mature mRNA contains the spliced leader or mini-exon previously identified in kinetoplastid protozoa, while the 3' ends of the mRNA are heterogeneous in sequence and in location of the polyadenylation site. We have identified genomic restriction fragments that flank the tandem repeat on the 5' and 3' sides and which may be linked to sequences required for expression of the gene family. Other species of Leishmania also contain sequences that hybridize to the cloned L. enriettii gene at high stringency. PMID- 2326195 TI - Role of GC-biased mutation pressure on synonymous codon choice in Micrococcus luteus, a bacterium with a high genomic GC-content. AB - The GC (G + C, or G or C)-contents of codon silent positions in all two-codon sets and three codons AUY/A (IIe), and in most of the family boxes of Micrococcus luteus (genomic GC-content: 74%) are 95% to 100% in both the highly and weakly expressed genes. In some family boxes, there is a decrease in NNC codons and an increase in NNG codons from the highly expressed to weakly expressed genes without apparent involvement of NNU and NNA codons. From these observations, we conclude that the selective use of synonymous codons in M. luteus may be largely determined by GC-biased mutation pressure and that in the highly expressed genes tRNAs would act as a weak selection pressure in some family boxes. Available data suggest that the effect of selection pressure by tRNAs on the synonymous codon choice becomes more apparent in the highly expressed genes in eubacteria with intermediate GC-contents such as Escherichia coli and Bacillus subtilis, and that the U/C ratio of the codon third positions in NNU/C-type two-codon sets in the weakly expressed genes would represent the approximate magnitude of directional mutation pressure throughout eubacteria. PMID- 2326194 TI - DNA with adenine tracts contains poly(dA).poly(dT) conformational features in solution. AB - The conformation of DNA's with adenine-thymine tracts exhibiting retardation in electrophoretic migration and considered as curved were investigated in solution by CD and RAMAN spectroscopy. The following curved multimers with adenine tracts but of different flanking sequences d(CA5TGCC)n, d(TCTCTA6TATATA5)n, d(GA4T4C)n yield CD spectroscopic features indicating a non-B structure of the dA.dT tract with similarities to polyd(A).polyd(T). We suggest that adenine-thymine bases in these multimers contain some of the distinctive conformational features of poly(A).polyd(T) probably with large propeller twist found by NMR (Behling and Kearns, 1987) and by X-ray diffraction on oligonucleotides containing a tract of adenines (Nelson et al. 1987, Coll et al; 1987; DiGabriele et al. 1989). Some elements of distinctive CD features of the contiguous adenines run are also observed in the straight multi-9-mer d(CA5GCC)n which lacks in-phase relation to the helical repeat. Despite the presence of the TpA step in the straight multimer d(GT4A4)n, the altered dA.dT conformation is not completely destroyed. Interruption of adenine tract by a guanine in d(CAAGAATGCC)n leads to a B-like conformation and to a normal electrophoretic mobility. The Raman spectra reveal a rearrangement of the sugar-phosphate backbone of dA.dT tract in the multimer d(CA5TGCC)n with respect to that of polydA.polydT. This is reflected in the presence of an unique Raman band associated to C2'-endo sugar with a predominant contribution of C1'-exo puckering which is exhibited by the multimer whereas two distinct Raman bands characterize poly(dA).poly(dT) backbone conformation. PMID- 2326196 TI - The GenBank-Server at the University of Houston. PMID- 2326197 TI - Complete cDNA sequence of rat atrial myosin light chain 1: patterns of expression during development and with hypertension. AB - Distinct atrial and ventricular isoforms of myosin light chain 1 (LC1) exist in mammals. The atrial LC1 is also expressed in fetal ventricular and skeletal muscle. Here we present a full length cDNA encoding a rat atrial LC1, based upon homology with previously reported LC1 sequences and its atrial-specific pattern of RNA hybridization in adult cardiac muscle. Atrial and ventricular RNA expression were studied during rat development and with chronic hypertension. Atrial LC1 mRNA was expressed in rat atria throughout development, and was coexpressed with ventricular LC1 mRNA in the hearts of 12-day and 16-day embryos, and in the ventricles of newborn rats (less than 24 hours). In 9 day-old neonates, atrial LC1 mRNA expression was restricted to rat atrium. In adult rats exhibiting renovascular hypertension, the expression of the atrial and ventricular LC1 mRNAs was unchanged from that seen in normal control animals. PMID- 2326198 TI - Application for PCR technology to subtractive cDNA cloning: identification of genes expressed specifically in murine plasmacytoma cells. AB - We describe a simple method for preparing a renewable source of subtractive cDNA which can be used as a hybridization probe or as insert which can be cloned into a variety of convenient vectors. This has been done by ligating a double-stranded oligonucleotide to each end of double-stranded subtractive cDNA, and then using this oligonucleotide sequence to amplify the heterogeneous population of cDNA molecules using the polymerase chain reaction and thermostable Taq DNA polymerase. This method improves the chances for identifying cDNA clones representing low abundance mRNAs that are expressed differentially. Using this approach, we have identified cDNA clones which detect three different low abundance mRNAs that are expressed in mouse plasmacytoma cell lines but not in mouse pre-B or B lymphoma cell lines. PMID- 2326199 TI - Conserved DNA structures in origins of replication. AB - According to the model of Bramhill and Kornberg, initiation of DNA replication in prokaryotes involves binding of an initiator protein to origin DNA and subsequent duplex opening of adjacent direct repeat sequences. In this report, we have used computer analysis to examine the higher-order DNA structure of a variety of origins of replication from plasmids, phages, and bacteria in order to determine whether these sequences are localized in domains of altered structure. The results demonstrate that the primary sites of initiator protein binding lie in discrete domains of DNA bending, while the direct repeats lie within well-defined boundaries of an unusual anti-bent domain. The anti-bent structures arise from a periodicity of A3 and T3 tracts which avoids the 10-11 bp bending periodicity. Since DNA fragments which serve as replicators in yeast also contain these two conserved structural elements, the results provide new insight into the universal role of conserved DNA structures in DNA replication. PMID- 2326200 TI - A highly conserved RNA folding region coincident with the Rev response element of primate immunodeficiency viruses. AB - A series of unusual folding regions (UFR) immediately 3' to the cleavage site of the outer membrane protein (OMP) and transmembrane protein (TMP) were detected in the envelope gene RNA of the human immunodeficiency virus (HIV-1, HIV-2) and simian immunodeficiency virus (SIV) by an extensive Monte Carlo simulation. These RNA secondary structures were predicted to be both highly stable and statistically significant. In the calculation, twenty-five different sequence isolates of HIV-1, three isolates of HIV-2 and eight sequences of SIV were included. Although significant sequence divergence occurs in the env coding regions of these viruses, a distinct UFR of 234-nt is consistently located ten nucleotides 3' to the cleavage site of the OMP/TMP in HIV-1, and a 216-nt UFR occurs forty-six and forty-nine nucleotides downstream from the OMP/TMP cleavage site of HIV-2 and SIV, respectively. Compensatory base changes in the helical stem regions of these conserved RNA secondary structures are identified. These results support the hypothesis that these special RNA folding regions are functionally important and suggest that the role of this sequence as the Rev response element (RRE) is mediated by secondary structure as well as primary RNA sequence. PMID- 2326201 TI - Nucleotide sequence of the human pancreatic trypsinogen III cDNA. PMID- 2326202 TI - 5S ribosomal RNA sequences of Vibrio adaptatus, V. cyclosites, V. hollisae and V. neocistes; three of these eubacteria may not be true members of the Vibrionaceae. PMID- 2326203 TI - Sequence of the Chinese hamster small heat shock protein HSP27. PMID- 2326204 TI - Nucleotide sequence encoding a 'synergistic-like' protein from the venom glands of Dendroaspis angusticeps. PMID- 2326205 TI - Xenopus laevis Cu,Zn superoxide dismutase B cDNA sequence. PMID- 2326206 TI - Nucleotide sequence of a tomato H4 histone pseudogene. PMID- 2326207 TI - Repetitive DNA sequence from the crayfish Procambarus clarkii. PMID- 2326208 TI - The gram-positive cloning vector pBD64 arose by a 1844 bp deletion of pC194 derived DNA. PMID- 2326209 TI - Isolation and identification of restriction endonuclease BsiKI. PMID- 2326210 TI - A new multi-locus DNA fingerprinting probe: pV47-2. PMID- 2326211 TI - PCR-based detection of a polymorphic BamHI site in intron 1 of the human retinoblastoma (RB) gene. PMID- 2326214 TI - Health education and the role of nurses. PMID- 2326213 TI - Leadership development and management skills: a report on the national workshop. PMID- 2326212 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2326216 TI - Serious illness in babies: which signs to look for? PMID- 2326215 TI - World HABITAT Day message. PMID- 2326217 TI - Status of nurses: students' concern. PMID- 2326218 TI - Adjustment and the student nurse. PMID- 2326219 TI - Community health nurse and dental care. PMID- 2326220 TI - Nursing care during complications in haemodialysis. PMID- 2326221 TI - Kajal Das: a case study in poliomyelitis. PMID- 2326222 TI - Research designs in Indian psychiatric nursing. PMID- 2326223 TI - [Comparative assessment of the theoretical values of vital capacity (VC) considered normal by various authors]. AB - Values of VC for "theoretical subjects" of comparable sexes, age, height were found in tables and normograms according to Baldwin, Berglund, Kory, Nikodemowicz and Morris. For each series of values, mean, standard deviation, minimal, maximal, and median values were calculated. A differential test was performed to assess significance. Statistically significant differences were found. The highest values were expressed by Morris lowest by Berglund. It seems that one should rather use real values instead of predicted and new reference values are needed due to a change of height-age relation during the past 20 years. PMID- 2326224 TI - [Cell count and immunoglobulin level in the bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis]. AB - In 49 patients with pulmonary sarcoidosis BAL differential and T-cell count, determination of IgG, IgA levels in BAL-fluid were performed. A significant increase of lymphocytes, T-cell count and levels of IgG in BAL-fluid in patients with active sarcoidosis was found. Steroid therapy significantly lowered lymphocyte counts and increased the number of macrophages. PMID- 2326225 TI - [Pulmonary circulation in chronic respiratory insufficiency]. PMID- 2326226 TI - [Value of transthoracic needle biopsy of the pleura in the diagnosis of diseases of the respiratory tract]. AB - Pleural biopsy with Abram's needle was made in 160 consecutive patients with undiagnosed pleural effusions. The sampled fluid and pleural bioptates were examined histologically, cytologically and bacteriologically. In 40 cases malignant changes were found, out of 87 with confirmed malignancy. Neoplastic cells were found in 26 patients, ovreall the diagnosis was made in 65% of lung cancer cases. Out of 41 cases of tuberculosis, pleural biopsy provided this diagnosis in 24 patients (59%). Bacteriological examination and pathological of the biopsy specimen allowed to increase the diagnostic field to 63%. Pleural biopsy did not yield any diagnosis in 9 cases of circulatory insufficiency, nor in ten patients with the following diagnoses -- pleuropneumonia, reumathoid arthritis, pulmonary thromboembolism and thoracic trauma. In 13 cases the diagnosis was not made. The diagnostic yield of pleural biopsy was similar to that reported by others. It is most valuable in cases suspected of malignancy and tuberculosis. PMID- 2326227 TI - [Analysis of the clinical course of occupational pulmonary tuberculosis in medical personnel of the Western Pomerania macroregion 1978-1987]. AB - An analysis of the clinical course of pulmonary tuberculosis diagnosed in medical personal of the Western Pomeranian macroregion in the years 1978-1987 was carried out. Most often nurses develop this disease followed by technicians and doctors. 43% of this population did not have constant contact with active tuberculosis. Symptoms led to a diagnosis in 40% of the cases. In 27 patients radiological changes involved less than two pulmonary fields. In 17 cases a three drug regimen was instituted. The average hospitalization period was lower in these cases than in other treated in this region. Also the incidence rates of at risk medical personal were lower than overal incidence rates. PMID- 2326228 TI - [Esophagotracheal fistula as a complication of radiotherapy of lung cancer]. AB - A case report is presented of a patient with lung cancer treated with chemotherapy followed by radiotherapy due to increasing dysphagia. A few months after radioterapy an esophago-tracheal fistula developed, which was diagnosed by a radiological contrast study and esophagofiberoscopy. Post mortem examination did not reveal malignant invasion of the fistula and surrounding tissues. It seems that the fistula was a late complication of radiotherapy. PMID- 2326229 TI - [Lymphoid interstitial pneumonia]. AB - Interstitial lymphoid pneumonia is a rare disease characterized by diffuse infiltration of lung tissue by lymphocytes and plasmocytes. The diagnosis can be only achieved by histopathological examination of the biopsied pulmonary tissue. It should be differentiated from malignant processes of the lymphatic system. Immunosuppression is the main line therapy, with prednisone, azatioprine and cyclophosphamide. PMID- 2326230 TI - [Long-term oxygen therapy of chronic pulmonary heart disease]. AB - Pulmonary artery pressure was measured in 70 patients with chronic bronchitis. Those with pulmonary hypertension underwent two hours oxygen therapy (flow 10-12 l/min). Those in whom a decrease of pulmonary artery pressure was observed were qualified for long term oxygen therapy (LTOT). In 32 patients which were qualified for LTOT, after a two week period of 18 hour per day oxygen therapy a decrease of systolic pulmonary arterial pressure from 336.1 mm Hg to 30.9 mm Hg and a decrease of mean pulmonary artery pressure from 25.9 to 23.2 mm Hg was observed. PMID- 2326231 TI - [The technic of inquiry in inpatient treatment of aggressive children with behavioral disorders]. AB - 336 aggressive acts of 16 children (aged 7;7-13;3) were registered and discussed with the patients during a following interview. At this they were asked for their causal attributions, their evaluations of the interventions by the staff as well as their thinking of non-aggressive alternatives. Results show that the attribution of the own aggression as following another child's provoking behavior is decreasing during therapy, whereas the ability to think in non-aggressive alternatives has increased. A comparison of improving patients with less improving patients points out that during improving therapies in the beginning children criticize the staff's interventions more often than the less improving ones do. At the end of therapy this relation is turning the other way round. PMID- 2326233 TI - [Waiting periods in Bavarian child rearing, adolescent and family counseling centers--results of a 1988 study]. AB - Child Guidance Clinics are often said to be institutions where clients have to wait for month before they get an appointment. Starting from this critique data on different aspects of waiting-lists in Bavarian Youth and Family Counselling Centers are reported. The data cover waiting-time from registration to first appointment, handling of registrations of clients in crisis-situations, a comparison of waiting-time between the year 1977 and 1988, relationship between size of the district a Counselling Center has to cover and waiting-time etc. Results probably have significance for the Federal Republic of Germany beyond Bavaria. PMID- 2326232 TI - [Neurotic delinquency in adolescence]. AB - Neurotic delinquency of adolescents is defined and demonstrated in a case report. It is an attempt to show diagnostic differences between neurotic delinquency and cases with pathological narcissism or borderline-psychopathology, although an overlap between these child psychiatric disorders exists. Getting in contact with institutions and juvenile courts there are differences in proposals, if psychotherapy is necessary or not. Therapeutic strategies and implications are shown. The 10/2 of juvenile court law is discussed. PMID- 2326234 TI - Lipid peroxidation-coupled co-oxygenation of benzo(a)pyrene and benzo(a)pyrene 7,8-dihydrodiol in human term placental microsomes. AB - The link between lipid peroxidation and benzo(a)pyrene activation was studied in microsomes isolated from human term placenta. Lipid peroxidation was initiated in the presence of NADPH by partially chelated iron. Covalently bound and free metabolites of benzo(a)pyrene or benzo(a)pyrene-7,8-diol were quantitated by radiometry and/or HPLC. Peroxidative conditions increased the amounts of benzo(a)pyrene-trans-anti-tetrol produced from benzo(a)pyrene-7,8-diol, benzo(a)pyrene-diones from benzo(a)pyrene, and protein bound metabolites from both. A reactive oxo-iron complex is proposed as an ultimate species initiating hydrogen abstraction and lipid peroxidation. It is suggested that partially chelated iron catalyzes co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8 diol by peroxyl radical in placental microsomes. This peroxidative reaction may be crucial for bioactivation of benzo(a)pyrene in human term placenta. PMID- 2326235 TI - Relative placental weight in congenital syphilis. PMID- 2326236 TI - Uptake and processing of 125I-labelled transferrin and 59Fe-labelled transferrin by isolated human trophoblast cells. AB - Trophoblast cells isolated from term human placenta and maintained as an adherent culture express surface receptors for transferrin as indicated by quantitative binding studies using 125I-labelled transferrin. The Kd was 5.3 x 10(-9) M. About 36 per cent of the total cell receptor population was found at the cell surface, the remainder being intracellular. Both 125I-labelled and 59Fe-labelled transferrin were internalized by receptor-mediated endocytosis with similar rates. Pulse-chase experiments showed that 125I-labelled transferrin was recycled and released back to the medium, whereas 59Fe accumulated intracellularly and was released slowly. Polyacrylamide gel electrophoresis followed by autoradiography revealed that 59Fe was accumulated by cells largely in the form of ferritin. A small intracellular pool of low molecular weight 59Fe was also detected. In the presence of monensin, the transfer of 59Fe to ferritin was greatly reduced. The nature and amount of 59Fe released from cells could be modulated by the incubation conditions. In the absence of chelating agents and iron salts, released 59Fe was found to be associated with a low molecular weight fraction as well as with transferrin and ferritin. The low molecular weight 59Fe readily formed a complex with added chelators such as apotransferrin, DTPA or desferrioxamine. The release of 59Fe could be increased by repeatedly changing the medium during the course of the incubation. 59Fe release from trophoblast cells exceeded the release of lactate dehydrogenase and also exceeded the release of 59Fe from 3T3 fibroblasts, suggesting a cell-specific process. PMID- 2326237 TI - Lack of innervation of human umbilical cord. An immunohistological and histochemical study. AB - Using a panel of antibodies (monoclonal as well as polyclonal) to nerves, nerve tissue was not identified within the umbilical cord. PMID- 2326238 TI - Regulation of protein synthesis in the first trimester human placenta by 17 beta oestradiol and progesterone. AB - Addition of 17 beta-oestradiol or progesterone to first trimester human placental explants in vitro resulted in the stimulation of protein synthesis, as seen by autofluorographic analysis of placental tissue and medium proteins. An increase in the incorporation of [35S]methionine into trichloroacetic acid-precipitable proteins was seen, following the addition of 17 beta-oestradiol. Use of aromatase inhibitor to block the synthesis of 17 beta-oestradiol inhibited the protein synthesis and while addition of cyclohexamide blocked both basal- and 17 beta oestradiol-induced protein synthesis, actinomycin-D blocked only 17 beta oestradiol induced protein synthesis. Double labelling of placental proteins in the presence and absence of 17 beta-oestradiol also indicated that there is a significant stimulation of protein synthesis by 17 beta-oestradiol. Based on these results it is suggested that oestradiol has a role in regulation of placental protein synthesis. PMID- 2326239 TI - Immunohistochemical demonstration of epidermal growth factor (EGF) receptors in normal human placental villi. AB - With an avidin-biotin-peroxidase (or glucose oxidase) complex method using anti epidermal growth factor receptor monoclonal antibody (528 IgG), the tissue and cellular distribution of the receptors for epidermal growth factors (EGF) in normal human placental villi, from 6 to 42 weeks of gestation, were studied. EGF receptors were mainly localized on the free surface of the syncytiotrophoblast that directly faced to intervillous space of the maternal circulation. The cell surface of cytotrophoblasts, except for the region that was adjacent to the basal lamina, was also positive for EGF receptors. The receptors were in close contact to the fetal vessels in the villous stroma. The EGF receptors on the syncytiotrophoblast were thought to be involved in the production and secretion of human chorionic gonadotropin and placental lactogen, probably under the control of maternal EGF. The receptors on cytotrophoblasts may play a role in trophoblastic proliferation, possibly mediated by EGF in the fetal circulatory system. PMID- 2326240 TI - Xenobiotic and steroid-metabolizing monooxygenases catalysed by cytochrome P450 and glutathione S-transferase conjugations in the human placenta and their relationships to maternal cigarette smoking. AB - Placentae from both smoking and non-smoking mothers were studied with respect to P450-dependent xenobiotic and steroid-metabolizing reactions, GSHt activity with different substrates and umbilical blood cotinine levels. Catalytic activities were determined in both freshly prepared homogenate subfractions and subfractions prepared after freezing the tissue sample. The results showed three correlation clusters: (i) AHH and ECDE (P less than 0.001), (ii) ECDE and ERDE (P less than 0.05), and (iii) Arom and CSCC reactions correlated with each other both in the mitochondria and microsomes. Among xenobiotic and steroid metabolizing activities, only CSCC and AHH showed a significant negative correlation. Our results agree with the earlier studies (Gottlieb and Manchester, 1986) reporting that xenobiotic metabolising MO and GSHt reactions did not show any statistically significant correlations, reflecting the fact that maternal cigarette smoking does not affect GSHt activities. However, in placentae from smoking mothers a statistically significant (P less than 0.01) positive correlation between GSHt and Arom activity was found. No plausible biological explanation is available for this finding. Among xenobiotic-metabolizing activities only ERDE correlated with plasma cotinine levels, suggesting that it is most closely related to the extent of maternal cigarette smoking. The present findings also suggest that cigarette smoke induced ERDE activity is a distinct one compared with the other xenobiotic metabolizing P450s. Negative correlations between xenobiotic-metabolizing MO activities and CSCC lend some support to an earlier suggestion (Juchau et al, 1972) that cigarette smoking affects endogenous steroid-metabolizing CSCC reaction catalyzed by P450. Whether this finding is a true biological phenomenon and what is the mechanism behind it remain to be elucidated. PMID- 2326241 TI - [Reports of tuberculosis of the respiratory organs in Stuttgart 1986-1988--an epidemiologic study]. AB - This retrospective study is based on 427 cases of pulmonary tuberculosis, 153 smear positive, 101 culture positive, and 173 without bacteriologic confirmation, children and cases of pleurisy excluded, all notified by the Public Health Department of Stuttgart in 1986-1988. Results are given by sex, age, nationality, cause of diagnosis, diagnosing institution, extent of disease, profession. These results are compared with those of former studies covering the periods 1964-1970 and 1980-1985. There is a remarkable statistically significant and continuous increase in the rates of passive case-finding. Unfortunately the rate of far advanced cases has significantly increased from 1964-1970 to 1986-1988, due to the smaller contribution of active case-finding, particularly the cessation of mass miniature X-ray examinations. Passive case-finding yields more advanced cases than active case-finding. But in spite of this fact there is no plea for intensifying active case-finding. As far advanced cases are more dangerous than others to their contacts the shift to passive case-finding has a negative impact on the general decline of tuberculosis. PMID- 2326242 TI - [Value of magnetic resonance tomography in Pancoast and other tumors with infiltration of the thoracic wall]. AB - Twenty-two patients with intrathoracic malignancies and suspected Pancoast and "break-out" tumours were submitted to a comparative investigation using CT scanning and MRI to detect infiltration of the chest-wall. In the patients, the lesion had been confirmed at surgery, which revealed malignant infiltration in 19 cases, and excluded in filtration in 3 cases. In 14 out of 19 patients, the CT scan revealed tumourous involvement of the chest-wall, while in five out of 19 patients, no such involvement was detected. Using MR imaging, tumour infiltration was detected in all 19 patients. A reliable MR sign of tumour involvement was the detection of signal-intensive lesions within the chest-wall in T1-weighted images following the administration of Gd-DTPA, and in the T2-weighted images. In contrast, signal enhancement of the pleura was found both in tumour involvement and in inflammation. In suspected tumorous chest-wall invasion MR imaging can demonstrate tumour involvement of the chest-wall when CT is equivocal. PMID- 2326243 TI - [Difficulties in the diagnosis of AIDS-associated intrapulmonary Kaposi sarcoma]. AB - Diagnosis of intrapulmonary Kaposi's sarcoma in HIV-infected patients may be extremely difficult. This is demonstrated in a case of a male patient with disseminated Kaposi's sarcoma and lethal pulmonary involvement. The value of various diagnostic procedures is discussed. PMID- 2326244 TI - [Detection of bronchial hyperreactivity using the 1-step histamine test]. AB - An attempt was made to establish whether patients with, and those without, bronchial hyperreactivity can be reliably differentiated on the basis of a single step histamine provocation test. Thirty-five asymptomatic persons (7 normal subjects, 13 patients with a history of coughing and oppressive sensation, and 13 patients with bronchial asthma) inhaled 10 breaths of a 5% histamine solution after a trial run with physiological NaCl solution. SGaw was determined in a volume constant body plethysmograph. The median dose of histamine was 0.51 mg, the sGaw median after inhalation was 0.37 kPa-1s-1. Between the values for sGaw prior to and following inhalation, and the histamine dose, a linear dose response curve was plotted, from which PD25sGaw was interpolated. On the basis of PD25sGaw, patients with bronchial hyperreactivity and normal subjects could be differentiated. At a PD25sGaw threshold value of 0.27 mg, the sensitivity is 0.85 and the specificity 0.86. Thus, the results obtained with single-step histamine provocation are comparable with those obtained with the conventional provocation methods involving increasing concentrations of histamine, and with those of the methacholine single-step provocation challenge. PMID- 2326245 TI - [Photodynamic therapy of bronchial cancer]. AB - Photodynamic therapy (PDT) with porphyrin derivatives (haematoporphyrin and dihaematoporphyrin ather/ester) and laser light of the wavelength 640 nm, is a new procedure for the treatment of carcinomas. This form of therapy is selective, can be applied through the bronchoscope, and is aimed at accomplishing curative elimination of central tumours of the lung. To date, we have successfully applied PDT in four selected patients. Our first patient was treated in April, 1987. The irradiation modalities and the clinical course are described. PMID- 2326247 TI - [Chylothorax in liver cirrhosis: a case report]. AB - In a patient with decompensated liver cirrhosis, ascites and hydrothorax on the right side, a chylous transformation of the peritoneal and pleural effusions was seen. This case prompts deliberations on the spontaneous chylothorax in a rather rare disease pattern, in respect of its connection with the abdomen and especially with the cirrhosis of the liver. PMID- 2326246 TI - [Atypical mycobacterioses: diseases caused by Mycobacterium malmoense]. AB - M. malmoense, once a rarity among the atypical mycobacterial infections, is presently being detected with ever greater frequency in human examination material. Strains of this organism apparently belong to the facultative pathogenic mycobacteria, as the cases described in this article show. Apart from other patients with mycobacterial infections of the lungs, the first case of infection of the lymph nodes in the neck is described. PMID- 2326248 TI - Serous carcinoma in endometrial polyps. AB - Sixteen patients who had serous carcinoma involving endometrial polyps and who demonstrated rare or absent myometrial or lymphovascular invasion are reported. Six of these patients had clinical manifestations of extrauterine disease at presentation. Of the ten patients who presented with clinical stage I disease, six eventually developed extrauterine recurrence, and four of these six were dead of disease within 19 mo of recurrence. Similarities between the patients who presented with extrauterine disease and the patients who presented with clinical stage I disease, including high percentages of patients with hyperplasia of ovarian epithelium surface and of fallopian tube epithelium, suggest that serous carcinoma involving endometrial polyps may represent one aspect of a multicentric disease. In such multicentricity, the entire female genital tract and the abdominal peritoneal surfaces would be at high risk for concurrent or subsequent involvement by serous carcinoma even in the absence of myometrial or lymphovascular invasion. PMID- 2326249 TI - Nucleolar organizer regions in seminoma and intratubular malignant germ cells. AB - Nucleolar organizer regions (NORs), as demonstrated by a silver-colloid staining technique, have been counted in 71 primary testicular seminomas (typical seminoma (TS) 31, high mitotic index seminoma (HMIS) 24, and spermatocytic seminoma (SS) 16) and ten seminomas metastatic to retroperitoneal lymph nodes. Mean NOR counts were 14.36 for TS; 17.66 for HMIS; 10.89 for SS; and 17.70 for metastatic seminoma. Analysis of data using Student's unpaired t-test showed a significant difference between the NOR counts obtained from TS, HMIS, and SS. Furthermore, there was a statistically significant difference between NOR counts in metastatic seminoma when compared with TS and SS but not HMIS. The association between tumor proliferation rates and intranuclear NOR numbers is discussed. In addition to a numerical variation, the NOR distribution throughout the nucleus was noted to be different in SS when compared with the other varieties of seminoma studied. The pattern observed had some features similar to those seen in cells of the spermatogenic series. The NOR technique was also applied to 19 cases of intratubular malignant germ cells (ITMGC). It was shown that these malignant cells were easily identified using this staining method and that the NOR distribution was similar to that seen in TS and HMIS. The mean NOR count in ITMGC was 16.41. This was significantly different from that of TS but not HMIS. PMID- 2326250 TI - Lupus membranous glomerulonephritis: different prognostic subgroups obscured by imprecise histologic classifications. AB - Eighteen patients with lupus membranous nephritis were retrospective identified by reviewing the renal biopsy records of an active renal pathology service. Seven had minimally proliferative membranous nephropathy (World Health Organization (WHO) classes Va and b). Eleven had membranous nephropathy with superimposed changes of focal or diffuse proliferative glomerulonephritis (WHO Vc and d). After mean follow-up periods of 73 +/- 6 and 74 +/- 15 mo, respectively, one patient of seven from WHO Va and b and seven of 11 from WHO Vc and d reached end stage renal disease. The latter patients were distinguishable from the former only by the degree of superimposed proliferation on renal biopsy and not by blood pressure, antinuclear antibody, anti-double stranded DNA, or complement levels. These data stand in contrast to the widely held belief that lupus membranous nephropathy is relatively benign. The belatedness of this observation is partially due to imprecision in nosology for patients with lupus who have renal biopsies with "overlap" characteristics. PMID- 2326251 TI - Tumor immunophenotype: comparison between primary neoplasm and its metastases. AB - Monoclonal antibodies (MAb) are firmly established diagnostic adjuvants both in vitro and in vivo. Their potential for immunotherapy is highly promising. Antigenic heterogeneity of cells within the same tumor is a well known phenomenon; however, no large-scale studies are available to ascertain to what degree metastases maintain the immunophenotype of the primary tumors. For that purpose, we studied 54 commonly epithelial malignancies using immunohistochemistry (IHC) with a panel of seven frequently used MAb recognizing a gamut of membrane and cytoplasmic antigens (AE-1, CAM 5.2, B72.3, MC10, anti carcinoembryonic antigen (anti-CEA), epithelial membrane antigen (EMA), and human milk fat globule (HMFG)). The number of metastases per primary tumor ranged between 1 and 26, with a total of 344 tissues studied. Metastases were located in regional and distal lymph nodes as well as in a diversity of organs (pancreas, adrenal, colon, spleen, soft tissues, etc). Only those cases in which all the tissues were obtained from a single surgical procedure and, therefore, uniformly fixed and processed, were selected. All the metastases from three cases (5.5%) were found to express one or two antigens not present on their primary. In no case did all metastases from a positive primary become negative for one MAb. Twelve cases (18.5%) showed modifications of the phenotype in one or more metastases. This study demonstrates that a broad phenotypic variation does not follow when tumors metastasize, and that it is, therefore, safe to foretell the metastatic immunophenotype based upon that of the primary tumor. PMID- 2326253 TI - A mutant T4 lysozyme (Val 131----Ala) designed to increase thermostability by the reduction of strain within an alpha-helix. AB - An attempt has been made to identify residues in T4 phage lysozyme that may have strained conformations and, by appropriate site-directed replacements, to reduce this strain and thus increase the thermostability of the protein. Valine 131, within alpha-helix 126-134, was identified as a potential candidate. Its side chain rotational angle, chi 1, differs by approximately 18 degrees from the low energy trans configuration. In addition, it is largely solvent exposed, yet is held in a rigid conformation. The mutant protein with Val 131 replaced by alanine was constructed and found to have a melting temperature 0.9 degrees C higher than that of wild-type lysozyme at pH 2.8. As a control, the mutant Val 131----Thr was also constructed and its melting temperature was found to be marginally lower than wild type. High-resolution crystal structure determinations of the mutant lysozymes show that their structures are virtually identical with that of wild type lysozyme, except for the Val----Ala or Val----Thr replacement. Analysis of the different structures suggests that the design of the Val----Ala substitution was, in principle, successful, although the apparent gain in stability caused by reduction in strain is modest and is somewhat offset by the loss of hydrophobic interactions and by entropic effects. The results also help to provide a structural rationalization for the experimental and empirical observations that alanine has a higher helix propensity than valine or threonine. PMID- 2326252 TI - Beta-lactamase of Bacillus licheniformis 749/C at 2 A resolution. AB - Two crystal forms (A and B) of the 29,500 Da Class A beta-lactamase (penicillinase) from Bacillus licheniformis 749/C have been examined crystallographically. The structure of B-form crystals has been solved to 2 A resolution, the starting model for which was a 3.5 A structure obtained from A form crystals. The beta-lactamase has an alpha + beta structure with 11 helices and 5 beta-strands seen also in a penicillin target DD-peptidase of Streptomyces R61. Atomic parameters of the two molecules in the asymmetric unit were refined by simulated annealing at 2.0 A resolution. The R factor is 0.208 for the 27,330 data greater than 3 sigma (F), with water molecules excluded from the model. The catalytic Ser-70 is at the N-terminus of a helix and is within hydrogen bonding distance of conserved Lys-73. Also interacting with the Lys-73 are Asn-132 and the conserved Glu-166, which is on a potentially flexible helix-containing loop. The structure suggests the binding of beta-lactam substrates is facilitated by interactions with Lys-234, Thr-235, and Ala-237 in a conserved beta-strand peptide, which is antiparallel to the beta-lactam's acylamido linkage; an exposed cavity near Asn-170 exists for acylamido substituents. The reactive double bond of clavulanate-type inhibitors may interact with Arg-244 on the fourth beta strand. A very similar binding site architecture is seen in the DD-peptidase. PMID- 2326254 TI - Hormonal regulation of potassium currents in single myometrial cells. AB - Three potassium currents (IK) were recorded from myometrial cells isolated from the uterus of rats at estrus and diestrus and kept in culture for 1-6 days. IK were differentiated by their modulation with norepinephrine and/or by their onset kinetics. At +50 mV the activation time constants were about 0.7 ms, 6 ms, and 15 ms for the fast, the intermediate, and the slow IK, respectively. Norepinephrine (1 microM) potentiated the fast IK and reduced the intermediate IK. In addition, differences were found with respect to cells from animals at estrus and diestrus. The fast IK was preferentially expressed in cultures from animals at estrus, whereas the intermediate IK was more frequent in cells from rats at diestrus. These results indicate that K+ channels from myometrial cells are multiregulated. Regulation may occur by short-term signals (neurotransmitters) and/or by preferentially expressing distinct types of channels depending on the hormonal status of the animal. PMID- 2326255 TI - Jet-propelled escape in the squid Loligo opalescens: concerted control by giant and non-giant motor axon pathways. AB - Recordings of stellar nerve activity were made during escape responses in living squid. Short-latency activation of the giant axons is triggered by light-flash stimulation that elicits a stereotyped startle-escape response and powerful jet. Many other types of stimuli produce a highly variable, delayed-escape response with strong jetting primarily controlled by a small axon motor pathway. In such cases, activation of the giant axons is not necessary for a vigorous escape jet. When they are utilized, the giant axons are not activated until well after the non-giant system initiates the escape response, and excitation is critically timed to boost the rise in intramantle pressure. Squid thus show at least two escape modes in which the giant axons can contribute in different ways to the control of a highly flexible behavior. PMID- 2326256 TI - Gene transfer by retrovirus-derived shuttle vectors in the generation of murine bispecific monoclonal antibodies. AB - The present study reports on the use of gene transfer by retrovirus-derived shuttle vectors in the generation of hybrid hybridomas secreting bispecific monoclonal antibodies. neo- and dhfr- genes were infected into distinct murine hybridomas, thus conferring a dominant resistance trait to geneticin (G418) and to methotrexate. The vectors employed were replication-deficient and dependent on complementation by a helper virus provided by the irradiated packaging lines. After cocultivation with the relevant packaging cell lines, stable hybridoma lines expressing the selectable markers were easily obtained and were then suitable for conventional somatic fusion. This high-efficiency method was used to generate two bispecific monoclonal antibodies simultaneously targeting molecules expressed on cytotoxic cells (i.e., T lymphocytes and natural killer cells) against a human melanoma-associated antigen. PMID- 2326257 TI - The polydeoxyadenylate tract of Alu repetitive elements is polymorphic in the human genome. AB - To identify DNA polymorphisms that are abundant in the human genome and are detectable by polymerase chain reaction amplification of genomic DNA, we tested the hypothesis that the polydeoxyadenylate tract of the Alu family of repetitive elements is polymorphic among human chromosomes. We analyzed the 3' ends of three specific Alu sequences and found that two (in the adenosine deaminase gene and the beta-globin pseudogene) were polymorphic. This novel class of polymorphisms, termed AluVpA [Alu variable poly(A)] may represent one of the most useful and informative group of DNA markers in the human genome. PMID- 2326258 TI - Early appearance and long-term persistence of the submicroscopic extrachromosomal elements (amplisomes) containing the amplified DHFR genes in human cell lines. AB - Submicroscopic extrachromosomal elements (amplisomes) containing amplified dihydrofolate reductase (DHFR) genes have been investigated in a methotrexate resistant derivative of the human cell line HeLa BU25, 10B3, by field-inversion gel electrophoresis. The amount and kinetics of formation of these elements have been correlated with the level and time course of overall DHFR gene amplification. The amplisomes account for the great majority and possibly the totality of the amplified DHFR genes in 10B3 cells. They appear very early during the development of methotrexate resistance and increase in parallel with the amplified genes. These observations suggest that these elements are involved in an early event, possibly the first event, of gene amplification in this system. Amplisomes tend to be lost from 10B3 cells in the absence of selective pressure, although much more slowly than expected from simple dilution of nonreplicating elements. Surprisingly, under selective pressure, these elements have shown no tendency to become integrated into chromosomes or to generate minute chromosomes over a period of almost 1 year, in contrast to what has been described in other systems. PMID- 2326259 TI - Multiple sites of action of volatile anesthetics in Caenorhabditis elegans. AB - The mechanism and site(s) of action of volatile anesthetics are unknown. In all organisms studied, volatile anesthetics adhere to the Meyer-Overton relationship- that is, a ln-ln plot of the oil-gas partition coefficients versus the potencies yields a straight line with a slope of -1. This relationship has led to two conclusions about the site of action of volatile anesthetics. (i) It has properties similar to the lipid used to determine the oil-gas partition coefficients. (ii) All volatile anesthetics cause anesthesia by affecting a single site. In Caenorhabditis elegans, we have identified two mutants with altered sensitivities to only some volatile anesthetics. These two mutants, unc 79 and unc-80, confer large increases in sensitivity to very lipid soluble agents but have little or no increases to other agents. In addition, a class of extragenic suppressor mutations exists that suppresses some altered sensitivities but specifically does not suppress the altered sensitivity to diethyl ether. There is much debate concerning the molecular nature of the site(s) of anesthetic action. One point of discussion is whether the site(s) consists of a purely lipid binding site or if protein is involved. The simplest explanation of our observations is that volatile anesthetics cause immobility in C. elegans by specifically interacting with multiple sites. This model is in turn more consistent with involvement of protein at the site(s) of action. PMID- 2326261 TI - Conversion of a 3-desoxysteroid to 3-desoxyestrogen by human placental aromatase. AB - Human placental aromatase is a cytochrome P-450 enzyme system which converts androgens to estrogens by three successive oxidative reactions. The first two steps have been shown to be hydroxylations at the androgen 19-carbon, but the third step remains unknown. A leading theory for the third step involves ferric peroxide attack on the 19-oxo group to produce a 19,19-hydroxyferric peroxide intermediate and subsequent collapse to estrogen. We had previously developed a nonenzymatic peroxide model reaction which was based on the above-mentioned theory, and we demonstrated the importance of 3-ketone enolization in facilitating aromatization. This study discusses the synthesis and nonenzymatic and enzymatic study of a 3-desoxy-2,4-diene-19-oxo androgen analogue. This compound was found to be a potent nonenzymatic model substrate and competitive inhibitor of aromatase (Ki = 73 nM). Furthermore, in an unprecedented event, this compound served as a substrate for aromatase, with conversion to the corresponding 3-desoxyestrogen. PMID- 2326260 TI - Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups. AB - Pulmonary surfactant contains two hydrophobic polypeptides, SP-B and SP-C, with known amino acid sequences and with truncated subforms lacking the N-terminal residues. Treatment of SP-C with KOH releases fatty acids (palmitic acid to more than 85%) in molar ratios of 1.8-2.0 relative to the polypeptide. Furthermore, plasma-desorption mass spectrometry shows native SP-C of both the intact and truncated types to be monomers with masses about 500 units higher than those expected for the polypeptide chains. After treatment with KOH, trimethylamine, or dithioerythritol, the polypeptide masses are obtained. These results prove that native SP-C is a lipopeptide with two palmitoyl groups covalently linked to the polypeptide chain. The deacylation conditions, the presence of two cysteine residues in the polypeptide, and the absence of other possible attachment sites establish that the palmitoyl groups are thioester-linked to the two adjacent cysteine residues. In contrast, the major form of porcine SP-B is a dimer without fatty acid components. That SP-C is a true lipopeptide with covalently bound palmitoyl groups suggests possibilities for functional interactions. It gives a direct physical link between SP-C and surfactant phospholipid components. Long chain acylation may constitute a means for association of proteins with membranes and could conceivably modulate the stability and biological activity of surfactant films. PMID- 2326262 TI - Calmodulin and calcium-dependent protease I coordinately regulate the interaction of fodrin with actin. AB - The calcium-dependent proteolysis of fodrin has been implicated in the regulation of secretion, neutrophil and platelet activation, and long-term potentiation in neurons. In vitro studies indicate that calcium-dependent protease I (calpain I) cleaves fodrin in the middle of the alpha subunit and in the COOH-terminal third of the beta subunit. Cleavage at the beta site requires calmodulin, which binds with high affinity to a single site in the alpha subunit. In vitro binding assays, nondenaturing gel electrophoresis, and velocity sedimentation identify a linkage between calcium-dependent protease I proteolysis of fodrin and the ability of calmodulin to regulate the self-association of fodrin and its interaction with actin. Three functional states appear to exist: (i) intact fodrin, which constitutively forms tetramers and binds F-actin; (ii) alpha cleaved fodrin, which loses its ability to self-associate and bind F-actin in the presence of calmodulin; and (iii) alpha,beta-cleaved fodrin, a form that is incompetent to establish tetramers or bind actin. Because actin binding and fodrin self-association occur at opposite ends of the molecule, whereas calmodulin binds at its center, these results indicate that long-range interactions exist within fodrin. They also offer an example of how two calcium dependent regulatory processes may act synergistically to reversibly regulate a linkage between the membrane and the cytoskeleton. PMID- 2326263 TI - Osteoinductive factor inhibits formation of human osteoclast-like cells. AB - Osteoinductive factor (OIF) is a glycoprotein in bone that induces ectopic bone formation. Implantation of OIF plus transforming growth factor beta (TGF-beta) type 1 or 2 into subcutaneous tissues of rats induces formation of bone at the implantation site. Since TGF-beta is also present in bone matrix and inhibits formation of multinucleated cells that express an osteoclast phenotype in long term human marrow cultures, we tested the effects of OIF on formation of these osteoclast-like cells to determine the effects of OIF on cells in the osteoclast lineage. We found that OIF inhibited total multinucleated cell (MNC) formation in a dose-dependent fashion and preferentially inhibited formation of MNCs that react with monoclonal antibody 23c6 (23c6-positive MNCs), an antibody that identifies osteoclasts. In addition, low concentrations of OIF in combination with low concentrations of TGF-beta acted synergistically to inhibit 23c6 positive MNC formation. The inhibition of 23c6-positive MNC formation by OIF was not mediated by prostaglandin synthesis. These data suggest that regulatory growth factors, such as OIF or TGF-beta, that are stored within the bone matrix and released when bone is resorbed can serve as natural inhibitors of osteoclast activity by inhibiting osteoclast formation. PMID- 2326264 TI - A glutathione conjugate of hepoxilin A3: formation and action in the rat central nervous system. AB - Incubation of (8R)- and (8S)-[1-14C]hepoxilin A3 [where hepoxilin A3 is 8-hydroxy 11,12-epoxyeicosa-(5Z,9E,14Z)-trienoic acid] and glutathione with homogenates of rat brain hippocampus resulted in a product that was identified as the (8R) and (8S) diastereomers of 11-glutathionyl hepoxilin A3 by reversed-phase high performance liquid chromatographic comparison with the authentic standard made by total synthesis. Identity was further confirmed by cleavage of the isolated product with gamma-glutamyltranspeptidase to yield the corresponding cysteinylglycinyl conjugate that was identical by reversed-phase high performance liquid chromatographic analysis with the enzymic cleavage product derived from the synthetic glutathionyl conjugate. The glutathionyl and cysteinylglycinyl conjugate are referred to as hepoxilin A3-C and hepoxilin A3-D, respectively, by analogy with the established leukotriene nomenclature. Formation of hepoxilin A3 C was greatly enhanced with a concomitant decrease in formation of the epoxide hydrolase product, trioxilin A3, when the epoxide hydrolase inhibitor trichloropropene oxide was added to the incubation mixture demonstrating the presence of a dual metabolic pathway in this tissue involving hepoxilin epoxide hydrolase and glutathione S-transferase processes. Hepoxilin A3-C was tested using intracellular electrophysiological techniques on hippocampal CA1 neurons and found to be active at concentrations as low as 16 nM in causing membrane hyperpolarization, enhanced amplitude and duration of the post-spike train afterhyperpolarization, a marked increase in the inhibitory postsynaptic potential, and a decrease in the spike threshold. These findings suggest that these products in the hepoxilin pathway of arachidonic acid metabolism formed by the rat brain may function as neuromodulators. PMID- 2326265 TI - Positive and negative regulatory elements of chicken vitellogenin II gene characterized by in vitro transcription competition assays in a homologous system. AB - A homologous in vitro transcription system was developed in which the cloned chicken vitellogenin II gene is faithfully transcribed by extracts prepared from chicken liver nuclei. The use of template deleted of its upstream region resulted in poor transcriptional efficiency, as did the use of extracts prepared from rooster liver, in which the gene is silent. The influence of individual cis elements was determined by transcription competition analysis. Oligonucleotides covering greater than 500 base pairs of the promoter region were used as competitor DNA in the in vitro reactions. Competition with an oligonucleotide covering part of the expression-specific DNase I hypersensitivity site B2, which contains a demethylation site, mCpG, at nucleotide position + 10, increased transcription of the gene, suggesting the binding of a repressor to this region. The enhancement of transcription was even more pronounced when the same oligonucleotide was methylated at the corresponding + 10 cytosine. Competition with oligonucleotides covering the TATA box, or the estrogen response element half-palindromic motif (GGTCA) at nucleotide positions -198 to -194, resulted in a large decrease in vitellogenin gene transcription, indicating that strongly activating factors bind to these regions. Competing oligonucleotides covering other GGTCA-containing motifs situated further upstream at nucleotide positions 292 to -288, -367 to -351, and -626 to -614 were increasingly less effective in inhibiting transcription. The results indicate that factors other than the estrogen receptor are involved in transcriptional activation of the vitellogenin II gene. PMID- 2326266 TI - Human trophoblast-extracellular matrix (ECM) interactions in vitro: ECM thickness modulates morphology and proteolytic activity. AB - Trophoblast invasion of the uterine extracellular matrix, a critical process for human implantation and uteroplacental vascular development, is a striking example of controlled invasiveness. To examine cellular behavior relevant to this process, human trophoblasts were cultured on (i) Millicell filters prelayered with Matrigel and (ii) coverslips precoated with a gentle slope of Matrigel (Matribeach). Histologic sections of the Millicell system demonstrated significant invasion. However, on Matribeach the cells exhibited markedly different characteristics depending on the thickness of the Matrigel. On zone 1 (1-4 microns thick), flat aggregates and syncytia were seen. In contrast, cells on zone 2 (4-14 microns) formed rounded aggregates with intercellular processes. In this zone, prominent degradation of pericellular Matrigel proteins was assessed by both light microscopy and scanning electron microscopy. Treatment with 8-bromo-cAMP inhibited this proteolytic process. On zone 3 (14-60 microns), unicellular trophoblasts or small aggregates caused minimal matrix degradation. JEG-3 human choriocarcinoma cells exhibited similar morphologic and degradative properties on Matribeach, but zone 2 proteolysis was not affected by 8-bromo cAMP. Our results suggest that extracellular matrix thickness has profound effects on cellular morphology and proteolytic activity. Furthermore, while both normal and malignant human trophoblasts can degrade extracellular matrix proteins, only normal trophoblast extracellular matrix degradation is inhibited by 8-bromo-cAMP. PMID- 2326267 TI - T-cell receptor gamma delta and gamma transgenic mice suggest a role of a gamma gene silencer in the generation of alpha beta T cells. AB - A T lymphocyte expresses on its surface one of two types of antigen receptor, T cell receptor alpha beta or T-cell receptor gamma delta, encoded by a pair of somatically rearranged alpha and beta or gamma and delta genes. It has been suggested that alpha beta T cells are generated only from precursor T cells that failed to rearrange gamma and delta genes in a functional form. However, we found that transgenic mice constructed with functionally rearranged gamma and delta genes produce a normal number of alpha beta T cells. The transgene gamma present in these alpha beta T cells is repressed apparently through an associated cis DNA element (silencer). We propose that some T-cell precursors are committed to generate alpha beta T cells independent of the rearrangement status of their gamma gene and that this commitment involves activation of a factor(s) that interacts with the gamma gene-associated silencer. PMID- 2326268 TI - Cerebellar degeneration-related antigen: a highly conserved neuroectodermal marker mapped to chromosomes X in human and mouse. AB - Cerebellar degeneration-related antigen (designated CDR34) was previously cloned by antibody screening of a cDNA library and was shown to be one of the target molecules recognized by autoantibodies in patients with paraneoplastic cerebellar degeneration. This molecule is distinctive in that it contains a tandem hexapeptide repetitive structure, presumably the basis for its high immunogenicity. In this study, we cloned the human CDR34 gene and proved that the entire repetitive sequence is encoded by a single exon without introns. We also showed that the nucleotide repeats are preserved only in the protein-coding sequences, suggesting evolutionary constraint in this region of the gene. Corresponding mouse cDNA clones were also isolated, which encoded a larger molecule with very similar hexapeptide repeating units. Comparison of the human and mouse repeats revealed a highly conserved Glu-Asp core in each unit, implicating the functional significance of this motif. Chromosomal mapping by somatic cell hybrid analysis mapped CDR34 to both human and mouse chromosomes X, and in situ hybridization further assigned CDR34 to human Xq24-q27. PMID- 2326269 TI - NMR detection of creatine kinase expressed in liver of transgenic mice: determination of free ADP levels. AB - To use the equilibrium established by creatine kinase (CK) to determine hepatic free ADP levels, the transcriptional control elements of the transthyretin gene were used to direct expression of the CK B isozyme to the livers of transgenic mice. Activities of CK ranging from 80-250 mumol per min per g (wet weight) were detected in liver extracts from five founder mice. The CK activity was stably transmitted to subsequent generations. Isozyme gels and immunoblots confirmed that the activity detected in extracts was due to the B isozyme of CK. Immunohistology indicated that the protein was expressed uniformly throughout the liver and was localized primarily to the cytoplasm. 31P NMR spectroscopy was used to detect the metabolic product of the CK reaction, phosphocreatine, demonstrating that the enzyme was active in vivo. The phosphocreatine level fell rapidly during anoxia (t1/2 = 1 min), indicating that the CK reaction was integrated into hepatic energy metabolism. The equilibrium established by CK was used to calculate a hepatic free ADP level of 0.059 +/- 0.004 mumol/g (wet weight). In vivo NMR studies of these mice will be valuable for studying the role of free ADP in regulating liver metabolism. PMID- 2326270 TI - Familial hypercholesterolemia in a rhesus monkey pedigree: molecular basis of low density lipoprotein receptor deficiency. AB - We have recently identified a family of rhesus monkeys with members exhibiting a spontaneous hypercholesterolemia associated with a low density lipoprotein receptor (LDLR) deficiency. By using the polymerase chain reaction, we now show that the affected monkeys are heterozygous for a nonsense mutation in exon 6 of the LDLR gene. This mutation changes the sequence of the codon for amino acid 284 (tryptophan) from TGG to TAG, thereby generating a nonsense codon potentially resulting in a truncated 283-amino acid protein, which needs documentation, however. This G----A mutation also creates a site for the restriction endonuclease Spe I. Using this site as a marker for this nonsense mutation, we have shown that the mutation is present in all of the affected members of the pedigree and absent in unaffected members and that the mutation segregates with the phenotype of spontaneous hypercholesterolemia through three generations. Quantitative analyses of RNA obtained from liver biopsies show that the abundance of the LDLR RNA is also reduced by about 50%. Thus, we have identified a primate model for human familial hypercholesterolemia which will be useful for studying the relationship between the LDLR and lipoprotein metabolism and for assessing the efficacy of diets and drugs in the treatment of human familial hypercholesterolemia. PMID- 2326271 TI - Normal diploid human and rodent cells lack a detectable frequency of gene amplification. AB - Gene amplification is frequently observed in tumors and transformed cell lines. This phenomenon is known to contribute to the generation of drug-resistant tumor cells and quantitation of the event is believed to have prognostic value in several types of neoplasias. To date, most studies of gene amplification have used immortalized cell lines and biopsied tumor samples. In this study I examine the amplification potentials of primary diploid cells, both human and rodent, and quantitatively compare them to the amplification potentials of their transformed counterparts. I have used a strictly defined protocol (i.e., selection at a stringency of 9 X LD50) to measure amplification potential at two loci, the gene for the multifunctional protein containing activities for carbamoyl phosphate synthase, aspartate transcarbamylase, and dihydroorotase (CAD) and the gene for dihydrofolate reductase (DHFR). I find that the frequency of amplification in transformed cells is at least four orders of magnitude greater than that in normal cells. Out of 29 cell populations studied, the 7 diploid normal cell populations exhibited no detectable amplification frequency (limit of detection at 10(-8) whereas the 22 transformed cell lines demonstrated amplification frequencies between 10(-3) and 10(-7). These results demonstrate that a dramatic difference exists between primary diploid cell populations and immortalized cell populations in their ability to amplify genomic sequences and suggests a significant difference in genetic stability between these two cell types. PMID- 2326272 TI - Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures. AB - Attention has focused on the cytokine interleukin 6 (IL-6) as a major mediator of acute-phase protein synthesis in hepatocytes in response to infection and tissue injury. We have evaluated the effects of IL-6 and IL-1 alpha as well as extracellular zinc and glucocorticoid hormone on metallothionein gene expression and cellular zinc accumulation in rat hepatocyte monolayer cultures. Further, we have evaluated the teleological basis for cytokine mediation by examining cytoprotection from CCl4-induced damage. Incubation of hepatocytes with IL-6 led to concentration-dependent and time-dependent increases in metallothionein-1 and 2 mRNA and metallothionein protein. The level of each was increased within 3 hr after the addition of IL-6 at 10 ng/ml (10 hepatocyte-stimulating factor units/ml). Maximal increases in metallothionein mRNA and metallothionein protein were achieved after 12 hr and 36 hr, respectively. In contrast, IL-1 alpha concentrations as high as 20 ng/ml (1000 lymphocyte-activating factor units/ml) had no effect. Concomitant with the up-regulation of metallothionein gene expression, IL-6 also increased cellular zinc. Responses to IL-6 required the synthetic glucocorticoid hormone dexamethasone and were optimized by increased extracellular zinc. In addition, IL-6 with dexamethasone, dexamethasone alone, and increased extracellular zinc each reversed, in decreasing potency, the deleterious effects of CCl4 on hepatocyte viability as measured by cell protein and lactate dehydrogenase activity of the medium. Thus, IL-6 is a major cytokine mediator of metallothionein gene expression and zinc metabolism in hepatocytes and provides cytoprotection from CCl4-induced hepatotoxicity via a mode consistent with dependence upon increased cellular metallothionein synthesis and zinc accumulation. PMID- 2326273 TI - Thermodynamic extent of counterion release upon binding oligolysines to single stranded nucleic acids. AB - A major contribution to the binding free energy associated with most protein nucleic acid complexes is the increase in entropy due to counterion release from the nucleic acid that results from electrostatic interactions. To examine this quantitatively, we have measured the thermodynamic extent of counterion release that results from the interaction between single-stranded homopolynucleotides and a series of oligolysines, possessing net charges z = 2-6, 8, and 10. This was accomplished by measuring the salt dependence of the intrinsic equilibrium binding constants--i.e., (delta log Kobs/delta log[K+])--over the range from 6 mM to 0.5 M potassium acetate. These data provide a rigorous test of linear polyelectrolyte theories that have been used to interpret the effects of changes in bulk salt concentration on protein-DNA binding equilibria, since single stranded nucleic acids have a lower axial charge density than duplex DNA. Upon binding to poly(U), the thermodynamic extent of counterion release per oligolysine charge, z, is 0.71 +/- 0.03, which is significantly less than unity and less than that measured upon binding duplex DNA. These results are most simply interpreted using the limiting law predictions of counterion condensation and cylindrical Poisson-Boltzmann theories, even at the high salt concentrations used in our experiments. Accurate estimates of the thermodynamic extent of counterion binding and release for model systems such as these facilitate our understanding of the energetics of protein-nucleic acid interactions. These data indicate that for simple oligovalent cations, the number of ionic interactions formed in a complex with a linear nucleic acid can be accurately estimated from a measure of the salt dependence of the equilibrium binding constant, if the thermodynamic extent of ion release is known. PMID- 2326274 TI - The t(10;14)(q24;q11) of T-cell acute lymphoblastic leukemia juxtaposes the delta T-cell receptor with TCL3, a conserved and activated locus at 10q24. AB - We cloned the t(10;14) recurrent translocation from CD3-negative T-cell acute lymphoblastic leukemia cells. The breakpoint at 14q11 involved an intermediate rearrangement of the delta T-cell receptor locus, suggesting that the translocation arose at the time of antigen receptor assemblage. Translocation introduced chromosome segment 10q24 as proven by hybridization of a breakpoint derived probe to flow-sorted chromosomes and metaphase chromosomes. Two t(10;14) breakpoints were clustered within a 600-base-pair region of 10q24 but no heptamer spacer-nonamer motifs resembling T-cell receptor/immunoglobulin rearrangement signals were noted at the breakpoint. A locus distinct from terminal deoxynucleotidyltransferase was found at 10q24. Evolutionarily conserved regions surrounding the 10q24 breakpoint were examined for transcriptional activity. A region telomeric to the 10q24 breakpoint, expected to translocate to the der(14) chromosome, recognized an abundant 2.9-kilobase RNA in a t(10;14) T-cell leukemia. This locus was not active in a variety of other normal and neoplastic T cells, arguing that it was deregulated by the introduction of the T-cell receptor. This locus is a candidate for a putative protooncogene, TCL3, involved in T-cell neoplasia. PMID- 2326275 TI - Constructing deletions with defined endpoints in Drosophila. AB - Chromosomes bearing small deletions are valuable tools in Drosophila genetics. We have investigated a method for efficiently constructing precise chromosomal deficiencies. Two P transposable elements were positioned within a progenitor strain at the sites of the desired deletion endpoints. Deletions spanning the two transposons were recovered at high frequency when P element transposase was expressed in these flies, but only if the flanking P elements were in a cis rather than a trans configuration. Appropriate progenitor strains can now be constructed to delete virtually any chromosomal region by utilizing an extensive collection of lines containing single P element insertions throughout the Drosophila genome. PMID- 2326276 TI - Vitamin B12S-promoted model rearrangement of methylmalonate to succinate is not a free radical reaction. AB - To probe for free radical intermediates in the model methylmalonate to succinate rearrangements promoted by vitamin B12s, a model series with a pentenyl side chain radical trap has been devised. The control free radical, generated by tri-n butyltin hydride treatment of bromomethyl-pentenylmalonate thioester, undergoes rapid cyclization to the six-membered ring, and, as anticipated, no succinate rearrangement product is detected. By contrast when the bromide is treated with vitamin B12s, little cyclized product is observed; the major product is the pentenyl succinate. This result demonstrates that the latter rearrangement does not follow a free radical pathway. PMID- 2326277 TI - Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro. AB - Three of 16 human monoclonal antibodies (hu-mAbs) enhanced human immunodeficiency virus type 1 (HIV-1) infection of MT-2 target cells by means of a mechanism that is dependent on complement. Enhanced infections are characterized by an increase in cytopathic effects and antigen synthesis as well as an increase in the production of progeny virus as detected by release of reverse transcriptase activity and infectious virus into the culture medium. Analyses by radioimmunoprecipitation, Western blot, and ELISA using the pENV9 envelope fragment localize the antigenic specificities of these three hu-mAbs to the N terminal two-thirds of the transmembrane protein gp41. Competitive binding experiments indicate that the hu-mAbs are reactive with immunodominant epitopes of gp41 recognized by sera from essentially all HIV-1-infected subjects. Combination dose-effect experiments demonstrate that these hu-mAbs can act synergistically in vitro to enhance HIV-1 infection. These data demonstrate that hu-mAbs directed against the HIV-1 transmembrane glycoprotein gp41 can enhance HIV-1 infection in vitro. The availability of these reagents allows for the mapping of enhancing epitopes on HIV-1 and provides a means for studying whether deletion of such enhancing epitopes from candidate HIV-1 vaccines might improve the protective immune response to HIV-1 in immunized humans and chimpanzees. PMID- 2326278 TI - Molybdopterin guanine dinucleotide: a modified form of molybdopterin identified in the molybdenum cofactor of dimethyl sulfoxide reductase from Rhodobacter sphaeroides forma specialis denitrificans. AB - The nature of molybdenum cofactor in the bacterial enzyme dimethyl sulfoxide reductase has been investigated by application of alkylation conditions that convert the molybdenum cofactor in chicken liver sulfite oxidase and milk xanthine oxidase to the stable, well-characterized derivative [di(carboxamidomethyl)]molybdopterin. The alkylated pterin obtained from dimethyl sulfoxide reductase was shown to be a modified form of alkylated molybdopterin with increased absorption in the 250-nm region of the spectrum and altered chromatographic behavior. The complex alkylated pterin was resolved into two components by treatment with nucleotide pyrophosphatase. These were identified as di(carboxamidomethyl)molybdopterin and GMP by their absorption spectra, coelution with standard compounds, and by further degradation by alkaline phosphatase to dephospho [di(carboxamidomethyl)]molybdopterin and guanosine. The GMP moiety was sensitive to periodate, identifying it as the 5' isomer. Chemical analysis of the intact alkylated pterin showed the presence of two phosphate residues per pterin. These results established that the pterin isolated from dimethyl sulfoxide reductase contains the phosphoric anhydride of molybdopterin and 5'-GMP, which is designated molybdopterin guanine dinucleotide. PMID- 2326279 TI - Substrate-, hormone-, and cAMP-regulated cytochrome P450 degradation. AB - The hepatic cytochrome P450 system, with numerous different P450 enzymes, is characterized by its inducibility by a variety of endogenous and exogenous compounds. Specific forms of P450, exhibiting distinct but partially overlapping substrate specificities, are increased in response to a given chemical. Consequently, the rate of elimination of the inducing compound is often enhanced and the system is in this respect adaptive to changes in the environment. Transcriptional activation mechanisms for the endo- or xenobiotically controlled P450 synthesis are well documented. Here we describe a mechanism for posttranslational ligand-dependent stabilization of ethanol-inducible P450IIE1 in hepatocyte cultures. Glucagon or 8-bromoadenosine 3',5'-cyclic monophosphate causes an enhanced rate of P450IIE1 degradation in the hepatocytes as well as phosphorylation on Ser-129, a reaction which denatures the protein under in vitro conditions. Substrates for the enzyme, such as ethanol and imidazole, protect the enzyme from phosphorylation and degradation in hepatocytes but do not influence phosphorylation or degradation of phenobarbital-inducible P450IIB1. Our proposed mechanism, which remains to be shown under in vivo conditions, describes the P450 molecules as receptors for the compounds in question and might provide a way by which endo- and xenobiotics regulate their own rate of metabolism. PMID- 2326280 TI - Different mouse mast cell populations express various combinations of at least six distinct mast cell serine proteases. AB - Mouse serosal mast cells (SMCs) and Kirsten sarcoma virus-immortalized mast cells store large amounts of mast cell carboxypeptidase A and serine proteases in their secretory granules. Secretory granule proteins from 2.6 x 10(6) purified SMCs were separated by NaDodSO4/PAGE, trans-blotted to poly(vinylidine difluoride) membranes, and subjected to amino-terminal amino acid sequencing. Four distinct mast cell serine proteases were identified. With mast cell carboxypeptidase A, these serine proteases comprise the major proteins of mouse SMC secretory granules. Each of the four SMC serine proteases was distinct from the two serine proteases present in mucosal mast cells in the intestines of helminth-infected mice. The secretory granules of a Kirsten sarcoma virus-immortalized mast cell line contained three of the SMC-derived serine proteases and one of the mucosal mast cell-derived serine proteases. Thus, the family of mouse mast cell secretory granule serine proteases has at least six distinct members that can be expressed in different combinations in different mast cell populations. PMID- 2326281 TI - Protein model structure evaluation using the solvation free energy of folding. AB - A systematic study of solvation free energy of folding for proteins with known crystallographic structures is presented. There is a linear relationship between the solvation free energy of folding and the protein size. This relationship, which can be rationalized by a simple model of chain folding, allows prediction of the solvation free energy of folding for proteins for which no high resolution structures are available. All misfolded structures analyzed show solvation free energies higher than predicted; however, some of the misfolded structures have values close enough to the predicted values so that one must be very careful when using such a criterion to check the correctness of a protein model. PMID- 2326283 TI - Intestinal calcium transport in spontaneously hypertensive rats (SHR) and their genetically matched WKY rats. AB - Calcium transport across the basolateral membranes of the enterocyte represents the active step in calcium translocation. This step occurs by two mechanisms, an ATP-dependent pump and a Ca2+/Na+ exchange process. These studies were designed to investigate these two processes in jejunal basolateral membrane vesicles (BLMV) of the spontaneously hypertensive rats (SHR) and their genetically matched controls, Wistar-Kyoto (WKY) rats. The ATP-dependent calcium uptake was stimulated several-fold compared with no ATP condition in both SHR and WKY, but no differences were noted between rate of calcium uptake in SHR and WKY. Kinetics of ATP-dependent calcium uptake at concentrations between 0.01 and 1.0 microM revealed a Vmax of 0.67 +/- 0.03 nmol/mg protein/20 sec and a Km of 0.2 +/- 0.03 microM in SHR and Vmax of 0.69 +/- 0.12 and a Km of 0.32 +/- 0.14 microM in WKY rats. Ca2+/Na+ exchange in jejunal BLMV of SHR and WKY was investigated in two ways. First, sodium was added to the incubation medium (cis-Na+). Second, Ca2+ efflux from BLMV was studied in the presence of extravesicular Na+ (trans-Na+). Both studies suggest a decreased exchange of calcium and Na+. Kinetic parameters of Na(+)-dependent Ca2+ uptake at concentrations between 0.01 and 1.0 microM exhibited Vmax of 0.05 +/- 0.01 nanmol/mg protein/5 sec and a Km of 0.21 +/- 0.13 microM in SHR and Vmax of 0.11 +/- 0.02 nanmol/mg protein/5 sec and a Km of 0.09 +/- 0.05 in WKY, respectively. These results confirm that the intestinal BLMV of SHR and WKY rats have two mechanisms for calcium extrusion, an ATP-dependent Ca2+ transport process and a Na+/Ca2+ exchange process. The ATP-dependent process appears to be functional in SHR; however, the Ca2+/Na+ exchange mechanism appears to have a marked decrease in its maximal capacity. These findings suggest that calcium extrusion via Ca2+/Na+ is impaired in the SHR, which may lead to an increase in intracellular calcium concentration. These findings may have relevance to the development of hypertension. PMID- 2326284 TI - Influence of coffee on fluoride metabolism in rats. AB - Concomitant intragastric administration of sodium fluoride and coffee resulted in a significantly higher (P less than 0.01) plasma fluoride level than intake of the same amount of fluoride with water. The same result was obtained when coffee was substituted with an equivalent amount of caffeine. Comparison of plasma fluoride levels by total area under the curve of plasma fluoride concentration versus time indicated an almost 2-fold difference. Although the mechanism(s) is not known, it appears that caffeine is responsible for the present observation. This finding could help explain the variations in the incidence of dental fluorosis among people living in optimally fluoridated communities. PMID- 2326282 TI - Glucose transporters serve as water channels. AB - Water traverses the plasma membranes of some eukaryotic cells faster than can be explained by the water permeability of their lipid bilayers. This has led to a search for a water channel. Our previous work identified glucose transporters as candidates for such a channel. We report here that Xenopus laevis oocytes injected with mRNA encoding the brain/Hep G2, adult skeletal muscle/adipocyte, or liver forms of the glucose transporter exhibit an osmotic water permeability of their plasma membranes larger than that of untreated oocytes. The osmotic water permeability component attributable to glucose transporters increased an average of 4.8-fold in the injected oocytes. These studies provide direct evidence that the facilitative, sodium-independent mammalian glucose transporters serve as membrane water channels. PMID- 2326285 TI - Lack of effect of propylthiouracil and methylmercaptoimidazole on thyroglobulin biosynthesis. AB - Experiments were performed both in vivo and in vitro to test a previous proposal that part of the antithyroid action of the thioureylene drugs, propylthiouracil (PTU) and methylmercaptoimidazole, can be attributed to inhibition of thyroglobulin (Tg) biosynthesis. Rat thyroid lobes were incubated in leucine-free Eagle's medium containing bovine thyroid-stimulating hormone and 0, 0.1-0.2, or 1 mM drug. After a 30-min preincubation, 5 mu Ci of [14C]leucine were added and the incubation was continued for 4 hr. The soluble fraction was analyzed by sucrose density gradient centrifugation, and the fractions corresponding to the 19S Tg peak were pooled and assayed for 14C. No inhibition of 14C incorporation into 19S Tg was observed, even in thyroid lobes incubated in the presence of 1 mM methylmercaptoimidazole or 2 mM PTU. At the same time, 14C incorporation into 19S Tg was completely inhibited when lobes were incubated in the presence of 0.1 mM puromycin. In vivo, rats received an injection of PTU (1 mumol/100 g body wt), followed 60 min later by an injection of 25 mu Ci of [14C]leucine. Blood samples and thyroids were taken 5 hr after the [14C]leucine injection. Serum thyroid stimulating hormone was not significantly affected by the PTU injection. The thyroid-soluble fraction was analyzed by sucrose density gradient centrifugation. No significant differences between saline and PTU-injected groups were observed in [14C]leucine incorporation into 19S Tg. We conclude from both our in vitro and our in vivo studies that PTU and methylmercaptoimidazole have no inhibitory effect on thyroglobulin synthesis in rat thyroids and that such inhibition does not play a significant role in the antithyroid action of these drugs. PMID- 2326286 TI - Danazol suppression of luteinizing hormone in the rat: evidence for mediation by both androgen and estrogen receptors. AB - Previous studies had indicated that the effects of danazol on rat peripheral tissues were mediated through both androgen and estrogen receptors. The purpose of this study was to examine the role of androgen and estrogen receptors in danazol suppression of luteinizing hormone (LH) in the rat. The estrogen receptor antagonist, LY 156758, partially antagonized the suppressed levels of LH observed 3-5 hr after administration of danazol to ovariectomized rats. In contrast, the androgen receptor antagonist, flutamide, had no effect on suppressed LH levels 3 5 hr after danazol, but did partially reverse the inhibition of LH 24 hr after danazol administration to ovariectomized rats. Danazol also increased pituitary progesterone receptor levels, an estrogen-sensitive end point. These data indicate that the suppressed levels of LH following danazol treatment resulted from the functional activation of both androgen and estrogen receptors. PMID- 2326287 TI - Evidence for maternal regulation of progesterone production at midpregnancy in the mouse. AB - Mice with major differences in embryo survival and progesterone secretion were used to study the relative roles of maternal and embryonic genotype in the control of progesterone production at midpregnancy. Reciprocal transfer of embryos from strains with high (Line S1) or low (Line G) embryo survival resulted in progesterone concentrations consistent with maternal genotype in females carrying the same number of fetuses. This suggests that maternal rather than fetal gene expression determines the setpoint for progesterone production during the period of transition from maternal to fetal-placental control of ovarian steroidogenesis. PMID- 2326288 TI - Fatty acid oxidation. Clinical, biochemical and molecular aspects. Proceedings of the international symposium. Philadelphia, November 6-9, 1988. PMID- 2326289 TI - Regulation of electron transfer to general acyl-CoA dehydrogenase by substrate binding. PMID- 2326290 TI - Functional studies on general acyl-CoA dehydrogenase using chromophoric substrates. PMID- 2326291 TI - Mechanisms of enzyme inhibition by hypoglycin, methylenecyclopropylglycine and their metabolites. PMID- 2326292 TI - Mechanisms of dicarboxylic aciduria and dicarboxylic acid metabolism. PMID- 2326293 TI - Epimerization of 3-hydroxyacyl-CoA esters as an auxiliary reaction in the beta oxidation of unsaturated fatty acids. PMID- 2326294 TI - Isovaleric acidemia: personal history, clinical survey and study of the molecular basis. PMID- 2326295 TI - The long-chain acyl-CoA dehydrogenase deficiency. PMID- 2326296 TI - Short-chain acyl-CoA dehydrogenase deficiency. PMID- 2326297 TI - Short-chain and medium-chain acylCoA dehydrogenases are lowered in riboflavin responsive lipid myopathies with multiple acylCoA dehydrogenase deficiency. PMID- 2326298 TI - Genetic defects of acyl-CoA dehydrogenases: studies using an electron transfer flavoprotein reduction assay. PMID- 2326299 TI - Fatty acid oxidation defects as causes of unexpected death in infancy. PMID- 2326300 TI - Purification and characterization of five acyl-CoA dehydrogenases from rat liver mitochondria. PMID- 2326301 TI - Acylcarnitines in the urine of a patient with medium chain acyl-CoA dehydrogenase (MCAD) deficiency and in normal children. PMID- 2326302 TI - Diagnosis of medium chain acyl-CoA dehydrogenase deficiency by stable isotope dilution analysis of urinary acylglycines: retrospective and prospective studies, and comparison of its accuracy to acylcarnitine identification by FAB/mass spectrometry. AB - In summary, we have demonstrated that the accurate quantitation of urinary HG and PPG by stable isotope dilution analysis is currently the most reliable method for the diagnosis of MCAD deficiency. This method is particularly useful for testing random samples from asymptomatic patients without any provocative test, and it is suitable to widely survey a fairly large population, such as patients with episodic manifestations and families with a history of SIDS. PMID- 2326303 TI - The fate of orally ingested 3-phenylpropionic acid. PMID- 2326304 TI - A murine model for short-chain acyl-CoA dehydrogenase deficiency. PMID- 2326305 TI - Hepatic and muscular forms of palmitoyl carnitine transferase deficiency. PMID- 2326306 TI - A genetic defect in carnitine transport causing primary carnitine deficiency. PMID- 2326307 TI - Clinical and biochemical aspects of glutaric acidemia type II. PMID- 2326308 TI - Clinical and biochemical presentations in 20 cases of hydroxydicarboxylic aciduria. PMID- 2326309 TI - The L-3-hydroxyacyl-CoA dehydrogenase deficiency. PMID- 2326310 TI - In vitro translation, mitochondrial uptake and post-translational processing of four acyl-CoA dehydrogenases. PMID- 2326311 TI - Inborn errors of peroxisomal beta-oxidation: biochemical identification using enzymic and immunological methods. PMID- 2326312 TI - Structural studies of medium-chain acyl-CoA dehydrogenase from pig liver mitochondria. PMID- 2326313 TI - The acyl-CoA dehydrogenase family: homology and divergence of primary sequence of four acyl-CoA dehydrogenases, and consideration of their functional significance. PMID- 2326314 TI - The tissue-specific and developmental regulation of expression of rat medium chain acyl-CoA dehydrogenase mRNA. PMID- 2326315 TI - Molecular analysis of medium chain acyl-CoA dehydrogenase deficiency. PMID- 2326316 TI - Molecular cloning and nucleotide sequence of cDNAs encoding human short chain acyl-CoA dehydrogenase and study of the molecular basis of human short chain acyl CoA dehydrogenase deficiency. PMID- 2326317 TI - Molecular cloning and nucleotide sequence of cDNA encoding the rat long chain acyl-CoA dehydrogenase precursor. PMID- 2326318 TI - Biosynthesis, molecular cloning and sequencing of electron transfer flavoprotein. PMID- 2326319 TI - Progress in cloning the gene for electron transfer flavoprotein:ubiquinone oxidoreductase. PMID- 2326320 TI - Molecular cloning of the cDNA for rat mitochondrial enoyl-CoA hydratase. PMID- 2326321 TI - Biosynthesis and mitochondrial import of fatty acid oxidation enzymes. PMID- 2326322 TI - Molecular cloning and sequencing of the peroxisomal beta-oxidation enzymes. PMID- 2326323 TI - Dynamic interactions of myelin proteins. Proceedings of a symposium. Chicago, Illinois, April 5-10, 1989. PMID- 2326324 TI - Sensory systems and nipple attachment behavior in neonatal pigs. AB - The influence of piglet sensory systems and the role of odors from the sow's ventrum on piglet nipple attachment were investigated. In Experiment 1, four sows had their ventrum washed with organic solvents and four were unwashed control sows. Piglets were given one of four treatments shortly after birth: nares that were mechanically blocked (B), a lidocaine flush of the olfactory system (LFO), a saline flush of the olfactory system (SFO) or nontreated controls (C). Time to attach to a nipple, up to a maximum of 600 sec, was recorded. On unwashed sows, nipple attachment was affected (p less than 0.01) by piglet treatment. Piglets have B or LFO treatments took longer to attach to a nipple than SFO or C piglets. Piglets of all treatments took longer to attach to washed sows than to unwashed controls. Seven unwashed sows and their litters were used in Experiment 2. Piglets were tested after birth with one of the following treatments: an olfactory system flushed with lidocaine, lidocaine on nose (LN), lidocaine applied to the tongue (LT) or nontreated controls. All lidocaine-treated piglets took more time to attach than C piglets. Nipple attachment latencies were intermediate for LN or LT piglets. In Experiment 3, three unwashed sows and their litters were used. Treatments were: lidocaine applied to both the nose and the tongue (LNT), an olfactory system flushed with lidocaine or nontreated controls. LFO piglets had an increased latency to attachment compared to controls while LNT piglets were intermediate in latency to attach. Piglet olfaction, gustation and tactile sensory modalities as well as odors on the sow's ventrum influenced nipple attachment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326325 TI - Sex differences in aversive and appetitive conditioning in two strains of rats. AB - In order to examine sex differences in non sexual behavior, 40 rats of each sex from two strains (gray, A x C and albino, Sprague-Dawley) were trained, using different experimental procedures. In Experiment I, aversive conditioning in a one-way (easy task) and a two-way (difficult task) active avoidance task was examined. Results consistently showed that males of both strains were inferior to females in the acquisition of the two-way avoidance task. A significant interaction between sex of both strains and the difficulty of the task was found. In Experiment II, rats were trained in a Sutherland Apparatus in an easy (black vs. white) and a difficult (horizontal vs. vertical) visual discrimination task, using appetitive reinforcement; no differences between sexes were observed. A significant interaction, however, was found between strain and task, indicating a lower performance of the A x C strain in the difficult task. The results are discussed within the theoretical framework of the Yerkes-Dodson Law, which states a relationship between drive level, performance and different degrees of task difficulty. PMID- 2326326 TI - The neural control of cyclic motor activity in the fetal rat (Rattus norvegicus). AB - The spontaneous behavior of rat fetuses (in a saline bath with fetal-placental uterine connections intact) was observed directly for 30 minutes on Day 20 of gestation. Rearleg and nonrearleg movements from fetuses with a mid-thoracic spinal cord transection or sham operation were analyzed for cyclic organization. Oscillations in rearleg activity occurred at the same frequency in fetuses with spinal cord transections (0.74 cycle/min) and sham-operated fetuses (0.72 cycle/min). However, oscillations in nonrearleg activity were much slower in the fetuses with spinal cord transections (0.30 vs. 0.77 cycle/min). Other characteristics of the cyclic patterns in motor activity were unaffected. The findings demonstrate 1) the caudal half of the spinal cord can generate cyclic output in the absence of descending input from the brain, 2) there is no single timing center, and 3) rostral sources are slower. PMID- 2326327 TI - Cholinergic regulation of sexual behavior in female hamsters. AB - The effect of cholinergic manipulations on sexual behavior in female hamsters was determined in a series of experiments. The cholinergic receptor antagonist, scopolamine, reduced total lordosis duration following systemic (1 mg/kg) or intraventricular (10 and 20 micrograms bilaterally) administration to ovariectomized hamsters primed with estrogen and progesterone. The inhibitory effect of scopolamine on lordosis occurred within 15 min after either treatment route and persisted at 2 hr after systemic administration. Intraventricular administration of the acetylcholinesterase inhibitor, physostigmine (10 micrograms bilaterally), activated lordosis of short duration in ovariectomized hamsters primed only with estrogen. These results indicate that the cholinergic system plays a facilitative role in the regulation of sexual behavior in female hamsters similar to that demonstrated previously in female rats. The activational effect of cholinergic neurotransmission on female sexual behavior may be a neural mechanism common to a number of mammalian species. PMID- 2326328 TI - Dam strain affects cardiovascular reactivity to acute stress in BHR. AB - The effect of maternal strain on reactivity to acute stress was studied in F1 reciprocals produced by crossing the spontaneously hypertensive rat (SHR) with its normotensive progenitor, the Wistar-Kyoto (WKY). This F1 generation, known as the borderline hypertensive rat (BHR), is genetically predisposed to develop hypertension in response to chronic stress or high dietary sodium. Reciprocals, considered to be genetically equivalent aside from sex-linked traits, differ in strain of dam during intrauterine and preweanling development. At 17 weeks of age, reciprocal F1 males did not differ in open-field behavior (squares crossed, rearings, and defecation measured over 3 days in 15-min sessions) or in home-cage measurements of mean arterial pressure (MAP) and heart rate (HR). However, different patterns of cardiovascular reactivity were displayed to transfer and footshock. While WKY-mothered rats reacted with graded pressor responses, SHR mothered rats responded maximally to transfer, showed no additional increase to footshock, and maintained peak responding after footshock was terminated. Such reactivity differences may mediate the impact of environmental variables on the genetic disposition to hypertension. PMID- 2326329 TI - Effects of the CCK receptor antagonist MK-329 on food intake in pigs. AB - The cholecystokinin (CCK) receptor antagonist MK-329 (previously L364,718) was administered intravenously (IV) (17.5-140 micrograms/kg) to pigs trained to make operant responses for food reinforcements after 4 hr of food deprivation. MK-329 produced a dose-related increase in food intake during the 2-hr test period, with maximum increases occurring at a dose of 70 micrograms/kg. CCK (1 micrograms/kg IV) produced a short-term reduction in feeding and this effect was completely abolished by pretreating the animals with MK-329 (70 micrograms/kg). The present results lend support to the hypothesis that endogenous CCK is involved in satiety. PMID- 2326330 TI - Predictability of repeated challenge: effects on cardiovascular activity in the type A (coronary prone) behavior pattern. AB - Fifty-two healthy young adults classified either as Type A (coronary prone) or Type B were randomly assigned to a vigilance task during which observing responses produced targets according to either a predictable (i.e., fixed interval 90-sec) or a nonpredictable (i.e., random-interval 90-sec) reinforcement schedule. During the task, blood volume pulse, interbeat interval, masseter (EMG) activity, and blood pressure were monitored. Transient peripheral vasomotor constriction and heart rate increases were initiated within an 8- to 12-sec period following target detection with the predictable schedule, with subjects evincing greater responsivity than their nonpredictable schedule counterparts. Type A subjects assigned to the random-schedule evinced significantly shorter heart rate and blood volume pulse response durations than did Type B subjects. Longer postevent EMG elevations were evidenced by subjects assigned to the predictable schedule. No significant blood pressure differences were found among the groups. The impact of challenge-contingent behavior on cardiovascular responsivity and the relevance of attentional processes to this relationship and to cardiovascular risk are discussed. PMID- 2326331 TI - The significance of decreased ambulatory activity during the generation by long term observation of obesity in ovariectomized rats. AB - We attempted to determine the significance of ambulatory activity as a cause of overweight in ovariectomized rats. Drinking and ambulation were measured continuously and directly for periods up to 12 months in special apparatus developed at Gunma University. In older rats, ambulatory activity decreased much more in the ovariectomy group than in the control group. There was no difference in food intake between the ovariectomized and the control group. After 2 months, the ovariectomy group increased body weight more than the control group despite no difference in food intake. The decrease in ambulatory activity was consistent in the ovariectomy group, regardless of any differences in age and body weight. These results indicate that decrease of energy expenditure by gradual decrease in ambulatory activity may be an important factor as a cause of overweight in ovariectomized, obese rats. PMID- 2326332 TI - Social status and nerve growth factor serum levels after agonistic encounters in mice. AB - Ten repeated daily interactions (20 min each) of the same pairs of isolated male mice produced a clear distinction between attacking (dominant) and defeated (subordinate) animals. The fighting level remained fairly constant over the 10 days. One hr after the end of the 10th session, the increase in serum NGF levels described previously (2) was significantly more marked in subordinate than in dominant mice. The mean level of serum NGF was correlated with the number of fighting episodes, particularly in the case of dominant individuals. Moreover, within-pair differences in NGF values were correlated with differences in locomotor activity between dominants and subordinates; this makes it possible that stimuli other than those produced by fighting per se may be responsible for the increase in circulating NGF. As is well known, the adrenal hypertrophy produced by fighting stress is more marked in subordinate than in dominant mice, while previous work has shown that stress of a nonpsychosocial kind does not elevate serum NGF levels. Therefore, the present data support the hypothesis that NGF release contributes to the modulation of adrenal function in a situation specific fashion. PMID- 2326333 TI - Central effect of yohimbine on sexual behavior in the rat. AB - A large range of doses of yohimbine (Y) was administered intracerebroventricularly (ICV) (5-100 micrograms/rat) or intraperitoneally (IP) (0.35-10 mg/kg) to male rats and the effects on sexual, locomotor and general behavior were evaluated. For both routes there was a clear-cut inverted-U effect (stimulating/depressing), calculable as parabolic regressions on the log of administered doses. The maximal stimulating doses (15 micrograms/rat ICV and 1 mg/kg IP) significantly shortened mount, intromission and ejaculation latencies and the mean interintromission interval. These data indicate the importance of CNS mechanisms in the sexual effect of Y. PMID- 2326334 TI - Hippocampal electrical activity during social interactions in rabbits living in a seminatural environment. AB - The aim of the present experiment was to study the effect on the electrical activity of the hippocampus of interactions between male rabbits. The behavioral and electrical correlates of social interactions were studied in 13 animals living in a seminatural environment. Rabbits carrying chronic microelectrodes implanted in the hippocampus were introduced singly into a large, natural open air enclosure and their spontaneous behavior observed until they had adapted to the environment. Hippocampal EEG was recorded by telemetry. Subsequently, a second rabbit (intruder) was introduced into the enclosure. Hippocampal EEG and the concomitant behavior of the resident were stored and analyzed. Alerting reactions, approaching and conflictual elements were characterized by typical electrical patterns and parameters. Power spectra of hippocampal EEG showed a significant increase in frequency passing progressively from environment-related behaviors to more specific elements directed towards the intruder. Behavioral elements belonging to the same modality, such as running, chase and flight had different hippocampal EEG frequency distributions. Seven residents showed a clear prevalence of offensive reactions (offensive rabbits) and six defensive elements (defensive rabbits). Defensive animals showed very high frequency levels during nose and flight. Exploration of offensive rabbits in the period preceding and following the introduction of the intruder was characterized by higher EEG frequency values than exploration of defensive animals. PMID- 2326335 TI - Hypothalamic effects on medullary reticular activation of deep back muscle EMG. AB - Medullary reticular stimulation can activate deep back muscle EMG in urethane anesthetized female rats. Midbrain central gray stimulation can facilitate brainstem reticular control over deep back muscles. Since these deep back muscles lateral longissimus (LL) and medial longissimus (ML) execute the vertebral dorsiflexion of lordosis behavior, and since the motor control hierarchy sketched above parallels lordosis behavior circuitry, we tested the hypothesis that medial hypothalamic lesions (which, in behavioral experiments, decrease lordosis) can also reduce medullary reticular activation of deep back muscle EMG. Urethane anesthetized rats were tested systematically for amplitude of lateral longissimus (LL) and medial longissimus (ML) EMG responses to electrical stimulus trains applied to the nucleus gigantocellularis (NGC) of the medullary reticular formation, before and after electrolytic lesions of the ventromedial hypothalamus (n = 18) or control sites (n = 30). Bilateral ventromedial hypothalamic lesions were able to greatly reduce EMG responses in LL and ML, often with a time course similar to previous lordosis behavioral results. Surprisingly, lesions at the anterior ventromedial nucleus pole were particularly effective, and may reflect importance of intraventromedial local neurons. Although, on the average, various control lesions were less effective, the ventromedial hypothalamic effect was not unique. For example, it was possible to see an EMG decrease following lesions of the dorsomedial thalamus. Nevertheless, EMG loss was not well correlated with changes in the cortical EEG, and thus does not appear to be a simple consequence of changes in "arousal." In conclusion, it appears that ventromedial hypothalamic neurons can affect medullary reticular control of back muscle EMG, but must share this role with other forebrain elements. PMID- 2326336 TI - Effect of an endogenous satiety substance, 2-buten-4-olide, on gastric acid secretion and experimental ulceration in rats. AB - The involvement of a feeding-related endogenous sugar acid, 2-buten-4-olide (2 B4O) on central regulation of gastric acid secretion, and its antiulcer effects on several gastric and duodenal experimental ulcer models were investigated in rats. Spontaneous gastric acid secretion was not affected by 2-B4O at doses below 10 mg/kg. The peripheral secretagogue-stimulated gastric secretions were significantly increased by pretreatment with 2-B4O. Gastric acid secretion induced by 2-deoxy-D-glucose (2-DG) was significantly suppressed by pretreatment with 2-B4O at doses between 0.1 and 100 mg/kg. Gastric and duodenal ulcerations induced by cold stress plus indomethacin, restraint and water immersion stress, pylorus ligation or cysteamine were also inhibited by pretreatment with 2-B4O. The results suggest that antiulcer effects of 2-B4O are due to suppression of gastric acid secretion via reduction of activity of the vagus nerve and gastric related hypothalamic neurons. Thus, 2-B4O may be useful for treatment of gastroduodenal ulcer. PMID- 2326337 TI - Frontal cortex as the site of action of physostigmine in nbM-lesioned rats. AB - The administration of a variety of cholinomimetic agents to nucleus basalis of Meynert-lesioned rats has been shown to alleviate their lesion-induced memory deficits. This experiment attempted to determine whether the frontal cortex was the site of the memory enhancing action of the cholinomimetic physostigmine. Different groups of rats received excitotoxic lesions of the basal forebrain, the frontal cortex or both. Immediately after one trial passive avoidance training, these rats were injected with either saline or a 0.06 mg/kg dose of physostigmine. Physostigmine enhanced the 72-hour retention test performance of sham-operated and basal forebrain-lesioned rats, but failed to affect the performance of rats with cortical lesions. These data were interpreted as consistent with the hypothesis that the memory-enhancing effects of physostigmine are at least partially mediated by the frontal cortex. PMID- 2326338 TI - Parietal cortex lesions do not impair retention performance of rats in a 14-unit T-maze unless hippocampal damage is present. AB - Young male F-344 rats, pretrained in a straight runway to avoid shock, were then trained in a shock-motivated 14-unit T-maze. One day after maze acquisition, extensive parietal cortex lesions (PC) or sham operations (CON) were performed to assess possible involvement of parietal cortex in the age-related impairment previously observed in this task. Twelve days after surgery, a first 10-trial retention session in the 14-unit T-maze was conducted. One day later the vibrissae of half the rats in each group were clipped to examine involvement of the damaged barrel cortex field in maze performance of rats with PC lesions. The following day a second 10-trial retention session occurred. Finally, retention of the straight runway avoidance response was tested. Histological verification revealed a group with consistent parietal damage but also a subgroup with relatively small lesions to dorsal or lateral hippocampus in addition to parietal damage (PC + HIP). Behavioral results revealed virtually perfect maze retention for CON and PC rats. In contrast, PC + HIP rats were severely impaired in maze retention performance. Retention of the straight runway avoidance response was perfect in CON and PC rats but was impaired in PC + HIP rats. Vibrissae clipping did not affect error performance in the maze but led to a transitory increase in runtime. Overall, the results indicate that parietal lobe damage shortly after acquisition does not impair retention performance of young rats in the 14-unit T maze, unless hippocampal damage is also evident. Thus, parietal lobe dysfunction alone would not appear to be involved in the age-related retention impairment previously observed in this task. PMID- 2326339 TI - Genetically epileptic rats show a pronounced intermediate stage of sleep. AB - Rats of the genetically epileptic WAG/Rij strain show a more long-lasting intermediate stage of sleep compared to rats of the Wistar strain. Therefore the WAG/Rij strain provides a privileged model for studying this stage of sleep. On the other hand, the percentage of paradoxical sleep in WAG/Rij rats is lower than in Wistar rats, for the reason that the intermediate stage in WAG/Rij rats is less frequently followed by paradoxical sleep and more frequently by slow wave sleep and especially by arousals. It is speculated that the epileptic rats encounter a greater difficulty in entering into paradoxical sleep. PMID- 2326340 TI - Influence of cold pain in the hand on skin impedance, heart rate and skin temperature. AB - Twenty-one healthy volunteers took part in the study, the aim of which was to determine the influence of acute pain on skin impedance, skin temperature and heart rate. Acute pain was induced by cold exposure. Skin impedance, heart rate and facial skin temperature were recorded before, during and after the painful stimulation. The skin impedance increased during the stimulation by 24%, heart rate by 6% and skin temperature by 6%. The results show that changes in skin impedance as a result of acute pain can easily be recorded and could be a useful tool in monitoring acute pain. The technique is better than monitoring heart rate or skin temperature. PMID- 2326342 TI - Long-term habituation to a danger stimulus in the crab Chasmagnathus granulatus. AB - A shadow moving overhead acts as a danger stimulus and elicits an escape response in the crab Chasmagnathus granulatus, that habituates after 15 stimulus presentations at 3-min intervals. Here, the habituation was induced by 3 diverse shadow stimuli and the habituated response persisted after 24 hr in every case. This long-lasting effect failed to appear if the testing stimulus did not keep the same spatial specificity as that of the training one. A partial stimulus generalization was detected, when training and testing stimuli differed in size. The adaptive value of a high danger stimulus specificity in long-term habituation is discussed. Extinction of the long-term habituated response failed to occur although crabs were exposed to the context in the absence of danger stimulation. PMID- 2326341 TI - Adrenalectomy-induced memory deficits: role of plasma glucose levels. AB - Circulating glucose levels regulate memory storage under several conditions. This study examined the contribution of blood glucose levels to the transient memory impairment seen in adrenalectomized rats. Inhibitory (passive) avoidance retention performance, blood glucose levels, and glycemic responses to footshock were tested 1, 2, and 8 days after adrenalectomy. Adrenalectomized animals demonstrated a transient inhibitory avoidance deficit 1 and 2 days after surgery which recovered by 8 days. The adrenalectomy-induced memory deficit was accompanied by decreased resting blood glucose levels. In animals tested 2 days after adrenalectomy, this decrease in baseline blood glucose levels was exacerbated by further reductions, rather than the normal increases, in circulating glucose levels after training. The magnitude of blood glucose increases after glucose injection was decreased in adrenalectomized animals tested 2 days after surgery. Posttraining glucose injections restored the retention performance of animals trained 2 days after adrenalectomy to that of sham-operated animals. These findings suggest that abnormalities in blood glucose regulation may contribute, in part, to the transient memory impairment seen after adrenalectomy. Additionally, the results further implicate blood glucose in the regulation of CNS information processing systems. PMID- 2326343 TI - Effects of dorsal and medial cortex lesions on reversals in turtles. AB - Two experiments were performed to investigate the effect of cortical lesions on the acquisition and reversal of simultaneous discriminations in turtles. The first experiment examined the effect of cortical lesions on the acquisition and reversal of a spatial discrimination. The results of the first experiment revealed that lesions of the dorsal cortex produced a deficit in spatial learning. The results of the first experiment also revealed that when damage to the dorsal cortex was accompanied by substantial damage to the medial cortex, no deficit was manifest. The second experiment examined the effects of cortical lesions on the acquisition and reversal of a brightness discrimination. The results of the second experiment revealed that damage to neither the dorsal cortex nor the medial cortex produced a deficit. It was suggested that brightness is not represented in the thalamofugal visual pathway but is instead represented in the tectofugal visual pathway in reptiles. It was also suggested that the medial cortex, which is the evolutionary precursor to the mammalian hippocampal formation, functions differently from the mammalian hippocampus. PMID- 2326344 TI - Histamine in brain may have no role for histaminergic control of food-related drinking in the rat. AB - Adult male Sprague-Dawley rats surgically fitted with a cannula positioned in the third cerebral ventricle were tested for drinking after exogenous histamine or after eating with or without antagonism of H1 and/or H2 receptors for histamine using intracerebroventricular (ICV) dexbrompheniramine (DXB; 12.5-50 micrograms) or cimetidine (C; 25-100 micrograms). Histamine (0.06-16 micrograms) given ICV failed to elicit drinking. For rats drinking in response to subcutaneous (SC) histamine, ICV DXB alone did not affect drinking, whereas ICV DXB plus C, and ICV C given alone inhibited drinking. Such inhibition appeared to be relatively selective for drinking elicited by SC histamine, because ICV 50 micrograms DXB plus 100 micrograms C abolished drinking elicited by SC histamine, but failed to inhibit drinking after 12-hr water deprivation. When rats ate and drank after food deprivation, ICV DXB alone and ICV DXB plus C did not significantly inhibit food-related water intake. The inhibition of food-related drinking by ICV 100 micrograms C given alone was accompanied by inhibition of eating. In summary, histamine had unimpressive dipsogenic effects when given ICV, ICV DXB and C inhibited drinking elicited by SC histamine, but ICV DXB and C failed to inhibit food-related drinking in a manner parallel to the selective effects of intraperitoneal injection of these drugs on drinking elicited by eating. This suggests that it is histamine and histamine receptors in the periphery rather than in brain that have the predominant role for a histaminergic mechanism for drinking elicited by eating in the rat, but our findings do not rule out a role(s) for histamine in brain in the control of ingestive behavior. PMID- 2326345 TI - Hyperphagia in rats produced by a mixture of fat and sugar. AB - The hyperphagic and weight-promoting effects of feeding rats a sugar-fat mixture were compared to those of presenting only one of the two nutrients. Experimental groups were fed sugar (sucrose), fat (corn oil), or a sugar-fat mixture as an option to chow; options were in the form of water solutions or emulsions. The control group was fed only chow. The sugar-fat group displayed a robust hyperphagia (greater than 36%), relative to the control group; the hyperphagic response was greater than that observed in the fat group but not in the sugar group. The sugar-fat group selected more calories from the option than the other two experimental groups. Body weight gains were also greater in the sugar-fat group than in the fat and sugar groups. Addition of saccharin to the fat emulsion increased fat and total intakes to levels close to those of the sugar-fat mixture. In a second experiment, the relative palatability of the plain and sweet fat emulsions was assessed with two-bottle preference tests. The sugar-fat mixture was preferred to the saccharin-fat mixture, which in turn was preferred to the plain-fat emulsion. These results suggest that the sweetness of the sugar fat mixture contributed to the pronounced hyperphagia and obesity obtained with this diet option. PMID- 2326346 TI - Restricted daily exposure to environmental enrichment increases the diversity of exploration. AB - The temporal parameters of environmental enrichment have been examined in two ways. The first is by limiting the total duration of environmental exposure. The effects of this procedure are well documented for both physiology and behavior. The second method is by restricting the daily exposure to environmental enrichment while keeping the days of exposure constant. The physiological effects of this procedure have been documented, but the behavioral effects which have been observed are equivocal. The purpose of the present study was to address this issue. Male rats were individually housed at 44 days of age. They were then randomly assigned to either an enriched environment or an impoverished environment. The enriched animals (EC) were exposed to the enriched environment for 2 hours daily for 30 days while the impoverished animals (IC) were handled daily but not exposed to the enriched environment. Animals were then tested on an object exploration test. The results indicate that 2 hours of daily environmental exposure is sufficient to produce object exploration effects similar to those produced by 24 hours of daily environmental exposure. PMID- 2326347 TI - The induction by testosterone of aromatase activity in the preoptic area and activation of copulatory behavior. AB - A series of 4 experiments was designed to study the relationships between the activity of the aromatase (AA) in the preoptic area (POA) and the activation by testosterone (T) of copulatory behavior in gonadectomized male and female Japanese quail. The induction of AA by T in the POA is dose- and time-dependent. Levels of AA seen in sexually mature males are restored in castrated birds by a treatment with 20 to 40 mm silastic T capsules which produce physiological levels of steroid in the plasma. The minimal dose of T (10 mm implant) which reliably restores copulatory behavior approximately doubles the AA in the POA. The induction of AA is significantly larger in males than in females. A significant increase in AA is observed within 16 hours after the start of the treatment with T and the induction is maximal after 48 hours. Activation of copulatory behavior follows a similar time course but occurs with a delay of 24-48 hours. These results thus suggest that, in male quail, the activity of the aromatase in the POA is a limiting factor in the activation of copulatory behavior. This idea is confirmed by direct experimentation using an aromatase inhibitor, androstatrienedione (ATD). If T-treated birds receive at the same time silastic implants filled with ATD, the activation of behavior is suppressed for at least one week. This behavioral inhibition is, as expected, accompanied and very probably caused by the inhibition of the aromatase activity in the preoptic area and anterior hypothalamus. No increase of enzyme activity over the level seen in castrates was actually detected during the first 8 days of exposure to T. A moderate increase in AA was seen on day 16 and is probably responsible for the behavioral activation which was observed at the end of the experiment. PMID- 2326348 TI - Short photoperiods affect male hamster sociosexual behaviors in the presence and absence of testosterone. AB - Male hamsters were exposed to long (LD 14:10) or short (LD 8:16) photoperiods (LP; SP) to evaluate the effects of these environmental conditions on sociosexual behaviors. In Experiment 1, gonadally intact males in SP exhibited deficits in sexual behavior, reflected both in performance as well as initiation measures. Some aspects of the males' chemoinvestigation of females or their odors were also significantly different between LP and SP hamsters. In Experiment 2, castration resulted in the development of copulatory impairments, but they occurred more rapidly among males in SP conditions. Subsequent testosterone (T) replacement restored mounts, intromissions and ejaculations on tests given 2 and 4 weeks after T, but this happened more quickly in the LP group. SP males were still slower than LP males to initiate mounts and intromissions on their second test. These influences of photoperiod are discussed in the context of steroid independent and steroid-dependent effects on behavior and the role of impaired processing of chemosensory information is evaluated. PMID- 2326349 TI - Clinical and ultrastructural studies of Romberg's hemifacial atrophy. AB - Romberg's disease is an uncommon and poorly understood condition manifested by progressive hemifacial atrophy of skin, soft tissue, and bone. In order to better define the natural history and anatomic variation of this disorder, we evaluated 41 patients by history, physical examination, and facial radiographs. Light microscopic studies were performed on tissue from 19 patients, and ultrastructural analysis was performed on specimens from 6 patients. The average age at inception of the disease was 8.8 years. Atrophy, within one or more trigeminal nerve dermatomes, progressed at a variable rate (mean period of active tissue dissolution = 8.9 +/- 6 years). In 26 patients with skeletal involvement, the mean age of onset was 5.4 years, versus 15.4 years for 15 patients without skeletal involvement, a statistically significant difference (p less than 0.01). However, there was no correlation between the severity of soft-tissue deformity and the age of onset. Electron microscopy demonstrated lymphocytic infiltrates in neurovascular bundles and abnormalities of vascular endothelium and basement membranes. We hypothesize that the pathogenesis of Romberg's disease involves chronic cell-mediated vascular injury and incomplete endothelial regeneration along branches of the trigeminal nerve (lymphocytic neurovasculitis). PMID- 2326350 TI - The operative treatment of isolated craniofacial dysostosis (plagiocephaly): a comparison of the unilateral and bilateral techniques. AB - Both the safety and efficacy of the treatment of isolated craniofacial dysostosis (plagiocephaly) in infancy have been demonstrated. Opinions remain divided, however, as to the optimal type of procedure to be undertaken. In an attempt to answer this question, we have retrospectively evaluated a study population of 48 children operated on in infancy by either a unilateral or bilateral approach. Results of treatment at a minimal follow-up of 3 years were assessed based on preoperative and postoperative photographs and direct patient examination. Based on this retrospective comparison of the unilateral and bilateral approaches to the treatment of isolated craniofacial dysostosis, we conclude that (1) either approach as specifically outlined will give excellent results in the majority of patients, (2) there is no statistically significant difference in the results obtained by using either procedure, (3) in the majority of instances, less than ideal correction was manifested by contour irregularities evident in the temporal and/or lateral forehead region, and strict attention should be given to these areas in an attempt to further improve results, and (4) in those cases where significant protrusion is observed on the "normal side," a bilateral approach is preferable. PMID- 2326351 TI - Levator veli palatini muscle and eustachian tube function. AB - Thirty previously unoperated patients with submucous cleft palate, occult submucous cleft palate, and unilateral congenital paralysis of the levator veli palatini muscle were examined. All patients were subjected to a comprehensive otoscopic, endoscopic, audiologic, and tympanometric evaluation. A correlation was made between levator veli palatini muscle anomalies, eustachian tube orifice anomalies, and middle ear ventilation and disorders. Normal middle ear ventilation was found in 23 patients. Negative middle ear pressure that consequently normalized following treatment of coexisting sinusitis was found in 3 patients. Only in 4 patients was chronic middle ear disease found. In one of them, middle ear effusion disappeared following successful treatment of sinusitis. Our conclusion is that the levator veli palatini muscle has no significant function in the opening mechanism of the eustachian tube and must be considered as a velopharyngeal valve muscle only. PMID- 2326352 TI - The relationship of retrobulbar hematomas to vision in cynomolgus monkeys. AB - An experimental model has been developed to measure the effect of retrobulbar hematomas on functional vision in cynomolgus monkeys. In this model, functional vision was quantitated using flashed evoked visual potentials in five monkeys following creation of retrobulbar hematomas. In one monkey used as a control, functional vision remained impaired for 180 minutes following induction of retinal ischemia by increased intraorbital pressure. In two monkeys in which increased intraorbital pressure was relieved by anterior chamber paracentesis following 15 minutes of retinal ischemia, flashed evoked visual potential promptly returned to baseline level. In two additional monkeys in which increased intraorbital pressure was relieved following 30 minutes of retinal ischemia, flashed evoked visual potentials improved but never returned to baseline levels. This study demonstrates the usefulness of flashed evoked visual potentials in measuring functional vision in cynomolgus monkeys. This experimental model should prove useful in evaluating the effects of increased intraorbital pressure on functional vision and the effect of intervention on impaired vision due to retrobulbar hematomas. Further studies with larger numbers of animals are needed to clarify these preliminary studies and document longer-term effects of retinal ischemia secondary to retrobulbar hematomas. PMID- 2326353 TI - Skeletal stability after Le Fort I maxillary advancement in patients with unilateral cleft lip and palate. AB - Outcomes in 30 adults and adolescents judged skeletally mature who had unilateral cleft lip and palate and underwent Le Fort I advancement were investigated to determine amount and timing of relapse, correlation between advancement and relapse, effect of performing multiple jaw procedures, effect of different types of bone grafts, effect of pharyngoplasty in place at the time of osteotomy, and effectiveness of various methods of internal fixation. Tracings of preoperative and serial postoperative lateral cephalograms were digitized to calculate horizontal and vertical maxillary changes. No significant differences in outcome was seen between patients who had maxillary surgery alone and those who had operations on both jaws, nor did the outcome vary significantly with the type of autogenous bone graft used or the segmentalization of the Le Fort osteotomy. Mean "effective" advancement was greater immediately and 2 years after surgery in those patients who did not have a pharyngoplasty in place before the operation. Advancement also was greater immediately and after 2 years in the miniplate fixation group than in patients with direct-wire fixation. Mean downward (vertical) displacement was 2.6 mm with a relapse of 1.4 mm after 2 years. Amounts of relapse and of advancement or displacement did not correlate significantly. PMID- 2326354 TI - Rigid stabilization of sagittal fractures of the maxilla and palate. AB - Rigid stabilization of sagittal fractures of the palate is described that utilizes plate and screw fixation in the palatal vault. Accurate reduction of facial width is obtained, and stability is significantly enhanced. An existing laceration or a longitudinal incision in the palatal mucoperiosteum provides exposure for maxillary adaption plate application. The transpalatal reduction should be supplemented by fixation at the piriform aperture, the zygomaticomaxillary and nasomaxillary buttresses, and by the use of an arch bar. Since slower bone healing may be observed following palatoalveolar fractures, the occlusion must be observed for deviation throughout a full 16-week period even though early motion and soft diet are permitted. Removal of the plate and screws in the roof of the mouth is sometimes required and utilizes local anesthesia. PMID- 2326355 TI - Resection of obstructing inferior turbinates following rhinoplasty. AB - Total inferior turbinectomy was carried out in 38 patients who complained of nasal obstruction following rhinoplasty or rhinoseptoplasty and in whom hypertrophied inferior turbinates were found to be the cause of obstruction. Postoperatively, relief of nasal obstruction was reported by 84 percent of patients, while rhinoscopy showed wide, clean nasal airways in 92 percent. Nasal airflow measurements in 32 tested patients showed increased patency in all of them, including 3 who still complained of nasal obstruction postoperatively. The follow-up period ranged from 1 to 7 years (mean 2.8 years). Atrophic changes of the nasal mucosa or chronic purulent infection was not observed in any of the patients. Because the results of partial procedures on the inferior turbinates are often unsatisfactory, I suggest performing total inferior turbinectomy in patients with obstructing inferior turbinates following rhinoplasty. PMID- 2326356 TI - Aesthetic results following partial mastectomy and radiation therapy. AB - This study was undertaken to determine the aesthetic changes inherent in partial mastectomy followed by radiation therapy in the treatment of stage I and stage II breast cancer. A retrospective analysis of breast cancer patients treated according to the National Surgical Adjuvant Breast Project Protocol B-06 was undertaken in 57 patients from 1984 to the present. The size of mastectomy varied between 2 x 1 cm and 15 x 8 cm. Objective aesthetic outcome, as determined by physical and photographic examination, was influenced primarily by surgical technique as opposed to the effects of radiation. These technical factors included orientation of resections, breast size relative to size of resection, location of tumor, and extent and orientation of axillary dissection. Regarding cosmesis, 80 percent of patients treated in this study judged their result to be excellent or good, in comparison to 50 percent excellent or good as judged by the plastic surgeon. Only 10 percent would consider mastectomy with reconstruction for contralateral disease. Asymmetry and contour abnormalities are far more common than noted in the radiation therapy literature. Patients satisfaction with lumpectomy and radiation, however, is very high. This satisfaction is not necessarily based on objective criteria defining aesthetic parameters, but is strongly influenced by retainment of the breast as an original body part. PMID- 2326357 TI - Extensive wounds of the spine: a comprehensive approach to debridement and reconstruction. AB - Extensive wounds involving the spine (greater than three vertebral segments exposed) may threaten its indispensable roles of biomechanical support and vital neurologic function. Although there have been select reports of specific flap applications in this body region in the reconstructive surgical literature, there has been a paucity of comprehensive descriptions of pertinent anatomy, pathophysiology, and the perioperative care of such patients--including the degree to which the spine is suited to aggressive debridement. Four patients with complex spine wounds involving greater than three vertebral segments were treated by the authors from 1986 through 1988. These patients ranged from 28 to 80 years of age. They were all found to have multiple risk factors, including neoplasm (4), severe nutritional depletion (3), advanced age (2), wound sepsis (2), and multiple other general medical problems (4). All patients underwent wide bony and soft-tissue debridement. A new clinically essential four-pillar concept of spinal support predicted spinal instability in two of the four patients. These patients could thus be protected from neurologic compromise with internal stabilization (1) or external orthotic support (1). Wound closure was achieved with skin graft (1) or traditional or extended musculocutaneous flap coverage (3). With 7 to 20 months of follow-up, wound healing has been complete in all patients despite a 100 percent complication rate and one late postoperative death. Multisegment spine wounds tend to arise in the setting of multiple medical problems or risk factors. Despite these risk factors and a high postoperative complication rate, gratifying results may be achieved in these patients with a comprehensive understanding of regional surgical anatomy and a multidisciplinary approach to their care. PMID- 2326358 TI - The treatment of burn scar hypopigmentation and surface irregularity by dermabrasion and thin skin grafting. AB - Scar tissue and leukoderma-type discoloration of the skin due to deep burns are treated by dermabrasion and thin split-thickness skin-graft application. This method was applied to 18 patients on whom the treated lesion sites were located as follows: 8 in the facial area, 9 on the extremities, and 1 on the neck. Adequate repigmentation and flat surfaces were obtained in all patients at the end of 6 months, and results persist at the end of a considerable follow-up period (1 to 4 years). The technique, advantages, disadvantages, and results are discussed. PMID- 2326359 TI - The medialis pedis flap: a new fasciocutaneous flap. AB - An anatomic study (30 fresh specimens dissected) and clinical experience (5 patients) have shown the reliability of a fasciocutaneous flap raised from the medial side of the foot. The artery that supplies the flap is issued from the medial plantar artery. The arch of rotation allows one to cover some specific areas, such as the medial malleolus, posterior aspect of the heel, and distal insertion of Achilles tendon. PMID- 2326360 TI - Rat ear reattachment as an animal model. AB - The external ear of the rat is an excellent model for practicing microsurgical dissection and for the refinement of microvascular anastomoses, techniques that are crucial for microvascular en bloc tissue transfer and replantation. Preparation of the rat ear for replantation requires familiarity with the vascular anatomy and gentle tissue handling with atraumatic dissection of arterial and venous pedicles, steps similarly crucial in raising free flaps for microvascular transfer. The strategy of performing accurate reduction and stabilization of the tubal cartilage prior to vessel repairs, anastomosing the more deeply seated external carotid artery prior to the more superficial posterior facial vein, is as critical to rat ear replantation as for digital reattachment. In addition, the rat ear as compared to other animal models such as the rabbit ear or canine hindlimbs is much less expensive. Compared to the rat hindlimb model, rat ears are much easier to observe, which is a distinct advantage when used as a model for long-term study of replantation, revascularization, or transplantation. PMID- 2326361 TI - Secondary ischemia time in rodents: contrasting complete pedicle interruption with venous obstruction. AB - The current study investigated the effect of secondary ischemic insults on ultimate flap survival. Rodent skin flaps subjected to 8 hours of secondary ischemia with total pedicle obstruction had 56 percent survival (7 of 12) compared with primary ischemic flaps of the same time, which all survived. At 10 hours of ischemia, only 42 percent of secondary ischemic flaps survived compared with 67 percent (8 of 12) of primary ischemic flaps. When the secondary ischemia was caused by venous obstruction, the results were even more striking. Ninety-two percent (11 of 12) of primary venous obstruction flaps survived 3 hours of ischemia and 75 percent (9 of 12) survived 5 hours of ischemia, while only 56 percent (7 of 12) and 8 percent (1 of 12) of flaps subjected to secondary venous obstruction survived at the same times, respectively. The explanation of these observations on the basis of tissue pathophysiologic changes will require further study. The results support the need for close monitoring of clinical flaps to ensure optimal survival. PMID- 2326362 TI - Stealing patients. PMID- 2326363 TI - Congenital skin fossae about the shoulder. AB - Congenital fossae, skin pits, or dimples can form about the shoulder. Little has been written about congenital supraspinous fossae or dimples. They are thought to result from the catching of tissues between a sharp bony post and the uterine wall. The skin and structures become compressed and adherent, and when the pressure is released, the surrounding parts remain tied down, forming small pits or dimples. I report on a congenital fossa in the scapular region of an infant who cried each time the arm was abducted. This congenital fossa did communicate with and adhered to the scapula. Excision of the fossa with its surrounding scar tissue about the scapula plus gentle manipulation gave free motion to the shoulder. PMID- 2326364 TI - The coracobrachialis muscle flap for coverage of exposed axillary vessels: a salvage procedure. AB - The coracobrachialis muscle has been suggested for possible use in coverage in infraclavicular defects, specifically in postmastectomy reconstructive patients. This case report demonstrates the successful clinical use of this flap for coverage of exposed axillary vessels in the infraclavicular area. Anatomy and techniques of dissection are reviewed as well as potential disadvantages. PMID- 2326365 TI - Total reconstruction of a two-compartment scrotum by tissue expansion. AB - A case report is presented showing the reconstruction of a two-compartment scrotum out of hair-bearing perineal skin following a severe degloving injury of the scrotum and testicles. We feel that this is an appropriate procedure to be used in patients who have lost the testicles and scrotum traumatically, either one or both testicles, or in the situation where both testicles have been spared. Aesthetically, the result in this patient is superior to skin grafting and should be readily reproducible. PMID- 2326366 TI - Breast capsulopexy for capsular ptosis after augmentation mammaplasty. AB - A simple and reliable technique of capsulopexy is presented. A total of six inferiorly displaced inframammary folds were thus corrected during the past 8 years with good results and with an average of 3.2 years of follow-up. It is felt that this method is simple, reliable, and easier than other techniques previously reported in the literature. PMID- 2326367 TI - Seroma after latissimus dorsi myocutaneous flap for breast reconstruction. PMID- 2326368 TI - Measuring the volume of defects of the head and face. PMID- 2326369 TI - Tissue expansion in conjunction with rhytidectomy. PMID- 2326370 TI - Autologous blood transfusion in plastic surgery. PMID- 2326371 TI - Simplified gracilis harvesting. PMID- 2326372 TI - Transconjunctival blepharoplasty. PMID- 2326373 TI - Calf implants. PMID- 2326374 TI - A plea for "experimental surgery" supplement. PMID- 2326375 TI - [Acoustically evoked brain stem potentials in acute alcoholic intoxication]. AB - Under the acute influence of alcohol with blood alcohol concentrations (BAK) ranging between 0.62 to 2.04%, the IPL prolongations of our subjects were within standard deviations compared with normal data. Depending on the BAK, these minor IPL alterations hint at a special vulnerability in the pontomesodiencephal area. The increase in BAK significantly correlates with the reduction of body temperature. The BAEP proves to be suitable for defining undear states of coma different origin. PMID- 2326376 TI - [Symptoms of dementia misdiagnosed as psychosocial development disorder in congenital aqueduct stenosis]. AB - The paper describes a case in which symptoms of dementia basing on a chronic psycho-organic syndrome together with congenital aqueduct stenosis were for years erroneously regarded as indicating psychosocial maldevelopment. Emphasis is laid on the need to consider the possibility of a process of dementia, even if maldevelopment of the personality only displays mild neurological symptoms. PMID- 2326377 TI - [10 years' comparison of inpatient treated affective diseases]. AB - A comparison was carried out between 237 hospitalised patients with emotional disorders during the years 1972-1975, and 316 patients between 1982 and 1985. The number of admissions as a percentage of all psychiatric admissions rose from 18.21% to 26.49%. There was a significant rise in the number of readmissions, notably from the third admission upwards, but a considerable reduction in the length of stay in hospital. During the period the number of admissions to general hospitals within the catchment area was reduced by about one half, with the result that there was no appreciable overall increase in the number of admissions for in-patient treatment of emotional disorders in the ten-year period. PMID- 2326378 TI - [The effect of autogenic training on cortisol and leukocytes]. PMID- 2326379 TI - [Traditional treatment procedures in neurologic-psychiatric diseases in Ethiopia]. AB - This is a report, based on a one year's stay at the hospital of the Gondar College of Medical Sciences (PDR Ethiopia), on the usage of traditional therapeutic practices as described by patients of the neurologic-psychiatric department in their histories. More frequently than others, psychotic patients, patients suffering from headache, and patients complaining of fits had used traditional treatments before seeking medical help. PMID- 2326380 TI - The profile of a major affective disorder offender. AB - The authors review the studies on the relationship between crime and mental disorder conducted in various settings and point out that the incidence of major mental illnesses in general and of major affective disorders in particular, among the criminal population is relatively small. They present the profile of a major affective disorder offender presenting at a forensic psychiatric department of a university-based psychiatric hospital in a major Canadian city. This profile is based on the demographic, psychiatric, psychological and legal data on a sample of 46 consecutive patients with a diagnosis of major affective disorder. Even though the majority of these offenders are charged with relatively minor crimes and property offenses, they are often referred by the courts for in-patient assessment as many show active symptoms at the time of initial appearance in court. The ways the criminal justice system deals with these offenders are discussed. The benefits and limitations of describing a profile of any group of offenders are also considered. PMID- 2326381 TI - Alcohol withdrawal concealing symptoms of subdural hematoma--a caveat. AB - Symptoms of significant medical illnesses, in this case subdural hematoma, is easily overlooked in midst of alcohol withdrawal. Unusual symptoms must be regarded with caution. PMID- 2326382 TI - Holocaust survivors: a clinical perspective. AB - At the end of World War II there was a conspicuous absence of response by the psychiatric profession to the challenge of rehabilitating the survivor and virtually no reference to the psychiatric consequences or treatment approaches in major psychiatric textbooks. Despite a growing literature, attention was not re focussed on the Holocaust survivor until the advent of the DSM III with PTSD as a defined diagnostic category. In my nearly twenty years of psychiatric practice, there has been a steady stream of Holocaust survivors and their children presenting with various problems. In the last decade a number of "child survivors" (those under age 16 at the conclusion of the war) have also presented with first breakdowns, depressive or otherwise, and always with strong links to the Holocaust experience. PMID- 2326383 TI - Associated diagnoses (comorbidity) in patients with borderline personality disorder. AB - The authors administered the Diagnostic Interview Schedule to 21 patients with borderline personality disorder. The patients met criteria for various other DSM III diagnoses, meeting exclusion criteria in some cases, and not in other cases. Frequency distribution of each diagnosis and the diagnoses of each individual patient, are presented. Affective disorder was the most common diagnosis (85%). Of these, 62% had primary major depression, and 23% had secondary depression. Other diagnoses include bipolar disorder, dysthymia, panic, agoraphobia, alcohol and Drug abuse, somatization disorder, and many others. The authors conclude that while borderline disorder may be a sub-affective disorder, a specific diagnostic profile for this disorder that accounts for the presence of other Axis I and Axis II syndromes has yet to be delineated. PMID- 2326384 TI - Resolving the conflict of training and therapy in psychiatry. AB - This paper poses the question of whether psychiatric patients are disadvantaged by their exposure to psychiatric residents. The advantages and disadvantages of short residency rotations both for patient treatment and resident education are examined. Recommendations are suggested for alternative models of supervision which may reduce the negative effects of short-term rotations on therapeutic outcome and result in improved educational opportunities for psychiatric residents, especially in the area of chronic care. PMID- 2326385 TI - A prospective study of psychosocial aspects of gastric stapling surgery. AB - Sixteen patients who underwent gastric stapling procedure for morbid obesity were assessed pre- and post-operatively on several psychosocial dimensions using a number of self-report questionnaires including the Eating Disorders Inventory, Locus of Control, and Millon's Clinical Multi-Axial Inventory. Subjects' responses to questions regarding their socialization, lifestyle and sexual relations were also compared for the two periods. The mean interval between surgery and completion of follow-up questionnaires was 13.6 months. Eighty-one percent of the patients showed an improvement in their psychosocial profile as measured by the MCMI. Although some residual difficulties were reported, generally patients were pleased with their physical appearance and experienced an improvement in current relationships and sexual functioning. Overall, the results indicate a favorable psychosocial outcome following gastric stapling surgery. PMID- 2326386 TI - Referral barriers--near failure to thrive of a group. AB - This paper describes the purpose, goals and painful beginnings of a free group service to chronic, low functioning, psychiatric outpatients in a hospital system. The 'Thursday Group' was first made available in 1985 for patients who are depressed, psychotic or otherwise severely emotionally disturbed. It has few restrictive criteria, yet it nearly 'failed to thrive' and almost perished due to lack of referrals. This paper focuses on some possible reasons for the referral barriers. They include the degree of visibility of the therapist in the system, habit and the status of group treatment in the minds of staff, the dynamics of these patients and patient-staff relationships, the staff's own dynamic and their position within the system, and finally the understanding of the limits and capacities of a group. The therapeutic value of the group and its more hopeful current place in the system is described. PMID- 2326387 TI - Simultaneous Folie a Deux and Capgras syndrome. AB - A young male presented both Capgras syndrome and Folie a Deux. Both of his parents shared the same delusions with the patient. A dynamic explanation is provided for the simultaneous occurrence of both syndromes. The case report and the management of this patient may be of interest to clinicians. PMID- 2326388 TI - An unusual case of Capgras syndrome: the psychiatric ward as a stage. AB - A 31-year-old male psychiatric patient presented with an unusual multifaceted delusion of misidentification including Capgras syndrome, in which people in the immediate environment, the other patients and hospital staff, were seen as hired actors in a stage production. The genesis and reinforcement of his delusional thinking appears to be the results of psychological, organic, and ecological factors. PMID- 2326389 TI - [A hysterical symptom of astasia-abasia in a young male]. PMID- 2326390 TI - A patient with panic disorder eventuating in psychosis: nosology implications, Vol. 14, No. 3, September, 1989. PMID- 2326391 TI - Seizure in gradual clonazepam withdrawal, Vol. 14, No. 3, September, 1989, p. 484. PMID- 2326392 TI - Reduced haloperidol/haloperidol ratios in plasma: polymorphism in Japanese psychiatric patients. AB - We measured plasma concentrations of haloperidol (HAL) and its metabolite, reduced haloperidol (RHAL), by high performance liquid chromatography (HPLC) in 45 Japanese psychiatric patients receiving HAL. Plasma levels of HAL had a highly positive correlation with daily dose per body weight. Plasma RHAL/HAL ratios had also a dose-dependent relationship, but their distribution was nonnormal and a bimodal pattern with an antimode at 0.7 was apparent by probit analysis. There were 8 subjects (18%) with high RHAL/HAL ratios (mean = 1.26, SD = 0.41) and 37 subjects (82%) with low RHAL/HAL ratios (mean = 0.42, SD = 0.13). RHAL/HAL ratios showed little intraindividual variability (+/- 10.6%), while interindividual variability was large. This may suggest that pharmacogenetic factors are involved in the metabolism of HAL and RHAL. PMID- 2326393 TI - Prevalence of seasonal affective disorder at four latitudes. AB - The Seasonal Pattern Assessment Questionnaire (SPAQ) was mailed to a sample population balanced for sex and randomly selected from local telephone directories in four areas: Nashua, NH, New York, NY, Montgomery County, MD, and Sarasota, FL. On the basis of responses to this questionnaire, prevalence rates of winter seasonal affective disorder (winter SAD), summer seasonal affective disorder (summer SAD), and subsyndromal winter SAD were estimated for the four areas. Rates of winter SAD and subsyndromal SAD were found to be significantly higher at the more northern latitudes, while no correlation was found between latitude and summer SAD. The positive correlation between latitude and prevalence of winter SAD applied predominantly to the age groups over 35. PMID- 2326394 TI - Sources of discrepancy in the comparison of a lay-administered diagnostic instrument with clinical diagnosis. AB - This article presents a comparison of the diagnostic results from a lay administered diagnostic interview for depression with a clinical diagnosis in a community sample. The purpose of the comparison is to assess reasons for the discrepancies between the two diagnostic approaches. The majority of the discrepancies result from inconsistent episode reports at the two interviews. We propose a number of possible explanations for the inconsistencies. An empirical analysis that identifies predictors of consistent vs. inconsistent reports supports a strong influence for respondent recall error. We discuss the implications of our analysis for previous comparisons of lay-administered and clinical diagnostic instruments. PMID- 2326395 TI - Impaired effortful cognition in depression. AB - Depressed patients have been reported to have deficits in "effortful," but not effortless, cognitive functions compared to healthy volunteers. To test the hypothesis that the effortful cognitive deficits in major depression are not simply a function of psychiatric illness or hospitalization, we administered both effort-demanding and effortless cognitive tasks to 17 inpatients with major affective disorder and 17 hospitalized psychiatric controls. The depressed patients performed significantly more poorly than the controls on the effort demanding task. The groups did not differ on the effortless task. These findings suggest that depressed patients are impaired in performing effort-demanding cognitive tasks compared to nondepressed psychiatric patients. PMID- 2326396 TI - Information processing deficits of schizophrenic children with formal thought disorder. AB - The relations among formal thought disorder, the partial report span of apprehension task, the distractibility factor on the Wechsler Intelligence Scale for Children-Revised (WISC-R), and IQ scores were examined in 31 schizophrenic children, aged 7.4 to 12.5 years. The partial report span of apprehension scores of the schizophrenic children correlated significantly with their illogical thinking scores. Their scores on loose associations were significantly associated with the WISC-R distractibility factor score. The attention/information processing deficits that might underlie the clinical manifestations of illogical thinking and loose associations in childhood onset schizophrenia are discussed. PMID- 2326397 TI - Psychological test characteristics of depressed and panic patients. AB - This study compared the psychological test performance of patients with major depression (MD) (n = 23), patients with panic disorder (PD) (n = 20), and normal subjects (n = 24). Results indicated that scores of normal subjects were significantly less pathological than those of both patient groups on almost all psychological test scales, but that the test performance of the two patient groups did not differ. The only difference between the two patient groups was on the level of self-reported and observer-rated depression. Both patient groups exhibited significant personality pathology, and the rate of personality disorders diagnosed by the Millon Clinical Multiaxial Inventory (MCMI) (base rate greater than 84) was 73% for PD patients and 86% for MD patients. The problems of assessing personality during episodes of MD and PD and the possible overdiagnosis of personality disorders by the MCMI are discussed. PMID- 2326398 TI - Effect of amitriptyline on endocrine responses to intravenous L-tryptophan. AB - The endocrine responses to the 5-hydroxytryptamine (5HT) precursor, L-tryptophan, were assessed in 10 depressed patients before and after at least 4 weeks of treatment with amitriptyline. Overall, amitriptyline did not alter either prolactin or growth hormone responses to L-tryptophan. When three subjects with severe pretreatment weight loss were excluded, however, the remaining seven patients showed a significant increase in the prolactin response to L-tryptophan, consistent with other published studies. The findings suggest that severe recent weight loss may alter the effects of tricyclic antidepressants on 5HT-mediated prolactin release. PMID- 2326399 TI - Panic disorder: a presynaptic serotonin defect? PMID- 2326400 TI - Mechanisms of anxiogenic vulnerability in panic disorder. PMID- 2326401 TI - Serum phosphate and anxiety in major depression. PMID- 2326402 TI - Selection of vigilant and avoidant coping strategies among repressors, highly anxious and truly low anxious subjects. AB - 70 female graduate students from a western university were classified as to personality type: Highly Anxious, Truly Low Anxious, and Repressing, using a combination of scores from the Taylor Manifest Anxiety Scale and the Marlowe Crowne Social Desirability Scales. Each subject's preference for monitor or blunter coping strategy was assessed via the Miller Behavioral Style Scale. Highly Anxious subjects chose significantly more monitor strategies than did Truly Low Anxious subjects or Repressors. The number of blunter strategies chosen did not differ across personality types. Chi-squared indicated that Highly Anxious subjects were more often classified as monitors than blunters whereas the proportions of monitors and blunters did not significantly differ between Truly Low Anxious subjects and Repressors. Results suggest that the repressor trait is distinct from avoidant and vigilant coping strategies. PMID- 2326403 TI - Attitudes of undergraduate college students toward AIDS. AB - This study examined attitudes about AIDS and the effects of those attitudes on the behavior of 131 undergraduate college students. Participants reported having minimal concern about contracting AIDS from their current or future sexual partners, and their rate of sexual activity had not changed from that of the previous year. Of all participants 69% reported they did not use condoms during their sexual encounters. White students were more knowledgeable about AIDS than their peers from minority groups. Although all participants were aware they could not contract the AIDS virus through common social interaction, 80% reported they would feel very anxious if a classmate who had AIDS continued to attend classes. These findings suggest that these undergraduate students underestimate their risk of HIV infection and so jeopardize their health. PMID- 2326404 TI - Capital punishment, gun control, and personal violence (suicide and homicide). PMID- 2326405 TI - Bombesin improves rats' operant responding maintained by a differential reinforcement-of-low-rates schedule of food reinforcement. AB - The present study examined rats' responding on a differential-reinforcement-of low-rates schedule of food reinforcement following intraperitoneal injections of various doses of bombesin (4, 6, 8, 16, 32 micrograms/kg). Analyses indicated that only the 6 micrograms/kg dosage improved DRL responding. The findings are consistent with prior research examining bombesin's effect on operant behavior and support the notion that bombesin induces satiety rather than malaise. PMID- 2326406 TI - Social correlates of lethal aggression. PMID- 2326407 TI - Effects of environment on psychological well-being of elderly persons. AB - This study reports an investigation of the psychological well-being of 90 elderly persons living in independent, retirement, and nursing homes. In previous studies elderly persons have not been matched on high levels of social and physical functioning across these living environments. Analyses indicated significantly that elderly persons living in their own homes or retirement homes reported greater well-being than their matched cohorts in nursing homes. PMID- 2326408 TI - Birth order and fear of success among midadolescents. AB - While among 194 high school students 79 first-borns showed less fear of negative consequences of academic success than 78 last-borns and 37 middle-borns, no differences were observed on fear of increased positive attention or of increased responsibility. PMID- 2326409 TI - Stability of the isolation/disengagement relationship across age groups. AB - Research has indicated isolated elderly persons are either engaged or voluntarily disengaged. The present assessment was whether this relationship holds across age subgroups. While the general relationship did hold true for all age groups, the 55-64 age group was less engaged than their older cohorts. The level and type of disengagement appears to be dependent upon life situations and can decrease with age. PMID- 2326410 TI - Locus of control and perceived alcohol ingestion in performance of a fine motor skill. AB - To investigate the influence of locus of control on a fine motor corrdination task where subjects had ingested or believed that they had ingested alcohol, 60 men who were enrolled in introductory psychology and scored in the upper or lower thirds of the population on Rotter's I-E Scale (30 external and 30 internal scorers) were randomly assigned to one of three treatment conditions: a control group (no alcohol expected/no alcohol received), an alcohol group (alcohol expected/alcohol received), and a placebo group (alcohol expected/no alcohol received). Pretest and posttest measures of performance on the Purdue Pegboard Test were obtained from all subjects. Subjects in the control groups were given three 6-oz. (177.4-ml) glasses of fruit punch over a 35-min. waiting period between pretest and posttest on the Purdue Pegboard. The alcohol groups drank a sufficient number of similar glasses (usually three) to produce a 0.1% measure on a breathalyzer before completing the posttest on the Purdue. Pegboard. The placebo groups were told that they were drinking an alcohol-based drink but were served three glasses of a nonalcoholic, rum-flavored fruit drink. These groups were also told that they measured 0.1% on a breathalyzer. Control groups, both internal and external scorers, showed essentially no change from pre- to posttest on the Purdue Pegboard. The alcohol groups, on the other hand, both internal and external scorers, showed a significant decrement in performance. The internal placebo group did not differ from the two control groups and showed no decrement in performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326411 TI - Cigarette-smoking reduction in university students. PMID- 2326412 TI - Differential importance of hierarchical learning, abstractness, and imagery. AB - This research examined the relative contribution of hierarchical sequencing, abstractness, and imagery to learning. In the past, hierarchical, logical sequencing was not shown to be superior to other modes of instruction, and the interaction of imagery, abstractness, and sequencing had not been examined, especially regarding the possible superiority of any of these as a contributor to learning. The data were produced by 108 high school students who studied sequences of hierarchically related information arranged in a 2 x 2 x 2 factorial design the dimensions of which varied according to the degree of imagery (high and low), abstractness (abstract and concrete), and type of sequencing (logical and scrambled). Analyses of the amount of learning under these conditions showed that hierarchical sequencing is not only relevant to learning but more related than either imagery or the abstractness of material to be learned. Additional suggestions are made regarding instruction and research especially in relation to matrix rather than hierarchial arrangements of information. PMID- 2326413 TI - Birth order and academic achievement of children in Transkei. AB - This study investigated the relationship between birth order and academic achievement of 1021 randomly chosen Standard 7 pupils in Transkei, South Africa. The subjects ranged in age from 13 to 17 yr., with a mean of 15.6 yr. Two questionnaires, one for the pupils and the other for their parents, were administered to collect information on the birth order of children. Analysis of variance indicated a significant negative relationship between birth order of children and their academic achievement. PMID- 2326414 TI - Women in the labor force and suicide. PMID- 2326415 TI - Fear of AIDS: self-reports of Australian children and adolescents. AB - Using a self-report questionnaire, we assessed fear of AIDS in Australian children and adolescents. Recently, the participants had been subjected to a community education program featuring frightening televised advertisements. A high level of fear was reported by 65.9% of the respondents. Girls reported a significantly greater mean fear than boys. Fear of AIDS was not significantly influenced by developmental factors. Given the design and measures, it was not possible to specify the origins of the fear response. PMID- 2326416 TI - If women are more often depressed, why don't more of them kill themselves? PMID- 2326417 TI - Directed attention influences the modification of startle reflex probability. AB - The present study was designed to investigate the effect of directed attention on elicitation and modification of the startle reflex. 30 adult human subjects received 90 dB(A) broadband noise startle stimuli either alone or preceded by a 60 dB(A) prepulse (either 2000-Hz tone, 1000-Hz tone, or broadband noise). Subjects were instructed to attend to one of the three prepulses during half the trials and to ignore all stimuli during the rest of the trials. The probability of responding while attending to a prepulse was significantly lower than the probability of responding while ignoring the prepulses. Responding to the prepulses was also more probable while subjects were attending to the prepulses, and these effects were more pronounced for tone than for noise prepulses. These results suggest that directed attention can influence the probability of the startle reflex without influencing startle amplitude or latency. PMID- 2326418 TI - Was gas detoxification or establishment or suicide prevention centers responsible for the decline in the British suicide rate? PMID- 2326419 TI - Effects of moderating variables on product managers' behavior. AB - This study examined the moderating effects of role autonomy, need for affiliation, and tolerance of ambiguity on the relationships between role pressures of conflict and ambiguity and personal outcomes of job satisfaction, job-related tension, and perceived performance. Data from 166 product managers indicate that role autonomy and need for affiliation do have moderating effects unlike tolerance of ambiguity. Managerial implications are discussed. PMID- 2326420 TI - Psychotherapists' religious beliefs and their perception of the psychotherapy process. AB - In a comparison of religious and nonreligious psychotherapists' perceptions of a portion of a psychotherapeutic session no significant differences were found on the Vanderbilt Psychotherapy Process Scale for four groups of therapists designated according to their scores on three religious questionnaires. While the results suggest attitudes toward religion are not reflected in therapists' practice of psychotherapy, limitations of the study indicate the need for more rigorous testing of this possibility. PMID- 2326421 TI - Revised Beck Depression Inventory scores of inner-city adolescents: pre- and postpartum. AB - The revised Beck Depression Inventory was administered to 109 (69.0%) black, 33 (20.9%) Hispanic, and 16 (10.1%) white adolescents who were attending prenatal and postpartum clinics offered by two inner-city hospitals at 28 wk. of pregnancy, 5 wk. postpartum, and 6 mo. postpartum. The mean Beck scores significantly decreased between 28 wk. of pregnancy and 5 wk. postpartum but did not change between 5 wk. and 6 mo. postpartum. The levels of depression were comparable to those previously reported for nonpregnant adolescent females. Using a Beck cut-off score greater than 20 as indicative of depression, 134 (84.8%) were never depressed; 11 (7.0%) became depressed after delivery; 8 (5.1%) ceased being depressed after delivery; and 5 (3.1%) were depressed throughout. PMID- 2326422 TI - The protestant work ethic and type A behaviour: a pilot study. AB - 40 adult subjects completed three measures of the Protestant Work Ethic and a multidimensional measure of the Type A behaviour pattern. The only consistent pattern of correlations was between the "hard-driving" subscale of the Type A measure and all three total PWE scores for Protestant Work Ethic. Results are discussed in terms of the constituent parts of both concepts. PMID- 2326423 TI - Reply to Hauck, et al. concerning nonsexual household transmission of HIV in Zaire. AB - CDC researchers mishandle statistical evidence and overstate case against casual transmission of HIV. Reassessment by Hauck, et al. is statistically inappropriate. PMID- 2326424 TI - Factor analysis of the substance abuse attitude survey with college undergraduates. AB - Few standardized instruments measure attitudes and beliefs towards substance abuse. The Substance Abuse Attitude Survey, developed for measuring drug attitudes in medical education, was administered to 598 college undergraduates, and a factor analysis was performed. Three coherent and stable factors were identified, e.g., Stereotypes and Moralism, Treatment, and Permissiveness. Internal consistency and 6-wk. test-retest measures indicated moderate to high reliability factor structure. Results are discussed in terms of sample differences between this effort and a previous validation. PMID- 2326425 TI - Race and brain weight: a note on J.P. Rushton's conclusions. AB - Rushton's (1988) reinterpretation of recent research on brain weight one-sidedly emphasizes the findings of heavier brain weight in whites than in blacks and neglects to comment on a larger difference found between men and women. Rushton explicitly used brain size as indicator of intelligence. His implicit conclusion that women are less intelligent than men is not supported by empirical research. PMID- 2326426 TI - Developmental factors and performance in remedial courses. AB - This study investigated the relations between various developmental factors and performance in remedial courses. The Iowa Developing Autonomy Inventory, Iowa Managing Emotions Inventory, and Iowa Developing Competency Inventory were administered to 231 students enrolled in a developmental studies program at a large state university (enrollment about 25,000). Regression analyses indicated that various developmental measures accounted for a small effect (amount of variance accounted for ranged from 2% to 7%) on performance in remedial courses. The percentage of variance accounted for by the three inventories was similar to what could be accounted for by more traditional measures of SAT scores and high school grade point averages. The percentage of variance accounted for by traditional measures ranged from 2% to 10%. PMID- 2326427 TI - Moonlighting and stress in police officers. PMID- 2326429 TI - Benefits of humor in reduction of threat-induced anxiety. AB - The benefits of humor in reducing anxiety were investigated in a laboratory study, in which subjects were falsely led to believe that they would receive a shock in 12 min. Participants were 53 undergraduate students with either high or low sense of humor as measured by the Situational Humor Response Questionnaire of Martin and Lefcourt (1984). During the anticipatory period, subjects listened to either a humorous tape, a nonhumorous tape, or no tape. Dependent variables were repeated measures of self-reported anxiety, heart rate, and zygomatic facial activity. Anxiety increased over the anticipatory period, as predicted. A significant interaction between condition and time indicated that subjects from the humor condition consistently rated themselves as less anxious and reported less increase in stress as the shock approached. A three-way interaction concentrating on the final 3 min. indicated a tendency for subjects with low sense of humor to have higher heart rates in the no-tape condition than in the humorous or nonhumorous tape conditions. Analysis for zygomatic activity indicated more smiling by subjects with high sense of humor and by subjects in the humor condition. Also, the humorous tape elicited more smiling by subjects with high sense of humor. PMID- 2326428 TI - Locus of control and adjustment to cancer. AB - The English form of the Cancer Locus of Control Scale was administered to an heterogeneous sample of 68 cancer patients. A principal components analysis confirmed the three subscales described in the original Dutch form, however, with five items excluded. Correlations with other measures indicated that high internal control over the course of the illness was associated with a tendency to adopt an attitude toward cancer of 'fighting spirit' whereas high internal control over the cause of the illness was associated with an 'anxious preoccupation' about cancer. No specific relationship was found between scale scores and either depression and anxiety or the tendency to be emotionally controlled. It was concluded that the scale provides a valid measure of perceptions of control of cancer patients and is a useful method of assessing these important psychological responses. PMID- 2326430 TI - Prevalence of sexual assault victimization among heterosexual and gay/lesbian university students. AB - The prevalence of being a victim of forced sex was examined in a sample of 412 university students. Sexual victimization was significantly more common among female than male and among gay and lesbian than heterosexual students. PMID- 2326431 TI - Four-choice win-stay water escape acquisition by rats. AB - Rats were capable of acquiring a four-choice win-stay water-escape task. While preventing access to the incorrect choice sections on information runs affected the first choices made on test runs, it did not affect rate of acquisition. PMID- 2326432 TI - Acute renal failure thirty years on. PMID- 2326433 TI - The influence of visual and tactile inattention on predictions for recovery from acute stroke. AB - Simple screening tests for visual and tactile inattention were used to investigate the influence of perceptual deficits on predictions for the outcome of acute stroke. This influence appeared to be minimal in patients aged over 70 and greatest in younger patients who were incontinent or more severely functionally impaired at the time of the perceptual assessment. When multivariate analysis was used to control for the effects of other prognostic factors, the relationship between visual inattention/hemianopia and functional outcome became very weak, but there was still a significant association with length of stay in hospital. By contrast, even after adjusting for covariates, tactile inattention at one month was still associated with a greater degree of functional impairment at six months. These results could have important practical implications. Poor performance on visuospatial tests may indicate the need for more prolonged rehabilitation rather than predicting failure of recovery. The inclusion of a test for tactile inattention may improve the predictive power of perceptual testing. Further prospective studies are needed to test these hypotheses. PMID- 2326434 TI - Fat absorption and exocrine pancreatic function in human immunodeficiency virus infection. AB - Exocrine pancreatic function and fat absorption were determined using a 'tubeless' test in 25 human immunodeficiency virus (HIV) antibody positive subjects (23 males, two females), CDC criteria groups II (four), III (one), and IV (20). In 12 fat absorption was poor but in only three of these were the results indicative of pancreatic insufficiency and in all three this was mild. In nine of the cases the results were compatible with small intestinal malabsorption. Mild, but not severe, exocrine pancreatic insufficiency may occur in acquired immune deficiency syndrome; however fat malabsorption is more commonly associated with a small intestinal cause. PMID- 2326436 TI - Lung cancer. PMID- 2326435 TI - Antibody-mediated pure neutrophil aplasia, recurrent myasthenia gravis and previous thymoma: case report and literature review. AB - We describe a case of neutrophil aplasia in a woman with recurrent myasthenia gravis and a past history of thymoma. Bone marrow showed virtually absent granulopoiesis but normal erythropoiesis and megakaryopoiesis. Bone marrow cultures showed no growth of granulocyte/mononuclear cell progenitors (CFU-GM). She was treated with immunosuppression including azathioprine, and her neutrophil count returned to normal. Serum before treatment, and also an IgG fraction thereof, inhibited CFU-GM growth both in autologous 'remission' marrow and in allogeneic marrow. She remains in complete remission 36 months after starting azathioprine. This association is extremely rare, and was formerly associated with a grim prognosis. PMID- 2326437 TI - The role of radiologic screening in lung cancer. AB - The present available data do not support the routine utilization of chest radiography or sputum cytology for the early detection of lung cancer. While on an individual basis, as part of a general health maintenance consideration, some high risk individuals may benefit from radiologic or cytologic screening, there has been no overall decrease in cancer mortality associated with these screening procedures. The early cases picked up by screening while asymptomatic and often detected by sputum cytology have lead-time bias to account for prolonged survival. Furthermore, many of these asymptomatic lesions are so indolent that they may never come to the patient's attention during his or her lifetime and the patient may die of other causes. There are other cancers, which may be of the same histology, that develop in the interval between even closely applied screening examinations. Patients with these cancers are often symptomatic and the biologic behavior of these lung cancers is so aggressive that, regardless of intervention, the prognosis is miserable. The cooperative studies also show a fairly high miss rate for the diagnosis of lung cancer even in patients who are being heavily screened. The miss rate for the early detection of lung cancer with chest radiography is probably on the order of 30% or more. That is, in at least 30% of cases, the tumor can be identified retrospectively on earlier examination. Nevertheless, in spite of the significant miss rate, those tumors with an indolent biologic behavior can be present for 2, 3, or more years and still remain localized, have a high resectability rate, and carry a prolonged survival prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326438 TI - Image enhancement using computed radiography. AB - Computed radiography (CR) is emerging as a digital imaging modality for use in conventional radiography. An advantage of CR over film-screen systems is the separation of image acquisition, processing and display. Selection of many different image display characteristics are possible. The system is also able to alter or enhance image details after the radiographic examination has been completed. PMID- 2326439 TI - Sedation of children for CT and MRI scanning. AB - This paper reports on 350 pediatric patients who were studied over a 17-month period to determine the efficacy and safety of oral and intramuscular sedation techniques. The protocol using oral chloral hydrate, 50 mgm/kg, for infants under 1 year of age or intramuscular pentobarbital, 5 mgm/kg, for children over 1 year was found to be an effective, safe and fairly simple approach to pediatric sedation. Of the 350 sedated patients, 343 (98 percent) had satisfactory scans on the same day the examination was scheduled after a single dose or an initial dose and supplementary sedation. PMID- 2326440 TI - A model QA program in radiation oncology. AB - This article presents a detailed and comprehensive technically oriented quality assurance (QA) program for radiation oncology. The primary aspects of care that relate to all departments are included and may serve as a guide for development of criteria and indicators for specialty areas, such as hyperthermia and interoperative radiation. The Joint Commission on Accreditation of Healthcare Organization's (JCAHO) step-by-step process for QA program development is also summarized to clarify the process. PMID- 2326441 TI - Caring for the radiation oncology patient. PMID- 2326442 TI - re: Registry. Can we talk? PMID- 2326444 TI - Technique charts responsibility of users. PMID- 2326443 TI - New effects estimates show danger of radiation. PMID- 2326445 TI - Pursuing excellence in radiologic technology. PMID- 2326446 TI - [Tasks and responsibilities of the editor of a journal]. PMID- 2326447 TI - [A rare mesentericocaval shunt in a case of alpha 1-antitrypsin deficiency]. AB - We report the rare case of a 27-year-old man with decompensated cirrhosis of the liver caused by a deficiency of alpha-1-antitrypsin. The patient was scheduled for liver transplantation. Diagnostic procedures prior to surgery revealed an unusual hepatofugal collateral channel with a marked mesenterico-, lieno-, and renocaval shunt. Since the liver cirrhosis had already been manifest during early infancy, this shunt had formed spontaneously without developing esophagogastric varices. PMID- 2326448 TI - Bronchopulmonary sequestration supplied from the renal artery. AB - In a young lady who was examined for painless hematuria, a normally functioning sequestrated lung was found that was supplied from a branch of the right renal artery. PMID- 2326449 TI - [A comparative study of methods of preparing the colon for a double-contrast study: Prepacol versus ricinus capsules with a cleansing enema]. AB - In a controlled study, we analyzed the efficiency of cleansing out the colon and the best contrast medium of two different regimens (total n = 237) for preparing the colon for double-contrast examination. The recommendations regarding diet and liquid intake, contrast medium and examination technique were identical in both groups. The combination laxative Prepacol without cleansing enema resulted in a more thoroughly cleaned colon that ricinol with cleansing enema (very good/good cleanliness: Prepacol, 92.4%; ricinol, 83.2%, p less than 0.05). However, the quality of contrast medium (good: Prepacol 71.2% as opposed to ricinol 74.8%) was (independent of the preparation method) below standard regarding cleansing of the colon. Better patient compliance was accomplished by Prepacol because the medication was easier to take, and omitting the cleansing enema was a reduction in burden for both patients and medical staff. Written instructions for diet is essential and was of help to the patients. PMID- 2326450 TI - [Colic-like pains. A benign tumor of the small intestine accompanied by invagination]. PMID- 2326451 TI - [Schwannomas of the stomach]. AB - One benign and one malignant schwannoma of the stomach are presented. The gross appearance, degree of local invasion and the complications are demonstrated by double-contrast radiology technique and CT. Benign schwannomas can only be distinguished from the malignant ones on the basis of histological and immunohistochemical criteria. PMID- 2326452 TI - The role of the radiologist in evaluating voiding dysfunction. PMID- 2326453 TI - Professional quality assurance for mammography screening programs. PMID- 2326454 TI - Radiologist and computer: a partnership in clinical radiology for the 1990s? PMID- 2326455 TI - Medical audit of a rapid-throughput mammography screening practice: methodology and results of 27,114 examinations. AB - Medical audit results from the entire experience of a rapid-throughput mammography screening practice are presented, comprising 27,114 examinations conducted from April 1985 to September 1989. The authors screened a self-selected physician-referred population, almost 94% of whom were asymptomatic. Estimated sensitivity of initial mammography interpretation was 93.1% with a specificity of 94.2% and a positive predictive value of 10.0%. Biopsies prompted by screening yielded a diagnosis of malignancy in 32.1% of cases; 170 breast cancers were identified, 67.1% requiring mammographic needle localization. Median cancer size was 12 mm, the rate of axillary nodal metastasis was 11.0%, and the systemic metastasis rate was 1.2%. Of the cancers found, 76.5% were stage 0 or stage 1. Conducting a medical audit is the most convincing way to demonstrate the success of a mammography screening practice, thereby providing this important information for the benefit of screenees, referring physicians, third-party payers, and the personnel who perform the screening. PMID- 2326456 TI - Pulmonary lymphangiomyomatosis and tuberous sclerosis: comparison of radiographic and thin-section CT findings. AB - Chest radiographs, thin-section computed tomographic (CT) scans, and results of pulmonary function tests in nine women with pulmonary lymphangiomyomatosis and two women with pulmonary tuberous sclerosis were retrospectively evaluated. In all patients, CT demonstrated thin-walled cysts less than 20 mm in diameter scattered at random in all parts of the lungs. In eight patients, cysts larger than 20 mm in diameter were also present. Lung tissue between cysts appeared normal in all 11 patients, except one with septal lines and dependent alveolar areas of attenuation. CT showed cysts in three patients whose radiographs were normal, and it demonstrated that many lesions that appeared reticular on plain radiographs were actually cysts. CT findings correlated better with the diffusion capacity of the lungs for carbon monoxide than did the plain radiographic findings. CT was more sensitive and more precise than radiography at showing the presence and morphology of lung abnormalities. PMID- 2326457 TI - Pulmonary lymphangiomyomatosis: correlation of CT with radiographic and functional findings. AB - In 14 patients with biopsy-proved lymphangiomyomatosis, disease extent at computed tomography (CT) was correlated with findings at chest radiography and pulmonary-function testing. The CT scans and chest radiographs were read independently by two chest radiologists. Disease extent was assessed on CT scans by using a visual score (0%-100% involvement of the lung parenchyma) and on radiographs by using an adaptation of the International Labour Office classification of the pneumoconioses. There was good concordance between the two observers for CT and radiographic scores (Kendall tau greater than or equal to .86, P less than .01). A significant but relatively low correlation was present between CT findings and radiographic severity of disease (r = .59, P less than .05). Impairment in gas exchange as assessed with the diffusing capacity correlated better with disease extent seen on CT scans (r = .69) than with chest radiographic findings (r = .59). Three patients had evidence of parenchymal disease on the CT scans but not on the radiographs. In one patient CT findings were negative despite a positive finding on chest radiographs. The authors conclude that CT is superior to chest radiography in the assessment of patients with lymphangiomyomatosis. PMID- 2326458 TI - Lung cancer in patients seropositive for human immunodeficiency virus. AB - The authors describe the clinical and radiographic findings of lung carcinoma in six patients infected with the human immunodeficiency virus (HIV). These patients were in a younger age group than is commonly associated with lung cancer. The radiographic findings included mediastinal adenopathy (n = 5), hilar masses with distal atelectasis (n = 3), parenchymal masses (n = 3), pleural effusions (n = 2), and pleural thickening (n = 1). Recognition of any of these findings should raise the diagnostic possibility of lung cancer in this group of younger patients. PMID- 2326459 TI - Calcified hilar and mediastinal lymph nodes in an AIDS patient with Pneumocystis carinii infection. AB - An unusual radiologic manifestation of Pneumocystis carinii infection (enlarged, calcified hilar and mediastinal lymph nodes) in a patient with acquired immunodeficiency syndrome is described. This atypical manifestation caused significant diagnostic confusion. Recognition that P carinii infection can cause calcification of hilar and mediastinal lymph nodes may prevent this confusion and facilitate diagnosis and treatment. PMID- 2326460 TI - Aortobronchial fistula as a complication of surgery for correction of congenital aortic anomalies. AB - An aortobronchial fistula is a rare condition that is invariably fatal if not diagnosed and surgically treated. Aortic aneurysms, both atherosclerotic and infective, were the main causes in the originally described cases. However, thoracic cardiovascular surgery has recently become the predominant cause. The authors describe two such patients who presented 4 1/2 and 5 years after surgery for the correction of congenital anomalies. Both patients had severe hemoptysis, and angiography helped establish the diagnosis of an aortobronchial fistula. This diagnosis should be considered in patients with hemoptysis and a history of thoracic surgery. PMID- 2326461 TI - Imaging evaluation of children after falls from a height: review of 45 cases. AB - The injury pattern in the child who falls from a height is markedly different from that in the adult, so a different imaging protocol is needed. To help establish such a protocol, the authors reviewed the charts and imaging records of 45 children and infants 12 years of age and younger who had fallen one to six stories. Extremity fractures were the most common injury, occurring in 20 patients. Head injuries (including skull fractures) occurred in 19 patients. Abdominal injuries were present in only one patient. Pneumothoraces were seen in four patients and lung contusions in two patients. Fractures of the pelvis, spine, and os calcis were uncommon. The height of the fall did not enable prediction of either the severity or type of injury. The authors recommend radiography of the cervical spine and chest alone in the initial evaluation of the injured child and greater willingness to obtain computed tomographic (CT) scans of the head in children than in adults. Radiographs of the pelvis, thoracolumbar spine, and lower extremities, as well as CT scans of the head and abdomen, should be obtained on a case-by-case basis, and not according to protocol, as is often the situation in adults. PMID- 2326462 TI - Continual NMR cardiography without gating: M-mode MR imaging. AB - A magnetic resonance (MR) pulse sequence was designed and implemented to examine the heart continually without gating, at rates in excess of 256 images in 7 seconds. The results are analogous to those of M-mode ultrasound, allowing interactive exploration of cardiac dynamics and flow in real time with full three dimensional freedom of view. The technique is based on designed two-dimensional excitation pulses in which the magnetic field gradient is not constant, as in section-selection pulses, but varies in time to define a trajectory that results in a specified (eg, cylindric) region of excitation. The technique was implemented on a 1.5-T clinical imager with no special hardware and was tested on phantoms and volunteers. In human subjects, details of valve motion, intracardiac flow, and wall motion could be observed from moment to moment along optimal lines of sight selected interactively, with or without flow compensation and without gating. The momentary physiologic changes in chamber volumes and blood pool replenishment that occur during rhythm disturbances, the Valsalva maneuver, and simple breathing and breath-holding were readily demonstrated. PMID- 2326463 TI - CT-angiographic correlation of collateral venous pathways in isolated splenic vein occlusion: new observations. AB - The computed tomographic (CT) findings in 18 patients with angiographically proved, isolated splenic vein occlusion (SVO) were retrospectively analyzed. The distribution of venous collateral vessels and the frequency of their occurrence in these patients were then compared with CT findings in 17 patients with proved portal hypertension and normal CT findings in 20 patients. Short gastric and coronary collateral vessels were seen in 61% and 83%, respectively, of patients with SVO and in 71% each in patients with portal hypertension. However, a large gastroepiploic vein was seen only in patients with SVO (11 of 18 patients [61%]). Recanalization of umbilical/paraumbilical veins was seen only in patients with portal hypertension (seven of 17 patients [41%]). Results suggest that collateral vessels in SVO often have a characteristic and distinctive appearance on abdominal CT scans. PMID- 2326464 TI - Peripheral arterial occlusive disease: P-31 MR spectroscopy of calf muscle. AB - The effect of a graded exercise protocol on phosphorus-31 magnetic resonance (MR) spectroscopy of calf skeletal muscle in nine healthy (control) subjects and 16 patients with symptomatic peripheral arterial occlusive disease (PAOD) was assessed. Ankle-brachial pressure indexes were obtained in all 16 patients, and 10 patients underwent peripheral arteriography. Temporal profiles of pH and the inorganic phosphorus (Pi) index were calculated from the spectra. A Pi-index recovery rate constant was calculated for each subject. Arteriograms were graded by calculating the runoff resistance in the limb of interest. The pH profiles during exercise did not differ significantly between the PAOD patients and control subjects. The Pi-index recovery rate constant in the PAOD patients was significantly (P less than .01) smaller than in the control subjects. There was no significant correlation between recovery rate and the ankle-brachial pressure indexes, but there was a strong negative correlation between recovery rates and angiographic resistance grades, with smaller recovery rate constants in patients with increased arterial resistance. It is concluded that P-31 MR spectroscopy shows promise as a direct measure of tissue perfusion. PMID- 2326465 TI - Status of admitting privileges for university-affiliated diagnostic radiology departments. AB - Members of the Society of Chairmen of Academic Radiology Departments (SCARD) from 135 university hospitals in Canada and the United States were surveyed regarding their experience in admitting patients to diagnostic radiology departments between 1986 and 1989. One hundred departments (74%) replied; of these, 33 departments (33%) admitted patients during 1989. From 1986 to 1989 the percentage of diagnostic radiology departments admitting patients rose from 20% to 33%. Forty-one departments had admitting privileges, and nine departments had applied for admitting privileges. The remaining 50 departments were content to admit patients to medical and/or surgical services or had no interest in obtaining admitting privileges. The rapid growth of noncardiac interventional procedures, the obvious benefit to patients whose disease is manageable with imaging-guided therapy, the increasing interest of nonradiologists in performing interventional radiologic procedures, and the potential financial benefits to the hospital that are associated with short patient stays provide incentive for diagnostic radiologists to admit patients for cardiovascular and interventional procedures. PMID- 2326467 TI - Bronchial artery embolization to control hemoptysis in cystic fibrosis. AB - Severe hemoptysis in cystic fibrosis can be life-threatening because of acute blood loss or because it interferes with sustaining physical therapy of the chest. Hemoptysis was controlled in 19 of 20 cystic fibrosis patients by means of embolization with a combination of 250-590-microns particles of polyvinyl alcohol foam and absorbable gelatin pledgets. Repeat embolization was needed in eight patients to achieve or maintain effective hemostasis. One or more aberrant bronchial arteries were found in seven patients (35%), and a spinal artery branching from a vessel that also supplied bronchial circulation was present in 11 patients (55%). The data suggest that although embolization has a wider applicability than previously reported, care should be taken during angiography to evaluate the bronchial circulation because aberrant bronchial vessels and spinal arteries arising from bronchial circulation are common. PMID- 2326466 TI - Fibrinolytic therapy for upper-extremity arterial occlusions. AB - Acute upper-extremity arterial occlusion may be due to embolic phenomena or de novo thrombosis. If the occlusion is left untreated, claudication or ischemia necessitating amputation can occur. Operative Fogarty-balloon embolectomy has been the treatment of choice for this entity. In a 6-year period the authors used fibrinolysis on nine occasions in eight patients to treat acute upper-extremity arterial occlusions. Concomitant balloon angioplasty was helpful in four cases. Success, defined as a normal hand with at least one artery that was continuously patent to the wrist, was achieved in all patients. A single significant groin hematoma was seen. Neither stroke nor death occurred in any case, and no amputations were necessary. Local transcatheter intraarterial administration of urokinase can be considered a first-line treatment for brachial artery embolus and other causes of acute upper-extremity arterial occlusion. PMID- 2326468 TI - Embolization of large saccular aneurysms with Gianturco coils. AB - In five patients embolization of large saccular aneurysms involving the popliteal artery, common carotid artery, arch of the aorta, and abdominal aorta was performed with custom-designed spring coils. Surgery was attempted before embolization for the aneurysm involving the popliteal artery. The other aneurysms were considered nonresectable due to their critical location. Although maximal packing of the aneurysmal sac was attempted, delayed follow-up angiography revealed displacement of the coils away from the parent vessel as well as further expansion of the residual aneurysmal sac. In these cases complete embolization of the aneurysmal sac was not possible without obstructing the parent artery. PMID- 2326469 TI - Orbital lymphangiomas: clinical, radiologic, and pathologic characteristics. AB - To assess the value of computed tomography (CT) in evaluation of orbital lymphangioma, the CT findings in 11 patients were retrospectively analyzed and correlated with the clinical, hemodynamic, surgical, and pathologic findings. The lesions were classified by location in three categories: superficial (n = 1), deep (n = 6), or combined (n = 6); the latter were evident earlier in life. The CT findings correlated well with the surgical and histologic findings. Orbital lymphangiomas were poorly defined lesions that crossed anatomic boundaries such as the conal fascia and orbital septum. Some degree of enhancement was the rule, ranging from scattered patchy areas to enhancement of the majority of the lesion. Areas of hemorrhage caused cystlike masses with rim enhancement. Preoperative identification of the vascular enhancing component at CT examination enables the surgeon to resect this area to prevent postoperative hemorrhage. High-resolution CT is of great value in the diagnosis and preoperative treatment planning of orbital lymphangioma. PMID- 2326470 TI - Prominent meningeal enhancement adjacent to meningioma on Gd-DTPA-enhanced MR images: histopathologic correlation. AB - To assess tissue changes responsible for enhancement of the meninges adjacent to meningiomas on magnetic resonance (MR) images, the authors correlated the MR imaging characteristics of meningeal lesions seen before and after administration of gadolinium diethylenetriamine-pentaacetic acid (DTPA) with the appearance of these lesions on contrast material-enhanced computed tomographic (CT) images and with histopathologic findings in four patients. Histopathologic examination of meninges showed increased loose connective tissue, hypervascularity, and dilated vessels. There was neoplastic infiltration of the dura mater in two patients but it was restricted to the immediate junction of neoplasm and dura mater, with maximum peripheral extension within 1 mm of the tumor margin. In both patients the meninges were enhanced far beyond the neoplastic infiltration. The other two patients showed no infiltration of dura mater. These findings suggest that pathologic enhancement of meninges adjacent to meningioma after administration of Gd-DTPA mainly represents reactive changes to the neoplasm and does not necessarily indicate neoplastic involvement. PMID- 2326471 TI - Intracranial vascular lesions: optimization and clinical evaluation of three dimensional time-of-flight MR angiography. AB - The clinical value of three-dimensional time-of-flight magnetic resonance (MR) angiography was prospectively evaluated in 26 patients with congenital intracranial vascular lesions; 12 had arteriovenous malformations (AVMs), and 14 had venous angiomas. In the initial phase of the study the entire region of interest was imaged with one large acquisition volume (60-120-mm-thick slab). Later, the angiograms were obtained with adjacent but slightly overlapping, 30-mm thick slabs, which clearly improved vascular detail. Gadolinium enhancement slightly improved depiction of veins but not of arteries. MR angiograms were compared with available conventional angiograms and MR studies. The topography of the AVM nidus was equally well appreciated on the MR as on the conventional angiograms. However, in six of 12 patients the hyperdynamic afferent arteries were incompletely shown on MR angiograms because of incomplete rephrasing. In three patients, venous drainage was also incompletely visualized. Compared with conventional MR studies, MR angiography offered the same detection rate but better anatomic insight. Thirteen of the 14 venous angiomas were also identified on MR angiograms. Detailed imaging, however, necessitated gadolinium enhancement and thin-slab acquisition. PMID- 2326472 TI - Esophageal fistulas associated with mycobacterial infection in patients at risk for AIDS. AB - Although opportunistic infections of the esophagus occur commonly in acquired immunodeficiency syndrome (AIDS), inflammation is generally limited to the mucosal surface. During a 7-month interval, six men at risk for AIDS underwent barium esophagography because of persistent symptoms of esophageal disease. In each case, transmural inflammation of the esophagus was found (esophagomediastinal communication in three cases and esophagobronchial fistulas in three cases). Two patients had an esophagoesophageal fistula, an inflammatory lesion that has not, to the authors' knowledge, been previously described with mycobacterial infection. Mycobacterial infection was documented by means of culture findings in all six patients (Mycobacterium tuberculosis in five, M avium in one). In three cases mycobacteria were either seen in or cultured from esophageal biopsy specimens. The finding of deep esophageal ulceration, intramural dissection, or fistula formation in a patient with AIDS should suggest the diagnosis of esophageal tuberculosis. PMID- 2326473 TI - Iodinated contrast medium as an aid to gallstone dissolution with methyl tert butyl ether: in vitro study. AB - Methyl tert-butyl ether (MTBE) floats on bile, whereas gallstones sink. Therefore, stones and MTBE are separated by a layer of bile. This study investigates the effect of contrast medium on flotation of gallstones in bile and its role in stone and fragment dissolution with MTBE. Fresh human gallstones, both calcified and noncalcified, from different patients were tested in vitro for flotation in bile, with and without addition of contrast medium. All gallstones or fragments sank in bile before the introduction of contrast medium. Noncalcified stones floated when the contrast medium-bile volume ratio was 1:6 or more, while double this amount of contrast medium was required to float calcified stones. Fragments did dissolve somewhat in MTBE in the presence of bile alone, but when contrast medium was added, almost complete dissolution occurred. This is thought to be due to increased contact between the fragments and MTBE, both floating on the contrast medium-bile mixture. Contrast material may be a useful adjuvant in gallstone dissolution therapy with MTBE in vivo. PMID- 2326474 TI - Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. AB - An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm. The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular transport and through interendothelial junctions. Twenty-four hours after intravenous administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (d) the magnetic moiety in organ-targeted superparamagnetic contrast agents for magnetic resonance imaging. PMID- 2326476 TI - Cauda equina syndrome complicating ankylosing spondylitis. AB - The cauda equina syndrome is an uncommon and poorly understood complication of ankylosing spondylitis. The clinical and radiologic findings in five patients with this syndrome are described. Typical findings include cutaneous sensory impairment of the lower limbs and perineum with sphincter disturbances. Motor impairment occurs less frequently, and associated pain is an inconstant feature. Enlargement of the caudal sac and dorsal arachnoid diverticula that erode the lamina and spinous processes are characteristic myelographic and computed tomographic findings. The pathogenesis of the cauda equina syndrome in ankylosing spondylitis remains unknown but may be due to demyelination, post-irradiation ischemia, or compression from spinal arachnoiditis. PMID- 2326475 TI - Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. AB - An ultrasmall superparamagnetic iron oxide (USPIO) preparation was evaluated as a potential intravenous contrast agent for lymph nodes. Relaxation time measurements and magnetic resonance (MR) imaging were performed in rats with normal lymph nodes and in rats with lymph node metastases. In normal animals, lymph node relaxation times decreased maximally within 24-48 hours after intravenous administration of USPIO. Twenty-four hours after administration, the T2 of normal lymph nodes had decreased from 74 msec +/- 2.2 to 30 msec +/- 0.7 (USPIO, 40 mumol of iron per kilogram) or 15 msec +/- 0.0 (200 mumol Fe/kg), whereas the T2 of metastatic nodes did not change. MR imaging of the animal model of nodal metastases confirmed the hypothesis that intravenously administered USPIO decreases signal intensity of normal but not metastatic nodes. A single intravenous administration of USPIO may allow detection of nodal metastases on the basis of signal intensity characteristics rather than the currently used, insensitive size characteristics. PMID- 2326477 TI - Rheumatic disease of the temporomandibular joint: MR imaging and tomographic manifestations. AB - Thirty-six temporomandibular joints (TMJs) in 28 symptomatic patients (aged 14-40 years) with rheumatic disease (mostly rheumatoid arthritis) were studied with magnetic resonance (MR) imaging and hypocycloidal tomography. MR images of four TMJs were normal. Another four TMJs showed internal derangement. Of the 28 TMJs presumed to show rheumatic disease involvement (26 with condylar destruction or deformation), 23 showed abnormal disk structure--five showing severe disk destruction and 18 showing less severe abnormalities (inhomogeneous structure, fragmentation, poor delineation, and severe flattening). MR images showed bone abnormalities in 27 of the 36 TMJs, and tomography showed abnormalities in 25 of the 36 TMJs. Good agreement between the two imaging modalities regarding surface irregularities was found. However, MR imaging demonstrated more extensive bone abnormalities than did tomography in 11 TMJs. The potential of MR imaging for depicting bone and soft-tissue abnormalities associated with rheumatic TMJ involvement was clearly demonstrated. PMID- 2326478 TI - Core decompression for avascular necrosis of the femoral head: correlation between long-term results and preoperative MR staging. AB - A long-term radiographic follow-up study was conducted on 24 patients (34 hips) who underwent core decompression of the femoral head for avascular necrosis (AVN). The purpose of the study was to assess the potential correlation between the extent of AVN, as determined with preoperative magnetic resonance (MR) imaging, and development of collapse. The preoperative MR results were classified into four categories: group A, no AVN; group B, less than 25% involvement of the weight-bearing portion of the femoral head; group C, 25%-50% involvement; and group D, more than 50% involvement. Histologic evidence of AVN was found in all 34 hips. Collapse occurred in none of the hips in groups A and B (n = 12), in three of seven hips (43%) in group C, and in 13 of 15 hips (87%) in group D. It is concluded that MR estimation of the extent of femoral head involvement with AVN may help in predicting which femoral heads will collapse shortly after core decompression, so that this invasive procedure can be avoided in patients at risk. PMID- 2326479 TI - Spinal bone mineral density measured with quantitative CT: effect of region of interest, vertebral level, and technique. AB - This study documents the relationship between different vertebral bone compartments with quantitative computed tomography (CT). Four distinct patient groups were investigated: healthy pre- and early postmenopausal women as well as healthy and osteoporotic late postmenopausal women. Three different regions of interest (ROIs) were employed: the elliptical ROI located in the anterior trabecular portion of the vertebral body, the peeled ROI of irregular shape that circumscribes most of the trabecular bone, and the integral ROI including all bone except for the transverse processes. Both single- and dual-energy quantitative CT techniques were employed at T-12 through L-3. Correlation between measurements in the elliptical and peeled ROIs was high (r = .985). The authors concluded that either ROI is acceptable for clinical use. The decrements in bone mineral density (BMD) for the integral ROI were smaller than those for the elliptical ROI. Dual-energy measurements were consistently higher than single energy measurements. BMD as a function of vertebral level decreased systematically from T-12 to L-3. However, the average density of T-12 through L-3 can be accurately predicted by the average density of L-1 and L-2 (r = .997). Precision did not deteriorate significantly when BMD was expressed as the average of L-1 and L-2 (1.5%) instead of T-12 through L-3 (1.4%). In this study the data suggest a modified quantitative CT protocol for clinical applications in which BMD of only L-1 and L-2 are measured at a fixed gantry tilt. PMID- 2326480 TI - Steady-state free precession imaging in the presence of motion: application for improved visualization of the cerebrospinal fluid. AB - The authors discuss the appropriate FISP (fast imaging with steady-state precession) sequence structure to maintain constant phase at the radio-frequency pulse in the presence of motion. They present preliminary results of its application to head and spine imaging in an effort to maintain contrast between the cerebrospinal fluid (CSF) and the soft tissue. In the usual application of these FISP-like sequences, the gradient structure is modified to avoid unwanted signal (and contrast) variations due to field inhomogeneities. This change makes the signal sensitive to motion with a resulting decrease in signal intensity for moving tissue. The expected high contrast at large flip angles for tissues with low T1/T2 ratios such as CSF is not obtained. The technique discussed here overcomes the effects of field inhomogeneities and compensates for moving spins so that the transverse steady-state equilibrium and hence high contrast are obtained simultaneously. PMID- 2326481 TI - A detector for scanned projection radiography. AB - A solid-state electronic x-ray detector, the multilinear array (MLA), was developed for general-purpose digital overhead radiography (DOR). The image sensor of the MLA consists of an x-ray phosphor affixed to approximately 29,000 photodiodes. The image sensor is rectangular (35.2 cm X 1.05 cm) and is designed for scanned projection imaging with a 1.05-cm-thick fan beam. The MLA incorporates charge-coupled device circuitry that performs time-delay integration of the photocharge. The MLA is installed in a prototype DOR system that generates a 35.2-cm X 35.8-cm image with a 2,014 X 2,048 12-bit image matrix and 0.175-mm pixels. The scan time per image is 7 seconds, and the exposure time of any given point of a patient is 0.21 seconds. Operational principles of the MLA are described, performance measurements presented, and images acquired with the prototype DOR system shown. The MLA has an exposure latitude of 333:1 10% modulation transfer function response at 1.8 cycles per millimeter, 15% detector detective quantum efficiency (DQE) at 60 keV, and 78% scatter DQE under high scatter imaging conditions. DOR images of a contrast-detail phantom are superior to those produced by conventional medium-speed screen-film radiography. PMID- 2326482 TI - Evaluation of the susceptibility effect on the phase images of a simple gradient echo. AB - The phase shifts of a simple gradient echo (fast low-angle shot) were correlated with the local change in resonance frequency due to the differences in susceptibility among tissues (susceptibility effect). Susceptibility effects were considered theoretically, and the phase shifts for spherical and cylindrical configurations were calculated. A 1.5-T magnetic resonance unit and phantoms filled with solutions of copper chloride in water were used to obtain the phase images. The phase shifts of the simple gradient echo coincided with the values calculated with use of the sum of the macroscopic magnetic field and the cavity field of Lorentz. The authors conclude that the gap of the phase shifts at interfaces of tissues is useful in the evaluation of differences in magnetic susceptibility among tissues. PMID- 2326483 TI - Stage T1 glottic carcinoma: results of radiation therapy or laser excision. AB - A retrospective analysis was made of the data on 60 patients with stage T1 glottic carcinoma (43 T1a, 17 T1b) who received radiation therapy and 17 patients with T1a disease who underwent laser excision as the primary treatment modality. Patients who received radiation therapy achieved 3- and 5-year actuarial local control rates of 92% and 89% for T1a and 77% and 77% for T1b disease, respectively. In patients who underwent laser excision (all with T1a disease), the 3-year local control rate was 77%. Of the 42 evaluable irradiated T1a patients, 31 (74%) had a normal to near-normal voice, eight (19%) had mild or intermittent hoarseness, and three (7%) had persistent hoarseness. Of the 13 evaluable patients in the laser-excision group, four (31%) had a normal to near normal voice, five (38%) had mild or intermittent hoarseness, and four (31%) had persistent hoarseness. The difference in the quality of voice between these two groups is statistically significant (P = .012), although the ultimate local control rate after salvage therapy for irradiated patients (97%) was similar to that for laser-excision patients (94%). PMID- 2326484 TI - Diagnostic radiology around the world. AB - The frequency and type of radiographic examinations performed, as well as the type and quantity of radiographic equipment currently available, vary from country to country, depending on the type of screening programs used and on the level of health care available. These factors are a reflection of the country's overall wealth and stage of development. In past years, the annual number of radiologic examinations performed has increased worldwide, and this trend is expected to continue. If less developed countries are unable to increase their radiologic capacity at least as quickly as their population increases, they will fall further behind in their ability to care for their citizens. PMID- 2326485 TI - Burns associated with clinical MR examinations. PMID- 2326486 TI - Wrist arthrography. PMID- 2326487 TI - Eddy-current-induced artifacts caused by an "MR-compatible" halo device. PMID- 2326488 TI - Associative strength effects in the lexical decision task. AB - Four experiments explore the role of automatic and attentional processing in producing strength effects in a lexical decision task. Experiment 1 manipulated the relative proportion of related and unrelated pairs, the stimulus-onset asynchrony (SOA), and the strength of the prime-target relationship. Results indicated that strength was independent of the proportion of related and unrelated pairs and SOA. Experiment 2 manipulated the relative proportion of strong and weak related pairs and the strength of the prime-target relationship at a relatively long SOA interval (500 msec). Results showed that the strength effect was present when more strong than weak pairs were presented, and it was absent when the stimulus list contained more weak than strong pairs. Experiment 3 replicated the more weak pairs condition of Experiment 2 but with a short SOA interval (100 msec) and showed that the strength effect was found regardless of the large number of weak related pairs presented. Experiment 4 manipulated strength of the prime-target relationship and proportion of strong and weak pairs but introducing a neutral prime condition and a longer SOA interval (1000 msec). Results are discussed within a two-process model (Posner & Snyder, 1975) postulating that the strength effect at short SOAs is due to automatic processes, whereas at long SOAs it is due to the influence of attentional processes. PMID- 2326489 TI - The processing of non-target words: semantic or not? AB - It is known that people reacting to visual words may be affected by the meaning of accompanying non-target words. On the approach to perception developed by Treisman (e.g. 1986), this is surprising, because meaning might be thought to require analysis of conjunctions of physical features and so should remain uncomputed for non-target words. Treisman's approach does, however, assert that analysis of the target may unleash further processes that would prime the system for detection of related words. If this were so, then presentation of the target earlier than the distractors would increase the effect of the latter; whereas if analysis of non-targets were independent of priming, they might be expected to have a smaller effect when delayed. Further, if the sets of words involved are small and familiar, then individual features of primed non-targets, rather than conjunctions of features, might trigger interference. They might especially do so when spatial separation of target and non-target is small. Five experiments using a paradigm developed by Shaffer and LaBerge confirm that the meaning of non target words affects response to targets; but (1) this is more true for early than for late arrival of the target; (2) it is affected by target/non-target separation in space; (3) it is true for familiar sets of repeated words but not, in these data, for words used once only in the experiment. It is therefore concluded that the results are more consistent with a Treisman type of explanation than with a theory of universal and automatic full analysis. PMID- 2326490 TI - How do readers know where to look next? Local information distributions influence eye fixations. AB - Skilled readers' eye movements were recorded as they inspected sentences in preparation for comprehension questions. The sentences were written around target words that had uneven distributions of information, in that the words were predictable, given either the first few letters or the last few letters. Some parts of these words can be described as being more important than others for successful word recognition, and the experiments asked whether inspection patterns reflect the uneven distributions. Four types of ten-letter word were used: words with highly redundant endings (e.g. engagement), with moderately redundant endings (e.g. repatriate), with moderately redundant beginnings (e.g. superstore), and words with informative beginnings and endings (e.g. amalgamate). Redundancy was defined operationally in terms of the number of possible completions of a word given the first few or last few letters. A highly redundant ending is therefore one that occurs frequently and cannot be used to identify the word. Words gaining just one fixation received this fixation nearer to the word's centre than in the case of the first fixation upon words gaining two fixations. The single fixation also had a longer duration, giving support to the notion of a convenient viewing location, which, when achieved, can lead to a net saving in inspection time. In the case of words with redundant endings gaining just one fixation, the fixation was nearer to the beginning of the word than in the case of words with informative endings, and this influence of word type upon the location of the first fixation was interpreted in favour of the parafoveal processing hypothesis of eye guidance during reading. PMID- 2326491 TI - Age differences in working memory tasks: the role of secondary memory and the central executive system. AB - Two experiments are reported in which age differences in working memory performance are explored. In the first study, young and older adults held 2, 3, 4, or 5 unrelated words in mind while verifying a single or complex sentence. An age-related decrement was found in subsequent serial recall of the words, and this decrement was larger with longer word lists. Experiment 2 confirmed the interaction between age and list length, using list lengths of 4, 6, and 8 words and a free-recall procedure. There was no interaction between age and divided attention in either experiment. Surprisingly, sentence complexity had a greater detrimental effect on recall in the younger group. The results are discussed in terms of articulatory rehearsal being augmented by using secondary memory in the case of younger subjects. PMID- 2326492 TI - Hemisphere-specific resource demands of task expectancies. AB - The hemisphere-specific resource demands of expecting letter- and figure-matching tasks were investigated, using dual-task methodology. Matching task expectancies were induced by blocking trials with respect to stimulus type (letters or geometrical figures). On one third of the trials, the matching stimuli were unexpectedly omitted. The secondary task required a speeded reaction to a laterally presented auditory probe. The side of probe presentation was unpredictable. Probe reaction times were taken as an index of the resource demands imposed by the primary task on the contralateral hemisphere. For both the trials with and without matching stimuli, probe reaction times showed a significant interaction between lateral side of probe presentation and block type (letters or figures). When letters were expected, reaction times were slower in the left-hemisphere probe task. Probe reaction times were equally fast for both sides when figures were expected. Overall, these results indicate that task expectancies primarily demand resources from the hemisphere that is specialized for carrying out the expected task. PMID- 2326493 TI - Selective transfer of responding in conditional discriminations. AB - In each of three experiments rats received discrimination training in which whether or not a 10-sec target stimulus was followed by food was signalled by a 2 min background stimulus. In the first experiment the target was paired with food in the presence but not the absence of the background stimulus. Subsequent tests revealed that the background elevated responding to a target that had taken part in a similar discrimination. However, it had no influence on the responses elicited by a partially reinforced conditioned stimulus. In the remaining experiments the target was paired with food in the absence but not the presence of the background. Test trials then revealed that although the background had an inhibitory influence on the responses elicited by a target from a similar discrimination, it had no influence on the responses elicited by either a partially or a continuously reinforced conditioned stimulus. Various explanations for this selective influence of a background stimulus are considered. PMID- 2326494 TI - A demonstration of observational learning in rats using a bidirectional control. AB - Hungry rats observed a conspecific demonstrator pushing a single manipulandum, a joystick, to the right or to the left for food reward and were then allowed access to the joystick from a different orientation. The effects of right-pushing vs left-pushing observation experience on (1) response acquisition, (2) reversal of a left-right discrimination, and (3) responding in extinction, were examined. Rats that had observed left-pushing made more left responses during acquisition than rats that had observed right-pushing, and rats that had observed demonstrators pushing in the direction that had previously been reinforced took longer to reach criterion reversal and made more responses in extinction than rats that had observed demonstrators pushing in the opposite direction to that previously reinforced. These results provide evidence that rats are capable of learning a response, or a response-reinforcer contingency, through conspecific observation. PMID- 2326495 TI - Auditory food cue conditioning: effects of spatial contiguity and taste quality. AB - The effects of spatial location of an auditory stimulus and quality of a potentiating taste on the aversive conditioning of an auditory food cue were investigated. In Experiment 1 rats ate salty food activating a tone from a speaker either in (spatially contiguous with) or displaced from the food and were then made ill. It was found that spatial contiguity during conditioning resulted in avoidance of food with a contiguous or a displaced tone in testing, and spatial displacement during conditioning resulted in avoidance of food only if the tone was also displaced in testing. Experiment 2 was identical, except rats ate salty, bitter, or sweet food with a displaced tone during conditioning and testing. The salty and bitter food groups demonstrated an avoidance of noisy food relative to the sweet food group. These results indicate that spatial contiguity interacts with taste quality in the conditioning of nongustatory food cues. PMID- 2326496 TI - Chlordiazepoxide and the moderation of the initial response to reward reduction. AB - The effectiveness of chlordiazepoxide (CDP) in reducing negative contrast on the first day after a shift from 32% to 4% sucrose was investigated in four experiments using rats. Previous studies indicated that CDP was effective on the second, but not on the first postshift day. In Experiments 1 and 1a, neither initial experience (3 or 10 days) with the eventual postshift 4% solution (i.e. 4%, then 32%, then 4%), nor initial experience with alternating 4% and 32% sucrose, led to a reliable contrast-reducing effect of CDP on the first shift day. Evidence from Experiments 2 and 3 suggested that a range of doses of CDP (3, 5, 10, and 15 mg/kg) did not have reliable effects on the first postshift day, although the two lower doses did reduce contrast on the second postshift day (the higher doses were not administered on Day 2). The evidence suggests that the relative ineffectiveness of CDP in moderating the initial response to reward reduction is not related to a problem of recognizing the difference between the postshift solution and the memory of the preshift solution. Alternative interpretations in which CDP's lack of effect on the initial occurrence of contrast is related to an initial stage of unconditioned frustration and/or exploratory behaviour are considered. PMID- 2326497 TI - Distribution of calcitonin gene-related peptide and calcitonin-like immunoreactivity in trout. AB - Radioimmunoassay and chromatography were used to study the occurrence of calcitonin gene-related peptide in various tissues of the rainbow trout, Salmo gairdnerii. The highest concentrations of the peptide were found in gill (1.68 +/ 0.09 ng/mg protein) and in intestine (1.06 +/- 0.4 ng/mg protein). Significant concentrations were also found in heart and stomach. The level in brain was very low. In trout, the plasma concentration accounted for 283 +/- 82 pg/ml. Chromatographic analysis of the calcitonin gene-related peptide (CGRP)-like immunoreactivity occurring in gills showed that two molecular forms cross-reacted with the anti-human CGRP antibody, one co-eluting with the synthetic human CGRP. In addition, calcitonin in fish is not confined to the ultimobranchial organ but is also present in organs as heart, intestine, kidney, spleen and stomach. The evidence of CGRP in fish emphasizes the role of this hormone in evolution and leads us to investigate its physiological role in this species. PMID- 2326498 TI - Significance of gastric endocrine tumor and age-related gut peptide alterations in Mastomys. AB - The Mastomys (Praomys natalensis) species are a unique natural model in which the bioactivity of gastric carcinoids may be studied. Several investigators have previously demonstrated that these tumors contain large amounts of histamine. In this study we investigated the presence of peptides associated with the neoplasm. The levels and location of gastrin, gastric inhibitory peptide (GIP), neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), glucagon, bombesin, vasoactive intestinal peptide (VIP) and somatostatin (SRIF) were investigated by radioimmunoassay and immunocytochemistry. In addition the distribution of these peptides were evaluated in the gastrointestinal tract of young and old animals to investigate possible age-related changes. PYY and enteroglucagon (EG) were significantly (P less than 0.001) elevated in both tumor tissue (676 +/- 152, 551 +/- 164 pmol/g) and plasma (620 +/- 160, 500 +/- 147 pmol/l) of tumor-bearing animals. Immunocytochemistry revealed PYY- and EG-like immunoreactivity in 20-30% of tumor cells. A significant decrease (P less than 0.05) in bombesin was noted in older animals, but no changes in gastric tissue content of PYY or EG could be detected between young and old animals. Gastrin was not detected in tumors and there were no significant changes in tissue or plasma levels with age. Small bowel concentrations of VIP and PYY were higher in the older mastomys (P less than 0.05). In contrast, colonic levels of bombesin, VIP, somatostatin and PYY were significantly lower (P less than 0.05) in older mastomys compared with young. The age-related changes in several peptides may reflect an adaptive response to acid hypersecretion. The multi-hormonal character of these neoplasms suggests that these tumors develop from a pluripotential stem cell. PMID- 2326499 TI - Mechanism of inhibitory action of peptide YY on cholecystokinin-induced contractions of isolated dog ileum. AB - In isolated canine ileal longitudinal muscle preparations, cholecystokinin octapeptide (CCK-8) produced a concentration-dependent contraction, which was suppressed by peptide YY (PYY) and was abolished by tetrodotoxin and atropine. PYY was approximately 2200-times as potent as CR1505, a CCK-receptor antagonist. PYY opposed the action of CCK-8 to a greater extent than that of nicotine and transmural electrical stimulation. Acetylcholine-induced contractions were not influenced by PYY. It seems likely that the CCK-8-induced ileal muscle contraction is associated with an activation of CCK receptors in cholinergic nerves, which generates nerve action potentials and releases acetylcholine, whereas CCK-8 acts on CCK receptors in gallbladder smooth muscle, producing contractions. It may be concluded that PYY inhibits the action of CCK-8 on ileal muscle strips, by inhibiting the release of acetylcholine from cholinergic nerve terminals. On the other hand, in the gallbladder, PYY does not appear to block cholinergic nerve function. PMID- 2326500 TI - Chloroquine alters the processing of secretin in isolated rat pancreatic acinar cells. AB - In this study we considered the effect of chloroquine on the processing and intracellular distribution of internalized secretin radioligand in acinar cells. Chloroquine (100 microM) had no effect on the total amount of 125I-secretin bound but had marked effects on the processing of this radioligand in acinar cells. After an initial 60 min of radioligand binding in the presence and absence of chloroquine, cells were washed free of unbound radioligand, resuspended and then processed for different times at 37 degrees C. During 60, 120 and 180 min of processing, the amount of internalized radioligand in the presence of 100 microM chloroquine was increased by 116, 194 and 273%, respectively, compared to untreated control samples. Chloroquine also increased the amount of intact 125I secretin radioligand within the cell as measured by rebinding to pancreatic plasma membranes. After 120 and 180 min of processing, intact peptide within the acinar cell was 25 and 66% greater in the presence of this agent than in control samples (P less than or equal to 0.01). To determine if chloroquine affected intracellular localization of the secretin radioligand, we measured the amount of radioactivity in soluble and particulate fractions of cell homogenates. Chloroquine decreased radioactivity entering particulate fractions of the cell by greater than 35% after 120 and 180 min of processing (P less than or equal to 0.01). This study demonstrates that (1) chloroquine inhibits the intracellular degradation of secretin in acinar cells and (2) chloroquine alters intracellular localization of this peptide during processing. PMID- 2326501 TI - Do normal plasma neurotensin concentrations increase ileal output? AB - Infusions of neurotensin increase ileal secretion in experimental animals, and the volume of ileal effluent in patients with ileostomies. The aim of the present study was to determine whether normal postprandial plasma concentrations of neurotensin increase the volume of fluid leaving the ileum. Basal and peak postprandial plasma neurotensin concentrations were 23 (17-36) and 39 (25-43) pmol/l (median and range) respectively in five subjects with ileostomies and 15 (3-27) and 32 (15-82) pmol/l respectively in nine normal subjects. Infusion of neurotensin for 30 min at a rate of 6.3 pmol/kg/min into six patients with ileostomies increased ileostomy output about 10-fold, and produced a significant decrease in the concentration of solid material, but plasma neurotensin concentrations rose to 237 (82-422) pmol/l during infusion at this rate. Infusion of neurotensin at 2.3 pmol/kg/min, producing plasma levels of 60 (16-108), had no significant effect the amount or nature of ileostomy effluent. We conclude that normal postprandial plasma concentrations of neurotensin are unlikely to influence the volume of fluid leaving the ileum. PMID- 2326502 TI - Effects of neuropeptide Y and noradrenaline on uterine artery blood pressure and blood flow velocity in the pregnant guinea-pig. AB - Neuropeptide Y (NPY) coexists with noradrenaline (NA) in many peripheral sympathetic nerves. Since it has been found that patients with preeclampsia have elevated myometrial levels of both NPY and NA, we have examined the effects of NPY and NA on blood pressure and blood flow velocity in the uterine artery of the term pregnant guinea-pig (n = 7). We found that NPY (10-1000 pmol) significantly increased local blood pressure, with increases ranging from 15.4% (P less than 0.05) to 46.4% (P less than 0.001) as compared to control. NA (10-1000 pmol) had similar effects, increasing local blood pressure (5%-57.5% (P less than 0.01]. NPY had no significant effect on uterine blood flow velocity as measured by pulsed Doppler ultrasound, whereas NA (10-1000 pmol) decreased local uterine blood flow velocity (5.9%-30.2% (P less than 0.05]. The effect of NPY on blood pressure was phentolamine-resistant, indicating that it is not alpha-adrenoceptor mediated. The results indicate that NPY and NA have significant pressor effects in the local uterine circulation during pregnancy in the guinea-pig. PMID- 2326503 TI - Evidence that gastrin enhances 45Ca uptake into bone through release of a gastric hormone. AB - An acute challenge with gastrin-17 enhanced the uptake of 45Ca into sternum and several long bones in rats by about 10-30%; gastrectomy prevented this effect. Long-term treatment with (Leu15)-gastrin-17 (continuous infusion via osmotic minipumps for 4 weeks) enhanced the uptake of 45Ca into bone (examplified by radius and sternum) by 18-26% (tested on the last day of the infusion). Surgical removal of the acid-producing part of the stomach (fundectomy) or treatment with the anti-ulcer drugs, ranitidine (a histamine H2-receptor antagonist administered by continuous infusion) or omeprazole (an H+/K(+)-ATPase inhibitor administered daily by gastric tube for 4 weeks), induced sustained hypergastrinemia (through loss of acid feedback inhibition of gastrin release). The ranitidine- and omeprazole-evoked hypergastrinemia was associated with 32-62% enhancement of bone 45Ca uptake but the hypergastrinemia of fundectomized rats was not. Gastrectomy abolished the effect of omeprazole. We suggest that exogenous and endogenous gastrin influences calcium uptake into bone indirectly by releasing a calciotropic hormone (gastrocalcin) from the acid-producing part of the stomach. The bone ash weight was reduced by gastrectomy or fundectomy (4 weeks), but neither ranitidine nor omeprazole-evoked hypergastrinemia (4 weeks) raised the bone ash weight. The stimulated calcium uptake into bone of hypergastrinemic rats treated with ranitidine or omeprazole was associated with a 22-32% increase in the density of osteoclasts in the tibia. This finding is in line with the hypothesis that long-lasting hypergastrocalcinemia produces accelerated turn-over of bone rather than increased bone calcium content. PMID- 2326504 TI - Sensitivity of spontaneously hypertensive and of Wistar Kyoto rats to the antidipsogenic action of eledoisin. AB - This study investigated the sensitivity of spontaneously hypertensive rats (SHR) and of Wistar Kyoto rats (WKR) to the antidipsogenic action of the tachykinin eledoisin (ELE). Drinking was evoked by: (a) intracerebroventricular (i.c.v.) injection of angiotensin II, (b) subcutaneous (s.c.) administration of hypertonic NaCl (1.5 M; 1 ml/100 g b.wt.) or (c) 18 h of water deprivation with free access to food. In accordance with previous studies, the dipsogenic effect of all three treatments was exaggerated in the SHR. And when treated with i.c.v. ELE (12.5-25 ng/rat) they were far less sensitive than WKR to its antidipsogenic action on angiotensin-induced drinking. Smaller differences in strain sensitivity were also observed for the effect of ELE on cell dehydration- and on water deprivation induced drinking, but only at the dose of 200 and 50 ng/rat, respectively. The different sensitivity of the SHR to the antidipsogenic effect of ELE supports the idea that tachykininergic mechanisms for control of water intake are differently regulated in the SHR than they are in the normotensive WKR. PMID- 2326505 TI - Tonic suppression of baroreceptor reflex by endogenous neurotensin in the rat. AB - We evaluated the modulatory role of endogenous neurotensin (NT) in baroreceptor reflex (BRR) response in Sprague-Dawley rats anesthetized with pentobarbital sodium. Intracerebroventricular (i.c.v.) administration of NT (15 or 30 nmol) significantly reduced the sensitivity of the BRR response. Blocking the endogenous activity of the tridecapeptide with its specific antagonist, (D-Trp11) NT (4 or 8 nmol) or antiserum against NT (1:20); or inhibiting the aminopeptidases with bestatin (200 nmol), on the other hand, promoted a potentiation of BRR response. When administered together with bestatin (200 nmol), the suppressive effect of NT (15 nmol) on the BRR response was further enhanced, as was the augmentative action of (D-Trp11)-NT (4 nmol). Upon microinjection into the bilateral nucleus tractus solitarius (NTS), NT (600 pmol) and (D-Trp11)-NT (150 pmol) respectively elicited a reduction and enhancement of the BRR response. These results suggest that neurons that contain NT may participate in central cardiovascular regulation by tonically suppressing the BRR, possibly via an action on the NTS where baroreceptor afferents terminate. PMID- 2326506 TI - Bombesin-like immunoreactive material in the gut, and the effect of bombesin on the stomach circulatory system of an elasmobranch fish, Squalus acanthias. AB - The distribution, nature and amount of bombesin-like immunoreactivity (IR) in the gastrointestinal canal and its afferent vessels was investigated in the spiny dogfish (Squalus acanthias) together with the in vitro effect of synthetic bombesin on perfusion flow through the vascularly perfused dogfish stomach. Nerve fibres showing bombesin-like IR frequently occurred in the walls of the anterior mesenteric and coeliac arteries and the intrinsic vessels of the gut. Chromatographic studies revealed that multiple peaks of bombesin-like IR material were present in extracts of the spiny dogfish gastrointestinal vessels. Bombesin like IR was also present in muscle and mucosal layers of the gut with higher levels in muscle compared with mucosa, and higher levels in the stomach than in the intestine and the rectum. Exogenous bombesin increased the flow through the vasculary perfused spiny dogfish stomach in a dose-dependent manner. Studies with tetrodotoxin and atropine showed that bombesin probably exerts its effect directly on the vascular musculature. It is concluded from this study that bombesin-like material is present in nerves innervating the gut circulatory system of the spiny dogfish. Bombesin may affect the blood-flow to the gastrointestinal canal, possibly via a direct effect on vascular smooth muscle. PMID- 2326507 TI - [Leakage radiations in a medical electron accelerator facility--calculation of neutron doses in the facility]. AB - Neutron doses often come dominant in mazes of electron accelerator facilities in which X-rays of energies more than 10 MV are produced. A simple analytical method to calculate neutron doses in such a facility is developed. In the calculation procedure, it is assumed that the irradiation room is spherical in shape and the maze is cylindrical. Multiple reflection of neutrons is also considered using the albedo concept in the calculation. The procedure allows to exist a hanging wall over the entrance of the irradiation room and also multiple legs in the maze. All the parameters used in the calculation are given definitely in the procedure, and any experiment is unnecessary to determine value of the parameters. Comparison of the calculated results with experimental ones will be described in the following report. PMID- 2326508 TI - [Leakage radiations in a medical electron accelerator facility--measurement of neutrons and comparison with calculation]. AB - Neutron dose equivalent rates are measured in the irradiation room and the maze of a medical electron accelerator facility. An m-counter used for measurement is associated with a gate circuit to reject piled up signals caused by pulsed X rays, so that it is possible to measure the neutrons without obstruction by the piled up signals even in the irradiation room. Counting loss of neutrons is mathematically corrected, and the correction factor comes nearly equal to 1.5 at dose points close to the entrance to the irradiation room when 14 MV X-rays are generated. The measurement in the maze agrees with the calculation reported in the preceding report in a factor less than 1.5 except for dose points close to the entrance to the irradiation room. PMID- 2326509 TI - [Shielding ability of lead loaded radiation resistant gloves]. AB - The shielding ability of radiation resistant gloves was examined. The gloves are made of lead loaded (as PbO2) polyvinyl chloride resin and are about 0.4 mm in thickness (70 mg/cm2). Eleven test pieces were sampled from each of three gloves (total 33) and the transmission rates for radiations (X-ray or gamma-ray) through the test pieces were measured with radiation sources, 99mTc, 57Co, 133Ba, 133Xe and 241Am. The differences of the transmission rates for radiations by the positions of the gloves were smaller than 15%, and the differences by three gloves were smaller than 5% in the case of 60 keV and 141 keV radiations. The average transmission rates for radiations in the 33 test pieces were about 40% for 30 keV radiation, about 90% for 80 keV and 140 keV radiations. The shielding characteristic of the gloves is equivalent to about 0.026 mm thick lead plate. PMID- 2326510 TI - [Concrete plan for routine check-up of rotational axis shift and image size variation in SPECT system. Subcommittee for Standardization of Radionuclide Imaging, Medical and Pharmaceutical Committee: Japan Radioisotope Association]. PMID- 2326511 TI - [Equipment and instruments for use in radiological protection. X. Recent development and problem of radiation protection dosimetry (1)--External radiation dosimetry for X.gamma-rays and beta-rays]. PMID- 2326512 TI - Acquired immunodeficiency syndrome: correlation of radiologic and pathologic findings in the brain. AB - The appearance on magnetic resonance (MR) and computed tomographic (CT) images of specific central nervous system disorders associated with acquired immunodeficiency syndrome in 12 cases was correlated with autopsy findings. There were three cases of human immunodeficiency virus (HIV) encephalopathy; three, primary lymphoma; three, toxoplasmosis; one, cryptococcosis; one, cytomegalovirus infection; and one, progressive multifocal leukoencephalopathy. MR imaging demonstrated the various cranial lesions more clearly than did CT. On the basis of MR imaging characteristics, HIV encephalopathy could be distinguished from other lesions, particularly progressive multifocal leukoencephalopathy. Basal ganglia were the most common sites of involvement in opportunistic infections and primary lymphoma. Reliable distinguishing features among lesions of the basal ganglia were not found, except for cryptococcal lesions, which had a unique appearance. PMID- 2326513 TI - Quantitative computer-aided analysis of lung texture in chest radiographs. AB - The authors describe a computerized method to quantify and characterize interstitial diseases by using physical texture measures obtained from an analysis of the power spectrum of lung textures in digital chest radiographs. They compared these texture measures obtained from standard radiographs from the International Labour Office (ILO) classification scheme and the ILO classification categories for small opacities in pneumoconioses. Their preliminary results indicate that texture measures obtained from this computer analysis of the ILO standard radiographs correspond closely with the ILO classification categories. PMID- 2326514 TI - Object radiography contrived to illustrate basic principles. AB - To add variety to radiologic teaching and to lower view box monotony, we imaged ordinary objects in circumstances that illustrate--caricature might be a better word--basic pathologic and radiologic principles. We tried to make each object image an interpretation challenge amenable to solution through logical application of such principles, and the result has added spice to our teaching sessions. Yet object radiography can play only an ancillary teaching role; we use it sparingly and always in combination with cases that illustrate the principles in question. Otherwise, the technique itself may add to the monotony it is designed to combat. PMID- 2326515 TI - Case of the day. Mixed oligodendroglioma. PMID- 2326516 TI - Case of the day. Appendicitis with appendiceal rupture and pelvic abscess. PMID- 2326517 TI - [Bibliometry, authorship and scientific ethics]. PMID- 2326518 TI - [Systemic absorption of 2% lidocaine from the lumbar epidural space]. AB - The curves of lidocaine (LDC) plasma levels versus time were evaluated in a group of 16 patients receiving single epidural injections of 2% LDC for each metamer to be anesthesized. LDC absorption from epidural space is fairly rapid (tmax = 17 +/ 4 min and t1/2a = 6.2 +/- 1.7 min). This results in very shape peak plasma levels (2.97 +/- 0.87 micrograms/ml with 2% LDC). The remaining pharmacokinetic parameters were: Ke = 0.0057 +/- 0.0022 min-1 and Vd = 1.5 +/- 0.5 l/kg. In all patients adequate levels for operation were obtained. PMID- 2326519 TI - [Effects of postoperative pain on lung volume in patients undergoing aortic surgery]. AB - To evaluate the potential advantages of the administration of extradural morphine to control postoperative pain and its effects on respiratory function, 39 patients were randomly assigned to one of two groups before aortic surgery. The first group (20 patients) received intravenous analgesia as required (control group). The second group (19 patients) received extradural morphine in a programmed fashion. During the immediate postoperative period the following parameters were measured in both groups: respiratory rate, vital capacity, peak expiratory volume in the first second, PaO2, PaCO2, arterial pH, heart rate, and systolic and diastolic blood pressure. In the group treated with morphine the postoperative increase in heart and respiratory rate was significantly smaller than in the control group (p less than 0.01). Postoperative forced pulmonary volumes were higher in the morphine group (p less than 0.01). However, there were no differences in time of hospitalization between both groups. There were more complications in the control group, but the difference did not reach statistical significance. PMID- 2326520 TI - [Localization of lumbar epidural space by loss of resistance and using the Episensor: a comparative study]. AB - Since the existence of negative pressure in the epidural space was reported, its technique of localization has undergone changes directed to improve objectivity, reliability and safety. The aim of the present study was to evaluate a new electronic divide to localize the epidural space, i.e. the Episensor (Palex, Spain). To this end, 71 patients, both males and females, undergoing elective urological surgery and in whom catheterization of the lumbar epidural space had been planned, were prospectively evaluated and randomly assigned to two homogeneous groups. In group I (n = 35) the epidural space was localized by the classical technique of loss of resistance, while in group II the Episensor was used. In both groups several technical parameters, the qualification of the operator and the complications of the procedure were evaluated. There were no significant differences between both groups regarding the quality of epidural blockade or the subjective technical difficulty of the operator. The incidence of complications of the technique of puncture was significantly higher in group II (p less than 0.05); the most common were dura mater puncture in 13 group II patients and in one group I patient (p less than 0.001). There was no correlation between the qualification of the operator and the development of complications. It was concluded that the use of Episensor to localize lumbar epidural space did not improve the effectiveness of blockade but increased the iatrogenic effects of the puncture. Our lack of experience with this new technique and the low negative pressure of lumbar epidural space might have been the causes of the poor results, that we consider as initial in the evaluation of this new method. PMID- 2326521 TI - [Pheochromocytoma: review of the preoperative treatment and anesthesiologic technic in 14 patients]. AB - Fourteen patients operated for pheochromocytoma from 1978 to 1988 are reviewed. The preoperative treatment with adrenergic blockers is analyzed: phenoxybenzamine with final doses of 10-140 mg/day (mean 55.4 mg/day) and propranolol with doses of 40-80 mg/day (mean 50 mg/day). The premedications and anesthetic techniques are compared, the use of droperidol being discouraged because of the development of hypertensive paroxysms both preoperatively and postoperatively. The new benzodiazepines are offered as an alternative. The treatment of hypertensive paroxysms with phentolamine with total doses of 2.5-35 mg and that of peroperative arrhythmias with propranolol with total doses of 1-6 mg are reported. The recently described therapeutic approaches are also discussed. PMID- 2326522 TI - [Severe heart arrhythmia secondary to magnesium depletion. Torsade de pointes]. AB - We report a case of torsade de pointe ventricular tachycardia in a patient with chronic magnesium depletion. The etiological aspects implicated this unusual cardiac arrhythmia are: the congenital long QT syndrome; bradycardia, either sinusal or due to atrioventricular block; ionic depletions: hypokalemia, hypocalcemia and hypomagnesemia; treatment with antiarrhythmic class AI drugs (quinidine-like agents), tricyclic antidepressants, phenothiazines and erythromycin; organophosphate poisoning. After ruling out other factors, we concluded that it was caused by hypomagnesemia on the basis of laboratory findings and the good response to replacement therapy. We then discuss the several types of therapy proposed for this arrhythmia; finally, we emphasize the major role of magnesium in myocardial repolarization. PMID- 2326523 TI - [Tracheal injury during transhiatal esophagectomy without thoracotomy. Anesthesiologic management]. AB - A patient with carcinoma of the lower third of esophagus suffered an extensive tracheal tear during transhiatal esophagectomy without thoracotomy, with severe impairment of ventilatory and hemodynamic status. A right thoracotomy was required for the repair of the tracheal lesion, which extended to the origin of left bronchus. During the maneuvers for bronchial intubation, the hypoxia worsened and cardiac arrest caused by ventricular fibrillation appeared. The arrhythmia was reverted. Operative mortality of transhiatal esophagectomy without thoracotomy is 8%. Pneumothorax is the most common operative complication. Tracheal laceration is reported in 1% of cases; usually it is not severe and is easily treated, although it can have significant severity and result in death as in the present case. After the operation, the patient persisted hemodynamically unstable, developing a new gasometric deterioration and bilateral pleural effusion, with impairment of coagulation. The patient died 39 hours after operation. The anesthetic management of peroperative tracheal tear is reviewed. PMID- 2326524 TI - [The method of the "hanging drop" in interpleural analgesia]. PMID- 2326525 TI - [Intravenous regional anesthesia with ketamine]. PMID- 2326526 TI - [Spinal microsurgical catheterization causes fibrosis]. PMID- 2326527 TI - [Digital photoplethysmography as evaluation method of the effectiveness of locoregional blocks]. PMID- 2326528 TI - [Application of Episensor for detecting the interpleural space]. PMID- 2326529 TI - [Changes in blood calcium during liver transplant in children]. AB - We have evaluated the changes in plasma total and ionic calcium levels in twenty hepatic transplantations in pediatric patients. Direct intraoperative monitoring of ionic calcium is fundamental, because its variability is unrelated with total calcium levels; in addition, normal ionic calcium levels contribute to the hemodynamic stability of the patient. Although at the end of the operation total and ionic calcium levels were similar to the postinduction measurement, their values were dissociated in the perianhepatic period. In the anhepatic phase ionic calcium reached its lowest value (1.00 mmol/l) although total calcium increased above postinduction level from 2.13 to 2.46 mmol/l (p less than 0.05). In hepatic transplantation in pediatric patients calcium administration is indicated during the transfusion of citrated blood, being particularly necessary during the anhepatic phase to prevent ionic hypocalcemia. PMID- 2326530 TI - [Aortico-left ventricular tunnel. Presentation of 2 new cases. Usefulness of non invasive study]. AB - In the last years the anatomic characteristics of the left aorto-ventricular tunnel and the clinical aspects of this uncommon malformation have been well described. Its evolution usually fatal without surgical procedure is in great contrast with the slight symptoms encountered by us in two new cases. This particular finding joined to the specific aspects found in the noninvasive color Doppler study, have lead us to present two new cases of left aorto-ventricular tunnel successfully operated. PMID- 2326531 TI - [Restrictive myocardiopathy caused by endomyocardial fibrosis]. AB - Endomyocardial fibrosis, an uncommon condition, is the most important cause of restrictive cardiomyopathy. Etiology of endomyocardial fibrosis is unknown, but evidence continues to accumulate that a close connection exists between eosinophilia and endomyocardial disease. Patients with this condition respond poorly to medical treatment, and survival is only for a few months or years when late stage heart disease is present. Surgery is nowadays recommended in these cases. A marked eosinophilia was found in a 58 years old woman that was admitted to the hospital because of a severe congestive cardiac insufficiency. Two dimensional echocardiographic study and typical angiographic appearance suggested the presence of endomyocardial fibrosis. Endocardectomy and mitral valvular replacement were performed. PMID- 2326532 TI - [Mitro-aortic endocarditis caused by Listeria monocytogenes]. AB - A case of Listeria monocytogenes valvular endocarditis is reported. This patient required mitral and aortic valve replacement by Bjork-Shiley mechanical prostheses. Patient clinical condition was progressively deteriorated, affecting the left ventricular function, increasing the size of vegetations and the presence of aortic annular abscess. This case represents the 48th reported in the literature and the third in our country. We here comment about the clinical aspects and the treatment of this infrequent entity. PMID- 2326533 TI - [Endocarditis caused by Coxiella burnetii in aortic prosthesis. Presentation of a case with a fatal course]. AB - A case of endocarditis caused by Coxiella burnetii in a patient with an aortic Starr-Edwards prosthesis is described. The diagnosis was made by detecting high titres of antibody against Coxiella burnetii phase I antigens. After 15 weeks of chemotherapy with tetracycline and cotrimoxazole, aortic prosthetic valve replacement was carried out because of haemodynamic deterioration and he died 4 days later. The histologic picture of the excised valve was consistent with endocarditis. Coxiella burnetii should be considered in the differential diagnosis of culture-negative endocarditis in our country, especially when the patient has not receiving antibiotic treatment in the last 2 weeks. PMID- 2326534 TI - [Aortic subvalvular annular aneurysm after closed thoracic traumatism. Presentation of a case]. AB - A case of a 29 year old man with congenital aortic stenosis who developed a subvalvular annular aneurysm of the left ventricle after being run by a car is presented. At surgery his aortic valve was replaced and the opening of the aneurysm was closed with a patch of Dacron. Due to the dense adhesions to the aorta and left atrium no attempts were made to excise the sac, that was not compromising the dynamics of any one of these structures. PMID- 2326535 TI - [Long-term results in patients with tricuspid prosthesis]. AB - A retrospective study was undertaken of 31 patients submitted to tricuspid valve replacement between 1977 and 1988, either alone or associated to mitral or aortic replacement. The cause of the tricuspid lesion was rheumatic in 19 patients, congenital in seven, prosthetic valve thrombosis in two and miscellaneous in the remaining 3 patients (endocarditis, carcinoid syndrome, iatrogenic operative tricuspid regurgitation). Of the 31 tricuspid prostheses reviewed, 26 were mechanical (St Jude, Bjork-Shiley) and five of the biological type (Ionescu, Hancock). Results showed that 25% of patients died in the hospital; 75% of them had been operated previously. With a follow-up averaging 3.9 years the complications related with the prosthesis were: thrombosis of the tricuspid prostheses in 1 patient (1.2% patients-year) and hemolytic anemia in another. Ninety percent of patient included in the follow-up were in NYHA class I or II. Three patients (14%) died due to a cause not directly related to the prosthesis. An actuarial analysis showed intrahospital survival rates of 55%, 100% and 75% in patient with 3, 2 and 1 prostheses, respectively; at 6 months postoperatively the figures were 55%, 87% and 75%, and at a follow-up of 3 years, 55%, 67% and 66%. In conclusion, in patients submitted to a tricuspid valve replacement mortality is high before hospital discharge, and is related to the clinical situation. A sustained improvement is observed in survivors once discharged, independently of the number of prostheses implanted. Complications related to the tricuspid prosthesis are comparable to those observed with prostheses in mitral or aortic position. PMID- 2326536 TI - [Prognostic significance of silent ischemia in the exercise test in patients with coronary disease]. AB - To evaluate the prognostic significance of silent ischemia during exercise testing, 152 consecutive patients (143 males, 9 females) with a mean SD of 55 +/- 7 years (age range 32-73) who underwent exercise testing and coronary arteriography within 3 months were studied. All patients had the following characteristics: 1) a positive electrocardiographic exercise test response; 2) significant coronary artery disease on the arteriography; 3) uninterrupted clinical follow-up for a minimum of 6 months. The 152 patients were divided in 2 groups: group I: 56 patients (37%) with ischemic ST-segment depression during exercise testing without angina (silent ischemia); group II: 96 patients (63%) with ischemic ST-segment depression and angina (symptomatic ischemia). Patients in group I and group II showed similar time to ST-segment depression (3.6 +/- 1.5 min vs 3.2 +/- 1.4 min; p = NS), maximal ST-segment depression and peak heart rate-systolic pressure product (21,151 +/- 7,124 vs 20,456 +/- 6,024; p = NS). Exercise duration was longer in group I than in group II (5.6 +/- 2.1 min vs 4.8 +/- 1.5 min; p less than 0.001). The extent of coronary artery disease defined by the number of significant narrowed coronary vessels, left ventricular end diastolic pressure and ejection fraction were similar in the 2 groups. Sixty six patients who underwent coronary bypass surgery were not included in the analysis. The remaining 86 patients (40 in group I and 46 in group II) were medically treated. The mean follow-up period was 43,5 +/- 25 months (range 6-101).2+ myocardial ischemia during exercise testing. PMID- 2326537 TI - [Chronic stimulation thresholds using carbon and platinum electrodes]. AB - Low-output pacemaker programming depends on the absolute value of the chronic pacing threshold. To assess the chronic threshold with three different types of leads we have used Siemens-Vario pacemakers which allow us to measure the chronic voltage threshold noninvasively. Forty six patients had a 12 mm2 platinum tip lead; 38, 12 mm2 carbon tip lead an 15, 9 mm2 carbon tip lead (Siemens, 414-415, 412 and 423). Platinum leads longevity was 45 +/- 15.9 months; 12 mm2 carbon tip leads, 28 +/- 6.5 and 9 mm2 carbon tip leads, 17 +/- 4.5. Forty two months postimplantation chronic threshold (measured at 0.5 msec pulse-width) was 1.6 +/- 0.6 V for platinum electrodes and 1 +/- 0.3 V for 12 mm2 carbon tip leads (p less than 0.001). Twenty four months postimplantation 9 mm2 carbon electrodes chronic threshold was 1 +/- 0.4 V, and 1.7 +/- 0.5 V for platinum electrodes (p less than 0.001). There were no differences between carbon tip leads with 9 and 12 mm2 pacing area. The new activated carbon tip leads have lower chronic pacing thresholds than platinum electrodes with the same pacing area. Pacemaker-patients with these new type of leads can benefit of reduced output programming and increase their pacemaker longevity. PMID- 2326538 TI - [Comparative study of iohexol and iopamidol as cardioangiographic contrast media]. AB - We have done a double-blind randomized study to compare the cardiac effects of 2 nonionic low osmolality contrast agents, iohexol (n = 25) and iopamidol (n = 25), for left ventriculography and coronary arteriography. No statistical differences were detected between both groups in quality of image, clinical (absence of nausea; intense warmth [8% vs 8%, p = NS]) and electrocardiography (repolarization changes [24% vs 12%, p = NS], absence of severe bradycardia and ventricular arrhythmia) effects. Ventriculography induced no change in systolic left ventricular pressure (iohexol: 128.6 +/- 18 vs 127 +/- 19 mmHg, p = NS; iopamidol: 133 +/- 24 vs 131.8 +/- 23 mmHg, p = NS), and a little but significant rise in left ventricular end-diastolic pressure (iohexol: pre = 11.6 +/- 7 vs post = 13.9 +/- 7 mmHg, p less than 0.01; iopamidol: 11.7 +/- 4 vs post = 15.5 +/ 5 mmHg, p less than 0.001). Our results suggest that iohexol and iopamidol are comparable and qualified for angiocardiography. PMID- 2326539 TI - [Calculation of the mitral valve area using Hatle's method. Effect of the preload change induced by nitrates]. AB - The aim of the present study was to assess the effect of changes in preload induced by nitrates on calculated mitral valve area by Doppler pressure half time. Forty patients (mean age 51 +/- 10 years), 23 with mitral stenosis, ten with mechanical prosthesis and seven with bioprosthesis were studied by Doppler echocardiography. Twelve were in sinus rhythm and 28 had atrial fibrillation. Mitral valve area by Doppler pressure half-time, peak and mean mitral gradient and pulmonary artery systolic pressure were measured before and after isosorbide dinitrate (5 mg) or nitroglycerin (0.4 mg). The nitrates produced a significant reduction of pre-load in total group (p less than 0.001) but did not change the mitral valve area (1.9 +/- 0.8 to 1.9 +/- 0.8). The subsets of patients with size valvular area (greater than 2 cm2, less than 2 cm2, less than 1.5 cm2, mechanical prosthesis, bioprosthesis, sinus rhythm and atrial fibrillation) had an insignificant change in mitral valve area after administration of nitrates. We conclude that the mitral valve area by Doppler pressure half-time method do not modify in different conditions of preload. These findings remain in patients with prosthesis, different sizes of mitral valve area and atrial fibrillation. PMID- 2326541 TI - Immunologic mechanisms in neurologic and psychiatric diseases. PMID- 2326540 TI - [Mortality and survival in total anomalous pulmonary venous drainage]. AB - The results in the management of 36 cases of isolated total anomalous pulmonary venous connection are presented. This patients are the 1.55% of the 2,322 children diagnosed of congenital heart disease by catheterization and angiography in our hospital at the 1971-1988 period. Nineteen had a type I, five a type II, eight a type III and four a mixed type lesion. The total mortality rate was 63.8%. Twenty six infants underwent surgical correction at a mean age of 2.5 months with an operative mortality rate of the 57.7%. Eleven infants survived operation. There have been no late deaths but one children developed stenosis at the anastomosis. The final actuarial survival rate was the 34.4% in the total group and the 42.3% in the operated group. The strongest determinants of survival were the type of lesion and pulmonary venous obstruction. No improving in the total and the surgical results has been observed in the last 10 years. PMID- 2326542 TI - Clinical and subclinical involvement of the central nervous system in systemic lupus erythematosus. PMID- 2326543 TI - Enhancement of cisplatin toxicity by buthionine sulfoximine, a glutathione depleting agent, in mice. AB - Pretreatment of buthionine sulfoximine (500 mg/kg, i.p., BSO), a potent glutathione-depleting agent, markedly increased the lethality and nephrotoxicity of cisplatin. These results suggest that a reactive electrophilic intermediate may be involved in the mechanism of cisplatin nephrotoxicity and moreover, that renal glutathione may play a protective role against cisplatin-induced nephrotoxicity. PMID- 2326544 TI - Liver changes induced in the hamster by steroids. AB - Groups of mature female Syrian golden hamsters were injected s.c. with peanut oil solutions of estradiol benzoate and progesterone at daily dosages of 10 micrograms and 20 mg, respectively, the controls receiving the vehicle. The male series comprised controls and estrogen-treated. A portion of each group was injected i.p. with phenobarbital at 80 mg/kg daily for the last 3 days and all animals were sacrificed on day 10. Hepatic microsomal total protein, cytochrome P 450 and enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase of the steroid-injected groups revealed no definite changes over the controls except for an increase in the hydroxylase activity with the progesterone group. In general, cytochrome P-450 and the enzyme activities were significantly elevated on comparison of the phenobarbital-injected groups versus the uninduced controls. Inter-group comparisons of the phenobarbital-injected females revealed no remarkable changes over the respective controls, but with the males, the hydroxylase activity of the estrogen-treated group was markedly elevated. In contrast to the rat, the hamsters injected with estrogen at the specified dosage, underwent no significant change in the liver weight percentages. However, liver enlargement occurred with progesterone as such or on phenobarbital treatment in comparison with the corresponding control groups. PMID- 2326545 TI - Hemodynamic effects of a potassium ionophore, lonomycin A. AB - Lonomycin A, an ionophorous antibiotic, exhibits a high transport rate for monovalent cations, especially potassium. The cardiovascular actions of lonomycin A were studied in anesthetized dogs. Lonomycin A administered intravenously at 30 micrograms/kg increased coronary blood flow slightly with relatively small alterations in other hemodynamic parameters. After 100 micrograms/kg, a slight and transient fall followed by an increase in blood pressure was observed. Coronary blood flow, cardiac output, left ventricular pressure, max dP/dt, and isometric ventricular segmental tension increased. Arterial venous O2 difference and total peripheral vescular resistance decreased. Above 300 micrograms/kg, dramatic alterations were produced in almost all hemodynamic parameters, and total peripheral vascular resistance was increased. Lonomycin A-induced positive inotropic action was partly inhibited by pretreatment with pindolol, however gradual shortening of the ventricular wall length was still observed. A positive chronotropic action induced by lonomycin A was inhibited by pindolol pretreatment in vivo. On the other hand, lonomycin A elicited a negative chronotropic effects in the isolated guinea-pig right atrium, concomitantly increasing resting tension. These results suggest that lonomycin A alone produces peripheral vascular dilation and effects cardiac functions, which are in turn modified by lonomycin A-induced cathecholamine release from nerve terminals. PMID- 2326546 TI - Synthesis and pharmacological evaluation of acyl derivatives of phenelzine. AB - Acyl derivatives of phenelzine were required for pharmacological evaluation. Eight mono- and di-acyl derivatives were synthesized and characterized by gas chromatography, mass spectrometry, nuclear magnetic resonance and infrared spectrophotometry. Selective acylation was observed with both acetic anhydride and ethyl chloroformate. In aqueous medium, monoacylation yielded N1-acetyl- and N1-(ethoxy-carbonyl)-phenelzine exclusively, whereas in non-aqueous medium only N2-acetyl and N2-(ethoxycarbonyl) products were obtained. NMR temperature studies were conducted to ascertain the presence of rotational isomers and their ratios. At room temperature, one ethoxy-carbonyl and four phenelzine acetate derivatives were present as mixtures of rotamers. Preliminary evaluations of the MAO inhibiting properties of acylated phenelzines indicate that a hydrogen atom on the N1-position of phenelzine and its derivatives is essential for activity. PMID- 2326547 TI - Function and localization of high and low affinity binding sites to muscarinic receptors in longitudinal and circular smooth muscles of human stomach. AB - The contractile response to acetylcholine (ACh) and the binding of [3H] quinuclidinyl benzilate [( 3H]QNB) to muscarinic receptors in both longitudinal and circular muscles were examined in fundus, body and antrum of human stomach which was obtained by surgical operation for gastric cancer or ulcer. The values of pD2 and pA2 for ACh and atropine, respectively, on longitudinal muscle of fundus were similar to those of body but were larger than those of antrum. On the other hand, the values of pD2 and pA2 on circular muscles were not different among fundus, body, and antrum and were similar to those on longitudinal muscle of antrum. By Scatchard analysis of receptor binding of [3H]QNB in homogenate, at least two subclasses of binding sites, i.e. high and low affinity sites, were observed in fundus and body, while only high affinity binding site was found in antrum. Thus, we conclude that there are at least two subclasses of muscarinic receptors which regulate the contraction of smooth muscle in different regions of human stomach. PMID- 2326548 TI - Research on heterocyclic compounds. XXVI. Antiinflammatory and related activities of some 2-phenylimidazo[1,2-b]pyridazines. AB - Five acidic phenyl derivatives of the imidazo[1,2-b]pyridazine system were subjected to some tests in vivo in order to evaluate their biological activity. Antiinflammatory activity was studied by means of the carrageenin rat paw edema, whereas writhing induced in mice by acetic acid was used to assess analgesic activity. The irritative and ulcerogenic action on the rat gastric mucosa was examined after oral administration of larger doses. The inhibitory activity on platelet malondialdehyde production was studied in vitro. The experimental results are discussed from the point of view of structure-activity relationships and mode of action. PMID- 2326549 TI - Ketoconazole-induced hepatic lysosomal phospholipidosis: the effect of concurrent barbiturate treatment. AB - An unusual hepatic phospholipidosis produced by repeated high doses of ketoconazole in the mouse was investigated. This abnormal phospholipid accumulation was dose dependent after seven days of daily oral treatment over a 150-350 mg/kg ketoconazole dose range. The accumulation continued after 21 days at the 250 mg/kg dose level. Ultrastructural and biochemical studies revealed that ketoconazole produced a hepatic lysosomal accumulation of concentric lamellar bodies, as typically produced by many cationic amphiphilic drugs. Ketoconazole administered orally in mice at 250 mg/kg also induced total hepatic protein, microsomal protein, cytochrome p-450, and ethylmorphine N-demethylation. Concurrent phenobarbital and ketoconazole administration appeared to further increase hepatic drug metabolizing parameters and to reduce the extent of the hepatic phospholipid accumulation. PMID- 2326550 TI - Induction and immunohistochemical localization of cytochrome P-450 PCN by non steroidal compound, in rat liver microsomes. AB - Induction of cytochrome P-450 PCN (P-450 PCN) by non-steroidal compound, M79193 (cyclohexane spiro-2,6-chloro-1'-(3-dimethyl-aminopropyl) spiro(chroman-4,4' imidazolidine)-2',5'-dione], was investigated in both sexes of rats. The immunohistochemical localization of P-450 PCN was also studied in liver lobules of untreated and M79193-treated male rats. Immunoblot analysis of rat liver microsomes with anti-P-450 PCN indicated that the amount of P-450 PCN increased 5 to 7-fold by the treatment with M79193, but no increase was observed in P-450 PB 1 (P450IIB1) or P-450 MC-1 (P-450IA1). P-450 PCN was uniformly distributed in liver lobule of untreated rats, and was significantly increased by the treatment with M79193 in both the periportal and pericentral regions of the lobules. PMID- 2326551 TI - Some properties of the viroid inducing peach latent mosaic disease. AB - Analysis by polyacrylamide gel electrophoresis of nucleic acid extracts from different peach samples, healthy or infected with the peach latent mosaic (PLM) disease, demonstrated the association of this disease with an RNA exhibiting the electrophoretic properties typical of circular viroid molecules. This RNA was called peach latent mosaic viroid (PLMV), since a purified preparation of it, when inoculated into GF 305 peach seedlings induced characteristic symptoms of PLM disease. PLMV was estimated to have a molecular size in the range of 330-340 bases, by comparison of its electrophoretic mobility under denaturing conditions with those of several viroid RNA. Dot-blot analysis showed that PLMV had a sequence clearly different from other viroids, including citrus exocortis viroid, apple scar skin viroid (ASSV), hop stunt viroid (HSV) and avocado sunblotch viroid. The possible significance of the limited sequence homology shared by PLMV with HSV, and especially with ASSV, is discussed. PMID- 2326552 TI - Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells. AB - Tetracycline analogs were evaluated for anti-HIV activity in CEM cells; minocycline and doxycycline were the most active of these in inhibiting the virus induced cytopathic effect between 7 and 14 days post-infection. The active concentrations (0.3-1.5 micrograms/ml) were devoid of toxicity in uninfected cultures. Virus production, however, was not inhibited, indicating a dissociation between protection against cell death and suppression of virus growth. These protected cells could be maintained in culture for 6-7 weeks, even in the absence of the compounds. After that period, virus production ceased and cells could then be cultivated for several months without loss of viability or reappearance of virus production. As HIV stocks produced in the presence of tetracycline analogs were unable to induce cell death, we suggest that the cytopathogenicity of HIV may be due in some cases to the presence of tetracycline-sensitive contaminating microorganisms. PMID- 2326553 TI - Identification of a 334-ribonucleotide viral satellite as principal aetiological agent in a tomato necrosis epidemic. AB - Cucumber mosaic virus (CMV), a widespread and economically important virus of vegetable crops, often contains a satellite RNA, here designated CARNA-5 (for CMV associated RNA 5). Viral satellites are small nucleic acids that are sequence unrelated to, but replicatively dependent upon, the viral genome. They essentially are molecular parasites of their helper viruses, and thereby frequently modulate viral symptom expression. Some isolates of CARNA-5 change normally moderate CMV symptoms in tomato into a lethal disease named tomato necrosis; others ameliorate CMV symptoms in tomato and other important crop plants. Here we report on the identification and molecular characterization of a 334-nucleotide necrogenic CARNA-5 isolated from tomato fields in southern Italy, where a massive outbreak of lethal necrosis occurred in the summer of 1988. This is the first time that direct evidence is given for the involvement of a viral satellite in a crop disease of epidemic scale. The possible molecular interrelationships between plant, virus, satellite and other factors that influence the satellite-induced symptom modulation underlying such a catastrophe are discussed. PMID- 2326554 TI - [Peliosis hepatis in dermatomyositis treated with azathioprine and corticoids]. AB - We report a case of peliosis hepatis in a 47-year old male patient with dermatomyositis treated with azathioprine and corticosteroids. Three months after the combined treatment was initiated, the patient developed right thoracic herpes zoster, agranulocytosis and liver enlargement with signs of portal hypertension. Needle biopsy of the liver revealed peliosis. Azathioprine was withdrawn. The clinical and laboratory abnormalities disappeared progressively. The main causes of peliosis hepatis are considered. Up to now, azathioprine had been held responsible for peliosis hepatis only in renal transplant recipients. PMID- 2326555 TI - [Cerebral arterial ischemic complications in young adults. Etiology and prognosis]. AB - The authors investigated 100 patients (55 males and 45 females) aged 16 to 45 years who experienced cerebral ischemic attack, excluding venous thrombosis. Transient ischemic attacks accounted for 12% only. Attacks were related to usual causes of brain ischemia in 49 cases (premature atherosclerosis in 26, cardiopathy in 20 and lacunar stroke in 3). Thirty-eight events were attributed to most uncommon etiologies. Nonatherosclerotic arteriopathies (10 cases) such as spontaneous dissection, dysplasia or megadolichoarteries were easily diagnosed by angiography. Oral contraceptives (14 cases) and migraine (2 cases) were diagnosis of exclusion. Hematological disorders were a possible cause in 10 patients. Etiology remained undetermined in 13 cases. Four patients died acutely. Follow-up data were obtained in 93 survivors with a mean duration of 26 months (range, 6 to 60 months). Four subjects died during follow-up and 6 experienced recurrent stroke (annual recurrence rate: 3%). In activities of daily living, 64% of patients had complete autonomy while 13% had mild residual disability and 23% had severe handicap. PMID- 2326556 TI - [Diagnostic significance of low thyrotropin in internal medicine]. AB - In an attempt to determine the significance of low plasma thyrotropin (TSH) concentrations in internal medicine and the usefulness of systematic TSH assays in hospitals, 732 consecutive TSH measurements were performed in first-admission patients. TSH concentrations below 0.15 mU/l were found in 33 patients (4.5%) divided into 4 groups: a) in 5 patients a second assay made within 10 days of the first one showed no fall in TSH levels; b) 5 patients had known endocrine disease; c) in 8 patients hyperthyroidism could be asserted; the diagnosis had not been suspected in 3 elderly women and 1 pregnant women; d) 15 patients remained with low TSH concentrations but had normal free T3 and free T4 levels; in this group a goitre was detected in 7 patients and 8 had a severe chronic disease. These results showed that a TSH concentration below 0.15 mU/l corresponded to hyperthyroidism in less than one out of three patients in this population and that the 0.07 to 0.15 mU/l range is particularly misleading. A second TSH assay, free T3 and free T4 measurements ant thorough investigations in search of a goitre must be made. Severe organic diseases and several drugs may induce a fall in TSH. All considered, the 1% prevalence of hyperthyroidism in this population does not justify systematic TSH assays, but in subjects over 60 years of age, the clinical manifestations of hyperthyroidism may be misleading or unrecognized, and TSH assays should be widely performed. PMID- 2326557 TI - [Buccal lymphomatoid granulomatosis]. AB - A 57 year old man was referred to us with multiple long-standing, recurring and refractory mouth ulcers involving the palate, the intermaxillary folds, the inner side of the cheeks, the frenum of the tongue, a tonsil, the pharynx, the gums and a lower lip. Multiple biopsies had excluded a lymphoma, a carcinoma and infection. A new biopsy showed a polymorphous granuloma with up to 40% of atypical lymphoid cells. No angiitis was present, but an angiocentric pattern was present in the granuloma. The atypical cells stained positively with OKT3 and OKT4 antisera. The patient also had cardiac rhythm disturbances with defects on the myocardial scan and a proteinuria. Thus, we suspected the diagnosis of lymphomatoid granulomatosis, although there were no pulmonary nodules. Cyclophosphamide and prednisone were given with immediate success. As the doses were gradually decreased, a small relapse occurred. It was controlled by increasing the cyclophosphamide dosage for six months. The patient is now in complete remission more than four years after having discontinued the treatment. Thus, lymphomatoid granulomatosis can be diagnosed on the basis of a biopsy of buccal ulcers and in the absence of the classical pulmonary nodules. We found no evidence that the atypical cells were lymphomatous; rather, the very good response to the treatment points to a curable granulomatosis. PMID- 2326558 TI - [Erythema multiforme, aplasia, cholestatic hepatitis during treatment with Augmentin (amoxicillin + clavulanic acid)]. PMID- 2326559 TI - [Hepatic sarcoidosis simulating primary biliary cirrhosis: a new case]. PMID- 2326560 TI - [X-ray computed tomographic aspects of mediastinal fibrosis. Apropos of a case]. PMID- 2326561 TI - [Chronic lactic acidosis and acute lymphoblastic leukemia]. PMID- 2326562 TI - [Perihepatitis and C2 deficiency. Relation to lupic disease?]. PMID- 2326563 TI - [Persistent hyperparathyroidism caused by adenoma in supernumerary retroesophageal parathyroid: value of radionuclide location]. PMID- 2326564 TI - [Solitary plasmacytoma of the thyroid]. PMID- 2326565 TI - [Association of celiac disease with Hodgkin's disease of a digestive site]. PMID- 2326566 TI - Learned self-help response to chronic illness experience: a test of three alternative learning theories. AB - The purpose of this study was to generate a self-help model depicting the essential dynamics of learned response to chronic illness experience. The method used to generate a self-help model was based on theoretical triangulation, as discussed by Houts, Cook, and Shadish (1986), Mitchell (1986), and Reichardt and Cook (1979). Theoretical triangulation, incorporating multiple perspectives and hypotheses in the same study, is a form of critical multiplism leading to testing of multiple rival hypotheses rather than single ones (Popper, 1972; Stinchcombe, 1968) and to construction of complex multivariate causal models instead of simple univariate ones (Blalock, 1961). Strong relationships were found between enabling skill, self-help, and life quality. PMID- 2326567 TI - Responsible subversion: a study of rule-bending among nurses. AB - The purpose of this qualitative field research was to explore and describe how nurses bend the rules for the sake of the patient. Responsible subversion is the construct that describes such behaviors. The research purpose and initial data were derived from participant-observation and interview data from a study of unprofessional behavior in hospital-based nurses. In-depth interviews with 21 nurses from four clinical areas provided additional data. The grounded theory method was used for data analysis. Data analysis revealed that given certain conditions--knowledge,ideology,experience--nurses engaged in responsible subversion. Responsible subversion involves four phases: (1) evaluating, (2) predicting, (3) rule-bending, and (4) covering. This conceptualization raises important issues in the area of ethics and the socialization of nurses. PMID- 2326568 TI - The relationship of attitude, subjective norm, and behavioral intent to the documentation behavior of nurses. AB - Ajzen and Fishbein's theory of reasoned action was used to assess the relationship of nurses' attitude, subjective norm, and behavioral intention to their documentation behavior. Attitudes, subjective norms, and behavioral intentions toward documentation were elicited from 108 staff nurses. Documentation behavior was based on what should be documented in any hospitalized patient's chart during a shift. This exploratory model was analyzed with LISREL VI. The overall fit of the final model to the data was good, as judged by a chi square (df = 7, p = .845). The total coefficient of determination for the structural equation was .461. Attitude toward documentation did not relate significantly to intention to document optimally. Subjective norm did have a significant effect on behavioral intent. Attitude and subjective norm accounted for 46.1% of the variance in behavioral intent. Behavioral intent had a significant effect on documentation behavior, accounting for 15.2% of the variance. It appears that subjective norm, which is the influence of others, is what directs the intention to document and thus relates to subsequent documentation. Recommendations for practice include the communication of high ideals and expectations of important others to the staff nurse in order to improve the quality of documentation. PMID- 2326569 TI - Violent psychiatric inpatients in a public hospital. AB - Violence in inpatient psychiatric settings is a clinically significant and relevant problem requiring attention by the psychiatric community. Despite the prevalence of research on violent behavior, few nursing studies have been conducted that explore the components of nursing care that may influence the amount of violence occurring in inpatient psychiatric settings. The purpose of the study was to identify the characteristics of violent patients and the components of nursing care that are related to violent patient behavior. A qualitative study was conducted using participant observation and grounded theory methodology. Data were collected in a metropolitan public hospital over a 9-month period. Six categories of violent patients were identified during data analysis: (1) the user, (b) the outlaw, (c) the rebel without a cause, (d) the little big man, (e) the child, and (6) the vamp. Implications of the study for clinicians working in inpatient psychiatric settings are discussed. PMID- 2326570 TI - [General nutrition of pregnant women]. AB - The ideal weight gain during pregnancy is approximately 9 to 12 kilos. The energetic intake should not be very high (+250 kcal at term). The protein consumption during pregnancy is low during the first trimester. A 10 to 20 g daily increase in the diet, from the 3rd month, suffices to cover the requirements and provide the supplemental calories necessary to the intake. Meat should be left in the diet, at least two or three times per week as it supplies iron and vitamin B12; fish should also be preferred because of its low content in rich fats and polyunsaturated fatty acids. Bread and starches are often wrongly rejected. Sweets taken between meals are most of the time responsible for excessive weight gain because of their high hyperinsulinemic properties. Animal lipids are digested slowly and with difficulty. Their consumption should be restricted and vegetal oils rich in polyunsaturated fats used instead. Fruit and vegetables must provide abundant amounts of vegetal fibers, minerals and vitamins. Sufficient water intake and proper feeding rhythms are absolutely necessary to a good progression and comfort of the pregnancy. PMID- 2326571 TI - [Nutrition and oligo-elements during the course of pregnancy. Conference organized by the French Society for Study and Research on Essential Trace Elements]. PMID- 2326572 TI - [Maternal oligo-elements and fetal malformations]. AB - Serum levels of zinc, copper, manganese, magnesium, folates and vitamin B12 and A, were titrated in the early stage of pregnancy in women who delivered children presenting malformations. These levels were compared with those of control patients who delivered normal children. There were 65 malformations. The most frequent were cardiac, musculo-skeletal, urogenital and chromosomal malformations. Only 2 cases of spina bifida were studied. The oligo-elements and vitamin levels are not different in both groups of women: those who carry malformed fetuses and those carrying normal fetuses. These results are compared with those from the literature. PMID- 2326573 TI - [Treatment of cancer of the breast]. PMID- 2326574 TI - [Epidemiologic and prognostic factors of cancer of the breast]. AB - Breast cancer is the most common of all cancers affecting women in France; its frequency increases in countries with a high standard of living. A family history and certain types of mastosis are unquestionable risk factors, although their weight has not yet been well established, but there is no absolute proof that feeding habits (notably fats and alcohol), which have been blamed by some authors, play a role in the genesis of breast cancer. Among the classical prognostic factors, which are necessary for surgical decisions, the size of the tumour, its histological grade and above all the number of axillary lymph nodes involved are the most important. However, a better knowledge of breast cancer biology has yielded factors that seem to be more promising than hormonal receptors, notably the DNA content of tumoral cells and the presence or absence of a protease, procathepsin 52 K, which reflects tumoral aggressiveness. As for the study of oncogens described elsewhere in this monograph, it will provide a better definition of high risk subjects and more precise information on the progress of the cancer. PMID- 2326575 TI - [Treatment of tumors of the breast less than 3 cm in diameter]. AB - In many cases of breast cancer mammectomy can be an excessive treatment. Conservative treatments, such as radical radiotherapy alone or combined with tumorectomy, have proved oncologically effective. All retrospective studies and several prospective randomized studies have yielded local control and survival values that were not significantly different in patients treated by maiming radical surgery and in patients treated with conservative techniques, with satisfactory cosmetic and functional results. A critical study of reasons for failure of conservative treatments, taking into account mostly the size and multicentric character of the tumour, shows that, with the exception of tumours developed in small breasts or in particular sites suggesting a high risk of extension to the skin, the chest wall or the lymph nodes, tumours less than 3 cm wide are a good indication of conservative treatment. PMID- 2326576 TI - [Can tumors of the breast larger than 3 centimeters be treated conservatively?]. AB - Unlike small breast cancers, which are now treated conservatively by primary tumorectomy, the most important lesions (T2 and T3) as usually treated tumorectomy, the most important lesions (T2 and T3) as usually treated by mastectomy. However, in patients with these large lesions attempts may be made at conserving the breast with reliable oncological safety and good cosmetic results. Depending on clinical presentation, one or the other of two therapeutic approaches may be considered. The most common treatment is preoperative radiotherapy of 45 Gy which, in more than 50 p. 100 of the cases results in a tumoral regression that is sufficient for secondary tumorectomy to be performed. In some patients, the first-line treatment consists of wide tumoral excision as part of a reductive mammaplasty, followed by radiation. PMID- 2326577 TI - [Inflammatory cancer]. AB - Inflammatory carcinoma of the breast accounts for 1 to 4 p. 100 of breast cancers. It is a very serious form universally considered as a primarily systemic disease. The initial treatment is always systemic; primary surgery is contra indicated. Most chemotherapeutic protocols result in objective response in 50 to 80 p. 100 of the cases. Depending on the response, local treatment consists of radiotherapy alone or combined with surgery. In spite of recent advances, the 5 year survival rate still ranges from 30 to 48 p. 100. Better prospects are in sight, however, owing to the study of prognostic factors, notably in the fields of oncogens and resistance to chemotherapy (MDR gene). Massive chemotherapy with autologous bone marrow transplantation or the use of haematopoietic growth factor will certainly play a part in treatment, but their value remains to be determined. PMID- 2326578 TI - [Gene amplification and virologic diagnosis]. PMID- 2326579 TI - [Summary of the proceedings of the consensus on emergency treatment of upper digestive hemorrhage in portal hypertension of cirrhosis, Paris, 17 November 1989]. PMID- 2326580 TI - [From absence of consent to violation of personal rights]. PMID- 2326581 TI - [Ascites. Diagnostic orientation and management]. PMID- 2326582 TI - [Growth and weight gain. Elements of estimation]. PMID- 2326583 TI - [Growth retardation. Etiology, diagnosis, evolution and prognosis]. PMID- 2326584 TI - [Scapulohumeral periarthritis. Etiology, physiopathology, diagnosis and principles of treatment]. PMID- 2326585 TI - [Cancer of the stomach. Diagnosis, complications, principles of surgical treatment]. PMID- 2326586 TI - [Immune deficits in hemodialysis patients]. AB - Patients with chronic renal insufficiency under maintenance dialysis present numerous immunological alterations to which renal impairment, nutritional disturbances, blood transfusions and biocompatibility of the dialysis system may contribute. Although presently less frequent, infections still represent an important source of mortality and morbidity. Polynuclear neutrophils chemotactic responses are decreased and bactericidal capacity reduced, especially in polytransfused patients with iron overload. Lymphocyte counts are diminished and T lymphocytes present several alterations, including defective IL-2 synthesis, spontaneous expression of the p55 (CD25) chain of IL-2 receptor with high serum levels of this molecule, and defective T helper function in antibody production. Such alterations may account for the defect of delayed hypersensitivity reactions and the diminished antibody response after vaccination. Complement activation, increased expression of adhesion molecules by leukocytes, production of IL-1 and reduced oxygen molecular species during dialysis might contribute to immunological disorders of these patients. PMID- 2326587 TI - [Renal osteodystrophy: aluminium and secondary hyperparathyroidism]. AB - Aluminium-related osteodystrophy results in osteomalacia or in the so-called aplastic bone. In this particular bone disease bone cells activities are distinctly reduced but there is no disorder of bone mineralization. Aluminium exerts a direct toxic effect on bone tissue, notably on osteoblasts which are always strongly depressed in case of major aluminium overload. Aluminium-related osteopathy is regularly accompanied by low levels of parathormone due to accumulation of aluminium in the parathyroid glands. Parathormone modulates the bone aluminium overload: hyperparathyroidism "protects" bones against the deleterious effect of aluminium, whereas aluminium deposit in bone increase after parathyroidectomy. The respective roles played by low parathormone levels and by aluminium deposits in aplastic bone lesions is difficult to determine since hypoparathyroidism itself can probably cause the aplastic osteopathy. The role of parathormone stands out more clearly now that in patients under dialysis the bone aluminium overload has markedly decreased. Many patients with aplastic bone (initially described in aluminium poisoning) show no aluminium deposits in bones but have, for some unknown reason, a normal or even low parathormone level. The clinical course of this type of osteopathy remains to be determined, but there seems to be no reason to worry since numerous patient are asymptomatic. Preventing secondary hyperparathyroidism while refraining from prescribing aluminium hydroxide is the principal therapeutic objective in osteodystrophy of haemodialysis patients. PMID- 2326588 TI - [Cardiovascular repercussions of chronic hemodialysis]. AB - Coronary disease and left ventricular failure are the two main causes of death in haemodialysis patients. In these particular patients it is the accumulation of several risk factors rather than accelerated atherogenesis which seems to be the responsible for the frequent manifestations of a coronary disease which is sometimes difficult to diagnose. Independently of any cardiovascular history, the so-called "uraemic cardiopathy" is characterized by left ventricular dilatation associated with an increased myocardial mass but with a low mass/volume ratio. The systolic function is preserved whereas the ventricular diastolic compliance is altered due to the left ventricular hypertrophy. PMID- 2326589 TI - [Psychiatric disorders in patient with chronic kidney failure]. AB - The psychiatric complications and adaptation disorders observed in patients with chronic renal failure under maintenance haemodialysis are reviewed. The main psychiatric complications are depressive manifestations, while the main adaptation disorders are lack of compliance with food and water restrictions and temperamental relations with the husband or wife or the dialysis team. The mechanisms of some disorders are analyzed, and emphasis is placed on the usefulness of psychiatric and/or psychological assistance not only to the patient but also to his wife and to the medical staff. PMID- 2326590 TI - [Neurologic complications in hemodialysis patients]. AB - Various neurological complications may occur in patients under haemodialysis for end-stage chronic renal failure. Their frequency has clearly been reduced by improvements in the modalities and techniques of dialysis. Some of these complications are related to uremia and/or to the accumulation of endogenous toxic substances the nature of which has not been elucidated (e.g. uraemic encephalopathy, polyneuropathy), while others are directly due to the haemodialysis itself (e.g. dialysis disequilibrium syndrome, aluminum encephalopathy). PMID- 2326591 TI - [Current therapeutic use of somatostatin analogs]. PMID- 2326592 TI - [The World Congress of Radiology. Paris, 1-8 July 1989]. PMID- 2326593 TI - [Epistaxis, airway hemorrhage in adults. Etiology, diagnosis, principles of treatment]. PMID- 2326594 TI - [Non-Hodgkin's lymphoma. Diagnosis, principles of treatment]. PMID- 2326595 TI - [Abdominal contusion. Pathologic anatomy, diagnosis, development and prognosis, principles of surgical treatment]. PMID- 2326597 TI - [Herpes hominis infections. Epidemiology, physiopathology, diagnosis, development and prognosis, treatment (mode of action of drugs]. PMID- 2326596 TI - [Headache, facial neuralgia. Diagnostic orientation and management]. PMID- 2326598 TI - [Taenia saginata. Epidemiology, diagnosis, treatment]. PMID- 2326599 TI - Antibacterial activity of dental gels containing combinations of amine fluoride, stannous fluoride, and chlorhexidine against cariogenic bacteria. AB - The in vitro susceptibility of Streptococcus mutans, S. sobrinus and Lactobacillus casei to dental gels containing various combinations of amine fluoride (AmF 297), stannous fluoride (SnF2), and chlorhexidine (CHX) was studied. The combination of AmF-SnF2 with a total fluoride content of 1.2% was the most effective against mutans streptococci but not against L. casei. At notably lower total fluoride concentration (0.4%), AmF as such or combined with SnF2, was significantly less effective against mutans streptococci than CHX or CHX-AmF-SnF2 combinations. CHX-AmF combination was a slightly more potent inhibitor of streptococcal growth than CHX-NaF. With L. casei the differences between various gels were small but CHX alone seemed to be the most effective. Of the studied agents, CHX seemed to be the most potent individual chemotherapeutic compound whose activity against S. mutans could be enhanced by combining it with AmF. However, clinical experiments are required to test the in vivo antibacterial efficacy of CHX-AmF and AmF-SnF2 combinations which were most effective in our in vitro experiments. PMID- 2326600 TI - Mandibular condyle lesions, jaw movements, and occlusal status in 15-year-old children with juvenile rheumatoid arthritis. AB - The purpose was to determine the number and severity of lesions in the temporomandibular area and their association with occlusal status and mandibular movements in 15-yr-old children afflicted with juvenile rheumatoid arthritis (JRA). The series comprised 121 JRA children, 78 girls and 43 boys, and a control group of 104 schoolchildren, 70 girls and 34 boys, taken for clinical examination. Of the JRA children, 55% had roentgenologically detectable lesions in the TMJ area. Lesions were found in 60% of the girls and in 42% of the boys, the ratio thus being 3:2. The largest group had grave lesions (48%), the second largest displayed flattening of the condyle (43%) and the smallest a flattened condyle with a minor lesion (9%). There were more bilateral lesions in the children with the severest lesions. Tendencies for Class II malocclusion, small vertical overbite and open bite were visible in the JRA children. Reduced maximal opening capacity, maximal protrusion, lateral movements of the mandible and pain in the TMJ area proved to be reliable signs predicting temporomandibular joint involvement in JRA children. Maximal mouth opening capacity was significantly restricted in the patients showing condylar lesions as compared with patients having no lesions or with controls. JRA children should be divided according to sex and the severity of the lesions. The JRA children without TMJ lesions had normal values for mandibular movements and were thus comparable to healthy children. PMID- 2326601 TI - Oral radiographic screening in Danish children. AB - The aim of the present study was to ascertain frequency and type of radiographic screening in the Danish Dental Service for children. A 5-item questionnaire was sent to each department of public dentistry in the 275 communities of Denmark. A total of 269 questionnaires were returned, four unanswered. Radiographic screening examinations were done on 162 respondents. Of these, 25% had bitewing screening and 25% panoramic screening. Two types of routine radiographic examinations were performed on more than one third of the respondents. The most frequent combination for screening radiography was bitewing and panorama. Even though the risks included in the use of ionizing radiation for dental screening purposes may be considered negligible, it is still ethically correct to avoid unnecessary exposure by a careful selection of patients prior to radiography. As economic support for dental health care had been cut, the radiographic screening procedure must prove itself to be cost/effective to be kept unchanged. PMID- 2326602 TI - The functional recovery of stroke: a comparison between neuro-developmental treatment and the Brunnstrom method. AB - The relative efficacy of Neuro-Developmental Treatment (N.D.T.) versus the Brunnstrom method was studied from the perspective of the functional recovery of stroke patients. An alternating treatment design (B-C-B-C) was used. Each intervention phase lasted 5 weeks. The functional recovery of the patients was assessed every week by using the Barthel Index and the Action Research Arm test, by registering walking velocity, and by performing gait analysis. At the start and at the end of each intervention phase, neurological and neuropsychological assessments took place. Time series analysis indicated that for one patient only, walking speed progressed more during the Brunnstrom phases than the N.D.T. phases. This result did not generalize towards other parameters or patients studied. For upper extremity function and maximum walking speed, a high correlation was found between the week post stroke in which the patient showed the first signs of recovery and the end condition after 20 weeks. PMID- 2326603 TI - Can high-risk patients after myocardial infarction participate in comprehensive cardiac rehabilitation? AB - Patients with large transmural infarctions (MI) and signs of congestive heart failure (CHF) are often excluded from physical training, because of the risk of malignant arrhythmia or cardiac overloading. From a non-selected MI population less than 65 years we enrolled 37 high-risk patients in a two-year comprehensive cardiac rehabilitation programme, including health education, follow-up at a post MI clinic, and physical training in outpatient groups. The feasibility, effectiveness and safety of the physical training were evaluated: Twenty-one patients joined the physical training and participated with excellent compliance, reaching the preset levels of training. No adverse effects occurred during the 921 training sessions. The high-risk patients were compared with the remaining 228 patients and a subgroup of 86 low-risk patients with regard to mortality, morbidity, medication, effect on risk factors, exercise test performance and rate of return to work. The high-risk group showed a higher mortality (27.0 vs. 10.4%, p less than 0.05), a lower maximal work capacity at the exercise test 4 months after MI (126 W vs. 140 W, p less than 0.05), and a lower rate of early return to work (22.6 vs. 50% p less than 0.01) when compare with the low risk group. However, they showed a similar improvement in exercise test parameters. At the end of the programme a remarkable 63% had returned to work vs. 48.2% of the remaining patients. The reduction in smoking and the effect on blood pressure were equal in both groups. It is concluded that high-risk patients may well benefit from regular physical training in outpatient groups, if adequate medical supervision is available. PMID- 2326604 TI - Increased spinal mobility in adolescents with bronchial asthma. AB - Spinal mobility was measured in thirty-five adolescents (21 boys and 14 girls) with bronchial asthma. Comparisons were carried out with an equal number of healthy controls matched for sex, age, weight, and height. Thoracic spinal movements of rotation and lateral flexion in girls and of rotation in boys were significantly greater in asthmatics as were the sagittal lumbar movements with the exception of forward flexion in the boys. Sagittal spinal curvatures of the asthmatics did not significantly differ from those of the controls. The results indicate that there are no need of explicit mobilization of thoracic spine in asthmatic children. PMID- 2326605 TI - Experimentally induced ischemic pain and so-called diaphase fix current. AB - It has been claimed that the diadynamic currents have either analgesic or other beneficial effects during the treatment of various painful musculoskeletal disorders. However, no experimental or controlled clinical results have been presented to support these claims. In this study, the possible analgesic effect of the DF (diaphase fix)-current on experimental pain was evaluated. An ischemia was experimentally induced in the left arm of five healthy male volunteers by a modified submaximal effort tourniquet test. Each subject had two consecutive ten minute periods of ischemia, one with and another without the DF-current. The subjective pain responses to the ischemia were measured by the visual analogue scale. The DF-current did not cause any marked decrease in the mean pain responses in this experiment. This experiment did not support the idea of using the diadynamic currents in alleviating musculoskeletal pain. PMID- 2326606 TI - Effect of forced running on rat skeletal muscle with acrylamide neuropathy. AB - This study was performed to evaluate the effect of prolonged forced running on rat lower limb muscles with acrylamide neuropathy. Twenty-four 4-week-old rats were divided into three groups of eight rats. Acrylamide was given to two groups of sixteen rats to induce mild paralysis. Eight rats with acrylamide injections were forced to run 3,200 m/day on a treadmill for five weeks. Running activities slowed the rate of body weight gain and aggravated paralysis. Although the wet weight of tibialis anterior (TA) and extensor digitorum longus (EDL) muscles was reduced by running, that of soleus (SOL) muscles was unchanged. The ratio of their weight to their body weight (BW) remained constant regardless of exercise. Protein content (PC) of muscles was not altered by exercise, either. We postulated that exercise-induced worsening of paralysis in acrylamide neuropathy rats was not caused by muscle pathology. Deterioration of neuropathic condition due to exercise was suggested. PMID- 2326607 TI - Long-lasting unilateral muscle wasting and weakness following injury and immobilisation. AB - Quadriceps strength and size was measured in a small group of subjects (n = 7) 1 to 5 years after full mobilisation following some form of unilateral lower limb trauma. The mean maximum voluntary isometric force (MVC) was significantly lower for the injured (I) compared to the uninjured (UI) leg (369 N +/- 139 vs. 535 N +/- 131, p less than 0.01). Electrical stimulation superimposed on the voluntary contractions demonstrated that all subjects were able to maximally activate the quadriceps of both legs. Mean quadriceps cross-sectional area (CSA) was significantly lower in the I (64 cm2 +/- 12.8) compared to the UI leg (80 +/- 12.8, p less than 0.01). One subject with marked unilateral weakness and wasting took part in a 3-month strength training study for the injured leg. After training the I/UI ratio had been restored to nearly 100% (94% MVC; 88% CSA). These results would suggest that longer and more intensive physiotherapy is required in the immediate post-injury period to restore muscle strength and size to severely atrophied muscle. PMID- 2326608 TI - Isokinetic strength training in below-knee amputees. AB - Eight below-knee amputees performed isokinetic training of knee extensor- and knee-flexor muscles for a period of 8-12 weeks at angular velocities of 60 degrees/s, 180 degrees/s and 240 degrees/s. Before and after training isokinetic and isometric knee extensor/flexor strength was measured. Muscle biopsies were taken from the vastus lateralis and the cross-sectional area of the thigh muscles was measured with computerized tomography. Peak torque of the amputated leg increased significantly in all knee-extension tests and in knee-flexion at 180 degrees/s, and in the non-amputated leg in extension at 180 degrees/s, 240 degrees/s and for isometric strength at 60 degrees knee angle. Knee-flexion strength increased at 240 degrees/s. The cross-sectional area of the muscle fibers increased in the amputated leg in all patients except one. There was no significant increase in the non-amputated leg which also was trained. The quotient between the cross-sectional areas of type II and type I fibers increased from 1.04 to 1.20 in the amputated leg, demonstrating an increase specially in the type II fibers. There was no difference in the non-amputated leg. The cross sectional area of the thigh muscles did not show any significant change in either leg. The patients estimated their ability to walk after training to more than double the distance compared to before training. They could also manage better without walking aids. The increase in strength and the synchronous increase in the size of type II (fast twitch) fibers indicate that the training model has activated also these motor units which probably have not been given as much training earlier. PMID- 2326609 TI - Assessment of walking before and after unicompartmental knee arthroplasty. A comparison of different methods. AB - Walking ability was assessed in twenty patients before and one year after knee replacement with a cemented unicompartmental, Brigham prosthesis (mean age 63.4 years, nine women). All patients had moderate medial gonarthrosis. One year after surgery, knee function, assessed by the BOA score, self-selected and maximal walking speed as well as single limb support of the involved leg were increased. Pain and exertion during walking and oxygen cost of level walking were decreased at all measured speeds. Individual improvement in self-selected walking speed was correlated to improvement in maximal walking speed. Individual decrease of oxygen cost of level walking was correlated to decrease of perceived pain and exertion during walking. For clinical routine purpose clinical assessment, especially of pain, supplemented with measurement of self-selected walking speed were found to be sufficient for assessing effects of treatment such as unicompartmental prosthetic knee replacement. PMID- 2326610 TI - The increase in energy cost of walking with an immobilized knee or an unstable ankle. AB - The effect of an immobilized knee joint or of an unstable ankle joint on the walking capacity has been assessed with 50 walking tests in ten healthy subjects. The knee joint was immobilized in extension with a standard splint and an unstable ankle joint was simulated by a modified shoe. A significant decrease in convenient walking speed was found. The energy cost of walking as assessed by oxygen cost at a convenient speed was significantly increased both with an immobilized knee (23%) and with an unstable ankle (10%), compared to normal condition of the subjects. Implications for the management of patients with similar joint disorders are discussed. PMID- 2326611 TI - Walking efficiency before and after long-term muscle stretch in patients with spastic paraparesis. AB - Eight patients with stationary, spastic paraparesis were treated with long-term stretch of the hip adductor muscles to improve walking ability. Gait pattern, walking speed and perceived exertion of walking were assessed. Walking efficiency was assessed before and after treatment by measuring oxygen consumption and blood lactate level. After treatment walking pattern was improved. Perceived exertion decreased but walking speed was unchanged. Oxygen cost directly after treatment was lower in six patients, unchanged in one and higher in one. In the patient with unchanged oxygen cost the blood lactate level decreased, probably due to decreased recruitment of fast, type II muscle fibres. Blood lactate was unchanged in the other patients. When assessing walking ability, measurement of energy cost was found to be a valuable supplement to clinical judgement, but in spastic patients both oxygen cost and blood lactate must be considered. PMID- 2326612 TI - Testing daily functions post-stroke with standardized practical equipment. AB - Two hundred and seven stroke patients were tested with Standardized Practical Equipment (SPE) three months after a stroke. One year after the stroke 183 survivors from this stroke population were tested with the equipment. The SPE test consists of 12 common daily activities, which the patient was asked to perform. The construct validity of SPE was estimated by factor analysis from the results of one-year follow-up. Three factors explained 82% of the variance of the 12 variables of SPE. Factor 1 mainly concerned cognitive factors and co ordination, Factor 2 construction and hand function and Factor 3 variables that were dependent on mobility and balance. No significant difference was noted between the performance with SPE three months and one year after the stroke among the one-year survivors. There were some differences between men and women; for example the men were more successful in tasks with technical components. The women had more difficulty with some of the tasks involving mobility, such as climbing stairs without support. The Standardized Practical Equipment gave good additive information about the ability of a stroke patient to manage at home and could be used in any set-up. PMID- 2326613 TI - [Sepsis caused by Fusobacterium necrophorum: the re-discovered postangina sepsis Lemierre syndrome and other manifestations]. AB - Among 5 patients with bacteremia due to Fusobacterium necrophorum, 3 young adults had post-anginal sepsis (Lemierre syndrome), including one with the classical secondary metastatic complications of pulmonary abscesses, pleural empyema, arthritis and hepatobiliary disturbances. The primary focus was a cholangiogenic abscess in an 81-year-old woman, and fetid otitis following a radical operation for cholesteomatous chronic otitis media in a 29-year-old male. Septicemia due to Fusobacterium necrophorum, and in particular Lemierre syndrome, are presented in the light of the literature. PMID- 2326614 TI - [Baking ingredients, especially alpha-amylase, as occupational inhalation allergens in the baking industry]. AB - Baker's asthma is the most frequent occupational lung disease in Switzerland and West Germany. Cereal flours, and more rarely flour parasites, are implicated as the responsible allergens. Based on an observation of a case of baker's asthma due to monovalent sensitization to alpha-amylase used as additive to flour, 31 bakers with occupational asthma and/or rhinitis were routinely tested by skin tests and serological RAST examinations for allergic sensitivity to flour, alpha amylase and other bakery additives. 17/31 subjects (55%) reacted positively in scratch tests to a commercial powdered alpha-amylase and 13/20 (65%) to a lecithin preparation. 23/31 (74%) and 19/31 (61%) were RAST positive to wheat and to rye flour respectively. 32% had RAST specific IgE to alpha-amylase (from Aspergillus oryzae), 19.3% to soya bean flour and 16% to malt. 7/12 and 5/12 respectively reacted to trypsin inhibitor and lipoxidase, the main allergens in soya bean. In two patients monosensitization to alpha-amylase was present. In accordance with other reports we recommend that baking additives, especially alpha-amylase, should be tested in allergological diagnosis of occupational diseases in flour processing workers. Full declaration of all additives used in the bakery industry is needed. PMID- 2326616 TI - Utilization of masks by Hutterite farmers. AB - Respiratory symptomatology and pulmonary function tests were evaluated among 199 male Hutterites who utilized masks during farming and 159 Hutterites who did not use masks. Anthropometric and pulmonary function tests were comparable between the two groups. Symptomatology, including cough, phlegm, and wheezing were more prevalent among mask wearers compared to non-mask wearers. The prevalence of hayfever (p less than 0.02) and asthma (p less than 0.001) was greater among mask wearers vs non-mask wearers. Although the types and percent of individuals from each group raising crops and livestock were comparable, breathlessness, wheeze and fever were more common among the mask wearers. Thus farmers who suffered a higher incidence of symptoms as a consequence of farming are more likely to use masks. PMID- 2326615 TI - [Sustained ventricular tachycardia: inducibility during invasive electrophysiologic studies]. AB - Electrophysiologic studies are used for diagnosis and treatment in patients with sustained ventricular tachycardia. This method can only be employed if high inducibility of the spontaneous tachycardia can be demonstrated. We therefore investigated prospectively the induction yield in 35 patients with a history of documented sustained ventricular tachycardia. The patients' mean age was 58 years. Coronary artery disease was present in 24 patients, cardiomyopathy in 4, other organic heart diseases in 4, and no heart disease in 3. The ventricular tachycardia induction protocol consisted of three extrastimuli delivered during sinus rhythm and at two pacing cycle lengths, followed by intravenous isoproterenol if no tachycardia was induced before. With the method sustained ventricular tachycardia was induced in 100% of patients with coronary artery disease and cardiomyopathy, in 75% of patients with other heart diseases and in 33% of patients without detectable heart disease. We conclude that electrophysiologic studies have a high yield of sustained ventricular tachycardia induction in patients with underlying organic heart disease. The rational basis for use of electropharmacologic testing therefore exists in these patients. However, in patients without heart disease, the low sensitivity of electrophysiologic studies precludes its use for drug efficacy testing. PMID- 2326617 TI - Quality, cost, liability. PMID- 2326618 TI - Distribution of heavy metals in Gove Harbour, Northern Territory, Australia. AB - The concentration of four metals in waters and eight metals in oysters and sediments from Gove Harbour, Northern Territory, were determined during the dry season of 1987. The measured concentrations of zinc, cadmium, copper and lead in unfiltered waters were: 1.10-7.28, 0.10-2.20, 0.25-3.45 and 0.15-2.87 micrograms l-1, and zinc, cadmium, copper, lead, aluminium, nickel, manganese and iron in oysters, 60.1-970, 0.14-4.07, 3.77-30.67, ND-0.46, 6.50-1123.0, 0.02-0.44, 0.24 2.04 and 4.28-981.3 micrograms g-1 wet weight, and in sediments, 0.09-22.24, ND 0.45, ND-5.95, ND-2.98, 229.98-16053.5, 0.21-7.70, 13.77-50.24 and 759.5-2659.6 micrograms g-1 dry weight. Concentrations of zinc, aluminium and cadmium were higher in the oysters. The level of cadmium exceeded the National Health and Medical Research Council (NHMRC) recommended limit. In general, levels of these and other metals were higher near a bauxite treatment plant. PMID- 2326619 TI - Trends in heavy metal levels in the dissolved and particulate phase in the Dutch Rhine-Meuse (Maas) Delta. AB - Levels of the heavy metals Cd, Cr, Cu, Pb and Zn, in both the dissolved and particulate phase, were determined in two sampling campaigns in August 1978 and August 1984 in the Dutch Rhine-Meuse (Maas) Delta. Besides the heavy metal concentrations, other important parameters were determined, such as the concentrations of seston, chlorophyll and nutrients. The concentrations of dissolved Cd and of Cd, Pb and Cu in particulate matter were much higher in 1978 than in 1984, especially for Cd. This may be due to the strict regulations implemented in Germany to reduce the pollution of natural waters by heavy metals. The correlation between the high Cd content and the chlorophyll content is explained by the binding of Cd to living and dead organisms. The distribution of the metals between the dissolved and the particulate phase, indicated by the distribution quotient Kd, increases from low values of Kd for Cu and Zn, to higher values for Cd and Cr, and the highest values for Pb. The differences are explained by various binding forms of each of these metals in natural waters. PMID- 2326620 TI - Urinary 1-hydroxypyrene as an indicator of human exposure to ambient polycyclic aromatic hydrocarbons in a coal-burning environment. AB - Urinary 1-hydroxypyrene of residents of Beijing, Shenyang and Taiyuan, and workers at two coke plants, a steel plant and control groups was determined using high pressure liquid chromatography. Polycyclic aromatic hydrocarbons (PAHs) of airborne particulates from these cities and coke plants were analyzed using GC MS; chromatogram profiles, from which 15 chemical compounds were quantified, were similar. The percentage of pyrene and benzo[a]pyrene in PAHs was fairly constant. Statistical analysis showed significant correlation of urinary 1-hydroxypyrene with the concentration of pyrene and benzo[a]pyrene in the ambient PAHs; the correlation coefficient was 0.978 and 0.959, respectively. It is suggested that urinary 1-hydroxypyrene can be used as a biological monitoring index for human exposure to genotoxic PAHs from the burning of coal. PMID- 2326621 TI - Cadmium, copper, lead, and zinc concentrations in human scalp and pubic hair. AB - Cadmium, Cu, Pb, and Zn concentrations were measured in the first 3 cm of the proximal end of scalp hair and in pubic hair of 41 humans, by atomic absorption spectrometry. Data are presented as geometric means. Scalp hair (SH) metal levels were higher than those in pubic hair (PH), (Cd, 85.1 vs 60.8 ng g-1; Cu, 17.7 vs 11.9 micrograms g-1; Pb, 1.72 vs 1.05 micrograms g-1; Zn, 148.8 vs 133.3 micrograms g-1) with correlation coefficients of: Cd, r = 0.474; Cu, r = 0.549; Pb, r = 0.576; and Zn, r = 0.263. Further correlations were established between Cd and Pb levels (SH, r = 0.691; PH, r = 0.621) as well as between Cd and Zn levels (SH, r = -0.268). In PH the Cd, Cu, and Pb levels of males were higher than those of females, whereas the Zn levels were lower in SH and PH of males. Scalp hair Zn contents were inversely related to age. Cadmium and Pb levels in SH and PH were higher in summer than in winter, whereas the SH Zn contents were higher in winter. An influence of place of residence, smoking habit, hair colour and hair structure on SH and PH metal levels is identified. It is concluded that hair metal analysis in samples close to the scalp is not seriously invalidated by sources of external contamination. PMID- 2326622 TI - Selenium status of cancer patients in Greece. AB - The Se status of 177 Greek cancer patients has been assessed by fluorimetric analysis of the Se concentration in whole blood, urine (morning) and hair. Patients either with newly diagnosed cancers or with metastases or who are undergoing therapy have statistically significant less blood, urine and hair Se than age- and sex-matched healthy controls. There is a strong and significant correlation between blood and urine or hair Se in the newly diagnosed cancers. In cancers of systems involving absorption, metabolism and excretion of Se, and in female breast cancer, the Se levels in blood, urine and hair are significantly lower than in the controls. In cancers of the respiratory and haematologic systems, blood and urine Se are normal, while hair Se is significantly lower than in controls. The results are compared with literature data; conflicting data may be due to different dietary habits of the various populations. Some cancerous tissues, such as those of the peptic system, accumulate Se compared with their adjacent, apparently healthy tissues, but others, of the urinary system for example, do not. The reason(s) for this behaviour, however, is not known. PMID- 2326624 TI - Mercury, cadmium and lead concentrations in five species of freshwater fish from eastern England. AB - A total of 146 samples of five species of fish were examined between March and November 1986 in four sites from the Rivers Brett and Chelmer in eastern England. Variations in heavy metals concentrations between sites and species were related mainly to size differences of fish. Mercury levels in the flesh were higher than in the liver, while cadmium and lead levels were higher in the liver. PMID- 2326623 TI - Mercury, cadmium and lead in eels and roach: the effects of size, season and locality on metal concentrations in flesh and liver. AB - Mercury, cadmium and lead were measured in the liver and flesh of 885 eels and 338 roach collected from four sites on the Rivers Brett and Chelmer, eastern England, over the period November 1985 to November 1987. Concentrations of metals in liver and flesh of both species were highly correlated at all sites. Generally, mercury in flesh and liver was correlated with fish length in both species. There were fewer significant relationships between length and the concentrations of cadmium and lead. Site differences in mean concentrations were recorded. Seasonal variations in metal concentrations were largely restricted to eels from the more polluted Site 4. The significance of the concentrations of metals to the status of the fishery is discussed. PMID- 2326625 TI - Volatilization of selenium from agricultural evaporation pond sediments. AB - Microbial volatilization of Se was evaluated as a means of detoxifying Se contaminated sediments. Sediment samples containing 60.7 (Kesterson Reservoir) and 9.0 mg Se kg-1 (Peck ponds) were incubated for 273 days in closed systems located in the greenhouse. Volatile Se was collected from a continuous air exchange stream using activated carbon. Various economical and readily available organic and inorganic amendments were tested for their capacity to enhance the microbial process, including Citrus (orange) peel, Vitis (grape) pomace, feedlot manure, barley straw, chitin, pectin, ZnSO4, (NH4)2SO4, and an inoculum of Acremonium falciforme (an active Se methylating fungus). With the Kesterson sediment, the highest Se removal (44.0%) resulted from the combined application of citrus peel and ZnSO4, followed by citrus peal alone (39.6%), and citrus peel combined with ZnSO4, (NH4)2SO4 and A. falciforme (30.1%). Manure (19.5%), pectin (16.4%), chitin (9.8%) and straw plus N (8.8%) had less pronounced effects. Without the amendments, cumulative Se volatilization was 6.1% of the initial inventory. Grape pomace (3.0%) inhibited the process. With the Peck sediment, the highest amount of Se removed was observed with chitin (28.6%), manure (28.5%), and citrus peel alone (27.3%). Without amendments, 14.0% of the native Se was volatilized in 273 days. Cumulative Se volatilization was 24.7% with citrus plus Zn and N, 17.2% with citrus plus Zn, and 18.8% with citrus plus Zn, N and A. falciforme. Pectin (15.2%), straw plus N (16.4%), and grape pomace (7.3%) were among the less effective amendments for the Peck sediment. The differences in the effectiveness of each treatment between the two seleniferous soils may be a result of the residual N content of the sediments. With the Kesterson sediment, which was high in organic C and N, added N inhibited volatilization of Se, while with Peck sediments (low in organic C and N) N-rich materials tended to accelerate Se volatilization. Inoculation with A. falciforme did not enhance Se evolution from either sediment, indicating that there was a sufficient population of microflora capable of producing gaseous Se. PMID- 2326626 TI - Pollution by the fungicide pentachloronitrobenzene in an intensive farming area in Japan. AB - Environmental pollution by pentachloronitrobenzene (PCNB) was investigated at Tsumagoi, an intensive farming area, where a great amount of PCNB has been applied. High concentrations of PCNB were detected in river water near an area of cabbage cultivation. Further, pentachloroaniline (PCA) and pentachlorothioanisole (PCTA), which are the principal biodegradation products of PCNB, were also detected, and their ratios to PCNB were higher in autumn than in summer. PCNB concentrations in soil were similar to those of river sediment, in which PCNB was concentrated 5000-10,000 times over levels in river water. The biodegradation rate of PCNB in river water was higher than in river sediment and soil. The formation rates of PCA from PCNB were higher in river sediment and soil than in river water. It is considered that PCA remains for a long time in the environment and accumulates in river sediment and soil. PMID- 2326627 TI - Excitotoxic disorders. PMID- 2326628 TI - When commerce and academe collide. PMID- 2326629 TI - Pork in a medical wrapping. PMID- 2326630 TI - Conflict at the RAC. PMID- 2326631 TI - Getting together bit by bit. PMID- 2326632 TI - A FASEB sampler. American Societies for Experimental Biology. PMID- 2326633 TI - Primary sequence information from intact proteins by electrospray ionization tandem mass spectrometry. AB - Tandem mass spectrometry has been used to obtain information related to portions of the primary sequence for an intact protein, bovine ribonuclease A. Multiply charged molecular ions, generated by electrospray ionization, were collisionally dissociated at low energies in a triple quadrupole mass spectrometer to yield singly and multiply charged fragment ions that can be assigned to the known sequence of the protein. Dissociation of the highly charged molecular ions resulted in pairs of complementary product ions. The higher order (gas-phase) protein structure affects the dissociation processes, as observed in comparisons of tandem mass spectra of the native and disulfide-reduced forms of ribonuclease A. PMID- 2326634 TI - Indication of increasing solar ultraviolet-B radiation flux in alpine regions. AB - Measurements at the Jungfraujoch High Mountain Station (Swiss Alps, 47 degrees N, 3576 meters above sea level) indicate that there has been a slight increase of about 1 percent per year in the flux of solar ultraviolet-B radiation (290 to 330 nanometers) since 1981. A Robertson-Berger detector was used to measure solar erythemal radiation. The increase can be related to a long-term ozone depletion. PMID- 2326636 TI - A class I antigen, HLA-G, expressed in human trophoblasts. AB - The alpha chain of the human histocompatibility antigen HLA-G was identified as an array of five 37- to 39-kilodalton isoforms by the use of two-dimensional gel electrophoresis. Both cell-associated and secreted HLA-G antigens are prominent in first trimester villous cytotrophoblasts and are greatly reduced in third trimester cytotrophoblasts. Allelic variation was not detected, an indication that HLA-G is not obviously polymorphic in cytotrophoblasts. Among the following choriocarcinoma cell lines studied, HLA-G is expressed in JEG but not in Jar or BeWo. Expression of endogenous HLA-G genes has not been found in normal lymphoid cells. Thus, HLA-G is subject to both cell type-specific and developmental regulation and is expressed in early gestation human cytotrophoblasts. PMID- 2326635 TI - Phosphate-methylated DNA aimed at HIV-1 RNA loops and integrated DNA inhibits viral infectivity. AB - Phosphate-methylated DNA hybridizes strongly and specifically to natural DNA and RNA. Hybridization to single-stranded and double-stranded DNA leads to site selective blocking of replication and transcription. Phosphate-methylated DNA was used to interrupt the life cycle of the human immunodeficiency virus type-1 (HIV 1), the causative agent of acquired immunodeficiency syndrome (AIDS). Both antisense and sense phosphate-methylated DNA 20-nucleotide oligomers, targeted at the transactivator responsive region and the primer binding site, caused complete inhibition of viral infectivity at a low concentration. Hybridization of phosphate-methylated DNA with folded and unfolded RNA was studied by ultraviolet and proton nuclear magnetic resonance spectroscopy. The combined results of hybridization studies and biological experiments suggest that the design of effective antisense phosphate-methylated DNA should focus on hairpin loop structures in the viral RNA. For sense systems, the 5' end of the integrated viral genome is considered to be the important target site. PMID- 2326637 TI - Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina. AB - The organization of the visual cortex has been considered to be highly stable in adult mammals. However, 5 degrees to 10 degrees lesions of the retina in the contralateral eye markedly altered the systematic representations of the retina in primary and secondary visual cortex when matched inputs from the ipsilateral eye were also removed. Cortical neurons that normally have receptive fields in the lesioned region of the retina acquired new receptive fields in portions of the retina surrounding the lesions. The capacity for such changes may be important for normal adjustments of sensory systems to environmental contingencies and for recoveries from brain damage. PMID- 2326638 TI - Sodium-calcium exchange in excitable cells: fuzzy space. PMID- 2326639 TI - Stanford erupts over indirect costs. PMID- 2326640 TI - NIH: the endless search. PMID- 2326641 TI - Bromley promises small science focus. PMID- 2326642 TI - Scientific misconduct cases revealed. PMID- 2326643 TI - Is AIDS dementia due to increases in calcium? PMID- 2326644 TI - "Hairy enzymes" stay in the blood. PMID- 2326645 TI - AIDS meeting: visas. PMID- 2326646 TI - HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. AB - Coat protein gp120 from the human immunodeficiency virus type-1 (HIV-1) increased intracellular free calcium and injured rodent retinal ganglion cells and hippocampal neurons in culture. Highly purified recombinant gp120 envelope protein produced these effects in a dose-dependent fashion at picomolar concentrations. Immunoprecipitation with antibody to gp120, but not with control immunoglobulin-containing serum, depleted solutions of the viral envelope protein and also prevented both the rise in intracellular calcium and neuronal toxicity. The gp120-induced increase in intracellular calcium was abrogated by transiently lowering extracellular calcium or by adding the dihydropyridine calcium channel antagonist nimodipine (100 nM). Calcium channel antagonists also prevented gp120 induced neuronal injury. In addition, intracellular stores appeared to contribute substantially to the increase in calcium elicited by gp120. Since increases in intracellular calcium have been associated with neurotoxicity, it is possible that an injurious effect of gp120 on neurons might be related to this mechanism and that treatment with calcium channel antagonists may prove useful in mitigating HIV-1-related neuronal injury. PMID- 2326647 TI - Defective presentation of endogenous antigen by a cell line expressing class I molecules. AB - Cytotoxic T lymphocytes (CTLs) recognize class I major histocompatibility complex (MHC) molecules associated with antigenic peptides derived from endogenously synthesized proteins. Binding to such peptides is a requirement for class I assembly in the endoplasmic reticulum (ER). A mutant human cell line, T2, assembles and transports to its surface some, but not all, class I MHC molecules. The class I molecules expressed on the surface of T2 do not present peptides derived from cytosolic antigens, although they can present exogenously added peptides to CTL. The transported class I molecules may interact weakly with an unknown retaining factor in the ER such that they can assemble despite the relative shortage of peptides. PMID- 2326648 TI - Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. AB - The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [3H]thymidine demonstrated DNA cleavage in erythroid progenitor cells that was accompanied by DNA repair and synthesis. Erythropoietin reduced DNA cleavage by a factor of 2.6. In the absence of erythropoietin, erythroid progenitor cells accumulated DNA cleavage fragments characteristic of those found in programmed cell death (apoptosis) by 2 to 4 hours and began dying by 16 hours. In the presence of erythropoietin, the progenitor cells survived and differentiated into reticulocytes. Thus, apoptosis is a major component of normal erythropoiesis, and erythropoietin controls erythrocyte production by retarding DNA breakdown and preventing apoptosis in erythroid progenitor cells. PMID- 2326649 TI - Coagulation and cancer. PMID- 2326650 TI - Nutrient groove of the ilium, a subtle but important forensic radiographic marker in the identification of victims of severe trauma. AB - A variety of skeletal characteristics pertaining to the bony pelvis have, over the years, been of assistance as forensic markers, but the importance of the nutrient groove of the ilium has not been appreciated. During aircraft accident investigations we compared premortem anteroposterior abdominal radiographs with postmortem specimen radiographs of the ilium, with particular attention directed to the nutrient groove of the ilium. This marker can assume several configurations (i.e., parallel, V-shaped and Y-shaped) and is situated a few centimeters lateral to the sacroiliac joint. Left/right asymmetry, or absence of the nutrient grove on one side of the pelvis are possible variants within an individual. The purpose of this report is to emphasize the previously unrecognized importance of the nutrient groove of the ilium as a useful forensic radiographic marker. PMID- 2326651 TI - A comparison of radiographic and computer-assisted measurements of thoracic and thoracolumbar sagittal curvature. AB - Sagittal plane curve characteristics of the thoracolumbar spine were evaluated from 286 lateral chest radiographs comparing the Cobb technique with a computer aided digitizer. Thoracic kyphosis and curve apex were measured from the T3 to T11 segments, and in 120 cases, the level of the thoracolumbar curve inflexion point was determined. An age-related increase in curve magnitude was similar for both measurements, although computer generated kyphosis angles were generally larger. The apex of thoracic kyphosis was consistently located near T7 for males compared with greater variability with age for females. The thoracolumbar inflexion point shifted caudally with increasing years, being most marked for females. The computer method was more reliable, producing a coefficient of variation of 1.4% on repeated measurement. The ability to describe quantitatively the thoracolumbar curve characteristics, calculate angles between selected segments, determine points of inflexion and maximum curvature, indicates that radiographic evaluation of sagittal spinal curvature is improved with the use of computer-aided measurement. PMID- 2326652 TI - Osteoporosis: diagnosis by plain chest film versus dual photon bone densitometry. AB - Readers of chest radiographs often comment on the presence of osteoporosis. We have hypothesized that diagnoses of osteoporosis from chest films are not reliable even when made by experienced radiologists. To test this hypothesis, we had nine radiologists estimate the degree of bone density seen on 45 lateral chest films. We compared their estimates of bone density to the results of dual photon bone densitometry of the lumbar spine. We found that there was little ability to accurately diagnose osteoporosis by chest film since the group of nine readers achieved accuracies ranging from 0.59 to 0.64. Therefore, we feel it is unjustified to comment upon the presence or absence of osteoporosis on the basis of chest films. PMID- 2326653 TI - Metastatic neuroblastoma: new abnormalities on bone scintigraphy may not indicate tumour recurrence. AB - Neuroblastoma is a potentially curable childhood malignancy with survival rates of 20% reported even in advanced disease. Technetium-labelled methylene diphosphonate (Tc99m-MDP) scanning is well established as a method of assessing bone disease. We report four patients, with advanced neuroblastoma in complete or partial remission, in whom new abnormalities on bone scintigraphy were due to benign lesions. Correct management depends on the precise diagnosis of such lesions. PMID- 2326654 TI - The diabetic foot: magnetic resonance imaging evaluation. AB - Fourteen diabetic patients with suspected foot infection and/or neuropathic joint (Charcot Joint) were evaluated with magnetic resonance imaging (MRI) in an attempt to assess the extent of the infection and also to distinguish infection from the changes seen with neuroarthropathy. The majority of patients with infection had more than one site of involvement and the following diagnoses were made by MRI evaluation: osteomyelitis (n = 8), abscess (n = 7), neuropathic joint (n = 5), septic arthritis (n = 4), and tenosynovitis (n = 4). Clinical or surgical/pathological confirmation of the MRI diagnoses was obtained in all but nine sites of infection or cases of neuropathic joint. If the two diagnostic categories of septic arthritis and tenosynovitis are excluded, all but four of the MRI diagnoses were confirmed. A distinctive pattern for neuroarthropathy was identified in five cases, consisting of low signal intensity on T1- and T2 weighted images within the bone marrow space adjacent to the involved joint. We conclude that MRI is a valuable adjunct in the evaluation of the diabetic foot, and that it provides accurate information regarding the presence and extent of infection in this subset of patients. MRI has proven particularly helpful in differentiating neuroarthropathy from osteomyelitis. PMID- 2326655 TI - Growing bone cysts in long-term hemodialysis. AB - All patients with chronic renal failure undergoing hemodialysis for more than 10 years in the university hospitals of Leuven were selected for this study. The medical records and radiographs of these 21 patients were studied retrospectively. Skeletal surveys were examined for the presence and location of subchondral cysts. The predialysis films and the films taken after 5, 10, 15 and 20 years of dialysis were reviewed. Subchondral cysts that grew in size and number were found in the wrist, humeral head, hip, and patella. Accurate measurements were made of cysts in the wrist and compared with a control group. In the dialysis group, cystic involvement of the wrist was more common and the size and number of the cysts were larger. Soft tissue swelling was seen in the dialysis group but not in controls. Soft tissue swelling was assessed on shoulder radiographs by measuring the acromiohumeral distance (ACD) and in the knees by ultrasonic measurement of synovial thickness. In 11 patients synovial or bone biopsies or aspirated synovial fluid were available. All these patients had swollen joints and multiple subchondral periarticular cysts. Amyloid deposition was found in ten of these patients, and this proved to be composed of B2 microglobulins in seven. PMID- 2326656 TI - Case report 571: Radiation-induced growth abnormalities. AB - A case of a 23-year-old man with deformities of the spine and hip is presented, demonstrating the bizarre long term effects of radiation on developing bone. The spectrum of radiation-induced growth abnormalities is reviewed. Multiple variables, including age of the patient, the quantity of radiation delivered, and the site of delivery, all effect the eventual radiographic appearance. PMID- 2326657 TI - Case report 587: Adamantinoma of the tibia mimicking osteofibrous dysplasia. AB - This case emphasized that the differential diagnosis of osteofibrous dysplasia and adamantinoma of the tibia can be difficult on roentgengrams as well as on histological studies. A radiological and histological diagnosis of osteofibrous dysplasia of the tibia in a young adult should always raise the consideration of the possibility of an adamantinoma, and in the correlation of the radiological features with the biopsy findings it is very important to gain representative tissue material for establishing the correct diagnosis of adamantinoma. PMID- 2326658 TI - Case report 588: Intracortical chondroma of the left femur. AB - A case of intracortical chondroma in the left femur in a 22-year-old man is presented. Proof was obtained by open biopsy. The issue of periosteal vs intracortical chondroma was discussed in depth, with emphasis on the radiographic appearances. The differential diagnosis of this benign intracortical lesion was also included. The histopathologic characteristics of this intracortical chondroma were described and a possible explanation for the unusual location of the cartilage lesion within the cortex was considered. PMID- 2326659 TI - Case report 589: Use of Ostamer in fusion of lumbar spine, postoperative appearance. AB - In the late 1950s and early 1960s there was intense orthopedic interest in a plastic polyurethane foam (Ostamer) that could be used in the fixation of fractures, performance of arthrodesis, and in spinal fusions. It saw limited success at that time but eventually fell from favor. A patient presenting with a draining sinus in the buttock, back pain, and a history of lumbar spinal fusion with Ostamer was recently scanned in our department. The CT appearance of Ostamer and a brief review of the literature are reported. PMID- 2326660 TI - Case report 590: Diffuse pigmented villonodular synovitis with a cartilaginous component. AB - The authors present the case of a patient 54 years of age who developed well defined osteolysis in the distal end of the humerus, with a slight radiodensity in the soft tissue. The radionuclide scintigram and above all the CT, were useful in defining the characteristics and expansion of the mass more precisely. Surgical intervention and histological examination demonstrated a seemingly unique case of PVNS of the elbow with diffuse cartilaginous components and erosion of the distal end of the humerus. The pathological findings in this unusual case, actually suggested the possibility of an intermediate form of PVNS associated with synovial chondromatosis. PMID- 2326661 TI - Case report 591: Osteoarthrosis (OA) of hip associated with microscopic gouty tophi. AB - It has been demonstrated in this 58-year old woman that osteoarthrosis OA coexisted in a hip with microscopic gouty tophi. It is demonstrated that the bone erosions around the hip in this case were due to OA and not gouty arthritis. It is believed that OA is not a consequence of gout and that such an association between gout and OA is exceptional. It is maintained that a true association exists between OA and ochronosis while a relationship may exist between OA and chondrocalcinosis, but the nature of this relationship is not clear. PMID- 2326662 TI - Case report 592: Bone graft donor site of tibia. AB - A case is presented in which a donor site for a bone graft from the proximal end of the tibia caused diagnostic difficulty. The bony defect produced in such procedures is easily confused with a variety of neoplastic and neoplasm-like lesions. The clinical history, use of immediate postoperative films, and knowledge concerning the common sites for obtaining bone graft donor tissue are critical in offering the correct diagnosis. PMID- 2326663 TI - Case report 593: Hemangioma of sternum. AB - A 38-year-old woman presented with an expansile lesion of the sternum. Plain film tomograms and computed tomography showed an expansile lesion of the sternum. Bone scanning revealed increased uptake in the sternum. The neoplasm was surgically excised and proved to be a hemangioma (Fig. 4a) and 4b). The rarity of this neoplasm in the sternum was stressed. An extensive search of the literature failed to reveal a single previous report of a sternal hemangioma. A differential list of other primary benign and malignant sternal tumors was presented. PMID- 2326664 TI - Case report 594: Osseous sarcoidosis (osteolytic) of lumbar spine and pelvis. AB - A case of destructive osseous sarcoidosis involving the lower lumbar spine, sacrum, and pelvis has been presented. The pattern of multiple small lytic lesions without sclerosis in this distribution has not been described previously. Identification of these lesions was only possible by computed tomography and differentiation from metastatic disease required open biopsy. PMID- 2326665 TI - [Dermatologic antiseptics]. PMID- 2326666 TI - [Hyper-hypothermia. Some ways to control them]. PMID- 2326667 TI - [Multiple hospitalizations. How to perform a nursing follow-up]. PMID- 2326668 TI - [Interleukin 2. Nursing care protocol]. PMID- 2326670 TI - [Care and hygiene. Implementation in a diabetic service]. PMID- 2326669 TI - [Let's improve the discharge]. PMID- 2326671 TI - [The function of quality control in a health care unit]. PMID- 2326672 TI - [Implementation of a nursing research project. General introduction]. PMID- 2326674 TI - [Gerstmann-Straussler-Scheinker disease]. PMID- 2326673 TI - [Central nervous system diseases caused by unusual viruses. General facts]. PMID- 2326675 TI - [Alzheimer's disease]. PMID- 2326676 TI - [Nursing care in Alzheimer's disease]. PMID- 2326677 TI - [Treatment of bedsores and trophic wounds with an absorbent dressing]. PMID- 2326678 TI - [Nursing school directors and general nurses in public hospitals. New statutes]. PMID- 2326679 TI - [The nursing process. A nursing student evaluation tool]. PMID- 2326681 TI - [Community mental health nurses. Demography]. PMID- 2326680 TI - [Acute paralysis of the right arm]. PMID- 2326682 TI - [Community mental health services and medico-social organizations. The role of the nurse]. PMID- 2326683 TI - [Active adults and passive adolescents]. PMID- 2326684 TI - [Professional practice]. PMID- 2326685 TI - [Psychiatric nurses and special education teachers. Overlapping areas]. PMID- 2326686 TI - [Training. A big difference between education and instruction]. PMID- 2326687 TI - [Education of community mental health nurses]. PMID- 2326688 TI - [The mental health nursing profession. Future and context]. PMID- 2326690 TI - [Psychoanalysis, a required frame of reference]. PMID- 2326689 TI - [A common frame of reference: psychoanalysis? Realizing that everyone is a fellow being]. PMID- 2326691 TI - [The emergence of the social professions]. PMID- 2326692 TI - Spinal metastases: the obvious, the occult, and the impostors. AB - Spines from 832 deceased patients with a terminal diagnosis of malignant neoplasm were examined grossly, microscopically and radiographically for evidence of tumor. Gross tumor and bone destruction or sclerosis were reliable signs of obvious metastases. Occult lesions visualized on gross sagittal sections but not detectable radiographically occurred in 26% of spines with confirmed metastatic deposits. Vertebral collapse was not a reliable indicator of metastases. Collapse was not caused by neoplasm in 22% of cases. Overall, metastases were found in 36% of patients dying from neoplastic disease. Although most metastases are obvious, occult lesions not visible radiographically occur. Collapsed vertebra may be impostors simulating metastatic disease. PMID- 2326693 TI - Accuracy of pedicular screw placement in vivo. AB - The accuracy of pedicular screw placement was assessed in 40 consecutive patients treated with the AO "Fixateur Interne." Postoperative CT scans were used to measure canal encroachment from the medial border of the pedicle, the angle of insertion and the point of entry. Eighty-one percent of the screws were placed within 2 mm of the medial border of the pedicle and 6% had 4-8 mm of canal encroachment with two patients developing minor neurological complications that spontaneously resolved. Four percent were inserted lateral to the pedicle. The parameters linked to satisfactory screw placement include entry point, angle of insertion and pedicular isthmus widths. Improvement in accuracy was noted in the latter 25% of screw insertions, reflecting the learning curve associated with this technique. PMID- 2326694 TI - Multiaxis cyclic biomechanical testing of Harrington, Luque, and Drummond implants. AB - The performance characteristics of Harrington-Moe distraction rods, paired wired Luque rods and Drummond's system were evaluated and compared when subjected to nondestructive cyclic, multidirectional biomechanical testing. Twelve fresh, frozen swine spines with intact facet joints and anterior and posterior ligamentous complexes were instrumented and tested in a specially designed pneumatic testing machine. The instrumented spines were subjected to 207 kN/m2 compression and 49 N-m torsion. Each spine was cycled 28,000 times at 1 cycle per second. Linear and angular displacements were determined by digitizing photographs and video tapes made during testing. A computer program developed and refined for the project was used to complete the data analysis. Approximately 540 items of angular and linear displacement data were collected for each spine. Inspection of the spines after cyclic, multidirectional testing revealed no change in their osteoligamentous integrity compared with pre-testing. Pre- and post-testing radiographs showed no evidence of osseous failure, hook dislodgement or wire breakage. Erosion of laminal bone at the Harrington hook attachment sites was observed. Displacement of the Harrington hooks was seen during off-axis compression-torsion testing. Fretting and deposit of metal wear debris occurred between the sublaminal wires and "L" rods. There was no evidence of loosening of either the Drummond or Luque implants or fatigue failure of any component. Analysis of the linear and angular displacement data showed that the Luque and Drummond instrumented spines displaced less in axial compression, off-axis compression and off-axis compression-torsion than the single Harrington-Moe distraction rod.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326696 TI - Surgical management of severe cervical kyphosis following extensive laminectomies. PMID- 2326695 TI - Incidence of lumbar disc surgery. A population-based study in Olmsted County, Minnesota, 1950-1979. AB - Age- and sex-specific incidence rates of operation for suspected lumbar disc prolapse were determined for residents of Olmsted County, Minnesota, for the 30 year period 1950 through 1979. The incidence rate (adjusted to the age and sex distribution of the United States white population in 1980) was 52.3 per 100,000 person-years for all such operations and 46.3 per 100,000 person-years for initial operations. These rates remained fairly constant over the study period. A distinction was made between surgically proven and unproven cases of lumbar disc prolapse. Patients with a surgically proven lumbar disc prolapse had about 10 times the risk of another operation for disc prolapse within 10 years after the first operation compared with the general population. PMID- 2326698 TI - Scoliosis and juvenile rheumatoid arthritis. A case report of surgical treatment. PMID- 2326697 TI - Guillain-Barre syndrome following spinal fusion for adult scoliosis. PMID- 2326700 TI - Further minification of the Taylor retractor for lumbar surgery. Technical note. PMID- 2326699 TI - Lumbar disc protrusion in an acromegalic patient. PMID- 2326701 TI - Nonoperative treatment of neuropathic spinal arthropathy. PMID- 2326702 TI - Spinal cord response to laser treatment of injured peripheral nerve. AB - The authors describe the changes occurring in the spinal cord of rats subjected to crush injury of the sciatic nerve followed by low-power laser irradiation of the injured nerve. Such laser treatment of the crushed peripheral nerve has been found to mitigate the degenerative changes in the corresponding neurons of the spinal cord and induce proliferation of neuroglia both in astrocytes and oligodendrocytes. This suggests a higher metabolism in neurons and a better ability for myelin production under the influence of laser treatment. PMID- 2326703 TI - Diurnal changes in straight leg raising. AB - Diurnal changes in straight leg raising were measured in 28 patients with criteria of lower lumbar disc protrusion, having first established an acceptable intra-observer repeatability using an oil-filled precision goniometer. Eight patients showed little change between the straight leg raising after a night of recumbancy, and after 180 minutes in the upright posture. Twenty patients, however, had 10 or more degrees of improvement in straight leg raising, with a mean improvement of 16.9 degrees (SD 7.1 degrees); most of the increase occurred in the first hour of being upright. The measurement returned again to the base level after 120 minutes of further recumbancy. Five of the eight patients who showed little diurnal change had discectomy, and four had a complete annular tear. Only one of the 20 patients with more than 10 degrees of diurnal change required surgery. Diurnal change in straight leg raising is probably related to the disc's proteoglycan content, its hydration, the tension of the protrusion and the presence of intact peripheral annular fibers. PMID- 2326704 TI - Discs degenerate before facets. AB - The purpose of this study was to determine the relationship between facet joint osteoarthritis and disc degeneration in subjects in whom both MRI and CT scans had been obtained. The MRI scans were used to determine disc degeneration, the CT scans to determine facet joint osteoarthritis. It was hypothesized that disc degeneration would sometimes occur without the presence of facet joint osteoarthritis, but that facet joint osteoarthritis would only occur in the presence of disc degeneration. Sixty-eight sets of scans were included and 330 discs and 390 facet joints were evaluated. There were 144 degenerated discs and 41 levels with facet osteoarthritis. Disc degeneration without facet osteoarthritis was found at 108 levels, while all but one of 41 levels with facet degeneration also had disc degeneration. That one exception occurred in a patient with advanced Paget's disease. Disc degeneration and facet osteoarthritis both were found to increase with increasing age. There was no difference between women and men. Degeneration at the L4-5 and L5-S1 levels was significantly more prevalent than at the L3-4 levels, while degeneration at the L3-4 level was significantly more common than at the L1-2 and L2-3 levels. We conclude that disc degeneration occurs before facet joint osteoarthritis, which may be secondary to mechanical changes in the loading of the facet joints. PMID- 2326705 TI - Radiographically detectable degenerative changes of the lumbar spine among concrete reinforcement workers and house painters. AB - In this study of lumbar degeneration and the role of mechanical loading in its development, lateral lumbar radiographs of 216 concrete reinforcement workers and 201 house painters aged 25-54 years were examined. Disc space narrowing occurred at about 10 years and spondylophytes at about 5 years younger age in the former than in the latter group. Risk ratios (RR) were estimated from the regression coefficients of logistic regression models. RR for the univariate effect of occupation on disc space narrowing was 1.8, and adjustment for age, earlier back accidents, height, body mass index and smoking had only a minor effect on this relationship, adjusted RR 1.8. The crude RR for spondylophytes was 1.5, and the adjusted RR 1.6. Earlier back accidents showed a significant univariate relationship with DSN, but in multivariate analysis this variate did not retain its significance. It was concluded that heavy physical work enhances the degenerative process of the lumbar spine. Materials handling and postural loading are proposed to be occupational factors of importance in the development of both disc space narrowing and spondylophytes. PMID- 2326706 TI - Relation between form and function in the sacroiliac joint. Part I: Clinical anatomical aspects. AB - Observations on sectioned and opened preparations of human sacroiliac joints (SI joints) show the presence of cartilage-covered ridges and depressions, which are complementary on the auricular surfaces. These macroscopically visible features of the joints, which become visible relatively early in life, are more pronounced in men than in women. This type of roughening, as well as that by increased coarseness of the auricular surface, is viewed as a nonpathologic adaptation to the forces exerted at the SI joints, leading to increased stability. Differences between men and women may be attributed to childbearing and to a difference in the center of gravity. It is emphasized that intra-articular ridges and depressions can be misinterpreted roentgenologically as osteophytes. PMID- 2326707 TI - Relation between form and function in the sacroiliac joint. Part II: Biomechanical aspects. AB - The amount of friction between the articular surfaces of sacroiliac (SI) joints was determined and related to the degree of macroscopic roughening. Results show that articular surfaces with both coarse texture and ridges and depressions have high friction coefficients. The influence of ridges and depressions appears to be greater than that of coarse texture. The data are compatible with the view that roughening of the SI joint concerns a physiologic process. PMID- 2326708 TI - Primary tumors of the axial skeleton. Experience of the Leeds Regional Bone Tumor Registry. AB - Primary tumors of the axial skeleton are rare and a survey of the Leeds Regional Bone Tumor Registry found them to constitute only 55 of the 1950 cases (2.8%). Chordoma was the most frequent tumor in the cervical and sacral regions as well as the most common diagnosis overall and osteosarcoma ranked second. Pain was the most frequent presenting symptom but over half the patients developed some neurological abnormality. In spite of treatment survival was poor in patients with malignant lesions or neurological involvement. The establishment of Bone Tumor Registries is the only way that sufficient data on large numbers of these rare tumours can be amassed to provide a valuable and otherwise unavailable source of information for research, education and service. PMID- 2326709 TI - A case report of recurrent osteoblastoma of the rib presenting as painless progressive scoliosis. PMID- 2326710 TI - Progressive sacral nerve root dysfunction, a possible complication of sublaminar hooks. A case report. PMID- 2326711 TI - The CT appearances of arachnoiditis ossificans. PMID- 2326712 TI - Handedness and scoliosis convexity: a reappraisal. AB - The handedness of 254 girls with idiopathic scoliosis, minimum age eight years at diagnosis, attending Our Lady's Hospital was related to their scoliosis convexity. Curve patterns were assigned to right or left on the basis of the convexity of the low thoracic component only, regardless of primary curve. The curve pattern matched handedness in 82%. Of 228 right-handed children, 197 had a right convex curve pattern; of 26 left-handed children, 12 had a left convex pattern. The correlation between scoliosis configuration and handedness was statistically significant. This is in contrast to the findings of previous studies, which have considered convexity only, without reference to the configuration of the whole spine. The implication of this finding is that scoliosis is associated with cortical functions. PMID- 2326713 TI - Zinc status in patients with idiopathic scoliosis. AB - The zinc content in m. sacrospinalis, hair, leukocytes of peripheral blood, and in serum was examined in 50 patients with idiopathic scoliosis treated by Harrington instrumentation. A control group included 20 patients treated for spinal column injury. A significant decrease of zinc content in back muscles was observed in patients with scoliosis. The value of zinc in hair, leukocytes, and serum did not differ compared with the control group. Similarly, the potassium and magnesium content in muscle was the same in both groups. These results do not suggest that there is a primary zinc deficiency in patients with idiopathic scoliosis. The authors consider the decreased zinc content in back muscle of patients with idiopathic scoliosis to be a secondary disturbance associated with primary deformation of the spinal column. PMID- 2326714 TI - End vertebra angle--a roentgenographic method to describe a scoliosis. A follow up study of idiopathic scoliosis treated with the Boston brace. AB - A new method of measuring the range of the lateral deviation of a scoliosis is introduced. Here the Cobb angle is divided into two separate parts, consisting of the angles between each end vertebra and the horizontal plane. This angle is called the end vertebra angle. One hundred and twenty-one patients with adolescent idiopathic scoliosis, treated with Boston braces, were measured according to this technique and these angles were compared with the Cobb angles. All patients had S-shaped, right convex thoracic and left convex lumbar scolioses. Three end vertebra angles were measured and called A, B, and C. The middle end vertebra angle (B) was responsible for the improvement of the scoliosis in the brace, measured according to Cobb, and also the remaining improvement 2 years after weaning from the brace. The proximal and distal end vertebra angles (A and C), however, were unchanged or had increased at the time of the follow-up study 2 years after weaning from the brace treatment when compared with the status before the treatment. This could not be observed by using the Cobb method only. If end vertebra angles A and B are not equal, the thoracic curve is asymmetric. This asymmetry can be of two types depending on which of the two end vertebra angles is the greater one. If A is greater than B, the result of brace treatment was more successful than that of the symmetric curves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326715 TI - The Dwyer procedure in the treatment of idiopathic scoliosis. A 10-year follow-up review of 21 patients. AB - Despite the well-known Dwyer procedure, developed in 1969, comprehensive reports on its use, with long-term follow-up, are relatively scarce. The purposes of this study were to detect eventual late complications and to compare late results with postoperative angular curve correction. This article reports on 21 children operated on between October 1972 and October 1975 and reviewed with a minimum follow-up of 10 years (10 other patients were lost to follow-up after 5 years). Patients had idiopathic lumbar or thoracolumbar curves (average curve, 56 degrees). Results are discussed with a special reference to longitudinal observation. There is a great correction of the instrumented curve (postoperative, 5 degrees), but a loss of correction of 10 degrees is generally observed, prevented by a complete immediate correction or even hypercorrection. The upper curve, noninstrumented, also shows improvement (mean preoperative, 38 degrees; postoperative, 22 degrees; 10 years, 22 degrees) but re-equilibration cannot be predicted. Pseudarthrosis of one intervertebral space occurs frequently, and may cause failure of the cable with a loss of correction of 10-20 degrees. Kyphosis (or simple loss of lumbar lordosis) is commonly observed but should be balanced with correction of rotation. The following conclusions were made: morbidity is not severe, despite the advanced surgical technique. The technique is difficult and has a direct consequence on the quality of results; pseudarthrosis is a frequent complication, followed by important loss of correction; indications should be discussed carefully in idiopathic lumbar and thoracolumbar curves. It is still too early to advocate either anterior instrumentation of Zielke (VDS) or segmental posterior instrumentation (C. D. Luque) because of short-term follow-up. PMID- 2326716 TI - An analysis of the effect of the Zielke operation on the rib cage of S-shaped curves in idiopathic scoliosis. AB - This report evaluates the rib cage in 16 patients with S-shaped idiopathic scoliosis having the Zielke operation and followed-up for an average period of 30 months. Methods used include Cobb angle and a segmental evaluation (T7-T12) of each of convex and concave rib-vertebra angles (RVAs), rib-vertebra angle differences (RVADs), vertebral rotation, tilt and displacement. Preoperatively, the apical convex ribs droop more than the concave ribs, but the most striking difference is an asymmetry of RVAs, with increasing droop of the concave RVAs from T7-T12. The effect of the Zielke operation (on the lower curve) is: (a) to correct the Cobb angle, vertebral tilt, and displacement of the upper (thoracic) curve; (b) to derotate the spine; (c) to elevate the mobile concave ribs; (d) to have little or no effect on the stiff apical convex ribs; and (e) to increase the droop of the mobile lower convex ribs. During follow-up, six of the upper (thoracic) curves progressed. The apical RVAD and apical convex RVA are not prognostic. The concave RVAs maintain their position while convex RVAs elevate relative to the concave ribs. PMID- 2326717 TI - Three-dimensional analysis of neck motion. A clinical method. AB - A clinical method is described for simultaneous recording of neck motion in three different planes using electrogoniometric equipment. Results correlated with those reported in the literature regarding separate examinations of the motion range in the separate planes. Correlation with conventional gravity goniometer was good as to flexion-extension and lateral flexion, whereas, for rotation, a compass goniometer showed poor correlation and, also, unsatisfactory reproducibility. The electrogoniometric recordings showed good correlation with radiographically determined flexion-extension occiput-C7 as well as lateral flexion C1-T1. Graphical recordings made in the three different planes demonstrated in detail the different movements that contribute to the complex motion pattern of the neck. This three-dimensional motion analysis affords a more objective functional evaluation of common neck disorders that may supplement radiographic examination. PMID- 2326718 TI - Surgical treatment of the elderly patient with gynecologic cancer. AB - One hundred and one patients with gynecologic oncologic disease who were 70 years of age or more underwent 169 surgical procedures during an eight year period. The rate of major morbidity was 22.0 per cent, and the operative mortality rate was 1.3 per cent. The one year survival rate was 86 per cent. We were unable to predict morbidity or mortality based on age, past history, American Society of Anesthesiologists class, preoperative laboratory studies or type of operation. When the group of elderly patients was compared with a control group of patients with cancer who were 60 years of age or less, there was a significantly higher rate of major morbidity in the elderly (22 versus 9 per cent), but more one year survivors (86 versus 74 per cent). We conclude that age alone should not be a deterrent to surgical management of gynecologic malignant disease. With careful perioperative management and attention to the unique problems of the elderly, acceptable surgical rates can be achieved. PMID- 2326719 TI - Zero operative mortality rate in 109 consecutive elective aortic operations performed by residents. AB - One hundred and nine consecutive elective abdominal aortic operations were performed at the Veterans Administration Medical Center San Diego between 1984 and 1987. All of the operating surgeons were residents in general surgery who were assisted by attending staff. The mean age of the patients was 66.1 years and 34 patients were 70.0 years or older. The indication for operation was aortic aneurysm in 69 and aortoiliac occlusive disease in 40. Fifteen patients underwent highly complex procedures. The mean duration of operation was 5.6 hours, mean aortic clamp time was 72 minutes and mean volume of blood replacement was 1,186 milliliters. There was no operative mortality. Twenty-nine patients had 32 nonfatal complications. Patency of the graft was 100 per cent at discharge. We conclude that excellent clinical results with complex elective aortic operations can be achieved by surgical residents with appropriate supervision. PMID- 2326720 TI - Electromyographic evaluation of the gastrointestinal tract in patients with chronic Roux-en-Y limb. AB - Recently, a Roux-en-Y stasis syndrome was described in a few patients after gastric operations. Although the clinical long term results are usually good, the motility of Roux-en-Y biliary limb has not been evaluated yet. In the present study, we report electromyographic studies of the gastrointestinal tract of two patients with chronic Roux-en-Y hepaticojejunostomy. These two patients provided a unique opportunity to evaluate the electromyographic activity of chronic Roux en-Y limb in humans after one to five years. Seven pairs of bipolar extracellular electrodes were implanted in the antrum, duodenum, proximal part of the jejunum (15 centimeters proximal to the jejunojejunostomy), distal part of the jejunum (15 centimeters distal to the jejunojejunostomy), ileum, proximal Roux-en-Y limb and distal Roux-en-Y limb. All four phases of the migrating motor complex (MMC) were identified in the antrum and small intestine, including the Roux-en-Y limb, almost simultaneously to phase III in the duodenum. In the other two recordings (25 per cent), there was no relationship between phase III in the Roux-en-Y limb and that in the duodenum. Ingestion of food caused substitution of the MMC by the fed activity pattern in all recordings in the antrum and small intestine, including the Roux-en-Y limb. The findings of the present study indicate that the electromyographic activity of the Roux-en-Y limb may remain normal during fasting and fed states even many years after its creation. PMID- 2326721 TI - The natural history of pancreatic pseudocysts documented by computed tomography. AB - The clinical courses of 75 patients with pancreatic pseudocysts documented by computed tomography (CT) were retrospectively reviewed. History, physical examination, laboratory findings and CT scan data were analyzed. The treatment regimen followed during the period spanning the review dictated nonoperative management for those patients with asymptomatic pseudocysts who were able to tolerate oral intake. Operative management was used only for patients with persistent abdominal pain or enlargement or complications of pseudocyst. Approximately one-half of the patients (n = 36, 48 per cent) were managed nonoperatively, and the remainder (n = 39, 52 per cent) were treated operatively. In the group managed nonoperatively, with a mean follow-up period of one year, 60 per cent had complete resolution of the pseudocyst documented roentgenographically, and 40 per cent had pseudocysts that remained stable or decreased in size. Only one pseudocyst-related complication developed in the nonoperative group. No pseudocyst-related mortality occurred in either group. The size of the pseudocyst was a significant predictor of the need for operative drainage. Pseudocysts greater than 6 centimeters in diameter required surgical treatment in 67 per cent, significantly more frequently (p less than 0.05) than the 40 per cent of patients who required operative treatment for pseudocysts less than 6 centimeters in diameter. We conclude that a large proportion of patients with pancreatic pseudocysts, without specific indications for operative treatment, can be safely managed nonoperatively, with careful clinical and roentgenographic follow-up study. PMID- 2326722 TI - Treatment of fistulas of the biliary tract by endoscopic insertion of endoprostheses. AB - Five patients with fistulas of the biliary tract are reported; three had fistulas caused by operative injury and two, by accidental blunt abdominal trauma. All patients were treated successfully by endoscopic transpapillary insertion of biliary endoprostheses. The endoprostheses were removed after four to 17 weeks in all patients, and no evidence of biliary leakage was revealed by repeat cholangiograms and other clinical follow-up study. This effective, simple and safe method allows the fistula to heal and is a good alternative to surgical treatment. PMID- 2326723 TI - Endoscopic balloon dilation of the pylorus after esophagogastrostomy without a drainage procedure. AB - The necessity to perform a drainage procedure after esophagectomy using the stomach for substitution remains controversial. Transection of the pyloric sphincter may cause severe and debilitating gastroesophagitis because of increased duodenogastric reflux. Omitting the drainage procedure may lead to gastric stasis. In the patient group we studied (n = 50), 42 had partial esophagogastrectomy and intrathoracic esophagogastrostomy, 12 with and 30 without a drainage procedure. Eight had total thoracic esophagectomy and cervical esophagastrostomy using the entire stomach without a drainage procedure. Gastric stasis was not observed in the 12 patients with a drainage procedure, but in six, duodenal reflux gastroesophagitis caused considerable morbidity. This complication was seen only once in the group (n = 38) who did not have a drainage procedure. Four of the 38 patients with an intact pylorus (one patient after partial esophagogastrectomy and three patients after total thoracic esophagectomy) showed persistent pyloric closure. However, this complication was successfully managed by endoscopic balloon dilation under fluoroscopic survey. The results suggest that, after esophagectomy, the integrity of the pyloric sphincter should be preserved, since the complication arising from this policy can be simply managed by endoscopic balloon dilation. PMID- 2326724 TI - The impact of universal screening for gestational glucose intolerance on outcome of pregnancy. AB - Universal screening for gestational glucose intolerance has strong support, despite the lack of scientific evidence documenting its benefit. In the early 1980s, practicing obstetricians were split concerning the clinical importance of gestational glucose intolerance, so that some practitioners tested virtually all the patients they treated while others tested none. This historical reality provided concurrent screened and unscreened populations in whom to assess the impact of screening. We studied all 1,307 singleton pregnancies cared for and delivered at the New York Hospital-Cornell University Medical Center during a five month period. Large infants (birth weight greater than or equal to 4,000 grams) were born to 10.5 per cent of the women who were not screened (533) and to 11.2 per cent of the women who were screened (774). The process of screening not only failed to decrease the rate of large infants, but also failed to improve otherwise pregnancy outcomes and was associated with more intensive surveillance during pregnancy and a significantly higher rate of primary cesarean delivery. Given the unexpected concomitants of the screening process, we conclude that recommendations for universal screening for gestational glucose intolerance should be reconsidered. PMID- 2326725 TI - An easy and safe modified method of endoscopic balloon dilation for postgastrectomy anastomotic stricture. AB - An easy and safe modified method for endoscopic balloon dilation was performed 24 times for 16 patients who had undergone subtotal gastrectomy without any ensuing complications. The balloon dilator was simply attached to the ultraslender forward-viewing fiberscope just above the flexible portion. The balloon dilator can be easily placed into the stricture by advancing the fiberscope into the duodenum under direct vision. The present technique is particularly useful for the tortuous stricture of B-I anastomosis after a surgical procedure for carcinoma of the stomach, as opposed to using the conventional bougie or previous balloon techniques. This method may also be useful for other kinds of complicated stricture of the upper or lower part of the gastrointestinal tract. PMID- 2326726 TI - A technique for evaluation of the injured extremity with single film exclusion arteriography. AB - Single film exclusion arteriography is a simple technique for accurate evaluation of the vascular integrity of the extremity that has been traumatized which takes only minutes to perform. The procedure can be used to detect or exclude a vascular injury when obvious clinical signs of vascular disruption are absent but the mechanism of injury is suspicious. It also eliminates the delay and danger of formal angiography in select critically injured patients. Single film exclusion arteriography is an important diagnostic tool which can accurately delineate the presence of vascular trauma necessitating operative repair. PMID- 2326727 TI - The posterior fundoplasty in the treatment of gastroesophageal reflux. AB - The fundoplasty in the treatment of gastroesophageal reflux is essentially a modification of the Nissen fundoplication with the same percentage of effectiveness in the control of reflux but with a lower rate of undesirable side effects. The procedure is easy to perform. The author has performed this procedure more than 1,500 times within the last 20 years with very satisfactory results. PMID- 2326728 TI - Effect of early operation on cerebral vasospasm. AB - The effect of early operation on cerebral vasospasm was studied in 150 patients with aneurysmal subarachnoid hemorrhages who fulfilled all of the following criteria: admission by day 2 after subarachnoid hemorrhage, no rebleeding, clinical grades I to IV on admission, subarachnoid hemorrhage alone on computed tomography scan, not operated on between days 4 and 20, and availability of bilateral carotid angiograms done by day 2 and redone between days 7 and 9. The patients were divided into two groups: those operated on by day 3 (group 1: 116 patients) and those operated on after day 20 or not operated on (group 2: 34 patients). Severity of both subarachnoid hemorrhage on computed tomography scan and angiographic vasospasm were graded into 0-IV. Angiographic vasospasm was observed in 95% of group 1 and in 88% of group 2 patients. A significant difference could not be found between groups 1 and 2 in the angiographic vasospasm grades. The incidence of symptomatic vasospasm in group 1 was 18%, which was significantly lower than the 44% in group 2. In group 1 patients with subarachnoid hemorrhage grades II to III, the incidences of symptomatic vasospasm and low density area on computed tomography scan were 13% and 10%, respectively. Both of these rates were significantly lower than those in group 2, which were 50% and 36%, respectively. However, in patients with subarachnoid hemorrhage grade IV, no differences could be found between groups 1 and 2. There was a close correlation between the angiographic vasospasm grades and the incidence of symptomatic vasospasm in group 1. However, in group 1, no correlation could be observed between the site of ruptured aneurysms or the timing of operations and vasospasm. Although there is still a limit to the effect of early operation on cerebral vasospasm in patients with subarachnoid hemorrhage grade IV, symptomatic vasospasm after subarachnoid hemorrhage may be ameliorated by early operation in patients with subarachnoid hemorrhage grades II to III. PMID- 2326729 TI - Selective occlusion of blood supply to the anterior perforated substance of the dog: a highly reproducible stroke model. AB - We created a highly reproducible stroke model in dogs by the selective occlusion of middle and anterior cerebral artery branches that penetrate the anterior perforated substance and supply much of the basal forebrain. We also analyzed the anatomic organization of the arterial supply to this region in this animal. Perforators came from anterior communicating artery branches similar to the recurrent artery of Heubner in humans and from the middle cerebral artery at several sites distal to the bifurcation of the internal carotid artery. Although some animals had a single source of the perforating arteries, most had two or more. In 50% of our specimens, the anterior communicating artery was the dominant source of arterial supply, in 21% the middle cerebral artery was dominant, and in 24% neither source dominated. Occlusion of all microscopically visible perforators to the anterior perforated substance reliably resulted in infarction of the internal capsule (100%), caudate nucleus (91%-100%), putamen or globus pallidus (82%-91%), and anterior commissure (73%). Structures involved less frequently in infarctions include the external capsule, claustrum, anterior commissure, and septal nuclei. We believe this anatomic information is useful for understanding why previous focal ischemia lesions in the distribution of the middle cerebral artery in the dog have been highly variable as well as for planning and interpreting future studies in this species. The proposed model of focal ischemia may be of use for the study of stroke. PMID- 2326730 TI - Avulsion of choroid plexus during revision of ventricular shunting: its high incidence and predictive value on computed tomography scan. AB - Over a 2-year period, 5 of 10 patients with revision of ventricular shunting were complicated by intraventricular and/or intracerebral hemorrhage due to avulsion of the choroid plexus. Retrospective analysis of computed tomography scans prior to the revision disclosed the presence of an intraventricular or periventricular mass adjoining the ventricular catheter in four of the five patients. Histologic findings of the soft tissue at the tip of the removed catheter were compatible with the choroid plexus accompanied by granulation tissue. The risk factors useful for detecting the possible occurrence of this complication are discussed. PMID- 2326732 TI - Diagnosis and management of pyogenic vertebral osteomyelitis in adults. AB - Management of vertebral osteomyelitis remains controversial regarding optimum duration of antibiotic therapy and the role of surgery. Forty adults with vertebral osteomyelitis were reviewed. Staphylococcus aureus was the most common pathogen isolated. Disk space narrowing with end-plate erosion was the earliest finding, followed by progressive vertebral body destruction. Magnetic resonance imaging proved extremely valuable in detecting spinal cord compression in patients with neurologic deficit. Treatment should include at least 8 weeks of intravenous antibiotics combined with immobilization for pain reduction. Surgical intervention is indicated for all patients with neurologic deficit. Serial erythrocyte sedimentation rates are valuable for following response to therapy. The value of magnetic resonance imaging in diagnosis is emphasized. PMID- 2326731 TI - Leukocyte involvement in cerebral ischemia and reperfusion injury. AB - Leukocytes have been postulated to contribute to cerebral ischemia and reperfusion injury. The present study implies that leukocytes have a deleterious effect in the brain following ischemia. We compared the alteration of cortical electrical activity following transient, incomplete cerebral ischemia in control and leukopenic rats by monitoring somatosensory evoked potentials and electroencephalographic activity. There was complete cessation of electroencephalographic activity, and the cortical peak of the evoked potential was abolished during ischemia in the control animals. However, when the animals were rendered leukopenic, there was maintenance of electroencephalographic activity with reduced amplitude and preservation of the cortical peak of the evoked response during the ischemic period. This indicates that when the animals are made leukopenic, even under ischemic conditions, the neurophysiologic functioning is still maintained to a certain extent. PMID- 2326733 TI - Two pediatric cases with occlusions of the ipsilateral internal carotid and posterior cerebral arteries associated with moyamoya vessels: "unilateral" moyamoya disease. AB - Two pediatric cases of unilateral Moyamoya disease are reported. The clinical symptoms and the findings of electroencephalography, angiography, and positron emission tomography in these cases were quite the same as those in the cases with bilateral involvement, which is typical of this disease. In both cases angiography demonstrated unilateral occlusion not only of the internal carotid artery but also of the posterior cerebral artery together with so-called Moyamoya vessels on the same side. Although infectious diseases were mentioned in the patients' histories, no obvious basic diseases related to the cerebrovascular occlusion were detected. We consider that these cases with unilateral involvement suggest the presence of unilateral Moyamoya disease without progression onto the opposite side. PMID- 2326734 TI - Magnetic resonance imaging of spinal cord injury without radiologic abnormality. AB - A 3-year-old girl with spinal cord injury without radiologic abnormality (SCIWORA) is reported. Magnetic resonance imaging (MRI) showed an abnormal intensity of the spinal cord at the level of C7 to Th1 in the acute stage and severe atrophic change in the chronic stage. This is the first report of SCIWORA with positive diagnostic imaging. The mechanism of SCIWORA is discussed based on the positive MRI findings. PMID- 2326735 TI - Successful treatment of adult Arnold-Chiari malformation associated with basilar impression and syringomyelia by the transoral anterior approach. AB - A case of adult type I Arnold-Chiari malformation associated with basilar impression, syringomyelia, atlantoaxial dislocation, and occipitalization of the atlas is reported. Preoperative magnetic resonance imaging clearly revealed evidence of severe anterior compression of the cervicomedullary junction due to basilar impression and a sharp clivoaxial angle. Therefore, transoral anterior decompression and fusion were performed, resulting in an improvement of the patient's neurologic signs and symptoms. Postoperative magnetic resonance imaging showed an obvious reduction of the tonsillar herniation and syringomyelia, as well as an improvement of the cervicomedullary compression. PMID- 2326736 TI - Surgery and monitoring of traumatic intracerebral hematomas. PMID- 2326737 TI - [In vivo determination of tumor volume: what does a CT-based calculation mean in recurrences of rectal carcinoma?]. AB - The volumetric analysis of a tumour by CT is a reliable and clinically important method of examination which is rarely used. As for oncology, the importance of this method is based upon the determination of the stage of remission post therapeutically, especially in those cases which respond to therapy without a roentgenologic change in comparison to pretherapeutic findings. This applies in particular for the evaluation of CT images. In this study 115 CT examinations of 38 patients with recurrent rectal cancer were evaluated and the tumour remission was measured by an exact determination of the tumour volume before and after radiotherapy. The results were compared with the CT findings without volumetric analysis. A change of the tumour size up to 20% of the pretherapeutic volume which eludes from the visual perception can be revealed by a subtle CT-assisted volumetric analysis. Formulas for calculation of the volume or the data concerning length, width and depth of a mass prove to be insufficient or incorrect. Therefore the correct evaluation of a tumour regression or progression should be done more often by CT-assisted volumetric analysis. PMID- 2326738 TI - Neutron dosimetry intercomparisons between National Accelerator Centre, Universite Catholique de Louvain and Clatterbridge Hospital. AB - Neutron dosimetry intercomparison studies have been undertaken at three neutron therapy facilities which have similar beam characteristics; viz. National Accelerator Centre, South Africa [p(66 MeV)+Be], Universite Catholique de Louvain, Belgium, [p(65 MeV)+Be] and MRC Cyclotron Unit, Clatterbridge Hospital, U. K. [p(62 MeV)+Be]. The procedures followed at all centres were the same: tissue equivalent (TE) ionization chambers were first calibrated in 60Co beams and then exposed under various conditions in the respective neutron therapy beams. Measurements were made with the chambers flushed with TE gas or filled with static air. The neutron beam measurements differed by a maximum of 2.4%, whereas if only one particular type of ionization chamber is considered the spread in values is reduced to +/- 0.5%. The TE gas/air response ratios are consistent with calculated values. The results obtained are highly satisfactory and confirm that the dosimetry procedures adopted by the participating institutes conform to international standards. PMID- 2326739 TI - Alternative irregular field collimation for fast neutron therapy. AB - The neutron therapy program at the King Faisal Specialist Hospital and Research Centre was resumed in the spring of 1987. Due to the limited number of standard treatment cones, some form of beam modification was necessary. Originally we chose a cast iron blocking system, as adopted by other neutron treatment centers. For several reasons we found this arrangement to be generally unsatisfactory and inconvenient. We therefore, developed an alternative collimation system which resolved our earlier difficulties. PMID- 2326740 TI - [A rapid radiotherapy planning program in intracavitary afterloading therapy]. AB - A recently developed program for the irradiation planning of intracavitary afterloading applications in the treatment of gynecological diseases is presented. On the basis of measured data, a rapid algorithm for calculating the dose within the field near to ray emitters is introduced which avoids any uncertainties as to the greatest activity and the dose rate constant. Distance- and direction-dependent corrections of the inverse square law are performed by means of polynomials easy to calculate or by tables. The structure and performance of the program are described. Some examples are given in order to illustrate the possible applications of the irradiation planning program. PMID- 2326741 TI - Visual rehabilitation of aphakic children. PMID- 2326742 TI - Acute homonymous field loss: really a diagnostic dilemma. AB - A young woman developed the sudden onset of a congruous right lower quadratic visual field defect two weeks prior to examination. The remainder of her history and physical examination were noncontributory. Discussion revolves around the differential diagnosis of retro chiasmal field defects in young individuals. An MRI scan was most compatible with the diagnosis of disseminated sclerosis. PMID- 2326743 TI - Masseter muscle performance. Significance of structure and metabolism. A morphological and experimental study. AB - The aim of this thesis was to characterize structural factors in masticatory systems relevant to functional evaluations and to elucidate the effect on energy metabolism of electrically induced jaw muscle fatigue. An omnivorous masticatory system (the domestic pig) was compared morphologically with a carnivorous (the dog). Porcine masseter muscles were evaluated by ATP-ase histochemistry as well as with NADH-dehydrogenase and PAS-staining. Contractional characteristics were obtained from the porcine and canine masseters by electrical stimulation. The 133Xenon clearance technique and a flexible oxygen electrode were employed. A bite-force transducer was used. The porcine craniomandibular joint (CMJ) lacked a pronounced mandibular fossa and had anteriorly orientated cylindrical condyles. The dog CMJ comprised a cylindrical condyle orientated at right angles to the satittal plane and medially inclined. The pronounced mandibular fossa and marked tubercle, together with a well-developed retro-articular process, surrounded the condyle. The masticatory muscles were the same in the two species, except for the pig's zygomatico-mandibular muscle. The ATP-ase technique failed to reveal type II:B-fibres in the porcine masseter after acid and alkaline preincubation and it was not possible to separate fibre types by glycogen-staining and NADH dehydrogenase histochemistry. These findings diverged from the pig soleus histochemical profile (type II:B-fibres 60%). The quantitative evaluation revealed 75% type II:A-fibres in the porcine masseter. No statistically significant difference was found between the various fibre-type diameters in the porcine masseter. The mean fibre Type diameter was larger in the porcine masseter than in the soleus muscle. Type II-fibres were more frequently found on the edge of the fascicles. The bite force recordings showed that the porcine masseter was capable of long endurance performance, in contrast to the easily fatigued canine masseter. Significant reductions of intramuscular substrates and a considerable lactate accumulation were observed. The NADH/NAD-shuttle was oppositely directed in the two species. The blood-flow recordings revealed a marked blood-flow impairment during contraction, followed by a prominent post-exercise hyperaemia. The pO2 recordings were closely related in time as well as in mangnitude to the blood flow. It is thus concluded, based on morphological observations, that the porcine masticatory system bears resemblance to the human situation. In the canine masseter muscle, a relationship was found between metabolism and mechanical bite-force output. This correlation was not so evident in the porcine masseter. Induced jaw muscle hyperactivity may lead to a reduced energy and redox state and, as a late consequence, to fatigue. PMID- 2326744 TI - [Family work: cooperation with families of young schizophrenics--a new dimension in psychiatric nursing]. PMID- 2326745 TI - [Exciting field of work. Practical work among immigrants and refugees]. PMID- 2326746 TI - [Family work: families' coping strategies]. PMID- 2326747 TI - [National groups--a better name?. Interview by Kjell Arne Bakke]. PMID- 2326748 TI - [Midwife's working day]. PMID- 2326749 TI - [Current Oslo Report: illness absenteeism and burden in nursing homes and health visiting]. PMID- 2326750 TI - [International trends: nurses in readiness for the UN]. PMID- 2326751 TI - Effects of phorone and/or buthionine sulfoximine on teratogenicity of 5 fluorouracil in mice. AB - Embryotoxicity and teratogenicity of 5-fluorouracil (5-FU) and modulation of its effect by the depletors of glutathione (GSH) were evaluated in mice. Pregnant ICR mice were intraperitoneally (i.p.) injected with 25 mg/kg of 5-FU on day 11 of gestation (vaginal plug = day 0). Mice were pretreated i.p. with 250 mg/kg of phorone, a GSH depleting agent and/or 200 mg/kg of buthionine sulfoximine (BSO, an inhibitor of GSH biosynthesis) 4 hours before dosing with 5-FU. Dams were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations. Pretreatment with phorone or BSO decreased fetal weight and increased the frequency and severity of oligodactyly induced by 5-FU, as well as the reduction of maternal GSH levels. Combined use of 125 mg/kg phorone and 100 mg/kg BSO i.p. augmented growth retardation induced with 5-FU. Cotreatment with exogenous GSH, at a dose of 300 mg/kg injected intravenously, could not suppress the augmentative effects of phorone and/or BSO on 5-FU teratogenicity under these experimental conditions. These results indicate that the level of endogenous GSH is one of the factors which significantly affects teratogenicity of 5-FU. PMID- 2326752 TI - Effects of retinoic acid on the distribution of glycoconjugates during mouse tail bud development. AB - Retinoic acid (RA), a potent teratogen of caudal axial development in rodents, has been shown to alter glycoconjugates in a variety of embryonic tissues and teratocarcinomas. In this study, we examined its effects on the expression of cell surface and extracellular matrix glycoconjugates during tail bud development in mouse embryos by using lectin histochemistry. The lectins WGA, sWGA, and PNA showed striking differences in binding between RA-exposed and control embryos. Computer-assisted densitometry revealed a significant increase in binding of all three lectins to the extracellular material of the luminal and abluminal borders of the secondary neural tube and surrounding the notochord in RA-exposed embryos. RA-treated embryos also showed an increased binding affinity for the lectins sWGA and PNA to the cells of the notochord, while WGA showed increased binding to the neuroepithelial cells of the secondary neural tube. The results suggest that RA affects the expression of lectin binding sites during the early development of RA induced caudal axial defects. PMID- 2326753 TI - Ethanol treatment induces a delayed segmentation anomaly in the chick embryo. AB - A repeatable somite anomaly is described that results from the incubation of cultured chick embryos in the presence of ethanol. The anomaly comprises a misalignment of approximately five consecutive pairs of somites such that one of each pair is displaced cranially by up to one-half a somite length. The appearance of the malformation is delayed by approximately six somite pairs after the beginning of treatment. These characteristics were shared by embryos treated at the stage of gastrulation (no somites yet present) up to embryos possessing ten pairs of somites at treatment time. The deleterious effect did not appear to result from a disruption in the mechanics of the segmentation process itself, since isolated segmental plates were able to form normal intersomitic clefts in the presence of ethanol. Similarly, there were apparently no alterations in the compaction process that occurs at the cranial end of the segmental plate, since both the contractile and adhesive components were unaffected, as judged by the distributions of actin and fibronectin. The potential mechanisms of the anomaly are discussed with reference to similar segmental defects produced by heat shock. In view of earlier results indicating that cells in the primitive streak at gastrulation are sensitive to the presence of ethanol, it is proposed that this somite anomaly is due to a disruption in the contribution of these mesoderm cells to the segmental plate. PMID- 2326754 TI - Processes involved in retinoic acid production of small embryonic palatal shelves and limb defects. AB - All-trans-retinoic acid (RA) is teratogenic to the embryonic mouse, producing malformations in many developing systems, including the limb bud and palate. High incidences of limb defects and cleft palate are induced at doses which are not maternally toxic and do not increase resorptions. Exposure to RA on gestational day (GD) 10 results in small palatal shelves, which fail to make contact on GD 14. The formation of small shelves could be a consequence of increased cell death, reduced proliferation, a combination of these effects, or some other effect such as inhibition of extracellular matrix production. After exposure to 100 mg RA/kg on GD 10, proliferation in mesenchymal cells of the palatal shelves was not reduced from GD 12 to GD 14 and the levels of cell death in control and treated shelves did not differ when observed by light and electron microscopy. The present study examines the effects of RA on cell death and proliferation from GDs 10-12 and compares the effects in palatal shelves and limb buds. Embryonic mice were exposed to RA suspended in corn oil (100 mg/kg on GD 10), a dose that was teratogenic but not maternally toxic or embryolethal. Embryos were collected at 4, 12, 24, 36, or 48 hr postexposure, and tissues which form the palate or limb were dissected from the embryos, stained by a modified Feulgen procedure, and whole mounted on slides. Mitotic index (MI) and percentage dead cells were determined for mesenchymal cells of the first visceral arch, maxillary process, or palatal shelf (depending on stage of development) and forelimb buds. In the palatal tissues from GD 10 to GD 12, RA did not significantly alter MI and percentage dead cells was significantly increased only at 4 hr postexposure. Some whole embryos were prepared for scanning electron microscopy (SEM). At 48 hr (GD 12) a reduction in the size of the shelves was not apparent on SEM. In the limb buds, RA did not increase percentage dead cells, but MI was significantly decreased. A decreasing rate of proliferation was detected in control facial tissues as development progressed, and this agrees with findings in rat and chick. Thus it appears that mesenchymal cell death and reduced proliferation are not responsible for the small palatal shelves seen on GD 14. RA did not increase cell death but inhibited proliferation in the limb bud, and this effect may contribute to the retarded development and malformations occurring in the limb. PMID- 2326755 TI - Teratogenicity of carbamazepine in rats. AB - The teratogenicity of carbamazepine (CBZ) was investigated in Sprague-Dawley CD rats at doses of 0, 200, 400, and 600 mg/kg administered by gavage in corn oil on days 7-18 of gestation in a dosage volume of 2 ml/kg. The CBZ-600 dose was maternally toxic in that dams in this group weighed 30.6% less than controls by E20. This group had significantly increased resorptions, reduced live fetal weight (51.6% less than controls), and increased skeletal and visceral abnormalities. The CBZ-400 dose also significantly reduced maternal weight gain during gestation to 26.6% less than controls by E20. No significant increase in resorptions occurred in this group; live fetuses weighted 42.9% less than controls and showed an increase in visceral, but not skeletal, abnormalities. The CBZ-200 dose did not significantly affect maternal weight gain or increase resorptions or fetal abnormalities but did reduce fetal body weight (20.3% less than controls). Maternal serum total CBZ concentrations 1 hr after the final dose were 22.9, 27.9, and 34.4 micrograms/ml for the 200, 400, and 600 mg/kg groups, respectively. These levels were little changed 6 h post-treatment. CBZ was 65-70% serum protein bound across dose groups. Human therapeutic levels of CBZ are 4-12 micrograms/ml and the drug is typically 80% serum protein bound. This suggests that abnormalities in rats occur at concentrations well above the human therapeutic range. However, a no-effect level was not found for fetal body weight. Further experiments will be required to determine how much lower doses will need to be in order to find a no-effect level for fetal body weight. Nevertheless, the present data suggest that CBZ is not potent at inducing malformations in rats. PMID- 2326756 TI - Maternal diabetes and cardiovascular malformations: predominance of double outlet right ventricle and truncus arteriosus. AB - Most studies on the relationship of maternal diabetes to cardiovascular malformations (CVM) have been prospective investigations of pregnancy outcome and therefore could not identify associations with rare cardiac lesions. The results of a retrospective study shed new light on the risks of specific cardiac defects in diabetic pregnancies. The Baltimore-Washington Infant Study, a population based case-control investigation of CVM, provides information on maternal diabetes reported in personal interviews. Among 2259 mothers of cases, 35 (1.5%) reported diabetes present before pregnancy (called "overt") and 95 (4.2%) reported diabetes only during pregnancy (called "gestational"). Among 2,801 mothers of controls, 14 (0.5%) had overt diabetes and 83 (3.0%) had gestational diabetes. Malformation-specific risks were expressed as odds ratios (OR) with 99.5% confidence intervals (CI). The strongest associations with overt maternal diabetes were found with double outlet right ventricle (OR 21.33; 99.5% CI 3.34, 136.26), and truncus arteriosus (OR 12.81; 99.5% CI 1.43, 114.64). No significant diagnosis-specific associations were found with gestational diabetes. Non-cardiac malformations were present in 23% of infants with CVM whose mothers had overt diabetes and in 26% of infants with CVM whose mother had gestational diabetes, in 32% of infants with CVM whose mothers did not have diabetes, and in 4% of controls. Double outlet right ventricle and truncus arteriosus are malformations dependent upon neural-crest-cell-derived ectomesenchymal tissues; these are precisely the conotruncal abnormalities that result from experimental ablation of the neural crest in chick embryos. The association with diabetes suggests a further etiologic link between these two lesions. PMID- 2326757 TI - Umbilical cord growth in human and rat fetuses: evidence against the "stretch hypothesis". AB - A total of 103 human fetuses between the 7th and 30th week of gestation were obtained from induced abortion (40 fetuses were normal and 63 were abnormal), and the umbilical cord length (UCL) was measured. The UCL increased almost linearly with gestational age among normal fetuses, contrary to the commonly held tenet that the UCL increases exponentially during the second trimester. When UCLs from the 63 abnormal fetuses were compared with those of normal fetuses, 15 fetuses were found to have short UCL and 10 fetuses to have long UCL. Among the 15 fetuses with short UCL, 6 had early amnion rupture syndrome. An unexpected finding among the 10 with long UCL was that 8 of them had oligohydramnios. It has been suggested that the UCL increases in response to tensile forces placed upon it ("stretch hypothesis"); however, our results are inconsistent with this hypothesis because fetuses with oligohydramnios should be less active and their umbilical cords be subject to less stress. In a separate experiment, we studied the normal development of the UCL in rat fetuses and observed an almost linear increase during the whole gestation similar to that seen in humans. This finding is also inconsistent with the "stretch hypothesis" because amniotic fluid volume decreases significantly from day 19 of gestation to term in rats. PMID- 2326758 TI - Examination of a rodent limb bud micromass assay as a prescreen for developmental toxicity. AB - The mouse limb bud micromass assay is one of many short-term tests proposed as preliminary screens for potential developmental toxicity. Previous efforts to validate this assay have used too few "nonteratogens." The purpose of this study was to examine additional compounds, most of which, based on the literature, were perceived to have low potential for developmental toxicity in vivo. In addition, a method of data analysis was sought that would identify selective developmental toxins in the micromass assay, i.e., those that are effective at dosages not maternally toxic. The concentration of each of 23 compounds that produced a 50% inhibition (IC50) of radiolabeled thymidine (T) and sulfate (S) incorporation was determined and used to calculate a T/S ratio. The T/S ratio may be a useful measure of developmental hazard, since T incorporation measures toxicity toward a general cell function (DNA synthesis) and S incorporation measures mainly toxicity toward a developmentally specific cell activity (chondroitin sulfate synthesis). All compounds tested produced T/S ratios of less than 2.0. Since 22 of these 23 compounds are classified as "nonteratogens" or nonselective developmental toxins in vivo, a low T/S ratio in this in vitro assay system may be capable of discriminating potential for developmental hazard in vivo. PMID- 2326759 TI - The Teratology Society, thirtieth annual meeting. June 8-12, 1990, Victoria, BC, Canada. Program, abstracts. PMID- 2326760 TI - Neurobehavioral Teratology Society, fourteenth annual meeting. June 7-10, 1990, Victoria, British Columbia, Canada. Program and abstracts. PMID- 2326761 TI - The number of alleles in multigene families. AB - The probability distribution and moments of the number of alleles present in a sample of homologous chromosomes are studied. It is assumed that there are multiple copies of the gene on each chromosome. When there are only two copies per chromosome or when there are only two or three chromosomes, it is possible to use analytic methods to tackle the problem. Otherwise, a simulation method is suggested. PMID- 2326762 TI - Levels of multiallelic overdominance fitness, heterozygote excess and heterozygote deficiency. AB - Concepts and results on selection balance in multiallelic systems are described. These include a multidimensional concept of heterozygote excess and heterozygote deficiency, a hierarchy of means of assessment of heterozygote advantage, comparisons and contrasts of allelic versus gametic polymorphic states, and conditions defining stable equilibria of complementary gametic sets. The concepts are illustrated in the context of viability selection and behavioral models of kin selection and for two major categories of multilocus selection regimes. PMID- 2326763 TI - Some models of neutral evolution, compensatory evolution, and the shifting balance process. PMID- 2326764 TI - How gene families evolve. AB - Theories and facts of gene family evolution are reviewed. Concerted evolution is commonly observed for gene families which originated a long time ago, however there are many different types of multigene families, from uniform to diverse. The rate of homogenization by unequal crossing-over, gene conversion, etc. has been evolutionarily adjusted for each gene family. When new functions are needed by organisms, gene families may evolve into superfamilies, in which no further concerted evolution takes place, and each member of the family may acquire an indispensable function. The homeobox-containing gene family is a most exciting example of such superfamily. PMID- 2326765 TI - The variance of sample heterozygosity. AB - The variance of sample heterozygosity, averaged over several loci, is studied in a variety of situations. The variance depends on the sampling implicit in the mating system as well as on that explicit in the loci scored and individuals sampled. There are also effects of allelic distributions over loci and of linkage or linkage disequilibrium between pairs of loci. Results are obtained for populations in drift and mutation balance, for infinite populations undergoing mixed self and random mating, and for finite monoecious populations with or without selfing. For unlinked loci in drift/mutation balance, variances appear to be lessened more by increasing the number of loci scored than by increasing the number of individuals sampled. For infinite populations under the mixed self and random mating system, however, the reverse is true. Methods for estimating the variance of sample heterozygosity are discussed, with attention being paid to unbalanced data where not all loci are scored in all individuals. PMID- 2326766 TI - Long-term response to artificial selection with multiple alleles--study by simulations. AB - The effect of multiple alleles on long-term response to selection is examined by simulations using a pseudosampling technique to simulate the multidimensional diffusion process. The effects of alleles are independently drawn from a normal distribution and the initial frequencies of alleles are assumed either to be equal or to be drawn from a neutral equilibrium population. With these two initial gene frequency distributions we examined various properties of the selection response process for the effects of number of alleles and selection intensity. For neutral initial frequencies the effects of multiple alleles compared with two alleles are minor on the ratio of final to initial response (E(R infinity/E(R1)) and the half life of response (t0.5), but are significant on the variance of response. Under certain conditions the variance of the selection limit can even increase as selection gets stronger. For equal initial frequencies the effects of multiple alleles are, however, minor on the ratio of the variance of the selection limit to the initial genetic variance, but E(R infinity/E(R1) and t0.5 increase as the number of alleles increases. The results show that for certain statistics the effects of multiple alleles can be minimized by an appropriate transformation of parameters for given initial gene frequencies, but the effects cannot, in general, be removed by any single transformation or reparameterization of parameters. PMID- 2326767 TI - Spatial subdivision of populations and estimates of genetic variation. AB - Measures of variation in space are strongly affected by correlations between subdivisions used for sampling. Here we consider variation in gene frequencies across populations. Usually the variance of gene frequencies is standardized by dividing it by the mean gene frequency times one minus the mean (FST). Under the model of isolation by distance (usually called the "stepping stone" model), at the stationary state the correlation between the gene frequencies of two populations falls exponentially with the geographic distance between them. Using this model, we derive formulas for variances of blocks of populations of different sizes in one- and two-dimensional space and suggest that the theoretical results may be useful for understanding real observations, some examples of which are presented. We demonstrate how FST increases with the degree of subdivision among populations. We also show the effect of gaps between the sampled populations. Our results are valid, however, for traits other than gene frequencies, as long as their correlation with geographic distance falls exponentially. In the extension to 2-dimensional spaces, we present in closed form the distributions of distances between nodes of a lattice or of two lattices. These distributions might have applications in ecology. PMID- 2326768 TI - Simplified models for viability selection at multiple loci. PMID- 2326769 TI - The molecular nature of allelic diversity for two models of balancing selection. AB - This paper provides a theoretical description of the distribution of the number of mutations that separate alleles that are held in a population by balancing selection. Two models of nucleotide site epistasis are described: parity models and additive site models. Parity models are shown to result in a more uniform distribution of mutations across alleles than the neutral model, while additive sites models show a more extreme distribution. The analytic approach uses strong selection, weak-mutation approximations to constant-fitness and random environment diffusion models. PMID- 2326770 TI - Comparison of methods for detecting soluble fibrin in plasma. An in vitro study. AB - The ability of the COA-SET Fibrin monomer (COA-SET FM) test to detect soluble fibrin was evaluated by comparing the results of the COA-SET FM test with fibrinopeptide A (FPA) determinations following thrombin incubation of plasma or whole blood. In addition, two semiquantitative tests (erythrocytes-agglutination test (FM-test) and ethanol gelation test (EGT] were included in the study. Under the experimental conditions used, the COA-SET FM test proved less sensitive than the FPA-assay. There was a strong correlation between the results obtained by the two tests (r = 0.86, p = 0.0001). When solely regarding low levels of soluble fibrin, however, the correlation was weaker (r = 0.59, p = 0.0003). The FM-test was less sensitive than the COA-SET FM test, but more sensitive than EGT at normal and low fibrinogen concentrations. At high fibrinogen concentrations, however, EGT proved more sensitive than the FM-test. Knowing that 1-2 moles of FPA are released per mole of fibrin monomers formed, a discrepancy was observed between the FPA concentrations and the fibrin monomer concentrations as determined by the COA-SET FM test, the FPA levels being 2-25 times higher than the fibrin monomer levels. The discrepancy was greatest at incipient fibrinogen fibrin transformation and at high plasma fibrinogen levels. This may suggest that fibrinogen in some way interfered with the stimulating effect of fibrin on the t PA catalyzed activation of plasminogen, the principle upon which the COA-SET FM test is based.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326771 TI - Protective effect of Y-20811, a long-lasting thromboxane synthetase inhibitor, on endotoxin shock in rabbits. AB - The effect of sodium 4-[alpha-hydroxy-5-(imidazolyl)-2-methylbenzyl]-3,5-dimethyl benzoate dihydrate (Y-20811), a selective thromboxane (TX) synthetase inhibitor, on endotoxin shock was investigated in comparison with aspirin. The drugs were orally administered to rabbits at 24 and 1 hour before injection of endotoxin (5 mg/kg, i.v.). Y-20811 (1 mg/kg) promoted the recovery of decreased platelet counts, and inhibited hypotension induced by endotoxin. It also inhibited the increase in plasma TXB2 and 6-keto PGF1 alpha. Aspirin at 30 mg/kg, inhibited hypotension and the increase in both plasma TXB2 and 6-keto PGF1 alpha levels, but it failed to inhibit the decrease in platelet counts. In the control group, all rabbits died within 180 min after endotoxin injection, while Y-20811 completely protected animals against death at a dose of 0.3 mg/kg. Aspirin also protected animals against death at a dose of 30 mg/kg, which was, however, about one hundredth potent of Y-20811. These results indicate that Y-20811 is useful in treating endotoxin shock. PMID- 2326772 TI - The prothrombin activation peptide regulates synthesis of the vitamin K-dependent proteins in the rabbit. AB - The turnover of 125I-bovine prothrombin fragment 1 was studied in the rabbit. The t1/2 of the peptide in the intravascular compartment was 11.5 hours and this compartment accounted for between 7.9 and 14.4% of the injected radioactivity. The rest of the radioactivity was distributed between two compartments in the extravascular space. The injection of the peptide (10 mg/rabbit) was associated with a transient increase in the plasma concentration of prothrombin and of factor X, with maximum concentration of prothrombin between 40 and 66 hours from the injection and between 26 and 40 hours for factor X. It is concluded that the injection of fragment 1 in the rabbit induced a transient increase in the synthesis of the vitamin K-dependent proteins that is compensated for by an increased absolute catabolic rate. It is suggested that the prothrombin activation peptide serves as regulatory message which induces the subsequent restoration of the appropriate concentration of the vitamin K-dependent proteins. PMID- 2326773 TI - Platelet activating factor and sheep platelets: a sensitive new bioassay. AB - The in vitro response of sheep platelets to platelet activating factor (PAF) was investigated. Sheep platelet-rich plasma aggregated in response to PAF with an EC50 of 10 nM. Platelets isolated via arabinogalactan density gradient centrifugation displayed an EC50 of 50 pM with a threshold response at 0.1 pM. PAF-induced release of 14C-serotonin from isolated sheep platelets was comparable with an EC50 of 50 pM and threshold release at 10 fM. PAF-induced aggregation was specific in that it could be blocked by the competitive receptor antagonists Alprazolam (Upjohn, IC50 = 40 microM), L-652,731 (MSD, IC50 = 6 microM), and WEB 2086 (Boehringer Ingelheim, IC50 = 0.8 microM). At micromolar concentrations, WEB 2086 did not inhibit ADP- or thrombin-induced aggregation nor thrombin-induced serotonin release. However, at higher concentrations of WEB 2086 some inhibition of thrombin-induced platelet aggregation and release was observed. Subsequent experiments demonstrated that high concentrations of WEB 2086 can inhibit thrombin-induced clotting (Ki = 866 microM) and cleavage of the chromogenic substrate Spectrozyme-TH (Ki = 842 microM). In summary, the response of isolated sheep platelets to PAF was specifically inhibitable and was 10 to 100 times more sensitive than washed rabbit platelets, the most popular bioassay currently in use. PMID- 2326774 TI - Dose responses in platelet fatty acid composition, aggregation and prostanoid metabolism during moderate freshwater fish diet. AB - The dose responses in platelet fatty acid composition, aggregation and thromboxane production and in plasma prostacyclin level during moderate freshwater fish diet was studied in healthy male students (n = 100). There were four fish diet groups eating 0.9, 1.5, 2.3 or 3.8 fish-containing meals per week for 12 weeks. The meals provided about 0.25, 0.5, 0.6 or 1.1 g n-3 fatty acids per day, respectively. The increase of n-3 at the expense of n-6 fatty acids in total platelet lipids took place already with 1.5 weekly fish meals (0.5 g n-3 fatty acids/d). Most of the observed changes in platelet fatty acids were seen already after 5 weeks. ADP-and collagen-induced platelet aggregation was measured from controls and 1.5 and 3.8 fish meals per week groups. The maximum platelet aggregation values of the group with the highest fish intake were significantly lower than in the controls at the end of dietary period. A tendency towards reduced platelet aggregability was observed also in the group eating 1.5 fish meals per weeks. Thromboxane B2 and 6-keto-PGF1 alpha were determined from controls and two groups with highest fish intake. The highest intake was needed to decrease the thromboxane B2 production of clotted blood and the plasma 6-keto PGF1 alpha concentration. A positive correlation between ADP-induced aggregation and thromboxane B2 production was found. These results show that platelet characteristics can already be modified with a very moderate freshwater fish intake. PMID- 2326775 TI - Hereditary antithrombin III deficiency with a superior sagittal sinus thrombosis: evidence for a possible mutation starting in the mother of the propositus. AB - A patient with a superior sagittal sinus thrombosis (SSST) which occurred during the postpartum period is reported. Coagulation studies revealed persistently decreased antithrombin III (AT III) activity. Studies of AT III activity in her family revealed a hereditary AT III deficiency. Since AT III activity was normal in the grandparents of the propositus, the disorder in this family appears to be due to a spontaneous mutation occurring in the mother of the propositus. PMID- 2326776 TI - Local prevention of thrombosis in animal arteries by means of magnetic targeting of aspirin-loaded red cells. AB - Thrombosis was induced in 18 dog and 16 rabbit arteries by surgically inverting a vascular wall flap into its lumen. A completely occluding red thrombus was formed inside the vessel 4 to 5 hours later in 80% of cases. SmCo5 magnet was secured externally to one of the arteries. The constant magnetic field produced by the magnet had no influence on the clot formation. Autologous red cells loaded with ferromagnetic colloid compound and aspirin were administered intravenously and completely aborted arteriothrombosis on magnet-supplied side with no deterioratory effect on clot formation in the control artery. PMID- 2326777 TI - Quantitative comparison of recombinant hirudin's antithrombotic and anticoagulant activities with those of heparin. PMID- 2326778 TI - Low doses of activated protein C delay arterial thrombosis in rats. PMID- 2326779 TI - Rapid diagnosis of von Willebrand's disease using ELISA technology. PMID- 2326780 TI - Erythrocyte deformability in patients with an ischemic pathology. PMID- 2326782 TI - [A safe system of urine collection in cows]. AB - The usual method of sampling urine in cows involves the risk of ingestion of micro-organisms, particularly Leptospira hardjo. A simple system is described, in which this risk is reduced to a minimum. This system can also be used in sampling urine in mares. PMID- 2326781 TI - [Serological study of the presence of Actinobacillus pleuropneumoniae antibodies serotype 2 and 9 on pig-breeding farms in the provinces of North Brabant and Overijssel (The Netherlands)]. AB - Serological studies for the presence of CFT antibodies to Actinobacillus pleuropneumoniae, both to serotype 2 and serotype 9, were done in twenty-five sows on each of thirty pig-breeding farms in the provinces of North Brabant and Overijssel. Antibodies to serotype 2 and/or serotype 9 were detected in one or several sows on forty-two out of sixty farms. Similar findings were recorded on eighteen and twenty-four farms respectively in the provinces of Overijssel and North Brabant; the number of herds showing positive reactions to serotype 2 was sixteen and twenty-three in these provinces respectively, that showing positive reactions to serotype 9 being six and five respectively. An average proportion of nineteen per cent of the samples taken on the farms having serologically positive animals was positive for serotype 2, and twelve per cent for serotype 9. Only one of the twenty-five animals on twelve farms was found to be positive; serotype 2 was present in ten cases and serotype 9 in two cases. A marked effect of the size of the herds on the serological status of the farms was not observed in the present studies. This was also true of the purchasing policy; there was no difference between farms which had no longer purchased any breeding pigs for an average period of seventeen years and for one year respectively. Clinical symptoms of an infection due to Actinobacillus pleuropneumoniae were only reported as occurring on two farms having serologically positive animals. PMID- 2326783 TI - [Empirical study of the market orientation of veterinarians in The Netherlands]. AB - Linked to the theoretical framework of marketing in the veterinary practice, as explained in Schuurmans and Smidts (1) pp. 1-10 and Schuurmans and Smidts (2), an empirical research project has been undertaken. This research gives insight into the extent to which practices base their services on a marketing orientation. By means of telephone inquiries among a sample of 166 veterinarians, this was investigated. The research shows that veterinarians think more in a product oriented way than in a market-oriented way, and they do not use all the opportunities a marketing orientation could bring to their services. This expresses itself, among others by not using market segmentation, by the inadequate use of the marketing mix elements communication and distribution, and by the fact that the opportunities of the marketing information system are hardly applied. By means of further research in individual practices it might be possible to give concrete advise fit for that practice. Research among the clients of the veterinarians might, beside many other kinds of research, also give valuable insights. PMID- 2326784 TI - [Rachitis in yearlings permanently housed inside]. PMID- 2326786 TI - [Legislation concerning the Practice of Veterinary Medicine as accepted by the First Chamber]. PMID- 2326785 TI - [Veterinary Chief Inspection of Public Health. Integrated approach to Salmonella problems in poultry]. PMID- 2326787 TI - International Veterinary Congress 1990. Amsterdam, April 20-22, 1990. Abstracts. PMID- 2326788 TI - Sequential changes in the nucleoli of human spermatogonia with special reference to rDNA location and transcription. AB - The nucleoli of human spermatogonia were studied using electron microscopy, silver staining, radioautography and in situ hybridization. In all types of A spermatogonia, nucleoli were consistently located at the periphery of the nucleus and contained a single fibrillar center associated with the nuclear envelope. In B spermatogonia, nucleoli were centrally located in the nuclei and showed several fibrillar centers or were found to disintegrate. Nucleolar morphology was found to be a good, though not an unequivocal indicator of spermatogonial type. The observed changes in nucleolar morphology reflect the differentiation of spermatogonia: the nucleolar disintegration seen in B spermatogonia corresponds to a pre-leptotene cessation of rDNA transcription. In radioautographs following 3H-uridine uptake, the label was consistently found over the dense fibrillar component, except in the B spermatogonia with disintegrating nucleoli, where no uptake could be detected. In situ hybridization demonstrated that the distribution of rDNA did not correspond to the site of the fibrillar center but to the dense fibrillar component. Compared with radioautographs, this finding clearly established that transcribed units of rDNA were located in the dense fibrillar component. Silver staining was strongly positive in fibrillar centers and in the dense fibrillar component. In Ap spermatogonia the silver deposit was often localized at the edge of the fibrillar threads. The relationships between silver-stained proteins and transcribed and nontranscribed portions of ribosomal genes are reevaluated. PMID- 2326789 TI - Ontogenetic development of the brain of the platyhelminth Fasciola hepatica. AB - During ontogenetic development in the definitive host, the cerebral ganglia of the parasitic flatworm Fasciola hepatica lose their cell rind integrity and develop specialized nerve processes. The organization and cytological features of the central nervous system were examined during three developmental stages in the parasitic life cycle of F. hepatica to determine when the changes occur. The cerebral ganglion cell bodies of migrating juvenile worms (5 days post-infection) are organized into a one-cell-thick rind that surrounds a central neuropile composed of small unmyelinated nerve processes (less than 3 microns in diameter). In young, sexually-immature adult worms (30 days post-infection), the cell bodies of the ganglia are no longer organized into a complete or tight cell rind around the ganglia. In addition, large diameter ('giant') unmyelinated nerve processes (greater than 12 microns) are found in the neuropile area. These giant nerve processes are also found in the transverse commissure and the longitudinal nerve cords. In mature adult worms (4-6 months post-infection), the rind of nerve cell bodies has completely disappeared and cell bodies are scattered around and within the neuropile. More than half of the volume of the mature adult neuropile is composed of giant nerve processes. The three developmental stages of the parasite that were used in this study differ significantly in their sizes, behaviours and microhabitat locations in the host. The results suggest that the organizational and morphological changes in the ganglia reflect selective adaptations to changes in the parasitic microenvironment. PMID- 2326790 TI - Degradation of metal-labeled collagen implants: ultrastructural and X-ray microanalysis. AB - Three different metal salts, silver nitrate, uranyl acetate and lead citrate, are mixed with a collagen gel to produce 3 metal/collagen sponges. These sponges were implanted subcutaneously in the rat and samples harvested after 5 days of implantation. TEM observation shows that sponges are degraded and digested by macrophages, polymorphonuclear cells (PMN) and fibroblasts. We have observed that the location of the precipitates differs according to the metal added to the collagen. Lead precipitates stay longer on the collagen mesh while silver precipitates, after 5 days, are soon digested and are found in phagosomes of macrophages. Uranium precipitates are digested with the collagen and uranium/collagen associated pictures are seen in phagolysosomes. Metal precipitates accumulated in phagolysosomes of macrophagic cells are recognized by X-ray microanalysis. The degradation process of implanted collagen is discussed. PMID- 2326791 TI - Chondroclasts in osteoneogenesis. AB - Allogenic, demineralized bone powder (DBP) was implanted into rat rectus abdominis muscle to induce osteoneogenesis. The main induction steps are invasion of the implant by host mesenchyme cells, differentiation of cartilage, invasion by blood capillaries or angiogenesis, differentiation of osteoblasts and bone marrow. The result is the formation of a cancellous ossicle. Giant polykarions appear in the implant after calcification of the cartilage matrix. As the DBP particles are not resorbed in the implant, these polykarions could either be foreign body giant cells brought about in reaction to foreign matrix or chondroclasts which resorb the cartilage. The results obtained by histological and histochemical methods (McNeals-von Kossa stain, tartrate resistant acid phosphatase reaction), as well as ultrastructural studies, lead to the conclusion that these large polynucleated cells are chondroclasts. PMID- 2326792 TI - [Corrosion anatomical and scanning electron microscopic studies of the blood vessels in the digital end organ of the hindlimb of cattle]. AB - By aid of modern corrosion anatomical methods the afferent and efferent blood vessels as well as the microvasculature of the corium of the pelvic limb digit were investigated. The longest papillae are to be found in the perioptic corium. In the coronary corium the length decreases from proximal to distal. In the caudal section of the digital cushion the papillae show a typical, regular wavy form, whorl formation is rare. PMID- 2326793 TI - [Fibrosarcoma of the zygomatic bone in a fallow deer. Illustrated report]. PMID- 2326794 TI - [Hair alterations in trichophytosis of roe deer--a differential diagnosis for hair parakeratosis]. AB - A rare case of mycosis (ringworm) in a female roedeer is described and compared with parakeratosis of hair. It seems that in game, parakeratosis--as a primary lesion--predisposes to mycosis. PMID- 2326795 TI - [The effect of feed preparation on the pharmacokinetics of peroral administration of chlortetracycline in weaned piglets]. AB - The influence of different modes of feeding on the bioavailability of orally administered chlortetracycline was studied in weaned pigs. The animals were divided into three groups receiving a dry, a moist or a soup diet, respectively. CTC was applied at a concentration of 6000 ppm and 2500 ppm to each diet and the oral dosage of CTC was 40 mg chlortetracycline/kg bodyweight. The results of the experiments show that the pharmacokinetics of orally applied chlortetracycline are significantly influenced by the mode of feeding. A significantly higher bioavailability was observed with soup feeding compared with moist or dry food. To achieve a therapeutic blood level of 0.5-1.5 micrograms chlortetracycline/ml blood, 20-30 mg chlortetracycline/kg bodyweight/12 h and 30-40 mg chlortetracycline/kg bodyweight/12 h should be applied to soup and dry or moist feed, respectively. PMID- 2326796 TI - [Esophagoscopy and gastroscopy in dogs and cats. Technics and indications]. AB - A report is presented of esophagoscopy and gastroscopy in cats and dogs using flexible endoscopes. Following consideration of the basic equipment, an account is given of patient preparation and anesthesia, topography, investigation technique and normal findings. Diagnostic potential, indications and risks involved are discussed. PMID- 2326797 TI - [Clinical case. Epistaxis in a dog]. PMID- 2326798 TI - [Spectrum of species and infection frequency of endoparasites in bitches and their puppies in south Germany]. AB - Toxocara canis, Toxascaris leonina, hookworms, Trichuris vulpis, Strongyloides, Hammondia heydorni, Sarcocystis spp., Isospora canis and Isospora ohioensis and/or Isospora burrowsi of at least 9 species were detected in 100 randomly selected dog families in Southern Germany. Examinations carried out 5 to 9 times at weekly intervals revealed a monoinfection in 37 litters, infection with two parasite species in 28 litters, with three species in 10 litters and with four species in 6 litters. During the investigation period, 29 of the examined litters did not excrete helminth eggs, and, of these, 19 also did not excrete oocysts/sporocysts. In order of decreasing frequency among the dog families, the excretion extent of the litters and their mothers was as follows: Toxocara canis 67% and 45%, Isospora ohioensis/burrowsi 36% and 24%, Sarcocystis spp. 12% and 19%, Isospora canis 16% and 8%, Hammondia heydorni 7% and 6%, hookworms 6% and 7% and Toxascaris leonina 3% and 8%, respectively. Trichuris vulpis and Strongyloides eggs were only detected in 6 and 3 of the bitches, respectively. PMID- 2326799 TI - [Changes in the behavior of dogs after castration]. AB - This study is based upon a written survey of keepers of neutered dogs about the behaviour of 209 male and 382 female dogs. The main findings are: Male dogs show behavioural changes after castration more often and more distinctly than female dogs after neutering. Behavioural problems in most cases are reduced or have even disappeared after neutering (male dogs 74%, female dogs 59%). At best, hypersexuality and connected problems are changed as expected. 49 of 80 aggressive male dogs and 25 of 47 female dogs are more gentle after neutering. 10 bitches appeared to be aggressive only after being neutered. Particularly feeding behaviour changes in 42% of the male dogs and 32% of the female dogs towards an increased intake of food, which also leads to an increase in body weight. This corresponds to decreasing activity, which is indicated by increasing time of rest (male dogs 36%, female dogs 18%) and decreasing motivation to move. Motivation for playing, watchfulness and perseverance change more seldomly and sometimes increase. The character of the neutered animals is predominantly described as "devoted, friendly and kind". Changes of behaviour following neutering depend on many influencing factors. Above all effective obedience training, but also the family situation of the owner, time factors, conditions of keeping and contact with other dogs have different impacts on the control of the individual behavioural problems. PMID- 2326800 TI - [Legal prerequisites for drug treatment of ornamental fish and other pets]. AB - German pharmaceutical law provides protection for humans and animals by the means of four important regulations. In the case of non-prescription drugs for use in exotic pets, ornamental fish, cage or aviary birds, racing pigeons, small rodents, reptiles and amphibians only one of these regulations is applicable. However, the local authority retains the right of inspection as with all drugs. PMID- 2326801 TI - [The effect of calcium glycerophosphate and Remodent on the dental enamel permeability in dogs with fluorosis]. AB - In 14 dogs aged 6 months with severe fluorosis, the authors studied the effects of intake of calcium glycerophosphate and local remodent application on 45Ca enamel incorporation and the depth of its penetration into the dental hard tissues. The treatment led to a substantial decrease in both enamel 45Ca accumulation and the depth of its penetration under severe fluorosis. Combined use of the drugs was more beneficial in terms of enamel 45Ca permeability. PMID- 2326802 TI - [Carbohydrate-energy metabolism of periodontal bony tissue in the artificial modelling of traumatic occlusion]. AB - Experiments with 40 dogs have demonstrated that overexercise of the maxillodental system for 30 days results in reduction of the bioenergy potential of the periodontal bone tissue of the overloaded teeth. When the traumatic overload was eliminated for the next 30 days, the functional parameters gradually recovered, but the biochemical characteristics of the regenerated bone did not fully normalize. PMID- 2326803 TI - [A low-frequency magnetic field and regeneration of bony tissue of the jaw: optimization of exposure parameters (experimental research)]. AB - The optimal parameters of exposure to low-frequency magnetic field were chosen in experiments with 132 rats, using a simplex method of the extreme exposure. These parameters are as follows: 22 mT induction, length of exposure 20 min, pulse regimen. Exposure in such conditions provides the most effective influence of magnetic field on the reparative osteogenesis and mineralization processes and on the subsequent organic restructuring of the bone at the site of the mandibular standard defect. PMID- 2326804 TI - [An evaluation of the reparative regeneration of maxillary defects based on neutron activation analysis data (experimental research)]. AB - The major mineral components and electrolytes (K, P, Mg, Na, Cl, Mn, Fe, Co, Zn, Br, Sr) of the maxillary lamellar bone tissue and of the reparative regenerate were examined over the course of healing of maxillary nasofrontal artificial defects of various sizes (5 X 20, 7 X 20, 10 X 20 mm) perforating the nasal cavity. Check-ups carried out in 3, 4, and 8 mos after surgery have shown no osteal joining of the maxillary defect. The level of ossification by the 8th month of the follow-up, as evidenced by the content of the major osteotropic elements, just a little surpasses 50-70% of the normal value. PMID- 2326805 TI - [A clinico-pharmacologic study of intraseptal spongiosa dental anesthesia with lidocaine and with/without adrenaline]. AB - Intraseptal anesthesia of the maxillary lateral incisor with a 2% lidocain solution with and without epinephrine was studied in 22 examinations of electric sensitivity of the teeth. Addition of epinephrine was conducive to an increase of the depth, frequency, length, and dissemination of pulpal anesthesia and to elimination of undesirable reactions. PMID- 2326806 TI - [A difference in the mechanisms of the development of periodontitis]. AB - The study based on immunological and epidemiological evaluation of large groups of population has revealed the factors responsible principally for periodontitis pattern. They are: 1) microbial and tissue sensitization, 2) immune defences, 3) disturbed microcirculation in periodontal tissues. In view of various causes underlying periodontitis it is advisable to take them into consideration when evaluating diagnostic data and deciding on indications for immunocorrective therapy. PMID- 2326807 TI - [Kemantan treatment of patients with recurrent aphthous stomatitis]. AB - The authors assess the therapeutic efficacy of kemantan, an immunomodulator, used in the treatment of 30 patients with severe stubborn recurrent aphthous stomatitis (RAS). The blood immunological and biochemical characteristics were checked up over the course of treatment. Clinical and laboratory studies have shown that this immunocorrective agent is sufficiently effective for fibrous and cicatrizing RAS running a permanent course: the periods of the pathologic elements epithelialization are shortened, the permanent course of the condition is interrupted and the remissions are prolonged; clinical cure has been achieved in a number of cases. Kemantan is indicated for RAS patients only in cases with immunologic insufficiency, with immunologic responses monitored over the course of the treatment. PMID- 2326808 TI - [Liquid-crystal thermography in the diagnosis and assessment of treatment efficacy in patients with chronic lymphedema of the lips]. AB - Thermographic examination of 80 patients with chronic labial lymphedema (CLL) in various stages of the condition has revealed a clear-cut correlation between the process stage and thermal topography manifestations. This helped plan a differentiated approach to the choice of the treatment strategy in various CLL phases. Changed thermography data in the course of treatment evidence the possibility of applying this method to the assessment of the treatment efficacy in CLL. PMID- 2326809 TI - [A method for treating acute serous lymphadenitis by the action of novocaine block of the cervical autonomic ganglia]. AB - Thirty-five patients with acute inflammations of the soft tissues were treated with procain blockages of the cervical sympathetic ganglia. This treatment modality has helped cut down the patients' hospitalization period by 3-4 days and did not involve therapy with other drugs, this being an important factor for patients with antibacterial drug allergies, contributing to improvement of the efficacy of the suggested method. PMID- 2326810 TI - [Changes of the functional indices of the liver in patients with phlegmons of the maxillofacial area based on gamma scintigraphic data]. AB - Hepatic functional activity was studied. Liver was considerably enlarged and its functional indices decreased at the early postoperative stages, especially in patients suffering from severe inflammation. These results compared with the clinical indices of intoxication, one can infer on the major role of medium mass molecules in the increased blood toxicity in these patients. This was confirmed by the analysis of correlation and regression relationships between hepatic functional testing and blood toxicity. PMID- 2326811 TI - [Principles of the plastic replacement of tissues in patients with head and neck tumors]. AB - Basing on their experience, including 619 plastic surgeries for tumors of the head and neck, 412 (66.6%) of these being performed simultaneously with destructive operations, the authors validate the necessity of simultaneous plasty. They present the scheme for replacement of various defects in oncologic patients and describe some aspects of primary bone plasty in 23 patients. PMID- 2326812 TI - [Dentists, be careful--AIDS!]. PMID- 2326813 TI - [Potentials of orthopantomography in the diagnosis of the late stages of cancer of the maxilla]. AB - X-ray investigation was performed in 51 patients with maxillary cancer grades III to IV and the diagnostic capacities of orthopantomography were assessed in juxtaposition to other conventional X-ray techniques (tomography and various projection x-rays). Analysis of the data suggests that the technique is of major diagnostic importance. Its broad introduction will allow to reduce the number of x-ray investigations without losses in diagnostic information. PMID- 2326815 TI - [Clinico-immunological parallels in intolerance of dentures of dissimilar metal alloys]. AB - The presence of dissimilar metal incorporations in the mouth leads to the formation of local immune response, manifesting by increased levels of secretory IgA, IgM and IgG in the saliva. Though to essential differences in the mean values of the immunity parameters are detectable, the findings of discrete dynamic analysis of the immune profile of subjects with dissimilar metal incorporations in the oral cavity evidence a complex alteration of the humoral immunity. PMID- 2326814 TI - [Experience in treating the palatine position of the teeth]. AB - The results of management of the palatine position of the teeth with the use of removable and permanent designs of orthodontic apparatuses are analyzed. The terms of treatment of the palatine position of the teeth with permanent devices differed but little from the terms of treatment with removable devices. PMID- 2326816 TI - [Clinical manifestations and treatment of vertical deformities of the dental arches and bite in adults]. AB - Clinical manifestations and management of vertical deformation of the dentitions and occlusion were studied in 75 adult patients. Basing on the clinical picture of the condition, 3 forms and 4 degrees are distinguished. The treatment of the condition is multiple-modality with due consideration for the form and severity of the deformation. PMID- 2326817 TI - [The level of consumption of sweets by the population and dental caries]. AB - Examinations of 711 subjects of various age, sex, and social status, rural and urban residents, have shown that about 95% of the population are aware of the hazardous effects of sweets on the teeth. However more than a half of the examinees abuse sweets, this resulting in a higher incidence of caries. The most frequent sweet-eaters are children, women, urban workers, and rural employees. PMID- 2326818 TI - [Intraosseous administration of thymalin in the combined treatment of children with acute odontogenic osteomyelitis]. AB - Experience gained in the treatment of 63 children has demonstrated the validity of bone perforation and intraosteal drug lavage in a complex of therapeutic measures for acute mandibular odontogenic osteomyelitis running an unfavorable course. Incorporation of immunostimulant thymalin in the solutions used for intraosteal lavage of the inflammation focus in this condition is conducive to normalization of the cellular and humoral immunity and liquidation of the pathologic process without destruction of the bone tissue. PMID- 2326819 TI - [The incidence of the development of congenital clefts of the upper lip and palate in relation to blood group among the inhabitants of the provinces of the People's Republic of China]. AB - Examinations of patients with cleft lip and palate have revealed that this abnormality is most frequent in subjects with blood group A(II), that may be considered as a factor of risk of developing this condition. PMID- 2326820 TI - [The importance of the thermometric method for assessing the function of mucoperiosteal flaps in uranostaphyloplasty with/without transection of the neurovascular bundles in the rehabilitation of patients with congenital cleft palate]. AB - The nature and degree of reflow to the mucoperiosteal flaps was evaluated using a distant thermometry of the cleft palate in 67 children under uranostaphyloplasty and in early postsurgical period. In extracting the neurovascular bundles from their channels heat reflow to the palate was more fast and pronounced than with the bundles sectioned. PMID- 2326821 TI - [Characteristics of the structure of the palatine suture and interalveolar septum in normal children and in diastema]. AB - The palatine suture is wider in 6-14-year-old children with diastema than in normal ones; this suture is commonly direct and rarely tortuous. This may be due to its inadequate ossification. The width of the diastema does not depend on the suture width. An acuminate interalveolar septum predominates in normal children, but diastema and the child's age are conducive to its flattening. Orthodontic treatment normalizes the width of the palatine suture and the shape of the interalveolar septum, but in many patients the results are not stable. PMID- 2326822 TI - [A comparative evaluation of the traumatic nature of various methods of uranostaphyloplasty]. AB - The authors compare the intensities of nociceptive stimulation and blood loss volumes in children subjected to radical uranostaphyloplasty involving the use of all the elements of the technique and to its sparing modifications. The level of pain aggression, blood loss volume, and mean length of the operation were lower with the sparing methods than with the traditional one, this leading to a conclusion on the lower traumatism of the sparing uranostaphyloplasty technique for the body. PMID- 2326823 TI - [The importance of indices in epidemiologic research on periodontal diseases]. PMID- 2326824 TI - [The work productivity of the dentist in cleaning the oral cavity with the use of intravenous premedication]. PMID- 2326825 TI - [Intensification of the research work of a student dentistry society]. PMID- 2326826 TI - [The use of an improved method of comparative dispersion of birefringence for research on dental enamel mineralization]. AB - A number of modifications were made in the double refraction comparative dispersion techniques, permitting a quantitative analysis of apatites. These modifications are related to some features of monochromator employment, to the method of the compensator graduation, and to the mathematical processing of the measurement results, and they have essentially simplified the original technique and made it more reliable. The study has revealed that applications of 3% remodent solution followed by coating the teeth with 3% remodent-containing cyanacrylate lacquer increase calcium content in the enamel by 1.03-1.28%. Treatment with fluoride lacquer results in a lesser rise of Ca content, and single applications of 3% remodent solution are conducive to but a negligible increase of Ca content in the enamel surface layer only within the first day after exposure. Combined application of remineralization means increased phosphorus content in the enamel surface layer as well. PMID- 2326827 TI - The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats. AB - Ingestion of licorice or treatment with chemical derivatives of glycyrrhetinic acid (GA), an active principle of licorice, can cause hypertension, sodium retention, and hypokalemia. Although GA has been shown to inhibit 11 beta hydroxysteroid dehydrogenase, it may not be the only hepatic enzyme affected by this licorice derivative. Therefore, we studied the effects of GA on other major hepatic steroid-metabolizing enzymes from adrenalectomized male rats using aldosterone as the substrate; namely, delta 4-5 alpha- and delta 4-5 beta reductases and 3 alpha- and 3 beta-hydroxysteroid dehydrogenases (3 alpha- and 3 beta-HSD). From these in vitro studies, we demonstrated that GA does not affect either microsomal 5 alpha-reductase or cytosolic 3 alpha-HSD activity. However, GA is a potent inhibitor of cytosolic 5 beta-reductase; the K(is) and K(ii) were calculated from enzyme kinetic analysis to be 6.79 and 5.41 microM, respectively, using the Cleland equation, indicating that GA is a noncompetitive inhibitor of aldosterone. In addition, GA specifically inhibited microsomal 3 beta-HSD enzyme activity by what appears to be a competitive inhibition mechanism, causing a build-up of the intermediate, 5 alpha-dihydroaldosterone (DHAldo). Thus, this study has indicated that GA has a profound effect on hepatic ring A-reduction of aldosterone. Inhibition of 5 beta-reductase and 3 beta-HSD results in decreased synthesis of both 3 alpha, 5 beta-tetrahydroaldosterone (THAldo) and 3 beta, 5 alpha-THAldo and, hence, accumulation of aldosterone and 5 alpha-DHAldo, both potent mineralocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326828 TI - Synthesis and testing of 17a beta-hydroxy-7 alpha-methyl-D-homoestra-4,16-dien-3 one: a highly potent orally active androgen. AB - The title compound, 17a beta-hydroxy-7 alpha-methyl-D-homoestra-4,16-dien-3-one (3), was synthesized in five steps (17% overall yield) from 7 alpha-methylestrone methyl ether (5) and was found to possess oral androgenic activity, in excess of other known androgens, without using 17 alpha-alkyl substitution. PMID- 2326829 TI - Synthesis of 17 beta-(3'-thiophenyl)-5 beta-androstane-3 beta,14 beta-diol 3-D glucopyranoside, an anti-inotropic cardiac glucoside. AB - In a continuing effort to synthesize cardiac glucoside analogs with modified 17 beta-functional groups for pharmacologic testing, we used 3 beta-benzyloxy-5 beta androst-15-en-17-one as an efficient intermediate. This report describes a preparation of 17 beta-(3'-thiophenyl)-5 beta-androstane-3 beta,14 beta-diol 3-D glucopyranoside. PMID- 2326830 TI - Aromatase inhibition by R 76 713: a kinetic analysis in rat ovarian homogenates. AB - Reaction kinetics of the aromatase enzyme and of a new nonsteroidal aromatase inhibitor, R 76 713 (6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)-methyl]-1-methyl 1H- benzotriazole), were studied in ovarian homogenates obtained from pregnant mare's serum gonadotropin (PMSG)-injected female Wistar rats. The Km (Michaelis constant) of the aromatase enzyme with androstenedione as the substrate was 47 +/ 13 nM; for testosterone as the substrate, a value of 159 +/- 10 nM was found. In the presence of increasing concentrations of R 76 713, the Km increased while the Vmax (maximal velocity of enzyme-catalyzed reaction) remained unchanged. Using androstenedione and testosterone as the substrate, Lineweaver-Burk analysis of the data showed a Ki (dissociation constant of the enzyme-inhibitor complex) for R 76 713 of 0.7 +/- 0.3 nM and 1.6 +/- 0.4 nM, respectively. R 76 713 appeared to competitively inhibit the rat ovarian aromatase. PMID- 2326831 TI - Effects of social isolation and the time of day on testosterone levels in plasma of C57BL/6By and BALB/cBy mice. AB - Adult male C57BL/6By and BALB/cBy mice were housed either in large groups (20 per cage) or individually, and levels of plasma testosterone were measured in samples taken in the morning (9 to 10 A.M.) and in the evening (9 to 10 P.M.). No significant strain differences were found in testosterone levels, but the mean testis weight was significantly higher in the BALB/cBy strain. Two-way analysis of variances of pooled plasma testosterone data showed that social isolation of males results in a significant increase in A.M. (but not P.M.) testosterone concentrations and increased testis weight in both strains. Our results suggest that differential housing of a social species can affect testicular function. Since testicular function can also be influenced by the time of day, the question is raised whether the expression of circadian variation in plasma testosterone level is dependent on population density. PMID- 2326832 TI - The anticoagulant effect of hexolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta yl)-6-hydroxyhexylamine, another amino-estrogen with prolonged anticoagulant effect. AB - The anticoagulant and estrogenic effects of hexolame, N-(3-hydroxy-1,3,5(10) estratrien-17 beta-yl)-6-hydroxyhexylamine, are described. A single subcutaneous injection of hexolame in adult and infant male mice produced dose-dependent increases in blood clotting time which could be observed even after 2 days. In ovariectomized mice, hexolame produced vaginal cornification (estrogenic response). The data suggested that if used in the treatment of prostatic cancer, hexolame, like prolame, would not induce cardiovascular accidents. It could also be useful in the prevention of thrombosis. PMID- 2326833 TI - Effects of capsular or thalamic stroke on metabolism in the cortex and cerebellum: a positron tomography study. AB - We used positron emission tomography to study the cortical and cerebellar metabolic rates in 21 strictly selected patients with pure internal capsular infarct (n = 8), thalamocapsular hemorrhage (n = 6), or pure thalamic stroke (n = 7). Significant diffuse ipsilateral cortical hypometabolism relative to 62 controls free of cerebrovascular risk factors was frequently, although not consistently, found in the 13 patients with thalamocapsular or thalamic lesions and neuropsychological impairment but was absent from the eight patients with pure internal capsule infarct and free of neuropsychological deficit. These data suggest that damage to the thalamus or the thalamocortical projections is important in the development of ipsilateral cortical hypometabolism and that the latter may underlie the associated neuropsychological impairment. Significant contralateral cerebellar hypometabolism relative to 49 controls was found in three of six patients with pure internal capsule infarct, suggesting a pathogenetic role for the corticopontocerebellar system. However, the occurrence of hypometabolism in two of six patients with thalamic lesions indicates that this phenomenon may also result either from damage to the ascending cerebellothalamocortical system or indirectly from hypofunction of the cerebral cortex. No systematic association was observed between crossed cerebellar hypometabolism and ipsilateral ataxia. PMID- 2326834 TI - Carotid transient ischemic attacks and normal investigations: a follow-up study. AB - Reports on the long-term prognosis of patients with transient ischemic attacks and normal angiograms have revealed variable results, some suggesting a good prognosis while others report an outcome no different from that of patients with transient ischemic attacks and atherosclerotic vascular narrowing. Normal cerebral angiograms do not exclude disease in the heart or hematologic disorders. The prognosis for patients with transient ischemic attacks, normal angiograms, and normal results of cardiac and hematologic investigations is not known. We report our experience with 43 patients (26 men and 17 women, mean age 55.6 years) with transient ischemic attacks and normal findings on all investigations (including angiography, cranial computed tomography, echocardiography, and Holter monitoring). The patients were followed for a mean of 4.43 years. Six patients had recurrent transient ischemic attacks and six developed angina pectoris. No patient developed a stroke. In the presence of normal cerebral, cardiac, and hematologic findings, the long-term prognosis of patients with transient ischemic attacks is good. However, the development of cardiac disease during follow-up could not be predicted using the available diagnostic methods. PMID- 2326835 TI - Prospective study of lacunar infarction using magnetic resonance imaging. AB - Using computed tomography and magnetic resonance imaging, we prospectively studied 100 patients hospitalized with a lacunar infarct. Our aim was to evaluate the capabilities of magnetic resonance imaging in the detection and delineation of lacunes in a project of clinicotopographic correlations. Seventy-nine patients had a classic lacunar syndrome; 35 had pure motor stroke, 26 had ataxic hemiparesis, seven had sensorimotor stroke, and 11 had pure sensory stroke. A miscellaneous group of 21 patients had less typical lacunar syndromes, primarily with brainstem signs and symptoms. Among a total of 153 lacunes, magnetic resonance imaging detected at least one lacune appropriate to the symptoms in 89 patients. In 16 patients at least two lesions correlated with the clinical features, and precise clinicotopographic correlations were possible in 68 patients. Magnetic resonance imaging was more effective when it was performed a few days after the stroke. Lesions causing different types of lacunar syndromes had significantly different volumes, suggesting that the size of the lesion may influence clinical features. Magnetic resonance imaging may be the imaging technique of choice in the study of lacunar syndromes. PMID- 2326836 TI - Focal headache during balloon inflation in the internal carotid and middle cerebral arteries. AB - Although a number of reports are available on the occurrence of headache in patients with ischemic cerebrovascular disease, most studies have recorded the frequency but not the specific sites of the pain. We report 18 patients who underwent balloon inflation in the distal internal carotid artery and middle cerebral artery stem during embolization therapy for intracerebral arteriovenous malformations. Eleven patients had reproducible patterns of headache during balloon inflation. Inflation in the proximal middle cerebral artery stem produced pain primarily in the ipsilateral temple, that in the middle of the middle cerebral artery stem produced pain referred primarily retro-orbitally, and inflation in the distal middle cerebral artery stem produced pain referred primarily to the forehead. Experimental studies have demonstrated similar patterns of referred pain. The fact that these areas of referred pain are so reproducible is of potentially great clinical importance in the approach to management of patients with cerebrovascular disease. PMID- 2326837 TI - Transesophageal echocardiography in the detection of intracardiac embolic sources in patients with transient ischemic attacks. AB - Using both precordial and transesophageal echocardiography, we studied 72 consecutive patients with a recent unequivocal transient ischemic attack or nondisabling stroke to determine the relative value of the two techniques for detecting potential intracardiac sources of cerebral emboli. Group 1 (n = 53) patients had no clinical cardiac abnormality, and group 2 (n = 19) patients had abnormal cardiac findings upon clinical examination. In group 1, precordial echocardiography detected an abnormality in only one patient (aortic valve thickening) but transesophageal echocardiography defined morphologic abnormalities in five patients (one with a left atrial appendage mass lesion, one with aortic dissection, one with mitral valve prolapse, one with a mitral leaflet mass lesion, and one with aortic valve thickening). In group 2, both precordial and transesophageal echocardiographic studies were normal in 13 patients, while both were abnormal in the remaining six patients. Five of these six patients had pathologic left atrial and/or left ventricular dilatation, but only transesophageal echocardiography defined a left atrial appendage thrombus in two of the six. The sixth patient had mitral chordal rupture, seen on both precordial and transesophageal echocardiography. In addition, in 32 of the 72 patients transesophageal echocardiography identified widespread thoracic aortic atherosclerotic plaques not visualized by precordial echocardiography. We conclude that transesophageal echocardiography significantly increases the yield in visualizing potential intracardiac sources of emboli compared with precordial echocardiography. However, the precise clinical value of the former in the management of such patients requires further study as the number of abnormal transesophageal echocardiographic findings is not high and a causative relation with transient ischemic attacks cannot be proven. PMID- 2326838 TI - Platelet thromboxane release after subarachnoid hemorrhage and surgery. AB - We studied adenosine diphosphate-induced platelet aggregation and the associated release of thromboxane B2 in platelet-rich plasma from 88 patients with subarachnoid hemorrhage and 26 healthy controls. During the first 3 days after subarachnoid hemorrhage, the patients showed significantly decreased (p less than 0.05) platelet aggregability and thromboxane release relative to the controls, but these effects disappeared in a few days. Platelet count increased for 3 weeks after subarachnoid hemorrhage. Surgery in 67 patients was followed by significant increases in platelet aggregability (p less than 0.05) and thromboxane release (p less than 0.001). Greatest thromboxane release was found in the eight patients showing delayed (postoperative) ischemic deterioration with a permanent neurologic deficit. Although platelet hyperaggregability and increased thromboxane release were particularly prominent in these eight patients, the role of these hematologic parameters in the pathogenesis of delayed ischemic deterioration remains unclear. PMID- 2326839 TI - Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke. AB - Homocyst(e)ine refers to the sulfur-containing amino acids homocysteine, homocystine, and homocysteine-cysteine mixed disulfide, which normally exist in plasma in both the free and protein-bound forms. Marked hyperhomocyst(e)inemia is associated with well-recognized complications of occlusive thrombotic events and a characteristic syndrome. It is less clear whether mild to moderate elevations in plasma homocyst(e)ine concentrations (i.e., 1.5-5-fold increases) also represent a risk factor for stroke and, if so, whether it is independent of other recognized risk factors. To examine these questions we compared the plasma homocyst(e)ine levels in 41 patients with acute strokes, 27 patients with transient ischemic attacks, 31 patients with recognized risk factors for but no recent symptoms of cerebrovascular disease, and 31 normal volunteers (controls). Plasma homocyst(e)ine concentration was moderately but significantly higher in the patients than in the controls (p less than 0.0001). Approximately 30% of the patients had homocyst(e)ine levels higher than the controls. No relation was found between homocyst(e)ine concentration and other recognized stroke risk factors or stroke type; however, a positive correlation was found between serum uric acid and plasma homocyst(e)ine levels. These data suggest that a moderately elevated plasma homocyst(e)ine concentration may be an independent risk factor for cerebrovascular disease. PMID- 2326840 TI - Chronic cerebral blood flow changes following experimental subarachnoid hemorrhage in rats. AB - Experimental subarachnoid hemorrhage was induced in 52 adult male Wistar rats by microsurgical transclival basilar artery puncture. Telencephalic blood flow measured in 24 rats with subarachnoid hemorrhage was compared with that in 23 sham-operated rats and 10 unoperated control rats using the [14C]butanol indicator fractionation technique. Telencephalic blood flow was significantly less in the rats with subarachnoid hemorrhage than in the sham-operated rats 3 (78.7 +/- 6.9 [n = 7] and 112.0 +/- 8.5 [n = 8] ml/100 g/min, respectively; p less than 0.01), 7 (74.9 +/- 5.1 [n = 9] and 112.6 +/- 4.6 [n = 8] ml/100 g/min, p less than 0.001), and 14 (81.9 +/- 6.0 [n = 8] and 104.1 +/- 5.4 [n = 7] ml/100 g/min, p less than 0.01) days after surgery. Telencephalic blood flow in unoperated controls (114.7 +/- 4.9 ml/100 g/min) did not differ significantly from sham-operated rats. Clinically, the 52 rats with subarachnoid hemorrhage were indistinguishable from 32 sham-operated rats. Postmortem examinations in 10 rats used in a preliminary investigation demonstrated significant blood clot in the basal cisterns 2 hours after basilar artery puncture. Intracranial pressure was slightly elevated (2.3 mm Hg over baseline) 30 minutes after the hemorrhage (n = 7), but when measured 3 (n = 3) or 7 (n = 3) days after surgery it had returned to baseline. Histologic examination of the brains from 10 rats subjected to subarachnoid hemorrhage 7 (n = 5) or 14 (n = 5) days before sacrifice revealed no evidence of cerebral ischemia or vasculopathic changes in the cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2326841 TI - Hemorrhagic infarct induced by arterial hypertension in cat brain following middle cerebral artery occlusion. AB - The purpose of this experiment was to determine whether an acute rise in brain perfusion pressure causes hemorrhagic transformation of an infarct without a reopening of the occluded artery. We raised the blood pressure of 22 cats by aortic obstruction 5-24 hours after transorbital middle cerebral artery clipping; hemorrhagic infarcts were induced in 11. Mean arterial blood pressure increased by 57.2 +/- 16.9 mm Hg (mean +/- SD) in the 11 cats with hemorrhagic infarcts and by 40.4 +/- 16.9 mm Hg in the 11 remaining cats with pale brain infarcts (p less than 0.05). Induction of hypertension increased regional cerebral blood flow in the ischemic cortical gray matter more in three cats with hemorrhagic infarcts than in seven with pale infarcts. Our results demonstrate that hemorrhagic transformation of an infarct can be induced by a rapid increase in perfusion pressure to brain tissue already exposed to focal ischemia. We also suggest that the restoration of blood flow through leptomeningeal collaterals plays an important role in the pathogenesis of hemorrhagic infarction in cases without reopening of occluded arteries. PMID- 2326842 TI - Prevention of ischemic-hypoxic brain injury and death in rabbits with fructose 1,6-diphosphate. AB - Fructose-1,6-diphosphate has been shown to improve neurologic recovery following resuscitation from cardiac arrest and to restore brain electrical activity during hypoglycemic coma in rabbits. In view of these findings, we determined whether fructose-1,6-diphosphate protects the brain during ischemia-hypoxia. We subjected 16 rabbits to hypotension, hypoxemia, and bilateral common carotid artery occlusion. Five minutes after the onset of isoelectric electroencephalograms, seven randomly selected rabbits received 10% fructose-1,6-diphosphate (350 mg/kg bolus followed by 10 mg/kg/min infusion for 90 minutes) and the remaining nine rabbits (controls) received an equal volume of 1.5% NaCl (3.5 ml/kg bolus followed by 0.1 ml/kg/min infusion for 90 minutes). After isoelectricity lasting 7.86 +/- 0.8 minutes (mean +/- SEM) in the treated group and 6.44 +/- 0.38 minutes in the control group, the rabbits were reinfused with autologous shed blood and reoxygenated and the carotid artery occluders were removed. Treated rabbits recovered electrical activity more rapidly than the controls (p less than 0.005), and all seven treated rabbits survived. Only two controls (22%) survived (p less than 0.001), and they were severely disabled. Histology showed extensive cortical necrosis and focal necrosis in the hippocampi and cerebellum of brains from the two surviving controls. Brains from two treated rabbits exhibited minimal neuronal loss limited to the neocortex, and the brains from the remaining five treated rabbits were normal. This study suggests that fructose-1,6 diphosphate protects the brain from ischemic-hypoxic insults. PMID- 2326843 TI - Increased cerebral lactate output to cerebral venous blood after forebrain ischemia in rats. AB - Increased cerebral lactate levels are a well-known aspect of the sequelae of the metabolic derangements that follow cerebral ischemia. A new technique has recently become available to sample cerebral venous blood from the superior sagittal sinus on a long-term basis in conscious rats. We report the applicability of this method to assess serial biochemical responses to brain injury. Serum samples were obtained from the superior sagittal sinus, the common carotid artery, and the external jugular vein of nine anesthetized rats before and up to 7 days after 10 minutes of forebrain ischemia was produced by carotid occlusion and hypovolemic hypotension (mean arterial blood pressure 50 +/- 4 mm Hg). The cerebral venous-arterial difference in serum lactate concentration was increased for up to 3 hours after ischemia, while there was no significant change in the difference in serum lactate concentrations in the common carotid artery and the external jugular vein. This indicates an elevated output of lactate from brain tissue to blood, detectable only in the superior sagittal sinus, which underlines the usefulness of the technique. We observed a persistent elevation in brain lactate production after virtually complete recovery from the acute insult. PMID- 2326844 TI - Three cases of spontaneous extracranial vertebral artery dissection. AB - We describe three cases of extracranial vertebral artery dissection that are unusual in both their modes of presentation and their associations with other pathologic conditions. The first patient had Marfan's syndrome and migraine; his dissection was asymptomatic and was diagnosed by chance at the time of repeat angiography following a previous internal carotid artery dissection. The second patient had systemic lupus erythematosus and presented with a subarachnoid hemorrhage attributed to an intracranial vertebral artery dissection by the demonstration of an extracranial dissection. The third patient had a minor basilar artery stroke in which dissection had occurred beside a congenital hemivertebra deformity. PMID- 2326845 TI - Cerebrovascular disease in Ehlers-Danlos syndrome type IV. AB - We describe two patients with cerebrovascular complications of Ehlers-Danlos syndrome type IV. A 16-year-old girl with spontaneous internal carotid artery dissection and a 46-year-old woman with aneurysmal subarachnoid hemorrhage and multiple aortic dissections were both deficient in collagen type III, analyzed in cultured skin fibroblasts. To our knowledge, spontaneous carotid artery dissection associated with collagen type III deficiency has not been reported previously. Early clinical recognition of this syndrome is of great importance in view of the hazards of angiography and surgery. Collagen type III deficiency plays a role in the pathogenesis of intracranial saccular aneurysms and may also be involved in the pathogenesis of carotid cavernous fistulas and dissections of the cervical arteries. PMID- 2326846 TI - Special report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular diseases III. PMID- 2326847 TI - Assessing risks associated with carotid endarterectomy. PMID- 2326848 TI - Correlation of carotid bruits and carotid atherosclerosis. PMID- 2326849 TI - Reversible experimental middle cerebral artery occlusion. PMID- 2326850 TI - The today's O.R. Nurse 1990 salary survey. PMID- 2326851 TI - Today's OR Nurse 1990 salary survey. Examining the results. PMID- 2326852 TI - Parathyroidectomy: maintaining calcium homeostasis. AB - 1. Meticulous homeostasis is important as the surgeon locates the parathyroid glands. 2. Multiple specimens must be labeled and sent to pathology to aid in the identification of parathyroid tissue. 3. Some of the removed parathyroid tissue is often reimplanted in a neck or arm muscle, and some may be frozen for future use. PMID- 2326853 TI - Nursing theory. Nightingale & Roy--a comparison of nursing models. AB - 1. Today, in an effort to develop the profession of nursing, nurses are working to base nursing actions on a theoretical model. 2. There are four reemerging themes evidenced in both the Nightingale and Roy models, including environment, person, health, and nursing. 3. The Roy and Nightingale models share more similarities than differences: both describe their metaparadigm (ie, environment, person, health, and nursing) in relation to their models. PMID- 2326854 TI - Resource management. PMID- 2326855 TI - A manager's challenge: enforcing OR policy. PMID- 2326856 TI - Nursing liability for patient falls. PMID- 2326857 TI - The OR nurse manager. Blending an autocratic and democratic approach to lead effectively. PMID- 2326858 TI - Biliary lithotripsy--a smashing solution. AB - 1. To ensure that the energy of the shock wave is not dissipated before it reaches the stone, an airtight seal must be established between the patient and the acoustic lens that separates the water in the spark gap chamber from the patient. 2. Laboratory tests and ultrasound exams must be done at 24 hours and 1 month intervals for 6 months after treatment to determine if the patient is stone free. 3. Patients treated with biliary lithotripsy have less pain, a shorter recovery period, and less chance of infection than those who have cholecystectomies. PMID- 2326859 TI - Attitudes are contagious. What are you spreading around? AB - 1. High scrutiny, rapid change, and demands for higher levels of production and performance produce stress and uncertainty, which can exact a severe toll on individual morale, as well as the efficiency of a work unit or entire organization. 2. Negative rumors are spread when needed information is limited, and when individuals are anxious, frustrated, hurt, or angry; each person either "poisons the well" or offers encouraging antidotes. 3. Those who learn active listening, accompanied by insightful understanding and compassion, are the organization's healers, helpers, and positive leaders. PMID- 2326860 TI - Programmed cell death in the epidermis. PMID- 2326861 TI - Intraoperative hemodynamics in liver transplantation comparing orthotopic with heterotopic transplantation in the pig. AB - The intraoperative hemodynamic changes and several graft function parameters were studied comparing orthotopic liver transplantation with auxiliary partial liver transplantation (APLT) in the pig. Thirty-one Yorkshire pigs (ca. 25 kg b.w.) were randomly allocated to OLT (n = 16) or APLT (n = 15). During the construction of portal anastomosis the median cardiac output dropped to 67% of the initial value in OLT and to 49% in APLT (P less than 0.02). Median duration of the portal flow interruption was shorter in APLT: 15 min versus 48 min in OLT (P less than 0.002). After unclamping of the aorta, the median systolic blood pressure dropped to 75 mmHg in OLT and to 90 mmHg in APLT (P less than 0.02). APLT is less time consuming: median duration of transplantation was 128 min versus 165 min in OLT (P less than 0.002). SGOT levels were lower in APLT than in OLT (median SGOT on the first postoperative day 67 was IU/L versus 177 IU/L, P less than 0.002). It is concluded that APLT is a shorter procedure than OLT with a shorter portal flow interruption, being less offensive to the recipient. PMID- 2326862 TI - The course of untreated acute rejection and effect of repeated anti-CD3 monoclonal antibody treatment in rhesus monkey liver transplantation. AB - The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN18) was studied in a rhesus monkey model. Eight RhLA-mismatched monkeys received initial postoperative immunosuppression with CsA/prednisolone for 28 days. After cessation, acute rejection occurred in all animals (days 28-50). Control animals (n = 3) receiving no rejection treatment developed a chronic progressive rejection and died at days 112-160. In the animals treated with FN18 (n = 5), the first acute rejection was successfully reversed. T lymphocytes were cleared from the peripheral blood and the graft. Increased class I and class II MHC-antigens on hepatocytes were reduced to normal levels within 5 days of treatment. The second rejection treatment remained ineffective in two animals with antiidiotypic antibodies to FN18 but was successful in two animals with a low antimouse response. These four animals survived 160-509 days. The results have a number of implications regarding the course of untreated rejection in human liver transplant recipients and repetitive rejection treatment with monoclonal antibodies. PMID- 2326863 TI - Orthotopic liver transplantation with hepatic artery anastomoses. Hemodynamics and response to hemorrhage in conscious rats. AB - Orthotopic liver isotransplantation was performed in one group of Lewis rats using cuffs for the portal vein and the infrahepatic vena cava, stents for the hepatic artery and the bile duct. Three other groups were also investigated: group A, normal rats; group B, sham-transplanted rats (clamping of the vessels, washing of the liver, placing cuffs around the portal vein); and group C, sham transplanted rats with ligature section of the hepatic artery. Blood-flow measurements were performed, 1 week after the surgical procedure, with the radioactive microsphere method in conscious animals. Transplanted rats exhibited significant (ANOVA, P less than 0.05) increase in cardiac index and decrease in mean arterial pressure and systemic vascular resistance. Blood flows of the portal territory and to the kidneys were not significantly modified. Arterial liver blood flow and arterial liver vascular resistance in rats with liver transplantation were not significantly different between normal and sham transplanted rats but were significantly different from rats with ligature of the hepatic artery. These results confirm the validity of the method used for vascular anastomoses. Hypotensive hemorrhage (2 ml/100 g bw) induced marked hemodynamic changes, but rats with liver transplantation when compared with normal and sham-transplanted rats exhibited the following: (a) significantly lower percentage of decrease in cardiac index and in mean arterial pressure; and (b) significantly higher renal and portal tributary blood flows. Plasma catecholamine concentrations and plasma volume were higher in rats with liver transplantation than in normal rats but were not significantly different from sham-operated rats. Histologic examination of the liver revealed slight portal edema in sham-operated rats and small necrotic areas in the liver, probably corresponding to the reperfusion injury, in rats with liver transplantation. In conclusion, the method described for the four vascular anastomoses allows functional perfusion of the transplanted liver. Rats with liver transplantation exhibited a hyperkinetic circulatory syndrome and an improved tolerance to hemorrhage. Changes in plasma catecholamine concentrations and in plasma volume did not account for the hemodynamic changes. PMID- 2326864 TI - Mechanism of oxygenation of pancreas during preservation by a two-layer (Euro Collins' solution/perfluorochemical) cold-storage method. AB - To clarify the mechanism of oxygenation of the pancreas during preservation by two-layer (Euro-Collins' solution [EC]/perfluorochemical [PFC]) cold-storage method, the pancreas viability in the canine model of the pancreatic autotransplantation and tissue concentration of adenosine triphosphate were examined after 24-hr preservation by original and modified two-layer methods with respect to the position of the pancreas and oxygen bubbling into the PFC. Namely, the pancreas was in EC and on the surface of PFC with (group 1, original method) or without (group 2) oxygen bubbling into PFC. The pancreas was floated in EC with oxygen bubbling into PFC (group 3); compared with simple cold storage of the pancreas in EC (group 4); and nonpreserved pancreas (control, group 5). The preserved pancreas grafts by each method functioned immediately after transplantation and maintained normoglycemia for at least 5 days except that 1 of 5 dogs in group 4 died of a cause unrelated to the pancreas graft. The functional success rates of groups 1, 2, 3, 4, and 5 were 100%, 100%, 100%, 80%, and 100%, respectively. It was clear that mitochondrial function was well-preserved during 24-hr preservation regardless of the preservation method. In the condition that the mitochondrial function is well-preserved the tissue concentration of ATP was mostly dependent on the tissue oxygenation. The tissue concentration of ATP of group 1, 7.92 +/- 1.06 mumol/g dry weight, was significantly higher than that of nonpreserved pancreas (group 5), 4.44 +/- 0.49 mumol/g dry weight (P less than 0.01). It was apparent that the two-layer method was excellent to supply oxygen to the pancreas and maintain high ATP concentration of the pancreas during preservation. In contrast, ATP concentration of the pancreas of group 2 was 1.83 +/- 0.30 mumol/g dry weight, and there was no significant difference between group 2 and group 4, 1.19 +/- 0.33 mumol/g dry weight, thus meaning that PFC was biologically inert without oxygenation. In addition, when the pancreas was not contacted with oxygenated PFC and floated in EC (group 3) ATP concentration of the pancreas, 2.24 +/- 0.90 mumol/g dry weight, was significantly lower than group 1 (P less than 0.01), and no significant different was found as compared to groups 2 and 4. It was essential that the pancreas was contacted with oxygenated PFC to maintain high ATP tissue concentration during preservation by the two layer method.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2326865 TI - Changing of hepatitis B virus markers in patients with bone marrow transplantation. AB - The hepatitis B virus (HBV) infection and its resulting hepatic abnormalities are very high in prevalence among the Taiwan population. They also seem to compose a major problem to patients subjected to bone marrow transplantation (BMT) due to intensive chemoradiotherapy. In this study, the sera of 42 patients were investigated before and after BMT to detect the presence of HBV markers and to test their liver function (LF). Being followed-up for 3-12 months after BMT, 12 out of 27 were found to have altered HBV markers according to the classification of the following: seroconversion of HBsAg, clearance of HBsAb, appearance of HBeAg, clearance of HBeAb, and acute hepatitis. Thirty-seven out of 42 patients (88.1%) were found in routine LF test to develop one or more abnormality; however, 90% of them turned normal within one year after BMT. Only one patient died of complications associated with fulminant hepatitis. In conclusion, the previous hepatic damage from HBV infection appears unlikely to increase the risk of posttransplant morbidity and mortality. PMID- 2326866 TI - Bone marrow transplantation for severe aplastic anemia. Effect of a preparative regimen of cyclophosphamide-low-dose total-lymphoid irradiation and posttransplant cyclosporine-methotrexate therapy. AB - Twenty-nine patients with severe aplastic anemia were entered into a study of pre and posttransplant immunosuppressive therapy for bone marrow transplantation. Four of twenty-five previously transfused recipients prepared with cyclophosphamide 200 mg/kg and total-lymphoid irradiation 3 Gy experienced graft failure, indicating that this regimen was inadequate to ensure sustained engraftment. Posttransplant treatment with cyclosporine and methotrexate resulted in an actuarial incidence for grade greater than or equal to 2 graft-versus-host disease of 22 +/- 16%. Actuarial survival was 78 +/- 15%. These data indicate that more effective treatment is necessary to prevent graft failure, but since many patients can be successfully retransplanted, overall survival is comparable to other recent studies. PMID- 2326867 TI - Prospective study of the occurrence of monoclonal gammapathies following bone marrow transplantation in young children. AB - We have prospectively studied the occurrence of monoclonal serum immunoglobulins in 38 recipients of BMT. Patients were young children with primary immunodeficiencies (n = 31), other inherited diseases (n = 4), leukemia (n = 2), or aplastic anemia (n = 1). Twenty-nine received an HLA-nonidentical marrow and nine an HLA-identical marrow. Serum monoclonal immunoglobulins were detected by the immunofixation method. Monoclonal immunoglobulins were found in 26 patients. Monoclonal components were more frequently detected in patients with primary severe T cell deficiencies (21/25) rather than in the other patients (6/13). In 7 of 29 recipients of HLA-nonidentical transplants, versus 0 out of 9 recipients of HLA-identical transplants, serum monoclonal immunoglobulins were found associated with a B lymphocyte proliferation syndrome due to an Epstein-Barr virus infection. In this group, monoclonal immunoglobulins were detected early, prior to the onset of the clinical syndrome. The simultaneous occurrence of several monoclonal immunoglobulins was more frequent in these patients, while monoclonal immunoglobulin concentrations increased faster, especially those of IgM isotype. These characteristics may allow in patients at risk (recipients with primary T cell immunodeficiencies and receiving HLA-nonidentical transplantation) an earlier diagnosis of B lymphocyte proliferative syndrome that may eventually lead to early and more efficient therapy. PMID- 2326868 TI - Herpes simplex virus infection in heart-lung transplant recipients. AB - We report our experience of herpes simplex virus infection in a series of 51 recipients of heart lung transplantation (HLT). Nine patients, all of whom were seropositive for the virus preoperatively, developed HSV infection. Seven episodes of culture-proved mucocutaneous HSV infection without evidence of pulmonary involvement occurred in four patients. Six episodes of HSV pneumonia were seen in a further five patients, one of whom died. Diagnosis of HSV pneumonia was by histological appearances on transbronchial biopsy, together with culture of lung tissue or bronchoalveolar lavage. Concomitant cytomegalovirus infection occurred in four patients. All patients who developed HSV pneumonia did so within the first two postoperative months; in four patients following augmented immunosuppression. We now suggest that HLT recipients who are HSV antibody-positive should receive prophylactic acyclovir for the first two months after surgery and at times of augmented immunosuppression. PMID- 2326869 TI - Primary nonfunction. Is there a contribution from the back table bath? AB - A persistent problem in orthotopic liver transplantation (OLT) is primary nonfunction (PNF) of the hepatic allograft. In most instances the cause of the failure is unknown. In an attempt to minimize these graft failure, modifications in the procurement and operative procedure have been investigated. One change in the procedure at the University of Nebraska Medical Center has been the monitoring of the temperature of the fluid in the back table bath during preparation of the donor liver. Our initial procedure involved creating an ice slurry of lactated Ringer's solution and ice slush in which the donor liver was then prepared. The temperature of this ice slurry was retrospectively found to be from -3 degrees C to -1 degrees C (group I). In this group there was a higher than-expected incidence of PNF. To investigate whether the temperature of the back table bath influenced the incidence of PNF, beginning with transplant No. 42 the preparation of the back table bath was modified. The bath was created by adding a small amount of PlasmaLyte slush to 2 L of PlasmaLyte (group II). The temperature of the bath was maintained at 2-4 degrees C. Data were collected on 100 consecutive liver transplants. All transplants were performed using standard techniques, the operation for the two groups differing only as described above. Transaminase levels were followed as an index of the allograft function and were expected to begin to normalize within 2-3 days after transplantation. While both groups display this trend, transaminase levels in group II were significantly lower postoperatively than group I levels (P less than 0.05). Preoperative values were similar. There were 7 PNFs in group I; 0 in group II (P less than 0.005). We feel that the change in the back table procedure has positively influenced the function of the hepatic allografts, and we conclude that transplant centers need to monitor the temperature at which all allografts are stored and prepared, and the cognizant that this may influence the postoperative function of the transplanted liver. PMID- 2326870 TI - The isolated perfused rat spleen. An original method for studying the function of hepatocytes transplanted into the spleen. AB - The aim of this study was to assess directly the function of isolated hepatocytes 1 year after transplantation into the spleen, using an original model of isolated rat-spleen perfusion. Three specific liver functions, albumin synthesis, indocyanine-green clearance, and antipyrine oxidation, were studied. Five x 10(6) isolated hepatocytes were injected into the spleen of syngenic Wistar-Furth rats. One year later, splenectomy was performed, and the splenic pedicle was carefully isolated in order to allow a selective ex vivo perfusion for 3 hr. De novo albumin synthesis was studied by qualitatively using immunoelectrophoresis and autoradiography, and quantitatively using (35S)-methionine incorporation in albumin. De novo albumin synthesis was observed in spleens containing transplanted hepatocytes but not in controls (P less than 0.001); (35S) methionine incorporation was significantly higher in spleens containing transplanted hepatocytes than in controls (132 +/- 67 cpm/spleen/hr vs. 14 +/- 6 cpm/spleen/hr, P less than 0.001). Antipyrine clearance was significantly higher in spleens with transplanted hepatocytes than in controls (67.4 +/- 4.9 microliters/min/g vs. 0.2 +/- 0.4 microliters/min/g, P less than 0.01). No statistically significant difference was observed with indocyanine-green clearance (4.2 +/- 6.0 microliters/min/g, vs. 5.2 +/- 5.1 microliters/min/g, P greater than 0.05); this was probably due to the absence of compartmentation between the sinusoid and biliary sectors in this model. In conclusion, using this original isolated rat-spleen perfusion model, it was directly observed that 1 year after transplantation, intrasplenic hepatocytes can perform two liver specific functions, i.e., de novo albumin synthesis and antipyrine clearance. PMID- 2326871 TI - Antigenicity of fresh and cryopreserved rat valve allografts. AB - Aortic valve allografts have demonstrated excellent clinical performance, but the importance of antigenic differences between donor and recipient is largely unknown. To determine the antigenicity of aortic valve grafts, rat aortic valves with a short portion of thoracic aorta were transplanted into the abdominal aorta of recipient rats. Valves were used immediately after harvest (fresh) or following cryopreservation. Three weeks after this procedure, the recipient rats received a skin graft from a rat of a strain syngeneic to that of the aortic valve donor. Additional groups of rats were subjected to sham operation (sham) followed three weeks later by skin grafting. Recipient rats were of the Lewis strain. Donor rats were of the Lewis, F344 (weakly allogeneic, RT1-compatible, non-RT1-incompatible), LBN F1 (moderately allogeneic, one-haplotype-identical and one-haplotype-incompatible at both the RT1 and non-RT1 loci), or BN (strongly allogeneic, RT1 and non-RT1-incompatible) strain. Time to skin graft rejection was measured. Among rats receiving the F344 grafts, the time to skin graft rejection (mean +/- SD) was sham: 9.1 +/- 1.0 days, fresh: 7.1 +/- 1.2 days, cryopreserved: 6.9 +/- 0.7 days. Among rats receiving the LBN F1 grafts, the corresponding times were sham: 7.8 +/- 0.8 days, fresh: 5.6 +/- 0.5 days, cryopreserved: 5.4 +/- 0.5 days. Among rats receiving the BN grafts, the corresponding times were sham: 7.1 +/- 0.3, fresh: 4.5 +/- 1.0 days, and cryopreserved: 4.3 +/- 0.7 days. Significant differences (P less than 0.05) existed between sham and fresh and between sham and cryopreserved, but not between fresh and cryopreserved. Significant differences (P less than 0.05) also existed between each histocompatibility grouping. It is concluded that aortic valve allografts in rats are antigenic and produce recipient sensitization. Cryopreservation does not diminish this sensitization. The degree of antigenicity is related to the degree of histoincompatibility between donor and recipient. Both RT1 and non-RT1 antigens appear to play a role in this process. PMID- 2326872 TI - Skin grafting in gynogenetic common carp (Cyprinus carpio, L.). The development of histocompatible clones. AB - The fate of skin allografts exchanged among heterozygous and homozygous gynogenetic common carp siblings, and among newly developed inbred strains and F1 hybrids, is described. Heterozygous gynogenetic offspring were produced by fertilizing eggs with UV-irradiated sperm and by treating the resulting zygote with a cold shock (0 degree C, 45 min). The temperature shock causes retention of the second polar body, which allows the eggs to develop into normal diploid fry. Homozygous gynogenetic offspring were similarly produced by using a heat shock (40 degrees C, 2 min), which suppresses the first mitotic division. Skin allografts exchanged among heterozygous gynogenetic carp exhibited prolonged survival, with some allografts (21.8%) surviving for over 28 days. Furthermore, a strong histocompatibility locus was seen to segregate in this group. In contrast, skin allografts exchanged among homozygous gynogenetic siblings were all rejected within 14 days (MST 9.4 days). New homozygous inbred strains, designated JJ and MM, were produced by gynogenetic reproduction of homozygous female carps, while F1 hybrids were produced by crossing of these homozygous females with homozygous male siblings. All grafts exchanged among members of the same strain were permanently accepted. Likewise grafts from homozygous strain members were accepted by fish from the related F1-hybrids, while the reverse grafts were rejected. These results provide evidence for the idea that in the carp histocompatibility genes exist at least one major locus and multiple minor loci, which are codominantly expressed. PMID- 2326873 TI - Characterization of the interstitial cellular infiltrate in experimental chronic cyclosporine nephropathy. AB - In a recently described rodent model of chronic cyclosporine nephropathy (CCN) (consisting of irregularly distributed areas of interstitial inflammation, interstitial fibrosis, and tubular atrophy) we have characterized the interstitial inflammatory cells. Using a modified avidin-biotin peroxidase technique, kidney tissue was examined with monoclonal antibodies directed against leukocyte-common antigen (LCA), T lymphocytes, T helper and T nonhelper lymphocytes, Ia (B cell marker), and macrophages. Injured cortex from cyclosporine-treated animals demonstrated increased numbers of T helper and B lymphocytes, macrophages, and cells bearing LCA. Cytotoxic (T nonhelper) cells were scant. Non-injured areas of cortex from CsA-treated animals demonstrated only a modest increase in macrophages when compared with vehicle controls and normal rats. We conclude that CCN in rodents is characterized by an interstitial inflammatory infiltrate of T helper cells, B cells, and macrophages. The role of these cells in the pathogenesis of CCN, however, remains speculative. PMID- 2326874 TI - Failure of cell surface expression of a class I major histocompatibility antigen caused by somatic point mutation. AB - The ability to down-regulate major histocompatibility complex class I antigen expression on allografts prior to transplantation would be expected to improve their survival in immunocompetent recipients. In order to identify genetic mechanisms that mediate attenuation of MHC class I antigen expression, we have begun characterizing H-2Kb surface null somatic cell variants derived from an H-2 heterozygous tumor cell line (H-2b X H-2d). These variants have sustained a modification in cell surface MHC phenotype, as evidenced by their failure to be recognized by both anti-H-2Kb antibodies and cytotoxic T lymphocytes. The mutant phenotype for one such variant (designated 69.9.15) was marked by the expression of abundant H-2Kb mRNA and immuno-precipitable H-2Kb protein in cell lysates. The failure in cell surface expression of the H-2Kb antigen was caused by a single base change (G to A transition) in exon 3, encoding the second external domain (alpha 2) of the H-2Kb molecule. The mutation resulted in the substitution of Tyr for Cys at amino acid position 164, thereby disrupting an intrachain disulfide linkage formed between Cys 101 and 164. In contrast to the wild-type H-2Kb gene, DNA-mediated transfer of the mutant H-2Kb gene into mouse L cell fibroblasts failed to result in cell surface expression of the H-2Kb antigen, although both the wild-type and mutant genes were transcribed to equivalent levels. These data indicate that a genetic event as limited as somatic point mutation can abrogate expression of a MHC class I antigen and provide support for the hypothesis that protein folding plays an important role in the cell surface expression of MHC class I molecules. PMID- 2326875 TI - The prospective value of the preoperative flow cytometric crossmatch assay in renal transplantation. PMID- 2326876 TI - Successful pregnancy in a renal transplant recipient with type I primary hyperoxaluria. PMID- 2326877 TI - Acute myelogenous leukemia in a renal allograft recipient receiving cyclosporine therapy. PMID- 2326878 TI - Interstitial pneumonia caused by Bordetella bronchiseptica in a heart transplant patient. PMID- 2326879 TI - Successful treatment of hepatic venoocclusive disease in a bone marrow transplant patient with orthotopic liver transplantation. PMID- 2326880 TI - Cyclosporine bioavailability in heart-lung transplant candidates with cystic fibrosis. PMID- 2326881 TI - Tolerance of cyclosporine oral capsules in a patient hypersensitive to standard oral and intravenous solutions of the drug. PMID- 2326882 TI - A comparison of University of Wisconsin and Euro-Collins' solutions for simple cold storage in non-heart-beating cadaveric kidney transplantation. PMID- 2326884 TI - Acute mesenteric small bowel ischemia in the rat. I. Protective effect of naloxone. PMID- 2326883 TI - A paradox in heart and lung rejection. PMID- 2326885 TI - Major histocompatibility complex-unrestricted tolerance induction in rats. PMID- 2326886 TI - A rabbit model for heterotopic cardiac transplantation. PMID- 2326887 TI - Serum transfer, anaphylactic shock, and the role of fetal calf serum. PMID- 2326888 TI - DNA dideoxy sequencing with T7 DNA polymerase: improved sequencing data by the addition of manganese chloride. PMID- 2326889 TI - Direct hybridization of biotin-labeled probes in dried agarose gels. PMID- 2326891 TI - Fourth International Symposium on Organ Procurement and Preservation. Minneapolis, Minnesota, September 18-20, 1989. PMID- 2326890 TI - Recovery of agarose for electrophoresis of DNA fragments. PMID- 2326892 TI - Receipt of shared organs at two geographically separate centers--the impact of UNOS. PMID- 2326893 TI - Implications of changing organ donor pool. PMID- 2326894 TI - Current practices of determining brain death in potential organ donors. PMID- 2326895 TI - Are early referrals of potential organ donors good or bad? PMID- 2326896 TI - Survey of attitudes of health care professionals toward organ donation. PMID- 2326897 TI - Donor family surveys provide useful information for organ procurement. PMID- 2326898 TI - An assessment of the impact of required request legislation on the availability of cadaveric organs for transplantation. PMID- 2326899 TI - Presumed consent law: results of its application/outcome from an epidemiologic survey. PMID- 2326900 TI - Organ procurement--the business perspective. PMID- 2326901 TI - Value of discussion groups in educating blacks about organ donation and transplantation. PMID- 2326902 TI - Evolution of the Colorado Organ Recovery Systems. PMID- 2326903 TI - The procurement of kidneys for transplantation in Scandinavia. AB - In countries with active renal transplant programs and wide acceptance criteria for transplant patients, the number of cadaveric donors is not, and probably never will be, sufficient to meet the demand for renal allografts. In general between 15 and 20 cadaveric donors PMP per year (maximum 23.7 in Denmark in 1986) have been available in the Scandinavian countries in the 1980s. In most other countries fewer donors are available, but there are regions where higher figures have been reached. Continuous registrations of potential cadaveric donors in Sweden have shown that the number of donors could increase by 40% to 60% if relatives of all medically suitable patients had given consent to organ donation. Since a public survey has shown that factual information on cadaveric organ donation and transplantation had a positive effect on the public's attitude, more public awareness programs are needed. Donor acceptance criteria are already broadly based, particularly with respect to age, and could probably not be further broadened without risking results after transplantation. A varying proportion of renal allografts from living donors are used in the Scandinavian countries. An increased use of living donors, related and unrelated, in the countries where few currently are used might help meet demand in the future. At present the need for nonrenal organs can be met, but as the programs for liver and heart transplantations are developed to reach their predicted levels, the current number of donors will most likely prove insufficient. PMID- 2326904 TI - Organ donation in the North Italy Transplant program. PMID- 2326905 TI - Organ procurement organization in the Basque autonomous community: present achievements and future prospects. PMID- 2326907 TI - Extending the criteria for cadaver kidney donors. PMID- 2326906 TI - Trans-Pacific sharing of kidneys requiring preservation for more than 50 hours: an analysis of 33 cases. PMID- 2326908 TI - The effect of donor source on the outcome of living related renal transplantation. PMID- 2326909 TI - Transplantation between husband and wife. PMID- 2326910 TI - Use of distant relatives and living unrelated donors: a strategy to increase the application of kidney transplantation to treat chronic renal failure. PMID- 2326912 TI - The value of systemic heparinization during living donor nephrectomy. PMID- 2326911 TI - ABO-incompatible living related donor criteria. PMID- 2326913 TI - Arginine vasopressin versus desmopressin for the treatment of diabetes insipidus in the brain dead organ donor. PMID- 2326914 TI - Influence of donor age on graft function in a single procurement center. PMID- 2326915 TI - Are pediatric donors well utilized? PMID- 2326916 TI - A comparison of pediatric versus adult cadaver donor kidneys for transplantation. PMID- 2326917 TI - Pediatric donors: still successful in adults. PMID- 2326918 TI - Age: a major determinant of renal dysfunction. PMID- 2326919 TI - The aging kidney donor: another answer to organ shortage? The Leuven Collaborative Group for Transplantation. PMID- 2326920 TI - Risk evaluation in the use of kidneys from elder organ donors for transplantation. PMID- 2326921 TI - Transplant of a polycystic kidney because of organ shortage. PMID- 2326922 TI - Factors influencing the recovery of extrarenal organs. PMID- 2326923 TI - Successful use of cadaver kidneys from diabetic donors for transplantation. PMID- 2326925 TI - Cadaver kidney transplantation using donors with hypertension in the North Italy Transplant program. PMID- 2326924 TI - Is the graft origin an important factor in the 'center effect' in kidney transplantation? PMID- 2326926 TI - The use of prenephrectomy histocompatibility testing to shorten cadaver kidney cold ischemia time. PMID- 2326927 TI - Local procurement with pulsatile perfusion gives excellent results and minimizes initial cost associated with renal transplantation. PMID- 2326928 TI - Objective numerical criteria for measurement of the severity of delayed graft function produced by different organ procurement and preservation techniques in renal transplantation. PMID- 2326929 TI - In situ dissection of cadaver kidneys. AB - Major anatomic injuries occurred in 18 of 151 (12%) en bloc kidneys. No injuries occurred among the in situ kidneys. The rates of delayed graft function were equal. All the kidneys removed by the in situ method were removed by one surgeon (ALH). The results are good enough to recommend the technique even without a randomized study. PMID- 2326930 TI - Outcome of kidney transplants requiring extensive endarterectomy. PMID- 2326931 TI - Transplantation of kidneys with fibromuscular dysplasia. PMID- 2326932 TI - Does the quality of early graft function influence the long-term outcome of cadaver renal transplantation? A case control study from a single institution. PMID- 2326933 TI - Abdominal aortic aneurysm repair after renal transplantation without extracorporeal bypass. PMID- 2326934 TI - An en bloc method for use of small pediatric cadaver kidneys in adult recipients. PMID- 2326935 TI - Transplantation of single pediatric cadaveric kidneys into adult recipients after prolonged preservation. PMID- 2326936 TI - Bench reconstruction of the graft arterial supply in liver transplantation. PMID- 2326937 TI - Imported hepatic allografts: a single center experience. PMID- 2326938 TI - Frozen section of liver biopsy for the evaluation of liver allografts. PMID- 2326939 TI - Predictive value of intraoperative liver biopsies of donor organs in patients undergoing orthotopic liver transplantation. AB - The evaluation of prerevascularization and postrevascularization biopsies in comparison with clinical and laboratory data has revealed a direct correlation between elevated PT and AST levels and pericentral and panlobular individual hepatocyte necrosis. No other significant correlations were determined when comparing selected histologic features to selected clinical laboratory values. In conclusion, these biopsies are of limited use in predicting subsequent allograft function in the absence of prominent individual hepatocyte or pericentral necrosis. PMID- 2326940 TI - Management of arterial anomalies encountered in split-liver transplantation. PMID- 2326941 TI - Maximal use of liver and pancreas from cadaveric organ donors. PMID- 2326942 TI - Simultaneous liver and pancreas procurement--a simplified method. PMID- 2326943 TI - Efficacy of simultaneous cadaveric pancreas and liver recovery. PMID- 2326944 TI - Combined liver/pancreaticoduodenal procurement effect on allograft function. PMID- 2326945 TI - Ultrasound investigation prior to organ donation. PMID- 2326946 TI - Plasma lecithin/cholesterol acyltransferase (LCAT) activity in multiple-organ donors: a predictor of allograft viability in clinical liver transplantation. PMID- 2326947 TI - The influence of donor hyperglycemia and other factors on long-term pancreatic allograft survival. PMID- 2326948 TI - Pulsatile perfusion preservation: early posttransplant dialysis requirement predicts rapid graft loss. PMID- 2326949 TI - Ultrastructural changes of different preserved human kidney allografts before and after reperfusion. PMID- 2326950 TI - The effect of halothane on reperfusion injury in renal tubules after cold storage. PMID- 2326951 TI - Selenium addition to the flush/preservation solution protects kidneys against oxidative stress during warm and cold ischemia. PMID- 2326952 TI - Glutathione depletion in cold-stored organs. PMID- 2326953 TI - Use of UW cold storage solution for machine perfusion of kidneys. PMID- 2326954 TI - Heat shock protects pig kidneys against warm ischemic injury. PMID- 2326955 TI - Better renal function with naloxone treatment following hemorrhage and brain death. PMID- 2326956 TI - Efficacy of allopurinol and ATP-MgCl2 in protecting against preservation/reperfusion injuries in a hypotensive canine renal autotransplant model. PMID- 2326957 TI - Importance of glutathione and adenosine in cold storage of the kidney. PMID- 2326958 TI - Mild hypothermia gives better functional preservation than cold or normothermic perfusion of rat kidneys. PMID- 2326959 TI - Experience with Belzer UW cold storage solution in human liver transplantation. PMID- 2326960 TI - UW solution improves duration and quality of clinical liver preservation. AB - Prolonged liver preservation (up to 17 hours) with UW solution had no adverse effect on perioperative blood loss or results of postoperative serum biochemistry studies. After use of this solution, biliary and vascular complications as well as evidence of histologic damage were less. The advantages of the extended preservation time permit liver transplantation to be done as a semi-elective procedure; more patients can be waiting at home instead of near the transplant center. The availability of UW solution also makes it possible to send grafts long distances throughout the nation. Furthermore, surgeons can arrange for backup patients in case the recipient proves to be inoperable. This capability should reduce organ wastage, even before the time limits of preservation with UW solution have been determined definitely. We feel that UW solution undoubtedly has improved both the duration and quality of liver graft preservation. PMID- 2326961 TI - Effect of extended preservation and reduced-size grafting on organ availability in pediatric liver transplantation. PMID- 2326962 TI - 31P nuclear magnetic resonance study of phospholipid metabolites in hypothermic preserved liver. PMID- 2326963 TI - Effect of acidosis during cold ischemic storage on liver viability following transplantation in the rat. PMID- 2326964 TI - Protective effect of allopurinol, catalase, or superoxide dismutase in the ischemic rat liver. PMID- 2326965 TI - Mouse liver metabolism after 24-hour and 48-hour cold preservation using UW, hydroxyethyl starch-free UW, and Euro-Collins solutions: A 31P, 13C NMR spectroscopy and biochemical analysis. PMID- 2326966 TI - Comparative evaluation of Euro-Collins, UW solution, and UW solution without hydroxyethyl starch in orthotopic liver transplantation in the rat. PMID- 2326967 TI - Effect of free radical scavengers in UW solution on pig liver preservation--a comparison with EC solution. PMID- 2326968 TI - Improved liver preservation with UW solution by chlorpromazine donor pretreatment. PMID- 2326969 TI - Evaluation of initial cooling solutions for liver preservation using isolated perfused rabbit liver. PMID- 2326970 TI - Primary hepatocyte culture--a model for the study of liver preservation. PMID- 2326971 TI - Histamine and xanthine oxidase in hepatic ischemia-reperfusion injury. PMID- 2326972 TI - Comparative analysis of colloid solutions for liver preservation: a bimodal distribution of UW solution on its protective effect. PMID- 2326973 TI - Influence of preservation time on the early function of pancreas transplants. PMID- 2326974 TI - 96-hour cold storage preservation of the canine pancreas. PMID- 2326975 TI - Successful 72-hour preservation of the canine pancreas. PMID- 2326976 TI - Adenosine and its role in cardioplegia: effects on postischemic recovery in the baboon. PMID- 2326977 TI - Does ischemic injury augment allograft rejection? PMID- 2326978 TI - Comparison of UW and Collins solution for preservation of the rat heart. PMID- 2326979 TI - Core cooling remains the most effective technique of extended heart-lung (HL) preservation: further experimental evidence. PMID- 2326980 TI - Pulmonary flush preservation decreases polymorphonuclear cell sequestration in the isolated perfused working lung model. PMID- 2326981 TI - Pharmacologic manipulation of elevated pulmonary vascular resistance following 12 hour lung preservation. PMID- 2326982 TI - Allopurinol and deferoxamine improve canine lung preservation. PMID- 2326983 TI - Sensitivity of aerodynamic changes for assessing pulmonary injury in the isolated perfused working lung model. PMID- 2326984 TI - Does organ culture prolong the survival of thyroid allografts in the dog? PMID- 2326985 TI - Immunoalteration of murine thyroid gland in UW solution at hypothermia. PMID- 2326986 TI - International pancreas transplantation registry analysis. PMID- 2326987 TI - Does pancreas transplantation really improve the patient's quality of life? PMID- 2326988 TI - Morbidity during the first year after pancreas transplantation. PMID- 2326990 TI - Management of delayed complications of the duodenal loop in whole organ pancreatic duodenal transplantation. PMID- 2326989 TI - Complications occurring after whole organ duodenopancreatic transplantation: relation to the allograft duodenal segment. PMID- 2326991 TI - Transplantation of two diabetic patients with one divided cadaver donor pancreas. PMID- 2326993 TI - Pancreas revascularization following combined liver and pancreas procurement. PMID- 2326992 TI - Human segmental pancreas transplantation with special reference to vascular thrombosis. PMID- 2326994 TI - The vascular supply in human pancreaticoduodenal grafts: an angiographic study. PMID- 2326995 TI - The first Munich experience with the bladder technique in pancreatic transplantation. PMID- 2326996 TI - Pancreatic transplantation in Lyon: the whole series. PMID- 2326997 TI - Prevention of rejection and fibrosis: considerations in 25 patients. PMID- 2326998 TI - The use of SMS 201-995, a somatostatin analog, in pancreas transplantation. PMID- 2326999 TI - Ultrastructural changes of human pancreatic allografts after cold ischemia and reperfusion. PMID- 2327000 TI - Simultaneous recovery of whole pancreas without arterial reconstruction in the multiple organ liver donor. PMID- 2327001 TI - Initial evaluation of pancreatic cellular subpopulations by fine needle aspiration in clinical pancreas transplantation. PMID- 2327002 TI - Pancreatic retransplants: an analysis of the outcome. PMID- 2327003 TI - Simultaneous pancreas and kidney transplants versus single kidney transplants and previous kidney transplants in uremic patients and single pancreas transplants in nonuremic diabetic patients: comparison of rejection, morbidity, and long-term outcome. PMID- 2327004 TI - Renal transplantation in diabetes mellitus: influence of combined pancreas-kidney transplantation on outcome. PMID- 2327005 TI - Low incidence of rejection following combined kidney and pancreas transplantation. PMID- 2327006 TI - Urinary cytology as a complementary marker of rejection in combined kidney and pancreatic transplants with urinary drainage. PMID- 2327007 TI - Long-term glucose control after pancreatic transplantation. PMID- 2327008 TI - Glucagon-stimulated serum C-peptide levels in the early period following pancreas transplantation. PMID- 2327009 TI - Conversion of whole pancreaticoduodenal transplants from bladder to enteric drainage for metabolic acidosis or dysuria. PMID- 2327010 TI - Metabolic control in recipients of duct-occluded segmental pancreatic grafts: a four-year follow-up. PMID- 2327011 TI - Graft pancreatitis late after pancreatic transplantation. PMID- 2327012 TI - Thrombocytosis following segmental duct-occluded pancreatic transplantation. AB - The average platelet counts in our patients with functioning SPK were significantly higher during postoperative week 2 and the interval of weeks 5 through 9 compared with a matched group of KTA recipients. The thrombocyte values in the SPK group were consistently elevated above the normal range (except postoperative week 1) but less than a platelet level typically requiring therapeutic intervention (greater than 1 mil/mm3). However, because potential pathology both locally (graft pancreatitis, endothelial damage of preservation and operative trauma, diminished graft blood flow) as well as systemically (atherosclerosis, hypertension) is present in SPK patients, we consider them at high risk for thromboembolic complications and therefore support prophylaxis of post-SPK thrombocytosis with platelet inhibitors. PMID- 2327013 TI - Percutaneous pancreas transplant fine needle aspiration and needle core biopsies are useful and safe. PMID- 2327014 TI - Safety and efficacy of cystoscopically directed biopsy in pancreas transplantation. PMID- 2327015 TI - Findings in pancreatic juice cytology compared with histologic findings in the pancreatic graft. PMID- 2327016 TI - Serum anodal trypsinogen is a predictive biochemical marker for pancreas allograft rejection. PMID- 2327017 TI - Prospective histocompatibility testing in pancreas transplantation. PMID- 2327018 TI - DR matching improves cadaveric pancreas transplant results. PMID- 2327019 TI - Course of diabetic retinopathy after pancreas transplantation. PMID- 2327020 TI - Neuropathy and psychosocial adjustment after pancreas transplant in diabetics. PMID- 2327021 TI - Beneficial effect of pancreatic transplantation in insulin-dependent diabetes mellitus patients. PMID- 2327022 TI - Serum pancreatic secretory trypsin inhibitor monitoring for early diagnosis of pancreas allograft rejection in dogs. PMID- 2327023 TI - Histologic features of rejection in cystoscopically directed needle biopsies of pancreatoduodenal allografts in dogs and humans. PMID- 2327024 TI - Improvement of pancreas allograft survival by donor and/or graft pretreatment with CyA and concanavalin A. PMID- 2327025 TI - PGE2 elevation occurs in the urine in both bladder and duodenally drained pancreas allograft rejection. PMID- 2327026 TI - Donor-specific antigen and cyclosporine fail to prolong rat pancreas survival. PMID- 2327027 TI - The effect of histocompatibility matching and cyclosporine on rat pancreas transplants. PMID- 2327028 TI - Elimination of OX8+ cells prolongs cardiac but not pancreatic allograft survival across minor (non-MHC) histocompatibility barriers. PMID- 2327029 TI - An in vitro method of assessing the immunoprotective properties of microcapsule membranes using pancreatic and tumor cell targets. PMID- 2327030 TI - Xenografts of organ-cultured fetal pig pancreas in NOD mice: a comparison with allografts and isografts in transiently immunosuppressed recipients. PMID- 2327031 TI - Nonresponsiveness induced in fetal pancreas allografts by pretreatment with donor spleen cells and anti-CD4 monoclonal antibodies prior to grafting. PMID- 2327032 TI - [Injuries in children under school age. A two-year case-load of a casualty department involving children under 7 years of age]. AB - In order to contribute to current knowledge about injuries in pre-school children, the authors registered a material of 872 children under the age of seven years from a casualty department. 60% of these were boys. The annual incidence of 9% and the age distribution with the maximum for children aged 1-3 years both corresponded to the results of previous investigations. A steep increase in the sex difference could be demonstrated from the age of three years. This increase has not been described previously. The severity of the injuries was independent of the sex and the place of injury but depended upon the nature of the injury and the mechanism of the injury. Falls or jumps to lower levels were conspicuous by causing particularly many severe injuries. Children under the age of one year were particularly often injured by falls while children of one year constituted a high risk group for burns. These mechanisms of injury are obvious subjects for prophylactic measures. PMID- 2327033 TI - [Injuries at day care centers and family day nurseries. A two-year case-load of a casualty department involving children under 7 years of age]. AB - With the object of demonstrating whether injuries in children cared for outside their homes differ from injuries in children as a whole, the authors registered a material of children in the age group 0-6 years from a casualty department. Ninety injuries which had occurred during care outside the home were compared with the remaining 782 injuries. An enormous increase in the proportion of injuries occurring in day care centres and in family day nurseries was observed in contrast to the findings in previous investigations. This can be explained by the increasing number of children cared for outside their homes. 1.7 times as many injuries as were registered were anticipated and it is concluded that care outside the home did not present increased risk for injuries in the children involved. Injuries were most frequent among four-year-olds. Injuries sustained by falls or jumping to lower levels were relatively frequent while injuries caused by crushing, biting, cutting or stabbing were relatively rare and burns were not registered at all. PMID- 2327034 TI - [Neurologic complications in connection with the surgical treatment of 577 cases of carotid artery stenosis]. AB - During the period January 1982 till June 1988, 536 patients underwent 577 carotid thrombendartectomies in the Department of Vascular Surgery RK in the University Hospital in Copenhagen. Preoperatively, 270 patients (47%) had experienced transient ischaemic attacks (TIA), 247 (43%) had experienced stroke (APC) and 19 (3%) had non-focal symptoms while 41 (7%) had asymptomatic stenoses. Postoperatively, 17 (2.9%) patients developed TIA, 22 (3.8%) developed slight neurological symptoms and 40 (7%) had more severe neurological complications and six of these (1%) died. None of the patients died from other causes during the first month. The frequency of complications had no relationship to the preoperative focal symptoms, but in patients with non-focal symptoms this was 37%. The degree of stenosis of the contralateral internal carotid artery (ICA) was correlated positively with the occurrence of severe neurological complications which were observed in 5% without contralateral ICA changes, in 7% with stenoses and in 20% with contralateral ICA occlusion. Patients with cerebral infarction developed complications significantly more frequently (20%) than patients with normal CT scans. The risk was also found to be increased in cases with a high pressure gradient across the stenosis and low pressure peripherally in the occluded artery (stump pressure). Follow-up examination of the 73 patients with complications on average 39 months after operation revealed that 37 patients (6.4%) had severe neurological symptoms resulting either from the operation or subsequent APC; seven patients required complete nursing care (1.2%) and 17 patients died during the period of observation. On follow-up examination, 15 patients had been occupationally active for at least 1.5 years. PMID- 2327035 TI - [Hemoglobin concentration prior to the 20th week of pregnancy correlated with complications in the third trimester]. AB - The haemodynamic changes in pregnancy result in decrease in haemoglobin and haematocrit. It has previously been demonstrated that absence of this decrease or even increase in the haemoglobin concentration (Hb) and haematocrit (Hct) values measured in the third trimester or late in the second trimester can be correlated to increased risk of development of hypertension, pre-eclampsia and intrauterine growth retardation. In the present investigation, the authors have investigated whether the abovementioned complications of pregnancy can also be correlated to high Hb and high Hct measured early in the third trimester. The investigation included 373 healthy pregnant women, 46 of whom had Hb greater than or equal to 8.3 mmol/l in the 13th-19th weeks. Complications of pregnancy occurred in 17.4% of the 46 women. Among the remaining 327 pregnant women with Hb less than 8.3 mmol/l, complications of pregnancy were observed in only 5.8%. This difference is significant. The blood volume increases by approximately 1.5 litre during pregnancy. The plasma volume increases by 50% from the seventh to the 32nd week and thereafter remains constant until delivery. The erythrocyte volume increases first from approximately the 16th week and increases by a total of 25%. The early increase in plasma volume results in a decrease in the haemoglobin concentration (Hb) and in the haematocrit (Hct) value. During the third trimester, Hb and Hct increase again as a result of the increased erythrocyte volume. A positive correlation has been demonstrated between the magnitude of the plasma volume in the third trimester and the birth weight and a negative correlation between Hb in the third trimester and the birth weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327036 TI - [Legionella infections. Diagnostic and therapeutic problems at intensive care units]. AB - Legionnaires' Disease may pose great diagnostic problems in an intensive care setting. The serological diagnosis is often considerably delayed, and, on account of the invasive therapeutic and monitoring procedures employed, the risk of diagnostic errors caused by bacterial contamination (or of genuine superinfection) is high. Therefore, specific antibiotic treatment, instituted on the clinical suspicion of severe legionellosis, should only be discontinued on definite indications (such as severe allergic or toxic reactions to the treatment). Three cases of severe legionellosis are presented to illustrate this. PMID- 2327037 TI - [Treatment of acute chloroquine poisoning]. AB - Acute chloroquine poisoning is life threatening with risk of death from apnoea and cardiac arrhythmia within a few hours of ingestion. Mechanical ventilation, infusion of pressor agents and large doses of diazepam seem to provide effective treatment. This treatment was introduced by Riou et alii (N Engl J Med 1988; 318; 1-6), and we used it successfully in a case of severe chloroquine poisoning. Intensive treatment was given during the first two days of intoxication, when the whole blood chloroquine phosphate concentration was high (more than 10 mumol/kg), corresponding to absorption from the gut and distribution to the organs. Hereafter the whole blood chloroquine phosphate concentration decreased increasingly slowly, probably due to equilibrium with tissue stores. PMID- 2327038 TI - [Near death from the use of playground equipment]. AB - A life-threatening case of accidental strangulation caused by play-ground equipment (in this case a play house) is described. The new standardized recommendation about playground equipment had not been observed. Attention is drawn to this case in order to improve the safety of playground equipment. PMID- 2327039 TI - [The role of the media in health information and prevention]. PMID- 2327040 TI - [District psychiatry in the Naestved region. Consequences of a reorganization]. AB - Community psychiatry was introduced in the Naestved region on 1.1.1987. Anticipating that the number of admissions would be reduced as a result of this, the hospital services were altered: a day ward was inaugurated and a district team was organized and, simultaneously, the total number of psychiatric beds was reduced. In order to investigate the effects of these conversions, the patterns of admission were reviewed retrospectively and compared for the years 1986 and 1987. This investigation revealed that the number of admissions was reduced but that this occurred at the expense of many alcoholics and drug addicts, many of whom have disappeared from the psychiatric therapeutic system. The only group which it proved possible to retain in their own environment consisted of the group of schizophrenics. The question is raised of whether this group gains by this. PMID- 2327041 TI - Estimation of the temperature increase in the focus of a lithotripter for the case of high rate administration. AB - In a recent study Delius et al. demonstrated an increased amount of kidney damage when applying shock waves with a high pulse repetition frequency equal to 100 Hz. The authors interpreted this effect by means in terms of a cavitational mechanism although they could not exclude thermal effects. The present paper estimates the temperature increase for the conditions of the pre-cited study. Taking into account spectral properties of the pressure in the form of cosine, triangle pulses, including their overshoot, as well as an experimental shock wave pulse shape it was possible to compute the temperature increase within the focus of the lithotripter. The maximum estimated temperature increase was equal to 1.8 degrees C for 3000 shock wave pulses of 80 MPa peak pressure. The results of those computations exclude the possibility of significant thermal effects in the damage of kidney tissues even if the administration rate equals 100 shock wave pulses per second. PMID- 2327042 TI - Capacitance hydrophones for pressure determination in lithotripsy. AB - Capacitance hydrophones have been designed and applied for pressure measurements of shock waves in lithotripsy. Their working principle, properties, and design are discussed. Formulae are given, permitting the determination of pressures and calibration of hydrophones from electric measurements. Examples of comparative measurements with electrodynamic and PVDF hydrophones are presented, confirming the correctness of obtained peak pressure values. The hydrophones are characterized by high durability, small controlled nonlinearity, and a wide frequency band. However, they cause distortions in the shape of the overshoot of the measured shock wave pulses and their application is limited to measurements in the focal region. PMID- 2327043 TI - Lysis of cells in Elodea leaves by pulsed and continuous wave ultrasound. AB - Resonance lysis of the cells in the leaves of the aquatic plant Elodea originally reported by Miller have thresholds at intensities of a few W/cm2. With pulsed ultrasound, the resonance behavior vanishes and the thresholds are at much higher amplitudes. This is similar to the characteristics of the thresholds for killing of Drosophila larvae by pulsed ultrasound. Both organisms contain small gas bodies within the tissues which may serve as nuclei for a cavitation related phenomenon. The results suggest that the response of these bubbles to continuous wave fields and very short pulses is qualitatively different. PMID- 2327044 TI - Geographical information systems for studying the epidemiology of cattle diseases caused by Theileria parva. AB - Data on selected variables which influence the epidemiology of cattle diseases caused by Theileria parva were assembled and entered in a computerised geographical information system. Variables studied included the distributions of major hosts (cattle and buffalo), the vector ticks (Rhipicephalus appendiculatus and related species) and the reported presence of East Coast fever, corridor disease and January disease. In addition, the distribution of climatic suitability for R appendiculatus was assessed using the model CLIMEX run on an interpolated climate database developed for Africa. Distribution maps of each variable were produced. The potential value of geographical information systems in studies of disease epidemiology and control is discussed, with examples of how sensitivity may be enhanced by the inclusion of additional variables. In addition, subject areas in which poor data quality and inadequate data standardisation may limit the use of these systems are identified and discussed. PMID- 2327045 TI - Survey of levels of propetamphos and diazinon used to control sheep scab in Northern Ireland. AB - As a result of an increase in the incidence of sheep scab in Northern Ireland, the concentrations of propetamphos and diazinon were measured during 1987 and 1988 in fleece and liquid dip samples from selected flocks, including some in which inadequate dipping was suspected. Sixty-five per cent and 68 per cent of the liquid dip samples contained less than the manufacturer's recommended maintenance concentrations for propetamphos and diazinon respectively. The concentrations found in fleece were also lower than those found in sheep which were dipped with the recommended concentrations of propetamphos and diazinon in a controlled experiment. PMID- 2327046 TI - Hexamitiasis and an emaciation syndrome in pheasant poults: clinical aspects and differential diagnosis. AB - Clinical hexamitiasis was recorded in pheasant poults between six and 12 weeks old, after placing the birds into release pens, and was characterised by reduced appetite, lethargy and emaciation. Post mortem the carcases were dehydrated. The presence in the lumen of the gut of characteristic motile organisms which could often be found several hours after death, provided a good clinical diagnosis. An emaciation syndrome, clinically similar but not associated with hexamitiasis or other pathogens also occurs in poults. It is characterised by extreme emaciation, largely confined to the pectoral muscles, and dehydration although the birds continue to eat and drink; the cause is unknown. Both hexamitiasis and the emaciation syndrome can cause high morbidity and mortality. PMID- 2327047 TI - Gastropathy in young lambs. PMID- 2327048 TI - Animals in nurseries and child-minders' premises. PMID- 2327049 TI - Palatine arterial haemorrhage in a cat. PMID- 2327050 TI - Vaginal probes. PMID- 2327051 TI - Non-specific pruritus in dogs. PMID- 2327052 TI - Dietary factors in mammalian toxicity of chemicals. AB - In addition to the normal nutritional requirements for an adequate diet, protein intake (especially that rich in sulfur amino acids) is required for the synthesis of detoxifying enzymes; glycine and glutathione are required for conjugation reactions. Phospholipids and lipotropes are needed for the synthesis of biological membranes including those of the hepatic endoplasmic reticulum where detoxication of most xenobiotics takes place. Carbohydrates provide metabolic energy and glucuronides for conjugation. Vitamins, such as ascorbic acid, tocopherol and retinoids and required as antioxidants and for free radical removal. Iron is needed in heme protein synthesis and in the synthesis of the synthesis of the drug metabolising cytochrome P450 enzymes. Adequate nutrition is important in reducing mammalian susceptibility to the toxic effects of foreign chemicals. PMID- 2327053 TI - Caterpillar envenomations: a prospective study of 112 cases. AB - A 1-year prospective study was conducted to identify epidemiological factors associated with caterpillar envenomations. Of 117 envenomations, 112 were included in the study. Identification of the caterpillars involved was accomplished in 68% of the cases. Six caterpillar species were identified, 4 of which [Hemileuca maia (Drury), Automeris io (F), Megalopyge opercularis (JE Smith)/Lagoa crispata (Packard) and Sibine stimulea (Clemens)] were properly implicated in envenomations. Clinical effects most commonly reported were local pain, erythema and swelling in 96%, 89% and 72% of patients, respectively. Atypical responses including muscle spasms, paresthesia and radiating pain to an extremity were noted in 26% of patients. Sixteen percent of patients had a history of allergy, but no patient in this subgroup exhibited a "hive-like" dermatologic or anaphylactic allergic response. No positive correlation could be drawn between allergy history and extent of clinical effect following envenomation. Mild to moderate local response following envenomation was typical. However, 61% of patients evaluated experienced mild to moderate effects at least 24 h post-envenomation. PMID- 2327054 TI - Cholinergic, anticholinergic agents and ethanol interaction. AB - The effect of cholinergics and an anticholinergic agent on hepatic ethanol metabolizing enzymes was studied. Short-term administration of the cholinomimetic arecoline or the anticholinergic scopolamine induced rat liver mitochondrial aldehyde dehydrogenase (L-ALDH) isoenzyme with the apparent high and low Km, respectively. In addition, scopolamine inhibited cytoplasmic L-ALDH. This suggests differential sensitivity of the L-ALDH isoenzymes to these agents. Scopolamine and the cholinomimetic pilocarpine enhanced rat and mouse liver alcohol dehydrogenase (L-ADH) in vitro, respectively. This indicates species dependent effect of these agents on L-ADH. The results suggest interaction of the cholinergic system with ethanol metabolizing enzymes which may contribute to the peripheral action of alcohol. PMID- 2327055 TI - Reports from the 1989 AACT/AAPCC/ABMT/CAPCC scientific meeting. 11-15 October 1989, Atlanta, Georgia. PMID- 2327056 TI - Amphotericin B overdoses in infants: is there a role for exchange transfusion? PMID- 2327057 TI - Papaverine, tetrahydropapaverine and ethanol metabolizing enzymes. AB - The effects of tetrahydropapaverine (THP) and papaverine (PAP), an O-methylated analogue, on rat liver alcohol dehydrogenase (L-ADH) and aldehyde-dehydrogenase (L-ALDH) were studied in vitro. The action of THP on these enzymes was also evaluated in vivo in conjunction with its effect on voluntary intake of ethanol by the rat. Both L-ADH and mitochondrial L-ALDH were inhibited in vitro in the presence of 10(-4) M THP. Conversely, stimulation of L-ADH and L-ALDH occurred by PAP in the concentration range between 10(-4) to 10(-6) M in vitro. Acute or daily administration of THP for five consecutive days did not alter voluntary intake of ET by the rat or changed specific activity of these hepatic enzymes in vivo. The structure activity of these compounds in relationship to the enzymes studied suggest the importance of O-methylation on the enzymatic effect studied which may possibly underlie some of the hypothesized action of THP on libation of alcohol. PMID- 2327058 TI - An outreach program to low-income, high risk populations through WIC. AB - Through a special New York State legislative grant, we were able to produce brochures in Spanish and Haitian French, and to train WIC Staff, Public Health Nurses and Healthy Neighborhood staff in poison prevention. This study involved all the WIC sites in our seven county region, who reach a population of over 10,000 families who have been identified as low income, high-risk individuals in a survey conducted by the American Red Cross. Pre-test showed that the staff knew of the Poison Center but had not instructed clients in poison prevention. Post testing of WIC staff showed a significant increase in knowledge about poison prevention and increase in the frequency of client instruction. The main thrust of this program was to assure that the phone number of the Poison Center was prominently posted in each home and that clients knew that the Poison Center was available 24 h every day in a poison emergency. PMID- 2327059 TI - Skeletal muscle relaxant ingestion. AB - We retrospectively analyzed 56 consecutive cases involving acute skeletal muscle relaxant exposure that were reported to the Poison Control Center over a 1-year period. The age range was 9 mo to 56 years (mean 18.9 +/- 13.1) with the site of exposure being the primary residence in 54 cases (96.4%). The reasons for inquiry to the Poison Center were reported to be intentional suicide in 26 cases (46.4%), accidental in 21 cases (37.5%), with intentional misuses in 5 cases (8.9%). No deaths were reported. Eighteen cases (32.1%) were reported with co-ingestants (average number of substances taken was 2.7 +/- 0.8). Of these cases 3 patients (16.7%) had major effects with life-threatening symptoms with 6 (33.3%) patients having no symptoms. Of the remaining 38 cases, 17 (44.7%) wer cyclobenzaprine, 6 (15.8%) were methocarbamol, 5 (13.2%) were carisoprodol, 5 (13.2%) were chlorzoxazone, 3 (7.89%) were Baclofen and the remainder were either life threatening symptoms (2.6%), while 29 (74.3%) had no or minor effects with symptoms that subsided. We conclude that morbidity and mortality are low in pure skeletal muscle relaxant ingestion, however it may be increased in multiple ingestions. PMID- 2327060 TI - Formate levels following a formalin ingestion. AB - Although formalin ingestions have previously been reported in the literature, technology has only recently been developed to measure both formaldehyde and formate levels in plasma. Methanol, formaldehyde, and formate levels were followed in the case reported here until the patient's death approximately 13 h after the ingestion. The clinical course was marked by an initial profound CNS depression followed by an apparent clinically quiescent period. Severe abdominal pain and retching preceded the development of seizures, DIC, severe hypotension, and cardiac arrest. Methanol levels rose throughout this 13-h course. Formate and formaldehyde levels increased until bicarbonate and ethanol therapy were instituted. The "fixing" of the stomach by formaldehyde may have produced delayed absorption following formalin ingestion. Therapeutic implications are discussed. PMID- 2327061 TI - Physical change, time of day, and child characteristics as factors in poison injury. AB - In a study of 85 children under 6 y whose mothers called the poison center, information regarding the physical surroundings of the substance ingested at the time of the incident was obtained along with ratings of maternal stress and child behavior problems. In 51% of the incidents, the substance had recently been moved from a usual storage site or was in use at the time of the ingestion. Environmental changes occurred in 1/3 of those poisoned between 4 and 6 pm which was the 2-h period of the greatest incidence. Poisoning in children 1 and 2 y were more likely to have followed physical environmental change. Children with higher child behavior problem score were more likely to be poisoned in the morning. PMID- 2327062 TI - Paperless Poison Center: an alternative to bubbling. AB - The Paperless Poison Center (PPC) is a computer software program which allows for direct entering of data collection, data submission to the American Association of Poison Control Centers (AAPCC) and on-site analysis of data using RBASE. A comparison of the computer collection system vs bubbling of AAPCC sheets is discussed as to speed and ease of use, accuracy and cost. A summary of our comparison concludes that the computerized system is cost effective, more efficient, and more accurate than the paper method. Poison Information Specialist (PIS) acceptance of the program has been overwhelmingly positive. PMID- 2327063 TI - Self-scheduling: a unique staffing approach for a regional poison information center. AB - For optimal effectiveness, a regional poison information center (RPIC) must be operational 24 h daily, every day of the year. While the formula to calculate the number of full-time equivalents (FTE'S) needed to staff a shift at an RPIC is well known, the best method for successful estimation rotation of an RPIC's professional staff to attain adequate 24-h coverage remains a conundrum. For a 12 mo period, full and part-time Poison Information Specialists at an RPIC self scheduled all of their work time. Each Specialist rotated 2 shifts (days/nights) or chose a steady off-shift (evenings or nights). On a rotation basis, a Poison Information Specialist schedule coordinator was assigned to "balance" each 4-week period of self-scheduled time. This eliminated inadequate staffing on any given shift. Self-scheduling of work time has impacted positively on staff morale, since it commits the ownership of scheduling to those directly affected by the outcome. Costly illness time has decreased by 23 d/y and administrative staff are able to expand the 10 h, once spent in developing weekly staff schedules, in other areas of productivity. PMID- 2327064 TI - Plasma catecholamine activity in chronic lead poisoning. AB - Plasma catecholamines where measured in 15 children with chronic lead poisoning and 15 matched controls by radioimmunassay. The data suggest that plasma catecholamines (norepinephrine and epinphrine) were significantly elevated in chronic lead poisoning. Plasma catecholamine elevation may well be important in the clinical finding of hyperactivity and hypertension associated with chronic lead poisoning. PMID- 2327065 TI - Fluoxetine ingestion: a one year retrospective study. AB - Fluoxetine (PROZAC) is a recently marketed straight chain antidepressant unrelated to the cyclic anti-depressants. There is only limited information on fluoxetine and a single case report on overdose (benign outcome) in the literature. In response to this we performed a 1y retrospective chart review at 2 AAPCC certified poison centers. Forty-four exposures to fluoxetine were reviewed from 1988; 31 cases were treated in a HCF, 2 cases were followed at home by phone and 11 cases were lost to follow up. Thirteen cases with follow up (FU) reported no coingestants; 3 cases reported increased anxiety without cardiovascular (CV) changes, 2 cases presented confused with out CV changes, and 8 cases were asymptomatic. Eight cases with FU had ETOH and/or benzodiazepines as a coingestant and experienced only a decreased level of consciousness that could be explained by the coingestant. Five cases remained asymptomatic with reported coingestants of APAP #3, lorazepam, haloperidol, molindone, alprazolam, propranolol, phenobarbital (level 18.2). Four cases were excluded from the evaluation due to the coingestants involved. No seizures were recorded in this series. Three possible drug reactions occurred; 2 cases had reactions with tranylcypromine (PARNATE), and 1 case with a diagnosis of septicemia had a severe hyperthermic reaction with therapeutic coingestants of mephytoin, verapamil, digoxin and indocin. We believe overdose with fluoxetine present minimal risk of serious cardiovascular or neurological complications. PMID- 2327066 TI - Treated vs reported toxic exposures: discrepancies between a poison control center and a member hospital. AB - Statistics accumulated by Poison Control Centers (PCC) are routinely used on the local, regional and national levels by governmental agencies to set policy and direct funding. Incomplete reporting by member hospitals is recognized by PCC as a factor contributing to discrepancies in epidemiological estimates; however little emphasis is classically placed by the PCC on expanding reporting from member hospitals. A 1y retrospective review of patients with toxic exposure presenting to an urban Emergency Medicine Department (EMD) was performed to quantify the lack of concordance between treated and reported toxic exposures. 470 toxic exposures presented over the study period, of which only 123 (26%) were relayed to the regional PCC. Inhalation exposures were least likely to be referred for PCC consultation (3%); whereas PCC consultation was obtained for 33% venomous snake bite cases, and 95% of the cyclic antidepressant ingestions. Clusters of similar exposures resulted in fewer PCC consultations. Understanding each hospital's "profile" for handling toxic exposures, and individualized advertisement by the PCC to their member hospital may increase their data reporting. The statistical significance of their epidemiological studies as well as their revenue may increase. PMID- 2327067 TI - Methodological issues in studying the effect of the new oral chelator 1,2 dimethyl-3-hydroxypyrid-4-one (L1) on absorption of iron. AB - Although deferoxamine is currently the drug of choice for iron chelation, there is more and more evidence of its toxicity. As a replacement for deferoxamine, 1,2 dimethyl-3-hydroxypyrid-4-one (L1), a new oral iron chelator, is undergoing clinical studies in thalassemic patients. Iron handling in experimental acute iron intoxication is being studied in a multiphase study. Preliminary results suggest that the L1-iron complex is not absorbed from the gastrointestinal tract. Methodological issues in studying iron chelation in the context of acute iron intoxication are presented. PMID- 2327068 TI - Cinnamon oil abuse by adolescents. AB - Reports in the literature about cinnamon oil toxicity are limited to allergic reactions and local irritant effects from dermatologic exposure. Cinnamon oil is easily obtained from pharmacies in 5-10 ml amounts for use as a flavoring agent and in craft items. Within a 5-mo period the Pittsburgh Poison Center (PPC) documented 32 cases of cinnamon oil abuse; all cases involved males aged 11-16 y and were reported to the PPC by school nurses. Sucking on toothpicks or fingers which had been dipped in cinnamon oil was the primary method of abuse. A rush or sensation of warmth, facial flushing, and oral burning were the experiences reported by the users. Some children complained of nausea or abdominal pain but no systemic effects were reported. Eight patients with dermal exposure had irritation ranging from erythema to welts, which resolved after thorough soap and water decontamination. Two ocular exposures resulted in mild irritation and were successfully treated with irrigation or dilution. The recent popularity of cinnamon oil abuse appears to be related to the ease with which it can be carried, engendering little fear of discovery or chastisement. Despite the relatively low toxicity of cinnamon oil, medical professionals should be aware of its potential for misuse. PMID- 2327069 TI - Prospective evaluation of "crack-vial" ingestions. AB - The "crack" (cocaine alkaloid) epidemic has resulted in an increasing number of hospitalizations of "crack-vial body-stuffers," or patients who ingest "crack vials" in an attempt to avoid prosecution. Management strategies for this type of ingestion are lacking because of the paucity of data. This report discusses the demographics and symptomatology of 23 patients with "crack-vial" ingestions, as well as the value of abdominal radiographs and the utility of varied strategies for decontamination in this patient population. PMID- 2327070 TI - Locoism in horses. PMID- 2327071 TI - Cold-adapted vaccine strains of influenza A virus act as dominant negative mutants in mixed infections with wild-type influenza A virus. AB - The cold-adapted reassortant of influenza A, which is a candidate live virus vaccine, interfered with the replication of parental wild-type virus in mixed infections of either MDCK cells or embryonated eggs. The interference occurred at either the permissive or nonpermissive temperature for the cold-adapted virus. In doubly infected cells, the yield of the wild-type virus was reduced by as much as 3000-fold and the protein synthesis phenotype expressed was that of the cold adapted virus. The interference was detected even when infection with wild-type virus was carried out at a 9-fold excess or 2 hr before infection with the cold adapted virus. As well as interfering with its wild-type parental virus, the cold adapted virus also inhibited the replication of a heterologous influenza A subtype. In addition to its immunogenic potential, the ability to interfere with the replication of wild-type viruses is a desirable trait for any live, attenuated virus vaccine. PMID- 2327072 TI - Intracellular stability of the gene encoding influenza virus haemagglutinin. AB - The intracellular stability of the genome of noninfectious uv-irradiated influenza virus (A/WSN:H1N1) in dividing MDCK cells was investigated using marker rescue techniques. The haemagglutinin gene could still be rescued by infection with A/X49 (H3N2) at 5 weeks postinoculation; its half-life was 13 days. PMID- 2327073 TI - Identification and sequencing of the spheroidin gene of Choristoneura biennis entomopoxvirus. AB - Entomopoxviruses are a class of insect viruses whose virions are embedded in cytoplasmic occlusion bodies. The major component of these protective complexes is a protein called spheroidin. An open reading frame encoding the spheroidin gene of Choristoneura biennis entomopoxvirus has been identified and sequenced in our laboratory. This protein coding region is 1023 nucleotides long and specifies a polypeptide of 38,500 Da. Spheroidin was purified by SDS polyacrylamide gel electrophoresis, electroeluted, and its amino terminus sequence was determined on a gas phase sequencer. We observed that the first 20 N-terminal amino acids were absent in the mature processed form of the spheroidin molecule. Examination of these 20 residues revealed their hydrophobic nature and close resemblance to the consensus signal peptide sequence which is commonly found on membrane proteins. The DNA sequence of the spheroidin gene predicted a processed polypeptide with a molecular weight of 36 kDa. However, spheroidin was observed to aggregate in complexes composed of 50-kDa monomers. Intermolecular disulfide bonds were shown to play major roles in the formation and structure of these viral occlusion bodies. The difference in molecular weight between the predicted protein and its counterpart in infected cells is likely due to post-translational modifications. Indeed, two potential asparagine-linked glycosylation sites are present on the spheroidin molecule. The 5' flanking regions of the spheroidin gene and the vaccinia major core protein precursor gene P4b were shown to share substantial homology. PMID- 2327074 TI - Mapping and sequence of the gene coding for protein p72, the major capsid protein of African swine fever virus. AB - The gene encoding protein p72, the major structural protein of African swine fever virus and one of the most immunogenic proteins in natural infection has been mapped and sequenced. The gene was mapped by using oligonucleotide probes deduced from amino acid sequences of tryptic peptides obtained from purified protein p72. This allowed the location of the gene in fragment EcoRI B of African swine fever virus DNA. The nucleotide sequence obtained from this region revealed an open reading frame encoding 646 amino acids corresponding to a protein with a calculated molecular weight of 73,096 Da. This open reading frame contains the coding information for all the sequenced tryptic peptides from protein p72. A search at the National Biomedical Research Foundation Data Bank did not reveal any significant homology with other described proteins. PMID- 2327075 TI - The sim gene of Escherichia coli phage P1: nucleotide sequence and purification of the processed protein. AB - The sim gene of bacteriophage P1 causes exclusion of a superinfecting P1 phage. We determined the nucleotide sequence of a 1.9-kb DNA fragment that, in plasmids, causes Sim phenotype. There are two open reading frames within this region for proteins of 82 and 259 amino acids. A 1.3-kb fragment containing the larger open reading frame was inserted into an expression vector. Induced cells carrying the hybrid plasmid, termed pBD5, were not infected by phage P1 and produced a 24-kDa protein and, to a smaller extent, a 25-kDa protein. The 24-kDa protein was purified. Comparison of its amino-terminal amino acid sequence with the nucleotide sequence indicated that it is processed from a precursor protein by removal of a hydrophobic leader peptide of 20 amino acids. In vivo processing depends on secA gene function and is necessary for Sim interference with P1 infection. The data are discussed with respect to the function of the sim gene in superinfection exclusion. PMID- 2327076 TI - Coding strategy of the S RNA segment of Dugbe virus (Nairovirus; Bunyaviridae). AB - The S RNA segment of Dugbe (DUG) virus (Nairovirus; Bunyaviridae) was sequenced from three overlapping cDNA clones and by primer extension. The S RNA is 1712 nucleotides in length and contains one large open reading frame (ORF) of 1326 nucleotides coding for a 49.4-kDa protein on viral complementary (vc) RNA. This protein in size corresponds to the DUG nucleocapsid (N) protein (P. Cash, 1985, J. Gen. Virol. 66, 141-148). The 49.4-kDa product was expressed as a fusion protein with beta-galactosidase in Escherichia coli cells and confirmed as DUG N protein by Western blotting with DUG N-specific monoclonal antibody. An additional ORF of 150 nucleotides coding for a possible 5.9-kDa protein is present in the +1 reading frame, 3' to the N protein ORF on vcRNA. DUG S segment mRNA was found to be essentially full length. No evidence was obtained for the existence of a smaller mRNA species that could code for a 5.9-kDa protein. Comparisons of the DUG S RNA sequence and predicted N protein amino acid sequence, with the respective sequences of snowshoe hare, La Crosse (bunyaviruses), Punta Toro, Sandfly fever Sicilian (phleboviruses), and Hantaan (hantavirus) viruses, failed to detect any sequence similarity, although the genomic structure of DUG S RNA is similar to that of the S RNA segment of Hantaan (HTN) virus. PMID- 2327077 TI - Complement-mediated antibody-dependent enhancement of HIV-1 infection requires CD4 and complement receptors. AB - In this study it is demonstrated that complement-mediated antibody-dependent enhancement (C'-ADE) of HIV-1 infection in vitro is blocked by murine monoclonal antibodies to CD4 and complement receptor type 2 (CR2) while HIV-1 infection in the absence of C'-ADE is blocked by anti-CD4 but not anti-CR2 monoclonal antibodies. The anti-CR2 murine monoclonal antibody, OKB7, blocked C'-ADE of HIV 1 infection at concentrations greater than 1 microgram/ml. The anti-CD4 monoclonal antibody, OKT4a, but not OKT4f blocked C'-ADE at concentrations greater than 0.06 microgram/ml. HIV-1 infections were quantitated by cytopathic effect, indirect immunofluorescence, and reverse transcriptase release. It appears from these in vitro studies that C'-ADE of HIV-1 infection requires both CD4 and complement receptors while HIV-1 infection in the absence of antibody and complement requires only CD4. PMID- 2327078 TI - [Is the practice of internal medicine changing?]. PMID- 2327079 TI - [Noninvasive monitoring of the hemodynamic importance of the left atrium]. AB - The authors examined 112 subjects free from cardiac disease, with essential hypertension and myocardial infarction. In all subjects a 12-lead ECG at rest was made as well as a polycardiographic and echocardiographic examination. The authors found that in the group of healthy subjects there is a direct significant linear correlation between the size of the systole of the left atrium and age. The size of the left atrium and the atrial filling fraction were significantly smaller in healthy subjects than in subjects with hypertension and myocardial infarction. The authors draw attention to the necessity to re-evaluate the accepted norm of left atrial size in patients with hypertension and myocardial infarction. The authors found that between the magnitude of the systole of the left atrium and the ejection fraction of the left ventricle a significant relationship of parabolic shape exists. The mentioned correlations suggest that with deterioration of left ventricular function the ratio of the left atrial systole increases up to a certain extent (40% of the ejection fraction); after this borderline is exceeded, the haemodynamic contribution of the left atrium declines again till it is insignificant. PTF-V1 on the ECG which is generally considered a sign of an enlarged atrium reflects in the group of patients with acute myocardial infarction above all the degree of reduction of systolic and diastolic left ventricular function and not changes in the size and function of the left atrium. PMID- 2327080 TI - [Long-term monitoring of changes in contractility of the left ventricular wall in patients with myocardial infarct]. AB - Using two-dimensional echocardiography, the authors made a one-year investigation of left ventricular function in a group of patients after a first transmural myocardial infarction. They evaluated subjectively and quantitatively changes in the contractility and the development of the diastolic area of the left ventricle. They revealed a certain improvement of the contractility, probably as a result of the development of a collateral circulation and altered structure of the infarction focus associated with dilatation of the left ventricle by the Frank-Starling mechanism. PMID- 2327081 TI - [Atypical ventricular tachycardia and atrioventricular blockade]. AB - The authors submit a clinical and electrocardiographic analysis of five patients with atypical ventricular tachycardia with atrioventricular block of an advanced degree. The incidence is relatively rare--cca 1% patients with atrioventricular block are threatened by this type of tachycardia. In these patients there are always reduced serum potassium levels and a longer QT interval, as compared with patients without tachycardia. In two instances there was an association with the use of drugs (Furosemide and Thioridazine) and these patients developed tachycardia even during permanent pacing. Correction of the internal environment and discontinuation of drugs proved therefore decisive, as permanent pacing alone did not always suffice to prevent tachycardia. Without medication atypical ventricular tachycardia develops, in the author's opinion, most probably when bradycardia has persisted for a prolonged period. PMID- 2327082 TI - [Experience with ablation of the bundle of His using electrical discharge]. AB - Ablation of the bundle of His by an electric discharge was made in 10 patients (average age 64 years, range 48-80) unsuccessfully treated with 3-14 antiarrhythmic drugs or their combinations (average 8.7) on account of supraventricular tachycardia occurring repeatedly for 3-44 years (average 12.5 years). By means of a bipolar electrode inserted into the area of the bundle of His a nonsynchronized defibrillation discharge with a mean energy of 323 J (40 380) was administered. On average 2.9 discharges were used (1-9) per patient, in 1-3 sessions. The patients were followed up for a period of 15.3 months (10-19). Permanent complete a-v block was achieved in 6 patients, the remaining 4 patients are also free from complaints with have antiarrhythmic treatment. To all patients a pacemaker was implanted, four times "physiological" stimulation was used. One month after the operation the authors observed once the development of a transient phatic disorder and once the slow development of cardiac tamponade in conjunction with anticoagulant treatment, resolved by pericardial puncture. Ablation of the bundle of His by a defibrillation discharge is thus in carefully selected patients a highly effective method of treatment of stubborn supraventricular tachycardias. PMID- 2327083 TI - [Electrophysiologic effects of orally administered amiodarone]. AB - The authors made an invasive electrophysiological examination of the heart before and after administration of amiodarone by the oral route in 18 patients (15 men and 3 women). Amiodarone was administered in maintenance doses of 200 or 400 mg/day for 3 to 13 months (mean 4.7 months). Comparison of values revealed a significant protraction of R-R, P-Q and QRS intervals on the surface ECG. A-H and H-V intervals on the electrogram of the bundle of His as well as effective refractory periods of the ventricular myocardium were significantly protracted. During high-frequency stimulation of the atria the frequency at which an a-v block grade II type I develops declined. No significant changes developed in Q-Tc intervals on the surface ECG, the PA-A on the electrogram of the bundle of His and in the corrected recovery period of the s-a node. PMID- 2327084 TI - [Somatometric characteristics of patients with hypertrophic cardiomyopathies]. AB - The authors evaluated anthropometric data from 43 men and 17 women aged 20-45 years suffering hypertrophic cardiomyopathy. The affected individuals had a higher body weight associated with larger circumferences of trunk and arms, but smaller circumferences of the lower extremities. The deviations could be due to a lower physical activity of the patients and consistent with this, they were recorded only in the subgroup of patients with subjective complaints. Contrary to these findings, after classification of the patients according to the extent of myocardial hypertrophy, higher body weight was found only in patients with mild affection. The difference could be suggestive of a higher mortality of patients with a more severe affection, accompanied simultaneously by overweight or obesity. Of the dimensions of head and face was enlarged only the head circumference in men. The authors recommend to follow-up the height-weight proportionality of patients. PMID- 2327085 TI - [Acute hemodynamic changes after nifedipine in older men with essential hypertension]. AB - The authors selected from a group of 40 hypertonic patients 9 men (mean age 67 years, range 60-73 years) with reliably evaluated echocardiographic tracings without valvular defects and without impaired left ventricular kinetics. After two weeks on placebo every patients was given a single dose of 20 mg nifedipine. The echocardiographic examination, concurrently with a blood pressure reading, was made at the end of the placebo interval and 2.5 and 7 hours after nifedipine administration. As compared with placebo, nifedipine significantly reduced at each time intervals the end systolic stress of the wall and the blood pressure without accelerating the pulse rate. A significant reduction of the total vascular resistance and increased velocity of the circumferential fibre shortening occurred during the 2nd and 5th hour; the pulse pressure was diminished 5 and 7 hours after nifedipine administration. The favourable haemodynamic action of nifedipine after a single dose confirms the advantage of the preparation in elderly hypertensive patients. PMID- 2327086 TI - [The effect of quinidine on digoxin plasma levels after discontinuation of digoxin therapy]. AB - The authors submit a report on the effect of quinidine on plasma digoxin. The investigation was made in 20 patients wit supraventricular dysrhythmia. After initial digoxin treatment they proceeded with quinidine six hours after the last digoxin dose. Although they did not administer digoxin, the digoxin level increased during quinidine treatment in the course of 12 hours from 2.4 +/- 1.6 ng/ml to 3.8 +/- 12.4 ng/ml. The authors draw attention to the importance of following up digoxin levels in the mentioned drug combination which is supposed to prevent serious complication caused by possible digoxin intoxication. PMID- 2327087 TI - [Diagnosis of lung injury due to amiodarone--contribution of bronchoalveolar lavage]. AB - Based on the authors' own observation of a patient with pulmonary affection during amiodarone treatment, they demonstrate contemporary possibilities of early diagnosis of this potentially serious condition. They emphasize the importance of bronchoalveolar lavage, a non-invasive diagnostic method which provides information on the conditions in the peripheral portions of the lungs. The authors give an account of data in the literature on the pathogenesis of side effects of amiodarone in the lungs and draw attention to the need of systematic pneumological check-up examinations during treatment. If the drug is discontinued in time, all side-effects may recede spontaneously. PMID- 2327088 TI - [Plasmocellular leukemia with IgD paraproteinemia]. AB - The authors describe the case of an 80-year-old woman with a plasmocytoma IgD lambda, which developed into plasmocellular leukaemia. The laboratory finding reminded at first of chronic lymphatic leukaemia. The correct diagnosis was assisted by marked leucocytosis with the release of a major number of plasmatic cells into the peripheral blood stream. The finding was confirmed on the basis of sternal puncture, cytochemical examination, immunochemical examination of the blood and urine and X-ray of the skull. Treatment led to marked clinical and laboratory improvement. The patient died, however, from pneumonia three months after establishment of the diagnosis. Post-mortem examination revealed an extensive infiltration of many organs and a myelomatous kidney. The authors present some differential diagnostic reflections on plasmocellular leukaemia. PMID- 2327089 TI - [Use of monoclonal antibodies in HLA immunology]. AB - The author gives an account of the classification and use of HLA monoclonal antibodies. In experimental work the author demonstrates the contribution of investigations of the expressivity of histocompatible antigens class I and II and their changes in sound and tumourous tissues. In clinical practice they are important in particular in transplantology--cleaning of bone marrow, follow up of the GvH reaction, monitoring of patients. HLA monoclonal antibodies serve to reveal the polymorphism in the HLA sphere and the follow up of general biological laws. PMID- 2327090 TI - Breast cancer in situ: a retrospective review of 23 cases with a minimum of 10 year followup. AB - Twenty-three cases of breast carcinoma in situ (12 with intraductal carcinoma and 11 with lobular carcinoma in situ) seen at Charleston Area Medical Center between 1957 and 1977 were reviewed. The mean age diagnosis was 50 years (age range: 30 86 years). An asymptomatic breast mass was the initial symptom in 19 patients (82 per cent). Mammography, performed in seven patients, was abnormal in five. A simple or modified radical mastectomy was performed in 20 women and wedge resection in three. Twenty-two women underwent ipsilateral axillary nodal dissection, and all but one had histologically-negative nodes. Only one patient in this series died with metastatic breast cancer. Six other patients died from non-malignant causes. Sixteen patients are still alive with no evidence of disease from 11.5 to 26.5 years after the initial diagnosis. The role of simple excision with or without radiotherapy in breast carcinoma in situ remains to be determined. PMID- 2327091 TI - Role of thrombolytic therapy in axillary-subclavian vein thrombosis. AB - Axillary-subclavian vein thrombosis in young patients has produced long-term disability because of failure of the thrombosed vein to recanalize. In a review of 10 patients with axillary-subclavian vein thrombosis treated in our institution, four were effort vein thrombosis. All patients were diagnosed by venography. One patient received urokinase with complete resolution of symptoms and complete dissolution of the clot after two days of initial therapy, which was confirmed by venography and duplex imaging. Another patient received streptokinase with partial resolution of symptoms and dissolution of the clot, which was confirmed by venography. The other two patients were treated with conventional anticoagulant therapy with partial resolution of symptoms and no dissolution of the clot. Thrombolytic therapy appears to be superior to anticoagulation in dissolution of symptoms in effort vein thrombosis and should be considered in its management if the diagnosis is made early. PMID- 2327092 TI - Diagnostic and therapeutic subsets in the management of urinary tract infection. AB - Urinary tract infections are common and easily treated, but studies from the last decade have identified important diagnostic subsets that have led to cost effective therapy based upon rational scientific data. Management of urinary tract infections (UTI) in the immunocompromised, the elderly and young women is addressed. Short-course antibiotic therapy and use of intravenous pyelography in young women with UTI are discussed. PMID- 2327093 TI - Intraabdominal infections. PMID- 2327094 TI - Intraabdominal infections--introduction. PMID- 2327095 TI - Fecal peritonitis: microbial adherence to serosal mesothelium and resistance to peritoneal lavage. AB - Fecal contamination of the peritoneal cavity is a serious and potentially life threatening event. While numerous models have been developed to study the pathogenesis of intraabdominal infection, to date, most investigations have failed to focus on the adherence of the contaminants to the serosal mesothelium. In the present investigation, the cecal ligation and puncture technique (CLP) was performed in Sprague-Dawley rats to study the following: (a) the kinetics of microbial adherence to the serosal mesothelium, (b) the stability of the aerobic and anaerobic intraperitoneal/mesothelial populations, following extended saline lavage, and (c) the impact of antimicrobial lavage on the stability of the mesothelial microbial populations. The Enterobacteriaceae rapidly colonized the serosal mesothelium and were the predominant flora up to 4 hours post-CLP. After 8 hours, the Bacteroides fragilis group represented the predominant peritoneal wash and mesothelial-associated microorganisms. Extended saline lavage failed to significantly reduce the mesothelial microbial populations. While antimicrobial lavage produced an immediate decrease in mesothelial microbial recovery, the results were transitory and the microbial populations achieved or exceeded prelavage levels at 24 hours postlavage. Microbial colonization of the peritoneal mesothelial surface is a rapid and stable phenomena following penetrating injury to the distal bowel. The results further suggest that the mesothelial populations are resistant to intraperitoneal lavage. PMID- 2327096 TI - Percutaneous control of a portacaval H-graft: description of a new device and its initial clinical application. AB - A percutaneously-controlled inflatable cuff which can change the diameter of a portacaval H-graft has been developed and used in 10 patients. When inflated, the cuff narrows the H-graft to increase portal pressure and reduce shunting. Use of the cuff has been of clinical significance in 3 of 7 long-term surviving patients. Narrowing the shunt improved the clinical state in 2 patients with encephalopathy, and reopening a closed shunt improved ascites in the third patient. Duplex ultrasound and deep Doppler have demonstrated an alteration of hepatic portal blood flow following inflation of the cuff after 6 months. It is concluded that further development of this controlled portacaval H-graft is warranted. PMID- 2327097 TI - Herniorrhaphy and concomitant peritoneovenous shunting in cirrhotic patients with umbilical hernia. AB - From 1981 to 1987, a total of 40 cirrhotic patients with umbilical hernia were treated either by conventional herniorrhaphy (26) or by herniorrhaphy and concomitant insertion of a peritoneovenous (PV) shunt (14). The aim of concomitant PV shunt insertion was to reduce postoperative complications of herniorrhaphy in those patients with intractable ascites, or in whom difficulty to control postoperative ascites was contemplated. In the group of patients with PV shunt, 8 were class B and 6 were class C according to Child's classification; 7 patients had complicated hernia including 2 patients with skin ulceration, 4 with rupture, and 1 with incarceration. In the group with standard herniorrhaphy, 5 patients were class A and 21 were class B; 13 patients were operated on electively for uncomplicated hernia without ascites, 6 had incarceration, and 7 had skin ulceration. The technical procedure of concomitant PV shunting and hernia repair included: insertion of the valve, surgical repair of the hernia, and insertion of the venous tube. In that order, in-hospital mortality was nil. Postoperative complications included sepsis in 2 patients who had concomitant insertion of a PV shunt, and massive ascitic fluid production in 5 patients treated by conventional herniorrhaphy, resulting in ascitic leak from the surgical wound in 1 case. Recurrence of the hernia was observed in 6 patients treated by conventional herniorrhaphy, and in none who had a patent PV shunt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327098 TI - Evaluation of hemodynamics and hepatic mitochondrial function on extrahepatic portal obstruction in the rat. AB - An animal model resembling clinical cases with extrahepatic portal vein obstruction was developed. The changes in hepatic mitochondrial function and the hepatic hemodynamics including hepatic regional blood flow, portal venous pressure, and portogram were evaluated to assess the effect of portal vein obstruction in the model. Portal vein ligation in this model was a simple and easy maneuver and could produce collateral veins to the liver--cavernomatous transformation--which were obviously seen in clinical patients with extrahepatic portal obstruction. Hepatic blood flow was significantly decreased until 5 days after portal vein ligation; however, hepatic blood flow was gradually increased and reached the normal value at 3 weeks after portal vein ligation due to the formation of the collateral veins to the liver. Respiratory parameters of mitochondria were gradually decreased and reached the lowest levels at 5 days after portal vein ligation, while they recovered to normal values in accordance with increasing hepatic blood flow at 3 weeks after portal vein ligation. In extrahepatic portal obstruction, although the liver is temporarily deteriorated by portal vein obstruction such as portal vein thrombosis, hepatic blood flow and the liver functions are to be normally improved with the formation of collateral veins to the liver. PMID- 2327099 TI - Six-year results of annual colonoscopy after resection of colorectal cancer. AB - Colonoscopy is an important diagnostic and therapeutic tool that may also be useful in the surveillance of patients after curative resection of colorectal cancer. The yield of colonoscopy and the frequency with which it should be performed after operation, however, have not been clearly defined. Over the past 10 years, we have examined these patients annually with colonoscopy or barium enema. This study evaluates the results of a specifically designed protocol that followed 174 patients. Counting all sites, colorectal cancer recurred in 57 of 174 patients, three-quarters within the first 24 months. Nine anastomotic recurrences were detected in the 12-30 month interval; none was reoperated for cure; however, 4 metachronous colon cancers were found and resected for cure. In addition, 30 polyps larger than 1 cm in size and 7 villous adenomas were removed in 30 patients. Combined, these findings represent an interval yield of 3-5% per year. Based on these results and other reports, we recommend that patients undergo colonoscopy annually at least for the first 6 years postresection of colorectal cancer. The detection of new primary tumors and possibly predisposing lesions becomes more important in these patients than detection and cure of recurrent disease. PMID- 2327100 TI - Bleeding peptic ulcer: a prospective evaluation of risk factors for rebleeding and mortality. AB - Clinical, endoscopic, and laboratory data were collected prospectively in 701 patients with bleeding peptic ulcer. The overall rebleeding rate was 16.1% and increased the risk of a fatal outcome by 17 fold (1.2% versus 20.6%, p less than 0.001). Rebleeding was documented in more than 75% of the group who did not survive following initial conservative management. Rebleeding was more likely (24.1% versus 14.2%, p less than 0.02) when shock was present on admission and the risk of a rebleed was doubled in patients over 60 years of age (22.1% versus 10.9%, p less than 0.001). Ulcers greater than 1 cm in size carried twice the risk of rebleeding (23.9% versus 12.4%, p less than 0.002). Concomitant medical illness had a significant adverse effect on outcome (p less than 0.05). Shock on admission was associated with a doubling of mortality figures (9.5% versus 3.7%, p less than 0.01). The identification of endoscopic stigmata of recent hemorrhage (ESRH) tripled the risk of mortality (7.5% versus 2.4%, p less than 0.002), ESRH were more frequently encountered when ulcer size was larger than 1 cm (61.4% versus 39.8%, p less than 0.001). Respective mortality rates for ulcers less than or equal to 1 cm and greater than 1 cm in size were 1.6% and 12.5% (p less than 0.001), corresponding mortality figures for patients over 60 years of age being 4.4% and 16.4% (p less than 0.002). The risk of a rebleed tripled (6.7% versus 2.6%, p less than 0.02) when ESRH were evident. There was a 6-fold increase in mortality following emergency surgery when compared with conservative management of patients in whom no surgical intervention was necessary (2.6% versus 14.9%, p less than 0.001). In summary, age over 60 years, previous medical illness, shock on admission, large ulcer size, and ESRH were each associated with an increased risk of rebleeding and mortality. PMID- 2327101 TI - Perioperative antibiotic prophylaxis in cardiovascular surgery: a prospective randomized comparative trial of cefazolin versus ceftriaxone. PMID- 2327102 TI - The metabolism of chlorpromazine N-oxide in man and dog. AB - 1. The metabolism of chlorpromazine N-oxide was studied in female dogs and adult male humans after a single oral dose. 2. There was extensive metabolism in both species in that between four and seven metabolites were separately identified in urine and faeces. Apart from chlorpromazine N-oxide, chlorpromazine N,S-dioxide was the only isolated metabolite which retained the N-oxide group. The other identified metabolites were chlorpromazine and its 7-hydroxy, sulphoxide, N desmethyl, 7-hydroxy-N-desmethyl and N-desmethylsulphoxide derivatives. 3. With dog samples, metabolites were separated by h.p.l.c. and individually collected prior to mass spectrometric analysis. With human samples, metabolites were directly subjected to h.p.l.c.-mass spectrometric determination. With all metabolites their structures were confirmed by direct comparison of their mass spectra and chromatographic behaviours with those of authentic samples. 4. The metabolites identified in urine and faeces were for the most part the same in both species, with the exceptions that chlorpromazine N-oxide was identified in the faeces of dog only and 7-hydroxy-N-desmethylchlorpromazine was identified in the urine of man only. 5. The observation of N-oxide compounds in the excreta of both man and dog contrasted with that for the previously studied rat, where no such compounds were detected. PMID- 2327103 TI - Metabolism of low-dose paracetamol in patients with chronic neurological disease. AB - 1. Low dose (500 mg) paracetamol (acetaminophen) was administered to patients with Parkinson's disease, motor neurone disease and to age-matched controls. 2. At this low dose level the controls excreted proportionately more sulphate and less glucuronide conjugate than has been reported for administration of 1000 mg of paracetamol. 3. Both groups of patients with chronic neurological disease excreted decreased amounts of paracetamol sulphate (control mean 11.2 +/- 5.4% dose; Parkinson's disease 3.9 +/- 3.7%; motor neurone disease, 5.0 +/ 4.1%). 4. The mean ratio of excretion of paracetamol sulphate/paracetamol glucuronide was 5.6 +/- 11.7 in controls, but 1.1 +/- 1.7 and 1.2 +/- 1.7 in Parkinson's disease and motor neurone disease respectively. These differences are statistically significant (p less than 0.001). PMID- 2327104 TI - On the formation of carbamate glucuronides. PMID- 2327105 TI - Differential induction of 3-ethyl-2,6-dimethyl-4H-pyrido (1,2-alpha)pyrimidin-4 one metabolism by phenobarbital and 3-methylcholanthrene in microsomes and isolated perfused rat liver. AB - 1. The in vitro metabolism of 3-ethyl-2,6-dimethyl-4H-[2-14C]pyrido(1,2 alpha)pyrimidin-4-one (PYPY) was studied in liver microsomes and isolated perfused liver of 3-methylcholanthrene (MC) or phenobarbital (PB)-treated, and untreated rats. 2. Hydroxylation of the alkyl substituents was the main metabolic pathway for PYPY in both in vitro systems of untreated, and MC-treated animals, but with different proportions of the metabolites. PB enhanced the rate of ring hydroxylation, especially in the microsomes, and the product of this reaction became the main metabolite of PYPY biotransformation. Ring hydroxylation reactions in the microsomes and in the isolated perfused liver led to different products. 3. Differences arose in the rate of some oxidative reactions measured in the two in vitro systems resulting in altered metabolic patterns. PB enhanced not only quantitative but qualitative differences in the two systems. 4. The altered metabolite profile observed with whole liver compared with the products of microsomes, and the enhanced amount of water-soluble metabolites due to PB treatment in experiments with perfused liver indicate the involvement of further metabolic processes, perhaps conjugation reactions, in PYPY metabolism in the perfused liver. 5. The differences observed in the inducibility of some oxidative reactions by MC and PB indicate the involvement of at least three distinct cytochrome P-450 isozymes in the metabolism of PYPY. PMID- 2327106 TI - The disposition of an antileishmanial 8-aminoquinoline drug in the isolated perfused rat liver: thermospray liquid chromatography-mass spectrometry identification of metabolites. AB - 1. The disposition of the candidate antileishmanial drug 8 (diethylaminohexylamino-6-methoxy-4-methyl quinoline dihydrochloride (I) has been investigated in the isolated perfused rat liver preparation after the administration of 5 mg/kg (25 microCi) of 14C-I. 2. The perfusate concentration of unchanged I declined biexponentially over the 4 h study period, with a distribution t1/2 of 3.3 +/- 0.3 min and a terminal t1/2 of 35.4 +/- 13.6 min. The area under the perfusate plasma concentration/time curve (AUC0-last time point) was 53.3 +/- 15.7 micrograms min/ml, representing 96% of the area under the curve extrapolated to infinity. the perfusate contained predominantly the carboxylic acid metabolite of I, as well as trace quantities of metabolites detected and identified in bile. 3. Biliary excretion of total 14C accounted for 18.2 +/- 5.0% of the dose, only 2.8 +/- 0.7% was identified by h.p.l.c. analysis as unchanged I. The remainder of the bile contained the desethyl metabolite of I as well as a minimum of 12 more polar metabolites. After 4 h, a total of 39.0 +/- 8.3% of dosed 14C was recovered from the liver tissue. Subcellular fractionation of the livers revealed 24.6 +/- 2.2% of 14C to be located in the 10,000 g pellet. 4. Thermospray liquid chromatography-mass spectrometry analysis of untreated bile and bile treated with beta-glucuronidase or aryl sulphatase permitted identification of some of these metabolites, revealing the presence of the parent drug, desethyl metabolite, 6-desmethyl glucuronide, the 6-desmethyl desethyl glucuronide and the side-chain cleaved 8-amino N-glucuronide metabolites of I, as well as the 6-desmethyl sulphate and the 6-desmethyl desethyl sulphate. Two dihydroxylated metabolites were also detected; however, further structure elucidation is required for unambiguous identification. PMID- 2327107 TI - The metabolism of 2,4-dibromo-17 alpha-ethynyl[6,7-3H]oestradiol in the rat. AB - 1. The metabolism of 2,4-dibromoethynyloestradiol (2,4-DBEE2) in the rat was studied in order to determine the influence of ring-A substituents on the phase I biotransformations of oestrogens. 2. 2,4-Dibromo-17 alpha-ethynyl[6,7 3H]oestradiol was synthesized by the one-stage bromination of 17 alpha ethynyl[6,7-3H]oestradiol (EE2) with N-bromoacetamide, and administered (30 micrograms/kg, i.v.) to anaesthetized male and female rats. 3. A single metabolite, identified as a glucuronide of 2,4-DBEE2, was rapidly and extensively eliminated in bile by male rats (83% of the dose over 6 h). Females excreted additional minor conjugated metabolites. Neither unchanged 2,4-DBEE2 nor EE2 was detected in bile. 4. The hepatic residues after 6 h (percentage of dose) were 2.7% and 3.4% in male and female rats, respectively, whilst less than 0.1% per organ(s) was found in kidneys, heart, spleen, lungs and brain. 5. 2,4-Dibromo substitution of EE2 effectively blocked all phase I biotransformations whilst not limiting glucuronylation in male rats, but did not entirely preclude phase I metabolism in females. The inertness of 2,4-DBEE2 to ring-A hydroxylation in male rats conforms with the insignificant debromination of 2,4-dibromoestradiol by hepatic microsomes. PMID- 2327108 TI - Kinetics of in vitro metabolism of methoxyphenamine in rats. AB - 1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P 450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P 450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin. PMID- 2327109 TI - Chemical synthesis of dual-radiolabelled cyclandelate and its metabolism in rat hepatocytes and mouse J774 cells. AB - 1. The chemical synthesis of 3,3,5-trimethyl[1-3H]cyclohexanol, 3,3,5 trimethyl[2,3-3H]cyclohexanol and 3,3,5-trimethyl[2,3-3H]cyclohexanyl[1 14C]mandelate (cyclandelate) are described. The ratio of 3H/14C radioactivity in the ester was 27:1. 2. Cultured rat hepatocytes accumulated trimethylcyclohexanol rapidly and excreted its glucuronide into the culture medium. Rat hepatocytes also accumulated cyclandelate rapidly, hydrolysing the ester and excreting trimethylcyclohexanol into the medium. This trimethylcyclohexanol then re-entered the cells and was converted to its glucuronide prior to excretion. 3. In contrast, no hydrolysis of cyclandelate was seen on incubation with J774 cells, a transformed mouse macrophage. 4. Similar differences in hydrolytic activity were seen with microsomal fractions prepared from rat liver and J774 cells. Hepatic microsomes caused a rapid hydrolysis of cyclandelate while no hydrolysis was detectable after incubations of over an hour with J774 microsomes. 5. This difference in hydrolytic activity may have important implications for the action of cyclandelate on cholesterol metabolism in extrahepatic tissues. PMID- 2327110 TI - Characterization of products formed by the reaction of 14C sulphamethazinediazonium tetrafluoroborate with natural products. AB - 1. When bovine serum albumin (BSA) was incubated with 4-[N-(4,6-dimethyl-2 pyrimidinyl)sulphonamido] [U-14C]benzenediazonium tetrafluoroborate (14C-SDTFB) in vitro approx. half of the 14C-activity was bound (14C-BSA). Cysteine, N ethylmaleimide, p-chloromercuribenzoate and iodoacetamide inhibited the formation of 14C-BSA. 2. When SDTFB was reacted with cysteine four major products were formed. These were identified as 3-(4-[N-(4,6-dimethyl-2 pyrimidinyl)benzenesulphonamido] diazothio)-2-aminopropionic acid (cys-SDAS), 3 (4-[4,6-dimethyl-2-pyrimidinyl) benzenesulphonamido]thio)-2-aminopropionic acid (cys-Sulmet), 4-hydroxy-N-(4,6-dimethyl-2-pyrimidinyl)benzenesulphonamide (hydroxy-Sulmet) and N-(4,6-dimethyl-2-pyrimidinyl)benzenesulphonamide (desamino Sulmet). Diazosulphides were also formed when SDTFB was incubated with thiophenol and glutathione. 3. The diazosulphides reacted with N,N-dimethylaniline (DMA) and 2-naphthol to yield diazo compounds in 22-29% yield; when 14C-BSA was reacted with DMA under the same conditions, a diazo compound was formed-but only in 2% yield. 4. Cys-SDAS when incubated overnight (approx. 16 h) in aqueous solutions (pH 3, 5 and 8) decomposed to yield desamino-Sulmet (30-39%), hydroxy-Sulmet (13 21%), and other unidentified soluble products (24-36%); when 14C-BSA was incubated under the same conditions only 3-4% of the 14C became dissociated from BSA and only a trace amount of desamino-Sulmet was formed. 5. When 14C-SDTFB was incubated with calf thymus DNA at pH3, some of the 14C became associated with the DNA (14C-DNA). However, most of the 14C became dissociated from 14C-DNA when the latter was incubated overnight in aqueous solutions; a minor dissociation product was identified as 14C-desamino-Sulmet. PMID- 2327111 TI - Identification of a dithiol intermediate metabolite of malotilate in rats. AB - 1. A chemically unstable dithiol intermediate metabolite of malotilate was identified by g.l.c.-mass spectrometry after conversion of the dithiol to a stable derivative by a cyclization reaction with 1,3-dichloroacetone. The dithiol, namely, 2,2-di(isopropoxycarbonyl)ethylene-1,1-dithiol, was present in rat liver at low concentrations. 2. A study of glucuronidation in vitro indicated that the dithiol was converted to the corresponding thio-glucuronide by rat hepatic microsomal enzymes. 3. It was thus confirmed that metabolism of malotilate proceeds via the dithiol intermediate to form the thio-glucuronide, which is a major metabolic pathway. PMID- 2327112 TI - The metabolism of (+-)-methylephedrine in rat and man. AB - 1. Urinary metabolites of methylephedrine and their excretion after oral administration to rat and human volunteers have been studied. 2. The unchanged drug, ephedrine, norephedrine, their aromatic hydroxylated compounds and methylephedrine N-oxide were found in rat urine. The same metabolites, except the p-hydroxylated metabolites, were detected in human urine. The most abundant metabolite in rat urine was methylephedrine N-oxide, and in human urine was the unchanged drug. 3. Metabolites excreted in three days after administration of the drug to rat amounted to about 54% of the dose and those after administration to man, 70-72%. PMID- 2327113 TI - Reducing the duration of prophylactic antibiotic use through computer monitoring of surgical patients. AB - The use of antibiotic prophylaxis for unnecessarily prolonged periods after surgical procedures can contribute to increased health care costs and adverse drug reactions as well as the development of antibiotic-resistant infections. Hospitals are under economic pressures to develop methods to control the excessive use of these drugs. We expanded the capabilities of our hospital information system to monitor the duration of surgical antibiotic prophylaxis. For six months during one year we used the computer system to monitor antibiotics received by every surgical patient and to identify patients receiving antibiotic prophylaxis longer than was deemed necessary according to generally accepted guidelines. For six months in the following year we used the system to monitor and identify the same types of patients and clinical pharmacists placed antibiotic "stop orders" in the charts of the patients identified by the computer. Surgical patients received an average of 19 doses of antibiotics in the first year compared with 13 doses in the second year (p less than 0.001). The average cost of antibiotics received more than 48 hours after the operation was $42 less per patient in year 2 than in year 1, resulting in a potential cost savings of $44,562 in six months. The computer system was found to be an efficient tool for monitoring all antibiotics given to surgical patients and identifying patients receiving antibiotic prophylaxis longer than necessary. Clinical use of this system appears to have resulted in improved usage of antibiotic prophylaxis. PMID- 2327114 TI - Clinical utility of a saliva alcohol dipstick estimate of serum ethanol concentrations in the emergency department. AB - Rapid determination of serum ethanol concentrations can be a useful adjunct in evaluating patients with decreased levels of consciousness. Previous reports suggest that saliva ethanol concentrations measured by a colorimetric saliva dipstick assay correlate well with serum ethanol concentrations and could be useful in the emergency department. We compared saliva dipstick assay results with concurrent serum ethanol measurements in 67 emergency department patients with altered mental status. Color changes of the stick are calibrated to reflect serum ethanol concentrations of negative (no color change), 4.3 mmol/L, 10.8 mmol/L, 21.7 mmol/L, and greater than or equal to 65.1 mmol/L. Emergency department staff were instructed to conduct the measurement according to the manufacturer's directions and round up equivocal results to the next highest concentration. Serum ethanol concentrations (mean +/- SD) grouped by dipstick results were: negative, 5.2 +/- 13.1 mmol/L; 4.3 mmol/L, 29.1 +/- 18.0 mmol/L; 10.8 mmol/L, 46.6 +/- 27.6 mmol/L; 21.7 mmol/L, 47.0 +/- 18.5 mmol/L; and 65.1 mmol/L, 62.4 +/- 24.2 mmol/L. There were 12 false-negative and 2 false-positive results. Correlation between dipstick results and serum ethanol concentrations was rho = 0.611 (p less than 0.0005). The lack of accuracy of the saliva dipstick measurements and the high number of false-negative results make it a poor choice for determining alcohol use in the emergency department patient. PMID- 2327115 TI - Suspected ciprofloxacin-induced interstitial nephritis. AB - Interstitial nephritis is a rare but serious adverse effect of many drugs and usually is diagnosed by clinical signs and symptoms of hematuria, proteinuria, eosinophilia, fever, azotemia, and rash. Ciprofloxacin is one drug that has been reported to cause interstitial nephritis. Renal toxicities have been reported in less than one percent of the patients receiving ciprofloxacin therapy. Limited documentation of this adverse effect exists in the literature. This article describes a patient with suspected ciprofloxacin-induced interstitial nephritis. PMID- 2327116 TI - Transition from Lanoxin capsules to Lanoxin tablets in the debilitated elderly. AB - Lanoxin capsules are more rapidly absorbed than tablets, with less contact by intestinal bacteria capable of metabolizing digoxin to an inactive form. The manufacturer states that the doses of a 0.25-mg tablet and a 0.20-mg capsule are approximately equivalent. Thirty-nine patients had digoxin concentrations determined within three months of the transition from Lanoxin capsules to Lanoxin tablets, and again one month after starting the tablets. Patients were excluded if confounding medications had been changed before the two blood draws or if they had an acute disease exacerbation. The mean digoxin concentration on capsules was 0.92 +/- 26 ng/mL. The mean concentration on comparable doses of tablets was 1.03 +/- 29 ng/mL, with a mean difference of 0.11 ng/mL. Paired comparisons were significantly higher on the tablets (t = 3.203, p = 0.0028). PMID- 2327117 TI - A model of methods for influencing prescribing: Part I. A review of prescribing models, persuasion theories, and administrative and educational methods. AB - The purpose of this literature review is to develop a model of methods to be used to influence prescribing. Four bodies of literature were identified as being important for developing the model: (1) Theoretical prescribing models furnish information concerning factors that affect prescribing and how prescribing decisions are made. (2) Theories of persuasion provide insight into important components of educational communications. (3) Research articles of programs to improve prescribing identify types of programs that have been found to be successful. (4) Theories of human inference describe how judgments are formulated and identify errors in judgment that can play a role in prescribing. This review is presented in two parts. This article reviews prescribing models, theories of persuasion, studies of administrative programs to control prescribing, and sub optimally designed studies of educational efforts to influence drug prescribing. PMID- 2327118 TI - Aztreonam adverse reactions. PMID- 2327119 TI - Ciprofloxacin Staphylococcus aureus resistance. PMID- 2327120 TI - Drop size and systemic adverse effects in timolol ophthalmic solution. PMID- 2327121 TI - Netilmicin sulfate stability in combination with metronidazole or ranitidine hydrochloride in NaCl 0.9% infusion. PMID- 2327122 TI - [Aspects of hospital hygiene in Legionella infections]. AB - Legionella inevitably are imported from natural reservoirs into drinking-water supplies. Bacterial growth predominantly occurs at water temperatures between 40 degrees C und 50 degrees C (104 degrees F and 122 degrees F). Heat conduction to insufficiently insulated cold water tubes implies the possibility of increased contamination also there. Problems with contamination arise in parts of the water supplies with stagnant warm water. Therefore, reservoirs should be descaled regularly. In general, for prophylaxis are recommended raising the temperature of warm water to 60 degrees C (140 degrees F), regular microbiological control of water quality and regular technical maintenance of waterworks where warm water stagnates for some time. Patients bearing a higher risk of Legionella-infections require intensified precautionary measures. The diagnosis of legionellosis should be based on the direct evidence of immunofluorescence-stained microorganisms. Finding increased antibody titers alone is not always correlated with the response to Legionella-specific therapy. PMID- 2327123 TI - [Refuse disposal at the hospital]. AB - For the classification of hospital-wastes in the categories infectious contaminate or special waste are only significant views of the prevention by nosocomial infection in the hospital. Solely infectious waste become removed hospital-intern and -extern on conditions of hygienic prevention, namely through secure packing during the transport, combustion or desinfection. Special wastes to be defeated by special-conditions. The hygienist of the hospital is only competent for the classification of the wastes in the hospital as well as for their refuse. PMID- 2327124 TI - [The significance of disinfection in control of veterinary communicable diseases]. AB - On a series of epi- resp. enzootic turn of infectious diseases in animal stocks has been shown that disinfection can not be accomplished stereotyped. Dependent on germ, epizootologic peculiarity and resistance of the host the worth of disinfection within the bounds of prophylaxis has been indicated for a number of infectious diseases. PMID- 2327125 TI - [Evaluation of lead poisoning in an exposed pediatric population before and following control of the source]. AB - In the surroundings of a large lead mill, which emitted in the 70 years up to 250 t of lead per year and where the maximum allowable daily immission concentrations of 0.7 microgram/m3 were exceeded by a factor of 20-30, in children mean blood levels above 45 micrograms/100 ml blood were determined. At the beginning of the 80 years the mill had modernised the filter constructions. The emission was decreased to 10% of the original value. The immissions decreased by 50% and the blood lead level in children by 10 to 20%. It could be shown, that the soil was furthermore contaminated and vegetables and fruits contained increased lead levels. Additional measures are to be realised to diminish exposure. The situation described is an example for the long latency of positive changes in the environment and in the health state of the population following environmental preventive measures. PMID- 2327126 TI - [Health protection of boiler cleaners]. AB - The working conditions of the boiler cleaner are demonstrated after the working hygienic complex analysis. By reason of the manifold exposition facing one another 5 working hygienic environmental factors with the index 0.0 and 0.2 as well as by carrying of the breathing--and fall protection media, the working load capacity is to value as especially high. It is reported about the results of the working hygienic fitness and control examinations. The conclusions for the situation modification are discussed. PMID- 2327127 TI - [Cataract in welders. Contribution of occupational exposure, references for recognition as an occupational disease and presentation of preventive measures]. AB - An analysis was made of all the cases of eye disease in welders caused by infrared radiation which have been recognized as occupational disease Bk 52 in the GDR by now. A comparative study was conducted and proposals for the definition of criteria for recognition as occupational disease were derived. The determination of exposure by means of suitable radiation measurement devices is described. Both the problems of measurement value acquisition and the evaluation of radiation loads are dealt with. The infrared radiation load of the eyes is quantified for several frequently used welding techniques. Various measuring values obtained in other industries and in the transport sector are given for comparison. Protective measures and the use of suitable face protections are discussed. Conclusions are drawn with regard to the health protection of welders against infrared radiation exposure. PMID- 2327128 TI - [Public health aspects of the hands]. AB - After explanation of the importance of hands for the transmission of infections the strategy for prevention of germ transmission was developed. In central position is thereby separation and measures of reduction of germ number according to their indication how hygienic handwashing, antiseptic handwashing, hygienic hand disinfection under the special consideration of virus disinfection and surgical hand disinfection. PMID- 2327129 TI - [The antimicrobial effectiveness of hand antiseptics]. AB - The new developed antimicrobial agent metacid (chlorine hydrate of polyhexamethylene guanidine) has been suggested to antiseptic of hands in 0.25% water/alcohole solution resp. 0.5% water solution by reason of its good antiseptic effectivity. Admixtures in soaps the agent is able to increase their antiseptic activity distinctly. Metacid in its effectivity can be compared to chlorhexidin. PMID- 2327130 TI - [Antisepsis of mucous membranes--current status and aspects of future development]. AB - The mucous membranes colonized by high numbers of microorganisms play a major role as a source of nosocomial infections. According to clinical requirements it seems reasonable to distinguish three modes of application of antiseptics: 1. single prophylactic (prior to mucosa-penetrating interventions), 2. repeated periodical (wound care, treatment of oral cavity in intubated patients, decontamination of granulocytopenic patients), 3. therapeutic (local mucosal infections) including treatment of carriers to prevent transmission and spread of pathogens. Active agents commonly in use are PVP-iodine, cation-active detergents (e.g. chlorhexidine), oxygen-releasing compounds and organic mercury compounds. Presently chlorhexidine and PVP-iodine are the most frequently applied of these antiseptics while the organic mercury compounds are less important because of limited efficacy, toxicological and ecological problems. Preliminary data from investigations using a newly developed antiseptic, octenidine, a bispyridine compound, demonstrate reduction factors comparable to those obtained by PVP iodine. Yet no standardized test methods for the efficacy of different substances and methods of application have been established. PMID- 2327131 TI - [The significance of disinfection in preventing nosocomial infections]. AB - Comparable analyses of the frequency of isolation at aerobic bacteria from clinical test material resp. from cockroaches (body surface and faecal contents) henced the epidemiological relationships which underline the necessity of complex and effective measures of disinfection on the prophylaxis of nosocomial infections. PMID- 2327132 TI - [Hygiene regimen in neonatology]. AB - Prophylaxis of contamination, disinfection, sterilization of needed materials and sterile handling are essential suppositions for a successful struggle against hospital infections during the neonatal period. Proposals are presented to the hygienic management at delivery stations, delivery-rooms and neonatal intensive care units. PMID- 2327133 TI - [Scintigraphic quantification of pulmonary pressure increase in mitral valve stenoses based thallium uptake by the lung]. AB - 30 patients (24 fm, 6 m) with angiographically proven mitral stenosis as well as 10 healthy controls were investigated by wedge catheterism and thallium-201 scintigraphy to calculate the heart-lung quotient of the isotope. All patients with mitral stenosis could be discriminated from controls by a pathological increase of isotope concentration in the lungs. 4 groups could be subdivided: the first consisted of 8 patients with normal pulmonary artery pressure of x = 13.06 mm Hg and a normal heart-lung quotient less than 1.1. The second group of 15 patients showed passive pulmonary hypertension with a PAm of x = 27.57 mm Hg and heart-lung quotients between 1.1 and 1.4. A third group of 9 patients showed PAm of 36.76 mm Hg with reactive hypertension and a HLQ between 1.4 and 1.6. The last group of patients showed pulmonary hypertension of x = 45 mmHgPAm and a heart lung quotient of greater than 1.6. Scintigraphy alone allowed classification of the patients, so the value of this method is proven for pre- and postoperative strategy. PMID- 2327134 TI - [Retinol-binding protein, haptoglobin and ceruloplasmin--tumor markers in colorectal cancer?]. AB - Retinol-binding protein, haptoglobin and ceruloplasmin were determined in the plasma of patients with colorectal carcinoma. The comparison with a control group shows that retinol-binding is significantly decreased in colorectal carcinoma and that haptoglobin and ceruloplasmin are significantly elevated. The ROC-curves of the three parameters, however, display a sensitivity distinctly lower than that of CEA, so that any use in the clinical treatment of colorectal carcinoma cannot be expected from the determination of these substances. PMID- 2327135 TI - [Incidence of goiter and thyroiditis in chronic inflammatory rheumatism]. AB - In our investigations 201 patients with rheumatoid arthritis show in 127 cases according 63.2% (123 women = 71.1%; 4 women = 14.3%) and 32 patients with collagen diseases in 11 cases according 34.4% (11 women = 43.3%) a goiter. In comparison to a control group with a goiter incidence of 29.5% in women (168 out of 570 women), we found in female patients with rheumatoid arthritis or collagen diseases a clearly higher prevalence of goiter. But there was no difference of goiter frequency between the small groups of men. A second aim of our study was to investigate, whether an increased occurrence of the hypertrophic kind of Hashimoto's thyroiditis is to find in patients with rheumatic diseases, because of a possible association of two immunological induced affections. The results of sonographical, immunological and cytological examinations of the thyroid gland suggested no high responsibility of Hashimoto's thyroiditis for the goiter frequency in rheumatism. Only in three out of 201 investigated patients with rheumatoid arthritis (1.5%) we were able to diagnose this disease. In comparison to a rheumatologically healthy population out of the same catchment area (HT frequency less than 0.5%), indeed the morbidity rate in rheumatic patients seems to be 3 times higher. But for a goiter frequency of altogether 63.2% in this disease the Hashimoto's thyroiditis is only of very small importance. Other causes such as pharmacotherapy with goitrogenic antirheumatic drugs, conditions of iodine deficiency, disposition and probably also an increase of thyroid growth stimulating immunoglobulins may be alone or in combination or a much higher degree responsible for goiter development in patients with rheumatoid arthritis or collagen diseases. PMID- 2327136 TI - [Primary lymphoblastic lymphoma of the thyroid]. AB - Report is given on a 78-years-old woman with a primary lymphoblastic lymphoma of the thyroid gland. The lymphoma had invaded the trachea. An extrathyroid manifestation of the lymphoma was not found. There was no Hashimoto's thyroiditis. The patient died of bronchopneumonia and pulmonary embolism. PMID- 2327137 TI - [Kyrle disease in juvenile diabetes mellitus and chronic renal failure]. AB - We report on a 32-year-old female patient with chronic diabetes mellitus, type I, and chronic renal failure, who developed the typical clinical picture of hyperkeratosis follicularis et parafollicularis in cuteum penetrans (Kyrle's disease) within one year. Histological examination revealed a defective epidermal differentiation with hyper- and parakeratosis as well as premature keratinization as early as in the epidermal basal cell layer. Studies on lectin binding showed that the glycosylation process was impaired in both the epidermis and the basement membrane zone of the lesional skin. In addition, electron microscopic investigation revealed diabetic microangiopathy of the dermal vessels as well as marked ultrastructural alterations of the dermo-epidermal basal lamina. These findings confirm the association of diabetes mellitus with Kyrle's disease previously described; they make us suggest that Kyrle's disease might be characterized by a defective differentiation of the epidermis and the dermo epidermal junction--due to some alteration of the underlying glycosylation processes--rather than by a local disorder of keratinization. Regarding the clinical manifestation of the disease, both diabetes mellitus and chronic renal failure may play a part as precipitating factors. PMID- 2327138 TI - [Proliferative myositis]. AB - We report on a 42-year-old woman showing a rapidly growing tumor on her left flank; it was removed by surgery. Histological examination revealed the typical picture of proliferative myositis. Since the clinical symptoms of this disease are nonspecific, the diagnosis always depends on histological evidence. Despite its rapid growth and its cellular pleomorphism, proliferative myositis is a reactive process and has to be differentiated histologically from sarcoma of the soft tissue. PMID- 2327139 TI - [Dermatology 2000]. PMID- 2327140 TI - [Degenerative changes in schwannoma (neurilemmoma)]. AB - We report on a 51-year-old male patient showing a slowly growing, pedunculated, hairless tumor on the back of his head. The tumor grew up to the size of 4.2 cm in diameter, before it was removed by surgery. Histological examination revealed the typical picture of an ancient schwannoma (degenerated neurilemmoma). In spite of its highly atypical nuclei, the biological behavior of ancient schwannoma is benign, and it must be differentiated from malignant tumors of the nerve sheath. PMID- 2327141 TI - [Comment on the article by Prof. H. Tronnier, "Requests of the dermatologist from cosmetics" (Z Hautkr 1988; 63: 983-5)]. PMID- 2327142 TI - [Housing and the residential environment of the aged]. PMID- 2327143 TI - [Housing status and social networks for the elderly]. AB - There is a provable correlation between the housing conditions of elderly persons and their being attached to a network of aid they can rely on in cases of emergency and strain. The elderly living in one or two-family houses, for example, have several options of being supported. The elderly living in big city tenements on the other hand often lack such an abundance of relations. Integration into the circle of family members and relatives plays the major role for these quantitative framework conditions as well as for the immediate availability of assistance. Having a house of one's own increases the possibility of developing a well-functioning cross-generation support system within the family. If promotion of house construction was further adapted to this operating mechanism, support effects for social policy could be reached. At the same time it is imperative to encourage the development of informal support systems within the framework of socio-political initiatives. With the number of childless elderly persons increasing, such systems would partially compensate for the lack of family assistance through neighbourhood and other forms of self-support. PMID- 2327144 TI - [Sports for the elderly in a sports active aging society]. AB - The number of elderly people is growing. The next generation will grow older taking a more active part in sport than the present one. The halving of the number of younger members of the population, and thus the declining number of people participating in sport is furthering the interest of sports clubs in the elderly. At present the programmes of sport for the elderly run by sports associations are still at an initial stage. Sports clubs and the planning of the development of sports facilities in towns and villages are confronted by a new situation-that of the growing number of elderly people taking an active part in sport. In 1988/89 the Institute for Development Planning and Structural Research at the University of Hanover carried out five regional case studies into the sports behaviour of the elderly and into their motives and expectations with regard to sport. More than 10,000 people participated in the representative surveys. They came from towns and villages with a rural character in the Federal Republic of Germany. Structures and development perspectives on the subject of "Sport by Elderly" are outlined from a social science aspect. PMID- 2327145 TI - [New housing and life styles for the aged. Aging in a residential community]. AB - The decision to share a flat and live in community for old people marks the step into a new, unfamiliar life situation. Long-fostered outlooks and attitudes have to be reconsidered and perhaps modified. Living in community requires such vital qualities as self-reflexion and empathy. The new life-style may be cumbersome, often confusing; on the other hand, it strips aging of its character of waning life-time. It renders the later years a proper phase of life offering its own chances. PMID- 2327146 TI - Social and environmental factors and atypical depression in old age. AB - This community-based epidemiological survey is concerned with relationships between social and environmental factors and atypical depression in a Finnish population aged 60 years or over. The occurrence of atypical depression was related to older age, widowed or divorced marital status, having moved during the previous few years, living in a small dwelling near the local population center, having neighbors living in the same building, living alone, being frequently alone, a low number of hobbies and many long-standing or current social stress factors. In addition, the atypical depressive persons felt that elderly people were not appreciated. The log-linear model constructed for atypical depressive persons revealed five subgroups. The first was characterized by living alone and being widowed or divorced, the second by living alone and having a low number of hobbies and a high incidence of long-standing social stress factors, the third by being frequently alone and being widowed or divorced, the fourth by a low number of hobbies and a low incidence of actual social stress factors, and the fifth by living alone and having a high incidence of long-standing social stress factors and a low incidence of actual social stress factors. PMID- 2327147 TI - [Subfractions of high density lipoproteins in relation to age]. AB - In dependence on age women show both elevated levels of serum triglycerides and changes of lipid composition of HDL. A decrease of HDL- and HDL2-cholesterol levels and an increase of HDL- and HDL2-triglyceride concentrations are seen in the group of older persons. The concentration of HDL3-phospholipids decreases in dependence on aging. The content of triglycerides and the relation triglyceride/cholesterol of the subfraction HDL2, but not of HDL3, show positive correlations with the level of serum triglycerides. These changes are related to an age-dependent decrease of post-heparin lipolytic activity and a remodulation of HDL in dependence on the relation of the concentration of triglyceride rich lipoproteins and HDL. PMID- 2327148 TI - [Constitutional peculiarities of the bioelectric activity of the brain]. AB - Based on the data obtained in exploring the processes of background bioelectric activity of the brain by means of Karhunen-Loeve decomposition, the authors have revealed constitutional peculiarities of EEG characterizing the systemic mechanisms of hereditary disposition either to longevity or to cerebral vascular pathology. PMID- 2327149 TI - Epidemiology and eradication strategy for hepatitis B in Europe. The European Regional Study Group. AB - In Europe, only approximately 1% of the general population are chronic carriers of the hepatitis B surface antigen (HBsAg) but hepatitis B is unevenly distributed in the region. Based on the prevalence of HBsAg, the region may be divided into three hepatitis B epidemiological patterns: the UK and the Scandinavian countries (less than 0.1%); most countries in Western Europe (0.1 0.5%); and countries situated along the Mediterranean Sea and in Eastern Europe (1-5%). Existing screening and vaccination programmes depend on such factors as the carrier rate of the indigenous population and the influx of immigrants from highly endemic areas. Vaccination of health care workers is, in general, advised but not required. The accent has been placed, in most countries, on the screening of pregnant women for the presence of HBsAg and the vaccination of newborns of carrier mothers. Education programmes are needed to enhance awareness of general practitioners regarding these risk groups. The institution of mass vaccination will depend upon the cost of vaccine, although the cost factor is less important in Europe than in developing countries. PMID- 2327150 TI - Strategy for the control of hepatitis B virus infection in the Middle East and North Africa. The Middle East Regional Study Group. AB - Hepatitis B virus (HBV) infection and HBV-associated diseases are prevalent in many parts of the Middle East and North Africa. Postnatal horizontal childhood transmission appears to be the predominant method by which high hepatitis B carrier rates are maintained. To control hepatitis B in this region, mass immunization should be initiated prior to one year of age. This effort would be most cost-beneficial when integrated into the Expanded Programme of Immunization (EPI) and should be preceded by demonstration projects designed to gather practical data on the impact, methods and feasibility of such programmes which can subsequently be used to expand the immunization programme to other parts of the region. PMID- 2327151 TI - Hepatitis B surface antigen reactivity in man due to a new variant of hepatitis B virus. AB - A new type of hepatitis B virus (HBV) infection has been encountered in Senegalese infants and French adults characterized by serum hepatitis B surface antigen (HBsAg) without antibodies to the core antigen (anti-HBc). As the infection is not associated with the presence of the e antigen, it differs from HBV in its core antigen. After the loss of HBsAg, neither anti-HBc nor antibodies to HBsAg (anti-HBs) become detectable. This new infection (called HBV2 as opposed to the classical HBV1 infection) was found in infants with anti-HBs, either naturally acquired or produced by immunization against HBV. The use of monoclonal anti-HBs antibodies showed that two epitopes of HBV1 surface antigen could be detected in HBV2-positive sera. HBV DNA sequences could only be found in one of 15 HBV2-infected children using a DNA-DNA hybridization procedure; low levels of HBV DNA were also detected in 58% of the HBsAg-positive adult sera tested. If this new infection, apparently related to HBV1, is shown to cause chronic liver disease, hepatitis B vaccine should also contain surface antigen from HBV2. PMID- 2327152 TI - Coronary artery bypass surgery: emerging trends in mortality. AB - In a consecutive series of 4,697 patients undergoing coronary artery bypass surgery, these risk factors were found to be significant for increased postoperative mortality: age greater than 70, female sex, unstable angina, prior myocardial infarction, hypertension, diabetes mellitus, and ejection fraction less than .40. A comparison by year (1980-1988) revealed a steadily increasing incidence of these risk factors. Future analysis of coronary artery bypass mortality should include risk-factor stratification. PMID- 2327153 TI - Precertification: don't let it hurt your bottom line. PMID- 2327154 TI - Virginia Medical's guide to precertification in Virginia. PMID- 2327155 TI - Tinea nigra palmaris in Virginia: case report. PMID- 2327156 TI - Changing perspectives: coronary artery disease. PMID- 2327157 TI - [Quality assurance needs nurse's expertise. Interview by Kaj Nyman]. PMID- 2327158 TI - [Proposal to association committee: improve cooperation with students]. PMID- 2327159 TI - [Lars has AIDS--a more dignified life with care at home. Interview by Monika Trozell]. PMID- 2327160 TI - [When Allis talked about work organization Carlsson listened]. PMID- 2327161 TI - [Infants in Nicaragua are malnourished already at birth]. PMID- 2327162 TI - [We hope that many will become nurses. Interview by Ewa Stackelberg]. PMID- 2327163 TI - [The prenatal diagnosis of Herlitz's borderline epidermolysis bullosa letalis]. AB - Methods of morphologic prenatal diagnosis permit optimizing the medicogenetic prognosis thus preventing the birth of patients with severe incurable forms of congenital bullous epidermolysis and preserve normal pregnancy in risk-group females. Studies on the estimation of the prognostic and prophylactic value of methods for the prenatal diagnosis of congenital dermatoses are necessary. PMID- 2327164 TI - [Disordered differentiation of the immunocompetent cells in sarcoidosis and sarcoids of the skin]. AB - The findings of immunologic examinations of patients with sarcoidosis and sarcoids of the skin are reviewed. Immune disorders in these conditions are identical. Lowered cellular immunity activity and elevated humoral immunity activity have been revealed. Increased level of circulating immune complexes evidences the process activity in both sarcoidosis and sarcoids of the skin. The intensity of immune disorders does not depend on the disease duration, form, and dissemination. PMID- 2327165 TI - [The immune status of patients with lymphoproliferative diseases of the skin and Kaposi's sarcoma]. AB - Manifest disorders of cellular and humoral immunity are detectable with the use of immunologic tests in patients with mycosis fungoides, skin reticulosis, and Kaposi's sarcoma. The pattern of changes in Kaposi's sarcoma differs from that in malignant lymphomas of the skin. The detected immune status disorders necessitate the use of immunomodulators in combined therapy of such patients. PMID- 2327166 TI - [The interphase chromatin of lymphocyte nuclei in psoriasis patients]. AB - Lymphocytic nuclei interphase chromatin was examined with the use of automated morphometry in psoriasis patients treated by different methods. Fifty optic and geometric parameters of lymphocytes were under study; the nuclear size and relative contrast, relative contrast of nongranular component, and chromatin pattern determined visually were found the most informative characteristics. The results evidence significant differences between the reference group of normal subjects and psoriasis patients. After treatment a tendency to normalization of the shifted parameters of interphase chromatin can be traced; PUVA therapy intensifies this process, and the parameters reach the reference values. PMID- 2327167 TI - [A method for control over the training of student physicians in a department of skin and venereal diseases]. AB - The authors emphasize the significance of independent work of physicians, trained at the Chair, for the improvement of their continuous education. The role of the teacher in this process is discussed, the methods of training are presented, and various forms of independent work of the physicians in hospitals and outside the classrooms are described. PMID- 2327168 TI - [The selection of the territories for conducting epidemiological research on the prevalence of skin and venereal diseases]. AB - The results of studies aimed at the formation of representative territories at republics, regions, and cities for the epidemiologic surveys are analyzed. The representative areas that were singled out in these studies are recommended to be used for research in dermatology and venereology, aimed at the population health fortification. PMID- 2327169 TI - [New approaches to characterizing the immune status of patients with lupus erythematosus using immunoenzyme testing]. AB - A total of 78 patients with various forms of lupus erythematosus (LE) were examined with the use of enzyme immunoassay (EIA) to test the possibility of antibody production in response to neuraminidase, an antigenic stimulant. Positive EIA results were recorded in 54.5% of patients with the integument LE forms and in 58.3% of those with systemic LE. The intensity of antibody production depended on the patients' sex (it was more active in females), age, and the disease duration. In the course of therapy negative results replace positive ones mostly in the patients with a disease of not long standing. A correlation was revealed between the content of circulating immune complexes measured by polyethylene glycol sedimentation and the levels of IgM and IgG. The detected relationship between the level of antineuraminidase antibodies and features of the disease course and therapy, agreement of this parameter with other immunologic characteristics, availability and informative value of the method recommend it for the assessment of immunity disorders in LE patients. PMID- 2327170 TI - [The immunocorrective therapy of pyoderma caused by staphylococci multiply resistant to antibiotics]. AB - Examinations of 126 patients with staphylococcal pyodermas have helped detect a relationship between the total antibiotic sensitivity of staphylococci isolated from the involved skin and the patient's immunity status. The total antibiotic sensitivity of staphylococci in directly proportional to the blood level of T lymphocytes, to the degree of their sensitization to staphylococcus in the leukocyte migration inhibition test, and to the value of IgM/IgG ratio. A new synthetic preparation of thymus, thymogen, had a modulating effect on the lymphocytes of pyoderma patients, manifesting by the increment of the total count of T-lymphocytes and T-helpers. A reduction of the total antibiotic resistance of the agent in foci of skin infection and normalization of the immunologic reactivity parameters were recorded in 23 patients with chronic pyodermas after a course of thymogen therapy. An effective method for the management of chronic pyoderma by a combination of thymogen with antibiotics is suggested. PMID- 2327171 TI - [Delayed hypersensitivity to staphylococcal antigens in patients with staphylodermas]. AB - Basing on analysis of delayed skin reactions to staphylococcal vaccine, on findings of pathohistologic examinations of the skin in foci of delayed type hypersensitivity, on the parameters of the lymphocyte, monocyte, and neutrophil migration into these foci, as well as on the clinical parameters and findings of the spontaneous rosette-formation, lymphocyte blastogenesis, leukocyte migration inhibition tests with the specific antigen, and DNCB skin test, carried out in 312 patients with staphylodermas, the author comes to a conclusion on the protective role of delayed type hypersensitivity to Staphylococcus, reveals some mechanisms of the formation of skin response reactions, and points to some factors responsible for inhibition of these reactions. PMID- 2327172 TI - [Hyperimmune antistaphylococcal plasma in the treatment of psoriasis patients]. AB - The immune status parameters were examined in 132 patients with various dissemination, activity, and length of the process, in whom treatment with hyperimmune antistaphylococcal plasma brought different clinical effect. PMID- 2327173 TI - [The use of leukocyte interferon in the combined therapy of condylomata acuminata of the genitals]. AB - A new method for the treatment of condyloma acuminatum is described: leukocytic interferon combined with liquid nitrogen cryotherapy. This treatment has resulted in a stable therapeutic effect. PMID- 2327174 TI - [Rowell's syndrome]. AB - Two cases with this rare syndrome are described, with a combination of lupus erythematosus and erythema multiforme exudativum. PMID- 2327175 TI - [The connection of Hebra's herpetiform impetigo to pustular psoriasis]. AB - Two clinical cases of Hebra's impetigo herpetiformis are described. This rare dermatosis is regarded as a variant of pustular psoriasis and is difficult for differential diagnosis. PMID- 2327176 TI - [Bilateral circumscribed scleroderma of the face in children]. AB - Two cases of local scleroderma in children are described with bilateral symmetrical localization of the foci on the face, including a most rare site- round the eyes. A long follow-up of children with such a localization of the disease is necessary, because they may develop Romberg's hemiatrophy. PMID- 2327177 TI - [The combination of syphilis and HIV infection]. AB - Seven cases of a combined course of syphilis ad HIV infection are described. All the patients are men, homo- and bisexuals. No apparent clinical features of syphilis in these patients were detectable. Recommendations on the strategy of syphilis treatment in patients with HIV infection are given. PMID- 2327178 TI - [The combined treatment with doxycycline and methyluracil of a patient with lymphogranuloma venereum]. PMID- 2327179 TI - Cloning and sequencing of the ornithine carbamoyltransferase gene from Pachysolen tannophilus. AB - A fragment of DNA from a yeast Pachysolen tannophilus, bearing the ornithine carbamoyltransferase gene (OCTase, EC 2.1.3.3) has been cloned from a genomic library by functional complementation of the Escherichia coli OCT-negative mutant. The gene was located within the cloned segment of DNA and its coding sequence identified by DNA sequencing. This has indicated that P. tannophilus OCT gene encodes a 347 amino acid polypeptide, which shows 60% identity to the homologous Saccharomyces cerevisiae protein. The amino acid composition of its N terminus indicates that this protein is translocated across the mitochondrial membrane. The gene can be expressed in E. coli as well as in S. cerevisiae. Comparison with other OCTases confirms a high degree of conservation among these proteins. PMID- 2327180 TI - Interleukin-2 activated cells from peripheral blood of patients with systemic lupus erythematosus. AB - The effect of recombinant interleukin-2 (IL-2) on proliferative and cytotoxic response of peripheral blood mononuclear cells (PBMC) was investigated in a group of 21 patients with systemic lupus erythematosus (SLE). There was a significant decrease in thymidine uptake of peripheral blood mononuclear cells when compared with controls. However, IL-2 induced cytotoxicity was not diminished and minimal frequencies of lymphokine-activated killer (LAK) cells precursors remained in the range of control group. These data provide an evidence about the dissection between proliferative and cytotoxic response of PBMCs to exogenous interleukin-2 in patients with SLE in vitro. The factors contributing to this effect and the clinical significance of these findings remains to be answered. PMID- 2327181 TI - [Soluble interleukin 2 receptor (sIL-2R) in chronic polyarthritis]. AB - An ELISA was used to measure soluble interleukin-2 receptor (sIL-2R) in the sera and synovial fluid (SF) of patients with rheumatoid arthritis (RA). Patients with seropositive, as well as seronegative RA had raised levels of sIL-2R in serum and SF compared to patients with osteoarthritis and sex-age matched healthy subjects. According to literature, sIL-2R levels in the sera of RA-patients may be a useful marker of disease activity. Increased sIL-2R levels in SF show new aspects in pathophysiology of RA. PMID- 2327182 TI - [Duct-oriented classification of exocrine pancreatic carcinoma]. AB - Histogenetic classification was applied to 416 cases of human exocrine pancreas carcinoma. Fundamental importance was attributed, in that context, to duct associated histogenesis. A distinction was, therefore, made between ductal and ductular pancreas carcinomas. Invasive ductal carcinomas were subdivided by three categories: highly stromatous classical adenocarcinoma with poor prognosis, invasive ductal carcinoma with further differentiation (myxoma, squamous carcinoma, pleomorphous macrocellular and parvicellular types), and variations with specific differentiation (serous, mucinous tumours) with good prognosis. Invasive ductular carcinomas were subdivided by terminal non-papillary adenocarcinoma with protracted illness, ciliary adenocarcinoma, microglandular adenocarcinoma, ductulo-acinous tumour with excellent prognosis, and oncocytic carcinoma. These should be distinguished from intermediary cells with cellular transformation and neoplastic differentiation, such as adenocarcinoma with hepatocellular differentiation and mixed tumours (exocrine and endocrine) with alternatingly predominant cell spectra. Determination of prognostically differentiated tumours types is considered to be an indispensable prerequisite for adequately adjusted effective therapy. This appears to be the only approach which promises progress for the future. PMID- 2327183 TI - [Dihydralazine hepatitis. Morphologic and clinical criteria for diagnosis]. AB - 70 cases of acute dihydralazine-associated hepatitis with centrolobular or confluent necroses, registered in the files of the Berlin-Friedrichshain Institute of Pathology, between 1981 and 1985, were classified into 3 types of diagnostic probability for differential diagnosis versus virus hepatitis. Classification was conducted according to recommendations given by a working group of pathologists, specialised in liver pathology. 42 cases out of this material had come from Prenzlauer-Berg Hospital, Department of Infectious Diseases, and were re-examined under clinical aspects. 6 of them were discarded from evaluation. Type I proved to be of high diagnostic reliability, as was seen from 61% of all cases. Only 3 cases had to be discarded from that group and were associated with other drugs, such as halothane, methyldopa, and propranolol. The following clinical parameters proved to be of particular value for definite assessment of drug-induced hepatitis: time of exposure (for analysis of co medication), time of recovery, and re-exposure test. Only circumstantial evidence so far can be provided for all histological types to causative relationship between drug ingestion and hepatitis. Compliance with mandatory notification should be ensured in all cases, since suspicious cases are explicitly included. Higher sex-related disposition of women to drug-induced hepatitis was confirmed in our material, with the female-to-male ratio being 3:1. PMID- 2327184 TI - [Detection of Leu-M1 immunoreactivity in brain tissue and brain tumors]. AB - Immunohistochemical investigations were made of 170 tumours of the central nervous system, using anti-Leu-M1, with electron microscopy being used on 22 of them. At least focal Leu-M1 positive reactivity was established from 10 in 24 astrocytomas, four in 22 oligodendrogliomas, and 9 in 15 ependymomas. Unambiguous Leu-M1 positivity was recorded from 54% of Grade I gliomas and 20% of Grade II gliomas. Other malignant primary tumours of neuroepithelial origin as well as all meningiomas and neurinomas proved to be Leu-M1 negative. However, severe immunopositivity was exhibited in all cases by reactive cerebral tissue adjacent to tumours. Three of four carcinoma metastases were Leu-M1 positive. Investigations, using electron microscopy, have clearly shown that MMA positivity in reactive brain is associated primarily with extracellular space and with plasma membranes of gliocytes. No products of immune reaction were identified, on the other hand, not even ultrastructurally, from neoplastically dedifferentiated cells of anaplastic neuroepithelial tumours. This is likely to suggest that neoplastically transformed gliocytes are no longer capable of expressing lacto-N fucopentose III. It has proved helpful in distinguishing between the benign and malignant nature of a tumour. More observations along those lines might contribute to more knowledge on dedifferentiation of gliocytes. Also, in electron microscopy, MMA positivity of carcinomas proved to be associated with glycocalyceal material. PMID- 2327185 TI - [Gangliocytic paraganglioma of the duodenum. Case report with immunocytochemical characterization]. AB - Described in this paper are histological, electron-microscopic, and immunocytochemical findings recorded from a duodenal gangliocytic paraganglioma in a 21-year old man. The sessile polypoid tumor consisted of epithelial cells, neuroid spindle cells, and gangliocytic elements. Neurosecretory granules were detected by electron-microscopy in the epithelial cells. The neuroid spindle cells exhibited the ultrastructural feature of Schwann cells. The tumor was immunocytochemically characterized by the S-100-reactivity of the spindle cells and numerous PP-reactive epithelial cells. Gangliocytic paragangliomas of the duodenum are of benign behaviour and should be removed by local excision. PMID- 2327186 TI - [The pathologic anatomy of important forms of bacterial pneumonia]. AB - Postmortem examinations were conducted on 7,952 cases with acute inflammatory processes of respiratory organs, among them 452 adults, between 1949 and 1988. Bacteria had been responsible for 87.5%, of these pneumonia cases, including Klebsiella for 15.3%, Pseudomonas for 13.5%, staphylococci for 9.9%, pneumococci for 4%, streptococci for 3.9% and Haemophilus for 0.7%. Other bacterial species of lower pathogenicity were recorded from 24.4% of all individuals who had died with pneumonia and mixed bacterial flora from another 29.3%. Pneumococcal and streptococcal forms of pneumonia were predominant in untreated patients. Staphylococci and gram-negative bacteria were primarily recorded from inflammatory foci, following penicillin treatment. Macroscopic and microscopic peculiarities are discussed in greater detail, together with aspects relating to the pathogenesis of forms of pneumonia caused by different pathogens. PMID- 2327187 TI - Histopathological sinus node classification and its relation to coronary atherosclerosis using an atherometric system. AB - Studies were conducted into 100 consecutive subjects (autopsy material), 53 men and 43 women between 31 and 70 years old, who had died a natural death. The HUDSON-procedure was used for histopathological analysis of the cardiac conducting system (CCS). About 48 microscopic slides of each subject, including sinus node (SN) tissue, were inspected by 4 pathologists in a blind study. The findings were classified by 3 different groups according to histopathological data of the SN, viz. changes and distribution of P and T cells, stroma, artery, and innervation of SN. The 3 major epicardial branches of coronary arteries were prepared for morphometric studies by WHO standards. A digitizer coupled to a microcomputer LTEL (Cuba, IBM-compatible) was used for quantitative evaluation of atherosclerotic lesions (AL), and all data were subsequently processed on the same computer, using a statistical commercial package (Number Cruncher Statistical System) for results. An atherometric system was used and proved to be a properly standardized methodology, suitable to characterize AL in any vascular sector or group of patients. The most remarkable results were as follows: Three group classification was useful in estimating the association between pathomorphological data of SN and coronary atherosclerosis. The atherometric system proved to be a powerful tool to study and characterize atherosclerotic lesions in coronary arteries. PMID- 2327188 TI - [Histotopographic and morphometric studies of the intramural coronary arteries in the trabecula septomarginalis of swine and pigmy goats]. AB - Up to six arteries traverse from the interventricular septum to the M. papillaris magnus in the trabecula septomarginalis (moderator band) of swine and pygmy goat. Musculo-elastic intimal thickenings, many of them quite extensive, are recordable from along the entire length of all these intramural coronary arteries which are between 50 microns and 300 microns in diameter. The conclusion may be drawn from the results of morphometric analysis that coronary arteries undergo enlargement in response to increased intimal thickening and that such enlargement does not lead to narrowing of the lumen. Peculiarities in wall structure of the arteries in the trabecula septomarginalis are interpreted as adaptive processes of the vascular wall to the extraordinary stress on those vessels. PMID- 2327190 TI - [Symposium on organ and tissue transplantation. Novi Sad, 24 February 1989. Proceedings]. PMID- 2327189 TI - [The effect of calcium antagonist nitrendipine on the morphological picture of experimentally-produced myocardial injuries in rats]. AB - Malignant renal hypertension was induced to Wistar rats by means of two methods (Lorincz-Goracz and Rojo-Ortega-Genest procedures), and hypoxaemia was produced by application of two ligatures to an aortic segment, for two hours. The lesions caused by these experimentally established pathological conditions were analysed by the following criteria, after treatment with a Ca-blocking agent (Nitrendipine, Bayer, Leverkusen): Changes in systematic blood pressure; Histochemical detectability of myocardial and vascular lesions as a consequence of artificially induced hypertension and hypoxaemia; Assessment by means of the tracer technique (Ferrlecit, Nattermann, Cologne) of alterations to vascular permeability in small cardiac vessels of rats treated and not treated with the Ca blocking agent; Detection of lesions in small vessels of other organs, such as intestine, mesentery, and pancreas, in rats treated and not treated with the Ca blocking agent. This study has been conducted for the purpose of elucidating vascular lesions resulting from lasting hypertension and short-term hypoxaemia, with particular attention being given to effects of therapeutic intervention on morphological expression of vascular damage. The Ca-blocking agent had a favourable effect on vascular alterations due to long-term and short-term injuries, since the animals treated with Nitrendipine exhibited drop in blood pressure and developed very mild vascular lesions, if any. The cardioprotective action of Nitrendipine was readily obvious under the above experimental conditions. PMID- 2327192 TI - [New possibilities in kidney transplantation from live unrelated donors]. AB - The kidney transplantation, as a method of medical treatment, could not be developed faster in our country for many years. A number of demands for transplantation grows much faster than our modest capability. The similar, but in a rather smaller degree, this problem occurs in some other countries in the world. The main cause is: the organization of corpse collecting and the conservatism of doctors. The latter problem, in the countries of western hemisphere, is surpassed more easily by a doctor codex and a legal obligation that involves doctors actively in this process, which is not the case in our country. The organization of corpse collecting in some states of the USA is highly developed, but however it does not give sufficient number of organs for the cadaveric transplantation. New, additional possibilities are found: the taking of even organs (kidneys) from alive unrelated donors, spouses, which excludes the possibility of greed and gives, only in the USA, about 1.500 additional alive transplantations per year. The complementary medical attitude towards the increasing of number of cadaveric transplantations is: considerably freely taking of kidneys from cadavers without tissue compatibility, only with the compatibility of blood groups of ABO system. Since the immunological criteria, in our country, are very intensified by the Zagreb immunology group, e.g. from 75-100% for alive transplantation, or the minimum of 50% tissue compatibility for cadaveric transplantation, this old-fashioned attitude has considerably lowered the number of transplantations in our country.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327191 TI - [Transplantation of the kidney at the medical school in Novi Sad--3 years' experience of an interdisciplinary transplantation team]. AB - The interdisciplinary transplant team on Medical faculty--Novi Sad is formed at the beginning of the 1986, and first successfully cadaver binephrectomy was performed in April 1986, and kidneys was transported in Transplant Centre in Belgrade. The first human renal transplantation with cadaveric kidney was performed 20, May 1986, and result was excellent. The first human renal transplantation with living related kidney was performed 27, Sept 1986, and result also was excellent. During the last three years our transplant team performed 32 renal transplantations. cadaveric kidney transplantations - 25 living-related kidney transplantation - 6 kidney autotransplantation - 1 Our Concept and organisation of interdisciplinary transplant team in Medical Faculty- Novi Sad is the very efficacy model of organisation and at the same time the cheapest solution. In this paper we discuss our organization of human renal transplantation, and technique of donor-neprectomy (cadaveric and living-related) and cold perfusion of kidney with Collins solution. Our rules for implantation are shown as the Algorythm. At the end of this paper we present our results, based on three year's experience and list of the members of our interdisciplinary transplant team. PMID- 2327193 TI - [Kidney transplantation in the treatment of patients with end-stage renal failure]. AB - Renal transplantation has become an acceptable mode of therapy for patients with end-stage renal failure since the early 1960s. Retrospective study was done to analyze clinical results od 126 patients who received either living related or cadaveric kidney. The cumulative graft survival rate was 90% one year and 80% four years after living related kidney transplantation. The corresponding patient survival rate was 96% one year and 94% four years after transplantation. There were no significant differences in graft and patient survival regarding mode of immunosuppressive therapy. In cadaveric kidney transplantation graft survival after one year was 78% and patient survival ranged at 98%. Our results are comparable to those of other centers and we think renal transplantation is adequate therapy for most patients with end-stage renal disease. PMID- 2327194 TI - [Kidney transplantation in high-risk patients]. AB - Immunosuppression with Cyclosporine A in kidney transplantation, triple therapy (CyA + Imuran + corticosteroids) and plasmapheresis before and after kidney transplantation in high risk recipients (positive cytotoxic antibody, MLC at the level of non related persons), also in high risk patients (juvenile diabetes, patients over 50 years old). In 1988 we had done in our Centre, kidney transplantation in 52.8% (28: 53) in high and increased risk patients. Triple therapy with plasmapheresis before and after kidney transplantation (if the level of cytotoxic antibodies is over 15%) allows successful kidney transplantation in high risk kidney recipients. Patients with juvenile diabetes are also available kidney recipients with therapy and permanent regulation of blood sugar. The patients of the age group between 50-60 years should be considered as suitable for kidney transplantation. PMID- 2327195 TI - [Kidney transplantation in Croatia]. AB - This review first presents historical data regarding clinical kidney transplantation in the world and in Yugoslavia. The need for kidney transplantation in the Socialist Republic of Croatia is estimated to be 250 per year while 50-60 are performed annually. A total number of kidney transplantations performed in Yugoslavia amounts to about 750, the center in Rijeka being the most active with 427 transplantations performed till the end of unts to About 750, The center in Rijeka 1988. The long-term results of living related transplantations (85% two-year-survival) at our institution are better than those of cadaver kidney transplantations (58% two-year-survival). There is a great difference in graft survival after 1983 (23% 4-years-survival before 1983 and 79% 4-years-survival after 1983) owing to multiple factors. A special significance was attributed to the cadaveric explanation programme and possible modes of its improvement. PMID- 2327196 TI - [Possibilities in the practical use of computers in the selection of candidates for kidney transplantation]. AB - This paper points out some problems appearing in the selection of candidates for the cadaveric kidney transplantation treats basic issues regarding medical and other references important for making decision in the process of candidate selection, emphasizes the significance of data base for prepared candidates and presents the specific example of the applications of APLLE II C in the practice of the clinic for nephrology. The data for each candidate are grouped in two sections: A. PERSONAL DATA 1. Family name and surname 2. Year of birth 3. Place of residence 4. Address 5. Telephone number 6. Register number of case history 7. Date of enlisting B. BASIC MEDICAL DATA 1. Blood type 2. HLA tipization of tissue: A, B, C, DR 3. Cytotoxic antibodies 4. Urgency priority 5. Date of eventual previous transpl. 6. Special remarks This mode of Candidate selection provides the availability of all relevant data at one place: objectivity and high efficiency. Creation of such data base in every Yugoslav Kidney Transplantation Center would "at the time" mean the formation of YU Information System, thus providing a possibility of choice of the most appropriate cadaveric Kidney recipient on Yugoslav level at any time. PMID- 2327197 TI - [The size and suitability of blood vessels for transplantation into the knee of the dog]. AB - An investigation of the size and suitability for the transplantation procedures of the knee blood vessels was made in 20 adult dogs with 40 extremities using the technique of injection of the arterial network through the femoral artery with the mixture of the methacrylic resin (SIGMAL R "Galenika", Belgrade) and the red ink. When the polymerisation of injected methacrylic resin was completed the specimens were exposed to either chemical or biological maceration of the tissues. Thirty-five specimens were chemically macerated using either 30% solution of hydrochloride acid or 40% potassium hydroxide. With this method bones were also destroyed and only the methacrylic vascular cast remained unaffected. Five specimens were exposed to the biological maceration using the insects (Dermestes vulpinus). This method proved to be better as the bones elements were not destroyed which allowed more precise study of vessel relations and topography. Calibre of the arteries was measured using the micromethod MEBA (Zagreb) with the accuracy of 0.01 mm. The main arterial vessels of the knee joint on the medial side are aa. saphena, genus descendes (branches of the femoral artery, then a. genus descendens (branches of the femoral artery, then a. genus medialis (branch of the popliteal artery), and on the lateral side are a. caudalis femoris distalis, (branch of the femoral artery), a genus lateralis (branch of the popliteal artery) and recurrent branches of the a. tibialis cranialis. Calibre of the femoral and popliteal arteries was over 2 mm which means that they are suitable for macrosurgical sutures, while the calibre of all other arteries was under 2 mm, and it is concluded that they are suitable only for microsurgical sutures. PMID- 2327198 TI - [Transplantation of the meniscus in dogs--preliminary report]. AB - A preliminary investigation of the allogenic transplantation of the meniscus without the vascular bundle was carried out in 4 adult dogs with 8 knees. In one operation session on 2 dogs at 2 operative tables and with two operative teams an identical surgical procedure in general anaesthesia was done. A medial parapatellar incision of the knee was used, the medial capsule and the collateral ligament near its proximal insertion were severed. Explanted medial menisci were exchanged and the meniscus from the other dog was put in position of the explanted one and fixed with 3 tangentially placed sutures (posterior, medial and anterior) which were taken out through the capsule and teid extra-articularly; there was no immobilisation, and after 3 weeks the identical operation was done on the other knee. The animals were sacrificed 4-5 months after the operation, the knees were dissected and observed. In all 8 knees transplanted menisci were completely healed around their periphery, however their appearance was rather changed. They were narrower, thinner, and of different colour and consistency. The transplanted menisci were removed and conserved in 10% (formalin) for the further investigation. It is concluded that the allogenic meniscal transplantation without the vascular bundle is possible and that the further investigation of this problem is justified. PMID- 2327199 TI - [Incorporation of nonvascularized auto- and allotransplanted bone into the site of bone defects]. AB - It is generally accepted viewpoint that free bone grafts do not survive transplantation, that the incorporation of the autograft is faster and safer than the one of the allograft, and that the immunological processes disturb the process of revascularisation and reossification of the graft, although they stimulate the process of absorbtion. The process of graft incorporation into the host's bone was followed up in 8 dogs, i.e. 16 knees. In 10 knees the medial tibial condyle was replaced by autogenic implants made of patella, thickness of 6 8 mm. and fixed by Kirschner wire. The process of allograft incorporation was studied in 6 knees, where the medial tibial condyle was replaced by the donor's graft. The process of the graft incorporation was followed-up by x-ray studies and after sacrificing the animals during the interval starting from 2 months to a year since the operation had been performed, while in the allograft group the follow-up was during the interval starting from 1 up to 5 months. The obtained results point out that the incorporation of the bone grafts thinner that 1 cm happens within first 8-10 months after the operation. The process of incorporation during this period happens at almost the same speed in both groups. If there are no technical errors while implanting, practically all the grafts of this thickness will be incorporated into the host's bone, i.e. completely reosified and revascularized. The congruity of the joint and the rigidity of the fixation play the main role in the fate of the graft within the first months after the operation. PMID- 2327200 TI - [Degenerative arthritis of the knee joint after allotransplantation of the joint surface without immunosuppression]. AB - Degenerative arthritis of the knee joint after resurfacing of the knee with fresh osteochondral allograft occurs frequently and was noticed a long time ago. The main causes can be: incongruity of the joint, when the allograft slips so that its surface is out of normal line, inadequate internal fixation different methods of cartilage preservation which are lethal to cartilage, broken grafts as well as immunological reaction to the graft. The experiment was conducted on 5 dogs, i.e. 10 knees. As for operated knees, the medial tibial condyle was replaced by fresh osteochondral allograft taken from the other animal, without preservation, performing precise operative technique and rigid internal fixation. These allografts were followed-up by x-raying them and after sacrifying the animals. The following-up of the development of the degenerative process continued up to 6 months after transplantation. The obtained results point out all the attitudes concerning all the other arthroplastic procedures (such as the precise reconstruction of the joint surface and the rigid internal fixation) should be respected. In spite of this, degenerative arthritis still exists in some cases as the result of immunological reaction to the graft, the process which may start within 6 months after transplantation. PMID- 2327201 TI - [Specifics in the reconstruction of individual elements in replantation of the forelimb in dogs]. AB - The experiment was carried out on the four extremities of six, sexually mature dogs of a different race. Gradual reconstruction of the anatomic structures was performed as a single act after the section of the elements. To reach stability of the forearm we employed different osteosynthetic techniques and succeeded to reconstruct blood vessels, nerves, ligaments and the skin, afterwards. Numerous techniques of suturing material were used. The animals were sacrificed six months after being operated and were exposed to microscopic observation and histological analysis. The results obtained suggested the necessity of a firm osteosynthesis of the forearm bones, use of less traumatic suturing material for suturing both blood vessels and fasciculi when preparating nerves. PMID- 2327202 TI - [Revascularization of the forelimb in dogs]. AB - Revascularization of the forearm was performed on six mature dogs of a different race. Arteria mediana was cut 2 cm above the fork of the arteria radialis and later sutured with a nonresorptive monofilament thread/Ethilonr/7-0 and 8-0 in diameter. The same process was repeated on the cefalica vein. Arteriographies were performed on the operated extremities, pre-operatively, immediately after operation and while an animal being sacrificed. The subjects were sacrificed six months after the operation. Then microscopic and histological analyses were carried out to assess the quality of the blood vessels at the suturing place. At the place of the blood vessels reconstruction, lumen did not get narrower which indicated that all the vessels were in a perfect functional condition. In a number of dogs a higher collagenic proliferation was noticed, in the vicinity of the blood vessels sutured. In the regenerative process of the arterial wall tunica mediana almost took a predominant position, like in the intact arteria. All the three strata were present with no relevant deviations in structure. In the cefalica vein the regeneration of the connective tissue support of the smooth muscles cells was insufficient. Based on the analysis of the results obtained it might be concluded that after revascularization of the forearm of the dog the regeneration of the blood vessels made the segment functionally capable with the structure not different from the normal one which existed in the blood vessels of the same part of the body. PMID- 2327203 TI - [Multiorgan explantation]. AB - In this paper, we discuss an ALGORYTHM of multiorgan explantation, including strategy, alternate technical principles with especially circumstances during this surgical procedure and rules for functional evaluation of human organs during and after explantation. PMID- 2327204 TI - [Histologic changes in fascia lata transplants in the replacement of the anterior cruciate ligament of the knee in dogs]. AB - Lesions of the anterior cruciate ligament of the knee are very frequent misfortune and the results of their suture being insufficient yet, made us to explore the possibility to replace the damaged ligament with the fascia lata as an autologous transplant. Surgical operation was performed on dogs. Instead of the anterior cruciate ligament removed, we used a piece of a rolled fascia lata. Six months after transplantation being performed, samples of the fascia lata were extracted for histological analysis to assess their structure and to evaluate the transplant as a neoligament, on the basis of its similarity with the normal structure of the ligament. After degeneration of a part of transplant because of the insufficient supply of nutrients, the invasion of the synovial blood vessels into the fascia lata was established and the young granulation tissue formed on the account of the nondifferentiated adventitial cells. In the mosaic of the transplant structure there were present parts of a more mature, dense connective tissue with longitudinal orientation of the cells, the fibers and the vascular elements, which partially made structure similar to that in ligaments. In the attachment region fibrocartilage was noticed, gradually passing into the hyaline one, to merge with the hyaline cartilage of the joint surface. After the histological analysis follows the conclusion that fascia lata functionally could replace the anterior cruciate ligament if a role was supplied with sufficient collagenic fibers on the cross-section. Time is of a high importance, too.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327205 TI - [Personal experience with segmental corporo-caudal allotransplantation of the pancreas in an experiment on dogs]. AB - In the Institute for Surgery, its Experimental Centre, has already several years an experimental transplantations of pancreas been carried out with the aim of learning surgery technique and performing a clinical transplantation of that organ. In our work we have used a technique of corporacaudal allotransplatation of pancreas with vascular anastomosis. As the blood vessels of the graft we have used the arteria and vena lienalis with parts of aorta and portal vein, which have been anastomosed with a. and v. iliaca communis of the pancretotomized recipient. We have used techniques of the open pancreatic duct, ligated pancreatic duct, our own technique of permanent bleeding of the pancreatic graft during the transplantation pancreaticojejunostomy and pancreatico-vesicular anastomosis. As the parameters of function of allograft we are using: glycaemia, i.v. GT test, K constant, insulinaemia, amylasaemia, length of survival of animals and pathohistological finding. The average term of survival of experimental animals was 28 days. During the function of alograft the experimental animals shown some signs of laboratory subclinical diabetes. Refusal of transplant was followed by sudden increase of glycaemia, without any clinical or laboratory sign of anticipation of the refusal. PMID- 2327206 TI - [Partial heterotopic and total orthotopic transplantation of the liver in dogs]. AB - From 1983 to 1988 on the Department for Experimental Surgery 20 preservations of the liver has been done, with ice cold Euro- Collins and Ringer solutions, either with in situ or with on banch technique after fast expantation. On five dogs standard 55% left hepatectomy has been done and the right side preserved in situ. Partial heterotopic liver transplantation to the right iliac fossa was performed on five dogs. Total vascular exclusion of the liver and extracorporal inierior vena cava and jugular vein by pass with assisted circulation was performed on one dog, without assistance on four dogs. Total orthotopic liver transplantation was performed on two dogs. The surgical team practiced the technique of liver transplantation in experiment and liver resection with in situ technique and on banch technique. PMID- 2327207 TI - [Experimental study of liver allograft damage during cold ischemia]. AB - Changes on the majority of structural complexes were observed in livers that underwent the influence of the preservant and cold ischemia. Cellular architecture of a such liver is disturbed. Hepatocites are with granular and vacuolar degeneration: focal cariolyzes and piasmolyzes are present, partial destruction of cellular membrane is noticeable. The dilatation of sinusoidal spaces is very emphasized and followed by the severe loss of endothelium. These changes along with the disturbed cellular architecture represent the findings of Pelosis hepatis. It is important to emphasize the significance of changes observed on liver sinusoids and endothelium especially since their intensity is much greater than of those changes observed on parenchim. We assume that these angioarchitectural damages play an important role in the onset and development of cardiopulmonal and coagulopatic components of the postreperfusional syndrome. The fact that the postreperfusional syndrome was also observed in cases with heterotopic transplantation could support this assumption. PMID- 2327208 TI - [Damage in the hemato-enteral barrier in experimental liver transplantation]. AB - Semiquantitative analyzes of intestinal mucous lesion graduating from 0 (normal) to V (necrotic) were done in the experimental model, 6-12h alter the heterotopic liver transplantation in dogs. All degrees of mucous damages were found in intestinal samples (mean value was 2.60). The most dominant were the lesions of III (31%) and IV (25%) degree while in 4% complete destruction of mucousal villious was observed. Success of liver transplantation besides the presence of the lesions of hepatic alograft during the phases of the warm and cold ischemia or immunological responses, depends on the changes in functionally connected regions. In that sense the damages of mesenterial department lead a very important role. Lumenal infective agents and cardiodepressive macromolecules, passing trough the hematoenteral barrier, cause local hepatic damages and central cardiovascular failure. PMID- 2327209 TI - [Morphofunctional changes in potential liver allografts in experimental conditions]. AB - As a part of morphofunctional investigations of validations cadaveric grafts for transplantation evolution of the histomorphological changes was followed by the experiments on guinea pigs. Liver samples were immediately after sacrificing the animals and 1, 2, and 4h later and kept at body temperature, which corresponded to the conditions of "warm ischemia". Second group of samples was immerged in Saline are +4 degrees C (hibernation-preservation) and was taken for analysis in same intervals as previous ones. Evolution of morphological and enzymatic changes was evident in short interval after sacrificing the animals. First changes were observed in cytoplasm and then in nuclei and interestitum. Changes of hepatic cells from hibernation preservation group were significant damaged comparing with the corresponding samples obtained from cadaver. ("warm ischemia"). These preliminary results indicated that length of liver graft preservation is very limited. Furthermore, this results demand for the future investigations in different conditions of preservation. PMID- 2327210 TI - [Vascular aspects of experimental transplantation of the kidney in dogs]. AB - Organ transplantation is predominantly vascular surgical procedure. Vascular aspects of renal transplantation are important in all surgical phases of this procedure: --donor-nephrectomy (living-related or cadaver nephrectomy)--include nephrectomy undamaged kidneys, each with good length of renal artery (with or without aortic patch), renal vein (with or without caval patch) and ureter - organ-ex situ-surgery (bench surgery) sometimes is necessary after cold perfusion with Collins solution --implant surgical procedure, which include--dissection of recipient vessels (localisation.) --venous anastomosis (type and technique) - arterial anastomosis (type and technique) --use of vascular grafts (autografts or alografts) for kidney revascularisation during implantation (???) In the period 1987-1988, in our Experimental Surgery Unit a total of 20 dogs were operated (experimental kidney autotransplantation) under the same surgical team. The aims of those experimental autotransplantations were: training of the surgical team for routine human renal transplantations and usefulness of vascular grafts (autografts or allografts) for kidney revascularisation. We divided animals into the three groups: The first group (5 dogs)--revascularisation using AUTOVENOUS grafts The second group (5 dogs)--revascularisation using ALLOGRAFTS (Dacron or e PTFE-Goretex grafts) The third group (10 dogs)--direct revascularisation without vascular grafts (control group) The best results were in the third group (no early vascular thrombosis) especially with end-to-end arterial anastomosis (we prefer it) and end-to-side venous anastomosis. Unfortunately in the second group, results were bad (vascular anastomotic thrombosis in the all cases during the first 48 hours).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327211 TI - ["Ex situ" reconstruction of blood vessels of the renal hilus in experimental transplantation in dogs]. AB - The variations of arterial and venous hillar blood vessels in human kidneys are numerous and surgical transplant teams have to know them. It is very important during doner-nephrectomy for transplantation. Sometimes, after doner, nephrectomy and kidney cold perfusion with Collins, there is a need for vascular repair of kidney hillar blood vessels, using microvascular surgical technique. The aim of this repair is: to have a kidney with main renal artery of good length and size and with main renal vein of good length and size. This procedure is called: extracorporeal "ex-situ" vascular repair of kidney hillar blood vessels. In the period 1987-1988, in our Experimental Surgery Unit a total of 20 dogs were operated on (kidney autotransplantation) and only in four (4) dogs we found variations in numbers of kidneys arterial and venous hillar blood vessels (20%) and repaired those vessels after cold perfusion of kidney. One dog had kidney with double renal arteries and double renal veins, and we had to make fusion the both arteries into the main renal artery of good size (5 mm) and the both veins into the renal vein of good size (12 mm). Three dogs had kidneys with main trunk of renal artery and one important separate polar renal artery, and we had to make implantation of separate polar renal artery into the main trunk of renal artery (end-te-side vascular anastomosis). For those vascular reconstructions we used polipropilene 6-o or -o as suturae material and binocular (magnification 2.5 x). The hemodynamically results of those reconstructions immediately after kidney implantation were very satisfactory. PMID- 2327212 TI - [Substitution of the ureter with a segment of the major saphenous vein in dogs]. AB - In this preliminary experiment of the possibility of substituting an segment of ureter with a segment of the saphenous vein in dogs, authors are showing the histological changes on the veno-ureteric anastomosis and the normal morpho functional condition of the kidney. The experiment was performed on two adult male dogs. In both animals, the transperitoneal approach was used to reach the ureter, which was then liberated from the neighbouring structures in the length of approximately 5 cm. A segment of the ureter was then substituted with a segment of the saphenous vein, in the length of approximately 2 cm. The suture of the anastomosis was done with unresorptive material (Prolene 6/0). The suture went through the adventitions and muscular layers of the ureter and the venous wall. In the first dog after two, and in the second after four months after the operation, an intravenous urography was done. It showed undistorted kidney function, without significant morfological changes of the pyelocaliceal system and the ureter. Histoological analysis of the specimen, taken from the anastomosis, proved the vitality of the venous transplant. PMID- 2327213 TI - Erythropoiesis, serum erythropoietin, and serum IGF-I in rats during accelerated growth. AB - In this study we have examined the correlation between activity of erythropoiesis and serum concentrations of erythropoietin and insulin-like growth factor I in male and female rats during accelerated growth (day 30-90). We found that fractional incorporation of iron into newly formed red blood cells was linearily correlated with body weight gain. Total iron incorporation into newly formed red blood cells reflecting total daily red cell formation increased almost linearily between day 25 and 80 after birth in both sexes. While serum erythropoietin concentrations decreased in the time interval investigated (25-120 days), serum IGF-I levels increased in both sexes between day 25 and 55. In this period, individual values of total iron incorporation into red blood cells and serum IGF I concentrations were linearily correlated. Our observations support the concept that IGF-I rather than erythropoietin modulates erythropoiesis during accelerated growth and thus manages a proportional increase in body mass and oxygen transport capacity. PMID- 2327214 TI - Biphasic response of rat tibial growth to thyroxine administration. AB - To evaluate the dose-response relationship between thyroxine and tibial growth, 60 male rats age 21 days were rendered hypothyroid by administration of methimazole in the drinking water. Twenty-one days later, the hypothyroid rats were randomly divided into 5 groups which received 0, 2, 8, 32, or 64 micrograms.kg-1.day-1 of T4 im for 21 days. All animals were sacrificed at age 64 days. Rat tibia were removed for measurement of epiphyseal growth plate width and longitudinal growth rate. Serum T4 and IGF-I levels were determined by RIA. Methimazole therapy significantly decreased serum T4, IGF-I, epiphyseal growth plate width, and longitudinal growth rate compared to controls. Epiphyseal growth plate width gradually increased when T4 was administered at doses from 2 to 32 micrograms.kg-1.day-1 (271 +/- 14, 311 +/- 15 and 324 +/- 11 microns), and subsequently decreased when T4 was given at a dose of 64 micrograms.kg-1.day-1 (267 +/- 8 microns). A similar profile was observed for longitudinal growth rate and IGF-I. We conclude that rat tibial growth has a biphasic response to exogenous T4 administration, and that the effects of T4 on tibial growth may be mediated through IGF-I secretion. PMID- 2327215 TI - Erythrocyte-associated triiodothyronine in the rat: a source of hormone for target cells. AB - The accumulation of T3 by rat erythrocytes and its transfer to cultured rat hepatocytes were investigated. The amount of erythrocyte-associated T3 in whole rat blood was determined at 37 degrees C. The ratio of erythrocyte-associated T3 to plasma total T3 was 0.235 over a wide range of T3 concentrations, i.e. there is 25 times as much T3 in the erythrocyte compartment as free in the plasma. Influx and efflux of T3, which were shown previously to be carrier-mediated, proceeded rapidly (t 1/2 approximately 12-15 sec at 25 degrees C). These results suggest that erythrocytes are involved in the supply of T3 to target cells. This was checked by studying [125I]T3 uptake by cultured rat hepatocytes incubated either with erythrocyte suspensions pre-equilibrated with labelled T3 or with extracellular medium from the same erythrocyte suspensions. In protein-free medium, the initial velocity of T3 uptake was 1.5-fold faster in the presence of the erythrocyte suspension. Uptake was saturable, the apparent Km of T3 uptake (nmol/l) was 163 +/- 13 in the absence of erythrocytes and 102 +/- 6 in their presence. Vmax (fmol.min-1.well-1) was similar in both cases (477 +/- 26 and 511 +/- 20, respectively). In the presence of diluted plasma (1:16 dilution) and in the presence of the erythrocyte suspension, a 2-fold increase of initial velocity was obtained. Plasma by itself increased (4-5 times) the initial velocity of uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327216 TI - Kidney tissue insulin-like growth factor I and initial renal growth in diabetic rats: relation to severity of diabetes. AB - The initial renal hypertrophy in experimental diabetes is dependent on the prevailing blood glucose level and is associated with renal accumulation of insulin-like growth factor I. To investigate the relationship of blood glucose to kidney IGF-I, a graded range of diabetic aberration was established in young rats by iv injection of increasing amounts of streptozotocin (25-80 mg/kg) at day 0. In 30 diabetic rats the mean of day 1 and day 2 blood glucose concentrations ranged from 6.2 to 32.0 mmol/l and 24-h urinary glucose excretion (24-48 h) from 0.04 to 43.3 mmol/24 h. The right kidneys were removed after 48 h, weighed and their IGF-I concentration analysed by radioimmunoassay. Kidney IGF-I was positively correlated to blood glucose (r = 0.66, p less than 0.0001) as well as to 24-h urinary glucose output (r = 0.54, p less than 0.005). At this early stage, kidney weight already correlated to blood glucose (r = 0.60, p less than 0.0005). No relationship between kidney IGF-I and kidney weight was found. However, if animals with severe diabetes were excluded, a significant correlation could be established (r = 0.51, p = 0.01, N = 24). The results support the hypothesis that IGF-I plays a causal role in the initial renal hypertrophy of experimental diabetes. PMID- 2327217 TI - Lipolysis in isolated epididymal adipocytes from genetically obese Zucker rat treated with 3,5,3'-L-triiodothyronine. AB - Glycerol released by isolated epididymal adipocytes was measured in 6-8 weeks old genetically obese (fa/fa) and lean (C.c.a/-) male Zucker rats, ip treated or not treated with T3 (0.46, 2.3 and 4.6 nmol/100 g in a single injection or 4.6 nmol.(100 g)-1.day-1 for 5 days). In the non-treated rats, lipolysis was less stimulated by adrenalin or isoproterenol in obese than in lean rats, whereas it was stimulated by theophylline up to the same level in both kinds of rats. A single injection of the T3 (highest dose) increased isoproterenol-induced lipolysis in the lean but not in the obese rats. The 5-day T3 treatment caused a stimulation of the adrenalin- or isoproterenol-induced lipolysis in both kinds of rats. However, the stimulation was lower in the obese than in the lean rats. This treatment increased theophylline-induced lipolysis in the lean but not in the obese rats. It did not affect significantly the theophylline-induced lipolysis stimulated by adrenalin or isoproterenol in either obese or lean rats. These findings show that mild hypothyroidism of obese rat is partly responsible for the impaired sensitivity of its adipose tissue to lipolytic drugs. The apparently low T3 sensitivity of obese rat adipose tissue is discussed. PMID- 2327218 TI - Relaxin and prostaglandin on oxytocin secretion from bovine luteal cells during different stages of gestation. AB - The objective of this study was to determine whether bovine luteal cells from different stages of gestation secrete oxytocin and whether relaxin, cloprostenol (a potent analogue of prostaglandin F2 alpha), estradiol-17 beta, and LH can acutely alter oxytocin secretion. Bovine luteal cells (10(5)) were cultured for 24 h without treatment and with medium-hormone replacement every 24 h. Oxytocin was quantified by radioimmunoassay of the culture media. Basal oxytocin secretion was similar (22-31 pmol/l, p less than 0.05) for all stages of gestation (days 100, 145, 160, 185, 200, 210, and 240). Relaxin induced a dose-dependent suppression of oxytocin release. After 24 h of incubation, addition of 0, 16.7, 83.5, and 167 nmol/l porcine relaxin (3000 U/mg) induced 54 +/- 4, 105 +/- 16, 47 +/- 4, and 38 +/- 4 pmol/l of oxytocin in cells from 160-day-old corpora lutea and 138 +/- 12, 21 +/- 2, 19 +/- 3, and 15 +/- 2 pmol/l oxytocin in cells from 240-day-old corpora lutea. From luteal cells of 160- and 240-day-old corpora lutea, 2 micromol/l cloprostenol induced a marked increase (p less than 0.01) of 208 +/- 39 and 371 +/- 34 pmol/l oxytocin, respectively. Addition of 167 nmol/l relaxin did not prevent cloprostenol-induced oxytocin secretion during the first 48 h, but a decrease (p less than 0.05) in oxytocin occurred in day 3 cell cultures. These results indicate that cultured luteal cells obtained from different stages of gestation in cattle can secrete oxytocin and suggest a role for relaxin in the regulation of oxytocin release. PMID- 2327219 TI - Neuroendocrinological effects of ketoconazole in rats. AB - The effect of ketoconazole on steroid synthesis was studied in intact (sham operated) and castrated male and ovariectomized female rats. Rats were given 25 mg/kg ketoconazole twice a day im for 5 days. The influence of ketoconazole was also investigated on hormone release altered by GnRH, estradiol and haloperidol. The following hormones were measured: serum LH, PRL, testosterone, corticosterone, 17-OH-progesterone, estradiol, and dopamine content of the tubero infundibular area. Ketoconazole treatment resulted in a significant decrease of testerone level (from 7.93 +/- 1.99 to 3.83 +/- 0.94 nmol/l), whereas LH, PRL, corticosterone and 17-OH-progesterone remained unchanged in the male rat. The effect of castration on LH level was reduced by ketoconazole in male (from 590 +/ 35 to 390 +/- 25 micrograms/l) and female rats (from 468 +/- 22 to 346 +/- 39 micrograms/l), but the GnRH-stimulated LH release in castrated and ovariectomized animals was unchanged. The suppressive action of estradiol on LH in ovariectomized rats was enhanced (from 160 +/- 41 to 64.6 +/- 12.9 micrograms/l), and its priming effect on PRL release was diminished by ketoconazole (from 598 +/ 81 to 281 +/- 66 micrograms/l). Ketoconazole failed to modify the tubero infundibular dopamine content and haloperidol-induced PRL release. It can be assumed that in addition to its inhibitory role of steroid biosynthesis ketoconazole has an influence on central mechanisms underlying LH and PRL release. PMID- 2327221 TI - I am Gaylene. PMID- 2327220 TI - Growth hormone increases rate of pubertal maturation. AB - We have performed a retrospective analysis of the pubertal parameters of 134 children with isolated GH insufficiency on GH treatment and compared them to the standards of Tanner and to a recent longitudinal study of growth and development in the United Kingdom. The age at onset of puberty (13.0 years in boys, 12.1 years in girls) was found to be significantly delayed (Mann-Whitney p less than 0.001), but duration of puberty (1.5 years in both sexes) was shortened (Kolgomarov-Smirnov p less than 0.01). Skeletal maturity at the onset of puberty was not advanced excluding this as a contributory factor. There was no association between dose of GH administered and the pubertal parameters. The results suggest that GH accelerates the pubertal process. PMID- 2327222 TI - Clinical problem solving through research. PMID- 2327223 TI - A.A.R.N. position statement: the role of registered nurses in settings where registered nursing assistants are employed. PMID- 2327224 TI - 'Business' an alternative career in nursing. PMID- 2327225 TI - Quality assurance in the home care setting. PMID- 2327227 TI - Awareness and general anaesthesia. AB - A state exists after the induction of anaesthesia in which patients may be aware of their surroundings yet unable to communicate. This problem of awareness and recall during general anaesthesia is a recent one in the relatively short history of anaesthesia. Prior to the introduction of muscle relaxants in 1942 by Griffith and Johnson, it was felt that "light anaesthesia" would be signified by violent movements. Today, the concepts of anaesthetic depth, awareness, and recall have become more complicated with the addition of numerous newer, shorter-acting, intravenous anaesthetic agents with varying effects on the conscious state. Several methods have been described to detect awareness. None has yet been found to be totally reliable and numerous reports of awareness can be found in the literature. Light inhalation and total intravenous anaesthesia have been blamed for the majority of these case reports. However, awareness during total intravenous anaesthesia is avoidable with the proper use of a combination of a hypnotic and an analgesic such as midazolam and alfentanil for general anaesthesia. PMID- 2327226 TI - The use of midazolam in diagnostic and short surgical procedures in children. AB - A new technique of sedation for children is described, in which midazolam (0.2 mg.kg-1) was administered topically by the nasal route, followed by ketamine (9.0 mg.kg-1) administered rectally in 32 patients breathing air spontaneously. Sedation was good in 23, seven required further ketamine (1.0 mg.kg-1 i.v.), and in two, halothane was introduced. There was no evidence of severe respiratory depression except during oesophagoscopy. Cardiovascular stability was excellent. Of 21 patients over 5 years old, 19 developed complete and two partial anterograde amnesia for the administration of ketamine and surgery. The major complications were nausea and vomiting (five patients) and salivation (eight patients). The mean recovery time was 40 min (s.d. 33 min). It provided a relatively safe, adaptable, non-invasive method of inducing sedation in children. PMID- 2327228 TI - Immunoglobulin-mediated activity against red blood cells in the saliva of amyotrophic lateral sclerosis (ALS) patients. AB - Immunoglobulin (Ig)-mediated activity in plasma directed towards normal blood type matched red blood cells (RBC) inducing haemolysis in vitro has earlier been demonstrated to be a characteristic feature in ALS-patients. In this study, saliva of ALS-patients, normal and diseased controls was tested with the same in vitro test. An increased degree of haemolysis was induced by the ALS-patient as compared with control samples. The activity thus found in saliva had the same basic characteristics as that earlier described for plasma; it reacted similarly to serial dilution and was retained in salivary Ig. The effect on red blood cells of saliva from patients with bulbar paralysis was larger than that of saliva from ALS-patients lacking bulbar symptoms. It is discussed whether cytotoxic Ig in saliva could be pathophysiologically active in bulbar paralysis by means of passage through the oral mucosa and local action on motor end plates in perioral muscles. PMID- 2327229 TI - CNS involvement in Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy. AB - Thirteen consecutive Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were studied by MRI, evoked potentials, and EEG. We found 3 of these patients exhibited symptoms of CNS disorders. Of these 3, 2 with abnormal MRI and visual evoked potentials, and one with abnormal brainstem auditory evoked potentials were detected. Another case without clinical CNS signs showed abnormal EEG findings. The subclinical CNS abnormalities found in the Japanese patients were considered to be less frequent than in cases from Western countries reported previously. PMID- 2327230 TI - Orthostatic tremor: essential and symptomatic cases. AB - We studied clinically and electrophysiologically 8 patients affected by orthostatic tremor (OT), which is an unusual movement disorder consisting of shaking movements of the legs and trunk in the standing position. We failed to find any cause in 6 of the 8 cases. In 2 patients OT was clearly secondary to neurologic disease: hydrocephalus due to non-tumoral aqueduct stenosis and chronic relapsing polyradiculoneuropathy. The findings obtained suggest a relationship between OT and essential tremor (ET). PMID- 2327231 TI - Subacute cerebellar syndrome as the first manifestation of AIDS dementia complex. AB - A patient presented with a subacute cerebellar syndrome in absence of cognitive impairment or other symptoms. He became demented several months after the onset of the disease. Necropsy demonstrated the typical features of the AIDS dementia complex and severe loss of Purkinje cells of the cerebellum. Patients with subacute cerebellar dysfunction should be evaluated for the presence of human immunodeficiency virus infection. PMID- 2327232 TI - Skin nerve sympathetic activity reflex latency in Parkinson's disease. AB - Using a microneurographic method, skin nerve sympathetic activity (SSA) reflex latency was measured in 16 patients suffering from idiopathic Parkinson's disease (PD) and 11 age-matched normal subjects. The mean latency in patients with PD was significantly delayed (0.821 s, p less than 0.01), when compared with that in normal subjects (0.676 s). Reflex latency showed a significant positive linear correlation with arm length. By determining the SSA reflex latency, conduction velocities in post-ganglionic skin sympathetic nerve were measured indirectly. Averaged conduction velocities in PD and normal subjects, 1.76 m/s and 1.86 m/s, respectively, did not differ significantly (p greater than 0.1). This data suggests that the reflex pathway of SSA is disturbed in patients with PD and that the increased reflex latency is caused by a central/preganglionic delay. PMID- 2327233 TI - Epidemiology of adverse reactions to carbamazepine as seen in a spontaneous reporting system. AB - A survey was made of 505 reports on 713 adverse reactions to carbamazepine submitted to the Swedish Adverse Drug Reactions Advisory Committee from 1965 1987. For the period after 1972, the relation between the reports and sales statistics could be investigated. The total incidence of reported adverse reactions to carbamazepine was 4.5 per million defined daily doses (DDD), corresponding to 2.7 per million prescribed daily doses (PDD). Most often reported were skin reactions (48%), but reports on haematological (12%) and hepatic disorders (10%) were also frequent. Virtually all hepatic disorders and severe skin reactions, as well as the majority (60%) of the haematological reactions, occurred within the first 2 months of treatment. In view of the very low incidence of reported serious blood dyscrasias, such as pancytopenia (0.04/million PDD) and agranulocytosis (0.06/million PDD), continuous haematological monitoring seems to be of little value. The elderly appear to be at increased risk of developing blood dyscrasias and liver reactions, and alcohol abusers seem to represent a high-risk group for developing serious skin reactions. PMID- 2327234 TI - Cognitive impairment in amyotrophic lateral sclerosis and its relation to motor disabilities. AB - The performance of patients with amyotrophic lateral sclerosis (ALS) on selective neuropsychological tests was examined in regard to the applicability of such examinations to diagnosis. Eighteen patients with ALS, and 15 age- and education matched controls were given a battery of tests designed to assess motor and intellectual functions. The ALS group displayed significantly lower scores on all tests than those in the control group. Correlation analyses on the several motor and neuropsychological results in ALS group revealed that there was a significant negative correlation between upper motor symptoms and mini-mental state examination, as well as memory tests. PMID- 2327235 TI - Nervous system manifestations in Sjogren's syndrome. AB - Central and peripheral manifestations of the nervous system were evaluated in 48 Sjogren's syndrome patients. Fifty-six percent of the patients had neurological disturbances. The most common manifestations were entrapment neuropathies (19%) and polyneuropathy (15%). Electrophysiological tests gave further evidence of subclinical nervous system involvement in Sjogren's syndrome: electroencephalography (EEG) was abnormal in 48%, and visual evoked potentials (VEP) in 12% of patients tested. To find possible neuropsychiatric abnormalities, the Minnesota Multiphasic Personality Inventory was applied, and 33/43 patients were found to have psychiatric symptoms. The most frequent were depressive symptoms. In 44% of the patients there was additional evidence of extraglandular involvement or autoimmune disorders. No correlation could be found between the groups of patients with or without neurological disturbances in relation to simultaneous occurrence of associated disorders. It is suggested that nervous system involvement in Sjogren's syndrome reflects the pathogenetic consequences of Sjogren's syndrome alone, and not those of associated autoimmune diseases of extraglandular disorders. PMID- 2327236 TI - Clinical and electrodiagnostic findings in breast cancer patients with radiation induced brachial plexus neuropathy. AB - The clinical and neurophysiological characteristics of radiation-induced brachial plexopathy (RBP) were assessed in 79 breast cancer patients without signs of recurrent disease at least 60 months after radiotherapy (RT). Clinically, 35% (95% confidence limits: 25-47%) had RBP. Fifty percent (31-69%) had affection of the entire plexus, 18% (7-36%) of the upper trunk only, and 4% (1-18%) of the lower trunk. In 28% (14-48%), assessment of a definite level was not possible. In most, symptoms began during or immediately after RT, thus being without significant latency. Numbness or paresthesias (71%, 52-86%) and pain (43%, 25 62%) were the most prominent symptoms, while the most prominent objective signs were decreased or absent muscle stretch reflexes (93%, 77-99%) closely followed by sensory loss (82%, 64-93%) and weakness (71%, 52-86%). Neurophysiological investigations were carried out in 46 patients (58%). The most frequent abnormalities in patients with RBP were signs of chronic partial denervation with increased mean duration of individual motor unit potentials, and decreased amplitude of compound muscle and sensory action potentials. Nerve conduction velocities were normal. PMID- 2327237 TI - Methyl bromide myoclonus: an electrophysiological study. AB - We report a case of myoclonus from overnight exposure to methyl bromide. Myoclonus was either spontaneous or induced by somatosensory stimulation or voluntary movements, multifocal and sometimes generalized. Median SEP showed normal size P14-N20, but giant parietal P25, N33 and frontal P22-N30 waves. Back averaging showed a biphasic EEG spike of maximal amplitude at the central region contralateral to the corresponding myoclonic jerk recorded from abductor pollicis brevis and preceding it by a short interval consistent with conduction in corticospinal pathways. Long latency reflexes from cutaneous and mixed nerve stimulation were enhanced. The above electrophysiological findings suggest that myoclonus following methyl bromide poisoning belongs to the cortical reflex myoclonus category. PMID- 2327238 TI - Therapeutic intervention in mentally retarded adult epileptics. AB - Clinical features of epilepsy, especially those connected with drug therapy, were evaluated for mentally retarded adult epileptics who were admitted to the neurological out-patient unit during 1977-83. These features were re-evaluated in 1985 and compared with findings from the first visit. During follow-up, the type and frequency of seizures were determined and if possible, medical therapy was either concluded or changed. The therapeutic intervention resulted in the use of fewer and less toxic drugs, for which the serum concentrations were more often within recommended ranges. These aspects may be due to the significant decrease in seizure frequency observed. In order to provide patients with the most efficacious therapy, the therapeutic needs of mentally retarded adult epileptics should be evaluated by a neurologist familiar with epilepsy. PMID- 2327239 TI - Vinconate prevents ischemic neuronal damage in the rat hippocampus. AB - The neuroprotective effect of vinconate, a novel vinca alkaloid derivative, was examined in a rat model of forebrain ischemia induced by 4-vessel occlusion. Hippocampal cell loss was quantified histologically 3 days after 10 or 15 min of ischemia. Intraperitoneal application of vinconate (25 and 50 mg/kg) 10 min before and immediately after 10 min of ischemia significantly reduced the neuronal cell loss in the CA1 sector of the hippocampus. Protective effect of vinconate against 15 min of ischemia was reduced, but there was still significant protection at the higher dose. Autoradiography using 14C-vinconate showed that the drug easily penetrates the blood-brain barrier and distributes in the hippocampus. The result suggests that vinconate prevents ischemic neuronal damage by direct action on the hippocampal CA1 neurons. PMID- 2327240 TI - "To hundred and twenty4our": a study of transcoding in dementia. AB - The ability to transcode integers from ideographic to alphabetic script was assessed in patients with dementia of Alzheimer type. Eleven of 13 consecutive patients made characteristic errors of intrusion. We propose that this may be a simple bedside test for dementia. PMID- 2327241 TI - Signs of Sjogren's syndrome in a patient with myasthenia gravis. AB - A case of myasthenia gravis (MG) with recurrent submandibular salivary gland enlargement and focal lymphocytic infiltrates in lip salivary glands is described. Though the clinical and close histopathological resemblance with Sjogren's syndrome (SS), a condition characterized by impaired exocrine function of affected glands, no exocrine disturbance evolved during 3-years follow up. The clinical and histopathological overlap between MG and SS, sharing several immunological characteristics, might be of relevance in further studies on the pathogenesis of the two conditions. PMID- 2327242 TI - White matter lucencies in multi-infarct dementia: a somatosensory evoked potentials and CT study. AB - White matter low attenuation (WMLA) on computed tomography (CT) and the central conduction time (CCT) measured by median nerve-somatosensory evoked potentials were examined in 12 multi-infarct dementia (MID) patients, 10 patients with multiple infarcts (MI) without dementia and 11 age-matched controls. Patients with deep vascular lesions without cortical infarcts on CT were included. In MID, prolongation of CCT and moderate to severe WMLA were observed. The CCT and WMLA in MI patients were intermediate. The CCT was longer when the WMLA was more extensive. The result suggests that white matter disease in MID is concerned to the occurrence of dementia by disturbing axonal conduction. PMID- 2327243 TI - Lesch-Nyhan syndrome with delayed onset of self-mutilation: hyperactivity of interneurons at the brainstem and blink reflex. AB - We studied a case of Lesch-Nyhan syndrome with delayed onset of self-mutilation. Athetotic cerebral palsy and mental retardation were diagnosed at 1 year old, but the disease was not suspected until age 8 years when he began biting his lips and fingers. There was no obvious alteration of catecholamine in urine and CSF. We attempted to induce a series of blink reflexes by electric, mechanical and photic procedures. The R1 amplitude increased and the latency of the R2 shortened compared with controls. This shows that not only orbicularis motoneuron itself, but also uncrossed interneurons, are in a state of hyperexcitability. The contralateral R2 was poor which was in favour of hypoexcitability of the crossed interneurons at the brainstem. The significant large response was obtained by photic procedure which was in favour of hyperexcitability of the motoneurons. Therefore, it is demonstrated that a thorough examination of blink reflexes provides a useful method for examination of a state of the underlying neural activity. PMID- 2327244 TI - Penicillamin-induced neuropathy in rheumatoid arthritis. AB - A case of penicillamin-induced severe polyradiculopathy in rheumatoid arthritis is presented. The neuropathy was of demyelinating type, purely motor, proximal and clinically fully reversible when the drug ceased. In case of a progressive neuropathy, during penicillamin treatment, this adverse effect should be born in mind, and discontinuation of the drug considered. PMID- 2327245 TI - Mixed solvent exposure and cerebral symptoms among active and retired workers. An epidemiological investigation of 3387 men aged 53-75 years. AB - In an epidemiological study comprising 3,387 men aged 53 to 75 years, 3303 men with valid questionnaire answers to questions on occupational organic solvents exposure, four cerebral symptoms and current work status were examined. Two hundred and ninety-five men had been occupationally exposed to mixed organic solvents for a period of 5 years or more. Among them 178 were retired, while 117 were still gainfully employed. The exposed men in both groups had highly significantly more complaints of decreased concentration ability and of memory difficulties. Of the exposed retired men a higher prevalence of headache was found. Among the exposed still employed a trend towards a higher prevalence of dizziness was found. This study was conducted within a cardiovascular study with no focus on the relationship between organic solvent exposure and cerebral symptoms, a design reducing the risk of overreporting. If overreporting was responsible for the differences found between solvent-exposed and unexposed cases a similar pattern for reporting of acute and chronic symptoms should be expected. This was not the case. Our results support the hypothesis, that occupational exposure to organic solvents for a period of 5 years or more increases the risk of developing persistent memory difficulties and a decrease in concentration ability. PMID- 2327246 TI - Prominent white matter lesions develop in Mongolian gerbils treated with 100% normobaric oxygen after global brain ischemia. AB - Carotid arteries were occluded bilaterally for 15 min in two groups of Mongolian gerbils. The first group received 100% oxygen during the first 3 h of reperfusion. During that period, room air was given to the second group. After 3 h, both groups received room air. Brains of gerbils that died within 14 days after occlusion were removed, fixed in formalin and embedded in paraffin. Gerbils that survived 15-28 days were perfused with formalin before their brains were removed and embedded in paraffin. Adjacent, serially cut sections were stained with luxol fast blue (LFB)-H&E, cresyl violet, according to the Bodian method, or immunocytochemically with antisera raised against myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP). In brain sections of gerbils receiving 3 h of 100% oxygen, there were circumscribed white matter lesions in the corpus striatum, lateral thalamus, mesencephalon and posterior limb of the internal capsule. Myelin sheaths were swollen, fragmented and were less intensely stained by MBP antiserum. MBP and LFB-stained myelin fragments were present extracellularly and in macrophages. Many axons in these areas appeared undamaged. Previously described ischemic changes were found in gray matter and some areas of white matter in both groups. However, neurons in the deeper laminae of the cerebral cortex appeared to be better preserved in gerbils given oxygen. The results suggest that hyperoxia, if present immediately after transient brain ischemia, may damage myelin more severely than other cellular elements. PMID- 2327247 TI - Three-dimensional structure of Alzheimer's neurofibrillary tangles of the aged human brain revealed by the quick-freeze, deep-etch and replica method. AB - The three-dimensional structure of Alzheimer's neurofibrillary tangles in the pyramidal cells of the hippocampus and in the nerve cells of the parahippocampal gyrus was examined by the quick-freeze, deep-etch and replica method. The tangles consisted of either parallel bundles of or randomly arranged paired helical filaments (PHF), occupying the perikaryotic cytoplasm and extending to the dendritic processes. On the stereophotographs the PHF, measuring 28 to 36 nm in width, had two component filaments of 14 to 18 nm in diameter which were coiled anti-clockwise (left-handed) around each other with periodicity of 70 to 90 nm. The PHF in compact parallel bundles were cross-linked to each other with thin filaments, of about 6 nm in diameter, at relatively regular intervals. Randomly arranged PHF had no cross-bridges or side arms. Straight-type tangles of about 24 nm in diameter were rarely found in the dendritic processes. There were no discernible differences between the PHF of the patients with senile dementia of Alzheimer type and those of nondemented brains. PMID- 2327248 TI - Neuronal damage following non-lethal but repeated cerebral ischemia in the gerbil. AB - Brief, non-lethal transient forebrain ischemia in the gerbil can injure selectively vulnerable neurons when such ischemia is induced repeatedly. The influence of the number and interval of the ischemic insults on neuronal damage, as well as the time course of damage, following repeated 2-min forebrain ischemia were examined. A single 2-min ischemic insult caused no morphological neuronal damage. A moderate number of hippocampal CA1 neurons were destroyed following two ischemic insults with a 1-h interval, and destruction of almost all CA1 neurons resulted from three or five insults at 1-h intervals. Three and five insults also resulted in moderate to severe damage to the striatum and thalamus, depending on the number of episodes. Although three ischemic insults at 1-h intervals caused severe neuronal damage, this number of insults at 5-min and 4-h intervals caused destruction of relatively few neurons, and no neurons were destroyed at 12-h intervals. Following three ischemic insults at 1-h intervals, damage to the striatum, neocortex, hippocampal CA4 subfield and thalamus was observed at 6-24 h of survival, whereas damage to the hippocampal CA1 subfield appeared at 2-4 days. The results indicate that even a brief non-lethal ischemic insult can produce severe neuronal damage in selectively vulnerable regions when it is induced repeatedly at a certain interval. The severity of neuronal damage was dependent on the number and interval of ischemic episodes. PMID- 2327249 TI - Regional impairment of protein synthesis following brief cerebral ischemia in the gerbil. AB - Regional cerebral protein synthesis following brief ischemia was investigated in the Mongolian gerbil, utilizing L-[methyl-14C]methionine autoradiography. Transient ischemia was induced for 1, 2 or 3 min. At various recirculation periods up to 48 h, animals received a single dose of L-[methyl-14C]methionine and then were terminated 35 min later. Sham-operated animals showed a normal pattern of amino acid incorporation into the proteins of the brain. Following 1 min ischemia, the pattern of protein synthesis was similar to that in the sham operated gerbils. Ischemia for 2 min, however, caused marked inhibition of protein synthesis in the neocortex, striatum, hippocampal CA1 sector and the thalamus at 1 h of recirculation. Extensive recovery of protein synthesis was found in the neocortex, the striatum, the hippocampal CA1 sector and the thalamus at 5-24 h of recirculation, but, a slight inhibition was detectable in the hippocampal CA1 sector in one of six animals. This inhibition had fully recovered at 48 h of recirculation. Following 3-min ischemia, severe impairment of protein synthesis was found in the neocortex, striatum, the whole hippocampus and the thalamus. After 5-24 h of recirculation, the protein synthesis in these regions had gradually recovered, except that complete lack of amino acid incorporation was seen in the hippocampal CA1 subfield. This impairment of protein synthesis in the hippocampal CA1 sector was not recovered at 48 h of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327250 TI - Contrary effect of lactic acid on expression of neuron-specific enolase and glial fibrillary acidic protein in human glioma cells. AB - We examined the effect of lactic acid on cultured human glioma cell lines expressing glial fibrillary acidic protein (GFAP), vimentin and neuron-specific enolase (NSE). The growth of the cells was inhibited by the lactic acid in a dose dependent manner. At 56 mM of lactic acid, the surviving cells of the KNS-42-c2 cell line developed slender processes and increasingly formed bizzar giant cells. In an immunofluorescence study of the lactic acid-resistant cells, the GFAP positive cells prominently decreased in number, while the NSE-positive cells clearly increased. The vimentin was not affected throughout the experiment. After removing lactic acid from the medium, the GFAP-positive cells gradually increased in number. The method of dot immunoassay was useful for quantifying GFAP in cellular extracts. It indicated that the amount of GFAP decreased in the cells cultured with lactate-containing media and increased to the primary values after removing the lactic acid. These results may suggest that the morphological and immunochemical diversities of glioma cells are secondarily affected by cellular microenvironments such as lactic acid. PMID- 2327251 TI - Acute response of the fetal telencephalon to short-term maternal exposure to ethanol in the rat. AB - Pregnant rats were exposed to either ethanol (total dose 18 g/kg) on gestational days 14 and 15 or whole-body ionizing radiation (0.5 Gy) on gestational day 15. On gestational day 16, 24 h following the last dose of ethanol or exposure to ionizing radiation, the developing cerebral cortex of the fetus was examined histologically. Ionizing radiation caused extensive cell death within the fetal cerebral cortex whereas ethanol caused more subtle morphological changes such as cortical thinning and petechial intraventricular hemorrhages. These findings suggest that ethanol, unlike ionizing radiation, acts by some mechanism other than cell death to cause cortical thinning and cortical malformations. The pathogenesis of ethanol-induced cortical dysgenesis may include fetal hypoxia and inhibition of neuroblast proliferation within the developing cerebral cortex. PMID- 2327254 TI - [Polarographic determination of diaveridine in biological samples]. AB - Differential pulse polarographic method was applied for determination of diaveridine in plasma, whole blood and isolated organs (liver, spleen, kidney, thymus). Deproteinization of homogenized blood and organs had been carried out on Extrelut column and then concentration of diaveridine was determined by measuring peak current at EP = -1100 mV peak potential on pulse polarogram in 10(-3) mol/dm 3 perchloric acid. The developed procedure--which has been validated by gas chromatographic method--has been suitable to determination of acid concentrations and pharmacokinetic curves. PMID- 2327252 TI - Cross-reactivity of monoclonal antibody Leu-19 with some neuroectodermal and other non-immune tissues. AB - Leu-19 antigen is a 200-220 kDa surface glycoprotein, initially detected on natural killer (NK) cells exhibiting non-major histocompatibility complex restricted cytotoxicity. Using a monoclonal antibody (mAb) directed against the Leu-19 molecule, we were unable to identify NK cells immunohistologically in cryostat sections of neuroectodermal tumors. Instead, mAb Leu-19 cross-reacted with the surfaces of the tumor cells, except for melanomas. It stained mesodermal tumor cells less intensely and did not stain those of carcinoma metastases. In three plasmacytomas, cells were observed, most likely NK cells, which extend Leu 19-positive cell processes towards to the unstained tumor cells. Furthermore, the Leu-19 antigen was identified on physiological tissues, especially on all neuroendocrine cells analyzed. The cross-reactions observed with Leu-19 mAb were confirmed using mAb NKH-1, which is also directed against the Leu-19 molecule. Thus, the expression of Leu-19 on neuroectodermal cells is another example of antigen sharing between specialized immune cells and the nervous system. PMID- 2327253 TI - Electron-dense lipidic capillary deposits in Rett syndrome. AB - Conjunctival, muscle, and peripheral artery biopsies were examined by light and electron microscopy in a patient with clinically diagnosed Rett syndrome. In capillaries, amorphous and membranous electron-dense deposits were observed (a) endoluminally attached to endothelial cell membranes, (b) within junctional clefts of adjacent endothelial cells, and (c) at abluminal sites of endothelial cells. In addition, electron-dense deposits lay isolated or inside multivesicular bodies in endothelial cells and pericytes. These findings have not been reported before in Rett syndrome. They were not seen in age-matched normal or pathological control cases and are suggested to indicate deposition of an as yet unknown lipidic plasma component possibly in association with impairment of the blood tissue barrier. PMID- 2327255 TI - [Rheologic investigation of electrode gels. III. Study of temporal changes of gel structure]. AB - In the publication consisting of 3 parts nine electrode gels have been investigated siu of them are used in hospital pharmacies of this country. Character and stability of gel structure have been studied and controlled by rheological methods. Structural forces have been numerically characterized with maximum and equilibrium viscosity, values of "M and B coefficients" and directional tangents of viscosity curves. Mechanical and thermal stability have been determined, changes for six months storing have been studied by means of all rheological parameters, respectively. Besides investigating rheological parameters electric conductivity values--which are important in respect of practical use of electrode gels--have been determined too. On the basis of results Carbopol "G" designated gel has been found to be the best its use has been proposed not only in supersonic tests but also in ECG. PMID- 2327256 TI - Production and investigating of tablets containing furosemide and beta cyclodextrin. AB - Furosemide is a very active drug with an excellent saluretic effect, but it dissolves in water only with difficulty. Furosemide products with beta cyclodextrin (CD) have been made by five methods, and it has been established that most drugs are liberated most quickly from the kneaded product for the 12.72% combinations. The dissolution characteristics of furosemide are improved in tablets made from the kneaded product. By this means an essentially quicker effect can be achieved, a lower drug quantity is necessary for a similar effect, a smaller therapeutic risk in involved, and the technique is economical too. PMID- 2327257 TI - [Hydrophobic constant values (delta RMO) of functional groups. II. Interpretation of fragment interactions]. AB - The delta RM0(-CH2-) values have been calculated from fragment values of various alkyl groups (methyl, ethyl, n-propyl). On the basis of delta RM0(-CH2-) values it has been established that the value of the so-called "second" methyl group from aromatic ring has slightly differed from that of the so-called third methylene group and the value of methylene functional group is constant independently from positions of substituents and from electronic interactions. The delta RM0 Me values of methyl group--which is directly attached to aromatic ring--have been regarded as the so-called first methylene group from aromatic ring since value of free energy needed for transfer of methyl group as well as the other physico-chemical data (mole volume, parachor) are nearly the same as those of methylene group according to the literature. Fragment values of methyl groups substituted at various positions have been compared to relating delta RM0( CH2-) value which is free practically from electronic interactions and it has been ascertained that fragment values have been higher as well as lower. In accordance with literature lower delta RM0 Me values have been interpreted with hyperconjugation effect of aromatic system. On the other hand lower methylene fragment values of alkyl substituted compounds at N1 atom have been attributed to sigma conjugation. In literature higher delta RM0 Me values than relating delta RM0(-CH2-) value are known only in case of orto position to another functional group or by a methyl group on a sterically hindered aromatic ring. Results of tests have shown that values of delta RM0 Me can substantially increase with extension of conjugated aromatic system or with simultaneous substitutions of methyl, methylene groups, respectively at certain locations. The authors have assigned that increase to change of solvate cuver which surrounds the molecule. The same has been manifested by methyl fragment values of quinazoline derivates (tetrahydropyrroloquinazoline, hexahydroazepinoquinazoline) of different electronic distributions. On basis of calculations it has been proved that delta RM0 2-Me and delta RM0 6-Me fragment values of monosubstituted pyrido (1,2-a) pyrimidine (PP) derivatives have significantly differed from delta RM0 Me values of at other positions (3,7,8,9) methyl substituted compounds. Among disubstituted derivatives only delta RM0 7-Me and delta RM0 8-Me values of 2-phenyl- and 3 carbetoxymethyl-PP derivatives have not differed from each other but methyl fragment values of other positions (6,9) have significantly differed from each other and from other fragment values too.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2327258 TI - Cardiovascular and metabolic responses to static contraction in man. AB - There is substantial controversy regarding muscle blood flow and its regulation during static exercises. Major issues include (1) the relationship between developed force and muscle blood flow, (2) the ability of metabolic vasodilation to overcome neurally mediated vasoconstriction, (3) the time course and magnitude of hyperaemic flow following static exercise and (4) blood flow to the contralateral inactive limb. At rest, 15, 25 and 50% maximal voluntary contractions (MVC) femoral venous flow in four healthy young men (LBF; mean +/- 1 SD) was 0.4 +/- 0.3, 1.76 +/- 0.65, 0.90 +/- 0.32 and 1.06 +/- 0.59 1 min-1, and mean arterial pressures (MAP) were 104 +/- 13, 140 +/- 14, 160 +/- 17 and 161 +/- 11 mmHg. Thus, LBF does not increase proportionally with increasing levels of MVC, despite increased arterial pressure. Further, during both 25 and 50% MVC, which were held to exhaustion, an elevated limb vascular resistance was encountered towards the end of contraction, which suggests that neurally mediated vasoconstrictor activity overrides local vasodilation. Femoral venous effluent documented perfusion of active muscle during contractions of 15 and 25% MVC, but less so at 50% MVC. Immediately in recovery LBF reached levels of 3-3.5 1 min-1, which corresponded to 150 ml 100 g-1 min-1. When both O2 uptake and lactate release during the contractions and in recovery were taken into account, a close correlation between rate of energy turnover and exerted force was found. When MAP was raised by static contraction of the opposite quadriceps, LBF in the inactive leg increased momentarily. Within 1 min vascular resistance became elevated and the blood flow became reduced. PMID- 2327259 TI - Muscle carnitine metabolism during incremental dynamic exercise in humans. AB - The changes in muscle content of carnitine and acetylcarnitine have been studied during incremental dynamic exercise. Six subjects exercised for 10 min on an ergometer at 40 and 75% of their maximal oxygen uptake (VO2 max) and to fatigue at 100% of VO2 max (about 4 min). Muscle samples were taken from the quadriceps femoris muscle at rest and after exercise. Muscle content of free carnitine was (means +/- SE) 15.9 +/- 1.7 mmol kg-1 d.wt (dry weight) at rest and remained unchanged after exercise at low intensity but decreased to 5.9 +/- 0.6 and 4.6 +/ 0.5 mmol kg-1 d.wt after exercise at 75 and 100% of VO2 max respectively. Acetylcarnine content at rest was 6.9 +/- 1.9 mmol kg-1 d.wt and increased during exercise in correspondence with the decrease in free carnitine. Muscle content of pyruvate and lactate was unchanged after exercise at 40% of VO2 max but increased at the higher intensities. The parallel increases in acetylcarnitine, pyruvate and lactate indicate that formation of acetylcarnitine is augmented when the availability of glycolytic three-carbon metabolites is high and is consistent with the idea that acetylcarnitine provides a sink for pyruvate and acetyl CoA. This could be of importance for the maintenance of an adequate level of CoA and thus function of the tricarboxylic acid cycle. PMID- 2327260 TI - Force and EMG signal patterns during repeated bouts of concentric or eccentric muscle actions. AB - Healthy males (n = 14) performed three bouts of 32 unilateral, maximal voluntary concentric (CON) or eccentric (ECC) quadriceps muscle actions on separate days. Surface electromyography (EMG) of the m. vastus lateralis (VL) and m. rectus femoris (RF) and torque were measured. Integrated EMG (IEMG), mean (MPF) and median power frequencies and torque were averaged for seven separate blocks of four consecutive muscle actions. Torque was greater (P less than 0.05) for ECC than for CON muscle actions at the start of exercise. It did not decline throughout ECC exercise, but decreased (P less than 0.05) markedly for each bout and over bouts of CON exercise. Thus, torque overall was substantially greater (P less than 0.05) for ECC than for CON exercise. At the start of exercise IEMG of VL or RF was greater (P less than 0.05) for CON than for ECC muscle actions. This was also true for overall IEMG activity during exercise. The IEMG increased (P less than 0.05) modestly for both muscles during each bout of CON or ECC muscle actions, but did not change for the VL over bouts. The IEMG of RF decreased (P less than 0.05) modestly over CON but not ECC exercise bouts. At the beginning of the first bout of exercise the IEMG/torque ratio was twofold greater (P less than 0.05) for CON than ECC muscle actions. The ratio of IEMG/torque increased (P less than 0.05) markedly during CON but did not change during ECC exercise. Thus, by the end of the third bout there was a fivefold difference (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327261 TI - Effect on cortical blood flow of electrical stimulation of trigeminal cerebrovascular nerve fibres in the rat. AB - It has recently been demonstrated in the rat that the majority of cerebrovascular pain fibres containing immunoreactive substance P and calcitonin gene-related peptide reach the vessels via the nasociliary nerve, a branch of the ophthalmic trigeminal division. In order to elucidate the effect of these nerves on blood flow in vivo, the relative changes in cortical microvascular flow were continuously monitored by a laser-Doppler flowmeter system during electrical nerve stimulation, with the central nerve connection cut and after removal of neighbouring dilatory parasympathetic nerves. The nasociliary nerve on one side was stimulated proximal to the ethmoidal foramen by a bipolar platinum electrode. Activation at different frequencies, continuously or as bursts with a constant voltage, impulse duration and total stimulus length, revealed that a maximum increase in blood flow amounting to 16.7% after 36 s was obtained with continuous stimulation at 10 Hz. Flow markedly declined during the following 1-min stimulation period. No changes in contralateral cortical blood flow, mean arterial blood pressure or blood gases were observed during or after stimulation. The present study demonstrates for the first time that direct and selective electrical activation of trigeminal cerebrovascular nerves induces an increase, albeit small and transient, in blood flow within the brain. PMID- 2327262 TI - Influence of splanchnic intravascular volume changes on cardiac output during muscarinic receptor stimulation in the anaesthetized dog. AB - The direct influence of systemic muscarinic receptor stimulation on total splanchnic intravascular volume and the splanchnic organs responsible for the total splanchnic volume change associated with muscarinic receptor stimulation in the animal with an intact circulation are unknown. Furthermore, the subsequent effect of these volume changes on cardiac output is not known. Thus, acetylcholine was infused at 5 micrograms kg-1 min-1 in 25 anaesthetized dogs in which nicotinic blockade of the ganglia was achieved with mecamylamine, while total and regional splanchnic intravascular volume changes were determined with a radionuclide imaging technique. Total splanchnic volume decreased by 4.9 +/- 1.0% (P less than 0.0001), splenic volume decreased by 10.3 +/- 2.0% (P less than 0.0001), hepatic volume increased by 5.8 +/- 1.4% (P less than 0.01), extrahepatosplenic volume increased by 6.6 +/- 1.6% (P less than 0.01) and cardiac output increased from 1960 +/- 190 to 2290 +/- 230 ml min-1 (P less than 0.001). After splenectomy (n = 13), the hepatic and extrahepatosplenic volume increments were abolished, and the increase in cardiac output was not attenuated (1600 +/- 260 to 2040 +/- 370 ml min-1). After subsequent evisceration (n = 5), the cardiac output increment associated with acetylcholine was still not attenuated. Acetylcholine-associated splanchnic volume changes were abolished after muscarinic receptor blockade with atropine. Thus, muscarinic receptor stimulation causes a decrease in total splanchnic volume due entirely to a decrease in splenic volume. The splanchnic volume changes do not influence cardiac output. PMID- 2327263 TI - Regulation of splanchnic organ size during muscarinic receptor stimulation in the anaesthetized pig. AB - To determine the mechanisms responsible for changes in splanchnic organ size during muscarinic receptor stimulation, acetylcholine was infused at 5 micrograms kg-1 min-1 in 11 anaesthetized pigs which had previously undergone carotid denervation and cervical vagotomy. Blood pressure decreased by 42 +/- 4 mmHg (P less than 0.005), portal vein pressure decreased by 1.0 +/- 0.3 mmHg (P less than 0.01), IVC pressure increased by 0.2 +/- 0.1 mmHg (P less than 0.01), hepatic arterial flow increased by 10 +/- 6 ml min-1 (NS), portal vein flow decreased by 89 +/- 20 ml min-1 (P less than 0.005), splenic segment length (SSL) decreased by 0.52 +/- 0.11 mm (P less than 0.005) (control 12.49 +/- 1.27) (measured with ultrasonic crystals) and hepatic segment length (HSL) increased by 0.29 +/- 0.06 mm (P less than 0.005) (control 13.94 +/- 1.16). Aortic constriction to decrease the splanchnic distending pressure by an amount comparable to that achieved with the acetylcholine-associated decrease in portal flow caused a similar decrease in SSL and increase in HSL. Graded constriction of the portal vein or IVC, to increase SSL or HSL respectively, in the presence and absence of acetylcholine demonstrated no change in splenic or hepatic compliance with acetylcholine. Ligation of the splenic vasculature reduced the acetylcholine-associated HSL increase from 0.41 +/- 0.09 to 0.20 +/- 0.07 mm (P less than 0.05). Acetylcholine infused directly into the portal vein did not alter HSL. Atropine abolished all acetylcholine-associated haemodynamic changes. Thus, muscarinic receptor stimulation does not appear to act directly on splanchnic capacity vessels. Splenic dimension decreases due to a decrease in splanchnic flow and pressure, and hepatic dimension increases due to an increase in IVC pressure and redistribution of volume from the spleen. PMID- 2327264 TI - A study in the maintenance phase of ischaemic acute renal failure in the rat. AB - The fate of the trapped deformed erythrocytes seen in the early recirculation phase after ischaemia and the generation of long Tamm-Horsfall (TH) cylinders in the renal medulla during the first week after recirculation was studied in rats. In an in-vitro study the effects of different concentrations of TH protein on the permeability to Na+ of a semipermeable membrane were also investigated. The trapping of erythrocytes was found to be a reflow phenomenon, as there was no increase in the capillary area of the medulla in kidneys subjected to ischaemia but with no recirculation. This area increased to a maximum of 34.6 +/- 2.07% 20 min after recirculation and decreased to a normal value of 3.3 +/- 0.74% 1 day after the primary ischaemia. The area occupied by cylinders increased to a maximum of 19.2 +/- 1.4% 2 days after the primary damage and was as large as 16.7 +/- 1.47% after 1 week. It was also shown that the diffusion half-time of Na+ ions across a semipermeable membrane increased from 11.4 +/- 0.45 min to a maximum of 32.2 +/- 2.19 min with a protein concentration of 1 mg ml-1. It was concluded that the trapping of erythrocytes alone could not explain the decrease in renal function 1 week after the primary damage, but that the blockade of the tubules by the long homogeneous TH cylinders could be responsible for this decrease. PMID- 2327265 TI - Resetting of the pressure range for blood flow autoregulation in the rat kidney. AB - Both a myogenic response and the tubuloglomerular feedback control mechanism seem to be involved in autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF). Earlier experiments have shown that clamping of renal arterial perfusion pressure, below the autoregulatory range, reduces single-nephron GFR, and that this low value is maintained during the first 10-15 min after release of the clamp. It was also found that the tubuloglomerular feedback mechanism in the early declamp phase was strongly activated to reduce GFR. These findings can not be easily understood with the current knowledge of autoregulation, but would suggest a resetting of RBF and GFR autoregulation to a new level. To test this, left renal arterial perfusion pressure was reduced from 100 to 60 mmHg during 20 min with and without angiotensin converting enzyme inhibition (0.5 mg i.v. enalapril). Renal blood flow was measured with laser-Doppler flowmetry. When arterial perfusion pressure was reduced from 100 to 60 mmHg for 20 min, RBF was reduced to 77% of control and remained at this low level during the first minutes of declamp. In this situation there was an autoregulation to a new level. Renal blood flow was then slowly normalized (16.1 min). In the enalapril-treated animals RBF was only reduced to 85% during the 20 min of clamping and returned immediately to the control level at declamp. Thus, these experiments demonstrate that if renal blood flow is decreased by reducing the perfusion pressure below the normal autoregulatory range the pressure range for blood flow autoregulation resets to a lower level and that this change is mediated via the renin angiotensin system. PMID- 2327266 TI - Transport of serotonin from the rat jejunal lumen into mesenteric veins in vivo. AB - The transport of labelled (hot) and non-labelled (cold) serotonin (5-HT) into the mesenteric venous circulation was studied after instillation of test solutions into an isolated jejunal loop of anaesthetized rats. After instillation of [3H]H2O and [14C]5-HT there was an almost parallel appearance of the isotopes in mesenteric venous blood. After instillation of 5-HT a marked early increase of the total amounts of cold 5-HT was observed in mesenteric veins compared with animals instilled with saline only. In a third type of experiment the label was detected in mesenteric venous whole blood after instillation of [3H]5-HT into the gut lumen. After hydrolysis of blood cells and protein precipitation the samples were fractionated and determined for 5-HT and metabolites. Only 5-HT was detected in these fractions. The label was present within 5-HT peaks in three out of eight animals. The experiments indicate rapid transport of 5-HT (or metabolites) across the rat jejunal mucosa. These substances may be bound to a binding protein in platelets since the isotope was detected in whole blood but more seldom in supernatants after hydrolysis and precipitation. PMID- 2327267 TI - Urinary bladder and urethral responses to pelvic and hypogastric nerve stimulation and their relation to vasoactive intestinal polypeptide in the anaesthetized dog. AB - The effects on the urinary bladder and urethra of pelvic and hypogastric nerve stimulation and their relation to vasoactive intestinal polypeptides (VIP) were investigated in the anaesthetized dog. Both pelvic and hypogastric nerve stimulation elicited a twofold increase in urinary bladder blood flow and a clear cut increase in bladder venous effluent VIP concentration. Hypogastric nerve stimulation induced an initial, partly alpha-adrenergic and partly non adrenergic, non-cholinergic, contraction of the urinary bladder followed by a relaxation. The urethra response was a maintained alpha-adrenergic contraction. Pelvic nerve stimulation elicited a bladder contraction with an initial non cholinergic peak, whereafter the bladder pressure was maintained at a lower level, an effect which was mainly cholinergic in origin. The urethral response was an initial non-adrenergic, non-cholinergic contraction followed by a maintained cholinergic contractile response. Afferent pelvic nerve stimulation led to an efferent activity that seemed to be a combination of activity in pelvic and hypogastric pathways to the urinary bladder and the urethra. VIP (10 nmol) injected i.v. induced a relaxation of the urinary bladder and the urethra, together with a fall in systemic blood pressure. However, despite high plasma concentrations, no vasodilation was elicited in the urinary bladder. Thus, the main target for the VIP release during pelvic and hypogastric nerve stimulation is probably not the bladder vasculature, but instead perhaps the bladder smooth muscle proper. PMID- 2327268 TI - Simultaneous measurement of cytosolic free Ca2+ in macula densa cells and in cortical thick ascending limb cells using fluorescence digital imaging microscopy. PMID- 2327269 TI - Nicotine counteracts midbrain dopamine cell dysfunction induced by prefrontal cortex inactivation. PMID- 2327270 TI - Calcitonin gene-related peptide stimulates irregular spiking and transit of contents in the small intestine of the rat. PMID- 2327271 TI - Psychometric properties of the Manchester Scale. AB - This article reports a preliminary investigation of the psychometric properties of the Manchester Scale (MS). Fifty-three patients were assessed on the instrument, 33 at time 1 (7-10 days after admission) and 53 at time 2 (during the week prior to discharge). Interrater reliabilities were generally good at time 2. The factor analyses conducted on the 8 MS items at times 1 and 2 suggest that MS contains a heterogeneous group of items: only the MS negative symptoms were related to one another. The MS positive and negative symptoms were strongly correlated with their counterpart items on the Schedules for the Assessment of Positive Symptoms and Negative Symptoms, suggesting that the MS items have good concurrent validity. PMID- 2327272 TI - Reduced performance in tests of memory and visual abstraction in seamen exposed to industrial solvents. AB - Eighty-five seamen exposed to a variety of organic solvents and hydrocarbon compounds during their work on chemical tankers were compared with 59 unexposed seamen. Visual memory, auditory memory and visual abstraction were examined 14 days or more after the last solvent exposure. Multivariate analyses were performed to control the effects of confounding factors such as age, alcohol consumption, smoking, cerebral concussions and educational level. Significant correlations were found between increasing solvent exposure and poor results in tests of auditory memory and visual abstraction. These results indicate adverse psychological effects caused by chronic organic solvent exposure. PMID- 2327273 TI - The dexamethasone suppression test and completed suicide. AB - The present study was undertaken to further explore the relationship between the dexamethasone suppression test (DST) and suicide. Depressed inpatients who had undergone the DST at index admission and later committed suicide (n = 13) were matched for age, gender, diagnosis, and type of DST (1 mg, 2 mg) with depressed inpatients from the same hospital and study time period to form 2 groups: a suicide attempter group (n = 25) and a nonattempter group (n = 28). The suicide completers group had significantly higher 1600 postdexamethasone cortisol levels than the suicide attempters group and a significantly higher 1600 rate of DST nonsuppression compared with the suicide attempter + nonattempter combined group. Although the rate of DST nonsuppression did not differ between the suicide attempter and nonattempter groups, serious attempters had significantly higher 1600 cortisol levels and a statistically higher proportion of patients who completed suicide than nonserious attempters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327274 TI - Limitations of the Mini-Mental State Examination in predicting neuropsychological functioning in a psychiatric sample. AB - The present study examined the ability of the Mini-Mental State Examination (MMSE), a cognitive screening test commonly employed in research and clinical applications, to predict level of performance on a comprehensive neuropsychological battery, the Luria-Nebraska Neuropsychological Battery (LNNB). The tests were administered to a diagnostically mixed sample of 90 psychiatric inpatients. Correlations between the tests were statistically significant but modest and the MMSE was not able to detect many patients who demonstrated significant deficits on the LNNB. Additional correlational analyses between the MMSE and the Wechsler Adult Intelligence Scale-Revised in a subset of patients (n = 72) also showed a modest relationship between these instruments. The results suggest that the MMSE may seriously underestimate cognitive impairment in samples exclusively composed of psychiatric patients, making it inappropriate to rely solely on this instrument to distinguish psychiatric patients with and without cognitive deficit. PMID- 2327275 TI - Slower theta activity over the midfrontal cortex in schizophrenic patients. AB - Disturbances of the topographical distribution of theta activity in the EEG spectra before and during voluntary movements were investigated in 31 neuroleptic treated and in 13 untreated schizophrenics and matched controls as well as in 15 normals medicated with haloperidol. All 4 groups demonstrated similar topographical distribution of theta mean power density, with highest values over the midfrontal region. In the center frequency of the theta band, however, treated and untreated schizophrenics had lower values over the midfrontal region than at parietal electrodes. In controls and normals medicated with haloperidol, this frontoparietal "gradient" demonstrated the inverse picture, with highest values at the frontal midline electrode. Patients and controls differed significantly in this gradient. The slower theta activity over the midfrontal cortex in the schizophrenic patients is related to the hypofrontality hypothesis. PMID- 2327276 TI - Seasonal mood variation: an epidemiological study in northern Norway. AB - In an epidemiological study carried out in the town of Tromso in northern Norway an extensive questionnaire was sent twice, in summer and winter, to 1000 subjects to investigate the degree of symptoms of mood variation (depression or hypomania) during the polar winter night and midnight sun seasons. The results suggest that the general population north of the Arctic Circle shows a major seasonal mood variation. It is suggested that seasonal mood variation is a chronobiological mood disturbance related to and probably precipitated by extreme variations in light. The therapeutic implications and preventive measures are discussed. PMID- 2327277 TI - The availability of firearms and the use of firearms for suicide: a study of 20 countries. AB - The availability of firearms in a country was measured by noting the percentage of homicides committed using a firearm. This measure of gun availability was found to be positively associated with the suicide rate using firearms and negatively associated with the suicide rate using all other methods. The implications of these findings for suicide prevention are discussed. PMID- 2327278 TI - Psychiatric morbidity among mothers attending well-baby clinic: a cross-cultural comparison. AB - The Self Reporting Questionnaire (SRQ), a screening instrument developed for psychiatric disorders in developing countries, was administered to 149 mothers, half of whom where non-white, attending a well-baby clinic in Manchester, United Kingdom. Psychiatric interview confirmed that high scorers on the SRQ could be given DSM-III diagnoses of anxiety and depression, but the cut-off point on SRQ for being a definite psychiatric case was found to be 7/8, higher than previous validation studies. This was the same for Asians as well as white mothers. Comparison of somatic versus psychological scores between Asian and white mothers showed no significant difference across the range of total SRQ scores. Over half of the mothers who were psychiatric cases were attending their doctors and all the Asian women doing so were attending for somatic symptoms. This study suggests that when measured in a well-baby clinic, somatic and psychological symptoms are reported equally frequently by white and Asian immigrant women in the United Kingdom but somatic symptoms predominate when Asian women consult a doctor. PMID- 2327279 TI - Risk factors for aggressive behaviour are of limited value in predicting the violent behaviour of acute involuntarily admitted patients. AB - Violent behaviour within 8 and 28 days respectively was related by a multivariate statistical procedure to risk factors for aggressive behaviour in an epidemiologically representative sample of 105 acute involuntarily admitted patients. Previous violent behaviour by the patient was found to correlate significantly with aggressive behaviour during the first 8 days of admission, and abuse of drugs other than alcohol was found to correlate significantly with aggressive behaviour during the first 28 days of admission. Determination coefficients were very low, and it is concluded that risk factors associated with aggressive behaviour are of limited value in predicting aggressive behaviour among acute involuntarily admitted inpatients. PMID- 2327280 TI - Suicidal thoughts during early adolescence: prevalence, associated troubles and help-seeking behavior. AB - A total of 1600 adolescents between the ages of 13 and 16 living in a county bordering on Paris were interviewed concerning their health, their use of drugs, both legal and illegal, their behavior, and their seeking of health care. Fourteen percent of the boys and 23% of the girls had already thought about suicide and 5% and 10% (respectively) proclaimed having thought about it frequently. Young adolescents who thought about suicide, the girls as well as the boys, had more health problems (fatigue, nightmares, insomnia), used more drugs (including tobacco, alcohol, illegal drugs, psychotropic medicine) and had more delinquent behavior (robbery, running away from home, racketeering). Furthermore, the girls had problems in school (absenteeism and being left back). In general, youngsters with suicidal thoughts resorted to violence in a variety of ways. Although these youngsters spoke less readily about their personal problems, they more frequently sought physical health care (doctors, nurses, social workers). This discrepancy between their difficulty in communication and their readiness to ask for physical care is a clear indication of their need to be helped. PMID- 2327281 TI - The changing pattern of suicide by gassing in Australia, 1910-1987: the role of natural gas and motor vehicles. AB - There have been large changes in the use of gas as a suicide method in Australia during this century, the most marked being the increased use of motor vehicle exhaust fumes, and the introduction of natural gas in the early 1960s. In males, use of motor vehicle exhaust fumes as a suicide method has substituted for use of domestic gas. It was concluded that in neither sex did the elimination of toxic carbon monoxide in domestic gas, with the introduction of natural gas, result in a lasting reduction of suicide rates. Attention is drawn to possible failed suicide attempts using motor vehicles with emission controls, resulting in serious cerebral damage. PMID- 2327282 TI - Attempted-suicide trends in Stockholm County, Sweden, 1975-1985. AB - A total of 22,961 admissions, representing 19,127 individuals, diagnosed as certain or undetermined attempted suicide were registered in the computer medical information system in Stockholm County for the study period 1975-1985. Two different statistical regression models were used to describe the trends of attempted suicide and undetermined attempted suicide. A simple linear ordinary least squares model generally performed better at describing the observed rates in sex- and age-specific rates of attempted suicide when the diagnosis of attempted suicide was certain. Significantly increasing attempted-suicide trends for men over 35 and women over 45 as well as for all ages pooled for both men and women were found. Undetermined attempted suicides were described better by a quadratic model than by the linear model. Women 35-44 and 65-85 years old and men 25-54 years old were found to have an increasing initial phase followed by a leveling out in the rates around 1980-1982, with weak evidence that the rate might even be slowly decreasing. Comparing earlier findings of decreasing rates in completed suicides for all ages, and findings in this study of increasing attempted-suicide trends during the same period, we believe that improved somatic and psychiatric treatment of attempted-suicide patients may partly account for the decreased rates of completed suicides. PMID- 2327283 TI - Depressive type and state effects on personality measures. AB - We examine the hypothesis that the effect of mood state on personality questionnaire scores is more a function of diagnosis than of depression severity. Sixteen endogenous and 83 neurotic depressives completed a battery of personality questionnaires at a baseline assessment and again 20 weeks later. Scores on the personality measures changed significantly. Endogenous depressives were found to have more pronounced changes on measures of dependence and timidity, but when change in mood state was partialed out only one of the dependence measures and timidity remained significant. Thus the hypothesis only received partial support- change in mood state appears to be the major factor in elevating personality questionnaire scores. PMID- 2327284 TI - Premenstrual depression predicts future major depressive disorder. AB - To assess the power of premenstrual changes as a risk factor for future major depressive disorder (MDD), we conducted a follow-up study of 36 women who had volunteered for menstrual cycle studies. Scores on the depressive subscale of the Premenstrual Assessment Form (PAF) at initial evaluation were found to be significantly correlated (r = 0.35) with the occurrence of MDD during the follow up period. Moreover, multiple regression analysis indicated that the PAF scores had predictive value above and beyond 2 known risk factors for MDD, family history of depression and prior personal history of depression. The Premenstrual Change Index, a score derived from prospective daily self-ratings of severity of dysphoric symptoms, was also correlated with interval MDD, but did not enhance the predictive power of the PAF score. We conclude that the assessment of premenstrual depression has validity in identifying women at risk for future MDD, even when a retrospective instrument, PAF, is utilized for such assessment. PMID- 2327285 TI - Premenstrual changes. PMID- 2327286 TI - The effects of intrauterine growth retardation on the structural development of cranial nerves (optic, trochlear) in fetal sheep. AB - A quantitative morphometric study of the development of myelinated fibres in the optic and trochlear nerves has been made in growth-retarded fetal sheep at 140 days gestation (term = 146 days). Intrauterine growth retardation was induced as a result of the reduction of placental mass, by prior removal of placentation sites in six ewes. In the optic nerve (central nervous system) the mean diameter of myelinated fibres was not significantly reduced but the thickness of the myelin sheath relative to axon diameter was disproportionately reduced. In the trochlear nerve (peripheral nervous system) there was a significant reduction of 23% (P less than 0.01) in the mean diameter of myelinated fibres; however the normal axon:myelin ratio was maintained. The total number of myelinated fibres in the trochlear nerve did not differ between the normal and growth-retarded group, indicating that there was not a greater than normal incidence of cell death during intrauterine growth retardation in the nucleus of the trochlear nerve. The differential effect of intrauterine growth retardation on myelination in the central and peripheral nervous systems suggests that chronic intrauterine deprivation affects oligodendrocyte activity but does not markedly affect the capacity of Schwann cells to produce myelin. PMID- 2327287 TI - Glial-conditioned medium and attachment to ConA are essential for long-term culture of cortical neurons. AB - Cortical brain cells from 14-day-old mouse embryos were seeded on various substrates and cultivated in serum-free medium with or without conditioned medium from astrocytes or C6 glioma cells. Poly-L-lysine was shown to be the best substrate for cell attachment followed by Concanavalin A (ConA) and adhesion particles derived from glia cells. Cells grown on ConA sprouted rapidly and formed large networks. Survival of neurons was greatly prolonged when glia conditioned medium (GCM) was present in the culture medium. Cells grown on ConA were then viable for more than 4 weeks. Without GCM, neurons survived in culture for about 2 weeks, regardless of the substrate. Endothelial cell growth supplement or acidic fibroblast growth factor increased survival of neurons but also stimulated proliferation of astrocytes. PMID- 2327288 TI - ADP-ribosylation of proteins in brain regions of rats during postnatal development. AB - Post-translational modifications of chromatin-bound proteins play an important role in the regulation of eukaryotic gene expression. Processes such as acetylation, methylation, phosphorylation and ADP-ribosylation may alter the interaction of these proteins with DNA and consequently affect chromatin conformation and the binding of enzymes and other molecules involved in the regulation of gene expression. In the present study the process of ADP ribosylation of chromosomal proteins (histone and non-histone proteins) in some rat brain regions during postnatal development was investigated; also the effect of epidermal growth factor (EGF) on this process in fetal brain slices was studied. It has been found that the process of ADP-ribosylation of total histones extracted from rat cerebral cortex and cerebellum at 1, 10 and 30 days of age, increases from 1 to 10 days of age (i.e. the period of maximal cell proliferation) and decreases thereafter, while the process of ADP-ribosylation of non-histone proteins (NHPs) sharply decreases during the same developmental period. The addition of EGF to fetal brain slices causes a significant increase of ADP-ribosylation of total histones (particularly of the histone H1 fraction) and also of NHPs and microsomal proteins. This result is in agreement with the effect of EGF as a mitogen factor, previously shown in astroglial cell cultures. PMID- 2327289 TI - Calcium and calmodulin levels in late embryonic and early hatched Japanese quail brain. AB - Characterizing the last phases of embryonic avian brain development are increased brain activity and increased absorption of shell calcium. The calcium-binding protein, calmodulin, regulates many activities of calcium. In neural tissue, calmodulin modulates neural transmission, and is required for the phosphorylation of synaptosomal proteins. Therefore, the objective was to compare levels of brain calcium and calmodulin in the Japanese quail. Brain extracts from embryonic days 11, 15, hatch, and 5 days post-hatch (n = 7/group) were analysed for calcium, protein and calmodulin. Despite increases in protein between embryonic (X = 0.126 and 0.145 mg/mg wet wt) and hatched groups (X = 0.183 and 0.221 mg), no significant increases in calmodulin were observed (237-279 ng/mg protein). Calcium levels in the brain were U-shaped with low levels at embryonic day 1 (341 micrograms/mg wet wt) and post-hatch day 5 (315 micrograms/mg wet wt) with higher levels on embryonic day 15 (425 micrograms/mg wet wt) and at hatch (433 micrograms/mg wet wt). Calmodulin levels do not show a developmental pattern similar to calcium and protein levels or with reports of brain activity. PMID- 2327290 TI - Cerebral endothelial cell-derived laminin promotes the outgrowth of neurites in CNS neuronal cultures. AB - The aim of the present study was to elucidate whether the endothelial cells, besides providing the structural basis for the blood-brain barrier (M. Bradbury, Concept for a Blood-Brain Barrier, 1979; F. Joo, Nature 321, 197-198, 1986) can also produce laminin and, via its regulate the growth of neurites of neurons originating from the central nervous system (CNS). In immunohistochemical investigations, the presence of laminin-like immunoreactivity could be detected in the cytoplasm and on the surface of endothelial cells derived from brain microvessels. Further, the neurite-promoting effect of laminin on CNS neurons was also noted in a co-culture system designed especially for conditioning nerve cell cultures continuously with materials released from the cerebral endothelial cells. It is suggested that the endothelial cells may be involved via their laminin secretion in the regulation of axonal growth and guidance in the CNS. PMID- 2327291 TI - Patterns of transiently expressed acetylcholinesterase activity in cerebral cortex and dorsal thalamus of developing rats with cytotoxin-induced microencephaly. AB - Previous studies have demonstrated that acetylcholinesterase (AChE) activity is expressed transiently by thalamocortical neurons of primary sensory systems in developing rat pups. In the present study, prenatal treatment with methylazoxymethanol acetate (MAM) on embryonic day 15, 16, or 17 resulted in rat pups with cerebral cortices markedly reduced in thickness and areal extent. Histochemical studies demonstrated that AChE staining occurs in fiber-like plexuses in primary visual, auditory, and somatosensory regions of developing cerebral cortex of MAM-treated animals, just as in normal developing rats, but that the transient patterns of AChE are found more superficially than normal and they occur in an abnormal patchy distribution. Neuronal somata in thalamic lateral geniculate, medial geniculate and ventral basal nuclei of MAM-treated animals show transient AChE staining indistinguishable from that seen in normal animals. These data indicate: (1) AChE is expressed transiently by thalamocortical neurons in MAM-treated animals, (2) intensity of the transiently expressed AChE is not affected by MAM-induced loss of cortical neurons, and (3) the abnormal AChE patterns in cortex likely reflect the abnormal distributions of thalamocortical terminal fields that are characteristic of MAM-treated animals. PMID- 2327292 TI - Cloning and expression of rfe gene. PMID- 2327293 TI - The activation of C3H/HeJ cells by certain types of lipopolysaccharides. PMID- 2327294 TI - Lipopolysaccharides of non-cholera vibrios possessing common antigen factor to 01 Vibrio cholerae. PMID- 2327295 TI - Modulation of interleukin 1 production by endotoxin, pertussis toxin, and indomethacin. PMID- 2327296 TI - Comparative study of lipopolysaccharide-, lipid IVa-, and lipid X-induced tumor necrosis factor production in murine macrophage-like cell lines. PMID- 2327297 TI - Effects of lipopolysaccharide or recombinant human-interleukin-1 beta on chemiluminescence by peritoneal macrophages from normal and MRL-lpr/lpr mice. PMID- 2327298 TI - Involvement of I-A-restricted B-B cell interaction in the polyclonal B cell differentiation induced by lipopolysaccharide. AB - The present study has examined a functional role of Ia molecules expressed on murine B cells in polyclonal B cell differentiation induced by lipopolysaccharide (LPS). Reverse, IgM PFC responses of unprimed B cells induced by LPS in the apparent absence of T cells and adherent accessory cells were markedly inhibited in a haplotype-specific manner by Fab monomer fragment of anti-class II (Ia) but not anti-class I MHC monoclonal antibody (mAb). However, the degree of inhibition of LPS responses of H-2-heterozygous F1 B cells expressing both parental I-A products by either one of anti-I-A mAb was at best half that of the parental B cells. Interestingly, when (B10 x B10.-BR)F1 (H-2b/k) B cells were fractionated into adherent and nonadherent populations by their ability to bind to parental B10 B cell monolayers, LPS responses of F1 B cells adherent to and nonadherent to the B10 B cell monolayers were selectively inhibited by anti-I-Ab and anti-I-Ak mAb, respectively. These results suggest that LPS-responsive F1 B cells comprise at least two separate populations with restriction specificity for only one of the parental I-A products expressed on B cells. In addition, it was demonstrated that the I-A-restriction specificity of LPS-responsive B cells is "plastic" and determined by H-2-genotype of bone marrow cells present during B cell ontogeny but not by that of radiation-resistant host elements. Namely, the LPS responses of B10-derived B cells from (B10 + B10.BR) (H-2b x H - 2k)F1 radiation bone marrow chimeras but not from B10 (H-2b x H-2k)F1 chimeras became sensitive to the inhibition of anti-I-Ak mAb in the presence of mitomycin C-treated I-Ak-positive B cells, supporting a notion of receptor-Ia molecules interactions rather than like-like interactions. Thus, the present results provide evidence indicating that B-B cell interaction via recognition of self-I-A products is a crucial event in the polyclonal B cell differentiation induced by LPS. PMID- 2327300 TI - The mechanism of adjuvant action of bacterial lipopolysaccharide (LPS) in subcutaneous immunization. PMID- 2327299 TI - Endotoxin and Kupffer cells in liver disease. PMID- 2327301 TI - Lipid A, the immunostimulatory principle of lipopolysaccharides? AB - Lipid A has been found to be an inducer of IL-1 with similar potency as LPS. Partial structures of lipid A or core oligosaccharides are less active or not active at all. We propose that lipid A is the structure responsible for induction of immunostimulatory or immunoregulatory properties of LPS. PMID- 2327302 TI - Anti-LPS region antibody responses and cellular immune responsiveness in typhoid patients. PMID- 2327303 TI - Lipopolysaccharide, but not lethal infection, releases tumor necrosis factor in mice. PMID- 2327304 TI - Biological properties of lipopolysaccharides isolated from Bordetella. AB - Biological activity of lipopolysaccharides (LPSs) separated from Bordetella, i.e., B. pertussis (Bp), B. parapertussis (Bpp) and B. bronchiseptica (Bbs), was determined and compared with that of an Escherichia coli LPS as a control. Two Bp LPS preparations showed marked biological activities comparable to those of E. coli LPS in terms of lethal toxicity in galactosamine-sensitized mice, pyrogenicity in rabbits, mitogenicity in C3H/He spleen cell cultures, macrophage activation and tumor necrosis factor-inducing activity. All the activities except mitogenicity of two Bpp-LPS preparations were lower than or comparable to those of E. coli LPS. Activities stronger than or comparable to those of E. coli LPS were observed in two Bbs-LPS preparations. Among six LPS preparations from Bordetella tested, a Bbs-LPS from L3 strain exhibited the most intensive activities. PMID- 2327305 TI - Septic shock in the elderly. PMID- 2327306 TI - Endotoxin-induced cytokines in human septicemia. PMID- 2327307 TI - Monoclonal antibody to lipid A prevents the development of haemodynamic disorders in endotoxemia. PMID- 2327308 TI - Chronic inflammatory diseases: current therapy and future perspectives. 11th European Workshop on Inflammation. Copenhagen, Denmark, May 18-19, 1989. Proceedings. PMID- 2327309 TI - Effects of cyclosporin and chloroquine on the mitogen-driven cell proliferation and Ig production of human mononuclear cells. PMID- 2327310 TI - Inhibition of monokine release by IX 207-887. PMID- 2327311 TI - Macrophage function during the development of adjuvant disease. AB - Using rat peritoneal macrophages and blood monocytes we examined the relationship of developing adjuvant disease (AD) with the expression of class I and II antigens, release of interleukin-1 (IL-1) and production of prostaglandin E2 (PGE2). We observed that class I and II antigens initially decreased; class II remained low throughout, whereas class I returned to normal. PGE2 and IL-1 gradually increased. Treatment in vivo with the NSAID Na-diclofenac lowered PGE2 and IL-1 release and partly reversed the observed reduction of class I and II antigens. Also, exposure of the cells in vitro to lipopolysaccharide increased class I antigen expression. PMID- 2327312 TI - Humoral autoimmunity to cartilage in rheumatoid arthritis? PMID- 2327313 TI - Increased interleukin 1 beta production of macrophages by proteoglycan fragments deriving from articular cartilage in vitro. PMID- 2327314 TI - Plasma and total blood cell copper in rheumatoid arthritis. PMID- 2327315 TI - Topical anti-inflammatory activity of the glucocorticoid budesonide on airway mucosa. Evidence for a "hit and run" type of activity. PMID- 2327316 TI - Increased in vitro release of interleukin-1 by LPS stimulated peritoneal macrophages obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) during an infectious peritonitis. PMID- 2327317 TI - Lipoxins increase granuloma formation induced by potassium permanganate in vivo. PMID- 2327318 TI - The anti-inflammatory effects of D-myo-inositol-1.2.6-trisphosphate (PP56) on animal models of inflammation. PMID- 2327319 TI - Monoclonal antibodies and arthritis. AB - Monoclonal antibodies to certain cell surface constituents on lymphocytes, monocytes and macrophages have been administered to Lewis rats with developing, established or adoptively transferred arthritis, to determine any immunomodulatory properties. Anti-CD4 antibodies against helper T-lymphocytes produced a dose related inhibition of developing arthritis; high dose levels completely suppressed all symptoms of arthritis and these rats were resistant to further attempts to induce arthritis. Anti-Ia (MHCII) antibodies also inhibited arthritis in a dose related manner; anti-pan T antibodies delayed the onset of arthritis, but antibodies against CD8 and IL-2 receptor positive cells were without effect. Development of type II collagen-induced arthritis was also inhibited by anti-CD4 treatment. Established arthritis could be temporarily inhibited by anti-CD4 antibodies, but rebound of arthritis invariably occurred after stopping treatment, as is the case with cyclosporin A. Similar results with anti-CD4 antibodies were obtained during treatment of arthritis adoptively transferred by arthritogenic T-lymphocytes. From these experiments it is clear that CD4 positive T-lymphocytes have a major role in the induction of adjuvant arthritis and that interaction between CD4 and Ia bearing cells is important. The rebound of arthritis that occurred after withdrawal of anti-CD4 treatment during established disease infers that cells in addition to helper T-lymphocytes are involved in the chronicity of arthritis, but these remain to be elucidated. These findings are discussed in relation to results with monoclonal antibodies in other models of arthritis and human rheumatoid arthritis; the prospects for human therapy are also discussed. PMID- 2327320 TI - Phenotype analysis of "inflammatory" macrophages in rheumatoid arthritis by two colour cytofluorometry and immunohistology. PMID- 2327321 TI - Allergic arthritis induced by cationic proteins. PMID- 2327322 TI - In pursuit of the moment. AB - When one paper is a sequel to a previous one, it is altogether too simple to bore the reader with redundancies. It is also quite too easy to lose track of time and jump from one paper to the next and this almost certainly will happen in the present one. Portions of the earlier writing are initially presented and one would hope that these present a valid reason to continue pursuit of "The Moment." After some discussion, it is felt that various previously unmentioned facets of "The Moment" are discussed and perhaps clarified. But it is not defined. It may defy definition and we could hope that this might intensify our pursuit, since physicians are a stubborn group. PMID- 2327323 TI - Computer simulation in the design of local exhaust hoods for shielded metal arc welding. AB - Computer simulations were used to examine competing exhaust hood configurations for shielded metal arc welding. The welder's breathing zone concentration appears to be an inverse linear function of the computer-predicted hood capture efficiency. Hood aspect ratio, hood flow, and the welder's position relative to the hood all have a significant effect on the breathing zone concentration. The height of the hood above the welding surface showed no significant effect in reducing breathing zone concentration. Further examination of breathing zone concentration as a function of capture efficiency is needed before reliable design methods can be developed using this parameter. PMID- 2327324 TI - Chemical distribution in high-solids paint overspray aerosols. AB - The chemical composition of high-solids basecoat paint overspray aerosols was determined as a function of particle size. Detailed information on the chemical composition of the overspray aerosols is important in health hazard evaluation since the composition and distribution within the airborne particles may differ significantly from the bulk paint material. This study was conducted in a typical down-draft paint booth equipped with air-atomized spray painting equipment. A fixed paint target was used to simulate typical overspray generation conditions and the aerosols were collected isokinetically with a seven-stage cascade impactor for size-fractionated analysis. The overspray aerosol from six paints consisted of organic paint binders with varying amounts of inorganic species as pigments or luster enhancers. These overspray aerosols had mass median aerodynamic diameters (MMAD) ranging from 2.9 to 9.7 microns. The size fractionated paint samples collected on the impaction stages were analyzed by energy dispersive X-ray spectrometry on a scanning electron microscope (SEM EDXRS) to identify the metallic elements. Atomic absorption spectrometry was used to determine the mass distribution of aluminum and iron as indicators of nonuniform distribution. Three of the aerosols containing aluminum were found to have bimodal distributions with most aluminum distributions having cumulative MMADs larger than the total aerosol. Iron in the aerosols was bimodal for three of the paints with all samples having an overall iron MMAD less than or equal to the overspray aerosol MMAD. Analysis using ultraviolet spectrometry revealed that the organic compounds present in the size-fractionated particulate samples consisted of a single, polydispersed mode with an MMAD similar to that of the total overspray aerosol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327325 TI - Comparison of three sampling and analytical methods for measuring m-xylene in expired air of exposed humans. AB - Three breath sampling and analytical methods were tested following exposure of 12 subjects for 4 hr to 75 ppm m-xylene in a controlled environmental chamber. Mixed expired breath was sampled for m-xylene from all 12 subjects with a new stainless steel device that permits continuous mainstream or sidestream sampling of the solvents present. The m-xylene was sampled from the mainstream using charcoal cloth and from the sidestream using Tenax TA. Alveolar breath also was sampled for m-xylene from 6 of these subjects using bags. The carbon dioxide concentrations of the mixed and alveolar samples, obtained from these 6 subjects, were also determined and used to assess the accuracy of the mixed-expired sampling and analytical procedures. Breath sampling was conducted over the immediate 240-min postexposure period. All m-xylene samples were analyzed using gas chromatography with flame ionization detection. Carbon dioxide concentrations were determined with an infrared analyzer. Nonlinear regression analysis was used to model the desaturation of m-xylene via the breath. Overall, the desaturation of m-xylene from all subjects by all methods was best described using three compartment pharmacokinetic models. The precision of each sampling and analytical method, estimated from the residual variabilities of the desaturation curves were 0.13 for alveolar sampling, 0.14 for mainstream-mixed sampling (12 subjects), and 0.23 for sidestream-mixed sampling (12 subjects). For all 12 subjects, the breath m-xylene concentrations determined by sidestream-mixed sampling averaged 83% of those determined by mainstream-mixed sampling; this bias was significant. For the 6 subjects from whom both mixed-expired and alveolar breath samples were obtained, the average m-xylene desaturation rates determined by both mainstream mixed and alveolar sampling were comparable but substantially different from those determined by sidestream-mixed sampling. For these subjects, comparison of the average and individual mixed to alveolar ratios of m-xylene and carbon dioxide showed that mainstream-mixed sampling was accurate and that sidestream mixed sampling was not. PMID- 2327326 TI - Design of Stairmand-type sampling cyclones. AB - An empirical, nondimensional correlation of cut-point Stokes number (Stk0.5) and flow Reynolds number (Re) has been established for small Stairmand-type sampling cyclones. Four cyclones with body diameters of 38, 57, 89, and 140 mm were constructed and tested with monodisperse aerosols over a range of flow rates. The flow rates were chosen to provide preselected increments of particle Froude numbers. These flow rates for the four cyclones spanned the range of 9.4 to 1080 L/min and provided Froude numbers of 1.5, 2.0, 2.5, and 6.0. The resulting Reynolds numbers (based upon cyclone body diameter and inlet flow rate) covered the range of 2.1 x 10(3) to 6.4 x 10(4). Sizes of monodisperse aerosols used in this study were from 3.0- to 17.4-microns aerodynamic diameter. The graphical correlation between cut-point Stokes number and Reynolds number showed there to be no effect of Froude number (for the range of Froude numbers tested). The data have been fit by a least squares procedure to a quadratic logarithmic function. In addition to development of the empirical correlation, the results of this study also provide data pertinent to the regional deposition of liquid particles within the cyclone and to the transmission of solid particles through the cyclone. The carryover of solid, 19-microns diameter particles is only 0.5% greater than that of liquid particles of the same size. PMID- 2327327 TI - Sampling and interpretation errors in aerosol monitoring. AB - The aerosol recorded by simple filter collection or by sophisticated instrument aerosol monitoring may differ considerably from the original, unsampled aerosol. Through use of particle-sizing instruments and computer modeling, the potential biases in sampling, display, and interpretation are demonstrated. The aerosol size distribution and, therefore, the reported number or mass concentration may be affected by the characteristics of the sampling inlet, the transport to the sensor and the sensor itself. The particle count in specific size ranges determines the precision of the registered particle-size distribution, depending on the weighting chosen. The type of display, by histograms or cumulative plot, focuses on different aspects of the size distribution, and the calibration of the aerosol monitor may modify it further. Particle-size classification to simulate a specific region of the human respiratory system may be achieved through inertial classification or the sensitivity characteristics of the aerosol sensor. Aerosol monitors using passive sampling register the same aerosol-size distribution as active ones, if the aerosol is transported to the sensor with the same efficiency as in the active mode. The sources of various types of errors are presented using computer simulations of typical aerosol-size distributions, often combined with measurements found in the literature. Presentation of these errors in graphical format allows the health professional to estimate more accurately the health implications of aerosol measurements. PMID- 2327328 TI - Sensitivity analysis applied to Coburn-Forster-Kane models of carboxyhemoglobin formation. AB - When mathematical model predictions disagree with the behavior of the physiological system modeled, blame is generally placed on the inadequacy of the model. It was shown using the Coburn-Forster-Kane (CFK) models of carboxyhemoglobin (COHb) formation as illustrations, that a sensitivity analysis of the model can provide estimates of the effects of data variability and inaccuracy on model predictions. Sensitivity functions were derived for each variable in the model, and families of them were plotted as functions of time with work level as a parameter. The sensitivity plots identify the variables which can contribute the most to disparities between model and system behavior and illustrate how the relative importance of the error in each variable changes with both time and work level. For example, with exposure to a constant concentration of carbon monoxide (CO) at a constant level of exercise, errors in blood volume determination, initial [COHb], and total hemoglobin concentration do not affect the calculated equilibrium value of blood [COHb]; neither inspired concentration of carbon monoxide nor endogenous production rate affect the rate at which equilibrium is achieved; and all other variables affect both the equilibrium value of blood [COHb] and the rate at which it is achieved. The sensitivity analysis provides a link between model output variability and input or data variability which can be used to assess the value of efforts to reduce data error and to estimate the overall uncertainty of model predictions. PMID- 2327329 TI - Physical characteristics of vibration in relation to vibration-induced white finger. AB - Predicted and observed prevalences and latency periods of vibration-induced white finger (VWF) were examined among workers exposed to hand-arm vibration. The different physical characteristics of vibration--spectra and impulsiveness--were measured. The following groups of workers were included in the study: forest workers (n = 199), pedestal grinders (n = 12), stone workers (n = 16), shipyard workers (n = 171), and platers (n = 5). The exposure to vibration was measured according to the ISO 5349 method. The impulsiveness of vibration was defined as the difference between peak levels and RMS levels. A good agreement was observed between the predicted and observed data for prevalence and latency of VWF in the forest workers. For the tools with high impulsiveness used in grinding, stone works, and shipyard assembly hall, the results were nonconfirmative; and there was a poor correlation between vibration and VWF. The ISO 5349 standard does not consider the high peak values of the vibration signal which may comprise high frequency components and cause short transients in the underlying tissue of the worker's hand. These characteristics in vibration may be hazardous in the genesis of VWF and cannot be predicted when measuring vibration by the present standard method. PMID- 2327330 TI - Effects of humidity and contaminant concentration on respirator cartridge breakthrough. AB - A model described previously was developed further to examine the effect of both test humidity and contaminant assault concentration on respirator cartridge service life. The model emphasized the characterization of cartridge performance in the range of 0% to 50% breakthrough. This study specifically addressed a contaminant concentration range of 250-2000 ppm and test humidities ranging from 0% to 80%. The preconditioning humidity was fixed at 50%. The compounds studied were benzene and methyl chloroform. Two parameters, k' and tau, were described and values of these parameters were determined for each of several different sets of experimental conditions. The determined values of k' and tau were applied using derived expressions to generate each of several complete breakthrough curves for benzene and for methyl chloroform at specified contaminant assault concentrations and test humidities. The effect of humidity on the value of an additional theoretical parameter, a, was investigated. Values of this parameter and the parameters, k and K", were determined for specific test conditions. These values were substituted into pertinent expressions to produce a complete set of breakthrough curves (each curve corresponding to a particular contaminant assault concentration) for a given compound at a fixed test humidity. Several examples of breakthrough curves were generated for methyl chloroform. The results derived from the study agreed with corresponding experimental data. PMID- 2327331 TI - Factors affecting the Heubach and MRI dustiness tests. AB - The effect of test parameters upon material dustiness measured by the Heubach dust measurement appliance and the MRI dustiness tester was studied. The users of these tests can alter test parameters such as flow rate, sampling time, mass of material tested, bulk density, and vibrator setting. The effect of these parameters upon the aerosol produced in the dustiness tester was experimentally studied. All of the parameters affected in a complicated manner, the amount of dust and the size distribution of the dust generated during these tests. Therefore, dustiness test results should not be adjusted for variations in test parameters. The users of dustiness tests need to carefully control dustiness test parameters in order to have reproducible dustiness tests. PMID- 2327332 TI - The application of dustiness tests to the prediction of worker dust exposure. AB - Laboratory bench tests, known as dustiness tests, have been used to evaluate and compare the potential of various powders to cause occupational dust exposure. Dustiness tests are used to develop products with reduced dust emissions. The correlation between dustiness test results and dust exposures was evaluated at two bag dumping and bag filling operations. At one bag dumping and one bag filling operation, there was evidence of a relationship between dustiness test results and dust exposures. In one case, regression analysis showed that dust exposures could be predicted to within nearly one order of magnitude. The variability in this prediction was caused by the inherent variability in the occupational dust exposures. In the other case, there was evidence of a correlation after the data had been adjusted for the effect of varying drop height. At the remaining two operations, no correlation between dust exposures and dustiness test results were observed. These results indicate that the relevance of dustiness tests to occupational dust exposure needs to be evaluated at each site. Because a better option does not exist, manufacturers should continue to use empirical dustiness tests to develop better products in the laboratory. The conclusions reached in the laboratory need to be validated by dust exposure measurements in the field, however. PMID- 2327333 TI - Fire fighters' exposure to carbon monoxide during Australian bushfires. AB - Fatal entrapments of Australian bushfire fighters have led to suggestions that carbon monoxide (CO) poisoning could have contributed to these accidents by impairing the fire fighters' judgement. Carboxyhemoglobin saturation (COHb%) levels were assessed from alveolar CO levels in 24 fire fighters working with handtools and in 12 accompanying scientific observers, before and after fire fighting (duration 37-187 min) on 15 experimental bushfires. Carboxyhemoglobin levels increased on average by 0.7% per hour in the fire fighters and by 0.3% per hour in the observers. Nonsmoking fire fighters had lower COHb% after fires than the smokers had before fires. Estimates of environmental CO concentrations (including cigarette smoke) during the fires averaged 31 parts per million (ppm) for the smokers, 17 ppm for the nonsmoking crew members, and 11 ppm for the observers, none of whom smoked. The highest estimates of environmental CO arising solely from bushfire smoke were 40 to 50 ppm. Smokers were exposed to as much CO from their cigarettes as from bushfire smoke. Carboxyhemoglobin levels at the end of 8-hr fire fighting shifts, predicted from these levels of environmental CO, averaged about 5% (maximum 11%) in smokers and about 3% (maximum 7%) in nonsmokers. Acute levels of COHb% of this degree are not considered to have significant effects on health or performance. These results indicate that bushfire fighters are generally unlikely to experience hazardous levels of CO exposure. PMID- 2327334 TI - Effect of depressed left ventricular function on hemodynamics of normal St. Jude Medical prosthesis in the aortic valve position. AB - To evaluate the effect of left ventricular (LV) dysfunction on Doppler-derived transprosthetic hemodynamic indexes in patients with normally functioning St. Jude aortic valve prostheses, 74 consecutive patients were studied. LV ejection fraction was assessed by using Simpson's biplane rule. The 34 patients with normal ejection fraction (greater than or equal to 0.51) (group A) generally had the highest values of peak (31 +/- 13 mm Hg) and mean (16 +/- 6 mm Hg) gradients, whereas 19 patients with moderate to severe reduction of ejection fraction (less than or equal to 0.31) (group C) had the lowest values (17 +/- 6 and 9 +/- 3 mm Hg, respectively) (p less than 0.05). Significant decreases (p less than 0.05) for acceleration and corrected (for heart rate) velocity time integral in group C were noted compared to group A, and group B (21 patients with mild to moderately reduced ejection fraction [0.50 to 0.32]). A significant inverse correlation for Doppler-derived peak and mean gradients and corrected velocity time integral was demonstrated with increasing aortic valve prosthetic sizes from 19 to 29 mm in group A patients (r = -0.41 to -0.71) but less so in group B or C. Thus, in addition to valve size, LV function should be considered an important factor in detecting prosthetic valvular flow characteristics and dysfunction. A normal derived velocity and gradient in patients with moderately to severely depressed LV function may not rule out significant valvular stenosis. PMID- 2327335 TI - Training effects of long versus short bouts of exercise in healthy subjects. AB - To evaluate the "threshold" duration of exercise required to produce training effects, 18 healthy men aged 51 +/- 6 years completing 30 minutes of exercise training/day were compared with 18 men aged 52 +/- 6 years completing three 10 minute bouts of exercise/day, each separated by at least 4 hours. Exercise training intensity was moderate (65 to 75% of peak treadmill heart rate). During the 8-week study period VO2 max increased significantly in both groups from 33.3 +/- 3.2 to 37.9 +/- 3.5 ml/kg/min in men performing long exercise bouts and from 32.1 +/- 4.6 to 34.5 +/- 4.5 ml/kg/min in men performing short exercise bouts (p less than 0.05 within and between groups). Adherence to unsupervised exercise training performed at home and at work by men in long and short bouts was high; total duration of training completed was 96 and 93% of the prescribed amount and total number of sessions completed was 92 and 93% of that prescribed, respectively. In both groups exercise heart rate measured by a portable microprocessor was within or above the prescribed range for greater than 85% of the prescribed duration. Thus, multiple short bouts of moderate-intensity exercise training significantly increase peak oxygen uptake. For many individuals short bouts of exercise training may fit better into a busy schedule than a single long bout. PMID- 2327336 TI - The sleep electrocardiogram at extreme altitudes (Operation Everest II) AB - To evaluate the effect of sleep at extreme altitudes upon heart rate and rhythm, continuous sleep monitoring was performed in 8 normal young men during a 40-day simulated ascent of Mt. Everest in a hypobaric chamber. Recordings were made for 1 hour before sleep, during sleep and for 1 hour after awakening in all subjects at 760 torr (sea level), in 7 subjects at 390 torr (5,490 m), in 6 at 347 torr (6,100 m) and in 4 at 282 torr (7,620 m). The following results were obtained: periods of sinus bradycardia occurred during sleep in all subjects at 3 altitudes with a mean heart rate of 41 +/- 0.5 beats/min compared to a rate of 44 +/- 2 beats/min at sea level; cycling of the heart rate, presumably due to periodic breathing, occurred in 14 of 17 studies at altitude but not at sea level (cycles consisted of bradycardia [40 beats/min] for 13 seconds and tachycardia [120 beats/min for 5 seconds]; and arrhythmias were observed in all subjects during sleep and consisted of transient bradycardia (heart rates as low as 20 beats/min), sinus pauses frequently associated with escape rhythms and occasional blocked P waves. No arrhythmias were observed at sea level. Simultaneous records of respiration and the electrocardiogram at 12,500 feet (3,810 m) in 5 other normal subjects revealed tachycardia occurring during hyperpnea and bradycardia occurring during apnea. Data indicate that during sleep in normal young subjects at high altitude, cycling of the heart rate with periodic breathing is common, as are bradyarrhythmias. The mechanism of these arrhythmias has yet to be defined. PMID- 2327337 TI - Angiographic assessment of left ventricular volume, afterload and contractile state in normal children. AB - Left ventricular (LV) volume, mass and end-systolic stress were determined angiographically in 20 normal children aged 3 months to 16 years. LV contractile state was assessed by the analysis of the relation between end-systolic stress and ejection phase index or end-systolic volume. The LV volume and mass closely correlated with the body surface area. The LV mass/end-diastolic volume ratio (0.94 +/- 0.13 g/ml), ejection fraction (0.67 +/- 0.03) and circumferential end systolic stress (163 +/- 21 kdynes/cm2, 165 +/- 21 g/cm2) remained constant despite the extensive increase in LV volume with physical growth. In all subjects significant inverse correlations were observed between end-systolic stress and ejection fraction or mean normalized systolic ejection rate. The ratio of the circumferential end-systolic stress to end-systolic volume index ranged from 5.00 to 12.57 (7.49 +/- 1.88). The ratio inversely correlated with age (r = -0.74, p less than 0.001), indicating that this ratio for estimating LV contractility is associated with ventricular size. These results suggested that the LV mass increased adequately in response to the extensive increase in LV cavity volume to maintain the end-systolic stress during growth in childhood and that physiologic cardiac growth was associated with appropriate hypertrophy with no significant change in LV contractile state. PMID- 2327338 TI - Effects of sample volume location, imaging view, heart rate and age on tricuspid velocimetry in normal subjects. AB - The effects of imaging view and sample volume location on tricuspid velocimetry and of heart rate and aging on mitral and tricuspid inflow were evaluated in 41 normal subjects aged 20 to 76 years. Pulsed Doppler recordings were obtained in the parasternal short-axis, right ventricular inflow and apical 4-chamber views at the level of the tricuspid and mitral anuli and 1 cm caudad and 1 cm cephalad to the tricuspid anulus in the 4-chamber apical view. The right ventricular filling pattern was not affected by imaging view. However, placement of the sample volume 1 cm cephalad resulted in a 16% reduction (p less than 0.01) in early velocity with a 9% increase in atrial filling fraction. Conversely, late velocity was 11% higher (p less than 0.05) at the anular level versus the other locations. Right and left ventricular filling velocities were modestly related (r = 0.50 to 0.63). Relations between age and tricuspid late velocity, velocity ratio and atrial filling fraction were weaker (r = 0.34 to 0.47; all p less than 0.05) than those between age and mitral variables (r = 0.59 to 0.74. Also, aging had a greater effect on mitral than tricuspid late velocity (i.e., a steeper slope; p less than 0.01). Tricuspid late velocity and atrial filling fraction were each modestly inversely related to RR interval (r = -0.48, r = -0.54; p less than 0.01). Thus, tricuspid velocity is affected by sample volume location, aging and heart rate, but not imaging view. Sample volume location, heart rate and age should be considered when evaluating right ventricular inflow parameters. PMID- 2327339 TI - Comparison of echocardiographic quantitation of left ventricular ejection fraction to radionuclide angiography in patients with regional wall motion abnormalities. PMID- 2327340 TI - Rupture of the left ventricular free wall during acute myocardial infarction without hemopericardium. PMID- 2327341 TI - Usefulness of right-sided cardiac catheterization during "routine" coronary angiography. PMID- 2327342 TI - Electrophysiologic effects of oral theophylline in sinus bradycardia. PMID- 2327343 TI - Different cardiodepressant potency of various calcium antagonists in human myocardium. PMID- 2327344 TI - Development of cholesterol embolization syndrome after intravenous streptokinase for acute myocardial infarction. PMID- 2327345 TI - Left internal mammary artery occlusion after mastectomy and radiotherapy. PMID- 2327347 TI - Stepwise transgression. PMID- 2327346 TI - Doppler measurement of posterior left ventricular wall velocity. PMID- 2327348 TI - Comparison of standard 12-lead and modified exercise electrocardiograms. PMID- 2327349 TI - Panic disorder and depression in patients with chest pain not due to coronary artery disease. PMID- 2327350 TI - Percutaneous balloon mitral valvotomy: single versus double balloon techniques. PMID- 2327351 TI - Scanning electron microscopy of floppy mitral valve. PMID- 2327352 TI - Left ventricular-to-right atrial shunt in perimembranous trabecular ventricular septal defect with aneurysmal transformation. PMID- 2327353 TI - Doppler method of assessing ventricular ejection force. PMID- 2327354 TI - Right ventricular ischemia diagnosed by ST-segment elevation in precordial leads. PMID- 2327355 TI - Two-dimensional echocardiography and Doppler findings in cerebral arteriovenous malformations. PMID- 2327356 TI - Mechanisms of stress-induced ST elevation and negative T-wave normalization studied by serial cardiokymogram in patients with a previous myocardial infarction. AB - Seventeen patients with a previous myocardial infarction were studied during pacing to characterize the clinical correlates of ST elevation, to analyze the relation between ST elevation and negative T-wave normalization and to investigate the mechanism of these electrocardiographic changes. Myocardial ischemia was evaluated by measurement of blood lactate, and wall motion was analyzed using cardiokymographs concurrently and serially. Results show that ST elevation and negative T-wave normalization were most marked in leads containing abnormal Q waves, that ST elevation greater than or equal to 1 mm during pacing was associated with a significant increase in left ventricular end-diastolic pressure and deterioration of left ventricular wall motion and that the magnitude of ST elevation and negative T-wave normalization was significantly correlated, but the latter appeared earlier and more markedly. In addition, there was no significant correlation between the extent of either ST elevation or negative T wave normalization and myocardial lactate production. Thus, ST elevation and negative T-wave normalization are caused by abnormal left ventricular wall motion rather than myocardial ischemia. Negative T-wave normalization is a more sensitive marker of abnormal wall motion than ST elevation in patients with a previous myocardial infarction. PMID- 2327357 TI - Heparin and infarct coronary artery patency after streptokinase in acute myocardial infarction. AB - Anticoagulant therapy is frequently used after thrombolytic agents in the treatment of acute myocardial infarction (AMI) although it is unclear that such therapy will prevent subsequent infarct vessel reocclusion. The role of duration of heparin therapy in maintaining infarct artery patency was studied retrospectively in 53 consecutive AMI patients who received streptokinase therapy and underwent coronary angiography acutely and at 14 +/- 1 days. Of the 39 patients with initial infarct vessel patency, patency at follow-up angiography was observed in 100% (22 of 22) of those who received greater than or equal to 4 days of intravenous heparin but in only 59% (10 of 17) of those patients who received less than 4 days of heparin (p less than 0.05). Of the 14 patients not initially recanalized after streptokinase, patent infarct-related arteries at follow-up angiography were found in 3 of 8 (38%) treated with greater than or equal to 4 days of heparin therapy but in none of the 6 patients treated for less than 4 days (difference not significant). No significant difference in hemorrhagic complications was noted between the short- and long-term heparin treatment groups. Thus, greater than or equal to 4 days of intravenous heparin therapy after successful streptokinase therapy in AMI is more effective in maintaining short-term infarct vessel patency than a shorter duration of therapy and it may maintain the short-term patency of the infarct vessel in those patients who later spontaneously recanalize. PMID- 2327358 TI - Diagnostic features of body surface potential maps in patients with myocardial ischemia and normal resting 12-lead electrocardiograms. AB - Body surface maps recorded from 35 ischemic patients with normal resting 12-lead electrocardiograms were compared with those obtained from 36 age- and sex-matched normal subjects. From instantaneous maps of each subject 187 variables were derived relating to the configuration (80 variables) and magnitude (104 variables) of the potential distribution and duration of the electrocardiographic intervals (3 variables). By using stepwise discriminant analysis we selected 3 variables whose linear combination enabled us to correctly allocate 91% of the study population (jacknife procedure; specificity 92%, sensitivity 91%). To substantiate the validity of the results the discriminant function was tested on a new independent population consisting of 27 ischemic patients and 54 normal subjects from another laboratory. A proper allocation was obtained in 86% of the cases (specificity 87%, sensitivity 85%). The large number of correctly classified ischemic patients and the repeatability of the results indicate that the adopted criteria are good markers of ischemic heart disease. PMID- 2327359 TI - Risk factors for progression of atherosclerosis six months after balloon angioplasty of coronary stenosis. AB - To assess the possible progression of coronary artery disease after percutaneous transluminal coronary angioplasty (PTCA) and its relation to risk factors and restenosis, 124 patients who underwent a first successful PTCA were studied. All had routine follow-up angiography 5 to 8 months after PTCA. Restenosis was defined as a 30% decrease in diameter stenosis or a return to greater than 50% stenosis, and progression (in any nondilated site) as a 20% decrease in diameter stenosis, assessed by a video-densitometric computer-assisted technique. Univariate and multivariate analysis with respect to progression was carried out for age, sex, initial unstable angina, previous myocardial infarction, diabetes mellitus, hypertension, hypercholesterolemia (greater than or equal to 6.2 mmol), smoking habits, Jenkins' score, dilated artery and restenosis. Forty-one patients (33%) had restenosis, and 23 (19%) had evidence of progression; 20 (87%) of these latter patients had restenosis and 3 (13%) did not. Univariate correlates of progression were: previous myocardial infarction (p less than 0.05), higher Jenkins' score (p less than 0.0003) and restenosis (p less than 0.0001). Restenosis was the only multivariate correlate (p less than 0.00003). Progression at routine angiography after PTCA is not rare, and appears to be related to both the initial extent of coronary artery disease and restenosis. PMID- 2327360 TI - Metabolic and functional effects of perfluorocarbon distal perfusion during coronary angioplasty. AB - Myocardial lactate metabolism and left ventricular function were studied in 12 patients during angioplasty of the left anterior descending artery performed with distal coronary perfusion (oxygenated and nonoxygenated Fluosol) and by conventional technique without distal perfusion. Before balloon inflation there was net lactate extraction by the heart (31 +/- 6%). During balloon inflations performed with distal perfusion there was net lactate release into the great cardiac vein while the balloon was inflated; the great cardiac vein lactate concentration was approximately 25% lower during perfusion with oxygenated versus nonoxygenated Fluosol (p less than 0.02) indicating less myocardial lactate release. After balloon deflation washout of lactate into the great cardiac vein (net myocardial release) was observed in all 3 protocols. Left ventricular ejection fraction measured by echocardiography decreased markedly during nonperfused (53 +/- 3 to 36 +/- 3%, p less than 0.001) and nonoxygenated Fluosol (52 +/- 2 to 30 +/- 3%, p less than 0.001) inflations. This dysfunction was largely prevented by oxygenated Fluosol where only a minimal decrease in ejection fraction (51 +/- 2 vs 48 +/- 2%, p less than 0.02) occurred. Analysis of regional contractile function yielded similar results. Although oxygenated perfluorocarbons decrease cardiac lactate release during angioplasty, this study provides evidence for the onset of lactate production even when ventricular function is preserved. PMID- 2327361 TI - Detection of human collateral circulation by vasodilation-thallium-201 tomography. AB - Coronary arteriolar vasodilation may provoke redistribution of flow to collateral dependent jeopardized myocardium. To assess the physiologic significance of collaterals, 80 consecutive post-infarction patients (age 58 +/- 8 years) underwent vasodilation-redistribution thallium-201 tomographic imaging after administration of 0.56 mg of intravenous dipyridamole/kg body weight. Circumferential profile analysis of thallium-201 uptake and redistribution in representative left ventricular tomograms provided quantitative assessment of transient and fixed defects and separation between periinfarctional and distant inducible hypoperfusion. Tomographic perfusion data were correlated to wall motion and collateral circulation between distinct anatomic perfusion territories. Patients were grouped according to presence (59%) or absence (41%) of angiographically visible collateral channels to jeopardized myocardium. In the presence of collaterals, distant reversible defects were larger than in absence of collaterals (p less than 0.05); the extent of combined periinfarctional and distant redistribution was also larger in collateralized patients (p less than 0.025), whereas the size of the persistent perfusion defect was similar in both groups. By prospective analysis the tomographic perfusion pattern of combined periinfarctional and distant redistribution revealed a sensitivity of 85% and a specificity of 78% for the detection of significant collateral circulation in this group of patients. Thus, using the exhausted flow reserve as a diagnostic tool, vasodilation-thallium-201 tomography has the potential to identify and quantitate collateralized myocardium in post-infarction patients and may guide diagnostic and therapeutic decision-making. PMID- 2327362 TI - Acute changes in pacing threshold and R- or P-wave amplitude during permanent pacemaker implantation. AB - This study examines the changes in pacing threshold and R- or P-wave amplitude during the first 30 minutes after implantation of tined and screw-in leads. The leads examined were those of 1 manufacturer (Medtronic) and consisted of 3 ventricular pacing leads (model numbers 6957 unipolar screw-in [11 patients], 6961 unipolar tined [12 patients] and 6962 bipolar tined [7 patients]) and 1 atrial lead (model number 6957J unipolar screw-in [10 patients]). After optimal lead position was obtained fluoroscopically in the right ventricular apex or right atrium, the pacing threshold and R- or P-wave amplitudes were measured at 5 minute intervals for 30 minutes. The acute ventricular pacing threshold with the screw-in lead was significantly higher than with the tined lead (0.84 +/- 0.17 vs 0.58 +/- 0.15 volts; p less than 0.001). There was a significant (p less than 0.001) acute decrease in the ventricular pacing threshold with both lead types, with the maximum decrease occurring 5 minutes after lead implantation. There was a significant acute increase in R-wave size with the ventricular screw-in lead that peaked 20 minutes after lead implantation (11.9 +/- 3.0 to 14.7 +/- 4.1 mV; p less than 0.001). The atrial screw-in lead behaved in a manner identical to its counterpart in the ventricle. In conclusion, there are acute changes in the pacing threshold and R- or P-wave amplitude obtained with tined and screw-in pacing leads.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327363 TI - So-called fibroepithelial polyps of the vagina exhibiting an unusual but uniform antigen profile characterized by expression of desmin and steroid hormone receptors but no muscle-specific actin or macrophage markers. AB - The nature of the atypical, often multinucleated stromal cells proliferating in the so-called fibroepithelial polyps of the vagina (FEPV) is obscure. The authors therefore investigated immunohistochemically four polyps of this type with a panel of monoclonal and polyclonal antibodies, including those directed against intermediate filaments, steroid hormone receptors, and macrophage antigens. The authors found that the atypical stromal cells of FEPV expressed vimentin, desmin, and receptors for estrogen and progesterone but lacked all the other markers studied. The homogenous antigen profile strongly suggests that FEPV form a disease entity whose characteristic cells are special hormone-sensitive stromal cells with a myoid component of differentiation. Morphologically similar stromal cells expressing steroid hormone receptors but lacking desmin were found in myxomatoid subepithelial regions of the vaginal wall and the cervix. PMID- 2327364 TI - Deoxyribonucleic acid ploidy and cell cycle analysis of colorectal carcinoma by flow cytometry. A prospective study of 137 cases using fresh whole cell suspensions. AB - Several retrospective studies suggest that abnormal deoxyribonucleic acid (DNA) content in colorectal carcinoma correlates with adverse clinical outcome. Many of these studies have used naked nuclei retrieved from formalin-fixed, paraffin embedded tissues for flow cytometry. The purpose of this study was to prospectively analyze 137 colorectal carcinomas using fresh whole-cell suspensions for flow cytometry and to determine whether abnormal DNA content (DNA aneuploidy or tumors with high proliferative activity) correlates with Dukes' stage, histologic grade, lymphocytic infiltration of the tumor, tumor fibrosis, extramural venous spread, or tumor size. Cell suspensions for flow cytometry were prepared by enzyme disaggregation with collagenase XI, DNase, and trypsin. Satisfactory DNA histograms were obtained from 132 of the 137 samples. The mean coefficients of variance for the G1/G0 of the external 2C control, internal 2C populations, and aneuploid populations were 2.5, 3.5, and 3.5, respectively. The mean percentage of viable cells was 97%. Of 132 cases, 102 (77%) demonstrated abnormal DNA histograms, of which 77 (58%) showed DNA aneuploidy. Abnormal DNA histograms of DNA aneuploidy did not correlate with Dukes' stage. Tumors of higher histologic grade were more likely to demonstrate DNA aneuploidy, however, these differences did not reach statistical significance. The authors conclude that (1) satisfactory DNA histograms can be obtained with the use of a fresh, whole-cell technique; (2) abnormal DNA histograms did not statistically correlate with standard clinical, grading, or staging parameters; and (3) carcinomas of high histologic grade showed an increased proportion of aneuploid DNA histograms, but this trend did not reach statistical significance. PMID- 2327365 TI - Image analysis confirmation of DNA aneuploidy in flow cytometric DNA distributions having a wide coefficient of variation of the G0/G1 peak. AB - With nuclei extracted from paraffin-embedded tissues, resolution of normal diploid DNA and abnormal near-diploid/aneuploid populations by flow cytometry (FCM) is especially difficult. These samples, compared with fresh tissue, tend to show a broader DNA distribution, appearing as a wide (high) coefficient of variation (CV) of the G0/G1 peak. To address the question of whether there may be aneuploid populations hidden in wide CV diploid G0/G1 peaks, the authors measured DNA content in nuclei extracted from paraffin-embedded tumor tissue by morphometric image analysis (IA) in addition to FCM. Of 29 samples showing little evidence of DNA aneuploidy by FCM, in 20 of 20 with G0/G1 CVs greater than or equal to 5.50% there was an aneuploid population when analysis was performed by IA. Of the remaining nine samples with CVs less than or equal to 4.41%, all were diploid in the G0/G1 region by both FCM and IA. The presence of aneuploid populations in FCM distributions with wide CV G0/G1 peaks can be confirmed by IA. PMID- 2327366 TI - The effect of various cell separation procedures on assays of neutrophil function. A critical appraisal. AB - Neutrophils are considered fragile cells, easily damaged by improper handling. Assays of neutrophil function frequently require preliminary isolation procedures that may be potentially harmful. The authors did an extensive investigation of the effects of currently used isolation procedures on a broad spectrum of functional assays that included: 1) phagocytosis; 2) bacterial killing by a culture technique and tritiated thymidine labeling; 3) candidacidal activity by methylene blue dye exclusion and differential Giemsa staining; 4) quantitative unstimulated and histochemical stimulated nitroblue tetrazolium dye reduction; 5) chemiluminescence; 6) random locomotion; and 7) chemotaxis by the agarose method. In addition, cells were examined morphologically by electron microscopy, and the granule density was quantitated by morphometric analysis. Isolation techniques included erythrocyte sedimentation, hypotonic lysis, gradient density separation using Ficoll-Hypaque, and counterflow centrifugal elutriation. The purest neutrophil suspensions were obtained by density gradient separation and counterflow centrifugal elutriation with mean neutrophil percentages of greater than or equal to 94%. Regardless of the isolation procedure, neutrophils were similar in all groups (P greater than .05) in the following studies: phagocytosis, nitroblue tetrazolium dye reduction, bacterial killing, candidal killing, inhibition of candidal germ tube formation, and cytoplasmic granulation. Differences were noted in assays of neutrophil migration and chemiluminescence. Neutrophil suspensions isolated by counterflow centrifugal elutriation and Ficoll Hypaque had the highest scores for random migration and chemotaxis. These differences can be related to the purity of the neutrophil suspension rather than the harmful effects of the isolation procedures. Erythrocyte contamination affected both the slope and the time to peak response in the chemiluminescence assay. Exposure of neutrophils to cold temperatures (0-4 degrees C) for 1.5 hours impaired both random locomotion and chemotaxis. Current recommendations for the storage, transport, and preparation of leukocytes for neutrophil function studies need to be reassessed. PMID- 2327367 TI - One-stage method for assay of tissue factor activity of leukemic cell with special reference to disseminated intravascular coagulation. AB - Tissue factor activity (TFA) of leukemic cells (1 x 10(8) cells/mL) was measured in 44 patients with acute nonlymphoid leukemia (ANLL) by the one-stage assay using factor-IX deficient plasma (OSA-dIX) and two-stage assay (TSA). According to the preventative heparin dose schedule based on the TFA measured by the TSA, all disseminated intravascular coagulation (DIC) was controlled successfully. The procedure of the TSA was too complicated for clinical use, and its minimal measurable value was 125 units (U)/L of TFA. The OSA-dIX was simpler in its procedure and sensitive enough to measure accurately a TFA quantity as small as 30 U/L with high reproducibility. In 20 ANLL patients with 125 U/L or more of TFA measured by both assays, there was a significant relationship between their logarithms of TFA (r = 0.93, P less than 0.01). These results suggested that DIC complication in ANLL patients would be controlled successfully by the administration of heparin dosage based on the TFA measured by the OSA-dIX. PMID- 2327368 TI - The optimum urine collections for the detection and monitoring of Bence Jones proteinuria. AB - Twenty patients with malignant disease and Bence Jones (BJ) proteins were studied to determine the optimum urine collections for the detection and monitoring of light chain proteinuria. A 24-hour urine protein collection was followed by individual collections of each sequentially voided specimen over the same time interval. Samples were analyzed quantitatively for protein, and protein electrophoresis was performed on each specimen. Only one patient had BJ protein nondetectable by protein electrophoresis in the early morning specimen. Six patients had one or more random specimens (excluding the early morning specimens) absent for BJ protein on protein electrophoresis. Three patients had nondetectable protein on electrophoresis of the 24-hour specimen despite having some random specimens positive. All random specimens with protein values exceeding 0.20 g/L had BJ protein visibly detectable on electrophoresis. Thirteen specimens with protein less than 0.05 g/L still had BJ protein detected by electrophoresis. There was a linear relationship between the early morning protein concentration and the total 24-hour urinary protein production. The authors conclude that early morning specimens or 24-hour urine collections are preferable for the detection and monitoring of light chain proteinuria. These collection methods are not mutually exclusive because there are individual patients who will be negative in one collection but positive in the other. PMID- 2327369 TI - Variability in the fibrinogen and von Willebrand factor content of cryoprecipitate. Implications for reducing donor exposure. AB - Advances in the preparation of commercial Factor VIII concentrates have decreased the clinical use of cryoprecipitate to replace Factor VIII coagulant activity. Cryoprecipitate is now frequently transfused as a source of fibrinogen or von Willebrand factor (vWF). The minimum acceptable content of Factor VIII is prescribed, but no attempt is made to optimize, standardize, or assess the content of fibrinogen or vWF in cryo. If reasonably accurate information on the composition of cryoprecipitate were available, the physician could calculate an appropriate dose of cryo, thus avoiding unnecessary donor exposures and waste of product. This study was designed to measure the functionally active vWF and fibrinogen in cryoprecipitate prepared by three techniques in an attempt to optimize the yield of these hemostatically important components, and to obtain accurate information on the composition of the product. Cryoprecipitate was made from 82 units of fresh frozen plasma (FFP) as follows: (1) most of the supernatant plasma was expressed from "dry" cryo; (2) about 15 mL of plasma was left in each "regular" unit; and (3) "overnight" units were made from FFP thawed overnight in a refrigerator rather than in a 4 degrees C water bath as for the dry and regular units. Dry, regular, and overnight units had volumes of 8.8 +/- 1.5, 16.6 +/- 3.9, and 15.1 +/- 2.4 mL/bag, respectively. Dry cryoprecipitate units had significantly less fibrinogen and vWF than regular or overnight units. The vWF multimer pattern for all three types of cryoprecipitate was indistinguishable from that of normal pooled plasma. Thus, the amount of plasma expressed during preparation has a significant impact on the vWF and fibrinogen content of the resulting product. The amounts of these clinically important proteins should be assayed as a step toward rational determination of optimal cryoprecipitate doses in specific clinical settings. PMID- 2327370 TI - Special report: ASCP Colorado Springs conference. The future content and structure of residency training in pathology. PMID- 2327371 TI - Guidelines for computer-related articles. PMID- 2327372 TI - Potential and problems of the in situ molecular detection of viral genomes. PMID- 2327373 TI - Method already in use. PMID- 2327374 TI - Drop CIN? PMID- 2327375 TI - Controversies, dilemmas, and dialogues. A hyperplastic polyp is discovered on flexible sigmoidoscopy. Is a full colonoscopy indicated? PMID- 2327376 TI - Immunologic abnormalities in alcoholic liver disease. PMID- 2327377 TI - 1989 Henry Baker lecture. Inflammatory bowel disease: back to the future. PMID- 2327378 TI - The effect of raw onions on acid reflux and reflux symptoms. AB - Patients with gastroesophageal reflux often describe heartburn after "spicy meals." One ingredient common to most such meals is onion. We investigated the effects of onion on acid reflux and reflux symptoms in 16 normal subjects and 16 heartburn subjects. Subjects were studied with an esophageal pH probe for 2 h after the ingestion of a plain hamburger and a glass of ice water. The identical meal, with the addition of a slice of onion, was ingested on a counterbalanced day. Variables measured were number of reflux episodes, percentage of the time pH was less than four, heartburn episodes, and belches. Ingestion of onions did not increase any of the reflux variables measured in normals. However, onions significantly increased all measures in heartburn subjects, compared with the no onion condition, and compared with normals under the onion condition. Onions can be a potent and long-lasting refluxogenic agent in heartburn patients. PMID- 2327379 TI - Prospective evaluation of blind brushing of the esophagus for Candida esophagitis in patients with human immunodeficiency virus infection. AB - We prospectively evaluated the diagnostic value of blind brushing of the esophagus via nasogastric tube in 66 patients with human immunodeficiency virus (HIV) infection [acquired immune deficiency syndrome (AIDS) (N = 59), or AIDS related complex (ARC), (N = 7)] complaining of odynophagia and/or dysphagia. Brushings were obtained between 20 and 35 cm from the incisors. Patients then underwent upper endoscopy with directed brushings and biopsies; esophageal lavage was also done in the first 40 patients. Candida esophagitis was defined as an abnormal appearance of the esophageal mucosa, together with microscopic evidence of pseudohyphae in the endoscopic brushings or invasive candidiasis on biopsy. The presence of oral thrush was also recorded. Candida esophagitis was present in 28 (42%) of the 66 patients. Blind brushings diagnosed candidiasis in 27/28 cases and produced five false positives (sensitivity 96%, specificity 87%). Blind brushing of the esophagus was significantly more sensitive than the presence of oral thrush for the diagnosis of esophageal candidiasis (p = 0.02). Oral thrush was found in only 20/28 cases of Candida esophagitis and in eight patients without Candida (sensitivity 71%, specificity 79%). Esophageal lavage yielded Candida in all cases (sensitivity 100%) but had a poor specificity (64%). We conclude that blind brushing of the esophagus is a rapid, safe, and economical way to diagnose Candida esophagitis in patients with AIDS. This procedure can be performed by primary care physicians with minimal loss of sensitivity and specificity as compared to endoscopy. PMID- 2327380 TI - Ablation of exaggerated meal-stimulated gastrin release in duodenal ulcer patients after clearance of Helicobacter (Campylobacter) pylori infection. AB - An exaggerated increase in meal-stimulated gastrin is a common finding in patients with duodenal ulcer. Duodenal ulcer patients also exhibit an increase in the number of parietal cells, which results in an increase in maximum acid output. There are also data to suggest that acid hypersecretion may not predate the ulcer disease, but is acquired, possibly due to the trophic effects of the exaggerated gastrin release on parietal cells. We investigated meal-stimulated gastrin release in nine Helicobacter pylori-infected individuals; eight patients with chronic duodenal ulcer and one H. pylori-infected healthy control, both before and after therapy designed to eradicate H. pylori infection. We also simultaneously measured intragastric pH in six duodenal ulcer patients. Eradication of the H. pylori infection reversed the exaggerated meal-stimulated gastrin release (gastrin secretion fell from 141 + 16 pg/ml/h before treatment to 98 +/- 7 pg/ml/h after, p less than 0.01) without affecting intragastric pH. Whereas exaggerated meal-stimulated gastrin release may be an important pathogenetic feature of duodenal ulcer disease, we conclude that it is secondary to the H. pylori infection. This study provides further insight into the role of H. pylori in the pathogenesis of duodenal ulcer disease. We postulate that reversal of the abnormalities in gastrin secretion will be associated with a gradual return of gastric secretion to normal. PMID- 2327381 TI - 14C-urea breath test for the detection of Helicobacter pylori. AB - The high urease activity of Helicobacter pylori can be used to detect this bacterium by noninvasive breath tests. We have developed a 14C-urea breath test which uses 5 microCi 14C with 50 mg nonradioactive urea. Breath samples are collected at baseline and every 30 min for 2 h. Our study compared the outcome of the breath test to the results of histology and culture of endoscopically obtained gastric biopsies in 84 patients. The breath test discriminated well between the 50 positive patients and the 34 patients negative for Helicobacter pylori: the calculated sensitivity was 100%, specificity 88%, positive predictive value 93%, and negative predictive value 100%. Treatment with bismuth subsalicylate and/or ampicillin resulted in lower counts of exhaled 14CO2 which correlated with histological improvement in gastritis. The 14C-urea breath test is a better "gold standard" for the detection of Helicobacter pylori than histology and/or culture. PMID- 2327382 TI - Gastric juice immunoreactive epidermal growth factor levels in patients with peptic ulcer disease. AB - Immunoreactive epidermal growth factor (IR-EGF) was measured by a highly sensitive and specific radioimmunoassay in gastric juice samples obtained during endoscopy from 26 control subjects, 44 patients with duodenal ulcers, and 18 with benign gastric ulcers. In the active stage, the concentrations of the peptide were consistently reduced, compared with those found in control subjects (592.7 +/- 55.8 pg/ml), in both duodenal (262.6 +/- 21.4 pg/ml) and gastric ulcer patients (320.2 +/- 34.1 pg/ml) (p less than 0.001 and 0.01, respectively). Mean IR-EGF values distinctly lower than in the controls were still present in the gastric juice of patients with inactive duodenal ulcers (349.7 +/- 35.9 pg/ml; p less than 0.001), whereas no difference was observed in patients with healed gastric ulcers (502.2 +/- 132.3 pg/ml). Although these findings suggest a possible role for EGF deficiency in the pathogenesis of peptic ulcer disease, the pathophysiological significance of our results (if any) remains to be elucidated. PMID- 2327383 TI - Overt gastrointestinal bleeding in the course of chronic low-dose aspirin administration for secondary prevention of arterial occlusive disease. AB - We describe 13 patients who developed erosive gastritis with overt gastrointestinal bleeding while receiving 75-250 mg nonbuffered aspirin per day for the secondary prevention of cardiac or cerebrovascular events. The bleeding occurred despite good initial tolerance to aspirin for several months or years. All patients were elderly and had severe atherosclerotic cardiovascular disease. Our data suggest that, contrary to common belief, very low doses of nonbuffered aspirin are attendant with clinically apparent gastrointestinal complications. PMID- 2327384 TI - Macrolipasemia: a rare cause of persistently elevated serum lipase. AB - This report describes a variant form of lipase found in a patient with cryptogenic liver cirrhosis. Serum lipase in this patient showed persistently increased activity with simultaneously normal activity of amylase. Results of exclusion chromatography demonstrate that the lipase activity in the serum of this patient eluted as a macromolecule. Since macromolecular complexes were not fixed by protein A, it seems unlikely that lipase is attached to IgG. Tests of the sera from 20 patients with raised serum lipase activity in acute pancreatitis or an acute episode of chronic pancreatitis revealed, in two patients, that a small but reproducible proportion of the total lipase activity eluted in the region of the macrolipase. In addition, 10% and 18% of the total lipase activity was found in the elution region of the macrolipase in two commercial pooled sera used for quality control. The results show that, in rare cases, macrolipasemia must be considered a possible cause of raised serum lipase activity. PMID- 2327385 TI - Pathologist agreement in the interpretation of colorectal polyps. AB - Practicing physicians commonly perform flexible sigmoidoscopy in their offices. Polyploid lesions are frequently biopsied and sent to community hospitals for pathological interpretation. The pathologist's opinion often determines the course of medical follow-up for the patient, especially in cases in which early malignancy is suspected. This paper addresses the agreement of community-based pathologists regarding the interpretation of colorectal polyp pathology. Ten pathological slide sections were sent to 22 different community-based pathologists in southeast Michigan. These pathologists were asked to record their diagnosis of the specific histologies represented in each of the slides. The results indicated a high level of agreement of histologies in the dichotomous categories of hyperplasia versus adenoma. However, there was considerable disagreement on the presence of moderate or severe atypia. The results of this study indicate that clinicians performing biopsies on patients at risk for colorectal cancer should be aware of the potential for diagnostic variability among pathologists, and should plan follow-up strategies which may include seeking second pathological opinions when a significant patient management decision must be made. PMID- 2327386 TI - Persistent immune deficiency in patients with alcoholic hepatitis. AB - T-lymphocyte subset numbers, recall-antigen skin test responses and mitogen induced lymphocyte proliferation assays were investigated in 12 patients with severe alcoholic hepatitis (AH). Serial studies of these parameters were obtained at intervals of 1 or 2 wk. Patients with AH had lower peripheral blood lymphocyte counts with corresponding decreases in T-cell subset numbers that were persistent in the serial evaluations. T8 cells were disproportionately decreased, with a significant resultant increase in the T4:T8 ratios. Compared with controls, AH patients had significantly smaller cutaneous responses to Candida albicans antigen (p less than 0.05) and mumps antigen (p less than 0.005). Fifty-eight percent of patients were anergic when tested with a battery of four antigens. Patients with AH had increased concanavalin A-, but not phytohemagglutinin induced lymphocyte proliferative responses. These serial analyses confirm previous observations of cell-mediated immune dysfunction in patients with severe AH. Moreover, there is a persistence of these abnormalities for at least 6 wk after withdrawal from alcohol. PMID- 2327387 TI - Liver involvement in Addison's disease. AB - Three patients admitted because of slightly increased serum aminotransferases were found to have Addison's disease. A review of 16 other patients with Addison's disease who had serum aminotransferase activity [aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT)] determined prior to treatment revealed one more patient with slightly increased aminotransferase activity that could not be explained by known causes of increased serum aminotransferase levels. In all four of these patients, the enzymes normalized within 1 wk of corticosteroid substitution treatment. Liver biopsy in one patient revealed discrete lymphocytic infiltrates in the portal zones. On the basis of these observations, we recommend that the possibility of Addison's disease should be considered in patients with obscure slight hypertransaminasemia. PMID- 2327388 TI - Esophageal perforation due to nasogastric intubation. AB - Esophageal perforation is a rare but catastrophic complication of nasogastric intubation. Diagnosis is frequently delayed, resulting in high mortality. We report a case of perforation due to nasogastric intubation in an otherwise normal esophagus. Patients at high risk of this complication can be identified, and special techniques can be used to avoid perforation. Percutaneous endoscopic gastrostomy is an alternative to nasogastric intubation for long-term enteral feeding. When nasogastric intubation is performed, clinical tests of tube position are not sufficient to guarantee proper tube position. The tip of the tube must be visualized radiographically in the stomach prior to initiation of tube feeding. When perforation does occur, proper management is often controversial. Therapy must be tailored to each individual case for the best possible outcome. PMID- 2327389 TI - Symptomatic differentiation of duodenal from gastric fistulas in Crohn's disease. AB - Fistulization to the duodenum or stomach from a diseased segment of bowel in Crohn's disease is rare, with only 63 cases reported. We report an additional two cases of Crohn's disease with recurrent fistulization to the duodenum. Although one or both patients complained of pain, diarrhea, and/or weight loss at presentation, neither of them experienced vomiting or feculent eructation. A review of 46 of the 63 reported cases of gastric and duodenal fistulization indicated that patients with gastric fistulas commonly present with vomiting (39%), and with histories of feculent eructations or frank feculent vomiting (44%), but that patients with duodenal fistulas rarely present with vomiting (3.6%), and never have feculent vomiting or eructations. This difference is an important clue to the diagnosis and localization of upper gastrointestinal fistulas in Crohn's disease. PMID- 2327390 TI - Total gastrectomy after shunt failure as therapy for recurrent gastric variceal bleeding due to portal and mesenteric vein thrombosis. AB - A 37-yr-old man with portal hypertension due to portal vein thrombosis was referred because of recurrent episodes of variceal hemorrhage. He had previously undergone two portal-systemic shunt procedures. Both of the shunts, as well as the superior mesenteric vein, ultimately thrombosed. Endoscopic variceal sclerotherapy was able to control the bleeding from his esophageal varices, but he repeatedly bled from large gastric varices. The patient underwent a total gastrectomy and has had no further gastrointestinal hemorrhage during a follow-up of 36 months. PMID- 2327392 TI - Response to Dr. Mogadam. Importance of diet in the prevention of cancer. PMID- 2327393 TI - Spectrum of pancreatic disorders in patients with the acquired immune deficiency syndrome. PMID- 2327391 TI - Fatal submassive necrosis of the liver associated with piroxicam. AB - A 64-yr-old woman developed acute hepatitis after 3 wk of treatment with 40 mg/day of piroxicam (Feldene). Jaundice was preceded by a skin rash associated with eosinophilia. Despite withdrawal of the drug, she developed severe hepatocellular failure and died 53 days after the onset. Hepatitis was attributed to piroxicam because of the absence of other etiological factors. PMID- 2327394 TI - Acute hemolytic anemia and biliary colic as presenting manifestations of Wilson's disease. PMID- 2327395 TI - Pseudomonas aeruginosa bacteremia associated with sphincter of Oddi manometry. PMID- 2327396 TI - Refractory esophageal candidiasis in acquired immune deficiency syndrome (AIDS). PMID- 2327397 TI - Enteromonas hominis incidence and diarrhea. PMID- 2327398 TI - Repair of anal stricture after Whitehead operation. PMID- 2327399 TI - Cigarette smoking, blast crisis, and survival in chronic myeloid leukemia. AB - We reviewed the records of all patients with chronic myeloid leukemia (CML) seen in the CML Clinic of the University of Colorado Health Sciences Center between 1968 and 1987 for a history of cigarette smoking. Patients who smoked for five or more pack/years within the ten years preceding, or after the diagnosis of CML, were defined as smokers. Adequate smoking histories were obtained on 122 patients. Eighty-seven of these were non-smokers and 35 were smokers by the above criteria. The smoking group had a higher predominance of males, an older median age, and were diagnosed earlier in the course of the 20 year study. Seventy-two patients had died at the time of analysis. All but one, a non-smoker, died from the development of blast crisis. The overall median actuarial survival was significantly reduced for smokers (35 months) as compared to non-smokers (47 months). This was particularly striking for patients who had succumbed to the disease, with a median survival of 30 months in smokers versus 46 months in non smokers. Although various explanations could explain the differences noted, we conclude that cigarette smoking has an adverse effect on the development of blast crisis and survival in chronic myeloid leukemia. PMID- 2327400 TI - Effect of novel 1-alkyl-3-hydroxy-2-methylpyrid-4-one chelators on uptake and release of iron from macrophages. AB - The effect of several iron chelators on iron uptake and release by mouse peritoneal macrophages has been investigated. The 1,2-dimethyl (L1) and 1-ethyl-2 methyl (L1NEt) derivatives of 3-hydroxypyrid-4-one markedly enhanced iron mobilisation from macrophages pulsed with 59Fe-transferrin-antitransferrin immune complexes and were more effective than desferrioxamine, maltol, or mimosine. Release increased with increasing chelator concentration. None of the chelators donated significant amounts of iron to macrophages, and none showed any cytotoxic effect. The synthetic alpha-ketohydroxypyridine chelators may therefore be active in removing iron from the reticuloendothelial system as well as from hepatocytes, and indeed may be superior to desferrioxamine. PMID- 2327401 TI - Myelodysplastic syndromes: a study of surface markers and in vitro growth patterns. AB - A study of surface markers and in vitro growth in semi-solid and liquid medium was performed in 35 patients with newly diagnosed myelodysplastic syndrome (MDS). Surface markers were studied by CD34, CD13, CD14, CD15, and CD33 monoclonal antibodies. There was no strict correlation with the FAB typing, but CD34 was expressed only in refractory anemia with excess of blasts (RAEB) or RAEB in transformation (RAEB-t). CD14 was markedly positive in the 4 cases of chronic myelomonocytic leukemia. Colony-forming cells were assessed by culture in semi solid medium in the presence of HTB9 as growth factor. Four growth patterns were identified: a) normal growth (6 cases); b) no growth or low plating efficiency (10 cases); c) low colony and high cluster number (15 cases); and d) normal or high colony number with high number of clusters (4 cases). Expression of CD34 was associated with low colony and high cluster number. Finally we studied the proliferation and differentiation capacities in liquid culture without stimulating factor. Fifteen patients had a spontaneous proliferation. This was not correlated with any surface marker. Differentiation assessed by the loss of CD34 and/or the increase of CD15 by more than 20% at day 7 was observed in 21 cases. None of the surface markers or growth patterns was associated with a specific chromosomal abnormality, except the lack of growth in liquid culture observed in all 5q deletion cases. In univariate analysis, RAEB and RAEB-t FAB subtypes, percentage of blasts higher than 5%, staining by CD33 and CD34, and lack of differentiation in liquid culture were significantly associated with progression to leukemia and shorter survival. In multivariate analysis, only CD34 expression (P = .002) and percentage of blasts (P = .05) remained independent significant variables. CD34 was the only significant variable for prediction of survival (P = .05). It is concluded that surface marker analysis at diagnosis and after liquid culture may be a useful tool for the initial evaluation of MDS. PMID- 2327402 TI - Leukemic transformation in polycythemia vera: analysis of risk factors. AB - Forty-eight patients with polycythemia vera (PV) were retrospectively studied for incidence of acute leukemia over a 12 year period. Initial clinical features, hemogram, RBC mass, B12 levels, neutrophil alkaline phosphatase (NAP), and therapy given were studied for association with development of acute leukemia. There were 25 males and mean age at diagnosis was 61.4 years. Initial Hg was 18.38 +/- 1.86 g/dl, WBC 16.44 +/- 12.92 (x 1,000/mm3), platelets 632.94 +/- 303.81 (x 1,000/mm3), B12 1,030.93 +/- 445.20 pg/ml, and neutrophil alkaline phosphatase (NAP) score 136.63 +/- 55.14. Twenty-three patients were treated with phlebotomy alone and 25 received additional myelosuppressive therapy as follows- 2 received p32 alone, 4 alkylating agents alone, 8 hydroxyurea (HU) alone, and 11 received 2 or more (multiple) of these agents. None of those treated with phlebotomy alone but 6 of 25 (24%) patients given myelosuppressive therapy developed acute leukemia (P = .03) after a mean period of 46.8 months from start of myelosuppressive therapy. Four of the 11 patients (36%) receiving multiple agent therapy developed acute leukemia (P = .019). Initial hemoglobin levels, but not the other clinical parameters, were significantly higher in patients who developed acute leukemia (P = .002), and this difference persisted in various subgroups receiving myelosuppressive therapy. Thus, high initial hemoglobin and use of any myelosuppressive therapy are associated with an increased risk of leukemic transformation in polycythemia vera. This risk becomes substantial with the use of two or more myelosuppressive agents. Since myelosuppressive therapy does not prolong survival, its role in the management of polycythemia vera should be reexamined. PMID- 2327404 TI - Rapid reduction of methemoglobin in rat bone marrow erythroid cells. AB - Methemoglobin reduction was shown to proceed much more rapidly in erythroid cells from rat bone marrow than in rat erythrocytes. Methemoglobin reduction in suspensions of intact, nitrite-treated bone marrow cells does not depend on the presence of glucose in the incubation mixture, even after the cells have been stored in substrate-free medium. 2-Deoxyglucose and iodoacetate prevent the reduction from proceeding to completion. The results suggest that, relative to erythrocytes, immature erythroid cells more efficiently catalyze methemoglobin reduction and more effectively store metabolites which provide electrons for this reaction. PMID- 2327403 TI - 5' Nucleotidase in chronic B cell leukemias: a cytochemical and ultrastructural study. AB - We studied by cytochemical means the distribution of 5' nucleotidase (5' NT), a purine degradative enzyme, in the circulating lymphocytes of 24 healthy donors and 41 cases of chronic lymphoid leukemias, classified according to morphological and immunological criteria. About half the normal circulating lymphocytes were 5'NT positive and exhibited variable degrees of enzyme activity. Among chronic B lymphocytic leukemias we found high percentages of positive cells only in the phenotypically more mature cases. Moreover all cases of hairy cell, follicular cell, lymphoplasmacytic, and plasma cell leukemia showed moderate or weak 5' NT reactivity. Also one case of chronic T lymphocytic leukemia, CD8 positive, was moderately positive, while another, with large granular lymphocyte morphology, was completely negative. Electron microscopy revealed a discontinuous, granular plasma membrane reaction pattern, varying in intensity from case to case. In conclusion, our results confirm the usefulness of the 5' NT cytochemical reaction for identification of lymphoid populations at different stages of maturation in chronic B cell disorders. PMID- 2327405 TI - Phase II trial of alpha-tocopherol (vitamin E) in the treatment of primary systemic amyloidosis. AB - Primary systemic amyloidosis (AL) is a rare disorder characterized by deposition of a monoclonal immunoglobulin light chain or fragment thereof, resulting in dysfunction of the heart, kidney, liver, or nerves. Despite the use of melphalan, prednisone, colchicine, and dimethyl sulfoxide (DMSO), no improvement in median survival has been reported in prospective randomized studies. We undertook a study of alpha-tocopherol acetate (vitamin E) in the treatment of 16 patients with AL because of its reported benefits in animal models of senile and secondary amyloidosis as well as reported benefit in the treatment of secondary amyloidosis in humans. None of the patients showed any objective regression of their disease. The median survival of the entire group was 19.4 months. This survival is not superior to that reported with other agents used in this disease. We conclude that alpha-tocopherol is not a valuable agent in the treatment of AL. PMID- 2327406 TI - Neutrophilic myelofibrosis presenting as Philadelphia chromosome negative BCR non rearranged chronic myeloid leukemia. AB - Chronic myeloid leukemia consists of Philadelphia chromosome positive disease in 90% of cases, and a further 5%, although Philadelphia chromosome negative, exhibit bcr gene rearrangements consistent with the disease. The remaining 5% of cases have a heterogeneous clinical picture with a course unlike that of classical chronic myeloid leukemia, and may belong to different pathologic entities. We report five cases belonging to the latter group, initially identified as Philadelphia chromosome negative, bcr non-rearranged chronic myeloid leukemia, that developed progressive leucocytosis, absolute monocytosis, myelodysplasia, extramedullary hematopoiesis, and had evidence of myelofibrosis. These cases may represent a distinct clinical entity characterized by neutrophilic myelofibrosis, which can be identified prospectively by clinical and pathologic criteria. Standard therapy for treating chronic myeloid leukemia or idiopathic myelofibrosis may not be appropriate for this group. PMID- 2327407 TI - Patient with pyruvate kinase deficiency developed acute myelogenous leukemia. AB - A 44-year-old previously healthy male was diagnosed as anemic and treated at a nearby hospital. A year later, he was admitted to our hospital for precise examination of the progression of refractory anemia. Blood examination showed hemolytic anemia and more detailed examination of this hemolysis revealed pyruvate kinase deficiency. The activity was 15.1% of a normal control. Pyruvate kinase activities of his family members were normal or slightly decreased. Ten months after admission to our hospital, 2% of blast cells with Auer's body in the peripheral blood were noted which increased progressively. The bone marrow contained 17.3% of blast cells with a subsequent diagnosis of acute myelogenous leukemia being made. Although intensive chemotherapy was performed, the patient achieved a brief remission and died 2 years after admission to our hospital. PMID- 2327408 TI - Porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukemia. AB - A case of porphyria cutanea tarda (PCT) occurring after bone marrow transplantation (BMT) is reported. A 43-year-old male with chronic myelogenous leukemia received an human leukocyte antigen (HLA)-identical allogeneic transplantation with T-cell depleted marrow. Because of graft rejection, a second transplant was performed 4 months later. A grade II acute graft- vs.-host disease and a cytomegalovirus (CMV) infection were subsequently observed. Two years after the second transplant, cutaneous symptoms of PCT with typical biochemical abnormalities developed. Liver biopsy revealed signs of hepatitis with iron overload. CMV was isolated from liver tissue. The possible roles of underlying disease, BMT, and CMV liver disease are discussed in view of the recently reported cases of PCT in patients with AIDS or hematological disorders. PMID- 2327409 TI - Cyclosporin for treatment of life-threatening alloimmunization. AB - We describe a 16-year-old girl with aplastic anemia who, 1 year after initial diagnosis developed a refractory state to platelet transfusions due to alloimmunization and resulting in severe bleeding. Treatment with cyclosporin, initially prescribed as treatment of the bone marrow failure, resulted in prompt decrease in lymphocytotoxic antibodies, which paralleled a marked improvement in platelet recovery. To our knowledge, such a dramatic effect of cyclosporin on alloimmunization has not been previously reported and merits further attention. PMID- 2327410 TI - Synergistic effect of recombinant human erythropoietin and phorbol diester in platelet production by the human megakaryoblastic leukemia cell line (MEG-01) PMID- 2327411 TI - No beneficial effect of splenectomy in hereditary high red cell membrane phosphatidylcholine hemolytic anemia: clinical and membrane studies of 20 patients. AB - The clinical features and red cell membrane characteristics of 20 patients with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) were studied in relation to the effect of splenectomy. After splenectomy, anemia worsened and the extent of increased hemolysis in these patients was unchanged, indicating a contraindication for splenectomy. Concomitant with these results in clinical hematology, marked stomatocytic changes, increased red cell phosphatidylcholine content, and enhanced sodium transport, which were observed before splenectomy, were not improved by splenectomy. PMID- 2327412 TI - Mortality patterns of American merchant seamen 1973-1978. AB - Among 1,922 deaths in the American merchant marine population who were patients in the United States Public Health Service Hospital system in 1973-78, 46% were cancer associated. Eighteen percent of all deaths were due to heart disease. This pattern represented a reversal of the pattern found among patients of acute general care hospitals nationwide for the year 1975. Respiratory cancer amounted to 19.3% of the total, more than twice the number of such deaths among non-seamen patients. These patterns were consistent across a six-year time period. The finding in this study of an excess of cancer-associated deaths, particularly respiratory cancer, could be indicative of an occupationally associated risk. Data on the total population of merchant seamen at risk and of seamen deaths which may have occurred outside of the United States Public Health Service Hospital system are required to test more definitely the hypothesis of an occupational risk of cancer--especially lung cancer--among American merchant seamen. PMID- 2327413 TI - Spontaneous abortions among women exposed to organic solvents. AB - We investigated the association between medically diagnosed spontaneous abortions and occupational exposure to organic solvents. The study population was composed of women biologically monitored for solvents. The workers were classified into exposure categories on the basis of work description and the use of solvents as reported in the questionnaires, and on biological exposure measurements. The odds ratio of spontaneous abortion for solvent exposure, adjusted for potentially confounding factors, was significantly increased (2.2, 95% confidence interval [CI] = 1.2-4.1). The increase was most consistent among workers exposed to aliphatic hydrocarbons: the odds ratio for high exposure was 3.9 (95% CI = 1.1 14.2) and for exposed graphics workers 5.2 (95% CI = 1.3-20.8). The odds ratio was increased also among toluene-exposed shoe workers (9.3, 95% CI = 1.0-84.7). The results of the study support the hypothesis of a positive association between spontaneous abortion and exposure to organic solvents during pregnancy and suggest that exposure, especially to aliphatic hydrocarbons, increases the risk of abortion. PMID- 2327414 TI - Occupation and industry on death certificates of long-term chemical workers: concordance with work history records. AB - This study evaluated the concordance between occupation and industry listed on death certificates with actual work history information for a group (n = 5,882) of long-term (10 years or more) workers at a chemical company. Match rates were calculated as the percent of death certificate occupation and company entries that were confirmed by work history data using 3-digit 1980 U.S. Census Bureau group codes. The concordance rate for industry differed by employment status at death: employed, 94.9%; inactive, 30.8%; and retired, 91.1%. Concordance on occupation was analyzed for employed (n = 467) and retired (n = 932) subjects who had computerized work histories (randomly done prior to the study) and who had matched on the company on the death certificate. Concordance ranged from 0 to 50% for the first job, to 50 to 70% for the last job, longest job, and longest job in the last 10 years of company employment. The most consistent predictor of concordance was job duration. Misclassification was reviewed by occupational category. Results from this and other investigations lead to the inevitable conclusion that usual occupation data from death certificates are grossly inadequate for studies of occupational risks. PMID- 2327415 TI - Investigation of a lung cancer cluster in the melt shop of an Ontario steel producer. AB - Workers' concerns about an excess of cancer in an electric arc steelmaking operation were investigated. In comparison with men who had worked elsewhere in the plant, an increased risk of lung cancer death was observed among men who had been employed in the melt shop. The hypothesis that the association might be related to occupational exposures is supported by the persistence of the association when the hypothesis-generating cases were removed from the analysis (p = 0.063) and by a significant trend in the risk of lung cancer with years of exposure in the melt shop. No air sampling had been performed in earlier years. Current environmental analyses in the melt shop found no polycyclic aromatic hydrocarbons (detection limit: 0.001 mg/m3), and silica levels were below 0.1 mg/m3. The carcinogenic metals arsenic and chromium were detected, but their concentrations in earlier years are unknown. PMID- 2327416 TI - Cohort mortality study of Seattle fire fighters: 1945-1983. AB - Fire fighters are known to be occupationally exposed to many toxic substances. However, the limited number of previous studies has not demonstrated any consistent excess mortality from diseases of a priori concern, such as lung cancer, non-malignant respiratory disease, and cardiovascular disease. We studied 2,289 Seattle fire fighters from 1945 through 1983, and observed 383 deaths. Excess mortality from leukemia (SMR = 503, n = 3) and multiple myeloma (SMR = 989, n = 2) was observed among fire fighters with 30 years or more fire combat duty. Lung cancer mortality was elevated (SMR = 177, n = 18) among fire fighters 65 years old or older. We also analyzed the data by considering fire fighters at risk only after 30 years from first exposure. In this analysis, a trend of increasing risk with increasing exposure was observed for diseases of the circulatory system. For this cause of death, fire fighters with 30 years or more fire combat duty had a relative risk of 1.84 compared to those with less than 15 years of fire combat duty. PMID- 2327417 TI - Morbidity and mortality in talc-exposed workers. AB - Cancer incidence and cause-specific mortality were studied in a male cohort of 94 talc miners and 295 talc millers, exposed to non-asbestiform talc with low quartz content. No excess risk was found compared with national age-specific incidence. Six cases of lung cancer occurred versus 6.49 expected (miners: observed 2, expected 1.27; millers: observed 4, expected 5.22). There were 3 deaths due to non-malignant respiratory disease against 10.9 expected (miners: observed 1, expected 2.5; millers: observed 2, expected 8.4). Mesothelioma, tuberculosis, or pneumoconiosis were not recorded as causes of death. Pneumoconiosis was noted as a contributory cause in three cases (silicosis two, talcosis one). Further follow up will reduce any potential impact of "healthy worker" selection. PMID- 2327418 TI - Re: "Medical-Examiner-Reported Fatal Occupational Injuries, North Carolina, 1978 1984". PMID- 2327419 TI - Cocaine-related medical problems: consecutive series of 233 patients. AB - PURPOSE: Little information describing common cocaine-related medical problems is available. This study examined the nature, frequency, treatment, incidence of complications, and emergency department deaths of patients seeking medical care for acute and chronic cocaine-associated medical problems. PATIENTS AND METHODS: A consecutive series of 233 hospital visits by 216 cocaine-using patients over a 6-month period during 1986 and 1987 was studied. Medical records were retrospectively reviewed to determine patient characteristics, nature of complications, treatment, and outcome. RESULTS: Patients most commonly used cocaine intravenously (49%), but freebase or crack use was also common (23.3%). Concomitant abuse of other intoxicants, especially alcohol, was frequently seen (48.5%). The vast majority of complaints were cardiopulmonary (56.2%), neurologic (39.1%), and psychiatric (35.8%); multiple symptoms were often present (57.5%). The most common complaint was chest pain though rarely was it believed to represent ischemia. Altered mental status was common (27.4%) and ranged from psychosis to coma. Short-term pharmacologic intervention was necessary in only 24% of patients, and only 9.9% of patients were admitted. Acute mortality was less than 1%. CONCLUSION: Most medical complications of cocaine are short-lived and appear to be related to cocaine's hyperadrenergic effects. Patients usually do not require short-term therapy or hospital admission. Acute morbidity and mortality rates from cocaine use in patients presenting to the hospital are very low, suggesting that a major focus in the treatment of cocaine-related emergencies should be referral for drug abuse detoxification and treatment. PMID- 2327420 TI - Youthful precursors of alcohol abuse in physicians. AB - PURPOSE: This study was designed to determine youthful precursors of alcohol abuse in physicians. SUBJECTS AND METHODS: We analyzed data from an ongoing prospective study of 1,014 male medical students enrolled in the graduating classes of 1948-1964 at the Johns Hopkins School of Medicine. The cohort, now physicians aged 52 to 68 years, has been contacted regularly since medical school to identify major disease. In 1986, the CAGE alcoholism screening questionnaire was administered. Alcohol abuse was defined as self-admitted alcoholism, excessive consumption of four or more beverages per day on average, or a score of 2 or higher on the CAGE questionnaire. RESULTS: By these criteria, 131 of 1,014 (12.9%) patients abused alcohol. Medical school precursors associated (p less than 0.05) with subsequent alcohol abuse were as follows: non-Jewish ancestry (relative odds [RO] = 3.1), lack of religious affiliation (RO = 4.1), cigarette use of one pack or more per day (RO = 2.6), regular use of alcohol (RO = 3.6), anxiety (RO = 1.8) or anger (RO = 1.8) as a reaction to stress, frequent use of alcohol in nonsocial settings (RO = 1.6), past history of alcohol-related difficulty (RO = 3.1), and maternal alcoholism or mental illness (RO = 1.9). Precursors found not to be associated with alcohol abuse included sleep habits, use of sedatives or amphetamines, interest in athletics or hobbies, and parental relationship. CONCLUSION: Our results suggest that there are several identifiable medical school precursors of alcohol abuse in physicians. PMID- 2327421 TI - Intravenous adenosine triphosphate during wide QRS complex tachycardia: safety, therapeutic efficacy, and diagnostic utility. AB - PURPOSE: Inappropriate administration of intravenous verapamil to patients with wide QRS complex tachycardia due to ventricular tachycardia or atrial fibrillation with Wolff-Parkinson-White syndrome occurs frequently because of misdiagnosis, and may precipitate a cardiac arrest. We evaluated the safety and the diagnostic and therapeutic utility of adenosine triphosphate administered to a consecutive series of 34 patients during wide QRS complex tachycardia due to a variety of mechanisms. PATIENTS AND METHODS: Patients who had a hemodynamically and electrically stable, monomorphic, wide (greater than 120 msec) QRS complex tachycardia induced during an invasive cardiac electrophysiologic test were studied. Hemodynamic stability was defined by a systolic blood pressure greater than 80 mm Hg and no clinical evidence of cerebral or myocardial ischemia. Adenosine triphosphate, 20 mg, was administered as a rapid intravenous bolus via a peripheral vein during wide QRS complex tachycardia. Five surface electrocardiogram leads, at least three intracardiac electrograms, and blood pressure were monitored. RESULTS: Ventricular tachycardia was present in 14 patients (mean age 50.6 +/- 19 years, cycle length 326 +/- 67 msec) and adenosine triphosphate terminated the arrhythmia in one case. Ventricular tachycardia cycle length did not change. Among 10 patients with supraventricular tachycardia with mechanisms not involving the AV node (average ventricular cycle length 346 +/- 82 msec), one case of ectopic atrial tachycardia was terminated. The ventricular rate was transiently increased in patients with Wolff-Parkinson-White syndrome and atrial fibrillation (average R-R interval 351 +/- 84 msec in control and 317 +/- 82 msec after adenosine triphosphate, p less than 0.001). Reentrant tachycardias involving the AV node (cycle length 302 +/- 52 msec) terminated in seven of 10 patients. The drug was well tolerated, and no patient developed hemodynamic compromise necessitating cardioversion as a result of adenosine triphosphate. CONCLUSION: In the setting of electrophysiology testing, adenosine triphosphate is a safe agent, even when administered inappropriately during arrhythmias for which it is relatively ineffective, such as ventricular tachycardia, and Wolff-Parkinson-White syndrome with atrial fibrillation. It is an effective agent in terminating supraventricular tachycardia involving the AV node. Tachycardia termination following adenosine triphosphate, when used as a diagnostic test to indicate obligatory participation of the AV node, had a sensitivity of 70%, specificity of 92%, and a positive predictive accuracy of 85%. Thus, adenosine triphosphate also has diagnostic utility, but should be used after the appropriate arrhythmia diagnosis has been made based on the clinical history and analysis of the 12-lead electrocardiogram. PMID- 2327422 TI - Percutaneous-endoscopic biliary stenting in patients with occluded surgical bypass. AB - PURPOSE: The purpose of this investigation was to test the feasibility of using a recently developed technique of placing internalized biliary stents into patients who have had reobstruction after initial surgical bypass. PATIENTS AND METHODS: Seven men and three women, 46 to 85 years of age (eight with pancreatic carcinoma, one with metastatic colon, and one with metastatic ovarian carcinoma), all had reobstruction after initial surgical bypass palliation. Subsequent attempts to place stents via endoscope failed in five patients; a pair of 7-Fr stents placed in one patient failed to drain well. Endoscopic stenting in four patients was not even attempted because of severely distorted anatomy. Nine of the 10 patients then had successful internal stent placement by a combined percutaneous-transhepatic and peroral-endoscopically guided technique. RESULTS: One of these nine placeable stents failed to drain well and the patient died 8 days later with massive tumor. Seven showed a significant decrease in bilirubin levels and improved quality of life. Two of these had sepsis that responded to antibiotics. Life span ranged between 11 days and 10 months, with one patient still alive; no deaths were directly due to stents. CONCLUSION: A combined transhepatic-peroral technique of placing internalized biliary stents can be expected to result in repalliation in a majority of patients with reobstruction after earlier surgical bypass and in whom subsequent attempts at endoscopic placement of stents have failed or in whom tumor growth prevents undertaking the endoscopic approach. PMID- 2327423 TI - Altered water metabolism in tuberculosis: role of vasopressin. AB - PURPOSE: Patients with hyponatremia due to tuberculosis have shown variable responses to water loading in previous small studies, ranging from persistent antidiuresis to a normal diuresis. Although tuberculosis is considered a cause of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), circulating vasopressin has been documented in only a few cases. We studied a larger group of patients to determine whether it can be suppressed by a short-term reduction in osmolality. PATIENTS AND METHODS: Twenty-eight hyponatremic patients (mean age +/ SD: 40 +/- 10 years) with pulmonary or miliary tuberculosis underwent a clinical evaluation, measurement of blood and urine chemistry values, and (in 22) a water load of 20 mL/kg. Volume status was evaluated by urine sodium concentration, blood and urine urea nitrogen, and plasma renin activity. Endocrine, renal, and other recognized causes of SIADH were excluded. RESULTS: All 22 patients exhibited a decline in urine osmolality and an increase in free water clearance after water loading. Water excretion was fully normal in seven of 22, with the remainder showing variable impairment of diluting ability and/or volume excreted. Plasma vasopressin, measured in 11 of 22 patients as well as in six others not subjected to water loading, was detectable despite hypo-osmolality in 16 of 17. Vasopressin levels declined after water loading, from 1.85 +/- 1.32 to 0.77 +/- 0.25 pg/mL (p less than 0.05). The majority of patients had the euthyroid sick syndrome but normal adrenal responses to cosyntropin. Although several patients had mild volume depletion when studied, this factor did not appear to explain the defect in water excretion. Hyponatremia resolved predictably within days to weeks of antituberculous therapy. CONCLUSIONS: Circulating vasopressin remains detectable in hyponatremic patients with tuberculosis and is responsive to changes in osmolality. A downsetting of osmoregulation induced by active tuberculosis ("reset osmostat") could explain this abnormality, but we cannot exclude an unidentified non-osmotic stimulus that can be counteracted by water loading. PMID- 2327424 TI - Hemostatic complications in young patients with essential thrombocythemia. AB - PURPOSE: The purpose of this study was to determine the incidence of hemostastic complications in young patients with essential thrombocythemia (ET). PATIENTS AND METHODS: The clinical course of 44 patients under the age of 45 with the diagnosis of ET was reviewed in a retrospective manner. Patients were collected from three medical centers in the United States and Italy: the Brigham and Women's Hospital and the Harvard Community Health Plan, Boston, Massachusetts, and the Ospedali Riuniti di Bergamo, Bergamo, Italy. RESULTS: The overall incidence of hemorrhage or thrombosis, or both, in this group of patients was 39% (17 of 44), with serious complications occurring in 23% (10 of 44). Two patients died of thrombotic events. Neither the presence of symptoms at diagnosis nor any single laboratory parameter proved predictive of clinical sequelae. Treatment with antiplatelet drugs or platelet-lowering agents was not protective. CONCLUSION: We conclude that ET in young patients may result in serious and life threatening hemostatic problems and consequently that young age is not a favorable prognostic factor in this disease. PMID- 2327425 TI - Epidemiology of some peripheral arterial findings in diabetic men and women: experiences from the Framingham Study. AB - PURPOSE AND PATIENTS AND METHODS: The purpose of this study was to determine the relationship between diabetes and the development of some peripheral arterial findings--carotid and femoral bruits and nonpalpable pedal pulse--and acute cardiovascular events in 1,196 men and 1,582 women based on 20-year follow-up data in the Framingham Study. RESULTS: For both men and women without diabetes, the incidence of carotid bruits and nonpalapble pedal pulses increased significantly with age (p less than 0.05) without any apparent male predominance. In contrast, diabetic men and women were at an elevated risk of each peripheral arterial condition that was not appreciably different across age groups. Compared with women without diabetes, those with diabetes experienced nearly a twofold excess of femoral bruits (p less than 0.05) and a 50% excess of nonpalpable pedal pulses (p less than 0.01). Among men, diabetes nearly doubled the risk of carotid bruits (p less than 0.05). Those who had both diabetes and symptoms of peripheral arterial disease were at especially high risk of incident cardiovascular events. In particular, nonpalpable pedal pulses were associated with more than a twofold excess of coronary heart disease (p less than 0.05) and stroke (p less than 0.01) in diabetic women and more than a twofold excess of coronary heart disease and cardiac failure in diabetic men (p less than 0.01). Femoral bruits doubled the risk of coronary heart disease in diabetic men (p less than 0.05). CONCLUSION: We conclude that while diabetes predisposes to various forms and locations of peripheral arterial disease, the enhanced risk of acute cardiovascular events experienced by diabetic patients is increased further when diabetes is accompanied by indications of a peripheral arterial condition. Since signs of peripheral arterial disease may suggest an impending or coexistent atherosclerotic process, careful examination of arterial circulation by evaluating peripheral pulses and assessing whether bruits are present is important. PMID- 2327426 TI - Clinical findings associated with acute proximal deep vein thrombosis: a basis for quantifying clinical judgment. AB - PURPOSE: To identify clinical findings useful in estimating the probability of acute proximal deep vein thrombosis (DVT). PATIENTS AND METHODS: The records of 355 symptomatic patients who underwent ascending venography were reviewed. Data on 76 clinical items were collected using standardized forms. Venograms were interpreted according to standard criteria and interobserver agreement was evaluated in a sample of 119 venograms. Independent clinical correlates of proximal DVT were identified using multivariate discriminant analysis in 236 randomly chosen patients; they were tested in the remaining 119 patients. RESULTS: Acute proximal DVT was shown by venogram in 96 patients (27%). Five independent clinical correlates of proximal DVT--swelling above the knee of the affected leg, swelling below the knee, recent immobility, cancer, fever- predicted proximal DVT in the testing group; in patients with none, one, or two or more of these clinical findings, proximal DVT was present in 5%, 15%, and 42%, respectively. If venography had been performed only in patients with one or more of the five factors, 97% of cases of proximal DVT would have been diagnosed and venography would have been avoided in 26% of patients with normal test results. CONCLUSION: These data provide a quantitative basis for estimating the probability of proximal DVT on the basis of clinical findings in symptomatic patients. How these findings can best be integrated with noninvasive testing and venography into diagnostic strategies for DVT remains to be determined. PMID- 2327427 TI - Responsibility for patient care: where does the buck stop? PMID- 2327428 TI - Chyloptysis. PMID- 2327429 TI - Cocaine-associated asthma. PMID- 2327430 TI - Eosinophilic myocarditis associated with high-dose interleukin-2 therapy. PMID- 2327431 TI - Life-threatening hypercalcemia and tamoxifen. PMID- 2327432 TI - Electroconvulsive therapy and cyclophosphamide in combination for severe neuropsychiatric lupus with catatonia. PMID- 2327433 TI - Chronic acetaminophen ingestion associated with (1;7) (p11;p11) translocation and immune deficiency syndrome. PMID- 2327434 TI - Calcium antagonists and aminoglycoside nephrotoxicity. PMID- 2327435 TI - Prospective testing of fall risk index. PMID- 2327436 TI - Diagnosis and treatment of high-grade myeloma. PMID- 2327437 TI - Possible contraindication of angiotensin converting enzyme inhibitors in patients with hereditary angioedema. PMID- 2327438 TI - Sulfonylurea failure in non-insulin-dependent diabetes mellitus. PMID- 2327439 TI - Third-generation cephalosporins: a decade of progress in the treatment of severe infections. June 13, 1989. Proceedings. PMID- 2327440 TI - Are choroid plexus cysts an indication for second-trimester amniocentesis? AB - Previous series that described fetuses with choroid plexus cysts have been too small to determine whether there is an association with trisomy 18 sufficiently high to warrant amniocentesis. To address this issue, we studied the incidence of choroid plexus cysts and other ultrasonographic abnormalities in 26 consecutive fetuses (13.5 to 36 weeks' gestation) with trisomy 18. Twenty of these 26 fetuses had major sonographic anomalies suggestive of aneuploidy. Seventeen of these 26 fetuses were 15 to 20 weeks and 5 of 17 (30%) had choroid plexus cysts. Six of our total 26 affected fetuses had no sonographic anomalies and therefore, on the basis of our data, 30% of these (1.8 fetuses) with trisomy 18 would have choroid plexus cysts without other findings. The incidence of choroid plexus cysts in all second-trimester fetuses (including normal fetuses and those with trisomy 18) is reportedly 1%. Given the known incidence of trisomy 18 (3/10,000), we calculated a total presumptive sample of 86,667 patients to yield our 26 fetuses with trisomy 18. Our hypothetical sample has 86,641 (86,667 - 26) fetuses without trisomy 18,858 of which would have choroid plexus cysts. Thus there would be one fetus with trisomy 18 for every 477 normal fetuses with choroid plexus cysts with no other defect seen. If amniocentesis were done to seek trisomy 18 in all second trimester fetuses with choroid plexus cysts, two normal fetuses would be lost for every one with trisomy 18 identified. PMID- 2327441 TI - Significance of observing no fluid at amniotomy. AB - Thirty patients with oligohydramnios observed at artificial rupture of membranes were studied to determine the significance of this finding. Fifteen were subsequently found to have meconium-stained amniotic fluid and 21 had abnormal fetal heart rate tracings. This clinical observation warrants close intrapartum surveillance and preparation for delivery. PMID- 2327442 TI - Accelerated starvation in late pregnancy: a comparison between obese women with and without gestational diabetes mellitus. AB - We compared the glucose, insulin, free fatty acid, and 3-hydroxybutyrate responses to a briefly extended overnight fast during the third trimester of pregnancy between two groups: obese women with normal glucose tolerance (n = 10) and age- and weight-matched women with gestational diabetes mellitus (n = 10). After a 12-hour overnight fast, plasma glucose (95 +/- 4 vs. 78 +/- 2 mg/dl; p less than 0.01), insulin (32 +/- 5 vs. 17 +/- 2 microU/ml; p less than 0.02), and free fatty acid (860 +/- 63 vs. 639 +/- 79 mmol/L; p less than 0.05) levels were higher in the patients with gestational diabetes mellitus. 3-Hydroxybutyrate levels were similar in the two groups at that time (0.23 +/- 0.04 vs. 0.18 +/- 0.03 mmol/L; p greater than 0.3). When the fast was extended to 18 hours by having the patients skip breakfast, glucose levels fell more rapidly in the group with gestational diabetes mellitus but remained elevated compared with the nondiabetic women. Insulin levels declined at a similar rate in the two groups. Free fatty acid levels did not increase significantly in the group with gestational diabetes mellitus during the extended fast. In contrast, free fatty acid levels increased by 44% in the normal pregnant women, reaching the level observed in the group with gestational diabetes mellitus after 18 hours. 3 Hydroxybutyrate levels remained virtually identical in the two groups throughout the brief fast. Thus, compared with that of normal pregnant women, the response of obese women with gestational diabetes mellitus to brief caloric deprivation during late pregnancy was characterized by a greater fall in plasma glucose values without a greater propensity to ketosis. Our findings may have important implications for the dietary management of obese patients with gestational diabetes mellitus. PMID- 2327443 TI - Intrauterine fetal growth in concordant twin gestations. AB - We longitudinally assessed intrauterine ultrasonic growth parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) in 60 pairs of concordant twins. Head circumference to abdominal circumference and femur length to abdominal circumference ratios were calculated. Estimated fetal weight curves were created with the formula of Shepard et al., incorporating biparietal diameter and abdominal circumference, as well as that of Hadlock et al., incorporating femur length and abdominal circumference. Biparietal diameter was obtained in only 79% of fetuses, whereas femur length and abdominal circumference were obtained in 96% and 99% of fetuses, respectively. The intrauterine growth of abdominal circumference appears to be linear between 18 and 40 weeks, fitting the simple equation abdominal circumference = -4.5 + 0.97 gestational age (gestational age in weeks). The mean femur length to abdominal circumference ratio is 22.4 +/- 1.5 and appears to be gestational age independent between 20 and 40 weeks. The head circumference to abdominal circumference ratio decreases as gestational age advances in a linear fashion. Estimated fetal weight curves by the formulas of both Shepard et al. and Hadlock et al. fit second-order polynomial equations. Neither formula appears to be superior in estimating fetal weight in twin gestations, although that of Hadlock et al. can be used more frequently since biparietal diameter cannot always be obtained in both twins. PMID- 2327444 TI - Neonatal growth assessment score: a new approach to the detection of intrauterine growth retardation in the newborn. AB - To develop an improved means for evaluation of the outcome of fetal growth in utero, a growth study of 37 fetuses at risk for intrauterine growth retardation was undertaken. Intrauterine growth was evaluated with ultrasonography at 2- to 3 week intervals beginning at 15 weeks' gestation. Measurements obtained in the second trimester were used to specify Rossavik growth models for various anatomic parameters. Values for weight, head circumference, abdominal circumference, and thigh circumference at birth were predicted with the use of these models. Growth potential realization index values for these four parameters were calculated from actual and predicted birth measurements. The growth potential realization index values were combined to form a neonatal growth assessment score. With the use of cluster analysis and neonatal growth assessment score values, the 37 infants were separated into 24 group I (neonatal growth assessment score values between 3.7 and 18.6) and 13 group II (neonatal growth assessment score values between 19.4 and 50.0) infants. In group I, 66.7% of the infants had no growth abnormalities; a single abnormality, usually borderline, was found in an additional 20.8% (total = 87.5%). In group II all infants had growth abnormalities (range, 2 to 6) although only 46.2% had birth weights below the 10th percentile. No differences in risk factors (except for the incidence of smoking) or second trimester growth were found in these two groups. The neonatal growth assessment score appears to be a sensitive indicator of third trimester growth retardation, is not affected by differences in growth potential, can separate normal infants from those with evidence of intrauterine growth retardation, and provides a quantitative assessment of growth problems in individual fetuses. PMID- 2327445 TI - Prediction of preterm delivery: is it substantially improved by routine vaginal examinations? AB - The ability of routine vaginal examinations to improve the prediction of preterm delivery was assessed in a group of 6909 women who were registered at each prenatal visit and on whom this examination had been carried out. We compared two risk scores, one including known risk factors (maternal characteristics and symptoms reported by women), and the other including these factors and the findings of vaginal examination. These risk scores were computed by multiplying the adjusted odds ratio estimations obtained by logistic regressions. The prediction of preterm delivery was improved significantly by vaginal examination at 25 to 28 weeks' and 29 to 31 weeks' gestation. However, the improvement was not very large: when 30% of nulliparous women were classified as high risk at 29 to 31 weeks, the sensitivity was 55% when considering only the risk factors and 63% when adding the findings of vaginal examination; the percentages were 52% and 55%, respectively, for parous women. These results partially explain why the medical practice of routine vaginal examinations varies from country to country. PMID- 2327446 TI - Postpartum cardiovascular complications after bromocriptine and cocaine use. AB - A case is presented of a postpartum woman in whom hypertension and pulmonary edema developed after administration of bromocriptine mesylate. Caution is advised when there is additional recent use of cocaine because of a suggested potentiating action of cocaine on the development of adverse cardiovascular and cerebral sequelae in postpartum patients who take bromocriptine. PMID- 2327447 TI - Prenatal diagnosis of valvar aortic stenosis by Doppler echocardiography and magnetic resonance imaging. AB - We present herein a case of valvar aortic stenosis diagnosed antenatally, using color and pulsed Doppler echocardiography and magnetic resonance imaging. The benefit and advantages of the use of magnetic resonance imaging, complementary to the Doppler echocardiography, are discussed. PMID- 2327448 TI - Vel isoimmunization in pregnancy. AB - A pregnancy complicated by Vel isoimmunization is presented. Despite known immunoglobulin G component and significant titer rise, hemolytic disease of the newborn was not present. The maternal and neonatal significance of Vel sensitization is discussed. PMID- 2327449 TI - Survival and cell acquisition rates after preimplantation embryo biopsy: use of two mechanical techniques and two mouse strains. AB - Two strains of mouse embryos at the four- and eight-cell stages had biopsy specimens obtained by means of two different mechanical techniques: aspiration and displacement. Embryos and biopsy specimen cells were evaluated for survival and development. Blastomere acquisition rates were significantly higher with the displacement biopsy technique; however, no difference in survival or developmental rates was found in blastomere biopsy specimens removed from either four-cell or eight-cell embryos. A maximum of one blastomere can be removed from a four-cell embryo, whereas three blastomeres can be taken at biopsy from an eight-cell mouse embryo without significantly affecting embryo development, although mouse strain differences were noted. Intact, viable, biopsied blastomeres will develop in vitro when cocultured with morphologically intact embryos. Births of live offspring after embryo biopsy are reported. PMID- 2327450 TI - In vitro induction of prolactin production and aromatase activity by gonadal steroids exclusively in the stroma of separated proliferative human endometrium. AB - Prolactin production by decidualized human endometrium has been demonstrated in organ explant cultures and presumed to be of stromal origin by immunocytochemistry and the presence of simultaneous stromal histologic changes. To test the hypothesis that endometrial prolactin production is exclusively of stromal origin, late proliferative human endometrium was separated into glands and stroma and cultured for 3 days. Confluent cultures were incubated with progesterone, 50 ng/ml; estradiol, 5 ng/ml; or both progesterone and estradiol for 4, 8, and 15 days. Prolactin concentration was measured at 2-day intervals by specific radioimmunoassay throughout a 15-day culture in all samples. Aromatase activity at 15 days was assayed by the production of tritiated water from 1 beta 3H-androstenedione. Possible contamination of gland cultures by stromal cells was controlled by the substitution of D-valine in the culture media. No prolactin was detected in the D-valine-treated gland cultures. Stromal cell cultures demonstrated increasing prolactin with continuous incubation with progesterone (15-day control: 11.28 +/- 0.91 ng/100 micrograms deoxyribonucleic acid versus 15 day progesterone: 245.8 +/- 4.24 ng/100 micrograms). Prolactin levels increased after progesterone was removed at day 4 and 8, reaching peak production 4 days later, followed by a steady decline. Estradiol induced a sustained increase in prolactin production even after withdrawal of steroids. Aromatase activity in gland cells exposed to steroids exhibited no change with time. Steroid-treated stromal cell cultures showed an increase in aromatase activity in all 15-day (controls: 21.6 +/- 0.7 pmol substrate converted per mg of deoxyribonucleic acid per 24 hours versus progesterone: 43.4 +/- 4.2 versus estradiol: 34.2 +/- 3.5 versus progesterone and estradiol: 47.5 +/- 2.4) but not in 4- or 8-day incubations. These studies support these conclusions: (1) nongestational endometrial prolactin is of stromal, not glandular origin; (2) stromal prolactin production is induced and maintained by progesterone: (3) stromal prolactin production is induced by estradiol but does not require continued exposure for maintenance; (4) aromatase activity is increased by long-term exposure to progesterone and estradiol in stroma but not in glands. PMID- 2327451 TI - Fetal hemodynamic and fetoplacental vascular response to exogenous arginine vasopressin. AB - Fetal hemodynamics and fetoplacental blood flow were measured in chronically instrumented ovine fetuses during intravenous infusion of arginine vasopressin. Vasopressin was infused at rates ranging from 1 to 300 ng/min/kg estimated fetal mass. This range of infusion rates produces plasma arginine vasopressin levels observed throughout a wide range of fetal stress. No maternal effects were observed at any infusion rates used in this investigation. Fetal heart rate declined linearly with the log of the infusion rate. Mean fetal arterial pressure showed a sigmoidal response to log arginine vasopressin infusion rate, reaching a plateau at 30 ng/min/kg. Umbilical vascular resistance increased throughout the entire range of infusion rates. Fetoplacental blood flow decreased with increasing infusion rate but decreased only 4% to 13% throughout the range of infusion rates that produce plasma arginine vasopressin levels commonly observed during fetal stress. Because umbilical vascular resistance continued to rise after arterial pressure reached a plateau, fetoplacental blood flow decreased 31% at the highest infusion rate. However, the plasma vasopressin level associated with this infusion rate is probably in excess of that associated with severe fetal distress. The fetoplacental vascular bed is, therefore, either relatively insensitive to arginine vasopressin, or is capable of autoregulation in the face of high circulating levels of arginine vasopressin. PMID- 2327452 TI - Oral contraceptives and infection rates. PMID- 2327453 TI - Intrapartum fetal asphyxia. PMID- 2327454 TI - Fetal umbilical blood gas values as diagnostic criteria. PMID- 2327455 TI - Umbilical vein oxytocin. PMID- 2327456 TI - Efficacy of prednisone treatment to prevent recurrent fetal death. PMID- 2327457 TI - Assessment of fetal response to exercise in pregnancy. PMID- 2327458 TI - Causes of the increase in ectopic pregnancy. PMID- 2327459 TI - Postpartum gentamicin dosing and endometritis. PMID- 2327460 TI - Ethics and reproduction. PMID- 2327462 TI - The abnormal fetal biophysical profile score. V. Predictive accuracy according to score composition. AB - The relationship between last abnormal biophysical profile score, in total and by variable composition, and a spectra of abnormal perinatal outcome end points was examined in 525 fetuses. Highly significant inverse relationships between last test score and outcome were observed; relationships were linear for most end points and exponential for perinatal mortality end points. For biophysical profile scores less than or equal to 6, 25 of the 26 possible variable combinations were observed, at varying frequencies. For a biophysical profile score of 6, the positive predictive accuracy for some end points was significantly higher with either nonreactive nonstress test/fetal tone absent or nonreactive nonstress test/absent fetal breathing movement, and significantly lower with absent fetal breathing movement and decreased amniotic fluid volume. For a biophysical profile score of 4, the positive predictive accuracy for some end points was significantly higher with nonreactive nonstress test/absent fetal breathing movement/decreased amniotic fluid and was significantly lower with absent fetal movement/fetal breathing movement/fetal tone. No significant variation was observed for a biophysical profile score of 2. These data indicate that not all abnormal biophysical profile scores are equal. PMID- 2327461 TI - Heterogeneity of antigen expression in advanced epithelial ovarian cancer. AB - Immunohistochemical techniques were used to evaluate the expression of six antigens (CA 125, TAG 72, CA 19-9, OVTL3, DF3, and transferrin receptor) in frozen sections from the primary tumor and metastases of 20 patients with epithelial ovarian cancer. Heterogeneous expression of most antigens was observed within a given tumor nodule, but in each patient the proportion of cells expressing an antigen was similar in the primary tumor and metastases. To explore the stability of the antigenic phenotype of individual cells, we studied CA 125 expression in an ovarian cancer cell line. Cells were separated into CA 125 positive and -negative groups using fluorescence-activated cell sorting. After the two groups of cells were recultured separately, only 38% of cells originally sorted as CA 125 positive still expressed CA 125, whereas 27% of cells sorted as CA 125 negative expressed CA 125. That cells may gain or lose CA 125 expression in culture suggests that expression of CA 125 by ovarian cancer cells is not a stable trait. PMID- 2327463 TI - Designing a schedule of progestin administration in the control of endometrial carcinoma growth in the nude mouse model. AB - We previously showed that combined treatment with tamoxifen and progestin was effective in arresting the growth of human endometrial carcinomas in the nude mouse model. After a 15- to 20-week tumoristatic period, the tumors began to regrow, reminiscent of the clinical situation. Lack of progestin sensitivity during the regrowth period appeared to reflect the absence of progesterone receptor. To test the prediction that intermittent progestin administration may circumvent the regrowth phenomenon, the effect of various doses of progestin on blood progestin levels, EnCa 101 tumor progesterone receptor profiles, and rate of tumor growth were examined. Whereas 1 mg progestin was ineffective in totally down-regulating tumor progesterone receptor, 2 and 5 mg doses resulted in the total disappearance of tumor progesterone receptor by 1 week followed by its reappearance at 5 to 6 weeks and 9 to 10 weeks, respectively. On the basis of these results we predict that intermittent progestin administration may result in better control of endometrial cancer growth in the nude mouse system. PMID- 2327464 TI - The impact of luteal phase inadequacy in an infertile population. AB - A retrospective analysis of patients evaluated and treated for infertility was performed. Luteal phase inadequacy was diagnosed when the late luteal endometrial biopsy pattern was greater than 2 days out of phase in two cycles; in patients treated with clomiphene citrate therapy was changed if one biopsy was out of phase. One hundred ninety-seven patients underwent 242 biopsies. Among 137 women no treated with clomiphene citrate, 24 (17.5%) had out-of-phase biopsy specimens; 7 of 24 (29.2%) repeat biopsies were out of phase, with luteal phase inadequacy in 7 of 137 (5.1%) women. The probability of an out-of-phase biopsy occurring by chance alone was 4.2 of 137 or 3.1%. No woman was diagnosed to have luteal phase inadequacy as the single infertility factor. Fifty-three pregnancies (41%) occurred in 130 women without luteal phase inadequacy and in 2 of 7 (28.6%) diagnosed to have luteal phase inadequacy with other infertility factors. In clomiphene citrate-treated patients, pregnancy occurred in 15 of 26 (57.7%) with corrected luteal phase inadequacy and in 21 of 34 (61.8%) without luteal phase inadequacy. In this population the diagnosis of luteal phase inadequacy was not made more frequently than by chance alone. Moreover, fecundity in patients with treated luteal phase inadequacy is comparable to that in patients without this diagnosis. PMID- 2327465 TI - Urinary incontinence in community-dwelling women: clinical, urodynamic, and severity characteristics. AB - Descriptive data on 145 community-dwelling older women with urinary incontinence are presented. Assessment included history, physical and functional examinations, and urodynamic and severity evaluations. Patients were 67 +/- 8 years old, mentally and functionally intact, predominantly white, and of middle-to-upper socioeconomic strata. Specific urodynamic criteria were used to establish the diagnosis of sphincteric incompetence and detrusor instability. Fifteen (10%) did not fulfill either criteria, 90 (62%) had sphincteric incompetence, 17 (12%) had detrusor instability, and 23 (16%) had both. Detrusor and urethral function variables showed some impairment in all patients. Impairment was least in subjects without demonstrable diagnosis and worst in those with both disorders (p less than 0.01). The findings suggest that detrusor and urethral functions are impaired in all incontinent women and that the degree of impairment varies. The impairment seems worse when both urodynamic diagnoses are demonstrable. The data support the pathophysiologic association of urethral and detrusor dysfunctions. PMID- 2327466 TI - Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas. AB - The incidence of leiomyosarcoma in uterine leiomyomas is estimated to be between 0.13 to 0.29%. However, the exact incidence of leiomyosarcoma in uteri removed with a preoperative diagnosis of benign uterine leiomyomas has not been previously reported. Between 1983 and 1988, a total of 1432 patients in Women's Hospital, a self-referred indigent population, had a hysterectomy planned because of abnormal uterine bleeding or abdominal pain associated with the presence of uterine leiomyomas, or because of a pelvic mass thought to be uterine leiomyoma of sufficient size or character to warrant surgical exploration. The ages of these women ranged from 36 to 62 years and the presence of leiomyosarcoma in the hysterectomy specimens increased steadily from the fourth to seventh decades of age (0.2%, 0.9%, 1.4%, and 1.7%, respectively). Preoperative histologic examination of the endometrium was performed in eight patients. Three of the eight patients had a preoperative tissue diagnosis of leiomyosarcoma that was clinically confined to the uterus. After the hysterectomy in the 1429 patients with presumed benign disease, histologic diagnosis of leiomyosarcoma was made in seven (0.49%). There was no evidence of malignancy in the endometrial sampling of any of these seven patients and the diagnosis was suspected intraoperatively in only three. Preoperative uterine size ranged from 8 to 20 weeks' gestational size and postoperative uterine weight ranged from 120 to 1100 gm. Seven of the 10 patients had symptoms of abnormal uterine bleeding. Between the ages of 40 and 60 years, 1% (8 of 817) of women with presumed uterine leiomyomas producing symptoms that necessitated hysterectomy in this series had leiomyosarcoma diagnosis postoperatively. Such treatments as gonadotropin-releasing hormone agonists, endometrial ablation, myomectomy by hysteroscopy or laparotomy instead of hysterectomy in such women could delay the diagnosis and definitive treatment of leiomyosarcoma. PMID- 2327467 TI - Fatal pulmonary embolism during legal induced abortion in the United States from 1972 to 1985. AB - To determine the risk factors for abortion-related deaths caused by pulmonary embolism, we investigated all deaths from legal abortions in the United States from 1972 through 1985. Of 213 deaths, 45 (21%) were due to air, blood clot, or amniotic fluid embolism. The risk of embolism death was higher among minority women and older women (34 to 44 years). Our analysis revealed that curettage at less than or equal to 21 weeks and abortions at less than or equal to 12 weeks, regardless of method, were both associated with the least risk of embolism death. In comparing 1972 to 1978 and 1979 to 1985, we found that the embolism mortality rate decreased 79%. During 1979 to 1985, the number of abortions performed by noncurettage methods decreased 58%, possibly as a result of earlier abortion morbidity studies, which showed that these methods carried a greater risk of complications. Although a decrease in mortality rates may be partially attributable to the declining use of these methods, our analysis suggests that changes in methods over time have not been universally applied to all racial groups. PMID- 2327468 TI - Vaginal bleeding and diethylstilbestrol exposure during pregnancy: relationship to genital tract clear cell adenocarcinoma and vaginal adenosis in daughters. AB - Comparing 186 cancer cases and 1772 cancer-free controls and reexamining several previously published studies, we found genital tract clear cell adenocarcinoma and vaginal adenosis to be moderately, but nonsignificantly, associated with vaginal gestational bleeding when in utero diethylstilbestrol exposure was statistically controlled. Considering the prevalence of diethylstilbestrol exposure in the general population, the relative risks of vaginal clear cell adenocarcinoma for in utero exposure were 365.6 and 459.0 when vaginal bleeding did and did not occur during the index pregnancy, respectively. The relative risks of vaginal adenosis for such diethylstilbestrol exposure were 15.4 and 92.8, respectively, for these women. The strong associations between in utero diethylstilbestrol exposure and both vaginal adenosis and genital tract clear cell adenocarcinoma cannot be attributed to the occurrence of problem pregnancy. However, among daughters exposed to diethylstilbestrol, maternal vaginal bleeding during the index pregnancy does appear to be associated with reduced risks of vaginal adenosis and vaginal clear cell adenocarcinoma. PMID- 2327469 TI - A rapid method to determine proliferation patterns of normal and malignant tissues by H3 mRNA in situ hybridization. AB - A general method applicable for the determination of any mammalian tissue's proliferative pattern is described. This method determines the cellular mRNA level of a proliferation-dependent gene, histone H3, by in situ hybridization. The cell-cycle S-phase-specific expression of this highly conserved ubiquitous cellular gene, and the lack of it in resting cells, permits the unambiguous identification of cycling cells in any tissues, normal or diseased. This method can be conveniently coupled with routine biopsy and could be streamlined for a central laboratory with results obtainable in 2 days. Furthermore, this procedure works successfully on formalin-fixed paraffin-embedded sections, thus allowing retrospective studies of biopsies or autopsy materials. PMID- 2327470 TI - Malignant melanoma simulants arising in congenital melanocytic nevi do not show experimental evidence for a malignant phenotype. AB - Proliferative neoplasms that resemble malignant melanoma may develop in large congenital melanocytic nevi, prenatally or in the neonatal period, although these lesions rarely show the progressive growth or behavioral characteristics of melanoma. This report describes the genetic, biologic, and immunologic characteristics of six tissue culture cell lines derived from two neoplasms present in congenital melanocytic nevi in two newborn infants. Both neoplasms had clinical and histologic features of malignant melanoma. Despite these features, cells from all lines were phenotypically benign, as evidenced by a normal karyotype, their expression pattern of pigment cell-associated antigens, absence of melanoma-associated ganglioside GD2, their mitogenic response to the tumor promoting phorbol ester 12-0-tetradecanoyl phorbol-13-myristate, their inability to grow anchorage independently in soft agar, and prolonged but finite life span. The cells did not produce tumors in nude mice, but they remained viable at the injection site for over 7 months. PMID- 2327471 TI - Pathogenesis of caprine arthritis encephalitis virus. Cellular localization of viral transcripts in tissues of infected goats. AB - Pathologic specimens of 18 goats with classical lesions of caprine arthritis encephalitis (CAE) virus infection were examined morphologically and by in situ hybridization using molecularly cloned CAEV deoxyribonucleic acid (DNA) to determine which tissues and cells of naturally infected goats supported virus replication. Large numbers of cells with viral transcripts were detected in inflamed brain, spinal cord, lung, joints, and mammary gland. These cells were morphologically compatible with macrophages. Fewer cells with viral transcripts were seen in noninflamed tissues. Viral RNA was identified in macrophagelike cells in lung, liver, spleen, and lymph nodes, in cells lining the vessels of brain and synovium, and in epithelial cells of intestinal crypts, renal tubules, and thyroid follicles. These data suggest that the cell tropism of lentiviruses may extend beyond the narrow boundaries of lymphocytes and macrophages. PMID- 2327472 TI - Trophoblast interaction with fibrin matrix. Epithelialization of perivillous fibrin deposits as a mechanism for villous repair in the human placenta. AB - The authors have used morphometric, immunocytochemical, and electron optical techniques to study fibrin deposits associated with villi from 14 normal term placentas, and have examined the response of cultured cellular trophoblast to fibrin matrix in vitro. Morphometric analysis of 3477 villous profiles showed that 5.5% of villi examined had fibrin deposition at sites of syncytial denudation and that fibrin deposition was highly associated with villous epithelial denudation, as evidenced by loss of cytokeratin staining. The perivillous fibrin deposits were strongly immunoreactive for the B beta chain of fibrin II, consistent with local thrombolytic cleavage of fibrinogen to fibrin. Deposits were frequently surfaced by a discontinuous layer of cytokeratin positive trophoblastic cells that showed type IV basement membrane collagen immunoreactivity at the interface between trophoblast and fibrin. Ultrastructurally, damage to the syncytial trophoblast was apparent at the edge of some deposits, where syncytial denudation was accompanied by a fibrin coating of residual cellular trophoblast and the trophoblastic basal lamina. Other deposits were surfaced by syncytial trophoblast with underlying cellular trophoblast and a new basal lamina external to the basal lamina of the villous core. Cultured cellular trophoblast grown on a fibrin matrix, but not on uncoated plastic, showed morphologic differentiation into a trophoblast layer like that on term villi. The authors suggest that epithelialization of perivillous fibrin deposits is a form of villous repair and that trophoblast-fibrin interactions can modulate trophoblastic differentiation. PMID- 2327473 TI - Phototoxic damage to sebaceous glands and hair follicles of mice after systemic administration of 5-aminolevulinic acid correlates with localized protoporphyrin IX fluorescence. AB - The skin of albino mice given 5-aminolevulinic acid (ALA) by intraperitoneal injection rapidly developed the characteristic red fluorescence of protoporphyrin IX. Fluorescence microscopy of frozen tissue sections revealed intense red fluorescence within the sebaceous glands and a much weaker fluorescence within the epidermis and hair follicles. Little or no fluorescence was detected in the dermis, blood vessels, or cartilage of the ear. Light microscopy of skin taken at intervals after whole-body exposure of ALA-injected mice to photoactivating light revealed destruction of sebaceous cells, focal epidermal necrosis with a transient acute inflammation, and diffuse reactive changes in the keratinocytes. The dermis showed transient secondary edema and inflammation. The location and severity of the phototoxic damage correlated well with the location and intensity of the red fluorescence. The light-exposed skin appeared to recover completely except for a persistent reduction in the number of hair follicles. PMID- 2327474 TI - Sequential events in the pathogenesis of streptococcal cell wall-induced arthritis and their modulation by bis(5-amidino-2-benzimidazolyl)methane (BABIM). AB - This report builds on the authors' earlier discovery of bis(5-amidino-2 benzimidazolyl)methane (BABIM) as a strong suppressive agent for streptococcal cell wall fragment-induced arthritis in the Lewis rat. As a synthetic inhibitor of trypsinlike proteases, BABIM opens up a new route to the control of inflammatory joint disease. To gain a deeper insight into the function of the compound, the authors have now studied its influence on the sequential development of the joint changes and the associated lesions in spleen and liver. Bis(5-amidino-2-benzimidazolyl)methane is shown to block acute synovitis, to retard and reduce granuloma formation in spleen and liver, to decrease neutrophilic leukocytosis, and to diminish hemopoietic hyperplasia in the bone, and thus also to mitigate the distinctive osteoclastic and chondroclastic events. The compound does not interfere with the splenic immune response, the temporary rise in hepatocytic mitotic activity, or the organ deposition of streptococcal cell walls. PMID- 2327476 TI - On the differences between two pelvises of Mousterian context from the Qafzeh and Kebara caves, Israel. AB - Two pelvises from a similar archaeological context have been discovered in recent years in two different caves in Israel. The pelvis from the Qafzeh cave (Qafzeh 9) was dated by means of thermoluminescence at approximately 95 kyr BP. All available measurement values, the most significant being those of the diagnostic obturator region, fall within those of the modern range. The other pelvis emanates from the Kebara cave and differs fundamentally from modern pelvises and from the Qafzeh specimen, although the Kebara pelvis is 30,000 years younger than the latter. As in other remains of Neandertal pelvises, the superior pubic ramus of the Kebara hominid is extremely long and slender and exhibits a cross section unlike that of modern humans. The absolute height of the obturator region is very small. It is these measurements and proportions that set the Kebara pelvis apart from both modern pelvises and the specimen from Qafzeh. The morphological differences and the chronological relationship between the two fossil pelvises support the concept of two distinct evolutionary lineages for these hominids. PMID- 2327477 TI - Longevity factor in hominoid social organization. AB - In most primate groups emigration of the maturing young of one or the other sex tends to serve as an incest avoidance mechanism. Among most primate species it is the males who change groups. This supports the theory that, in terms of reproductive success, males should compete for mates and females should compete for resources. In hominoids the combination of increased longevity and greater female discrimination in mate selection seems responsible for female emigration. This may relate to the high frequency of patrilocality and male control of resources among human groups. PMID- 2327475 TI - Effects of in vivo 'priming' on endotoxin-induced hypotension and tissue injury. The role of PAF and tumor necrosis factor. AB - Exogenously administered tumor necrosis factor-alpha (TNF) and bacterial endotoxin (LPS) induce shock and tissue injury. Here, the authors studied the effect of endogenous TNF on LPS-induced hypotension and tissue injury and investigated the role of PAF in these responses. Rats were primed with intraperitoneal injection of zymosan 24 hours before, or Bacillus Calmette-Guerin (BCG) 12 to 15 days before intravenous injection of low dose (0.5 mg/kg) LPS. It was found that nonprimed animals showed mild hypotension and moderate leukopenia in response to LPS. In contrast, zymosanprimed rats developed shock and marked leukopenia, and more severe bowel injury than nonprimed rats. The authors then showed that, following LPS injection, zymosan-primed animals had higher TNF and platelet-activating factor (PAF) levels than nonprimed rats. Pretreatment of the animal with PAF antagonist, SRI 63-441, markedly ameliorated the hypotension and tissue injury. Interestingly, BCG-primed rats did not show aggravation of LPS induced hypotension. Only TNF (but not PAF) level in these animals was increased. Thus, it appears that TNF release alone, without a sufficient increase in PAF, is incapable of causing severe hypotension. However, most of the BCG-primed animals showed tissue injury, which could be prevented by pretreatment with PAF antagonist. The authors discuss the possible mechanisms of this discrepancy between systemic and local responses in BCG-primed animals. PMID- 2327478 TI - Diversity of palmar pattern ridge counts in Iranian populations. AB - We analyzed bilateral palmar prints of 3,158 individuals from 13 Iranian populations of diverse origins for palmar pattern ridge counts. Right palms did not show greater counts than the left in the majority of the populations studied. Highly significant interpopulational variation was observed for most palmar areas of both males and females. Dendrograms of males and combined sexes showed a good fit with the ethnohistoric background of the populations studied. The results thus demonstrate variation in the palmar pattern ridge counts of populations of diverse origins and may be used as a good measure of population distance. PMID- 2327479 TI - Age variations in the relation of body mass indices to estimates of body fat and muscle mass. AB - In some chronic disease studies, distinctions have been made regarding the importance of body mass index (BMI) as a risk factor in younger versus older men and women. In order to determine the significance of these differences in BMI disease associations, we determined the extent of age-dependent variations in the relation of BMIs to body composition in large probability samples of U.S. men and women from the First and Second U.S. National Health and Nutrition Examination Surveys (NHANES I and II). BMIs are more highly correlated with estimates of body fat in younger than in older men and women, and with muscle mass in older than in younger adults. Caution should be exercised in interpreting the significance of BMI as a risk factor for chronic disease, particularly in comparison of age groups. PMID- 2327480 TI - Skeletal and dental pathology of free-ranging mountain gorillas. AB - The mountain gorillas of the central Virungas have been the subject of field study for the last 30 years; however, our understanding of morbidity and mortality in these apes is limited. This paper describes pathological conditions of the skeleton and dentition of these animals and evaluates lesions in relation to behavioral and environmental data. The skeletal remains of 31 mountain gorillas from the Karisoke Research Center were examined for enamel wear, carious lesions, abscesses, periodontal disease, antemortem tooth loss, trauma, inflammation, arthritis, neoplasia, and developmental anomalies. Two infants, three juveniles, 13 adult males, and 13 adult females form the sample. Enamel wear in the permanent posterior dentition is moderate. Six periapical abscesses were seen; three are associated with antemortem tooth breakage. No carious lesions were observed. Pronounced calculus buildup and alveolar resorption are the most notable pathological conditions of the dentition and affect all adult animals. The primary affliction of the skeleton is arthritis, which affects 14 animals. Vertebral degenerative disease predominates, but there is also temporomandibular joint involvement. Fractures occur at seven locations in the postcranium. In addition, there are five cranial injuries, including a fractured sagittal crest, and a penetrating wound to the vault, which is believed to result from a bite. Also thought to result from a bite is a case of cranial osteomyelitis. The only other inflammatory responses are two cases of idiopathic periostitis and one idiopathic lytic lesion. Button osteomas affect two animals and are the only neoplastic conditions observed. Two animals are afflicted by developmental abnormalities: one animal by idiopathic vertebral fusion and the other by spinal scoliosis. PMID- 2327481 TI - Partial humeri of two Miocene Colombian primates. AB - Distal portions of humeri from two Miocene Colombian primates were recovered during field work in 1986. The larger IGM 183420 is very similar in size and morphology to the humerus included in the type specimen of Cebupithecia sarmientoi, recovered from La Venta in 1945 (Stirton and Savage: Serv. Geol. Nac. Bogata 7:345-356, 1951) and is assigned to this taxon. IGM 183420 presents a number of features of the humerus associated with clinging postural behaviors in living platyrrhines, including a medial epicondyle with very little dorsal angulation, a cylindrical trochlea, and a contact facet for the coronoid process of the ulna. In these and other features Cebupithecia most closely resembles the extant genus Pithecia. IGM 183512 is approximately the size of Saimiri sciureus and is very similar in morphology to the humerus of this small arboreal quadruped. The medial epicondyle is more dorsally angled, the medial lip of the trochlea is more pronounced and the capitulum is less spherical as compared to Cebupithecia. This fossil is assigned to the taxon Neosaimiri fieldsi. PMID- 2327482 TI - Salivary measurement of episodic progesterone release. AB - Episodes of luteal progesterone release which have been identified from serum samples can also be observed in saliva. Components of these release episodes- amplitude, duration, and frequency--can be separated and characterized. In a sample of 16 cycle days collected from 6 normal women, pulse duration and frequency increased significantly from the early to the mid-luteal phase, and then decreased by the late luteal phase (2-4 days before menses). Pulse amplitude also increased early to mid-luteal, but continued to increase significantly into the late luteal, and did not decline until the peri-menstrual phase (0-1 days before menses). Circadian variation, previously considered unimportant for progesterone, was also observed in late luteal samples. Extension of studies of ultradian release characteristics to groups known to vary from controls in broad scale progesterone patterns, such as young, nutritionally stressed, or exercising women, should help to elucidate the potential functional significance of fine grained release components. Such knowledge can also inform protocols of anthropological studies which seek to identify broad progesterone patterns or to classify and compare reproductive status. PMID- 2327483 TI - Effects of size on vervet (Cercopithecus aethiops) gait parameters: a longitudinal approach. AB - Changes in the values of certain locomotor parameters were analyzed over a range of speeds for five immature vervet monkeys sampled at 6 month intervals over approximately a 3 year period. Lateral and diagonal sequence walking gaits and transverse and rotary gallops were commonly used. The monkeys switched from walking to galloping at long cycle durations for their mass, although, as a group, their transition speeds were in agreement with data from other mammals. However, for individual monkeys, transition speed was not consistently dependent on body mass. Cycle and stance durations generally increased with increasing size at each speed for each animal, with the greatest increases occurring at slower speeds. Swing durations increased slightly with size. For any particular individual, speed was highly predictable from cycle (or stance) duration and body mass (or age). However, the multiple regression equations for each animal were significantly different from each other, suggesting that no single equation is satisfactory for all of the individuals within a species. PMID- 2327484 TI - Effects of growth and speed on hindlimb joint angular displacement patterns in vervet monkeys (Cercopithecus aethiops). AB - Hip, knee, and ankle joint displacement patterns are compared across both age and speed for five immature vervet monkeys sampled approximately every 6 months over a 3 year period. The analysis indicated that, as a group, the animals displayed no consistent changes in joint patterns as they grew. However, individual animals showed consistent patterns. There were also no consistent effects of size across animals at the walk-gallop transition. This is contrary to McMahon's prediction (J. Appl. Physiol. 39:619-627, 1975) based upon his elastic-similarity model of animal scaling. With increasing speed, when symmetrical gaits were used, all of the animals tended to show a decrease in the relative positions of the hip, knee, and ankle maximum values. Furthermore, across the walk-gallop transition, the animals tended to show a decrease in the range of ankle and knee movements. PMID- 2327485 TI - Inverse relationship between defensiveness and lifetime prevalence of psychiatric disorder. AB - Defensiveness (the tendency not to report unfavorable information about oneself), as measured by the Marlowe-Crowne Social Desirability Scale, has been shown to be inversely correlated with self-reported symptoms. In this family study of depression, direct interviews with 380 subjects combined with relatives' reports revealed a similar inverse relationship between defensiveness and lifetime prevalence of any psychiatric disorder, especially when diagnostic status was most certain and among those at greater risk for psychopathology. The authors conclude that the Marlowe-Crowne scale measures a factor or trait associated with the relative absence of psychiatric disorder, not the underreporting or denial of disorder. PMID- 2327486 TI - Gender weighting of DSM-III-R personality disorder criteria. AB - This study explored the gender weighting of the diagnostic criteria for personality disorders. Gender weighting was defined in terms of how 33 female and 17 male nonclinicians ranked the diagnostic criteria along a male-female dimension. Although the a priori expectation was that antisocial would be the prototypically masculine personality disorder and histrionic the feminine, the subjects ranked criteria from the sadistic category as the most masculine and those from the dependent category as the most feminine. These results and the subjects' gender weighting of criteria for borderline, obsessive-compulsive, and self-defeating personality disorders are analyzed in detail. PMID- 2327487 TI - Suicide and schizophrenia: data from a prospective community treatment study. AB - This article reports the analysis of prospectively gathered data on eight young adults who committed suicide during an ongoing longitudinal study of long-term treatment of schizophrenia in the community. Young adult men with an early onset of psychiatric illness were identified as a high-risk subgroup. At the time of admission to the study, the subjects who eventually committed suicide reported significantly more distress and tended to be less satisfied with their lives than the other subjects. Specifically, baseline measures of self-reported subjective distress were consistently predictive of later suicide, whereas interviewer-rated measures and postbaseline assessments were not. PMID- 2327488 TI - Depressive episodes and dysphoria resulting from conjugal bereavement in a prospective community sample. AB - Using three waves of interviews from the New Haven Epidemiologic Catchment Area Program, the authors contrast the extent and nature of depressive episodes and dysphoria between newly bereaved (N = 39) and married (N = 1,047) respondents age 45 and older. Bereavement greatly increased the risk of both conditions. This observation did not appear to be an artifact because psychosocial risk factors were similar for the bereaved and married groups. Bereavement increased the risk for a depressive episode more among respondents who reported no prior dysphoria than among those who did. Among those meeting criteria for depression, the bereaved reported symptoms similar to those of the married group except for significantly fewer reports of guilt. PMID- 2327489 TI - Mortality in a group of formerly incarcerated juvenile delinquents. AB - A 7-year follow-up study of formerly incarcerated delinquents revealed an extremely high mortality rate. Of 118 male and female subjects, seven had died before their 25th birthdays, making the mortality rate of the sample approximately 58 times the national average for individuals in their age group. All died violent deaths, making the violent death rate of the sample approximately 76 times the national average for that age group. Differences in mortality rates according to the race and sex of the subjects are reported, and possible clinical predictors of early death are explored. PMID- 2327490 TI - Diagnosis and clinical course of erotomanic and other delusional patients. AB - Twenty-eight patients with erotomanic delusions were compared with 80 patients with other delusions to clarify questions about diagnosis and course of illness in erotomania. The erotomanic patients were a heterogeneous group with respect to both diagnosis and course. They had significantly more manic symptoms than the comparison group and more affective diagnoses than would be expected from the literature; 25% (N = 7) had schizoaffective disorder and 7% (N = 2) had bipolar disorder. A subgroup of monodelusional erotomanic patients was identified who met the DSM-III-R criteria for delusional disorder, thus supporting the decision to include erotomanic delusions in this diagnostic category in the revision of DSM III. PMID- 2327491 TI - Reduced dark-adaptation: an indication of lithium's neuronal action in humans. AB - Although lithium plays a major role in therapy and prophylaxis of affective psychoses, no direct indication of its neuronal action in humans exists. A lithium-induced strong reduction of foveal dark-adaptation was found in healthy volunteers, and a lithium-induced reduction was also measured in patients with affective psychoses. Dark-adaptation measurements apparently offer the opportunity for in vivo monitoring of lithium's CNS effects in humans and may predict lithium's clinical efficacy. PMID- 2327492 TI - Sexual and physical abuse histories and psychiatric symptoms among male psychiatric outpatients. AB - Of 125 consecutive male patients at an adult psychiatric outpatient clinic, 48% reported histories of sexual abuse and/or physical abuse. The mean scores on the global severity index of the SCL-90-R at the first visit were significantly higher for those who reported histories of abuse than for those who had no such history. Childhood abuse also was associated with high levels of psychiatric symptoms in these men. PMID- 2327493 TI - Major depression in patients with social phobia. AB - The authors examined the longitudinal course of affective illness retrospectively in 63 patients with social phobia and 54 patients with panic disorder. Significantly fewer (35%) of the patients with social phobia than patients with panic disorder (63%) had experienced at least one major depressive episode. Patients with generalized social phobia and patients with specific social phobia had comparable past rates of major depression (37% and 30%, respectively). The clinical and theoretical implications of these findings are discussed within the context of current concepts regarding the development of depressive symptoms in patients with anxiety disorders. PMID- 2327494 TI - Impact of life events on subjects with panic disorder and on comparison subjects. AB - A questionnaire measure of major life events was given to 64 subjects with diagnoses of panic disorder with agoraphobia, 33 subjects with other anxiety disorders, and 34 nonanxious subjects. Anxious subjects indicated the life events that had occurred in the 6-month period immediately before their current disorder began and rated the impact of each event on a 7-point scale. Nonanxious subjects made the same ratings for a 6-month period 1 1/2-2 years before the study. There was no significant difference between groups in the number of life events reported. However, anxious subjects rated these events as having a significantly greater negative impact than did nonanxious subjects. PMID- 2327495 TI - Convergent validity of measures of PTSD in Vietnam combat veterans. AB - The authors evaluated the convergent validity of several widely used psychometric tests of posttraumatic stress disorder (PTSD) symptoms against DSM-III-R criteria for PTSD in 130 Vietnam combat veterans. Significant positive correlations were found between these instruments and the number of DSM-III-R symptoms endorsed, supporting the validity of psychometric instruments as continuous measures of PTSD symptom severity. The various psychometric measures also correlated moderately with one another, suggesting that they assess related but somewhat separate PTSD phenomena. Finally, predicted relationships between stressors and symptoms were supported by significant correlations between degree of traumatic combat exposure and DSM-III-R and psychometric indexes of PTSD. PMID- 2327496 TI - Will we save the homeless mentally ill? AB - Progress in alleviating the plight of the homeless mentally ill has been very slow and disappointing. After reviewing the needs of the homeless mentally ill, the author makes recommendations for immediate action. Extensive case management services should be implemented rather than simply discussed. All incompetent and/or dangerous or gravely disabled homeless mentally ill persons should be brought to hospitals, involuntarily if necessary. Cost-effective alternatives to hospitals with varying degrees of structure should be provided. Involuntary mechanisms such as conservatorship and outpatient commitment should be used when needed. The emphasis should be on timely transfer to acceptable treatment and living situations rather than waiting for the ideal. PMID- 2327497 TI - Patterns of depressive symptoms in expectant and new parents. AB - Depressive symptoms were assessed in 86 couples during pregnancy and after childbirth. Although 59.3% (N = 51) of the couples contained at least one symptomatic spouse during the transition to parenthood, both spouses were symptomatic in only 11.1% (N = 4) of the affected couples during pregnancy and 12.5% (N = 4) after childbirth. PMID- 2327498 TI - Autoantibodies to brain lipids in schizophrenia. AB - Serum IgG antibody to brain lipids was measured with an ELISA technique in 38 schizophrenic patients and 22 normal subjects. There were no significant differences between groups. The authors discuss methodological differences between this study and studies with positive findings. PMID- 2327499 TI - Use of extremely low doses of fluphenazine decanoate. PMID- 2327500 TI - Psychoactive abuse potential of Robitussin-DM. PMID- 2327501 TI - Psychological distress related to sexual abuse in a patient undergoing hemodialysis. PMID- 2327502 TI - Control of bed-wetting with benztropine. PMID- 2327503 TI - Persistence of psychiatric symptoms in HIV seropositive persons. PMID- 2327504 TI - Low serum albumin levels and risk of delirium. PMID- 2327505 TI - Exposure to ultraviolet B radiation during phototherapy. PMID- 2327506 TI - Diagnostic criteria for epilepsy-related mental changes. PMID- 2327507 TI - Psychiatric reaction to ketoconazole. PMID- 2327508 TI - Legitimacy of factitious disorder diagnoses. PMID- 2327509 TI - Comorbidity of psychiatric disorders in adolescents. PMID- 2327510 TI - Ensuring the normalcy of "normal" volunteers. PMID- 2327511 TI - Criticism of review of book on divorce. PMID- 2327512 TI - The declining presence of the "young American"--a demographic reality, present and future. PMID- 2327513 TI - Indirect treatment of traumatic psychological experiences: the use of TAT cards. AB - An indirect therapeutic intervention using TAT cards in the treatment of a 13 year-old boy, who had accidentally killed a younger relative seven years ago, is described. Using a dialectical approach, the cotherapists presented contrasting TAT stories in an attempt to reflect the boy's inner conflicts, ambivalencies, and distorted perceptions. This approach provided the boy with alternate and more positive ways of perceiving and dealing with reality and enable him to relate to and cope with the taboo topic of the traumatic incident in a relatively short time. It is suggested that the use of this approach in highly sensitive situations, where considerable caution is warranted, should be explored with various age groups. PMID- 2327514 TI - Towards breaking the cycle of intergenerational abuse. AB - A quantitative single case study of an adolescent mother with a history of being abused as a child is presented. It illustrates the diagnostic and treatment issues during an intervention designed to break the cycle of intergenerational abuse. Drawing upon an ecological, transactional model of development, the case study utilized a multimethod, longitudinal approach to assess the mother's history and current psychosocial functioning, the infant's developmental competence and attachment status, patterns of mother-infant interaction and components of the family's social ecology. Measures were administered during a baseline period and systematically repeated throughout the one-year period of intervention. The treatment involved two weekly therapy sessions; one, an individual session for the mother and the other, a session in which mother and infant were seen together. The findings at the one-year evaluation showed improved maternal psychosocial functioning, the infant's shift from an insecure to a secure attachment classification and improved patterns of mother-infant interactions. The implications of this therapeutic approach and the use of single case methodology are discussed. PMID- 2327515 TI - Let the debate being: status of IVDA's with AIDS. PMID- 2327516 TI - Forensic sexology: paraphilic serial rape (biastophilia) and lust murder (erotophonophilia). AB - Forensic sexology is not synonymous with either forensic psychiatry or forensic psychology. It is a specialty in its own right, and is needed in the courtroom. Paraphilic sex offenders on trial are misrepresented as being, by their own choice, psychopathic or sociopathic deviates. They are unable to explain their paraphilic criminality to either themselves or society. In a case of serial rape and serial lust murder here presented, the contributory causes are examined and differentiated as hereditary predisposition, hormonal functioning; pathological relationships, sexual abuse; and syndrome overlap with bipolar disorder, schizoid disorder, antisocial personality disorder, epilepsy, and multiple personality. The precipitating causes were differentiated as childhood head injuries, and adult head injury at age 20. Left impact trauma and sexological trauma were sequelae of the adult injury. The full range of diagnostic resources was not available for a prisoner on death row. Capital punishment has not prevented the reemergence in each new generation of serial rape and serial lust murder as an epidemiological, public health problem. Punishment is an ineffectual substitute for epidemiological research into cause, effect, and prevention. PMID- 2327517 TI - The importance of balance in the practice of psychotherapy. AB - Specialization is inviting because it can lead most directly to original work, recognition, and success. However, it can also result in narrow experience and outlook, which represent disabilities in any work, but all the more so in the practice of psychotherapy, where our major task is to understand and help people with their feelings and their lives. Constricted, bored psychotherapists are hampered in the extent to which they can be useful to people in difficulty, especially since a major portion of psychotherapeutic help must come through a vital, authentic relationship between two real people. Psychotherapists who are educators should encourage their students and residents to early adopt attitudes that will lead to broader rather than narrower approaches to their psychotherapeutic work. In so doing, they will enable future therapists to enjoy for many years the creative and stimulating rewards of the balanced practice of psychotherapy. PMID- 2327518 TI - Older psychiatrists and their psychotherapy practice. AB - Interviews with 15 elderly practicing psychiatrists found them cheerful, optimistic and enjoying doing psychotherapy. Most practiced as they had been trained originally, saw outpatients primarily--though fewer and less frequently- than they had earlier in their careers. They experienced fewer transference and countertransference difficulties; and were neither more advice-giving nor self disclosing than earlier in their careers. All had suffered numerous traumatic events, including ill health and death of spouses, but managed to keep that information out of the therapeutic relationship. Their primary professional concern was maintaining their practices; their major personal concern was the possibility of disability. PMID- 2327519 TI - Regressive transferences--a manifestation of primitive personality organization. AB - Regressive transferences are but one manifestation of dynamic infantile and frequently unconscious fantasies seen in patients with a primitive personality organization. Such transference relationships may vary from an apparent profound unrelatedness to intense symbiotic dependencies. These transferences are primarily preoedipal and may include grandiose, persecuting, somatizing and dehumanized object experiences as well as narcissistic idealizing and denigrating selfobject formations. Three types of regressive transferences in patients with primitive personalities are described: primitive libidinal, transference automatism, and somatization. All three demonstrate symbolically meaningful but primarily unconscious primitive transference reenactments. Regressive transferences not only represent impulses seeking gratification but are also restitutive attempts for earlier losses and lack of self-cohesion. Patients with a primitive personality organization often have suffered early deprivations that bring about the formation of unstable internal representations. This makes acceptance of ambivalence and mourning difficult due to fear of ego dissolution caused by the aggression toward the self and others. Identification and exploration of shared intersubjective phenomena may facilitate conscious reconstruction and eventual interpretation of these regressive transferences. PMID- 2327520 TI - Exploring the meanings of substance abuse: an important dimension of early work with borderline patients. AB - In this paper we encourage the evaluating clinician to approach substance abuse as though it were a symptom, like any other, that serves a psychological function for the borderline individual. During the assessment phase, this approach is likely to (1) generate interest among treaters (2) solidify rapport with the patient resulting in a positive attitude toward the assessing clinician with more informative self-reports, (3) elucidate, for the clinician, the patient's major deficits in personality structure, especially the inability to understand and control affective states, and (4) stimulate the patient's curiosity about the way in which emotions are perceived and processed. PMID- 2327521 TI - Common psychological defenses seen in the treatment of sexually abused adolescents. AB - The negative psychological aftermath of sexual abuse is complex and has a direct correlation with the establishment of maladaptive defense mechanisms. Long-term psychotherapy can allow the adolescent patient to establish the cognitive and affective connections to the original trauma and work through the residue of guilt and shame. As mastery is achieved through the treatment process, higher level defenses should become more pronounced. Because the repressed memories related to the sexual trauma need to be unfolded slowly, so that the defensive capacities are not overwhelmed, treatment may need to be continued into adulthood. This paper proposes a theoretical discussion to assess the psychological defenses commonly seen in adolescents with a history of sexual abuse. Further research is needed on the sexually abused patient's intrapsychic experience and the development of defenses used to ward off painful memories related to the sexual trauma. PMID- 2327522 TI - Transformations in self-understanding in surgeons whose treatment efforts were not successful. AB - This study, dealing with cardiac and cancer surgeons' reactions to treatment failure (i.e., situations where surgeons despite their best efforts were unable to successfully treat their patients) found changes in the surgeons that bore striking resemblance to certain changes in people undergoing psychotherapy. Twenty surgeons participated. Each reported on two of his patients, all of whom had undergone surgery that failed to stem the progress of their disease. The life expectancy of these patients was approximately one year. Each surgeon saw one of his patients only until completion of the customary postoperative care and then referred him/her back to the original physician. The other patient was seen by the surgeon on a once-monthly basis even after postoperative care had been completed. While the surgeons had decided to be part of the study "for the possible good of the patients," many reported experiences of transformations in their own self-understanding. The particular elements of healing and self understanding included a sense of self-forgiveness and acceptance, a strengthened feeling of human connectedness, an enhanced sense of meaning about what they were doing, and a sense of openness and hope for the future. Perhaps this self transformative process and the possible mechanisms for change discussed mimic what happens in psychotherapy patients. PMID- 2327523 TI - Referral issues in psychotherapy and psychoanalysis. AB - The authors consider the complex decisions involved in the initial consultation of a person looking for treatment when this person must be referred to a professional colleague. They explore the way decisions are made in the referral processes and the complex practical and transference-countertransference issues that arise at the outset and whenever second opinions are sought during an ongoing psychotherapy. They present four clinical examples in varying detail to emphasize how readily misunderstandings can develop when even experienced consultants are not sufficiently alert to the complex conscious and unconscious motives and messages being expressed in the exchanges. They make recommendations on how to conceptualize and respond to them. PMID- 2327524 TI - The emergence of psychopathology in a previously adaptive mother-infant dyad. AB - A mother and her six-week-old infant began attending group therapy sessions designed to raise awareness of developmental events. The mother consistently displayed a high degree of responsiveness and sensitivity to the infant's needs; in fact, her behavior served as a model of adaptive interaction for the entire group. After six months of sessions, when the infant manifested full-blown weaning patterns, the mother reported symptoms indicating a major depressive episode, such as pervasive dejection and rejection, listlessness, and anxiety attacks. After several individual sessions, during which discussion focused on the etiology of these emotions, the depression remitted and the mother was able to resume previous adaptive interaction designed to promote the infant's development. This case study reveals that highly adaptive parents may be susceptible to depression when developmental events that signify imminent separation from their infants or a similar dramatic change in their relationship occur. PMID- 2327525 TI - Quality assurance and computer-based patient records. PMID- 2327526 TI - Tobacco taxation as health policy in the Third World. PMID- 2327527 TI - Improving influenza vaccination performance in an HMO setting: the use of computer-generated reminders and peer comparison feedback. AB - We evaluated a program for improving influenza immunization performance in a health maintenance organization (HMO). The HMO implemented several interventions successively from 1984-87: a postcard reminder to members at high risk for complications of influenza, a computer-generated reminder to the physician at the time of any primary care visit by high-risk patients, performance feedback to chiefs of service, and, finally, retrospective feedback to each physician comparing his/her performance with that of the other physicians. We examined immunization rates for a group of members older than age 65, a high-risk group under age 65, and a group of diabetic members who had not been subject to the reminders (vs a group who had been covered by the program). Vaccination rates were increased in those diabetic members who received reminders. Nevertheless, among members younger and older than age 65 whose experience was observed over three flu seasons, a significant increase in vaccination rates was not achieved until physician feedback was added to the program. We conclude that each element of the reminder and feedback program has contributed to the overall increase in vaccination rates at the HMO and that effective ongoing influenza immunization programs can be implemented in practice settings with appropriate systems support. PMID- 2327528 TI - Tobacco excise and declining tobacco consumption: the case of Papua New Guinea. AB - Excise elasticities of demand for non-cigarette tobacco and cigarettes were calculated for Papua New Guinea for the 14 years 1973-86. Respectively, these were -0.50 and -0.71. This means that 10 percent increases in cigarette and non cigarette tobacco excise are associated with an estimated 7.1 percent fall in demand for cigarettes and a 5 percent decrease in the demand for tobacco. As tax (excise) elasticities would normally be significantly smaller than price elasticities, these results imply that the consumption of cigarettes and tobacco in Papua New Guinea are more responsive to prices than in the United States and other Western countries. The level of excise is therefore an important and practical instrument for the control of consumption. These elasticities appear to be the first reported for a developing country. It is suggested that if they are indicative of consumer behavior in lower income countries then increasing tobacco and cigarette excise should be considered as an important strategy for the control of smoking in these countries which, because of their large populations, are huge markets for tobacco products and thus major targets for tobacco control measures. PMID- 2327529 TI - Smoking before, during, and after pregnancy. AB - We report the first national data on smoking before, during, and after pregnancy. Estimates are based on the 1986 Linked Telephone Survey that reinterviewed 1,550 White women 20-44 years of age who were respondents to the 1985 National Health Interview Survey. An estimated 39 percent of White women who had smoked before pregnancy quit smoking while pregnant (27 percent when they found out they were pregnant and 12 percent later during pregnancy). Women with less than 12 years of education were five times as likely to smoke and one-fourth as likely to quit as those with 16 or more years of education. Women who smoked more than one pack of cigarettes per day before pregnancy were one-fifth as likely to quit as those smoking less. Of the women who quit, 70 percent resumed smoking within one year of delivery. Of those who relapsed, 67 percent resumed smoking within three months of delivery and 93 percent within six months. There is little evidence of educational differentials in relapse rates. The fact that relapse remains high suggests that while health of the fetus is a strong influence on women's smoking habits, women may be less aware of the effect of passive smoke on the infant. PMID- 2327530 TI - Information on tar and nicotine yields on cigarette packages. AB - We examined information on tar and nicotine yields on the packages of 160 cigarette brands, 58 percent of the 275 brands for which tar and nicotine yields were listed in a recent Federal Trade Commission report. The tar yield was indicated on 14 percent, the nicotine yield was indicated on 11 percent. As tar yield increased among brands, the yield was progressively less likely to be shown on the package and was not disclosed on the package of any cigarette yielding 11 mg or more of tar. PMID- 2327531 TI - Comparative evaluation of American Cancer Society and American Lung Association smoking cessation clinics. AB - We compared the effectiveness of American Cancer Society, FreshStart, American Lung Association, Freedom from Smoking, and laboratory clinic methods in subjects (N = 1041) from three communities. Three-month follow-up results favored the laboratory method over the two public service approaches on both a prevalence and a sustained abstinence measure. At one-year follow-up, treatment effects for smoking prevalence were no longer significant. However, sustained abstinence results at one-year remained highly significant and favored the more intensive laboratory and Freedom from Smoking clinics over the FreshStart method. FreshStart fared less well than the other interventions both in producing initial quit attempts and in sustaining abstinence among initial quitters. It should be noted, however, that FreshStart requires considerably less facilitator contact than do the other approaches. Unexpected outcome effects occurred for treatment location. Future clinic programs should include a specific target date for quitting and should place more emphasis upon recycling participants who fail to sustain abstinence. PMID- 2327532 TI - Benzene, benzo(a)pyrene, and lead in smoke from tobacco products other than cigarettes. AB - Benzene, benzo(a)pyrene (BaP), and lead in mainstream smoke from cigars, roll your-own (RYO) cigarette and pipe tobaccos were sampled to evaluate their potential health significance. Results with reference cigarettes were consistent with published values, providing support for the methodology employed. The emissions of benzene and BaP, expressed as mass emitted per gram of tobacco consumed, were similar for all products evaluated; for benzene, the mean values for cigars, RYO cigarette and pipe tobaccos were 156 +/- 52, 68 +/- 11, and 242 +/- 126 micrograms/g, respectively. Mean values for BaP were 42 +/- 7 and 48 +/- 4 ng/g for cigars and RYO cigarette tobacco, respectively. Lead values were below the limit of reliable quantitation in all cases. The mean benzene concentrations in a puff ranged from 1 to 2 x 10(5) micrograms/m3 for cigars, RYO cigarette and pipe tobaccos. For BaP, the puff concentration averaged about 60 micrograms/m3 for cigars and RYO cigarette tobacco. The results suggest that smoking cigars, pipes or RYO cigarettes leads to potential exposures which exceed the No Significant Risk levels of benzene and BaP set pursuant to California's Proposition 65. These tobacco products are now required to bear a health hazard warning when sold in California. We recommend that this be adopted as national policy. PMID- 2327533 TI - Long-term effectiveness of mass media led antismoking campaigns in Australia. AB - A community antismoking campaign began in Sydney, Australia in 1983, and in Melbourne in 1984. These campaigns purchased prime-time television advertising spots to set the community agenda. An intense effort was made to ensure that antismoking activities were maximized at the school, organizational, and community level. Smoking prevalences in both cities from 1981 were fitted with a statistical model to identify any underlying trend, to assess any immediate impact, and to assess the longer term effect of continuing to conduct such campaigns, i.e. to identify any change in the underlying trend. During the years before the antismoking campaigns, there was no observable trend in smoking prevalence in either city. At the beginning of the campaigns, there was an immediate drop of more than two percentage points in male and female smoking prevalence in both cities. Thereafter, a decline of about 1.5 percentage points per year was observed among males. No post campaign trend was observed in smoking prevalence for women in either city. These data support conducting coordinated community campaigns to reduce current smoking prevalence. PMID- 2327534 TI - A twin study of the effects of the Vietnam conflict on alcohol drinking patterns. AB - This study examines the association between military service in Southeast Asia and alcohol drinking patterns in 2,169 male-male monozygotic twin pairs who both served on active military duty during the Vietnam era (1965-75). Data on alcohol drinking were collected in 1987 by mail and telephone interview. The alcohol drinking measures include three indicators of abstention (lifetime abstainer, lifetime non-regular drinker, and current abstainer) and two indicators of consumption (average daily ethanol consumption and high consumption). In unadjusted and co-twin adjusted analyses, neither service in Southeast Asia nor combat exposure was significantly associated with any measure of abstention. In the co-twin adjusted analysis, there was no association of Southeast Asia service and combat exposure with average daily ethanol consumption. After adjustment for co-twin effects, 4.0 percent of non-Southeast Asia veterans were high consumers compared to 6.7 percent of Southeast Asia veterans who served in high combat. We conclude that prior military service in a war zone has a relatively modest long term effect on the alcohol drinking patterns of male veterans. PMID- 2327535 TI - Violence during pregnancy and substance use. AB - Violent incidents were assessed as part of a prospective study of 1,243 pregnant women. Participants were predominantly poor, urban, minority group women. Seven percent (n = 92) of women reported physical or sexual violence during pregnancy. Most of the women (94 percent) knew their assailant. Victims of violence were at greater risk of having a history of depression and attempted suicide, having more current depressive symptoms, reporting less happiness about being pregnant, and receiving less emotional support from others for the current pregnancy. Comparisons of victims and non-victims showed that victims were more likely to be users of alcohol and drugs. In addition, partners of victims were more likely to use marijuana and cocaine. When possible confounders were controlled using multivariable analyses, a woman's alcohol use during pregnancy and her partner's drug use were independently associated with an increased risk of being a victim of violence during pregnancy. Results of this study highlight the importance of assessing exposure to violence during prenatal care, especially among women who are heavy users of alcohol or drugs or whose partners use these substances. PMID- 2327537 TI - HIV antibody testing among adults in the United States: data from 1988 NHIS. AB - Data collected from 21,168 adults using the 1988 AIDS supplement to the National Health Interview Survey were examined to determine awareness of and experience with HIV antibody testing in the United States. Three-fourths of adults knew of the blood test for HIV antibodies; awareness was lower among Blacks, Hispanics, older adults, and those less educated. Overall, 17 percent of adults had been tested; of these, 73 percent because of blood donation, 14 percent through other non-voluntary programs (such as military induction), and 16 percent sought testing voluntarily. While a smaller proportion of Black and Hispanic adults had been tested, they were more likely than their White non-Hispanic counterparts to have been tested voluntarily. Persons who reported belonging to groups with high risk behaviors were also more likely to have been voluntarily tested. Most of those tested voluntarily received their test results, but only one-third also received prevention information. Three percent of adults plan to be tested voluntarily in the next year; about half will seek testing through their doctor or health maintenance organization. PMID- 2327536 TI - Risk factors for depressive symptomatology in a drug using population. AB - This study employs a prospective design to examine possible personality, drug use, stressful life event, and social support-related variables associated with the onset of a depressive episode in a cohort of psychoactive drug using young adults. Two waves of data, collected one year apart, were available on 942 individuals. Cases (n = 62) were free of depressive symptoms at time 1 but reported significant symptomatology at time 2 as measured by the depression subscale of the Brief Symptom Inventory. Controls (n = 490) were those free of depressive symptoms at both time points. In multivariate analyses, users of the central nervous system depressant methaqualone had a nearly four-fold elevated risk for depressed mood as compared to nonusers. Additional risk factors significant after multivariate adjustment included lower self-esteem at time 1 and negative life events. These results highlight the multifactorial nature of depressive symptomatology. PMID- 2327538 TI - Carbon monoxide in indoor ice skating rinks: evaluation of absorption by adult hockey players. AB - We evaluated alveolar carbon monoxide (CO) levels of 122 male, adult hockey players active in recreational leagues of the Quebec City region (Canada), before and after 10 weekly 90-minute games in 10 different rinks. We also determined exposure by quantifying the average CO level in the rink during the games. Other variables documented included age, pulmonary function, aerobic capacity, and smoking status. Environmental concentrations varied from 1.6 to 131.5 parts per million (ppm). We examined the absorption/exposure relationship using a simple linear regression model. In low CO exposure levels, physical exercise lowered the alveolar CO concentration. However, we noted that for each 10 ppm of CO in the ambient air, the players had adsorbed enough CO to raise their carboxyhemoglobin (COHb) levels by 1 percent. This relationship was true both for smokers and non smokers. We suggest that an average environmental concentration of 20 ppm of CO for the duration of a hockey game (90 minutes) should be reference limit not to be exceeded in indoor skating rinks. PMID- 2327540 TI - Smoking and consistently high use of medical care among older HMO members. AB - Smoking behavior of consistently high and low users of medical care services were compared in two groups of older health maintenance organization (HMO) members continuously enrolled for five years and a subgroup who were continuously enrolled for 10 years. Smokers and former smokers, combined, were more likely than never-smokers to be consistently high users of ambulatory services (52 percent vs 34 percent in the five-year group, and 45 percent vs 30 percent in the 10-year group). PMID- 2327539 TI - Passive smoking and 20-year cardiovascular disease mortality among nonsmoking wives, Evans County, Georgia. AB - The association of passive smoking and cardiovascular disease (CVD) mortality was assessed in a cohort of 513 rural, married Black and White women who were disease free and self-described as never-smokers at baseline in 1960. Over a 20-year period, 76 of 147 total deaths were attributed to CVD. Relative risk estimates adjusted for age, cholesterol, blood pressure, and body mass from proportional hazards models were 1.59 for CVD (95% CI = 0.99, 2.57) and 1.39 (CI = 0.99, 1.94) for all cause mortality among women with husbands who smoked cigarettes. PMID- 2327541 TI - Routine communication in sexually transmitted disease clinics: an observational study. AB - Sixty STD patients were followed during the course of their clinic visit which averaged 2.75 professional contacts. Based on audiotape analysis, virtually all patients received a diagnosis; however, 25 percent of the patients did not receive any information about treatment or prevention, and only 57 percent of patients were given complete information. Patient recall of the information they were given averaged about 43 percent. Patients not seen by a physician during their clinic visit achieved higher recall rates than patients seen by a physician. PMID- 2327542 TI - Increase in condom sales following AIDS education and publicity, United States. AB - Data from a national probability sample of drug stores show that condom sales rose from 240 million annually in 1986 to 299 million in 1988. The greatest increase occurred in 1987 after the Surgeon General's report on AIDS was released. Sales of latex condoms with spermicide rose 116 percent. Sales of other types of condoms increased less. These data suggest that Americans are using more condoms and probably more effective condoms in response to AIDS education. PMID- 2327543 TI - Car design and risk of pedestrian deaths. AB - Fatal pedestrian injury rates by cars with relatively sharp front-corner designs were compared to such rates by cars of similar-size with relatively smooth front corner designs. The relative risk of death by front-corner impact was 26 percent greater among the sharp-cornered cars. Pedestrian death rates from impact with other points on the cars and insurance claim frequencies among the studied cars were similar between the two sets of cars. PMID- 2327544 TI - Males' use of public health department family planning services. AB - Information was obtained from over 200 males visiting a family planning service either to obtain free-of-charge condoms or incidental to accompanying their female partner. The former group was younger and more likely to reside near the health department: over 40 percent of this group used the health department as sole condom source. Both groups indicated willingness to share in costs for male services. Future programs need to more effectively plan public health family planning for these males. PMID- 2327545 TI - Young children who drown in hot tubs, spas, and whirlpools in California: a 26 year survey. AB - A survey of drownings in hot tubs, spas, and whirlpools in California 1960-85 suggests a person- and site-specific profile. The identified 74 deaths occurred mostly in White children, under two years of age, in Southern California, during the late afternoons, from May through August. From 1967 to 1985, the drowning rate increased tenfold. The deaths were associated with access to the water, lack of supervision, neuromotor handicaps, and entrapment by suction. Educational and environmental control efforts are required to reduce the incidence. PMID- 2327546 TI - AIDS prevention for i.v. drug users and their sexual partners in Philadelphia. PMID- 2327547 TI - Vermont International Travel Clinic: group or individual appointments. PMID- 2327548 TI - Letters on epidemiologic research methods. PMID- 2327549 TI - Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases. AB - We present the results of a clinicopathologic study of 109 patients with endometrial stromal sarcoma and eight patients with endometrial stromal nodule. Of the 109 patients with endometrial stromal sarcoma, follow-up was obtained on 93 (85%). The stage distribution of the patients with stromal sarcoma and the number of patients with follow-up (numerator) compared to the total number of patients in each stage (denominator) are: Stage 1, 73/85; Stage II, 3/6; Stage III, 11/11; Stage IV, 6/7. Stage II patients are considered separately in the analysis. Thirty-six percent of the Stage I patients experienced one or more relapses. Of these, six (23%) died of disease from 11 to 360 months from diagnosis (median, 79 months). Nine (35%) were alive with disease. Of the eleven Stage III patients, eight had one or more relapses and of these, six died of disease. Of the six Stage IV patients, five had one or more relapses and of these, three died of disease. The outcome differences between Stages I, III, and IV are statistically significant (p less than .01). Microscopic features evaluated included the mitotic index (MI = number of mitoses/10 high-power fields) and cytologic atypia. Forty-five percent of Stage I patients who had both rare mitotic figures and minimal atypia had one or more relapses and of these, two (13%) died of disease at 85 and 360 months, respectively. Thus, neither MI nor cytologic atypia were predictive of tumor recurrence for patients with Stage I tumors. PMID- 2327550 TI - Stromal endometriosis of the uterine cervix. A variant of endometriosis that may simulate a sarcoma. AB - Six cases of endometriosis of the uterine cervix characterized by the exclusive or almost exclusive presence of endometriotic stroma are reported. These cases of "stromal endometriosis" were encountered in women 29 to 64 (mean, 43) years of age. Three of them presented with abnormal bleeding, one presented with weight loss and abdominal swelling due to an ovarian clear cell adenocarcinoma, and two were asymptomatic. None of the patients had a history of pelvic endometriosis. In three cases, red lesions of the ectocervical mucosa were recognized on pelvic examination. Histological examination of the lesions showed well circumscribed foci within the superficial stroma of the cervix that were composed of an admixture of closely packed cells resembling endometrial stromal cells, small blood vessels, and extravasated erythrocytes. Endometrial-type glands were absent in the initial sections in all of the cases, but rare glands were found in deeper sections in one case. Apart from the absence or paucity of endometrial glands, the clinical and pathological features of the lesions were similar to those of previously described cases of superficial endometriosis of the cervix. Because of the pure or almost pure stromal composition of the lesion, however, it can be confused histologically with benign and malignant neoplasms, particularly low grade endometrial stromal sarcoma and Kaposi's sarcoma. PMID- 2327551 TI - Primary malignant lymphoma arising in postmastectomy lymphedema. Another facet of the Stewart-Treves syndrome. AB - In rare cases, primary malignant lymphomas may arise in the soft tissues. Only one previous case has arisen in the context of chronic lymphedema. Because of the clinical appearance of such lesions, which resemble violaceous nodular or plaquelike tumors, they may be confused clinically with lymphedema-associated angiosarcomas occurring after radical mastectomy (Stewart-Treves syndrome). Furthermore, the histologic appearance of some lymphomas and angiosarcomas may also be similar. We studied two women with primary postmastectomy lymphedema related malignant lymphoma in the soft tissues of the upper arm. These tumors arose 11 and 30 years, respectively, after radical removal of ductal mammary carcinomas. Histologically, one neoplasm mimicked metastatic carcinoma or epithelioid angiosarcoma; whereas the other was initially confused with a variety of pathologic entities, including vasculitis, epithelioid hemangioma, and malignant fibrous histiocytoma. The lymphoid nature of both lesions was confirmed by immunoreactivity for leukocyte common antigen in addition to the B-lymphocyte marker, L26. Conversely, vascular and epithelial determinants were absent. One patient's disease pursued an indolent course; she died of unknown causes but with no evidence of lymphoma at last follow-up. The second patient is currently in remission on chemotherapy. Awareness of the existence of lymphedema-related malignant lymphoma and familiarity with methods used for its distinction from epithelioid vascular sarcomas should prevent unnecessary surgery. PMID- 2327552 TI - Consultation case. Differentiating rhabdomyoblastoma. PMID- 2327553 TI - Adrenal cortical adenoma in the spinal canal of an 8-year-old girl. AB - An ectopic adrenal cortical adenoma containing high levels of androstenedione but without clinically detectable virilizing effects was found in the spinal intradural space of an 8-year-old girl. The tumor, which was located at the L2 level, manifested itself clinically by a short history of bilateral leg pain. It was well encapsulated; therefore, total surgical removal was accomplished. The light microscopic appearance of the tumor was typical of adenomatous adrenal cortical tissue. Ultrastructurally, it also showed characteristic features of steroid-producing tumors, including very abundant smooth endoplasmic reticulum and giant mitochondria with tubulovesicular and circular cristae. Frozen tissue analyzed by radioimmunoassay was found to contain almost 20 times the normal tissue level of androstenedione. There was no elevation of cortisol or aldosterone levels in the tumor. Postoperative magnetic resonance imaging (MRI) scan of the retroperitoneum showed no abnormalities in the patient's adrenal glands. Serum androstenedione levels were normal. We postulate that the adenoma developed from congenital ectopic rests of intraspinal adrenal tissue. Although ectopic occurrence of adrenal cortical tissue has been recorded in other areas, neither such rests nor tumors developing from them have been previously reported within the spinal canal. PMID- 2327554 TI - Crohn's dysplasia. PMID- 2327555 TI - Transplantation of the small intestine: the pathologist's perspective. AB - Small-bowel transplantation is now ready for clinical trials. The surgical techniques and methods for immunosuppression and monitoring bowel status have been developed in animal models over the past 30 years. Several attempts at small bowel transplantation in humans have already been reported. In the course of future trials, pathologists will be involved in the monitoring of the posttransplant course by mucosal biopsies and functional studies, including maltose and xylose absorption tests. The morphology of rejection has been studied in canine and rat models. Activated lymphocytes and plasma cells infiltrate the lamina propria and invade crypt epithelium, causing "cryptitis." Villous blunting ensues, resulting eventually in necrosis. Graft survival without immunosuppression is about 10 days. Under Cyclosporine immunosuppression, a lymphoplasmacytic infiltrate has been noted around nerves and vessels in the submucosa. The overlying mucosa may be relatively normal. End-stage bowel is characterized by a contracted, scarred mass. Due to the large amount of lymphoid tissue in the allograft, graft-versus-host disease is a significant problem in small-bowel transplantation. PMID- 2327556 TI - ELISA inhibition method in detection of mite and chironomid antigens in environmental samples of dust, soil and air. AB - To determine the amount of chironomids and mite antigens in the indoor and outdoor environment, we investigated samples from air, soil and house dust in the area around Lake Kojima, located in the western part of Japan. Three species of chironomid (Tokunagayusurika akamusi, Chironomus yoshimatsui and Chironomus plumosus) and species of mite, Dermatophagoides farinae antigens were studied. The antigens were detected and quantified by inhibition ELISA. In the outdoor environment, C. yoshimatsui and T. akamusi antigens were more abundant than mite antigen, and seasonal fluctuations were observed. In the indoor environment, mite was the predominant antigen. D. farinae antigen was detected in almost all dust samples, with a slight reduction in winter compared to summer. PMID- 2327557 TI - Enhancement of basophil histamine release by a human basophil-like cell promoting activity. AB - A basophil-like cell promoting activity (BaPA) is a lymphokine which has the ability to proliferate metachromatically staining cells in human bone marrow. We studied the effect of BaPA on histamine release from human peripheral basophils. BaPA did not directly induce histamine release from basophils. However BaPA ranging from 0.001 to 0.5 U/ml enhanced histamine release from basophils stimulated with anti-IgE, calcium ionophore A23187 or FMLP in a dose-dependent manner. On the basis of recent observations that in addition to their capacity for proliferating progenitor cells, colony-stimulating factors are capable of regulating functions of end-stage cells of the same lineage, this finding that BaPA is able to modulate a basophil function raises the possibility that BaPA also regulates progenitors of basophils. PMID- 2327558 TI - Value of immunologic tests in cow milk allergy. AB - The aim of this study has been to clarify the immunopathogenesis and diagnosis of cow milk allergy (CMA). Thirty-four children with symptoms suggestive of CMA had a challenge test with cow milk (CM) and an estimation of their immunological response. Nineteen of the 34 children reacted to CM challenge test. We measured serum levels of immunoglobulins G, A, M and E, complement fractions 3 and 4, class specific CM antibodies as well as the numbers of the different lymphocyte subsets and the responses of lymphocytes in whole blood to stimulation by phytohemagglutinin (PHA), concanavalin A (ConA) and beta-lactoglobulin (BLG). Twelve (63%) of the children who reacted had high levels of IgE CM-specific antibodies; they had lower mean levels of serum IgA and lower lymphocyte stimulation indices with BLG and PHA than the rest of the children (37%) who reacted on CM, but were without IgE antibodies. Of these seven children, five gave elevated responses to stimulation with BLG, and in three of six the helper/suppressor lymphocyte ratio rose during the challenge test. Most (10) of 15 children who showed no reaction when challenged with CM at hospital, had earlier had cutaneous symptoms closely related to CM formula feeding. No single laboratory method was sufficient to discriminate between the children who reacted to CM and those who did not. The best combination of tests was measurements of CM specific IgE and the index of lymphocyte stimulation with BLG. This combination had a sensitivity of 88% and specificity of 67% for predicting a clinical reaction. PMID- 2327559 TI - Heterozygous alpha 1-antichymotrypsin and PiZ alpha 1-antitrypsin deficiency. Prevalence and clinical spectrum in asthmatic children. AB - In a case-control study we compared the prevalence of heterozygous deficiency of two closely related anti-neutrophil protease inhibitors, alpha 1-antitrypsin and alpha 1-antichymotrypsin, in 172 consecutive children with asthma. In a cohort study the clinical spectrum and severity were compared. On the basis of family studies 5/172 (2.9%) were classified as heterozygotes for alpha 1 antichymotrypsin deficiency, a high prevalence compared with that of an unselected adult population (prevalence ratio 4.5 (1.7-11.9), P less than 0.005). This finding suggests that the carrier state of this rare allele (prevalence 0.64%) may predispose to asthma in children. Among these heterozygous patients the prevalence of positive RAST tests for foodstuffs was significantly increased (prevalence ratio 4.8 (1.7-13.2), P less than 0.005) and 2/5 manifested food allergy with Quincke oedema. Either the PiMZ or SZ phenotype of alpha 1 antitrypsin deficiency was found in 12 (7.0%) of the 172 patients, a prevalence similar to that of a normal population (prevalence ratio 1.3 (0.67-2.6), P = 0.44). However, the asthma was more severe among the Z allele carriers, judged by the number of hospital admissions, compared with the non-Z asthmatic children (mean 2.92 vs. 1.72, P less than 0.05). The results indicate that heterozygous deficiency of protease inhibitors directed against neutrophil proteases may affect the severity and clinical spectrum of childhood asthma, and to some degree be predisposing. PMID- 2327560 TI - Storage mite allergy among bakers. AB - Allergy to storage mites has been shown among farmers and grain elevator workers. This study aimed to examine whether bakers also are sensitized to storage mites. Twenty-three bakers or other employees in bakeries suffering from nasal or pulmonary symptoms were compared with 17 control persons with no relation to bakery work or agriculture. All participants underwent skin prick test with a standard panel of allergens, four types of flour and the storage mites Acarus siro, Lepidoglyphus destructor and Tyrophagus putrescentiae, RAST to storage mites and flour, and measurement of total IgE. We found no difference between the baker group and the control group in prevalence and strength of positive skin prick test or RAST to any of the three storage mite species. In the baker group positive RAST to flour was related to positive RAST to A. siro and L. destructor, but not T. putrescentiae. Almost all bakers sensitized to flour were also sensitized to storage mites (6 of 7). We suggest that if a baker become sensitized to flour he will be more prone to develop specific IgE towards storage mites too. PMID- 2327561 TI - Who will benefit from hyposensitization? Predictive parameters in house dust mite allergic asthmatics. AB - The aim of this study was to assess the ability of various data collected before treatment to predict the therapeutic benefits of hyposensitization. Thirty-one asthmatics were hyposensitized with extract from the house dust mite Dermatophagoides pteronyssinus (Dp) for 2 years, 15 comparable patients served as controls. The treatment extract was either modified by coupling to monomethoxypolyethylene glycol (mPEG) or administered in a diluent containing Al(OH)3. Improvement would be either a greater than or equal to 10-fold increase in bronchial tolerance to Dp or an overall clinical effect judged from questionnaires plus diary cards. Patients improving in bronchial Dp-sensitivity after 1 year had been more sensitive to DP pre-treatment in bronchi and in basophils, and had a lower FEV1 compared with the patients not improving (P less than 0.05). Occurrence of late-phase bronchospasm to pre-treatment Dp-challenge increased the chance of clinical improvement approximately 3-fold (P less than 0.05). A certain mite exposure seems to be a condition of an improvement in symptoms/medication. In patients improving, the median allergen concentration on mattresses was equivalent to 1,000 mites/g compared with less than 250 mites/g in patients showing no clinical improvement (P = 0.1). Information on Dp-specific IgE, IgG, IgG subclasses, Dp-sensitivity in skin, nose and eyes, age, and duration of symptoms did not permit any prediction of therapeutic effect. PMID- 2327562 TI - Diagnostic value of a glass fibre-based histamine analysis for allergy testing in children. AB - The aim of this study was to compare the diagnostic value of common allergy tests with basophil histamine release in 124 children with symptoms of asthma. The patients were evaluated by case history, skin prick test, RAST-analysis, and basophil histamine release using a glass fibre-based histamine assay to 10 common inhalant allergens. The bronchial provocation test was used as a reference of "true" IgE-mediated asthma. To compare the various diagnostic parameters each absolute test value was classified into a scoring system. The concordance between the tests varied between 85-97%. In general, the best concordance was found between basophil histamine release and RAST. Sensitivity, specificity and predictive values were calculated on the basis of 104 bronchial provocation tests. It was found that histamine release was the best single analysis, followed by RAST and prick testing. The sensitivity of RAST and histamine release was very high (1.00) for pollen and house dust mites. Histamine release showed a predictive value between 0.91 and 1.00 for pollen and house dust mites, thus indicating the possibility of omitting the bronchial provocation test. In the dander group histamine release gave the best sensitivity (0.91), however at the expense of specificity (0.64), whereas RAST and skin prick test gave a specificity of 1.00. In the mould group histamine release also showed the best diagnostic value. The combination of skin testing with histamine release or RAST was of no additional diagnostic help. It is concluded that the glass fibre-based histamine analysis, which makes routine histamine release testing possible, is a reliable diagnostic test in children. PMID- 2327563 TI - Atopy and systemic reactions to drugs. AB - To elucidate whether systemic reactions (SR) to drugs should be included in the atopic status in epidemiological studies, we compared the distribution of atopy in subjects with or without a history of SR to drugs. The studied population comprised 2067 adults, 20 to 60 years old, visiting a health care center for a check-up examination. The protocol included a questionnaire related to history of SR to drugs and a Phadiatop test which evaluates on a blood sample the presence of specific IgE against common aeroallergens. Overall, 14.7% of the study group, including 66% women, reported reliable histories of SR to drugs. The cumulative prevalence of asthma, hay fever and childhood dermatitis was higher in the SR group. By contrast, the percentage of positive Phadiatop tests was similar in subjects with or without a history of SR. Thus atopy, defined by an objective criterion, i.e. the presence of specific IgE against common aero-allergens, is not associated with the occurrence of SR to drugs. Such a history should not be included as part of the atopic status. PMID- 2327564 TI - Automated assays for superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. AB - Automated assays for catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase are presented. The assay for catalase is based on the peroxidatic activity of the enzyme. The glutathione peroxidase and reductase assays measure the consumption of NADPH following the reduction of t-butyl hydroperoxide and oxidized glutathione, respectively. The assay for superoxide dismutase is based on the reduction of cytochrome c. All assays utilize the Cobas FARA clinical automated analyzer and provide considerable time savings over the manual assays. PMID- 2327565 TI - Analysis of oligogalacturonic acids with 50 or fewer residues by high-performance anion-exchange chromatography and pulsed amperometric detection. AB - Underivatized oligogalacturonic acids with a degree of polymerization (DP) ranging from 2 to 50 have been separated for the first time on a high-performance CarboPac PA1 pellicular anion-exchange stationary phase column. Baseline separation of these pectic fragments was accomplished using a nonlinear gradient of pH 6 potassium oxalate buffer as the mobile phase. Acetate buffer linear gradients were also useful as mobile phases, but only for separations of oligogalacturonic acids that were soluble in this solvent (DP less than 20). Additionally, oligogalacturonic acid separations were accomplished on a lower capacity AS4A stationary phase column. Triple pulse amperometric detection was selective, sensitive, and reproducible, nevertheless, oligogalacturonic acid response factors were affected by DP and compositional changes in the mobile phase. PMID- 2327566 TI - Electroblotting of double-stranded DNA for hybridization experiments: DNA transfer is complete within 10 minutes after pulsed-field gel electrophoresis. AB - A rapid, simple, and efficient method for DNA blotting is presented. This method is characteristic in that DNA is transferred without denaturation from an electrophoretic gel to a membrane in low-salt concentrations and denatured on the membrane after blotting. More than 89% of double-stranded DNAs ranging in size from 75 to 1.9 million bp can simultaneously be transferred from the gel to a positively charged nylon membrane within 10 min. The present "low-salt electroblotting" method is superior to other blotting methods in that it saves time and labor and its high and even transfer efficiency makes it useful for hybridization analysis. PMID- 2327567 TI - Determination of methylguanidine in plasma and urine by high-performance liquid chromatography with fluorescence detection following postcolumn derivatization. AB - A high-performance liquid chromatographic method was developed for the determination of methylguanidine in biological fluids. Methylguanidine and the internal standard were isolated from plasma by cation-exchange solid-phase extraction prior to chromatographic analysis. Urine samples were diluted and injected directly onto the analytical column. Chromatographic separation was carried out on an Ultrasil cation-exchange column using a mixture of methanol and monochloroacetate (15/85, v/v) as the mobile phase. Postcolumn derivatization of methylguanidine was carried out using alkaline ninhydrin reagent and the resulting fluorescent product was detected on-line. The method was specific, sensitive, reproducible, and linear over a wide a range of concentrations. The lower limit of detection for methylguanidine in plasma and urine was 1 and 100 ng/ml, respectively. The method was successfully employed for quantification of the levels of methylguanidine in normal and uremic human subjects, normal dogs, and dogs with ischemic-induced acute or spontaneous chronic renal failure. PMID- 2327568 TI - Arylalkylamine (serotonin) N-acetyltransferase assay using high-performance liquid chromatography with fluorescence or electrochemical detection of N acetyltryptamine. AB - A sensitive, rapid, and economical method has been developed for determination of serotonin N-acetyltransferase activity from a variety of enzyme sources. The assay is based upon separation and detection of N-acetyltryptamine formed from tryptamine and acetyl coenzyme A, by means of high-performance liquid chromatography with either electrochemical or fluorometric detection. The limit of sensitivity with both detection methods is less than 20 pmol of N acetyltryptamine formed per sample. A method for synthesis of N-acetyltryptamine, used as an external standard in the assay, is described. PMID- 2327569 TI - Separation of oligosaccharides by capillary supercritical fluid chromatography and analysis by direct coupling to high-resolution mass spectrometer: application to analysis of oligomannosidic N-glycans. AB - Supercritical fluid chromatography separations and supercritical fluid chromatography chemical ionization mass spectrometry analysis of permethylated and pertrimethylsilylated oligosaccharides are reported. Supercritical fluid chromatography was carried out using a DB-5 coated capillary column with carbon dioxide as a mobile phase. Peralkylated oligosaccharides were detected by flame ionization and by chemical ionization mass spectrometry using the GC interface. Analysis of permethylated malto-oligosaccharides, as well as oligomannosides from mannosidosis, was achieved by chemical ionization mass spectrometry with ammonia and provided the pseudo-molecular ions (M+H)+ and (M+NH4)+, in addition to some other fragments which allow interpretations of the structure of different oligosaccharides. The good resolution and sensitivity obtained emphasize the potential of supercritical fluid chromatography mass spectrometry for rapid separations and analysis of complex glycan mixtures. PMID- 2327570 TI - Sample processing alters glutathione and cysteine values in blood. AB - The accurate assessment of glutathione status of blood is essential for its use as an index of health and aging. A major variable in glutathione analysis is sample processing, and identification of optimal standard conditions is needed. Thus our objective was to evaluate several methods to determine which one yields maximal levels of free and bound glutathione and cyst(e)ine in blood. Reduced glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), and cystine were analyzed specifically by an HPLC-dual electrochemical method. The highest GSH levels were found in ultrafiltrates of hemolysates, which were 58% greater than those in acid extracts of whole blood, and accounted for 96% of the free and bound GSH in borohydride-reduced samples; GSSG was undetected. The next highest values were in acid extracts of hemolysates which were 13% greater than in extracts of whole blood; both extracts contained GSH and GSSG. Their GSSG contents expressed in GSH equivalents comprised 7-9% of GSH + GSSG. Cys levels were highest in ultrafiltrates which were 11-fold greater than in acid extracts of whole blood, accounting for 62% of the total cyst(e)ine pool. In summary, the results indicate that ultrafiltration of hemolysates is the blood processing method of choice to obtain maximal values of free and bound GSH and cyst(e)ine. PMID- 2327571 TI - Use of nonlinear regression to analyze enzyme kinetic data: application to situations of substrate contamination and background subtraction. AB - In a recent publication, A. Lundin, P. Arner, and J. Hellmer [Anal. Biochem. 177, 125-131 (1989)] describe a method whereby kinetic substrate assays can be performed when the assay mixture includes a significant contaminating levels of substrate. Their method requires various rearrangements of the data, and involves three separate linear regression calculations. We show how the same data may be analyzed directly, and far more simply, by nonlinear regression. Unlike the linear regression method, nonlinear regression allows direct calculation of the actual values for Km, Vmax, and the concentration of contaminating substrate (as well as estimates of their standard errors); the former method gives only apparent values. The nonlinear regression technique is also statistically a more valid means of analysis, as the rearrangements required to give linearized equations will considerably distort the error distribution and render simple unweighted linear regression inappropriate. The ease of incorporating extra parameters into standard equations when nonlinear regression is used is further illustrated by fitting enzyme reaction data which describe a first-order process when a significant nonspecific background is present. For this equation no simple rearranged linear plot is possible, but nonlinear regression is easily applied to determine the kinetic parameters. PMID- 2327572 TI - Rapid and serial determination of protein kinase C activity and of the associated [3H]PDBu binding using a 96-well microtiter plate and a cell harvester. AB - We propose a serial assay of both protein kinase C activity and the related [3H]phorbol 12,13-dibutyrate binding, each carried out in 96-multiwell dishes, started and stopped row by row using a multipipet. Protein kinase C activity is observed through the transfer of the gamma-phosphoryl group of radioactive ATP onto histone H1 type III-S. Enzymatic reactions are started by adding enzyme extracts and stopped by adding trichloroacetic acid. Acidic precipitates of each row are simultaneously collected on glass fiber paper using a cell harvester. The addition of bovine serum albumin and cold ATP at the end of the reaction and the addition of trichloroacetic acid in the washing fluid lead to a high recovery of protein kinase C activity and reproducible results. Measurement of [3H]phorbol 12,13-dibutyrate binding to protein kinase C was carried out in a mixed micellar solution as described elsewhere (Y. Hannun and R. M. Bell (1987) in Methods in Enzymology, Vol. 141, pp. 287-293). The quaternary complex formed from protein kinase C, phosphatidylserine, calcium, and [3H]phorbol 12,13-dibutyrate was then bound to a beaded anionic exchanger which was automatically separated from the free phorbol 12,13-dibutyrate by microfiltration using a cell harvester. The binding reaction was highly calcium- and phosphatidylserine-dependent and calcium had to be added to washing fluid for optimal recovery. Determination of protein kinase C activity and phorbol 12,13-dibutyrate binding gave results similar to those of other published methods and the signal/noise ratio was greatly increased. Using a semi-automated cell harvester, the system is partially automated and provides accurate and reproducible results. PMID- 2327573 TI - Photochemical crosslinking in oligonucleotide-protein complexes between a bromine substituted 2-5A analog and 2-5A-dependent RNase by ultraviolet lamp or laser. AB - 2',5'-oligoadenylates known as 2-5A [px(A2'p)nA; chi = 2 or 3, n greater than or equal to 2] are produced in interferon-treated cells in response to double stranded RNA. 2-5A binds with high affinity to a 2-5A-dependent RNase resulting in the cleavage of single-stranded RNA. An efficient, rapid, and extremely sensitive photoaffinity labeling method was developed to facilitate detection of 2-5A-dependent RNase. A bromine-substituted and radioactive derivative of 2-5A, the 5'-monophosphate, p(A2'p)2(br8A2'p)2A3'-[32P]Cp, was synthesized as probe for 2-5A-dependent RNase. Even though this bromine-substituted analog of 2-5A bore no 5'-terminal triphosphate or diphosphate, it bound to 2-5A-dependent RNase with the same high affinity as did 2-5A per se but it was a less effective activator of the RNase under the present assay conditions. The presence of bromine atoms in the 2-5A analog enhanced by more than 200-fold crosslinking to 2-5A-dependent RNase under a uv lamp; many additional polypeptides were also labeled but at much lower levels. Furthermore, using high-intensity uv laser irradiation (308 nm) covalent attachment of the bromine-substituted 2-5A analog to 2-5A-dependent RNase was readily achieved within 10(-6) s. PMID- 2327574 TI - Purification of eucaryotic extrachromosomal circular DNAs using exonuclease III. AB - A method for the isolation of eucaryotic extrachromosomal circular (ecc) DNA is described. Exonuclease III was used to preparatively digest linear and open circular forms of DNA; the resultant exonuclease-resistant molecules were then characterized by buoyant density gradient sedimentation and were found to be essentially covalently closed circular DNA. The efficiency of the exonuclease method was compared to ultracentrifugation techniques and was found to give yields greater than those obtained by two or more equilibrium density gradients. The utility of the exonuclease III technique was determined by purifying eccDNAs from mouse liver, brain, heart, and kidney tissues. The results showed that there are tissue-related differences in eccDNA content. PMID- 2327575 TI - A simple enzymatic method for the preparation of radiolabeled erucoyl-CoA and other long-chain fatty acyl-CoAs and their characterization by mass spectrometry. AB - A simple two-step method for the biosynthesis of radiolabeled erucoyl-coenzyme A of high specific activity and other long-chain fatty acyl-coenzyme A (acyl-CoA) thioesters is reported. 1-14C-labeled erucic and oleic acids, as well as unlabeled ricinoleic and nervonic acids, were incubated at 35 degrees C with coenzyme A in the presence of ATP, MgCl2, and acyl-CoA synthetase (EC 6.2.1.3) from Pseudomonas spp. to yield the corresponding CoA thioesters. Following incubation, each thioester was purified by rapid passage through a disposable reverse-phase C18 extraction column. The overall yields were greater than 90% and the purities greater than 95%, based on the distribution of radioactivity, and chromatographic and spectral properties. Fast ion bombardment-mass spectrometry was employed to confirm the structures of the various acyl-CoAs. PMID- 2327576 TI - Reaction of alpha-tubulin with iodotyrosines catalyzed by tubulin:tyrosine ligase: carboxy-terminal labeling of tubulin with [125I]monoiodotyrosine. AB - We have studied the capacity of different iodinated derivatives of phenylalanine and tyrosine to inhibit the incorporation of [3H]tyrosine into tubulin catalyzed by tubulin:tyrosine ligase. In contrast to thyronine and its iodinated derivatives, iodotyrosines were efficient inhibitors. That they also functioned as substrates of the enzyme was shown by the effective incorporation of [125I]mono- and diiodotyrosine into tubulin. The label was shown to be located at the carboxy terminus. Labeling by this method conserves the polymerization capacity of tubulin in contrast with classical radioiodination methods involving oxidation. PMID- 2327577 TI - Synthesis and applications of 8-azido photoaffinity analogs of P1,P3-bis(5' adenosyl)triphosphate and P1,P4-bis(5'-adenosyl)tetraphosphate. AB - 32P-labeled photoaffinity analogs of bis(5'-adenosyl)-tetraphosphate and bis(5' adenosyl)triphosphate which contain a single photoreactive 8-azidoadenosine group distal to the radiolabel have been synthesized from commercially available components using a combination of chemical and enzymatic procedures including a water-soluble carbodiimide. The method is simple, rapid, and produces yields of high specific activity products of around 60%. The analog of bis(5'-adenosyl) tetraphosphate is very similar to the parent compound in its inhibition of rat liver adenosine kinase and its efficiency as a substrate for the bis(5' nucleosidyl)tetraphosphate pyrophosphohydrolase from Artemia embryos. In the latter case, ATP and 8-azidoAMP are the preferred products. As would be expected, this analog is a much more effective photoprobe for both adenosine and adenylate kinases than the corresponding analog of bis(5'-adenosyl)triphosphate. Both compounds have been used to photoaffinity label crude extracts of Artemia, Vero cells, and Clostridium acetobutylicum and preferential specific labeling of different polypeptides by each analog has been shown. In extracts of C. acetobutylicum, the labeling of a polypeptide of Mr 48,500 by the bis(5' adenosyl)tetraphosphate analog was totally dependent on the presence of Co2+ ions. These compounds should therefore prove valuable both for the active site labeling of purified binding proteins and for the detection and identification of new target proteins for these nucleotides. PMID- 2327578 TI - Determination of reduced, oxidized, and protein-bound glutathione in human plasma with precolumn derivatization with monobromobimane and liquid chromatography. AB - This assay measures reduced (GSH), oxidized (GSSG, GSSR), and protein-bound (glutathione-protein mixed disulfides, ProSSG) glutathione in human plasma. Oxidized glutathione and ProSSG are converted to GSH in the presence of NaBH4, and, after precolumn derivatization with monobromobimane, GSH is quantitated by reversed-phase liquid chromatography and fluorescence detection. The NaBH4 concentration is optimized so that total recovery of oxidized glutathione is obtained and no interference with the formation/stability of the GSH-bimane adduct occurs. The presence of 50 microM dithioerythritol prevents reduced recovery at low concentrations of GSH, and the standard curve for GSH is linear over a wide concentration range and is super-imposed upon that obtained with GSSG. Selective determination of oxidized glutathione exploits the fact that N ethylmaleimide (NEM) blocks free sulfhydryl groups and excess NEM is inactivated by the subsequent addition of NaBH4. To measure total glutathione including the protein-bound forms, the protein is solubilized with dimethyl sulfoxide, which is compatible with the other reagents and slightly increases the yield of the fluorescent GSH derivative. The assay is characterized by a sensitivity (less than 2 pmol) sufficiently high to detect the various forms of glutathione in plasma, by an analytical recovery of GSH and GSSG close to 100%, and by a within day precision corresponding to a coefficient of variation of 7%. The assay was used to determine the dynamic relationships among various glutathione species in human plasma. PMID- 2327579 TI - High-performance liquid affinity chromatography and in situ fluorescent labeling on thin-layer chromatography of glycosphingolipids. AB - A method combining high-performance liquid affinity chromatography and in situ fluorescent labeling on thin-layer chromatography is introduced for determination of glycosphingolipids. Glycolipids in crude extract from rat liver were separated quantitatively from neutral lipids and phospholipids with a phenylboronic acid derivatized silica gel column. Glycolipids were eluted quantitatively with approximately 98% of crude extract recovered. This column is useful for selective cleanup of glycosphingolipids in crude extract from tissue. Simultaneously, a fluorometric determination of glycosphingolipids with 7-amino-4-methylcoumarin after NaIO4 oxidation on a TLC plate was introduced and its condition was optimized. Glycolipids in amounts ranging from 1 to 100 pmol are easily detectable and give linear responses over the respective ranges. The method is fast and useful for the determination of glycolipids from small amounts of biological samples and requires a minimum amount of about 1 mg of biological specimen for determination of glycolipids. PMID- 2327580 TI - Nitrate analysis by capillary gas chromatography. AB - A microanalytical gas chromatographic (GC) method for the analysis of nitrate in rat urine is described. The method involves the conversion of nitrate to nitromesitylene and quantitation using 3,4-dimethylnitrobenzene as an internal standard. The nitroaromatics were separated on a wide-bore capillary column and detected with a nitrogen-phosphorus thermionic detector. The method exhibited linearity over the range of 1.0 to 1000 microM nitrate, and the detection limit was 0.5 microM nitrate (200-microliters sample). The coefficient of variation (CV) range for intra-day precision was 2.2 to 5.8% (20 microM level) and 3.1 to 6.5% (200 microM level). Inter-day CVs ranged from 2.0 to 6.1% for the samples tested. The average recovery was 77% (20 microM level) and 80% (20 microM level). The accuracy of the GC method compared favorably with results obtained from a standard colorimetric nitrate assay. Interference by urinary chloride was eliminated by pretreatment of samples with saturated silver acetate. Both processed and unprocessed samples were stable for at least 60 days at -15 degrees C. The procedure was used to measure urinary nitrate in rats fed a custom low nitrate diet. PMID- 2327581 TI - A competitive assay of lipoprotein: proteoglycan interaction using a 96-well microtitration plate. AB - A method for the microassay in vitro of lipoprotein: proteoglycan interactions is described. The wells of a plastic 96-well microtitration plate are coated with low density lipoprotein. A limiting quantity of biotin-conjugated proteoglycan is allowed to bind to each coated well, and the amount of the latter retained in wells is estimated spectrophotometrically through subsequent binding of alkaline phosphatase-conjugated avidin. Many of the incubation parameters (e.g., time, pH, salt concentration, divalent cations), which influence the extent of binding of biotin-conjugated proteoglycan, have been studied and optimized. The effect upon binding of introducing different levels of proteoglycans or lipoproteins at the interaction step can be measured readily. Thus, the orders of increasing relative binding affinities were found to be high density lipoprotein less than Lipoprotein (a) less than low density lipoprotein; rat chondrosarcoma proteoglycan less than bovine nasal cartilage proteoglycan less than human aorta proteoglycan; chondroitin 4-sulfate less than chondroitin 6-sulfate less than dermatan sulfate for lipoproteins, proteoglycans, and glycosaminoglycans, respectively. PMID- 2327582 TI - Chemical sensors for bedside monitoring of critically ill patients. PMID- 2327583 TI - In vitro percutaneous absorptiometry by simultaneous measurement using the photoacoustic method and absorbance. AB - A novel in vitro percutaneous absorptiometry utilizing a portable open-ended photoacoustic (PA) cell as the longitudinal diffusion cell was developed. With this system it was feasible to measure the reduction of drug applied to a membrane by the PA method and the amount of drug penetrating the membrane to the diffusion cell by absorbance, simultaneously in real time. A shikonin ointment prepared in a hydrocarbon vehicle was used as the model sample. The in vitro percutaneous absorptiometry was performed by means of a physiological saline solution and the skin of a hairless mouse. As a result, after the lag time the absorbance increased in proportion to time, whereas the PA signal reduced in proportion to the square root of time. As the signal obtained by the PA method corresponds to the amount of drug released from the ointment, a good correlation with Higuchi's theory is attained. Consequently, these results suggested the usefulness of this novel percutaneous absorptiometry technique which utilizes the PA method. PMID- 2327585 TI - Effect of reducing disulfide-containing proteins on electrospray ionization mass spectra. AB - Electrospray ionization produces multiply charged molecular ions for biomolecules with molecular weights in excess of 100,000. This allows mass spectrometers with limited mass-to-charge range to extend their molecular weight range by a factor equal to the number of charges. The maximum number of observed charges for peptides and smaller proteins correlates well with the number of basic amino acid residues (Arg, Lys, His), except for disulfide-containing molecules, such as lysozyme and bovine albumin. However, reduction of disulfide linkages with 1,4 dithiothreitol (Cleland's reagent) may allow the protein to be in an extended conformation and make "buried" basic residues available for protonation to yield higher charged molecular ions by the electrospray ionization process. For larger proteins reduction of disulfide bridges greatly increases the maximum charge state, but charging of basic amino acid residues remains less efficient than for smaller proteins. PMID- 2327584 TI - Surface-enhanced Raman analysis of sulfa drugs on colloidal silver dispersion. AB - Surface-enhanced Raman spectrometry (SERS) of three sulfa drugs (sulfadiazine, sulfamerazine, and sulfamethazine) is reported. Silver colloidal dispersions prepared by simple borohydride reduction of silver nitrate are used as substrates. The capability of SERS for spectral fingerprinting of analytes with close structural properties using easily prepared substrates and relatively simple instrumentation is illustrated. By careful attention to the timing in the measurement, quantitative information can be obtained from silver colloids. Linearity was achieved up to 100 ng mL-1. Limits of detection range in the low nanograms per milliliter level. PMID- 2327586 TI - Hadamard transform measurement of tandem Fourier-transform mass spectra. AB - The simultaneous collection of multiple spectra using tandem (MS/MS) and multidimensional (MS/MS/MS) mass spectrometry from multiple precursors is demonstrated to yield correspondingly enhanced sensitivity. This approach utilizes Hadamard transform deconvolution and takes advantage of the multichannel dissociation capability of Fourier-transform mass spectrometry. By application of this to an 11-component mixture, the 11 spectra of the products of dissociating 11 different combinations of six of the component molecular ions are measured; Hadamard transformation yields individual spectra of the precursor ions exhibiting a signal-to-noise improvement of 1.8x over spectra measured separately, as predicted by theory. Precursor ion selection with high specificity and product formation with high abundance reproducibility are critical; spurious peaks resulting from imperfect reproducibility can be minimized by using simultaneous equation coefficients reflecting the degree of precursor dissociation. Extension of this technique to MSn spectra is demonstrated with simultaneous MS/MS/MS monitoring of three precursors and three daughters yielding nine spectra representing the nine possible dissociation pathways. For MSn spectra, coding the product relationships for each additional step (e.g., precursor----daughter, daughter----granddaughter) requires elimination of half of the remaining ions. No ions are lost for coding in an improved Hadamard approach in which the combined daughter spectrum of the selected half of the precursors is subtracted from that of the other half. PMID- 2327588 TI - Stereoselective determination of free warfarin concentration in protein binding equilibrium using direct sample injection and an on-line liquid chromatographic system. AB - A new on-line high-performance liquid chromatography system was developed for the stereoselective determination of free drug concentration in drug-protein binding equilibrium. When a 40-300-microL portion of a sample solution containing 50-200 microM racemic warfarin (Wf) and 100-550 microM human serum albumin was directly injected into the internal-surface reversed-phase silica column, Wf gave a trapezoidal peak exhibiting a plateau region. The concentration in the plateau region was equal to the free Wf concentration in the initial sample solution. By the delivery of a portion (90 microL) of the eluent in the plateau region into the chiral separation column (Chiral AGP column) by column switching, the free concentrations of respective enantiomers of Wf were determined. The results agreed well with those obtained by the conventional ultrafiltration method. The precision was also confirmed by the within-run and day-to-day reproducibilities (coefficient of variation less than or equal to 3.05%, n = 5). The present method is simple and rapid and four sample solutions can be analyzed within 1 h without pretreatment. PMID- 2327587 TI - Flow injection analysis of L-lactate with enzyme amplification and amperometric detection. AB - A flow injection analysis method for the determination of the lactate anion with enzyme amplification and amperometric detection is described. The system utilizes an oxygen electrode for measurement of changes in the oxygen concentration in the flow stream. Two enzymes, lactate oxidase and lactate dehydrogenase, were randomly coimmobilized on aminopropyl controlled-pore glass (AMP-CPG) and packed into a reactor. beta-NADH was used as a coenzyme for the regeneration of lactate from pyruvate. The experimental conditions for the determination of the lactate anion were studied for this system by the simplex and the univariant methods. The results obtained under these two conditions were compared. The simplex experimental condition yielded a calibration curve whose linear portion had a slope that was 1.2 times greater than that of the linear portion of the curve obtained under univariant conditions. The limit of detection under simplex condition was 1.19 x 10(-7) M vs 3.29 x 10(-7) M lactate under univariant conditions. The relative standard deviation obtained for this system at 6 x 10( 6) M lactate (n = 10) was about 2.5% under simplex conditions and 3.6% under univariant maximization conditions. PMID- 2327589 TI - Gas chromatographic-mass spectrometric identification of four triene monoepoxides of arachidonic acid in human plasma. AB - Four triene monoepoxides of arachidonic acid have been identified as endogenous components of human plasma, the epoxy groups being in the 5,6-, 8,9-, 11,12- and 14,15-positions. Prior to trimethylsilylation and gas chromatographic-mass spectrometric analysis, both the expoxy and ester functions were reduced to hydroxy groups and the double bonds were hydrogenated catalytically. Saturation of the double bonds gave diagnostic spectra that were suitable for elucidating the position of the epoxy group. The shift in the fragmentation of a deuteriated sample verified the presence of the intact epoxides prior to chemical reduction. The presence of the double bonds in the epoxy molecules was demonstrated by reduction using homogeneous catalysis with tris(triphenylphosphine)rhodium(I) chloride and deuterium. PMID- 2327590 TI - Analysis of biological reference materials, prepared by microwave dissolution, using inductively coupled plasma mass spectrometry. AB - A procedure has been developed for the analysis of biological materials by inductively coupled plasma mass spectrometry (ICP-MS). Fast, efficient and complete sample digestion is achieved by a combined microwave-nitric acid/open beaker-nitric acid-hydrogen peroxide procedure. The ICP-MS analysis is performed with an on-line five-element internal standard to correct for matrix and instrumental drift effects. Results are presented for 24 elements in three biological reference materials (National Institute of Standards and Technology Standard Reference Materials 5277a Liver and 1566 Oyster and International Atomic Energy Agency Certified Reference Material H4 Animal Muscle). For all elements significantly above the detection limit and reagent blank concentrations, good agreement exists between ICP-MS and certified values. PMID- 2327591 TI - Determination of phosphorus in biological material using electrothermal atomisation atomic absorption spectrometry with a molybdenum tube atomiser. AB - Phosphorus has been determined by electrothermal atomisation atomic absorption spectrometry with a molybdenum tube atomiser. The effects of interferents on the phosphorus signal have been investigated. Chemical interferences were eliminated by high-temperature pyrolysis. The detection limit for the molybdenum tube system was 2.3 ng (corresponding to 2.3 micrograms ml-1 when 1 microliter was injected into the atomiser) and the characteristic mass was 1.9 ng of phosphorus. A calibration graph method combined with high-temperature pyrolysis has been evaluated through the determination of phosphorus in biological materials. The sensitivity, accuracy and precision of the method were superior to or nearly equal to those of graphite furnace atomic absorption spectrometry. The advantages of the high-temperature pyrolysis method are its simplicity and low cost. PMID- 2327592 TI - Pre-concentration of indolic compounds at a carbon paste electrode and indirect determination of L-tryptophan in serum by adsorptive stripping voltammetry. AB - The pre-concentration of indole and other indolic compounds of biochemical and pharmaceutical interest at a carbon paste electrode (Nujol/graphite) has been studied. All the compounds examined can be determined, by direct voltammetric measurements in their solutions, in the concentration range 1-8 microM. Indole, methylated indoles, harmaline and serotonin were accumulated at the electrode by a combined adsorption/extraction process. By applying the medium-exchange procedure, the accumulated compounds can be determined in the same concentration range, after a 60-s pre-concentration period, enhancing, therefore, the selectivity of the voltammetric determination. A procedure for the indirect determination of L-tryptophan in serum has been developed, which is based on these findings. L-Tryptophan was cleaved to indole by tryptophanase, and indole was subsequently determined voltammetrically after a 2-min pre-concentration period at the carbon paste electrode. From 0.3 to 1.2 micrograms of L-tryptophan in a total of 75 microliters of serum sample (20-80 microM) can be determined with an average error of ca. 0.03 microgram, whereas the recovery of added L tryptophan in serum samples is in the range 105-115%. PMID- 2327593 TI - Automated flow injection spectrophotometric determination of para- and meta substituted phenols of pharmaceutical interest based on their oxidative condensation with 1-nitroso-2-naphthol. AB - The reaction of para- and meta-substituted phenols with 1-nitroso-2-naphthol in the presence of either CeIV or PbIV as an oxidant has been used to develop a fast automated flow injection (Fl) method. A stopped-flow kinetic study of the reaction revealed the optimum conditions for the proposed Fl method. Acetaminophen, amoxicillin, cefadroxil, isoxsuprine, nylidrin, propylparaben, tyrosine and metaraminol can be determined in the range 1 x 10(-4)-8 x 10(-4) M, with relative standard deviations of less than 2%, and a measurement throughput of 40 measurements h-1. The method was evaluated by performing interference studies of common excipients and assaying commercial formulations of acetaminophen and isoxsuprine. The results were in good agreement with those obtained by acceptable spectrophotometric or high-performance liquid chromatographic methods (mean difference 2.1%). The high sample throughput of the Fl method was exploited by performing a content uniformity test of isoxsuprine tablets. PMID- 2327594 TI - The fiber composition of the abdominal vagus of the rat. AB - The present study provides a LM and EM inventory of the fibers of the rat abdominal vagus, including dorsal and ventral trunks and the five primary branches. Whole mounts (n = 15) were prepared to characterize the branching patterns. A set of EM samples consisting of both trunks and all branches (i.e. dorsal and ventral gastric, dorsal and accessory celiac, and hepatic) were then obtained from each of six additional animals. A complete cross-sectional montage (x 10000) was prepared from each sample. All axons were counted, and greater than 10% of them were evaluated morphometrically. The means of unmyelinated axon diameters for each of the five branches were similar (0.75-0.83 microns). However, the shapes of the fiber size distributions, as summarized by their skew coefficients, revealed that the two gastric branches differed significantly from the two celiac branches; furthermore, the hepatic size distribution differed from all others. Most of the myelinated fibers (85%) in all branches were less than 2.6 microns in diameter and had sheath widths between 0.1 and 0.5 micron. The gastric branches, however, also contained a few larger myelinated fibers with sheath widths as great as 0.85 micron. Whole mounts revealed fibers which were not of supradiaphragmatic origin within all five vagal branches; these adventitial bundles were traced along the perineurium between adjacent branches. The sum of the fibers in the five branches (26930) was 21% more than the number counted in the parent trunks (22272); this excess probably reflects the adventitial fiber content. The whole mounts also showed that a large and regularly positioned paraganglion was associated with the dorsal branches. The structural profiles observed (i.e. unmyelinated and myelinated fibers size distributions, presence of extrinsic fascicles, glomus tissue content, etc.) differentiate the vagal branches into three morphologically distinct sets: a gastric pair, a celiac pair, and a hepatic branch. The fiber counts, when considered with observations of the numbers of efferents and adventitial fibers in the nerve, suggest that the percentage of efferent fibers is much higher than in all the widely accepted estimates found in the literature: efferent fibers may represent over a quarter of the total number of fibers. PMID- 2327595 TI - The development of the human placental villous tree. AB - The present investigation was undertaken in order to achieve a better understanding of the dynamics of placental villous differentiation. Villous trees from human placentas from different stages of pregnancy (first trimester to full term) were isolated and studied by light microscopy and scanning electron microscopy. For light microscopy the trees were serially sectioned and two dimensionally reconstructed. For scanning electron microscopy complete villous trees or freeze-cracked villi were studied. The most important finding was that the mesenchymal villi are continuously newly formed out of the trophoblastic sprouts throughout pregnancy. Because of this they exist in all stages of pregnancy and have to be considered the basis for growth and differentiation of the villous trees. In the first two trimesters they are the forerunners of the immature intermediate villi, whereas in the last trimester the mesenchymal villi are transformed into mature intermediate villi. The immature intermediate villi formed during the first two trimesters are developmental steps towards the stem villi. On the other hand, the mature intermediate villi, which only are developed during the last trimester, produce numerous terminal villi. The latter are not active outgrowths caused by proliferation of the trophoblast, but rather passive protrusions induced by capillary coiling due to excessive longitudinal growth of the fetal capillaries within the mature intermediate villi. PMID- 2327596 TI - The production of mouse fetal-placental chimeras using trisomy 16 and euploid blastocysts. AB - By means of a combination of immunosurgery and a modified method of microsurgery, blastocysts were reconstructed to produce viable chimeric fetal-placental units. Reciprocal reconstituted blastocysts were produced using euploid and trisomy 16 blastocysts. Reconstructed blastocysts yielded significantly smaller fetuses at day 17 of pregnancy than simultaneously transferred control blastocysts (mean body weight 0.49 g vs 0.64 g, P less than 0.01). However, apart from reduced size, no abnormalities were observed for any euploid fetus-euploid placenta construct. The three reconstructed blastocysts that yielded a trisomic fetus trisomic placenta were viable when examined on day 17 and displayed the abnormalities typical of mouse trisomy 16. No reconstructed blastocyst that yielded a trisomic fetus-euploid placenta or a euploid fetus-trisomic placenta was viable beyond day 13 of development. One case in which a trisomic fetus had a placenta that was chimeric (euploid/trisomic) examined on day 17 displayed the abnormalities typical of a trisomic fetus but the placenta appeared histologically normal. The findings suggest that there is a coordination of the development of the fetus and the placenta that is essential for the development of the fetus. PMID- 2327597 TI - Development of topographic connections between the isthmic nuclei and optic tecta in the frog Limnodynastes dorsalis. AB - In the frog Limnodynastes dorsalis, the pattern of topographic connections between the isthmic nuclei and optic tecta was determined by anterograde and retrograde transport of horseradish peroxidase from localised tectal regions. In both larvae and adults, reciprocal mapping of the uncrossed isthmo-tectal and tecto-isthmal projections was evidenced by the juxtaposition of labelled tecto isthmal terminations with labelled cells in the cortex and medulla of the ipsilateral isthmic nucleus. The crossed isthmo-tectal projection was revealed by labelled cells in the cortex and medulla of the nucleus contralateral to the injection. In adults, rostral tectal areas projected to rostral and ventral regions of the ipsilateral isthmic nucleus. Following more caudal tectal injections, labelled cells were found in progressively more dorsal locations within the nucleus. Labelled cells in the contralateral nucleus were found in the rim cortex abutting a neuropil and in medullary cells adjacent to this region. Connections between ventral isthmic regions and most rostral tectum and between dorsomedial nucleus and caudomedial tectum were similar in both nuclei. However, for isthmic areas projecting to rostromedial and mid-tectum, the location of labelled cells in the contralateral nucleus was inverted with respect to the ipsilateral nucleus. This inversion would allow both nuclei to project to visually corresponding regions of each tectum. During larval stages the basic adult topography was established despite the continued neurogenesis of both isthmic nuclei and optic tecta. In late larval stages a rim neuropil appeared adjacent to the cortical region in the isthmic nuclei where labelled cells of the crossed isthmotectal projection were found. Prior to this stage labelled cells abutted labelled medullary cells. The appearance of this neuropil was approximately temporally correlated with the onset of electrophysiologically detectable responses in the ipsilateral visuotectal projection. Formation of the rim neuropil may relate to maturation of the tecto-isthmo-tectal connections which underlie this visual projection. PMID- 2327599 TI - Harderian gland and the lacrimal gland of the lizard Podarcis s. sicula: histology, histochemistry, and ultrastructure. AB - Histology, histochemistry, and ultrastructure of the Harderian gland and lacrimal gland of the lizard Podarcis s. sicula were investigated. The Harderian gland, located at the medial corner of the orbit, can be divided into three zones showing different tinctorial features either with Mallory or hematoxylineosin stains. The glandular cells of the acinar medial zone secrete predominantly acidic sulphated mucosubstances. The acinar cells of the intermediate zone contain secretory granules that show a weak reaction to the histochemical tests for mucosubstances. The lateral zone has a tubulo-acinar type of structure and tests strongly for proteins, whereas Alcian-PAS staining is very weak. The lacrimal gland is smaller than the Harderian gland and lies in the region of the posterior commissure of the eyelids. it shows the same histological and histochemical characteristics of the medial zone of the Harderian gland, i.e., it is mucous secreting. At the ultrastructural level the zonation is well defined, especially when the secretory granules are examined. Granules of the mucoid type are found in the lacrimal gland and the medial zone of the Harderian gland. The secretory granules of the lateral part of the Harderian gland show a composite structure never described before. Therefore, they have been called "special secretory granules." Each of these granules is composed of three sharply separated components. It is not known whether the three components correspond to different secretions. Histochemical tests suggest that they are of the serous type. Both mucous and serous granules are secreted by the same glandular cells of the intermediate zone of the Harderian gland. The two types of granules usually occupy different cell compartments. The mechanism of secretion appears either merocrine or apocrine in both the Harderian gland and the lacrimal gland. PMID- 2327600 TI - Calcification capacity of dental papilla mesenchymal cells transplanted in the isogenic mouse spleen. AB - The capacity of the dental pulp to form calcified tissue was examined in papilla cells dissociated from first molar tooth germs of the neonatal mouse and isografted in the spleen for up to 7 days. To obtain papilla cell populations without odontoblasts, pulpal mesenchyme was isolated mechanically from the enamel organ after 0.1% trypsin treatment and rolled on a membrane filter. On day 3 after transplantation, the grafted papilla cells had changed into large, spindle shaped cells, and initial calcification with needle-like crystals began in association with the collagenous matrix surrounding those cells. On day 7 after transplantation, the spindle cells transformed into odontoblast-like cells containing well-developed secretory organelles, and irregular, but nontubular, calcified tissues were commonly observed surrounding the extracellular collagenous matrix. The calcified tissue matrix with cellular inclusions displayed a structure similar to that of osteodentin. During this period, an intense positive reaction for alkaline phosphatase (ALPase) activity was demonstrated along the cell membranes of the odontoblast-like cells aligned at the periphery of forming calcified tissue. Enzymatic activity could not be detected on the cells incorporated completely into osteodentin-like matrix. The present results show that the papilla cell population transplanted into the spleen formed osteodentin-like material, thus demonstrating the capacity of papilla cells to produce calcified tissue. PMID- 2327601 TI - Morphometric study of the microvasculature of the main excretory duct subepithelia of the rat parotid, submandibular and sublingual salivary glands. AB - This study investigated the relationship between the fine structure of the main excretory duct (MED) epithelia and the subepithelial capillaries of the major salivary glands (parotid, submandibular, and sublingual) in the rat. The MED subepithelial capillaries vary in type (fenestrated and continuous), number of fenestrae present in the available fenestrated endothelium (the attenuated area of endothelium), and number of capillaries per unit length of epithelium. In the parotid gland, continuous capillaries predominate, and the capillary density per 200 microns of epithelium (1.73 in region I and 1.03 in region II) is lower than in the other two glands, as is the number of fenestrae per 10 microns of available endothelium (1.97 in region I and 1.25 in region II). The submandibular gland has mainly fenestrated capillaries. The capillary density per 200 microns of epithelium (4.46 in region I and 5.51 in region II) is higher than in the other two glands, as is the number of fenestrae per 10 microns of available endothelium (4.82 in region I and 7.90 in region II). Similarly, in the sublingual gland, fenestrated capillaries are dominant. The density of capillaries per 200 microns of epithelium (4.15 in region I and 4.31 in region II) is intermediate between the parotid and submandibular glands, as is the number of fenestrae per 10 microns of available endothelium (2.98 in region I and 3.83 in region II). PMID- 2327598 TI - Afferent connections of the nucleus centralis amygdalae. A horseradish peroxidase study and literature survey. AB - The central nucleus of the amygdala has been shown to be involved in cardiovascular regulation and the integration of arousal. In this study, the afferent input was investigated in cat by microinjecting horseradish peroxidase (HRP) into the central nucleus and examining retrogradely-labelled cells in the brain. Retrograde labelling was found in the cortex next to the sulcus ectosylvius anterior, fissura lateralis Sylvii, sulcus rhinicus anterior and posterior, sulcus suprasylvius, and pyriform and entorhinal cortices as well as in the insula and claustrum. Each of the sub-nuclei of the amygdaloid complex exhibited retrogradely-labelled perikarya. Labelled cells were also found in the diagonal band of Broca, nucl. lateralis septi, and nucl. proprius striae terminalis (bed nucl. of stria terminalis). In the hypothalamus the area preoptica medialis and lateralis, nucl. dorsomedialis, paraventricularis, periventricularis, arcuatus and mammilaris medialis were labelled. The nucl. subthalamicus, zona incerta, peripeduncular system, substantia nigra, and nucl. interpeduncularis contained HRP-marked cells. In the thalamus labelled cells were observed in the nucl. reuniens, nucl. centroposterior lateralis, nucl. latero posterior, nucl. posterior, nucl. centro-anterior, antero-dorsalis, antero medialis, antero-lateralis, centrum mdianum, nucl. reticularis, nucl. rhomboideus, nucl. parafascicularis and subfascicularis. The area tegmentalis Tsai and the corpora geniculata also contained labelled cells. In the brain stem, HRP-marked cells could be detected in the brachium colliculi inferioris, aqueductal grey matter, locus coeruleus, nucl. parabrachialis, in various nuclei of the formatio reticularis, in the nucl. retrofascialis, nucl. solitarius, nucl. commissuralis, nucl. ambiguus and nucl. dorsalis n. vagi. The results were compared to other neuroanatomical studies and to functional studies of the amygdala. PMID- 2327602 TI - SEM and TEM analyses of isolated human retinal microvessel basement membranes in diabetic retinopathy. AB - Human retinas from persons with diabetic retinopathy and age-matched controls were rendered acellular by sequential detergent treatment. The resulting network of microvascular extracellular matrix (ECM) materials, including basement membranes (BMs), was compared by TEM and, following cryofracture, by SEM. Our study demonstrates that in diabetics, retinal capillary BM complexes are generally thickened and that their ECM subcomponents, including BM leaflets and BM-like pericytic matrix (PCM), are differentially altered. Two diabetic microvessel types were identified. In type A vessels, ECM expansion is manifested by loosely arranged combinations of concentric PCM layers and collagen fibrils with thickened subendothelial (EBM) and pericyte (PBM) BM leaflets. Type B vessels show densely compact central PCM masses and poorly recognizable EBMs and PBMs. In both types, Muller cell BMs (MBMs) are relatively unaffected. High resolution SEM shows tissue-specific features in normal EBM and MBM surfaces, but disease-related topographic changes are not evident. It is possible that the ECM arrangements identified in our study relate to different microvessel domains and that their specific morphological features may play important roles in the pathogenesis of diabetic retinopathy including capillary closure and neovascularization. PMID- 2327603 TI - Patterns of skeletal histologic change through time: comparison of an archaic native American population with modern populations. AB - This paper compares patterns of histologic change in an archaic Native American population with those in modern white populations. Histologic sections were removed from core biopsies taken from the anterior femoral cortex of an archeologic sample of Pecos Indians. The data demonstrate many microstructural similarities between the Pecos and modern populations, even though they were genetically and culturally distinct. Pecos women had small Haversian canals and large osteon mean wall thickness, with no clear evidence of an intracortical bone volume deficit even in the older age groups, although significant marrow cavity expansion occurred in both males and females with age. No striking relationships were found between bone tissue changes and gross geometric changes with age. The data suggest that a more active life-style is associated with greater osteon mean wall thickness or osteon population density, but that it alone does not protect against significant bone loss on the cortical-endosteal surface. PMID- 2327604 TI - Remission of the polycystic ovarian condition (PCO) in the rat following hemiovariectomy. AB - The estradiol valerate-induced polycystic ovarian condition in the rat represents a normal ovarian response to aberrant endocrine stimuli. Although we have shown that removal of one polycystic ovary (hemiovariectomy) results in restoration of cyclicity and normal morphology in the remaining ovary by 1 week, nothing is known about the process of recovery or about the role of the hypothalamo pituitary unit in initiating recovery. We have therefore examined ovaries at 3, 12, 24, 48, and 120 hours following removal of the contralateral polycystic ovaries. The ovarian content and size distribution of healthy and atretic follicles was determined, as well as the occurrence of follicular cysts, type III large follicular structures, and corpora lutea. The plasma LH pattern was also examined at a short postoperative interval. At 3 hours, there was a significant increase in mean ovarian weight that coincided with the emergence of healthy large secondary follicles. By 12 hours, there was a significant sustained diminution in the number of atretic follicles of all sizes, but the total number of healthy follicles did not increase significantly until 120 hours. The cystic follicles had all but disappeared by 120 hours because of mechanical compression by newly developing ovarian tissue. Ovarian recovery is, therefore, biphasic, consisting of a very early diminution in atresia coincident with, and perhaps caused by, a major alteration in the plasma LH pattern. The second phase is characterized by a wave of follicular recruitment and development. PMID- 2327605 TI - Smooth muscle cells of neural crest origin form the aorticopulmonary septum in the avian embryo. AB - Previous studies have shown that the cells of the aorticopulmonary (AP) septum are similar to the smooth muscle cells of the mediae of the great vessels in their common origin from the cardiac neural crest and in their common expression of an elastic extracellular matrix. The purpose of this study was to test the cells of the AP septum for the presence of certain cytoplasmic proteins, especially smooth muscle alpha-actin (SMAA) whose presence is definitive of smooth muscle. A monoclonal antibody against SMAA was applied to normal chicken embryos at 3.5-8 days of incubation and to age-matched embryos from which the cardiac neural crest had been ablated surgically. Antibodies against the intermediate filaments desmin, cytokeratin, and vimentin also were applied. The results showed that the AP septal cells expressed SMAA during the process of septation, days 5-8; but when the cardiac neural crest was ablated and septation was defective, no cells in the conotruncal connective tissue expressed SMAA. None of the intermediate filament proteins were detected in the septum. These results indicate that the AP septal cells are smooth muscle and therefore may be hypothesized to have an active role in septation. PMID- 2327606 TI - Effect of occlusal functional forces on incisor socket morphology and location in the rat mandible. AB - The effect of functional occlusal stress on dimensional alterations of the rat incisor socket and mandible were studied from roentgenograms. In 12 rats, the lower left incisor was shortened twice weekly, whereas the lower right incisor was allowed to remain in contact with both upper incisors. Thus, the right incisors were subjected to hyperfunction, and the left ones, to hypofunction. The lower incisors of 16 rats with normal occlusal contact served as control. Following an experimental period of 3 months, the animals were killed and standardized radiographs were taken of the cleaned mandibles. Socket and mandibular dimensions were measured on magnified tracings of the roentgenograms. Socket area, its posterior length, posterior mandibular length, and gonial angle changed in the same direction under both hyper- and hypofunction. The anterior socket was relocated in opposite directions: under hyperfunction, it assumed a more inferior position, whereas in hypofunction, it moved superiorly. The angulation of the socket became significantly more acute under hyperfunction, whereas in hypofunction, this parameter remained unchanged. It is concluded that altered functional demands affect the morphology of the incisor socket and its location within the mandibular borders. PMID- 2327607 TI - Changes in mesenchymal cell and hyaluronate distribution correlate with in vivo elevation of the mouse mesencephalic neural folds. AB - The mesenchyme of the elevating mesencephalic neural folds of the mouse is composed primarily of mesenchymal cells embedded in an hyaluronate-rich extracellular matrix. In this study we provide evidence that hyaluronate and mesenchymal expansion may play a role in neural fold elevation and closure. Spatial and temporal patterns of mesenchymal cell and hyaluronate distribution were analyzed during neural fold elevation and closure using the computer assisted method of smoothed spatial averaging and established methods of image processing. Degree of fold elevation and fold shape changes were analyzed using standard morphometric measures. The results of these analyses defined five distinct stages in mesencephalic neural fold elevation and closure. Mesenchymal cells and hyaluronate were found in a non-random distribution within the neural fold and showed distinct patterns of distribution which could be correlated with specific stages in neural fold elevation. The results of these analyses suggested that the elevation of the mesencephalic neural folds is produced by the expansion of an hyaluronate-rich extracellular matrix in the central mesenchyme which under the direction of surrounding tissues pushes the folds mediad towards the dorsal midline. PMID- 2327608 TI - X-chromosome monosomy in the myelin-deficient rat mutant. AB - We have identified three examples of female Wistar rats exhibiting the tremor and seizures characteristic of the X-linked myelin deficiency (md) mutation, which is ordinarily seen only in males. Cytogenetic study of two of these animals has shown them to have 41 chromosomes instead of the normal 42. The missing chromosome was identified as an X chromosome by G-banding analysis. These animals thus have an XO genotype comparable to that in Turner's syndrome. Anatomically, one of the animals, which was studied in detail, showed no abnormality of the uterus, and the ovaries, although somewhat smaller than normal, were histologically indistinguishable from those in a normal female rat. No evidence of endocardial fibroelastosis was detected, nor was there any anomaly of the aorta. The myelin deficiency in the central nervous system was comparable to that in hemizygous mutant male rats. XO monosomy in the Wistar rat thus has little effect on phenotype and is more comparable to that in mice than to Turner's syndrome in man. The myelin-deficient rat is useful for studies of X-chromosome monosomy since XO females can readily be identified by the neurological syndrome characteristic of the md mutation. PMID- 2327609 TI - Ultrastructural localization of pemphigus vulgaris antigen on canine keratinocytes in vivo and in vitro. AB - Pemphigus antigens were localized, by use fo immunoelectron microscopy, on canine keratinocytes in vivo on esophageal mucosa and in vitro on established cultured keratinocytes. Convalescent sera from a human being with pemphigus vulgaris and a human being with pemphigus foliaceus reacted with the interdesmosomal cytoplasmic keratinocyte membrane of canine esophagus. Cultured canine keratinocytes expressed the pemphigus vulgaris antigen in a similar pattern, but did not carry the pemphigus foliaceus antigen. The differential presence of cell surface antigens and its relation to various forms of the disease are discussed. PMID- 2327610 TI - Effects of antibiotics on phagocyte recruitment, function, and morphology in the bovine mammary gland during the early nonlactating period. AB - The effects of 2 antibiotic preparations administered intramammarily on phagocyte recruitment, function, and morphology were evaluated at the beginning of the nonlactating period. Twelve cows with no clinical or microbiologic evidence of mastitis were assigned to 1 of 2 treatment groups. At the end of lactation, 1 of the antibiotic preparations was infused in a fore- and hind quarter of each cow; the remaining quarters were untreated controls. One group was given benzathine cephapirin; the second group was given sodium novobiocin. Secretion samples were collected from 1 treated and 1 control quarter at 16 hours, and from the remaining 2 quarters at 64 hours after treatment. Total and differential somatic cell counts were determined, and morphology of mammary polymorphonuclear neutrophils (PMN) and macrophages was observed by transmission electron microscopy. In vitro ingestion and killing of Staphylococcus aureus by mammary PMN and macrophages were assessed by fluorescent microscopy, using acridine orange stain. Cells resident in a fixed volume of secretion were incubated with a known concentration of S aureus. Total cell and PMN concentrations were higher in treated than in control quarters. Neutrophils were the predominant cell type in both treated and control quarters over the sampling period. As measured in this study, in vitro ingestion and killing of S aureus by individual PMN from treated quarters was reduced. Antibiotic treatment also increased the proportion of morphologically abnormal phagocytes. There were significant correlations among PMN ingestion, killing, and morphology. However, increased PMN concentrations tended to compensate for the reduced phagocytic function of individual cells. Therefore, efficacy of antibiotic treatment of nonlactating cows may depend, at least in part, on increased PMN concentration, which may tend to compensate for reduced phagocytic function. Compared with PMN, macrophages appeared to have only a minor role in phagocytosis of bacteria. PMID- 2327611 TI - Bovine monoclonal antibodies specific for bovine herpesvirus-1 glycoprotein gIII. AB - Spleen cells from a calf immunized with bovine herpesvirus-1 (BHV-1) were fused with the nonsecreting murine cell line SP2/0. Several bovine-murine hybridomas secreting bovine immunoglobulins were stabilized. Of these, 9 hybridomas secreted bovine monoclonal antibodies that specifically bound to BHV-1 in a radioimmunoassay. Two of these monoclonal antibodies reacted specifically with BHV-1 in an indirect fluorescent antibody test and immunoprecipitated a BHV-1 glycoprotein with molecular mass of 97 kilodaltons. PMID- 2327613 TI - Serum IgG antibody concentrations against environmental microbes in mares and foals during different seasons and effect of stabling practices. AB - Over periods of 22 and 14 months, IgG antibody concentrations in serum samples obtained monthly from 14 mares and 19 foals, respectively, were measured by use of ELISA against antigens of the following environmental microbes: Aspergillus umbrosus, Penicillium brevicompactum, Rhodotorula glutinis, Absidia corymbifera, Aspergillus fumigatus, Humicola grisea, Micropolyspora faeni, and Thermoactinomyces vulgaris. The mares and foals were on pasture from early June until early October, then were stabled during the winter season until the following June. In the mares, increased antibody concentrations against most microbes were observed typically in midwinter and late spring when the horses were stabled; antibody concentrations against R glutinis, however, peaked in August. Concentrations differed between the summer and winter seasons and, in most instances, between 2 consecutive years and correlated with amounts of rainfall during the previous harvest season. In the foals, circulating passively acquired antibodies disappeared within 3 to 4 months after birth. During the first year of life, substantially increased autogenous antibody concentrations were observed only against R glutinis. Antibody concentrations against the other microbes increased gradually toward the end of the indoor season. In a group of foals transferred indoors in autumn, 6 weeks later than the other foals, antibody concentrations were lower when measured in December. Results supported the view that, to minimize exposure to microbial spores during the winter season, horses should be kept outdoors as much as possible and attention should be focused on improving the ventilation in stables and the quality of feeds and beddings. PMID- 2327612 TI - Influence of recombinant human interleukin-2 administration on lymphocyte and neutrophil function in clinically normal and dexamethasone-treated cattle. AB - Recombinant human interleukin-2 (rhIL-2) was evaluated for its influence on total and differential WBC counts, lymphocyte blastogenic responsiveness to mitogens, and several measurements of neutrophil function in clinically normal and in dexamethasone-treated cattle. A single dose of rhIL-2 (2.5 X 10(7) U) given SC had no influence on the total or differential WBC count; however, it did cause an inhibition of neutrophil random migration. The other measurements of neutrophil function (Staphylococcus aureus ingestion, cytochrome C reduction, iodination, and antibody-dependent and antibody-independent cell-mediated cytotoxicity) evaluated were not significantly altered. The rhIL-2 treatment was associated with a significant (P less than 0.01) decrease in uptake of [3H]thymidine in unstimulated lymphocytes and a tendency toward enhanced blastogenesis of lymphocytes stimulated with phytohemagglutinin. This enhancement was significant (P less than 0.05) only when the results were expressed as a stimulation index. Lymphocyte responsiveness to concanavalin A and pokeweed mitogen was not significantly influenced by rhIL-2 administration. Dexamethasone (0.04 mg/kg) administered every 24 hours for 3 consecutive days altered the WBC count and several measurements of lymphocyte and neutrophil function. The administration of a single dose of rhIL-2 (2.5 X 10(7) U) 8 hours after the first dose of dexamethasone did not alter the influence of dexamethasone on any of the measurements. These results indicated that rhIL-2 has some biologic activity in cattle, but when used as administered here, did not overcome the influence of dexamethasone on the in vitro measurements of lymphocyte and neutrophil function that were evaluated. PMID- 2327614 TI - Influence of tolazoline on caudal epidural administration of xylazine in cattle. AB - Eight adult female cattle (6 Holstein, 1 Jersey, 1 Brown Swiss) were used to determine the antagonistic effects of tolazoline, and alpha 2-adrenoceptor antagonist, on xylazine-induced (via caudal epidural administration) depression of CNS, respiratory, and cardiovascular activity and rumen motility. A 2% solution of xylazine HCl was injected into the epidural space at the first coccygeal interspace, using a dosage of 0.05 mg/kg of body weight, diluted to a 5 ml volume with sterile water, and administered at a rate of approximately 1 ml/30 s. Eight minutes after xylazine injection, either tolazoline (0.3 mg/kg) or saline solution (4 ml) was administered IV. All 8 cattle were treated, using both regimens in a random sequence; at least 1 week elapsed between treatments. Epidurally administered xylazine induced caudal analgesia (S3 to coccyx), as evaluated by no response to superficial and deep muscular pinprick, and induced sedation, cardiopulmonary depression, and inhibition of rumen motility, but all cattle remained standing. Tolazoline effectively reversed xylazine-induced rumen hypomotility, and partially antagonized xylazine-induced cardiopulmonary depression without affecting sedation and desirable local (S3 to coccyx) analgesic effects. PMID- 2327615 TI - Myoelectric activity of the ileum, cecum, and right ventral colon in ponies during interdigestive, nonfeeding, and digestive periods. AB - Myoelectric activity of the ileum, cecum, and right ventral colon (RVC) was studied in 4 mature ponies. Eight Ag-AgCl bipolar recording electrodes were sutured to the seromuscular layer of the ileum (2 electrodes), cecum (4 electrodes), and RVC (2 electrodes). Myoelectric activity was studied beginning 10 days after surgery. Eight, 60-minute recording sessions were performed in each pony during the interdigestive period, which was the period 3 to 7 hours after the morning feeding. On separate days, food was withheld for 24 hours, and 90 minute recordings were obtained during the nonfeeding period. Ponies were then fed a normal ration, and recordings were continued to obtain data for the digestive (feeding) period. All phases of the migrating myoelectric complex were seen at both ileal electrodes during the interdigestive period, including the periods of no spiking activity (phase 1), irregular spiking activity (phase 2), and regular spiking activity (phase 3). Phase 2 occupied 77% of the total recording time, and the mean duration of phases 1, 2, and 3 was 3.4 +/- 0.2, 12.8 +/- 1.2, and 6.7 +/- 0.7 min, respectively. Frequency of ileal slow waves was 11.8 +/- 0.1/min, and spike burst conduction velocity was 4.7 +/- 0.3 cm/s. A complete migrating myoelectric complex was seen in 11 of 32 tracings (34%) and had a mean duration of 24.2 +/- 2.6 min. The ileal migrating action potential complex, most often seen in phase 2, had a frequency of 4.8 +/- 0.5 spike bursts/h and a conduction velocity of 13.6 +/- 0.4 cm/s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327616 TI - Hemodynamic responses of the equine digit to intravenous and digital arterial infusion of dopamine. AB - In 6 adult horses anesthetized with pentobarbital, the hemodynamic responses of the equine digit to infusion of dopamine were evaluated by use of an isolated extra corporeal pump perfused digital preparation. Digital blood flow was maintained at a constant rate that was independent of systemic hemodynamic changes. Three sequential experiments were performed on each horse. In the first experiment (n = 6), dopamine was infused IV at rates of 1.0, 2.5, and 5.0 micrograms/kg/min. For the second experiment (n = 5), dopamine (400 micrograms/ml) was infused into the digital artery at the rates of 0.07, 0.7, and 1.2 ml/min. The third experiment (n = 5) consisted of a 5-minute intra-arterial infusion of phentolamine followed by the intra-arterial infusion of dopamine while continuing the infusion of phentolamine. Digital venous, arterial, and capillary pressures, total digital vascular resistance, and precapillary to postcapillary resistance ratios were determined in each experiment. Systemic infusion of dopamine did not induce changes in the hemodynamics of the digital vasculature. Digital arterial infusion of dopamine alone resulted in a dose dependent increase in arterial pressure, total digital vascular resistance, and an increase in the precapillary to postcapillary resistance ratio. Phentolamine attenuated the vasoconstrictive response elicited by intra-arterial infusion of dopamine. PMID- 2327617 TI - Effect of meal feeding on plasma volume and urinary electrolyte clearance in ponies. AB - The effect of meal size and frequency on plasma volume, plasma aldosterone concentration and urinary Na and K clearances was determined in ponies. A daily maintenance ration of hay-grain pellets was provided either as a multiple feeding regimen, ie, 12 equal portions fed at 2-hour intervals, or as single large feedings, ie, half the ration fed every 12 hours at 0800 and 2000 hours. Only the effect of the single morning feeding was studied, using the latter regimen. Serial measurements of plasma volume were made by use of an indicator-dilution technique and indocyanine green (0.15 mg/kg of body weight, IV) that allowed repeated determinations at 2-hour intervals. Ingestion of the single large meal caused a 15% decrease in plasma volume by the end of a 1-hour feeding period. Feeding hypovolemia was confirmed by a coincident increase in plasma protein concentration (12%) and, in separate experiments, by analysis of postfeeding changes in the elimination of Evans blue dye. Plasma aldosterone concentration was significantly (P less than 0.05) increased from 2 to 5 hours after feeding. Urinary Na clearance decreased in response to feeding and remained lower than the prefeeding value until 9 hours after feeding. Urinary K clearance increased from prefeeding and reached a peak value between 5 and 7 hours after feeding. Creatinine clearance was unaffected. In contrast, the aforementioned variables were unchanged during the multiple regimen. Results indicate that ingestion of a large concentrate meal by ponies causes periprandial hypovolemia, activation of the renin-angiotensin-aldosterone system, and a subsequent antinatriuresis kaliuresis that lasts for several hours. PMID- 2327618 TI - High-performance liquid chromatography determination of erythrocyte membrane phospholipid composition in several animal species. AB - High-performance liquid chromatography (HPLC) was used to determine the phospholipid (PL) composition of ovine, equine, bovine, porcine, and canine RBC membranes. Procedural modifications of established techniques provided for separation of 7 PL within a 15- to 20-minute sample run. Significant (P less than 0.05) differences were detected in RBC membrane PL composition among the various species. The concern for physiologic properties associated with hemolysis and/or sedimentation rate must include evaluation of differences in the PL bilayer structure. PMID- 2327619 TI - Determination of excretion of inulin, creatinine, sodium sulfanilate, and phenolsulfonphthalein to assess renal function in goats. AB - Excretion of creatinine, sodium sulfanilate (SS), and phenolsulfonphthalein (PSP) was studied in healthy goats. In conscious goats, mean (+/- SEM) inulin clearance was 2.26 +/- 0.08 ml/min/kg of body weight. Endogenous creatinine clearance, 1.97 +/- 0.09 ml/min/kg, underestimated inulin clearance (P less than 0.01), probably because of the presence of noncreatinine chromogens in caprine plasma. The estimated renal clearance of PSP was 6.88 +/- 0.39 ml/min/kg, whereas the estimated renal clearance of SS was 3.71 +/- 0.39 ml/min/kg. Both exceeded inulin clearance (P less than 0.01), confirming renal tubular secretion of both compounds. In 6 anesthetized goats, exogenous creatinine clearance and SS clearance exceeded inulin clearance (P less than 0.05). Results of stop-flow experiments documented secretion of creatinine and SS by the proximal portion of the caprine nephron. Plasma half-life of PSP in uninephrectomized goats exceeded that in intact goats (20.2 +/- 1.5 min vs 11.9 +/- 0.7 min; P less than 0.01). Similarly, plasma half-life of SS was greater in goats after uninephrectomy (58.2 +/- 6.2 min vs 30.4 +/- 1.2 min; P less than 0.01). PMID- 2327620 TI - Glucose conservation by the kidney and effect of systemic glucose infusion on inulin clearance in female goats. AB - In 6 female goats, the mean threshold for glucosuria was 159.5 +/- 4.3 mg/dl. During increasing filtered loads of glucose, renal reabsorption of glucose reached maximal capacity, which was not exceeded when plasma glucose concentration was increased further. Measured in 10 female goats, the transport maximum for glucose was 119.1 +/- 9.1 mg of glucose reabsorbed/min. During infusion of glucose, there was a significant (P less than 0.05) time-dependent reduction in inulin clearance indicating that IV glucose administration may be inappropriate in goats with compromised renal function. PMID- 2327621 TI - Effect of age and training status on pharmacokinetics of flunixin meglumine in thoroughbreds. AB - The effect of age and training status on the pharmacokinetics of flunixin meglumine was evaluated in 16 Thoroughbreds. Horses were assigned to 1 of 3 groups on the basis of age and training status: group A (n = 6), horses in active training and less than or equal to 5 years old; group B (n = 5), horses out of training for a minimum of 6 weeks and less than or equal to 5 years old; and group C (n = 5), horses out of training for at least 2 years and greater than or equal to 9 years old. After administration of 500 mg of flunixin meglumine IV, multiple serum and urine samples were obtained over 24 hours and assayed for flunixin by high-performance liquid chromatography. Although the mean distribution rate constant and volume of distribution were similar for the 3 groups, mean total body clearance and elimination rate constant were significantly (P less than 0.05) greater and half-life significantly (P less than 0.01) less in groups A and B, compared with group C. Differences in pharmacokinetic values were not observed between the horses in group A and B. In addition, the changes in clearance, elimination rate constant, and half-life of flunixin were found to significantly (P less than 0.05) correlate with age. The results of this investigation indicated that age, but not training status, influences disposition of flunixin meglumine in Thoroughbreds. PMID- 2327622 TI - Potency of rapidly acting barbiturates in dogs, using inhibition of the laryngeal reflex as the end point. AB - Thiopental, thiamylal, and methohexital were administered to 30 dogs to determine equipotent doses necessary to inhibit laryngeal reflexes. The doses studied were 7.1, 10.0, 14.1, 20.0, and 28.3 mg of thiopental/kg of body weight; 5.7, 8.0, 11.3, 16.0, and 22.6 mg of thiamylal/kg; and 3.5, 5.0, 7.1, 10.0, and 14.1 mg of methohexital/kg. At 1, 2.5, 5, and 10 minutes after injection, the presence or absence of the laryngoscopic reflex, pedal reflex, and jaw tone were recorded. The times for return of each reflex, as well as the ability to walk 10 steps without assistance, were also recorded. Using the method of least squares, a probit analysis was performed on the quantal responses at 1 minute. The effective dose in 50% of the population for the laryngoscopic reflex was chosen as the end point for intubation, and the computed doses necessary to achieve this end point were 19.4 mg of thiopental/kg, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg. When potencies of the drugs were compared with that of thiopental (1), thiamylal was found to be equipotent (1.06) and methohexital twice as potent (2.0). At the accepted clinical dose, recovery times for thiopental (71.1 +/- 7.2 minutes) and thiamylal (75.3 +/- 7.7 minutes) were similar, and twice that for methohexital (33.9 +/- 4.6 minutes). PMID- 2327623 TI - Cardiovascular and respiratory effects of three rapidly acting barbiturates in dogs. AB - The cardiovascular and respiratory effects of 3 rapidly acting barbiturates, thiopental sodium, thiamylal sodium, and methohexital sodium, were studied in dogs from completion of injection until 12.5 minutes after injection. The doses administered were 19.4 mg of thiopental/kg of body weight, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg, which were chosen as equipotent doses necessary to inhibit the laryngoscopic reflex in 50% of the population. To determine the cardiovascular and respiratory effects for each drug, the values at each measurement time following injection were compared with baseline values (T0). At the 15- and 30-second measurement times following thiopental administration, stroke volume (SV) decreased; heart rate (HR), left atrial pressure, and mean pulmonary arterial pressure increased; and cardiac index (CI), myocardial contractility, and systemic and pulmonary vascular resistances were not different from baseline values. Mean arterial pressure (MAP) was not different from the baseline value at 15 seconds, but was increased from 30 seconds to 2 minutes. All values except HR had returned to baseline values by 7.5 minutes. At all measurement times, arterial oxygen tension and arterial pH were decreased, and arterial carbon dioxide tension increased from baseline values. Although the cardiovascular and respiratory changes following administration of thiamylal and methohexital were similar to those described for thiopental, some differences were found. Following thiamylal administration, systemic vascular resistance increased at 1 minute, pulmonary vascular resistance increased at 1 and 2 minutes, and myocardial contractility increased at 1 and 2 minutes. Following methohexital administration, MAP decreased at 15 seconds, and SV decreased at all measurement times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327624 TI - Influence of induced cholestasis on pharmacokinetics of digoxin and digitoxin in dogs. AB - Dogs with ligated common bile ducts were used to determine effects of cholestasis on pharmacokinetics of digoxin and digitoxin. Forty-three dogs were assigned to: group 1--sham-operated controls (n = 13); group 2--dogs with ligated common bile duct (n = 17); group 3--dogs given phenobarbital for 2 weeks before common bile duct was ligated (n = 11); or group 4--dogs with an induced biliary fistula (n = 2). Digoxin (group A) or digitoxin (group B) was given as single IV injections, and digitalis concentration in plasma was measured by radioimmunoassay. In 18 dogs given digoxin, differences in plasma digoxin concentrations among groups 1A to 3A were not significant (P greater than 0.1). Plasma elimination rate of digoxin was delayed in group 2A. Group-3A dogs had a shortened beta phase half life (t1/2 (beta] and a decreased distribution volume. In 25 dogs given digitoxin, group-2B dogs maintained a significantly higher plasma digitoxin concentration (P less than 0.01) and had a significantly longer t1/2 (beta] than did dogs in groups 1B and 3B (P less than 0.05). In group-3B dogs, plasma digitoxin concentration was decreased and t1/2 (beta] of digitoxin was shortened. In 10 group-B dogs given 3H-digitoxin (groups 1B, 2B, and 4B), the excretion of total radioactivity in urine and bile was 15 to 20 and 7% of the dose, respectively in the first 24 hours. Most radioactivity in urine and bile was a dichloromethane-unextractable fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327625 TI - Anatomy of the laryngeal and adjacent regions as perceived by palpation of clinically normal standing horses. AB - The anatomy of each feature and structure of the laryngeal and adjacent regions, as perceived by palpation, is described for clinically normal standing horses. Visible skin contours produced by some of the superficial structures are also described. Concurrent dissection was performed on fresh cadavers to confirm initial findings. The procedure of systematic palpation in relation to clinical diagnosis and surgical procedure is discussed. PMID- 2327626 TI - Evaluation of a commercial staphylococcal bacterin for management of idiopathic recurrent superficial pyoderma in dogs. AB - Twenty-one dogs with idiopathic superficial recurrent pyoderma were entered into a double-blind, placebo-controlled study to evaluate the efficacy of a commercial staphylococcal bacterin. The study spanned an 18-week period. All dogs were administered sodium oxacillin orally for the initial 6 weeks of the study. Dogs were given the bacterin or placebo SC, twice weekly at 3- or 4-day intervals, beginning at week 0 and continuing for 18 weeks. Dogs given antibiotics plus the bacterin (n = 13) had a significantly (P less than 0.05) better treatment response than those given antibiotic plus placebo. PMID- 2327627 TI - Immunoglobulin isotype of specific antibodies in reproductive tract secretions and sera in Tritrichomonas foetus-infected heifers. AB - Four virgin heifers were experimentally inoculated intravaginally with 7 x 10(6) Tritrichomonas foetus, and 2 heifers served as uninfected controls. The durations of infection were 13, 20, 21, and 28 weeks, respectively. An ELISA that used whole T foetus antigen was used to detect anti-T foetus immunoglobulins (IgA, IgG1, IgG2, and IgM) in vaginal, cervical, and uterine secretions, and sera during the course of infection. The vaginal and cervical antibody responses were characterized by significantly increased T foetus-specific IgA and IgG1 at 7 to 9 weeks of infection, whereas uterine IgA and IgG1 responses peaked at 10 to 12 weeks. The antibody response in serum was predominantly of the IgG1 and IgG2 subclasses. In all reproductive tract regions, IgA persisted at least until the time of T foetus clearance, and usually longer. The next most persistent isotype was IgG1, lasting longest in the vagina, then cervix, and for the shortest time in the uterus. In local secretions, IgG2 was seen only transiently, increasing at weeks 13 to 15 in the vagina, and at weeks 10 to 12 in the cervix. Little IgM, relative to that present before infection, was detected in any secretion or serum, although cervical secretions had the greatest amount. Eight to 12 weeks after clearance, the 4 experimental heifers were inoculated intravaginally with 1 x 10(5) T foetus; transient infections (2 to 3 weeks' duration) were established in only 2 of 4 heifers, as determined by culturing of reproductive tract secretions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327628 TI - Effects of repeated Strongylus vulgaris inoculations and concurrent ivermectin treatments on mesenteric arterial lesions in pony foals. AB - Eight of 10 pony foals reared under helminth-free conditions were inoculated PO with 50 Strongylus vulgaris infective larvae/week for 4 weeks, at which time 1 foal died of acute verminous arteritis. Inoculation of 7 remaining foals continued at 2-week intervals for 20 weeks. Of the 7 foals, 3 were treated with ivermectin (0.2 mg/kg of body weight) in an oral paste formulation at experiment weeks 8, 16, 24; 4 foals were not treated. Two foals were not inoculated or treated and served as controls. After the first ivermectin treatment, ivermectin treated foals had fewer days (12 +/- 2.9) with rectal temperatures greater than 38.6 C than did nontreated foals (23.3 +/- 3.8). Mean baseline rectal temperatures were 38 +/- 0.2 C. Adverse clinical reactions to ivermectin treatment were not observed in foals. Foals were euthanatized and necropsied 3 weeks after the last ivermectin treatment (week 24). Ivermectin was effective in reducing S vulgaris arterial larval and intestinal adult parasite numbers by 100% in 3 treated foals. Strongylus vulgaris arterial larvae and/or adults were recovered from all 4 nontreated inoculated foals. One nontreated inoculated foal lacked arterial larvae or active arterial lesions, indicating that protective resistance had developed in this individual. Marked gross and histopathologic lesions typical of chronic S vulgaris infection were observed in the 3 nontreated inoculated foals with arterial larvae. Repeated killing of intra-arterial S vulgaris fourth-stage larvae in ivermectin-treated foals did not exacerbate lesions associated with verminous arteritis or induce unique lesions associated with repeated destruction of arterial larvae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327630 TI - Use of mucosal grafts and temporary tube implants for treatment of teat sinus mucosal injuries. AB - A mucosal lesion was created in the center of each test sinus of 6 mature, healthy, nonlactating Holstein cows by resecting a circumferential band of mucosa. Each lesion was then treated by implantation of strip grafts of autogenous oral mucosa, temporary silastic tube implant, or a combination of strip grafts and temporary silastic tube implant. All teats were evaluated for patency 6 weeks after treatment, and tube implants were removed through a second thelotomy incision. All teats were reevaluated for gross and radiographic patency 12 weeks after treatment, and teats were collected for histologic evaluation of lesions. All 4 teats treated with grafts only were obstructed at 6 and 12 weeks after treatment. Incomplete coverage of the lesion with mucosa was observed in all 4 teats. The major source of obstruction was proliferation of epithelium and keratin into the lumen. All 8 teats treated with temporary silastic tube implants alone were patent at 6 weeks after treatment, but were obstructed at 12 weeks after treatment. Foci of mucosa at the lesion site were detected in only 2 of the 8 teats. Obstruction resulted from proliferation of granulation tissue into the lumen. All 12 teats treated with grafts and a temporary tube implant were patent at 6 weeks after treatment and 11 of 12 were patent at 12 weeks after treatment, although marked luminal narrowing was evident in 9 of 11 teats. Partial to complete coverage of the lesion with mucosa was seen in all teats. Proliferative granulation tissue, epithelium, and keratin contributed to luminal narrowing in 10 of 11 patent teats. Bacteriologic culture of quarters from 6 of the 11 teats patent at the final evaluation yielded pathogens. PMID- 2327629 TI - Sequential mesenteric arteriography in pony foals during repeated inoculations of Strongylus vulgaris and treatments with ivermectin. AB - Semiselective mesenteric arteriography was performed at regular intervals (inoculation weeks [IW] 0, 11, 18, and 24) in 9 of 10 pony foals raised to be free of parasites. Fifty infective larvae (L3) of Strongylus vulgaris were administered weekly for 4 weeks, then every 2 weeks through the 20th week. Three ponies were given ivermectin (oral paste, 0.2 mg/kg of body weight) treatment at IW 8, 16 and 24. Four ponies were inoculated, but did not receive ivermectin, and a third group of 2 ponies acted as uninoculated controls. Control ponies did not have gross or arteriographic lesions, whereas the inoculated untreated ponies had gross and progressive arteriographic lesions typical of verminous arteritis. Arteriographic lesions in the ivermectin-treated inoculated ponies were not as severe those in the untreated inoculated group, and there was either a partial resolution or a lack of progression of arteriographic lesions in all treated ponies. One untreated inoculated pony did not have progressive arterial lesions as did the 3 others in the group, and may develop resistance to the parasite. PMID- 2327631 TI - Study of long-term survival after transsphenoidal hypophysectomy in clinically normal dogs. AB - Experimental hypophysectomies were performed in 7 clinically normal dogs, using a new modification of the transsphenoidal approach. This approach facilitated centering of the sphenoid bone trephination and allowed safe exposure of the hypophysis regardless of the size or shape of a dog's skull. Complications did not occur during surgery and all dogs recovered well from surgery. Growth hormone secretory capacity was measured over a 3-month period to assess completeness of hypophysectomies. One dog was euthanatized 2 months after surgery, 4 dogs were euthanatized at 3 months after surgery, and 2 dogs were allowed to survive and their progress was followed for 2.5 years. Soft palate dehiscence and keratoconjunctivitis sicca developed in 2 of the dogs. The technical deficiencies responsible for these complications were corrected shortly after the beginning of the study. In 4 of the 5 necropsied dogs, minute remnants of adenohypophyseal tissue were found in the sellae turcica. Measurement of in vivo growth hormone secretory capacity revealed that these remnants had an altered stage of functional activity. Although complete hypophysectomy was not achieved consistently, the main technical obstacle of hypophysectomy, the reliable identification and the avoidance of the vascular structures surrounding the hypophysis, has seemingly been overcome. The surgical technique proved to enhance the safety of hypophysectomy, and the procedure can be recommended to treat clinical cases of canine pituitary-dependent hyperadrenocorticism. The clinical significance of potential subtotal hypophysectomy remains yet to be evaluated. PMID- 2327632 TI - An experimental model of chronic renal disease in dogs by infusion of microspheres into the renal arterial circulation. AB - The feasibility of renal arterial infusion of nonbiodegradable microspheres as a model of chronic renal disease in dogs was evaluated. Resin-coated, styrene divinyl benzene copolymer microspheres were infused into the kidneys of healthy adult Beagles by direct injections of both renal arteries in a single surgical procedure. Injections of 25-microns diameter microspheres had minimal effect on either the clinical status or serum values of the dogs. Histologic examination revealed the majority of the microspheres lodged within the capillary beds of the glomeruli, and little change to the kidneys. However, injections of 50-microns diameter microspheres caused significant increases in serum concentrations of urea nitrogen and creatinine. Histologically, the larger microspheres obstructed afferent arterioles and small arteries, which caused diffuse glomerular necrosis and nephron damage. With doses ranging from 1 to 3 million microspheres/dog, a correlation between the quantity of microspheres injected and severity of renal damage was observed. The optimal dose for producing a model of moderate renal disease was determined to be 1.8 million microspheres/dog (0.9 million microspheres/kidney). During long-term studies, microsphere-injected dogs fed a moderately restricted protein ration remained relatively azotemic, compared with control dogs on the identical ration. During the 5-month postsurgical period, the serum urea nitrogen concentration averaged 18.41 +/- 1.59 mg/dl (mean +/- SE) for the microsphere-injected dogs vs 9.31 +/- 0.38 for the control dogs (P less than 0.001). Similarly, the mean serum creatinine value was significantly higher (P = 0.020) for the microsphere-injected dogs, compared with the controls (1.23 +/- 0.12 mg/dl vs 0.94 +/- 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327633 TI - Gamma scintigraphic analysis of the distribution of perfusion of blood in the equine foot during black walnut (Juglans nigra)-induced laminitis. AB - Twelve horses, with acute laminitis (primarily in the forefeet) at 12 hours after intragastric dosing with an aqueous extract of black walnut (Juglans nigra) heart wood, were studied. The distribution of perfusion of blood to the foot and to outlined regions within the foot was quantified, using gamma scintigraphy of regionally infused 99mTc-labeled macroaggregated albumin, before and 12 hours after extract administration. Horses 1 to 3 were not studied further. Perfusion was quantified again for horses 4 to 12 at 84 hours after extract administration. At the onset of acute laminitis, horses 7 to 12 were administered a single dose of prazosin (0.025 mg/kg of body weight, IV) immediately after scintigraphy of the right forelimb and before scintigraphy of the left forelimb. When compared with baseline images, perfusion to the forefoot of horses after the development of acute laminitis was quantitatively decreased vs perfusion to the entire distal portion of the forelimb. Also with the onset of laminitis, perfusion also decreased to the dorsal laminar and coronary corium regions vs the distal portion of the forelimb. The acute laminitis-associated deficit in perfusion to the dorsal laminitis-associated deficit in perfusion deficit in perfusion to either the coronary corium or the entire forefoot. Equivalent deficits in the distribution of perfusion were not detected in forelimbs from horses with acute laminitis and which had been treated with prazosin. When compared with baseline images, perfusion to the dorsal lamina was increased in relation to perfusion to the distal portion of the limb at postdosing hour 84. Prazosin treatment did not influence that increase in perfusion to the dorsal lamina. PMID- 2327634 TI - Effects of aerosolized artificial surfactant on repeated oleic acid injury in sheep. AB - We studied the effects of an artificial surfactant, Exosurf, administered as an aerosol on respiratory system compliance (Crs), total respiratory resistance (RT), and gas exchange (PO2) in anesthetized, paralyzed sheep with oleic acid (OA)-induced lung injury. Paired experiments with OA were performed in 10 sheep, 5 of which received Exosurf in the first experiment and aerosolized 0.9% NaCl in the second; in the other 5 sheep the order of Exosurf and NaCl was reversed. Paired experiments without OA were performed in 6 additional sheep that served as controls. In the first set of experiments, OA caused significant abnormalities, compared to control and baseline values (p less than 0.02), in Crs, RT, and PO2; there was no difference between animals that received Exosurf and those that received NaCl. Baseline values for PO2 and Crs during the second set of experiments with OA were lower than controls (p less than 0.002), indicating that the animals had not fully recovered from their initial injury. After OA, the animals that received NaCl (i.e., the ones that received Exosurf the first time) had higher PO2 and Crs values (p less than 0.01) than those that received NaCl first and Exosurf second. There was no difference in postmortem lung water content between the animals that received Exosurf or NaCl first, both of which were higher than control (p less than 0.01). Studies in 3 additional sheep showed peripheral deposition of aerosol. Thus, we failed to show an acutely beneficial effect of aerosolized Exosurf in OA-induced lung injury; Exosurf did, however, appear to provide protection against some of the consequences of repeated lung injury. PMID- 2327636 TI - Single-breath carbon monoxide diffusing capacity prediction equations from a Mediterranean population. AB - Because of unanswered questions about prediction equations for the single-breath carbon monoxide diffusing capacity (DLCO) and as part of a larger collaborative project, standardized DLCO measurements were carried out in a selected sample of 361 healthy nonsmoking volunteers (194 men and 167 women) living in the Barcelona metropolitan area (Spain). Except for the test FIO2 (0.18), the study essentially followed the American Thoracic Society (ATS) and European Community for Coal and Steel (ECCS) recommendations for standardizing the methodology of measuring DLCO. Prediction equations for ages 20 through 70 were calculated separately for both sexes. Simple linear equations using age, height, and body weight as independent variables predicted the DLCO indices (DLCO, VA, and DL/VA) as well as more complex equations. In addition, a complete analysis of the residuals (predicted measured values) showed that the assumptions of the multiple regression analysis (independence, homoscedasticity and Gaussian distribution of residuals) were fulfilled using simple linear equations. Correction for the instrumental and anatomic dead spaces decreased the DLCO an average of 4.7%. The standard error of estimates was lower than those reported from other series in the literature. The predicted values from this study were lower than those reported by some investigators and were in reasonable agreement with other studies. A portion but not all of the differences could be explained on the basis of recognized differences in testing methodology. The results of this study may be of value to clinical laboratories seeking predictive equations for DLCO most appropriate for their testing methodology and patient population, and may assist in the resolution of some controversies regarding differences among predictive equations for DLCO. PMID- 2327635 TI - Extracellular matrix components in bronchoalveolar lavage fluid in sarcoidosis and their relationship to signs of alveolitis. AB - In lung sarcoidosis, the mutual relationships of three components of the extracellular matrix, fibronectin (FN), hyaluronan (HA), and type III procollagen peptide (PCP), were investigated in the bronchoalveolar lavage (BAL) fluid. Furthermore, their relation to signs of alveolitis and of fibrosis was examined. Sarcoidosis patients (n = 74) had significantly (p less than 0.001) increased BAL fluid concentrations of FN, HA, and PCP, as well as albumin and lymphocytes, compared to controls (n = 57). The increases were significantly higher in clinically active than in inactive sarcoidosis. FN, HA, and PCP were significantly correlated to markers of alveolitis, such as albumin (r approximately 0.6-0.7; p less than 0.001) and lymphocytes (r approximately 0.4 0.5; p less than 0.001 for FN and HA; p less than 0.05 for PCP), indicating that an alveolar inflammatory process may be a prerequisite for the increased production of the three components. Since correlations between FN and HA and functional parameters (VC, TLC, FEV1.0, and DLCO) were low (r approximately 0.2 0.3, p less than 0.05-0.01 for FN and HA), the increased levels of the extracellular markers do not seem to reflect developed fibrosis. The three markers of extracellular matrix showed significant (p less than 0.001) mutual correlations in the sarcoid patients (r approximately 0.7). FN and HA were correlated even in controls (r = 0.5; p less than 0.01). The findings are in agreement with our hypothesis that these compounds may participate in the buildup of an extracellular network that supports the healing process but in excess may eventually lead to fibrosis. PMID- 2327638 TI - Collection and analysis of respiratory mucus from subjects without lung disease. AB - We collected the respiratory mucus coating the endotracheal tubes used during short surgical procedures in 27 patients with no clinical evidence of respiratory disease. Twelve were male and 15 were female, and they ranged from 1 to 64 yr of age (mean, 28.7 yr). The viscoelastic properties, frog palate transport rate, and percent solid composition were in the normal range reported for both canine and human mucus collected using the bronchoscopy brush technique. There were no significant differences noted between male and female patients, and there were no changes in mucus or transport properties seen with aging. Mucus was also collected separately from the inside of the tube exposed to constant gas flow (13 patients), and from the outside of the endotracheal tubes in 25 patients. Although there were no significant differences in viscoelastic properties between inside and outside mucus, there was a greater thread formation (filance, 45 versus 26 mm; p less than 0.005) and a higher percentage of solids in mucus from the inside of the endotracheal tube (15.9 versus 11.4%; p less than 0.05), which is compatible with reduced hydration. The duration of anesthesia ranged from 25 to 195 min (mean, 85 min). There was no effect of duration of anesthesia on any of the measured mucus properties. This technique for mucus collection allows us to study alterations in mucus properties in patients with and without pulmonary disease at the time of incidental surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327637 TI - Carbon monoxide diffusing capacity, other indices of lung function, and respiratory symptoms in a general population sample. AB - To assess the relationships among single-breath diffusing capacity for CO (DLCOsb) (13), respiratory symptoms, and cigarette smoking in a general population sample, the data of 718 men and 894 women 20 yr of age or older were analyzed, and comparisons were performed with flow-volume curve (MEFV) variables and the slope of the alveolar plateau (DN2%/L) as well. Percent predicted DLCOsb and its correction for alveolar volume (DL/VA) were significantly lower in smokers than in nonsmokers. The relationship of presence/absence of respiratory symptoms and cigarette smoking with DLCOsb and DL/VA was significant. DLCO indices were almost always selected as discriminant variables in multivariate analysis between asymptomatic and symptomatic subjects. Poor concordance among lung function tests was evident: in men, 30% with abnormal (i.e., lower than 97.5% percentile) and 21% with normal DLCO indices also had abnormal MEFV parameters and/or DN2%/L. In women, the corresponding figures were 24 and 10%, respectively. In men, when considering only DLCO indices, the percentage of symptomatic subjects with abnormal lung function tests ranged from 33% in those with at least one symptom to 45% in those complaining of dyspnea. When the proportion of symptomatic subjects with DN2%/L and MEFV abnormalities were added, it increased to 56 and 66%, respectively. However, in women the proportion of symptomatic subjects with abnormal lung function indices was very small. These results indicate the usefulness of including CO diffusing capacity in epidemiologic surveys in the detection of abnormalities. PMID- 2327639 TI - Evaluation of the effect of localized skin cooling on nasal airway volume by acoustic rhinometry. AB - Ten healthy subjects (four men and six women) were subjected to localized skin cooling by submersion for 5 min of both feet and, in another experiment, one hand and forearm into ice-cold water. Repeated measurements of nasal cavity volumes by a new method, acoustic rhinometry, showed characteristic patterns ranging from marked increases in volumes lasting the entire exposure period to transient monophasic or biphasic responses to no change at all. The pattern in individual subjects was reproducible with the two methods of cooling, and it could be characterized by five types when related to baseline measurements during the preexposure period. Because of large minute-to-minute variations, probably determined by local differences and fluctuations in blood flow in tissues through the nose, evaluation of induced changes in the nasal cavity volume cannot be based on single measurements as has frequently been done in the past by using rhinomanometry as the experimental method. The mechanisms behind the characteristic patterns in immediate human nasal response to local skin cooling challenge remains to be explored. PMID- 2327640 TI - Intermediate antitrypsin deficiency. PMID- 2327641 TI - Presumptive diagnosis and treatment of pulmonary tuberculosis based on radiographic findings. PMID- 2327642 TI - Prognostic implications of bronchoalveolar lavage neutrophilia in patients with Pneumocystis carinii pneumonia and AIDS: effects of an aggressive therapeutic approach. PMID- 2327643 TI - Twenty isoniazid-associated deaths in one state. PMID- 2327644 TI - Tuberculin test, preventive therapy, and elimination of tuberculosis. PMID- 2327645 TI - Choosing an appropriate criterion for true or false conversion in serial tuberculin testing. AB - This study evaluates five different criteria of true conversion in relation to the annual tuberculosis infection rate or risk of infection. It also examines prospective results of a general population, 16 to 69 yr of age, who had less than 6 mm of induration at first PPD test. This population received a second PPD test between 1976 and 1986. In about 95% of cases, the interval was 1 to 5 yr. In 1,355 bacillus Calmette-Guerin (BCG)-vaccinated subjects, none of the criteria is acceptable for true conversion. Among 1,834 nonvaccinated BCG, only the criterion of a change from less than 10 to 18 mm or more with an increase of 12 mm or more, or the criterion of change from less than 10 to 18 mm or more with an increase of 18 mm or more, is compatible with true conversion and with the correspondent annual risk of infection. But we must accept that with smaller increases, recently infected persons may escape diagnosis of infection. A third test was performed in 81 subjects with two negative test results. In all cases except one, the annual conversion rate observed was much higher than the annual risk of infection. These data reveal shortcomings of the current criterion for conversion. They show that the tuberculin conversion at retesting is not epidemiologically related to new infection and that none of the criteria assures the discovery of true converters. Other factors must be taken into account. PMID- 2327646 TI - Alveolar targeting of aerosol pentamidine. Toward a rational delivery system. AB - Nebulizer systems that deposit a high proportion of aerosolized pentamidine on large airways are likely to be associated with marked adverse side effects, which may lead to premature cessation of treatment. We have measured alveolar deposition and large airway-related side effects (e.g., cough, breathlessness, and effect on pulmonary function) after aerosolization of 150 mg pentamidine isethionate labeled with 99mTc-Sn-colloid. Nine patients with AIDS were studied using three nebulizer systems producing different droplet size profiles: the Acorn System 22, Respirgard II, and Respirgard II with the inspiratory baffle removed. Alveolar deposition was greatest and side effects least with the nebulizer producing the smallest droplet size profile (Respirgard II), whereas large airway-related side effects were prominent and alveolar deposition lowest with the nebulizer producing the largest droplet size (Acorn System 22). Values for alveolar deposition and adverse airway effects were intermediate using the Respirgard with inspiratory baffle removed, thus indicating the importance of the baffle valve in determining droplet size. Addition of a similar baffle valve to the Acorn System 22 produced a marked improvement in droplet size profile. Selection of a nebulizer that produces an optimal droplet size range offers the advantage of enhancing alveolar targeting of aerosolized pentamidine while reducing large airway-related side effects. PMID- 2327647 TI - Collagen synthesis during lung development and during hyaline membrane disease in the nonhuman primate. AB - To assess maturational changes in collagen synthesis, lung tissue was obtained from healthy Macaca nemestrina monkeys at different ages, ranging from 68% of term gestation to adulthood. We hypothesized that infants delivered prematurely have a greater rate of collagen synthesis than do older animals because of their greater rate of lung growth during gestation. Secondly, we hypothesized that lung repair in infants with hyaline membrane disease (HMD) is associated with an additional increase in lung collagen synthesis rate. Therefore, lung tissue was obtained during the first week of life from monkeys delivered at 82% of term gestation, a stage at which half of them developed HMD. The rate of total protein synthesis in lung samples was determined by measuring the incorporation of [3H]proline; the rate of collagen synthesis was determined by measuring the conversion of proline into hydroxyproline. Premature monkeys had a higher rate of collagen synthesis (9.9 +/- 2.7 nmol/mg DNA/h) than did term infants (5.3 +/- 1.1) or older animals (2.1 +/- 0.4, p less than 0.05). There was no additional increase in rate of collagen synthesis in animals with HMD from 3 h (14.3 +/- 6.9) to 7 days of age (15.1 +/- 6.1); control premature animals also had no significant change during the first week of life (10.9 +/- 3.0 at 3 h; 11.6 +/- 4.6 at 7 days). The early stage of recovery from HMD in premature monkeys does not appear to be associated with an increase in collagen production beyond the already increased synthesis rate associated with lung growth. PMID- 2327648 TI - Effect of lung inflation on pulmonary resistance during NREM sleep. AB - Previous investigations have demonstrated an inverse relationship between lung volume and airway resistance in awake humans. We wished to examine this relationship in the absence of conscious influences. We therefore studied eight healthy subjects who slept in a tank respirator. Hyperinflation was induced by continuous negative tank pressure while the subjects breathed spontaneously. Ventilation, pulmonary resistance (total pulmonary resistance, seven subjects; upper airway resistance, one subject), diaphragm and genioglossus electromyograms (EMGs), and sleep state were measured. During control NREM sleep, group mean maximal pulmonary resistance was 42.5 cm H2O/L/s (range, 17.4 to 106.4 cm H2O/L/s). During steady-state hyperinflation (mean increase in lung volume = 0.53 L), pulmonary resistance decreased 40% (range, -3 to -90%). Ventilation, sleep state, and end-tidal CO2 were unchanged. Inspiratory muscle EMG was increased in two of two subjects during hyperinflation. Genioglossus EMG was characterized by phasic and tonic activity during the control period in two of two subjects. Both components were decreased during steady-state hyperinflation. When lung volume was returned to baseline, pulmonary resistance and genioglossus EMG increased to baseline levels. We conclude that alteration in lung volume within the tidal volume range significantly alters pulmonary resistance during NREM sleep. This influence occurs independent of chemical stimuli or genioglossal muscle activity, and may be related to traction on neck structures caused by descent of mediastinal structures. PMID- 2327649 TI - Cheyne-Stokes respiration presenting as sleep apnea syndrome. Clinical and polysomnographic features. AB - This study reports polysomnographic features of five patients with Cheyne-Stokes respiration (CSR). They were referred for evaluation of presumptive sleep apnea syndrome on the basis of history and physical examination, but were found to have predominantly CSR on all-night sleep study. On the initial polysomnographic study, CSR comprised 47 to 86% of all disordered-breathing events. Cheyne-Stokes respiration resulted in considerable oxyhemoglobin desaturation (mean baseline saturation was 95 +/- 4 +/- SD, and lowest saturation was 76 +/- 8). More than one-half of all CSR events resulted in awakenings or arousals. Evidence of upper airway obstruction was noted in the majority of CSR events in three of five patients. Four patients were treated with theophylline; one who refused drug therapy was treated with nasal continuous positive airway pressure (CPAP). Comparison of sleep studies before and after therapy showed a significant decrease in the CSR index (29 +/- 11 versus 2 +/- 2) and in the maximal oxyhemoglobin desaturation associated with CSR (13 +/- 5 versus 3 +/- 2), and an improvement in lowest O2 saturation associated with CSR (76 +/- 8 versus 91 +/- 4). Total disruptions in sleep architecture per hour of sleep improved significantly with therapy (46 +/- 21 versus 20 +/- 8). We conclude that the clinical presentation of CSR can be indistinguishable from that of the "traditional" sleep apnea hypopnea syndrome and can result in major oxyhemoglobin desaturation and sleep fragmentation. Theophylline results in considerable improvement in the disordered breathing of CSR during sleep. PMID- 2327650 TI - The antielastase screen of the lower respiratory tract of alpha 1-proteinase inhibitor-sufficient patients with emphysema or pneumothorax. AB - The present study was aimed at testing whether alpha 1-proteinase inhibitor sufficient patients with lung emphysema or idiopathic spontaneous pneumothorax have an impaired antielastase protection at the lung alveolar level. We have collected bronchoalveolar lavage fluids (BALF) from 20 PIMM emphysematous patients (44 +/- 12 yr), 24 patients with pneumothorax but no radiologic evidence of emphysema (30 +/- 11 yr), 32 healthy subjects (27 +/- 6 yr), and 56 patients with sarcoidosis (30 +/- 11 yr). The BALF were assayed for immunoreactive albumin, alpha 1-proteinase inhibitor (alpha 1PI), leukocyte elastase-alpha 1PI complex (LE-alpha 1PI), and mucus proteinase inhibitor (MPI) as well as for porcine pancreatic elastase inhibitory capacity, a measure of active alpha 1PI. The healthy subjects and the patients with emphysema or pneumothorax had comparable levels of total and active alpha 1PI and total MPI. In contrast, the levels of LE-alpha 1PI complex were elevenfold higher in patients with emphysema than in normal subjects (p = 0.021) and tended to increase with the severity of the disease because they were negatively correlated with FEV1/FVC% (r = -0.55; 0.05 less than p less than 0.1). They did not vary with age in a population of patients with sarcoidosis (r = 0.03), suggesting that their eleven-fold increase in emphysematous patients is not related to the age of these subjects. Patients with pneumothorax had levels of LE-alpha 1PI complex that did not significantly differ from those of normal subjects (p = 0.24).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327651 TI - Pulmonary function in middle-aged women with heterozygous deficiency of the serine protease inhibitor alpha 1-antichymotrypsin. AB - Heterozygous alpha 1-antichymotrypsin (ACT) deficiency is inherited in an autosomal dominant mode independently of alpha 1-antitrypsin with a gene frequency (q) of 0.003. In a previous study, a high prevalence of enlarged residual volumes in subjects with the trait were noted. Neutrophil cathepsin G, the target proteinase of ACT, enhances the elastolytic action of elastase. Thus, hypothetically, subjects with the trait may have increased risk for developing pulmonary emphysema. To test whether heterozygous ACT deficiency predisposes to lung disease, plasma ACT concentrations were determined in a cohort of 1,872 middle-aged women. Women with subnormal levels were studied with respect to heredity, airway symptoms, and lung function. Twelve women (0.64% of the cohort) were classified as heterozygotes after family studies and were compared with control subjects, matched for age, weight, sex, and smoking status. There were no significant differences in airway symptoms between heterozygotes and control subjects. However, the prevalence of ex-smokers was significantly higher among heterozygotes than among the screened population as a whole (prevalence ratio, 2.18; 95% confidence interval, 1.004-4.72). There were no differences between the heterozygotes and the control subjects in the basal spirometry. However, after bronchodilation, five of the 12 heterozygotes manifested residual volumes greater than 2.5 standard deviations above normal mean compared with one of 24 control subjects (p = 0.012). The present investigation thus confirms our previous findings of an increased prevalence of enlarged residual volumes in heterozygous ACT deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327652 TI - Pharmacokinetics and distribution of recombinant secretory leukocyte proteinase inhibitor in rats. AB - Secretory leukocyte proteinase inhibitor (SLPI) is a potent elastase, trypsin, and chymotrypsin inhibitor occurring in all mucous secretions. Its inhibitory potency and profile suggested that it may become a therapeutic adjuvant in diseases where proteinases play a pathogenetic role. In the course of developing recombinant SLPI for therapeutic purposes, we studied its pharmacokinetics after intravenous, intraperitoneal, and intratracheal application to rats. In plasma, SLPI was determined with an ELISA or by following a radiotracer [( 35S]SLPI). In bronchoalveolar lavage fluid (BALF), SLPI was determined additionally by a functional assay (elastase inhibitory capacity). Intravenously applied SLPI (2 mg/kg) was rapidly cleared, with half-times of distribution of 6 min and half times of elimination of 50 min. Very little (less than 5%) appeared in the urine even after 24 h. Approximately 80% of intraperitoneally injected SLPI (12 mg/kg) was absorbed and generated maximal plasma concentration of 6 to 10 micrograms/ml 30 to 120 min after administration. When given intratracheally (8.6 mg/kg), SLPI disappeared from the lungs, with a half-time of 4 to 5 h. This value was the same whether the remaining SLPI in BALF was determined radiometrically, by ELISA or by the functional assay, indicating minimal metabolism in the lung. As in the case of intraperitoneal application, SLPI was absorbed systemically, resulting in a maximal plasma level of about 2 micrograms/ml 1 to 2 h after application. In contrast to the measurements in BALF, the ELISA and radiotracer measurements in plasma correlated only for the first 2 h after application and diverged progressively after that, suggesting breakdown of the molecule once it reaches the plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327653 TI - Lung structure and gas exchange in mild chronic obstructive pulmonary disease. AB - To investigate the influence of pulmonary emphysema and small airways abnormalities on ventilation-perfusion (VA/Q) mismatching in mild chronic obstructive pulmonary disease (COPD), we studied 23 patients (mean predicted FEV1, 76 +/- 15%) before lung resection because of a localized neoplasm. Respiratory gas exchange and VA/Q distributions were measured while the patients breathed room air and 100% O2. Breathing room air, the AaPO2 was moderately increased (25 +/- 12 mm Hg) as was VA/Q mismatching, indicated by the dispersion (log SD) of both blood flow (Q) and ventilation (V) distributions (log SD Q, 0.78 +/- 0.3; and log SD V, 0.66 +/- 0.28, respectively) (normal range, 0.3-0.6). AaPO2, log SD Q, and log SD V all significantly correlated with the emphysema severity assessed morphologically from the resected lung specimens (r = 0.57, r = 0.62, and r = 0.45, respectively). Log SD V also significantly correlated with the severity of the inflammatory infiltrate of membranous bronchioles (r = 0.62). During 100% O2 breathing there was an increase in VA/Q mismatching (log SD Q rose to 1.12 +/- 0.08, p less than 0.001), suggesting release of hypoxic pulmonary vasoconstriction. This increase in VA/Q inequality was not significantly related to the severity of lung pathologic findings. We conclude that, in mild COPD, both pulmonary emphysema and small airways abnormalities contribute to VA/Q mismatch, the severity of emphysema being the major morphologic correlate of the increase in AaPO2. PMID- 2327654 TI - The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels. AB - Advanced emphysema with bronchitis is associated with significant weight loss and malnutrition, the true cause of which has not been clearly identified. The purpose of this exploratory study was to compare plasma amino acids and related compounds and catecholamines in a group of patients with advanced end-stage emphysema with a control group of similar age and sex in an effort to further understand this malnourished state. Fasting blood samples were obtained by venipuncture after a rest period. Plasma amino acid levels were determined by ion exchange high pressure liquid chromatography with fluorometric detection. Plasma catecholamines were determined by radioenzymatic analysis. Anthropometric measurements, the usually accepted biochemical markers of nutrition, dietary analysis, pulmonary function tests, and a historical analysis of the state of health including drug use and smoking history in each subject were analyzed. Ages and heights were comparable, whereas weights were significantly decreased in the patients with emphysema. Total serum protein and serum albumin values were significantly lower in the patient group. Significant respiratory muscle weakness was indicated by reduced negative inspiratory force in these end-stage patients, contrasting with well-preserved muscle strength usually found in obstructive lung disease. The dietary caloric intake of the patients was comparable to that of the control subjects. We conclude that the fine balance of the amino acid pool in patients with bronchitis and emphysema is well preserved, except for significant elevations of aspartic acid, glutamine, and cystine, and a decreased level of leucine. In addition, norepinephrine levels were significantly increased. Weight loss in patients with emphysema and bronchitis is likely due to increased energy demands related to hypermetabolism. PMID- 2327656 TI - The mechanism of respiratory arrest in inspiratory loading and hypoxemia. AB - Respiratory arrests occur in the clinical setting of respiratory failure, but the mechanism is unclear. We used a dog model with increased inspiratory resistance and hypoxemia to explore the cause. We hypothesized that respiratory muscle fatigue (RMF) played a role in these respiratory arrests, and that the combination of hypoxia and resistive loading would produce respiratory arrest by the mechanism of RMF. Our preparation had transdiaphragmatic pressures that were 40% of maximum (Pdimax = 46.3 +/- 10.0 cm H2O) and progressive hypoxia resulting in a final arterial PO2 of 38 +/- 9 mm Hg and a phrenic vein O2 content of 1.8 +/ 1.1 mg/dl. Instead of failure associated with carbon dioxide retention and RMF, we saw a rapid decrease in tidal volume and respiratory rate, leading to apnea over 30 to 60 s while the diaphragm still responded with significant pressure generation when externally stimulated. These results suggest that respiratory muscle fatigue may not be a major factor in respiratory arrests associated with inspiratory loading and hypoxia, but that suppression of central drive, induced by the combination of inspiratory loading and hypoxemia, may be important. PMID- 2327655 TI - Comparison of scales used to quantitate the sense of effort to breathe in patients with chronic obstructive pulmonary disease. AB - Several different scaling techniques, i.e., Borg category (BC) and visual analogue (VA) scales have been used to quantitate the intensity of the respiratory sensations elicited during exercise, but their relationship is unclear. Six subjects with stable chronic obstructive lung disease (FEV1 = 1.2 +/ 0.1 SE L) simultaneously rated the sense of effort to breathe with both BC and VA scales during progressive, maximal exercise tests performed three to five times on a cycle ergometer. The VA scores correlated linearly with minute ventilation in all subjects in all trials (r = 0.98 +/- 0.01), and when converted to common units (i.e., Z scores) correlated closely with simultaneous scores obtained using the Borg scale (r = 0.99 +/- 0.01). Furthermore, VA scores varied minimally over several trials. Coefficient of variation for the maximal VA scores was 6 +/- 1%, which was similar to the variation in maximal Borg score (i.e., 3 +/- 1%). We conclude that the visual analogue scale is reproducible and correlates closely with the Borg score when scaling the sense of effort to breathe during exercise in subjects with stable chronic obstructive pulmonary disease. PMID- 2327657 TI - Neutrophil kinetics in the pulmonary microcirculation. Effects of pressure and flow in the dependent lung. AB - Increases in pulmonary arterial pressure or blood flow raise peripheral white cell count by releasing sequestered leukocytes from the lung. The effects of altered hemodynamics, however, on the leukocyte sequestration site and on the distribution of leukocyte transit times through the pulmonary microcirculation are unknown. We used in vivo fluorescence videomicroscopy to study the passage of individual, fluorescein-isothiocyanate-labeled neutrophils through the pulmonary microcirculation of anesthetized dogs. Pulmonary hemodynamics were altered over a wide range. Regardless of the hemodynamic conditions, the only place that any of the 2,919 observed neutrophils stopped was in the capillaries. The periods of immobility had a wide range, from less than 1 to greater than 1,200 s. Because the cells remained motionless once they stopped and then accelerated suddenly as they regained the free-flowing stream, the obstructions must have been discrete. About a quarter of the capillary pathways had one site of high resistance. Another quarter offered two or more obstructions. In the remaining half, the neutrophils passed rapidly and without pause from arteriole to venule. Increases in pressure and flow decreased the number of times that individual cells stopped. These changes altered the median transit time by shifting the distribution of transit times between the slowest and fastest groups. We conclude that most of the total pathlength of perfused capillaries offers little resistance even to neutrophils. There are, however, focal areas in individual capillaries that offer high resistance to neutrophil passage. PMID- 2327659 TI - Changes in surfactant in bronchoalveolar lavage fluid after hemithorax irradiation in patients with mesothelioma. AB - Experimental studies have shown that the surfactant system of the lung is affected shortly after irradiation. It is unclear, however, whether surfactant plays a role in the pathogenesis of radiation pneumonitis. In the present study surfactant components (saturated phosphatidylcholine, surfactant protein A, phosphatidylglycerol, and phosphatidylinositol) and other phospholipids of bronchoalveolar lavage fluid (BAL) were studied in four patients with pleural mesothelioma before and during hemithorax irradiation (70 Gy) as well as zero, 1, 2, 3, and 4 months following irradiation. The concentrations of these same components and of soluble proteins were also estimated in the epithelial lining fluid (ELF) using urea as a marker of dilution. After radiotherapy, the concentrations of the surfactant components in ELF decreased to 12 to 55% of the control values before radiation, whereas the concentration of sphingomyelin in ELF increased ninefold. There were small changes in the other phospholipids. The concentration of soluble protein in ELF increased sevenfold. The minimum surface activity of crude BAL increased from 12 +/- 4 to 32 +/- 6 mN/m, and that of the sediment fraction of BAL increased from 7 +/- 4 to 22 +/- 6 mN/m, p less than 0.001. The protein-rich supernatant fraction of BAL from irradiated lung had a inhibitory effect on normal surfactant. There were significant correlations between the increasing severity of the radiologic changes on the one hand and, on the other, the saturated phosphatidylcholine/sphingomyelin ratio (p less than 0.001), the concentrations of soluble protein (p less than 0.001), and the concentrations of the surfactant components (p less than 0.02-0.001) in ELF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327658 TI - Regulatory effect of prostaglandin E2 on fibronectin release from human alveolar macrophages. AB - Fibronectin (Fn), which is released from several kinds of cells including alveolar macrophages (AM), is important in inflammatory reactions in the certain lung diseases such as idiopathic pulmonary fibrosis (IPF). Therefore, information on the mechanisms regulating Fn release from AM may be useful for elucidating the pathogenesis of these diseases and developing therapeutic modalities. We supposed that prostaglandin E2 (PGE2), which is known to modulate cellular functions, might be involved in regulation of Fn release, and, accordingly, we measured the release of Fn and PGE2 from AM from normal volunteers (NV), control patients (CP), and patients with IPF. AM from patients with IPF were found to release more Fn than AM from NV (IPF: 250 +/- 58.8/10(6) cells.24 h, NV: 53.0 +/- 7.3 ng/10(6) cells.24 h) and to release less PGE2 than the latter (IPF: 0.48 +/- 0.12 ng/10(6) cells.24 h, NV:1.35 +/- 0.24 ng/10(6) cells.24 h). A negative correlation was found between the contents of Fn and PGE2 in the culture media of AM from NV, CP, and patients with IPF. Lipopolysaccharide, phorbol myristate acetate, and zymosan suppressed Fn release from AM but stimulated their PGE2 release, and these effects were reversed by indomethacin. Exogenous PGE2 (greater than 1 x 10(-8) M) suppressed Fn release. The albumin-antialbumin complex stimulated Fn release but did not affect PGE2 release. These results indicate that Fn release from AM changed in response to various stimuli, and that PGE2 is important in suppressing Fn release from AM, suggesting a negative feedback mechanism of PGE2 in releasing Fn. PMID- 2327660 TI - [Enhancing factors in the cardiotoxicity of anthracyclines]. AB - We have studied 60 pediatric patients with different neoplastic diseases, treated with anthracyclines. We have followed them clinically and echocardiographically to detect the cardiotoxicity due to anthracyclines and the enhanced factors promptly. We have detected a more important incidence of cardiomyopathy in patients with non-Hodgkin's lymphoma, osteosarcoma and neuroblastoma despite cumulative doses under 550 mg/m2 of anthracyclines. The 2 first groups were treated with high doses of cyclophosphamide and methotrexate, and neuroblastomas with melphalan. The anthracyclines cardiotoxicity is evaluated around 5% in patients treated with doses under 550 mg/m2, and is increased in case of previous or simultaneous aggressive therapy. Continued echocardiography enables a premature detection of cardiotoxicity in these high risk patients. PMID- 2327661 TI - [Long-term follow up of children with transposition of great vessels with intact interventricular septum]. AB - From January 1971 to January 1988, 140 patients were diagnosed of complete transposition of the great arteries with an intact ventricular septum. These patients are the 6% of the 2,322 children diagnosed of congenital heart disease by catheterization and angiography in this 17 year period. The overall mortality was 63.5%. Sixty children died at a mean age of 55 days before cardiac surgery was performed, mostly before 1982. Forty nine patients underwent a Senning procedure with a surgical mortality of 30.6%. Between 1983 and 1988, with the use of infusion of prostaglandin E in the neonatal period, 28 children underwent a Senning procedure at a mean age of 12 months with a surgical mortality of 17.8%, and an actuarial survival rate of 80.9%. At late examination the 55.8% of the survivors were asymptomatic and the 8.8% showed caval or pulmonary venous obstruction. PMID- 2327662 TI - [Mortality and survival rate in pulmonary atresia with intact intraventricular septum. Determining factors]. AB - Sixty nine children with pulmonary atresia and intact ventricular septum diagnosed by catheterization from 1971 to 1988 are reviewed. These patients are the 2.9% of the 2,322 children diagnosed of congenital heart disease by catheterization and angiography in this 17 year period. The overall mortality was 72.4%. Twenty children died at a mean age of 37 days before cardiac surgery was performed, mostly before 1982, before the use of prostaglandin infusion. Forty seven children received surgical treatment, with a surgical mortality rate of 74% at the period 1971-1982 and 54% at the period 1983-1988. The right ventricular hypoplasia was the anatomic factor of dismal outlook. The actuarial survival in the patients without hypoplastic right ventricle and surgical treatment was 52% in the period 1971-1988 and near 80% in the first 3 years of life in the period 1983-1988. The use of preoperative prostaglandin infusion and improved operative techniques has changed the natural history of this malformation. PMID- 2327663 TI - [Normal and impaired development of the ostium primum type atrial septal defect]. AB - We evaluate 48 patients who had catheterization-proved atrial septal defect ostium primum type. These patients are the 2% of the 2,322 children diagnosed of congenital heart disease by catheterization and angiography in our hospital at the 1971-1988 period. Of 48 children, 36 underwent corrective surgical repair at mean age of 6 years, with a surgical mortality rate of 11.1%. Our mortality rate total was 12.5% and the average follow-up was 9 years. The most recent evaluation in the 32 survivors of complete repair shows that 2 children had complete atrioventricular block and pacemaker implanted, and 26 children had residual mild to moderate mitral regurgitation. Two children are in the functional New York Heart Association class III and 24 children in the class I or II. The estimated actuarial survival rate at the 10-15 years is 86.3% in the total and 88.2% in the operated group. PMID- 2327664 TI - [Use of objective structured clinical examinations in the pre-graduation evaluation of medical students in pediatrics]. AB - The present article deals, firstly with the analysis of the classic evaluation procedures for assessing the pregraduate medical students employed in our University, and their negative influence upon the results obtained in the studying procedures as well as in the degree of acquaintance. A new model, previously assayed in other universities and named objective structured clinical examination, which combines the assessing of the theoretical and practical knowledge, is proposed. Its peculiarities are explained, as well as its advantages and disadvantages; we also suggest the way of starting its application considering the features of the educational system ruling our University. PMID- 2327665 TI - [Amoxicillin in association with clavulanic acid in the treatment of urinary infection in children]. AB - Fifty-eight paediatric patients aged one month to 14 years, who met the inclusion criteria for urinary infection, were studied. They were administered amox/clav at a dose of 21.9 +/- 2.96 (mean +/- SD) mg/kg/day for ten days. E. coli was isolated in 53 cases, P. mirabilis in two, K. pneumoniae in two and E. cloacae in one. Of the E. coli, 94.34% were sensitive to amox/clav, 67.92% were resistant to ampicillin, three cases showed intermediate sensitivity and the case of E. cloacae was resistant. These four patients were withdrawn from the study, and four more who did not come for follow-up. Of the 50 assessable patients, 94% were cured. Three days after completing the treatment, three patients (6%) still had a positive uroculture, although only one showed symptoms. Of the remaining 47, five cases (11%) presented bacteriological relapse in the culture made seven days later. Only 10% of the patients showed any type of gastrointestinal disturbances, and interruption of treatment was not necessary. The amox/clav combination, in view of its broad spectrum, easy administration by oral route and good tolerance, should be taken into account as a first choice treatment in urinary infections in paediatric patients of any age. PMID- 2327666 TI - [Acute lymphoblastic leukemia: clinical data and results of intensive chemotherapy]. AB - Twenty-one children, between eight months and twelve years old, diagnosed as having acute nonlymphoblastic leukemia (ANLL), were treated with an intensive chemotherapy based on a modified VAPA protocol. Complete remission rate was 80%, and the 5 year-survival rate is 46%. One chloroma, one central nervous system, and four bone marrow relapses were observed; all except the first having an unfavourable outcome. Significant risk prognostic factors in this series proved to be hepatomegaly (greater than 5 cm) and delay in obtaining remission. No fatal complications were observed. PMID- 2327667 TI - [Poisoning by Robinia pseudoacacia]. AB - We present a 7 boys Robinia pseudoacacia (black locust) intoxication. Three of them showed neurological symptoms, including coma. All of them showed gastrointestinal symptomatology. Evolution was satisfactory in all of them. A bibliographic revision is done. PMID- 2327668 TI - [Severe infection caused by Candida parapsilosis in an infant]. AB - Three cases of serious infections due to Candida parapsilosis in infants are reported. Two patients are children exposed to abdominal surgery, parenteral nutrition and antibiotic treatment, who developed catheter-associated sepsis with successful response to change of catheter and intravenous amphotericin B, despite one of the patients showed a relapse some weeks after. Third patient, a hydrocephalic child with external ventricular shunt, developed cerebrospinal fluid infection without response to antifungal treatment and died. Sepsis and meningitis due to Candida parapsilosis can be observed in infants with some risk factors, as use of intravascular or intraventricular catheters. Change of the catheter and treatment with amphotericin B are indicated in these infections. PMID- 2327669 TI - [Protein-losing enteropathy of cardiac origin: value of intestinal clearance of alpha-1-antitrypsin]. AB - Two patients with protein-losing enteropathy of cardiac origin, one case due to constrictive pericarditis and another as a complication of a Fontan operation, are presented. In both cases the clinical symptomatology and the analytical pattern were very suggestive of loss of protein through the intestinal lumen. This was confirmed by the determination of fecal fecal alpha-1-antitrypsin (alpha 1-AT) and its intestinal clearance. The utility of both determinations as a simple and secure method in substitution of isotopic studies is emphasized. PMID- 2327670 TI - [Schonlein-Henoch purpura and IgA nephropathy. A common pathogenetic cause?]. PMID- 2327671 TI - [Atrophic panniculitis of connective tissue. Report of a case]. PMID- 2327672 TI - [Neurologic manifestations of HIV infection in an infant]. PMID- 2327673 TI - [Arteriovenous malformation in the vermis: apropos of a case]. PMID- 2327674 TI - Gender, coronary artery disease, and coronary bypass surgery. PMID- 2327675 TI - Adverse effects of nonsteroidal anti-inflammatory drugs on renal function. PMID- 2327676 TI - Increased mortality of women in coronary artery bypass surgery: evidence for referral bias. AB - STUDY OBJECTIVE: To determine whether differences in referral reasons explain the higher operative mortality of women in coronary artery bypass surgery. DESIGN: Case series. SETTING: A tertiary care, private teaching hospital. PATIENTS: Consecutive patients who had isolated coronary artery bypass surgery between 1982 and 1987 (total, 2297; 79% male and 21% female). MEASUREMENTS AND MAIN RESULTS: The inhospital mortality rate was significantly higher for women than for men (4.6% compared with 2.6%; P = 0.036; 95% CI for difference in mortality, 0% to 4.0%). Women were older than men (mean, 68.2 and 64.0 years, respectively; P less than 0.001), and a higher percentage of women were referred with unstable angina (P = 0.007), postmyocardial infarction angina (P = 0.029), congestive heart failure (P less than 0.001), and New York Heart Association class IV symptoms (66% compared with 45%, P less than 0.001). More men were referred with a history of an abnormal exercise test (P less than 0.001), and patients referred because of a positive exercise test had a lower mortality (P less than 0.001). Using multivariate analysis, adjustment for the higher preoperative functional class of women and for age accounted for all of the difference in mortality between men and women (odds ratio, 1.04; CI, 0.60 to 1.79; P = 0.89). After correction for functional class alone, there continued to be no significant difference in mortality between men and women (P = 0.40). CONCLUSIONS: Differences in functional class and age account for the higher operative mortality of women in coronary bypass surgery. Women are referred for coronary bypass surgery later in the course of their disease than men, and later referral may increase their changes of operative death. PMID- 2327677 TI - Long-term methotrexate treatment in corticosteroid-dependent asthma. AB - STUDY OBJECTIVE: To study the long-term efficacy and toxicity of low-dose methotrexate as corticosteroid-sparing adjunctive therapy in patients with corticosteroid-dependent bronchial asthma. DESIGN: A prospectively evaluated case series. PATIENTS: We studied 31 cushingoid asthmatics who needed daily prednisone and were found to be unable to reduce their prednisone dosage. These patients had used maximal daily doses of bronchodilator and inhaled corticosteroid and, on average, had used prednisone, 26.8 mg/d, for 4.7 years (range, 1 to 11 years). Of these 31 patients, 25 completed 18 to 28 months of methotrexate therapy. INTERVENTION: Patients were treated for at least 18 months with low-dose methotrexate (range, 15 to 50 mg/wk). RESULTS: The mean prednisone dose was reduced from 26.9 mg/d to 6.3 mg/d (P = 0.0001) in the 25 patients treated with long-term methotrexate: Fifteen patients discontinued the regular use of prednisone, 9 patients reduced prednisone use by more than 50%, and 1 patient failed to respond. The forced expiratory volume in 1 second (FEV1) improved from 1.7 L/s to 1.9 L/s (P = 0.0513), and subjective symptom scores for breathing ability, cough, wheeze, and frequency of nocturnal awakenings all improved. Adverse drug reactions were noted in 15 patients. These reactions were mild and did not lead to discontinuation of drug therapy. CONCLUSION: Methotrexate is effective and safe when used as a long-term, corticosteroid sparing agent in patients with severe bronchial asthma. PMID- 2327678 TI - Tracheobronchial foreign bodies in adults. AB - STUDY OBJECTIVE: To define the clinical spectrum of tracheobronchial foreign body aspiration in adults, assess predisposing conditions, evaluate the efficacy of bronchoscopy, and determine outcome and complications. DESIGN: Retrospective analysis of a consecutive clinical series. SETTING: A tertiary care, referral based medical center. PATIENTS: Sixty consecutive adult patients (over 16 years of age) evaluated for tracheobronchial foreign body aspiration. INTERVENTIONS: All 60 patients had bronchoscopic evaluation; 59 of them had foreign bodies identified and removal was attempted using either rigid or flexible fiberoptic bronchoscopy. MAIN RESULTS: Of 60 consecutive patients, 25 had underlying impairment of protective airway mechanisms (primary neurologic disorders, trauma with loss of consciousness, or sedative or alcohol use). Fifty-seven were successfully managed with bronchoscopy. Fiberoptic bronchoscopy was successful in 14 of 23 patients, and rigid bronchoscopy was successful in 43 of 44 patients, including 6 of 7 patients in whom previous fiberoptic bronchoscopy had failed. Thoracotomy was required in 3 patients. Complications of bronchoscopy were rare and not serious. Chronic complications of prolonged foreign body impaction included bronchiectasis in 3 patients. CONCLUSIONS: Although rare, tracheobronchial foreign body aspiration in adults can occur in various clinical settings. High clinical suspicion is necessary for diagnosis. Removal of foreign bodies can usually be accomplished with bronchoscopy. PMID- 2327679 TI - Physicians and the pharmaceutical industry. American College of Physicians. PMID- 2327680 TI - Carbamazepine-induced aseptic meningitis. PMID- 2327681 TI - The source of recurrent bacteremia identified by trans-esophageal echocardiography. PMID- 2327682 TI - Pernicious anemia and colorectal cancer. PMID- 2327683 TI - Famotidine and hyperpyrexia. PMID- 2327684 TI - Dilated pupils and brain death. PMID- 2327685 TI - Fish oil supplementation and plasma cholesterol: the power of a clinical trial. PMID- 2327686 TI - Activated carbon filters in air cleaning processes--II. Prediction of breakthrough times and capacities from laboratory studies of model filters. AB - A method based on studies of model filters is suggested for prediction of breakthrough times and capacities of activated carbon filters in local exhaust ventilation units. Toluene was used as the test substance. The method involves the determination of three penetration curve parameters from testing of the model filters. The penetration curve parameters are subsequently used in combination with a suitable predictive equation for calculating breakthrough times of large scale filters containing different amounts of activated carbon. The results indicate that the filter under investigation will have a relatively short breakthrough time under normal working conditions and it is recommended that the amount of activated carbon should be substantially increased. PMID- 2327687 TI - Occupational and socioeconomic factors associated with peptic ulcer and with cancers following consequent gastric surgery. AB - Over 3000 patients, treated surgically for peptic ulcers, were assigned to a Social Class and Occupation Group using information obtained either from their death certificates or from their hospital notes. An analysis of the relationship of socioeconomic status and occupation with the site of original ulcer and the risk of cancer is reported. The major observations were: (a) an association of gastric ulcer with manual and of duodenal ulcer with non-manual Social Class; (b) an association of gastric cancer with dusty occupation and colorectal cancer with professional and managerial workers; and (c) no association between post-surgery gastric cancer risk and social class. This implies that the early stages of gastric carcinogenesis are related to poor socioeconomic conditions but the progression from the precursor lesion (in this case gastric ulcer) to gastric cancer is not, and is consistent with the multistage hypothesis of gastric carcinogenesis proposed by Correa [Diet and Human Carcinogenesis (Edited by Joosens, J. V., Hill, M. J. and Geboers, J.), pp. 109-115. Excerpta Medica, Amsterdam (1985)]. PMID- 2327688 TI - Studies of aerosol distributions in a small laboratory containing a heated phantom. AB - In order to provide information to assist in the design and planning of workplace air-sampling facilities, we have studied the variations in time and space of aerosol concentrations in a small room containing a glove-box and a heated phantom. Aerosol concentrations are reduced by factors of 10(2)-10(3) between the source and the phantom and walls of the room. Time-series plots of concentration show large departures from mean concentrations and fluctuations measured at the mouth and chest of the phantom are frequently uncorrelated. Both the average concentration around the phantom and the fluctuations in concentration tend to increase when the phantom is heated. PMID- 2327689 TI - Exposure of welders to fumes and gases in Dutch industries: summary of results. AB - A study was made of the exposure of welders and cutters in Dutch industries to air pollution consisting of total particulate, chromium, nickel, copper, nitrogen oxides, ozone, carbon monoxide and other pollutants. Guidelines are given to help industrial hygienists to estimate the exposure of welders and cutters to chemical agents. The required reduction factors for exposure are given for various types of welding. PMID- 2327690 TI - Characterization of airborne dust in a soft paper mill. AB - The characteristics of airborne dust in a soft paper production plant have been characterized by scanning and transmission electron microscopy. A combination of X-ray diffraction, electron diffraction and energy-dispersive X-ray flouresence spectroscopy (EDX) was used to determine the structure and composition of the different components. Size distribution determination and phase identification were carried out. Besides the cellulose fibres, fibres of kaolinite, wollastonite, talc and other silicates were also identified. Gravimetric analysis and fibre counting by optical phase contrast microscopy were used to determine total dust and fibre concentrations. Total dust exposure at the plant was generally below 3 mg m-3. The respirable fraction of the total dust concentrations varied from 15 to 70%. The inorganic dust was 36 +/- 15% of the total dust. The ratio of inorganic fibres to total fibre concentration at the plant varied between 10 and 15%. PMID- 2327691 TI - The health and safety executive interlaboratory quality control scheme for isocyanates. AB - The inclusion of isocyanate analysis within the AQUA (Analytical Quality Assurance) interlaboratory quality assurance scheme was established in 1984. (The AQUA interlaboratory quality assurance scheme is equivalent to external quality assessment, in North America the term proficiency testing is preferred.) The participants include university, industrial, occupational consultant and government laboratories, both in the U.K. and abroad. The AQUA isocyanate scheme is linked to a specific analytical method. MDHS 25 [Health and Safety Executive, Organic isocyanates in air: laboratory method using 1-(2-methoxyphenyl) piperazine solution and high performance liquid chromatography. H.M. Stationery Office, London (1987)]. Results from the first 4 years of the scheme's operation are reviewed and individual laboratory performance indices assessed against the mean interlaboratory performance indices. Most of the laboratories in the scheme show a marked improvement with time, which in some instances has followed help and advice from the HSE. There has also been an overall reduction in intralaboratory variability over this period. PMID- 2327692 TI - Fibres in Lower Silesia hard coal mines respirable dusts. AB - The paper describes the presence of fibres in respirable coal dust in high rank coal mines in Lower Silesia. The amount of fibres in dust particles is about 1.5% (by count). Testing by the incineration test, the lack of atomic number contrast in electron back-scattering imaging in SEM and X-ray microanalysis allow the fibres to be identified as coal. The authors suggest the possible role of coal fibres in the increased fibrogenic activity of the dusts in coal mines in Lower Silesia. PMID- 2327693 TI - Effects of lateral manual compression upon glottic incompetence: objective evaluations. AB - Forceful manual compression of the thyroid and cricoid cartilages modifies the position, shape, and tension of the vocal folds. This is the basis of the four laryngeal manual compression tests, adjunctive examinations used as a means of preoperative assessment of patients for medialization laryngoplasty, ie, Isshiki thyroplasty types I and IV and arytenoid adduction. The laryngeal manual compression tests are simple to perform and noninvasive. Each of the four examinations yields valuable information on the effects on the voice of changes in vocal cord characteristics produced by manual compression. In this report, one of the four tests, lateral manual compression, is evaluated objectively with well attested methods of videostroboscopic, aerodynamic, and acoustic analysis. The technique of performing lateral manual compression is described, and advantages and disadvantages are noted and compared in 10 patients. Preliminary findings in 4 patients in this group indicate that medialization laryngoplasty should be considered when test results are conclusive of effective glottic closure. Data derived in this preliminary study will be augmented as patients are added to the series. PMID- 2327694 TI - Staging for cholesteatoma in the child, adolescent, and adult. AB - A closed tympanomastoidectomy with subsequent staged surgical procedures leading to the excision of cholesteatoma was validated as described. All elements of staging with a 10-year experience of 354 patients are covered according to categories of child (0 to 9 years), adolescent (10 to 15 years), and adult. The child differed from the adolescent and adult in the following manner: more recurring cholesteatomas, greater ossicular necrosis, poorer hearing results, less aggressive residual cholesteatoma, and significantly poorer results with pars flaccida cholesteatoma than pars tensa cholesteatoma. After the end stage, 90% of the cases remained closed, with acceptable hearing in 60% of the patients. PMID- 2327695 TI - Clinical diagnosis of anterior inferior cerebellar artery thrombosis. Autopsy and temporal bone histopathologic study. AB - A patient having the diagnosis of an anterior inferior cerebellar artery insufficiency died 36 hours after the onset of the symptoms that allowed this diagnosis. The special features of this study include a known symmetric 40-dB hearing loss 1 year prior to the onset of the symptoms, the noted decrease in hearing and severe vertigo heralding the vascular accident, the ensuring neurologic deficits, and the short duration of the patient's life after the onset of her symptoms. The patient's clinical course and the histopathologic findings of the brain stem involved the vestibular nuclei, facial nerve, nuclei of nerve V, restiform body and middle cerebellar peduncle and labyrinth including loss of sensory epithelium of the cochlea and vestibular system and the ganglion cells of Scarpa's ganglion. These findings are correlated with previous animal studies and those of Reye's syndrome. To the authors' knowledge this is the first report of a temporal bone histopathologic study from a patient having had the diagnosis of a labyrinthine arterial vascular accident. PMID- 2327696 TI - Prevention of aspiration in infants and young children: federal regulations. AB - Aspiration of and asphyxiation from small objects is a well-known danger to young infants and children. At present, there are three different federal regulations that address this problem, by specifying different dimensions of height, width, and length. The Small Parts Regulation, which affects toy size, is the least stringent and is being challenged. The anatomic and physiologic concepts behind these important regulations are analyzed and discussed. The idea of a single generic standard is also reviewed. PMID- 2327697 TI - Human leukocyte antigens -A, -B, -C, and -DR and nasopharyngeal carcinoma in northern China. AB - We observed HLA associations in patients with nasopharyngeal carcinoma from northern China. There was an increased risk of nasopharyngeal carcinoma associated with HLA-B35 and a difference in the HLA association between patients with early- and late-onset disease. The frequency of B35 was significantly higher in patients than in control subjects, especially in early-onset patients (less than 30 years old). Late-onset patients had a higher frequency of DR2 as compared with normal subjects. PMID- 2327698 TI - Variability of the surgical anatomy of the neurovascular complex of the cerebellopontine angle. AB - The variability of the anatomic relationship of the anterior inferior cerebellar artery (AICA) to the facial (seventh) and vestibulocochlear (eighth) nerves was studied in 52 cerebellopontine angles (CPAs) from 26 adult cadavers. The AICA originated from the basilar artery (98.1%) or from the vertebral artery (1.9%) as a single (92.3% of CPAs) or duplicate (7.7%) artery. Each of the 52 CPAs had one or more arterial trunks that coursed in close proximity to the seventh and eighth cranial nerves and thus were said to be nerve-related. The nerve-related arterial trunks were divided into three segments based on their relationship to the nerves and meatus: the premeatal, meatal, and postmeatal segments. The nerve-related branches of the AICA gave rise to the internal auditory artery in 92.3% of the CPAs, the recurrent perforating artery in 78.8%, and the subarcuate artery in 30.8%. The importance of understanding the surgical anatomy of the neurovascular complex of the CPA when performing a vestibular neurectomy is reviewed. PMID- 2327699 TI - Malignant hyperthermia in the otolaryngologic patient: prospective anesthetic and surgical management of eight children. AB - Malignant hyperthermia (MH) is a rare genetic myopathy whose hallmark is rise in body temperature. This hypermetabolic state is triggered by inhalational anesthetics and/or depolarizing muscle relaxants such as succinylcholine. Even the use of dantrolene may not be protective against the hypermetabolic crisis. Eight patients at risk for MH undergoing tonsillectomy, adenoidectomy, and/or myringotomy with ventilation tube insertion were anesthetized with nitrous oxide, barbiturates, opiates, tranquilizers, and nondepolarizing muscle relaxants without dantrolene and without complication. Cardiac monitoring and rectal temperatures were followed. In order to provide additional evidence, all eight patients had vastus lateralis muscle biopsies with subsequent caffeine-halothane contracture studies performed. The contracture study showed positive results in seven of eight patients studied, indicating MH-susceptible muscle. No anesthetic or operative complications were encountered. This study demonstrates that patients at risk of developing MH crisis can have otolaryngologic procedures performed relatively safely while undergoing appropriately selected anesthesia. PMID- 2327700 TI - Cancer of the tongue base treated by a transpharyngeal approach. AB - Tongue base resection plays an important role in the management of the patient with cancer of the posterior tongue. The considerable morbidity resulting from loss of functional tongue includes compromised deglutition, chronic aspiration, and altered speech articulation. The particular operative approach used dictates additional secondary morbidity, which may include cosmetic and functional defects of the mandibular arch, malocclusion, lip and chin scars, and postoperative changes in the oral cavity. Our recent experience with a transpharyngeal approach in 13 patients with tongue base cancer is reviewed. Adequate operative exposure was obtained in all cases. Persistent aspiration was not a problem, and all patients learned to swallow effectively. The transpharyngeal approach avoids unnecessary surgical trauma to the mandible and anterior oral cavity and minimizes cosmetic deformity. Our early experience with this approach is encouraging. PMID- 2327701 TI - Anomaly of the hypoglossal nerve: embryologic, anatomic, and surgical considerations. AB - An anomaly of the hypoglossal nerve was discovered during a procedure to anastomose the 12th and 7th cranial nerves. This anomaly is described, and an embryologic mechanism is proposed to explain the occurrence of this particular anomaly. The surgical anatomy of the hypoglossal nerve is reviewed, and reasonable approaches to the surgical identification of the hypoglossal nerve are discussed. PMID- 2327702 TI - Lermoyez's syndrome: histopathologic report of a case. AB - This paper reports findings in a pair of temporal bones from a patient with clinical evidence of Lermoyez's syndrome, a rare variant of Meniere's disease. Endolymphatic hydrops is limited to the basal turn of the cochlea and saccule in Lermoyez's syndrome, but more generalized in Meniere's disease. PMID- 2327705 TI - The mechanical mind. PMID- 2327703 TI - Histopathologic study of the perilymph-suctioned labyrinth. AB - A small amount of perilymph was suctioned from the scala tympani through the round window membrane of guinea pigs. The animals either were killed immediately after the suctioning or were kept alive for 1 to 3 months. For morphologic study, the conventional celloidin embedding method was employed, and the temporal bones were serially sectioned. Various kinds and degrees of changes in the membranous labyrinth were observed: hydrops, collapse, and rupture. Loss of outer hair cells in the upper turns of the cochlea was noted in the 1- to 3-month recovery specimens. These findings are identical to those found in animals in which artificial perilymph was injected into the subarachnoid space in order to produce experimental perilymphatic fistula. After comparing morphologic changes of the membranous labyrinth following use of each method, we concluded that perilymph suctioning from the round window can be used as an animal model of perilymphatic fistula. PMID- 2327704 TI - Maxillary sinus mucocele. PMID- 2327706 TI - Changes in size and zinc protoporphyrin/haemoglobin ratio in red cells of infants during the first months of life. AB - A longitudinal investigation of changes in red blood cell (RBC) size distribution and zinc protoporphyrin/haemoglobin (ZPP/Hb) ratio was performed. In the course of the first few weeks after birth RBC size distribution histograms show a loss of macrocytic RBCs demonstrated by a rapid decrease of the fraction of macrocytes, whereas the degree of RBC volume dispersion decreases simultaneously. Within this period a significant change in the fraction of microcytes was not observed. At about 6 months of age, a marked shift of RBC size distribution histograms towards lower volumes occurs. Concomitant with the lower MCV values, the values for the absolute distribution width at half peak height (ADW0.5) also showed an obvious decrease. At birth, ZPP/Hb ratios are about three times higher than those of adult subjects and decrease slowly during infancy. This suggests that iron deficiency is unlikely in the first months of life. PMID- 2327707 TI - The relationship between serum cholesterol and serum thyrotropin, thyroxine and tri-iodothyronine concentrations in suspected hypothyroidism. AB - The relationship between serum cholesterol, thyrotropin, thyroxine and tri iodothyronine was investigated in 1018 female patients over 40 years of age with suspected hypothyroidism. The correlation between serum thyrotropin and cholesterol (r = 0.398) and between thyroxine and cholesterol (r = -0.217) were both highly significant (P less than 0.001), but the correlation between tri iodothyronine and cholesterol (r = -0.011) was not significant. Only in patients with a serum thyrotropin in excess of 40 mU/L was there a clinically appreciable increase in the serum cholesterol. In 139 patients treated for hypothyroidism by thyroxine replacement there was a highly significant correlation (P less than 0.001) between the decrease in serum thyrotropin and cholesterol (r = 0.593). The correlation between increase in serum thyroxine and decrease in cholesterol (r = 0.401) was also highly significant (P less than 0.001), but there was an even stronger correlation between the increase in serum tri-iodothyronine and the decrease in serum cholesterol (r = -0.529). PMID- 2327708 TI - A theoretical study of carryover in selective access analysers. AB - Carryover in selective access analysers is of two types: physical (specimen) and chemical (reagent) carryover. There are four constants describing carryover of each analysis: s, the batch carryover constant; k, the interaction constant; m, the slope constant for reagent carryover; and C, the intercept constant for reagent carryover. Procedures to measure these constants are described, and equations to allow correction of results for specimen and reagent carryovers in computer supported instruments are developed. PMID- 2327709 TI - Laboratory instrument evaluation using a personal computer. AB - A system in which data from multichannel biochemical analysers is downloaded to a personal computer using a communications package is described. BASIC programs were developed to format the data into a file structure suitable for importing into a commercial statistics software package. This allowed statistical comparisons to be made of patient data obtained from different instruments and facilitated evaluation of these instruments. Using this technique, many hundreds of patient results may be compared without requiring the data to be keyed into a computer. The techniques and programs used are described to show that these facilities can be developed by laboratory scientists with only rudimentary computer programming skills. PMID- 2327710 TI - Interference by haemoglobin with the cresolphthalein complexone method for serum calcium measurement. AB - The spectral interference caused by haemoglobin in the calcium-cresolphthalein complexone reaction was investigated. The results show that the nature of the haemoglobin derivative in the reaction mixture influences the degree of interference; in turn, the derivative formed depends on the order in which the sample and reagents are added. Methods using a single, alkaline cresolphthalein complexone reagent are most seriously affected by haemolysis due to persistence of oxyhaemoglobin. If the sample is added to an acid cresolphthalein complexone reagent then acid haematin is formed, this being converted to a different derivative on the addition of alkali, producing less pronounced interference. The addition of the sample to a buffer, followed by addition of complexone, appears to offer a means to correct for moderate haemolysis in the sample. PMID- 2327711 TI - How well do nurses perform blood glucose analyses at the diabetic clinic? An assessment using the Reflotron analyser. PMID- 2327713 TI - Cardiology. PMID- 2327712 TI - Reference ranges for serum creatinine in infants, children and adolescents. AB - Reference ranges for serum creatinine, derived from 2110 cases aged between 1 day and 20 years, are presented. Levels fall during the neonatal period and then increase with age in both sexes. Levels fall more rapidly in full term infants than in premature infants and are significantly higher in males than in females aged 15 years and above. PMID- 2327714 TI - The coming of age of cardiology in Singapore. PMID- 2327715 TI - Current status of arrhythmia surgery. PMID- 2327716 TI - Ventricular septal rupture in acute myocardial infarction. AB - This is a review of 31 patients with ventricular septal rupture occurring in myocardial infarction which have been managed at the Singapore General Hospital. Ventricular septal rupture occurs more frequently in the elderly, in females and those presenting with the first myocardial infarction. Very few have a prior history of stable angina pectoris before the myocardial infarction. Sudden deterioration as manifested by an increase in heart rate, fall in blood pressure and signs of right heart failure in a patient with acute myocardial infarction (AMI) especially if accompanied by a systolic murmur should encourage a search for a mechanical cause, especially a ventricular septal rupture. 2D echocardiography or Swan-Ganz catheterisation are 100% diagnostic and can be easily and rapidly done at the bedside. Medical management includes vasodilator therapy and inotropic support. Intra-aortic balloon counterpulsation is especially useful and was instituted in 6 patients. Early surgical repair of the ventricular septal defect is important if overall prognosis of these patients is to be improved. Our operative survival of 42.9% is comparable to others, considering that without surgery all have died. Survival appears to be related to the site of the myocardial infarction (very poor prognosis in inferior myocardial infarction), operative treatment (no survivors if treated conservatively) and the mode of presentation (poor prognosis in patients who develop a ventricular septal rupture while in hospital). PMID- 2327717 TI - Pattern of acute myocardial infarction in a district hospital in Brunei Darussalam--a pilot study. AB - The objective of the authors was to study the pattern of presentation, risk factors, and natural course of acute myocardial infarction in the general population of Belait District in Brunei Darussalam. A prospective study was done of 100 consecutive cases of acute myocardial infarction admitted to the coronary care beds of a District General Hospital. The patients were followed up to 12 weeks after admission to hospital. There were three times more males than females (75 males, 25 females). Nine cases out of 75 males were below the age of 40 years, 3 being below 30 years. The mean age of the male denominator was 57.4 years while that of the female counterpart was 67.48 years showing a mean difference of 10.08 years. There were significant association with hypertension (31%), smoking (30%) and diabetes mellitus (27%). The majority of the patients had prodromal symptoms, the most common presenting symptoms were chest pain (63%) and shortness of breath (27%). Only 4% of the patients had silent infarction. Acute myocardial infarction is common in Brunei forming 2.6% of all the patients admitted to the medical wards and the relative rate is 3 times higher in males than in females. There is significant association of IHD with 3 main risk factors namely hypertension, smoking and diabetes mellitus. PMID- 2327718 TI - The use of intravenous streptokinase (SK) in a peripheral hospital in the treatment of acute myocardial infarction. AB - We report our early experience in the use of intravenous Streptokinase in acute coronary occlusion in a peripheral hospital. From 1st November 1988 to 20th July 1989, 30 patients were treated with Streptokinase. The hospital mortality was 1/30 (3.3%) from a non-streptokinase related event. The commonest complication following streptokinase infusion was transient hypotension, affecting 10/30 patients. From a total of 30 patients, 3 had transient bleeding complications and was self limiting. Follow up coronary angiograms were performed on 17/30 patients, demonstrating a patent infarct related artery in 12/17 patients (70.6%). We concluded that it is both feasible and safe to use intravenous streptokinase in a peripheral setting in the treatment of acute myocardial infarction. PMID- 2327719 TI - Mortality trends in the coronary care unit. AB - To evaluate the clinical features, complication rates, and mortality from infarction in the coronary care unit, we analysed all cases of acute myocardial infarction admitted to the Coronary Care Unit of the Singapore General Hospital over a 4 month period in 1988. There were 184 cases of acute infarction with a male:female ratio of 3.4:1. Fifty-five percent of patients were aged 60 years or above. Complications included congestive cardiac failure in 40%, sustained ventricular tachycardia in 9%, cardiogenic shock in 18% and complete heart block in 8%. The overall in-hospital mortality was 20.6%. Multiple logistic regression analysis of clinical variables showed that of the clinical variables, age (elderly patients) and the diabetes were independently associated with a higher mortality as well as development of cardiogenic shock and sustained ventricular tachycardia. Comparing our results with previous smaller studies of CCU outcome in 1975 and 1967, there was a marked increase in the proportion of elderly patients in 1988 but despite this the overall mortality rate was not significantly different. Age is the most important clinical variable predicting outcome from infarction. PMID- 2327720 TI - Coronary risk profile screening during National Heart Week--1986. AB - Coronary risk profile screening was performed in 1422 volunteer subjects during National Heart Week 1986. A great proportion (55%) of this study group had blood cholesterol above 200 mg/dl; 10% of the subjects were smokers. This study documents the coronary risk profile of 1422 subjects whose biodata provide a baseline for future follow up of the possible changes in any of the various risk factors. This study identifies modifiable risk factors, high blood cholesterol and smoking which should be the target of public education in the efforts to reduce coronary diseases in Singapore. PMID- 2327721 TI - Coronary artery bypass in patients with impaired left ventricular function. AB - Myocardial revascularisation in patients with severe left ventricular dysfunction has been shown to improve survival. This report analyses the efficacy of myocardial revascularisation in this subset of patients with coronary artery disease manifesting severe left ventricular dysfunction on the basis of left ventricular ejection fraction (LVEF). Twenty-two consecutive patients with coronary artery disease complicated by severe left ventricular dysfunction underwent aorta-coronary bypass electively at Singapore General Hospital for the 3 year period ending February 1989. Twenty-one patients have angina +/- congestive heart failure refractory to medical therapy. One patient had congestive heart failure and objective evidence of ischaemia confirmed by preoperative thallium stress test. Nineteen (82.6%) patients had triple-vessel coronary artery disease. The mean LVEF for the series was 25% with the range from 10-13%. The duration of follow up was 6 months to 3 years (mean 24 months) with follow up survival data on 100% of patients. The hospital mortality was 9% (2/22) and there were 3 late deaths. Of the 17 survivors available for direct assessment, 12 reported improvement in their symptoms and 3 are completely asymptomatic. These preliminary results indicate that myocardial revascularisation can be performed in patients with severe LV dysfunction at an acceptable risk and that operation results in improvement in survival expectation and symptoms compared with medical therapy. PMID- 2327722 TI - Left main coronary artery obstruction: surgical experience with 93 patients. AB - Among patients with ischemic heart disease, those with left main stem coronary artery stenosis has attracted most attention due to their ominous prognosis. During the period from August 1982 to February 1989, 93 patients underwent left main coronary artery revascularisation procedures at Singapore General Hospital. All the patients had greater than 75% obstruction of the left main coronary artery. Significant triple vessel disease occurred in 35 patients (37.6%), double vessel disease in 32 patients (34.4%), single vessel disease in 21 patients (22.6%) and left main coronary as an isolated lesion in 5 patients (5.4%). The overall hospital mortality rate is 6.5% and perioperative infarction rate is 8.6%. Since mid-1985, the hospital mortality rate has been reduced to 3.7% and the perioperative infarction rate to 4.9%. Average grafts per patient was 3.5. Intra-aortic balloon pump was used in 5 patients. Follow up period was from 5 months to 84 months with a mean of 36 months with the majority of patients in either New York Heart Association Class I or II and still alive. PMID- 2327723 TI - The role of protamine dose assay in reversal of heparin following extracorporeal circulation for open heart surgery. AB - The amount of protamine required for the neutralisation of heparin following cardiopulmonary bypass was determined by a Protamine Titration Assay using the principle of the dose--response curve and the patient's estimated blood volume. In 300 open heart surgery patients, infusion of the determined dose of protamine normalised the Activated Clotting Time (ACT) to baseline levels in 97% of these patients and produced adequate hemostasis. Our present study showed that the dose of protamine dropped to 75% of the dose calculated by conventional method of heparin to protamine ratio of 1:1. This had minimised the adverse effects of excessive protamine administration and optimised coagulation control after extracorporeal circulation. PMID- 2327724 TI - Coronary artery bypass surgery in the elderly. AB - This review of all patients operated on for isolated coronary artery disease from January 1985 to June 1989, was undertaken to determine the impact of advancing age on their final outcome following coronary artery bypass grafting. Three hundred and seventy patients were studied, 147 (39.7%) were less than 55 years old, 141 (38.1%) between 55 and 64 years, 55 (14.6%) between 65 and 69 years and 28 (7.6%) were aged 70 years and above. There were 10 deaths (2.7%) and 99 complications (26.8%). Using univariate analysis, advance age, the presence of some concomitant diseases, poor left ventricular function and left main stem disease were found to be significant risk factors. Patients with four or more grafts and those who underwent emergency or urgent surgery were also at greater risk of developing complications including death. Multivariate regression analysis revealed that increasing age beyond 65 years was an independent risk factor. Inspite of the above findings, it is recommended that elderly patients with uncontrollable unstable angina should not be denied surgery in view of their improved quality of life after surgery. PMID- 2327725 TI - Balloon atrial septostomy under two dimensional echocardiographic visualisation. AB - From May 1988 to January 1989, we performed balloon atrial septostomy under Two Dimensional Echocardiographic visualisation on 8 patients at the bedside in the intensive care unit, in the Singapore General Hospital. Their ages ranged from 3 to 45 days (median = 7 days). Their weights ranged from 1.6 to 4.0 kg (mean +/- 2sd = 3.2 + 1.6). Five patients had transposition of the great arteries, 1 had tricuspid atresia and 2 with pulmonary atresia/stenosis. There were no complications related to the procedure. The advantage of Two Dimensional Echocardiographic imaging compared to fluoroscopy are 1) excellent visualisation of cardiac structures, 2) it can be performed safely at the bedside without transporting patient to the cardiac catheter laboratory, 3) Immediate detection of cardiac complications and 4) no radiation exposure. Balloon atrial septostomy done using Two Dimensional Echocardiographic visualisation is acceptable and safe. It is the method of choice in our department. PMID- 2327726 TI - Percutaneous transluminal balloon valvuloplasty: the treatment of choice for congenital valvar pulmonary stenosis. AB - Forty-eight children with suspected isolated pulmonary valvar stenosis were evaluated clinically and echocardiographically between January 1987 and December 1988. Fourteen patients with significant transpulmonary peak systolic pressure gradient greater than 30 mmHg on continuous-wave Doppler interrogation were subjected to right heart catheterisation. Percutaneous transluminal balloon valvuloplasty was performed in 11 of these patients with peak systolic pressure gradient than 40 mmHg across the pulmonary valve at cardiac catheterisation. Satisfactory reduction of systolic right ventricular pressure (110 +/- 43 to 46 +/- 17 mmHg, p less than 0.001) and peak systolic pressure gradient across pulmonary valve (92 +/- 44 to 27 +/- 16 mmHg, p less than 0.001), were achieved in all cases. The reduction of peak systolic pressure gradient (64 +/- 37 mmHg, range = 29-158 mmHg), was positively correlated with the initial right ventricular systolic pressure (r = 0.92, p less than 0.0002). There was no significant complication in this series and all patients were discharged the day after the procedure. Percutaneous transluminal balloon valvuloplasty is effective and safe. It should be the treatment of choice for significant valvar pulmonary stenosis in children. PMID- 2327727 TI - Anti-arrhythmic surgery for atrioventricular junctional and atrioventricular re entrant tachycardia--a report of six cases. AB - Since 15th March 1989, six patients with recurrent supraventricular tachycardia (SVT) had antiarrhythmic surgery performed. There were 4 males and 2 females, ages ranged from 23 to 62 years (mean 41 years). Two of these patients with the Wolff Parkinson White (WPW) syndrome also had syncope. Five of these patients had atrioventricular re-entrant tachycardia (AVRT) involving the bypass tracts. Two patients with the WPW syndrome had persistent antegrade conduction, two had intermittent conduction and the last patient had no antegrade conduction via the bypass tract. The bypass tracts were localised at the left free wall in all the five patients. Only one patient had atrioventricular junctional re-entrant tachycardia (AVJRT) of the slow-fast type. The indications for surgery for these patients include failed medical therapy, "dangerous" arrhythmias and patient's preference. All the patients had surgery performed using the endocardial dissection technique on the cardioplegic heart. There were no perioperative mortality and morbidity. All the patients were discharged within 2 weeks. To date, none of the patients had clinical recurrence of SVT and only one patient remained in atrial fibrillation and is on digoxin. In conclusion, antiarrhythmic surgery should be considered for patients with "symptomatic" palpitations as it is curative with a resumption to normal life. PMID- 2327728 TI - Permanent pacemaker trends in Singapore General Hospital in the eighties. AB - This is a ten year survey of all the pacemakers implanted in the Department of Cardiology, Singapore General Hospital, from January 1980 to July 1989. There were 331 (164 male and 167 female) patients with pulse generators and leads implanted. The ages of the subjects ranged from 8 to 91 years (mean 63 years). Two-thirds of the patients were greater than 60 years. The indications for pacemaker implants were high grade atrioventricular block in 199 (60%) patients, sick sinus syndrome in 112 (34%) patients and in the remaining 20 (6%) of patients, no data was available, 298 (90%) patients had VVI pacing (133 were non programmable and 165 were programmable pacemakers), 8 (2%) had AAI, 16 (5%) had DDD and the remaining 9 (3%) had VVIR mode of pacing. 282 (85%) of the patients had new pacemakers implanted while the remaining 49 (15%) patients had pacemaker replacements. At the time of replacement of pacemakers, 23 patients had upgrade of their non-programmable to programmable VVI pacemakers and 4 to DDD and VVIR pacing modes respectively. Furthermore, 293 (88%) patients had endocardial leads as compared to 38 (12%) with epicardial leads. In conclusion, most of the patients who require pacemaker implants will continue to have single chamber system. However, to improve longevity of the pacemakers, one should consider using low pacing threshold leads and programmable pacemakers. PMID- 2327729 TI - Low levels of unsaturated transferrin as a predictor of survival in pneumococcal pneumonia. AB - A study was conducted to evaluate factors which might influence the prognosis of persons with pneumonia owing to Streptococcus pneumoniae. Serum iron, total iron binding capacity and unbound iron binding capacity (UIBC), were evaluated in 35 such patients. Of the 10 patients with UIBC levels less than 130 micrograms per dl on admission to the hospital, six died, three had complications, and only one recovered uneventfully. Of the 25 surviving patients, 21 (84 percent) had UIBC greater than 130 micrograms per dl on admission. Positive blood cultures were also correlated with survival. However, the strongest prognostic indicator was the combination of UIBC and blood culture results. Only 14 percent of patients with abnormalities in both parameters survived, whereas 80 percent to 88 percent of those with negative blood culture and/or normal UIBC survived. This suggests that insufficient unsaturated transferrin may facilitate bacteremia and contribute to lethality of pneumococcal pneumonia. PMID- 2327730 TI - Renal vascular lesions in systemic lupus erythematosus. AB - In the past, necrotizing vasculitis has been considered to be one of the dominant intrarenal vascular abnormalities in systemic lupus erythematosus (SLE). To test the validity of this statement, 70 consecutive renal biopsies from patients with SLE were reviewed. Light microscopy (LM) and immunofluorescence (IF) studies documented abnormalities, including thrombosis and nephrosclerosis, in 30 patients (43 percent), but no cellular infiltration of the vessel walls or other evidence of acute necrotizing vasculitis was seen. It is concluded that while intrarenal vasculopathy with thrombosis and nephrosclerosis is a common finding in SLE, our data and recently published studies suggest that acute necrotizing vasculitis occurs rarely, if at all, in SLE nephritis. PMID- 2327731 TI - Our world of science. PMID- 2327732 TI - Degeneration of spinocerebellar neurons in amyotrophic lateral sclerosis. AB - The selective involvement of spinocerebellar neurons in sporadic amyotrophic lateral sclerosis was investigated using two monoclonal antibodies that have neuronal subset specificity in human spinal cord. In normal control subjects, monoclonal antibody 6A2 showed specificity for neurons of the dorsal nucleus of Clarke, the cells of origin of the dorsal spinocerebellar tract. Immunoreactive neurons were also observed in locations corresponding to the central cervical nucleus and spinal border region, containing neurons of the cervicospinocerebellar and ventral spinocerebellar tracts, respectively. The latter two neuronal subsets are indistinguishable from surrounding neurons when conventional histological stains are used. Antigen 6A2 was distributed on surfaces of neuronal somas and proximal neurites and extended into the extracellular space. A second antibody, monoclonal antibody 44.1, labeled the cytoplasm of neuronal somas and neurites, including all monoclonal antibody 6A2 reactive cells and alpha motoneurons. In spinal cords of all 5 patients with amyotrophic lateral sclerosis, monoclonal antibody 6A2 reactivity in the majority of spinocerebellar neurons was absent or localized to the somal cytoplasm, which still stained with monoclonal antibody 44.1. In more severely involved tissues, there was loss of some spinocerebellar neurons and a corresponding loss of monoclonal antibody 44.1 reactivity. These findings confirm involvement of the spinal cord components of the spinocerebellar system at all levels in sporadic amyotrophic lateral sclerosis and suggest that some surface molecules are modified during the degenerative process. PMID- 2327733 TI - Delineation of single-word semantic comprehension deficits in aphasia, with anatomical correlation. AB - In 3 of 18 aphasic patients pure deficits in semantic comprehension at the single word level were defined through a series of tasks that excluded possible confounding deficits in auditory perception, visual perception, or speech production. In these pure cases, deficits were found at the superordinate, equivalence, and subordinate levels of single-word semantic processing. Pure semantic deficits were found to be correlated with damage to the left posterior temporal and inferior parietal region; patients whose damage spared this area did not evince such deficits, and the converse was also true. This study confirms the existence of separable deficits in semantic comprehension and points conclusively to the left posterior temporal and inferior parietal region as being critical for semantic processing. This anatomical localization is in keeping with anatomical studies from nonhuman primates, suggesting that these regions may be concerned with multimodal processing and integration of language. PMID- 2327734 TI - A survey of epileptic disorders in southwest France: seizures in elderly patients. AB - An underestimation of epileptic seizures occurring in aged patients is likely. In an epidemiological survey undertaken in Southwest France, the annual incidence rate per 100,000 persons 60 years or older was 127.2 for all seizures (101.3 in persons aged 60 to 69, 150.4 in those aged 70 to 79, and 139.9 in persons 80 years or older). It was 34.1 for symptomatic localization-related and undetermined epilepsies, 16.1 for isolated seizures, and 77.0 for seizures related to an acute situation, such as metabolic derangements, stroke, or head trauma. In this survey, seizures with an onset age of 60 or older represented 28.0% of the confirmed epilepsies, 17.5% of the isolated seizures, and 52.6% of the acute symptomatic seizures. These figures differ dramatically from those in most previous reports concluding that age-specific incidence declined through adult life. They are closer to the data from more recent reports. The main reason for such a high incidence of epileptic seizures in elderly patients is the number of acute symptomatic (or situation-related) seizures. However, even chronic epilepsies increase in frequency in aging persons. Cerebrovascular disease was the most frequently recognized origin (53.9% of the patients with confirmed epilepsies) and brain tumor was found in 32.9% of the patients. PMID- 2327735 TI - The diagnosis and treatment of cerebral mycotic aneurysms. AB - Seventeen patients were treated for 28 documented cerebral mycotic aneurysms. Initial neurological symptoms were attributable to aneurysm rupture in only 7 patients, and in 3 of them symptoms did not suggest subarachnoid hemorrhage. Six patients presented with embolic infarction and 1 with meningitis; in 3 patients it was uncertain if aneurysm rupture occurred. Four patients had rupture of at least one aneurysm while receiving appropriate antibiotic treatment and another had rupture at the conclusion of therapy. Of 20 aneurysms followed angiographically or with computed tomography during medical treatment, 10 became smaller or disappeared and 10 remained unchanged or enlarged, 1 with fatal rupture. Eight ruptured aneurysms were surgically excised; 2 of the patients with ruptured aneurysms died and 2 had residual aphasia or cognitive impairment. All 4 patients whose only surgery was for an unruptured aneurysm made uneventful recoveries. Recognizing the retrospective and anecdotal nature of our data and the differing views of previous investigators, we recommend: (1) that careful neurological examination, computed tomography, and (unless contraindicated) lumbar puncture be performed on any patient with endocarditis; (2) that those with neurological abnormalities not attributable to systemic toxicity, including pleocytosis in the cerebrospinal fluid or apparent infarction on computed tomographic scans, undergo four-vessel cerebral angiography; (3) that single accessible mycotic aneurysms in medically stable patients be promptly excised, with individualization of multiple or proximal aneurysms; and (4) that repeat angiography be performed at the conclusion of antibiotic therapy in patients requiring long-term anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327736 TI - The distribution of chromogranin A-like immunoreactivity in the human hippocampus coincides with the pattern of resistance to epilepsy-induced neuronal damage. AB - The distribution of chromogranin A-like immunoreactivity in the hippocampus of adult humans who were free of neurological disease was examined by immunohistochemical methods. Immunoreactivity was restricted to the cytoplasm of certain neuronal populations, most notably the mossy fibers of denate granule cells (and a subset of their perikarya), and the perikarya of pyramidal cells of the cornu Ammonis 2 (CA2) sector. Additionally, staining was observed in neurons in the stratum oriens, a population of neurons at the periphery of the CA4 sector, scattered, probably short-axon perikarya in the CA1 sector, and fibers in the perforant path and the molecular layer of the dentate gyrus. Pyramidal neurons in the CA1 and CA3 sectors were not immunoreactive. The two prominently immunoreactive neuronal populations, CA2 pyramids and dentate granule cells, are those spared in human and experimental epileptic brain damage, whereas CA1 and CA3 pyramids, lacking chromogranin, are characteristically destroyed in this condition. The known activities of chromogranin in the periphery as a calcium binding protein and as a precursor of active peptides (autocrine inhibitory modulators) suggest that its distribution in the hippocampus may help to explain the observed pattern of resistance to epileptic brain damage. PMID- 2327737 TI - Localization of epileptic foci using a large-area magnetometer and functional brain anatomy. AB - We used a large-area, 7-channel, first-order superconducting quantum interference device (SQUID) gradiometer to preoperatively determine the sites of epileptic foci in 2 patients with intractable temporal lobe seizures. The equivalent dipoles for the epileptic spikes were located with respect to external landmarks of the skull and in relation to the generation sites of magnetic auditory evoked responses. It was also possible, for the first time, to determine the location of the equivalent source using simultaneously measured data from seven locations only. The sites of the equivalent dipoles, in the right temporal lobe, agreed with the electrocorticographic and depth electrode recordings made during the operation. PMID- 2327738 TI - Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjogren's syndrome. AB - Thirteen patients, 11 women and 2 men, developed sensory and autonomic neuronopathies in association with features of primary Sjogren's syndrome. In 11, Sjogren's syndrome had not been previously diagnosed at the time of neurological presentation. All had prominent loss of kinesthesia and proprioception. Pain and thermal sensibility were less severely affected. Most had evidence of autonomic insufficiency. In some this was severe, with Adie's pupils, fixed tachycardia, and orthostatic hypotension. The course ranged from an abrupt, devastating onset to indolent progression over years. Stabilization or functional improvement occurred in 6 patients, 2 of whom received no drug therapy. Sensory nerve conduction studies and examination of nerve biopsy specimens demonstrated a wide spectrum in the severity of loss of large myelinated fibers. The cutaneous nerves of 6 patients had perivascular mononuclear infiltrates without necrotizing arteritis. Examination of biopsy specimens of dorsal root ganglia in 3 patients revealed lymphocytic (T-cell) infiltration in the dorsal roots and ganglia, with focal clusters around neurons. In the more mildly affected ganglia, individual sensory neurons were undergoing degeneration. In the most advanced case, very few neurons remained. The possibility of Sjogren's syndrome should be considered in patients, especially women, who develop acute, subacute, or chronic sensory and autonomic neuropathies, with ataxia and kinesthetic loss. PMID- 2327740 TI - Traumatic brain injury: a silent epidemic. PMID- 2327739 TI - Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies. AB - We studied 74 patients with progressive, asymmetrical lower motor neuron syndromes. Clinical features of these patients, including age, sex, disease duration, patterns of weakness, and reflex changes, were evaluated by review of records. In each patient the clinical features were compared to the type of nerve conduction abnormalities and to the specificities of high-titer serum antiglycolipid antibodies. Antibody specificities were determined by an enzyme linked immunosorbent assay using purified glycolipids and carbohydrates as substrates. Our results show that high titers of antibodies to glycolipids are common in sera of patients with lower motor neuron syndromes. Selective patterns of reactivity indicate that specific carbohydrate epitopes on the glycolipids are the targets of the high-titer antibodies in individual patients with lower motor neuron syndromes. Several distinct lower motor neuron syndromes can be identified based on clinical, physiological, and antiglycolipid antibody characteristics. These syndromes include multifocal motor neuropathy with evidence of multifocal conduction block on motor, but not sensory, axons and frequent (84%) high titers of anti-GM1 ganglioside antibodies; a lower motor neuron syndrome with predominantly distal weakness early in the disease course, no conduction block, and a high incidence (64%) of anti-GM1 antibodies; and a lower motor neuron syndrome with predominant early weakness in proximal muscles and serum antibodies to asialo-GM1 that do not cross-react with GM1 ganglioside. PMID- 2327741 TI - Detection of epileptiform activity by different noninvasive EEG methods in complex partial epilepsy. AB - The diagnostic utility of different noninvasive electrode placements for deriving the electroencephalogram and detecting interictal epileptiform discharges was compared. Anterior temporal and nasopharyngeal electrodes in combination with routine scalp electrodes detected over 97% of the spikes, whereas recording from only standard electrode placements detected 58%. Minisphenoidal and surface sphenoidal electrodes were generally not helpful. In some circumstances, however, the use of surface sphenoidal electrodes provided important confirmatory information. In no case did the minisphenoidal electrodes provide unique information, and their use seems unjustified, although the inclusion of other nonstandard electrodes in the recording montage is important to increase the yield. PMID- 2327742 TI - HTLV-I-associated myelopathy, tropical spastic paraparesis, and Borrelia burgdorferi. PMID- 2327743 TI - Estimation of familial risk in Alzheimer's disease. PMID- 2327744 TI - Effect of nerve growth factor in adrenal autografts in parkinsonism. PMID- 2327745 TI - Imipenem resistance in Bacteroides distasonis mediated by a novel beta-lactamase. AB - Imipenem is a highly active drug against the Bacteroides fragilis group of organisms. On the basis of a nationwide survey of over 500 isolates, it was found that the frequency of imipenem resistance was less than 0.1%. We have a highly resistant Bacteroides distasonis isolate, TAL7860, for which the following MICs (micrograms per milliliter) were determined by agar dilution: cefoxitin, greater than 128; moxalactam, greater than 128; piperacillin, greater than 128; imipenem, 16; and SCH34343, 16. Resistance was shown to involve both a beta-lactamase and an outer membrane permeability barrier. beta-Lactamase kinetics studies with several beta-lactams, including imipenem, revealed similar hydrolytic efficiency in comparison with those found for the B. fragilis strains. An imipenem outer membrane permeability barrier was detected for TAL7860, which was approximately sixfold more effective for B. fragilis TAL3636 and TAL2480. Significant inhibition of nitrocefin destruction was also shown with sulbactam and clavulanic acid at 10 mumol and dithiothreitol at 10 mM. No inhibition was seen with 10 mM EDTA. Differences in physicochemical properties and inhibition studies suggest that this beta-lactamase is different from the imipenem-inactivating metallo-beta lactamase previously described in B. fragilis. We demonstrated a significant permeability barrier to clavulanic acid and sulbactam, which resulted in loss of synergism between these clinically employed beta-lactamase inhibitors and beta lactam drugs. The novel beta-lactamase activity in conjunction with a limited permeability in TAL7860 resulted in resistance to all commonly employed beta lactams, including the newest and most potent beta-lactam drugs. PMID- 2327746 TI - Production of cyclosporins by Tolypocladium niveum strains. AB - Nine strains of Tolypocladium niveum (= inflatum) were compared for their production of cyclosporins. Two of the strains, which were originally from the parental NRRL 8044 strain, were among the lower producers, while seventeen Tolypocladium strains belonging to seven other species produced no detectable cyclosporins. Variable cyclosporin production was observed initially. Once extraction and quantitation methods had been established, spore inoculum density and cultural morphology and carbon and nitrogen sources were found to be among the variables affecting cyclosporin production. Cyclosporin A was identified by cochromatography by using high-performance liquid chromatography, and cyclosporins A, B, and C were identified by gas chromatography-mass spectroscopy; all three compounds exhibited biological activity. They were routinely produced as a mixture in the ratio 7:1:2 in T. niveum UAMH 2472, which was selected on the basis of single-spore isolate total cyclosporin production and was used for most studies. This strain routinely produced total cyclosporin levels of 150 to 200 mg.liter-1 after 12 days of growth on a 2% sorbose-1% vitamin assay Casamino Acids medium. PMID- 2327747 TI - Effect of concomitant administration of piperacillin on the dispositions of netilmicin and tobramycin in patients with end-stage renal disease. AB - The effect of piperacillin administration on the dispositions of netilmicin and tobramycin was assessed in 12 chronic hemodialysis patients. Six subjects each received netilmicin (2 mg/kg) or tobramycin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Subjects also received a single dose of piperacillin (4 g) on a separate occasion. The serum concentration versus-time profiles of netilmicin and tobramycin were biexponential. The terminal elimination half-life (t1/2 beta) of tobramycin was markedly reduced (59.62 +/- 25.18 [mean +/- standard deviation] versus 24.71 +/- 5.41 h) and total body clearance (CLP) was significantly increased in the presence of piperacillin (3.45 +/- 1.61 versus 7.16 +/- 1.64 ml/min). In contrast, the t1/2 beta (41.80 +/ 13.24 versus 40.07 +/- 10.37 h) and CLP (5.11 +/- 2.15 versus 5.55 +/- 2.32 ml/min) of netilmicin were not significantly altered when netilmicin was administered in combination with piperacillin. No change in the central or steady state volume of distribution of netilmicin or tobramycin was observed. The disposition of piperacillin in hemodialysis patients was not altered in the presence of either aminoglycoside antibiotic. Although no adjustment in netilmicin dosing is required, tobramycin should be administered more frequently when given concomitantly with piperacillin to hemodialysis patients to avoid prolonged periods of subtherapeutic concentrations. PMID- 2327748 TI - Comparison of fluconazole and SDZ89-485 for therapy of experimental murine coccidioidomycosis. AB - We infected mice with arthroconidia of Coccidioides immitis by intraperitoneal injection and 48 h later treated them with either oral fluconazole or SDZ89-485, a new triazole. Both drugs completely inhibited fungal growth when administered at a dose of 50 mg/kg of body weight twice a day, but only SDZ89-485 was fully inhibitory at a dose of 5 mg/kg twice a day. In a second experiment, treatment with SDZ89-485 was delayed until 8 days after infection to allow infection to be well established before treatment. Both 5 and 50 mg/kg twice a day were effective regimens, which establishes that SDZ89-485 has activity against spherules in vivo. Mice that received fluconazole (50 mg/kg twice a day) had a peak level in blood of 60 micrograms/ml 1 h after a dose, but no measurable amount was found after 12 h. SDZ89-485 was more slowly absorbed, reaching a peak level in blood of 14 micrograms/ml at 12 to 15 h after a dose of 50 mg/kg. We conclude that SDZ89 485 is more effective than fluconazole as treatment for experimental systemic coccidioidomycosis in mice, even though fluconazole achieves higher peak levels in blood. PMID- 2327750 TI - Pharmacokinetics of lomefloxacin in healthy volunteers: comparison of 400 milligrams once daily and 200 milligrams twice daily given orally for 5 days. AB - We evaluated the effect of repeated oral doses (5 days of treatment) on the kinetics of lomefloxacin in volunteers and compared the kinetics after two different regimens, i.e., 400 mg once daily and 200 mg twice daily. After 400 mg of lomefloxacin was given once daily, no significant modification in the pharmacokinetic parameters was noted between the first and the fifth dose (maximum concentration of drug in serum, about 4 mg/liter; elimination half-life, about 6.3 h). After a dose of 200 mg every 12 h, a significant increase in the minimum concentration of drug in serum (0.49 +/- 0.1 and 0.72 +/- 0.2 mg/litter at days 1 and 5, respectively) and the area under the concentration-time curve (about 20%) was noted. The 400-mg regimen is probably adequate for therapeutic use. PMID- 2327749 TI - Novel sulfated polymers as highly potent and selective inhibitors of human immunodeficiency virus replication and giant cell formation. AB - Novel synthetic sulfated polymers, namely, sulfated polyvinyl alcohol (PVAS) and sulfated copolymers of acrylic acid with vinyl alcohol (PAVAS), proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in vitro. The compounds completely inhibited HIV-1-induced cytopathogenicity in MT-4 cells and HIV-1 antigen expression in CEM cells at a concentration of 0.8 micrograms/ml. They were equally effective against HIV-2 replication. In addition, and in contrast to azidothymidine, PAVAS and PVAS suppressed HIV-1-induced giant cell (syncytium) formation, a process that may account for the depletion of T4 lymphocytes in patients with acquired immunodeficiency syndrome. PAVAS and PVAS completely blocked giant cell formation at a concentration of 4 micrograms/ml, whereas for dextran sulfate a concentration of 100 micrograms/ml was required to achieve complete inhibition of giant cell formation. As has been demonstrated previously for the sulfated polysaccharides, the mechanism of action of PAVAS and PVAS resides in the inhibition of virus adsorption to the cells. PMID- 2327751 TI - In vitro susceptibility of mutans streptococci to antimicrobial substances as determined by a membrane transfer assay. AB - The in vitro susceptibilities of seven representative strains of mutans streptococci to three topically applied chemotherapeutic agents were determined by a modified membrane transfer assay. The MBCs of chlorhexidine and I2-KI ranged from 0.5 to 1.0%, while SnF2 was sublethal at the highest concentration tested (8%) in all but one strain (AHT; mode MBC, 8.0%). The proposed in vitro assay may be useful for preclinical screening of potential antimicrobial agents prior to use in the oral cavity. PMID- 2327752 TI - Diverse potential of beta-lactamase inhibitors to induce class I enzymes. AB - The ability of various beta-lactamase inhibitors to induce class I beta lactamases was assessed. Clavulanate was the most active compound, inducing Morganella morganii, Aeromonas caviae, and Enterobacter aerogenes over a broad concentration range and Citrobacter freundii, Pseudomonas aeruginosa, and Serratia marcescens at high concentrations. Disk approximation tests paralleled these results, with clavulanate, but not sulbactam or tazobactam, antagonizing the activity of several beta-lactams against these organisms. PMID- 2327753 TI - In vitro susceptibilities of Plesiomonas shigelloides to 24 antibiotics and antibiotic-beta-lactamase-inhibitor combinations. AB - The antibiotic susceptibilities of 29 isolates of Plesiomonas shigelloides were studied with 24 antibiotics and antibiotic-inhibitor combinations. Results indicated that all isolates were susceptible to the cephalosporins, penicillins combined with a beta-lactamase inhibitor, aztreonam, and ciprofloxacin. Most isolates were resistant to the penicillins, possibly via production of a penicillinase. PMID- 2327754 TI - In vivo selection for transmissible drug resistance in Salmonella typhi during antimicrobial therapy. AB - We report the recovery of Salmonella typhi that acquired resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and gentamicin subsequent to multiple antibiotic therapy. Escherichia coli and Klebsiella pneumoniae isolates which were recovered from the same stool sample displayed identical resistance patterns. Agarose gel electrophoresis revealed that S. typhi and laboratory-derived transconjugants contained a high-molecular-weight plasmid present in the resistant intestinal bacteria. PMID- 2327755 TI - Ciprofloxacin does not inhibit mitochondrial functions but other antibiotics do. AB - At clinical concentrations, ciprofloxacin did not inhibit mitochondrial DNA replication, oxidative phosphorylation, protein synthesis, or mitochondrial mass (transmembrane potential). No difference in supercoiled forms of DNA was observed. The tetracyclines and chloramphenicol inhibited protein synthesis at clinically achievable concentrations, while rifampin, fusidic acid, and clindamycin did not. PMID- 2327756 TI - Lomefloxacin pharmacokinetics in subjects with normal and impaired renal function. AB - Lomefloxacin pharmacokinetics were investigated in 6 normal subjects and 24 uremic patients after a single oral dose of 400 mg. In subjects with normal renal function, the peak level in plasma averaged 3.5 +/- 0.9 micrograms/ml (mean +/- standard deviation) and was obtained at 1.3 +/- 0.9 h. The absorption rate constant was 3.8 +/- 1.6 h-1. The terminal half-life was 7.77 +/- 0.95 h. The apparent volume of distribution was 2.54 +/- 0.66 liters/kg. Total body and renal clearances were 259 +/- 83 and 200 +/- 55 ml/min per 1.73 m2, respectively. The percentage of the dose recovered unchanged in 48-h urine was 80.6 +/- 2.8. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 38 h in severely uremic patients (glomerular filtration rate, less than 10 ml/min). Renal insufficiency did not significantly modify the peak level in plasma, the time to peak, the apparent volume of distribution, or the nonrenal clearance of lomefloxacin. The dialysis clearance of lomefloxacin was 54 +/- 13 ml/min. Linear relationships were found between lomefloxacin pharmacokinetic parameters and glomerular filtration rate data. Dosage adjustments are necessary in uremic patients. PMID- 2327757 TI - Comparison of in vitro antibiograms of Bacteroides fragilis group isolates: differences in resistance rates in two institutions because of differences in susceptibility testing methodology. AB - With 120 clinical isolates of the Bacteroides fragilis group, a comparison of rates of resistance to selected antimicrobial agents by using two susceptibility tests was performed in two medical institutions. The broth microdilution method produced MICs significantly lower than those determined by the agar dilution method. With ceftizoxime and cefoxitin, 88 and 18%, respectively, of the MICs were greater than or equal to 2 twofold dilutions apart. These differences in MIC results produced major interpretive discrepancies for ceftizoxime and cefoxitin, whereas no significant differences in resistance rates were noted for clindamycin and metronidazole. PMID- 2327758 TI - Guinea pig model for antibiotic transport across gastric mucosa: inhibitory tissue concentrations of clindamycin against Helicobacter pylori (Campylobacter pylori) following two separate dose regimens. AB - An animal model for antibiotic secretion across gastric mucosa was developed using adult guinea pigs. Antibiotics were given intramuscularly, and levels in serum and gastric mucosa were measured by high-pressure liquid chromatography at 1, 2, 4, 6, and 8 h postinjection. Mucosal levels of the drugs were measured in the superficial luminal portion of the mucosa, which was removed by mechanical scraping. Clindamycin levels were measured after doses of 10 and 100 mg/kg of body weight. After doses of 100 mg/kg, levels in serum peaked at 15.95 micrograms/ml at 2 h. Gastric mucosa showed a bimodal concentration curve with peaks of 15.91 micrograms/g at 1 h and 25.07 micrograms/g at 4 h. Concentrations in mucosa remained high when levels in serum fell, showing a mucosa/serum ratio of 87.70 after 8 h. At all times, clindamycin levels in mucosa were in excess of the MIC for 90% of the Helicobacter (Campylobacter) pylori strains tested. PMID- 2327759 TI - Pharmacokinetics of aerosol amphotericin B in rats. AB - The distributions of amphotericin B (AmB) in tissue were compared after intraperitoneal or aerosol administration. Rats were sacrificed 24 h after receiving single or repeated daily doses; AmB concentrations in tissues were determined by high-performance liquid chromatography. After intraperitoneal doses of 4 mg/kg of body weight per day for 7 days, mean concentrations of AmB were 122.7, 55.2, and 4.31 micrograms/g in the spleen, liver, and lung, respectively. After aerosol doses (aero-AmB) of 1.6 mg/kg per day, the mean concentrations of AmB in the lung were 2.79 micrograms/g after a single dose and 9.88 micrograms/g after four doses, while the drug was undetectable (less than 0.1 micrograms/g) in serum, spleen, liver, kidney, and brain. The half-life of elimination of AmB from the lungs was 4.8 days according to serial sacrifices done after a single dose of 3.2 mg of aero-AmB per kg. Treatment with 60 mg of aero-AmB per kg was well tolerated and produced no histopathologic changes in the lungs. The aerosol route was much more efficient than the systemic route in delivering AmB to the lungs, and it limited the accumulation of AmB in other organs. Because AmB is eliminated slowly, infrequent dosing schedules can be used. These pharmacokinetic characteristics and its proven effectiveness in an animal model make aero-AmB a highly promising new method for the prevention of pulmonary aspergillosis. Aero AmB should also be considered for use as an adjunct to intravenous AmB for treatment of fungal pneumonias. PMID- 2327760 TI - Purification and characterization of inducible beta-lactamases in Aeromonas spp. AB - beta-Lactamases from Aeromonas hydrophila and A. sobria were purified and characterized. Both species produced beta-lactamases that were inducible by either cefoxitin or imipenem. These species were resistant to ampicillin and cephalothin but not imipenem. Isoelectric focusing of sonic extracts revealed one band at pI 8.0 and a second band at pI 7.0 for A. hydrophila. Likewise, A. sobria produced two bands, one at pI 8.4 and the other at pI 7.0. Two enzymes from each species were separated by flatbed electrofocusing gel and purified to homogeneity. The molecular weight of the pI 7.0 enzyme (A1) from both species was estimated to be 42,500, whereas the pI 8.0 (A2h) and 8.4 (A2s) enzymes of A. hydrophila and A. sobria had molecular weights of 31,500 and 35,000, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The relative Vmax values for cephalothin, penicillin, and imipenem for these enzymes indicated that A1 was primarily a cephalosporinase while A2h and A2s were penicillinases highly active against carbapenems. A1 was susceptible to inhibition by cloxacillin, while the A2 enzymes were inhibited by clavulanic acid and EDTA and required zinc for activity. Thus, there appear to be two distinct inducible beta-lactamases in A. hydrophila and A. sobria that play an important role in the beta-lactam resistance of these species. PMID- 2327761 TI - Activities of ciprofloxacin and ofloxacin against rapidly growing mycobacteria with demonstration of acquired resistance following single-drug therapy. AB - The susceptibility to ciprofloxacin of 548 clinical isolates of rapidly growing mycobacteria belonging to eight subgroups or species was determined. The 170 isolates of Mycobacterium fortuitum biovar.fortuitum were most susceptible; the MIC for 90% of the organisms was 0.125 micrograms/ml. The other biovariants of M. fortuitum, M. smegmatis, and the M. chelonae-like organisms were less susceptible; the modal MIC was 0.5 micrograms/ml, and the MIC for 90% of organisms was 1.0 micrograms/ml. The two subspecies of M. chelonae were generally resistant, with only 8% of 206 isolates falling in the moderately susceptible category (MIC, 2 micrograms/ml) and only 2% falling in the susceptible category (MIC, less than or equal to 1 micrograms/ml). MICs of ofloxacin averaged 1 to 2 dilutions higher than those of ciprofloxacin for all subgroups tested. Three patients with M. fortuitum cutaneous disease relapsed after an initial response to therapy with ciprofloxacin, and their isolate was shown to have acquired drug resistance. Mutational frequencies for M. fortuitum with ciprofloxacin were relatively high (10(-5) to 10(-7), and MICs for single-step mutants were similar to those for the clinically resistant strains. Thus, despite the excellent activity of ciprofloxacin against rapidly growing mycobacterial groups other than M. chelonae, single-drug therapy should be used with caution because of the risk of development of mutational resistance. PMID- 2327762 TI - Multiple-dose pharmacokinetics of ofloxacin in serum, saliva, and skin blister fluid of healthy volunteers. AB - The pharmacokinetics of ofloxacin were determined in six healthy volunteers after oral administration of 200 mg twice daily for 3.5 days. To study the pharmacokinetic behavior at the target site in bacterial infection of the skin, drug concentrations were determined in suction blister fluid (SBF) and cantharides blister fluid (CBF), as well as in serum and saliva. Ofloxacin was measured by a high-performance liquid chromatographic assay. Ofloxacin concentrations in saliva amounted to 61 +/- 3% of levels in serum. After the final dose, ofloxacin concentrations in blister fluid and serum declined in parallel. Terminal half-lives of ofloxacin in blister fluids (SBF, 7.0 h; CBF, 6.3 h) were in accordance with serum half-life (6.6 h). Favorable penetration into the skin is suggested by high area under the concentration-time curve ratios for blister fluid and serum (CBF, 1.1; SBF, 1.3). During repeated ofloxacin intake, drug levels in SBF and CBF at 12 h amounted to 0.94 and 1.10 micrograms/ml. Thus, ofloxacin levels in the skin are well above the MIC for 90% of strains tested for, e.g., Staphylococcus aureus, Staphylococcus epidermidis, Neisseria gonorrhoeae, and various members of the family Enterobacteriaceae. This should also hold true with respect to other tissues. PMID- 2327763 TI - Pharmacokinetics of a novel quinolone, AT-4140, in animals. AB - The pharmacokinetics of 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(cis-3,5 dimethyl-1- piperazinyl)-4-oxoquinoline-3-carboxylic acid (AT-4140) in experimental animals given a single oral dose of 5 mg/kg were studied. The mean peak levels of AT-4140 in plasma of mice, rats, dogs, and monkeys were 0.25, 0.50, 1.14, and 0.49 micrograms/ml, respectively, with mean elimination half lives of 5.0, 3.8, 8.0, and 11.7 h, respectively. The oral bioavailability of AT 4140 calculated from the ratio of the areas under the concentration-time curve after oral and intravenous administration was 77% in dogs. The levels of AT-4140 in tissue in mice and rats were 1 to 11 times higher than the levels in plasma and 4 to 9 times higher than those of ciprofloxacin in mice. The mean 24-h biliary recovery of AT-4140 in rats was 5.6% of the dose and became 21.3% after beta-glucuronidase treatment. The mean 48-h urinary recoveries of AT-4140 in mice, rats, dogs, and monkeys were 6.7, 12.9, 8.6, and 12.7%, respectively, of the dose and were 7.8, 16.3, 8.9, and 18.9%, respectively, after beta glucuronidase treatment. The pharmacokinetics of AT-4140 may be characterized by its good tissue penetration and its long half-life in plasma and tissues. PMID- 2327764 TI - Significance of "extravascular" protein binding for antimicrobial pharmacodynamics in an in vitro capillary model of infection. AB - The effect of protein binding in an "extravascular" space on antimicrobial pharmacodynamics was studied in an in vitro capillary model of infection. Simulated 500-mg oral doses of dicloxacillin (approximately 96% bound) or cephalexin (less than 5% bound) were administered every 6 h for four doses. A 10 fold-higher dose of dicloxacillin was also studied to determine the effect of drug concentration on the reduction of bacterial killing in the presence of protein. Staphylococcus aureus ATCC 25923 was inoculated into peripheral chambers filled with either Mueller-Hinton broth or Mueller-Hinton broth plus 25% human serum. Serial samples for bacterial counts were collected over 24 h. The presence of serum in the chambers significantly reduced bacterial killing by dicloxacillin but not by cephalexin during the first 6 h (two-way analysis of variance, F = 6.04, P less than 0.05) but not at 24 h. Reduction of dicloxacillin activity in serum-containing chambers persisted with the higher dose. These data suggest that despite attaining higher total drug concentrations in protein-containing extravascular spaces with highly bound drugs, protein binding reduces bactericidal activity during the early stages of treatment in this model. PMID- 2327765 TI - In vitro activity of Ro 23-9424, a dual-action cephalosporin, compared with activities of other antibiotics. AB - The in vitro activity of Ro 23-9424, which is desacetyl-cefotaxime linked to fleroxacin, was compared with the activities of cefotaxime, desacetyl-cefotaxime, fleroxacin, ofloxacin, and ciprofloxacin. It inhibited the majority of members of the family Enterobacteriaceae, except for some Serratia marcescens, Citrobacter freundii, and Enterobacter cloacae strains, at less than or equal to 0.25 microgram/ml and had an MIC for 90% of strains tested (MIC90) of 8 micrograms/ml against Pseudomonas aeruginosa. Most group A, B, C, and G streptococci and Streptococcus pneumoniae were inhibited at less than or equal to 0.25 microgram/ml. Ninety percent of the staphylococci were inhibited at less than or equal to 4 micrograms/ml, except for some methicillin-resistant Staphylococcus aureus isolates. The MIC90S of Ro 23-9424 for Enterococcus faecalis and Listeria monocytogenes were greater than or equal to 16 micrograms/ml. Ninety percent of Clostridium perfringens isolates were inhibited by less than or equal to 2 micrograms/ml, whereas Bacteroides fragilis had an MIC90 of 32 micrograms/ml. There was a minimal inoculum size effect. The MICs and MBCs were either identical or within a twofold dilution. The MICs of Ro 23-9424 for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, and Staphylococcus aureus increased 16- to 128 fold after 2 weeks of transfer in the presence of Ro 23-9424, showing that the presence of two agents does not prevent resistance. PMID- 2327766 TI - Phase I study of single-dose BMY-28100, a new oral cephalosporin. AB - The objective of this Phase I study was to evaluate the safety, tolerance, and pharmacokinetics of BMY-28100 in 36 male subjects after the administration of single oral doses of 250, 500, and 1,000 mg. The subjects were divided into groups of 12 per dose group. All subjects completed the study, and BMY-28100 was well tolerated at all doses. The maximum concentration of the drug in plasma ranged from 6.2 to 17.7 micrograms/ml for the 250- and 1,000-mg doses, respectively, and the area under the curve increased in a dose-proportional manner. The elimination half-life and renal clearance averages were 1.2 h and 200 ml/min, respectively. The values for renal clearance suggest that BMY-28100 is excreted by glomerular filtration and tubular secretion. Mean concentrations of the drug in urine were highest during the first 4 h after the doses and ranged from 175 to 658 micrograms/ml following the 250- and 1,000-mg doses, respectively. The mean urinary recovery ranged from 57 to 70% of the dose. The results from this Phase I study indicate that BMY-28100 is well tolerated and exhibits linear pharmacokinetics. PMID- 2327767 TI - Influence of clavulanic acid on the activity of amoxicillin against an experimental Streptococcus pneumoniae-Staphylococcus aureus mixed respiratory infection. AB - An experimental respiratory infection caused by Streptococcus pneumoniae was established in weanling rats by intrabronchial instillation. Treatment of this infection with amoxicillin rapidly eliminated the pneumococci from the lung tissue. A beta-lactamase-producing strain of Staphylococcus aureus, when inoculated in a similar manner, did not persist adequately in the lungs long enough to permit a reasonable assessment of the therapy, but staphylococcal survival was extended in the lungs of rats infected 24 h previously with S. pneumoniae. Amoxicillin therapy was relatively ineffective against the pneumococci in this polymicrobial infection and had no effect on the growth of S. aureus. In contrast, amoxicillin-clavulanic acid eliminated the pneumococci from the lung tissue and brought about a reduction in the numbers of staphylococci. The data illustrate the utility of this model for the study of polymicrobial lung infections and demonstrate the role of amoxicillin-clavulanic acid in the treatment of polymicrobial infections involving beta-lactamase-producing bacteria. PMID- 2327768 TI - Ofloxacin versus co-trimoxazole for prevention of infection in neutropenic patients following cytotoxic chemotherapy. AB - The efficacy of ofloxacin in preventing infection in neutropenic patients following cytotoxic chemotherapy was evaluated and was compared with that of co trimoxazole. A total of 102 patients with hematological malignancies were randomly selected to receive either co-trimoxazole or ofloxacin. All patients were monitored for compliance, occurrence of infection, and drug-related side effects. A surveillance culture of a rectal swab was performed regularly. A total of 25 of the 52 patients (48%) who received co-trimoxazole and 11 of the 50 patients (22%) who received ofloxacin developed fever during the study period (P less than 0.025). Gram-negative bacteremia occurred in nine patients in the co trimoxazole group (17%) but in only one patient (2%) in the ofloxacin group (P less than 0.05). No patient in either group had documented gram-positive bacterial or Pneumocystis carinii infection. Poor performance status was the only identifiable factor associated with an increased incidence of bacteremia. The surveillance study showed that significantly fewer bacterial strains were resistant to ofloxacin than to co-trimoxazole and that acquisition of resistance to co-trimoxazole was more commonly observed than was acquisition of resistance to ofloxacin. Significantly more patients had skin rashes following co trimoxazole than ofloxacin treatment (P less than 0.05). Ofloxacin was superior to co-trimoxazole in preventing infection in this population of neutropenic patients. PMID- 2327769 TI - Molecular epidemiology of TEM-3 (CTX-1) beta-lactamase. AB - A total of 33 clinical isolates encoding TEM-3 (CTX-1) from four French hospitals were studied. The strains belonged to seven species, Klebsiella pneumoniae (n = 24), Escherichia coli (n = 3), Serratia marcescens (n = 2), Citrobacter freundii (n = 1), Enterobacter aerogenes (n = 1), Enterobacter cloacae (n = 1), and Klebsiella oxytoca (n = 1). All the strains harbored an Inc7 or M self transferable plasmid with a size of approximately 85 kilobases. The plasmids had closely related EcoRI, HincII, HindIII, and PvuII restriction endonuclease generated patterns and conferred resistance to all beta-lactams, except cephamycins and imipenem; to tetracycline, because of the presence of the genes blatem-3 and tetC, respectively, as determined by hybridization with specific probes; and to sulfonamide. Depending on the presence or absence and level of expression of the genes aacA4, aadA, and dfrI and of insertion element IS15, four types of plasmids could be distinguished. Plasmid pCFF04, the prototype plasmid encoding TEM-3, was widespread and appeared, by Southern hybridization, as the progenitor of the other types of replicons. The plasmid epidemic responsible for dissemination of TEM-3 in clinical isolates of members of the family Enterobacteriaceae may have originated in S. marcescens since pCFF04 was first detected in this species. PMID- 2327770 TI - Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis. AB - The efficacy of a new class of drugs for Pneumocystis carinii pneumonitis was demonstrated. 566C80, a hydroxynaphthoquinone, administered orally in a dose of greater than or equal to 100 mg/kg of body weight per day prophylactically prevented P. carinii pneumonitis in 90% or more of rats, while all untreated control animals developed pneumonitis. When 566C80 (100 mg/kg per day) was administered for 3 weeks after P. carinii pneumonitis was established, therapy was totally effective and all of the untreated controls had progressive P. carinii pneumonitis. A dose of 566C80 of between 25 and 50 mg/kg per day protected 50% of the rats from P. carinii pneumonitis, and a dose of between 50 and 100 mg/kg per day cured 50% of those treated for P. carinii pneumonitis. Both prophylaxis and treatment with 566C80 were at least as effective as with trimethoprim-sulfamethoxazole. Animals maintained on immunosuppression after completion of treatment remained free of P. carinii, suggesting a killing effect. Clearance of P. carinii was associated with levels of 60 micrograms or more of 566C80 per ml of plasma. This hydroxynaphthoquinone offers promise as an anti-P. carinii drug. PMID- 2327771 TI - Pharmacokinetics and inflammatory fluid penetration of cefpodoxime proxetil in volunteers. AB - The pharmacokinetics of cefpodoxime were determined after a single oral dose of 261 mg of cefpodoxime proxetil, equivalent to 200 mg of cefpodoxime, was given to each of six healthy male volunteers. Concentrations in serum, urine, and cantharidin-induced inflammatory fluid were measured by a microbiological assay. The mean peak level in plasma was 2.1 micrograms/ml, attained at a mean time of 2.9 h. The mean half-life of elimination from serum was 2.2 h. The inflammatory exudate was penetrated moderately rapidly, the mean peak level being 1.7 micrograms/ml at 3.5 h. The mean percent penetration of the inflammatory exudate was 103.7. The mean 24-h urine recovery of cefpodoxime was 32.2%. This study suggests that cefpodoxime proxetil taken once or twice daily will be sufficient to treat urinary or systemic infections caused by susceptible pathogens. PMID- 2327772 TI - Pentoxifylline in amphotericin B toxicity rat model. AB - The mechanism of acute nephrotoxicity following the administration of amphotericin B (AmpB) remains unclear despite a number of studies describing hypermagnesuria, hyperkaluria, and hemodynamic changes. The present experiments attempted to elucidate the mechanism by using a novel hemorheologic probe, pentoxifylline (PTX). Acute studies were performed with rats given single intravenous doses of AmpB (1 mg/kg of body weight) with or without intraperitoneal PTX (45 mg/kg). Renal function, assessed by inulin clearance (CLIN) and electrolyte handling, and morphology were compared with those of controls given sterile water and PTX. A significant decrease in CLIN not observed in rats given AmpB and PTX or in the controls was found in rats given AmpB. Electrolyte handling was not different among groups. Whereas pronounced (3 and 4+ on a scale of mild to significant [1+ to 4+]) vascular congestion was found in rats given AmpB, rats coadministered PTX had mild (1 and 2+) medullary and glomerular vascular congestion. In chronic studies, intravenous AmpB (1 mg/kg per day) or sterile water was coadministered with intraperitoneal PTX (45 mg/kg every 12 h) or saline for 10 days. Mean CLIN of rats coadministered AmpB and PTX was not significantly different from that of PTX control rats (1.61 +/- 0.19 versus 1.31 +/- 0.29 ml/min per g of kidney weight). A 46% decline in CLIN was found in rats treated with AmpB and saline (P less than 0.05). Renal sodium and potassium excretions were increased in both AmpB-treated groups compared with controls. Coupled with histologic evidence of the acute studies, these data suggest that the benefit of PTX in the prevention of AmpB-induced nephrotoxicity is, in part, due to vascular decongestion. PMID- 2327773 TI - Efficacy of ofloxacin in experimental Staphylococcus aureus endocarditis. AB - The efficacy of ofloxacin was compared with that of vancomycin in the therapy of experimental Staphylococcus aureus endocarditis. Rabbits infected with either a methicillin-susceptible (MSSA-1199) or a methicillin-resistant (MRSA-494) test strain were treated with ofloxacin (20 mg/kg of body weight every 8 h) or vancomycin (17.5 mg/kg of body weight every 6 h) for 4 days. The antimicrobial agents were found to be equally effective in clearing bacteremia and in reducing bacterial counts in vegetations and in renal and splenic tissue of animals infected with either test strain. The drugs were of equal efficacy in curing MRSA 494 endocarditis. No resistance to ofloxacin emerged in either test strain during therapy. We conclude that in this model ofloxacin is as efficacious as vancomycin and that, unlike for other fluoroquinolones we have evaluated, resistance to the drug does not develop during therapy of this serious S. aureus infection. PMID- 2327774 TI - Genetic basis of tetracycline resistance in urogenital bacteria. AB - The distributions of the nucleotide sequences related to the tetracycline resistance determinants Tet K, Tet L, Tet M, and Tet O were studied by dot blot hybridization with randomly chosen clinical urogenital tract isolates of viridans group streptococci, Streptococcus agalactiae, Enterococcus faecalis, Gardnerella vaginalis, Lactobacillus spp., Fusobacterium nucleatum, Peptostreptococcus spp., and Veillonella parvula. Among the Peptostreptococcus spp., 79% of the isolates hybridized with one (64%) or more (36%) of the probes for Tet K (27%), Tet L (30%), Tet M (75%) and Tet O (13%). Of the viridans group streptococci, 82% of the strains hybridized with one (34%) or more (66%) of the four probes. The distribution of the four determinants in this group was as follows: Tet K, 36%; Tet L, 31%; Tet M, 43%; Tet O, 61%. Twenty-nine percent of the enterococci and forty-six percent of the group B streptococci hybridized with the probes; however, the Tet K, Tet L, and Tet O determinants were found in only a few strains, while the Tet M determinant predominated. A total of 29% of the F. nucleatum isolates, 55% of the G. vaginalis isolates, and 26% of the V. parvula isolates hybridized with the Tet M determinant. In contrast, 43% of the Lactobacillus spp. hybridized with the Tet O determinant. The data indicate that tetracycline resistance determinants are common to many of the microorganisms isolated from the urogenital tract. PMID- 2327775 TI - Amikacin pharmacokinetics and suggested dosage modifications for the preterm infant. AB - The pharmacokinetics of amikacin administered intravenously at currently recommended doses (7.5 mg/kg every 12 h for infants with less than 7 days of life; 7.5 mg/kg every 8 h for infants with greater than 7 days of life) were studied in 28 preterm infants weighing less than 2,500 g (mean +/- standard deviation, 1.38 +/- 0.47 kg; postconceptional age, 30.50 +/- 2.86 weeks). The medication was infused over 45 min. Trough and peak serum samples as well as two additional samples were taken at steady state. The results showed a statistically significant inverse relationship between half-life (8.42 +/- 2.55 h) and postconceptional age (P = 0.002) and a direct correlation between total body clearance (0.84 +/- 0.28 ml/min per kg) and postconceptional age (P = 0.02). These pharmacokinetic data were used to calculate a new dosage schedule for preterm infants. The derived intravenous dosage of amikacin for infants of less than 30 weeks of postconceptional age was 9 mg/kg every 18 h. For infants of greater than 30 weeks of postconceptional age, the dosage was 9 mg/kg every 12 h. Peak and trough levels of amikacin in serum that fell within the therapeutic range were compared by using the currently recommended dosage schedule and the dosage schedule derived from our pharmacokinetic data. There was a reduction in the number of peak and trough levels that fell outside the accepted therapeutic range which was not statistically significant. Extension of the dosing interval and a further increase in the dosage may result in further improvement. Based on these data, the current recommendations are inadequate for the preterm infant. Our derived dosage schedule improved but did not eliminate high trough and low peak levels of amikacin in all infants. The current recommendations should be adjusted for the preterm infant. Ongoing therapeutic drug monitoring is essential to tailor the amikacin dosage to the individual patient. PMID- 2327776 TI - Ciprofloxacin therapy of experimental endocarditis caused by methicillin resistant Staphylococcus epidermidis. AB - Ciprofloxacin or rifampin was significantly (P less than 0.05) more effective than vancomycin or the combination of vancomycin plus gentamicin for the treatment of Staphylococcus epidermidis experimental endocarditis. There were no significant differences in efficacy among any of the combinations of antimicrobial agents that included ciprofloxacin or rifampin. One animal treated with rifampin alone and one treated with the combination of vancomycin, rifampin, and gentamicin were found to be infected with rifampin-resistant strains of S. epidermidis during therapy. Resistant subpopulations of S. epidermidis were not detected during therapy with any other antimicrobial agent used alone or in combination. Ciprofloxacin alone or in combination with rifampin was effective therapy against S. epidermidis experimental endocarditis. PMID- 2327777 TI - Uptake and intracellular activity of an optically active ofloxacin isomer in human neutrophils and tissue culture cells. AB - The penetration of an optically active ofloxacin isomer [(-)-ofloxacin] into human neutrophils and different tissue culture cells (HEp-2, McCoy, MDCK, and Vero) was studied and compared with that of ofloxacin by a fluorometric assay. The cellular-to-extracellular-concentration ratios (C/E) of (-)-ofloxacin were always higher than 6, significantly greater than those of ofloxacin at extracellular concentrations of 5 and 10 mg/liter. The penetration of (-) ofloxacin and ofloxacin was doubled when neutrophils were stimulated by phorbol myristate acetate but not affected after ingestion of opsonized Staphylococcus aureus. The C/E ratios of (-)-ofloxacin and ofloxacin for different tissue culture epithelial cells and fibroblasts were lower than those of neutrophils but still higher than 2. Both compounds produced a significant reduction in viable intraphagocytic S. aureus during 3 h of exposure to antimicrobial agents. We conclude that (-)-ofloxacin appears to reach higher intracellular concentrations than ofloxacin, remaining active inside the neutrophils. PMID- 2327778 TI - Cyclobut-A and cyclobut-G, carbocyclic oxetanocin analogs that inhibit the replication of human immunodeficiency virus in T cells and monocytes and macrophages in vitro. AB - Two newly synthesized carbocyclic oxetanocin analogs, (+/-)-9-[(1 beta,2 alpha,3 beta)-2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine (cyclobut-A) and (+/-)-9-[(1 beta,2 alpha,3 beta)-2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine (cyclobut-G) were tested for activity against the infectivity of human immunodeficiency virus (HIV) in vitro. A number of other carbocyclic oxetanocin analogs failed to exert good antiretroviral effects. Both cyclobut-A and cyclobut-G protected CD4+ ATH8 cells against the infectivity and cytopathic effect of HIV type 1 (HIV-1) and suppressed proviral DNA synthesis in ATH8 cells exposed to HIV-1 in vitro at concentrations of 50 to 100 microM. These compounds also inhibited the in vitro infectivity of another human pathogenic retrovirus, HIV-2. Furthermore, both compounds completely suppressed the replication of a monocytotropic strain of HIV 1 in monocytes and macrophages at concentrations as low as 0.5 microM, as assessed by inhibition of HIV-1 p24 gag protein production. We also found that 2' deoxyguanosine readily reversed the antiretroviral activity of cyclobut-G in our system, whereas the activity of cyclobut-A was hardly reversed by 2' deoxyadenosine or 2'-deoxycytidine. We noted, however, that these compounds inhibited the proliferation of peripheral blood mononuclear cells at concentrations of greater than or equal to 100 microM in vitro. Although both cyclobut-A and cyclobut-G appear to have a certain level of in vitro toxicity, our observations may have theoretical and clinical implications in understanding the structure-activity relationships of antiretroviral agents active against HIV. PMID- 2327779 TI - In vitro evaluation of WIN 57273, a new broad-spectrum fluoroquinolone. AB - WIN 57273 is a new fluoroquinolone that has an expanded spectrum of activity against Staphylococcus spp. (MIC for 90% of isolates [MIC90], 0.008 microgram/ml), Enterococcus faecalis (MIC90, 0.06 microgram/ml), Bacillus spp. (MIC90, 0.03 micrograms/ml), Listeria monocytogenes (MIC90, 0.06 microgram/ml), Streptococcus spp. (MIC90, 0.03 microgram/ml), and Bacteroides fragilis group strains (MIC90, 0.5 microgram/ml). Like other fluoroquinolone compounds, WIN 57273 was active against members of the family Enterobacteriaceae (97% of strains inhibited by less than or equal to 2 micrograms/ml), Haemophilus, Branhamella, and Neisseria strains (100% susceptible), Acinetobacter spp. (100% susceptible), and Pseudomonas aeruginosa (68% susceptible). We observed that WIN 57273 was very active against cephalosporin- or aminoglycoside-resistant gram-negative strains but shared cross-resistance with other fluoroquinolones. Increasing inoculum concentrations had minimal effects on WIN 57273 MICs, and the drug was considered to be bactericidal based on reference MBC and kill curve analyses. Unlike most previously studied drugs in this class, WIN 57273 had increased activity (three- to fourfold) at low pH. Rates of mutation to WIN 57273 resistance at eight times its MIC were in the range of 5.6 x 10(-8) to greater than 1.4 x 10(-9). This new compound possesses a wide potential spectrum of use, and it should be evaluated further by in vitro and in vivo studies. PMID- 2327780 TI - Successful treatment using gentamicin liposomes of Salmonella dublin infections in mice. AB - Gentamicin entrapped within stable multilamellar liposomes was used to treat mice after they were infected per os with Salmonella dublin. Of 10 mice, 8 survived after a single intravenous (i.v.) injection of 2 mg of gentamicin liposomes per kg compared with 0 of 10 treated with the same amount of free gentamicin. All mice survived after treatment with a single i.v. or intraperitoneal injection of 20 mg of gentamicin liposomes per kg, whereas that dose of free drug was completely ineffective and caused neuromuscular paralysis when injected rapidly i.v. In mice treated with gentamicin liposomes, there was a steady decrease in the number of salmonellae in spleens for 2 weeks after treatment. High concentrations of gentamicin were present in the spleen for at least 10 days after treatment. Although gentamicin was not detected in the mesenteric lymph nodes of mice treated with gentamicin liposomes, bacterial counts in the nodes also decreased over time. Small numbers of bacteria remained viable in the mesenteric lymph nodes and Peyer's patches but not in the spleens of mice treated with 20 to 80 mg/kg. Mice treated with doses of gentamicin liposomes as high as 80 mg/kg showed only a transient increase in blood urea nitrogen and no rise in serum creatinine. These results confirm that gentamicin in liposomes is less toxic in mice than is free gentamicin and is extremely effective therapy for disseminated Salmonella infections in mice. PMID- 2327781 TI - Vancomycin resistance is encoded on a pheromone response plasmid in Enterococcus faecium 228. AB - In Enterococcus faecium 228, vancomycin resistance is encoded on a 55-kilobase conjugative plasmid, pHKK100. This plasmid was transferred with high frequency into susceptible strains of Enterococcus faecalis and conferred responses to pheromones produced by E. faecalis and Streptococcus sanguis. pHKK100 is the first plasmid described that mediates both vancomycin resistance and pheromone response. PMID- 2327782 TI - Identification of a group of Haemophilus influenzae penicillin-binding proteins that may have complementary physiological roles. AB - [35S]penicillin bound to different Haemophilus influenzae proteins in assays performed at 20, 37, or 42 degrees C. Penicillin-binding proteins 3a, 3b, 4, and 4' formed a group characterized by their affinity for moxalactam, cefotaxime, and piperacillin. Penicillin-binding protein 4' showed specific properties that may reflect its complementary role in septation. PMID- 2327783 TI - Bactericidal activities of various antimicrobial agents against human and animal isolates of Mycobacterium paratuberculosis. AB - The MICs and MBCs of various antimicrobial agents for strains of Mycobacterium paratuberculosis isolated from animal and human sources were evaluated. The MICs and MBCs of rifabutin, ciprofloxacin, ethambutol, clofazimine, streptomycin, cefazolin, and amikacin were found to be well below therapeutic levels in serum and tissue. PMID- 2327784 TI - In vitro activities of tosufloxacin, temafloxacin, and A-56620 against pathogens of diarrhea. AB - Tosufloxacin (A-60969 HCl), a new quinolone with broad activity against gram positive and anaerobic organisms, was compared in vitro with other quinolones against bacterial pathogens of diarrhea. Tosufloxacin was the most active agent against Salmonella spp., Shigella spp., Campylobacter spp., Aeromonas hydrophila, and Vibrio spp. Temafloxacin (A-62254) also demonstrated good activity against these organisms. PMID- 2327785 TI - In vitro activity of amikacin against Mycobacterium avium. PMID- 2327786 TI - Isolation and structural analysis of three new disialylated oligosaccharides from human milk. AB - Five disialylated oligosaccharides, of which three were new compounds, were isolated from pooled human milk. The isolation procedure included gel filtration and ion-exchange chromatography and the final purification was accomplished by HPLC using a mobile phase containing triethylamine as an ion-pairing reagent. Structural analysis was carried out by chemical analyses, fast atom bombardment mass spectrometry, and 500-MHz NMR spectroscopy. The following new structures were found: (formula; see text). PMID- 2327787 TI - Purification and characterization of human liver phenol-sulfating phenol sulfotransferase. AB - The phenol-sulfating form of phenol sulfotransferase (P-PST) was purified and characterized from human liver cytosol using DEAE-cellulose, Sephacryl S-200, and 3',5'-diphosphoadenosine-agarose affinity chromatography. During the purification procedure, P-PST was resolved from the monoamine-sulfating form of phenol sulfotransferase (M-PST) and dehydroepiandrosterone sulfotransferase, which are also present in human liver cytosol. P-PST activity was purified 560-fold as compared to liver cytosol and the purified enzyme possessed a specific activity of 340 nmol phenol sulfated per minute per milligram protein. Enzymatically active P-PST has an apparent molecular size of 68,000 Da as determined by Sephacryl S-200 chromatography and a subunit molecular weight of 32,000 Da as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that P-PST exists in vivo as a homodimer. Antibodies raised to human platelet M-PST cross-reacted strongly with pure P-PST suggesting the two PSTs are structurally closely related. Two types of P-PST activity have been identified in different human livers by their thermostability and elution during anion-exchange chromatography. Each of the livers examined possessed only one type of P-PST activity. Both types of P-PST were shown to possess the same subunit molecular weight and immunoreactivity, whereas the differences in thermostability of the two P-PST activities appeared to be related to the method of preparation of liver cytosol. Both types of P-PST activity were inhibited to similar extents by incubation with 50 microM N-ethylmaleimide or 5 mM phenylglyoxal. These results suggest that the two types of P-PST in different human livers are very similar and probably represent different allelic forms of the enzyme. PMID- 2327788 TI - The amino acid sequence of a myotoxic phospholipase from the venom of Bothrops asper. AB - A myotoxic, basic phospholipase A2 (pI greater than 9.5) with anticoagulant activity has been purified from the venom of Bothrops asper, and its amino acid sequence determined by automated Edman degradation. It is distinct from the B. asper phospholipase A2 known as myotoxin I [Lomonte, B. and Gutierrez, J. M., 1989, Toxicon 27, 725] but cross-reacts with myotoxin I rabbit antisera, suggesting that the proteins are closely related isoforms. To our knowledge, this is the first myotoxic phospholipase to be sequenced that lacks presynaptic neurotoxicity (iv LD50 approximately equal to 8 micrograms/g in mice). The protein appears to exist as a monomer, contains 122 amino acids, and fits with subgroup IIA of other sequenced phospholipase A2 molecules. Its primary sequence shows greatest identity with ammodytoxin B (67%), a phospholipase A2 presynaptic neurotoxin from Vipera ammodytes ammodytes venom. Hydropathy profiles of B. asper phospholipase and the ammodytoxins also show great similarities. In contrast, even though the amino acid sequence identities between B. asper phospholipase and the basic subunit of crotoxin remain high (64%), their hydropathy profiles differ substantially. Domains and residues that may be responsible for neurotoxicity are discussed. PMID- 2327789 TI - Elastin metabolism during recovery from impaired crosslink formation. AB - Accelerated proteolysis of tropoelastin and elastin occurs in the arteries of chicks rendered nutritionally copper-deficient. The process results in part from decreased elastin crosslinking. Repletion of copper-deficient chicks with copper causes a deposition of elastin that is proteinase resistant. Resistance to proteolysis is conferred within 48 h of dietary copper repletion. Deposition of aorta elastin to near normal values occurs after 3-4 days in copper-repleted chicks. Moreover, elastolysis was enhanced when the content of dehydrolysinonorleucine in elastin was abnormally low. The chemical modification of lysyl residue in elastin by citroconylation, however, did not influence the rate of elastolysis. We have shown previously that tropoelastin messenger RNA activity and synthesis are not influenced by dietary copper deprivation (1986, Biochem. J. 236, 17-23). Rather, as demonstrated herein, the decrease in elastin content in arteries of copper-deficient birds appears to be more the result of enhanced degradation. Restoration of normal crosslinking restores deposition and imparts resistance to elastolysis. Moreover, serum appears to be a good source of elastolytic proteinases when the elastin substrate is partially or abnormally crosslinked. PMID- 2327790 TI - Purification and characterization of a large, tryptic fragment of human thyroid peroxidase with high catalytic activity. AB - Thyroid peroxidase (TPO) was purified from human thyroid tissue, obtained at surgery from patients with Graves' disease, by a procedure similar to one that we had previously used for the purification of porcine TPO. The membrane-bound enzyme was solubilized by treatment of the thyroid particulate fraction with trypsin plus detergent. After precipitation with ammonium sulfate, the enzyme was purified by a series of column treatments, including ion-exchange chromatography on DEAE-cellulose, gel filtration through Bio-Gel P-100, and hydroxylapatite chromatography. Although a high degree of purification was achieved, the finally isolated product was considerably more heterogeneous than the TPO obtained from porcine thyroids. Several pools of active enzyme differing in values for A412/A280 and in specific activity were collected. Gel electrophoresis was performed under native, denaturing [sodium dodecyl sulfate (SDS)] and denaturing plus reducing conditions. Native gel electrophoresis indicated that the active enzyme (93 kDa) was heavily contaminated with an inactive 60-kDa fragment, which we were unable to remove by HPLC. The inactive fragment was highly antigenic when tested on immunoblots with an antibody to TPO. The presence of the inactive fragment greatly reduced values for A412/A280 in the finally purified human TPO. Two of the pools, with A412/A280 values of 0.159 and 0.273, were used for further testing. Catalytic activity was very similar in these two pools when measured on the basis of heme content by several different assays. Moreover, the specific activities of both, based on heme content, were very similar to those observed with a porcine TPO preparation with A412/A280 = 0.48. These findings indicate that the inactive 60-kDa fragment most likely did not contain heme. On SDS polyacrylamide gel electrophoresis under reducing conditions, the 60-kDa fragment completely disappeared and was replaced by a 36- and a 24-kDa component. Amino terminal sequence information obtained on these components indicated that the 24 kDa component represents the amino terminal portion of the active 93-kDa fragment, whereas the 36-kDa fragment represents the carboxyl terminal portion. A model is proposed suggesting that the 60-kDa fragment was generated by trypsin cleavage of native TPO at two internal sites within a disulfide loop (res approximately 300 and res 564) and at one further internal site (res 280). In addition, trypsin cleavage is proposed at sites near the amino and carboxyl ends common to both the active 93-kDa and the inactive 60-kDa fragments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2327791 TI - Retinoids affect collagen synthesis through inhibition of ascorbate-induced lipid peroxidation in cultured human dermal fibroblasts. AB - Ascorbate has been shown to stimulate collagen synthesis in cultured human dermal fibroblasts by increasing transcription of the collagen genes. In the present studies, ascorbate stimulates lipid peroxidation at concentrations similar to those necessary to affect collagen synthesis. Molecules which inhibit lipid peroxidation, such as propyl gallate, cobalt chloride, and alpha-naphthol, also inhibit collagen synthesis, suggesting a correlation between the two phenomena. Retinoic acid and some synthetic retinoids have previously been shown to inhibit collagen synthesis in cultured human dermal fibroblasts. In our studies two different retinoids, at similar concentrations, inhibit both ascorbate-stimulated lipid peroxidation and collagen synthesis. Since high concentrations of retinoids were required, the ability of retinoids to inhibit the oxidant effect of ascorbate, and not their receptor-mediated activity, may be responsible for their effect on collagen synthesis. PMID- 2327792 TI - The distribution of glycan structures in individual N-glycosylation sites in animal and plant glycoproteins. AB - Glycopeptides representing each individual N-glycosylation site in six animal and plant glycoproteins (ovoinhibitor and ovotransferrin, orosomucoid, antitrypsin, phaseolin, and phytohemagglutinin) have been isolated and compared by mass spectrometric analysis. Since the isolation step separates each individual peptide regardless of the nature of the glycan attached to it, it is possible to observe the entire spectrum of glycans associated with each site from the mass spectrum of the corresponding glycopeptide. The three glycosylation sites in ovoinhibitor have very similar but not identical glycans; they are significantly different from those observed in the single site of ovotransferrin. The three sites in serum antitrypsin also have quite similar glycans, whereas the five sites in orosomucoid show considerable variation in both the nature and the relative amount of glycans. The two plant glycoproteins each have two sites with very different glycan structures. Except for the first and third glycosylation sites of antitrypsin which were found to have remarkably homogeneous glycans (97 and 90% of a biantennary complex structure), all the individual glycosylation sites contained heterogeneous mixtures of glycan structures. The results support the proposition that each N-linked glycan in a glycoprotein is affected by its unique protein environment to such an extent that each one may be displayed to the processing enzymes as a unique structural entity. On the basis of a limited number of observations of the glycan interfering with chymotryptic but not tryptic cleavage in the proximity of the glycan attachment site, it is proposed that hydrophobic interactions between the protein and the glycan may be involved in the conformational modulation of the glycans. PMID- 2327793 TI - The influence of pH on substrate form specificity of phosphoenolpyruvate carboxylase purified from Crassula argentea. AB - Purified phosphoenolpyruvate carboxylase from both the crassulacean acid metabolism plant Crassula argentea and the C4 plant Zea mays was shown by kinetic studies at saturating fixed-varying concentrations of free mg2+ to selectively use the metal-complexed form of phosphoenolpyruvate when assayed at pH 8.0. A similar response to added magnesium at high free phosphoenolpyruvate concentrations was obtained for both enzymes, consistent with the use of the complex as the substrate. Kinetic studies at pH 7.0 indicated that at this pH the total concentration of phosphoenolpyruvate (including both free and metal complexed forms) could be used by the enzyme from C.argentea while the C4 enzyme still utilized the complex. The loss of specificity induced by the decrease in the pH of the assay medium was accompanied by a decrease in the Km of this enzyme for phosphoenolpyruvate whatever the form considered and an increase in Vmax/Km. In contrast, a similar decrease of pH led to an increased Km of the C4 enzyme for phosphoenolpyruvate and a decrease of Vmax/Km. For the enzyme from C. argentea (previously shown to contain an essential arginine at the active site), protection of activity by the different forms of substrate against inactivation by the specific arginyl reagent 2,3-butanedione changes markedly with pH. At pH 8.1, the metal complex is the better protector while at pH 7.0 free phosphoenolpyruvate gives the best protection consistent with the observed kinetic changes in substrate form utilization. The relationship between the enzyme affinity for substrate, substrate specificity, and the requirement for magnesium for substrate turnover is discussed. PMID- 2327794 TI - Biotinidase in the porcine cerebrum. AB - Biotinidase activities found in porcine brains (n = 3) were as follows: cerebrum, 4.4 +/- 0.2 pmol/min per milligram of protein; cerebellum, 7.6 +/- 0.3 pmol/min per milligram of protein; medulla, 2.9 +/- 0.3 pmol/min per milligram of protein. These values are relatively high compared with the activities in rat or guinea pig brains. Subcellular distribution of biotinidase was found mainly in the soluble cytoplasmic fraction (S3), i.e., in the supernatant of 0.32 M sucrose S2 solution after ultracentrifugation at 105,000g for 90 min. This is in contrast to the guinea pig livers, in which the subcellular distribution of biotinidase is mainly found in the microsomal fraction. After a seven-step purification (22,200 fold enrichment), porcine brain biotinidase is identified as a single polypeptide by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis system, and its molecular weight is determined as 68,000 Da. The isoelectric point of the enzyme was 4.3. Sialidase treatment strongly suggests the presence of sialyl residues in this enzyme. Amino acid analysis indicates relatively high hydrophilicity and high content of glycine and serine. The enzyme activity is inhibited by organic mercurials, but not by diisopropylfluorophosphate. Abundant soluble biotinidase in brain cytoplasm may play an important role which has not been discovered yet. PMID- 2327796 TI - Enhanced activity of the tricarboxylate carrier and modification of lipids in hepatic mitochondria from hyperthyroid rats. AB - The effect of hyperthyroidism on the activity of the mitochondrial tricarboxylate carrier has been studied. The activity of this transporting system in liver mitochondria was quantitatively determined by the rate of malate-[14C]citrate exchange using the 1,2,3-benzene-tricarboxylate inhibitor stop technique. It has been found that the rate of citrate uptake is significantly enhanced in liver mitochondria from hyperthyroid rats as compared to that obtained in mitochondria from control rats. Kinetic analysis of the malate-citrate exchange reaction indicates that only the Vmax of this transporting process is enhanced, while there is practically no change in the Km values. Inhibitor titrations with the inhibitor palmitoyl-CoA show that mitochondria from hyperthyroid rats require the same concentrations of inhibitor to produce 100% inhibition of citrate uptake as control mitochondria, suggesting that the amount of functional translocase enzyme present is unaffected. The Arrhenius plot characteristics differ for tricarboxylate carrier activity in mitochondria from hyperthyroid rats as compared with control rats in that the break point of the biphasic plot decreases from 18.1 +/- 1.4 degrees C in controls to 12.9 +/- 1.2 degrees C in hyperthyroid animals. The hepatic mitochondrial lipid composition is altered significantly in hyperthyroid rats; the total cholesterol decreases and the phospholipids increase. The liver mitochondrial phospholipid composition is altered significantly in hyperthyroid rats. In particular negatively charged phospholipid cardiolipin increases by more than 50%. Minor alterations were found in the pattern of fatty acids. The thyroid hormone induced change in the activity of the tricarboxylate carrier can be ascribed either to a general modification of membrane lipid composition which increases the membrane fluidity and in turn the mobility of the carrier or to a more localized change of lipid domain (cardiolipin content) surrounding the carrier molecule in the mitochondrial membrane. PMID- 2327795 TI - Primary and secondary structural analyses of glutathione S-transferase pi from human placenta. AB - The primary structure of glutathione S-transferase (GST) pi from a single human placenta was determined. The structure was established by chemical characterization of tryptic and cyanogen bromide peptides as well as automated sequence analysis of the intact enzyme. The structural analysis indicated that the protein is comprised of 209 amino acid residues and gave no evidence of post translational modifications. The amino acid sequence differed from that of the deduced amino acid sequence determined by nucleotide sequence analysis of a cDNA clone (Kano, T., Sakai, M., and Muramatsu, M., 1987, Cancer Res. 47, 5626-5630) at position 104 which contained both valine and isoleucine whereas the deduced sequence from nucleotide sequence analysis identified only isoleucine at this position. These results demonstrated that in the one individual placenta studied at least two GST pi genes are coexpressed, probably as a result of allelomorphism. Computer assisted consensus sequence evaluation identified a hydrophobic region in GST pi (residues 155-181) that was predicted to be either a buried transmembrane helical region or a signal sequence region. The significance of this hydrophobic region was interpreted in relation to the mode of action of the enzyme especially in regard to the potential involvement of a histidine in the active site mechanism. A comparison of the chemical similarity of five known human GST complete enzyme structures, one of pi, one of mu, two of alpha, and one microsomal, gave evidence that all five enzymes have evolved by a divergent evolutionary process after gene duplication, with the microsomal enzyme representing the most divergent form. PMID- 2327797 TI - Aldehyde-oxidizing enzymes in an adult moth: in vitro study of aldehyde metabolism in Heliothis virescens. AB - The conversion of pheromonal aldehydes to carboxylic acids in vitro in tissue extracts of Heliothis virescens is catalyzed by both aldehyde dehydrogenase and aldehyde oxidase enzymes. The aldehyde-oxidizing activity in antennae, heads, legs, and hemolymph from male and female moths was examined by radiochromatographic and spectroscopic assays. First, the enzymatic activity was measured in the presence or absence of added NAD+ using either (Z)-9-tetradecenal or (Z)-11-hexadecenal as tritiated substrate. Second, substrate specificity was determined spectroscopically by (i) indirect measurement of the AO-released hydrogen peroxide through the coupled AO-horseradish peroxidase reaction and by (ii) direct measurement of the ALDH-produced NADH. Both aldehyde-oxidizing activities were associated with soluble enzymes in the antennal extracts, and these enzymes degraded pheromone and nonpheromonal aldehydes. Both AO and ALDH activities were present in male and female tissues. AO activity was exhibited primarily in the antennal extracts and to a lesser degree in the leg extracts. Moreover, ALDH activity was distributed in the antenna, head, and leg extracts. A vinyl ketone analog of (Z)-11-hexadecenal preferentially inhibited the ALDH activity over the AO activity. PMID- 2327798 TI - Regulation of juvenile hormone esterase gene expression in the tobacco budworm (Heliothis virescens). AB - The tissue distribution, developmental control, and induction of juvenile hormone esterase (JHE) mRNA was examined in Heliothis virescens using an 800-base pair fragment of a JHE cDNA clone. Northern hybridization analysis of poly(A)+RNA from fat body and integument of fifth stadium larvae indicated the presence of a single JHE mRNA species having an estimated length of 3 kilobases. On Day 2 of the fifth stadium (L5D2), basal JHE mRNA levels were 3-fold higher in the integument than the fat body, which correlated with the higher specific activity of the enzyme in the integument at this time. However, JHE mRNA levels in the fat body on Day 4 of the fifth stadium were 9-fold higher than on Day 2, while mRNA levels in the integument remained the same. This endogenous increase in JHE mRNA and activity in the fat body occurred at the time of peak hemolymph JHE activity. JHE mRNA was not detected in third stadium larvae which have very low levels of JHE activity. Treatment of L5D2 larvae with the juvenile hormone mimic epofenonane resulted in a 7- and 14-fold increase in the level of JHE mRNA in the integument and fat body, respectively. The mRNA induced in both tissues was of the same estimated length as the constitutively expressed message. The data indicate that the developmental regulation and induction of JHE can occur at the level of mRNA. There is evidence that the fat body secretes more JHE than does the integument and could be the major source of hemolymph JHE. PMID- 2327799 TI - Quantitation of the hydroxyl radical by reaction with dimethyl sulfoxide. AB - This investigation was conducted to validate the use of dimethyl sulfoxide (DMSO) as a quantitative molecular probe for the generation of hydroxyl radicals (HO.) in aqueous systems. Reaction of HO. with DMSO produces methane sulfinic acid as a primary product, which can be detected by a simple colorimetric assay. To evaluate this method for estimating total HO. production, we studied three model systems, including the Fenton reaction, gamma irradiation of water, and ultraviolet photolysis of hydrogen peroxide, for which the theoretical maximum yield of HO. could be calculated and compared to measured DMSO oxidation. The results confirm that 0.05 to 1 M DMSO may be used to capture nearly all of the expected HO. radicals formed. Thus, methane sulfinic acid production from DMSO holds promise as an easily measured marker for HO. formation in aqueous systems pretreated with DMSO. PMID- 2327800 TI - Detection and characterization of hyperfine-shifted resonances in the proton nuclear magnetic resonance spectrum of Anabaena 7120 ferredoxin at high magnetic fields. AB - This paper presents previously unobserved signals in the 1H NMR spectra of oxidized and reduced [2Fe-2S]-ferredoxin from Anabaena 7120 detected at 400, 500, and 600 MHz. The signals shifted to low field exhibited longitudinal relaxation (T1) values in the range of 100-400 microseconds and line widths in the range of 1-10 kHz (at 400 MHz), and the chemical shifts of all signals showed strong temperature dependence. Although the line widths were smaller at lower magnetic fields, the resolution was better at higher magnetic fields. In the oxidized state, a broad signal was detected at 37 ppm, which corresponds to at least 6 protons, and whose chemical shift exhibits positive temperature dependence. This signal also was found in oxidized ferredoxin reconstituted in 2H2O, which excludes the signal as arising from solvent-exchangeable amide protons. In the reduced state, four signals detected between 90 and 140 ppm exhibited negative temperature dependence. These consisted of two pairs of signals, each pair having one component with half the linewidth of the other. On the basis of their chemical shifts, linewidths, longitudinal relaxation properties, and temperature dependence we assigned these resonances to four of the beta hydrogens of the ligated cysteines. Two solvent-exchangeable hyperfine-shifted signals were found in the reduced state; these are located upfield of the diamagnetic region. The low-field hyperfine resonances of half-reduced ferredoxin in the presence of sodium dithionite showed a self electron transfer exchange rate that was slow on the NMR scale as observed earlier (Chan, T., and Markley, J. L. (1983) Biochemistry 22, 5982-5987), but the exchange rate was accelerated in the presence of methyl viologen. PMID- 2327801 TI - American Nephrology Nurses' Association 21st National Symposium, Washington, D.C. PMID- 2327802 TI - Switching from standard dialysis to rapid high efficiency dialysis with reuse. AB - The chronic outpatient renal unit of Lutheran Hospital Inc. has chosen to become a high-tech hemodialysis unit. We reconstructed our method of administering hemodialysis by instituting high efficiency, kinetic modeling, and reuse programs. Implementing these programs concurrently was a task that we would like to share with ANNA Journal readers. PMID- 2327803 TI - Preparing for inspection: a tool to maximize quality and minimize risk. AB - Self-assessment of a dialysis unit can provide an effective means of improving or assuring the level of quality the unit provides in delivering safe and effective care. A tool for use by facility personnel was developed and is being used in 12 dialysis units within one dialysis company. This tool has been useful in identifying areas of risk and in assisting units in developing and maintaining survey readiness. This article presents the facility tool and describes how it may be used to assist other dialysis facilities in risk management and quality assurance activities. PMID- 2327804 TI - Case management of the anemic patient. Epoetin alfa: focus on patient teaching. AB - Nephrology nurses who are highly involved in the care of dialysis patients receiving Epoetin alfa are frequently responsible for educating and monitoring them as well. The following case study shows one methodology that can be used to accomplish these goals. The article highlights topics and terms for patient teaching, and an interdisciplinary care plan for monitoring Epoetin alfa treatments. PMID- 2327805 TI - ESRD and cardiovascular instability. PMID- 2327806 TI - The end of armchair politics. PMID- 2327807 TI - Separation and identification of immunosuppressive factors in human semen. PMID- 2327808 TI - Quantification and localization of wheat germ agglutinin receptor on human sperm membrane and male fertility and infertility. PMID- 2327809 TI - Hypo-osmotic swelling test: analysis of prevasectomy ejaculates. AB - The hypo-osmotic swelling (HOS) test was applied to 1,890 ejaculates obtained from previously fertile men who subsequently underwent a vasectomy. Less than 3% of the ejaculates produced an abnormal HOS test (less than 50% swelling), and more than 95% were normal (greater than or equal to 60% swelling). The sperm concentration and motility data were similar to those obtained by other investigators with prevasectomy ejaculates. Statistically significant but low correlation coefficients were present between the HOS test and these other sperm variables. On the assumption that the large majority of these men were fertile when the ejaculates were produced, the results support the contention that fertility is usually associated with normal or, occasionally, equivocal values in the HOS test. PMID- 2327810 TI - Differences in lipoprotein composition between heads and tails of human sperm: an infrared spectroscopy study. AB - Human spermatozoa and their fractions (heads and tails) have been studied by infrared spectroscopy. Protein conformation in isolated human spermatozoa heads, although predominantly of the alpha helix or random coil type, has a significant proportion of antiparallel B structure. Spectra of isolated spermatozoa tails show that proteins exist in this fraction preponderantly in pleated-sheet conformation (parallel and antiparallel). The quantity and type of lipids seem to be drastically different between heads and tails of spermatozoa. Head lipids are scarce and difficult to extract, and they are apparently tightly bound to proteins, highly unsaturated, and rich in free hydroxyl and carboxyl groups. Tail lipids are more abundant and more easily extractable. Head phospholipids are probably phosphatidylcholine, cephalins, and inositols, and tail phospholipids are preponderantly plasmalogen-type lecithins and sphingomyelins. The presence of specific infrared bands points to the existence in tails of important amounts of sulfur compounds, probably sulfolipids or sulfoglycolipids. PMID- 2327811 TI - Biological functions of mouse seminal vesicle fluid. I. Suppression of blastogenic responses of lymphocytes. AB - The effect of mouse seminal vesicle fluid (SVF) on blastogenic response of splenocytes to mitogens was investigated. SVF significantly suppressed blastogenic response of splenocytes to concanavalin A and phytohemagglutinin in a dose-dependent manner, but blastogenic response to lipopolysaccharide was suppressed only at low, although significant, levels, even at high concentrations of SVF. Extensive dialysis did not reduce the capacity of SVF to inhibit blastogenesis of splenocytes. For elucidation of the mechanisms of suppression of blastogenic response, interleukin-2 (IL-2)-dependent cells were cultured in the presence of IL-2 and various concentrations of SVF. The presence of SVF did not inhibit the proliferative response of IL-2-dependent cells to IL-2. These results suggest that the suppression of blastogenic response of T lymphocytes to mitogens in seminal plasma is caused by an undialyzable component (or components) derived from seminal vesicle and is attributable to the alteration of receptors for mitogens or of IL-2 receptors that are expressed on stimulation by mitogens. PMID- 2327813 TI - Adoptive transfer of murine autoimmune orchitis with sperm-specific T lymphoblasts. AB - A protocol was successfully developed for reproducibly transferring experimental autoimmune orchitis (EAO) to naive recipient mice with sperm-specific T lymphoblasts. Cell donors were Balb/c mice immunized about 12 days earlier with homologous epididymal sperm capacitated in vitro with complete Freund's adjuvant. Draining lymph node cells were collected and subjected to a second challenge with the same sperm antigen in vitro. Sperm-specific T lymphoblasts were isolated on Percoll density gradients and propagated in the presence of interleukin-2 for 3 days and then were transferred intraperitoneally to naive recipients. As few as 3 x 10(6) sperm-specific T lymphoblasts were able to transfer EAO, which began on day 7 as infiltration of lymphocytes and macrophages and on days 14 to 21 developed to degenerative changes of spermatids and exfoliation of germinal epithelium. These pathologic alterations resemble a delayed type of hypersensitivity. The results show that sensitized T lymphoblasts can mediate an antigen-specific, mononuclear cell-invasive lesion in autoimmune orchitis. PMID- 2327812 TI - Immunosuppressive activity and polyamine levels of seminal plasma in azo ospermic, oligospermic, and normospermic men. AB - Seventy specimens of human seminal plasma obtained from azo-ospermic, oligospermic, and normospermic men were tested for immunosuppressive activity on normal donor lymphocytes. Spermine and spermidine levels in acidic extracts were determined in 32 specimens of seminal plasma from the three groups. The original seminal plasma as well as the neutralized spermine extracts were examined for their effect on the functional activity of the lymphocytes. Seminal plasma obtained from the normospermic and oligospermic semen showed significant immunosuppressive activity, whereas no immunosuppressive activity was induced by seminal plasma from azo-ospermic semen. The latter finding was in accordance with the low spermine levels in azo-ospermic semen, which were about 50% of those found in normospermic and oligospermic seman. Acidic extraction of the seminal plasma of azo-ospermic origin resulted in an increase in spermine levels and also in immunosuppressive activity, demonstrating that in azo-ospermic men spermine is bound probably to a protein and is released after acidification, exerting its immunosuppressive activity only when unbound. PMID- 2327815 TI - Cryogenic preservation of low-quality human semen. AB - The article describes the technical strategies for clinical cryogenic preservation of low-quality human semen. To compensate for sperm dilution resulting from the use of a cryogenic medium, ejaculated semen was concentrated before freezing by means of continuous-step density gradient centrifugation. Freezing was simplified by employing the carbon dioxide pellet method with KS-II cryogenic medium, which contains Pluronic F-68, a nonionic detergent, to solubilize egg yolk (a major cryogenic protectant). Semen of less than 50% motility (n = 23) was processed and then cryogenically preserved. Sperm concentration was increased by a factor of 1.8 +/- 0.96 (n = 23). Sperm motility was improved from 35.9% +/- 13.9% to 69.4% +/- 10.8%. Even after thawing 59.4% +/ 17.5% motility remained, with a mean survival rate of 85% +/- 14%. The concentration of sperm and improved sperm motility by the use of the continuous step density gradient and the high survival rate ensured by the carbon dioxide pellet method with KS-II cryogenic medium compensated for the lowering of sperm quality during cryogenic preservation. PMID- 2327814 TI - Improvement of semen characteristics after surgical repair of bilateral testicular varicocele as compared to unilateral varicocele patients. AB - The operative treatment for surgical repair of bilateral testicular varicoceles was evaluated in terms of the improvement achieved in the sperm density and percentage progressive motile sperm. These parameters were compared for 27 cases of bilateral varicocele diagnosed by palpation and subjected to bilateral high ligation of the internal spermatic vein and for 40 cases of left unilateral testicular varicocele. There were no significant differences in preoperative values (such as sperm density; progressive motile sperm; serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone; and Johnson's score count) between the bilateral and unilateral testicular varicocele groups. The improvement in postoperative sperm density in the cases with bilateral testicular varicocele was apparently less satisfactory than in the cases with testicular varicocele only on the left side. PMID- 2327816 TI - Improved semen qualities after continuous-step density gradient centrifugation: application to artificial insemination and pregnancy outcome. AB - For increasing sperm fertilizability in artificial insemination, it is effective to concentrate progressively motile sperm from whole ejaculate. We developed the continuous-step density gradient for the selective concentration of progressively motile sperm. The present procedure was applied to intrauterine artificial insemination. Infertile couples (n = 152) whose diagnoses involved oligoasthenospermia, cervical factor, and unexplained infertility were selected for artificial insemination with washed and concentrated sperm. Successful pregnancies (47) were obtained, with an overall pregnancy rate of 31% in the program. Sperm processing by this procedure improved pregnancy rates in couples with the sole diagnosis of oligoasthenospermia or cervical factor. In the patients in whom other fertility problems coexisted, however, it was essential to treat female fertility problems. Continuous-step density gradient centrifugation is effective in increasing the pregnancy rate in artificial insemination. PMID- 2327817 TI - Human sperm cryobiological characteristics: comparative cryopreservation techniques. PMID- 2327818 TI - Wheat germ agglutinin (WGA) receptors on human sperm membrane and male infertility. PMID- 2327819 TI - Adoptive transfer of murine autoimmune orchitis with sperm-specific T lymphoblasts. PMID- 2327820 TI - Andrological parameters in men with high sperm counts and possible correlation with age. AB - Two hundred eighty six human semen samples with sperm counts above 200 million/ml, were divided into 3 groups according to semen volume: (1) less than 1 ml (low), (2) 1 ml-5 ml (normal), and (3) greater than or equal to 6 ml (high). Each group was examined for routine andrological parameters. Also examined was a possible correlation between sperm counts, semen volumes, and ages of patients. The quality of motility (percent and grade) and viability of sperm were generally lowest in specimens with a volume below 1 ml and highest in those of normal volume. Proportions of morphological normality exhibited a similar trend, lacking, however, statistical significance. The mean fructose content of low volume semen was significantly decreased in comparison with those of normal volume. Patients with low-volume semen and sperm counts above 200 million/ml were older than those with similar sperm counts and normal volume. The mean ages of all patients with high sperm counts of semen were higher than of those with lower sperm counts. It was assumed that in contradiction to specimens with high sperm counts and low volume, those whose volumes range from 1 ml-5 ml should be considered normal with respect to motility, viability, and morphological normality. PMID- 2327821 TI - Damaging effects of cisplatin on mouse spermatozoa. AB - The effect of cis-diamminedichloroplatinum (cisplatin: CDDP) on mouse spermatozoa was evaluated quantitatively by means of equilibrium sedimentation in Percoll. CDDP was administered subcutaneously at doses of 1, 3, and 10 mg/kg/week for 5 weeks. After different periods (1, 3, and 10 weeks) without CDDP, the quality of epididymal sperm was evaluated by sperm count, motility, morphology of sperm, and the apparent density of sperm. At 10 mg/kg dose, about 80% mortality occurred during the administration period. There were no sperm even 10 weeks after discontinuing CDDP. With the 3 mg/kg dose, sperm count, motility, and normal morphology of sperm declined after 1 and 5 weeks, but recovered to the control level after 10 weeks. The sperm distribution profiles in the Percoll gradient were quite different among the groups. The control sperm showed two separated peaks in the gradient, whereas the peak of sperm at 1 and 3 mg/kg were shifted forward to lighter apparent density. CDDP causes a reduction in sperm apparent density and impairs semen quality in mice. PMID- 2327822 TI - Ficoll gradient isolation of immature sperm of high purity and intactness from goat epididymis. AB - An improved Ficoll density gradient centrifugation method has been described for the isolation of goat caput-epididymal immature spermatozoa of a high purity and intactness. The method consists of layering freshly extracted sperm suspension on the top of a Ficoll gradient comprising 2.5 ml each of 2%, 4%, 6%, and 8% Ficoll 400 in a modified Ringer's solution and centrifugation at 300 g for 3 min in a swing bucket table centrifuge. Spermatozoa, free from fat globules and blood cells, sedimented at the bottom of the 8% Ficoll layer. The plasma membrane of the isolated cells showed a high degree of intactness (approximately 96%) as assessed by lactic dehydrogenase marker enzyme and ethidium bromide-fluorescence methods. PMID- 2327823 TI - Effects of kallikrein on sperm motility, capillary tube test, and pregnancy rate in an AIH program. AB - From 1984 to 1986, 172 couples were enrolled in an artificial insemination homologous (AIH) program, because of negative postcoital test, fair PT, positive PT with unexplained infertility, and impotentia coeundi. Patients were randomly assigned to the following procedures: AIH with native semen (N, n = 68), washed sperm (V, n = 50), semen mixed with kallikrein (K, 5 IE/ml semen, n = 45), and timed intercourse. The overall pregnancy rate (PR) was 22% per couple (13% inseminations, 9% spontaneous). PR from insemination (spontaneous) was 13% (8), 13% (13), 23% (0) in PT negative, fair, and positive patients, respectively, and 18% (9), 13% (7), and 11% (9) in AIH groups N, V, and K. Among in vitro studies with K added semen, an improvement of sperm motility was demonstrated in half of the specimens. In the capillary tube test (CTT), with wives' cervical mucus, a deterioration was more frequently seen than an improvement after 2 h, independent of the early effect of K in semen, K induced changes of CTT were less pronounced when donors' cervical mucus was used. The results of the in vitro studies offer an explanation for the low PR in the AIH program with K. PMID- 2327824 TI - Interaction between prostasomes and spermatozoa from human semen. AB - Prostasomes are prostate-derived organelles that occur freely in human seminal plasma. They promote forward motility of spermatozoa probably by closely interacting with them in an unknown manner. We have studied the interaction between human prostasomes and spermatozoa by applying them as two separate samples in free-zone electrophoresis. During the run these samples approached each other and finally fused into one single peak that was not further dissociated. Both the spermatozoa and prostasomes displayed a net-negative surface charge, the latter being less negative. This discrepancy in charge was even more pronounced by pretreatment of prostasomes with neuraminidase, which, however, did not affect the interaction. This implies a strong interaction of a probable hydrophobic character between cells and organelles. The presence of prostasomes and spermatozoa in the fused, single peak was confirmed by transmission electron microscopy. Evidence for interaction was apparent in transmission electron microscopy after embedding in a hydrophilic, but not in a hydrophobic, resin. This observation supports the view that the bonds between prostasomes and spermatozoa are of hydrophobic character. This type of interaction enables the prostasomes to act in close vicinity to spermatozoa and may create the prerequisites for a proper microenvironment of the spermatozoa favoring their forward motility. PMID- 2327825 TI - Effects of manganese and other divalent cations on progressive motility of human sperm. AB - Manganese (Mn2+) stimulated the progressive motility of human washed sperm in a time- and dose-dependent manner. This confirmed previous data indicating a capacity for activating the adenylyl cyclase of sperm homogenates in vitro. A maintained response was best seen with doses 0.2-1.0 mM. After an initial stimulation, higher concentrations of up to 20 mM were associated with a decline in the response to control levels. Magnesium ions (Mg2+) stimulated motility in the same dose range but to less than 50% of the Mn2+ response. Other divalent cations such as zinc (Zn2+), strontium (Sr2+), and Calcium (Ca2+) also exerted stimulatory effects to varying degrees in descending order. Metal ion effects on sperm motility may be mediated through a common cation-binding site on the adenylyl cyclase. PMID- 2327826 TI - Ultrastructure of paracriny/steroidogenesis in principal cells of the marmoset epididymis. AB - The ultrastructural features of the principal cell in the epididymal epithelium of the marmosets are distinguished by an intercellular exchange of substances contained within cytoplasmic vesicles and the presence of paracrystalline bodies. The possibility of the exchange of substances constituting paracriny and the paracrystalline inclusion having a role in steroidogenic activity is discussed. PMID- 2327827 TI - Ultrastructure of human bulbourethral glands and of their main excretory ducts. AB - The endpieces of human bulbourethral (BU) glands, studied with SEM after removal of the connective tissue, consist of short, coiled tubules often dilated into alveoli. Immunohistochemical studies at the EM level have shown that the mucous cells of these glands have mucous droplets, which react to blood group antigens, suggesting that BU glands participate in the secretion of these antigens into the seminal plasma. The main excretory duct is lined by a stratified columnar epithelium consisting of six-seven cellular layers. Cells of superficial layers, that are endowed with typical secretory granules, seem to contribute some unknown components to the secretions of these glands. PMID- 2327828 TI - Intracavernous papaverine in the management of psychogenic impotence. AB - Intracavernous papaverine has found an important place in the management of male erectile failure. The effect of this mode of therapy was studied in 48 patients with psychogenic impotence. The average follow-up for this group of patients ranged from 7 months to 37 months (mean 16.3 months). All the patients in this group were advised sex therapy as an initial mode of therapy. On refusal to undergo sex therapy, they were offered an option of intracavernous papaverine injection. Papaverine appears to break the performance anxiety erectile failure cycle and was noted to have good results. Overall 57.9% patients expressed complete satisfaction with this mode of therapy. One patient (2.1%) developed priapism, which was adequately treated with intracavernous epinephrine. Use of low dosage of papaverine is suggested as an additional mode of therapy in the management of psychogenic impotence. PMID- 2327829 TI - Blood/seminal serotonin levels in infertile men with varicocele. AB - Seminal and blood serotonin levels were measured in 37 men with varicocele and in 33 men without palpable varicocele. Elevated levels of blood serotonin and lower levels of seminal serotonin were found in oligozoospermic men with varicocele as compared with men having varicocele but normal seminal quality. No differences in seminal serotonin levels were observed in oligozoospermic men without varicocele. Elevated levels of blood serotonin and lower levels of seminal serotonin in semen in men with varicocele were associated with low sperm count, low sperm motility, low fructose levels, and high citric acid levels. It would appear that serotonin may play a role as an infertility determinant in subjects with varicocele. PMID- 2327830 TI - Prevention of high altitude-induced testicular disturbances by previous treatment with cyproheptadine in male rats. AB - Male rats were exposed to 4,340 m altitude for 4 days. At this time histological alteration in the testes were observed. There were tubules with pyknotic primary spermatocytes and spermatids, necrosis of numerous cells, and sloughing of primary spermatocytes. The damaged areas were limited by normal tissue. Serum testosterone increased significantly after 4 days of exposure. Administration of an anti-serotoninergic compound, cyproheptadine (10 mg/kg body weight), prevented the high altitude-induced changes in both spermatogenesis and serum testosterone. These observations suggest that serotonin is involved in the testicular changes that occurred when rats are acutely exposed to high altitude. PMID- 2327831 TI - Testicular steroids in spermatic and peripheral veins after single injection of hCG in patients with varicocele. AB - To determine the function of Leydig cells in patients with varicocele, hCG stimulated levels of progesterone (Prog), 17 alpha-Hydroxy-4-pregnene-3,20-dione (17OHP), 4-Androstene-3,17-dione (A-dione), testosterone (T), and estradiol-17 beta (E2) in both spermatic and peripheral veins were measured. Seventy-two patients with idiopathic varicocele were divided into four groups: patients in group 1 were untreated, whereas patients in groups 2, 3, and 4 were given a single i.m. injection of 10,000 IU hCG 24 h, 96 h, and 168 h before surgery, respectively. In the spermatic and peripheral veins, levels of Prog, 17OHP, and E2 showed peaks at 24 h, whereas levels of A-dione and T showed peaks at 96 h. Significant increases in the ratios of spermatic veins 17OHP to A-dione and 17OHP to T, and a significant decrease in the ratio of T to E2, was found 24 h following hCG treatment. These results demonstrate that, following hCG injection, there is a transient inhibition of testicular C17-20-lyase activity, probably mediated by E2, even in subfertile males with varicocele. PMID- 2327832 TI - Scrotal temperature and semen quality in men with and without varicocele. AB - The exact role of varicocele in human male infertility remains controversial. Fifty-five male partners of infertile couples randomly selected and 17 fertile semen donors were evaluated for semen quality, scrotal temperature, and presence of varicocele using clinical palpation and Doppler ultrasound. The incidence of varicocele was 42% in male partners of infertile couples and 41% in fertile semen donors. Left scrotal temperature was significantly (p less than .001) higher in infertile males with varicocele as compared to all groups. No significant differences were observed in the percentage of morphologically normal sperm in semen of males with and without varicocele. However, the incidence of tapered, elongated, and immature sperm was significantly higher in the infertile patient population with a varicocele. Measurement of scrotal temperature and assessment of sperm morphology may be used as predictors of the presence and deleterious effect of varicocele. PMID- 2327833 TI - Immunomagnetic method to select human sperm without sperm surface-bound autoantibodies in male autoimmune infertility. AB - Using supermagnetic polymer microspheres coated with anti-immunoglobulins, spermatozoa without autoantibodies bound on their surface can be isolated from a sperm population showing a variable percentage of cells with autoantibodies bound on their surface. This simple technique seems to induce no modification of semen qualities; therefore, the concentration of sperm after immunomagnetic separation might be useful for in vivo or in vitro insemination in infertile couples with autoimmune male infertility. PMID- 2327834 TI - Serologic tests for antibody to Borrelia burgdorferi. Another Pandora's Box for medicine? PMID- 2327835 TI - Methotrexate and liver biopsies. Is it really necessary? PMID- 2327836 TI - Iofetamine I 123 single photon emission computed tomography is accurate in the diagnosis of Alzheimer's disease. AB - To determine the diagnostic accuracy of iofetamine hydrochloride I 123 (IMP) with single photon emission computed tomography in Alzheimer's disease, we studied 58 patients with AD and 15 age-matched healthy control subjects. We used a qualitative method to assess regional IMP uptake in the entire brain and to rate image data sets as normal or abnormal without knowledge of subjects'clinical classification. The sensitivity and specificity of IMP with single photon emission computed tomography in AD were 88% and 87%, respectively. In 15 patients with mild cognitive deficits (Blessed Dementia Scale score, less than or equal to 10), sensitivity was 80%. With the use of a semiquantitative measure of regional cortical IMP uptake, the parietal lobes were the most functionally impaired in AD and the most strongly associated with the patients' Blessed Dementia Scale scores. These results indicated that IMP with single photon emission computed tomography may be a useful adjunct in the clinical diagnosis of AD in early, mild disease. PMID- 2327837 TI - Beneficial long-term effects of hydralazine in aortic regurgitation. AB - The long-term effects of vasodilators in asymptomatic patients with aortic regurgitation have not been studied extensively. We retrospectively reviewed the echocardiograms of 19 asymptomatic patients with significant aortic regurgitation followed up annually for up to 4 years (average +/- SD, 3.1 +/- 0.7 years). Of these 19 patients, 12 were not receiving vasodilators and 7 were receiving hydralazine hydrochloride, 40 to 200 mg daily. In the patients not receiving vasodilators, left ventricular diastolic and systolic dimensions increased progressively in all patients by an average of 8% and 13%, respectively, after 3 years. In the patients receiving hydralazine, left ventricular dimensions increased by 9% and 5% in the year or more before hydralazine use and decreased by 7% and 7%, respectively, during the first year after using hydralazine. The reduction was observed in all patients during the first year, but an increase was detected in 3 patients followed up beyond that period. The results suggest that the progression of left ventricular dilatation in asymptomatic patients with aortic regurgitation can be delayed by long-term therapy with vasodilators. Pending further confirmation, such therapy may possibly influence the natural history of the disease and delay the timing of operation. PMID- 2327838 TI - Trends in hospitalization rates for heart failure in the United States, 1973 1986. Evidence for increasing population prevalence. AB - Discharge data from a representative sample of short-stay US hospitals were examined to obtain information regarding trends in the prevalence of congestive heart failure from 1973 through 1986. During this 14-year period, the number of discharges more than doubled and the age-adjusted rates increased from 53% to 88% among the four major sex-race groups. On average, nonwhite men experienced annual hospitalization rates 33% higher than white men, while for women the corresponding nonwhite rates were 50% higher. Hospitalization rates during this period remained constant for persons younger than 55 years but rose sharply in the elderly. Concurrently, a slight decline in case fatality rates for an individual hospitalization was seen. The two factors accounting for the growing prevalence of congestive heart failure seem to be the increasing average age of the population and the longer survival of persons with chronic heart disease. The role of improved medical therapy during the period of this study remains uncertain. Increasing demands to provide care for the congestive heart failure syndrome are likely to continue in the coming years, and medical facilities should develop new intervention strategies to treat or prevent the underlying conditions leading to heart failure as well as decrease the need for hospitalization in this common disorder. PMID- 2327839 TI - Informed consent for colonoscopy. A prospective study. AB - Central to the nature of the physician-patient relationship is how fully patients are informed about their disease and prognosis and how active a role they take in deciding treatment; the "autonomy" and "paternalistic" models represent current poles of physician behavior. While informed consent has become ubiquitous in medical practice, it is not clear to what extent the value of patient autonomy has entered into everyday medical decisions. To evaluate informed consent, we prospectively surveyed 102 outpatients scheduled to undergo a colonoscopy and 16 of their physicians. The colonoscopy examination is straightforward and offers an optimal opportunity for patient participation in decision making. We found that most patients wanted guidance from their physicians and most physicians did not view the patient as autonomous. The more traditional parentalistic model continues to influence the physician-patient relationship, at least for this technical endeavor. PMID- 2327840 TI - Prediction of glucose response to weight loss in patients with non-insulin dependent diabetes mellitus. AB - Although diet therapy is considered the cornerstone of therapy for obese patients with non-insulin-dependent diabetes mellitus, losing weight is often difficult, and the plasma glucose concentration does not always improve after weight loss. We looked for predictors of improvement in plasma glucose levels after weight loss in 135 obese patients with non-insulin-dependent diabetes mellitus who had lost at least 9.1 kg of body weight. After weight loss there was a bimodal distribution of plasma glucose levels, allowing us to identify patients as "responders" or "nonresponders" according to whether a random plasma glucose level was above or below 10.0 mmol/L after a 9.1-kg weight loss. Fifty-five (41%) of 135 patients were responders (after a 9.1-kg weight loss, the mean +/- SEM plasma glucose level was 7.0 +/- 0.2 mmol/L). Many responders had improved plasma glucose levels after only slight weight loss. Eighty (59%) of 135 patients were nonresponders (after a 9.1-kg weight loss, the mean +/- SEM plasma glucose level was 18.3 +/- 0.6 mmol/L). Although the responder and nonresponder groups were comparable in age, sex distribution, plasma glucose levels, and body weight at initial presentation, improvement in the plasma glucose level after weight loss could be predicted by a plasma glucose level of 10.0 mmol/L or lower after 2.3-kg (62% positive predictive value) and 4.5-kg (79% positive predictive value) weight loss. We conclude that, in contrast to conventional teaching, many patients with non-insulin-dependent diabetes mellitus will not have any improvement in plasma glucose levels after a 9.1-kg weight loss. However, a substantial minority (approximately 40%) of obese patients with non-insulin-dependent diabetes mellitus have much lower plasma glucose levels with a weight loss of 9.1 kg or less. Although the plasma glucose response to weight loss cannot be forecast by initial clinical parameters, the success or failure of diet therapy can be predicted from the plasma glucose level after a weight loss of only 2.3 to 4.5 kg. Mild or moderately obese patients with non-insulin-dependent diabetes mellitus who remain hyperglycemic after a weight loss of 2.3 to 9.1 kg are unlikely to improve with further weight loss and should be considered for treatment with insulin or oral hypoglycemic agents. PMID- 2327841 TI - Cystometric evaluation of bladder dysfunction in elderly diabetic patients. AB - To select the appropriate treatment for an elderly patient with urinary incontinence, the cause of the incontinence needs to be determined. In diabetic patients who are incontinent, the underlying problem has been described in the past as urinary retention secondary to autonomic neuropathy. In cystometric studies conducted on 23 elderly diabetic nursing home patients (mean age, 80 years; 19 women, 4 men), who presented with symptoms of urinary dysfunction, involuntary contractions were demonstrated in 61% of the subjects. Thirteen percent of the patients had normal voluntary contractions of the bladder, 17% had voluntary contractions of a low magnitude, and 9% had no contractions at all. The majority (76%) of the subjects presenting with urinary incontinence had involuntary bladder contractions, while all of the subjects presenting with urinary retention had either voluntary contractions of a low magnitude or no contractions. It cannot be assumed that all elderly diabetic patients presenting with urinary symptoms have poorly contracting bladders (diabetic bladder). Urodynamic studies can be helpful when choosing therapy for the elderly diabetic patient with urinary dysfunction. PMID- 2327842 TI - Clinical and microbiological evidence for endemic pharyngitis among adults due to group C streptococci. AB - Group C beta-hemolytic streptococci cause rare epidemic outbreaks of pharyngitis, but their role in sporadic endemic pharyngitis has been uncertain. We addressed the question of whether non-group A beta-hemolytic streptococci are associated with endemic pharyngitis in two ways. First, we compared rates of isolation from throat swabs of group A, B, C, and G and ungrouped beta-hemolytic streptococci ("culture negative") in adult patients vs those rates in controls. Second, we collected in standardized form clinical indexes of patients with pharyngitis: signs and symptoms graded for severity, the examining physician's subjective estimate of the probability of streptococcal pharyngitis, a logistic regression score predicting streptococcal pharyngitis, and whether antibiotic therapy was prescribed. After collecting data and cultures on 1425 patients with sore throats and cultures on 284 controls, we found the following: group C streptococci were isolated significantly more frequently in patients with sore throats than in controls (6% vs 1.4%); four clinical signs and two symptoms distinguished group C associated pharyngitis as more severe than culture-negative pharyngitis; and six clinical signs and one symptom distinguished group C-associated pharyngitis as less severe than group A pharyngitis. Physicians' subjective estimates, logistic regression scores, and antibiotic treatment all characterized group C-associated pharyngitis as more severe than culture-negative sore throats but less severe than group A pharyngitis. From these data we present the first definitive evidence that group C streptococci are associated with endemic pharyngitis, show that clinical presentation distinguishes a group of patients with group C associated pharyngitis from populations with culture-negative sore throats and from those with group A pharyngitis. Physicians' response to that presentation merits consideration in the context of rapid group-specific diagnosis of streptococcal pharyngitis by group A antigen tests. PMID- 2327843 TI - The cost of acquired immunodeficiency syndrome in northern California. The experience of a large prepaid health plan. AB - We studied the cost of acquired immunodeficiency syndrome (AIDS) in the Kaiser Permanente Medical Care Program (KPMCP), northern California region. We report the costs of care to the KPMCP and introduce an innovative application of survival methods to cost analysis. From the beginning of the AIDS epidemic in 1981 to the end of June 1987, 866 cases of AIDS were recorded among members of the KPMCP. Estimates of the costs of care of these patients were derived from comprehensive chart reviews of a random sample of 71 patients whose conditions were diagnosed from January 1984 through June 1987. Total mean lifetime costs per patient were $32,816 (median, $28,677), whereas the mean hospital per diem cost was $20,446 per patient. As more care was shifted to outpatient services overtime, overall costs dropped, despite marked increases in the cost of outpatient medications such as zidovudine. The overall estimate of cost compared closely with other estimates of the cost of care in San Francisco, Calif, and it is lower than estimates from elsewhere in the United States, probably because of the low proportion of cases associated with intravenous drug use and the well developed social support networks available to patients with AIDS in the San Francisco Bay Area. PMID- 2327844 TI - The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly. AB - We interviewed 315 consecutive elderly patients admitted to an acute care hospital to determine the percentage of elderly hospital admissions due to noncompliance with medication regimens or adverse drug reactions, their causes, consequences, and predictors. Eighty-nine of the elderly admissions (28.2%) were drug related, 36 due to noncompliance (11.4%), and 53 due to adverse drug reactions (16.8%). One hundred three patients had a history of noncompliance (32.7%). Factors statistically associated with a higher risk of hospitalization due to noncompliance were poor recall of medication regimen, seeing numerous physicians, female, medium income category, use of numerous medications, and having the opinion that medications are expensive. Factors associated with an increased risk of an admission due to an adverse drug reaction were use of numerous different medications, higher medication costs, receiving Medicaid, and not receiving any home services. In conclusion, many elderly admissions are drug related; noncompliance accounting for a substantial fraction of these. Elders at high risk of being noncompliant are identifiable using a variety of criteria. Economic factors were important in predicting admissions due to noncompliance as well as adverse drug reactions. PMID- 2327845 TI - Clinical manifestations of systemic lupus erythematosus. Identification of racial and socioeconomic influences. AB - The identification of differences in the clinical manifestations of systemic lupus erythematosus (SLE) due to racial and socioeconomic factors has been hampered in previous studies by limitations in the numbers of black patients examined. We sought to define racial differences in the cumulative clinical manifestations of SLE in a large, racially balanced cohort (184 black patients and 174 white patients). Differences in the cumulative disease manifestations of SLE between black and white patients were evaluated by multivariate regression techniques, controlling for socioeconomic status and the potential confounding factors of age, gender, duration of follow-up, and treatments. Race was found to be an important factor influencing the prevalence of 9 of 24 clinical features of SLE. As a group, blacks more commonly manifested anti-Sm and anti-RNP antibodies, discoid skin lesions, and proteinuria, and less commonly manifested photosensitivity, than whites. Among specific age, gender, and socioeconomic subgroups, blacks were more likely than whites to have had psychosis, serositis, and urinary cellular casts, and less likely to have had sicca syndrome. Racial differences in the prevalence of renal failure were due to socioeconomic effects. These results suggest that race is under-recognized as a factor influencing the clinical heterogeneity of SLE. PMID- 2327846 TI - Prevalence of undiagnosed eye disease in high-risk diabetic individuals. AB - A total of 533 diabetic individuals using the Marshall, Minn, medical care system were identified as potential subjects for a study of unrecognized eye disease. Of these, 172 (32%) stated they had never had an ophthalmologic eye examination and subsequently were defined as being at high risk for unrecognized diabetic eye disease. Ophthalmic examination was performed on 145 (84%) of these high-risk individuals and revealed that 61% had clinical characteristics consistent with diabetic retinopathy, glaucoma, cataract, or other eye abnormalities. Twenty-five (17%) of these subjects presented with eye disease that required immediate treatment, referral, or accelerated follow-up. Of those indicating they had an ophthalmologist, approximately 35% reported a time since last visit of 2 years or greater. These findings indicate a high prevalence of ocular morbidity among diabetic individuals who are not under routine ophthalmic surveillance and suggest that improvements in patient and professional compliance with recommended guidelines for eye care are warranted. PMID- 2327847 TI - Cocaine and marijuana use by medical students before and during medical school. AB - A survey of alcohol and other drug-use patterns of 300 second- and third-year students at a mid-Atlantic private medical school was undertaken in 1987. Two hundred sixty-three (88%) of the medical students surveyed completed the anonymous questionnaire. Tobacco use decreased from 11% before to 4% during medical school. Before entry into medical school, 21% of the respondents had smoked marijuana 10 times or more, usually at least monthly, while 9% had smoked marijuana 10 times or more during medical school. Six percent had smoked marijuana daily in high school or college, while 1% smoked marijuana daily in medical school. Few students who used cocaine before medical school abstained from it during medical school. Cocaine was used by 17% of the respondents before and during medical school. Frequent use of cocaine (greater than 10 times) during medical school, reported by 5% of the students, was directly related to excessive alcohol intake, tobacco dependence, frequent use of marijuana before and during medical school, and medical and behavioral problems related to alcohol and other drug use. Less than 25% of medical schools have a formal policy aimed at identifying impaired students, and only 12% have formal treatment protocols for helping impaired students. We propose that all medical schools initiate programs to diagnose alcohol and other drug-abuse problems in medical student candidates and in the students themselves, and that intervention for any alcohol or other drug problem be encouraged and supported by formal medical school policies designed to help the impaired student. PMID- 2327849 TI - Multiple rheumatoid nodules of the renal cortex. AB - We report the findings of a large localized collection of rheumatoid nodules in the renal cortex of a male patient with long-standing seropositive rheumatoid arthritis. Rheumatoid nodules are a rare occurrence in the urinary tract, with only two previous reports of renal involvement, to our knowledge. A possible relationship, on the basis of immunologically mediated mechanisms, to accompanying chronic pyelonephritis is proposed. PMID- 2327848 TI - Methotrexate-induced cirrhosis requiring liver transplantation in three patients with psoriasis. A word of caution in light of the expanding use of this 'steroid sparing' agent. AB - Methotrexate has been used for many years to treat refractory psoriasis. Three cases of methotrexate-induced cirrhosis requiring orthotopic liver transplantation are presented to emphasize the importance of strict adherence to published criteria for patient selection, monitoring of cumulative drug dosages, and the performance of serial liver biopsies. Each patient had been treated with long-term methotrexate therapy (cumulative doses far in excess of 1.5 g) without undergoing serial liver biopsies, contrary to well-established treatment guidelines. Caution must be exercised in using methotrexate as a steroid-sparing agent in the treatment of inflammatory diseases because of its potential to cause severe hepatotoxic effects with long-term usage and cumulative doses above 1.5 g. Patients easily become psychologically dependent on the drug, and physicians need to guard against the false sense of security engendered by normal results on liver function studies. PMID- 2327850 TI - Cobalamin deficiency and red blood cell volume distribution width. PMID- 2327852 TI - Mental dysfunction and cobalamin deficiency. PMID- 2327851 TI - Low serum cobalamin levels in pernicious anaemia. PMID- 2327853 TI - Asymptomatic hematuria in women. PMID- 2327854 TI - Cardiopulmonary resuscitation. PMID- 2327855 TI - Malaria prophylaxis in high-risk travelers. PMID- 2327856 TI - Control of hypertension and reversal of renal failure in undifferentiated connective tissue disease by enalapril. PMID- 2327857 TI - Variability of serum phenytoin concentrations in nursing home patients. PMID- 2327858 TI - Occupational exposure to organic solvents. PMID- 2327859 TI - Prediction of in-hospital cardiopulmonary arrest outcome. PMID- 2327860 TI - Verapamil vs quinine in recumbent nocturnal leg cramps in the elderly. PMID- 2327861 TI - Statistical medicine. PMID- 2327862 TI - Effect of pentoxifylline on carbohydrate metabolism in type II diabetics. PMID- 2327863 TI - [Sublethal microcephalic chondrodysplasia. Taybi-Linder syndrome, primordial microcephalic nanism types I and III]. AB - The authors describe a case of microcephalic dwarfism observed in a newborn until 10 months of age and discuss the diagnostic challenge. They show that the Taybi Linder syndrome and the primordial dwarfism type I and type III of Majewski are an identical recessive autosomal entity. The radiological evolution explains the initial separation of type I and type III. Because of the skeletal lesions, lacking in the Seckel syndrome, the name of sublethal microcephalic chondrodysplasia is proposed for this disease. PMID- 2327864 TI - [Incomplete androgen insensitivity syndrome. Difficulties of diagnosis and management]. AB - A familial form of incomplete androgen insensitivity syndrome (AIS) is reported. The index case was first seen at 9 months of age for ambiguous genitalia. Diagnosis of AIS, suspected but first discarded on the basis of an androgen sensitivity test, was finally made at puberty on the discordance between poor virilization and elevated levels of both testosterone and LH, a florid gynecomastia, and the exclusion of any enzymatic defect in testosterone biosynthesis of 5 alpha-reductase deficiency. Androgen receptors in public skin were within the limits of normal for total number, with normal affinity. Familial occurrence included 2 first cousins born 7 and 10 years later, a maternal grand uncle with similar ambiguous genitalia, and a maternal uncle with the gynecomastia-preserved fertility syndrome. This case report illustrates the heterogeneity of AIS in a given family and the difficulty of and early positive diagnosis in a newborn presenting with sexual ambiguity. PMID- 2327865 TI - [Dysphagia, speech disorders and centrotemporal spikes-waves]. AB - Repeated paroxysmal oropharyngeal fits consisting of sialorrhea and speech arrest are described in a 5 year-4-month old patient. Investigations were initially oriented towards a laryngeal or a gastrointestinal disease. Electroencephalographic tracings showed repeated bilateral centrotemporal spikes waves discharges which sometimes were associated with bilateral facial clonic contractions synchronous with anarthria and sialorrhea. Consciousness was preserved. Attacks were related with a cluster of fits of a partial epilepsy. Transient pseudo-bulbar palsy (anterior opercular syndrome) resulted from seizures: loss of identifiable speech, drooling with difficulties in swallowing, absence of palatal movements and of the gag reflex. Intellectual functions remained normal. Other investigations were all normal (CT scan, MRI, cytologic and immunological CSF studies). With common anticonvulsant drugs (Valproate and Carbamazepine) seizures resolved within a few weeks. These findings suggest that this particular epilepsy is an unusual type of benign partial epilepsy with centrotemporal (or Rolandic) spikes. PMID- 2327866 TI - [Rheumatoid purpura and acute post-infectious glomerulonephritis]. AB - The authors report the case of a 33 month-old child who presented some of the classical symptoms of the Henoch-Schoenlein purpura - arthritis, purpuric lesions of the lower extremities - associated with the full-blown picture of a post infectious glomerulonephritis - low level of C3, proliferation of mesangial cells, exudation with large number of leukocytes, and C3 glomerular deposits. These findings and others previously described suggest that the Henoch-Schoenlein purpura is a syndrome and that some of its manifestations may occur in patients with post-infectious glomerulonephritis. PMID- 2327867 TI - [Hereditary epidermolysis bullosa and laryngeal involvement]. AB - Two cases of epidermolysis bullosa (EB) with laryngeal involvement are reported in 2 Algerian girls, aged 6 and 7 years. The first one with a junctional EB, received local treatment with good results. For the second, with an EB dystrophica, tracheostomy was necessary and remained so. Laryngeal involvement is rare in EB. It and remained so can be serious and life-threatening. Eight cases where previously reported. Their clinical and therapeutical particularities are discussed. PMID- 2327868 TI - [Allergy to latex gloves. A cause of surgical shock]. AB - Latex induced anaphylaxis was observed in 2 children during surgical procedures. Anaphylaxis was due to exposure to surgical latex gloves. The diagnosis should be suspected in patients with a previous history of rubber induced urticaria and is confirmed by positive skin tests to latex. In patients presenting with allergy to latex, prophylaxis is based on the use or surgical gloves made of vinyl or neoprene. PMID- 2327869 TI - [Nature, frequency and variability of health counseling by 7 pediatric physicians ]. AB - A prospective study of health counseling was conducted in 7 private pediatric ambulatory settings. The frequency, duration, differences and contents of these advices are given. These latter were classified as systematic (given by the pediatrician), given (occasional), requested, preventive, or therapeutic, for statistical analysis. 1,703 counsels were registered during 1,503 consultations. 828 of them health counsels (HC) and will be reported here. Educational HC were the most frequent, followed by those concerning therapy, hygiene, immunization and nutrition. The mean counsel duration was 2 minutes. Their frequency and contents varied greatly among the 7 pediatricians. The content of the immunization counsels only was homogeneous. 22% of the HC were systematic, when 47% were requested. A better teaching of health counseling would further improve the credibility and efficacy of health counseling in pediatric practice. PMID- 2327870 TI - [Apropos of the treatment of angina in children with tiaprofenic acid]. PMID- 2327871 TI - [Sclerosing cholangitis in the course of histiocytosis X]. PMID- 2327872 TI - [Purulent pericarditis with meningococcus]. PMID- 2327873 TI - [Heart transplantation in children. Problems and perspectives]. PMID- 2327874 TI - [Pure genetic thrombocytopenia. A new clinical entity]. AB - From a retrospective study of 3,500 platelet kinetic studies, we isolated 51 cases with chronic thrombocytopenia, excessive platelet volume without Dohle bodies and no functional platelet anomalies, normal megakaryocyte count and normal autologous and homologous platelet life-span. These cases were either discovered during the first year of life (i.e. constitutional) or proved as familial (with autosomal dominant transmission). Previous therapies (corticosteroids, immune globulins, androgens, immuno-suppressive agents, splenectomy) were unefficient in all cases as in their relatives. PMID- 2327875 TI - [Neonatal Pepper's syndrome. Apropos of a series of 22 cases]. AB - From 1960 to 1987, 22 neonates were treated at the Institut Gustave-Roussy for a Pepper' syndrome. During this period of time, 83 children were treated for the same syndrome, the neonatal type representing 26% of cases. Twelve of the 22 neonates presented with the rapidly evolving type, requiring an immediate aggressive treatment. In 4 of them death occurred early despite treatment. The 10 other neonates presented with a slowly progressive disease. In 5 of them treatment of the metastatic disease was not necessary to obtain remission. The survival rate of disease without relapses in 77%, with a median follow-up of 8 years. So, despite the high incidence of rapidly progressive forms, the prognosis of this disease remains favorable in neonates, provided an accurate treatment initiated early. PMID- 2327876 TI - Fostering the interdisciplinary team, fostering research in a society in transition. PMID- 2327877 TI - Types of affective response to stroke. AB - Most studies of depression after stroke have included heterogeneous samples of patients. These studies have generally not qualified patients as to age, absence of neurologic, psychiatric, and substance abuse histories, and other complicating factors. Of 155 inpatient rehabilitation admissions after acute unilateral cerebrovascular accident, only 26 met the following strict criteria for inclusion: age older than 55 years, no history of or concomitant brain disease or injury, and no history of major affective, thought, or substance abuse disorder. Two examiners independently administered the Hamilton Depression Rating Scale, a mood adjective checklist, and a modified Mini-Mental State Examination to 20 subjects who agreed to participate. They also rated subjects on research diagnostic criteria for depression and obtained a dexamethasone suppression test for each subject. Eighteen subjects completed neuropsychologic evaluation. All evaluations were completed within six weeks of the patient's stroke. Subjects fell into four distinct clinical groups based on averaged data: (1) no affective symptoms, (2) verbal distress only, (3) vegetative symptoms only, and (4) a combined disorder with both distress and vegetative symptoms. The presence of verbal reports of distress, vegetative signs, or both were associated with longer hospital stays and greater neuropsychologic impairment. PMID- 2327878 TI - Return to work after stroke: development of a predictive model. AB - Seventy-nine stroke patients who underwent a vocationally oriented, comprehensive, inpatient stroke rehabilitation program were followed up to evaluate their return to work. At follow-up, 49% had returned to work a mean of 3.1 months after rehabilitation discharge. Factors associated with success and with failure of vocational rehabilitation were then identified, and a predictive model was developed. There were positive associations between return to work and Barthel Index on admission (p = 0.0002) and discharge (p = 0.0015). Negative associations were found between return to work and aphasia (p = 0.0009), rehabilitation length of stay (p less than 0.0001), and prior alcohol consumption (p = 0.03). A step-wise multiple regression model explained 42% of the variance in return to work. Those most likely to return to work were not aphasic; they had shorter rehabilitation lengths of stay and higher Barthel Index scores on discharge; and they were lighter consumers of alcoholic beverages before their strokes. In conclusion, a set of factors predictive of return to work in younger stroke patients was identified, including, most notably, a strong negative association with aphasia and an intriguing negative association with prior alcohol consumption. PMID- 2327879 TI - The ghost joint: transient osteoporosis of the hip. AB - Seven adult patients identified as having idiopathic transient osteoporosis of the hip (TOH) are reported. TOH is an uncommon entity, most often seen in women during the third trimester of pregnancy and in middle-aged men. It is characterized by groin pain, limited hip range of motion, nonspecific laboratory findings, localized radiographic evidence of osteopenia, and spontaneous recovery usually within two to nine months. Diagnosis remains dependent on clinical recognition and x-ray confirmation. Radioisotope scanning aids in the diagnosis; both bone and synovial biopsies are often less productive. Treatment consists of joint protection with limited weight bearing, range of motion exercise, progressive ambulation, and analgesics. An awareness of TOH facilities appropriate diagnosis and treatment and curtails unnecessary diagnostic procedures. PMID- 2327880 TI - Aided gait in rheumatoid arthritis following knee arthroplasty. AB - A study is presented of a biomechanical comparison of two different aided gait patterns used by rheumatoid arthritis patients after knee joint surgery. Subjects using alternating and step-to gait patterns were compared when ambulating with forearm-support crutches. Data were collected via instrumented walking aids and 16mm cameras. Values were derived for load transmission through the crutches and for moments at the elbow and shoulder joints. The alternate gait was, on average, 87% faster than the step-to gait, and imposed average loads less than 80% of that in the step-to gait. Peak upper limb joint moments attained values approaching 12Nm at the shoulder joint in both gaits. Given the vulnerability of the upper limb joints in these patients, the load transmission through the upper limb may be unacceptably high in both aided gait patterns. PMID- 2327881 TI - Kinematics of high-heeled gait. AB - High-heeled shoes cause postural changes, a loss in foot function, and increased shock loadings during gait, which must be compensated by accommodations in the kinematics of body segments proximal to the feet. The hypothesis tested in this study was that there are differences in the three-dimensional kinematics of the tibia, knee, hip, pelvis, trunk, and upper trunk between low-heeled and high heeled gait. Gait analysis of 14 subjects showed that during high-heeled gait subjects walked more slowly (p less than .001), had shorter stride lengths (p less than .001), and had higher stance time percentages (p less than .05). Kinematically, high-heeled gait compared to low-heeled gait, was characterized by significantly increased knee flexion at heelstrike (5.4 degrees vs 2.1 degrees, p less than .05) and during stance phase (22.6 degrees vs 19.2 degrees, p less than .05). During swing phase, high-heeled gait, compared to low-heeled gait, resulted in significantly lower knee flexion (66.1 degrees vs 72.1 degrees, p less than .05) and hip flexion (33.5 degrees vs 34.8 degrees, p less than .05). The range of motion of the pelvis in the sagittal plane was slightly lower in high-heeled gait than in low-heeled gait (7.0 degrees vs 7.9 degrees, p less than .05). No significant differences between low-heeled and high-heeled gait were found in the motions of the pelvis and trunk in the frontal and transverse planes. Statistical tests of intrasubject variability of angles of gait showed that five repeated trials were adequate for analysis of the tibia and knee in all planes of motion and for the hip in frontal and transverse planes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2327882 TI - Effect of serial casting for the prevention of equinus in patients with acute head injury. AB - Ten adults with traumatic head injury received serial casts within 14 days of injury for the prevention or correction of equinus. Eighteen limbs (16 bilateral) with spasticity were involved. An average of five casts for a total duration of four to 64 days were used for each limb. Comparisons of passive dorsiflexion measures before and after casting showed a mean gain of 21 degrees (paired t test, P less than .05). Of the 18 limbs, 13 reached a passive dorsiflexion of 0 degrees or more (ie, no equinus) which could be maintained without force for at least one hour. The procedures appeared safe and the results of the trial were clinically judged to be favorable. There is a need to further assess the efficacy of serial casting through randomized controlled trials and long-term followups. PMID- 2327883 TI - Oxygen consumption and cardiac response of short-leg and long-leg prosthetic ambulation in a patient with bilateral above-knee amputation: comparisons with able-bodied men. AB - This study measured oxygen uptake (VO2), minute ventilation (VE), and heart rate (HR) in a bilateral above-knee (AK) amputee and in three able-bodied controls during progressive treadmill exercise. Walking conditions for the amputee included using bilateral short-leg (SL) and long-leg (LL) prostheses. A progressive treadmill protocol to maximal capacity was used for the amputee and duplicated by the control subjects. An automated system was used to measure VO2, VE, and HR throughout exercise. Data analysis was restricted to the use of parameter averages and percentages to describe differences between experimental conditions. Maximal VO2 for the amputee averaged 23.3mL/kg-1/min-1 with the LL and 22.8mL/kg-1/min-1 with the SL prostheses, a negligible difference between conditions; however, exercise duration was 27% longer when using the SL prostheses. In addition, when averaged over the first four stages of exercise, VO2, VE, and HR were 24%, 32%, and 14% higher, respectively, when the LL prostheses were used. Treadmill walking by unimpaired controls averaged 47% and 79% more economical than walking with the SL or LL prostheses, respectively. These results demonstrate that the use of currently available AK prostheses requires significant energy expenditure, which limits their use to only the most physically fit individuals. PMID- 2327884 TI - Cardiorespiratory responses of mentally retarded adults to air-brake ergometry and treadmill exercise. AB - The graded treadmill (TM) exercise test is considered the optimal mode of exercise for evaluating the cardiovascular fitness of mentally retarded (MR) individuals. A new mode of exercise, the Schwinn Air-Dyne ergometer (SAE), was evaluated and compared to the TM for determining the cardiovascular fitness of adults. Twelve MR adults performed maximal exercise tests to volitional exhaustion, on separate days, on the SAE and TM. Maximal heart rates, oxygen consumption, minute ventilation, and respiratory quotient were similar for both exercise tests. These results indicate that the SAE is comparable to TM exercise in assessing the cardiovascular capacity of MR adults. PMID- 2327885 TI - Hospital supervised vs home exercise in cardiac rehabilitation: effects on aerobic fitness, anxiety, and depression. AB - This study focused on the effects of hospital supervision and type of prescribed home exercise in cardiac rehabilitation programs on aerobic fitness, anxiety, and depression. Men who had a myocardial infarction were randomly assigned to four exercise programs: The first program consisted of purely hospital-based exercise. The second and third programs combined hospital and home exercise, including either bicycling or walking at home. In the fourth program, patients were encouraged to exercise at home, but were given no specific guidance. Fifty-two patients finished the eight-week exercise program and 35 completed the psychologic questionnaires. At the end of the eight weeks, there were significant differences in the programs' effects on aerobic fitness. Purely hospital supervised exercise and the combination of hospital-supervised bicycling with home walking increased aerobic fitness more than completely unsupervised exercise. Furthermore, there were differences in the programs' effects on manifest anxiety. The combination of home and hospital bicycling was less beneficial than home walking and hospital bicycling or even completely unsupervised exercise at home. The results indicate that the degree of hospital supervision and the type of prescribed home exercise are important design features which may affect the success of cardiac rehabilitation exercise programs. No effects of the different exercise programs on patients' depression could be found. In general, a close relationship between aerobic fitness and anxiety or depression could not be demonstrated. Implications of these findings for the design of cardiac rehabilitation exercise programs are discussed. PMID- 2327886 TI - Cognitive dysfunction in spinal cord injury patients: sensitivity of the Functional Independence Measure subscales vs neuropsychologic assessment. AB - The Functional Independence Measure (FIM) has been developed to provide an objective measure of functional gains during acute and chronic rehabilitation of disabled individuals, including those with spinal cord injury (SCI). A unique characteristic of the FIM, as compared with other functional scales, is that it reflects abilities in the areas of communication and social cognition. In order to examine the external validity of these subscales, 41 acute SCI patients were evaluated with the FIM just before discharge from acute rehabilitation. The subscale scores were compared to the results of a comprehensive, predominantly motor-free, neuropsychologic battery administered 74.8 +/- 5.3 days postinjury. Evaluation of scatter plots indicated that there were no relationships between any neuropsychologic test results and the discharge FIM social cognition or communication subscale scores. This was attributed to a ceiling effect in the FIM ratings. The results of this study suggest that the FIM cannot be a substitute for comprehensive neuropsychologic assessment in SCI patients. PMID- 2327887 TI - Correlation of knee extensor muscle torque and spasticity with gait speed in patients with stroke. AB - The purpose of this investigation was to determine in 17 stroke patients the correlation between two independent variables (knee extensor muscle torque [KET] and spasticity on the paretic side) and one dependent variable (gait speed). The patients had a mean age of 59 years; time since onset of first stroke was 51 days. Each variable was measured twice on each of two consecutive days. Both KET and spasticity were measured on a Cybex II dynamometer. Peak torque was measured during five-second maximal voluntary isometric knee extension efforts. Spasticity was defined by the relative angle of reversal (RAR) of the Cybex electrogoniometer curve obtained during pendulum tests. Gait speed was measured as patients walked 8.0 meters at their most comfortable speed while using their usual devices. The average of each day's KETs, RARs, and gait speeds was used in the calculation of Pearson product moment correlations. The correlations between KET and gait speed were significant (p less than .05) and were .574 (day 1) and .571 (day 2). The correlations between the RAR and gait speed were not significant (-.204 day 1 and -.262 day 2). All measurements had intraday and/or interday reliability coefficients (ICC 3,1) exceeding .930. The results of this study confirm that gait performance is correlated with measures of KET but not spasticity in stroke patients. Thus, at the knee, extensor muscle torque, unlike spasticity, appears to be justified as a practical and objective clinical measure. PMID- 2327888 TI - Peak torque values for antagonist muscle groups and concentric and eccentric contraction types for elite sprinters. AB - The purpose of this study was to provide descriptive strength estimates of the major muscle groups of the lower limbs for a group of elite sprinters by comparing both the eccentric and concentric and the agonist and antagonist peak torques. The peak torque values of the flexor and extensor muscle groups of the hip, knee, and ankle joints of the lower extremities were tested in a group of elite male and female sprinters. These values were measured both eccentrically and concentrically for each of the joint movements tested, using a Kin/Com isokinetic dynamometer. The peak torque values for the knee joint were found to be substantially larger than those reported for nonathletes, and comparable to those for other athletic populations. No comparable scores were located for the results of the hip and ankle scores. The flexion and extension ratios for the knee joint, at approximately .60, were similar to others reported, whereas the ratios for the hip joint were larger at .76. The concentric and eccentric ratios varied, depending on the speed of testing and the joint tested. PMID- 2327889 TI - A functional electric stimulation system using an electrode garment. AB - A functional electric stimulation system for standing and ambulating that uses a commercially available electrode garment has been developed. The garment allows electrodes to be applied rapidly and securely. Two channels of a four-channel stimulator are used to stimulate the quadriceps muscles and permit the user to stand. The other two channels are used to stimulate the peroneal nerve, which causes a flexor withdrawal reflex and permits stepping. The user controls stepping by hand-held switches. The system provides a means for standing, exercising, and limited ambulation. PMID- 2327890 TI - Cervical spine rotation and lateral flexion combined motion in the examination of the thoracic outlet. AB - The axial rotation and simultaneous lateral flexion of the cervical spine is kinesiologically related to the movements of the upper thoracic spine. Five brachialgia patients were found to have a hypomobile first rib on the painful side in a cineradiographic study. The kinesiologic finding was the following: when the neutrally positioned cervical spine was first maximally rotated passively away from the painful side, the passive lateral flexion was restricted in this position. This can be due to the first thoracic transverse process bumping against the subluxated first rib. This test of cervicothoracic mobility is useful in the examination of the thoracic outlet function. PMID- 2327891 TI - Focal dystonia following soft tissue injury: three case reports with long-term outcome. AB - Three cases of focal dystonia are described which followed upper extremity injuries. Each patient developed a dystonic posturing in that limb; two patients improved when their initial condition was addressed. Various authors have proposed that focal dystonia represents a limited form of generalized dystonia, which is believed to result from a disturbance of striatopallidal-thalamic input to the supplementary motor area (SMA)--a vital executive area for motor control. An alternative hypothesis is offered; that is, a similar dysfunction of the SMA could be the result of altered sensory information from a painful limb disturbing the crucial integration between sensory input and motor performance. The following three examples of such integration are provided: (1) the long loop or transcortical reflex, (2) input of distinctive somatosensory neurons to the SMA, and (3) the projection of proprioceptive and tactile sensory input into peripheral receptive fields of the motor cortex. PMID- 2327892 TI - Sexual dysfunction in male and female patients with epilepsy: a study of 86 outpatients. AB - Sexual dysfunction is a well-known complication of chronic somatic illness. Eighty-six consecutive epileptic outpatients, 38 men and 48 women, without accompanying disorders, were studied. The frequency and symptoms of sexual dysfunction were compared with results from previous studies using identical sexological methodology. The previous studies were of diabetic patients and healthy controls. Eight percent of the epileptic men reported a sexual dysfunction compared to 44% of the diabetics and 13% of the controls. Epileptic women, diabetic women, and controls showed no significant differences in sexual dysfunction (29%, 28%, and 25%, respectively). In both sexes, the sexual function measured by frequencies of coitus and masturbation was normal. Most patients had good control of epileptic attacks on a treatment of monotherapy. Hormonal status was generally within normal limits in both men and women; only a few minor differences were found and they showed no correlation with sexual dysfunction. Psychologically and socially the patients did not differ appreciably from normals, and they exhibited a high degree of disease acceptance. This study, using a biopsychosocial approach in understanding sexual dysfunctions, is in contrast with previous, mainly uncontrolled, studies of epileptic patients that reported high frequencies of "hyposexuality" in males. We conclude that epilepsy does not necessarily increase the risk of sexual dysfunction in male or female. PMID- 2327893 TI - Psychophysiological assessment of male sexual arousal following spinal cord injury. AB - Adult males with and without permanent damage to the spinal cord were contrasted in terms of their sexual responsiveness to erotic stimulation in film, spoken text, and fantasy modes. Among the 16 spinal cord injured (SCI) men who were studied, several who had anticipated they would achieve erection failed to do so, whereas others demonstrated penile tumescence during erotic stimulation despite claiming they had lost the capacity for psychogenic erection. Self-report is thus not a valid index of sexual responsivity following spinal cord injury. Levels of tumescence varied across modalities of stimulation in the same manner for SCI and non-SCI men, and within each modality the two groups demonstrated similar rates of buildup of arousal over segments of stimulation. The SCI men without erections should not be considered asexual since their subjective arousal paralleled the subjective arousal of the non-SCI men and the SCI men with erections. PMID- 2327894 TI - Female ejaculation: perceived origins, the Grafenberg spot/area, and sexual responsiveness. AB - Despite earlier contrary claims, some researchers have recently reported a possible homologous female prostate gland that is potentially involved in a sudden spurt of fluid being released at the moment of orgasm. A number of medical authorities have speculated that this fluid is urine. To alleviate concerns about the possible release of urine during orgasmic response as well as to contribute to a further understanding of physiological and psychological sexual satisfaction, we examined a series of variables thought to be associated with female ejaculation [(expulsion of fluid during orgasm and its relationship, if any, to a sensitive anatomic area (Grafenberg spot)]. An anonymous questionnaire was distributed to 2350 professional women in the United States and Canada with a subsequent 55% return rate. Of these respondents, 40% reported having a fluid release (ejaculation) at the moment of orgasm. Further, 82% of the women who reported the sensitive area (Grafenberg spot) also reported ejaculation with their orgasms. A number of variables were associated with this perceived existence of female ejaculation. PMID- 2327895 TI - Guilt reactions to sexual fantasies during intercourse. AB - This study explored how guilt feelings about having sexual fantasies during intercourse are related to frequency of fantasizing, to sexual satisfaction and sexual dysfunction, and to different beliefs about the cause, transgressive nature, and consequences of such fantasizing behavior. Drawing from a sample of 178 men and women with intercourse experience (means age = 27), 84% reported that they fantasized at least some of the time during sexual intercourse. From this sample, those who reported feeling most guilty about having sexual fantasies during intercourse (1 SD or more above the mean, n = 39) were compared to those who felt least guilty (1 SD or more below the mean, n = 43). Those subjects who felt guilty reported having significantly fewer sexual fantasies during intercourse than those who felt the least guilty. They also reported higher levels of sexual dissatisfaction and dysfunction. The high-guilt subjects believed that sexual fantasies during intercourse were significantly more abnormal, immoral, uncommon, socially unacceptable, and harmful to themselves, their partner, and their relationship regardless of whether their partner knew that such fantasies occurred. They also reported that the cause of their fantasizing during intercourse reflected significantly more negatively on their sexual behavior and their general character than did the low-guilt group. No statistically significant differences were found between groups on the causal attribution dimensions of internality, stability, or globality of such fantasies. In general, these findings suggest that guilt reactions about sexual fantasies during intercourse are related to beliefs that such fantasies are deviant and harmful and that such guilt reactions are negatively related to sexual satisfaction and adjustment. PMID- 2327896 TI - Rapists and child molesters: psychometric comparisons. AB - The availability of psychosocial treatment for sex offenders is influenced to a considerable extent by the process of adjudication. Convicted rapists are usually incarcerated, and thus receive treatment in a high-structure setting. Convicted child molesters are usually paroled and receive treatment in the low-structure setting of outpatient psychotherapy. In the present study, three types of sex offenders (child molesters, child rapists, and adult rapists) were compared to examine the validity of the match between type of sex offender and type of treatment modality. No differences were found on factor-analytically derived psychological and social historical factor scores between child molesters and child rapists. Adult rapists, however, demonstrated considerably higher levels of pathology characterized by dysphoria, subjective distress, and inhibition, than child molesters and child rapists. The egodystonic psychopathology of the rapists suggests a more favorable prognosis. PMID- 2327897 TI - Sex knowledge, attitudes, and experience of Chinese medical students in Hong Kong. AB - Sex knowledge, attitudes, and experience of 83 Chinese undergraduate medical students were assessed in their responses to the Sex Knowledge and Attitude Test. They were found to be relatively less knowledgeable especially in areas of social and cultural data-based knowledge and were less liberal especially in attitudes toward heterosexual relations and abortion. While increased knowledge tended to be associated with the repudiation of sexual myths, a general conservative outlook as assessed by the Wilson-Patterson Conservatism Scale was found to have the greatest influence on attitudes toward heterosexual relations, autoeroticism, and abortion. In contrast to the sexual practice of young Chinese of similar age based on another survey, the present sample of medical students was relatively heterosexually inexperienced. Implications for medical education with value reorientation are discussed. PMID- 2327899 TI - [2d spring meeting of the Japanese Society of Allergology. Tokyo, 20-21 April 1990. Abstracts]. PMID- 2327898 TI - Feline herpesvirus type 1 glycoproteins eliciting virus neutralizing and hemagglutination-inhibiting antibodies. AB - Monoclonal antibodies (MoAbs) to feline herpesvirus type 1 (FHV-1) were produced to identify the virus-specified immunogenic proteins. When antigens recognized by the MoAbs were investigated by immunoblot and immunoprecipitation assays using FHV-1-infected cell lysate, four groups of immunogenic proteins were identified. MoAbs directed against 60 kDa, 113 kDa, and 143 kDa/108 kDa glycoproteins had virus neutralizing activities, but those against 170 kDa protein did not. Furthermore, MoAbs to the 60 kDa glycoprotein also showed hemagglutination inhibition activity, indicating that this glycoprotein might be the hemagglutinin. PMID- 2327900 TI - Getting involved: the making of an effective governmental affairs program. PMID- 2327901 TI - Statement on assistive personnel to the registered nurse (statement prepared by Tri Council 1/15/90). PMID- 2327902 TI - Radiation oncology in Australia. PMID- 2327903 TI - Computerized tomography mini-series: an alternative to standard paranasal sinus radiographs. AB - Computerized tomography (CT) imaging provides detailed information on the paranasal sinuses that is not available from standard radiographs. The planning and safety of endoscopic sinus surgery is greatly improved by CT imaging. Frequently standard radiographs are ordered because of the reduced cost. The four slice CT Mini-series outlined in this paper provides high resolution bone and soft tissue imaging of the key surgical areas. The Mini-series comprises three precisely placed coronal slices and one axial slice. An average Mini-series takes 20 min to perform at a cost of $NZ66.00. Standard radiographs take up to 30 min to perform at a cost of $NZ38.00. PMID- 2327904 TI - Radiation oncology in Australia: the horns of a dilemma. PMID- 2327905 TI - Role of fine needle aspiration cytology in the management of thoracic lesions. AB - Fine needle aspiration cytology was performed on 121 occasions in 100 patients with various thoracic lesions. The investigation was performed chiefly with the help of straight and lateral chest skiagrams regardless of the size or depth of the lesion. The cellular yield was 87.6%. Positive diagnosis of malignancy could be made in 50 cases. The histopathological correlation in malignant cases was 80%. Non-malignant cytology including neoplastic and inflammatory pathology was also found useful in patient management. This report highlights the versatile role of this procedure in arriving at a diagnosis and planning the treatment for malignant as well as non-malignant thoracic diseases. PMID- 2327906 TI - Problems and limitations with fine needle aspiration cytology of solitary thyroid nodules. AB - Fine needle aspiration cytology (FNAC) is a widely employed tool in the investigative work-up of patients with single thyroid nodules. Although its advantages are well documented, the limitations and problems in interpretation of FNAC in this condition are not well known. Experience with FNAC in 150 patients with solitary thyroid nodules is presented, highlighting the pitfalls of this technique. There was an inadequate specimen rate of 22.7% which declined with increasing experience. Follicular carcinomas could not be differentiated from follicular adenomas by cytology. Difficulties may arise in the detection of papillary carcinomas due to occult lesions, mixed papillary and follicular carcinomas or due to associated thyroid pathology. False positivity is, however, much rarer and is generally due to cellular adenomatous goitres with marked papillary activity. In view of these cytologic limitations, care must be exercised by the treating physician in interpreting cytological results. PMID- 2327907 TI - Model of orthotopic renal transplantation in the rabbit. AB - A microsurgical method of orthotopic renal allotransplantation in the rabbit is described, and the results of 179 consecutive procedures are presented. There were 10 (5.5%) deaths within 1 week of transplantation. Early complications included vascular thrombosis (4.4%), and obstruction (6.7%) and fistula formation (0.6%) at the uretero-ureteric anastomosis. This method of end-to-end vascular and ureteric anastomoses is straightforward and, in contrast to other models, does not require occlusion of the recipient inferior vena cava or aorta, use of a long segment of donor ureter, or operation on the recipient bladder. PMID- 2327908 TI - Vascularized fibular osteocutaneous graft: surgical technique and clinical study. AB - This paper presents a detailed description of the dissection of the vascularized fibular osteocutaneous graft. The fibular graft is vascularized by the peroneal artery. A cutaneous vessel takes origin from the peroneal artery within 2 cm of the fibular midpoint in more than 90% of legs. The reliability of this vessel allows a skin island to be transferred with bone, to act as a monitor of vascularity and provide for skin loss. Ten clinical cases confirmed the reliability of the surgical dissection when centred at the midpoint of the fibula. PMID- 2327909 TI - Duplication of the male urethra associated with crossed renal ectopia. AB - We report two cases of urethral duplication presenting with profound infravesical obstruction at birth. In both cases, left-to-right crossed renal ectopia was also present. PMID- 2327910 TI - Frontal sinus osteoma with complicating intracranial aerocele. AB - An elderly man, who presented initially with clinical features of dementia, was found to have an intracranial tension aerocele due to an underlying osteoma of the frontal sinus. Plain skull roentgenograms and computerized tomography did not reveal the osteoma, although a communication between the frontal sinus and the aerocele was present. Surgical aspiration of the aerocele and excision of the osteoma produced an excellent clinical result. PMID- 2327911 TI - Subarachnoid haemorrhage due to cauda equina haemangiopericytoma. AB - A case of cauda equina haemangiopericytoma presenting with spinal subarachnoid haemorrhage is reported. The tumour had been asymptomatic until 2 weeks prior to presentation, and resulted in complete paraplegia below L3. The authors underline the uncommon association of spinal subarachnoid haemorrhage and cauda equina tumour and the rare finding of a cauda equina haemangiopericytoma. PMID- 2327912 TI - Socio-economics of surgery. PMID- 2327913 TI - Post-choledochoenterostomy 'sump syndrome'. AB - The 'sump syndrome' is an uncommon, late complication of a side-to-side choledochoenterostomy. Five patients with this syndrome were encountered over a 5 year period. Pain or cholangitis was the clinical presentation in four patients, whereas one patient presented with secondary septic arthritis and a hepatic abscess. Liver function tests were mildly abnormal in each patient. All patients had a stomal size of less than 1 cm as assessed by forward- or side-viewing endoscopy. Endoscopic retrograde cholangiography revealed either stones or debris in the distal common bile ducts of all patients. Four patients had a surgical clearance of their duct with concurrent closure of the choledochoduodenostomy in three patients and the creation of a Rouxen-Y end-to-side choledochojejunostomy in the fourth patient. The other patient had an endoscopic sphincterotomy performed. After 1-4 years of follow-up, four patients have had a total resolution of symptoms. The other patient with follow-up for 4 years has had one episode of cholangitis which resolved rapidly with antibiotic treatment. The pathogenesis and clinical spectrum of the sump syndrome are reviewed and current management strategies are discussed. PMID- 2327914 TI - Management of anorectal abscesses: comparison between traditional incision and packing and de Pezzer catheter drainage. AB - This study compares the results of de Pezzer catheter drainage of anorectal abscess with the more traditional technique of incision and packing. A prospective study from this department in 1987 detailed the outcome of patients with anorectal abscess managed routinely by de Pezzer catheter drainage. Ninety one patients were treated, 18 required general anaesthesia, the mean hospital stay was 1.4 days, and 24% subsequently required fistula surgery. A retrospective study has now been undertaken of all patients admitted to Wellington Hospital with anorectal abscess during the same period who were treated by incision and packing. Of 54 patients treated, all had general anaesthesia, the mean hospital stay was 4.5 days, 63% needed district nursing care after discharge and 25% required fistula surgery. Simple de Pezzer drainage is not only safe, convenient and well tolerated by patients, but it compares very favourably with the more traditional method of treating anorectal abscesses and, as a consequence of the minimal hospital care necessary, it must necessarily be a much cheaper method of treatment. PMID- 2327915 TI - Early post-irradiation bowel obstruction managed by longitudinal serotomy. AB - Small bowel obstruction is an uncommon complication that can occur within weeks of pelvic radiotherapy. Probably due to acute inflammation and oedema of the bowel wall, it settles with conservative management. An instance of complete small bowel obstruction occurring 3 months after completion of pelvic radiotherapy is reported. The obstruction failed to resolve; careful longitudinal serotomy allowed the kinking in the bowel to be straightened and, at 1 year follow-up, there were no symptoms of recurrence. PMID- 2327916 TI - Successful surgical management of a case of pulmonary and pericardial melioidosis. AB - A 35 year old diabetic presented with features of septicaemia and developed cardiac tamponade. He was found to have pulmonary, acute septicaemic and pericardial melioidosis. Some initial improvement was achieved with medical therapy but only with surgical intervention was a successful outcome achieved. PMID- 2327917 TI - Resorption of intraspinal fragments of displaced bone graft following anterior spinal fusion. AB - A case of accidental graft protrusion into the intervertebral foramen following anterior spinal fusion is presented. The displaced graft resorbed spontaneously over a 12-month period and neurological deficit resolved. PMID- 2327918 TI - Feasibility of sigmoidoscopic screening for colorectal cancer in the Hunter Region. AB - The success of a cancer detection programme depends on the co-operation of the target population. The aim of this study was to identify factors which might influence those at average and at higher risk of developing colorectal cancer to undergo a sigmoidoscopic screening test if offered. This was addressed by means of a household survey of individuals aged 40 years and over. Overall consent to undergo screening approximated 45%. There was a significant relationship between agreement to sigmoidoscopy and each of the following: age, marital status, educational level attained, and a previous episode of rectal bleeding. Individuals who had undergone sigmoidoscopy in the past were less willing to have the test performed again. Although individuals with a family history of bowel cancer in first-degree relatives perceived themselves as being more likely to develop colorectal cancer, this had no apparent impact on their willingness to have the test. The implications of these findings for community education programmes directed at colorectal cancer are discussed. PMID- 2327919 TI - Epidemiology of alimentary cancers in New South Wales, 1973-82. AB - Incidence and mortality data from New South Wales (NSW) for 1973-82 were examined using log-linear regression to determine the temporal trends of cancers of the alimentary tract. There were significant increases in incidence of cancers of the colon (1.7%/year), rectum (2.6%/year), and liver (4.0%/year) and decreases for cancers of the oesophagus (-2.2%/year) and stomach (-1.4%/year). By contrast, the mortality decreased significantly for cancers of the colon (-1.0%/year) and pancreas (-1.4%/year) as well as for cancers of the oesophagus (-3.4%/year) and stomach (-4.1%/year). Cancers of the colon, rectum and oesophagus were generally less frequent, and cancer of the stomach was more frequent, among migrants to NSW than among the native-born Australians in NSW. This pattern was most evident in migrants from Greece, Italy, Yugoslavia and England and was absent in migrants from Scotland and New Zealand. When compared with the state as a whole, rural NSW had significantly lower incidences of cancers of the oesophagus, stomach, colon and rectum. PMID- 2327920 TI - Superficial (early) gastric cancer. AB - A review of superficial gastric cancer (SGC) has been carried out. Data on the 20 cases who underwent surgery in the 6 years 1982-87 were obtained. The diagnosis of malignancy was established histologically preoperatively in 95% of cases, although more than one endoscopy was required in 50%. In 75%, the primary was confined to the mucosa and in the remainder it had penetrated the submucosa. Lymph node metastases were present in 20%, but distant metastases were not detected. There were no postoperative deaths, and no patient was diagnosed as having recurrent disease during a median follow-up period of 33 months. PMID- 2327921 TI - Do patients have the right to infect their doctor? PMID- 2327922 TI - Efficacy of double versus single gloving in protecting the operating team. AB - Double-glove perforation rates and perforation rates in standard single-gloved operating teams were compared, in order to determine whether double gloving provides additional protection for the operating team. Patients were randomized to undergo surgery with a double-gloved or single-gloved operating team. All gloves worn during the operation were tested for perforations by water-filling and individual digital distension; 115 single-gloved operations and 103 double gloved operations were performed. There were 841 individual operating team members 'at risk'. In the single-glove group, 20.8% of individuals had perforations, but only 2.5% had perforations in both inner and outer gloves (dual perforation) in the double-glove group (P less than 0.0001). The surgeon was most at risk of glove perforation (34.7% of cases in the single-glove group, 3.8% dual perforation in the double-glove group). Longer operations were associated with increased risk of glove perforation. Double-gloving significantly reduces the risk of skin contamination by blood and body fluids and is recommended for all high risk cases. PMID- 2327923 TI - Vascular complications following orthotopic liver transplantation. AB - During the first 3 years of the Australian National Liver Transplantation Programme, 51 liver grafts were performed in 46 patients. There were 11 major vascular complications encountered following 10 liver transplants in eight (17%) patients. They caused death in three patients and the need for retransplantation in two others. Hepatic artery thrombosis (HAT) occurred five (10%) times, producing a spectrum of clinical illness ranging from death to an asymptomatic event. Other vascular complications included hepatic artery stenosis not complicated by thrombosis (two), primary (one) and secondary (one) haemorrhage, thrombosis of a mesoportal venous graft (one) and inferior vena caval stenosis (one). Vascular complications are a significant cause of morbidity and mortality following liver transplantation. Predisposing and precipitating factors should be recognized and minimized. PMID- 2327924 TI - Elective aneurysm repair and the incidence of aortic rupture in an ageing population. AB - During the period January 1984-July 1988, 191 abdominal aortic aneurysms were encountered at Gosford District Hospital, NSW, a hospital that services an ageing population. These aneurysms were either repaired or found as the cause of death at post-mortem. During the study, the rate of elective repair rose from 0.25/month during the first 2 years to 3.67/month in the latter 2.5 years. The mortality for repair of non-ruptured aneurysms was 0.9% compared with 55% for ruptured aneurysms. The 15-fold increase in elective repair resulted in the 58% reduction in the incidence of abdominal aortic rupture from 1.87/month to 0.79/month. The mortality rate from known aneurysms fell from 46% to 14% in the final 2 years. Elective aneurysm repair reduces the incidence of and death from abdominal aortic rupture in an ageing population. PMID- 2327925 TI - Changes in body protein composition following aortic reconstruction. AB - Major surgery initiates a stress response due to the body's neuroendocrine reaction which leads to a breakdown of muscle protein with an increased urinary nitrogen excretion and a negative nitrogen balance. In vivo neutron activation analysis (IVNAA) is a technique which measures total body nitrogen. A total of 23 IVNAA studies were performed in six patients having aortic reconstruction to assess the effect of this major operation on body nitrogen and to determine the time required for a return to the pre-operative state. Aortic surgery caused a mean decrease of 2.9% in bodyweight (from a mean of 65.4 kg to 63.5 kg) but a much greater decrease of 9.9% in total body nitrogen (from a mean of 1778 g to 1602 g). Only two of six patients had recovered to pre-operative values by the end of the study period which extended for a mean of 92 days. PMID- 2327927 TI - Liver retraction using elastic bands. PMID- 2327926 TI - Intra-abdominal pressure and renal function after surgery to the abdominal aorta. AB - It has been suggested that an elevated intra-abdominal pressure (IAP) can impair renal function. In a prospective longitudinal study, the IAP of 42 patients admitted to an intensive care unit after abdominal aortic surgery was monitored. When compared with the other patients, the 22 patients (53%) who developed renal impairment had higher IAP (17.8 +/- 6.0 mmHg versus 14.1 +/- 4.8 mmHg; P less than 0.01) and APACHE II scores (15.6 +/- 6.0 versus 9.8 +/- 4.6; P less than 0.01). Each of the 10 patients who were re-explored because of haemodynamic instability and oliguria had an IAP of greater than 18 mmHg (positive predictive value = 85%, negative predictive value = 62%). Following re-exploration, the urinary output increased by 115 +/- 40 mL/h (P less than 0.01), and the IAP decreased by 10 +/- 3 mmHg (P less than 0.01). Although it is concluded that an IAP greater than 18 mmHg is a significant risk factor for the development of impaired renal function, it was not possible to prove a causal relationship between these events. Nevertheless, such a relationship has been demonstrated in animal and human models. PMID- 2327928 TI - AIDS and Salmonella-infected abdominal aortic aneurysm. AB - The case of a bisexual male patient with acquired immunodeficiency syndrome (AIDS) and an infected abdominal aortic aneurysm requiring surgery is presented. Attention is drawn to the fact that an unpredictable number of operations will be needed in AIDS patients in the next future. PMID- 2327929 TI - Total excision of mucinous biliary cystadenoma. AB - In the past year, total excision of mucinous biliary cystadenomas was carried out in three patients by shelling these lesions out from the liver substances. Formal hepatic resection was unnecessary. As any previous surgical procedure on the cyst will make subsequent excision technically more difficult, or even impossible, it is believed that excision should be carried out at the initial operation. Thus, a correct pre-operative or intra-operative diagnosis is important. This requires a high index of clinical suspicion, an adequate pre-operative work-up and an appropriate use of intra-operative ultrasound and frozen section to differentiate these lesions from other cystic lesions of the liver. PMID- 2327930 TI - Leiomyomatosis peritonealis disseminata. AB - A 49 year old woman presented with leiomyomatosis peritonealis disseminata (LPD) which is a benign and very rare disease entity. This patient is particularly interesting because she presented with many atypical features. She is the second Oriental case reported, and the follow-up period was long. The disease was symptomatic and progressive despite bilateral salpingo-oophorectomy, hysterectomy and repeated excision of all the recurrent nodules. She had documented recurrences of LPD in three episodes at 4 years apart. There was no obvious systemic hormonal abnormality including pregnancy or oestrinizing granulosa tumour, and she had never taken any contraceptive drugs. The importance of differentiation of this condition from generalized metastatic intra-abdominal malignancy is discussed as LPD has a very good prognosis. PMID- 2327931 TI - The effects of contingent music and differential reinforcement on infantile colic. AB - Infantile Colic is a behavioral syndrome characterized by paroxysms of excessive crying and increased motor activity, hypertonicity of the musculature, excessive flatus and erratic sleeping and feeding patterns. Ten to 40% of all infants are diagnosed as having Colic. The medical evidence to date does not justify any conclusions regarding the etiology or treatment of Colic. Typically, parents are advised to simply wait until Colic has run its course which is often 3-4 months. The behavioral program reported here was designed to increase behavior that competed with crying by reinforcing quiet alertness with music and parental attention. Concurrently, it attempted to inhibit excessive crying by a brief time out procedure. A group of 8 infants diagnosed as Infant Colic were included in this study. The dependent variable, crying, was measured through direct observations based on hourly samples involving 30 observations of 2-min intervals. The independent variable consisted of a behavioral treatment package. A within-S reversal design was used to assess the functional properties of the treatment. The results show that across all 8 infants the introduction of the treatment package led to a substantial decrease in excessive crying of about 75% of the initial baseline. Further, a functional relationship was identified between the treatment and excessive crying behavior: crying decreased when the treatment was initially introduced, it resumed when the treatment was withdrawn and decreased again when the treatment was reinstated. PMID- 2327932 TI - Panic disorder: cognitive-behavioral treatment. AB - The effectiveness of an integrated treatment program utilizing cognitive behavioral therapies for Panic Disorder was examined. Treatment was comprised of Cognitive Model of Panic-derived procedures, Cognitive Therapy and Applied Relaxation Training. Subjects meeting DSM-III-R criteria for Panic Disorder received thirteen 2.5-hr sessions of outpatient therapy in small groups, over a 12-week period. Subjects were given an extensive rationale of the etiology, development and maintenance of Panic Disorder, within the framework of the Cognitive Model of Panic, and controlled behavioral experiments in panic evocation to internal panicogenic cues, cognitive reappraisal of somatic and ideational cues, breathing retraining, Applied Relaxation Training and Cognitive Therapy to identify and remediate maladaptive beliefs and dysfunctional cognitive schemas. A comprehensive assessment battery was given at pre-mid-post-treatment which included measures of tripartite functioning, global severity, panic, fear, anxiety, depression and psychiatric symptomatology. Analyses indicated statistically significant improvements across all outcome domains. All subjects were free of spontaneous (uncued) panic attacks at post-treatment, and all met operationalized criteria for high endstate functioning. These findings are discussed, with recommendations for future research. PMID- 2327933 TI - The effects of cued UCS rehearsal on the retention of differential 'fear' conditioning: an experimental analogue of the 'worry' process. AB - This study describes a human electrodermal conditioning experiment in which subjects were asked to mentally rehearse the UCS in a period following initial fear conditioning and prior to a test period involving nonreinforced presentations of the CS. Subjects who were asked to rehearse the UCS retained a differential fear CR during subsequent unreinforced presentations of the CS, but control subjects who were asked to rehearse either a nonaversive event or an aversive event unrelated to the UCS failed to retain the differential CR they had acquired during conditioning. These results suggest that rehearsal of the UCS during periods when CS and UCS are absent can aid the persistence of a fear CR in the absence of further pairings of the CS and UCS. It is argued that these effects can be explained in terms of the effect of UCS rehearsal on the strength and evaluation of the UCS representation. It is also suggested that cued UCS rehearsal might provide a useful procedure for understanding clinical incubation effects and for understanding how the 'worry' process contributes to the maintenance and incubation of fear. PMID- 2327934 TI - Predicting outcome of chronic pain treatment via a modified self-efficacy scale. AB - This study utilized a modified self-efficacy scale and examined the relationship of perceived self-efficacy to treatment outcome in a chronic, intractable, benign pain population (N = 62). In two separate studies a self-efficacy scale was given to inpatients in a combined cognitive-behavioral and medical treatment program. The scale categories consisted of (1) walking distance, (2) lifting ability, (3) pain coping, (4) working ability, and (5) social and recreational engagement. Self-efficacy beliefs were found to be associated with the level of functioning of these patients and their response to treatment. Patients with higher self efficacy scores following treatment rated themselves as more improved and demonstrated better overall functioning with greater reductions in chronic illness behavior at followup. These observations support the merits of self efficacy measures as predictors of treatment outcome in chronic pain patients. PMID- 2327935 TI - Students' self-ratings of stress in medical school: a replication across 20 months. AB - We replicated the essential results of a prior study on the capacity of the BAROMAS scales to reflect stress in medical school as perceived by students. As before, subjective stress was high at the start of medical school, and when facing the exams prerequisite to entry into clinical clerkships. On most measures, stress was lowest when the second year began (i.e. after having passed the first). Once again, most test-retest reliabilities (significant rs ranged from 0.24 to 0.66 for confidence ratings at 12- and 20-months after entry) were moderate. PMID- 2327936 TI - A living systems approach to understanding the concept of stress. AB - In this article, the basic concepts used in conceptualizing stress and classifying its related phenomena are defined and a general conceptual framework for understanding the interrelationships among these concepts is proposed. The conceptual scheme described is intended to be applicable across disciplines including the biological and the behavioral and social sciences. This model is based largely on the living systems theory developed by Miller (1978) and the work of Selye (1950). It provides a coherent conceptual framework in which studies in the various disciplines engaged in stress research can be organized and integrated. Its use across disciplines will facilitate the sharing of information and prevent needless duplication of effort by researchers in different fields. It will also facilitate the generation and formulation of empirically testable hypotheses (including specific cross-level hypotheses), the development of more focused research designs and a clearer interpretation of findings. By understanding at which point in the stress pathway a system is when observed, a clearer picture of both the biological mechanisms involved and the psychosocial ramifications of stress may be obtained. As a consequence of this type of information becoming available, more optimal treatments for patients with stress-related disorders can be developed. PMID- 2327937 TI - Antimutagenesis and anticarcinogenesis mechanisms II. Proceedings of the second international conference. December 4-9, 1988, Ohito, Japan. PMID- 2327938 TI - Carcinogenicity and modification of carcinogenic response by antioxidants. PMID- 2327939 TI - Antimutagenic activity of vitamins in cultured mammalian cells. AB - Cultured mammalian cell systems are useful for examining the quantitative effects of mutagens and antimutagens on cell survival and gene mutations and the mechanisms of the interaction of two chemicals in the process of mutation induction. In the present article, the antimutagenic effects of vitamins C, E, and A, and derivatives of vitamin C on EMS-induced 6TG-resistant mutations in Chinese hamster V79 cells were examined. Vitamin C was most effective in inhibiting EMS-induced cytotoxicity and 6TG-resistant mutations. In the presence of vitamin C at a concentration of 100 micrograms/ml, EMS-induced mutations were reduced to about one-third or one-fourth of those in control cultures treated with EMS alone. Dehydro-vitamin C and iso-vitamin C also inhibited EMS-induced mutations to about one-half or one-third of the control level. The fact that vitamin C was effective in reducing EMS-induced mutations when EMS was previously incubated together with vitamin C for 3 hr suggests that vitamin C may react directly with EMS as a desmutagen and thus inactivate its mutation-inducing activity in Chinese hamster V79 cells. Vitamin E had an additive cytotoxic effect on EMS-induced cytotoxicity. This vitamin enhanced the frequencies of 6TG resistant mutations induced by EMS. Pretreatment with vitamin E before treatment with EMS resulted in no detectable effect in modifying the EMS-induced mutations. On the contrary, vitamin A markedly enhanced EMS-induced mutation frequencies. PMID- 2327940 TI - Permanent conversion of NIH3T3 cells transformed by activated c-Ha-ras, c-Ki-ras, N-ras, or c-raf, and of human pancreatic adenocarcinoma containing activated c-Ki ras to apparently normal cells by treatment with the antibiotic azatyrosine. PMID- 2327942 TI - The mouse mutant, "wasted": tissue-specific radiation sensitivity and hematopoietic cell lineages. PMID- 2327941 TI - Inhibition of tobacco-specific nitrosamine 4-(methyl-nitrosamino)-1-(3-pyridyl)-1 butanone (NNK)-induced lung tumors and DNA methylation in F344 rats and A/J mice by phenethyl isothiocyanate. PMID- 2327943 TI - Antimutagenic effects of dimethyl sulfoxide on metabolism and genotoxicity of benzene in vivo. PMID- 2327944 TI - Possible antitumor promoter in the glandular stomach: calcium chloride. AB - Studies were made on the inhibitory effects of CaCl2 and 13-cis-retinoic acid on induction of replicative DNA synthesis (RDS) in the pyloric mucosa of male F344 rats by the glandular stomach tumor promoter, NaCl. RDS in the pyloric mucosa showed a maximum of about a ten-fold increase 17 hr after administration of 3.3 M NaCl and returned to the control level 48 hr after the administration of NaCl. Administration of 400 mM CaCl2 1 hr before NaCl resulted in 60-80% inhibition of the increase in RDS 4-48 hr after NaCl administration. Administration of 20 to 400 mM CaCl2 1 to 2 hr before NaCl caused dose-dependent inhibition of the increase in RDS 17 hr after NaCl administration, with 400 mM CaCl2 causing 80 100% inhibition. Administration of 400 mM CaCl2 1 hr before NaCl also decreased the histological damage of the surface epithelial cells induced by NaCl. Administration of 13-cis-retinoic acid at doses of 10 micrograms-10 mg/kg body weight did not inhibit the increase in RDS in the pyloric mucosa that was induced by NaCl. These results suggest that CaCl2, but not 13-cis-retinoic acid, inhibits tumor promotion in the pyloric mucosa of rat stomach. PMID- 2327945 TI - Inhibitory effects of chlorogenic acid, reserpine, polyprenoic acid (E-5166), or coffee on hepatocarcinogenesis in rats and hamsters. AB - Four different experiments were performed in order to examine the modifying effects of chlorogenic acid (CA), reserpine, polyprenoic acid (E-5166), and coffee on chemical carcinogenesis in rats or hamsters. Experiment 1: The numbers of hyperplastic liver cell foci and the incidence of colon tumors in male and female Syrian golden hamsters given a single intravenous injection of methylazoxymethanol (MAM) acetate and then fed the diet containing 0.025% CA for 24 wk were significantly lower than those of hamsters given MAM acetate alone. Experiment 2: The incidence of altered hepatocellular foci in female ACI/N rats given N-2-fluorenylacetamide (FAA, 0.02% in diet) for 10 wk and reserpine (weekly subcutaneous injections, 1 microgram/g body weight) during or after (17 wk) FAA exposure was significantly lower than that of rats given FAA alone. Experiment 3: The number of hepatocellular foci in male ACI/N rats given 0.02% FAA diet for 13 wk and E-5166 by gavage (40 mg/kg body weight, 3 times/wk) for 16 wk after the end of FAA exposure was significantly smaller than that in rats given FAA diet alone. Experiment 4: Incidences of liver tumors and hepatocellular foci of rats given concurrent dietary administration of aminopyrine (0.01%) and sodium nitrite (0.1%) and coffee solution as a drinking water for 630 da were significantly lower than those of rats given aminopyrine and sodium nitrite. Thus, the tested compounds had inhibitory effects on chemical carcinogenesis in liver or colon. PMID- 2327946 TI - Influence of potential antioxidants on free-radical damage of lymphocytes. PMID- 2327948 TI - Classification of mechanisms of inhibitors of mutagenesis and carcinogenesis. PMID- 2327947 TI - Specificity of antimutagens against chemical mutagens in microbial systems. AB - Procedures have been developed which enable the study of antimutagenic specificity of certain antimutagenic chemicals against chemical mutagens/carcinogens. Modifications of the Ames Salmonella assay, the Bacillis subtilis rec assay of Kada and co-workers, and the Luria-Delbruck fluctuation test, along with procedures we have developed utilizing E. coli K12 strain ND160 developed by Dworkin, all are employed in these studies. Using these procedures, a number of naturally-occurring compounds and/or their derivatives have been shown to produce antimutagenic specificity either against changes at different specific genetic loci or against activity of specific chemical mutagens such as nitrofurazone, ethyl methanesulfonate, or caffeine. Compounds that demonstrate this activity include cinnamaldehyde, chlorophyllin, an extract of Glycyrrhiza glabra, spermine, and mixtures of guanosine and cytidine. The data demonstrate that some antimutagens act specifically against spontaneous mutations, while others inhibit the development of chemically-induced mutations at specific loci. These results have potential application to the prevention of chemical toxicological damage. PMID- 2327949 TI - Factors affecting penetration of retrograde coronary venous injections into normal and ischemic canine myocardium: assessment by contrast echocardiography and digital angiography. AB - Ths experimental study described myocardial echo contrast enhancement through coronary venous injections. Retrograde administration of renografin was performed in 15 closed-chest dogs. Two-dimensional echocardiography was used to study myocardial echo contrast enhancement before and after coronary artery occlusion. Digital subtraction venography was used to assess delivery, drainage and shunting of the retrograde injectate. Systolic/diastolic blood pressure in the great cardiac vein measured 7 +/- 3/1 +/- 0.6 mm Hg and increased to 29 +/- 11/5 +/- 3 after coronary sinus occlusion and to 55 +/- 2.3/15 +/- 12 mm Hg during coronary sinus contrast injection. Myocardial contrast echo appearance in a midpapillary left ventricular short axis cross-section was limited to the anteroseptal region, extending to 28.4 +/- 11.3% of the section circumference after great cardiac vein injections and 35.3 +/- 17% after coronary sinus injections (difference NS). After occlusion of the left anterior descending coronary artery, great cardiac vein contrast injections resulted in opacification of 36.6 +/- 9.7% of the section circumference (N.S. vs preocclusion control) and opacified most, but not all asynergic segments. After occlusion of the circumflex coronary artery, myocardial echo contrast uptake was restricted to the septum and the anterior wall. The ischemic and asynergic posterolateral myocardial segments were not opacified. Digital subtraction coronary venography revealed rapid drainage of retrogradely injected contrast to the right atrium, in spite of coronary sinus balloon occlusion via venovenous anastomoses. Retrograde coronary venous contrast injections may help define myocardial regions which are accessible with retrograde coronary venous interventions. PMID- 2327950 TI - Antiischemic effects of alinidine in paced isolated rat hearts. AB - Low-flow perfusion of paced (5 Hz) rat heart Langendorff preparation with Tyrode solution for 60 min caused a reduction or disappearance of left ventricular pressure amplitude. After 60 min of low-flow perfusion myocardial concentrations of high energy phosphates, as well as the energy charged potential, were diminished while lactate accumulated. Infusion of alinidine into the perfusate at low-flow conditions, resulted in a mean concentration of 15.0 +/- 0.60 microM, and prevented the mechanical and biochemical changes of low-flow perfusion, thus indicating maintenance of aerobic metabolism under hypoxic conditions. These heart rate-independent cardioprotective effects of the "specific bradycardic" drug alinidine are discussed in light of the adenosine antagonistic actions of this compound which should prevent coronary steal. PMID- 2327951 TI - Acute hemodynamic effects of coronary artery ligation in conscious rats. AB - Because of the growing interest in the use of coronary artery ligation (CAL) in rats as a model for studies on heart failure, we have investigated the acute hemodynamic changes following CAL in conscious rats. Animals were equipped for measurement of cardiac output (CO), arterial pressure (MAP), and central venous pressure (CVP). These parameters were measured before CAL, immediately after, and 24 h after. Furthermore, peak CO, obtained by rapid infusion of 12 ml Ringer's solution (in 1 min) was measured 2 days before and 1 day after CAL. CAL resulted in immediate reduction of CO, because of reduced stroke volume (SV). CO as well as SV were inversely correlated with infarct size as determined 24 h after CAL. Heart rate (HR) and MAP did not change. Twenty-four hours later, CO was still reduced. MAP was now reduced, possibly as a result from resetting of nervous reflex mechanisms. Before CAL, peak CO and SV were similar in CAL and sham animals. At 24 h after CAL, these parameters were greatly reduced in CAL rats. Peak values were strongly correlated to infarct size. Results indicate that CAL in rats leads to hemodynamic changes similar to the ones observed following myocardial infarction in man. Cardiac function is related to infarct size and is altered both at rest and during maximal stimulation. PMID- 2327952 TI - NADP(+)-dependent D-xylose dehydrogenase from pig liver. Purification and properties. AB - An NADP(+)-dependent D-xylose dehydrogenase from pig liver cytosol was purified about 2000-fold to apparent homogeneity with a yield of 15% and specific activity of 6 units/mg of protein. An Mr value of 62,000 was obtained by gel filtration. PAGE in the presence of SDS gave an Mr value of 32,000, suggesting that the native enzyme is a dimer of similar or identical subunits. D-Xylose, D-ribose, L arabinose, 2-deoxy-D-glucose, D-glucose and D-mannose were substrates in the presence of NADP+ but the specificity constant (ratio kcat./Km(app.)) is, by far, much higher for D-xylose than for the other sugars. The enzyme is specific for NADP+; NAD+ is not reduced in the presence of D-xylose or other sugars. Initial velocity studies for the forward direction with xylose or NADP+ concentrations varied at fixed concentrations of the nucleotide or the sugar respectively revealed a pattern of parallel lines in double-reciprocal plots. Km values for D xylose and NADP+ were 8.8 mM and 0.99 mM respectively. Dead-end inhibition studies to confirm a ping-pong mechanism showed that NAD+ acted as an uncompetitive inhibitor versus NADP+ (Ki 5.8 mM) and as a competitive inhibitor versus xylose. D-Lyxose was a competitive inhibitor versus xylose and uncompetitive versus NADP+. These results fit better to a sequential compulsory ordered mechanism with NADP+ as the first substrate, but a ping-pong mechanism with xylose as the first substrate has not been ruled out. The presence of D xylose dehydrogenase suggests that in mammalian liver D-xylose is utilized by a pathway other than the pentose phosphate pathway. PMID- 2327953 TI - A re-appraisal of the structural basis of stereochemical recognition in papain. Insensitivity of binding-site-catalytic-site signalling to P2-chirality in a time dependent inhibition. AB - 1. 2-(N'-Acetyl-D-phenylalanylamino)ethyl 2'-pyridyl disulphide (compound I) [m.p. 123-124 degrees C; [alpha]20D -7.1 degrees (c 0.042 in methanol)] was synthesized, and the results of a study of the pH-dependence of the second-order rate constant (k) for its reaction with the catalytic-site thiol group of papain (EC 3.4.22.2), together with existing kinetic data for the analogous reaction of the L-enantiomer (compound II), were used to evaluate the consequences for transition-state geometry of the difference in chirality at the P2 position of the probe molecule. 2. The kinetic data suggest that the D-enantiomer binds approx. 40-fold less tightly to papain than the L-enantiomer but that the binding site--catalytic-site signalling that results in a (His-159)-Im(+)-H-assisted transition state occurs equally effectively in the interaction of the former probe as in that of the latter. This results in pH-k profiles for the reactions of both enantiomers each characterized by four macroscopic pKa values (3.7-3.9, 4.1-4.3, 7.9-8.3 and 9.4-9.5) in which k is maximal at pH approx. 6 where the Im(+)-H-assisted transition state is most fully developed. 3. Model building indicates that both enantiomers can bind to papain such that the phenyl ring of the N-acetylphenylalanyl group makes hydrophobic contacts in the binding pocket of the S2 subsite with preservation of the three hydrogen-bonding interactions involving the substrate analogue reagent and (Asp-158) C = O, (Gly-66) C = O, and (Gly-66)-N-H of papain. Earlier predictions that binding of N-acyl-D phenylalanine derivatives to papain would be prevented on steric grounds [Berger & Schechter (1970) Philos. Trans. R. Soc. London B 257, 249-264; Lowe & Yuthavong (1971) Biochem. J. 124, 107-115; Lowe (1976) Tetrahedron 32, 291-302] were based on assumed models that are not consistent with the X-ray-diffraction data for papain inhibited by alkylation of Cys-25 with N-benzyloxycarbonyl-Phe-Ala chloromethane [Drenth, Kalk & Swen (1976) Biochemistry 15, 3731-3738]. 4. The possibility that the kinetic expression of P2-S2 stereospecificity may depend on the nature of the chemistry occurring in the catalytic site of papain is discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2327954 TI - Dependence of the P2-S2 stereochemical selectivity of papain on the nature of the catalytic-site chemistry. Quantification of selectivity in the catalysed hydrolysis of the enantiomeric N-acetylphenylalanylglycine 4-nitroanilides. AB - 1. N-Acetyl-L-phenylalanylglycine 4-nitroanilide and its D-enantiomer were synthesized and characterized and used as substrates with which to evaluate stereochemical selectivity in papain (EC 3.4.22.2)-catalysed hydrolysis. 2. Kinetic analysis at pH 6.0, I 0.1, 8.3% (v/v) NN-dimethylformamide and 25 degrees C by using initial-rate data with [S] much less than Km and weighted non-linear regression provided values of kcat./Km for the catalysed hydrolysis of both enantiomers as (kcat./Km)L = 2040 +/- 48 M-1.S-1 and (kcat./Km)D = 5.9 +/- 0.07 M 1.S-1. These data, taken together with individual values of kcat. and Km for the hydrolysis of the L-enantiomer (a) estimated in the present work as kcat. = 3.2 +/- 1.2 S-1 and Km = 1.5 +/- 0.6 mM and (b) reported by Lowe & Yuthavong [(1971) Biochem. J. 124, 107-115] for the reaction at pH 6.0 in 10% (v/v) NN dimethylformamide and 35 degrees C, as kcat. = 1.3 +/- 0.2 S-1 and Km = 0.88 +/- 0.1 mM, suggest that (kcat./Km)L congruent to 2000 M-1.S-1 and thus that (kcat./Km)L/(kcat./Km)D congruent to 330.3. Model building indicates that both enantiomeric 4-nitroanilides can bind to papain such that the phenyl ring of the N-acetylphenylalanyl group makes hydrophobic contacts in the S2 subsite with preservation of mechanistically relevant hydrogen-bonding interactions and that the main difference is in the positioning of the beta-methylene group. 4. The dependence of P2-S2 stereochemical selectivity of papain on the nature of the catalytic-site chemistry for reactions involving derivatives of N acetylphenylalanine is discussed. The variation in the index of stereochemical selectivity (ratio of the appropriate kinetic or thermodynamic parameter for a given pair of enantiomeric ligands), from 330 for the overall acylation process of the catalytic act, through 40 and 31 for the reaction at electrophilic sulphur in 2-pyridyl disulphides respectively without and with assistance by (His-159) Im(+)-H, to 5 for the formation of thiohemiacetal adducts by reaction at aldehydic carbon, is interpreted in terms of the extent to which conformational variation of the bound ligand in the catalytic-site region permits the binding mode of the -CH2-Ph group of the D-enantiomer to approach that of the L enantiomer. PMID- 2327955 TI - Activation of inositol phospholipid breakdown by prostaglandin F2 alpha without any stimulation of proliferation in quiescent NIH-3T3 fibroblasts. AB - Stimulation of NIH-3T3 cells with prostaglandin F2 alpha (PGF2 alpha) caused a dose- and time-dependent generation of inositol phosphates. The first detectable changes were in the levels of Ins(1,4,5)P3 and Ins(1,3,4,5)P4. Increases in Ins(1,3,4)P3, InsP2 and InsP were detected later, and only minor changes were observed in putative InsP5 or InsP6. The accumulation of inositol phosphates was synergistically increased by the addition of calf serum, whereas PGF2 alpha had no effects on cell proliferation in either the presence or the absence of calf serum. Stimulation of a different clone of NIH-3T3 cells (AmNIH-3T3) or Swiss 3T3 cells with PGF2 alpha resulted in both inositol phospholipid breakdown and cell proliferation. No differences were found in the characteristics of PGF2 alpha stimulated inositol phosphate generation between the two clones of NIH-3T3 cells, nor was there any difference in receptor number of Kd. These results question the role of inositol phospholipid breakdown in mitogenesis and demonstrate significant differences in the biochemical properties of apparently the 'same' cells. PMID- 2327956 TI - Testosterone-mediated regulation of mouse renal cytochrome P-450 isoenzymes. AB - We have studied the extent to which mouse renal cytochrome P-450 isoenzymes are sexually differentiated, and the factor(s) regulating this dimorphism. Intriguingly, sex differences were not seen in the expression of a single cytochrome P-450 enzyme, but were observed in the expression of all P-450 isoenzymes detectable, encoded by six gene families or sub-families. This effect was mediated by testosterone, which had the capacity to both induce and repress P 450 gene expression, and which was independent of growth hormone. The changes in protein content were mirrored in all but one case by changes in the levels of mRNA, indicating that these genes contain hormone-responsive elements. These findings are consistent with numerous reports of sex differences in the susceptibility of the mouse kidney to the toxic and carcinogenic effects of drugs and environmental chemicals, many of which are metabolized to cytotoxic products by the cytochrome P-450-dependent mono-oxygenases. These data imply that circulating androgen levels will be an important factor in susceptibility of the kidney to toxic or carcinogenic compounds which require metabolic activation. PMID- 2327957 TI - Respiratory inhibitors and uncouplers prevent the aeration-induced increase in mitochondrial anion conductivity. AB - 1. When mitochondria are stirred in air the rate of anion conductivity increases, this effect being enhanced by the addition of respiratory substrate. 2. This effect is reversible if the mitochondria are stored for a period of time under N2. 3. The aeration-induced increase in mitochondrial anion conductivity can also be prevented by the addition of respiratory inhibitors rotenone and antimycin A, as well as by 30 microM-cyanide. 4. A decrease in this aeration-induced anion conductivity can also be observed upon the addition of the uncouplers carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (2 microM) and 2,4-dinitrophenol (100 microM). 5. Simultaneous measurements of mitochondrial anion conductivity and membrane potential show a relationship between the level of membrane potential and anion conductivity. 6. It is suggested that the level of membrane potential is either directly or indirectly responsible for the level of mitochondrial anion conductivity. PMID- 2327958 TI - The supramolecular organization of ovomucin. Biophysical and morphological studies. AB - Ovomucin participates in the ovomucin-gel-forming properties because of its shape and its ability to interact in a specific spatial organization. Purified from chicken egg-white by exclusion chromatography with Sephacryl S-300 and Sepharose CL-2B and analysed by light-scattering, it exhibited an Mr of about 40 x 10(6). This large Mr can be explained by the aggregation of polymers that can be degraded into 3 x 10(6)-Mr fragments by reduction with dithiothreitol. The values for hydrodynamic parameters such as Mr, radius of gyration, hydrodynamic radius, mass per unit length and combinations of them suggested that ovomucin is a linear and highly flexible molecule conferring upon it a random-coil-like structure in 0.2 M-NaCl solution. Analysis of the ovomucin molecules by electron microscopy revealed its linear character but also indicated a lower Mr than that obtained in the light-scattering experiments. By temperature-induced non-specific aggregation of an ovomucin solution containing other globular egg proteins, an attempt was made to find out what conditions are required for gel formation and to examine the quality of aggregation that is obtained under these conditions. Results show that the viscosity of the solution did not increase after heat treatment. Apparently, in the ovomucin gel, specific spatial organization of the ovomucin molecules is required for hydrogel formation. PMID- 2327959 TI - Cobalamin neuropathy. Is S-adenosylhomocysteine toxicity a factor? AB - Cobalamin neuropathy was produced in cape fruit bats (Rousettus aegyptiacus) by a cobalamin-free diet combined with intermittent exposure to nitrous oxide, which inactivates cobalamin. There were no significant differences in S adenosylmethionine/S-adenosylhomocysteine ratios in the central nervous system of cobalamin-deficient and cobalamin-replete bats. Taken with other data there are no grounds of support for a hypothesis that cobalamin neuropathy is the result of impaired methylation, however produced. PMID- 2327960 TI - Receptor-activated calcium entry in exocrine cells does not occur via agonist sensitive intracellular pools. AB - Currently, most models describing receptor-activated Ca2+ entry in exocrine cells invoke a pathway for the entry of extracellular Ca2+ directly linking the agonist sensitive intracellular Ca2+ pools with the plasma membrane. In the avian nasal gland, a model exocrine ion-secreting tissue, we have found that Ca2+ entry during refilling of the intracellular pools following termination of receptor activation (by atropine) occurs via the cytoplasm and not directly into the empty pools. Under appropriate conditions this can be demonstrated as a transient increase in [Ca2+]i (intracellular Ca2+ concn.) seen on restoration of normal extracellular Ca2+ concentrations after atropine to stimulated cells whose intracellular stores have been prevented from refilling by incubation in a low extracellular-Ca2+ medium. The magnitude of these [Ca2+]i transients decays with time, but with a time course markedly slower than for the corresponding decrease in intracellular Ins(1,4,5)P3. Further experiments have revealed that Ca2+ entry into the cytoplasm during the initial stimulation phase is also direct and not via the intracellular pools. Thus the initial rates of increase in [Ca2+]i during stimulation are always faster in conditions where both Ca2+ entry and Ca2+ release occur (i.e. they are additive). These differences could not be explained by any effects of extracellular Ca2+ on the initial increases in intracellular Ins(1,4,5)P3 after addition of carbachol. These data are therefore inconsistent with the current models in which the rate of Ca2+ entry through the agonist sensitive pools cannot exceed the rate of Ca2+ release. It appears therefore that Ca2+ entry and Ca2+ release must occur via separate pathways operating in parallel, and not in series as previously predicted. PMID- 2327961 TI - Insulin-like growth factor binding to the atypical insulin receptors of a human lymphoid-derived cell line (IM-9). AB - The cells of the IM-9 human lymphocyte-derived line contain a sub-population of insulin-binding sites whose immunological and hormone-binding characteristics closely resemble those of the atypical insulin-binding sites of human placenta. These binding sites, which have moderately high affinity for multiplication stimulating activity [MSA, the rat homologue of insulin-like growth factor (IGF) II] and IGF-I, are identified on IM-9 cells by 125I-MSA binding. They account for approximately 30% of the total insulin-receptor population, and do not react with a monoclonal antibody to the type I IGF receptor (alpha IR-3). The relative concentrations of unlabelled insulin, MSA and IGF-I required to displace 50% of 125I-MSA from these binding sites (1:4.7:29 respectively) are maintained for cells, particulate membranes, Triton-solubilized membranes precipitated either by poly(ethylene glycol) or a polyclonal antibody (B-10) to the insulin receptor, and receptors purified by insulin affinity chromatography. Because the atypical insulin/MSA-binding sites outnumber the type I IGF receptors in IM-9 cells by approximately 10-fold, they also compete with the latter receptors for 125I-IGF-I binding. Thus 125I-IGF-I binding to IM-9 cells is inhibited by moderately low concentrations of insulin (relative potency ratios for insulin compared with IGF I are approx. 1/14 to 1/4) and is partially displaced (65-80%) by alpha IR-3. When type I IGF receptors are blocked by alpha IR-3 or removed by B-10 immunoprecipitation or insulin affinity chromatography, the hormone-displacement patterns for 125I-IGF-I binding resemble those of the atypical insulin/MSA binding sites. PMID- 2327962 TI - The changes in hepatic enzyme expression caused by selenium deficiency and hypothyroidism in rats are produced by independent mechanisms. AB - Selenium (Se) deficiency for 5 weeks in rats produced changes in the activity of a number of hepatic, renal and plasma enzymes. In animals whose food intake was restricted to 75% of normal for 2 weeks, Se deficiency produced significant increases in the activity of hepatic cytosolic 'malic' enzyme and mitochondrial alpha-glycerophosphate dehydrogenase (GPD), two enzymes that are particular sensitive to the thyroid-hormone concentrations in tissue. Propylthiouracil induced hypothyroidism produced significant decreases in 'malic' enzyme and GPD activities. The effect of hypothyroidism on the activity of 'malic' enzyme, GPD and other enzymes studied in liver and plasma was often opposite to that seen in Se deficiency. Glutathione S-transferase (GST) activity was increased by both Se deficiency and hypothyroidism, but in hypothyroid animals further significant increases in GST were produced by Se deficiency. These data suggest that the changes in enzyme expression observed in Se deficiency are not caused by decreased tissue exposure to thyroid hormones. PMID- 2327963 TI - Vitamin K-dependent carboxylation. Mechanistic studies with 3-fluoroglutamate containing substrates. AB - The tripeptides t-butyloxycarbonyl-Xaa-Glu-[3H]Val, where Xaa is either (2R,3S)- or (2R,3R)-3-fluoroglutamate (respectively the erythro and the threo isomer), were synthesized and their behaviour during vitamin K-dependent carboxylation was studied. Neither peptide was carboxylated. The erythro compound gave rise to an HF-elimination product representing 1% of the starting material. This HF elimination did not occur during incubation of the threo compound. The formation of the dehydropeptide, probably by elimination of an F- anion from an intermediate carbanion, favours the ionic pathway for vitamin K-dependent carboxylation. PMID- 2327964 TI - Release of purine and pyrimidine nucleosides and their catabolites from the perfused rat hindlimb in response to noradrenaline, vasopressin, angiotensin II and sciatic-nerve stimulation. AB - Uric acid and uracil were released at constant rates (0.95 and 0.4 nmol/min per g respectively) by the perfused rat hindlimb. Noradrenaline, vasopressin or angiotensin II further increased the release of these substances 2-5-fold, coinciding with increases in both perfusion pressure (vasoconstriction) and O2 uptake. The hindlimb also released, but in lesser amounts, uridine, hypoxanthine, xanthine, inosine and guanosine, and all but hypoxanthine and guanosine were increased during intense vasoconstriction. Uric acid and uracil releases were increased by noradrenaline in a dose-dependent manner. However, the release of these substances did not fully correspond with the dose-dependent increase in O2 uptake and perfusion pressure, where changes in the latter occurred at lower doses of noradrenaline. Sciatic-nerve stimulation (skeletal-muscle contraction) did not increase the release of uracil, uric acid or uridine, but instead increased the release of inosine (7-fold) and hypoxanthine (2-fold). Since the UTP content as well as the UTP/ATP ratio are higher in smooth muscle than in skeletal muscle, it is proposed that release of uric acid and uracil arises from increased metabolism of the respective adenosine and uridine nucleotides during intense constriction of smooth muscle. PMID- 2327965 TI - High-efficiency transpeptidation catalysed by clostripain and electrostatic effects in substrate specificity. AB - Clostripain catalyses the transpeptidation between benzoylarginin ethyl ester and amino acid amides, oligopeptides, insulin A- and B-chains and tryptic peptides of myoglobin at millimolar substrate concentrations. The reactions proceed with temporary accumulation of the products, followed by hydrolytic decomposition. The yield was not affected significantly by the type of N-terminal amino acid, but was diminished markedly by the negative charges of the amine components. The yields for natural peptides were linearly related to the charge density of the peptides. PMID- 2327966 TI - Dietary-induced pre-translational control of rat fatty acid synthase. AB - We have examined the effects of starvation, normal lab chow and low-fat carbohydrate-rich diet on rat fatty acid synthase (FAS, EC 2.3.1.85). Under each of the dietary conditions the amount of FAS mRNA is different, the most being produced after a low-fat carbohydrate-rich diet. There is also an increase in the amount of FAS protein under the same conditions. To complete the picture we determined the incorporation of [14C]acetate into palmitate as a measure of enzyme activity. Data for cardiac and renal tissue also reflect a dietary influence on FAS. Therefore FAS mRNA, FAS protein and FAS activity are all responsive to dietary-induced signals, and our results suggest a pre translational regulation. PMID- 2327967 TI - Effect of hydroxycobalamin[c-lactam] on propionate and carnitine metabolism in the rat. AB - The administration in vivo of the cobalamin analogue hydroxycobalamin[c-lactam] inhibits hepatic L-methylmalonyl-CoA mutase activity. The current studies characterize in vivo and in vitro the hydroxycobalamin[c-lactam]-treated rat as a model of disordered propionate and methylmalonic acid metabolism. Treatment of rats with hydroxycobalamin[c-lactam] (2 micrograms/h by osmotic minipump) increased urinary methylmalonic acid excretion from 0.55 mumol/day to 390 mumol/day after 2 weeks. Hydroxycobalamin[c-lactam] treatment was associated with increased urinary propionylcarnitine excretion and increased short-chain acylcarnitine concentrations in plasma and liver. Hepatocytes isolated from cobalamin-analogue-treated rats metabolized propionate (1.0 mM) to CO2 and glucose at rates which were only 18% and 1% respectively of those observed in hepatocytes from control (saline-treated) rats. In contrast, rates of pyruvate and palmitate oxidation were higher than control in hepatocytes from the hydroxycobalamin[c-lactam]-treated rats. In hepatocytes from hydroxycobalamin[c lactam]-treated rats, propionylcarnitine was the dominant product generated from propionate when carnitine (10 mM) was present. The addition of carnitine thus resulted in a 4-fold increase in total propionate utilization under these conditions. Hepatocytes from hydroxycobalamin[c-lactam]-treated rats were more sensitive than control hepatocytes to inhibition of palmitate oxidation by propionate. This inhibition of palmitate oxidation was partially reversed by addition of carnitine. Thus hydroxycobalamin[c-lactam] treatment in vivo rapidly causes a severe defect in propionate metabolism. The consequences of this metabolic defect in vivo and in vitro are those predicted on the basis of propionyl-CoA and methylmalonyl-CoA accumulation. The cobalamin-analogue-treated rat provides a useful model for studying metabolism under conditions of a metabolic defect causing acyl-CoA accretion. PMID- 2327968 TI - Pseudoarginine: synthesis and properties of derivatives of delta-(1 imidazolyl)norvaline. AB - An analogue of arginine has been synthesized in which an imidazole ring occupies the position of the guanidino group of the natural amino acid. It was expected that peptides containing this amino acid when protonated might bind at enzymic sites specific for arginine, but that the pK of the imidazole ring, near 7, would facilitate entry of such peptides into cells, in contrast to peptides containing arginine. Other analogues of arginine can be visualized with a low side-chain pK, including isomers of the imidazole derivative which is the subject of this paper. These are viewed as 'pseudoarginines'. Our initial observations concern the properties of delta-(1-imidazolyl)norvaline in which a ring nitrogen atom is attached to norvaline, which thus becomes comparable to the guanidino delta nitrogen. Its synthesis is described along with several derivatives examined as substrates or inhibitors. Potential ligands containing delta-(1 imidazolyl)norvaline (ImNva) did not give evidence of interaction with trypsin or plasma kallikrein, serine proteinases which bind arginine derivatives. However, clostripain, a bacterial cysteine proteinase specific for arginine, was readily inactivated by Cbz-Phe-ImNva-CH2F and the rate of inactivation showed an acid pH dependence not observed, for example, in the inactivation of clostripain by Bz Phe-LysCH2F. PMID- 2327969 TI - Inhibition of polyamine oxidase in rats improves the sensitivity of urinary polyamines as markers for cell death. AB - In this study we investigated polyamine metabolism during inhibition of two polyamine-catabolizing enzymes. This was performed by treating rats with aminoguanidine [an inhibitor of Cu-dependent amine oxidase (CuAO)], NN'-bis(buta 2,3-dienyl)butane-1,4-diamine [MDL 72527, an inhibitor of FAD-dependent polyamine oxidase (PAO)], tetrachloromethane (hepatotoxic agent) and combinations of these compounds. Emphasis was laid on the origin and possible clinical usefulness of two polyamine metabolites: acetylisoputreanine-gamma-lactam and N1N12 diacetylspermine. Acetylisoputreanine-gamma-lactam is a normal constituent of human and rat urine. Treatment of rats with aminoguanidine led to undetectable urinary levels of acetylisoputreanine-gamma-lactam, whereas MDL 72527 treatment resulted in a 12-fold increase. Under normal conditions this compound represents a minor CuAO catabolite of N1-acetylspermidine, but may become of more importance under CuAO-induced conditions. N1N12-diacetylspermine was undetectable in urine samples from non-pregnant adults and rats, but became detectable after treating rats with MDL 72527. Additional tetrachloromethane poisoning resulted in a 35 fold increase of N1N12-diacetylspermine in urine and its appearance in liver. Hence urinary excretion of N1N12-diacetylspermine during PAO inhibition may serve as a sensitive marker for cell death. This was confirmed by myeloid-leukaemia bearing rats treated with MDL 72527, which also excreted N1N12-diacetylspermine in urine in relatively high amounts from at least day 14 until spontaneous death. PMID- 2327970 TI - The cysteine proteinases of the pineapple plant. AB - The pineapple plant (Ananas comosus) was shown to contain at least four distinct cysteine proteinases, which were purified by a procedure involving active-site directed affinity chromatography. The major proteinase present in extracts of plant stem was stem bromelain, whilst fruit bromelain was the major proteinase in the fruit. Two additional cysteine proteinases were detected only in the stem: these were ananain and a previously undescribed enzyme that we have called comosain. Stem bromelain, fruit bromelain and ananain were shown to be immunologically distinct. Enzymic characterization revealed differences in both substrate-specificities and inhibition profiles. A study of the cysteine proteinase derived from the related bromeliad Bromelia pinguin (pinguinain) indicated that in many respects it was similar to fruit bromelain, although it was found to be immunologically distinct. PMID- 2327971 TI - Purification and characterization of dichloromuconate cycloisomerase from Alcaligenes eutrophus JMP 134. AB - Dichloromuconate cycloisomerase from Alcaligenes eutrophus JMP 134 was purified to homogeneity. The enzyme has an Mr of about 270,000 as determined by gel filtration and consists of six to eight subunits of identical Mr 40,000 as determined by SDS/PAGE. Mn2+ ions as well as thiol groups are required for activity. A high Km value of about 4 mM for cis,cis-muconate explains the reported low activity with this compound. Relatively high Km values were also calculated for monochloro-substituted cis,cis-muconates (300-500 microM), in contrast with the low Km value of 20 microM for 2,4-dichloro-cis,cis-muconate. The catalytic constant of the pure enzyme was 3820 min-1 when measured with 2,4 dichloro-cis,cis-muconate. PMID- 2327972 TI - Kinetics and mechanism of DNA repair. Preparation, purification and some properties of caged dideoxynucleoside triphosphates. AB - Caged dideoxyribosylthymine triphosphate, dideoxyadenosine triphosphate and arabinosylcytosine triphosphate were prepared in high yield by reaction with 1-(2 nitrophenyl)diazoethane at pH 4 and room temperature for 24 h. Synthesis of caged alpha-32P-labelled dideoxyadenosine triphosphate (approx. 5000 Ci/mmol) in 85% yield was achieved by a modification of the method used for the synthesis of the unlabelled compounds. ATP was shown to be an excellent buffer in the synthesis of alpha-32P-labelled material, and in caged form to be an effective carrier in h.p.l.c. purification. Preparative h.p.l.c. was used to achieve purification of unlabelled caged compounds to greater than 98% purity and 32P-labelled material to 97% purity. Photolysis of unlabelled and 32P-labelled caged compounds by using XeF-excimer laser irradiation at 351 nm was characterized by using difference spectrophotometry and h.p.l.c. analysis. The stability of caged dideoxyadenosine [a-32P]triphosphate in the presence of cultured mammalian cells was evaluated; the adenosine derivative is essentially stable for 1 h. PMID- 2327973 TI - Kinetics and mechanism of DNA repair. Evaluation of caged compounds for use in studies of u.v.-induced DNA repair. AB - Experiments are described in which the feasibility of using caged dideoxy and other nucleoside triphosphate analogues for trapping breaks induced by u.v. radiation damage to mammalian cell DNA is evaluated. These nucleotide analogues that have a photolabile 1-(2-nitrophenyl)ethyl-protecting group attached to the gamma-phosphate are placed in situ by permeabilizing cells by exposure to hypo osmotic medium. The nucleoside triphosphate is released from the cage by a 351 nm u.v. laser pulse whence it may incorporate in the growing chain of DNA induced by the excision-repair process and terminate chain elongation. If the photoreleased dideoxynucleoside triphosphate is isotopically labelled in the alpha-phosphate position the break is trapped and labelled. Incorporation of radioactivity into trichloroacetic acid insoluble material in these experiments confirms their potential for use in studies of the kinetics of mammalian cell DNA repair. PMID- 2327974 TI - Differences between horse and human haemoglobins in effects of organic and inorganic anions on oxygen binding. AB - Despite the fact that the horse is one of the more common domesticated animals, there are few reports dealing with the properties of its blood, and no comprehensive study has been performed on the reactivity of horse haemoglobin towards organic and inorganic ions. Here we report data on the effects of the organic phosphates D-glycerate-2,3-bisphosphate (2,3-DPG) and InsP6, and of chloride on the properties of horse haemoglobin. Thus the effect of saturating concentrations of 2,3-DPG on the oxygen affinity of horse haemoglobin is about 60% lower than with human adult haemoglobin under the same experimental conditions. The same applies also to InsP6, whose effect on oxygen binding to horse haemoglobin is decreased by about 55% compared with human adult haemoglobin. On the whole, horse haemoglobin appears to be much less sensitive to organic phosphates than previously believed. These results are discussed in the light of the primary structure of the molecule. PMID- 2327975 TI - Exchange of fluorinated glucose across the red-cell membrane measured by 19F n.m.r. magnetization transfer. AB - The 19F n.m.r. spectrum of 3-fluoro-3-deoxy-D-glucose (3FG) in a red-cell suspension was observed to contain separate resonances from the intra- and extra cellular populations of both the alpha- and beta-anomers. This phenomenon was used with an n.m.r. spin-transfer procedure to measure the rate of exchange of the anomers across the human red-cell membrane under equilibrium-exchange conditions at 37 degrees C. The beta-anomer crossed the membrane significantly more quickly than the alpha-anomer. At a total 3FG concentration of 9.3 mM; the first-order rate constants for the efflux of the alpha- and beta-anomers were 0.41 +/- 0.15 and 0.88 +/- 0.20 s-1 respectively. The measurable 3FG exchange was inhibited by 75 and 100% respectively by the glucose-transport inhibitors cytochalasin B and phloretin. Glucose inhibited the exchange of 3FG, and the results were consistent with glucose and 3FG binding to the hexose-transport protein with similar affinity. PMID- 2327976 TI - Iron K-edge X-ray-absorption spectroscopy of the iron-vanadium cofactor of the vanadium nitrogenase from Azotobacter chroococcum. AB - Iron K-edge e.x.a.f.s. data for the iron-vanadium cofactor (FeVaco) from Azotobacter chroococcum vanadium nitrogenase reported here provide further evidence for the structural similarity between this and the iron-molybdenum nitrogenase cofactor (FeMoco) from Klebsiella pneumoniae molybdenum nitrogenase [Arber, Flood, Garner, Gormal, Hasnain & Smith (1988) Biochem. J. 252, 421-425]. The e.x.a.f.s. data are consistent with the vanadium being present in a V-Fe-S cluster, thus confirming that the N-methylformamide extract of the VFe protein component of A. chroococcum vanadium nitrogenase does indeed contain a polynuclear metal-sulphur cluster. Additionally, a long Fe-Fe distance is observed as 0.369 nm, demonstrating the presence of a long-range order in the cluster. PMID- 2327977 TI - Loss of alkalophily in cell-wall-component-defective mutants derived from alkalophilic Bacillus C-125. Isolation and partial characterization of the mutants. AB - The cells of alkalophilic Bacillus sp. C-125 are shaped by peptidoglycan and enclosed by two acidic polymers (teichuronic acid and teichuronopeptide), which bind to the peptidoglycan. Three kinds of mutant strains defective in these acidic polymers were isolated from the strain C-125. These mutants grow poorly at alkaline pH to extents related to the degree of defect in the polymers, suggesting that these acidic polymers are essential for growth in an alkaline environment. These polymers may diminish penetration of hydroxide ions. PMID- 2327978 TI - The human heat-shock protein family. Expression of a novel heat-inducible HSP70 (HSP70B') and isolation of its cDNA and genomic DNA. AB - The human heat-shock protein multigene family comprises several highly conserved proteins with structural and functional properties in common, but which vary in the extent of their inducibility in response to metabolic stress. We have isolated and characterized a novel human HSP70 cDNA, HSP70B' cDNA, and its corresponding gene sequence. HSP70B' cDNA hybrid-selected an mRNA encoding a more basic 70 kDa heat-shock protein that both the major stress-inducible HSP70 and constitutively expressed HSC70 heat-shock proteins, which in common with other heat-shock 70 kDa proteins bound ATP. The complete HSP70B' gene was sequenced and, like the major inducible HSP70 gene, is devoid of introns. The HSP70B' gene has 77% sequence similarity to the HSP70 gene and 70% similarity to HSC70 cDNA, with greatest sequence divergence towards the 3'-terminus. The HSP70B' gene represents a functional gene, as indicated by Northern-blot analysis with specific oligonucleotides, hybrid-selected translation with a specific 3' cDNA sequence and S1 nuclease protection experiments. In contrast with HSP70 mRNA, which is present at low concentrations in HeLa cells and readily induced by heat or CdCl2 treatment in both fibroblasts and HeLa cells, HSP70B' mRNA was induced only at higher temperature and showed no basal expression. The differences in patterns of induction may be due to the special features of the promoter region of the HSP70B' gene. PMID- 2327979 TI - Characterization of peptide fluxes into human erythrocytes. A proton-n.m.r. study. AB - A new protocol for measuring cellular uptake of dipeptides was developed in which the problem of peptide hydrolysis is obviated by introduction into the cell suspension of a membrane-permeant peptidase inhibitor. The uptake of unlabelled dipeptide is readily monitored so long as some analytical technique is available for measuring the intracellular peptide concentration; in this study we used n.m.r. spectroscopy. Using this protocol, we demonstrated that dipeptide uptake by human erythrocytes occurs by simple diffusion through the lipid bilayer and not via a high-capacity protein-mediated transport system. Substantiating evidence includes demonstration that: (a) the fluxes are slow compared with known protein-mediated transport processes in human erythrocytes; (b) the uptake is not stereospecific; (c) the uptake does not display saturation kinetics; (d) the fluxes are significantly enhanced by butanol; (e) a distinct correlation exists between the size-corrected permeability coefficients of the dipeptides and their calculated n-octanol/water partition coefficients. It is calculated that under normal physiological conditions the diffusive fluxes of circulating plasma peptides into human erythrocytes are too small for these cells to play a significant role in dipeptide catabolism. PMID- 2327980 TI - Structural comparisons of the native and reactive-centre-cleaved forms of alpha 1 antitrypsin by neutron- and X-ray-scattering in solution. AB - alpha 1-Antitrypsin is the best-characterized member of the serpin (serine proteinase inhibitor) superfamily. Its solution structure was studied by high flux neutron-scattering and synchrotron X-ray-scattering. Neutron data show that its absorption coefficient A1% 280,1cm is 5.4. The neutron radius of gyration RG at infinite contrast for native alpha 1-antitrypsin is 2.61 nm, characteristic of a moderately elongated structure, and its cross-sectional RG is 1.34 nm. The internal inhomogeneity of scattering densities within alpha 1-antitrypsin is high at 29 x 10(-5). The X-ray RG is 2.91 nm, in good agreement with the neutron RG of 2.82 nm in 1H2O. This RG is unchanged in reactive-centre-cleaved alpha 1 antitrypsin. These parameters are also unchanged at pH 8 in sodium/potassium phosphate buffers up to 0.6 M. The neutron and X-ray curves for native alpha 1 antitrypsin were compared with Debye simulation based on the crystal structure of reactive-centre-cleaved (papain) alpha 1-antitrypsin. After allowance for residues not visible in the crystallographic electron-density map, and rejoining the proteolysed site between Met-358 and Ser-359 by means of a relatively minor conformational re-arrangement, good agreement to a structural resolution of 4 nm is obtained with the neutron data in two contrasts and with the X-ray data. The structures of the native and cleaved forms of alpha 1-antitrypsin are thus similar within the resolution of solution scattering. This places an upper limit on the magnitude of the presumed conformational changes that occur in alpha 1 antitrypsin on reactive-centre cleavage, as indicated in earlier spectroscopic investigations of the Met-358-Ser-359 peptide-bond cleavage. Methods for scattering-curve simulations from crystal structures are critically assessed. The RG data lead to dimensions of 7.8 nm x 4.9 nm x 2.2 nm for native alpha 1 antitrypsin. The high internal inhomogeneity and the asymmetric shorter semi-axes of 4.9 nm and 2.2 nm suggest that the three oligosaccharide chains of alpha 1 antitrypsin are essentially freely extended into solvent in physiological conditions. This conclusion is also supported by the Debye simulations, and by modelling based on hydrodynamic parameters. PMID- 2327981 TI - 1H-n.m.r. studies of the isolated activation segment from pig procarboxypeptidase A. AB - The isolated activation segment (asA) from pig pancreatic procarboxypeptidase A was studied by 1H-n.m.r. spectroscopy over a wide range of solution conditions. Isolated asA shows many characteristics of compactly folded globular proteins, such as the observation of perturbed positions for resonances from methyl groups, alpha-carbon atoms, histidine residues and the tyrosine residue. The single tyrosine residue (Tyr-70) exhibits a very high pKa, and both histidine and tyrosine residues show slow chemical modification (deuteration and iodination). In contrast, asA shows rapid NH exchange. Analysis of the spectra by pH titration and nuclear Overhauser effects revealed several residue interactions. Quantitative analysis of deuterium and tritium exchange allowed the assignment of the histidine C-2-H resonances to their respective residues in the sequence. His 66, the closest to the sites of proteolytic attack in the proenzyme, is shown to be the most accessible to solvent in procarboxypeptidase A. It was also shown that asA is thermally very stable ['melting' temperature (Tm) 88 degrees C] and requires a high urea concentration for denaturation (6.25 M, at pH 7.5). Evidence is presented for some degree of conformational flexibility in the premelting range, a feature that could be ascribed to the preponderance of helical secondary structure and to the lack of disulphide bridges. The free solution structure of asA is probably unchanged when it binds to carboxypeptidase A. PMID- 2327982 TI - Differences in the cytochrome P-450 isoenzymes involved in the 2-hydroxylation of oestradiol and 17 alpha-ethinyloestradiol. Relative activities of rat and human liver enzymes. AB - The metabolism of oestradiol and 17 alpha-ethinyloestradiol to their 2-hydroxy derivatives is an important determinant in their biological effects. In this work, we have investigated which rat or human cytochrome P-450 isoenzymes are involved in catalysing these reactions. Oestradiol 2-hydroxylation was catalysed by a wide variety of rat cytochrome P-450s from gene families P450IA, P450IIB, P450IIC and P450IIIA. Interestingly, 17 alpha-ethinyloestradiol, which only differs structurally from oestradiol at a position distant from the site of oxidation, was metabolized predominantly by members of the P450IIC gene subfamily. In order to establish which enzymes are responsible for the oxidation of these substrates in man, antibodies to rat liver cytochrome P-450 isoenzymes were used to inhibit these reactions in a panel of human liver microsomal fractions. Also, possible correlations between the proteins recognized by the antibodies and the 2-hydroxylation rate were determined. These experiments provide evidence that 2-hydroxylation of 17 alpha-ethinyloestradiol in man is catalysed by cytochromes from the P450IIC, P450IIE and P450IIIA gene families. In contrast, the major proteins involved in oestradiol metabolism are from the P450IA gene family, although members of the P450IIC and P450IIE gene families may also play a role. These data demonstrate that the differences in the capacity of rat P-450s to metabolize these substrates are also present in the comparable enzymes involved in man, and that a variety of factors will determine the rate of disposition of these compounds in man. PMID- 2327983 TI - Affinity labelling of the folate-binding protein in pig intestine. AB - A specific transport system for folate and a high-affinity folate-binding protein have been identified in pig intestinal brush-border membranes. To determine if the binding protein plays a role in folic acid (PteGlu) uptake in to the cell, the inactivation of folate binding and transport by N-hydroxysuccinimide esters of folic acid (NHS-PteGlu) was compared. In addition, the number of brush-border proteins modified by the affinity reagent was assessed. Brush-border vesicles were incubated with various concentrations of NHS-PteGlu or NHS-methotrexate. Transport and binding of [3H]PteGlu by the vesicles were measured at 37 and 4 degrees C respectively by using the vacuum-filtration technique. NHS-methotrexate and NHS-PteGlu specifically inhibited PteGlu transport. Incubating the vesicles with 1 microM-NHS-PteGlu inactivated [3H]PteGlu transport by 60% and binding by 80%. Half-maximal inhibition of both transport and binding was observed at similar concentrations of the affinity reagent (0.05 and 0.07 microM-NHS-PteGlu respectively). Treating the vesicles with radiolabelled NHS-PteGlu followed by gel electrophoresis and autoradiography revealed a specifically labelled protein with an Mr of 56,000. These results indicate that the intestinal folate-binding and transport proteins are identical and that the function of the folate-binding protein is to transport folate into the cell. PMID- 2327984 TI - Isolation from fetal bovine serum of an apolipoprotein-H-like protein which inhibits thymidine incorporation in fetal calf erythroid cells. AB - A 46 kDa heparin-binding protein which inhibits thymidine incorporation in cultures of fetal calf liver erythroid cells was isolated from fetal bovine serum by affinity chromatography on heparin-Sepharose, ion-exchange chromatography, gel filtration and reversed-phase h.p.l.c. The N-terminal sequence of the first 22 amino acids showed 81% identity with the published sequence of human apolipoprotein H. The isolated protein inhibited thymidine incorporation with an ED50 (concn. producing 50% of maximal effect) of 36 nM. A 100% inhibition of thymidine incorporation and a 40% decrease in cell numbers in cultures of fetal calf erythroid cells were observed at a protein concentration of 840 nM. No effects could be seen in cultures of 3T3 cells used as controls. Human apolipoprotein H had no inhibitory activity in any of the cell cultures tested, suggesting a species-specificity or a different structure or function for the bovine heparin-binding protein. PMID- 2327985 TI - Acyl-CoA chain length affects the specificity of various carnitine palmitoyltransferases with respect to carnitine analogues. Possible application in the discrimination of different carnitine palmitoyltransferase activities. AB - The activities of carnitine palmitoyltransferases (CPTs) of mitochondrial outer and inner membranes and of peroxisomes have been studied with carnitine analogues, namely DL-thiolcarnitine, DL-sulphocarnitine and L-aminocarnitine, using palmitoyl-CoA or octanoyl-CoA as co-substrate. With sulphocarnitine, both of the mitochondrial CPTs and the malonyl-CoA-sensitive CPT of peroxisomes showed appreciable activity with palmitoyl-CoA, but relatively lower activity when octanoyl-CoA was the co-substrate. The soluble CPT of peroxisomes did not show any activity with sulphocarnitine in the presence of either acyl-CoA. With thiolcarnitine, all of the CPTs showed more activity with palmitoyl-CoA than with octanoyl-CoA. None of the CPTs showed any activity with aminocarnitine and palmitoyl-CoA, but when the acyl donor was octanoyl-CoA, both of the malonyl-CoA sensitive CPT enzymes showed considerable activity, unlike the malonyl-CoA insensitive CPT isoenzymes. Aminocarnitine inhibited palmitoylcarnitine formation by both of the mitochondrial CPTs and by the CPT of gradient-purified peroxisomes, but the purified peroxisomal soluble CPT was not inhibited. These results show that the interaction of CPT enzymes with carnitine analogues, as substrates or inhibitors, is influenced by the chain length of the acyl-CoA substrate, and that the use of the appropriate carnitine analogue and acyl-CoA is likely to be useful for the discrimination of the various CPT activities in CPT deficiency disorders. PMID- 2327986 TI - A point mutation in the cytoplasmic domain of the transferrin receptor inhibits endocytosis. AB - The rate of receptor-mediated endocytosis of diferric 125I-transferrin by Chinese hamster ovary cells expressing human transferrin receptors was compared with the rate measured for cells expressing hamster transferrin receptors. It was observed that the rate of endocytosis of the human transferrin receptor was significantly higher than that for the hamster receptor. In order to examine the molecular basis for the difference between the observed rates of endocytosis, a cDNA clone corresponding to the cytoplasmic domain of the hamster receptor was isolated. The predicted primary sequence of the cytoplasmic domain of the hamster transferrin receptor is identical with that of the human receptor, except at position 20, where a tyrosine residue in the human sequence is replaced with a cysteine residue. To test the hypothesis that this structural change in the receptor is related to the difference in the rate of internalization, we used site-directed mutagenesis to examine the effect of the replacement of tyrosine-20 with a cysteine residue in the human transferrin receptor. It was observed that the substitution of tyrosine-20 with cysteine caused a 60% inhibition of the rate of iron accumulation by cells incubated with [59Fe]diferric transferrin. No significant difference between the rate of internalization of the mutant (cysteine-20) human receptor and the hamster receptor was observed. Thus the substitution of tyrosine-20 with a cysteine residue can account for the difference between the rate of endocytosis of the human and hamster transferrin receptors. PMID- 2327987 TI - Purification and characterization of a new xylanase (xylanase B) produced by Streptomyces lividans 66. AB - A new extracellular xylanase produced by Streptomyces lividans 66 was isolated from a genetically engineered clone of that strain. This enzyme, named xylanase B, has an Mr of 31,000 and acts specifically on xylan as an endo-type xylanase producing short-chain xylo-oligosaccharides. The activity is optimal at pH 6.5 and at a temperature of 55 degrees C, which is similar to that of the previously characterized xylanase A. Xylanase B is glycosylated and has a pI of 8.4; its Km and Vmax. values are 3.71 mg/ml and 1.96 mmol/mg of enzyme respectively. Specific antibodies raised against xylanase A show no cross-reaction with xylanase B; however, the anti-(xylanase B) antibodies react slightly with xylanase A. A comparison of the hydrolysis products obtained from oat-spelts xylan with both enzymes show that xylanase A preferentially degrades short-chain oligo-xylosides, whereas xylanase B acts on the longer, water-insoluble, molecules. PMID- 2327988 TI - Kinetic analysis of duck epsilon-crystallin, a lens structural protein with lactate dehydrogenase activity. AB - Biochemical characterization and kinetic analysis of epsilon-crystallin from the lenses of common ducks were undertaken to elucidate the enzyme mechanism of this unique crystallin with lactate dehydrogenase (LDH) activity. Despite the structural similarities between epsilon-crystallin and chicken heart LDH, differences in charge and kinetic properties were revealed by isoenzyme electrophoresis and kinetic studies. Bi-substrate kinetic analysis examined by initial-velocity and product-inhibition studies suggested a compulsory ordered Bi Bi sequential mechanism with NADH as the leading substrate followed by pyruvate. The products were released in the order L-lactate and NAD+. The catalysed reaction is shown to have a higher rate in the formation of L-lactate and NAD+. Substrate inhibition was observed at high concentrations of pyruvate and L lactate for the forward and reverse reactions respectively. The substrate inhibition was presumably due to the formation of epsilon-crystallin-NAD(+) pyruvate or epsilon-crystallin-NADH-L-lactate abortive ternary complexes, as suggested by the product-inhibition studies. The significance and the interrelationship of duck epsilon-crystallin with other well-known LDHs are discussed with special regard to its role as a structural protein with some enzymic function in lens metabolism. PMID- 2327989 TI - Phosphate and calcium uptake by mitochondria and by perfused rat liver induced by the synergistic action of glucagon and vasopressin. AB - Co-administration of glucagon and vasopressin to rat liver perfused with buffer containing 1.3 mM-Ca2+ induces a 4-fold increase in Pi in the subsequently isolated mitochondria (from approx. 9 to approx. 40 nmol/mg of mitochondrial protein). This increase is not attributable to PPi hydrolysis, and is not observed if the perfusate Ca2+ is lowered from 1.3 mM to 50 microM. The increase in mitochondrial Pi closely parallels that of mitochondrial Ca2+; when the increase in Pi and Ca2+ accumulation is maximal, the molar ratio is close to that in Ca3(PO4)2. Measurement of changes in the perfusate Pi revealed that, whereas administration of glucagon or vasopressin alone brought about a rapid decline in perfusate Pi, the largest decrease (reflecting net retention of Pi by the liver) was observed when the hormone was co-administered in the presence of 1.3 mM-Ca2+. The synergistic action of glucagon plus vasopressin was nullified by lowering the perfusate Ca2+ to 50 microM. The data provide evidence that, whereas glucagon may be able to alter Pi fluxes directly in intact liver, any alterations induced by vasopressin are indirect and result only from its action of mobilizing Ca2+. PMID- 2327990 TI - Differential interactions of human kallikrein-binding protein and alpha 1 antitrypsin with human tissue kallikrein. AB - The characteristics of a new kallikrein-binding protein in human serum and its activities were studied. Both the kallikrein-binding protein and alpha 1 antitrypsin form 92 kDa SDS-stable and heat-stable complexes with human tissue kallikrein. In non-SDS/PAGE, the mobility of these complexes differ. Complex formation between kallikrein and the binding protein is inhibited by heparin, whereas that between kallikrein and alpha 1-antitrypsin is heparin-resistant. In normal or alpha 1-antitrypsin-deficient-serum, the amount of 92 kDa SDS-stable complex formed upon addition of kallikrein is not related to serum alpha 1 antitrypsin levels. The rate of complex-formation between kallikrein and the binding protein is 12 times higher than that between kallikrein and alpha 1 antitrypsin. Purified alpha 1-antitrypsin, which exhibits normal elastase binding, has a kallikrein-binding activity less than 5% of that of serum. Binding of tissue kallikrein in serum is not inhibited by increasing elastase concentrations, and elastase binding in serum is not inhibited by excess tissue kallikrein. A specific monoclonal antibody to human alpha 1-antitrypsin does not bind to either 92 kDa endogenous or exogenous kallikrein complexes isolated from human serum. The studies demonstrate a new tissue kallikrein-binding protein, distinct from alpha 1-antitrypsin, is present in human serum. PMID- 2327991 TI - Re-evaluation of the interaction of malonyl-CoA with the rat liver mitochondrial carnitine palmitoyltransferase system by using purified outer membranes. AB - 1. The interaction of malonyl-CoA with the outer carnitine palmitoyltransferase (CPT) system of rat liver mitochondria was re-evaluated by using preparations of highly purified outer membranes, in the light of observations that other subcellular structures that normally contaminate crude mitochondrial preparations also contain malonyl-CoA-sensitive CPT activity. 2. In outer-membrane preparations, which were purified about 200-fold with respect to the inner membrane-matrix fraction, malonyl-CoA binding was largely accounted for by a single high-affinity component (KD = 0.03 microM), in contrast with the dual site (low- and high-affinity) previously found with intact mitochondria. 3. There was no evidence that the decreased sensitivity of CPT to malonyl-CoA inhibition observed in outer membranes obtained from 48 h-starved rats (compared with those from fed animals) was due to a decreased ratio of malonyl-CoA binding to CPT catalytic moieties. Thus CPT specific activity and maximal high-affinity [14C]malonyl-CoA binding (expressed per mg of protein) were increased 2.2- and 2.0-fold respectively in outer membranes from 48 h-starved rats. 4. Palmitoyl-CoA at a concentration that was saturating for CPT activity (5 microM) decreased the affinity of malonyl-CoA binding by an order of magnitude, but did not alter the maximal binding of [14C]malonyl-CoA. 5. Preincubation of membranes with either tetradecylglycidyl-CoA or 2-bromopalmitoyl-CoA plus carnitine resulted in marked (greater than 80%) inhibition of high-affinity binding, concurrently with greater than 95% inhibition of CPT activity. These treatments also unmasked an effect of subsequent treatment with palmitoyl-CoA to increase low-affinity [14C]malonyl-CoA binding. 6. These data are discussed in relation to the possible mechanism of interaction between the malonyl-CoA-binding site and the active site of the enzyme. PMID- 2327992 TI - Divalent cation-dependent structure in the platelet membrane glycoprotein Ia-IIa (VLA-2) complex. AB - Recent studies have shown that the platelet membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mg(++)-dependent adhesion of platelets to collagen and that this adhesion is inhibited by Ca++ in a simple, linear, noncompetitive manner. These findings suggested that separate binding sites for Mg++ and Ca++ stabilize different divalent cation-dependent structures within the receptor complex. To provide evidence for the existence of such structures purified platelet Ia-IIa complex was subjected to limited proteolytic digestion in the presence of Mg++, Ca++, Mg++ and Ca++, or EDTA and the resulting peptides mapped by SDS-PAGE using both one and two-dimensional techniques. Unique patterns of tryptic peptides were produced under each of the conditions. The results indicate that Mg++ and Ca++ stabilize different structures within the Ia-IIa (VLA-2) complex and that these structures influence both the collagen binding activity and proteolytic susceptibility of the complex. PMID- 2327993 TI - rho gene amplification and malignant transformation. PMID- 2327994 TI - Transcription of HIV1 is inhibited by DNA methylation. AB - A possible role of DNA methylation as a factor in HIV latency was studied by methylating a HIV1-LTR-CAT plasmid in vitro and measuring its expression after transfection on Vero cells. Methylation with a eukaryotic DNA methylase resulted in a 70% inhibition of chloramphenicol acetyltransferase expression, in the absence as well as in the presence of the HIV1 trans-activator protein TAT in the cell. A similar degree of transcription inhibition was obtained by methylation of the only Hpa II site at position-143 in the HIV1-LTR with the bacterial Hpa II methylase. In contrast to the effect by eukaryotic methylation, the inhibition by Hpa II methylation could be partially reversed by cotransfection of the TAT gene. The reason may lie in an about 40% demethylation at the Hpa II site which was concomitantly observed. PMID- 2327995 TI - zeta-Related protein kinase C in nuclei of nerve cells. AB - To determine whether or not PKC is present in the nuclei of nerve tissue we made use of biochemical and immunocytochemical techniques. A 219-fold purification of rabbit brain nuclear protein kinase C was achieved by sequential steps of Triton X-100 extraction of isolated nuclei, DEAE-cellulose, Butyl-toyopearl and hydroxylapatite chromatography. The major peak of protein kinase C activity was eluted from the hydroxylapatite column at the KPO4 concentration of 0.3 M. Both Ca2+ and Ptd Ser were required for stimulation of the enzyme. Immunoblot analysis revealed that the kinase fraction was immunoreactive with a polyclonal antibody, PC-zeta, that had been raised against a peptide synthesized according to the deduced sequence of rat zeta protein kinase C. Light-microscopy revealed strong immunoreactivity in the nuclei of Purkinje cells in cerebellum and pyramidal cells in the rat cerebral cortex. These observations suggest that a zeta-related protein kinase C is present in the nuclei of nerve cells. PMID- 2327996 TI - Mechanism of synergistic induction of hepatic heme oxygenase by glutethimide and iron: studies in cultured chick embryo liver cells. AB - Heme oxygenase, the rate controlling enzyme for heme catabolism, is inducible by a variety of treatments, some of which induce by a heme-dependent mechanism and others by a heme-independent mechanism. This work shows that, in cultured chick embryo liver cells, synergistic induction of heme oxygenase by iron, added with the phenobarbital-like drug, glutethimide was heme-dependent. Addition of an inhibitor of heme biosynthesis abolished the synergistic induction of heme oxygenase providing evidence for the heme-dependent mechanism of induction. Glutethimide and iron appeared to induce at the transcriptional level since both heme oxygenase mRNA and protein levels correlate with changes in heme oxygenase activity. PMID- 2327998 TI - Maternal transmission of mitochondrial DNA in ducks. AB - Maternal transmission of mitochondrial DNA (mtDNA) has been studied in amphibians, insects and mammals, but little is known about mtDNA inheritance in the ovaripirous avian species. In this study, we have constructed the physical maps of mitochondrial genomes from two different genera of ducks (Cairina and Anas) and taken advantage of the availability of their hybrids to demonstrate that mtDNA is maternally inherited. PMID- 2327997 TI - Complete homology in metallothionein from two genera of ducks and their hybrids. AB - Metallothionein purified from two genera of domesticated duck, Anas platyrhnchos and Cairina muschata, and their hybrid were analyzed and shown to consist of one identical amino acid sequence. Since most vertebrates carry two or more isospecies of this inducible, thiol rich, metal sequestering protein, this finding suggests that duck metallothionein is evolutionary primitive. PMID- 2327999 TI - Inhibition of human immunodeficiency virus type 1 replication and cytopathicity by synthetic soluble catecholamine melanins in vitro. AB - Synthetic soluble melanins were synthesized by spontaneous oxidation of L dopamine, norepinephrine or 5-hydroxytryptamine (serotonin) in weak alkaline solution. These three melanins inhibited infection of human CD4+ lymphoblastoid cells (MT-2) by cell-free human immunodeficiency virus type 1 (HIV-1), without cell toxicity, at concentrations of 0.15-10 micrograms/ml. Also, syncytium formation and resulting cytopathic effects when uninfected cells were mixed with chronic HIV-1-infected cells were blocked by these melanins. Antisyncytial activity was greater when infected cells were preincubated with melanin than when uninfected cells were preincubated with melanin, thus suggesting that interaction of melanin with viral proteins is an important aspect of the antiviral mechanism. These results make synthetic soluble melanins interesting candidates for further study as possible anti-HIV-1 therapeutics. PMID- 2328000 TI - In vitro hydroxylation of bentazon by microsomes from naphthalic anhydride treated corn shoots. AB - In vitro metabolism of the herbicide bentazon was studied in microsomal membranes isolated from 6-day-old etiolated corn shoots. Microsomes isolated from shoots of nontreated seeds did not metabolize bentazon when assayed with NADPH or peroxides. However, microsomes isolated from shoots of seeds pretreated with naphthalic anhydride formed a single bentazon metabolite when provided with NADPH. The metabolite was identified as 6-hydroxybentazon, the major phase I metabolite produced in vivo. In vitro formation of this metabolite was strongly inhibited by carbon monoxide, nitrogen, and tetcyclacis (10 microM). The results suggest that aryl hydroxylation of bentazon in corn shoots is catalyzed by a cytochrome P-450 (E.C. 1.14.14.1) and that a seed pretreatment with naphthalic anhydride is necessary for recovery of activity in vitro. PMID- 2328001 TI - Identification of a new carcinoembryonic antigen (CEA) family member in human fetal liver--cloning and sequence determination of pregnancy-specific glycoprotein 7. AB - The carcinoembryonic antigen gene family consists of the CEA- and the Pregnancy Specific Glycoprotein- (PSG) subfamilies. Human fetal liver express several PSGs. Here we report cloning and sequencing of a new PSG subfamily member, PSG7. It is the fifth type of PSG found in fetal liver. PSG7 has the N-A1-A2-B2-C domain arrangement. Unlike other PSGs the N-terminal of PSG7 is unblocked. PSG7 has a cysteine in the C-terminal domain, which may allow dimerization. Variability analysis according to Wu and Kabat reveals that the region in the N-domain corresponding to complementarity determining region 3 of immunoglobulin is different between PSG subfamily members. Many members, including PSG7, contain the RGD sequence in this region. The CD2 region as well as two other short sequences (in N and A1 domains respectively) also show some variability. The function of PSGs is probably linked to the N-domain and the CDR2- and CD3-like regions are most likely responsible for ligand binding. PMID- 2328002 TI - Deficient lysosomal carboxypeptidase activity in galactosialidosis. AB - In the lysosome, the glycosidases neuraminidase (EC 3.2.1.18) and beta galactosidase (EC 3.2.1.23) are associated to a 52 kDa "protective protein" to form a large multi-enzymatic complex. Deficient synthesis or inactivation of this protective protein causes galactosialidosis, a lysosomal storage disorder in man in which both neuraminidase and beta-galactosidase activities are deficient. Since the protective protein possesses extensive sequence homology with carboxypeptidase Y (carb Y) and the KEX 1 gene product from yeast, we have used the artificial substrate N-CBZ-Phe-Leu to detect and characterize the peptidase activity of the lysosomal carboxypeptidase (carb L). Using both a purified preparation of the lysosomal multi-enzymatic complex and cultured skin fibroblasts of patients affected with galactosialidosis, we demonstrate that the 52 kDa protective protein is responsible for carb L activity. The fibroblasts of three patients affected with late infantile and juvenile galactosialidosis were found to be deficient in carb L activity (1.4% of normal mean value). PMID- 2328003 TI - Basic fibroblast growth factor inhibits delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity in cultured immature Leydig cells. AB - Basic fibroblast growth factor inhibited basal delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity in cultured Leydig cells from immature rats in a concentration- and time-dependent manner. Maximal inhibition was achieved with 5 10 ng/ml basic fibroblast growth factor following approximately 48 h of exposure. The inhibition of basal delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity was not altered by human chorionic gonadotropin; however, cycloheximide (0.5-2.0 micrograms/ml) partially reversed the effects of basic fibroblast growth factor in a dose-dependent manner. These studies suggest that locally-produced basic fibroblast growth factor may modulate Leydig cell testosterone formation by regulating delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity. PMID- 2328004 TI - A DNA-binding homeodomain in histone H1. AB - The structure of the globular domain of chicken histone H1 was compared here with that of the DNA-binding homeodomain in the Drosophila Antp protein, and they were observed to display considerable similarity. Both of them consist of three or four alpha-helices separated by well-defined turns. Charged residues in the aminoterminal end of alpha 3 are therefore suggested to be responsible for sequence-specific recognition of DNA by the histone. In addition, alpha 2 of H1, with a short leucine zipper in it, may be capable of protein-protein interaction in a similar manner to the other homeodomains. PMID- 2328005 TI - Separation of the cytochromes P-450 in pig kidney mitochondria catalyzing 1 alpha , 24- and 26-hydroxylations of 25-hydroxyvitamin D3. AB - The cytochromes P-450 in pig kidney mitochondria catalyzing 1 alpha-, 24- and 26 hydroxylations of 25-hydroxyvitamin D3 have been separated. The cytochrome P-450 fractions required NADPH, mitochondrial ferredoxin and ferredoxin reductase for catalytic activity. The present report demonstrates that different forms of cytochrome P-450 are involved in 1 alpha-, 24- and 26-hydroxylations of 25 hydroxyvitamin D3 and provides a basis for further purification and characterization of these enzymes. PMID- 2328006 TI - Striated scallop muscle relaxation: fast force transients produced by photolysis of Diazo-2. AB - Relaxation of the myosin regulated striated adductor muscles of Pecten maximus was initiated by the photolysis of the caged Ca2+ chelator, Diazo-2. The fibres relaxed to approximately 30% of the maximum tension with a mean half-time of 17.9 +/- 1.6 ms (n = 7, temp 12 degrees C), much faster than the rates observed in intact muscle at the same temperature. This indicates that in the intact adductor muscle the slower relaxation rate is determined by the speed of Ca2+ removal from the sarcoplasm. The faster rate of relaxation of scallop muscle in vitro, compared with frog skeletal muscle may reflect different mechanisms of regulation of the crossbridge cycle. PMID- 2328007 TI - Lysophosphatidylcholine: essential role in the inhibition of endothelium dependent vasorelaxation by oxidized low density lipoprotein. AB - Endothelial cells are known to play an important role in the regulation of vascular tone. Here we demonstrate that modified low density lipoprotein (LDL) with copper oxidation or phospholipase A2 treatment elicits a potent inhibitory action on endothelium-dependent relaxations evoked by acetylcholine, although native LDL does not affect endothelium-dependent relaxations. Phosphatidylcholine of native LDL is converted to lysophosphatidylcholine during these modifications. Furthermore, lysophosphatidylcholine fraction separated from oxidized LDL (0.5mg.protein/ml) by thin layer chromatography abolished endothelium-dependent relaxations, although the remaining lipid fraction had little effects on endothelium-dependent relaxations. These results indicate that lysophosphatidylcholine is the principal substance for the impairment of endothelium-dependent relaxations by oxidized LDL and phospholipase A2 treated LDL. PMID- 2328008 TI - Phosphatidic acid and not diacylglycerol generated by phospholipase D is functionally linked to the activation of the NADPH oxidase by FMLP in human neutrophils. AB - It is widely accepted that the activation of the NADPH oxidase of phagocytes is linked to the stimulation of protein kinase C by diacylglycerol formed by hydrolysis of phospholipids. The main source would be choline containing phospholipid via phospholipase D and phosphatidate phosphohydrolase. This paper presents a condition where the activation of the respiratory burst by FMLP correlates with the formation of phosphatidic acid, via phospholipase D, and not with that of diacylglycerol. In fact: 1) in neutrophils treated with propranolol, an inhibitor of phosphatidate phosphohydrolase, FMLP plus cytochalasin B induces a respiratory burst associated with a stimulation of phospholipase D, formation of phosphatidic acid and complete inhibition of that of diacylglycerol. 2) The respiratory burst by FMLP plus cytochalasin B lasts a few minutes and may be restimulated by propranolol which induces an accumulation of phosphatidic acid. 3) In neutrophils stimulated by FMLP in the absence of cytochalasin B propranolol causes an accumulation of phosphatidic acid and a marked enhancement of the respiratory burst without formation of diacylglycerol. 4) The inhibition of the formation of phosphatidic acid via phospholipase D by butanol inhibits the respiratory burst by FMLP. PMID- 2328009 TI - Developmental and growth-related regulation of expression of serine dehydratase mRNA in rat liver. AB - In rat liver, serine dehydratase mRNA is undetectable in the late prenatal period, but its level increases rapidly after birth to a transient peak, and then after decrease gradually increases again to a maximum 2 weeks after birth that is slightly higher than that of adult liver. To determine whether mature quiescent hepatocytes proliferate without loss of differentiated functions, we measured the serine dehydratase mRNA contents in regenerating liver and primary cultured hepatocytes from adult rats. Partial hepatectomy resulted in a dramatic decrease in the mRNA content within 24 h and then its recovery within a week. In subconfluent cultures of adult rat hepatocytes that did not grow even in the presence of mitogens, serine dehydratase mRNA was maintained at a high level. However, when the hepatocytes were cultured at low cell density without added mitogens, their serine dehydratase mRNA content decreases to a quarter of that of subconfluent cultures. The possibility that the expression of serine dehydratase mRNA is regulated in G0/G1 transition before entry into the S phase and the relationship of the mRNA with growth are discussed. PMID- 2328010 TI - Expression pattern of acidic and basic fibroblast growth factor genes in adult rat eyes. AB - Although the retinal angiogenic and mitogenic factors have been identified to be acidic and basic fibroblast growth factors (aFGF and bFGF), little information has so far been available about the cells producing them and their function in retinal tissues. We found, by in situ hybridization, that the expression pattern of the aFGF gene differed remarkably from that of the bFGF gene in adult rat eyes. Our results demonstrated that the aFGF gene was produced by photoreceptor visual cells, neuronal cells in the inner nuclear layer and ganglion cells of the retina, in addition to pigment epithelial cells of the choroid, iris and ciliary body, and epithelial cells of the cornea, conjunctiva and lens, while bFGF was synthesized solely by the photoreceptor visual cells. PMID- 2328011 TI - Inositol 1,4,5-trisphosphate affinity chromatography. AB - Inositol 1,4,5-trisphosphate (IP3) affinity columns were made by coupling IP3 analogs to a supporting matrix. Sepharose 4B. IP3 5-phosphatase activity. IP3 3 kinase activity and IP3 binding activity from rat brain were absorbed on the IP3 columns. and were eluted by increasing KC1 concentration. This purification procedure increased the specific activities of these parameters 5-200-fold. Thus Sepharose 4B immobilized IP3 analogs can specifically interact with IP3-binding proteins, demonstrating that IP3 affinity columns are a good method for purifying such proteins. Furthermore, our results suggest that IP3 analogs can be linked to other molecules to make useful derivatives without loss of their biological activities. PMID- 2328012 TI - A new antileishmanial compound, phaseolinone. AB - Inclusion of phaseolinone, a newly described mycotoxin, at 20 micrograms per ml in a solid culture medium (blood agar overlay) and at 50 micrograms per ml in a liquid culture (medium 199) inhibited the growth of L. donovani promastigotes. About 90% of the motile promastigotes lost motility after exposure to 50 micrograms per ml of phaseolinone for 6-7 h and here 3-day-old culture was more sensitive than 7-day-old culture. In an in vitro assay, DNA dependent RNA polymerase activity of 3-day-old promastigotes was considerably inhibited in the presence of this toxin. Therefore, this key enzyme was suggested to be one of the sites of action of phaseolinone. PMID- 2328013 TI - Phaseolinone, a new mycotoxin, inhibits RNA polymerase(s) other than RNA polymerase II. PMID- 2328015 TI - Characterization of DNA pattern in the site of permanent attachment to the nuclear matrix located in the vicinity of replication origin. AB - The permanent sites of DNA attachment to the nuclear matrix in the domain of chicken alpha-globin genes originally found in erythrocyte nuclei have also been shown to exist in sperm and cultured fibroblast cells. A primary structure of a 1.7 kb fragment located in 5'-upstream region of chicken alpha-globin gene domain and containing both replication origin and permanent nuclear matrix attachment site has been determined. It was found to possess homologies with papovaviral replication origins and contain short internal repeats and GC-rich motifs. PMID- 2328014 TI - Expression of actin and myosin heavy chain genes in skeletal, cardiac and uterine muscles of young and old rats. AB - The steady-state levels of mRNA and transcription of alpha-skeletal actin (alpha SKA) and adult myosin heavy chain (MHC) genes were measured in the skeletal, cardiac and uterine muscles of young (22-25 week) and old (123-135 week) female rats. The effects of 10(-8) M 17 beta-estradiol/dexamethasone/T3 alpha on their transcription were also studied. The data show that the alpha-SKA mRNA level is lower in the old skeletal muscle and uterus, but is higher in the old myocardium. The adult MHC mRNA level is not different in the three muscles of both the ages. The transcription of alpha-SKA gene is lower in the skeletal muscle and higher in the uterus of old rats. It is unaltered in the myocardium of old rats. The transcription of adult MHC gene is lower in the old uterus. The effects of hormones on transcription of both the genes are different in the three muscles. We show that the expression of alpha-SKA gene is tissue-specific and age-related. The over-expression of alpha-SKA gene in the old myocardium is possibly due to derepression of the gene caused by hypertrophy of cardiac myocytes, and continuous hemodynamic pressure overload on the old heart. PMID- 2328016 TI - Biosynthesis of glycoconjugates in mitochondrial outer membranes. Preliminary characterization of the oligosaccharide moiety of a N-glycoprotein. AB - Outer mitochondrial membranes synthesize a N-glycoprotein by a direct incorporation of sugars from their nucleotide-donors into an endogenous protein acceptor. To characterize the oligosaccharide moiety of this N-glycoprotein, we sequentially incorporated [14C]-sugars into the protein acceptor. After pronase digest, the released [14C]-glycopeptides were fractionated on a QAE-Sephadex column which gave rise to 9% of neutral glycopeptides and 91% of charged glycopeptides. These latter were identified as bearing phosphate residues in the form of monoester (28%) and acid-stable diester (63%). The oligosaccharide moiety of this mitochondrial glycoprotein has been characterized as incomplete biantennary complex-type chains. PMID- 2328017 TI - The action of low density lipoprotein on vascular smooth muscle cells involves increase in intracellular pH. AB - The effect of low density lipoprotein (LDL) on the intracellular pH (pHi) of vascular smooth muscle cells (VSMC) was investigated using a fluorescent pH indicator, 2',7'-bis(carboxyethyl)carboxyfluorescein (BCECF). LDL and apoprotein B (apo-B), a binding protein for the LDL receptor, caused transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of Na+/H+ exchanger. NH4Cl also caused intracellular alkalization, but independently of extracellular Na+. LDL, apo-B and NH4Cl all stimulated thymidine incorporation. These results indicate that the binding of LDL to its receptor stimulates Na+/H+ exchanger, resulting in alkalization of VSMC and suggest that this may function as a massage in stimulation of DNA synthesis evoked by LDL. PMID- 2328018 TI - Role of extracellular calcium in the metabolic and hemodynamic actions of sympathetic nerve stimulation, noradrenaline and prostaglandin F2 alpha in perfused rat liver. Differential inhibition by nifedipine and verapamil. AB - In perfused rat liver hepatic nerve stimulation (10 Hz, 2 ms) caused an increase in glucose and lactate output, a decrease in flow and an overflow of noradrenaline into the hepatic vein. Noradrenaline (1 microM) (NA) and prostaglandin F2 alpha (5 microM) (PGF2 alpha), which are implicated as mediators of nerve action, elicited similar effects. 1) All actions of nerve stimulation and the hemodynamic but not the metabolic effects of noradrenaline and PGF2 alpha were largely dependent on extracellular calcium. 2) The dihydropyridine type calcium antagonist nifedipine (5 microM) inhibited the hemodynamic but not the metabolic actions of nerve stimulation, NA and PGF2 alpha, while the phenylalkylamine type calcium antagonist verapamil (5 microM) had no effect. These findings allow the following conclusions: Calcium influx into I nerve endings, necessary for the release of neurotransmitter, II parenchymal cells, for the display of metabolic effects induced by nerve stimulation, and III the actions of NA and PGF2 alpha, do not appear to be mediated by the normal affinity nifedipine- or the verapamil-sensitive channels. Calcium influx into vascular smooth muscle and/or endothelial cells for the display of hemodynamic action induced by nerve stimulation and the NA and PGF2 alpha effects, appear to occur through nifedipine-sensitive but verapamil-insensitive channels. PMID- 2328019 TI - Modulation of EGF-receptors by phorbol ester in small intestinal crypt cells. AB - We have previously shown that EGF promotes growth and proliferation of enterocytes isolated from the crypts of the rat small intestine (IEC-6). In the present studies we have measured the affinity of EGF for its receptor, and estimated the number of surface EGF receptors on IEC-6 cells. Scatchard analysis indicates IEC-6 cells display 45,000 EGF receptors per cell with a dissociation constant of 41 pM. Treatment with phorbol-12-myristate-13-acetate (PMA) results in a dose-dependent inhibition of cell growth which is paralleled by reduced binding of 125I-EGF. Incubation of IEC-6 cells with 10 nM PMA results in a 70 percent decrease in the number of EGF receptors without a significant change of receptor affinity (kd 68 pM vs 41 pM). PMA treatment is also associated with a significant increase of protein kinase-C activity in IEC-6 cells. The reciprocal relationship between protein kinase-C activation and EGF receptors suggests in this cell line of crypt enterocytes, protein kinase-C may inhibit cellular proliferation by modulating EGF receptors. PMID- 2328020 TI - Diacetylputrescine and its analog suppress c-myc expression and activation of human B-lymphocytes. AB - Our studies demonstrate that diacetylputrescine (TMBA), and its analog hexamethylenebisacetamide, HMBA, inhibit the expression of the c-myc oncogene in activated human B-lymphocytes. Activation of human B-cells induced by anti-IgM is associated with the induction of c-myc by greater than 20 times basal levels, maximal levels occurring at about 2 hours. This increased c-myc expression is inhibited by greater than 90% by 3 mM TMBA or 3mM HMBA. TMBA and HMBA also inhibit by greater than 90% the subsequent activation of the B-cells. These diacetylated polyamines may play a regulatory role in B-cell activation. PMID- 2328021 TI - Factors affecting L-malate activation of mitochondrial malate dehydrogenase from chicken liver. AB - Mitochondrial malate dehydrogenase is activated by high concentrations of L malate. In this paper, several factors affecting this activation on chicken liver enzyme have been investigated. The results obtained show clearly that this phenomenon is an intrinsic property of this enzyme since it does not depend on pH or ionic strength of the reaction medium. However, L-malate activation decreases when NAD+ concentration diminishes (5mM----0.2 mM) in such a way that when NAD+ concentration is 0.2 mM, L-malate does not activate mitochondrial malate dehydrogenase. On the other hand, several activators of this enzymatic system, such as citrate or phosphate, also produce the elimination of this activation by L-malate; in this case, the phenomenon seems be due to a competitive binding to a regulatory site of the different metabolites implied. PMID- 2328022 TI - Linoleate and linolenate desaturation by rat hepatoma cells. AB - Morris 7777 rat hepatoma cells in culture possess high delta 6 and delta 5 desaturase activities over linolenic acid added to the medium as albumin or alpha fetoprotein complexes. After 2 hours incubation with [1-14C] linolenic acid (7 microM), around 40% of the radioactivity was recovered in other polyene fatty acids, mainly pentaenes. After 24 hours incubation with this substrate the polyene derivatives raised to more than 60%. However, [1-14C] linoleic acid was poorly converted to other polyene fatty acids. Linoleic acid up to 58 microM concentration in the medium do not inhibited linolenic acid desaturation. Long term supplementation with 50 microM linoleic or linolenic acid, which modified the fatty acid profile of hepatoma lipids, enhanced the desaturase activities against linoleic acid. Desaturase activities were not affected by the fatty acid protein carrier, alpha-fetoprotein or albumin. PMID- 2328023 TI - A hydrophobicity on skeletal muscle actin molecule modulated by nucleotide binding at a second site. AB - A hydrophobic region was detected on skeletal muscle actin molecule by change of fluorescence of a hydrophobic probe, 8-anilino-1-naphthalene-sulfonate (ANS). In previous papers (Hozumi, T. (1988) Biochem. Int. 17, 171-178; Hozumi, T. (1988) J. Biochem. (Tokyo) 104, 285-288) evidences for a second nucleotide binding site on a actin molecule were reported and it was shown that nucleotide interaction at the site induces conformational changes in actin molecule. The character of non polar region of actin molecule was altered by the binding of nucleotide at a new site of actin molecule, the fluorescence of the ANS-actin being greatly decreased, and its emission maximum undergoing a red-shift. These results show that nucleotide binding at a second site on actin changes its conformation, and the conformational change induces changes in the native surface hydrophobicity on actin molecule. PMID- 2328024 TI - Isolation of glyoxalase II from bovine liver mitochondria. AB - Bovine liver mitochondria contain about 10% of the total glyoxalase II activity in the homogenate. Electrophoresis and isoelectric focussing of either crude mitochondrial extract or the purified mitochondrial glyoxalase II resolved the enzyme activity into five forms (pl 6.3, 6.7, 7.1, 7.7, and 7.9). Since bovine liver cytosol contains a single form of glyoxalase II (pl 7.5), at least four forms are exclusively mitochondrial with no counterpart in the cytosol. The relative molecular mass of mitochondrial glyoxalase II is about 23-24 kDa, similar to the cytosolic form. The kinetic constants obtained using S-D-lactoyl, S-acetyl-, S-acetoacetyl-, and S-succinyl-glutathione as substrates are similar to those reported for glyoxalase II from rat liver mitochondria. S-D-Lactoyl- and S-acetoacetyl-glutathione are the best substrates. S-Acetylglutathione is the poorest substrate with respect to both Vmax and Km values. PMID- 2328025 TI - Relationship between L-tryptophan uptake and L-tryptophan 2,3-dioxygenase activity in rat hepatocytes. AB - The relationship between L-tryptophan uptake and tryptophan 2,3-dioxygenase activity in hepatocytes was examined and compared with the change of hepatic L leucine, L-phenylalanine, and L-tyrosine uptakes using isolated hepatocytes of rats in which the oxygenase was induced with L-tryptophan or hydrocortisone. In L tryptophan- or hydrocortisone-treated rat hepatocytes, the rate of L-tryptophan uptake into hepatocytes via the saturable high-affinity transport component significantly increased but the hepatic uptake rate of L-leucine did not change at all. In hydrocortisone-treated rat hepatocytes, a little stimulated hepatic uptake of L-phenylalanine or L-tyrosine was observed. In the stimulated hepatic uptake of L-tryptophan via the high-affinity transport component, the Km value did not change but the Vmax value increased. Liver plasma membranes prepared from rats treated with L-tryptophan or hydrocortisone showed the same binding rate of L-tryptophan to the membranes as those from control rats. In addition, hepatic L tryptophan uptake via the high-affinity transport component correlated well with hepatic tryptophan 2,3-dioxygenase activity (r = 0.787). The present results indicate that the uptake of L-tryptophan into hepatocytes via a transport system which works under physiological conditions is closely related to hepatic tryptophan 2,3-dioxygenase activity. PMID- 2328026 TI - A novel diisopropylphosphofluoridate-sensitive phenylalanine arylamidase in human liver. AB - A diisopropylphosphofluoridate-sensitive (DFP-sensitive) arylamidase, which preferentially hydrolyzed Phe-p-nitroanilide (Phe-pNA), was purified from a crude extract of human liver by conventional chromatographic techniques. The purified enzyme gave a single band on SDS-polyacrylamide gel electrophoresis. The molecular weight of the enzyme was estimated to be 58,000 by SDS-polyacrylamide gel electrophoresis and 200,000 by chromatography on a column of Sephacryl S-300, suggesting that the enzyme is a trimer or a tetramer. The enzyme was inactivated in proportion to the amount of [3H]DFP incorporated with a [3H]DFP/subunit (58,000) molar ratio of 1.04. The data indicate that the enzyme belongs to the serine protease family. PMID- 2328027 TI - Infectious agents, immunity, and rheumatic diseases. AB - It should again be cautioned that these hypotheses are just that--hypotheses, for which there are some suggestive but not conclusive data. I have described these hypotheses using B27 and AS, and DR4 and RA. We are all aware that AS occurs in individuals who are B27 negative, and RA occurs in individuals who lack DR4. Although space does not permit further elaboration here, these hypotheses can be modified to take these additional associations into account. It should also be noted that even if the mechanisms advanced in these hypotheses prove to be true, different mechanisms may apply to different diseases, and several of these mechanisms may act in concert to produce disease. Nevertheless, these hypotheses provide a framework against which future experiments can be designed to further elucidate the relationship among infectious agents, immunity, and rheumatic diseases. PMID- 2328028 TI - T cell receptor expression and activation of synovial lymphocyte subsets in patients with rheumatoid arthritis. Phenotyping of multiple synovial sites. AB - Two-color flow cytometry analysis of peripheral blood and synovial lymphocytes from rheumatoid arthritis patients was performed using monoclonal antibodies directed against T cell subsets, T cell activation markers, and T cell receptors. The results showed an abnormally high percentage (greater than 15%) of CD3+, CD4 , and CD8- T cells expressing a specific receptor containing a gamma chain. Phenotypic analysis of lymphocytes infiltrating both knee joints of individual rheumatoid arthritis patients revealed very similar subset distribution and activation levels, despite strong differences in the clinical status between the 2 sites. PMID- 2328029 TI - Long-term immunomodulatory effects of T lymphocyte depletion in patients with systemic sclerosis. AB - We describe 2 patients with rapidly progressing systemic sclerosis that did not respond to conventional therapy, who were treated with a 5-day regimen of T cell specific antilymphocyte globulin. One patient had deteriorating pulmonary involvement, and the second patient had developed disabling skin disease with multiple ulcers and gangrene. Both patients showed improvement concomitant with almost complete elimination of CD4+ and CD8+ T lymphocytes. Regeneration of peripheral T cells required 60-90 days and was followed by a long-term inversion of the CD4:CD8 ratio. The persistent therapeutic effect in both patients correlated with the lack of CD4+ T cells and the predominance of CD8+ T cells. This suggests a crucial role of T cell immunity in the pathogenesis of systemic sclerosis. In vitro studies of regenerating T cells demonstrated that CD4+ helper/inducer cells were functionally competent. Alterations in the composition of the CD8+ population may explain the prolonged suppression of CD4+ T cells observed during the period of therapeutic benefit. PMID- 2328030 TI - C3 activation products correlate with antibodies to lipid A in pauciarticular juvenile arthritis. AB - IgM antibodies to monophosphoryl-lipid A were found to be elevated in sera from children with all forms of juvenile arthritis (JA) and systemic lupus erythematosus. Of more interest, in patients with pauciarticular JA, IgG antibody titers to monophosphoryl-lipid A were found to be correlated with the C3a concentration and the C3d:C3 ratio. Although the full specificity of these antibodies is unknown, they are the first that have been found to be correlated with complement activation products in any form of JA. PMID- 2328031 TI - Estrogen use and radiographic osteoarthritis of the knee in women. The Framingham Osteoarthritis Study. AB - Female participants of the Framingham Osteoarthritis Study (n = 831, mean age 73, age range 63-93) were evaluated for osteoarthritis with weight-bearing radiographs of the knee during 1983-1985. At each biennial examination (1963 1981), the women were asked about their use of estrogen during the previous 2 years. We categorized estrogen use as no use reported, use reported at 1 examination, or use reported at 2 or more examinations. We found no positive association of estrogen use with radiographic knee osteoarthritis after controlling for age, body mass index, age at menopause, physical activity, history of knee injury, and smoking. In fact, a modest but nonsignificant protective effect for both radiographic osteoarthritis (odds ratio 0.71, 95% confidence interval 0.42, 1.20) and severe radiographic osteoarthritis (odds ratio 0.66, 95% confidence interval 0.33, 1.32) was seen in women who reported estrogen use at 2 or more examinations. Subgroup analyses also showed no association between estrogen use and radiographic knee osteoarthritis. We conclude that estrogen use in women is not associated with an increased risk of radiographic knee osteoarthritis. PMID- 2328032 TI - Effects of tumor necrosis factor alpha and beta on resorption of human articular cartilage and production of plasminogen activator by human articular chondrocytes. AB - We examined the effects of recombinant human tumor necrosis factor (TNF) on human articular cartilage and chondrocytes in culture. Both TNF alpha and TNF beta stimulated cartilage matrix breakdown during prolonged culture and elevated the levels of plasminogen activator (PA) activity in both the supernatants and cell layers of cultured chondrocytes. Characterization of the PA activities by immunochemistry and by zymography following gel electrophoresis indicated that human chondrocytes produce both urokinase-type PA and tissue-type PA in response to TNF. The addition of both interleukin-1 and TNF alpha or TNF beta to chondrocyte cultures demonstrated a synergism between these cytokines in the generation of PA activity in the culture supernatants and cell layers. Our results suggest that both activated lymphocytes and monocytes may contribute to the cartilage destruction of inflammatory arthritis through their stimulation of chondrocytes with TNF beta and TNF alpha, respectively. Since PA is the only neutral proteinase reported to be elevated in TNF-stimulated chondrocyte cultures, it could have an important role in TNF-mediated cartilage destruction. PMID- 2328033 TI - Ly-1 B cells and disease activity in (New Zealand black x New Zealand white)F1 mice. Effect of total lymphoid irradiation. AB - The treatment of female (New Zealand black x New Zealand white)F1 mice with total lymphoid irradiation resulted in a prolonged remission of autoimmune disease activity. Total lymphoid irradiation-treated mice also showed a marked reduction of Ly-1 B cells, which lasted up to 3 months. The subsequent return of Ly-1 B cells to preirradiation levels was not associated with a simultaneous return of disease when measured by parameters such as IgG anti-DNA antibodies and spontaneous secretion of IgG by splenic cells. In cell sorting experiments, most of the cells spontaneously secreting IgG were found within the Ly-1- (CD5-) splenic B cell population. PMID- 2328034 TI - Serum activity that confers acid lability to alpha-interferon in systemic lupus erythematosus: its association with disease activity and its independence from circulating alpha-interferon. AB - We conducted a longitudinal evaluation of a patient with systemic lupus erythematosus who constitutively exhibited elevated levels of circulating alpha interferon (alpha-IFN). This study demonstrated that the serum levels of an activity that renders the endogenous alpha-IFN acid labile are positively correlated with disease activity. This IFN acid lability-inducing activity can also be found in the sera of systemic lupus erythematosus patients who have active disease but who do not have circulating alpha-IFN. PMID- 2328035 TI - The relationship of sulfoxidation status to efficacy and toxicity of penicillamine in the treatment of rheumatoid arthritis. AB - Penicillamine shows some structural similarities to carbocysteine. The ability to oxidize carbocysteine, i.e., the sulfoxidation status, shows a bimodal distribution in the general population. In this study, sulfoxidation status was determined in 50 of 60 rheumatoid arthritis patients receiving penicillamine. We found that poor sulfoxidation status, compared with good sulfoxidation status, was associated with a 3.9 times higher incidence of toxicity. PMID- 2328036 TI - Synovitis in angioimmunoblastic lymphadenopathy with dysproteinemia simulating rheumatoid arthritis. AB - We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia who developed a symmetric, rheumatoid-like, peripheral polyarthritis. Radiographs of the involved joints revealed soft tissue swelling without erosions or cartilage loss. Rheumatoid factor and fluorescent antinuclear antibodies were negative, and C-reactive protein and erythrocyte sedimentation rate were normal. Synovial fluid analysis showed an inflammatory effusion (white blood cell count of 3,500/mm3, with 76% polymorphonuclear leukocytes). A closed synovial biopsy of the wrist revealed a mononuclear infiltrate consistent with angioimmunoblastic lymphadenopathy with dysproteinemia. Monthly parenteral chemotherapy treatment with high-dose methyl-prednisolone and cyclophosphamide resulted in remission of all manifestations of disease, including arthritis. PMID- 2328037 TI - Advanced drug therapy in juvenile rheumatoid arthritis. PMID- 2328038 TI - Cricoarytenoid synovitis in ankylosing spondylitis. PMID- 2328039 TI - Comment on the article by Singh et al. PMID- 2328040 TI - Comment on the article by Lockshin. PMID- 2328041 TI - Comment on the letter by Hughes et al. PMID- 2328042 TI - Significance of multiple inferential tests. PMID- 2328043 TI - Antibiotic prophylaxis and regurgitant murmurs. PMID- 2328044 TI - Carnitine palmityltransferase deficiency and fixed muscle weakness. PMID- 2328045 TI - Traumatic spondylolisthesis of the axis with unusual distraction. A case report. PMID- 2328046 TI - Surface disinfectants. PMID- 2328047 TI - The use of the pins in plaster technique. PMID- 2328048 TI - The homeless. PMID- 2328049 TI - Cocaine. PMID- 2328050 TI - Depressive illness and abnormal sweat electrolytes. A case report. AB - False-positive sweat electrolyte levels are infrequently reported in adolescent psychiatric conditions. A case is reported and the interpretation of elevated sweat electrolytes discussed. PMID- 2328051 TI - Attention to prehospital care. PMID- 2328052 TI - Safety of grenz ray therapy. PMID- 2328053 TI - Tetracycline pleurodesis for persistent air leak. PMID- 2328055 TI - Safety first, not restraint. PMID- 2328054 TI - The evaluation of mental health care systems. PMID- 2328056 TI - Soviet alcoholism. PMID- 2328057 TI - Re: "Risk factors for spontaneous abortion and its recurrence". PMID- 2328058 TI - Concept of interpersonal distance in borderline personality disorder. PMID- 2328059 TI - Trabeculoplasty: results that can mislead! PMID- 2328060 TI - Idiopathic anaphylaxis. PMID- 2328061 TI - The effects of prone and supine positioning on arterial oxygen pressure. AB - An experimental study was conducted on 25 ventilated premature infants with RDS comparing PaO2 in the supine and prone positions. Analysis of the mean PaO2 showed significantly higher values in the prone position (p = .005). It is important for nurses to be aware of the implications of positioning on respiratory functioning and to integrate this knowledge in their practice. PMID- 2328062 TI - [Malignant mesothelioma of the pleura. Analysis of its immunohistochemical aspects]. AB - To evaluate the usefulness of immunohistochemistry in the diagnostic distinction between pleural mesothelioma and metastatic adenocarcinoma to the pleura, the authors studied formalin-fixed paraffin-embedded tissue sections from 14 pleural mesotheliomas and 20 primary adenocarcinomas of the lung, stomach, ovary and breast by using 16 commercially available antibodies to cytokeratin (KL1), vimentin, EMA, CEA, CA19.9, CA125, Egp 34 (detected by HEA 125), secretory component, S100 protein, SP1-beta 1, Leu M1, alpha-1-AT, alpha-1-ACT, lysozyme, desmin and factor VIII. Keratin positivity was found in all mesotheliomas and adenocarcinomas. A coexpression of keratin and vimentin was present in 8/14 (57%) mesotheliomas but only in 2/20 (10%) adenocarcinomas. CEA and CA 19.9 were detected in 80% and 65% of the adenocarcinomas respectively, but not in any of the mesotheliomas. Interestingly, two adenocarcinomas (of the ovary and the stomach) that failed to stain for CEA, were immunoreactive to anti-CA 19.9 antibody. Thus, the combined use of anti-CEA and anti-CA 19.9 antibodies results in staining 90% of the adenocarcinomas. S100 protein, SP1-beta and Leu M1 were also absent in mesotheliomas but present only in less than half of the adenocarcinomas. Adenocarcinomas and mesotheliomas did not significantly vary in reaction to the remaining above mentioned antibodies. The authors conclude that the coexpression of keratin and vimentin and the absence of CEA and CA 19.9 might be the best criteria in the distinction of mesothelioma from metastatic non mucosecreting adenocarcinoma. PMID- 2328063 TI - [Primary malignant non-Hodgkin's lymphoma of the breast. A study of 5 cases]. AB - Five cases of primary non-Hodgkin's lymphomas of the breast (stage IE in the Ann Arbor staging system) are described. No clinical or radiological feature has permitted to make the diagnosis before surgery. Histologically, all lymphomas are diffuse and B type. Three cases are high grade lymphomas, one of lymphoblastic type. Two cases are of lymphoplasmacytoid type, one of them associated with an occult invasive ductal carcinoma within the same breast, the other changing in high grade lymphoma at the recurrence time. Three of them reveal histological aspects of lymphoepithelial lesions and appear as mucosa-associated lymphoid tissue lymphomas (MALT). The differential diagnosis with a carcinoma is now easily done by immunohistochemical techniques. The importance of a diagnosis before surgery by cytopunction and drill-biopsy has to be emphasized, to prevent an useless mastectomy. PMID- 2328064 TI - [A case of malignant melanoma expressing epithelial cell markers in immunohistochemistry using paraffin sections]. AB - Recently, applications of immunohistochemical techniques for the cytoplasmic localization of intermediate filaments has produced advances in tumor diagnosis and characterization. We report a 58-year-old white male with a clinically and histologically typical metastatic malignant melanoma. This case was peculiar because the same neoplastic cells stained for both S-100 protein and keratin on paraffin embedded tissue. These facts illustrate how cautiously we must interpret the positivity of immunohistochemical technics. We thus insist on the importance of the clinical and basic histologic data for the diagnosis, in order to avoid errors. PMID- 2328065 TI - [Tubulo-papillary tumor of the kidney. Apropos of a case]. AB - Tubulopapillary tumors represent a particular group of the renal tumors. Beyond their characteristic histological features, these tumors can be distinguished from the other renal tumors by the frequency of stage I on histology and by a more favorable prognosis. PMID- 2328066 TI - [A method for the histologic study of the entire esophagus]. AB - The authors describe a method for sampling and embedding of oesophagectomy specimens which permits the study of the entire oesophagus with a minimum number of sections. Good localization of the lesions is achieved, and the simplicity of this method (accordion fold) makes it suitable for routine use. PMID- 2328067 TI - [Hepatic malacoplakia as a complication of polycystosis]. PMID- 2328069 TI - Just for students--survival techniques. PMID- 2328068 TI - Measuring and validating a nurse's caring performance. AB - This article describes the importance of clear, specific methods of evaluating nursing care. Nursing standards and job descriptions are explained within the context of performance evaluations for nurses. PMID- 2328070 TI - Dear Florence: legal musings for the 1990's. PMID- 2328071 TI - Orthopaedic nursing assessment. AB - This article stresses the relevance of using nursing models and presents a "nursing-focused" history format for gathering data from patients with orthopaedic conditions. PMID- 2328072 TI - "Learned helplessness" and the patient with progressive supranuclear palsy. AB - Progressive supra-nuclear palsy is a neurologically debilitating disease of unknown cause and with no effective treatment. Learned helplessness, a major cause of depression in the institutionalized elderly, is a feeling of worthlessness and powerlessness resulting in a decreased incentive to try. This article provides insight into these two problems and specific nursing interventions to enhance self care. PMID- 2328073 TI - What is an ethical decision? Ethics for contemporary nursing practice. PMID- 2328074 TI - The pitfalls of test reviews. PMID- 2328075 TI - The nursing health history. A powerful tool. PMID- 2328076 TI - Adult education for the patient with diabetes mellitus. AB - This article discusses the presentation of a diabetic education program. This material deals with various instructional concepts and methods of interacting with the Type II (NIDDM) Diabetic. PMID- 2328077 TI - The manager as coach. AB - The concept of "coach" is relatively new to nursing literature this term is not uncommon in management. The coaching concept has applications for nursing management. The role of coach, coaching in one-to-one vs. group situations, and the benefits of coaching for nursing management have been considered. PMID- 2328078 TI - "When would I use the nursing diagnosis of 'impaired social interactions related to grief and loss' and how should I intervene"? PMID- 2328079 TI - Listen. AB - The medical-surgical faculty in our Associate Degree in Nursing program developed an exercise to help students focus on the human side of nursing. PMID- 2328080 TI - Legal issues in experimental investigations of medications. PMID- 2328081 TI - Today's antidepressants. AB - Although antidepressant drugs are effective in reversing depression, all are capable of producing serious side effects. The nurse can help minimize potential problems through the use of effective patient teaching that begins as soon as the decision is made to initiate drug therapy and ends several weeks after therapy is discontinued. PMID- 2328082 TI - Credibility & the nurse. AB - This article addresses the issue of credibility and the nurse by describing how and why a nurse becomes credible in relating to others. PMID- 2328083 TI - A single day of alcohol exposure during the brain growth spurt induces brain weight restriction and cerebellar Purkinje cell loss. AB - The period of rapid brain growth that occurs relatively late in development has been shown to be vulnerable to alcohol-induced brain growth deficits and neuron loss in rats using repeated daily exposure to alcohol. This study examined whether a condensed exposure (binge) restricted to a single day during this period would be sufficient to restrict brain growth and produce neuron depletion. Using artificial rearing, alcohol was given to neonatal rats in two consecutive feedings on postnatal day 4, using a total dose of either 6.6 g/kg or 3.3 g/kg. The higher dose produced mean peak blood alcohol concentrations of 362 mg/dl, while the lower dose produced mean peak BACs of 153 mg/dl. The higher dose significantly restricted whole brain, forebrain, cerebellum and brain stem weights on postnatal day 10, with the cerebellum being most severely reduced. Cerebellar Purkinje cells, counted from a 2-microns section from the midsagittal vermis, were significantly reduced in the 6.6 g/kg group. Purkinje cell loss relative to controls was significant in the most lobules (I-V, IX and X), but, notably, was not significant in the later maturing regions (lobules VI and VII). The 3.3 g/kg group had no significant reductions in regional brain weights. Although the overall number of Purkinje cells was nonsignificantly reduced relative to controls, the 3.3 g/kg dose did produce significant loss of Purkinje cells in lobule II. Exposure to high peak BACs, even for a relatively short period during the brain growth spurt, constitutes a substantial risk to the developing brain, and even a moderate exposure may result in loss of more vulnerable neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328084 TI - Similarity of taste reactivity responses to alcohol and sucrose mixtures in rats. AB - The orofacial responses of rats following infusion of taste solutions were examined in two experiments. In the first experiment, naive rats were presented with a 6% alcohol solution and three sucrose mixtures (sucrose combined with quinine hydrochloride, hydrochloric acid, and sodium chloride, respectively) on separate trials and the resulting taste reactivity was examined. The only difference among the solutions was that alcohol elicited a significantly larger number of aversive responses (e.g., gapes, passive drips) than the sucrose mixtures. In the second experiment, naive rats were trained to avoid 6% alcohol using standard conditioned aversion procedures; rats were then tested for reactivity to the three sucrose mixtures and the alcohol solution. With the alcohol solution, trained rats displayed significantly fewer ingestive responses and significantly more aversive responses than control rats. The response of trained rats to the sucrose + quinine solution was similar to that of alcohol: fewer ingestive responses and more aversive responses than control rats. The number of aversive responses to the alcohol and the sucrose + quinine mixture by the trained rats did not differ significantly. Reactivity to the sucrose + hydrochloric acid and sucrose + sodium chloride solutions did not differ between trained rats and control rats. The results suggest that a sucrose + quinine solution has a perceived taste (as revealed by elicited orofacial reflexes) similar to alcohol and that the sucrose mixture is avoided by rats with alcohol aversions because it is unpalatable. PMID- 2328085 TI - The effects of chronic ethanol treatment on endothelium-dependent responses in rat thoracic aorta. AB - The purpose of this study was to investigate the effects of chronic ethanol consumption on blood pressure and vascular responses, specifically, the possible alterations in endothelium-dependent relaxation which are associated with ethanol induced hypertension in the rat model. Male rats received ethanol in drinking water for 13 weeks. Systolic pressure was recorded weekly. Following treatment, segments of thoracic aorta with and without intact endothelium were used to generate relaxation-response curves to the endothelium-dependent agents, acetylcholine, ATP and bradykinin, as well as the endothelium-independent agents, adenosine and sodium nitroprusside. Mean systolic pressures at the end of the treatment period were: 127.8 +/- 1.2 and 151.1 +/- 1.3 mmHg for controls and ethanol-treated rats, respectively. Ethanol treatment did not affect the relaxation produced by either acetylcholine, ATP or sodium nitroprusside in aorta with or without endothelium. In contrast, ring segments with intact endothelium from ethanol-treated rats exhibited augmented relaxation in response to both adenosine and bradykinin compared to controls. Removal of the endothelium abolished the relaxation produced by bradykinin in both groups. Although removal of the endothelium had no effect on the relaxation produced by adenosine in the control group, it attenuated the adenosine-induced relaxation in the ethanol treated group back to control levels. These data suggest that chronic ingestion of ethanol causes elevated blood pressure and augments the endothelium-dependent relaxation to bradykinin. These findings also suggest that chronic ethanol treatment can cause the appearance of an endothelium-dependent component in the relaxation produced by adenosine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328086 TI - Continuous monitoring of brain ethanol levels by intracerebral microdialysis. AB - A method is described which allows simultaneous collection of blood and perfusate of discrete brain regions from an individual animal over several hours. This procedure involves catheterization of a peripheral blood vessel (jugular vein) and the insertion of a microdialysis probe into a specified brain area (lateral hypothalamus) for sampling of blood and brain perfusate, respectively. Using this procedure, levels of ethanol in blood and brain perfusates were determined by scintillation counting following administration of [14C]-ethanol (20 mu Ci) to adult male rats at a dose of 0.8 or 2.4 g/kg. Ethanol levels in brain and blood as well as the time-course of disappearance were dependent on the dose administered. Peak blood levels were observed in the first sample taken (i.e., at 10 min), whereas a slight delay was noted in the time to peak level in brain. At subsequent time points, a good correlation was observed between blood and brain perfusate radioactivity levels although perfusate levels were slightly lower. It is concluded that this approach will prove useful for investigating the molecular and cellular mechanisms of action of ethanol by enabling the direct correlation of blood and brain ethanol levels with various behavioral, electrophysiological and/or biochemical measures. PMID- 2328087 TI - The influence of control over appetitive and aversive events on alcohol preference in rats. AB - The effect of control of food reinforcement or shock termination on alcohol drinking was examined in two experiments. In the first experiment, rats unable to control the delivery of food pellets preferred alcohol more than rats which had control over food. Similarly, in the second experiment, rats unable to control electric footshock termination preferred alcohol more than rats which could escape shock. These results showed that the psychological dimension of control over environmental events influences alcohol preference in rats. PMID- 2328088 TI - Effects of chronic alcohol intake and withdrawal on the prefrontal neurons and synapses. AB - Previous studies demonstrated that alcohol induces marked deterioration of the cerebral cortex. However, quantitative evaluations of neurons and synapses of the prefrontal cortex from chronic alcohol-fed and withdrawn animals are nonexistent, in spite of the functional implications that can underlie structural changes in this cortical area. To achieve this evaluation, we used groups of rats alcohol fed for 6, 12 and 18 months, their respective controls as well as groups of rats alcohol-fed for 6 and 12 months and then switched to water for 6 months- withdrawal groups. The thickness of the prelimbic cortical layers I-III was reduced in the alcohol-fed and withdrawal groups. A significant reduction in the density of cells was found, which was more marked after withdrawal. Conversely, the density of synapses increased after alcohol exposure and withdrawal; such numerical shifts lead to a significant increase in the synapse-to-neuron ratio. These results indicate that the cortical circuitry of the prelimbic cortex is vulnerable to prolonged periods of alcohol exposure and withdrawal and allow to advance the view that the alterations can induce functional implications. PMID- 2328089 TI - Effect of ethanol-generated free radicals on gastric intrinsic factor and glutathione. AB - The oxidation of acetaldehyde (generated from the metabolism of ethanol) by oxidases such as xanthine oxidase generates free radicals which can mobilize ferritin iron, alter hepatic glutathione and produce lipid peroxidation. The stomach, a site of ethanol metabolism and rich in xanthine oxidase, was studied with respect to the effects of ethanol on intrinsic factor (IF) binding of vitamin B-12 as well as gastric glutathione (GSH). Incubations of gastric homogenates with acetaldehyde-xanthine oxidase inhibited the B-12 binding ability by IF. A large acute dose of ethanol in vivo (5 g/kg, conc. greater than 40% w/v) decreased gastric IF binding of B-12 and depressed gastric GSH; these effects were markedly attenuated by the feeding of sodium tungstate which inhibited xanthine oxidase. Changes in B-12 binding paralleled changes in gastric GSH. Scatchard plots of IF binding of B-12 for homogenates suggested decreased number of binding sites rather than altered affinity. In conclusion, the gastric metabolism of ethanol generates free radicals which alter IF binding of B-12, depress gastric GSH and may play a role in alcohol-induced gastric injury. PMID- 2328090 TI - Effect of ethanol on brain catecholamines in rat lines developed for differential ethanol-induced motor impairment. AB - The importance of the central catecholamines, with the emphasis on the noradrenergic neurons in the differential sensitivity to ethanol between the AT (alcohol-tolerant) rats selected for low and the ANT (alcohol-nontolerant) rats selected for high sensitivity to ethanol-induced (2 g/kg) motor impairment, was clarified by studying the effects of ethanol (2 and 4 g/kg, IP) on the utilization of norepinephrine (NA) and dopamine (DA), and on the metabolism of NA. The utilization of the catecholamines was estimated from the disappearance of the amines after inhibition of the brain tyrosine hydroxylase by alpha-methyl-p tyrosine (200 mg/kg, IP), given 15 min after the administration of ethanol. The formation of 3-methoxy-4-hydroxy-phenylglycol (MHPG) was used as an estimate of NA metabolism, and was measured 30 min after the administration of ethanol. The basal utilization rate of NA and DA was similar between the two rat lines, but the increased formation of MHPG suggested that the naive AT rats had a higher noradrenergic activity in the limbic forebrain, hypothalamus, and cerebellum than did ANT rats. In the brain of both lines, ethanol accelerated the utilization and metabolism of NA in the same manner. Ethanol also increased the utilization of DA in the limbic forebrain of the AT and ANT rats. The higher sensitivity of the ANT rats' DA neurons to ethanol in the limbic forebrain and striatum was revealed by the significant rat line X ethanol interaction. The present findings suggest that the AT and ANT rats differ in the dopaminergic, but not in the noradrenergic responses to ethanol. PMID- 2328091 TI - Initial acceptance of ethanol: gustatory factors and patterns of alcohol drinking. AB - Individual differences related to taste, determined by prior two-bottle tests of quinine and saccharin selection against water, were found to be related to the initial selection of 15% ethanol solution during the first week of access by 60 randomly bred male rats. The 36 rats that drank the least alcohol during the first week (mean +/- SE: 0.49 +/- 0.06 g/kg/day), however, greatly increased their intake during the second and third weeks, to the level of the 24 initially high alcohol drinkers (4.07 +/- 0.39 g/kg/day during 1st week), and the influence of gustatory factors was no longer apparent. Subsequently, the initially low rats drank less alcohol when saccharin was the alternative fluid. The results can be interpreted as showing that initially low rats, that only drank rather large amounts of alcohol after prolonged exposure, resemble Cloninger's Type 1 alcoholics not only in this temporal pattern but also in being high in novelty seeking, and low in harm avoidance and reward dependence, and that the initially high rats that spontaneously drank rather large amounts even in the first week show the opposite characteristics and resemble Type 2 alcoholics. Although these rats are not themselves models for alcoholism, the results nevertheless suggest it might be possible to develop two separate animal models for the two types of alcoholism. PMID- 2328092 TI - Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AB - The kinetics of appearance and specificity of HIV-1 neutralizing antibodies was studied in four individuals. HIV-1 was isolated during symptomatic primary HIV-1 infection and repeatedly thereafter, and tested against autologous sera collected in parallel. Our patients developed isolate-specific low-titer neutralizing antibodies within 2-4 weeks, and the titers to the first isolates increased with time. We documented the emergence of virus variants with reduced sensitivity to neutralization by autologous, but not heterologous, sera in three patients. These virus variants were not, however, resistant to neutralization per se, since they were readily neutralized by the positive control serum. Our patients did not develop antibodies capable of neutralizing the new virus variants during the observation period. This suggests either a failure of the immune system to respond to the new virus variants or a mechanism by which the virus evades detection by the immune system. The emergence of neutralization-resistant virus variants was not directly correlated with disease progression since two patients have remained asymptomatic after the emergence of such virus variants. It is, however, likely that the emergence of virus variants which the patient fails to neutralize in the long run contributes to disease progression. PMID- 2328093 TI - Anti-CD4 autoantibodies and screening for anti-idiotypic antibodies to anti-CD4 monoclonal antibodies in HIV-seropositive people. AB - The cell-surface antigen CD4 is the major receptor for HIV. Anti-CD4 autoantibodies and anti-idiotypic antibodies to murine monoclonal anti-CD4 antibodies have been described in HIV-infected people. Ninety-seven sera from HIV infected people at all stages of disease were examined for the presence of anti idiotypic antibodies to three anti-CD4 monoclonal antibodies. None were found. The same sera were screened for antibodies reactive with soluble CD4, and five (5.2%) were positive. These antibodies did not recognize native CD4, and it is thought unlikely that they arise as anti-idiotypes to anti-gp120 antibodies. PMID- 2328094 TI - The interferon-induced Mx-homologous protein in people with symptomatic HIV-1 infection. AB - Twenty-six people with symptomatic HIV-1 infection were screened for the presence of interferon (IFN) alpha and IFN alpha antibodies in their sera and the presence of the IFN-induced intracellular Mx-homologous protein in their peripheral blood leukocytes. Eleven people had measurable IFN alpha levels ranging from 1 to 40 IU/ml. None of the sera tested was positive for IFN alpha binding or IFN alpha neutralizing antibodies in the assays employed. Twenty-five of the 26 people had significant levels of the Mx-homologous protein in their peripheral mononuclear cells. The Mx concentrations varied from 0.3 to 6 U/ml in the people studied. IFN alpha-positive people had significantly higher levels of the Mx homolog than IFN alpha-negative people (P less than 0.03). Furthermore, the Mx homolog content in Walter-Reed class 2 people was significantly lower than in Walter-Reed class 5/6 people (P less than 0.01). Our results suggest that the IFN system is activated in more than 90% of the people with lymphadenopathy-associated syndrome, AIDS related complex and AIDS. Since acid-labile IFN alpha can induce the Mx homolog in vitro endogenously produced IFN alpha seems likely to be responsible for the high Mx homolog levels detected. PMID- 2328095 TI - The influence of age on the latency period to AIDS in people infected by HIV through blood transfusion. AB - We collected information on the development of clinical signs and laboratory results from a cohort of 58 people infected with HIV through blood transfusion. The observation time ranged from 36 to 100 months. Belonging to the older age group at the time of transfusion was found to be an important factor for rapid progression to AIDS. Sex or physical health at the time of transfusion did not influence the latency period. PMID- 2328096 TI - HIV infection among lower socioeconomic strata prostitutes in Nairobi. AB - A cohort of 418 lower socioeconomic strata prostitutes were enrolled in a study of the epidemiology of sexually transmitted diseases (STDs) between January and April 1985. Sixty-two per cent of the women were seropositive for HIV infection at enrollment. Significant associations were found between HIV seropositivity and Tanzanian origin (OR = 2.12, CI 95% = 1.18-3.81, P less than 0.03), younger age, a shorter duration of prostitution, reduced fecundity, use of oral contraceptives (OR = 1.8, CI 95% = 1.1-2.9, P less than 0.05) and genital ulcer disease (OR = 3.32, P less than 0.00001). No associations were noted with other STD. Stepwise logistic regression analysis confirmed independent associations between HIV infection and Tanzanian origin (OR = 2.27, CI 95% = 1.25-4.14, P less than 0.007), reduced fecundity (OR = 0.83, CI 95% = 0.74-0.94, P less than 0.003), oral contraceptive use (OR = 2.02, CI 95% = 1.22-3.35, P less than 0.006) and duration of prostitution (OR = 0.39, CI 95% = 0.23-0.65, P less than 0.004). Oral contraceptives may increase susceptibility to HIV or may be a marker for other factors which increase risk of acquisition. Further studies are necessary to confirm this association. PMID- 2328097 TI - Psychological responses to serological testing for HIV. AB - To determine the emotional impact of serological testing for HIV, 218 physically asymptomatic adults were evaluated in a confidential clinical setting 2 weeks before HIV test notification, immediately before and after notification, and 2 and 10 weeks later. All received extensive pre- and post-test counseling. The 179 seronegatives reported one or more HIV risk behaviors: homosexual intercourse (n = 111), heterosexual intercourse with possibly infected partners (n = 62), intravenous drug use (n = 20). Immediately after notification, seronegatives had significant decreases in visual analogue scale (VAS) measures of anxiety, depression, fear of getting AIDS, and fear of having infected others. Reductions were sustained at both follow-up assessments and were complemented by significant reductions on standardized self-reported measures of anxiety (Spielberger State Anxiety Inventory, SAI), depression (Beck Depression Inventory, BDI), and psychiatric symptoms (Brief Symptom Inventory, BSI) as well as by clinical ratings of depression (Hamilton Depression Rating Scale, HDRS). Of 39 seropositives, 35 had homosexual risk behaviors, seven had been intravenous drug users (IVDUs; four of whom were homosexual men), and one was a female partner of an IVDU. Immediately after notification, VAS measures of their anxiety were not significantly increased, and at 10 weeks after notification, their VAS measures of distress and mean scores on BDI, SAI and BSI were significantly lower than at entry. Their HDRS ratings were not significantly increased. PMID- 2328098 TI - HIV status and changes in risk behaviour among intravenous drug users in Stockholm 1987-1988. AB - An HIV study initiated in January 1987 is being conducted at the Remand Prison in Stockholm, Sweden, in order to follow HIV seroprevalence and HIV risk behaviour among intravenous drug users (IVDUs) in Stockholm. Up to December 1988 1152 arrested and detained IVDUs were interviewed about risk behaviour and tested for HIV antibodies. Amphetamine, which is the main IVDUs drug used intravenously in Stockholm, was used by 958 of these, while heroin was used by 194. HIV seroprevalence was 12.6%: 5.9% among the amphetamine and 45.5% among the heroin users. The HIV incidence was calculated to be 0.9% in 1987 and 1.2% in 1988, higher for amphetamine than for heroin users. Some risk reduction was reported regarding needle sharing, but less so regarding sexual behaviour. PMID- 2328099 TI - Epidemiology of HIV-1 infection in the island of Sardinia. HIV Sardinia Group. PMID- 2328100 TI - Serum level of TNF alpha in HIV-infected individuals. PMID- 2328101 TI - Structure of 1,4-cubanediyldiammonium bis(trinitromethanide). AB - C8H12N2+.2CN3O6-, Mr = 436.27, monoclinic, C2/m, a = 14.298 (2), b = 8.408 (1), c = 7.354 (2) A, beta = 103.42 (2) degrees, V = 859.9 (5) A3, Z = 2, Dx = 1.68 g cm 3, lambda(Mo K alpha) = 0.71069 A (graphite monochromator), mu = 1.66 cm-1, F(000) = 448, T = 293 K, final R = 0.039 for 672 reflections with I greater than or equal to 3 sigma(I). The cubanediyldiammonium cation and trinitromethanide anion have 2/m and m crystallographic symmetries, respectively. The cation is linked to six trinitromethanide anions, three at each end, by a total of 12 N- H...O hydrogen bonds through the six cation H atoms. The cubane cage has a local threefold axis of symmetry along the long axis (N1...N1) of the cation and undergoes a large librational motion, 17 degrees r.m.s. amplitude, about this axis. PMID- 2328102 TI - Diisopropylammonium chloride. AB - C6H16N+.Cl-,Mr = 137.65, orthorhombic, P2(1)2(1)2(1), a = 7.825 (4), b = 8.257 (1), c = 13.268 (2) A, V = 857.3 (5) A3, Z = 4, Dx = 1.066 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 3.6 cm-1, F(000) = 304, T = 295 K, R = 0.030 for 556 observations (of 901 unique data). Each H on the N atom is hydrogen bonded to a Cl atom. N--H...Cl bond lengths (N--Cl distance) are 3.180 (3) and 3.163 (3) A with N--H...Cl angles 176 (2) and 175 (2) degrees respectively. Each Cl atom is involved in two hydrogen bonds. The cation has an approximate twofold axis of symmetry. PMID- 2328103 TI - [The irrefutable benefits of courses for alcohol intoxicated drivers]. AB - The benefit of courses for alcohol conspicuous drivers, as it is shown by Winkler et al. in a careful and clear manner, still is to be considered as not refuted so far. The participants in courses (experimental group), who according to their situation were supposed to have a substantial higher rate of recidivism, had an actual recidivism-rate, which was significantly lower than the rate of the control group. Interpreting the present scientific literature correctly, Hundhausen's (1989) five main arguments against the results of Winkler et al., which all his further conclusions depend on, are not right. PMID- 2328104 TI - [Cough syncope as a cause of traffic accident]. AB - The rare tussive syncope syndrome, which can lead to a road traffic accident, occurs almost solely in the male aged 40 years and over with a pyknic to athletic physique, who suffer from obstructive respiratory tract disease and/or pulmonary emphysema. Frequently there is a correlation between the illness and alcohol and tobacco consumption. Loss of consciousness lasting only a few seconds occurs a few seconds after a coughing attack leaving behind a short loss of memory. Tussive syncope can be a solitary event, but can also occur up to thirty times a day. In foro, characteristically the link between a heavy coughing and loss of consciousness as well as the type of person make diagnosis easier. The suitability of the subject to hold a driving licence should be judged carefully and on individual criteria. PMID- 2328105 TI - [Legal requirement of medical-psychological examination of drunk driving offenders: should other than blood alcohol concentration and "particular circumstances" of the individual case be considered?]. AB - According to a footnote of the directions for driver selection tests ("Eignungsrichtlinien") of December 1, 1982, a medical and psychological examination can be disposed also with first drunkenness offenders. Against the design, partially realised in practice, to use not only the blood alcohol level as a screening criterion but also special circumstances of the case, objections are brought forward. PMID- 2328106 TI - [Modification of Alcomat breath alcohol measurements by various substances of routine use (mouthwash, perfume, after-shave lotion etc]. AB - This paper presents the reliability of the "BAC-values" (AAKB) at the application and consumption of substances of daily usage, ascertained with the help of the "Alcomat". Hereby it was found that especially at the application of preparations for the mouth- and throat-hygiene like toilet lotion values of max. 0.30% had to be taken into consideration, even if there was no "alimentary" alcohol existing in the blood. PMID- 2328107 TI - [Developments in street traffic from 1975 to 1988 from a statistical viewpoint]. AB - The author gives a report on the events in road traffic in the Federal Republic of Germany under statistical aspects--doing so he continues a tradition, which is in practice by the "Kraftfahrt-Bundesamt" (Federal Motor-Vehicle Board) since 1971. Since individual road traffic and the density of traffic are rising, the number of traffic accidents is increasing nearly proportionally to the development of the rolling stock and the quantity of driving. A small positive development seems to be seen in the rate of accidents by drunken driving. It may be, that this is a result of the information-campaigns. But nevertheless: each alcoholized driver always has to expect particularly severe consequences from an accident. PMID- 2328109 TI - [Social psychological and sociocultural aspects of alcohol drinking and alcoholic intoxication behind the wheel]. AB - The paper deals with socio-psychological and socio-cultural problems of drunken driving and of alcohol-consumption in general. It is the intention to make evident how the way to show a certain behavior is imbedded in more comprehensive conditions. The contradictory relations between the role of individual traffic and of alcohol consumption in a society on the one hand and the phenomenon of drunken driving on the other hand are pointed out, as well as the different valuation of social drinking and alcohol dependence. The way of profanation of the drug "alcohol" and the importance of social influence on consumption and effect of the drug are shown, taking into consideration the subjective position of the individual in the society. Finally the role of the state and possibilities of a systemic approach against drunken driving are dealt with. PMID- 2328108 TI - [Influence of breath volume on alcohol analysis]. AB - In order to obtain reliable results in breath-alcohol analysis it is necessary to consider alveolar air. In former examinations of the question, which part of expired air contains almost pure alveolar air, a separation between the influence of temperature and volume had not been made. Only after a temperature correction has been performed the influence of volume can clearly be seen in drinking experiments. Measurements undertaken with the ALCOMAT clearly show the influence of varied breathing techniques on the results of breath-alcohol determinations. The demand of a minimum volume in the breath test is not sufficient by itself. In order to get a correct result the expiration volume should be more than 70% of the subject's vital capacity. In case of an expired volume remarkably below 50% of the vital capacity the measured values can be more than 10% below the expected values. Such big deviations can only be the result of a deliberate inspiration and expiration technique of the subject. PMID- 2328110 TI - Fragmentation within otolaryngology-head and neck surgery. PMID- 2328111 TI - Segmental mandibular regeneration by distraction osteogenesis. An experimental study. AB - We report the use of distraction osteogenesis for segmental mandibular regeneration. This technique has been used in thousands of patients in the Soviet Union to regenerate as much as 30 cm of tubular bone in the extremities. However, we are unaware of previous experimental or clinical reports of segmental mandibular regeneration by distraction osteogenesis. In a canine model, 2.5-cm segmental mandibular defects were filled with regenerate bone in 25 days at a rate of 1.0 mm/d using bifocal distraction osteogenesis. The diameters of the regenerate segments were comparable with preexisting mandible, and all animals resumed normal oromandibular function following regeneration. The regenerate bone was evaluated radiographically, angiographically, and histologically. In the control group without distraction osteogenesis, the segmental defects failed to fill with regenerate bone. The theoretical basis for distraction osteogenesis, a detailed description of the technique, and a review of previous studies on experimental mandibular lengthening are presented. PMID- 2328112 TI - Topical and oral treatment of chronic otitis media with ciprofloxacin. A preliminary study. AB - The clinical and bacteriological efficacy of ciprofloxacin was studied in three groups composed of 20 patients each, all of whom were affected by chronic otitis media in the acute stage. Ciprofloxacin was randomly administered according to the following schedules for 5 to 10 days: 250 mg orally twice a day (group A); 3 drops (250 micrograms/mL in saline solution) locally twice a day (group B); and both of the previous treatments twice a day (group C). A high percentage of favorable clinical response (100% and 95%) and bacteriological eradication (95% and 85%) was observed in groups B and C. A low percentage of patients (65% and 40%) were clinically and bacteriologically cured by the oral therapy (group A). No worsening of the audiometric and vestibular function was observed after local therapy. The results of this preliminary study suggest that the use of topical ciprofloxacin is effective in curing chronic otitis media, even when it is caused by Pseudomonas (47% of the total bacterial detections). PMID- 2328113 TI - Observations of the anterior epitympanic recess in the human temporal bone. AB - The structure of the anterior epitympanic recess was examined in 50 human temporal bones. The recess was found in 48 temporal bones (96%) and showed three different structural types. In type A, the least developed type (38%), a main cavity is seen above the tensor tympanic fold. The recess is divided into two cavities by the tensor tympanic fold, which stretches to the anterosuperior tympanic tegmen in type B, the intermediate type (40%). The tensor tympanic fold is fused with the superior mallear fold in type C, the best-developed type (18%), with the recess being contiguous with the eustachian tube. The shape of the anterior epitympanic recess is influenced by the ratio between the cavities above and below the tensor tympanic fold, ie, by the embryologic development of the saccus anticus and the anterior saccule of the saccus medius. The structural variations in this recess must be kept in mind during the surgical management of middle ear diseases. PMID- 2328114 TI - Trends in rehabilitation after cochlear implantation. AB - Although postimplant rehabilitation is generally considered to be an important aspect of a cochlear implant program, the literature reports widely varying practices in the implementation of such programs. The National Institutes of Health consensus statement on cochlear implantation (May 1988), while recognizing that aural rehabilitation facilitates maximal use of the implant, offers no specific guidelines or recommendations. A questionnaire survey was made of over 200 otolaryngologists to determine current practices in a variety of aspects of their cochlear implant programs. Results were obtained from a total of more than 1400 patients, including adults, adolescents, and children. Rehabilitation is an integral part of the cochlear implant program in the vast majority of active programs surveyed. General aspects of cochlear implant programs, as well as those of rehabilitation programs in particular, are discussed. PMID- 2328115 TI - Pulmonary atelectasis after reconstruction with pectoralis major flaps. AB - Forty-four patients were reviewed to determine the incidence of atelectasis following pectoralis major myocutaneous flap reconstruction of head and neck defects. Patients underwent tumor resection with subsequent pectoralis major myocutaneous flap reconstruction (flap group, n = 24) or another major head and neck procedure (control group, n = 20). Chest roentgenograms taken on the first postoperative day were scored for atelectasis by preestablished criteria. Sixty five percent of control and 70% of flap patients demonstrated postoperative atelectasis roentgenographically. The flap patients with skin paddles larger than 40 cm2 had a 60% incidence of major atelectasis compared with 5% in control patients. The skin island area was strongly correlated with the atelectasis score in the flap group. These results suggest that atelectasis is common following pectoralis major myocutaneous flap reconstruction of head and neck defects. As well, decreased chest wall compliance after primary closure of large donor defects may contribute to the atelectasis observed. PMID- 2328116 TI - Split-palate approach for gold grain implantation in nasopharyngeal carcinoma. AB - Although nasopharyngeal carcinoma is radiosensitive, local failure after external radiotherapy is not uncommon and management of persistent or recurrent disease is a therapeutic challenge. The present review reports the use of brachy-therapy in the form of gold grain (198Au) implants in the treatment of 23 patients with recurrent or persistent primary nasopharyngeal carcinoma. The split-palate approach was employed in the insertion of the gold grains. This approach allows adequate exposure of the nasopharynx and accurate positioning of the implants. Implantation was successful in 21 patients, and local tumor control was achieved in 17 patients (81%) after a median follow-up of 23 months. Palatal fistula developed in 6 patients (26%): 5 healed with conservative management, and 1 had no functional disturbance. There was no operative mortality, and morbidity of the operation was minimal. PMID- 2328118 TI - The cutaneous scapular free flap in head and neck reconstruction. AB - Successful surgical reconstruction of complicated soft-tissue defects of the head and neck region has been greatly enhanced by free-revascularized tissue transfers. The scapular free flap has become a favored reconstructive option in our department and has been reported previously for one-stage mandibular reconstruction. This flap can also be transferred as a cutaneous free flap. We present our clinical experience with the fasciocutaneous scapular free flap and review the anatomy, surgical technique, and utility of this versatile flap. PMID- 2328117 TI - Combined median mandibulotomy and Weber-Fergusson maxillectomy. AB - Monoblock surgical resection in combination with radiotherapy remains the most effective method of treatment for advanced carcinoma of the maxillary sinus. Extension of antral carcinoma into the infratemporal and pterygopalatine fossae decreases the probability of achieving an all-encompassing resection via the classic anterolateral Weber-Fergusson approach because of limited posterior access. Temporal and lateral infratemporal fossa approaches have been described and involve either mobilization of the zygomatic arch or a lateral mandibular osteotomy, respectively. We report the use of a median labiomandibulotomy combined with the Weber-Fergusson approach for lesions extending posteriorly. The labiomandibulotomy with paralingual extension along the floor of the mouth allows rotation of the coronoid process laterally and exposes the infratemporal fossa to its posterior margin. We present two cases in which this approach was used to extirpate lesions that had extended posteriorly. Relevant anatomy, operative technique, potential complications, and limitations, as well as a comparison with other methods of exposure, are discussed. PMID- 2328119 TI - The otolaryngologic manifestations of Pelizaeus-Merzbacher disease. AB - Pelizaeus-Merzbacher disease is a condition of central nervous system dysmyelination. We describe a familial series in which both otologic and laryngologic abnormalities were present. The diagnosis of this invariably fatal disorder can be made on a clinical and/or pathologic basis. As the otolaryngologic manifestations are often the first to appear, the consulting head and neck surgeon may be essential in the initial diagnosis of this hereditary disease. PMID- 2328120 TI - Pathologic quiz case 1. Intramuscular angiolipoma. PMID- 2328121 TI - Pathologic quiz case 2. Malignant melanoma. PMID- 2328122 TI - An examination of the intra-SMSA distribution of carbon monoxide exposure. AB - Although fixed-site monitoring data have been used to estimate the spatial pattern of human exposure, the intra-urban distribution of actual exposure has not been documented. This paper used the data collected during the Environmental Protection Agency's (EPA) field investigation of personal exposure to carbon monoxide (CO) to investigate the nature of the distribution of CO with respect to residential location in the Washington, D.C. SMSA. Dot-distribution maps and analysis of variance were used to document the spatial pattern of individual level in-home CO concentrations. The results show sampled individuals living in the SMSA center are exposed to statistically significantly higher levels of CO than are those living in the suburbs. The most important implications of this work are for exposure modeling. Further investigation is needed to determine whether incorporation of a geographic component will improve exposure prediction. PMID- 2328123 TI - Passive sampling for ozone. PMID- 2328124 TI - Fugitive emissions of NO2 from vented gas appliances in residences--a pilot study. PMID- 2328125 TI - Temporal and spatial transcriptional regulation of the aboral ectoderm-specific Spec genes during sea urchin embryogenesis. AB - mRNAs for Spec 1 and Spec 2 of Strongylocentrotus purpuratus and LpS1 of Lytechinus pictus accumulate only in the aboral ectoderm of developing embryos. In vitro nuclear transcription assays were done to study the transcriptional regulation of these cell type-specific genes. Spec 1, Spec 2c, and Spec 2d genes all appeared to be transcriptionally activated at the late cleavage-early blastula stage of S. purpuratus. Differences in the relative transcription rates during development appeared to play a major role in determining the relative levels of the various Spec mRNAs. The L. pictus LpS1 gene was transcriptionally activated at a similar developmental time as the corresponding S. purpuratus genes. Nuclei from gastrula or pluteus ectodermal and endodermal/mesodermal cell fractions were used to demonstrate that Spec 1 and LpS1 genes were transcriptionally active in ectoderm nuclei but not in endoderm/mesoderm nuclei, suggesting that in vivo the Spec 1 and LpS1 genes are spatially controlled at the transcriptional level. Estimations of the absolute rate constants for Spec 1 transcription were made at the late cleavage, mesenchyme blastula, and midgastrula stages. Calculations using these rate constants and the known levels of Spec 1 mRNA suggested that Spec 1 mRNA stability gradually increased throughout development. PMID- 2328126 TI - Identification of extracellular proteins in the rat cumulus oophorus. AB - We have examined the proteins associated with the mucous matrix of the rat cumulus oophorus and compared them to the composition of rat serum, follicular fluid, ampullary fluid, and oocyte-cumulus cell extract. The cumulus matrix was dispersed using Streptomyces hyaluronidase, and the proteins were analyzed by high-resolution two-dimensional polyacrylamide gel electrophoresis and compared with proteins of the serum, proestrous follicular fluid, and postovulatory ampullary fluid and extracts of oocytes and cumulus cells. In addition to albumin and transferrin, which were common to all the fluids analyzed, the cumulus material contained many proteins in common with the follicular fluid and the ampullary fluid. However, the protein extract of the cumulus matrix also contained four major proteins not present in the other fluids analyzed. Two of these proteins were acidic and heterogenous in charge and size (MW approximately 81,000 and 100,000). The other two proteins were more basic and occurred at MW approximately 90,000 and 150,000. Our results show that the extracellular matrix of the cumulus contains proteins that are not present in the fluids that surround the oocyte. PMID- 2328127 TI - Penetration of intact bovine ova with ram sperm in vitro. AB - In culture, mature bovine ovarian oocytes were fertilized in vitro with freshly ejaculated ram spermatozoa treated with heparin. The zona pellucida does not prevent penetration of ram spermatozoa. The penetration rate varied between 10 and 84%, and in most instances, after 24 hr of culture, two normal-looking pronuclei and sperm tail were present in the cytoplasm. These results suggest that the zona pellucida of bovine oocytes does not represent a barrier for the penetration of ram spermatozoa. PMID- 2328128 TI - Changes in nuclear structure during eupyrene spermatogenesis in Murex brandaris. AB - Changes in nuclear structure during eupyrene spermatogenesis of Murex brandaris have been studied using light and electron microscopy. In the first phases, spermatogonia show round nuclei, with several electrodense masses of chromatin and a thin layer of heterochromatin associated with the nuclear membrane. Primary spermatocytes possess larger nucleii, with less condensed chromatin, and the synaptonemal complexes are apparent. During spermiogenesis, chromatin becomes lamellar, and the nucleus twists about its principal axis while it elongates. The nuclear twisting is accompanied by a progressive chromatin condensation, which causes a highly electrodense nucleus at the end of the process. PMID- 2328129 TI - Atypical spermatogenesis in Murex brandaris. AB - Atypical spermatogenesis in Murex brandaris occurs in specific areas of the testis. In the early stages, a large nucleus is apparent, together with highly electrodense drops of chromatin spread through the caryoplasm. Many mitochondria are observed at one point of the cytoplasm, and numerous centrioles appear. In the following stages, vacuolization and degeneration of the chromatin are apparent, producing half moon-shaped chromatinic bodies called "caryomerites." Some degeneration of the chondrioma occurs too. Later, the chromatin degenerates and the centrioles produce cilia, while the Golgi body, highly secretory at this stage, produces electrodense PAS- as well as Thiery-positive granules. Moreover, a vermiform-shaped anuclear ciliated cell with numerous electrodense cytoplasmic granules is observed in the M. brandaris atypical spermatozoon. PMID- 2328130 TI - Histochemical identification of primordial germ cells in diandric and digynic triploid mouse embryos. AB - Diandric and digynic triploid mouse embryos were isolated in the morning on day 10 of gestation. The embryos were separated from their extraembryonic membranes, and the latter were analysed cytogenetically by G-banding to establish the ploidy and sex chromosome constitution of these embryos. The diandric triploid embryos were produced by the technique of nuclear micromanipulation. Females were mated with male mice with a morphologically distinguishable "marker" chromosome to confirm the diandric status of these embryos. Digynic triploid and normal diploid embryos were isolated from LT/Sv strain females. These females spontaneously ovulate both primary and secondary oocytes, which are fertilisable and give rise to digynic triploid and normal diploid embryos, respectively. All the embryos were serially sectioned and processed in order to demonstrate the presence of alkaline phosphatase enzyme activity. This histochemical technique allowed primordial germ cells to be readily recognised, due to their characteristic location, cellular morphology, and staining appearance. Primordial germ cells were found in all the embryos studied, being located within the visceral yolk sac, at the base of the allantois, and/or in association with the wall or mesentery of the hindgut. The total number of germ cells present was established in nine diandric triploids and in five digynic triploids. The findings presented here represent the first demonstration that primordial germ cells can differentiate in either diandric or digynic triploid mammalian embryos. PMID- 2328131 TI - Modulation of mammalian sperm motility by quercetin. AB - The flavonoid quercetin inhibits collective motility of ejaculated ram spermatozoa in the first 2 hr of incubation; during the next 3-4 hr motility is stimulated. To explain this interesting effect, we followed the influence of quercetin on sperm glycolysis, extracellular pH, ATP content, mitochondrial respiration, and lipid peroxidation. The collective motility of untreated cells is decreased to about 40% of the original motility during two hours of incubation. During this time, the rate of glycolysis is constant, respiration rate is increasing, there is no change in ATP content, the rate of lipid peroxidation is very slow, and the extracellular pH became very acidic (pH 5.5). It is concluded that motility is decreased due to this acidification. This acidification is prevented to some extent by quercetin, which indirectly inhibits glycolysis. Quercetin inhibits motility due to the inhibition of the plasma membrane calcium pump, as we showed previously (Breitbart et al., J Biol Chem 260:11548-11553, 1985). The motility of untreated cells is arrested after 3.5 hr of incubation, whereas quercetin-treated cells show high motility, which continues for additional 2-3 hr. After 3.5 hr, the control cells show no glycolytic activity, ATP content and respiration rates are decreased, and rate of lipid peroxidation is highly increased. At this time, quercetin-treated cells show no glycolytic activity, only a small decrease in ATP content and respiratory rate, and a very low rate of lipid peroxidation. Based on these data it is concluded that sperm motility after 3.5 hr of incubation is dependent mainly on mitochondrial respiration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328132 TI - Prostaglandin levels in the rat resting gastric wall and enhancement of prostaglandin E2 generation after administration of mild hyperosmotic saline solution into the gastric lumen. AB - The PGE2 level in the rat resting stomach, dropped into liquid nitrogen after removal, was 44.6 +/- 8.3 ng/stomach, when determined by radioimmunoassay, but cutting of the greater curvature with scissors after removal caused an approximately sixfold increase in the PGE2 level. Compression of the stomach in situ with metal tongs refrigerated in liquid nitrogen markedly reduced the PG levels, and further purification by reversed-phase high performance liquid chromatography reduced the PGE2 and 6-keto-PGF1 alpha levels to 4.7 +/- 0.6 and 4.8 +/- 0.8 ng/stomach, respectively. Pretreatment of the rats with indomethacin (10 mg/kg, i.v.) did not decrease the PGE2 level, but the 6-keto-PGF1 alpha level was reduced slightly. The lowest level of PGE2 in the resting state was significantly increased after administration of 1.0 M NaCl solution into the gastric lumen. The peak value was 70.0 +/- 21.8 ng/stomach at 30 min, after which the level decreased gradually. The level of 6-keto-PGF1 alpha was not significantly increased during the administration of 1.0 M NaCl solution. PMID- 2328133 TI - Urinary thromboxane B2 and 2,3-dinor-thromboxane B2 in the neonate born at full term age. AB - We have developed a method for measurement of urinary 2,3-dinor-TXB2, which is a reflection of the actual rate of TXA2 synthesis by platelets in vivo. This determination was based on purification by high-pressure liquid chromatography and on measurement by RIA. After validation of the assay, we established the range of urinary Tx metabolites in healthy infants born at full-term during their first week of life. The 2,3-dinor-TXB2 levels were higher than in adults and declined gradually during the first seven days of life. PMID- 2328134 TI - Thromboxane in cardiovascular disease. PMID- 2328135 TI - [Flow in the entry chamber of the right ventricle: diastolic function indexes in a normal population]. AB - OBJECTIVES: To define normal values of indexes of diastolic function of right ventricle by bidimensional pulsed doppler echocardiography. STUDY DESIGN: Prospective study of normal individuals. MATERIALS AND METHODS: Thirty normal subjects by physical examination, electrocardiographic, radiological and echocardiographic criteria, aged between 22-48 (mean 31.2 +/- 6.7) were evaluated. We determined 16 different indexes and correlated them with heart rate, age and body surface; 27% of cases owing to the poor quality of records, were excluded. RESULTS: Eight indexes were heart rate dependent and for their use is necessary the respective correction; none of them correlated with age or body surface. Areas determined under the curves of flow are very time consuming and require great accuracy determination. So, we had correlated areas with other different indexes in order to obtain other parameters to give us the same information on a easier and quickly way. E/A relation correlated with all areas relations. CONCLUSIONS: The indexes determined can be considered as normal standard in order to evaluate, by a non-invasive way, right ventricle diastolic function. Nevertheless, the great proportion of records of poor quality is a limitation of the method. PMID- 2328136 TI - [Maximal values of serum creatine phosphokinase and its myocardial fraction in acute myocardial infarct. Correlation with a previous history of ischemic cardiopathy]. AB - OBJECTIVE: To evaluate the importance of preinfarction angina as a determinant of infarct size. DESIGN: Retrospective study of patients (pts) with acute myocardial infarction (AMI). SETTING: Patients admitted to an Intensive Care Unit of a University Hospital. PATIENTS: The study concerns 224 pts, 161 men women, aged 63.09 +/- 11.92 years, who did not receive thrombolytic or intravenous beta blocking therapy and in whom it was possible to establish the presence or absence, of previous ischemic heart disease. METHODS: Patients, were divided in 2 groups: A (1st AMI, 172 dts - 123 M, 49 F) and B (2nd AMI, 52 dts - 38 M, 14 F). These groups were subdivided according the presence of preinfarction angina (A1, B1) or its absence (A2, B2). The infarct size was evaluated by peak values of CK/CKMB. RESULTS: Group A: CK/CKMB--959/101; Group B: CK/CKMB--742/77 (p-NS). Subgroups--A1: CK/CKMB--1143/118; A2: CK/CKMB--725/78 (p less than 0.001); B1: CK/CKMB--635/59; B2: CK/CKMB--818/88 (p-NS). The analysis of CK/CKMB values distribution, according to the affected cardiac wall, has shown an identical correlation. CONCLUSION: 1--The larger infarct size in subgroup A1 (1st AMI without angina) suggests a protective effect by collateral circulation in subgroup A2 (1st AMI with angina). 2--The larger infarction (although not significantly) in group A (1st AMI), correlates with less viable muscle in group B (2nd AMI). 3--The higher values of CK/CKMB in group B2 (2nd AMI with angina) can be expected given the presence of residual ischemia. 4--The absence of the protective role by collateral circulation in patients of subgroup A1 (1st AMI without angina) suggests for them a stronger indication for thrombolytic therapy. PMID- 2328137 TI - [Inotropic reserve of the left ventricle in patients with chronic ischemic cardiopathy, studied using adrenaline stimulation. Prognostic significance]. AB - AIMS: To study by equilibrium radionuclide angiography (ERNA) the cardiac inotropic reserve after a myocardial infarction, and to evaluate its prognostic value. DESIGN: Patients in a chronic status of a myocardial infarction were studied by ERNA at a basal state and after stimulation with epinephrine, in the same session. Left ventricle (LV) functional abnormalities, global and regional, were evaluated. A 3-to-5 years follow-up was done. PATIENTS AND METHODS: Twenty five patients with a post myocardial infarction were included: 19 with an anterior infarction, 2 with an inferior and 4 with a combined one. All patients had LV dysfunction evaluated by Echocardiogram at hospital discharge. Global and regional LV function were studied by ERNA before and after inotropic stimulation, using increasing doses of epinephrine from 4.8 to 12 micrograms/minute. Heart rate and blood pressure were monitored. ERNA acquisition were done on left oblique best-septal and lateral views, over 400 cardiac cycles, using a Gama camera GE 400AC. Three groups of patients were considered, according with the change of LV global ejection fraction: increments greater than 2%--group A (positive response); changes between +2% and -2% - group B; decreases greater than 2%--group C (negative response). During a 3 to 5 years follow-up, the incidence of major cardiac events was analysed: cardiovascular mortality, angina, left ventricle failure, myocardial reinfarction and coronary artery by-pass graft surgery. RESULTS: LV global function-Inotropic stimulation was done with an average perfusion time of 30.8 minutes, with total doses of epinephrine between 176 and 660 ng. No significant changes of heart rate (5%) or blood pressure (5.3%) occurred. Basal LV global ejection fraction (EF) was 29.2%. Only 2 patients had a normal LV ejection fraction; 14 patients had a severe LV dysfunction (EF less than 30%) and 9 had a moderate reduction of ejection fraction (EF between 30% and 45%). From the 14 patients with EF less than 30%, twelve had an involvement of the LV anterior wall. After stimulation EF value ineditreased in 9 and decreased in one patient. From the 11 patients with EF greater than 30%, 6 experienced a increase of EF and 3 decreased of EF after stimulation. REGIONAL WALL MOTION: Group A--15 patients--75 segments. In this group 39 segments were related to necrotic ECG localization, and 79% of them contributed to EF increase after stimulation. Forty-one segments were not involved by necrosis, and 78% had a positive contribution to EF increase. Six patients had all LV segments contributing to the EF increase after stimulation. The other 9 patients, had 13 segments not responding to stimulation (EF increments greater than 2%): 5 of them were segments related to ECG site of infarction. Group B--6 patients--30 segments. Five patients had 9 segments with a positive contribution to EF after inotropic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2328139 TI - [Surgery of the coronary vessels in the elderly]. PMID- 2328138 TI - [Ruptured aneurysm of the sinus of Valsalva into the right ventricle--apropos of a case]. AB - A 37 year old man was referred to our institution because of a cardiac murmur, exertional dyspnea and fatigue, symptoms that began since 18 years of age. He reported a cardiac murmur since childhood, with no past history of rheumatic fever or infectious endocarditis. On clinic examination there was a systolic diastolic murmur louder in the third and fourth left intercostal space, just at the sternal left border. The 2 D-echo revealed a small disruption in the aorto septal continuity. Right heart catheterisation was performed, showing an increased pressure in the pulmonary artery and right ventricle; an increase in the oxygen saturation on the right heart chambers, suggested the presence of a left-to-right shunt, nevertheless the exact location of the defect was not possible to recognise. The study was complemented with Doppler color flow imaging that revealed a turbulent flow through the defect, with blood flowing from the aortic root into the right ventricular outflow tract. The diagnosis of ruptured aneurysm of sinus of Valsalva was made, being confirmed later by aortic angiography. A rare case is reported in which an aneurysm of the right coronary sinus ruptured into the right ventricle; we emphasize the important contribution of the Doppler color flow imaging to the correct diagnosis, technique rarely described in this type of complication. PMID- 2328141 TI - SequenceEditingAligner: a multiple sequence editor and aligner. AB - Here we present the SequenceEditingAligner system for editing multiple, aligned genetic sequences. This is an interactive multi-window color system that displays more than 3500 nucleotides or amino acids. The system handles nucleic acid or protein sequences with or without secondary structure data. More than 300 sequences, each more than 1500 elements in length, may be analyzed together. With the system scientists can classify elements, align sequences, edit them, find consensus patterns, and simultaneously generate oligomer frequency histograms and other statistics. PMID- 2328140 TI - Complexity charts can be used to map functional domains in DNA. AB - We measured local compositional complexity (LCC) of DNA sequences by calculating Shannon information content over mononucleotide frequencies. Eukaryotic DNA appeared to be "simpler" than bacterial DNA even at the level of short oligonucleotides. Moreover, different DNA functional domains displayed different compositional complexity in a systematic manner. In particular, the complexity of exon sequences was systematically higher than the complexity of corresponding introns. We therefore present examples of complexity charts (plots of complexity versus position in sequence) for pre-mRNA sequences from higher eukaryotes. By taking a window width of 100 nucleotides and a window step of 1 nucleotide, introns can be distinguished from exons in the majority of cases studied. Complexity charts of immunoglobulin variable regions allowed correct mapping of exons and introns in these sequences as well, a task that was impossible with commercial programs available to date. PMID- 2328142 TI - Comparison of the binding of 59Fe- and 239Pu-transferrin to rat liver cell membranes. AB - The binding of the 59Fe and 239Pu complexes of transferrin and 125I labelled transferrin [Tf (125I)] to isolated cell membranes of rat liver has been studied. Transferrin forms a complex with an integral protein of the membrane which has an apparent molecular weight of about 180 kDa and is stable only at pH 7.4. Iron-59 is eluted from Sephacryl S 300 columns together with Tf (125I) or the Tf-membrane protein complex while 239Pu seems to be bound to different membrane protein(s). After isolation of the Tf-binding protein from 35S-labelled membranes and incubation with one of the metal-Tf complexes 59Fe elutes from a Sephacryl S 300 column together with 35S at an apparent molecular weight of ca. 250 kDa while 239Pu is found in fractions of lower molecular weight. It is concluded from these results that there are Tf-receptors in the liver cell membrane to which iron transferrin may bind. Plutonium, however, seems to be dissociated from Tf and bound directly to other membrane proteins. PMID- 2328143 TI - Safety of late acetylcysteine treatment in paracetamol poisoning. AB - Twenty patients who had taken overdoses of paracetamol were treated with acetylcysteine between 12 and 24 hours after the incident. Although 19 patients had plasma paracetamol concentrations greater than those associated with a 90% risk of moderate to severe liver damage, this complication occurred in only seven (35%) individuals. No patient developed hepatic encephalopathy or acute renal failure and all recovered without sequelae. We conclude that acetylcysteine administration up to 24 hours following paracetamol overdose is not dangerous and may prevent further liver damage. PMID- 2328145 TI - Human toxicology and the British Toxicology Society--a closer association. PMID- 2328144 TI - Effect of occupational lead exposure on serum 1,25-dihydroxyvitamin D levels. AB - The effects of lead exposure on serum 1,25-dihydroxyvitamin D levels and calcium homeostasis have been studied in 63 males occupationally exposed to the metal in the UK. The exposure indices used were blood lead, reflecting short-term exposure, and an in vivo X-ray fluorescence measurement of tibia lead which reflects cumulative lead exposure. Serum 1,25-dihydroxyvitamin D levels were higher than those in a referent population, who were non-occupationally exposed to lead, and were correlated with both blood lead and tibia lead. Multiple regression analysis suggested that blood lead was the variable responsible for the increase in serum 1,25-dihydroxyvitamin D. There were no other abnormalities in calcium metabolism associated with the degree of lead exposure. PMID- 2328146 TI - The British Toxicology Society and the New Journal. PMID- 2328147 TI - Post-mortem serum concentration of cantharidin in a fatal case of cantharides poisoning. AB - A patient admitted to hospital died shortly after admission without a proper diagnosis having been made. Symptoms as well as the presence of a brown powder found in the possession of the deceased indicated the possibility of cantharidin intoxication. Cantharidin was positively identified by means of a GC/MS analysis, utilizing the selected ion monitoring technique (SIM), for m/z = 197.0813, (M + H+) for cantharidin, under positive chemical ionization conditions at a resolution of 7000 and a mass window of 30 ppm. Quantitation was done by means of a GC/MS SIM analysis of a toluene extract of acidified post-mortem serum under El+ conditions at a resolution of 3000, using clofibrate as internal standard and monitoring m/z = 128.0473 and 128.0029 for cantharidin and clofibrate respectively. The post-mortem serum was found to contain cantharidin at a concentration of 72.3 ng/ml whilst the cantharides powder contained 0.87% cantharidin. PMID- 2328148 TI - Human metabolism of arsenobetaine ingested with fish. AB - 1. Six volunteers ingested 74As-labelled arsenobetaine with a fish meal. The retention and distribution of the tracer were studied by body radioactivity measurements. 2. The tracer became rapidly dispersed in soft tissues, with no major concentration in any localized organ or region. 3. In all subjects less than 1% of the ingested activity remained in the body after 24 days. 4. Any losses from the skin were minor in relation to those by other routes of excretion. PMID- 2328149 TI - Thrombocytopenia associated with thallium poisoning. PMID- 2328150 TI - A case of unusual suicidal poisoning by the organophosphorus insecticide dimethoate. AB - A 20-year-old male who attempted suicide by injecting subcutaneously 10 ml of Sistemin 40 (40% dimethoate) was admitted 16 h later. General weakness, muscular fibrillations and a marked inhibition of red blood cell and serum cholinesterases were the prominent signs of intoxication. The antidotal treatment of intermittent boluses of atropine, oxime HI-6 and diazepam was combined with symptomatic therapy. Cholinesterase activity decreased within the next 3 d. In contrast to the marked general improvement of the patient, the return of cholinesterase activities was very slow. The patient was discharged 24 d after the poisoning with no notable consequences which could be ascribed to the intoxication. PMID- 2328151 TI - Toxicokinetics of paraquat in humans. AB - 1. The toxicokinetics of paraquat were studied in 18 cases of acute human poisoning using a specific radioimmunoassay. Plasma paraquat concentration exhibited a mean distribution half-life (t1/2 alpha) of 5 h and a mean elimination half-life (t1/2 beta) of 84 h. Cardiovascular collapse supervened early during the course of the intoxication and was associated with the distribution phase. Death related to pulmonary fibrosis occurred late and was associated with the elimination phase. 2. Pharmacokinetic analysis of urine paraquat excretion confirmed the biphasic decline of paraquat. Moreover, renal paraquat and creatinine clearances were not correlated but renal paraquat clearance was never higher than the renal creatinine clearance. 3. Tissue paraquat distribution was ubiquitous with an apparent volume of distribution ranging from 1.2 to 1.6 l/kg. Muscle could represent an important reservoir explaining the long persistence of paraquat in plasma and urine for several weeks or months after poisoning. PMID- 2328152 TI - Strength of meaning--strong words and a certain message? AB - The ability to convey specific meanings is important to scientists in their writing. However, difficulties arise when the ideas to be portrayed are judgmental. While extreme terms expressing strength of meaning are readily understood, more subtle ones appear not to be. PMID- 2328153 TI - Accidental poisoning with podophyllin. AB - Podophyllin is available without prescription and is commonly used in the topical treatment of warts. We describe a case of accidental ingestion of podophyllin, mistaken for cough linctus, and its resultant toxicity. PMID- 2328154 TI - Crotamiton overdose. PMID- 2328155 TI - Diagnosis by PCR of HIV-1 infection in seronegative individuals at risk. PMID- 2328156 TI - Retroviral vectors expressing soluble CD4: a potential gene therapy for AIDS. AB - Retroviral vectors have been developed which produce a secreted form of the helper/inducer T-cell antigen, CD4. Amphotropically packaged vectors were used to transduce cells, and these cells were shown to express the secreted CD4 (sCD4) gene product. The sCD4 produced by the viral vectors is immunoprecipitated by monoclonal antibodies against CD4, which specifically block human immunodeficiency virus (HIV) infection of helper/inducer T cells. A direct physical interaction of vector-produced sCD4 and HIV-1 gp120 was demonstrated by coprecipitation of sCD4/gp120 with antiserum directed against HIV gp120. Furthermore, transduced cells producing sCD4 can protect HIV-susceptible cells from infection by HIV. These data suggest that gene therapy is a potential approach for the treatment of AIDS. PMID- 2328157 TI - Selective killing of HIV-infected cells by anti-gp120 immunotoxins. AB - Either ricin A chain (RAC) or Pseudomonas exotoxin (PE) was conjugated with a murine monoclonal antibody (0.5 beta) directed against an external envelope glycoprotein (gp120) of human immunodeficiency virus (HIV). Effects of the immunotoxins produced against infected cells were evaluated. Selective inhibition of the proliferation and killing of chronically HIV infected cells were observed in the presence of the immunotoxins. To determine the feasibility of the immunotoxins against the infected cells in seropositive subjects, we attempted to detect gp120-bearing cells in peripheral blood mononuclear cells (PBM) by cytofluorography. Cells in the monocyte/macrophage region of 2 of 10 PBM samples from HIV-infected individuals were found to react with 0.5 beta (18.1% and 12.8%). Furthermore, the cell population which was reactive with 0.5 beta was also susceptible to RAC conjugated with 0.5 beta. These results suggest that the strategy of using anti-gp120 immunotoxin to eliminate HIV-infected cells may be feasible in infected individuals. PMID- 2328159 TI - Behavioral and pharmacological treatment of persistent urinary incontinence in the elderly. AB - Research has demonstrated that behavioral interventions can help to decrease or eliminate urinary incontinence. Pharmacological agents have also been shown to be effective in the management of this problem. This article describes simple low risk behavioral techniques and pharmacological approaches that can be used by nurse practitioners to assist their incontinent patients to control this embarrassing and expensive problem. PMID- 2328158 TI - 3'-Azido-2',3'-dideoxyuridine (AzddU): comparative pharmacokinetics with 3'-azido 3'-deoxythymidine (AZT) in monkeys. AB - The pharmacokinetics of the anti-human immunodeficiency virus type 1 nucleosides, 3'-azido-2',3'-dideoxyuridine (AzddU) and 3'-azido-3'-deoxythymidine (AZT) were characterized in rhesus monkeys. Half-life, total clearance, and steady-state volume of distribution were similar for both compounds. The observed pharmacokinetic parameters for AZT were comparable to those previously reported in humans. Oral absorption of AzddU and AZT was virtually complete after 60 mg/kg. However, bioavailability of both nucleosides was markedly lower (less than 50%) after 200 mg/kg, possibly indicating the involvement of a saturable absorption mechanism. The nucleosides were also well absorbed after subcutaneous administration. AzddU and AZT penetrated the cerebrospinal fluid (CSF) with concentration ratios in CSF:serum ranging from 0.05 to 0.25 one hour after drug administration. The glucuronides of AZT and AzddU were readily detected in urine. Hemogram and blood chemistry values for animals receiving short-term treatment (3 doses) with either AZT or AzddU did not exhibit any significant changes when compared with untreated control monkeys. The similar pharmacokinetic characteristics of AzddU compared with AZT suggest that clinical trials of AzddU are warranted. PMID- 2328160 TI - The nurse practitioner and clinical nurse specialist: should the roles be merged? PMID- 2328161 TI - Radon: implications for the health professional. AB - Radon is a colorless, odorless gas formed by radioactive decay of radium and uranium, which are naturally present in the earth's crust. When concentrated indoors, this invisible gas becomes a potential health hazard. The Environmental Protection Agency estimates that up to 20,000 lung cancer deaths annually can be attributed to prolonged radon exposure. Radon is an important health issue that should be understood by all health care professionals. This paper discusses some of the important issues regarding radon, such as the incidences of lung cancer believed to be attributable to radon, the high-risk areas in the United States, federal safety guidelines, and public apathy. These issues and their impact on the health care required by professionals, especially nurse practitioners, are discussed. PMID- 2328162 TI - Nurse practitioner intervention to improve postpartum appointment keeping in an outpatient family planning clinic. AB - A nurse practitioner (NP) program to improve postpartum appointment keeping in an outpatient family planning clinic is described and evaluated. The subjects (N = 59) were non-high-risk obstetric patients prescheduled to be seen at 6 weeks postpartum by the NP. Two groups were identified by convenience sampling: Group A (n = 25), the nonintervention group, and Group B (n = 34), the intervention group. Two types of intervention were used: a postpartum telephone call after discharge (n = 11), or a predischarge postpartum visit (n = 23). Results suggest that those in the intervention group were more likely to keep their appointments (p less than .02); only the postpartum visit increased the probability of appointment keeping (p less than .05). PMID- 2328163 TI - Nurse practitioners and Physician Payment Review. PMID- 2328164 TI - See your physician. Marketing and management. PMID- 2328165 TI - Identification of a high risk subgroup of patients with silent ischaemia after myocardial infarction: a group for early therapeutic revascularisation? AB - Asymptomatic ("silent") ischaemia has been shown to be of prognostic significance in patients with stable and unstable angina and more recently in patients recovering after myocardial infarction. No therapeutic regimen has yet been shown to improve the prognosis of patients with silent ischaemia after infarction, which can be found in as many as a third of these patients. Attempts to achieve therapeutic revascularisation in all these patients may be undesirable, but early revascularisation could be especially beneficial in some selected high risk patients. Two hundred and fifty consecutive clinically stable survivors of myocardial infarction who had predischarge submaximal exercise tests were followed up for a year. Silent ischaemia was found in 27% of these patients; 15% had symptomatic ischaemia. Patients with a positive exercise test were prescribed a beta blocker before discharge. Mortality in patients with silent (9.4%) and symptomatic (5.4%) ischaemia in the first year after infarction was not significantly different. Patients with symptomatic ischaemia were more likely to have undergone coronary artery bypass grafting in the first year. Patients with silent ischaemia were, however, significantly more likely to die than patients with a negative exercise test (relative odds 12:1). Patients with silent ischaemia and an abnormal blood pressure response or who could not complete a submaximal exercise protocol were at particularly high risk, being 32 times more likely to die than those with a negative test (95% confidence interval from 3.3 to 307 times more likely). First year mortality in this group was 22%. The benefits of therapeutic revascularisation in this high risk group need to be studied. PMID- 2328166 TI - Non Q wave infarction: exercise test characteristics, coronary anatomy, and prognosis. AB - The exercise test characteristics, coronary anatomy, and prognosis of patients discharged after non Q wave myocardial infarction were compared with those in whom Q wave infarction occurred. Of the 339 patients studied, all of whom were less than or equal to 70 years, 87 (26%) had had a non Q wave infarction. There were no significant differences in the exercise test characteristics between the two groups, and in those 149 patients in whom angiography was performed triple vessel disease was present in 36/114 (32%) of the Q wave group and 9/35 (26%) of the non Q wave group. The infarct related artery was more often patent in the non Q wave group (27/35 (77%] than in the Q wave group (53/114 (46%]. The one year mortality and the reinfarction and angina rates were similar in the two groups and the exercise test remained a good discriminator for predicting patients at risk of future cardiac events in both groups. In view of the similar outcome and severity of coronary disease in those aged less than or equal to 70 with non Q wave infarcts, the distinction between Q and non Q wave infarction need not influence management decisions in patients after myocardial infarction. PMID- 2328167 TI - Familial ventricular tachycardia: a report of four families. AB - Four cases of familial ventricular tachycardia are presented. In each family the proband was an adolescent girl. Twelve members in the four families were affected and all were female. The clinical and electrocardiographic features were relatively constant within each family but there were striking differences between families. These differences argue against a common electrophysiological or pathophysiological basis for the ventricular tachycardia. PMID- 2328168 TI - Echocardiographic appearance of pulmonary artery stenosis. AB - Colour flow Doppler mapping can show abnormalities of flow even when the echocardiographic image is equivocal. Routine echocardiography in two patients who were thought to have pulmonary valve stenosis and a ventricular septal defect initially appeared to be normal. Colour flow Doppler mapping, however, showed multiple flow aliasing within the pulmonary artery, approximately 1.5 cm downstream from the pulmonary valve. More detailed examination by cross sectional echocardiography showed a membrane at this level in both patients. It is possible that more cases of this uncommon anomaly will come to light with increasing use of Doppler techniques. PMID- 2328169 TI - Percutaneous transluminal coronary angioplasty with cardiopulmonary bypass for stenosis of the most proximal part of the left anterior descending coronary artery. AB - An 85 year old man with unstable angina pectoris was treated successfully with percutaneous transluminal coronary angioplasty supported by cardiopulmonary bypass and intra-aortic balloon pumping. Coronary angiography had shown stenoses in both the left main stem and left anterior descending coronary arteries. Drug treatment had been ineffective and he was too old for coronary arterial bypass grafting. PMID- 2328170 TI - Origin of the left coronary artery from the right pulmonary artery and ventricular septal defect in a child of a mother with raised plasma phenylalanine concentrations throughout pregnancy. AB - A child with anomalous origin of the left coronary artery from the right pulmonary artery, ventricular septal defect, fetal growth retardation, and facial abnormalities was born to a woman in whom plasma phenylalanine concentrations had been raised throughout pregnancy. The cardiac abnormalities were diagnosed by angiography when the child was eight months old. The anomalous coronary artery was imaged in a subsequent echocardiogram. Development retardation was caused by maternal phenylketonuria, which may also have been responsible for the development of the ventricular septal defect and the coronary anomaly. If dietary treatment of the mother had been started before pregnancy damage to the child might have been prevented. PMID- 2328172 TI - Pulmonary oedema with shock induced by hydrochlorothiazide: a rare side effect mimicking myocardial infarction. AB - The case of a 68 year old man in whom hydrochlorothiazide induced pulmonary oedema with hypovolaemic shock is presented. The condition was misdiagnosed as myocardial infarction until an early echocardiogram excluded a cardiac cause. The diagnosis was confirmed by an oral challenge. PMID- 2328171 TI - Thrombosed saccular aneurysm of a sinus of Valsalva: unusual cause of a mediastinal mass. AB - A 33 year old man presented with a short history of slight fever and chest pain that was worse on inspiration. An electrocardiogram was consistent with pericarditis. Chest radiography, echocardiography, and computed tomography suggested the presence of a mediastinal tumour. At operation the mass was found to be attached to the right sinus of Valsalva and proved to be a large saccular aneurysm full of laminated thrombus. PMID- 2328173 TI - Absence of the aortic valve cusps with mitral atresia, normal left ventricle, and intact ventricular septum. AB - A case of a previously unreported anomaly is presented in which absence of the aortic valve cusps, mitral atresia, a normal left ventricle, and an intact ventricular septum were diagnosed by cross sectional echocardiography. The development of a normal left ventricle, rather than the hypoplastic ventricle usually associated with mitral atresia, is explained by filling of the ventricular cavity via the regurgitant aortic valve. PMID- 2328176 TI - Prediction of infusion rates: computer study. AB - The administration of two test doses in the ratio 1:0.5 has been shown to provide sufficient data (time intervals) to predict the infusion rate necessary to maintain the concentration of a drug at the therapeutic threshold in a two compartment pharmacokinetic model. If the relationship between the durations of action of the test doses is linear, only one test dose may be needed to predict the infusion rate. PMID- 2328174 TI - Postoperative hypoxaemia: comparison of extradural, i.m. and patient-controlled opioid analgesia. AB - Arterial oxygen saturation (SaO2) was analysed continuously before and for 24 h after lower abdominal surgery in 30 patients breathing air using one of three postoperative analgesic regimens: i.v. diamorphine using a patient-controlled analgesia system (PCAS), extradural diamorphine or i.m. morphine. Hypoxaemia was defined as SaO2 less than 94% for more than 6 min h-1. Before operation there was no difference between the three analgesia groups assessed by the duration when SaO2 was less than 94%. After operation the pattern of SaO2 vs time distribution was either stable, with little variation from hour to hour with no hypoxaemia, or unstable with large variation with 30% of patients hypoxaemic. Thus three patterns of SaO2 distribution were seen in the postoperative period: stable without hypoxaemia (4/10 PCAS, 0/10 extradural, and 1/10 i.m. patients), unstable without hypoxaemia (4/10 PCAS, 5/10 extradural and 7/10 i.m. patients) and unstable with prolonged nocturnal periods with SaO2 less than 94% for a mean of 17.7 min h-1, 95% confidence limits (CL) 10-25 min h-1, (2/10 PCAS, 2/10 i.m. and 5/10 extradural patients). Before operation, the unstable group with hypoxaemia spent longer at less than 94% SaO2 (mean 4.8 min h-1, 95% CL 1.0-8.6 min h-1) than the stable group (mean 0.4 min h-1, 95% CL 0.17-0.61 min h-1) and this was a predictor of postoperative hypoxaemia. Hypoxaemia occurred in all analgesia groups, but extradural diamorphine tended to cause longer periods. Some patients at risk of postoperative hypoxaemia may be predicted by preoperative monitoring of SaO2 although extradural diamorphine boluses were associated with hypoxaemia in patients with normal preoperative values. PMID- 2328175 TI - Buprenorphine disposition in patients with renal impairment: single and continuous dosing, with special reference to metabolites. AB - The disposition of buprenorphine has been studied in two patient groups to assess the influence of impaired renal function on the metabolism of buprenorphine and two of its metabolites, buprenorphine-3-glucuronide (B3G) and norbuprenorphine (NorB). A single i.v. dose of 0.3 mg was given to 15 patients (nine with dialysis dependent renal failure) undergoing lower abdominal or peripheral body surface surgery. Blood was sampled up to 24 h. Concentrations of buprenorphine, B3G and NorB were assayed by a differential radioimmunoassay technique. There were no differences in buprenorphine kinetics between anaesthetized healthy patients and those with renal impairment: mean elimination half-lives 398 and 239 min; clearance 651 and 988 ml min-1; apparent volume of distribution at steady state 313 and 201 litre, respectively. Both metabolites were undetectable following the single i.v. dose. In a second group of 20 patients (eight with renal impairment), buprenorphine was administered by continuous infusion for provision of analgesia and control of ventilation in the ITU (median infusion rate 161 micrograms h-1 (range 36-230 micrograms h-1) for a median duration of 30 h (2-565 h). Buprenorphine clearance in patients with normal and impaired renal function was similar (934 and 1102 ml min-1, respectively), as were dose-corrected plasma concentrations of buprenorphine. In patients with renal failure, plasma concentrations of NorB were increased by a median of four times, and B3G concentrations by a median of 15 times. PMID- 2328177 TI - Comparison of neuromuscular block in the diaphragm and hand after administration of tubocurarine, pancuronium and alcuronium. AB - The onset and offset of neuromuscular block in the diaphragm and in the adductor pollicis muscle were recorded using unilateral supramaximal stimulation of phrenic and ulnar nerves. Thirty patients were allocated randomly to receive tubocurarine 0.4-0.5 mg kg-1, pancuronium 0.07-0.08 mg kg-1 or alcuronium 0.2-0.3 mg kg-1. In all cases the onset of neuromuscular block occurred in the diaphragm before adductor pollicis, and spontaneous recovery was evident first in the diaphragm. There was a correlation between the time of spontaneous reappearance of twitch in the diaphragm and in the adductor pollicis only in the patients who received pancuronium (r = 0.97, P less than 0.05 for reappearance of the first twitch of the train-of-four of each muscle). The duration of paralysis in the diaphragm was less than 5 min in five patients who received tubocurarine and in one who received alcuronium; this corresponded to a period of paralysis in the adductor pollicis muscle of more than 25 min in each case. PMID- 2328179 TI - Relationship between lower oesophageal contractility and type of surgical stimulation. AB - We have studied the effects of two discrete types of surgical stimulation on contractions in the lower oesophagus. Forty-four female patients undergoing either abdominal hysterectomy or varicose vein surgery were anaesthetized using a standard technique. The frequency of spontaneous oesophageal contractions (SLOC) and amplitude of provoked contractions (PLOC) were greater in those patients undergoing hysterectomy. The oesophageal index (OCI), a single index combining both types of contractions, was found also to relate to the nature of the surgical stimulus. PMID- 2328178 TI - Edrophonium antagonism of atracurium during enflurane anaesthesia. AB - To determine the influence of enflurane on the ability of edrophonium to antagonize atracurium block, dose-response curves were constructed for edrophonium in the presence of 0%, 1% and 2% enflurane, and for 2% enflurane discontinued at the time of administration of edrophonium. One hundred ASA Physical Status I or II patients (four groups of 25), selected randomly and undergoing elective surgery, received atracurium 0.5 mg kg-1, with thiopentone, nitrous oxide and enflurane. Supplementary doses of fentanyl were given if needed. Train-of-four (TOF) stimulation was applied every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When first twitch height (T1) had recovered spontaneously to 10% of initial value, edrophonium 0.1, 0.2, 0.4 or 1 mg kg-1 was administered by random allocation. Enflurane concentrations remained constant, except that enflurane was discontinued in 50% of the patients who had received 2% enflurane. Monitoring was continued for at least 10 min, at which time T1 and TOF ratio (T4/T1) were measured. The ED80 for T1 recovery depended on the dose of enflurane: 0.08 (SEM 0.03), 0.21 (0.06) and 0.42 (0.18) mg kg-1 for 0%, 1% and 2% enflurane, respectively (P less than 0.005). With enflurane 2% discontinued, the ED80 was 0.095 (0.050) mg kg-1 (P less than 0.02 compared with 2% enflurane).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328180 TI - Validation of a system for measurement of metabolic gas exchange during anaesthesia with controlled ventilation in an oxygen consuming lung model. AB - An oxygen consuming lung model was used for evaluation and validation of a technique for metabolic gas exchange measurements during controlled ventilation. The technique comprised a Servo 900 C ventilator (Siemens) and separate oxygen and carbon dioxide analysers (Beckman). Measurements of oxygen consumption and carbon dioxide production were made either by measuring inspired and expired ventilation and gas fractions in these volumes or by measuring gas fractions and calculating expired ventilation from inspired by transformation (Haldane). Irrespective of the FIO2, measured values correlated well with lung model settings: measured values were within +/- 2% of simulated. When Haldane transformation was used with an FIO2 of 0.5 there was a significant underestimation of oxygen consumption. Carbon dioxide production values correlated well irrespective of the FIO2 used or method of measurement of ventilation volume. Metabolic gas exchange measurements by measuring both inspired and expired ventilation volumes may be used when inert gases are not in equilibrium, for example during nitrous oxide anaesthesia. PMID- 2328181 TI - Estimation of left ventricular volume and ejection fraction by two-dimensional transoesophageal echocardiography: comparison of short axis imaging and simultaneous radionuclide angiography. AB - We have compared short axis images of the left ventricle (LV) obtained with transoesophageal echocardiography (TOE) to assess LV size and function with those obtained by radionuclide angiography (RNA). Simultaneous TOE and RNA images were attempted in 14 patients and results obtained in 12 patients undergoing repair of abdominal aortic aneurysms. The area of the LV cavity seen in the short axis images at a mid-papillary muscle level at end-systole (ESA) and end-diastole (EDA) were compared with volumes measured by RNA at end-systole (ESV) and end diastole (EDV). An area ejection fraction (AEF) calculated from the TOE images (AEF = EDA-ESA/EDA) was compared with the RNA ejection fraction (EF) where EF = EDV-ESV/EDV. Good correlations were found between TOE log EDA and RNA log EDV (r = 0.86), TOE log ESA and RNA log ESV (r = 0.92) and TOE AEF and RNA EF (r = 0.96). This suggests that TOE short axis imaging at a mid-papillary muscle level is generally adequate for monitoring LV function during operation. PMID- 2328182 TI - Memory function after i.v. midazolam or inhalation of isoflurane for sedation during dental surgery. AB - Memory function was assessed with a recognition memory test in 40 dental patients before and after sedation with i.v. midazolam or inhalation of isoflurane. The two groups were comparable, but there was a significant impairment of memory (P less than 0.001) at the time of discharge for both words and faces after midazolam, but not after isoflurane. PMID- 2328183 TI - Cytosolic free calcium concentrations in lymphocytes from malignant hyperthermia susceptible patients. AB - Halothane in concentrations exceeding 1.2 mmol litre-1 increased (P less than 0.05) the apparent intracellular concentration of calcium in lymphocytes from 12 patients being tested for susceptibility to malignant hyperthermia (MH) using the fluorescent Ca2+ indicator, fura2. There was no difference in [Ca2+]i between lymphocytes from patients found to be MH susceptible (n = 5) on in vitro contracture testing with halothane and caffeine and those from MH negative patients (n = 6). Thus determination of [Ca2+]i in lymphocytes after exposure to halothane could not be used as a diagnostic test for MH susceptibility. PMID- 2328184 TI - Halothane hepatitis: a case report. AB - This report describes a patient who required 12 anaesthetics over a period of 25 yr. Halothane was used on at least five occasions. The first documented halothane anaesthetic was followed by jaundice. Subsequently, he received at least four halothane anaesthetics, all of which were followed by illness attributable possibly to hepatotoxicity. He also received five nonhalothane anaesthetics, none of which was followed by postoperative illness. This case history shows strong evidence of halothane causing hepatotoxicity. It also shows an inverse relationship between the severity of the disease and the interval between halothane exposures. It is presented as evidence in favour of the advice on using halothane issued by the Committee on Safety of Medicines. PMID- 2328185 TI - Extradural anaesthesia for caesarean section in achondroplasia. AB - We describe the successful management of a 26-yr-old achondroplastic dwarf undergoing elective Caesarean section under extradural anaesthesia. The patient had marked thoracolumbar kyphoscoliosis and clinical features which suggested that tracheal intubation would prove difficult. Block sufficient for surgery required only 5 ml of 0.5% bupivacaine and, apart from an initial unilateral block and mild intraoperative hypotension, her perioperative course was uneventful. PMID- 2328186 TI - Use of regional anaesthesia in a patient with acute porphyria. AB - The porphyrias are inherited disorders of haem metabolism, acute attacks of which may be precipitated by anaesthesia, surgery and pregnancy. The principal clinical feature of the disease is an acute neuropathy. A patient with acute intermittent porphyria was given bupivacaine as part of a regional anaesthetic for Caesarean section. The course of anaesthesia was uneventful. PMID- 2328187 TI - Proceedings of the Anaesthetic Research Society. London, November 10-11, 1989. Abstracts. PMID- 2328188 TI - Anaesthesia and outcome of surgery for fractured neck of femur. PMID- 2328189 TI - Use of a magnet with programmable pacemakers. PMID- 2328190 TI - Rapid screening for polymorphisms in dextromethorphan and mephenytoin metabolism. AB - 1. The phenotyping parameters for dextromethorphan and mephenytoin were assessed in 48 normal male volunteers following administration of each metabolic probe drug on separate occasions and together according to a randomized 3-way crossover design. 2. Neither the urinary S-/R-mephenytoin ratio nor the dextromethorphan metabolic ratio were altered significantly by coadministration of the probe drugs. 3. Five-hundred and nineteen subjects were screened for expression of mephenytoin 4-hydroxylase and dextromethorphan O-demethylase activity following the coadministration of mephenytoin and dextromethorphan. The activity was determined in each case by methods not requiring any quantitative measurements. 4. Nineteen (3.7%) of the subjects were identified as poor metabolizers (PMs) of mephenytoin and 35 subjects (6.7%) as PMs of dextromethorphan. 5. All PMs of dextromethorphan were confirmed by more rigorous evaluation of the metabolic ratio. PMID- 2328191 TI - The effect of multiple dosage on the kinetics of glucuronidation and sulphation of diflunisal in man. AB - 1. The single (250 and 500 mg) and multiple dose (250 and 500 mg twice daily for 15 days) pharmacokinetics of diflunisal were compared in young volunteers. 2. The plasma clearance of diflunisal was lowered significantly after multiple dose administration (5.2 +/- 1.2 and 4.2 +/- 0.7 ml min-1 for the 250 and 500 mg twice daily regimens, respectively) as compared with single dose administration 11.4 +/ 3.1 and 9.9 +/- 2.0 ml min-1 for the 250 and 500 mg single doses, respectively). 3. The partial metabolic clearances of diflunisal by acyl and phenolic glucuronide formation were lowered significantly (greater than 50%) after multiple dose administration. 4. The urinary recovery of diflunisal sulphate increased as a function of dose: 6.1 +/- 2.8 and 9.1 +/- 3.5% following the 250 and 500 mg single dose, respectively, and 10.9 +/- 3.1 and 15.9 +/- 3.6% following the 250 and 500 mg twice daily regimens. The partial metabolic clearance of diflunisal by sulphate conjugation was unchanged following multiple dose administration. 5. The plasma protein binding of diflunisal was concentration-dependent. Analysis of unbound plasma clearances of diflunisal showed that its total plasma clearance following 500 mg twice daily was affected by both saturable glucuronidation and concentration-dependent plasma binding. PMID- 2328192 TI - Plasma and urine aluminium concentrations in healthy subjects after administration of sucralfate. AB - 1. Sucralfate (basic sucrose aluminium sulphate), a topical intestinal agent, was administered in suspension or granule form to 25 healthy subjects at a total dose of 4 g day-1 for 21 days. Aluminium in plasma and 24 h urine samples was assayed before, during and after administration of sucralfate by inductively coupled plasma optical emission spectrometry. 2. Sucralfate produced significant increases in plasma and urine aluminium concentrations. On average, plasma aluminium increased from about 2 micrograms 1-1 to more than 5 micrograms 1-1 and 24 h urine aluminium increased from less than 5 micrograms to more than 30 micrograms. Both plasma and urine aluminium concentrations decreased rapidly after sucralfate was stopped. However, urinary aluminium concentrations remained higher than normal 5 and 10 days after discontinuation of sucralfate administration. Moreover subjects receiving sucralfate granules had significantly higher average urinary excretion of aluminium than subjects receiving the suspension. 3. The small but significant increase in plasma and urine aluminium following sucralfate administration in therapeutic doses may reflect intestinal absorption of aluminium. Although such absorption would appear to be moderate in healthy subjects, it is suggested that aluminium-based treatments should be used only intermittently, especially in patients with renal disorders. PMID- 2328193 TI - The pharmacokinetics of oral indoramin during pregnancy. AB - 1. The pharmacokinetics of indoramin (Baratol; Wyeth) and its active metabolite 6 hydroxyindoramin administered to 13 women as a single 37.5 mg dose of indoramin were compared under pregnant and post-partum conditions. 2. No significant differences were observed between values determined under pregnant and post partum conditions, for any pharmacokinetic parameter. Cmax and AUC values in individual subjects differed, in most cases, by no more than two-fold, i.e. the same order of magnitude as intra-subject variation seen in volunteers dosed repeatedly with indoramin. 3. Median values of Cmax, AUC(0.24) and t 1/2,z were of a similar order to values seen previously in normal volunteers after a single 37.5 mg dose. 4. It is concluded that in treating hypertension associated with pregnancy, this study does not provide evidence to depart from the usual clinical practice of titrating indoramin dosage with control of blood pressure as the end point, keeping in mind the restriction of the dose-limiting side-effect of sedation. PMID- 2328194 TI - Effect of intermittent administration of omeprazole on serum pepsinogens in duodenal ulcer patients and healthy volunteers. AB - 1. Omeprazole, a substituted benzimidazole inhibitor of the gastric H+/K(+)-APT ase, was administered orally at a dose of 20 mg in the morning of 3 consecutive days, followed by a period of 4 days without medication, and this intermittent dosage regimen was continued for 4 weeks. 2. During intermittent administration of omeprazole to 10 patients with duodenal ulcer disease and 10 healthy volunteers concentrations of serum pepsinogen A and serum pepsinogen C were monitored by sensitive and specific radioimmunoassays to study whether the effect of this treatment on serum pepsinogens is different between patients and normal subjects and to evaluate whether serum pepsinogen levels can be used to assess compliance with therapy. 3. Administration of omeprazole for 3 days induced significant increases in pepsinogen A and pepsinogen C serum concentrations, which rapidly fell after stopping the omeprazole intake. The pattern of serum pepsinogens after stopping the drug was different for duodenal ulcer patients and normal subjects. Both pepsinogens were intra-individually related in both patients and healthy subjects when compared during the first and last 3-day course with omeprazole, but in duodenal ulcer patients both pepsinogens tended to be higher in the last treatment course, while the opposite was found in the normal subjects. 4. The present study confirms that serum pepsinogen concentrations are higher in duodenal ulcer patients than in normal subjects, but also shows for the first time that serum pepsinogens in the patients respond differently upon stimulation with omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328195 TI - Clofibrate raises human 24 h intragastric acidity but does not affect plasma gastrin concentration. AB - 1. We studied the effects of acute oral dosing with clofibrate (500 mg four times daily) on 24 h intragastric acidity and plasma gastrin concentration in 12 healthy female subjects. 2. The 24 h integrated intragastric acidity rose from 429 mmol l-1 h (95% CI 296-479) before dosing to 527 mmol l-1 h (95% CI 385-664) on the day of dosing (+23%; P = 0.041), but no change was observed in the 24 h integrated plasma gastrin concentration: 420 pmol l-1 h (95% CI 282-499) before and 389 pmol l-1 h (95% CI 249-489) during dosing (P = 0.182). 3. We conclude that clofibrate has no acute antisecretory effect on the human stomach, and that human gastrin-induced enterochromaffin-like cell proliferation is unlikely with this drug. PMID- 2328196 TI - The toxicity of amodiaquine and its principal metabolites towards mononuclear leucocytes and granulocyte/monocyte colony forming units. AB - The cytotoxicity of amodiaquine (AQ), amodiaquine quinoneimine (AQQI) and desethylamodiaquine (AQm) has been assessed in comparison with that of chloroquine (CQ) using mononuclear leucocytes (MNL) and granulocyte/monocyte colony forming units (GM-CFU) from haematologically normal subjects. Toxicity toward MNL was assessed after 2 h and 16 h incubations with each compound. After 2 h, AQ, AQm and AQQI but not CQ (within the concentration range 1-100 mumols l 1) produced a significant decrease in cell viability. After 16 h, all four compounds significantly increased cell death. After both 2 h and 16 h incubations CQ was the least toxic and AQQI the most toxic of the four compounds towards MNL. Toxicity to GM-CFU was assessed by the inhibition of colony formation in vitro. After 10-14 days incubation, there was significant concentration-dependent inhibition of colony formation by AQ, AQm, AQQI and CQ (within the range 0.1-10.0 mumols l-1). There were no significant differences between the ability of the four compounds to inhibit colony formation but toxicity towards GM-CFU was observed at drug concentrations at least 10-fold lower than those that were toxic to MNL. These data show that the four compounds are equally toxic in vitro toward GM-CFU, although some differences in their toxicity toward MNL were seen. The possible mechanisms of AQ's toxicity are discussed. PMID- 2328197 TI - Comparative effects of ciprofloxacin and lomefloxacin on the oxidative metabolism of theophylline. AB - Nine healthy male volunteers were studied to assess the interaction between theophylline and ciprofloxacin and to assess whether a similar interaction occurred with lomefloxacin, using a randomised, crossover design. Subjects received theophylline 125 mg 8 hourly with and without lomefloxacin 400 mg 12 hourly or ciprofloxacin 500 mg 12 hourly for 7 days. Ciprofloxacin treatment lowered total theophylline clearance by 27%, owing to a decreased clearance via 1 , 3-demethylation and 8-hydroxylation. Lomefloxacin treatment did not alter theophylline clearance. Ciprofloxacin, at usual clinical doses, could cause a clinically significant interaction when co-administered with theophylline. PMID- 2328198 TI - Failure of a nomogram to achieve target aminoglycoside concentrations. PMID- 2328199 TI - The roles of lymph node stromal cells in proliferation of lymphoid leukaemia cells. PMID- 2328200 TI - Clonal analysis of a bladder cancer cell line: an experimental model of tumour heterogeneity. AB - The continuous cell line UCRU BL 17CL was derived from a human invasive bladder cancer and expresses elements of transitional, squamous and glandular differentiation. Nine clones of this line were established by limit dilution and have been extensively characterised. Only six of these clones grew subcutaneously in nude mice. Of these, three have exhibited local invasion, each in one of five implanted mice. Although all xenografts expressed transitional, squamous and glandular elements, different histological subtypes predominated within each clone. Only clones which grew in nude mice formed colonies in semi-solid medium, and each responded differently to the influence of medium that had been conditioned by the growth of UCRU BL 17CL, suggesting the possible secretion of a growth factor by these cells. The DNA content and lectin binding profiles of the clones also reflected the heterogeneity of the line. UCRU BL 17CL and the nine clones provide a unique model for the study of tumour heterogeneity, progression and differentiation, and the potential autocrine regulation of growth of bladder cancer. PMID- 2328201 TI - Synergism between 5-fluorouracil and N-methylformamide in HT29 human colon cancer line. AB - In HT29 cells 5-fluorouracil (5FU) cytotoxicity is enhanced by subsequent incubation of cells in medium containing 1% N-methylformamide (NMF). This enhancement does not appear to be related to differences in the repair of 5FU induced DNA damage. It is proposed that the inhibition of DNA synthesis by NMF (that is reversible and does not result in any detectable toxicity) becomes a lethal event in a cell in which DNA synthesis has already been altered by 5FU exposure. The synergism is sequence dependent (i.e. it does not occur when NMF is given before 5FU) and specific for some cell types as shown by the fact that no synergism was found in L1210 mouse leukaemia cells. In nude mice transplanted s.c. with HT29 cells daily 5FU treatment (for 5 days) followed by daily NMF treatment (for 10 days) caused much greater inhibition of tumour growth than either drug alone or the same combination given in the opposite order (NMF then 5FU). These results, if confirmed on other human colon tumours, could be of clinical interest as a means of increasing the therapeutic efficacy of 5FU in patients with colon cancer. PMID- 2328202 TI - Crypt restricted heterogeneity of goblet cell mucus glycoprotein in histologically normal human colonic mucosa: a potential marker of somatic mutation. PMID- 2328203 TI - Origin of marrow stromal cells and haemopoietic chimaerism following bone marrow transplantation determined by in situ hybridisation. AB - The origin and cell lineage of stromal cells in the bone marrow is uncertain. Whether a common stem cell exists for both haemopoietic and stromal cells or whether these cell lines arise from distinct stem cells is unknown. Using in situ hybridisation for detection of the Y chromosome, we have examined histological sections of bone marrow from seven patients who received marrow transplants from HLA-matched donors of the opposite sex. Stromal cells (adipocytes, fibroblasts, endothelial cells, osteoblasts and osteocytes) were identified in these recipients as being of host origin. This result is consistent with the concept of a distinct origin and separate cell lineage for cells of the haemopoietic and stromal systems. It also shows that engraftment of marrow stromal cell precursors does not occur and that host stromal cells survive conditioning regimens for marrow transplantation. With the exception of one case, with a markedly hypocellular marrow, mixed chimaerism was seen in haemopoietic cells, indicating that this is not a rare event after marrow transplantation. PMID- 2328204 TI - Detection of the growth fraction in colorectal tumours by a monoclonal antibody against DNA polymerase alpha. AB - The cell kinetics of 54 colorectal tumours were examined by immunohistochemical methods, using the monoclonal antibody DNA polymerase alpha which reacts with an antigen found only in proliferating cells. The rate of DNA polymerase alpha positive cells in colorectal cancer was 44.8%, a figure that was significantly higher than the 21.9% found in colorectal adenomas. The rate of DNA polymerase alpha positive cells tended to rise as the degree of differentiation decreased according to the standard histological grading criteria for colorectal cancer. Positive cells were detected in much greater numbers in tumours with liver metastasis (55.4%) than in those without metastasis (41.7%). The rate of DNA polymerase alpha positive cells for aneuploid lesions was higher than that for lesions with a diploid pattern. The determination of growth fractions with a monoclonal antibody (DNA polymerase alpha) may be a biological marker of great prognostic significance. PMID- 2328206 TI - Affinity of IL-2 receptors and proliferation of mitogen activated lymphocytes in Hodgkin's disease. PMID- 2328205 TI - Growth inhibition of Friend erythroleukaemia cell tumours in vivo by a synthetic analogue of prostaglandin A: an action independent of natural killer-activity. AB - Prostaglandins of the A series (PGAs) have been previously shown to inhibit the growth and to stimulate the differentiation of Friend erythroleukaemic cells (FLC) in vitro. In the present report we analysed the effect of PGA treatment in vitro on FLC tumorigenicity, and in vivo on FLC proliferation and on natural killer (NK) activity. PGA1 pretreatment of FLC in vitro for 5 days before inoculation into syngeneic mice slightly delayed tumour appearance, but did not significantly alter the pattern of tumour growth or mice survival, indicating that PGA1, at least in the conditions studied, did not affect FLC tumorigenicity. Daily treatment of mice with a long-acting synthetic analogue of PGA2 (16, 16 dimethyl-PGA2-methyl ester, di-M-PGA2) delayed tumour appearance, inhibited tumour growth, as measured by tumour weight and diameter, and increased the median mice survival time by 15-35%, depending on the schedule of treatment. Daily treatment with di-M-PGA2 strongly suppressed NK activity in normal mice but had no significant effect in tumour-bearing immunodepressed mice. PGA treatment of effector or target cells in vitro, or PGA added during the NK assay, had no effect on NK activity. We suggest that the chemotherapeutic effect of PGA is due to a direct action on tumour cell replication rather than to a stimulation of the host NK activity. PMID- 2328207 TI - Liposome- or LDL-administered Zn (II)-phthalocyanine as a photodynamic agent for tumours. I. Pharmacokinetic properties and phototherapeutic efficiency. AB - The pharmacokinetics of Zn-phthalocyanine (Zn-Pc) in mice bearing a transplanted MS-2 fibrosarcoma has been studied using dipalmitoyl-phosphatidylcholine (DPPC) liposomes and low density lipoproteins (LDL) as drug delivery systems. LDL induce a higher Zn-Pc uptake by the tumour and improve the selectivity of tumour targeting as compared to DPPC liposomes. Experimental photodynamic therapy (PDT) of the MS-2 fibrosarcoma has been performed using liposome-delivered Zn-Pc and the efficiency of tumour necrosis has been measured following four different irradiation protocols. We found that Zn-Pc doses as low as 0.07-0.35 mg kg-1 are sufficient for inducing an efficient tumour response that is linearly dependent on the injected dose. The amount of Zn-Pc in the tumour decreases very slowly as a function of time, hence PDT gives satisfactory results even if performed at relatively long time intervals after administration. PMID- 2328208 TI - Effect of 5-fluorouracil combination therapy on RNA processing in human colonic carcinoma cells. AB - We have evaluated the RNA-directed cytotoxicity of 5-fluorouracil (5-FU) in human colonic carcinoma cells. The mode of action of 5-FU and its effects on human pre rRNA processing were then examined. From these data, possible reasons why the disruption of pre-rRNA maturation could induce cytotoxic effects are considered. The results imply that inhibition of thymidylate synthase is not the sole primary cytotoxic lesion in this cell line. First, exogenous thymidine (dTHd) enchanced cytotoxicity. Second, addition of dThd to the cells was found to enhance incorporation of 5-FU into total cellular RNA. Third, 5-FU disrupted rRNA processing by a different mechanism from actinomycin D and methotrexate (MTX), suggesting that the inhibition was not just a consequence of cell death. Finally, the addition of dThd was found to enhance the disruption of rRNA processing consistent with an increase in concentration of 5-FU. These data are discussed in the light of literature reports and their potential for optimising 5-FU protocols. PMID- 2328209 TI - The potential of carboxypeptidase G2: antibody conjugates as anti-tumour agents. II. In vivo localising and clearance properties in a choriocarcinoma model. AB - The in vivo localising and clearance properties of conjugates of the folate degrading enzyme carboxypeptidase G2 (CPG2) with anti-human chorionic gonadotrophin (W14A) were measured in nude mice bearing CC3 choriocarcinoma xenografts. Conjugates of W14A-F (ab')2 fragment coupled to CPG2 localised in tumour as effectively as native antibody alone but showed lower uptake in other major tissues. The clearance rates of conjugates prepared with intact antibody or F (ab')2 fragment were shown to be up to five-fold faster than for native antibody and two-fold compared to F (ab')2 fragment. Molecular weight analysis of residual conjugate in the blood showed that no degradation of conjugate to its component molecules occurred during circulation. It was concluded that F (ab')2: CPG2 conjugates offered the greatest potential for targeting applications. PMID- 2328210 TI - Cytogenetic study in therapy-related myelodysplastic syndromes (t-MDS) and acute non-lymphocytic leukaemia (t-ANLL). AB - A cytogenetic study was performed in 27 patients suspected of t-MDS or t-ANLL. In 12 patients the diagnosis of t-MDS or t-ANLL was confirmed by morphological, cytochemical and immunophenotypical analysis. The cases were classified as RA (one), RAEB (four), CMML (two), ANLL (five). They had received chemotherapy and/or RT for Hodgkin's disease (eight cases), solid tumours (three cases) and multiple myeloma (one case). Clonal chromosome abnormalities were found in bone marrow or peripheral blood cells in all the 12 cases. Five patients had a clonal abnormality of chromosome no. 5 (monosomy, deletions, translocation and inversion of 5q). The critical region on chromosome no. 5 comprised bands q12-q34. Monosomy and deletion of chromosome 7q was observed in the other two patients. In the six remaining patients various karyotypic patterns were observed including a t(4;11) (q21;q23) in one case, monosomies (four cases) and trisomies (one case) of different chromosomes. In the other 15 cases, the presence of a normal karyotype together with the morphological and immunophenotypical characterisation was consistent with a diagnosis of non-neoplastic specimens. PMID- 2328211 TI - Evidence that multiple myeloma may be regulated by homeostatic control mechanisms: correlation of changes in the number of clonogenic myeloma cells in vitro with clinical response. AB - Myeloma colonies (MY-CFUc) could be grown in vitro for 6 months (median time) after a group of 12 myeloma patients had reached complete remission (CR). In a second group of 25 patients MY-CFUc increased in 17/25 and GM-CFUc in 20/25 patients after cyclophosphamide even though 24/25 patients had a partial response to VAMP and one was in CR. These data suggest that cell killing by cyclophosphamide stimulates residual tumour cells into proliferation and adds further support to the idea that myeloma is under some degree of homeostatic control which may be analogous to that in normal bone marrow. Although lymphoplasmacytoid myeloma cells may be more drug resistant than plasmacytoid myeloma cells in vitro, it was not possible to conclude that the emergence of lymphoplasmacytoid cells at relapse was indicative of resistance to further treatment. PMID- 2328212 TI - A prognostic score in histological node negative breast cancer. AB - Between October 1977 and December 1983, 379 consecutive patients have been treated for unilateral, non-metastatic breast cancer, either with conservative (n = 205) or radical surgery (n = 174), with axillary dissection in all the cases. None of them had histologically proved lymph node involvement. Oestrogen receptor (ER) and progesterone receptor (PR) levels were measured on each tumour. Levels greater than 5 fmol mg-1 cytosolic protein were considered as positive for both ER and PR. At 5 years, overall survival (OS) and disease-free survival (DFS) are respectively 88% and 78%. Unifactorial analysis using Kaplan and Meier estimates and the log rank test revealed that OS was significantly related to age (P less than 0.05), tumour size (P less than 0.001), histological grading (SBR) (P less than 0.01), ER (P less than 0.001) and PR (P less than 0.001). DFS was significantly related to the same factors. Menopausal status, number of breast tumour foci and previous familial history of breast cancer were not significant. Multifactorial analysis revealed that DFS was significantly related to age (bad prognosis (b.p.) less than or equal to 37 years old), tumour size and histological grading (b.p. SBR = 3), and that OS was significantly related to tumour size and PR (b.p. PR less than or equal to 5 fmol mg-1 protein). A prognostic score has been constructed for both DFS and OS. These scores divide our patients into three significantly different (P less than 0.0001) groups with good, intermediate and bad prognosis. PMID- 2328213 TI - How frequent is spontaneous remission of neuroblastomas? Implications for screening. AB - The 'true' incidence of spontaneous regression of neuroblastomas is uncertain. However, the frequency of spontaneous regression is important when the benefits of screening procedures are considered. In the population-based Danish neuroblastoma survey 1943-80, spontaneous regression was documented in less than 2% of cases. However, the 'true' incidence may be higher. The epidemiological findings of increased incidence and survival rates with an unchanged mortality rate may suggest the inclusion of borderline lesions among 'truly' malignant neuroblastomas in recent decades in Denmark. However, it is more likely to be a result of improved diagnosis, changes in the social composition of the population and possibly unidentified environmental agents. However, if some premalignant lesions in fact had been included, they are most likely to be stages I-II tumours of infancy. In this study we describe cases of spontaneous regression of neuroblastoma from the Danish population-based survey 1943-80. PMID- 2328215 TI - Milk consumption and cancer incidence: a Norwegian prospective study. AB - Relationships between milk intake and cancer incidence were investigated after 11 1/2 years of follow-up of 15,914 individuals. A diagnosis of cancer was made in a total of 1,422 individuals. No association was established with total cancer incidence, in analyses adjusted for sex, age and residential characteristics. However, a strong positive association with milk consumption was observed for cancers of the lymphatic organs (odds ratio 3.4 for greater than or equal to 2 glasses per day vs less than 1; 95% confidence interval 1.4-8.2). An inverse association was found for cancer of the bladder. Kidney cancer and cancers of the female reproductive organs (except the uterine cervix) showed weak positive associations with milk intake. PMID- 2328214 TI - Phase I/II study of the anti-oestrogen zindoxifene (D16726) in the treatment of advanced breast cancer. A Cancer Research Campaign Phase I/II Clinical Trials Committee study. AB - We report a phase I/II study of the indole derivative, zindoxifene, an anti oestrogen with intrinsic oestrogenic activity. We have treated 28 women with advanced breast cancer of whom 26 had received prior endocrine therapy. Oral zindoxifene doses ranged from 10 to 100 mg daily; doses were escalated in some patients. Twenty-five patients were assessed for response; the remaining three patients completed less than 3 weeks of treatment. There were no objective responses; disease stabilised in seven patients for up to 5 months and progressed in the remaining 18. Five patients (including three treated with tamoxifen) responded to subsequent endocrine therapy. Nausea, which was dose-limiting, affected half of the patients treated with 80 mg daily. Metabolites of zindoxifene were detectable in serum at all doses used, and sex hormone binding globulin (SHBG) levels showed a strong tendency to rise at the higher doses, indicating that zindoxifene is absorbed and has biological activity. We conclude that zindoxifene in the doses used in this study has only marginal therapeutic activity in the treatment of advanced breast cancer. PMID- 2328216 TI - Measures of mortality in prostatic cancer. AB - The use of different expressions of mortality in prostate cancer can lead to difficulty in comparing reported data. We have used different measures of mortality in the same group of 438 patients presenting consecutively with histologically proven adenocarcinoma of the prostate, in order to assess the values and deficiencies of each method. The use of expected and relative survival is shown to be valuable in allowing indirect but objective assessment of disease specific mortality in prostatic cancer. PMID- 2328217 TI - Recombinant interleukin-2 (rIL-2) with flavone acetic acid (FAA) in advanced malignant melanoma: immunological studies. AB - Natural killer (NK) cell activity and lymphokine activated killer (LAK) cell cytotoxicity were measured in patients receiving recombinant interleukin 2 (rIL 2) and flavone acetic acid (FAA) for treatment of progressing metastatic melanoma. NK activity was increased in 23 of 26 patients and LAK activity induced in 13 of 26 patients. However, levels of cytotoxicity in the present study were not significantly greater than a previous study using rIL-2 alone. LAK cell precursors demonstrated by in vitro incubation of pretreatment lymphocytes with IL-2 and subsequent cytotoxicity were no different in the patients compared to normal controls. Analysis of cell surface phenotypes failed to reveal any significant changes in the cell populations examined, including IL-2R and Leu 19. Although five patients had tumour response, one being complete, there was no correlation with the immunological parameters examined. PMID- 2328218 TI - The assessment of treatment response in non-Hodgkin's lymphoma by image guided 31P magnetic resonance spectroscopy. AB - Serial image guided 31P magnetic resonance spectroscopy (MRS) studies were performed in eight patients with non-Hodgkin's lymphoma to determine the changes in phosphorus metabolites that occur in vivo in response to chemotherapy. Pre treatment spectral characteristics were different in high and low grade lymphoma. A larger inorganic phosphate (Pi) peak was seen in high grade NHL relative to phosphomonoesters (PME) or beta adenosine triphosphate (beta ATP), producing significant differences in the PME/Pi and Pi/beta ATP metabolite ratios, and probably reflecting a larger hypoxic cell fraction within the high grade lymphomas. Consistent metabolite changes were seen with treatment, and before reductions in tumour bulk had occurred. Alterations in tumour energetics with changes in Pi and beta ATP, and increases in phospholipid turnover reflected as an increase in the phosphodiester (PDE) resonance were detected. Changes were seen between days 10 and 27 in low grade lymphoma treated with oral alkylating therapy and between days 1 and 5 in lymphoma treated with intensive combination chemotherapy. Increases in the PDE/beta ATP metabolite ratio may be an early indicator of response to chemotherapy in human tumours. These studies illustrate the feasibility and clinical potential of image guided 31P MRS as a means of assessing response to therapy. PMID- 2328219 TI - Hyperbilirubinaemia in patients treated with recombinant human interleukin-2 (rIL 2) PMID- 2328220 TI - Role of manmade mineral fibres in the causation of cancer. PMID- 2328221 TI - Chronic pleuritic pain in four patients with asbestos induced pleural fibrosis. AB - Four patients occupationally exposed to asbestos, each suffering at least eight years of disabling, persistent, and often bilateral pleuritic pain are described. Radiographic evidence of pleural disease ranged from plaques seen only on computed tomography to typical bilateral plaques or diffuse thickening to extensive diffuse and circumscribed pleural fibrosis and calcification. There was no history or evidence of acute pleuritis or pleural effusion in three patients. Intermittent pleural friction rubs have been present in all four; one patient showed pleural uptake of gallium-67. Extensive workups including repeated pulmonary ventilation-perfusion scans and cardiac catheterisation have not yielded other diagnoses to explain the pain. It is proposed that persistent pleuritic pain be added to the manifestations of benign asbestos induced pleural disease. PMID- 2328222 TI - Evidence that a beta-N-glucuronide of 4,4'-methylenebis (2-chloroaniline) (MbOCA) is a major urinary metabolite in man: implications for biological monitoring. AB - Urine samples from workers exposed to 4,4'-methylenebis (2-chloroaniline) (MbOCA) contain a labile metabolite(s) that, on hydrolysis, yields the parent compound at concentrations two to three times those of free MbOCA. Evidence has now been obtained that the major labile metabolite is an N-glucuronide of MbOCA. The N glucuronide of MbOCA was synthesised chemically, characterised by thermospray mass spectrometry, and found to have a pseudomolecular (M + 1) ion at m/z 443/445. MbOCA and [14C] uridine diphosphoglucuronic acid [( 14C]UDPGA) were incubated with liver microsomes from rats induced with polychlorinated biphenyls. The stoichiometry of the reaction product was about 1:1 (MbOCA:UDPGA). This product, the chemically synthesised glucuronide, and the labile urinary metabolite had identical chromatographic and hydrolytic (heat and beta glucuronidase) properties. These studies show that the major labile conjugate of MbOCA in the urine of workers exposed to this compound is probably the mono N glucuronide. In view of the lability of this compound and the fact that its concentration in urine is two to three times that of free MbOCA, it is essential that any strategy for the biological monitoring of exposed workers takes into account the N-glucuronide. PMID- 2328223 TI - Cancer and other causes of death among a cohort of dry cleaners. AB - Mortality among 5365 members of a dry cleaning union in St. Louis, Missouri, was less than expected for all causes combined (SMR = 0.9) but slightly raised for cancer (SMR = 1.2). Among the cancers, statistically significant excesses occurred for oesophagus (SMR = 2.1) and cervix (SMR = 1.7) and non-significant excesses for larynx (SMR = 1.6), lung (SMR = 1.3), bladder (SMR = 1.7), thyroid (SMR = 3.3), lymphosarcoma and reticulosarcoma (SMR = 1.7), and Hodgkin's disease (SMR = 2.1). Mortality from emphysema was also significantly raised (SMR = 2.0). Eleven of the 13 deaths from oesophageal cancer occurred among black men. The risk of this cancer showed a significant association with estimated cumulative exposure to dry cleaning solvents (rising to 2.8-fold in the highest category) but not with level or duration of exposure. Mortality from kidney cancer was not excessive as reported in other studies. Excesses for emphysema and cancers of the larynx, lung, oesophagus, bladder, and cervix may be related to socioeconomic status, tobacco, or alcohol use. Although the number of deaths was small, the greatest risk for cancers of the lymphatic and haematopoietic system (fourfold) occurred among workers likely to have held jobs where exposures were the heaviest. Small numbers and limited information on exposure to specific substances complicates interpretation of this association but is unlikely to be due to confounding by tobacco use. It was not possible to identify workers exposed to specific dry cleaning solvents but mortality among those entering the union after 1960, when use of perchloroethylene was predominant, was similar to those entering before 1960. PMID- 2328225 TI - Mortality experience of haematite mine workers in China. AB - The mortality risk of iron ore (haematite) miners between 1970 and 1982 was investigated in a retrospective cohort study of workers from two mines, Longyan and Taochong, in China. The cohort was limited to men and consisted of 5406 underground miners and 1038 unexposed surface workers. Among the 490 underground miners who died, 205 (42%) died of silicosis and silicotuberculosis and 98 (20%) of cancer, including 29 cases (5.9%) of lung cancer. The study found an excess risk of non-malignant respiratory disease and of lung cancer among haematite miners. The standardised mortality ratio for lung cancer compared with nationwide male population rates was significantly raised (SMR = 3.7), especially for those miners who were first employed underground before mechanical ventilation and wet drilling were introduced (SMR = 4.8); with jobs involving heavy exposure to dust, radon, and radon daughters (SMR = 4.2); with a history of silicosis (SMR = 5.3); and with silicotuberculosis (SMR = 6.6). No excess risk of lung cancer was observed in unexposed workers (SMR = 1.2). Among current smokers, the risk of lung cancer increased with the level of exposure to dust. The mortality from all cancer, stomach, liver, and oesophageal cancer was not raised among underground miners. An excess risk of lung cancer among underground mine workers which could not be attributed solely to tobacco use was associated with working conditions underground, especially with exposure to dust and radon gas and with the presence of non-malignant respiratory disease. Because of an overlap of exposures to dust and radon daughters, the independent effects of these factors could not be evaluated. PMID- 2328224 TI - Mortality and incidence of cancer among Swedish gas workers. AB - The mortality and incidence of cancer was studied among 295 workers at a Swedish gas production company. All men employed for at least one year between 1965 and 1972 were included in the study. The follow up period for mortality was 1966 to 1986, and the incidence of cancer was followed up from 1966 to 1983. Expected numbers of deaths were based on local death rates among occupationally active men, the expected numbers of cancer were based on national statistics. The total mortality was increased, mainly due to an excess of deaths from circulatory diseases. The excess was larger after long follow up and after long employment periods. Two cases of cancer in the nose and nasal sinuses were found; there was no excess of lung cancer. Smoking habits were investigated for a subset of the cohort and did not differ from the average for men in large cities. The findings are discussed in relation to other studies of soot and combustion exposed workers. PMID- 2328227 TI - Cardiac arrhythmia in refrigerator repairmen exposed to fluorocarbons. AB - A field study of 89 refrigerator repairmen was carried out to ascertain whether occupational exposure to fluorocarbons induces cardiac arrhythmia. The concentrations of fluorocarbons in the breathing zones and the heart activity were recorded simultaneously. Most cooling systems contained FC 12 or FC 22. The highest level recorded in one minute was 14,000 ppm and the highest time weighted level during eight hours was 280 ppm. Two types of arrhythmia were recorded, ectopic beats and sudden bradycardia. A within subject comparison design was applied and the main parameter was the difference in arrhythmia frequencies between exposed and unexposed periods. No appreciable differences between exposed and unexposed periods and no consistent dose effect relations were observed, although subjects in the medium exposure category showed a difference of borderline significance (Wilcoxon's test: p = 0.05, one tailed). The frequencies of arrhythmia when unexposed were somewhat higher than previously reported. Misclassification of the exposure and the possible confounding effect of physical workload and psychological strain may have obscured a causal relation and therefore a minor effect cannot be ruled out. The results do not support the notion that fluorocarbons induce cardiac arrhythmia in occupationally exposed refrigerator repairmen. PMID- 2328226 TI - Environmental and biological monitoring of exposure to ethylenebisdithiocarbamate fungicides and ethylenethiourea. AB - Exposure of workers to ethylenebisdithiocarbamates (EBDCs; maneb or mancozeb) in 29 potato farms was evaluated during the control of potato late blight. Concentrations of EBDCs and ethylenethiourea (ETU), an impurity and degradation product in EBDC formulations, in ambient air were evaluated during pesticide application. Biological monitoring of exposure to EBDCs was carried out by measuring the concentrations of ETU, a metabolite of EBDCs, in urine for 22 days after the end of the exposure. The estimated inhaled doses of ETU and EBDCs during the average four hour application period were 0.07 and 1.8 micrograms/kg, respectively. Only 1-10% of ETU on the clothes reached the skin. The creatinine corrected concentrations of ETU in urine were 0.1-2.5 micrograms/mmol creatinine 24 hours after exposure ended. The estimated half life for eliminating ETU through the kidneys was close to 100 hours. These results indicate that the measurement of ETU in urine is suitable for biological monitoring of exposure to EBDCs. PMID- 2328228 TI - Occupational risk factors for nasopharyngeal cancer in Sweden. PMID- 2328229 TI - 500-picosecond molecular dynamics in water of the Man alpha 1----2Man alpha glycosidic linkage present in Asn-linked oligomannose-type structures on glycoproteins. AB - Molecular dynamics simulations of the Man alpha 1----2Man alpha glycosidic linkage found in the N-linked glycans of glycoproteins were performed in vacuo and in the presence of water. In the latter case significant dampening of the molecular fluctuations was found when compared to the in vacuo simulation. A 500 ps dynamics simulation in water showed only occasional short-lived deviations from the minimum-energy conformation, more consistent with carbohydrate "breathing" than flexibility. These studies add further evidence that oligosaccharides can maintain "fixed" geometries with relatively long lifetimes and are in agreement with experimental NMR-derived parameters for the same linkage in oligomannose structures. PMID- 2328230 TI - Pyrimidine 5-methyl groups influence the magnitude of DNA curvature. AB - DNA containing short sequences of the form (dA)n.(dT)n can exhibit pronounced degrees of stable curvature of the helix axis, provided that these homooligomeric stretches are approximately in phase with the helix repeat. However, the precise origin of this effect is unknown. We have observed that pyrimidine 5-methyl groups can have a significant effect on the degree of curvature, depending on their locations within the homooligomeric sequences. Such effects are observed in both (dA)n.(dT/dU)n and (dI)n.(dC/d5meC)n sequence motifs, arguing for a general structural perturbation due to the methyl group. The current observations suggest that pyrimidine methyl groups could influence protein-DNA interactions not only through direct protein-methyl group contacts but also by methyl group induced alterations in local DNA structure. PMID- 2328231 TI - Structural properties of apocytochrome b5: presence of a stable native core. AB - Upon removal of the heme group, the water-soluble fragment of cytochrome b5 adopts a conformation less stable and compact than that of the holoprotein [Huntley, T. E., & Strittmatter, P. (1972) J. Biol. Chem. 247, 4641-4647]. This conformation, imposed by the amino acid sequence alone, has not been described in detail. One- and two-dimensional proton nuclear magnetic resonance spectroscopy techniques were applied to the apoprotein of the soluble fragment of rat liver cytochrome b5 in an effort to characterize the structure of the apoprotein. Nuclear Overhauser spectroscopy revealed a number of short interresidue distances and demonstrated that, in spite of the increased flexibility, at least one cluster of side chains exists on a time scale long enough for study. Several residues participating in the cluster, in particular the only Trp (Trp 22), were identified. Similarities with the spectrum of the reduced holoprotein were observed that led to the inspection of the cytochrome b5 crystal structure for assigning resonances. It appeared that the environment of this residue maintains its integrity in the apoprotein. Since in the holoprotein Trp 22 belongs to a hydrophobic core formed in part by beta-strands, it is proposed that some of this beta-structure is stable in the absence of the heme-protein interactions. Implications for structure and folding are discussed. PMID- 2328232 TI - Kinetics of fusion and lipid transfer between virus receptor containing liposomes and influenza viruses as measured with the octadecylrhodamine B chloride assay. AB - Octadecylrhodamine B chloride (R18) and ganglioside GD1a (virus receptor) were incorporated into small unilamellar liposomes [Hoekstra et al. (1984) Biochemistry 23, 5675-5681]. Upon interaction of these liposomes with PR8 influenza viruses without prebinding, two types of dequenching were observed at 37 degrees C, both second-order processes: a fast reaction at pH 5.3, 2k = 17.53 x 10(-3) (Q.s)-1, and a slow reaction at pH 7.4, 2k = 0.335 x 10(-3) (Q.s)-1. The maximal level of dequenching was the same for both. Upon prebinding of liposomes to PR8 viruses (30 min, 0 degrees C, pH 7.4) at high concentrations, a very fast dequenching occurred when the prebinding mixture was diluted into prewarmed (37 degrees C) 10 mM PBS, pH 5.3. For the initial phase, a first-order rate constant of 0.5 s-1 could be extrapolated. After a quick drop in velocity during the first 30 s, the reaction was kinetically indistinguishable from the one found without prebinding. A second-order process with 2k = 16.52 x 10(-3) (Q.s)-1 became rate limiting. The fast reactions at pH 5.3 can be abolished by inactivation or removal of the virus hemagglutinin. We conclude that the reaction at pH 5.3 reflects the hemagglutinin-dependent fusion process known to occur between influenza viruses and partner membranes at low pH; however, second-order kinetics indicate that specific binding rather than fusion is the rate-limiting step. For the slow dequenching, which is not affected by prebinding, the rate constant is 20 times lower than for the fast reaction, and the process is independent of viral hemagglutinin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328233 TI - Effect of partial delipidation of purple membrane on the photodynamics of bacteriorhodopsin. AB - The effect of lipid-protein interaction on the photodynamics of bacteriorhodopsin (bR) was investigated by using partially delipidated purple membrane (pm). When pm was incubated with a mild detergent, Tween 20, the two major lipid components of pm, phospholipids and glycolipids, were released in different ways: the amount of phospholipids released was proportional to the logarithm of the incubation time; the release of glycolipids became noticeable after the release of approximately 2 phospholipids/bR, but soon leveled off at approximately 50% of the initial content. It was found that the thermal decay of the photocycle intermediate N560 was inhibited by the removal of less than 2 phospholipids per bR. This inhibition was partly explained by an increase in the local pH near the membrane surface. More significant changes in the bR photoreactions were observed when greater than 2 phospholipids/bR were removed: (1) the extent of light adaptation became much smaller, and this reduction correlated with the release of glycolipids; (2) N560 became difficult to detect; (3) the M412 intermediate, which is characterized by a pH-insensitive lifetime, was replaced by a long-lived M-like photoproduct with a pH-sensitive lifetime. The heavy delipidation apparently altered the mechanism by which the deprotonated Schiff base receives a proton. An important conformational change in the protein moiety is suggested to take place during the M412 state, this conformational change being inhibited in the rigid lipid environment. PMID- 2328234 TI - A high-pressure, infrared spectroscopic study of the solvation of bilirubin in lipid bilayers. AB - The location of bilirubin IXa in lipid bilayers of dimyristoylphosphatidylcholine or dioleoylphosphatidylcholine was studied by determining the effects of bilirubin on the infrared spectra of the lipids as a function of pressure. It was found for both bilayers that bilirubin intercalated into the polymethylene chain region of the bilayer, being located between the carbonyl region and the methylene group two carbons from the methyl terminus. Small amounts of bilirubin interacted with the choline region of dioleoylphosphatidylcholine. Lesser amounts interacted with the choline region of dimyristoylphosphatidylcholine. This difference between the two types of bilayers was attributed to the degradation of small amounts of bilirubin IXa to more polar isomers in the presence of dioleoylphosphatidylcholine. In dioleoyl- but not dimyristoylphosphatidylcholine, bilirubin interacted with the C = O region, probably indicating that bilirubin in the latter type of bilayer was intercalated into the polymethylene chains above and below the double bond. Bilirubin decreased the pressure required for the liquid-crystal to gel-phase transition in both bilayers at 28 degrees C. Bilirubin was not forced out of either bilayer at pressures as high as 20 kbar. PMID- 2328235 TI - High-pressure infrared study of phosphatidylserine bilayers and their interactions with the local anesthetic tetracaine. AB - High-pressure Fourier-transform infrared (FT-IR) spectroscopy was used to study the barotropic behavior of phosphatidylserine bilayers and their interactions with the local anesthetic tetracaine. The model membrane systems studied were multilamellar aqueous dispersions of 1,2-dimyristoyl-sn-glycero-3-phospho-L serine (DMPS) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) in the absence and the presence of tetracaine at pH 5.5 and 9.5. The infrared spectra were measured at 28 degrees C in a diamond anvil cell as a function of pressure up to 25 kbar. The results show that the barotropic behavior of the negatively charged phosphatidylserine bilayers is very similar to that observed for zwitterionic phospholipids, such as phosphatidylcholine and phosphatidylethanolamine, with corresponding acyl chains. The results also indicate that the local anesthetic partitions into phosphatidylserine bilayers in an environment close to the membrane-water interface and interacts electrostatically with the lipid head group. Application of high hydrostatic pressure on the lipid-anesthetic systems results in the pressure-induced expulsion of the anesthetic from a membrane to an aqueous environment. The pressures required for expulsion of anesthetic from bilayers are much higher for the unsaturated lipid (DOPS) than for the saturated lipid (DMPS) (approximately 6 kbar vs approximately 2 kbar, respectively). Whereas incorporation of the anesthetic into DOPS bilayers does not affect significantly the structural and dynamic properties of the disordered acyl chains in the liquid-crystalline phase, it orders the DMPS acyl chains in the gel phase. PMID- 2328236 TI - Protein-mediated phospholipid translocation in the endoplasmic reticulum with a low lipid specificity. AB - The outside-inside translocation rate of various amphiphilic spin-labeled phospholipids has been measured in rat liver endoplasmic reticulum vesicles. The eight spin-labels tested experienced a fast flip-flop rate with the same half time of approximately 20 min at 37 degrees C. The stationary distribution of these phospholipid analogues was ca. 45% on the inner vesicular leaflet and 55% on the external one, showing that there is no net enrichment of some lipid in one layer under the experimental conditions used. The initial rate of translocation was reduced 4-fold if membranes were preincubated with N-ethylmaleimide (2 mM) and was about an order of magnitude lower in liposomes made from the extracted lipids. An apparent saturability of the transbilayer diffusion can be deduced from the variation of the initial velocity of the relocation kinetics vs the amount of analogue incorporated in the membrane. Moreover, translocation rates of two different spin-labeled phospholipids introduced simultaneously in the membrane were almost equally reduced by the presence of the other lipid. On the other hand, no competition between the water-soluble dibutyroylphosphatidylcholine and the amphiphilic spin-labeled phospholipids could be detected. Overall, these results suggest that phospholipid translocation in the endoplasmic reticulum is a protein-mediated process with a low specificity, which tends, in the absence of any other metabolic event, to equilibrate the phospholipid composition of the two membrane halves. PMID- 2328237 TI - Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 1. Phase behavior and aggregation states of model lipid systems patterned after aqueous duodenal contents of healthy adult human beings. AB - We developed equilibrium phase diagrams corresponding to aqueous lipid compositions of upper small intestinal contents during lipid digestion and absorption in adult human beings. Ternary lipid systems were composed of a physiological mixture of bile salts (BS), mixed intestinal lipids (MIL), principally partially ionized fatty (oleic) acid (FA) plus racemic monooleylglycerol (MG), and cholesterol (Ch), all at fixed aqueous-electrolyte concentrations, pH, temperature, and pressure. The condensed phase diagram for typical physiological conditions (1 g/dL total lipids, FA:MG molar ratio of 5:1, pH 6.5, 0.15 M Na+ at 37 degrees C) was similar to that of a dilute model bile [BS/lecithin (PL)/Ch] system [Carey, M. C., & Small, D. M. (1978) J. Clin. Invest. 61, 998-1026]. We identified two one-phase zones composed of mixed micelles and lamellar liquid crystals, respectively, and two two-phase zones, one composed of Ch monohydrate crystals and Ch-saturated micelles and the other of physiologic relevance composed of Ch- and MIL-saturated mixed micelles and unilamellar vesicles. A single large three-phase zone in the system was composed of Ch-saturated micelles, Ch monohydrate crystals, and liquid crystals. Micellar phase boundaries for otherwise typical physiological conditions were expanded by increases in total lipid concentration (0.25-5 g/dL), pH (5.5-7.5), and FA:MG molar ratio (5-20:1), resulting in a reduction of the size of the physiological two-phase zone. Mean particle hydrodynamic radii (Rh), measured by quasielastic light scattering (QLS), demonstrated an abrupt increase from micellar (less than 40 A) to micelle plus vesicle sizes (400-700 A) as this two-phase zone was entered. With relative lipid compositions within this zone, unilamellar vesicles formed spontaneously following coprecipitation, and their sizes changed markedly as functions of time, reaching equilibrium values only after 4 days. Further, vesicle Rh values were influenced appreciably by MIL:mixed bile salt (MBS) ratio, pH, total lipid concentration, and FA:MG ratio, but not by Ch content. In comparison, micellar systems equilibrated rapidly, and their Rh values only slightly influenced by physical-chemical variables of physiological importance. In contrast to the BS-PL-Ch system [Mazer, N. A., & Carey, M. C. (1983) Biochemistry 22, 426-442], no divergence in micellar sizes occurred as the micellar phase boundary was approached. The ionization state of FA at simulated "intestinal" pH values (5.5-7.5) in the micellar and physiologic two-phase zones was principally that of 1:1 sodium hydrogen dioleate, an insoluble swelling "acid soap" compound. By phase separation and analysis, tie-lines for the constituent phase in the two-phase zone demonstrated that the mixed micelles were saturated with MIL and Ch and the coexisting vesicles were saturated with MBS, but not with Ch.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2328239 TI - Reactions of the NAD radical with higher oxidation states of horseradish peroxidase. AB - The reactions of the NAD radical (NAD.) with ferric horseradish peroxidase and with compounds I and II were investigated by pulse radiolysis. NAD. reacted with the ferric enzyme and with compound I to form the ferrous enzyme and compound II with second-order rate constants of 8 X 10(8) and 1.5 X 10(8) M-1 s-1, respectively, at pH 7.0. In contrast, no reaction of NAD. with native compound II at pH 10.0 nor with diacetyldeutero-compound II at pH 5.0-8.0 could be detected. Other reducing species generated by pulse radiolysis, such as hydrated electron (eaq-), superoxide anion (O2-), and benzoate anion radical, could not reduce compound II of the enzyme to the ferric state, although the methylviologen radical reduced it. The results are discussed in relation to the mechanism of catalysis of the one-electron oxidation of substrates by peroxidase. PMID- 2328238 TI - Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestion in healthy adult human beings. AB - Following the feeding of a triacylglycerol-rich meal to healthy adult human beings, duodenal contents were aspirated for ex vivo chemical and physical chemical analyses. The aspirates were collected during established lipid digestion and absorption into a "cocktail" of chemical inhibitors that rapidly inhibited ex vivo lipolysis. Following ultracentrifugation, the lipids separated into a floating oil layer, several interfacial layers, a "clear" or turbid "subphase", and a precipitated "pellet". By chemical and phase analyses, the floating layer was composed of oil-in-water emulsion particles with cores of triacylglycerol (TG), diacylglycerols (DG), and cholesteryl esters (CE) emulsified with a surface coat of partially ionized fatty acids (FA), monoacylglycerols (MG), diacylphosphatidylcholine (PL), and bile salts (BS). The interfacial layers contained similar emulsion particles dispersed among excess emulsifier which adopted a lamellar liquid-crystalline structure. Precipitated pellets were composed principally of emulsifying lipids, with smaller amounts of crystalline calcium soaps and BS. Relative lipid compositions of all but three subphases fell within a two-phase region of the condensed ternary phase diagram (Staggers et al., 1990, companion paper) where saturated mixed micelles composed of BS, FA "acid-soaps", MG, PL, cholesterol (Ch), and traces of DG (and TG) coexisted with unilamellar liquid-crystalline vesicles composed of the same lipids. Attempts to achieve clean separation of vesicles from micelles by repeat ultracentrifugation failed. Compared with the structure and sizes of lipid particles in equilibrated model systems (Staggers et al., 1990), quasielastic light scattering (QLS) analysis revealed that ex vivo micellar sizes (mean hydrodynamic radii, Rh) were similar (less than or equal to 40 A), whereas unilamellar vesicle sizes (Rh = 200-600 A) were appreciably smaller. Two component QLS analysis of the subphases showed that much larger proportions of lipids were solubilized by micelles than were dispersed as unilamellar vesicles. When followed as functions of time, vesicles frequently dissolved spontaneously into mixed micelles, indicating that, in the nonequilibrium in vivo conditions, the constituent micellar phase was often unsaturated with lipids. These results are consistent with the hypothesis that, during hydrolysis of emulsified DG and TG by luminal lipases, unilamellar vesicles originate in lamellar liquid crystals that form at emulsion-water interfaces in the upper small intestine. In a BS replete environment, unilamellar vesicles probably represent the primary dispersed product phase of human fat digestion and facilitate the dissolution of lipolytic products into unsaturated mixed micelles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2328240 TI - Characterization of the oxycomplex of lignin peroxidases from Phanerochaete chrysosporium: equilibrium and kinetics studies. AB - The oxycomplexes (compound III, oxyperoxidase) of two lignin peroxidase isozymes, H1 (pI = 4.7) and H8 (pI = 3.5), were characterized in the present study. After generation of the ferroperoxidase by photochemical reduction with deazoflavin in the presence of EDTA, the oxycomplex is formed by mixing ferroperoxidase with O2. The oxycomplex of isozyme H8 is very stable, with an autoxidation rate at 25 degrees C too slow to measure at pH 3.5 or 7.0. In contrast, the oxycomplex of isozyme H1 has a half-life of 52 min at pH 4.5 and 29 min at pH 7.5 at 25 degrees C. The decay of isozyme H1 oxycomplex follows a single exponential. The half lives of lignin peroxidase oxycomplexes are much longer than those observed with other peroxidases. The binding of O2 to ferroperoxidase to form the oxycomplex was studied by stopped-flow methods. At 20 degrees C, the second-order rate constants for O2 binding are 2.3 X 10(5) and 8.9 X 10(5) M-1 s-1 for isozyme H1 and 6.2 X 10(4) and 3.5 X 10(5) M-1 s-1 for isozyme H8 at pH 3.6 and pH 6.8, respectively. The dissociation rate constants for the oxycomplex of isozyme H1 (3.8 Z 10(-3) s-1) and isozyme H8 (1.0 X 10(-3) s-1) were measured at pH 3.6 by CO trapping. Thus, the equilibrium constants (K, calculated from kon/koff) for both isozymes H1 (7.0 X 10(7) M-1) and H8 (6.2 X 10(7) M-1) are higher than that of myoglobin (1.9 Z 10(6) M-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328241 TI - Synthesis and characterization of the dansyltyrosine derivatives of porcine pancreatic colipase. AB - Steady-state and time-resolved fluorescence techniques were used to study dansyltyrosine derivatives of porcine pancreatic colipase. Nitration, reduction, acylation, and dansylation reactions were utilized to synthesize two fluorescently labeled colipases: (o-aminodansyltyrosine 55 porcine colipase) (DNStyr55PC) and o-aminodansyltyrosine 59 porcine colipase (DNStyr59PC). DNStyr55PC was 200% active, while the DNStyr59 derivative maintained 80% activity in a pH stat assay. Emission spectra, lifetime analysis, acrylamide quenching, polarization, and anisotropy decay studies indicated that Tyr55 was located on the solvent-exposed surface of the protein, where the fluorophore experienced free rotation. Identical experiments done on DNStyr59PC indicated that Tyr59 was in a partially buried environment and the motion of the dansyl tyrosine group was hindered. The double-exponential decay of the fluorescence emission of N-acetyl-o aminodansyltyrosine ethyl ester (DNStyr) and the DNStyr derivatives of colipase was investigated with pH, temperature, solvent, and emission-resolved-lifetime experiments. The existence of excited-state processes was eliminated in both pH and emission-resolved-lifetime experiments, whereas temperature studies indicated either a rotational isomer or a differential solvent quenching mechanism for multiple decay kinetics. These experiments also showed that DNStyr was a sensitive probe of solvent polarity and viscosity, but not of pH. PMID- 2328242 TI - Identification and characterization of a novel linkage isomerization in the reaction of trans-diamminedichloroplatinum(II) with 5'-d(TCTACGCGTTCT). AB - The oligonucleotide 5'-d(TCTACGCGTTCT) reacts with trans diamminedichloroplatinum(II) to yield primarily trans-[Pt(NH3)2[d(TCTACGCGTTCT) N7-G(6),N7-G(8)]], containing the desired trans-[Pt(NH3)2[d(GCG)]] 1,3-cross link. A key element of the platination reaction is the use of low pH to suppress coordination at A(4). The product was fully characterized by pH-dependent NMR titrations, enzymatic degradation analysis, and 195Pt NMR spectroscopy. Interestingly, the 1,3-cross-linked adduct is unstable at neutral pH, rearranging unexpectedly to form the linkage isomer trans-[Pt(NH3)2[d-(TCTACGCGTTCT)-N3 C(5),N7-G(8)]]. This rearrangement product is more stable than the initially formed isomer and could be characterized by pH-dependent NMR titrations, enzymatic degradation analysis, liquid secondary ion mass spectrometric analysis of an enzymatically digested fragment, 195Pt NMR spectroscopy, and modified Maxam Gilbert footprinting experiments. By contrast, the 1,3-intrastrand cross-linked isomer rearranges during the course of both pH titration and enzymatic degradation experiments to form the 1,4-adduct. The equilibrium constant for this rearrangement is approximately 3, favoring the 1,4-adduct. Kinetic studies of the linkage isomerization reaction reveal t1/2 values for the first-order disappearance of the 1,3-intrastrand cross-linked isomer ranging from 129 (at 30 degrees C) to 3.6 h (at 62 degrees C), with activation parameters delta H not equal to = 91 +/- 2 kJ/mol and delta S not equal to = -58 +/- 8 J/(mol.K). Mechanistic implications of these kinetic results as well as the general relevance of this linkage isomerization reaction to platinum-DNA chemistry are briefly discussed. PMID- 2328243 TI - Mercury-induced DNA polymorphism: probing the conformation of Hg(II)-DNA via staphylococcal nuclease digestion and circular dichroism measurements. AB - Exposing native calf thymus DNA to increasing concentrations of Hg(ClO4)2 not only produces dramatic changes in its circular dichroism (CD) but results also in the decrease, and ultimate cessation, of endonucleolytic DNA cleavage by staphylococcal nuclease. Let r = [moles of added Hg(II)]/[mole of DNA base]: the conservative CD spectrum of the DNA B-form becomes nonconservative in appearance at 0.01 less than r less than 0.12 (resembling DNA in C-form geometry) and assumes the spectral characteristics of a left-handed DNA double helix at 0.12 less than r less than or equal to 1.0. DNA cleavage proceeds at or near the rates exhibited by untreated DNA at 0 less than r less than 0.08. At Hg(II) levels of 0.08 less than r less than 0.5, the rate of DNA hydrolysis decreases monotonically with increasing Hg(II) concentrations, and at r greater than 0.4, DNA cleavage ceases. Both the CD changes and the changes in the rate of DNA digestion are totally reversible upon the removal of Hg(II), at least up to r = 1.0, demonstrating that Hg(II) keeps all base pairs in register. For comparison purposes, native calf thymus DNA was also treated with methylmercury [CH3Hg(II)], an agent known to disrupt the secondary structure of DNA. The treatment yielded single-stranded methylmercurated DNA with preserved right-handed helix screwness. In addition, this DNA is digested by staphylococcal nuclease much more rapidly than double-stranded control DNA. Lastly, neither the CD nor the cleavage rate changes are reversible upon the removal of methylmercury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328244 TI - Sequence specificity of the deoxyribonuclease activity of 1,10-phenanthroline copper ion. AB - A statistical analysis of a data set composed of over 1600 scission events of DNA produced by the 2:1 1,10-phenanthroline-copper complex (OP-Cu) has demonstrated that the nucleotide 5' to the site of phosphodiester bond scission is a primary influence in the kinetics of cleavage at any sequence position. The scission was less affected by the 3' neighbor. For each of the sixteen possible dinucleotides, a kinetic parameter can be computed reflecting scission at the 3' nucleotide. When used to predict the scission pattern of a DNA sequence not part of the present data set, correlation coefficients of about 0.6 between predicted and observed patterns were obtained. PMID- 2328245 TI - In vitro biological activities of echinonectin. AB - Echinonectin (EN) is a 230-kDa extracellular matrix glycoprotein found in the hyaline layer of sea urchin embryos. Dissociated embryonic cells attached strongly to EN-coated microtiter wells in a centrifugal-based in vitro adhesion assay, suggesting that EN is one of the hyaline layer proteins to which cells adhere in vivo (Alliegro et al., 1988). The present study examines the molecular properties of that adhesion using monoclonal antibodies as probes to block cell attachment, and also demonstrates that EN possesses lectin activity. EN binds tenaciously to agarose-based chromatography resins, such as Sepharose. The sugar binding activity is associated with the polypeptide component of EN, and not with the carbohydrate moiety. Binding is inhibited with galactose and fucoidan, but not with glucose or locust bean gum. Although functional sites both for polysaccharide binding and for cell attachment are present on each subunit of the EN molecule, the sites appear to be functionally distinct because galactose and fucoidan are completely without effect on cell attachment in vitro. Proteolytic digestion of EN yields a highly limited set of immunoreactive peptides. Digestion with trypsin yields a 20-kDa fragment, chymotrypsin, a doublet at 20 kDa, and 20- and 23-kDa fragments with thermolysin. McAb's directed against these peptides block cell adhesion in vitro, suggesting that they possess the cell attachment domain of EN. This is supported by the observations that trypsin-digested EN is an effective substrate in adhesion assays and that adhesion to the tryptic fragments is also blocked by McAb's to the 20-kDa domain. PMID- 2328246 TI - Uptake of cholesterol by small intestinal brush border membrane is protein mediated. AB - Absorption of cholesterol by small intestinal brush border membrane from either mixed micelles or small unilamellar vesicles is protein-mediated. It is a second order reaction. The kinetic data are consistent with a mechanism involving collision-induced transfer of cholesterol. With micelles as the donor particle, there is net transfer of cholesterol while with small unilamellar vesicles as the donor, cholesterol is evenly distributed between the two lipid pools at equilibrium. The cholesterol absorption by brush border membrane from both mixed micelles and small unilamellar vesicles reveals saturation kinetics. Proteolytic treatment of brush border membrane with papain releases about 25% of the total membrane protein. As a result, the cholesterol uptake by brush border membrane changes from a second-order reaction to a first-order one. The reaction mechanism changes from collision-induced cholesterol uptake to a mechanism involving diffusion of monomeric cholesterol through the aqueous phase. The protein(s) released into the supernatant by papain treatment of brush border membrane exhibit(s) cholesterol exchange activity between two populations of small unilamellar vesicles. The supernate-protein(s) bind(s) the spin-labeled cholesterol analogue 3-doxyl-5 alpha-cholestane. PMID- 2328247 TI - Kinetic characteristics of calcium-dependent, cholinergic receptor controlled ATP secretion from adrenal medullary chromaffin cells. AB - Adrenal chromaffin cells secrete catecholamines (CA) and ATP in response to acetylcholine (ACh) and high [K+]o. The release process is relatively fast making it difficult to measure the early phase of the secretory response. Recently we were able to resolve the time course of the secretory response by measuring the release of ATP using luciferin-luciferase included in the extracellular medium. For the three secretagogues studied, ACh, nicotine and high [K+]o, the early phase of release followed a complex kinetics. Allowing for an initial delay of the secretory response, the kinetics could be described as the sum of two power exponential processes. Increasing the temperature from 23 to 37 degrees C induced a marked decrease in the two time constants needed to fit the early time course of the ATP secretion. The activation energies, estimated from Arrhenius plots, were approx. 20 and 16 kcal/mol for both phases of ATP release induced by either cholinergic agonists or high [K+]o. These results suggest that cholinergic receptor activation and membrane depolarization induce ATP (and CA) secretion through a common pathway. The initial delay in the onset of the secretory response decreased with increasing doses of secretagogue and with temperature. We propose that the delay preceding the actual onset of ATP release represents the time required for generation of intracellular second messengers. The effective concentration attained by these messengers depend apparently on both receptor occupancy by the agonist and the ensuing Ca2+ channel activation. PMID- 2328248 TI - Action of a homogeneous hydrogenation catalyst on living Tetrahymena mimbres cells. AB - Various conditions were tested in an attempt to hydrogenate the unsaturated fatty acids of living Tetrahymena mimbres with the homogeneous catalyst palladium di (sodium alizarine monosulfonate) without causing serious damage to the cells. Using a low (20 micrograms/ml) catalyst concentration in the external medium, hydrogenation of greater than 20% of surface membrane lipid double bonds were obtained, but hydrogenation of intracellular membranes was minimal. When exposed to H2, cells preincubated with inactive catalyst for several hours and visibly loaded with the catalyst lost viability as soon as hydrogenation exceeded trace levels. Material secreted by Tetrahymena into their medium effectively inhibited hydrogenation of added oleic acid, normally a good substrate. Mucus secreted by the cells, soluble proteins isolated from cell homogenates, bovine serum albumin, and cysteine were also inhibitory, but the inhibition could be overcome by employing higher catalyst concentrations. Although some enzymatic retroconversion of saturated lipids back to unsaturated lipids appeared to take place, the scale of the conversion was small, and further experimentation will be required to understand the mechanism involved. The selective hydrogenation of surface membranes achieved by these methods may be especially useful to those interested in fluidity effects on plasma membrane properties. PMID- 2328249 TI - Purification of octyl beta-D-glucopyranoside and re-estimation of its micellar size. AB - The commercial non-ionic detergent octyl beta-D-glucopyranoside is often contaminated by significant amounts of UV absorbing and/or ionic compounds that can associate with membrane proteins. Such impurities can be monitored by several techniques (i.e., spectrophotometry, size exclusion chromatography, and pH, conductivity, and surface tension measurements) and can be removed using mixed bed ion exchange chromatography. High performance size exclusion chromatography, dynamic light scattering, and ultracentrifugation have been used to re-estimate the size of micelles of octyl beta-D-glucopyranoside since previously published data varied over a wide range. Aggregation numbers were 27 to 100 for micellar molecular weights 8000 to 29,000. Direct physical methods that do not perturbate the sample indicated a large size for the micelles (hydrodynamic radius 23 +/- 3 A; Mr 22,000 +/- 3000; aggregation number 75 +/- 10 for a 34 mM aqueous solution). In contrast the chromatographic micellar size appeared to be smaller (hydrodynamic radius 15 +/- 1 A; Mr 8000 +/- 1000; aggregation number 27). This underestimation may be the result of adsorption and/or alteration of the micelles. PMID- 2328250 TI - Relation between membrane phospholipid composition, fluidity and function in mitochondria of rat brown adipose tissue. Effect of thermal adaptation and essential fatty acid deficiency. AB - Male weanling rats were maintained either at 28 degrees C (thermoneutrality) or at 5 degrees C (cold adaptation). During 9 weeks they were fed either a 2% hydrogenated coconut oil diet deficient in essential fatty acids or a diet containing 2% sunflower oil. The respective incidences of cold adaptation and of EFA deficiency on lipid composition of mitochondrial membranes from brown adipose tissue (BAT) were investigated. Using 1,6 diphenylhexatriene (DPH) as a probe, the parameters of membrane fluidity were estimated by steady-state fluorescence polarization measurements (rs) and by time-resolved fluorescence anisotropy decay (order parameter S). Cold acclimation induced a decrease of phosphatidylcholine to phosphatidylethanolamine (PC/PE ratio), an increase of the total fatty acid unsaturation index (T.U.). EFA deficiency had the same effect as cold on the PC/PE ratio, but decreased T.U. Cold adaptation induced a larger decrease of S than of rs, whereas EFA deficiency only increased rs and did not modify S. In liposomes prepared from mitochondrial lipids, rs values were smaller than in whole mitochondria. Both in cold-adapted and in EFA-deficient rats the variations of rs were correlated with lipid unsaturation. Comparison between BAT thermogenic activity, assessed by GDP binding and proportions of PE and PC showed a high correlation suggesting a change in the membrane occurring with the increase of mitochondrial activity that could be related to phospholipid composition rather than to membrane fluidity. PMID- 2328251 TI - Association of changes in lysophosphatidylcholine metabolism and in microsomal membrane lipid composition to the pulmonary injury induced by oleic acid. AB - Alterations in the lipid composition of lung microsomal membranes occur in oleic acid-induced respiratory distress. The marked decrease in the phosphatidylcholine/lysophosphatidylcholine molar ratio could be related with an altered metabolism of lysophosphatidylcholine in these membranes. Results revealed that the activity of phospholipase A increased whereas that of acyl CoA:lysophosphatidylcholine acyltransferase decreased. Microsomal lysophospholipase activity remained unchanged. On the other hand, the microsomal enzyme system involved in the de novo synthesis of diacylglycerol was impaired, and cholinephosphotransferase activity was lowered. These changes in the activity of some membrane-bound enzymes were not caused by changes in the membrane lipid fluidity since lipid structural order parameter (SDPH) did not change and neither did the major factors on which the fluidity depends. The possible significance of microsomal lipid alterations in the pathogenesis of respiratory distress induced by oleic acid is discussed. PMID- 2328252 TI - The cesium-induced delay in myoblast membrane fusion is accompanied by changes in isolated membrane lipids. AB - We have recently demonstrated that cesium ions delay the sharp decrease in both membrane conductivity and membrane permittivity of chick embryo myoblasts seen at fusion (Santini, M.T., Bonincontro, A., Cametti, C. and Indovina, P.L. (1988) Biochim. Biophys. Acta 945, 56-64). Analysis of the conductivity dispersion data (obtained in the radiowave frequency range) indicated that cesium delays fusion by about 30 h. We suggested that cesium is affecting both active ionic transport by blocking potassium channels as well as interfering with membrane lipid and/or protein charges. In the present study, we have investigated both the possible role of membrane lipids in myoblast fusion and the possible effects of cesium on these lipids. Our data indicate that lipid changes do occur in the isolated myoblast plasma membrane of controls during myogenic differentiation especially prior to fusion and that in cesium cultures these variations do not occur. These variations are in accordance with current membrane fusion theory. Specifically, there is a decrease in bilayer-stabilizing lipids (phosphatidylcholine) and an increase in bilayer-destabilizing ones (phosphatidylethanolamine and phosphatidic acid) and cholesterol during the fusion process. In addition, although slight, during fusion there appears to be a decrease in phosphatidylinositol which is believed to be involved in the inositol phosphate second messenger system. In cesium cultures, in which fusion is greatly delayed, the same lipid changes do not take place and those that are observed seem to reflect the fusion delay. PMID- 2328253 TI - Fractal filtering of channel data. AB - The fractal dimension of subsets of time series data can be used to modulate the extent of filtering to which the data is subjected. In general, such fractal filtering makes it possible to retain large transient shifts in baseline with very little decrease in amplitude, while the baseline noise itself is markedly reduced (Strahle, W.C. (1988) Electron. Lett. 24, 1248-1249). The fractal filter concept is readily applicable to single channel data in which there are numerous opening/closing events and flickering. Using a simple recursive filter of the form: Yn = w.Yn-1 + (1 - w)Xn, where Xn is the data, Yn the filtered result, and w is a weighting factor, 0 less than w less than 1, we adjusted w as a function of the fractal dimension (D) for data subsets. Linear and ogive functions of D were used to modify w. Of these, the ogive function: w = [1 + p(1.5-D)]-1 (where p affects the amount of filtering), is most useful for removing extraneous noise while retaining opening/closing events. PMID- 2328254 TI - High-performance liquid chromatographic analyses of porphyrins in hamster Harderian glands. AB - Porphyrin content and 5-aminolaevulinate synthase activity of the Harderian gland were measured in intact and gonadectomized male and female hamsters; porphyrin profiles were analysed by high-pressure liquid chromatography. The total porphyrin content of the two female groups was similar, but enzyme activity in females ovariectomised for 20 weeks significantly decreased. Intact males have low porphyrin content and enzyme activity, while in castrates (6 weeks) both increased to female levels. Protoporphyrin IX formed 93% of total porphyrins in intact females, compared with 70% of total porphyrins in intact males. The remainder in both sexes was chiefly penta- and hexacarboxylic porphyrins and coproporphyrin and (in females) Harderoporphyrin. Gonadectomy in either sex resulted in protoporphyrin levels intermediate between male and female values. PMID- 2328256 TI - Vitamin K-dependent carboxylase: effect of ammonium sulfate on substrate carboxylation and on inhibition by stereospecific substrate analogs. AB - (1) High concentrations of ammonium sulfate may stimulate the carboxylase activity of bovine liver microsomes about 10-fold. This effect results from an increase of the Vmax, whereas neither the apparent Km for a number of substrates nor the Ki for substrate analogs is affected. (2) The effect of ammonium sulfate was only found in substrates lacking the pro-sequence. No effect was measurable on the carboxylation of pro-PT28 and endogenous precursor proteins. (3) If the pro-fragment was added as a peptide not covalently bound to a carboxylatable substrate, the carboxylation thereof was only slightly affected and ammonium sulfate remained active as a stimulator of carboxylase activity. (4) S-MeTPT is a much stronger inhibitor of carboxylase activity than is R-MeTPT. (5) The inhibition of carboxylase by the methylated tripeptides is competitive and independent of the type of substrate. Also pro-PT28, which contains the full pro sequence, could be inhibited completely. (6) On the other hand the carboxylation of endogenous protein precursors could only be partly inhibited by the substrate analogs: even at high concentrations of S-MeTPT a residual endogenous substrate carboxylation of about 30% was left. PMID- 2328255 TI - Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors. AB - Thymidine phosphorylase (dThdPase) is an enzyme involved in pyrimidine nucleoside metabolism, but little is known about its physiological functions. We purified dThdPase from human placenta and used it for antibody preparation. The purified material appears as a single band at 55,000 dalton on sodium dodecylsulfate polyacrylamide gel electrophoresis. We obtained a specific antibody raised in rabbits that detected a single polypeptide with a molecular weight of 55,000 dalton in the post nuclear homogenates of several human tissues, on immunoblotting. Using the same technique, dThdPase was highly expressed in the liver, lung, spleen, lymph nodes and peripheral lymphocytes. Immunohistochemical staining revealed that macrophage-like cells contained a much higher amount of dThdPase than parenchymal cells in the liver and lung. dThdPase was found to be highly expressed in T- and B-cell-type malignant lymphoma cells, but low in lymphoblastic and myeloblastic leukemia cells. We also found that carcinomas in the stomach, colon and ovary contained higher amounts of this enzyme than non neoplastic regions of the tissues. These data suggest that dThdPase plays a role in proliferation and/or differentiation of leukocytes and in cancer proliferation. PMID- 2328257 TI - Hexokinase redistribution in vivo. AB - Heterogenous stock mice in addition to mice selectively bred to maximally differ in their severity of alcohol withdrawal seizures (withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP] were used to provide evidence in favor of the importance of the rapidly changing distribution of brain hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) (HK). An ischemic response at 15, 30, 60 and 120 s after killing showed a decreasing cerebellar cytosolic HK concentration of 31%, 15%, 14% and 10% while the cerebral concentrations were 23%, 13%, 13% and 14%, respectively. WSR and WSP mice given an acute i.p. dose of 4 g/kg of alcohol showed opposite HK responses. Cytosolic HK in WSR mice decreased 18.5%, while WSP mice showed an increase of 20.3% over paired saline injected controls. When ischemia was allowed to proceed in WSP mice following an in vivo alcohol treatment, cytosolic HK decreased in parallel to mice not given alcohol. These data suggest that alcohol can cause an HK redistribution in vivo which could play a role in the differing sensitivities of WSR and WSP mice to alcohol related seizures. PMID- 2328259 TI - An improved procedure for the isolation and purification of nicotinic acetylcholine receptor from Torpedo fuscomaculata electric organ. AB - The nicotinic acetylcholinergic receptor has been isolated and purified from extracts of the electric organ of the fish Torpedo fuscomaculata. The isolation procedure involves (a) a series of purification steps including preparation of membrane fragments, extraction of receptors with non-ionic detergents and chromatofocusing; (b) a novel fluorimetric titration assay. The purified receptor is isolated following a 9-fold purification with an overall yield of 12% and a specific activity of 4027 nM.g-1. Gel electrophoresis in the presence of sodium dodecylsulphate produced only one major band with molecular weight of 44,600 associated with the alpha-subunit. A comparison is made with other established procedures. Affinity chromatography on cobratoxin CNBr-Sepharose CL4B produced a 6.8-fold purification, 5% yield and 2900 nM.g-1 specific activity, while in ion exchange chromatography on DEAE Sepharose 6B gave a 4.7-fold purification, 3% yield and specific activity of 1988 nM.g-1. PMID- 2328258 TI - Metabolic changes induced by maximal exercise in human subjects following L carnitine administration. AB - In double-blind cross-over experiments, ten moderately trained male subjects were submitted to two bouts of maximal cycle ergometer exercise separated by a 3 day interval. Each subject was randomly given either L-carnitine (2 g) or placebo orally 1 h before the beginning of each exercise session. At rest L-carnitine supplementation resulted in an increase of plasma-free carnitine without a change in acid-soluble carnitine esters. Treatment with L-carnitine induced a significant post-exercise decrease of plasma lactate and pyruvate and a concurrent increase of acetylcarnitine. The determination of the individual carnitine esters in urine collected for 24 h after the placebo exercise trial revealed a decrease of acetyl carnitine and a parallel increase of a C4 carnitine ester, probably isobutyrylcarnitine. Conversely, acetylcarnitine was strongly increased and C4 compounds were almost suppressed in the L-carnitine loading trial. These results suggest that L-carnitine administration prior to high intensity exercise stimulates pyruvate dehydrogenase activity, thus diverting pyruvate from lactate to acetylcarnitine formation. PMID- 2328260 TI - Binding of hyaluronic acid to mammalian fibrinogens. AB - We have postulated that the interaction of hyaluronic acid (HA), an extracellular matrix glycosaminoglycan, with fibrin is important during the early stages of wound healing and inflammation (J. Theor. Biol. 119:219; 1986), and have demonstrated the specific binding of 125I-labeled HA to human fibrinogen (J. Biol. Chem. 261:12 586; 1986). To determine whether HA binding is limited to human fibrinogen, we tested the ability of fibrinogens from various mammalian species to bind 125I-HA using a dot-blot assay. Increasing amounts of fibrinogen were adsorbed to nitrocellulose, and incubated with 125I-HA in the presence or absence of a 100-fold excess of nonradiolabeled HA to assess specific binding. In three independent experiments, the amount of 125I-HA bound/mg fibrinogen was determined from the slope derived by linear regression analysis of specifically bound 125I-HA versus protein concentration. A Student's t-test was performed to determine whether the slopes were statistically greater than zero. HA binding was considered statistically significant when P less than 0.05 was obtained by this analysis. Rabbit and dog fibrinogens significantly bound HA in all three trials. Baboon fibrinogen demonstrated significant HA binding in two of three trials. Pig, sheep and goat fibrinogens bound HA significantly in only one of three trials, whereas horse, rat and cow fibrinogens did not bind HA significantly at all. We conclude that fibrinogen from mammalian species other than human can specifically bind HA. The ability of fibrinogen to bind HA appears to correlate with an evolutionary divergence that separated human, baboon, dog, rabbit and rat from cow, pig, horse, goat and sheep. PMID- 2328261 TI - Induction of fatty acid binding protein by peroxisome proliferators in primary hepatocyte cultures and its relationship to the induction of peroxisomal beta oxidation. AB - The induction of liver fatty acid binding protein (L-FABP) by the peroxisome proliferators bezafibrate and clofibrate was compared with the induction of peroxisomal (cyanide-insensitive) palmitoyl-CoA oxidation in cultured rat hepatocytes maintained on a substratum of laminin-rich (EHS) gel. This substratum was chosen because marked induction of both L-FABP and peroxisomal palmitoyl-CoA oxidation was effected by bezafibrate in hepatocytes supported on EHS gel, whereas only peroxisomal palmitoyl-CoA oxidation was induced in hepatocytes maintained on collagen-coated plates. In control cells on EHS, activity of peroxisomal palmitoyl-CoA oxidation remained stable, while L-FABP abundance declined with time, and L-FABP mRNA was undetectable after 5 days. In cultures exposed to bezafibrate or clofibrate, peroxisomal palmitoyl-CoA oxidation activity was induced earlier and more rapidly than L-FABP. When fibrates were withdrawn, peroxisomal palmitoyl-CoA oxidation declined rapidly, whereas L-FABP continued to increase. L-FABP induction was accompanied by a striking increase in mRNA specifying this protein. Tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase I, effectively doubled peroxisomal palmitoyl-CoA oxidation activity. However, tetradecylglycidic acid markedly inhibited fibrate induction of L-FABP and peroxisomal palmitoyl-CoA oxidation but, unexpectedly, did not prevent the fibrate-induced proliferation of peroxisomes. Maximal induction of both L-FABP and peroxisomal palmitoyl-CoA oxidation was produced at a bezafibrate concentration in the culture medium (0.05 mM) much lower than that of clofibrate (0.3 mM). Also, bezafibrate, but not clofibrate, inhibited [1-14C]oleic acid binding to L-FABP with a Ki = 9.5 microM. We conclude that hepatocytes maintained on EHS gel provide an important tool for investigating the regulation of L-FABP. These studies show that the induction of peroxisomal beta-oxidation and L-FABP by peroxisome proliferators are temporally consecutive but closely related processes which may be dependent on a mechanism distinct from that which leads to peroxisome proliferation. Furthermore, the mechanism of action of the more potent peroxisome proliferator, bezafibrate, may be mediated, in part, by interaction of this agent with L-FABP. PMID- 2328262 TI - Inhibition of glucose-regulated and heat shock protein induction by low temperature. AB - The present study evaluating induction of the major stress proteins in the subphysiological temperature range (25-33 degrees C) shows that none of the agents used could effectively induce the heat shock proteins (hsp) or the glucose related protein grp95 at low temperature. However, grp82 was still induced by some amino acid analogs and by glucose deprivation while certain oxygen-regulated proteins were still induced by hypoxia at 25 degrees C. Analogs were incorporated and protein turnover was increased at low temperature even though most stress proteins were not induced. Synthesis of hsps, but not that of grps, was induced if cultures containing analog-substituted proteins were shifted to 37 degrees C. Temperature dependence of hsp induction by arsenite showed a sharp threshold between 30 degrees C and 33 degrees C. Low temperature inhibition of induction points to the existence of a temperature-dependent mechanism operating within the normal physiological temperature range and may be a useful parameter in evaluating proposed mechanisms of stress protein regulation. PMID- 2328263 TI - N alpha-formylated and tert-butyloxycarbonylated Phe-(Leu-Phe)n and (Leu-Phe)n peptides as agonists and antagonists of the chemotactic formylpeptide receptor of the rabbit peritoneal neutrophil. AB - The various diastereomers of the N alpha-formylated(CHO) and tert butyloxycarbonylated (t-Boc) Phe-(Leu-Phe)n and (Leu-Phe)n methyl esters, where n = 1-2 and 1-3, respectively, have been newly synthesized and their physical properties described. The CHO-blocked peptides are all able to release beta glucosaminidase from rabbit peritoneal neutrophils in a concentration-dependent manner. There is a strong effect of primary structure and of chirality on their biology activity; lengthening the peptide chain distinctly increases activity in each series and within a series the activity decreases in the order: all-L greater than D-L much greater than all-D. Of the t-Boc protected synthetic precursors, the all-L isomers have definite but weak agonist activity; the agonist activity of the other isomers is equivocal or not detectable. All the t Boc peptides, however, are capable of acting as weak, specific antagonists. There is a dependence of antagonist activity on primary structure, but this is variable and contingent on the nature of the peptide. Similarly, an effect of chirality on antagonist activity, although present, also depends on the structure of the peptide. In the one instance directly tested, t-Boc-L-Phe-(D-Leu-L-Phe)2-OMe (OMe, methoxy) was found to be distinctly less active than the corresponding free acid. PMID- 2328264 TI - Characterization and synthesis of macromolecules by adult collateral ligament. AB - Bovine collateral ligament was found to have a water content of 67.5 +/- 2.5%, the tissue was highly collagenous containing 100.3 +/- 15.1 micrograms hydroxyproline/mg dry weight. Type I collagen was the major collagen present with small amounts of Type III and V. The hexuronate content of the tissue was found to be 2.62 +/- 0.40 micrograms hexuronate/mg dry weight of tissue. On incubation in vitro collateral ligament incorporated [35S]sulfate and [3H]acetate into proteoglycans and [3H]acetate into hyaluronate and glycoproteins. The rate of synthesis of proteoglycans by collateral ligament was shown on a weight basis to be greater than that of tendon but lower than that of articular cartilage. Analysis of the proteoglycans present in collateral ligament showed two populations of proteoglycans to be present. Approx. 20% of the total proteoglycans present were large chondroitin- and keratan sulfate-containing proteoglycans capable of forming aggregates with hyaluronate. The major species of proteoglycan present were small dermatan sulfate proteoglycans made up of a core protein with a molecular mass of 45,000 daltons with one dermatan/chondroitin sulfate glycosaminoglycan chain of 30,000 daltons attached. The N-terminal amino acid sequence of the core protein of this proteoglycan showed it to be analogous to the core protein of dermatan sulfate proteoglycan II. PMID- 2328265 TI - Inhibition of bovine dihydrofolate reductase and enhancement of methotrexate sensitivity by N4-(2-acetoxyethoxymethyl)-2-acetylpyridine thiosemicarbazone. AB - N4-(2-Acetoxyethoxymethyl)-2-acetylpyridine thiosemicarbazone (AATSC) belongs to a series of molecules known to have broad antimicrobial inhibitory activity. These molecules contain the 2-acetoxyethoxy moiety which could conceivably take up a conformation analogous to that of the ribosyl group. Moreover, the thiosemicarbazone moiety, when in the presence of a suitable enzymatic site, could mimic the triazine group, which is found in a number of antifolate drugs. AATSC, which has both bacterial inhibitory activity and water solubility, was accordingly evaluated for its antifolate activity against the bovine liver dihydrofolate reductase. AATSC is shown to be a fully uncompetitive inhibitor of that enzyme. Furthermore, AATSC enhances the activity of methotrexate. Such a potentiation could be useful for therapeutic purposes. PMID- 2328266 TI - Purification and characterization of a new arginine carboxypeptidase in human serum. AB - A carboxypeptidase capable of cleaving basic amino acids from synthetic peptide substrates is present in fresh human serum, and not in human heparinized plasma. Its activity is generated during the process of coagulation. Because of its unstability at room temperature and at 37 degrees C, we named it unstable carboxypeptidase (carboxypeptidase U). Carboxypeptidase U was partially purified from fresh human serum by chromatography on DEAE-cellulose and Mono-Q sepharose and was found to be a 435 kDa protein. We compared this enzyme with carboxypeptidase N, purified from human serum by a two-step affinity chromatography on arginine-Sepharose 4B, followed by ion-exchange chromatography on Mono-Q sepharose. Carboxypeptidase U cleaves hippuryl-L-arginine and hippuryl L-lysine, but at a different relative rate than carboxypeptidase N, and has no esterase activity on hippuryl-L-argininic acid. Its activity was inhibited by o phenanthroline, DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, CoCl2, 2 mercaptoethanol, dithiothreitol and 4-chloromercuribenzoic acid. These characteristics differentiate carboxypeptidase U from carboxypeptidase N and other known carboxypeptidases. PMID- 2328267 TI - Dielectrophoretic characterisation of Friend murine erythroleukaemic cells as a measure of induced differentiation. AB - Dielectrophoresis measurements, the study of the motion of particles in non uniform a.c. electrical fields, have been made on three cell lines (DS19, R1 and DR1) of Friend murine erythroleukaemia cells as a function of hexamethylene bisacetamide (HMBA) treatment. The effects of saponin treatment on R1 cells and neuraminidase on human red blood cells were also studied. It is shown that the dielectrophoretic behaviour can be interpreted in terms of cell surface charge and cell membrane conductivity effects. HMBA reduces the cell surface charge on all three cell lines, and in lines DS19 and DR10, where the cells are induced to differentiate, there is an increase in effective cell conductivity. This gain in conductivity is concluded to be associated with either an enhanced lateral electrophoretic motion of delocalised ions or of the polarisability of dipoles at the membrane surface. PMID- 2328268 TI - The undeveloped countries: biological psychiatry in India. PMID- 2328269 TI - Platelet adenylate cyclase and phospholipase C activity in posttraumatic stress disorder. AB - Adenylate cyclase and phospholipase C activity were examined in platelet membranes obtained from 19 male subjects with combat-related posttraumatic stress disorder (PTSD) and 35 age- and gender-matched healthy controls. Basal and forskolin-stimulated adenylate cyclase activity were significantly lower in the PTSD group whereas aluminum chloride plus sodium fluoride (AlCl3/NaF)- and prostaglandin E1 (PGE1)-stimulated responses were normal. There was no difference in phospholipase C activity between the two groups. The lower basal and forskolin stimulated adenylate cyclase responses replicate a previous report and suggest that PTSD may be associated with an abnormality of the catalytic subunit of the receptor-adenylate cyclase complex. PMID- 2328270 TI - Factors related to the presence of autoantibodies in patients with chronic mental disorders. AB - Serum samples from 307 patients with various chronic mental disorders were examined for the presence of several autoantibodies. Autoantibodies detected included antinuclear antibodies (ANA) in 122/307 (39.7%), rheumatoid factor (RF) in 23/307 (7.5%), anticardiolipin antibodies (anti-CL) in 23/304 (7.6%, IgM in 12 patients, IgG in 13 patients). Isolated cases with IgG anti-dsDNA, anti-Ro(SSA), and anti-Ro(SSA)/anti-La(SSB) were also identified. The analysis of data revealed that the aging process in patients studied contributed significantly to the incidence of ANA (p less than 0.0001) and RF (p less than 0.01). In addition, the chronic administration of chlorpromazine (CPZ) was associated with the presence of ANA (p less than 0.03) as well as with the presence of IgM and/or IgG anti-CL antibodies (p less than 0.003). Finally, the diagnosis of schizophrenia correlated with the presence of ANA (p less than 0.001). This study represents the autoantibody profile of patients with chronic mental disorders and emphasizes the multifactorial origin of autoantibody response in psychiatric patients. PMID- 2328271 TI - Fall in free thyroxine after ECT: real effect or an artefact of assay? PMID- 2328272 TI - Clonidine, cortisol, panic disorder, and depression. PMID- 2328273 TI - A theorem on amplitudes of thermal atomic fluctuations in large molecules assuming specific conformations calculated by normal mode analysis. AB - An exact theorem is proved and its implication is discussed. The theorem states that, if a large molecule, typically biological macromolecules such as proteins, undergoes small-amplitude conformational fluctuations around its native conformation in such a way that within the range of conformational fluctuations at thermal equilibrium the conformational energy surface can be approximated by a multidimensional parabola, then the mass-weighted mean-square displacement of constituent atoms is given by the sum of the contributions from each normal mode of conformational vibration, which in turn is proportional to the inverse of the square of its frequency. This theorem provides a firm theoretical basis for the fact hitherto empirically recognized in the conformational dynamics of, for instance, native proteins that very-low-frequency normal modes make dominant contributions to the conformational fluctuations at thermal equilibrium. Discussion is given on the implication of this theorem, especially on the importance of the concept of the low-frequency normal modes, even in the case where the basic assumption of the harmonicity of the energy surface does not hold. PMID- 2328274 TI - Oscillatory behavior of a water/oil interface system in response to current-clamp and voltage-clamp stimulation. AB - Oscillatory behavior in response to current-clamp and voltage-clamp stimulation was examined on a water/oil/water system consisting of an aqueous solution of sodium oleate as surfactant, a solution of 2,2'-bipyridine in nitrobenzene and an aqueous solution of sodium chloride. Stable oscillation was observed only when the strength of the stimulation lay within a specific range of values. PMID- 2328275 TI - A method for the experimental study of DNA conformational transitions in fibers. AB - The method proposed for the study of DNA conformational transitions is based on the proportionality, experimentally observed, between the length of a DNA fiber and the axial rise per nucleotide characterizing the molecular helix. Precise curves for the A-B and B-C transitions as a function of the relative humidity are obtained by using X-ray fiber data and measurements of fiber dimensions. It is thus shown that the A-B transition is a cooperative process between two different states, whereas the B-C transition can be considered as a progressive change of conformation. The present method is applied on two natural DNAs differing in base composition so that the effect of the nucleotide content on the conformational changes can be estimated. PMID- 2328276 TI - The diagram methods for the evaluation of exchange fluxes in membrane transport systems. AB - In this paper theoretical methods for the evaluation of fluxes of ligand exchange processes in a transporter-mediated membrane transport system are studied. The exchange process of a transport system is defined as a set of reactions of the transporters in the membrane that do not result in a complete turnover and must include the following consecutive sequence of steps: the binding of ligands from bath 1 and a subsequent release of bound ligands to bath 2 followed immediately by a binding of ligands from bath 2 and a subsequent release of bound ligands to bath 1. Thus, unlike the ordinary one-way cycles, the completion of an exchange process does not result in a net transport of ligands across the membrane. However, since it exchanges the ligands between the two baths, the exchange process of a transport system is closely related to the operational tracer flux of labelled ligands in the system. In this paper, both the numerical and the analytical procedures for the evaluation of exchange fluxes in any given biochemical diagram are discussed. In particular, we show that the exchange fluxes of a given kinetic diagram, like one-way cycle fluxes, can be expressed analytically in terms of the rate constants of the diagram with the use of either the original diagram or an expanded diagram. The diagram methods presented in this paper should be very useful in analyzing the mechanisms of transporter mediated transport systems when tracer flux data are available. PMID- 2328277 TI - A fluorescence temperature-jump study on Ca2(+)-induced conformational changes in calmodulin. AB - Calmodulin has been shown to alter its conformation so as to interact with a number of target proteins upon Ca2+ binding. A Ca2(+)-binding study of calmodulin was performed by monitoring the fluorescence of intrinsic tyrosine residues and the probe 1-anilinonaphthalene-8-sulfonate (ANS). ANS fluorescence was shown to reflect Ca2+ binding to both high- and low-affinity sites. On the one hand, tyrosine fluorescence was sensitive only to the high-affinity Ca2+ binding. Temperature-jump investigation of the ternary complex of Ca2(+)-calmodulin-ANS in combination with monitoring of ANS fluorescence demonstrated the kinetic characteristics of the conformational change. The relaxation process was attributed to Ca2(+)-induced conformational change and the rate constants of this process were evaluated. On the basis of the rate constants of the conformational change, a rapid response of calmodulin in Ca2+ signaling is suggested. PMID- 2328278 TI - Kinetic model for membrane transport. 1. Effects of membrane volume and partitioning kinetics. AB - Equations for the transport of solutes through a membrane are derived, taking into account both the membrane volume and the partitioning kinetics, and have been found to involve two rate constants for solute transport, namely, those corresponding to solute transport from the solution to the membrane (k1) and from the membrane to the solution (k2). The time course followed before partitioning equilibrium has been attained, which is usually ignored, is shown to depend strongly on the relative magnitudes of k1 and k2. PMID- 2328279 TI - Subunit hybridization studies of partially ligated cyanomethemoglobins using a cryogenic method. Evidence for three allosteric states. AB - Reaction of tetrameric hemoglobin with ligands at the four heme sites yields nine species that have structurally unique combinations of ligated and unligated subunits. Using hemoglobins where the ligated subunits contain cyanomethemoglobin, Smith and Ackers studied the dimer-tetramer assembly reactions in all nine of the partially ligated species (F. R. Smith and G. K. Ackers, Proc. Natl. Acad. Sci. U.S.A. 82 (1985) 5347). They found a third assembly free energy in addition to those of unligated hemoglobin and fully ligated cyanomethemoglobin. The observed distribution of the three assembly free energies among the ten species was found to be incompatible with the two-state mechanism of allosteric control (J. Monod, J. Wyman and J. P. Changeaux, J. Mol. Biol. 12 (1965) 81). The results indicated a mechanism of 'combinatorial switching' in which the binding free energies per site change with configuration of occupied sites and not just their number. In this study, we have confirmed the existence of three assembly free energies among the ten ligation species using a cryogenic method (M. Perrella and L. Rossi-Bernardi, Methods Enzymol. 76 (1981) 133). For one of the species we find a different free energy assignment from that reported by Smith and Ackers; for all other species we observe the same assignments as in earlier work. The revised distribution also requires a 'combinatorial' mechanism of allosteric switching among the three states. PMID- 2328280 TI - Side-chain interactions in the C-peptide helix: Phe 8 ... His 12+. AB - Previous studies have demonstrated that His 12 plays a major role in the pH dependent stability of the helix formed by the isolated C-peptide (residues 1-13 of ribonuclease A). Here, amino acid replacement experiments show that His 12+ stabilizes the C-peptide helix chiefly by interacting with Phe 8. The Phe 8 ... His 12+ ring interaction is specific for the protonated form of His 12 (His 12+) and the interaction is not screened significantly by NaCl, unlike the charged group ... helix dipole interactions studied earlier in C-peptide. Analogs of C peptide that are unable to form the Phe 8 ... His 12+ interaction show large increases in helix content for Phe----Ala and His----Ala. Therefore, the helical tendencies of the individual residues Phe, His, and Ala are important in determining the result of a replacement experiment. Since the side chains of Phe 8 and His 12 probably interact within the N-terminal helix of ribonuclease A, the existence of the Phe 8 ... His 12+ interaction in the isolated C-peptide helix adds to the evidence that the C-peptide helix is an autonomous folding unit. PMID- 2328281 TI - Structural and electrostatic effects on binding of trivalent cations to double stranded and single-stranded poly[d (AT)]. AB - We have measured the thermal melting profile for poly[d(AT)].poly[d(TA)] as a function of concentration of three trivalent cations: spermidine, me8spermidine, and hexammine cobalt(III). Using McGhee's (1976) theory of DNA melting in the presence of ligands, we have estimated association constants Kh, Kc and binding site sizes nh, nc for binding to double-helical (h) and single-stranded (c) polynucleotide. The results are as follows: (table; see text) The binding parameters for spermidine and hexammine cobalt(III) to double helical molecules agree fairly well with direct equilibrium dialysis measurements, and are in reasonable accord with predictions of counterion condensation theory. However, despite their identical charges, the three ligands bind to single-stranded DNA with quite different affinities. Estimates of the charge spacing of single stranded DNA suggest that poly[d(AT)] is less elongated in the presence of spermidine and hexammine cobalt(III) than it is when complexed with me8spermidine. PMID- 2328282 TI - Inactivation of the catalytic subunit of bovine cAMP-dependent protein kinase by a peptide-based affinity inactivator. AB - A peptide affinity inactivator, Ac-Leu-Arg-Arg-Ala-(BrAc)Orn-Leu-Gly, was used as a tool to probe for active site residues in the catalytic subunit of bovine cAMP dependent protein kinase. The peptide inactivated the catalytic subunit in an active site-directed and monophasic manner with a first-order rate constant of 0.03 min-1 and a dissociation constant of 675 microM. Studies with radioactive peptide indicated that approximately one equivalent of peptide was incorporated into each protein molecule. Protein sequencing identified the modified residue as Cys-199. A possible location for Cys-199 within the active site is suggested. PMID- 2328283 TI - Conformations of proline residues in membrane environments. AB - Although noted as hydrophilic residues with helix-breaking potential, proline residues are observed in putatively alpha-helical transmembrane (TM) segments of many channel-forming integral membrane proteins. In addition to the recognized property of X-Pro peptide bonds (where X = any amino acid) to occur in cis as well as trans isomeric states, the tertiary amide character of the X-Pro bond confers increased propensity for involvement of its carbonyl group in specific H bonded structures (e.g., beta- and gamma-turns) and/or liganding interactions with positively charged species. To examine this latter situation in further detail, we identified Leu-Pro-Phe as a consensus sequence triad based on actual occurrences of intramembranous Pro residues in transport protein TM segments. Accordingly, we have undertaken the synthesis of hydrophobic peptides with potential membrane affinity, of which t-butyloxycarbonyl-L-Ala-L-Ala-L-Ala-L-Leu L-Pro-L-Phe-OH (t-Boc-AAALPF-OH) is an initial compound. Partitioning of this peptide into model membrane environments composed of lipid micelles induces specific conformation(s) for the membrane-bound hexapeptide, as monitored by 75 MHz 13C-nmr spectral behavior of 13C-enriched Leu and Pro carbonyl carbons, and by 300-MHz 1H-nmr spectra of peptide alpha, beta, and aromatic protons. Data are interpreted in terms of an intramolecularly H-bonded inverse gamma-turn conformation in the membrane environment involving the Leu-Pro-Phe triad. The inherent structural instability of a Pro-containing segment in a TM helix due to the multiplicity of possible local conformations is discussed as a functional aspect of membrane-buried prolines in transport proteins. PMID- 2328284 TI - Construction, expression, and preliminary characterization of chimeric class mu glutathione S-transferases with altered catalytic properties. AB - An expression plasmid for isoenzyme 3-3 of rat liver glutathione S-transferase has been constructed from the cDNA clone pGTA/C44 and the pAS expression vector pMG27NS, and used for the efficient production of the enzyme in the Escherichia coli strain M5219. The plasmid has also been manipulated, through the use of synthetic linkers, to encode chimeric polypeptides in which short sequences of the closely related isoenzyme 4-4 have been substituted into the N-terminal and C terminal variable domains of isoenzyme 3-3. The chimeric polypeptides designated 4(9)3(208), 3(209)4(8), and 4(9)3(200)4(8) are expressed with varying degrees of efficiency in E. coli. The active dimeric holoenzymes 3-3, (4(9)3(208]2, (3(209)4(8]2, and (4(9)3(200)4(8]2 can be isolated. The spectroscopic and kinetic properties of the chimeric enzymes are significantly different than the native enzyme. PMID- 2328285 TI - The most highly amphiphilic alpha-helices include two amino acid segments in human immunodeficiency virus glycoprotein 41. AB - A search for highly amphiphilic alpha-helices has been made in a data base of protein sequences, using the helical hydrophobic moment as a criterion of amphiphilicity. The protein segments of largest hydrophobic moment have been analyzed. For the segments whose structures are known, they are in fact alpha helices. Two of the segments having very large hydrophobic moments are from the smaller C-terminal portion of the human immunodeficiency virus (HIV) envelope glycoprotein gp41. Also, among segments having large hydrophobic moments, but not among the most extreme, are lytic peptides such as melittin. Melittin seeks surfaces between polar and apolar phases, including the membrane-water interface. It is conceivable that the gp41 segments of extreme hydrophobic moment may participate in one of the membrane-related functions of the HIV virus. PMID- 2328286 TI - SV40 large T-antigen nuclear signal analogues: successful nuclear targeting with bovine serum albumin but not low molecular weight fluorescent conjugates. AB - The signal sequence of a nuclear-directed protein encodes the necessary information for targeting the attached proteins to the cell nucleus. The sequence/structural requirements for a functional transport signal were explored with a series of peptides derived from the simian virus 40 large T-antigen nuclear signal 126-134 (CPKKKRKVED-NH2, wild type) conjugated to bovine serum albumin (BSA) through an N-terminal Cys (1) with m-maleimidobenzoyl-N hydroxysuccinimide ester. Nuclear accumulation was virtually complete 15 min after microinjection into green monkey kidney cells (TC-7). Peptides with Asn, Orn, and Gln substituted for Lys128, the reverse wild-type peptide (DEVKRKKPC NH2) and the long 34-residue wild-type analogue (CYDDEATADSQHSTPPKKKRKVEDPKDFESELLS-NH2), were synthesized and conjugated similarly to BSA. The Orn peptide and the 34-residue wild-type analogue conjugated to BSA also transported to the nucleus but at a slower rate than 1. The reverse wild-type, Asn- and Gln-BSA conjugates of these signal analogues did not show transport to the nucleus after 6 h of incubation. In an effort to learn if such signal sequences would also target a small molecule such as a fluorescent tag to the nucleus, 1 fluorescently tagged with monobromobimane was prepared and microinjected into TC-7 cells. The peptide was distributed throughout the cell. These results support the notion that a positively charged residue at position 128 is needed for rapid nuclear transport and that the intracellular transport machinery has spatial recognition. The results with fluorophore-peptide conjugates suggest nuclear localization of these low molecular weight peptides will be difficult to attain even if attached to a functional nuclear localization sequence. PMID- 2328287 TI - Fluctuation and linkage relations in macromolecular solution. AB - It is shown in the appendix that the derivatives of the excess free energy of a macromolecule in solution, with respect to the activities of other solution components, lead to fluctuation and linkage relations among these other components. Solution fluctuation theory is used, but it is specialized to the fluctuations and correlations associated with the presence of a macromolecule, and is developed with a modified ensemble. The relations of the appendix are used to analyze the interaction of two solution components, A and B, with the macromolecule and with one another. Three cases are considered: (1) A and B are ligands that bind stoichiometrically to the macromolecule. This case reduces to Wyman's binding polynomial analysis. (2) A and B are two substances at high concentration that interact selectively with the macromolecule. (3) A is a species that binds stoichiometrically to the macromolecule, while B is a component at high concentration that interacts weakly with the macromolecule. PMID- 2328288 TI - Applications of simulated annealing to peptides. AB - We report the application of a new conformation searching algorithm called simulated annealing to the location of the global minimum energy conformation of peptides. Simulated annealing is a Metropolis Monte Carlo approach to conformation generation in which both the energy and temperature dependence of the Boltzmann distribution guides the search for the global minimum. Both uphill and downhill moves are possible, which allows the molecule to escape from local minima. Applications to the 20 natural amino acid "dipeptide models" as well as to polyalanines up to Ala80 are very successful in finding the lowest energy conformation. A history file of the simulated annealing process allows reconstruction and examination of the random walk around conformation space. A separate program, Conf-Gen, reads the history file and extracts all low-energy conformations visited during the run. PMID- 2328289 TI - Synergism through direct covalent bonding between agents: a strategy for rational design of chemotherapeutic combinations. AB - Self-assembling chemotherapeutic agents are mixtures of relatively nontoxic precursors that can combine chemically under physiological conditions to form products with greater cytotoxic and/or antimicrobial activity than either of the precursors. Combinations that form products more rapidly in or near the target (tumor, pathogen, virally infected cell) than in normal tissues will exhibit target-selective synergism, thus exhibiting an antitarget selectivity that is greater than the selectivities of the product (e.g., a hydrazone) and of either precursor (e.g., a hydrazine derivative or ketone) used singly. This paper describes the target-selective cytotoxic synergism of a cationic aldehyde (A) and a cationic acylhydrazine (B) containing a triarylalkylphosphonium moiety against Ehrlich ascites carcinoma cells (ELA) in culture, in addition to reviewing previous work on self-assembling cytotoxins. The synergism between A and B is carcinoma selective when the ELA cells (the target) are compared to CV-1, an untransformed African green monkey kidney epithelial line. Like tetraphenylphosphonium and rhodamine 123, which are selectively concentrated in ELA cells relative to CV-1, A, B and the hydrazone C resulting from their reaction are lipophilic delocalized cations that selectively inhibit ELA growth relative to CV-1 growth. The hydrazone C is more growth inhibitory than either A or B for both cell lines. A combination of A with an unreactive analogue of B and a combination of B with an unreactive analogue of A did not synergistically inhibit ELA proliferation. The degree of synergism is greater against the ELA cells than against the CV-1 cells. These data, together with hydrazone formation kinetics, suggest that A and B are both concentrated together selectively inside the ELA due to the transmembrane potentials, reacting inside the ELA cells at a higher velocity than inside the CV-1 cells to form the more growth-inhibitory hydrazone C. PMID- 2328290 TI - Cyclic pentapeptides as models for reverse turns: determination of the equilibrium distribution between type I and type II conformations of Pro-Asn and Pro-Ala beta-turns. AB - Cyclic pentapeptides are excellent models for reverse turns and have been used extensively in our laboratory to explore the influence of different amino acid sequences on turn preference. This paper is divided into two parts: In the first, we review our previous studies of cyclic pentapeptides. We summarize work that demonstrates the range of conformations possible within the cyclic pentapeptide backbone, the importance of sequence chirality in determining the backbone fold, and the utility of these cyclic pentapeptides as models for various turns. In the second, we present new results on two cyclic pentapeptides that contain beta turns with Pro-Ala or Pro-Asn sequences in the i + 1 and i + 2 positions. By stereochemical criteria, a type I beta-turn is expected to be preferred by such L L sequences. On the other hand, in proteins Asn occurs frequently in the i + 2 position of type II turns. We asked whether the same propensity would be manifest in an isolated model peptide, and if so, what the interactions were that influenced the relative stability of the type I and type II turns. To address these questions we have compared the conformational behavior of two peptides: cyclo(Gly-Pro-Ala-D-Phe-Pro) and cyclo(D-Ala-Pro-Asn-Gly-Pro). From previous studies, we anticipated that both peptides would contain an inverse gamma-turn and a beta-turn which consisted of either Gly-Pro-Ala-D-Phe or D-Ala-Pro-Asn-Gly in positions i to i + 3, respectively. Nuclear magnetic resonance analysis confirms this overall backbone conformation. Furthermore, quantitative nuclear Overhauser effect measurements in combination with molecular dynamics simulations and torsionally-forced energy minimizations have enabled us to determine that both type I and type II beta-turns are present in equilibrium in these peptides. The introduction of Asn in position i + 2 shifts this equilibrium significantly towards type II. We have done preliminary assessment of the possible side chain/backbone conformations that contribute to the shift in populations. PMID- 2328291 TI - Fourier transform infrared spectroscopy for the characterization of a model peptide-DNA interaction. AB - To better understand the structural basis of protein-DNA interactions, the conformational changes that accompany these interactions need to be described. In order to develop a methodological approach to this problem, Fourier transform infrared spectroscopy (FTIR) with derivative resolution enhancement has been used to identify conformational changes that occur when a 29-residue synthetic peptide binds nonspecifically to heterogeneous cellular DNA in aqueous solution. The peptide sequence was chosen de novo, in order to rationally design a peptide model that would allow the relationship between DNA binding and the stability of protein secondary structure to be studied. Peptide at a concentration of 100-200 microM produces 50% saturation of heterogeneous phage DNA sequences as well as of short synthetic oligonucleotides. FTIR spectra reveal significant changes in peptide and DNA upon binding. Second-derivative spectra resolve the amide I band of native peptide into components located at 1627 (beta-strand), 1658 (alpha helix), and 1681 (turn or beta-strand) cm-1, with a distinct shoulder at 1647 cm 1 (disordered structure). Assignment of the 1681 cm-1 vibration to a turn conformation is supported by uv CD studies, which indicate significant amounts of turn structure in unbound peptide. Ultraviolet CD also confirms the existence of disordered and beta-strand regions in the free peptide. Upon interacting with DNA the band at 1681 cm-1 (turn) is no longer seen; a new band appears at 1675 cm-1; the 1627 cm-1 band (beta-strand) is considerably reduced in intensity; the position of the alpha-helical (1658 cm-1) component remains unchanged; the shoulder at 1647 cm-1 (disorder) disappears. The new vibration at 1675 cm-1 is characteristic of beta-strand structures. The asymmetric stretch (vAS) of the DNA phosphates shifts from 1223 (unbound) to 1229 cm-1 (bound); the relative intensities of vAS and the PO2- symmetric stretch (vS) are altered upon peptide binding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2328292 TI - Autoxidation of ascorbic acid catalyzed by a semisynthetic enzyme. AB - The semisynthetic enzyme 6 was prepared by alkylation of the cysteine-25 sulfhydryl group of papain with the bipyridine 5 and was shown to stoichiometrically bind copper ion; 7 catalyzed the autoxidation of ascorbic acid derivatives with saturation kinetics approximately 20-fold faster than a model system using 3-Cu(II). PMID- 2328293 TI - Synthesis of analogues of peptide YY with modified N-terminal regions: relationships of amphiphilic secondary structures and activity in rat vas deferens. AB - Peptide YY (PYY) not only has distinct sequence homology with neuropeptide Y (NPY) and avian pancreatic polypeptide (APP), but it also exhibits both NPY- and APP-like biological activities. We synthesized two analogues of PYY, A1 and A2, with modified N-terminal regions, and compared their chemical and biological properties to those of PYY and the C-terminal fragment of PYY, (13-36)PYY. This study shows that there is a good correlation between the stability of amphiphilic alpha-helical structure and the biological activity of these peptides. A CD study of (13-36)PYY in mixed H2O and trifluoroethanol (TFE) solutions indicated a significant increase in alpha-helical segments (26-79%) with increasing TFE proportions. Since the fragment (13-36)PYY had potent activity in the rat vas deferens (RVD) assay, the secondary structure is possibly required on the RVD cell surface receptors. The analogues, A1 and A2, were designed to increase the stability of the alpha-helical structures by incorporation of modified N-terminal regions. The CD studies and the RVD assays of A1 and A2, suggest that the amphiphilic alpha-helical structures are stabilized by intramolecular hydrophobic interactions with the N-terminal regions and/or by intermolecular hydrophobic interactions in the self-association process, and subsequently potentiate the activities of the peptides compared to those of PYY and (13-36)PYY. PMID- 2328294 TI - Structural dependence of oligonucleotide photooxidation. AB - Oxidative photosensitization was used to characterize the conformational dependent reactivity of various structures formed by oligonucleotides 14-15 nucleotides in length. The rate and product composition from a single hit process was analyzed using quantitative ion exchange chromatography under native and denaturing conditions. The primary damage incurred under aerobic acetone sensitization was base oxidation that, in turn, would induce strand scission upon a secondary treatment with piperidine. The reactive intermediates of this process were not consistent with diffusible radical species or singlet oxygen, as indicated by isotope and quenching studies. Derivatization was most likely initiated through a type I photoprocess with a direct interaction between DNA bases and excited state acetone preceding an irreversible oxidation step. This dominant reaction demonstrated no obvious sequence or site specificity for initial modification; the relative reactivity among the oligonucleotides did not correspond to any simple trend of base composition or near neighbor analysis. Likewise, the steric requirements of base modification allowed for similar rates of oxidation for single-strand, helical, and aberrant forms of DNA. Hybridization of the most reactive oligonucleotides, however, did suppress their relative single-strand vs double-strand reactivity by as much as fourfold. PMID- 2328295 TI - Synthesis and structural stability of helichrome as an artificial hemeproteins. AB - A detailed procedure is described for the synthesis of helichrome, which is the first successful example of polypeptide-based artificial hemeprotein. The segment synthesis-condensation approach used for the assembly of small proteins has proven to be extremely useful for protein mimetics as well. The final deprotection was performed using the TMSOTf-thioanisole method instead of the less-convenient hydrogen fluoride method. The unfolding transition of the alpha helical conformation of helichrome induced by guanidine hydrochloride was studied to understand the stability and dynamics of the folded structure. The resulting parameters (C0.5 = 5.2 M and delta GH2O = -4.4 kcal mol-1) characterizing helichrome denaturation were comparable to that of native globular proteins. PMID- 2328296 TI - A new approach to pharmacokinetic parameters: estimation of cefuroxime during haemodialysis. AB - A linear three-compartment model is proposed as a means of estimating disposition and extracorporeal elimination pharmacokinetic parameters during haemodialysis. It was created by connecting a compartment, corresponding to the amount of drug present in the dialysis cell, to the central compartment of the standard two compartment model from which elimination would normally take place. The transfer rate constants between the central compartment and the 'dialysis cell' and vice versa were given in terms of the plasma flow, central compartment volume, and volume of plasma contained in the dialysis cell, and thus cannot be considered to be independent parameters. The product of the rate constant for elimination from the dialysis cell, k30, and the plasma volume within the cell was used to quantify the extracorporeal elimination and termed intrinsic dialyser clearance, CLint,D. The model was used to interpret the plasma level curves obtained after administering 750 mg cefuroxime by IV bolus to a group of patients undergoing haemodialysis. The distribution parameters estimated by non-linear regression were similar to those given in the literature; however, in five of the twelve cases, no estimate of cefuroxime elimination from the central compartment (k10) could be derived. On the other hand, the estimates of the elimination rate constant (k30) from the deep peripheral compartment were greater than the values given in the literature, ranging from 50.6 h-1 to 151.0 h-1 and CLint,D ranging from 3.1 h-1 to 8.90 l h-1. The error in measuring the flow of plasma which reaches the dialyser, its influence upon the estimation of the model parameters and the relationship between the parameters themselves and those customarily used in the study of drug haemodialysis are all discussed. PMID- 2328297 TI - The disposition of cytosine arabinoside and its metabolite after single doses to rabbits. AB - Cytosine arabinoside (ara-C) is rapidly deaminated in vivo to ara-U by cytidine deoxycytidine deaminase. The purpose of this study was to determine the contribution of the deamination pathway to the overall clearance of ara-C after a single dose to rabbits, as well as to determine the pharmacokinetics of ara-U itself. Male rabbits were cannulated in the marginal ear vein and received a single IV bolus dose (50 mg kg-1) of either ara-C (n = 10) or ara-U (n = 10). Blood samples were collected for up to 24 h. One week later, the rabbits received the opposite treatment. Plasma samples were analyzed by reversed-phase HPLC. The plasma clearance of ara-C (8.16 +/- 2.43 ml min-1 kg-1) was significantly higher than the clearance of ara-U (5.66 +/- 2.59 ml min-1 kg-1). The volume of distribution of ara-C was 0.64 +/- 0.16 l kg-1 (mean +/- SD) and was significantly smaller (p less than 0.05) than that of ara-U (1.22 +/- 0.70 l kg 1). As a result, the elimination rate constant of ara-C was significantly larger than that of ara-U (0.602 +/- 0.097 h-1 vs 0.258 +/- 0.05 l h-1). In the rabbits that received both treatments (n = 7), the fraction of the ara-C dose metabolized to ara-U (fm) was 0.53 +/- 0.20. Qualitatively, the pharmacokinetics of ara-C and ara-U resemble those in humans. This study provides the basis for further work into the modulation of ara-C disposition either by ara-U or other agents. PMID- 2328298 TI - Dose dependent pharmacokinetics of N-acetylcysteine after oral dosing to man. AB - The pharmacokinetics after oral administration of 200, 600 or 1200 mg of N acetylcysteine (NAC) were studied in 10 healthy subjects. Normalized maximal plasma concentration was significantly higher after a 600 mg dose than after a 200 mg dose. Bioavailability of NAC significantly increased with increasing dose. Time for maximal plasma concentration also increased with increasing dose. The observations can be explained by a capacity-limited presystemic elimination of NAC. In an extension of the study, 600 mg of NAC was given twice a day for 5 days and the plasma concentrations were followed after the morning dose on day 6. No differences in the pharmacokinetic parameters were observed in comparison with the single 600 mg dose. This indicates that the beneficial clinical effects observed after repeated dosing can not be ascribed to an accumulation of NAC in plasma. PMID- 2328299 TI - Influence of food on the bioavailability of diltiazem and two of its metabolites following the administration of conventional tablets and slow-release capsules. AB - The influence of food on the bioavailability of a conventional tablet and of a slow-release capsule of diltiazem was investigated in two separate groups of 24 healthy volunteers in two open crossover studies. Diltiazem, as a conventional tablet (2 x 30 mg, first group) or as a slow-release capsule (120 mg SR, second group), was administered in a fasting condition and 30 min after a breakfast of 784 kcal (23 per cent proteins, 55 per cent lipids, and 22 per cent of carbohydrates). Multiple blood samples were withdrawn during the next 24 h and diltiazem, desmethyldiltiazem, and deacetyldiltiazem were assayed by HPLC. Neither the rate of absorption, assessed by the rate constant of absorption, the peak plasma concentration, and the time required to reach the peak, nor the amount of drug reaching the systemic circulation, assessed by the area under the plasma concentration time curve (AUC infinity) were influenced by food, and that independently of the formulation. Compared to the fasting experiment, food did not affect either the rate of formation or the AUC infinity of desmethyldiltiazem or deacetyldiltiazem. The results of the present study show that the relative bioavailability of the single dose of diltiazem administered as a slow-release capsule is significantly higher (69 per cent) than that estimated after the administration of diltiazem in a conventional tablet. It was concluded that food does not influence the bioavailability of diltiazem administered as a conventional tablet or as a slow-release formulation. PMID- 2328300 TI - Pharmacokinetic analysis of absorption and metabolism of dopamine and a dopamine prodrug in dogs. AB - Pharmacokinetic compartment models were constructed to describe the absorption and metabolism of dopamine (DA) and DA prodrug, N-(N-acetyl-L-methionyl)0,0-bis eth-oxycarbonyl) dopamine(1). Plasma concentrations of DA, DA-SO4, and DOPAC after oral administration of DA to dogs, were analysed using the pharmacokinetic model assuming the contribution of first-pass metabolism for the formation of DA SO4 and DOPAC. Though plasma concentration of DA was quite different from that of DA-SO4 or DOPAC, these data were simultaneously analysed with a good fitting curve. The apparent absorption rate constant of DA(K1) was proved to be much smaller than the apparent formation rate constants of DA-SO4(K2) or DOPAC(K3). It was found that the compartment model is useful for the evaluation of absorption and metabolic inactivation of DA. Plasma concentration of DA, N-(N-acetyl-L methionyl)dopamine(2), DA-SO4, and DOPAC after oral administration of 1 were simultaneously analysed using the compartment model including the first-pass metabolism and two-fraction dissolution process. Good fitting curves were obtained. The apparent formation rate constant of 2(K4) is larger than that of DA SO4(K5) or DOPAC(K6); thus it was shown that two protective groups of 1 reduced the metabolism of DA and 2 specially played an important role to the reduction of first-pass metabolism. From these results, it was found to be possible to give a pharmacokinetic interpretation for the mechanism of reduction of first-pass metabolism of DA. PMID- 2328301 TI - Bioavailability of a new sustained-release theophylline capsule in fasted and non fasted healthy subjects: single and multiple dosing studies. AB - Eighteen healthy, non-smoking, adult volunteers participated in single and multiple dose three-way crossover studies to evaluate a sustained-release, pellet filled capsule of theophylline, Austyn. The effect of food on the bioavailability of the sustained-release capsule was investigated by administering 300 mg single doses of Austyn, with a high-fat meal and without food and a divided 300 mg dose of the reference product Elixophyllin elixir, given after fasting. Plasma theophylline concentrations were measured by fluorescence polarization immunoassay (FPIA) which had been validated against HPLC. The single dose study data showed that there were no significant differences (n = 18, ANOVA, p greater than 0.05) between the three regimens with respect to AUC0-infinity values (mg h l-1), (mean +/- SD); Elixophyllin fasting = 97.1 +/- 33.7, Austyn with food = 90.9 +/- 31.3, Austyn fasting = 91.2 +/- 33.8. Similarly, multiple dosing with rapid-release Nuelin tablets, Austyn capsules, and sustained-release Theo-Dur tablets demonstrated that there were no significant differences between regimens with respect to AUC0-24h, AUC0-12h, and AUC12-24h values calculated from the steady-state concentrations (5th day, 24 h sampling). However, the percentage fluctuation at steady-state over the total blood sampling period was significantly less for treatment with the sustained-release capsule. Austyn, compared with the sustained-release tablet, Theo-Dur (Austyn = 36.7 +/- 13.7 per cent, Theo-Dur = 53.1 +/- 14.1 per cent). The results of the single and multiple dose studies indicate that Austyn capsules demonstrate complete bioavailability, and good controlled release characteristics not influenced by concomitant intake of a high-fat meal and with no evidence of dose dumping. PMID- 2328302 TI - Mean residence time and the meaning of AUMC/AUC. PMID- 2328303 TI - Absorption of doxycycline from a controlled release pellet formulation: the influence of food on bioavailability. AB - A three-way crossover study was performed to compare the bioavailability of a new pelletised doxycycline product administered either with food or without food and a reference product taken without food. Four different methods were used to calculate pharmacokinetic parameters from the data. The sums of squares, Akaike's Information Criterion (AIC), and the ranges for the parameters obtained were used for comparison. Good fits to the data were obtained when all four methods were used, each with a lag time. The two compartment open model was the most efficient method for describing the data. The one compartment open model was the least efficient, particularly with respect to predicting the peak concentration of doxycycline in plasma. All the models gave similar rank order results with respect to bioavailability differences between the three treatments. Analysis of the data by different methods suggests that pelletised doxycycline is bioequivalent to the reference product when taken in the absence of food. A standardized feeding regimen affected the rate, but not extent of absorption of doxycycline from the pelletised formulation. PMID- 2328304 TI - Diphenhydramine kinetics following intravenous, oral, and sublingual dimenhydrinate administration. AB - Eight healthy volunteers received 50 mg of dimenhydrinate, a theoclate salt of diphenhydramine, orally, sublingually, and intravenously on three separate occasions in random sequence. Plasma diphenhydramine concentrations during 12 h after each dose were measured by gas-liquid chromatography with nitrogen phosphorous detection. Mean peak plasma concentrations after sublingual administration were slightly lower than after oral dosage (38.3 vs 47.8 ng ml-1), and the time of peak concentration was similar (2.6 vs 2.3 h after dose). These differences did not reach statistical significance. The mean total area under the plasma concentration-time curve (AUC) for sublingual administration was slightly but not significantly smaller than after oral dosage (221 vs 270 h ng ml-1). Systemic availability of diphenhydramine after sublingual dimenhydrinate, measured by the ratio of oral AUC to intravenous AUC, was slightly less than after oral dimenhydrinate (0.58 vs 0.69, NS), and both were significantly less than 1.0. Thus sublingual and oral administration of dimenhydrinate result in comparable, but incomplete, systemic availability of diphenhydramine. PMID- 2328305 TI - Multiple-dose propranolol administration does not influence the single dose pharmacokinetics of quinapril and its active metabolite (quinaprilat). AB - To evaluate the influence of multiple dose propranolol administration on the single dose pharmacokinetics of quinapril and its active metabolite, quinaprilat, a drug-drug interaction study was performed in ten healthy volunteers. Each subject received a single 20 mg quinapril oral dose on Days 1 and 16 of the study. Oral propranolol doses of 40 mg BID were initiated on Day 3, titrated gradually to 80 mg TID by Day 10, and continued at 80 mg TID through Day 17. Comparable mean quinapril pharmacokinetic parameter values as well as comparable mean quinaprilat pharmacokinetic parameter values determined following quinapril administered alone and following quinapril administered with propranolol, indicate that propranolol does not alter the single dose pharmacokinetics of quinapril or quinaprilat. PMID- 2328306 TI - Influence of lovastatin on the pharmacokinetics, toxicity and immunologic response of cyclosporine in the obese Zucker rat. AB - The combined use of lovastatin, a hypolipidemic agent effective in the reduction of cholesterol levels, and the lipophilic immunosuppressant, cyclosporine, was studied in the obese rat model. Pharmacokinetics, immunosuppressive activity, lipid levels, and creatinine clearances were compared between groups administered drug-free vehicle, lovastatin or cyclosporine alone, or concomitant cyclosporine and lovastatin. All groups were pre-treated with either oral lovastatin 2.5 mg kg 1 day-1 or propylene glycol vehicle for 1 week. Although no differences in renal function were observed in rat groups administered cyclosporine or lovastatin alone, there was a significant reduction in baseline creatinine clearance following combination therapy compared to placebo controls (70 +/- 18 vs 121 +/- 16 per cent of baseline; p less than 0.05). No differences in trough cyclosporine concentrations were observed between groups. Similarly, mean areas under the whole blood concentration-time profiles were not significantly different with or without concomitant lovastatin (61823 +/- 27295 vs 41470 +/- 10312 ng h ml-1; p = 0.13). No differences in systemic clearance or volume of distribution of parent cyclosporine were observed with combination therapy. Furthermore, lipid levels and T-lymphocyte activity were unchanged with the addition of lovastatin. Per cent increases in creatine kinase were significantly correlated with percentage drop in baseline renal function, suggesting the development of rhabdomyolysis. The present data support the interaction between cyclosporine and lovastatin observed clinically, resulting in acute renal dysfunction. Caution should be exercised in their combined use. PMID- 2328307 TI - Intramuscular administration of atropine in the rat: jet spray versus conventional needle injection. AB - The characteristics of atropine plasma levels after jet spray injection were compared to those after conventional needle injection (i.m.) in 12 male rats, six per group. Blood samples were sequentially collected from the tip of the tail over a 7h period. Injection of atropine sulfate (8.0 mg kg-1) using the jet spray resulted in mean peak plasma levels of 650 ng ml-1 (95 per cent C.I. = 90) compared to 488 ng mg-1 (95 per cent C.I. = 64) using a conventional needle. Times to reach maximum concentration were 30 min (95 per cent C.I. = 12) and 58 min (95 per cent C.I. = 6) for the jet spray and needle, respectively. Histopathologic examination (5 days post-injection) of target muscle showed that minimal fiber damage resulted from using the low pressure setting on the jet spray. The results suggest that the jet spray may offer a means of increasing the antidotal benefit over that achieved with conventional techniques using presently available therapeutic formulations for acetylcholinesterase poisoning. PMID- 2328308 TI - Effects of dose and sex on the pharmacokinetics of piroxicam in the rat. AB - The effects of dose and sex on the pharmacokinetics of piroxicam were studied in the rat. Piroxicam was administered intravenously at doses of 0.50 and 5.0 mg kg 1 to male and female rats. Plasma drug concentrations were determined by a highly sensitive high-performance liquid chromatographic technique. Non-compartmental pharmacokinetic parameters were calculated by area/moment analysis. A prolonged terminal half-life averaging 13.3 h in male rats and 40.8 h in female rats was observed. Dose had no effect on the disposition of piroxicam. The sex of the rat, however, had a marked effect on piroxicam pharmacokinetics, with mean total clearance differing three-fold from 0.0184 l h-1 kg-1 in male rats to 0.00622 l h 1 kg-1 in female rats. The free fraction of piroxicam in serum was greater in male rats than in female rats owing to a higher association constant for piroxicam binding to female rat serum proteins. Free piroxicam clearance differed approximately two-fold with mean values of 0.764 l h-1 kg-1 and 0.418 l h-1 kg-1 in male and female rats, respectively. Thus, protein binding partially explained the sex-dependent disposition of piroxicam. However, sex-dependent metabolism of the drug also appears to be a major determinant of sex-related differences in piroxicam pharmacokinetics. Steady-state volume of distribution was unaffected by sex. Half-life and mean residence time were three-fold greater in female rats owing to the three-fold lower clearance value compared to male rats. PMID- 2328309 TI - Pharmacokinetics of the acetylcholinesterase oxime reactivator, HI-6, in rhesus monkeys (Macaca mulatta): effect of atropine, diazepam, and methoxyflurane anesthesia. AB - The pharmacokinetics of the bispyridinium oxime HI-6 (CAS reg. no. 34433-31-3; 1 (((4-aminocarbonyl)pyridinio)methoxy)methyl)-2-[hydroxy i mino)methyl)- pyridinium dichloride) was investigated in rhesus monkeys (Macaca mulatta). The effects of methoxyflurane anesthesia, administration of atropine with and without diazepam were determined on the serum half-life (t1/2), clearance rate (CL), and the volume of distribution (Vd) following intramuscular (IM) administration of HI 6 (30 mg kg-1). The control t1/2, CL and Vd of HI-offere 27 min, 8.6 ml min-1 kg 1 and 0.34 l kg-1, respectively. These parameters were unaffected by the co administration of either atropine (0.5 mg kg-1, IM) or atropine and diazepam (0.5 mg kg-1, IM + 0.2 mg kg-1 IV, respectively). Methoxyflurane anesthesia resulted in a significant increase in the HI-6 t1/2 to 61 min concomitant with a decrease in the CL to 4.1 ml min-1 kg-1 with no change in the Vd. The increase in the t1/2 of HI-6 in methoxyflurane anesthetized monkeys is probably the result of a decrease in the clearance rate and, thus, excretion of HI-6 by the kidneys. PMID- 2328310 TI - Absorption and disposition of a new low-dose combination formulation of hydrochlorothiazide and triamterene. AB - Two studies are reported that assess the bioequivalence of a new half-strength drug combination containing 25 mg hydrochlorothiazide and 37.5 mg triamterene compared to a full-strength formulation containing 50 mg hydrochlorothiazide and 75 mg triamterene. The first study (I) compared the absorption and disposition of the two drugs after administration of two tablets of the half-strength product as a single dose compared to a single dose of the full-strength product. The second study (II) assessed the bioavailability of the new product given as a single tablet on two occasions separated by an interval of 12 h compared to the full strength product given as a single dose. Urine parameters in the first study indicated bioequivalence of the half-strength to the full product for both rate and extent of absorption. When given in divided doses, the half-strength product demonstrated bioequivalence to the full-strength product for extent of absorption. Additional data from the second study suggest that absorption of triamterene is greater when given in smaller divided doses and when given at night. PMID- 2328311 TI - First-pass metabolism of acetaminophen in rats after low and high doses. AB - The first-pass metabolism of acetaminophen was examined in rats after the administration of 15, 30, 150, and 300 mg kg-1 doses by intra-arterial, intravenous, portal vein, and oral routes. Plasma concentrations of acetaminophen and its two major metabolites, acetaminophen glucuronide and acetaminophen sulfate, were measured for about 5 h after drug administration. The first-pass effect after oral administration (oral extraction) was extensive (Eo = 0.34-0.50) at all doses administered. Calculation of the relative contribution of the gastrointestinal tract, liver, and lung to the oral extraction of acetaminophen indicated that the major contribution was due to the gastrointestinal tract at all doses studied (Eg = 0.33-0.50). At higher doses (150 and 300 mg kg-1) clearance was lower possibly due to the saturation of acetaminophen sulfate formation. However, even at these high doses, the contribution of the gastrointestinal mucosa to the oral extraction remained unchanged. Therefore, it appears that the apparent dose-dependent characteristics of acetaminophen metabolism may be due to the saturation of acetaminophen sulfate formation in the liver. PMID- 2328312 TI - In vivo effects of recombinant human interleukin-6 in primates: stimulated production of platelets. AB - In cynomolgus monkeys, twice daily subcutaneous injections of recombinant human interleukin-6 (rhIL-6) at doses of 5 to 80 micrograms/kg/d for 14 consecutive days caused dose-dependent increases in platelet count, usually continuing for more than 1 week after cessation of the injections. The count reached a level approximately twofold or more above the preinjection level even at 5 micrograms/kg/d, and at doses of more than 20 micrograms/kg/d, the increase became biphasic with a higher second peak 3 days after cessation of the injections. Morphologic analysis of the bone marrow after the 7 day-injections with 80 micrograms/kg/d revealed a marked increment in size of megakaryocytes compared with control, indicating the promotion of megakaryocyte maturation. Other changes attributable to the rhIL-6 treatment include dose-dependent loss of body weight, anemia, neutrophilia and monocytosis, elevation of serum C-reactive protein and alpha-1 acid glycoprotein levels, and decrease of serum albumin; all of which returned to normal within 1 week after cessation of the injections and were tolerable at doses of less than 10 micrograms/kg/d. These findings suggest that rhIL-6 may be an effective strategy for the treatment of thrombocytopenia. PMID- 2328313 TI - Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: a European survey of the role of marrow purging. AB - We analyzed data from 263 patients with acute myelocytic leukemia (AML) autografted in first remission (CR) during the period from January, 1982 to January, 1987 at one of 34 centers in the European Bone Marrow Transplant Group. The median age of patients was 30 years (range, 1 to 65). The median interval between achieving CR and autografting was 5 months (range, 1 to 23). Of the 263 patients, 131 patients received cytoreductive regimens that included total body irradiation (TBI); the remainder received various combinations of cytotoxic drugs. Sixty-nine patients received autologous marrow purged in vitro with mafosfamide, and 194 received unpurged marrow. The median follow-up was 28 months (range, 12 to 97). For patients with standard risk AML in CR1 autografted after TBI (n = 107), the leukemia-free survival (LFS) was higher, and the probability of relapse was lower in recipients of purged than of unpurged marrow (63% versus 34%, P = .05 and 23% versus 55%, relative risk 0.34, P = .005, respectively). The superior results of purging were most obvious in patients autografted within 6 months of achieving CR (probability of relapse, 20% versus 61%, P = .01). Patients with longer intervals between CR and autografting had higher LFS and lower probability of relapse than those autografted early in CR (intervals greater than 9 months, 7 to 9 months, 4 to 7 months, and less than or equal to 3 months: LFS = 56%, 40%, 35%, 27%, P = .007, probability of relapse = 25%, 56%, 59%, 67%, P = .005; respectively). We conclude that marrow purging with mafosfamide may be valuable for patients autografted early in first CR. PMID- 2328314 TI - Essential thrombocythemia in two sisters originating from different stem cell levels. AB - We report the rare occurrence of essential thrombocythemia (ET) in two sisters. In one patient, the clinical phenotype of the disease evolved from ET to polycythemia vera (PV) after 4 years of follow-up. Clonal hematopoiesis was established in both cases by X-chromosomal inactivation analysis using a DNA polymorphism of the phosphoglycerate-kinase (PGK) gene. Cell separation studies suggested a common ancestor for granulocytes, monocytes, and T lymphocytes in one patient; however, in her sister, monoclonality could only be demonstrated convincingly for the granulocyte fraction. Our data indicate that ET may originate from heterogenous stem cell levels. PMID- 2328315 TI - Phorbol 12-myristate 13-acetate-induced development of functionally active mast cells in W/Wv but not Sl/Sld genetically mast cell-deficient mice. AB - The normal skin and other tissues of adult genetically mast cell-deficient WBB6F1 W/Wv or WCB6F1-Sl/Sld mice contain less than 1.0% the number of mast cells present in the corresponding tissues of the congenic normal (+/+) mice. We previously reported that mature dermal mast cells developed locally in the skin of W/Wv, but not Sl/Sld, mice at sites of chronic idiopathic dermatitis. We now report that the repeated application of phorbol 12-myristate 13-acetate (PMA) to the ear skin of either W/Wv or +/+ mice induces both dermatitis and a striking and dose-dependent increase in the number of dermal mast cells. The number of dermal mast cells at sites treated for 6 weeks with 5 micrograms PMA, three times per week, was 39 +/- 7/mm2 and 305 +/- 34/mm2 for W/Wv and +/+ mice, respectively; the corresponding values for vehicle-treated skin were 1.5 +/- 1.0/mm2 and 145 +/- 8/mm2, respectively. The PMA-induced dermal mast cells in W/Wv mice appeared mature by morphology, stained with the heparin-binding fluorescent dye, berberine sulfate, and were competent to express IgE-dependent passive cutaneous anaphylaxis responses. The development of mast cells was a local, not systemic, effect of PMA treatment. PMA treatment also induced dermatitis in both WCB6F1-Sl/Sld and +/+ mice, but was associated with increased numbers of dermal mast cells only in the WCB6F1(-)+/+ mice. PMA treatment had no detectable effect on the ability of bone marrow-derived cultured mast cells to survive in the skin of Sl/Sld mice. These findings establish a convenient model system for analyzing factors associated with the development of endogenous populations of mast cells in genetically mast cell-deficient W/Wv mice. PMID- 2328316 TI - Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients. AB - The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV-DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti HBs and anti-HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV-DNA may coexist with markers thought to reflect immunity against HBV. PMID- 2328317 TI - Polymerization defect of fibrinogen Baltimore III due to a gamma Asn308----Ile mutation. AB - Fibrinogen Baltimore III, a congenital abnormal fibrinogen with impaired fibrin monomer polymerization, displays a normal gamma-chain and a gamma-variant that has an apparently lower relative molecular weight (mol wt) than normal on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Reverse phase high performance liquid chromatography (HPLC) analysis of the lysyl endopeptidase digest of the purified gamma-chains of fibrinogen Baltimore III revealed the presence of a peptide that is not found in the digest of the normal fibrinogen gamma-chain. Amino acid sequence analysis of this peptide indicated that the gamma-chain residue 308, asparagine, is replaced by isoleucine. Concanavalin A bound both normal and variant gamma-chains of fibrinogen Baltimore III, indicating that the carbohydrate moiety is not altered and is not responsible for the increase in electrophoretic mobility of the Baltimore III gamma-chain. This study suggests that the integrity of gamma Asn308 is critical for fibrin monomer polymerization, since alteration to either a basic (fibrinogen Kyoto I, Asn--- Lys) or hydrophobic (Asn----Ile) residue results in significantly delayed polymerization of fibrinogen to fibrin. PMID- 2328318 TI - Isochromosome 17q in Ph1-negative leukemia: a clinical, cytogenetic, and molecular study. AB - We report on eight patients who were 35 to 77 years old with an isochromosome 17q as the sole structural chromosomal anomaly. Additional numerical chromosomal changes were a trisomy 8 or 17 in two cases each and a trisomy 19 in one case. Five patients had myelodysplastic syndrome (MDS) diagnosed according to the FAB nomenclature as chronic myelomonocytic leukemia (CMML) in two cases, refractory anemia with excess of blasts in transformation (RAEBt) in two cases, and refractory anemia with excess of blasts (RAEB) in one case. One patient suffered from a myeloproliferative disorder (MPS). All cases progressed to acute nonlymphocytic leukemia (ANLL) type M1, M2, or M4 in a period of 2 to 30 months after initial diagnosis, except one patient with RAEBt who died within 2 months. Two patients presented with ANLL-M2 at time of diagnosis. Treatment during the chronic phase of disease consisted of mild cytoreduction and/or substitution of platelets or red blood cells. One patient with CMML received an allogeneic bone marrow graft and relapsed after 33 months with ANLL-M1. Treatment results for overt leukemia were poor, and survival was short, lasting from 1 to 4 months. Overall survival was 1 to 37 months (median duration, 6.5 months). Molecular studies in two cases revealed neither a BCR rearrangement nor a translocation of the ABL protooncogene, as observed in Ph1-positive chronic myeloid leukemia (CML). Thus, an i(17q) anomaly seems to identify a distinct subgroup of mostly myelodysplastic and, less frequently, myeloproliferative disorders that progress rapidly to ANLL, respond poorly to chemotherapy, and are associated with short survival after transformation. PMID- 2328319 TI - Hereditary pyropoikilocytosis and elliptocytosis in a white French family with the spectrin alpha I/74 variant related to a CGT to CAT codon change (Arg to His) at position 22 of the spectrin alpha I domain. AB - We describe a white French family in which 12 subjects presented with hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP). Eight of these subjects were shown to be heterozygous for a spectrin (Sp) alpha I/74 variant, as demonstrated by analysis of partial tryptic digestion fragments of spectrin. This abnormal peptide pattern was associated with a decreased ability of Sp dimers to self-associate. In this kindred, in which four generations were available for study, the clinical expression varied from mild HE to HPP with an intermediate status of hemolytic HE. The severity of the disease appeared to be correlated both with the estimated amount of variant Sp (42% to 65%) and the excess of Sp dimers found in the membrane (30% to 51%, with a normal value of 3.7% +/- 1.6%). Reassociation studies using isolated Sp alpha and beta chains from an affected patient and an unaffected control subject showed that the Sp alpha I/74 Kd abnormal tryptic peptide resulted from a defect in the Sp alpha chain. Partial amino acid sequencing showed that the Sp alpha I/74 Kd peptide resulted from cleavage at lysine residue 42 of the Sp alpha I/80 Kd domain. Knowledge of the exon/intron organization of the human alpha Sp gene allowed us to amplify by the polymerase chain reaction the second exon of the alpha Sp gene in total cellular DNA of the HPP proposita. The amplified fragment was subcloned and sequenced. We found a G to A base substitution in the 22nd codon (CAT for CGT), which changes the normal arginine to a histidine. Hybridization of amplified DNAs with allele specific oligonucleotides corresponding to the normal and mutant sequences confirmed the presence of the mutation in six other HE and HPP members of the family. The identification of this mutation at the DNA level confirmed the transmission of the same molecular defect in Sp through four generations but with different patterns of clinical expression. PMID- 2328320 TI - Mechanical properties of sickle cell membranes. AB - The mechanical properties of sickle erythrocyte membranes were evaluated in the ektacytometer. When ghosts from the total red blood cell population were examined, the rigidity of the resealed ghosts and their rate of fragmentation by shear stress (t1/2) were normal. However, fractionation on Stractan density gradients revealed that sickle cells were heterogenous in their membrane mechanical properties. The ghosts from dense cell fractions exhibited both increased rigidity and decreased stability. Presumably, these altered mechanical properties are a reflection of the well-documented biochemical damage found in irreversibly sickle cell membranes. Nevertheless, neither of the alterations in mechanical properties are likely to be significant elements in the hemolysis of sickle cell anemia. Earlier studies of abnormal erythrocytes suggest that increases in membrane rigidity per se do not increase hemolysis, and they are, therefore, unlikely to do so in this case. The stability of membranes from the dense cell fractions was reduced to about two thirds of the control value. Comparison with the results of studies of red blood cell membranes with genetically defective or deficient spectrin suggests that a reduction in t 1/2 of 50% is not associated with significant increases in the rate of hemolysis. Although altered ghost stability and flexibility can be demonstrated in dense sickle cells, these changes in membrane mechanical properties are not likely to be significant factors in the hemolytic process. PMID- 2328321 TI - Busulfan disposition in children. AB - Children receive busulfan orally as part of myeloablative therapy before bone marrow transplantation for malignant and nonmalignant conditions. Children have been reported to have a low incidence of severe toxicity and significant rates of failure to achieve full engraftment. We evaluated the disposition of busulfan in children between 2 months and 3.6 years of age with lysosomal storage diseases, leukemia, and immunodeficiency disorders receiving oral doses of 1 or 2 mg/kg using a gas chromatographic assay. Peak concentrations were lower than those previously reported for adults, ranging from 1.4 to 5.2 mumol/L. The harmonic mean of the elimination half-life was 92 minutes, which is only slightly faster than that for adults (140 minutes). However, the area under the curve ranged from 400 to 1,000 (715 +/- 240) mumol.min/L, substantially lower than in adults receiving 1 mg/kg (range, 710 to 5,100 mumol.min/L; mean +/- SD, 2,180 +/- 1,200). The apparent volume of distribution (assuming complete bioavailability) ranged from 0.28 to 3.53 L/kg (1.42 +/- 0.86), which is more than twice that reported for adults (0.60 +/- 0.42). Busulfan clearance rate normalized to surface area is twice as high in children (200 +/- 100 mL/min/m2) as it is in adults (95 +/- 54 mL/min/m2). Alterations in bioavailability (absorption or first pass elimination) or in actual volume of distribution may account for these differences in drug disposition. The observed differences suggest the need for separate phase I dose escalation studies in children with accompanying pharmacokinetic assessment. PMID- 2328322 TI - Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases. AB - From April, 1985, to February, 1989, 102 consecutive patients received unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia (CML) at four centers. Median age of the group was 31 years (range, 4.5 to 51 years). Fifty-four patients were in first chronic phase (CP) at time of transplantation, and 48 had evidence of more advanced disease (AD) (accelerated phase, 32; blast crisis, 9; second CP, 7). In 44 cases, the donor and recipient were identical at the HLA A, B, and DR loci and were nonreactive in bidirectional mixed leukocyte culture (MLC) ("matched"). In 58 cases, nonidentity between donor and recipient could be determined at at least one HLA locus or in bidirectional MLC ("mismatched"). Fifty-eight patients were prepared for transplantation with a combination of cyclophosphamide and fractionated total body irradiation (FTBI) and received acute graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate alone or in combination with cyclosporine, prednisone, or antithymocyte globulin (ATG). In 44 cases, patients received preparative agents in addition to cyclophosphamide and FTBI, and marrow depleted of mature T lymphocytes by ex vivo incubation with either anti-CD3 antibody plus complement (n = 24) or Campath-1 (n = 20). Engraftment defined by a peripheral blood neutrophil count greater than 0.5 X 10(9)/L was demonstrated in 92 cases and occurred at a median of 22 days (range, 11 to 46 days). In 10 cases, peripheral blood evidence of engraftment did not occur, and in one case, engraftment was followed by aplasia. Hematologic relapse was seen in four cases. Recurrence or persistence of the Ph1 chromosome without evidence of hematologic relapse occurred in four additional cases. The incidence of grade II to IV acute GVHD is 65% (95% confidence interval [CI], +/- 10%). After adjustment for recipient age and donor matching status, recipients of T lymphocyte-depleted donor marrow had a significantly lower incidence of grade II to IV acute GVHD (P less than .01); however, T depletion was not significantly associated with improved survival (P = .34), disease-free survival (P = .51), or increased incidence of relapse (P = .39). Of 102 patients, 46 are alive, with a median survival of 12 months (range, 3 to 46 months), and the Kaplan-Meier estimate of disease-free survival is 29% (95% CI, +/- 9%) for the entire group at 2 1/2 years.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2328323 TI - Expression of human adenosine deaminase in mice after transplantation of genetically-modified bone marrow. AB - A high titer retroviral vector was used to transfer a human adenosine deaminase (h-ADA) cDNA into murine bone marrow cells in vitro. The h-ADA cDNA was linked to the retroviral promoter, and the vector also contained a neomycin phosphotransferase gene as a selectable marker. Infected marrow was transplanted into syngeneic W/Wv recipients, and h-ADA expression was monitored for 5.5 months. Several weeks after transplantation, h-ADA was detected in the erythrocytes of all nine recipients, eight of which expressed levels equal to the endogenous enzyme. This level of expression persisted in two of six surviving mice, while expression in three others stabilized at lower, but readily detectable, levels. Only one mouse had no detectable h-ADA after 5.5 months. Vector DNA sequences with common integration sites were found in hematopoietic and lymphoid tissues of the mice at 5.5 months, providing evidence that hematopoietic stem cells had been infected. Furthermore, all mice transplanted with marrow that had been selected in G418 before infusion had multiple vector copies per genome. While this category included the two highest h-ADA expressors, it also included the negative mouse. Thus, multiple copies of the vector were not sufficient to guarantee long-term h-ADA expression. Mice were monitored for "helper virus" infections with an assay designed to detect a wide range of replication-competent retroviruses, including those endogenous to the mouse genome. No helper virus was detected in the two highest h-ADA expressors, ruling out helper-assisted vector spread as a cause of the high h-ADA expression. These results help provide a foundation for the development of somatic gene therapy techniques to be used in the treatment of human disease. PMID- 2328324 TI - The never-ending controversies in Hodgkin's disease. PMID- 2328325 TI - Recombinant interferon alfa-2B in refractory idiopathic immune thrombocytopenia. PMID- 2328326 TI - Survival effect of systemic therapy on patients developing metastatic breast carcinoma. AB - A multivariate analysis was performed to assess the effect of post-relapse systemic therapy on a series of patients with metastatic breast cancer who at initial presentation had no detectable metastases (Mo), were less than or equal to 70 years of age, presented with unilateral localized disease and no other associated malignancy, and were treated between 1965 and 1984 with successive protocols for primary disease and subsequently developed distant metastasis. All 760 patients analyzed relapsed with at least one metastasis, and were studied retrospectively with no selection criteria according to any specific protocol. All had recorded clinical data on menopause, stage, clinical tumor aggressiveness (PEV), initial chemo or hormonal therapy, and time to relapse, and had ongoing follow up at our Center, with salvage chemotherapy and/or hormonal therapy having been given to some but not all patients. A brief metastasis-free survival (p less than 0.000001), and factors associated with electing pre-relapse chemotherapy (p less than 0.000001) were associated with shortened post-relapse survival, while post-relapse therapy (chemo p less than 0.0001, and hormonal p less than 0.00001, replacing chemotherapy in the model) apparently increased post-relapse survival in the group overall. This result was similar in the inoperable patient group [with inflammatory breast carcinoma an additional risk factor (p less than 0.0005)], as well as the operable group. However, in the operable group, when the pathologic criteria of histologic grade and nodal status were introduced into the analysis, post-relapse therapy was not seen to be an important factor for survival in any subgroup.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328327 TI - Immunohistochemical staining of bone marrow biopsies for detection of occult metastasis in breast cancer. AB - Immunohistochemical (IHC) techniques should allow for a greater detection of bone marrow micrometastasis in patients with breast carcinoma. We studied a series of bone marrow (BM) biopsies negative by conventional histologic techniques from 93 patients with breast carcinoma. Prior to this study, twelve BM biopsies, positive by conventional histology, were stained with a panel of monoclonal antibodies (MoAb), directed either against cytokeratin (KL1, AE1-AE3, CAM5-2) or epithelial membrane antigen (EMA, HMFG2). KL1 appeared to be the most sensitive of the markers used in the detection of metastases and is available commercially. It therefore was the only MoAb used with the series of 93 BM biopsies negative by conventional examination. Within this series, among 45 patients clinically suspected of having bone marrow metastasis but with BM biopsies negative by conventional staining, one case showing myelofibrosis stained positive with KL1 demonstrating isolated tumor cells. For the 48 patients without suspicion of bone marrow metastasis at initial diagnosis for breast carcinoma, KL1 revealed no marrow metastasis. Single bone marrow biopsy techniques whether stained by conventional or IHC methods do not appear to be useful tests to detect occult bone marrow metastasis, especially at initial diagnosis of clinically Mo breast carcinoma patients. PMID- 2328329 TI - Mammography and hereditary breast cancer. PMID- 2328330 TI - A case of bilateral bloody discharge from the breast. PMID- 2328328 TI - Season of tumour detection influences factors predicting survival of patients with breast cancer. AB - The rate of initial detection of breast tumours varies during the year in a seasonal fashion, more tumours being discovered in late spring/early summer than at other times of the year. This phenomenon is particularly pronounced in young women (less than 50 years) with progesterone receptor positive tumours. The present study investigates whether season of tumour detection influences the predictive capacity of several recognised prognostic and risk factors in patients with breast cancer. Axillary nodal status, tumour progesterone receptor status, and season of tumour detection significantly influenced survival in both older (greater than 50 yrs) and younger (less than 50 yrs) patients. Parity, lactational history, body mass index, tumour oestrogen receptor status, and patient age also influenced survival, but these effects were significant only in age groups less than 50 or greater than 50 yrs. Season of detection of tumour did not effect the prognostic significance of axillary nodal status. However, the effect of oestrogen receptor status on survival was more significant in patients who detected their tumours in the spring/summer compared with winter (odds ratio 0.52 and 0.73 respectively). Negative progesterone receptor status was associated with significant poorer survival only in patients with tumours found in the winter. There was a significant survival disadvantage for nulliparous compared with parous women with breast cancer who were greater than or equal to 50 years at diagnosis, and for women who had never lactated compared with those who had lactated, but this disadvantage was restricted to those who found their tumours in the summer. An increased body mass index (greater than or equal to 28) was associated with decreased survival, but this was significant only for those detecting tumours in winter. The increased incidence of detection of breast cancer in spring/summer may reflect cyclic influences on tumour growth. Such influences may be hormonal in nature and may underlie the effect of season of tumour detection on the prognostic influence of lactation, parity, body mass index, and oestrogen and progesterone receptor status in patients with breast cancer. PMID- 2328331 TI - Depression in homicidal adolescents. AB - The problem of adolescents who commit homicides is of increasing concern in its own right, as well as from the possibility of their facing execution. In this study, a psychiatric and psychological assessment was aimed at screening out a group of juveniles who were being considered for certification to adult court in terms of depressive symptomatology. Within a group of 213, 30 males and 14 females were assessed as depressed by clinical history, the Minnesota Multiphasic Personality Inventories (MMPI) and the Beck Depressive Inventory (BDI). Empirical and psychosocial data attempted to differentiate significant developmental components related to the homicides, as well as differences between the 30 males and 14 females. Although the problem of predicting such behavior from descriptive characteristics remains elusive, certain patterns were present among diverse homicidal behaviors. In conclusion, some psychodynamic hypotheses are offered. PMID- 2328332 TI - Threats and assaults against psychiatrists. AB - In this article, the authors review the literature on surveys pertaining to threats and assaults on psychiatrists and report the results of a questionnaire sent to Oregon psychiatrists. Although the responding psychiatrists were experienced clinicians, they appear to have had relatively little life experience with aggression. Assaults and threats were frequent in their careers, occurred across a variety of clinical settings, and involved a wide range of patients. The authors discuss specific strategies for psychiatrists to minimize the effects of patient threats and assaults and suggest ways in which organized psychiatry can help with the danger and sequelae of patient violence. PMID- 2328333 TI - DSM-III diagnoses and offenses in committed female juvenile delinquents. AB - The relationship between juvenile delinquency and psychiatric disorders remains poorly understood. However, it is becoming more apparent that the spectrum of psychiatric illness present in juvenile delinquents is broader than once believed. Fifteen female juvenile delinquents committed to a residential treatment program were assessed for DSM-III diagnoses, using a structured diagnostic interview, the Diagnostic Interview for Children and Adolescents (DICA). A search of the literature revealed no other reports using the DICA in female juvenile delinquents. A broad spectrum of current and past diagnoses was discovered, including conduct disorder (100%), substance abuse/dependence (87%), major depression (67%), and anxiety disorders (47%). The average number of lifetime diagnoses per subject was 4.7; current diagnoses averaged 3.4 per subject. Additionally, criminal and status offense records were obtained for each subject. No significant relationship was noted between diagnoses and categories of offense. These results add further evidence for the presence of frequent and severe psychiatric disturbances in this population, and the need for increased clinical and research efforts by the psychiatric community. PMID- 2328334 TI - The fusion of medicine and law for in extremis health and medical decisions: does it produce energy and light or just cosmic debris? PMID- 2328335 TI - Civil commitment: a range of patient attitudes. AB - The authors interviewed adult civil commitment excandidates about their perceptions of commitment six months after discharge. Scales were developed for the following constructs: perceived need of commitment, perceived personal consequences of commitment, view of medication, view of primary hospital physician, and view of hospital experience. Excandidates had a mixed view of commitment. The majority reported positive views, but a substantial minority endorsed negative descriptors. PMID- 2328336 TI - Women who molest children. AB - In only nine of approximately 600 cases of child molestation in New Hampshire and Vermont was the perpetrator found to be a woman. Case histories and some testing data show a history of sexual assault as a child, frequent offense in the company of a dominant male partner, and a major disinhibition as a result of severe character disorder or limited intelligence. These factors not only interfered with maternal bonding and nurturing behavior but also contributed to suspension of judgment about the appropriateness of sexual contact with children. PMID- 2328337 TI - A study of families in high-conflict custody disputes: effects of psychiatric evaluation. AB - Each year approximately 2.5 million people divorce, subjecting more than 1 million children to the losses of familial breakup. Hostility in families can be greatly exacerbated by parents' repeated failures to negotiate an altered lifestyle for the family which provides for the children's best interests. Interventions with highly conflictual parents and their children must necessarily address the interface between the mental health and legal professions. How families experience this process must be carefully studied in order to create new strategies for change, not only within the families, but also to facilitate the legal system's cooperation with mental health professionals. To date, little research has been conducted which assesses the efficacy of methods used by mental health professionals to intervene in contested child custody cases. This paper describes a program at the Isaac Ray Center, Inc., designed to help parents settle their custody disputes out of court. The article presents findings based on an 18-month follow-up questionnaire and court records for 45 parents. Data concerning custody settlement, relitigation, and parents' satisfaction with the evaluation process, their attorneys, and the custody outcome are presented and discussed. PMID- 2328338 TI - American forensic psychiatrists who work in state institutions. AB - The authors surveyed a sample of American forensic psychiatrists who work in state institutions. As a group, their respondents tended to be middle-aged, white men, who had little formal training in forensic psychiatry, felt somewhat alienated from their peers, yet who were Board certified in general psychiatry. They tended to be involved primarily in the direct treatment of patients, and most often expressed concerns about the care-and prominent lack of aftercare- received by forensic patients. They also perceived a sense of patient futility in the institutional forensic setting. The authors conclude by recommending that AAPL take a more active role in appealing to and representing such forensic psychiatrists. PMID- 2328339 TI - Monitoring of aflatoxins and ochratoxin A in Czechoslovak human sera by immunoassay. PMID- 2328340 TI - Use of hair as an indicator of environmental lead pollution in women of child bearing age in Karachi, Pakistan and Bangladesh. PMID- 2328341 TI - In vitro methylation and demethylation of mercury compounds by the intestinal contents. PMID- 2328342 TI - Responses of the hepatopancreatic 'B' cells of a terrestrial isopod, Oniscus asellus, to metals accumulated from a contaminated habitat: a morphometric analysis. PMID- 2328343 TI - Profile of hemoproteins and heme-metabolizing enzymes in rats treated with surfactants. PMID- 2328344 TI - Comparative study of the tissue distribution of NADH and NADPH-dependent chloral hydrate reducing enzymes in the rat. PMID- 2328345 TI - Effect of solvents on the photodegradation rates of octachlorodibenzo-p-dioxin. PMID- 2328346 TI - Convenient chemical method for measuring mean temperature at sites of degradation studies in the field. PMID- 2328347 TI - Contamination of rural ponds with pesticide, 1971-85, Ontario, Canada. PMID- 2328348 TI - Survey of farm wells for pesticides, Ontario, Canada, 1986 and 1987. PMID- 2328349 TI - Importance of bioassay volume in toxicity tests using algae and aquatic invertebrates. PMID- 2328350 TI - Physiological responses of juvenile white mullet, Mugil curema, exposed to benzene. PMID- 2328351 TI - Sublethal effects of malathion on channel catfish, Ictalurus punctatus. PMID- 2328352 TI - Effect of endosulfan on acid and alkaline phosphatase activity in liver, kidney, and muscles of Channa gachua. PMID- 2328353 TI - In vitro cytotoxicities of inorganic lead and di- and trialkyl lead compounds to fish cells. PMID- 2328354 TI - Levels of heavy metals and organochlorine pesticides of cyprinid fish reared four years in a wastewater treatment pond. PMID- 2328355 TI - Uptake of lead, chromium, cadmium and cobalt by Cladophora glomerata. PMID- 2328356 TI - Toxicity and accumulation of chromium in Ceratophyllum demersum L. PMID- 2328357 TI - Heavy metal concentrations in the banana prawn, Penaeus merguiensis, and leader prawn, P. monodon, in the Townsville region of Australia. PMID- 2328358 TI - Metabolites of three structural isomers of butylbenzene in the bile of rainbow trout. PMID- 2328359 TI - Protein engineering: approaches to the manipulation of protein folding. PMID- 2328360 TI - The effect of DOCLINE on interlibrary loan volume and patterns among health sciences libraries in Michigan: preliminary analysis. AB - Six years of statistics on interlibrary lending and borrowing among basic unit health sciences libraries in Michigan are examined to determine the effect of the availability of an automated interlibrary loan system, DOCLINE, on interlibrary lending volume and patterns within Michigan. A trend analysis projection of expected volume is made and the predicted value compared with the actual value following the adoption of the DOCLINE system. Interlibrary loan (ILL) volume is tested to see if yearly volume increases are statistically significant. The number of libraries changing from net lender to net borrower or the reverse after the adoption of DOCLINE is tracked. Results fail to support the expectation that DOCLINE would produce major change in ILL volume or pattern. PMID- 2328361 TI - Criteria-based evaluation of group 3 level memory telefacsimile equipment for interlibrary loan. AB - The Interlibrary Loan, Document Delivery, and Union List Task Force of the Health Sciences Libraries Consortium (HSLC)--with nineteen libraries located in Philadelphia, Pittsburgh, and Hershey, Pennsylvania, and Delaware--accepted the charge of evaluating and recommending for purchase telefacsimile hardware to further interlibrary loan among HSLC members. To allow a thorough and scientific evaluation of group 3 level telefacsimile equipment, the task force identified ninety-six hardware features, which were grouped into nine broad criteria. These features formed the basis of a weighted analysis that identified three final candidates, with one model recommended to the HSLC board. This article details each of the criteria and discusses features in terms of library applications. The evaluation grid developed in the weighted analysis process should aid librarians charged with the selection of level 3 telefacsimile equipment. PMID- 2328362 TI - Impact of changing health care economics on Michigan hospital libraries: report of a survey. AB - In an attempt to determine how efforts to contain the soaring cost of U.S. health care in the 1980s have affected the size and stature of Michigan hospital libraries, a survey was sent out in April 1988 to 156 hospitals across the state. Fifteen of the 97 responding institutions did not maintain libraries during the survey period and were subsequently excluded from the study. Total FTEs in the 82 responding libraries decreased by 6.1%. In the 69 libraries reporting budget data, materials budgets increased, but by less than 7% a year. Eighteen of the 82 libraries had positions reclassified, with 12 (14.6%) assigned downgrades. The trend toward reduced size and perceived value of hospital libraries that emerged from the survey points to the need for regular collection of comprehensive hospital library statistics to assist hospital librarians in effective direction of their profession's course. PMID- 2328363 TI - Productivity measurement in hospital libraries: a case report. AB - This paper examines the concept of productivity measurement and its application in a hospital library. Component steps in development of a typical productivity measurement system are described, including a process for calculation of quantitative workload standards. Problems and potential benefits of participating in productivity measurement programs are discussed, and managerial strategies suggested. PMID- 2328364 TI - The evolving role of the health sciences library in continuing education. Introduction. PMID- 2328365 TI - Continuing education/beyond higher education. AB - Publicly funded institutions, such as NIH, NLM, and state-supported universities, have explicit public service missions that extend beyond the walls of a single institution. During the past few years, national organizations, such as NLM and AAMC, have funded studies and projects to measure how well universities are adapting to technological change and educational reform. The IAIMS models are evidence of universities fostering cooperative rather than duplicative effort. Opportunities and problems facing universities extending systems and services to the private practice setting, to community-based health care HMO's, and to state and local health care agencies are discussed in terms of political, economic, and geographic realities. Instilling lifelong learning concepts begins before the health professional enters practice and is dependent on the emphasis universities place on "excellence in teaching." Without cooperation among core facilities, such as libraries, computer centers, and excellent instructors, continuing education will remain a parochial issue instead of a national thrust toward the continuum of the learning process. If continuing education is to become a high priority for universities and take its place on the education spectrum, flexible policies must be established to accommodate individual practitioners' expectations and interests. PMID- 2328366 TI - The changing paradigm for continuing medical education: impact of information on the teachable moment. AB - The teachable moment is the time when a learner is ready to accept new information for use conceptually or in practice. Adult educators are always searching for that "moment" and models in which it has been incorporated. This article reviews the changing paradigm for continuing education of the health professional and the impact of information from the context of university-based providers of continuing education and information. Providers of continuing education and information face similar external opportunities and threats. The continuing education provider is a "marginal dweller" in the organization. The information provider (the library), although moving in that direction as technology affects the way information is accessed and managed, is much more a part of the core institutional mission. These parallel conditions provide opportunities for both organizations to work closely together to identify successful models to serve the "teachable moments" of all health care practitioners. A range of new library roles that suggest strong interaction with continuing educators is presented. Workable models are identified as well as characteristics of successful models. Suggestions for survival for continuing educators and librarians in "stalking the teachable moment" are discussed. PMID- 2328367 TI - The changing continuing education role of health sciences libraries. AB - Libraries have always organizationally supported the continuing education (CE) objectives of their respective institutions. As CE experts increase their understanding of the learning process and the factors that make CE opportunities successful, it is important that health sciences librarians use this knowledge to enhance their positions as key players in the CE field. This paper surveys the literature related to the roles of health sciences libraries in CE, reports an informal survey of health sciences librarians, and identifies innovative services that integrate the library with the lifelong learning processes of its users. Four distinct support areas are identified in which the library relates to CE (resources, content, education, and information management), illustrating traditional library CE roles and suggesting new opportunities. To be successful in improving the library's role in CE, librarians must attend to their own lifelong learning needs, increase collaboration with educators and CE providers, participate in research that addresses the learning and information assimilation processes, and actively involve the library in the quality filtering process. PMID- 2328369 TI - Experience. PMID- 2328368 TI - Continuing education through videotapes. PMID- 2328370 TI - Clinical medical librarianship. PMID- 2328371 TI - Advocacy of hospital information services: the promise of the 1990s. PMID- 2328372 TI - Resurfacing of skin defects of the hand using the arterialised venous flap. AB - In 22 patients an arterialised venous flap, with arterial blood only flowing through the vein of the flap, was used to cover skin defects of the hand. There were 17 complete successes, four partial successes and one complete failure. The main indications for use of the arterialised venous flap are to cover extensive skin loss with exposed bone or tendon where conventional flaps cannot be applied and to reconstruct the digital arterial defect where both revascularisation and skin coverage are needed. PMID- 2328373 TI - The distally-based radial forearm free flap with valvulotomy of the cephalic vein; a preliminary report. AB - The radial forearm free flap is widely used in microsurgical reconstruction where a thin, hairless flap is required. While the radial artery may be based either proximally or distally, the venous drainage is generally proximally based in order to provide normal flow through the valves. We have utilised this flap in two patients, based distally on both the radial artery and cephalic vein by removing the valves of the cephalic vein. This technique has been employed widely in peripheral vascular surgery of the lower limb and is called the "in-situ" technique. We have found it to be efficacious in taking a proximal skin paddle, which decreases donor site morbidity and allows for a long vascular pedicle. This paper reports on these two patients and describes the technique of valvulotomy of the cephalic vein. PMID- 2328374 TI - The multiple Y-V plasty in linear burn scar contracture release. AB - The technique of the multiple Y-V plasty is described. The records of all 129 patients who underwent surgery to release burn scar contractures over a 5-year period are reviewed. Halfway through this study period the multiple Y-V plasty was introduced, resulting in a marked reduction in the number of Z-plasty and skin grafting procedures carried out. There was an associated fall in the number of wound complications seen and the length of hospital stay required. PMID- 2328375 TI - Immediate placement of tissue expanders in the management of large excisional defects on the face. AB - Where excision of a facial lesion leaves a defect too large for local flap reconstruction, tissue expansion is frequently a more desirable option than a skin graft, providing as it does tissue which exactly matches that which has been lost. For malignant skin lesions where removal should not be delayed by preliminary expansion of the flap, the expander can be placed simultaneously with tumour excision thus keeping the reconstruction to two stages. A temporary skin graft is employed in the interim. Our experience with this approach in five patients with large facial malignancies is presented and discussed. PMID- 2328376 TI - Vulval reconstruction after cancer excision: the island groin flap technique. AB - Many current techniques for vulval reconstruction following cancer excision satisfy the basic requirements for restoration of urinary and sexual function but leave considerable scars on the thigh. We suggest the use of bilateral island groin flaps, which allow a good cosmetic and functional reconstruction with a minimal donor defect and more acceptable scars. This technique also allows good access to the inguinal, crural and iliac lymph nodes through the same incisions, avoiding other scars. PMID- 2328377 TI - The lateral thoracic region flap. AB - The lateral thoracic region flap is based at the level of the 3rd rib on multiple direct cutaneous perforators. It has an excellent vascularity with a dependable length/width ratio of 3:1. The donor area, which lies in a concealed region, can often be closed primarily. The flap is hairless and can be used anteriorly to cover raw areas over breast and axilla and posteriorly over scapula and chest wall. As a distant flap it can be used to resurface raw areas on the ipsilateral upper arm and forearm and contralateral hand. The successful use of the flap in 40 cases in this series confirms its reliability, versatility and convenience. PMID- 2328378 TI - The repair of large peripheral nerves using skeletal muscle autografts: a comparison with cable grafts in the sheep femoral nerve. AB - Recovery of morphological characteristics was compared in the femoral nerves of sheep at varying times up to 10 months after nerve repair. Groups of sheep receiving coaxially aligned freeze-thawed skeletal muscle autografts were compared with those receiving three-strand cable grafts made from autogenous cutaneous nerve. At all times after implantation more nerve fibres could be counted distal to the muscle grafts than distal to cable grafts. Indices of nerve fibre maturation were indistinguishable between the two groups at 10 months. The results are discussed in relation to the possible use of the technique for repairing large mixed nerves. PMID- 2328379 TI - The effect of intense arterial constriction on the survival length of an island flap; an experiment using abdominal flaps in rats. AB - Using rats' abdominal skin flaps, the effects of markedly decreased arterial inflow was investigated. An intense constriction was created with laminated silastic tubes. Survival length of the island flap was reduced by this manipulation and the differences with the control were statistically significant. It was ascertained experimentally that the flap went into necrosis distally and progressed proximally as the arterial inflow decreased. The possible risks of the sleeve technique are also briefly described. PMID- 2328380 TI - Inhibition of human fibroblast growth in vitro by a snake oil. AB - The inhibitory effects of boa constrictor fat (BCF) oil on the growth kinetics of keloid and normal dermal fibroblasts were tested in fibroblasts cultures. BCF significantly (p less than 0.0001) inhibited the in vitro growth of both keloid and normal dermal fibroblasts. Although the active ingredient(s) in this snake oil is not yet determined, it is postulated that fatty acids which are the main constituents of the oil may in part account for this observed in vitro effect. PMID- 2328381 TI - The role of pharyngoplasty in congenital neurogenic speech disorders. AB - Children with dysarthria are often seriously handicapped by their inability to communicate. Velopharyngeal incompetence may contribute to their speech difficulties but the indications for pharyngoplasty are poorly defined. The speech of 41 children, thought to have a defect of neurological origin and referred for possible pharyngoplasty, was assessed by a speech therapist, by nasopharyngoscopy and by multiview videofluoroscopy. These investigations revealed that 16 had velopharyngeal incompetence, with a neurological aetiology, and might be expected to benefit from pharyngoplasty. Independent assessment of the intelligibility of these 16 children before and after pharyngoplasty has been related to their preoperative oropharyngeal function. The majority benefited from surgery, some substantially. In particular, good lip and tongue function are shown to be necessary to achieve improved intelligibility. The roles of age, intelligence and aetiology in the success of pharyngoplasty are discussed. PMID- 2328382 TI - Neonatal cleft lip repair in Ayrshire; a contribution to the debate. AB - Neonatal cleft lip repair has been the normal practice in Ayrshire, Scotland, for the last 10 years. The surgical results are briefly presented. Anaesthetic and paediatric considerations are discussed. Assuming careful preoperative assessment is made, the procedure carries minimal morbidity, can give good results and is believed to offer distinct advantages to the parents and child. PMID- 2328383 TI - Use of methyl methacrylate in bone reconstruction. AB - We have used methyl methacrylate as bone substitute in 8 clinical cases for a variety of problems, from simple nasal implants to more complicated mandibular reconstruction including the temporomandibular joint complex. The follow-up period, which ranged up to 36 months, has been very encouraging and we continue to use this material routinely in our Unit. We present our experience. Three illustrative cases are described. PMID- 2328384 TI - Congenital earlobe cleft: a new technique for repair. AB - A new procedure utilising a local hinge flap to reconstruct the congenital cleft earlobe deformity is described. Its technique and advantages are outlined. PMID- 2328386 TI - The deep inferior epigastric artery local musculocutaneous flap: a method of preserving sensation. AB - We present a case in which an island extended inferior epigastric artery musculocutaneous flap, used to resurface an amputation stump, retained sensation. The reasons for this are discussed. PMID- 2328385 TI - Facial dysmorphology in the neglected paediatric head and neck burn. AB - The morphological distortion of the facial skeleton induced by untreated paediatric burns of the head and neck reinforces the theories of craniofacial growth and the modern principles of acute burn management and post-burn facial reconstruction. PMID- 2328387 TI - A new surgical approach to exomphalos. AB - This report describes the use of tissue expansion for late reconstruction of giant exomphalos. An unexpected advantage was reconstruction of the anterior rectus sheath using the posterior capsule formed by the tissue expanders. PMID- 2328388 TI - Transfer of the third, fourth and fifth toes for one-stage reconstruction of the thumb and two fingers. AB - This paper describes a reconstruction of both hands after amputations because of severe frostbite. The right hand was reconstructed in two stages by free second toe and double toe transfer. A one-stage free transfer of the third, fourth and fifth toes was used for reconstruction of the left hand. PMID- 2328389 TI - The preparation of divided nerve ends. AB - Divided peripheral nerves often require trimming due to the "mushrooming" of the fascicles. However, in practice, it can be very difficult to perform atraumatically as the nerve tends to behave like "soggy spaghetti". A technique is described which helps to stabilise the cut end of the fascicles, thus allowing satisfactory trimming. This involves the use of fibrin glue. PMID- 2328390 TI - Microsurgical practice on avulsed skin. AB - The use of avulsed skin is recommended as a source of vessels for trainees to practise microvascular techniques. If it cannot be used immediately it can be stored in the refrigerator for later use. PMID- 2328391 TI - Characterization of presynaptic vascular muscarinic receptors inhibiting endogenous noradrenaline overflow in the portal vein of the freely moving rat. AB - 1. In the portal vein of permanently cannulated, freely moving, unanaesthetized rats, methacholine (MCh) is able to inhibit the electrically-evoked endogenous noradrenaline (NA) overflow. This inhibition is mediated by presynaptic inhibitory muscarinic heteroreceptors. 2. By use of pirenzepine, 4 diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) and AF-DX 116 as M1-, M3 , and M2-selective antagonists respectively, the MCh (0.1 microM)-induced inhibition of the electrically-evoked NA overflow could be reversed to the control stimulation value dose-dependently. 3. The potency order of the antagonists was: 4-DAMP greater than AF-DX 116 greater than pirenzepine, pIC50 values being 8.50, 7.96 and 7.01, respectively. 4. From these results it was concluded that the inhibitory presynaptic heteroreceptors in the portal vein of conscious unrestrained rats are of the cardiac M2-subtype. PMID- 2328392 TI - Vasopressin and stress-induced antinociception in the mouse. AB - 1. Arginine vasopressin produced antinociception in the hot-plate test after intracerebroventricular injection (0.5 micrograms) and in the acetic acid abdominal constriction test after intraperitoneal injection (0.1 mg kg-1). 2. The antinociception produced by arginine vasopressin was sensitive to deamino(CH2)5Tyr(Me) arginine vasopressin (0.5 micrograms i.c.v.; 0.1 mg kg-1 i.p.) but not to naloxone (5 micrograms i.c.v.; 2 mg kg-1 i.p.) 3. Arginine vasopressin when administered by the intracerebroventricular route, but not by the intraperitoneal route, produced characteristic behaviour which was sensitive to deamino(CH2)5Tyr(Me) arginine vasopressin (0.5 micrograms, i.c.v.). 4. A 3 min swim at 20 degrees C produced antinociception on the hot-plate which was sensitive to naloxone (0.4 mg kg-1, i.p.) but not to deamino(CH2)5Tyr(Me) arginine vasopressin (0.5 micrograms, i.c.v.). 5. The reduction in the number of acetic acid-induced abdominal constrictions produced by a 30 s swim at 30 degrees C was not sensitive to either naloxone (2 mg kg-1, i.p.) or deamino(CH2)5Tyr(Me) arginine vasopressin (0.1 mg kg-1, i.p.). 6. Arginine vasopressin, at high doses, is antinociceptive in the mouse but does not appear to mediate stress-induced antinociception in this species. PMID- 2328393 TI - Caffeine acting on pregnant rat myometrium: analysis of its relaxant action and its failure to release Ca2+ from intracellular stores. AB - 1. The effect of caffeine on mechanical activity was studied in pregnant rat myometrium. 2. In muscle cells with intact plasmalemmae, caffeine (0.1-50 mM) produced no contraction whatever the experimental conditions. 3. Caffeine (0.1-10 mM) inhibited, in a concentration-dependent manner, contractions induced by electrical stimulation, potassium-rich (60 mM K+) solution, sodium-free solution or oxytocin (22.5 nM). 4. In Ca2(+)-free solution, various substances (oxytocin, sodium orthovanadate and prostaglandin E2) evoked sustained contractions that were suppressed by caffeine (5-10 mM). When caffeine (greater than 5 mM) was applied during Ca2(+)-loading of the tissue (2.1 mM Ca2+, 5 min) in the presence of a K(+)-rich solution, the subsequent transient contraction induced by a short application (10s) of oxytocin (22.5 nM) in Ca-free solution was reduced (63 +/- 3.5% reduction for 20 mM caffeine, n = 4). 5. In saponin-skinned strips, application of caffeine (5-10 mM) during loading of the Ca2(+)-store increased the subsequent contraction induced by myo-inositol 1,4,5 trisphosphate (IP3, 10 microM). Caffeine (10-30 mM) decreased calcium-activated contractions in skinned fibres lacking a functional internal Ca-store. This effect was reduced by the cyclic AMP-dependent protein kinase inhibitor Thr-Thr-Tyr-Ala-Asp-Phe-Ile-Ala-Ser Gly-Arg-Thr-Gly-Arg-Arg-Asn-Ala-Ile- His-Asp (8 microM). 6. In conclusion, it is suggested that the inability of caffeine to cause spasm of rat myometrium is due to the absence of a caffeine-sensitive calcium-release channel in the sarcoplasmic reticulum. Relaxant effects of caffeine can be explained by mechanisms leading to a decrease in both the cytoplasmic free Ca2+ concentration and the Ca2 +-sensitivity of the contractile machinery. PMID- 2328394 TI - Eosinophil accumulation in pulmonary airways of guinea-pigs induced by exposure to an aerosol of platelet-activating factor: effect of anti-asthma drugs. AB - 1. Exposure of guinea-pigs to aerosols of platelet activating factor (PAF) (0.01 to 100 micrograms ml-1) induced a dose-dependent increased incidence of eosinophils in bronchoalveolar lavage fluid (BAL) at 48 h. Total leucocyte numbers and the percentages of lymphocytes and neutrophils were unchanged in BAL fluid. 2. Increased numbers of eosinophils were detected in BAL 1 h after exposure to PAF but eosinophilia was not maximal until 48 h. One week after exposure to PAF, the percentage of eosinophils in BAL was within the normal range. 3. Depletion of circulating platelets or neutrophils by intravenous injection of specific antisera did not modify accumulation of eosinophils in the airway lumen following inhalation of PAF (10 micrograms ml-1). 4. PAF-induced pulmonary airway eosinophil accumulation was inhibited by treatment with SDZ 64 412, a selective PAF-antagonist, whether the compound was administered before, or 30 min after, inhalation of PAF. 5. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was inhibited by prior treatment with aminophylline, cromoglycate, ketotifen, dexamethasone and AH 21-132. 6. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was not inhibited by prior treatment with indomethacin, salbutamol or mepyramine. PMID- 2328395 TI - Locomotor activity in rats after administration of nicotinic agonists intracerebrally. AB - 1. Nicotine (0.13 and 0.4 mg kg-1, s.c.) increased the ambulatory component of locomotor activity in rats previously exposed to the drug. Nicotine did not increase repeated movements reliably. 2. An infusion of either nicotine (8 micrograms) or the potent nicotinic agonist cytisine (4 micrograms) into the ventral tegmental area of the forebrain increased ambulation but not repeated movements. 3. An infusion of nicotine or cytisine into the nucleus accumbens, striatum, dorsal hippocampal formation or motor thalamus did not increase ambulatory or repeated movements. 4. Mecamylamine (0.1-1.0 mg kg-1, s.c.) blocked increases in locomotor activity produced by an infusion of nicotine or cytisine into the ventral tegmental area. 5. The locomotor activity produced by systemically administered nicotine may be mediated, in part, through nicotinic receptors located in the ventral tegmental area of the mesolimbic dopamine system. PMID- 2328396 TI - Effect of ethanol on eicosanoid synthesis by human gastric and colonic mucosal pieces. AB - 1. Human gastric and colonic mucosa obtained at operation was cut into small pieces and incubated with different concentrations of ethanol. 2. Ethanol (5-40%) caused a concentration-dependent increase in the amounts of prostaglandin E (PGE), thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and (up to 20% ethanol) leukotriene C4/D4 (LTC4/D4) in incubates of mucosal pieces from either region. 3. Higher concentrations of ethanol usually caused small increases or reductions of eicosanoid levels; gastric mucosal PGE and 6 keto-PGF1 alpha were still increased by 100% ethanol, whereas TXB2 was unaltered, and LTC4/D4 was reduced. With the colonic mucosa, 100% ethanol increased PGE but reduced the other eicosanoids. 4. Gastric mucosal pieces incubated in water or phosphate buffer yielded generally similar amounts of eicosanoids. However, colonic mucosa yielded more when incubated in water, possibly indicating a greater sensitivity to osmotic damage. This difference between the two regions is consistent with the ability of the gastric mucosa to resist damage by water on its epithelial surface. PMID- 2328397 TI - Resiniferatoxin, a potent capsaicin-like stimulator of peripheral nociceptors in the neonatal rat tail in vitro. AB - 1. A spinal ventral root response was measured following the activation of peripheral fibres by noxious (heat at 48 degrees C, capsaicin, bradykinin) and innocuous (brush) stimuli in a preparation of the neonatal rat spinal cord-tail maintained in vitro. 2. Following superfusion of the tail with 0.1-1.0 nM of the potent irritant, resiniferatoxin (RTX), brief, irregular depolarization and a selective loss of capsaicin sensitivity was produced. RTX 10-100 nM evoked a tonic response, initiated transient irregular depolarizations and densitization to further applications of RTX and capsaicin but not to other stimuli. Following RTX 1 microM a prolonged loss of sensitivity to all noxious stimuli was produced. 3. When a selective densitization to capsaicin was produced by a long application of capsaicin, RTX was also ineffective. 4. Superfusion of the tail with 4 beta phorbol, 12, 13-dibutyrate (PDBu), a protein kinase C activator, stimulated capsaicin-sensitive peripheral fibres. Prolonged administration of PDBu attenuated or abolished further responses to PDBu and bradykinin but responses to RTX and capsaicin were unchanged. The protein kinase C inhibitor staurosporine (50-200 nM), attenuated the effects of PDBu and bradykinin but not those of RTX or capsaicin. 5. The present data suggest that neither RTX nor capsaicin act on peripheral nociceptors via a phorbol ester-like stimulation of protein kinase C. Rather, RTX acts on nociceptors by a similar mechanism to capsaicin. These effects may be the basis for the irritant properties of RTX and may further relate to the antinociceptive actions observed in vivo. RTX is therefore a potent new tool with which to investigate the properties of nociceptive neurones and provides a prototype for further development of antinociceptive agents. PMID- 2328398 TI - Effect of neuropeptide Y on cardiac output, its distribution, regional blood flow and organ vascular resistances in the pithed rat. AB - 1. The effects of neuropeptide Y on cardiac output, its distribution and organ vascular resistances were determined with tracer microspheres in pithed rats. 2. Neuropeptide Y increased blood pressure by increasing both cardiac output and total peripheral resistance. The increase in cardiac output was due to an increase in stroke volume as heart rate was not changed. Increased vascular resistance in the splenic, renal, testicular, epididymal, skeletal muscle, large intestinal and mesenteric vascular beds contributed to the increase in total peripheral resistance. Vasoconstriction was most pronounced in the mesenteric bed. 3. This study indicates that neuropeptide Y increases blood pressure by increasing cardiac output and total peripheral resistance. The increased cardiac output is possibly due to an increase in venous return, whilst the increased total peripheral resistance was due to regional vasoconstriction, particularly in the mesenteric bed. PMID- 2328399 TI - Anti-inflammatory activity of bee venom peptide 401 (mast cell degranulating peptide) and compound 48/80 results from mast cell degranulation in vivo. AB - 1. The relationship between the anti-inflammatory activity of the bee venom peptide 401 in the carrageenin-induced oedema of the rat hind paw and its mast cell degranulating activity has been reinvestigated. 2. Mast cell degranulation caused by compound 48/80 (10 mg kg-1) or by allergen challenge in rats sensitized to Nippostrongylus brasiliensis also suppressed rat hind paw oedema in the same test. 3. The anti-inflammatory activities of peptide 401 and compound 48/80 were partially suppressed by pretreatment of rats with mepyramine and methysergide, at doses (2.5 mg kg-1) that completely suppressed skin reactions to these mast cell derived amines. Pretreatment of rats with compound 48/80 also suppressed the apparent anti-inflammatory actions of peptide 401 and of compound 48/80. 4. Injection of peptide 401 together with carrageenin increased the inflammatory response in the rat hind paw. 5. The anti-inflammatory activity of peptide 401 and of compound 48/80 in the carrageenin-induced swelling of the rat hind paw arises from mast cell degranulation in vivo. PMID- 2328400 TI - The central and regional cardiovascular responses to intravenous and intracoronary administration of the phenyldihydropyridine elgodipine in anaesthetized pigs. AB - 1. The central and regional cardiovascular responses to intravenous (0.3, 1.0, 3.0 and 10.0 micrograms kg-1 min-1) and intracoronary (0.3, 0.9, 3.0 and 4.5 micrograms kg-1 min-1) infusions of elgodipine, a phenyldihydropyridine, and its solvent were studied in anaesthetized pigs. 2. Elgodipine (i.v.) caused dose dependent decreases in arterial blood pressure (up to 44%) and systemic vascular resistance (up to 48%), whereas heart rate, LV dP/dtmax, left ventricular filling pressure, cardiac output and segment length shortening did not change. The absence of a negative inotropic effect with the employed doses was confirmed by the intracoronary infusions; with the lowest dose (0.3 micrograms kg-1 min-1) both LV dP/dtmax and segment length shortening decreased by less than 10%. With 0.9 micrograms kg-1 min-1 (intracoronary) the negative inotropic properties of the drug became apparent as LV dP/dtmax and segment length shortening decreased by 20% and 33%, respectively, whereas heart rate and left ventricular filling pressure were not affected. 3. Transmural myocardial blood flow did not change during intravenous infusion of elgodipine, as vasodilatation, more pronounced in the subepicardial than in the subendocardial layers, compensated for the decrease in arterial perfusion pressure. The intracoronary infusions revealed that the decrease in normalized subendocardial/subepicardial blood flow ratio was not secondary to the fall in arterial blood pressure. 4. Myocardial oxygen consumption decreased during both the i.v. and the intracoronary administration of elgodipine. With the i.v. administration the decrease was secondary to the hypotensive action of the drug, whereas with the intracoronary administration the negative inotropic properties played the dominant role. 5. Elgodipine (i.v.), although not affecting total cardiac output, caused a redistribution in favour of the nutritional blood flow at the expense of the arteriovenous anastomotic (AVA) blood flow. Up to an infusion rate of 3.0upg kg - I min- 1 the decrease in AVA flow was due to a fall in arterial blood pressure, but at the highest infusion rate both the decrease in arterial perfusion pressure and an increase in their resistance contributed to a further decrease in AVA blood flow. 6. The skeletal muscles benefited most from the elgodipine(i.v.)-induced increase in nutritional blood flow, but vasodilatation was not uniform for all muscle groups. Up to an infusion rate of 3 yg kg - ' min- 1 the vasodilatation in the renal vascular bed was more pronounced in the inner than in the outer cortex, but, at 0 pyg kg-1 min , vascular resistances of both cortical layers returned to baseline values. In all regions of the brain, blood flow was maintained until the highest infusion rate was given. With 10 yg kg- I min - ' only flow to the vital parts of the brain (diencephalon and brain stem) was maintained. Blood flows to the skin and various abdominal organs were well maintained up to 3 pg kg'- min - 1 but, at the highest dose, a decrease was observed in blood flow to the adrenals and spleen. Vascular resistances of all these organs and tissues decreased dose-dependently. 7. The potent systemic and coronary vasodilator actions of elgodipine during i.v. administration, which were not accompanied by negative inotropic and positive chronotropic properties or decreases in the perfusion of vital organs, warrant further study as this compound could be useful in the treatment of essential hypertension, myocardial ischaemia and, possibly, moderate chronic heart failure. PMID- 2328401 TI - Modulation of the reactivity of the guinea-pig isolated trachealis by respiratory epithelium: effects of cooling. AB - 1. Examination has been made of the effects of epithelium removal on the reactivity of guinea-pig trachealis to methacholine at 37 degrees C and 22 degrees C, and on responses to activation of the Na+/K(+)-pump by abrupt temperature increase from 22 degrees C to 37 degrees C. 2. At 37 degrees C, epithelium removal increased the sensitivity of isolated tracheal strips to methacholine without affecting the maximum isometric contractile response. Epithelium removal resulted at 22 degrees C in a decrease in sensitivity to methacholine, i.e. an effect opposite to that seen at 37 degrees C. While the maximum response of intact strips to methacholine was enhanced at 22 degrees C, the maximum response of denuded preparations was decreased. 3. The increase in sensitivity to methacholine at 37 degrees C after epithelium removal was mimicked in intact preparations by indomethacin (1 microM). Indomethacin did not mimic the decrease in methacholine sensitivity and maximum response caused by epithelium removal at 22 degrees C. 4. Following incubation at 22 degrees C, abrupt increase in temperature to 37 degrees C elicited relaxation in both epithelium-containing and epithelium-denuded tracheal strips. In epithelium-containing preparations the relaxation was more pronounced and followed by contraction. Ouabain (1 microM) converted the relaxation of denuded preparations to contraction, but was ineffective in intact strips. The relaxation of intact strips was, however, inhibited by a greater ouabain concentration (10 microM). 5. These findings indicate that the modulatory effect of the epithelium is temperature-dependent. In cooled preparations, the epithelium enhances reactivity. At 37 degrees C, an epithelium-derived factor reduces reactivity, and this may partially be due to activation of the electrogenic Na+/K+-pump. PMID- 2328402 TI - The role of the endothelium in mediating the actions of ATP, adenosine and acetylcholine on flow through blood vessels in the rabbit knee joint. AB - 1. An in vitro preparation of the rabbit knee joint, perfused with oxygenated Locke solution, was used to investigate the presence of purinoceptors and the role of endothelium within articular blood vessels. 2. The basal tone of the blood vessels was not affected by adenosine or acetylcholine. Adenosine 5' triphosphate (ATP) injection produced vasoconstriction which was unaffected by removal of the endothelial layer, but diminished by alpha, beta methylene ATP, a compound which desensitizes P2-purinoceptors. 3. When knee joint blood vessel tone was raised by perfusion with vasopressin (10(-8) M) or 5-hydroxytryptamine (10(-5) M), acetylcholine, ATP and adenosine were all found to induce concentration-dependent relaxation of these vessels. ATP was found to have a dual effect of transient constriction followed by longer-lasting dilatation. 4. 3 Methylxanthine, a P1-purinoceptor antagonist significantly reduced the relaxation response to adenosine but had no effect on the vasodilator effect of ATP. 5. Removal of the endothelial layer virtually abolished the vasodilator effects of acetylcholine and ATP but not adenosine. 6. These results demonstrate that articular blood vessels supplying the rabbit knee contain P1-purinoceptors located on the vascular smooth muscle which mediate vasodilatation. P2 purinoceptors mediating a constrictor effect are also present on this smooth muscle. It is likely that the vasodilator effect of ATP is mediated via P2 purinoceptors located on the endothelial layer. PMID- 2328403 TI - Prevention of non-specific airway hyperreactivity after allergen challenge in guinea-pigs by the PAF receptor antagonist SDZ 64-412. AB - 1. Allergen challenge by aerosol in sensitized guinea-pigs elicited non-specific airway hyperreactivity assessed by reactivity to i.v. histamine or acetylcholine. Airway hyperreactivity to histamine persisted for at least 48 h and was accompanied by pulmonary eosinophilia as determined by bronchoalveolar lavage cell analysis. 2. Airway hyperreactivity was independent of vagal reflex mechanisms since it was not abrogated by bilateral vagotomy. 3. The novel platelet-activating factor (PAF) receptor antagonist SDZ 64-412 inhibited the development of airway hyperreactivity, as measured 24 h after aerosol allergen challenge, when given as a single treatment orally 2 h before allergen challenge. The PAF receptor antagonist WEB 2086 as well as methylprednisolone and ketotifen also showed efficacy in preventing development of airway hyperreactivity. 4. Neither the two PAF antagonists nor ketotifen had any effect on bronchoalveolar lavage (BAL) eosinophil numbers. Methylprednisolone was the only substance which readily prevented eosinophil recruitment in addition to airway hyperreactivity. 5. We conclude that allergen-induced airway hyperreactivity in guinea-pigs is inhibited by prophylactic anti-asthma drugs and specific PAF receptor antagonists, thus demonstrating a pivotal role of PAF in this response. There was a lack of correlation between airway hyperreactivity and the presence of BAL eosinophils. PMID- 2328404 TI - L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. AB - 1. The effect of L-NG-nitro arginine (L-NOARG) was compared with that of L-NG monomethyl arginine (L-NMMA) on vasodilatation of the isolated aorta of the rabbit and perfused mesentery of the rat in response to acetylcholine (ACh) and sodium nitroprusside (NP). 2. L-NOARG (1.5-100 microM) and L-NMMA (3-100 microM) produced concentration-related contraction of the rabbit aorta precontracted with phenylephrine (700-900 nM). Similarly, L-NOARG (10-200 microM) and L-NMMA (30-100 microM) elevated perfusion pressure of the noradrenaline (NA, 0.6-2.5 mM) preconstricted rat mesentery preparation. 3. L-NOARG (1.5-100 microM) and L-NMMA (3-100 microM) caused concentration-related inhibition of the vasodilator effect of ACh (0.01-1.0 microM) on the rabbit aorta without influencing responses to NP (0.03-0.5 microM). L-NOARG methyl ester (30 microM) also inhibited ACh-induced vasorelaxation with similar potency to NOARG. L-arginine (30-150 microM) but not D-arginine (100 microM) caused graded reversal of the inhibitory effect of both L NOARG (15 microM) and L-NMMA (30 microM). Complete reversal of the effect of both inhibitors was achieved with 150 microM L-arginine. L-Alanine (50 microM), L arginosuccinic acid (5 microM), L-citrulline (50 microM), L-methionine (50 microM) and L-ornithine (50 microM) failed to reverse the inhibitory effect of L NOARG (15 microM). 4. L-NOARG (10-200 microM) and L-NMMA (30-100 microM) inhibited the vasodilator effect of ACh (0.006-18.0 nmol) in the rat mesentery without affecting vasodilatation due to NP (1.1-11.1 nmol). L-Arginine (100 microM) but not D-arginine (100 microM) produced partial reversal of the effect of L-NOARG (30 microM) and L-NMMA (30 microM). 5. L- and D-N'-butyloxycarbonyl No nitro arginine (100 microM) produced modest (approximately 20%) inhibition of the effect of ACh on the rabbit aorta; this effect was not reversible with L-arginine (100 microM). L-Namonocarbobenzoxy arginine (L-NMCA, 5O microM), L-N-NG dicarbobenzoxy arginine (L-NDCA, 5 microM) and L-NG-tosyl arginine (50 microM) were inactive. 6. These results identify L-NOARG as a potent, L-arginine reversible inhibitor of endothelium-dependent vasodilatation. The available data suggests that L-NOARG, like L-NMMA, inhibits endothelial nitric oxide (NO) biosynthesis. PMID- 2328405 TI - Simultaneous perfusion of rat isolated superior mesenteric arterial and venous beds: comparison of their vasoconstrictor and vasodilator responses to agonists. AB - 1. A new isolated perfused preparation is described that allows a direct comparison to be made of the responses of the perfused arterial and retrogradely perfused venous circulations of the rat superior mesenteric vascular bed. 2. In experiments comparing the responses of the intact arterially perfused mesentery and small intestine to those of the same preparation following removal of the intestine and division of the circulations, the increases in perfusion pressure produced by arginine-vasopressin (30 pmol) and noradrenaline (1 nmol) were retained by the arterial circulation and those induced by angiotensin II (30 pmol) by the venous circulation. Endothelin-1 (30 pmol) constricted both portions of the vasculature but the prolonged nature of its response was associated with only the venous vessels. 3. In the simultaneously perfused arterial and venous preparation arginine vasopressin (3-100 pmol) was a selective constrictor of the arterial circulation and angiotensin II (3-100 pmol) of the venous circulation. In addition, noradrenaline (0.3-10 nmol), 5-hydroxytryptamine (0.3-10 nmol) and KCl (1-60 micromol) were more active as constrictors of the arterial than the venous vessels, and U46619 (10-300 pmol) a more active constrictor of the venous than the arterial vessels. Endothelin-1 (3-100 pmol) constricted both the arterial and venous portions of the vasculature but was significantly longer acting as a venoconstrictor than an arterioconstrictor. 4. Angiotensin I (300 pmol) caused constrictions of the venous circulation which were dependent upon the presence of angiotensin converting enzyme for captopril (10 microM) abolished constrictions caused by angiotensin I but not by angiotensin II. 5. In preparations preconstricted by U46619 (0.3-3 microM), acetylcholine (0.01-100 nmol), bradykinin (0.001-nmol), sodium nitroprusside (0.01-lOnmol) or isoprenaline (1-l00pmol) produced dose-related dilatations of both the arterial and the venous vasculatures, whereas adenosine diphosphate (ADP, 0.01-lOOnmol) caused dose-dependent dilatations of the arterial circulation but principally constrictions of the venous circulation. The dilatations caused by acetylcholine and bradykinin in both portions of the circulation, and by ADP in the arterial circulation, were endothelium-dependent as they were inhibited by gossypol (3 microM), whereas dilatations to sodium nitroprusside were not. 6. This preparation allows the responses of the arteries and veins of a single perfused mesenteric bed to be compared. In addition, with this preparation it is possible to demonstrate that veins, as well as arteries, show significant endothelium dependent relaxations. It is concluded that the venous portion of the vasculature is significantly involved in the responses of the intact circulation. PMID- 2328406 TI - Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. AB - Brain MRI was performed on 12 patients with acute disseminated encephalomyelitis (ADEM). Multifocal white matter lesions indistinguishable from those seen in multiple sclerosis (MS) were found in 10. In 5 there were rather extensive symmetric abnormalities in the cerebral (2) or cerebellar white matter (2), or basal ganglia (1). Follow-up MRI after intervals of 2 wks to 18 months demonstrated partial resolution of the abnormalities, but some persisting lesions. New MRI lesions were found at follow-up in only 1 case after an interval of 2 wks. Serial MRI makes a useful contribution to the distinction between MS and ADEM. PMID- 2328407 TI - The corticospinal tracts in man. Course and location of fibres at different segmental levels. AB - The course, location and relations of the corticospinal tracts within the spinal cord of man are demonstrated on the basis of cases with lesions above the spinal cord restricted to the corticospinal tracts, of motor neuron disease, and of anterolateral cordotomies; control cases were of normal spinal cords. The following features of the lateral corticospinal tract are emphasized in the cervical cord: (1) the large extent of the white matter of the cord covered by the tract, and the anterior extent of the tract, the border being anterior to the central canal; (2) in the lower cervical cord, the separation of fibres from the main mass of the tract, which reach the periphery of the cord in the anterolateral sector; (3) the presence in many cords of the ventral crossed bundle; and (4) the relationship of the denticulate ligament to the tracts in the cervical segments. The following features of the anterior corticospinal tracts are emphasized: (1) their location, caudal extent and asymmetry; and (2) the changes in location in relation to the median fissure as the tract descends and its relationship to other tracts of the anterior column. Three-quarters of spinal cords are asymmetric and in three-quarters of asymmetric cords the right side is the larger. The asymmetry is due to a greater number of corticospinal fibres crossing to the right side. As more fibres have crossed in the decussation, the anterior tract opposite the large lateral tract is smaller than the ipsilateral anterior tract: that accounts for the asymmetry of the two halves of the cord. The greater number of corticospinal fibres in the right side of the cord is unrelated to handedness, but correlates with the fact that in three-quarters of corticospinal decussations, the crossing from left to right occurs at a more cranial level than the opposite crossing. A group of short peripheral ascending fibres is described running along the sides of the median fissure in the thoracic cord. PMID- 2328408 TI - Hereditary motor system diseases (chronic juvenile amyotrophic lateral sclerosis). Conditions combining a bilateral pyramidal syndrome with limb and bulbar amyotrophy. AB - Forty-three patients with hereditary motor system diseases belonging to 17 families were studied. The clinical features consisted of a bilateral pyramidal syndrome, weakness with atrophy and fasciculation of the hands and/or the legs, with or without a bulbar or a pseudobulbar syndrome and without sensory disturbance. Electromyography in 31 cases (including all index cases) showed evidence of denervation. Motor and sensory nerve conduction velocity was normal; sensory nerve action potential amplitudes, examined in 11 cases, were also normal. Nerve and muscle biopsies taken in 29 cases (including all index cases) showed neurogenic atrophy in the peroneus brevis muscle and minor changes only in the superficial peroneal nerve. The mean age of onset was 12.06 (range 3-25 years), and progression was very slow. Inheritance appeared to be autosomal recessive. Depending on the clinical presentation, the patients were subdivided into three groups comprising (1) upper limb and sometimes bulbar amyotrophy with a bilateral pyramidal syndrome (17 patients: 11 familial and 6 isolated); (2) spastic paraplegia with peroneal muscular atrophy (14 patients: 11 familial and 3 isolated); and (3) a spastic pseudobulbar form (12 patients in a large kinship). These entities are discussed and compared with other cases reported in the literature. PMID- 2328410 TI - Semantic memory loss in dementia of Alzheimer's type. What do various measures measure? AB - This paper examines three methodological issues concerning the measurement of semantic memory impairment in brain-damaged patients. Ten carefully selected patients with dementia of Alzheimer's type (DAT) and anomia were studied. A battery of perceptual tests and direct tests of semantic memory led to the conclusion that these patients represented a homogeneous group having a prominent deterioration of their semantic memory store without visual perceptual deficits. The first issue addressed in this patient group was whether verbal fluency impairment accurately reflected the loss of semantic memory. It was found that verbal fluency (generation of semantic category lists) was impaired due to two major constraints: deterioration of semantic memory store, and variable difficulties in semantic search. Verbal fluency, therefore, reflects semantic memory loss to some degree, but is not a direct test of semantic memory store in DAT. The second issue was whether semantic memory impairment in our patients conformed to the 'semantic storage disorder' syndrome hypothesized by Shallice (1987). It was shown that, consistent with this hypothesis, the patients demonstrated co-occurrence of consistency of errors, loss of semantic cueing, and preserved superordinate knowledge with loss of detailed knowledge of concept items. The third issue was whether semantic cueing and semantic priming are altered in a similar manner in DAT. It demonstrated that semantic cueing and semantic priming, using the same words whose concepts were degraded in semantic memory, yielded an entirely different pattern of results. Cueing and priming therefore may not be used interchangeably in the study of semantic loss after brain damage. PMID- 2328409 TI - Duration and selectivity of blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis studied by gadolinium-DTPA and protein markers. AB - Gadolinium-DTPA (Gd-DTPA) enhancement seen with magnetic resonance imaging in chronic relapsing experimental allergic encephalomyelitis (CREAE) corresponded with sites of blood-brain barrier breakdown judged by traditional markers in areas of inflammatory demyelination. Duration of Gd-DTPA leakage for individual lesions in CREAE varied from 5 days to more than 5 wks. By contrast, in acute EAE leakage was of shorter duration (always less than 5 days). Selective enhancement was observed in CREAE lesions using Gd-protein markers. Gd-albumin enhancement was not always seen in areas of leakage of the smaller molecular weight compound Gd-DTPA. The addition of immunoglobulin to the gadolinium complex led to enhancement of lesions not seen with Gd-albumin alone. From the similarities between the histology and the patterns of Gd-enhancement in CREAE and multiple sclerosis, it is probable that Gd-enhancement reflects active inflammation (with or without demyelination) in the human disease. PMID- 2328411 TI - A mitochondrial encephalomyopathy with specific deficiencies of two respiratory chain polypeptides and a circulating autoantibody to a mitochondrial matrix protein. AB - A 15-yr-old boy with mitochondrial encephalomyopathy and NADH CoQ reductase (Complex I) deficiency is presented. Immunoblotting demonstrated specific deficiencies of the 24 kDa FeS protein of Complex I and subunit II of Complex IV. The patient's serum contained an antibody to a specific mitochondrial matrix polypeptide of apparent Mr 41 kDa. The specific polypeptide deficiencies involve products of nuclear (24 kDa FeS protein) and mitochondrial (subunit II) genes and suggest some intergenomic regulation. The relevance of the circulating antibody to the pathogenesis of the patient's Complex I deficiency is discussed. PMID- 2328412 TI - Acute infantile spinal muscular atrophy. Muscle apoptosis as a proposed pathogenetic mechanism. AB - Biopsy as well as autopsy studies of a child who died 8 weeks after birth from the acute infantile form of spinal muscular atrophy revealed classical morphological changes, including degeneration and loss of motoneurons in the spinal cord, loss of large myelinated fibres in anterior roots and neurogenic atrophy in muscle. New ultrastructural findings include massive muscle cell elimination by apoptosis with the formation of membrane-bound muscle cell fragments, apoptotic bodies. In addition, numerous immature muscle fibres were observed. The morphological findings raise the possibility that in a severely growth-retarded muscle, the process of muscle cell apoptosis removes the peripheral target of anterior horn cells resulting in secondary motoneuron death. PMID- 2328413 TI - Disorders of eye movement in myotonic dystrophy. AB - Horizontal saccades and smooth pursuit eye movements were studied in 26 patients with myotonic dystrophy. Clinical neuro-ophthalmological investigations in 1 patient revealed an inability to achieve a full range of eye movements. Electro oculography showed a significant decrease of the maximum velocity of the visually guided saccades in 83% of the patients. Smooth pursuit eye movements were not significantly different from age-matched controls. Visual evoked potential (VEP) latencies (P100) were significantly prolonged compared with controls in 64% of the patients. The saccadic latency of the visually-guided saccades was correlated with the prolonged VEP latencies, indicating that lesions in the primary visual pathways probably contribute to the oculomotor dysfunction. The isolated decrease of the maximum velocity of the saccades in combination with EMG findings favours a peripheral (dystrophic) pathophysiological mechanism. PMID- 2328414 TI - Directional hypokinesia and hemispatial inattention in neglect. AB - Subjects with neglect of left hemispace may err to the right when bisecting lines. This error has been attributed either to a directional hypokinesia (failure to execute movements fully in or towards the contralateral hemispace) or to a failure to attend to or represent sensory information. Four subjects with neglect were tested on a line bisection task in which these two hypotheses were differentiated by preventing direct viewing of the line and instead using a video camera and monitor, each of which could be moved independently into right or left hemispace. The performance of 2 subjects was consistent with the predictions of the directional hypokinesia hypothesis; the performance of the other 2 subjects was consistent with the attention-representation deficit hypothesis. These data suggest that both a directional hypokinesia and an attention-representation deficit may each be a primary determinant of neglect. PMID- 2328415 TI - Optic neuritis: variations in temporal modulation sensitivity with retinal eccentricity. AB - Temporal modulation sensitivity functions were measured centrally and at eccentricities of 2.5 degrees, 5 degrees and 10 degrees in the temporal visual field of 12 patients with recovered optic neuritis and in a group of matched normal controls. A circular, spatially uniform stimulus of 1 degree angular subtense was presented with sinusoidal modulation at 5, 8, 14 and 23 Hz. The general pattern of results in patients was a loss of sensitivity relative to normal controls at all temporal frequencies at 0 degree and 2.5 degrees eccentricity, with rather greater losses occurring at the medium-to-lower temporal frequencies. At 5 degrees eccentricity, the losses were confined to medium temporal frequencies only, and at 10 degrees eccentricity there was no significant loss at any temporal frequency. These findings may be explained by a greater vulnerability of optic nerve fibers of small diameters to the effects of demyelinating disease. PMID- 2328416 TI - Histometric characteristics and regenerative capacity in wobbler mouse motor neuron disease. AB - In wobbler mice, histometric features and the response to injury in the less affected hindlimb nerves were compared with the severely affected forelimb nerves which were studied previously. The frequency of vacuolated anterior horn cells was not different at the individual ages studied (3 and 6 weeks, 3 months), but with the three ages combined, the frequency in the two systems differed significantly, being 1.7 +/- 0.9% in the cervical and 0.6 +/- 0.7% in the lumbar anterior horns (P = 0.005). The number of large myelinated nerve fibres (greater than or equal to 6 microns in diameter) became progressively reduced in ventral roots as the disease advanced, particularly for the forelimb. The total number of myelinated axons was well preserved in the hindlimb ventral roots because of an increase in the number of small myelinated nerve fibres. The regenerative capacity of motor neurons after axotomy (tested by radiolabelling growth cones) was well preserved. In the hindlimb, the increased numbers of small myelinated fibres in ventral roots and the normal regenerative capacity in the sciatic nerve and its branches contrast with the severely affected forelimb system. Our studies suggest that cervical and lumbar anterior horn cells have different susceptibilities to the wobbler gene, producing vulnerability in one system and disease resistance in the other. PMID- 2328417 TI - Furtive incursions into bicameral minds. Integrative and coordinating role of subcortical structures. AB - Section of forebrain commissures results in a pervasive disconnection syndrome characterized by the incapacity of the two cerebral hemispheres to exchange their respective information content. Yet commissurotomized patients are capable of unified behaviour in their daily activities and, in laboratory situations, are able to produce a single response as a function of the information received by both hemispheres. This study further investigated the nature of the information that can be communicated between the disconnected hemispheres in 3 commissurotomized patients. The first part comprised 7 experiments in which the patients were required to compare 2 digits simultaneously, 1 projected to each hemisphere. While the stimulus and experimental conditions were the same across experiments, the information content on which to base the comparison was manipulated. The level of performance varied as a function of the information content, such that the patients were unable to decide whether the 2 digits were the same or different, performed better when required to compare the digits in terms of their odd-even category, and were highly accurate at deciding which digit was the higher. In addition, when instructed to focus on the numerical value of the digits to decide whether the 2 digits were the same or different, they performed significantly above chance. In the second part, they were requested to report verbally information about emotional faces and familiar faces projected to the right hemisphere. While they were unable to access the visual characteristics and the identity of the faces, they could provide various correct items of semantic information about the individuals. Taken together, the results indicate that the disconnection syndrome is limited to specific categories of information and does not extend to all the knowledge that may be derived from a given object. They also suggest that subcortical structures do not serve simply as pathways linking the two hemispheres but play an essential coordinating role in the integration of hemisphere activity. PMID- 2328419 TI - Design of combined treatment trials. PMID- 2328418 TI - Legionella lung cavitation. AB - Pneumonia due to Legionella has been identified in a small percentage of patients suffering from acquired immune deficiency syndrome (AIDS), with and without coexisting Pneumocystis carinii pneumonia. On chest radiographs Legionella typically produces focal parenchymal opacities and confluent lobar consolidation. The authors describe a case of cavitating Legionella pneumonia, which occurred in a 38-year-old man who had AIDS. The main differential diagnoses are an unusual presentation of P. carinii pneumonia and fungal infection. The authors also emphasize the increasing recognition of bacterial pneumonia with atypical radiologic features in AIDS patients. PMID- 2328420 TI - Zero-added-dose gastrointestinal film studies: update. PMID- 2328421 TI - Social conscience, social action. PMID- 2328422 TI - Regional bone mineral measurements. AB - Total body dual-photon transmission scanning was performed in 9 control persons, 15 athletes and in 5 patients with eating disorders. Total body bone mineral mass was measured, with a reproducibility of 2%; for regional bone mineral mass the reproducibility was 4%. The fraction of total bone mineral in the spines and heads of women is greater than in men. Patients with eating disorders have a smaller fraction of total body mineral in the pelvis than female controls. Weight lifters have a significantly greater mineral mass in the trunk region than other athletes and male controls. These and other differences are consistent with the conclusion that total body dual-photon absorptiometry allows quantitation of the distribution of mineral within the skeleton. PMID- 2328423 TI - Fine-needle aspiration of bone lesions. AB - Percutaneous needle biopsy of bone lesions has been done for over 50 years. Although initially not widely used, it has been increasingly accepted over the past several years. Large-bore needles were used at first. However, as cytopathological techniques have improved, fine-needle biopsy has become feasible, offering the advantage of reduced tissue trauma and increased flexibility in needle positioning. We have retrospectively reviewed our fine needle bone biopsies performed from January 1985 to May 1988 in 53 patients. Repeat aspirations were required on only five patients. Adequate samples were obtained at initial biopsy in the remainder. Accuracy was 0.94 which is comparable with, or better than, reported results obtained using larger bone needles. Accuracy was not affected by site or number of lesions, nor was it markedly different in patients with and without known primary malignant lesions. Biopsy of bone lesions using a fine needle provides a flexible, accurate, and relatively atraumatic alternative to more invasive methods. PMID- 2328424 TI - Osteomyelitis of the tarsal bones in children. AB - The radiographic findings in seven children with tarsal osteomyelitis are described. The bones involved were the calcaneus, talus, cuboid, and navicular. The lesions appeared as single, subchondral, reasonably well-defined round lucencies measuring up to 12 mm in diameter. Bone scans were positive. The lesions healed slowly with surrounding sclerosis but no periosteal reaction. PMID- 2328425 TI - Atypical radiographic appearances of tuberculous granulomas of bone. AB - We present four adults with tuberculous granulomas of bone. In three patients the granuloma involved the end of a long bone. The vertebral body and the right pedicle of the 10th thoracic vertebra were involved in the fourth patient. In all four the adjacent joint or the disk space was spared; hence the lesions mimicked bone neoplasms. Sclerotic changes, periosteal reaction and sequestration were present in three patients. Three of the four patients were not white. Since histologic specimens may not reveal mycobacteria, radiologists should alert orthopedic surgeons to the need to obtain material for culture at the time of biopsy of lesions that might be unusual manifestations of skeletal tuberculosis. PMID- 2328426 TI - Mediastinal hydatid disease: report of three cases. AB - We report three patients who had mediastinal echinococcosis and then review the literature. The first patient had a primary anterior mediastinal echinococcal cyst, the second a mediastinal hydatid cyst, secondarily involving the mediastinum and mimicking Hodgkin's disease, and the third had a primary cardiac and pericardial hydatid cyst. In two patients computed tomography (CT) was helpful in making a preoperative diagnosis before any complication could arise. In the third CT was not done and the diagnosis of cardiac echinococcosis at surgery was a surprise. Two large echinococcal cysts compressing the ventricles, which on echography and cardioangiography had the appearance of endomyocardial fibrosis, were removed by total excision. The disease in each patient was correlated with clinical and radiologic findings and was confirmed by tissue microscopy. PMID- 2328427 TI - Focal brain lesions on computed tomography in patients with acquired immune deficiency syndrome. AB - Neurologic involvement is common in patients with acquired immune deficiency syndrome (AIDS). To assess the computed tomographic findings in AIDS, the authors reviewed 12 consecutive patients found to have focal brain lesions representing AIDS complications on computed tomography and having histologic or clinical proof of the diagnosis. Five patients had toxoplasmosis, six had lymphoma and one had both conditions sequentially. The finding of multiple lesions and mass effects with edema was more common with toxoplasmosis. In six patients who had toxoplasmosis 33 nodules were observed compared with only 8 in seven patients who had lymphoma. Disease extending linearly along the ventricular wall was typically seen in patients who had lymphoma. PMID- 2328428 TI - Fibrovascular polyp of the esophagus with computed tomographic and pathological correlation. AB - The authors report a patient with a fibrovascular polyp of the esophagus. Radiologic and pathological features of this rare tumor include computed tomographic findings of a lesion of low density, situated intraluminally so that the findings may be relatively specific. PMID- 2328429 TI - Multimodality imaging of early heterotopic bone formation. AB - An atypical heterotopic bone formation that was difficult to diagnose presented in a young paraplegic patient as an acute deep vein thrombosis. A number of imaging methods, including contrast venography, ultrasonography, conventional radiography, bone scanning, leukocyte scanning, computed tomography, and magnetic resonance imaging, were used to arrive eventually at the final diagnosis. Early bone scanning remains a sensitive and effective method of diagnosis. Computed tomography can be useful in difficult cases, but the role of other imaging studies appears limited. PMID- 2328430 TI - Haemophilus influenzae abscess presenting as an asymptomatic lung mass. AB - We report the radiographic and computed tomographic findings in an asymptomatic patient who had a Haemophilus influenzae lung abscess. The diagnosis was made by Gram's staining and culture of abscess material obtained by transthoracic needle aspiration. The radiographic abnormalities cleared after specific antimicrobial therapy. PMID- 2328431 TI - Clinical management of orbital cellulitis in children. AB - A prospective study was carried out by the Department of Ophthalmology and the Division of Infectious Disease at the Children's Hospital of Eastern Ontario to assess the outcome of our medical management of orbital cellulitis in children using a predetermined antibiotic regimen and to determine whether computed tomographic (CT) evidence of a subperiosteal abscess alone was an indication for surgical drainage. Between February 1985 and January 1988, 23 patients with true orbital cellulitis were admitted. CT scans were ordered routinely at the time of admission. The scans were cancelled for 13 children because they responded rapidly to medical management. CT showed edema nasal to the medial rectus, or thickening or displacement of the muscle in 8 of the 10 children who underwent the procedure. Three children required sinus and orbital drainage, but frank purulent material was found subperiosteally in only one. The results suggest that most children with orbital cellulitis can be managed with the prompt use of the appropriate intravenous antibiotics. Therapy with cloxacillin sodium and chloramphenicol or, in children under age 6 years, cefuroxime best covers the spectrum of organisms responsible for most cases of orbital cellulitis in children. CT should be used as an ancillary guide to the need for surgical exploration of the orbit in patients who do not rapidly respond to medical management. PMID- 2328432 TI - Superior oblique palsy: diagnosis and treatment. AB - To pinpoint the diagnostic dilemmas and to look for differentiating preoperative features in cases of masked bilateral superior oblique palsy, the authors reviewed the charts of 50 patients (26 males and 24 females with an average age at presentation of 25.6 years) with an established diagnosis of superior oblique palsy seen between 1980 and 1987. Most patients had a history of symptoms from childhood or following trauma. Typically, patients complained of torticollis and diplopia and manifested inferior oblique overaction and superior oblique underaction of the paretic eye. Twenty-two of the patients underwent a total of 28 operations; surgery resulted in elimination of symptoms and neutralization of the hyperdeviation in 77%. On the basis of this experience the authors discuss the presenting features and the differential diagnosis of superior oblique palsy and present a rational approach to surgical intervention. PMID- 2328433 TI - Acanthamoeba keratitis in a soft-contact-lens wearer. AB - Acanthamoeba keratitis is an uncommon but potentially devastating complication of contact lens wear. We present a case of Acanthamoeba keratitis in a soft-contact lens wearer successfully treated with long-term medical therapy and penetrating keratoplasty. To our knowledge this is the first case of Acanthamoeba keratitis diagnosed in Canada. PMID- 2328434 TI - Endophthalmitis caused by exogenous nocardial infection in a patient with Sjogren's syndrome. AB - A 60-year-old woman receiving prednisolone therapy for Sjogren's syndrome presented with corneal perforation. Therapeutic penetrating keratoplasty was performed, but no causative organism was identified. Focal inflammatory infiltrates in both donor and host cornea and anterior uveitis developed postoperatively. Five months later the inflammation rapidly became much worse, with fulminating abscesses, and the eye was eviscerated because of severe endophthalmitis. Nocardia organisms were identified in the cornea, conjunctiva and vitreous by means of acridine orange and modified Ziehl-Neelsen stains. The infection produced both suppurative and granulomatous inflammation. Reexamination of the penetrating keratoplasty specimen with a modified Ziehl-Neelsen stain revealed a few Nocardia organisms, which suggested that infection had occurred at the time of corneal perforation. PMID- 2328435 TI - Variable expressivity in X-linked congenital stationary night blindness. AB - X-linked congenital stationary night blindness (CSNB) is a well-documented disorder in which the most striking clinical features are impaired night vision, nystagmus and myopia. Recent reports have highlighted differing features between families, and it has been suggested that these discrepancies may be the result of two loci on the X chromosome or of two mutant alleles. We outline the clinical and visual function findings in 42 affected members from 10 families and 1 adopted person. There was a relative unawareness of the disorder in clinical practice. At least one of the main features of CSNB was absent in 75% of the patients. The visual function values varied widely, both between and within families (visual acuity 20/30 to 20/400, refractive error +1.50 to -22.50 and rod segment elevation 1.5 to 3.0 log units). The findings are consistent with a single allele exhibiting a wide variation in clinical expression. PMID- 2328436 TI - Amelanotic malignant melanoma of the conjunctiva with local metastasis to the eyelid. AB - Conjunctival melanomas are uncommon. The amelanotic variety is extremely rare. We describe a patient with an amelanotic melanoma of the superior conjunctiva that was primarily excised, followed by extensive conjunctival resection and liquid nitrogen cryotherapy applied to the tumour bed. Eight months later a local metastatic lesion was noted in the lower eyelid. Eyelid metastasis in conjunctival melanoma is uncommon but may occur owing to the rich lymphatic vasculature within the conjunctiva. PMID- 2328437 TI - External ophthalmomyiasis associated with herpes zoster ophthalmicus. AB - Ophthalmomyiasis is a rare entity caused by infestation with certain dipterous larvae. We describe a 71-year-old farmer with herpes zoster ophthalmicus on the left side of the face in whom the blisters became secondarily infested with Chrysomyia bezziana maggots. The maggots were removed mechanically, and the corneal involvement secondary to zoster ophthalmicus responded to therapy with topical steroids and cycloplegics. To our knowledge this is the first report of external ophthalmomyiasis due to C. bezziana. PMID- 2328438 TI - Endothelial cells inhibit the vascular response to adrenergic nerve stimulation by a receptor-mediated mechanism. AB - Rabbit central ear arteries, with and without endothelium, were perfused at a constant flow rate and the perfusion pressure was measured as an index of the vessel resistance. Transmural nerve stimulation (TNS) induced a frequency dependent increase in perfusion pressure in all vessels that was blocked by tetrodotoxin, phentolamine, and prazosin. Removal of endothelium significantly enhanced contractions induced by TNS. The inhibitory effect of endothelium was not modified by indomethacin but was abolished by hemoglobin, indicating that endothelium-derived relaxant factor (EDRF) was the vasodilator involved. The endothelium-dependent inhibitory effect (rubbed vessel minus control vessel contractions) increased with time during the first 10-20 s after the beginning of TNS, and was frequency dependent and inhibited by low doses of phentolamine, which suggest a receptor-mediated mechanism. To analyze whether amine neurotransmitters are able to permeate the artery wall and contact the endothelial cell membrane, the passage of [3H]acetylcholine from the abluminal side to the lumen was studied in intact vessels. [3H]acetylcholine readily permeated the vessel wall, as assessed by radioautography, and appeared in the perfusion fluid at a concentration that explains the relaxation induced by perivascular acetylcholine. These data suggest that endothelial cells modulate the effect of perivascular neurotransmitters by a receptor-mediated mechanism. In the case of the sympathetic innervation, such modulation would be more relevant at low levels of transmitter release and would be minimized during intense sympathetic stimulation. PMID- 2328439 TI - Flow-induced oxygen uptake by the perfused rat hindlimb is inhibited by vasodilators and augmented by norepinephrine: a possible role for the microvasculature in hindlimb thermogenesis. AB - Oxygen uptake in the perfused rat hindlimb was studied at 25 degrees C using an artificial perfusate, and the effects of perfusate flow rate, norepinephrine, and vasodilators were compared. Hindlimb oxygen uptake and perfusion pressure each increased as the flow rate was increased stepwise from 2 to 18.5 mL/min per hindlimb. At each flow rate, the rate of oxygen uptake was inhibited by the vasodilator nitroprusside (0.5 mM) and increased by norepinephrine (5 nM). A corresponding change in perfusion pressure also occurred, with norepinephrine leading to a marked increase and nitroprusside leading to a decrease; however, changes in oxygen uptake and pressure were not linearly related. The lactate/pyruvate ratio of the perfusate was used as an index of tissue perfusion and was determined at each flow rate. Lactate and pyruvate efflux increased as the flow rate was increased stepwise from 2 to 18.5 mL/min per hindlimb. At 2 mL/min per hindlimb, the lactate/pyruvate ratio was 15; at flow rates equal or greater than 4 mL/min per hindlimb, the ratio was constant at 9. Nitroprusside had no significant effect on the ratio at any flow rate even though a marked inhibitory effect on oxygen uptake was evident. Muscle content of high energy phosphates at 8 mL/min per hindlimb did not differ before and after treatment with vasodilators. In addition, the vasodilators had no apparent effect on skeletal muscle oxygen uptake or force development during electrical stimulation. The findings indicate that oxygen uptake by the hindlimb is not limited by inadequate perfusion and that oxygen uptake can be further increased by norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328440 TI - Neural network control of simple limb movements. AB - It is possible to embed the control and computation of a simple single-joint movement at different speeds by a small non-linear network of neuron-like elements. The network "learns" by appropriate adjustment of the strengths of interconnection, or synaptic weights, between the neuron-like elements. The learning of a few movement trajectories is generalized to the learning of a family of unlearned trajectories. These observations are in support of our hypothesis that relaxation of a network from an initial state to a final equilibrium state is both causal and computational to movement generation and control. PMID- 2328441 TI - The effect of cyclosporine A on bile secretion in dogs. AB - Cyclosporine A is reported to cause cholestasis, but the evidence is confounded by anesthesia and surgery used in acute experiments. To better investigate the effect of cyclosporine on the liver, bile output was directly measured in three cholecystectomized dogs by cannulating the common duct through a chronic duodenal fistula. Control studies were done 1 month after surgery. Cyclosporine in oral doses of 5, 15, and 50 mg.kg-1.d-1 was then given for consecutive 1-week periods. Twice during each study period, bile output was measured for 5 h in fasted, awake animals: 3 h to establish basal conditions, followed by 2 h of taurocholate infusions at 1 and then 2 mumols.kg-1.min-1. Under basal conditions, bile flow rose with each dose of cyclosporine, increasing 63, 127, and 179% above control with cyclosporine 5, 15, and 50 mg.kg-1,d-1, respectively. Bile flow increased similarly during taurocholic acid stimulation. Cyclosporine had no effect on bile salt or bilirubin secretion. In this chronic dog model isolated from other causes of cholestasis, cyclosporine did not induce cholestasis but rather caused a dose related choleresis without any change in bile salt secretion. PMID- 2328442 TI - Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies. AB - Chronic, rapid ventricular pacing produces congestive heart failure in dogs. The objectives of this study were to determine whether or not (i) in vitro myocardial biochemical alterations reported for heart failure by volume or pressure overload also occurred with heart failure due to rate overload, and (ii) these biochemical alterations were related to relevant in vivo cardiac physiologic alterations. We compared 27 dogs that were paced to advanced heart failure with 21 sham-operated dogs. Dogs with heart failure had 55% lower left ventricular ejection fraction (22.5 +/- 7.6 vs. 50.5 +/- 5.1%) and cardiac index (81 +/- 22 vs. 178 +/- 48 mL.min-1.kg-1), 287% higher pulmonary capillary wedge pressure (27.5 +/- 6.8 vs. 7.1 +/- 3.4 mmHg; 1 mmHg = 133.3 Pa), and 64% greater left ventricular diastolic area (18.4 +/- 3.7 vs. 11.2 +/- 1.3 cm2) (all p less than 0.05). Dogs with heart failure also had (i) 69% lower norepinephrine (232 +/- 139 vs. 747 +/- 220 ng/g protein), (ii) 25-50% lower activities of myofibrillar Ca ATPase (0.188 +/- 0.026 vs. 0.253 +/- 0.051 U/mg myofibrils), sarcoplasmic reticulum Ca-transport ATPase (0.155 +/- 0.074 vs. 0.288 +/- 0.043 U/mg membrane), and the glycolytic enzyme phosphofructokinase (33.4 +/- 10.0 and 47.7 +/- 15.8 U/g), (iii) 32% higher activity of the beta-oxidation enzyme hydroxyacyl-CoA dehydrogenase (11.43 +/- 1.48 vs. 8.67 +/- 1.70 U/g), and (iv) 60% higher activity of Krebs cycle oxoglutarate dehydrogenase (2.89 +/- 0.77 vs. 1.81 +/- 0.95 U/g) (all p less than 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328443 TI - The relationship between post-tetanic potentiation of motor units and myosin isoforms in mouse soleus muscle. AB - Post-tetanic potentiation was measured in motor units, isolated functionally by ventral root splitting, of soleus and extensor digitorum longus muscles of mouse. All motor units from the extensor digitorum longus had times to peak twitch tension less than 13 ms; there was a linear relationship between time to peak tension and post-tetanic potentiation, with the faster units exhibiting greater potentiation. When soleus motor units were similarly analyzed, it appeared that there may be two distinct populations of units. Those units with times to peak tension less than 13 ms were virtually indistinguishable from those of extensor digitorum longus. On the other hand, the slope of the relationship between post tetanic potentiation and time to peak tension was significantly lower for soleus units with times to peak tension of 13 ms or more. Approximately three-quarters of the soleus units were of the latter slow type, whereas only one-half of the muscle fibres could be classified as type I by means of immunohistochemistry, suggesting that the myosin heavy chain may not be the major determinant of post tetanic potentiation. Single, chemically skinned fibres of soleus were analyzed for myosin heavy and light chain components by polyacrylamide gel electrophoresis. All fibres with type I heavy chain contained only the two slow light chains. On the other hand, almost all of the fibres with type IIA myosin heavy chain contained both fast and slow light chains. It is suggested that the discrepancy between the proportions of physiologically "fast" motor units and histochemical type IIA fibres may be the consequence of variable amounts of slow light chain associated with the fast IIA myosin heavy chain. PMID- 2328444 TI - Uptake and methylation of histamine by dispersed gastric mucosal cells and its possible influence on acid secretion. AB - Inactivation of histamine by gastric mucosal tissue was examined in dispersed rabbit gastric mucosal cells. Mucosal cells were incubated with [14C]histamine. The formed radioactive metabolites were separated and identified by thin layer co chromatography and quantitated, in both the cellular and extracellular mediums. Gastric mucosal cells internalized histamine, most of which was immediately methylated primarily to N tau-methylhistamine and released. Cellular histamine product accumulation reached a plateau. The rate of histamine methylation increased with increasing extracellular histamine concentration, moving towards a plateau above 5 microM. Histamine methylation was greatly decreased but not abolished at 4 degrees C, in the absence of Na+ and by phlorizin (0.5 mM), an inhibitor of Na(+)-dependent co-transport. Inhibition of histamine N methyltransferase decreased intracellular methylhistamine content dose dependently without increasing intracellular histamine. The secretagogues pentagastrin and carbachol did not influence histamine metabolism but ethanol inhibited methylation. The data suggest that gastric mucosal cells take up histamine by a Na(+)-dependent and Na(+)-independent process. The histamine uptake capacity appears to be linked to the methylation activity within the cell. The decrease in histamine uptake and metabolism caused by ethanol could potentially increase histamine concentrations near the target cells and be the reason for the stimulatory effect of ethanol on acid secretion. PMID- 2328445 TI - Effect of metabolic acidosis on glucose reabsorption in rats with acute hyperglycemia. AB - The rate of reabsorption of glucose in the kidney is a factor to consider with respect to the degree of hyperglycemia in poorly controlled diabetics. The rate of reabsorption of glucose in the proximal tubule is driven by the electrochemical gradient for sodium across the luminal membrane. This gradient in the proximal tubule is also used to reabsorb a number of other substances, quantitatively the most important being bicarbonate. We wished to explore the hypothesis that acidosis, by reducing the filtered load of bicarbonate and therefore the reabsorption of bicarbonate in the proximal tubule, might permit an increased rate of reabsorption of glucose. Hyperglycemia was induced in rats by the infusion of hypertonic glucose. Reabsorption of glucose was measured by clearance methods and factored for glomerular filtration rate (GFR), which has a direct effect on the reabsorption of glucose. The reabsorption of glucose was increased in the kidney when the reabsorption of bicarbonate in the proximal tubule was decreased by either HCl-induced acidosis or the administration of a carbonic anhydrase inhibitor. This effect was independent of a change in GFR and the fractional excretion of Na, factors that may also lead to changes in the reabsorption of glucose by the kidney. PMID- 2328446 TI - Dose-dependent inhibition of cyclosporine metabolism in mice by fluconazole. AB - Fluconazole, a potent bis-triazole antimycotic drug, has been demonstrated to inhibit antipyrine metabolism, a cytochrome P-450 dependent process, in vivo in mice. Cyclosporine is metabolized by the cytochrome P-450 enzyme system in both mice and man. We investigated whether fluconazole had any effects on the metabolism of cyclosporine in vivo in mice. The effects of three different doses of fluconazole (1, 5, and 20 mg/kg) on the metabolism of cyclosporine in CD-1 mice were studied in single-dose experiments. Fluconazole produced significant dose-dependent decreases in the elimination rate constant and increases in the terminal half-life of cyclosporine. The 1 mg/kg dose caused a 26% prolongation of the terminal half-life and the 5 and 20 mg/kg dose prolonged the half-life by 72 and 187%, respectively. Fluconazole doses in the 1-5 mg/kg range are effective in mouse models of fungal infections. These results provide further in vivo evidence that fluconazole is a potent inhibitor of the cytochrome P-450 dependent enzyme system in mice. Future experimental studies in animals and humans are needed to evaluate possible metabolic drug-drug interactions involving fluconazole. PMID- 2328447 TI - Response to pinealectomy and blinding in vitellogenic female frogs (Rana perezi) subjected to high temperature in autumn. AB - The present experiments were carried out to investigate the effects of pinealectomy and bilateral enucleation on the ovarian activity in Rana perezi frogs maintained in 12-h light--12-h dark photoperiod and 20 +/- 1 degrees C during the vitellogenetic growth in late autumn. These environmental conditions, mainly temperature, induce a gonadal and metabolic response similar to that observed in the natural habitat in summer: a marked ovarian follicular regression, a depletion of the energetic resources from fat bodies and liver, and a minimum in oestradiol circulating levels. This response is partially blocked by pinealectomy and blinding. Protein phosphorus, as an index of vitellogenic proteins, and total ovary lipid content were significantly higher in pinealectomized and blinded frogs with respect to sham-operated animals. Likewise, oestradiol concentrations showed a significant increase during the dark phase of the daily photocycle in pinealectomized and blinded animals. From our results, we can suggest that the arrest of vitellogenesis, the depletion of energetic resources, and the regulation of oestradiol levels induced by the high temperature in Rana perezi frogs can be influenced, at least in part, by the pineal complex and lateral eyes. PMID- 2328448 TI - Effects of chronic nicotine treatment on nicotinic receptors in the rabbit urinary bladder. AB - Nicotine induced a phasic contraction in the rabbit urinary bladder. The response was abolished by hexamethonium and partially reduced by atropine and capsaicin. Simultaneous atropine and capsaicin treatment did not abolish the contraction. These findings suggest that the response to nicotine is due to acetylcholine, tachykinins, and unknown mediator release. In contrast, nicotine-induced contraction diminished following the chronic nicotine treatment without a change of its pharmacological properties. These results suggest the possibility that chronic nicotine treatment causes a decrease in nicotinic receptor numbers. Therefore, the binding properties of (-)-[3H]nicotine on rabbit urinary detrusor muscle membrane fractions were studied to evaluate the effects of chronic nicotine treatment on nicotinic receptors. Specific (-)-[3H]nicotine binding reached saturation and Scatchard plots were curvilinear, suggesting the existence of two different affinity sites for (-)-[3H]nicotine. Dissociation constants (KD) and maximum binding sites (Bmax) were KD1 = 4.91 +/- 1.88 nM, Bmax1 = 2.42 +/- 0.22 fmol/mg protein and KD2 = 263 +/- 56 nM, Bmax2 = 25.0 +/- 4.3 fmol/mg protein. In urinary bladder membrane fractions from chronic nicotine-treated rabbits, KD and Bmax values were KD1 = 3.96 +/- 0.38 nM, Bmax1 = 1.07 +/- 0.25 fmol/mg protein and KD2 = 249 +/- 12 nM, Bmax2 = 10.8 +/- 1.5 fmol/mg protein. Dissociation constants for both sites following chronic nicotine treatment did not change but maximum binding site numbers for both sites significantly decreased (p less than 0.05). These results suggest that the decrease in contractile response evoked by nicotine after chronic nicotine treatment in rabbit urinary bladder is due to a decrease in numbers of nicotinic receptors. PMID- 2328449 TI - No rarefaction of cerebral arterioles in hypertensive rats. AB - A reduction in the density of small arterioles (rarefaction) has been reported in several vascular beds of the spontaneously hypertensive rat (SHR). There have been conflicting reports on the existence of rarefaction in the pial vasculature of SHR. In this study, we determined whether there was rarefaction of pial arterioles in several models of hypertension. We studied SHR; two-kidney, one clip Goldblatt hypertensive rats; deoxycorticosterone-salt hypertensive rats; and Dahl salt-sensitive rats fed high salt diet. The two groups of normotensive controls were Wistar--Kyoto rats and Dahl salt-sensitive rats fed low salt diet. The duration of hypertension was about 2 months. Density of first-, second-, third-, and fourth-order arterioles was determined by counting the number of vessels from enlarge photographs. We also measured the lengths of segments of the arterioles. We did not observe any evidence of rarefaction of arterioles in the pial vasculature in any of the hypertensive groups of rats. We conclude that (i) rarefaction of arterioles does not occur in the pial microvasculature after approximately 2 months of hypertension and (ii) rarefaction of pial arterioles does not account for abnormalities in the cerebral circulation of hypertensive rats such as protection of the blood-brain barrier or changes in autoregulation of cerebral blood flow. PMID- 2328450 TI - Transferrin delays oxygen radical induced cardiac-contractile failure. AB - The role of iron-loaded transferrin in xanthine-xanthine oxidase (X-XO) induced cardiac injury in isolated perfused rat hearts was examined. X (2 mM) - XO (10 U/L) perfusion resulted in contractile failure, a rise in resting tension, an increase in lipid peroxidation, and myocardial cell damage. The addition of transferrin (2.4 microM) into the X-XO medium had a protective effect, as indicated by an increase in time to contractile failure, a lesser rise in resting tension, a decrease in MDA values, and lesser damage compared with the X-XO perfused controls. Ultrastructural studies revealed localization of transferrin along the capillary basement membrane. In contrast, addition of transferrin and Desferal (desferrioxamine mesylate, 3 mM, an iron chelator) into X-XO medium caused a rapid contractile failure as well as a rise in resting tension, and in these hearts transferrin was localized inside the myocytes. These findings suggest that a vascular supply of iron protein chelators may have a beneficial effect against myocardial cell injury caused by a vascular source of oxygen radicals. PMID- 2328451 TI - Increased sympathetic innervation in the cerebral and mesenteric arteries of hypertensive rats. AB - The density of catecholamine-containing nerve fibers was studied in the cerebral and mesenteric arteries from normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) in the growing (SHR, WKY) and adult (SHR, SHRSP, WKY) animals. Cerebral arteries from SHR showed an increased adrenergic innervation from day 1. The nerve plexuses reached an adult pattern earlier in SHR than in WKY. The arteries from adult SHR and SHRSP (22 weeks old) showed a markedly higher nerve density than WKY. There was a positive linear correlation between blood pressure and nerve density for four cerebral arteries. The mesenteric arteries were not innervated at birth. However, hyperinnervation of these arteries in the SHR was already present at 10 days of age as compared with WKY. Sympathectomy with anti-nerve growth factor and guanethidine caused a complete disappearance of fluorescent fibers in the mesenteric arteries from SHR and WKY, and in the cerebral arteries of WKY. The same procedure caused only partial denervation of the cerebral arteries from hypertensive animals. We postulate that the increase in nerve density in the cerebral arteries from the hypertensive rats may contribute to the development of arterial hypertrophy in chronic hypertension through the trophic effect of the sympathetic innervation on vascular structure. PMID- 2328452 TI - Effect of furegrelate on renal plasma flow after angiotensin II infusion. AB - We had previously shown that selective thromboxane synthetase inhibition with furegrelate increases urinary excretion of 6-ketoPGF1 alpha, the hydrolysis product of prostacyclin after stimulation of renal prostaglandin synthesis with furosemide. The present study assessed the functional significance of this "redirection" of prostaglandin formation using a more physiologic stimulus, angiotensin II. Sprague-Dawley rats (n = 27) were fitted with a transabdominal bladder cannula. Five days later they were given angiotensin II (10 mg.kg-1.min 1) by intravenous infusion. After 30 min, an infusion of furegrelate, 2 mg/kg, then 2 mg.kg-1.h-1, (n = 9); indomethacin, 2 mg/kg, then 2 mg.kg-1.h-1 (n = 9); or vehicle, 250 microL, then 0.018 mL/min (n = 9) was begun for 60 min. Clearance of [14C]para-aminohippuric acid was taken as a measure of renal plasma flow. Angiotensin II raised the mean arterial pressure in all groups. Administration of furegrelate or indomethacin did not change mean arterial pressure or heart rate. Angiotensin II reduced [14C]p-aminohippuric acid clearance by about 32% (1.42 +/- 0.18 to 0.97 +/- 0.07 mL.min-1.100 g-1, p less than 0.05). Furegrelate attenuated this renal vasoconstriction (0.97 +/- 0.07 to 1.38 +/- 0.17 mL.min-1.100 g-1, p less than 0.05), while indomethacin increased it by a further 32% (1.78 +/- 0.12 to 1.20 +/- 0.12 mL.min-1.100 g-1, p less than 0.05). Vehicle alone had no effect. Furegrelate reduced serum thromboxane B2 by 90% (6.52 +/- 0.030 to 0.7 +/ 0.21 ng/100 microL, p less than 0.05), while indomethacin reduced it by 73% (5.9 +/- 0.99 to 1.4 +/- 0.20 ng/100 microL, p less than 0.05). We conclude that furegrelate attenuates the renal vasoconstriction of angiotensin II, presumably by enhancing the formation of vasodilator prostaglandins. PMID- 2328453 TI - Fluid production by in vitro lungs from fetal guinea pigs. AB - Lungs from fetal guinea pigs (54-67 days of gestation) were supported in vitro, and lung liquid secretion rates were measured by a dye-dilution technique. The average secretion rate in the first hour was 2.14 +/- 0.08 (SE) mL x kg-1 body weight.h-1 (0.21 +/- 0.01 mL/h) (n = 450); this was comparable to intact preparations. In an independent study of 30 lungs, secretion continued unchanged for 3 h, with no significant change in fluid composition. Between 54 days and term, production appeared to fall in terms of millilitres per kilogram per hour. The following agents were placed in the supporting saline during the middle hour of incubation. (i) Sodium iodoacetate: at 10(-4) M this produced a fall in secretion (fall, succeeding hours; 55.4 +/- 23.0 and 64.9 +/- 17.5%; n = 6); at 10(-3) M it stopped secretion (fall, succeeding hours; 87.2 +/- 10.3 and 100%, n = 6). (ii) Ouabain: at 10(-5) M there was no change in production (n = 6); at 10( 4) M, four preparations were unaffected, two reduced production. (iii) Epinephrine (10(-7) M) produced a significant fall in production in all cases (n = 6); in four preparations secretion reduced (average fall, 64.4 +/- 10.8%); in two preparations there was reabsorption (average rate, -1.03 mL.kg-1.h-1). This extends the effect of epinephrine to the guinea pig, and suggests that the in vitro preparation is a useful model for studies of the fetal lung. PMID- 2328454 TI - Absorption of triglycerides in the absence of lipase. AB - Medium chain triglycerides are considered to be readily absorbed intact in the absence of pancreatic lipase, unlike long chain triglycerides. Commercial medium chain triglyceride oils comprise various medium chain fatty acids from 6 to 12 carbons in length resulting in triglyceride molecules of different sizes and molecular weights. The effect of molecular weight and hence fatty acid chain length on the efficiency of intact medium chain triglyceride absorption is unknown. Therefore, this study measured, using a single-pass marker perfusion technique, intestinal jejunum absorption of five medium chain and one long chain triglycerides in anesthetized Sprague-Dawley rats. The molecular weights of the five medium chain triglycerides were 470.7, 498.8, 526.8, 554.9, 639.0, and the long chain triglyceride, 885.4. Residual luminal pancreatic lipase was removed prior to lipid perfusion. This study demonstrated that medium chain triglycerides were absorbed in the absence of lipase whereas long chain triglyceride was not. There was no significant variation in the absorption of the five different medium chain triglycerides perfused. The molecular weight of the medium chain triglyceride did not affect its intact absorption by the small intestine. PMID- 2328455 TI - The influence of renal nerves on electrolyte excretion in conscious and anesthetized rats fed or fasted overnight. AB - The role of the renal nerves in the electrolyte excretion of rats fed or fasted overnight was determined in conscious rats and anesthetized (Inactin) and surgically prepared rats. In conscious rats sodium excretion, as measured in a 1 h urine collection period after feeding or fasting overnight, was decreased with fasting with or without renal nerves. Renal nerve activity, as measured by norepinephrine turnover (inhibition of tyrosine hydroxylase by alpha-methyl-p tyrosine), was not different between conscious fed or fasted rats and increased to the same extent in fed and fasted rats when anesthetized and surgically prepared. Anesthetized, surgically prepared rats infused with 5.0% glucose showed a denervation natriuresis if rats were fed overnight, but not if they had been fasted overnight. Potassium excretion in conscious and anesthetized rats was lower in fasted rats than fed rats with or without renal nerves. These data suggest (i) renal nerves are not involved in the renal response to an overnight fast in conscious rats, and (ii) in anesthetized, surgically prepared rat renal sympathetic tone is enhanced and denervation natriuresis occurs if rats are fed but not if fasted. Potassium excretion is a reflection of whether rats are fed or fasted and not whether they have renal nerves. PMID- 2328456 TI - 8-Bromo-cyclic GMP inhibits the calcium channel current in embryonic chick ventricular myocytes. AB - Superfusion with 8-bromo-cyclic GMP or intracellular injection of cyclic GMP inhibits calcium-dependent slow action potentials in embryonic chick or guinea pig ventricular cells, suggesting that cyclic GMP inhibits calcium currents. Recently, cyclic GMP has been shown to reduce cyclic AMP-stimulated calcium currents in voltage-clamped ventricular myocytes. Since earlier results in intact cells had suggested that cyclic GMP might inhibit basal (i.e., unstimulated by cyclic AMP) calcium currents, we directly investigated the effect of 8-bromo cyclic GMP on basal calcium channel currents (using barium as the charge carrier) in voltage-clamped ventricular myocytes isolated from embryonic chick hearts. Superfusion with 1 mM 8-bromo-cyclic GMP (without prior cyclic AMP elevation) progressively decreased peak calcium channel currents (-68% at 15 min after the onset of drug exposure). In contrast, the currents were unchanged during 15 min superfusion with control solution, or 1 mM 8-bromo-GMP (the noncyclic inactive analog of 8-bromo-cyclic GMP). The present results in voltage-clamped embryonic chick heart cells indicate that cyclic GMP can inhibit basal calcium channel currents, apparently through a cyclic AMP-independent mechanism. PMID- 2328457 TI - Potassium currents in rat cortical neurons in culture are enhanced by the antiepileptic drug carbamazepine. AB - We report that carbamazepine (Tegretol), a drug that is useful for the treatment of complex partial seizures, enhances outward, voltage-dependent K+ currents generated by rat neocortical cells in culture and recorded with patch-clamping techniques. This effect is seen in the presence of therapeutic concentrations of carbamazepine (10-20 microM). Furthermore, at these doses carbamazepine does not influence voltage-dependent inward Na+ and Ca2+ currents recorded in these cells. The action exerted by carbamazepine on K+ currents is a novel finding and might represent an important mechanism for controlling neocortical excitability and thus the generation of epileptiform activity. PMID- 2328458 TI - Keeping ahead of the media. PMID- 2328459 TI - Cigarette in CMAJ ad. PMID- 2328460 TI - Why are Canada's nurses quitting? PMID- 2328461 TI - Medical journals and the 6 o'clock news. PMID- 2328462 TI - Patient choice and medical treatment. PMID- 2328463 TI - Making hockey safer. PMID- 2328464 TI - Resuscitation of the terminally ill. PMID- 2328465 TI - Placebos: some ethical considerations. PMID- 2328466 TI - Physician's view of the GST (goods and services tax) PMID- 2328467 TI - Interest in alternative birthplaces among women in Ottawa-Carleton. AB - Birthing rooms, birth centres and home birth have been proposed as alternatives to the traditional in-hospital caserooms to meet the needs of women and their families more effectively. We performed a descriptive survey to determine the level of interest of childbearing women in the Ottawa-Carleton region in these birthplaces and to examine the characteristics of women who express an interest in using them. Of the 1629 women who gave birth between July 1 and Aug. 28, 1987, 1115 (68.4%) completed a self-administered questionnaire during the pregnancy, in the early postpartum period in hospital or at home. Of the respondents 577 (53.1%) said they would choose the caseroom, 316 (29.1%) the birthing room, 165 (15.2%) the birth centre and 30 (2.8%) home birth. The women who expressed an interest in a birthplace other than the caseroom were more likely than the others to be older, married, well-educated and interested in midwifery services and to breastfeed their babies (p less than 0.05). They were also more likely to have had a low-intervention vaginal birth (p less than 0.05). The interest expressed in birthing rooms, birth centres and home birth suggests that these alternatives should be considered for inclusion in the health care system. PMID- 2328468 TI - Dimenhydrinate dependence and withdrawal. PMID- 2328469 TI - If CMPA (Canadian Medical Protection Association) changed its policy there would be fewer lawsuits, lawyer maintains. PMID- 2328470 TI - Both scientists and laymen in fight to defend animal-based research. PMID- 2328471 TI - Guidelines covering disclosure of errors now in place at Montreal hospital. PMID- 2328472 TI - A time to die. PMID- 2328473 TI - Do West German medical schools provide a lesson for Canada? PMID- 2328474 TI - The American Society Workshop on the Management of Limited Breast Cancer. Introduction. PMID- 2328475 TI - The American Cancer Society Workshop on Management of Limited Breast Cancer. Naples, Florida, September 11-12, 1989. PMID- 2328476 TI - Adjuvant systemic therapy. PMID- 2328477 TI - Radiation oncology. PMID- 2328478 TI - Pathologic findings from the National Surgical Adjuvant Breast and Bowel Projects (NSABP). Prognostic discriminants for 8-year survival for node-negative invasive breast cancer patients. AB - Twenty-two pathologic features (including estrogen and progesterone receptors) and four clinical features observed in 950 women with node-negative Stage I invasive breast cancer who enrolled in the National Surgical Adjuvant Breast and Bowel Projects (NSABP) protocol B-06 were evaluated for their possible prognostic significance. Preliminary univariate analysis revealed ten characteristics that were significant in this regard at the 1% level. Their assessment in a Cox regression model demonstrated only three to be prognostically important; notable among these were nuclear grade, histologic tumor type, and race. Life-table plots revealed that 86% of patients whose cancers exhibited good nuclear grade survived for 8 years as opposed to 64% in whom the nuclear grade was scored as poor. Analyses demonstrated three prognostic categories for histologic tumor type. Patients with either mucinous, tubular, or papillary cancers fared significantly better than those having not otherwise specific (NOS) or atypical medullary tumors. Survival for those with typical medullary, NOS combinations, or lobular invasive cancers was intermediate. Blacks fared worse than whites. Survival was correspondingly better or worse when two favorable or unfavorable characteristics were detected. The number of black women in this cohort was considered too small for further subset analysis although generally the pattern of findings suggested that survival was worse for blacks than for whites in all subsets. A review, as well as our own experience, suggested that nuclear grade is as good if not better as a predictor of survival in node negative patients as information derived from DNA analyses, immunohistochemical demonstration of erb-B2 overexpression, and, possibly, the tumor labeling index at predicting survival in node-negative patients. PMID- 2328479 TI - Progress in early breast cancer detection. AB - Evidence indicates progress in the early detection of breast cancer. After 1982 there was a reported increase in the incidence of breast cancer, presumably as a result of increased screening for the disease. The increase was especially noted in early stage breast cancer. The incidence of in situ cases also increased. Since 1973 the San Francisco-Oakland Bay area has reported a statistically significant decrease in mortality for white women. The evidence supports continued efforts at early breast cancer detection. PMID- 2328480 TI - Effects of the pineal hormone melatonin on the anchorage-independent growth of human breast cancer cells (MCF-7) in a clonogenic culture system. AB - Only physiological levels of melatonin exert an antiproliferative effect on MCF-7 breast cancer cells grown in an anchorage-dependent culture system. We investigated melatonin's effect on the anchorage-independent growth of MCF-7 cells as well as the dose-response characteristics of this indoleamine under clonogenic culture conditions. Melatonin's inhibitory effect, with respect to the number and size of colonies formed, exhibit a linear dose-response curve with pharmacological concentrations producing a maximal inhibition while subphysiological levels of melatonin induce minimal inhibition. These results indicate that cellular attachment may modify the sensitivity of MCF-7 cells towards melatonin. PMID- 2328481 TI - The effect of prolonged incubations and heat denaturation on melphalan-induced DNA cross-links as measured by the ethidium bromide fluorescence assay. AB - Th ethidium bromide fluorescence assay detects DNA interstrand crosslinks following heat denaturation of DNA on the basis of a 20-25 fold enhancement of ethidium bromide fluorescence in the presence of double stranded DNA. This assay has been utilized to detect DNA cross-links produced by melphalan in lymphocytes from chronic lymphocytic leukemia patients. The percentage of DNA cross-links (C) in these cells did not vary linearly with the concentration of melphalan, possibly as a result of DNA fragmentation during a 16 h lysis to degrade RNA. In order to investigate this, DNA was exposed to melphalan and then the Ct was determined immediately after maximal DNA cross-link formation or after a 16 h incubation. The additional incubation period did not alter the linear relationship between Ct and melphalan concentration. Further, the DNA cross-links produced by melphalan does not appear to be heat labile since varying the heat denaturation period from 5 to 15 min had no effect on Ct. These results suggest that this assay can accurately quantitate the percentage of DNA cross-links produced by melphalan and that the curvilinear relationship between Ct and melphalan concentration in malignant human lymphocytes is not due to the ethidium bromide fluorescence assay. PMID- 2328482 TI - Biological response of the anti-estrogen ICI 164,384 in human hormone-dependent and hormone-independent mammary cancer cell lines. AB - The biological response on proliferation and progesterone receptor (PR) of the anti-estrogen ICI 164,384 [N-n-butyl-N-methyl-11-(3,17 beta-dihydroxyestra 1,3,5(10-trien-7 alpha-yl))-undecanamide] was studied in different mammary cancer cell lines. In the hormone-dependent cancer cell lines (MCF-7 and T-47D) this anti-estrogen significantly decreased cell proliferation, but to reduce 50% of the growth in the MCF-7 cells a very low concentration (10(-9) M) is necessary. Similar effects in the T-47D cell are obtained with a dose of 100-1000 times (10( 6)-10(-7) M). The stimulatory effect in cell proliferation induced by estradiol is also inhibited by ICI 164,384 in both cell lines. This anti-estrogen has no effect on proliferation in the anti-estrogen resistant cell line LY-2, or in the hormone-independent cell line MDA-MB-436. Studies on thymidine incorporation correlate with the effect on cell proliferation. ICI 164,384 also blocks the stimulatory effect on progesterone receptor provoked by estradiol in MCF-7 cells and in T-47D cells which contain high concentration levels of progesterone receptor ICI 164,384 significantly decreases the PR concentrations in both the non-treated and estradiol-treated cells. It is concluded that ICI 164,384 is a full antagonist in the hormone-dependent breast cancer cells, but it has no effect in the anti-estrogen-resistant or in hormone-independent cell lines. PMID- 2328483 TI - Inhibitory effects of novel festuclavine derivatives on nucleoside uptake and incorporation into DNA and RNA in human lymphoid leukemia Molt 4B cells. AB - Effects of festuclavine derivatives on nucleoside uptake by human lymphoid leukemia Molt 4B cells and on incorporation into TCA-insoluble materials in the cells were examined. The uptake and incorporation of uridine or thymidine were suppressed by festuclavine (EN01), 13-bromo-1-cyclopropylmethyl-festuclavine (EN02), 1-(4-chloro-benzenesulfonyl)festuclavine (EN03) and 1-cyclopentyl festuclavine (EN04) at 10-50 microM. Among these compounds, EN02 was most effective and at 50 microM it completely suppressed cellular uptake of the nucleosides and their incorporation into TCA-insoluble materials inhibiting the cellular proliferation. EN03 and EN04 moderately inhibited the transport and incorporation of the nucleosides in dose-dependent manners, while the mother compound EN01 had the least inhibitory effect. These findings indicated that alkylation at the indole nitrogen in combination with bromination at C-13 of the festuclavine molecule strengthened its inhibitory action on nucleoside uptake to a remarkable extent. The inhibition curves of nucleoside incorporation into TCA insoluble materials showed quite similar dose-dependence to those of the inhibition curves for cellular nucleoside transport. These results suggest that the inhibitions of DNA and RNA syntheses by the festuclavine derivatives are due to the depressed transport of nucleosides into the leukemia cells. PMID- 2328484 TI - Species differences in sodium o-phenylphenate induction of urinary bladder lesions. AB - The effects of sodium o-phenylphenate (Na-OPP) treatment on urinary bladder epithelium were examined in male F344 rats, B6C3F1 mice, Syrian golden hamsters and Hartley guinea pigs. Na-OPP was incorporated into diet at a dose of 2% and administered for 4, 8, 12, 24, 36 or 48 weeks. Simple and papillary or nodular (PN) hyperplasias were evident on light microscopy and pleomorphic microvilli demonstrated by scanning electron microscopy were only observed in rats, the lesions becoming more advanced with continued chemical feeding. In mice, hamsters and guinea pigs, proliferative lesions relating to Na-OPP administration were not observed. No significant differences in urinary pH, osmolality or crystal formation were apparent between the various animal species. Since carcinogenicity has been demonstrated for Na-OPP in rats but not in mice, the present findings suggest that Na-OPP might not exert urinary bladder carcinogenic potential in hamsters and guinea pigs. PMID- 2328485 TI - Life-style, workplace, and stomach cancer by subsite in young men of Los Angeles County. AB - A case-control study involving interviews with 137 incident male cases of stomach cancer under the age of 55 yr and an equal number of age- (within 5 yr), race-, and sex-matched neighborhood controls in Los Angeles County was conducted. Cases were more likely to be foreign born and had less education compared with controls. Any use of tobacco products conferred a 2-fold increase risk for stomach cancer; the effect was present in all subsites: the cardia; fundus/body; and antrum/pylorus. Weekly use of alcoholic beverages was also a risk factor, but the effect was not observed in the antrum/pylorus. In comparison with controls, cases had a significantly higher intake of beef (cardia only) and barbecued/smoked foods, had a lower intake of fresh fruits/vegetables, and were more likely to prefer white than whole grain bread. Occupational exposure to metal dust was associated with a 70% increased risk of stomach cancer, with an increase in risk as the duration of exposure increased. This association was most pronounced for tumors in the antrum and pylorus. Subjects with a history of stomach or duodenal ulcer showed a 2-fold increased risk of stomach cancer. The effects of smoking, alcohol, intake of white bread, history of ulcer, and exposure to metal dust remained statistically significant when these variables were examined simultaneously in multivariate analyses and when the multivariate analyses were confined to directly interviewed subjects. PMID- 2328486 TI - Gestational and familial risk factors for childhood astrocytoma: results of a case-control study. AB - Gestational and familial risk factors were investigated for their association with astrocytoma, the most frequently occurring brain tumor in children. A case control study of 163 matched pairs was performed. Cases under 15 years of age at diagnosis in 1980-1986 were identified through the tumor registries of 8 hospitals in Pennsylvania, New Jersey, and Delaware. Controls were selected by random digit dialing and were matched to cases for age, race, and telephone area code and exchange. Maternal antinausea medications increased the risk of childhood astrocytoma [OR (odds ratio) = 2.0, P = 0.04]. Cured meat consumption during pregnancy was more common among cases (OR = 1.9, P = 0.07), and a significant trend with increasing frequency of consumption was observed (P = 0.04). Results for gestational exposure to marijuana (OR = 2.8, P = 0.07) were of borderline significance. Gestational exposure to neurally active medications, alcohol, and tobacco were not risk factors. There was a significant trend for cases to be of higher birth weight (P = 0.03). Mental retardation (OR = 3.0, P = 0.04) and cancer (OR = 1.7, P = 0.02) in a relative of the child significantly increased the risk of astrocytoma. Significantly increased risks were observed for brain tumors in relatives of children 0-4 years of age at diagnosis (OR = 6/0, P = 0.04). A significant protective effect was observed for maternal history of miscarriage or stillbirth (OR = 0.5, P = 0.01). The results of this study suggest that some gestational and familial factors may increase the risk of childhood astrocytoma. PMID- 2328487 TI - Effects of indole-3-carbinol on lung tumorigenesis and DNA methylation induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and on the metabolism and disposition of NNK in A/J mice. AB - The effects of indole-3-carbinol (I3C) on lung neoplasia induced by the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were assessed in an A/J mouse pulmonary adenoma bioassay. Mice were administered corn oil or I3C (25 or 125 mumol/mouse/day) by gavage for 4 consecutive days. Two h after the final pretreatment, mice were administered a single dose of NNK (10 mumol/mouse) i.p. Pulmonary adenomas were quantitated 16 wk after NNK dosing. Mice pretreated with corn oil developed 10.7 tumors/mouse; I3C pretreatment at either dose level inhibited tumor multiplicity by approximately 40%. The effects of I3C on NNK-induced DNA methylation in the lungs and livers of A/J mice were assessed using the same dosing regimen as in the bioassay. Both dose levels of I3C inhibited pulmonary O6-methylguanine formation by at least 50%, but enhanced hepatic DNA methylation at 2 or at 6 h after NNK administration. The effects of I3C pretreatment on NNK metabolism were also investigated. Hepatic microsomes of I3C-pretreated mice showed increased formation of alpha-hydroxylation products, while no significant effect of I3C pretreatment was observed in pulmonary microsomes. The effects of I3C on [5-3H]NNK disposition were also evaluated. I3C pretreatment produced lower levels of total radioactivity in the lung when compared with controls. Additionally, lower proportions of NNK and its carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were found in the lungs of I3C-pretreated mice. These results demonstrate that I3C inhibits NNK-induced lung neoplasia in A/J mice and suggest that the basis of this inhibition is the decrease in O6-methylguanine formation in A/J lung caused by I3C pretreatment. This decrease in lung DNA methylation appears to be due to the decreased bioavailability of NNK and 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanol in the lungs of I3C-treated mice which, in turn, may be a result of increased metabolic alpha-hydroxylation of NNK by the liver. PMID- 2328488 TI - Chemotherapeutic characterization in mice of 2-amino-9-beta-D-ribofuranosylpurine 6-sulfinamide (sulfinosine), a novel purine nucleoside with unique antitumor properties. AB - In preclinical investigations performed in mice, 2-amino-9-beta-D-ribofuranosyl purine-6-sulfinamide (sulfinosine), a novel derivative of 6-thioguanosine (6TGR), was active against six solid tumors and four strains of experimental leukemia. Sulfinosine penetrated the central nervous system more readily than did 6TGR and, when given repeatedly, was much more effective in the treatment of L1210 leukemia, being curative for some mice. Other findings of major interest to us were the different dosing characteristics of sulfinosine and 6TGR, the divergent efficiencies of the two drugs in generating cellular resistance, and the activity of sulfinosine against experimental leukemias refractory to 6TGR and other experimental or clinically used chemotherapeutic agents. The chemotherapeutic characterization of sulfinosine that evolved from these studies suggests that this agent may have unique properties that deserve clinical consideration. Both the dosing characteristics of the drug and its pronounced activity against thiopurine-resistant experimental leukemia favor the possibility that sulfinosine could be used to advantage in the treatment of human leukemia unresponsive to 6 mercaptopurine or 6-thioguanine. PMID- 2328489 TI - Ultraviolet radiation induction of ornithine decarboxylase in rat keratinocytes. AB - UV radiation plays an important role in the induction of cutaneous malignancy, including basal cell and squamous cell carcinomas and malignant melanoma. In addition to its effects on DNA damage and repair mechanisms, UV radiation has been shown to modulate the expression of specific genes, altering the levels of their mRNAs and the synthesis of their corresponding proteins. In order to gain further information about the molecular effects of UV radiation, we have studied the regulation of ornithine decarboxylase (ODC) gene expression in response to UVB radiation. ODC is the rate-limiting enzyme in polyamine biosynthesis, is involved in growth and differentiation, and has been implicated in carcinogenesis. Keratinocytes grown in culture were either sham-irradiated or exposed to increasing doses of UVB (1-5 mJ/cm2). Northern blot analysis of keratinocyte RNA under basal conditions demonstrated the presence of two ODC mRNA transcripts. Increasing exposure to UVB resulted in a dose-dependent increase in the levels of both ODC mRNA transcripts. The induction of ODC gene expression following UVB was noted 2 h after UVB exposure, and ODC mRNA levels continued to increase up to 24 h after UVB exposure. The UVB-induced increase in ODC gene expression was not serum dependent, despite the ability of serum alone to induce ODC gene expression. The mRNA transcripts for actin and hexosaminidase A were not induced after UVB exposure. These studies show that the UVB-induced increase in ODC activity is due, at least in part, to an increase in ODC gene expression and they provide a useful model for the analysis of the molecular effects of UVB radiation. PMID- 2328490 TI - Labeling index and labeling distribution of cells in esophageal epithelium of individuals at increased risk for esophageal cancer in Huixian, China. AB - The pattern of proliferation of epithelial cells in esophageal epithelium was studied by means of [3H]deoxythymidine labeling of esophageal epithelium in subjects from Huixian, Henan Province, China, a high-risk geographical region for esophageal cancer. Comparisons were made among patterns of cell proliferation observed in normal esophagus, in hyperplasia, in mild dysplasia, and in moderate dysplasia in a total of 118 subjects. The amount of cell proliferation observed was lowest in normal esophageal epithelium and increased progressively in subjects having hyperplasia, mild dysplasia, and moderate dysplasia. The location of proliferating cells was limited mainly to the base of the esophageal epithelium in normal esophagus, but expanded toward the surface of the esophageal lining in individuals with hyperplasia and dysplasia. The larger total numbers of proliferating cells in the esophageal epithelium and the progressive expansion of the proliferative compartment toward the epithelial surface found in hyperplasia and in dysplasia could both facilitate the screening of subjects for esophageal cancer risk and serve as intermediate biomarkers in prophylactic dietary or pharmacological intervention studies. PMID- 2328491 TI - Effects of 1-beta-D-arabinofuranosylcytosine on DNA replication intermediates monitored by pH-step alkaline elution. AB - The pH-step alkaline elution method enables the isolation and quantification of nascent DNA (nDNA) replication intermediates, including Okazaki fragments, short length nDNA from replicon origins, longer lengths of nascent but subgenomic length nDNA (molecular weight, 20-30 x 10(6)), and full (or genomic) length nDNA (L. C. Erickson et al., Chromosoma, 74: 125-139, 1979). We utilized this technique to study, in HL-60 cells, the effects of 1-beta-D arabinofuranosylcytosine (ara-C) on the formation of these replication intermediates and the kinetics of transit of radiolabel from [3H]thymidine ([3H]dThd) or [3H]-ara-C through these nDNA fragments and into full length nDNA. In the continuous presence of [3H]-ara-C (4 microM), the majority of radiolabel (greater than 85%) remained in the nascent subgenomic fractions, with 30-50% remaining in Okazaki fragments. These proportions did not change substantially with increasing time of exposure to [3H]-ara-C (from 1 to 24 h), although the total amount of [3H]-ara-C incorporated into DNA continued to increase with increasing time of exposure. In contrast, when cells were exposed to [3H]-ara-C for 1 h, placed in drug-free medium, and studied by the pH-step method at various times thereafter, the transit of radiolabel through progressively larger nDNA intermediates and into full length nDNA was rapid and equal to that of [3H]dThd in cells not exposed to drug. The observed elution of [3H]-ara-C in the subgenomic-length DNA fragments was not due to ara-C-induced breaks in template (parental) DNA and subsequent incorporation of [3H]-ara-C into the template strand, since ara-C treatment of cells prelabeled with [14C]dThd failed to cause substantial elution of the 14C label at the various pH steps used. In studies of the effects of ara-C on [3H]dThd incorporation into nDNA, concentrations of 1 to 10 microM ara-C inhibited total incorporation of radiolabel into DNA by greater than 90% and incorporation into full length nDNA by greater than 97%. In contrast, these concentrations of ara-C failed to decrease the amount of [3H]dThd incorporated into Okazaki fragments or other non-mitochondrial low molecular weight nDNA, compared to control. These studies demonstrate that, in HL-60 cells, ara-C causes profound inhibition of nascent chain elongation, does not cause chain termination, and does not inhibit initiation. In fact, ara-C may stimulate initiation, leading credence to recent theories proposing endoreduplication or reinitiation as consequences of ara-C incorporation into DNA. PMID- 2328492 TI - Phase I trial of 5-fluorouracil and dipyridamole administered by seventy-two-hour concurrent continuous infusion. AB - Forty-seven patients with advanced malignancies were treated with a concurrent 72 h continuous infusion of 5-fluorouracil (FUra) and dipyridamole. The FUra dose was escalated over the dose range of 185 to 3600 mg/m2/day for 3 days. Dipyridamole was administered in a fixed dose of 7.7 mg/kg/day for 3 days. A total of 155 courses of therapy were completed of which there were 31 paired courses of the combination and FUra alone, at the same dose of FUra and in the same patient. This was for purposes of analysis of pharmacokinetics and modulation of FUra toxicity by dipyridamole. Stomatitis was the dose-limiting toxicity experienced by patients entered into this trial. Myelosuppression was not a serious problem. Increasing FUra plasma concentration was associated with greater leukopenia and stomatitis. Dipyridamole did not appear to modulate the systemic toxicity of FUra. The pharmacokinetics of FUra were altered by the concurrent administration of dipyridamole. Dipyridamole promoted the total body clearance of FUra which resulted in lower mean steady-state FUra plasma concentrations when compared with courses of FUra alone administered at the same dose level. These differences were statistically significant over the course of the trial. For courses of the combination, FUra exhibited linear pharmacokinetics over the dose range studied. Total body clearance of FUra declined slightly at the higher dose levels, but the differences were not significant. For courses of FUra alone, total body clearance was significantly decreased above the dose level of 2300 mg/m2/day. At the maximal tolerated dose of FUra, 2300 mg/m2/day x3, mean steady-state FUra plasma concentration and total body clearance were 6.6 microM and 122 liters/h/m2, respectively, for courses of the combination. The corresponding pharmacokinetic parameters were 7.4 microM and 103 liters/h/m2 for courses when FUra was given alone. Further evaluation of the utility of this regimen and basis of these pharmacokinetic observations appear warranted. PMID- 2328493 TI - Effects of neonatal and adult castration and of testosterone substitution in male rats on growth of enzyme-altered hepatic foci in the resistant hepatocyte model. AB - Marked sex differences in the growth of enzyme-altered hepatic foci have been observed in rats treated according to the "resistant hepatocyte model." The present study was performed to investigate the effect of neonatal and adult castration of male rats, with or without testosterone substitution, on the growth rate of foci during selection of initiated cells with 2-acetylaminofluorene and partial hepatectomy. Neonatal castration of male rats decreased focal growth to the same level as in female rats. Castration of adult male rats 2 wk before initiation with diethylnitrosamine also decreased the growth rate of foci, but less markedly than in neonatally castrated rats. Testosterone substitution of male rats castrated as neonates or as adults, from 10 days after initiation with diethylnitrosamine, restored focal growth to that of sham-castrated controls. Previous investigations concerning the role of gonadal hormones in sex differentiation of various liver functions indicated a role of the hypothalamo pituitary-liver axis in mediating the effects of androgens. It is therefore also suggested that the effects of androgens on early steps of hepatocarcinogenesis observed in the present study are mediated by similar mechanisms, possibly through an influence on the metabolism of 2-acetylaminofluorene. PMID- 2328494 TI - Pharmacokinetic and toxicity scaling of the antitumor agents amsacrine and CI 921, a new analogue, in mice, rats, rabbits, dogs, and humans. AB - The aim was to investigate interspecies relationships between body weight (W) (kg) and various pharmacokinetic parameters for the anti-tumor agents amsacrine and its 4-methyl-5-(N-methylcarboxamide) analogue, CI-921, and examine which pharmacokinetic parameter, if any, might be used to predict the toxicity of these agents. Pharmacokinetic, plasma protein binding, and toxicity data were available for CI-921 in mice, rats, rabbits, dogs, and humans. For amsacrine, similar interspecies pharmacokinetic data were available but toxicity and protein-binding data were available for only 3 species. Significant linear relationships were obtained for CI-921 between log W and log Vss (liters) (r = 0.971, P = 0.006), and log W and log Cl (liters/h) (r = 0.911, P = 0.031) resulting in the allometric equations Vss = 1.22W0.68 and Cl = 0.91W0.51. For amsacrine these corresponding equations were Vss = 3.37W0.81 (r = 0.996, P less than 0.001), and Cl = 2.28W0.46 (r = 0.952, P = 0.012). When interspecies differences in plasma protein binding were taken into account, the allometric relationships improved and the exponents of the power equations increased. For CI-921 the allometric equations for the kinetic parameters calculated from plasma "free" concentrations were: Vssfu (liters) = 247W0.93 (r = 0.984, P = 0.002) and Clu (liters/h) = 186W0.76 (r = 0.961, P = 0.009). The dog was a noticeable outlier in the relationship between the log maximum tolerated dose (MTD) (mg/kg) of CI-921 and log W. Omission of the latter resulted in a highly significant allometric relationship, MTD = 23.6W-0.14 (r = -0.988, P = 0.012). For amsacrine there was no significant allometric relationship between MTD and W. CI-921s prolonged t1/2 in the dog and the dog's increased susceptibility to CI-921 toxicity suggested a relationship between MTD and t1/2 (h). A significant linear relationship was observed between in MTD and t1/2 (r = -0.994, P less than 0.001), from which the following equation was developed MTD = 47.5e-0.51t1/2 Combining the amsacrine toxicity data in the latter relationship yielded a similar equation MTD = 44.7e 0.51t1/2 (r = -0.933, P less than 0.0001). It was concluded that allometric equations may be developed for CI-921 and amsacrine from animal pharmacokinetic data which allow a reasonable prediction of Cl and Vss in patients, despite these agents being eliminated mainly by biotransformation. However, similar relationships between toxicity and body weight were susceptible to variation between individual species. Species differences in the toxicity of these agents were predictable from the t1/2. This study emphasized the importance of pharmacokinetic data in preclinical toxicity and efficacy testing of antitumor agents. PMID- 2328495 TI - Chromosome abnormalities in malignant lymphoma in patients from Kurashiki: histological and immunophenotypic correlations. AB - Clonal chromosomal abnormalities were found in tumor tissue of 43 (84%) of 51 patients with non-Hodgkin's lymphoma (B-cell, 32; T-cell, 15) from an adult T cell leukemia/lymphoma-nonendemic area in western mainland Japan. Four tumors were tetraploid, and the other 39 had a chromosome number in the diploid range. Trisomies 3, 5, 7, 18, and X, monosomy 13, and loss of an X in female and a Y in male were found in more than three patients each. Structural abnormalities in arms 1p, 1q, 2q, 3q, 13q, 14q, and 18q were found in eight or more patients each. Clustering of breaks occurred in 3q25-29 (ten patients, nine of whom with a B cell tumor), 11q13 (five patients), dir dup(12)(q13-15----q21-24) (four patients), 14q32 (12 patients), and 18q21 (seven patients). The 14q32 translocations were all associated with B-cell tumors. t(8;14) was seen in a small noncleaved cell lymphoma, t(11;14)(q13;q32) in one follicular and three intermediately differentiated lymphocytic lymphomas, and t(14;18)(q32;q21) in two follicular lymphomas and one diffuse small cleaved cell tumor. The translocation partner of 14q could not be determined in the other four patients, three of whom had der(18)t(18;?)(q21;?). The seven 18q21 abnormalities, including a novel translocation t(2;18)(p11;q21.3), all occurred in B-cell tumors; even in the absence of t(14;18), they were closely associated with lymphomas of follicular center cell origin (six of seven). PMID- 2328496 TI - Mechanism of epipodophyllotoxin-induced cell death in poly(adenosine diphosphate ribose) synthesis-deficient V79 Chinese hamster cell lines. AB - Mutant Chinese hamster V79 cells selected for alterations in poly(ADP-ribose) metabolism were shown to be resistant to epipodophyllotoxin (VP-16)-induced cytotoxicity. Cell lines ADPRT 54 and ADPRT 351 have reduced activity of poly(ADP ribose) polymerase. N2, N3, and N4 cell lines grow in the absence of nicotinamide, with total NAD levels 1.5-3% of those found in parental V79 cells grown in complete medium. When grown in complete medium, the mutant cell lines are 2.3- to 9.6-fold resistant to VP-16-induced cytotoxicity. All of the cell lines respond to VP-16 treatment by formation of protein-cross-linked DNA strand breaks. Upon drug removal, all the cell lines reverse the DNA strand breaks at similar rates. Our studies show a clear dissociation between induction of DNA strand breaks and cytotoxicity. However, there is a good correlation between drug induced sister chromatid exchanges and cytotoxicity. Thus, N3 cells, with low levels of VP-16-induced sister chromatid exchanges, show reduced levels of cytotoxicity relative to parental V79 cells, despite the fact that both cell lines show similar levels of VP-16-induced protein-cross-linked DNA strand breaks. Additional studies show that the time course of VP-16-induced cytotoxicity correlated better with the time course of sister chromatid exchange formation than with protein-cross-linked DNA strand break formation. These studies provide strong support for the proposal that VP-16-induced cytotoxicity involves the induction of sister chromatid exchanges. Thus, we suggest that drug induced stabilization of topoisomerase II-DNA complexes stimulates induction of sister chromatid exchanges, which consequently lead to cell death. PMID- 2328497 TI - Effect of hypoxia on 1,3-bis(2-chloroethyl)-1-nitrosourea cytotoxicity in 9L cells. AB - The cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on 9L rat brain tumor cells were studied under oxic and hypoxic conditions. Acute hypoxia was produced by gassing exponentially growing monolayer cells with 95% nitrogen/5% CO2 for 2 h, after which cells were treated with graded concentrations of BCNU for 1 h. Cell survival was assayed with a colony forming efficiency assay and the extent of DNA cross-linking was measured with the alkaline elution assay. BCNU was more cytotoxic to hypoxic than to oxic cells. There were far more interstrand cross-links formed in hypoxic than in oxic cells, and the number of cross-links could be measured readily in hypoxic cells at very low concentrations of BCNU. This allowed cell survival and cross-linking to be compared at the same dose levels, a correlation not possible for oxic cells in which cross-links are not measurable at low doses. The total intracellular levels of glutathione were lower in hypoxic cells, but the reduced glutathione levels may not be related to the enhanced cell kill because survival of oxic cells treated with BCNU was not affected when cells were depleted of glutathione with buthionine sulfoximine. These results indicate that the additional cell kill produced in 9L cells under hypoxic conditions is related to increased cross-link formation. PMID- 2328498 TI - Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas. AB - Recently, tumor-specific allele loss has been shown to be an important characteristic of some tumors. When such loss includes one or more growth regulatory genes, it may allow the expression of tumorigenicity. Using Southern blots, we analyzed normal and tumor DNA samples from 19 ovarian cancer patients, using a series of polymorphic DNA probes that map to a variety of chromosomal loci. Of 14 informative cases, tumor-specific allelic loss was observed in nine (64%) at the estrogen receptor (ESR) gene locus on chromosome 6q. On chromosome 17p at the D17S28 and D17S30 loci, allelic losses were also detected in 6 of 8 (75%) and 9 of 14 (64%) cases, respectively. Allelic loss at the HRAS1 gene locus on chromosome 11p occurred in 5 of 11 (46%) informative cases. The relatively high incidence of these allelic losses observed on chromosome 6q represents the first implication by molecular genetic analysis of this chromosomal region in a human malignancy, and it thus appears to be a genetic change specific to ovarian carcinoma. DNA sequence losses on 11p and 17p, also reported for other cancers, may reflect the presence of tumor- or growth-suppressor genes on these chromosomes that are important in the genesis of many tumor types, including ovarian malignancies. PMID- 2328499 TI - Androgen-dependent renal microsomal cytochrome P-450 responsible for N hydroxylation and mutagenic activation of 3-methoxy-4-aminoazobenzene in the BALB/c mouse. AB - A murine renal microsomal enzyme responsible for the mutagenic activation of 3 methoxy-4-aminoazobenzene (3-MeO-AAB) was characterized by its catalytic activity for the mutagenic and metabolic conversion of 3-MeO-AAB. Incubation of 3-MeO-AAB with a renal or hepatic microsome fraction from male BALB/c mice in the presence of NADPH and NADH yielded N-hydroxy and 4'-hydroxy metabolites of 3-MeO-AAB as determined by two-dimensional thin layer chromatography, and the enzyme responsible for the N-hydroxylation was named 3-MeO-AAB N-hydroxylase. A mutagenicity test using Salmonella typhimurium TA98 bacteria as a tester strain has revealed that N-hydroxy-3-MeO-AAB is a potent direct mutagen but that 4' hydroxy-3-MeO-AAB is not mutagenic. Although 3-MeO-AAB N-hydroxylase activity in liver microsomes showed no sex difference, the enzyme activity in the kidney was detected from male mice but not from females. However, administration of testosterone to female mice induced the enzyme in the kidney. Castration of male mice depressed the activity of 3-MeO-AAB N-hydroxylase in renal microsomes but it little affected the hepatic activity, and on administration of testosterone to the castrated mice the depressed renal microsomal activity recovered to a normal level. The activity of 3-MeO-AAB hydroxylase and the amount of cytochrome P-450 in renal microsomes showed a close correlation. Both renal and hepatic microsomes required NADPH as a main cofactor to mutagenize 3-MeO-AAB and to yield N-hydroxy 3-MeO-AAB from 3-MeO-AAB, and the enzyme activity was strongly inhibited by 7,8 benzoflavone. When the activities of renal and hepatic 3-MeO-AAB N-hydroxylase were compared on the basis of the amount of cytochrome P-450, the renal type enzyme showed about 8 times greater activity than hepatic type enzyme. These results indicate that the kidney contains an androgen-dependent microsomal 3-MeO AAB hydroxylase which is different from an isozyme present in the liver and which is a new type of cytochrome P-450 isozyme. PMID- 2328500 TI - Leukemia following chemotherapy for breast cancer. AB - Leukemia following chemotherapy for breast cancer was studied among patients diagnosed during 1973-1985 within the population-based tumor registries in the Surveillance, Epidemiology, and End Results Program. Among 13,734 women given initial chemotherapy, 24 developed acute nonlymphocytic leukemia (ANLL) compared to 2.1 expected based on general population rates (observed/expected = 11.5; 95% confidence interval = 7.4-17.1). Overall, 58 excess ANLL occurred per 100,000 women-years at risk for patients treated with chemotherapy. The cumulative incidence was 0.7% at 10 years. Risk remained high over all periods of observation up to 9 years after treatment. Among 7974 women treated only with surgery during 1973 and 1974, a period before the widespread use of adjuvant chemotherapy for breast cancer, ANLL was not significantly increased (observed = 7, expected = 5.1). A case-control study was then conducted in Connecticut to evaluate in more detail the risk associated with adjuvant chemotherapy in the general population. Among 20 cases (17 incident leukemias and 3 deaths due to preleukemia) and 60 matched controls, alkylating agents were linked to an 11.9 fold risk of ANLL and preleukemia (95% confidence interval = 2.6-55). Chemotherapy regimens including melphalan were related to a higher risk of leukemic conditions than those including cyclophosphamide. These data suggest that women in the general population treated with adjuvant chemotherapy for breast cancer are at an increased risk of leukemia, that the risk remains high among long-term survivors, and that risk differs by type of alkylating agent administered. PMID- 2328501 TI - Selectivity of rat and human glutathione S-transferases in activation of ethylene dibromide by glutathione conjugation and DNA binding and induction of unscheduled DNA synthesis in human hepatocytes. AB - The major DNA adduct formed by the carcinogen ethylene dibromide (EDB) is S-[2 (N7-guanyl)ethyl]glutathione. This adduct results from the glutathione S transferase (GST)-catalyzed conjugation of EDB with glutathione (GSH), which generates an episulfonium ion capable of reacting with cellular nucleophiles. Purified rat and human GST enzymes were compared for their ability to conjugate EDB with GSH and displayed high selectivity. Of the six forms of rat GST tested, conjugation was catalyzed by the alpha class enzyme 2-2 and, to a lesser extent, by the mu class enzyme 3-3. Of the three classes of cytosolic human GST, EDB conjugation was catalyzed by the alpha class enzymes. Three dimers of the human alpha class (alpha x-alpha x, alpha x-alpha y, and alpha y-alpha y) were separated by chromatofocusing. The alpha x-alpha x preparation demonstrated the highest specific activity. Rat microsomal GST had negligible activity for the conjugation of EDB with GSH. The levels of EDB-DNA adducts formed in rat and human hepatocytes were compared. DNA was isolated from both rat and human hepatocytes incubated with 0.5 mM EDB, and the level of DNA adduct formation in the human samples was about 40% of that in the rat hepatocytes. EDB concentration dependent unscheduled DNA synthesis was demonstrated in isolated human hepatocytes. Concurrent treatment of the hepatocytes with diethylmaleate to deplete intracellular GSH inhibited EDB-induced unscheduled DNA synthesis. These results indicate that EDB alkylates DNA in human hepatocytes and that enzymatic repair of adducts may occur. The results of experiments done in rat and human systems using both purified GST enzymes and intact hepatocytes imply that the genotoxic pathway of EDB metabolism in rats and humans is similar. PMID- 2328502 TI - Accumulation of O6-methylguanine in human blood leukocyte DNA during exposure to procarbazine and its relationships with dose and repair. AB - O6-Methylguanine was measured by a competitive repair assay in blood leukocyte DNA of seven patients with Hodgkin's or non-Hodgkin's lymphoma during therapeutic exposure to procarbazine involving three daily p.o. doses (50 mg each) for 10 days (corresponding to 2.1 mg/kg/day for a 70-kg human). Adduct accumulation was observed in all seven cases, reaching levels up to 0.28 fmol/microgram of DNA (0.45 mumol/mol of guanine). In one individual, maximal levels of adduct were reached after 7 days of exposure, followed by a steady decline, whereas in all other individuals continuous accumulation was observed throughout the exposure period. In four individuals for which data were available for Day 11 (12 to 16 h after the final intake of procarbazine), decreased amounts of O6-methylguanine were observed relative to the last previous measurements. The accumulation of O6 methylguanine was linearly correlated (P less than 0.01) with the cumulative dose of procarbazine, with a slope of 0.011 fmol of O6-methylguanine/microgram of DNA per mg/kg of body weight or 2.68 x 10(-4) fmol of O6 methylguanine DNA per mg/m2. (Two h after the administration of single p.o. doses of 1 to 10 mg/kg of procarbazine to rats, O6-methylguanine formation in leukocyte DNA was just under half that in liver DNA and showed a linear relationship with dose with a slope of 0.017 fmol/microgram of DNA per mg/kg of body weight or 5.67 x 10(-4) fmol of O6 methylguanine/microgram of DNA per mg/m2. A negative correlation (P less than 0.05) between the rate of accumulation of O6-methylguanine in different individuals and lymphocyte O6-alkylguanine-DNA alkyltransferase (AGT) was observed, demonstrating a probable protective effect of AGT against the accumulation of O6-methylguanine during exposure to methylating agents. This observation supports the suggestion of a possible role of procarbazine-induced O6 methylguanine in the pathogenesis of acute nonlymphocytic leukemia appearing after treatment with chemotherapeutic protocols which include procarbazine, based on the finding of low lymphocyte AGT levels in patients with such therapy-related neoplastic disease (Sagher et al., Cancer Res., 48: 3084-3089, 1988). Lymphocyte AGT levels were mainly in the range of 5 to 10 fmol/micrograms of DNA and showed no consistent variation during procarbazine exposure. PMID- 2328503 TI - Effects of tumor necrosis factor alpha on skeletal muscle and Walker 256 carcinosarcoma protein metabolism studied in vivo. AB - Human tumor necrosis factor alpha (TNF) inhibits tumor growth, but its effects on tumor and skeletal muscle protein metabolism in vivo have not been adequately studied. Walker 256 carcinosarcoma growth rate was followed over an 11-day period in Sprague-Dawley rats. Tumor-bearing rats received either saline or 50 micrograms of TNF (Genentech, Inc.) s.c. on day 8 of tumor growth. This single dose of TNF reduced tumor protein growth during a 2-day posttreatment period from 27.6 +/- 4.4 to 10.5 +/- 3.7%/day (mean +/- SE; P less than 0.01). The rate of in vivo incorporation of L-[1-14C]leucine into skeletal muscle protein was significantly increased (P less than 0.05) from 5.1 +/- 0.2%/day in the saline treated tumor-bearing rats to 7.7 +/- 1.3%/day in the TNF-treated tumor-bearing rats. The latter value was not statistically different from the 9.2 +/- 0.9%/day observed in the tumor-free control animals. TNF administration significantly increased both the total and individual acid-soluble skeletal muscle amino acid concentrations in tumor-bearing rats by an average of 86 +/- 7%, compared to values in saline-treated tumor-bearing rats. Similarly, acid-soluble skeletal muscle 3-methyl-histidine concentrations increased from 66 +/- 14 to 113 +/- 19 pmol/g protein (P less than 0.05). Tumor protein synthesis in the TNF-treated group was 50% greater than in the saline-treated group, whether expressed as %/day (72.7 +/- 9.1 versus 47.9 +/- 4.8; P less than 0.05) or was micrograms/g tumor/min (58.7 +/- 7.7 versus 40.7 +/- 4.5; P less than 0.05). In contrast, estimated tumor protein degradation rates were increased by over 200% in the TNF treated rats, compared to the values in the saline-treated rats [62.1 +/- 10.7 versus 20.3 +/- 6.0%/day (P less than 0.01) and 50.0 +/- 8.9 versus 17.5 +/- 5.4 micrograms/g tumor/min (P less than 0.01)]. Thus, TNF appears to stimulate tumor protein degradation more than protein synthesis, explaining the overall decrease in tumor growth. PMID- 2328504 TI - Development and characterization of pediatric osteosarcoma xenografts. AB - Of 33 surgical specimens of osteosarcoma obtained from 24 patients, eight were established as transplantable tumor lines in immune-deprived CBA/CaJ inbred mice. Each line retained the histological characteristics of the corresponding primary tumor and produced human lactate dehydrogenase isozymes. Volume doubling times, which ranged from a mean of 12.3 +/- 5.6 to 39.3 +/- 9.8 days, were stable for individual lines over multiple passages. Flow cytometric analysis indicated similar cellular DNA content values in the primary human tumors and established xenograft lines; the presence of two separate stem lines, as in the original tumors, was observed in the laboratory models. Comparison of two methods of immune deprivation indicated that thymectomy, whole-body irradiation, and bone marrow reconstitution was associated with a higher rate of successful engraftment than was thymectomy, 1-beta-D-arabinofuranosylcytosine treatment, and whole-body irradiation. Bone marrow-reconstituted mice also showed less variability in tumor volume doubling time. We conclude that osteosarcoma can be heterotransplanted into bone marrow-reconstituted mice with a relatively high success rate and that the xenografts retain features characteristic of the tumors of origin. The availability of these models should prove useful in the development of new therapeutic regimens and in understanding the biology of osteosarcoma. PMID- 2328506 TI - Suppression of transformation by and growth adaptation to low concentrations of glutamine in NIH-3T3 cells. AB - NIH-3T3 cells, commonly used as targets for oncogene-mediated neoplastic transformation, undergo high rates of spontaneous transformation. When the glutamine concentration in the medium was reduced from 5 to 1 mM or less, the transformation rate was reduced. This effect was not dependent upon a reduction in the growth rate, which remained unaffected by reduction of glutamine even to 0.6 mM. Upon trypsinization and transfer to 5 mM glutamine-containing medium, cells exposed to 0.2 mM glutamine for as little as 4 days formed fewer foci than control cells exposed over a similar period to 5 mM glutamine. This indicates that short term changes in the supply of this polyfunctional metabolite have heritable consequences in later cell generations. If populations containing highly transformed cells were passaged weekly for 1-3 weeks in 0.2 mM glutamine, resultant populations were better adapted to grow in low-glutamine medium and formed fewer transformed foci upon re-transfer to 5 mM glutamine medium, suggesting that the transformed state is at least partially reversible. If similar cell populations were exposed to low-glutamine medium but were not passaged, growth adaptation occurred but there was no reduction in focus formation, indicating that maintenance of a moderate rate of cell division may be required in addition to the lowered glutamine for reversal of transformation. Transformed and non-transformed cells originating from foci and from nonfocal areas of the same culture dishes multiplied at the same reduced rate in 0.2 mM glutamine. This indicates that suppression of spontaneous transformation in low glutamine medium was not the result of selecting pre-existing variants but was itself an adaptive response of the population. PMID- 2328505 TI - Murine monoclonal antibodies against carcinoembryonic antigen: immunological, pharmacokinetic, and targeting properties in humans. AB - We have examined three 131I-labeled murine monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA), NP-2, NP-3, and NP-4, after i.v. injection in patients with diverse cancers. Although the MAbs had a similar tumor-targeting ability, several important features were discovered that have led us to the selection of one of these MAbs for further clinical evaluation. We found that it is important to evaluate MAbs with a high immunoreactivity. For example, the MAb NP-2 was used initially in patients with an immunoreactivity between 35 and 50%. Although the tumor-imaging properties of this MAb compared favorably with the affinity-purified, goat anti-CEA antibody that we used previously, further purification of NP-2 to an immunoreactivity greater than 70% uncovered a previously unknown cross-reactivity with human granulocytes. It was also discovered that the MAbs differed in their ability to complex with CEA in the blood. Plasma samples were analyzed by gel filtration at 1 or 24 h after injection. The formation of complexes with circulating CEA was dependent on the CEA:MAb ratio in the blood. NP-3 complexed to a greater degree with CEA than NP 4, but NP-2 did not complex with CEA even at CEA:NP-2 ratios of 55 to 1. NP-3 commonly showed enhanced uptake in the colon by external scintigraphy, and examination of the radioactivity in the stool showed that most of the radioactivity was associated with whole IgG and large-sized fragments of NP-3. We also compared the rate of elimination of radioactivity from the blood for all of the MAbs and compared the clearance of NP-3 to NP-4 at three different ranges of MAb protein doses (less than 1.0 mg, 1 to 5 mg, and 5 to 20 mg). The blood clearance rate for NP-3 was fastest among the other MAbs at protein doses exceeding 1.0 mg. Patients given less than 1.0 mg of NP-4 had a significantly (P less than 0.005) shorter elimination half-life than patients given more than 1.0 mg of NP-4. By virtue of NP-4's good targeting properties in patients and its limited complexation with circulating CEA, it was selected as the MAb of choice for CEA tumor imaging. PMID- 2328507 TI - Complex dystonia of Parkinson's disease: clinical features and relation to plasma levodopa profile. AB - We studied the clinical characteristics and plasma levodopa (LD) profile of complex, LD-associated dystonia in 33 patients with Parkinson's disease (PD). Generalized, abdominal, respiratory, and myoclonic, but not facial or foot, dystonia could be related to specific phases of the plasma LD cycle. Simultaneous clinical observation and determinations of plasma LD concentrations were often necessary to find the most efficacious dosing schedule for these patients. Maintenance of steady plasma LD concentrations within a dystonia-free window of benefit was the best treatment. PMID- 2328508 TI - Evidence for the role of spinal cord systems in Parkinson's disease-associated pain. AB - A patient with Parkinson's disease had severe levodopa-associated leg pain in a beginning-of-dose and peak-dose pattern. Local anesthetic block of the lumbar sympathetic chain or differential epidural block did not alter the pain. Spinal anesthesia abolished the pain. We postulate that levodopa-associated pain in Parkinson's disease either originates in or is mediated by spinal cord dopaminergic systems. PMID- 2328509 TI - Response of tertiary centres to pressure changes. Is there a mechano-electrical association? AB - STUDY OBJECTIVE: To investigate the mechanism of pressure related ventricular arrhythmias by examining them during atrioventricular (AV) block. DESIGN: Complete AV block, where all ventricular beats are ectopic, was induced by AV node ablation and/or by toxic digitalisation, and rhythm changes were studied while arterial blood pressure was repeatedly raised and lowered. SUBJECTS: 15 anaesthetised mongrel dogs, weight 15-28 kg, were used. AV block was induced in eight by chemical or mechanical ablation of the AV node. In five of these and in seven other dogs, 5.0-7.5 mg digoxin was also given. MEASUREMENTS AND RESULTS: Following AV block due to ablation, a heart rate increase (or no change) was found in 87.5% of 56 arterial pressure increases produced by elevation of an open arterial blood reservoir or by metaraminol infusion, but in only 21.8% of 55 pressure decreases caused by arterial bleeding (p much less than 0.001). Following AV block due to digitalisation, the equivalent figures were 96% of 50 pressure increases and 27.3% of 55 pressure decreases (p much less than 0.001). While arterial pressure was increased there was moderate acceleration of the escape rhythm, then appearance of premature ventricular beats, then non-sustained and finally sustained ventricular tachycardia. The reverse occurred, with some hysteresis, on decreasing the arterial pressure. In five of the digitalised animals, arterial pressure reduction to nearly zero caused reproducible sudden arrest, with resumption of the ordinary escape rhythm on increasing the pressure again. CONCLUSIONS: The findings suggest the possibility of two kinds of ectopic rhythm in AV block: the "normal" escape rhythm which is only moderately affected by arterial pressure changes; and an "abnormal" faster pressure dependent rhythm which is generated by high arterial pressure and abolished by pressure near zero, as if there were a mechano-electrical association. This abnormal rhythm may prevail completely in digitalis toxicity so that if cardiac arrest occurs, no automaticity can be expected to appear unless arterial pressure is raised. PMID- 2328511 TI - Investigation of the origin of the impedance cardiogram by means of exchange transfusion with stroma free haemoglobin solution in the dog. AB - PURPOSE OF INVESTIGATION - To determine the contribution of variations in orientation of erythrocytes (orientation effect) to the heart synchronous variations in thoracic impedance in impedance cardiography. DESIGN - The blood of four dogs was gradually replaced by stroma free haemoglobin solution, causing a decrease in resistivity and orientation effect. The decrease in orientation effect was used to determine the contribution of the orientation effect using an extended form of the "parallel conductor" model of the thorax (parallel connection of a tissue admittance Yt and a blood conductance Gb). SUBJECTS - Four adult splenectomised mongrel dogs. MEASUREMENTS and RESULTS - Packed cell volume and resistivity at body temperature of every volume of circulating fluid removed was measured. Real and imaginary parts of the transthoracic impedance and the modulus of the heart synchronous impedance variations were measured just before each exchange. The parallel conductor model was extended to account for the influence on Gb of packed cell volume and orientation of erythrocytes. Applying this extended model, the average variations in Gb at a packed cell volume of 40% were estimated to be 7.46%:3.03% due to volume variations, 4.43% due to orientation effect. After further extending the model to account for the influence of small changes in blood pressure and heart rate, the average volume variations were estimated to range from 2.8% to 3.3% and the average orientation effect from 4.1% to 4.7% at a packed cell volume of 40%. CONCLUSION - Resistivity of the blood is far from constant and the contributions of variations in blood conductivity and volume to the heart synchronous thoracic impedance are of comparable magnitude. The contribution of the volume variations is the sum of the volume variations in the contributing intrathoracic vessels. The effects of variations in orientation are added up in proportion to the relative volumes of the contributing vessels. The extensions of the parallel conductor model brought out all physiological factors determining the heart synchronous thoracic impedance variations: pulse pressures and flows, mean pressures and flows, compliances of all contributing blood vessels, packed cell volume and heart rate, as well as the relevant properties of blood: the relations between volume, flow and orientation effect and the change in orientation effect during decelerating flow. PMID- 2328510 TI - Differences in bleeding time, aspirin sensitivity and adrenaline between acute myocardial infarction and unstable angina. AB - STUDY OBJECTIVE - The objective was to measure platelet function in vivo (as cutaneous bleeding time), the role of catecholamines, and the effect of inhibiting thromboxane synthesis on bleeding time, in patients with myocardial infarction, unstable angina, and non-cardiac chest pain. DESIGN - Haemotological variables and plasma catecholamines were compared between patient diagnostic groups using the Kruskal-Wallis test, Conover's multiple comparison test, and Wilcoxon paired rank sum test. PATIENTS - 49 patients entered the study and 45 were assigned to three groups: myocardial infarction (n = 26), unstable angina (n = 9), and non-coronary chest pain (control) (n = 10). There were no significant differences between groups for age or sex. Patients with myocardial infarction smoked more than others. MEASUREMENTS and RESULTS - Compared to the controls, bleeding time in patients with myocardial infarction was shortened, while in unstable angina it was normal. Plasma adrenaline and noradrenaline concentrations were higher in the myocardial infarction group than in the unstable angina and control groups, but were not correlated with bleeding time. Bleeding time was remeasured 2 h after ingestion of 300 mg aspirin and increased in all subjects, especially in those with myocardial infarction, but it remained significantly shorter in the infarct group than in the comparison groups. Plasma adrenaline was inversely correlated with the bleeding time after aspirin in the infarct group. CONCLUSIONS - The shortened bleeding time may be an indicator of an increased prethrombotic tendency present in patients with myocardial infarction but not in those with unstable angina. The effect appears to be mediated by both thromboxane A2 and adrenaline. PMID- 2328512 TI - Inter- and intrasubject variability of the thermodilution measurement of right ventricular ejection fraction and volume in patients with chronic obstructive pulmonary disease. AB - STUDY OBJECTIVE: To determine the spontaneous changes in volumetric indices of right ventricular function assessed by thermodilution. DESIGN: The study involved measurements of inter- and intraindividual variation of right ventricular function in human subjects at rest and at two different levels of low load supine bicycle exercise. SUBJECTS: The subjects were 23 patients with chronic obstructive pulmonary disease, referred for evaluation by right heart catheterisation. Mean (SEM) age was 55.4 (2.2) years and all were in sinus rhythm. MEASUREMENTS AND RESULTS: Successive measurements of ejection fraction and right ventricular end diastolic and end systolic volumes were made by thermodilution with a fast response thermistor mounted in a Swan-Ganz catheter. Five measurements were made at rest (R), and three measurements during each of two levels of exercise (E1, E2). Group average values for each period showed no significant changes with time; interindividual variability was expressed as the coefficient of variation (VC1 = SD/means), intraindividual variability (VC2) as square root of mean value of individual variances. Interindividual variability increased from rest to exercise, while intraindividual variability was lower during exercise, presumably because the variables were more steady. For ejection fraction, VC1, was 23% at rest, 29% for E1 and 32% for E2, while VC2 was 21%, 12% and 15% respectively; for right ventricular end diastolic volume, VC1 was 23% at rest, 29% and 28% during exercise, and VC2 was 17%, 12% and 11% respectively. In some patients cold injection induced bradycardia and spuriously high values of ejection fraction. CONCLUSIONS - It is important to monitor heart rate before and during thermodilution measurements and to take into account only those made with stable heart rate. Injectate temperature should be above 10 degrees C. PMID- 2328513 TI - Inhibitory effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on the potassium current of rabbit sinoatrial node. AB - STUDY OBJECTIVE - To examine the effect of 9-amino-1,2,3,4-tetrahydroacridine (THA), a compound similar to the K+ blocker 4-aminopyridine, on potassium channels in the sinoatrial node. DESIGN - The pacemaking portion of rabbit sinoatrial nodes was studied using the double microelectrode voltage clamp method in the presence of THA at various concentrations. MEASUREMENTS AND RESULTS - Above 1 mumol.litre-1, THA prolonged the spontaneous cycle length and the transmembrane action potential duration at 50% repolarisation. Above 10 mumol.litre-1, the compound also decreased the maximum rate of rise, the action potential amplitude, and the rate of diastolic depolarisation. Under voltage clamp conditions, THA reduced the time dependent K+ current (IK) in a dose dependent manner. Neither the decay process of IK nor its activation process were altered by THA. CONCLUSIONS - THA depresses sinoatrial node IK without changing its kinetics. Thus it may inhibit the open state of the potassium channels. PMID- 2328514 TI - Raised vascular calcium in an animal model: effects on aortic function. AB - STUDY OBJECTIVE - The aim of the study was to develop an animal model to study the relationships between raised tissue calcium and vascular function. DESIGN - Ectopic calcification was developed in the animal model using chronic vitamin D2 intoxication, after which functional studies were performed in isolated superfused aortic rings. Results were compared with control preparations. EXPERIMENTAL ANIMALS - 160 female Sprague-Dawley rats weighing 200-225 g were randomly divided into experimental (vitamin D2 1 mg.d-1) and control (vehicle only) groups. MEASUREMENTS and RESULTS - Aortas from vitamin D treated animals had a higher calcium content than control aortas, without concomitant increases in cardiac calcium. Aortas with high calcium content were found to develop greater tension than control aortas when exposed to noradrenaline in the absence of extracellular calcium, but the tension maxima achieved in response to noradrenaline in calcium containing media or to high potassium depolarising solution were the same. The rate of development of contraction in response to noradrenaline was greater in aortas from the vitamin D treated animals than in controls. Isoprenaline and sodium nitroprusside produced less relaxation in the animal model aortas than in the controls. CONCLUSIONS - The results suggest that increased aortic calcium affects the response of the tissue to vasoactive agents. It appears that the additional vascular calcium may be stored in an agonist releasable pool, probably within the sarcoplasmic reticulum. The enlarged or newly developed pools appear to be refillable from the extracellular medium but not by intracellular reuptake of calcium, suggesting a bicompartmental model of intracellular calcium release and reuptake. PMID- 2328515 TI - Cardiac atria and ventricles contain different inducible adrenaline synthesising enzymes. AB - STUDY OBJECTIVE - The aim of the study was to investigate adrenaline synthesis in atrial and ventricular homogenates. DESIGN - The study involved the use of a new assay which measures the rate at which tissue homogenates convert noradrenaline into adrenaline, or dopamine into N-methyldopamine. This was coupled with a sensitive assay for tissue catecholamines in an investigation of ventricular and atrial homogenates from rats exposed to adrenal demedullation and chemical depletion of cardiac catecholamines. MEASUREMENTS and RESULTS - Atrial and ventricular homogenates from 12 male Sprague-Dawley rats were investigated. Atrial adrenaline forming activity resembled adrenal phenylethanolamine-N methyltransferase (PNMT) in its relatively high affinity for noradrenaline, substrate specificity for noradrenaline over dopamine, and inhibition by the PNMT inhibitor SKF 29661. Ventricular tissue nonspecifically methylated both noradrenaline and dopamine, and was less inhibited by SKF 29661. Adrenal demedullation induced activity of ventricular adrenaline forming enzyme. CONCLUSIONS - The cardiac atria and ventricles contain different inducible adrenaline forming enzymes. About one third of cardiac adrenaline may be synthesised by the heart itself. The ventricular enzyme can synthesise adrenaline from noradrenaline, and N-methyldopamine from dopamine. PMID- 2328516 TI - Plasma neuropeptide Y on admission to a coronary care unit: raised levels in patients with left heart failure. AB - STUDY OBJECTIVE - The aim of the study was to measure plasma neuropeptide Y, which is related to sympathetic nerve stimulation, in patients admitted to a coronary care unit and to relate the findings to clinical information. DESIGN - Plasma neuropeptide Y was measured on admission and the results were related to the cause of admission and to clinical information collected prospectively and retrospectively. SUBJECTS - Plasma subjects were obtained from 377 consecutive daytime admissions to the coronary care unit at Sodersjukhuset. Results of only the first sample in each patient are included in this study, so 45 cases observed more than once (readmitted patients) were omitted. Six samples were abandoned because of technical failures. The study therefore comprises 326 patients. Clinical diagnoses were defined as acute myocardial infarction, arrhythmia, angina pectoris, and miscellaneous (all other diagnoses). Heart failure was defined according to a modified Killip scheme. MEASUREMENTS and RESULTS - Neuropeptide Y like immunoreactivity was measured by radio-immunoassay. Plasma concentrations above normal (greater than 30 pmol.litre-1) were found in association with: increased age, female sex, diuretic treatment, tachycardia, arterial hypotension, increased respiratory rate, and mortality in the unit. There was a strong relationship between high neuropeptide Y concentrations and: moderate left heart failure (63%), pulmonary oedema (90%), and cardiogenic shock (100%). Of patients without heart failure only 25% had raised neuropeptide Y. In multivariate analysis, the severity of heart failure (Killip class), heart rate and respiratory rate were the only variables that were significantly and independently related to plasma neuropeptide Y. CONCLUSIONS - The presence and degree of circulatory disturbance, in particular tachycardia and left heart failure, were strongly related to increased plasma concentrations of neuropeptide Y in coronary care patients. PMID- 2328517 TI - Training in dogs with normal coronary arteries: lack of effect on collateral development. AB - STUDY OBJECTIVE - The aim of the study was to investigate the effect of exercise training on coronary collateral development in a normal heart animal model. DESIGN - Dogs with normal hearts were fitted with balloon occluders around the left circumflex coronary artery. Haemodynamic variables and myocardial blood flow (using radioactive microspheres) were measured during 1 min circumflex occlusions at rest and during exercise, before and after a 12 week exercise programme. Resting measurements were also made after 4 weeks. SUBJECTS - Trained subjects were 10 one year old beagles; eight beagles served as sedentary controls. Although measurements were made in all dogs at 4 weeks, four trained and three control animals died during the experiment because of complications, so the data reported at 12 weeks are derived from six trained and five sedentary animals. Except during the few occasions when the left circumflex artery was transiently occluded to allow measurement of collateral flow, all coronary arteries were patent and without impediment to normal flow. MEASUREMENTS and RESULTS - Measurements of haemodynamic variables and coronary blood flow were made at the start and repeated at 4 weeks (resting measurements only) and 12 weeks of exercise training. Initial resting circumflex collateral flow was 0.26(SEM 0.05) cm3.g-1.min-1 in the training group and 0.23(0.03) in the control group (NS). The ratio of ischaemic to normal blood flow was 0.16(0.02) in both groups. At 4 weeks there were no changes in either group. At 12 weeks the ischaemic to normal blood flow ratio had increased in both trained and sedentary dogs to 0.24(0.05) and 0.26(0.06) respectively, but the trend over the 12 week period was not significant. The decline in cardiac output and dramatic increase in left atrial pressure during combined coronary occlusion and exercise were comparable in both groups at weeks 1 and 12. CONCLUSIONS - Exercise does not accelerate the development of coronary collaterals in dogs with normal coronary arteries. PMID- 2328518 TI - Pulsatile flow and oscillating wall shear stress in the brachial artery of normotensive and hypertensive subjects. AB - STUDY OBJECTIVE - The aim of the study was to examine oscillating arterial wall shear stress in hypertension. DESIGN - Pulsatile flow and oscillating wall shear stress were measured in brachial artery in hypertensive v normotensive subjects using pulsed Doppler apparatus. Methods were tested in four subjects using a micrometric procedure of Doppler probe displacement providing instantaneous real time velocity profiles. SUBJECTS - 19 ambulatory male patients with mild to moderate hypertension (diastolic blood pressure 95-114 mm Hg) and 11 normotensive male controls of similar age were studied. All were non-smokers. MEASUREMENTS and RESULTS - Arterial diameter and pulsatile centreline blood velocity were determined with pulsed Doppler, and blood viscosity was measured with a coaxial cylinder viscometer. Shear rates corresponding to maximum (gamma Vmax), minimum (gamma Vmin), and pulse (gamma Vpulse) velocities were evaluated with a simplified method of computation of Womersley equations. Corresponding shear stresses (tau Vmax, tau Vmin, tau Vpulse) were calculated as the product between shear rate and viscosity. The differences in wall shear rates obtained with the Womersley method and with the micrometric procedure were less than 10%. Compared to normotensives, hypertensives had greater arterial diameter [0.508(SEM0.006) v 0.446(0.014), p less than 0.001], lower maximum velocity [36.2(1.5) v 46.3(2.4) cm.s-1, p less than 0.001], lower absolute value of minimum velocity [-8.3(1.2) v -14.3(2.3) cm.s-1, p less than 0.01], lower pulse velocity [44.5(2.2) v 61.2(3.9) cm.s-1, p less than 0.001], and higher blood viscosity [4.77(0.08) v 4.28(0.09) mPa.s, p less than 0.001]. gamma and tau Vmax, Vmin and Vpulse were all lower in absolute value in hypertensives. Overall mean blood pressure in all subjects was negatively correlated to gamma Vmax (r = -0.65), tau Vmax (r = -0.46), gamma Vmin (r = -0.45), tau Vmin (r = -0.37), gamma Vpulse (r = -0.63), and tau Vpulse (r = 0.48). In hypertensives, age was correlated negatively to gamma Vmax (r = -0.44), tau Vmax (r = -0.46), gamma Vmin (r = -0.57), tau Vmin (r = -0.57), gamma Vpulse (r = -0.58), and tau Vpulse (r = -0.58). In normotensives, age was not correlated with shear parameters, except for tau Vmax (r = -0.60) and tau Vpulse (r = 0.66). CONCLUSIONS - The hypertensive state is associated with a reduction in oscillating wall shear in large arteries despite an increase in blood viscosity. Age in combination with hypertension also decreases wall shear conditions. PMID- 2328519 TI - Influence of reflow ventricular fibrillation and electrical defibrillation on infarct size in a canine preparation of myocardial infarction. AB - STUDY OBJECTIVE - The aim of the study was to investigate the influence of reflow ventricular fibrillation and electrical defibrillation on infarct size in a model of myocardial ischaemia. DESIGN - Myocardial ischaemia was induced in an open chest canine model by occluding the left coronary artery for 2 h. This was followed by 6 h reperfusion. The influence of reflow fibrillation and internal electric defibrillation on infarct size was investigated and compared to dogs which did not develop fibrillation. Infarct size and its major determinants, rate pressure product (RPP), area at risk (AR), and collateral flow (MBF), were measured and their relationships studied in the two situations, using uni- and multilinear regression analysis. SUBJECTS - 21 adult mongrel dogs of either sex were used in the studies, which were done under pentobarbitone anaesthesia. Two were excluded because they developed ventricular fibrillation soon after coronary occlusion, and one did not survive reflow ventricular fibrillation. Of the remaining 18 dogs, six developed reflow ventricular fibrillation and were compared to the control group of 12 which did not develop fibrillation. MEASUREMENTS and RESULTS - A mean of 70.8(SEM 18.7) joules was required to revive the six dogs with reflow ventricular fibrillation. Difference in mean infarct size in the two groups did not reach significance [49.1(4.4) in fibrillation group v 38(6.2) in the controls]. The multiple linear regression model in the control group accounted for 91% of the variation in infarct size (IS): IS = -3.4 + 0.49 (AR) -21.8 (MBF) + 0.025 (RPP). The equation was not modified by including the reflow fibrillation dogs: IS = -3.1 + 0.52 (AR) - 19 (MBF) + 0.02 (RPP). Ischaemic determinants of infarct size in the reflow fibrillation dogs were computed in the control group equation to compare the infarct size predicted by the model to the measured infarct size in each individual dog in the reflow fibrillation group. There was no significant difference between the means: 12.9(2.9)% (predicted) v 14.9(2.5)% (measured). CONCLUSIONS - In this model of myocardial infarction, reflow ventricular fibrillation and low energy internal electric shocks do not damage the myocardium at risk significantly. PMID- 2328520 TI - Reperfusion damage: free radicals mediate delayed membrane changes rather than early ventricular arrhythmias. AB - STUDY OBJECTIVE - The aim of the study was to reassess the role of reactive oxygen species in causing reperfusion arrhythmias, which they might do either by directly generating free oxygen radicals or by using scavengers of free oxygen radicals. DESIGN - Ventricular arrhythmias were studied in isolated rat hearts (n = 8-15 per experiment) subjected to regional ischaemia and treated with various free radical scavengers and spin trap agents. Reoxygenation automaticity was similarly studied in isolated guinea pig papillary muscles (n = 6-13 per experiment). MEASUREMENTS and RESULTS - In isolated rat hearts early reperfusion ventricular arrhythmias were unaltered by superoxide dismutase (1 X 10(5) IU.litre-1), catalase (1 X 10(6) IU.litre-1), N-tert-butyl-alpha-phenylnitrone (30 mumols.litre-1), 5,5-dimethyl-1-pyrroline-N-oxide (1 mmol.litre-1), or the combination of superoxide dismutase 1 X 10(5) IU.litre-1, catalase 1 X 10(6) IU.litre-1, and mannitol 10 mol.litre-1, or by the generation of the free radical .OH (Fe:ADP plus dihydroxyfumerate). In the isolated reoxygenated guinea pig papillary muscle, the incidence of reoxygenation automaticity was significantly reduced by verapamil 5 mumols.litre-1 but not by the following free oxygen radical scavengers: reduced glutathione (0.5 mmol.litre-1), N-acetyl cysteine (1 mmol.litre-1), the combination of superoxide dismutase (3 X 10(4) IU.litre-1) and catalase (5 X 10(3) IU.litre-1), or by pretreatment with allopurinol (30 mg.kg 1). Generating systems of .O2- or .OH induced relatively slow electrophysiological changes, including a decreased action potential duration. Reperfusion ventricular fibrillation in the rat heart was increased by increasing the extracellular calcium concentration from 1.25 to 1.9 or 2.5 mmol.litre-1, or by prolongation of the ischaemic time. CONCLUSIONS - Because of (a) the lack of an arrhythmogenic effect of free radical generating systems or of scavengers of free radicals, (b) the calcium sensitivity of reperfusion arrhythmias, and (c) the relatively slow time course of electrophysiological changes induced by free radical generating systems, we propose that free radicals are unlikely to be the prime cause of early ventricular arrhythmias in the systems that we tested. The mechanism of such arrhythmias is more likely to be a calcium sensitive process. The relatively slow electrophysiological changes mediated by free radicals suggest that these agents can cause delayed membrane change. PMID- 2328521 TI - Effect of blood viscocity on arterial flow induced dilator response. AB - Experiments were designed to determine whether blood viscosity affects flow induced dilator response in conduit arteries. Changes in diameter of the femoral artery of anaesthetised cats evoked by stepwise blood flow increases were recorded at normal blood viscocity, at haemodilution, and at haemoconcentration, under conditions of stabilised transmural pressure. Dilator responses caused by the same increments in flow rate increased at haemoconcentration and decreased at haemodilution, in parallel with the changes in blood viscocity. These data show that haemodilution attenuates and haemoconcentration augments flow induced dilatation, and they confirm the suggestion that flow induced arterial dilatation is due to endothelial sensitivity to shear stress. PMID- 2328523 TI - Induction of the heat shock response in rats modulates heart rate, creatine kinase and protein synthesis after a subsequent hyperthermic treatment. AB - STUDY OBJECTIVE - The aim of the study was to examine the effect of prior induction of the heat shock response on heat shock protein synthesis and physiological variables relevant to the shock response. DESIGN - Synthesis of heat shock protein (SP71, molecular mass 71,000) was induced in rats by 15 min hyperthermia (42 degrees C). Protein synthesis, heart rate, blood pressure and creatine kinase activity were determined in comparison with controls (no heat shock) and a group receiving two heat shock treatments 24 h apart (prior induction group). SUBJECTS - 24 male Sprague-Dawley rats (125-150 g) were used, divided into three groups: controls (n = 4), heat shock X 1 (HS, n = 11), heat shock X 2 (2 X HS, n = 9). Heat shock was induced under anaesthesia on a heating pad. MEASUREMENTS and RESULTS - Blood pressure and heart rate were measured at the beginning of the hyperthermia period, when body temperature first reached 42 degrees C (t = 0 min) and at the end of the hyperthermia treatment (t = 15 min). At t = 0 min systolic blood pressure and heart rate were increased compared to the control values in both HS and 2 X HS groups. At t = 15 min heart rate in the HS group was increased to 554 (SEM21) beats.min-1 v control 465(19) (p less than 0.05). In the 2 X HS group, heart rate of 494(14) beats.min-1 at t = 15 min was not significantly different from control. At t = 15 min, creatine kinase values in the hyperthermia treatment groups were not different from control. However at 2.5 h after hyperthermic treatment plasma creatine kinase was increased in the HS group to 481(83) mU.ml-1 (n = 6) v 223(20) in controls, but was not increased in the 2 X HS group [178(64), n = 4]. Rats were radiolabelled for 2 h with 1.0 mCi of [35S]-methionine 30 min after hyperthermic treatment in HS group and 30 min after the second hyperthermic treatment in 2 X HS group. Following the 2 X HS treatment, synthesis of SP71, though increased above control values, was lower than in the HS group. CONCLUSIONS - The reduction in heart rate, plasma creatine kinase and synthesis of SP71 following a second hyperthermic exposure could be caused by a protective influence of the first exposure. PMID- 2328522 TI - Effect of hyper- and hypovolaemia on regional myocardial oxygen consumption. AB - STUDY OBJECTIVE - The purpose of the investigation was to study the effect of preload on coronary blood flow and myocardial oxygen consumption in subendocardial and subepicardial regions of left ventricular free wall. DESIGN - Ventricular volume in anaesthetised open chest dogs was altered over a range of 20% to produce hypovolaemia (10-15% exsanguination) or hypervolaemia (colloid infusion), allowing measurements of regional blood flow and oxygen consumption with varying preloads. beta Adrenergic blockade was used to limit changes in inotropy, and heart rate was kept constant by pacing at 150 beats.min-1. SUBJECTS - 9 mongrel dogs of either sex weighing 24.9 (SEM 4.1) kg were studied. MEASUREMENTS and RESULTS - Left ventricular volume was calculated from ultrasonic measurements of long and short axis end diastolic diameters and wall thickness. Regional myocardial blood flow was estimated using radioactive microspheres, and oxygen consumption in each region was determined from microspectrophotometric measurements of oxygen saturations in small arteries and veins. Hypervolaemia increased subepicardial blood flow from 66.8(6.9) (normovolaemic) to 114.1(13.5) ml.min-1.100 g-1, and regional oxygen consumption from 4.08(0.57) to 6.44(1.08) ml.min-1.100 g-1. Values in the subendocardium were similar, except for oxygen consumption, which increased less than in the subepicardium. Left ventricular end diastolic volume, pressure, and output were each increased in hypervolaemia, but not dP/dt and systolic aortic pressure. Hypovolaemia reduced blood pressures without reducing end diastolic volume. CONCLUSIONS - Augmented flow work produced by increased preload (even in the absence of changes in pressure work) increases myocardial oxygen supply equally in the subepicardium and the subendocardium, while oxygen extraction and consumption are preferentially augmented in the subepicardium. PMID- 2328525 TI - Ocular bioavailability of topical prednisolone preparations. AB - Research on the anti-inflammatory effects of prednisolone sodium phosphate and prednisolone acetate is reviewed critically and methodological problems in the study of ocular drugs are identified. A pharmacokinetic model of the absorption of water-insoluble drugs, such as prednisolone acetate, and water-soluble drugs, such as prednisolone sodium phosphate, is presented. The steps in the model are the drug elimination rate in the precornea and anterior chamber, the rate of drug dissolution, the rate of drug penetration into the cornea, and the rate of drug transport into the aqueous humor. Both prednisolone sodium phosphate and prednisolone acetate have been shown to have moderate to high anti-inflammatory effects, but it is concluded that the drug solution (prednisolone sodium phosphate) has certain advantages over the drug suspension (prednisolone acetate). PMID- 2328524 TI - Human lymphoblastoid and fibroblast interferon in the treatment of chronic hepatitis B. AB - Twenty-six patients, positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus (HBV)-deoxyribonucleic acid (DNA), and DNA polymerase activity, were treated with human lymphoblastoid interferon (IFN alpha) or human fibroblast interferon (IFN-beta) after enoxolone glycoside (glycyrrhizinic acid), given for four weeks and then withdrawn. The interferons were given continuously for four weeks. Four months after the treatment, six of 12 patients treated with IFN-alpha were both HBeAg-negative and HBV-DNA-negative while three of 14 patients treated with IFN-beta were HBV-DNA-negative and one was HBeAg-negative. None of the ten untreated control patients became negative for either HBeAg or HBV-DNA. All patients studied remained HBsAg-positive. Both interferons were generally well tolerated. A persistent low-grade fever was reported by more patients in the IFN-beta group and hair and weight loss were more common in the IFN-alpha group. The results indicate that the combination of enoxolone glycoside withdrawal and IFN-alpha treatment reduces HBV replication more effectively than does interferon alone. PMID- 2328526 TI - Nitrate tolerance: hemodynamic effects of intravenous isosorbide dinitrate after sustained oral isosorbide dinitrate administration. AB - To determine whether hemodynamic effects of isosorbide dinitrate (ISDN) diminish and disappear during sustained administration, nine patients with recent myocardial infarction received 10 mg of ISDN intravenously before and 1, 4, 12, 24, and 48 weeks after sustained oral administration of 20 mg of the slow-release form of ISDN four times daily. Blood pressure always decreased after intravenous ISDN; the decrease tended to be diminished when preceded by oral ISDN, but no further attenuation in blood pressure was noted. The decrease in blood pressure was associated with consistent and nonsignificant increases in heart rate after intravenous ISDN. Plasma ISDN levels were not affected by prior oral ISDN. Plasma isosorbide 2-mononitrate and isosorbide 5-mononitrate levels were consistently higher when preceded by oral ISDN. The results suggest that the hemodynamic and metabolic properties of ISDN are preserved even after sustained therapy. PMID- 2328527 TI - Ofloxacin in the treatment of typhoid fever unresponsive to chloramphenicol. AB - Chloramphenicol was used to treat confirmed typhoid fever in 50 patients, but 14 patients did not respond to treatment. When their treatment was changed to ofloxacin (400 mg twice daily for six days, followed by 200 mg for eight days, administered orally), all responded. Ofloxacin was well tolerated and appears to be an effective agent in the treatment of typhoid fever. PMID- 2328528 TI - Natural killer cell-mediated lysis of herpes simplex virus-infected fibroblasts: inability to detect soluble factors that contribute to lysis. AB - We investigated the role of soluble factors in natural killer (NK) cell-mediated lysis of herpes simplex virus (HSV)-infected cells. Supernatants generated by incubating human peripheral blood mononuclear cells with HSV-infected human fibroblasts contained tumor necrosis factor (TNF) and lysed uninfected U937 cells, but not HSV-infected fibroblasts. U937 cells, but not HSV-infected fibroblasts, were lysed when exposed to recombinant TNF (rTNF) for 18 hr. NK cell mediated lysis of HSV-infected fibroblasts was not inhibited by addition of anti TNF or anti-lymphotoxin (LT) antibodies to cytotoxicity assays. Thus, a role for soluble factors, and in particular TNF and LT, in NK cell-mediated lysis of HSV infected cells could not be demonstrated. PMID- 2328529 TI - Quantitative analysis of bone marrow thymic progenitors in young and aged mice. AB - Our studies on the capacity of bone marrow (BM) to generate T lymphocytes in aging have revealed that under the competitive conditions of thymic reconstitution, cells of aged mice are significantly inferior to those of the young. The present study was designed to further investigate the basis of this age-related change. Two mechanisms were considered: (a) The potential of BM derived T cell precursors from aged mice to proliferate and differentiate in the thymic microenvironment is impaired. (b) The frequency of T cell precursors is reduced in BM of aged mice, thus affecting their ability to compete efficiently in reconstituting the thymus. These possibilities were studied in vitro by colonizing thymocyte-depleted fetal thymic lobes with BM cells from aged (24 month) and young (3-month) C57BL/6 mice. By determining the cell cycle duration of BM-derived cells which have seeded the thymic lobes, we found that cells originating from aged mice proliferate in the thymus at the same rate as those from young mice. Reconstitution with limiting numbers of BM cells indicated that the frequency of thymic progenitors in the BM is significantly reduced in aged as compared to young mice. We thus conclude that aging is associated with a quantitative reduction in the frequency of thymic progenitors in the BM. PMID- 2328530 TI - Alterations in cell-surface carbohydrates of rat large granular lymphocytes associated with interleukin-2 activation. AB - The activation of large granular lymphocytes (LGLs)/natural killer (NK) cells with interleukin-2 (IL-2) has been shown to increase the ability of these cells to lyse NK-resistant tumor target cells. Activated LGLs, termed LAK (lymphokine activated killer) cells, have been demonstrated to be of therapeutic value in vivo against metastatic tumors. The mechanism by which IL-2 induces broadened cytolytic capability, as well as the molecular basis of target recognition and killing by the activated cells has not yet been elucidated. Since carbohydrate moieties have been demonstrated to be of possible significance in the cytolytic cascade of a variety of effector cells, the current study was undertaken to determine if the activation of LGLs with IL-2 is accompanied by an alteration of cell-surface carbohydrates. Two-color flow cytometry was performed to identify LGL/NK cells in populations of nylon wool-nonadherent splenic mononuclear cells and to assess the binding of various lectins to activated as well as nonactivated LGLs. Increases were observed in the binding of four lectins to LGLs after IL-2 activation; Triticum vulgaris (wheat germ agglutinin), Phytolacca americana (pokeweed mitogen), Lycopersicon esculentum (tomato lectin), and Griffonia simplicifolia I-B4 (GSI-B4). The wheat germ, pokeweed, and tomato lectins recognize complex carbohydrates structure consisting of GlcNAc(Bl,4GlcNAc)n while GSI-B4 recognizes alpha-D-galactose terminal end groups. Lectin binding to the activated LGLs was homogenous (i.e., flow cytometry revealed only a single population of fluorescent cells). Lectin binding to LGLs prior to activation was more heterogeneous, however, the tomato lectin uniquely revealed a bimodal distribution of receptors. These data indicate that LGL/NK cells from the rat are heterogeneous in their ability to bind specific lectins, and that IL-2 activation of these cells results in altered expression of specific cell-surface carbohydrates. PMID- 2328531 TI - Activation of maternal killer cells in the pregnant uterus with chronic indomethacin therapy, IL-2 therapy, or a combination therapy is associated with embryonic demise. AB - We have previously shown that NK lineage cells migrate to the murine decidua of pregnancy; but with advancing gestation, they are progressively inactivated in situ by prostaglandins of the E series (PGE2) secreted by decidual cells and decidual macrophages. We have also shown that the same mechanism inactivates all killer lineage cells in the human decidua, and that this inactivation is at least in part due to a down-regulation of IL-2 receptors and an inhibition of IL-2 production in situ. We examined whether chronic indomethacin therapy (to block prostaglandin synthesis), or a systemic administration of a high dose of IL-2, or a combination of both agents administered to pregnant mice could activate killer cells in situ and interfere with the progress of pregnancy; and if so, whether there was a causal relationship between the two events. Pregnant CD1 mice (Day 5 of gestation) were subjected to chronic indomethacin therapy (14 micrograms/ml in drinking water up to Day 15, or 50 micrograms twice daily sc or ip up to Day 10), high dose IL-2 therapy (25,000 Cetus U of human recombinant IL-2, ip every 8 or 12 hr for 3-5 days), or a combination of the two. These treatments led to pregnancy loss in 89-100% of mice, in contrast to 1% loss in control, vehicle treated mice. Uterine mononuclear cells isolated from the embryo resorption sites exhibited high killer activity against YAC-1 lymphoma as well as murine trophoblast targets, with NK-like phenotype (Asialo GM-1+, Thy-1-) after indomethacin therapy and LAK-like phenotype (AGM-1+, Thy-1+) after IL-2 or indomethacin + IL-2 therapy. That AGM-1+ killer cells resulted in the pregnancy loss was suggested by the findings that in two of three separate experiments, iv injections of AGM-1 ab into pregnant indomethacin + IL-2-treated mice nearly completely prevented the fetoplacental demise (reducing it to 7.7% from 100%). These results reveal that PGE2-mediated inactivation of killer lineage cells in the decidua in situ is conducive to the survival of the conceptus. PMID- 2328532 TI - Binding of low-density lipoproteins from chicken egg yolk to mouse anti phospholipid B cells which include B cells against bromelain-treated mouse erythrocytes. AB - Low-density lipoproteins from chicken egg yolk (EyLDL), which are reactive with mouse antibodies against bromelain-treated mouse erythrocytes (BrMRBC), were conjugated with fluorescein isothiocyanate (FITC). FITC-EyLDL could bind specifically to mouse anti-phospholipid B cells, which comprised all the BrMRBC rosette-forming cells and anti-BrMRBC lipopolysaccharide-reactive B cells, C3H/He mice at 12 weeks of age had, approximately, 7 x 10(5) EyLDL-binding cells in the peritoneal cavity, 3 x 10(5) EyLDL-binding cells in the pleural cavity, and 3 x 10(5) EyLDL-binding cells in the spleen. In ontogeny, the numbers of EyLDL binding cells in the peritoneal cavity expanded greatly by 4 weeks. Other normal strains of mice and C3H/HeJ mice at 12 weeks of age had 4-7 x 10(5) EyLDL-binding cells in the peritoneal cavity; the numbers were large (19 x 10(5] in NZB mice, rather small (2 x 10(5] in MRL/lpr mice, and very small (0.1 x 10(5] in CBA/N mice. In some of various strains of mice at 12 months of age, more than 20% of peritoneal cells were EyLDL-binding cells; in particular, all of five older NZB mice examined had more than 10(7) EyLDL-binding cells in the peritoneal cavity. PMID- 2328533 TI - Feedback by early and late primary antisera on the primary and secondary adoptive immune responses of mice to burro erythrocytes. AB - Experiments on antibody feedback inhibition of the immune response have confirmed that control is more effective against a primary response than against a secondary response. The cells producing antibodies in primary and secondary responses are different both in terms of number of IgFC and amount of antibody produced by individual IgFC (plaque size). Late primary anti-burro RBC sera (greater than 200 days), despite low titers, are, on a volume for volume basis, feedback inhibitors at least as good as early (8-12 days) primary antisera on primary responses but are more effective in suppressing secondary responses (B memory cells). Late primary antisera, due to the process of affinity maturation, have a high affinity for antigen. The suppressive effect of early and late antisera is equally removable by absorption with burro erythrocytes: a result which it is thought, decreases the likelihood of feedback by anti-idiotype being involved in the observed suppression. It is suggested that feedback antibody acts (a) in competition with receptors, inter alia removing antigen into immunologically irrelevant pathways, (b) by a process involving the linking of antigen to Fc receptors, and (c) as a blocking antibody coating B cells (Bm) or APC which are already binding epitopes, thus preventing their cooperation with specific helper or other accessory cells. PMID- 2328534 TI - A novel role for accessory cells in T cell-dependent B cell differentiation. AB - The monocyte requirement for pokeweed mitogen-induced T cell-dependent B cell activation was reexamined. We report a dichotomy in the requirement for accessory cells in B cell proliferation and differentiation. Adherent cell-depleted human peripheral blood mononuclear cells which contained only 5% monocytes generated sufficient T cell help for optimal B cell proliferation. However, the presence of 10 to 20% monocytes were required during the last 5 days of culture for stimulated B cells to become IgG-secreting cells. Similar numbers of monocytes were also needed for anti-CD3-induced B cell differentiation. Moreover, monocytes alone added to previously activated B cells could support B cell differentiation in the absence of T cells. To determine the role of cytokines in this system, we demonstrated that supernatants of adherent cell-depleted PBMC contained decreased IL-6 activity in comparison with unseparated PBMC, but not IL-1, IL-2, or BCGF. Recombinant IL-6, however, added back either alone or with other cytokines could not replace the effects of intact monocytes on B cell differentiation. Physical interaction between the accessory cells and the responder cells was also required. As a minimum, paraformaldehyde-fixed monocytes, IL-6, and IL-1 were needed to reconstitute maximal IgG secretion. These studies suggest that accessory cells capable of producing IL-1 and IL-6 can have direct effects on the terminal differentiation of stimulated B cells. PMID- 2328535 TI - Molecular signals in B cell activation. I. Differential refractory effects of incomplete signaling by ionomycin or PMA relate to autocrine IL-2 production and IL-2R expression. AB - The molecular signals required by resting (G0) B cells for the induction of cell cycle entry, IL-2 production, and high-affinity IL-2 receptor (IL-2R) expression were defined and the effects of incomplete activation signals on the subsequent response to complete signals were examined. Highly enriched rabbit peripheral blood B cells were activated with a calcium ionophore, ionomycin, and a protein kinase C (PKC) activating phorbol ester, phorbol myristate acetate (PMA). It was observed that cell cycle entry to early G1 was induced by either reagent acting alone, but both reagents were required to stimulate IL-2 production, IL-2R expression, and DNA synthesis. These effects of ionomycin and PMA were shown to be mediated by increased intracellular calcium ion concentration [Ca2+]i and PKC activation, respectively. Although, increased [Ca2+]i or PKC activation each led to cell cycle entry, the subsequent response of these preactivated cells to complete activation with both signals was different: Cells pretreated with PMA alone for up to 24 hr could progress further to DNA synthesis after the addition of ionomycin. In contrast, cells activated with ionomycin alone, or those cultured without any stimulus, progressively lost the ability to show DNA synthesis after complete activation. The failure to progress to DNA synthesis in these two cases was, however, differentially regulated by the ability of these cells to produce IL-2 and to express IL-2R. Ionomycin-pretreated cells retained the ability to produce IL-2 but showed about 70% reduction in the numbers of IL 2R; whereas cells cultured without any stimulus lost the ability to produce IL-2 after subsequent complete activation, but showed lesser reduction in IL-2R expression. PMID- 2328537 TI - Shark cytotoxic macrophages interact with target membrane amino groups. AB - The types of target structures recognized by cytotoxic macrophages have been described for various microorganisms, but have not been defined for tumor cells. Tumoricidal macrophages are selective in their destructive mechanisms, sparing normal cells while directing their lytic machinery toward neoplastic targets. The cytotoxic activity of macrophages from a primitive vertebrate, the nurse shark, closely resembles the activity of mammalian tumoricidal macrophages. Host defense mechanisms of these animals appear to rely on antigen nonspecific cellular effector systems, and it has been postulated that macrophage-mediated cytotoxicity plays a dominant role in protection during periods of decreased environmental temperatures when lymphocyte responses of poikilothermic vertebrates are compromised. Similar to mammalian tumoricidal macrophages shark macrophages display selective recognition of target cells. Previous studies showed that TNP modification of targets was protective, preventing recognition by the shark spontaneously cytotoxic macrophage. Additionally, it was shown that cytotoxic activity was inhibited in a dose dependent fashion by the addition of excess unlabeled targets. In the present study, similar inhibition experiments with hapten-modified targets have been used to determine the nature of the target structures recognized by the shark cytotoxic macrophage. Cold targets modified with haptens which react covalently with free amino groups on cell membranes, trinitrobenzene sulfonic acid (TNBS) and flourescein isothiocyanate (FITC), are not recognized by the cytotoxic macrophage. The relative amount of membrane bound TNP was correlated with inhibition of cytotoxicity. Conversely, target cells modified with sulfhydryl reacting reagents, N-iodoacetyl-N'-(5-sulfonic-1 naphthyl) ethylene diamine and dithionicotinic acid, are recognized similarly to untreated targets. Moreover, TNP-containing lipids, permitted to diffuse into target membranes without covalent binding, do not alter target recognition, indicating that TNP itself has no effect on macrophage:target interaction. From these data, it is concluded that the shark cytotoxic macrophage interacts with membrane bound amino, but not sulfhydryl groups. The ability to distinguish between membrane structures may have appeared early in evolution as a means of preserving self cells while retaining protective nonspecific cytotoxic mechanisms. PMID- 2328536 TI - Molecular signals in B cell activation. II. IL-2-mediated signals are required in late G1 for transition to S phase after ionomycin and PMA treatment. AB - We report that sustained increase of intracellular calcium ion concentration and protein kinase C (PKC) activation maintained throughout the G1 phase of cell cycle do not provide sufficient signals to cause S-phase entry in rabbit B cells, and that additional signals transduced by IL-2 and IL-2 receptor interaction are essential for G1 to S transition. We have shown earlier that rabbit B cells can be activated to produce IL-2 and express functional IL-2 receptors after treatment with ionomycin and PMA. Herein we have compared the response of rabbit PBLs, which contain about 50% T cells, with those of purified B cells. After activation with ionomycin or PMA, comparable numbers of PBLs and B cells entered the cell cycle; but DNA synthesis by the PBL cultures was three to four times higher than that of cultures of purified B cells. Interestingly, IL-2 production by the PBL cultures was also three to four times higher than in B cell cultures, suggesting an involvement of IL-2 in inducing DNA synthesis in these cells. The hypothesis that IL-2, which is produced in early G1, acts in late G1 and is required for G1 to S transition in B cells was supported by the following observations: (i) IL-2 production by B cells was detected as early as 6 hr after activation and preceded DNA synthesis by at least 24 hr. (ii) B cell blasts in G1 (produced by treatment of resting B cells with ionomycin and PMA) showed DNA synthesis in response to IL-2, but showed very little DNA synthesis in response to restimulation with ionomycin and PMA. (iii) A polyclonal rabbit anti-human IL 2 antibody caused nearly complete inhibition of DNA synthesis by B cells activated by ionomycin and PMA. (iv) A PKC inhibitor, K252b, inhibited DNA synthesis in ionomycin and PMA-stimulated cells if added at the beginning of culture but was not inhibitory if added 16 hr later. We conclude that increased [Ca2+]i and PKC activation are not sufficient signals for G1 to S transition in B cells; entry into S is signaled by IL-2, and IL-2-mediated signal transduction probably does not involve increased [Ca2+]i or PKC activation. PMID- 2328538 TI - Lymphoma models for B cell activation and tolerance. VIII. Cross-desensitization by sIgM and sIgD and its effects on growth regulation by anti-isotype antibodies. AB - ECH408-1 is a murine B cell lymphoma expressing idiotypically and allotypically distinguishable transfected and endogenous IgD. Previously, we demonstrated that this cell line was not growth inhibited by antibodies directed at membrane IgD, but could be inhibited by antibodies which crosslink membrane IgM. Herein, we demonstrate that both anti-mu and anti-delta will cause calcium mobilization in this transfected cell line; this is followed by a period during which antibodies against the alternative isotype are unable to induce significant increases in intracellular calcium concentrations. This phenomenon, called "desensitization," is short-lived, lasting 20 min. We further demonstrate that acute desensitization of these cells by anti-delta has no effect on immediate growth inhibition which is elicited by anti-mu. These data confirm our earlier proposal that the rapid, initial calcium response seen in these lymphomas is not required for the negative signal for growth. Moreover, we also demonstrate that pretreatment of these lymphoma cells with phorbol myristate acetate (PMA) also renders these lymphoma cells temporarily incapable of manifesting a significant calcium signal. Nonetheless, PMA-pretreated B lymphoma cells are not altered in their subsequent sensitivity to anti-mu growth inhibition, nor are they affected in their resistance to inhibition by anti-delta. Our data confirm the proposal that neither the calcium signal nor protein kinase-C activation is involved in the modulation of B lymphoma growth. PMID- 2328540 TI - Neurovascular injuries. PMID- 2328539 TI - Electrodiagnostic testing of neurologic injuries in athletes. AB - In this article the value and limitations of the EMG examination in assessing patients with known or suspected sports-related nerve injuries is reviewed. The basic components of the EMG examination--the nerve conduction studies (NCS) and the needle electrode examination (NEE)--are described, and their components are defined. The types of pathophysiology produced by focal nerve lesions is detailed, and their effects on the various portions of the EMG examination are described. Of note is that the two processes that cause clinical weakness, conduction block and conduction failure (axon loss), both alter the NCS amplitudes, without having any appreciable effect on the rate of impulse conduction along the nerve fibers that can still conduct across the lesion site. For this reason, the most widely known NCS parameter, the conduction velocity, is of very little value with the acute type of nerve lesion usually encountered in sports. The fact that fibrillation potentials, seen on NEE, are the most sensitive indicator of motor axon loss, is noted, as is the fact that they do not appear until some 3 weeks following nerve injury. Our EMG laboratory experience with sports-related nerve injuries is reviewed. The majority of patients were engaged in contact sports (especially football). The majority of lesions affected primarily the shoulder girdle region, although a variety of disorders (radiculopathies, brachial plexopathies, various mononeuropathies) were found. Some of the difficulties in the EMG assessment of this region are reviewed, as well as the clinical and EMG findings with three entities, "burners," acute brachial neuropathy, and rotator cuff tears, which affect it and which occur in athletes. PMID- 2328541 TI - Cervical spine injuries and their neurologic implications. AB - This article presents the neurologic implications of cervical spine injuries by reviewing (1) cervical spine anatomy, (2) initial patient evaluation, (3) the type of neurologic injuries that can occur, (4) the treatment of athletes with these injuries, and (5) criteria for returning to activity. PMID- 2328542 TI - Effects of strophanthidin on the slow inward current in guinea-pig isolated ventricular myocytes. AB - 1. The effect of strophanthidin on the slow inward current (Isi) and on contractile force were studied in guinea-pig isolated ventricular myocytes and intact papillary muscles, respectively. In myocytes, both low (10 nmol/L) and high (1-10 mumols/L) concentrations had small or no effects in either direction on Isi whereas norepinephrine (10-100 nmol/L) increased it. To determine whether the same results are obtained after decreasing or increasing intracellular calcium or sodium, the same concentrations of strophanthidin were tested in different procedures that are known to (i) increase [Ca]i and decrease [Na]i (high [Ca]o, 3.6-5.4 mmol/L; low [Na]o, 112 mmol/L; (ii) decrease [Ca]i and increase [Na]i (low [Ca]o, 0.45-1 mmol/L; Sr, 1 mmol/L; (iii) decrease [Ca]i and [Na]i (Cd, 0.1-0.2 mmol/L); and (iv) increase [Ca]i and [Na]i (veratridine, 0.2 mumol/L). High [Ca]o and veratridine increased whereas low [Ca]o and Cd decreased Isi. In contrast, during these various procedures, strophanthidin had small and inconsistent effects at a low or high concentration. In intact papillary muscles, low strophanthidin decreased whereas high strophanthidin increased contractile force. It is concluded that strophanthidin has little direct or indirect effect on Isi and that the decrease in force by low and increase in force by high concentrations in intact muscle are probably related to demonstrated decrease and increase, respectively, in intracellular sodium activity. PMID- 2328543 TI - Changes in saline and water intakes in bromocriptine-treated genetically hypertensive and normotensive rats. AB - 1. We have previously reported on the effects of a 13-day intraperitoneal infusion of bromocriptine delivered by osmotic pump on blood pressure, plasma and pituitary PRL levels in genetically hypertensive (GH) rats and their normotensive (NT) controls. This paper reports further on that study in describing the changes in saline and water intakes in rats as a result of bromocriptine (BRC) treatment. 2. In the GH rats, bromocriptine did not have any significant effect on saline or water intake. 3. In the NT rats, bromocriptine significantly decreased saline intake and increased water intake. 4. The saline intake in the vehicle-treated GH rats was significantly lower than that in the vehicle-treated NT rats while the water intake was not significantly different. 5. These results indicate that differences exist between the GH and NT rats with regard to their saline and water intakes and their responses to chronic bromocriptine treatment. The changes in saline and water intakes in the GH rats seem to be different from those seen in the spontaneously hypertensive rat in another study. PMID- 2328544 TI - Nicotinic agonist modulation of feline bronchomotor tone. AB - 1. The bronchomotor actions of three nicotinic cholinoceptor agonists were investigated in anaesthetized, mechanically ventilated cats. The agonists were administered intravenously after increasing baseline airways smooth muscle tone with an infusion of 5-hydroxytryptamine. 2. Acetylcholine induced a biphasic change in lung resistance, characterized by initial bronchoconstriction followed by bronchodilation. The specific nicotinic cholinoceptor agonists, nicotine and dimethylphenylpiperazinium (DMPP), principally induced bronchodilator responses, although initial bronchoconstrictor phases were observed occasionally. 3. All bronchoconstrictor phases were sensitive to muscarinic cholinoceptor blockage with atropine. DMPP-induced bronchodilator responses were adrenergic in nature, whereas those induced by either nicotine or acetylcholine resulted from a combination of adrenergic and non-adrenergic influences. 4. It is concluded that intravenously administered nicotinic cholinoceptor agonists exert varying actions on feline bronchomotor tone and that these actions result from activation of different autonomic inputs. PMID- 2328545 TI - Rat duodenal smooth muscle contractile responses to angiotensin II are dependent on calmodulin. AB - 1. Isolated duodenal segments were pretreated with either of the calmodulin inhibitors proadifen or trifluoroperazine and the subsequent contractile force and frequency response to angiotensin II monitored. 2. Both proadifen and trifluoroperazine decreased the spontaneous contractile force and frequency in isolated perfused duodenal segments and attenuated the force generation following exposure to angiotensin II. Proadifen and trifluoroperazine also altered the qualitative behaviour of duodenal segments. 3. These results suggest that the action of angiotensin II on duodenal smooth muscle motility is dependent on calmodulin. Furthermore, the change in qualitative behaviour of duodenal segments following treatment with calmodulin inhibitors suggest that the function of intrinsic intestinal neurons is also altered. PMID- 2328546 TI - Differences in organization of metastatic and nonmetastatic tumors initiated by the same B16 melanoma clone in mature and young mice. AB - Subcutaneous transplants of mouse B16 melanoma clone G3.26 grow more slowly, and are markedly more metastatic to the lungs, in mature (greater than 12-month-old) mice than in young (2-month-old) mice. Previous studies suggested that tumors in young mice fail to disseminate viable tumor cells into the hematogenous circulation. To determine if changes in intratumor organization might accompany this altered tumor behavior, G3.26 tumors growing in young and mature mice were examined comparatively at progressive sizes relative to the onset of metastatic dissemination in the older mice. Although the degree of necrosis was comparable in both groups of tumors, vascular density, measured morphometrically in histological sections, was significantly lower in tumors from mature mice at a size when dissemination would be occurring. With the onset of reduced vascular density in tumors in mature mice, there was a substantial increase in the proportion of viable tumor cells that was hypoxic, based on radioresistance and incorporation of the hypoxic cell sensitizer, misonidazole. Quiescent tumor cells, identified by flow cytometry, were also more numerous in tumors from mature mice than in tumors from young mice. Although the importance of these differences in tumor organization to enhanced metastatic behavior is unclear, increased intratumor hypoxia might promote generation of metastatic variants. Alternately, dissemination of tumor cells might be facilitated through a reduced and possibly defective vasculature. PMID- 2328547 TI - Culture of PNKT-4B cells at invasion permissive and restrictive temperatures. I. Chromosomal analysis. AB - PNKT-4B is an aneuploid cell line derived from a herpesvirus-induced renal adenocarcinoma of Rana pipiens that displays restricted invasion at 21 degrees C or cooler and invasion at 23 degrees C through 28 degrees C. Metaphase chromosomes obtained from subcultures (passages 297; 345-347) grown at 18 degrees C or 28 degrees C were Giemsa stained or N-banded with acidic silver nitrate. Cells grown at 18 degrees C displayed a modal chromosome number of 41, while 28 degrees C cultures displayed a modal number of 40. The distribution of the chromosomes suggests that the two temperatures may be allowing growth of different subclonal populations. N-banding of chromosomes at both temperatures revealed an increase of active nucleolar organizer regions (NORs) over normal frog tissues, 2/2N. Analysis of 200 N-banded spreads from cells grown at each temperature revealed modal numbers of 9 NORs/cell and modal numbers of 6 NOR containing chromosomes/cell. Nine specific NOR-containing chromosomes were identified and scored. Similar distributions were observed at 18 degrees C and 28 degrees C. The data imply that the modal number of PNKT-4B has shifted since it was first described, 39, and differs at invasion-permissive and -restrictive temperatures. Increased numbers of active NORs and alterations of NOR-containing chromosomes imply an amplification of rDNA over the amount in normal frog. PMID- 2328548 TI - Lectin-resistant variants of mouse Lewis lung carcinoma cells. I. Selection and in vivo properties. AB - The availability of lectin-resistant cell lines with altered carbohydrate moieties in cell surface glycoproteins and glycolipids has greatly facilitated study of the involvement of cellular glycoconjugates in tumor growth and metastasis. We present here a new animal model for metastasis study based on mouse Lewis lung carcinoma LL2 in vitro cell line. From this line, five lectin resistant variant sublines were selected with the following lectins: wheat germ agglutinin (WGAR), Ricinus communis agglutinin II (RCA IIR) and Aleuria aurantia agglutinin (AAAR). The correlation of the lectin resistance with their in vitro and in vivo growth properties, and especially lung colonizing ability, were investigated. Three WGAR variants with well-preserved tumorigenicity revealed reduced metastatic ability, both spontaneous, after subcutaneous (s.c.) administration and experimental, after intravenous (i.v.) administration. The RCA IIR variant also possessed reduced spontaneous and experimental metastatic ability, but exhibited higher growth rate of local s.c. tumors. The AAAR variant possessed reduced spontaneous metastatic ability but its ability to colonize the lungs after i.v. administration was five-fold higher than that of the parent LL2 line, whereas its tumorigenicity remained unchanged. The relative differences among WGAR variants and parent LL2 line, concerning their experimental metastatic ability, remained similar in cyclophosphamide-modified mice to those in normal recipients. PMID- 2328549 TI - Lectin-resistant variants of mouse Lewis lung carcinoma cells. II. Altered glycosylation of membrane glycoproteins. AB - Lectin-resistant variants of mouse Lewis lung carcinoma LL2 cell line, selected with wheat germ agglutinin (WGAR), Ricinus communis agglutinin II (RCA IIR) and Aleuria aurantia agglutinin (AAAR) were studied. Total cellular glycopeptides of the parent LL2 line and of the five lectin-resistant variants were analyzed by gel filtration and affinity chromatography on immobilized concanavalin A and Lens culinaris agglutinin. The results revealed that low-metastatic WGAR and RCA IIR variants possessed less highly branched tri- and tetra-antennary N acetyllactosaminic type glycans with a simultaneous increase in biantennary N acetyllactosaminic type, oligomannosidic type or hybrid type glycans, as compared to the parent metastasizing LL2 cell line. These findings imply that cell surface carbohydrate changes may possibly be relevant for metastasis. However, the AAAR variant, which possessed reduced spontaneous metastatic ability after s.c. administration, but increased experimental metastatic ability after i.v. inoculation, exhibited apparently the same glycan pattern than the parent LL2 line. This particular variant is under investigation in order to find specific modification(s) of glycan(s) which could play a specific role in the metastatic process. PMID- 2328550 TI - Transcutaneous theophylline collection in preterm infants. AB - Transcutaneous collection of theophylline and its metabolite, caffeine, was undertaken in 33 preterm infants (2 to 89 days old) who were receiving routine theophylline therapy. Collection was done by means of a novel adhesive transcutaneous collection system. The transcutaneous collection system accumulated substances that migrated from the blood to the skin surface by trapping them in an activated charcoal-gel matrix. On one to three occasions, four transdermal collection systems were applied to the back or abdomen of each infant for 4 to 12 hours. During that time, blood samples were obtained for routine monitoring of plasma theophylline levels. Amounts of theophylline (95 +/- 198 ng) and caffeine (83 +/- 77 ng) in the transcutaneous collection system were significantly correlated with the respective average plasma drug concentration and postconceptional age (p less than 0.01). Skin reactions were limited to mild erythema. We concluded that theophylline and caffeine can be collected on the surface of the skin of preterm infants with a novel transcutaneous collection system. Amounts collected by means of the transcutaneous collection system correlated with plasma concentrations consistent with a diffusion process, but they were poor predictors of individual concentrations. PMID- 2328551 TI - Influence of tretinoin on the percutaneous absorption of minoxidil from an aqueous topical solution. AB - Nineteen healthy male volunteers completed a three-way, randomized, crossover study to determine the effect of the synthetic retinoid, tretinoin, on percutaneous absorption of minoxidil. Subjects received, for 20 days, twice-daily administrations of 1 ml of an aqueous 2% topical minoxidil solution either alone, with once-daily applications of a 0.05% tretinoin cream, or with once-daily applications of a vehicle control cream. When minoxidil was coadministered with tretinoin cream, minoxidil absorption was increased nearly threefold, compared with a 1.3-fold increase in absorption observed with coadministration of vehicle control cream. Transepidermal water loss measurements, which are sensitive to changes in stratum corneum function, were also significantly increased with tretinoin. No treatment-related changes in stratum corneum thickness were observed on the basis of skin biopsy analysis. The findings indicate that percutaneous minoxidil absorption is enhanced by tretinoin as a result of increased stratum corneum permeability. PMID- 2328552 TI - Effects of age on the protein binding and disposition of propranolol stereoisomers. AB - Previous studies of the effects of age on the disposition of propranolol have produced variable results. We evaluated the stereoselective disposition and protein binding of propranolol enantiomers in 10 young (mean age, 28 years) and 10 older (mean age, 64 years) healthy subjects. After receiving racemic propranolol orally for 6 days, the oral clearances of d-propranolol and l propranolol were lower by 13% and 17% in the older group compared to the young group, but these differences were not statistically significant. The older subjects had higher alpha 1-acid glycoprotein concentrations (p less than 0.05) and lower unbound fractions of l-propranolol (p less than 0.05). After protein binding was accounted for, the unbound oral clearance of each enantiomer was similar in both groups. l-Propranolol was more highly protein bound than d propranolol (p less than 0.05) in both young and older subjects. The unbound oral clearance d/l ratio was not different from unity in either group, indicating that the stereoselective differences in oral clearance were largely attributable to the stereoselective differences in protein binding. PMID- 2328553 TI - Inhibitory effects of the new PAF acether antagonist WEB-2086 on pharmacologic changes induced by PAF inhalation in human beings. AB - Recent research on asthma mediators has concentrated more and more on platelet activating factor (PAF), which is one of the most potent bronchoconstrictors known thus far. Inhalant PAF challenge in healthy volunteers may provide a mean of testing PAF antagonists. The usefulness of the PAF provocation test in measuring the pharmacologic activity of a new PAF antagonist, WEB-2086, has been examined in 12 healthy volunteers in a double-blind, placebo-controlled, within subject crossover study. PAF-induced immediate bronchoconstriction, slight hemodynamic changes, and PAF-related subjective side effects. Premedication with WEB-2086 (40 mg) completely prevented any increase in airway resistance after PAF inhalation, as well as development of most of the cardiovascular and side effects induced by PAF. The clear protection against PAF-induced pharmacologic effects can be explained by the specific PAF-antagonistic activity of WEB-2086. The method described in this article may be applied as a useful tool for looking at PAF-antagonistic activity in healthy volunteers. PMID- 2328554 TI - The effect of hepatic cirrhosis on the pharmacokinetics and blood pressure response to nicardipine. AB - The present study was designed to compare the pharmacokinetic handling of a single oral dose of nicardipine in normal subjects and in patients with hepatic cirrhosis and to compare the sensitivity of the two groups to its hypotensive effect. Nicardipine plasma concentrations were substantially higher in the subjects with hepatic cirrhosis with impaired antipyrine clearance, as shown by a significantly higher average Cmax and AUC. The terminal elimination half-life in this group varied from 0.8 to 60.2 hours (median, 11.7 hours), compared with 0.6 to 4.1 hours (median, 1.4 hours) in the group of eight subjects with normal liver function. In the cirrhotic patients with impaired antipyrine clearance, the AUC of the pyridine metabolite averaged 10% of that of the parent drug, whereas in normal subjects the ratio averaged 48%. This finding suggests less conversion of nicardipine to this metabolite in subjects with impaired hepatic function. Peak blood pressure decreases were greater in the cirrhotic group, which was in keeping with the higher plasma levels in these subjects. PMID- 2328555 TI - Human N-acetylation genotype determination with urinary caffeine metabolites. AB - The human acetylation genotype was determined by measuring urinary caffeine metabolites by use of a modification of a previously published HPLC method. The problem of separation of 7-methylxanthine (7X) from 1-methyluric acid (IU) in urine extracts was achieved by adding a phenyl column, in tandem with a C18 reverse-phase column, by means of a methanol:aqueous acetic acid gradient elution system. The urinary molar ratios of (AAMU)/(AAMU + 1U + 1X) and (AAMU)/(1X) were estimated in 20 subjects phenotyped with dapsone, with 100% concordance for the [AAMU]/[1X] ratio. A population study of 42 unrelated individuals exhibited trimodal distribution in acetylation capacity, consistent with the Hardy-Weinberg theory of population genetics. Definitive pedigree analysis of 16 families (75 subjects) resulted in significant similarity between the observed genotypic matings and those expected by classical Mendelian segregation. This noninvasive genotyping method promises to be useful in future investigation of the relationship between the human acetylation polymorphism and clinical disorders. PMID- 2328556 TI - Comparison of deferoxamine pharmacokinetics between asymptomatic thalassemic children and those exhibiting severe neurotoxicity. AB - The use of deferoxamine for iron chelation in transfusion-dependent thalassemia major is limited by serious neurotoxicity (hearing and vision loss). We assessed whether interpatient variability in handling deferoxamine and resultant accumulation of the drug may account for the neurotoxicity. We studied steady state deferoxamine pharmacokinetics during intravenous infusion in two groups of patients--one group exhibited severe manifestations of auditory and visual loss and one group was asymptomatic. The groups were matched for age, sex distribution, weight, treatment period, ferritin levels, and hemoglobin levels. Similarly, doses of deferoxamine at the time of the study were not different. Clearance rates were not different between the symptomatic and asymptomatic patients (39.83 +/- 4.54 versus 30.66 +/- 4.39 ml/min.kg). However, patients who exhibited toxicity received significantly higher daily doses of subcutaneous deferoxamine at the time of diagnosis of neurotoxicity (9.03 +/- 0.96 and 5.58 +/ 0.61 mg/kg.hr, respectively; p less than 0.005). These data suggest that deferoxamine induced neurotoxicity is dose-dependent and cannot be attributed to accumulation of the drug caused by slower clearance rates. PMID- 2328557 TI - Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers. AB - The effects of fluoxetine, a relatively selective long-acting serotonin uptake inhibitor, on the consumption of alcoholic and nonalcoholic drinks, cigarette smoking, and body weight were assessed in 29 men who were early stage problem drinkers. After a 2-week baseline, subjects were randomly assigned to receive 40 mg/day fluoxetine (n = 8), 60 mg/day fluoxetine (n = 11), or placebo (n = 10) for 4 weeks. Fluoxetine 60 mg/day decreased mean daily alcoholic drinks from (X +/- SEM) 8.3 +/- 0.7 during baseline to 6.9 +/- 0.7 and decreased total drinks per 14 days from 115.8 +/- 9.3 to 96.5 +/- 9.5 (p less than 0.01; 17.3% decrease from baseline), with no significant increase in days of abstinence. Neither 40 mg/day fluoxetine nor placebo had effects on intake of alcohol. Fluoxetine 60 mg/day decreased total and mean daily alcoholic drinks compared with 40 mg/day fluoxetine (ANCOVA, both p less than 0.02), but neither dose of fluoxetine was different from placebo. Compared with placebo, both 40 mg/day fluoxetine and 60 mg/day fluoxetine no differences were detected between treatment groups, 60 mg/day fluoxetine increased mean daily nonalcoholic beverages from baseline (5.0 +/- 0.4 to 5.6 +/- 0.3, p less than 0.01) and increased daily cigarettes smoked (from 25.1 +/- 4.6 to 26.9 +/- 4.5, p less than 0.05), whereas no significant changes from baseline were observed with 40 mg/day fluoxetine or placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328558 TI - Evaluation of analgesic agents in recurring headache compared with other clinical pain models. AB - The efficacy of three preparations (placebo, analgesic agent, and analgesic plus antihistaminic agent) were compared in a double-blind crossover study in subjects with recurring headaches. It was confirmed that headache as a pain model does not show the usual return of pain with as the effects of a single analgesic dose wear off. Consequently, there is no "peak effect," and the rationale for comparing treatments by "area under the curve" calculations is weakened. Greater efficacy was demonstrated for the analgesic over the placebo and for the analgesic and antihistaminic combined over the analgesic alone in several parameters. Slopes of straight lines derived as a quadratic function of pain versus time data proved to be a more effective discriminator between treatments than area under the curve calculations from the same data. PMID- 2328559 TI - Concentration-response relationship in imipramine treatment of diabetic neuropathy symptoms. AB - A single-blind imipramine dose titration study was conducted in 15 diabetic patients with neuropathy symptoms. The effect of treatment was evaluated by use of visual analog scales. Imipramine doses were individually adjusted until doses yielded plasma concentrations of imipramine plus desipramine that were well above 400 nmol/L or until all neuropathy symptoms had vanished. In all except one patient, there was marked relief of symptoms. In the responding patients (n = 14), much of the effect occurred at plasma levels of imipramine plus desipramine below 100 nmol/L, but a considerable interindividual variation was observed. Concentrations above 400 to 500 nmol/L were required to ensure maximal effect in all patients, and we did not find any indication of a decreased effect at high drug levels. The dose-dependent kinetics of imipramine was confirmed, and dose increments should therefore be carried out in small steps and preferably with monitoring of drug levels. PMID- 2328560 TI - Dose-dependent pharmacokinetics of caffeine in humans: relevance as a test of quantitative liver function. AB - Caffeine clearance was determined in 13 healthy control subjects and in 13 patients with histologically proven cirrhosis. On separate occasions, 70 mg, 200 mg, and 300 mg single doses of anhydrous caffeine were administered orally with decaffeinated coffee to each subject. Subjects were analyzed individually, acting as their own controls, thus reducing interindividual variability. The present study showed that caffeine exhibited dose-dependent pharmacokinetics, particularly in subjects who showed high initial clearance with the low dose (70 mg) of caffeine. There was a significant decrease in caffeine clearance with increasing dose from 70 mg to 300 mg (n = 26, p less than 0.01, Dunnett's test), indicating saturable caffeine metabolism in the dose range tested. These findings imply that if caffeine is to be used as a guide to deteriorating liver function, serial caffeine clearance estimations should be performed in each individual subject, with use of the same dose of caffeine each time. PMID- 2328561 TI - Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal. AB - Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours. PMID- 2328562 TI - Coadministration of naproxen and low-dose methotrexate in patients with rheumatoid arthritis. AB - Fifteen patients (30 to 78 years of age) with diagnoses of rheumatoid arthritis were administered oral and intravenous methotrexate (15 mg), alone or with concomitant naproxen (1000 mg/day). Serial blood samples and urine were collected for 24 hours after the dose of methotrexate and were assayed for methotrexate by a specific radioenzymatic method. In twelve patients who completed the study, methotrexate systemic clearance was not statistically different with naproxen (103.3 +/- 35.0 ml/min) versus without naproxen (113.4 +/- 48.3 ml/min; p = 0.37). Oral clearance of methotrexate was not statistically different with naproxen (161.7 +/- 55.0 ml/min) versus without naproxen (176.7 +/- 68.3 ml/min; p = 0.14). Likewise, there was not a significant difference in methotrexate renal clearance or plasma protein binding with or without naproxen. No toxicity was observed when patients received methotrexate alone or with naproxen. This study indicates that concomitant naproxen does not abruptly alter the disposition of low-dose methotrexate in patients with rheumatoid arthritis who have normal renal function. PMID- 2328563 TI - Automated record linkage. PMID- 2328564 TI - Aesthetic preference and syntactic prototypicality in music: 'tis the gift to be simple. AB - In the dominant aesthetic theory, composers are said to use unpredictable events to tease the listener, and make music optimally challenging and therefore aesthetically pleasing. We tested this claim that events optimally discrepant from a schema will be most pleasing. Experts and novices evaluated harmonic progressions at seven levels of syntactic prototypicality. Four results emerged: (1) even novices were extremely sensitive to syntactic atypicality; (2) all subjects found atypical progressions more interesting and complex; (3) novices and undergraduate music students preferred harmonic prototypes, contrary to most aesthetic theories; (4) only music graduate students preferred atypical progressions. We discuss the striking sensitivity of novices to harmonic syntax. We describe differences between an aesthetic theory based on information and uncertainty, and one based on schemas and schema divergence. We also consider the tonal conservatism of most subjects. This conservatism constrains aesthetic theories, and may have implications for music's stylistic evolution. PMID- 2328565 TI - Structural stability of fish myosin subfragment-1. AB - 1. Tryptic cleavage of fish myosin subfragment-1 (S-1) revealed its similar substructure of heavy chain to that of rabbit S-1. 2. The structural stability of fish S-1 was studied by thermal denaturation method, and a rapid polymerization of inactivated fish S-1, detected by turbidity increase, was characteristic. 3. The light-chain release and tryptic susceptibility increase upon heating were significant with fish S-1. PMID- 2328566 TI - Isolation of transferrin from porcine gastric mucosa: comparison with porcine serum transferrin. AB - 1. An iron-binding glycoprotein has been purified to homogeneity from porcine gastric mucosa. 2. The molecular weight (80,000), amino acid composition, carbohydrate content, N-terminal amino acid sequence, tryptic map, stoichiometry of iron binding (2 mol/mol), visible absorption spectrum of the ferric complex and chromatographic behaviour of the gastric protein are all strikingly similar to the corresponding properties of porcine serum transferrin. 3. The quantity of the gastric protein (1.3 mg/g wet weight) present in the gastric mucosa suggests that it is not serum transferrin (plasma concentration 1.8 mg/ml) contaminating the tissue. 4. A role for transferrin in the uptake of dietary iron by the gastrointestinal tract is proposed. PMID- 2328567 TI - A comparison of cardiac glutathione S-transferases from wild and domestic animals. AB - 1. Cardiac glutathione S-transferases from wild animals; hyena, red fox, porcupine, coypu and mountain gazelle were purified and compared with the enzymes from domestic animals; cow, camel, goat and sheep. 2. By using 1-chloro-2,4 dinitrobenzene as a substrate, domestic hearts expressed higher glutathione conjugating activity than wild animals hearts. 3. In all the studied hearts, the bulk of the activity was associated with near neutral and acidic glutathione S transferase isozymes with pI values ranging from 4 to 7.4. 4. The enzymes from domestic animals displayed homodimeric structure of 25,000 mol. wt subunit while of the wild animals both hyena and coypu displayed homodimers of 26,500 mol. wt subunit and the rest exhibited heterodimers of 25,000 and 28,000 mol. wt subunits. PMID- 2328568 TI - Variant surface glycoprotein of Trypanosoma brucei brucei AnTat 1.1: influence of the isolation conditions upon the disulfide linked dimer/monomer ratio. AB - 1. Using the variant surface glycoprotein (VSG) isolation procedure described by Baltz et al. ([1976] Ann. Immunol. (Inst. Pasteur) 127 C, 761-774) which involves suspension of the trypanosomes in a pH 5.5 buffer, the Antwerpen trypanozoon antigenic type (AnTat) 1.1 VSG is mainly obtained as a disulfide linked dimeric form with a trace amount of a monomeric form. 2. The use of a parasite suspension buffer at pH 7.0 results in a slight decrease of the VSG dimer/monomer ratio. 3. pH 5.5 and 7.0 supernatants of centrifuged parasite suspensions were submitted to kinetic incubations at different temperatures and pH, and we found conditions involving transformation of the AnTat 1.1 VSG dimer into the AnTat 1.1 VSG monomer (shifting the pH 5.5 supernatant to pH 7.0 and incubation at room temperature). 4. This transformation of the AnTat 1.1 VSG dimer into the AnTat 1.1 VSG monomer is activated by the addition of 1 mM reduced glutathione, and is inhibited by the addition of 1 mM oxidized glutathione or 0.1 mM N-ethylmaleimide or cadmium acetate. PMID- 2328569 TI - Distribution of delta-aminolevulinic acid synthetase and delta-aminolevulinic acid dehydratase in liver and kidney of rainbow trout (Salmo gairdnerii). AB - 1. Activities of delta-aminolevulinic acid synthetase (ALA-S) and delta aminolevulinic acid dehydratase (ALA-D) in trout liver and kidney were compared with those in the mouse. 2. ALA-S activity (per unit tissue fresh weight) exceeded ALA-D activity in trout liver and kidney. 3. In trout kidney, ALA-S activity slightly exceeded, and ALA-D activity far exceeded, their activities in trout liver. 4. In trout, heme synthesis differs from that in mammals in that appreciable synthesis occurs in the kidney, and in that ALA-S activity is not rate limiting. PMID- 2328570 TI - The hemoglobin of the aquatic snail, Planorbella duryi (Wetherby). AB - 1. The hemoglobin of the pond snail, Planorbella duryi has a molecular weight of 1.64 x 10(6) to 1.77 x 10(6) as determined by light-scattering at 630 nm and a sedimentation coefficient of 36 S. 2. The analysis of the circular dichroism spectrum obtained in the 190-250 nm region suggests a high degree of helical folding of the polypeptide chains of P. duryi hemoglobin analogous to human hemoglobin and myoglobin, with estimates of alpha-helical folding of about 60 65%, 0-5% beta-structure, and the remaining portion of the chains in unordered form. 3. The dissociated subunits in 6.0 M GdmCl, in the absence and in the presence of reducing reagent (0.1 M dithiothreitol), have a molecular weight of 3.73 +/- 0.23 x 10(5) and 1.93 +/- 0.04 x 10(5), suggesting a di-decameric assembly of the parent hemoglobin organized in the form of five dimers held together by disulfide-linkages. 4. The native hemoglobin is strongly resistant to both pH dissociation and dissociation by urea and such salts as NaCl and NaClO4. Dissociation and denaturation could only be effected in concentrated GdmCl solutions. 5. The influence of the various dissociating agents on the quaternary structure suggest ionic stabilization of the decameric assembly, which is stabilized by salt bridges between the subunits. PMID- 2328571 TI - Mapping of fish myosin light chains by two-dimensional gel electrophoresis. AB - 1. Myosins were prepared from the ordinary muscle of 16 fish species as well as from rabbit fast muscle, and light chain subunits [alkali light chains A1, A2 and DTNB (5,5'-dithio-bis-2-nitrobenzoate) light chain] were separated on two dimensional gel electrophoresis in combination with isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 2. A1 light chains showed mol. wts ranging from 21,000 to 22,900 and isoelectric points ranging from 4.51 to 4.62. DTNB light chains were spotted in a narrow area, with a mol. wt range of 16,800-17,600 and an isoelectric point range of 4.48-4.55. On the other hand, A2 light chains were most species-specific, with a mol. wt range of 14,000 19,500 and an isoelectric point range of 4.31-4.46. 3. It was suggested that the lower species-specificity in A1 as opposed to A2 is accounted for by the addition of an N-terminal peptide ("difference peptide") in the former. The properties and possible role of this peptide are discussed. PMID- 2328572 TI - Comparative studies on glutamate decarboxylase and choline acetyltransferase activities in the vertebrate vestibule. AB - 1. Vestibular putative neurotransmitters GABA and acetylcholine synthesizing enzymes were quantified in four vertebrate species to find a correlation between all-vertebrate vestibular hair cell II (HCII) and synaptic contacts and appearance of hair cell I (HCI) and related synapses in terrestrial species. 2. Glutamate decarboxylase (GAD) and choline acetyltransferase (ChAT) values were: 3.76; 15.38; 21.68; 27.78 and 9.44; 450; 720; 970 n(pico)mol/mg protein/hr (min) in, respectively, frogs, guinea pigs, rats and chicks. 3. GAD and ChAT omnipresence may indicate constant GABAergic HCII and its cholinergic efferent synapses, their raised content, appearance of GABA-containing HCI and related cholinergic boutons in higher vertebrates. PMID- 2328573 TI - Glycosidases in Brachionus plicatilis (Rotifera). AB - 1. Tests for glycosidases were performed in homogenates of Brachionus plicatilis. 2. Hydrolytic activity was detected with the following substrates: (a) with synthetic substrates (NP = 4-nitrophenyl): NP-alpha- and NP-beta-D glucopyranoside, NP-alpha- and NP-beta-D-galactopyranoside, NP-N-acetyl-beta-D glucosaminide, NP-N-acetyl-beta-D-galactosaminide, NP-alpha- and NP-beta-D mannopyranoside and NP-alpha-L-fucopyranoside; (b) with disaccharides: sucrose, maltose, trehalose, isomaltose, cellobiose, gentiobiose and lactose; (c) with polysaccharides: laminarine, carboxymethyl-cellulose, avicel, Micrococcus luteus (for lysozyme) and 4-nitrophenyl-alpha-D-maltoheptaoside (for amylase). 3. The pH dependence of the glycosidase activities was determined. 4. The distribution of enzyme activities within fractions from the homogenate was studied in order to localize them within the cell. 5. Proteins from Brachionus homogenate were separated by SDS-gel electrophoresis and the positions of the following glycosidase activities were detected by assays performed on the gels (estimated molecular weights in parentheses): alpha-glucosidase (250,000); beta-glucosidase (200,000); beta-galactosidase (70,000); N-acetyl-beta-glucosaminidase (60,000). PMID- 2328574 TI - Effects of estradiol-17 beta and estriol on their binding sites in the rabbit uterus. AB - 1. Receptors for estradiol-17 beta (E2) and estriol (E3) were detected in the rabbit uterus. 2. Saturation analysis of estrogen binding sites in the cytosol showed that the dissociation constants of E2 and E3 for the high affinity binding sites were 1.8 +/- 0.5 nM and 2.3 +/- 0.3 nM, respectively, when dextran-coated charcoal was used to isolate free and bound ligands. 3. To eliminate non-specific (cross) bindings to their receptors, effects of unlabeled E2 and E3 on [3H]E3 and [3H]E2 bindings was examined. 4. [3H]E2 cytosol binding was observed to be specific for E2 and [3H]E3 cytosol binding was more specific for E3. 5. E2 priming to rabbits increased the binding sites for both E2 and E3, which was also more potent than E3 priming. 6. Moreover, the increase in E2 binding sites was greater than that in E3 binding sites. 7. These findings may suggest that there are separate binding sites for E2 and E3 in rabbit uterus and that synthesis of their binding sites is regulated by E2 but not E3. PMID- 2328575 TI - MORFOREL, a computer program for two-dimensional analysis of micrographs of biological specimens, with emphasis on immunogold preparations. AB - The program is a tool for accelerating analysis of tissue components (profiles) as seen in micrographs, including electron micrographs with immunoreactive substances labelled with gold particles. Required equipment is a computer with digitizer and printer. From coordinates sampled around the profiles, area, perimeter and form factor are calculated; particles in profiles, when wanted, are counted to obtain particle densities. MORFOREL permits basic statistical calculations on primary data or on composite expressions based on them. Expressions can be saved on disk and retrieved. Primary and calculated data are readily output in a format readable by common commercial packages. PMID- 2328576 TI - Computer program for the reservoir model of metabolic crossroads. AB - A program containing 344 sentences, written in BASIC and adapted to run in personal computers (PC) has been developed to simulate the reservoir model of metabolic crossroads. The program draws the holes of the reservoir with shapes reflecting the Vmax, Km (S0.5) and cooperativity coefficients (n) of the enzymes and calculates both the actual velocities and the percentage of contribution of every enzyme to the overall removal of their common substrate. PMID- 2328577 TI - A computer model of re-entry in cardiac tissue. AB - This paper describes the use of a computer model to investigate the nature of impulse propagation and the mechanisms of electrical instability which precipitate ventricular arrhythmias. The model provides the opportunity for a systematic analysis of the conditions of cardiac conduction under controlled conditions. From the simulation studies performed it is found that the most critical parameter which influences re-entry circuit formation is the ratio of exited to refractory duration. PMID- 2328578 TI - Computer integrated measurement of respiratory compliance. AB - Respiratory compliance is obtained from the ratio of lung volume change to change in differential pressure across the chest wall, and is classically derived from the slope of the static, transrespiratory pressure-volume relationship. The need to remove subjectivity from the derivation of respiratory compliance, has prompted the development of a computer-based system which facilitates compliance measurement with minimal experimenter error. This paper outlines the basic algorithms necessary to analyse static, quasi-static and dynamic pressure-volume data, and describes how these data may be entered into a graphics package (Sigmaplot) to derive best-fit polynomial curves. PMID- 2328579 TI - Infectious crystalline keratopathy in a neonatal infant. AB - Bilateral white crystalline opacities of the central corneas were found at autopsy in the eyes of a 17-day-old girl with Turner's Syndrome. Corticosteroid therapy had not been used. Histopathologic and electron microscopic evaluation revealed clusters of gram-negative rods between relatively intact stromal lamellae. Inflammation was mild and restricted to the limbus and peripheral cornea. This case represents an unusual presentation of an infectious crystalline keratopathy. PMID- 2328580 TI - Abnormal extracellular matrix in corneas with pseudophakic bullous keratopathy. AB - The present study describes biochemical and morphological differences of pseudophakic bullous keratopathy (PBK) corneas as compared with normal corneas. At the ultrastructural level, all PBK corneas studied had abnormal fibrillar material posterior to the Descemet's membrane. In addition, two of the six PBK buttons had subepithelial fibrocellular materials disrupting the epithelial basement membrane and Bowman's layer. Aggregates of collagen fibrils with 110 nm periodicity were occasionally seen within the stroma of the PBK corneas. Isolation and purification of the collagen from the Descemet's membrane/posterior collagenous layer (DM/PCL) showed an increased amount of material with molecular weight in the range of 50-60K daltons (presumably type VIII collagen) and decreased amounts of higher molecular weight, disulfide-bonded collagenous materials (presumably type IV collagen) as compared with normals. Sugar-specific lectin studies showed an increased deposition of peanut agglutinin (PNA) and Ricinus communis agglutinin I (RCA120) in the DM/PCL of the PBK corneas. Our data suggest that the DM/PCL of PBK corneas have an increased accumulation of terminal B-galactose and B-D-galactose (1-3)-D-N-acetylgalactosamine residues and altered ratios of low and high molecular weight collagenous proteins. PMID- 2328581 TI - Acridine orange and Gram stains in infectious keratitis. AB - Two hundred thirty consecutive cases of presumed infectious keratitis were reviewed. Cultures were positive in 49.5% (114 of 230). Acridine orange stain sensitivity (81%) was significantly greater than gram stain sensitivity (65%) (p less than 0.002). Gram stain specificity was 92%, and acridine orange specificity was 89%. In keratitis with low or moderate growth, acridine orange was positive in 73% (61 of 84) as compared with Gram stain 53% (45 of 84), (p less than 0.001). In cases of heavy microbial growth, Gram stain was positive in 97% (29 of 30), acridine orange in 100% (30 of 30). This study demonstrates that both Gram stain and acridine orange stain are excellent in cases of infectious keratitis with heavy microbial growth, but that acridine orange is significantly better than Gram stain in cases with low amounts of organisms. PMID- 2328582 TI - Long-term follow-up study of scleroplasty using autogenous periosteum. AB - Autogenous periosteum was used to reinforce scleral thinning, perforation, or corneoscleral wound dehiscence in four eyes of three patients with necrotizing scleritis or peripheral ulcerative keratitis associated with advanced rheumatoid arthritis. All grafts have remained intact during an average follow-up interval of 36 months (range, 19-52 months). The postoperative visual acuity ranged between 20/30-20/60. Two eyes exhibited age-related macular degeneration, and one eye had an epiretinal membrane postoperatively. No systemic complications occurred following surgery. PMID- 2328583 TI - Anterior stromal micropuncture electron microscopic changes in the rabbit cornea. AB - Anterior stromal micropuncture has become an effective treatment for recurrent erosion. The healing process in rabbit corneas was investigated. Following micropuncture of the corneal surface with a 27-gauge needle knife, electron microscopy was carried out at regular intervals from time 0 through 5 months. The corneal incisions began to fill with epithelium by day 1. Activated keratocytes were adjacent to the basement membrane defect by 7 days. The basement membrane appeared to be healed at 2 and 4 weeks. Epithelial projections into the stromal incisions with underlying mature basement membrane persisted at 5 months postsurgery. Basement membrane reproduction occurred much more rapidly following needle puncture than after microdiathermy. This was thought to occur because the corneal epithelial cell was immediately exposed to type I collagen, whereas following microdiathermy, new type I collagen must be secreted on the necrotic collagen before the corneal epithelium will secrete basement membrane. PMID- 2328584 TI - Keratoconjunctivitis sicca and corneal ulcers. AB - We reviewed the records of 56 patients (109 eyes) who satisfied our criteria for keratoconjunctivitis sicca (KCS) to determine factors associated with the development of sterile corneal ulcers. The patient's age, sex, and associated local ocular surface and/or systemic disease were studied. We found a statistically significant association between the development of corneal ulceration and the presence of an underlying condition or disease state, especially chronic rheumatoid arthritis. Patient sex and age were not significantly associated with the development of corneal ulceration. We present three case histories that illustrate the complications that arise in managing KCS plus an associated disease and methods of management. PMID- 2328585 TI - Endogenous Listeria monocytogenes endophthalmitis presenting as keratouveitis. AB - We report a case of Listeria monocytogenes endophthalmitis that presented as a recalcitrant keratouveitis in a nonimmunocompromized patient. L. monocytogenes was recovered from the patient's aqueous, vitreous, and two of three blood cultures. He was treated with topical, subconjunctival, and systemic antibiotics, but the visual outcome was poor, possibly because of late diagnosis. A review of previous cases of L. monocytogenes endophthalmitis demonstrates unique features of this infection: (a) presentation as an anterior uveitis or keratouveitis with elevated intraocular pressure, (b) endogenous origin, and (c) frequent occurrence in nonimmunocompromized patients. PMID- 2328586 TI - Amantadine caused corneal edema. PMID- 2328587 TI - Corneal trauma and infection caused by manipulation of the eyelashes after application of mascara. PMID- 2328588 TI - Dellen or pseudodellen. PMID- 2328589 TI - Long-term changes in corneal endothelium after keratoplasty. A follow-up study. AB - In 1983, Abbott et al. assessed endothelial cell population and function in 100 clear corneal grafts (72 patients) that were an average of 17.4 years postkeratoplasty. The present study reports on 61 of these grafts (42 patients) followed for an additional 4-6 years. Forty-nine grafts without intercurrent complications or surgery were reexamined by specular microscopy to determine the change in endothelial population in each graft. In 10 others, the reasons for regrafting were recorded. In two cases of hereditary stromal dystrophy, stromal opacity precluded a cell count. Of the grafts studied, 49 (80%) remained clear despite a depleted and slowly decreasing endothelial population. The rate of change was independent of donor age, preoperative diagnosis, or graft longevity. Two grafts failed spontaneously, and all three grafts that had cataract surgery failed in the early postoperative period. The remaining five were regrafted to correct high astigmatism or other complications. We conclude that despite a small degree of continuous cell loss, corneal grafts have a favorable prognosis for long-term clinical stability. The remaining endothelium has a minimal functional reserve, however, resulting in a high risk of graft decompensation after additional endothelial trauma. PMID- 2328590 TI - Secondary localized amyloidosis of the cornea associated with tertiary syphilis. AB - Secondary corneal amyloidosis is a rare finding and only 17 cases have been reported in the literature. A case of unilateral secondary localized corneal amyloidosis is presented in a patient with bilateral interstitial keratitis and other stigmata of tertiary syphilis. PMID- 2328591 TI - Age, chronic disease, sepsis, organ system failure, and mortality in a medical intensive care unit. AB - We retrospectively studied relations between age, pre-existing chronic disease, sepsis, organ system failure, and mortality in 487 patients from a medical ICU. Single organ system failure (SOSF) occurred in 136 (28%) and multiple (greater than or equal to 2) organ system failure (MOSF) in 187 (38%) patients. Cardiovascular and pulmonary failure predominated. Overall mortality was 27%. SOSF mortality was 16% and for MOSF 58%. Eighty-three percent of nonsurvivors had MOSF. Hence, MOSF is common and a major cause of death in critically ill medical patients. Advancing age and prior chronic disease may diminish physiologic reserve and predispose to sepsis and MOSF. Although sepsis is a major risk factor for MOSF, a nonspecific host response to critical illness may contribute to the syndrome in 35% of patients. Advancing age, chronic disease, and the number of failing organs, particularly failure of cardiovascular, pulmonary, renal, and neurologic systems, are major determinants of overall mortality, but sepsis is not an independent contributor. PMID- 2328592 TI - Doppler ultrasound and clinical evaluation in detection and grading of patient ductus arteriosus in neonates. AB - The hemodynamics and patency of ductus arteriosus (PDA) in 51 infants were examined clinically and by echocardiography during the first or second day of life. Gestational ages ranged from 27 to 41 wk (34.0 +/- 3.6); birth weights ranged from 1070 to 4320 g (2256 +/- 923). Ductal flow was apparent by Doppler echocardiography in 24 of 51 infants but clinical examination disclosed only nine of these. Ultrasound is superior to clinical examination in diagnosing both symptomatic and asymptomatic PDA. Doppler ultrasound has the additional advantage of evaluating the size and relative importance of the ductal flow. PMID- 2328593 TI - Whole blood activated clotting time in infants during extracorporeal membrane oxygenation. AB - Bleeding complications are the principal cause of morbidity and mortality in infants treated with extracorporeal membrane oxygenation (ECMO). The whole blood activated clotting time (ACT) test is used universally to monitor heparin therapy during this procedure. To enhance our understanding of this test and improve our management of anticoagulation, we studied the relationship between the ACT and blood heparin concentration in nine infants during ECMO. The activated clotting time correlated with the simultaneously determined heparin concentration (r = .55, p less than .001 for all patients samples; r = .92, p less than .001 for mean patients values). Within the range of values found in our patients, platelet count, fibrinogen, and fibrin degradation products did not affect the ACT-heparin concentration relationship. However, the interpretation of an individual ACT result was limited by its low precision: the mean difference of duplicate determinations was 9.2%, and the estimation of heparin concentration by a single ACT had a coefficient of variation of 32%. Two commercially available techniques using different activators gave results that differed numerically but correlated well with each other. Both provided similar precision in the estimation of heparin concentration. The ACT is a low cost, bedside test whose accuracy and precision allow the achievement of target heparin concentrations required in infants during ECMO. Multiple determinations, either in duplicate or serially, are needed to achieve satisfactory precision. These data will be useful in designing future studies to determine the optimal serum heparin concentration to provide adequate anticoagulation, but avoid bleeding complications. PMID- 2328594 TI - Diaphragmatic flutter resulting in failure to wean from mechanical ventilator support after coronary artery bypass surgery. AB - Diaphragmatic dysfunction, most commonly elevation of the left hemidiaphragm and/or phrenic nerve paralysis, are well-known complications of coronary artery bypass grafting (CABG). Diaphragmatic flutter (DF) is an easily overlooked breathing pattern characterized by rapid (greater than 40 times/min) involuntary contractions of the diaphragm, at times superimposed on a more normal breathing pattern (dirhythmic breathing). Using respiratory inductive plethysmography, we were able to record this unusual ventilatory pattern in four patients after CABG. All procedures were performed via median sternotomy with topical hypothermia. Sternal complications were present in three cases (instability, dehiscence, infection). DF could not be suppressed by mechanical hyperventilation or patient volition. Weaning was unsuccessful until after DF abated. Diaphragmatic flutter may occur after CABG and should be considered as a cause of failure to wean from mechanical ventilator support in this setting. PMID- 2328595 TI - Level of nursing care required by the unstable angina patient. AB - To determine the nursing workload required for the unstable angina patient, we prospectively evaluated 116 consecutive patients admitted to the coronary care unit (CCU) with unstable angina. The level of nursing care was determined by the number of CCU complications and interventions. Patient acuities were ranked on a scale of I to IV using the Therapeutic Intervention Scoring System (TISS). The nursing workload was graded as follows: I = 0-9 points, II = 10-19 points, III = 20-29 points, IV = greater than or equal to 30 points. Points were determined by the quantity of life-threatening complications requiring nursing-assisted procedures for each patient during the CCU stay. Due to a low incidence of complications and need for interventions, the majority of unstable angina patients were in the acuity level I (78%). The CCU nursing workload for the unstable angina patients was moderately low. These data indicate that a significant percentage of unstable angina patients do not need therapy that requires a CCU setting. PMID- 2328596 TI - Effects of coenzyme Q10 in hemorrhagic shock. AB - We studied the effects of coenzyme Q10 (CoQ10) on pulmonary function and chemical mediators in a canine model of hemorrhagic shock. One group received 10 mg/kg of CoQ10 before hemorrhage. During the study, percent change from baseline of peak airway pressure, total lung compliance of the lung and chest wall, and blood lactate levels appeared to be significantly smaller in dogs pretreated with CoQ10 than in controls. Furthermore, CoQ10 was found to maintain blood histamine levels and to attenuate the increase in leukotriene C4. The mechanism of the beneficial effects of CoQ10 in hemorrhagic shock is presently unknown, but our data suggest that it may be useful in the treatment of hemorrhagic shock. PMID- 2328597 TI - Respiratory system mechanics in guinea pigs after acute hemorrhage: role of adrenergic stimulation. AB - We evaluated the effects of acute blood loss on the respiratory mechanics of guinea pigs. We measured respiratory system elastance (Ers) and resistance (Rrsmax) using the end-inflation occlusion method. Rrsmax was partitioned into its homogeneous component (Rrsmin) and that due to the unevenness within the respiratory system (Rrsu). Respiratory mechanics were studied both before and immediately after bleeding in eight animals. Another eight guinea pigs had received propranolol previously and were also submitted to hemorrhage. Propranolol-treated animals showed higher control values of Rrsmax (p less than .02) and Rrsmin (p less than .0001). Animals not treated with propranolol exhibited a decrease (p less than 0.001) in Rrsmax after hemorrhagic hypovolemia (from 0.375 +/- 0.051 to 0.323 +/- 0.042 cm H2O/ml.sec), due to a decrease (p less than 0.005) in Rrsmin (from 0.140 +/- 0.031 to 0.094 +/- 0.032 cm H2O/ml.sec), whereas Ers and Rrsu did not change. Propranolol-treated animals showed an increase (p less than .001) in Rrsmax (from 0.512 +/- 0.133 to 0.664 +/ 0.144 cm H2O/ml.sec), Rrsu (p less than 0.01) from 0.252 +/- 0.09 to 0.345 +/- 0.139 cm H2O/ml.sec, and Ers (p less than 0.001) (from 4.565 +/- 0.933 to 5.402 +/- 1.24 cm H2O/ml) after bleeding. The results indicate that the immediate effects of acute bleeding on respiratory mechanics are significantly influenced by catecholamines. PMID- 2328598 TI - Effects of dopexamine hydrochloride on hypoxic pulmonary vasoconstriction in isolated rat lung. AB - Dopexamine hydrochloride is a new analog of dopamine that lowers systemic vascular resistance and has positive inotropic and chronotropic properties, but lacks the alpha-adrenoceptor agonist activity of dopamine. The effects of dopexamine on hypoxic pulmonary vasoconstriction (HPV) are not known. We investigated this using an isolated, blood-perfused, and ventilated rat lung model. To study HPV, the ventilating gas was changed from an FIO2 of 0.21 to 0.03 and dopexamine hydrochloride was added. At blood concentrations of 100, 200, and 300 ng/ml, dopexamine caused a significant decrease in HPV of 22 +/- 3%, 31 +/- 4%, and 58 +/- 4% (mean +/- SEM, p less than .05), respectively. This effect was blocked completely by pretreatment of the preparation with propranolol (0.5 mg/kg, p less than .05). Dopexamine also induced significant (p less than .05) vasodilation of the pulmonary circulation preconstricted under normoxic conditions with prostaglandin F2 alpha, suggesting that the effects of the drug were not specific to hypoxia. We conclude that dopexamine inhibits HPV and vasodilates the pulmonary circulation by stimulation of beta 2 adrenoceptors. PMID- 2328599 TI - Acute histologic effects of simulated large-volume aspiration of sucralfate into the lungs of rats. AB - Sucralfate is an effective agent in reducing the incidence of upper GI tract (UGIT) stress bleeding and nosocomial pneumonia in critically ill patients. Many of these patients are not intubated and are at increased risk for aspiration of large volumes of UGIT contents containing sucralfate. The effects of aspirated sucralfate are unknown. To investigate this, large-volume aspiration (2 ml/kg) was simulated in freshly tracheostomized rats (n = 6, all experimental groups) using normal saline, particulate antacid, and sucralfate adjusted to pH 3.6 and 5.0. Four hours after aspiration, the rats were killed and their lungs were formalin-fixed. Significant increases in lung inflammation were seen by light microscopy in all experimental groups at pH 3.6. Antacid aspirated at pH 5.0 induced significant increases in airway as well as parenchymal inflammation. At pH 3.6, the antacid aspiration led to significant increases in lung edema and hemorrhage. Sucralfate aspiration produced significant increases in pulmonary hemorrhage at pH 5.0. Our microscopic findings are consistent with the acute pulmonary histopathologic changes known to occur after large-volume aspiration of particulate materials, including antacids. Additionally, we show that large volume aspiration of sucralfate produced significant acute pneumonitis, including pulmonary hemorrhage. In view of the proven usefulness of sucralfate, further investigations are indicated to evaluate these experimental findings before extrapolating to critically ill patients. PMID- 2328600 TI - Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats. AB - Bacterial translocation and ileal and cecal injury have been shown to occur 24 h after limited periods of hemorrhagic shock. The present studies were performed to determine the temporal sequence of mucosal injury, permeability, and bacterial translocation after hemorrhagic shock. The results indicated that bacterial translocation and mucosal injury have occurred by 2 h after a 30-min episode of shock (mean arterial pressure 30 mm Hg). Although the histologic extent of the intestinal mucosal injury was less at 2 h postshock than at 24 h postshock, at both times intestinal barrier function was lost as measured by permeability to horseradish peroxidase. Since the role of translocating bacteria in potentiating the loss of intestinal barrier function after shock is unclear, the second goal was to determine whether the extent of shock-induced mucosal injury and permeability could be reduced or abrogated by antibiotic decontamination of the gut. The extent of shock-induced mucosal injury and intestinal permeability was similar between rats with a normal gut flora (greater than 10(6) bacteria/g cecum) and antibiotic-decontaminated rats (less than 10(3) bacteria/g cecum) 2 h postshock, although the incidences of bacterial translocation were 67% and 0, respectively. Thus, shock-induced mucosal permeability and injury appear not to be directly related to the presence of translocating bacteria. PMID- 2328601 TI - Third-degree burns from the use of an external cardiac pacing device. AB - Noninvasive external cardiac pacing has been used safely in various cardiac emergencies for over 30 yr. Its use in neonates, however, has been associated recently with burns. We report the case of a 7-wk-old infant who sustained a full thickness burn after prolonged use of an external pacing device. PMID- 2328602 TI - Fulminant hepatic failure in poisoning due to ingestion of T 61, a veterinary euthanasia drug. AB - A patient developed fulminant hepatic failure 48 h after the ingestion of T 61, a veterinary euthanasia drug which contains both general and local anesthetics, a neuromuscular blocking agent, and dimethylformamide (DMF) as a solvent. This is the first report of such severe hepatic manifestation in T 61 poisoning, the most common symptoms of which are early coma and respiratory failure due to the anesthetic and the neuromuscular blocking agent. In a very few cases mild and transitory symptoms of hepatic insufficiency have been observed. In this case the fulminant hepatic failure was due to the high dose (0.6 ml/kg) ingestion of DMF. PMID- 2328603 TI - Airway obstruction caused by Aspergillus tracheobronchitis in an immunocompromised patient. PMID- 2328604 TI - Normal ventilation/perfusion lung scan in a patient with proven pulmonary embolus. PMID- 2328605 TI - Leaky gut hypothesis: a historical perspective. PMID- 2328606 TI - Importance of trigger sensitivity to ventilator response delay in advanced chronic obstructive pulmonary disease with respiratory failure. PMID- 2328607 TI - Hyperlactemia in patients undergoing continuous arteriovenous hemofiltration with dialysis. PMID- 2328608 TI - Discrepancy between finger and nasal pulse oximetry. PMID- 2328609 TI - A difficult task. PMID- 2328610 TI - Cardiac tamponade: diagnosis and emergency intervention. PMID- 2328611 TI - Nursing dynamics of pediatric intraaortic balloon pumping. AB - Care of the child on the IABP continues to be a challenging experience. Further advances in IABP technology will improve the rate of survival for children with complex congenital heart defects and other more complicated diagnoses. Likewise, this technology will enable critical care nurses to increase their expertise resulting in new gains in nursing knowledge. PMID- 2328613 TI - Sudden death: helping bereaved parents in the PICU. PMID- 2328612 TI - NEC: etiology, treatment, prevention, and nursing care. AB - NEC, a highly lethal disease that affects premature/compromised infants, is characterized by ischemic necrosis of the gastrointestinal tract. While risk factors can be identified, pathogenesis is uncertain. Protective factors in breast milk promote intestinal maturation and protect the newborn gut from pathologic penetration of macromolecules. Medical and surgical treatments have improved the prognosis of those diagnosed with NEC; however, prevention appears to be the most effective way to decrease mortality rates in the ever-increasing premature population. PMID- 2328614 TI - Child passenger safety in the car: are we involved enough? PMID- 2328615 TI - Administration of measles, mumps, and rubella virus vaccine (live) to egg allergic children. PMID- 2328616 TI - Update--sexually transmitted diseases. PMID- 2328617 TI - Bismuth. PMID- 2328618 TI - Generalized argyria. PMID- 2328619 TI - Nevus elasticus and lichen sclerosus et atrophicus on the vulva. AB - A sixty-seven-year-old woman had complained of vulvar pruritus and vaginal soreness for eight months. Clinical and histologic examination showed an admixture of two different entities: nevus elasticus and lichen sclerosus et atrophicus. PMID- 2328620 TI - The bedside laboratory. A critical step forward in ICU care. PMID- 2328621 TI - Bedside diagnostic testing. PMID- 2328622 TI - Evaluating STAT testing alternatives by calculating annual laboratory costs. PMID- 2328623 TI - Large-bowel cancer in the young: a national survival study. AB - Large-bowel cancer in young patients is reported to be a more aggressive and advanced disease at presentation and is believed to be associated with a relatively poor prognosis. Of 2420 patients registered in New Zealand (1968 to 1970), 131 were under 40 years of age and 2289 were over 40 years of age. The annual average incidence of treatable colorectal cancer in patients under 40 years of age was 2.36 per 100,000 and 82.93 in patients over 40 years of age. There were predominantly more females in both age groups with colonic tumors, 50:44 (female:male), and 759:652 (female:male). The rectal tumor male-to-female ratio of 1:0.68 in those over 40 years of age was reversed in those under 40 years of age (1:2.08). There was no significant difference in the subsite distribution of colorectal cancer between the two groups. There was a higher proportion of Stage 1 tumors in those under 40 years of age and a correspondingly higher proportion of Stage 2 tumors in those over 40 years of age. The overall crude and relative five-year survival rates for patients under 40 years of age were both 60 percent, whereas the crude rate for older patients was 42 percent, with a corresponding relative rate of 53 percent. Ten-year survival rates were generally higher in younger patients. From this study, there was no evidence to suggest that younger patients (less than 40 years old) with colorectal cancer had worse prognoses and did not survive as long as older patients (40 years and over). PMID- 2328624 TI - T-cell subpopulations and colorectal cancer. PMID- 2328625 TI - The role of azathioprine in the management of ulcerative colitis. AB - The use of azathioprine in ulcerative colitis is unclear. The authors present the details and outcome of 47 patients who received azathioprine for either a) severe, resistant disease otherwise requiring surgery (28 patients) or b) patients with steroid dependence who have been followed up for at least 12 months (19 patients). Duration of treatment ranged from one week to 66 months (median, 12 months). Of the patients in Group I, 13 (46 percent) achieved remission, 11 of whom had not relapsed during a median follow-up of 22 months (range, 12 to 58 months), and 15 underwent surgery one week to 12 months (median, five weeks) after commencing azathioprine. In Group II, steroids were withdrawn or reduced in 12 (63 percent) patients and three patients required colectomy. Side effects necessitating withdrawal of azathioprine occurred in 12 patients (hematologic effects, 6 patients; gastrointestinal effects, 4 patients; other effects, 2 patients). Two patients required a reduced dose of azathioprine because of leukopenia. The authors conclude that azathioprine is a valuable therapeutic option in selected patients with ulcerative colitis. PMID- 2328626 TI - Investigations of the muscular architecture of the rectosigmoid junction in humans. AB - The rectosigmoid junction, the segment of the gut where the colon merges with the rectum, has characteristic morphologic features and specific functional significance. The purpose of this study was to investigate the precise morphology of the musculature of this junction as a preliminary step toward closer study of its function and a better understanding of intestinal motility. To this end, the topographic relations of the rectosigmoid junction were investigated in specimens from 39 human cadavers. Although these relations varied, in all cases the rectosigmoid was located intraperitoneally and was distal to the promontory of the sacrum. Examination of muscle specimens under the dissecting microscope revealed conspicuous bands of longitudinal fibers, with curved interconnections between the longitudinal and circular muscle coats. The rectosigmoid junction is not a true sphincter, although in functional terms it can be regarded as such. PMID- 2328627 TI - Ileoanal anastomosis without covering ileostomy. AB - Ileoanal anastomosis is usually performed with covering ileostomy. This is primarily done because of fear of pelvic sepsis. Temporary ileostomy may, however, be a source of significant complications. The first 21 patients in the authors clinic were operated upon using covering loop ileostomy in ileoanal operations. These patients had no anastomotic or pouch complications, but there were complications, especially with the closure of the ileostomy. Therefore, a trial of one-stage operations in ileoanal anastomosis was started. Ileoanal anastomosis without ileostomy was performed on 25 consecutive patients. All the patients were operated upon for ulcerative colitis. There was one patient with pelvic abscess who needed diverting ileostomy. Thus, the early failure rate in patients operated upon without ileostomy was 4 percent. There were many other complications among these patients, but no other relaparotomy was needed. The complication rate was not different in patients operated upon without ileostomy compared with the authors first 21 patients operated upon with ileostomy (60 and 52 percent, respectively). Patients with one-stage operation needed a significantly shorter mean hospital stay than patients with two-stage operation (13.6 days and 25.3 days, respectively; P less than 0.001). The use of corticosteroids appears not to be a contraindication for one-stage operation, because there were significantly more patients using corticosteroids in the one stage group compared with the two-stage group (92 and 62 percent, respectively; P less than 0.05). PMID- 2328628 TI - Usefulness of performing colonoscopy one year after endoscopic polypectomy. AB - This retrospective study defines a population with neoplastic colonic polyps who have had colonoscopic polypectomy and, in follow-up within one year, a repeat colonoscopic evaluation. The population was broken down into two groups, one group that had polyps at the second examination and one group that did not. This study determined which factor(s) were significant among this population in distinguishing whether new polyps would be found at one year follow-up. The authors found that among the many variables studied, only polyp multiplicity was significant in predicting polyp recurrence. More than one polyp found at index colonoscopy led to a significant chance of having a new polyp after only one year. Also, it was demonstrated that these "new" polyps were unlikely to have been "missed" polyps from the initial colonoscopy. Because of the shifting location, smaller size, and fewer instances of histologic atypia in these polyps compared with those at index examination, the authors believe that polyps found after one year may be assumed to have arisen de novo. Finally, the authors show that a significant number of polyps occur beyond the reach of the flexible sigmoidoscope (approximately 60 cm). The authors recommend that patients who have polyps undergo a colonoscopic examination. When patients are re-evaluated after having colonoscopic neoplastic polypectomy, they should undergo repeat colonoscopy. PMID- 2328629 TI - Abdominoperineal resection for severe perianal Crohn's disease. AB - Despite the high incidence of involvement of the perianal region in Crohn's disease, excisional surgery seldom is required for perianal disease alone. Nine patients are presented who had severe perianal Crohn's disease, which eventually required abdominoperineal excision of the anorectum. In all nine patients, it was secondary manifestations of anal Crohn's disease that precipitated proctectomy, such as high fistulas, strictures, and rectovaginal fistulas. These secondary phenomena, especially fistulas caused by cavitating ulceration, become self perpetuating by the mechanical effect of feces being forced into the tract. During the same period, 17 patients required rectal excision by abdominoperineal resection, where perianal disease was incidental to severe colorectal disease. There is a tendency for excessive delay before advising surgery for severe perianal disease. An attempt should be made to identify patients with a poor prognosis to avoid unnecessarily prolonged morbidity. Assessment of the exact nature of the anal lesion and assessment of Crohn's disease activity are important in making this decision. PMID- 2328631 TI - Rectal mucosal electrosensory testing--evidence for a rectal sensory neuropathy in idiopathic constipation. AB - Rectal sensation is usually assessed using balloon distention. The authors describe a more precise technique that avoids the variables of balloon dynamics and rectal diameter and compliance. Using both methods, rectal sensation was assessed in 13 healthy control women and 26 women with severe idiopathic constipation. Balloon distention in the rectum revealed an elevated sensory threshold (16.9 +/- 4.4 vs. 30.4 +/- 3.1 ml air, controls vs. patients, P = 0.018) and volume required to elicit a call to stool (61.1 +/- 9.1 vs. 97.5 +/- 6.4, P = 0.003) in subjects with severe constipation. The maximum tolerated volume was similar in the two groups. Rectal mucosal electrosensitivity was then tested using a bipolar ring electrode supplying a constant current. This demonstrated an elevated sensory threshold in the constipated subjects (16.3 +/- 3.0 vs. 27.4 +/- 2.1 mAmps, P = 0.005). There was a significant correlation between the sensation thresholds for balloon distention and electrical stimulation for the entire subject group (r = 0.39, P = 0.01). Two other patients with severe constipation after suspected extrinsic nerve damage were also studied and demonstrated a markedly abnormal electrical sensory threshold. Electrical testing avoided the variables inherent in balloon distention and was well tolerated, accurately quantifiable, and reproducible. The raised threshold to electrosensory mucosal testing suggests the presence of a rectal sensory neuropathy in patients with severe idiopathic constipation. PMID- 2328630 TI - Improvement of anal sensation with preservation of the anal transition zone after ileoanal anastomosis for ulcerative colitis. AB - One of the most important considerations in restorative proctocolectomy for ulcerative colitis is postoperative continence. Preservation of the anal transition zone has been associated with improved results after this procedure in the pediatric age group. This study was carried out to determine the effect of preservation of the amal transition zone in adult patients undergoing restorative proctocolectomy, comparing a group of patients with the anal transition zone preserved with a group of patients with the anal transition zone removed. Physiologic testing demonstrated improved sensation in those patients with a preserved anal transition zone. Functional results were not significantly improved, although there was a trend toward improved continence and discrimination in those with the anal transition zone preserved. Although the results are early and are not conclusive from the clinical standpoint, they are certainly encouraging and may justify continued use of this technique. PMID- 2328632 TI - Cecocolic intussusception in multiple lymphomatous polyposis of the gastrointestinal tract. Report of a case. AB - A rare case of recurrent cecocolic intussusception in an adult patient with multiple lymphomatous polyposis of the gastrointestinal tract is presented. Clinical features, especially the difficulty in distinguishing this entity from adenomatous polyposis on colonoscopy, and histopathology are discussed. It is important that surgeons and colonoscopists be aware of this rare form of diffuse gastrointestinal lymphoma because of therapeutic implications. PMID- 2328633 TI - Perianal ulcer: an unusual presentation of Wegener's granulomatosis. Report of a case. AB - A 46-year-old man, without remarkable past medical history, had a perianal ulcer that appeared spontaneously two months before presentation. At admission, the ulcer was painless, measuring 4 to 5 cm in diameter and showing detachment and a slightly papillomatous aspect at the edge but without induration of the base. Microscopic examination revealed cutaneous ulceration with a well-developed inflammatory response, a few small vessels with intraluminal thrombosis or necrotizing walls, and isolated microscopic granulomata. No infectious disease was detected. The diagnosis of Wegener's granulomatosis was made six months later, when the disease was clinically evident in three principal sites: upper airways, lung, and kidney. At that time, serum antineutrophil cytoplasmic autoantibodies were detected with indirect immunofluorescence microscopy. There has been an excellent response to immunosuppressive therapy. Review of the literature revealed no similar reports. PMID- 2328634 TI - Physical examination of the anorectum: a systematic technique. AB - Advances in medical technology have enabled the colorectal specialist to use sophisticated methodology and precision instrumentation for diagnosing disease. However, one must not overlook the value of the thorough, systematically approached anorectal examination for initially identifying abnormalities. PMID- 2328635 TI - Definitive management of acute pilonidal abscess by loop diathermy excision. AB - A simple technique of definitive management of acute pilonidal abscess is described. The procedure consists of incision with drainage of pus followed by controlled excision of diseased tissue and lateral sinuses, using a loop diathermy. It allows one-stage definitive management of both acute pilonidal abscess and chronic pilonidal sinuses. PMID- 2328636 TI - Risk management commentary: nursing responsibility levels in SICU. PMID- 2328637 TI - Increasing clinical use of pulse oximetry. AB - Changing the system from measuring blood gases through invasive measures to using noninvasive pulse oximetry is a challenge in the Critical Care Unit where invasive techniques are taken for granted. The authors report a project that was successful in increasing the use of noninvasive monitoring techniques by critical care nurses in a Surgical Intensive Care Unit. This clinical project became an important aspect of incorporating the staff in a change to more extensive use of pulse oximetry. This study defines the change in nursing practice with the use of pulse oximetry. The authors discuss three areas: (1) demonstration of the correlation between O2Sat as measured by the pulse oximeter and arterial blood gas saturations; (2) introduction of the pulse oximeter as a reliable alternative to ABGs when monitoring oxygenation; and (3) the establishment of guidelines for using pulse oximetry within the clinical setting. PMID- 2328638 TI - Post-MI patients' perceptions of their learning needs. AB - As with other patients, those with myocardial infarction (MI) are experiencing ever-decreasing lengths of hospital stay. As critical care nurses, we must design and implement educational programs to meet these constraints. This investigator found risk factors, pathophysiology, and medications to be the high-priority education topics for these recovering MI patients. PMID- 2328639 TI - Cooperative education. An innovative recruitment technique. AB - In the effort to solve the problem of our own nursing shortage, we concluded that an innovative and creative method must be sought to satisfy both short-term and long-term staffing needs. Statistics pointed to the dwindling enrollment figures in nursing programs, the lack of interest in a nursing career among high school students, and the generally declining number of college-age students. Our strategy was to tap a few students from that evaporating pool by hiring student nurses on a part-time basis in their senior year, giving them academic guidance throughout their clinical experience, and allowing them an opportunity to view the working role of the critical care nurse. PMID- 2328640 TI - MRI detection of heart transplant rejection. PMID- 2328641 TI - Nurse develops high-school prevention program. PMID- 2328643 TI - Support group for patients with life-threatening arrhythmias. PMID- 2328642 TI - National panel studies approval process for AIDS & cancer drugs. PMID- 2328644 TI - Chest physiotherapy. Evaluating the effectiveness. AB - Alterations in respiratory patterns frequently accompany critical illness. At least two nursing diagnoses are used to identify these common pulmonary complications. Using these diagnoses, the nurse at the bedside is able to evaluate and adapt chest physiotherapy techniques to obtain the most effective results for each patient. PMID- 2328645 TI - Mid-arm circumference. Estimating patients' weight. AB - Calculation of drug dosages and intravenous fluids rates are often based on the patient's weight. However, in many critical care situations either time cannot be spared to weigh the patient or the equipment is too cumbersome to use. Too often the patient's weight is estimated by guessing. This article explores the development of a rapid, easy, portable, and objective method for estimating weight based on mid-arm circumference (MAC). PMID- 2328646 TI - Patients with ventricular assist devices. Nursing diagnoses. AB - The nursing diagnoses relative to the patient with a ventricular assist device require collaborative and preventative interventions, and thus present a tremendous but rewarding challenge. PMID- 2328647 TI - Hypoplastic left heart syndrome repair. Preventing complications. AB - Hypoplastic left heart syndrome presents a special challenge for the neonatal/pediatric critical care nurse. The nurse plays a vital role in preventing the complications that may arise from the syndrome itself or the surgical repair. Here, the authors describe how to prevent complications following first stage palliation of hypoplastic left heart syndrome. PMID- 2328648 TI - Nursing responsibility levels for cardiac surgical procedures. AB - Nursing liability is an issue discussed regularly by both critical care staff nurses and nursing managers. Questions frequently arise regarding practice within the "gray area" of critical care. The high level of patient acuity often necessitates an expanded nursing role. Specific practice issues within the controversial areas of cardiac surgical nursing are addressed in this article, with a discussion of the implications of performing care that may be outside the accepted standard of practice. PMID- 2328649 TI - Research and policy. PMID- 2328650 TI - Drug abuse strategies. PMID- 2328651 TI - [Use of psychotropic drugs and addiction: approaches to epidemiologic research]. AB - Although the phenomenon of drug abuse in France is well delimited, it constitutes a public health problem. The way it spreads is sometimes 'epidemic' in sub-groups especially exposed. The somtic or relational consequences are short-term and it concerns more and more adolescents or young adults. Two main research axes have been developed: studies in the general population, adolescents or adults, in order to know the general context of licit and illicit psychotropic use in France, and specific studies in detoxification centers in order to describe the characteristics of drug addicts and to evaluate their requirements. Results of some recent surveys can illustrate these axes. Total abstinence is exceptional. Psychotropic drug abuse is deeply established in traditional French social customs. Most subjects had a narrow relation with psychoactive drugs. The variety as well as quantity of products allow everyone to adopt a style of consumption. Globally, alcohol consumption has decreased. Moderate consumers seem to be those who especially confine their drinking to daily wine consumption. On the other hand, the consumption of aperitifs and other drinks in on the increase. The dissociation of alcohol consumption from meals enhances drunkness. Nicotine poisoning in men had a parallel evolution and has increased in women. Psychotropic drugs (tranquillizers and hypnotics) are specially used by aged women on medical prescription. For the study of drug abuse, data is collected in specialised centers and prisons regarding socio-demographic variables, intoxication profile and medical and social consequences. For both the general and addict population, epidemiological research, especially typological analysis, allows to identify some sub-groups at risk of drug addiction. PMID- 2328652 TI - Treatment outcome: a neglected area of drug abuse research. PMID- 2328653 TI - Science aid to policy dilemmas: implications of alcohol research to policy formulation in U.S.A. PMID- 2328654 TI - [Addiction and primary prevention]. AB - Primary prevention sensu strictiori of the abuse of and dependence on, drugs most not only reduce their availability but, more importantly, strive to prevent the development of a demand for them already at an early age. To this end, the factors arousing such demands must be known. Epidemiological research should elucidate the environmental and behavioural traits which may pre-dispose the young individual to turn to drugs, alcohol, violence, crime, or even suicide, i.e., the development of chemical dependence cannot be an isolated target of preventive activities. In fact, primary prevention which envisages specifically and exclusively the misuse of drugs is not realistic. Rather, the preventive efforts must address the totality of factors involved in the possible development of deviating behaviour and should operate within the framework and as an integral component of health education as a whole with the aim to enable the individual to lead a healthy life--physically, mentally, and socially. PMID- 2328655 TI - A plan aimed at the prevention and treatment of drug dependence. PMID- 2328656 TI - Impact of research on designing strategies for preventing and treating dependence on drugs and alcohol. PMID- 2328657 TI - Medico-legal aspects of treatment and prophylactic care of narcotic drug addicts. PMID- 2328658 TI - Political implications of scientific research in the field of drug abuse: the case of cannabis. PMID- 2328659 TI - Socio-cultural factors affecting drug addiction treatment in Italy (fear of treatment). PMID- 2328660 TI - Politicians and scientists in the combat against drug abuse. PMID- 2328661 TI - Opiate maintenance and abstinence--attitudes, treatment modalities and outcome. PMID- 2328662 TI - [Is simultaneous cholecystectomy and choledochal exploration obsolete?]. AB - Perioperative data on 284 patients who had simultaneously undergone cholecystectomy and surgical exploration of the bile duct were analysed. The procedures had been performed electively in 234 patients (145 females, 89 males; median age 61.5 [20-84] years). Freedom from stone was achieved in 96.2%; complication rate was 25.2% and death rate 2.6%. There was no death among patients without any or only one risk factor, while the morbidity rate for them was 18%. There were five deaths among 34 patients with four or more risk factors, and 13 (38.2%) had complications. Three of the patients who had died had been operated on because of septic, obstructive cholangitis with fever greater than 37.5 degrees C and bilirubin levels greater than 5 mg/dl. The operation was performed as an emergency in 50 patients (32 females, 18 males; median age 71.5 [24-93] years. 94% of them were free of stone afterwards; death rate was 10%, complication rate 44%. These data suggest that indications for the double surgical procedure in case of cholecysto-choledocholithiasis should be related to risk factors. In an emergency and in patients at risk, endoscopic papillotomy and stone extraction should precede cholecystectomy. But the one-time and thus definitive double surgical procedure remains the management of choice for patients with few or no risk factors. PMID- 2328663 TI - [The quality of life following esophagectomy. The results of a psychosocial study of 80 cancer patients]. AB - Of 235 patients who, between 1982 and 1988, had undergone an oesophagectomy for cancer of the oesophagus, 80 (64 men, 16 women; mean age 54.6 [39-67] years) were re-assessed for the quality of their life since surgery. Three standardized questionnaires were used ("general physical complaints" [PC], "satisfaction with life" [SL], "psychosocial stress" [PS]), plus data from a representative random group of the normal population (n = 1761; PC), a group of 48 healthy persons (SL) and a group of 788 cancer patients (PS) with different types of malignancy. The point score for PC was, as expected, significantly higher for the patients than the random controls (23.5 vs. 14.3; P less than 0.001), but was lower than that of cardiac (30.2) and psychiatric patients (30.0; P less than 0.001). As for quality of life, the postesophagectomy patients scored 68.17, compared with 56.75 (P less than 0.001) for the healthy controls. The main psychosocial stress was less in the areas of anxiety and depression than in a loss of social activity and impairment of physical capacity. PMID- 2328664 TI - [Vascular anomalies as the cause of recurrent intestinal hemorrhages]. AB - A 24-year-old patient suffered from acute intestinal haemorrhage three times within 10 years. After the last bleeding coloscopy demonstrated mesenterial varices in the terminal ileum and in the colon between the caecum and the left flexure. There were no signs of portal hypertension or obstruction of the superior mesenteric vein either by sonography or by angiography. Arteriovenous malformations of the vascular ectasia type were identified as other potential causes of haemorrhage when selective digital subtraction angiography of the superior mesenteric artery was performed segmentally in the proximal jejunum. Since the bleeding stopped spontaneously, no curative therapeutic consequences resulted from the combined vascular disorder. The patient was advised to submit to treatment immediately if bleeding recurred, to enable an angiography to be performed in the acute stage. PMID- 2328665 TI - [Dissections of the vertebral artery following cervical chiropractic manipulations]. AB - In a 37-year-old female patient complaining of increasing pain in the neck and occiput, chiropractic manipulations at the cervical vertebral column were associated with ischaemias of the brain stem presenting as vertigo, transient "locked-in" syndrome followed by vomiting, and sensorimotor hemiparesis. Digital subtraction angiography (DSA) revealed complete obstruction of the right and slight dissection of the left vertebral artery. The symptoms receded within a few days after heparinisation with 1000 IU/h intravenously. A 39-year-old female patient developed vertigo, nystagmus, tetraparesis and dysarthria two days after chiropractic intervention because of refractory pain in the neck and occiput. DSA showed embolism of the basilar artery and extensive dissections of the vertebral arteries. The basilar artery was completely recanalized after local intraarterial fibrinolysis with 50,000 IU urokinase. During the further course of treatment the symptoms receded under heparin and phenprocoumon over a period of 8 months, except for hemiparesis on the left side especially affecting the arm. Trivial traumas can result in dissections of the vertebral arteries. Severe neck pain is a frequent, typical early symptom. Hence, patients with cervical vertebral column syndromes should receive chiropractic treatment only after careful diagnosis. PMID- 2328666 TI - [The treatment of hairy nevi in newborn infants]. PMID- 2328667 TI - [Fructose and sorbitol malabsorption]. PMID- 2328668 TI - [Effects of nicotine on left ventricular diastolic function in patients with coronary disease. An echocardiographic study]. AB - Echocardiography was performed before and after inhalation of 0.9 mg nicotine in 21 patients (6 women and 15 men with a mean age of 51.8 [38-73] years). All of them had angiographically confirmed coronary heart disease (stenosis greater than 50%) and smoked 20-50 cigarettes daily for at least 5 years. In addition, left ventricular filling parameters were determined by transmitral pulsed Doppler ultrasonography. In this technique the flow profile across the mitral valve is divided into the passive, early diastolic inflow (E wave) phase and the active, late diastolic inflow phase caused by atrial contraction (A wave). Isovolumetric relaxation time was measured by simultaneous M-mode recordings over the aortic and mitral valves. The following significant changes were noted after the dose of nicotine (medians; one-sided Wilcoxon test; P less than 0.05): peak velocity of the E wave decreased from 43 to 34.4 cm/s; the ratio between A and E wave peak velocities increased from 1.02 to 1.37; the velocity/time integral of the E wave decreased from 4.77 to 3.57 cm; the ratio between the velocity/time integrals of the A and E waves rose from 0.66 to 1.15; isovolumetric relaxation time increased from 90 to 121 ms. - In cigarette smokers with coronary heart disease, acute administration of nicotine hence caused a decrease in early diastolic transmitral blood flow and an increase in isovolumetric relaxation time. These changes point to significant impairment of left ventricular diastolic function. PMID- 2328669 TI - [Cardiac side effects of 5-fluorouracil]. AB - In four patients (a 54-year-old man and three women aged 57, 60 and 65 years, respectively) with colorectal carcinoma and no obvious cardiac abnormality anginal symptoms and ECG changes occurred during chemotherapy with 5-fluorouracil at a dose of 400 and 600 mg/m2. The ECG changes consisted of descending ST depressions with preterminally negative T waves, terminally negative T waves, ventricular extrasystoles and sinus tachycardia with intermittent atrial fibrillation. The signs first appeared between the second and fourth day of treatment; in two patients they improved with glyceryl trinitrate. A few days after 5-fluorouracil had last been administered all ECG changes had disappeared. The causes of cardiotoxicity of the drug remain unknown. PMID- 2328670 TI - [Congenital aneurysm of the membranous interventricular septum]. AB - In a 50-year-old patient with complex ventricular arrhythmia (monotopic ventricular extrasystoles in bigeminy and triplet form), coronary angiography with ventriculography revealed an aneurysm of about 2-3 cm diameter that bulged visibly into the right ventricle during the systole. Electrophysiology was able to localise the earliest excitation during the ventricular extrasystoles at the septal border of the aneurysm. Hence, the congenital aneurysm was definitely identified as the source of the arrhythmia. Surgery or drug therapy were not indicated since there was no haemodynamically effective ventricular tachycardia in the patient who was largely free from complaints. PMID- 2328671 TI - [Arteriosclerosis without risk factors?]. PMID- 2328672 TI - ["Lost" bile duct drain--nevertheless not lost]. PMID- 2328673 TI - [After night shift]. PMID- 2328674 TI - [Infections caused by Mycobacterium avium complex in patients without predisposing factors]. PMID- 2328675 TI - [Doctor's-office blood pressure, home blood pressure, ergometry blood pressure and 24-hour blood pressure. The correlations with the echocardiographic parameters of heart muscle mass]. AB - In 62 untreated hypertensives (31 men, 31 women; median age 40 [17-57] years) blood pressures (BP) were measured in the doctor's office, at home (self measured) and every 15 min during 24-hour monitoring (by portable automated oscillometry), the results being compared with echocardiographic measurements of ventricular septal thickness (VST), left ventricular muscle mass (LVM) and left ventricular mass index (LVMI), in 41 of them also during and 5 min after 100 W bicycle ergometry. In the total cohort, 24-hour values correlated better with diastolic VST (systolic: r = 0.706, P less than 0.00001; diastolic: r = 0.507, P less than 0.0001) than office BP (systolic: r = 0.381, P less than 0.01; diastolic: r = 0.177, not significant) and home BP (systolic: r = 0.477, P less than 0.0001; diastolic: r = 0.371, P less than 0.05). In the 41 exercised hypertensives the correlation with echocardiographic values was less close than with their 24-hour BP, but slightly better than with office and home BP. Systolic BP correlated better than diastolic BP with echocardiographic values. VST generally correlated better with BP than LVM and LVMI. It is concluded that (1) 24-hour BP values correlate more closely with LVM than any other noninvasive BP measurement; (2) VST is affected more by systolic than diastolic BP; and (3) VST more specifically reflects the influence of BP on myocardial structure than does LVM and LVMI. PMID- 2328676 TI - [The retrograde endoscopically implantable, self-expanding endoprosthesis (stent) in malignant choledochal stenoses]. AB - Self-expanding, wire-mesh stents, 10 mm in diameter, were implanted retrogradely through the papilla of Vater via an endoscopically introduced catheter system in 14 patients (9 females, 5 males, mean age 70.2 [44-85] years) with stenosis of the common bile duct by malignant tumour. Postimplantation examinations revealed no complications caused by the stent. Two of the patients have since died from their underlying disease, the others have survived an average of 10.8 weeks with markedly reduced clinical symptoms, neither jaundice nor signs of cholestasis having recurred. Serum bilirubin concentration had fallen from a mean of 8.2 mg/dl to 1.7 mg/dl 12 weeks after the procedure. Serum alkaline phosphatase activity had similarly fallen, from 515 to 330 U/l. No increase in serum amylase activity was recorded, either initially or in the course of follow-up. PMID- 2328677 TI - [Generalized argyrosis]. AB - For many years a 52-year-old patient suffering from duodenal ulcer had taken a silver-containing preparation, the total quantity of silver ingested in this manner amounting to about 35 g. 18 years after the first manifestation of duodenal ulcer a dermatologist diagnosed argyria and confirmed this by biopsy. After acute coronary failure with marked nicotine abuse autopsy revealed granulated deposits of silver in the corium, particularly on elastic fibres, at the sweat glands, sebaceous glands and hair follicles. There were no deposits in the epidermis. Dense silver deposits were also seen in the walls of most of the blood vessels, in the basal membranes of the renal glomeruli, of the choroid plexus and of the seminiferous tubules, as well as in the portal fields. Definite intracellular deposits occurred in macrophages only. The metal was found only rarely in epithelial basal membranes. Generalised argyria does not entail any pathological implications and is considered to be intractable. PMID- 2328678 TI - [Nonstenosing arterial calcinosis]. PMID- 2328679 TI - [Addison's disease in pregnancy]. PMID- 2328680 TI - [Cerebral functional disorders after mountain climbing at extreme altitudes]. PMID- 2328681 TI - [Biological and behavioral rhythms of patients with schizophrenia. Preliminary study]. AB - Relying on the ethological model for the collection of data (ethogram), psycholinguistic methods (Cloze procedure, type token ratio) and chronobiological techniques, the present study tests the hypothesis of behavioural, speech and biological ultradian or circadian rhythms in certain types of schizophrenic patients after a 2 week study. Six daily, direct and meticulous 25 minutes observations of the behaviour and speech of four schizophrenics show that stereotyped motor or verbal behaviour does not always fluctuate at random; certain behavioural patterns recur regularly at fixed intervals, according to a set time structure. Most of the behavioural, verbal and biological variables have their acrophase at 10 a.m. and/or at 4 p.m. Instability in the rhythm of the sleep/wake cycle and the oral temperature observed in schizophrenics could be the result of desynchronization of the central pacemakers or of the resynchronization, or even of hypersynchronization with a delay of one phase. It is difficult to ascribe this desynchronization to the illness or the treatment. PMID- 2328682 TI - [Diagnostic criteria of depressive pseudodementia]. AB - Ten patients fulfilling the DSM III (A, B, C, D) criteria for both dementia and major depression and presenting the diagnostic dilemma of depressive pseudodementia were included in a prospective study in search of indices for the differential diagnosis of depressive pseudodementia (DPSD) and organic dementia (OD). Patients were assessed with the Hamilton Depression Rating Scale (HDRS), the Blessed Dementia Rating Scale (BDRS), the Wells's criteria, the Mini Mental State (MMS), computerized tomography (CT scan) of the brain, the dexamethasone suppression test (DST), total plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and sleep electroencephalograms (EEG). Patients suffering from DPSD were defined as showing an improvement higher than 50% in both the HDRS et BDRS scores following adequate antidepressant treatment. Wells's criteria, MMS scores, CT scan and DST do not contribute to the separation of DPSD (n = 6) and OD (n = 4). On the contrary, plasma MHPG levels higher than 35 ng/ml and EEG measures of sleep structure and REM sleep significantly differentiate the two groups. PMID- 2328683 TI - [Plasma levels of metapramine and its 3 major metabolites in patients with depression. Results and preliminary interpretations]. AB - Metapramine (Timaxel) and his three major metabolites (19148 RP, 23669 RP, 19749 RP) have been determined in the plasma of 18 depressed inpatients treated by the antidepressant drug (12 women and 6 men; 7 are smokers and 11 non-smokers). In a steady state, interindividual variability is very important, especially for 23669 RP. No significant correlation exists between normalized doses (mg.kg-1) and normalized plasma concentrations (ng.ml-1/dose mg.kg-1) of metapramine or anyone of its metabolites. The plasma metabolic ratios reveal also important intraindividual and interindividual variability. Two populations of patients seem to exist: extensive metabolizers and relatively poor metabolizers, without apparent clinical consequence because 23669 RP shows an antidepressant activity. Women seem, with equal normalized doses, to exhibit higher plasma levels of unchanged metapramine than men, due to a lower protein-binding rather than to a more active metabolism. In patients who received a poly-medication smoking seems not to induce desmethylation of metapramine. The plasma metabolic ratios, compared by the analysis of variance and the Wilcoxon distribution-free test, are significatively influenced by sex and not by tobacco-smoking. PMID- 2328684 TI - [A case of amineptine dependence]. AB - We relate a case of amineptine (Survector) dependence in a patient with a previous history of amphetamine dependence. Under pressure from the family, she came to the hospital with anxiety symptoms which had appeared 48 hours after suspension of the treatment. The product was initially prescribed by a psychiatrist three years previously and she took a dose of 100 mg/day for three months. Approximately one year ago she re-started the treatment on her own initiative, increasing the dose to about 30 tablets/day (3 g) in order to combat against asthenia and to be able to maintain her normal level of activity. In her history we find an episode of amphetamine dependence at 17 years old. We compare the characteristics of this case with other reported cases. Finally some recommendations for a better use of this antidepressant in similar cases are suggested. PMID- 2328685 TI - [Carpipramine]. PMID- 2328686 TI - NIH funding for biomedical research, 1990: perceptions and realities. PMID- 2328687 TI - Evidence for a role of the liver in the mammotrophic action of prolactin. AB - The possibility that the liver plays a role in the growth-promoting actions of PRL on the mammary lobuloalveolar (L-A) system was investigated using 6-week-old female rats. Chronic indwelling catheters were inserted into the external jugular vein (EJV) or the hepatic portal vein (HPV) and attached to osmotic minipumps, which were used to infuse pulses of ovine (o) PRL (4/day of 2 h each, total dose = 20 micrograms/day) for 14 days. The rats were hypophysectomized 2 days after catheterization, and given daily sc injections of estradiol + progesterone in oil (2 micrograms and 5 mg/day, respectively) plus twice daily ip injections of porcine GH (50 micrograms/injection) from days 2-13. They were killed on day 14. Controls received the sc and ip hormone injections but were given solvent infusion into the EJV or the HPV instead of oPRL. Infusion of the oPRL into the EJV did not promote mammary L-A growth more than did infusion of solvent into either the EJV or the HPV. By contrast, infusion of the same dose of the hormone into the HPV caused a significant stimulation of the L-A growth. Serum insulin like growth factor-I (IGF-I) levels were measured by RIA in the rats given the same hormone injections with either intrahepatic infusion of solvent or oPRL, but terminated 7 days after the start of infusion. Intrahepatic delivery of oPRL was not more effective at elevating serum IGF-I concentrations than was the infusion of solvent. These results indicate that the liver may participate in the mammotrophic actions of PRL and serum IGF-I is not responsible for this effect. PMID- 2328688 TI - Stimulation of growth hormone and prolactin release from rat pituitary cell aggregates by bombesin- and ranatensin-like peptides is potentiated by estradiol, 5 alpha-dihydrotestosterone, and dexamethasone. AB - The effect of the bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin-C (NMC), and the ranatensin-like peptides, neuromedin-B (NMB), neuromedin-B30 (NMB30), and neuromedin-B32 (NMB32), on pituitary GH and PRL release was studied in perifused anterior pituitary aggregate cell cultures from 9- to 12-week-old male rats cultured in serum-free defined medium supplemented with 0.05 nM T3 and 4 nM dexamethasone (DEX). All peptides stimulated PRL and GH release. GRP and NMC stimulated hormone release in a concentration-dependent manner between 0.1-10 nM. NMB was slightly more potent than NMB30 and NMB32, but was significantly less potent than GRP and NMC. The magnitude of the PRL response to GRP and NMC inversely correlated with that of the GH response. Cultures with relatively low PRL response levels displayed high GH responses, whereas the opposite was found in cultures with high PRL response levels. The stimulatory actions of GRP, NMC, and NMB were blocked by the bombesin receptor antagonist Leu13 psi (CH2NH) Leu14-bombesin, supporting the specificity of the findings. Addition of 1 nM estradiol (E2) to the culture medium provoked an impressive (4- to 10-fold) increase in the magnitude of the GH response to NMC without changing the EC50 value (0.5 nM). In contrast, E2 significantly decreased the stimulation of GH release by rat GH-releasing factor. In the E2-treated aggregates 3 nM NMC stimulated GH release to a comparable extent as 0.1 nM GRF. 5 alpha Dihydrotesterone (10 and 100 nM) and DEX (80 nM) also enhanced the GH response to NMC, but to a much smaller extent than E2. E2 had also a stimulatory effect on the PRL response to NMC, particularly in cultures with a low intrinsic PRL response. The PRL response to NMC was decreased by DEX and slightly augmented by 5 alpha-dihydrotestosterone. It is concluded that bombesin- and ranatensin-like peptides have a stimulatory effect on GH and PRL release at the pituitary level. Since their action on GH release is strongly potentiated by E2 and much less so by glucocorticoids, these peptides clearly distinguish their activity and specificity from that of the protagonist releasing factor GH-releasing factor, suggesting a role in sex-related differences in GH release or in the control of GH secretion during sexual maturation. PMID- 2328689 TI - L-triiodothyronine (T3) regulates cellular growth rate, growth hormone production, and levels of nuclear T3 receptors via distinct dose-response ranges in cultured GC cells. AB - Cultured rat somatotrophic cells have been useful models for the study of thyroid hormone action. A consensus of previous reports has indicated that approximately 0.2 nM T3 results in 50% occupancy of T3 nuclear receptors as well as half maximal stimulation of several T3 responses. To characterize the nature of thyroid hormone responses in GC cells, we studied in detail the T3 dose relationships between nuclear receptor occupancy and three thyroid hormone responses (cell growth, GH production, and T3 nuclear receptor regulation). The dose response to T3 for each parameter was unique, and none was identical to the dose response for receptor occupancy. Respective T3 concentrations and percentage of T3 nuclear receptor occupancy resulting in 50% of the maximal response for GC cell growth were 0.05 +/- 0.02 nM and 15 +/- 3% (four experiments), 0.15 +/- 0.04 nM and 27 +/- 3% for GH production (three experiments), and 2.1 nM and 69% for down-regulation of T3 nuclear receptors (two experiments). We conclude that the dose response for occupancy of the T3 nuclear receptor covers a wide range of T3 concentrations. Within the wide dose-response range for nuclear occupancy a spectrum of biological responses are regulated by distinct thyroid hormone dose ranges. These data suggest that the impact of T3 nuclear receptor occupancy on T3 responses might be variable and that the mechanisms involved may be clarified through studies in GC cells. PMID- 2328690 TI - Effects of oxytocin on in vitro steroid release of midstage small and large porcine luteal cells. AB - Previously, we have demonstrated an inhibitory effect of oxytocin (OXT) on progesterone (P) and androstenedione (A) release of porcine luteal cell cultures. The present study examines whether OXT modulates P, A, or estradiol (E2) release of so-called small luteal cells (SLC) or of granulosa-derived large luteal cells (LLC). To ensure clean Percoll-gradient separation of the 2 cell types, corpora lutea not older than 6 days were used. SLC, but not LLC, responded to human (h)CG (6 ng/ml) with increased P and A, but not E2, release. When OXT was added to the culture system, both basal as well as hCG-stimulated P release of SLC, but not of LLC, were dose dependently reduced. In contrast, E2 production of SLC and LLC was significantly stimulated by OXT whereas A release of SLC cultures, but not of LLC, was inhibited in response to OXT. In the presence of a specific OXT antagonist, this inhibitory effect of OXT on P release was abolished, indicating a specific receptor-mediated effect of OXT on porcine luteal cells. When E2 was added to the culture medium, a dose-dependent stimulatory effect on P release of SLC was demonstrated. The presence of the E2 receptor antagonist monohydroxy tamoxifen in the culture system prevented the E2-induced increase of P release of SLC. E2 was able to counteract dose dependently the OXT-induced inhibition of P release in SLC cultures. These results suggest that OXT may have a dual function in young corpora lutea. The reduction of P and A production can be interpreted as a luteolytic effect of OXT. The simultaneous increase of E2 production, however, may also point to an indirect luteotropic effect since E2 was shown to stimulate luteal P release and to counteract OXT-induced inhibition of P release excessively. PMID- 2328691 TI - Release and effects of oxytocin on estradiol and progesterone secretion in porcine corpora lutea as measured by an in vivo microdialysis system. AB - Individual corpora lutea (CL) of Gottinger miniature pigs were implanted with an in vivo microdialysis system. This system functions like an artificial capillary, allowing diffusion of intraluteally secreted substances into the lumen of the dialysis system and administration of hormones into individual CL and simultaneous measurement of the response. After surgery the sows are fully awake and unrestrained. In the present study the in vivo release rates and secretion dynamics of progesterone (P) and oxytocin (OXT) were investigated. The dialysis system was implanted at day 2-4 of the estrous cycle, and dialysis experiments were performed throughout the next 3 days. Fractions were collected at 30 min intervals, and the concentrations of P and OXT were measured by RIA. Three major observations were made: Spontaneous intraluteal secretion of P and OXT occurred in a pulsatile manner. OXT secretion episodes in individual CL often coincide, indicating a simultaneous release from many CL of one ovary but also from the CL located in the contralateral ovary. OXT episodes also often coincide with P pulses; statistical evaluation revealed a significant correlation between P and OXT secretion. Intraluteal application of OXT stimulated luteal P and estradiol (E2) release in a dose-dependent manner. E2 added to the perfusates was also stimulatory to P release. The stimulation of P release by OXT could be antagonized by prior treatment of the CL with tamoxifen. We demonstrate for the first time in vivo the secretion of OXT from porcine CL. The microdialysis system enabled us to collect samples at the site of steroid and peptide release, i.e. within the intact luteal tissue. Our results suggest a stimulatory effect of OXT on P release from young and middle-aged CL and are in marked contrast to the previously demonstrated inhibitory effect of OXT on P release when luteal cells were cultured in vitro. A possible explanation for this apparent discrepancy is that OXT stimulates intraluteal release of E2, which is a powerful P releasing hormone, overcoming the direct inhibitory effect of OXT. This suggestion is substantiated by the observation that E2, when added to the perfusion medium, indeed stimulated P release. PMID- 2328692 TI - Estrogen binding is a noncooperative process in primary rat uterine cells. AB - Estrogen binding in a primary rat uterine cell culture system did not exhibit positive cooperativity as judged by Hill coefficients. Under defined culture conditions, total specific [3H]estradiol (E2) binding in intact cells attained apparent equilibrium within 3 h after E2 had been varied from 5 to 250 pM. Thereafter, at each concentration of E2 studied, estrogen receptor (ER) levels were constant for up to 6 additional h. We have characterized a single high affinity E2 binding site with a dissociation constant (Kd alpha) of 0.01-0.05 nM E2. The binding capacity of the alpha-site is approximately 5-8 fmol/micrograms DNA, corresponding to approximately 20,000 receptors per cell. In extensive studies, we have seen no evidence for positive cooperative E2 binding. The Hill coefficient was never significantly (95% confidence level) greater than 1. Data are also presented which indicate that [3H]E2 exogenously added to the extracellular medium is in simple equilibrium with the intracellular compartment and the ER. When saturation analyses were conducted using medium that contained BSA, increased concentration of serum protein increased the apparent Kd of E2 for the receptor. No effect was observed on either the shapes of the binding curves or on the calculated Hill coefficients. Furthermore, dose correlations between E2 binding and stimulated response(s) indicated that the ER in these cells was biologically active, which was a major advantage of this culture system over freshly dispersed cells or cytosolic extracts. PMID- 2328693 TI - The methyltrienolone binding protein of human placenta requires nicotinamide adenine dinucleotide cofactor(s) for steroid binding. AB - The methyltrienolone binding protein (MTBP) found in human placental cytosol was found to require a low molecular weight modulator for steroid binding activity. Purification and characterization of the modulating activity showed that NAD+ is the endogenous substance responsible for activating MTBP to a form capable of steroid binding. The hierarchy of potency of exogenously added nucleotides is NADH greater than NAD+ = NADPH = NADP+. An investigation of the tissue distribution of human MTBP demonstrated that MTBP binding activity was present in placenta and chorion but absent from amnion and umbilical cord. Preliminary studies showed that rat, mouse, and rabbit placenta do not contain MTBP and suggest that MTBP may be a species-specific protein. PMID- 2328694 TI - Relaxin gene expression in the sow corpus luteum during the cycle, pregnancy, and lactation. AB - Relaxin (RLX) mRNA was sought in the corpus luteum of the pig during the cycle, pregnancy, and lactation using Northern analysis and in situ hybridization. Three oligonucleotide probes to regions of the preprorelaxin molecule were used for hybridization to detect RLX message and gave similar results. Northern analysis showed a single 1-kilobase RLX transcript at all three stages of the reproductive cycle studied. The intensity of the RLX hybridization signal was greatest in pregnancy and varied during the cycle. The signal in ovaries from day 3 cyclic animals increased by day 13 and declined on day 19. However, the hybridization signal at midcycle was only 2% of that during pregnancy. After parturition on day 2 of lactation, RLX message was still detected in the ovary, although at reduced levels compared with those during the cycle and pregnancy. In situ hybridization results showed hybridization to RLX mRNA in luteal tissue on day 13 of the cycle, but not on day 3 or 19. An increased hybridization signal was observed on days 40, 60, and 90 of pregnancy, with a decline on day 2 of lactation. Control sections incubated with labeled heterologous probe or preincubated with excess unlabeled probe did not hybridize. These results indicate a good correlation between the relative concentrations of RLX transcript and immunohistochemical results previously reported in the corpus luteum of the sow. In addition, they demonstrate that the RLX gene is expressed in luteal tissue, not only in pregnancy, but also in the cycle and early lactation. PMID- 2328695 TI - Ontogenesis of the nuclear 3,5,3'-triiodothyronine receptor in the rat testis. AB - The aim of this study was to investigate the ontogenesis of the nuclear T3 receptor among the different cell types in the rat testis from fetuses at the 19th day of gestation and animals 1, 5, 15, 20, and 60 days after birth. Whole testis, tubular fraction, nontubular fractions, and Sertoli cells cultured in vitro or enriched in vivo by irradiation were used. The results demonstrate that high affinity, low capacity T3-binding sites are localized only in Sertoli cells; the binding specificity and affinity (Kd ranges from 0.8 +/- 0.2 to 2.6 +/- 0.4 nM) do not change significantly with the age of the animals and are comparable to those observed for T3 receptors in other mammalian tissues. In the whole testis, the concentration of receptors changes during gonadal development, being maximally expressed in the fetus (154.3 +/- 8.1 fg T3 bound/10(6) nuclei) and from 1 (203.4 +/- 10.9 fg T3 bound/10(6) nuclei) to 5 (185.3 +/- 15.1 fg T3 bound/10(6) nuclei) days of postnatal life, decreasing significantly at 15 and 20 days (65.4 +/- 2.0 and 57.9 +/- 1.9 fg T3 bound/10(6) nuclei, respectively) and being virtually absent in the adult. The same change in receptor concentration was found in Sertoli cells obtained by different techniques. This ontogenetic profile coincides with the pattern of Sertoli cell proliferation and differentiation, thus suggesting a role of thyroid hormones in the regulation of growth and maturation of the somatic cells of the seminiferous epithelium. PMID- 2328696 TI - Prolactin response to immobilization stress and hemorrhage: the effect of hypothalamic deafferentations and posterior pituitary denervation. AB - The roles of posterior and anterolateral connections to the mediobasal hypothalamus (MBH) as well as innervation of the posterior pituitary in the PRL response to immobilization (IMO) and hemorrhage (HEM) were studied by means of surgical isolation, performed 6-9 days before stress exposure. Male rats bearing indwelling tail artery cannulae subjected to 120-min IMO reached peak PRL secretion in 5-20 min. HEM of 25% elicited a significant rise of PRL levels. A posterior cut in the MBH, performed without damaging the serotonergic fibers from the brain stem, attenuated the PRL response to 25% HEM, whereas the PRL elevation due to IMO remained unaffected. An anterolateral cut around the MBH eliminated both the IMO- and HEM-induced stimulation of PRL. Posterior lobe denervation reduced by about 27% the PRL response to IMO and eliminated the response to HEM. These results suggest the following conclusions. The neural structures located posteriorly to the MBH are involved in the transfer of signals triggering PRL secretion due to hypovolemia. Intact anterolateral pathways to the MBH and stalk median eminence region are essential for the PRL-releasing activity under both stimuli. The posterior lobe may be an important link in the PRL stress response in male rats. PMID- 2328697 TI - Inhibition of 5'-deiodination of thyroxine suppresses the cold-induced increase in brown adipose tissue messenger ribonucleic acid for mitochondrial uncoupling protein without influencing lipoprotein lipase activity. AB - Young adult male and female Djungarian hamsters were exposed to ambient temperatures of 23 or 0 C for 12 h; half of the animals in each group were treated with iopanoic acid to suppress the peripheral conversion of T4 to the thermotropically active thyroid hormone T3 by the enzyme 5'-deiodinase (5'D). Brown adipose tissue (BAT) mRNA for uncoupling protein (UCP), BAT lipoprotein lipase (LPL) activity, and 5'D activity were measured at the conclusion of the study. A temperature of 0 C produced large rises in 5'D and LPL activities and a similar large increase in UCP mRNA within the 12-h exposure period. When 5'D activity was inhibited with iopanoic acid, mRNA for UCP was reduced, while LPL activity was unaffected. The results show that the optimal production of mRNA for BAT UCP depends on the availability of T3; however, T3 is not required for the cold-induced activation of LPL activity in BAT. PMID- 2328698 TI - De novo synthesis and secretion of prolactin-like protein-B by rat placental explants. AB - Mid- to late-gestation rat placenta expresses three PRL-related mRNAs, rat placental lactogen-II (rPL-II), rat PRL-like protein-A (rPLP-A), and rat PRL-like protein-B (rPLP-B). The protein product of rPL-II mRNA has been characterized, and the protein products of the rPLP-A mRNA were recently identified. The mol wt of a nonsecreted nonglycosylated rPLP-B protein would be 27,145 based on the mRNA sequence. The present study is the first to report the identification of the rPLP B protein. Antiserum was generated against a chemically synthesized oligopeptide inferred from a specific region of the rPLP-B cDNA. Three or four distinct proteins synthesized and secreted by rat basal zone explants (day 15 gestation) showed cross-reactivity with the rPLP-B antiserum. The relative mol wt of these immunoreactive proteins is approximately 30,000, with a pI varying from 6.1-6.6. De novo synthesized rPLP-B proteins were not secreted by the explant tissue in the presence of tunicamycin, suggesting that the proteins are glycosylated. These data are consistent with the presence of one potential N-glycosylation site derived from the rPLP-B mRNA sequence. The rPLP-B antiserum showed no cross reactivity with proteins identified using antisera against rPLP-A, rPL-II, or human pregnancy-specific beta 1-glycoprotein. Immunocytochemical studies were carried out using paraffin sections from placentas of day 14 and 17 pregnant rats which were treated with anti-rPLP-B, followed by avidin-biotin-peroxidase complex. These experiments show perinuclear staining, which was localized in basophilic cytotrophoblast cells, confirming previous in situ mRNA hybridization studies. Although no physiological role has been established for rPLP-B, the synthesis and secretion of this protein by cells in contact only with maternal circulation suggest a hormonal role. PMID- 2328699 TI - Strain differences in the ontogeny of estrogen receptors in murine uterine epithelium. AB - The expression of estrogen receptor (ER) in the reproductive tracts of neonatal mice was examined using immunocytochemical and autoradiographic methods. Two strains of mice used in previous studies that reported contradictory results showed different rates of uterine epithelial development. In the inbred strain, BALB/c, the epithelium was devoid of receptor from birth through 5 days of age, while uterine epithelial cells of the outbred strain, CD-1, expressed ER as early as 3 days of age. Oviductal epithelium and cervical epithelium expressed ER on the day of birth in CD-1 mice. Glandular ontogeny in the uteri of CD-1 animals was also advanced by 3 days compared to that of BALB/c mice. These observations reconcile the conflicting reports of ER ontogeny in the neonatal mouse. More importantly, these results confirm our earlier observations, indicating that the cells lining uteri of 2- and 4-day-old BALB/c mice lack ER at a time when estrogen induces their proliferation. PMID- 2328700 TI - Regulation of iodothyronine 5'-deiodinases: effects of thiol blockers and altered substrate levels in vivo and in vitro. AB - To study the physiological regulation of the iodothyronine 5'-deiodinases (I 5'D), we have examined the effects of some thiol blockers and of thyroid status on I-5'D activities both in vitro and in vivo. At low (less than 5 mM) concentrations of dithiothreitol, propylthiouracil (PTU) inhibited I-5'D in the brain, pituitary, and brown adipose tissue (BAT) of hypothyroid rats (which contain predominantly the type II activity); the patterns of inhibition in these tissues were essentially similar, with a Ki of about 174 microM at 250 microM dithiothreitol. Hydroxyethyldisulfide was a strong inhibitor of the type II enzyme, with relatively little effect on the renal enzyme at both high concentrations (micromolar) of T4, i.e. predominantly type I activity, and low concentrations (nanomolar) to T4, i.e. both type I and low Km activity. Preincubation of cerebral microsomes with PTU, followed by removal of excess PTU, resulted in 70% inhibition of I-5'D activity in cerebral microsomes at 5 mM dithiothreitol; the corresponding inhibitions of the renal enzyme at high and low substrate concentrations were 66% and 48%, respectively. Specific binding of PTU to renal and cerebral microsomes was diminished by hydroxyethyldisulfide, but not by T4, suggesting that PTU binding was not dependent on substrate interaction. Administration of PTU in vivo (1 mg/100 g BW, ip; 1 h before killing) resulted in approximately 80% inhibition of I-5'D activity in renal microsomes at high T4, and 50-70% inhibition in pituitary, BAT, and renal microsomes at low T4, but no inhibition was observed in brain microsomes. HPLC analyses revealed a PTU content of 35-65 nmol/g wet wt in the pituitary, BAT, liver, and kidney, but no PTU was detected in the brain, suggesting that PTU may be excluded by the blood-brain barrier. Maintaining hypothyroid rats on 1 microgram T4/100 g BW.day for 5 days enhanced renal type I and low Km I-5'D with restoration of serum T3 to normal levels, although the type II I-5'Ds from all sources were severely depressed. A supraphysiological dose of T4 depressed all three I-5'Ds. The data indicate that the I-5'Ds are regulated in a qualitatively similar fashion. PMID- 2328701 TI - Regenerating marrow induces systemic increase in osteo- and chondrogenesis. AB - Marrow ablation in long bones induces an increase in osteogenesis in distant skeletal sites. To test the role of marrow regeneration in this phenomenon, rat mandibular condyles were evaluated histomorphometrically during postablation healing of tibial marrow and after inhibition of healing. Ten days after removal of tibial marrow all bone formation parameters in the condylar subchondral bone were markedly elevated, indicating an enhanced osteoblastic activity. The thickness of the cartilaginous zone of calcification was also augmented. These changes were absent when postablation healing was inhibited in the tibia and after massive liver injury. Extensive periosteal injury induced only a slight increase in osteoblast activity. Except for a fall on day 7, the [methyl 3H]thymidine labeling index in the condylar cartilage and oral mucosa remained at control levels 3-18 days after ablation. These findings imply that stimulation of cell proliferation has only a secondary role in the skeletal response to marrow ablation. It is concluded that the systemic increase in osteogenesis occurs preferentially during marrow regeneration and is not a nonspecific skeletal reaction to tissue injury. Apparently, the systemic osteogenic response is mediated by circulating factors produced by the healing marrow; conceptually it is related to other instances where local repair in extraskeletal sites is accompanied by generalized alterations in respective tissues. PMID- 2328702 TI - Two-dimensional gel autoradiographic analyses of the effects of 1,25 dihydroxycholecalciferol on protein synthesis in clonal rat osteosarcoma cells. AB - The steady state synthesis of L-[35S]methionine-radiolabeled cellular proteins by two rat osteogenic sarcoma cell lines (G2 and C12) was examined by two dimensional polyacrylamide gel electrophoresis under basal conditions and after 72-h treatments with 10 nM 1,25-dihydroxycholecalciferol or triamcinolone acetonide. Computer analysis resolved 681 spots, with mol wt ranging from 10-105K and isoelectric points ranging from 4.0-8.0. Fourteen spots were abundant (greater than or equal to 2000 parts/million), with the remainder occurring in limited abundance (150-2000 parts/million) in both clones. Only 28 proteins were radiolabeled at significantly different rates by G2 and C12 cells under basal conditions. The high degree of similarity in the identity and relative abundance of proteins synthesized by these distinct subclones suggests that minor changes in the levels of specific intracellular proteins may have major effects on the osteoblastic phenotype. 1,25-Dihydroxycholecalciferol [1,25-(OH)2D3] or triamcinolone acetonide treatment induced qualitative and quantitative changes in the synthesis of specific subsets of proteins, including induction of novel proteins, complete repression of proteins synthesized under basal conditions, and significant increases or decreases in the levels of others. 1,25-(OH)2D3 significantly altered the levels of 13 proteins in G2 cells and 28 proteins in C12 cells. 1,25-(OH)2D3 enhanced the synthesis of two proteins (no. 304 and 2506) in both subclones. The remainder of the proteins affected by 1,25-(OH)2D3 were unique to the subclone. With the exception of protein 304, the changes induced by 1,25-(OH)2D3 differed from those induced by triamcinolone acetonide, suggesting that unique proteins modulate the osteoblastic phenotype in response to these steroids. PMID- 2328703 TI - Calcium is the first messenger for the action of thyroid hormone at the level of the plasma membrane: first evidence for an acute effect of thyroid hormone on calcium uptake in the heart. AB - The thyroid hormone T3 produced a very rapid and transient increase in 45calcium uptake by freshly isolated rat heart slices, which was seen already 15 sec after the addition of the hormone, reached a maximum at 30 sec, and then progressively declined and returned to control values after 10 min. This effect of T3 was independent of extracellular calcium, concentration related (evident at a physiological concentration of 10 pM, reached maximum of about 75% above control at 1 nM, and was smaller at greater concentrations), and thyroid hormone specific, as judged from the order of potency of several thyroid hormone analogs: L-T3 greater than L-T4 greater than or equal to D-T3 greater than 3'-isopropyl 3,5-L-diiodothyronine greater than D-T4 greater than 3,5-L-diiodothyronine greater than r-L-T3 greater than D,L-thyronine. The inorganic calcium channel blockers La3+, Cd2+, and Mn2+ inhibited, in a concentration-related fashion, basal and T3-induced increases in 45Ca uptake in the cardiac slices. The organic calcium channel blockers verapamil, nifedipine, and diltiazem were without effect, indicating that in the quiescent cardiac slice the effect of T3 on 45Ca uptake is independent of sarcolemmal depolarization. Additional studies demonstrated that the stimulatory effect of T3 on 2-deoxyglucose uptake by the cardiac slices required extracellular calcium and was inhibited by the calcium channel blockers La3+, Cd2+, and Mn2+. The present study provides conclusive evidence for two central issues: that calcium is the first messenger for the prompt, plasma membrane-mediated action of thyroid hormone to increase cellular sugar uptake, and that thyroid hormone produces an acute increase in calcium uptake by the heart, an effect that is demonstrable at physiological concentrations and is thyroid hormone specific and, therefore, points to a physiological relevance for this action. PMID- 2328704 TI - Regulation of 11 beta-hydroxysteroid dehydrogenase activity in the baboon placenta by estrogen. AB - We have previously shown that the change in transuteroplacental cortisol (F) cortisone (E) metabolism in vivo from preferential reduction (E to F) at midgestation to oxidation by term (F to E) does not occur in baboons in which the production or action of estrogen have been blocked. Moreover, because the administration of androstenedione (delta 4A) to baboons increased estradiol (E2) production at midgestation and induced a pattern of F-E metabolism similar to that at term, we suggested that estrogen regulates placental F-E interconversion. The present study was designed to ascertain whether estrogen regulates the activity of the placental 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) enzyme catalyzing the oxidation of F to E. Placentas were obtained on day 100 (n = 10) and day 165 (n = 10) of gestation (term = day 184) from untreated baboons, on day 100 from animals (n = 7) treated with delta 4A between days 70-100 of gestation, and on day 165 from animals in which placental estrogen was decreased by fetectomy (n = 5) on day 100 of gestation. Tissue was homogenized in phosphate buffer (pH 7.4) and microsomal fractions (105,000 x g) incubated (37 C; 2 min) in buffer containing 2.7 mM NAD+ and 0.03-1.0 microM [3H]F. Serum concentrations of E2 (nanograms per ml) in untreated baboons on day 100 (0.7 +/- 0.2) were 3-fold lower than those at term, increased (P less than 0.05) by delta 4A treatment (2.4 +/- 0.3), and decreased (0.12 +/- 0.01; P less than 0.05) by fetectomy. The specific activity (picomoles of E per min/mg protein) of placental 11 beta HSD in untreated baboons at midgestation (134 +/- 17) was increased (P less than 0.01) 3 fold by delta 4A treatment. Enzyme activity at term (148 +/- 29) was similar to that at midgestation, but markedly decreased (P less than 0.01) by fetectomy (16 +/- 4). Placental capacity to oxidize F to E (micromoles per min/placenta) in untreated baboons was 3-fold greater (P less than 0.01) at term (88 +/- 15) than at midgestation and was markedly reduced (P less than 0.01) by fetectomy (3 +/- 1). Collectively, these findings indicate that the activity of the placental 11 beta HSD enzyme catalyzing the oxidation of F to E is increased in baboons in which placental estrogen production was elevated at midgestation and decreased in animals when estrogen formation was inhibited by fetectomy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2328705 TI - Analysis of the action of angiotensin II on the baroreflex control of heart rate in conscious rabbits. AB - There is considerable evidence that angiotensin II (Ang II) attenuates the baroreflex control of heart rate (HR), but the mechanism and site of this action have not been precisely defined. In the present study the effects of systemically and centrally administered Ang II on the baroreflex control of HR were investigated in conscious, chronically prepared rabbits. Baroreflex curves (HR vs. mean arterial pressure) were generated with iv infusions of phenylephrine or nitroprusside. Background infusion of Ang II at 10 ng/kg.min increased mean arterial pressure from 77.3 +/- 3.0 to 94.3 +/- 4.1 mm Hg (P less than 0.001) without changing HR [212.1 +/- 7.2 to 218.0 +/- 9.8 beats/min (bpm)] and shifted (reset) the baroreflex curve with phenylephrine to a higher pressure level (P less than 0.001) without changing its slope (-1.40 +/- 0.40 to -1.65 +/- 0.46 bpm/mm Hg; P = 0.4). Background infusion of an equipressor dose of phenylephrine did not shift the baroreflex curve or change its slope. Ang II also shifted the baroreflex curve with nitroprusside to a higher pressure level (P less than 0.01), but again the slope was not significantly changed (-2.30 +/- 1.25 to -1.51 +/- 0.52 bpm/mm Hg; P = 0.2). Background intraventricular infusion of Ang II at 1 ng/kg.min had the same effects as iv infusion of Ang II at 10 ng/kg.min; the curve was shifted to a higher pressure level (P less than 0.001), but the slope was not changed (-0.76 +/- 0.47 to -1.143 +/- 0.48 bpm/mm Hg). Intravenous infusion of Ang II at 1 ng/kg.min had no effect on the baroreflex. The resetting of the baroreflex with phenylephrine by iv Ang II (10 ng/kg.min) was not blocked by propranolol: atropine markedly reduced the baroreflex response to phenylephrine in both the absence and presence of Ang II. These results indicate that in conscious rabbits, Ang II resets the baroreflex control of HR, but does not change its sensitivity. This effect apparently results from an action of Ang II on the brain that is mediated by withdrawal of vagal tone to the heart. The resetting of the baroreflex by Ang II can explain the ability of the peptide to increase arterial pressure without decreasing HR. PMID- 2328706 TI - Contribution of maternal thyroxine to fetal thyroxine pools in normal rats near term. AB - Normal dams were equilibrated isotopically with [125I]T4 infused from 11 to 21 days of gestation, at which time maternal and fetal extrathyroidal tissues were obtained to determine their [125I]T4 and T4 contents. The specific activity of the [125I]T4 in the fetal tissues was lower than in maternal T4 pools. The extent of this change allows evaluation of the net contribution of maternal T4 to the fetal extrathyroidal T4 pools. At 21 days of gestation, near term, this represents 17.5 +/- 0.9% of the T4 in fetal tissues, a value considerably higher than previously calculated. The methodological approach was validated in dams given a goitrogen to block fetal thyroid function. The specific activities of the [125I]T4 in maternal and fetal T4 pools were then similar, confirming that in cases of fetal thyroid impairment the T4 in fetal tissues is determined by the maternal contribution. Thus, previous statements that in normal conditions fetal thyroid economy near term is totally independent of maternal thyroid status ought to be reconsidered. PMID- 2328707 TI - Ovarian oxytocin and neurophysin concentrations in the cynomolgus monkey (Macaca fascicularis). AB - The neurohypophysial hormone oxytocin has previously been found in the ovaries of several animal species. In ruminants ovarian oxytocin is postulated to have a luteolytic function, because of its high concentrations in the corpus luteum. In primates the role of ovarian oxytocin is not known. In the present study we measured the immunoreactive oxytocin and oxytocin-neurophysin content in paired ovaries removed from cynomolgus monkeys (Macaca fascicularis) during the late luteal phase of the cycle (Days 12-14 of the luteal phase or Days 26-28 of a menstrual cycle). Each animal was pulsed with synthetic gonadotropin-releasing hormone to maintain normal menstrual cyclicity. The concentration of oxytocin and its neurophysin during the late luteal phase was greater in the non-corpus luteum than corpus luteum-bearing ovary. By high pressure liquid chromatography and bioassay the oxytocin in both the corpus luteal and non-corpus luteal ovaries was similar to synthetic and posterior pituitary oxytocin. The finding of high concentrations of immunoreactive oxytocin in the non-corpus luteum-bearing ovary suggests that the function of ovarian oxytocin in primates may not be confined specifically to the corpus luteum. PMID- 2328708 TI - Effects of angiotensin-II on inositol phosphate accumulation and calcium influx in bovine adrenal and Y-1 tumor adrenal cells. AB - The present study compared the action of angiotensin II (A-II) in bovine adrenal fasciculata cells (BA) and Y-1 adrenal tumor cells which are sensitive and resistant respectively to its steroidogenic effect. In both models, A-II induced a time and dose-dependent inositol phosphate (Ins-Ps) accumulation and calcium influx. However, in Y-1 cells the Ins-Ps production was low and only Ins-P1 and Ins-P2 were accumulated. The calcium influx in BA cells was observed after 15 seconds and remained linear as long as the hormone was present, whereas in Y-1 cells calcium influx started prior to 15 seconds and reverted to basal values after 45 seconds. The effects of A-II on both cell types were specific since they were blocked by A-II antagonists. Taken together these results demonstrate the presence of functional A-II receptors in both cell types which are coupled to the two main intracellular messenger systems. Thus, the A-II steroidogenic refractoriness of Y-1 cells is probably related to some alteration(s) located beyond the calcium and/or protein kinase C A-II-messenger system. PMID- 2328709 TI - Studies of the potential role of a semisynthetic surfactant preparation in an experimental aspiration trauma in rabbits. AB - The intratracheal administration of 2 mL of betaine hydrochloride-pepsin mixture (pH 1.78) per kilogram body weight in healthy rabbits leads to severe impairment of lung mechanics. This deterioration becomes significant after 6, 24, and 48 h for the parameters of static compliance and the difference in volume between 0 and 20 mmHg airway pressure. This model was used to investigate the efficacy of a surfactant preparation consisting of a combination of synthetic phospholipids and natural surface-active rabbit material containing the protein fraction. This mixture has been shown be superior to the single components alone with regard to their behavior in vitro in a Wilhelmy balance after extensive cycling. This preparation was able to reverse the deterioration of lung mechanics when applied 24 h after an aspiration injury. Instillation of Ringer's solution alone did not show any therapeutic effect. This aspiration injury model may be helpful in further studies of therapeutic effects of surfactant preparations designed on the basis of the preparations' properties in vitro as preselective criteria. PMID- 2328710 TI - Effect of quinacrine on lipid content of bronchoalveolar lavage fluid in guinea pigs sensitized to ovalbumin. AB - In both ovalbumin-sensitized and ovalbumin-challenged guinea pigs, the phospholipid content of bronchoalveolar lavage fluid is decreased with respect to that of controls. In the sensitized guinea pig, the activity of lung membrane phospholipase is increased and the phospholipid content of lung membranes is decreased. In determining whether alveolar phospholipids are metabolized in a similar way, quinacrine, a phospholipase A2 inhibitor, was administered (10 mg/kg intravenously) to control, sensitized, and challenged animals before inhalation of ovalbumin. Pulmonary ventilation and lung mechanics were measured both before and after the injection of quinacrine and inhalation of ovalbumin. Phospholipid content was measured in the bronchoalveolar lavage fluid. In the control and sensitized groups quinacrine had no effect on pulmonary ventilation and lung mechanics, and in the challenged group it reduced the intensity of anaphylactic bronchospasm. In control animals it did not change the phospholipid content, whereas in the sensitized and challenged animals it suppressed the decrease of phospholipid content. The results suggest that in the sensitized and challenged guinea pigs alveolar phospholipids are degraded by phospholipase A2, the activity of which is increased. PMID- 2328711 TI - Cumulative effects of repeated surfactant treatments in the rabbit. AB - The responses of the adult rabbit lung to multiple doses of surfactant after intratracheal injections of either natural calf surfactant or Surfactant-TA were evaluated. For each surfactant, four groups of 1.4-kg rabbits were studied: group 1 received 100 mg of surfactant containing isotopically-labeled dipalmitoylphosphatidylcholine; group 2 received the same labeled surfactant and then three tracheal injections of vehicle; group 3 received labeled surfactant and then three doses (100 mg) of unlabeled surfactant; group 4 was treated in the same way as group 3 except that the final dose was of the labeled surfactant. All rabbits were killed, and alveolar washes were recovered 24 h after the labeled surfactant dose had been given. The amount of labeled palmitate-saturated phosphatidylcholine (Sat PC) in alveolar washes did not change after multiple doses of calf surfactant, indicating that subsequent doses did not alter the clearance of previous doses. The four doses of calf surfactant increased the alveolar Sat PC pool size by a factor of 2.5 only when measured 6 h after the last dose, but the total lung Sat PC pool size doubled, indicating a loss of most of the surfactant Sat PC to the lung tissue. In contrast, Surfactant-TA increased the alveolar pool size by a factor of 4 after the single dose and by a factor of 11 after the multiple doses, and the percentage clearance of labeled Sat PC from the lungs decreased with multiple doses, indicating an effect of subsequent doses on the initial dose. The quantity of Sat PC cleared from the lungs increased by about a factor of 2 after the multiple doses of Surfactant-TA. Although repetitive surfactant doses changed alveolar and lung Sat PC pool sizes the quantity of Sat PC cleared from the lungs increased, and the lungs accommodated the large amount of surfactant without short-term adverse effects. PMID- 2328712 TI - Morphometric estimation of regional differences in the rat lung. AB - To provide a safe basis for the sampling of tissue in future morphometric investigations of the rat lung, we searched for quantitative regional differences in pulmonary structure at light microscopic (LM) and electron microscopic (EM) levels. The lungs of 11 male rats about 6 weeks of age were fixed by standard intratracheal instillation of glutaraldehyde in the supine position and embedded either in paraffin for LM or in epoxy resin for EM investigation. Sampling of tissue was designed to test for differences between lobes and between central and peripheral lung parenchyma. LM morphometry was performed by manual point counting and by using a version of an improved automated image analyzer, Quantimet 720. EM morphometric results were obtained by manual point and intersection counting only. LM point counting showed that the proportion of parenchyma was highly constant in all lobes, varying only between 79.9% and 81.5%. In the left lung, which was partitioned into two equal halves, the amount of parenchyma was significantly lower in the apical region (mean values, 72.6% compared to 83.1%; p less than 0.002), which regularly contained the hilum. Quantimet analysis of central and subpleural lung portions revealed intralobar differences. The volume density of interalveolar septa and the air space surface density were significantly decreased in subpleural compared to central lung regions (by 7% and 4.6%, respectively). EM morphometry demonstrated that the interalveolar septa were evenly structured in all lobes except for the harmonic mean thickness of the air-blood barrier, which was lower in upper lobes. In addition, the volume density of interstitial cells was found to be significantly increased in central compared to peripheral parenchyma. The results indicate that for quantitative LM analysis the smallest possible sampling unit is an entire lobe. For EM morphometry, the often practiced approach to consider information drawn from one lobe representative for the whole lung seems to be appropriate for most parameters. In view of the structural differences between central and peripheral lung parenchyma, however, attention has to be paid to applying a properly weighted sampling procedure. Depending on the size of the lobe, the peripheral mantle (2 mm thick) can represent up to 75% of the lobar volume. PMID- 2328713 TI - Species comparisons of proximal alveolar deposition patterns of inhaled particulates. AB - Previous studies have shown that inhaled particles and fibers that are small enough to pass through the conducting airways deposit preferentially at alveolar duct bifurcations in the distal lungs of exposed rats. Because it is well documented that anatomic and physiologic differences exist among common experimental animals that may influence deposition patterns, we compared inhaled particle deposition patterns in alveolar regions of four rodent species. Proximal alveolar regions of hamsters and guinea pigs contain rudimentary respiratory bronchioles, whereas in rats and mice, terminal bronchioles lead directly into alveolar ducts. Groups of animals from one strain each of rats, mice, hamsters, and guinea pigs were exposed to aerosols of carbonyl iron (CI) particles for 1 h at design concentrations of 100 mg/m3. Immediately after exposure, the lungs of sham- and CI-exposed animals were perfusion fixed through the vasculature. Subsequently, lung tissues from exposed animals was analyzed for iron concentration; data indicated that total lung deposition of iron particles was highest in mice and hamsters. In addition, scanning electron microscopy of dissected lung tissue revealed that particle deposition patterns in the proximal regions of the distal lung were similar for all species, although greater numbers of CI particles per bifurcation were deposited in rats and mice compared to hamsters (p less than 0.05) and greater numbers were deposited in hamsters compared to guinea pigs (p less than 0.05). The data suggest that the presence of undeveloped respiratory bronchioles in the lungs of hamsters and guinea pigs has little influence on distal lung particle deposition patterns. It remains to be determined whether inhaled particles are deposited at similar sites in the lungs of species with well-developed respiratory bronchioles such as cats, nonhuman primates, and humans. PMID- 2328714 TI - Differential prostaglandin formation induced by convulsions in the brain of mice susceptible (DBA/2J) and resistant (CFLP) to acoustic stimulation. AB - Endogenous cerebral prostanoids possess anticonvulsant properties. This study investigates possible age-dependent anomalies of prostanoid synthesis in the brain of seizure-prone DBA/2J (DBA2) mice as compared to sound stimulus-resistant CFLP mice. Irrespective of the age of the animals, a large increase of prostaglandin (PG) D2 and E2 in the brain of CFLP mice was observed in response to pentylenetetrazol (PTZ)-, or electroshock (ES)-induced seizures. Significantly less PGD2 and PGE2 was formed in the brain of DBA2 mice at day 21 after birth when subjected to PTZ or ES convulsions. At 42 days of age, however, this deficit of cerebral PGD2 synthesis in DBA2 mice disappeared concomitantly with the age related decrease in audiogenic seizure (AS) susceptibility, whereas the deficit of PGE2 formation persisted. These results suggest that a deficiency of cerebral PGD2 synthesis may be one of the factors responsible for the AS susceptibility of the DBA2 mice. In contrast to PTZ or ES convulsions, acoustically induced seizures of the DBA2 mice were not accompanied by cerebral prostanoid synthesis. This supports the view that the pathways involved in AS are different from those involved in PTZ or ES models of epilepsy. PMID- 2328715 TI - Suppression of motor seizures after specific thalamotomy in chronic epileptic monkeys. AB - In the monkey with a chronic motor epileptogenic focus, thalamic lesions restricted to the anterior part of the ventro-postero-lateral nucleus produced a long-lasting improvement, leading in most cases to almost complete seizure suppression. This improvement was attributed to the interruption of a long-loop recurrent excitatory mechanism, involving muscular afferents which are known to relay in the thalamic region where lesions were produced. The specific nature of this effect was suggested by the preliminary results of lesions performed in thalamic regions with non-specific cortical projections. Compared with the pre lesional situation in which focal activity resulted in permanent motor troubles, the post-lesional state did not show any additional motor deficit. It is concluded that such lesions could be a new approach to controlling intractable motor epilepsies in man. PMID- 2328716 TI - Multidisciplinary analysis of patients with extratemporal complex partial seizures. II. Predictive value of semiology. AB - Eight patients were diagnosed as having extratemporal seizures based on their ictal electroclinical manifestations. The correlation between the focus based on semiology and that based on intracranial electrographic recording and surgical excision was excellent in five, good in three. The electroclinical manifestations of seizures are important data to consider in the diagnosis and treatment of extratemporal seizure foci. PMID- 2328717 TI - Efficacy of ACC-9653 (a phenytoin prodrug) in experimental status epilepticus in the rat. AB - Status epilepticus was induced by injection of homocysteine thiolactone to rats with epileptogenic cortical cobalt lesions. Either standard phenytoin or ACC-9653 (a phenytoin prodrug) was injected after the second generalized tonic-clonic seizure. Rats treated with ACC-9653 had significantly poorer treatment outcomes than rats treated with standard phenytoin, although no differences were found in the concentration of phenytoin in plasma or brain 65 min after injection. PMID- 2328718 TI - The role of the delta-lysin gene (hld) in the regulation of virulence genes by the accessory gene regulator (agr) in Staphylococcus aureus. AB - The synthesis of at least 14 extracellular toxins and enzymes in Staphylococcus aureus is regulated by a set of trans-acting elements from the agr (accessory gene regulator) locus. We have shown that the delta-lysin gene (hld) that is transcribed from a promoter immediately upstream of the agr locus, and which is positively controlled by agr, is part of this regulatory system. Deletion replacement mutagenesis of the chromosomal hld gene had the same pleiotropic effect on the synthesis of several virulence factors as agrA mutations. Characteristically, these mutants had an almost complete block in the synthesis of alpha-toxin, serin- and metalloprotease, whereas synthesis of protein A was greater than 10-fold higher than in the parental strain. Corresponding changes in the levels of alpha-toxin and protein A mRNAs were demonstrated by northern blotting experiments. The effects of the hld deletion mutation could be fully complemented by the hld gene on a plasmid. A plasmid insertion mutation in the 3' non-coding region of hld had a similar effect on exoprotein synthesis, indicating a role of the hld transcript in the regulation of exoprotein synthesis. This was confirmed by the finding that the effects of alpha-toxin and protein A synthesis by the hld deletion replacement mutation could be fully complemented by a hld allele in which we had introduced an early stop codon in the delta-lysin structural gene. However, the mutant hld allele could not complement the defect in production of extracellular proteases, indicating that delta-lysin may act in conjunction with its mRNA to regulate the expression of some exoprotein genes. PMID- 2328719 TI - The pat1 protein kinase controls transcription of the mating-type genes in fission yeast. AB - The developmental programme of fission yeast brings about a transition from mitotic cell division to the dormant state of ascospores. In response to nitrogen starvation, two cells of opposite mating type conjugate to form a diploid zygote, which then undergoes meiosis and sporulation. This differentiation process is characterized by a transcriptional induction of the mating-type genes. Conjugation can also be induced in pat1-ts mutants by a shift to a semi permissive temperature. The pat1 gene encodes a protein kinase, which also functions further downstream in the developmental pathway controlling entry into meiosis. We have analysed transcriptional induction of mating-type genes in various strains--with and without a pat1-ts allele. In wild-type cells of P mating type derepression occurs in two rounds. First, the mat1-Pc gene is induced in response to nitrogen starvation. Mutants in the map1 gene are defective in this process. In the following step the mat1-Pm gene is expressed in response to a pheromone signal generated by cells of M mating type. Both these controls are derepressed in the pat1-ts mutant at semipermissive temperature. Previous work has established that expression of the mating-type genes in the zygote leads to complete loss of pat1 protein kinase activity causing entry into meiosis. Thus, pat1 can promote its own inactivation. We suggest a model according to which a stepwise inactivation of pat1 leads to sequential derepression of the processes of conjugation and meiosis. PMID- 2328720 TI - The developmental fate of fission yeast cells is determined by the pattern of inheritance of parental and grandparental DNA strands. AB - A key feature for development consists of producing sister cells that differ in their potential for cellular differentiation. Following two cell divisions, a haploid Schizosaccharomyces pombe cell produces one cell in four 'granddaughters' with a changed mating cell type, implying nonequivalence of sister cells in each of two consecutive cell divisions. The observed pattern of switching is analogous to the mammalian 'stem cell' lineage by which a cell produces one daughter like itself while the other daughter is advanced in its developmental program. It is tested here whether sisters differ because of unequal distribution of cytoplasmic and/or nuclear components to them or due to inheriting a specific parental DNA chain at the mating type locus. Only the DNA strand-segregation model predicts that those cells engineered to contain an inverted tandem duplication of the mating type locus should produce equivalent sisters. Consequently, two 'cousins' in four related granddaughter cells should switch. The results verified the prediction, thus establishing that all cells otherwise fully possess the potential to switch. Therefore, the program of cell type change in S.pombe cell lineages is determined by the pattern of DNA strand inheritance at the mating type locus. A specific DNA sequence present at the mating type locus is postulated to be the cause of developmental asymmetry between sister cells. A general model for cellular differentiation is proposed in which the act of DNA replication itself is hypothesized to produce developmentally nonequivalent sister genomes. PMID- 2328721 TI - Identification of ras-related, YPT family genes in Schizosaccharomyces pombe. AB - Screening for genes homologous to ras in Schizosaccharomyces pombe resulted in the isolation of a homolog of Saccharomyces cerevisiae YPT1. This S. pombe gene, named ypt3, has a coding capacity of 214 amino acids interrupted by two introns, and is essential for cell growth. Two more YPT1 homologs were isolated from S. pombe using a part of the ypt3 gene as the probe. One of them, named ypt1, is highly homologous to S. cerevisiae YPT1 and mouse ypt1 and is essential for cell growth. This gene has four introns and encodes 203 amino acids. Its cDNA placed downstream of the S. cerevisiae GAL7 promoter could complement S. cerevisiae ypt1 , indicating that Sp ypt1 and Sc YPT1 are functionally homologous. The other isolate, named ryh1, and a fourth homolog, ypt2, have been characterized by Gallwitz and co-workers. The ypt1, ypt2 and ypt3 genes, but not ryh1, constitute a family, their products having double cysteine as their C terminus and serine in place of a glycine residue highly conserved in ras proteins (mammalian Gly-12 or S. pombe Gly-17). The physiological roles of these genes appear to be distinct because each of them is indispensable for cell growth. PMID- 2328722 TI - Structure-function studies of nerve growth factor: functional importance of highly conserved amino acid residues. AB - Selected amino acid residues in chicken nerve growth factor (NGF) were replaced by site-directed mutagenesis. Mutated NGF sequences were transiently expressed in COS cells and the yield of NGF protein in conditioned medium was quantified by Western blotting. Binding of each mutant to NGF receptors on PC12 cells was evaluated in a competition assay. The biological activity was determined by measuring stimulation of neurite outgrowth from chick sympathetic ganglia. The residues homologous to the proposed receptor binding site of insulin (Ser18, Met19, Val21, Asp23) were substituted by Ala. Replacement of Ser18, Met19 and Asp23 did not affect NGF activity. Modification of Val21 notably reduced both receptor binding and biological activity, suggesting that this residue is important to retain a fully active NGF. The highly conserved Tyr51 and Arg99 were converted into Phe and Lys respectively, without changing the biological properties of the molecule. However, binding and biological activity were greatly impaired after the simultaneous replacement of both Arg99 and Arg102 by Gly. The three conserved Trp residues at positions 20, 75 and 98 were substituted by Phe. The Trp mutated proteins retained 15-60% of receptor binding and 40-80% of biological activity, indicating that the Trp residues are not essential for NGF activity. However, replacement of Trp20 significantly reduced the amount of NGF in the medium, suggesting that this residue may be important for protein stability. PMID- 2328723 TI - A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence. AB - Interleukin 1 (IL-1) is a major soluble mediator of inflammation. Two human IL-1 genes, alpha and beta, have been isolated, which encode polypeptides with only 20 30% amino acid sequence homology. Unlike most secreted proteins, the two cytokines do not have a signal sequence, an unexpected finding in view of their biological role. Here we show that IL-1 beta is actively secreted by activated human monocytes via a pathway of secretion different from the classical endoplasmic reticulum--Golgi route. Drugs which block the intracellular transport of IL-6, of tumour necrosis factor alpha and of other secretory proteins do not inhibit secretion of IL-1 beta. Secretion of IL-1 beta is blocked by methylamine, low temperature or serum free medium, and is increased by raising the culture temperature to 42 degrees C or by the presence of calcium ionophores, brefeldin A, monensin, dinitrophenol or carbonyl cyanide chlorophenylhydrazone. IL-1 beta is contained in part within intracellular vesicles which protect it from protease digestion. In U937 cells large amounts of IL-1 beta are made but none is secreted. In these cells IL-1 beta is not found in the vesicular fraction, and all the protein is accessible to protease digestion. This suggests that intracellular vesicles that contain IL-1 beta are part of the protein secretory pathway. We conclude that IL-1 beta is released by activated monocytes via a novel mechanism of secretion which may involve translocation of intracellular membranes and is increased by stress conditions. PMID- 2328724 TI - Translocation of bFGF to the nucleus is G1 phase cell cycle specific in bovine aortic endothelial cells. AB - Primary cultures of adult bovine aortic endothelial (ABAE) cells require bFGF to grow. G1-arrested cells, obtained after 48 h without serum and bFGF, were found to enter S phase and grow synchronously for at least two generations on addition of bFGF. In growing cells bFGF was detected both in the cytoplasm (90%) and in the nucleus (10%) where it accumulates in the nucleolus. It was not detected in the nucleus of confluent cells. bFGF uptake was continuous in the cytoplasm throughout the cell cycle with a maximum in G2, while nuclear uptake occurred only in late G1. Cytoplasmic bFGF (18.4 kd) is cleaved into a 16.5 kd peptide in G1 (t1/2 = 30 min). In the nucleus the 18.4 kd form was the only one detected 2 h following bFGF addition and was then cleaved into the 16.5 kd in early S phase. These results are consistent with the possibility that in addition to the classical pathway of signal transduction, bFGF is directly translocated to the nucleus in late G1, and could play a role in replication and/or in transcription of rDNA. PMID- 2328725 TI - The presence of a DNA binding complex correlates with E beta class II MHC gene expression. AB - The class II major histocompatibility complex (MHC, Ia) antigens are a family of membrane proteins whose expression is strictly regulated. They have a limited tissue distribution and their expression is regulated both developmentally and in response to external stimuli. Here we report the identification of a DNA binding protein complex (termed complex A) within the murine E beta MHC gene, which is restricted to cells that express Ia antigens. Complex A binding activity is developmentally regulated in cells of the B lineage in accordance with class II expression and is responsive to two different Ia-inducing lymphokines, interferon gamma in macrophages and interleukin-4 in pre-B cells. The DNA target sequence in complex A includes three previously defined transcriptional motifs W, X and Y, and acts as a cis-acting transcription element. Complex A is present both in cells that are constitutive for class II MHC expression and in cells that have been induced for class II MHC expression. These results suggest that complex A may play a critical role in the regulation of class II MHC gene expression. PMID- 2328726 TI - Cloning, primary structure and properties of a novel human integrin beta subunit. AB - The originally described integrin beta subunits that define the three subfamilies of integrin heterodimers are beta 1, beta 2 and beta 3. In this paper, we describe the isolation of a cDNA coding for a novel human integrin beta subunit, designated as beta 5. The beta 5 cDNA was isolated from a human thymic epithelial cell library, using oligonucleotide probes that were designed from a region highly conserved among the known beta 1, beta 2 and beta 3 sequences. The beta 5 cDNA codes for 799 (or 796) amino acids, including a 23 amino acid leader sequence. There are 776 (or 773) amino acids in the mature protein, which includes a long extracellular domain of 696 amino acids, a transmembrane domain and an intracellular C-terminal domain of 57 amino acids. The beta 5 sequence resembled the known beta 3, beta 1 and beta 2 sequences by 55, 43 and 38%, respectively, including conservation of 56/56 cysteines. Rabbit antiserum was prepared against a 20 amino acid synthetic peptide predicted from the beta 5 C terminal sequence. This serum immunoprecipitated a beta 5 protein that was 100,000 Mr (reduced) and 95,000 Mr (nonreduced). Only a single alpha subunit was detected in association with beta 5, and that alpha subunit was immunochemically indistinguishable from the alpha v subunit previously found as part of the vitronectin receptor complex. By immunoprecipitation, beta 5 was most prevalent on carcinoma cell lines, was also present on hepatoma and fibroblast cell lines, and was absent from lymphoblastoid cells and platelets. PMID- 2328727 TI - Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. AB - The human progesterone receptor (hPR) cDNA, synthesized from T47D breast cancer cells, and the hPR gene 5'-flanking region were cloned and sequenced. Comparison of the cDNA-deduced amino acid sequence with other PR homologues demonstrated the modular structure characteristic of nuclear receptors. As in the case of the chicken homologue, there are two hPR forms, A and B, which originate from translational initiation at AUG2 (codon 165) and AUG1, respectively. Northern blot analysis of T47D mRNA using various cDNA derived probes identified two classes of hPR mRNAs, one of which could code for hPR form B, while the other one lacked the 5' region upstream of AUG1. S1 nuclease mapping and primer extension analyses confirmed that the second class of hPR transcripts are initiated between +737 and +842 and thus encode hPR form A, but not form B. By using the hPR gene 5'-flanking sequences as promoter region in chimeric genes, we show that a functional promoter (located between -711 and +31) directs initiation of hPR mRNAs from the authentic start sites located at +1 and +15. Most importantly, initiation of transcription from chimeric genes demonstrated the existence of a second promoter located between +464 and +1105. Transient co-transfection experiments with vectors expressing the human estrogen receptor showed that both promoters were estrogen inducible, although no classical estrogen responsive element was detected in the corresponding sequences. When transiently expressed, the two hPR forms similarly activated transcription from reporter genes containing a single palindromic progestin responsive element (PRE), while form B was more efficient at activating the PRE of the mouse mammary tumor virus long terminal repeat. Transcription from the ovalbumin promoter, however, was induced by hPR form A, but not by form B. PMID- 2328728 TI - Transcription factor Oct-2A contains functionally redundant activating domains and works selectively from a promoter but not from a remote enhancer position in non-lymphoid (HeLa) cells. AB - In non-lymphoid cells such as HeLa cells, ectopic expression of the lymphocyte specific transcription factor Oct-2A can activate reporter genes whose promoters consist of a single octamer sequence (ATTTGCAT) upstream of a TATA box. While the factor is strongly active in a promoter position, it tails as an enhancer factor: an enhancer consisting of multiple copies of the octamer sequence placed downstream of the reporter gene is not active in HeLa cells, even at high concentration of Oct-2A. In B lymphoid cells, however, the same enhancer is highly active. This could mean that an additional factor is required for enhancer activation in B cells. Furthermore, we have tested the transcriptional activation potential of Oct-2A with a series of N-terminal and C-terminal deletions. We show that a glutamine-rich domain near the N-terminus is required for full activity. Otherwise, large segments of the N-terminal half or the entire C-terminal region are dispensable in our assay, as long as the deletions do not impinge on the conserved POU domain which is sufficient for DNA binding. While N-terminal and C terminal regions can functionally compensate for each other, a combined deletion that only retains the POU domain is a strong down mutation. We also find that activity depends on the promoter structure of the reporter gene: the POU domain by itself shows some activity with a promoter where the octamer sequence is located very close to the TATA box, but no activity with another promoter construction where the octamer sequence is located further upstream. The two promoters also respond differently to the deletion of the glutamine-rich stretch important for transcriptional activation. From these experiments we consider it likely that the natural octamer factor variants can selectively activate the different naturally occurring octamer-containing promoters. PMID- 2328730 TI - Replacement of histone H1 by H5 in vivo does not change the nucleosome repeat length of chromatin but increases its stability. AB - In vivo competition between histones H1 and H5 for chromatin has been studied in rat sarcoma XC10 cells transfected with a glucocorticoid responsive MMTV-H5 gene. Activation of H5 expression results in accumulation of H5 in the nuclei where it partially replaces H1. H5 displaces H1 from its primary binding sites presumably during chromatin replication and also binds with high affinity to secondary chromatin sites normally not occupied by H1. Replacement of H1 by H5 to levels similar to those of mature chicken erythrocytes does not alter the nucleosome repeat length of chromatin. This indicates that H5 is not solely responsible for the increase in nucleosome spacing of maturing erythroid cells. Exchange of H1 by H5 in vivo or in vitro results in a higher compaction/stability of chromatin. PMID- 2328729 TI - The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription. AB - Many studies indicate that the cell type-specific transcription factor OTF-2 plays a central role in the lymphoid-specific transcription of immunoglobulin genes. In order to better understand the mechanisms regulating transcriptional selectivity, we have initiated a functional dissection of OTF-2. By mutagenesis of an OTF-2 cDNA and by subsequent transfection into non-lymphoid cells we have defined two domains that are required jointly for high levels of transcription from a lymphoid-specific target promoter. One of these domains, located at the extreme carboxy-terminus, is rich in proline. The other domain, which appears to represent a novel type, is located upstream of the POU-specific box and contains clusters of intermingled proline, glutamine and leucine residues. Point mutations that change either groups of glutamine or groups of leucine show that both types of amino acids are required for function. Our data indicate that a high content in a particular amino acid does not necessarily suffice to generate a potent activation domain but that severe structural constraints may also play a major role. PMID- 2328731 TI - The three-way DNA junction is a Y-shaped molecule in which there is no helix helix stacking. AB - We have studied the structure of a number of three-way DNA junctions that were closely related in sequence to four-way junctions studied previously. We observe that the electrophoretic mobility of the species derived by selective shortening of one arm of a junction are very similar whichever arm is shortened, and that this remains so whether or not magnesium is present in the buffer. This suggests that the angles subtended between the arms of the three-way junctions are similar. All thymine bases located immediately at the junction are reactive to osmium tetroxide, indicating that out-of-plane attack is not prevented by helix helix stacking, and this is also independent of the presence or absence of metal cations. The results suggest that the three-way junction cannot undergo an ion induced conformational folding involving helical stacking, but remains fixed in a Y-shaped extended conformation. Thus the three- and four-way junctions are quite different in character in the presence of cations. PMID- 2328732 TI - Suramin-treated HT29-D4 cells grown in the presence of glucose in permeable culture chambers form electrically active epithelial monolayers. A comparative study with HT29-D4 cells grown in the absence of glucose. AB - The clonal cell line HT29-D4 is able to differentiate by two different ways: i) by replacing glucose by galactose in the culture medium; ii) by addition of suramin (a drug known to interfere with the growth promoting activity of growth factors) in the medium. In both cases the transition in the organization of the cell monolayer occurred without cell loss. The two ways (i.e., glucose starvation or suramin addition) lead to polarized cells which generate electrically active cell monolayers (Fantini et al., Biol. Cell 65, 163-169 (1989) and this paper). Yet several important differences can be observed at the morphological or at the electrophysiological levels. 1) The suramin-treated cells (HT29-D4-S cells) organized into monolayers of high (40-50 microns) columnar cells while glucose starved cells (HT29-D4-Gal cells) were rather cuboidal (20-25 microns). 2) HT29 D4-S cells were highly polarized; the nucleus was rejected at the basal side of the cell and lysosomes in the upper part of the cytoplasm. Numerous lipid-like droplets surrounded with glycogen were observed underneath the nucleus. HT29-D4 Gal cells never presented such a degree of organization. 3) The transepithelial resistance and the potential difference of HT29-D4-S monolayers reached values significantly higher than those for HT29-D4-Gal monolayers, reflecting a higher degree of organization. Specific proteins such as sucrase-isomaltase, alkaline phosphatase and carcinoembryonic antigen were localized exclusively on the apical membrane while human lymphocyte antigen (HLA) class I molecules were restricted to the basolateral membrane for both HT29-D4-S and HT29-D4-Gal cells. The present data demonstrate that the same cells can generate a different degree of cellular organization according to the experimental conditions of cell growth, the most elaborate state of differentiation being obtained in the presence of suramin. PMID- 2328733 TI - Distribution of intracellular free calcium in quiescent BALB/c 3T3 cells stimulated by platelet-derived growth factor. AB - A digital imaging microscope and fluorescent Ca(2+)-sensitive probe (Fura 2) were used to study the spatial location and time course of increases in free intracellular calcium (Cai) induced by platelet-derived growth factor (PDGF). Microinjection of Fura 2 acid avoided problems of incomplete deesterification of Fura 2-acetoxymethyl ester (Fura 2/AM) and dye localization in cellular organelles. PDGF stimulated a rapid increase in Cai (up to 8-fold increase) in both the nucleus and the cytoplasm in approximately half of the quiescent BALB/c 3T3 cells. Cai changes were both spatially and temporally heterogeneous, the latter including both transient (1-2 min) and prolonged increases (greater than 5 min) in the same cell. PDGF stimulated mitogenesis and Cai increases in approximately the same percentage of cells. Moreover, large intracellular concentrations of a Ca2+ buffer (Quin 2) inhibited both Cai increases and mitogenesis stimulated by PDGF. Thus, Ca2+ increases in the nuclear and/or cytosolic compartments appear to be required for the stimulation of mitogenesis by polypeptide growth factors such as PDGF. PMID- 2328734 TI - Uncoupling of ganglioside biosynthesis by Brefeldin A. AB - We have studied the effect of Brefeldin A (BFA), an antiviral antibiotic, on glycosphingolipid metabolism in primary cultured cerebellar cells. Cells were labeled metabolically with [14C]galactose, or pulse-labeled with precursors of glycosphingolipid biosynthesis; i.e., [14]serine, [3H]palmitic acid or [3H]sphingosine. In all cases BFA (1 microgram/ml) strongly inhibited (75-95%) ganglioside biosynthesis beyond the stage of GM3 and GD3, that is the formation of GM1, GD1a, GT1b and GQ1b. Simultaneously an accumulation of GlcCer, LacCer, GM3 and GD3 was observed (up to 2000%). These effects could be reversed fully by removal of the BFA from the culture medium. These results indicate that the LacCer-, GM3- and GD3-synthases of murine cerebellar cells are localized together on the proximal site of the Golgi apparatus, probably in the cis-Golgi compartment. It is probable that sphingomyelin synthase and some of the other glycosyltransferases involved in ganglioside biosynthesis are localized in distinct compartments beyond the cis Golgi. PMID- 2328735 TI - Immunoelectron microscopic studies on the location of ribosomal proteins on the surface of the 40S ribosomal subunit from rat liver. AB - Seven ribosomal proteins have been localized by means of immunoelectron microscopy on the surface of the 40S ribosomal subunit from rat liver using monospecific antibodies. The location of ribosomal proteins S13/16, S19, and S24 is described for the first time, and that of ribosomal proteins S2, S3, S3a, and S7, which has been published previously on the basis of experiments performed with less well characterized antibody preparations [Lutsch et al., Mol. Gen. Genet. 176, 281-291 (1979) and Biomed. Biochim. Acta 42, 705-723 (1983)], is corrected in this paper. The results are discussed with respect to the involvement of these proteins in functional sites of the 40S ribosomal subunit. PMID- 2328736 TI - Immunocytochemical localization of rabbit gastric lipase and pepsinogen. AB - Lipase and pepsin activities were determined in rabbit gastric biopsy specimens. Lipase activity was found to be restricted to a small part of the fundic mucosa, near the cardia, whereas pepsin activity spread over about two thirds of the total fundic area, overlapping that of lipase. The cells producing these two enzymes were labeled by immunofluorescence using polyclonal antibodies against rabbit gastric lipase (RGL) or antibodies against rabbit pepsinogen. The immunocytochemical localization showed unequivocally that RGL and pepsinogen, which were both present in the cardial area, were in fact located in different gastric cells. The cells producing pepsinogen were in the lower base of the gastric fundic glands, whereas the cells producing RGL were in the upper base of the same glands. The cells producing pepsinogen and RGL showed no significant morphological differences. In the part of the fundic area, where only pepsin activity was detected, cells producing pepsinogen covered both the lower and the upper base of the gastric glands. No chief cells were observed in the antral mucosa. RGL and pepsinogen could represent useful gastric enzyme markers for cellular differentiation studies. PMID- 2328737 TI - Involvement of mitochondria in cell degeneration. AB - Human WI-38 fibroblasts were microinjected with isolated mitochondria, and survival of the injected cells was followed. More than 95% of the cells were alive and able to divide when they were injected with fresh mitochondrial preparations having a high respiratory control ratio (RCR). The presence of lysosomes was found to be toxic to the cells, and hence mitochondria had to be isolated without being contaminated by lysosomes. The microinjection of isolated mitochondria from old rats induced a 20% degeneration of the injected cells. The proportion of dead cells was also found to be dependent on the metabolic control of the injected mitochondria. Moreover, an easily metabolized energy substrate such as D(-)-beta-hydroxybutyrate sodium salt was able to inhibit, in a dose dependent manner, cell degeneration induced by microinjection of uncoupled mitochondria. These results suggest that modifications of mitochondria leading to their uncoupling are harmful to the cells, and this can explain some of the degenerative processes observed in natural or externally induced cell death. PMID- 2328738 TI - Nucleation of macrotubules on double-walled microtubule seeds. AB - It is known that histone H1 is able to cause the formation of double-walled microtubules from microtubule protein. Now, we demonstrate that in dependence on the mass ratio H1/microtubule protein upon addition of tubulin to short pieces of double-walled microtubules either their inner or their outer wall elongates resulting in normal microtubules or in macrotubules, respectively. Because of their genesis we suggest that macrotubules like double-walled microtubules (see Unger et al., Eur. J. Cell Biol. 46, 98-104 (1988)) expose those sides of tubulin dimers at their surface which usually form the lumen face of microtubules. PMID- 2328739 TI - Localization of cAMP-dependent protein kinase subunits along the secretory pathway in pancreatic and parotid acinar cells and accumulation of the catalytic subunit in parotid secretory granules following beta-adrenergic stimulation. AB - Catalytic (C) and regulatory (RI and RII) subunits of cAMP-dependent protein kinases were localized by immunoelectron microscopy in cisternae of the rough endoplasmic reticulum (rER) and in the Golgi complex of rat pancreas or parotid cells. Zymogen granules of the exocrine pancreas showed C- and RI immunoreactivity, secretory granules of parotid acinar cells only RII immunoreactivity. Injection of rats with isoproterenol (IPR) increased in the parotid gland the number of acinar cells with RII-labeled granules. In addition, it led to the appearance of C-immunoreactivity in the condensing vacuoles and secretory granules with a maximum at 24 h after stimulation. This was confirmed by enzyme-linked immunosorbent assay (ELISA) determinations of C- and RII subunits in secretory granules isolated from stimulated and control parotid glands. The amount of immunoreactive C-subunits in the secretory granules increased further following repeated injections of the beta-agonist. These findings suggest the existence of secretory forms of cAMP-dependent protein kinase R- and C-subunits and their separate regulation. PMID- 2328740 TI - Differential binding of the lectins Griffonia simplicifolia I and Lycopersicon esculentum to microvascular endothelium: organ-specific localization and partial glycoprotein characterization. AB - The lectins Griffonia simplicifolia I and Lycopersicon esculentum were used to assess the presence of endothelium-specific glycoproteins in the microvasculature of the rat myocardium, diaphragm and superficial cerebral cortex. Organs fixed by intravascular perfusion were processed to obtain semithin (0.5 micron) and thin (less than 0.1 micron) frozen sections that were reacted with biotinylated lectin followed by streptavidin conjugated to Texas Red, for semithin sections, or by streptavidin conjugated to 5-nm colloidal gold particles, for thin sections. Lycopersicon esculentum lectin exclusively labeled the endothelium of all small vessels in all three microvascular beds; it did not bind to components of either the parenchyma or the extracellular matrix. Griffonia simplicifolia I lectin exclusively labeled the endothelium of the entire microvasculature in the myocardium and diaphragm, but marked primarily pericytes in the cerebral microvasculature. It did not label any parenchymal or interstitial organ component. At the electron microscope level, the lectin Griffonia simplicifolia I labeling was associated with the plasmalemma proper and especially with plasmalemmal vesicles and their introits, and Lycopersicon esculentum lectin bound primarily to the luminal plasmalemma in the microvascular beds of the myocardium and diaphragm. In the cerebral cortex, labeling of the microvasculature was clearly different: Griffonia simplicifolia I bound primarily to pericytes and vascular smooth muscle cells whereas Lycopersicon esculentum labeled only the microvascular endothelium. Lysates prepared from the myocardium, diaphragm and cerebral cortex were processed through Griffonia simplicifolia I lectin affinity separation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the fraction obtained. A number of putative endothelium-specific glycoproteins was detected and found to differ qualitatively and quantitatively from organ to organ. The most prominent polypeptide, approximately 97 kDa, was present in substantial amounts in the myocardium and diaphragm, but in considerably lower concentration in the cerebral cortex. The reverse applied for a approximately 55 kDa protein. The preferential distribution of the approximately 97 kDa protein parallels differences in Griffonia simplicifolia I lectin binding by fluorescence and electron microscopy on sections of the corresponding organs. The results provide further evidence for the existence of endothelial glycoproteins specific for different microvascular beds and possibly connected with local functional differentiations. PMID- 2328741 TI - Endocytosis, intracellular transport and transcytosis of the toxic protein ricin by a polarized epithelium. AB - The toxic plant protein ricin binds to both the apical and basolateral surface domains of MDCK (strain I) cells grown on polycarbonate filters. Endocytosis of 125I-labeled ricin was not only higher from the basolateral than from the apical surface--an observation which can be explained by the higher surface area of the basolateral surface--but it also appeared to be more efficient when measured as a percentage of total cell-associated ricin. Monovalent ricin-horseradish peroxidase (Ri-HRP), which is known to behave like native ricin with respect to intracellular transport, also binds to, and is taken up from, both the apical and the basolateral surfaces. Initially, after 10 to 15 min, molecules taken up from the two surface domains at 37 degrees C are present in two separate (basolateral and apical) early endosomal populations. This can also be obtained by incubating for 60 min at 18 degrees C. However, after 30 to 60 min at 37 degrees C, most internalized ligand is found in apical lysosomes, regardless from which surface endocytosis took place. Experiments with endocytosis of cationized ferritin from the apical pole and HRP or Ri-HRP from the basolateral pole showed that intermixing in apical lysosomes (or prelysosomes) of molecules taken up from the two poles occurs. Bidirectional transcytosis involving coated pits of both 125I labeled ricin and Ri-HRP was demonstrated and was found to be most efficient (as measured in per cent of endocytosed toxin) from the apical pole. Transcytosis was strongly reduced at 18 degrees C, and no transepithelial transport of ricin could be measured at 4 degrees C. Transcytosed ricin was intact and could intoxicate new cells. Finally, delivery of ricin internalized from both the apical and the basolateral surface to the apically localized trans-Golgi network occurred at 37 degrees C but not at 18 degrees C, and ricin inhibited protein synthesis largely with the same kinetics following uptake from the two poles. Incubation at 18 degrees C strongly inhibited the toxic effect of ricin. These data show that ricin can intoxicate epithelia from both sides and also penetrate tight epithelial barriers in intact form. PMID- 2328742 TI - Science and the environment--challenges, risks, and the future. PMID- 2328743 TI - Dose adjustment of nifedipine in hypertensive patients. AB - Ten patients with essential hypertension (WHO grade I-II) were treated in an open dose-adjustment study with the standard regimen of slow-release nifedipine 20 mg b.d. for 2 weeks and with an individualized dose for 6 weeks. The optimum dose, defined as that producing a pre-dose diastolic blood pressure (dBP) of 90 mm Hg at steady state, was determined from the individual concentration-effect relationship after a test-dose of 20 mg. On standard therapy, the reduction in pre-dose dBP was inadequate in 4 patients and it was excessive in 1 patient. After 2 weeks of individualized treatment, the required pre-dose antihypertensive effect was obtained in all patients. The individual doses required were 10 mg b.d., 10 mg t.d.s. 20 mg b.d., 20 mg t.d.s. and 20 mg q.d.s. One patient dropped out of the study because of side effects. Loss of the antihypertensive effect was observed in one patient after 6 weeks of treatment. On the optimized dose, the average value of the pre- and 2 h post-dose steady state nifedipine concentrations (27.6 micrograms/l) compared well with model-derived optimum concentrations (28.6 microliters/l) (r = 0.9210). The results show that the dose of nifedipine can be accurately predicted using the individual concentration effect relationship after a single dose. PMID- 2328744 TI - Risk of acute upper gastrointestinal bleeding in patients with ulcerative disease and treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Results from the Comprehensive Hospital Drug Monitoring Berne (CHDM). AB - The hospital prevalence rate for upper gastrointestinal ulcerative disease in 28,531 inpatients consecutively admitted in two teaching hospitals in the Comprehensive Hospital Drug Monitoring (CHDM) in Berne, from 1974 to 1985, was 2.2% (1.8% for gastric or duodenal ulcer, and 0.4% for erosive gastritis). This was based on the evaluation of 634 patients after exclusion of the subgroup of patients with hepatic cirrhosis or upper gastrointestinal neoplasia. After exclusion of patients on anticoagulant therapy (n = 73), 561 (= 100%) patients could be further studied. Of them, 33.3% (n = 187) were found to have been exposed to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, within 21 days prior to confirmation of the diagnosis. The observed relative risk (RR) of developing a substantial acute upper gastrointestinal bleeding (Hb less than 10 g/100 ml for men, and less than 9 g/100 ml for women, or a decrease in Hb of more than 25%) was 1.61 when patients exposed to NSAIDs (n = 187) were compared to patients not exposed to those drugs (n = 374). Although there was no significant sex difference overall, the RR for gastrointestinal bleeding differed considerably in the various age-groups; it was elevated in men under 40 years (RR = 2.86) and in women over 60 years of age (RR = 1.89), as compared to the mean RR of 1.61. PMID- 2328745 TI - Potentiation of calcitonin by corticosteroids during the treatment of the hypercalcaemia of malignancy. AB - Some patients treated for the hypercalcaemia of malignancy develop renal tubular resistance to the effects of calcitonin which is independent of concurrent changes in sodium excretion. This type of resistance can be overcome by the addition of corticosteroids. In other patients apparent renal resistance to calcitonin is a consequence of reduced sodium excretion and is unaffected by corticosteroids. PMID- 2328746 TI - Effect of cimetidine and ranitidine on plasma theophylline in patients with chronic obstructive airways disease treated with theophylline and corticosteroids. AB - Thirty adults with chronic obstructive airways disease, who were stabilised on theophylline and corticosteroids, took part in a single blind study of the effects of cimetidine and ranitidine on plasma theophylline concentrations. The patients were randomised to receive either 150 mg ranitidine b.d. or 400 mg cimetidine b.d. for one week and serial plasma theophylline measurements were made over a 12-hour period on two consecutive days before, during and after treatment with the H2-antagonist. There was a significant increase in plasma theophylline during treatment with cimetidine; two patients had levels greater than 20 mg.l-1. The average increase in the theophylline concentration due to cimetidine was 32%. There was no significant change in plasma theophylline during ranitidine administration. No adverse effect occurred in any patient during the study. PMID- 2328747 TI - Difference in action between oral triazolam and zopiclone. AB - The effects of oral triazolam 0.25 mg and zopiclone 7.5 mg in 7 supine volunteers were compared by means of quantitative measurements of the EEG, saccadic eye movements, visual analogue scale (VAS) for alertness, critical flicker fusion frequency (CFF) and the Maddox wing. Zopiclone reached its maximum effect earlier (62 min) than triazolam (91 min; CFF). On linear regression analysis the average rate constant (regression coefficient) of onset of action of zopiclone was significantly greater than that of triazolam (0.29 vs. 0.17). Triazolam and zopiclone had similar effects, but zopiclone seemed to have a faster onset of action, probably indicating swifter absorption in supine subjects. Quantitative EEG evaluation gave parallel results to the other parameters used, but triazolam and zopiclone showed a dissimilar mechanism of action, as characterized by changes in the alpha frequency. PMID- 2328748 TI - N-acetylation phenotyping with sulphadimidine in a Turkish population. AB - The distribution of acetylator phenotypes was studied in 244 unrelated Turkish subjects. Sulphadimidine and its acetylated metabolite were measured in 6 h plasma and 0-6 h urine samples after an oral dose of 10 mg/kg. Subjects with 37.5% or less acetylsulphadimidine in plasma were regarded as slow acetylators and the others as rapid acetylators. The mean plasma concentration of acetylsulphadimidine was about 2.5-times lower in slow acetylators. Urinary excretion of total sulphadimidine (free + acetylated) was also significantly lower in slow acetylators compared to rapid acetylators. The frequency of slow acetylators was 60.7% in the population (95% confidence interval 54.3% to 66.8%). Sulphadimidine acetylation showed no variation due to sex, age, body weight or pre-existing disease. PMID- 2328749 TI - Peripheral haemodynamic effects of smoking in habitual smokers. A methodological study. AB - The effect of smoking on forearm haemodynamics was studied in four groups of healthy subjects, who had all smoked cigarettes (10-15 cigarettes/day) on average for 10 years. Changes in heart rate, blood pressure, forearm blood flow, forearm vascular resistance and pulse wave velocity were determined before and every 15 min for 75 min after smoking two cigarettes within 10 min. The inhaled nicotine was about 2.2 mg. There was no significant difference between the four groups in any haemodynamic variable before or after smoking, which indicated adequate reproducibility of the parameters studied and so made it possible to pool the results from all 30 subjects. Smoking significantly increased blood pressure, heart rate and pulse wave velocity and decreased forearm blood flow. Forearm vascular resistance remained unchanged. The rises in systolic blood pressure and pulse wave velocity were transient and both peaked (7% and 28%, respectively) 15 min after smoking. In contrast, heart rate and diastolic blood pressure remained significantly elevated and forearm blood flow was significantly decreased throughout the 75 min follow-up. The maximal changes were: heart rate +34%, diastolic blood pressure +17%, and forearm blood flow -24%. It is concluded that smoking produces statistically significant changes in forearm haemodynamics affecting both small and large arteries. The reproducibility of the study design means that it can be used to evaluate substances which may antagonize the haemodynamic effects of tobacco smoking. PMID- 2328750 TI - Pharmacokinetics of metamizol metabolites in healthy subjects after a single oral dose of metamizol sodium. AB - The linearity of the pharmacokinetics of the metamizol metabolites 4-methyl-amino antipyrine (4-MAA), 4-amino-antipyrine (4-AA), 4-formyl-aminoantipyrine (4-FAA), and 4-acetyl-amino-antipyrine (4-AcAA) has been studied after administration to 15 healthy male volunteers of single oral doses of 750, 1500, and 3000 mg metamizol. The trial was open, randomized, and cross-over, with a one-week interval between dosing days. Metabolite concentrations in serum and urine were measured using reverse-phase HPLC. The mean Cmax of 4-MAA increased linearly with dose whereas its AUC was not proportional to dose after administration of 1500 and 3000 mg. With 4-AA, the increase in mean Cmax was linear, but the increase in AUC was not. The increases in mean Cmax and AUC for 4-FAA after doses of 1500 and 3000 mg were not proportional to the dose. The increases in mean Cmax and AUC for 4-AcAA were roughly proportional to the increase in dose. There were no significant differences in renal clearance between doses for any of the four metabolites. The observed non-linearities reflect the saturability of metabolic pathways. However, although they were statistically significant, the deviations from linearity were marginal and should not be of clinical relevance to the analgesic efficacy of metamizol in the dose range tested. PMID- 2328751 TI - Pharmacokinetics of (+)-rolipram and (-)-rolipram in healthy volunteers. AB - Plasma levels of S-(+)-rolipram and R-(-)-rolipram in six healthy male volunteers were measured by radioimmunoassay after intravenous injection of 0.1 mg and oral administration of 1.0 mg of the pure enantiomers. Following i.v. treatment, plasma levels of both isomers declined in three phases, with half-lives of 0.2 h, 0.6-0.9 h and 6-8 h. Total clearance was 6 ml.min-1.kg-1. Oral administration of 1.0 mg gave a peak concentration of 16 ng.ml-1 after 0.5 h. Bioavailability of (+)-rolipram was 77% and of the (-) enantiomer it was 74%. There was no significant difference in Cmax, half-life, total clearance or bioavailability between the two enantiomers. PMID- 2328752 TI - A single dose desensitization for summer hay fever. Results of a double blind study-1988. AB - A new type of desensitising vaccine, enzyme potentiated was subjected to a double blind randomised study during the hay fever season. The vaccine is a convenient single injection given in March and the results show good protection throughout the grass pollen season. PMID- 2328753 TI - Pharmacokinetics of aspirin in aged Indians. AB - The pharmacokinetics of aspirin (ASA) has been studied in elderly Indians (greater than 60 y) of either sex, composing, apparently healthy subjects controlled hypertensives and NIDDM diabetics, in comparison with healthy young subjects. Serum salicylate levels were estimated a 0, 0.5, 1, 2, 4 & 8 h after ASA. The pharmacokinetics of serum salicylate were not changed in elderly subjects as compared to the young after the first dose or after one week of ASA therapy, although greater variability was observed in the elderly. Various laboratory investigations were unaltered after one week in all the groups, except that one elderly hypertensive patient gained weight, and a young subject showed an increase in SGOT & SGPT. PMID- 2328754 TI - Influence of midazolam on the plasma concentrations of mepivacaine after lumbar epidural injection in children. AB - Twenty children undergoing surgery received a lumbar block using 0.4 ml/kg mepivacaine 2.0%. They were randomized into two groups, one of which received midazolam 0.4 mg/kg rectally as premedication. Midazolam administration did not significantly influence the plasma concentrations of mepivacaine. PMID- 2328755 TI - Effects of azaprophen, scopolamine and trihexyphenidyl on schedule-controlled behavior, before and after chronic physostigmine. AB - The effects of the muscarinic acetylcholine receptor antagonists, azaprophen (0.3 10.0 mg/kg), scopolamine (0.01-3.0 mg/kg) and trihexyphenidyl (0.3-10.0 mg/kg) were examined in rats using a VI 18 s schedule of food reinforcement, before and after chronic physostigmine administration. All three compounds produced dose dependent decreases [corrected] in the rate of responding. Scopolamine was more potent than trihexyphenidyl which was equipotent to azaprophen. All three compounds antagonized the response rate-decreasing effects of physostigmine in a dose-dependent fashion. Following 43 consecutive daily administrations of physostigmine (0.4 mg/kg), partial tolerance developed to its response rate decreasing effects. When the three antagonists were again examined (alone and in combination with physostigmine), their effects were generally unchanged. These results further characterize the behavioral effects of azaprophen, scopolamine and trihexyphenidyl. These results also suggest that tolerance to physostigmine's effects can be mediated through behavioral rather than pharmacological mechanisms. PMID- 2328756 TI - Modulation of GABA-stimulated Cl- flux by a benzodiazepine agonist and an 'inverse agonist' after chronic flurazepam treatment. AB - Rats treated one week with flurazepam were killed while still on the drug or 48 h after termination of drug treatment. The brain 'microsac' preparation derived from the cerebral cortices was used for studying the GABA-stimulated chloride influx. There was no significant change in the basal or GABA-stimulated influx between control and treated groups. However, the effect of flunitrazepam to enhance 10 microM GABA-stimulated influx was significantly reduced, indicating tolerance. Methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3- carboxylate (DMCM), an 'inverse agonist' at benzodiazepine receptors, dose dependently inhibited 50 microM GABA-stimulated influx; chronic treatment did not alter the effect of DMCM. This study demonstrates that one week treatment with flurazepam produces tolerance to benzodiazepines without any change in the effect of GABA or DMCM. This indicates that GABA and benzodiazepine sites are differently modulated after chronic treatment with benzodiazepines. However, since both benzodiazepine and DMCM act on the same receptors it appears that the different 'domains' on the benzodiazepine receptor are differently altered during chronic treatment. PMID- 2328757 TI - Characterization of muscarinic acetylcholine receptors in human labial salivary glands. AB - Muscarinic acetylcholine receptors were studied in human labial salivary glands with (-)-[3H]MQNB. The radioligand bound with a Kd value of 150 pM. The density of muscarinic receptors was 220 fmol/mg protein. Most muscarinic antagonists bound to a homogeneous population of muscarinic receptors in this tissue. However, the inhibition curves of pirenzepine had a Hill slope of 0.57 and could be analyzed by a two site model. These results suggest that the muscarinic receptors in human labial salivary glands are a mixture of M1 and M3 types. PMID- 2328758 TI - Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions. AB - The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM 9384), a cyclic derivative of GABA, were investigated and compared with those of aniracetam in an animal model of amnesia, using a passive avoidance task with animals that have GABAergic neuronal dysfunctions. Pre- and post-training administration of DM-9384 and aniracetam ameliorated bicuculline-induced amnesia, as indicated by parameters such as % retention and step-down latency. DM-9384 ameliorated picrotoxin-induced amnesia when administered pre-training, but not when administered post-training. Aniracetam failed to improve the picrotoxin induced amnesia. DM-9384 displaced [3H]muscimol binding to GABAA receptors (-log IC50 = 8.07 M; Hill value = 0.23 +/- 0.04), but failed to displace about 20% of the specific muscimol binding, whereas aniracetam showed only a weak effect (-log IC50 = 3.63 M; Hill value = 0.37 +/- 0.06). From these results, it appears that DM-9384 ameliorated the GABA antagonist-induced amnesia by interacting with some GABAA receptors directly and/or indirectly. PMID- 2328759 TI - Pre- and postjunctional effects of N-ethylmaleimide in the isolated mouse vas deferens. AB - The influence of N-ethylmaleimide (NEM) on contractions due to exogenously applied noradrenaline and bethanechol and on the inhibitory effects of clonidine, of the enkephalin derivative, FK 33-824, and 2-chloroadenosine (2-CLA) on field stimulation-response curves and [3H]noradrenaline [( 3H]NA) release was studied in the isolated mouse vas deferens. Exposure to NEM (60 microM: 10 min) caused a 30% reduction of the maximal contraction due to NA but nearly abolished the response to bethanechol. NEM partially reversed the depression of the pulse width response curves by clonidine and FK 33-824 but was without effect with 2-CLA. The contractions evoked by stimulation frequencies above 20 Hz were depressed by NEM both in presence and absence of the agonists. NEM diminished the inhibition of the stimulation-evoked release of [3H]NA by the three agonists. The prejunctional effect of NEM was markedly influenced by the stimulation parameters. These findings support the suggestion that the inhibition mediated by alpha 2 adrenoceptors, mu- and P1-receptors in the mouse vas deferens is NEM-sensitive and possibly transmitted by a pertussis toxin-sensitive G-protein. PMID- 2328760 TI - Inhibitory effects of cadralazine and its metabolite, ISF-2405, on contractions and the level of cytosolic Ca2+ in vascular smooth muscle. AB - The inhibitory effects of a hypotensive agent, cadralazine and its metabolite, ISF-2405, on the level of cytosolic Ca2+ ([Ca2+]cyt) and on contractions were examined in isolated vascular smooth muscle. Cadralazine slightly inhibited the transient norepinephrine-induced contraction in rabbit aorta and canine femoral, renal and mesenteric arteries and saphenous vein, and prostaglandin F2 alpha induced contractions in canine basilar and coronary arteries. In contrast, ISF 2405 inhibited the contractions induced by prostaglandin F2 alpha in canine basilar and coronary arteries and those induced by norepinephrine in canine renal and femoral arteries and rabbit aorta. In aorta, ISF-2405 inhibited the increase in [Ca2+]cyt and muscle tension caused by norepinephrine. A Ca2+ channel blocker, verapamil, inhibited the norepinephrine-stimulated increase in [Ca2+]cyt more potently than it inhibited the increase in muscle tension, and ISF-2405 inhibited the verapamil-resistant part of the contraction. In Ca2(+)-free solution, norepinephrine induced transient increases in [Ca2+]cyt and muscle tension. ISF 2405 inhibited these changes. However, ISF-2405 did not inhibit the transient contraction induced by caffeine in the aorta. These results suggest that cadralazine is metabolized to ISF-2405 and inhibits vascular smooth muscle contraction by inhibiting receptor-mediated Ca2+ influx, Ca2+ release and Ca2+ sensitization of contractile elements. PMID- 2328761 TI - Muscarinic receptor subtype mediating vasodilation feline middle cerebral artery exhibits M3 pharmacology. AB - The nature of the muscarinic receptor subtype mediating the endothelium-dependent relaxation of the cat middle cerebral artery was investigated in vitro by recording the smooth muscle isometric tension of precontracted arterial segments. Relaxation induced by several agonists (acetylcholine (ACh), acetyl-beta methylcholine, oxotremorine, carbachol and McN-A-343) was recorded. The ability of selective (pirenzepine, dicyclomine, adiphenine, AF-DX 116, methoctramine, gallamine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and hexahydro sila-difenidol (HHSiD] and non-selective antagonists (atropine, scopolamine and quinuclidinyl benzilate (QNB] to block the relaxation induced by ACh was also estimated. The weak activity of the poorly selective M1 muscarinic receptor as together with the intermediate affinity of pirenzepine and adiphenine tend to exclude the M1 muscarinic receptor as the primary mediator of the cholinergic relaxation. The low affinity of AF-DX 116 and methoctramine further suggested that the cerebrovascular muscarinic receptor does not correspond to the M2 cardiac subtype. In contrast, 4-DAMP and HHSiD potently inhibited the ACh-induced relaxation with affinities similar to those reported at the M3 glandular receptor. We conclude that a similar to the pharmacological M3 muscarinic receptor subtype is responsible for the cholinergic relaxation of the cat middle cerebral artery. PMID- 2328762 TI - Relationship between the effects of dexamphetamine on locomotion and on striatal [3H]GBR 12783 binding in vivo. AB - In mice, low doses (1-2-4 mg/kg s.c.) of dexamphetamine stimulated locomotor activity in a dose-dependent manner. Over the same range of doses the drug dose dependently inhibited the in vivo striatal binding of the dopamine uptake inhibitor, [3H]GBR 12783. At 3 mg/kg dexamphetamine, the stimulant effect and the inhibition of the striatal binding of [3H]GBR 12783 displayed a similar time course. Pretreatments that either increased (L-DOPA 200 mg/kg, benserazide 50 mg/kg i.p.) or decreased (reserpine 5 mg/kg s.c., alpha-methyl-p-tyrosine 200 mg/kg) striatal dopamine levels did not modify the inhibition by dexamphetamine of [3H]GBR 12783 binding in vivo. This suggests that the inhibition is due to a direct effect of dexamphetamine, not mediated by endogenous dopamine, and further that a unique site is responsible for the neuronal uptake of dexamphetamine and for the binding of pure dopamine uptake inhibitors. PMID- 2328763 TI - A novel dibenzoxazepine derivative (BY-1949) increases regional cerebral blood flow. AB - The effects of BY-1949, a novel dibenzoxazepine derivative, on the regional cerebral blood flow were investigated in conscious cats. Oral administration of BY-1949 (10-50 mg/kg) significantly increased in a dose-related manner the regional cerebral blood flow in all brain regions examined. Vinpocetine (20 mg/kg p.p.) had similar effects that were shorter-lasted than those of BY-1949. From these results, it seems likely that amelioration by BY-1949 of cognitive impairment following cerebral ischemia/hypoxia or that occurs on ageing is at least partly explainable in terms of its effects on the cerebral circulation. PMID- 2328764 TI - 5-HT1 receptor agonists reduce the Ca+ component of sensory neuron action potentials. AB - Serotonin (5-HT) agonists, selective for 5-HT1, 5-HT2 or 5-HT3 receptor subtypes, were tested for their ability to mimic 5-HT in narrowing the tetraethylammonium induced calcium-dependent plateau of action potentials recorded from frog sensory neurons. 5-Carboxamidotryptamine, 5-HT, alpha-methyl 5-HT and 5-methoxy tryptamine possessed full agonist activity, with EC50S of 19 nM, 210 nM, 3.7 microM and 1.7 microM, respectively. 2-Methyl 5-HT was inactive. This agonist profile indicates that the calcium-dependent plateau in these sensory somata is modulated by a 5-HT1-like receptor. PMID- 2328765 TI - Chloroethylclonidine unmasks a non-alpha-adrenoceptor noradrenaline binding site in the rat aorta. AB - The effect of chloroethylclonidine on noradrenaline-induced contractions of the rat aorta was studied. Chloroethylclonidine (1-5 X 10(-5) M) shifted noradrenaline dose-response curve to the right approximately 5000-fold without depressing the maximum. The response to noradrenaline after chloroethylclonidine was not antagonized by phenoxybenzamine (10(-7) M), prazosin (10(-7) M), WB 4101 (10(-7) M) nor yohimbine (10(-5) M) and is therefore not mediated via alpha 1 adrenoceptors. These results would suggest that there is a homogenous population of chloroethylclonidine-sensitive alpha 1-adrenoceptors in the rat aorta and that chloroethylclonidine treatment reveals a non-alpha-adrenoceptor noradrenaline binding site in this tissue. PMID- 2328766 TI - Effect of N alpha-benzoyl-L-arginine ethyl ester on coronary perfusion pressure in isolated guinea pig heart. AB - N alpha-Benzoyl-L-arginine ethyl ester (BAEE) when compared to L-arginine significantly decreased coronary perfusion pressure of isolated guinea pig heart in a dose dependent and reproducible manner. This effect of BAEE was antagonized by haemoglobin and N-monomethyl L-arginine, both inhibitors of endothelium dependent relaxation. These results support the notion that the mechanism of relaxation elicited by BAEE is due to the generation endothelium dependent relaxing factor (EDRF) like agents. PMID- 2328767 TI - Illusory DNA breaks in quiescent lymphocytes? PMID- 2328768 TI - Persistent spreading of ligament cells on osteopontin/bone sialoprotein-I or collagen enhances tolerance to heat shock. AB - Fibronectin (FN), bone sialoprotein-I (BSP-I), Type I collagen, and a number of synthetic peptides containing the integrin attachment sequence (RDG) were evaluated for their ability to affect stress tolerance in osteo-ligament cells (OL). The attachment and spreading of OL cells was determined by the method of Klebe (1974) and Akiyama et al. (1986). Survival from heat shock was evaluated after the methods of Gerner et al. (1976). These studies showed that FN, BSP-I, and synthetic RGD peptides enhance attachment of OL cells. Increased survival from heat was limited to cells spread on fibronectin, BSP-I, and Type I collagen. OL cells that persistently spread on BSP-I and Type I collagen had more survivors than cells demonstrating transient spreading on FN. These studies indicate that (a) cell spreading is a prerequisite for stress tolerance and (b) enhanced stress tolerance is mediated by protein sequences other than those immediately surrounding the RGD sites in native proteins. PMID- 2328769 TI - A new compound which reversibly arrests T lymphocyte cell cycle near the G1/S boundary. AB - A novel cell cycle blocking agent profoundly suppressed the proliferation of mitogen-stimulated T lymphocytes. The carboxythiazole derivative arrested cells in the G1 phase of the cell cycle but did not inhibit the induction of cell surface receptors for either interleukin-2 or transferrin. The uncoupling of transferrin receptor expression from DNA synthesis indicated that a previously undefined restriction point in the cell cycle has been identified which occurs after transferrin receptor expression in late G1 and just prior to the initiation of DNA replication in S phase. T cells incubated in an inhibitory dose of the carboxythiazole derivative resumed cell cycle progression subsequent to its removal, indicating that the compound reversibly arrests cells at the late G1 restriction point. In contrast to other techniques which have been inefficient in achieving T cell synchronization, T cells released from the block mediated by the carboxythiazole compound progress through S phase with a considerable degree of synchrony. PMID- 2328770 TI - Inhibition of mitosis in fertilized sea urchin eggs by inhibition of the cyclic AMP-dependent protein kinase. AB - Inhibition of cAMP-dependent protein kinase activity by microinjection of a specific physiologic protein inhibitor into sea urchin eggs inhibits the first cleavage after fertilization. Inhibition apparently occurs at some time prior to or during formation of the mitotic spindle. Measurement of the total protein kinase activity of sea urchin egg homogenates after fertilization showed that cAMP-dependent phosphorylation increases after fertilization and then declines prior to or at the time of the first cleavage. It is concluded that a cAMP dependent phosphorylation plays a significant role in events leading to regulation of mitotic spindle assembly. PMID- 2328771 TI - The induction of vimentin gene expression by sodium butyrate in human promonocytic leukemia U937 cells. AB - The administration of 1 mM sodium butyrate induced the phenotypic differentiation of human promonocytic leukemia U937 cells, as judged by the expression of cD11b and cD11c antigens, two differentiation-specific surface markers. At the same time, butyrate greatly induced the expression at the mRNA level of the vimentin gene. The increase in the level of this RNA started at 6 h of treatment and reached the maximum at Hour 24. Such an increase was caused at least in part by a stimulation in the rate of gene transcription, as suggested by transcription assays in isolated nuclei. Experiments in the presence of cycloheximide suggested that vimentin induction is probably a direct response to the action of butyrate, not mediated by the prior induction of other gene products. Unlike the case of vimentin, the levels of other RNAs, namely beta-actin, ornithine decarboxylase, and c-myc, were not enhanced, but they decreased at different times of treatment with butyrate. Finally, we observed that butyrate induced also the differentiation of HL60 cells, another human myeloid cell type. Nevertheless, the drug failed to stimulate the expression of vimentin in this cell line. PMID- 2328772 TI - The synthesis and secretion of collagen by cultured sea urchin micromeres. AB - Circumstantial evidence in several previous studies has suggested that sea urchin embryo micromeres, the source of primary mesenchyme cells which produce the embryonic skeleton, contribute to the extracellular matrix of the embryo by synthesizing collagen. A direct test of this possibility was carried out by culturing isolated micromeres of the sea urchin Stronglyocentrotus purpuratus in artificial sea water containing 4% (v/v) horse serum. Under these conditions the micromeres divide and differentiate to produce spicules with the same timing as intact embryos. Collagen synthesis was determined by labeling cultures with [3H]proline or [35S]methionine and the medium and cell layer were assayed for collagen. The results indicate that by the second day in culture micromeres synthesize and secrete a collagenase-sensitive protein doublet with a molecular weight of about 210 kDa. Densitometry indicates a 2:1 ratio of the respective bands in the doublet which is characteristic of Type I collagen. The doublet is insensitive to digestion with pepsin. This differential sensitivity is characteristic of collagen. Over 90% of the collagen synthesized by micromeres is soluble in the seawater culture medium. On days 2-4 in culture, collagen accounts for 5% of the total protein synthesized and secreted. Additional collagenase sensitive bands are noted at 145 and 51 kDa. The relationship of the described collagen metabolism to previously characterized collagen gene expression in sea urchin embryos is discussed. PMID- 2328774 TI - Increased level of histone H1(0) messenger RNA in hypoxic Ehrlich ascites tumor cells. AB - We have investigated the expression of the H1 histone subtype H1(0) gene in Ehrlich ascites tumor cells (EAT) under varied conditions of oxygen supply. Our results show that proliferating EAT cells express H1(0) mRNA at a basal level under normoxic conditions. Severe hypoxia leads to a cessation of cell growth and causes an accumulation of cells in G1. Here, we show that the level of H1(0) histone mRNA increases within a few hours after the onset of hypoxia. PMID- 2328773 TI - Expression of the rat protamine 2 gene is suppressed at the level of transcription and translation. AB - We have compared the rat protamine 2 gene sequence (rP2) to that of the mouse protamine 2 (mP2) gene. The sequence encompasses 435 nucleotides of the coding region which includes an intron of 120 nucleotides, 461 nucleotides 5' to the coding sequence and 181 bases 3' to it. In the mouse the protamine 2 gene is abundantly transcribed and translated. The mP2 protein is initially synthesized as a precursor and then proteolytically processed to yield the mature protein. In contrast, in the rat, protamine 2 transcripts are present at 2-5% that found in the mouse and the mature protein has never been detected in spermatozoa. Although there is 92% nucleotide similarity between rat and mouse genes and 91% similarity of the predicted amino acid sequences, in vitro runoff transcription assays performed in either rat or mouse testis-derived transcription systems reveal that the rP2 promoter is only 30% as efficient a promoter as the mP2 promoter. Analyses of total sperm basic nuclear proteins extracted from epididymal sperm using a monoclonal antibody specific for protamine 2 suggest that the rat P2 mRNA is translated in vivo but is not properly processed. These results suggest that the lowered transcription rate and altered processing sites of the rat protamine 2 gene are likely to contribute to the lack of protamine 2 in rat spermatozoa. PMID- 2328775 TI - Replication of the dihydrofolate reductase genes on double minute chromosomes in a murine cell line. AB - The purpose of this study is to determine the kinetics of the replication of intrachromosomal versus extrachromosomal amplified dihydrofolate reductase (DHFR) genes. Previous studies reported that the DHFR gene, when carried intrachromosomally on a homogeneously staining region, replicates (as a unit) within the first 2 h of the S phase of the cell cycle. We wished to determine if the extrachromosomal location of the amplified genes carried on double minute chromosomes effects the timing of their replication. Equilibrium cesium chloride ultracentrifugation was used to separate newly replicated (BUdR-labeled) DNA from bulk DNA in a synchronized cell population. Hybridization with the cDNA for the DHFR gene allowed us to determine the period of time within the cell cycle in which the DHFR DNA sequences were replicated. We found that, in contrast to intrachromosomal dihydrofolate reductase genes that uniformly replicate as a unit at the beginning of the S phase of the cell cycle, dihydrofolate reductase genes carried on double minute chromosomes (DMs) replicate throughout the S phase of the cell cycle. These results suggest that control of replication of extrachromosomal DNA sequences may differ from intrachromosomal sequences. PMID- 2328776 TI - Mast cells enhance migration and proliferation of fibroblasts into an in vitro wound. AB - The effects of mast cells (MC) in an in vitro wound model were studied. The model consisted of rat peritoneal MC cultured on confluent monolayers of 3T3 fibroblasts (MC/3T3). A linear wound was performed by cutting along the midline and scraping one half of the monolayer. After 42 h fibroblasts were counted in the scraped area of the wound. In the MC/3T3 cocultures 27.6 +/- 2.1 fibroblasts were found compared to 16.6 +/- 0.9 in the 3T3 cultures. The most significant increase in the number of fibroblasts was obtained upon activation of the MC with anti-IgE antibodies immediately after wound production (39.9 +/- 2.1). Stimulation with compound 48/80 had a weaker effect (32.7 +/- 1.5). Incubation of 3T3 wounded monolayers with supernatants of anti-IgE- or compound 48/80-activated MC, or with sonicated MC, induced an increase in fibroblast number similar to that found in unactivated MC/3T3. [3H]Thymidine incorporation followed by autoradiography was performed to assess fibroblast mitosis. The highest number of labeled fibroblasts beyond the wound line was found in immunologically activated MC/3T3 (29.7 +/- 4.4), followed by compound 48/80-activated MC/3T3 (18.4 +/- 1.5), MC/3T3 (15.1 +/- 3.6), and 3T3 (10.6 +/- 2.6). After addition of aphidicolin, which inhibited fibroblast mitosis, MC were still effective in enhancing fibroblast migration. In all the cocultures MC were observed to have migrated alongside fibroblasts. Thus merely the presence of MC adhering to wounded fibroblast monolayers significantly enhanced migration and proliferation of the fibroblasts. A further increase was achieved by immunological activation of the MC. We therefore suggest that MC have a facilitating role in this in vitro wound model. PMID- 2328777 TI - Differential effects of sodium butyrate and hyperosmolality on the modulation of alkaline phosphatases of LoVo cells. AB - LoVo cells produce term-placental and intestinal alkaline phosphatases. Hyperosmolality and sodium butyrate increase the levels of both, but the effect of sodium butyrate is more pronounced on the intestinal enzyme. When applied together, induction of term-placental alkaline phosphatase is additive and that of the intestinal enzyme is synergistic. Induction by either stimulus or by their mixture is independent of cell density. However, whereas the effect of hyperosmolality is readily reversible, induction by sodium butyrate is not. No synergistic increase in intestinal alkaline phosphatase activity occurs when cells are sequentially treated with hyperosmolality and sodium butyrate or vice versa. This indicates that only when applied concurrently does one inducer amplify the effect of the other. Since the normal colonic mucosa produces intestinal alkaline phosphatase, its predominant induction by sodium butyrate in LoVo cells may reflect a more differentiated state. PMID- 2328778 TI - Differentiating effect of L-tyrosine on the human melanoma cell line IIB-MEL-J. AB - IIB-MEL-J is a highly heterogeneous newly established human melanoma cell line. The addition of 3 mM L-tyrosine to the culture medium produced (1) a great decrease in the cell growth rate, (2) a loss of the anchor-age-independent growth capacity, and (3) a change in the morphology of the cells to a fibroblastoid aspect. Coincident with these changes, an increase in subpopulations I and II and a decrease in subpopulations III and IV took place. In view of this evidence we consider that the cells have differentiated. The melanin production was not increased by the L-tyrosine treatment, suggesting that differentiation and melanin expression are not strictly correlated. PMID- 2328779 TI - Transient expression of the transformed phenotype stimulated by 12-O tetradecanoyl phorbol-13-acetate. AB - The objective of the present work was to determine whether a short-term perturbation of cells by 12-O-tetradecanoyl phorbol-13-acetate (TPA) treatment caused shape changes identical to those found in oncogenic transformation. A cell line derived from the rat respiratory tract epithelium, 1000 W, was used, in which shape changes had been identified previously as the cells underwent transformation during long-term growth in vitro. These changes corresponded to a steeper rise of the cell from the substrate and a smoothing of the surface contours throughout the periphery of the cell. The phenotype was measured by maximum likelihood estimation, based on the values of several geometrical shape descriptors. With continuous TPA treatment, the cells adopted a transformed phenotype by 2 h. The effect was maximal by 5 h but began to decline by 10 h. Shape change in the opposite direction was stimulated by treatment with the protein kinase C inhibitor staurosporine, and its effects were counteracted if the cells were simultaneously exposed to TPA. No appreciable metabolism of [20 3H]TPA occurred until 24 h after treatment. Enumerating the shape descriptors whose values composed the transformed phenotype indicated that the TPA-stimulated changes were qualitatively similar to those accompanying oncogenic transformation. The subsequent alterations, however, involved few of the variables that composed the transformed phenotype and therefore did not represent a true reversal of the change. Changes observed up to 5 h were not dependent on new RNA synthesis but required continued protein synthesis. PMID- 2328780 TI - Coordination of growth and differentiation in the fetal lung. AB - The male fetal lung begins to synthesize surfactant later in gestation than the female. This delay appears to be caused by androgens. We hypothesized that male fetal lung differentiation is delayed as a consequence of an extended phase of growth which is elicited by androgens. We observed that in vivo fetal lung protein synthesis relative to DNA synthesis peaked earlier in gestation in the female fetal lung and that this event was synchronous with the onset of differentiation. Pregnant rats were treated with dihydrotestosterone (DHT) during pregnancy, and fetal lung growth parameters were measured. Lung wet weight, dry weight, and DNA and protein concentrations were significantly elevated by DHT treatment. Type II cells and fibroblasts were isolated from lungs of DHT-treated fetuses. The number of total cells recovered was increased by 30%; the number of type II cells recovered was increased by 87%; and the number of fibroblasts recovered was increased by 42%. The type II cells which were recovered exhibited increased incorporation of [3H]thymidine into DNA and a reduced ratio of radiolabeled protein to radiolabeled DNA compared to that of cells from control lungs. Further studies were done in vitro with fibroblasts and type II cells isolated from untreated fetal rat lungs. Treatment of the fibroblasts with DHT during culture caused an increase in thymidine incorporation into DNA. This effect was not blocked by simultaneous treatment with cortisol, which normally causes reduced DNA synthesis and induces fibroblast differentiation. Treatment of the type II cells with DHT in culture caused a dose-dependent increase in cell number but a decrease in synthesis of disaturated phosphatidylcholine. These studies provide more direct evidence of the interrelationships between the control of growth and the control of differentiation in the fetal lung. DHT, a signal which delays the onset of expression of differentiation, also induces growth. We conclude that the controls of growth and of differentiation of the fetal lung are reciprocally linked. PMID- 2328781 TI - Tumor Registry Data Base. Suggestions for a systematized nomenclature of pre neoplastic and neoplastic lesions in rats. PMID- 2328782 TI - Differential effects of cigarette smoke condensate and its fractions on cultured normal and malignant human bronchial epithelial cells. AB - The differential effects of cigarette smoke condensate (CSC) and its fractions (neutral, basic, and acidic fractions) on proliferation and squamous differentiation of normal human bronchial epithelial (NHBE) cells versus human lung carcinoma cells were investigated. CSC, and the neutral and acidic fractions inhibited cellular proliferation more than the basic fraction. When compared to the acidic and basic fractions, CSC and the neural fraction were more effective in causing squamous differentiation of NHBE cells and inhibiting specific binding of phorbol dibutyrate (PDBU). There were no significant changes in ionized cytosolic calcium concentration when NHBE cells were treated with CSC. In contrast to the normal epithelial cells, neither HUT-292 nor the 3 other carcinoma cell lines examined showed marked squamous morphological changes when exposed to either CSC or its fractions and the carcinoma cells were more resistant to their inhibiting effects on cellular proliferation. These results are consistent with the hypothesis that differential effects of tobacco smoke components on cellular proliferation may allow clonal expansion of preneoplastic and neoplastic human bronchial epithelial cells during lung carcinogenesis. PMID- 2328783 TI - The early response of articular cartilage to ACL transection in a canine model. AB - Ten outbred dogs underwent unilateral transection of the anterior cruciate ligament of the knee (stifle) joint with sacrifice from 6 to 27 weeks post operatively. On the operated side were found mild degenerative changes histologically and evidence of increased proteoglycan synthesis with no net loss of uronic acid. Water content was increased in the medial femoral condyle. Contralateral knees showed evidence of increased proteoglycan synthesis and uronic acid content without histologic cartilage lesions. PMID- 2328784 TI - Dose-response study of N-nitrosomethyl(2-hydroxypropyl)amine-induced nasal cavity carcinogenesis in rats. AB - Dose response to the carcinogenic activity of N-nitrosomethyl(2 hydroxypropyl)amine (MHP) was investigated for the nasal cavity of male Wistar rats. MHP dissolved in 0.9% saline was administered intraperitoneally once a week for 12 weeks at doses of 0, 4.4, 8.8 and 17.6 mg/kg body weight, and all surviving animals were sacrificed 26 weeks after the beginning of the experiment. Hyperplasias, papillomas and squamous cell carcinomas were induced. Hyperplasias could be divided into flat, protruding and downgrowth types and were observed in respiratory and squamous epithelial regions. Papillomas and squamous cell carcinomas developed in the respiratory region, and the incidence of the latter reached 83% in rats which received the highest dose of MHP. These results indicate that MHP shows its carcinogenic activity of the nasal cavity by the development of squamous cell carcinomas. PMID- 2328785 TI - Ultrastructural study of hepatic regeneration following one-lobe, two-lobe, and subtotal hepatectomy in the rat. AB - The sequential and comparative ultrastructural features of regenerating rat liver following one-lobe, two-lobe, and subtotal hepatectomy were studied. All three groups demonstrated glycogen depletion at the 12 h post-hepatectomy interval with reaccumulation occurring at 24 h in the first two groups but not until 72 h in the subtotal hepatectomy group. Other hepatocellular alterations attributed to regenerative activity were similar in the three groups, however the onset and magnitude of those changes occurring in the two-lobe and subtotally hepatectomized rats differed significantly from those alterations occurring in the one-lobe hepatectomy group. These changes were characterized by a greater and more prolonged mitotic activity, increased proliferation of RER and smooth endoplasmic reticulum (SER), and by increased Golgi bodies. These two groups also manifested greater hepatocellular accumulation of phagolysosomes, myelin figures, and lipid bodies when compared with the one-lobe hepatectomy group. PMID- 2328786 TI - Synthesis of a 60 kD nuclear DNA binding protein induced by cytosine arabinoside in the HL 60 leukemic cell line. AB - Cytosine arabinoside (ara-C) is being employed at low dosage as differentiative rather than a cytotoxic agent in the therapy of leukemias. We have analyzed nuclear proteins from HL 60 leukemic cells treated with ara-C and have observed increased expression of a 60 kD protein in a dose-dependent fashion. This protein is actively synthesized, as assessed by labeled methionine incorporation. Using DNA cellulose affinity chromatography we could also demonstrate DNA binding properties of the 60 kD protein. PMID- 2328787 TI - Comparison of bone marrow histology in early chronic granulocytic leukemia and in leukemoid reaction. AB - A retrospective study was performed on bone marrow biopsies of 50 untreated patients with leukemoid reactions (LR) and 50 untreated patients with early chronic granulocytic leukemia (CGL). A comparison was made between hematopoietic and adipose tissues, bone and its cells, as well as other stromal components in these two disorders. Histologic and histomorphometric analyses revealed significant differences in trabecular structure, in localization of fat cells, in numbers of sinusoids, capillaries and various stromal elements. No significant differences between LR and CGL were detected in the quantity of erythro- and granulocytopoiesis and of megakaryocytes, but these were smaller in CGL than in LR. This histologic and histomorphometric evaluation demonstrates that certain histologic features may serve as valuable aids in distinguishing LR from CGL. PMID- 2328788 TI - Serum immunoreactive erythropoietin in children with acute leukaemia at various stages of disease--and the effects of treatment. AB - Most children with leukaemia are anaemic at diagnosis and at various times during treatment. Serum erythropoietin (EPO) was estimated in 27 children with acute leukaemia (n = 26) or lymphoma (n = 1) at diagnosis (n = 16), in relation to treatment with high-dose methotrexate (MTX, n = 11) or cytosine arabinoside (Ara C, n = 8), and during oral maintenance therapy (n = 10). At diagnosis, in children with anaemia serum EPO was increased, and was inversely related to haemoglobin (Hb). After treatment with high-dose MTX, in some children serum EPO increased where Hb was unchanged or increased. After treatment with high-dose Ara C, Hb declined, and serum EPO increased markedly in everyone. During oral maintenance therapy without significant anaemia, serum EPO was slightly increased in some children. In conclusion, children with leukaemia respond to anaemia with increased serum EPO concentration, but in relation to treatment with high-dose MTX and Ara-C, additional mechanisms may influence the EPO concentration. PMID- 2328789 TI - Late effects on pulmonary function of mantle-field irradiation, chemotherapy or combined modality therapy for Hodgkin's disease. AB - The aim of the present study was to assess late pulmonary sequelae after treatment for Hodgkin's disease with various treatment modalities. Pulmonary function was studied in 142 patients per median 8 years after treatment for Hodgkin's disease with mantle-field irradiation (54 patients), chemotherapy (26 patients) or mantle-field irradiation followed by chemotherapy (62 patients). Mantle-field irradiation was associated with a primary obstructive and minor restrictive lung function impairment, whereas chemotherapy and combined modality therapy were associated with a restrictive lung function impairment. The number of patients with impaired lung function and the number of patients with complaints of dyspnea, however, were almost the same in the three treatment groups. 5% of the 142 patients had a pathologically low total lung capacity, i.e. values less than 2 standard deviations below predicted values. Pathologically low values of forced vital capacity and forced expiratory volume in 1 second were seen in 33% and 27% of the patients. 33% of the smokers (n = 80) had a pathologically low diffusion capacity in contrast to 8% of the non-smokers (n = 62). Dyspnea on exertion was present in 24% of the 142 patients and was more frequent among patients with pulmonary functional abnormalities. In conclusion, late pulmonary sequelae after treatment for Hodgkin's disease do not provide a basis for choice between otherwise equally effective treatment regimes. PMID- 2328790 TI - Prognostic factors in idiopathic myelofibrosis: a simple scoring system with prognostic significance. AB - In a prognostic univariate analysis of a series of 80 patients with idiopathic myelofibrosis the Hb-concentration, the platelet count and osteomyelosclerosis emerged as factors with prognostic significance. A Hb-concentration less than 10 g/dl was associated with a significantly shorter survival than a Hb-concentration greater than or equal to 10 g/dl. A platelet count less than 100 x 10(9)/l also implied a significantly shorter survival. Patients with osteomyelosclerosis on X ray of the skeleton had a significantly better prognosis as compared to those without osteomyelosclerosis. In a multivariate regression analysis the Hb concentration consistently emerged as an important prognostic parameter, whereas the platelet count was only of prognostic significance within the first 6 months from diagnosis and the presence of osteomyelosclerosis emerged as a favourable parameter at 3 and 5 years. Based upon the above parameters and spleen size, a prognostic scoring system was designed which categorized the patients into three prognostic groups with highly different survival times (low risk group = 69 months; intermediate risk group = 33 months; high risk group = 4 months). PMID- 2328791 TI - Expression of cell-surface transferrin receptor following in vitro stimulation of peripheral blood lymphocytes in patients with beta-thalassaemia and iron deficiency anaemia. AB - The ferritin concentration in peripheral blood lymphocyte extracts was measured in 10 normal subjects, 7 patients with homozygous beta-thalassaemia, and 5 patients with iron-deficiency anaemia. The mean intracellular ferritin content was found increased in beta-thalassaemia and reduced in iron-deficient patients. Incubation of mononuclear cells in phytohaemagglutinin medium led to an increase of DNA synthesis concomitant with an increased number of lymphocytes bearing transferrin receptor and interleukin-2 receptor as measured by immunofluorescent technique. Although there was an immunological impairment of lymphocytes in patients with either iron depletion or iron loading compared to normal subjects, their ability to express transferrin receptor and interleukin-2 receptor on their cell surface was normal. PMID- 2328792 TI - The deoxyuridine suppression test in peripheral lymphocytes. AB - The effects of different deoxyuridine (dU) concentrations on lymphocytes stimulated with phytohemagglutinin (PHA) were studied for use in a lymphocyte dU suppression test (L-dUST). High concentrations of dU were necessary to overcome the unspecific spontaneous pattern of folate deficiency, dU suppression tests with cells of bone marrow (BM-dUST) and with lymphocytes were carried out in 15 patients with vitamin B-12 deficiency, in 12 with folate deficiency, and in 10 with other pathological conditions. L-dUST was also carried out in 15 healthy reference controls. The BM-dUST was able to distinguish patients with vitamin B 12 or folate acid deficiencies from those without, while the L-dUST was unable to do so in most cases. L-dUST does not, therefore, appear to be a reliable method for the diagnosis of megaloblastic changes. PMID- 2328793 TI - Glycosylated haemoglobin (HbA1c) as an index of the age of the erythrocyte population in non-diabetic patients. PMID- 2328794 TI - Hypercalcemia complicating essential thrombocythemia. PMID- 2328795 TI - [The characteristics of the temporal dynamics of stereotypic behavior in rats during chronic fenamine administration]. AB - Amphetamine-induced stereotyped behavior is a nonsteady oscillatory process. In its structure waves with 2-3, 4-5 and 10-15 minute periods may be distinguished. In some animals (30%) after chronic amphetamine administration the stereotyped behavior was attenuated with reorganization of its rhythmical pattern but in other cases (35%) stereotype on the contrary increased. Tolerance developed in the animals which had initially the more pronounced stereotype with the predomination of short-period (2-3 min) waves on the chronogram. These animals demonstrated low locomotor activity in the opened field, greater immobility in the forced swimming test and better relearning in Y-maze. PMID- 2328796 TI - [An experimental study of the psychotropic effects of aspartic acid from the aspect of age]. AB - After acute injections to adult and 90-day old rats aspartic acid in doses of 100 500 mg/kg increased the locomotor and exploratory activity during the open-field test and in a dose of 100 mg/kg exerted the antidepressant effect during the forced swimming test. Following treatment for 10 days the amino acid in a dose of 10 mg/kg disrupted acquisition of passive avoidance reaction of young rats and in a dose of 100 mg/kg inhibited learning of active avoidance reaction in adult rats. PMID- 2328797 TI - [The action of prednisolone on external respiratory function in hemorrhagic shock]. AB - The dose-dependent effect of prednisolone (30 and 60 mg/kg) on the recovery of the external respiration function and the condition of the lung tissue following hypovolemic hypotension was studied in experiments on dogs. The efficacy of prednisolone (30 mg/kg) for correction of respiratory disorders was shown. PMID- 2328798 TI - [The characteristics of gastrozepin pharmacokinetics in patients with gastric and duodenal peptic ulcers]. AB - The individual variations in the blood concentrations of gastrocepine, the period of its half-life and clearance in patients with peptic ulcers of the stomach and the duodenal bulb were determined. The patients having combined forms of peptic ulcer with chronic liver diseases exhibited most often an increase of gastrocepine half-life. A new metabolite of gastrocepine was identified by using the chromato-mass-spectral analysis. The specific antibodies to gastrocepine determining the decrease of its concentration in blood and the development of the drug resistance were found. PMID- 2328799 TI - [The effect of inducers of microsomal enzymes on glucose transport in the kidneys]. AB - Phenobarbital (50 mg/kg), benzonal (35 mg/kg) and zixorine (100 mg/kg) administered orally for 4 days and 3-methylcholanthrene (20 mg/kg) administered subcutaneously for 2 days decreased the maximal tubular transport of glucose in rats. Phenobarbital (10 mg/kg) given orally for 8-10 days reduced the tubular reabsorption of glucose in dogs. An increase of phenobarbital dose enhanced and prolonged its effect on the renal tubular transport of glucose. PMID- 2328800 TI - [The effect of oxytocin, prostenon and obzidan on uterine contractile activity in pregnant rats]. AB - The results of experimental pharmacological studies may help obstetricians to make a choice of a schedule of using the uterotropic drugs and their doses. In vivo and in vitro experiments on pregnant rats showed that administration of the Soviet-made prostaglandin E2--prostenon--in combination with oxytocin and obsidan in half doses increased its stimulating effect on the myometrium. The use of prostenon and oxytocin against the background of partusisten treatment was not followed by a significant change of their stimulating uterotropic action. PMID- 2328801 TI - [The action of the sodium salt of galbanic acid in experimental erythrocyte hyperaggregation]. AB - During in vitro experiments a sodium salt of galbanic acid was shown to prevent the development of erythrocyte hyperaggregation induced by ATP, thrombin, histamine, adrenaline and acetylcholine. In the intact organisms of dogs at preventive intravenous administration of the compound before bloodletting it prevented the development of experimental erythrocyte hyperaggregation and at administration against the background of bloodletting relieved it. PMID- 2328802 TI - [The effect of dexamethasone on the metabolism of the hormone regulators of carbohydrate metabolism in the postresuscitation period]. AB - Administration of dexamethasone (dexasone) to dogs against the background of dysfunction of the hypothalamic-pituitary-adrenal system (HPAS) developing in the first three days of the postresuscitation period causes diverse changes in secretion of hormones of the pancreas. At a relative normalization of HPAS functioning noted 7 days after resuscitation the drug was shown to decrease intensity of glycolysis and processes of lipid peroxidation. PMID- 2328803 TI - [Cytochrome P-450 induction and the subsequent induction of an immune response in rats during the chronic administration of xenobiotics]. AB - The long-term administration of xenobiotics carcinogens o-aminoazotoluene (o-AAT) and benz(a)pyrene (BP) to rats was found to cause induction of the liver cytochrome P-450 system which gradually decreases in spite of continued administration of the agents. Induction of microsomal oxygenases under these conditions is followed by induction of the immune response to o-AAT and BP. The data obtained correspond to the conception of the immunochemical functional system of homeostasis implying that the cytochrome-450 system and the immunity system are functionally linked and are elements of the common functional adaptive system of the organism. PMID- 2328804 TI - [The effect of dimephosphon on exudative and proliferative processes]. AB - The effects of dimephosphon on the models of inflammation which permitted the separation of the exudative and proliferative phases were studied on rats. The drug effect on the levels of histamine, serotonin and their precursors in blood of healthy rats was also investigated. Dimephosphon was found to exert no inhibitory influence on the proliferative reaction in contrast to the well-known non-steroidal anti-inflammatory drugs. The antihistamine activity of dimephosphon occurring on account of the intensification of histaminopexy was established. It is suggested that the antihistamine activity of dimephosphon should be used for therapeutic purposes. PMID- 2328805 TI - [The influence of the Soviet antimalarial preparation dabequin on the hemostatic system and on the anticoagulant effect of heparin]. AB - In experiments on rabbits and experiments in vitro dabechin was shown to decrease the blood coagulation status and to change the anticoagulant effect of heparin. The latter depends on the route and duration of administration of the antimalarial drug. Injections of heparin in the period of the maximal blood content of dabechin decrease the specific action of the anticoagulant. A prolonged oral administration of dabechin enhances the anticoagulant effect of heparin. During in vitro experiments the ability of dabechin to neutralize heparin with a simultaneous decrease of its specific action was shown. PMID- 2328806 TI - [The renal transport of cardiotrast, verografin and iodamide]. AB - In chronic experiments on dogs it was shown that verografin and iodamide are excreted from the body not only by filtration but by tubular excretion as well. The maximal transport of verografin and iodamide is significantly lower than that of cardiotrast. In experiments on rats similar results were obtained. Concurrent administration of verografin and iodamide with cardiotrast decreases their excretion in the urine in rats that is probably due to competition for the common transport system in the epithelium of renal tubules. PMID- 2328808 TI - [The radioprotective action of suprofen]. AB - Suprofen is a new non-steroidal anti-inflammatory drug administered intragastrically 90 min before roentgen irradiation in a dose of 20 mg/kg and then daily for 10 days in a dose of 10 mg/kg exerts the radioprotective effect evaluated according to a 30-day survival rate and an average life expectancy of the deceased animals as well as according to a decrease of postirradiation leukopenia incidence. A single administration of suprofen following roentgen irradiation exerts no radioprotective effect. Suprofen was found to enhance the radioprotective action of cysteamine. PMID- 2328807 TI - [A comparative study of the therapeutic and reactivating activities of alloxime and dipyroxime in acute poisoning of animals by organophosphate pesticides]. AB - The therapeutic and reactivating activities of a new antidote alloxime were studied as compared with dipiroxime (TMB-4) during oral intoxication of animals by chlorophos and carbophos (LD50). When administered intramuscularly in a dose of 10 mg/kg, alloxime exhibited more pronounced therapeutic and reactivating effects (particularly in the central nervous system) as compared to dipiroxime. PMID- 2328809 TI - [The clinico-pharmacological characteristics of hormonal contraceptives for enteral use]. AB - The modern clinicopharmacological data on the efficiency, mechanism of action of hormonal contraceptives, indications and contraindications for their use, possible side effects are presented. PMID- 2328810 TI - Lessons from bed number ten. PMID- 2328812 TI - Cardiac valve replacement: the homograft. PMID- 2328811 TI - White clot syndrome: a life-threatening complication of heparin therapy. AB - Nurses administering heparin should be aware that arterial or venous heparin induced thrombosis may be a paradoxical effect of the heparin itself and can result in stroke, myocardial infarction, pulmonary embolism, loss of limb, and even death. PMID- 2328813 TI - Imperatives for the future of critical care nursing. AB - In the past, nursing has tended to rely on others to predict the professional future and to suggest specific actions and strategies to make that future a reality. Each of us entered nursing practice with a vision of what the profession of nursing is. Although we may have become distracted in the interim, each of us continues to have a desired vision of the future. Critical care nursing practice can either serve as the basis for innovative leadership in the continuing evolution of autonomous nursing practice or it can continue on an evolutionary track of critical care medical practice implemented by nurses. If your vision of the future is one in which critical care nurses engage in more than the implementation of pharmaceutical and medical treatment regimens, then your vision is worth making a reality. If you believe that critical care nurses make unique and valuable patient care contributions--greater than simply retooling with every technologic advance--you need to help other nurses begin to consider your perspective. Contrary to what many people believe, the future does not just happen. Someone, whether it be a nurse, a physician, or another professional, determines by action or failure to act what the future will hold. Each nurse needs to accept responsibility for the current state of nursing. We each own a piece of nursing's future practice. I want to be sure that my piece of the future matches my vision for critical care nursing. I challenge each of you to acknowledge your vision and to begin to take action to place that vision into critical care nursing's future. PMID- 2328814 TI - An open letter to critical care nurses. PMID- 2328815 TI - Can continuous monitoring of mixed venous oxygen saturation be substituted for thermodilution cardiac output measurements? PMID- 2328816 TI - Care of the patient having radical neck surgery or permanent laryngostomy: a nursing diagnostic approach. AB - The patient who undergoes head and neck surgery requires intense nursing management for successful recovery and rehabilitation. Although several authors have presented a nursing diagnosis format care plan, none is as extensive as the one presented here. It is hoped that the preceding nursing care plan will be helpful to nurses in their management of the patient undergoing head and neck surgery. PMID- 2328817 TI - Phenylalanine hydroxylation in isolated rat kidney tubules. AB - 1. Phenylalanine hydroxylation has been demonstrated to occur in isolated rat kidney tubules under physiological conditions. 2. The hydroxylation flux response is hyperbolic with apparent Km and Vmax values of ca 85 microM phenylalanine and 49 nmol tyrosine formed/mg dry wt per hr respectively. 3. Hydroxylation in kidney tubules is substantially less sensitive to effectors of cyclic AMP turnover and Ca2+ mobilization than phenylalanine hydroxylation in isolated liver cells. PMID- 2328818 TI - Hyperthermia, unlike ionizing radiation and chemical oxidative stress, does not stimulate proteolysis in erythrocytes. AB - 1. Oxidative stress by phenazine methosulfate stimulated proteolysis in erythrocytes. 2. Gamma-irradiation of erythrocytes in the range of 50-1000 Gy also resulted in the induction of proteolysis. 3. Though it has been suggested that hyperthermia imposes an oxidative stress on a cell, hyperthermic exposure of erythrocytes (30 min, 39-49 degrees C) did not stimulate proteolysis during subsequent incubation of whole cells or hemolysates. 4. Proteolytic degradation of spectrin was accelerated during incubation of membranes isolated from cells heated above 45 degrees C but this effect seems to be due rather to thermal denaturation of spectrin than to oxidative modification of cellular proteins by hyperthermia. PMID- 2328819 TI - Differential localization of microsomal mixed function oxidase activity in periportal and perivenous hepatocytes isolated from rat liver. AB - 1. The activity per mg of microsomal protein of aminopyrine N-demethylase was higher in perivenous (PV) than in periportal (PP) hepatocytes of rat, but when it was expressed per cytochrome P-450 content the difference in the activity was not significant. 2. The activity of 7-ethoxycoumarin O-deethylase, when expressed per mg protein and per P-450 content, was significantly higher in PV than in PP cells. 3. The activities of dimethylnitrosamine(DMNA) N-demethylase and aniline p hydroxylase were not significantly different between two subpopulations of isolated hepatocytes when either expressed per mg protein or per P-450 content. PMID- 2328820 TI - Purification and characterization of anti-N lectin from Vicia unijuga leaves. AB - 1. An anti-N lectin was extracted from Vicia unijuga leaves with phosphate buffered saline (PBS). Purification of the lectin was achieved, after pretreatment of the PBS extract by ammonium sulfate fractionation and absorption with human M erythrocytes, by using a combination of conventional chromatographic techniques with asialoglycophorin AN-Sepharose CL-4B affinity chromatography. Purification steps were followed by increase of specific activity. 2. Homogeneity of the purified lectin was demonstrated by HPLC and SDS-PAGE. The purified lectin was a glycoprotein with 11.4% carbohydrate and relatively high percentages of serine, threonine and aspartic acid residues and had a Mw of 120,000 Da. 3. This lectin agglutinated human N and MN erythrocytes, but did not agglutinate M erythrocytes. Hemagglutination of the lectin was inhibited by glycophorin AN and N-active sialoglycopeptide released from human N erythrocytes by treatment with Pronase or trypsin. However, it was not inhibited by any of mono- and di saccharides, ABH-active glycoproteins, glycophorin AM and M-active sialoglycopeptide liberated from human M erythrocytes by treatment with Pronase or trypsin. PMID- 2328821 TI - Differing stabilities of snake venom cardiotoxins in acidic aqueous acetonitrile. AB - 1. Although snake venom cardiotoxins constitute a homologous family of proteins, subclasses with different structural and biological properties exist. 2. By using circular dichroism spectroscopy of twelve cardiotoxins belonging to two structural classes and one non-classified group, this investigation indicated that cardiotoxins differ in their stabilities towards denaturation in acidic aqueous acetonitrile, as used in some reversed-phase high performance liquid chromatography separations. 3. It was also shown that cardiotoxins of the structural class II are in general less stable towards this denaturation than class I and non-classified cardiotoxins. PMID- 2328822 TI - Possible existence of an intermediate pool of ubiquinone in rat heart mitochondria. AB - 1. The existence of an intermediate pool of ubiquinone in intact mitochondria of rat heart was investigated. 2. The incorporation of [3H-methyl]S adenosylmethionine into ubiquinone-9 was not influenced by the co-synthesis of the intermediate, 3-nonaprenyl-4-hydroxybenzoate. 3. In the intermediate-depleted mitochondria, the synthetic rate of the intermediate, 3-nonaprenyl-4 hydroxybenzoate was similar to that of ubiquinone. 4. The possible existence of 3 nonaprenyl-4-hydroxybenzoate as a metabolic pool under physiological condition is discussed. PMID- 2328823 TI - Purification and characterization of a novel phospholipid transfer protein from filamentous fungi. AB - 1. We have isolated from mycelia of Mucor mucedo, a filamentous fungus, a phospholipid transfer protein. 2. The purification steps were gel filtration, hydroxyapatite chromatography, blue affinity column and fast protein liquid chromatography on anion exchanger. 3. A purified protein was obtained with a molecular mass of 24 kDa and a pI of 5.05 and its N-terminal sequence was established. 4. This protein transfers phosphatidylinositol, as well as phosphatidylcholine and phosphatidylethanolamine. PMID- 2328824 TI - Prepubertal rat Sertoli cells secrete a mitogenic factor(s) that stimulates germ and somatic cell proliferation. AB - Sertoli cells were isolated from prepubertal 6- and 12-day-old rats. The Sertoli cell-conditioned media (SCCM-6 and SCCM-12) can markedly stimulate the proliferation of somatic cells and quiescent rat prespermatogonia in a dose dependent and an age-related manner. SCCM-12 stimulated cell proliferation of BALB/c 3T3 fibroblasts up to 7-fold over control values, but did not stimulate to the same degree the germ cell mitotic activity. SCCM-6 stimulated proliferation of prespermatogonia up to 5-10-fold over controls. The mitogenic factor(s) in SCCM-6 appears to be more specific to prespermatogonia than to somatic cells which is consistent with the in vivo stimulation of mitosis in germ cells 5-6 days after birth and with the action of 'mitosis inducing substance'. The mitogenic factor(s) appears to be protein with a molecular weight over 8000 and sensitive to heat and trypsin treatment. These results suggest that the different mitogenicity of prepubertal rat SCCM on germ and somatic cells may be due to secretion of multiple mitogens by Sertoli cells in an age-dependent manner. PMID- 2328825 TI - Thyroid hormone transport in a human glioma cell line. AB - The uptake of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) was studied in human glioma cells (Hs 683) and compared with that in several other neural cell lines. At 25 degrees C or 37 degrees C, total cell uptake rose rapidly and reached equilibrium within 60 min. The glioma cells had the highest uptake: 47.6 fmol of L-T3 and 43.4 fmol of L-T4 per 10(6) cells at 37 degrees C. These were inhibited 77% and 72%, respectively, by excess unlabeled hormone. Uptake in the nuclei reached equilibrium between 90 and 120 min and was also highest in glioma cells: 1.46 fmol of L-T3 and 0.49 fmol of L-T4 per 10(6) cells. When expressed as percent of total cell uptake, however, glioma cells had the lowest values (3.1% for L-T3 and 1.1% for L-T4). Also in contrast to other cell lines, glioma cells transported L-T4 almost as effectively as L-T3. D-T3 and D-T4 total cell uptake was 86% and 96% lower than that of the respective L-isomers, and the nuclear uptake as a fraction of the cell uptake was similar. Kinetic analysis of the initial rate of cell uptake gave Vmax values for D-T3 and D-T4 that were 97% and 98% lower than for the L-isomers. Antimycin and monodansylcadaverine decreased the Vmax as well as the equilibrium cell and nuclear uptake of the L-isomers. The apparent nuclear affinity constant for L-T4 in intact cells was inhibited 90% in the presence of antimycin, whereas no effect was observed in isolated nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328826 TI - Transcription factors different from the estrogen receptor stimulate in vitro transcription from promoters containing estrogen response elements. AB - The estrogen response element (ERE) directly linked to a TATA box induces CAT activity in a hormone-dependent manner in Fe 33 cells, the rat hepatoma cell line FTO-2B, stably transfected with the human estrogen receptor (ER). The same promoter construct mediates the stimulation of in vitro transcription. This stimulation is dependent on the presence of the ERE. Induction of transcription in a variety of nuclear extracts derived from mammalian cells is of the same magnitude irrespective of the presence of ER. Similarly, transcription in vitro mediated by B1 vitellogenin 5' flanking sequences in different nuclear extracts is not due to the interaction of the ER with the ERE. Competition analyses with a variety of oligonucleotides reveal that proteins different from the ER, which recognize ERE-like DNA elements, functionally interact with the ERE in vitro. These experiments suggest that ubiquitous proteins related or even identical to the transcription factor USF (MLTF) activate in vitro transcription in an ERE dependent manner. PMID- 2328827 TI - Testosterone lowers aromatase activity in cultured human genital skin fibroblasts. AB - The cytochrome P-450-dependent aromatase pathway utilizes the androgens testosterone (T) and androstenedione, as substrates for estrogen formation. In addition, androgens have been shown to influence the level of aromatase activity in various tissues. In cultured human skin fibroblasts, incubation with T for 14 h resulted in a dose-dependent decline in aromatase activity, the concentration of T producing a half-maximal decline being 6 nM. In the presence of T (50 nM), aromatase activity declined in a time-dependent fashion with maximal reduction occurring by 9 h. When aromatase kinetics were determined after preincubation of cells with T, there was a significant decline in the calculated Vmax with no significant change in the apparent Km, suggesting that incubation of cells with T reduced the number of active enzyme sites. Aromatase activity was unaffected by preincubation of cells with the synthetic androgen methyltrienolone. In addition, the decline in aromatase activity following preincubation with T was observed in cells derived from patients with complete androgen insensitivity demonstrating that the effect of T was not mediated by androgen receptors. Furthermore, new protein synthesis was not necessary for the T-mediated effect as the presence of cycloheximide (50 micrograms/ml) did not prevent it. When cells were incubated at low oxygen tension, the inhibition of aromatase activity by T was diminished. Testosterone is rapidly metabolized in genital skin fibroblasts to dihydrotestosterone, androstanedione, androsterone, 3 alpha-androstanediol, 3 beta-androstanediol and estradiol. To determine if a metabolite of T might be responsible for the repression of aromatase activity, aromatase activity was determined in cells following preincubation with various metabolites of T. Preincubation of cells with androstenedione, androstanedione or 3 alpha androstanediol produced a small but significant decline in aromatase activity, whereas preincubation of cells with dihydrotestosterone, androsterone, or 3 beta androstanediol did not have a significant effect. Aromatase activity was also unaffected by preincubation of cells with estradiol or diethylstilbestrol. When aromatase activity was assayed in microsomal preparations from cells preincubated with T, activity was reduced. Although cells preincubated with 50 nM [3H]T contained between 0.25 and 0.51 pmol of residual steroid/mg microsomal protein, the amount of [1-3H]androstenedione and T was insufficient to account for the observed decline in aromatase activity on the basis of competitive inhibition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2328828 TI - Phorbol ester receptors in bovine luteal cells: relationship to protein kinase C. AB - We investigated the binding kinetics of the tumor-promoting phorbol ester, phorbol-12,13-dibutyrate (PBt2) to dispersed total bovine luteal cells, purified small luteal cells, and purified luteal protein kinase C (PKC). Saturation analysis and competitive displacement techniques were used. Binding of [3H]PBt2 to total luteal cell preparations resulted in two distinct affinities. The high affinity component was characterized by a Kd of 4.5 +/- 1.5 nM. Analysis of [3H]PBt2 binding to total cells using competitive displacement demonstrated that the low affinity binding was specific and displaceable but dependent on concentrations of [3H]PBt2 far above the Kd for the high affinity binding. In contrast to the total cell preparations, only high affinity binding was observed in intact purified small luteal cells (Kd = 0.96 +/- 0.04 nM). Partial purification of luteal cytosolic PKC by DEAE-Sephadex chromatography resulted in co-elution of PKC enzyme activity and the [3H]PBt2 binding activity. Under conditions of saturating calcium (0.1 mM) and phosphatidylserine (PS) (100 micrograms/tube) concentrations, binding to the partially purified PKC preparation was found to be of a single high affinity and exhibited a Kd (1.3 +/- 0.2 nM) similar to the high affinity binding observed in intact cells. These results suggest that the primary phorbol ester receptor in luteal cells is PKC. However, a low affinity, high capacity [3H]PBt2 binding site also exists within the corpus luteum, either in the large cells or in the accessory cell fraction which consists mainly of endothelial cells. PMID- 2328829 TI - Distribution of estrogen and progesterone receptors and steroid-regulated gene products in the chick oviduct. AB - The distribution of estrogen and progesterone receptors (ER and PR, respectively) was studied immunohistochemically in the chick oviduct. Estrogen receptor immunoreactivity was found only in the nuclei of glandular epithelial cells. Progesterone receptor was found in the nuclei of glandular and luminal epithelia, stroma, smooth muscle cells and in the mesothelium. The dissimilar distribution of ER and PR suggests that either ER concentration in the luminal epithelium and smooth muscle is very low (below the sensitivity of ER immunostaining) or that estrogens control their PR synthesis indirectly via ER in glandular cells. A known estrogen-inducible protein, ovalbumin, was localized in the same glandular epithelial cells as ER. A progestin-inducible protein, avidin, was found in part of the luminal and glandular epithelium cells but not in other PR-positive cell types. This indicates the importance of cellular differentiation in the regulation of avidin synthesis. Estrogen and progesterone administration had effects also on ER and PR immunoreactivity. Estrogen and progesterone administrations for 24 h decreased markedly the immunoreactivity of their receptors. The decrease in receptor immunoreactivity is most likely due to a transient loss of immunoreactive receptor protein, since the antibodies (H222, PR6) react both with transformed (4 S) and non-transformed (8 S) receptor forms. At the subcellular level, PR was localized in the chromatin by immunoelectron microscopy. Progestin administration seemed to decrease PR immunoreactivity especially in the heterochromatin area, suggesting that conformational chromatin rearrangements occur during down-regulation of PR. PMID- 2328830 TI - Phorbol ester- and luteinizing hormone-induced phosphorylation of membrane proteins in bovine luteal cells. AB - In this study we have investigated the protein phosphorylation pattern in the membrane fraction prepared from bovine luteal cells. The phosphorylation reaction was carried out in vitro, under defined conditions, using either [gamma-32P]ATP or [gamma-35S]ATP as the phosphate donor. The results obtained show that [gamma 35S]ATP was a suitable phosphate donor for performing in vitro phosphorylation studies, and that thiophosphorylation of at least eight protein bands (120 kDa to 18 kDa) was observed. The extent of phosphorylation was dependent upon the duration of incubation and the amount of membrane protein used. The presence of Ca2+ was obligatory for phosphorylation and an enhanced phosphorylation was observed in the presence of Ca2+, phosphatidyl serine and phorbol 12-myristate 13 acetate (PMA), agents known to activate protein kinase C. Interestingly, when phosphorylation was carried out in the presence of luteinizing hormone (LH), a phosphorylation pattern was obtained which was similar to that obtained in the presence of calcium and phospholipid. Furthermore, in the case of two protein bands corresponding to 80-82 and 44-46 kDa, an additive phosphorylation was observed when the phosphorylation reaction was carried out for 5 min in the presence of both LH and Ca2+, phosphatidyl serine and PMA. To conclude, we have demonstrated a calcium- and phospholipid-dependent endogenous protein phosphorylation in the membrane fraction prepared from bovine luteal cells and the data obtained suggest that LH is able to stimulate this endogenous protein phosphorylation via a protein kinase C-mediated mechanism. PMID- 2328831 TI - Human growth hormone gene expression in rat but not human non-pituitary cells after stable gene transfer. AB - Tissue-specific expression of the rat growth hormone (rGH) gene requires binding of a pituitary-specific factor. Binding of this factor has been used to explain tissue-specific expression of the human growth hormone (hGH-N) gene in transfected rat pituitary (GC) tumour cells. Neither rat fibroblast (R2) nor human cervical carcinoma (HeLa) cells contain the rat pituitary-specific factor. Thus, no expression of hGH-N or rGH would be expected in these cells. R2 cell lines containing stably integrated hGH-N or rGH genes were generated. Expression of hGH-N but not rGH was detected. By contrast, stably transfected HeLa cells did not express the endogenous or transfected hGH-N genes. However, an hGH-N transcript was detected when hGH-N gene expression was directed by a viral promoter. This suggests that the block in expression occurs at the level of transcription and not mRNA stability. Hybrid genes containing 496 base pairs (bp) of hGH-N or 234 bp of rGH 5'-flanking DNA, including promoter sequences, fused to the bacterial gene coding for chloramphenicol acetyltransferase were used to stably transfect R2 cells. The hybrid hGH-N gene was more active than a promoterless construction in these cells. By contrast, the hybrid rGH gene was not. These data suggest that the hGH-N gene can be activated by rat transcription factors other than those found in pituitary cells. PMID- 2328832 TI - Cooperative enhancement at the Drosophila Sgs-3 locus. AB - The Drosophila glue gene Sgs-3 is specifically expressed in the secretory cells of the salivary glands of third instar larvae. We have assayed the expression of gene fusions to determine the role of cis-acting Sgs-3 sequences in conferring this pattern of expression. These experiments define two regulatory regions required for expression of reporter genes from the Sgs-3 promoter. One region, between 106 and 56 bp upstream of the Sgs-3 mRNA 5' end is sufficient for low but correct tissue- and stage-specific expression. A second region, lying between 629 and 130 bp 5' of the RNA start site is functionally equivalent; that is, it alone will also direct low level, specific expression. These two regions act synergistically to give high level expression. More distant upstream regions function to further increase levels of expression. These two regulatory elements can confer a salivary gland-specific pattern of expression on a heterologous promoter and are also sufficient to drive gene expression in other Drosophila species, implying conservation of regulators. PMID- 2328833 TI - Gliogenesis in rat optic nerve: astrocytes are generated in a single wave before oligodendrocytes. AB - The time of origin for astrocytes in the rat optic nerve was investigated to determine whether this cell type is generated in two waves, a first wave which occurs before the formation of oligodendrocytes and a second wave which occurs after the peak period of oligodendrocyte formation. To answer this question, multiple injections of radioactive thymidine were administered to rats after the peak period of oligodendrocyte production in the optic nerve and the animals were sacrificed several weeks after the first injection. Thymidine-labeled cells in the optic nerve were identified with the electron microscope. Of the labeled cells, greater than 80% are oligodendrocytes, 4% are microglia, 2% are astrocytes, and the remainder are unclassifiable. The thymidine-labeled cells in the nerve were not immunostained for glial fibrillary acidic protein (GFAP), a marker characteristic of astrocytes. The number of thymidine-labeled glia generated after the second postnatal week is a small fraction of the total number of glia generated neonatally. No evidence exists for a second wave of astrocyte formation in the rat optic nerve as has been suggested in a study by Miller et al. (1985, Dev. Biol. 111, 35-41); rather, the vast majority of astrocytes are generated during the first 2 postnatal weeks and these data are in keeping with classical studies of gliogenesis. The question of whether astrocytes in the rat optic nerve arise directly from division of an undifferentiated, common progenitor cell or from a cell committed to the astrocyte lineage was addressed by combining thymidine autoradiography with GFAP immunocytochemistry. Rats were sacrificed 1 hr after an injection of thymidine and their nerves were processed for GFAP immunocytochemistry and autoradiography. During the first postnatal week, many thymidine-labeled cells are immunostained for GFAP. These observations demonstrate that cells committed to the astrocyte lineage divide neonatally and give rise to additional astrocytes. PMID- 2328834 TI - Genetic dissection of a complex neurological mutant, polyhomeotic, in Drosophila. AB - Null mutations at the polyhomeotic locus of Drosophila produce a complex phenotype during embryogenesis, which includes death of the ventral epidermis, misregulation of homeotic and segmentation gene expression, and global misrouting of CNS axons. It is shown here, through the use of mosaic analyses, double mutant combinations, and in vitro culture experiments, that all aspects of the phenotype with the exception of the axonal phenotype are cell autonomous. The changes in homeotic and segmentation gene expression in the CNS are not caused by death of the ventral epidermis, but are cell autonomous effects which most likely cause changes in neuronal cell identity. The axonal phenotype associated with ph mutations is also independent of epidermal cell death, but may be due to the nonautonomous effects of altered neuronal identities or to death or transformation of some as yet unidentified cell type. Despite the apparent autonomy of the ph mutation, mutant neurons can influence the development of adjacent wild-type neurons, presumably by depriving them of their normal fasciculation partners. PMID- 2328835 TI - Repetitive DNA sequences linked to the sea urchin spec genes contain transcriptional enhancer-like elements. AB - The 5' flanking DNA of three related Strongylocentrotus purpuratus genes, Spec1, Spec2a, and Spec2c, were analyzed with respect to structure and cis-regulatory activity. The structural features of DNA sequences upstream of the first intron were highly unusual and implicated certain regions as sites of coordinate control for gene expression. By aligning the genes with a common upstream 600-bp repetitive DNA sequence element, termed RSR, it was shown that a conserved DNA block of approximately 800 bp extended from the 3' end of the first exon to the 5' end of the RSR element. In Spec2a, the conserved sequence block was a continuous stretch of DNA, but in Spec1 and Spec2c, 2.5 to 3 kb of inserted DNA bounded by short direct repeats interrupted the conserved sequence block, thus changing the relative placement of the RSR element and other 5' flanking DNA. Deletion of XhoI fragments containing the 5' half but not the 3' half of the RSR element resulted in a significant decrease in chloroamphenicolacetyl transferase (CAT) activity when Spec-CAT reporter gene fusion plasmids were injected into Lytechinus pictus eggs. These results strongly suggested, but did not prove, that the sequences held in common among the XhoI fragments, that is, the 5' half of the RSR elements, were responsible for the decrease in CAT activity. The Spec2a gene was particularly sensitive to deletions of the XhoI fragment containing the 5' half of the RSR element. The deleted element had several enhancer-like properties when inserted back into various test plasmids: it could be positioned in locations different from the transcriptional start site; in some but not all cases, it could be made to work in the reverse orientation; and it could drive expression of the CAT gene using an SV40 promoter or cryptic promoter elements. These findings suggested that an enhancer-like element important for Spec gene expression was contained within a repetitive DNA sequence. Genomic DNA blots suggested that there are many more of these RSR elements than there are Spec genes. PMID- 2328836 TI - In vitro analysis of cardiac progenitor cell differentiation. AB - Cardiac myoblast commitment and differentiation were studied in the developing avian embryo. Single cell analysis of isolated cardiogenic cells grown in vitro established that stage 4 (newly gastrulated) mesodermal cells are capable of myocyte differentiation in the absence of intercellular contact or short range cellular interactions. While cardiac myocytes derived from single isolated progenitors expressed muscle-specific myosin heavy chains (MHC), atrial and ventricular MHCs characteristic of in vivo development were not detected. When the same progenitors were grown at high density or in organ cultures, cell specific, expression of atrial and ventricular MHCs was observed, suggesting a role of cell density-dependent processes for differential MHC expression. Cardiogenic mesoderm (stages 4-8) was treated with the cocarcinogen 12-O tetradecanoylphorbol-13-acetate (TPA), maintained as organ cultures, and assayed for muscle differentiation in an attempt to identify possible stage-specific variations in cardiac progenitors. TPA irreversibly blocked the differentiation of early (stages 4-7) progenitors. When exposed to TPA, stages 4-7 cardiogenic cells failed to synthesize several muscle-specific proteins as determined by immunochemical analysis of myosin synthesis and two-dimensional gel electrophoresis of 35S-labeled proteins isolated from cardiogenic cultures. In addition, stages 4-7, TPA-treated cells did not differentiate after the withdrawal of TPA. In contrast, TPA had no effect on the expression of several muscle-specific proteins in late (stage 8) cells including the cell-specific expression of atrial and ventricular MHCs. PMID- 2328837 TI - Identification of a cadherin cell adhesion recognition sequence. AB - The molecular mechanisms by which the cadherins interact with one another to promote cell adhesion have not been elucidated. In particular, the amino acid sequences of the cadherin cell adhesion recognition sites have not been determined. Here we demonstrate that synthetic peptides containing the sequence HAV, which is common to all of the cadherins, inhibit two processes (compaction of eight-cell-stage mouse embryos and rat neurite outgrowth on astrocytes) that are known to be mediated by cadherins. The data suggest that the tripeptide HAV is a component of a cadherin cell adhesion recognition sequence. PMID- 2328838 TI - Fetal rat lung fibroblasts produce a TGF beta homolog that blocks alveolar type II cell maturation. AB - Normal growth and differentiation of the lung depends upon mesenchymal-epithelial interactions during development. Recombination experiments using immature (Day 17) and mature (Day 21) fetal rat lung fibroblasts (FRLF) revealed that the stimulatory effect of mature fibroblasts on fetal type II epithelial cells is blocked by immature fibroblasts. Similarly, conditioned medium from Day 17 FRLFs blocks the stimulatory effect (fibroblast-pneumonocyte factor) of Day 21 conditioned medium on type II epithelial cells. This blocking activity is nondialyzable, trypsin sensitive, and heat stable. Its activity is neutralized by an antibody to TGF beta, in both conditioned media and recombined cell studies, and its activity is mimicked by TGF beta. Developmentally, TGF beta-like activity is present in conditioned medium from 15- to 19-day FRLF, decreasing precipitously between 19 and 21 days gestation. Northern blot analysis of mRNAs from fetal rat lung fibroblasts on Days 17, 19, and 21 revealed expression of TGF beta at all three stages of development. PMID- 2328839 TI - Pattern regulation in the ventral histoblasts of the housefly: induction of sternal pattern abnormalities by mechanical wounding of larval epidermal cells. AB - In higher Diptera, two nests of diploid cells called the ventral histoblasts, located one on either side of each abdominal segment among the polytene larval epidermal cells, give rise to the sternite and its surrounding pleura. During metamorphosis of the insect, these two groups of cells migrate and meet with each other in the midventral region of the developing adult. The cuticular pattern elements and pigmentation in the fifth sternite of the male housefly, when compared to those of other segments as well as the tergites of both sexes, are quite distinct. The above-mentioned features, coupled with the smaller number and predictable occurrence of one of the pattern elements in this sternite, viz, the primary forceps, help one to determine the developmental potential of the histoblast nest and the regulation of its potential which occur at the time of fusion of the two contralateral nests of this segment. A simple operation of slitting the larval epidermal cells (LEC) in a hemisegment in the vicinity of the histoblast nest or extirpation or rotation of a small rectangular piece of LEC between the ventral nest and the midventral line produced pattern abnormalities including mirror image duplication in the hemisternite. An analysis of these pattern abnormalities in the different segments and, in particular, in the fifth segment provides a dynamic picture of the formation of the median sternite. Further, these abnormalities indicate the significance of the presence of the intervening pleural cells between the confronting hemisternites under experimental conditions. Thus, each of the fifth ventral nests has the developmental potential to form more than half of the final sternite pattern. Possible mechanisms for the formation of the normal median sternite during metamorphosis and for the formation of duplicated hemisternites and their fusion products under experimental conditions are discussed in light of current models of pattern regulation. PMID- 2328840 TI - Regulation of vimentin gene expression in the ocular lens. AB - Vimentin expression in the lens is striking due to the reported mesenchymal preference of vimentin and the epithelial origin of the lens. The amount of chicken vimentin mRNA levels determined by Northern blot analysis increased 3 fold from 7 to 14 days of embryonic lens development and then decreased 10-fold at 16 days of development, suggesting that post-transcriptional processes may contribute to the level of cytoplasmic vimentin mRNA during lens development. To analyze the mechanisms governing vimentin gene expression in the lens at the level of transcription, a series of chicken vimentin 5'-flanking region deletions were fused to the bacterial CAT gene and transfected into fibroblasts and lens cultures derived from three species. The -160 to +1 sequence conferred equal promoter activity in cultured chicken lens epithelial cells and fibroblasts. The 321 to -160 sequences increased promoter activity in all cultures, but more strongly in fibroblasts than in lens cells. Sequence elements in the region -608 to -321 repressed promoter activity in lens cells and fibroblasts. Promoter activity was partially restored in fibroblasts but not in lens cells by -767 to 608 sequences. Vimentin gene expression in the lens thus appears to be controlled by multiple positive- and negative-acting elements in its 5'-flanking sequence. PMID- 2328841 TI - The cholinergic neuronal differentiation factor from heart cell conditioned medium is different from the cholinergic factors in sciatic nerve and spinal cord. AB - Environmental cues play an important role in determining the transmitter phenotype of developing sympathetic neurons. Several factors have been described which can induce cholinergic function in cultured sympathetic neurons. We have compared certain biological and immunological properties of three of them, cholinergic differentiation factor (CDF), membrane-associated neurotransmitter stimulating factor (MANS), and ciliary neurotrophic factor (CNTF), to determine whether they are different. As previously reported, all three increased acetylcholine synthesis in cultured sympathetic neurons. In addition, MANS as well as CNTF and CDF decreased catecholamine synthesis. CNTF and MANS, but not CDF, promoted the survival of embryonic chick ciliary neurons. Affinity-purified antibodies raised against a synthetic peptide corresponding to the N-terminal sequence of CDF immunoprecipitated CDF, but not MANS or CNTF. These results indicate that although CDF, MANS, and CNTF have similar effects on transmitter synthesis by cultured sympathetic neurons, CDF lacks the ciliary neurotrophic activity of MANS and CNTF. Further, CDF possesses an N-terminal epitope which is absent from both MANS and CNTF. Thus, CDF is distinct from MANS and CNTF, and at least two factors exist which can alter the transmitter phenotype of sympathetic neurons in vitro. PMID- 2328842 TI - Pluripotentiality of the 2-day-old avian germinative neuroepithelium. AB - In a previous study using chick/quail chimeric embryos with homotopic transplants (Martinez & Alvarado-Mallart, 1989b), we have delimited in the 2-day-old avian embryo the areas of the neural tube giving rise to optic tectum and mesencephalic grissea as well as to isthmic grissea and cerebellum: respectively, "mesencephalic" and "metencephalic" alar plates. To investigate the determination or the competence of these areas, portions of these germinative neuroepithelia from a quail embryo were transplanted in substitution for other areas of the chick neural tube. The analysis of the chimeric brains was done by comparing alternating transverse sections stained for cytoarchitecture and with two different techniques to recognize transplanted versus host cells: either the Feulgen and Rossenbeck DNA histochemical reaction and/or immunohistochemical methods with a monoclonal antibody recognizing quail but not chick cells. The eventual visual innervation of the quail graft was analyzed in many cases by injecting anterograde axonal tracers in the eye contralateral to the graft. The results are as follows: (1) caudal metencephalon transferred to mesencephalon maintained in all cases its presumptive cerebellar phenotype, whereas (2) rostral metencephalon transferred to mesencephalon changed its fate to a tectal phenotype but maintained its cerebellar fate when transferred to diencephalon; (3) caudal mesencephalon maintained its tectal fate in 65% of the cases when transferred to diencephalon, whereas (4) rostral mesencephalon transferred to a cerebellar domain changed its fate and became influenced by the surrounding structures in all cases, but only in 85% of the cases when it was transplanted to diencephalon; (5) the in situ host diencephalon, isolated from its normal environment by a mesencephalic graft, is competent to change its fate and express a mesencephalic phenotype. These results demonstrate that at least some regions of the germinative neuroepithelium from either metencephalon, mesencephalon, and diencephalon are still pluripotent in the 2-day-old avian embryo and that their fate seems to be under the influence of the surrounding structures. Rostral mesencephalon and rostral metencephalon have been more easily influenced by environmental factors than their caudal counterparts, suggesting that regions providing instructive positional factors exist within the 2-day-old germinative neuroepithelium. These regions might play an important role in the determination of the various segments of the neural tube. PMID- 2328843 TI - Role of protein kinase C in chick embryo skeletal myoblast fusion. AB - The involvement of Ca2+ and PGE1 in myoblast fusion has been well documented. Extracellular Ca2+ is essential for myoblast adhesion, alignment, and fusion. There is an obligatory increase in Ca2+ influx immediately preceding fusion and the Ca2+ ionophore A23187 promotes precocious fusion. PGE1 receptors appear just prior to fusion, and an antagonist of PGE1 binding to cell surface receptors blocks fusion when added prior to Ca2+ influx. Finally, exogenous PGE1 induces precocious fusion. The present study was an initial test of the hypothesis that membrane protein phosphorylation by protein kinase C (PKC) links PGE1 receptor occupancy and the increase in Ca2+ influx. Our conclusion that PKC is an essential component in the regulation of myoblast fusion is based in part on the following evidence: (1) an activator of PKC, the tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA), at low concentration and for a brief exposure period, induces precocious fusion and stimulates Ca2+ influx; (2) 4 alpha-phorbol-12,13-didecanoate, an inactive analog of TPA, has no discernible effect on fusion or Ca2+ influx; (3) 1-oleoyl-2-acetyl glycerol, an analog of endogenous diacylglycerol (DAG) which activates PKC, promotes precocious fusion, as does the DAG kinase inhibitor R59022 (6-[2-[4-[(4 fluorophenyl)phenylmethylene]-1-piperidinyl]ethyl]-7- methyl-5H-thiazole-[3,2 alpha]-pyrimidin-5-one) which raises the level of endogenous DAG by inhibiting its catabolism; (4) 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a highly potent PKC inhibitor, reversibly blocks myogenesis at a point between alignment and fusion; and (5) H-7 also blocks the normal increase in Ca2+ influx preceding fusion. PMID- 2328844 TI - Relationship between haemoglobin A1C in early type 1 (insulin-dependent) diabetic pregnancy and the occurrence of spontaneous abortion and fetal malformation in Sweden. AB - This prospective nationwide study examined the relationship between diabetic control in early pregnancy as assessed by HbA1C and the incidence of spontaneous abortion and fetal malformation. HbA1C and plasma C-peptide were determined in 532 women with Type 1 (insulin-dependent) diabetes mellitus, corresponding to approximately 80% of all the diabetic pregnancies in the country during the study period 1982-1985, and 222 non-diabetic control women. Median gestational week for sampling was 9.0 in the Type 1 diabetic and 10.0 in the control group. The median value of HbA1C was 7.7% in the diabetic and 5.3% in the control group (p less than 0.001). The rates of spontaneous abortion, 7.7% vs 7.2%, and malformation, 4.3% (major 2.0%) and 2.4% (major 1.0%), were not significantly different between the diabetic and control group, respectively. These rates of malformation were not significantly different from the national figures of 4.55% (major 1.75%). Much elevated HbA1C, i.e., greater than 10.1% equal to 8 SD above the normal mean control value, was significantly associated with the occurrence of spontaneous abortion (p less than 0.001) and malformation (p less than 0.01). Discriminant analysis revealed that after correction had been made for the significant value of HbA1C to predict the occurrence of spontaneous abortion and malformation, no further predictive power was displayed by measurable plasma C-peptide, maternal age or duration of diabetes or presence of diabetic microangiopathy. We conclude that poor metabolic control in early pregnancy contributes to an increased risk of both spontaneous abortion and fetal malformation. PMID- 2328845 TI - Failure to establish islet amyloid polypeptide (amylin) as a circulating beta cell inhibiting hormone in man. AB - The presence of islet amyloid polypeptide in amyloid within pancreatic islet cells in Type 2 (non-insulin-dependent) diabetes, and its reported inhibition of glucose uptake by skeletal muscle in vitro, has prompted speculation concerning its role in the pathogenesis of diabetes. We investigated the effect of infused synthetic amidated human islet amyloid polypeptide (mol. wt. 3904, confirmed by mass spectroscopy) on intravenous glucose tolerance. Seven healthy, non-obese volunteers (age +/- SD, 27 +/- 4 years) were infused over 50 min with normal (0.9%) saline or islet amyloid polypeptide at 50 pmol.kg-1.min-1. After 20 min, a bolus of 0.5 g/kg glucose was given within 1 min and blood sampling continued for up to 60 min. Circulating concentrations of islet amyloid polypeptide reached at steady state were 1130 +/- 90 pmol/l. The calculated half-life was 11.8 +/- 0.9 min, metabolic clearance rate 5.7 +/- 0.6 ml.kg-1.min-1 and apparent distribution space therefore 94 +/- 12 ml/kg. However, islet amyloid polypeptide was found to have no effect on the peak value reached, or the total area under the curve for plasma glucose, insulin or glucagon following intravenous glucose. This study suggests circulating islet amyloid polypeptide may not be an important influence on intravenous glucose tolerance in man. PMID- 2328846 TI - Enalapril therapy in type 1 (insulin-dependent) diabetic children. PMID- 2328847 TI - Increase in electrically-stimulated Ca2+ release and suppression of caffeine response in diaphragm muscle of alloxan-diabetic mice compared with the denervation effect. AB - Changes in intracellular Ca2+ release in the diaphragm muscle of alloxan-diabetic mice were compared with changes in normal muscles and non-diabetic denervated muscles. We measured Ca2+ transient aequorin luminescence by direct electrical stimulation of these muscles. External Ca2(+)-free solution readily decreased the Ca2+ transient in normal muscles but had less of an effect in diabetic muscles. Only when the muscles were pre-injected with EGTA (reducing intracellular levels of free Ca2+) did the Ca2+ transients decrease significantly in diabetic muscles, however, there was no effect in denervated muscles. The caffeine-induced increase in Ca2+ transients, however, was delayed in both diabetic muscles and non diabetic denervated muscles. The caffeine response was observed in normal muscles under the external Ca2(+)-free conditions even after EGTA-pretreatment, whereas it was suppressed, after a brief increase, in both diabetic and non-diabetic denervated muscles. These results demonstrate (1) the insensitivity of intracellular Ca2+ mobilization to external Ca2+ levels and the ready accumulation of intracellular Ca2+ in the cytosol in the diabetic state, (2) increased permeability to Ca2+ in the denervated state and (3) impairment of the Ca2+ pool which responds to caffeine in both diabetes and the non-diabetic denervated state. Diabetic neuromyopathy thus appears to be a state of abnormal Ca2(+)-mobilization caused secondarily by high levels of blood glucose. PMID- 2328848 TI - Cellular cholesterol regulation--a defect in the type 2 (non-insulin-dependent) diabetic patient in poor metabolic control. AB - This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p less than 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels. PMID- 2328849 TI - HLA-DQB 1 codon 57 and genetic susceptibility to type 1 (insulin-dependent) diabetes mellitus in French children. AB - Variations in the incidence rate of Type 1 (insulin-dependent) diabetes mellitus might relate to ethnic-specific genetic backgrounds. HLA-DQB 1 alleles were typed in 75 French diabetic children and 85 matched control children. Enzymatically amplified DQB 1 exon 2 was hybridized with oligoprobes specific for the six most common alleles. Alleles coding for an Asp residue at position 57 in the DQ beta chain are strongly negatively associated with Type 1 diabetes in the French population. Nevertheless, one of the diabetic children was an Asp 57 homozygote (DQB 1.2/3.1). Among alleles coding for a residue other than Asp at position 57, alleles 3.2 and 2 (Ala 57) are positively associated with diabetes but not allele 1.1 (Val 57) which is less frequent in diabetic children than in control children. Heterozygosity for 2/3.2 alleles is the genotype most strongly associated with diabetes (Odds ratio = 52.9). Large comparative population studies will be necessary to determine whether the frequency of DQB 1 alleles positively associated with Type 1 diabetes (2 and 3.2) in a given ethnicity is related to its incidence rate in the same population. PMID- 2328850 TI - Which battery of cardiovascular autonomic function tests? PMID- 2328851 TI - The assessment of cardiovascular reflex activity: standardization is needed. PMID- 2328852 TI - [Pacemaker implantation in sick sinus syndrome and carotid sinus syndrome]. PMID- 2328853 TI - [Dilated cardiomyopathy. Multivariate discriminant analysis of main hemodynamic angiographic indices]. AB - The study group consisted of 47 consecutive patients (38 men and 9 women) aged between 16 and 56 years with dilated cardiomyopathy studied invasively between January 1980 and December 1986. Follow-up observation (40 +/- 29 months) showed that 28 patients were mildly symptomatic (group 1) and 19 patients were severely symptomatic (group 2: eight of them died due to intractable congestive heart failure). At univariate analysis, group 2 was characterized by higher pulmonary vascular resistance, larger end-diastolic and end-systolic left ventricular volumes, increased left ventricular mass, lower ratio of mass to volume index, depressed angiographic ejection fraction, lower ratio of end-systolic stress and peak systolic pressure to volume index. Multivariate analysis was used to determine which combination of factors might be a better effective predictor of prognosis in these patients: the most important factors were mass to volume index ratio (M/V) and end-systolic stress to volume index ratio (sigma TS/VTS). An equation was developed that can be applied to the prognosis of patients with dilated cardiomyopathy (F = 7.41573 M/V + 0.87805 sigma TS/VTS - 10.34571). A score system was devised on the basis of the summed-up value of these two parameters. When the patients were assigned (according to the score) to one of the previously mentioned two groups, the classification proved to be correct in 98% of the cases. Thus, these factors can accurately predict the development of congestive heart failure or the risk of death in patients with dilated cardiomyopathy, who are reasonable candidates for cardiac transplantation. PMID- 2328854 TI - [Nuclear magnetic resonance in congenital cardiopathies in adults]. AB - Magnetic resonance imaging is a newly developed diagnostic technique recently used for the study of the cardiovascular system. One of the most promising fields of application for magnetic resonance is the study of congenital heart diseases. Since it offers high contrast and resolution tomographic images of the heart, this technique appears particularly suitable for the anatomic assessment of cardiovascular malformations. In order to evaluate the potential of magnetic resonance imaging in the evaluation of congenital heart diseases, we reviewed 21 cases of cardiac malformations (age: 9-81, mean: 48 +/- 23). Two dimensional echo cardiography was performed on all of them. Out of the 21 patients, 13 were imaged to confirm previous diagnoses based on echocardiographic (8) or angiographic (5) data. Four more patients underwent a cardiac angiography after the magnetic resonance study. The remaining eight patients were imaged due to a poor echocardiographic examination (4) and for other reasons (4). Eight patients had an atrial septal defect, 1 had a patent foramen ovale, 2 had a ventricular septal defect, 1 had a corrected transposition of the great vessels, 2 had an aortic coarctation, 2 had a developmental venous abnormality, 5 had different congenital diseases of the aorta or of the pulmonary valve or artery. Image quality was optimal in 18 out of the 21 patients studied (85.7%). In the remaining 3 subjects image quality enabled a diagnosis. In all patients magnetic resonance imaging correctly depicted the cardiac malformation and in some cases furnished data on the severity of the disease. In 9 cases (4 atrial septal defects, 2 developmental venous abnormalities, 2 aortic aneurysms, 1 right pulmonary artery atresia) magnetic resonance imaging provided the diagnosis. These data indicate that magnetic resonance imaging may represent an important non-invasive diagnostic tool capable of offering valuable information on adult patients with suspected congenital heart disease. It is also possible to foresee that this technique will play an outstanding role as a non invasive alternative imaging technique whenever echocardiography cannot be performed is not satisfactory. Furthermore, magnetic resonance imaging should be considered a major diagnostic technique to be used for the anatomic study of the heart prior to resorting to angiography. PMID- 2328855 TI - [Mitral valve replacement in young children: a long-term follow-up]. AB - The Authors report follow-up data (mean 60, range 13-101 months) from 4 patients under two years of age (mean 11.5 months) operated on for prosthetic mitral valve implantation. Two patients were male and two female. Pre-operative diagnosis was partial atrioventricular septal defect with parachute mitral valve in one case and isolated mitral valve anomaly in the others (1 parachute, 2 hammock valves). One bioprosthesis (Liotta n. 23) and three mechanical prostheses (Bjork-Shiley) were implanted. Complications occurred in two patients: one case of endocarditis on the bioprosthesis, leading to substitution with a Bjork-Shiley valve; one case of acute thrombosis 8 months after implantation in the only pt receiving aspirin as prophylactic therapy. This complication was resolved by intravenous thrombolytic agents. All the patients are alive, in I NYHA functional class and receiving oral anti-coagulants. Instrumental follow-up with eco-Doppler demonstrated normal functioning prostheses in all the patients. A sub-aortic gradient was found in the patient with partial atrioventricular septal defect. Prosthesis-patient mismatch was identified in a patient operated on when she was 6 months old who was followed-up for 5 years. PMID- 2328856 TI - [Mitral valve replacement in young children]. PMID- 2328857 TI - [Mitral valve replacement with the Bjork-Shiley monostrut prosthesis: a 4-year clinical experience]. AB - Mitral valve replacement with Bjork-Shiley monostrut prostheses was performed in 142 patients, aged 18 to 73 (mean age: 53.8). A group of 101 patients underwent isolated mitral replacement (group A), while both mitral and aortic (in one case tricuspid) valves were replaced in 41 (group B). In 19 of group A patients and in 9 of group B patients a tricuspid annuloplasty was added. Hospital mortality was one case in each group (group A: 1%; group B:2.4%). The cause of death was low output in both cases (i.e. not valve-related). Late mortality occurred in 4 cases (4%) in group A, and in 3 cases (7.3%) in group B (follow-up: 6 to 58 months; mean follow-up: 24 months). Actuarial survival was 93.79% in group A and 89.94% in group B one year after surgery; it was 93.79% in group A and 81.76% in group B after 3 years. All deaths from undetermined causes, as well as any new unexplained neurological deficit or peripheral emboli, were considered to be valve-related: 84.18% of group A patients, as well as 67.90% of group B, were event free after 3 year (actuarial). most valve-related events occurred in the first year after surgery. We observed thromboembolism in 3 cases for each group: one patient in group B had pannus formation over the prosthetic annulus; prosthetic valve endocarditis in 1 case of group A and 2 of group B; significant hemorrhage due to anticoagulant therapy in 1 (group A); one patient in each group died suddenly, 4 and 7 months postoperatively. One group A patient and 2 group B patients were reoperated: a new valve prosthesis was implanted in two patients. Mean transvalvular gradient, as determined by echocardiography, was 3.8 +/- 2.3 (SD) mmHg in the case of isolated mitral replacement. In conclusion, we believe these results are highly encouraging, especially in the isolated mitral replacement group. Bjork-Shiley monostrut prosthesis has been demonstrated to be a reliable valve substitute, with an acceptable incidence of complications. No Bjork-Shiley monostrut prosthesis structural deterioration was seen, and its hemodynamic behaviour may be considered satisfactory. PMID- 2328858 TI - [Carotid sinus syndrome and sick sinus syndrome: 2 frequent and distinct indications for pacemaker implantation]. AB - At present, patients affected by carotid sinus syndrome and, more general by speaking, by vasovagal syncopes, are being considered more and more for pacemaker implant. However, neither the real incidence of the carotid sinus syndrome or its relation with the sick sinus syndrome with which it is often associated or even confused is precisely known. Of a total of 298 consecutive pacemaker implants, 36 (12%) were executed for carotid sinus syndrome, 33 (11%) for sick sinus syndrome and 24 (8%) for both. The annual incidence was respectively of 40, 37 and 26 implants per year/million of inhabitants. Patients affected by carotid sinus syndrome, when compared with those affected by sick sinus syndrome, showed: a higher prevalence of syncopes (97 vs 42%) more syncopal episodes per patient (2.9 +/- 2 vs 1.8 +/- 0.9), a lower prevalence of associated cardiac diseases (53 vs 100%), cardiac enlargement (36 vs 88%), heart failure (6 vs 36%) and paroxysmal atrial fibrillation (0 vs 97%), a more frequent indication to VVI pacing (75 vs 3%). Generally, when both syndromes were present, the patients showed intermediate characteristics. IN CONCLUSION: carotid sinus syndrome is a frequent indication of cardiac pacing as sick sinus syndrome; even if an association is present in about one third of patients, a distinction between carotid sinus syndrome and sick sinus syndrome is justified by theoretical and practical considerations. PMID- 2328859 TI - [A Doppler echocardiographic study of normal and dysfunctioning Carpentier Edwards bioprostheses]. AB - The aim of this study was to delineate the Doppler echocardiographic characteristics of normal and dysfunctioning Carpentier-Edwards bioprostheses. Echocardiographic and Doppler studies were performed on 61 mitral and 41 aortic valves; by means of on clinical evaluation, 15 mitral and 12 aortic valves were considered to be abnormally functioning. The maximum velocity (Vmax) of diastolic left ventricular inflow, pressure half-time and valve orifice area were assessed for prostheses in mitral position, while the maximum velocity (Vmax) of transaortic flow was calculated for prostheses in aortic position. Moreover, the quantitative assessment of mitral and/or aortic regurgitation was performed using the mapping technique with pulsed Doppler wave mode. Normally functioning mitral prostheses were characterized by Vmax less than 2.20 m/s and pressure half-time less than 164 ms; furthermore, mean values of Vmax and pressure half-time were significantly lower in normal than in dysfunctioning prostheses (1.70 +/- 0.33 vs 2.09 +/- 0.52 m/s; p less than 0.01 and 96.14 +/- 29.76 vs 147.87 +/- 57.41 ms; p less than 0.01 respectively). All dysfunctioning mitral valves were characterized by regurgitation graded as severe in 8 cases and moderate in 7 but only 40 and 20% of these presented respectively Vmax and pressure half-time values which were higher than those of normally functioning valves (2.20 m/s and 164 ms respectively); no pure stenosis was found. In the aortic position, normally functioning prostheses were characterized by Vmax less than 3.10 m/s. Furthermore, mean Vmax values were lower in normal than in dysfunctioning prostheses (2.55 +/- 0.53 vs 3.18 +/- 0.80; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328860 TI - [Silent myocardial infarct as a main manifestation of systemic lupus erythematosus]. AB - Myocardial infarction has rarely been reported in patients with systemic lupus erythematosus but may develop late in the disease usually as a result of severe and accelerated atherosclerosis or coronary arteritis. A 32-year-old man with untreated and unrecognized systemic lupus erythematosus, in the absence of conventional coronary risk factors (except family predisposition) and definite extracardiac manifestations of systemic lupus erythematosus had a silent myocardial infarction early in the course of the disease. A coronary arteriogram revealed multiple stenosis of the left anterior descending artery and critical stenosis of the right coronary artery. It is our belief that lupus vasculitis is a likely contributing factor in the development of obstructive coronary disease in this patient. PMID- 2328861 TI - [Myocardial infarct following a negative maximal exercise test: apropos of a case]. AB - A 63-year-old patient, with effort angina diagnosed 3 months previously, suffered a myocardial infarction 6 minutes after a maximal exercise stress test which had given a normal result. Intravenous streptokinase, nitrates and calcium-antagonist treatment were performed immediately, but they failed to achieve myocardial re perfusion. The patient refused coronary arteriography, but one year later underwent a further maximal exercise test, which gave a completely negative result. Here, we discuss hemodynamic mechanism likely to be involved in this rare event, and suggest that coronary arterial spasm might play an important role in inducing delayed myocardial ischemia. PMID- 2328862 TI - [Transcatheter electric ablation in ventricular tachycardia: a real alternative or a last resource?]. PMID- 2328863 TI - [Induction of atrial tachyarrhythmia in patients with Wolff-Parkinson-White syndrome with and without spontaneous atrial fibrillation]. AB - The purpose of this study was to examine the relation between spontaneous atrial fibrillation and the induction of atrial tachyarrhythmias during electrophysiologic study in patients with Wolff-Parkinson-White, with and without atrial fibrillation. Intracavitary electrophysiologic study was performed on 115 patients, 27 with spontaneous atrial fibrillation (group 1), 57 symptomatic due to AV re-entrant tachycardias, without spontaneous atrial fibrillation (group 2) and 31 asymptomatic (group 3). Induction of atrial fibrillation was attempted by using single and double atrial extrastimuli during atrial pacing at 2 different cycle lengths and by incremental atrial pacing (protocol A). When atrial fibrillation was not obtained, atrial bursts were added (protocol B). Atrial fibrillation or flutter were induced in 81% of group 1.54% of group 2 and 55% of group 3 patients (p less than 0.05), using protocol A. They were induced in 100, 75 and 71%, respectively (p = 0.01), with protocol B. Considering only sustained (greater than 1 minute) episodes, atrial fibrillation or flutter were induced in the three groups with protocol A in 74, 33 and 32% of the patients, respectively (p less than 0.001). The difference in the three groups was even greater when atrial fibrillation was considered separately from atrial flutter. The reason for this was that atrial fibrillation was induced in two thirds of group 1 patients, while only about 15% of patients without spontaneous atrial fibrillation had this arrhythmia induced. Our results suggest that the induction of sustained atrial fibrillation is a useful parameter to separate Wolff-Parkinson-White patients with from those without spontaneous atrial fibrillation. Due to the low specificity of the analysis of the shortest R-R interval during induced atrial fibrillation for the identification of the patients at risk of sudden death, the induction of sustained atrial fibrillation could be proposed as an additional parameter. This would improve the specificity of electrophysiologic study. PMID- 2328864 TI - [Evaluation of the effects of vasodilator therapy in primary pulmonary hypertension. Experience in 7 cases]. AB - Primary pulmonary hypertension is an uncommon but serious disease that often results in debilitating symptoms and early death. One approach to treatment has been to attempt a reduction of pulmonary artery pressure and vascular resistance by using vasodilator drugs with conflicting results in several studies. The aim of this study is to review the ten-years (1978-1988) experience of vasodilator therapy for primary pulmonary hypertension at our institute. In this period 7 patients, 5 women and 2 men, mean age 38.4 years (range 15-66) met clinical and hemodynamic criteria for primary pulmonary hypertension. At diagnosis 3/7 patients were in NYHA class III and 2/7 in class II. Diagnosis was confirmed by open lung biopsy in one case. Mean pulmonary artery pressure was 66 +/- 17 mmHg, mean value of pulmonary vascular resistances was 22.5 +/- 11 U.W. and of cardiac index 1.8 +/- 0.58 l/min/m2. Twelve different vasodilator drugs were tested during right heart catheterization in a non randomized manner. Various vasodilators were usually tested in the same patient (2 or more drugs in 6 patients). Only one patient did not tolerate acute therapy because of development of a persistent systemic hypotension. Hemodynamic responses to nitrates showed a general reduction in pulmonary artery pressure and pulmonary vascular resistances with marginal changes in cardiac index. Calcium channel-blocking agents elicited different responses in similar patients with favorable, little, no or adverse effects in pulmonary hemodynamics and sometimes a significant decrease in systemic vascular resistances. Also hydralazine showed favorable hemodynamic results in few cases but exacerbated pulmonary hypertension in others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328865 TI - [Vasodilators in "primary" pulmonary hypertension?]. PMID- 2328866 TI - [Post-infarction rupture of the interventricular septum. Evaluation of the main clinical parameters and postoperative survival]. AB - We reviewed 16 patients with ventricular septal rupture complicating myocardial infarction who underwent surgical repair between January 1984 and August 1987. Nine of them had anterior acute myocardial infarction (56%) and 7 inferior acute myocardial infarction (44%). The overall surgical mortality was 43.8%; in the group of patients with early treatment (less than 15 days after acute myocardial infarction) the mortality was 55%, while in the group with later treatment (16-30 days) the mortality was 28% (p-NS). Survival was unrelated to preoperative evidence of shock, magnitude of the shunt or the extent of coronary artery disease. We found a better in-hospital survival in the group of patients with ventricular septal rupture complicating anterior acute myocardial infarction (77%) vs inferior acute myocardial infarction (28%) with statistical significance (p less than 0.05). After a follow-up ranging from 1 to 40 months (mean: 17 months), 78% of the in-hospital survivors were alive and they were all in NYHA class II-III. We conclude that the major determinant of in-hospital survival in our patients was the anatomical site of acute myocardial infarction. Furthermore, we believe that the surgical repair of the ventricular septal defect is helpful in modifying the negative outcome of such an acute myocardial infarction complication. PMID- 2328867 TI - [Prognostic stratification of survivors of lst myocardial infarction: evaluation of regional kinetics and ejection fraction by bidimensional echocardiography]. AB - To determine the prognostic value of some echocardiographic indices of left ventricular function (ejection fraction, wall motion score index, left ventricular dimension) in the first year after acute myocardial infarction, we studied prospectively 162 consecutive patients (mean age: 61 +/- 11) who survived the hospital phase of a first acute myocardial infarction. Two-dimensional echocardiography was performed at hospital discharge (mean: 20 +/- 3 days after admission). For the analysis of wall motion, an 11 segment model of the left ventricle was used; from the scoring system of segmental ventricular function (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic, 5 = aneurysmal) we derived the wall motion score index (sum of assigned number to each segment/11). The echocardiographic ejection fraction was determined using the monoplane ellipsoid formula for the calculation of end diastolic and end systolic volumes in apical four-chamber and two-chamber views; the assumed ejection fraction was the mean value resulting from values of ejection fraction calculated in the two views. The follow-up was protracted from 13 to 36 months (mean: 22 months). Fourteen patients (9%) died as a result of cardiac events within 13 months of myocardial infarction. Of the patients with ejection fraction greater than or equal to 45% (81/162 = 50%) two died (first year mortality = 2.4%); of those with 35-45% ejection fraction (58/162 = 35%) two died (first year mortality = 3.5%); while of those with less than or equal to 35% ejection fraction (25/162 = 15%) ten died (first year mortality = 40%). Of the patients with wall motion score index less than 1.5 (76/162 = 47%) none died in the follow-up period; of those with score index between 1.5 and 1.9 (61/162 = 37%) four died (first year mortality = 7%); of those with score index greater than or equal to 1.9 (25/162 = 15%) ten died (first year mortality = 40%). Thus, ejection fraction and score index have the same predictive value for mortality in the first year after a first acute myocardial infarction. However, an interesting datum is that in the sub-group of patients with less than or equal to 35% ejection fraction and score index less than 1.9 the first year mortality was 15%, while in the sub-group with less than or equal to 35% but score index greater than or equal to 1.9 the first year mortality was 57%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2328868 TI - [Surgical correction of atrioventricular canal without heart catheterization]. AB - In our department, 35 patients with atrioventricular canal underwent elective surgery between June 1983 and May 1989. The diagnosis was based on clinical and echocardiographic assessment without cardiac catheterization. Nineteen patients (age 2-12 years; mean 6.6 years) had a partial atrioventricular canal and 16 (age 5-8 months; mean 7 months) presented a complete atrioventricular canal. The echocardiographic diagnosis was confirmed at surgery in all but one patient (2.8%). The latter was diagnosed as having a complete canal but at surgery a transitional canal with a restrictive ventricular septal defect was found. We based our patient selection on the natural history which excluded cases with early heart failure and pulmonary hypertension. We also relied on an accurate morphological study using two-dimensional echocardiography which excluded cases with associated cardiac malformations. Our recent experience (1986-1989) showed that 50% of the patients with complete canal and 60% of patients with partial canal underwent surgery without cardiac catheterization. PMID- 2328869 TI - [Cardiac effects of exhausting isometric muscular contraction in trained and endurance athletes]. AB - The effect of exhausting isometric contraction (60% of the maximal voluntary contraction) on left ventricular function has been investigated using echocardiography (M and B mode) in 4 groups, each of 8 subjects (27 +/- 5 years; mean +/- SD): weight lifters, 2 years of training; amateur cyclists, 4 years of training; sedentary controls, and hypertensive subjects, 1st WHO class. Heart rate, arterial pressure, ventricular diameters (diastolic and systolic), wall thickness, wall stress and the double product (heart rate x arterial pressure) were determined at rest, at exhaustion and after 30, 90 and 180 s of recovery. Maximal voluntary contraction was 48 +/- 9 kg in weight lifters; 32 +/- 5 kg in amateur cyclists; 32 +/- 4 kg in sedentary control and 36 +/- 7 kg in 1st WHO class. Exhaustion time ranged from 80 s to 120 s. Our results showed that: 1) in all subjects at exhaustion, arterial pressure and heart rate increased significantly and the index of ventricular function was decreased but not significantly; 2) after 180 s of recovery both arterial pressure and heart rate returned to the pre-exercise value; 3) wall stress was significantly lower in weight lifters than in sedentary controls; 4) the double product (index of myocardiac oxygen consumption) resulted lower in amateur cyclists that in sedentary controls. The hypertrophy of the heart could justify the slight increase in wall stress observed in weight lifters during isometric exercise. However, the low index of myocardiac oxygen consumption in amateur cyclists probably reflects the changes in cardiovascular function due to the endurance training. In hypertensive subjects, the isometric contraction causes significant and substantial increase of the wall stress and the double product. PMID- 2328870 TI - [Rupture of left ventricular pseudoaneurysm in a patient with diagnosis of unstable angina]. AB - A case of cardiac rupture with left ventricular apical pseudoaneurysm is reported. This occurred 20 days after an episode of prolonged chest pain at rest without enzymatic or electrocardiographic evidence of myocardial infarction. Prompt recognition of this condition on an echocardiogram at the onset of cardiac tamponade, with immediate angiographic confirmation enabled successful emergency surgery. PMID- 2328871 TI - [Mitral valve prolapse. A prevalence study using bidimensional echocardiography in a young population]. AB - The results of many studies on the prevalence of mitral valve prolapse have been greatly influenced by the diagnostic methods and criteria adopted as well as by population selection. The method of choice today is 2d-echocardiography because of its ability to highlight both movement anomaly (i.e. functional prolapse) and any eventual morphological variations of the mitral valve (i.e. anatomic prolapse). The latter (chordae lengthening, thickening and overabundance of the leaflets, dilation of the valvular ring) are, nowadays, considered especially important even as predictive factors of complications. Therefore we studied the prevalence of these two types of prolapse in a population of 420 university students. Functional mitral valve prolapse was found in 27/420 (6.4%) and anatomical prolapse in 2 cases (0.5%). No auscultatory finding was present in 24/27 patients with functional prolapse. There was no correlation between the two types of mitral valve prolapse and the body mass index, the fractional shortening of the left ventricle and symptoms (dyspnea, palpitations, precordial pain, dizziness). We think that the distinction between the two types of mitral valve prolapse should prove very useful for the comparison of results in future epidemiological studies. Follow-up of both groups of patients will hopefully clarify the usefulness of such distinction from the clinical point of view. PMID- 2328873 TI - [Scale of anginal pain perception during ergometric test]. PMID- 2328872 TI - [Mitral valve prolapse and the "stunned" cardiologist]. PMID- 2328874 TI - [Quantitative evaluation of left ventricular function using bidimensional echocardiography]. PMID- 2328875 TI - [Transcatheter fulguration of the atrioventricular junction in supraventricular hyperkinetic arrhythmia. Immediate and long-term results]. AB - Transcatheter direct-current ablation of the atrio-ventricular junction is a recently developed technique in the treatment of medically refractory supraventricular tachycardia. Twenty patients underwent this procedure between July 1987 and May 1989 and were followed-up for a mean period of 8.3 +/- 6 months (range 1-23). Indication for ablation included atrial flutter in 4 patients, atrial fibrillation in 8, atrial tachycardia in 1, atrio-ventricular nodal re entrant tachycardia in 4, atrioventricular re-entrant tachycardia (concealed pathway) in 2, permanent junctional reciprocating tachycardia in 1. These arrhythmias were resistant to a mean of 3.3 +/- 1.7 antiarrhythmic drugs. A mean of 1.4 +/- 0.59 (range 1-3) electrical shocks, with a mean energy of 285 +/- 135J (range 200-700), were delivered during 1-2 sessions. In all patients a persistent complete atrio-ventricular block was achieved. Immediate complications included transient hypotension in 2 pts, acute pulmonary edema in 1, premature ventricular complexes in 4, non sustained ventricular tachycardia in 4, sustained ventricular tachycardia in 1. Late complications included thrombophlebitis of the right femoral vein in 2 pts; one of them died suddenly as a result of massive pulmonary embolism 10 days after the procedure. Follow-up evaluation reveals chronic complete atrio-ventricular block in all patients. Symptoms related to pre existing arrhythmia are absent in all pts and none of them is currently taking antiarrhythmic drugs. Two patients with DDD pacing had pacemaker mediated re entrant tachycardia and 1 patient with VVIR pacing developed a pacemaker syndrome. This experience confirms that transcatheter fulguration of atrio ventricular junction is an effective technique. However, possible severe complications related to the procedure suggest this approach be restricted to patients with very symptomatic and drug-refractory supraventricular tachyarrhythmias. PMID- 2328877 TI - [Icterus caused by non-resectable neoplastic obstacle: to drain or not to drain?]. PMID- 2328876 TI - [Endocavitary transcatheter electric fulguration as a therapeutic alternative in refractory ventricular tachycardia]. AB - Three patients affected by dilated cardiomyopathy complicated by refractory ventricular tachycardia, with a high risk of sudden cardiac death, underwent transcatheter electric fulguration. The technique was applied transeptally, using the terminals of two catheter electrodes as cathode and anode. These were placed at the right and left ventricular apex, at septal level where the "critical" arrhythmia point had been identified by endocardial mapping. All patients had previously experienced more than one episode of cardiac arrest and had successfully taken several antiarrhythmic drugs. All patients presented variable morphology of ventricular tachycardia (whether spontaneous or induced). In all of them clinical tachycardia was considered as having a left bundle branch block morphology with an earlier activation at low septal level. After treatment, antiarrhythmic therapy (amiodarone 200 mg/day) was continued for all patients, although at a lower dose than before fulguration. One patient has been free from sustained ventricular tachycardia for more than two years after fulguration. In the other patients we observed an early and late arrhythmic recurrence (respectively within 1 and 8 months following fulguration) in spite of antiarrhythmic therapy. The second patient presented no further recurrence after permanent pacemaker implantation. The third patient showed an arrhythmic recurrence, with a different morphology from the previous one, concomitantly with a septic process. This technique does not appear dangerous and may be used, in highly specialized centres, on carefully selected patients as a therapeutic approach after pharmacological therapy and before automatic defibrillator implantation or surgical antiarrhythmic intervention. PMID- 2328878 TI - [Obstructive icterus in patients with hepatic tumor. Result of non-surgical biliary drainage]. AB - Seventeen patients with biliary obstruction and hepatic tumors were treated by endoscopic or percutaneous transhepatic drainage with an endoprothesis. There were 9 men and 8 women (mean age = 61 +/- 13 years). Four patients had primary hepatic carcinoma and 13 had hepatic metastases. Decrease of serum bilirubin of more than 75 percent was achieved in 12 of the patients (71 percent). The success rate was related to the level of the biliary obstacle and not to the importance of hepatic parenchymal involvement. Failure was significantly more frequent (p = 0.003) in patients with type III hilar strictures compared to the other patients with pedicular or type I and II hilar strictures. Cholangitis was the major complication (29 percent) and occurred only in the patients with type III hilar strictures. Mortality was 24 percent at 30 days. This rate was 57 percent in the group of patients with type III hilar strictures and significantly higher (p = 0.015) than other patients. Cumulative survival was better in patients with relief of jaundice than that observed in the other patients (p less than 0.01). Two patients with metastatic carcinoma of the breast treated by chemotherapy survived more than 20 months without jaundice. Analysis of these data indicates that in patients with hepatic tumors and obstructive jaundice, palliative treatment with endoprothesis can provide relief of jaundice and that prolonged survival may be observed in patients with chemosensible tumors. PMID- 2328879 TI - [Extracorporeal lithotripsy in experimental vesicular lithiasis in pigs]. AB - Experimental extracorporeal shock wave lithotripsy of gallstones was performed with the EDAP LT 01 piezoelectric lithotripter. Fragmentation of biliary stones was evaluated after implantation of human stones inside the gallbladder in 10 pigs. Lithotripsy was performed with a firing frequency of 2.5 shots per second during a mean time of 50 min. Zero to 18 days after lithotripsy, complete fragment clearance was seen in 6 cases, fragments less than 2 mm were found in 2 cases and fragments larger than 2 mm with only 1 non fragmented stone in 2 cases. There were no stone fragments in the cystic and common ducts. Damage to gallbladder and adjacent organs was appreciated after lithotripsy to the empty gallbladder of pigs with firing frequencies from 40 to 1.25 shots per second. Perforation of the gallbladder was observed in both pigs treated with a firing frequency of 40 shots per second and in 1 pig out of 3 treated with a firing frequency of 20 shots per second. With 10 shots per second and lower firing frequencies, mild histological changes of the gallbladder walls were only observed in 3 cases reoperated on the 2nd day after lithotripsy. The gallbladder wall was normal in the 5 cases reoperated on the 15th day and there were no hepatic, duodenal and pancreatic lesions. These experimental results are consistent with utilization of this machine in the treatment of gallstones in man; low firing frequencies are effective for fragmentation of gallstones without any adverse effects. PMID- 2328880 TI - [Evaluation of decontamination procedures used at digestive endoscopy units in Gironde]. AB - Decontamination procedures used for endoscopes were noted in 23 digestive endoscopy units, public and private, in the department of Gironde and compared to recommended procedures. Serial, bacteriological samples were obtained from one esogastroscope and one colonoscope in each unit, after upper endoscopy and colonoscopy diagnostic procedures at the end of the endoscopy session. Six units of 23 used complete decontamination procedures. In the 17 other units, principal errors of decontamination procedures were: inadequate cleaning of internal channel of scopes (12 units) and lack of utilization of glutaraldehyde between each endoscopy (8 units). Bacteriological samples were negative in 11/12 endoscopes after a complete decontamination procedure and in 8/39 after an inadequate procedure (p less than 0.01). Complete procedures are efficacious but not used often enough. Information and changes in endoscopic practices are necessary in digestive endoscopy units. PMID- 2328881 TI - [Preliminary results of a mass screening program for colorectal cancer]. AB - The Digestive Tumours Registry of Burgundy set up a study to assess acceptability and results of colorectal cancers screening using the Hemoccult test. A total of 95,000 people, aged 45 to 74, were included, 55,000 in 1988 and 40,000 in 1989. The aim of this paper is to report the results of the first screening process in the population tested from January to July 1988, i.e. 27,421 subjects. Information on colorectal cancer was mailed to all homes in the screening areas and a news campaign was organized. During the first 4 months, the general practitioners (GPs) either prescribed the test which was then reimbursed (Autun area), or gave it free to their patients (other areas). After that phase, the test was mailed to all subjects who had not consulted their GP, and a second letter was sent 1 month later when the test had not been sent back. A total of 14,603 subjects performed the Hemoccult test (53.3 percent). Acceptability was higher in those areas there the test was initially given free by the GPs (57.3 percent) than in those where it was prescribed (40.0 percent). Acceptability was higher in women (55.8 percent) than in men (50.6 percent). A total of 57.8 percent of the performed tests were done during the medical offer phase, 29.1 percent after mailing and 13.1 percent after the recall letter. There was a positive test in 340 subjects (2.3 percent) and 288 (84.7 percent) had colonic investigations, a colonoscopy in 99 percent of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328882 TI - Chief cell mass in normal gastric mucosa: relationship with serum pepsinogen I. AB - In the present study, a counting method for the evaluation of chief cell mass was proposed, based on the assessment of a zymogenous index (ZI) obtained by multiplying the number of cells/mm2 by the thickness of the glandular layer. Results obtained in 40 subjects with normal gastric mucosa did not show significant ZI differences between sexes. A statistically significant decrease in ZI was observed in patients above age 50, thus being directly related to the significant decrease in the thickness of the glandular parenchyma and in the number of chief cells/mm2 observed in this age group. The data obtained were in agreement with the pattern of change observed for serum pepsinogen I (PG I) whose values were related to the chief cell mass in connection with sex and age of the subjects. PMID- 2328883 TI - [Hepatic abscess complicating ileal Crohn disease in remission. Efficacy of antibiotherapy]. AB - Liver abscess is a rare complication of Crohn's disease. The authors describe a case of liver abscess associated with inactive regional enteritis which recovered completely under antibiotic treatment alone. PMID- 2328884 TI - [Acute hepatitis caused by voluntary poisoning with isoniazid]. PMID- 2328885 TI - [Rectal adenocarcinoma in association with lymphoma ("collision tumor")]. PMID- 2328886 TI - [Dysphagia and Schatzki ring: treatment using the Nd-YAG laser in 14 patients]. PMID- 2328887 TI - [Does postoperative nasogastric decompression improve the surgically treated patient's comfort? Preliminary results]. PMID- 2328888 TI - [Cancer of the esophagus and endoscopic sclerosing treatment of esophageal varices]. PMID- 2328889 TI - [Effect of Algicon suspension on postprandial esophageal pH in acid gastro esophageal reflux]. PMID- 2328890 TI - [Digestive injuries induced by the ingestion of ammonia]. PMID- 2328891 TI - [Indications for total colo-proctectomy in severe ocular complications of ulcero hemorrhagic rectocolitis]. PMID- 2328892 TI - [Spontaneous esophageal perforation: the value of various radiologic tests]. PMID- 2328893 TI - [The video-colonoscope: evaluation of its optic qualities]. PMID- 2328894 TI - [Clinical course and prognosis in T-cell lymphoblastic tumors in children typed with Soviet-produced monoclonal antibodies]. AB - Correlation analysis of the clinical course and prognosis was made in 56 children with T-cell lymphoblastic tumors (acute lymphoblastic leukemia and lymphosarcoma) typed with the use of monoclonal antibodies obtained in this country. The frequency of T-cell marker detection among all immunological subvariants in acute lymphoid leukemia and lymphosarcoma proved to be similar (36.6 and 37%, respectively). In acute lymphoid leukemia type T1 of tumor cells prevailed (58%), while in lymphosarcoma type T3 (63%). T2 and T3-cell lymphoblastic tumors were characterized by the most severe clinical course. PMID- 2328895 TI - [Immunologic correction using thymus gland preparation (T-activin) in the programmed treatment of patients with non-lymphoid leukemia]. AB - Data have been presented on the observation of 80 children with acute myeloid leukemia, among them 26 patients who, in addition to chemotherapy, were given tactivin treatment. The authors have proved the necessity of long-term tactivin administration in acute myeloid leukemia (no less than 2-3 years). that permits not only reducing the incidence of intercurrent diseases, but also increasing the duration of the remission period. PMID- 2328896 TI - [Effectiveness of oxygen-vitamin cocktails in preventing anemia, rickets, post vaccinal complications and the risk of perinatal pathology in infants]. AB - Data are presented on the composition of oxygen-vitamin cocktales used for simultaneous prevention and treatment of rickets, anemia, dystrophy, postvaccinal side effects and realization of perinatal pathology risk into a disease after birth. Mechanisms of the action of varying components of the cocktails, methods and duration of the prophylactic course, effectiveness of their use in the catamnesis have been described. PMID- 2328897 TI - [Immunocytologic structure of the lymphocyte pool in newborn infants receiving immunocorrective treatment]. AB - The study of the time course of immunocytologic structures of a lymphocyte pool in newborns with sepsis has shown a direct dependence of these parameters on the period of the disease. The lymphocyte sensitivity to thymomimetcs in the tests in vitro, as well as the level of the immunoregulatory index reflect most completely the clinical effect of these preparations, that serves an objective criterion for the use of immunocorrecting drugs in the therapy of a generalized bacterial process. PMID- 2328898 TI - [Microtests for evaluating hemostasis and their clinical value]. AB - A system of microtests, adapted for pediatric practice, has been developed, tested, and proposed for practical use. The system includes 13 microtests, 4 of them meet the requirements of a rapid diagnostic test, the others are used as differentiating and specifying. For the first time three levels of the coagulation status have been distinguished in the newborn: physiologic, border and pathologic; this enables orientation in hemorrhagic and thrombohemorrhagic diseases in the newborn. On the basis of the unified microtests the authors have determined the tactics in early diagnosis and follow-up of newborns suffering from hemorrhage treated outpatiently. The diagnosis was verified under dispensary conditions in 158 (66.6%) children with hemorrhagic diathesis. The results of the investigations described are promising for further improvement of the diagnosis and treatment of hemostasis disorders in newborns with the use of the microtests of new generation. PMID- 2328899 TI - [Treatment of acquired aplastic anemia in children with Soviet-produced antilymphocyte globulin]. AB - Soviet preparation of antilymphocytic globulin "Antilympholin" was used for the treatment of 24 children with acquired aplastic anemia. The preparation contained lymphocytotoxic antibodies and antibodies against the most important opportunistic microorganisms, thus combining the immunosuppressive and protective properties. A single dose of "Antilympholin" was 10-15 mg/kg (10-15 transfusions), the treatment course comprised 150 mg/kg. Infusion of haploidentical bone marrow was conducted in 14 children. Side effects of "Antilympholin" therapy expressed in allergic reactions were recorded in 37.4% of the patients. An early hematologic effect was achieved in 17 children (70.8%) after 1-1.5 months. It was expressed in the elimination of hemotransfusion requirement, and in the improvement of hemoglobin, platelet and neutrophil values. Hemopoietic recovery took place only in those patients who had at least minimum residual hemopoiesis. Late survival (according to Caplan-Meyer) comprised 62.1%, as compared to 30.6% in the control group of patients who received the hormonal therapy. The results of "Antilympholin" application to the treatment of children with acquired aplastic anemia have evidenced its high effectiveness which is comparable with that of foreign preparations of antilymphocytic globulin. PMID- 2328900 TI - [Characteristics of chromosomal and mitotic disorders in patients with acute non lymphoblastic leukemia exposed to chemical factors]. AB - Cytogenetic and mitotic disorders were studied in 151 patients with acute non lymphoblastic leukemia. A significant rise in the incidence of clonal disorders with predominant affection of chromosomes 5 and 7, and an increase in the percentage of cases with the presence of pathologic mitoses in hemopoietic cells have been recorded in patients who, due to their occupation, have been exposed to potentially mutagenic chemical substances. PMID- 2328901 TI - [Various morphofunctional characteristics of hematopoietic tissue in preleukemic conditions]. AB - Cultural, ultrastructural, cytochemical and histological investigations of bone marrow tissue were conducted in 26 patients with varying types of preleukemia states. A number of early structural, morphological and functional signs of hemopoietic disorders of different character and manifestation degree have been revealed. Particularly, a relationship has been established between the pathologic changes appearing in the bone marrow stroma and disorders in the morphological and functional state of the hemopoietic cells. PMID- 2328902 TI - [Stromal fibroblasts of normal bone marrow in children]. AB - Reference values of the number and proliferation index (PI) of stromal fibroblasts in children have been presented: CFUf per 10(5) = 57.0 +/- 4.1; CFUf in 1 microliters = 85.4 +/- 8.1; PI = 1.7 +/- 0.05. It has been shown that the number of stromal fibroblasts increases in the prepubertal period, especially in girls. No relationship has been observed between CFUf and the number of platelets and megakaryocytes in the children investigated. Correlation has been established between the number of bone marrow clonogenic fibroblasts and the amount of myelokaryocytes and the number of granulocytic-macrophagal precursors in the bone marrow. PMID- 2328903 TI - [Characteristic features of leukemia in infants during the first year of life]. AB - Clincocytological features of leukemia were investigated in 58 infants of the first year of life. Among these infants the sucklings present the most unfavourable group with respect to the disease prognosis. Specific clinical symptoms were most manifest in patients with congenital acute leukemia (21), and congenital chronic myeloid leukemia (20 patients). Cytogenetic investigation has revealed anomalic karyotypes (some of them are similar) in most of infants with congenital acute leukemia. In three patients with congenital chronic myeloid leukemia a typical Philadelphia chromosome has been detected, that is a rather rare case. PMID- 2328904 TI - [Characteristics of lymphocyte populations in the bone marrow and peripheral blood of children with non-T cell acute lymphoblastic leukemia during remission]. AB - Characteristics of lymphocyte populations in the bone marrow and peripheral blood were comparatively analyzed in children with non-T acute lymphoid leukemia (ALL) during remission, and in the reference group of children with conditionally normal hemopoiesis, as well as with population of lymphocytes obtained from the femur of 22-32-week fetuses. The analysis has shown pronounced changes in the children during remission. The shifts in the structure of lymphocyte population in the bone marrow of children during remission of non-T ALL are considered as compensatory, under conditions of a secondary immunodeficiency due to an abrupt diminution of the absolute number of bone marrow and circulating lymphocytes. PMID- 2328905 TI - Rapid procedure to determine the DNA base composition from small amounts of gram positive bacteria. AB - A universal rapid procedure to determine the DNA base composition (mol% guanine + cytosine) of Gram-positive bacteria is described. Cells of Gram-positive bacteria were lysed with achromo-peptidase and the mol% G + C of their DNAs were determined by using high performance liquid chromatography. One ml of a Gram positive bacterial suspension which matched MacFarland No. 3 standard turbidity was sufficient to determine the mol% G + C within 3 h. PMID- 2328906 TI - Cyclic nature of poly(3-hydroxyalkanoate) metabolism in Alcaligenes eutrophus. AB - The cyclic process of biosynthesis and degradation of poly(3-hydroxyalkanoate) (PHA) was studied in Alcaligenes eutrophus under conditions of nitrogen limitation of growth. A. eutrophus cells, which had accumulated poly(3 hydroxybutyrate) (PHB) of 55 wt% content within cells from butyric acid, were transferred into a nitrogen-free medium containing pentanoic acid as the sole carbon source and cultivated at 30 degrees C and pH 7.5. The content of PHB in A. eutrophus cells decreased with time, whereas a copolyester of 3-hydroxybutyrate (HB) and 3-hydroxyvalerate (HV) units, P(HB-co-HV), was accumulated in the presence of pentanoic acid. Conversely, when A. eutrophus cells with 50 wt% content of P(HB-co-56% HV) were incubated in a nitrogen-free medium containing butyric acid, the content of P(HB-co-56% HV) decreased with time, whereas PHB was accumulated. These results indicate the cyclic nature of PHA metabolism in A. eutrophus under these conditions. PMID- 2328907 TI - A triazine dye, cibacron blue 3G-A induces Staphylococcus aureus to form giant clusters. AB - Cibacron blue 3G-A (CB), one of the triazinyl dyes commonly used as a ligand for affinity chromatography, induced staphylococci to form giant clusters without affecting cell viability. It was demonstrated that the cluster formation was not a mechanical aggregation of cells by CB, but a consequence of its biological effect on staphylococcal growth. Clusters induced by CB did not form a regular arrangement, and were different from clusters induced by SDS or polyanethole sulfonate. PMID- 2328908 TI - Cloning and expression of the dermonecrotic toxin gene of Pasteurella multocida ssp. multocida in Escherichia coli. AB - A DNA library of Pasteurella multocida ssp. multocida strain CVI 47459 was constructed in the Lambda GEM-11 vector. Recombinant clones that encoded dermonecrotic toxin (DNT) were identified immunologically with antiserum raised against purified DNT. By comparing the DNA restriction maps of the immunoreactive recombinants, we located the DNT gene. Hybridization studies with 10 strains of P. multocida ssp. multocida suggested that strains that do not produce the DNT do not contain sequences homologous to the DNT gene. PMID- 2328909 TI - Plasmid content in Yersinia pestis strains of different origin. AB - Plasmid content in 242 Yersinia pestis strains from various natural plague foci of the U.S.S.R. and other countries was studied. Of these strains, 172 (71%) were shown to carry three plasmids described previously of about 6, 45-50 and 60 MDa, respectively. Twenty strains (8%) from different foci harboured additional cryptic plasmids, most often of about 20 mDa in size. Plasmid pPst displayed considerable constancy of its molecular mass. On the contrary, size variations of pCad (45-49 MDa) and, especially, pFra (60-190 MDa) were found. Molecular mass of these plasmids correlated with the host strain origin. PMID- 2328910 TI - Mycolyl glycolipids stimulate macrophages to release a chemotactic factor. AB - We have previously reported that mycolyl glycolipids from Nocardia rubra such as glucose or trehalose mycolates induced granuloma formation in mice. The structure of the carbohydrate moiety of the mycolyl glycolipids influenced the granuloma forming activity profoundly. Here, we have examined the macrophage-chemotactic activity in the culture supernatants stimulated with various glycolipids differing in carbohydrate moiety (trehalose 6,6'-dimycolate, or TDM; glucose monomycolate, or GM; mannose monomycolate, or MM; and fructose monomycolate, or FM). A distinctive chemotactic activity was detected with TDM or GM, but, little or none with MM or FM. PMID- 2328911 TI - Biotransformations of aromatic aldehydes by acetogenic bacteria. AB - Vanillin was subject to O demethylation and supported growth of Clostridium formicoaceticum and Clostridium thermoaceticum. Vanillin was also stimulatory to the CO-dependent growth of Peptostreptococcus productus. The aldehyde substituent of vanillin was metabolized by routes which were dependent upon both the acetogen and a co-metabolizable substrate (e.g. carbon monoxide [CO]). C. formicoaceticum and C. thermoaceticum oxidized the aldehyde group of vanillin to the carboxyl level, while P. productus reduced the aldehyde group of vanillin to the alcohol level. In contrast, during CO-dependent growth, C. thermoaceticum reduced 4 hydroxybenzaldehyde to 4-hydroxybenzyl alcohol while P. productus both reduced and oxidized 4-hydroxybenzaldehyde to 4-hydroxybenzyl alcohol and 4 hydroxybenzoate, respectively. These metabolic potentials indicate aromatic aldehydes may affect the flow of reductant during acetogenesis. PMID- 2328912 TI - Chromate-resistance in a chromate-reducing strain of Enterobacter cloacae. AB - Resistance to toxic hexavalent chromium (chromate: CrO4(2)) in Enterobacter cloacae strain HO1, isolated from an activated sludge sample, was investigated under aerobic and anaerobic conditions. Decreased uptake of 51CrO4(2-) in E. cloacae strain HO1 was observed under aerobic conditions, when compared with a standard laboratory E. cloacae strain (IAM 1624). Under anaerobic conditions E. cloacae strain HO1 was able to reduce hexavalent chromium to the less toxic trivalent form. When E. clocacae strain HO1 was grown with nitrate anaerobically, the cells were observed to lose simultaneously their chromate-reducing ability and chromate-resistance under anaerobic conditions. PMID- 2328914 TI - Long-term follow-up study of children developmentally retarded by early environmental deprivation. AB - In 1972, two children representing a case of severe developmental retardation were discovered and taken into custody. The children, an older sister (referred to as F) and a younger brother (referred to as G), were found to have achieved no more than the physical and mental age level normal to children 1 year of age or less, in spite of their actual respective chronological ages of 6 and 5. Investigation revealed that the children's developmental retardation was due both to extreme social isolation and to complex deprivation. By following their sensorimotor, linguistic, cognitive, and socio-emotional development from the time of discovery to the date of this writing, we have found that their physical and motor development or recovery has proceeded smoothly, whereas their linguistic and cognitive development has continued to show such weaknesses as defective functioning of internal speech (Vygotsky, 1962) and poor ability to deal with abstract, linguistic subjects. F and G have continued to exhibit a tendency toward undersocialization, but this has at times been rather a positive factor in the process of attaining ego identity during adolescence, especially for G, serving to protect him from unreasonable social pressures to conform to group behavior. In combination with other cases of severe deprivation, the case of F and G holds some interesting implications for theories of human development, particularly the notion of critical periods. PMID- 2328913 TI - Genetic epidemiology of bilateral breast cancer: a linkage analysis using the affected-pedigree-member method. AB - We used the affected-pedigree-member (APM) method to conduct linkage analyses on 19 pedigrees in which the probands had premenopausal bilateral breast cancer. This method analyzes all affected pairs of relatives, as opposed to siblings only, and incorporates into the analyses information on the frequency of marker alleles. Fourteen codominant marker systems were evaluated in two separate analyses. In the first, only premenopausal cases of breast cancer were coded as affected because we assumed that postmenopausal cases were due to a different etiology. In the second analysis, all cases of breast cancer were coded as affected, irrespective of menopausal status. In the premenopausal-cases-only analysis, we observed evidence suggestive of nonindependent segregation for C3 and ESD. In the all-cases analysis, we observed much weaker evidence for C3 and ESD and noted a suggestion of nonindependent segregation for AMY2 and PGM1. PMID- 2328916 TI - [Incidence of hypertension and ischemic heart disease with temporary disability among workers exposed to vibration]. AB - The article reveals the pathologic changes in man caused by vibration and detects morbidity with temporary disability (MTD), hypertension disease (HD), and ischemic heart disease (IHD) in vibration-related professions in ore extraction, metallurgic industries, etc. The morbidity data used are established on vascular tension, neuro-humoral regulation and lipid metabolism changes, and the results obtained are given in comparison with the nation-wide computerized MTD-data for 1982-1986 and those for the Communication branch. Considerably high HD and IHD incidencies have been revealed in vibration-related professions and compared to the sample branch. Computerized systems' possibilities are evaluated in MTD occupational risk-factors assessment. PMID- 2328915 TI - Between life and death: experiences of concentration camp mussulmen during the holocaust. AB - During the years of 1981 and 1982, 89 former prisoners of the Auschwitz-Birkenau concentration camp responded to questionnaires on mussulmen-prisoners in the extreme phase of starvation disease. In this article, I describe the origin of the term "mussulman," mussulmens' somatic and mental state, their behavior and camp customs. Prisoners characterized as mussulmen remain between life and death, without expressing emotional reactions and defense mechanisms apart from a hypersensibility to food-related stimuli. A mussulman was a product of the camp factory of death. A deep somatic and emotional stigma remains in those who survived the mussulmen state. PMID- 2328917 TI - [Study of the functional status of miners working in deep coal mines based on the results of mass screening]. AB - A clinical survey has been performed of 1640 miners engaged in deep mines characterized by steep geological strata, as a result of which increased disorders have been registered in audio, nervous, cardiovascular and respiratory systems. The maximum shifts of the acoustic analizer were identified in the frequency range of 4000 hertz by 10-12 years and in the speech frequency range by 14 years. Audiologic tests revealed assymmetries in auditory threshold shifts of both right and left ears in all 1640 cases studied. PMID- 2328918 TI - [Methods of medical prevention of borderline conditions and improvement in the work capacity of miners working in deep coal mines]. PMID- 2328919 TI - [Present-day metal-cutting tools and working conditions]. AB - Polyfunctional machine-tools of a processing centre type are characterized by a set of hygienic advantages as compared to universal machine-tools. But low degree of mechanization and automation of some auxiliary processes, and constructional defects which decrease the ergonomic characteristics of the tools, involve labour intensity in multi-machine processing. The article specifies techniques of allowable noise level assessment, and proposes hygienic recommendations, some of which have been introduced into practice. PMID- 2328920 TI - [Effect of ultra-high frequency electromagnetic energy on the rheologic properties of the blood]. AB - The effect of microwave radiation with the range of 8 mm (80 mVt/cm2) on rheologic blood properties was studied on 150 random-bred rats. The animals were irradiated for 5 hours a day during 3 days. It was established that the animals developed the syndrome of elevated blood viscosity. Blood hyperviscosity was detected by rotation and ultrasound viscosimeters both under low and high shift frequencies. Hematocritic index underwent no changes in exposed rats. The study revealed that microwave-induced elevation of blood viscosity was primarily caused not by hemoconcentration but by a significant decrease in erythrocyte deformability and increase in stability of the erythrocytic aggregate. Membrane damage was assumed to be one of the causes of the changes in erythrocyte rheologic properties. That assumption was confirmed by the data on the decrease of erythrocyte mechanical resistance following the exposure to microwave radiation. PMID- 2328921 TI - [Working conditions in the production of synthetic vitamin B 2]. PMID- 2328922 TI - [Separate and combined effects of chromium trioxide aerosols and noise on animals]. PMID- 2328923 TI - [Aerosol deposits in the nasopharyngeal part of the respiratory system]. PMID- 2328924 TI - [Effect of the pesticide tocuthion on the activity of microsomal cytochrome P-450 dependent monooxygenases in the rat liver]. PMID- 2328925 TI - [Periodic medical examinations of workers during annual mass screening of the population]. AB - The system of preliminary and periodic medical examinations of workers is a traditional component of the annual prophylactic medical examination of the population. The introduction of the Regulations on the latter issue makes it possible to broaden the scope and elevate the quality of prophylaxis among workers, thus to contribute to periodic examinations as part of the overall system of preventive measures. The most important problems of improving mass examinations as the first stage of the overall system, lie in the elaboration of the criteria of occupational diseases early diagnosis, adoption of uniform medical programmes for subsequent use of automation systems, as well as in a more substantial involvement of labour hygiene medical experts into current prophylactic examination programmes. PMID- 2328926 TI - The development of a sensitive analysis for 8-hydroxy-2'-deoxyguanosine. PMID- 2328927 TI - 17 beta-estradiol inhibits LDL oxidation and cholesteryl ester formation in cultured macrophages. AB - The effects of 17 beta estradiol, testosterone, the estradiol benzoate, and probucol on the oxidation kinetics of low density lipoprotein (LDL) in vitro in absorption presence of 10 microM Cu (II) are examined. Changes in the absorption at 234 nm (A234) and fluorescence (Ex340/Em420) are monitored. The kinetics of the changes observed let us suggest a precursor-product relationship between dienes and fluorochromes in the oxidized LDL. The addition of 17 beta estradiol and probucol to LDL results in a prolongation of the lag phase characterized by only insignificant formation of dienes and fluorochromes. The addition of testosterone and estradiol benzoate used as control compounds has no effect on the lag phase and thus no LDL stabilizing effect. Conditioned LDL which was incubated in F-10 medium before exposure to cultured P388D.1 macrophages increases the formation of cytoplasmic lipid droplets and of cellular cholesteryl esters. The LDL stabilizing compounds beta estradiol and probucol (but not testosterone) causes a reduction of the cholesteryl ester content of the cultured macrophages. Protection of LDL particles against oxidative damage apparently results also in lowering of cytoplasmic cholesteryl ester in cultured P388D.1 cells. We conclude that the known antiatherosclerotic potency of 17 beta estradiol may in part result from its LDL stabilizing activity. PMID- 2328928 TI - NMR analysis of low-density lipoprotein oxidatively-modified in vitro. AB - Human plasma low density lipoprotein has been oxidized at different stages in vitro and analysed by 1H, 13C, and 31P NMR spectroscopy and by biochemical methods. Information was obtained on: a) structure mobilities of lipids and on lipid-protein interactions; b) conjugated and oxo-dienes; c) polyunsaturated/monounsaturated fatty acid chains; d) lysophosphatidylcholine production. The results show that the NMR approach is particularly useful for the assessment of structural modification in oxidized LDL. PMID- 2328929 TI - [Vasodilative effects of indole alkaloids obtained from domestic plants, Uncaria rhynchophylla Miq. and Amsonia elliptica Roem. et Schult]. AB - Vasodilative effects of hirsutine (HS) and hirsuteine (HST) which were isolated from the domestic plant Uncaria rhynchophylla Miq. and beta-yohimbine (beta-Y) which was isolated from the domestic plant Amsonia elliptica Roem. et Schult. were carried out. In the hind-limb artery of anesthetized dogs, intra-arterial administration of HS, HST and beta-Y caused a vasodilatation. The vasodilative potency of HS was somewhat stronger than that of HST, and the potency of both alkaloids was approximately equal to that of papaverine. The vasodilative effect of beta-Y was similar to that of yohimbine, which is considered to be derived from its alpha-adrenoceptor blocking effect, and the potency of both alkaloids was approximately the same, while the effect of beta-Y was stronger than that of papaverine. In the coronary artery, HS showed a vasodilatation and its potency was weaker than that of papaverine. Also, HS showed the same effect in the cerebral artery, and the potency of HS was approximately the same as that of papaverine. These results suggest that the mode of the vasodilative effect induced by HS may partly differ from that of papaverine. PMID- 2328930 TI - [Effect of propiverine hydrochloride on the function of the bladder in decerebrated dogs]. AB - The effect of propiverine hydrochloride (P-4) on the function of the bladder in decerebrated dogs was compared with that of propantheline, an anticholinergic drug which is used for the treatment of micturitional disorders. P-4 (5 and 10 mg/kg, i.v.) significantly increased maximum vesical volume (Vmax); and at the dose of 10 mg/kg, i.v., it also significantly increased effective vesical volume (EV) when determined by cystometry. However, at the dose level of 2, 5 and 10 mg/kg, i.v., P-4 had no effect on residual volume (RV) after micturition contraction. Propantheline (0.25 and 0.5 mg/kg, i.v.) also significantly increased Vmax, but showed no effect on EV. At doses higher than 0.016 mg/kg, i.v., propantheline significantly increased RV. These findings indicate that P-4 is a useful drug for the treatment of pollakiuria. PMID- 2328931 TI - [Epilepsy research: three important working areas]. PMID- 2328932 TI - [Psychological disorders in epilepsy]. AB - Thirty-two patients with idiopathic grand mal, and 32 patients with psychomotor seizures were investigated for interictic mental changes. The assessment by the information provided by the patients themselves were entered into the symptom scales of the Inpatient Multidimensional Psychiatric Scale (IMPS). Some 40% of the patients, with no significant differences between the groups, reveal signs of depression in the IMPS. In comparison with available IMPS group profiles, the depressive disorder proves moderate corresponding rather to the organic or neurotic scale score than to the score achieved by patients with endogenous depression. The incidence of seizures and determinable childhood behavioral disturbances were found to be parameters that had a significant influence on the psychopathological finding, but not the duration of the condition or age at onset. PMID- 2328933 TI - [Wound management with split skin flaps--donor sites. Covering with the moist gel Geliperm]. AB - In 23 patients, donor sites of split-thickness skin grafts were treated with Geliperm Hydrogel, a swellable polyacrylamide agar. Healing duration, toleration, exudation and pain were all noted during the daily change of dressing. In 22 of the 23 cases, good healing was obtained after an average of 12.3 days. We feel that Geliperm is excellently suitable for covering the donor sites of split thickness skin grafts. PMID- 2328934 TI - [Will basic ophthalmologic management soon be obsolete? Future expectations of ophthalmologists]. PMID- 2328935 TI - Midwifery delivery choice of OB/GYN. PMID- 2328936 TI - [A case of blue rubber-bleb nevus syndrome with CAPD]. AB - The first case of blue-rubber-bleb nevus syndrome treated with CAPD in Japan was presented. As operation for A-V fistula construction could not be performed due to the skin lesions, she was obliged to have CAPD treatment. She has been visiting our hospital for regular check-ups. PMID- 2328937 TI - [Disturbance of the autonomic nerve system in patients with chronic renal failure -represented by variation coefficient of R-R intervals in the ECG as a parameter]. AB - Autonomic nerve dysfunction in patients with chronic renal failure has of late become an issue to be investigated. R-R intervals in resting electrocardiograms were measured to evaluate activities of the cardiac parasympathetic nerve system. A total of 140 patients with chronic renal failure were studied to be compared with 20 normal controls (cont.) and 39 with diabetes mellitus (DM). Of these patients 15 were subjected to conservative treatment (CRF), while 125 patients were undergoing hemodialysis due to chronic renal failure-100 of them derived from chronic glomerulonephritis (HD) and 25 from diabetes mellitus (DM.HD). The variation coefficient of the R-R interval (CVRR) was measured after the subject patients had rested for over 15 minutes before a dialysis session. The mean CVRR were 2.15 +/- 1.25% in CRF group, 2.36 +/- 1.37% in HD and 1.37 +/- 0.99% in DM.HD. These values were significantly lower than in control group (4.70 +/- 2.64%). On the other hand, the value in DM.HD group, as shown above, was significantly lower than in HD. In CRF group the CVRR values lowered as residual renal functions decreased. No significant correlations between CVRR S and the duration of hemodialysis treatment were noted among the groups. In HD group the CVRR S were significantly lower in patients with hypotensive tendency during hemodialysis than in those who enjoyed good control of blood pressure. These results suggest that the measurement of CVRR S can be of help in evaluating autonomic nerve dysfunction in patients with chronic renal failure. PMID- 2328938 TI - [Mutations in 21-hydroxylase gene caused by gene conversion-like events]. AB - Two steroid 21-hydroxylase genes (CYP21A and CYP21B) alternate in tandem with two genes for the fourth component of complement (C4A and C4B) on the short arm of chromosome 6 between the loci of HLA-B and HLA-DR. The CYP21B gene encodes an adrenal microsomal cytochrome P-450, which is specific for steroid 21 hydroxylation (P450c21). A defect of this protein would cause 21-hydroxylase deficiency, which is an autosomal recessive disease and is the most common cause of congenital adrenal hyperplasia (CAH). On the other hand, the CYP21A gene, which is homologous to the CYP21B gene up to 98% in the nucleotide sequences, is a pseudogene due to several mutations in the coding region. One of the mutations is a C----T change leading a termination codon, TAG, in the 8th exon. 1) I cloned a CYP21B gene from a patient homozygous for HLA-Bw75-DRw9 by descent. I found a C ---T change in the 8th exon of the CYP21B gene. This mutation would prevent a synthesis of 21-hydroxylase and was thought to be a crucial change to cause CAH in this patient. Because there was no apparent gross change in the organization of the C4-CYP21 region and this mutation is usually found in the CYP21A pseudogene, it seemed that a gene conversion-like event transferred the mutation from the CYP21A gene to the CYP21B gene. 2) A population study on the organization of C4-CYP21 region revealed that a reciprocal change, i.e. a T----C change in the 8th exon of the CYP21A gene, was observed in two HLA haplotypes, HLA-B44-DRw13 and HLA-Bw46-DRw8 haplotypes in Japanese population. The reciprocal changes also may be considered as a result of gene conversion-like events. PMID- 2328939 TI - [CD4+T cells restricted by DQ not by DR support CD8+T cells to grow]. AB - Much attention has been paid whether there are any differences in regulating the human immune response between HLA-DR and -DQ molecules encoded by the genes within the HLA class II multigene family. Previous studies have suggested that HLA DQ molecules control low responsiveness through activating CD4 T cells which generate CD8 positive T cells, whereas HLA -DR molecules control high responsiveness through activating CD4 helper T cells. To examine this model we investigated the streptococcal cell wall antigen (SCW) specific T cell lines restricted by either DR or DQ molecule. To identify the restricting molecules, L cell transfectants expressing DQw1, DR2AB1 or DR2AB5 from Dw12 haplotype or DQw4, DR4 or DRw53 from DW15 haplotype were used. 1. From individuals with Dw12 which is a low responder haplotype to SCW, T cell clones specific to SCW and restricted by HLA-DQw1 or DR2 were identified, whereas from individuals with Dw15 which is a high responder haplotype, only DR4 or DRw53 restricted T cell clones were identified and DQw4 restricted T cells were never observed. 2. SCW specific CD4 T cells restricted by DQw1 were able to support the growth of CD8 positive cells, whereas those restricted by DR4 could not do so. 3. The CD8 T cells also required autologous antigen presenting cells and SCW to grow, and they completely blocked the immune response to SCW in vitro. These observations clearly demonstrated the distinct function of HLA-DQ and -DR molecules in regulating the human immune response to SCW. PMID- 2328940 TI - [The effects of HLA class II genes on the susceptibility to autoimmune thyroid diseases]. AB - Immunogenetic factors such as HLA, C4, T cell receptor and immunoglobulin allotypes were investigated in 115 Japanese patients with Graves' disease. The patients showed strong positive association with HLA-A2 (R.R. = 3.45, chi 2 = 14.93, Pc less than 0.002), Bw46 (R.R. = 6.47, chi 2 = 16.25, Pc less than 0.002), Cw11 (R.R. = 4.47, chi 2 = 9.19, Pc less than 0.04) and DRw8 (R.R. = 2.22, chi 2 = 5.62, P less than 0.03, Pc: n.s.) which form one of the typical HLA haplotypes in Japanese population due to the strong linkage disequilibria. On the other hand, the patients showed negative association with HLA-B7 (R.R. = 0.15, chi 2 = 7.15), Bw52 (R.R. = 0.24, chi 2 = 7.86), DR1 (R.R. = 0.07, chi 2 = 9.71) and DQw1 (R.R. = 0.45, chi 2 = 5.62), which form HLA-B7-DR1-DQw1 and Bw52-DR2 DQw1 haplotypes. Because HLA-A2 -Bw46-Cw11-DR9 haplotype was reported to be associated with Chinese Graves' patients, and because Bw46 showed the strongest association with the Japanese patients, it was suggested that HLA class 1 antigen, Bw46, might be the primary immunogenetic factor involved in the pathogenesis of Graves' disease. Since HLA-DQw6 was reported to be associated negatively with Hashimoto's thyroiditis as same as the current observation in Graves' disease, it was suggested that HLA-DQw6 may determine the resistance to autoimmune thyroiditis. The effect of HLA-DQw6 gene, therefore, on the experimental autoimmune murine thyroiditis (EAMT) was examined, using DQw6 transgenic mouse. F1 with C3H mouse, and backcross progeny between the F1 and C3H mouse which is a susceptible strain to EAMT. The measurement of anti thyroglobulin antibody indicated that C3H mouse, (C3H x DQ-B6) F1 and backcross progeny between the F1 and C3H were high responders to the thyroglobulin, but that B6 mouse and DQ-B6 mouse were low responders. The histological examination of the thyroid gland of these mice failed to demonstrate the significant difference in susceptibility to EAMT among these mice. These results suggested that the immune response to the thyroglobulin was controlled by H-2k haplotype and that the effect of HLA-DQw6 gene on the immune response to thyroglobulin and on the autoimmune thyroiditis was marginal. PMID- 2328941 TI - [Geriatric medicine in the future]. PMID- 2328942 TI - [Pathology of HTLV-I infections]. PMID- 2328943 TI - [Aging of the eye--findings and management]. PMID- 2328944 TI - [A study of partial purification of ganglioside GD3 synthase and its enzymatic properties]. AB - A simple and rapid procedure using anion exchange chromatography was established for determinations of the activity of ganglioside GD3 synthase (CMP-NeuAc: GM3, alpha 2----8 sialyltransferase) which catalyzes the conversion of ganglioside GM3 to GD3. The procedure was applicable for determination of activity of other ganglioside synthases. With the use of this procedure and GM3-acid affinity chromatography, the GD3 synthase was partially purified about 80 fold from a Lubrol PX extract of rat liver Golgi apparatus. The enzyme obtained had a pll optimum of 6.4. The preferred acceptors of the enzyme was GM3 containing N acetylneuraminic acid (GM3 (NeuAc)) and GM3 containing N-glycolylneuraminic acid (GM3 (NeuGc)), with 2-fold higher V max in the latter than in the former. The Km values for GM3 (NeuAc), GM3 (NeuGc) and CMPNeuAc were 0.7 mM, 0.11 mM and 75 microM, respectively. The reaction product was identified as GD3 by thin layer chromatography. As to detergent, this enzyme showed maximum activity in 0.3% of Triton CF-54. The synthase did not require divalent cations for the activity, but rather Zn2+ and Cd2+ at 5 mM completely inhibited the enzyme activity. Cytidine nucleotides were strong inhibitors. The product, GD3, at 2 mM inhibited 30% the enzyme activity. The activity level of the GD3 synthase of rat liver was markedly different in rat strains, WKAH and TO strains being highest among eight strains examined. Male rat exhibited higher level than female. The synthase activity in rat liver was high at neonatal stage and decreased gradually thereafter. PMID- 2328945 TI - [Chemotherapy responsiveness of brain tumors in subrenal capsule assay]. AB - The 6-day subrenal capsule assay for determining chemotherapeutic sensitivities of brain tumors was studied. Rat glioma 9L and ACNU resistant 9L-2 were transplanted under the renal capsule of normal immunocompetent WKA rats for laboratory investigation. Evaluation of implanted tumor growth till 12 days was performed. The effects of chemotherapeutic agents administered intravenously were evaluated by measuring the growth rate of implanted tumor specimens. The results obtained from SRC were compared with the results from colony forming assay. Both were correlated to each other. On the other hand, histological investigation revealed that implanted human tumor cells had been diminished and implanted tumor was replaced by immunoreactive cells from the host in many cases. These results threw doubt on a reliability of SRC. To avoid this immunoreaction, cyclophosphamide was injected as immunosuppressive agent subcutaneously 24 hours before implantation. In such cases, the growth rates of implanted tumors were increased and histologically the implanted tumor cells existed for 6 days after implantation. Twenty-three malignant brain tumors (malignant astrocytomas 16, metastatic tumors 5, malignant lymphoma 2) were obtained as surgical specimens. Evaluable assay rate of our study were 89%. 15 patients with malignant astrocytomas were studied about correlation between the sensitivities of ACNU and post-operative clinical courses. Overall clinical correlation of 15 cases of malignant astrocytomas was 47%. These results from subrenal capsule assay are not seemed to be beneficial for clinical use. Immunoreactive response when using immunocompetent rats must be solved in future. PMID- 2328946 TI - [Purification and chemical characterization of pregnancy-specific beta 1 glycoprotein (SP1)]. AB - A pregnancy-specific beta 1-glycoprotein (SP1) was purified from human placenta using either an ion-exchange column [method I] or an anti-SP1 antibody immunoadsorbent column [method II]. The yields were 5.2% with a total of 1.2 mg per placenta [method I], and 9. 4% with a total of 2.2 mg per placenta [method II], respectively. The physicochemical properties (molecular weight, sedimentation coefficient, amino acid composition etc.) of SP1 purified from human placenta by these methods are essentially the same as those of typical SP1. It is thus apparent from the present results that these SP1 from pregnant serum and human placenta cannot be distinguished immunologically and biochemically. PMID- 2328947 TI - [Clinical application of cultured autologous epithelium to donor sites for split thickness skin graft]. AB - The present study investigated the interaction between the in situ dermis by using the donor site for split-thickness skin graft (STSG) and the cultured autologous epithelium in eleven individuals. Human epithelial cells were cultured according to the method of Rheinwald and Green, with some modification. The mirror-image site was covered by ointment dressing, and used as control. All of the grafted epithelial adhered to the wound bed within 7-8 days, and they were thick enough to be manipulated. On the other hand, the control areas didn't re epithelize until 13-18th day postoperatively. Pain and exudate were remarkably reduced in all the cases, and there was less itching in 9 cases, as compared to the control areas (P less than 0.01; sign test). Even though there was no visual difference of scarring after 3 months, the grafted areas were much softer than the control areas in 8 cases (P less than 0.01). There was also a definite difference concerning pigmentation decrease in 5 cases. 7 days post-grafting, the cultured epithelium became thicker and more differentiated in 8-10 cell layers, and a well-developed basal lamina was observed by PAS stain and on electron micrographs. A 14th day specimen from the grafted area showed almost normal epidermis with melanin granules in the basal layer, despite of a mild intercellular edema among basal and spinous cells. Biopsies after 3 months revealed that there was less dermal fibrosis in the grafted areas than in the ungrafted ones. There appeared a tendency of rapid healing associated with minimal fibrosis, leading to satisfactory results. It is possible to infer that the epithelial-dermal interaction induced by cultured epithelial autograft may influence and regulate the formation of collagen and other extracellular matrix by fibroblasts. This study suggests that cultured autologous epithelium can provide a successful permanent skin substitutes in the donor site for STSG. PMID- 2328948 TI - [Immunogenetic factors influencing HBV carrier state, the seroconversion and the development of chronic liver disease]. AB - In order to investigate the immunogenetic factors associated with hepatitis B virus (HBV) carrier state, the HBe seroconversion and the development of chronic liver disease, HLA typing were performed in 278 asymptomatic HBV carriers (ASC) and 110 patients with chronic B type hepatitis (CH). HLA typing was also performed in 178 vaccinees who had received hepatitis B vaccine. The significantly decreased frequencies of DR1 and DRw13 were found in ASC, CH and non-responders to HB vaccine. This suggests that DR1 and DRw13 may be associated with the elimination of HBV. The frequency of DR4.2 was increased in ASC, but decreased in CH. The seroconversion rate of DR4.2 positive CH as well as ASC was high. Therefore DR4.2 may have relevance to the seroconversion from HBeAg to anti HBe. PMID- 2328949 TI - [Terminal complement complex (TTC) levels in plasma and urine from glomerular diseases: enzyme-linked immunosorbent assay (ELISA) using monoclonal antibody against neoantigens of TCC]. AB - In order to get monoclonal antibodies (MoAbs) against neoantigens of terminal complement complex. MoAbs after immunization of mice with polymerized human C9 were screened for reactivities against native and polymerized C9. MoAb 1B4 reacted with tubular C9 polymer, but did not react with either native or sodium dodecyl sulfate-denatured monomeric C9 as revealed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. Moreover, MoAb 1B4 reacted with the terminal complement complex (TCC), that is, membrane attack complex and the fluid-phase SC5b-9 complex. Thus, MoAb 1B4 recognized a neoantigen in the moiety of C9 polymer in the TCC. Thereafter, we measured TCC in plasma and urine with sandwich ELISA using 1B4 and antihuman C7 antibody to evaluate terminal complement activation in patients with glomerular diseases. TCC was detectable in plasma but not in urine from most of normal controls. In plasma, TCC was elevated in 5 of 23 with lupus nephritis and in 6 of 11 with membranoproliferative glomerulonephritis, but all patients with IgA nephritis, focal glomerulosclerosis, membranous glomerulonephritis and minimal change lesions (MC) showed normal levels. In urine, TCC was detectable in most of patients with severe proteinuria (greater than or equal to 100 mg/dl) except MC. The TCC present in urine was partially purified by gel filtration with Sepharose 6B and was found to contain C5, C6, C7, C8, C9, and S protein by ELISA. Although the molecular weight of SC5b-9 complex is similar to IgM, fractional excretion rate of TCC was about 100 times higher than that of IgM. These results suggest that urinary TCC contains SC5b-9 complex like plasma TCC and is mostly derived from renal origin. PMID- 2328950 TI - Isolation of a potent cholesterol nucleation-promoting activity from human gallbladder bile: role in the pathogenesis of gallstone disease. AB - Gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity was found in gallbladder bile from cholesterol gallstone patients but also in gallbladder bile from patients without stones and patients with pigment stones. Bile from patients with multiple cholesterol gallstones contained high concanavalin A-binding nucleation-promoting activity. The activity was much lower in bile samples from pigment stone patients, patients without stones and patients with a solitary cholesterol stone. Serum contained very little activity and no concanavalin A-binding nucleation-promoting activity could be demonstrated in gallbladder mucosa. This suggests that concanavalin A binding nucleation promoter is produced in the liver or bile duct epithelium. The activity was fully resistant to digestion with pronase but was heat labile and could be destroyed by prolonged incubation with a mixed glycosidase preparation indicating that sugar residues are important for this activity. On a Superose 12 gel permeation column, promoting activity eluted in two major peaks at apparent molecular weights of 150 +/- 30 kD (n = 5) and less than 5 kD respectively. The mobility on the column was not influenced by pronase digestion. The factor with the higher molecular weight could be isolated further by polyacrylamide gel electrophoresis under nondenaturing conditions. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the apparent molecular weight of the glycoprotein was 130 kD. In conclusion, gallbladder bile contains nucleation promoting activity that binds to concanavalin A. The activity is increased in bile from patients with multiple cholesterol gallstones and could therefore play an important role in the pathogenesis of gallstone disease. PMID- 2328951 TI - Anesthesia and pressor responsiveness in chronic bile-duct-ligated dogs. AB - Cardiovascular homeostasis is comprised under general anesthesia and in jaundice. Because surgery is often performed on jaundiced patients, it is not altogether surprising that the incidence of perioperative complications is higher in such patients than in nonjaundiced ones. In this study we assessed the potential synergistic effects of anesthesia and jaundice on cardiovascular responsiveness of chronic bile-duct-ligated dogs. Responsiveness to norepinephrine, angiotensin II and isoproterenol was determined before and after chronic bile-duct ligation or sham-operation while the dogs were conscious or under halothane, fentanyl or pentobarbital-sodium anesthesia. These data have shown that halothane- and barbiturate-induced anesthesia do not alter mean arterial blood pressure in unoperated dogs when compared with conscious dogs before laparotomy. Furthermore, these two agents did not modify the pressor, dilator and positive inotropic responses to intravenous infusions of norepinephrine, angiotensin II and isoproterenol. Fentanol, however, reduced mean arterial blood pressure and heart rate without influencing responsiveness to the three vasoactive agents. Blunted responsiveness in the chronic bile-duct-ligated dogs to the three vasoactive agents was observed without any marked changes in mean arterial blood pressure or heart rate. The same blunted responses observed in the conscious, chronic bile duct-ligated dogs were also seen in the anesthetized, chronic bile-duct-ligated dogs. Halothane caused a marked hypotensive effect in the chronic bile-duct ligated dogs that was not seen in the sham-operated dogs. Conscious and anesthetized sham-operated dogs responded in the same manner as the conscious and anesthetized dogs before ligation. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328952 TI - Estrogen induction of hepatocellular carcinomas in Armenian hamsters. AB - Liver tumors were found in most Armenian hamsters (Cricetulus migratorius) injected with on 15-mg pellet of diethylstilbestrol. The tumors were detectable as early as 1 1/2 mo after diethylstilbestrol administration and were usually present as multiple nodules that progressively increased in size. Histologically, the multicentric neoplasms were all hepatocellular carcinomas of varied degrees of differentiation and frequently (42.8%) contained Mallory bodies; preneoplastic lesions were not observed. This hepatocellular carcinoma hamster model is unique because estrogen alone without any other known mutagen is responsible for induction of hepatocellular carcinoma. PMID- 2328953 TI - Response of fibronectin to liver regeneration after hepatectomy. AB - The relationship between plasma fibronectin concentration and the regenerative process in liver remnants after hepatectomy was studied in 12 patients and in male Sprague-Dawley rats with and without cirrhosis. Plasma fibronectin levels were reduced immediately after hepatectomy in humans and rats. Patients and rats without cirrhosis displayed preoperative fibronectin levels within 1 mo and 1 wk, respectively, but low fibronectin levels persisted longer in those with cirrhosis. Plasma fibronectin levels correlated well with the degree of hepatic regeneration in the patients with cirrhosis (r = 0.4227; p less than 0.05) and without cirrhosis (r = 0.8148; p less than 0.001), and also with the percentage of change in liver weight during regeneration in the rat with thioacetamide induced cirrhosis (r = 0.4905; p less than 0.01) or in the rat without cirrhosis (r = 0.6422; p less than 0.001). These results suggest that plasma fibronectin is a useful marker for the detection of regenerating liver. PMID- 2328954 TI - Stimulation of hepatic lipocyte collagen production by Kupffer cell-derived transforming growth factor beta: implication for a pathogenetic role in alcoholic liver fibrogenesis. AB - Transforming growth factor beta has a specific stimulatory effect on collagen formation by hepatic lipocytes, a cell type believed to be a major source of extracellular matrices in the liver. Because monocytes and macrophages are the known sources of transforming growth factor beta, Kupffer cells--resident macrophages in the liver--may also play an important role in liver fibrogenesis by releasing this cytokine and stimulating lipocyte collagen production. The present study tested this hypothesis using Kupffer cells and hepatic lipocytes isolated from a rat model of alcoholic liver fibrosis. Kupffer-cell-conditioned medium derived from the rat liver with alcoholic fibrosis, but not that from pair fed control animals, significantly stimulated the net collagen formation of lipocytes isolated from the alcohol-fed, pair-fed control and chow-fed animals. Acidification of the Kupffer-cell-conditioned medium potentiated this effect threefold to fourfold, indicating the presence of a latent form. Fractionation of the Kupffer-cell-conditioned medium by high-performance liquid chromatography gel filtration revealed the major peak of the stimulatory activity corresponding to the molecular weight between 20 kD and 30 kD. It was completely inhibited by anti transforming growth factor beta IgG. Furthermore, Northern blotting and hybridization of Kupffer-cell messenger RNA from alcohol-fed rats with 32P labeled transforming growth factor beta complementary DNA demonstrated the presence of 2.5 kb messenger RNA for this cytokine. We conclude that: (a) Kupffer cells isolated from the rat liver with alcoholic fibrosis express and release transforming growth factor beta; (b) that this cytokine is largely responsible for the Kupffer-cell-conditioned medium-induced stimulation of collagen formation by hepatic lipocytes; and (c) that this may represent a possible molecular mechanism of lipocyte stimulation during alcoholic liver fibrogenesis. PMID- 2328955 TI - Autoantibodies to isolated human hepatocyte plasma membranes in chronic active hepatitis. II. Specificity of antibodies. AB - The fine specificity of autoantibodies to human hepatocyte plasma membranes in autoimmune chronic active hepatitis was determined by one-dimensional immunoblotting. Sera from 12 patients with "classical" autoimmune chronic active hepatitis contained autoantibodies recognizing many human hepatocyte plasma membrane polypeptides in the 15 to 220 kD range. Many of these autoantibodies titrated beyond 1:80,000 and some may be potentially "pathological." In particular, one band with an apparent molecular weight of 60 kD was a dominant and consistent finding in all patients with autoimmune chronic active hepatitis by immunoblotting. Serum absorption studies showed this band to be predominantly liver-specific. Control sera from patients with chronic persistent hepatitis, nonhepatic autoimmune disease and normal healthy subjects possessed low titer reactivity that most likely represented "natural" autoantibodies. Anti-human hepatocyte plasma membranes in autoimmune chronic active hepatitis consisted of all three immunoglobulin isotypes (G,M and A) and their presence was not caused by nonspecific reactions as a consequence of hypergammaglobulinemia. Autoantibodies were shown to be specific by virtue of their absorption and exhaustion on titration. Many were directed at species nonspecific determinants, however, some autoantibodies recognized human-specific polypeptides. The majority of anti-human hepatocyte plasma membranes appeared to be organ-specific as sera from patients with autoimmune chronic active hepatitis reacted only weakly with polypeptides of kidney plasma membranes. Of the activity detected, few bands corresponded with those obtained using polypeptides of human hepatocyte plasma membranes. Our results show that patients with autoimmune chronic active hepatitis possess an array of liver-specific autoantibodies to polypeptide subunits of human hepatocyte plasma membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328956 TI - Immunopathology of acute galactosamine hepatitis in rats. AB - Galactosamine hydrochloride induces liver disease in rats that morphologically resembles drug-induced hepatitis in man. In this study we analyzed the character of the inflammatory reaction following the toxic damage resulting from the administration of galactosamine hydrochloride using a broad panel of monoclonal antibodies to lymphocyte subsets and macrophages. Fat-storing cells were identified with a polyclonal anti-desmin antibody. Cellular proliferation was assessed by labeling S-phase cells with the thymidine analog bromodeoxyuridine. Injection of galactosamine hydrochloride was associated with conspicuous hepatocyte necrosis and parenchymal granulocyte influx in the first 24 hr. Thereafter, mononuclear inflammatory cells predominated, mainly T lymphocytes and macrophages, with maximal numbers at 48 hr. The majority of T lymphocytes were CD8-positive cells and were located in the portal tracts and parenchyma. CD4 positive T cells were scarce and confined to the portal tracts. Proliferation of fat-storing cells paralleled hepatocyte regeneration with maximal values after 48 to 72 hr. The temporal relationship between infiltrating mononuclear cells, mainly T lymphocytes of CD8 phenotype and macrophages, fat-storing cell proliferation and hepatic regeneration suggests pathophysiological interactions between these cell types in liver injury in the rat after galactosamine hydrochloride administration. PMID- 2328957 TI - Cocaine-induced liver cell injury: comparison of morphological features in man and in experimental models. AB - Although investigative research of animal models in cocaine metabolism and associated liver cell injury has been fairly extensive during the past 10 yr, little evidence of hepatotoxicity has been documented in man. We report a case of fulminant hepatic failure and acute rhabdomyolysis resulting from cocaine use. Coagulative-type perivenular and midzonal necrosis and periportal microvesicular fatty change were the predominant morphological features throughout all lobules of the liver, in contrast to periportal necrosis described in the only previous case report with biopsy. Differences in zonal necrosis caused by the same drug are not typically seen in man experiencing direct or indirect intrinsic hepatotoxicity. However, experimental models have shown cocaine to have this ability, dependent on enzyme induction or inhibition, sex and dose. Therapeutic approaches for prevention of possible liver cell injury by cocaine toxicity are discussed. PMID- 2328958 TI - Hemodynamic effects of glucagon in portal hypertension. AB - It has been suggested that glucagon contributes to the pathogenesis of portal hypertension by increasing portal blood flow. This study examined this issue by assessing the hemodynamic effects of a pharmacological dose of glucagon (1 mg, intravenously) in patients with cirrhosis and portal hypertension (n = 10) and in subjects without significant liver disease (controls = n = 5). Patients with cirrhosis had much higher glucagon levels than control subjects (875 +/- 167 vs. 186 +/- 25 pg/ml, p less than 0.01) and showed blunted hemodynamic responses after glucagon administration. This occurred despite greater circulating glucagon levels, probably because of a significant prolongation of the plasma half-life of exogenously administered glucagon (4.9 +/- 0.4 vs. 2.7 +/- 0.1 min, p less than 0.1). Control subjects had marked increases in heart rate (+ 19% +/- 4%, p less than 0.01), cardiac index (+ 16% +/- 4%, p = 0.01) and arterial pressure (+ 10% +/- 3%, p less than 0.05), but corresponding changes in patients with cirrhosis (+ 7% +/- 1%, + 6% +/- 1%, and + 6% +/- 2%, respectively) were significantly less pronounced (p = 0.05), and there was a negative correlation between basal glucagon levels and the response of heart rate to glucagon injection (r = -0.804, p less than 0.001). Resistance to the systemic effects of glucagon in cirrhosis may thus be caused by a down-regulation of vascular glucagon receptors. In addition, glucagon administration caused a significant increase in portal pressure (from 18.1 +/- 1.1 to 19.0 +/- 1.2 mm Hg, p less than 0.01), as well as in azygos blood flow (from 0.54 +/- 0.03 to 0.64 +/- 0.04 L/min, + 19% +/- 4%, p less than 0.02), reflecting increased portocollateral blood flow. These findings are consistent with the hypothesis that glucagon is one of the factors contributing to the splanchnic vasodilatation and increased portal pressure of cirrhosis. PMID- 2328959 TI - The effects of ethanol administration on portal pressure and gastroesophageal collateral blood flow in patients with alcoholic cirrhosis. AB - The pathogenesis of variceal hemorrhage is not well understood. Portal pressure and gastroesophageal collateral (azygous) blood flow are similar in patients with cirrhosis with or without a history of variceal bleeding. However, acute increases in these parameters in individual patients might predispose them to variceal rupture. Fifteen patients with alcoholic cirrhosis and portal hypertension were evaluated to test the hypothesis that ethanol intake acutely increases portal pressure or gastroesophageal blood flow and is a possible risk factor in variceal hemorrhage. A 10% solution of ethanol in 5% dextrose in water was infused intravenously at a rate sufficient to raise the blood-alcohol level to 100 mg/dl over 30 min. Eight patients received ethanol 5% dextrose in water; seven patients received a placebo (5% dextrose in water alone). Ethanol did not produce a significant change in wedged hepatic-vein pressure, free hepatic-vein pressure, azygous blood flow, mean arterial pressure or heart rate compared with the effects of 5% dextrose in water alone. Acute administration of ethanol does not increase portal pressure or gastroesophageal blood flow. It is unlikely that acute ethanol ingestion is a risk factor for variceal hemorrhage. PMID- 2328960 TI - Methanethiol metabolism and its role in the pathogenesis of hepatic encephalopathy in rats and dogs. AB - The metabolism of methanethiol was studied in rats. Administration of a noncomatogenic dose of methanethiol through inspired air or injection into the upper colon resulted in an elevation of the concentrations of methanethiol mixed disulfides in serum (protein--S--S--CH3 and X--S--S--CH3, X yet unknown) and in urine (X--S--S--CH3). The concentrations of methanethiol mixed disulfides proved to be a relative measure of exposure to methanethiol. The levels of volatile sulfur compounds methanethiol, dimethylsulfide and dimethyldisulfide in the air expired by rats exposed to a noncomatogenic dose of methanethiol through the colon were also elevated. Rats with acute hepatic encephalopathy caused by liver ischemia also showed elevation of methanethiol mixed disulfide levels on challenge of methanethiol through the colon or inspired air, but to a significantly smaller extent than did the corresponding sham-operated rats. This suggests that the liver is at least partly responsible for formation of methanethiol mixed disulfides. No additional toxic effects were observed in the rats with ischemic livers on methanethiol exposition when compared with normal rats, suggesting that the liver does not play an essential role in methanethiol detoxification. Metabolism of methanethiol by blood to sulfate, for example, might be more important. In rats with acute hepatic encephalopathy caused by liver ischemia and in dogs suffering from hepatic encephalopathy resulting from chronic liver disease, large and significant increases in ammonia levels were measured. However, the mean levels of methanethiol mixed disulfides in rats and dogs with hepatic encephalopathy were not different from the mean normal levels in these animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2328961 TI - Inhibition of HBV replication during coinfection with HBV and HDV: inhibition of the inhibition by coinfection with HIV. PMID- 2328962 TI - MHC antigen expression in human liver grafts: its role in rejection. PMID- 2328963 TI - Intracellular acidosis: can it delay the inevitable? PMID- 2328964 TI - Chin marking behavior, sexual receptivity, and pheromone emission in steroid treated, ovariectomized rabbits. AB - The effect of daily injections of estradiol benzoate (1 or 10 micrograms) and of progesterone (10 mg) on chin marking activity, sexual receptivity, and emission of nipple-search pheromone in ovariectomized rabbits was investigated. Both estradiol treatments resulted in a significant increase in all three measures over baseline and control group levels within 1-3 days, and withdrawal in a return to pretreatment levels within 2 weeks (Experiment I). In contrast, the administration of progesterone to such estradiol-primed does resulted in an almost immediate suppression of chin marking and lordosis, but in marked enhancement of pheromone emission and aggressive behavior (Experiment II). However, progesterone given alone to nonprimed does had no effect on any of these measure (Experiment III). The response profiles resulting from these treatments correspond well to patterns reported for intact does during estrus (= estradiol alone), pregnancy (= estradiol plus progesterone), and at parturition (= progesterone withdrawal). PMID- 2328965 TI - Plasma prolactin concentrations in breeding pied flycatchers (Ficedula hypoleuca) with an experimentally prolonged brooding period. AB - This experiment explored the stimulatory effect of brooding newly hatched young on plasma prolactin concentration in male and female pied flycatchers, Ficedula hypoleuca. By exchanging offspring between nestboxes, one group of parents was exposed to 1- to 3-day-old nestlings for 12 days. Females in this group continued night-time brooding during these 12 days. The females, but not the males (who do not participate in brooding nestlings), after 6 days had higher plasma prolactin concentrations than control birds which had shown a 50% reduction in night-time brooding at this stage. By Day 12, however, prolactin concentration had decreased to the same level as in control birds, even though these females were still brooding 3-day-old nestlings. Female flycatchers given 3-day-old nestlings on the day their own eggs hatched showed an earlier reduction in night-time brooding and an earlier decrease in plasma prolactin than did control birds. An early decrease in prolactin was also seen in the males of this experimental group. PMID- 2328966 TI - Sexual differentiation of behavior in the zebra finch: effect of early gonadectomy or androgen treatment. AB - Treatment of nestling zebra finches with estradiol benzoate (EB) has been shown to masculinize singing in females and demasculinize copulatory behavior in males, suggesting that sexual differentiation of these behaviors is under hormonal control such that testicular hormones induce the capacity for song and ovarian hormones suppress the capacity for mounting. Two experiments were carried out to obtain a more complete picture of sexual differentiation in this species. In Experiment 1, nestlings were injected daily for the first 2 weeks after hatching with testosterone propionate (TP), dihydrotestosterone propionate (DHTP), or a combination of DHTP and EB. As adults, birds were gonadectomized and implanted with TP prior to testing, then tested again after implantation with EB. Singing was not increased in females by any of the treatments. The only effect of either TP or DHTP given alone was defeminization of female proceptive behavior by DHTP. Thus androgens appear to have less influence than estrogens on sexual differentiation of behavior in this species. The combination of DHTP and EB demasculinized mounting in males. In Experiment 2, nestlings were gonadectomized at 7-9 days of age and implanted with TP prior to testing in adulthood. Early gonadectomy had little effect on later behavior; early castrated males sang, danced, and copulated normally and early ovariectomized females neither sang nor mounted. PMID- 2328967 TI - Blockade of lordosis by androst-1,4,6-triene-3,17-dione (ATD) and tamoxifen in female hamsters primed with testosterone propionate. AB - Normal female hamsters display lordosis after testosterone propionate (TP) plus progesterone (P) treatments. Such effect is probably mediated through aromatization of testosterone (T) into estradiol. If so, then an aromatase inhibitor (ATD) or an estrogen antagonist (tamoxifen, TAM) should be able to block the activational effect of T on lordosis. To test this hypothesis, 48 ovariectomized female hamsters were assigned into six groups which, according to treatments received, were ATD + TP, TAM + TP, OIL + TP, ATD + EB (estradiol benzoate), TAM + EB, and OIL + EB groups. The groups received assigned treatments for 2 days and were injected with P on the third day. Five minutes of behavior test was conducted 4 hr after P injection. The OIL + TP, OIL + EB, and ATD + EB groups all had averaged total lordosis duration (TLD) longer than 200 sec. The TLD of the TAM + EB group was only 117 sec. The ATD + TP and TAM + TP groups showed almost no lordosis. The results showed that the estrogen antagonist (TAM) impaired lordosis no matter whether the animals were primed with TP or EB, but the aromatase inhibitor (ATD) blocked lordosis only in TP primed females. It is concluded that the aromatization of T to estrogen is required for testosterone activation of lordosis in female hamsters. PMID- 2328968 TI - Evidence for "memory" of cervical stimulation for the promotion of pregnancy in rats. AB - Successful pregnancy in the female rat depends upon two sets of physiological events: (1) transport of gametes (sperm and egg) through the reproductive tract so that fertilization can be effected and (2) establishment of an appropriate hormonal environment (progestational state) so that the fertilized egg can implant in the uterus and be maintained during subsequent gestation. This study highlights the independence of the mechanisms controlling the gametic and hormonal aspects of pregnancy by temporally separating the introduction of sperm into the female from the stimulation that triggers the progestational hormonal response. The progestational state was initiated by electrical stimulation of the cervix, and sperm was introduced directly into the uterus by artificial insemination. Although these two events were separated by up to 3 days, pregnancy could ensue. Cervical stimulation, normally a consequence of male intromission behavior, establishes a condition in the central nervous system, a "memory" that signals the probable induction of pregnancy. Without this "memory," animals with a short estrous cycle would continue to cycle after mating, thereby producing a hormonal environment incompatible with implantation. The "memory" is manifested by daily surges of prolactin irrespective of fertilization. This is the first physiological demonstration that a "memory" of cervical stimulation can be called upon to support a viable pregnancy. PMID- 2328969 TI - Lordosis behavior in intact male rats: effects of hormonal treatment and/or manipulation of the olfactory system. AB - The aim of this study was to investigate the olfactory mechanisms regulating the display of lordosis behavior in intact Wistar male rats bred in our colony. Gonadally intact males show a low capacity to respond by lordosis to male mounts and were insensitive to manipulations of the olfactory system (exposure to the odor of male urine or accessory bulb removal (AOBR)) which have been previously shown to facilitate the display of lordosis behavior in orchidectomized animals primed with ovarian hormones. Treatment with either estradiol benzoate (EB) or EB and progesterone (P) consecutively did not render these gonadally intact animals sensitive to the effects of AOBR. By contrast exposure to male urine was capable of facilitating the display of lordosis behavior in intact male rats given EB + P consecutively. These results are discussed in the light of previous findings showing that (1) two inhibitory structures, the accessory olfactory bulb and the septal and preoptic areas, are involved in the control of lordosis behavior in the male rat; (2) the effects of olfactory cues on the display of lordosis behavior are dependent on the action of both EB and P in orchidectomized animals. PMID- 2328970 TI - Unexpected changes in urinary catecholamines and vanillylmandelic acid following rape assault. AB - Although psychological changes are recognized to occur in rape assault survivors there is no information on the biochemical changes in these victims. This study compares urinary catecholamines and metabolites in 17 rape victims to two female control groups (one of which engaged in normal sexual intercourse and the other did not). We found, in the rape victims, unexpected changes in the excretion pattern of catecholamines and metabolites as compared to the various control groups. The most significant difference was the dramatic increase in urinary conjugated dopamine (P less than 0.01) in the rape victims which remained elevated for over 24 hr. Urinary vanillylmandelic acid (VMA) rose significantly in rape assault victims when compared to the normal control group. The VMA levels in rape victims were significantly lower, however, than in the women who had undergone (normal) sexual intercourse (P less than 0.01). Urinary free epinephrine showed a marked decline and remained depressed for over 24 hr in the rape assault victims (P less than 0.01) compared to normal controls. Some possible reasons for these patterns in catecholamines and metabolite excretion are suggested. These changes may be of importance in the poststress syndrome that occurs following the rape assault. In summary, a different profile of catecholamine and metabolite excretion patterns was found in rape compared to normal sexual intercourse. The enhanced dopamine excretion is contrary to the expected change of enhanced epinephrine secretion in severe stress. PMID- 2328971 TI - Estradiol administration and the sexual activity of castrated male rhesus monkeys (Macaca mulatta). AB - To examine whether estradiol might be effective in maintaining sexual behavior after castration or after testosterone withdrawal, we have observed male rhesus monkeys during daily 1-hr tests alternately with each of two ovariectomized, estradiol-treated females (four males, four females, eight male-female pairs, 798 tests). Estradiol (2-5 micrograms/kg sc/day) or vehicle was administered in counterbalanced order immediately after castration and again immediately after withdrawal of testosterone propionate treatments (800 micrograms and 1.6 mg sc/day). There were no significant differences in behavior during vehicle and estradiol treatments to indicate that estradiol helped to maintain male sexual activity. Instead, estradiol treatment tended to interfere with the capacity to intromit. This supported the results of other studies, namely, that the systemic administration of estradiol does not enhance the sexual behavior of castrated male macaques, and raises questions about the role of both aromatization and estrogen receptors in the male primate brain. PMID- 2328972 TI - Plasma levels of prolactin and gonadal steroids in relation to multiple-brooding and renesting in free-living populations of the song sparrow, Melospiza melodia. AB - Plasma levels of testosterone (T), estradiol (E2), and prolactin were measured in samples collected from free-living song sparrows, Melospiza melodia. In males, plasma levels of T were elevated early in the season when territories were established and when females laid the first clutch of eggs. Thereafter, T levels declined and remained low throughout the remainder of the breeding cycle. However, if the first brood was lost to a predator, or by experimental removal of the nest, plasma levels of T increased as renesting, to replace the clutch, occurred. Circulating levels of prolactin in males began to rise during the egg laying stage of the first brood, reached a maximum toward the end of the incubation stage, remained elevated until breeding was terminated, and then declined throughout the moulting stage to basal values in October. Prolactin levels remained high throughout the breeding season irrespective of whether a brood was raised successfully or whether the nest was lost and renesting occurred. In females, plasma levels of E2 were elevated prior to the egg-laying stage for each brood as is typical of multiple-brooded species. However, prolactin titers rose dramatically during egg-laying for the first clutch (slightly higher than in males) and were maximal by onset of incubation. Only females of this species incubate, although males do feed young. As in males, plasma prolactin in females remained high between broods and during experimentally induced renesting, and then declined to basal by the end of the moult stage in October. These data suggest that there are no differences in the temporal patterns of prolactin concentrations in blood between multiple-brooding and renesting. In a separate experiment, captive male song sparrows were transferred from a short day to artificial long days (18L 6D) and a control group was maintained on 9L 15D. In the long-day group, prolactin levels rose abruptly over the first 20 days, as the testes developed, and remained high well into postnuptial moult after the gonads had regressed. Prolactin remained basal in the control group. These data suggest that the temporal pattern of circulating prolactin levels throughout the breeding season is regulated at least partly by changing photoperiod. However, nonphotoperiodic factors are also important since photoperiodically induced increases in prolactin are significantly less than those seen in free-living individuals. These differences may be related to parental behavior. PMID- 2328973 TI - Hospital CEOs pinpoint top priority programs. PMID- 2328974 TI - On the front lines of policymaking. AB - We generally associate policies with specific issues. But policies are made by people--frequently by politicians. And the policymaking process is often best explored through the stresses and strains that the process exerts on policymakers. To illustrate more clearly the thinking processes of policymakers and the choices they must make daily, Hospitals' contributing editor Emily Friedman followed a respected health policy leader through a typical day. PMID- 2328975 TI - AHA: utilization declines; financial pressures moderate. AB - Data for the fourth quarter of 1989 did not hold any surprises. Performance indicators for community hospitals continue to follow the paths established in previous quarters. According to data from the American Hospital Association, utilization declined, hiring increased, and financial pressures eased slightly. PMID- 2328976 TI - JCAHO gets lukewarm reviews from its CEO opinion survey. AB - CEOs from 923 hospitals gave the JCAHO mixed reviews in a recent survey: 38 percent thought JCAHO's performance had improved over the past five years; 26 percent thought it had worsened; and 27 percent saw no change. Depending upon who you talk to, the results are either good or bad. PMID- 2328977 TI - CEO walkabouts get firsthand look at employee problems. AB - "The CEO doesn't take care of patients; the CEO takes care of the people who take care of patients," says Eire "Chip" Chapman, the president of 869-bed Riverside Methodist Hospitals. This philosophy is endorsed by other top administrators who have made a point to leave their desks to investigate first-hand employee concerns and work situations. PMID- 2328978 TI - Hospitals slowly but surely join the video era. PMID- 2328979 TI - CEOs skeptical of Bush's health policy stance. PMID- 2328980 TI - Social worker: we 'do good' for the hospital's bottom line. PMID- 2328981 TI - Hispanic health issues are #1 at border hospital. PMID- 2328982 TI - AMS software helps hospitals manage expenses. PMID- 2328983 TI - CEO burnout: shift priorities to manage stress. PMID- 2328984 TI - Who will decide the future of health care? PMID- 2328985 TI - Compassion, payment, and leadership. PMID- 2328986 TI - A primary map of 24 loci on human chromosome 16. AB - A primary genetic map of chromosome 16 has been constructed by linkage analysis of 24 polymorphic loci, typed in 59 reference families. These loci form a continuous map that covers the whole chromosome and spans genetic distances of 187 cM in males and 226 cM in females. Most of the sex-specific recombination rate difference comes from a nontelomeric region that covers 10 cM in males and 74 cM in females. Both telomeric regions show the opposite trend, with a significant increase in the male recombination rate. PMID- 2328987 TI - The gene for the beta-subunit of retinal transducin (Gnb-1) maps to distal mouse chromosome 4, and related sequences map to mouse chromosomes 5 and 8. AB - The heterotrimeric G protein transducin releases cGMP-phosphodiesterase from inhibition in retinal rod photoreceptor cells when stimulated by light-activated rhodopsin. As a result the level of cGMP goes down, the rod plasma membrane hyperpolarizes, and the release of neurotransmitter is modified. We have used a bovine cDNA for the beta-subunit of transducin (G beta 1) to map its gene Gnb-1 to distal mouse chromosome 4. This cDNA also identified two other homologous sequences in the mouse genome. One of the sequences was on chromosome 5 which we identified as the locus of Gnb-2, a second G protein beta-subunit gene. The other sequence was on chromosome 8 and is either a pseudogene or an as yet undiscovered third G beta-subunit gene, here termed Gnb-3. PMID- 2328988 TI - Assignment of the gene for neuroendocrine protein 7B2 (SGNE1 locus) to mouse chromosome region 2[E3-F3] and to human chromosome region 15q11-q15. AB - The gene for 7B2, a protein found in the secretory granules of neural and endocrine cells (gene symbol SGNE1) was localized to the E3-F3 region of mouse chromosome 2 and to the q11-q15 region of human chromosome 15. This was determined by in situ hybridization, using a mouse 7B2 cDNA and an intronic fragment of the corresponding human gene as probes. The respective locations of SGNE1 in the two species correlate with the conservation of loci between these subregions of mouse chromosome 2 and human chromosome 15. Clinically, the human SGNE1 DNA fragment may serve as a molecular probe of this locus in both the Prader-Willi and the Angelman syndromes, which are often accompanied by submicroscopic chromosomal deletions in the 15q11-15q13 region. PMID- 2328989 TI - Assignment of 35 single-copy and 17 repetitive sequence DNA probes to human chromosome 3: high-resolution physical mapping of 7 DNA probes by in situ hybridization. AB - Thirty-five single-copy and 17 repetitive sequence DNA probes specific for human chromosome 3 were isolated from human chromosome 3-derived genomic libraries. Seven DNA clones, including three that are polymorphic for BglII or MspI, were mapped by in situ hybridization. Four probes were mapped to 3p subregions and 3 were mapped to 3q subregions. Three of the DNA sequences map to regions overlapping a segment of chromosome 3 (3p14-23) frequently deleted in small cell lung cancer cells. By Southern blot analysis on a deletion hybrid panel, we previously mapped 6 of these probes to three distinct chromosome 3 subregions. Our in situ data support these assignments and more precisely determine the localization of each clone to the following regions: D3S34 (3p14-21), D3S35 (3p21), D3S39 (3p21), D3S40 (3p12-13), D3S37 (3q21-23), and D3S36 (3q21). Clone pL84c, a low repeat sequence clone (approximately 30 copies), was mapped to the 3q21-29 subregion. These DNA clones mapped by in situ hybridization can provide useful landmarks for the ordering and localization of other clones. PMID- 2328990 TI - Rapid isolation of DNA probes within specific chromosome regions by interspersed repetitive sequence polymerase chain reaction. AB - A method was recently developed for the specific amplification of human DNA sequences from interspecific somatic cell hybrids by the polymerase chain reaction (PCR) using primers directed to Alu, a short interspersed repeat element (SINE). We now show human-specific amplification using a primer to the 3' end of the human long interspersed repeat element L1Hs (LINE). A monochromosomal hybrid containing an intact human X chromosome yielded approximately 25 discrete products, ranging in size from 800 to 4500 bp. Combination of a single Alu primer and the L1Hs primer yielded a large number of smaller products (300-1000 bp) distinct from those observed with either primer alone. Inspection of ethidium bromide-stained gels showed one Alu-Alu and three Alu-L1Hs products which were present in an intact X chromosome but absent in a hybrid containing an X chromosome deleted for the single metaphase band q28. These four fragments were isolated from the gel and used as probes on Southern blots which confirmed their localization to Xq28. These results demonstrate that primers can be constructed to a variety of interspersed repetitive sequences (IRS) and used individually or in combination for the rapid isolation of DNA fragments from defined chromosomal regions by IRS-PCR. PMID- 2328991 TI - Microdissection of the Prader-Willi syndrome chromosome region and identification of potential gene sequences. AB - The Prader-Willi syndrome chromosome region on the long arm of human chromosome 15 was microdissected and microcloned from 20 GTG-banded metaphase chromosomes, and 5000 recombinant clones were obtained. Of these clones, 39% identify single copy human DNA sequences, most of which map to the dissected chromosome region and are evolutionarily conserved in other species. Three of eleven clones studied in detail are deleted in several patients with Prader-Willi syndrome. The microclones will be useful for the physical characterization of the Prader-Willi syndrome chromosome region and the identification of the affected genes in this disease. PMID- 2328992 TI - Long-range physical mapping around the human steroid sulfatase locus. AB - The region of the human X chromosome containing the steroid sulfatase locus was analyzed by pulsed-field gel electrophoresis. Restriction site maps were generated for the X chromosome in the blood of a normal male individual and that in the mouse-human hybrid cell line ThyB-X; these maps extend over approximately 4.3 Mb of DNA of the former, and 3.2 Mb of the latter. Physical linkage was defined between the STS locus and sequences detected by the probes GMGX9 (DXS237), GMGXY19 (DYS74), CRI-S232 (DXS278), and dic56 (DXS143), and the order telomere--(STS, DYS74)--DXS237--DXS278--DXS143--centromere was deduced. The pulsed-field maps were used to demonstrate a deletion of 180 kb of DNA from the X chromosome of an individual with X-linked ichthyosis. Also, possible locations for the Kallmann syndrome gene were revealed, and the distance between the steroid sulfatase locus and the pseudoautosomal region was estimated to be at least 4 Mb. PMID- 2328993 TI - The gene for the RNA component of the mitochondrial RNA-processing endoribonuclease is located on human chromosome 9p and on mouse chromosome 4. AB - Mitochondrial RNA-processing endoribonuclease (RNAase MRP) has the capacity to cleave mitochondrial RNA complementary to the light strand of the displacement loop at a unique site. The enzyme is a ribonucleoprotein whose RNA component is a nuclear gene product. The 5' flanking region of the primary transcript has control elements characteristic of RNA polymerase II transcription, and the coding region has features of RNA polymerase III transcription signals. The RNA associated with RNAase MRP is the first known RNA encoded by a single-copy gene in the nucleus and believed to be imported into mitochondria. The gene (RMRP) for this RNA component of RNAase MRP was assigned to human chromosome 9 and mouse chromosome 4 by Southern blot analyses of 11 human X rodent hybrids and 11 mouse X rodent hybrids with probe pHM1.0 and probe pSP270, respectively. In situ hybridization of probe pHSTU300 to normal human chromosomes revealed 29 of 100 cells with label on 9p and 9.6% of 302 silver grains located at 9p21--p12. PMID- 2328994 TI - Confirmation of linkage in von Hippel-Lindau disease. AB - Von Hippel-Lindau (VHL) disease was initially reported to be linked to the RAF1 oncogene (3p25). We have ascertained and sampled two large multigenerational VHL families for linkage studies, in order to confirm the localization of the VHL gene as a prelude to fine mapping studies. The probes used in the analysis were p627 (RAF1) and pHeA12 (thyroid hormone receptor B) (3p24.1-3p22). VHL was analyzed as an autosomal dominant trait with age-dependent penetrance. The maximum lod score combining both families was z(theta) = 2.16 at theta = 0.0 for RAF1 and z(theta) = 2.20 at theta = 0.05 for thyroid hormone receptor B. Multipoint analysis using the RAF1 and thyroid hormone receptor B loci resulted in a peak lod score of 3.1 confirming linkage of VHL to this region of chromosome 3. However, the position of VHL relative to the two loci could not be established with certainty. PMID- 2328995 TI - Linkage relationships of the Wiskott-Aldrich syndrome to 10 loci in the pericentromeric region of the human X chromosome. AB - Twelve families with Wiskott-Aldrich syndrome (WAS) were studied by linkage analysis using 10 polymorphic marker loci from the X-chromosome pericentromeric region. The results confirm close linkage of WAS to the DXS14, DXS7, TIMP, and DXZ1 loci and are consistent with previous data suggesting that WAS maps to the proximal Xp and is flanked by the DXS14 and DXS7 loci. The strongest linkage (Z = 10.19 at theta = 0.00) was found to be between WAS and the hypervariable DXS255 locus, a marker locus already mapped between DXS7 and DXS14 and which was informative for all meioses included in this analysis. Linkage of the WAS to two pericentromeric Xq loci, DXS1 and PGK1, was also established. On the basis of these results, accurate predictive testing should now be feasible in the majority of WAS families. PMID- 2328997 TI - The application of neural networks to myoelectric signal analysis: a preliminary study. AB - Two neural network implementations are applied to myoelectric signal (MES) analysis tasks. The motivation behind this research is to explore more reliable methods of deriving control for multidegree of freedom arm prostheses. A discrete Hopfield network is used to calculate the time series parameters for a moving average MES model. It is demonstrated that the Hopfield network is capable of generating the same time series parameters as those produced by the conventional sequential least squares (SLS) algorithm. Furthermore, it can be extended to applications utilizing larger amounts of data, and possibly to higher order time series models, without significant degradation in computational efficiency. The second neural network implementation involves using a two-layer perceptron for classifying a single site MES based on two features, specifically the first time series parameter, and the signal power. Using these features, the perceptron is trained to distinguish between four separate arm functions. The two-dimensional decision boundaries used by the perceptron classifier are delineated. It is also demonstrated that the perceptron is able to rapidly compensate for variations when new data are incorporated into the training set. This adaptive quality suggests that perceptrons may provide a useful tool for future MES analysis. PMID- 2328996 TI - Ampd-2 maps to distal mouse chromosome 3 in linkage with Ampd-1. PMID- 2328998 TI - Stability in contractive nonlinear neural networks. AB - We consider models of the form mu chi = -x + p + WF(x) where x = x(t) is a vector whose entries represent the electrical activities in the units of a neural network. W is a matrix of synaptic weights, F is a nonlinear function, and p is a vector (constant or slowly varying over time) of inputs to the units. If the map WF(x) is a contraction, then the system has a unique equilibrium which is globally asymptotically stable; consequently the network acts as a stable encoder in that its steady-state response to an input is independent of the initial state of the network. We consider some relatively mild restrictions on W and F(x), involving the eigenvalues of W and the derivative of F, that are sufficient to ensure that WF(x) is a contraction. We show that in the linear case with spatially-homogeneous synaptic weight, the eigenvalues of W are simply related to the Fourier transform of the connection pattern. This relation makes it possible, given cortical activity patterns as measured by autoradiographic labeling, to construct a pattern of synaptic weights which produces steady state patterns showing similar frequency characteristics. Finally, we consider the relationships, in the spatial and frequency domains, between the equilibrium of the model and that of the linear approximation mu chi = -x + p + Wx; this latter equilibrium can be computed easily from p in the homogeneous case using discrete Fourier transforms. PMID- 2328999 TI - The dynamic response model of nine different skeletal muscles. AB - The frequency response model of nine different skeletal muscles in the hindlimb of the cat was determined with the aide of electrical nerve stimulation which allows orderly stimulation of motor units concurrently with firing rate increase. It was shown that the general model consists of a linear second-order system with double real poles and a pure time delay. The pole values were different for the different muscles, ranging from 1.55 to 2.8 Hz. Similarly, the pure time delay varied from muscle to muscle, ranging from 8 to 17 ms. Statistical analysis demonstrates that under isometric contraction with force oscillations in the range of 10-90% of maximal the model poles are determined, and could be predicted, from the muscles functional and anatomical location in the limb and from its pennation pattern. PMID- 2329000 TI - Potential distribution in three-dimensional periodic myocardium--Part I: Solution with two-scale asymptotic analysis. AB - The use of two-scale asymptotic analysis allows development of a model of the steady-state potential distribution in three-dimensional cardiac muscle preserving the underlying cellular network. The myocardium is modeled as a periodic structure consisting of cylindrical cells embedded in extracellular fluid and connected by longitudinal and side junctions. The method is applicable to cardiac muscle of arbitrary extent since the periodicity of the tissue is dealt with analytically, and thus numerical computations require no more resources than a continuous volume conductor problem. The asymptotic analysis approach reveals that the potential in a periodic myocardium consists of two components. The large-scale component provides the baseline for the total solution and can be determined from the anisotropic monodomain model associated with the original periodic problem. The method provides the formula for calculating the conductivity of the equivalent monodomain model on the basis of cell geometry and conductivity distribution in the cardiac tissue. The small scale component reflects the periodicity of the underlying structure and oscillates with periods determined by the dimensions of cardiac cells. The magnitude of these oscillations depends upon the gradient of the large-scale component. During stimulation with extracellular electrodes, the small-scale component determines both the shape and the magnitude of the transmembrane potential, while the influence of the large-scale component is negligible. Hence, the small-scale component merits closer attention in pacing and defibrillation studies, especially since the model based on two-scale asymptotic analysis provides an effective means of its computation. PMID- 2329001 TI - Potential distribution in three-dimensional periodic myocardium--Part II: Application to extracellular stimulation. AB - Modeling potential distribution in the myocardium treated as a periodic structure implies that activation from high-current stimulation with extracellular electrodes is caused by the spatially oscillating components of the transmembrane potential. This hypothesis is tested by comparing the results of the model with experimental data. The conductivity, fiber orientation, the extent of the region, the location of the pacing site, and the stimulus strength determined from experiments are components of the model used to predict the distributions of potential, potential gradient, and the transmembrane potential throughout the region. Next, assuming that a specific value of the transmembrane potential is necessary and sufficient to activate fully repolarized myocardium, the model provides an analytical relation between large-scale field parameters, such as gradient and current density, and small-scale parameters, such as transmembrane potential. This relation is used to express the stimulation threshold in terms of gradient or current density components and to explain its dependence upon fiber orientation. The concept of stimulation threshold is generalized to three dimensions, and an excitability surface is constructed, which for cardiac muscle is approximately conical in shape. The numerical values of transmembrane potential and stimulation thresholds calculated using asymptotic analysis are in agreement with the results of animal experiments, confirming the validity of this approach to study the electrophysiology of periodic cardiac muscle. PMID- 2329002 TI - Multichannel adaptive enhancement of the electrogastrogram. AB - The electrogastric signal can be measured cutaneously on the abdomen. This is attractive because it is harmless to patients or volunteers. However, the poor quality of the cutaneous measurements necessitates signal enhancements. Hence, in this paper, an adaptive multichannel signal enhancing system is proposed. The mu vector least mean square (LMS) algorithm is applied to adjust the weights of the adaptive filters in the system. The detailed description and the performance analysis of the system is given in the paper. Applying the proposed system, the respiratory artifact, the electrode-skin noise, some of motion artifacts, and the electrocardiography (ECG) can be efficiently reduced while the characteristics of the relevant gastric signal is less affected. PMID- 2329003 TI - Medical imaging with a microwave tomographic scanner. AB - A microwave tomographic scanner for biomedical applications is presented. The scanner consists of a 64 element circular array with a useful diameter of 20 cm. Electronically scanning the transmitting and receiving antennas allows multiview measurements with no mechanical movement. Imaging parameters are appropriate for medical use: a spatial resolution of 7 mm and a contrast resolution of 1% for a measurement time of 3 s. Measurements on tissue-simulating phantoms and volunteers, together with numerical simulations, are presented to assess the system for absolute imaging of tissue distribution and for differential imaging of physiological, pathological, and induced changes in tissues. PMID- 2329004 TI - Frequency analysis of the peripheral pulse wave detected in the finger with a photoplethysmograph. AB - A photoelectric plethysmograph is described that performs a frequency analysis of the peripheral volume pulse wave using a portable computer. It was used to determine how the pulse shape varied with age using 54 subjects in three age groups, 10-29, 30-59, and 60-89 years. The youngest group had a larger power in the second harmonic, (normalized to the fundamental), with p less than 0.05 than the older two groups. The decrease of power in the harmonics of the peripheral pulse wave with age may be a useful noninvasive measure of aging and vascular disease. PMID- 2329005 TI - The influence of stimulation pulse frequency on the generation of joint moments in the upper limb. AB - Six muscles of the upper limb were stimulated transcutaneously. This communication reports the influence of the stimulation pulse frequency on the isometric joint moment generated by each muscle. A lower frequency of stimulation, the critical fusion frequency, was found for each muscle at which contractions ceased to be tetanic. This fusion frequency was correlated with muscle function. The magnitude of the joint moment was examined as a function of the stimulation pulse frequency for the six muscles tested. Parabolic curves were found to best fit this relationship; the magnitude of the moment reaching a maximum at typically 50 Hz, and often decreasing at higher frequencies. The slope of the linear portion of the relationship between the generated joint moment and the stimulation current intensity was shown to be a function of the stimulation pulse frequency. This function was found to be similar to the form of the joint moment versus pulse frequency curve. Fatigue curves were plotted at different stimulation frequencies; demonstrating reduced fatigue at lower stimulation frequencies. A model was presented of the fatigue curve as an exponential function of time. We conclude that a stimulation frequency of 15 Hz is optimal for the upper limb muscles with a working range of 15-50 Hz where stimulation frequency is one of the parameters used to modulate the muscle contraction force. PMID- 2329006 TI - Nomenclature for the major histocompatibility complexes of different species: a proposal. PMID- 2329009 TI - Peptic ulcer disease. PMID- 2329008 TI - The rat MHC and cystathionine beta-synthase gene are syntenic on chromosome 20. PMID- 2329007 TI - Polymorphisms and diversity of T-cell receptor-gamma proteins expressed in mouse spleen. AB - Bulk populations of T-cell receptor (Tcr) gamma delta-expressing splenocytes from different inbred strains of mice were examined for the diversity of Tcr gamma delta proteins. Immunoprecipitations with anti-C gamma 1/2, anti-C gamma 4, and anti-V gamma 1 sera demonstrated that splenocytes from B10.BR, C57BL/6, and C57L strains of mice expressed the same array of Tcr gamma proteins, namely V gamma 1 C gamma 2, V gamma 1-C gamma 4, and V gamma 2-C gamma 1, although the Tcr gamma delta heterodimers observed for each of these strains were biochemically distinct. Examination of bulk splenic Tcr gamma delta heterodimers from several other inbred strains of mice demonstrated that each of the strains could be categorized into one of three basic phenotypes. For several reasons, the differences observed between the strains appeared to be solely dependent on polymorphisms of the Tcrg loci. First, F1 mice co-expressed both parental Tcr gamma delta phenotypes. Second, the distinguishing polymorphism between mice of phenotype 1 and phenotypes 2 or 3 was due to the presence of an N-linked glycosylation site within the Tcrg-Cl gene segment, previously described for BALB.B and C57BL/6 Tcrg-Cl genes. Finally, the V gamma 1-C gamma 4 polymorphism between mice of phenotype 3 and phenotypes 1 or 2 was due to differences in core protein size. Furthermore, the three defined Tcr gamma chains were expressed independently of the major histocompatibility complex (MHC) haplotype. Although no striking qualitative differences in Tcr gamma delta heterodimers were observed between strains (including those with autoimmune disorders), a quantitative difference in the relative amount of C gamma 4-encoded proteins was observed on Tcr gamma delta splenocytes from both newborn euthymic and adult athymic mice when compared to adult Tcr gamma delta splenocytes from euthymic mice. These results demonstrate that genetic polymorphisms exist among different mouse strains and suggest that selective developmental pressures may govern Tcr gamma delta expression. PMID- 2329010 TI - Inhibition of collagen II-induced arthritis in mice--a comparison of the effects of Sch 24937, immunosuppressants and nonsteroidal antiinflammatory drugs on the clinical expression of disease. AB - Previous studies from this laboratory have described Sch 24937 as a potent immunosuppressive agent that is particularly effective in suppressing humoral immune responses in mice. These findings prompted an evaluation of the effects of Sch 24937 in type II collagen-induced arthritis in mice where disease manifestations include the development of a strong humoral response to the collagen antigen. Sch 24937 reduced the incidence and severity of arthritis in collagen sensitized mice which appeared to be directly related to the immunosuppressive properties of the drug. However in contrast to the steroid betamethasone which also exhibited immunosuppressive activity, Sch 24937 did not prevent the changes occurring in the lymphocyte population of the draining lymph nodes of mice immunized with type II collagen. While the exact mechanism of the immunosuppressive activity of Sch 24937 remains to be elucidated, its mode of action in suppressing arthritis differs at least to some extent from that of a steroid. PMID- 2329011 TI - Control of human T cell proliferation by platelet-activating factor. AB - Platelet-activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF), is a membrane phospholipid with immunomodulatory functions. We studied the influence of PAF on mitogen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC), purified T cells and T cell subsets. High concentrations of PAF suppressed the proliferation of all cell populations studied (44% mean inhibition with 5 microM PAF and 78% inhibition with 10 microM PAF). In contrast, the deacetylated metabolite of PAF, lyso-PAF, had no effect on proliferation at micromolar concentrations. Lower, and presumably physiologically relevant, concentrations of PAF (10(-14) to 10(-8) M) stimulated a small increase in the proliferation of unfractionated T cells. When T cells were fractionated into CD4+ and CD8+ subsets, a difference in sensitivity to PAF was observed. PAF stimulated a modest, yet statistically significant, increase in the proliferation of CD4+ T cells at concentrations ranging from 10(-14) to 10(-10) M, while either having no effect or inhibiting the proliferation of CD8+ cells across the entire concentration range. Addition of indomethacin to the cultures further enhanced CD4+ proliferation, possible due to the blockade of PAF-induced PGE2 production by monocytes. The PAF receptor antagonist BN 52021 did not block the PAF effects in this system, and the PAF receptor antagonist SRI 63-675 caused a dose dependent inhibition of T cell subset proliferation. These findings suggest that while high concentrations of PAF suppress T cell proliferation, low concentrations selectively stimulate proliferation of the CD4+ subset, an effect which is partially counteracted by PAF-induced monocyte PGE2 production. PMID- 2329012 TI - A comparison of the effects of chlorpromazine and more selective histamine and 5 hydroxytryptamine antagonists on human IgG synthesis in vitro. AB - We have shown previously that chlorpromazine, a drug associated with immunological abnormalities in vivo, significantly potentiates pokeweed mitogen (PWM)-stimulated IgG synthesis by human peripheral blood mononuclear cells (PBMC) in culture. Chlorpromazine is a pharmacological antagonist of histamine and 5 hydroxytryptamine (5-HT) and thus may exert its immune-enhancing effects by competing with these amines for their respective receptors, which are known to be present on lymphocytes. In this report we show that histamine and 5-HT are present at micromolar concentrations in PBMC cultures. To examine the role of histamine and 5-HT in chlorpromazine-induced enhancement of IgG synthesis we incubated PWM-treated cells with a range of selective histamine and 5-HT antagonists, and with the amines added to cultures either alone or in combination with chlorpromazine. The H1 antagonists mepyramine and promethazine and the H2 antagonist cimetidine had no significant effect on IgG synthesis. The combined 5 HT1/5-HT2 antagonists methysergide and methiothepin also failed to modulate synthesis. Neither histamine nor 5-HT at concentrations up to 100 microM modulated IgG synthesis, nor did they abrogate the enhancement of IgG synthesis induced by chlorpromazine. We conclude that the modulation of IgG synthesis in vitro by chlorpromazine cannot be attributed to an interaction of this drug with lymphocyte receptors for histamine and 5-HT. Other possibilities for the mechanism of action of this drug on immune function are discussed. PMID- 2329013 TI - Modulation of the release of 9-hydroxy-octadecadienoic acid and other fatty acid derived mediators from guinea-pig pulmonary macrophages. AB - Non-stimulated guinea-pig pulmonary macrophages (PM) convert arachidonic acid to thromboxane B2 and 12-hydroxy-heptadecatrienoic acid, whereas linoleic acid is metabolized to two hydroxy compounds, i.e. 9-hydroxy- and 13-hydroxy octadecadienoic acid. Coincubation of PM with immune serum (2% v/v) resulted in a profound reduction of the release of these products. This effect seemed to be due to an inhibitory action on cyclooxygenase activity. Control serum also possessed inhibitory properties towards the release of fatty acid metabolites, possibly due to an effect on phospholipase activity. Because of the radical scavenging properties of 9-hydroxy-octadecadienoic acid, the modulation of the release of this product may be an important determinant in macrophage function. PMID- 2329014 TI - Pharmacokinetics of alkylating metabolites of cyclophosphamide in different strains of mice. AB - Determination of the amount of alkylating (NBP) metabolites of cyclophosphamide (CP) in blood serum of BALB/c and DBA/2 mice has revealed that the shape of the curve describing the accumulation of NBP-metabolites, depends on the administered drug dose and animals' genotype. The experimental data obtained made it possible to suggest an improved pharmacokinetic model which takes into account a possible switching in of factors conditioning non-linear changes in the intensity of the accumulation processes in blood and elimination of CP alkylating metabolites from blood. The effect of different CP alkylating metabolite kinetics in BALB/c and DBA/2 mice on a different sensitivity of these mice to the immunodepressive action of CP in vivo, has been discussed. PMID- 2329015 TI - Selective killing of tumor cells in vitro by an immunotoxin composed of ricin and monoclonal antibody against Ia antigen. AB - A monoclonal antibody (MAb-HB55) directed against a HLA class II antigen (Ia), was purified by DE-52 chromatography. The purified MAb contained less than 5% impure protein detected by SDS-PAGE. Ricin was conjugated with the MAb via a disulfide bond to construct an immunotoxin (ricin-HB55). The concentration causing fifty percent growth inhibition (IC50) was 2 x 10(-11)M for the Raji cells. In contrast, the IC50 for Molt-4 and K562 cells was 100 times higher than that for the Raji cells. B lymphocytes separated from peripheral blood lymphocytes by nylon wool were selectively killed by the conjugate, but T lymphocytes were not apparently affected. Our results demonstrate that the immunotoxin is selectively cytotoxic to Raji cells and B-cells, and may have potential for purging malignant cells from bone marrow of patients with B-cell leukemia and lymphoma. PMID- 2329016 TI - Steroidal glycolipid, L-644,257, is a potent enhancer of nonspecific host resistance. AB - A steroidal glycolipid that enhances the nonspecific cellular response to opportunistic infection in an immunocompromised host has been discovered. A dose dependent response with 6-(5-cholesten-3 beta-yloxy)hexyl 1-thio-beta-D mannopyranoside, L-644,257, was observed against several infective agents including bacterial, fungal, and viral pathogens in cyclophosphamide-treated mice. A mechanism for this protective action is proposed. PMID- 2329017 TI - Ablation of natural killer cell function by soluble cardiotoxin. AB - A one-hour preincubation of nonadherent murine spleen cells with a soluble membrane-active cardiotoxin purified from the venom of the Thailand cobra Naja naja siamensis results in the destruction of natural killer (NK) cell activity against YAC-1 target cells in a dose-dependent manner. Prior in vivo induction of interferon production by polyinosinic/polycytidylic acid does not avert the cardiotoxin inhibition of NK function. Loss of complement-mediated lysis of cells capable of binding an NK-1.1 monoclonal antibody suggests that the cardiotoxin directly affects the integrity of the NK cell plasma membrane. Cardiotoxin which has been adsorbed to the surface of polystyrene tissue culture plates retains the ability to lyse splenic T lymphocytes, but loses the ability to interfere with NK activity, as measured either by the release of 51Cr or by the uptake of 3H thymidine by the target lymphoma cells, suggesting that different parts of the cardiotoxin molecule are responsible for destruction of the two types of lymphocytes. PMID- 2329018 TI - Effect of ketotifen on antigen-induced interleukin 2 (IL-2) responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma. AB - We tested the effect of Ketotifen (4-(1-methyl-4-piperidylidene)-4H- benzo[4,5] cyclohepta[1,2-b]thiophen-10(9H)-one hydrogen (fumarate) on the induction of allergen-induced IL-2 responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma. Ovalbumin (OVA)- and/or Dermatophagoides farinae(Df)-induced IL-2 responsiveness was increased in almost all patients (1 15 years old) before Ketotifen treatment. Two to 12 months administration of Ketotifen (0.06 mg/kg/day) decreased activity of the response in 7 out of 9 cases corresponding to improvement of clinical symptoms. In in-vitro studies, antigen presenting cells (adherent cells) from the patient pretreated with 5, 50 and 500 ng/ml doses of Ketotifen for 12 h failed to present OVA or Df antigen to T-cells for induction of IL-2 responsiveness. Antigen-pulsed adherent cells also failed to induce the response of the T-cells pretreated with 50 and 500 ng/ml doses of Ketotifen but not with a 5 ng/ml dose. A 50 ng/ml dose of Ketotifen did not affect T-cells for induction of the response. In contrast, the treated adherent cells are capable of presenting PPD antigen or Con A for the induced response. The combined data indicate that induction of IL-2 responsiveness of peripheral blood lymphocytes on stimulation with nominal antigen may reflect an immune response to allergen in patients with allergy and a weak immunosuppressive effect of Ketotifen seems to block the response in the pathogenic process of allergic diseases. PMID- 2329019 TI - IgG2b-dependent down regulation of the LPS-induced PFC-response and its blockade by Fc gamma 2bR protein. AB - Fc gamma receptor (Fc gamma R)-dependent immunoregulation by murine heat aggregated (HAgg) IgG subclasses on the bacterial lipopolysaccharide (LPS) induced plaque forming cell (PFC) response to trinitrophenylated sheep red blood cell (TNP-SRBC) antigen and the competitive effect by Fc gamma 2bR-protein on the down regulation by HAgg-IgG2b were studied in murine T-cell-deprived spleen cell cultures. HAgg-IgG1 and HAgg-IgG3 enhanced the PFC response, but HAgg-IgG2b strongly suppressed the LPS-induced PFC response. HAgg-IgG1 could not compete with the suppressive effect of HAgg-IgG2b. The HAgg-IgG2b seemed to act on both macrophages (M phi) and B-cells, because the cell cultures that had been reconstituted with HAgg-IgG2b-pretreated M phi and untreated B-cells and vice versa showed poor PFC responses. The suppression induced by HAgg-IgG2b on the LPS induced PFC response in the T-cell-deprived cultures was abolished by the addition of phospholipase C (PLC)-treated Fc gamma 2bR protein at the early stage of the culture. The mechanisms by which HAgg-IgG2b suppress the LPS-induced PFC response and PLC-treated Fc gamma 2bR protein restores this response were discussed. PMID- 2329020 TI - Generation of tumoricidal effector cells with a novel potentiator: N-[4-[(4 fluorophenyl)sulfonyl]phenyl] acetamide (CL 259,763). AB - An effort was made to investigate the effects of a novel immunopotentiator, N-[4 [(4-fluorophenyl)sulfonyl]phenyl]acetamide (CL 259,763), on the generation of tumoricidal effector cells. It was demonstrated that a single oral dose of the compound (100-600 mg/kg) induced in mice a population of peritoneal macrophages capable of inhibiting the growth of tumor cells. These activated macrophages released proteases which seemed responsible for the tumor cell inhibition because the cytostatic activity was abrogated in the presence of protease inhibitors TLCK and aprotinin. On the other hand, addition of catalase and exogenous arginine to the culture failed to alter the effect, suggesting that hydrogen peroxide and arginase did not participate in this system. Although induction of cytolytic T lymphocytes (CTL) reactive with syngeneic tumor cells was achievable in mice previously sensitized to the tumor, treatment with CL 259,763 rendered these animals even more responsive to tumor antigens resulting in a significant enhancement of tumor cell destruction. The compound was effective in augmenting the CTL response over a rather broad dose range of 25-200 mg/kg. In contrast to these stimulatory effects, the cytolytic activity of natural killer cells seemed not to be affected by the compound. Taken together, CL 259,763 is an orally active immunomodulator capable of inducing tumor inhibitory macrophages and potentiating CTL responses to syngeneic tumor cells and, therefore, may prove clinically useful in the treatment of neoplastic diseases. PMID- 2329021 TI - Naphthalene derivatives that selectively inhibit an antigen-specific IgE response in murine lymphocytes. AB - When the spleen cells from BALB/c mice that had been immunized twice with TNP-KLH were cultured with the same antigen, the synthesis of anti-TNP IgE as well as anti-TNP IgG was induced. We found that the addition of a naphthalene derivative, (E)-N-(2-methoxy-carbonylphenyl)-8-(2-naphthyl)-5,6-trans-5,6-meth ano-7- octenamide (TEI-1338) or methyl-6,7-dihydroxy-2-naphthylthioacetate (TEI-3332) to this lymphocyte culture system resulted in a marked suppression of anti-TNP IgE response without affecting the corresponding IgG production. These compounds are expected to be a prototype for the drug that can be used for the treatment of IgE mediated allergic diseases. PMID- 2329022 TI - Triethyllead-induced inhibition of proliferation of normal human lymphocytes through decreased expression of the Tac chain of interleukin 2 receptor. AB - Triethyllead (Et3Pb+) in concentrations 10(-5) to 10(-6) M has been shown to inhibit several key cellular molecular systems. In order to evaluate the effect of Et3Pb+ on the human immune system, the mitogen-induced cell proliferation of peripheral blood mononuclear cells was studied in the presence of Et3Pb+. Preincubation of normal T-lymphocytes with 10(-6) M Et3Pb+ for 1-4 h, which has been shown to be non-cytotoxic, was sufficient to inhibit subsequent mitogenic induced cell growth. The Et3Pb(+)-induced impairement of the in vitro proliferation of mitogen-activated normal T-cells was due to a dose-dependent decreased expression of the p55 polypeptide chain (Tac molecule) of the interleukin-2 receptor (IL-2-R), which could not be enhanced by exogeneously added recombinant interleukin 2 (rIL-2). Conversely, the same concentrations of Et3Pb+ could not inhibit the mitogen-induced expression of MHC class II molecules and the transferin receptor on activated T-cells. The impaired membrane expression of p55 on T-cells induced by Et3Pb+ was due to a decrease of Tac mRNA transcripts as showed by Northern blot analysis. This effect seems to be specific since in parallel experiments Et3Pb+ could not inhibit both the accumulation of actin mRNA and the production of IL-2 by Et3Pb(+)-treated mitogen-activated cells. The effect of this organolead compound was also associated with a dose dependent decrease of the Na(+)-K(+)-ATPase activity of normal lymphocytes. These results indicate that Et3Pb+ could affect specifically T-cell proliferative responses through an imbalance of the IL-2/IL-2-R system. PMID- 2329023 TI - Cutaneous infections in Trinidad. AB - Skin infection is common in patients with any skin diseases where pruritus is a prominent feature. A retrospective analysis was performed on the results of skin swab cultures from patients with eczema and a variety of other conditions. This paper presents the findings of bacteriologic culture and sensitivity testing of 131 swabs from 122 patients over a period of 22 months and examines the results in terms of the reported relationship between scabies and acute poststreptococcal glomerulonephritis. Staphylococcus aureus was most often isolated, and this appears to indicate that antistaphylococcal antibiotics should be the first line of treatment in the absence of the results of cultures. PMID- 2329024 TI - Determination of different populations of blood lymphocytes in Brazilian patients with hanseniasis. AB - The number of B and T lymphocytes were determined in the blood of 35 Brazilian patients with leprosy: 19 lepromatous (L), 9 borderline (B), 4 tuberculoid (T), and 3 indeterminate (I) and also in a control group of 30 normal individuals. The results, were as follows. B lymphocytes, no differences between the patients with hanseniasis and the control group; T lymphocytes, there was an evident depletion in the patients with L compared to the control group and patients with T; and the average of T lymphocytes in B and I was lower than that seen in the control group and in patients with T. Despite this alteration they approach to what is found in the patients with T and the control group. PMID- 2329025 TI - Psoriasis without neutrophils. AB - Histologic studies suggest that polymorphonuclear leukocytes (polys) may initiate, enable, and/or enhance the development of psoriasis. A man with long standing psoriasis developed acute myelogenous leukemia. His psoriasis disappeared after treatment with daunorubicin and cytosine arabinoside. Smears of his peripheral blood showed essentially zero polys from day 10 to day 22 after start of chemotherapy. His psoriasis began to reappear on day 14, became prominent by day 16, and persisted. Polys may not be requisite for the development and maintenance of psoriasis. PMID- 2329026 TI - Contact dermatitis from a subclavian catheter. PMID- 2329027 TI - Koebner phenomenon in a diabetic with necrobiosis lipoidica diabeticorum. PMID- 2329028 TI - Pretibial myxedema localized to scar tissue. PMID- 2329029 TI - Plastibase: a new base for patch testing of metal antigens. PMID- 2329030 TI - Onchocerciasis: an unusual presentation as eczema. PMID- 2329031 TI - Dermatoses of the umbilicus. PMID- 2329032 TI - Factitial dermatitis induced by application of garlic. PMID- 2329034 TI - Preoperative prediction of postoperative complications. PMID- 2329033 TI - Antithrombin III and preeclampsia. PMID- 2329035 TI - Clinical and epidemiological significance of species identification of coagulase negative staphylococci in a microbiological laboratory. AB - Although coagulase-negative staphylococci have been implicated in certain human infections, they are generally regarded as contaminants and their clinical significance has been questioned. To assess their role as pathogens, we studied 203 isolates of coagulase-negative staphylococci cultured from blood, wounds, body fluids (pleural, peritoneal and cerebrospinal), urine, and catheter tips. Patients' charts were reviewed and the clinical significance of these isolates was determined. Staphylococcus epidermidis accounted for 48% of isolates, S. hemolyticus for 33%, and other species (including S. capitis, S. hominis, S. warneri, S. cohnii, S. simulans, S. xylosus and S. saprophyticus) for the remaining 19%. There was no correlation between the pathogenicity and the species isolated, the source it was isolated from, or the pattern of antibiotic susceptibility. These observations suggest that identification of coagulase negative staphylococcal species may be of limited value in predicting clinical significance. PMID- 2329036 TI - Clonal heterogeneity in populations of Leishmania major. AB - Forty clones of Leishmania major were derived by direct plating from lesions and from cultures of recent isolates, followed by plating as well as by additional limit dilution in some. The parental strains originated from and represented three geographical areas in each of which a distinct electrophoretic type of the enzyme 6-phosphogluconate dehydrogenase (6PGD) is found. Each clone was characterized in terms of its virulence in Sabra mice, morphology, serotype, enzyme electrophoretic profile based on 11 enzymes, and kinetoplast DNA endonuclease restriction pattern. All the clones showed a similar virulence in the mice and similar polymorphism in fresh drops of living cultures and in Giemsa stained preparations. Ten clones from the Jordan Valley were all serotype A1, 15 clones from the Arava were all A1Bz--confirming the mixed serological nature of parasites from this region, 11 of the 20 clones from the western Negev-eastern Sinai included a new A subserotype, and 9 were A1. Generally, the geographical separation of the 6PGD variants was upheld. Two of the Jordan Valley clones were similar to those of the western Negev. On two occasions, different enzyme types were isolated from the same individual, in one case from the same lesion. All clones from the western Negev were alike and similar to the type previously found in that region. The situation in the Arava was more complicated, since clones representative of all three regional types were found. In cases where the first two types were found, the clones and their parental strains were similar. However, one parental culture yielded three clones that resembled the reference strain for the Jordan Valley and two which resembled that of the western Negev. In one of these cases, two dissimilar clones originated from the same lesion. One aberrant clone from the western Negev was variant for nucleoside hydrolase. The kinetoplast DNA of each clone was distinct but relatively complicated, which made differentiation of these regional types difficult. However, clones from the same area displayed more similarity to each other than to those of other regions, implying a closer genetic relationship. PMID- 2329037 TI - Antithrombin III levels in preeclampsia. AB - Antithrombin III (AT-III) activity was measured and compared in 29 patients with preeclampsia and 31 women with normal pregnancies. AT-III levels were 83 +/- 25% in preeclamptic patients with greater than 5 g/l proteinuria compared with 102 +/ 11% in the controls. Less severe proteinuria was not associated with decreased AT-III levels. Multivariate analysis revealed that the duration of pregnancy and the degree of proteinuria had an independent negative effect on AT-III levels. AT III activity correlated poorly with platelet counts and blood pressure measurements. We conclude that urinary loss appears to be the major mechanisms of lower AT-III levels observed in our patients with preeclampsia. PMID- 2329038 TI - Long-term follow-up of patients after pyeloplasty for ureteropelvic junction obstruction. AB - Between the years 1976 and 1986, 94 patients ranging in age from 2 weeks to 60 years were referred for treatment of ureteropelvic junction obstruction. A dismembered pyeloplasty was performed in 85 patients, ureterocalycostomy in 4 patients and primary nephrectomy in 5 patients. Apart from aberrant vessels found in 14 patients and associated calculi in 12, clinical results were satisfactory in most of the patients (96.2%). The calyceal appearance on the postoperative excretory urogram showed diminution with good drainage in 53.8%, improvement of drainage in 42.3%, and deterioration in 3.8%. PMID- 2329039 TI - Preoperative prediction of postoperative complications. AB - The value of history taking, physical examination and routine laboratory tests as predictors of postoperative complications was investigated in 100 patients undergoing major surgery. Major and minor risk markers were identified and compared with major and minor postoperative complications. The results proved this approach to be a simple, inexpensive and reliable method for the prediction of postoperative complications. PMID- 2329040 TI - Childhood mortality from accidents in Israel, 1980-84. AB - There were on average 1.5 million children aged 0-17 in Israel during the period 1980-84, with an average accidental mortality rate of 10.9/100,000. Although 77% of the children were Jewish and 23% non-Jewish, 45% of the accidental deaths occurred in the non-Jewish population. The accidental mortality rate among non Jewish children was 20.9/100,000, which was 2.6-fold greater than that among Jewish children (7.9/100,000). Among both population groups, the male death rates were considerably higher than the female rates (10.5 vs. 5.1 among Jewish males and females, respectively, and 25.1 vs. 16.5 among non-Jewish children). The non Jewish death rates were highest among infants less than 1 year of age, with females outnumbering males. Inspection of the male to female rate ratios showed a greater disparity between the sexes in both population groups as age increased. The proportion of motor vehicle accident (MVA) deaths was 52.7% among Jews and 40.4% among non-Jews. Drowning was the second ranking cause of accidental death (approximately 15%) in Israeli children, followed by falls (approximately 8%). The age distribution of MVA mortality was strikingly different in the two Israeli population groups. Among the Jews the rates peaked in the 15-17 age group in both sexes; however, among the non-Jews the rates peaked in the 1-4 age-group, with most of these deaths probably representing pedestrian deaths. On the average, the MVA serious injury rates were about ten times greater than the MVA mortality rates. Variations of mortality from accidents in different age, sex and population groups clearly indicate that preventive intervention programs must be targeted specifically to each age-sex-population group. PMID- 2329041 TI - Allergic vasculitis and the mast cell degranulation test. PMID- 2329042 TI - Stomach rupture caused by false intubation of the esophagus. PMID- 2329043 TI - 19th annual meeting of the Israel Immunological Society. May 1989, Rehovot, Israel. Abstracts of papers. PMID- 2329044 TI - Closed-chest electrical ablation (fulguration) of atrioventricular accessory pathway in the Wolff-Parkinson-White syndrome: report of the first case in Hawaii. AB - Wolff-Parkinson-White (WPW) syndrome is a condition characterized by the presence of an atrioventricular (AV) accessory pathway or bypass tract, which is an extraneous piece of muscular tissue connecting atrium to ventricle. This pathway leads to characteristic findings on the electrocardiogram (EKG). Patients with this syndrome are often asymptomatic, but many frequently have various forms of tachyarrhythmias, some of which may be life-threatening. The conventional therapy is medical, by suppression with antiarrhythmic agents. The established alternative to medical therapy has been surgery, with open-chest excisional ablation of the accessory pathway. In experienced centers, this has a high success rate and holds the promise of cure. Unfortunately, it requires thoracotomy, with its not insignificant associated surgical morbidity. PMID- 2329046 TI - Thirty-fifth annual meeting of the Health Physics Society. June 24-28, 1990, Anaheim, California. Abstracts. PMID- 2329045 TI - Rabies prevention in Hawaii. AB - The scientific basis of Hawaii's public health rabies prevention program is discussed, as is a proposed minor modification offered to assist Hawaii residents who use guide dogs and who want to travel out of state. Hawaii's current quarantine program has successfully prevented the introduction of the disease. Alternative programs involve risks that are not easily evaluated. PMID- 2329047 TI - Use of telephone interviewing in health care research. AB - Increasingly, telephone interviewing has become the data collection procedure of choice in large-scale health services research surveys. Previous analyses indicate that excluding nontelephone households does not seriously affect most national parameter estimates, such as yearly estimates of number of ambulatory visits, mainly because the proportion of households without telephones is small. Moreover, if the exclusion of nontelephone households simply underestimates the proportions in the population with certain characteristics, such as age and ethnicity, and the "true" proportions are known, it is possible to appropriately weight the study group in order to mitigate the telephone-exclusion bias. However, regression analyses undertaken on three years of national Health Interview Surveys indicate, at least on some key measures such as having health insurance, that persons living in households with and without telephones represent different populations, and parameter estimates are distorted by excluding nontelephone households. Under these circumstances, it is not possible to adjust parameter estimates to take into account nontelephone households. PMID- 2329048 TI - The attitudes of physicians toward health care cost-containment policies. AB - This study analyzed physician attitudes toward a variety of health care cost containment policies, based on a national survey of 500 practicing doctors in 1984. Reactions to 23 policies were simplified to nine common themes using factor analysis. Although there was great diversity in views, physicians generally favored policies that increased responsibilities or costs for patients and disfavored policies that decreased physicians' autonomy of practice. For most policies, practice characteristics (specialty; type of practice, e.g., solo or group, salaried or self-employed; membership in medical societies; or percent of time in direct patient care) were not significant determinants of attitudes. Physicians who were more "conservative" with respect to the health care system tended to favor policies that shifted cost to patients, while more "liberal" doctors were more supportive of using prepaid health care, reducing the intensity of care, or selecting efficient providers. Overall, this study indicates that physicians still place a high value on their professional autonomy. PMID- 2329049 TI - Physician adaptation to health maintenance organizations and implications for management. AB - The growth of health maintenance organizations (HMOs) and other forms of managed care presents a challenge to traditional patterns of private practice. In Dane County, Wisconsin (Madison Metropolitan Area), the proportion of the population enrolled in closed-panel HMOs increased dramatically, from 10 percent in 1983 to over 40 percent by 1986. This study surveyed 850 practicing physicians regarding their expectations before, and experiences after this rapid change to competitive HMOs. Although most physicians expected a loss of earnings and lower-quality care, the majority reported that neither declined. However, most physicians expected and reported a decline in their autonomy. Primary care physicians were most supportive of the change to HMOs. The implications of these findings for management practices are discussed. PMID- 2329050 TI - Explaining trends in use of VA inpatient psychiatric services. AB - We examined the expansion of Veterans Administration (now Department of Veterans Affairs--VA) inpatient psychiatric services from 1963 to 1984. Aggregate national trends in VA inpatient episodes between 1963 and 1984 document not only increased use of inpatient services but also "decentralization," or a shift to providing psychiatric services in general VA medical centers. The national trends show a dramatic increase in admissions to psychiatric bed sections over the period 1963 1978, with admissions staying at this high level from 1976-1981 and dropping only slightly in the 1980s. Admission trends were disaggregated into first admissions and readmissions to psychiatric and general hospitals in a single VA medical district for the period 1972-1981. First admissions declined over the study period for both hospital types; readmissions increased initially, but declined somewhat at the end of the period. The admission trends and patterns in source of first admissions suggest that the growth of VA services reflects psychiatric "decentralization," as well as deinstitutionalization within VA. PMID- 2329051 TI - Influence of colonizing micro-flora on the mucin histochemistry of the neonatal mouse colon. AB - Mucin histochemistry on sections of colon from germ-free and conventional mouse pups showed that all goblet cell mucins were sulphated at birth. During the first two weeks of post natal development, the pattern of mucin production in the ascending colon changed to a distribution of non-sulphated mucins towards the apical zone of the crypts and sulphated sialomucins basally. In conventional animals during the third postnatal week when the complex micro-flora of the colon was becoming established, the typical adult mucin distribution pattern developed, with sulphated mucins now confined to the upper third of the crypt. However, in the absence of a colonizing micro-flora crypt mucins become more and more sulphated until at weaning, most goblet cells of the ascending colon were producing fully or partially sulphated mucins, except for one or two cells at the very base of the crypt. PMID- 2329052 TI - Mitochondrial alpha-glycerol phosphate dehydrogenase activity in IIA fibres of the rat lateral gastrocnemius muscle; the effect of Ca2+ and ATP. AB - Mitochondrial alpha-glycerol phosphate dehydrogenase is an important enzyme, but it is difficult to extract and purify. We have measured the activity of this enzyme in single type IIA skeletal muscle fibres under initial rate conditions by microdensitometry of the formazan reaction product. The Km (1.6 mM) for the substrate (L-alpha-glycerol phosphate) was lower than reported for the extracted enzyme. Further, at low substrate concentrations (3 mM), the enzyme was allosterically activated by free Ca2+ concentrations of 1 microM or greater, and half-maximal stimulation occurred at 0.3 microM free Ca2+. In the absence of Ca2+, there was negative cooperativity of substrate binding with a Hill constant of 0.57, but no cooperativity occurred in the presence of calcium. ATP (10 mM) inhibited enzyme activity in the presence of Ca2+ but not in its absence. PMID- 2329053 TI - Ultrastructural localization of endogenous calcium in the teleost retina. AB - The ultrastructural localization of endogenous calcium in the retina of adult cichlid fish Oreochromis mossambicus (Teleostei) was studied using the cytochemical osmiate-bichromate method of Probst (1986). The specificity of this method for calcium localization was proven by means of EGTA treatment of ultrathin sections and electron-spectroscopic-imaging technique (ESI) with an energy-filtering transmission electron microscope (CEM 902, Zeiss). Large amounts of electron-dense calcium containing deposits were found in the outer segments of rods, in the synaptic vesicles of receptor terminals and bipolar cells, in the perinuclear space of photoreceptors and in the endoplasmic reticulum of different cell types, especially in the inner segment and fibres of photoreceptor cells. In the inner plexiform layer calcium was detected in the extracellular space with greater accumulations in the synaptic cleft. Principal differences in the localization of calcium between rods and cones and between several types of synapses and vesicles are shown. The possible role of calcium in the subcellular structures of retinal cells is discussed. PMID- 2329054 TI - Histochemical studies of intestinal epithelial goblet cell glycoproteins during the development of the human foetus. AB - Histochemical studies performed on specimens of intestine from 12 to 37-week human foetuses showed that the epithelial glycoproteins of the goblet cells of the small intestine are non-sulphated sialoglycoproteins containing neutral sugar (hexose, 6-deoxy hexose or N-acetyl hexosamine residues with Periodic acid-Schiff (PAS) reactive vicinal diols), sialic acids without O-acyl substituents, smaller and variable quantities of sialic acids with O-acyl substituents at positions C8 or C9 (or with two or three side chain substituents) and O-acyl sugars (neutral sugars with an ester substituent blocking PAS reactivity). In the lower small intestine glycoproteins containing 8 (or 9)-O-acyl sialic acids are first observed in goblet cells at the tips of the villi. As the foetus matures their quantity increases and they are found in goblet cells located along the length of the villi. Smaller quantities of O-acyl sialic acids and traces of O-acyl sugars occur in the goblet cells of the upper small intestine. The colonic goblet cells contain sulphosialoglycoproteins of two types. The first type, found in the majority of specimens, contains O-sulphate ester, neutral sugar, O-acyl sugars and 8 (or 9)-O-acyl sialic acids. The second type contains O-sulphate ester, neutral sugars, and sialic acids which are either without side chain O-acyl substituents or are a mixture of such acids and 8 (or 9)-O-acyl sialic acids; O acyl sugars are reduced or absent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329055 TI - Origin of intrafusal muscle fibers in the rat. AB - The expression of several isoforms of myosin heavy chain (MHC) by intrafusal and extrafusal fibers of the rat soleus muscle at different stages of development was compared by immunocytochemistry. The first intrafusal myotube to form, the bag2 fiber, expressed a slow-twitch MHC isoform identical to that expressed by the primary extrafusal myotubes. The second intrafusal myotube to form, the bag1 fiber, expressed a fast-twitch MHC similar to that initially expressed by the secondary extrafusal myotubes. At subsequent stages of development, the equatorial and juxtaequatorial regions of bag2 and bag1 intrafusal myofibers began to express a slow-tonic myosin isoform not expressed by extrafusal fibers, and ceased to express some of the MHC isoforms present initially. Myotubes which eventually matured into chain fibers expressed initially both the slow-twitch and fast-twitch MHC isoforms similar to some secondary extrafusal myotubes. In contrast, adult chain fibers expressed the fast-twitch MHC isoform only. Hence intrafusal myotubes initially expressed no unique MHCs, but rather expressed MHCs similar to those expressed by extrafusal myotubes at the same chronological stage of muscle development. These observations suggest that both intrafusal and extrafusal fibers develop from common pools of bipotential myotubes. Differences in MHC expression observed between intrafusal and extrafusal fibers of rat muscle might then result from a morphogenetic effect of afferent innervation on intrafusal myotubes. PMID- 2329056 TI - Regional differences in the distribution of endogenous receptors for carbohydrate constituents of cellular glycoconjugates, especially lectins, in cortex, hippocampus, basal ganglia and thalamus of adult human brain. AB - Ten different types of labelled neoglycoproteins, exposing glycohistochemically pivotal carbohydrate moieties that mostly are constituents of naturally occurring glycoconjugates with an aromatic spacer, were synthesized. The panel was applied to fixed, paraffin-embedded sections of different cortical regions and white matter, of hippocampal gyrus, basal ganglia, thalamus nuclei and adjacent areas of adult human brain to comprehensively map the presence of respective binding sites in these parts. Compliance with accepted criteria for specificity of binding was routinely ascertained. Overall, not a uniform binding pattern, but a distinct distribution with regional differences on the level of specific cytoplasmic and nuclear staining in nerve cells was determined, fiber structures being generally labelled with medium or strong intensity. For example, among the neurons localized in the five cortical laminae the binding of N-acetyl-D galactosamine varied from strong to undetectable. Biochemical analysis, employing carbohydrate residues as affinity ligands in chromatography, proved that the neuroanatomically different regions exhibited a pattern of receptors with notable similarities. These results on endogenous binding sites for glycoconjugates, especially lectins, are complementary to assessment of localization of cellular glycoconjugates by plant lectins and carbohydrate-specific monoclonal antibodies. They are thus a further obligatory step to substantiate the physiological roles of recognitive protein-carbohydrate interactions in the central nervous system. PMID- 2329057 TI - Secretin-cells of the mammalian intestine contain serotonin. AB - Various endocrine cells contain biogenic amines in addition to their peptide hormones. In the digestive tract, one of these amines is serotonin that is regularly present in enterochromaffin (EC-) cells. Previously, it has been assumed that other entero-endocrine cell types also contain this amine. Moreover, it was presumed that chromogranin A, an acidic glycoprotein, is involved in storage mechanisms for biogenic amines in endocrine cells. Using immunohistochemical techniques, we now exemplarily investigated cholecystokinin (CCK-) and secretin (S-) cells of five adult mammalian species for their content of serotonin and of chromogranin A. In all mammalian species, CCK-cells were devoid of serotonin but contained chromogranin A immunoreactivity of varying densities. In contrast, S-cells of all mammals were immunoreactive for serotonin; however, immunoreactivities for this biogenic monoamine were heterogeneous and varied from dense to faint or lacking immunostainings. Likewise, immunoreactivities for chromogranin A in S-cells showed inter-species and inter cellular heterogeneities. S-cells containing serotonin were simultaneously immunoreactive for chromogranin A and the density of immunoreactivities for both were correlated in given S-cells. Based on mutual relationships of chromogranin A and serotonin immunoreactivities, we assume that chromograinin A is virtually a prerequisite for the S-cells' content of serotonin and that this protein participates in storage mechanisms for biogenic amines in endocrine cells. S cells have now to be added to the family of amine-storing endocrine cells. Basically, serotonin-storing endocrine cells in the digestive tract cannot be simply regarded as enterochromaffin (EC-) cells any longer; the current nomenclature and classification of entero-endocrine cells should be reviewed in this respect. PMID- 2329058 TI - Secretory glycoproteins of the rat subcommissural organ are N-linked complex-type glycoproteins. Demonstration by combined use of lectins and specific glycosidases, and by the administration of Tunicamycin. AB - Two experimental protocols were used to investigate the secretory glycoproteins of the subcommissural organ (SCO). Protocol I: Lectins, specific exoglycosidases and immunocytochemistry were sequentially applied to the same section or to adjacent semithin sections of the rat SCO fixed in Bouin's fluid and embedded in methacrylate. Lectins used: concanavalin A (con A), wheat germ agglutinin, Limulus polyphemus agglutinin, Ricinus communis agglutinin and Arachis hypogeae agglutinin. Glycosidases used: neuroaminidase, beta-galactosidase, alpha mannosidase, alpha-glucosidase and beta-N-acetyl-glucosaminidase. For immunocytochemistry an antiserum against bovine Reissner's fiber (AFRU) was used. Lectins and glycosidases were used in sequences that allowed the cleaved sugar residue to be identified as well as that appearing exposed as a terminal residue. This approach led to the following conclusions: (1) the terminal sugar chain of the secreted glycoproteins has the sequence sialic acid-galactose-glucosamine-; (2) the con A-binding material present in the rough endoplasmic reticulum corresponds to mannose; (3) the apical secretory granules and Reissner's fibers displayed a strong con A affinity after removing sialic acid, thus indicating the presence of internal mannosyl residues in the secreted material; (4) after removing most of the sugar moieties the secretory material continued to be strongly immunoreactive with AFRU. Protocol II: Rats were injected into the lateral ventricle with Tunica-mycin and killed 12, 24, 50 and 60 h after the injection. The SCO of rats from the last two groups showed a complete absence of con A binding sites. The results from the two experiments confirm that the secretory glycoproteins of the rat SCO are N-linked complex-type glycoproteins with the conformation previously suggested (Rodriguez et al. 1986). PMID- 2329059 TI - GABA-immunohistochemistry as a label for identifying types of local interneurons and their synaptic contacts in the antennal lobes of the American cockroach. AB - Synaptic contacts between GABA-immunoreactive neurons, antennal receptor fibers and non-GABA-immunoreactive neurons in the glomerular neuropil of the antennal lobes have been identified by means of a combination of (i) immunohistochemical labeling and (ii) labeling of afferent fibers of the antenna by experimentally induced degeneration. Characteristic contacts of these neurons are: a) Serially arranged polysynaptic contacts between degenerated antennal fibers, GABA immunoreactive neurons and non-GABA-immunoreactive neurons. b) Monosynaptic contacts between degenerated antennal fibers and non-GABA-immunoreactive neurons. c) Reciprocal synaptic contacts between immunostained and non-stained neurons and synaptic contacts between individual GABA-immunoreactive neurons. d) Synaptic output contacts of GABA-immunoreactive neurons with degenerated antennal fibers. GABA-immunoreactive neuron profiles in the glomeruli are assigned to multiglomerular local interneurons (Distler 1989a); non-immunolabeled profiles may be assigned to projection neurons and other not yet identified interneurons. PMID- 2329060 TI - Immunocytochemical determination of ploidy class-dependent bromodeoxyuridine incorporation in rat liver parenchymal cells after partial hepatectomy. AB - Immunocytochemistry of bromodeoxyuridine (BrdU) incorporated in DNA was performed on cryostat sections of rat liver and on isolated hepatocytes after partial hepatectomy using a two-step labeling technique. The method enabled the detection of S-phase nuclei in both tissue preparations. Quantification of the number of labeled nuclei in sections showed that the number of nuclei in S-phase increased from 0.3% in control liver to about 36% at 24 h after partial hepatectomy. The detection of BrdU in isolated hepatocytes showed the same labeling index of binuclear diploid, mononuclear tetraploid and binuclear tetraploid cells. A special role for mononuclear diploid cells in proliferation did not seem to occur. PMID- 2329061 TI - Bromodeoxyuridine (BrdUrd) immunohistochemistry in undecalcified plastic-embedded tissue. Elimination of the DNA denaturation step. AB - We examined the application of BrdUrd immunohistochemistry to detect S-phase cells in undecalcified bone and cartilage from the growing rat embedded in Spurr's resin. The effect of fixation on the procedure was studied, and the validity of the technique examined by a comparative study with tritiated thymidine ([3H]-TdR) autoradiography. The use of sodium-ethoxide to remove plastic from tissue sections prior to immunohistochemistry resulted in the production of sufficient ssDNA to make a separate DNA denaturation step unnecessary, thus sparing sections from potentially destructive treatment and shortening the immunohistochemical procedure. Fixation in formalin or Bouin's fluid gave the most satisfactory results. The distribution of BrdUrd labeled cells was restricted to the sites of cell proliferation in growing long bones. Combined studies with BrdUrd immunohistochemistry and [3H]-TdR autoradiography showed that the majority of BrdUrd labeled cells had also incorporated [3H]-TdR, thus attesting to the validity of the technique. This novel approach is suitable for the study of undecalcified hard tissues as well as soft tissues. PMID- 2329062 TI - Immunohistochemistry of endogenous L-DOPA in the rat posterior hypothalamus. AB - The aim of this work was to study L-DOPA-containing neuronal structures of the rat posterior and dorsal hypothalamus by means of immunohistochemistry using antiserum against glutaraldehyde conjugated L-DOPA. Aspects and distribution of L DOPA immunoreaction among cells of the supramammillary nucleus and the A11, A13c and A13 cell groups are described and compared to dopamine immunoreactivity, mainly through a double colored labelling procedure employing a color modification of the DAB reaction by metallic ions. Differences between L-DOPA and dopamine stainings within cell groups as the presence of cells with predominant or exclusive L-DOPA coloration are tentatively explained under the light of previous findings using immunohistochemistry of catecholamines synthesizing enzymes and catecholamines histofluorescence. PMID- 2329063 TI - Expression of villin in the mouse oviduct and the seminiferous ducts. AB - Villin, a 95-kD cytoskeletal protein selectively expressed in the microvilli of some absorptive cells was localized immunohistochemically in the oviduct and the seminiferous excretory ducts of the mouse. Villin was found in the proximal part of the oviduct, comprising the preampulla, ampulla, and part of the isthmus. Distal to the isthmus the oviductal cells lining the junctura and the intrauterine colliculus tubaris were devoid of villin. No villin could be detected in the uterine cells. Ductuli efferentes, connecting the rete testis with the epididymis were the only portion of the male seminiferous ductal system expressing villin. The cells lining the epididymis and the vas deferens were devoid of villin. These data show that villin is selectively expressed in male and female reproductive systems and that it is limited to anatomically defined proximal portions of the reproductive ducts. PMID- 2329064 TI - Comments on accreditation process. PMID- 2329065 TI - Still more on Tufts' student surgery program. PMID- 2329066 TI - Objects to repeated reference to "harmful use of healthy animals". PMID- 2329067 TI - Directions in veterinary education. PMID- 2329068 TI - Taking a close look at toxocariasis. PMID- 2329069 TI - Bovine growth hormone raises national concern. PMID- 2329070 TI - Veterinarians should measure ethylene oxide sterilizing practices against health risks. PMID- 2329071 TI - Evidence from and about animals. PMID- 2329072 TI - ECG of the month. PMID- 2329073 TI - Medical dissolution of feline struvite urocystoliths. AB - The efficacy of a diet designed to facilitate dissolution of feline magnesium ammonium phosphate (struvite) uroliths was evaluated in 30 cases of urolithiasis, sterile struvite uroliths dissolved in a mean of 36 days after initiation of dietary treatment. In 5 cases of urolithiasis, struvite urocystoliths associated with urease-negative bacterial urinary tract infection dissolved in a mean of 23 days after initiation of dietary and antimicrobial treatment. In 3 cases of urolithiasis, struvite urocystoliths associated with urease-positive staphylococcal urinary tract infection dissolved in a mean of 79 days after initiation of dietary and antimicrobial treatment. Dissolution of uroliths in cats fed the treatment diet was associated with concomitant remission of dysuria, hematuria, and pyuria, and reduction in urine pH and struvite crystalluria. In one case, a urocystolith composed of 100% ammonium urate, and in another case, a urolith composed of 60% calcium phosphate, 20% calcium oxalate, and 20% magnesium ammonium phosphate did not dissolve. PMID- 2329074 TI - Persistence of antibodies to Borrelia burgdorferi in dogs of New York and Connecticut. AB - Multiple blood samples were obtained from privately owned dogs living in tick infested areas of New York (Westchester County) and Connecticut, where Lyme disease in human beings has been reported. Of the 175 dogs examined, 127 (72.6%) had limb/joint disorder, whereas the remaining 48 dogs were considered healthy. Results of analysis of 419 serum samples revealed IgM antibody to Borrelia burgdorferi in healthy and lame dogs during all seasons. Prevalence of seropositivity was significantly (P less than 0.01) greater, using a polyvalent ELISA (89.5%) than using a class-specific ELISA for IGM antibody (57.8%). Mean antibody titers obtained by use of polyvalent ELISA were likewise higher than IgM titers. Analysis of paired serum samples from dogs with limb/joint disorder indicated that 118 (92.9%) remained positive for IgM or IgG antibodies when retested weeks or months after initial testing. In 48 dogs without history of joint involvement or other signs of disease, 43 (89.6%) had antibody to B burgdorferi 2 or more times. Serotest results also revealed little or no change in antibody titer for lame dogs given antibiotics or for healthy dogs 2 or more months after initial sample collection. PMID- 2329075 TI - Efficacies of erythromycin and chloramphenicol in extinguishing fecal shedding of Campylobacter jejuni in dogs. AB - Oral treatment regimens of erythromycin stearate and chloramphenicol were evaluated in naturally infected laboratory colony dogs for their efficacies in extinguishing fecal shedding of Campylobacter jejuni. Of the 25 Campylobacter infected English Foxhounds in the study, 9 were assigned to erythromycin treatment, 9 to chloramphenicol treatment, and 7 to no treatment. Antimicrobials were administered for 12 days. All of the dogs that received erythromycin stearate ceased shedding C jejuni by the fourth day of treatment and remained negative throughout the treatment period. Chloramphenicol was associated with a reduction in shedding from 100% to 57% by the ninth day of treatment. Within 9 days of the discontinuation of antimicrobial treatment, C jejuni was isolated from all chloramphenicol-treated dogs and 89% erythromycin-treated dogs. PMID- 2329076 TI - Naltrexone for treatment of acral lick dermatitis in dogs. AB - Acral lick dermatitis (lick granuloma) was diagnosed in 11 dogs on the basis of history, physical examination, and histopathologic findings. A predilection for the left forelimb was noticed. All 11 dogs were given the narcotic antagonist naltrexone. Successful treatment (cessation of licking, reepithelialization of lesions) was seen in 7 dogs. All 7 dogs' lesions recurred when naltrexone was stopped, but reepithelialized in 5 dogs when the drug was readministered. Adverse effects (drowsiness, withdrawal from owner) were seen in 1 dog, but resolved within 48 hours of stopping the drug. PMID- 2329077 TI - Contracture test and histologic and histochemical analyses of muscle biopsy specimens from horses with exertional rhabdomyolysis. AB - Biopsy specimens of the cutaneous omobrachialis muscle were obtained from 10 horses with a problem of myositis from mild exercise. One horse had been evaluated previously and malignant hyperthermia-like contractures developed in its muscle biopsy specimen during the contracture test. In this study, the halothane-caffeine contracture test and histologic and histochemical evaluations were performed on muscle biopsy specimens. In the contracture test, no muscle biopsy specimen developed contracture in the presence of 2 or 4% halothane alone. The mean (+/- SEM) caffeine-specific concentration in the presence of halothane was 5.23 +/- 0.5 mM for 2% halothane, and 4.46 +/- 0.6 mM for 4% halothane. The caffeine-specific concentration values were not significantly different. Contracture response for any muscle specimen did not resemble contracture associated with malignant hyperthermia. The cutaneous omobrachialis muscle was composed of type-II fibers, with type-I fibers seldom seen. For 9 of the 10 horses, overall fiber morphology was normal; 1 horse had necrotic fibers. Of the 10 muscle specimens, 9 had fibers that had positive reaction for alkaline phosphatase activity; 3 muscle specimens contained ringed myofibers. Three horses of this study were administered general anesthesia; 2 were research horses, anesthetized with halothane and succinylcholine, and 1 was a clinical case given halothane anesthesia plus a non-depolarizing muscle relaxant. One research horse developed a malignant hyperthermia-like reaction to anesthesia, with severe rhabdomyolysis evident after anesthesia, and an episode of muscle cramping in its stall 2 days after anesthesia. The other 2 horses had unremarkable postanesthetic periods. PMID- 2329078 TI - Potential for the spread of Fasciola hepatica in cattle in Oklahoma. AB - In 29 central and western Oklahoma counties, 42 ranches were investigated for indigenous Fasciola hepatica infections and their suitability for the transmission of liver fluke. A 10-year retrospective study of Oklahoma cattle based on samples submitted to the Oklahoma Animal Disease Diagnostic Laboratory also was done. Indigenous fascioliasis was found in cattle in 12 counties (9 central and western counties identified in the combined field and retrospective studies and 3 additional eastern counties identified on the basis of the retrospective study). Factors essential for survival of free-living stages of F hepatica and for snail species necessary for propagation of the fluke existed in much of Oklahoma. Snails capable of serving as intermediate hosts for transmission of the fluke reportedly have been found in 41 of the 77 Oklahoma counties. Lymnaeid snails were detected in 4 counties in the field study. PMID- 2329079 TI - Mycoplasmal mastitis in a dairy herd. AB - In October 1985, mycoplasmas were isolated from bulk tank milk samples in a large Florida dairy (greater than 1,400 lactating cows). At that time, measures to isolate and control the spread of infection were instituted. In an initial screening test, Mycoplasma bovis was isolated from 21 of 153 milking string samples (milk from all quarters of 10 cows/string). Composite quarter milk samples from all quarters of every individual lactating cow in the herd were obtained for culture in November 1985 and December 1985. In October, 88 of 1,535 (5.7%) cows were identified as Mycoplasma-positive. An additional 31 Mycoplasma infected cows were identified in December. The dairy elected to maintain the infected cows in a separate Mycoplasma-positive subherd, which would be milked at the end of each milking session. Seven additional Mycoplasma-positive cows were identified at initiation of lactation. All newly identified infected cows were transferred to the Mycoplasma-positive subherd. After segregation of Mycoplasma positive cows, bulk tank milk samples obtained routinely from the main herd remained culture negative throughout the study. From February 1986 to October 1986, quarter milk samples were obtained monthly from cows in the Mycoplasma positive subherd. Any cow that developed clinical mastitis or substantial decrease in milk production was, at the discretion of the herdsman, culled. Of the 126 cows in the subherd, 22 (17.5%) were culled for mastitis, 35 (27.8%) were culled for low production, and 9 (7.1%) were culled for other reasons. Of the remaining 60 cows, 16 (12.7% of the 126 cows) were Mycoplasma-positive on the basis of results from one or more samples obtained after February 1986.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329080 TI - Seasonality of natural transmission of bovine anaplasmosis under desert mountain range conditions. AB - Splenectomized cattle and mature, spleen-intact cattle were used as sentinels in a 4-year study to assess the seasonality of naturally transmitted anaplasmosis. Sentinels were exchanged and/or monitored monthly on 4 study areas of desert mountain range land in Idaho, Oregon, and Utah. Acute Anaplasma infections were diagnosed in sentinels every month of the year. Of 44 total infections, 29 (66%) were detected during March through August, the primary arthropod season. From December through February, 8 (18%) of the total 44 Anaplasma infections were diagnosed; the winter tick, Dermacentor albipictus, was the probable disease vector. Susceptible cattle were determined to be at risk throughout the year, and anaplasmosis should be considered as a possible diagnosis in cattle with anemia during any season. PMID- 2329082 TI - Brucella ovis epizootic in virgin ram lambs. PMID- 2329081 TI - Methods for control of lamb epididymitis in large purebred flocks. AB - An autogenous, multivalent, adjuvanted bacterin for epididymitis was tested in flocks of 700 to 800 Suffolk X white-faced lambs. Long-term feeding of low dosages of antibiotics also was tested in the Suffolk flock. Both methods appeared to reduce the incidence of the disease. The incidence of clinical epididymitis and the number of positive culture results from clinically affected rams were significantly reduced. PMID- 2329083 TI - Halicephalobus (Micronema) deletrix infection in two half-sibling foals. PMID- 2329084 TI - Differentiation between intra-abdominal neoplasms and abscesses in horses, using clinical and laboratory data: 40 cases (1973-1988). AB - The medical records of 25 horses with intra-abdominal neoplasms and 15 horses with intra-abdominal abscesses were reviewed. Common clinical signs of disease observed by owners of horses in both groups included anorexia, weight loss, fever, signs of colic, and depression. Clinical laboratory abnormalities included leukocytosis, hyperfibrinogenemia, hypoalbuminemia, and hypocalcemia. There was considerable overlap of laboratory test results within and between the 2 groups of horses. Peritoneal fluid was classified as an exudate in 12 of 15 horses with intra-abdominal abscesses and in 14 of 25 horses with intra-abdominal neoplasms. Cytologic examination of peritoneal fluid yielded an accurate diagnosis in 11 of 25 horses with neoplasia and in 3 of 15 horses with abscesses. A mean number of 1.45 cytologic analyses/horse was needed to diagnose neoplasms in the 11 horses in which the analysis was successful in definitively diagnosing the condition. PMID- 2329085 TI - Partial rupture of the cranial cruciate ligament of the stifle in dogs: 25 cases (1982-1988). AB - Partial rupture of the cranial cruciate ligament was diagnosed in 25 dogs. In all dogs, the primary problem at the time of physical examination was hind limb lameness. The mean time from initial onset of lameness to diagnosis at exploratory surgery was 17 weeks. A cranial drawer sign was detected in 13 of the 25 dogs; in 9, the cranial drawer sign was evident only when the stifle was positioned in flexion. Of the 25 dogs, 12 had no detectable cranial drawer sign in response to manipulation of the involved stifle. In all dogs, lateral stifle arthrotomy was performed in routine manner, and the cranial cruciate ligament was found to be incompletely torn. Lesions identified during arthrotomy were rupture of the craniomedial band (n = 20 dogs), interstitial tear (n = 4 dogs), and rupture of the caudolateral band (n = 1 dog). PMID- 2329086 TI - Use of ivermectin for treatment of ear mite infestation in rabbits. AB - Ivermectin was used to treat ear mite infestation in 480 rabbits in 2 commercial rabbitries. Ivermectin (cattle formulation) injected sc at a dosage of 400 to 440 micrograms/kg of body weight repeated in 18 days appeared to be safe and effective in reducing the prevalence of ear mites in naturally infested rabbits. PMID- 2329087 TI - Lymphoproliferation in captive wild ruminants affected with malignant catarrhal fever: 25 cases (1977-1985). AB - The severity of lymphoproliferative disease associated with malignant catarrhal fever was extremely variable among 25 animals at the San Diego Wild Animal Park. Severe lymphoproliferative disease was seen in 3 of 10 Formosan Sika deer (Cervus nippon taiouanus), 3 of 6 Indian Axis deer (Cervus a axis), 3 of 6 Barasingha deer (Cervus d duvauceli), and 1 of 3 Nilgai (Boselaphus tragocamelus). Two Sika deer and 2 Barasingha deer had lesions morphologically indistinguishable from lymphosarcoma. Our findings were consistent with the hypothesis that alcelaphine herpesvirus-1 has oncogenic potential. PMID- 2329088 TI - What is your diagnosis? The navicular bone (distal sesamoid) is displaced proximally because of an avulsion fracture at the attachment of the impar ligament. PMID- 2329089 TI - Encoding of amplitude modulation in the gerbil cochlear nucleus: II. Possible neural mechanisms. AB - Rapid changes in sound amplitude--amplitude modulation (AM)--comprise an important feature of biologically-relevant sounds, including speech. In the companion paper, a hierarchy of enhancement for AM processing was demonstrated for unit types of the gerbil ventral cochlear nucleus (VCN) [Frisina, et al., Hear. Res. 44, 1990]. In the present report additional neurophysiological findings are presented as an initial test of alternative hypotheses of how VCN unit types amplify or enhance AM information, and how they accomplish this over a wide intensity range. These hypotheses invoke mechanisms such as off-CF excitatory or inhibitory inputs, input from high-threshold auditory-nerve fibers, amplification of residual AM responses of auditory-nerve fibers at high intensities, or post-synaptic cell feedback. From consideration of VCN unit response properties such as onset and steady-state rate-intensity functions, pure tone tuning, and non-CF responses to AM, it is concluded that: Off-CF excitatory inputs do not play a significant role in VCN AM encoding; Off-CF inhibitory inputs could work in conjunction with one or more of the other proposed mechanisms to account for differential enhancement of AM by VCN neurons. PMID- 2329090 TI - Changes in endocochlear potential during anoxia after intense noise exposure. AB - Endocochlear potentials (EPs) were investigated in healthy guinea pigs and in those exposed to white noise of 125 dB SPL for 20-80 min. EPs were measured during and after temporary anoxia (3.5 min, denoted as reversible anoxia) and then during continuous anoxia to evaluate noise-induced changes in EP properties. Succino-dehydrogenase (SDH) activity and morphologic changes in hair cells were also evaluated in surface preparations of the hair cells. It was found that changes in EPs correlated with the duration of noise exposure. The longer the noise exposure, the greater the decrease in EPs. EPs could recover in one week post-exposure, in roughly the same time needed for recovery of SDH activity in hair cells. Noise exposure also resulted in some changes in EP dynamic behaviour during and after reversible anoxia, but did not cause any significant change in maximal negative EP. The mechanisms underlying these results are discussed. PMID- 2329092 TI - Responses of single units in the anteroventral cochlear nucleus of the guinea pig. AB - Single unit responses have been recorded from the anteroventral cochlear nucleus of the anaesthetised guinea-pig. For each unit a response profile was obtained consisting of spike waveform shape, suprathreshold post-stimulus time histogram at characteristic frequency, frequency/intensity response area, a measure of phase-locking and where possible variation in post-stimulus time histogram shape as a function of position within the response area. Units were classified according to schemes based on both post-stimulus time histogram shape and response area. The majority of units with Type I response areas were primarylike and most with Type III response areas were choppers. One-to-one correspondence between the two classification schemes was found for units which were classified as onset by the post-stimulus time histogram scheme and Type I/III by the response area scheme. Primarylike units with a prepotential in their spike waveform most faithfully preserved the temporal information (as measured by phase locking) present in the auditory nerve input. Primarylike units in which a prepotential was not detected showed varying abilities to phase-lock. Non primarylike units do not phase-lock as well as auditory nerve fibres in the same species. Nonmonotonic rate-level functions for tones at characteristic frequency were observed across all unit types (with the exception of onset units) classified by the post-stimulus time histogram scheme. An unexpected finding was a small number of primarylike units characterised by reduced driven discharge rates within their response areas. We hypothesize that the mechanism for this reduction is centre-band inhibition. PMID- 2329091 TI - Evoked otoacoustic emissions in guinea pig: basic characteristics. AB - Different types of evoked otoacoustic emissions (EOAEs) such as stimulus frequency emissions, tone burst and click EOAEs, were investigated in the guinea pig. Their correlates on cochlear microphonic potential were also recorded. Although it was confirmed that click EOAEs are difficult to detect in the guinea pig, partly because their delay (2 to 3 ms, measured on tone burst EOAEs) is much shorter than in man, other types of OAE were found in the interval (1.5-5 kHz) for almost every normal animal. Many of their properties were quite different from man, for instance their small number, low level, and the wide frequency range of some of them (up to 500 Hz), suggesting that they represent a sort of continuum. It is proposed that these particularities may not arise from different generating mechanisms but should be correlated with the well-known differences in hair cells patterns. PMID- 2329093 TI - Apical hair cells and hearing. AB - This study assessed the contribution of the apical hair cells to hearing. Guinea pigs, chinchillas and monkeys were behaviorally trained using positive reinforcement to respond to pure-tone stimuli. When a stable audiogram had been determined, each subject received one of three experimental treatments: ototoxic drug administration, low-frequency noise exposure, or the application of a cryoprobe to the bony wall of the cochlear apex. After post-treatment audiograms stabilized, subjects were euthanized and the percentage of hair cells remaining was assessed by light microscopy. Results indicate that a redundancy of encoding mechanisms exist in the mammalian cochlea for low-frequency stimuli. They also suggest that a very small percentage of apical hair cells are sufficient for some low-frequency hearing. Finally, data from this and other studies suggest that the low-frequency threshold shift caused by the loss of a certain percentage of apical hair cells is less pronounced than the high-frequency threshold shift caused by the loss of a comparable percentage of basal hair cells. These data agree with anatomical and electrophysiological evidence that functional as well as anatomical differences may exist between the apex and base of the cochlea. PMID- 2329094 TI - Absence of tonic activity of the crossed olivocochlear bundle in determining compound action potential thresholds, amplitudes and masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities. AB - In Nembutal- or Urethane-anaesthetised guinea pigs N1 audiograms and N1 input output functions were measured as were compound action potential (CAP) tuning curves under forward masking and simultaneous masking conditions. Then the crossed olivocochlear bundle was lesioned at the floor of the fourth ventricle and the cochlear responses were re-measured. There were never any changes in the N1 audiograms, input-output functions, or the CAP tuning curves. Thus, the crossed efferent pathways do not appear to play any tonic role in determining cochlear threshold sensitivities, selectivities or masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities. PMID- 2329095 TI - Cochlear preprocessing in analog models, in digital models and in human inner ear. AB - Data of spontaneous, delayed, and simultaneously evoked otoacoustic emissions produced in human subjects are compared with data produced in an analog and in a digital wave-parameter realization of our model. The high probability of the frequency distance of the emission's extreme values at 0.4 Bark, corresponding to a local distance of 0.5 mm along the basilar membrane is found also in the models. The influence of the lateral feedback coupling in the models on the frequency selectivity and on the appearance of emissions show the high quality of simulating human peripheral signal processing by the models. PMID- 2329096 TI - Temperature effects on auditory nerve fiber response in the American bullfrog. AB - Single fiber recordings were made from auditory nerve fibers of the American bullfrog (Rana catesbeiana). As temperature was raised: (1) Best frequencies of fibers from the amphibian papilla (N = 15) increased. Below 600 Hz best frequency changes up to 0.06 oct/degrees C were found; above 600 Hz changes were less than 0.03 oct/degrees C. In the basilar papilla (N = 4) no significant increase of best frequency was found. (2) Spike rates in response to fixed-RMS-amplitude stimuli increased considerably: Q10 of spike rate ranged from 5 to 10. (3) Spontaneous activity, found in basilar papilla fibers, increased with average Q10 = 1.6 (+/- 0.3). (4) A conspicuous change of tuning quality factor Q10 dB was only observed in two fibers, that were taken to low temperatures (less than 16 degrees C). (5) the nearly linear frequency vs. phase relation in amphibian papilla shifts to higher frequency (along with shift of best frequency), while its average slope remains nearly unchanged. PMID- 2329097 TI - Saturation of outer hair cell receptor currents causes two-tone suppression. AB - Zwicker [Biol. Cybern. 35, 243-250, (1979); J. Acoust. Soc. Am. 80, 163-176 (1986)] has previously proposed that many nonlinear phenomena in the mammalian cochlea can be explained by saturation of a positive feedback process which enhances mechanical sensitivity, although the site of the nonlinearity producing this saturation has so far remained obscure. In this paper we present evidence suggesting that the nonlinearity of mechano-electrical transduction in the outer hair cells is the dominant nonlinearity producing two-tone suppression in the mammalian cochlea. In particular, we show that: (i) suppression of the extracellular summating potential (SP), recorded from a particular place within the organ of Corti, has characteristics similar to the suppression of activity in the auditory-nerve; (ii) that SP suppression occurs at approximately constant basilar membrane displacement, inferred from the SP iso-response contours; and that (iii) the onset of SP suppression with suppressor tones on the tail of the frequency tuning curve closely parallels the onset of nonlinearity in the local cochlear microphonic. Since previous studies (Patuzzi et al., 1989) have demonstrated that the vibration of the basilar membrane at its characteristic frequency is very sensitive to changes in outer hair cell receptor current, we consider that interference in outer hair cell currents caused by nonlinearity in mechano-electrical transduction is an adequate explanation of two-tone suppression. This requires that outer hair cell receptor currents deviate from linearity at a suppressor tone level below that required to produce a significant DC receptor potential within the inner hair cells, and that the active process within the cochlea is distributed along a local region of the cochlea, basal of the vibration peak. PMID- 2329098 TI - Encoding of amplitude modulation in the gerbil cochlear nucleus: I. A hierarchy of enhancement. AB - The main goal of the present study was to investigate the encoding of a biologically-relevant acoustic feature--amplitude modulation (AM)--in single neurons of the auditory nerve and ventral cochlear nucleus (VCN). In the anesthetized gerbil auditory-nerve fibers and VCN units show strong synchronous responses to low-intensity, low-frequency AM. As frequency increases, the strength of the synchronous response decreases. In the auditory nerve the strength of the synchronous response is substantially less at high intensities than at low intensities and does not change significantly with AM frequency at high intensities. In contrast to the auditory nerve, VCN units show strong responses at high intensities. They have a particular AM frequency to which they are maximally responsive, and this frequency varies from unit to unit. Therefore, VCN units transform their ascending inputs by enhancing the synchronous response to AM. A correlation exists between a unit's ability to encode AM and its responses to simple sounds. Specifically, onset units show the strongest synchronous responses, followed in order by chopper, primarylike-with-notch and primarylike units. This enhancement is greatest at high intensities and can occur up to 90 dB above a unit's threshold. Thus, a hierarchy of enhancement for AM processing exists in the most peripheral nucleus of the central auditory system. PMID- 2329099 TI - Comparison of four methods for the determination of MIC and MBC of penicillin for viridans streptococci and the implications for penicillin tolerance. AB - Four methods of MIC and MBC determination were examined to compare their reproducibility and ability to detect penicillin tolerance. The MIC and MBC of penicillin were determined for 28 strains of viridans streptococci by a microdilution method, a macrodilution method, a membrane method, and a gradient plate method using a spiral-plating device. The macrodilution, membrane and gradient plate methods were found to be acceptable for MIC determination with a reproducibility to within one doubling dilution, but only the gradient method gave acceptable reproducibility for MBC determinations. The consequence of these findings with respect to penicillin tolerance is discussed. PMID- 2329100 TI - The in-vitro activity of ceftibuten against 475 clinical isolates of gram negative bacilli, compared with cefuroxime and cefadroxil. AB - The in-vitro activity of ceftibuten was compared with cefuroxime and cefadroxil against 475 clinically-significant, epidemiologically-distinct isolates of Gram negative bacilli: 170 from blood, 212 from urine and 93 from a supplementary collection of multiply-resistant strains known to have resistance plasmids, to have caused sporadic or epidemic nosocomial infection, or both. Ceftibuten MICs ranged from 0.003 to greater than 32 mg/l, with a modal MIC of 0.01 mg/l: 95% of all isolates had ceftibuten MIC values of less than or equal to 8 mg/l, the sensitivity breakpoint suggested by the manufacturer. Ninety per cent of isolates had MICs of less than or equal to 1 mg/l and 49% had MICs of less than or equal to 0.03 mg/l. All isolates of Klebsiella, Serratia, Proteus and Providencia spp., and Morganella morganii had MIC values of 8 mg/l or less. Only two of 124 isolates of Escherichia coli tested, and only one of 23 Citrobacter spp., had MICs of greater than 8 mg/l (16, 16 and greater than 32 mg/l respectively). Resistance MIC greater than 16 mg/l) was more frequent among Enterobacter and Acinetobacter spp. Thirteen of 52 Enterobacter spp., and seven of 18 Acinetobacter calcoaceticus had MICs of at least 32 mg/l. MIC ranges, modal MICs and MIC90s indicated that ceftibuten was, with the exception of only two strains, consistently more active in-vitro than cefuroxime, which was in turn more active than cefadroxil. PMID- 2329101 TI - In-vitro activity of SCH39304 in comparison with amphotericin B and fluconazole. AB - The in-vitro activity of SCH39304, a new imidazole, was compared with that of amphotericin B using two media (Sabouraud dextrose and tissue culture (TC) medium) with or without 25% human serum. At an inoculum of 1.5 X 10(4) cfu/ml, the IC95% for amphotericin B ranged from 0.08 to 0.3 mg/l irrespective of the medium. At the same inoculum, the IC95% of the two imidazoles ranged from 0.3 to greater than 80 mg/l. The inoculum effect (from 1.5 X 10(4) to 1.5 X 10(5) cfu/ml) was less than 1 dilution for the three antifungal agents. Serum increased the inhibitory activity (IC80%) of SCH39304 and fluconazole but not of amphotericin B. The IC80%, IC95% and minimal fungicidal concentration (MFC) for amphotericin B usually ranged within two dilutions. Using kill curve methodology, the initial killing rate (0-4 h) of amphotericin B correlated with concentration (P less than 0.001), and was faster in TC medium than in Sabouraud dextrose (P less than 0.0006). SCH39304 and fluconazole did not produce any significant killing over the range of concentrations tested (0.5-20 mg/l). SCH39304 was similar to fluconazole. PMID- 2329102 TI - The effect of pentamidine salts on the NADPH-dependent oxidase of stimulated neutrophilic granulocytes. AB - Both pentamidine isethionate and pentamidine mesylate induced a depression in activity of the NADPH-dependent oxidase system of stimulated human neutrophilic granulocytes. This drug-induced effect occurred at concentrations of 0.7, 1.1 and 1.5 mg/l, values within the therapeutic range after parenteral administration of a standard dose of either pentamidine salt, and was dose-related. There was no significant difference between the two salts with regard to this suppression in neutrophilic granulocyte function. The reduced activity of the NADPH-dependent oxidase system, after incubation with pentamidine salts, may be associated with the previously observed depression in candidacidal capacity of human neutrophilic granulocytes treated with these drugs. PMID- 2329103 TI - The apparent absorption kinetics of Ro 15-5458, a schistosomicidal drug. AB - The absorption kinetics of Ro 15-5458, a new antischistosomal drug, was studied in rabbits following the administration of a single 50 mg/kg oral dose as an aqueous suspension in 25% glycerol-1% cremophor EL. Ro 15-5458 was absorbed from the gastrointestinal tract rapidly with a lag time of about 6 min and declined without a plateau with a half-life of about 6 h. There was variable extent of drug appearance in plasma after oral administration. Maximum plasma levels ranged from 500 to 1200 ng/ml (1.3-3.1 microM). The plasma concentration-time profile of Ro 15-5458 after a single oral dose appears to follow a one-compartment pharmacokinetic model with zero-order absorption, first-order elimination. PMID- 2329104 TI - Pharmacokinetics of intravenous amoxycillin and potassium clavulanate in seriously ill children. AB - The pharmacokinetics of amoxycillin and potassium clavulanate were studied in 15 sick children after a 30 min iv infusion of 50 mg/kg amoxycillin and 5 mg/kg clavulanic acid as the potassium salt. Levels of both compounds in plasma were assayed microbiologically. Mean peak concentrations at the end of the infusion were 121.0 mg/l of amoxycillin and 12.0 mg/l of clavulanate, falling to a mean of 15.8 and 1.92 mg/l respectively after 2 h. Mean beta phase T 1/2 was 0.88 h for amoxycillin and 0.79 h for clavulanate. The elimination half-life of clavulanate in some individuals was much shorter because of higher plasma clearance. The data suggest that the treatment of some infections due to beta-lactamase producing organisms in such severely ill children may require more frequent iv administration of amoxycillin and potassium clavulanate, than in less severely affected children. PMID- 2329105 TI - Chemoprophylaxis of bacterial endocarditis--a survey of current practice in Zimbabwe. AB - There is no information about the use of antibiotics in the prevention of bacterial endocarditis in a developing country. A questionnaire was posted to 73 dentists, 233 general practitioners and 43 physicians. Completed questionnaires were received from 31 (42%) dentists, 59 (25%) general practitioners and 15 (35%) physicians. Prophylactic practice differed from the current published recommendations in the choice of drugs, dosage regimens, and a longer duration of use before and after invasive procedures. Wider dissemination of authoritative recommendations would simplify current practice. PMID- 2329106 TI - Ciprofloxacin in combined renal and hepatic impairment. PMID- 2329107 TI - The successful treatment of multiresistant nonenteric salmonellosis with seven day oral ciprofloxacin. PMID- 2329108 TI - Neurotoxicity of acyclovir in end stage renal disease. PMID- 2329109 TI - Inactivation of amoxycillin, clavulanate and the combination by faecal preparations from volunteers. PMID- 2329110 TI - Development of ciprofloxacin resistance in Brucella melitensis. PMID- 2329111 TI - A fractographic analysis of in vivo poly(methyl methacrylate) bone cement failure mechanisms. AB - Cementing with poly(methyl methacrylate) (PMMA) is a common means of fixing total hip prostheses. Bone cement fails mechanically, and subsequent loosening frequently requires correction via revision surgery. An initial step in optimizing bone cement properties is to establish which properties are critical to the material's in vivo performance. The objectives were to discern the critical in vivo failure mechanisms of bone cement. Fracture surfaces of bone cement specimens that failed in vivo were compared with fatigue and rapid fracture surfaces created in vitro. In vivo fracture processes of bone cement were positively identified and explained by the elucidation of PMMA fracture micromechanisms. The ex vivo fracture surfaces are remarkably similar to in vitro fatigue fracture surfaces. The fractographic data document that the primary in vivo failure mechanism of bone cement is fatigue, and the fatigue cracks grow by developing a microcraze shower damage zone. Agglomerates of BaSO4 particles can be implicated in some bone cement failures, large flaws or voids in vivo can lead to a rapid, unstable fracture, pores in the PMMA mass have a clear influence on a propagating crack, and wear of the fracture surfaces occurs, and may produce PMMA debris, exacerbating bone destruction. PMID- 2329112 TI - Surface passivation by human albumin of plasmapheresis circuits reduces platelet accumulation and thrombus formation. Experimental and clinical studies. AB - The contact of flowing blood with an artificial surface leads to adsorption of plasma proteins, followed by platelet adhesion and aggregation and thrombus formation. This phenomenon is enhanced by turbulent flow at joints, bifurcations, and constrictions. In therapeutic plasmapheresis using an IBM blood cell separator, blockage of the extracorporeal circulation system by platelet-fibrin thrombi imposed a halt in treatment for manual clearance of the circuit for 66 in 149 cases (44%). Thus it was decided to passivate the surface of the extracorporeal circuit by filling the tubing with 4% human serum albumin 15-20 min before the treatment session and then displacing the albumin solution with the patient's blood without creating an air-liquid interface. After introduction of this technique, a blockage was observed for only 11 in 239 cases (5%). In vitro measurements of platelet accumulation on the internal surface of the circulation system were carried out using washed human platelets labeled with 111In-oxine in the presence of a 40% hematocrit. Preadsorption of the surface with albumin reduced platelet deposition to 4-5% that observed for an equivalent pretreatment with physiological saline. PMID- 2329113 TI - The influence of calcium phosphate biomaterials on human bone cell activities. An in vitro approach. AB - An in vitro method is described to assess the influence of synthetic calcium phosphate powders on osteoblast activities. Human osteoblast cell cultures were established from iliac crest. MC3T3-E1, an established osteogenic cell line, was employed as a control. Scanning and transmission electron microscopic observations clearly demonstrated the internalization of particles of calcium phosphate by the two osteoblast cell populations. As a consequence to the phagocytotic process, RNA transcription and protein synthesis were stimulated, as indicated by the measurements of labeled uridine, leucine and proline uptakes. From these data, it is proposed that such an in vitro model, using one of the specific cell types involved in the tissue responses to implants, could be useful to assess the biological response at the cell-biomaterial interaction. PMID- 2329114 TI - Cyclic fatigue-crack propagation, stress-corrosion, and fracture-toughness behavior in pyrolytic carbon-coated graphite for prosthetic heart valve applications. AB - Fracture-mechanics tests were performed to characterize the cyclic fatigue, stress-corrosion cracking, and fracture-toughness behavior of a pyrolytic carbon coated graphite composite material used in the manufacture of cardiac valve prostheses. Testing was carried out using compact tension C(T) samples containing "atomically" sharp precracks, both in room-temperature air and principally in a simulated physiological environment of 37 degrees C Ringer's lactate solution. Under sustained (monotonic) loads, the composite exhibited resistance-curve behavior, with a fracture toughness (KIc) between 1.1 and 1.9 MPa square root of m, and subcritical stress-corrosion crack velocities (da/dt) which were a function of the stress intensity K raised to the 74th power (over the range approximately 10(-9) to over 10(-5) m/s). More importantly, contrary to common perception, under cyclic loading conditions the composite was found to display true (cyclic) fatigue failure in both environments; fatigue-crack growth rates (da/dN) were seen to be a function of the 19th power of the stress-intensity range delta K (over the range approximately 10(-11) to over 10(-8) m/cycle). As subcritical crack velocities under cyclic loading were found to be many orders of magnitude faster than those measured under equivalent monotonic loads and to occur at typically 45% lower stress-intensity levels, cyclic fatigue in pyrolytic carbon-coated graphite is reasoned to be a vital consideration in the design and life-prediction procedures of prosthetic devices manufactured from this material. PMID- 2329115 TI - In vitro biocompatibility of polyetheretherketone and polysulfone composites. AB - Short carbon fiber reinforced composites could potentially replace some of the metal alloys used in orthopedic implants. In particular, polysulfone and, more recently, polyetheretherketone have been considered as the matrix material for carbon fiber reinforced composite implant materials. ASTM standards F813 and F619 for direct contact cell culture evaluation and extraction were employed to determine the in vitro biocompatibility of a carbon fiber composite of polyetheretherketone, PEEK, in comparison to a carbon fiber reinforced polysulfone composite. The cell cultures were assessed qualitatively by microscopy and quantitatively using an enzyme assay to determine cytotoxicity. Overall, the cellular response to the PEEK and polysulfone composites were negligible indicating that further in vivo studies with these materials are appropriate. PMID- 2329116 TI - A new porous polyetherurethane wound covering. AB - A polyetherurethane (PEU) wound covering with non-interconnected micropores up to approximately 5 microns has been prepared by means of a phase inversion process. This highly elastic, very thin (15-20 microns), pliable wound covering showed good, immediate adherence to wet wound surfaces and high water vapor permeability, but was impermeable to bacteria. In guinea pigs epidermal wound healing of partial-thickness wounds under PEU wound coverings was accelerated compared with uncovered controls and an occlusive wound covering, OpSite. Water in liquid form or wound exudate could not leak through the PEU covering, but its high water vapor permeability induced concentration of the wound exudate into a jellylike clot layer, which apparently accelerated reepithelialization. The main conclusion from a clinical study on 20 donor sites was that the use of the PEU covering reduced pain, besides prevention of fluid retention. No differences in epithelialization were seen in comparison to tulle gras-treated wounds. PMID- 2329117 TI - Adsorption of plasma proteins and adhesion of platelets onto novel polyetherurethaneureas--relationship between denaturation of adsorbed proteins and platelet adhesion. AB - Novel polyetherurethaneureas which have been synthesized by the present authors were chosen for the substrate polymers, on which adhesion of platelets was investigated. The number of adhered platelets and the amount of serotonin released from platelets adhered on the polymers and the protein-coated polymers were determined by radioisotope method. Both of them were enhanced with increasing content of urea linkages in the polyetherurethaneureas. The platelet adhesion was discussed in terms of the denaturation of plasma proteins upon adsorption, which was determined by Fourier-transform infrared spectroscopy. With increasing degree of protein denaturation, the platelet adhesion and the serotonin release were enhanced. This relationship was particularly evident in the case of albumin adsorption. It was shown that the surface properties of substrate polymers affect the protein adsorption, which in turn influences the adhesion of platelets. PMID- 2329118 TI - Preparation of spherical encapsulation of activated carbons and their adsorption capacity of typical uremic toxins. AB - A method has been designed for making spherical microencapsulation of activated carbon particles for use in the removal of metabolic wastes and/or toxins from blood. This bench-scale method was able to make better uniformity in particle size, and at a higher particle production rate. The material properties such as particle size, particle porosity, electromicroscopy of surface morphology, surface hardness, and pore-size distribution were characterized in order to conclude with their adsorption capacity for specific toxin solutes. The performance characteristics of these self-prepared particle encapsulation was also evaluated against the commercially available hemoperfusion particles, e.g., Kuraray's DHP (Japan). The encapsulation particles were also coated with polyhydroxyethyl methacrylate (PHEMA) for blood compatibility purpose. PMID- 2329119 TI - A two-compartment description and kinetic procedure for measuring regional cerebral [11C]nomifensine uptake using positron emission tomography. AB - S-[11C]Nomifensine (S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood--brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a "free" NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its "binding potential" to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers. PMID- 2329120 TI - Reduction of functional capillary density in human brain after stroke. AB - The blood flow of brain tissue often returns to normal after an ischemic episode. As "luxury" rather than "reactive" reperfusion, this hyperemia is associated with low metabolism. It is not known to what extent the high blood flow accompanies a high, normal, or low density of capillaries. The resolution of this question may indicate whether the functional capillary density is variable and, if so, whether it is coupled to blood flow or metabolism. To answer these questions, we defined functional capillaries as capillaries that transport glucose. We then calculated the density of functional capillaries (Dcap) and the mean time of transit of blood through the capillaries (tcap) from hemodynamic variables obtained in vivo by positron tomography of five patients afflicted by cerebral ischemic stroke. Each patient was studied twice, within 36 h of the insult and 1 week later. We identified nominally "ischemic" regions in the first study as cortical gray matter regions, contiguous with the ischemic focus, in which the magnitude of blood flow did not exceed 20 ml 100 g-1 min-1. In these regions, values of metabolism and functional capillary density were proportionately low compared with normal values obtained in the contralateral hemisphere. The studies revealed a reduction of the functional density of exchange vessels in postischemic brain tissue as soon as 36 h after the insult. In "ischemic" regions, within 36 h of the insult, the net extraction of oxygen was inversely related to the capillary transit time and appeared to be limited mainly by the low functional density of the capillaries. Contrary to expectations, the reduced density persisted, even when more than adequate perfusion of the tissue returned. For these reasons, we concluded that changes of the capillary density were associated with changes of the metabolism of the tissue rather than with blood flow. PMID- 2329121 TI - Autoregulation of cerebral blood flow in experimental focal brain ischemia. AB - The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood-flow (CBF) in areas of focal cerebral ischemia was studied in 15 spontaneously hypertensive rats (SHRs) anesthetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flowmetry during manipulation of SAP with I-norepinephrine (hypertension) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipulations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of greater than 30% of preocclusion values. In areas where ischemic CBF was less than 30% of preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was less than 15% of baseline (6% change in CBF with each 10% change in SAP). These findings demonstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the severity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia. PMID- 2329122 TI - Eicosanoids in rat brain during ischemia and reperfusion--correlation to DC depolarization. AB - The effects of complete ischemia on cerebral arachidonic acid (AA) metabolism were investigated in the isolated perfused rat brain. During 12.5 min of ischemia, AA, 5-hydroxy-6,8,11,14-eicosatetraenoic acid, and 15-hydroxy-5,8,11,13 eicosatetraenoic acid increased 129-, 4-, and 10-fold, respectively, while subsequent reperfusion for 30 min resulted in normalized levels independently of the duration of preceding ischemia. Prostaglandin (PG) F2 alpha, PGE2, PGD2, 6 keto-PGF1 alpha, and thromboxane (Tx) B2 remained at preischemic levels during 12.5 min of complete ischemia. However, at the end of subsequent reperfusion for 30 min, the levels of the prostanoids PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha, and TxB2 increased according to the preceding ischemic time. The levels reached a maximum after 7.5 min of ischemia and were elevated by 7-, 14-, 48-, 3-, and 30 fold, respectively. A prolongation of ischemia of up to 12.5 min was not associated with further increases of prostanoids at the end of reperfusion. The mechanisms underlying the metabolism of eicosanoids are discussed in relation to the changes of cortical direct current potential. PMID- 2329123 TI - The influence of mild body and brain hypothermia on ischemic brain damage. AB - The influence of brain and body temperature on ischemic brain damage, notably on the density and distribution of selective neuronal vulnerability, was studied in SPF-Wistar rats subjected to 15 min of forebrain ischemia induced by bilateral occlusion of the common carotid arteries combined with arterial hypotension (50 mm Hg) in a room air environment. In one group of animals, the body temperature was maintained at 37 degrees C but no attempt was made to prevent heat losses from the ischemic brain; i.e., the head was not heated during ischemia. Under those conditions the temperature of the caudoputamen and at a subcutaneous site over the skull bone spontaneously fell to approximately 32 degrees C. In four other groups, both the rectal and the subcutaneous skull temperatures were maintained at 38, 37, 35, and 33 degrees C during the ischemia. Our results confirm those recently reported when brain temperature was varied during 20 min of ischemia, with body temperature kept constant. Thus, the histopathological outcome of the brain damage, as assessed after 7 days of recovery, was strongly temperature dependent. Whereas ischemia at 37-38 degrees C consistently caused neuronal necrosis in the hippocampus, neocortex, and caudoputamen, spontaneous cooling of the brain during ischemia at a rectal temperature of 37 degrees C significantly reduced the ischemic damage. Intentional lowering of temperature to 35 degrees C markedly reduced and to 33 degrees C virtually prevented neuronal necrosis in some but not all of the regions studied. While damage to the caudoputamen was extremely temperature sensitive, that affecting the CA1 sector of the hippocampus, and particularly the lateral reticular nucleus of the thalamus, was less so. Our results suggest that whatever biochemical events are responsible for selective neuronal vulnerability, they are temperature sensitive; however, since there are differences in sensitivity between different parts of the brain, more than one mechanism may be involved. PMID- 2329124 TI - Dissociation by chloralose of the cardiovascular and cerebrovascular responses evoked from the cerebellar fastigial nucleus. AB - We studied the effects of chloralose anesthesia on the elevation in arterial pressure (AP), heart rate (HR), and regional CBF (rCBF) elicited by stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized with an initial dose of chloralose (40 mg/kg s.c.), paralyzed, and artificially ventilated. The FN was stimulated (50-100 microA, 50 Hz, 1 s on/1 s off) with microelectrodes stereotaxically implanted. During the stimulation AP was carefully maintained within cerebrovascular autoregulation. CBF was measured by the [14C]iodoantipyrine technique with regional dissection. In rats that received only the initial dose of chloralose, FN stimulation elevated rCBF in brain and spinal cord, up to 209 +/- 13% of control in frontal cortex (n = 5; p less than 0.01, analysis of variance). Administration of additional chloralose (10 mg/kg i.v., 30 min prior to measurement of CBF) did not affect resting rCBF (n = 5), the EEG, or the elevation in AP and HR elicited by FN stimulation (n = 4). However, the additional chloralose abolished the elevations in rCBF (n = 5; p greater than 0.05). Thus, the cerebrovasodilation elicited from the FN is more susceptible to the effects of additional anesthesia than the elevation in AP and HR. These results indicate that the cerebrovascular and cardiovascular responses elicited from the FN are functionally distinct and provide additional evidence for the notion that these responses are mediated by different neural pathways and transmitters. PMID- 2329125 TI - Selective electrical stimulation of postganglionic cerebrovascular parasympathetic nerve fibers originating from the sphenopalatine ganglion enhances cortical blood flow in the rat. AB - Recently, the origins and pathways of cerebrovascular acetylcholine- and vasoactive intestinal polypeptide-containing nerves have been elucidated in detail in the rat: The sphenopalatine ganglion is the major source for postganglionic parasympathetic fibers to the vascular beds of the cerebral hemispheres. To clarify the functional role of the nerves on cerebral blood vessels in vivo, brain cortical microvascular blood flow was measured in rats during electrical stimulation of these particular postganglionic fibers. Animals were subjected to transection of the right nasociliary nerve 2 weeks before the flow measurements to eliminate activation of peptidergic sensory fibers. Relative change in microvascular blood flow was continuously recorded by a laser-Doppler flowmeter system under alpha-chloralose anesthesia. The postganglionic fibers were electrically stimulated just proximal to the ethmoidal foramen by a bipolar platinum electrode (5 V; 0.5 ms; 3, 10, 30, 60 Hz; as a continuous stimulation for 90 s). Stimulation at 10 Hz induced a marked increase of the cortical blood flow (CoBF) on the ipsilateral side, whereas no change was observed on the contralateral side. It reached a maximum mean value of 42.5% at 46 s, and then slightly declined during the remaining stimulation period. No significant changes were observed in the mean arterial blood pressure or blood gases during or after stimulation. Both atropine and scopolamine failed to alter this flow increase. Electrical stimulation of the postganglionic fibers at different frequencies revealed a maximal increase in the CoBF at 30 Hz in the control situation (47.2%), but at 10 Hz after scopolamine administration (51.6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329126 TI - Effect of adenosine on total and regional cerebral blood flow of the newborn piglet. AB - The effect of adenosine on total and regional CBF, measured by radiolabeled microspheres, was assessed in 16 anesthetized and ventilated newborn (1-3 days old) piglets. They received a ventriculocisternal perfusion containing either CSF alone (controls, n = 5) or CSF mixed with two different concentrations of adenosine (15 min each) randomly assigned using the following doses: 0.1 microM, 10 microM, 100 microM, 1 mM (n = 4), or 10 mM (n = 6). Mean CSF adenosine concentration (by HPLC) before perfusion was 0.6 +/- 0.4 microM. Total and regional CBF were not altered by the perfusion of CSF alone. All adenosine concentrations, except at low doses, increased total and regional CBF, without altering the cerebral metabolic rate for oxygen. Brainstem blood flow was increased by a mean of 110, 145, 306, and 378% with 10 microM, 100 microM, 1 mM, and 10 mM concentrations, respectively. Except for the highest concentration, CBF response was dose dependent in each region of the brain with the following order of potency: brainstem greater than periventricular area greater than telencephalon, midbrain, total brain, and cerebellum. These data indicate that, in the newborn, adenosine is a potent vasodilator of cerebral vessels. If the newborn brain can synthesize appropriate concentrations of adenosine, this nucleoside may play a major role in regional CBF regulation during the neonatal period. PMID- 2329127 TI - Origins and pathways of choline acetyltransferase-positive parasympathetic nerve fibers to cerebral vessels in rat. AB - The presence of cholinergic nerve fibers in the brain vasculature has been a matter of controversy, partly due to the lack of a reliable histochemical marker. Accordingly, no distinct information about the origin and pathways for such fibers has been available. In the present study on the rat pial vasculature, utilizing a choline acetyltransferase (ChAT) antibody, which is able to demonstrate this enzyme in peripheral nervous tissue, evidence was obtained for an innervation by cholinergic fibers of large pial arteries. Vasoactive intestinal polypeptide (VIP) was present in or in close association with these fibers. By the aid of the retrograde axonal tracer True Blue (TB) applied to the middle cerebral arterial wall, such fibers were shown to originate in a subgroup of ChAT-positive cells in the sphenopalatine, otic, and internal carotid ganglia, which, in addition, contained VIP. The ChAT-positive pial nerve fibers were few in relation to the VIP-immunoreactive fibers, as was also illustrated by the few TB-positive cells in the ganglia that were ChAT positive as compared with the number of cells that were VIP positive. Only a small population of ChAT containing neurons in these ganglia appeared to project to the pial vessels. The pathway from the sphenopalatine ganglion is via a membranous structure on the medial orbital wall, through the ethmoidal foramen, and along the internal ethmoidal artery to reach the circle of Willis. The fibers from the internal carotid and otic ganglia probably bridge to the internal carotid artery in the carotid canal, those from the otic ganglion after an initial course in the lesser superficial petrosal nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329128 TI - Effect of dipyridamole on cerebral extracellular adenosine level in vivo. AB - The effect of dipyridamole, an adenosine transport inhibitor, on cerebral extracellular adenosine concentration remains to be determined. To examine this issue, bilateral brain dialysis samples were obtained from piglet frontal cortex before, during, and after 5 min of cerebral ischemia; 10(-4) M dipyridamole was administered through one dialysis probe. On the control side, dialysate adenosine concentration increased 5.7-fold during ischemia and 15-fold during the first 5 min of reperfusion; it returned to control levels after 15 min of reperfusion. Relative to the control side, dipyridamole caused a twofold increase in basal dialysate adenosine concentration and increased dialysate adenosine concentration at 10 and 15 min of reperfusion, but no increase in dialysate adenosine occurred during and immediately after ischemia. The results indicate that, in the piglet brain, cerebral ischemia markedly elevates intracerebral extracellular adenosine concentration and that dipyridamole increases extracellular adenosine levels. PMID- 2329129 TI - Actions of platelet-activating factor on isolated feline and human cerebral arteries. AB - The effects of platelet-activating factor (PAF) were studied on isolated feline basilar arteries (BAs) and human pial arteries (PAs). PAF contracted the BAs by 67% of the contraction induced by 124 mM K+ and the PAs by 80%. The contraction in BAs was unaffected by both indomethacin and the thromboxane receptor antagonist AH23848. PAF relaxed prostaglandin F2 alpha-contracted arteries. In BAs 10(-6) M PAF reduced the contraction by 17% and in PAs by 47%. The relaxant effects in both arteries were unaffected by indomethacin. In conclusion, PAF can act both as a constrictor and as a dilator of isolated feline and human cerebral arteries. The effects are seemingly unrelated to vascular prostanoid production. PMID- 2329130 TI - The difference in vascular volume between cerebrum and cerebellum is in the pia mater. AB - Previous studies using intravascular tracers have shown that the apparent vascular volume in the cerebellum is 10-60% higher than that in the cerebrum. We questioned whether the extravascular volume in the cerebellum could be accounted for by the vasculature of the pia mater that covers its highly infolded surface. Estimates of vascular volume were made using a previously reported point-counting method. Two counts were done: one in which only intraparenchymal vessels were included, and a second one in which both intraparenchymal vessels and pial vessels were included. We found no differences in intraparenchymal vascular volume between cerebellum and cerebrum. When the pial vessels are included, however, the cerebral vascular volume increases by less than 6%, whereas the cerebellar vascular volume increases by greater than 30%. We suggest that the higher cerebellar vascular volume measured using intravascular tracers is due to inclusion of the pial vasculature. Since pial vessels do not express blood-brain barrier characteristics as prominently as intraparenchymal vessels, we further suggest that estimates of barrier permeability in cerebellum should not be made using simple models developed for cerebral tissue. PMID- 2329131 TI - Refinement of the kinetic model of the deoxyglucose method. PMID- 2329132 TI - The metabolic centroid method for PET brain image analysis. PMID- 2329133 TI - Nursing care of clients in transition. PMID- 2329134 TI - Transitions in professional identity of nurses enrolled in graduate educational programs. PMID- 2329135 TI - Third trimester concerns of expectant parents in transition to parenthood. PMID- 2329136 TI - Developmental transitions in adulthood: mother-daughter relationships. PMID- 2329137 TI - The mother-daughter relationship during daughter's first pregnancy: the transition experience. PMID- 2329139 TI - Transition in adolescence and its potential relationship to bulimic eating and weight control patterns in women. PMID- 2329138 TI - The transition of relocation to a nursing home. PMID- 2329140 TI - The near-death experience as a major life transition. PMID- 2329141 TI - Method for radio-capillary gas chromatography employing a modified oxidation reduction train and flow-through detector. AB - A conventional radioactivity monitor was modified by reducing the volume of the oxidation-reduction train and gas proportional counting tube to permit coupled radio-capillary gas chromatographic analysis of labeled isomeric metabolites. The utility of this radioactivity monitoring technique was demonstrated by separating 3H-labeled sesquiterpene olefins. The advantages and limitations of mass (thermal conductivity) and radioactivity detection by this method are discussed. PMID- 2329142 TI - Selection of electrophoric derivatives of 1-aminopyrene and 2-aminofluorene for determination by gas chromatography with electron-capture negative-ion mass spectrometry. AB - Several electrophoric derivatives of 1-aminopyrene and 2-aminofluorene were prepared. Reagents such as heptafluorobutyryl chloride, pentafluorobenzoyl chloride, pentafluorobenzyl bromide and pentafluorobenzaldehyde, alone and in certain combinations, were employed. The ease of formation, yield, stability and fragmentation by gas chromatography with electron-capture negative-ion (ECNI) mass spectrometry of the derivatives were compared. This allowed the most promising ones to be selected for future work on the sensitive detection of aminopolyaromatics by this detection technique. Pentafluorobenzylidene (first choice) and N-pentafluorobenzyl-N-heptafluorobutyryl (second choice) derivatives emerged as the best ones. The origins of losses of HF and 2HF from some of the derivatives were elucidated in the ECNI mass spectra by studies of deuterium labeled analogues. PMID- 2329143 TI - Opioid and tachykinin peptides, and their precursors and precursor-processing enzymes, in human cerebrospinal fluid. AB - Opioid and tachykinin neuropeptides, which were derived from two biological sources (intact, and released from their corresponding precursors by the action of human cerebrospinal fluid (CSF) neuropeptidases), were characterized in human CSF by using a combination of post-high-performance liquid chromatographic (HPLC) detection techniques. Peptides were separated using gradient and isocratic reversed-phase HPLC. Radioimmunoassay measured immunoreactivity corresponding to several different individual neuropeptides including methionine enkephalin, leucine enkephalin, substance P and beta-endorphin. Commercial enzymes (trypsin, carboxypeptidase B) were used to release methionine- and leucine-enkephalin from precursors. Human CSF also served as a source of endogenous neuropeptidases. Mass spectrometry produced fragment ions that corroborated the amino acid sequence of methionine enkephalin and of substance P derived from both sources (intact, from precursors). These results demonstrated the presence of endogenous intact neuropeptides, several different neuropeptide-containing precursors and appropriate precursor-processing enzymes in human CSF for precursors of methionine enkephalin, leucine enkephalin, beta-endorphin1-31 and substance P. PMID- 2329144 TI - Separation and quantification by gas chromatography-mass spectrometry of arabinitol enantiomers to aid the differential diagnosis of disseminated candidiasis. AB - To differentiate increased arabinitol due to fungal (only D-arabinitol) and non fungal origin, O-trifluoroacetyl derivatives of the enantiomers were separated using alpha-perpentylated cyclodextrin columns and measured by selected ion monitoring. Mean +/- S.D. D/L in normal serum: 1.40 +/- 0.42. D/L ratios greater than 2.24, defined as normal mean + 2S.D., were considered outside normal range. D/L was greater than 2.2 in 10 of 12 confirmed candidiasis cases with one false negative and one borderline. Renal dysfunction without candidiasis yielded normal D/L despite high arabinitol concentrations. D/L in normal urine was nearly identical to that in serum despite 60 times larger concentration. D/L ratios, determined by peak heights or areas, could be used without the need to determine concentrations. PMID- 2329145 TI - Gas-liquid chromatographic profiling of plasma lipids using high-temperature polarizable capillary columns. AB - We have examined the potential usefulness in plasma lipid profiling of capillary columns coated with a high-temperature-polarizable phenylmethyl silicone liquid phase, previously employed for gas-liquid chromatography (GLC) of natural triacylglycerols. The column yielded an excellent resolution for plasma triacylglycerols, cholesteryl esters and the trimethylsilyl (TMS) and tert butyldimethylsilyl (t-BDMS) ethers of free cholesterol, as well as of the TMS and t-BDMS ethers of the diacylglycerols and ceramides released from plasma phospholipids by phospholipase C digestion. The various lipid classes were resolved into molecular species according to chain length and number of double bonds. The different molecular species were recovered in variable proportions as indicated by comparisons of peak area percentages obtained on the polar columns with those recorded on non-polar columns, which have been previously shown to give correct quantitative proportions. The cholesteryl esters are thermally degraded at high temperatures and must be eluted at as low a temperature as possible. Under the selected experimental conditions, the cholesteryl esters were found to partly interdigitate with the triacylglycerol species of carbon numbers 46-48. The TMS and t-BDMS ethers of diacylglycerols and ceramides emerged clearly ahead of the leading triacylglycerol of the 42 acyl carbon series. However, the diacylglycerol and ceramide species overlapped and interdigitated extensively with each other. Due to low polarity below 280 degrees C, the polarizable-liquid phase was not suitable for the resolution of the molecular species of monoacylglycerols and free fatty acids, which were separated on the basis of carbon number only. Nevertheless, capillary GLC on the polarizable liquid phases provides a novel and informative profiling of plasma lipids, the application of which to the assay of plasma lipid abnormalities deserves further examination. PMID- 2329146 TI - Automated high-performance liquid chromatographic determination of plasma free fatty acids using on-line derivatization with 9-bromomethylacridine based on micellar phase-transfer catalysis. AB - The on-line use of micellar phase-transfer catalysis is described for the automated reversed-phase high-performance liquid chromatographic (RP-HPLC) determination of free fatty acids in plasma; minimum manual sample handling is involved. After diluting plasma ten-fold with the aqueous micellar system, which contains 25 mM of the non-ionic surfactant, Arkopal N-130 and 6 mM of the ion pair agent tetrakis(decyl)ammonium bromide, the reaction of the fatty acids with the fluorophore 9-bromomethylacridine is complete within 5 min at 60 degrees C. Prior to RP-HPLC separation, interfering proteins are removed using an on-line filter and a column-switching unit. More than 100 samples can be injected onto a single pre-column. The detection limit is ca. 300 nM; the precision is better than 3% using an internal standard. PMID- 2329147 TI - On-line combination of dialysis and column-switching liquid chromatography as a fully automated sample preparation technique for biological samples. Determination of nitrofuran residues in edible products. AB - The potential of dialysis coupled on-line with trace enrichment by column switching high-performance liquid chromatography as an automated sample treatment technique in drug residue analysis has been investigated. The nitrofuran veterinary drugs furazolidone, nitrofurazone, nitrofurantoin and furaltadone were used as model compounds. Critical parameters, i.e., dialyser dimensions, air segmentation, dialysis time, flow-rates and enrichment column breakthrough, were evaluated. Depending on the analytical purpose, the technique can be set up in either a highly sensitive or a high-speed mode. High dialysis efficiencies (greater than 85%) can be obtained in a stopped-flow dialysis of only 3 min. Aqueous biological sample volumes (eggs, meat, milk) of 100 microliters to 4 ml can be injected with only sample treatment. A routine monitoring method for residues of nitrofuran drugs in edible products was set up. A 4-ml sample was dialysed in a pulsed mode with an efficiency of about 30% and concentrated on a short C18 column. Recoveries compared with standards were 75-85% (coefficient of variation 2-7%). Limits of determination ranged from 1 to 10 micrograms/kg. At this concentration level, ca. 30 samples can be monitored per day. PMID- 2329148 TI - Intrinsic fluorescence studies of the kinetic mechanism of unfolding of alpha lactalbumin on weakly hydrophobic chromatographic surfaces. AB - The kinetic mechanism of unfolding of calcium depleted bovine alpha-lactalbumin adsorbed on two weakly hydrophobic chromatographic surfaces, methyl- and ethyl polyether phases bonded to porous silica, with a solution phase of 3 M ammonium sulfate at pH 6.3, has been determined using intrinsic fluorescence and liquid chromatography (LC). The adsorbent has been packed into quartz flow cells which are used for both fluorescence measurements and as a microcolumn for LC. The LC measurements revealed two peaks for alpha-lactalbumin on both phases, the first being folded and the second unfolded. The rate of unfolding was measured to be 1.75.10(-3) min-1 on the Cl-ether and 7.42.10(-3) min-1 on the C2-ether phase. Fluorescence studies revealed a slow change in emission maximum from ca. 330 nm to 350 nm and a 4-fold increase in intensity for the protein adsorbed on the two supports. Variation of fluorescence intensity at a given wavelength revealed biphasic kinetics in which the rate law on the surface was deduced as F in equilibrium X----U, where F is the folded form, U an unfolded form and X an intermediate. The normalized emission spectra of the three species were calculated and it was found that there was approximately a 20-nm-red shift in the position of the maximum from F to U. The emission maximum for X was close to U on both columns; however, the normalized intensity for X was between F and U. Activation enthalpies and entropies were determined from the temperature dependence of the microscopic rate constants. The formation of the intermediate on the C1-ether phase was entropy driven whereas on the C2-ether phase it was enthalpy driven. Finally, the solution refolding rates of U desorbed from the two supports were found to be identical. The differences observed in the surface kinetics of unfolding on the two supports are related to the hydrophobic differences of the adsorbents. PMID- 2329149 TI - Differential interaction of peptides and protein surface structures with free metal ions and surface-immobilized metal ions. AB - We have examined the influence of free metal ions on the affinity of structurally defined proteins and peptides for model surface-immobilized metal ions. The model proteins chosen differed widely in both the type and quantity of surface accessible electron donor groups. Metal ion affinity chromatography and equilibrium binding analyses demonstrated that the presence of excess free Cu(II) ions did not measurably affect either the affinity or the binding capacity of lysozyme for immobilized iminodiacetate-Cu(II). Similarly, the presence of excess free Cu(II) ions did not detectably affect the chromatographic behavior or measured affinity of either copper-saturated lactoferrin or iron-saturated lactoferrin for the immobilized Cu(II) ions. Its binding capacity however, was diminished. The affinities of small peptides for immobilized Cu(II) ions was found to be related to their number of His residues. Peptides with 0, 1, 2 and 3 His residues were resolved by high-performance immobilized Cu(II) affinity chromatography in both the presence and absence of added Cu(II) ions. In the presence of excess free Cu(II) ions, however, retention (affinities) of these peptides by immobilized Cu(II) ions was increased in relation to their number of His residues. These data demonstrate that protein surface binding sites for free and immobilized metal ions are functionally distinct. The presence of free and/or protein surface-bound metal ions does not preclude interaction with the same immobilized metal ions. Stationary phase immobilized metal ions can be a useful model system through which we can better understand the influence of macromolecular surface-immobilized metal ions on macromolecular recognition events. The significance of these findings are also important to the design of other site-specific and domain-specific affinity reagents involving metal ions. PMID- 2329150 TI - High-performance liquid chromatography of proteins on deformed non-porous agarose beads. Fast boronate affinity chromatography of haemoglobin at neutral pH. AB - Aminophenylboronic acid was attached to epoxy-activated non-porous agarose beads with diameters of 12-15 microns and this boronate gel column was used for the fractionation of glycosylated from non-glycosylated haemoglobin. By varying the experimental conditions it was shown that the ratio between the second peak (glycosylated haemoglobin) and the first peak (non-glycosylated haemoglobin) was virtually independent of pH in the range 7-8, ionic strength, flow-rate and sample load (up to at least 160 microliters of haemolysate on a 0.7-ml column). It is therefore not necessary to control thoroughly these parameters in order to obtain reproducible results, which is a great advantage in fast routine analyses of glycosylated haemoglobin. At a flow-rate of 4.0 ml/min an analysis was finished within 2 min on a 2.5 cm x 0.6 cm I.D. column. The total time of an analysis was also short because a sample from a droplet of blood could be applied directly onto the column after haemolysis for 1 min without removal of cell debris by time-consuming centrifugation. The experiments were performed at a pH close to the isoelectric point of haemoglobin, because at this pH haemoglobin has a negligible net charge and will therefore not interact with the charged groups of the ligands, the matrix and proteins adsorbed in previous runs. PMID- 2329151 TI - Carbohydrates as a tool for oriented immobilization of antigens and antibodies. AB - A biospecific sorbent for the isolation of ovalbumin antibodies was prepared by coupling of ovalbumin via its periodate-oxidized carbohydrate moiety to bead cellulose modified with adipic acid dihydrazide. The anti-ovalbumin IgG fraction isolated on this sorbent from immune rabbit serum contained only antibodies against protein determinants of ovalbumin. Thus, when these IgG were immobilized through their carbohydrate moieties to cellulose beads it became possible to prepare a biospecific sorbent for concanavalin A by oriented adsorption of ovalbumin. Ovalbumin was specifically adsorbed via its protein moiety and its carbohydrate part remained free for interaction with concanavalin A. PMID- 2329152 TI - Application of high-performance hydrophobic-interaction chromatography to the characterization of recombinant DNA-derived human growth hormone. AB - This publication analyzes different preparations of recombinant human growth hormone (rhGH) by hydrophobic-interaction chromatography (HIC). The effect of temperature on the separation was investigated as well as a series of commercially available HIC columns (TSK-phenyl-5PW, TSK-ether-PW, Beckman CAA-HIC and polypropyl A). The TSK-ether column gave the best results in the analysis of rhGH samples at different temperatures, as well as allowing an efficient separation of methionyl-hGH from rhGH. The TSK-phenyl column can be effectively used in the examination of different human growth hormone variants. The details of sample preparation have been demonstrated to be important in HIC analysis of hGH on the TSK-ether-5PW column. Injection volume and the solvent used to dissolve the protein sample are both crucial factors in this analysis. Also protein aggregation may play a role in these observations. The effect of temperature, protein concentration and spectroscopic data on the eluted protein suggest, however, that aggregation is not the cause of frontal peaks. PMID- 2329154 TI - Enantioselective determination of metoprolol in plasma by liquid chromatography on a silica-bonded alpha 1-acid glycoprotein column. AB - The enantiomers of metoprolol were determined in plasma samples after direct resolution on a silica bonded alpha 1-acid glycoprotein column. Metoprolol was extracted from plasma into a diethyl ether-dichloromethane mixture and after back extraction to dilute phosphoric acid and adjustment of pH the sample was injected on a Chiral-AGP column for separation of R- and S-metoprolol. It was possible to measure down to 2 nmol per litre plasma with a relative standard deviation of less than 15% by use of gradient elution and fluorescence detection. The analytical method was employed to study the pharmacokinetics of the metoprolol enantiomers after administration of the racemate to humans. PMID- 2329153 TI - Hippuric acid and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid in serum and urine. Analytical approaches and clinical relevance in kidney diseases. AB - Hippuric acid (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (FA) were determined in serum, plasma, ultrafiltrate and urine by gas chromatography (GC), high-performance liquid chromatography and GC with mass-selective detection, and the methods were compared. As determined by affinity chromatography and analysis of serum and ultrafiltrate, 0.5% of FA in serum occurs free and 99.5% is bound to albumin. In haemodialysed patients with chronic renal failure, the plasma levels of HA and FA are elevated in comparison with normal controls and hospital patients without kidney diseases: HA, 11.1 +/- 5.7 mg/dl (n = 86); FA, 1.9 +/- 1.2 mg/dl (n = 86). Gradual increases in HA in serum, depending on the creatinine concentrations, are found in non-dialysed patients with chronic renal failure. By haemodialysis and haemofiltration the HA levels are lowered (53-66 and 30-36%, respectively), whereas FA is not dialysable. PMID- 2329155 TI - Evaluation of photometric high-performance liquid chromatographic data for the determination of benflurone metabolites in biological materials with and without concomitant use of a standard. AB - The results produced by a new method of calculation based on the knowledge of the absorption coefficient and instrumental parameters without the concomitant use of a standard were compared with those calculated by the routine external standard method for a model system utilizing the quantification of benzofluorene derivatives. These were present in the incubation mixture of 5-[2 (dimethylamino)ethoxy]-7-oxo-7H-benzo[c]fluorene (benflurone) with the microsomal fraction of rat liver homogenate. Reasonable agreement between the two methods was observed. The potential utility of the new method of calculation is discussed. PMID- 2329156 TI - Determination of trichloroethanol, the active metabolite of chloral hydrate, in plasma by liquid chromatography. PMID- 2329157 TI - Preparative purification of human monoclonal antibody isoforms in a multi compartment electrolyser with immobiline membranes. AB - The performance of a multi-compartment electrolyser with isoelectric Immobiline membranes for large-scale protein purification is evaluated. Owing to the presence of isoelectric membranes possessing a high buffering capacity and ionic strength, isoelectric protein precipitation inside the membranes, one of the major drawbacks of present membrane uses, is fully avoided. In addition, owing to this novel membrane technology, pH gradient decay, typical of isoelectric focusing in carrier ampholytes, is fully eliminated and pH and conductivity constancy is guaranteed in all flow chambers for running periods of more than 11 days (160,000 V h). The membranes described possess a unique selectivity, in that they act by modulating the surface charge (i.e., the mobility) of macroions crossing or tangential to them. The concept of isoelectric Immobiline membranes acting like a pH-stat unit is introduced. Protein homogeneity in each chamber of the electrolyser can be achieved even when purifying human monoclonal antibodies against HIV-1, which possess high pI values (9.0-9.6), are large molecules (Mr 150,000) and are fractionated in the presence of large micelles of neutral detergents. PMID- 2329158 TI - Simultaneous determination of creatine, uric acid and creatinine by high performance liquid chromatography with direct serum injection and multi wavelength detection. AB - An isocratic high-performance liquid chromatographic separation of creatine, uric acid and creatinine with direct on-column application of the serum sample has been developed. The pre-column, used for sample clean-up, is switched out of the eluent flow after a definite time. Simultaneous three-wavelength detection with a diode array detector allows a very precise quantitation of the three compounds at the optimum wavelength for each (210, 234 and 290 nm) with a coefficient of variation of less than 2% (creatine 3-5%). Good linearity and 100% recovery are obtained over a wide range of concentration in biological material. No interferences are observed caused by medication with lidocaine or dobesilate (Ca), or high bilirubin concentrations. This makes the method useful for clinical purposes or even as a reference for other methods. PMID- 2329159 TI - Determination of creatinine-related urinary uracil excretion in children by high performance liquid chromatography. AB - Excretion rates of uracil and thymine in children (n = 140) and circadian rhythms of urinary uracil excretion (n = 9) were investigated by reversed-phase high performance liquid chromatography with ultraviolet detection. Excretion values were related to urinary creatinine determined by Jaffe's method. Creatinine related uracil excretion was not dependent on age or sex. The values seemed to be distributed according to a Gaussian graph in both school children and those in hospital. The intra-individual range was 1.32-23.70 mg uracil per g creatinine over a four-day period in one subject. Uracil excretion seems to be somewhat lower during the night. PMID- 2329160 TI - Determination of L-thyroxine in reference serum preparations as the o phthalaldehyde-N-acetylcysteine derivative by reversed-phase liquid chromatography with electrochemical detection. AB - A simple procedure for the assay of L-thyroxine in serum preparations with D thyroxine as internal standard is described. The L-thyroxine is extracted with acetonitrile, fractionated on a reversed-phase silica cartridge and analysed by reversed-phase high-performance liquid chromatography of the o-phthalaldehyde-N acetyl-L-cysteine derivative. This derivative is not fluorescent, but may be detected with suitable sensitivity and selectivity with an electrochemical detector. PMID- 2329161 TI - Purification of urokinase by combined cation exchanger and affinity chromatographic cartridges. AB - Crude urokinase from human urine processed through foam flotation and ammonium sulfate precipitation containing 720 National Health Institute Committee on Thrombolytic Agents U/mg activity was purified by an SP cation exchanger followed by a zinc-chelated affinity chromatographic cartridge. The cartridges were of a radial-flow type formed by using acrylic and cellulose composite matrices. The high rigidity of the matrix structure permits fast flow of protein solutions (liters per minute) and thus allows processing of a large volume of crude urokinase under low operating pressures. A greater than six-fold increase in specific enzyme activity of urokinase was achieved by adsorbing and eluting 1 l of a 3 mg/ml crude urokinase solution on an SP cartridge. The eluent was further purified by passing through a zinc-chelated affinity cartridge to achieve greater than a eighteen-fold increase in urokinase specific activity. This report demonstrates the combined use of a cation exchanger with zinc-chelated chromatographic cartridges in purifying urokinase on a relatively large scale. The relationship between the amount of zinc chelated in the matrix to its effect on urokinase purification is also discussed. PMID- 2329162 TI - Analysis of human tear proteins by different high-performance liquid chromatographic techniques. AB - A comparison of the efficiencies of hydrophobic interaction chromatography, ion exchange chromatography, reversed-phase chromatography and gel permeation chromatography in the separation of tear proteins was made using a variety of different buffers. Separation of immunoglobulins, lactoferrin, albumin, PMFA (protein migrating faster than albumin) and lysozyme was accomplished by gel permeation chromatography in less than 30 min using a TSK-type SW3000 column equilibrated with ammonium acetate buffer (pH 4.1) with a high reproducibility. When gel permeation chromatography was used as a completely automated diagnostic method, only minute volumes (1.0 microliter) of tear samples were necessary for the quantitative analysis of proteins. The other three methods proved to be more suitable for the preparation of individual tear proteins but were less suitable for their quantitation. PMID- 2329163 TI - Determination of nornicotine in smokers' urine by gas chromatography following reductive alkylation to N'-propylnornicotine. AB - A sensitive gas chromatographic assay has been developed to measure concentrations of nornicotine in human urine. A structural analogue, 5 methylnornicotine, is used as an internal standard. Both nornicotine and the internal standard were converted to the corresponding N'-propyl derivatives using a novel reductive alkylation procedure. The N'-propyl derivatives have good chromatographic properties, which allows quantitative measurement in the low nanograms per milliliter range. Concentrations of nornicotine in smokers' urine were quantitated and compared with the concentrations of nicotine and its metabolites, cotinine, nicotine-N-oxide and cotinine-N-oxide. PMID- 2329164 TI - Sensitive high-performance liquid chromatographic assay for the determination of eugenol in body fluids. AB - The high-performance liquid chromatographic assay described permitted a simple, rapid, sensitive, selective and precise quantitative determination of eugenol in body fluids (serum, urine and bile) without derivatization. Amounts in the range 0.02-100 micrograms of eugenol per millilitre of body fluid were determined with intra-assay coefficients of variation below 4% (3.72-1.13%). The short analysis time for each sample and the selectivity even at low concentrations made this assay suitable for pharmacokinetic studies. Eugenol undergoes a pronounced first pass effect; in serum, unconjugated eugenol was not detected after an oral dose of 150 mg. The kinetics of eugenol conjugates were measured. More than 80% of the dose was excreted within 6 h after oral administration. PMID- 2329165 TI - Fast reliable assay for morphine and its metabolites using high-performance liquid chromatography and native fluorescence detection. AB - A method for the fast analysis of morphine (M), normorphine (NM), morphine-3- and -6-glucuronides (M3G and M6G) and codeine (C) is described which has the advantages of sensitivity, speed and specificity. Dihydrocodeine and heroin can also be assayed. The method is based on extraction of the opiates from serum, plasma and cerebrospinal fluid using reversed-phase solid-phase extraction columns, followed by reversed-phase high-performance liquid chromatography with native fluorescence detection. The extraction step provides greater than 95% recovery, and the response of the detection system is linear from 0.5 to beyond 750 ng. The method allows analysis of M, NM, M3G, M6G and C. No other drugs have been found to interfere with the assay. The assay offers a quick, cheap and reliable method of specifically determining morphine and its metabolites, including the potent M6G, from a small sample volume; this will be of advantage to both clinician and basic scientist. PMID- 2329166 TI - High-performance liquid chromatographic assay of iomeprol in plasma and urine. AB - A high-performance liquid chromatographic method for assaying the radiographic contrast agent iomeprol in plasma and urine samples is described. Before reversed phase chromatography, the biological fluids are treated with ion-exchange resins and iopamidol is added as internal standard. The compounds are monitored during elution by ultraviolet-visible spectrometry at 245 nm. The method shows good precision and accuracy and gives similar results to X-ray fluorescence analysis. PMID- 2329167 TI - Determination of the antimitotic agents N-desacetylcolchicine, demecolcine and colchicine in serum and urine. AB - In an effort to characterize the pharmacokinetic behavior of the antimitotic agent N-desacetylcolchicine a selective, sensitive high-performance liquid chromatographic method was developed for the determination of N desacetylcolchicine, demecolcine and colchicine in serum or urine. To 0.5 ml of serum or 0.1 ml of urine diluted to 0.5 ml were added 50 microliters demecolcine (2 micrograms/ml) which serves as the internal standard. The sample was extracted using a C2 reversed-phase solid extraction column. N-Desacetyl-colchicine, colchicine and the internal standard were eluted from the column with methanol. The combined eluates were evaporated to dryness and the residue was reconstituted with water. The reconstituted sample was injected into a C18 reversed-phase column and eluted using a mobile phase consisting of 0.1 M potassium dihydrogenphosphate, 5 mM 1-pentanesulfonic acid in methanol and acetonitrile with a final pH of 6.0, at a flow rate of 1.5 ml/min. N-Desacetylcolchicine, colchicine and the internal standard were detected using a variable-wavelength ultraviolet detector at 254 nm. The limit of detection was 0.4 ng/ml for desacetylcolchicine and 4.0 ng/ml for colchicine. The method is linear over a concentration range of 1.0-200 ng/ml. The method has been shown to be a rapid, reliable method to monitor N-desacetylcolchicine levels in clinical trials in cancer patients. PMID- 2329168 TI - Automated gel permeation chromatography of plasma lipoproteins by preparative fast protein liquid chromatography. PMID- 2329169 TI - Isolation of human lactoferrin by affinity chromatography using insolubilized bovine beta-lactoglobulin. PMID- 2329170 TI - Determination of isosorbide-5-mononitrate in human serum by gas chromatography mass spectrometry. PMID- 2329171 TI - Rapid monitoring of chloramphenicol in microsamples of plasma by capillary gas chromatography with electron-capture detection. PMID- 2329172 TI - Determination of a cytostatic agent, bendamustine, in plasma using capillary gas chromatography with nitrogen-selective detection. PMID- 2329173 TI - Short-column liquid chromatographic assay for caffeine and chloramphenicol in serum. PMID- 2329174 TI - High-performance liquid chromatographic determination in human plasma of a new immunomodulatory agent with a peptidyl-hypoxanthine structure (RM 06). PMID- 2329175 TI - High-performance liquid chromatographic assay for cefotiam and d3-cefotiam in human serum. PMID- 2329176 TI - High-performance liquid chromatographic assay of rifampicin in human serum. PMID- 2329177 TI - [Clinical and pathological evaluation of periodic synchronous discharge observed in advanced dementia of Alzheimer type]. AB - Among 78 carefully diagnosed dementia of Alzheimer type (DAT) patients, periodic synchronous discharges (PSD) on electroencephalograms (EEGs) were observed in 12 advanced cases. Although several case studies have been made since 1970, it is not widely recognized that PSD can be observed in advanced DAT patients. In this study the clinical picture, the nature of PSD, background activity of EEGs and 2 autopsied cases have been clinicopathologically investigated. The mean duration of the disease in the 12 cases was 6.7 years. The mean age of onset of the disease was 67 years of age. Among the 12 cases, 9 patients presented akinetic mutism or symptoms closely resembling akinetic mutism, who were completely bed ridden with their extremities fixed in flexion. The other 3 patients were severely demented. They presented various degrees of Parkinsonian syndromes or paratonic rigidity accompanied by some infection and general fatigue. In one of these 3 patients, PSD were observed during the transient apallic state and the PSD themselves were also transient. The basic rhythm in EEGs were 4-6 c/s: middle amplitude theta waves dominant with delta waves on frontal leads. Triphasic delta, theta and sharp waves of PSD were dominant on centro-parieto-occipital leads. Background activity was not suppressed differing from that of Creutzfeld Jacob disease (CJD). According to the interval histograms of PSD, the majority presented an interval of 1-2 s (1.5 s mean) with some lability which was relatively slower than that of CJD. Fronto-parieto-occipital delay was not observed. By 1 c/s photic stimulation, PSD was not driven.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329178 TI - [The relation between myc family gene abnormality in lung cancers and xenotransplantability]. AB - Thirty-four primary lung cancers were analyzed for abnormalities in the myc family genes (c-myc, N-myc, L-myc), using the Southern blot hybridization method. They were subcutaneously transplanted into nude mice. The Southern blot analysis showed that c-myc and L-myc genes were amplified in 4 non-small cell carcinomas and 3 small cell carcinomas respectively. Allelic deletion of the L-myc gene was observed in 7 cancers, including 2 carcinomas which also had an additional band of the c-myc gene or amplification of the L-myc gene. No abnormalities in the N myc gene were observed in this study. Of 13 cancers with abnormalities in the myc family genes, 11 including all tumors with myc gene amplification were transplantable to nude mice. Of 21 tumors without any abnormalities in the myc family genes, however, only 6 were transplantable to nude mice (p less than 0.005). These results indicate that abnormalities in the myc family genes, especially gene amplification might promote tumor-forming capacity in xenotransplantation of lung cancers and this phenomenon might be closely related to the function of the myc gene. PMID- 2329179 TI - [Histological and immunohistochemical studies on nevocellular nevi in the dermis. With special reference to the histogenesis of nevus cells]. AB - The author has performed study on the histogenesis of the nevus cells in the nevocellular nevi. In the study, specimens of the intradermal nevi in 124 cases were evaluated histologically and immunohistochemically and the following results were obtained: 1) Findings of hematoxylin eosin staining It was observed that three types of cells, including type A cells (epidermoid type cells), type B cells (lymphoid type cells), type C cells (neuroid type cells) were found to run through an intermediate stage from the upper part to the lower part of the nevocellular structure, although they disclosed different histological structures. In 39 (31.5%) of the 124 cases, Meissner's corpuscle-like cells were confirmed. 2) Findings of immunohistochemical staining i. Of the type A, type B and type C cells, the S-100 alpha protein stain was essentially negative. Meissner's corpuscle-like cells were selectively positive by this stain. ii. Although no particular difference was noted in the staining of S-100 protein between the type A and type B cells, a somewhat greater proportion of positive cells was noted in type C cells. In the Meissner's corpuscle-like cells, a notably higher positive conversion of cells was observed as compared to those of the three other types of cells. iii. Type A, type B and type C cells compared more or less similarly for the positive ratio of neuron-specific enolase but the ratio was unusually high in the Meissner's corpuscle-like cells. 3) Findings from routine electron microscopic staining i. Similar to the light microscopic findings, the nevus cells were found to change in shape uninterruptedly from the upper layer to the lower layer of the dermis. Unusually marked changes were noted both in the number and shape of the melanosome and premelanosome in the cytoplasm. ii. In the Meissner's corpuscle-like cells both melanosomes and premelanosomes were missing but a finding suggestive of a neuroid structure was affirmed. As noted above, the results of the histological, immunohistological and electron microscopic studies were in support of the general findings suggestive of a gradual shift of the nevus cells from the upper layer to the lower layer in the dermis, which prompted the author to support the so-called "neural crest origin hypothesis". PMID- 2329180 TI - [Responses of plasma eicosanoids and hemodynamics to myocardial ischemia and the salutary effect of calcium entry blocker]. AB - The responses of eicosanoids to acute myocardial ischemia induced by either exercise stress testing (EX) or percutaneous transluminal coronary angioplasty (PTCA) were investigated in 23 patients with effort angina pectoris (EAP). EX was useful procedure to determine the therapeutic plan in each cases, and PTCA is the novel therapeutic operation for EAP. The relations between these metabolites and either hemodynamics or coronary circulation were then evaluated. The effect of the calcium entry blocker nisoldipine (oral administration of 5 mg) was also studied in 10 patients with EAP. The plasma levels of thromboxane B2 (TXB2), 6 keto-prostaglandin F1 alpha (6KPGF1 alpha) and leukotriene C4 (LTC4) were determined by radioimmunoassay. in arterial and coronary sinus blood samples before and immediately after acute myocardial ischemia. The changes in hemodynamics and coronary circulation during exercise stress testing were assessed by measuring direct brachial artery pressure, cardiac output by the dye dilution method and coronary sinus flow by the thermodilution method. The TXB2/6KPGF1 alpha ratio in coronary sinus blood significantly increased after ischemia in both EX and PTCA, but there was no significant change in LTC4 levels of coronary sinus blood immediately after acute ischemia. The 6KPGF1 alpha levels in both arterial and coronary venous blood were significantly correlated to coronary perfusion pressure and mean brachial artery pressure. Arterial LTC4 levels tended to correlate to mean brachial artery pressure and coronary sinus flow. Nisoldipine improved the ischemic electrocardiography response to EX. Nisoldipine also significantly increased arterial 6KPGF1 alpha at peak exercise. It significantly decreased brachial artery pressure, pressure rate product (PRP), mean coronary sinus pressure and coronary vascular resistance both at rest and peak exercise. The response of PRP significantly correlated with the response of arterial 6KPGF1 alpha. These results suggest: 1 The imbalance of the TXB2/6KPGF1 alpha ratio may be induced more rapidly than LTC4. 2 PGI2 and LTC4 may have some role in the regulation of hemodynamics and coronary circulation during acute myocardial ischemia. 3 Nisoldipine may ameliorate myocardial ischemia through improvement of systemic hemodynamics and prostaglandin metabolism apart from through direct action on the heart. PMID- 2329181 TI - [An ultrastructural investigation of changes in hypoxia in the subependymal layer of the newborn rabbit]. AB - Fetal and neonatal hypoxia is suggested as a noticeable risk factor related to the occurrence of subependymal hemorrhages. To investigate the cause of newborn subependymal hemorrhages, a 0 day old newborn rabbit was exposed to either 5 or 10 minutes hypoxia by N2 box. After exposure, the brain was observed by optical and electric microscope using horseradish peroxidase (HRP) as the protein tracer to study the change in the capillary permeability. The result obtained were as follows: 1) In the newborn rabbit blood gas analysis, PO2 (mmHg) decreased more in the 5 and 10 min hypoxia groups than the control group which used the N2 box. pH and BE changes were similar to PO2 (mmHg). On the other hand, PCO2 (mmHg) increased proportionately. These results indicated that this hypoxic method changed blood gas and caused acidosis. 2) In the optical microscopic examination, the 0 day old newborn rabbit brain was found to have a thin subependymal layer. We could not find obvious subependymal hemorrhage using optical microscope. 3) In the electric microscopic examination, HRP was found in the cavity of the brain capillary at the subependymal layer and was slightly incorporated into the pinocytic vesicle of the lumen on the control. Since the tight junction filled the roll out, HRP was not found outside the capillary. 4) The 5 min hypoxia group caused astrocyte foot swelling, edema and slight opening of the tight opening of the tight junction. HRP was passed through the tight junction, but not outside the capillary. 5) The 10 min hypoxia group caused destruction of astrocyte and edema around the capillary. The tight junction was more opened than in the 5 min hypoxia group and HRP leaked out of the capillary through the tight junction. From the findings mentioned above, it is suggested that our hypoxic model increased permeability of the capillary in subependymal layers and that this change might be the first ultrastructural change before the onset of subependymal hemorrhages. PMID- 2329182 TI - [Peridurograms in patients with lumbar disc herniations]. AB - The epidural space lies between the dural tube and the inside wall of the spinal canal. It contains fibrous tissues which adhere snugly to both walls filling the dead space between them. In the space, there are a large number of venous vessels anteriorly, a little fat tissue posteriorly and nerve roots laterally. The space can be examined clinically by a peridurographic technique in which the epidural space is filled with an iodine contrast medium. In patients with lumbar intervertebral disc herniation (IDH), this examination is useful to determine the location of the prolapsed nucleus pulposus and the pathological adherent condition by the filling defect of contrast medium. For the purpose of determining the pathology of the prolapsed nucleus pulposus, peridurographic examinations were performed on 40 patients with IDH and the following results were obtained: 1) The existence and location of the IDH were shown by the peridurograms. 2) Adhesion around the involved and uninvolved nerve roots was shown in proportion to clinical symptoms. PMID- 2329183 TI - [Efficacy of percutaneous transluminal coronary angioscopy]. PMID- 2329184 TI - [Clinical use of magnetic resonance imaging]. PMID- 2329185 TI - Rett syndrome: a longitudinal developmental case report. AB - Rett syndrome is a recently described progressive neurological disorder of unknown etiology occurring only in females, causing severe to profound mental retardation and characterized by loss of purposeful hand use and stereotypic hand movements. The present study examined development in five areas: gross motor skills, fine motor skills, self-help skills, communication, and cognition. Results indicated a general stagnation in all developmental areas beginning at approximately 15 months. No skills progressed beyond the 2-year level; this, despite several years of intensive, interdisciplinary intervention. Cognitive and communication skills regressed, then stabilized for several years, and subsequently began further regression. Gross motor and self-help skills appear to be areas of relative strength. PMID- 2329186 TI - Repetition deficits in three aphasic syndromes. AB - This study examined the repetition errors of three aphasic subgroups during a repetition task. A total of 95 subjects, including 32 conduction, 38 Broca's, and 25 Wernicke's aphasics, repeated phrases and sentences from the Repeating Phrases Subtest of the Boston Diagnostic Aphasia Examination. Conduction aphasics exhibited a greater number of phonemic attempts, word revisions, and word and phrase repetitions. Broca's aphasics demonstrated more phonemic errors and omissions. Finally, Wernicke's aphasics showed more unrelated words and jargon. PMID- 2329187 TI - Projections ascending from the spinal cord to the brain in petromyzontid and myxinoid agnathans. AB - The course of projections ascending through the rostral spinal cord to nuclei in the brains of petromyzontid and myxinoid agnathans was examined with silver staining of anterograde degeneration and horseradish peroxidase histochemistry. As in jawed vertebrates, the ascending spinal projections of lampreys and hagfishes appear to be organized into two major systems, the spinal lemniscal and dorsal column pathways. The spinal lemniscal pathway, extending rostrally along the ventrolateral margin of the spinal and medullary central gray, consists of a spinoreticular and possibly a spinovestibular projection in both aganthan groups. In Pacific hagfish, spinal lemniscal fibers reach the ipsilateral mesencephalic tectum, but no spinal projection to the thalamus was evident. The spinal lemniscus of lampreys ascends to the region of the isthmus and may extend into the mesencephalic tegmentum. Anterograde and retrograde tracing methods indicate that a very small population of cells in the far rostral cord of lampreys may project to the optic tectum and diencephalon; however, spinotectal and spinothalamic projections, if present, are limited in extent. The dorsal column pathway in agnathans, consisting in part of primary spinal afferents, ascends in the dorsal funiculus of the cord. The dorsal column fibers of agnathans, like those of some other anamniotes, continue beyond the spinomedullary junction through the length of the hindbrain, possibly conveying ascending somatosensory input to the sensory nuclei of the alar medulla. PMID- 2329188 TI - Disposition of the slab-like modules formed by axon branches originating from single CA1 pyramidal neurons in the rat hippocampus. AB - The hippocampus is thought to be an area where the neuronal circuits for short term memory or the cognitive map may reside. In order to advance theoretical studies and neuronal model simulations of such circuits, the projection of the CA1 pyramidal neurons in the rat dorsal hippocampus, especially in the subiculum, was studied by means of intracellular and extracellular HRP injection. The CA1 pyramidal neurons project principally to the subiculum where each forms a slab like axonal field 2 mm long along the septotemporal axis, which may be regarded as a module for columnar organization, at a specific rostrocaudal level of the subiculum. The modules of the CA1a pyramidal neurons are disposed in the rostral part of the subiculum, those of the CA1c pyramidal neurons in the caudal part, and those of the CA1b pyramidal neurons in the middle part of the subiculum. The CA1 pyramidal neurons also participate in the construction of the lamellar organization in the hippocampus in that their axon branches run rostrocaudally following the stream of the alvear fibers. The CA1 pyramidal neurons in the dorsal rat hippocampus transfer the topographic map from field CA1 to the subiculum with reversed order in the lamellar direction. The topographical relationship is composed of partially shifted, overlapping slab-like modules. As a result, information conveyed through a lamella will diverge into the subiculum approximately 2 mm wide, and information through a group of lamellae 2 mm wide will converge upon single subicular neurons. PMID- 2329189 TI - Cytological and quantitative characteristics of four cerebral commissures in the rhesus monkey. AB - The number, types, and distribution of distinct classes of axons and glia in four cerebral commissures of the adult rhesus monkey (Macaca mulatta) were determined using electron microscopic and immunocytochemical methods. The two neocortical commissures, the corpus callosum, and the anterior commissure contain small but cytologically distinct archicortical components: the hippocampal commissure, which lies ventral to the splenium of the corpus callosum, and the basal telencephalic commissure, which forms a small crescent at the anterior margin of the anterior commissure. Each archicortical pathway is delineated from the adjacent neocortical commissure by a glial capsule. The glia cells that form this border are immunoreactive with antisera directed against glial fibrillary acidic protein (GFAP) and issue long processes that form numerous desmosomal junctions with one another. Braids of these glial processes envelop axonal fascicles within the archicortical commissures. In contrast, the GFAP-positive cells of the corpus callosum and anterior commissure are randomly distributed cells with relatively short stellate processes that do not form boundaries around axon fascicles. Quantitative electron microscopic analysis reveals that approximately 60 million axons connect the two cerebral hemispheres: the corpus callosum contains 56.0 million +/- 3.8 million axons (n = 8), the anterior commissure contains 3.15 million +/- 0.24 million axons (n = 8), the hippocampal commissure has 237,000 axons +/- 31,000 (n = 6), and the basal telencephalic commissure has 193,000 axons +/- 28,000 (n = 5). The number of axons is not directly proportional to the cross-sectional area in any of the commissures because of variation in axonal composition. On the basis of an estimate of approximately 3 billion neurons in the monkey cortex (Shariff, '53), we estimate that between 2 and 3% of all cortical neurons project to the opposite cerebral hemisphere. Subregions of the corpus callosum as well as each of the other commissures consist of characteristic subsets of five classes of axons and contain different proportions of myelinated to unmyelinated fibers. The largest myelinated axons and the smallest proportion of unmyelinated axons (approximately 6%) are found in regions of the corpus callosum that carry projections from primary sensory cortices, whereas the smallest myelinated axons and largest proportion of unmyelinated axons (approximately 30%) are found in regions of the corpus callosum that carry projections from association cortices. Axon composition in the anterior commissure is uniform and resembles that of callosal sectors that contain association projections.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329190 TI - Zebrin II: a polypeptide antigen expressed selectively by Purkinje cells reveals compartments in rat and fish cerebellum. AB - Monoclonal antibody mab-zebrin II was generated against a crude homogenate of cerebellum and electrosensory lateral line lobe from the weakly electric fish Apteronotus leptorhynchus. On Western blots of fish cerebellar proteins, mab zebrin II recognizes a single polypeptide antigen of apparent molecular weight 36 kD. Immunocytochemistry of apteronotid brains reveals that zebrin II immunoreactivity is confined exclusively to Purkinje cells in the corpus cerebelli, lateral valvula cerebelli, and the eminentia granularis anterior. Other Purkinje cells, in the medial valvula cerebelli and eminentia granularis posterior, are not zebrin II immunoreactive. Immunoreactive Purkinje cells are stained completely, including dendrites, axons, and somata. The antigen seems to be absent only from the nucleus. A similar distribution is seen in catfish, goldfish, and a mormyrid fish. Zebrin II immunoreactivity is also found in the rat cerebellum. Western blotting of rat cerebellar proteins reveals a single immunoreactive polypeptide, with apparent molecular weight 36 kD, as in the fish. Also as in the fish, staining in the adult rat cerebellum is confined to a subset of Purkinje cells. Peroxidase reaction product is deposited throughout the immunoreactive Purkinje cells with the exception of the nucleus. No other cells in the cerebellum express zebrin II. At higher antibody concentrations, a weak glial cross reactivity is seen in most other brain regions: we believe that this is probably nonspecific. Zebrin II+ Purkinje cells are clustered together to form roughly parasagittal bands interposed by similar nonimmunoreactive clusters. In all there are 7 zebrin II+ and 7 zebrin II- compartments in each hemicerebellum. One immunoreactive band is adjacent to the midline; two others are disposed laterally to each side in the vermis; there is a paravermal band; and finally three more bands are identified in each hemisphere. Both in number and position, these compartments correspond precisely to the bands revealed by using another antibody, mabQ113 (anti-zebrin I). In both fish and rat the compartmentation revealed by zebrin II immunocytochemistry is related to the organization of cerebellar afferent and efferent projections and may provide clues as to the fundamental architecture of the vertebrate cerebellum. PMID- 2329191 TI - Demonstration of two separate descending noradrenergic pathways to the rat spinal cord: evidence for an intragriseal trajectory of locus coeruleus axons in the superficial layers of the dorsal horn. AB - The rat spinal cord receives noradrenergic (NA) projections from the locus coeruleus (LC) and the A5 and A7 groups. In contradiction to previous statements about the distribution of descending NA axons, we have recently proposed that in the rat LC neurons project primarily to the dorsal horn and intermediate zone, whereas A5 and A7 neurons project to somatic motoneurons and the intermediolateral cell column. The aim of the present study was to determine the funicular course and terminal distribution of descending NA axons from the LC and from the A5 and A7 groups. The organization of the coeruleospinal projection was analyzed by using the anterograde tracer Phaseolus vulgaris leucoagglutinin in combination with dopamine-beta-hydroxylase immunohistochemistry. The trajectory of A5 and A7 axons was studied in spinal cord sections of rats following ablation of the coeruleospinal projection with the neurotoxin DSP-4. To assess the relative contribution of the LC and the A5 and A7 groups to the NA innervation of the spinal cord, unilateral injections of the retrograde tracer True Blue were made at cervical, thoracic, and lumbar levels, and retrogradely labeled NA neurons were identified by dopamine-beta-hydroxylase immunofluorescence. The results of the anterograde tracing experiments confirm our previous findings that LC neurons project most heavily to the dorsal horn and intermediate zone. Analysis of horizontal sections revealed that LC axons descend the length of the spinal cord within layers I and II. In contrast to the intragriseal course of LC fibers, A5 and A7 axons travel in the ventral and dorsolateral funiculi and terminate in the ventral horn and the intermediolateral cell column. Retrograde transport studies indicate that the contribution of the A5 and A7 groups to the NA projection to the spinal cord is greater than that of the LC. We conclude that descending axons of the LC and A5 and A7 groups differ in their course and distribution within the spinal cord. The documentation of a definite topographic order in the bulbospinal NA projections suggests that the LC and the A5 and A7 groups have different functional capacities. The LC is in a position to influence the processing of sensory inputs, in particular nociceptive inputs, whereas A5 and A7 neurons are likely to influence motoneurons. PMID- 2329192 TI - Estradiol-concentrating forebrain and midbrain neurons project directly to the medulla. AB - The location and number of estradiol (E2)-concentrating neurons afferent to the dorsal medulla were determined by combining retrograde fluorescent tract tracing with steroid hormone autoradiography. Injections of Fluro-Gold were made into the medulla of 80 day old, ovariectomized, and adrenalectomized female rats. After 7 days survival to allow for retrograde transport, females were injected with [3H]estradiol; they were then perfused and their brains processed for steroid hormone autoradiography. Following a 4-12 month exposure period, autoradiograms were developed and microscopically analyzed for the presence of E2-concentrating neurons that project to the medulla. Numerous E2-concentrating neurons were identified that send axons directly to the medulla; the majority were found in the bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus, central nucleus of the amygdala, and the central gray. Of the E2 concentrating neurons in the bed nucleus of the stria terminalis, 12.7% also projected to the medulla. E2-concentrating neurons that sent axons to the medulla were also identified in and ventromedial to the lateral parvicellular subdivision in the caudal half of the paraventricular nucleus of the hypothalamus (69.4%). Over one-third of the E2-concentrating neurons found in the central nucleus of the amygdala coursed to the medulla. The central gray was the only mesencephalic brain region that contained E2-concentrating neurons that projected to the medulla (41.9%). The medulla-bound E2-concentrating forebrain and midbrain neurons identified in the present study may influence autonomic tone via direct projections. PMID- 2329193 TI - Musculotopic organization of the facial motor nucleus in Macaca fascicularis: a morphometric and retrograde tracing study with cholera toxin B-HRP. AB - Morphometric and retrograde tracing methods were used to determine the location and number of motoneurons innervating individual facial muscles in Macaca fascicularis. Intramuscular injections of the cholera toxin B subunit-horseradish peroxidase conjugate produced discrete labeling patterns in the ipsilateral facial motor nucleus with good definition of somata and their processes. The facial nucleus extended rostrocaudally in the pons for about 2 mm, varying in shape and cross-sectional area along this axis. Motoneurons were clustered in subnuclei, but their boundaries were not sharp and they were not segregated by fiber bundles. The length, number, and area of subnuclei varied with rostrocaudal location. Retrograde labeling patterns revealed that individual muscles were innervated by longitudinal columns of motoneurons with each muscle region represented at all rostrocaudal levels of its column. The columns began at different rostrocaudal levels and varied in length. Columns for closely related muscles, such as the orbicularis oris and mentalis of the lower lip, tended to overlap, whereas columns for disparate muscles, such as the perioral and orbital, did not overlap. The dendritic processes of most motoneurons branched extensively among several different columns or subnuclei. Some dendrites extended outside of the nucleus into the surrounding tegmentum. Mean soma diameter (10.4-42.2 microns) was distributed unimodally, reflecting the absence of gamma motoneurons and lack of muscle spindles in the facial muscles. Large and small motoneurons were found in all regions of the nucleus, but the largest ones were located caudally and innervated muscles of the upper and lower lip. The perioral muscles also had more neurons, longer columns, and a lower cell density than the other muscle groups examined. These features may reflect the functions of the perioral muscles in facial expression and vocalization. PMID- 2329194 TI - Neurogenesis of the magnocellular basal forebrain nuclei in the rhesus monkey. AB - The time of origin of the neurons that comprise the magnocellular basal forebrain nuclei in rhesus monkeys was determined by using [3H]thymidine autoradiography. Thirteen pregnant animals received an injection of [3H]thymidine between embryonic days 27 (E27) and E50 of their 165 day gestation, and their offspring were sacrificed during the early postnatal period. Neurons within this region were generated in a biphasic pattern. An initial burst of [3H]thymidine-labeled magnocellular neurons was first observed throughout short quiescent period, cells of the remaining anterior basal forebrain (inclusive of magnocellular neurons comprising the vertical limb of the diagonal band and the anteromedial and anterolateral regions of the nucleus basalis) were generated between E36 and E45 with a peak of neurogenesis seen on E40-E43. The intermediate division of the nucleus basalis was generated about the same time, but the peak period of neurogenesis in this region occurred slightly earlier (E36 and E40) and was completed by E43. During the second phase of neurogenesis, neurons within the posterior division of the basal forebrain were generated first, with their genesis virtually completed between E33 and E36. The genesis of all neurons comprising the magnocellular basal forebrain nuclei was completed by E48 of gestation. A general caudal to rostral gradient of neurogenesis was observed within this telencephalic region. In contrast, a neurogenic gradient was not discerned in the radial direction. The present data demonstrate that neurons comprising the basal forebrain magnocellular nuclei in monkeys are generated early in gestation with two peak times of neuronal genesis. These nuclei are among the earliest to be generated in the entire telencephalon, which, like neurons of the thalamus and cortical neurons giving rise to cortical-cortical connections, places them in a strategic position to potentially influence their target neurons within the cortical mantle that are generated later in gestation. PMID- 2329195 TI - Development of retinotopy in projections from the eye to the dorsal lateral geniculate nucleus and superior colliculus of the wallaby (Macropus eugenii). AB - The development of retinotopy in projections from the eye to the dorsal lateral geniculate (dLGN) and superior colliculus (SC) has been studied in the marsupial wallaby. Discrete retinal lesions were made and the remaining retinal projections were traced with horseradish peroxidase in animals at stages ranging from just after optic innervation of the dLGN and SC to the time when the projections are mature. Topographically organised projections could be recognized a few weeks after axons first reached the dLGN and SC with a topographically discrete projection from nasoventral retinal recognized later than from dorsal, dorso temporal, temporal, and temporoventral retina. Over time there was an increase in precision of the retinotopy as judged by an increase in sharpness of the borders of filling defects in the projection labelled with horseradish peroxidase. Refinement of the projection from temporal retina preceded that from nasal retina in both the dLGN and SC and in the former occurred concomitantly with the segregation of eye-specific terminal bands. Refinement was complete 16 weeks after birth, prior to eye opening at around 20 weeks after birth. Inequalities in retinal representations in both nuclei were present from the time retinotopy could first be detected. This was before the inequalities in retinal ganglion cell distribution, which underly these representations in the adult, were obvious. Retinotopy and inequalities in retinal representation characteristic of the adult are present from a very early stage in the protracted development of visual projections in the wallaby. Refinement may involve death of inappropriately projecting cells, pruning of inappropriately projecting axon arborizations or could be achieved by growth of the retinorecipient neuropil. Temporonasal differences in the time course of refinement may reflect gradients of maturation in the retina. PMID- 2329196 TI - Heterogeneity of chandelier neurons in monkey neocortex: corticotropin-releasing factor- and parvalbumin-immunoreactive populations. AB - Chandelier neurons are a unique subclass of cortical nonpyramidal neurons. The axons of these neurons terminate in distinctive vertically arrayed cartridges that synapse on the axon initial segment of pyramidal neurons. In this study, the rapid Golgi method and immunohistochemical techniques were used to characterize the morphology, regional distribution, laminar location, and biochemical content of chandelier neurons in the prefrontal and occipital cortices of three monkey species. As in our previous studies of visual areas V1 and V2 (Lund: Journal of Comparative Neurology 257:60-92, 1987; Lund et al.: Journal of Comparative Neurology 202:19-45, 1981, 276:1-29, 1988), Golgi impregnations of areas 46 and 9 of macaque prefrontal cortex show chandelier neurons to be present in layers 2 through superficial 5. The vertical arrays of terminal boutons (axon cartridges) typical of this neuron class are also present in layers 2-6 of the prefrontal cortex, but are not found in layer 1 or the subcortical white matter. In immunohistochemical studies, a calcium-binding protein, parvalbumin, and a neuropeptide, corticotropin-releasing factor (CRF), identify rod-like structures that are morphologically similar to the axon cartridges of chandelier neurons seen in the Golgi material. In addition, both parvalbumin- and CRF-immunoreactive cartridges are located below the somata of unlabeled pyramidal neurons and appear to outline the axon initial segment of these neurons. However, we find that parvalbumin and CRF are present in only subpopulations of chandelier axon cartridges. For example, in adult primary visual cortex, parvalbumin-labeled cartridges are present in very low numbers only in layers 2-3, whereas in prefrontal and occipital association cortices these cartridges are a very prominent component of layers 2-superficial 3 and are present in much lower density in the deeper cortical layers. In contrast to these findings in adult macaque monkeys, prefrontal and occipital association cortices of infant macaque monkeys contain a very high density of parvalbumin-labeled cartridges in layer 4 and relatively few in the superficial cortical layers. Furthermore, in adult squirrel monkey prefrontal cortex, CRF-labeled cartridges are predominately present in layer 4, but these CRF-immunoreactive structures have not been observed in the homologous regions of infant or adult macaque monkeys. These findings indicate that even for neurons of such distinctive morphology and presumably constant functional role as chandelier neurons, factors such as regional and laminar location, age, and primate species are associated with differences in the biochemical content of subpopulations of these neurons. PMID- 2329197 TI - Distribution of locus coeruleus axons within the rat brainstem demonstrated by Phaseolus vulgaris leucoagglutinin anterograde tracing in combination with dopamine-beta-hydroxylase immunofluorescence. AB - Projections of the locus coeruleus (LC) to the midbrain and hindbrain were analyzed by anterograde transport of the lectin Phaseolus vulgaris leucoagglutinin (PHA-L). Following iontophoretic application of PHA-L into the LC, the distribution of labeled axons was analyzed in sections processed for the immunoperoxidase method and in sections processed for double-immunofluorescence staining using antibodies to PHA-L and to dopamine-beta-hydroxylase. This combined staining approach proved to be necessary for the unequivocal identification of LC axons in the brainstem since all injections labeled many non noradrenergic axons whose distribution was different from that of LC fibers. The major new finding of the present study was the observation that large territories of the brainstem that receive a dense noradrenergic input are very sparsely innervated by the LC. Numerous labeled LC axons were observed in somatic afferent nuclei, tectum, pontine nuclei, interpenduncular nucleus, and inferior olivary complex. In contrast, very few labeled fibers were observed in autonomic and motor nuclei, and throughout the brainstem reticular formation, including raphe nuclei. Our data show that the distribution of LC axons in the brainstem is far less prominent than the projections of this nucleus to the forebrain and spinal cord. Our findings suggest that the dense NA projections to the core of the brainstem originate principally in non-LC NA neurons. On the basis of the present anatomical findings, a prominent role of the LC in motor and integrative functions of the brainstem appears unlikely. PMID- 2329198 TI - Postnatal development of palatal and laryngeal taste buds in the hamster. AB - Mammalian taste buds are distributed within several distinct subpopulations, innervated by branches of three cranial nerves. These taste bud populations originate and mature at different times in various mammalian species and are thought to play differential roles in the control of taste-mediated behaviors. The hamster is a common animal for the electrophysiological study of the gustatory system, and it has been shown that taste buds innervated by the IXth nerve develop postnatally in this species. To delineate further the development of the gustatory system of hamsters, we quantified the number of taste buds appearing on the palatal, nasopharyngeal, and laryngeal epithelium from birth through 120 days of age. Taste buds are present in almost adult numbers on the soft palate at birth, but only 39% of these are mature. Distinct taste pores, indicative of mature taste buds, increase in number until about 20-30 days of life, at which time all of the taste buds on the soft palate and on the nasoincisive papillae are fully developed. Taste buds are concentrated primarily on the posterior and medial portions of the soft palate. Taste buds located on the laryngeal surface of the epiglottis and the aryepiglottal folds are absent at birth and originate and mature over the following 120 days. Laryngeal taste buds are more concentrated on the aryepiglottal folds than on the epiglottis. On the soft palate and in the epiglottal region, the maturation of taste buds is well characterized by a logarithmic function (Y = a log X + B) relating the number of mature taste buds to postnatal age. On the soft palate, the length of the taste buds from base to apex correlates with the thickness of the epithelium, which increases with development. The diameter of mature taste buds on the soft palate does not change with age. In contrast to many mammalian species, in rodents taste bud development occurs mostly after birth. Rapid postnatal development progresses at a time when ingestive behavior is undergoing a number of significant changes. Taste buds in the larynx have been implicated in a number of laryngeal reflexes (i.e., apnea, swallowing) in several nonrodent species. The electrophysiological properties of superior laryngeal nerve fibers would suggest a similar function for epiglottal taste buds in the hamster. PMID- 2329199 TI - Electron microscopic study of immunocytochemically labeled centrifugal fibers in the goldfish retina. AB - The centrifugal fibers innervating the goldfish retina were studied quantitatively by light and electron microscopy. These fibers originating from cell bodies in the olfactory bulb were labeled by antiserum to the tetrapeptide Phe-Met-Arg-Phe-NH2 (FMRFamide). The number of FMRFamide-immunoreactive (ir) centrifugal fibers in each eye of the adult goldfish (body length: 12-15 cm) was 65 +/- 14 (mean +/- S.D., n = 7). All of these fibers in the optic nerve and the retina were unmyelinated. Each FMRFamide-ir centrifugal fiber runs along the optic fiber layer and gives several terminal arborizations in the outermost layer (layer 1) of the inner plexiform layer. Layer 1 is, therefore, densely covered by a plexus of terminal arborizations. Along these terminal arborizations, we found output synapses characterized by a cluster of small clear vesicles (40 nm in diameter) at the presynaptic site and a thickened membrane in the apposed retinal cell processes. In a sample area of 2,000 microns 2, such synapses occurred at a density of one per 105 microns 2, or about 13,000 per centrifugal fiber. Thus, the FMRFamide-ir centrifugal fibers are likely to modulate retinal cell activity through an estimated total of 840,000 output synapses per retina. PMID- 2329200 TI - Effects of feed intake and thermal stress on mammary blood flow and other physiological measurements in lactating dairy cows. AB - Six midlactation Holstein cows were exposed to treatments of thermal comfort environments with ad libitum or restricted (70% of ad libitum) DM intake and a thermal stress environment with ad libitum intake in two balanced 3 X 3 Latin squares to evaluate effects on mammary blood flow and other physiological measurements. Daily DM intake decreased from 17.8 kg in thermal comfort with ad libitum intake to 12.5 kg in thermal comfort with restricted intake and to 14.8 kg in thermal stress. Daily milk production decreased from 23.9 kg in thermal comfort ad libitum to 22.2 kg in thermal comfort restricted and 21.6 kg in thermal stress. Mammary blood flows (half udder) over the entire sampling interval (18 h) were 5.1, 4.3, and 4.5 L/min for treatments: thermal comfort, ad libitum intake; thermal comfort, restricted intake; and thermal stress, ad libitum intake. Mammary blood flows did not differ significantly among between treatments. Relationship of hald udder blood flow (L/min) to previous day's DM intake (kg/d) was described by the linear equation: L/min = .49 + (.27 kg/d); r2 = .46; and the quadratic equation: L/min = 6.04 - (.54 kg/d) + (.03 [kg/d]2); r2 = .55. Mammary blood flows 10 min before through 10 min after milking machine attachment were greater for cows at thermal comfort and ad libitum intake than for cows at thermal comfort and restricted intake or thermal stress and ad libitum intake (5.5, 4.8, and 4.8 L/min). PMID- 2329201 TI - Growth of Corynebacterium bovis in mammary secretions during physiological transitions of the bovine mammary gland. AB - An in vitro microassay was used to evaluate growth of five strains of Corynebacterium bovis in mammary secretions collected from quarters of five Holstein cows at 0, 14, and 28 d of involution, at parturition, and 14 d after parturition. Variation in growth among different strains of Corynebacterium bovis was observed. Corynebacterium bovis grew well in mammary secretions obtained at the last milking of lactation, at parturition, and 14 d after parturition. However, growth of four strains of Corynebacterium bovis in mammary secretions obtained at 14 and 28 d of involution was reduced significantly. In contrast, a streptomycin-resistant strain of Corynebacterium bovis grew well in mammary secretions obtained during involution. These data suggest that mammary secretions support growth of Corynebacterium bovis during lactation but inhibit growth during the nonlactating period. Inhibition of growth in secretions collected during the nonlactating period may be associated with the high rate of spontaneous elimination of Corynebacterium bovis intramammary infection from cessation of milking to parturition. Conversely, enhanced growth in milk may be related to persistent Corynebacterium bovis intramammary infections during lactation. PMID- 2329202 TI - Antimicrobial susceptibilities of staphylococcal species isolated from mammary glands of unbred and primigravid dairy heifers. AB - Staphylococcal isolates from teat canal keratin and mammary secretion samples of unbred and primigravid Jersey heifers were tested in vitro for susceptibility to 12 antimicrobial agents. More than 92% of the 311 isolates were susceptible to all antimicrobial agents tested. Staphylococci other than Staphylococcus aureus demonstrated an overall susceptibility of 98.3% to all antibiotics, and Staphylococcus aureus demonstrated a 97% susceptibility. Across all staphylococcal species, susceptibility of isolates from secretion samples was 98.1%, and susceptibility of isolates from teat canal keratin samples was 93.1%. Differences in susceptibilities were observed among herds. PMID- 2329203 TI - Relationships among selenium, vitamin E, and mammary gland health in commercial dairy herds. AB - Nine well-managed dairy herds were monitored for 1 yr to determine if bulk tank SCC and rate of clinical mastitis were associated with dietary and plasma Se and vitamin E status. Intakes of Se and vitamin E were 1 to 16 mg/d and 100 to 900 mg/d, respectively. Plasma Se concentrations were correlated positively with intakes of Se below 5 mg/d but were independent of Se intakes above 5 mg/d. Feeding vitamin E increased plasma concentrations of tocopherol, but the influence of dietary vitamin E on plasma concentrations was four times greater for dry cows than for lactating cows probably due to secretion of tocopherol into colostrum and milk. Bulk tank SCC averaged 5.4 log10/ml and decreased significantly as Se concentration in plasma increased. Plasma glutathione peroxidase was correlated positively to Se intake but negatively to SCC. Rate of clinical mastitis was negatively related to plasma Se concentration and concentration of vitamin E in the diet. An apparent interaction between dietary Se and vitamin E was evident since herds fed high amounts of Se tended to have high rates of clinical mastitis, but not if high amounts of vitamin E were fed. These data confirm earlier findings that Se and vitamin E status of dairy cows are related to mammary gland health. PMID- 2329204 TI - Iodine in milk and meat of dairy cows fed different amounts of potassium iodide or ethylenediamine dihydroiodide. AB - Relationships between I intake by lactating Holstein cows and iodine concentrations in milk and meat were investigated. Six treatment groups with seven cows assigned to each treatment were fed a basal diet containing .8 mg I/kg alone or supplemented with I at 1, 2, or 4 mg/kg in four 5-wk periods. Basal alone was fed in the first and third periods and the I supplement was potassium iodide in the second period and ethylenediamine dihydroiodide in the fourth period. Iodine concentrations in milk increased with each increase in dietary I from 205 ng/ml for basal periods to 404, 477, and 757 ng/ml when 1, 2, or 4 mg/kg I was fed as potassium iodide; and 467, 535, and 869 ng/ml when 1, 2, or 4 mg/kg I was fed as ethylenediamine dihydroiodide. Concentrations of I in skeletal muscle after the fourth period were not affected by 2 mg/kg I and only increased from 166 to 199 ng/g when supplemental I was 4 mg/kg. Moderate changes in dietary I are quickly reflected in milk I, but I in meat is relatively stable. PMID- 2329205 TI - Effect of subcutaneously released 24F-1,25-dihydroxyvitamin D3 on incidence of parturient paresis in dairy cows. AB - Twenty-one aged Jersey cows were fed a high calcium diet prior to parturition to predispose them to parturient paresis. Eleven cows were implanted subcutaneously with pellets containing 24F-1,25-dihydroxyvitamin D3 7 d before the expected date of parturition and thereafter at 7-d intervals until parturition. Ten cows were left untreated to serve as controls. Incidence of parturient paresis among control animals was 80% (8/10). Treatment reduced the incidence of parturient paresis to 9% (1/11). The mean observed plasma calcium concentration nadir of implanted cows was 6.61 +/- .40 mg/dl, which was significantly greater than the plasma calcium nadir of 4.45 +/- .39 mg/dl observed in the control cows. Two steers were implanted with and three nonpregnant, nonlactating cows received intramuscular injections of 24F-1,25 dihydroxyvitamin D3 to contrast circulating plasma concentrations achieved by the two routes. Intramuscular injection and implantation resulted in plasma 24F-1,25 dihydroxyvitamin D3 concentrations above 300 pg/ml for the first 48 h after administration. From d 4 until d 11 after administration, plasma concentration was maintained between 164 and 89 pg/ml in the implanted steers. Plasma concentration was undetectable 7 d after an intramuscular injection. These data indicate that, with refinement, sustained release of 24F-1,25 dihydroxyvitamin D3 can be successfully used to reduce the incidence of parturient paresis. PMID- 2329206 TI - Lactational responses to and in vitro ruminal solubility of magnesium oxide or magnesium chelate. AB - Thirty-six midlactation Holstein cows were used in a randomized incomplete block design to evaluate lactational responses to varying dietary concentrations of Mg supplemented by MgO or Mg chelate. Basal diet was 41:4:55 corn silage:cottonseed hulls:concentrate (.21% total Mg). Magnesium oxide was added to the basal diet to give .32, .37, and .43% total dietary Mg, and Mg chelate was added to provide .23, .25, and .27% Mg, DM basis. Dietary treatments were formulated to supply equal concentrations of bioavailable Mg from either Mg source. Dry matter intake and milk yield were greater by cows fed MgO-supplemented than Mg chelate supplemented treatments. Milk fat percentages were not affected. Milk protein percentages increased with Mg chelate compared with protein percentages with MgO. Treatments did not affect gross efficiency (4% FCM/DM intake) or body weight change. Lack of response to Mg chelate suggested that either the bioavailability was not as high as assumed or that sufficient total bioavailable Mg was not provided in those treatments. A companion in vitro experiment showed that MgO supplemented concentrates, with more total supplemental Mg, supplied two to three times more soluble Mg than Mg chelate-supplemented concentrates. PMID- 2329207 TI - Effect of magnesium administration route on plasma minerals in Holstein calves receiving either adequate or insufficient magnesium in their diets. AB - Rates of increase in plasma Mg following rectal or oral administration of solutions containing 30 g MgCl2.6H2O were compared in 10 Holstein bull calves receiving wheat straw (.07% Mg) and concentrates (.04 or .24% Mg) fed separately for ad libitum consumption. Treatments were administered in a sequence, which involved each calf with all combinations of MgCl2.6H2O dosing routes and dietary Mg within a 6-wk period. Plasma Mg concentration averaged 1.95 mg/dl initially but fell below 1 mg/dl within 2 wk after supplemental Mg was omitted. Maximum increases in plasma Mg concentration following oral or rectal dosing were 16 or 47% when dietary Mg was adequate and 48 or 124% when Mg was deficient. Calves fed either diet responded maximally to rectal infusion within 10 min, but plasma Mg of deficient calves increased throughout 160 min after oral dosing. Plasma Mg of deficient calves responded quicker and reached higher concentrations after rectal infusion, but the response was sustained longer after oral administration. PMID- 2329208 TI - Milk intake before first colostrum in newborn dairy calves. Effect on intestinal transmission of macromolecules. AB - The aim of this experiment was to investigate if ingestion of non-colostrum milk before first colostrum by calves impaired intestinal transmission of macromolecules from colostrum fed to calves 8, 16, and 24 h later. This design reflects the situation when calves are born in housing systems where the cow and her newborn calf are not separated from the herd, which gives the calf opportunity to suckle cows other than the mother. Two groups of eight calves each were fed pooled colostrum three times at 8, 16, and 24 h of age. One of the groups were fed non-colostrum milk 30 min after birth. Marker molecules were used to estimate absorption from each colostrum feeding. Blood samples were taken 8 h after each feeding and at 1 wk of age. At no time was there any significant difference between the plasma IgG means of the two groups. There was no difference in transmission of the marker molecules. It was concluded that early ingestion of non-colostrum milk before first colostrum does not change intestinal permeability to colostral macromolecules. PMID- 2329209 TI - Effect of variability in response to superovulation on donor cow selection differentials in nucleus breeding schemes. AB - The effectiveness of nucleus breeding schemes based on multiple ovulation and embryo transfer in practice is highly dependent upon the achieved reproductive rate. This study quantifies the effects of donor cow variability in response to superovulation (random and phenotypically correlated with milk yield) and failure rates (proportion of selected cows producing no transferable embryos) on the mean and variance of realized female selection differentials as affected by herd size, average embryo yield, and the coefficient of variation for embryo yield. Results show that differences in failure rates (0 to 40%) reduced realized female selection differentials up to 64%. The existence of a negative phenotypic correlation (-.3) between donor cow embryo yield and milk yield caused smaller reductions (up to 19%). Variability in realized female selection differentials is largest for small nucleus units and should not be neglected when planning the establishment of a nucleus breeding unit. The use of multiple flushes rather than a single flush per cow to produce the same average number of transferable embryos can reduce the variability in realized selection differentials but increases generation interval. Variability in response to superovulation will also affect inbreeding rates and the average accuracy of selection. Simulation studies are needed to quantify the total effect of variability in response to superovulation on the genetic responses possible in nucleus breeding schemes relying on multiple ovulation and embryo transfer. PMID- 2329210 TI - Divisional abstracts. PMID- 2329211 TI - A new method for culturing human hair follicle cells on floating mixed collagen membranes. AB - A new method for culturing human hair follicle cells without a biological feeder layer has been developed. Dispersed hair follicle cells obtained from plucked hairs have been successfully grown on floating mixed collagen membranes (collagen types I and IV) and have reached a confluent state. They could be subcultured up to twice. Differentiation of the cells was maintained throughout a month in culture. Stratification of the cells and continuous epithelial pavement formation were seen, as in cultured epidermal keratinocytes. PMID- 2329212 TI - Parallel arrangement, growth inhibition and cell cycle phase analysis of human dermal fibroblasts cultured in collagen lattice. AB - Human dermal fibroblasts were cultured in a hydrated type I collagen lattice. When collagen fibers were arranged in one direction, fibroblasts were arranged in the same direction. Cell proliferation was markedly suppressed in the collagen lattice as compared with that on plastic, with growth being arrested after day 5. No differences in proliferation were observed between aligned cells and randomly oriented cells. Flow cytometry with DNA staining was performed to analyze each phase of the cell cycle of fibroblasts. Among the 10,000 cell population, S phase cells on day 2 of culture accounted for 43% on plastic but were markedly inhibited to 25% in the lattice. On day 4, S phase cells accounted for 33% on plastic but only for 10% in the lattice. These findings suggest that cell advancement to the S phase is markedly inhibited in the collagen lattice, resulting in accumulation of most of cells in the G0G1 phase. The present study clearly showed that culture in the collagen lattice allowed alignment of fibroblasts with a definite orientation as observed in vivo and produced a status resembling that in vivo in terms of proliferation and cell cycle phase composition. PMID- 2329213 TI - Immunoblot demonstration of protein kinase C in pig epidermis. AB - Protein kinase C, which has an important role in cell surface signal transduction, has at least 7 subspecies. The role of each isozyme remains unknown; however, the distribution of the subspecies has been reported to differ from tissue to tissue. In order to investigate the subspecies of protein kinase C in epidermis, we used monoclonal anti-protein kinase C antibodies against the alpha and beta subspecies and against the gamma subspecies. Protein kinase C activity was detected in both cytosol and membrane bound fractions in the extract of pig epidermis, although with immunohistochemical analysis the enzyme was not detected in the epidermis. The protein kinase C in pig epidermis was extracted and partially purified with DE52 column chromatography and immunoblot analysis was performed. Western blot analysis with each anti-protein kinase C antibody showed protein kinase C of the alpha and/or beta subspecies in pig epidermis. The gamma subspecies of the enzyme was not demonstrated. Since this gamma subspecies has only been demonstrated in the brain, it is regarded not to be present in epidermis. The differing patterns of the expression of the multiple subspecies of protein kinase C may closely related to its specific function in each tissue. The subspecies of the enzyme expressed in the epidermis should be clarified further. PMID- 2329214 TI - A study of systemic and topical effects of topical steroid application through the comparison of two application schedules. AB - We compared two application schedules of a topical steroid, BV (Betamethasone valerate). The schedules were once daily and twice a week on juvenile Wistar rats treated for four weeks. Steroid actions were assessed topically (skin thickness and epidermal Langerhans cell density) and systemically (body weight and internal organ wet weights). The results revealed some rather severe systemic effects caused by frequent steroid application. And we also found a uniquely weak BV effect with Langerhans cells compared to obvious systemic effects on rats. We came to the conclusion that frequent steroid application to the young should be avoided. PMID- 2329215 TI - Psoriatic arthritis of the hands in seven adults. AB - Psoriatic arthritis is defined as an association of psoriasis with an arthropathy characterized mainly by osteolytic changes in the X-ray. To assess its frequency among Japanese psoriatic patients and to characterize their signs and symptoms, we examined 51 patients (37 males, 14 females) for arthropathy of the fingers. Seven patients (5 males, 2 females) had abnormal X-ray findings of the hands. They were compared with psoriatic patients without arthritis epidemiologically, clinically, and hematologically. Metacarpal indices were also measured and compared with the results from rheumatic arthritis patients and controls. PMID- 2329216 TI - Radio-active iodine uptake in vitiligo. AB - Vitiligo and thyroid disease are commonly associated disorders. Twenty-two clinically euthyroid vitiligo patients were studied for functional assessment of thyroid by radioactive iodine uptake assay. Half of them showed abnormal uptake values at 24 hours. Of these patients, 90% had lower values indicating a tendency towards developing hypothyroid state. Subclinical thyroid dysfunction in vitiligo appears to be an adaptive change. PMID- 2329217 TI - A human case of zoonotic onchocerciasis in Japan. AB - A 2-year-old girl living in southwestern Japan had a nodule of 2 months' duration on the left foot. A biopsy from the lesion showed transverse sections of a worm surrounded by granulomatous tissue. The worm was identified as an Onchocerca sp. from the morphological characteristics such as relatively thick cuticles, annular ridges on the cortical layer, and high somatic muscles. Positive serological tests using ELISA for Onchocerca gutturosa and Onchocerca volvulus supported the diagnosis. This was the first case of zoonotic Onchocerca infection detected in Japan. The clinicopathological aspects of zoonotic onchocerciasis of this case were discussed. PMID- 2329218 TI - A peculiar form of epidermotropism in cutaneous metastatic carcinoma. AB - A 71-year-old man developed metastatic cutaneous nodules of colon carcinoma on the scalp and chest wall. Histopathological findings revealed aggressive invasion of the tumor cells into the overlying epidermis (epidermotropic carcinoma); they occasionally adhered to the epidermal cells. These morphological features have not been described in cutaneous metastases from internal carcinomas. PMID- 2329219 TI - Amounts of fibrous proteins and matrix substances in hairs of different races. AB - Fibrous proteins (FPs) and matrix substances (MSs) were extracted as S carboxymethylated (SCM) derivatives from scalp hair of five individuals each of the Mongoloid, Negroid and Caucasoid races. The ratio of the extracted SCM FPs to SCM MSs in dry weight was calculated for each hair specimen. The ratios obtained from the Mongoloid hair were 0.45 +/- 0.03; those from the Negroid, 0.18 +/- 0.02; and those from the Caucasoid, 0.29 +/- 0.02. It has thus been suggested that the ratios of FP to MS contents in the hair may be involved in the determination of the macroscopic racial variations in the form of hair. PMID- 2329220 TI - Epidermal growth factor receptor mRNA is not increased in psoriatic skin. AB - Poly(A)+mRNAs were purified from the skin sheets of five psoriatic patients and three healthy individuals, and mRNA expression of epidermal growth factor (EGF) receptor gene was studied by Northern-blot technique using a cDNA probe of the whole EGF-receptor gene. Both psoriatic and normal skin had 5.3-kb and 11.0-kb mRNAs of the EGF-receptor gene. There existed no clear differences in the mRNA levels between psoriasis and normal controls. Since Nanney et al. has reported an increased number of EGF-receptors in active lesions of psoriasis, it has been speculated that the production of EGF-receptors is not increased, but rather that the down-regulation may be decreased, in psoriatic skin, resulting in the increased number of EGF-receptors. PMID- 2329221 TI - Cerebrotendinous xanthomatosis. AB - A case report on a 23-year-old female patient with cerebrotendinous xanthomatosis (CTX) is presented. From 8 years of age, the patient clinically showed multiple xanthoma masses on both knees, both heels, and the nasal bridge, juvenile cataracts, multiple abnormal neurologic dysfunctions, and dementia. The level of cholestanol in urine, serum, and xanthoma mass tissues was increased, as determined by capillary gas chromatography. PMID- 2329222 TI - Disseminated coccidioidomycosis. AB - We report a case of disseminated coccidioidomycosis in a 39-year-old Japanese male whose illness developed after returning from a trip to an endemic area. He showed positive coccidioidin skin reaction throughout the entire course of his illness. The primary lesion in the lung subsequently spread to the bone. While the patient was on treatment with 5-FC, he made another trip to the same endemic area. After this episode, he developed pulmonary symptoms and cutaneous nodules on his wrist. The possibility of reinfection with Coccidioides immitis is discussed. Electron microscopy of the cutaneous nodules revealed that the spherules examined maintained their structural integrity in the granulomatous lesion, suggesting the high viability of the organism. Host-parasitic interaction in coccidioidomycosis is discussed. PMID- 2329223 TI - A case of sclerosing lymphangitis of the lip. AB - A 62-year-old woman noted a cord-like swelling on the inner surface of her upper lip. A cross-section of the lesion showed a radial-shaped lumen surrounded by a thickened fibrous wall. Immunohistochemical staining with the anti-factor VIII related antigen (FVIII-RAg) antibody was negative on the luminal surface and swollen wall, although the vasa vasorum in the swollen wall were positive. The lesion was thus considered to be of lymphatic origin; that is, it derived from a lymphatic collecting vessel. For the present case, the term 'lymphangiopathia obliterans' is considered appropriate. This is the second report of such a lesion appearing on the lip in the literature. PMID- 2329224 TI - Pseudoelephantiasis of the penis following donovanosis. AB - Pseudoelephantiasis of the penis, an unusual sequel of longstanding donovanosis with otherwise characteristics clinical expression, is reported in a young man. The diagnosis was confirmed by the demonstration of Donovan bodies in Giemsa stained tissue smears and tissue sections. PMID- 2329225 TI - Poikiloderma-like lesions on the neck in atopic dermatitis: a histopathological study. AB - Reticulate pigmentation with or without skin atrophy, depigmentation and telangiectasia is frequently encountered on the neck of severe cases of adult type atopic dermatitis. These skin changes were graded clinically into 3 stages. Based on histological features, hyperplasia of the sebaceous gland, dilated tortuous capillaries, and mild degeneration of elastic fibers were noted in stage I lesions. Lesions of both stages II and III contained increased melanin in the basal cell layer with incontinence of pigment, remarkable destruction and degeneration of elastic fibers, proliferated and dilated capillaries, and deposition of mucinous substances. The numbers of mast cells in papillary dermis were significantly increased in late stage I and stage II lesions. Poikiloderma like lesions on the neck could be attributable to chronic inflammation and delay of wound healing process, possibly caused by long-standing topical corticosteroid therapy. PMID- 2329226 TI - The diagnostic and prognostic role of cardiovascular ultrasound in endocarditis: bigger is not better. PMID- 2329227 TI - Acute myocardial uptake of digoxin in humans: correlation with hemodynamic and electrocardiographic effects. AB - Acute myocardial uptake of digoxin was measured at a constant paced heart rate (75 beats/min) for 30 min after an intravenous bolus injection of 500 micrograms of digoxin in 14 patients with ischemic heart disease. Myocardial digoxin content, determined by serial measurement of aortocoronary sinus digoxin concentration gradients and coronary sinus blood flow, was expressed relative to coronary sinus blood flow at rest and correlated with simultaneous hemodynamic and electrocardiographic changes. Myocardial digoxin uptake was extensive (4.1 +/ 0.7% of total injected dose at 30 min) and prolonged, with rapid initial uptake (75.3 +/- 6.6% of maximum at 3 min), followed by a variable phase of slower accumulation. Peak left ventricular positive first derivative of left ventricular pressure (dP/dt) increased progressively (p less than 0.01), with a similar time course to that of myocardial digoxin accumulation; maximal change was 18.5 +/- 4.7% at 27 min. The ratio of inotropic effect to myocardial digoxin content did not vary significantly over the period of the experiment. However, peak inotropic effects in individual patients were not significantly related to peak myocardial digoxin content. The spontaneous PR interval increased transiently, with a peak increase of 5.9 +/- 1.8% (p less than 0.05) 12 min after digoxin administration. It is concluded that after intravenous bolus administration, 1) peak effects of digoxin on atrioventricular (AV) conduction occur early, whereas positive inotropic effects increase progressively for greater than or equal to 27 min; and 2) digoxin accumulation in the human myocardium is prolonged and is a determinant of inotropic effects, but not of prolongation of AV node conduction. PMID- 2329228 TI - Urgent parenteral digoxin therapy: a requiem. PMID- 2329229 TI - Occlusion after coronary revascularization. PMID- 2329230 TI - The signal-averaged electrocardiogram and ventricular arrhythmias after thrombolysis for acute myocardial infarction. AB - The prevalence of an abnormal signal-averaged electrocardiogram (ECG) and ventricular arrhythmias on 24 h ambulatory electrocardiography was evaluated in 118 patients 13 +/- 2 days after acute myocardial infarction. Group 1 (46 patients) underwent intravenous thrombolysis within 6 h of the onset of symptoms, whereas Group 2 (72 patients) did not. An abnormal signal-averaged ECG was seen in 15% of patients in Group 1 and 21% of those in Group 2 (difference not significant). The number of ventricular premature complexes/h was lower in Group 1 than in Group 2: 2.58 +/- 1.63 versus 7.91 +/- 10.75 (p less than 0.01). However, complex arrhythmias (greater than or equal to 10 ventricular premature complexes/h or ventricular tachycardia) were equally common in Groups 1 and 2 (20% versus 22%, respectively). Their prevalence was similar in patients with or without an abnormal signal-averaged ECG (29% versus 18%, respectively, in Group 1 and 27% versus 21%, respectively, in Group 2). Comparison between patients with (n = 26) or without (n = 20) angiographic patency of the infarct-related coronary artery after thrombolysis showed no significant difference in the prevalence of an abnormal signal-averaged ECG (8% versus 25%, respectively) and complex ventricular arrhythmias (19% versus 20%, respectively). These data suggest that thrombolysis does not affect the prevalence of complex ventricular arrhythmias and an abnormal signal-averaged ECG or their relation after acute myocardial infarction. PMID- 2329231 TI - Thrombolytic therapy, infarct vessel patency and late potentials: can the arrhythmic substrate be altered? PMID- 2329232 TI - Atrial fibrillation in hypertrophic cardiomyopathy: a longitudinal study. AB - The clinical outcome of 52 consecutive patients with hypertrophic cardiomyopathy who developed paroxysmal (less than 1 week) or established (greater than or equal to 1 week) atrial fibrillation between 1960 and 1985 was examined retrospectively and compared with that of a matched group of patients with hypertrophic cardiomyopathy and sinus rhythm. Follow-up study until death or the present ranged from 6 months to 24 years (median 11 years) from diagnosis and from 6 months to 22 years (median 7 years) from the onset of atrial fibrillation. Atrial fibrillation was present in 6 patients at the time of diagnosis, whereas it developed subsequently in 46. The acute onset of arrhythmia was associated with a change in symptoms in 41 (89%) of the 46. After initial treatment of acute atrial fibrillation, sinus rhythm was restored in 29 (63%) of the 46 patients; 43 (93%) of the 46 returned to their original symptom class. Stepwise logistic regression revealed that shorter duration of arrhythmia and amiodarone therapy were the most powerful predictors of return to sinus rhythm. Sinus rhythm was maintained during a median follow-up period of 5.5 years in 22 of the 29 patients in whom it was restored after initial therapy. During follow-up study, 25 of the 52 patients were treated with conventional therapy alone and 7 with amiodarone alone. Amiodarone therapy was associated with maintenance of sinus rhythm, fewer alterations in drug therapy, fewer embolic episodes and fewer attempted direct current cardioversions (during a shorter follow-up period).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329233 TI - Hypertrophic cardiomyopathy and atrial fibrillation: a change of perspective. PMID- 2329234 TI - Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics. AB - Left ventricular systolic function does not correlate well with functional class in patients with dilated cardiomyopathy. To determine whether the correlation is better with Doppler indexes of left ventricular diastolic function, 34 patients with dilated cardiomyopathy (M-mode echocardiographic end-diastolic dimension greater than 60 mm, fractional shortening less than 25%, increased E point-septal separation) were studied. Patients were classified into two groups according to functional class. Group 1 consisted of 16 patients in New York Heart Association functional class I or II; group 2 included 18 patients in functional class III or IV. Left ventricular dimensions, fractional shortening, left ventricular mass, meridional end-systolic wall stress, peak early and late transmitral filling velocities and their ratio, isovolumetric relaxation period and time to peak filling rate were computed from pulsed wave Doppler and M-mode echocardiograms and calibrated carotid pulse tracings. Right heart catheterization was performed in 20 of 34 patients. No differences were observed between groups with regard to age, gender distribution, heart rate, blood pressure and M-mode echocardiographic derived indexes of systolic function. Peak early filling velocity (72 +/- 13 versus 40 +/- 10 cm/s, p less than 0.001) was higher and atrial filling fraction (27 +/- 4% versus 46 +/- 8%, p less than 0.001) was lower in group 2 than in group 1. The ratio of early to late transmitral filling velocities was higher in group 2 patients (2.3 +/- 0.5 versus 0.7 +/- 0.2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329235 TI - Cholesterol embolization: clinical findings and implications. AB - The clinical characteristics of 13 patients with cholesterol embolization are described. Embolization occurred spontaneously in 2 patients and after a vascular procedure in 11. Acute but vague symptoms were reported by 11 of the 13 patients; skin findings of purple toes or livedo reticularis and renal dysfunction were present in 12 patients, 5 of whom required dialysis. Blood pressure elevation occurred in all 13 patients, eosinophilia in 9 of 10 and elevated sediment rate in 5 of 6. Death occurred within 6 months in three patients. Two distinct patterns were observed: mild (five patients) and severe (eight patients). Compared with the severe pattern, patients with mild cholesterol embolization had early symptoms less frequently (two of five versus eight of eight), less severe renal insufficiency (serum creatinine 1.7 versus 7.4 mg/100 ml), less of an increase in blood pressure (22 versus 34 mm Hg) and later development of skin lesions (14 versus 6 weeks). Baseline blood pressure and development of eosinophilia were comparable in both groups. The presentation of cholesterol embolization is often subtle and may go unrecognized, particularly in its mild form. As vascular interventions increase in elderly atherosclerotic and hypertensive patients, so too will the incidence of this disorder. PMID- 2329236 TI - Atrial septal defect after percutaneous mitral balloon valvuloplasty: immediate results and follow-up. AB - Percutaneous mitral balloon valvuloplasty was performed in 150 patients. There were 124 women and 26 men (mean age 53 +/- 1 years). A left to right shunt through the created atrial communication was present in 28 patients (19%) after valvuloplasty. The pulmonary to systemic flow ratio was greater than or equal to 2:1 in 4 patients and less than 2:1 in 24. Univariate predictors of left to right shunting after valvuloplasty included older age (p less than 0.01), lower cardiac output before mitral valvuloplasty (p less than 0.01), higher New York Heart Association functional class before valvuloplasty (p less than 0.05), presence of mitral valve calcification under fluoroscopy (p less than 0.01) and higher echocardiographic score (p less than 0.05). Multiple stepwise logistic regression analysis identified the presence of mitral valve calcification (p less than 0.02) and lower cardiac output (p less than 0.02) as the independent predictors of a left to right shunt through the atrial communication after balloon valvuloplasty. Follow-up (10 +/- 1 months) of patients with an atrial septal defect after valvuloplasty showed that 1) 6 patients died (3 in the hospital and 3 at 2, 16 and 18 months, respectively, after valvuloplasty); 2) an atrial septal defect was demonstrated in 3 of 6 patients who underwent mitral valve replacement (6 +/- 0.8 months after valvuloplasty); and 3) 13 patients were in functional class I, 2 patients were in class II and 1 patient was in class III at 13 +/- 1 months after valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329237 TI - The heart in orthostatic hypotension. PMID- 2329238 TI - Sustained intraatrial reentrant tachycardia: clinical, electrocardiographic and electrophysiologic characteristics and long-term follow-up. AB - Although intraatrial reentry has been traditionally listed as a mechanism for supraventricular tachycardia, few reports describing the clinical features of this arrhythmia exist. Nineteen patients with a clinical history of sustained supraventricular tachycardia were diagnosed as having intraatrial reentrant tachycardia. Seventeen (89%) patients of the 19 had underlying structural heart disease and 17 had echocardiographic evidence of atrial enlargement; the mean left ventricular ejection fraction was 51 +/- 16%. A history of concomitant atrial fibrillation or flutter was present in 13 patients (68%). The mean atrial cycle length during tachycardia was 326 +/- 57 ms (range 260 to 460). Fourteen patients had 1:1 atrioventricular (AV) conduction during tachycardia, of whom 50% had an RP'/RR' ratio greater than 0.5. Intravenous adenosine (dose range 37.5 to 150 micrograms/kg) and verapamil (dose range 5 to 10 mg) had no effect on atrial tachycardia cycle length in 13 of 14 and 9 of 9 patients, respectively, despite induction of second degree AV block. Type 1a antiarrhythmic drugs achieved long term suppression of intraatrial reentrant tachycardia in only 6 patients, whereas amiodarone (326 +/- 145 mg/day) was successful in 11 patients during a 32 +/- 20 month follow-up period. The remaining two patients and one patient who later developed amiodarone toxicity either progressed to (n = 1) or had (n = 2) catheter-induced high grade AV block and were treated with long-term ventricular pacing. It is concluded that intraatrial reentrant tachycardia is often associated with structural heart disease, particularly of types that cause atrial abnormalities, but left ventricular dysfunction is not a requisite finding. Other arrhythmias are frequently observed in these patients. This arrhythmia responds poorly to type 1a antiarrhythmic drugs, but is effectively treated with amiodarone. Catheter ablation of the AV junction offers a therapeutic option for patients who are refractory to medical therapy. PMID- 2329239 TI - Distinguishing viable from infarcted myocardium after experimental ischemia and reperfusion by using nuclear magnetic resonance imaging. AB - Early reperfusion has the potential for salvaging ischemic myocardium at risk for infarction. To test the ability of nuclear magnetic resonance (NMR) imaging to differentiate between stunned and infarcted myocardium early after reperfusion, 16 mongrel dogs underwent transient occlusion of the left anterior descending artery or a diagonal branch for 30, 60 or 180 min followed by reperfusion. To identify the area at risk for infarction and to assess the extent of hypoperfusion and reperfusion, two-dimensional and contrast echocardiography were performed at baseline study, during coronary occlusion and at three separate times during reperfusion (before NMR imaging, immediately after NMR imaging and 12 to 14 h later). Wall thickening in the control and ischemic zones and the circumferential extent of abnormal wall motion were analyzed at each time point using short-axis echocardiograms. Nuclear magnetic resonance imaging at 1.5 tesla was performed 2 to 3.5 h (mean 2.7 +/- 0.5) after reperfusion. Short-axis, multislice spin-echo images (TE 26 and TE 60) were obtained. Signal intensity was measured in the control and ischemic areas and expressed as a percent difference compared with normal myocardium. All dogs demonstrated a significant decrease in wall thickening and abnormal wall motion before and after NMR imaging. Seven of the eight dogs with infarction had an area of increased signal intensity on TE 60 images. The mean percent difference in signal intensity compared with adjacent normal myocardium was 127 +/- 68% (p = 0.002). None of the eight dogs without infarction had a visually apparent change in signal intensity on TE 60 images (mean percent difference versus control area 13 +/- 11%), despite regional systolic dysfunction documented by echocardiography at the time of imaging. The area of increased signal intensity correlated with infarct size (r = 0.69), although overestimation by NMR imaging occurred. The area of increased signal intensity did not correlate with the extent of echocardiographic contrast defect during coronary occlusion (risk area). This study demonstrates that NMR imaging can be applied early after coronary reperfusion to assess the potential for recovery of dysfunctional myocardium. In addition, by using a TE 60 multislice spin-echo imaging sequence at 1.5 tesla, quantification of the extent of infarction also may be possible. PMID- 2329240 TI - Late potentials on the signal-averaged electrocardiogram after canine myocardial infarction: correlation with induced ventricular arrhythmias during the healing phase. AB - Signal-averaged electrocardiograms (ECGs) and programmed ventricular stimulation were serially performed in 12 dogs (3 weeks of age) after experimental anteroapical myocardial infarction. At electrophysiologic study, sustained ventricular tachyarrhythmia was induced in seven dogs on at least one occasion. Of a total of 39 electrophysiologic studies, sustained monomorphic ventricular tachycardia was induced in seven studies and ventricular fibrillation in eight studies. In the remaining studies, no ventricular arrhythmia could be induced with triple ventricular extrastimuli. There was considerable day to day variability in the response to programmed stimulation and the results of the signal-averaged ECG. The signal-averaged QRS complex was significantly longer in dogs with inducible ventricular tachycardia or fibrillation (61 +/- 5 versus 57 +/- 3 ms, p = 0.02), had a lower terminal QRS amplitude (24 +/- 20 versus 46 +/- 33 microV, p = 0.04) and a longer late potential duration (19 +/- 4 versus 15 +/- 3 ms, p = 0.003) compared with that in animals with no inducible ventricular arrhythmia. Late potentials were defined as a total QRS duration greater than 58 ms, a terminal QRS amplitude less than 20 microV and a late potential duration greater than 18 ms. Using this definition, late potentials were seen in two distinct phases--immediately after coronary ligation and then beyond the first 72 h after infarction. The appearance of late potentials coincided with a change in arrhythmia inducibility from no ventricular arrhythmia to initiation of sustained monomorphic ventricular tachycardia. There is a close relation between inducibility of ventricular tachycardia in experimental canine myocardial infarction and the appearance of late potentials on the surface ECG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329241 TI - Reduction in reperfusion injury by blood-free reperfusion after experimental myocardial infarction. AB - Because myocardial reperfusion injury may be caused by various blood constituents, a transient period of blood-free reperfusion was evaluated in closed chest dogs subjected to a 90 min angioplasty balloon occlusion of the left anterior descending coronary artery. In the treated group (n = 13), the balloon remained inflated for an additional 15 min while the infarct vessel was perfused with an acellular oxygenated perfluorochemical emulsion (Fluosol). The balloon was then deflated, permitting blood reperfusion. In the control group (n = 13), the balloon was deflated after 90 min of coronary occlusion. One week after infarction, the area at risk was defined in vivo by monastral blue dye staining, and the area of myocardial necrosis was assessed using triphenyltetrazolium chloride staining with histologic confirmation. Major determinants of infarct size, including rate-pressure product, area at risk and severity of myocardial ischemia (assessed by the extent of ST segment elevation during coronary occlusion), were not significantly different in the two groups. Treated dogs demonstrated a 47% reduction in infarct size expressed as a percent of the area at risk compared with control dogs (27.0 +/- 4.4% versus 50.8 +/- 4.4%, p less than 0.01). Treated dogs also demonstrated a superior global left ventricular ejection fraction (57.5 +/- 2.5% versus 51.0 +/- 2.2%, p less than 0.05) and anterolateral (regional) ejection fraction (32.6 +/- 3.6% versus 19.8 +/- 3.9%, p less than 0.05) compared with values in control dogs assessed by contrast ventriculography after 1 week of reperfusion. It is concluded that a transient period of blood-free reperfusion with an oxygenated perfluorochemical reduces reperfusion injury in a canine model of myocardial infarction. PMID- 2329242 TI - Echocardiographic spectrum of double inlet ventricle: evaluation of the interventricular communication. AB - To determine the spectrum and associated anomalies of double inlet ventricle (single ventricle), echocardiographic data of 50 patients with double inlet ventricle were reviewed and compared with the data obtained by cardiac catheterization, cardiac surgery and autopsy. Standard echocardiographic planes were used to determine the cardiac anatomy and the size of the interventricular communication. Double inlet by way of two perforate valves was found in 44 patients. In 42 of the 44 patients the dominant ventricular morphology was of the left ventricular type (double inlet left ventricle); in 13 of these 42 patients stenosis of one atrioventricular (AV) valve was found. Double inlet right ventricle and double inlet indeterminate ventricle were each found in one patient. Double inlet by way of a common AV valve was found in six patients, all of whom had atrial isomerism. The diagnosis of double inlet ventricle was accurate by two-dimensional echocardiography in all 44 patients. A restrictive interventricular communication was shown in 13 patients and a nonrestrictive communication in 17 patients by cardiac catheterization. Patients with a restrictive interventricular communication had a significantly smaller interventricular communication area normalized by the body surface area (mean +/- SD 1.21 +/- 0.53 cm2/m2) than did those with a nonrestrictive interventricular communication (2.33 +/- 0.71 cm2/m2) (p less than 0.01). Infants with an aortic anomaly had a significantly smaller interventricular communication area (1.35 +/- 0.65 cm2/m2) than did those without an aortic anomaly (2.57 +/- 0.76 cm2/m2) (p less than 0.05). Echocardiography provides an accurate noninvasive diagnosis in patients with double inlet ventricle, offering reliable information about the restrictive interventricular communication. PMID- 2329243 TI - Echocardiographic analysis of regional left ventricular wall motion in normal children and neonates. AB - Because comprehensive normal data and the effect of observer variability for echocardiographic evaluation of regional left ventricular wall motion are not available in children or newborns, left ventricular wall motion was assessed by measuring regional area change. The study group comprised 55 infants and children with a normal heart: 15 neonates (greater than 1 week to less than 1 month old), 10 infants (greater than 1 month to less than 1 year old) and 30 children, 10 each in the age group greater than 1 year to less than 5 years, greater than 5 to less than or equal to 10 years and greater than 10 years. A combination of parasternal, apical and subcostal two-dimensional echocardiographic views was applied. After planimetry of an end-systolic and end-diastolic frame, the left ventricle was divided into eight equal segments and the percent area change calculated. Both a fixed reference and a floating system correcting for translation and rotation were applied. Intraobserver variability for percent area change measurements was 2.8 +/- 0.9% and 3.8 +/- 1% for observers 1 and 2, respectively. The mean interobserver difference of regional percent area change was 4.7 +/- 1.8%. Normal values for the eight anatomic segments were established in each echocardiographic imaging plane. The overall results were independent of the type of reference system utilized. The subcostal views yielded different results from their parasternal counterparts, probably because of differing imaging planes. These normal values establish a data base in the pediatric age range that can be used to detect abnormal segments in children at risk for developing regional left ventricular wall motion abnormalities. PMID- 2329244 TI - Echocardiographic analysis of regional left ventricular wall motion in children after the arterial switch operation for complete transposition of the great arteries. AB - Regional left ventricular wall motion was assessed by two-dimensional echocardiography in 21 patients with complete transposition of the great arteries at a mean of 2.2 years (range 0.3 to 7) after an arterial switch operation. Fourteen patients had undergone a two-stage and seven patients a primary repair. Twenty patients were found to have echocardiographic images adequate for wall motion analysis. The results of these studies were correlated with thallium-201 myocardial perfusion scans. Left ventricular wall motion was assessed by measuring regional area change in parasternal and apical views. After planimetry of an end-systolic and an end-diastolic frame, the ventricle was divided into eight equal segments and the percent area change was calculated. Both a fixed reference and a floating system correcting for translation and rotation were applied. The measurements in the patient group were compared with normal age matched values previously obtained in 55 normal infants and children. Wall motion abnormalities, found in seven patients, were located at the apex in three, at the inferior septum and anterolateral wall in one and the inferior, anterolateral and lateral walls in one patient each. All had a myocardial perfusion defect in a corresponding anatomic location. One patient with a small reversible perfusion defect at the basilar septum had normal regional wall motion. The sensitivity of detecting impairment of myocardial perfusion was 0.95. Wall motion abnormalities were found only in patients who had undergone a two-stage repair. Echocardiographic wall motion analysis can be used as a screening method to identify patients with suspected myocardial ischemia after the arterial switch operation. PMID- 2329245 TI - Exercise responses in patients with congenital heart disease after Fontan repair: patterns and determinants of performance. AB - After a Fontan repair for congenital heart disease, 42 patients underwent graded supine bicycle exercise tests at levels relevant to normal daily activities. Results were compared with those of 28 age-matched normal control subjects. At rest, the cardiac index, stroke index and systolic blood pressure were comparable in both groups, but increases with exercise were smaller in the patients with a Fontan circulation. The heart rate at rest was higher in the Fontan group, but this difference disappeared as soon as exercise started. To determine whether there are limitations intrinsic to the Fontan circulation at these levels of exercise, the 10 best performers were compared with 10 age-matched control subjects; no differences were found in cardiac index, stroke index, heart rate or blood pressure at any exercise level. Analysis of the determinants of cardiac output showed that at the other end of the spectrum poor performance after a Fontan operation did not result from inadequate levels of heart rate, but from an inability to increase or maintain stroke volume. Multivariate analysis demonstrated that impairment of ventricular contractility, only when severe, predicted limited performance. There was no evidence of increased afterload, particularly in the poor performers. Therefore, ventricular filling, which is determined primarily by the pulmonary vascular bed, appears to be a major determinant of functional result after a Fontan repair. PMID- 2329246 TI - Coronary artery diameters in the heart with complete transposition of the great vessels. AB - The use of echocardiography established values for dimensions of normal coronary arteries in the setting of the heart with complete transposition (concordant atrioventricular and discordant ventriculoarterial connections) was evaluated. The diameters of the proximal coronary arteries measured at autopsy in 20 patients with complete transposition who had or had not undergone surgery were directly comparable with values determined in normal hearts by two-dimensional echocardiography. The values showed a linear increase with age, weight and length of the patients despite different branching patterns of the coronary arteries. Although there was right ventricular hypertrophy in all cases, the orifices of the right and left coronary arteries did not show any significant difference in diameter. Histologic examination and measurement of the arteries also revealed findings comparable with those in normal hearts. These findings suggest a relatively constant developmental pattern of the proximal coronary arteries despite different hemodynamics between the concordantly connected heart and the heart with complete transposition. In contrast, the functional significance of the stiff and slitlike orifices of the coronary arteries and their comparatively small diameters in relation to the ventricular wall thickness in four hearts studied after the arterial switch procedure for transposition merit further investigation. PMID- 2329247 TI - Doppler color flow mapping in the diagnosis of ventricular septal rupture and acute mitral regurgitation after myocardial infarction. AB - Fifty consecutive patients with a newly acquired systolic murmur and severe cardiac decompensation following a recent myocardial infarction (27 with an anterior and 23 with an inferior infarct) were studied by a combination of two dimensional echocardiography, spectral Doppler and Doppler color flow mapping. The initial ultrasound study defined a ventricular septal rupture in 43 patients and severe isolated mitral regurgitation in 7 patients (5 with papillary muscle rupture and 2 with severe papillary muscle dysfunction). All 50 patients had subsequent confirmation of the diagnosis by either cardiac catheterization or surgical inspection, or both. Two-dimensional echocardiography alone directly visualized a septal defect in only 17 (40%) of the 43 patients with ventricular septal rupture. In all 43 patients the mitral valve appeared normal on imaging. In six of the seven patients with isolated mitral regurgitation, two-dimensional echocardiography correctly demonstrated the structural abnormality of the mitral valve (five with flail anterior leaflet and one with posterior leaflet prolapse). The addition of Doppler color flow mapping greatly improved the diagnostic information in both patient groups. In all 43 patients with ventricular septal rupture, Doppler color flow mapping demonstrated both an area of turbulent transseptal flow and a diagnostic systolic flow disturbance within the right ventricle. In the seven patients with isolated papillary muscle rupture or dysfunction, Doppler color flow mapping not only demonstrated the presence of mitral regurgitation in all cases, but also identified the specific mitral leaflet abnormality by defining the direction of the regurgitant jet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329248 TI - Lack of an association between the presence of tumor necrosis factor or interleukin-1 alpha in the blood and weight loss among elderly patients. AB - To determine the association between blood cytokine levels and body weight loss in elderly patients, serum levels of cachectin/tumor necrosis factor alpha (TNF) and interleukin-1 alpha (IL-1) were measured with specific and sensitive ELISA systems. Of the 19 healthy young subjects, two (10.5%) had detectable levels of serum TNF and one (5.3%) was positive for IL-1. In the healthy elderly group, two of the 12 subjects (16.7%) had measurable TNF levels and four (33.3%) had elevated IL-1 levels. Of the 61 ambulatory elderly patients, 31.1% had serum that contained TNF and 22.9% had IL-1. Similar proportions were found in 127 nursing home patients. None of the common diseases examined in this study nor any commonly used medications were associated with increased serum cytokine levels. Patients with weight loss of more than 5 lbs were less likely to have elevated serum TNF and IL-1 levels compared to the rest of the group. It is concluded that although elevated levels of TNF or IL-1 may occur more frequently in older groups, there is no evidence for a causal relationship between these circulating cytokines and clinically significant weight loss in the elderly. PMID- 2329249 TI - Early natural menopause and the duration of postmenopausal life. Findings from a mathematical model of life expectancy. AB - Menopause marks the beginning of a stage of life characterized by an increased susceptibility to diseases such as coronary heart disease and osteoporosis. It was therefore hypothesized that early age at natural menopause would lengthen the duration of the postmenopausal stage of life and thereby result in an earlier age at death. This study investigated the relations between age at natural menopause, duration of postmenopausal life (ie, life expectancy at menopause), and age at death (ie, age at menopause plus life expectancy at menopause). Data were derived from a study of 5,287 naturally postmenopausal Seventh-day Adventists observed during 1976-1982. Life expectancy was estimated by a mathematical model that used mortality ratios from the study and mortality rates from the US general population. For natural menopause before the age of 47 years, each one-year decrease in age at menopause was associated with a 0.53-year increase in postmenopausal life (P = .04) and a 0.47-year decrease in the age at death (P = .04). For natural menopause at the age of 47 years and older, however, each one year decrease in age at menopause was associated with a 0.99-year increase in postmenopausal life (P = .03) and only a 0.01-year decrease in the age at death (P = .85). Overall, these findings argue against the possibility that the association between age at menopause and age at death in this study was due to the relation of age at menopause to the duration of postmenopausal life. PMID- 2329250 TI - Postantibiotic colonization with Clostridium difficile in nursing home patients. AB - Clostridium difficile causes pseudomembranous colitis and is responsible for 20% to 25% of cases of postantibiotic diarrhea. In an earlier study, nursing-home patients with C. difficile infection were noted to have a high mortality rate. Because most of these infected patients had been treated with antibiotics, it was not clear whether this high mortality rate was associated with C. difficile infection or simply with antibiotic treatment. A prospective study was carried out to determine the rate of postantibiotic C. difficile colonization and risk factors for infection in patients in a 233-bed long-term care facility, as well as to determine whether C. difficile infection is associated with increased mortality. During a six-month period 150 courses of antibiotics were prescribed for 108 patients. Stool specimens were collected from 36 (33%) patients following the first course of antibiotic treatment, and 12 (33%) were infected with C. difficile. Risk factors for infection included ward location and stool incontinence. Age, body-mass index less than or equal to 18 kg/m2, and diagnoses of dementia and pressure scores tended to be associated with infection, but not significantly. Early mortality rates did not differ, but 12-month mortality for the infected patients was higher (83% vs 50%, P = .05). Therefore, we conclude that postantibiotic C. difficile infection serves as a marker of death in nursing home patients, one that can be differentiated from the risk of antibiotic treatment alone. This increased death rate may be related in part to clinically unrecognized pseudomembranous colitis or, alternatively, to absorption of C. difficile toxins or even endotoxin from the gut lumen into the systemic circulation. PMID- 2329251 TI - Occurrence of adverse effects and high amantadine concentrations with influenza prophylaxis in the nursing home. AB - Amantadine, in a dose of 100 mg/day, is recommended for influenza prevention in older nursing home residents. We studied an influenza prevention protocol in a 98 bed community nursing home (96% female; mean age = 87.4 years). Fifty-five residents received amantadine when influenza A was confirmed. Although no further influenza cases were diagnosed, 22% experienced adverse events. Dose in mg/kg/day was significantly higher in the group experiencing adverse events (2.24 +/- 0.98 vs 1.76 +/- 0.35; P less than .01). Amantadine concentrations in 32 residents ranged from 128-5,810 ng/mL. Six residents had amantadine concentrations greater than 1,000 ng/mL. Seventy-eight percent would have qualified for further dose reduction on the basis of estimated creatinine clearance. The results suggest that adverse events may be an important problem with the 100 mg/day dose, and this dose may be excessive for influenza prophylaxis in many nursing home residents. PMID- 2329252 TI - Incontinence among elderly community-dwelling dementia patients. Characteristics, management, and impact on caregivers. AB - Incontinence was identified by 36% of 184 caregivers as a problem in their care of older community-dwelling patients with dementia. Incontinent dementia patients had greater impairment of cognitive function and more frequent behavioral problems than did patients without incontinence. Burden scores were higher among caregivers of incontinent patients, but multiple regression analyses indicated that factors other than incontinence contributed more to perceived burden. Follow up interviews revealed that incontinence had played an important role in most decisions to institutionalize among caregivers of patients who were placed in a nursing home between interviews; it rarely, however, was the primary reason. The majority of incontinent patients still residing in the community were being managed by nonspecific techniques such as diapers and toileting schedules. These data emphasize the need to educate community caregivers of dementia patients in the appropriate management of incontinence and the need for further research on methods of effectively targeting assessment and treatment strategies to this patient population. PMID- 2329253 TI - Procainamide-cimetidine drug interaction in elderly male patients. AB - Thirty-six hospitalized male patients receiving oral sustained-release procainamide every six hours for the treatment of ventricular arrhythmias were studied at steady-state before and after oral cimetidine 300 mg every six hours for three days. Average age and weight were 73 +/- 12 (SD) years and 76 +/- 10 kg. Patients did not have a myocardial infarction within the last two years or congestive heart failure and had calculated creatinine clearances (CrCl) between 35 and 75 mL/min/70 kg. Ten patients had urine collections that permitted computation of the ratio between the renal clearance of procainamide and CrCl (PA/CrCl) and the renal clearance of n-acetyl-procainamide (NAPA) and CrCl (NAPA/CrCl). The average steady-state procainamide and NAPA concentrations increased 55% and 36%, respectively, during cimetidine treatment (P less than .01). Twelve patients experienced mild to severe symptoms of what may have been procainamide toxicity. Apparent procainamide oral clearance decreased 41% while patients received cimetidine (P less than .01). PA/CrCl and NAPA/CrCl ratios decreased by 33% and 21%, respectively, during cimetidine therapy (P less than .05). Cimetidine therapy given to older male patients taking procainamide can cause steady-state concentrations of procainamide to rise to toxic levels. Patients prescribed this combination should be monitored carefully for adverse side effects. PMID- 2329254 TI - Complications of the "Mayo" enema. A lesson in iatrogenic illness. PMID- 2329255 TI - Mania and a gait disorder due to cobalamin deficiency. PMID- 2329256 TI - Candidates for the Certificate of Added Qualifications in Geriatric Medicine. Who, why, and when? AB - We surveyed physicians who took the examination for certification for Added Qualifications in Geriatric Medicine, physicians who only inquired about the examination, and physicians who expressed no interest in the examination to learn about practice characteristics of those who took the examination and their reasons for taking it. Based on a 72% response rate, we were able to demonstrate that those who took the examination took care of an older population of patients and disproportionately more of the oldest-old. These physicians were more likely to report the care of older people to be a professional focus and, in internal medicine, were more likely to have had formal training in geriatrics. Their reasons for taking the examination were primarily to obtain credentials but also frequently to improve their ability to care for older people. Nearly two-thirds of those who had inquired about the exam but did not take it in 1988 plan to do so at a later date. PMID- 2329257 TI - Hypoglycemia and sepsis in two elderly diabetics. PMID- 2329258 TI - Comparison of RA 131I treatment protocols for Graves' disease. AB - The efficacy of 131I therapy in achieving euthyroidism has been studied in a group of 264 patients followed for up to 10 yr. One hundred and eighty-six were given a dose adjusted for thyroid size and radioactive iodine uptake (Protocol 1), and a second group received the same dosage followed by antithyroid drug therapy plus potassium iodide for 15 days (Protocol 2). At 10-yr follow-up, 50 60% of patients were euthyroid. 25-29% of patients required 2 doses of 131I, and 4-5% required 3 doses. Fewer patients became hypothyroid when their pretreatment FTI was above the average value. More patients became hypothyroid, if their pretreatment test for antimicrosomal antibodies was positive. Patients who required a second dose of radioactive iodide had a significantly greater chance of having worsening of their ophthalmopathy than those who became hypothyroid after the first dose. Treatment with radioactive iodide under either protocol appears to achieve euthyroidism at 10 yr with an incidence higher than that achieved by antithyroid drugs and comparable to that reported for subtotal thyroidectomy. PMID- 2329259 TI - A new approach for calcitonin determination based on target cell responsiveness. AB - We report the development and validation of three microbioassays for calcitonin based on calcitonin-induced inhibition of the activity of isolated osteoclasts. Having precisely quantified osteoclast motility, spreading and bone resorptive activity, we have applied stringent analytical procedures to define assay characteristics. We have found that the appropriately transformed responses significantly regress on log dose of the peptides. Furthermore, potency estimates obtained using calcitonins from three species (human, salmon and a synthetic analogue of eel calcitonin) have been found to be consistent with those obtained using conventional calcitonin bioassays. In addition, the assays are remarkably sensitive (detection limit 10(-15) M), highly specific and precise. We have determined plasma levels of bioactive calcitonin on samples from patients with medullary thyroid carcinoma; these are several-fold lower than those obtained using our routine calcitonin radioimmunoassay. Our study thus, forms the basis of an entirely new approach for the determination of 'biologically active' calcitonin, and we envisage that such target cell-specific assays could become useful microanalytical methods. PMID- 2329260 TI - Concentrations of somatomedin-C and triiodothyronine in patients with thyroid dysfunction and nonthyroidal illnesses. AB - We studied the possibility of an association between serum somatomedin-C (Sm-C) and thyroid hormone concentrations. For this purpose 34 hyperthyroid patients, 39 patients with primary hypothyroidism, 36 patients with severe nonthyroidal illnesses (NTI), and 63 euthyroid healthy control subjects were examined. The mean concentration of serum dialyzable free triiodothyronine (FT3) was 26.6 +/- 15.4 pmol/l (+/- SD) in hyperthyroidism, 2.8 +/- 1.2 in hypothyroidism, 4.2 +/- 1.1 in NTI, and 5.3 +/- 0.7 in controls. The lowest mean concentration of serum Sm-C (10.1 +/- 3.0 nmol/l) was found in the NTI group and the highest in the hyperthyroid group (16.8 +/- 3.2): these concentrations differed significantly from the mean control level (12.2 +/- 2.2). In NTI patients the serum FT3 and T3 levels correlated significantly with the serum Sm-C levels (r = 0.63; p less than 0.001, r = 0.65; p less than 0.001, respectively). In hypothyroid patients there was a weak correlation between the serum FT3 and Sm-C levels (r = 0.36; p less than 0.05), but no correlations were found in hyperthyroid and healthy subjects. We conclude that the lowered Sm-C levels in NTI do not reflect a hypothyroid state, as normal Sm-C levels were found in hypothyroidism, and that impaired nutritional state of the patients is the most likely explanation for the association between Sm-C and FT3 (and T3) in NTI. PMID- 2329261 TI - Acute withdrawal of short-term or prolonged L-triiodothyronine administration to thyroidectomized rats results in similar rapid increases in TSH beta mRNA. AB - In man, following the treatment of hyperthyroidism, or the withdrawal of prolonged suppressive thyroid hormone therapy, recovery from thyrotrope suppression may not occur until thyroid hormone concentrations have been subnormal for several weeks. Short-term studies in rodents have demonstrated a rapid increase in TSH synthesis after the acute withdrawal of thyroid hormones. We treated thyroidectomized rats with supraphysiologic doses of 1 triiodothyronine (T3) for 67 days, then abruptly withdrew treatment and compared the time course of thyrotrope recovery to that in animals given T3 for only 10 days. Increases in TSH beta mRNA after abruptly stopping T3 were qualitatively similar in both groups. After short-term T3 administration, TSH beta mRNA was detectable on the second day after stopping T3 administration and rose an additional 10-fold by day 5. After prolonged T3 administration, TSH beta mRNA was barely detectable on the second day after stopping T3 administration, clearly detectable on the third day, and increased an additional 20-fold by day 7. Compared to animals who received T3 for only 10 days, suppression of the thyrotrope by T3 administration for 67 days resulted in a nonsignificant delay in TSH beta mRNA synthesis of 24 h or less following the abrupt withdrawal of thyroid hormone. It is possible that differences in rat and human thyrotrope responsiveness account for the apparently different biologic behavior. PMID- 2329262 TI - Acromegaly and primary amenorrhea: ovulation and pregnancy induced by SMS 201-995 and bromocriptine. PMID- 2329263 TI - A study of pineal-prolactin interaction: prolactin response to an acute melatonin injection in patients with hyperprolactinemia. AB - Several studies demonstrated that the pineal gland plays a regulatory role in PRL secretion. At present, however, there are few clinical data only about the pineal function in PRL secretion disorders. To further clarify which is the pineal importance in the dysfunctions of PRL release, we have evaluated the effect of an acute injection of the pineal hormone melatonin in 19 patients with hyperprolactinemia, 8 of whom had idiopathic hyperprolactinemia, while the other 11 had a prolactinoma. Melatonin was given im at a dose of 20 mg at 09:00 h, and venous blood samples were collected at -20, 0, 20, 60, 120, 180 min. A normalization of PRL levels was achieved after melatonin injection in 3/8 patients with idiopathic hyperprolactinemia, while no effect was seen in patients with prolactinoma. Further studies, by evaluating the effect of a chronic treatment, will be required to define which is the action of melatonin on PRL release in PRL secretion disorders, and to evaluate its possible therapeutic role. PMID- 2329265 TI - Review and preview in 1990. PMID- 2329264 TI - Determination of IGF-II levels in human serum using the erythroleukemia cell line K562. AB - A homologous radioreceptor assay (RRA) has been developed for Insulin-like Growth Factor II (IGF II) using the human erythroleukemia cell line K562. These cells have binding sites for insulin and IGF-II but not for Insulin-like Growth Factor I (IGF I). All samples were dissociated and separated from binding proteins by gel filtration at acidic pH. In healthy adults the mean serum level of radioreceptor assayable IGF II (RRA-IGF II) and 95% confidence limits were 965 ng/ml and 717-1299 ng/ml, respectively. The mean level in GH deficient patients was significantly lower (p less than 0.001) compared with healthy subjects whereas no change was found in patients with acromegaly and uremia. Slightly lowered levels of RRA-IGF II were found in one patient with a tumor induced hypoglycemia. PMID- 2329266 TI - Humanity in intensive care. PMID- 2329267 TI - Acute meningococcaemia: a case study. AB - A 20-year-old female presented with sudden onset of abdominal pain, diarrhoea and vomiting progressing to fever, tachycardia and mild hypotension. Within 12 hours, a petechial rash appeared on the face and abdomen, spreading to the extremities. Laboratory findings confirmed the diagnosis of acute meningococcaemia. Clinical features of endotoxic shock, vasculitis and skin necrosis rapidly ensued. Aggressive treatment to control the septicaemia, disseminated intravascular coagulation and unstable cardiovascular state ultimately proved successful. Approximately 6 weeks later, amputation of some of the digits and extensive skin grafting were carried out in the Regional Burns Unit. However, serious psychological side effects gradually began to appear which required urgent psychiatric intervention. For an active young woman the challenge of coping with such a severe illness and coming to terms with the disability and disfigurement resulting from it was almost overwhelming. It was, perhaps, particularly hard because of the threat posed to her ambition to complete her nursing education and become a nurse. Little was found in the nursing literature on acute meningococcaemia. But this illness provides considerable challenges not only to those who suffer from it, but also to those who nurse them. A final brief review of published literature on acute meningococcaemia and the clinical manifestations and outcome of it is provided for those who wish to know more about it. PMID- 2329268 TI - Needs of family members of critically ill patients--a Northern Ireland perspective. PMID- 2329269 TI - Autologous blood transfusion (ABT). A study of the clinical applications and a literature review. PMID- 2329270 TI - Educational aspects of cardiopulmonary resuscitation (CPR) training. AB - The knowledge and skills surrounding the practice of cardiopulmonary resuscitation (CPR) have become essential to intensive care nurses and to nurses in general. With formalized training and refresher courses becoming more common in this country, it is evident that after relatively short periods of time the knowledge and skills acquired at such courses may be lost. While much consideration has been given to the content of both Basic and Advanced Cardiac Life Support (BCLS and ACLS) courses, relatively little attention has been paid to the educational issues surrounding CPR training. This paper explores some of these issues from the perspective of adult learning (andragogy). Research is cited from a wide range of sources to illustrate that CPR skill and knowledge deterioration is not unique to nursing, and that educational techniques exist which may improve current educational practices. PMID- 2329271 TI - A description of stressors and coping strategies among parents of critically ill children--a preliminary study. AB - The purpose of this preliminary study was to describe (1) perceived stressors and (2) coping strategies among parents of critically ill children. Stress and coping within this population has been subjected to little research. The research that has been reported is predominantly quantitative. The validity of this research is unclear. Five parents of children in a pediatric intensive care unit (PICU) setting were interviewed. They were asked to describe the principal sources of stress (stressors) they encountered and how they dealt with these (coping strategies). The interviews were content analysed. Five categories of stressors were identified. These included parental role conflict, concern for child, environment, friends, and child's siblings. Five categories of coping strategies were identified. These included things you think about, actions directed toward other people, drawing on support from others, things you do, and things you draw on from the environment. The findings of this study have highlighted deficiencies within the existing literature on stress and coping within this population. There is a need for further qualitative research in this area. This will foster the development of a better understanding of the experience of parents for caregivers and provide a foundation for further research. PMID- 2329272 TI - Communication between nurses and post-anaesthetic patients. AB - This paper explores the verbal and non-verbal communication between nurses and post-anaesthetic patients in the recovery unit of an inner London hospital. Although the patients had only minor operations the study findings and the method of conversation analysis provide ideas which could have wider relevance in intensive care. A video camera was used to record nurses' conversations with dental patients recovering from their operations. The resultant tape was studied for the utterances and body movement used by the nurses in order to engage the patient in conversation. Analysis indicated that the nurses were skilled communicators who took into account the patients' low level of consciousness and lack of physical orientation when initiating and maintaining interaction. This is an important factor in the care of post-anaesthetic patients, as the recovery nurse may need to gain the patient's attention to converse with him for a variety of reasons, including safety and the need to orientate the patient to his environment in order to reduce anxiety (Mallett, 1986). The ability of the nurse to communicate successfully is, therefore, one of the prerequisites for adequate nursing care in the Recovery Unit. In addition, the notion of therapeutic communication as a separate entity to skillful conversation is raised. PMID- 2329273 TI - Effect of cyclosporin A on the ontogeny of different T cell sublineages in chickens. AB - We have used a panel of murine mAb against chicken TCR and associated molecules to study the effect of cyclosporin A (CsA) on the ontogeny of the different sublineages of T cells. After injection of CsA (20 mg/kg/day from day 0 to 20) we observed a significant suppression of the normal maturation of the TCR2 (alpha beta TCR) cells in their transition from cortical CD4+CD8+ thymocytes to the mature single positive cells in the thymus medulla. The TCR3 subpopulation, a distinct form of alpha beta-like TCR in chickens, was inhibited from initially developing within the cortex by CsA, indicating that the TCR3 subpopulation is functionally distinct from the TCR2+ cells. In contrast, the maturation and peripheral emigration of TCR1 (gamma delta TCR) cells was unaffected by CsA treatment. Mature splenic T cells sorted for either TCR1+ or TCR2+ subsets were equally sensitive to CsA blockade of Con A-stimulated mitogenesis, indicating that there is no inherent difference in CsA sensitivity between these sublineages. Furthermore, no difference was detected in the expression of class II MHC Ag in thymi of birds treated with olive oil vs CsA. Inasmuch as the mechanism of CsA action appears to involve inhibition of TCR initiated signal transduction for lymphokine synthesis, these data indicate that a similar signaling is involved in thymic repertoire selection for TCR2. The lack of an effect on TCR1 cell maturation suggests that the TCR1 repertoire may not undergo selection in the thymus as do TCR2+ cells. PMID- 2329274 TI - An absence of T cells in murine bone marrow allografts leads to an increased susceptibility to rejection by natural killer cells and T cells. AB - The mechanisms behind the increased incidence of marrow graft failure in recipients that receive allogeneic marrow depleted of T cells were studied. Recipient mice were lethally irradiated and challenged with bone marrow cells (BMC) from C.B-17 +/+ (+/+) donors. Radioisotope 125IUdR incorporation was assessed 5 to 7 days after transfer to determine the extent of engraftment. Some groups received BMC in which the T cells were removed by treatment with antibody and C. In addition, some groups received BMC from T cell-deficient C.B-17 scid/scid (SCID) mice to determine the postulated need for donor T cells in hematopoiesis and engraftment. In a model system that distinguishes between possible host NK cell and radioresistant T cell-mediated rejection of marrow allografts, it was determined that the absence of donor T cells in a marrow graft does not affect engraftment in syngeneic recipients. However, both host NK cell and radioresistant T cell rejection was markedly enhanced when SCID BMC or BMC from C.B-17 +/+ donors that had T cells removed by antibody and complement were infused into irradiated allogeneic recipients. Furthermore, the addition of alloreactive thymocytes as a source of T cells could abrogate this increased susceptibility of the BMC to host rejection mechanisms. As determined by histology and 59Fe uptake, the addition of thymocytes resulted in enhanced erythropoiesis. These results suggest that the increased incidence of marrow graft failure when BMC depleted of T cells are used is a result of active rejection by host effector cells and that the adverse effect of marrow T cell depletion can be reversed by the addition of thymocytes. PMID- 2329275 TI - Alterations in antibody-dependent cellular cytotoxicity during the course of HIV 1 infection. Humoral and cellular defects. AB - HIV-1-specific cell-mediated cytotoxicity (CMC) is a form of antibody-dependent cellular cytotoxicity (ADCC) in which HIV-1-specific antibodies arm NK cells directly to become cytotoxic for targets bearing HIV-1 antigenic determinants. This non-MHC-restricted cytotoxic activity is present in early stages of disease and declines markedly with disease progression. To understand the cellular and humoral factors contributing to the reduction in this activity, the conditions under which maximal arming of cells occurs was examined in vitro. With the use of a large patient cohort, a strong positive correlation was found between the capacity of a serum to direct lysis in standard ADCC assays and its ability to arm NK cells. Patients with minimal HIV-1-specific ADCC-directing antibodies exhibited low levels of CMC and were unable to arm normal effector cells in vitro. The lack of sufficient ADCC-directing antibodies was found to be one cause of defective CMC in some patients. Unlike asymptomatics, only a weak positive correlation was found between arming and ADCC with sera from AIDS patients, indicating that a factor other than absolute HIV-1 specific antibody titer was responsible for decreased CMC in this patient population. Another group of patients was found to have diminished CMC despite the presence of antibodies in the serum that were fully capable of arming normal effector cells to become cytotoxic for gp120-expressing targets. When compared with those of normal individuals, lymphocytes from seropositive patients mediated significantly reduced levels of cytotoxicity in ADCC and arming assays with the use of a high titered HIV-1-specific serum. In both assay systems, the magnitude and frequency of dysfunction in antibody-dependent cytolysis was found to be greater among AIDS patients than among asymptomatic individuals. The demonstration of both cellular and humoral defects in the ability of seropositive individuals to manifest ADCC reactivities strongly suggests that HIV-1 infection may significantly compromise the effectiveness of this potentially important cytolytic reactivity in vivo. PMID- 2329276 TI - Transforming growth factor-beta 1 is a costimulator for IgA production. AB - Transforming growth factor-beta 1 (TGF-beta 1) belongs to a family of polypeptides involved in the regulation of cell growth and differentiation. We have examined the ability of TGF-beta 1 to regulate isotype specific Ig secretion by murine spleen B cells. TGF-beta 1, in the presence of rIL-2, induced a synergistic 10-fold or greater increase in IgA secretion by LPS-stimulated spleen B cells. TGF-beta 1 alone had little to no effect on IgA secretion. In contrast, TGF-beta 1, with or without rIL-2, markedly inhibited IgG1 and IgM secretion under the same conditions. The costimulatory activity of TGF-beta 1 and rIL-2 on IgA secretion was seen in cultures of surface IgA negative B cells and was inhibited by anti-TGF-beta 1 antibody in a dose dependent manner. Vicia villosa agglutinin non-adherent Peyer's patch T cells, which secrete IL-2, also synergized with TGF-beta 1 and could substitute for the activity of LPS and rIL-2 on the IgA response. Finally, IL-5 added after 2 days of culture, but not at the beginning of culture, synergized with TGF-beta 1 on the IgA response. These studies indicate that TGF-beta 1 can interact with other lymphokines and selectively modulate the IgA response. PMID- 2329277 TI - Production of tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) by murine pre-B and B cell lymphomas. AB - Media from murine pre-B and B lymphoma cell cultures, but not from myeloma cell cultures, was cytotoxic to WEHI 164 cells, causing these TNF-sensitive targets to release 51Cr. The cytotoxic activity in the culture medium reached maximum levels approximately 4 days after the cell culture was initiated. The constitutive production of the factors was not influenced by depletion of serum from the medium or by the addition of either phorbol ester or bacterial endotoxin. The factor has a Mr greater than 10 kDa, and its cytotoxicity was abolished by anti serum against murine TNF. Northern blot analysis with the use of cDNA probes to murine tumor necrosis factor (TNF-alpha) and lymphotoxin (LT, TNF-beta) showed high levels of TNF-mRNA in the pre-B cell lines, lower levels in the mature B cell lines and no TNF-mRNA in the myeloma cell lines. LT mRNA was present in pre B cell lines, at a much lower concentration in only one of the B cell lines, and was not present in three other B lymphomas or in the myelomas tested. The results show a positive correlation between the presence of TNF and/or LT mRNA and the 51Cr-releasing activity present in the cell culture medium. Our data indicate that TNF and LT can be produced by murine B cells and that the synthesis of these cytokines may be restricted to certain differentiation stages of the B cell lineage. PMID- 2329278 TI - IL-4 blocks the up-regulation of IL-2 receptors induced by IL-2 in normal human B cells. AB - A negative influence of IL-4 on the IL-2-induced B cell proliferation and differentiation has recently been reported. In this study, we have further investigated a role of IL-4 on human tonsillar B cell proliferation and IL-2R expression. IL-4 enhanced Staphylococcus aureus Cowan 1 strain (SAC)-induced B cell proliferation, reaching the peak on day 3. However, from day 4, IL-4 inhibited IL-2-induced proliferation. In the cross-linking study, IL-4 enhanced the density of 125I-IL-2-binding protein at low affinity binding condition (2 nM of 125I-IL-2) in SAC-activated B cells. However, IL-4 blocked the enhancement in the density of 125I-IL-2-binding proteins induced by IL-2, from day 3, in both high (50 pM of 125I-IL-2) and low affinity binding conditions, suggesting that IL 4 is able to block IL-2-induced IL-2R up-regulation. This was confirmed by a binding study: B cells that cultured for 3 days with SAC plus IL-2 expressed an average of 180 +/- 20 high affinity receptors/cell with a Kd of 12 pM and 5800 +/ 500 low affinity receptors/cell with a Kd of 980 pM. By coculturing with IL-4, high affinity receptors were almost undetectable and the expression of low affinity receptors was reduced by more than 80%. IL-4-mediated inhibition of IL-2 induced IL-2R expression does not seem to be due to the direct interaction between IL-4 and cell surface receptors, inasmuch as preincubation of cells with IL-4 for 60 min at 37 degrees C did not alter the binding of 125I-IL-2 to cells previously cultured for 3 days with SAC plus IL-2. These data suggest that IL-4 has a capacity to block the up-regulation of the high as well as low affinity IL 2R-induced by IL-2 in normal human B cells, and could provide a possible explanation for the decreased responsiveness of B cells to IL-2 in the presence of IL-4. PMID- 2329279 TI - The location of binding sites on C1q for DNA. AB - Previous studies have suggested that C1q reacts with DNA via both the globular region of C1q (GR) and the collagen-like region of C1q (CLR). In this study, the binding of dsDNA and ssDNA to GR and CLR was quantitated by a solid-phase assay. Both dsDNA and ssDNA bound to the GR and CLR of C1q in an ionic strength dependent manner. Under physiologic salt concentrations, however, dsDNA and ssDNA bound preferentially to CLR and not to GR. The binding of dsDNA to C1q was not affected by heat inactivation of C1q or its exposure to pH 4.45, which abolished the binding of heat-aggregated human IgG (AHG) with C1q. The preincubation of the solid-phase C1q with AHG did not decrease the binding of dsDNA or ssDNA to the solid-phase C1q. These results indicate that the major sites for binding DNA to C1q are located in the CLR of C1q and are not overlapping with those for AHG or immune complexes. PMID- 2329280 TI - Selective activation of human monocytes by the platelet-activating factor analog 1-O-hexadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine. AB - The capacity of platelet-activating factor (PAF) and its 2-O-methyl analog (methoxy-PAF) to activate human monocytes, neutrophils and platelets were compared. Both PAF and methoxy-PAF increased monocyte cytotoxicity toward WEHI 164 cells with a maximal increase in cell killing at 100 pM to 1 nM. Methoxy-PAF was slightly, but significantly, more potent than PAF for increasing cytotoxicity. PAF and methoxy-PAF increased monocyte release of TNF two- to three fold above control release with no difference in their potency. Methoxy-PAF increased cell-associated TNF maximally after 2 to 3 h of incubation and increased TNF release maximally after 5 to 18 h of incubation. PAF induced release of the neutrophil granule enzyme beta-glucuronidase with maximal net release of 15 to 20% at 100 nM PAF whereas methoxy-PAF did not induce release of beta-glucuronidase. Similarly, 10 nM PAF induced 30% platelet aggregation whereas methoxy-PAF induced aggregation only at 1000-fold higher concentrations. Analysis of PAF and methoxy-PAF metabolism by monocyte and serum acylhydrolases indicates that methoxy-PAF is substantially more resistant than PAF to degradation by these enzymes. These observations indicate that methoxy-PAF activates monocytes selectively and suggest that this phospholipid or a related compound could be used for in vivo immunotherapy. PMID- 2329281 TI - Murine susceptibility to street rabies virus is unrelated to induction of host lymphoid depletion. AB - The mechanism and cellular targets of mononuclear cell depletion were investigated in strains of mice susceptible or resistant to lethal infection with a virulent street rabies virus (SRV). Significant depletion was evident in the thymus of all infected animals at approximately 5 days postinfection and subsequently involved the spleen and lymph nodes in mice developing clinical signs of rabies. Immunofluorescent analyses of lymphocyte subsets in depleted spleens revealed that cell losses were non-selective since the relative proportions of K+, Thy-1+, Lyt-1+, and Lyt-2+ cells remained unchanged. Diminished expression of I-A membrane glycoproteins on spleen lymphocytes was noted, however, perhaps reflecting reduced availability of I-A-inducing lymphokines. Adrenal hormone toxicity was identified as the cause of mononuclear cell depletion in that mice adrenalectomized before SRV infection showed no evidence of lymphoid depletion. The failure of adrenalectomy to alter anti-rabies antibody responses or SRV lethality also indicates that involution of the lymphoid system is a consequence and not a cause of genetically controlled host susceptibility to SRV. The mechanism of adrenal gland stimulation in rabies infected mice appears to involve a virus-induced dysfunction in the pituitary gland rather than a stress response to paralysis-induced starvation, based on results of kinetic studies on weight loss, appetite depression, and paralysis in these animals and previous reports of pituitary infection during rabies disease. The relationship of these observations to current theories on rabies virus pathogenicity is discussed. PMID- 2329282 TI - Characterization of the human and murine IL-7 genes. AB - IL-7 cDNA clones were used to isolate clones from the human IL-7 gene locus. Characterization of the clones revealed that the human IL-7 gene contains six exons, distributed over more than 33-kbp. An 18 amino acid insert found in human IL-7, for which no counterpart has yet been demonstrated in murine IL-7, is exactly encoded by exon 5 of the human gene. Clones were also isolated containing 5' flanking sequences and the first four exons of the murine IL-7 gene. RNase protection studies of murine IL-7 mRNA, as well as the sequences of 5'-terminal murine IL-7 cDNA clones obtained by anchored polymerase chain reaction cloning, indicate that the murine IL-7 gene initiates transcription at multiple sites within a 200-bp region. This region, and the sequence upstream of this region, appears to lack transcriptional regulatory sequences commonly found in eukaryotic promoters, including the TATA and CAAT sequences. However, the region lies within a CpG island, and contains potential recognition sequences for the "helix-loop helix" class of DNA binding proteins. PMID- 2329283 TI - HLA-AR, an inactivated antigen-presenting locus related to HLA-A. Implications for the evolution of the MHC. AB - The MHC contains many class I genes other than those known to present peptides to T lymphocytes. These additional class I genes vary between species and their functions are unknown. Genes involved in Ag presentation, HLA-A,B,C in humans, are highly diverse whereas other class I genes are of much more limited diversity. We have studied alleles of a gene, HLA-AR, that is closely linked and structurally related to HLA-A; properties consistent with these two loci having been formed by a gene duplication. Compared to HLA-A the diversity in HLA-AR is much less, and does not focus on residues of a putative Ag recognition site. However, the structure of HLA-AR alleles closely resembles those encoding Ag presenting molecules, although the presence of one or two deleterious mutations prevents these alleles being active in Ag presentation. These results suggest HLA AR derives from an Ag-presenting locus that became inactivated, possibly as a result of positive natural selection due to changing demands on T cell immunity. Thus absence of diversity may sometimes correlate with loss rather than preservation of function in class I MHC genes. PMID- 2329284 TI - [Long-term follow-up of tetralogy of Fallot corrected by Okamura's method under simple deep hypothermia]. AB - Corrective surgeries for TOF (Tetralogy of Fallot) were performed in 350 patients from 1967 to 1983 by Okamura's method under simple deep hypothermia. Radical operations were done in all patients, including very young children. The operative techniques had several differences from the standard procedure. Patients were operated on without any extracorporeal perfusion, the VSD was closed by a patch which was attached firmly to the margin of VSD using cross mattress sutures and the right ventricular outflow tract was dilated by infundibular myectomy only, with no use of outflow-patch-plasty. One hundred ten out of 350 patients were investigated by questionnaire and their responses showed that they had few long-term problems. ECG, X-ray, echocardiography and stress test by treadmill were performed in 26 cases. They were divided into two groups by the presence or absence of pulmonary regurgitation (PR). The CTR of the PR (+) group was larger than the PR (-) group (p less than 0.05). There was no statistical difference in cardiac function between the two groups. Few arrhythmias were observed during the exercise test. No residual shunts were found in any of the cases. The occurrence of PR was relatively rare in those who were operated on before their second birthdays. These results suggest that our surgical techniques under simple deep hypothermia are adequate to correct TOF. PMID- 2329285 TI - [Changes in the immune response in postoperative patients while running the ventricular assist device (VAD)]. AB - We examined the immunological parameters in two patients who were assisted with LVAD in postoperative LOS. Both patients demonstrated transient consumption of complements immediately after running the LVAD. The serum concentrations of immunoglobulins (IgG, IgM, IgA) showed no significant decrease. Both patients had significant postoperative lymphopenia, but recovered in a week. A decrease in the number of T cells was observed in both patients. The OKT4/OKT8 ratio initially increased in one patient, but gradually declined postoperatively. In the other patient, the OKT4/OKT8 ratio decreased. The lymphocyte response to mitogen (PHA) remained significantly depressed when the number of lymphocytes returned to the normal level, suggesting that the lymphocytes were functionally impaired. Such findings are generally observed after cardiac surgery. Thus, LVAD does not affect the immune response. PMID- 2329286 TI - [Valve prostheses of mitral position in children]. AB - Twenty children less than 15 years old of age who had undergone mitral (left sided atrioventricular) valve replacement before August 1983 have been followed up until October 1988. Fourteen biological valves (B-group) and seventeen mechanical valves (M-group) were used in them. Preoperative conditions had been similar between B- and M-groups. For the B-group, there were one operative death and two late deaths. For the M-group there were no operative death and three late deaths. An actuarial survival rate at ten years was 53.5 +/- 23.3% for the B group and 85.7 +/- 9.4% for the M-group (not significant). All biological valves were calcified and failed in 27 to 89 months. Three mechanical valves caused thrombosis. There was no other complication for both groups. An event free rate was 0% at eight years for the B-group, however it was 70.6 +/- 11.0% at ten years for the M-group (p less than 0.025). Our data indicates that the mechanical valve is more suitable than the biological valve for children. PMID- 2329287 TI - [Oxygen uptake during exercise before and after cardiac valve surgery: anaerobic threshold and maximal oxygen uptake]. AB - Exercise stress tests with bicycle ergometer were performed before and after surgery in 14 patients with valvular heart diseases. Aortic valve replacements were performed in two patients, open mitral commissurotomy in two, mitral valve replacement in eight and combined valvular procedure in two. All patients except one showed improved NYHA function class after the surgery. Oxygen uptake was assessed at anaerobic threshold and peak achieved workload. One patients who failed to increase his heart rates during exercise both before and after surgery revealed unchanged NYHA function class and decreased oxygen uptake postoperatively. The other patients showed statistically significant increases of oxygen uptake not only at anaerobic threshold but also at peak achieved workload. At anaerobic threshold, oxygen uptake was 0.92 + 0.14 l/min before surgery and 1.09 + 0.22 l/min after surgery. Maximal oxygen uptake increased from 1.11 + 0.27 l/min to 1.47 + 0.36 l/min postoperatively. Heart rates at anaerobic threshold and at peak workload showed no significant differences. Postoperative increases of oxygen uptake was achieved by the increases of oxygen pulses, which was considered to be from the increases of stroke volumes. PMID- 2329288 TI - [A case of accidental pneumatic rupture of the esophagus]. AB - A case of pneumatic esophageal rupture secondary to distension from compressed air was reported. The patient, a 69-year-old man who was repairing an automobile tire suddenly exploded. The blast was directed into the open mouth. He was admitted to our hospital 12 hours after the onset with the complaint of chest pain and dyspnea. Subcutaneous emphysema was seen in the neck. The chest roentgenogram revealed a partial right hydropneumothorax. The diagnosis of esophageal rupture was established by Gastrographin swallowing study. Operation was performed 46 hours after the onset. Primary closure of the middle thoracic esophagus was judged to be impossible because of a 6 cm longitudinal laceration with contaminated pyothorax. Thereafter, total esophagectomy was indicated. Esophageal reconstruction using the pediculated gastric tube was performed throughout the retrosternal route. The leakage of esophagogastrostomy in the cervical area occurred in early postoperative stage. Re-esophagogastrostomy was successfully carried out 6 weeks after the first surgery. He is uneventful 6 months after the operation. We have not found any reports of surgical cases with pneumatic esophageal rupture treated by this approach in the literature. PMID- 2329289 TI - [A case of coronary artery bypass grafting using bilateral mammary arteries in a patient with systemic lupus erythematosus]. AB - A 40-year-old female who had been treated with steroid for 10 years because of systemic lupus erythematosus (SLE) was admitted to our department for triple vessel disease with LMT lesion. She underwent bilateral internal mammary artery grafting to the right ventricular branch of RCA and the No. 7 segment of LAD. Intraoperative free flow was 70 ml/min in both bypass grafts. She dropped to severe shock with a high fever of 40 degrees C and decreased the white blood cell count of 900/mm3 on the 6th postoperative day. These clinical and laboratory findings were suggestive of rebound phenomenon of SLE or withdrawal syndrome of steroid therapy. She was treated with pulse therapy of methyl-prednisolone and her condition improved in two weeks. Histological findings of the right internal mammary artery revealed stenotic lesion of about 50%, but on June 24, 1988, postoperative angiography showed a good patency of both internal mammary arteries. Only a few reports of successful attempt of coronary artery bypass grafting for coronary lesion due to SLE are available in the literature. Some important problems concerning the surgical treatment as well as the therapy of steroid involved in this case were discussed. PMID- 2329290 TI - [A case of thoracic neurilemoma with neurilemomas of the upper limb and sacrum]. AB - A 64-year-old male was admitted in February 24, 1988 because of an abnormal shadow on chest X-ray. The tumor in the thoracic wall was removed at the thoracotomy and histology showed neurilemoma. Aspiration biopsy of tumors on the left upper limb and sacrum revealed the typical histopathologic appearance of neurilemomas. The possibility of malignant transformation and sequential appearance of tumors in patients with a neurilemoma indicates that complete resection and thorough follow-up examination are important. PMID- 2329291 TI - [A surgical case of Hodgkin's lymphoma originated from thymus]. AB - We experienced a surgical case of large Hodgkin's lymphoma of the thymus. An 18 year-old male who had been complaining of a persistent cough was admitted to our hospital. Chest X-ray film showed an anterosuperior mediastinal tumor. But there was no superficial lymphadenopathy and hepatosplenomegaly. He received a surgical extirpation of the tumor approached by median sternotomy. The tumor expanded to the whole antero superior mediastinal region, which was 18.5 X 15 X 5.5 cm in size, surrounding the trachea and main branch of aortic arch and veins. The tumor directly invaded the bilateral pleura and left innominate vein, so these regions were resected with the tumor. The left innominate vein was reconstructed with a PTFE graft. The pathological diagnosis was Hodgkin's lymphoma nodular sclerosis type by LSG classification. A post operative course was uneventful. PMID- 2329292 TI - [Surgical treatment of ventricular tachycardia after radical correction of tetralogy of Fallot]. AB - The patient was 21 year-old male with recurrent sustained VT following complete repair of tetralogy of Fallot. He underwent complete repair of tetralogy of Fallot at the age of 3. Eight years after the operation, he first noted episode of tachycardia. Sustained VT was first documented 15 years after operation, and he required direct-current cardioversion for this tachycardia. Because of life threatening arrhythmia he was transferred to our hospital for surgical management. Sustained VT was induced and found to originate from the inflow septal and outflow area of right ventricle. During the operation only right outflow type tachycardia could be induced by programmed stimulation. Diastolic fractionated local electrical activity, which suggested a reentrant circuit, was recorded at the outflow epicardial area. The outflow muscle (2 X 2 cm) showing the earliest excitation during VT was excised with cryocoagulation at the outflow tract. The resected area was closed with a Gore-Tex patch using continuous sutures. Another cryocoagulation was applied to the inflow-septal area prophylactically. After surgery, a so-called non-clinical VT was inducible, however this VT could be prevented by antiarrhythmic drugs. No spontaneous episodes of VT have been postoperatively observed for 2 months. PMID- 2329293 TI - [A successful surgical repair of anomalous right pulmonary venous connection with Goldenhar syndrome]. AB - A ten-year-old girl with Goldenhar syndrome underwent intracardial repair for partial anomalous right pulmonary venous connection into the superior vena cava. In surgical procedure the proximal tract of superior vena cava was reconstructed into double floor, low floor was tract for anomalous pulmonary venous blood drained into left atrium through the atrial septal defect which was made with resection of prinum septum, upper floor was a real tract for superior venous blood. After operation, arrhythmia did not detect. One month after operation, no stenosis along the superior vena cava or right pulmonary vein were evidenced in catheterization. This surgical technique is superior to using baffle for preventing thrombogenesis. The result suggested that this surgical technique is preferable to the reconstruction of baffle in superior vena cava. PMID- 2329294 TI - [Free arterial graft in coronary artery bypass surgery]. AB - Free arterial graft of the internal mammary artery (IMA) and the gastroepiploic artery (GEA) has been utilized for coronary artery bypass grafting in 10 patients during 44 months period. There were 6 males and 4 females and age ranged 42 to 73 year old with the mean of 60.8 year old. Eight IMA and 2 GEA were used as a free graft. Sites of distal anastomosis of the free graft were 3 at anterior descending arteries, 3 at diagonal branches and 4 at circumflex arteries. Sites of proximal anastomosis of those grafts were ascending aorta in one, concomitantly utilized saphenous vein graft in 5 and in situ IMA graft in 4 patients. Mean number of grafts was 2.9 (2-5) and mean aortic cross clamp time was 56.2 minutes (16-90 minutes). There was neither operative death, nor perioperative myocardial infarction and intra-aortic balloon pumping was not required. Postoperative angiography was made in 9 patients within 3 postoperative months. Eight (89%) free arterial grafts were patent. Relief of angina was obtained in all patients. We concluded that the complete revascularization with only arterial graft can be achieved more widely by utilizing the free arterial graft with an acceptable patency. PMID- 2329295 TI - [An operated case of atresia of aortic arch without PDDT in an adult]. AB - Atresia of aortic arch (AAA) is very rare congenital anomaly and hemodynamically comparable with interruption of aortic arch (IAA). In general it is associated with pulmonary-ductus descending aorta trunk (PDDT) and its prognosis is extremely poor. 38-year old man complained of easy fatigability and hypertension on bilateral arms. Aortography showed interruption of blood stream at aortic isthmus and rich collateral blood flow to descending aorta. PDDT or intracardiac anomaly was not found. He was diagnosed IAA, type A of Celoria-Patton without PDDT. Alternatively echocardiography and magnetic resonance imaging revealed the anatomical continuity between the aortic arch and the descending aorta. Therefore he was finally diagnosed aortic arch atresia without PDDT. The prosthetic bypass grafting was performed between left subclavian artery and descending aorta. PMID- 2329296 TI - [A case of systemic origin of an aberrant artery to the basal segments of the left lung]. AB - A thirteen-year-old asymptomatic boy was referred to our hospital because of a cardiac murmur detected on a routine physical examination at school. A plane chest radiography showed increased vascular markings in the left lower field. An Aortogram revealed a large artery arising from the descending aorta and suppling the left posterior basal segment which had no pulmonary arteries. A bronchogram showed no abnormal findings in the bronchial tree. A clinical diagnosis of systemic origin of an aberrant artery to the basal segments of the left lung was made, and left lower lobectomy was performed successfully. We discussed the difference of this anomaly from pulmonary sequestration as well as the surgical procedure. PMID- 2329297 TI - [Coronary artery disease and the results of coronary bypass surgery in diabetics]. AB - To evaluate the influence of diabetes mellitus on coronary artery disease and the results of coronary bypass surgery, a review was made of 63 consecutive patients undergoing isolated saphenous vein aortocoronary bypass, of whom 38 patients (G 1) were nondiabetic, 9 patients (G-2) had impaired glucose tolerance, and 16 patients (G-3) were diabetic. The severity of coronary artery disease was assessed using an angiographic grading system. Among three patient groups, there was no difference in total coronary score per patient reflecting total extent of disease (G-1; 15.7 +/- 5.5, G-2; 14.1 +/- 5.9, G-3; 17.1 +/- 6.3, mean +/- S.D.) and the incidence of diffusely diseased vessels. The mean number of diseased vessels (greater than 50% stenosis) per patient was 2.5 +/- 0.6 in G-1, 2.6 +/- 0.7 in G-2, and 2.5 +/- 0.7 in G-3, and the mean number of bypass grafts per patient was 2.3 +/- 0.9, 2.2 +/- 0.9, and 2.1 +/- 0.7, respectively. Coronary luminal diameters and the severity of atherosclerotic changes of coronary arteries at the site of graft anastomosis, studied intraoperatively, were similar in all groups. Vein graft blood flows and early graft patency in diabetics (112 +/- 55 ml/min, 96.9%, respectively) were also similarly good as those in the other groups (98 +/- 49 ml/min, 91.4% in G-1, and 92 +/- 39 ml/min, 94.1% in G 2). Overall hospital mortality was 1.6% (one of 63). The only death from meningoencephalitis occurred in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329298 TI - [Resection of chondrosarcoma of anterior chest wall with pleural dissemination]. AB - A 52-year-old woman admitted with difficulty of breathing and had an anterior chest wall tumor. Primary lesion of the chest wall tumor invading the inferior one third of sternum, right third to sixth ribs, a part of the right middle lobe, the pericardium and a part of the diaphragma and small nodules on the parietal pleura were resected, and a diagnosis of chondrosarcoma of the right fifth or sixth rib and pleural dissemination of the tumor was established. The defect of pericardium was repaired with artificial dura mater and the defect of bony chest wall was repaired with a double layer of Marlex mesh. Although the resection was palliative because of pleural dissemination, she is now working as a housewife without difficulty of breathing. PMID- 2329299 TI - [Successful re-reconstruction for complete disruption of the right main bronchus by blunt chest trauma]. AB - A 22 year-old man was brought to our hospital about twenty-three minutes following a high-speed motorbicycle accident in which he had blunt chest trauma. He was in severe respiratory distress with marked dyspnea and restless with extensive subcutaneous emphysema involving anterior chest wall, cervical and bilateral inguinal regions. A chest X-ray revealed bilateral pneumothorax involving mediastinal emphysema and also fracture of right submandibular and clavicula. In spite of orotracheal intubation and insertion of bilateral chest tube, continuous air leak and pneumothorax did not improve. Bronchoscopy revealed the disruption of mucosa of the right main bronchus at the bifurcation. Emergency right thoracotomy was performed and there was the complete disruption of the right main bronchus. Anastomosis of the right main bronchus with circumferential resection was undertaken on May 30, 1987 about two hours after trauma. About three months after reconstruction, bronchoscopic examination revealed stomal stenosis with deformation of tracheobronchial cartilage and granulation. The stenosis showed severe irregularity by deformed cartilage and thickened scar, so widening by Nd-YAG laser vaporization was inadequate in effect. Seven months after first reconstruction, we performed re-reconstructive operation, right upper sleeve lobectomy with partial resection of carcina and right wall of trachea for scar with severe deformation of cartilage. Following the operation, the patient suffered from sepsis with pneumonitis accompanied by lung edema. This complication was treated successfully. We considered that acute pneumonitis was caused by reventilation with increase of perfusion after tracheobronchial reconstruction. Consequently, we thought it important to treat such patients with long term IPPB postoperatively with adequate medication for respiratory system. PMID- 2329300 TI - [A case of mitral regurgitation caused by necrosis and total rupture of the papillary muscle]. AB - Mitral regurgitation (MR) caused by total rupture of the papillary muscle has so ominous prognosis that it is treated by surgery exceedingly rarely. We recently experienced a case of MR caused by total rupture of the posterior papillary muscle that had presumably occurred after myocardial infarction. The patient was a 52-year-old male who was admitted to a hospital with liver dysfunction where he was noticed for the first time of his having cardiac murmurs and was diagnosed as having MR on the basis of echocardiography. With this diagnosis he was transferred to our department. Examination on admission revealed the patient to have an NYHA class III mitral incompetence with ECG evidence of old posteroinferior myocardial infarction. Cardiac catheterization demonstrated total occlusion of the segment 1 of the right coronary artery and MR, Sellers III. Abnormal echoes were noted in the left ventricle that moved almost synchronously with the posterior leaflet of the mitral valve, a finding leading to a suspected diagnosis of rupture of the posterior papillary muscle or chordae tendineae. Intraoperative findings were confirmative of total rupture of the posterior papillary muscle and mitral valve replacement was performed using a SJM prosthetic valve. Histological examination of the ruptured muscle revealed presence of necrosis, but no other specific inflammatory changes. Documented cases of surgically treated total papillary muscle rupture are quite limited in number, the present case being the 4th to be reported in Japan. PMID- 2329301 TI - [Effect of nicardipine hydrochloride on myocardial protection in "in situ isolated dog heart"]. AB - This study was undertaken to determine the effect of nicardipine hydrochloride on myocardial protection in "In situ isolated dog heart". To assess the myocardial function, recovery of the left ventricular function, myocardial water content and myocardial ultrastructure were evaluated before 90-minute cardiac arrest and after 60-minute reperfusion. Isovolemic left ventricular function was evaluated with an intraventricular balloon method (balloon volume, 5-20 ml) using a preparation of "In situ isolated dog heart". The spontaneous cardiac beat after 90-minute cardiac arrest was obtained in 71.4% (5 out of 7 dogs) at the cases with a cold potassium cardioplegic solution (K:23 mEq/L, Na: 25.2 mEq/L) with nicardipine hydrochloride (0.25 mg/L), nicardipine group. At the cases with a cold potassium cardioplegic solution without the nicardipine, control group, however, 100% (7 out of 7 dogs) needed the countershock to get the spontaneous cardiac beat. The nicardipine group showed significantly better recovery results of LVSP, positive dp/dt and negative dp/dt as compared to the control group. The left ventricular distensibility and LVEDP were well-maintained in the nicardipine group. The control group demonstrated a significant increase of myocardial water content after 60-minute reperfusion. The electron microscopic findings revealed that the myocardial ultrastructure in the nicardipine group were less injured as compared to that of the control group. It was concluded that the cold potassium cardioplegic solution with the nicardipine hydrochloride offers superior myocardial protection as compared to that without the nicardipine and is useful in clinical trial. PMID- 2329302 TI - [A study of lung cancer with presence of pleural effusion at the time of thoracotomy--cytologic evaluation of a relatively small amount of pleural effusion and prognosis after removal]. AB - The cytologic evaluation of a relatively small amount of pleural effusion in lung cancer at the time of thoracotomy has not been previously considered, and prognosis after removal has not been clarified. In order to clarify these points, 99 cases of removed lung cancer with presence of pleural effusion at the time of thoracotomy were examined following cytology. Our study was conducted with regard to the amount and nature of pleural effusion, pleural effusion cytology, tumor development and its relation to prognosis. On the basis of this study a formula was developed relating the occurrence rate of cytologically positive pleural effusion with the development of tumor employing multivariate analysis, specifically the multiple regression analysis. 21% of these cases showed cytologically positive pleural effusion, indicating an absence of its correlation to the amount of pleural effusion; the conducting of cytology regardless of the amount of pleural effusion was found to be significant in determining the precise stage. The occurrence rate of cytologically positive squamous cell carcinoma was significantly few compared with those in other cell types. Regarding the pleural effusion of a relatively small amount, the prognosis after removal showed a relatively high three-year survival rate of 32% for those cases with negative pleural metastasis despite the positive showing of pleural effusion cytology, indicating the viability of surgery. From the occurrence rate of cytologically positive pleural effusion (Y) and the degree of pleural metastasis (X1)/the degree of pleural invasion (X2)/the degree of lymph nodes metastasis (X3), the following formula was obtained employing multiple regression analysis: Y = 0.344X1 + 0.050X2 + 0.034X3 + 0.075 (proportion 0.840).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329303 TI - [Surgical management of aneurysm of the ascending aorta with aortic insufficiency]. AB - Twelve patients had elective surgical treatment for the aneurysm of the ascending aorta with aortic insufficiency at the Kanazawa University School of Medicine between 1976 and 1987. There were 9 men and 3 women aged from 26 to 39 years (mean, 33.0 years). Seven patients had a Marfan's syndrome and 6 of these patients also had aortic dissection. Three patients had aortic valve replacement plus supracoronary tube graft (Wheat's operation) and the other 9 patients underwent composite tube graft, with Bentall's operation in 3, Cabrol's operation in 2, and the modified Bentall's operation in which prosthetic valve was offset inside the tube graft in 4. Early deaths accounted for an operative mortality of 16.7%. The mean aortic cross-clamp time and the amount of bleeding were less with the modified Bentall's operation than with the other composite tube graft procedures. This modification seems to decrease the morbidity and to simplify the procedure in treatment of aneurysm of the ascending aorta with aortic insufficiency. There were 2 late deaths of patients with Marfan's syndrome associated with type I aortic dissection. Regular periodic examinations of the patients is needed, especially when Marfan's syndrome is present, in order to detect and surgically correct residual lesions. PMID- 2329304 TI - [An experimental study of reconstruction--differences of the healing process by materials]. AB - The healing processes of carinal reconstruction by suture materials; absorbable suture (Vicryl) and nonabsorbable suture (Prolene) were compared. 67 adult mongrel dogs underwent resection of two rings of the trachea and bilateral main bronchi. This was followed by end-to-end anastomosis of the reconstructed carina and the remaining trachea. 3-0 Vicryl or 3-0 Prolene were used respectively. At some intervals, each anastomosis was removed and was analyzed by bronchoscopy, microangiography, scanning electron microscopy (SEM) and light microscopy. Suture insufficiency occurred in two of 32 anastomosis sutured by Vicryl and four of 35 anastomosis sutured by Prolene sutures. Stenosis developed in one of the Vicryl group and two of the Prolene group. Vicryl showed more inflammation than Prolene for 3 weeks after surgery. In four weeks, the inflammation subsided. Anastomoses were of the same degree in both groups. In microangiography, vascular regeneration was abundant by 3 weeks, which normalized in 4 weeks showing a normal network in both groups. Normalization of the vascular network appeared the earliest at the membranous portion. Scanning electron microscopy showed no difference in the reconstruction of the cilia over the anastomosis area in the both groups. This term was 2 months. The order of reconstruction revealed by SEM was the same as observed by microangiography. But in the Prolene group, it took more than 3 months for the suture material to be completely covered with the epithelium. In light microscopy, inflammation was stronger in the group than by in the Prolene groups, and it continued for 4 weeks suture material could not be found in the anastomosis area with bronchoscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329305 TI - [Surgical therapy of congenital aortic valvular stenosis in neonates and infants]. AB - The preoperative evaluation, surgical course, and early follow-up results of 5 infants less than 4 months of age who underwent aortic valvotomy for severe valvular stenosis between 1983 and 1985 were reviewed to determine the early prognosis of these neonates. Two of the 5 patients had been used respiratory support due to severe congestive heart failure and dyspnea. Emergency aortic valvotomy was performed in all during cardio-pulmonary bypass which achieve maximal relief of the stenosis without significant causing aortic insufficiency. There was a single operative death and there was one late death at 2 months after surgery who was regarded to have a extensive endocardial fibroelastosis. The other three patients have had a favorable early prognosis during mean follow-up period of 1.78 (0.4-3.8) years. They had been followed by means of two dimensional and doppler echocardiography, which inferred that the aortic pressure gradient had been kept under 41 mmHg and which indicated that there were no LV enlargement to prove significant aortic valve insufficiency. These results indicate that early infants with severe valvular stenosis can undergo sufficient valvotomy safely and have a favorable early prognosis. PMID- 2329306 TI - [Gore-Tex grafts for replacement of the superior vena cava in 10 patients with intrathoracic malignant tumors]. AB - Ten patients with lung cancer and mediastinal tumor invading the mediastinal structures underwent replacement of superior vena cava (SVC) with ringed Gore-Tex to resect malignant tumors. In patients with lung cancer sleeve pneumonectomy (3 patients), sleeve lobectomy (1 patients) and tracheal resection (one patient) were performed simultaneously. By resection of the VCS system, invasive thymomas were able to be resected completely in 2 of 3 patients. In 2 patients with mediastinal tumors, one with metastatic testicular chorio carcinoma and one with malignant lymphoma of non-Hodgkin type, aggressive chemotherapy was followed by resection of the residual tumors including VCS. Except for one patient, there was no sign showing disturbance of the venous return in the VCS system in the 5 to 43 months' postoperative follow up period. We conclude that ringed Gore-Tex graft permits the extended operation for intrathoracic malignancies invading the mediastinal structures. PMID- 2329307 TI - [Completion pneumonectomy--a review of 29 cases]. AB - From 1962 through 1988, a total of 29 consecutive patients had completion pneumonectomy (CP). Indications for initial pulmonary resection were primary lung cancer in 27 patients, metastatic lung tumor in 1, and mediastinal tumor with pulmonary invasion in 1. Indications for CP were lung cancer (including local recurrence, pulmonary metastasis from the first lung cancer, and second primary lung cancer) in 21 patients, complications after initial operations in 7, and pulmonary arterial injury during second operation in 1. Severe adhesion of the residual lung and the hilar structures made operative procedures extremely difficult. Injury of pulmonary arteries occurred in 6 patients. Especially, in cases the left upper lobe had been resected previously, deviation of the lower lobe and hilar adhesion lead to operative difficulty. Post-CP bronchial fistula occurred more frequently in what the bronchi had been dissected at more peripheral level than main bronchus, because of some severe hilar adhesions. Operative mortality was 13.8% (9.5% for second lung cancer, 28.5% for post operative complication). Five-year survival for patients with lung cancer was 32.9% according to the Kaplan-Meier method. We conclude that the indications for CP are clinically resectable lung cancer and bronchial stenosis with residual pulmonary organic changes following bronhoplastic procedure. Postoperative bronchofistulae should be managed by other operative procedure. PMID- 2329308 TI - [Retrograde continuous cold blood cardioplegia for aortic valve surgery]. AB - From September 1983 to February 1987, 45 consecutive aortic valve operations were performed using the retrograde continuous cold blood cardioplegia (RCCBC) via the coronary sinus. Except one patient died of stuck valve after aortic and mitral valve replacements, 44 patients were subjected for this study and all survived patients were symptomatically improved. They were divided into two groups according to the aortic cross clamps time (ACCT). Group 1; 23 patients, ACCT within 120 minutes, and Group 2; 21 patients, ACCT exceeding 120 minutes. After the operation blood was taken periodically to check creatine phosphokinase (CPK) and its iso-enzyme creatine-kinase (CK-MB) and GOT etc. Then their levels were compared between the two groups. Although there seemed to be a tendency that the highest levels of these enzymes increase according to the ACCT, there was no significant difference in CK-MB level between the two groups. Judging from the operative results and the postoperative study of enzymatic level, RCCBC is safe and useful for aortic valve surgery, especially when long ACCT is necessary for correcting complicated lesions or when the coronary orifice is not suitable for coronary perfusion in aortic dissection. PMID- 2329309 TI - [Effects of cardioplegic solution and calcium entry blockers on coronary artery contraction]. AB - We studied the effects of the electrolyte composition (K, Ca, Na) and calcium entry blockers of the extracellular fluid on the tension development of isolated canine coronary arterial strips. In 20 mEq/l K solution, 4.7 mEq/l calcium produced coronary artery contraction. This Ca-induced contraction was inhibited dose-dependently by calcium entry blockers-nifedipine, nicardipine, diltiazem and verapamil. In the presence of 20 mEq/l K, the reduction of sodium concentration to 12 mEq/l increased the tension of coronary artery. Calcium entry blockers did not affect this tension development. After 5 or 30 min perfusion of calcium entry blockers, Ca-induced contraction was inhibited. It is concluded that low calcium, high sodium cardioplegic solution or addition of calcium entry blockers may relax the canine coronary artery. PMID- 2329310 TI - [Roles of phospholipids in protein translocation across membranes]. PMID- 2329311 TI - [Kinetic pathway of globular-protein folding]. PMID- 2329312 TI - [Fibrinogen-fibrin conversion]. PMID- 2329313 TI - [Priming mechanisms of the de novo glycogen biosynthesis]. PMID- 2329314 TI - Investigations on red cell size distribution histograms in subjects treated by maintenance haemodialysis. AB - In forty-nine subjects on maintenance haemodialysis quantitative information with respect to changes in the erythron was derived from the red blood cell size distribution histogram. Increased values for the fraction of microcytes were observed in seventeen subjects, whereas in three subjects increased fractions of macrocytes were established. Both fractions were found to be increased simultaneously in only one subject. In the case of normal mean corpuscular volume (MCV) values, the fractions of microcytes were shown to be increased in four male and three female subjects. In contrast, MCV values were increased in four male subjects while the fractions of macrocytes did not exceed the reference range. Several causes which may give rise to abnormalities in red blood cell size distribution histograms in subjects treated by haemodialysis are discussed. From the interpretation of results for serum ferritin concentration, serum iron concentration, total iron binding capacity, and iron saturation percentage it is difficult to establish unequivocally whether the iron supply to the patient is appropriate. PMID- 2329315 TI - Sex dependence of naphthyl butyrate esterase activity in rat serum. AB - The effect of gonadectomy and sex hormone substitution on the activity of naphthyl butyrate esterase in rat serum was investigated. This enzyme was found to be strongly oestrogen-dependent. PMID- 2329316 TI - Spectrophotometric determination of neonatal bilirubin. PMID- 2329317 TI - Calibration of direct reading photometers for the determination of neonatal bilirubin. AB - Blijenberg et al. (J. Clin. Chem. Clin. Biochem. 25, 737-741 (1987) (1)) proposed that the assigned values of calibrators for the determination of bilirubin with simple direct reading photometers (bilirubinometers or "bilimeters") should be determined on the same type of instrument. For this purpose, the instrument is calibrated with neonatal serum, whose bilirubin concentration is determined with a reference method unbiased by matrix effects. In the present study, this procedure was developed and tested. Bilirubin was determined in capillary plasma (n = 30) and venous serum (n = 31) of newborns. Measurements were made by direct spectrophotometry in 4 bilimeters, and by a micromodification of Vink's spectrophotometric method after dilution with caffeine reagent (Vink et al. Clin. Chem. 34, 67-70 (1988) (2)). When the bilimeters were calibrated with a commercial control serum, using the concentrations quoted by the manufacturer, the results were higher by 13% (plasma) and 19% (serum) than those obtained by Vink's method. These discrepancies practically disappeared when the bilimeter results were recalculated using a calibrator concentration determined according to Blijenberg. Application of the proposed method to other control sera gave assigned values up to 23% lower than those stated by the manufacturers. After calibration of the bilimeters with various neonatal sera (specimens drawn for therapeutic purposes and residues, obtained from the clinical laboratory), differences of about 10% were observed between the assigned values. It is therefore essential to use several sera. Minor differences were found between bilimeters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329318 TI - Simultaneous determination of urinary phosphate and sulphate by ion chromatography. AB - An ion-chromatographic system was used for the simultaneous determination of urinary phosphate and sulphate. This method was compared with conventional methods (colorimetric, turbidimetric) with regard to practicability and reliability. All methods showed good precision and accuracy. The comparative analysis of phosphate in 80 samples revealed that both methods lead to identical results. However, in case of sulphate a significant difference of about 8% was found between the two methods. Overestimation of the analyte concentration by the turbidimetric method might be responsible for this difference. From the point of view of economy, routine analysis of urinary phosphate and sulphate by ion chromatography is acceptable only if automated systems are used. PMID- 2329319 TI - Effect of glucose upon alkaline picrate: a Jaffe interference. AB - The reactivity of glucose in aqueous alkaline picrate was investigated by spectrophotometry and polarography at 25 degrees C in 0.51 mol/l sodium hydroxide. Thin-layer chromatography and infrared spectroscopy studies have conclusively identified the presence of picramic acid in 5:1 and 10:1 glucose picrate test solutions incubated at 25 degrees C. The polarographic data of an alkaline picrate blank with a concentration of 0.284 mmol/l, show three well defined nitro group reduction waves with approximate half-wave potentials of 0.62 V, -0.78 V, and -0.93 V and a fourth broad wave appearing near -1.31 V versus a saturated calomel electrode. The addition of glucose to alkaline picrate resulted in a decreased diffusion current for reduction waves 1-3, with little change in reduction wave 4. The reactivity of test solutions containing glucose:picrate in 1:1, 2:1, 5:1 and 10:1 molar ratios was investigated at varied time intervals between 10 and 180 minutes. The absorption spectra of a 10:1 glucose:picrate solution shifted from 356 nm to 375 nm and a broad tailing shoulder absorbance formed in the 450-600 nm region. An orange coloured minor product, separated by thin-layer chromatography, was observed to fluoresce. The maximum excitation and emission wavelengths were 318 nm and 545 nm, respectively. A major, red-coloured product was isolated and identified as picramic acid by infrared spectroscopy. For 10:1 glucose:picrate test solutions incubated at 25 degrees C, picramic acid formed within 10 minutes. Within the first minute, the colour was observed to change from yellow to orange and then to red. PMID- 2329320 TI - Who defines the medical requirements of analytical tests? PMID- 2329321 TI - Myocardial cell damage and breakdown of cation homeostasis during conditions of ischaemia and reperfusion, the oxygen paradox, and reduced extracellular calcium. AB - Enzyme release from perfused rat heart was determined under various conditions of injury. In analogous experiments, intracellular cation concentrations were measured using ion-selective microelectrodes. Under appropriate conditions, the inhibition of mitochondrial and/or glycolytic ATP production led to a decrease in the release of enzymes. During ischaemia or the oxygen paradox, the sarcosolic Ca2+ concentration was highly elevated; reperfusion or reoxygenation was followed by a drastic enzyme release. This was also found to be true under the conditions of an increased permeability brought about by a reduced extracellular Ca2+ concentration of 0.1 mmol/l. The intracellular pH under all conditions of injury was only moderately decreased. The sarcosolic Na+ concentration was markedly increased whereas the K+ concentration was decreased. The critical Ca2+ concentration of the sarcosol beyond which cell damage and enzyme release are inducible was assumed to be in the range between 10 and 32 mumol/l. The driving force of the Na+/Ca2+ exchange reaction of the sarcolemma is discussed in relation to recovery from hypoxic injury and the potential for avoiding cell damage. PMID- 2329322 TI - Determination of cathepsins B and H in sera and synovial fluids of patients with different joint diseases. AB - Synovial fluids and sera of patients with inflammatory and metabolic joint diseases contain different cysteine proteinases. The quantities of cathepsins B and H were determined by newly developed specific enzyme-linked immunoassay tests (ELISA), with detection limits of 0.5 microgram/l for cathepsin B and 3 micrograms/l for cathepsin H. The values of cathepsin B in normal sera ranged from 0.6 microgram/l to 2 micrograms/l, whereas in sera of patients with joint diseases they ranged from 1.7 micrograms/l to 18 micrograms/l. Cathepsin H was not found in sera (values below 3 micrograms/l), but was measurable in patients' synovial fluids. Patients with rheumatoid arthritis have on average the highest values of cathepsin B in synovial fluids, whereas patients with undifferentiated arthritis have the highest values of cathepsin H. The results show that cathepsins B and H are present in arthritic synovial fluids, where they may be implicated in destructive processes. There is yet no clear correlation between the quantity of each cathepsin released in synovia and the clinical diagnosis or the stage of the disease. PMID- 2329323 TI - Adaptation and evaluation of a chromogenic test procedure for fibrin monomers on a centrifugal analyzer. AB - We evaluated a recently introduced quantitative chromogenic substrate test for the determination of fibrin monomers in plasma (Coa-set FM test). The sample and reagent volume, the reaction time and the composition of the zero standard were modified. In its optimized form the test showed good reproducibility and an acceptable linearity range. Freezing and thawing of the samples does not cause problems. The coefficient of correlation in the comparison of the Coa-set FM test and the Boehringer FM test was r = 0.967, whereas the conformity was poor. The reference ranges for males and females were not significantly different, resulting in a universal reference range of 8.4-13.2 nmol/l. In conclusion, the Coa-set FM test is, in the modified form, a precise, quick and sensitive method, which can become a valuable tool in the early detection of circulating fibrin monomers. PMID- 2329324 TI - Immunoassay by particle counting for coagulation testing: application to the determination of protein C. AB - Latex particles coated with F(ab)'2 fragments of anti-protein C IgG antibodies are agglutinated by protein C, and the quantity of particles agglutinated is proportional to the concentration of protein C. The reaction can be quantitated by optical particle counting. Based on this system, we designed an immunoassay for protein C. Precision measured at low, medium and high levels of protein C varied from 3.3% to 13.7%. Specificity was evaluated by dilution recovery. A correlation coefficient of r = 0.959 was found when the new method was compared with a chromogenic technique on 131 plasmas. PMID- 2329325 TI - Handling of blood specimens for glucose analysis. AB - There is no consensus concentration of sodium fluoride (NaF) required for preserving glucose in blood specimens. We examined the effectiveness of different concentrations of NaF. Glucose concentration in blood samples decreased with time, despite the presence of a high concentration of NaF (12 g/l). The decrease in glucose concentration was less with increasing amounts of NaF but could not be totally abolished. The clinical implications of these pre-analytical errors is discussed. PMID- 2329326 TI - Discussion of "The Shielding Capacity of the Standard Military Flak Jacket Against Ballistic Injury to the Kidney". PMID- 2329327 TI - Discussion of "Validity Testing of Commercial Urine Cocaine Metabolite Assays: Parts I and II". PMID- 2329328 TI - Discussion of "A Case of Panhypogammaglobulinemia Masquerading as Child Abuse" with regard to the involution of the thymus. PMID- 2329329 TI - The forensic science implications of site and temporal influences on postmortem blood-drug concentrations. AB - The dependence of postmortem blood-drug concentrations on the collection site and on the postmortem interval before specimen collection has been studied. These studies consisted of both sequential sampling from the same collection site at defined time intervals and a comparison of the drug concentrations of postmortem blood simultaneously collected from various sites. A site and time dependence was observed for postmortem blood-drug concentrations. The heart blood-drug concentrations were, in general, significantly higher than those of peripheral specimens. As a result of this phenomenon, the analysis of peripheral blood specimens and solid tissues is often necessary before a definitive interpretation of postmortem toxicological analyses is possible. PMID- 2329330 TI - The cocaine body-packer syndrome: evaluation of a method of contrast study of the bowel. AB - The questionable reliability of the conventional procedures for detection of ingested drug packages triggered us to evaluate the accuracy of a method of contrast study of the bowel in 23 nonsurgically managed cocaine body-packers. A single dose (60 mL) of a water-soluble contrast compound (amidotrizoate + meglumine) was given orally after initial clinical examination and drug detection in urine. Thereafter, roentgenograms were performed daily after spontaneous passage until obtaining two packet-free stools and negative views. Roentgenograms showed packages when performed at least 3 h after the ingestion of the contrast compound. Sensitivity and specificity of the method with respect to the detection of residual packets in the body, assessed by subsequent examination of stools, was good and did not diminish as the number of packages decreased during the time spent in ward. No side-effects were observed. We conclude that oral administration of a water-soluble contrast compound is an easily performed, efficient, and safe method for the nonsurgical management of cocaine body packers. PMID- 2329331 TI - Death as a result of asthma in Wayne County Medical Examiner cases, 1975-1987. AB - All deaths ascribed to asthma in the 5-to-40-year age group at the Wayne County Medical Examiners' Office were reviewed from 1975 to 1987 inclusive. Fifty-eight deaths were attributed solely to asthma, and the annual number increased fivefold in the 1980s to a rate of approximately 0.5 per 100,000 per year when extrapolated to the Wayne County population. Blacks were overrepresented to double their proportion in the general population. Almost all cases were known asthmatics, and many had received previous emergency care. Most fatalities occurred at night and did not demonstrate any seasonal variation. The onset of the fatal attack was apparently very rapid in most cases, with many engaged in routine activities and few surviving any length of time in hospital or having sought treatment earlier. Our data reveal a significant increase in sudden death in previously well asthmatics in Wayne County in the 1980s. Similar increases in deaths as a result of asthma have been noted previously in other countries for reasons that remain unclear. PMID- 2329332 TI - The significance of postmortem radiographs in infants. AB - The radiographs of 108 infants were analyzed prospectively before autopsy to correlate radiographic findings with those found at the postmortem examination. There was poor correlation between radiographs and autopsy findings when pulmonary pathology was present, and there was no gut pathology when radiographs revealed portal venous air. The radiographs were most helpful when either bony abnormalities (that is, fractures or congenital abnormalities) or free air were found before autopsy. PMID- 2329333 TI - Sleep violence--forensic science implications: polygraphic and video documentation. AB - During the past century, infrequent, anecdotal reports of sleep-related violence with forensic science implications have appeared. Recent rapid developments in the field of sleep-disorders medicine have resulted in greater understanding of a variety of sleep-related behaviors, and formal sleep-behavior monitoring techniques have permitted their documentation and classification. Sleep-related violence can be associated with a number of diagnosable and treatable sleep disorders, including (1) night terrors/sleepwalking, (2) nocturnal seizures, (3) rapid eye movement (REM) sleep-behavior disorder, (4) sleep drunkenness, and (5) psychogenic dissociative states occurring during the sleep period. Potentially violent automatized behavior, without consciousness, can and does occur during sleep. The violence resulting from these disorders may be misinterpreted as purposeful suicide, assault, or even homicide. Sleep-related violence must be added to the list of automatisms. A classification system of both waking and sleep-related automatic behavior is proposed, with recommendations for assessment of such behavior. PMID- 2329334 TI - Prison mental health services: results of a national survey of standards, resources, administrative structure, and litigation. AB - The formation of adequate mental health systems within prisons has accelerated as a result of successful class action lawsuits. Our recent national survey questioned all state correctional departments about the existence of standards in each system, compliance with such standards, prevalence of class action lawsuits involving the issue of providing adequate mental health services for inmates, issues related to consent decrees, available mental health resources within the correctional system, and the administrative structure of the mental health system. Our purpose was to identify those factors correlated with certified class action lawsuits involving issues related to mental health services. Twenty-one states were involved in such litigation. Only the presence of psychiatric hospitals operated by the department of corrections correlated with the presence of certified class action lawsuits involving mental health services. Prison systems larger than 15,000 inmates were at higher risk for such litigation. Smaller systems having psychiatric hospitals run by the state mental health agency appeared to be at less risk for such litigation. PMID- 2329335 TI - A modification of the microplate method for reverse ABO typing of bloodstains and additional validation studies. AB - The results of additional validation studies of a sensitive microplate hemagglutination assay for ABO reverse grouping of bloodstains are presented. The results of the validation study demonstrate the reliability of the microplate assay for use in routine serological casework. Based on these studies, the microplate assay has now replaced the Lattes crust test for ABO reverse grouping of bloodstains in the FBI Laboratory. PMID- 2329336 TI - The effects of heat upon the glyoxalase I isoenzyme. AB - It was observed during the course of routine casework that different bloodstains from the same individual could produce anomalies in the glyoxalase I band patterns. Bloodstains were heated at different temperatures for periods of 4 and 6 h and then examined using electrophoretic techniques. It was demonstrated that upon heating, band alterations in the glyoxalase I Type 1 phenotype can occur, causing the analyst to render the results inconclusive. PMID- 2329337 TI - Positive identification of American Indian skeletal remains from radiograph comparison. AB - The case reported here documents how comparative data gleaned from study of museum collections enabled positive identification of an American Indian homicide victim through radiograph comparison. In particular, the shape of the lateral border of the scapula proved to be a unique anatomical feature, appropriate for establishing positive identification. PMID- 2329338 TI - Single wound produced by simultaneous discharge of both shells from a double barrel shotgun. AB - We present the case of a man who was killed by simultaneous discharge of both barrels of a double-barrel shotgun. Externally, there was a single wound simulating a wound made by a discharge of a single barrel. Test-firing of the shotgun against cloth, paper, and naugahyde targets revealed defects similar in shape to the wound in the victim. Simultaneous discharge of both barrels from a double-barrel shotgun may simulate the wound made by discharge of a single barrel. PMID- 2329339 TI - A fatal interaction of methocarbamol and ethanol in an accidental poisoning. AB - A case is presented of a fatal drug interaction caused by ingestion of methocarbamol (Robaxin) and ethanol. Methocarbamol is a carbamate derivative used as a muscle relaxant with sedative effects. Therapeutic concentrations of methocarbamol are reported to be 24 to 41 micrograms/mL. Biological fluids were screened for ethanol using the Abbott TDx system and quantitated by gas-liquid chromatography (GLC). Determination of methocarbamol concentrations in biological tissue homogenates and fluids were obtained by colorimetric analysis of diazotized methocarbamol. Blood ethanol concentration was 135 mg/dL (0.135% w/v) and urine ethanol was 249 mg/dL (0.249% w/v). Methocarbamol concentrations were: blood, 257 micrograms/mL; bile, 927 micrograms/L; urine, 255 micrograms/L; gastric, 3.7 g; liver, 459 micrograms/g; and kidney, 83 micrograms/g. The combination of ethanol and carbamates is contraindicated since acute alcohol intoxication combined with carbamate usage can lead to combined central nervous system depression as a result of the interactive sedative-hypnotic properties of the compounds. PMID- 2329340 TI - A dextromoramide-related fatality. AB - A 38-year-old man was found in his car suffering from a heart attack. Serum analysis by capillary gas chromatography and mass spectrometry confirmed the presence of dextromoramide (Palfium), methadone, and lidocaine. The serum concentrations at admission to the hospital were: 1.9 micrograms/mL of dextromoramide, 0.4 micrograms/mL of methadone, and 0.4 micrograms/mL of lidocaine. A serum alcohol analysis performed using headspace gas chromatography was negative. PMID- 2329341 TI - Killer pop machines. AB - Abuse and misuse of soda vending machines has resulted in a considerable number of injuries and deaths. The machines fall forward when rocked or tilted and crush those in front. These accidents are all preventable by a simple and cheap device. There should be a law compelling safety requirements for these machines. This is a report of a recent case in which a young man was crushed to death. PMID- 2329342 TI - Nonfracture-associated fatal fat embolism in a case of child abuse. AB - Fatal fat embolism is usually thought of as a sequel to long-bone fracture, although cases secondary to soft tissue injury and atraumatic conditions have been infrequently reported. In this case of a two-year-old child-abuse victim who sustained multiple blunt traumatic injuries without skeletal fractures, pulmonary and systemic (brain and kidney) fat emboli were identified. At autopsy, all thoracic and abdominal viscera were intact; cranial contents exhibited only diffuse symmetrical petechial hemorrhages of the white matter. Because of the severe and widespread nature of soft tissue hemorrhage, and the absence of a grossly discernible cause of death, fat embolism was suspected. Using a combination of frozen section with oil red O staining and formalin-fixed osmium stained tissues, the immediate cause of death was determined to be diffuse fat embolism. Review of the literature reveals a pathophysiologic basis for fat embolism in the absence of fracture, both as a consequence of an acute increase in local pressure at the site of trauma and an alteration of the emulsification of blood lipids during shock. In light of these findings, we present this case to remind the forensic science community to consider fat embolism as the cause of death in cases of blunt-force injury without fracture. PMID- 2329343 TI - Bioaccumulation of nickel and vanadium in tissues of the catfish Clarias batrachus. AB - Bioaccumulation of nickel and vanadium in the tissues of the liver, kidney, gill, and intestine has been studied following 4 days and 30 days of exposure at sublethal concentrations of nickel and vanadium compounds in the catfish Clarias batrachus. Nickel and vanadium have been found to accumulate in all four tissues observed. High concentrations of nickel and vanadium have been found in the order kidney greater than gill greater than liver greater than intestine during the 4 days and 30 days treatment. A dose-response effect was seen, as the concentration of metals in the tissues increased with concentration and exposure time. The effect on bioaccumulation in the specific tissue provides a better basis for monitoring exposures than whole-body analysis. PMID- 2329344 TI - Site selectivity in the binding of inorganic anions to serum transferrin. AB - Equilibrium constants for the sequential binding of two anions at the specific metal-binding sites of apotransferrin have been measured by difference ultraviolet spectroscopy in 0.1 M N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes) at pH 7.4 and 25 degrees C. Log K1 values for phosphate, phosphite, sulfate, and arsenate fall in the narrow range of 3.5-4.0, while the log K1 for bicarbonate is 2.73. No binding is observed for nitrate, perchlorate, or borate. A dinegative charge appears to be the most important criterion for anion binding. Equilibrium constants have also been measured for binding of anions to both forms of mono(ferric)transferrin. There appears to be a very small site selectivity (0.2 to 0.4 log units) for phosphate, arsenate, and phosphite that favors binding to the N-terminal site, but there is no detectable selectivity for binding of sulfate or bicarbonate. Comparison of the binding affinities and anion selectivity with literature data on anion-binding to protonated macrocyles and cryptates strongly supports the existence of specific anion-binding sites on the protein. Binding constants were also measured in 0.01 M Hepes. The anionic sulfonate group of the buffer appears to have a small effect on anion binding. PMID- 2329345 TI - Platinum and palladium complexes of 3-methyl orotic acid: a route toward palladium complexes with good antitumor activity. AB - In order to design and develop potential anticancer drugs involving the same structural pattern as platinum(II) antitumor complexes, complexes of palladium and platinum with 3-methyl-orotic acid as the leaving ligand have been synthesized. The study of the anticancer activity of these compounds toward L1210 leukemia and sarcoma 180 in mice is presented and discussed in terms of the nature of the ligand and the metal involved. The (3-methylorotato)(1,2-diamino cyclohexane) palladium(II) has an activity (sarcoma 180) similar to that for cis DDP itself. The crystal structure of (3-methylorotato)(dl-trans-1,2 diaminocyclohexane) platinum(II) is described. PMID- 2329346 TI - Aluminum speciation studies in biological fluids. Part 3. Quantitative investigation of aluminum-phosphate complexes and assessment of their potential significance in vivo. AB - Following the discovery that specific health disorders affecting patients with renal disease were due to their excessive body accumulation of aluminum, it was established that aluminum toxicity was mainly due to the ingestion of aluminum containing phosphate binders. Suspicion of toxicity was thus cast on aluminum containing antacids, and subsequent tests held on healthy subjects did reveal that aluminum hydroxide gels were also potential oral sources of aluminum, especially in the presence of citric acid. Nevertheless, authors of these tests concluded that there was only marginal absorption of aluminum phosphate. In contrast with these clinical conclusions, it has recently been contended on theoretical grounds that aluminum phosphate represents a serious health hazard. To help elucidate this issue, this paper first deals with a quantitative investigation of aluminum-phosphate equilibria under physiological conditions. Then appropriate computer simulations based on corresponding results are used to assess the actual extent to which phosphate can influence aluminum bioavailability. These simulations confirm that aluminum phosphate is not expected to induce absorption of high amounts of aluminum when administered by itself. Nevertheless, this result may no longer apply in the presence of food, whose various acidic components are likely to modify the involved chemical equilibria. Moreover, it is shown that rising blood plasma phosphate levels should tend to increase aluminum tissue penetration and hence favor its potential toxicity. PMID- 2329347 TI - Congestive heart failure. PMID- 2329348 TI - Outcome standards for the client with chronic congestive heart failure. AB - This article discusses the outcome standards for the client with chronic congestive heart failure. The pathophysiology of chronic congestive heart failure is explained and used as a basis for the outcome standards nurses need to strive for in this patient population. This article outlines the basic outcome standards for this patient population and aspires to open the doorway for further research into the needs of the client with chronic congestive heart failure. PMID- 2329349 TI - Critical dimensions of chronic care. Nursing grand rounds. AB - Due to the increasing level of acuity in today's long-term population, interventions previously found only in acute care are now becoming commonplace in the chronic care setting. These changes result from health care and reimbursement legislation, advances in medical technology and the overall increased life expectancy of the population at large. To meet these challenges, nursing leaders are making efforts to identify and anticipate patient care needs, and to implement educational programs for staff to meet those needs. One of those interventions, inotropic therapy, is being seen more frequently in the long-term care setting. This article describes how one facility managed the administration of inotropic agents to a patient with end stage cardiac disease, and some of the issues surrounding initiation of the drug. PMID- 2329350 TI - Recurrent inhibition to and from motoneurons innervating the flexor digitorum and flexor hallucis longus muscles of the cat. AB - 1. Recurrent inhibitory postsynaptic potentials (IPSPs) to and from motoneurons innervating the flexor digitorum longus (FDL) and flexor hallucis longus (FHL) muscles of the cat were investigated to determine whether recurrent inhibitory projections involving these motoneurons are similar--as would be consistent with the Ia and anatomic synergism of FDL and FHL--or are dissimilar, as are the activities of these muscles during locomotion (O'Donovan et al. 1982). 2. Composite recurrent IPSPs were recorded in several species of motoneurons innervating hindlimb muscles in response to stimulation of a number of muscle nerves in cats allowed to become unanesthetized after ischemic decapitation. 3. No recurrent IPSPs from stimulation of the FDL nerve were observed in motoneurons innervating FDL, FHL, lateral gastrocnemius-soleus (LG-S), medial gastrocnemius (MG), plantaris (Pl), tibialis anterior (TA), or extensor digitorum longus (EDL). 4. The recurrent IPSPs produced by stimulation of FHL were larger and found more frequently in LG-S than in FDL motoneurons. Recurrent inhibition from FHL was also greater in Pl than in FDL motoneurons. 5. The recurrent IPSPs produced by stimulation of LG-S, PL, and MG were larger in FHL than in FDL motoneurons, and those from LG-S and MG were found more frequently in FHL than in FDL motoneurons. 6. Stimulation of the TA nerve produces recurrent IPSPs in FDL but not in FHL motoneurons. A few FDL and FHL cells (6 of 23 and 9 of 34, respectively) received small (less than 0.5 mV) recurrent IPSPs from stimulation of the EDL nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329351 TI - Modulation by a moving texture of cat area 18 neuron responses to moving bars. AB - 1. The influence of a moving texture on neuronal responses to a moving bar was tested in 103 area 18 neurons of anesthetized and paralyzed cats. The texture was a two-dimensional noise pattern, the bar moved at optimal speed, and its contrast was adjusted to yield 50% of the maximum response. 2. The moving texture exerted two different but related effects: it suppressed the response of area 18 neurons to the moving bar, and it modulated the direction selectivity of parastriate neurons. These effects were strongest when the texture moved at the same speed or faster than the bar. 3. Genuine suppressive effects of the moving texture were distinguished from lack of summation between bar and texture responses. Suppressive effects of either type were observed in 75% of the area 18 cells and occurred more frequently among C family cells, velocity tuned cells, and in layer 5 than in other groups of cells. 4. The modulation of direction selectivity was distinguished from pseudomodulation because of lack of summation of bar and texture responses. The direction selectivity of 35% of the area 18 cells was modulated by the moving texture. Six different relative direction selectivity (RDS) types were observed in area 18. 5. The neurons of which direction selectivity was modulated by the moving texture occurred predominantly in layers 2-3 and 6, suggesting that they represent a further stage of processing within area 18. 6. Many (75%) area 18 cells responded to the texture moving on its own. Most of these cells respond to isolated features ("grains") in the patterns rather than to the movement of the whole pattern. Cells responding to the movement of the whole pattern were generally C family cells, and their direction selectivity was not modulated by the moving texture. 7. These results are compared with those obtained under identical experimental conditions in area 17. Although suppressive effects are similar in both areas, RDS types are differently distributed in the two areas. 8. The possible origins of the interactions and their functional significance are discussed. PMID- 2329352 TI - Ascending pathways in the spinal cord involved in the activation of subnucleus reticularis dorsalis neurons in the medulla of the rat. AB - 1. Recordings were made from neurons in the left medullary subnucleus reticularis dorsalis (SRD) of anesthetized rats. Two populations of neurons were recorded: neurons with total nociceptive convergence (TNC), which gave responses to A delta and C-fiber activation from the entire body after percutaneous electrical stimulation, and neurons with partial nociceptive convergence (PNC), which responded to identical stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-fiber peak of activation from some, mainly contralateral, parts of the body. 2. The effects of various, acute, transverse sections of the cervical (C4-C5) spinal cord on the A delta- and C-fiber-evoked responses were investigated by building poststimulus histograms (PSHs) after 50 trials of supramaximal percutaneous electrical stimulation of the extremity of either hindpaw (2-ms duration; 3 times threshold for C-fiber responses), before and 30-40 min after making the spinal lesion. 3. In the case of TNC neurons, hemisections of the left cervical cord blocked the responses elicited from the right hindpaw and slightly, but not significantly, diminished those evoked from the left hindpaw. Conversely, hemisections of the right cervical cord abolished TNC responses elicited from the left hindpaw without significantly affecting the responses elicited from the right hindpaw. 4. Lesioning the dorsal columns or the left dorsolateral funiculus was found not to affect the TNC neuronal responses elicited from either hindpaw. By contrast, lesioning the left lateral funiculus or the most lateral part of the ventrolateral funiculus, respectively, reduced and blocked the responses elicited from the right hindpaw without affecting those evoked from the left hindpaw. 5. After lesions that included the most lateral parts of the left ventral funiculus, PNC neuronal responses elicited from the right hindpaw were also abolished, whereas those elicited from the left hindpaw remained unchanged. 6. We conclude that the signals responsible for the activation of SRD neurons travel principally in the lateral parts of the ventrolateral quadrant, a region that classically has been implicated in the transmission of noxious information. Both a crossed and a double-crossed pathway are involved in this process. The postsynaptic fibers of the dorsal columns and the spinocervical and spinomesencephalic tracts do not appear to convey signals that activate SRD neurons. 7. The findings also suggest that lamina I nociceptive specific neurons, the axons of which travel within the dorsolateral funiculus, do not contribute very much to the activation of SRD neurons. PMID- 2329353 TI - Triggering of preprogrammed movements as reactions to masked stimuli. AB - 1. Visual stimuli were presented to normal human subjects to test simple and more complex voluntary motor responses. Large and small visual stimuli were presented. In some trials, the small stimulus was followed 50 ms later by the large stimulus, so that the small stimulus was not perceived; this is the phenomenon of "backward masking." 2. Although subjects were not able to detect the masked, visual stimulus on forced-choice testing, they performed motor, reaction-time (RT) tasks in response to it. The RTs for responses to the masked stimulus were the same as those for responses to the easily perceived, nonmasked stimulus. 3. This result confirms and extends the findings of Fehrer and Biederman and was demonstrated with both simple and more complex motor responses. 4. Discussion of the findings focuses on their implications for motor control, particularly with respect to the preprogramming of voluntary movement. PMID- 2329354 TI - Response similarity to odors in olfactory bulb output cells presumed to be connected to the same glomerulus: electrophysiological study using simultaneous single-unit recordings. AB - 1. The glomeruli of the olfactory bulb are discrete anatomic structures in which the terminals of receptor cell axons make extensive contacts with the primary dendrites of the mitral and tufted output cells. In mammals, each mitral and deep tufted (M/T) cell possesses a single primary dendrite and sends it toward the glomerulus situated just in front of its somata. 2. We tested the hypothesis that the glomeruli, which appear to form anatomic units, could act to some extent as functional units. A unitary functioning implies that the M/T cells connected to the same glomerulus will more often display similar responses to odorants than cells having no common glomerular relationships, including cells related to adjacent glomeruli. 3. In anesthetized adult rats, we recorded the extracellular single-unit responses of pairs of M/T cells to a series of five odorants. Recordings were performed with the use of twin microelectrodes whose tips were separated either by less than 40 or by 150-200 microns. Because of the olfactory bulb organization, we assumed that the close cells, recorded at a distance less than 40 microns, were more often connected to the same glomerulus, whereas the distant cells, recorded at a distance of 150-200 microns, were more often connected to adjacent glomeruli. 4. Stimulus-evoked changes in firing rate were classified as either excitatory (+), suppressive (-), or null (0) responses. The collection of response types of a given cell to the 5 odorants composed its response profile. Response profiles were used to compare the responsiveness within close and within distant cell pairs with that observed within control pairs of cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329355 TI - Movement-related phasic muscle activation. I. Relations with temporal profile of movement. AB - 1. The role of phasic muscle activation in determining the temporal properties of human arm movements was studied. The experiments show that subjects can modulate the triphasic electromyographic (EMG) pattern to produce movements of varied temporal structures. 2. Subjects performed horizontal forearm movements in which they varied movement accelerations and decelerations. All movements were of the same amplitude, duration, and peak velocity. A phase-plane (velocity vs. position) template of the desired movement was presented to the subject, who had to reproduce the template by appropriate movement of the forearm. 3. The ratio of the durations of acceleration to deceleration (termed the symmetry ratio, SR) was used as a measure of the temporal structure of the movements. Movements with SRs ranging from 0.4 (short acceleration-long deceleration) to 2.0 (long acceleration short deceleration) were studied. 4. Subjects modulated the components of the triphasic EMG pattern to produce movements with different temporal profiles. As the SR was increased (increasing acceleration duration-decreasing deceleration duration), the following changes occurred: 1) the duration of the initial agonist burst (AG1) increased while its magnitude decreased; 2) the antagonist burst (ANT1) was progressively delayed relative to movement onset. ANT1 magnitude increased while its duration remained constant; and 3) the magnitude of the second agonist burst (AG2) increased and its duration decreased. 5. The triphasic EMG pattern can be modified to produce movements whose velocity profiles are not the same under simple scaling of duration or magnitude. It is concluded that previously described relations between components of the triphasic EMG pattern and movement parameters, such as amplitude, speed, and duration, are secondary to associated changes in their acceleration and deceleration characteristics. PMID- 2329356 TI - Movement-related phasic muscle activation. II. Generation and functional role of the triphasic pattern. AB - 1. Electromyographic (EMG) activity of arm movements made at constant velocity was studied in humans. In these movements, acceleration was temporally separated from deceleration by a period of constant velocity (zero acceleration) lasting up to 600 ms. 2. Agonist (AG1) and antagonist (ANT1) bursts were associated with acceleration. AG1 began before acceleration onset. ANT1 started after the onset of AG1 and was often partially coextensive with AG1. The initial phasic activity was followed by tonic EMG activity during the constant-velocity phase of the movements. Movement deceleration was associated with an antagonist burst (ANT2) and an agonist (AG2) burst. 3. Subjects could alter the magnitudes of the acceleration- and deceleration-related activities independently, with resulting independent changes in the movement acceleration and deceleration. 4. When the duration of the constant-velocity phase was decreased, the agonist/antagonist burst pairs occurred progressively closer in time. When movement duration was decreased to the point at which the velocity profile resembled that of step tracking movements, the four periods of phasic EMG activity formed the classic triphasic pattern. 5. Triphasic EMG patterns were occasionally seen at the beginning or end of long-duration, constant-velocity movements. When they occurred, these triphasic patterns were associated with an acceleration/deceleration pattern similar to that seen in step-tracking movements. 6. The data indicate that paired agonist/antagonist activation is the basic unit of movement control. The AG1/ANT1 burst pair determines the increase and decrease of acceleration, respectively, and the ANT2/AG2 burst pair the increase and decrease of deceleration. These muscle activation pairs can be combined as needed to produce movements having different temporal characteristics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329357 TI - The spino(trigemino)pontoamygdaloid pathway: electrophysiological evidence for an involvement in pain processes. AB - 1. Neurons were recorded in the parabrachial (PB) area, located in the dorsolateral region of the pons (with the use of extracellular micropipette), in the anesthetized rat. Parabrachioamygdaloid (PA) neurons (n = 67) were antidromically identified after stimulation in the centralis nucleus of the amygdala (Ce). The axons of these neurons exhibit a very slow conduction velocity, between 0.26 and 1.1 m/s, i.e., in the unmyelinated range. 2. These PA neurons were located in a restricted region of the PB area: the subnuclei external lateral (PBel) and external medial (PBem). A relative somatotopic organization was found in this region. 3. These units were separated into two groups: 1) a group of nociceptive-specific (NS) neurons (69%), which responded exclusively to noxious stimuli, and 2) a group of nonresponsive (NR) neurons (31%). 4. The NS neurons exhibited low or lacked spontaneous activity. They responded exclusively to mechanical (pinch or squeeze) and/or thermal (waterbath or waterjet greater than 44 degrees C) noxious stimuli with a marked and sustained activation with a rapid onset and generally without afterdischarge. Noxious thermal stimuli generally induced a stronger response than the noxious mechanical stimuli. These neurons exhibited a clear capacity to encode thermal stimuli in the noxious range: 1) the stimulus-response function was always positive and monotonic; 2) the slope of the curve progressively increased up to a maximum where it was very steep, then the steepness of the slope decreased close to the maximum response; and 3) the mean threshold was 44.1 +/- 2 degrees C, and the point of steepest slope of the mean curve was around 47 degrees C. 5. The excitatory receptive fields of the NS neurons were large in the majority (70%) of the cases and included several areas of the body. A more marked activation was often obtained from stimuli applied to one part of the body, denoted as the preferential receptive field (PRF). In the other cases (30%), the excitatory receptive field was relatively small (SRF) and restricted to one part of the body (the tail, a paw, a hemiface, or the tongue). Both the PRF and SRF were more often located on the contralateral side. In addition, noxious stimuli applied outside the excitatory receptive field were found to strongly inhibit the responses of NS neurons. 6. All the NS neurons responded to intense transcutaneous electrical stimulation applied to the PRF or SRF with two peaks of activation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329358 TI - Effect of passive eye position changes on retinogeniculate transmission in the cat. AB - 1. Extracellular recordings were made from single neurons in layer A of the left dorsal lateral geniculate nucleus (LGNd) of anesthetized and paralyzed adult cats. Responses to retinotopically identical visual stimuli (presented through the right eye) were recorded at several positions of the left eye in its orbit. Visual stimuli consisted of drifting sinusoidal gratings of optimal temporal and spatial frequencies at twice threshold contrast. Visual stimulation of the left eye was blocked by a variety of methods, including intravitreal injection of tetrodotoxin (TTX). The change in position of the left eye was achieved by passive movements in a randomized and interleaved fashion. Of 237 neurons studied, responses were obtained from 143 neurons on 20-100 trials of identical visual stimulation at each of six eye positions. Neurons were classified as X- or Y- on the basis of a standard battery of physiological tests (primarily linearity of spatial summation and response latency to electrical stimulation of the optic chiasm). 2. The effect of eye position on the visual response of the 143 neurons was analyzed with respect to the number of action potentials elicited and the peak firing rate. Fifty-seven (40%) neurons had a significant effect [by one factor repeated-measure analysis of variance (ANOVA), P less than 0.05] of eye position on the visual response by either criterion (number of action potentials or peak firing rate). Of these 57 neurons, 47 had a significant effect (P less than 0.05) with respect to the number of action potentials and 23 had a significant effect (P less than 0.05) by both criteria. Thus the permissive measure by either criterion and the conservative measure by both criteria resulted in 40% and 16%, respectively, of all neurons' visual responses being significantly affected by eye position. 3. For the 47 neurons with a significant effect of eye position (number of action potentials criterion), a trend analysis of eye position versus visual response showed a linear trend (P less than 0.05) for 9 neurons, a quadratic trend (P less than 0.05) for 32 neurons, and no significant trend for the 6 remaining neurons. The trends were approximated with linear and nonlinear gain fields (range of eye position change over which the visual response was modulated). The gain fields of individual neurons were compared by measuring the normalized gain (change in neuronal response per degree change of eye position). The mean normalized gain for the 47 neurons was 4.3. 4. The nonlinear gain fields were generally symmetric with respect to nasal versus temporal changes in eye position.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329359 TI - Effect of passive eye movement on retinogeniculate transmission in the cat. AB - 1. The nature and time window of interaction between passive phasic eye movement signals and visual stimuli were studied for dorsal lateral geniculate nucleus (LGNd) neurons in the cat. Extracellular recordings were made from single neurons in layer A of the left LGNd of anesthetized paralyzed cats in response to a normalized visual stimulus presented to the right eye at each of several times of movement of the left eye. The left eye was moved passively at a fixed amplitude and velocity while varying the movement onset time with respect to the visual stimulus onset in a randomized and interleaved fashion. Visual stimuli consisted of square-wave modulated circular spots of appropriate contrast, sign, and size to elicit an optimal excitatory response when placed in the neurons' receptive field (RF) center. 2. Interactions were analyzed for 78 neurons (33 X-neurons, 43 Y-neurons, and 2 physiologically unclassified neurons) on 25-65 trials of identical visual stimuli for each of eight times of eye movement. 3. Sixty percent (47/78) of the neurons tested had a significant eye movement effect (ANOVA, P less than 0.05) on some aspect of their visual response. Of these 47 neurons, 42 (89%) had a significant (P less than 0.05) effect of an appropriately timed eye movement on the number of action potentials, 36 (77%) had a significant effect on the mean peak firing rate, and 31 (66%) were significantly affected as evaluated by both criteria. 4. The eye movement effect on the neurons' visual responses was primarily facilitatory. Facilitation was observed for 37 (79%) of the affected neurons. For 25 of these 37 neurons (68%), the facilitation was significant (P less than 0.05) as evaluated by both criteria (number of action potentials and mean peak firing rate). Ten (21%) of the affected neurons had their visual response significantly inhibited (P less than 0.05). 5. Sixty percent (46/78) of the neurons were tested for the effect of eye movement on both visually elicited activity (visual stimulus contrast = 2 times threshold) and spontaneous activity (contrast = 0). Eye movement significantly affected the visual response of 23 (50%) of these neurons. However, spontaneous activity was significantly affected for only nine (20%) of these neurons. The interaction of the eye movement and visual signals was nonlinear. 6. Nine of 12 neurons (75%) tested had a directionally selective effect of eye movement on the visual response, with most (8/9) preferring the temporal ward direction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329360 TI - Premotor neurons B51 and B52 in the buccal ganglia of Aplysia californica: synaptic connections, effects on ongoing motor rhythms, and peptide modulation. AB - 1. Two buccal ganglia interneurons, labeled here as B51 and B52, have been identified on the basis of morphological and physiological criteria. 2. These neurons have multipolar cell bodies. B51 extends a major neurite, which arborizes in the neuropil ipsilateral to the soma; extends into the buccal commissure, where it branches profusely; and projects an axon out the radular nerve (n1); other processes emanating from the soma arborize in the adjacent cell body layer. B52 arborizes ipsilateral to its cell body and sends a major process out of the ipsilateral hemiganglion into the sheath that attaches the buccal ganglia to the buccal mass proper. Here the B52 axon projects through a previously undescribed structure, which forms an arch over the buccal commissure that we designate the commissural arch. The extraganglionic B52 axon sends several branches into the connective tissue and then returns to the contralateral hemiganglion, where it again branches. 3. Each neuron exhibits a unique set of physiological properties. B51 frequently produces plateau potentials, which persist and are even enhanced in solutions where Ca2+ is replaced with Co2+. On the other hand, B52 shows a powerful posthyperpolarization rebound that contributes to its burst formation during spontaneous and nerve-elicited cyclic motor output. 4. B51 and B52 display distinctive rhythmic bursting on stimulation of the radular nerve or esophageal nerve. Their burst-firing tended to occur at certain phase relationships with respect to firing in other buccal premotor and motor neurons. 5. When firing frequency is measured as a function of intracellularly injected current, B51 shows a steplike increase in firing with increasing current, whereas B52 firing frequency is continuously graded. 6. B51 and B52 were found to make extensive synaptic connections within the buccal ganglia. B51 exhibited primarily excitatory electrical connections with known premotor and motor neurons, including an electrotonic synapse with its contralateral homologue. 7. In contrast, B52 made bilateral inhibitory synapses with nearly all of the premotor and motor neurons of the ventral motor cluster. Most of these connections appeared to be monosynaptic, producing synaptic potentials with short and fixed latencies that persisted when the ganglia were bathed in solutions containing elevated concentrations of Ca2+ and Mg2+. 8. Other synaptic potentials produced by B52 were more variable in size and latency; these included slow inhibition of the B4 and B5 neurons and excitation of an identifiable neuron that projected out the radular nerve.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329361 TI - Responses of nociceptive SI neurons in monkeys and pain sensation in humans elicited by noxious thermal stimulation: effect of interstimulus interval. AB - 1. Twenty-six nociceptive neurons in the primary somatosensory cortex (SI) of anesthetized monkeys were responsive to noxious thermal stimulation applied to the face. Thermode temperature increased from a base line of 38 degrees C to temperatures ranging from 44 to 49 degrees C (T1). After a period of 5 s, the temperature increased an additional 1 degree C (T2). The neuronal responses to noxious thermal stimuli were compared when the interstimulus interval (ISI) was 30 or 180 s. 2. A linear regression analysis was applied to the stimulus-response functions of neuronal responses to T1 stimuli obtained at ISIs of 180 s. Based on the slopes and linear regression coefficients of these stimulus-response functions, two populations of nociceptive neurons were identified. The neuronal responses of one population of nociceptive SI neurons (WDR1) to T1 stimuli were characterized by steep slopes and high regression coefficients, whereas the other population (WDR2) had flatter slopes and lower regression coefficients. WDR1 neurons responded with monotonic increases in neuronal activity as the stimulus intensity increased. However, the peak frequency of WDR2 neurons often reached a plateau below 47 degrees C. Both WDR1 and WDR2 neurons had receptive fields that encompassed one or two divisions of the trigeminal nerve. 3. The T1 neuronal responses of WDR1 neurons were significantly suppressed when thermal stimuli were delivered with ISIs of 30 s. The T1 neuronal responses of WDR2 and the T2 responses of both WDR1 and WDR2 neurons were not significantly different when ISIs of 30 and 180 s were used. The T1 thresholds of WDR1 and WDR2 neurons were significantly higher when stimuli were delivered with ISIs of 30 s compared with ISIs of 180 s. 4. Most nociceptive SI neurons were located in layers III and IV of area 1-2. In a number of instances, multiple nociceptive neurons were found in the same microelectrode penetration. 5. The humans' intensity of pain sensation paralleled the neuronal responses of nociceptive SI neurons. With the use of a similar paradigm as in the monkey experiments, increases in T1 and T2 temperatures resulted in monotonic increases in pain ratings and change in pain sensation, respectively. However, the intensity of pain sensation to T1 temperatures was suppressed by ISIs of 30 s. Neither ISI produced statistically significant changes in the intensity of pain sensation to T2 stimuli. 6. These data demonstrate that manipulations that alter the intensity of pain sensation also produce concomitant changes in the responsiveness of nociceptive SI neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329362 TI - Binaural interaction in high-frequency neurons in inferior colliculus of the cat: effects of variations in sound pressure level on sensitivity to interaural intensity differences. AB - 1. Development of models of the manner in which interaural intensity differences (IIDs), the major binaural cue for the azimuthal location of high-frequency sounds, are coded by populations of neurons requires knowledge of the extent to which the IID sensitivity of individual neurons is invariant with changes in sound pressure level (SPL) and other stimulus parameters. To examine this tissue, recordings were obtained from a large sample (n = 458) of neurons with characteristic frequency (CF) greater than 3 kHz in the central nucleus of the inferior colliculus (ICC) of anesthetized cats. The sensitivity to IIDs and the effects of changes in SPL on this sensitivity were examined in neurons receiving excitatory contralateral input and inhibitory or mixed inhibitory/facilitatory ipsilateral input (EI neurons). 2. The form of an EI neuron's IID sensitivity and the effects of changes in SPL on that sensitivity were found to be determined in part by the characteristics of the neuron's rate-intensity function for monaural contralateral stimulation, and detailed rate-intensity functions were therefore obtained for 91 neurons. Many ICC neurons have nonmonotonic rate-intensity functions, the proportion so classified depending on the criterion of nonmonotonicity employed. 3. IID sensitivity functions for CF tonal stimuli were obtained at one or more intensities for 90 neurons, using a method of generating IIDs that kept the average binaural intensity (ABI) of the stimuli at the two ears constant. In the standard ABI range in which a function was obtained for each unit, the majority of EI neurons (72%) had monotonic (sigmoidal) or near monotonic IID sensitivity functions. The remainder had nonmonotonic (peaked) IID sensitivity functions, which were attributable either to mixed inhibitory and facilitatory ipsilateral influences or to the fact that the effects of ipsilateral stimulation were superimposed on nonmonotonic effects of changes in intensity at the excitatory ear. 4. IID sensitivity was examined at two or more ABIs (3-5 in most cases) for 40 neurons classified as having monotonic or near monotonic functions in the standard ABI range and for 7 neurons classified as nonmonotonic. For a small proportion of neurons with monotonic IID sensitivity functions, the form of the function was relatively invariant with changes in ABI. In those monotonic neurons in which the form of the IID sensitivity function varied with changes in ABI, the most common type of variation was that the position of the sloping portion of the function shifted systematically in the direction of larger IIDs favoring the ipsilateral ear as ABI increased.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329363 TI - Dopamine neurons of the monkey midbrain: contingencies of responses to active touch during self-initiated arm movements. AB - 1. Previous studies have shown that midbrain dopamine (DA) neurons in monkeys respond to external stimuli that are used to initiate behavioral reactions. In the present study, we investigated to what extent changes in neuronal activity would occur when behavioral acts are generated internally or whether they would depend solely on external stimuli. 2. Monkeys performed self-initiated arm movements from a resting key into a covered, food-containing box at a self-chosen moment and without external preparatory or triggering signals. In a second task, the arm movement was triggered by rapid opening of the door of the food box. This stimulus was either audible and visible or only audible to the animal. Impulses of DA neurons were recorded with movable microelectrodes from the pars compacta of substantia nigra (area A9) and areas A8 and A10 and were discriminated from those of other neurons by their long duration (1.5-5.0 ms) and low spontaneous frequency (0.5-8.5 imp/s). 3. The activity of 12% of 104 DA neurons increased slowly and moderately up to 1,500 ms before the onset of individual self initiated arm movements. Median increases amounted to 91% over background discharge rate. A further 16% of DA neurons were activated together with the onset of muscle activity and during the movement. 4. During self-initiated movements, a nonhabituating, phasic burst of impulses occurred when the monkey's hand touched a morsel of food inside the box. This response was seen in 84% of 154 neurons on the contralateral side, with median onset latency of 65 ms and duration of 160 ms. A comparable percentage of neurons responded to ipsilateral touch with similar latency and duration. 5. The touch response during self initiated movements was absent, both on the contra- and ipsilateral sides, when the animal's hand touched the bare wire normally holding the food, when touching nonfood objects, or during tactile exploration of the empty interior of the food box. Thus responses appeared to be related to the appetitive properties of the object being touched rather than the object itself. 6. In the task employing stimulus-triggered movements, 77% of 86 DA neurons discharged a burst of impulses in response to door opening but entirely failed to respond to the touch of food in the box. The response to door opening in this task was similar to the touch response during self-initiated movements in the same neurons in terms of latency, duration, and magnitude.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329364 TI - Dopamine neurons of the monkey midbrain: contingencies of responses to stimuli eliciting immediate behavioral reactions. AB - 1. This study investigates the behavioral conditions in which dopamine (DA) neurons of substantia nigra and adjoining areas A8 and A10 respond with impulses to visual and auditory trigger stimuli eliciting immediate arm- and eye-movement reactions. 2. In a formal task, the rapid opening of the door of a small, food containing box located at eye level ahead of the animal served as visible and audible trigger stimulus. Most DA neurons on the contralateral side responded to this stimulus with a short burst of impulses with median onset latency of 50 ms and duration of 90 ms (75% of 164 neurons). Similar responses were seen in a comparable fraction of DA neurons during ipsilateral task performance, suggesting that responses were not specific for the limb being used. 3. When the sensory components of the door opening stimulus were separated, DA neurons typically responded in a similar manner to the moving visual stimulus of the opening door, the low-intensity sliding noise of the opening door, and the 1-kHz sound of 90-92 dB intensity emitted from a distant source at the onset of door opening. Responses to each component alone were lower in magnitude than to all three together. 4. In a variation of the task, a neighboring, identical food box opened in random alternation with the other box but without permitting animals to reach out (asymmetric, direct-reaction go/no-go task). With each sensory component, DA neurons typically responded both to opening of go and no-go boxes. Responses were enhanced when stimuli elicited limb movements in go trials. 5. Monkeys reacted to door opening with target-directed saccadic eye movements in the majority of both go and no-go trials. Neuronal responses were equally present during the occasional absence of eye movements. Thus responses were not specific for the initiation of individual arm or eye movements. 6. Neuronal responses were absent when the same stimuli occurred outside of the behavioral task with target-direct arm and eye movements lacking. This shows that responses were not of purely sensory nature but were related to the capacity of the stimulus for eliciting behavioral reactions. 7. In a variation of the go/no-go task, an instruction light illuminated 2-3 s before door opening prepared the animal to perform the reaching movement on door opening or to refrain from moving (asymmetric, instruction-dependent go/no-go task).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329365 TI - Organizing principles for single joint movements. III. Speed-insensitive strategy as a default. AB - 1. Human subjects made discrete elbow flexions in a horizontal plane over different distances, from a stationary initial position to a visually defined stationary target 9 degrees wide. We measured joint angle, acceleration, and electromyograms (EMGs) from two agonist and two antagonist muscles. 2. Subjects made movements over four different distances following one of four different instructions. The first instructed the subject simply to choose a comfortable speed. The other three explicitly emphasized either speed, accuracy, or maintenance of the "same" speed over different distances. These instructions produced a wide range of movement velocities. 3. The initial rises of the acceleration (and therefore of the inertial torque), as well as the initial slope of the agonist EMG, were all invariant over changes in the target distance for any single instruction but were all sensitive to the given instruction. 4. Our results demonstrate that the speed-insensitive strategy is a standard or default pattern for performing movements that may be carried out for different instructions over a wide range of speeds. A uniform intensity of excitation pulse is not a byproduct of moving at maximal speed. Submaximal intensities are associated with submaximal speeds and are a selected feature of the pattern of movement control. PMID- 2329366 TI - Unit responses evoked in the amygdala and striatum by electrical stimulation of the medial geniculate body. AB - Unit activity was recorded from cells and cell clusters in the amygdala and striatum in response to electrical stimulation of the medial geniculate body (MGB) in rats anesthetized with chloral hydrate. Responses were mostly excitatory and were evoked against a relatively silent background (i.e., the units seldom fired between stimuli). The shortest latency responses were recorded in the caudate putamen (CPU), lateral amygdaloid nucleus (AL), and amygdalostriatal transition area (AST). Longer latency responses were obtained from neurons in the basolateral (ABL), basomedial (ABM), and central (ACE) nuclei of the amygdala. Moreover, while responses were evoked in AL, AST, and CPU with 300-500 microA stimuli delivered once every 10 sec, more intense and higher-frequency stimuli were required to obtain responses in ABL, ABM, and ACE. These findings are consistent with anatomical tracing studies showing that AL, AST, and CPU receive direct projections from the MGB and related acoustic processing areas of the thalamus but that ACE, ABL, and ABM do not. PMID- 2329367 TI - The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning. AB - Previous work has implicated projections from the acoustic thalamus to the amygdala in the classical conditioning of emotional responses to auditory stimuli. The purpose of the present studies was to determine whether the lateral amygdaloid nucleus (AL), which is a major subcortical target of projections from the acoustic thalamus, might be the sensory interface of the amygdala in emotional conditioning. Lesions were placed in AL of rats and the effects on emotional conditioning were examined. Lesions of AL, but not lesions of the striatum above or the cortex adjacent to the AL, interfered with emotional conditioning. Lesions that only partially destroyed AL or lesions placed too ventrally that completely missed AL had no effect. AL lesions did not affect the responses elicited following nonassociative (random) training. AL is thus an essential link in the circuitry through which auditory stimuli are endowed with affective properties and may function as the sensory interface of the amygdala during emotional learning. PMID- 2329368 TI - Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329. AB - In vitro autoradiography was performed in order to visualize cholecystokinin-A (CCK-A) receptors in sections of Cynomolgus monkey brain. CCK-A receptors were defined as those which displayed high affinity for the selective non-peptide antagonist MK-329 (L-364,718) and were detected in several regions by selective inhibition of 125I-Bolton Hunter CCK using MK-329 or direct labeling with 3H-MK 329. In the caudal medulla, high densities of CCK-A sites were present in the nucleus tractus solitarius, especially the caudal and medial aspects, and also the dorsal motor nucleus of the vagus. CCK-A sites were localized to a number of hypothalamic nuclei such as the supraoptic and paraventricular nuclei, the dorsomedial and infundibular nuclei as well as the neurohypophysis. The mammillary bodies and supramammillary nuclei also contained CCK-A receptor sites. High concentrations of CCK-A receptors were present in the substantia nigra zona compacta and also the ventral tegmental area and may be associated with dopamine cell bodies. Binding of 3H-MK-329 was also detected in parts of the caudate nucleus and ventral putamen. The detection, by autoradiographical means, of CCK-A receptors throughout the Cynomolgus monkey brain contrasts with similar studies performed using rodents and suggests differences in the density and, perhaps, the importance of CCK-A receptors in the primate as opposed to the rodent. The data suggest the possibility that CCK-A receptors may be involved in a number of important brain functions as diverse as the processing of sensory information from the gut, the regulation of hormone secretion, and the activity of dopamine cell activity. PMID- 2329369 TI - Intrinsic and extrinsic factors influencing properties and growth patterns of identified leech neurons in culture. AB - An analysis has been made of intrinsic mechanisms influencing growth patterns of 2 identified leech interneurons in tissue culture. These small cells (known as DL and VL) display unusual arborizations in the ganglion. The distinctive branching patterns resemble the letter "T" for VL and the letter "Y" for DL. DL and VL cells contain serotonin and can be identified in situ with Neutral red. 1. DL and VL cells were isolated and cultured on 2 homogeneous substrates, concanavalin A (Con A) and leech extracellular matrix extract (ECM). Individual DL and VL cells in culture retained their ability to fire in spontaneous, rhythmical bursts. The synaptic connections formed in culture were specific and differed from those made by other serotonergic neurons. 2. On both Con A and ECM the neurons sprouted to reproduce their characteristic patterns. Every DL or VL cell that grew processes on ECM developed the appropriate Y- or T-shaped pattern. On Con A, most but not all of the cells showed specific Y or T patterns. The probability of sprouting was higher on Con A than on ECM. 3. Disruption of microtubular assemblies in freshly isolated DL and VL cells by treatment with nocodazole did not affect the later outgrowth of specific patterns in culture. 4. These results provide evidence that adult DL and VL leech neurons retain intrinsic information for determining a variety of their properties in culture: In particular, they reproduce type-specific neuritic patterns in the absence of extrinsic guidance cues. Moreover, the intrinsic pattern determining mechanism is not lost after the destruction of microtubular arrays within the cytoskeleton. PMID- 2329370 TI - Serotonin immunoreactive boutons make synapses with feline phrenic motoneurons. AB - In anesthetized cats, phrenic motoneurons were intracellularly labeled with HRP. Immunohistochemistry was used to localize serotonin-like immunoreactivity that was present in numerous boutons and nerve fibers within the ventral horn of the C5 spinal segment. Immunoreactive boutons were frequently found in apposition to phrenic motoneurons, but these close contacts were more common on the dendrites than the cell body. At the electron microscope level, serotonin-immunoreactive boutons were found to make synapses with well-defined postsynaptic densities on proximal and distal dendrites of phrenic motoneurons. These results suggest that serotonin-containing neurons may directly affect the excitability of phrenic motoneurons, mainly through an input onto their extensive dendritic trees. PMID- 2329371 TI - Spatial firing properties of hippocampal theta cells. AB - Previous studies have shown that complex-spike cells, the most common cell type recorded in the hippocampus of freely moving rats, have the property of spatial firing--that is, a cell will fire rapidly only when the animal is in a particular part of its environment (O'Keefe and Dostrovsky, 1971). In the current study, we analyze the spatial firing of theta cells, the second major class of cells in the hippocampus, which are thought to correspond to nonpyramidal neurons (Fox and Ranck, 1975, 1981). Our purposes were to extend findings from earlier spatial analyses (McNaughton et al., 1983; Christian and Deadwyler, 1986), and to determine whether the spatial firing is cell specific and independent of behavior. Theta cells were recorded from rats in a cylindrical enclosure using techniques previously used for the analysis of spatial firing in complex-spike cells (Muller et al., 1987). The spatial firing patterns of individual neurons appeared as a complex surface with several regions of high and low firing. The ratio of firing from high- to low-rate regions averaged 2.5. These spatial firing patterns were smooth and reproducible, but less so than for complex-spike cells. When a cue card on the wall was moved, theta cell firing patterns remained in register with the cue. Two analyses were performed to determine whether spatial firing patterns were secondary to spatial distributions of behavior. When only locomotor data segments were selected, spatial variations were more clear-cut. In an attempt to test whether theta cells had cell-specific patterns of firing, pairs of theta cells were recorded simultaneously. On all occasions, the firing distribution for each of the cells in a pair was clearly distinctive. These findings support the conclusions that theta cell activity contains a spatial signal that is cell specific and not secondary to other firing correlates. PMID- 2329372 TI - Emergence and refinement of clustered horizontal connections in cat striate cortex. AB - Pyramidal cells in layer 2/3 of adult cat striate cortex have long, intrinsic horizontal axon collaterals within both layer 2/3 and layer 5. These collaterals form periodic "clusters" of finer axon branches that link columns of similar orientation selectivity. We have investigated the sequence of events and possible mechanisms underlying the development of these clustered intrinsic horizontal connections using a combination of neuronal tracers and intracellular staining. Small injections of fluorescent latex microspheres made during the first postnatal week (at P4-6), when examined in tangential sections, produced an even, unclustered distribution of retrogradely labeled cells up to 2 mm from the injection site. At P8, retrograde labeling extended over a larger area and clustering was discernible, primarily among the most distant labeled cells. At both P6 and P8, labeling was similar in layers 2/3 and 5, indicating that the transition from clustered to unclustered connections occurred simultaneously for cells in superficial and deep laminae. By the end of the second postnatal week (P12-15), retrogradely labeled cells were far more clustered both within and beyond the extent of P6 label; the density of labeled cells was high throughout the labeled region, but much higher within clusters. The periodicity of these nascent clusters was similar to that in the adult. Despite obvious clustering, the pattern of retrograde label observed following injections at 2-3 weeks (P12 21) differed markedly from the adult, in that the regions between clusters contained many labeled cells. Over the next 3 weeks, the connections were refined, so that by the sixth postnatal week (P36-38), regions between clusters contained very few retrogradely labeled cells and the overall pattern of retrograde label was indistinguishable from that in adults. Despite differences in postmigratory ages of neurons from the superficial and deep laminae, clustering of retrogradely labeled cells from these 2 populations was similar at all ages. Experiments in which 2-3 weeks elapsed between the time microsphere injections were made and animals were killed demonstrated that neither the initial formation of crude clusters nor their refinement was due to cell death. Instead, cluster refinement resulted from specific process elimination. When a red microsphere injection at P15 was followed by a green microsphere injection at exactly the same location on P29, the earlier injection resulted in crude clustering, as expected. Virtually all of the cells double-labeled by the later injection were within the densest clusters of label from the early injection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329373 TI - Afferent basis of visual response properties in area MT of the macaque. II. Effects of superior colliculus removal. AB - In a previous study (Rodman et al., 1989), we found that many neurons in the middle temporal area (MT) of the macaque monkey remain visually responsive and directionally selective after striate cortex lesions or cooling. In the present study, we examined the effects of superior colliculus (SC) lesions and combined lesions of striate cortex and the SC on the visual properties of MT neurons. Removal of the SC alone had no effect on the proportion of visually responsive cells, strength of direction selectivity and direction tuning, orientation tuning, receptive field size, or binocularity in MT. There was, however, a slight increase in response strength to both stationary and moving slit stimuli. In contrast to the minor effects of SC lesions alone, addition of an SC lesion to striate cortex damage abolished all visual responsiveness in area MT. The results indicate that pathways damaged by the SC lesion are not necessary for most of the properties of MT neurons found in the intact animal, although these pathways are capable of sustaining considerable visual responsiveness and direction selectivity when striate input is removed. PMID- 2329374 TI - Eye position effects on visual, memory, and saccade-related activity in areas LIP and 7a of macaque. AB - We studied the effect of eye position on the light-sensitive, memory, and saccade related activities of neurons of the lateral intraparietal area and area 7a in the posterior parietal cortex of rhesus monkeys. A majority of the cells showed significant effects of eye position, for each of the 3 types of response. The direction tuning of the light-sensitive, memory and saccade responses did not change with eye position but the magnitude of the response did. Since previous work showed a similar effect for the light-sensitive response of area 7a neurons (Andersen and Mountcastle, 1983; Andersen et al., 1985b), the present results indicate that this modulating effect of eye position may be a general one, as it is found in 3 types of responses in 2 cortical areas. Gain fields were mapped by measuring the effect of eye position on the magnitude of the response at 9 different eye positions for each neuron. The gain fields were usually planar or largely planar for all 3 types of response in both areas, indicating that the magnitude of the response usually varies linearly with both horizontal and vertical eye position. A similar observation was made previously for the gain fields of the light-sensitive response of area 7a neurons (Andersen et al., 1985b). Although gain fields sloped in all directions for the population of cells, the gain field slopes of the light-sensitive, memory and saccade responses for individual cells were usually similar. It is proposed that these eye position effects play an important role in making coordinate transformations for visually guided movement. PMID- 2329375 TI - Learning and memory is reflected in the responses of reinforcement-related neurons in the primate basal forebrain. AB - Certain basal forebrain neurons encode the learned reinforcement value of objects: they respond differentially to visual stimuli that signal availability of fruit juice (positively reinforcing) or saline (negatively reinforcing) obtained by lick responses in visual discrimination tasks. In this report we describe the rapid, learning-related changes in the responses of these neurons during the acquisition and reversal of the reinforcement contingency of a visual discrimination reversal task. The same neurons also responded differentially to novel and familiar stimuli in 2 recognition memory tasks, in which monkeys applied the learned rule that lick responses to novel stimuli elicited saline and responses to familiar stimuli elicited juice. These differential responses to novel and familiar stimuli thus reflected the reinforcement value of the stimuli. A single presentation of a novel or a familiar stimulus was sufficient to elicit a differential response which was maintained even when the stimulus had not been seen recently. The maintenance of the differential response indicates that these neurons are influenced by a durable memory for the stimuli, estimated to be 30 trials on average. These differential neurons were recorded in the substantia innominata, the diagonal band of Broca, and a periventricular region of the basal forebrain. The responses of the reinforcement-related neurons in these 3 regions were similar in most respects. These results support the conclusion that basal forebrain neurons respond to sensory stimuli that, through learning of different contingencies, signal the availability of reinforcement. We suggest that the properties of learning and memory reflected in these neuronal responses are due to afferent pathways from ventromedial regions of the prefrontal and temporal cortices and the amygdala, and that the responses of these neurons provide an enabling mechanism that facilitates the operation of diverse cortical regions in which specific sensory, motor, or mnemonic functions take place. PMID- 2329376 TI - Neuron-glia interactions of rat hippocampal cells in vitro: glial-guided neuronal migration and neuronal regulation of glial differentiation. AB - To examine neuron-glia interactions of hippocampal cells, including glial-guided neuronal migration, glial organization of neuronal positioning and neuronal regulation of astroglial differentiation, rat hippocampal tissue, harvested between embryonic day 16 (E16) and postnatal day 3 (P3), was dissociated into a single cell suspension and plated in glass coverslip microcultures (Hatten and Liem, 1981; Hatten et al., 1984). Immunostaining the cells with antibodies against the glial filament protein (AbGFP) revealed developmental stage-specific changes in the number and extent of morphological differentiation of hippocampal astroglial cells. At E16-E18, fewer than 5% of the cells were AbGFP-positive; stained cells were immature, bearing very short processes. By E19-E20, the number of stained cells increased to 15% of the total cell population. Three forms of differentiated glial cells predominated, a bipolar form bearing processes 30-50 microns, an elongated form which resembled the radial glia of hippocampus, bearing processes 120 microns in length, and a stellate form with 3 or more processes 30-50 microns in length. At P0-P3, glial morphological differentiation varied with the culture substratum; differentiated forms resembling those seen at E20 occurred on Matrigel, but not on polylysine. Quantitation of the distribution of neurons relative to AbGFP-stained glial processes revealed developmental stage specific changes in glial organization of neuronal positioning in the cultures. In cultures of E16-E18 hippocampal cells, the neurons did not preferentially associate with astroglial cells. By E19-E20, extensive neuron-glia interactions occurred, with 80-90% of the neurons being located within 5-10 microns of a glial process. In addition to their organization of neuronal positioning, E20 hippocampal astroglial cells supported extensive neuronal migration. Migrating hippocampal neurons displayed a cytology and neuron-glia cell apposition identical to that described for migrating cerebellar granule cells in vitro (Edmondson and Hatten, 1987), closely apposing their cell soma against the hippocampal glial process and moving along the glial arm by extending a thickened, leading process. Migration was seen only along highly elongated glial profiles resembling radial glial seen in vivo. The morphological differentiation of hippocampal glial cells in vitro was dependent on cell-cell interactions with neurons. In the absence of neurons, purified hippocampal astroglia had flat, undifferentiated profiles and proliferated rapidly. The addition of hippocampal neurons rapidly arrested glial growth and induced glial process extension. PMID- 2329377 TI - Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. AB - Gonadal steroids are known to influence hippocampal physiology in adulthood. It is presently unknown whether gonadal steroids influence the morphology of hippocampal neurons in the adult intact rat brain. In order to determine whether female sex hormones influence hippocampal morphology in the intact adult, we performed Golgi impregnation on brains from ovariectomized rats and ovariectomized rats which received estradiol or estradiol and progesterone replacement. Removal of circulating gonadal steroids by ovariectomy of adult female rats resulted in a profound decrease in dendritic spine density in CA1 pyramidal cells of the hippocampus. Estradiol replacement prevented the observed decrease in dendritic spine density; progesterone augmented the effect of estradiol within a short time period (5 hr). Ovariectomy or gonadal steroid replacement did not affect spine density of CA3 pyramidal cells or granule cells of the dentate gyrus. These results demonstrate that gonadal steroids are necessary for the maintenance of normal adult CA1 hippocampal pyramidal cell structure. The short time course required to observe these effects (3 d for the estradiol effect and 5 hr for the progesterone effect) implies that CA1 pyramidal cell dendritic spine density may fluctuate during the normal (4-5 d) rat estrous cycle. PMID- 2329378 TI - Pathfinding by identified growth cones in the spinal cord of zebrafish embryos. AB - The spinal cord of early (18-20 hr) zebrafish embryos consists of a small number of neurons per hemisegment. The earliest neurons are identified and project growth cones that follow stereotyped, cell-specific pathways to reach their termination sites. We have studied the pathways taken by 4 of the early neurons in order to delineate the cells and structures their growth cones encounter during pathfinding. These neurons are 3 classes of commissural neurons (CoPA, CoSA, and CoB), which have contralateral longitudinal axons, and the VeLD neuron, which has an ipsilateral longitudinal axon. These growth cones encounter a defined set of cells and structures. Commissural growth cones appear to bypass the longitudinal axons of several identified neurons, including those from contralateral commissural neurons they encounter immediately following projection from the cell bodies. In contrast, these growth cones appear to extend in association with the longitudinal axons of commissural cells after crossing the ventral midline. Another set of cells of interest are the floor plate cells, a row of cells that constitute the ventral floor of the cord. At the floor plate growth cones exhibit cell-specific behaviors which may be influenced by the floor plate. (1) The floor plate may attract specific growth cones. The CoPA, CoSA, CoB, and VeLD growth cones all extend to the floor plate while other identified growth cones do not. (2) The floor plate may mediate cell-specific turns and induce some growth cones to cross the midline while inhibiting others from doing so. The commissural growth cones extend directly under the floor plate to cross the midline and turn anterior (CoPA and CoSA) or bifurcate (CoB); the VeLD growth cone turns away from the midline and extends posteriorly. (3) The floor plate may mediate changes in the substrate affinities of growth cones. Commissural growth cones bypass longitudinal pathways before they have encountered the floor plate, but not after. The description of pathfinding by these growth cones suggests that some elements in their environment are ignored while others are not. Most interestingly, a single structure (the floor plate) may mediate multiple, cell specific effects on spinal growth cones. PMID- 2329379 TI - Immunocytochemical localization of the GABA transporter in rat brain. AB - Polyclonal antibodies were raised against the GABA transporter (GABA-Tp) purified from rat brain tissue (Radian et al., 1986) and used for immunocytochemical localization of the antigen in several rat brain areas, including the cerebellum, hippocampus, substantia nigra, and cerebral cortex. Light microscopic studies with the peroxidase-antiperoxidase and biotin-avidin-peroxidase techniques suggested that GABA-Tp is localized in the same types of axons and terminals that contain endogenous GABA, as judged by comparison with parallel sections incubated with antibodies against glutaraldehyde-conjugated GABA. However, as expected from biochemical results, different neurons differed in their relative contents of GABA-Tp and GABA; thus, GABA-Tp was relatively low in striatonigral and Purkinje axon terminals and relatively high in nerve plexus around the bases of cerebellar Purkinje cells and hippocampal pyramidal and granule cells. The GABA-Tp antiserum did not produce detectable labeling of nerve cell bodies. Electron microscopic studies supported the light microscopic observations and provided direct evidence of cellular co-localization of GABA-Tp and GABA (as visualized by the peroxidase antiperoxidase technique and postembedding immunogold labeling, respectively). The ultrastructural studies indicated the presence of GABA-Tp also in glial processes but not in glial cell bodies. The relative intensity of the neuronal and glial staining varied among regions: glial staining predominated over neuronal staining in the substantia nigra, whereas the converse was true in the cerebellum and hippocampus. The present immunocytochemical data demonstrate directly what has previously been inferred from biochemical and autoradiographic evidence: that the mechanisms for high-affinity GABA uptake is selectively and differentially localized in GABAergic neurons and in glial cells. PMID- 2329381 TI - Reaching out to each other: nurses helping nurses. PMID- 2329380 TI - Distinct patterns of expression of two VAMP genes within the rat brain. AB - VAMPs are synaptic vesicle-specific proteins composed of a carboxy-terminal hydrophobic membrane anchor and an approximately 100 amino acid domain oriented towards the cytoplasm. In rat, two 77% homologous VAMP genes are expressed in the CNS. To precisely localize the neurons expressing these 2 forms of VAMP, we have used RNA blotting and in situ hybridization histochemistry with RNA probes specific for the 3' untranslated regions of the transcripts. These experiments revealed that the 2 genes are expressed in distict, but slightly overlapping, patterns in the rat brain. VAMP-1 expression is localized to a limited number of nuclei, particularly those involved in modulating somatomotor functions, while VAMP-2 expression is more ubiquitous, being found in nuclei associated with autonomic, sensory, and integrative roles. These data suggest that the specific structural features of individual VAMPs may play an important role in synaptic vesicle metabolism. PMID- 2329382 TI - Humor: a teaching strategy to promote learning. AB - Staff development educators strive to identify methods to facilitate learners' receptivity to information presented, willingness to explore new ideas, and ability to analyze relationships among concepts. This article focuses on the value of humor as a teaching strategy and suggests methods for its incorporation into educational offerings. A "Humor Profile" is provided to give nurse educators an indication of the degree to which they need to improve their use of humor as a teaching strategy. PMID- 2329383 TI - A review of patient education in nursing. AB - Patient education by nurses makes a substantial contribution to patients' health and wellness. Nursing studies document patient benefits resulting from patient education. Studies indicate that some patients have fewer symptoms from their illnesses after patient education, whereas other chronically ill patients experience fewer hospitalizations. To date, most benefits have been empirically observed rather than scientifically documented. To determine the extent to which patient education contributes to health improvement, studies need to focus on measurable long-term benefits that can be translated into cost-effectiveness. Nurses are encouraged to demonstrate the value of patient education with documentation of its effects on patient health. PMID- 2329384 TI - Developing a psychiatric self-instruction module. AB - The development of a psychiatric assessment self-instructional module that incorporated learning needs assessment, collaboration, implementation, and evaluation is described. A tool as flexible as a self-instructional module responds to various learning styles and is adaptable to continuing education needs. PMID- 2329386 TI - A multi-faceted critical care program. PMID- 2329385 TI - Creating a flexible learning environment. AB - Lack of classroom space is a common problem for many hospital-based nurse educators. This article describes how nursing educators in one institution redesigned fixed classroom space into a flexible learning center that accommodates their various programs. Using the nursing process, the educators assessed their needs, planned the learning environment, implemented changes in the interior design, and evaluated the outcome of the project. The result was a learning environment conducive to teaching and learning. PMID- 2329387 TI - Effect of vitamin E on linoleic acid-mediated induction of peroxisomal enzymes in cultured porcine endothelial cells. AB - Linoleic acid decreases endothelial barrier function in culture. We hypothesize that the mechanism may involve induction of peroxisomes, with subsequent generation of hydrogen peroxide, and that vitamin E may protect against barrier function loss by preventing the induction of peroxisomal enzymes. To investigate this hypothesis, we exposed cultured endothelial cells to 0 or 90 mumols/L linoleic acid [18:2(n-6)], with or without 25 mumols/L supplemental vitamin E, for 5 d. The induction of peroxisomes by linoleic acid exposure was determined by measuring cellular peroxisomal beta-oxidation and catalase activity. Vitamin E alone had no effect on beta-oxidation or catalase activity, whereas linoleic acid exposure significantly increased both compared with control values. Vitamin E supplementation prevented induction of peroxisomal beta-oxidation and catalase activity by 18:2. In contrast, cell enrichment with vitamin E had no effect on 18:2-induced accumulation of cytoplasmic lipid-like droplets. These results confirm our hypothesis that the protective effects of vitamin E against fatty acid-mediated endothelial cell injury may be due in part to the ability of vitamin E to prevent the induction of peroxisomal beta-oxidation enzymes and thus the formation of excess hydrogen peroxide. PMID- 2329388 TI - Long-chain fatty acid composition of maternal liver lipids during pregnancy and lactation in the rat: comparison of triglyceride to phospholipid. AB - The change in long-chain fatty acid composition in maternal liver was studied during pregnancy and lactation in the rat. Maternal liver triglycerides and phospholipids transiently accumulated and were depleted of long-chain fatty acids during pregnancy and lactation. During pregnancy, maternal liver accumulated triglyceride, but triglyceride fatty acid composition changed little. However, maternal liver total phospholipid fatty acid composition changed significantly without a change in the total pool size throughout pregnancy or lactation. The change in composition of (n-3) and (n-6) essential fatty acids in maternal liver triglyceride and total phospholipid occurred in an apparently dyssynchronous manner throughout pregnancy and lactation. PMID- 2329389 TI - Effects of foods rich in polyphenols on nitrogen excretion in rats. AB - The extent to which tea, cocoa and carob (foods rich in polyphenols) influence fecal nitrogen (N) excretion was investigated in rats. The studies took into account the methylxanthine contents of tea and cocoa as well as the poor digestibility of cocoa nitrogen. Balance measurements indicated that all three food sources significantly increased fecal nitrogen excretion relative to methylxanthine-matched control diets (p less than 0.01). In the case of cocoa, virtually all the increase could be attributed to the poor digestibility of cocoa protein itself (estimated to be only 28-30% of total N in cocoa powder). There appeared to be no other effects. With extracts of tea and carob, however, the increased excretion of N in feces resulted either from a decreased digestibility of other dietary protein, through interaction with their polyphenols, or from a stimulation of the excretion of endogenous (body) nitrogen. With respect to the latter possibility, a preliminary investigation with the stable isotope of nitrogen (15N) showed that tea produced a marked increase in the excretion of endogenous nitrogen. These studies, therefore, indicate that foods rich in polyphenols have varying effects on N excretion in feces and that, in the case of tea at least, the loss of endogenous nitrogen may be a major contributing factor. PMID- 2329390 TI - Studies of the reversible binding of biotin to human plasma. AB - In this study we sought to determine the extent of the reversible binding of [3H]biotin to macromolecules (presumably proteins) of human plasma under physiologic conditions during physiologic time intervals ranging from minutes to days. Fresh, heparinized human plasma and [3H]biotin were incubated in 5% CO2, 95% N2 at 37 degrees C. After reaching equilibrium, free biotin was separated from bound biotin by centrifugal ultrafiltration (1500 x g for 60 min) using membranes with a molecular weight cutoff of 30,000. In a sample from a single individual, we detected a mean retentate:ultrafiltrate ratio of 1.20 +/- 0.03 (mean +/- SD, n = 14 determinations). In a group of 10 healthy adults, the mean retentate:ultrafiltrate ratio was 1.17 +/- 0.02; thus, approximately 8% of the biotin in the combined pool of free and reversibly bound biotin is bound. No consistent change in retentate:ultrafiltrate ratio was detected for total biotin concentrations ranging between 500 fmol/mL and 2 nmol/mL, but the ratio decreased to 1.1 at 400 nmol of biotin per mL. Thus, the biotin-binding system of human plasma appears to be a low affinity, high capacity system. A similar biotin binding system was detected in experiments with purified human serum albumin. These results provide evidence that the majority of added [3H]biotin does not bind to plasma protein under physiologic conditions. To the extent that added [3H]biotin can be assumed to reflect reversible binding of endogenous unlabeled biotin, we infer that endogenous, reversibly bound biotin can account for no more than one-tenth of the increase in biotin detected after acid hydrolysis of plasma. PMID- 2329391 TI - Qualitative and quantitative assessment of flavins in cow's milk. AB - Although milk is one of the primary sources of riboflavin in the North American diet, the amounts of riboflavin and other flavin derivatives in milk have not been accurately quantified. In this study, a comprehensive assessment of milk was performed to identify and quantify greater than 95% of the flavins in this food. Riboflavin and flavin adenine dinucleotide (FAD) were the predominant flavins in all milk samples; 10-(2'-hydroxyethyl)flavin was next most common. The latter is potentially an antivitamin that may exert its effect at either the absorption or utilization level. Therefore, the presence of this analog should be considered when evaluating the riboflavin efficiency of milk. The large quantity of FAD indicates that precautions against underestimating FAD are warranted when determining total flavin content by fluorescence. This is particularly important because the fluorescence of FAD at pH 7.0 is only 10-20% of that for riboflavin. The presence of 7 alpha-hydroxyriboflavin (7-hydroxymethylriboflavin) in milk was ascertained by extensive testing. Traces of 8 alpha-hydroxyriboflavin (8 hydroxymethylriboflavin) were also detected. These metabolites may serve as indicators of cellular biochemical activity. PMID- 2329392 TI - Milk consumption and zinc retention in postmenopausal women. AB - We measured intestinal 65Zn absorption and whole-body retention in postmenopausal women following a meal extrinsically labeled with 65Zn. The meal was consumed with 200 mL of milk or with a calcium phosphate supplement. Fifteen elderly (mean age 69) subjects were studied during three 12-d experimental periods in which they were fed either a basal diet containing 16 mg Zn or the basal diet supplemented either with 400 mL of milk or with dibasic calcium phosphate supplements containing an equivalent amount of calcium (468 mg) and phosphorus (360 mg). Measurements of fractional zinc absorption were made in 9 of the 15 subjects by a dual-isotope technique using 65Zn and 51Cr (as nonabsorbable fecal markers). Fractional zinc absorption was 0.22 +/- 0.06 (mean +/- SEM) after the standard meal, 0.23 +/- 0.06 with added milk and 0.22 +/- 0.03% with the added calcium phosphate supplement. The corresponding values for 65Zn retention in 15 subjects 12 d after dosing were 0.10 +/- 0.01% for all treatments. No significant effect of milk or calcium phosphate supplementation was observed on either 65Zn absorption or retention. We conclude that increased milk consumption with meals has no detrimental consequences on zinc nutriture in elderly women. PMID- 2329394 TI - Causes, location, and timing of relapse following rigid fixation after mandibular advancement. AB - The purpose of this study was to evaluate two different groups of patients who underwent bilateral sagittal split osteotomy for mandibular advancement. One group demonstrated no relapse, whereas a second group had documented relapse. The following questions were asked: 1) What factors contribute to relapse? 2) At what site in the mandible is movement seen? and 3) During what period does movement occur? A retrospective lateral cephalometric serial analysis was performed on 50 patients at multiple time intervals. Criteria for a candidate include 1) mandibular advancement surgery with rigid fixation, with or without genioplasty, 2) no maxillary surgery, and 3) relapse of 25% or more of the advancement. Of the 50 patients analyzed, 13 (26%) showed relapse of 25% or more and served as the relapse group. Twelve patients showed no relapse and served as the comparison group. Multiple-regression analysis for the relapse group showed that magnitude of advancement, increasing gonial arc and changing mandibular plane significantly accounted for 84.9% of the variance observed in relapse (P less than .001). Repeated-measures ANOVA showed that the majority of relapse occurred in the first 6 weeks after surgery (68%, P less than .05). Results of a paired t test showed that a significant change occurred in all the linear and angular measures except SN-AR-GO (P less than .05). PMID- 2329393 TI - Effects of a chlorhexidine gluconate oral rinse on the incidence of alveolar osteitis in mandibular third molar surgery. AB - Alveolar osteitis (dry socket) continues to be a frequent sequela of third molar surgery. Chlorhexidine 0.12% used as an oral rinse has been reported to reduce the incidence of dry socket. This study compares the effectiveness of 0.12% chlorhexidine used as a preoperative rinse and immediate postextraction irrigant with 1) similarly used 0.05% cetylpyridium, preoperative chlorhexidine rinse and postextraction saline irrigation, and 2) only postextraction irrigation with normal saline in the reduction of alveolar osteitis in mandibular third molar extractions. The results indicate that chlorhexidine and cetylpyridium were no more effective in the reduction of alveolar osteitis than postextraction irrigation with normal saline. PMID- 2329395 TI - Morphologic differences between superior and inferior disc surfaces in chronic internal derangement of the temporomandibular joint. AB - This study examines the morphologic differences between the superior and inferior disc surfaces in patients with chronic internal derangement of the temporomandibular joint. Forty-two discs were removed in 33 patients when morphologic or qualitative tissue changes made a reparative procedure impossible. Eighty-three percent of the joints operated in this series showed late opening (grade III) clicking or were considered clinically locked. Specific differences between superior and inferior disc surface anatomy were demonstrated in these cases of long-standing internal derangement. PMID- 2329396 TI - A comparative in vitro study of fixation of mandibular fractures with paraskeletal clamps or screw plates. AB - The use of porcine rib pairs as an in vitro analog for the edentulous mandible is described. Using this model, the relative degree of fixation achieved with a screw plate (Champy) and a paraskeletal clamp plate (Mennen) has been evaluated. The fractured plated ribs failed at significantly lower bending forces than the non-sectioned controls. However, no statistically significant difference in force at failure between the two different methods of plate fixation could be demonstrated. PMID- 2329397 TI - Adaptive remodeling of the rabbit temporomandibular joint following discectomy and dietary variations. AB - This study evaluates the healing of the rabbit temporomandibular joint (TMJ) following discectomy in four groups of animals fed a ground diet for 3 consecutive months (group 1), a ground diet for 1 month followed by 2 months of a coarse diet (group 2), a ground diet for 6 consecutive months (group 3), or a ground diet for 3 months followed by a coarse diet for 3 months (group 4), in order to evaluate the effects of changing the diet texture following discectomy. After 3 and 6 months, histologic evaluation demonstrated that 1) an early hyperplastic response in the fibrocartilage regressed in the later period regardless of diet, and 2) switching the ground diet to a hard diet caused degenerative scores to increase after both 1 and 3 months. PMID- 2329398 TI - Increased osteogenesis in alveolar wound healing elicited by demineralized bone powder. PMID- 2329399 TI - Perforation into middle cranial fossa as a sequel to use of a Proplast-Teflon implant for temporomandibular joint reconstruction. PMID- 2329400 TI - Superior orbital fissure syndrome and bilateral internal carotid pseudoaneurysms. PMID- 2329401 TI - Cavernous hemangioma of the zygoma: report of cases. AB - Osseous hemangiomas of the facial bones are rare lesions, with most cases occurring in the maxilla and mandible. Reported cases in the zygoma are sparse. Two cases of zygomatic hemangiomas with widely differing presentations are reported. One case in a neonate required surgery to prevent fatal hemorrhage, and the other in an adult required correction of a cosmetic deformity. Each patient presented with a second congenital anomaly. Therapeutic problems associated with these lesions and their management are discussed. PMID- 2329402 TI - Angiolipoma of the cheek: report of a case. PMID- 2329403 TI - Squamous cell carcinoma of the temporomandibular joint: report of a case with long-term follow-up. PMID- 2329404 TI - Massive maxillary ameloblastic fibro-odontoma: case report with surgical management. PMID- 2329405 TI - The Luomanen oral airway and endotracheal tube holder as an aid to pediatric fiberoptic endoscopy. PMID- 2329406 TI - Modified Boley gauge for use as a reference plane in orthognathic surgery. PMID- 2329407 TI - Article or editorial: who nose? PMID- 2329408 TI - Becoming an expert in oral implantology. PMID- 2329409 TI - Bone induction in primates by demineralized bone matrix. PMID- 2329410 TI - Where have all the clickers gone? PMID- 2329411 TI - Evidence that production of autoantibody to the alternative pathway C3 convertase is a normal physiologic event. AB - The origin of autoantibody production was studied with the use of antibody to the alternative pathway C3 convertase (C3 nephritic factor (C3NeF), as a model. Pokeweed mitogen stimulation of peripheral mononuclear cells from newborn infants, normal adults, and patients with membranoproliferative glomerulonephritis indicated that the ability to make C3NeF is apparently present in everyone from the time of birth. In addition, C3NeF appeared to express a single or very limited idiotope (21/21 isolates). The data also suggest that the elaboration of C3NeF may approximate an antibody response after immunization. Thus the C3NeF fraction of the total IgG or IgM produced in culture by pokeweed mitogen-stimulated mononuclear cells from normal neonates and adults, as well as from patients, was in the range of the production of specific antibody. Further, both IgG and IgM C3NeF produced by cells from these normal individuals, including newborn infants, had an affinity for antigen (10(8) to 10(9) L/mol) that was also in the range of specific antibody. Most of the autoantibody molecules (5/7) from serum were IgG3; two B cell clones producing C3NeF were CD5-negative. These experiments indicate that unmutated germline genes are used in the production of C3NeF and that a limited spectrum of antiidiotypic antibodies regulate its production. PMID- 2329412 TI - Membranoproliferative glomerulonephritis: the Cincinnati experience--cumulative renal survival from 1957 to 1989. AB - Seventy-six children with idiopathic MPGN have been followed at this medical center since 1957 (mean 10.6 years of disease). Seventy-one of the children have been treated with a regimen of prednisone (mean 7.7 years of treatment). Monotherapy with alternate-day prednisone was used in 50 of the children. Other immunosuppressive and cytotoxic drugs have not been used since 1981. In the 71 treated patients, the cumulative renal survival (creatinine less than 3.0 mg/dl (265.5 mumol/L)) was 82% in the tenth year and 56% in the twentieth year after disease onset. Cumulative renal survival, calculated from the date of initiation of the prednisone regimen, was 75% in the tenth year and 59% in the twentieth year. As our experience with this disease has increased, long-term cumulative renal survival has improved. PMID- 2329413 TI - Relation of urinary tract infection and vesicoureteral reflux to scars: follow-up of thirty-eight patients. AB - A prospective study compared the outcome of vesicoureteral reflux and recurrent urinary tract infections in children (3 boys, 62 girls) who received medical prophylaxis or underwent surgical correction of reflux. Thirty-eight children returned for reevaluation 6 to 13 years (average 9.5 years) after entry. There was a marked decrease in prevalence and severity of reflux. At entry, 13 had significant scarring that had progressed at follow-up. New scars were documented by dimercaptosuccinic acid scan at follow-up in eight children on the medical regimen and two who were initially treated with surgical correction of reflux. Four patients with high-grade sterile reflux were followed for 6 to 10 years without the development of cortical scars. Our data support the role of urinary tract infection and vesicoureteral reflux, but not sterile reflux, in the pathogenesis of chronic pyelonephritis and reflux nephropathy. PMID- 2329414 TI - Regional variation in C4 phenotype in patients with IgA nephropathy. AB - The relationship between complete deficiency for either isotype of the fourth component of complement, C4A or C4B, and glomerulonephritis was initially examined in white patients from Kentucky with either IgA nephropathy or Schonlein Henoch purpura. Subsequently, C4B deficiency was found to be associated with IgA nephropathy for pediatric patients followed in Cincinnati, Ohio. We later reported that at least 60% of the original patients from Kentucky were related to at least one other patient with the disease. This finding raised the possibility that the C4 phenotype frequencies for these patients may have been biased by the fact that they were based on a sample of related patients. In our study, C4 phenotyping was performed for 52 related and 63 unrelated patients from Kentucky, 81 unrelated patients from the Mid-South region of the United States, and 39 unrelated patients from the Puglia region of southeastern Italy. In addition, data from patients with IgA nephropathy from Spain were available for comparative studies. Neither C4A deficiency nor C4B deficiency was significantly increased for groups of unrelated patients from the Mid-South, Italy, Spain, or Kentucky in comparison with regional control subjects. In fact, C4A and C4B deficiencies did not occur in any of the Italian patients. With the exception of C4A.6, frequencies for the most common C4A and C4B alleles did not differ among the unrelated patient and control groups from Kentucky and the Mid-South. In addition, no significant differences in C4A and C4B allelic frequencies were observed in comparisons of pediatric patients (diagnostic biopsy before age 18 years) and adult patients with IgA nephropathy in either U.S. population. Italian control subjects had a significantly lower frequency for C4A null alleles in comparison with control subjects from both Kentucky and the Mid-South; a significantly higher frequency of C4B null alleles was found among Kentucky control subjects than in Mid-South, Italian, and Spanish control samples. The importance of recognizing the ethnic background of study subjects and of eliciting a good family history to minimize unsuspected sampling of related patients should be considered in future disease association studies. PMID- 2329415 TI - Autoantibody to complement neoantigens in membranoproliferative glomerulonephritis. AB - With the exception of C3 nephritic factor, autoantibody formation has not been commonly associated with membranoproliferative nephritis (MPGN). We measured autoantibodies (nephritic factors) to the C3 convertases C3bBb (NFa) and C3bBbP (NFt), which result in fast and slow C3 activation, respectively, and to a neoantigen on C1q fixed to a solid phase (spC1q) in sera from 29 patients with MPGN type I, 26 with type II, and 28 with type III. Autoantibody formation was common in all MPGN types. An autoantibody to a C3 convertase neoantigen was identified in more than 75% of the hypocomplementemic MPGN sera tested. Anti C3bBb (NFa) was present in 81% of patients with MPGN type II but was rarely found in either type I or type III. Anti-C3bBbP (NFt) was common in both MPGN I and III. Anti-spC1q was present in 74% of patients with type I and in 38% and 48% of types II and III MPGN, respectively. Patients with MPGN types I, II, and III had one and two serum autoantibodies detected significantly more frequently than did a group of healthy subjects. The presence of any one autoantibody was not specifically associated with the presence of any other autoantibody. The results indicate that multiple autoantibody formation is common in all MPGN types. MPGN II, and possibly MPGN I, tend to form more specific autoantibodies. PMID- 2329416 TI - Formulas for older infants. AB - We explored the possibility that standard infant formulas designed as the sole source of nutrients for small, rapidly growing infants may not be equally suitable for older, larger, and less rapidly growing infants who obtain a portion of energy intake from beikost. Our approach was to consider the probable nutrient intakes of a 6-month-old hypothetic infant receiving 80% of energy intake from a standard formula and 20% from beikost, and nutrient intakes of a 10-month-old hypothetic infant receiving 50% of energy intake from a standard formula and 50% from beikost. The assortment of beikost items consumed by infants is moderately high in protein and low in fat. Calculated nutrient intakes of the 10-month-old hypothetic infant were compared with intakes of infants of similar age in two national surveys. We conclude that standard infant formulas designed for young infants are reasonably well suited to meeting the nutrient needs of infants during the latter half of the first year of life. PMID- 2329417 TI - Respiratory virus infection as a cause of prolonged symptoms in acute otitis media. AB - We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment. PMID- 2329418 TI - Electrophysiologic studies, computed tomography, and neurologic outcome in acute bacterial meningitis. AB - To determine the value of computed tomography and electrophysiologic studies in predicting neurologic outcome, we prospectively studied 41 children with acute bacterial meningitis, using clinical examination, computed tomography of the head, electroencephalography, brain-stem auditory evoked response, and visual evoked potential mapping during the acute illness. Two children died; 32 of the remaining 39 children were reviewed clinically, electrophysiologically, and with computed tomography between 5 and 38 months after the illness. The electrophysiologic data obtained during the illness were not found to alter the acute-stage management. Focal or generalized suppression, demonstrated on the electroencephalogram, was associated with a poor outcome. Cerebral infarction and edema, demonstrated by computed tomography of the head, were predictive of a poor outcome, but enlarged ventricular and subarachnoid spaces and increased subdural effusions were of no predictive value. Neither computed tomographic scans nor electrophysiologic data were better indicators of neurologic prognosis than the clinical examination. PMID- 2329420 TI - Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness. AB - We present a novel condition, designated as a primary disorder of vigilance, that has symptoms which overlap those of attention deficit-hyperactivity disorder. Vigilance is the state of being watchful, awake, and alert. When vigilance is lost, the individual has difficulty sustaining attention. The most obvious evidence of lowered vigilance is motor restlessness (fidgeting and moving about, yawning and stretching, talkativeness, or a combination of these) to improve alertness when sitting or standing still or when involved in tasks requiring continuous mental performance. When prevented from being active to stay awake, persons with lowered vigilance will stare off, daydream, show minor hyperactivity, and finally may fall asleep. They will also have decreasing attention to current activities and usually avoid or lose interest in structured or repetitive activities (complaining of boredom and monotony). The primary disorder of vigilance (for which criteria have been established) is a dominantly inherited condition with onset in early childhood and worsening symptoms with age. Persons with the primary disorder of vigilance have a remarkably kind and caring temperament. When untreated this disorder can cause chronic failure at school and work, but when properly recognized it responds well to treatment with stimulant medication and schedules that avoid sameness and repetition. PMID- 2329419 TI - Protection of breast-fed infants against Campylobacter diarrhea by antibodies in human milk. AB - To investigate the role of breast-feeding in preventing diarrhea caused by Campylobacter jejuni, we followed 98 Mexican children prospectively for 2 years beginning at their birth. Attack rates of diarrhea in children less than 6 months of age who were not fed human milk were 2.3 times greater than those in children of the same age who were fed human milk. Breast-fed children remained free of diarrhea for a longer time than non-breast-fed children (p less than 0.0005). The diarrhea attack rate caused by C. jejuni for non-breast-fed infants was significantly greater (p less than 0.005) than that in the breast-fed group. Secretory IgA milk antibody titers against glycine acid-extractable antigen of C. jejuni were high in colostrum, decreased during the first month of breast feeding, and generally persisted throughout lactation. Human milk consumed by children in whom Campylobacter diarrhea developed did not contain secretory IgA antibodies to the glycine acid-extractable common antigen of Campylobacter. This study shows an association between Campylobacter antibodies in human milk and prevention of diarrhea caused by Campylobacter. PMID- 2329421 TI - Prospective evaluation of aluminum loading from formula in infants with uremia. AB - Assessment of potential aluminum loading from regular ingestion of a commercial infant formula (Similac PM 60/40), as the only milk substitute, was made in 14 infants aged 9.6 +/- 4.4 months who were also undergoing continuous cycling peritoneal dialysis. Tissue aluminum accumulation was assessed by serial measurements of plasma aluminum levels, from the increment in plasma aluminum after a standardized deferoxamine infusion, and from quantitative histomorphometry of bone and measurements of total bone aluminum content. Initial mean plasma aluminum levels were 0.61 +/- 0.32 mumol/L, (normal 0.30 +/- 0.04 mumol/L), and values were less than 0.92 mumol/L during the follow-up of 20 +/- 8 months. Plasma aluminum levels increased from 0.59 +/- 0.18 to 0.88 +/- 0.22 mumol/L after a single dose of deferoxamine. The histochemical stain for bone aluminum was negative for all patients, and the bone aluminum content was 0.27 +/ 0.22 mmol/kg dry weight (normal 0.08 +/- 0.04 mmol/kg dry weight). Thus the infant formula Similac PM 60/40 can be safely used in infants with chronic renal failure. PMID- 2329422 TI - Cancer in the child infected with human immunodeficiency virus. PMID- 2329423 TI - Relationship of fever magnitude to rate of serious bacterial infections in neonates. PMID- 2329424 TI - Treatment outcome in children with malignancies associated with human immunodeficiency virus infection. PMID- 2329425 TI - Bacterial contamination rate of urine collected in a urine bag from healthy non toilet-trained male infants. PMID- 2329426 TI - Hydronephrosis caused by ureteric obstruction in chronic granulomatous disease: successful treatment by percutaneous nephrostomy and antibiotic therapy. PMID- 2329427 TI - Bilateral breast masses and bloody nipple discharge in a 4-year-old boy. PMID- 2329428 TI - Biotinidase deficiency in black children. PMID- 2329429 TI - Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5 fluorocytosine in neonates. AB - To determine the pharmacokinetics of amphotericin B and 5-fluorocytosine in neonates, we measured serum concentrations at first dose and after 5 days of therapy by high-performance liquid chromatography in 13 neonates (mean birth weight 1.2 +/- 0.8 kg). The dose of amphotericin B was serially increased from 0.1 to 0.5 mg/kg/day in 10 infants but was decreased from 0.8 to 1.0 to 0.5 mg/kg/day in three infants. Amphotericin B concentrations were not detectable in infants receiving 0.1 mg/kg/day. Amphotericin B cerebrospinal fluid concentrations were 40% to 90% of serum values obtained simultaneously. Serum concentrations after oral administration of 5-fluorocytosine (dose 25 to 100 mg/kg/day) were detectable in all infants. We found extreme interindividual variability for the half-life, volume of distribution, and clearance for both drugs. Four infants had minimal elimination for both drugs between doses, a finding that correlates with rises in serum creatinine (greater than 0.4 mg/dl, 40 mumol/L) and blood urea nitrogen (greater than 10 mg/dl, 3.6 mmol/L). We recommend that the dose of amphotericin B given on the first day of treatment be greater than the usual testing dose of 0.1 mg/kg/day. We also recommend an initial 24-hour dosing interval for amphotericin B and 5-fluorocytosine. Serum drug concentrations may need to be monitored in high-risk, low birth weight infants. PMID- 2329430 TI - Influence of early feeding style on adiposity at 6 years of age. AB - In a previous study we found that a vigorous infant feeding style measured in the laboratory at 2 and 4 weeks of age predicted the degree of adiposity at 1 and 2 years of age. A follow-up of this cohort of infants at 3 and 6 years of age is now reported. Factors predicting adiposity, measured by body mass index at 3 years of age, were pressure of suckling, with high-pressure sucking (denoting a vigorous feeding style) associated with greater adiposity, and time of introduction of solid food, with delayed introduction of solid food or breast feeding longer than 5 months, or both, being associated with greater adiposity. Predictive factors at 6 years of age were adiposity at birth, with greater adiposity at birth predicting greater fatness at 6 years, parental education, with less education associated with fatness, and a prolonged period of breast feeding with delayed introduction of solid food. These factors accounted for 40.4% of the variance in adiposity at 3 years of age and 31.2% at 6 years. The effects of social learning on body mass index, indicated by parental educational level, appear to strengthen over time, whereas the effects of the vigorous feeding style wane. PMID- 2329431 TI - Health risk behaviors and attempted suicide in adolescents who report prior maltreatment. AB - We hypothesized that high school students who experienced prior maltreatment would be more likely than their peers to report health risk behaviors and suicide attempts. Before the establishment of a high school-based clinic, an anonymous needs assessment survey was completed by 600 adolescents (grades 9 to 12). Sociodemographic information was obtained and questions were asked about physical and sexual abuse, health-related behaviors and habits, and suicide attempts. Thirteen percent of the adolescents had been maltreated: 5.2% reported prior physical abuse, 5.4% sexual abuse, and 2.7% both physical and sexual abuse. Multivariate statistical techniques were used to clarify how previous abuse was related to adolescent risk-taking behaviors and suicide. Students with a history of physical abuse were three times more likely than non-abused peers to drink alcohol and smoke cigarettes, almost twice as likely to use illicit drugs, six times more likely to self-induce vomiting, and five times more likely to attempt suicide. A student with a history of prior sexual abuse had a three and one-half times greater chance of being sexually active and was more than three times more likely to attempt suicide. These data on a nonclinical, nondeviant population of adolescents indicate that physical or sexual abuse in childhood may have a significant impact on adolescent health risk behaviors and suicide attempts. PMID- 2329432 TI - Genitalia in human figure drawings: childrearing practices and child sexual abuse. AB - To replicate and explore the associations of drawing genitalia on a human figure, child-rearing practices, and a history of alleged sexual abuse, we designed a cross-sectional study of 109 alleged child sexual abuse victims, ages 3 through 8 years, and a group of 109 comparison children matched for age, sex, race, and socioeconomic status but with no history of abuse. A standardized format was used to collect drawings, administer the Peabody Picture Vocabulary Test, and gather background data on medical, developmental, and child-rearing issues. Seven alleged sexual abuse victims and one comparison child spontaneously drew genitalia (p = 0.02, one-tailed Fisher Exact Test, estimated relative risk 7.96). No differences in drawing maturity (Draw-A-Man score) were identified, although Peabody Picture Vocabulary Test scores were higher in comparison children (82.1 vs. 91.0, p less than 0.01). Neither drawing genitalia nor history of alleged sexual abuse were significantly associated with histories of medical problems, enuresis, encopresis, urinary tract infection, or child-rearing practices related to sleeping, nudity, bathing, sexual abuse education, or exposure to sexually explicit materials. The similar patterns of child-rearing practices in both samples should make professionals cautious in attributing allegations of abuse to specific child-rearing practices. This study confirms our previous report that the presence of genitalia spontaneously drawn on a child's drawing of a human figure is associated with alleged sexual abuse. PMID- 2329433 TI - Women and the future of academic pediatrics. PMID- 2329434 TI - Thrombocytosis in hospitalized children. PMID- 2329435 TI - Hyponatremia and seizures during desmopressin acetate treatment in hypothyroidism. PMID- 2329436 TI - Diagnosis of pneumonia in immunocompromised patients. PMID- 2329437 TI - Type II errors. PMID- 2329438 TI - Drug interactions affecting theophylline clearance. PMID- 2329439 TI - Indomethacin and ischemic brain injury in neonates. PMID- 2329440 TI - Hypoalbuminemia in young infants with cystic fibrosis. PMID- 2329441 TI - Noncutaneous abnormalities with hypomelanotic nevi. PMID- 2329442 TI - Preparation, characterization and performance evaluation of neomycin-HSA microspheres. AB - Human serum albumin microspheres containing neomycin sulphate were prepared using emulsion polymerization and polymer dispersion techniques. The many variables which may affect the shape, size, stability, release of the drug from the microspheres such as internal phase to external phase volume ratio, human serum albumin content, stirring rate, polymer content and stabilizing agent concentration, were studied. Unlike the microspheres prepared by the emulsion polymerization technique, polymer dispersion stabilised microspheres were uniform in size and shape with a narrow range of size distribution. In vitro release of neomycin sulphate from albumin microspheres was studied using the dialysis cell method. The drug release from microspheres followed Q versus (t)-1/2 linear relationship. The in vivo distribution studies on prepared microspheres revealed that the localization takes place preferably in lung tissues, liver, spleen and kidney and is found to be dependent on the microsphere size. On administration of microspheres of 3-6 microns size, approximately 55 per cent of administered drug could be localized in the lungs. PMID- 2329444 TI - Electrostatic interaction of microcapsules with guinea-pig polymorphonuclear leucocytes. AB - Electrostatic interaction of microcapsules with guinea-pig polymorphonuclear leucocytes was investigated at different ionic strengths of the medium through measurements of the degree of phagocytosis by the cells of microcapsules. At any ionic strength, the interaction exhibited a maximum when the surface potential of microcapsules was equal to that of the leucocytes to make phagocytosis of microcapsules by the cells minimum. The experimental findings were analyzed by a novel model for the electrostatic interaction between ion-penetrable membranes. In this analysis, it was assumed that the leucocytes have an area (or areas) which permits cations to partition much more into the membrane than anions on their surface to reduce the electric potential of the area. PMID- 2329443 TI - Application of encapsulated enzyme dispersed in a continuous stirred tank reactor. AB - An application of encapsulated lipase to the hydrolysis of triacetin (triglyceride of acetic acid) was carried out with a continuous stirred tank reactor, in which the encapsulated enzyme was dispersed. An automatic control device to control pH of the reaction mixture at a desired level was designed and installed in the reactor system. Conversion of triacetin at the steady state operation with pH controlled became significantly higher than that without pH control. A particular kinetic model proposed by the authors, which regarded the mass-transfer through the wall of microcapsules as a dominant resistance to the overall reaction rate, was also applicable to simulate the behaviour of CSTR system as in the case of packed-bed reactor. PMID- 2329445 TI - Release kinetic study of RHPC coated aspirin microcapsules. AB - The present communication deals with the study of the effect of pH on the drug release characteristics and the drug release kinetic from the RHPC (Rosin Hard Paraffin Combination) coated aspirin microcapsules. For the purpose of the present study the aspirin microcapsules were prepared by pan coating method imparting 15 coats using 10 per cent RHPC solution in acetone. A standard coating procedure was used to coat the aspirin granules. Dissolution studies were carried out in media with different pH. To get a clear picture drug release studies were conducted in each media for 3 h. The results showed that the RHPC films were resistant to acidic pH releasing less than 5 per cent and 15 per cent drug in 3 h in pH 1.2 and 3.0 respectively. The T 50% in pH 5.0 media was 163 min. The drug was released very quickly in pH 7.2 and 8.0. The release kinetic study showed that the release followed the classical first order pattern though the coated microcapsules used to be intact during the dissolution process, in case of the acidic pH media. The release kinetic was changed when the pH of the dissolution media was 7.2 and above. It was found that during the dissolution process the granules undergo erosion and the release mechanism does not follow a single process. PMID- 2329446 TI - Potential distribution across a plasma protein-coated poly(L-lactide) microcapsule surface. AB - A model is presented for the potential distribution across a protein-coated microcapsule membrane. The adsorbed protein layer is assumed to be divided into three sub-layers. The outer sub-layer is rich in positive fixed charges and the medium sub-layer in negative fixed charges, while the inner sub-layer may be either charged or uncharged. Also, the microcapsule membrane is negatively charged. The ionic partition coefficients into the inner sub-layer are less than unity, while those into the other sub-layers are unity. This model explains well the accelerated degradation of poly(L-lactide) microcapsules with an adsorbed protein layer onto their surface (Makino et al., 1987 c). PMID- 2329447 TI - Controlled release of nifedipine from gelatin microspheres and microcapsules: in vitro kinetics and pharmacokinetics in man. AB - Nifedipine was embedded in a gelatin matrix to develop a prolonged release dosage form. The effects of polymer/drug ratio, size of the beads, cross-linking with formaldehyde and ethylcellulose coating of the gelatin microspheres on the in vitro release rate of the drug were investigated. The data were analysed according to different laws that can govern the release mechanism: first-order, Higuchi square root of time, spherical matrix and zero-order. The in vitro release kinetics of nifedipine from gelatin microspheres were mainly first-order; from formaldehyde hardened gelatin microspheres, complied with the diffusion model for a spherical matrix, and from ethylcellulose-coated gelatin microspheres, obeyed zero-order kinetics. These findings suggest the possibility of modifying the formulation in order to obtain the desired controlled release of the drug for a convenient oral sustained delivery system. The pharmacokinetic parameters of nifedipine, after administration of a single oral dose of nifedipine-loaded hardened gelatin microspheres to volunteers, suggest that the preparation can be considered as a sustained release delivery system for nifedipine. PMID- 2329448 TI - Microencapsulation using poly(DL-lactic acid). I: Effect of preparative variables on the microcapsule characteristics and release kinetics. AB - Poly(DL-lactic acid) (DL-PLA, molecular weight 20,500) microcapsules containing phenobarbitone (PB) as a reference core were prepared using a water/oil (W/O) emulsion system. Surface morphology, particle size and 'encapsulation efficiency' of the microcapsules prepared using different preparative variables have been investigated. Buffer pH 9 was used as a dissolution medium to determine the affect of preparative variables on the release rate from these microcapsules. With an increase in temperature of evaporation the microcapsule surface became increasingly irregular and porous, due to deposition of phenobarbitone crystals near the vicinity of the microcapsule surface leading to rapid release of the core. The normalized release rate was found to increase exponentially with an increase in the temperature of evaporation. Microcapsule morphology was also severely affected due to differences in polymer concentration in the disperse phase solvent. With the increase in polymer concentration, the microcapsule surface was found to be increasingly irregular and non-continuous, due to rapid precipitation of the polymer. Increased polymer concentrations also increased mean microcapsule diameter. The release rate increased with the increase in polymer concentration due to surface defects and did not exhibit a straight line correlation. When core loading was very high (e.g. C:P, 2:1 and 1:1), crystals of phenobarbitone appeared at the surface and these caused a very rapid burst effect. However, microcapsules containing a lower phenobarbitone content were found to follow t1/2 dependent release. The encapsulation efficiency was not seriously affected due to variations in temperature of preparation and polymer concentration. However, with the decrease in initial core loading the encapsulation efficiency of microcapsules was found to be reduced. PMID- 2329449 TI - Microencapsulation using poly(DL-lactic acid). II: Effect of polymer molecular weight on the microcapsule properties. AB - Poly(DL-lactic acid) (DL-DPA) of three different molecular weights, 20,500; 13,300 and 5200, was used to prepare microcapsules containing differing contents of phenobarbitone (PB), as a reference core. A water/oil (W/O) emulsion evaporation method was used. The effect of polymer molecular weight on the particle size, 'encapsulation efficiency', morphology, density, thermal behaviour and swelling property has been reported. A general trend towards lowering the mean microcapsule size, both by volume and population, was observed with respect to lower polymer molecular weight. The gross morphology of the microsapsule surface, encapsulation efficiency and density were unaffected by variations in polymer molecular weight. Differential scanning calorimetric analysis of the microcapsules showed a lowering of glass transition temperature after microencapsulation. The melting endotherm for phenobarbitone also indicated the presence of crystalline drug in the microcapsule matrix. These microcapsules were found to swell in the aqueous environment and the mean size increased linearly with time. However, the rate of swelling was higher with low molecular weight polymer and also depended on core loading. PMID- 2329450 TI - The action of Triton X-100 and sodium dodecyl sulphate on lipid layers. Effect on monolayers and liposomes. AB - The action of two detergents, Triton X-100 and sodium dodecyl sulphate (SDS), on large, unilamellar liposomes was determined as liposome size variation, polydispersity and ability to release a soluble marker from liposomes. Triton X 100 produced stronger effects than SDS. Nevertheless, these differences in behaviour of such detergents could not be deduced from the interaction of the detergents with monolayers of the same composition as liposomes. PMID- 2329452 TI - Papers presented at the 36th annual congress of the British Association of Paediatric Surgeons. Nottingham, England, July 19-21, 1989. PMID- 2329451 TI - Preparation and in vitro evaluation of rosin microcapsules: solvent evaporation technique. AB - Free flowing, spherical rosin microcapsules were prepared by a method based on phase separation by solvent evaporation. Bentonite was used to prevent the agglomeration and coalescence of the dispersed polymer droplets. The effect of varying the core to coat ratio on micrometric and dissolution properties has been described. PMID- 2329453 TI - Advice to a resident: a surgeon's notebook. PMID- 2329454 TI - The relationship of class I MHC antigen expression to stage IV-S disease and survival in neuroblastoma. AB - Cultured human neuroblastoma cells express low levels of class I (MHC) surface antigen. In order to determine if this low expression is representative of the clinical tumor, this study investigates class I expression in archival human neuroblastoma. Whereas stages I to IV neuroblastoma expressed low levels of class I antigen, stage IV-S tumor cells expressed normal levels, similar to control tissues. Expression of class I antigen in tumors from survivors of stage III neuroblastoma was significantly greater than in tumors from nonsurvivors. Tumors comprised predominantly of ganglion cells expressed significantly more class I antigen than neuroblasts. These data suggest that class I MHC expression may play a role in the natural history of human neuroblastoma. PMID- 2329455 TI - Problems of mass screening for neuroblastoma: analysis of false-negative cases. AB - The Japanese mass screening (MS) system for neuroblastoma at 6 months of age has resulted in the earlier diagnosis of the tumor with excellent therapeutic results. However, some problems are involved in the present MS system. We present six false-negative cases, ages ranging from 1 year 11 months to 3 years 11 months. Neuroblastoma cell taken from four of these patients were studied biologically. These patients had advanced disease (one was stage III; five were stage IV). Three of the patients have died and one is terminally ill despite undergoing surgery combined with intensive chemotherapy. Cytogenetic analysis performed in three cases showed that all the cases had diploid chromosome mode associated with 1P-, double minutes (DMs), or marker chromosomes. N-myc oncogene analysis, performed in four cases, showed amplification in two; one patient had diploid chromosomes, but the other was not examined cytogenetically. These findings were strikingly different biologically from those of cases found by MS. The majority of neuroblastomas detected by MS were found to be triploid tumors without N-myc amplification. These findings suggest that the main reason for the false-negative results in the patients we examined is that they were tumor-free or the tumors were so small in size that they were unable to produce urinary vanillylmandelic acid and or homovanillic acid levels high enough to be detected at the time of MS. Therefore, we conclude that MS at 6 months of age is too early to detect neuroblastoma with a diploid chromosome mode and/or amplified N-myc oncogene. We propose that MS at the age of 1 year 6 months would be more effective to pick up these cases, because treatment strategies depend on the different biological characteristics of tumor cells. PMID- 2329456 TI - Allogeneic transplantation of fetal rat intestine: anastomosis to the normal bowel of the host. AB - We have examined the functional integrity of the transplanted fetal rat intestine following anastomosis of the transplant to the intestine of the host after successful allogeneic transplantation of fetal rat intestine into the peritoneal cavity of the host. In the syngeneic group all the 10 animals survived after end to-side anastomosis. After end-to-end anastomosis 11 of 20 rats survived in the syngeneic group. In the allogeneic group we saw a marked host versus graft reaction (HVGR) after end-to-end anastomosis when treated orally with cyclosporin A in a dosage of 10 mg/kg per day. After administering the cyclosporin A parenterally, the survival rate in the allogeneic group after end-to-end anastomosis was 45%. PMID- 2329457 TI - Hyponatraemia and intracellular water in sepsis: an experimental comparison of the effect of fluid replacement with either 0.9% saline or 5% dextrose. AB - Hyponatraemia associated with sepsis is known to have an increased morbidity and mortality. The cause of this phenomenon is unknown, but may be related to dilution of the extracellular space with retained exogenous fluid. Fluid and ion redistribution across the cell membrane of striated muscle was investigated in an animal sepsis model and compared with sham controls. The objective was to study the effect of different volumes of fluid replacement with either 0.9% saline or 5% dextrose. Significant shifts of sodium, chloride, and water occurred into the cell in all septic animals but not in controls. This trend was exacerbated by the use of dextrose for intravenous replacement even when the estimated normal fluid requirements had not been exceeded. Hyponatraemia and plasma hypoosmolality were induced only in septic animals, which received 100% of their fluid requirements as dextrose. These animals at the same time had significantly reduced extracellular and increased intracellular volumes compared with controls and the septic animals that received saline replacement. It is concluded that the hyponatraemia and plasma hypoosmolality that occurs in these animals is caused by a combination of intracellular shift of sodium and water, and dilution of the extracellular space, probably on the basis of physiological antidiuretic hormone (ADH) secretion. Dextrose (and by implication 4% dextrose/0.18% saline) is inappropriate, potentially dangerous, and should be avoided in these circumstances. PMID- 2329458 TI - Experimentally induced congenital diaphragmatic hernia in rats. AB - Experiments to induce congenital diaphragmatic hernia (CDH) in rats, by means of administering a single dose of 2,4-dichlorophenyl-P-nitrophenyl (Nitrofen) on the 10th day of gestation, are reported here. Previously, congenital diaphragmatic hernia has been induced in sheep late in fetal development, and in mice early in gestation. The rat model, including a control group, was used to evaluate lung development and the presence of lung hypoplasia by morphometrical analysis. It was found that the single dose of Nitrofen, given 5 days before the normal closure of the diaphragm in the rat, leads to a high incidence of diaphragmatic hernia, mainly on the right side, and highly abnormal lung development (hypoplasia) comparable to the human situation. Both the lung weight/body weight index as well as the radial alveolar count were significantly lower in animals with CDH (P less than .05). This animal model offers a good opportunity to study abnormal lung development in relation to ventilatory capacity and pulmonary vascular reactivity. PMID- 2329459 TI - Studies in fetal wound healing, VII. Fetal wound healing may be modulated by hyaluronic acid stimulating activity in amniotic fluid. AB - Fetal wound healing occurs rapidly and without inflammation, fibrosis, or scar formation. It is a process fundamentally different from adult wound healing. The mechanisms that underlie such unique healing properties are unknown. However, hyaluronic acid, a glycosaminoglycan component of the extracellular matrix, is prominent throughout the course of fetal wound healing, and is thought to play a major role in the healing process. Amniotic fluid contains high levels of hyaluronic acid. Amniotic fluid also contains a number of potent growth factors that are critical for fetal development. In this report, a new factor in amniotic fluid that stimulates deposition of hyaluronic acid is described. This activity is measured in an in vitro assay system in which cultured fibrosarcoma cells are used as indicator cells. Amniotic fluid thus provides two separate mechanisms for the deposition of hyaluronic acid. One is by exogenous application directly onto fetal skin wounds; the second is by providing a factor to increase the production of hyaluronic acid endogenously, by stimulating cells around the wound site. The resulting hyaluronic acid-rich area may support the ability of the fetal wound to heal with its unique properties. PMID- 2329460 TI - The role of the paediatric surgeon in alleged child sexual abuse. AB - Two hundred ninety cases of alleged child sexual abuse (CSA) were reported in Edinburgh and the Lothian region over the 7-year period from 1982 through 1988. We have found an increase in the incidence of alleged CSA, which has resulted in greater involvement of the paediatric surgeon. CSA was found to be occurring with increasing frequency in younger children. The physical examination and the role of general anaesthesia are discussed together with the data about the collection of forensic material. PMID- 2329461 TI - Ethical dilemmas of health care in the developing nations. AB - Limited resources, widespread poverty, and the absence of health insurance pose daily ethical problems for Third World physicians, who must balance their roles as individual patient advocates against a desire to provide health care to the greatest number of children. Pakistan has a per capita income of Rs. 7,220 (US$ 380) per year, or Rs. 800 (US$ 32) per month. The annual population growth of the country is 3.1%, and approximately 360,000 infants are born each year in Karachi, the largest city in the country. The Aga Khan University Hospital, a private teaching institution, is the only hospital in Karachi with a Level III Neonatal Intensive Care Unit (NICU). The financial and medical data of 200 infants admitted to the NICU in 1988 were reviewed retrospectively, and compared with those of two specific subgroups. (1) Among 15 infants who underwent surgical intervention, the average total cost of hospitalization was Rs. 36,040 (US$ 1,900) per patient, with an average daily cost of Rs. 923 (US$ 49). The longest hospital stay was 6 months, for a child who had total colonic aganglionosis associated with a short gut syndrome. There were two deaths in this group. (2) Of the 21 premature neonates admitted having Idiopathic Respiratory Distress Syndrome (IRDS) during this period, the total hospitalization cost per patient was Rs. 23,260 (US$ 788), with a daily cost of Rs. 1,050 (US$ 55). Eleven patients required ventilatory support. There were 16 survivors. Among both groups, 6% of all revenues generated in the NICU were used to help families pay for the bills under a welfare scheme. PMID- 2329462 TI - Long-term follow-up after surgery for patients with biliary atresia. AB - Long-term results after surgery for biliary atresia (BA) in 48 patients, ranging in age from 10 to 33 years, were examined. There were 19 males and 29 females. Twelve had correctable type BA and 36 had the noncorrectable type. Forty-one cases had no jaundice; seven did. Thirty-seven of the 48 cases were leading normal lives. Among them, six cases were enjoying their lives after overcoming sequelae, such as portal hypertension. The main morbidities of the remaining 11 long-term survivors were jaundice and portal hypertension. The growth of most cases were comparable to those of the normal Japanese population. The data of liver function tests were variable and disclosed a moderate degree of abnormality in patients mainly complicated by cholangitis. Eleven cases, including six jaundice cases, required treatment for esophageal varices and/or hypersplenism. In conclusion, the cured states of most cases without jaundice are satisfactory and these former patients have achieved a favorable quality of life. Early operations are essential to obtain good short-term results as well as good long term results. PMID- 2329463 TI - Cervical Barrett's esophagus: a common complication of gastric tube reconstruction. AB - Upper gastrointestinal endoscopy was performed on 14 of our 18 long-term (more than 2 years) gastric tube esophagus survivors, with special attention paid to cervical gastric metaplasia. Barrett's esophagus was found in 10 patients. In eight cases, this could also be histologically verified. Three patients had esophagitis, but no verified gastric metaplasia. Isotope reflux studies were performed on six patients, all having both endoscopically and histologically shown pathology in the cervical esophagus. Reflux was provoked by putting patients in different positions. Only one patient showed gastrotubal reflux, and only in the prone Trendelenburg position. We conclude that Barrett's esophagus is a common complication of gastric tube patients, and is probably due to acid secreted by the tube itself. Life-long endoscopic follow-up of these patients is warranted. PMID- 2329464 TI - New insights into the pathogenesis of appendicitis based on immunocytochemical analysis of early immune response. AB - Although appendicitis is the most common condition requiring emergency surgery, the pathogenesis of this disease is poorly understood. In this study, local immune responses in acute appendicitis were investigated, using an experimental rabbit model, as well as in different grades of appendicitis in humans. Polymorphonuclear leukocyte (PMN) and plasma cell isotypes infiltration was measured in 24 New Zealand-bred white rabbits following experimental obstruction of the appendiceal lumen for periods ranging from 30 minutes to 24 hours. Significant infiltration of PMNs, IgM, and IgG plasma cells was noted at 30 minutes following obstruction, and IgA plasma cells were noted at 2 hours after obstruction. The immunopathological features observed in the study of human appendicitis clearly demonstrated the role of plasma cell infiltration in the immunopathogenesis of appendicitis. IgA and IgG plasma cells were significantly increased in the lamina propria of both focal and acute suppurative appendicitis, compared with controls (P less than .001). In focal appendicitis, in which the focus of inflammation is confined to only a few serial sections, the increased IgA and IgG plasma cell infiltration was present throughout the entire length of the resected organ. The possibility, as seen in this study, that antigen stimulation of the effector immune system could give rise to appendicitis, provides new insights into the diversity of inflammatory responses contributing to diseases of the intestinal tract. This previously unrecognised concept in the pathogenesis of appendicitis requires further elucidation of the stimulating agent, and in particular the T-cell recognition process. PMID- 2329465 TI - Pseudomembranous enterocolitis--a potentially lethal disease. AB - The cases of nine children with pseudomembranous enterocolitis, five of whom died, are reported here. Six had prior antibiotic therapy, and in eight there were other diseases present that were considered to contribute to the development of this disease. Awareness of this condition, which requires aggressive medical and surgical management, is discussed. PMID- 2329466 TI - Origin, course, and endings of abnormal enteric nerve fibres in Hirschsprung's disease defined by whole-mount immunohistochemistry. AB - Accurate delineation of the intramural pathway of abnormal enteric nerve fibres in Hirschsprung's disease has previously proved impossible because the neural network is invariably transected in conventional histological sections. With the technique of wholemount immunohistochemistry (WI), the bowel segment is converted into a rectangular sheet and the serosa, long muscle (LM), circular muscle (CM), submucosa, and mucosa are separated into layers to allow each nerve plexus to be examined intact and neural pathways traced. The entire resected bowel specimens of nine HD infants and five infants serving as controls were investigated, using neuron-specific enolase and vasoactive intestinal peptide (VIP) for WI. The major new findings are (1) More VIP fibres were observed in aganglionic bowel with WI than with conventional sections; (2) Thick nerve trunks in aganglionic bowel do not descend from intrinsic neurons of oligoganglionic bowel as previously suggested, but have an extrinsic origin, accompanying blood vessels as small nerves initially, expanding subsequently, and ending blindly in submucosa; (3) CM nerve fibres follow muscle fibres concentrically for long distances in aganglionic bowel; and (4) LM nerve fibres meander in spirals in aganglionic bowel instead of running straight. This study shows that (1) WI is highly sensitive; (2) nerve fibres in aganglionic bowel have an extrinsic origin; and (3) innervation abnormalities in Hirschsprung's disease are not only quantitative but qualitative. PMID- 2329467 TI - The influence of pH on rectal absorption of sodium benzoate studied in man by rectal lumen perfusion. AB - The influence of pH on rectal absorption of sodium benzoate in man was studied by means of a rectal lumen perfusion method and compared with in vitro measurements on diffusional transport of sodium benzoate across an octanol/water interface. For nonbuffered solutions of benzoate in vitro, it was shown that mass flux across an octanol/water interface occurs in agreement with the pH-partition model. In vivo however, mass flux increases less with decreasing pH of unbuffered perfusate than is anticipated on the basis of the pH-partition model. Probably an alkaline flow across the rectal mucosa into the lumen is present as a physiological neutralization mechanism. In contrast, buffered solutions of benzoate show a linear relationship between mass flux and decreasing pH in vitro as well as in vivo. The effect of buffer on the concentration profile of benzoic acid is qualitatively explained. It is shown that an alkaline flow across the rectal mucosa only slightly influences absorption of benzoic acid from strongly buffered solutions in the rectal lumen. It is concluded that the use of strong buffers in rectal solutions induces a drastic effect on the pH of the boundary layer, an effect not seen for unbuffered solutions. This phenomenon does not invalidate the pH-partition hypothesis but can be explained by it. PMID- 2329468 TI - Saturable rate of cefatrizine absorption after oral administration to humans. AB - This study examined the absorption kinetics of cefatrizine, an amino-beta-lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier mediated transport previously reported to occur in the gastrointestinal tract of rats. PMID- 2329469 TI - An experimental model for pharmacokinetic analysis in renal failure. AB - A renal failure model was developed in the dog to evaluate the effect of varying degrees of renal failure on drug pharmacokinetics. A controlled impairment of renal function was induced by electrocoagulating portions of one kidney and excising the contralateral kidney. The magnitude of renal dysfunction, defined by the percentage of normal glomerular filtration rate (% NGFR), was estimated by 125I-iothalamate total body clearance. The model was evaluated by comparing the pharmacokinetics of oxytetracycline (OTC) before and after the induction of renal failure in two experiments: single intravenous dose (11 dogs); single intravenous and oral doses (8 dogs). Renal failure (RF) was studied in three classes according to % NGFR: less than 25%, severe RF; 25-39%, moderate RF; and greater than or equal to 40%, mild RF. Significant reductions were observed over RF class in OTC pharmacokinetic parameters for elimination and distribution but not for oral absorption. PMID- 2329470 TI - Advances in cataract and intraocular lens surgery. PMID- 2329471 TI - Posterior polar cataracts: a predisposition to intraoperative posterior capsular rupture. AB - We performed phacoemulsification or planned extracapsular cataract extraction on posterior polar cataracts in 31 eyes of 22 patients and experienced eight cases of posterior capsular rupture (26%). Capsular rupture occurred during removal of the posterior polar opacity or during cleaning of the posterior capsule after the opacity had been removed. We believe that excessive adherence of the opacity to the posterior capsule and unusual thinness of the capsule predisposed these eyes to posterior capsular rupture. PMID- 2329472 TI - Natural history of cystoid macular edema in pseudophakic bullous keratopathy. AB - A retrospective review of 25 consecutive patients having penetrating keratoplasty (PKP) with the preoperative diagnoses of pseudophakic bullous keratopathy (PBK) and cystoid macular edema (CME) was undertaken to analyze the natural history of preoperative CME following keratoplasty. Follow-up ranged from 13 to 54 months with a mean of 27 months. All patients had intraocular lens exchanges with 24 receiving posterior chamber lenses; 23 had lenses sutured to the posterior iris. Sixteen patients (64%) recovered a visual acuity of 20/40 or better. The average time for visual recovery to 20/40 was nine months with a range of two to 45 months. Eighteen (72%) had resolution of angiographic CME. Three patients previously diagnosed as having chronic CME recovered visual acuity of 20/40 or better. Cases of PBK with CME may have an excellent visual prognosis if the IOL is managed properly at the time of PKP. PMID- 2329473 TI - Improved biocompatibility of intraocular lenses by heparin surface modification: a 12-month implantation study in monkeys. AB - To evaluate the long-term biocompatibility and potential side effects of heparin surface modification of a poly(methyl methacrylate) intraocular lens (IOL), a heparin surface modified IOL was implanted in the left posterior chamber of 24 cynomolgus monkeys and a reference IOL (without surface modification) was implanted in the right eye in 12 of these animals. Twelve eyes were not operated on. Eleven eyes in seven monkeys were lens extracted as a control of the surgical method. Slitlamp examinations and intraocular pressure recordings were made one day, one and two weeks, and 1, 2, 2 1/2, 3 1/2, 6, 8, 10, and 12 months after the operation. Eleven monkeys were sacrificed after 3 1/2 months and the remaining animals after 12 months for morphological examination of the eyes. Slitlamp and morphological examinations showed that cell deposits, pigmentation, and posterior synechias were significantly less in eyes with heparin surface modified IOLs than in eyes with reference IOLs throughout the 12-month observation period. The intraocular pressure was equally reduced in eyes with heparin surface modified IOLs and reference IOLs for about one month, after which it returned to normal. No side effects following the implantation of heparin surface modified IOLs were observed. We concluded that heparin surface modification of IOLs is efficient for long-term reduction of cell deposits and posterior synechias after implantation in monkey eyes and may also be effective in lowering the degree of side effects to IOL implantation in humans. PMID- 2329474 TI - Optical design of poly(methyl methacrylate) intraocular lenses. AB - The effect of poly(methyl methacrylate) intraocular lens shape on optical performance of pseudophakic eyes was investigated. Image quality criteria included wave aberrations, spot diagrams, longitudinal aberrations, the modulation transfer function, and an optimization procedure. For eyes with corneal asphericities encompassing most of the population, the optimum lens form for on-axis vision is close to plano-convex, with the more curved surface facing the cornea. This applies whether lenses are correctly centered, tilted, or decentered. For small off-axis angles, optimum lens shape varies with the ocular parameters. Good intraocular lens shapes range from the plano-convex to the equi convex. Plano-convex lenses with the curved surface facing the retina are not recommended. PMID- 2329475 TI - Effect of intraocular lens optic design on posterior capsular opacification. AB - Secondary capsular opacification is a common complication of extracapsular cataract extraction. We have done a retrospective study of 1,040 consecutive posterior chamber implants using four optic designs. The annual incidence of capsular opacification requiring capsulotomy was calculated to see if the optic design was a possible factor. The laser ridge and laser "peg" optics each had a cumulative capsulotomy rate of over 40.0% at three years and the convex-plano optic, over 40.0% at five years. Optics of plano-convex/biconvex designs had a cumulative capsulotomy rate of 5.0% at three years and 6.5% at five years. These results strongly suggest that capsular opacification is retarded when there is broad adhesion of the lens optic to the posterior capsule. PMID- 2329476 TI - Indications for the multizone bifocal implant. AB - A significant improvement in unaided visual standards may be achieved by switching from a monofocal to a 3M diffractive bifocal implant; however, this results in a loss of clarity, particularly for small print, in some patients. In a prospective study of 55 bifocal eyes and 55 monofocal eyes, best-case analysis showed 81% of 52 eyes with bifocal implants could read J5 with their distance correction compared with 21% of the control eyes and 56% could read J2 with the distance correction compared with 2% of the control eyes; 75% of bifocal eyes could read both 20/40 and J3 without any aid compared with 33% of the control eyes. The 3.5 diopter focus difference in the bifocal lens produced commendable results, with 52% requiring no spectacle reading addition. However, the fact that 17% of bifocal eyes could not read J2 highlights certain drawbacks that are relevant to indications for use. PMID- 2329477 TI - Role of the posterior capsule in the aqueous-vitreous barrier in aphakic and pseudophakic eyes. AB - Clinical observations have shown that an intact posterior capsule between aqueous and vitreous may function as a barrier to low and high molecular weight substances, e.g., prostaglandins or the angiogenic factor. To determine if this protective barrier breaks down after posterior capsulotomy, we examined the distribution of fluorescein in human eyes after intracapsular cataract extraction (ICCE), extracapsular cataract extraction (ECCE) and intraocular lens (IOL) implantation with capsulotomy, and ECCE and IOL implantation without capsulotomy in 12 patients each. After ICCE and after ECCE and IOL implantation with capsulotomy, diffusion of fluorescein into the vitreous showed similar values. These values were significantly higher than those obtained in patients after ECCE or ECCE and IOL implantation without capsulotomy. This leads us to believe that an intact posterior capsule prevents the diffusion of soluble substances. PMID- 2329478 TI - Biometry of the posterior lens capsule: a new method to predict pseudophakic anterior chamber depth. AB - The distance between the anterior corneal vertex and the posterior lens capsule was measured in 60 eyes before and three months after extracapsular cataract extraction with implantation of a posterior chamber lens. The preoperative capsule position ranged from 6.15 mm to 8.60 mm and averaged 7.64 +/- 0.47 mm (+/ SD). All posterior lens capsules had moved anteriorly following surgery. The postoperative capsule position ranged from 4.31 mm to 5.53 mm and averaged 4.93 +/- 0.29 mm. The postoperative capsule position could be predicted by the following optimized multiple linear regression equation: 2.4 + 0.011 x patient age + 0.171 x anterior chamber depth + 0.051 x axial length. The multiple correlation coefficient was 0.48. The postoperative anterior depth could be predicted with a correlation coefficient of 0.61 by subtracting both the averaged value of the clinical "laser space" and the exact central implant thickness from the estimated position of the posterior lens capsule. We suggest that this principle for predicting the postoperative anterior chamber depth may be useful for a number of lenses with different designs. PMID- 2329479 TI - Study of the lens epithelial cell density in cataractous eyes operated on with extracapsular and intercapsular techniques. AB - Epithelial cell counting was performed in 47 fragments from lens anterior capsules obtained during extracapsular and intercapsular surgery. Mean cell count was 3,277 cell/mm2; there was no correlation between cell number and age and no significant difference in cell counts between extracapsular and intercapsular surgery. There were, however, significant differences between advanced cataracts and the other cataract types (2,947 vs. 3,356). This may be important in explaining the differences in regenerative opacification of the posterior capsule in the different types of cataracts. PMID- 2329480 TI - Optical resolution of foldable intraocular lenses. AB - Recently manufactured intraocular lenses (IOLs) (STAAR AA 4203 made of silicone and IOGEL PC-12 made of polyHEMA) were tested before and after implantation simulation for axial optical resolution (model eye), for optical surface quality (photokeratoscope), and for surface microtrauma (scanning electron microscopy). At a 3 mm pupillary opening, both lens types achieved a mean axial resolution of 1.25 (range 1.0 to 1.5) on an optotype analogous resolution target. When the pupillary opening was increased to 6 mm, polymacon IOLs showed only a moderate resolution decrease (up to one line) and loss of contrast (up to 30%); silicone IOLs showed almost no decrease. Photokeratoscopic evaluation revealed that a circular optical nonhomogeneity at the peripheral optical zone of the hydrogel IOLs is the source of this impairment. Groove-like surface deformities occasionally observed by scanning electron microscopy did not detectably decrease resolution or contrast. PMID- 2329481 TI - Theoretical versus SRK I and SRK II calculation of intraocular lens power. AB - The predictability of a theoretical, computerized (PC-assisted) intraocular lens (IOL) power calculation method and of the Sanders-Retzlaff-Kraff [SRK] I and II methods was evaluated from preoperative and postoperative biometry in 202 cataractous patients who had extracapsular cataract extraction (ECCE). The theoretical method resulted in the lowest range and standard deviation of the error, and the highest correlation coefficient between the observed and the predicted refraction (P less than .05). The superiority of the theoretical approach was most clearly demonstrated when the postoperative measurements were used in the predictions (P less than .001). This demonstrated the potential accuracy of the formula used and the importance of incorporating methods to predict the IOL position after surgery. If the prediction of the IOL chamber depth was properly corrected for the axial length dependence, a high prediction accuracy could be obtained in short as well as in long eyes. PMID- 2329482 TI - Evaluation of flurbiprofen-exposed irises to acetylcholine anterior chamber irrigation. AB - Flurbiprofen (Ocufen), an antiprostaglandin, has been introduced into cataract surgery. It is used to prevent intraoperative miosis by blocking inflammatory mediator formation. Ocufen has been noted to diminish the controlled miosis produced by using acetylcholine in the operative period. This study evaluated the pupillary response to acetylcholine after it had been exposed to Ocufen. This was done using a control versus a study eye in 16 rabbits dilated with phenylephrine hydrochloride and cyclopentolate hydrochloride. The pupil diameters were measured at baseline, then the rabbits' anterior chambers were irrigated with an acetylcholine solution. The resultant pupillary diameters were measured at one and five minutes. At five minutes post-irrigation there was a statistically significant greater constriction in the control group than in the Ocufen group. This implies that Ocufen dampens the iris musculature's response to acetylcholine. PMID- 2329483 TI - Modified triple procedure using a temporary keratoprosthesis for closed-system, small-incision cataract surgery. AB - In patients with corneal disease and cataract, the combined surgical approach yields quick rehabilitation and excellent visual results. Working on an open eye for cataract removal and posterior chamber lens implantation, however, makes the procedure risky and difficult. Using a temporary keratoprosthesis and a small incision technique, surgery can be performed in a fully closed system, optimizing the safety and precision of the procedure. PMID- 2329484 TI - Comparison of A-scan device accuracy. AB - A-scan biometry is recognized as a useful aid in predicting intraocular lens power. Measurements are reported to be accurate to better than +/- 0.1 mm. Three biometry devices were compared in examinations of 159 persons, each examination being repeated several times. Axial length averaged 23.77 mm when measured by the immersion technique; applanation and modified applanation techniques yielded 0.1 mm and 0.3 mm shorter distances, respectively. Measured values of axial lengths did not have the same probability of being measured, even if they were close together. Results were not distributed in smooth Gaussian curves; on the contrary, clusters of values, on the pattern of our choice of ultrasound wavelength, were seen even when biometry was performed with electronic gates in the devices. Retest reliability decreased when short distances in the anterior segment of the eye were measured. Measurements of lens thickness were less readily reproducible in cataractous lenses than in healthy young eyes; anterior chamber depth, on the other hand, was measured more reliably in cataract patients. This last finding may have resulted in part from uncertainties about ultrasound velocity in the cataractous lens and in part from accommodation. In cataract patients, axial length was measured most reproducibly by the immersion technique; it was measured less accurately in young healthy eyes with a modified applanation device. PMID- 2329485 TI - Two-stage capsulorhexis for endocapsular phacoemulsification. AB - The continuous tear anterior capsulotomy or capsulorhexis technique is important for safe, successful cataract extraction and intraocular lens (IOL) implantation surgery. A two-stage continuous tear capsulotomy or capsulorhexis extends the possibility of achieving continuous tear capsulotomy to challenging and complicated cases. In endocapsular phacoemulsification this technique preserves the integrity of the capsule because it prevents the extension of radial tears in the capsule and thus facilitates safe cataract extraction and secure in-the-bag IOL placement. The benefits and advantages of the continuous tear capsulotomy are preserved by two-stage capsulorhexis. PMID- 2329486 TI - Extracapsular cataract extraction with keyhole capsulorhexis and lens epithelial cell removal. AB - Circular capsulorhexis with its round continuous anterior capsule opening allows secure fixation of a posterior chamber intraocular lens. The smooth capsular margin edge reduces stress concentration and the risk of radial tears but it makes nucleus delivery in planned extracapsular cataract extraction very difficult. This report describes a technique of small circular capsulorhexis with one relaxing incision that gives a keyhole-shaped capsular opening. A new irrigating capsule retractor for nucleus hydrodissection is also described. This technique is safe and highly reproducible and it allows secure posterior chamber lens fixation. PMID- 2329487 TI - Endocapsular closed chamber technique for disc lens implantation. AB - A simple endocapsular technique for implantation of an 8 mm disc lens is described. Its main features are a scleral three-plane incision, a vertical-stab capsulotomy, cortical hydrodissection, a closed chamber technique during placement of the intraocular lens in the capsular bag, implantation under air and fluid, wherever feasible, and optional anterior capsulectomy with a 27-gauge needle bent at the tip. This technique requires no complicated equipment and allows atraumatic implantation of the disc lens with maximum control of anterior chamber depth. PMID- 2329488 TI - One-movement insertion of the superior loop into the bag. AB - An efficient, simple technique for one-movement insertion of the superior intraocular lens loop into the capsular bag is described. This bimanual technique avoids undue stress on the capsular bag and zonules, may be used with all extracapsular techniques, and is suitable for almost all flexible loop intraocular lenses designed for in-the-bag implantation. PMID- 2329489 TI - New spatula to facilitate bimanual phacoemulsification. AB - In recent years bimanual phacoemulsification has become an increasingly popular method of cataract extraction. We describe a new spatula designed to manipulate and protect the posterior capsule safely during phacoemulsification. In addition, this spatula can be used to facilitate irrigation/aspiration. PMID- 2329490 TI - Consultation section. Surgical correction of aphakia with intraocular lens implantation. PMID- 2329491 TI - Refraction factor. PMID- 2329492 TI - Open loop soft intraocular lens. PMID- 2329493 TI - Early capsular fibrosis with posterior convex surface posterior chamber intraocular lenses. PMID- 2329494 TI - Anesthetic agents used in cataract surgery. PMID- 2329495 TI - The "Thornton ring plus" for keratotomies. PMID- 2329496 TI - Anterior segment pressure gradient. PMID- 2329497 TI - On the mechanism of the different sensitivity of Purkinje and myocardial fibers to strophanthidin. AB - The mechanism of the different sensitivity of Purkinje and myocardial fibers to strophanthidin was studied in these tissues isolated from the same hearts. Membrane potentials, force and, in some experiments, intracellular sodium activity were recorded under conditions that vary the sodium load in the absence and presence of strophanthidin. Strophanthidin (0.1-0.3 microM) increased force in percent terms more and at a faster rate in Purkinje than in myocardial fibers. Tetrodotoxin (TTX, 2 microM) markedly reduced whereas high [Na]o (176.6 mM) and veratridine (0.2 microM) potentiated strophanthidin inotropy in Purkinje but not in myocardial fibers. The rate of force development was augmented by high [Na]o and veratridine in Purkinje fibers but in myocardial fibers this effect was absent with high [Na]o and smaller with veratridine. Strophanthidin increased the action potential duration at plateau level in Purkinje and decreased it in myocardial fibers. The effects of TTX, high [Na]o and veratridine on the action potential were more pronounced in Purkinje than in myocardial fibers. TTX decreased far more and adding strophanthidin increased intracellular sodium activity (aiNa) less in Purkinje fibers. Strophanthidin increased aiNa to a similar extent in the presence of high [Na]o and veratridine in the two tissues. Thus, changes in Na influx modify the action potential duration, force and strophanthidin inotropy more in Purkinje than in myocardial fibers. This greater sensitivity of Purkinje fibers to strophanthidin does not appear to be related to a larger increase in aiNa, but rather to the changes in action potential (and consequent changes in calcium influx). PMID- 2329498 TI - Effects of repeated fenfluramine administration on indices of monoamine function in rat brain: pharmacokinetic, dose response, regional specificity and time course data. AB - The pharmacokinetics and neurochemical effects of repeated fenfluramine administration in rats (1-24 mg/kg s.c., b.i.d. for 4 days) were examined with respect to dose dependence, regional specificity and time course of recovery. Fenfluramine administration resulted in parallel increases in plasma and brain concentrations of the drug and its metabolite, norfenfluramine, which were dose related but nonlinear. Doses of 1 and 2 mg/kg fenfluramine increased brain serotonin (5-HT) and 5-hydroxyindoleacetic acid with no significant effects on 5 HT uptake sites. Higher doses of fenfluramine (4-24 mg/kg) reduced all three brain 5-HT markers with maximal decreases (80%-90%) occurring at 12 mg/kg. High dose (24 mg/kg) fenfluramine administration led to larger decreases in 5-HT markers in neocortex, striatum and hippocampus than in hypothalamus, brain stem and spinal cord. Following 80% to 90% reductions of the 5-HT markers in neocortex and hippocampus at 18 hr after drug treatment, 5-HT and 5-hydroxyindoleacetic acid returned to control levels by 4 and 16 weeks, respectively, but 5-HT uptake sites initially recovered more slowly, with a 25% reduction still evident at 8 months. At this time 5-HT and 5-hydroxyindoleacetic acid were again reduced. Fenfluramine administration produced dose-dependent and biphasic effects on brain dopamine markers. Increases in homovanillic acid levels were apparent at 2 hr, whereas decreases in the levels of dopamine, homovanillic acid and dihydroxyphenylacetic acid were evident at 18 hr post-treatment. Norepinephrine levels were only decreased by doses of fenfluramine greater than or equal to 4 mg/kg. Fenfluramine administration did not cause long-term alterations in dopamine or norepinephrine uptake sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329499 TI - The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary ammonium derivatives with subtypes of muscarinic receptors in brain and heart. AB - The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary derivatives with muscarinic receptors was investigated in the brain and heart. The potency of the tricyclic derivatives for inhibiting the binding of 11[[2-[(diethylamino) methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b] [1,4] benzodiazepine-6-one to M2 muscarinic receptors in cerebral cortex was similar to that measured in competitive binding experiments with the nonselective muscarinic antagonist [3H]N-methylscopolamine in the corpus striatum and heart. Moreover, the tricyclic derivatives antagonized muscarinic receptor-mediated inhibition of adenylate cyclase activity with similar potency in the corpus striatum and heart, and there was good agreement between the affinities of the tricyclic derivatives when measured by radioligand binding and by antagonism of the adenylate cyclase response. Our results show that amitriptyline, doxepin and imipramine lack selectivity for subtypes of the muscarinic receptor. PMID- 2329500 TI - Effects of dose, age, inhibition of metabolism and elimination on the toxicokinetics of 2-butoxyethanol and its metabolites. AB - Acute exposure to 2-butoxyethanol (BE) causes dose- and age-dependent hemolytic anemia in rats. Recently, we have shown that butoxyacetic acid (BAA) is the proximate hemolytic agent and that inhibition of alcohol or aldehyde dehydrogenases protected rats against BE-induced hemolytic anemia. In the present investigations, the kinetics of 14C-BE metabolism and clearance were studied in control adult (3-4 months old) and old (12-13 months old) male F344 rats and in adult male F344 rats treated with pyrazole, cyanamide or probenecid. Our results showed that the area under the curve (AUC), maximum plasma concentration (Cmax) and systemic clearance (Cls) of BE were dose-dependent. In contrast, there was no effect of dose on half-life (T1/2) or volume of distribution (Vd) of BE. These results also showed that there was no age effect on T1/2, Vd or Cls of BE. However, Cmax and AUC of BE increased as a function of age. Also, analysis of variance indicated no significant interactions (P less than or equal to .05) between dose and age in relation to BE kinetics. As expected, inhibition of BE metabolism by pretreatment of rats with pyrazole or cyanamide resulted in a significant increase in the T1/2 and AUC of BE, whereas it caused a significant decrease in the Cls. Furthermore, pyrazole had no effect, whereas cyanamide had decreased Vd of BE. Analysis of the toxicokinetic parameters of BAA revealed that T1/2, AUC and Cmax of BAA were directly related to the age of the rats and the dose of BE administered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329501 TI - Opioid regulation of mucosal ion transport in the mouse isolated jejunum. AB - Opioid control of mucosal ion transport was examined in intact, full thickness preparations of mouse jejunum in vitro, using standard Ussing chamber techniques. DPDPE and DAMGO were used as selective agonists for delta and mu subtypes of opioid receptors, respectively, whereas U50,488H [trans-(+-)-3,4-dichloro-N-Me-N [2-(1-pyrrolidinyl]-benzene-acedamid+ ++ e- methanesulfonate] and U69,593 [(5 alpha, 7 alpha, 8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidiny)-1- oxa-spiro-(4,5)-dec 8-yl]-benzeaneacetamide] were used as selective agonists at the kappa-opioid receptor. When added to the serosal medium of intact tissues, DPDPE, DAMGO, U50,488H and morphine, but not U69,593, produced a concentration-dependent reduction of basal transmural potential difference and short-circuit current (Isc), and an increase in tissue conductance. DPDPE was 41-, 341- and 476-fold more potent than DAMGO, U50,488H and morphine, respectively, in producing these effects, although all these compounds were equiefficacious. DPDPE, but not DAMGO, U50,488H or U69,593, caused a similar effect on basal Isc when added to the mucosal medium. Naloxone produced a rightward shift in the concentration-effect curve for DAMGO and DPDPE, yielding distinct Ke values for naloxone of 9.7 +/- 0.5 and 42.9 +/- 7.9 nM, respectively. In contrast, ICI 174,864, a delta selective antagonist, blocked the Isc response induced by DPDPE but not DAMGO. The Isc response of U50,488H, however, was neither blocked nor reversed by naloxone or ICI 174,864, nor blocked by norbinaltorphimine, suggesting that the response was not mediated via opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329502 TI - Age-dependent baroreflex attenuation by centrally infused verapamil in rats. AB - Because oral administration of verapamil for 6 days reduces reflex tachycardia without affecting reflex bradycardia, we tested chronotropic baroreflexes in conscious rats aged 5 or 15 months before and after verapamil was infused intracerebroventricularly for 6 days to determine whether a central action contributes to the reflex attenuation. Baroreflex responses consisted of reflex bradycardia elicited during pressor responses to methoxamine and reflex tachycardia during depressor responses to sodium nitroprusside. As we have shown previously, all reflex heart rate responses were initially smaller in 15-month old than in 5-month old rats. Osmotic minipumps filled with saline or verapamil (100 micrograms/kg/day) were connected to cannulas in a lateral ventricle or femoral vein and, after 6 days, baroreflexes were recorded again. Control infusions of either saline intracerebroventricularly or verapamil intravenously were ineffective. In contrast, intracerebroventricular infusions of verapamil attenuated reflex heart rate responses to methoxamine or sodium nitroprusside differently in the two age groups: both reflex tachycardia and bradycardia were attenuated in 5-month-old rats; however, in 15-month-old rats only reflex bradycardia was reduced, whereas reflex tachycardia was unaffected. The selective reduction of reflex tachycardia in 5-month-old, but not in 15-month-old, rats suggests that intracerebroventricularly infused verapamil affects central baroreflex regulation differently depending on age. PMID- 2329503 TI - Centrally active antimuscarinic analogs of oxotremorine selectively block physostigmine-induced hypertension, but not peripheral muscarinic vasodepression. AB - Some tertiary antimuscarinic amines related to oxotremorine were compared with atropine and scopolamine for their ability to block physostigmine-induced hypertension and acetylcholine-induced hypotension in rats. These cardiovascular responses are mediated via muscarinic receptors in the brainstem and on the vasculature, respectively. In urethane-anesthetized rats, physostigmine (77 nmol/kg i.v.) increased mean arterial pressure 40 +/- 5 mm Hg. One hour later, each rat received a single dose of antimuscarinic, then a second bolus of physostigmine 10 min later. Linear regression analysis of antagonist dose-percent inhibition curves showed that all the agents inhibited physostigmine's pressor effect, thus indicating an ability to antagonize brain muscarinic receptors. BM-5 and BoK-1 were estimated to be equipotent with atropine, all having 50% inhibitory doses (ID50) in the 1.5 to 1.8 mumol/kg range. BR-370 and DKJ-21 were 3- and 30-fold less potent, respectively, than atropine in this assay, while scopolamine was the most potent (ID50: 0.039 mumol/kg). In contrast with atropine and scopolamine, the oxotremorine analogs possessed selective central antimuscarinic effects and were completely unable to antagonize the peripheral depressor response. Like atropine, only BM-5 showed significant tachycardiac effects, which suggested that this agent possessed affinity for myocardial muscarinic receptors. These findings support the concept that congeners of oxotremorine behave as centrally selective antimuscarinics at doses which have low peripheral antimuscarinic activity in vivo. This unique pharmacological profile makes them novel probes to study central cholinergic muscarinic mechanisms in cardiovascular regulation. PMID- 2329504 TI - Different patterns of autonomic nerve activity produced by a polar vs. a neutral cardiac glycoside. AB - Digitalis agents react with various peripheral reflex receptor areas (i.e., carotid artery baroreceptors and cardiac mechanoreceptors) to alter autonomic nerve activity. Physical characteristics of these reflex receptors differ and thus they may respond differently to polar and neutral cardenolides. Our purpose was to determine the effect of progressive i.v. infusion of either ASI-222, a polar aminocardenolide agent, or digoxin, a neutral cardenolide, on cardiac sympathetic, efferent vagal, and carotid sinus nerve activity. Digoxin or ASI-222 were infused into anesthetized dogs at dose rates which caused cardiac arrhythmias in about 2 hr. Nerve activities were monitored and recorded by a system of differential amplifiers and by a digital storage oscilloscope. Infusion of ASI-222 progressively reduced sympathetic nerve activity (approximately 55%) through the toxic dose; sympathetic nerve activity remained depressed even through the onset of cardiac arrhythmias. Digoxin also depressed cardiac sympathetic nerve activity but only at intermediate dose levels; sympathetic activity rose near the toxic dose. Digoxin increased both carotid sinus and vagal efferent nerve activity with progressive doses. In contrast, ASI-222 did not alter carotid sinus and efferent vagal nerve activity. In summary, digoxin activates carotid sinus baroreceptors; ASI-222 does not. Digoxin and ASI-222 produce different profiles of changes in cardiac autonomic nerve activity and appear to differ in autonomic reflex receptor interactions. PMID- 2329505 TI - Activation of protein kinase C inhibits internalization and downregulation of muscarinic receptors in 1321N1 human astrocytoma cells. AB - The effects of the protein kinase C activator phorbol 12-myristate, 13-acetate (PMA) on muscarinic receptor downregulation and internalization in 1321N1 human astrocytoma cells were determined. Downregulation was assessed by measuring [3H] quinuclidinyl benzilate binding to intact cells. PMA alone did not induce muscarinic receptor downregulation but instead decreased markedly both the rate and final extent of downregulation induced by the agonist carbachol. The specificity of various analogs for inhibiting carbachol-induced downregulation indicated involvement of protein kinase C. Furthermore the protein kinase C inhibitor staurosporine prevented the inhibitory effect of PMA on downregulation. In contrast, staurosporine did not inhibit agonist-induced downregulation. Neither agonist-induced downregulation nor the inhibitory effect of PMA were blocked by cycloheximide, indicating that protein synthesis is not required for these effects. Muscarinic receptor internalization was assessed both by sucrose density gradient centrifugation assays of receptor subcellular distribution and by measuring binding of the hydrophilic radioligand N-[3H]methylscopolamine to intact cells at reduced temperature. PMA did not induce muscarinic receptor internalization but rather inhibited internalization induced by the agonist carbachol. Together these results suggest that activation of protein kinase C leads to inhibition of an agonist-induced increase in the rates of muscarinic receptor internalization and degradation that are presumably responsible for receptor redistribution and eventual downregulation. PMID- 2329506 TI - Maternal age and blood alcohol concentration in the pregnant Long-Evans rat. AB - Despite comparable alcohol consumption, not all women who drink excessively give birth to children with fetal alcohol effects or the fetal alcohol syndrome. Various maternal factors may be important in this regard. For example, two recent animal studies found that maternal age was an important risk factor in regard to alcohol's adverse effects on pregnancy. Specifically, alcohol produced greater maternal and fetal toxicity in older and middle-age mothers than in younger cohorts. An age-related difference in maternal blood alcohol concentrations (BACs), despite comparable alcohol administration, may have been the major factor. That is, older mothers may achieve higher BACs or take longer to eliminate alcohol from their blood, resulting in greater maternal and fetal toxicity. The present study was conducted to investigate this possibility. Dams were of three age groups: 2 1/4, 3 3/4 and 5 1/4 months old. Alcohol (3.5 g/kg p.o.) was administered twice daily at a 6-hr interval from gestation days 11 to 19. Blood samples were obtained on gestation day 19 at 1, 2, 4 and 6 hr after each injection. The data showed a progressive increase in peak BACs and a prolonged presence of alcohol with increasing maternal age. It was subsequently hypothesized that age-related differences in percent body water content might account for these effects, and we tested for this possibility. While age-related differences in body water content were found, administering alcohol doses on the basis of body water content did not equate BAC curves across the maternal age groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329507 TI - Endothelial nitric oxide generating enzyme(s) in the bovine aorta: subcellular location and metabolic characterization. AB - The metabolic production of nitric oxide (NO) from bovine endothelial homogenates and subcellular fractions was examined. NO was quantified using a sensitive and specific ozone redox-chemiluminescence detector. Endogenously produced NO was detected in the headspace gas of bovine vascular endothelial homogenates supplemented with superoxide dismutase and an NADPH regenerating system, which had been incubated at 0 degrees C for 3 hr. An identical system incubated at 37 degrees C for 3 hr did not produce NO. Both superoxide dismutase and an NADPH regenerating system were required for observing endogenous NO production from endothelial homogenates. Among the various endothelial subcellular fractions tested, only the 1000 x g supernatant manifested significant generation of endogenous NO. Addition of 1.4 mM L-arginine (but not D-arginine, L-citrulline or L-lysine) resulted in significant enhancement of NO production from the 15,500 and 210,000 x g pellet fractions. L-arginine did not stimulate NO production from either homogenates or subcellular fractions of coronary vascular smooth muscle cells. Exogenously added calcium or magnesium was not required for NO generation in the 210,000 x g pellet stimulated with L-arginine, whereas L-canavanine (1.4 mM) and SKF 525-A (0.1 mM) significantly inhibited NO production with this preparation. Analysis of the enzyme marker data from various subcellular fractions suggests that the endothelial NO-generating enzyme system is membrane bound and might be associated with the plasma membrane. PMID- 2329508 TI - [Tyr0]-calcitonin gene-related peptide 28-37 (rat) as a putative antagonist of calcitonin gene-related peptide responses on opossum internal anal sphincter smooth muscle. AB - The effects of calcitonin gene-related peptide (CGRP) I(alpha) (human), CGRP II(beta) (human), CGRP (rat), and [Tyr0]-CGRP (rat) on the resting tone of opossum internal anal sphincter (IAS) were studied. Different CGRPs identified above produced a concentration-dependent fall in the resting tension of the IAS. CGRP II (human) was most potent, while [Tyr0]-CGRP (rat) was the least. The fall in IAS tension caused by CGRP II (human) was not modified by the neurotoxin tetrodotoxin, beta adrenoceptor antagonist propranolol and prostaglandin synthesis inhibitor indomethacin. In contrast to the other CGRP analogs, [Tyr0] CGRP 28-37 (rat) produced no significant effects on the resting tension of the IAS. However, the fragment caused significant rightward shifts in the concentration-effect curves of different CGRP analogs examined on the IAS. [Tyr0] CGRP 28-37 (rat) was found to be almost equipotent in antagonizing the inhibitory effects of CGRP (rat) and [Tyr0]-CGRP (rat), but was approximately 12 and 4 times more potent in antagonizing the responses of CGRP I (human) and CGRP II (human), respectively, as compared to that of CGRP (rat) and [Tyr0]-CGRP (rat). Calcitonin, on the other hand, caused a rise in the IAS tension by its action directly at the smooth muscle and this was not modified by [Tyr0]-CGRP 28-37. Thus, we conclude that: 1) CGRP causes a fall in the resting tension of IAS by its action directly at the smooth muscle; 2) [Tyr0]-CGRP 28-37 (rat) may serve as an antagonist of CGRP responses and 3) CGRP and calcitonin produce opposite actions on the resting IAS tension by the activation of their own receptors at the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329509 TI - Effects of plasma protein binding displacement on the pharmacokinetics, tissue and tumor concentrations and efficacy of brequinar, a highly protein-bound antitumor agent. AB - Brequinar is a developmental antitumor agent which is highly bound to plasma proteins. The effects of plasma protein binding displacement on brequinar pharmacokinetics, tissue distribution, tumor distribution and antitumor efficacy were evaluated. Sodium salicylate and ibuprofen increased the percentage of free brequinar in serum in vitro, in proportion to their added concentrations. Sodium salicylate also altered the pharmacokinetics of i.v. brequinar in rats when adminstered i.v. or p.o. at 10- or 50-fold higher doses than brequinar. At the highest salicylate/brequinar dose ratio, significant increases were observed for terminal half-life, mean residence times in the body and tissues, systemic clearance, distribution clearance, the volume of the central compartment and volume of distribution at steady state. Neither salicylate nor ibuprofen increased brequinar concentrations in lung and muscle specimens from rats, 4 or 24 hr after dosing. Tumor, lung and muscle brequinar concentrations in mice were also unaffected by coadministered sodium salicylate, 4 or 24 hr after a single i.v. brequinar dose. In rats infused for 48 hr with brequinar or brequinar plus salicylate, salicylate increased the percentage of free brequinar in plasma and lungs, but total brequinar concentrations were reduced. Antitumor efficacy was evaluated by measuring the survival times of mice implanted with L1210 leukemia cells. Salicylate-treated mice had a similar brequinar dose/response profile as mice not coadministered salicylate. Ibuprofen also did not increase brequinar's antitumor potency. PMID- 2329510 TI - Operant acquisition of alcohol by women. AB - Alcohol acquisition and use patterns were studied in 26 women on a clinical research ward. Women could earn alcohol (beer, wine or distilled spirits) or 50 for 30 min of performance on a second-order fixed ratio 300 (fixed interval 1 sec: S) schedule of reinforcement. Points earned for money and for alcohol were not interchangeable. A 7-day drug-free base line was followed by 21 days of alcohol availability and a postalcohol drug-free period of 7 days. Heavy, moderate and occasional drinkers differed significantly in the average number of alcohol drinks purchased (P less than .001). Five heavy drinkers purchased an average of 164 (+/- 14) drinks during the study; 12 moderate drinkers purchased an average of 80 (+/- 4) drinks; 9 occasional drinkers purchased an average of 26 (+/- 4) drinks. Individual drinking patterns fluctuated markedly from day-to-day. Daily peak blood alcohol levels (milligrams per deciliter) were significantly correlated with variations in daily drinking patterns in 22 of the 26 subjects (P less than .02-.0001). Computer analysis of daily alcohol consumption patterns (alcohol peak frequency and peak amplitude) showed that moderate drinkers had significantly more peaks in alcohol consumption than occasional drinkers (P less than .05). The average number of drinks constituting each peak was significantly greater for the heavy and moderate drinkers than for the occasional drinkers (P less than .05). The interval between successive peaks in alcohol consumption averaged 4.6 (+/- 0.8) days for the occasional drinkers, 3.2 (+/- 0.2) days for the moderate drinkers and 3.6 (+/- 0.17) days for the heavy drinkers but these differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329511 TI - Calcium antagonists show two modes of protection in ischemic heart failure. AB - Retrogradely perfused, isovolumically beating, paced rat hearts were subjected to 30 min of global ischemia in the absence and presence of nifedipine, verapamil, bepridil and quaternary bepridil at a concentration ranging from 3 to 10,000 nmol/l. Under constant pressure conditions, the arrest of coronary flow and the reduction of ventricular contraction during global ischemia were readily reversible and quickly returned at reperfusion. During ischemia, however, a diastolic contracture developed, which was slowly reversible upon reperfusion. The calcium antagonists studied appeared to delay and diminish in a concentration dependent way the diastolic contracture during ischemia. Furthermore, they accelerated the reduction of this contracture at reperfusion. Nifedipine, bepridil and quaternary bepridil showed a 100 to 1000 times higher potency in accelerating the recovery of the diastolic contracture during the reperfusion phase than in reducing the development of diastolic tension during the ischemic period itself, whereas verapamil hardly discriminated these two phases. When the hearts were reperfused with nifedipine under constant flow conditions, reduction of the diastolic contracture during ischemia could still be observed, but the accelerated reduction of end-diastolic pressure during reperfusion was no longer present. The results are discussed in relation to the energy saving, negative inotropic activity of the drugs before the ischemic period and the strong coronary vasodilation, which seems to be involved in the protective activity of the drugs, especially during reperfusion. PMID- 2329512 TI - Eltoprazine suppresses hyperpolarizing responses to serotonin in rat hippocampus. AB - In this study we report the effects of eltoprazine, a phenylpiperazine derivative with high affinity for 5-hydroxytryptamine1 (5HT1) binding sites, on membrane properties of hippocampal neurons. Intracellular recordings were made from cornus ammoni-1 pyramidal neurons in rat hippocampal slices. Responses to eltoprazine were compared with 5HT-induced responses. Superfusion with 5HT induced a dose dependent hyperpolarization of the membrane accompanied by a resistance decrease. Eltoprazine evoked membrane changes that were similar to but much weaker than those induced by 5HT. Both the 5HT- and eltoprazine-evoked membrane hyperpolarizations were largely suppressed in the presence of spiperone. The eltoprazine-induced effects persisted in the presence of tetrodotoxin and tetraethylammonium and also when haloperidol and phentolamine were added to the medium, indicating that the small agonistic effects of eltoprazine are not due to an indirect activation of dopamine or alpha adrenergic receptors. Superfusion with eltoprazine furthermore resulted in a marked reduction of the response to concomitantly applied 5HT. Dose-response curves for 5HT were shifted to the right in the presence of eltoprazine, while the maximal response was diminished. Hyperpolarizations induced by baclofen, which presumably activates the same K+ conductance as 5HT, were not significantly reduced by eltoprazine. Our data, added to the previously demonstrated high affinity of eltoprazine for 5HT1 sites, suggest that in the hippocampal cornus ammoni-1 area eltoprazine acts as a partial 5HT1 agonist with a relatively low intrinsic activity but a considerable potency to suppress hyperpolarizing responses to 5HT. PMID- 2329513 TI - Assessment of cyclosporine A interactions with human plasma lipoproteins in vitro and in vivo in the rat. AB - The interaction of cyclosporine A (cyclosporine) with human plasma lipoproteins has been investigated by combining in vitro and in vivo methods. Binding parameters were derived in vitro from an erythrocyte partitioning method, and provided reliable Ka (product of the number of binding sites by the association constant) estimates: high-density lipoprotein, 2.21 +/- 0.48; low-density lipoprotein, 1.23 +/- 0.12; and very low-density lipoprotein, 0.53 +/- 015 liters/g, showing that high-density lipoprotein was the major carrier of plasma cyclosporine. The effects of cyclosporine binding to lipoproteins were investigated in vivo by the intracarotid injection technique of Oldendorf in the rat. The brain extraction of cyclosporine was related inversely to the lipoprotein concentration in the injected solution, allowing estimation of nKa in vivo: high-density lipoprotein, 2.25 +/- 0.59; low-density lipoprotein, 0.62 +/- 0.13; and very low-density lipoprotein, 0.57 +/- 0.14 liters/g. This showed that brain uptake occurred from the free drug pool and possibly from a small part of the originally lipoprotein-bound pool of cyclosporine, at least for low-density lipoprotein-bound cyclosporine. These results allow the calculation of an index of the unbound plasma cyclosporine fraction. PMID- 2329514 TI - In vivo evidence for carrier-mediated uptake of beta-lactam antibiotics through organic anion transport systems in rat kidney and liver. AB - The transport mechanisms of beta-lactam antibiotics in the rat kidney and liver were studied with an in vivo tissue-sampling single-injection technique using [3H]benzylpenicillin [( 3H]PCG) as a substrate. Concentration-dependent uptake of [3H]PCG was observed in the kidney, and the in vivo kinetic parameters were estimated as follows: the maximum uptake rate (Jmax) was 6.88 mumol/min/g of kidney, MIchaelis constant (Kt) was 1.39 mM and nonsaturable first-order rate constant (kd) was 0.414 ml/min/g of kidney. The uptake of [3H]PCG was inhibited by organic anions but not by organic cations. Several beta-lactam antibiotics also reduced the uptake of [3H]PCG. Furthermore, the organic anion, probenecid, and beta-lactam antibiotic, cefpiramide, showed a dose-dependent inhibitory effect. These results suggest participation of an organic anion transport system in uptake of beta-lactam antibiotics across the renal plasma membrane. Saturable uptake of [3H]PCG was also observed in the liver and Jmax, Kt and Kd were estimated to be 3.62 mumol/min/g of liver, 3.59 mM and 0.223 ml/min/g of liver, respectively. The in vivo influx rate calculated from Jmax/Kt in the liver was 1.01 ml/min/g of liver and was close to the in vitro value, 1.54 ml/min/g of liver, estimated previously from isolated hepatocytes. Although dipeptides and organic cations showed no effect on the hepatic uptake of [3H]PCG, probenecid significantly reduced its uptake. Several beta-lactam antibiotics also reduced the uptake of [3H]PCG by the liver. These features of the hepatic uptake of beta lactam antibiotics through an organic anion transport system are in agreement with the previous results obtained in isolated hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329515 TI - Effect of lithium on renal transport and utilization of alpha-ketoglutarate in the rat. AB - Experiments were carried out in the intact functioning rat kidney to study the effect of lithium on both the renal transport of alpha-ketoglutarate (alpha-KG) along the nephron by micropuncture techniques and the renal uptake and peritubular transport of alpha-KG by measuring the renal blood flow, the urinary flow and the rate of renal alpha-KG delivery, filtration, reabsorption or secretion and excretion. At endogenous plasma alpha-KG concentration, 2.3 mM plasma lithium caused an increase in the fractional excretion of alpha-KG, whereas 4.6 mM plasma lithium led to a net secretion of alpha-KG. The micropuncture data indicate that this secretion occurred between the late proximal and the distal tubule, i.e., in the pars recta and/or in the loop of Henle. When plasma alpha-KG concentration was elevated, the two doses of lithium used inhibited the reabsorption of alpha-KG both in the proximal tubule and in the pars recta and/or the loop of Henle. Renal arteriovenous measurements reveal that, at low plasma alpha-KG concentrations, lithium caused a significant decrease in both the renal uptake of alpha-KG and the peritubular transport of this organic anion. These results suggest that the alpha-KG secreted in the pars recta and/or the loop of Henle was synthesized within the renal cells of the latter segments and not transported from the blood to the tubular lumen. At higher plasma alpha-KG concentrations, both the peritubular transport and the renal reabsorption were reduced by lithium. PMID- 2329516 TI - Platelet-activating factor antagonists treatment protects against postischemic acute renal failure in rats. AB - Platelet-activating factor (PAF-acether) has been shown to be produced by the kidney and to sharply reduce glomerular filtration rate (GFR) and renal plasma flow (RPF). Thus, PAF-acether could be a possible mediator of the reduction of GFR and RPF in ischemic-induced acute renal failure (ARF). We have assayed the effect of inhibiting the interaction of PAF-acether with its receptor using two specific PAF-acether antagonists, BN-52021 and alprazolam, on the evolution of the GFR and RPF, in the experimental model of ARF induced in rats by clamping the left artery for 60 min. In addition, we have measured arteriovenous differences in PAF-acether concentration, as well as PAF-acether content in glomeruli from rats with ARF pretreated or not with BN-52021. In metabolic cage studies, plasma creatinine increased more in the untreated than in the BN-52021-treated group, whereas creatinine clearance was higher in treated than in untreated rats. In acute clearance experiments, after renal artery clamping, untreated rats showed a marked oliguria and reduction of the inulin clearance (greater than 99%), which showed no recovery 90 min after clamp release, whereas GFR reached values above 0.1 ml/min in the rats treated with BN-52021 or alprazolam, with clearly significant statistical differences. Results of p-aminohippurate clearance were similar to those of GFR. Glomeruli from rats with ARF had greater amounts of PAF acether than glomeruli from normal rats, whereas glomeruli from BN-52021-treated rats with ARF produced intermediate amounts. These results provide evidence for a role for PAF-acether in the genesis of this model of experimental ARF. PMID- 2329517 TI - Mechanisms of amphotericin B-induced reduction of the glomerular filtration rate: a micropuncture study. AB - Amphotericin B infusions cause acute reductions in renal plasma flow and glomerular filtration rate. The exact mechanism by which these changes occur has not been identified fully, nor have the effects of the drug on the renal microcirculation been studied adequately. In this study, we examined the effect of intrarenal amphotericin B infusions (0.05 mg/kg/min) on glomerular hemodynamics in the anesthetized rat. Amphotericin B did not affect systemic blood pressure and slightly increased hematocrit (5%), but significantly decreased renal blood flow and glomerular filtration rate by 40 and 35%, respectively. Glomerular micropuncture revealed decreases in single nephron plasma flow and glomerular filtration rate (from 142 +/- 12 to 89 +/- 14 and from 35.3 +/- 2.2 to 22.8 +/- 2.8 nl/min, respectively). These changes were due to significant increases in pre- and postglomerular resistances (from 1.91 +/- 0.17 to 3.95 +/- 0.38 and from 1.30 +/- 0.10 to 2.08 +/- 0.12 10(10) dyn.sec.cm-5, respectively), and to a significant decrease in the glomerular capillary ultrafiltration coefficient which fell from 0.043 +/- 0.008 to 0.032 +/- 0.009 nl/(sec.mm Hg). These results provide further insight into the mechanisms of the acute renal effects of amphotericin B, and suggest possible mediators that may be involved in these effects. PMID- 2329518 TI - Autonomic modulation of the frequency-dependent actions of diltiazem on the atrioventricular node in anesthetized dogs. AB - Calcium antagonists have rate-dependent effects on atrioventricular node refractoriness in autonomically blocked dogs. Autonomic reflexes can attenuate diltiazem's actions and could alter their frequency-dependence. We evaluated the effects of four steady-state drug concentrations in each of seven dogs with intact autonomic tone, six with muscarinic blockade (atropine) and eight with combined muscarinic and beta adrenergic blockade. Diltiazem depressed atrioventricular nodal function less in autonomically intact dogs than in the other two groups. The concentration-response relationship for increases in Wenckebach cycle length (compared to intact dogs) was twice as steep among dogs with muscarinic blockade (P less than .001) and three times as steep with combined blockade (P less than .001). For an equal dose of diltiazem, the slope of drug-induced refractory period prolongation vs. pacing cycle length was similar (-0.20 +/- 0.11%/msec, mean +/- S.D.) in intact dogs compared to atropinized dogs (-0.21 +/- 0.10%/msec) and dogs with combined blockade (-0.24 +/ 0.14%/msec). Amplification of diltiazem's actions by the rapid atrial rate during atrial fibrillation was associated with increases in mean RR interval which were 8.3 times as large as changes in refractory period produced by the drug at slow heart rates. We conclude: 1) autonomic reflexes reduce diltiazem's effect for any given plasma concentration; 2) changes in vagal tone can play an important role in the autonomic response to diltiazem; and 3) despite altering the magnitude of diltiazem's effects, autonomic mechanisms do not prevent frequency-dependent drug action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329519 TI - Alteration of plasma sex hormone levels associated with old age and its effect on hepatic drug metabolism in rats. AB - A mechanism of age-associated alterations in plasma sex hormone levels as well as their effect on drug metabolizing enzyme activities were studied using male and female Fischer 344 rats of ages ranging between 3 and 30 months. Plasma testosterone levels as well as the activity of the rate limiting enzyme required for testosterone production in testes, androstenedione 17 beta-oxido-reductase, decreased with senescence in parallel with the alteration of drug metabolism whereas activity of hepatic microsomal androstenedione 5 alpha-reductase, the testosterone metabolizing enzyme, increased with age. The profile of drug metabolizing activities with imipramine, diazepam, hexobarbital, lidocaine, p nitroanisole and androstenedione as substrates in old (27-month-old) male rats was almost identical to that in young or old female rats, indicating that neonatal androgenic imprinting of drug metabolism in male rats was erased in senescence. Castration of adult (9-month-old) male rats caused a decrease in drug metabolism, but did not result in complete feminization of the profiles of drug metabolism as was observed in old male rats, indicating that neonatally imprinted male pattern of drug metabolism was still retained in the absence of testosterone in adult male rats. Testosterone administration restored completely male-level activities in castrated adult rats, but caused only a partial recovery in old male rats. It is proposed that senescence associated feminization of the drug metabolizing ability of the male rat liver may be in part due to the decrease in testosterone levels in old age and in part to the loss of neonatal imprinting. PMID- 2329520 TI - Persistence of neurochemical changes in dopamine systems after repeated cocaine administration. AB - The purpose of this study was to test whether persistent changes consistent with behavioral sensitization occur in dopamine (DA) uptake, release or receptors following repeated cocaine administration. Our neurochemical experiments focused primarily on the striatum; however, quantitative autoradiography was used to measure D-1 and D-2 DA receptors in both cell body and terminal regions of the nigrostriatal and mesolimbic dopaminergic pathways. After receiving eight once daily injections of cocaine (10 mg/kg, i.p.), rats remained behaviorally sensitized for 1 week. This repeated treatment with cocaine induced two changes consistent with increased dopaminergic transmission. Postsynaptic D-2 DA receptors were selectively increased in nucleus accumbens one day after termination of the repeated cocaine administration; however, these receptors returned to control levels one week after cocaine administration had been terminated. In contrast, amphetamine-stimulated [3H] DA release from striatal slices was increased in rats receiving repeated cocaine injections, but this increase was not apparent until 1 week after the drug administration had been terminated. While neither of these two changes is sufficient to explain cocaine induced behavioral sensitization, both are consistent with increased dopaminergic responsiveness and may contribute to sensitization. PMID- 2329521 TI - Cytochrome P 450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues. AB - The organ distribution of microsomal cytochrome P 450 isoenzymes (P 450), microsomal epoxide hydrolase (EH) and cytosolic glutathione-S-transferases was investigated by immunoblotting and enzyme measurements in rats and humans. In rats, P 450 IA1 was detected only in the duodenum, and P 450 IA2 and IIC11 were detected only in the liver. The highest concentrations of P 450 IIB1/B2 were found in the lung and in the duodenum; pentoxyresorufin-O-dealkylase activity was closely correlated with the amounts of P 450 IIB1/B2 in the different organs. P 450 IIE1 was present in liver, kidney and lung, whereas EH was found in liver, intestine and kidney. In humans, P 450 IIIA4 was detected in all tissues investigated; the highest concentrations were found in liver and intestine. The P 450 IIIA4 level was closely correlated with that of erythromycin demethylase and pentoxyresorufin-O-dealkylase activities. P 450 IIC8-10, IIE1 and IID6 were expressed in liver and intestine, P 450 9 in liver and kidney and P 450 IA2 in liver. EH was identified only in liver, intestine and kidney. In both species, concentrations and total amounts of P 450 isoenzymes and EH were much lower in all extrahepatic tissues than in the liver. Conversely, glutathione-S-transferase pi was abundant in human intestine and colon compared to liver. Glutathione-S transferase-mu polymorphism was confirmed in all tissues investigated. This extensive study showed that the pattern of (iso) enzymes was different in all tissues studied; consequently, xenobiotic metabolism would appear to be very different in each type of tissue. PMID- 2329522 TI - Muscarine depolarizes rat substantia nigra zona compacta and ventral tegmental neurons in vitro through M1-like receptors. AB - Intracellular recordings were made from presumed dopamine-containing neurons in slices of rat mesencephalon. Muscarine (3-100 microM) increased the rate of spontaneous action potentials; it also caused a membrane depolarization and, in voltage-clamp, an inward current. Concentration-effect curves to muscarine were shifted rightwards by pirenzepine (0.03-1 microM) with an estimated KD of 14 nM. The inward current caused by muscarine was voltage-dependent. Between about -50 and (-)-65 mV it was associated with a decrease in membrane conductance, but between -70 and -110 mV it was unaccompanied by any change in membrane conductance. Muscarine was without effect on the action potential afterhyperpolarization, or on a slowly developing inward current evoked by step hyperpolarizations of up to 20 mV from -45 mV. Muscarinic depolarizations or inward currents were reduced reversibly or abolished by a low calcium (0.25 mM)/high magnesium (10 mM) solution. It is concluded that muscarinic excitation of dopaminergic neurons is mediated by M1-like receptors. PMID- 2329523 TI - Heterogeneity of high-affinity nicotinic [3H]acetylcholine binding sites. AB - Studies were conducted on high-affinity, nicotinic binding of 3H-labeled acetylcholine ([3H]ACh) to membrane preparations derived from the TE671 human clonal line and the PC12 rat pheochromocytoma. For comparative purposes and to extend results obtained by others in previous studies, [3H]ACh binding to membrane preparations derived from rat brain and from the electric tissue of Torpedo californica also was characterized. In each case, specific [3H]ACh binding (KD values of about 10 nM) could be fit by linear Scatchard and logit-log curves (slope of the latter of about 1.0) indicating that binding occurred to a single class of noninteracting sites, except that a better fit to PC12 cell membrane binding data was obtained using a two-site model. Quantitation of high affinity binding sites for [3H]ACh and radiolabeled alpha-bungarotoxin and studies of unlabeled toxin competition for [3H]ACh binding indicated that toxin and agonist sites on TE671 cell or Torpedo membranes were closely related, but that toxin and agonist sites had limited or no physical overlap on PC12 cell or rat brain membranes. Generally, drugs of the bisonium and bis-choline series were more effective inhibitors of [3H]ACh binding to TE671 cell or Torpedo membranes, but nicotine and cytisine interacted with PC12 cell or rat brain sites with highest affinity. These results suggest that nicotinic agonists bind with high affinity to specific, membrane-bound sites on presumptive nicotinic ACh receptors expressed on each of these preparations. Moreover, the data are consistent with structural heterogeneity of these nicotinic receptor sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329524 TI - Differential regulation of heme and drug metabolism in rat testis and prostate: response to cis-platinum and human chorionic gonadotropin. AB - In the absence of notable changes in heme metabolic activities in the testes of rats treated with cis-platinum (7 mg/kg i.v.) and sacrificed after 1, 3 or 7 days, time-dependent decreases in the activity of benzo(a)pyrene hydroxylase (AHH), ethoxyresorufin O-deethylase (7-ERDE) and the concentration of cytochrome P-450 were observed. In contrast, in the prostate of the treated rats, despite reductions in the activity of heme oxygenase and that of enzymes of heme biosynthetic pathway, biotransformation of benzo(a)pyrene and ethoxyresorufin and cytochrome P-450 concentration were not altered. cis-Platinum treatment (7 days) also decreased markedly the serum and testicular testosterone levels (50-70%). Human chorionic gonadotropin (hCG, 25 IU/100 g/day for 7 days) given to the treated rats (7 days) caused a 5- to 15-fold increase in the serum and testicular testosterone levels and reversed the spectrum of the aforementioned inhibitory effects of cis-platinum on heme metabolic enzymes. The response of the testis and prostate drug metabolic activities to hCG treatment also differed. In the testis of cis-platinum-treated rats, the inhibited AHH and 7-ERDE activities were reversed by hCG treatment and cytochrome P-450 concentration returned to the control level. In the prostate, however, hCG treatment neither changed AHH and 7 ERDE activities nor the concentration of the microsomal cytochrome P-450. In addition, in the testis the pattern of response of AHH and 7-ERDE activities to hCG was dissimilar; whereas 7-ERDE activity returned to the normal level, AHH activity surpassed the normal activity and reached a near 2.5-fold increase over the control value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329525 TI - Effect of phenylpiperidine opioid antagonists on food consumption and weight gain of the obese Zucker rat. AB - Meal-fed Zucker rats were used to determine the acute and chronic s.c. effect of certain trans-3,4-dimethyl-4-phenylpiperidines (opioid antagonists) on food consumption. In acute studies, the active compounds suppressed food intake significantly of lean and obese meal-fed Zucker rats. LY117413 was the most effective over the 4-hr period immediately after the s.c. administration of the drug. Long-term chronic s.c. administration to the meal-fed obese Zucker rat showed that LY88329 and LY117413 significantly reduced food consumption for as long as the drug was administered and resulted in a significant decrease in body weight gain when compared to nontreated control obese rats. There was no evidence for the development of tolerance to these effects of LY88329 and LY117413 in this genetically obese rat model. PMID- 2329527 TI - Morale levels. PMID- 2329526 TI - Electrophysiological evidence that ethanol alters function of medial septal area without affecting lateral septal function. AB - Evidence is provided in this manuscript that ethanol acts directly on neurons in the medial septal area (MSA). Initially, the electrophysiological characteristics of MSA neurons in freely moving rats were characterized and found similar to that observed in rats anesthetized with urethane, but not chloral hydrate. Therefore, urethane was used to evaluate the effects of ethanol in anesthetized rats. The conclusion that ethanol influences neural function in the MSA is based on electrophysiological data that ethanol (0.75-3.0 g/kg i.p.) suppresses neural firing of medial septal cells in urethane-anesthetized as well as in unanesthetized rats in a dose-related fashion. Concurrent with the suppression of firing rate, the rhythmic bursting pattern of activity of MSA neurons is disrupted by ethanol. The changes observed in the MSA could not be attributed to an indirect action of ethanol on afferents from the lateral septum to the MSA, because ethanol did not alter neural activity of cells in the lateral septum. These data indicate that ethanol does not have a common action on all neurons. Neural activity in the MSA recovered from the acute action of ethanol at a time when blood ethanol levels were near maximal, indicating an acute tolerance to this effect of ethanol. The time course of change in neural activity in the MSA was highly correlated with the time course of a measure of behavioral sedation, but not the hypothermia produced by ethanol. Thus, the work in this manuscript supports the view that ethanol has selective actions on MSA neurons in the rat septal area and that these actions may influence the behavioral sedation induced by ethanol. PMID- 2329528 TI - Positive assessment. PMID- 2329529 TI - Working with combating stress. PMID- 2329530 TI - Working with the patient and the family. PMID- 2329531 TI - Your CE topic (No. 110). Introduction to transdermal drug delivery systems (Part I). PMID- 2329532 TI - How the environment affects turnover. PMID- 2329533 TI - LPN to ADN. PMID- 2329534 TI - Psychosocial implications of lung cancer. PMID- 2329535 TI - Gardenias & love. PMID- 2329536 TI - Protect the licensed practical-vocational nurse. PMID- 2329537 TI - Prototype AIDS vaccine works in monkeys. PMID- 2329538 TI - An experimental study on the influence of the derived casts on the accuracy of different recording materials. Part II: Polyether, acrylic resin, and corrected wax wafer. AB - A specific testing system was used to determine the three-dimensional changes of interocclusal registration materials for a simulated patient and the derived stone casts. The results indicated that the deviations of the derived casts were more pronounced than the original models. There was great heterogeneity with all recording materials and the materials were not consistently accurate after limited storage of 30 minutes. PMID- 2329539 TI - Apparent density and tensile strength of materials for facially butted porcelain margins. AB - The study focused on comparison of the as-fired density and tensile strength of unmodified and modified porcelains used for construction of facially butted porcelain margins. The respective densities and tensile strengths of unmodified body and shoulder porcelains were found to be comparable. Also statistically equivalent were the measured properties of specimens made from either an unmodified shoulder-porcelain formulation or shoulder-porcelain powder--aqueous sodium silicate solution mixtures. On the other hand, the respective densities and tensile strengths of body porcelain-resin and shoulder porcelain-wax combinations were significantly lower (p less than 0.05) than those of their unmodified counterparts. Low density and tensile strength limit the rational use of wax or resin-modified porcelains to final bakes for correcting small, troublesome labiogingival discrepancies. PMID- 2329540 TI - Properties of cobalt-chromium metal ceramic alloys after heat treatment. AB - A comparison of mechanical properties of seven metal ceramic alloys in as-cast and heat-treated conditions resulted in significant differences. The alloys that were tested included seven cobalt-chromium metal ceramic alloys. Mechanical properties include strength, elongation, modulus of elasticity, and microhardness. Twenty-four tensile bars were cast for each alloy. Twelve of the 24 bars for each alloy were randomly selected for heat treatment with the Ceramco technique. Results indicated that the tested alloys had similar mechanical property values as a group in both the as-cast and the heat-treated conditions. The heat treatment had little effect on the cobalt-chromium alloys, although several did become significantly harder. In either condition, the cobalt-chromium alloys showed a high value of strength, a low percent of elongation, a high modulus of elasticity, and a high value of hardness. The high value of hardness and the low percent of elongation would make these alloys difficult to handle clinically. PMID- 2329541 TI - An evaluation of the surface characteristics of a facial prosthetic elastomer. Part III: Wettability and hardness. AB - Silicone facial prosthetic elastomers may cause tissue damage by abrasion. Such damage is a particular concern when prostheses are mechanically retained against tissues compromised by adjunctive therapy. The hardness and wettability of Cosmesil material was compared with that of Molloplast-B material. The stone test surfaces were separated with soap, sodium alginate, silicone paste, and left untreated. A polished stainless steel surface was prepared as a control. The specimens of Cosmesil and Molloplast-B materials were processed against each of these surfaces. Ten specimens of each material were processed against the five different surfaces. Wettability was evaluated by measuring the contact angle with a profile projector. Indentation hardness was measured with a Shore-A durometer. Statistical analysis involved multiple analyses of variation and Tukey's procedures (in all cases p less than 0.05). Molloplast-B material was found to have a higher wettability than Cosmesil material (means = 3.22 degrees higher); sodium alginate separator yielded silicone specimens with the highest wettability; Molloplast-B material was found to be harder than Cosmesil material (means = 9.75 Shore-A indentation units harder). The softest silicones were processed with soap separator. Silicone grease yielded the hardest specimens. The mechanical performance of Cosmesil material would be enhanced by increasing the surface wettability. The hardness of Cosmesil material is within the ideal range for a maxillofacial prosthetic elastomer. PMID- 2329542 TI - A new technique for making occlusal devices. AB - This procedure has an application to all types of occlusal devices. It is a novel combination of hard and soft acrylic resin. The outer shell of hard resin takes the abuse of the opposing occlusion. The thin well-controlled lining of soft resin makes it easier to seat and more comfortable to wear yet is thin enough that the entire device serves as if it were made entirely of hard acrylic resin. The detailed directions for the entire procedure make it possible to fabricate these novel devices without error. PMID- 2329543 TI - Cleaning the internal threaded chamber of osseointegrated implants. PMID- 2329544 TI - Preventing aspiration or ingestion of single fixed restorations. PMID- 2329545 TI - The versatile air abrasive blaster. AB - The air-abrasive blaster has become an indispensable tool in the prosthodontic laboratory. New uses are discovered daily. A number of them are described in this article. PMID- 2329546 TI - Production of IL-6 (BSF-2/IFN beta 2) by mononuclear cells in premature and term infants. AB - The production of interleukin 6 (IL-6) was examined in premature neonates (48 cases, including 3 miscarried fetuses) and fullterm neonates (20 cases). The IL-6 production by mononuclear cells was measured after stimulation with Staphylococcus aureus Cowan Strain I (SAC), phytohemagglutinin (PHA) or lipopolysaccharide (LPS). The production in full-term neonates was similar to that in healthy adults, whereas it was significantly lower in premature neonates without premature rupture of the membrane (PROM). However, in premature infants with PROM a normal level of IL-6 production was observed in mononuclear cells stimulated with SAC, PHA and LPS. Furthermore, there was a positive correlation between the IgM concentration in the cord serum and IL-6 production by LPS stimulated mononuclear cells. PMID- 2329547 TI - Lymphocyte subpopulations in lymph and blood draining from the uterus and ovary in sheep. AB - Lymphocyte subsets in utero-ovarian peripheral lymph and uterine and jugular venous blood were analysed with the aid of monoclonal antibodies, polyclonal antisera and flow microfluorometry. The proportion of various lymphocyte subpopulations, as determined by monoclonal antibodies (mAbs) and polyclonal antisera, was found to vary between utero-ovarian peripheral lymph and jugular and uterine venous blood. T cell levels were higher in utero-ovarian peripheral lymph (approx. 80% CD5+, 50% CD4+ and 23% CD8+) than peripheral blood (approx. 55% CD5+, 18% CD4+ and 12% CD8+). Conversely, in lymph, 10% of lymphocytes were B cells compared to 30% in blood. There were 20-30% MHC II+ cells in utero-ovarian peripheral lymph and 40-50% in blood. The level of CD45R+ cells in utero-ovarian peripheral lymph was low (2%) compared to peripheral blood (approx. 55% in pregnant and 25% in non-pregnant ewes). The proportion of lymphocyte subpopulations in lymph was similar for pregnant and non-pregnant ewes. However, some differences in levels in peripheral blood were evident between uterine and jugular venous blood and pregnant and non-pregnant ewes. CD4+ cells were higher in the uterine vein (14%) than in the jugular vein (11%) of pregnant ewes. The uterine and jugular veins in pregnant ewes contained approx. 50% MHC II+ cells compared to 30% in non-pregnant ewes. Likewise, the proportion of CD45R+ cells was higher in uterine and jugular venous blood of pregnant ewes (approx. 58%) compared to non-pregnant ewes (around 25%). PMID- 2329548 TI - Inhibition of binding of anti-CD3 antibodies to paternal lymphocytes correlates with failure of immunotherapy for treatment of recurrent spontaneous abortions. AB - A two color flow cytometry crossmatch (FCXM) was used to evaluate the induction of anti-lymphocyte antibodies in 34 women undergoing immunotherapy for recurrent spontaneous abortions. All women had anti-lymphocyte antibodies that reacted with T-cells when analyzed by FCXM. However, inhibition of the binding of anti-CD3 to paternal CD3 lymphocytes in the presence of maternal antipaternal lymphocyte antiserum was found for some couples following lymphocyte immunotherapy for spontaneous recurrent abortions. Ten couples who had another spontaneous abortion following immunotherapy showed inhibition. In contrast, eight couples who did not show inhibition of the binding of anti-CD3 T lymphocytes to paternal lymphocytes by maternal anti-lymphocyte antiserum had live births. Women of the remaining 16 couples were either pregnant and awaiting birth or not pregnant. Thus, by FCXM it may be possible to predict those couples who will have successful pregnancies following this treatment. PMID- 2329549 TI - Role of T cell subsets in the maternal-to-neonatal transmission of immunity against Trichinella spiralis during lactation in rats. AB - We have previously demonstrated the maternal-to-neonatal transfer of immunity to T. spiralis during lactation and have shown that antigen-specific T lymphocytes, when injected into the mother or orally fed to neonates, can mediate this transfer. To further analyze the T cell subsets involved in conferring this protection, T lymphocytes were isolated from the mesenteric lymph nodes of syngeneic donor rats infected 4-6 days earlier with T. spiralis. The T cells were incubated in vitro with either mouse-anti-rat 0X8 or W3/25 monoclonal antibody, "panned" on plates coated with goat-anti-mouse Ig, and the non-adherent T helper or T cytotoxic/suppressor cells harvested. 100 x 10(6) T helper cells were injected i.v. into mothers once in early lactation and again two days prior to challenging their pups (200 T. spiralis larvae) at 2 weeks of age. This resulted in significant passage of immunity from the mothers to their suckling neonates, worm counts being 59% and 73% of control values 3 and 8 days post-challenge (P less than 0.01). Injection of T-cytotoxic/suppressor cells using the same regimen resulted in significant suppression of immunity in challenged pups, who retained worm counts that were 105% and 145% of control values at 3 and 8 days post challenge. Synergy between recombined panned T-helper and T cytotoxic/suppressor cells without Ly1+2+3+ amplifier cells was tested by recombining non-adherent panned 0X8 and W3/25 cells. This resulted in no significant expressions of immunity in the pups when compared to controls. The presence of transferred maternal T cells within the neonate was evidenced by the fact that neonates (nursing on immune mothers) had significant (P less than 0.01) delayed footpad reactions to a crude T. spiralis antigen preparation, as compared with neonates nursing on non-immune controls. PMID- 2329550 TI - Prostaglandin-E2 released by pre-implantation human conceptuses. AB - This work investigates the production of prostaglandin E2 (PGE2), a well known modulator for the suppression of immune cells, by pre-implantation human conceptuses from the 4-cell stage to the hatched blastocyst and by cumulus oophorus cells, these being obtained from an IVF/ET program. Cumulus cell complexes cultured for 48 h produced considerable amounts of PGE2, necessitating complete removal of their influence on the conceptus cultures. All stages of the human conceptus studied produced PGE2 during 48-h cultures, the greatest amounts from late blastocysts, and from those cultured in media containing bovine serum albumin rather than human donor serum. Indomethacin-treated control blastocysts confirmed the synthesis and release from the human conceptuses. The production of PGF2a from human blastocysts could not be demonstrated. PMID- 2329551 TI - Cyclobut-A and cyclobut-G: broad-spectrum antiviral agents with potential utility for the therapy of AIDS. PMID- 2329552 TI - Hypoxia-selective antitumor agents. 4. Relationships between structure, physicochemical properties, and hypoxia-selective cytotoxicity for nitracrine analogues with varying side chains: the "iminoacridan hypothesis". AB - The nitroacridine derivative nitracrine is a potent hypoxia-selective cytotoxin for mammalian cells in culture. In an attempt to modulate the degree of hypoxia selectivity among this class of compounds, we have studied a series of side-chain analogues of nitracrine. Both the electronic and steric properties of the side chain are shown to be important in determining the hypoxia selectivity of the compounds, by controlling the degree of aminoacridine/iminoacridan tautomerism. Studies with the repair-defective Chinese hamster cell line UV4 indicate that the cytotoxicity of all the compounds is due to nitro group reduction and subsequent macromolecular adduct formation. However, compounds such as the 9-amino derivative, which exist totally as the aminoacridine tautomer, form much less lethal lesions than the 9-alkylamino derivatives, which exist to varying degrees in the iminoacridan conformation. For the whole set of compounds, the degree of hypoxia-selective cytotoxicity correlates well with the proportion of iminoacridan tautomer present. PMID- 2329553 TI - The discovery of potent nonpeptide angiotensin II receptor antagonists: a new class of potent antihypertensives. AB - A new class of potent antihypertensives has been discovered that exert their effect through blockade of the angiotensin II (AII) receptor. Most AII antagonists reported so far are peptide mimics of the endogenous vasoconstrictor octapeptide angiotensin II. The compounds of this paper are nonpeptides and therefore constitute a new class of potent AII receptor antagonists. Based on the overlap of a conformation of AII with literature lead 3, a hypothesis was developed suggesting the need for an additional acidic functionality to increase the lead's potency. The substitution of an additional carboxylic acid resulted in a 10-fold increase in binding affinity observed for diacid 4. The binding affinities for subsequent compounds were eventually increased 1000-fold over that of the literature leads through a systematic SAR study. Thus the AII receptor binding affinity [IC50 (microM)] of 15 microM for literature lead 1, for example, was increased to 0.018 and 0.012 microM for compounds 33 and 53. A structure affinity relationship has been found requiring the presence of four key elements for good activity: (1) an additional phenyl ring at the N-benzyl para position of the benzylimidazole nucleus, (2) an acidic functionality at the ortho position of the terminal aromatic ring, (3) a lipophilic side chain at the imidazole 2 position of three to five carbon atoms in length, and (4) a group at the imidazole 5-position capable of hydrogen bonding. The synthesis as well as the pharmacological activity of the compounds in this new series of AII receptor antagonists are presented. PMID- 2329554 TI - Nonpeptide angiotensin II receptor antagonists: N-[(benzyloxy)benzyl]imidazoles and related compounds as potent antihypertensives. AB - A series of compounds has been synthesized and demonstrated to be antagonists of the angiotensin II (AII) receptor. These compounds are structurally related to the N-(benzamidobenzyl)imidazoles and extend the scope of this new class of nonpeptide AII antagonists. It has been found that the amide linkage (X = NHCO) in the N-(benzamidobenzyl)imidazoles can be replaced successfully by a variety of groups (X = single bond, O, S, CO, OCH2, CH = CH, NHCONH); linkers of 0-1 atoms in length are most effective. When administered intravenously to awake renal hypertensive rats, these compounds are potent antihypertensives. PMID- 2329555 TI - Fluoronaphthyridines and quinolones as antibacterial agents. 2. Synthesis and structure-activity relationships of new 1-tert-butyl 7-substituted derivatives. AB - A number of 7-substituted-1-tert-butyl-6-fluoroquinolone-3-carboxylic acids and 7 substituted-1-tert-butyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids have been prepared and tested for antibacterial activities. Among those the 7 aminopyrrolidinyl 20b and the 7-diazabicyclo naphthyridine 18b are the most potent compounds in vitro and in vivo. Physicochemical data and acute toxicity are also discussed. Compound 18b, BMY 40062, exhibits the most favorable overall properties, considering in vitro and in vivo microbiological activity, its low toxicity, and pharmacokinetic profile, and was selected for clinical evaluation. PMID- 2329556 TI - Polyamine analogues with antitumor activity. AB - A series of tetraamines derived from 1,8-diaminooctane was prepared and tested as antitumor agents. The reaction of 1,8-diaminooctane with acrylonitrile gave N,N' bis(cyanoethyl)-1,8-diaminooctane, which was reduced to tetraamine 20. Alkylation of the terminal nitrogen atoms of the tetra-Boc derivative of this compound by methyl or ethyl halide followed by removal of the Boc groups gave the bis(alkyl)polyamines 26a and 26b, respectively. These three compounds exhibit promising antitumor activity in the mouse L1210 leukemia model. Coadministration of a polyamine oxidase inhibitor potentiated the antitumor activity. PMID- 2329557 TI - Potential antitumor agents. 60. Relationships between structure and in vivo colon 38 activity for 5-substituted 9-oxoxanthene-4-acetic acids. AB - 9-Oxoxanthene-4-acetic acids are a class of antitumor agents effective against the mouse colon adenocarcinoma 38 in vivo. Within this class, 5-substituents on the xanthenone are known to enhance potency. To extend structure-activity relationships for the class, a series of derivatives bearing a wide variety of substituents at the 5-position have been prepared and evaluated. The results suggest that activity correlates better with the lipophilic properties of substituents rather than with their electronic properties. Generally, lipophilic substituents result in more active compounds, but there may be a size limitation on such substituents. The 5-methyl derivative is the most dose-potent of the analogues studied. PMID- 2329558 TI - Nucleoside conjugates. 11. Synthesis and antitumor activity of 1-beta-D arabinofuranosylcytosine and cytidine conjugates of thioether lipids. AB - Five 1-beta-D-arabinofuranosylcytosine conjugates and two cytidine conjugates of thioether lipids (1-S-alkylthioglycerols) linked by a pyrophosphate diester bond have been prepared and their antitumor activity against an ara-C2 sensitive (L1210/0) and two ara-C resistant L1210 lymphoid leukemia sublines in mice were evaluated. These prodrugs of ara-C include ara-CDP-rac-1-S-hexadecyl-2-O palmitoyl-1-thioglycerol (8a), ara-CDP-rac-1-S-octadecyl-2-O palmitoylthioglycerol (8b), and ara-CDP-rac-1-S-octadecyl-2-O-methyl(or -ethyl, hexadecyl)thioglycerols (8c-e). The cytidine conjugates include CDP-rac-1-S octadecyl-2-O-palmitoyl(or -methyl)- 1-thioglycerols (9a and 9b). Sonicated solutions of the conjugates existed in the form of micellar disks (size 0.01-0.04 microns). Single doses (200-400 mg/kg) of 8a and 8b produced significant increase in life span (257-371%) in mice bearing ip implanted L1210/0 leukemia. In contrast, conjugates 8c-e were less effective (ILS 19-75%) and cytidine conjugates (9a and 9b) were ineffective. Even though 8a and 8b were found to be curative in a high percentage of mice bearing ip implanted partially ara-C resistant L1210 subline [L1210/ara-C(I)], they were completely ineffective against deoxycytidine kinase deficient ara-C resistant L1210 subline [L1210/ara C(II)]. However, the present results, together with the previous, demonstrate that 8a and 8b are promising new prodrugs of ara-C with improved efficacy. PMID- 2329559 TI - Cytotoxicity and antitumor activity of some tetrahedral bis(diphosphino)gold(I) chelates. AB - We report the cytotoxicity toward B16 cells and antitumor activity in three transplantable tumor models of a series of ionic, tetrahedral, bischelated gold diphosphine complexes of the type [Au1(R2PYPR2')2]X, where Y = (CH2)2, (CH2)3, or cis-CH = CH. The anion (X = Cl, Br, I, CH3SO3, NO3, PF6) had little effect upon activity. The R = R' = phenyl complexes 1, 7, and 8 [Y = (CH2)2, (CH2)3, cis-CH = CH, X = Cl] were the most active against P388 leukemia, with an increase in lifespan ranging from 83 to 92% and were also active against M5076 sarcoma and B16 melanoma. Complexes with pyridyl or fluorophenyl substituents had reduced activities. For the latter, 19F and 31P NMR were used to verify the formation of bischelated gold(I) complexes in solution. The reduced activity of the complex with R = Et and R' = Ph and inactivity with R = R' = Et are discussed in terms of their increased reactivity as reducing agents. 31P NMR studies show that [AuI(Et2P(CH2)2PPh2)2]Cl readily reacts with serum, albumin, and Cu2+ ions to give oxidized ligand. PMID- 2329560 TI - Antitumor imidazotetrazines. 20. Preparation of the 8-acid derivative of mitozolomide and its utility in the preparation of active antitumor agents. AB - The preparation of 3-(2-chlorethyl)-4-oxo-3H-imidazo[5,1-d]-1,2,3,5- tetrazine-8 carboxylic acid, a key derivative of mitozolomide in our exploration of the structure-activity relationships of this class of antitumor agents, is described. The facile conversion to the 8-carbonyl chloride gave a derivative that reacted preferentially with nucleophiles at the 8-position rather than at the reactive 4 oxo group, allowing the preparation of a wide range of ester, thioester, amide (including an amide derived from an amino acid), hydroxamic acid, hydrazide and sulfoximide, azide and diazoacetyl derivatives. The in vivo activity is presented of a range of these compounds against TLX5 lymphoma and L1210 leukemia cell lines. PMID- 2329562 TI - Synthesis, pharmacological effects, and conformation of 4,4-disubstituted 1,4 dihydropyridines. AB - 4,4-Disubstituted 1,4-dihydropyridines are synthesized by intramolecular addition of sulfinyl carbanions to pyridines. These disubstituted derivatives show a loss of Ca antagonistic potency of up to three powers of 10 both in vitro on aortic rings and in vivo on anaesthetized dogs as compared to examples that are monosubstituted at the 4-position of the DHP ring. As the X-ray structure shows, the 4-aryl substituent is present not in the accustomed axial conformation, but in an equatorial one. This dramatic change in conformation could be the reason for the major loss of activity and would indicate the need for axial conformation of the aryl residue in pharmacologically active 1,4-dihydropyridines. The change in conformation was also confirmed by quantum chemical calculations (AM1). PMID- 2329561 TI - Synthesis and biological properties of novel phosphotriesters: a new approach to the introduction of biologically active nucleotides into cells. AB - A series of aryl bis(3'-O-acetylthymidin-5'-yl) phosphate derivatives have been synthesized in order to find a suitable aryl derivative which would hydrolyze to the bis(nucleosid-5'-yl) phosphate under physiological conditions. The 4 (methylsulfonyl)phenyl derivative was selected and 4-(methylsulfonyl)phenyl bis[(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl] phosphate (6d) and bis[2-(guanin-9 ylmethoxy)ethoxy]-4-(methylsulfonyl)phenyl phosphate (7b) were prepared. The former compound (6d) was stable in human serum and only following hydrolysis to the 5'-5'-linked diester (half-life of 17 h at pH 7.7) was it enzymatically degraded very rapidly by phosphodiesterases. Compounds 6d and 7b were evaluated for antiherpesvirus effects, both in vitro and in vivo. Their antiviral spectrum and potency was remarkably similar to that of (E)-5-(2-bromovinyl)-2' deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)-methyl]guanine (ACV), suggesting that they only act as prodrugs of BVDU and ACV, respectively. However, compound 6d did show unexpected toxicity, which could be explained by the liberation of BVDUMP following penetration of the triester into the cell. PMID- 2329563 TI - Synthesis and antihyperglycemic activity of novel 5-(naphthalenylsulfonyl)-2,4 thiazolidinediones. AB - A series of 5-(naphthalenylsulfonyl)-2,4-thiazolidinediones were synthesized and evaluated for antihyperglycemic activity in an insulin-resistant, genetically diabetic db/db mouse model of non-insulin-dependent diabetes mellitus (NIDDM). The sulfones could be synthesized by a novel, selective C-5 sulfonylation of dilithio-2,4-thiazolidinedione with appropriate sulfonyl chlorides. Within this series, naphthalene was found to be superior to other groups for eliciting antihyperglycemic activity, including the p-alkoxyphenyl group found in ciglitazone, a prototypical agent for this activity. Attachment of the 5-sulfonyl 2,4-thiazolidinedione moiety to the 2-naphthalene position led to optimum activity. Other linkers between the naphthalene and 2,4-thiazolidinedione rings, such as thio, methylene, oxy, and sulfinyl led to decreased antihyperglycemic activity. The best analogue, 5-(2-naphthalenylsulfonyl)-2,4-thiazolidinedione (AY 31,637) was equipotent to ciglitazone in two animal models of NIDDM. PMID- 2329564 TI - Molecular design, synthesis, and antiinflammatory activity of a series of beta aminoxypropionic acids. AB - Previous experimental and theoretical studies carried out on the mechanism of action of adrenergic drugs have shown that the (methyleneaminoxy)methyl moiety (C = NOCH2, MAOMM) can be considered as a "bioisostere" of an aryl group (Ar). On this basis, a series of substituted beta-aminoxypropionic acids (AOPAs) were synthesized as analogues of antiinflammatory arylacetic acids (ArAAs), in which the Ar portion is substituted by the MAOMM, with the aim of evaluating whether any antiinflammatory activity could be obtained from this class of drugs after the substitution of the Ar with the MAOMM. The antiinflammatory activity of the AOPAs synthesized was determined by carageenan-induced rat paw edema, using diclofenac as the reference drug. The pharmacological data showed that most of the AOPAs examined exhibit a significant antiinflammatory activity, which in the case of the (E)-3-(benzylideneaminoxy)propionic acid (7q) is very close to that of the reference drug. Structural and theoretical studies were carried out in order to compare the conformation and the molecular reactivity of the AOPAs with those of the ArAAs. Pharmacological results showed that the ArAAs also generally exhibit an antiinflammatory activity after the substitution of the Ar with the MAOMM, thus supporting the hypothesis of a bioisosterelike relationship between these two moieties in this class of NSAIDs. PMID- 2329565 TI - Retinobenzoic acids. 5. Retinoidal activities of compounds having a trimethylsilyl or trimethylgermyl group(s) in human promyelocytic leukemia cells HL-60. AB - The retinoidal activities of trimethylsilyl or trimethylgermyl-containing retinobenzoic acids are discussed on the basis of differentiation-inducing activity on human promyelocytic leukemia cells HL-60. Compounds with a trimethylsilyl or trimethylgermyl group at the meta position of the generic formula 2 have more potent activities than the corresponding retinobenzoic acids with a m-tert-butyl group. Compounds having two m-trimethylsilyl or trimethylgermyl groups also have strong activities, and (E)-4-[3-[3,5 bis(trimethylsilyl)phenyl]-3-oxo-1-propenyl]benzoic acid (22, Ch55S) and (E)-4-[3 [3,5-bis(trimethylgermyl)phenyl]-3-oxo-1- propenyl]benzoic acid (35, Ch55G) are more active than retinoic acid by 1 order of magnitude. However, in the para substituted chalcone derivatives, the replacement of a tert-butyl group (49, Ch40) with a trimethylsilyl (27, Ch40S) or a trimethylgermyl (30, Ch40G) group caused the disappearance of the activity. PMID- 2329566 TI - Synthesis, conformation, and immunosuppressive activity of cyclosporines that contain epsilon-oxygen (4R)-4-[(E)-butenyl]-4,N-dimethyl-L-threonine analogues in the 1-position. AB - A series of CsA analogues that contain novel epsilon-oxygen isosteres of (4R)-4 [(E)-butenyl]-4,N-dimethyl-L-threonine (MeBmt) in the 1-position were synthesized. The key steps for the syntheses of enantiomerically pure epsilon oxygen MeBmt analogues 4-7 were based on the stereoselective epoxidation of cis allylic alcohol derivative 12 with a peracid, followed by the application of a base-catalyzed intramolecular rearrangement of epoxyurethane 15, which was derived from the reaction of epoxy alcohol 14 and methyl isocyanate. All epsilon oxygen MeBmt analogues have the same stereochemistry and the same functional groups as those on the alpha,beta,gamma-carbons of MeBmt except for the double bond of MeBmt, which is replaced by the -OCH2-group. The syntheses of the peptide portion of CsA analogues followed the strategy we reported previously. The immunosuppressive activities of CsA analogues 28a-e, determined by inhibition of concanavalin A stimulated thymocytes, showed that 28b, which has the closest structural resemblance to MeBmt, retains about 7-10% of activity of CsA, whereas the analogues 28a, 28c, and 28e retain about 2-5% activity. It is interesting to note that 28d, which has the larger benzyl group on the end of the side chain, is about 20-25% as active as CsA. Extensive conformational analyses by 1D and 2D NMR indicated that the conformation of the 33-membered peptide ring system for all CsA analogues was very similar to that of CsA. However, the NMR analyses revealed that the 1-position side chain of all these CsA analogues adopted a novel conformation in chloroform by forming a different intramolecular hydrogen bond between the beta-OH and the epsilon-oxygen of the same residue. The NMR data also suggest that the chloroform conformation of these CsA analogues is similar to the conformation observed in the crystal structure of CsA in that the 1-position side chain is folded across the cyclic peptide ring system. PMID- 2329567 TI - Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogues. AB - Thirty-eight analogues of 1-phenylcyclohexylamine (PCA), a phencyclidine (PCP) derivative, were examined for their activities in the mouse maximal electroshock (MES) seizure test and in a motor-toxicity assay. In addition, we determined the binding affinities of the compounds for PCP acceptor sites in rat brain membranes labeled with [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine. Many of the analogues were protective against MES seizures (ED50s of 5-41 mg/kg, ip) and all of these compounds caused motor toxicity. The potencies in the motor toxicity and MES seizure tests showed a moderate correlation with the affinities for PCP sites. Several analogues exhibited a greater separation of potencies in the motor toxicity and MES seizure tests than did the parent compound PCA. These were obtained by (i) 3-methylation of the cyclohexyl ring trans to the phenyl ring, (ii) methoxylation at the ortho position on the phenyl ring, and (iii) contraction of the cyclohexane ring to form the corresponding cyclopentane. PMID- 2329568 TI - (Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme. 2. Terminal amino acid analogues of (S)-1-[6-amino-2 [[hydroxy(4 phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline. AB - Analogues of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl] L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and evaluated as inhibitors of angiotensin converting enzyme in vitro and in vivo. In general, the addition of lipophilic substituents to the 4-position of proline of the parent phosphonate 1 resulted in substantial increases in in vitro activity. The largest improvements were observed in the case of cis-benzyl (36-fold) and dithioketal (24-fold) analogues 2r and 2x, respectively. These enhancements of in vitro activity were accompanied by modest increases (2-3.5-fold) in in vivo (iv) activity. Among the various terminal amino acid replacements examined in this study, the indoline-based analogue 2i was by far the most potent compound on iv administration in the normotensive rat. PMID- 2329569 TI - Synthesis and biological activity of some derivatives of rifamycin P. AB - A series of derivatives of rifamycin P, an antibiotic produced by fermentation of a mutant strain of Nocardia mediterranea or by chemical modification of rifamycin S, have been prepared. The structures of these compounds were determined by 1H NMR, IR, UV, and LC/MS. Their in vitro and in vivo antibacterial activities in comparison with rifampicin and two other rifamycins under investigation were evaluated. The derivatives were more active than rifamycin P against Mycobacterium avium complex and other slowly and rapidly growing nontuberculous mycobacteria which frequently cause systemic infection in patients with AIDS. 2' (Diethylamino)rifamycin P (P/DEA) appears suitable for further investigation. PMID- 2329570 TI - Structure-activity relationships for the carboxy-terminus truncated analogues of angiotension II, a new class of angiotensin II antagonists. AB - A series of analogues of the recently reported angiotensin II (AII) antagonist [Sar1]AII-(1-7)-amide or des-Phe8[Sar1]AII (3) have been prepared by solid-phase synthesis and purified by reverse-phase liquid chromatography. The agonist and antagonist properties of these carboxy-truncated analogues of AII were determined in the isolated rabbit aorta assay. In the analogues tested, replacement of aspartic acid in position 1 by sarcosine was found necessary to produce significant antagonist activity. At position 7 of the des-Phe8 analogues, prolinamide could be replaced by proline without significant change in the biological activity. However, substitution of 7-prolinamide by either glycinamide or sarcosinamide provided inactive peptides. Methylation of the 4-tyrosine in [Sar1]AII-(1-7)-NH2 preserved the antagonist potency in isolated rabbit aorta. Deletion of the proline at position 7 resulted in inactive hexapeptides, both in the Asp1 and Sar1 series. However synthesis of the N,N-dimethyl amide at the N terminus afforded hexapeptide [Sar1]AII-(1-6)-N(CH3)2 (10) with a pA2 value of 7.05. All the antagonistic peptides synthesized were fully reversible, competitive antagonists in vitro. These findings indicate that the structural requirements for receptor blockade by these C-truncated analogues are quite stringent with respect to the nature of the amino acid at positions 1 and 6/7. The analogues 2, 3, 7, 10, 11 (saralasin), and 12 (sarmesin) were tested in vivo in the anesthetized rat and were found to inhibit the AII pressor response. In addition, 3 inhibited angiotensin II stimulated aldosterone release from isolated rat adrenal zona glomerulosa cells and had no agonist activity by itself at the doses tested. Interestingly, analogue 3, when injected intracerebroventricularly in conscious rats, failed to antagonize the dipsogenic response to an angiotensin II icv injection and this reflects some heterogeneity in the AII receptor population. Peptide 3 is the first example of an antagonist that discriminates between peripheral and brain receptor subtypes. PMID- 2329571 TI - Studies on hindered phenols and analogues. 2. 1,3-Benzoxathioles having SRS-A inhibiting activity. AB - A series of hindered phenolic 1,3-benzoxathioles (7a-l) were prepared and investigated for biological properties. Many compounds had LPO-lowering, antisuperoxide inhibiting, SRS-A inhibiting, and 5-lipoxygenase inhibiting activities. Among them, 5-hydroxy-4,6,7-trimethyl-2-propyl-1,3-benzoxathiole (7d) and 3-(5-hydroxy-4,6,7-trimethyl-1,3-benzoxathiol-2-yl)propanol (7j) were most potent in SRS-A inhibiting and 5-lipoxygenase inhibiting activities, respectively, and were selected for further development as candidate drugs for the treatment of asthma. PMID- 2329572 TI - Synthesis and biological evaluation of prodrugs of zidovudine. AB - A series of prodrugs of zidovudine (AZT) has been synthesized in an effort to enhance the uptake of the prodrugs by the HIV-1 infected cells and to increase the plasma half-life of AZT. The 5'-OH function of AZT was esterified with various acids in the presence of DCC and 4-(dimethylamino)pyridine (DMAP). The prodrug moieties included (a) morpholine and N-phenylpiperazine-1-acetic acid, (b) 1,4-dihydro-1-methyl-3-nicotinic acid, (c) retinoic acid, and (d) certain amino acids. The anti-HIV-1 activity of the esters was determined in peripheral blood lymphocytes. The IC50 for AZT in this system was 0.12 microM whereas for prodrugs it ranged from 0.05 to 0.2 microM. The prodrugs were generally less cytotoxic than AZT except the retinoic acid ester. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterases with t1/2 ranging from 10 to 240 min. Drug uptake studies in H9 cells with radiolabeled analogues demonstrated that the retinoic acid ester achieved approximately 4-fold higher intracellular concentration than [3H]AZT. However, 1,4-dihydro-1-methyl-3-[(pyridylcarbonyl)oxy] ester (5) was the most active agent of this series and had a higher therapeutic index than AZT. PMID- 2329573 TI - Dihydropyrimidine calcium channel blockers: 2-heterosubstituted 4-aryl-1,4 dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines. AB - 2-Heterosubstituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecar box ylic acid esters 8, which lack the potential CS symmetry of dihydropyridine calcium channel blockers, were prepared and evaluated for biological activity. Biological assays using potassium-depolarized rabbit aorta and radioligand binding techniques showed that some of these compounds are potent mimics of dihydropyridine calcium channel blockers. The combination of a branched ester (e.g. isopropyl, sec-butyl) and an alkylthio group (e.g. SMe) was found to be optimal for biological activity. When compared directly with similarly substituted 2 heteroalkyldihydropyridines 9, dihydropyrimidines 8 were found to be 30-fold less active. The solid-state structure of dihydropyrimidine analogue 8g shows that these compounds can adopt a molecular conformation which is similar to the reported conformation of dihydropyridine calcium channel blockers. PMID- 2329574 TI - Synthesis and antimalarial activity of (+)-deoxoartemisinin. AB - (+)-Deoxoartemisinin (2), a new and more active antimalarial agent, was successfully prepared from artemisinin in one step using NaBH4 and BF3.Et2O in THF. (-)-Deoxodeoxyartemisinin (5), a potential metabolite of deoxoartemisinin, was also prepared either from 2 or from artemisinic acid. 2 shows 8-fold increased antimalarial activity in vitro against chloroquine-resistant malaria as compared to artemisinin (1). Compound 2 possesses superior in vivo antimalarial activity to 1. PMID- 2329575 TI - Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents. AB - The thermal Fischer indolization of hydrazones resulting from 4-hydrazino-5 methyl-1H-pyridin-2-one and various beta- and alpha-tetralones led to 4-methyl 6,7-dihydro-2H,5H-pyrido[4,3- b]benzo[e]indol-1-ones and 4-methyl-11-dihydro 2H,5H-pyrido[4,3- b]benzo[g]indol-1-ones, respectively. After aromatization, these compounds were transformed by phosphorus oxychloride, giving 1-chloro-4 methyl-5H-pyrido[4,3- b]benzo[e]- and -benzo[g]indoles which were substituted by [(dialkylamino)alkyl]amines. The resulting 1-[[(dialkylamino)alkyl]amino]-4 methyl-5H-pyrido- [4,3-b]benzo[e]- and -benzo[g]indoles, as well as hydroxy derivatives obtained by demethylation of methoxylated compounds with hydrobromic acid, were tested for antitumor activity in vitro (leukemic and solid tumor cells) and in vivo on various experimental tumor models using the standard NCI protocols. 1-[[3-(Dialkylamino)propyl]-amino]-4-methyl-9-hydroxy-5H-pyrido[4,3- b]benzo[e]indoles appeared as a promising new class of antineoplastic agents. PMID- 2329576 TI - Crystallization of a proform of aerolysin, a hole-forming toxin from Aeromonas hydrophila. AB - Crystals of proaerolysin, the precursor of the hole-forming toxin from Aeromonas hydrophila, have been obtained. The mature form of this protein binds to a receptor on mammalian cells, aggregates and forms 30 A holes in the membrane. The crystals are tetragonal, space group P4(3)2(1)2, a = b = 104.00 A, c = 222.0 A. They contain a dimer in the asymmetric unit and diffract to a resolution of 2.6 A. PMID- 2329577 TI - Weight matrix descriptions of four eukaryotic RNA polymerase II promoter elements derived from 502 unrelated promoter sequences. AB - Optimized weight matrices defining four major eukaryotic promoter elements, the TATA-box, cap signal, CCAAT-, and GC-box, are presented; they were derived by comparative sequence analysis of 502 unrelated RNA polymerase II promoter regions. The new TATA-box and cap signal descriptions differ in several respects from the only hitherto available base frequency Tables. The CCAAT-box matrix, obtained with no prior assumption but CCAAT being the core of the motif, reflects precisely the sequence specificity of the recently discovered nuclear factor NY I/CP1 but does not include typical recognition sequences of two other purported CCAAT-binding proteins, CTF and CBP. The GC-box description is longer than the previously proposed consensus sequences but is consistent with Sp1 protein-DNA binding data. The notion of a CACCC element distinct from the GC-box seems not to be justified any longer in view of the new weight matrix. Unlike the two fixed distance elements, neither the CCAAT- nor the GC-box occurs at significantly high frequency in the upstream regions of non-vertebrate genes. Preliminary attempts to predict promoters with the aid of the new signal descriptions were unexpectedly successful. The new TATA-box matrix locates eukaryotic transcription initiation sites as reliably as do the best currently available methods to map Escherichia coli promoters. This analysis was made possible by the recently established Eukaryotic Promoter Database (EPD) of the EMBL Nucleotide Sequence Data Library. In order to derive the weight matrices, a novel algorithm has been devised that is generally applicable to sequence motifs positionally correlated with a biologically defined position in the sequences. The signal must be sufficiently over-represented in a particular region relative to the given site, but need not be present in all members of the input sequence collection. The algorithm iteratively redefines the set of putative motif representatives from which a weight matrix is derived, so as to maximize a quantitative measure of local over-representation, an optimization criterion that naturally combines structural and positional constancy. A comprehensive description of the technique is presented in Methods and Data. PMID- 2329578 TI - Sequence and gene organization of the chicken mitochondrial genome. A novel gene order in higher vertebrates. AB - The 16,775 base-pair mitochondrial genome of the white Leghorn chicken has been cloned and sequenced. The avian genome encodes the same set of genes (13 proteins, 2 rRNAs and 22 tRNAs) as do other vertebrate mitochondrial DNAs and is organized in a very similar economical fashion. There are very few intergenic nucleotides and several instances of overlaps between protein or tRNA genes. The protein genes are highly similar to their mammalian and amphibian counterparts and are translated according to the same variant genetic code. Despite these highly conserved features, the chicken mitochondrial genome displays two distinctive characteristics. First, it exhibits a novel gene order, the contiguous tRNA(Glu) and ND6 genes are located immediately adjacent to the displacement loop region of the molecule, just ahead of the contiguous tRNA(Pro), tRNA(Thr) and cytochrome b genes, which border the displacement loop region in other vertebrate mitochondrial genomes. This unusual gene order is conserved among the galliform birds. Second, a light-strand replication origin, equivalent to the conserved sequence found between the tRNA(Cys) and tRNA(Asn) genes in all vertebrate mitochondrial genomes sequenced thus far, is absent in the chicken genome. These observations indicate that galliform mitochondrial genomes departed from their mammalian and amphibian counterparts during the course of evolution of vertebrate species. These unexpected characteristics represent useful markers for investigating phylogenetic relationships at a higher taxonomic level. PMID- 2329579 TI - Plasmid and chromosomal DNA replication and partitioning during the Caulobacter crescentus cell cycle. AB - Cell division in Caulobacter crescentus yields a swarmer and a stalked cell. Only the stalked cell progeny is able to replicate its chromosome, and the swarmer cell progeny must differentiate into a stalked cell before it too can replicate its chromosome. In an effort to understand the mechanisms that limit chromosomal replication to the stalked cell, plasmid DNA synthesis was analyzed during the developmental cell cycle of C. crescentus, and the partitioning of both the plasmids and the chromosomes to the progeny cells was examined. Unlike the chromosome, plasmids from the incompatibility groups Q and P replicated in all C. crescentus cell types. However, all plasmids tested showed a ten- to 20-fold higher replication rate in the stalked cells than the swarmer cells. We observed that all plasmids replicated during the C. crescentus cell cycle with comparable kinetics of DNA synthesis, even though we tested plasmids that encode very different known (and putative) replication proteins. We determined the plasmid copy number in both progeny cell types, and determined that plasmids partitioned equally to the stalked and swarmer cells. We also reexamined chromosome partitioning in a recombination-deficient strain of C. crescentus, and confirmed an earlier report that chromosomes partition to the progeny stalked and swarmer cells in a random manner that does not discriminate between old and new DNA strands. PMID- 2329580 TI - Refinement of the influenza virus hemagglutinin by simulated annealing. AB - We have applied the method of simulated annealing to the refinement of the 3 A resolution crystal structure of the influenza virus hemagglutinin glycoprotein, using the program X-PLOR. Two different methods were introduced into X-PLOR to treat the non-crystallographic symmetry present in this and in other crystal structures. In the first, only the unique protomer atoms are refined; by application of the non-crystallographic symmetry operators to the protomer atoms, the X-ray structure factor derivatives are effectively averaged, and a non-bonded energy term models the interactions of the protomer with its neighbors in the oligomer without explicit refinement of the other protomers in the crystallographic asymmetric unit. In the second method, the entire asymmetric unit is refined, but an effective energy term is added to the empirical energy that restrains symmetry-related atomic positions to their average values after least-squares superposition. Several other modifications and additions were made to previously published X-PLOR protocols, including weighting of the X-ray terms, maintenance of the temperature of the molecular dynamics simulation, treatment of charged groups, changes in the values of certain empirical energy parameters, and the use of N-linked carbohydrate empirical energy parameters. The hemagglutinin refinement proceeded in several stages. An initial round of simulated annealing of the monomer was followed by rigid-body refinement of the 3-fold non crystallographic symmetry axis position and a second round of monomer refinement. A third round was performed on the trimer using non-crystallographic symmetry restraints in all regions except those in lattice contacts showing obvious derivations from 3-fold symmetry. The refinement was completed with several rounds of conventional positional and isotropic temperature factor refinement needed to correct bad model geometry introduced by high-temperature molecular dynamics in regions of weak electron density. This structure was then used as the basis for refinement of three crystallographically isomorphous hemagglutinin structures, including complexes with the influenza virus receptor, sialic acid. Model geometry comparable to well-refined high-resolution structures was obtained with relatively little manual intervention, demonstrating the ability of simulated annealing refinement to produce highly idealized structures at moderate resolution. PMID- 2329581 TI - Studies of crystal growth mechanisms of proteins by electron microscopy. AB - We have used electron microscopy to examine the surfaces of lysozyme crystals and deduce mechanisms of crystal growth. We find that growth occurs by a lattice defect mechanism at low supersaturation and by two-dimensional nucleation at high supersaturation. Step velocities and two-dimensional nucleation rates are obtained, and their dependence on supersaturation is compared with theory. Some features of the observed surface structure can be related to the specific topology and strengths of the bonds in the P4(3)2(1)2 lattice. Preliminary results on the early stages of nucleation and the phenomenon of cessation of growth are presented. PMID- 2329582 TI - Characterization of microtubule protofilament numbers. How does the surface lattice accommodate? AB - Frozen-hydrated specimens of microtubules assembled in vitro were observed by cryoelectron microscopy. Specimens were of both pure tubulin, and of microtubule protein isolated by three cycles of assembly and disassembly. It is shown that the characteristic image contrast of individual microtubules allows the microtubule protofilament number to be determined unambiguously. Microtubules with 13, 14 and 15 protofilaments are observed to coexist in specimens prepared under various assembly conditions. Confirmation of these results is obtained by observations of thin sections of pelleted samples fixed and stained using the glutaraldehyde/tannic acid technique. Images of individual microtubules show both characteristic contrast profiles across their width and typical variations of these profiles along their length. The profiles across the images indicate the protofilament number of the microtubule. The lengthwise variations indicate how the protofilaments are aligned with respect to the microtubule axis giving what has previously been called a supertwist. In 13 protofilament microtubules the protofilaments are paraxial. In 14 and 15 protofilament microtubules, the protofilaments are skewed with respect to the microtubule axis. The skew is greater for the 15 protofilament case than for 14 protofilaments. The skew allows the extra protofilaments to be accommodated by the surface lattice. These results should also be relevant to situations in vivo. PMID- 2329583 TI - Dynamic Monte Carlo simulations of globular protein folding/unfolding pathways. I. Six-member, Greek key beta-barrel proteins. AB - In the context of a simplified diamond lattice model of a six-member, Greek key beta-barrel protein that is closely related in topology to plastocyanin, the nature of the folding and unfolding pathways have been investigated using dynamic Monte Carlo techniques. The mechanism of Greek key assembly is best described as punctuated "on site construction". Folding typically starts at or near a beta turn, and then the beta-strands sequentially form by using existing folded structure as a scaffold onto which subsequent tertiary structure assembles. On average, beta-strands tend to zip up from one tight bend to the next. After the four-member, beta-barrel assembles, there is a long pause as the random coil portion of the chain containing the long loop thrahes about trying to find the native state. Thus, there is an entropic barrier that must be surmounted. However, while a given piece of the protein may be folding, another section may be unfolding. A competition therefore exists to assemble a fairly stable intermediate before it dissolves. Folding may initiate at any of the tight turns, but the turn closer to the N terminus seems to be preferred due to well-known excluded volume effects. When the protein first starts to fold, there are a multiplicity of folding pathways, but the number of options is reduced as the system gets closer to the native state. In the early stages, the excluded volume effect exerted by the already assembled protein helps subsequent assembly. Then, near the native conformation, the folded parts reduce the accessible conformational space available to the remaining unfolded sections. Unfolding essentially occurs in reverse. Employing a simple statistical mechanical theory, the configurational free energy along the reaction co-ordinate for this model has been constructed. The free energy surface, in agreement with the simulations, provides the following predictions. The transition state is quite near the native state, and consists of five of the six beta-strands being fully assembled, with the remaining long loop plus sixth beta-strand in place, but only partially assembled. It is separated from the beta-barrel intermediate by a free energy barrier of mainly entropic origin and from the native state by a barrier that is primarily energetic in origin. The latter feature is in agreement with the "Cardboard Box" model described by Goldenberg and Creighton but, unlike their model, the transition state is not a high-energy distorted form of the native state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329584 TI - Dynamic Monte Carlo simulations of globular protein folding/unfolding pathways. II. Alpha-helical motifs. AB - Dynamic Monte Carlo simulations of the folding pathways of alpha-helical protein motifs have been undertaken in the context of a diamond lattice model of globular proteins. The first question addressed in the nature of the assembly process of an alpha-helical hairpin. While the hairpin could, in principle, be formed via the diffusion-collision-adhesion of isolated performed helices, this is not the dominant mechanism of assembly found in the simulations. Rather, the helices that form native hairpins are constructed on-site, with folding initiating at or near the turn in almost all cases. Next, the folding/unfolding pathways of four-helix bundles having tight bends and one and two long loops in the native state are explored. Once again, an on-site construction mechanism of folding obtains, with a hairpin forming first, followed by the formation of a three-helix bundle, and finally the fourth helix of the native bundle assembles. Unfolding is essentially the reverse of folding. A simplified analytic theory is developed that reproduces the equilibrium folding transitions obtained from the simulations remarkably well and, for the dominant folding pathway, correctly identifies the intermediates seen in the simulations. The analytic theory provides the free energy along the reaction co-ordinate and identifies the transition state for all three motifs as being quite close to the native state, with three of the four helices assembled, and approximately one turn of the fourth helix in place. The transition state is separated from the native conformation by a free-energy barrier of mainly energetic origin and from the denatured state by a barrier of mainly entropic origin. The general features of the folding pathway seen in all variants of the model four-helix bundles are similar to those observed in the folding of beta barrel, Greek key proteins; this suggests that many of the qualitative aspects of folding are invariant to the particular native state topology and secondary structure. PMID- 2329585 TI - Molecular structure of flavocytochrome b2 at 2.4 A resolution. AB - The crystal structure of flavocytochrome b2 has been solved at 3.0 A resolution by the method of multiple isomorphous replacement with anomalous scattering. Area detector data from native and two heavy-atom derivative crystals were used. The phases were refined by the B.C. Wang phase-filtering procedure utilizing the 67% (v/v) solvent content of the crystals. A molecular model was built first on a minimap and then on computer graphics from a combination of maps both averaged and not averaged about the molecular symmetry axis. The structure was extended to 2.4 A resolution using film data recorded at a synchrotron and refined by the Hendrickson-Konnert procedure. The molecule, a tetramer of Mr 230,000, is located on a crystallographic 2-fold axis and possesses local 4-fold symmetry. Each subunit is composed of two domains, one binding a heme and the other an FMN prosthetic group. In subunit 1, both the cystochrome and the flavin-binding domain are visible in the electron density map. In subunit 2 the cytochrome domain is disordered. However, in the latter, a molecule of pyruvate, the product of the enzymatic reaction, is bound at the active site. The cytochrome domain consists of residues 1 to 99 and is folded in a fashion similar to the homologous soluble fragment of cytochrome b5. The flavin binding domain contains a parallel beta 8 alpha 8 barrel structure and is composed of residues 100 to 486. The remaining 25 residues form a tail that wraps around the molecular 4-fold axis and is in contact with each remaining subunit. The FMN moiety, which is located at the C-terminal end of the central beta-barrel, is mostly sequestered from solvent; it forms hydrogen bond interactions with main- and side-chain atoms from six of the eight beta-strands. The interaction of Lys349 with atoms N-1 and O-2 of the flavin ring is probably responsible for stabilization of the anionic form of the flavin semiquinone and hydroquinone and enhancing the reactivity of atom N 5 toward sulfite. The binding of pyruvate at the active site in subunit 2 is stabilized by interaction of its carboxylate group with the side-chain atoms of Arg376 and Tyr143. Residues His373 and Tyr254 interact with the keto-oxygen atom and are involved in catalysis. In contrast, four water molecules occupy the substrate-binding site in subunit 1 and Tyr143 forms a hydrogen bond to the ordered heme propionate group. Otherwise the two flavin-binding domains are identical within experimental error.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2329586 TI - Contralateral pleural effusion secondary to nonmetastatic renal cell carcinoma. AB - We report a case of contralateral pleural effusion secondary to nonmetastatic renal cell carcinoma that resolved and did not recur after radical nephrectomy. Such effusions are not a contraindication to definitive therapy of the primary renal tumor. PMID- 2329587 TI - Cystotomy, temporary urinary diversion and bladder packing in the management of severe cyclophosphamide-induced hemorrhagic cystitis. AB - Severe hemorrhage from cyclophosphamide-induced cystitis sometimes requires aggressive open management when conventional endoscopic and intravesical therapies have failed. We present 2 patients with intractable hematuria who were managed by open cystotomy, temporary urinary diversion via external ureteral stents, and continuous postoperative bladder packing with gauze and hemostatic agents. Both patients had a dramatic improvement in the hematuria immediately postoperatively and 1 with prolonged followup has no urological disability. We suggest that this procedure be considered for management of severe hemorrhagic cystitis as an alternative to more aggressive surgical therapies, such as formal urinary diversion with cystectomy. PMID- 2329588 TI - Pelvic sarcoma causing gynecomastia. PMID- 2329589 TI - Plasmacytoma of the urethra treated with transurethral resection and radiotherapy. AB - Plasmacytoma, which is a localized malignant plasma cell tumor, occurs rarely and is found mostly in the upper airways of older patients. Two urethral plasmacytomas have been reported, 1 of which was a primary lesion. We describe a primary plasmacytoma of the urethra in a 23-year-old woman who had been exposed to diethylstilbestrol in utero. The patient underwent transurethral resection of the tumor and radiation therapy and has been free of disease for more than 10 years. PMID- 2329590 TI - Seminoma associated with crossed fused renal ectopia. AB - We report a case of seminoma associated with crossed fused renal ectopia and a duplicated vena cava. The impact of these congenital anomalies on the treatment of testicular seminoma is discussed. PMID- 2329591 TI - Bowel injury as a result of penetrating scrotal trauma: review of associated injuries. AB - We report a case of bowel injury as a result of an isolated gunshot wound to the scrotum. Our experience with penetrating scrotal trauma reveals a high rate of associated injuries, the most common being trauma to the soft tissue of the thigh. Our case emphasizes the importance of a thorough preoperative and operative evaluation of patients with penetrating scrotal trauma. PMID- 2329592 TI - On the reversibility of functional bladder changes induced by infravesical outflow obstruction in the rat. AB - Rats were subjected to infravesical outflow obstruction for six weeks. The bladder function was followed by cytometrical and in vitro investigations and by recordings of micturition pattern before and after removal of the obstruction. Cytometrical investigations showed that outflow obstruction for six weeks induced a bladder instability. Further, in the presence of obstruction the micturition pressure was large as was the bladder capacity and the rats had residual urine. After removal of the obstruction the bladder function rapidly normalized. The bladder instability disappeared within one week, bladder capacity decreased as did the micturition pressure. Moreover, only a minor amount of residual urine was present post-obstruction. In vitro investigation showed that the response to carbachol and to electrical stimulation was similar in normal and obstructed bladders. However, after removal of the obstruction a supersensitivity to carbachol as well as to electrical stimulation had developed. Obstructed bladders showed a markedly decreased response to substance P. The sensitivity to substance P was rapidly enhanced post-obstruction and after four days the response was restored to the control level. The present study shows that the bladder function in rats with infravesical outflow obstruction rapidly normalized after removal of the obstruction. The disappearance of the bladder instability despite the developed supersensitivity to muscarinic receptor stimulation supports the opinion that the bladder instability is not of muscarinic origin. PMID- 2329593 TI - Effects of streptozotocin-induced diabetes on bladder function in the rat. AB - Streptozotocin-induced (STZ, 60 mg./kg. I.V.) diabetic male rats underwent cystometrographic (CMG) and electrophysiologic evaluations under urethane anesthesia (1.2 gm./kg.) to determine whether the neural pathways to the urinary bladder are altered in these animals. Diabetic rats (n = 6) in comparison to controls (n = 8) had significantly greater micturition volumes (3.0 +/- 0.8 ml. vs. 0.7 +/- 0.4 ml., p less than 0.001), bladder compliances (0.51 +/- 0.15 cm. H2O/ml. vs. 0.12 +/- 0.09 cm. H2O/ml., p less than 0.001) and bladder weights (225.2 +/- 21.4 mg. vs. 112.2 +/- 18.0 mg., p less than 0.01). No differences were noted in: 1) the thresholds or conduction velocities of axons in the bladder postganglionic nerves, 2) transmission in the major ganglion or 3) the latencies for firing in the supraspinal parasympathetic reflex pathway to the bladder. However, the supraspinal reflex, which was facilitated by bladder distension in 38% of control rats, was not facilitated in any diabetic rats. Another apparent difference in diabetic rats was the absence of spinal reflex response which was noted in 38% of control animals. This study confirmed that CMG changes in STZ induced diabetic rats are similar to those observed clinically in patients with diabetic autonomic neuropathy, and in addition raise the possibility that these changes are produced by a defect in autonomic reflexes. It is also clear that alterations of the micturition reflex pathway in diabetic rats are distinct from those associated with another type of enlarged, abnormal bladder induced by bladder outlet obstruction. PMID- 2329594 TI - Assessment of human genitourinary tumors and chemosensitivity testing in 3 dimensional collagen gel culture. AB - A recently described collagen gel culture technique has been modified to evaluate the growth characteristics and chemosensitivity patterns of genitourinary neoplasms. Fresh human surgical explants incorporated radiolabeled DNA precursors [H3)thymidine or deoxyuridine) in 97% of 38 patient specimens (18/19 bladder, 3/3 prostate, 2/2 testis, 13/14 renal), after being maintained for three to 13 weeks/passage, with several specimens reaching their sixth passage (20 months). Control cellular DNA incorporation ranged from five to 90% (#cells labeled/#cells evaluated), with median labeling for bladder 30%, prostate 80%, testis 90%, and renal 80%. Original histopathologic classification was maintained in all cases. Tumor volume and glucose consumption were other measurable parameters. Seventy three surgical specimen cultures were treated with chemotherapeutic agents after a minimum of four weeks in culture. Single agent exposures were 24 hours at 1X and 10X reported peak plasma concentrations. Combination agents were sequenced as in current clinical protocol for bladder tumors and fourteen day continuous fluorodeoxyuridine (FdURD) exposure for renal tumors. Sensitivity was found in 1/2 prostate and 1/10 renal tumors to Adriamycin, 8/15 bladder and 1/2 testis tumors to cisplatin, 11/28 renal tumors to FdURD and 6/16 bladder tumors to MVAC combination chemotherapy. This culture system offers the advantages of in vivo like solid tumor growth, a high culture success rate, longevity in culture, maintenance of the primary histopathology and reproducible chemosensitivity response. PMID- 2329595 TI - Effects of hypothermia on testicular ischemia. AB - The ischemic effects of prolonged testicular torsion have been well documented; however, prevention or arrest of the damaging effects of prolonged ischemia has been incompletely studied. Two groups of Sprague-Dawley rats were subjected to varying lengths of bilateral testicular ischemia. Group I underwent normothermic ischemia for two, four, and six hours. Likewise, Group II underwent similar time periods of ischemia, however, after thirty minutes of normothermic ischemia the scrotum of each animal was placed into an ice bath maintained at 4C. Two weeks postoperatively, bilateral orchiectomy was performed. Histology of the testes of the two groups was compared. Neither group revealed significant destruction of the germinal epithelium after two hours of ischemia. Group I revealed only 25% preservation of the germinal epithelium at four hours and only 8% preservation at six hours of ischemia. In contrast, Group II which received ice showed 90% preservation of germinal epithelium at four hours and 85% preservation at six hours of ischemia. We conclude that external ice application significantly preserves seminiferous tubules at four and six hours of ischemic injury in the rat testicle. PMID- 2329596 TI - The effect of verapamil on a multi-drug resistant bladder carcinoma cell line and its potential as an intravesical chemotherapeutic agent. AB - A human bladder transitional cell carcinoma cell line, MGH-U1R, exhibits reproducible resistance to doxorubicin. We examined the effects on survival of this cell line caused by verapamil, which has been shown to reverse multi-drug resistance in vitro in other neoplastic cell lines. Both MGH-U1R and MGH-U1, the non-resistant parent cell line, were treated with varying concentrations of doxorubicin alone, verapamil alone, or both drugs simultaneously, all for one hour. Cells were then grown in drug-free medium for 10 days, stained, and counted. Standard survival curves were calculated. Verapamil alone had no significant cytotoxicity. Verapamil at concentrations of 16 micrograms./ml. and 32 micrograms./ml. decreased the IC50 of doxorubicin for MGH-U1R by a factor of 2.5. Using H3-verapamil, we also examined the systemic and local absorption of this drug resulting from intravesical verapamil administration in rabbits. All animals were treated for one hour, and multiple serum samples were drawn during treatment. Verapamil was found in high concentrations in the mucosa, less in the adventitia, and was absent in venous blood. Verapamil effectively reverses resistance to doxorubicin of MGH-U1R in vitro. The intravesical use of verapamil appears to be safe, and may prove to be a useful adjunct in the intravesical therapy of some bladder tumors. PMID- 2329597 TI - The effect of decreasing the concentration of urinary urate on the crystallization of calcium oxalate in undiluted human urine. AB - The effect of lowering the urate concentration, using uricase immobilized on to nylon tubing, on the nucleation, growth and aggregation of calcium oxalate crystals in undiluted human urine was examined. The median urate concentration was significantly (p less than 0.01) reduced from 2.8 to 0.55 mmol/l., but this had no reproducible effect on the metastable limits, the volume of crystalline calcium oxalate deposited and the size of the crystals and aggregates produced from the 10 urine samples examined. It was concluded that further studies aimed at testing the effects of a raised urinary urate concentration on the crystallization of calcium oxalate should be made a matter of high priority. PMID- 2329598 TI - A controlled study of the argon beam coagulator for partial nephrectomy. AB - An argon beam coagulator was evaluated in 25 canine partial nephrectomies to determine its hemostatic capabilities, safety and degree of thermal injury to renal parenchyma. Comparison was made with a control group of seven partial nephrectomies performed by standard technique. In both groups the procedure was performed without renal cooling or clamping of the renal artery. The argon beam coagulator was operated with a power output of 130 watts. Mean operative time for partial nephrectomy was 22 minutes in the control group versus 10 minutes when the argon coagulator was used (p less than 0.001). Mean blood loss was 276 cc by standard technique but only 135 cc with the argon coagulator (p less than 0.001). A regular eschar with a mean depth of tissue necrosis of 2.4 mm. was observed with the argon coagulator. PMID- 2329599 TI - Multimodality treatment of complex renal calculi. AB - More than 2,500 patients were treated for urolithiasis from 1984 to 1987. In an effort to define the relative role of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy with respect to size, location and composition of the calculus 912 of these patients (224 of whom underwent percutaneous nephrolithotomy and 688 of whom underwent extracorporeal shock wave lithotripsy) were reviewed. Size proved to be the only significant factor in the success and complication rates of extracorporeal shock wave lithotripsy but it did not affect the outcome of percutaneous nephrolithotomy. The roles of these 2 modalities were then examined with respect to the treatment of complex renal calculi. We reviewed 376 patients with complex renal calculi, including 40 percutaneous nephrolithotomy patients from the initial 912 patients studied. The initial therapy in 100 of these patients, treated consecutively, was extracorporeal shock wave lithotripsy. The remaining 276 patients were treated by percutaneous nephrolithotomy. The success rate of extracorporeal shock wave lithotripsy monotherapy in the treatment of complex renal calculi was 36%. The success rate of primary percutaneous nephrolithotomy was 83%. We conclude that percutaneous nephrolithotomy should be the primary therapy for patients with complex renal calculi. Extracorporeal shock wave lithotripsy is the preferred treatment for patients with smaller calculi and as an adjunct to percutaneous nephrolithotomy. PMID- 2329600 TI - Treatment of pacemaker patients with extracorporeal shock wave lithotripsy: experience from 2 continents. AB - Patients with cardiac pacemakers currently are treated by extracorporeal shock wave lithotripsy only by agreement between individual physicians and patients. We present the results of a survey of patterns of extracorporeal shock wave lithotripsy treatment (or nontreatment) of patients with pacemakers in the United States and Europe. Letters of inquiry regarding treatment of pacemaker patients were sent to 141 United States extracorporeal shock wave lithotripsy sites and 55 sites in Europe. Responses were received from 81 (57%) and 17 (31%) sites, respectively. A total of 131 patients received 142 treatments and pacemaker related complications occurred in 4 (none was lethal, 3 were minor and all were corrected immediately). No patient required replacement of the pacemaker. No correlation existed between complications and pacemaker type or manufacturer. Urologists who treat patients with a pacemaker required previous clearance of the patients by the cardiologist, a cardiologist in or near the extracorporeal shock wave lithotripsy suite and standby of corrective equipment or temporary pacemakers. PMID- 2329601 TI - Ten years of training community urologists and general surgeons to do cadaver kidney retrievals. AB - We trained 82 community hospital cadaver kidney retrieval teams during a 10-year period ending June 30, 1987. During the last 5 years of that period the concept of multiple organ retrieval was introduced into the training sessions and 429 cadaver kidney grafts were retrieved. Of those kidneys 292 were transplanted at our hospital, and the function of 220 cadaver kidney grafts retrieved by the community hospital teams was compared to that of 72 retrieved by the transplant center retrieval team. Of the cadaver kidney transplants 114 were from multiple organ donors. There was no significant difference in 1-month serum creatinine nadir of surviving grafts (2.1 +/- 1.8 versus 1.9 +/- 1.7 mg. per dl.), 6-month serum creatinine level (1.7 +/- 0.8 versus 1.6 +/- 0.6 mg. per dl.), 12-month serum creatinine level (1.8 +/- 0.9 versus 1.6 +/- 0.6 mg. per dl.) and 5-year actuarial graft survival (44.8 +/- 4.1 versus 52.4 +/- 7.5%), with the community hospital data presented first. The delayed graft function rate was significantly higher in the recipients of cadaver kidney grafts retrieved by community hospital teams (54 versus 35%), which was reduced by the in situ flush technique. There was no significant difference in delayed graft function rate (48 versus 40%) for the 114 cadaver kidney transplants retrieved from multiple organ donors by either community hospital or transplant center teams. With continuing education and quality control, community hospital retrieval teams can provide kidneys satisfactory for transplantation, even when working with multiple organ retrieval teams. PMID- 2329602 TI - Comparison of 2-drug and 3-drug immunosuppression for cadaveric renal transplantation. AB - We compare the results in recipients of cadaveric renal allografts immunosuppressed with cyclosporine and prednisone to those who received immunosuppression with cyclosporine, azathioprine and prednisone. The 2 groups were compared relative to HLA-ABDR matching, plasma reactive antibodies, cold ischemia time, diabetes as a cause of renal failure and recipient age greater than 50 years. The incidences of clinical allograft rejection and grafts lost to rejection were not significantly different in these 2 groups evaluated at 1 year. In the 2-drug immunosuppressed group the actual 3, 6 and 12-month graft function was 87, 86 and 85%, respectively, compared to 79, 78 and 74%, respectively, in the 3-drug immunosuppressed group. A difference in graft survival was due to graft loss secondary to vascular thrombosis and patient death, and not to immunological events. No advantage was demonstrated for the use of 3-drug immunosuppression for kidney allografts over a 2-drug protocol of cyclosporine and prednisone. PMID- 2329603 TI - The case for a percutaneous approach to transitional cell carcinoma of the renal pelvis. AB - Percutaneous treatment of transitional cell carcinoma of the renal pelvis in 4 patients is reported. The presenting symptom was hematuria in 2 patients, while in 2 diagnosis was made by chance at excretory urography. Endoscopic removal of the tumor was not possible in the 2 patients who underwent transurethral ureteroscopy due to the location of the lesion. Percutaneous electroresection of the tumor was performed after puncture of an inferior (3 patients) or middle (1) calix and dilation of the nephrostomy tract up to 30F. Pathological findings revealed a grade 1 papillary carcinoma in 3 patients and a well differentiated inverted papilloma in 1. A single-J ureteral catheter was left in place after the procedure. Cytological, radiographic and endoscopic studies were negative 11, 13, 18 and 24 months after the treatment, respectively. We believe that the percutaneous approach is a feasible option in cases of small, single, low grade lesions not removable via ureteroscopy, particularly in patients at high surgical risk. PMID- 2329604 TI - Clean intermittent self-catheterization: a 12-year followup. AB - We studied retrospectively 75 patients who performed clean intermittent self catheterization for a mean of 7 years (maximum 12 years). Most of the patients had neuropathic bladder dysfunction and 92% were continent. Chronic or recurrent urinary tract infections were present in 42% of the patients. Although the upper urinary tract was well preserved in the majority of the patients regular screening for silent hydronephrosis and/or asymptomatic reflux proved to be necessary. Complications occurred in 15 patients, with a urethral pathological condition being the most frequent complication in our male patients during followup. PMID- 2329605 TI - Flow cytometric analysis of primary and metastatic bladder cancer. AB - A total of 22 patients with high grade P2-4N+ transitional cell carcinoma of the bladder underwent flow cytometric analysis of nuclei obtained from paraffin embedded specimens from the primary (bladder) and metastatic (lymph node) sites. Tumor heterogeneity was defined as polyclonal aneuploidy of the primary tumor (not identified in the population studied) or as a difference in the deoxyribonucleic acid index of the primary and metastatic sites of 0.20 or more (8 patients). With these criteria 8 patients (36%) had heterogeneous tumors and 14 (64%) had homogeneous tumors. The median survival of 14 patients with aneuploid and 8 with diploid primary tumors was 17.5 and 8.0 months, respectively (p equals 0.08, Lee-Desu test). When patient survival was compared to the ploidy of the metastatic site, or in patients with diploid primary and metastatic lesions versus deoxyribonucleic acid aneuploidy at either the primary and/or metastatic site, the aneuploid tumors had a longer survival but this difference was not significant (p equals 0.13 and 0.23, respectively). Our study demonstrates the value of flow cytometry to identify primary metastatic tumor heterogeneity. It also suggests that the presence of metastasis may be a more important factor to define the biological potential of transitional cell carcinoma than is deoxyribonucleic acid ploidy. PMID- 2329606 TI - Surgical management of long urethral strictures. AB - A total of 25 patients with a long urethral stricture involving the bulbomembranoprostatic urethra underwent excision of the afflicted region via the perineal approach with end-to-end anastomosis. Liberation of the distal urethra provided sufficient length for anastomosis without tension of the healthy urethra. Satisfactory results were obtained in 23 of the 25 patients without any functional disturbance of sphincter control. PMID- 2329607 TI - Clinical and molecular evaluation of acetowhite genital lesions in men. AB - A total of 108 male partners of women with cervical condyloma and/or dysplasia underwent evaluation for gross and subclinical condyloma via acetic acid screening with a magnified examination. Biopsies of acetowhite genital skin were obtained for histological and deoxyribonucleic acid hybridization analysis. Of the men 52 (49%) had acetowhite lesions and underwent biopsies, 44 of which were evaluable by histological and deoxyribonucleic acid analyses. Of the lesions 12 had features of condyloma or penile intra-epithelial neoplasia, among which 7 (58%) contained human papillomavirus deoxyribonucleic acid. The remaining 32 lesions revealed minimal histological changes sometimes suggesting condyloma. However, only 5 of the 32 biopsies (16%) contained human papillomavirus deoxyribonucleic acid. A tendency to overdiagnose condyloma based on histological findings is suggested. Criteria by which to identify best human papillomavirus related morphology are presented. Acetowhite genital epithelia with minor (nonspecific) histological changes correlate poorly with human papillomavirus nucleic acids and in most cases do not represent disease involving common viral types. The application of appropriate histological criteria appears to be particularly relevant to management strategies that avoid overtreatment of minor epithelial abnormalities. It remains unclear whether acetowhite genital epithelia positive for human papillomavirus require treatment given the high tendency for recurrence and lack of demonstrated effect on the natural history of cervical carcinoma. PMID- 2329608 TI - Priapism: simple method to prevent retumescence following initial decompression. AB - With recent escalation in the use of vasoactive intracorporeal injections to produce erection, the precise treatment of priapism has again achieved much attention. In particular, high inflow priapism must be managed rapidly and definitively to reestablish equilibrium with venous outflow. However, once penile decompression has been achieved tumescence of the penis can recur if appropriate measures are not taken. This may result in additional penile manipulation and operations leading to an increased risk of impotence. A simple method is presented to prevent recurrent tumescence after initial treatment of priapism, irrespective of the etiology. PMID- 2329609 TI - Analysis and management of chronic testicular pain. AB - A total of 45 patients was seen in consultation between May 1980 and April 1989 for chronic unilateral or bilateral orchialgia, defined as intermittent or constant testicular pain 3 months or longer in duration that significantly interferes with the daily activities of the patient so as to prompt him to seek medical attention. We analyzed 34 patients available for followup in terms of socioeconomic parameters, etiology and duration of pain, associated urological symptomatology, specific treatment and results of therapy. Of the patients 31 underwent surgical treatment after failing medical management (24 orchiectomies, 10 epididymectomies, 5 orchiopexies and 1 hydrocelectomy). Of 10 patients who underwent epididymectomy 9 underwent subsequent orchiectomy as definitive treatment. Of 15 patients who underwent inguinal orchiectomy 11 (73%) reported complete relief of pain, while 4 had partial relief. Of the 9 patients who underwent scrotal orchiectomy 5 (55%) reported complete relief of pain, 3 had partial relief and 1 denied improvement. On the basis of these results we recommend inguinal orchiectomy as the procedure of choice for the management of chronic testicular pain when conservative measures are unsuccessful. PMID- 2329610 TI - Sclerotherapy for hydroceles. AB - Sclerotherapy with 3% sodium tetradecyl sulfate and 3.5% rolitetracycline on an outpatient basis was applied to 55 hydroceles. The over-all cure rate was 96% with an average followup of 13 months. Of the patients 64% were cured after only 1 sclerosant instillation. A post-sclerotherapy operation was necessary in 4% of the patients. Pain of a significant degree occurred after sclerotherapy in only 29% of the patients. Sclerotherapy appears to be an effective, economical and safe form of outpatient therapy for hydroceles. PMID- 2329611 TI - Ureteral obstruction associated with prostate cancer: the outcome after percutaneous nephrostomy. AB - We retrospectively reviewed the outcome of 37 prostate cancer patients with ureteral obstruction treated by percutaneous nephrostomy. The over-all survival was 57% at 1 year and 29% at 2 years (median survival time 21 months). The 1 and 2-year survival rates of 15 patients with no prior hormonal therapy were 73 and 47%, respectively, while those of patients who had previously received hormonal therapy were 48 and 19%, respectively. Median survival times of these groups were 24 months and 12 months, respectively. Of 12 patients who had severe renal failure before percutaneous nephrostomy (serum creatinine greater than or equal to 6.9 mg. per dl.) 9 had an adequate return of renal function (serum creatinine less than 3 mg. per dl.) after drainage and 58% survived more than 1 year (median survival time 22 months). Percutaneous nephrostomy is safe and effective in relieving ureteral obstruction and reasonable survival can be achieved even in patients with renal failure. Percutaneous nephrostomy should be considered strongly in these patients. PMID- 2329612 TI - Bacteriology of upper urinary tract stones. AB - Extensive cultures of stones and urine were performed in 215 patients who underwent an operation for upper urinary tract calculi. Microorganisms could be cultured from the stone in 1 of every 3 patients. Despite the extended culture technique urease-producing microorganisms could be cultured from the stone in only 48% of the patients with calculi that contained magnesium ammonium phosphate. This finding suggests that an infection with urease-producing microorganisms is not obligatory for the formation of this type of stone. Of the patients with calcium oxalate phosphate stones 32% had positive stone cultures, which distinguished them from patients with pure calcium oxalate stones, only 8% of whom had a positive stone culture (p less than 0.001). PMID- 2329613 TI - The mechanisms of continence in the Indiana pouch: a video-urodynamic study. AB - The ileocecal reservoir (Indiana pouch) is a large volume, low pressure continent reservoir well suited for urinary diversion. The mechanism of continence is believed to be the result of several factors, including the natural ileocecal valve resistance, resistance produced by the plication of the ileal segment and normal peristalsis of the ileum. We report the results of a video-urodynamic study in patients with an Indiana pouch, aimed at establishing the factors that contribute to continence and their relative significance. Video-urodynamic studies clearly demonstrate that continence in this type of urinary reservoir is dependent upon a synergism of the aforementioned factors in combination with the low intraluminal pressure of the detubularized bowel. Video-urodynamic studies offer an objective demonstration of the reservoir dynamics and its continence mechanisms, and provide an insight into the possible etiology of incontinence. Such studies also offer an objective means for critical comparison of the different continent urinary reservoirs. PMID- 2329614 TI - Pathophysiology of urinary incontinence after radical prostatectomy. AB - To define the origin of urinary incontinence after radical prostatectomy urodynamic studies in 24 incontinent patients were compared to those of 13 continent patients. A statistically significant difference between incontinent and continent patients was found for the mean functional profile length (2.1 versus 3.6 cm., respectively, p less than 0.001), maximal urethral closure pressure (39 versus 74 cm. water, respectively, p less than 0.001) and maximal urethral closure pressure during voluntary contraction of the external sphincter (107 versus 172 cm. water, respectively, p less than 0.002). The differences among maximal detrusor pressure, initial bladder volume at which a detrusor contraction occurs, maximal cystometric capacity and residual urine were not statistically significant between the 2 groups. Urethral instability was present in 1 of the 24 incontinent patients (4.2%) and in none of the 13 continent patients, while detrusor instability was present in 6 (25%) and 3 (23.1%), respectively. Urethral and detrusor instability correlated poorly with incontinence (correlation coefficients 0.123 and 0.021, respectively). The appearance of the bladder outlet on voiding cystourethrography was correlated with urodynamic parameters and the presence or absence of continence. Tubularization above the level of the external sphincter was present in continent but absent in incontinent patients. Continence after radical prostatectomy is dependent upon sphincteric efficiency, which may be influenced by the anatomical configuration of the reconstructed bladder outlet and the integrity of the distal urethral sphincteric mechanism. PMID- 2329615 TI - Significance of asymptomatic bacteriuria in spinal cord injury patients on condom catheter. AB - A total of 56 male spinal cord injury patients on condom catheter drainage was studied prospectively within 6 months of the injuries for 5 years. Low bladder pressures (filling maximum 35 cm. water and voiding maximum 70 cm. water) were ascertained with video-urodynamics. External sphincterotomy was performed when necessary for detrusor-sphincter dyssynergia. Yearly upper tract imaging, serum creatinine levels and urine cultures were obtained. All patients had colonized urine (asymptomatic) during the entire study period. No patient sustained deterioration of the urinary tract on imaging or by serum creatinine determinations during the 5-year interval. We conclude that asymptomatic bacteriuria is of no consequence to the integrity of the upper urinary tract when low pressures are operant. PMID- 2329616 TI - Continent urinary diversion in childhood. AB - We review 24 children and young adults who underwent continent urinary diversion. The indications for an operation included bladder exstrophy in 11 patients, myelomeningocele in 8, sacral agenesis in 3, cloacal anomaly in 1, and traumatic disruption of the bladder neck and urethra in 1. The operations performed included an Indiana pouch in 19 patients, including 12 whose stoma was brought to a perineal position and 7 whose stoma was placed in the anterior abdominal wall. A Kock pouch was used in 2 patients and the Mitrofanoff principle was used in 3. The particular indications for the different procedures are discussed at length. Postoperative daytime continence as defined by at least 4 hours of dryness is present in all 24 patients to date, while 4 have nocturnal incontinence. Renal function is stable in all patients to date. In 18 patients postoperative urine cultures were positive during followup. All patients are on clean intermittent catheterization and reoperation has been required in 2 relating to an inability to perform postoperative intermittent catheterization. Two patients underwent reoperation for small bowel obstruction. The series supports the use of continent urinary diversion as a viable alternative to traditional forms of conduit diversion in children and young adults. PMID- 2329617 TI - Bladder function in patients with lipomyelomeningocele. AB - We evaluated preoperative and postoperative bladder function in 31 consecutive patients who underwent definitive operative correction of lipomyelomeningocele. Of 12 patients less than 1.5 years old at operation, bladder function was normal preoperatively and postoperatively in 5 (42%) and normalized postoperatively in 4 (33%). In 5 patients (42%) abnormal urodynamic findings were the only sign of neurological abnormality. Of the 19 patients older than 1.5 years at operation bladder function was normal preoperatively and postoperatively in only 4 (21%), and normalized postoperatively in none. We conclude that the majority of patients with lipomyelomeningocele have bladder dysfunction, and that in some cases this dysfunction can be prevented and/or reversed by early neurosurgical intervention. Urodynamic assessment is helpful as part of the neurological evaluation and in directing patient care. PMID- 2329618 TI - Success of the artificial urinary sphincter after failed surgery for incontinence. AB - We implanted the artificial urinary sphincter in 15 incontinent patients for whom multiple urethral and bladder neck operations, including sphincter placement, had been unsuccessful. The 5 male and 10 female patients ranged from 3 to 26 years old (mean age 11 years). The etiology of incontinence was neurogenic bladder in 10 patients, epispadias in 2, exstrophy in 1, ectopic ureters in 1 and traumatic urethral disruption in 1. Of the 15 patients 13 required augmentation enterocystoplasty and clean intermittent catheterization. The initial anti incontinence procedures were Young-Dees-Leadbetter bladder neck reconstruction in 10 patients, artificial urinary sphincter placement in 4 and bladder neck suspension in 1. Causes of failure of the primary treatment were erosion (artificial urinary sphincter), and incontinence and/or difficult catheterization (Young-Dees-Leadbetter). Followup from the last salvage operation averaged 21 months (range 6 to 37 months). A total of 58 operations was performed. Among the 4 patients in whom the artificial urinary sphincter eroded the bladder neck repeated attempts to place the cuff at the same site were unsuccessful and erosion occurred in all 4 within 1 year. Sphincter placement was more successful among the 11 patients who initially underwent Young-Dees-Leadbetter bladder neck reconstruction or bladder neck suspension; acceptable continence was attained in 8 patients (73%). We conclude that placement of the sphincter cuff around a previously eroded bladder neck probably will result in erosion. Sphincter implantation should be attempted in patients in whom bladder neck reconstruction has failed. Persistence in the treatment of these patients is essential because multiple operations often are necessary to achieve continence. PMID- 2329619 TI - Leiomyoblastoma of the epididymis in a child. AB - A case of leiomyoblastoma of the epididymis in a 3-year-old boy is presented. Left high inguinal orchiectomy was performed. Light and electron microscopic examinations revealed a 3.5 X 2.3 X 1.5 cm. tumor continuous with the tail of the epididymis. The lesion proved to be a leiomyoblastoma of the epididymis. Leiomyoblastoma is a form of leiomyoma mainly composed of immature smooth muscle cells. The absence of keratin, epithelial membrane antigen and negative results by alcian blue stain indicated that there were no adenomatoid elements in the tumor. PMID- 2329620 TI - Even 'in perspective,' HIV specter haunts health care workers most. PMID- 2329621 TI - NIH 'Research Risks Office' reprimands hospital institutional review board. PMID- 2329622 TI - From the Food and Drug Administration. PMID- 2329623 TI - From the Centers for Disease Control. World no-tobacco day. PMID- 2329624 TI - From the Centers for Disease Control. Moth-associated dermatitis--Cozumel, Mexico. PMID- 2329626 TI - California bill seeks resident work hour limits. PMID- 2329625 TI - From the Centers for Disease Control. Change in administration schedule for Haemophilus b conjugate vaccines. PMID- 2329627 TI - Is abuse a learned skill? PMID- 2329628 TI - A national health program. PMID- 2329629 TI - The runaway American health care system. PMID- 2329630 TI - Pediatric trauma: getting triage right. PMID- 2329631 TI - Underreporting of AIDS in South Carolina. PMID- 2329632 TI - Postsurgical mortality in Manitoba and New England. AB - Per capita hospital expenditures in the United States exceed those in Canada, but little research has examined differences in outcomes. We used insurance databases to compare postsurgical mortality for 11 specific surgical procedures, both before and after adjustment for case mix, among residents of New England and Manitoba who were over 65 years of age. For low- and moderate-risk procedures, 30 day mortality rates were similar in both regions, but 6-month mortality rates were lower in Manitoba. For the two high-risk procedures, concurrent coronary bypass/valve replacement and hip fracture repair, both 30-day and 6-month mortality rates were lower in New England. Although no consistent pattern favoring New England for cardiovascular surgery was found, the increased mortality following hip fracture in Manitoba was found for all types of repair and all age groups. We conclude that for low- and moderate-risk procedures, the higher hospital expenditures in New England were not associated with lower perioperative mortality rates. PMID- 2329633 TI - Treatment failure after substitution of generic pancrelipase capsules. Correlation with in vitro lipase activity. AB - Pancreatic enzyme products are formulated, manufactured, and sold without submitting efficacy or bioavailability data to the Food and Drug Administration because of a quirk in the law. We documented therapeutic failures in three patients with cystic fibrosis after pharmacists substituted generic pancrelipase capsules for the Pancrease brand. Gastrointestinal symptoms and fat malabsorption rapidly resolved after therapy was reinstituted with brand name products. In vitro analysis indicated that after 1 hour of exposure to simulated gastric fluid, lipase activity was less than 200 U per capsule from all three generic capsules dispensed to the patients compared with 6820 U per capsule from Pancrease. These data indicate that the enteric coating of the generic product was defective and that the substituted product was not bioequivalent to the prescribed brand. We conclude that the Food and Drug Administration should institute regulations over this group of products. PMID- 2329635 TI - Ectopic hyperprolactinemia resulting from an ovarian teratoma. AB - Detection of an elevated prolactin level in the nonpregnant patient usually directs attention to the investigation of the pituitary gland. We describe a patient with secondary amenorrhea and galactorrhea in whom such an elevated prolactin level did initially lead to the discovery of a pituitary mass that was treated first unsuccessfully with surgery, and then successfully with medical therapy. After medical therapy normal menstruation continued, galactorrhea recurred intermittently, and the prolactin level rose again and remained in the approximately 36-micrograms/L range. However, 2 years later an ovarian teratoma was discovered incidentally and was removed surgically. On pathological evaluation the teratoma was noted to include prolactin-containing tissue, and immediately after surgery the patient's prolactin level and responsiveness to stimulatory testing returned to normal. To our knowledge this is the first case report of the association of clinically evident hyperprolactinemia with an ovarian cystic teratoma that contained prolactin-producing tissue. PMID- 2329636 TI - Polycythemia vera. PMID- 2329634 TI - The effects of polyunsaturated fat vs monounsaturated fat on plasma lipoproteins. AB - The effect on plasma lipoproteins of exchanging fat type within currently recommended reduced-fat diets was studied in a free-living group of 19 men and 20 women who consumed both a polyunsaturated fat-enriched diet and a monounsaturated fat-enriched diet, each for a 12-week period, with saturated fat and cholesterol held constant. Mean plasma concentrations of low-density lipoprotein cholesterol and low-density lipoprotein total mass (analytic ultracentrifuge), and high density lipoprotein (HDL) cholesterol and HDL total mass, did not change significantly on exchanging fat type. However, HDL2 cholesterol concentration was 50% higher and HDL3 cholesterol concentration was 7% lower for polyunsaturated compared with monounsaturated fat. Mean total mass of HDL2 was also 23.5% higher and concentration of apolipoprotein B was 5.4% lower on transfer to the polyunsaturated fat diet. Contrary to frequent assertions, we find no advantage with respect to plasma HDL concentrations in using predominantly monounsaturated rather than polyunsaturated fats in subjects who consumed reduced-fat, solid-food diets. PMID- 2329637 TI - A national health program. Abyss at the end of the tunnel--the position of physicians who care. PMID- 2329638 TI - Regulatory status of pancreatic enzyme preparations. PMID- 2329639 TI - Comparing benefits and harms: the balance sheet. PMID- 2329640 TI - National morbidity data have their beginnings in offices of private practice physicians. PMID- 2329641 TI - Messages prove 'you can do that on television'. PMID- 2329642 TI - And on the farm... PMID- 2329643 TI - Taking nation's pulse through surveys. PMID- 2329644 TI - Contempo '90. PMID- 2329645 TI - Contempo '90. PMID- 2329646 TI - Administrative medicine. PMID- 2329647 TI - Adolescent medicine. PMID- 2329648 TI - Allergy and immunology. PMID- 2329649 TI - Cardiothoracic surgery. PMID- 2329650 TI - Dermatology. PMID- 2329652 TI - Emergency medicine. PMID- 2329651 TI - Economics. PMID- 2329653 TI - Endocrinology. PMID- 2329654 TI - Ethics. PMID- 2329655 TI - Family practice. PMID- 2329656 TI - Geriatric medicine. PMID- 2329657 TI - Internal medicine. PMID- 2329658 TI - Medical education. PMID- 2329660 TI - Neonatology. PMID- 2329659 TI - Medical genetics. PMID- 2329662 TI - Neurology. PMID- 2329661 TI - Neurological surgery. PMID- 2329663 TI - Nutrition. PMID- 2329664 TI - Obstetrics and gynecology. PMID- 2329666 TI - Oncology. PMID- 2329665 TI - Occupational medicine. PMID- 2329667 TI - Ophthalmology. PMID- 2329668 TI - Otolaryngology-head and neck surgery. PMID- 2329669 TI - Pathology. PMID- 2329670 TI - Preventive medicine. PMID- 2329671 TI - Psychiatry. PMID- 2329672 TI - Pulmonary medicine. PMID- 2329673 TI - Quality assurance. PMID- 2329675 TI - Substance abuse. PMID- 2329674 TI - Radiology. PMID- 2329676 TI - Surgery. PMID- 2329677 TI - Transplantation. PMID- 2329678 TI - [Analysis of adhesive proteins on the surface membrane of platelet in malignant neoplasm]. AB - Flow cytometry was used to detect fibrinogen (platelet associated fibrinogen: PAFbg) and fibronectin (PAFn) on the surface membrane of platelets in leukemia (9 cases), lung cancer (15 cases) and hepatoma (8 cases) patients (by one color analysis method), and simultaneously to investigate the binding of monoclonal anti-glycoprotein (GP) IIb/IIIa and anti-GP Ib antibodies (by two color analysis). All patient groups showed higher Fbg values than the normal control group, but no differences were found between patient groups. The values of Fbg and Fn showed a correlation, but the pattern of binding did not show a regular tendency in any patient group. There also was no significant correlation between Fbg values and the positive percentage of monoclonal anti-GPIIb/IIIa and anti GPIb antibodies, and the binding of Fbg did not inhibit that of monoclonal antibody. The results suggest the following. 1. There are no differences in platelet activation in leukemia, lung cancer and hepatoma patients, and the degree of platelet activation is decided by the degree and the kind of stimulation. 2. The increase of both PAFbg and PAFn prove to the existence of activated platelet. PMID- 2329679 TI - [Prognostic factors in aplastic anemia. A statistical analysis of 105 cases]. AB - We analyzed 105 cases of aplastic anemia diagnosed between 1958 and 1985 to clarify the variables that are related to prognosis. The most significant variable at diagnosis was reticulocyte count, followed in order by percent bone marrow lymphocyte, red cell turnover rate, T-score severity grade, iron utilization and aplastic anemia study group (AASG) severity grade. Reticulocyte count was the single significant variable in multivariate analysis. Three months after diagnosis, the most significant variable was still the reticulocyte count, followed by AASG severity grade. Changes of variables during the 3 months were not correlated to prognosis. Our result reconfirmed that reticulocyte count was the most important variable related to prognosis. PMID- 2329680 TI - [Hodgkin's disease associated with Tolosa-Hunt syndrome]. AB - A thirty-eight-year-old man developed gradually progressing right retro-orbital pain, diplopia on the left lateral gaze, and left ptosis. On examination paresthesia was present on the first division of right trigeminal nerve. Orbital venography revealed obstruction of right superior orbital vein on the entering portion to the cavernous sinus. A daily administration of 30 mg of prednisolone resulted in a rapid improvement of the symptoms. Diagnosis of Tolosa-Hunt syndrome was made on the basis of neurological symptoms, roentgenographic findings and responsiveness to prednisolone. One year later, weakness of right leg accompanied with left cervical and axillary lymphadenopathy was developed. A biopsy specimen of cervical lymph node was identical with the Hodgkin's disease, lymphocyte predominance type. He was treated with COPP regimen; lymphadenopathy decreased in size. We reported a rare case of Hodgkin's disease preceded by Tolosa-hunt syndrome which might be caused by the extranodal lesions. PMID- 2329681 TI - [A Japanese family with hereditary HbH disease--a case report and its gene analysis]. AB - Hereditary HbH disease was found in a Japanese family. The propositus showed hypochromic microcytic anemia and chronic hemolysis. HbH inclusion bodies were detected in red cells, and an abnormal band corresponding HbH was found in an isoelectric focusing of the hemolysate. Gene analysis of the propositus revealed double heterozygosity for alpha + and alpha zero thalassemias. Four of six his siblings shared the alpha zero thalassemia and one the alpha + thalassemia. Another one was normal. The alpha + thalassemia was of 3.7 kb-deletion type and alpha zero was close to Southeast Asian type. This is the fourth Japanese family with hereditary HbH disease. PMID- 2329682 TI - [Acute renal failure following dehydration and hemolytic crisis due to pneumonia in a case of PNH]. AB - A 41-year-old female, who had been diagnosed as having paroxysmal nocturnal hemoglobinuria (PNH) in 1985, was admitted to our hospital with cough, fever, diarrhea, vomiting and palpitation in April 1988. The chest X-ray showed pneumonia in her right lung. In the peripheral blood, red blood cell count was 1.64 x 10(6)/microliters, hemoglobin 4.7 g/dl and reticulocytes 19%. The levels of serum LDH, indirect bilirubin and creatinine were high. Pneumonia improved by the administration of antibiotics, however, anemia and renal failure deteriorated. After washed red blood cell transfusions totalling 2,000 ml and six times of hemodialysis, renal function returned to normal. This patient with PNH appeared to have developed acute renal failure by dehydration and hemolytic crisis due to pneumonia. PMID- 2329683 TI - [Primary myelofibrosis with extramedullary haematopoiesis of the skin transformed into acute megakaryoblastic leukemia]. AB - A 70-year-old man, who had been diagnosed as primary myelofibrosis in 1987 at Tokyo Women's Medical School, was admitted to our hospital because of left hip joint pain in May 1988. Physical examinations revealed marked hepatosplenomegaly and multiple reddish papules on the skin. The peripheral blood showed marked leukoerythroblastosis and severe anemia with poikilocytosis. Bone marrow aspirations were dry tap. Needle biopsy of iliac crest showed a diffuse fibrosis. Biopsy of the papules showed an extramedullary haematopoiesis. He was treated with low dose Ara-C for seven days. Although hepatosplenomegaly and skin papules were reduced, he died of pneumonia a month later. At autopsy, leukemic cells massively infiltrated into the multiple organs, including bone marrow. The cells were identified with megakaryoblast, as those were positive for factor VIII related antigen. As far as we know, this is the third case of primary myelofibrosis transformed into acute megakaryoblastic leukemia. PMID- 2329684 TI - [Accessory use of protease-inhibiting agents for disease remission in a patient with autoimmune hemolytic anemia associated with B-CLL]. AB - Protease inhibiting agents, which have inhibitory effects on complement system, were used to treat a patient with autoimmune hemolytic anemia (AIHA) associated with B cell chronic lymphocytic leukemia (B-CLL). Although this patient had failed to respond thoroughly to prednisolone, the additional use of protease inhibitors induced a disease remission of hemolytic anemia. The result suggests that complement components are of importance in the pathogenesis of hemolysis in AIHA, and supports the accessory use of protease inhibiting agents in autoimmune hematologic diseases associated with the complement activation and hypersplenism. PMID- 2329685 TI - [Cardiac tamponade as an initial manifestation of acute myeloblastic leukemia]. AB - A 28-year-old man was admitted to our hospital because of cardiac tamponade and pleural effusion. Although his peripheral blood picture was normal, his pericardial fluid contained a lot of myeloblasts with Auer bodies and a diagnosis of acute myeloblastic leukemia (M2) was made from the finding of bone marrow smears. The pericarditis was successfully treated with instillation of mitoxantrone into the pericardial space after drainage. He responded well to the systemic chemotherapy and achieved a complete remission. Although 27 cases of leukemia complicated with cardiac tamponade have so far reported, only three cases gave normal findings of the peripheral blood on admission. Leukemic pericardial effusion with cardiac tamponade in very rare as an initial manifestation of AML. The efficacy and safety of pericardial infusion of mitoxantrone were demonstrated in this patient. PMID- 2329686 TI - [Two cases of familial occurrence of aplastic anemia]. AB - It is quite rare that aplastic anemia except Fanconi's type occurs in members of a single family. Here we reported two patients with aplastic anemia, a 14-year old female and a 49-year-old her mother. In both cases, hematological findings were compatible to that of a typical aplastic anemia. In the case of daughter, CFU-E formation of control bone marrow cells was significantly inhibited by the addition of the patient's bone marrow cells, suggesting the presence of cellular immune mechanism. In the case of mother, no inhibitory activity on CFU-C formation of control bone marrow cells was detected in the patient's serum, though the ratio of helper/suppressor T lymphocytes in the peripheral blood was increased. We could not sufficiently clarify the common immune mechanism causing aplastic anemia in both cases. It was noticeable, however, that both cases share HLA DR2, which is frequently found in patients with various autoimmune diseases and is believed to relate closely to the pathogenesis of autoimmune diseases. This evidence suggests the possibility that genetically inherited susceptibility may also be the important factor for causing aplastic anemia. PMID- 2329687 TI - [Acute myelomonocytic leukemia with mastocytosis in bone marrow]. AB - A 22-year-old female was admitted to our hospital because of general fatigue. The lymph nodes, liver and spleen were not palpable. She was without cutaneous lesions. Haematological examinations revealed leukocytes 3,200/microliters with 44% blasts of myelomonocytic origin, and platelets 15,000/microliters. Bone marrow smears were hypercellular marrow with 51% blasts of myelomonocytic origin and focal involvement of mast cells. Serum histamine and vitamin B12 level was high. Mast cells were round with rounded or segmented nuclei. The nucleoli were inconspicuous and the cytoplasm contained a number of metachromatic granules. Cytochemically, mast cells stained positive for alpha-naphthol-AS.D-chloroacetate esterase and acid phosphatase, and negative for peroxidase, Sudan black B and alpha-naphthyl butylate esterase. In toluidine blue staining, mast cells had stained similarly with pH values from 2.5 to 6.5. She was diagnosed as acute myelomonocytic leukemia with benign mastocytosis, and treated with BH.AC-DNP. A complete remission was obtained, but mast cells in the marrow did not decrease. Relationship between leukemia and mastocytosis was not known, but it was suggested that mast cells responded to the proliferation of the leukemic cells. PMID- 2329688 TI - [Successful induction chemotherapy after colectomy in a case of acute lymphoblastic leukemia associated with obstructive ileus caused by sigmoid colon carcinoma]. AB - We report here a patient who was diagnosed as having acute lymphoblastic leukemia (ALL-L2) and colon carcinoma simultaneously and a successful operation for the colon carcinoma was performed preceded to the treatment of ALL. The patient was a 43-year-old male who presented with acute abdominal symptoms and was diagnosed as ALL by the hematological examination and as colon carcinoma (well differentiated adenocarcinoma, Borrmann II) by colon fiberscope. The patient was underwent sigmoidcolectomy for colon carcinoma and was received antibiotics as well as recombinant human granulocyte colony-stimulating factor (rhG-CSF), Approximately two weeks later, the patient received AdVP (Adriamycin, vincristine, and prednisolone) for ALL and achieved a complete remission. It might be possible for some leukemia patients manifesting acute abdominal symptoms to perform surgical approaches, since the prognosis of leukemia patients improved and supportive therapies, including an application of rh-CSF, have developed. PMID- 2329689 TI - [Megaloblastic anemia and platelet function--a qualitative platelet defect in pernicious anemia]. AB - In order to know the entities of platelet defect in pernicious anemia, we investigated platelet functions in ten cases with pernicious anemia. Three of the cases had total gastrectomy. Five cases showed thrombocytopenia and four cases revealed prolongation of Ivy bleeding time. Decreased adhesiveness was observed in three cases. Various abnormalities in platelet aggregation were observed. However, almost all of the cases showed remarkable improvement of decreased platelet functions after the therapy of Vitamin B12 injection. The results of adenine nucleotides in platelets and the release of them following collagen or epinephrine aggregation were analysed in comparison with normal platelets. The ADP was definitely decreased and the ATP/ADP ratio was increased. In addition, the release of ATP and ADP at collagen or epinephrine induced aggregation was markedly decreased, and after the therapy of Vitamin B12, the decrease of adenine nucleotide release remarkably increased. In summary, the acquired defects of platelet function in pernicious anemia are regarded as a secondary storage pool disease, and its defects improve after Vitamin B12 therapy. PMID- 2329690 TI - [Idiopathic autoimmune hemolytic anemia successfully treated with danazol]. AB - A 50 year old female suffered from idiopathic autoimmune hemolytic anemia. She was initially treated with prednisolone, and anemia was improved moderately. However, maintenance of Hb value was difficult with the decreased dosage of prednisolone. She was subsequently administered danazol, and anemia was completely improved. It is worth to use danazol for the treatment of the patient of autoimmune hemolytic anemia who is refractory to prednisolone therapy. PMID- 2329691 TI - [Hemophagocytic syndrome in two elderly men]. AB - Case 1: A 68-year-old male, who was admitted to our hospital because of massive intestinal bleeding, died 1 day after admission. Case 2: An 80-year-old male, who was admitted to our hospital because of a loss of consciousness, died 4 days after admission. In both cases prodromic infection was not detected. At autopsy, phagocytosis of RBC and WBC by histiocytes was shown markedly in the spleen in case 1 and in the bone marrow in case 2. So diagnosis of virus-associated hemophagocytic syndrome was made. It might be related to some underlying immunologic derangement, because both cases were in advanced age. PMID- 2329692 TI - [Heart rate control and determinant factors]. PMID- 2329693 TI - [Electrophysiologic study for pacemaker implantation]. PMID- 2329694 TI - [Cardiac function and hemodynamics in patients with artificial pacemakers]. PMID- 2329695 TI - [Pacemaker technology--present and future trends]. PMID- 2329696 TI - [Guidelines for permanent cardiac pacemaker implantation. A report of the Joint American College of Cardiology/American Heart Association Subcommittee on Pacemaker Implantation]. PMID- 2329697 TI - [Indication for cardiac pacing in A-V block and fascicular block]. PMID- 2329698 TI - [Sick sinus syndrome--indication of pacemaker implantation]. PMID- 2329699 TI - [Indications and choice of implantable pacemaker for bradyarrhythmias other than AV block and sick sinus syndrome]. PMID- 2329700 TI - [Temporary pacing for bradycardia--indication, method and technique]. PMID- 2329701 TI - [Management of complications in cardiac pacing]. PMID- 2329703 TI - [Electrophysiologic study of tachyarrhythmias and antitachycardia pacing]. PMID- 2329702 TI - [Patient care for cardiac pacing--longevity and quality of life]. PMID- 2329704 TI - [Electrophysiologic mechanisms of termination of reentrant tachycardias by anti tachycardiac pacemaker]. PMID- 2329705 TI - [Functional comparison of respective antitachycardia pacemakers]. PMID- 2329706 TI - [Optimal pacing for termination of paroxysmal supraventricular tachycardia]. PMID- 2329707 TI - [Hemodynamic concept of physiological pacing and clinical benefits with DDD pacemaker]. PMID- 2329709 TI - [The indication, complications and contraindication for DDD pacing]. PMID- 2329708 TI - [Heart function and hemodynamics in DDD pacing]. PMID- 2329710 TI - [The causes of heart rate variation and determinant for rate responsive pacing]. PMID- 2329711 TI - [Activity sensing rate responsive pacemaker]. PMID- 2329712 TI - [Respiratory rate dependent pacemaker]. PMID- 2329713 TI - [T wave sensing problems with rate responsive pacemaker using Q-T interval and clinical experience]. PMID- 2329714 TI - [Central venous temperature sensing]. PMID- 2329715 TI - [Development of multisensor rate responsive pacemaker]. PMID- 2329716 TI - [Usefulness of different types of rate responsive pacemakers]. PMID- 2329717 TI - [Advances of immunohistochemistry and its application to histopathology--studies on liver metastasis of colorectal carcinoma--venous basement membrane laminin]. AB - Recently developed immunohistochemical techniques are revolutionizing surgical pathology. Although much has been written describing sensitivity and specificity of reagents in the relationship to given diagnoses, little has been published regarding the evaluation in diagnostic histopathology. Of 4905 cases, immunohistochemical stains were done in our laboratory on 108 cases in 1988. Forty three markers of different kinds were used for 266 specimens. The mean number of markers used in one case was 2.5. Evaluation study of these cases revealed good to limited diagnostic value of immunohistochemical procedures in about 70% of those cases, but no diagnostic value in approximately 30% of the cases. Relationship between venous invasion and basement membrane was investigated to clarify the mechanism of liver metastasis of the colorectal carcinoma by histologically and immunohistochemically using the anti-laminin antibody. Ninety cases of colorectal carcinoma with liver metastasis were studied. Venous invasion was found in 60 of 66 cases of synchronous liver metastasis, and in 14 of 24 cases of metachronous liver metastasis. Venous invasion was considered highly significant to development of liver metastasis, though there was a definite difference in several aspects between the two groups. Well-defined laminin-containing basement membrane was found in the primary tumor in 35 of 90 cases and in metastatic foci in 15 of 28 cases in which examination was performed. It was most frequently seen in well differentiated adenocarcinoma, though statistically not significant compared to moderately differentiated adenocarcinoma. No definite correlation was found between development of liver metastasis and basement membrane associated tumor cells. PMID- 2329718 TI - [Plasma noradrenaline response to phentolamine in "latent" left-sided heart failure]. AB - To estimate the pumping function of the left-sided heart in patients with "latent" left-sided heart failure due to heart disease which primarily affected the left-side of the heart (former NYHA class I and II), we measured (i) the increase of peripheral venous pressure in response to supine mild leg exercise (delta VP), and (ii) the increase of plasma noradrenaline (NA) concentration due to phentolamine (PH) injection (delta NAPH). We divided the patients into well functioning left-sided heart group (delta CI/delta PAW greater than 0.180 L.min 1.M-2.mmHg-1) and poorly-functioning left-sided heart group (delta CI/delta PAW less than or equal to 0.180 L.min-1.M-2.mmHg-1) on the basis of a ratio (delta CI/delta PAW), relating the increase in cardiac index (delta CI) in response to exercise to the concomitant increase in mean pulmonary artery wedge pressure (delta PAW). This diving line (delta CI/delta PAW = 0.180 L.min-1.M-2.mmHg-1) correlated with delta VP (diving line: delta VP = 35 mmH2O) and with delta NAPH (diving line: delta NAPH = 0.353 ng/ml). Our results suggest that delta VP and delta NAPH reflected the pumping function of the left-sided heart with considerable accuracy. PMID- 2329719 TI - [Pre- and postoperative care of living relative patients for renal transplantation]. AB - Between 1966 and 1989, 54 kidney transplants were performed at our institute. We present our experience about pre- and postoperative care of the patients for renal transplantation. 1) Donors 1) Pre- and postoperative function of the kidneys and urinary tract must be evaluated carefully. Renal transplantation can be done successfully if preoperative renal function is good even if the donor is older than 60 years old. 2) Preoperative evaluation of the donor renal artery is necessary. Four kidneys with renal artery anomalies and one kidney with renal artery aneurysm were used for renal transplantation uneventfully after they were repaired. 2) Recipients 1) We had 4 recipients who demonstrated abnormality of the urinary tract. They all received successful renal transplantation after appropriate urological management before renal transplantation. 2) Imaging diagnostic technique is useful when graft function is deteriorated. Acute rejection can be diagnosed more objectively using renal scintiscan and echogram. They are also useful for early detection of postoperative urological complications. In this paper, the diagnostic strategy using various imaging techniques was outlined. PMID- 2329720 TI - [Pathologic diagnosis of renal transplantation]. AB - Eighty-seven renal allografts were examined at our department between 1980 and 1989. In these specimens, 24 cases involved so-called "1 hour biopsy", including a case of donor carrying IgA nephropathy. Nine cases showed glomerulonephritis, of which three cases are suspected as de novo membranous nephropathy. Acute rejection, glomerular, tubular and vascular type were seen in 11 cases, and chronic rejection in 20 cases. Four cases showed tubular injury which may be associated with cyclosporine nephrotoxicity. At diagnosis of acute cellular rejection, immunohistological analysis was performed to characterize the composition of the micronuclear cells. In all cases we examined, T lymphocyte is dominant, and CD8+ (Leu 2) cells and CD4+ (Leu 3) cells were seen in various percentages. The Leu M1(+) macrophage was also seen in glomerular capillary lumen or peritubular space. Whether the expression of HLA-DR antigens is altered in renal transplants was examined. Expression of DR antigens increased considerably on renal tubular cells and glomerular capillary endothelial, and may be a markers of acute rejection. PMID- 2329721 TI - [The frequency of patients with positive HIV-antibody in the various groups and the prognosis of these patients treated with SNMC]. AB - Among 300 patients receiving blood and/or blood products because of blood disorders, 3 (1%) were positive for HIV by ELISA. However, 3 patients were thought to be false positive because they had received bolus injection of gamma globulin and their serum became negative after 6 months. Moreover, no viral inclusion or HIV-antigen was detected. In 30 patients with hemophilia and related disorders, 21 (70%) were positive by ELISA, Immunofluorescence, Passive agglutination and Western Blot method. Immunodeficiency, as reflected by decreases of CD 4/8 ratio and NK activity, was successfully treated with high dose of Stronger Neo-Minophagen C. PMID- 2329722 TI - [Analysis of cross-linked fibrin and fibrinogen degradation products with SDS PAGE and immunoblot]. AB - SDS-PAGE and immunoblot technique with anti-FDP-D, -FDP-E, -fibrinogen antibody or anti-FDP-DD monoclonal antibody were applied to analyze FDP fragments prepared from cross-linked fibrin and fibrinogen with plasmic digestion in vitro. FDP fragments of DY(260K), DD(187K), X(245K), Y(166K), D(77K, 97K), E1(58K), E2(46K) and E3(40K) were identified from data of molecular weight and reactivity to four antibodies referred to reports of other investigators. Serum FDP fragments from five DIC suspected patients were analyzed by the same methods. In two patients' sera, DD fragment was a main component, and in the other three patients' sera, D fragment was a main fraction. Proportions of high molecular weight fragments of FDP were considerably different in patients' sera. Appearance of D fragment in our cases was considered to be derived from unstable fibrin (fibrin monomer and dimer) rather than from fibrinogen. Molecular weight of DD fragments from patients' sera had heterogeneity (160 approximately 180K), and the values were different from that (187K) prepared from cross-linked fibrin. In conclusion, SDS PAGE and immunoblot analysis of serum fragments of FDP will be an useful technique to investigate the clinical and pathological condition of DIC. PMID- 2329723 TI - [Ultramicroassay of red cell group using Terasaki-plate]. AB - In order to simplify the testing-method of blood groups (ABO, Rh, MN, Ss, P, I, Lewis, Duffy, Kidd and Diego) and the assay of glycosyl transferases activity, we have developed a new method using Terasaki plate (T-plate method), and examined its usefulness in the routine examination. As results followings were obtained: 1) The sensitivity of T-plate method was equal or superior than that of the common method using test-tube. 2) Samples used for T-plate method were smaller in volume compared with those for the common tube test method. 3) The percent of coincidence between T-plate method and tube test method was 100% for ABO, Rh, MN, Ss, P, I, Duffy, Kidd and Diego grouping. They were 98% for Lewis(a) and 96% for Lewis(b) grouping, respectively. These results indicate the superiority of T plate method than the common method using test-tubes in respects of smaller volume of samples, lower price and handling of a large amount of samples. PMID- 2329724 TI - [A case of systemic lupus erythematosus showing abnormal lipoproteins due to accompanied drug induced hepatitis]. AB - We describe here a 28-years-male with AIHA and SLE who had lipid and lipoprotein abnormalities during cholestasis induced by PGE1 administration. High free cholesterol level, 792 mg/dl was found in his serum, and markedly elevated, phospholipid level 1,614 mg/dl. But, LCAT activity was within normal range in this case. An agarose gel electrophoresis of lipoproteins showed abnormal bands which were located in slow alpha 2, pre beta and slow beta, and between beta and origin point. Moreover, it was detected formation of Lp-X from serum of the patient. Serum levels of apoprotein B, C-II, C-III, and E were higher, while apoprotein A-I, A-II were very lower than reference value. From these results, it was suspected that the patient might occur transient abnormal lipid metabolism according to the drug induced hepatic injury. PMID- 2329725 TI - [Biological evaluation of extracellular superoxide dismutase observed in a state of acute gastric mucosal lesions]. AB - In the experimental stress ulcer models of guinea pig superoxide dismutase-like plasma substance increased in plasma. Upon chromatography on heparin-Sepharose, this substance was separated into three fractions; A, without affinity for heparin; B, with intermediate affinity for heparin; C, with relatively strong heparin affinity, and the fraction C was specifically increased by a stress and a heparin injection. Analysis by a polyacrylamide gel electrophoresis (PAGE) of the fraction C revealed SOD activity, whose molecular weight was 135 K in a native state. The fraction C seemed to be the same as extracellular superoxide dismutase (EC-SOD) reported by Marklund. Assuming to the releasing potency of heparin, the major part of EC-SOD in the vasculature was most likely located on endothelial cell surface. A pathophysiological role of EC-SOD released into plasma seemed to be an indicator of endothelial-cell damage by free radicals of endothelial cells and polymorphonuclear neutrophils (PMNs). PMID- 2329726 TI - [A case of fistula of the colon in non-Hodgkin's lymphoma of the spleen]. PMID- 2329727 TI - [The 8 years observation in a case of essential hyperbileacidemia]. PMID- 2329728 TI - [A case of malignant lymphoma manifesting severe liver injury as an initial sign]. PMID- 2329729 TI - [Studies on the mechanism of restraint-induced gastric ulcer--with special reference to mucosal ischemia and gastric secretion]. AB - Rat gastric mucosal blood flow, hydrochloric acid (HC1) secretion, and morphological changes of parietal cells were studied by light and electron microscopy using histochemical techniques. Mucosal blood flow of restrained rats was remarkably decreased compared with that of control rats, whereas the acetylcholinesterase activity, demonstrated by the method of Karnovsky and Roots, was significantly increased especially near the ulcer. In contrast, the differences in volume, acidity and acid output of gastric juice were not significant between control and restrained rats. Hypersecretion of HC1 induced by a parasympathetic stimulant, bethanechol, was inhibited by blood loss or infusion of cytochalasin B, an actin depolymerizing agent. 14C-aminopyrine accumulation in the primary cultured parietal cells was decreased by the treatment with hypoxia and cytochalasin B. These treatments also prevented the increase of 14C aminopyrine accumulation induced by bethanechol. Actin filaments were evident in the cytoplasm of the parietal cells, particularly around the intracellular canaliculi and beneath the plasma membrane using the FITC-labeled phalloidin reaction and transmission electron microscopic observations of uranyl acetate block stained preparations following heavy meromyosin decorations. Ultrastructural studies of the parietal cells in restrained rats revealed that intracellular canaliculi were dilated with loss of microvilli. Actin filaments were noted to be disassembled, and granular with focal aggregation of actin filaments. Hypoxic vacuoles were also found in the cytoplasm. Treatments with blood loss and cytochalasin B infusion in the in vivo model, and hypoxia and cytochalasin B in the in vitro model, resulted in the similar changes. These observations indicate that actin filaments in the parietal cells of restrained rats may be depolymerized by ischemia. As the result, HC1 secretion would not be enhanced even if the parasympathetic nerves are excessively stimulated in the gastric mucosa. Thus, disturbances of the gastric mucosal microcirculation are considered to be important in the pathogenesis of the stress-induced gastric ulcer. PMID- 2329730 TI - [Absorption disorders following gastric resection--morphological and enzyme histochemical observations on the small intestinal mucosa]. AB - For the purpose of studying digestion and absorption disorders following stomach surgery, particularly with respect to membrane digestive functional disorders, morphological and enzyme-histochemical observation of the small intestinal mucosa was performed, and a comparison was done between the partial gastrectomy group (59 cases), and the total gastrectomy group (52 cases). The following results were obtained: 1) The small intestinal mucosa showed a tendency to significant villous atrophy in post-operative groups. 2) There was a significant decrease in the disaccharidase activity, especially in the small intestine of the total gastrectomy group. ALP, LAP and gamma-GPT activity also decreased, or disappeared in the small intestines showing villous atrophy. 3) In the atrophied mucosa which showed a marked decrease in membraneous enzyme activity, poorly-formed, irregularly sized microvilli accompanied by glycocalyx irregularity and disappearance were recognized under the electron microscope. The above mentioned morphological and enzyme-histological findings in the small intestinal mucosa, were strongly reflected in both post-operative progress and clinical symptoms. PMID- 2329731 TI - [Experimental and clinical studies on liver tissue blood flow in obstructive jaundice]. AB - To clarify some pathologic aspects of obstructive jaundice before and after bile duct drainage, changes in liver tissue blood flow were observed using an electrolytic historheometer, in combination with the FITC-dextran method, during experimental bile duct obstruction and after its elimination. Clinical investigations were based on histologic findings in liver tissue specimens collected by wedge biopsy at the time of laparotomy following bile duct drainage. Rats with bile duct obstruction showed significantly (P less than 0.01) lower values for liver tissue blood flow, with sinusoid dilation, in comparison to control rats, at 2 and 4 weeks following the initiation of experimental bile duct obstruction. Liver tissue blood flow disturbance subsided 3 days after eliminating the obstruction, at 2 weeks following its initiation, while no improvement occurred even following elimination of obstruction after 4 weeks. Clinically, in cases with a high degree of sinusoid dilation the effect of postoperative bile duct drainage was poor, with a high incidence of postoperative complication. These findings suggest that liver tissue blood flow disturbance might causatively affect the pre- and postoperative course of obstructive jaundice. PMID- 2329732 TI - [Biochemical analysis of bone and mineral metabolism in liver cirrhosis]. AB - We investigated the disorder of bone and mineral metabolism in 29 patients with liver cirrhosis who were classified into two subgroups with (group 1, n = 13) or without (group 2, n = 13) osteopenia according to the method of Jikei. Serum levels of osteocalcin level, bone-type alkaline phosphatase activity and calcium concentration in serum and urine in these patients and 25 normal control subjects were determined. Serum osteocalcin level and bone-type alkaline phosphatase activity were elevated in group 1 compared with those in group 2 and normal control subjects. Serum and urine calcium levels in group 1 were similar to those in group 2. However calcium-creatinine ratio in urine was higher in group 1 than in group 2. These present observations indicate that osteopenia in patients with liver cirrhosis is due to high turnover of bone metabolism. PMID- 2329733 TI - [Hepatic mean transit time of 99mTc-EHIDA estimated by deconvolution analysis]. AB - Clinical usefulness of mean transit time (MTT) through the liver was evaluated by deconvolution analysis using 99mTc-EHIDA hepatobiliary scintigraphy in 82 patients with various hepatobiliary diseases and 18 normal controls. Initial transfer factor was also obtained according to the method of Rutland. Results obtained were as follows. 1) Effect of the age on MTT was not observed in normal controls. 2) MTT in left lobe of normal controls was significantly prolonged compared with that of right lobe (P less than 0.01). This kind of difference was not observed in patients with liver cirrhosis. 3) MTT in patients with obstructive jaundice, chronic liver diseases, liver cirrhosis at decompensative state and primary biliary cirrhosis was significantly prolonged compared with that in normal controls (P less than 0.01). 4) MTT in patients with liver cirrhosis at compensative state showed normal values, although blood clearance rate in those patients was significantly decreased (P less than 0.05). 5) Positive correlation was observed between MTT and values of T-Bil, ALP, LAP, and gamma-GTP. Negative correlation was observed between MTT and value of cholinesterase. 6) Initial transfer factor correlated with blood clearance rate. (r = 0.76, P less than 0.01). 7) Initial transfer factor in left lobe of normal controls was significantly decreased compared with that of right lobe (P less than 0.01). This kind of difference was not observed in patients with liver cirrhosis. 8) Initial transfer factor in patients with liver cirrhosis in both compensative and decompensative states and PBC was significantly decreased compared with that in normal controls. Estimation of MTT and initial transfer factor could be a useful parameters to assess transfer function of the liver. PMID- 2329734 TI - [Role of free radicals and lipid peroxidation in gastric mucosal injury induced by ischemia-reperfusion in rats]. AB - Ischemia and reperfusion is of the greatest importance in the pathology of various diseases. This study was designed to investigate the role of oxygen derived free radicals and lipid peroxidation in gastric mucosal injury induced by ischemia-reperfusion in rats. Clamping of the celiac artery in rats reduced the gastric mucosal blood flow to 10% of that measured before the clamping. Gastric mucosal injury, such as spotty and linear hemorrhagic erosions, was seen in rats 60 min of the reperfusion following 30 min of ischemia. Thiobarbituric acid (TBA) reactants in the gastric mucosa were increased after the reperfusion. The increase in gastric mucosal lesions and TBA reactants were significantly inhibited by the treatment with SOD+ catalase and allopurinol. These results suggest that oxygen-derived free radicals and lipid peroxidation may play an important role in the pathogenesis of acute gastric mucosal lesions induced by ischemia-reperfusion. PMID- 2329735 TI - [Estimation of the reticuloendothelial function by positron emission computed tomography (PET) study in chronic liver disease]. AB - We have developed a new liver scanning agent (Ga-68 human serum albumin microspheres) in a convenient kit for use in positron emission computed tomography (PET). In this study, this scanning agent was evaluated for clinical usefulness as a function test for the reticuloendothelial system. A dose of 5 micrograms/kg (1-2 mCi) of Ga-68 microspheres was injected intravenously to 25 patients, 11 with chronic hepatitis and 14 with liver cirrhosis, and 5 normal volunteers for PET imaging of the liver and spleen using HEADTONE-III (SET 120W). The volumes of the liver and the spleen and the uptakes of Ga-68 microspheres were calculated as an index of the reticuloendothelial system function. In liver cirrhosis the liver volume estimated by PET was decreased and the spleen volume was increased. Both the liver uptake rate and differential absorption ratio (DAR) of the radioactivity were decreased corresponding with the degree of chronic liver disease. The spleen uptake rate was increased with progression of chronic liver diseases, but there was no difference in DAR between normal volunteers and patients with chronic liver disease. it was concluded that PET using Ga-68 microspheres is useful in the evaluation of the function of the reticuloendothelial system. PMID- 2329736 TI - [Diagnosis and treatment of mechanical jaundice]. AB - Various instrumental methods of examination were applied in 364 cases with obstructive jaundice. Drainage of the biliary tract in 190 patients was conducted by laparoscopic cholecystostomy, percutaneous, transhepatic cholangiostomy, endoscopic papillosphincterotomy. The results of 167 operations performed at the peak of obstructive jaundice were compared with those of 81 operations undertaken after successful preoperative drainage of the biliary tract. The incidence of complications reduced from 40.5% to 22%, the death rate from 22% to 9.8%. PMID- 2329737 TI - [Transhepatic endoprosthesis of the bile ducts]. AB - The authors analysed the results of percutaneous transhepatic endoprosthetics of the hepaticocholedochus in 38 patients with incurable tumors of the organs of the hepato-pancreato-duodenal zone, complicated by obstructive jaundice. Nine different types of bile ejection blocking were distinguished, according to which the method and tactics of the endobiliary intervention were elaborated. Measures for the prevention of cholangitis, bleeding into the abdominal cavity, and hemobilia in the postoperative period are described in detail. The article shows the results recorded in flow-up periods of one to 11 months in 26 patients who had been subjected to endoprosthetics of the bile ducts and discharged from the clinic for out-patient treatment. Recurrence of obstructive jaundice caused by incrustation of the prosthesis was encountered only in 2 patients 4 and 9 months after the intervention. This allowed the authors to conclude that endoprosthetics of the hepaticocholedochus is very effective in the treatment of patients with obstructive jaundice of neoplastic etiology and to consider a transhepatic intervention an alternative of a surgical operation. PMID- 2329738 TI - [Perforation of malignant tumor of the gallbladder]. AB - Perforative complications in 13 of 274 (4.7%) patients with carcinoma of the gallbladder are analysed. The author describes the specific features of the clinical course of this complication depending on certain factors associated with growth of the tumor and development of the pyogenic process, the types and outcomes of the operations. PMID- 2329739 TI - [Lipid peroxidation and disorders of erythrocyte properties in patients with mechanical jaundice]. AB - Changes in the activity of lipid peroxidation (LPO) and the attendant disorders of the properties of the red cells were studied from the results of examination of 32 patients with obstructive jaundice. The data obtained showed that the LPO processes were markedly activated, which led to changes of the red cell membrane properties--reduction of their electric charge, osmotic resistance, and deformity. All this led to metabolic shifts promoting cell destruction. The efficacy of hemosorption was due to sorption of the LPO toxic products rather than to the removal of bilirubin. PMID- 2329740 TI - [Combined surgery of the large intestine and biliary tract]. AB - The article deals with the experience in the treatment of 204 patients with diseases of the biliary tract who underwent operation for various diseases of the colon. In 147 of them intervention on the colon was carried out simultaneously with cholecystectomy and other operations on the biliary tract. In 57 patients the gallbladder was not removed and in 7 (12.2%) of them the immediate postoperative period was marked by the development of complications connected with a disease of the gallbladder. As a result 3 out of the 57 patients were operated on for a second time. The frequency of postoperative complications among patients who were subjected to combined operations was 46.9%, the death rate- 4.8%. It is important to point out that these indices hardly differed from those in the general group of patients (4.2% and 4.8%, respectively). Thus, cholecystectomy combined with intervention on the colon is admissible and, undoubtedly, expedient because it prevents the development of complications of cholelithiasis in the early postoperative period and saves the patient from undergoing a second operation on the biliary tract later. PMID- 2329741 TI - [Surgical treatment of ascites in cirrhosis of the liver]. AB - A porto-systemic shunt can be created in patients with a stable course of cirrhosis of the liver complicated by varicosity of the esophageal veins and transitory ascites. The formation of a lympho-venous anastomosis is indicated in ascites and impaired lymph drainage from the liver. Interventions minimal in volume (peritoneo-venous shunting, reduction of arterial blood flow, etc.) are indicated in stable or progressive ascites and marked disorders of hepatic function. PMID- 2329742 TI - [Prognostic value and possibilities of the treatment of arterio-portal fistula in tumors of the liver]. AB - Angiograms demonstrated arterio-portal shunts in tumors of the liver in 15 patients. Five patients received symptomatic therapy, all of them died from hemorrhage from varicose esophageal veins in the immediate 2 months. Resection of the liver was performed in 4 patients, 3 of them are alive and in a state of remission. Esophageal hemorrhage developed only in 2 of 6 patients who underwent embolization of the hepatic artery. It is concluded that the prognosis is extremely unfavourable in untreated patients with marked arterio-portal shunting in the hepatic tumor. Such patients must be treated surgically or, if inoperable, by radiologically-guided intervention, which makes it possible to normalize portal hemodynamics in most cases and avoid fatal hemorrhage. PMID- 2329743 TI - [Diagnosis of membrane disorders in acute pancreatitis]. AB - In 110 patients with acute pancreatitis the authors studied the activity of intracellular enzymes in the blood (LDH, CPC, ALaT, ASaT, transamidinase) in a complex with indices characterizing the condition of the membrane cell systems, in particular: activity of acid phosphatase, content of 17-ketosteroids, activity of plasma chemiluminescence, concentration of beta-lipoproteins in blood. Complex study of these indices makes it possible to make a sufficiently objective judgement of the severity of the membrane disorders in acute pancreatitis and verity the form and control the treatment of the disease. PMID- 2329744 TI - [Endogenous toxemia in pancreatic necrosis of alcoholic etiology]. AB - Operation for pancreonecrosis was carried out in 197 patients, in 52 (26.4%) of them the disease was of alcoholic etiology. The disease was marked by severe clinical manifestations with the development of respiratory, hemodynamic, and peritoneal syndromes and their complications, and by psychic disorders. The endo intoxication structure was studied in 13 patients by mass-spectrometry proceeding from alcohol metabolism in the organism. Eleven intermediate products were identified: ethanol, acetaldehyde, normal butyraldehyde and isovaleric aldehyde, diethylamine, acetone, isopropanol, methyl isocyanide, trimethylamine, ethannitrile. It was noted that the clinical manifestations of alcoholic pancreonecrosis are included in the spectrum of ethanol pharmacological action; the content of ethanol in the blood was tenfold of the normal, that of the product of its metabolism acetaldehyde was 1.6 times the normal level. Inclusion of exogenic ethanol in metabolism leads to its distortion and accumulation of substances of different origin in the organism, among which an important role is played by acetaldehyde, normal butyraldehyde, and isovaleric aldehyde. The results of the study create proconditions for the search for a rational means for their desactivation. PMID- 2329745 TI - [Endoscopic diagnosis and treatment of tumors of the major duodenal papilla]. AB - Gastroduodenoscopy with target examination of the major duodenal papilla (MDP) and morphological study of the tumor, and endoscopic retrograde pancreatocholangiography were conducted in 104 patients with bening and malignant tumors of the MDP to establish the diagnosis. A precise diagnosis was made. Endoscopic papillotomy alone and in combination with nasobiliary drainage and endoprosthetics of the bile ducts were undertaken for therapeutic purposes in this category of patients. Analysis of the results showed that in cancer of the MDP, these methods can be the tool of treatment or an effective one of preoperative decompression, whereas in bening tumors of the MDP endoscopic papillotmy should be the method of choice. PMID- 2329746 TI - [Surgical treatment of acute cholecystitis complicated by peritonitis in middle aged and elderly patients]. AB - Peritonitis is among the severe complications of acute cholocystitis; the authors encountered its generalized forms in 10.9% of the patients who were operated on as being critically ill. Gangrenous or perforating cholecystitis was the most frequent cause of peritonitis. The high postoperative death rate (22.4%) caused among elderly and old-aged patients by generalized peritonitis and the necessity of an emergency operation requires intensive preoperative management and complex postoperative treatment with the application of modern detoxification methods in an intensity care department. In view of the high operative-anesthetic risk in patients of the old-age groups, the authors undertook sparing operations for decompression of the gallbladder in generalized peritonitis with the subsequent performance of a radical sanitizing operation in a postponed or planned order. This allowed the postoperative death rate to be reduced to 7.7% in the recent years. PMID- 2329747 TI - [Endovascular diagnosis and transcatheter procedures in portal hypertension]. AB - The results of endovascular diagnosis and transcatheter surgery in 113 patients with various forms and stages of portal hypertension are analysed. A total of 761 diagnostic and 194 therapeutic radiologically-guided endovascular interventions were carried out. Purposeful study of the arteriovenous angioarchitectonics in the hepato-lienal system, the character and degree of disorders of the portal hepatic hemodynamics, and the peculiar features of collateral circulation before and after various radiologically-guided interventions allowed the authors to elaborate an orderly system of stage-by-stage endovascular treatment of patients suffering from portal hypertension. PMID- 2329748 TI - [Principles of the surgical treatment of suppurative visceral complications of pancreatic necrosis]. PMID- 2329749 TI - [A needle for puncture biopsy of the liver]. PMID- 2329750 TI - [Diagnosis of hiatal hernia]. PMID- 2329751 TI - [A method of temporary hemostasis during surgical correction of traumatic aneurysm]. PMID- 2329752 TI - [Chronic duodenal compression by the mesenteric artery complicated by mechanical jaundice]. PMID- 2329753 TI - [Subserous subcutaneous rupture of the gallbladder]. PMID- 2329754 TI - [Hepato-choledochal cyst]. PMID- 2329755 TI - [Surgical treatment of chronic calculous pancreatitis]. PMID- 2329756 TI - [Amebic liver abscess treated by percutaneous drainage]. PMID- 2329757 TI - [Cholelithiasis--a complication of aortic valve prosthesis]. PMID- 2329758 TI - [Complicated carcinoid tumor of the small intestine]. PMID- 2329759 TI - [Severe polytrauma in a child]. PMID- 2329760 TI - [Central and general hemodynamics in healthy persons during simulated weightlessness]. AB - The pumping and contractile functions of the left ventricle were investigated during combined exposure to water immersion and head-down tilt (at -6 degrees) that simulated microgravity. This 7-day exposure caused noticeable changes in central and systemic circulation which developed as a function of time. It is assumed that the deficiency of venous blood return seen on test days 1-3 was a compensatory response to initial blood displacement which was induced by a reduction of the circulating blood volume. The reduction was in turn a result of responses from volumoreceptors of the heart and intrathoracic vessels to "excessive" intrathoracic blood volume. PMID- 2329761 TI - [Correlations of cardiorespiratory and metabolic reactions in humans with graded physical load]. AB - Bicycle ergometry tests of graded workloads were performed by 9 healthy men, aged 25 to 40 years. During the tests cardiorespiratory parameters, lactate and pyruvate concentrations, as well as lactate dehydrogenase (LDH) and NADP dependent isocitrate dehydrogenase (ICDH) activities were measured. It was shown that the threshold of anaerobic metabolism can be measured not only by traditional methods (with respect to variations in pulmonary ventilation and venous blood lactate) but also in terms of ICDH increase as a function of the workload. Mathematical processing of the resulting data did not reveal a correlation between the total oxygen debt and lactate in blood. In contrast, a close correlation between the debt and LDH activity at the end of the test was found. These observations have demonstrated that biochemical measurements should find a wider application in evaluations of energy costs of various workloads. PMID- 2329763 TI - [Genetic studies of Arabidopsis seeds during space flight]. AB - The results of Arabidopsis investigations carried out on various space vehicles are summarized. It is found that space flight effects induce different genetic lesions in seed germs which may decrease plant viability and fertility and increase mutation frequency. The lethal effect of space flight is dependent on its duration and is related to accelerated seed aging. PMID- 2329762 TI - [Activity of various oxidases and transaminases in the rat liver in the readaptation period after hypokinesia up to 30 days]. AB - The activity of alpha-ketoglutarate dehydrogenase and succinic dehydrogenase in readaptation after 15-day hypokinesia was within normal limits, whereas following 30-day hypokinesia it was enhanced on days 11-15. Pyruvate dehydrogenase exhibited hyperactivity in the end of readaptation week 2 both in 15- and 30-day hypokinesia which resulted in rat liver hyperactivity of glutamate dehydrogenase and transaminases. Normal levels of the latter were recorded on readaptation day 12-19. PMID- 2329764 TI - [Effect of outer space factors on lettuce seeds (Lactuca sativa) flown on "Kosmos" biosatellites]. AB - The effect of cosmic radiation on air-dry lettuce (Lactuca sativa) seeds was investigated. It was attempted to discriminate the effects of cosmic ionizing radiation per se and its combination with solar light radiation. It was found that the number of aberrant cells in the seeds exposed to solar light was smaller than that of cells chielded with 0.0008 to 0.0035 g/cm2 foil which could be attributed to photoreactivity. PMID- 2329765 TI - [Effect of a constant high intensity magnetic field on reproductive functions in male rats]. AB - In two experiments male rats were exposed to a constant magnetic field (CMF) of 0.4 T either once for 3 hours or 56 times for the same time (throughout the entire spermatogenetic cycle). During the first week after exposure they were mated with untreated females. Some of the females were sacrificed on their 21st day of gestation. The following parameters were measured: percentage of implantations and resorptions, total fetal lethality, number and weight of alive fetuses, weight of placentas and ovaries, hydration of placentas and fetuses. At birth the duration of gestation, the amount of alive and dead newborns, their weight and distribution in the litter were determined. These parameters were used to evaluate the genetic quality of spermatozoa that were involved in fertilization. The pups were observed during the first month of life. The results obtained suggest that mature spermatozoa are resistant to a single CMF exposure and that this exposure causes no mutations in the gametes which may reduce fetal viability. However, chronic exposure to CMF leads to a small and significant increase of preimplantation lethality of fetuses which may indicate a higher frequency of lethal mutations in the gametes. PMID- 2329766 TI - [Status of the lipid phase of plasma membranes of the rat heart after repeated exposure to an alternate magnetic field of 50 Hz frequency]. AB - The concentration of lipids and spectrum of phospholipids in plasma membranes of hearts of rats exposed for 15 times to intermittent (1:2) alternative magnetic field of 50 Hz and 9.4 mT were measured. This exposure lead to accumulation of lipids and increase of free fatty acids, triacylglycerides, cholesterol esters and phospholipids (although to a smaller extent). The cholesterol/phospholipids ratio decreased significantly. The spectrum of phospholipids was similar to that in the controls, except for phosphatidyl inositol whose content grew. PMID- 2329767 TI - [Resistance of mice to hypoxia of various types and to X-ray radiation in the post-hypoxic period]. AB - Resistance of mice to altitude, gas, hemic, tissue, mixed or hyperoxis hypoxia, to oxidative phosphorylation uncoupling agents and to X-ray irradiation during 2 days after exposure to severe acute hypobaric hypoxia was investigated. No significant changes were found in animal resistance to hemic and tissue hypoxia and to oxidative phosphorylation uncoupling agents. Resistance to hypoxic hypoxia was 2.5 times higher at the 2nd hour of the posthypoxic period and returned to the baseline by the 24 th hour. Resistance to sodium nitrite and potassium persulphate that cause hypoxia of mixed type, to hyperoxia and X-raying increased significantly by the 24th hour and returned to the baseline by the 48th hour of the posthypoxic period. The potential role of the antioxidative system in the induction of resistance to oxidative agents and X-ray irradiation during the posthypoxic period is discussed. PMID- 2329768 TI - [Ultrastructural changes in neurons of the arcuate nucleus-median eminence complex in rats irradiated with carbon ions and gamma rays]. AB - Ultrastructural changes in the arcuate nucleus and medial eminence area of rats were examined 5 weeks after their exposure to accelerated carbon ions with an energy of 300 MeV/nuclon and 60Co gamma-rays at a dose of 2.0 Gy. In carbon irradiated animals the ultrastructural changes of arcuate nucleus neurons, their processes and synapses were more significant and diversified than in gamma irradiated rats. PMID- 2329769 TI - [Use of a "dry" immersion method in the treatment of hypertensive crisis]. AB - The effect of so-called dry immersion on hypertensive patients during hypertensive crisis was investigated. It was demonstrated that after 90-minute immersion blood pressure fell due to beneficial hemodynamic and hormonal changes. This therapeutic method produced a sedative and diuretic effect. The above method of non-drug therapy proves highly effective in the treatment of hypertensive crises of different types, produced no side effects and can be used in a hospital as a cost-effective procedure. PMID- 2329770 TI - [Evaluation of the bioelectric activity of the heart during antiorthostatic hypokinesia using traditional and modified orthogonal ECG leads]. PMID- 2329771 TI - [Algorithms for automatic recognition of basic points in the rheogram]. PMID- 2329772 TI - [Methods of studying intracranial blood and cerebrospinal fluid circulation in chronic experimental decompression sickness]. PMID- 2329773 TI - [Correlation of orthostatic tolerance and vestibular function in man after long space flights]. PMID- 2329774 TI - [Correlation of vertical optokinetic nystagmus and susceptibility to motion sickness in man]. PMID- 2329775 TI - [Evaluation of the operator's readiness for emergency action]. PMID- 2329776 TI - [Effect of space flight factors on the pigment and lipid composition of wheat]. PMID- 2329777 TI - [New standardization documents with regard to radiation safety during space flights]. PMID- 2329778 TI - [The hemostasis system in long-term gamma irradiation at high altitude]. PMID- 2329779 TI - [Medical studies during an 8-month flight on the orbital complex "Saliut-7"- "Soiuz-T"]. AB - This paper presents medical results obtained in a Salyut-7 8-month manned mission in which a physician-cosmonaut took part. The results include body mass and height measurements, vestibular studies, cardiovascular studies at rest and in response to staged functional loads (with echocardiographic examinations accentuated), metabolic and hormonal studies. The paper also gives information about medical aspects of extravehicular activities. It is emphasized that during the mission both old and new methods of research were used and medical results of preceding flights were considered. PMID- 2329780 TI - [Important points in nursing of patients with Guillain-Barre syndrome]. PMID- 2329781 TI - [The burn patient and his care]. PMID- 2329782 TI - [Flexible arrangement of working time in the field of nursing--a contribution to optimal care]. PMID- 2329783 TI - The reliability of functional gain. AB - This study examined the test-retest reliability of unaided and aided sound-field thresholds and the functional gain values derived from these measurements. Sound field warble-tone thresholds were obtained at 250, 1000, and 4000 Hz from 24 hearing-impaired listeners with and without their hearing aids. Test-retest standard deviations were significantly larger for functional gain than for unaided thresholds, but only slightly and nonsignificantly larger than for aided thresholds. The variability of functional-gain measures is discussed in relation to measures of insertion gain obtained with probe-tube microphones. PMID- 2329784 TI - Acoustic reflex thresholds in normal and cochlear-impaired ears: effects of no response rates on 90th percentiles in a large sample. AB - Ninetieth percentile cutoffs for acoustic reflex thresholds (ARTs) were determined for a sample of 2,748 ears of 1,374 subjects with normal hearing and sensorineural loss of cochlear origin. All subjects had measurable hearing (less than or equal to 110 dB HL, ANSI-1969) at all three activator frequencies (500, 1000, and 2000 Hz). Cutoff values including "no responses" ("absent" reflexes at 125 dB HL) were higher than those excluding no responses when hearing losses were greater than about 55 dB. The 90th percentiles including the effects of no responses identified ears with retrocochlear involvement for hearing losses as great as about 756 dB. For greater hearing losses at the activator frequency, the no-response rate for both cochlear and retrocochlear cases is too high to enable them to be differentiated by acoustic reflex thresholds. The 90th percentiles are derived at each activator frequency collapsed across ears. It is therefore necessary to determine the probabilities that normal or cochlear-impaired ears will have one, two, or three frequencies at which the ARTs exceed their respective 90th percentiles. It was found that among normal and cochlear-impaired ears, 12.2% have one ART elevated above the 90th percentile, but only 5.6% have two or three elevated ARTs. Clinical implications are discussed. PMID- 2329785 TI - Black English in a Mississippi prison population. AB - Nine linguistic features unique to Black English were examined in the speech of 87 Black and 77 White inmates of a Mississippi prison population. The purpose of the study was to determine whether Black inmates could be distinguished from White inmates by their use of the present progressive, final stops, distributive be, remote aspect been, noun plurals, third person singular present tense, possessives, consonant clusters, and the copula. Results showed that use of eight of the nine features accurately predicted the ethnicity of the subjects. Only remote aspect been failed to identify ethnic differences. Identification of dialect variation among minority populations and more specifically among prison populations is an important step toward providing effective remediation programs. PMID- 2329786 TI - Acoustic characteristics of female tracheoesophageal speech. AB - An acoustical description of speech and voice produced by 10 female tracheoesophageal (TE) speakers is provided. In light of results from earlier descriptions based on male TE speakers, and based on t-test comparisons, the female speakers produced generally more perturbation in fundamental frequency. Potential factors affecting this increase were elapsed time since the laryngectomy and extent of the laryngectomy surgery. The data from this investigation, however, indicate that in oral reading the characteristics of TE speech, including F0, may be highly similar regardless of speaker gender. PMID- 2329787 TI - Acoustic validation of phonological knowledge and its relationship to treatment. AB - The speech of 4 phonologically disordered children with place and voicing errors affecting initial stop consonants was described through phonological and acoustic analyses. Productions of target voiced and voiceless alveolar and velar stops were transcribed and acoustically analyzed before and after treatment that was administered on a predetermined contrast. Three of the children produced significant, although largely imperceptible, differences in VOT for a given stop when it represented different adult stops. The presence of productive phonological knowledge, as inferred from acoustic data, facilitated rapid generalization of correct production of the treated contrast. In the absence of acoustically determined productive knowledge, a longer treatment period was necessary to achieve a lower level of production accuracy on the same treated contrast. Sources of speech sound errors for the 4 children were hypothesized by comparing the children's underlying representations determined from both acoustic and descriptive phonological data. PMID- 2329788 TI - Maternal recasts and other contingent replies to language-impaired children. AB - Mothers' recasts and other contingent replies to their children's utterances were examined in two groups of mother-child dyads. In one group there were 14 dyads that contained language-impaired children; in the other there were 14 dyads that contained non-language-impaired children. Results indicated that mothers' overall use of recasts, as well as other contingent replies, was highly similar for the two groups, except that complex recasts were used more often by the mothers of non-language-impaired children. Differences in discourse functions were also observed. Mothers of language-impaired children used recasts less often than mothers of non-language-impaired children to respond to, or request clarification of, their children's utterances. Further, they more often used such replies to serve the functions of information requests, assertion, or direction. Recasts were also found to vary in relation to observed differences in children's intelligibility and in contrasting patterns of dialogue initiation for the two kinds of dyads. PMID- 2329789 TI - Sources of variability contributing to test-retest differences in threshold-based articulation indices. AB - This study was conducted to obtain information on test-retest differences in Articulation Indices (AI) when a clinical threshold-based method is used to calculate AI. The AI was calculated using a nine-frequency-band method on 2 separate days for 209 ears. Standard deviations of test-retest differences were calculated. The standard deviations were greatest when the AI was near 50% and least when the AI was near 0% or 100%. The standard deviations for test-retest AI differences were also dependent on the relationship of the hearing thresholds and speech spectrum. Under the assumption that each dB change in threshold would have an affect on the AI, standard deviations of test-retest differences increased significantly. Test-retest standard deviations for nine-band and five-band methods were approximately equal when only five thresholds were actually measured. A small improvement would be expected if the number of threshold measurements increased from five to nine. PMID- 2329790 TI - Distinctive feature scoring of the California Consonant Test. AB - The purpose of this study was to evaluate a distinctive feature (DF) scoring technique for List 1 of the California Consonant Test (CCT) for the purpose of improving test reliability. The CCT was presented to 50 subjects with high frequency sensorineural hearing loss (HFSNHL). The DF scoring technique resulted in a split-half correlation of .86 compared to .78 for standard percentage correct scoring. A partial correlation of .50 was found for DF scoring with the effect of standard scoring held constant, indicating that DF scoring accounted for 25% of the variance in scores unaccounted for by standard scoring. DF scoring also led to smaller percentage differences between the two halves of the CCT (p less than .0005). An analysis of individual feature error patterns suggests that DF scoring may provide a more effective means of differentiating among listeners with HFSNHL than traditional scoring. PMID- 2329791 TI - An investigation into the relationship between anxiety and stuttering. AB - The relationship between self-reported anxiety and stuttering was explored. Although previous research has mostly shown that persons who stutter are no more anxious than persons who do not stutter, many of these studies had inadequate power to detect significant differences. In this study, a large number of stutters were assessed on state and trait anxiety before, and on trait anxiety after, intensive behavioral treatment. Their levels of anxiety were compared to those of nonstuttering controls matched for gender, age, and occupational status. Results showed that persons who stutter had significantly higher levels of fear (state anxiety) in a demanding speech situation. They were also shown to have higher levels of chronic anxiety (trait anxiety) than matched controls. However, trait anxiety measured after treatment was within normal levels. Although not allowing the conclusion that anxiety causes stuttering, these results do have important implications for the management of the disorder. PMID- 2329792 TI - Speech-related reaction times of stutterers and nonstutterers: diagnostic implications. AB - Speech-related reaction time measures (laryngeal premotor and adjustment time for /a/, labial initiation and physiological voice onset time for /pa/) and fluency related measures (number of stutterings, number of normal disfluencies, and time needed to complete an oral reading) of 24 stutterers and a like number of nonstutterers were assessed to determine their diagnostic discriminative power. Discriminant analysis showed that stutterers were most effectively differentiated from normally fluent speakers by the total number of stutterings and normal disfluencies during oral reading and by the duration of laryngeal adjustments prior to cued phonation. Factor analysis revealed that the fluency failure and reaction time measures clustered independently for both stutterers and nonstutterers. These findings suggest that both fluency failures and the duration of laryngeal adjustment time are useful diagnostic measures for discriminating stutterers from those who are normally fluent. PMID- 2329793 TI - The speech and language characteristics of children with Prader-Willi syndrome. AB - Prader-Willi syndrome was initially identified in 1956. Since then, a majority of the literature pertaining to Prader-Willi has focused on the medical and genetic aspects of the syndrome. There has been limited information available regarding the speech and language abilities of children with Prader-Willi. This study investigated the communicative development of 18 children with the syndrome, ranging in age from 8:8 to 17:1. A number of evaluative procedures were used to evaluate the subjects' spontaneous speech, articulation, and receptive and expressive language abilities, as well as their voice, fluency, oral mechanisms, hearing, and their developmental histories. A variety of communicative deficiencies were found in the children's speech, language, voice, and fluency. PMID- 2329794 TI - Comprehension of social-action games in prelinguistic children: levels of participation and effect of adult structure. AB - We currently lack a systematic approach to examine the emergence of social-action games during the prelinguistic period of development. Although social-action games have been identified as being an important part of prelinguistic development, a systematic approach to examine their emergence has been lacking. Further, research has yet to analyze how contextual variables affect a child's comprehension and participation during these action routines. Results of the present study document changes in the development of social-action games in 29 normally developing subjects from 9 to 15 months and support a developmental hierarchy of social-action game participation. The results also reflect the effect of adult structure on the subject's level of performance and reveal a significant relationship between adult contextual support and child performance. The implications of the findings are summarized. PMID- 2329795 TI - Parents' use of Signing Exact English: a descriptive analysis. AB - Parental use of simultaneous communication is advocated by many programs serving hearing-impaired students. The purpose of the present study was to describe in detail the input characteristics of five hearing parents, who were attempting to use one such system, Signing Exact English or SEE 2 (Gustason, Pfetzing, & Zawolkow, 1980). The parents were intermediate-level signers, motivated to use SEE 2. Voiced and signed segments from videotaped language samples were transcribed and coded for equivalence and other features of interest. Results were that parents' signed mean lengths of utterance (MLUs) were lower than those of their children although the majority of their sign utterances were syntactically intact. Structures categorized as complex in the Developmental Sentence Scoring procedure (Lee, 1974) and considered abstract in a semantic coding scheme (Lahey, 1988) were seldom used by the parents. Parents provided a narrow range of lexical items in their sign code. Results are discussed in terms of the type of input the parents are providing and the procedures used to identify priorties for parent education. PMID- 2329796 TI - Hyperacusis and otitis media in individuals with Williams syndrome. AB - Williams syndrome is characterized by cardiac defects, varying degrees of physical and developmental delay, stellate eye pattern, possible elevated serum calcium level, and elfin/pixie facial features. A problem perhaps unique to these children is hyperacusis that can be severe enough to disrupt many routine daily activities. Parental questionnaires were used to determine the prevalence of hyperacusis and otitis media in individuals with Williams syndrome. Prevalences of 95% for hyperacusis and 61% for otitis media were found. This was significantly higher than in the general population. Despite the prevalence of hyperacusis, parents of these children were not counseled about management of the problem. The audiologist may become involved with Williams syndrome patients through hearing assessment and management, parental counseling, and research. PMID- 2329797 TI - Perceptual characteristics of consonant production by apraxic speakers. AB - Single-word repetitions by 4 brain-damaged adults with apraxia of speech (AOS) but without concomitant aphasia were transcribed using a standard narrow phonetic transcription system. Analysis of consonant productions yielded a profile of AOS slightly different from the traditionally accepted one. Among the results was the atypical finding that consonant distortions exceeded all other error types including sound substitutions. In addition, errors predominated in the medial position of words, and monosyllabic words had approximately the same error rate per number of consonants as did multisyllabic words. Results are discussed with reference to previous perceptual descriptions of AOS and in relationship to Broca's aphasia. Results are also interpreted relative to linguistic and motoric components of speech production models. PMID- 2329798 TI - Consistency of fundamental frequency and perturbation in repeated phonations of sustained vowels, reading, and connected speech. AB - The purpose of this study was to determine consistency of the acoustic measurement of fundamental frequency (f0) and f0 perturbation using the Visi Pitch. Samples of speech including a reading passage, vowels, and spontaneous speech were recorded for 12 normal young adults (6 men and 6 women). The results indicated that test-retest reliability was highest for the reading passage. The measurements of fundamental frequency for reading and spontaneous speech were very similar, but vowel production was, on average, higher in frequency than the other contexts. Test-retest measures of perturbation using the Visi-Pitch did not have a high correlation coefficient. Perturbation measures must be interpreted cautiously because of the influence of frequency. PMID- 2329799 TI - Investigation of rat mast cell degranulation using flow cytometry. AB - Mast cells degranulation has been assessed by flow cytometry (FACS) taking advantage of the changes in the light scattering properties of mast cells stimulated by secretagogues. In turn, these changes are based on the modification of size, shape, and granule content of the cells before and after stimulation. With FACS, it is possible to work with almost pure mast cell populations (greater than 99%). Moreover, responses to compound 48/80 are carried out in real time and on the same cell sample that acts as internal control. This technique is very sensitive as shown by the ED50 of compound 48/80 (0.051 micrograms/mL) compared to its ED50 on histamine release (0.131 micrograms/mL). The well-known inhibitory effect of disodium cromoglycate against compound 48/80 was clearly observed using FACS. Furthermore, FACS allowed to distinguish between specific degranulating effects and cytotoxicity. Among the secretagogues used, only the degranulation induced by phospholipase A2 was inhibited by in vivo treatment with dexamethasone. It is suggested that the inhibitory effect is due to induction of phospholipase A2-inhibitory proteins (lipocortins). PMID- 2329800 TI - Very rapid and simple assay of taurine in the brain within two minutes by high performance liquid chromatography with electrochemical detection. AB - We describe a very rapid and simple method for the assay of taurine (Tau) in the brain tissue, using high-performance liquid chromatography (HPLC) with electrochemical detection in combination with precolumn o-phthalaldehyde (OPA) derivatization. The present method permits Tau assay within 2 min in one chromatographic run. Recovery for Tau was 107.4 +/- 1.3% (SD, n = 10). Within-run coefficients of variation were +/- 1.6% (n = 15). The limit of quantitative detection of the method was 0.1 pmol for Tau. The present method has been applied to the measurement of Tau levels in several discrete brain areas of the mouse. PMID- 2329801 TI - New spinal cord injury model produced by spinal cord compression in the rat. AB - Graded spinal cord injuries were produced in rats by compressing the spinal cord at the level of the T11 vertebra for 5, 15, 30, 60, or 180 min with stainless steel screws of 2-mm diameter and 2.8-mm length, or for 60 min with screws of the same diameter and various lengths (2.5, 2.8, 3.1, or 3.4 mm). The main neurologic symptoms caused by spinal cord compression were motor deficits, sensory deficits, and urinary incontinence. Neurologic scores, based on both motor and sensory deficits, correlated significantly with both the screw length and the duration of compression at every observation point from 4 hr to 21 days after removal of the screw. The incidence of urinary incontinence (from 24 hr to 21 days) and the percentage of rats surviving (from 14 days to 21 days) also correlated closely with the two factors (screw length and duration of compression). These results suggest that the present procedure could be a useful and simple model for studying traumatic spinal cord injury in rats. PMID- 2329802 TI - Use of the ferret for a myocardial ischemia/salvage model. AB - Exploratory work was undertaken in the anesthetized ferret to determine if it is an applicable species for use as an in vivo ischemic model and suitable for recovery surgical procedures. Experimental protocols utilizing varying combinations of left anterior descending (LAD) coronary artery occlusion (30, 60, 90 min) and reperfusion (4, 6, 18-24 hr) were evaluated. The results indicated that a 90-min/6-hr combination led to the production of an infarct equivalent, or slightly greater, in size to that observed following coronary artery occlusion either with and without reflow during an 18-24-hr recovery period prior to sacrifice. A combination of 90 min occlusion/4 hr reperfusion yielded an infarct area ca. 50% of that associated with 6 hr interval of reflow. An occlusive interval of 60 min or less combined with any reperfusion interval lack reproducibility. The administration of saline in varying volumes by different routes (IV versus left atrial) had no influence on either the absolute or, more especially, the relative (i.e., as a percent of left ventricle) tissue damage provoked by a 90-min/6-hr occlusion/reperfusion maneuver of the LAD coronary artery. When evaluated as a reference standard, superoxide dismutase (SOD) infused via the left atrium at a dose of 5 mg/kg afforded a 36% reduction in the area of ischemic damage in this model. These studies demonstrated that the ferret represents a useful species for initial, rapid, and economic--both in terms of cost and drug substance utilization--in vivo myocardial salvage screening assessments. The model permits an interpretation of potential test agent efficacy, dosage requirements, and hemodynamic actions, and it is suitable for basing a go/no-go decision that continued experimental development in more labor intense preparations is warranted. PMID- 2329803 TI - Estimation of agonist affinity and efficacy by direct, operational model-fitting. AB - A few years ago Black and Leff (1983) presented a theoretical model for agonist action that can be fitted directly to experimental agonist concentration-effect data in order to estimate affinities and relative efficacies of agonists. The model has been successfully applied to data obtained using experimental designs commonly employed in pharmacologic experiments. This article describes the methodology used to fit the model equations to data for full and partial agonists, shows how affinity and efficacy estimates are calculated for these values, and shows how experimental design influences these calculations. PMID- 2329804 TI - Preliminary psychopharmacological evaluation of Ocimum sanctum leaf extract. AB - An ethanol extract of the leaves of Ocimum sanctum was screened for its effects on the central nervous system. It prolonged the time of lost reflex in mice due to pentobarbital, decreased the recovery time and severity of electroshock- and pentylenetetrazole-induced convulsions, and decreased apomorphine-induced fighting time and ambulation in "open field" studies. Using a behavioural despair model involving forced swimming in rats and mice, the extract lowered immobility in a manner comparable to imipramine. This action was blocked by haloperidol and sulpiride, indicating a possible action involving dopaminergic neurones. In similar studies, there was a synergistic action when the extract was combined with bromocriptine, a potent D2-receptor agonist. PMID- 2329805 TI - Screening of Icacina trichantha extracts for pharmacological activity. AB - Some preliminary studies were conducted on the biological activities of Icacina trichantha in mice. In vitro tests performed with the 70% ethanol, petroleum ether and aqueous extracts of tubers, roots, stems and leaves did not show contraction of isolated guinea pig ileum up to a bath concentration of 40.5 mg/ml. Graded oral doses (100, 200, 400 and 800 mg/kg) of the aqueous extract of tubers produced wet faeces in mice with the number of wet faeces increasing with increasing dose up to 400 mg/kg. A time-course study of the purgative effect showed the maximum purgative response to be 7-8 h after oral dosing. The aqueous extract of tubers significantly potentiated pentobarbital-induced loss of righting reflex at a dose of 80 mg/kg i.p. but this dose did not protect mice from strychnine or leptazole convulsions and death. PMID- 2329807 TI - Paraguayan medicinal compositae. AB - A survey of the Compositae used in traditional medicine and as economic plants by Paraguayan country people was undertaken to identify the components of crude drugs traded by herbalists. Forty-five medicinal and economic species have been identified through field work in the rural areas and enquiries in the markets, as well as by examination of the literature in the Spanish language. Some crude drugs are shown to be mixtures of several closely-related species. The role of indigenous plant remedies within the local health care system is also discussed. PMID- 2329806 TI - Preliminary toxicity studies on ethanol extracts of the aerial parts of Artemisia abyssinica and A. Inculta in mice. AB - Ethanolic extracts of the aerial parts of Artemisia abyssinica and A. inculta were subjected to acute toxicity observations in mice for 24 h and chronic toxicity evaluation for 3 months. External morphological changes, visceral toxicity, haematological changes, spermatogenic dysfunction and effect on body weight and vital organ weight were recorded. In both the chronically treated groups, no significant acute mortality was observed up to 3 g/kg p.o. There was no weight gain in A. abyssinica chronically-treated mice while the weight gain of A. inculta-treated animals matched that of the control group. Significant sperm damage was observed in A. abyssinica-treated mice while A. inculta failed to produce any significant spermatotoxic effect. PMID- 2329808 TI - Post-testicular antifertility effects of Abrus precatorius seed extract in albino rats. AB - Oral administration of a 50% ethanol extract of Abrus precatorius seeds (250 mg/kg) in albino rats for 30 and 60 days induced an absolute infertility in males which was reversible. Suppression of sperm motility in the cauda epididymis was the most pronounced effect of the treatment. Such treatment may affect the oxidative/energy metabolism of the cauda epididymis. Histological and histocytometric observations in testis and parareproductive tissues appeared normal while the protein, sialic acid, acid phosphatase and succinic dehydrogenase levels were significantly depleted. PMID- 2329809 TI - Changes in sensitivity of the isolated guinea-pig vas deferens induced by a lyophilized Phoradendron latifolium leaf infusion. AB - The effect of a lyophilized mistletoe infusion (LMI) was studied on isolated guinea-pig vas deferens. LMI caused a contraction which was partially blocked by phentolamine but not by atropine. LMI caused a shift to the left of the norepinephrine concentration-effect curve (CEC), an effect which appeared to be blocked by atropine and was absent in animals previously treated with reserpine and alpha-methyl-para-tyrosine. The increase of the norepinephrine maximal response induced by LMI was not blocked by atropine or pharmacological denervation. LMI caused a shift to the right of the acetylcholine CEC and had no effect on the acetylcholine maximal response. These results suggest that the effects seem to be due mainly to the presence of potassium ion in the LMI; however, the participation of muscarinic agonist(s) of reduced intrinsic activity or some tyramine-like substance could not be ruled out. PMID- 2329810 TI - Ethnobotanical inventory of medicinal plants used by the Guaymi Indians in western Panama. Part II. AB - A list of newly identified plants is presented to supplement Part I (Joly et al. (1987) Journal of Ethnopharmacology 20, 145-171). A comparative analysis is made between our work and two other recent inventories of plants used by the Guaymi Indians of Panama and Costa Rica. As in Part I, the results of a literature survey are also provided, including medicinal uses, known constituents and pharmacological effects. PMID- 2329811 TI - Analgesic activity of certain flavone derivatives: a structure-activity study. AB - Flavone and 10 hydroxy and glucoside flavone derivatives were synthesised. They were tested for their analgesic effect in mice employing acetic acid-induced writhing and tail immersion methods. Subcutaneously all the tested compounds exhibited significant analgesic activity with varying potencies in both assay models. The activity of flavone and its 5-; 7-; 2'-; 5,7- and 7,8-hydroxy derivatives apparently involves an opiate-like mechanism, since their activity was reversed by naloxone pretreatment. It is suggested that flavonoid substances may utilise more than one mechanism in eliciting analgesia. PMID- 2329812 TI - Rat toxicity studies with beta-sitosterol. AB - Chronic administration of beta-sitosterol subcutaneously to rats for 60 days was well tolerated and there was no clear cut evidence of any gross or microscopic lesions either in the liver or kidney. Liver and kidney function tests were assessed by determining the blood/serum parameters like haemoglobin, blood glucose, serum protein, serum bilirubin, serum cholesterol, serum GPT and serum GOT. All the parameters were in the normal range except serum protein and serum cholesterol. Serum cholesterol was the only variable which depleted markedly in both sexes in a dose-dependent manner suggesting intrinsic hypocholesterolemic effect of the sterol. PMID- 2329813 TI - Pharmacokinetics of the total triterpenic fraction of Centella asiatica after single and multiple administrations to healthy volunteers. A new assay for asiatic acid. AB - A new HPLC assay method was used to investigate the pharmacokinetics of asiatic acid after oral administration of the total triterpenic fraction of Centella asiatica in single doses (30 or 60 mg) and after a 7-day treatment (30 or 60 mg twice daily). Twelve healthy volunteers received each treatment following a randomized cross-over design with trials separated by a 3-week interval. The time of peak plasma concentration was not affected by dosage difference or by treatment scheme. Differences in peak plasma concentration and area under the concentration vs. time curve from 0 to 24 h (AUC0-24) calculated after 30 or 60 mg administration (single dose) were accounted for by the different dose regimen. However, after chronic treatment with both 30 and 60 mg, peak plasma concentrations, AUC0-24 and half-life were significantly higher than those observed after the corresponding single dose administration. This phenomenon could be explained by a metabolic interaction between asiatic acid and asiaticoside, which is transformed into asiatic acid in vivo. PMID- 2329814 TI - Lesser-known herbal remedies as sold in the market at Murcia and Cartagena Spain. PMID- 2329815 TI - Multiple primary lung cancers. Results of surgical treatment. AB - During a 13-year period, multiple primary lung cancers were diagnosed in 80 consecutive patients. Forty-four patients had metachronous cancers. The initial pulmonary resection was lobectomy in 36 patients, bilobectomy in 3, pneumonectomy in 1, and wedge excision or segmentectomy in 4. The second pulmonary resection was lobectomy in 16 patients, bilobectomy in 2, completion pneumonectomy in 7, and wedge excision or segmentectomy in 19. There were two 30-day operative deaths (mortality rate, 4.5%). Actuarial 5- and 10-year survival rates after the first pulmonary resection for stage I disease were 55.2% and 27.0%, respectively. Five year and 10-year survival rates for stage I disease after the second pulmonary resection were 41.0% and 31.5%, respectively. The remaining 36 patients had synchronous cancers. The pulmonary resection was lobectomy in 18 patients, bilobectomy in 3, pneumonectomy in 10, and wedge excision or segmentectomy in 8. There were two 30-day operative deaths (mortality rate, 5.6%). Actuarial overall 5- and 10-year survival rates after pulmonary resection were 15.7% and 13.8%, respectively. We conclude that an aggressive surgical approach is safe and warranted in most patients with multiple primary lung cancers and that the presence of synchronous primary cancers is ominous. PMID- 2329816 TI - Resection of tracheal carina for lung cancer. Procedure, complications, and mortality. AB - We studied 20 patients with lung cancer that invaded the tracheal carina who were operated on during a recent 12-year period. Fifteen patients underwent sleeve pneumonectomy, two had pneumonectomy, one had lobectomy with wedge resection of the carina, and two patients had sleeve resection of the carina followed by reconstruction of the carina. There were two patients with postsurgical stage IIIA lung cancer, 15 with stage IIIB, and three with stage IV disease that involved intrapulmonary metastases. However, the operations of 13 patients were curative resections in which the surgical margin was negative for disease. Sleeve pneumonectomy was performed only in the last 3 years of the study period, after we had confirmed the safety and good results of bronchoplastic surgery by our experience of 100 cases of sleeve lobectomy. Hence, the period of follow-up in this group is too short to assess long-term survival. Eleven patients are alive, three died within 1 month after operation (15%), three died in the hospital beyond 1 month after the operation, and three died after discharge from hospital. Nine of the 11 surviving patients have no evidence of disease 1 month to 2 1/2 years after the operation, but two are alive with supraclavicular lymph node metastases. The 1-year and 2-year survival rates for 17 cases (excluding the three operative deaths) were both 59% by the Kaplan-Meier method. Two different methods were used to adjust the difference of calibers of the trachea and the bronchus. The first method involved the shift of the edge of the cartilagonous portion of the bronchus against the edge of the cartilaginous portion of the trachea and the other involved cutting the tracheal wall as a wedge-shaped piece to shorten the diameter of the tracheal caliber. To prevent complications after resection of the tracheal carina in 11 recent cases with sleeve pneumonectomy, anastomoses were protected by a pedicle fat flap nourished by internal thoracic artery and vein. No postoperative complications of anastomoses developed in any of these cases. PMID- 2329817 TI - Surgical treatment for infarct-related ventricular septal defects. Improved early results combined with analysis of late functional status. AB - A total of 101 patients (mean age 64.9 years) underwent surgical correction of postinfarction ventricular septal defect at this institution over a 15-year period (1973 to 1988). The overall early mortality rate was 20.8%, although the most recent experience with 36 patients (January 1987 to October 1988) has seen this decline to 11.1%. Factors found to influence early death significantly, when analyzed univariately, were as follows: (1) site of infarction (anterior 12.1%, inferior 32.6%, p = 0.02); (2) time interval between infarction and operation (less than 1 week 34.1%, greater than 1 week 10.5%, p = 0.008); (3) cardiogenic shock (present 38.1%, absent 8.5%, p = 0.001). Nonsignificant variables included preoperative renal function, age, and concomitant coronary artery bypass, although older age (greater than 65 years) became significant when examined in a multivariate fashion. Of the 80 hospital survivors, eight were subsequently found to have a recurrent or residual defect necessitating reoperation, with survival in seven. Late follow-up is 99% complete and reveals an actuarial survival rate for 100 patients of 71.1% at 5 years (95% confidence interval 60.6 to 80.0), and 40.0% at 10 years (95% confidence interval 21.7 to 58.4). A significant recent change in policy of not using coronary angiography in patients with a ventricular septal defect caused by anterior wall infarction has not resulted in any increase in either the early mortality or in the late prevalence of angina. The functional status of 38 surviving patients has been analyzed by a graded treadmill exercise protocol, whereas left ventricular functional assessment was by nuclear scan with additional information on mitral valve function by echocardiogram. Color Doppler flow mapping has been used to determine the presence of a residual defect. Most late survivors have limited exercise tolerance related to both cardiac and noncardiac factors. Left ventricular function is moderately impaired (mean ejection fraction = 0.39). However, many patients are elderly and have adapted to their residual symptoms without significant changes in life-style. PMID- 2329818 TI - Effects of the left ventricular assist device on right ventricular function. AB - Right ventricular failure is a leading cause of death in patients who require the left ventricular assist device. Previous reports suggested right ventricular functional deterioration during left ventricular assist but lacked a method by which right ventricular function could be quantified adequately. This study examined the effects of left ventricular volume unloading on right ventricular systolic function by means of the stroke work/end-diastolic volume relationship, a load-insensitive index of myocardial performance. In 12 anesthetized open chested dogs, right ventricular and left ventricular pressures were measured with micromanometers while ultrasonic dimension transducers measured left and right ventricular orthogonal diameters. Left ventricular unloading was accomplished with left atrial-to-femoral artery bypass with a centrifugal pump. Data were recorded during transient vena caval occlusion in the control state and with maximal left ventricular unloading by full support by the left ventricular assist device. Modified ellipsoidal geometry was used to calculate simultaneous biventricular volumes, and linear regression analysis of right ventricular stroke work versus end-diastolic volume was used to quantify right ventricular systolic function. Average slope and x intercept of this relationship under control conditions were 2.2 +/- 0.3 X 10(4) erg/ml and 10.7 +/- 5.0 ml, respectively. During full support by the left ventricular assist device (mean flow rate, 2.4 +/ 0.3 L/min), left ventricular end-diastolic volume decreased by 31% (p less than 0.01), left ventricular septal-free wall diameter decreased by 7% (p less than 0.001), and rate of rise of right ventricular peak positive pressure declined by 13% (p less than 0.05). The corresponding slope and x intercept of the right ventricular stroke work/end-diastolic volume relationship during full unloading of left ventricular assist device were 2.3 +/- 0.3 X 0.3 X 10(4) erg/ml and 14.3 +/- 4.8 ml, respectively; these values were not significantly different from control values (p greater than 0.5). Additionally, analysis of right ventricular end-diastolic pressure-volume relationships suggested improved right ventricular chamber compliance, although the effects were small and did not reach statistical significance (p = 0.10). These data imply that marked alterations in biventricular geometry accompanying left ventricular volume unloading by the left ventricular assist device in a normal heart do not significantly alter right ventricular performance characteristics. PMID- 2329819 TI - Latissimus dorsi dynamic cardiomyoplasty of the right ventricle. Potential for use as a partial myocardial substitute. AB - Full-thickness right ventricular latissimus dorsi dynamic cardiomyoplasty with the Medtronic Cardiomyostimulator (Medtronic, Inc., Minneapolis, Minn.) was performed in a chronic canine model. In one group (n = 2) the latissimus dorsi was electrically preconditioned before cardiomyoplasty. In a second group (n = 3) cardiomyoplasty was performed and the muscle was progressively stimulated, with conditioning accomplished while the latissimus dorsi was functioning on the ventricle. The contribution of the stimulated latissimus dorsi to global ventricular function was assessed, and the effects of varying muscle stimulation parameters on latissimus dorsi function and hemodynamics were examined. Right ventricular systolic pressure increased 8%, from 23.2 +/- 0.95 to 25.1 +/- 1.5 mm Hg. The rate of pressure rise increased 37% from 226 +/- 13 to 309 +/- 12 mm Hg/sec. Right ventricular ejection fraction was measured in two dogs and increased 29% with latissimus dorsi stimulation, from 51.5% +/- 13.5% to 66.5% +/ 14.5%. Although the sample size was small, there was no difference observed between the preconditioned and nonpreconditioned groups. Right ventricular systolic pressure, rate of pressure rise, and percent latissimus dorsi fiber shortening increased as voltage and burst frequency of the muscle stimulus increased, whereas increasing the burst duration had little effect in two dogs so studied. Latissimus dorsi dynamic cardiomyoplasty can function as a partial myocardial replacement in a chronic canine model, apparently without preconditioning of the muscle. The degree of cardiac assist obtained with cardiomyoplasty appears to be influenced by the voltage and frequency of the stimulus applied to the muscle. Although it is unclear whether these results can be extrapolated to the left ventricle, this technique may find application in the treatment of ventricular aneurysm or ventricular tumor. PMID- 2329820 TI - Comparative assessment of chordal preservation versus chordal resection during mitral valve replacement. AB - Left ventricular function often deteriorates after mitral valve replacement for mitral regurgitation. It has been postulated that disruption of the mitral valve apparatus at operation is a major mechanism of postoperative dysfunction. The hypothesis tested in this investigation was that chordal preservation results in more favorable left ventricular function. Sixty-nine patients with isolated mitral regurgitation who underwent mitral valve replacement were studied before and 6 months after operation by treadmill exercise testing, catheterization, echocardiography, and radionuclide angiography. Nine patients underwent mitral valve replacement with preservation of the entire mitral apparatus and five with preservation of the posterior leaflet and attached chordae. The remaining 55 had mitral valve replacement with complete excision of the native valve. Preoperatively, there were no differences among groups in age, gender, exercise capacity, cardiac index, rest or exercise ejection fraction, fractional shortening, or pulmonary artery pressures. There were four perioperative deaths (7%) and eight late deaths among the 55 patients with chordal resection but no early or late deaths of patients whose chordae were preserved (p = 0.05). In patients in whom the chordae were excised, exercise capacity, left ventricular systolic dimensions, and cardiac index did not improve after mitral valve replacement, and left ventricular function deteriorated, as evidenced by a reduction of both the resting and exercise ejection fractions (from 46% +/- 13% to 31% +/- 13%, p = 0.0001, and from 49% +/- 12% to 37% +/- 14%, p = 0.0007, respectively) and fractional shortening (from 34% +/- 10% to 26% +/- 14%, p = 0.0001). In contrast, exercise capacity improved after mitral valve replacement in patients in whom the entire apparatus was spared (by 4 +/- 3 minutes, p = 0.05), left ventricular systolic dimensions decreased (from 44 +/- 8 to 36 +/- 9 mm, p = 0.03), and left ventricular function was maintained or improved, as evidenced by preservation of the resting ejection fraction (preoperative, 50% +/- 14%; postoperative, 54% +/- 11%; p = no significant difference), exercise ejection fraction (46% +/- 16% versus 52% +/- 9%, p = no significant difference), fractional shortening (from 31% +/- 9% to 28% +/- 9%, p = no significant difference), and an increase in the cardiac index (from 2.0 +/- 0.3 to 2.7 +/- 0.5 L/min/m2, p = 0.05). No statistically significant differences between posterior chordal resection only and preservation of the entire apparatus were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329821 TI - Long-term performance of the Hancock porcine bioprosthesis in the tricuspid position. A review of forty-five patients with fourteen-year follow-up. AB - Because little information is available regarding the clinical performance of the Hancock porcine bioprosthesis (Johnson & Johnson Cardiovascular, King of Prussia, Pa.) implanted in the tricuspid position, we reviewed the long-term follow-up of patients who had tricuspid valve replacement with this device. From March 1970 to December 1983, 45 patients had tricuspid valve replacement, either isolated (seven patients) or combined with replacement of other valves (38 patients) by means of a standard, glutaraldehyde-preserved Hancock porcine bioprosthesis. Follow-up ranged from 0.2 to 14.7 years (mean, 7.6 +/- 3.6 years) and was complete. The late mortality rate was 6.6% +/- 1.6%/pt-yr and the actuarial survival rate at 14 years was 23% +/- 9%. Reoperation because of structural deterioration of the tricuspid, the mitral, or both bioprostheses was performed in nine patients (3.7% +/- 1.2%/pt-yr) from 40 to 177 months (mean, 112 +/- 43 months) and resulted in no deaths. Actuarial freedom from structural deterioration of a Hancock tricuspid porcine bioprosthesis at 14 years is 68% +/- 13%. Morphologic examination of explanted porcine bioprostheses showed that those implanted in the tricuspid position had lower degrees of calcification and less severe structural changes than those simultaneously explanted from the mitral position. We conclude that the Hancock porcine bioprosthesis has an acceptable long-term durability and satisfactory performance after tricuspid valve replacement, and we continue to favor its use in the tricuspid position even in association with mechanical prostheses in the left side of the heart. PMID- 2329822 TI - Selective annuloplasty of the tricuspid valve. Two-year experience. AB - Between July 1986 and March 1989, 48 patients whose ages averaged 60 +/- 6 years were subjected to a new technique for tricuspid valve annuloplasty. The preoperative New York Heart Association functional class averaged 3.7. There were 32 mitral-tricuspid procedures, 13 aortic-mitral-tricuspid procedures, and three repeat tricuspid annuloplasties. The hospital mortality rate was 6.3% with three deaths resulting from cardiac or respiratory failure, or both. Follow-up averaged 14 +/- 8 months. One patient (2.2%) died suddenly, 7 months postoperatively. All patients whose follow-up period lasted 6 months or more improved to class I or II. Twenty-six patients were reinvestigated by catheter or echocardiographic methods, or both. The gradient over the tricuspid valve averaged 1.4 +/- 0.6 mm Hg, and a moderate regurgitant murmur (2/3) was detected in four cases. The diameter of the tricuspidal anulus in the apical four-chamber view decreased from 23.7 +/- 3.9 mm/m2 body surface area preoperatively to 15.7 +/- 1.9 mm/m2 body surface area at late follow-up examination. The present technique allows an anatomic and functional reconstruction of the tricuspid valve with a good compromise between stenosis and regurgitation. The overall mortality rate is low and functional improvement is striking. PMID- 2329824 TI - Hemorrhagic infarction of hilar lymph nodes associated with combined heart-lung transplantation. AB - The histologic changes in lymph nodes transplanted during combined heart-lung transplantation were examined. We studied at autopsy nine patients who had received a total of 10 heart-lung transplants. Hemorrhagic infarction of hilar nodes was found in eight of the 10 transplanted lungs. Pulmonary parenchymal pathologic changes associated with lymph node infarction included acute rejection (two cases), chronic rejection with bronchiolitis obliterans (two cases), and pneumonia (four cases). In one of the transplants without lymph node infarction there was chronic rejection with bronchiolitis obliterans and in another there was evidence of bronchopneumonia. The hemorrhagic lymph node infarction seen in the recipients of combined heart-lung transplant's may be directly attributable to the interruption of bronchial arteries and veins by the surgical procedure. At present the possible contribution of node infarction to postoperative morbidity or mortality is unknown. PMID- 2329823 TI - Rabbit antithymocyte globulin. A 10-year experience in cardiac transplantation. AB - Rabbit antithymocyte globulin, a "custom-made" pan-anti-T-cell antibody produced in rabbits, is currently being evaluated in the United States and may, within several years, become approved by the Food and Drug Administration. Because we have used this agent for induction of immunosuppression for 10 years in cardiac recipients and because the results appear to be more favorable than those obtained with other agents (horse antithymocyte globulin, antilymphocyte globulin, OKT3), we have reviewed our experience. For the purpose of analysis, all non-bridge-to-transplant cardiac recipients have been divided into three groups on the basis of immunosuppression protocol: group I (March 1979 to January 1983), 28 patients treated with rabbit antithymocyte globulin, steroids, and azathioprine; group II (January 1983 to March 1985), 29 patients treated with rabbit antithymocyte globulin, cyclosporine, and steroids; and group III (March 1985 to January 1989), 98 patients treated with rabbit antithymocyte globulin, cyclosporine, steroids, and azathioprine. Actuarial data showed advantage for group III in survival rate (1 year 94%, 2 years 91%, 3 years 88%), freedom from rejection (30% free at 1 year), freedom from infection (50% free at 1 year), freedom from death from rejection (99% free at 1 year), and freedom from death from infection (97% freedom at 1 year). Actuarial survival rates and freedom from death from rejection and infection are comparable for any of our groups with contemporary published data. In the past 3 years, we have had no death from acute rejection or from posttransplant infection. Time-related rates of infection by etiologic agents have shown a significant reduction in early bacterial, viral, and nocardial infections between groups I and III. With rabbit antithymocyte globulin 200 mg intramuscularly every day for 3 days, our current protocol, T cells are significantly reduced and local and systemic toxicity is almost unnoticeable. A progressively increasing cyclosporine dose along with rapid tapering steroid and maintenance azathioprine immunosuppressive induction appears to be the therapy of choice in cardiac transplantation. PMID- 2329825 TI - Quality control of perfusion: monitoring venous blood oxygen tension to prevent hypoxic acidosis. AB - The long-held belief that venous oxygen tension mirrored tissue oxygen tension became suspect in the 1960s when new instrumentation consistently showed that tissue oxygen tension was 10 to 30 torr less than venous oxygen tension. Moreover, a countercurrent of oxygen exchange between terminal arteries and veins was shown to exist. Despite this conflict in scientific theory, however, monitoring venous oxygen tension as a means to control hypothermic cardiopulmonary bypass has been repeatedly urged, since myocardial acidosis is clearly extremely detrimental. This study of the relationship between venous oxygen tension during hypothermic bypass and a concurrent increment in lactacidemia yields strong objective evidence to support the use of on-line venous oxygen tension monitoring to guide perfusion. In a random series of 36 patients, venous blood samples were drawn at five preselected intervals during operation and were analyzed for pH, carbon dioxide tension, oxygen tension, lactic acid, hematocrit, and base excess. Analysis of the data revealed that venous pH and base excess showed no correlation to venous oxygen tension. However, lactic acid showed a strong correlation with venous oxygen tension, with a correlation coefficient of 0.4338 at a confidence level of p less than 0.0001. If the patients were divided into three clinically pertinent groups based on the lowest venous oxygen tension recorded, a strong relationship between venous oxygen tension and lactic acid emerged. If the lowest measurement of venous oxygen tension was greater than 35 mm Hg (group A), the mean rise in lactic acid was only 0.12 microns/ml. If the lowest measurement was between 30 and 34 mm Hg (group B), the mean rise was 0.64 microns/ml. Whereas, if any venous oxygen tension value fell below 30 mm Hg (group C), the mean rise in lactic acid was 2.56 microns/ml. Analysis of variance showed that group C values were significantly different from groups A and B values (p less than 0.0002). A scientific hypothesis relating venous oxygen tension to adequate tissue oxygenation is proposed. Use of venous oxygen tension monitoring with the goal to maintain the level above 35 mm Hg is strongly supported by this study. PMID- 2329826 TI - Leukocyte depletion ameliorates free radical-mediated lung injury after cardiopulmonary bypass. AB - Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of lung injury associated with cardiopulmonary bypass. To determine whether leukocyte depletion could prevent this injury, we used a dog model simulating routine cardiac operations. Mongrel dogs (11 to 17 kg) were subjected to cardiopulmonary bypass with a bubble oxygenator and cooled to 27 degrees C. After aortic crossclamping and cardioplegic arrest for 90 minutes, control animals (n = 5) were rewarmed and weaned from bypass, and their condition was then stabilized for 90 minutes. Leukocyte-depleted animals (n = 5) had a leukocyte filter incorporated in the bypass circuit. During bypass, circulating leukocyte counts decreased by 60% in control dogs, and by 97% in leukocyte depleted animals. Free radical generation (estimated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by leukocyte depletion during and after bypass. Total hemolytic complement activity and the titer of C5 decreased markedly immediately after the onset of bypass in both the control and leukocyte-depleted animals. Pulmonary function after bypass was better preserved in leukocyte-depleted animals. These data suggest that depletion of circulating leukocytes contributes to lung injury during cardiopulmonary bypass and is associated with increased oxygen radical activity, pulmonary edema, and vasoconstriction. Leukocyte depletion substantially reduced the pulmonary injury seen after cardiopulmonary bypass. PMID- 2329827 TI - Intermittent hypothermic asanguineous cerebral perfusion (cerebroplegia) protects the brain during prolonged circulatory arrest. A phosphorus 31 nuclear magnetic resonance study. AB - A system has been developed for the nuclear magnetic resonance spectroscopic evaluation of cerebral high-energy phosphate levels during hypothermic total circulatory arrest and reperfusion by means of cardiopulmonary bypass in large animals. The use of intermittent hypothermic asanguineous cerebral perfusion, termed cerebroplegia, for the preservation of cerebral high-energy phosphates during a 2-hour period of hypothermic total circulatory arrest and reperfusion has been evaluated. Cardiopulmonary bypass was used to achieve deep hypothermia (12 degrees to 15 degrees C) during 2 hours of circulatory arrest and reperfusion. Juvenile sheep were divided into two groups. Group 1 animals (n = 8) (no cerebroplegia) served as the control group. In group 2 animals (n = 7), cerebroplegia was established by intermittent bilateral carotid artery infusion of a hypothermic oxygenated asanguineous cardioplegic solution. Nuclear magnetic resonance spectroscopy recorded changes in cerebral adenosine triphosphate, creatine phosphate, and intracellular pH. Adenosine triphosphate, creatine phosphate, and pH were higher in the group 2 animals for all points during the arrest period and until 60 minutes after reperfusion (p less than 0.05). Electroencephalographic activity returned after 36 minutes of reperfusion in group 2, but it did not return until 117 minutes in group 1 (p less than 0.05). In summary, cerebral high-energy phosphates and pH were maintained and the electroencephalographic signal returned more rapidly during circulatory arrest with the institution of cerebroplegia. These studies suggest that cerebroplegia is protective of the brain during circulatory arrest. PMID- 2329828 TI - Bypass of superior vena cava. Fifteen years' experience with spiral vein graft for obstruction of superior vena cava caused by benign disease. AB - Nine patients had operations for obstruction of the superior vena cava with superior vena caval syndrome caused by benign disease. Three patients had fibrosing mediastinitis, four had fibrosing mediastinitis with caseous necrosis, one had thrombosis of the superior vena cava around a pacemaker electrode, and one had spontaneous thrombosis of the superior vena cava. Patients ranged in age from 25 to 68 years. All bypass operations were performed with a composite spiral vein graft constructed from the patient's own saphenous vein, split longitudinally and wrapped around a stent in spiral fashion. The edges of the vein were sutured together to form a large conduit ranging in diameter from 9.5 to 15.0 mm. Six grafts were from the left innominate vein and three grafts were from the internal jugular vein. The grafts were placed into the right atrial appendage in all except one case, in which the graft was to the distal superior vena cava. Follow-up extends from 1 to 15 years. One patient required reoperation at 4 days for thrombosis at the innominate vein-graft anastomosis. Resection of the anastomosis and reconstruction of the graft rendered the patient symptom free. Two grafts closed during the first year after operation. One patient had advancing fibrosing mediastinitis, and a second bypass graft from the external jugular veins remain patent. Another patient had recurrence of spontaneous venous thrombosis. Thus seven of nine grafts remain patent for up to nearly 15 years and all but one patient is free of superior vena caval syndrome. These data show that bypass of the obstructed superior vena cava with a spiral vein graft relieves superior vena caval syndrome and demonstrate long-term patency of the graft. PMID- 2329829 TI - Surgical implications of juxtaposition of the atrial appendages. A review of forty-nine autopsied hearts. AB - We studied 49 hearts with juxtaposition of the atrial appendages, concentrating on the associated malformations and features of operative importance. Left juxtaposition was found in 42 cases (86%) and right juxtaposition in seven cases (14%). In the group of hearts with right juxtaposition, a normal segmental arrangement was present in three cases, double inlet in two cases, and double outlet right ventricle in the remaining two cases. Hearts with left juxtaposition had usual atrial arrangement with concordant atrioventricular connection, together with anomalous ventriculoarterial connection in 22 cases and univentricular atrioventricular connection in 19 cases. Only one specimen had a normal segmental arrangement. A partial form of left juxtaposition was present in 60% of the specimens. Hearts with left juxtaposition had a transverse orientation of the atrial septum, which was displaced posteriorly and inferiorly in the medial atrial wall, separated from the orifice of the juxtaposed appendage by a muscular band. A small right atrial chamber was noted in hearts with anomalous ventriculoarterial connection, creating the potential for anatomic difficulties during operation conducted within the atria. In two thirds of the cases with classic tricuspid atresia, the size of the orifice of the juxtaposed appendage was larger than the atrial septal defect, and an anastomosis of the appendage with the pulmonary trunk was morphologically feasible. PMID- 2329830 TI - Exit block in pediatric cardiac pacing. Comparison of the suture-type and fishhook epicardial electrodes. AB - Ninety-seven consecutive permanent epicardial pacemaker implantations were performed with either suture-type (group I, n = 52) or fishhook electrodes (group II, n = 45). In addition to epicardial fixation of the electrodes at the collar area, the suture-type was further secured in place by tying the electrode's suture at its exit to another nonabsorbable pledget-supported suture. Acute thresholds and slew rates were not significantly different between the two groups. Although the R wave was lower in group I (8.4 +/- 3.5 mV) than in group II (11.8 +/- 6, p less than 0.01), no sensing problems occurred. The larger surface area of suture-type electrode led to lower resistance in group I (271 +/- 61 omega) compared with group II (356 +/- 72, p less than 0.001); however, the difference in pacemaker generator longevity did not appear significant (group I, n = 12, mean 4.7 +/- 1.6 years; group II, n = 4, mean 5 +/- 0.6 years). The incidence of exit block was significantly higher in group II (40%, 18/45) than in group I (8%, 4/52, p less than 0.01). The length of the stimulation tip and better fixation of the suture-type electrode probably accounted for the observed difference in the incidence of exit block between the two electrodes. PMID- 2329831 TI - Effects of temperature on myocardial calcium homeostasis and mitochondrial function during ischemia and reperfusion. AB - An isolated rabbit heart preparation was used to characterize the effects of hypothermia on the deterioration in mitochondrial respiratory function and on the calcium overload that occurs during ischemia and reperfusion. Hearts were perfused aerobically with an asanguineous solution for 120 minutes or made totally ischemic for 90 minutes at 37 degrees, 34 degrees, 28 degrees, 22 degrees C, respectively, and reperfused for 30 minutes at 37 degrees C. Mitochondrial function was assessed by measuring calcium content, yield, oxygen consumption, and adenosine triphosphate-producing capacities. In addition, the mechanical function of the hearts was measured together with tissue adenosine triphosphate, creatine phosphate, and calcium content. In a separate series of experiments, the effect of temperature on the initial rate of respiration-supported calcium accumulation of mitochondria from freshly excised, nonperfused rabbit hearts was determined. The hearts made ischemic at 37 degrees C were severely depleted of tissue adenosine triphosphate and creatine phosphate. Their mitochondria accumulated calcium and the oxidative phosphorylating activity was impaired. During reperfusion, tissue and mitochondrial calcium levels were substantially increased, state 3 of mitochondrial respiration was further impaired, and the adenosine triphosphate-generating capacities were severely reduced. Diastolic pressure increased and there was no recovery of developed pressure. Isolated mitochondrial function of hearts made ischemic at 28 degrees and 22 degrees C was protected. There was a less marked increase in tissue and mitochondrial calcium, and the initial rate and total production of adenosine triphosphate were maintained. In these hearts there was an almost complete recovery of mechanical performance at reperfusion, whereas the ischemia-induced depletion of tissue adenosine triphosphate and creatine phosphate was not significantly reduced by hypothermia. The hearts made ischemic at 34 degrees C were only partially protected. These data suggest that a decrease in temperature from 37 degrees to 22 degrees C during ischemia did not significantly prevent depletion of adenosine triphosphate at the end of ischemia but reduced tissue and mitochondrial calcium overload, maintaining mitochondrial function. Thus in our experiments the protective effect of hypothermia might be related to a direct reduction of tissue and mitochondrial calcium accumulation rather than to a slowing in rates of energy utilization. This possibility is supported by the finding that in freshly excised, nonperfused rabbit hearts, hypothermia significantly reduced the initial rate of mitochondrial calcium transport. PMID- 2329832 TI - Three decades of treatment of esophageal squamous carcinoma at the Massachusetts General Hospital. AB - Seven hundred one patients with squamous cell carcinoma of the esophagus who were treated between 1950 and 1979 were retrospectively studied. The percentage of male patients decreased over the three decades (80% to 69%); the proportion of cigarette and alcohol abusers doubled. The esophageal carcinoma was located as follows: upper third, 24.7%; middle third, 52.8%, and lower third, 22.5%. There was disparity in clinical, surgical, and pathologic staging. More than two thirds of the patients thought to have stage II lesions preoperatively proved to have stage III lesions on pathologic examination; nearly one half of patients thought to have stage II disease intraoperatively were found to have pathologic stage III lesions. This "upgrading" of stage was chiefly a result of histologic recognition of nodal metastasis or extension of carcinoma into surrounding tissues. Operation was performed in 411 cases (58.6%) and resection was performed in 261 (37.2% overall). The postoperative death rate after resection fell from 30.5% in the 1950s to 10.4% in the 1970s, with respiratory complications the predominant cause of death. Analyses were based on treatment directed at the carcinoma itself: radiotherapy, 340 cases (48.5%); resection, 176 cases (25.1%); resection plus radiotherapy, 85 cases (12.1%); no definitive treatment, 100 cases (14.3%). Overall survival for the 701 patients was 13% at 2 years and 6% at 5 years (mean survival, 16.4 months); this did not differ by decade. Survival clearly differed by treatment (p = 0.001); resection plus radiotherapy provided the best survival (35% at 2 years; 20% at 5 years; mean of 32.5 months) followed by resection (18% at 2 years; 7% at 5 years; mean of 17.5 months), radiotherapy (9% at 2 years; 3% at 5 years; mean of 12.7 months), and no treatment (0% at 2 years; 0% at 5 years; mean of 2.5 months). Survival in patients who did not have resection did not differ by decade but survival in patients with resections improved in the last two decades. Patients with pathologic stage II lesions had greatly improved survival (54% at 2 years; 25% at 5 years; mean of 42.7 months) compared with patients with stage III disease (12% at 2 years; 6% at 5 years; (mean of 15.1 months) (p = 0.001). PMID- 2329833 TI - The continuing dilemma of general thoracic surgery. PMID- 2329834 TI - Pulmonary artery sling. PMID- 2329835 TI - Disappearing intracardiac masses. PMID- 2329836 TI - Any value for desmopressin acetate (DDAVP) in cardiopulmonary bypass operation? PMID- 2329837 TI - Bypass grafts for complex aortic coarctation: simplified approach. PMID- 2329838 TI - Brain amino acid concentrations in rats killed by decapitation and microwave irradiation. AB - The effect of death by decapitation or focused beam microwave irradiation (FBMI) on rat brain amino acid concentrations was investigated. Twenty-nine amino acids and related compounds were measured by ion-exchange chromatography in the cerebral cortex, hippocampus, striatum and substantia nigra of male Sprague Dawley rats killed by decapitation (n = 5) or by FBMI (n = 5). Alanine, GABA, ethanolamine and NH3 concentrations were significantly lower in all 4 brain regions of the FBMI group animals. Valine, leucine, tyrosine and phenylalanine levels were also lower in the hippocampus, striatum and substantia nigra of the FBMI group. The FBMI group showed less aspartate in the hippocampus and substantia nigra as well as less glycine in the cortex, hippocampus and striatum. In the FBMI group, the only amino acids exhibiting significantly higher levels were GSH in the striatum and substantia nigra and glutamate in the substantia nigra. These results show a significant impact of method of killing on the determination of baseline concentrations of brain amino acids. PMID- 2329839 TI - A new system for computer-assisted quantitative receptor autoradiography. AB - We have developed a computer-assisted analytic system for quantifying autoradiograms. The system was tested by studying the characteristics of high affinity serotonin binding sites (5-HT1) in rat brain sections, using [3H]5-HT as a radioligand. Autoradiographic data are digitized and transferred to a Macintosh II by means of a high speed, high resolution solid state camera. The physical characteristics of the device (uniformity, temporal stability, linearity) are such that the accuracy of the measurements obtained is highly satisfactory. The autoradiogram grey levels were measured and converted into radioligand concentrations (fmol/mg tissue) with the "BIOLAB" program which was specially written at our department in Macintosh Programming Workshop (MPW). The consistency of the measurements performed on small anatomical structures confirms the reliability of the system. The greatest discrepancies were due to the processing of the sections and also to the biological variability from one animal to another. The low cost of the device described, the high picture definition, the speed with which measurements can be obtained, the reliability of the system, and the original character of the program make it a valuable means to easier analyse quantitative autoradiography in pharmacological and physiological research. PMID- 2329840 TI - Ion-selective microelectrodes suitable for recording rapid changes in extracellular ion concentration. AB - A method for fabricating double-barrel, ion-selective microelectrodes with fine tips (0.5-1.5 microns) and rapid response times is described. When made into K(+) selective microelectrodes, the electrodes respond to changes in [K+]o with a time constant of 70-95 ms. The electrical response of these electrodes to common-mode voltages can be made to have a time constant of less than 2 ms, which minimizes electrical artifacts from field potentials. The application of these microelectrodes to the measurement of rapid, transient changes in retinal [K+]o is presented. PMID- 2329841 TI - Design of a microprocessor-controlled thermoregulated chamber for perfusing in vitro mammalian brain preparations. AB - A system is described that allows to perfuse in vitro isolated mammalian brain preparations obtained from adult guinea-pigs. It consists of a microprocessor controlled thermoregulation unit, a perfusion line and a perfusion/recording chamber. The main features of the thermoregulation unit include the ability to maintain stable temperatures between 10 and 37 degrees C and to precisely control the time course of the temperature changes. Using this system, perfused tissue blocks can be kept viable for 8-10 h. PMID- 2329842 TI - Measuring threshold of reinforcing brain stimulation by the method of constant stimuli. AB - A new method for measuring threshold of reinforcing electrical brain stimulation is described and results of a parametric study using this method are presented. Two groups of rats were trained under a concurrent FR-CRF (fixed ratio-continuous reinforcement) schedule of reinforcement provided by electrical stimulation of the lateral hypothalamus. The invariant intermittent FR schedule of reinforcement was used to maintain a baseline of behavior while a superimposed concurrent CRF schedule was used to measure reinforcement magnitude by varying the intensity of the CRF stimulus between zero and a maximum. Increasing and decreasing stimulus intensity on the CRF schedule leads to a gradual disappearance, respectively reappearance, of post-reinforcement pauses (PRPs) on the concurrent FR schedule, providing a criterion for changeover in schedule control, and thus, for threshold of reinforcement. To illustrate the measurement of threshold according to psychophysical requirements of the Method of Constant Stimuli, different CRF intensities were given in a randomized order. In one group of animals FR and CRF stimuli were given through the same electrode. Another group received FR and CRF stimuli through separate electrodes implanted in different hemispheres of the brain. For both groups the duration of the PRP was used as the dependent variable. The data of both groups showed a high negative correlation between the intensity of the CRF stimulus and the duration of the PRP, which is consistent with the results of experiments in which a Method of Limits procedure was used. On the basis of this relationship between CRF current intensity and PRP duration a threshold for reinforcing brain stimulation was calculated. PMID- 2329843 TI - [Prostaglandins: general properties and biosynthesis]. PMID- 2329844 TI - [The Stockholm syndrome]. PMID- 2329845 TI - [Sepsis caused by Candida parapsilosis. Joint and lung involvement in 2 patients with acute leukemia]. AB - Sepsis due to Candida parapsilosis with involvement of the joints and the lungs, respectively, is reported in two patients with acute leukemia. The first patient had ankle arthritis 72 days after an allogenic bone marrow transplant for acute lymphoblastic leukemia. The second patient had pneumonia with cavitation during pancytopenia after chemotherapy for acute monocytic leukemia. In both cases, C. parapsilosis sepsis responded to therapy with amphotericin B, associated with miconazole in the first patient and with 5-fluorocytosine in the second one. The rarity of septic foci during C. parapsilosis fungemia and the good outcome of both patients are emphasized. This good result was probably due to early antifungal therapy and the relatively rapid recovery of granulocytopenia. PMID- 2329846 TI - [The social system and accreditation of clinical trials]. PMID- 2329847 TI - [Tuberculous pseudochylothorax with thoracic wall involvement]. PMID- 2329848 TI - [Preliminary results of the analysis of donations carried out in Catalonia from 1985 to 1987]. PMID- 2329849 TI - [Castelman's disease and amyloidosis]. PMID- 2329850 TI - [Headache caused by gemfibrozil]. PMID- 2329851 TI - [Osteoporosis: the role of primary care in its prevention]. PMID- 2329852 TI - [Intracranial hemorrhage in patients undergoing anticoagulant treatment with acenocoumarol]. AB - Between 1980 and 1985, 2,012 patients treated with acenocoumarol were followed up. 31 of them had intracranial hemorrhage (ICH), representing an incidence of 1.54%. Its mortality rate was as high as 45%. The most common indication of anticoagulant therapy was cardiac valvular disease. No precipitating factors or concomitant hemorrhages in other sites were detected. Most patients with ICH were, at the time of the accident, within the therapeutic anticoagulant range. The most common localization of ICH was intraparenchymal; most of them developed after one year of anticoagulant therapy. In 32% of instances there was previous hypertension and previous stroke in 26%. ICH had a three times greater incidence in patients over 65 years. The patients who died showed larger hematomas than survivors in computed tomography. PMID- 2329853 TI - [Chronic kidney insufficiency and respiratory muscle function. Changes induced by treatment with 1,25(OH)2D3]. AB - A myopathy basically involving proximal respiratory muscles can develop in uremia. To evaluate respiratory muscle force in uremia, maximal inspiratory pressure (MIP) was measured in 27 patients with renal failure. MIP was very limited in patients with a creatinine clearance (Crc) lower than 10/ml/min 1.73 m2 not treated with hemodialysis (HD) and in patients on HD who were not treated with 1.25 (OH)2D3 (45 +/- 9 and 43 +/- 5 cm H2O, respectively), moderately reduced in patients on HD treated with 1.25 (OH)2D3 (58 +/- 5 cmH2O) and normal in patients with Crc higher than 10 ml/min 1.73 m2 (86 +/- 6 cmH2O). The treatment with 1.25 (OH)2D3 during 3 months promoted a significant increase in MIP and serum calcium level and a reduction in parathyroid hormone in patients with Crc lower than 10 ml/min. It was concluded that, in uremia, a respiratory muscle weakness partially reversible with vitamin D therapy may be found. PMID- 2329855 TI - [Hemorrhage in treatment with oral anticoagulants]. PMID- 2329854 TI - [Meningitis caused by Staphylococcus aureus. Analysis of 16 cases]. AB - During the period between 1982 and 1987, 16 cases of meningitis due to Staphylococcus aureus were diagnosed. Nine patients (56%) had undergone a previous neurosurgical operation and 5 of them were carriers of a cerebrospinal fluid (CSF) shunt. Seven patients (44%) had spontaneous meningitis. Fever and meningeal signs were the most common clinical findings. 50% of patients were comatose. The Gram stain of CSF showed Gram positive cocci in 7 cases. Blood cultures were positive in all patients with spontaneous meningitis and negative in the neurosurgical group. Overall mortality rate was 37.5%, and it was lower in the neurosurgical group than in the spontaneous meningitis. Other factors associated with a poor outcome were advanced age, bacteremia and septic shock. PMID- 2329856 TI - [Chronic lead poisoning caused by wine consumption: an epidemiologic study]. AB - An epidemiological study was carried out after the observation of a case of chronic lead poisoning so as to investigate its possible sources. An environmental evaluation was performed, including an analysis of the waters and wines consumed by the involved family; blood samples were obtained to assess lead levels in the consumers of the possibly implicated wines, with a comparative analysis of controls living in the same area. The study revealed that the source of the poisoning were the claret and white wines, which made soluble the lead when passing through the outlet tubes of the storage casks. The need for a greater surveillance of alimentary products by the corresponding authorities is emphasized. PMID- 2329857 TI - [Acute enteritis caused by Salmonella]. PMID- 2329858 TI - [Measuring the quality of life after liver transplant]. PMID- 2329859 TI - [High-dose intravenous immunoglobulins in thrombopenic purpura associated with human immunodeficiency virus infection]. PMID- 2329860 TI - [Lyme disease in the province of Sevilla]. PMID- 2329861 TI - [Endocarditis caused by Staphylococcus aureus as a complication of right heart catheterization]. PMID- 2329862 TI - [Burkitt's lymphoma and pregnancy]. PMID- 2329863 TI - [Unnecessarily premature and avoidable mortality]. PMID- 2329864 TI - [Saying yes to health economics. A case of a copied text that was previously published]. PMID- 2329865 TI - [Treatment of resistant or relapsing Hodgkin's disease with high doses of chemotherapy followed by autologous bone marrow transplant]. AB - Eleven patients with Hodgkin's disease were treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Four patients were resistant to initial therapy and 7 patients had relapsed but were progressing under second or third line therapy. The median time from initial diagnosis to transplantation was 44 months (range, 16 to 82). In 9 patients pre-ABMT consisted on high-dose CVB cyclophosphamide, etoposide and carmustine) chemotherapy, one patient was treated with BACT protocol (carmustine, cytosine arabinoside, cyclophosphamide and thioguanine) and other patient was treated with high-dose of busulfan and melphalan. In 8 patients complete remission (CR) was achieved, in one the remission was partial, one failed to respond and one case was not evaluable due to early death. Among CR patients, 2 died from late toxicity, and the other 6 remain in CR off therapy, one of them more than 33 months after ABMT. High-dose therapy produce severe myelosuppression in all patients. There were 3 treatment related death: one early death due to hemorrhagic myocarditis, one veno occlusive disease of the liver and one due to cytomegalovirus sepsis. The high complete response rate in these heavily pretreated patients suggests that there may be an indication for high-dose therapy and ABMT in earlier resistant Hodgkin's disease. Moreover under such conditions, treatment related morbidity would be expected to be lower. PMID- 2329866 TI - [Clinical application of radioimmunolocalization in colorectal cancer]. AB - We present preliminary results of radioimmunolocalization (RIL) of colorectal cancer with 131I labelled F(ab')2 fragments from monoclonal anti CEA and anti CA 19.9 antibodies in 22 patients with colorectal cancer and in one patient with metastases of unknown origin and high CEA value. Positive images were obtained in 7 of 11 primary tumors from 10 patients evaluated preoperatively; in 2 of 3 recurrences; in 9 of 12 metastatic localizations and in the unknown primary tumor localized, finally in the cecum. One local recurrence was not detected by any diagnostic methods, but RIL. There was not false-positive images. Therefore, RIL appears as a promising method for the diagnosis and follow-up of colorectal cancer. PMID- 2329867 TI - [Evaluation of an agglutination method of latex particles sensitized for the detection of vaginal candidiasis]. AB - We assayed clinically and experimentally a rapid method for detection of Candida in vagina by slide latex agglutination test (SLA). A total of 50 vaginal swabs from women with clinical evidence of candidiasis were examined for yeast by microscopical examination, mycological culture and compared with the Candida antigen test. We also studied experimentally the sensibility of the SLA test. We found better results with SLA than microscopy for rapid diagnosis. Of the women with certain vaginal candidiasis, 60% were diagnosed by microscopy and 100% by SLA. SLA provided similar information than culture, but is faster and the clinician can use its information choosing the appropriate antifungal treatment. PMID- 2329868 TI - [Vulvovaginal candidiasis]. PMID- 2329869 TI - [MALT lymphoma]. PMID- 2329870 TI - [Research in humans]. PMID- 2329871 TI - [When will saliva be used in hormonal protocols?]. PMID- 2329872 TI - [Diffuse myxedema as the presenting form of thyroid plasmocytoma]. PMID- 2329873 TI - [Sepsis in pregnancy probably caused by psittacosis of non-avian origin]. PMID- 2329874 TI - [Septic arthritis caused by a penicillinase-producing gonococcus]. PMID- 2329875 TI - [Serum ferritin in adult Still's disease]. PMID- 2329877 TI - [The delivery of care in cardiorespiratory arrest at a regional hospital]. PMID- 2329876 TI - [Lack of development of anti-Toxoplasma gondii IgG antibodies in an HIV-positive pregnant woman with positive anti-Toxoplasma IgM]. PMID- 2329878 TI - The role of experimental toxicology in safety evaluation: challenges facing the pharmaceutical industry. PMID- 2329879 TI - [Quality of the data in a patient registry]. PMID- 2329880 TI - [Do video screens cause skin damage?]. PMID- 2329881 TI - [Mercury-induced hypersensitivity rare after subcutaneous injection of vaccines]. PMID- 2329882 TI - [Physiologic origin of skin damage and systemic symptoms caused by visual display screens?]. PMID- 2329883 TI - [Half of all severe neurotrauma is related to alcohol]. PMID- 2329884 TI - [Azole derivatives, a new way of treating cryptococcosis]. PMID- 2329885 TI - [Bronchoscopy--applications and results in the assessment of lung cancer]. PMID- 2329886 TI - [Two years of HIV-testing activity. Two out of ten HIV positive individuals were discovered at venereology centers]. PMID- 2329887 TI - [Occurrence, characteristics and prognosis of medullary thyroid cancer in Sweden]. PMID- 2329888 TI - [Life quality assessment in clinical care research is a better instrument than traditional result measurements]. PMID- 2329889 TI - [Life quality assessment in obstructive lung disease. Poor correlation between spirometry and patients' evaluation]. PMID- 2329890 TI - [Quality of life--an important dimension in cardiovascular disease]. PMID- 2329891 TI - [Psychiatrists, HIV-infected patients and compulsion--keep medical therapy and social control apart!]. PMID- 2329892 TI - [Resorbable staple sutures for partial stomach and duodenal stump closure. Animal experiment studies]. AB - In two groups of pigs, 10 in each, partial gastrectomies with gastroduodenostomy (Billroth I) respectively gastrojejunostomy (Roux-en-Y) were performed. Absorbable lactomer (Polysorb, Auto-Suture) staple lines--a copolymer of glycolic acid/lactic acid-, used for the closure of the lesser curvature of the stomach and the duodenal stump, were safe. No suture dehiscence was observed. Macroscopic examination showed no major inflammatory adhesions around the staples. Microscopically inflammatory reactions around the staples in the gastrointestinal wall were found. Our results yielded no contraindication for clinical tests of absorbable sutures in gastrointestinal surgery. PMID- 2329893 TI - [The significance of the preoperative CEA value for the prognosis of rectal cancer]. AB - 254 patients were operated for rectal carcinoma in the period from 1980 to 1986. The number of curative procedures, recurrence rate and 5-year-survival rate were dependent on the preoperative CEA levels, which correlated with the tumour stage. Even within tumour stages with enough cases for statistical evaluation the CEA could be established as an independent prognostical variable. Within stage pT2N0M0 recurrence rate for patients with preoperative CEA level below 5 ng/ml was 29% compared to 64% in patients with higher serum levels. Median survival time for the two groups were 65 and 35 months, respectively. In stage of lymph node involvement median survival times of 46 and 25 months were observed for the groups with CEA levels above and below 5 ng/ml. The pattern of recurrence within the two stages seemed to be unaffected by the preoperative CEA level. Patients with preoperative elevated CEA represent a risk group with need of consistent postoperative follow-up and CEA controls. PMID- 2329894 TI - [Pancreatic circulation in experimental biliary pancreatitis]. AB - Measurements of pancreatic micro- and macrocirculation were performed to evaluate the pancreatitis-induced changes. Pigs were anesthetized and ventilated mechanically. Hypotension induced side-effects were avoided by adequate volume replacement. After laparatomy, splenectomy and gastroectomy the animals were enterotomized. Systemic hemodynamic parameters were monitored as well as pancreatic blood flow (Q), which was measured electromagnetically, and arterial and portal-venous blood gases. Pancreatic microcirculatory parameters were observed using fluorescence-videomicroscopy after i.v. administration of FITC dextran 150 and FITC labeled autologous erythrocytes. The pigs were randomly assigned to a control (n = 9) and a pancreatitis group (n = 10), the later being induced by the retrograde infusion of sodium-taurocholate. Systemic and pancreatic macrohemodynamic parameters remained constant in both groups, except for avdO2 and O2-consumption (O2-c) decreasing significantly in the pancreatitis group. At baseline 42% of all capillaries were perfused in both groups. In pancreatitis we detected focal areas with persistent stasis and areas which were continuously perfused. In these areas the portion of capillaries perfused by erythrocytes increased significantly to 67%. This was accompanied by an extravasation of FITC dextran. The finding of an unchanged Q beside reduced O2-c and avdO2 during pancreatitis is explained by the changes in pancreatic microcirculation. Focal stasis was observed beside areas showing typical signs of an acute inflammation: increased macromolecular permeability and capillary recruitment, e.g. oedema and hyperaemia. PMID- 2329895 TI - [Integrated concepts in the treatment of brachial plexus lesions]. PMID- 2329896 TI - [Organ preservation]. PMID- 2329897 TI - [Intraoperative autotransfusion in massive hemorrhage following thoracic abdominal trauma]. AB - In the University Hospital of Granada (Spain), 359 surgical trauma patients underwent intraoperative autotransfusion. The patients were divided into 2 groups, according to their blood loss: group I (blood loss less than or equal to 2000 ml) and group II (blood loss greater than 2000 ml). Patients from group I did not require homologous blood transfusion. So the high risk involved in this type of transfusion was avoided. Macroscopic haemoglobinuria was only found in those patients where the Solcotrans, Viavae type of autotransfusion system was used; with the Bentley ATS system, no macroscopic haemoglobinuria was registered. With patients from group II, however, that is, those with a blood loss of more than 2000 ml, we had to fall back on homologous transfusion in addition to retransfusing autologous blood. When the transfusion exceeds 4000 ml there is increasing bleeding, which requires treatment with fresh frozen plasma, platelets and/or fibrinogen. The mortality rate of patients in group II was very high but the patients died from the severity of their injuries or from postoperative complications which were not due to autotransfusion in itself with the exception of 3 patients who underwent massive autotransfusion (12,000 to 25,000 ml) and died from acute renal failure. The main indication for intraoperative autotransfusion is without doubt abdominal and thoracic trauma which lead to high blood loss. PMID- 2329898 TI - [Splenic cyst--a rare cause of epigastric expansion]. AB - Cysts are rare lesions of the spleen, and may be divided into parasitic and non parasitic types. After the parasitic cysts, the second most frequent group is the (secondary) posttraumatic form of non-parasitic cysts. The primary form (congenital and neoplastic) of the latter is the least frequent. Whereas splenectomy was the treatment of choice for lienal cysts until a few years ago, a change has occurred in the techniques of splenic salvage. Against the background of a case report of a primary epidermoid cyst the etiology, diagnostic measures, and the recent developments in conserving spleen surgery are discussed. PMID- 2329900 TI - Infectious adult croup. AB - From January 1980 to December 1987, seven patients with acute inflammatory swelling of the subglottic space were treated. Their ages ranged from 25 to 73 years. Medical history and symptomatology are similar to those characteristic of laryngotracheobronchitis (croup) in the pediatric age groups (i.e., an antecedent common cold followed by a barking cough and varying symptoms of upper airway obstruction). Physical findings before and after treatment were confirmed and documented by anteroposterior radiographs of the neck. Three patients required airway intervention but there were no deaths. To our knowledge there are no previous reports in the English literature describing this entity in adults. The purpose of this presentation was to introduce physicians, in general, and otolaryngologists, in particular, to this potentially serious infection. Our limited experience suggests that the pathogenesis and management of croup in adults are very similar to those in children. PMID- 2329899 TI - [Differential diagnosis of follicular neoplasm of the thyroid]. AB - Fifteen resected follicular adenomas and 15 well-differentiated follicular carcinomas of the thyroid gland were analysed to determine whether a differential diagnosis of both "follicular neoplasms" can be performed by cytological criteria exclusively. 150-200 tumor cell nuclei (TCN) were studied per case for their TCN profile area, perimeter, density and for stereological estimates including the new parameter Vv, volume-weighted mean particle volume. Flow-cytometric analyses included measurement of the DNA index, the percentage of cells in S-phase and in G2/M phase. Follicular adenomas and follicular carcinomas did not show any significant differences in stereological estimates related to TCN size. Both groups included similar proportions of diploid and aneuploid neoplasms. Aneuploid follicular neoplasms showed a significantly greater area, perimeter and volume of TCN as compared to diploid tumors, regardless of their histological diagnosis. From our results a differential diagnosis of follicular neoplasms cannot be performed on the basis of cytological aspirates exclusively. Infiltration of capsula or vessels remain the only safe indicators of malignancy in the absence of metastases. The lack of cytological differences provides evidence that some follicular adenomas are preinvasive carcinomas, not yet showing infiltrative growth at the time of resection. PMID- 2329901 TI - Optic nerve decompression via the lateral facial approach. AB - Two cases of visual loss after lateral orbital wall fracture are presented: one with retrobulbar hematoma and evidence of optic nerve compression who failed to respond to lateral canthotomy and high-dose corticosteroid administration, and the second with immediate, total blindness associated with fracture of the bony optic canal. In both, extradural decompression of the orbit and optic nerve was achieved through the lateral facial approach with partial return of visual acuity and without surgical complications. The role of orbital and optic nerve decompression in the management of patients with blindness following orbital trauma is controversial. Orbital decompression may be of value for cases of post traumatic visual loss unresponsive to medical management. If optic nerve injury is suspected as the cause, the additional step of decompression of the optic nerve is a logical but unproven procedure. The indications for optic nerve decompression are not established and should be considered only within the context of the specific needs of the individual patient. PMID- 2329902 TI - Malignant nasopharyngeal tumors in children. AB - From 1964 to 1984, 25 children with malignant tumors of the nasopharynx were seen, and their progress was followed at The Hospital for Sick Children in Toronto. Two types of malignancies: rhabdomyosarcoma and lymphoepithelioma were most prevalent with eight cases apiece. The presenting signs and symptoms were related to local and/or regional manifestations of disease. No child presented with signs or symptoms related to distant metastatic disease. The diagnosis and treatment of this series of patients are described briefly. The advent of combined treatment modalities in the past decade has improved the prognosis for nasopharyngeal tumors, especially for the rhabdomyosarcomas; in general, however, survival rates are still poor, approximating 50%. PMID- 2329903 TI - Delayed spontaneous return of hearing after acoustic tumor surgery: evidence for cochlear nerve conduction block. AB - Unlike the eventual resolution of facial paralysis in most patients with intact facial nerves, delayed hearing return after acoustic tumor resection is rare. This discrepancy in recovery has been ascribed to the inherent resilience of the facial nerve (a special visceral efferent nerve) to injury versus the cochlear nerve (a special somatic afferent nerve). In the presence of an intact cochlear nerve, hearing loss has been attributed to transection or spasm of the internal auditory artery or to direct mechanical trauma to the cochlear nerve during manipulation of the tumor. The possibility of a reversible conduction block in the cochlear nerve has not been considered. A review of three instances of delayed spontaneous hearing recovery several months after acoustic tumor resection suggests that a conduction block phenomenon can exist. This report describes the pathophysiology and the possible intraoperative predisposing features of this condition. PMID- 2329904 TI - Hearing after retrolabyrinthine vestibular neurectomy. AB - Thirty-four patients underwent vestibular neurectomies between September 1984 and January 1989. The first 15 patients operated on through January 1987 (and followed for a minimum of 2 years) were evaluated separately for long-term hearing preservation and freedom from vertigo spells. Audiograms taken at 1 postoperative month revealed no change in the pure tone averages of 25 patients and showed improved hearing of 20 to 30 dB in 5 patients. Two patients sustained losses of 18.5 dB and 21 dB, respectively. The speech discrimination scores remained the same in 17 patients, improved in 9, and were reduced in 6. Audiograms performed 12 to 40 months postoperatively showed preservation of the pure tone averages and speech discrimination scores when compared with the earlier 1-month postoperative audiograms in 73% of the patients. The speech discrimination scores, however, tended to fluctuate with the symptomatic course of each disease. Two patients developed major vertigo spells 1 1/2 years following surgery. Postoperative ice-caloric testing revealed no responses in 25 patients and markedly reduced responses in 6. There were no major complications or facial paralysis. The retrolabyrinthine vestibular neurectomy is an effective way to control vertigo with preservation of hearing and an acceptably low incidence of complications and side effects. PMID- 2329905 TI - Tonsillectomy and adenoidectomy: an inpatient or outpatient procedure? AB - Concern over the rising cost of health care has created a trend toward outpatient surgery. Because adenotonsillectomy is such a frequently performed procedure, there is pressure on many otolaryngologists to do this operation on an ambulatory basis. A prospective study was undertaken to evaluate the incidence and severity of postoperative hemorrhage, protracted emesis, and fever at specified times within the first 24 hours after surgery. Over a 1-year period, 1000 tonsillectomy and/or adenoidectomy patients were studied. There was a 2.1% incidence of serious complications within the first 6 postoperative hours. The incidence of serious hemorrhage, fever, and protracted emesis was 0.7% each. The incidence of significant complications between the 6th and 24th postoperative hours was 1.7%. Hemorrhage occurred in 0.4% of the patients, fever in 0.7%, and protracted emesis in 0.6%. The total incidence of hemorrhage during this time period was 1.1%. There were no deaths. The greatest percentage of complications occurred within the first 6 postoperative hours. Based on this study, outpatient tonsil and adenoid surgery should be followed by at least 6 hours of postoperative observation before discharge. The choice to perform ambulatory tonsil and adenoid surgery depends on the professional judgment of the operating physician based on this and other recent studies, the sophistication of the physician's ambulatory surgery center, and the medical and social background of the patient. PMID- 2329906 TI - Atypical findings in cephalic herpes zoster polyneuritis: case reports and radiographic findings. AB - The purpose of this presentation is to report six patients who were seen because of multiple cranial nerve deficits occurring within a clinical picture of herpes zoster of the head and trunk. The clinical behavior, diagnostic methods, treatment, and outcome of the patients in this series are reviewed. The vagus and cochleovestibular nerves were affected in all of the patients. Three patients had radiographic evidence of a mass in the nasopharyngeal region. Malignancies were ruled out by repeated biopsies. PMID- 2329907 TI - Tracheoesophageal speech: with and without tracheostoma valve. AB - The tracheostoma valve, developed by Blom and Singer combines the advantages of pulmonary air for phonation with hands-free speech. Patients have anecdotally reported "more normal speech" with the use of the valve. This study was designed to objectively determine if speech acoustic and temporal measures existed between tracheoesophageal puncture using the valve, and those without the valve prosthesis, during speech production among the same subjects. The speech samples of nine male laryngectomees were recorded with and without the valve. Six speech acoustic and temporal measures were calculated and compared under both speaking conditions. No statistically significant differences were found between the two speaking conditions for the six tasks measured. However, other advantages and disadvantages were observed and reported under the valve condition. PMID- 2329908 TI - Vocal cord paralysis resulting from neck injections in the intravenous drug use population. AB - Intravenous drug use patients present to the head and neck surgeon when injections are directed "in the pocket," or more appropriately, toward the internal jugular vein in the neck. The more common complications of this practice include the development of cellulitis, abscess, and venous thrombophlebitis and, potentially, pulmonary embolism and pseudoaneurysm of the carotid and subclavian arteries. Vocal cord paralysis as a result of neck injection in the intravenous drug-using population is rarely described, and a review of the literature has yielded only two reports addressing this uncommon phenomenon. During a 7 1/2-year period between October 1981 and June 1989, nine patients presented to Detroit Medical Center with hoarseness, upper-airway obstruction, or both following the injection of heroin or related substances into the neck. Otolaryngologic evaluation demonstrated unilateral or bilateral vocal cord paralysis coincident with recent neck injections. The clinical signs and symptoms, location of the injections, acute management, and subsequent complications are catalogued. Acute management of these patients consisted of airway assurance via tracheotomies when indicated and observation for the development of cellulitis, abscess, or more life-threatening neurovascular complications. Follow-up laryngeal examinations ranged from 4 months to 4 1/2 years and found no demonstrable return of vocal cord function in any of the nine patients. PMID- 2329909 TI - Surgical therapy of obstructive sleep apnea in children with severe mental insufficiency. AB - Obstructive sleep apnea is the underlying cause of a variety of pediatric maladies, including pulmonary hypertension and failure to thrive. In children, unlike adults, obstruction secondary to lymphoid hyperplasia is often encountered; adenotonsillectomy restores airway patency. Patients who fail this procedure, such as children with cerebral palsy and associated muscular hypotonia, may face tracheotomies. We report on 10 pediatric patients with severe mental insufficiency and obstructive sleep apnea in whom palatal hypotonicity and lack of adenotonsillar hypertrophy was identified. Uvulopalatopharyngoplasty was performed in conjunction with adenotonsillectomy to enlarge the diameter of the nasopharyngeal inlet with successful resolution of the obstructive symptoms in eight patients. The remaining two children required more surgery. This procedure is presented as a possible alternative to tracheotomy in selected patients. PMID- 2329910 TI - Is outpatient suction cautery tonsillectomy safe in a community hospital setting? AB - Tonsillectomy and adenotonsillectomy are frequently performed operations. They are typically done as a day-of-surgery admission with discharge on the first postoperative day. Five hundred consecutive tonsillectomies and adenotonsillectomies performed by the authors were retrospectively reviewed to determine if these procedures could safely be performed on an outpatient basis. Primary postoperative hemorrhage was found to be rare using the suction cautery technique. Secondary hemorrhage occurred most commonly on the sixth postoperative day and the overall postoperative bleed rate was 7%. Our conclusion was that suction cautery tonsillectomy and adenotonsillectomy were safe to perform on an outpatient basis. PMID- 2329911 TI - Inner ear autoantibodies in patients with rapidly progressive sensorineural hearing loss. AB - Recognition of immune-mediated sensorineural deafness that responds to immunosuppressive therapy has led to a search for a diagnostic assay to identify inner ear autoantibodies. Without a confirmed diagnosis of autoimmune disease, many patients have undergone inappropriate immunosuppressive treatment or developed irreversible inner ear damage. Serum from patients with progressive sensorineural hearing loss (n = 54), ulcerative colitis (N = 5), normal controls (N = 14), and animals with experimental autoimmune sensorineural hearing loss (EASNHL) were analyzed by Western blot against fresh bovine inner ear antigen preparations. The hearing loss group (19 [35%]) showed a single-or double-band migrating at 68,000 molecular weight (MW), differing from the normal group (1 of 14 [7%]) which showed a similar band (P = .031). Upon analysis by two-dimensional gel electrophoresis both the EASNHL guinea pigs and a patient reacted against identical components of inner ear antigen. These results suggest an autoimmune basis for disease in patients reacting against the 68,000 MW antigen. PMID- 2329912 TI - Tracheobronchial aspiration of foreign bodies in children: a study of 94 cases. AB - Over the last seven years, there has been an increase in the number of children admitted to our hospital because of aspirated foreign bodies. An inhaled foreign body can become a serious matter if it results in acute respiratory distress or if it remains unrecognized for a long period in the bronchial system. Then, as a result of inflammatory tissue reactions, it can be extracted only with great difficulty. Of our 94 children with foreign body aspiration, 24% had been treated initially on the basis of a different diagnosis. In 30% of all cases, the children were admitted more than 3 days after aspiration. One third of the patients already had signs of marked inflammation on admission. Early treatment, under general anaesthesia, proved to be safe even for small babies. Bronchoscopic examinations should not last more than approximately 1 hour. All children who had complications after bronchoscopy (6%) recovered fully after treatment, except for one child who died of respiratory failure. A diminution of complications in children with inflammatory signs on admission was observed when they were treated before the operation with antibiotics and methylprednisolone. PMID- 2329913 TI - Spectral analysis of airflow sounds in patent versus occluded tracheostomy tubes: a pilot study in tracheostomized adult patients. AB - Cannula occlusion is a life-threatening postoperative complication of tracheostomy. Current management largely relies on nursing care for prevention of fatalities because no proven mechanical, machine-based support monitoring exists. The objective of this paper was to address the problem of monitoring the state of cannula patency, based on analysis of airflow acoustic spectral patterns in tracheostomized adult patients in the patent and partially occluded cannula. Tracheal airflow sounds were picked up via a condenser microphone air-coupled to the skin just below the tracheal stoma. Signal output from Mic was amplified, high-pass filtered, digital tape-recorded, and analyzed on a mainframe computer. Although airflow frequencies for patient cannulae were predominantly low-pitched (0.1 to 0.3 kHz), occluded tubes had discrete high-pitched spectral peaks (1.3 to 1.6 kHz). These results suggest that frequency analysis of airflow sounds can identify a change in the status of cannula patency. PMID- 2329914 TI - Interstitial laser phototherapy assisted by magnetic resonance imaging: a new technique for monitoring laser-tissue interaction. AB - The rapid technological advances of magnetic resonance imaging, laser fiberoptics, and compatible probes may allow treatment of deep and sometimes surgically unreachable tumors of the head and neck with minimal morbidity through interstitial laser phototherapy. In this study, a new application of magnetic resonance imaging was developed to monitor and quantify laser-induced tissue damages. Pig skin was exposed to increased levels of argon laser (514.5 nm) at energy densities between 62.5 and 375 J/cm2 as determined by an accurate and reproducible method of dosimetry. Thermal profiles were recorded using an infrared sensor and T1- and T2-weighted magnetic resonance images were taken; afterward, biopsies were performed to quantitate the level of tissue damage. Our results demonstrate that above a certain threshold of laser energy, the magnetic resonance imaging findings are temperature dependent. Appropriate development of a scale matching laser energies, temperature profiles, T1- and T2-weighted magnetic resonance images, and histological quantitation of tissue destruction will allow us to optimize the three-dimensional control and monitoring of laser tissue interactions. PMID- 2329915 TI - Use of a linear stapler for postlaryngectomy pharyngeal repair: a preliminary report. PMID- 2329916 TI - Device for testing the Singer-Blom prosthesis. PMID- 2329917 TI - Prolactin messenger ribonucleic acid levels, prolactin synthesis, and radioimmunoassayable prolactin during the estrous cycle in the golden Syrian hamster. AB - The purpose of this study was to observe the molecular dynamics of pituitary prolactin (PRL) gene expression during the estrous cycle of the Golden Syrian hamster. PRL messenger ribonucleic acid (mRNA) levels, PRL synthesis (3H-PRL in the incubation media or incubated pituitary after a 3 hr incubation with 3H leucine), and radioimmunoassayable (RIA) PRL (in the incubation media or incubated pituitary after the 3 hr incubation) were measured in the morning (0930 1100 hr) on each day of the cycle. We observed that all of these PRL indices declined or did not change from Day 2 to Day 3 of the cycle. From Day 3 to Day 4 (proestrus), however, PRL mRNA levels increased 33-38% and media 3H-PRL increased 32-42%, while there were no significant changes in pituitary 3H-PRL, or RIA-PRL in the media or pituitary. From Day 4 to Day 1 (estrus) there was a reciprocal change in the levels of 3H-PRL in the pituitary vs. the media, with the former increasing 37-50% and the latter decreasing 25-32%. Pituitary RIA-PRL also increased 45-64% from Day 4 to Day 1 while media RIA-PRL did not change. These data are consistent with the following hypothesis: On the morning of proestrus (Day 4) in the hamster, PRL mRNA levels are elevated compared to those on Day 3, signaling an increase in PRL synthesis. This newly synthesized PRL is shunted into a "readily releasable" pool on the morning of Day 4 (contributing to the afternoon surge of serum PRL), and into a "preferentially stored" pool by the morning of Day 1 (for release in response to cervical stimulation and use as a luteotrophin to maintain early pregnancy should fertilization occur). PMID- 2329918 TI - Tibenelast, 5,6-diethoxybenzo(B)thiophene-2-carboxylic acid, sodium salt (LY186655), is an orally active anti-asthma compound in the guinea pig. AB - Anaphylactic shock was induced in actively sensitized guinea pigs by free inhalation of a high dose of ovalbumin (10 mg/ml) aerosol. Tibenelast (LY186655), 5,6-diethoxybenzo(b)-thiophene-2-carboxylic acid, sodium salt, proved to be a potent orally active compound against anaphylactic shock induced by high dose antigen aerosol. When a lower aerosol challenge (0.05 mg/ml) was employed, bronchoconstriction was observed with a concomitant increase in lung resistance (RL) and a fall in dynamic compliance (Cdyn). Tibenelast at 25 mg/kg p.o. prevented these changes. Tibenelast was 10 times more potent than aminophylline by i.v. administration; normalization of pulmonary function was achieved at 1 mg/kg i.v. Tibenelast was synergistic with epinephrine. Combination of no-effect doses of epinephrine (0.025 mg/kg s.c.) and tibenelast (0.1 mg/kg i.v.) normalized pulmonary function. The oral dose response curve of tibenelast was enhanced with the co-administration of epinephrine. These data suggest that tibenelast may act at a site different from that of epinephrine, although the mechanism of action of tibenelast is unclear at present. Tibenelast may be of significant value in the treatment of asthma and other respiratory diseases. PMID- 2329919 TI - Purification of L-[3H]nicotine eliminates low affinity binding. AB - Some studies of L-[3H]nicotine binding to rodent and human brain tissue have detected two binding sites as evidenced by nonlinear Scatchard plots. Evidence presented here indicates that the low affinity binding site is not stereospecific, is not inhibited by low concentrations of cholinergic agonists and is probably due to breakdown products of nicotine since purification of the L [3H]nicotine eliminates the low affinity site. PMID- 2329920 TI - Blockade of the pre- and postjunctional effects of angiotensin in vivo with a non peptide angiotensin receptor antagonist. AB - Recent reports indicate that some imidazole-5-acetic acid derivatives are competitive antagonists of angiotensin II receptors. However, to our knowledge, there is no published information regarding: 1) what constant infusion rate of these non-peptide angiotensin receptor blockers is necessary to effectively antagonize angiotensin receptors in vivo, 2) whether imidazole-5-acetic acid derivatives antagonize both prejunctional and postjunctional angiotensin receptors, and 3) whether effective levels of these compounds exert non-specific actions and/or partial agonist activity. To address these issues, either vehicle, 2-butyl-4-chloro-1-(2-nitrobenzyl) imidazole-5-acetic acid (CV-2961; 30 and 100 micrograms/min) or a standard angiotensin receptor blocker, 1Sar8Ile-angiotensin II (100 ng/min), was infused intravenously into captopril-treated rats that were prepared for in situ perfusion of their mesenteric vascular beds. Infusion of CV 2961 for two and one-half hours did not alter arterial blood pressure, mesenteric perfusion pressure, plasma aldosterone level, or mesenteric vascular responses to sympathetic nerve stimulation or exogenous norepinephrine. The higher dose of CV 2961 (100 micrograms/min) completely blocked angiotensin II-induced enhancement of vascular responses to sympathetic nerve stimulation and shifted the angiotensin dose-response curve 10-fold to the right with respect to angiotensin II-induced increases in mesenteric perfusion pressure. The effects of the lower dose of CV-2961 (30 micrograms/min) on these actions of angiotensin II were not statistically significant. 1Sar8Ile-angiotensin II abolished both the prejunctional and postjunctional effects of angiotensin II. We conclude that in intact rats CV-2961, infused at 100 micrograms/min, antagonizes both prejunctional and postjunctional angiotensin II receptors, yet has a somewhat greater effect on the prejunctional actions of angiotensin II. CV-2961 is devoid of partial agonist activity, and no non-specific actions of CV-2961 are evident. Imidazole-5-acetic acid derivatives may find considerable utility as pharmacological probes and as therapeutic agents. PMID- 2329921 TI - Mixed agonist/antagonist properties of NAN-190 at 5-HT1A receptors: behavioural and in vivo brain microdialysis studies. AB - 1-(2-Methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine, NAN-190, is a novel compound with putative 5-HT1A antagonist properties. In the present study, the effects of NAN-190 were examined with regard to functional pre- and post-synaptic 5-HT1A receptor-mediated events, using in vivo brain microdialysis and behavioural techniques. Our findings provide evidence that NAN-190 acts as a mixed agonist/antagonist at central 5-HT1A receptors. Thus, NAN-190 blocked (+)8 OH-DPAT-induced behaviour in reserpinized rats, indicating antagonist properties at postsynaptic 5-HT1A receptors. However, the compound was also able to decrease the release of 5-HT in vivo, tentatively due to an agonist action at somatodendritic 5-HT1A autoreceptors. These data extend previous information on the pharmacological profile of NAN-190 and further emphasizes the difference between pre- and postsynaptic 5-HT1A receptors in brain. PMID- 2329922 TI - Lability of red blood cell membranes to lipid peroxidation: application to humans fed polyunsaturated lipids. AB - Red blood cell membranes (RBCM) were used to estimate human red blood cell lability to lipid peroxidation in vitro. RBCM were prepared from blood collected from humans fed diets with either 3 or 15% polyunsaturated fatty acids for 80 days. RBCM were isolated by centrifugation, and oxidative stress was induced by in vitro incubation with 0.1 or 0.5 mM tert-butyl hydroperoxide (t-BOOH) in the presence of 0.5 mg added hemoglobin. Lipid Peroxidation was evaluated by measurement of thiobarbituric acid-reactive substances (TBARS). Lipid peroxidation correlated with the protein content of RBCM in both noninduced and t BOOH-induced lipid peroxidation systems. TBARS production was dependent on the amount of t-BOOH added to the RBCM. The production of TBARS by RBCM incubated with 0.5 mM t-BOOH was correlated with arachidonic acid content in the red blood cells (RBC) from which RBCM were prepared. The methodology developed was useful for comparative estimations of the lability of RBCM to lipid peroxidation. PMID- 2329923 TI - Synergism between penicillin G and the antimicrobial ether lipid, rac-1 dodecylglycerol, acting below its critical micelle concentration. AB - rac-1-Dodecylglycerol (DDG) and penicillin G (Pen G) act synergistically to dramatically lower the minimum inhibitory concentration (MIC) of each other in four Gram-positive bacteria studied. At one-half its MIC, DDG ether lowered the MIC of Pen G 10- to 80-fold. Under the same conditions, Pen G lowered the MIC of DDG 4- to 7.5-fold. The critical micelle concentration of DDG was determined to be 7.93 mg/ml (0.0305 mM), which is approximately two-fold greater than the minimum inhibitory concentration of DDG determined in the presence of a protein free chemically defined medium. This finding suggests that DDG is not killing bacteria through its detergent action. Pen G also did not alter the critical micelle concentration of DDG, which indicates that the synergism between these two agents is not related to micelle formation. PMID- 2329924 TI - Fatty acid hydroxylase system in the Japanese harvest mouse, Micromys minutus. AB - Liver microsomes of the Japanese harvest mouse (Micromys minutus), which is the smallest known mammal among rodents, catalyze the hydroxylation of various fatty acids (C8 to C18) to the corresponding omega-hydroxy and (omega-1)-hydroxy derivatives. Although laurate is most effectively hydroxylated among saturated fatty acids by liver microsomes of other species, harvest mouse liver microsomes most effectively catalyze the hydroxylation of decanoate. From inhibitor and cofactor studies, and from the substrate specificity for hydroxylation, it was concluded that omega- and (omega-1)-hydroxylation of fatty acids are catalyzed by different cytochrome P-450 species in the liver microsomes of the harvest mouse. PMID- 2329925 TI - Isolation of a guanine-malondialdehyde adduct from rat and human urine. AB - A 1:1 adduct of guanine with malondialdehyde (MDA) was isolated from rat and human urine. This compound was shown to be identical to a synthetic adduct prepared according to the procedure of Seto et al. (Bull. Chem. Soc. Jpn. 58, 3431-3435, 1985). The UV, NMR and other characteristics of the compound were consistent with the tricyclic pyrimidinopurine structure proposed by these investigators. Its endogenous origin is indicated by its presence in the urine of rats fed an MDA-free diet, and by the observation that its excretion increased following iron or carbon tetrachloride administration. It may serve as a marker for nucleic acid modification caused by lipid peroxidation in vivo. PMID- 2329926 TI - Biochemical and functional abnormalities in hypercholesterolemic rabbit platelets. AB - This study was designed to elucidate changes in rabbit platelet lipids induced by a cholesterol rich diet and to explore the possible correlation of these lipid changes with platelet abnormalities. Pronounced biochemical alterations were observed when serum cholesterol levels of 700-1000 mg% were reached. Hypercholesterolemic (HC) platelets contained 37% more neutral lipids and 16% less phospholipids than the controls. Lysolecithin, cholesterol esters and phosphatidylinositol (PI) levels were increased in HC platelets, and the levels of phosphatidylcholine (PC) were decreased. The cholesterol/phospholipid molar ratio of lipidemic platelets increased from 0.55 +/- 0.011 to 0.89 +/- 0.016 (P less than 0.01) in eight weeks. HC platelets had 90% more arachidonic acid (AA) in the PI than normal platelets. No significant changes in AA of PC were observed. Platelet function was monitored by the uptake and release of [14C]serotonin in platelet rich plasma (PRP), using varying concentrations of collagen as an aggregating agent. The uptake of [14C]serotonin in HC and normal platelets ranged from 78-94%. The percent of [14C]serotonin released from normal and HC platelets was proportional to the concentration of collagen. However, lipidemic platelets were hyperreactive to low concentrations of collagen. Incorporation of 50 microM acetylsalicylic acid into the aggregating medium suppressed the release of [14C]serotonin in normal PRP by more than 90%, but had only a partial effect on lipidemic PRP. PMID- 2329928 TI - [Physical training for the middle-aged and elderly]. PMID- 2329929 TI - [The training of nurses in the USA (a general description of the training variants for American nurses)]. PMID- 2329927 TI - Uptake and metabolism of dolichol and cholesterol in perfused rat liver. AB - The uptake of dolichol and cholesterol by perfused rat liver was studied. When these radioactive lipids were incorporated into egg phosphatidylcholine liposomes, both dolichol and cholesterol appeared initially in the supernatant and in the microsomal fraction and, later on, in the mitochondrial-lysosomal fraction. The lipids taken up were esterified to some extent, but no phosphorylation of dolichol occurred. Incorporation of dolichol and cholesterol into lipoproteins increased the efficiency of uptake, which was receptor-mediated in this case. Accumulation of these lipids occurred in lysosomes followed by a transport to the endoplasmic reticulum (ER). Both labeled dolichol and cholesterol appeared in the bile. In the case of dolichol, the majority of this radioactivity was not associated with the original substance itself, and probably represented lipid-soluble catabolites. In the case of cholesterol, most of the radioactivity was associated with bile acids. It appears that, in contrast to the receptor-mediated uptake of lipoproteins from the perfusate, the uptake of liposomal lipids involves a different mechanism. After association with the plasma membrane, the lipids enter into the cytoplasm and are transported to the ER and later to the lysosomes. PMID- 2329930 TI - [A cuff for compressing the vein in intravenous injections]. PMID- 2329931 TI - [The quality management of nurses' work in a general hospital]. PMID- 2329932 TI - [Disseminated sclerosis]. PMID- 2329933 TI - [Heart rhythm disorders in children]. PMID- 2329934 TI - [AIDS in oral medicine]. PMID- 2329935 TI - [The care of sick children in the nephrology department]. PMID- 2329936 TI - [The prevention of infectious diseases]. PMID- 2329937 TI - [The potentials for using pressor reflexotherapy in fatigue]. PMID- 2329938 TI - [Recipe file cards for dietetic dishes]. PMID- 2329939 TI - [The use of the diving reflex in treating supraventricular paroxysmal tachycardia]. PMID- 2329940 TI - [The clinical picture and treatment of pulmonary edema]. PMID- 2329941 TI - [Medical first aid in bone fractures and dislocations]. PMID- 2329942 TI - [Gastric and duodenal intubation]. PMID- 2329943 TI - [The organization of child nutrition in preschool institutions]. PMID- 2329944 TI - Antibacterial activity of the essential oil of Thymus serpylloides subspecies gadorensis. AB - The in vitro antibacterial activity of the essential oil obtained from the flowering apex of Thymus serpylloides ssp. gadorensis against various micro organisms is reported. Moreover, the main chemical groups found in this essential oil are described. PMID- 2329945 TI - Cohesion between oral streptococci and Neisseria pharyngis on saliva-coated glass, in the presence and absence of sucrose. AB - Ten strains of oral streptococci, comprising nine species, were screened for their in vitro cohesive interactions with a freshly isolated strain of Neisseria pharyngis. Strains of mutans streptococci, Streptococcus salivarius, Streptococcus sanguis I, Streptococcus milleri and Streptococcus mitis were able to cohere with N. pharyngis cells attached to a salivary pellicle adsorbed to glass. The cohesion was either due to coaggregation between the different genera or modification of the salivary pellicle by N. pharyngis MW2. S. sanguis II and Streptococcus oralis strains could not cohere with the N. pharyngis strain. Extracellular polysaccharide formed from sucrose was found to mediate cohesion between certain strains of mutans streptococci or S. oralis and N. pharyngis MW2. PMID- 2329946 TI - Immunization against Haemophilus influenzae. PMID- 2329947 TI - Skin cancer in Geraldton, Western Australia: a survey of incidence and prevalence. AB - A survey of the incidence and prevalence of non-melanocytic skin cancer in Geraldton, Western Australia, was undertaken in November 1987. All residents aged 40 to 64 years whose names were on the electoral roll on August 1, 1987 were invited to undergo a whole-body skin examination by a dermatologist. When a skin cancer was suspected, participants were referred for treatment to their usual medical practitioner. Subjects were asked to recall incident skin cancers over the preceding two years, and medical records were searched for confirmatory evidence. Histological confirmation of all lesions, both prevalent and incident, was sought and sections were obtained for a standardized review. The prevalence of confirmed non-melanocytic skin cancer in those aged 40 to 64 years was 7.0% in men and 4.7% in women. The prevalence of basal-cell carcinoma (BCC) was 6.5% in men and 4.5% in women while the prevalence of squamous-cell carcinoma (SCC) was 1.2% in men and 0.3% in women. The estimated incidence rate of non-melanocytic skin cancer in this age group was 1560 per 100,000 person-years. The estimated incidence rate of BCC in men was 1335 per 100,000 person-years, and in women 817 per 100,000, while in men the estimated incidence rate of SCC was 890 per 100,000 person-years, and in women it was 289 per 100,000 person-years. PMID- 2329948 TI - Medical problems in joint replacement patients: a retrospective study of 243 total hip arthroplasties. AB - Two hundred and forty-three total hip arthroplasties were performed in 217 patients over a five-year period in one institution. Seventy-one per cent had one or more significant preoperative medical problems, 22% being referred for preoperative management to a specialist physician. Thirty per cent of patients experienced re-activity of medical problems after operation; in 41% of patients a physician review was sought while in a further 40% the problems were apparently unnoticed or not acted upon. There was a positive correlation between preoperative and postoperative medical problems (P less than 0.001). Fifteen per cent of patients developed complications and one patient died. There was a highly significant trend towards longer hospital stay in patients with medical problems and complications (P less than 0.001). It is concluded that there is a high incidence of medical problems in joint replacement patients, that these problems have an influence on the morbidity and cost of the procedure, and that management of these problems can be improved. PMID- 2329949 TI - Bone marrow transplantation for childhood acute lymphoblastic leukaemia after marrow relapse. AB - Children with acute lymphoblastic leukaemia in whom relapse in bone marrow occurs have a poor outlook when treated with chemotherapy alone. Twenty-seven patients with childhood acute lymphoblastic leukaemia were treated for marrow relapse with high-dose chemotherapy with or without total body irradiation followed by bone marrow transplantation (BMT). Twenty patients received allogeneic marrow from partially or completely matched histocompatible donors. In this group, nine patients (45%) were free of disease with a median follow-up of 57 months (range, 22 to 126 months) after transplantation, four (20%) died from interstitial pneumonitis and seven (35%) died after a further relapse. Seven patients received autologous marrow collected while they were in remission. In this group, one patient died from infection and six died after a further relapse. We conclude that allogeneic BMT is more effective than autologous transplantation and results in long-term disease-free survival in a significant number of patients. New methods are needed to eradicate residual disease in the patient and to purge marrow ex vivo. PMID- 2329950 TI - Neurocysticercosis: an under-recognized cause of neurological problems. AB - Neurocysticercosis is an uncommon, and under-recognized condition in Australia. Changes in immigration patterns may lead to a rising prevalence in this country. Epilepsy is the most common presentation, but it has many other variable forms of neurological manifestations. Eight cases are described, all in immigrants from Eastern Europe, Asia or Central America; the disease was presumably acquired before arrival in Australia. Six patients had symptoms for two to 30 years before the diagnosis was made and, in some cases, the first neurological manifestations appeared decades after initial infection. In patients with active disease a successful outcome followed therapy with praziquantel and corticosteroids. We advise that all patients requiring treatment be admitted to hospital for corticosteroid and anticonvulsant therapy to minimize the clinical deterioration which may result from therapeutic destruction of larvae. PMID- 2329951 TI - Stern-Tanner disease: a radical cure. PMID- 2329952 TI - Thrombocytopenia after snake envenomation. PMID- 2329954 TI - The International Society of Doctors for Environment. PMID- 2329953 TI - The injecting and sexual behaviour of intravenous drug users in Sydney. PMID- 2329955 TI - Isolated penetrating injury of the gall bladder. PMID- 2329957 TI - Sensory examination. PMID- 2329956 TI - In-vitro sensitivities to fluoroquinolones of urinary tract pathogens from patients from a spinal unit. PMID- 2329958 TI - Seat-belt injuries of the spine in children and young adolescents--an increasing cause for concern. PMID- 2329959 TI - Werewolves down under--where are they now? PMID- 2329960 TI - [Locker room pharmacology]. PMID- 2329961 TI - Prevalence of liver disease and infection by hepatitis B, delta virus, and human immunodeficiency virus in two Spanish penitentiaries. AB - We studied the prevalence of liver disease and the carrier state for hepatitis B (HBV), delta virus (HDV) and HIV-1 infection in two Valencian penitentiaries, one for males and the other for females. Serological results were correlated with history of intravenous drug addiction, alcohol abuse, homosexuality or prostitution (high-risk groups), and duration and number of internments. A high prevalence of increased transaminase levels (52.2%) and serological markers for HBV infection (66.5%) was observed amongst the inmates, figures being higher amongst high-risk individuals and inmates confined for more than 6 months. No signs of HDV or HIV-1 infection were found amongst the prison staff. Anti-HIV-1 positivity was observed most frequently amongst individuals combining both drug abuse and homosexuality/and prostitution. PMID- 2329962 TI - Phase II trial of etoposide and cis-diaminodichloro-platinum in patients with refractory and relapsed Hodgkin's disease: Cancer and Leukemia Group B (CALGB) Study 8353. AB - A phase II study was conducted by the Cancer and Leukemia Group B (CALGB) in patients with refractory and relapsed Hodgkin's disease (HD) to assess the activity of the combination of etoposide and cis-platin. Twenty-seven patients were entered; 22 were evaluated for this report. Treatment consisted of etoposide (VP-16), 80 mg/m2 IV over 1 hour and cis-platin, 20 mg/m2 IV over 1/2-1 hour; both agents were given daily for 5 days and repeated every 21 days. All patients had received at least 2 prior chemotherapy regimens, had measurable disease, and most (86%) had a performance status of 0-1. In the 22 evaluable patients, there were 4 complete responses (18%) and 4 partial responses, for an overall response rate of 36% (95% Cl: 17.2%, 59.3%). Response duration was from 2.1 to 31 months. Significant toxicity was observed with this regimen. Ten patients (45%) had leukopenia less than 1,000/microliters, and 11 patients (50%) had thrombocytopenia less than 25,000/microliters. Serum creatinine levels reached greater than 2.0 in 14% of patients. Seven patients (32%) had severe nausea and vomiting. VP-16, cis-platin appears to be an active combination in HD; however, their combined activity is only marginally better than reported single-agent activity for VP-16 in the doses and schedule used. Further studies of related combinations in HD are currently under evaluation by the CALGB. PMID- 2329963 TI - Bone marrow relapse occurring as first relapse in children with acute lymphoblastic leukemia. AB - In a retrospective review which covered the whole Dutch childhood population of approximately 3 million children we studied the prognosis in 164 children with acute lymphoblastic leukemia (ALL) who were initially treated between 1973 and 1983, and who had an isolated bone marrow relapse occurring as first relapse. Until their first relapse, the patients were initially treated according to standard protocols, while treatment for relapse was heterogeneous, and not intensive. Second complete remission (CR) was attained by 78% of the patients. The median duration of second CR was 9 months, the median survival 13 months. Multivariate analysis showed that the duration of the first CR was the most significant variable with regard to prognosis. None of the patients who developed their bone marrow relapse during initial treatment, i.e., within 24 months from diagnosis, survived. Among the 73 patients who relapsed after cessation of the initial treatment there were 19 long-term disease-free survivors, 14 of whom had not developed subsequent relapses after 48(+)-125 + months. From this study we conclude that treatment in children with first bone marrow relapse has to be intensified. PMID- 2329964 TI - 2' Deoxycoformycin (pentostatin) for refractory non-Hodgkin's lymphoma: a CALGB phase II study. AB - Seventy-six eligible patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with 2'-deoxycoformycin (pentostatin) at a dose of 4 mg/m2 intravenously weekly for three weeks and then every other week for a minimum of five total treatments. All patients had measurable disease, near normal hematologic, renal, and hepatic function, and a performance status of 0 or 1. Severe hematologic toxicity was observed in 13% of patients; severe renal or neurologic toxicity was observed in less than 5% of patients. There were no treatment-related deaths. Objective therapeutic responses were seen in 16% of patients (five complete response [CR] and seven partial response [PR]). However, in three of the patients achieving CR and one patient achieving PR, dexamethasone was employed as an anti-emetic, making the response of these patients to pentostatin difficult to evaluate. There were eight responses (3 CR) in patients with diffuse histologies and four responses (2 CR) in patients with nodular or mixed histologies. Three responses were in patients with a T-cell phenotype. Three of five patients with diffuse well-differentiated lymphoma (IWF A) responded. We conclude that 2' deoxycoformycin is only minimally active at this dose and schedule against refractory or relapsed NHL. The possibility that low grade B- and T-cell malignancies are more sensitive to 2' deoxycoformycin deserves further investigation. PMID- 2329965 TI - Erythrocyte fatty acid profiles in childhood malignancy. AB - The erythrocyte fatty acid composition was determined for 79 children using gas chromatography. The stearic:oleic acid ratio (SOR) was significantly lower in those children with newly diagnosed malignancies than in a reference group of healthy children. However, a control group of children with chronic, non malignant conditions were also found to have a low SOR. These results suggest that the erythrocyte SOR cannot be used as a tumour marker in children. PMID- 2329966 TI - Nosocomial septicemia in the cancer patient: the influence of central venous access devices, neutropenia, and type of malignancy. AB - Nosocomial septicemias that occurred over a 32-month period on an inpatient medical oncology service were reviewed. One hundred four episodes of septicemia occurred in 84 patients, 33% with solid tumors and 67% with leukemia or lymphoma. Sixty were primary septicemias, with the remainder being secondary. Of the 118 isolates recovered, 42% were Gram-positive organisms, 45% Gram-negative organisms, and 13% were fungi. Coagulase-negative staphylococci and Escherichia coli were the most common Gram-positive and Gram-negative isolates, respectively. The effect of the type of malignancy, neutropenic status, and presence of a central venous access device (CVAD) on the isolate(s) recovered was studied. Coagulase-negative staphylococci were more commonly isolated from leukemia lymphoma patients (26% vs. 3%, P less than .01), while Gram-negative isolates (63% vs. 36%, P = .01), specifically Klebsiella species (21% vs. 5%, P = .02), were more common in solid tumor patients. Staphylococcus aureus was isolated more frequently from non-neutropenic patients than from those with neutropenia (19% vs. 4%, P = .02). Gram-positive isolates were more commonly found in patients with a CVAD (51% vs. 29%, P = .03), in particular coagulase-negative staphylococci (29% vs. 2%, P less than .001). In contrast, Gram-negative isolates (62% vs. 34%, especially Klebsiella species (22% vs. 3%, P less than .01) and S. aureus (18% vs. 5%, P = .07) were more commonly isolated from patients with no CVAD. Neither neutropenia nor the presence of a CVAD predisposed to early mortality. Our data suggest that empiric antimicrobial coverage for presumed nosocomial septicemia in the febrile cancer patient should include vancomycin for patients with a CVAD to cover coagulase-negative staphylococci and a cephalosporin for patients with solid tumors, especially those without a CVAD, to cover Klebsiella species. PMID- 2329967 TI - Comparative study on the pharmacokinetics of 7-hydroxy-methotrexate after administration of methotrexate in the dose range of 0.5-33.6 g/m2 to children with acute lymphoblastic leukemia. AB - Concentrations of 7-hydroxy-methotrexate (7-OH-MTX) were determined in serum samples obtained after 266 infusions of methotrexate administered to 58 children with acute lymphoblastic leukemia. The dose of methotrexate (MTX) was in the range of 0.5-33.6 g/m2. Pharmacokinetic parameters (metabolic index, drug/metabolite ratio, half-life) of 7-OH-MTX and their relationship to the kinetics of methotrexate were analyzed. A great variability was observed in the extent and time-course of the metabolite formation. The concentration of the metabolite was higher than that of the parent compound at any examined time after the end of the 24 hours' infusion. The increase of 7-OH-MTX levels at the end of the methotrexate infusion was found to be proportionate to the increase of the dose of MTX. Males had significantly higher metabolite levels than did females (P less than 0.01) in the dose range of 0.5-8.0 g/m2. The age of the patients also significantly influenced the rate of the metabolite formation. The serial number of the treatment courses did not have effect on the metabolism of MTX. Dose dependency of the elimination half-life of the metabolite was found. Although a tendency was observed that patients in continuous complete remission had higher metabolite levels than those who relapsed, the difference was not significant. Further studies are needed to determine the clinical importance of 7-OH-MT. PMID- 2329968 TI - "Reversible encephalopathy and seizure. . ." by Hurwitz et al., 1988. PMID- 2329969 TI - Multifocal neuroblastoma. PMID- 2329970 TI - Fatal varicella infection in a child associated with thymoma and immunodeficiency (Good's syndrome). AB - An 8-year-old male underwent excision of an encapsulated thymoma. Four months later he presented with disseminated, fatal varicella. Evaluation of his immune status during the terminal illness revealed hypogammaglobulinemia and lymphopenia consistent with a diagnosis of Good's syndrome (immunodeficiency with thymoma). This is the first case of Good's syndrome reported in a child and the first case of fatal varicella associated with Good's syndrome. The combination of this rare pediatric tumor and immunodeficiency is discussed. Despite specific antiviral therapy, varicella remains a deadly disease in the immunocompromised host. PMID- 2329971 TI - Pulmonary fibrosis associated with low-dose adjuvant methyl-CCNU. AB - Pulmonary fibrosis is a serious side effect of nitrosourea therapy, occurring most frequently in patients treated with BCNU. Pulmonary fibrosis developed in a 63 year-old male patient while being treated with adjuvant methyl-CCNU for rectal carcinoma. This toxicity is rare with methyl-CCNU, having only been reported once previously. The case of methyl-CCNU-induced pulmonary fibrosis reported here occurred at a much lower total dose than the first reported case (604 mg/m2 vs. 2,733 mg/m2). Details of the case history, including radiographic and pathologic findings, are presented. PMID- 2329972 TI - Severe acute encephalopathy following inadvertent intrathecal doxorubicin administration. AB - In a female with acute lymphoblastic leukemia, inadvertent doxorubicin administration intrathecally caused severe, life-threatening, acute encephalopathy with high-pressure hydrocephalus. Ventriculo-peritoneal shunting led to complete reversal of hydrocephalus with progressive disappearance of the acute encephalopathy. PMID- 2329973 TI - [Mucogingival problems in pedodontics]. PMID- 2329974 TI - [Clinico-epidemiological research on the incidence of masticatory dysfunctions in periodontal patients]. AB - The frequency of symptoms and signs of the craniomandibular-system dysfunctions were analysed in 70 patients selected because of their periodontal disease. The data obtained were compared with other data connected with epidemiological studies made on not-selected people. PMID- 2329975 TI - [Sialographic and computed tomographic studies in pathology of the major salivary glands]. AB - A retrospective study is reported which took place over 3 years (1986-1989) and included 99 patients (57 men and 33 women, age range 8-90 years) with lesions attributable to salivary gland diseases. Patients were examined using CAT and sialographic tests. From an analysis of the results it is clear that sialography retains its importance as a means of diagnosis in inflammatory diseases, calculosis and autoimmune disorders, whereas CAT should be used as the preferential diagnostic test for neoplastic lesions. PMID- 2329976 TI - [The therapy of carcinomas in the oromaxillofacial area. IV. Carcinomas of the buccal mucosa]. AB - The authors describe the therapeutic modalities for the care of epidermoid carcinoma of the buccal mucosa. Surgery and radiotherapy are equally effective in the early lesions, while for the advanced disease the therapy should always be combined. PMID- 2329977 TI - [Postextraction hemorrhage: treatment with an infrared photocoagulative technic]. AB - The use of the infrared ray photocoagulative technique is reported in 80 patients with moderate and/or intensive postextraction haemorrhage. The results obtained confirm the effectiveness of the technique in dentistry in which it has thus for not been used, with the purpose of making choice of suitable haemostatic technique wider in case of need. PMID- 2329979 TI - [Odontogenic botryoid cyst]. AB - The clinical and histopathological features of two cases of botryoid odontogenic cyst are reported. The lesion is an uncommon variant of the lateral periodontal cyst and differs from this with regard to the histopathological features and the biological behaviour. PMID- 2329978 TI - [An infrared photocoagulative technic in the prevention of hemorrhagic complications in oral medicine]. AB - The infrared ray clotting technique has been successfully employed in numerous branches of medicine and surgery. Here its usefulness is demonstrated in dentistry, particularly in the treatment of haemorrhagic complications in oral and extractive surgery in patients suffering from clotting disturbances. The physical features of infrared radiation make it possible to perform a targeted, instantaneous tissue necrosis of depth proportional to exposure time. Its speed, simplicity and effectiveness make infrared ray clotting the haemostatic intervention of choice in every single event. PMID- 2329980 TI - [Aggressive juvenile fibromatosis]. AB - Aggressive juvenile fibromatosis is not metastasizing disease characterized by a neoplastic proliferation of fibroblasts that rarely involves surrounding bone. The Authors describe one case observed by them and suggest the surgical procedure as elective treatment of the disease. In cases where a mandibular resection is performed, a simultaneous bone reconstruction, when feasible, is indicated. PMID- 2329981 TI - [Beta-thalassemia and its orodental implications. II. A clinical study]. AB - The paper reports the findings of a study of 46 subjects affected by beta thalassemia major who underwent periodic transfusion therapy. A reduced incidence of the caries process was observed, above all in subjects treated from the first months of life. After a short review of the main problems posed by these patients during dental treatment, the Authors propose a course of preventive antibiotic treatment to be carried out before the start of dental work. PMID- 2329982 TI - The problem-solving curriculum evaluation and development model. AB - Evaluation has been a feature of nurse education programmes for many years, yet many nurse educators are still struggling with inappropriate, time-consuming procedures, that yield little reward. This paper describes an evaluation and development model that is in the process of implementation at The Royal Free Hospital and Friern School of Nursing. The model has generated much interest from other schools of nursing, and has so far proved easy to use, flexible in application to any course, and has turned evaluation into a purposeful, fruitful, enjoyable and rewarding process. PMID- 2329983 TI - Self awareness: conceptual influences, contribution to nursing, and approaches to attainment. AB - The paper examines the concept and dimensions of 'self', and the notion of self awareness. It discusses the questions raised by the issues involved, and the central relationship of the concept of self-awareness to nursing, and some specific therapeutic models. It suggests that awareness of 'self', including the incorporation of the models described, makes a predominantly positive contribution to both general and psychiatric nursing. The use of some current teaching approaches is discussed, and congruence and balance are urged for nurse teachers involved in facilitating the development of the skills involved. (Solely for ease of reading all persons are referred to throughout by a single gender, however, in order to redress the conventional imbalance, the feminine pronoun is chosen). PMID- 2329984 TI - Purposes, values and objectives in adult education--the post-basic perspective. AB - In the light of increasing calls for nurse education to adopt an education model based on the principles of adult learning this paper examines the place of objectives in adult education and how they relate to the general purposes and values in education. The development of the use of objectives is discussed from its origins in the behaviourist school of thought through to the more recent approach adopted by those purporting to embrace the principles of adult education. Implications for the use of objectives in nurse education, and in particular post-basic nurse education, are then considered. PMID- 2329985 TI - Towards a strategy for teaching information skills to student nurses. AB - It is being increasingly recognised that nursing needs to be constructively and critically informed by a body of scientific knowledge, and that practitioners need to develop active and independent learning styles which enable them to access, use and evaluate such knowledge. This approach has led to many teachers reexamining their approaches to teaching and learning, with an increasing emphasis upon cultivating lifelong learning and in providing students with the skills to facilitate this process. It is against this backdrop that the authors developed a comprehensive information skills package for student nurses undertaking an ENB Diploma in Nursing Science/Registered General Nurse Course (ENB Pilot Scheme Course). The package was designed specifically for use within the Newcastle Polytechnic Library though with modifications, it could be used in other venues. This paper explores the rationale and structure of the package and its subsequent implementation and evaluation. PMID- 2329986 TI - The development of teachers and the problem of criteria of effectiveness: an analysis of two approaches. AB - Two learning packages designed for the development of teachers are discussed particularly in terms of their implicit criteria of effectiveness. The potential utility of the packages in nursing education is considered. It is argued that 'Curriculum in Action' has the advantage of providing nurse teachers with the skills to take control of their practice, whilst 'Preparing for Change' seeks to alter practice from above. PMID- 2329987 TI - External examiner system in traditional nurse education--issues to be resolved. AB - Nurse education is in the process of adopting the practices of higher education establishment. One such practice is the external examiner system. Unfortunately this system is not without its shortcomings. A number of potential areas of difficulty in using this system are looked at in this paper. These range from problems associated with the selection of the external examiner to the balance of power between the external examiner and the course team. It is pointed out that nurses may, in their desire for validation and increased status, leave aside their growing critical abilities and accept without reservation and to their detriment the traditional practices of the higher education system. PMID- 2329988 TI - The importance of marketing in nurse education. AB - There can be little doubt that changes in the National Health Service (NHS) heralded by the 1989 Government White Paper, Working for Patients, have significant implications for nurse education. Not least will be the need for Colleges and Schools of Nursing to present a high profile in terms of the services they offer. This paper explores the concept of marketing and its increasing importance to nurse education. It examines Giles' three propositions in relation to marketing, and suggests that these may be applied successfully to organisations providing a service, as well as those producing material goods. It looks at how and why marketing is necessary to nurse education, and suggests that marketing is an essential tool in assisting the School to achieve its objectives. Marketing strategies are discussed in detail, looking first at methods of research, then at the processes used to sell the courses being offered. These include the techniques of developing the offering, marketing the offering, facilitation, valuation and finally, promotional communication. The paper concludes by summarising the reasons why marketing techniques will be essential to the future success of nurse education, at a time when it is so vital to ensure that a well qualified nursing workforce is prepared to meet the challenges of the future. PMID- 2329989 TI - The socialisation of nurses in clinical settings: a dual focus critique of a research study. AB - This is a two-pronged critique of a study of the socialisation of neophyte nurses in a neonatal intensive care unit in the USA. The authors, respectively an educationalist and a nurse researcher experienced in neonatal intensive care, agreed in finding that the study fell short of what it promised, but differed as to their reasons. They decided to publish their critiques as a complementary pair, in the hope that those supervising research students would benefit from seeing a disappointing study simultaneously in two perspectives, educational and clinical. PMID- 2329990 TI - Health visitor education and training: what is the future? PMID- 2329991 TI - Developing a system of student nurse profiling through action research. AB - This article concerns the early stages of a research study which attempted to improve the assessment of student nurses' clinical competence by means of profiling. During the course of the paper the reasons for undertaking assessment will be considered, the existing assessment approach will be briefly reviewed, the use of action research as the method of inquiry will be addressed, and the initial findings from the study described. PMID- 2329992 TI - The nursing student and the psychiatric patient with AIDS: a case study. AB - AIDS is one of the most pressing challenges facing health care professionals today. Nurse educators are determining the role of the student in this new clinical situation. This case study provides a look at some of the core issues that may be encountered when a nursing student cares for a patient with this deadly disease. A critical incidence format is used to outline the experience and to present the implications for nursing education. PMID- 2329993 TI - Curriculum innovation and the management of change. AB - Change in Nurse Education is occurring at such a rate that interest in the management of change is increasing. This article constructs an anatomy of an innovation and considers elements which helped and hindered the change process. The innovation was the development of a new RMN curriculum which was a cooperative venture between three health districts. Continuous assessment, student centered learning and a humanistic approach were all embodied in the innovation. By interviewing the Change agents the innovations are considered in a way which highlights internal and external resistances to change. The use of planning, personal effort and a collegial approach are noted as assisting factors when used within a humanistic framework and a normative re-educative change strategy. Ownership of the innovations is seen as a measure of the strategies success. PMID- 2329994 TI - Muscarinic cholinergic receptor mediated inhibitory transduction of adenylate cyclase activity in subcellular fractions from rat heart: improved detection in sodium phosphate buffer. AB - Cholinergic inhibition of myocardial adenylate cyclase activity in cell-free fractions has been known for many years, although the reported degrees of inhibition have been rather modest (20-30%), notably in rat heart fractions. The present study conducted with rat heart subcellular fractions document following major findings: (1) Myocardial adenylate cyclase activity and notably its cholinergic inhibition in cell-free fractions are notoriously labile to storage at 4 degrees C whereas its stimulation by beta adrenergic receptor agonists or forskolin are reasonably well preserved during storage. (2) Among four buffers (Tris, glycylglycine, imidazole and sodium phosphate) examined, sodium phosphate buffer afforded the best preservation of cholinergic inhibitory response of adenylate cyclase. (3) The commonly used biochemical buffers, notably imidazole, exerted deleterious effect on the cholinergic inhibition of myocardial adenylate cyclase such that it was considerably attenuated or barely detectable; this explains, in part, the reported poor inhibition of myocardial enzyme by others. (4) Imidazole buffer, on the other hand, augmented beta adrenergic and forskolin stimulated adenylate cyclase activity. The likely significance of these findings is discussed from consideration that the observed differential influence of buffers results from differential actions on the interactions between the components (receptor/coupling G proteins/catalyst) comprising autonomic receptor coupled adenylate cyclase system in rat heart. PMID- 2329995 TI - Effects of platelet-activating factor on single potassium channel currents in guinea pig ventricular myocytes. AB - Platelet-activating factor (PAF) has been implicated as one of the mediators of cardiac anaphylaxis. This phospholipid has been shown to have numerous effects on a variety of tissues, including the heart. Among these effects are alterations in the resting potential and generation of arrhythmias at very low concentrations. This suggests that PAF may modulate the activity of the background, inwardly rectifying potassium current (IK1). Thus, the effects of PAF on IK1 were examined at the single channel level. Ventricular cells were isolated from adult guinea pig hearts and single channel currents recorded from cell-attached patches. PAF had substantial effects on the single channel currents at sub-nanomolar concentrations (10(-11) to 10(-10) M). PAF initially caused flickering of the channels, followed by a gradual prolonged depression of channel activity. Since these potassium channels play a major role in determining the resting potential and excitability of the cardiac cell, the effects of PAF on IK1 may play a major role in the deleterious electrophysiological actions of PAF on the heart. PMID- 2329996 TI - The catabolism of endogenous adenine nucleotides in rat liver mitochondria. AB - The degradation of intramitochondrial adenine nucleotides to nucleosides and bases was investigated by incubating isolated rat liver mitochondria at 37 degrees C under non-phosphorylating conditions in the presence of oligomycin and carboxyatractyloside. Within 30 min the adenine nucleotides were degraded by about 25 per cent. The main products formed were adenosine and inosine the contents of which increased five- to sevenfold. Compartmentation studies revealed that about 50 to 60 per cent of the adenosine formed remained inside the organelles whereas inosine was almost completely released into the surrounding medium. Outside the mitochondria only very small amounts of adenine nucleotides were detected. Similar incubations in the presence of [14C]-adenosine yielded no [14C]-inosine ruling out extramitochondrial adenosine deamination. It is concluded that endogenous adenine nucleotides can be degraded in mitochondria via AMP dephosphorylation and subsequent adenosine deamination. A purine nucleoside transport system mediating at least the efflux of inosine from the mitochondria is suggested. PMID- 2329997 TI - Role of fatty acids of (n-3) and (n-6) series on alpha-linolenic acid desaturation and chain elongation in HTC cells. AB - The desaturation and chain elongation of [1-14C] alpha-linolenic acid were studied in HTC cells preincubated for 24 h in the presence of different unlabeled fatty acids of (n-3) and (n-6) series. After 24 h in the presence of [1-14C] alpha-18:3, cells transformed this acid into labeled 20:5 and 22:5(n-3) through the desaturation-elongation pathway and into 20:3 and 22:3(n-3) by the elongation reactions. The preincubation of HTC cells with (n-3) fatty acids (alpha-18:3, 20:5 and 22:6) produced an increase in the amount of [1-14C] alpha-18:3 that remained in the cells without being metabolized and consequently, a decrease in the last product formed, the 22:5(n-3) was observed. Simultaneously, the desaturation-elongation products decreased significantly and those of the elongation pathway were not modified, except when the cells were pre-incubated with the last fatty acid of this family (22:6) which increased this metabolic route. Fatty acids of (n-6) series (gamma-18:3, 20:3, 20:4 and 22:4) decreased the desaturation-elongation pathway and increased the elongation route from [1 14C] alpha-18:3. From these results, it can be concluded that fatty acids of (n 3) family and intermediates of (n-6) series would impair the [1-14C] alpha-18:3 metabolism at the delta 6 desaturation step. The fatty acid composition of the cells was also modified by the preincubation with (n-3) and (n-6) acids showing a decrease on delta 9 desaturation activity. PMID- 2329998 TI - Interleukin-1 alpha and phorbol ester inhibit collagen synthesis in osteoblastic MC3T3-E1 cells by a transcriptional mechanism. AB - The effects of recombinant human interleukin-1 alpha (IL-1) on procollagen gene expression were examined in the clonal mouse osteoblastic cell line MC3T3-E1. Cells were grown in Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum and 50 micrograms/ml ascorbic acid. Collagen synthesis was assessed as [3H]proline incorporation into collagenase-digestible protein (CDP). Procollagen mRNA levels were determined by Northern blot analysis using a 32P-labeled alpha 1(I) cDNA. Transcription rates were determined by nuclear run-off assay. IL-1 at 1-1000 pg/ml caused a concentration-dependent inhibition of CDP, which was maximally reduced by 75-80%, and a parallel reduction of procollagen alpha 1(I) mRNA levels. The effects of IL-1 were mimicked by the tumor promoter phorbol 12 myristate 13-acetate (PMA) at 1-100 nM, which inhibited CDP and reduced procollagen alpha 1(I) mRNA levels to a similar extent. The effects of IL-1 and PMA were independent of prostaglandin production, since indomethacin did not alter the inhibitory effect of either agent on CDP. Neither IL-1 (up to 10 ng/ml) nor PMA (100 nM) affected adenylate cyclase activity, while forskolin (10 microM), PTH (10 nM) and prostaglandin E2 (1 microM) stimulated adenylate cyclase activity 3- to 5-fold. However, forskolin (10 microM) and (Bu)2cAMP (100 microM) failed to alter CDP or procollagen alpha 1(I) mRNA levels. IL-1 (1 ng/ml) and PMA (100 nM) reduced transcription of the alpha 1(I) procollagen gene by 70% and 80%, respectively, while alpha 2(I) transcription was decreased by 59% and 53%. Neither IL-1 nor PMA affected transcription of the beta-actin or beta-tubulin genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2329999 TI - Messenger RNA stabilization accounts for elevated basic fibroblast growth factor transcript levels in a human astrocytoma cell line. AB - Basic fibroblast growth factor (bFGF) is a potent autocrine and paracrine mitogen for cells of mesodermal origin. Although the protein is present in substantial amounts in a variety of tissues, the level of mRNA is undetectable in most normal tissues. This has led to speculation that bFGF mRNA is very unstable, but the half-life of this mRNA has not been described. A number of mRNAs encoding growth factors and growth-related proteins are known to be short-lived and posttranscriptionally regulated. In the present study we have examined the half life of bFGF mRNA in two human tumor cell lines, which contain high (U87-MG) and low (T98-G) steady state bFGF mRNA levels. The half-life of bFGF mRNA, determined after transcriptional arrest with actinomycin-D, was approximately 10 min in T98 G cells, but was extended to 120 min in the presence of cycloheximide. In contrast, bFGF transcripts in U87-MG cells were very stable with a half-life considerably greater than 5 h. This was not attributable to a general stabilization of mRNA in the U87-MG line, since the half-life of c-myc mRNA in the two cell lines was similar (10 and 15 min in T98-G and U87-MG, respectively). Cycloheximide had no effect on the steady state level of bFGF in U87-MG cells. These findings suggest that posttranscriptional processes play an important role in the regulation of bFGF transcript levels and demonstrate that loss of posttranscriptional regulation could contribute to elevated bFGF expression in some tumors. PMID- 2330000 TI - Expression of endogenous and transfected apolipoprotein II and vitellogenin II genes in an estrogen responsive chicken liver cell line. AB - A recently described chicken liver cell line, LMH, was characterized to evaluate responsiveness to estrogen. Expression of the endogenous apolipoprotein (apo) II gene was induced by 17 beta-estradiol when LMH cells were cultured with chicken serum. The response was low and yielded apoll mRNA at only 0.3% of the level seen in estrogenized rooster liver. Higher levels of apoll mRNA were achieved when LMH cells were transiently transfected with an expression plasmid for estrogen receptor. A transfected apoll gene was strongly expressed only when cotransfected with receptor. Expression of the endogenous vitellogenin (VTG) II gene was not detected. However, when cotransfected with a receptor expression plasmid, VTG II reporter plasmids were expressed in LMH cells in response to 17 beta-estradiol. These results suggest that estrogen responsiveness of LMH cells is limited by the availability of functional receptor. Low levels of estrogen receptor mRNA were detected in LMH cells, and receptor binding sites and mRNA were greatly increased following transient transfection with a receptor expression plasmid. Using this transient transfection protocol, several VTG II reporter plasmids were compared in LMH cells and chick embryo fibroblasts. A plasmid containing VTG II estrogen response elements linked to a heterologous promoter was regulated by estrogen in both cell types. In contrast, reporter plasmids containing the VTG II promoter were regulated by estrogen in LMH cells but were not expressed at all in chick embryo fibroblasts. These results suggest that regulation of the VTG II gene involves cell type-specific elements in addition to estrogen response elements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330001 TI - Overexpression of full-length human glucocorticoid receptor in Spodoptera frugiperda cells using the baculovirus expression vector system. AB - We have expressed a full-length human glucocorticoid receptor (hGR) in Spodoptera frugiperda (Sf9) cells using the baculovirus expression vector system (BEVS). The level of expression is approximately 100-fold greater than in CEM-C7 cells. Between 0.5-1.0 mg hGR can be generated per liter of Sf9 cell culture. The expressed hGR is capable of binding glucocorticoids with specificity and high affinity. Covalent labeling with 3H-dexamethasone mesylate and Western blot analysis using a polyclonal antibody indicate that the molecular weight of the expressed protein is approximately 94 k. The nonactivated receptor sediments as a 8-9S complex in sucrose gradients and can be heat activated to a 4S form. The activated receptor is capable of retarding the migration of a 23 base-pair DNA fragment containing the glucocorticoid response element from the tyrosine aminotransferase gene. These data indicate that the expressed GR displays characteristics identical to those of GR from mammalian cells. By scaling up this culture we can, for the first time, obtain enough purified full-length receptor for crystallographic and functional studies which could provide new insight into exactly how hGR works. PMID- 2330002 TI - Evolution of insulin-like growth factor I (IGF-I): structure and expression of an IGF-I precursor from Xenopus laevis. AB - By means of a cloning strategy employing the polymerase chain reaction, we have isolated and characterized cDNAs for Xenopus laevis insulin-like growth factor I (IGF-I). These cDNAs encode a primary IGF-I translation product of 153 residues that demonstrates considerable amino acid sequence similarity with IGF-IA peptides from other species. Fifty-seven of 70 residues of the mature protein are identical among human, rat, chicken, and Xenopus IGF-I, while less amino acid conservation is found at the COOH-terminus (25/35 identities) or at the NH2 terminus (24/48 identities) of the precursor protein. Despite the lower degree of structural similarity at the NH2-terminus, in vitro studies of IGF-I biosynthesis and proteolytic processing support a conserved function for the atypically long 48 residue NH2-terminal signal sequence in directing the nascent IGF-I peptide through the secretory pathway. The 5'-untranslated region of Xenopus IGF-I mRNA matches the human, rat, and chicken sequences in greater than 90% of 279 nucleotides. IGF-I mRNAs from all four species encode a conserved upstream open reading frame of 14 amino acids starting 240-250 nucleotides 5' to the translation start site, suggesting a possible role for this region in modulating IGF-I gene expression. The X. laevis IGF-I gene is transcribed and processed into three mRNAs of 1.6, 2.1, and 3.0 kilobases in liver, and IGF-I mRNAs can be detected in liver, lung, heart, kidney, and peritoneal fat of adult animals. These studies demonstrate that both the IGF-I protein precursor and potential regulatory regions of IGF-I mRNA have been conserved during vertebrate evolution, and indicate that like several other polypeptide growth factors, IGF-I may be of fundamental importance in regulating specific aspects of growth and development in all vertebrates. PMID- 2330003 TI - The rat insulin receptor: primary structure and conservation of tissue-specific alternative messenger RNA splicing. AB - To investigate whether alterations in the polypeptide structure of the insulin receptor might explain the heterogeneity observed in its properties between species and in different tissues, we obtained the complete primary structure of the rat liver insulin receptor precursor by cDNA cloning and sequencing. The rat proreceptor contains 1357 amino acids and has 95.2% identity with deduced polypeptide sequences reported for the human insulin receptor precursor. In addition, the rat liver insulin receptor cDNA was similar to the form of the human insulin receptor mRNA that contains Exon 11 in its coding region, which undergoes tissue-specific alternative splicing. Using the polymerase chain reaction to amplify a cDNA segment corresponding to this region in several rat tissues, the splicing pattern of sequences homologous to Exon 11 was found to be highly conserved, providing further evidence that these two forms of the insulin receptor may serve important functional or regulatory roles. These studies have also identified subtle variations in the primary structure of the insulin receptor which may influence its properties between species. PMID- 2330004 TI - Unique molecular properties of a urea- and salt-stable DNA-binding estrogen receptor dimer covalently labeled with the antiestrogen [3H]desmethylnafoxidine aziridine. A comparison with the estrogen-receptor complex. AB - A new antiestrogen affinity ligand for the covalent labeling of estrogen receptors, [3H]desmethylnafoxidine aziridine, has been used to investigate the salt- and temperature-independent formation of DNA-binding estrogen receptor forms from untransformed (300 kilodaltons) receptor. Calf uterine estrogen receptor proteins labeled with [3H]estradiol or [3H]desmethylnafoxidine aziridine were quantitatively transformed (greater than 90%) to their DNA-binding configuration in low ionic strength buffers by brief exposure to 3 M urea at 0 C. The urea effect was hormone-dependent and partially reversible. The transformed receptors were purified (ca 250-fold) by affinity chromatography on single stranded DNA-agarose in the continued presence of 3 M urea to prevent transformation reversal. Scatchard analyses revealed a single class of high affinity radioligand binding sites (Kd = 0.34 nM) unchanged by urea-induced transformation and purification. The DNA-binding receptor form labeled with [3H]desmethylnafoxidine aziridine was stable as a probable dimer in 3 M urea with 0.4 M KCl and displayed no evidence of size (Stokes radius 7.3 to 7.5 nm; 4.2 to 4.3 S; Mr = 136,800) heterogeneity. Sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis indicated the presence of an intact 67 kDa steroid binding receptor subunit. Reverse-phase chromatography of the covalently labeled receptor on C4 and phenyl stationary phases revealed no evidence of structural heterogeneity. The surface charge of the estrogen- and antiestrogen-receptor complexes, however, was distinctly different in both the presence and absence of 3 M urea. Thus, exposure to urea was an effective salt- and temperature independent means for achieving the complete transformation of receptor to its stable DNA-binding dimer configuration. The ligand-induced differences in receptor surface charge and the urea effects on DNA-binding (but not hormone binding) suggest that both electrostatic and hydrophobic or hydrogen bonding receptor domains are influenced by ligand binding. PMID- 2330005 TI - Structure of two in tandem human 17 beta-hydroxysteroid dehydrogenase genes. AB - Two human 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) genes (h17 beta-HSDI and h17 beta-HSDII) included in tandem within an approximately 13 kilobase pair fragment were isolated from a genomic lambda EMBL3 DNA library using cDNA encoding human 17 beta-HSD (hpE2DH216) as probe. We have determined the complete exon and intron sequences of the two genes as well as their 5' and 3'-flanking regions. Human 17 beta-HSDII contains six exons and five short introns for a total length of 3250 base pairs. The exon sequence of h17 beta-HSDII is identical to the previously reported hpE2DH216 cDNA while the overlapping nucleotide sequences of the corresponding exons and introns of h17 beta-HSDI and h17 beta HSDII show 89% homology. In addition, we have used the hpE2DH216 cDNA to demonstrate the widespread expression of 17 beta-HSD mRNAs in steroidogenic and peripheral target tissues. These new findings provide the basis for a better understanding of the molecular mechanisms involved in 17 beta-HSD deficiency and peripheral sex steroid metabolism. PMID- 2330006 TI - Uterine estrogen receptor interaction with estrogen-responsive DNA sequences in vitro: effects of ligand binding on receptor-DNA complexes. AB - Interaction between the mouse estrogen receptor (ER) and its responsive element (ERE) were examined in vitro using tissue extracts and an oligonucleotide containing a Vitellogenin A2 ERE (VRE) in a gel retardation assay. Three specific complexes were formed when nuclear extracts were prepared from estrogen agonist treated uteri or when ligand-free ER from cytosol was used. ER protein was associated with the three complexes, as demonstrated by their ability to bind anti-ER antibody H222. Specific complexes were formed only when double stranded nonheat-denatured VRE was used. Mutation of the ERE in VRE abolished specific binding. The complexes formed by nuclear extracts were qualitatively identical when obtained from mice treated with a variety of estrogenic compounds with different potencies. Nuclear extracts obtained from mice treated with an estrogen antagonist LY117018 formed complexes that migrated slower than the complexes formed by the other estrogenic compounds examined. The dissociation rates (k-1) and equilibrium dissociation constants (Kd) of the ER-VRE complexes formed by estradiol- or estriol-bound ER or ligand-free ER were measured and were found to be very similar, although the ligand-free specific ER complexes associate and dissociate less rapidly than those of estradiol- or estriol-bound ER. In addition, one of the specific complexes formed by the estriol nuclear extract dissociated more slowly than the equivalent estradiol complex. Heat activating ligand-free ER did not increase its binding to VRE. It appears that the ligand binding domain of the ER does not exert its regulatory effects at the level of sequence-specific DNA binding, since its occupancy does not alter binding to the ERE. The subtle differences we observed in association and dissociation of multiple complexes when unoccupied ER and ER bound to ligands of varying potencies are compared may reflect differences in ER association with other protein factors that govern transcriptional activity. PMID- 2330007 TI - Transcriptional analyses of steroid-regulated gene networks. AB - It has been proposed that cell-specific responses to steroid action are the result of coordinate expression of steroid gene networks. Using three different cell systems, we have performed transcriptional analyses to determine if the observed hormone-induced alterations in gene expression are consistent with a limited number of potential target genes in any one cell type. Our results indicate that greater than 95% of the transcripts in dexamethasone-treated rat hepatoma (HTC), or mouse lymphoma (WEH17) cells, are similar to the mRNAs in untreated cells based on subtraction hybridization. In addition, we find that although the castration-induced expression of androgen-regulated transcripts in the rat ventral prostate (RVP) is significantly different between normal and castrated rats (19%), the majority of these mRNAs are accounted for by the over abundance of sulfated glycoprotein-2 sequences. Specifically, analysis of an RVP subtracted cDNA library revealed that sulfated glycoprotein-2 mRNA masked the presence of less abundant differentially expressed sequences, confirming that the actual size of the RVP androgen gene network is small. We conclude that steroid mediated changes in transcription accurately reflect the expression of a few cell specific target genes, and thus support the model of steroid gene networks. The potential to characterize key elements which determine both the time course and magnitude of cell-specific hormone responses is discussed. PMID- 2330008 TI - Widespread organ expression of the rat proenkephalin gene during early postnatal development. AB - The opioid peptides have been implicated as potential regulators of cell development in nervous and reproductive tissues. A survey of proenkephalin gene expression during rat development showed that the mRNA for this opioid precursor is present at substantial concentrations in several developing tissues (kidney, liver, skin, skeletal muscle, and lung) that have essentially undetectable levels in adults. In neonatal rats, skeletal muscle has greater concentrations of this transcript than brain. Polysomal analysis further demonstrated that proenkephalin mRNA is actively translated in skeletal muscle from newborn rats. These results raise the possibility that proenkephalin and its products perform a general regulatory role in cell proliferation or differentiation. PMID- 2330010 TI - Aneuploidy induction in human fibroblasts: comparison with results in Syrian hamster fibroblasts. AB - The susceptibility of human fibroblast cells in culture to neoplastic transformation by chemical carcinogens is appreciably lower than that of rodent fibroblasts. We have proposed that a key step in the neoplastic progression of Syrian hamster embryo fibroblasts is the induction of aneuploidy by carcinogens. It is possible that the different sensitivity to neoplastic transformation of Syrian hamster versus human cells is due to a difference in genetic stability following treatment with chemicals inducing aneuploidy. Therefore, we measured the induction of numerical chromosome changes in normal human fibroblasts and Syrian hamster fibroblasts by 4 specific aneuploidogens. Dose- and time-dependent studies were performed. Nondisjunction, resulting in aneuploid cells with a near diploid chromosome number, in up to 14-28% of the hamster cells was induced by colcemid (0.1 microgram/ml), vincristine (30 ng/ml), diethylstilbestrol (DES) (1 microgram/ml) or 17 beta-estradiol (10 micrograms/ml). In contrast, human cells displayed far fewer aneuploid (near-diploid) cells, i.e., 8% following treatment with colcemid (0.02 micrograms/ml) or vincristine (10 ng/ml) and only 3% following treatment with DES (6 micrograms/ml) or 17 beta-estradiol (20 micrograms/ml). The doses at which the maximum effect was observed are given. Treatment of human cells induced a higher incidence of cells with a near tetraploid chromosome number, which was similar to the level observed in treated hamster cells except at the highest doses. These results indicate that human cells respond differently from hamster cells to agents that induce aneuploidy. In particular, nondisjunction yielding aneuploid human fibroblasts with a near diploid chromosome number was less frequent. The magnitude of the observed species differences varied with different chemicals. The difference in aneuploidy induction may contribute, in part, to species differences in susceptibility of fibroblasts to neoplastic transformation. PMID- 2330009 TI - Glucocorticoid-dependent maturation of mouse mammary tumor virus glycoproteins in mouse lymphoma cells: isolation of variants with constitutive viral protein maturation and normal glucocorticoid receptor function. AB - The posttranslational maturation and cell surface localization of mouse mammary tumor virus (MMTV) envelope glycoproteins is regulated by glucocorticoid hormone in mouse T-lymphoma cell line W7MG1. Only when the cells are cultured with glucocorticoid is the MMTV envelope precursor, Pr74, converted efficiently to the two mature proteolytic products, gp52 and gp33. By immunological selection we have isolated protein-processing variants that express the mature viral proteins constitutively on the cell surface. The rate of synthesis of Pr74 is indistinguishable in variant and wild-type cells, but the variants efficiently convert Pr74 to gp52 and gp33 even when grown without the hormone. The variant phenotype persists when the variant cells are fused with uninfected wild-type cells to form somatic cell hybrids, indicating that the variant phenotype resulted from expression of a new or altered function that is not expressed in wild-type cells grown without glucocorticoid. Although the specific gene whose structure or regulation is altered in the variant has not yet been determined, some possibilities have been eliminated. First, the number and function of the glucocorticoid receptors in the variant cells was normal, suggesting that alterations in this protein were not responsible for the variant phenotype. Second, comparison by two-dimensional gel electrophoresis of gp52 produced in variant and wild-type cells revealed no differences in size or charge, indicating no gross differences in the processing of the viral proteins in the variant and wild-type cells. PMID- 2330011 TI - Analysis of cytogenetic effects in bone-marrow cells of rats subchronically exposed to smoke from cigarettes which burn or only heat tobacco. AB - The genotoxic effects of 90-day nose-only exposures to smoke from new cigarettes, which heat but do not burn tobacco (New), or from reference cigarettes, which burn tobacco, were evaluated in Sprague-Dawley rats by examining the cytogenetic endpoints of sister-chromatid exchanges (SCE), chromosome aberrations, and micronuclei in bone-marrow cells. The concentrations of wet total particulate matter (WTPM) and carbon monoxide in the smoke from both cigarette types were similar. The mainstream smoke from both New and reference cigarettes was adjusted to WTPM concentrations of approx. 200 and 400 micrograms/l for low and high smoke exposure. Rats were exposed to smoke 1 h per day, 5 days per week for 13 consecutive weeks. Inhalation of smoke by the exposed animals was confirmed by analysis of blood carboxyhemoglobin and plasma nicotine. Examination of bone marrow cells following the final day of exposure showed that smoke from neither the New nor reference cigarette induced a positive response in the SCE, chromosome aberration, or micronucleus assays in rats. PMID- 2330012 TI - Acute cytogenetic effects of tyramine, MTCAs, NaCl and soy sauce on rat bone marrow cells in vivo. AB - The acute cytogenetic effects of tyramine and MTCAs, precursors of the mutagen present in soy sauce, were studied with the in vivo chromosome aberration test in rat bone marrow cells. The chemicals were administered intraperitoneally. Statistically significant positive results were obtained with tyramine at a dose of 5 mmole/kg (686 mg/kg) body weight and with MTCAs at doses over 0.50 mmole/kg (115 mg/kg) body weight, respectively. Chromosome aberrations (CA) induced by L proline co-administered with either tyramine or MTCAs were significantly lower than those induced by each chemical alone. These data suggest that L-proline, after endogenous nitrosation, became nitrosoproline and suppressed CA, and that, as a result of in vivo nitrosation of tyramine and MTCAs, they became mutagenic nitroso compounds showing positive results. Statistically significant positive results were obtained by administration of 40 mmole NaCl/kg body weight (2338 mg/kg). The cocarcinogenic role of NaCl with tyramine was suggested because soy sauce contains about 18% NaCl. PMID- 2330013 TI - Chromosome aberrations and urinary thioethers in smokers. AB - Chromosome aberrations, classified as chromosome- and chromatid-type aberrations, were evaluated in 94 individuals. The concentration of thioethers in the urine was also determined. The sample consisted of 41 non-smokers (control group) and 53 smokers, 25 smoked 10-20 cigarettes/day (subgroup IIA) and 28 smoked more than 20 cigarettes/day (subgroup IIB). Our aim was to perform internal dosimetry on smokers using a cytogenetic test, and a test for urinary excretion of thioethers, in order to determine the relation between these 2 methods of dosimetry. Our results show a higher frequency of chromosome aberrations (p less than 0.0001) and a higher excretion of urinary thioethers (p less than 0.0001) in smokers as compared to non-smokers. However, linear regression between these parameters was not statistically significant. In view of the variation between different individuals with regard to the amount of urinary thioethers, it seems more accurate to perform the biomonitoring of smoking by analyzing chromosome aberrations. PMID- 2330014 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 20-1990. A 16-year-old boy with a lesion of the left frontal lobe. PMID- 2330015 TI - Quantitation of human immunodeficiency virus in the blood. PMID- 2330016 TI - Interferon alfa-induced cardiac dysfunction. PMID- 2330017 TI - Familial Cushing's syndrome ("Carney complex") PMID- 2330018 TI - Treatment of mycosis fungoides. PMID- 2330019 TI - Colonoscopy in the management of upper respiratory infection. PMID- 2330020 TI - Hospital characteristics and mortality rates. PMID- 2330022 TI - Nintendinitis. PMID- 2330021 TI - Nintendo epilepsy. PMID- 2330023 TI - Half-hearted war on drugs. PMID- 2330024 TI - Embryo research. PMID- 2330026 TI - AIDS conferences. US eases controversial visa restrictions. PMID- 2330025 TI - Pressure stepped up on embryo research. PMID- 2330027 TI - The jaws of lactoferrin. PMID- 2330028 TI - Feature-blind grammar and dysphagia. PMID- 2330029 TI - Nonlinear forecasting as a way of distinguishing chaos from measurement error in time series. AB - An approach is presented for making short-term predictions about the trajectories of chaotic dynamical systems. The method is applied to data on measles, chickenpox, and marine phytoplankton populations, to show how apparent noise associated with deterministic chaos can be distinguished from sampling error and other sources of externally induced environmental noise. PMID- 2330030 TI - Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. AB - Over 200 recessive X chromosome-linked diseases, typically affecting only hemizygous males, have been identified. In many of these, prenatal diagnosis is possible by chorion villus sampling (CVS) or amniocentesis, followed by cytogenetic, biochemical or molecular analysis of the cells recovered from the conceptus. In others, the only alternative is to determine the sex of the fetus. If the fetus is affected by the defect or is male, abortion can be offered. Diagnosis of genetic defects in preimplantation embryos would allow those unaffected to be identified and transferred to the uterus. Here we report the first established pregnancies using this procedure, in two couples known to be at risk of transmitting adrenoleukodystrophy and X-linked mental retardation. Two female embryos were transferred after in vitro fertilization (IVF), biopsy of a single cell at the six- to eight-cell stage, and sexing by DNA amplification of a Y chromosome-specific repeat sequence. Both women are confirmed as carrying normal female twins. PMID- 2330031 TI - Symbiotic host-specificity of Rhizobium meliloti is determined by a sulphated and acylated glucosamine oligosaccharide signal. AB - Rhizobia are symbiotic bacteria that elicit the formation on leguminous plants of specialized organs, root nodules, in which they fix nitrogen. In various Rhizobium species, such as R. leguminosarum and R. meliloti, common and host specific nodulation (nod) genes have been identified which determine infection and nodulation of specific hosts. Common nodABC genes as well as host-specific nodH and nodQ genes were shown recently, using bioassays, to be involved in the production of extracellular Nod signals. Using R. meliloti strains overproducing symbiotic Nod factors, we have purified the major alfalfa-specific signal, NodRm 1, by gel permeation, ion exchange and C18 reverse-phase high performance liquid chromatography. From mass spectrometry, nuclear magnetic resonance, (35)S labelling and chemical modification studies, NodRm-1 was shown to be a sulphated beta-1,4-tetrasaccharide of D-glucosamine (Mr 1,102) in which three amino groups were acetylated and one was acylated with a C16 bis-unsaturated fatty acid. This purified Nod signal specifically elicited root hair deformation on the homologous host when added in nanomolar concentration. PMID- 2330032 TI - Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins. AB - Proteins of the transferrin family, which contains serum transferrin and lactoferrin, control iron levels in higher animals through their very tight (Kapp approximately 10(20)) but reversible binding of iron. These bilobate molecules have two binding sites, one per lobe, each housing one Fe3+ and the synergistic CO3(2-) ion. Crystallographic studies of human lactoferrin and rabbit serum transferrin in their iron-bound forms have characterized their binding sites and protein structure. Physical studies show that a substantial conformational change accompanies iron binding and release. We have addressed this phenomenon through crystal structure analysis of human apolactoferrin at 2.8 A resolution. In this structure the N-lobe binding cleft is wide open, following a domain rotation of 53 degrees, mediated by the pivoting of two helices and flexing of two interdomain polypeptide strands. Remarkably, the C-lobe cleft is closed, but unliganded. These observations have implications for transferrin function and for binding proteins in general. PMID- 2330033 TI - Relaxation of a transfer RNA specificity by removal of modified nucleotides. AB - The molecular recognition of specific transfer RNAs by the appropriate aminoacyl tRNA synthetase is an important step in determining the accuracy of translation of the genetic message from nucleic acids into proteins. Recent studies using variant tRNAs with specific sequence modifications have indicated particular regions that determine their identity. Here we consider whether the base modifications commonly found in tRNAs contribute to their identity. Although unmodified tRNA(Asp) is charged with aspartate as efficiently as the modified native tRNA, it is mischarged with arginine with considerably increased efficiency. Our results indicate that post-transcriptional modification of tRNAs introduces structural 'anti-determinants', restricting the efficiency with which the tRNAs are charged with inappropriate amino acids. PMID- 2330034 TI - Biotechnology patent disputes. Amgen plays for time. PMID- 2330035 TI - Biotechnology patent disputes. Market machinations. PMID- 2330036 TI - AIDS research funding. Budget division disputed. PMID- 2330037 TI - Animal research. White House says no. PMID- 2330039 TI - Time for cigarette reclassification? PMID- 2330038 TI - DNA fingerprinting. Mapping 'frozen accidents'. PMID- 2330040 TI - Radiation and exposure rate. PMID- 2330041 TI - Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins. AB - The eukaryotic upstream binding factor (UBF), recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the species-specific factor, SL1. Isolation of complementary DNA clones and sequence analysis reveals similarities between DNA binding domains of human UBF (hUBF) and high mobility group (HMG) protein 1. Expression, cellular localization and in vitro transcription studies establish that cloned hUBF encodes a nucleolar factor that binds specifically to the upstream control element and core of the rRNA gene promoter to activate transcription in a binding site-dependent manner. PMID- 2330042 TI - A cholecystokinin-like hormone activates a feeding-related neural circuit in lobster. AB - The peptide hormone cholecystokinin (CCK) contributes to the production of feeding-related behaviour in mammals, but the mechanism by which it exerts its effects remains unclear. The gastric mill neural circuit of lobster is an experimentally accessible model system for studying the hormonal control of feeding-related behaviour. Composed of 11 identified neurons, this circuit produces rhythmic movement of teeth within the stomach. We have previously shown that the gastric mill motor pattern can be modulated by a cholecystokinin-like peptide in vitro. We report here that (1) after feeding, levels of CCK-like peptide in haemolymph increase with the activation of the gastric mill, (2) injections of CCK activate the gastric mill, and (3) a specific CCK antagonist inhibits feeding-induced gastric mill activity. This neatly demonstrates a casual link between in vivo release of a peptide hormone and activation of a neural circuit. PMID- 2330043 TI - Activin is a nerve cell survival molecule. AB - The structures of five neurotrophic molecules have so far been published. Nerve growth factor, fibroblast growth factor and purpurin, have been identified as nerve-cell survival molecules. More recently, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor have been cloned and sequenced. As all these proteins stimulate the survival of ciliary or sensory neurons, a new cell survival assay is required if novel neurotrophic molecules are to be discovered. P19 teratoma cells differentiate to nerve-like cells in the presence of 5 x 10( 7) M retinoic acid (RA). But when P19 cells are plated in N2 synthetic medium without being exposed to RA, they die within 48 h. In an attempt to identify a molecule(s) that can substitute for RA in promoting P19 survival, we assayed serum-free growth-conditioned media for their ability to promote P19 survival. One cell line from the rat eye secreted a molecule that promoted the survival of P19 cells and some types of nerve cell. We identified this molecule as activin, better known for its role in hormone secretion. PMID- 2330044 TI - Missing link at Sellafield. PMID- 2330045 TI - Cooperating molecules in biology. PMID- 2330046 TI - Gardner report. Leukaemia and radiation. PMID- 2330047 TI - Myelination in severed nerves. PMID- 2330048 TI - To flow or not to flow? PMID- 2330050 TI - Radon scare doubted. PMID- 2330049 TI - The three-dimensional structure of the bacterial virus MS2. AB - The structure of the icosahedral bacteriophage MS2 has been determined to 3.3 A resolution by X-ray crystallography. The phase determination involved both molecular replacement at low resolution using a known structure and heavy-atom substitution. The coat protein has no structural similarity to that of any other known RNA virus. PMID- 2330051 TI - AIDS testing. Postal tests on the way. PMID- 2330052 TI - Drug legislation. Drug companies divided. PMID- 2330054 TI - Abortion. RU486 under attack. PMID- 2330053 TI - Genetic diversity in Sargasso Sea bacterioplankton. AB - Bacterioplankton are recognized as important agents of biogeochemical change in marine ecosystems, yet relatively little is known about the species that make up these communities. Uncertainties about the genetic structure and diversity of natural bacterioplankton populations stem from the traditional difficulties associated with microbial cultivation techniques. Discrepancies between direct counts and plate counts are typically several orders of magnitude, raising doubts as to whether cultivated marine bacteria are actually representative of dominant planktonic species. We have phylogenetically analysed clone libraries of eubacterial 16S ribosomal RNA genes amplified from natural populations of Sargasso Sea picoplankton by the polymerase chain reaction. The analysis indicates the presence of a novel microbial group, the SAR11 cluster, which appears to be a significant component of this oligotrophic bacterioplankton community. A second cluster of lineages related to the oxygenic phototrophs- cyanobacteria, prochlorophytes and chloroplasts--was also observed. However, none of the genes matched the small subunit rRNA sequences of cultivated marine cyanobacteria from similar habitats. The diversity of 16S rRNA genes observed within the clusters suggests that these bacterioplankton may be consortia of independent lineages sharing surprisingly distant common ancestors. PMID- 2330055 TI - Embryo research. Pro-life actions backfire. PMID- 2330056 TI - A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. AB - Growth factors are thought to function as pivotal autocrine-paracrine regulatory signals during embryonic development. Insulin-like growth factor II (IGF-II), a mitogenic polypeptide for a variety of cell lines, could have such a role, as indicated by the pattern of expression of its gene during rodent development. The IGF-II gene uses at least three promoters and expresses several transcripts in many tissues during the embryonic and neonatal periods, whereas expression in adult animals is confined to the choroid plexus and the leptomeninges. To examine the developmental role of IGF-II, we have begun to study the consequences of introducing mutations at the IGF-II gene locus in the mouse germ line. We have disrupted one of the IGF-II alleles in cultured mouse embryonic stem (ES) cells by gene targeting and constructed chimaeric animals. Germ-line transmission of the inactivated IGF-II gene from male chimaeras yielded heterozygous progeny that were smaller than their ES cell-derived wild-type littermates (about 60% of normal body weight). These growth-deficient animals were otherwise apparently normal and fertile. The effect of the mutation was exerted during the embryonic period. These results provide the first direct evidence for a physiological role of IGF-II in embryonic growth. PMID- 2330057 TI - Ancestral lysozymes reconstructed, neutrality tested, and thermostability linked to hydrocarbon packing. AB - The controversy surrounding the idea that neutral mutations dominate protein evolution is attributable in part to the inadequacy of the tools available to evolutionary investigators. With a few exceptions, most investigations into the force driving protein evolution have relied on indirect criteria for distinguishing neutral and non-neutral variants. To investigate a particular pathway of molecular evolution, we have reconstructed by site-directed mutagenesis likely ancestral variants of the lysozymes of modern game birds (order Galliformes), tested their activity and thermostability and determined their three-dimensional structure. We focused on amino acids at three positions that are occupied in all known game birds either by the triplet Thr 40, Ile 55, Ser 91, or by the triplet Ser 40, Val 55, Thr 91. We have synthesized proteins representing intermediates along the possible three-step evolutionary pathways between these triplets. Although all of these are active and stable, none of these intermediates is found in known lysozymes. A comparison of the structures and thermostabilities of the variants reveals a linear correlation between the side-chain volume of the triplet and the thermostability of the protein. Each pathway connecting the two extant triplet sequences includes a variant with a thermostability outside the range of the extant proteins. This observation is consistent with a non-neutral evolutionary pathway. The existence of variants that are more stable than the extant proteins suggests that selection for maximum thermostability may not have been an important factor in the evolution of this enzyme. PMID- 2330058 TI - Human frontier science program. Turned back at the door. PMID- 2330059 TI - Case management in rural areas: definition, clients, financing, staffing, & service delivery issues. AB - Case management is one method for helping persons obtain needed health and social services while maximizing available community resources. How do needed case management services differ between rural and urban areas? PMID- 2330060 TI - Relationship between nursing work load and turnover. AB - This survey of 123 medical-surgical nurses revealed that full-time status, large hospital size, and large unit size were associated with higher role overload and nurses' intent to leave their jobs. PMID- 2330062 TI - Technology assessment in reducing costs and improving care. PMID- 2330061 TI - The next revolution. PMID- 2330063 TI - To manage by power or influence--the nurse manager's choice. PMID- 2330064 TI - Self-study module for mandatory AIDS education. PMID- 2330065 TI - Health care in rural America: a view from the nation's capital. AB - While the nation's health care system has been the subject of significant attention, the needs of rural Americans and the adequacy of their health care delivery system have been largely overlooked. By considering the unique features of rural America, appropriate delivery models can be developed. PMID- 2330066 TI - Participation of nurse executives in product decisions. AB - This national survey of 30 chief nurse executives documented the significant product purchase power of these administrators. While nurse executives in small organizations tended to be involved in almost all product decisions, nurse executives in larger institutions focused on major hospital equipment purchases. PMID- 2330067 TI - Case-control study of neuroepithelial tumors in Rochester, Minnesota, 1950-1977. AB - Rochester, Minnesota, has over many decades the highest reported incidence rates of primary intracranial neoplasms. This occurs in the absence of any readily identifiable risk factors. A case-control study of neuroepithelial tumors has been undertaken utilizing the records-linkage system at the Mayo Clinic. This study failed to yield any significant findings for the factors examined. PMID- 2330068 TI - A cluster classification for histologic diagnoses of CNS tumors in an epidemiologic study. AB - This paper introduces a method which was utilized to sort multiple pathologic diagnoses pertaining to brain tumors into clusters of equivalent diagnostic terms for an epidemiological study of brain cancer. The method enabled the medical record abstractors to ascertain cases for the study. It enabled the reviewing pathologist to identify differences between original and reviewed diagnoses. It identified the large range of classification systems of brain tumors used by practicing pathologists as a factor contributing to confusion of data if slide reviews are not incorporated into epidemiological studies, and demonstrated how the use of a cluster classification alleviates this problem. PMID- 2330069 TI - Neurological examination in subjects over 65 years: an epidemiological survey. AB - The frequency of abnormal findings at neurological examination was analyzed in an unselected sample of elderly people aged 67-87 years. Absent deep tendon reflexes and impairment of proprioceptive sensation rarely occurred in the elderly. Limitation of upward gaze and convergence appear a common finding, especially in the very old. Overall, the presence of cortical disinhibition signs (primitive reflexes and paratonia) did not discriminate well between subjects without CNS disease and demented patients. Only the presence of a prominent and persistent response to the stimulus and the number of cortical disinhibition signs found in the same subject appear useful criteria to distinguish between normality and dementia. PMID- 2330070 TI - Clinical and epidemiological aspects of Alzheimer's disease with presenile onset: a case control study. AB - Little is known regarding the pathogenetic factors for Alzheimer's disease (AD). We studied 63 AD patients in order to evaluate if there were clinical subtypes of AD and whether prior illnesses and life-styles were involved in the development of the disease. In our patients selected for onset of symptoms before age 65 we did not find any significant clinical heterogeneity. Furthermore, we found no data in the medical history that are predictive for the development of presenile AD but observed a significantly increased frequency of dementia in the families of AD patients in comparison to controls. PMID- 2330071 TI - Specific reading disability in Egyptian children. Clinical picture, diagnosis and prognosis. AB - Forty-four elementary school children with average or above average intelligence were found to be 1-2 years behind the expected level of reading ability. They were left to proceed in their conventional education program for the next 3 years. Reassessment revealed that 23 children (52%) had attained a normal reading level. 21 (48%) children remained unchanged. They were categorized into the corrective reading disability (CRD) and specific reading disability (SRD) groups, respectively. Clinical evaluation of both groups showed that children with SRD had a significantly higher incidence of: (1) illiteracy of both parents; (2) low sociocultural standard; (3) positive family history of elementary school failure; (4) abnormal optokinetic nystagmus; (5) disturbed homolateral dominance, and (6) immature EEG tracing over the occipital area. These findings could be of value in identifying high risk children for SRD. PMID- 2330072 TI - Sites in the brain at which cholecystokinin octapeptide (CCK-8) acts to suppress feeding in rats: a mapping study. AB - In this study, an examination was made of the sites in the brain of the rat at which the injection of cholecystokinin octapeptide (CCK-8) would alter food intake. Rats fasted for 24 hr received intracerebral injections of CCK-8 (1 nmol) or an equal volume of saline (0.5 microliters), into various sites in the brain through permanently implanted stainless steel cannulae. After prior acclimatisation to individual plexiglass compartments, latency to feed, as well as consumption of food and water during 0-20, 20-40 and 40-60 min after the injection, were recorded. The available food was the standard rat pellets, to which the animal otherwise had constant daily access. With this paradigm, active sites at which CCK-8 suppressed feeding were defined as sites at which consumption of food for 0-20 min was reduced by 25% or more, or the latency to feed was increased by 3 min or more after the injection of CCK-8, as compared to the effect of the injection of saline, made at the same site. Such active sites were most densely distributed in the rostral diencephalon, e.g. hypothalamus, the medial pontine area and lateral medulla, in the vicinity of the nucleus tractus solitarii (NTS). By grouping data for injections according to histologically identified sites, statistical analysis of groups of injections confirmed that these three major areas of the brain were active with regard to the suppression of feeding by CCK-8. These data suggest that CCK may not only initiate satiety messages, as a circulating hormone at peripheral sites, but also participate in the conduction of such information to the target in the brain by serving as a neurotransmitter in the lateral medulla (e.g. NTS), medial pontine area (e.g. relay station between the NTS and hypothalamus) and the lateral hypothalamus, where local release of CCK-8 after stomach loading has been observed. PMID- 2330073 TI - Acetylcholine release in vivo: effects of chronic treatment with monosialoganglioside GM1. AB - Rats with unilateral cortical devascularizing lesions were treated with the monosialoganglioside GM1 in two different ways. One group of animals received GM1 (5 mg/kg/day, for 7 days), through a permanent cannula implanted intracerebroventricularly (i.c.v.) and connected to an osmotic minipump. The other group was treated with microencapsulated GM1 placed directly onto the surface of the lesioned cortex. The effect of GM1, administered into the lateral ventricle and supracortically, on the release of ACh in vivo was studied, using a microdialysis system combined with sensitive high performance liquid chromatography (HPLC). The release of acetylcholine and choline was studied in the cortex and striatum of the rat under nonstimulated (basal) and KCl (100 mM) stimulating conditions. The non-stimulated release of acetylcholine was only measurable in the presence of neostigmine and was found to be about 30 microM in the cortex and approximately 10 times greater in the striatum. A large concentration of KCl led to a remarkable increase of acetylcholine in the control (C) and vehicle-treated lesioned groups (V i.c.v., V cap: 11-13 fold), but was greater in the GM1-treated groups (GM1 i.c.v., GM1 cap: 20-25 fold). In contrast, KCl-stimulated release of ACh in striata from GM1-treated lesioned groups was significantly less (5-10 fold), compared to the unlesioned controls (C: 16 fold) and lesioned vehicle-treated rats (V i.c.v. and V cap: 16-18 fold). The release of choline was not increased significantly by large concentrations of KCl present in the perfusion medium. In all experimental groups, and in both structures of the brain, ratios between stimulated and non-stimulated release of choline was between 0.7-1.2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330074 TI - Effect of irreversible loss of muscarinic receptors on (3H)-acetylcholine release from the hippocampus. AB - The role of muscarinic receptors in the regulation of (3H)-acetylcholine (3H-Ach) release from the hippocampus was investigated with the irreversible cholinergic agonist BM-123 (N-[4(2-chloroethylmethylamino)-2-butynyl]2-pyrrolidone). Pretreatment with BM-123 had no significant effect on spontaneous (3H)-Ach release at 12, 24, 72, and 144 hr. However, this treatment significantly reduced the inhibitory effect of oxotremorine (10 microM) on (3H)-Ach release at 12, 24, and 72 hr (p less than 0.02). At these time intervals, there was a significant loss in muscarinic receptors as determined by (3H)-oxotremorine-M binding. The maximum loss of both oxotremorine-induced inhibition of (3H)-Ach release and muscarinic receptors occurred at 12 hr. Both parameters returned to normal by 144 hr. There was a linear relationship between the recovery of (3H)-Ach release and (3H)-oxotremorine-M binding sites. These results indicate that muscarinic receptors play a significant role in the regulation of (3H)-Ach release in hippocampus, and that this receptor system may lack spare receptors. PMID- 2330075 TI - The cholinesterase inhibitor soman increases inositol trisphosphate in rat brain. AB - Studies were conducted to determine the effect of the cholinesterase inhibitor soman on the amount of inositol trisphosphate in the neocortex, striatum, cerebellum, and medulla-pons regions of rat brain in vivo. The studies indicate that treatment with soman increases inositol trisphosphate in the neocortex and striatum, but not in the cerebellum or medulla-pons region. In the neocortex the most pronounced increases were observed in animals with severe poisoning symptoms, however inositol trisphosphate was also found to be elevated in animals with only mild poisoning symptoms. PMID- 2330076 TI - Patterns of failure of aspirin treatment in symptomatic atherosclerotic carotid artery disease. AB - Over a 24-month period, 291 patients were consecutively admitted to the West Haven Veterans Administration Medical Center with new ischemic neurological symptoms. Of these, 90 patients (31%) developed ischemic neurological symptoms while taking aspirin (aspirin treatment failure). Of those in whom aspirin treatment failed, 66 patients had ischemic symptoms in the distribution of the carotid artery. Aspirin treatment failed in 21 patients with severe carotid stenosis (greater than 75% stenosis). Eleven of these 21 patients had cerebral infarctions while taking aspirin, and 7 of these 11 infarcts occurred without the prior warning of transient ischemic attacks. Aspirin treatment failed in 45 patients with lesser degrees of carotid stenosis. Transient ischemic attack without permanent ischemia was the most common manifestation of failure in these patients. Infarction occurred in only 12 of these 45 patients and in only 4 patients did infarction occur without warning. We conclude that patients with symptomatic high-grade carotid stenosis (greater than 75%) in whom aspirin treatment failed are likely to suffer an infarct without warning as the first sign of treatment failure (P less than 0.033). We suggest that this subgroup of patients should be considered for alternative forms of therapy. PMID- 2330077 TI - Surgical excision of cerebral arteriovenous malformations: late results. AB - A follow-up study of 153 consecutive patients who underwent complete excision of an angiographically visualized intracerebral arteriovenous malformation was conducted. The follow-up period ranged from 0.5 to 10.6 years, with a mean of 3.8 years. The presenting clinical event was hemorrhage in about one-half of the patients and seizure in about one-third. There was a marked tendency for postoperative neurological deficits to improve with time, so that whereas the immediate postoperative rate of serious morbidity was 24.2%, only 7.8% of the patients were found to have serious morbidity at follow-up. An additional 3 patients had died, one of an unrelated carcinoma, making the mortality related to arteriovenous malformation 1.3%. The classification of Spetzler and Martin (43) was used retrospectively; the percentages of Grade I (easiest) through Grade V (most difficult) lesions were 7.8%, 22.9%, 28.8%, 26.8%, and 13.8%, respectively. The early result was well correlated to grade, with good or excellent results in 100%, 94.3%, 88.6%, 61%, and 28.6% of the patients in Grades I through V, respectively. At follow-up, 98.7% of the patients with arteriovenous malformations of Grades I, II, and III were in good or excellent condition. The late morbidity and mortality rates for the patients in Grades IV and V were 12.2% and 38.4%, respectively. Of the patients who did not have seizures before surgery, 8.2% had only one or two seizures during the immediate postoperative period, and 7.1% had late seizures that were well controlled with medication in all. Of the patients who had seizures before surgery, over half were either cured or greatly improved with respect to the seizures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330078 TI - Social outcome related to cognitive performance and computed tomographic findings after surgery for a ruptured intracranial aneurysm. AB - A series of 83 patients was examined with a battery of cognitive tests, a clinical interview, and computed tomography 1 year after surgery for a ruptured intracranial aneurysm. Disability on the Glasgow Outcome Scale (33%), failure to return to work (25%), impaired social relations (25%), and subjective or clinical mental impairment (56%) were found to be related to each other and to poor performance on cognitive tests, especially to verbal impairments in patients with left lateral infarctions and to memory deficits and cognitive inflexibility in patients with frontal medial infarctions. Furthermore, cognitive deficits and poor outcome were associated with diffuse brain damage. Depression and anxiety were unrelated to test performances, but were frequently reported by patients with right lateral infarctions. PMID- 2330079 TI - Recurrent intracerebral hemorrhage due to hypertension. AB - We report a series of 14 patients who had recurrent intracerebral hemorrhage due to hypertension. These patients comprise 2.7% of all those admitted to the Soonchunhyang University Chonan Hospital for hypertensive intracerebral hemorrhage from 1985 to 1988. Women outnumbered men by 13 to 1. The mean age of the patients was 54.5 years at the time of the first hemorrhage and 55.4 years at the time of the second hemorrhage. The mean interval between attacks was 13.1 months. All patients were hypertensive on admission, and in 10 patients hypertension had been diagnosed previously. None of the patients had received regular antihypertensive therapy, even after the first hemorrhage. Hemiplegia was the most common deficit seen after both the first and second attacks. The site of the first hemorrhage was ganglionic in 9 patients, cerebellar in 3 patients, and lobar in 2 patients. The site of the second hemorrhage was ganglionic in 9 patients and lobar in 5. The site of recurrent hemorrhage was different from the initial site in all patients except one. The most common pattern of recurrence was "ganglionic-ganglionic." The "lobar-lobar" pattern was noted in only 1 patient. The hypertensive changes of the cerebral arteries are considered to be the major cause of these recurrent hemorrhages. We believe that recurrent intracerebral hemorrhages in hypertensive patients are not rare as previously thought. Possible reasons for the increased frequency of recurrent intracerebral hemorrhage are discussed. PMID- 2330080 TI - Hydrosyringomyelia associated with a Chiari I malformation in children and adolescents. AB - The clinical presentation, radiological features, and results of surgical treatment were analyzed in 17 cases of hydrosyringomyelia associated with a Chiari malformation, in children and adolescents younger than 20 years of age. The initial symptoms were a skeletal abnormality (71%), such as scoliosis (11 patients) or pes cavus (1 patient), pain or numbness (24%), and motor weakness (6%). Frequently seen signs on admission were sensory deficit (100%), scoliosis (85%), muscle weakness (64%), muscle atrophy (35%), and lower cranial nerve palsy (35%). The characteristic neurological findings were unilateral sensory and motor deficits (65%) with decreased or absent deep tendon reflexes on the same side. The localization of the syrinx on the axial section varied according to the level, even in the same patient. In 11 patients with unilateral sensory disturbances or unilateral sensory and motor deficits, the syrinx was located in the region corresponding to the posterolateral portion on the same side as that of sensory disturbance at the cervical or thoracic level. On the other hand, in 6 patients with bilateral sensory and motor deficits, the syrinx was located in the central portion and extended into the posterolateral portion of the more affected side. A syringosubarachnoid shunt was placed in 16 patients, foramen magnum decompression without closure of the obex was performed in 1 patient, ventriculoperitoneal shunt in 1 patient, terminal syringostomy in 1 patient, and foramen magnum decompression with terminal syringostomy in 1 patient. In 15 of 17 patients (88%), the neurological symptoms improved after an average follow-up of 4 years and 1 month. We think that as a surgical treatment, placement of a syringosubarachnoid shunt is effective. PMID- 2330081 TI - Growth of human schwannomas in the subrenal capsule of the nude mouse. AB - To develop a reproducible in vivo model for the growth of human schwannomas we implanted tumor specimens from 14 different patients (13 acoustic neurinomas; 1 trigeminal schwannoma) into the subrenal capsule of 108 nude mice. In 11 experiments, the animals were implanted with only solid tumor from the surgical specimens. In two experiments, the tumor implants were made from solid tumors and cell clusters. In one experiment, the tumor implants were made from cell clusters alone. The size and neovascularization of these tumors were serially determined during a 1.5- to 3-month period. The percentages of tumors that survived or grew were 77.3% from solid tumors and 70% from cell clusters. Maximum tumor volume varied as did the time span to reach that volume. Tumor enlargement and stability correlated well with neovascularity; regressing tumor showed minimal or no neovascularity. Histological analysis of the implanted tumors showed spindle cells that are similar to the original tumor. Immunohistochemical staining for S100 demonstrated the Schwann cell nature of the implants. Analysis of genomic DNA from an acoustic neurinoma that had been implanted for 3 weeks was consistent with its human origin. There were no significant microscopic differences among groups receiving solid tumor implants or cell clusters. These studies suggest that implantation of human schwannomas into the subrenal capsule of the nude mouse is a reproducible method to study tumor growth that may be useful in testing potential therapeutic regimens or genetic modulation of schwannomas. PMID- 2330082 TI - Operative treatment of intracranial epidermoid cysts and cholesterol granulomas: report of 21 cases. AB - Thirteen patients had operations to remove intracranial epidermoid cysts, and long-term follow-up was obtained. Total or nearly total tumor and capsule removal was accomplished in 7 patients during the initial operation. This group required no additional operations. The other 6 underwent subtotal tumor removal and required multiple operations for symptomatic tumor recurrence. This latter group had a poorer neurological outcome. We conclude that initial total or near-total tumor resection is highly desirable in treating intracranial epidermoid cysts, particularly in physiologically young individuals. Five patients were followed after operations to remove pure cholesterol granulomas of the petroclival bone, and 3 additional patients were followed after operations to remove tumors with combined histopathological features of both an epidermoid cyst and cholesterol granuloma. Four patients with some component of a cholesterol granuloma had concurrent middle ear infections, and 4 did not. Intracranial subtotal excision and drainage of these lesions was the initial operative management in 7 patients, 5 of whom have required multiple operations for symptomatic tumor recurrence. Therefore, we conclude that subtotal excisional procedures for tumors with histopathological features of cholesterol granulomas are not usually successful in establishing long-term cures. Total excision, as recommended for epidermoid cysts, tumors frequently confused with cholesterol granulomas when occupying the petroclival region, may be warranted for these tumors as well. We postulate that when a congenital epidermoid cyst occurs in the petroclival bone, it may incite a local inflammatory reaction, producing lesions which have the histological features of both epidermoid cysts and cholesterol granulomas. PMID- 2330083 TI - Metabolic and hemodynamic aspects of peritumoral low-density areas in human brain tumor. AB - With the use of positron emission tomography, regional cerebral blood flow, oxygen utilization, and glucose utilization were measured in the peritumoral low density areas on x-ray computed tomographic images in 23 patients with supratentorial brain tumors: 7 meningiomas, 11 malignant gliomas, and 5 metastatic brain tumors. Findings on positron emission tomography in these areas revealed characteristic patterns associated with the types of tumor and the degree of mass effect. It is likely that two different types of pathophysiological states exist in "peritumoral edema": 1) primary ischemia caused by mechanical compression by the tumor mass in meningiomas; and 2) primary metabolic suppression (mainly in oxygen metabolism) in malignant brain tumors. PMID- 2330085 TI - The value of computed tomographic scans in patients with low-risk head injuries. AB - The determination that a particular head injury is "mild" or "low-risk" is usually made on clinical grounds. Observation at home or in the hospital has been the usual treatment for such patients. A recent report of excessive mortality among these patients with low-risk head injuries in some hospital settings suggests the need for improvement in diagnostic criteria. Our study included 658 patients admitted to Cooper Hospital for a mild head injury, who had a Glasgow Coma Scale score of 13 to 15 on admission, and who experienced a brief loss of consciousness or amnesia after the injury. Their records and cranial computed tomographic (CT) scans on admission were reviewed to determine their subsequent course. In 18% of patients abnormalities were seen on the initial CT scan and 5% required surgery. Among the 62 patients with a Glasgow Coma Scale score of 13, 40% had abnormalities on the CT scan and 10% required surgery. None of the 542 patients with normal CT scans on admission showed subsequent deterioration and none needed surgery. These figures suggest that history and physical examination alone are not adequate to assess head injury or severity of risk and that the addition of a CT scan greatly improves patient assessment. Abnormalities on CT scans are so common in patients with a Glasgow Coma Scale score of 13 that head injuries in these patients should be classified as "moderate" rather than "mild" in severity and risk. Patients with normal CT scans should be considered for observation at home, allowing hospital personnel to devote full attention to the more seriously injured patients. PMID- 2330084 TI - C6 glioma cell invasion and migration of rat brain after neural homografting: ultrastructure. AB - C6 tumor cells (10(6] were grafted as suspensions into freshly made implantation pockets in rat host cerebral cortex. Specimens were prepared for transmission and scanning electron microscopy 1 to 7 days postimplantation (DPI). By 3 DPI vacuolated C6 cells had migrated on or invaded the host brain. C6 cells were observed on the glia limitans on the surface of the brain, in the corpus callosum, subependymal space, and perivascular space and had invaded the cortex under the implantation pocket. In addition to the tumor mass that was observed under the implantation pocket, by 7 DPI individual C6 cells had migrated into the corpus callosum and internal capsule. Migrated C6 cells were observed in a perineuronal position in the hippocampus and other gray matter structures inferior to the corpus callosum. Micropockets were found around each C6 cell and the processes of these cells had replaced host parenchyma. The preferred routes of migration were on basal lamina and parallel and intersecting nerve fiber bundles. Invasion occurred through gray and white matter. The movement of homografted C6 cells in the brain suggests that these cells actively migrate as individual cells in addition to invading as a mass. PMID- 2330086 TI - Microsurgery of midbrain lesions. AB - Of 41 patients with midbrain lesions, 25 underwent definitive surgical exploration. In 16 patients surgical exploration was not warranted, since the patients had only slight neurological deficits and longstanding histories or consent was not given. The infratentorial supracerebellar approach proved to be the ideal method of exposure in 20 patients, in whom the lesion was located in the more dorsal aspect of the midbrain. In 6 of these patients the mass lesion extended from the cerebellum into the midbrain and, therefore, a transcerebellar route was also needed for exposure. In 5 patients the subtemporal approach was chosen. Three patients died as a result of the operation, but in the other 22 patients no increase in morbidity after surgery was apparent and the immediate postoperative course was normal. Five patients with malignant tumors died from recurrence despite radiotherapy. The remaining 17 patients have been doing well up to 14 years after surgery, but 3 had only limited follow-up. This experience with surgical exploration and total resection or evacuation of midbrain lesions in 25 patients should prove the safety of modern microsurgical techniques. Emphasis is placed on the benefit of microtopographic considerations in the choice of the most suitable approach to these deep-seated lesions. PMID- 2330087 TI - Use of Vicryl (polyglactin 910) mesh to limit epidural scar formation after laminectomy. AB - A variety of substances have been used at laminectomy sites to prevent postoperative epidural scarring. Free grafts of autologous subcutaneous fat are commonly used both clinically and experimentally. The free fat grafts usually survive, but decrease in size by about 50%. Postoperatively, subcutaneous seroma has been observed with the use of fat grafts, as well as recurrent symptoms of neural compression by the graft that required additional operations. When compared to the use of free grafts after laminectomy in dogs, Vicryl mesh produced slightly more scarring, but consistently less than that observed in control animals. The Vicryl mesh was resorbed by a minimal chronic inflammatory response over about 45 days. Seven of 11 fat-grafted zones showed signs of necrosis, at times with a greater collection of inflammatory cells than that associated with the Vicryl mesh. Of the 4 fat-grafted zones that showed good survival, 2 had gross evidence of neural compression. No surgical zone treated with Vicryl mesh exhibited evidence of neural compression. In view of these results, the use of Vicryl mesh at laminectomy sites may be a safer method of limiting postoperative epidural scar formation. PMID- 2330088 TI - Communicating hydrocephalus in adults: prediction of outcome after ventricular shunting procedures. AB - A series of adult patients with idiopathic hydrocephalus in whom shunts were placed are presented. Preoperative diagnostic and prognostic criteria were evaluated. Findings on computed tomographic scans (significant ventricular enlargement, the absence of gyral atrophy, and the absence of sylvian fissure enlargement) and the clinical triad associated with hydrocephalus in adults (dementia, ataxia, and especially incontinence of urine) all contributed individually and in combination to the diagnosis of hydrocephalus that could be corrected by surgery. The use of radionucleotide cisternography did not add any additional information. Its use as a diagnostic or prognostic aid is, therefore, suspect. The use of high-pressure shunting systems for the initial shunting procedure is emphasized. PMID- 2330089 TI - Pseudopsychopathic syndrome in hydrocephalus: a case report and review. AB - A 24-year-old man with a head injury developed a communicating hydrocephalus and underwent ventriculoperitoneal shunting. A revision was required, and the patient emerged from coma with severe behavior outbursts, which persisted for more than 1 year. Computed tomographic scans indicated a recurrence of low-pressure communicating hydrocephalus and a shunt revision was performed. The patient's severe behavior outbursts immediately decreased dramatically. The improvement continued long term and extended beyond the acute rehabilitation program. PMID- 2330090 TI - Unilateral hydrocephalus caused by an intraventricular venous malformation obstructing the foramen of Monro. AB - Unilateral hydrocephalus in an adult was caused by obstruction of the left foramen of Monro by an intraventricular venous malformation. Magnetic resonance imaging of the region of the foramen of Monro demonstrated the lesion, which subsequently was confirmed to be a venous malformation by angiography and surgery. PMID- 2330091 TI - Posttraumatic ligamentous disruption of the cervical spine, an easily overlooked diagnosis: presentation of three cases. AB - Three patients with hyperflexion sprain of the cervical spine secondary to motor vehicle accidents are discussed. One patient exhibited tetraplegia and the other two only had paresthesia of the upper and/or lower extremities at the scene of the accident. All patients were young with no evidence of degenerative disc disease or osteoarthritis. Diagnosis of hyperflexion sprain is suggested by transient or persistent neurological deficits, local tenderness, or plain film findings, which include interspinous fanning, localized kyphotic angulation, subluxation, or disc space narrowing. Review of our patients' records revealed that some of these findings were evident at their initial presentation. In patients who have no neurological deficits, controlled flexion and extension views after routine plain films may be diagnostic of an unstable cervical spine. If there is a persistent neurological deficit, a magnetic resonance imaging scan is the examination of choice. If there is no compression of the thecal sac or spinal cord, supervised flexion and extension views of cervical spine should be done. Definitive management of the unstable spine is operative fixation. PMID- 2330092 TI - Spinal cord compression secondary to idiopathic retroperitoneal fibrosis. AB - Retroperitoneal fibrosis is a rare disorder in which the abnormal fibrotic tissue compresses retroperitoneal organs. In the majority of patients no obvious cause can be found, hence the name idiopathic retroperitoneal fibrosis. The process can also arise from other anatomic areas, suggesting a multifocal origin. We report a case of dorsal epidural compression in a 63-year-old patient harboring idiopathic retroperitoneal fibrosis. A magnetic resonance imaging scan revealed the precise location of the lesion. It is suggested that retroperitoneal fibrosis should be considered in the differential diagnosis of epidural spinal cord compression. PMID- 2330093 TI - Chondroma of the lumbar spine, a rare cause of sciatica: case report. AB - A case of chondroma of the lumbar spine causing nerve root compression is presented. This benign tumor was completely removed, resulting in relief of all radicular symptoms. PMID- 2330094 TI - Testicular germ cell tumor with pineal metastases. AB - A patient with a mixed testicular germ cell tumor (choriocarcinoma, teratocarcinoma and embryonal carcinoma) that had metastasized to the lungs, cerebrum, and pineal gland is presented. The metastases had resulted in localized neurological signs and initially, on clinical grounds, a primary intracranial lesion could not be excluded. The occurrence of tumor metastases to the pineal gland is discussed and the literature is reviewed. PMID- 2330095 TI - Enlarging thrombosed aneurysm of the distal basilar artery. AB - The case of a 65-year-old man who had partial left third nerve palsy is reported. Radiographic examination disclosed a completely thrombosed giant suprasellar aneurysm. Although an angiogram appeared to indicate that his aneurysm arose from the distal basilar artery, he was also noted to have an unusual and ectatic distal internal carotid artery on the left side, and this was also felt to be a potential source of the aneurysm. Operative exploration was performed and confirmed the basilar artery as the sight of origin, and definitive therapy was deferred. The patient's progress was monitored, and for 3 years his neurological course was stable and there was no change in his radiographic abnormalities. During the 6 months following this period, the patient developed signs and symptoms of progressing hydrocephalus and was found to have significant enlargement of his still completely thrombosed giant aneurysm. This complicated case highlights the controversy regarding the management of this difficult condition, particularly with regard to endovascular therapies, and also provides insight into the evolution of this dynamic disease process. PMID- 2330096 TI - Chronic encapsulated intracerebral hematoma associated with cavernous angioma: a case report. AB - The case of a patient with a chronic encapsulated intracerebral hematoma associated with a cavernous angioma is reported. In spite of a huge space occupying lesion in the frontal lobe, our patient showed no focal neurological deficit. The clinical picture suggested a slowly growing brain tumor. Intraoperative findings revealed a liquefied intracerebral hematoma with a thick capsule. Pathological investigations demonstrated a capsule rich in neovascularity with a cavernous angioma attached to it. It is presumed that initial bleeding from the cavernous angioma encouraged capsule formation similar to the membrane of chronic subdural hematomas and that repeated bleeding from the capillaries of the capsule allowed the expansion of the hematoma. PMID- 2330098 TI - Treatment of intracranial epidermoid tumors. PMID- 2330097 TI - Primary closure of infected spinal wounds. AB - Although postoperative infections of spinal wounds are uncommon, when they occur, they cause considerable morbidity. The classic treatment for deep infected wounds of the spine involves opening the wound, packing it, and permitting secondary closure to occur through granulation. A combined total of 10 patients with infected postoperative spinal wounds (two cervical and eight lumbar) from the Lahey Clinic and the Cleveland Clinic were treated by primary closure. Infection was diagnosed, usually within 2 weeks of operation (average, 10.9 days), by increasing back pain, purulent drainage from the incision, cultures, and subfacial extension of the process. In one patient, an associated disk space infection was observed. Causative organisms were Staphylococcus aureus in five patients and Staphylococcus epidermidis in five patients. At the second operation, the wounds were opened and radically debrided, irrigated, and closed primarily over one or two large drains. Treatment with intravenously administered antibiotics was continued postoperatively; the duration of treatment varied from 10 days to 6 weeks, depending on the presence or absence of involvement of bone or disks. Complete resolution of the infections and primary healing of the wounds occurred in all patients. This technique offers advantages over the traditional technique of secondary wound closure by decreasing the amount of wound care and length of hospitalization and is recommended as the treatment of choice for patients with postoperative spinal wound infections. PMID- 2330099 TI - Somnambulism in adults. AB - We evaluated with clinical interviews and polysomnographic examinations 10 adults with the complaint of sleepwalking, often accompanied by violent behavior or self injury. During the polysomnographic studies, 8 patients had 47 distinct somnambulistic episodes. All episodes occurred in non-REM sleep, with 91% occurring in slow-wave sleep. Contrary to previous reports, episodes were not confined to the 1st 3rd of the night. Clinical EEGs were normal in 5 of 6 patients. In the 7 patients tried on 1 or more treatment regimens, clonazepam effectively suppressed the somnambulism in 5 of 6 patients in whom it was tried, carbamazepine in 1 of 3, flurazepam in 2 of 2, and a combination of clonazepam and phenytoin in one. PMID- 2330100 TI - Giant cell (temporal) arteritis: a treatable cause of multi-infarct dementia. AB - Dementia occurs infrequently in patients with giant cell (temporal) arteritis (GCA). Three elderly women with biopsy-proven GCA showed abrupt cognitive decline during periods of clinically active GCA, 1 to 6 months after diagnostic temporal artery biopsy, during periods of corticosteroid taper. One patient had additional clinical signs of cerebral infarction and other ischemic phenomena. Reinstitution of higher oral doses of corticosteroids successfully prevented further cognitive losses and permitted gradual but incomplete improvement of cognitive function in 1 patient. Neuropsychologic data from 2 patients 7 to 10 months after temporal artery biopsy suggested multifocal cognitive impairment, and the 3rd patient appeared clinically to be globally, severely demented. Neuroimaging studies revealed multiple areas of infarction, predominantly in the posterior circulation territory. One patient had bilateral vertebral artery occlusions (digital subtraction angiography) and bilaterally reduced carotid system perfusion pressures (oculoplethysmography). There were no associated cardiovascular risk factors or family history of dementia in these patients. PMID- 2330101 TI - Presenting the diagnosis of pseudoseizure. AB - Simultaneous video-EEG monitoring has allowed pseudoseizures to be effectively diagnosed. Discussing the results of the monitoring with the patient is the 1st step in treatment. We outline a protocol for presenting the diagnosis of pseudoseizure with the goal of conveying to the patient the importance of knowing the nonepileptic nature of the spells and the need for psychiatric follow-up. The protocol also allows elicitation of sexual abuse history and the use of suggestion to aid in controlling the pseudoseizures. PMID- 2330102 TI - Trigeminal sensory neuropathy associated with decreased oral sensation and impairment of the masseter inhibitory reflex. AB - We describe 4 patients with severe trigeminal sensory neuropathy whose main disability resulted from impaired intraoral sensation associated with disturbances of mastication and swallowing. Each patient had an abnormal blink reflex and jaw jerk. In addition, the masseter inhibitory reflex was absent in 3 patients and abnormal in the 4th. This reflex plays a role in the reflex control of mastication and can easily be elicited in normal subjects by stimulation of the skin and mucous membrane in the distribution of the 2nd and 3rd divisions of the trigeminal nerve while the jaw-closing muscles are contracting. Disturbed intraoral sensation combined with impaired trigeminal reflexes (particularly the masseter inhibitory reflex) interferes with neural mechanisms that regulate chewing and can be a source of severe disability in patients with trigeminal sensory neuropathy. PMID- 2330103 TI - An examination of male-female differences in progression and mortality of Parkinson's disease. AB - We conducted disability and mortality studies to determine if the male preponderance usually found in Parkinson's disease (PD) was reflected in different courses of the diseases in the 2 sexes. We analyzed longitudinal disability score in 47 men and 23 women with PD followed for 6 years at UCLA. We found no significant differences between the sexes in mean disability scores in any of the 6 years. Mean dopa dosage was significantly higher in men, possibly reflecting their generally larger body mass. Choreoathetosis, dementia, or other side effects did not differ between the 2 groups. We obtained observed to expected mortality ratios in 239 men and 132 women followed for 3,831 person years from records of 4 medical centers. Using the sex-specific US Life Tables to calculate expected mortality, we found the observed to expected ratio for the men was 1.7457 and for the women 2.4740, a significantly greater excess in female mortality. Analyses of mortality using tables which are not sex-specific will fail to uncover the decreased longevity in women with PD. We conclude that, despite the male preponderance in PD, men and women acquire it at the same age, have the same progression and duration of disease, and die at the same age; whereas, in the general population, women have a longer life expectancy than men. It is not known what factors protect women from incurring PD and what lowers their life expectancy to that of men when they do have the disease. PMID- 2330104 TI - 2-Amino-3-(methylamino)-propanoic acid (BMAA) in cycad flour: an unlikely cause of amyotrophic lateral sclerosis and parkinsonism-dementia of Guam. AB - We conducted an investigation of the levels of the neurotoxin 2-amino-3 (methylamino)-propanoic acid (BMAA) in cycad flour. Analysis of 30 flour samples processed from the endosperm of Cycas circinalis seeds collected on Guam indicated that more than 87% of the total BMAA content was removed during processing. Furthermore, in 1/2 the samples almost all (greater than 99%) of the total BMAA was removed. We found no significant regional differences in the BMAA content of flour prepared from cycad seeds collected from several villages on Guam. Testing of different samples prepared by the same Chamorro woman over 2 years suggests that the washing procedure probably varies in thoroughness from preparation to preparation but is routinely efficient in removing at least 85% of the total BMAA from all batches. Analysis of a flour sample that had undergone only 24 hours of soaking indicated that this single wash removed 90% of the total BMAA. We conclude that processed cycad flour as prepared by the Chamorros of Guam and Rota contains extremely low levels of BMAA, which are in the order of only 0.005% by weight (mean values for all samples). Thus, even when cycad flour is a dietary staple and eaten regularly, it seems unlikely that these low levels could cause the delayed and widespread neurofibrillary degeneration of nerve cells observed in amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam (ALS-PD). PMID- 2330105 TI - The relationship of age to outcome in myasthenia gravis. AB - This study, a retrospective review of 165 patients with myasthenia gravis, compares the course of the disease for patients with onset before 50 and at or after 50. There were no significant differences between age groups for presenting symptoms, but more of the older patients had progressed to severe disease. More of the younger than the older patients were in remission or were asymptomatic on medication at the last visit. Sixty-two percent of those treated with steroids developed complications, with a larger portion of these being in the older group. Cataracts, infection, and bone changes were particularly significant for the older population. Complications of azathioprine treatment and plasmapheresis were less common. Thymoma was more common in the older population; these patients did no worse than the population as a whole. Sixty-five percent of our patients have undergone thymectomy, most by a modified transsternal approach. A much larger portion of those who underwent thymectomy were in remission at the last visit than those who did not. PMID- 2330106 TI - The characteristics and mechanisms of visual disturbance associated with anticonvulsant therapy. AB - Eight epileptic patients receiving anticonvulsants had recurrent visual disturbances in the form of diplopia and oscillopsia in the horizontal or vertical planes. The symptoms could be ascribed to impaired vergence mechanisms, vertical nystagmus, or abnormalities of the vestibulo-ocular reflex. Other eye movements, such as pursuit and gaze-holding, were also affected, but did not lead to complaints. Episodes of visual disturbance were often preceded by prodromes of ocular or systemic discomfort, after which oscillopsia or diplopia evolve rapidly. The symptomatology was stereotyped but unique for each patient and may reflect idiosyncratic susceptibility to the ocular motor side effects of anticonvulsants. Six of the 8 patients were taking carbamazepine and phenytoin in combination, which have similar effects on the ocular motor system. PMID- 2330107 TI - Pathology of temporal lobe foci: correlation with CT, MRI, and PET. AB - Twenty-six patients with medically refractory complex partial seizures had temporal lobectomy after evaluation, which included prolonged scalp EEG recordings, positron emission tomography (PET), MRI, and x-ray CT. PET showed a region of focal interictal temporal hypometabolism corresponding to electrographic localization of seizure onset in 21. Five patients had a region of increased MRI signal intensity on the spin echo image in the region of the EEG focus, 2 had an abnormality ipsilateral to but distinct from the EEG focus, and 1 had bilateral findings. CT was abnormal in 3 cases; 2 had tumors. Three patients had low grade tumors (1 with a normal PET). PET can detect metabolic dysfunction associated with mild pathologic changes in epileptic foci, but increased signal intensity on MRI does not necessarily correlate with the degree of pathologic abnormality. Tumors may be less likely when both CT and MRI are normal. PMID- 2330108 TI - Pupillary responses to dilute pilocarpine in preganglionic 3rd nerve disorders. AB - Supersensitivity of the iris sphincter to dilute parasympathomimetic agents is considered a diagnostic hallmark of a postganglionic oculomotor nerve disorder. Nine of 13 patients with preganglionic 3rd nerve palsies showed supersensitive pupillary responses using pilocarpine 0.1%. The presence of supersensitivity was not related to the cause of 3rd nerve dysfunction or interval time from onset to testing, but was related to the extent of associated iris sphincter paresis. Some patients with long-standing preganglionic 3rd nerve palsies had features of postganglionic damage, including light-near dissociation and segmental paresis of the iris sphincter. These observations suggest that 1 mechanism of cholinergic supersensitivity in some chronic cases of preganglionic 3rd nerve disorders may be transsynaptic degeneration of postganglionic fibers. In another set of experiments, pharmacologically dilated pupils in normal subjects constricted more to dilute pilocarpine than their normal-sized fellow pupils. Cholinergic supersensitivity in pupil-involving 3rd nerve palsies might also occur simply because the affected pupil is larger than the unaffected pupil. PMID- 2330109 TI - Intrathecal synthesis of anti-HIV IgG: correlation with increasing duration of HIV-1 infection. AB - We determined intrathecal synthesis (ITS) of anti-HIV-1 immunoglobulin in 62 CSF samples from 51 HIV-1 seropositive homosexual men using an ELISA technique with paired serum and CSF samples diluted to a concentration of IgG of 10 micrograms/ml. All subjects were neurologically normal and none was taking zidovudine. We estimated duration of HIV-1 infection from semiannual serologic testing during the 3-year period before CSF analysis and detected ITS of anti-HIV 1 immunoglobulin in 2 of 12 (17%) of those with less than 18 months of HIV-1 seropositivity, in 3 of 21 (14%) with 19 to 36 months, and in 13 of 29 (45%) with greater than 36 months of HIV-1 seropositivity (p = 0.037). There was a trend toward an inverse relationship between level of ITS and the peripheral blood T helper lymphocyte count. This study demonstrates that increasing ITS of anti-HIV 1 IgG is related to duration of HIV-1 infection and suggests an inverse correlation with systemic immune status. The detection of ITS of anti-HIV-1 immunoglobulin is not necessarily a marker of clinically overt neurologic involvement. PMID- 2330110 TI - Prognostic implications of hyperglycemia and reduced cerebral blood flow in childhood near-drowning. AB - We retrospectively examined the clinical courses of 20 children with severe near drowning and divided their outcomes into 3 groups: normal (4), persistent vegetative state (9), and dead (7). We reviewed serial blood glucose levels and cerebral blood flow measured by stable xenon computed tomography within the 1st 48 hours of admission to determine whether they were predictive of outcome. Total, frontal gray, frontal white, and temporal and parietal gray matter cerebral blood flows were significantly decreased in children who died compared with those who completely recovered. Only 1/2 the children surviving in a vegetative state had decreased flows compared with those who recovered. An elevated initial blood glucose was highly predictive of those patients who died (mean, 511 +/- 110 mg%) or those with vegetative survival (465 +/- 104 mg%) compared with those who recovered completely (238 +/- 170 mg%). The predictive value of initial blood glucose alone (68%) or CBF alone (50%) was similar to that of clinical rating scales or immersion/resuscitation times. The combination of blood glucose with CBF improved predictability to 79%. Our results suggest that CBF measurements are predictive of eventual death but cannot differentiate normal from vegetative survival. Combining multiple laboratory studies may be of value in predetermining the eventual outcome in near-drowning. PMID- 2330111 TI - H-reflex recovery curve and reciprocal inhibition of H-reflex in different kinds of dystonia. AB - We studied the H-reflex recovery curve and reciprocal inhibition of the H-reflex bilaterally in the upper limb of 5 patients with generalized dystonia, 5 patients with blepharospasm, 10 patients with spasmodic torticollis, and 14 patients with writer's cramp. We compared the results with those obtained from a group of healthy volunteers. The recovery curve of the H-reflex was normal in patients with writer's cramp or blepharospasm, but showed an increase of the physiologic recovery at a 200 msec delay in patients with spasmodic torticollis or generalized dystonia. Reciprocal inhibition of the H-reflex showed a decrease in the amount of inhibition in all the patient groups and a facilitation of the H reflex during the 3rd period of inhibition in the patients with spasmodic torticollis or generalized dystonia. PMID- 2330113 TI - Cerebellar venous infarction: case report with clinicopathologic correlation. AB - A diabetic man developed a severe hyperosmolar state resulting in coma. CT of the head showed bilateral cerebellar hemorrhages. Despite medical treatment, he deteriorated and died. At autopsy, the straight sinus was thrombosed. There were bilateral, hemorrhagic, cerebellar venous infarctions. This condition is rare because of abundant collateral venous drainage. PMID- 2330112 TI - Risk of cardiac surgery in patients with prior stroke. AB - We retrospectively examined the clinical outcome in 126 patients with a history of ischemic stroke undergoing open heart surgery (OHS). We classified prior strokes as recent or remote and by degree of neurologic deficit. Seventeen patients (13.4%) had new strokes or worsening of prior deficits, but only 4 were moderate-severe in degree (3.2%). There was no significant difference in new stroke rates between recent and remote stroke groups. New strokes more frequently involved worsening of prior deficits in the recent stroke group, while strokes in different areas of the brain occurred more often in the remote stroke group. Extracranial occlusive disease was not a factor. Intraoperative hypotension was more frequent in the recent stroke group, suggesting persistent hemodynamic vulnerability. PMID- 2330114 TI - Genealogical reconstruction of myotonic dystrophy in the Saguenay-Lac-Saint-Jean area (Quebec, Canada). AB - The prevalence of myotonic dystrophy (MyD) in the Saguenay-Lac-Saint-Jean (SLSJ) region (Quebec, Canada) is 30 to 60 times the world's prevalence. We identified 746 patients (673 still alive) distributed in 88 families. Using a population based register of the SLSJ area and several marriage repositories from northeastern Quebec, we could trace back all patients to a couple who settled in "Nouvelle-France" in 1657. The MyD gene was then passed on over 10 to 14 generations. This genealogical reconstruction is a strong argument in favor of the genetic homogeneity of MyD in the SLSJ region. PMID- 2330115 TI - Lower motor neuron disease in a patient with autoantibodies against Gal(beta 1 3)GalNAc in gangliosides GM1 and GD1b: improvement following immunotherapy. AB - We followed a patient with a lower motor neuron form of motor neuron disease whose neurologic disorder improved following immunotherapy. The patient did not have an M protein but did have IgM antibodies to ganglioside GM1 detectable at serum titers of 1:2,000 by ELISA. These antibodies were found only in the IgM fraction with lambda light chains and immunoreacted with GD1b and Gal (beta 1-3) GalNAc. PMID- 2330116 TI - Decreased efficacy of levodopa with carbidopa in parkinsonian patients after adrenal-to-caudate implants. AB - We studied 6 parkinsonian patients 6 weeks after unilateral adrenal-to-caudate implants. We withheld medications the night before each of 2 study days and gave the patients a single test dose of either a combination of levodopa and carbidopa, or levodopa alone in double-blind random order. We administered the modified Columbia scale, objective measurements of rigidity and movement velocity, and the pegboard test at regular intervals after the single test dose. The results revealed that the improvements in performance recorded by the Columbia scale and the pegboard test were significantly less on the side contralateral to the operation when patients received carbidopa, whereas there was no significant difference in performance between the 2 observations on the ipsilateral side. Carbidopa apparently crossed the disrupted blood-brain barrier and lowered the efficacy of levodopa. PMID- 2330118 TI - Terminal component of complement (C9) in the cerebrospinal fluid of patients with multiple sclerosis and neurologic controls. AB - We measured the concentration of C9 in the CSF and plasma of 93 consecutive patients referred for CSF examination in an outpatient multispecialty clinic. We noted no differences in CSF C9 or C9 index between patients with multiple sclerosis and neurologic controls. PMID- 2330117 TI - Loss of facial sweating and flushing in Holmes-Adie syndrome. AB - We investigated pupillary responses to parasympathetic (pilocarpine) and sympathetic agents (tyramine, cocaine, and phenylephrine) in a 51-year-old woman with tonic pupils, loss of muscle stretch reflexes in the limbs, and hemifacial loss of sweating and flushing (Ross' syndrome). A smaller pupillary response to tyramine and cocaine eyedrops on the symptomatic side indicated that outflow was disrupted in the postganglionic section of the ocular sympathetic pathway. A greater response to phenylephrine eyedrops on this side was consistent with denervation supersensitivity to adrenergic agents. Loss of thermoregulatory sweating and flushing and emotional blushing in the forehead, cheek, and chin indicated that sympathetic disruption was proximal to the bifurcation of the common carotid artery, probably in the superior cervical ganglion. A similar degenerative process may be responsible for loss of muscle stretch reflexes, tonic pupils, and other autonomic disturbances in Ross' syndrome. PMID- 2330119 TI - Complex partial status epilepticus in a patient with leptomeningeal carcinomatosis. PMID- 2330120 TI - Status epilepticus secondary to breath-holding and pallid syncopal spells. PMID- 2330122 TI - Depth versus subdural electrodes. PMID- 2330121 TI - Adrenal-to-caudate transplantation. PMID- 2330123 TI - Imaging of spinal metastases. PMID- 2330124 TI - Traumatic basal ganglia hemorrhage. PMID- 2330125 TI - Cocaine withdrawal dystonia. PMID- 2330126 TI - Ibuprofen meningitis. PMID- 2330127 TI - Sternocleidomastoid innervation. PMID- 2330128 TI - Possible role of zinc in the selective degeneration of dentate hilar neurons after cerebral ischemia in the adult rat. AB - The fluorescent dye 6-methoxy-8-p-toluene sulfonamide quinoline (TSQ) was used to monitor the distribution of zinc in the hippocampus and fascia dentata of adult rats subjected to 20 min of cerebral ischemia. In normal brains TSQ stains only neuropil, in particular the mossy fiber layers in the dentate hilus (CA4) and CA3, but within 2 h after ischemia, TSQ-fluorescent cells were observed in the dentate hilus. At longer survival times TSQ-positive cells stained positively with acid fuchsin, a sign of cellular degeneration. At the same time a decrease in the TSQ fluorescence of the mossy fiber terminals in the dentate hilus (CA4) and the CA3 mossy fiber layer was noted. The observations suggest that zinc many play a role in the selective death of dentate hilar neurons after cerebral ischemia. PMID- 2330129 TI - Molluscan insulin-related neuropeptide promotes neurite outgrowth in dissociated neuronal cell cultures. AB - The formation of neurites in isolated neurones of the snail Lymnaea stagnalis in primary culture was studied. The insulin-related neuropeptide (MIP: Molluscan insulin-related peptide) produced by the neuroendocrine light green cells (LGCs) of Lymnaea stimulated neurite formation, both in isolated unidentified central neurons and in the LGCs. The effect of MIP was dose dependent. It was significant from the second day of culture and amounted up to an 8-fold increase in neurite outgrowth after 3 days. The results add a functional aspect to the evolutionary relationship of MIP with mammalian insulin and insulin-related peptides and suggest that the LGCs, which stimulate growth, are also involved in development of the nervous system. PMID- 2330130 TI - Lesion patterns of vasoactive intestinal polypeptide-containing neurons in the myenteric plexus induced by clamping or transsection of rat jejunum. AB - The acute reactions of vasoactive intestinal polypeptide (VIP)-containing neurons in the myenteric plexus of the rat jejunum in response to circumferential clamping or transection/reanastomosis were evaluated in a detailed time course of up to ten days. Whereas in sham-operated controls VIP immunostaining was confined exclusively to varicose fibers, either clamping or transection induced the appearance of strongly VIP-immunoreactive beaded neuronal processes and neuronal perikarya in the oral part of the lesion one day postoperatively. After five days strongly immunostained varicose fibers orientated in the longitudinal axis of the gut towards the lesion reappeared suggestive of the onset of regenerative processes. PMID- 2330131 TI - Recognition of egocentric and allocentric visual and auditory space by neurons in the hippocampus of monkeys. AB - Neuronal activity in the hippocampus was recorded in the awake monkey during presentation of visual and auditory stimuli from various directions. About 10% of the neurons coded visual and/or auditory information from unique directions. Some of these neurons were stimulus-selective, and others were not. Three types of neurons were identified by rotating the animals: egocentric and allocentric, and indeterminate. The results are consistent with a role of the hippocampus in spatial memory. PMID- 2330132 TI - Ethylcholine aziridinium ion depletes acetylcholine and causes muscarinic receptor supersensitivity in rat retina. AB - Three weeks after a single intravitreal injection of ethylcholine aziridinium ion (AF64A), there was a significant depletion of retinal acetylcholine (ACh) content. The depletion was accompanied by an increase of [3H]quinuclidinyl benzilate binding sites and a greater than control conversion of myo-[3H]inositol to inositol monophosphate following incubation with ACh. These changes are consistent with receptor supersensitivity due to AF64A-induced denervation. PMID- 2330133 TI - Chronic administration of amphetamine increases glutamic acid decarboxylase activity in the rat substantia nigra. AB - The glutamate decarboxylase activity in the rat cerebellum, frontal cerebral cortex, hypothalamus, substantia nigra and nucleus caudatus, was measured after either acute or chronic administration of (+)-amphetamine (1.35 and 5.4 mg/kg, i.p.). It was found that following 45 days of treatment the highest dose of the drug induced a selective increase of glutamate decarboxylase activity in the substantia nigra. Also in addition to the known changes in body weight, behavior and food-intake, some of the rats (5 out of 80 rats) treated with the highest dose of (+)-amphetamine developed a self-mutilating behavior. These results suggest that after the repeated administration of a high dose of (+)-amphetamine the activity of the striatonigral GABAergic pathway is increased and supports the idea that gamma-aminobutyric acid output neurons might convey dopamine-related functions. PMID- 2330134 TI - Changes in pontine muscarinic receptor binding during sleep-waking states in the rat. AB - Number and affinity of pontine muscarinic receptors were examined in rats sacrificed during polygraphically defined wakefulness (W), synchronized sleep (S) and desynchronized sleep (D). Saturation binding assays with (-) [3H]quinuclidinyl benzilate [( 3H]QNB) showed that muscarinic receptor levels were higher in W and D than in S. These findings indicate that brain receptor levels may change in relation to sleep-waking states. The significance of such changes in relation to the time course of sleep-waking states, as well as the possibility that the number of pontine muscarinic receptors plays a role in the triggering of D are discussed. PMID- 2330135 TI - Sera from MS patients and normal controls opsonize myelin. AB - Fc receptor-dependent myelin phagocytosis has been proposed as a mechanism of demyelination in multiple sclerosis (MS). The object of this study was to determine whether MS patients' sera are more opsonic for myelin than normal controls' sera. Opsonization was tested by culturing thioglycollate elicited murine peritoneal macrophages with 125I-labelled, serum-sensitized bovine central myelin. The two groups of sera were found to opsonize myelin equally well after 30 and 120 min incubations. We conclude that MS patients' sera are not more opsonic for myelin than sera from normal controls. PMID- 2330136 TI - Thinkers and doers. PMID- 2330137 TI - Another response to Knapke. PMID- 2330138 TI - Nursing education appropriations. PMID- 2330139 TI - Development management for nursing administration. AB - What are the needs of a nurse administrator in a developing country? For that matter, what are the requirements for a nurse administrator in areas of lesser developed delivery in this country (e.g., care of the homeless, care of indigent populations)? Heyden, Luyas, and Henry look at the educational needs of these nurse managers and compare the needs to the typical education received in nursing administration programs. PMID- 2330140 TI - Knowledge and skills for nurse administrators. AB - How should nurse administrators be educated for practice in today's complex environment? Mark, Turner, and Englebardt provide a thoughtful perspective on that question. The authors analyze the educational needs of two levels: the nurse executive and the nurse manager, and they look at all aspects of an effective graduate program for both career choices. PMID- 2330141 TI - Nursing administration research as a paradigm reflection. AB - Nursing administration research: What has been done? What needs to be done? McDaniel analyzes the research completed in recent years, describing the extant research as atomistic, focused on the nurse provider, not on the organization, administration, or patient. She suggests directions for future nursing administration research: multisite and multivariate analyses of the complex and dynamic nature of health systems, including international perspectives. PMID- 2330142 TI - Technology and structure of nursing organizations. AB - Theory building and theory application in nursing administration enable the nurse executive to work more effectively at the managerial task. Alexander and Mark apply a model that allows for comparison and contrast between various nursing units based on the nature of their work as assessed on the variables of technology and structure. In this model, technology is assessed on three dimensions: instability, variability, and uncertainty; and structure is assessed as to vertical participation, horizontal participation, and formalization. Cases studies clarify the model and show its application. PMID- 2330143 TI - Symposium on nutrition. Children who won't eat. PMID- 2330144 TI - Symposium on nutrition. Are you getting enough? PMID- 2330145 TI - How to deal with data. PMID- 2330146 TI - Health education. Advice given to coronary patients. PMID- 2330147 TI - Quality awareness. PMID- 2330148 TI - The best of Bradford. PMID- 2330149 TI - Farewell then, dippy egg... PMID- 2330150 TI - One day at a time. PMID- 2330151 TI - Researching the options. PMID- 2330153 TI - Symposium on nutrition. Diet in pregnancy. PMID- 2330152 TI - Nurse management and politics. PMID- 2330154 TI - Symposium on burns. Friction burns. PMID- 2330155 TI - Symposium on burns. Psychological effects. PMID- 2330156 TI - Nurses' use of first names. PMID- 2330157 TI - One day at a time. PMID- 2330158 TI - Benign and malignant skin conditions. PMID- 2330159 TI - Sheffield: pioneers with a purpose. PMID- 2330160 TI - Community nursing. The age of the practice nurse. PMID- 2330161 TI - What security do we offer patients? PMID- 2330163 TI - Road crash experiences during the fourteenth and fifteenth years of life: an overview. AB - From a sample of 848 teenagers, 113 individuals had experienced 121 road traffic crashes. Five of the incidents involved a pedestrian, 62 a bicyclist, six a motor cyclist, 47 a motor vehicle passenger and one a motor vehicle driver. Sixty-two percent of the crashes involved injury and 67% vehicle immobilisation. Five of the injured teenagers were admitted to hospital but the majority (55%) were treated at a hospital accident and emergency department and then discharged. The official reporting of the crashes to the Ministry of Transport was examined and the problems of underreporting and biases in reporting are discussed. PMID- 2330162 TI - Tutors move to quieten student fear of Project 2000. PMID- 2330164 TI - Health research in New Zealand--prospects and problems. PMID- 2330165 TI - The rehabilitation of injured workers in New Zealand: a pilot study. AB - At the request of the local office of the Accident Compensation Corporation (ACC) we established a centre which offered a multidisciplinary rehabilitation programme consisting of a full assessment and an eight week individually planned and monitored fitness programme. The clients progressed to occupational therapy, work trials, and later to paid work. The programme included education about back care and health maintenance, and relaxation techniques. Of the 48 injured people who attended the centre, 37 were assessed as suitable to enter the programme, and 32 people took part. Outcome, measured as return to work or change in assessed fitness to work, was not related to age, sex, marital status, length of time since accident, or work category. Only 25% of workers returned to jobs in medium or heavy manual work. Sickness impact profile total and physical scores improved over the programme, but did not correlate significantly with return to work or fitness for work. Client perception of benefit was not significantly related to outcome. We analysed data from the 20 clients with claims longer than 6 months separately because matched case controls could not be provided by the ACC. Six months after completion of the programme, four were in paid employment, four in prolonged work trials, one in a job partly paid by the ACC, and one setting up his own business. Their return to the work force demonstrated the effectiveness of the centre in restoring people to function after prolonged periods of inactivity. PMID- 2330166 TI - An assessment of a postgraduate examination of competence in general practice: Part 1--Reliability. AB - The 1987 part one examination of the Royal New Zealand College of General Practitioners was subjected to an evaluation. The format of the examination and the scope of the review is described. This paper describes the assessment of the reliability of components of the examination. Simulations showed acceptable reliability, however the reliability of the written paper was less satisfactory. The ways in which such reliability may be enhanced are described. PMID- 2330167 TI - Evaluation of a new fine needle technique in routine percutaneous liver biopsy. AB - A new fine needle aspiration biopsy technique (Vacu-Cut, 19.5 G) was compared to the 17 G Menghini needle in 20 consecutive patients scheduled for routine percutaneous liver biopsy (10 at random with each needle). The Menghini system was superior in producing sufficient material for histological assessment with 90% success on first pass biopsy (100% with 12 passes in 11 patients) as compared to 60% with the Vacu-Cut needle (90% with 16 passes in 10 patients). The latter was easier to use. Ability to reach a histological diagnosis was 100% with both needles. No major complications occurred: only one Vacu-Cut patient (10%) developed pain at the puncture site as compared to seven patients (65%) in the Menghini group, irrespective of number of passes. The ease of use and lower incidence of pain may favour the Vacu-Cut needle in selected ill patients. PMID- 2330168 TI - Immature respiratory control. PMID- 2330170 TI - For the price of a pen! PMID- 2330169 TI - Chlamydial antibodies. PMID- 2330171 TI - Rest home subsidies for psychiatric and psychopaedic patients. PMID- 2330172 TI - Medical research, who minds the minders. PMID- 2330173 TI - Mammography and breast cancer. PMID- 2330174 TI - Medical Practitioners Disciplinary Committee: professional misconduct findings against Dr D W Steeper. PMID- 2330175 TI - Medical Practitioners Disciplinary Committee: Inadequate post delivery care: Dr S H Raymond. PMID- 2330177 TI - Confidence is needed to disagree. PMID- 2330176 TI - Learning to learn. PMID- 2330178 TI - The "nurses do everything" dilemma. PMID- 2330179 TI - A nursing integration framework based on standards of practice. PMID- 2330180 TI - The 10 stages of change. PMID- 2330181 TI - Lobbying: the hows and wherefores. PMID- 2330182 TI - Cost of non-nursing tasks. PMID- 2330183 TI - Stress management in nursing. PMID- 2330184 TI - Combining chart audits and telephone interviews. PMID- 2330185 TI - Job satisfaction: impact of counseling and evaluation. PMID- 2330186 TI - Prepaid dental law in New York. PMID- 2330187 TI - Needle sticks & AIDS. PMID- 2330188 TI - Limbal wedge resection at the time of intraocular lens surgery for reducing postkeratoplasty astigmatism. AB - Thirteen limbal wedge resections performed to reduce postkeratoplasty astigmatism in patients undergoing secondary intraocular lens placement were reviewed. Eleven of the 13 procedures reduced preoperative astigmatism 3.12 diopters (+/- 1.77 D; range, 0.50 D to 6.25 D). The average follow-up time was 17 months (range, 4 to 36 months). The average flat/steep ratio was 1.19 (+/- 0.96), indicating approximately equal degrees of corneal flattening and steepening. Average central corneal keratometric values steepened 0.47 D, with a range of 0.56 D of flattening to 2.41 D of steepening. Keratometric values were stable by 4 months in most patients. All patients except one with amblyopia had a corrected visual acuity of 20/60 or better. A dellen formation developed in one case, but it caused no permanent negative visual complications. As generally found in previous studies, each 0.1-mm wedge-width resected induced 1 D of astigmatic correction. Limbal wedge resection in conjunction with intraocular lens implantation can safely and effectively reduce astigmatism following penetrating keratoplasty. PMID- 2330189 TI - Temporary conduction block of optic nerve after retrobulbar anesthesia. AB - Three patients who experienced temporary visual loss after retrobulbar anesthesia with 2% lidocaine (Xylocaine) are described. Visual evoked potentials (VEPs) consistently increased in latency and decreased in amplitude. Abnormal VEPs such as these recorded for humans after retrobulbar anesthesia are, to our knowledge, reported here for the first time. PMID- 2330190 TI - Neovascular glaucoma following pars plana vitrectomy for complications of diabetic retinopathy. AB - The patient charts of 81 consecutive vitrectomies performed for complications of proliferative diabetic retinopathy were reviewed. Sixty-five preoperative, intraoperative, and postoperative variables were analyzed. In eyes with completed panretinal photocoagulation, only postoperative retinal detachment had a statistically significant correlation with postvitrectomy development of neovascular glaucoma. Eighty-three percent of eyes with detached retinas, as compared with 4% of eyes with attached retinas, developed neovascular glaucoma (P less than .00001). Aphakia alone did not have a statistically significant effect on the development of neovascular glaucoma; however in the presence of retinal detachment the incidence was very high (92%). Our study shows that a completely attached retina and aggressive panretinal photocoagulation are of paramount importance in decreasing the risk of neovascular glaucoma following vitrectomy for complications of proliferative diabetic retinopathy. PMID- 2330191 TI - Outpatient and abbreviated hospitalization for vitreoretinal surgery. AB - We retrospectively reviewed 255 consecutive scleral buckling and vitrectomy operations dividing the patients into two groups. One group was managed traditionally with general anesthesia and postoperative hospitalization. The second group was managed with local anesthesia and with no hospitalization or abbreviated hospitalization whenever possible. There was no difference in the technical or functional success rates achieved in the two groups. We conclude that vitreoretinal surgery may be performed safely and effectively on an outpatient basis in selected cases. PMID- 2330192 TI - A multipurpose dye laser photocoagulation system. AB - We modified a single argon/dye laser photocoagulator by adding two optical fibers so that it could be used with a slit-lamp microscope, an operating microscope, and with an endophotocoagulation probe. One fiber is attached to a nearby slit lamp microscope; the other extends approximately 70 m and can be connected to either an operating microscope or an endophotocoagulation probe. An electrically operated mirror inside the machine controls which of the two fibers the laser beam passes through. Separate control boxes for each fiber permit direct regulation of the photocoagulation process in all situations. PMID- 2330193 TI - Accommodative intraocular lens with spring action. Part 1. Design and placement in an excised animal eye. AB - We designed an intraocular lens (IOL) with spring action, which we call the Spring IOL, with the idea of providing a slight but adequate accommodative power. The Spring IOL consists of two 6.0-mm optics, held 4.38 mm apart, and four flexible loops. The optics are made of polymethylmethacrylate (PMMA) and the loops of polyvinylidene fluoride. The lens's refractive power is provided by the anterior optic; the posterior optic acts as a footplate to restrict the anteroposterior movement of the anterior optic. By torsionally compressing the obliquely arranged loops, a 10.0-mm 3-dimensional IOL can be reduced to 6.0 mm and inserted in the capsular bag through a 3.5-mm capsular opening. Because the Spring IOL is made of the same materials as conventional IOLs, most of the problems hindering the development of a refilling material (which could also provide accommodation) are avoided. In this first report we discuss the design of the lens, the refractive theory involved, and our experience inserting it in an excised animal eye. PMID- 2330194 TI - A simplified method of monocanalicular silicone intubation. AB - We present a simplified method of monocanalicular silicone intubation for the repair of single canaliculus lacerations. A monocanalicular loop of tubing running from the punctum, through the lacerated canaliculus, and out the cutdown site over the lacrimal sac, provides a secure silicone tube stent. PMID- 2330195 TI - A 61-year-old man with a painless red eye and decreased visual acuity. PMID- 2330196 TI - Avoiding complications of orbital surgery: the orbital branches of the infraorbital artery. AB - Adequate exposure in surgery along the orbital floor requires recognition and often division of the orbital branches of the infraorbital artery. Failure to recognize this orbital vascular bundle may lead to severe complications, including visual loss. PMID- 2330197 TI - Monitoring anterior chamber depth following filtration surgery. PMID- 2330198 TI - Difficulties of proper ophthalmic care in developing countries. PMID- 2330199 TI - Accessory lacrimal glands. PMID- 2330200 TI - Peribulbar vs. retrobulbar anesthetic techniques. PMID- 2330201 TI - Good medical care is rationed. PMID- 2330202 TI - Blindness following blepharoplasty: two case reports, and a discussion of management. AB - We present two cases of unilateral permanent visual loss following four-eyelid blepharoplasty. Clinical and radiographic evidence suggested orbital hemorrhage was the cause of visual loss in both cases. In particular, electrophysiologic tests indicated that optic nerve dysfunction, and not retinal ischemia, was responsible for loss of vision. Timely orbital decompression is the cornerstone of managing these dramatic cases. PMID- 2330203 TI - The success rate of silicone intubation in congenital lacrimal obstruction. AB - In our series of 100 patients who had unsuccessful probing for congenital nasolacrimal duct obstruction, all had silicone intubation associated with infracturing of the inferior turbinate. The age range was from 7 months to 4 years at the time of intubation. Sixty patients had tubes in for 1 year, and all but one, a 3-year-old girl, were treated successfully. Of the 40 who had tubes in place for less than 1 year, 38 were treated successfully. The two unsuccessful cases were those of a 3-year-old boy and a 4-year-old boy, whose tubes were removed at 3 and 4 months, respectively. The overall success rate in our series was 97%; all patients younger than two years old at the time of intubation were treated successfully. PMID- 2330204 TI - Muller's muscle-conjunctival resection procedure in the treatment of ptosis in Horner's syndrome. AB - The predictability of the phenylephrine test and the efficacy of the Muller's muscle-conjunctival resection procedure in the management of blepharoptosis in six cases of Horner's syndrome were assessed. Before phenylephrine testing or surgery, an average of 2.3 mm of ptosis was present. Topical phenylephrine elevated upper lids an average of 2.2 mm. The amount of elevation produced by the phenylephrine guided the amount of Muller's muscle and conjunctiva resected. Postoperative upper lid levels were exactly symmetrical in five of six patients. In one patient the previously ptotic lid was 0.5 mm higher than the contralateral lid. Even though Muller's muscle is rendered nonfunctional in Horner's syndrome by denervation, the Muller's muscle-conjunctival resection procedure proved to be a very effective method of treating ptosis in this setting. Our findings imply that the mechanism by which this procedure alleviates ptosis is independent of active contraction of Muller's muscle. PMID- 2330206 TI - Frontiers of vision. 10th anniversary conference of the British College of Optometrists. 23-25 April 1990, London. PMID- 2330205 TI - Lacrimal gland prolapse in craniosynostosis syndromes and poor function congenital ptosis. AB - Lacrimal gland prolapse is an important, though uncommon, feature found in craniofacial abnormalities as well as in cases of poor function congenital ptosis. It occurs secondary to a number of conditions, including increased posterior pressure secondary to decreased orbital volume; also, supportive structures of the gland often may be weak in conjunction with a poor function ptosis or as a result of trauma at the time of major reconstruction. Recognition of the prolapsed gland and its replacement into the lacrimal gland fossa in craniosynostosis syndromes, as well as in cases of poor function congenital ptosis in general, allows the temporal eyelid to approach a more normal position, yielding an improved functional and cosmetic result. PMID- 2330207 TI - Investigation of progressive addition lens patient tolerance to dispensing anomalies. AB - Numerous reasons have been cited for patient non-tolerance to Progressive Addition Lenses (PALs). This paper considers two presbyopic subject populations - those who successfully wore PALs (n = 20), and those who were non-tolerant to them (n = 18). The dispensing accuracy of the PALs worn by subjects was assessed and the surface quality of those lenses worn by unsuccessful patients studied. These factors do not account for any significant differences between the two groups, suggesting that other causes must separate the subject populations. PMID- 2330208 TI - The reliability of the Pelli-Robson contrast sensitivity chart. AB - Normative contrast sensitivity (CS) data were obtained using the commercially available Pelli-Robson chart from the dominant eye of 30 young (mean (+/- SD) age 22.5 +/- 4.3 years) and 42 older (mean (+/- SD) age 70.2+/- 6.7 years) subjects with normal healthy eyes. The majority of young subjects were found to have a CS of 1.80 log units or above. The majority of the older subjects were found to have a CS of 1.65 log units or above. CS results were obtained using both sides (A and B) of the Pelli-Robson chart from 30 (15 young and 15 older) of these subjects. These measurements were repeated under identical conditions, 2 weeks later. There was no significant difference between the results from sides A and B of the chart. The CS scores were shown to be repeatable to within +/- 0.15 log units or +/- 1 step. Therefore a significant change in CS score is +/- 2 steps or 0.30 log units. Slight improvements in reliability could be obtained by more careful permutation of letters on each step and a smaller step size. The restriction against these changes is the ensuing increased chart size. PMID- 2330209 TI - Horizontal fusional amplitudes after adaptation to prism. AB - Horizontal fusional limits and lateral phorias were measured subjectively on five normal subjects after adaptation to increments of base-in and base-out prism. Both the phoria and the fusional limits were found to change by approximately the amount of the adapting prism. The fusional amplitudes (the difference between the phoria and the fusional limits) were relatively unaffected by vergence adaptation except at the largest values of adapting prism. These results are in agreement with current models of disparity vergence eye movement control which suggest that there are independent fast and slow fusional vergence mechanisms, each with its own saturation limit. PMID- 2330210 TI - Heterophoria and monocular occlusion. AB - Prism adaptation responses in orthophoric, exophoric and esophoric subjects are compared and found to be significantly different. Following a prolonged period of monocular occlusion the prism adaptation responses were compared, after occlusion the differences are no longer significant. This supports the theory that vergence (prism) adaptation is responsible for the existence of heterophoria. This paper shows that changes in heterophoria with monocular occlusion are caused by desaturation of prism adaptation. PMID- 2330211 TI - The effect of monocular defocus on binocular contrast sensitivity. AB - The monocular contrast sensitivity loss with defocus is well known. We measured binocular contrast sensitivity of sinewave gratings of 6 c/deg in the presence of different levels of monocular defocus. In the absence of defocus, the binocular sensitivity was about 42% higher than monocular. With increasing monocular defocus, the binocular sensitivity decreased steadily until it reached a level below the monocular, showing binocular inhibition. The clinical implications of binocular inhibition with monocular defocus are discussed. PMID- 2330212 TI - Binocular contrast sensitivity with monocular glare disability. AB - Glare disability plays an important part in the investigation and assessment of cataract. We investigated the effect of monocular glare disability on binocular contrast sensitivity. The magnitude of binocular summation was measured at different degrees of monocular glare disability. In the absence of glare, maximum binocular summation was shown. With increasing glare disability, the degree of binocular summation decreased steadily until binocular inhibition was produced. Binocular inhibition is defined as a reduction in binocular sensitivity to reach a level below the monocular. The clinical implications of binocular inhibition with monocular glare disability are discussed. PMID- 2330213 TI - Comparison of the standard and Adams desaturated D-15 tests with congenital colour vision deficiencies. AB - The Adams desaturated D-15 was designed to be administered to patients with acquired colour vision defects by simply reducing the chroma of the Munsell colours by 2 for each cap in the test. In this study, the performance of the Adams desat D-15 in the assessment of congenital colour vision deficiencies is evaluated. The standard D-15 and Adams desat D-15 tests were administered to 75 congenital red-green colour deficient subjects who had been diagnosed on the basis of their performance on the Nagel anomaloscope Mark 1. The results were analysed in terms of the directions, extent and specificity of errors and compared with the diagnosis on the Nagel anomaloscope. Of the 13 colour-deficient subjects who made no errors on the standard D-15, 1 failed the Adams desat D-15 and 2 made single crossings. No colour-deficient subject who failed the standard D-15 made anything less than a simple inversion of adjacent caps on the Adams desat D-15. The Adams desat D-15 did not perform as well as the standard D-15 in identification of the type of defect in dichromats. On the basis of these data, it is predicted that about 5% of dichromats will be mis-classified by the Adams desat D-15 whilst under 0.1% will be mis-classified by the standard D-15. However, with the anomalous trichomats, more crossings were made on the Adams desat D-15, particularly by the milder anomals, and a diagnosis was possible in more cases. Where a diagnosis was possible, it was also correct more often with the Adams desat D-15.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330214 TI - Modelling oblique astigmatism in eyes with known peripheral refraction and optical dimensions. AB - The optical dimensions of 34 young adult eyes were measured by optical and A-scan ultrasound methods. Peripheral refraction was recorded up to field angles of 40 degrees to produce results for oblique astigmatism. These findings were modelled in schematic eyes with a monoindicial crystalline lens but with varying levels of asphericity of the optimal surfaces. PMID- 2330215 TI - The influence of age on the pattern-reversal electroretinogram. AB - Pattern reversal electroretinograms (PERGs) in response to 30' checks and 6 degree checks were recorded from 60 eyes of 30 normal healthy individuals aged between 20 and 78 years. Results were assessed to show age changes in the amplitudes and latencies of the PERGs, the ratio of 30' to 6 degree PERG amplitude, the 'N95/P50' ratio and the inter-eye ratio of the 30' PERG. The positive component of the PERG decreases in amplitude and increases in latency with increasing age. In addition, it was found that the 30' PERG/6 degree PERG ratio decreases, the N95/P50 ratio increases and the inter-eye ratio shows a greater difference between the two eyes in the older subjects. PMID- 2330216 TI - The aspherizing of intra-ocular lenses. AB - While a spherically surfaced intra-ocular lens cannot be designed to give zero spherical aberration for the whole eye, aspherizing one surface of an intra ocular lens can produce zero Seidel spherical aberration in a pseudophakic eye or set it to any desired level provided the corneal asphericity is known and this does not change with the operation. Equations for determining the asphericities are given. Asphericities for five lens shapes; the minimum spherical aberration lens and its reverse form, the equi-biconvex lens, the plano-convex lens and its reverse form are determined. The Seidel aberrations of eyes with aspherized intra ocular lenses were compared with that of eyes with spherical intra-ocular lenses. While aspherizing eliminates the Seidel spherical aberration, some residual higher order spherical aberration exists and the amount of this residual spherical aberration depends upon the lens shape. However, this residual aberration can be reduced but not made zero by modifying the asphericity. For currently used plano-convex lenses, only the curves surface can be aspherized. The effect of variations in the anterior corneal asphericity on the necessary lens asphericity was also investigated. PMID- 2330217 TI - Measurement of eye rotations in three dimensions and the retinal stimulus projection using scanning laser ophthalmoscopy. AB - A transformation algorithm is introduced to specify eye rotations in three dimensions from two-dimensional translations of ocular fundus landmarks dynamically monitored by means of the novel Scanning Laser Ophthalmoscope (SLO). The rotation parameters are expressed as Y-X-Z Euler angles and in terms of the rotation axis and one rotation angle. Additionally, the angular distance of the retinal stimulus projection can be evaluated relative to the fovea. By simultaneously operating as eye movement measurement device, fundus camera, and visual target projector, the SLO opens a variety of new applications for the combined analysis of eye movements and the underlying 'retinal events' in vision and oculomotor research. PMID- 2330218 TI - Direct, vec and other squares, and sample variance-covariance of dioptric power. AB - Matrices can be multiplied in several ways. As a result one can define a number of distinct squares of the dioptric power matrix. Additional squares can be defined for matrices vectorized by means of the vec and vech operators. These various squares can form the basis for the definition of variance and covariance of samples of dioptric powers. The complete form of the variance of dioptric powers is a 4 x 4-matrix (a variance-covariance matrix) with 10 distinct elements; four of them represent the variances of the four elements of the dioptric power matrix and the other six are the covariances between those four elements. For thin systems there are only six distinct elements of the variance covariance matrix, three of which are variances and three covariances. Examples are included that show the calculation of the different types of squares and the variance-covariance matrix for a sample of equivalent powers of thick bitoric lenses and for a sample of powers of thin systems, including conventional refractive errors. Variances calculated in the past, including those of nearest equivalent spheres and Gartner's and Churm's variances turn out to be components (or combinations of components) of the generalized variance defined here. They are valid as far as they go but they do not completely represent the dispersion of a sample of dioptric powers. The complete variance-covariance matrix does represent the dispersion fully and thus opens the way for the formal statistical analysis of measurements of dioptric power. PMID- 2330219 TI - The experience of a university-based low vision clinic. AB - An open low vision clinic has been in operation at University of Wales College of Cardiff, Department of Optometry for 5 years. This paper describes the demography and visual characteristics of 218 consecutively presenting patients. A detailed survey of the aids prescribed is conducted. A significant proportion of low vision patients required only simple aids (56.8%) and low magnification (71.6%). It is suggested that these patients could be assisted in an optometric practice. In addition, visual acuity, distance or near is not a good indicator of eventual visual performance with an LVA. Therefore, it was concluded that all patients having measurable form vision should receive a low vision assessment. PMID- 2330220 TI - Prism adaptation and viewing distance. AB - Previous studies have shown that subjects with normal binocular vision adapt to prism-induced phorias. However, there are conflicting reports as to the amount of adaptation shown to horizontal prisms. Some investigations found a greater amount of adaptation to base out prisms compared with base in, whilst others found the reverse and one study found no adaptation to base out prism at all. This study investigated the adaptation response to horizontal prisms at distance and near in a larger number of subjects (n = 40). The results confirmed our previous findings and showed that at distance the adaptation responses are asymmetrical, there being a significantly greater amount of adaptation to base out prism compared with base in, whilst at near the responses are virtually symmetrical. Possible reasons for these findings are discussed. PMID- 2330221 TI - Automatic measurement of varifocal spectacle lenses. AB - An instrument is described for the automatic measurement of lens power across the whole aperture of a varifocal lens. The apparatus is based on an electronic focimeter controlled by an external computer, which also positions the lens by two stepper motors. Methods of display of the data are discussed, and the repeatability of measurement is illustrated. PMID- 2330222 TI - The Ives visual acuity test object: a reappraisal. PMID- 2330223 TI - Analysis of three meridional keratometric measurements of the anterior cornea. PMID- 2330225 TI - Papers presented at the meeting of the Society for Experimental Optometry. Birmingham, 24-25 July 1989. Abstracts. PMID- 2330224 TI - Toroidal surface assessment by curvature measurements in three fixed meridians. PMID- 2330226 TI - Intestinal dysfunction associated with acute thoracolumbar fractures. AB - The frequency of intestinal dysfunction, particularly intestinal ileus, among patients with acute thoracolumbar fractures and no neurologic compromise was assessed. We reviewed the medical records of 70 patients who met specific criteria. Only four (6%) of these patients developed intestinal dysfunction, manifested by vomiting, abdominal distention, diminished bowel sounds, or an intestinal ileus documented by an abdominal roentgenogram. Conservative initial nutritional management of the patients did not reduce the incidence of intestinal dysfunction. This study suggests that patients with acute thoracolumbar fractures and no neurologic compromise are not at substantial risk of intestinal dysfunction and that nasogastric suction and restriction of oral intake are unnecessary in the initial management of these patients. PMID- 2330227 TI - Tips of the trade #22. Proximal tibial valgus osteotomy. A simplified technique. AB - A simplified version of a proximal tibial valgus osteotomy, reserved for cases in which the deformity is not greater than 10 degrees of valgus or the flexion contracture is not greater than 10 degrees, can be performed without the use of templates or interval fixation. PMID- 2330228 TI - Fluid and electrolyte therapy. PMID- 2330229 TI - Uric acid metabolism in children. AB - The renal excretion of uric acid in children differs quantitatively, and perhaps qualitatively, from that in adult humans. The younger the child, the greater the renal clearance of uric acid and the greater the excretion of uric acid expressed as mg per kg body weight. During infancy, the reduced ability to maximally concentrate the urine may protect against precipitation of uric acid crystals within the kidney. Conversely, the extremely high urinary uric concentrations places the very small infant at jeopardy during sudden increases in the filtered load of uric acid. Understanding the pharmacologic and physiologic modulators of renal uric acid clearance will allow the pediatrician to minimize the risk of uric acid nephropathy, and to understand the implications of uric acid in the serum or urine in children with fluid and electrolyte disorders. Certainly evaluation of serum and urinary uric acid concentrations is essential in any child with acute renal failure. PMID- 2330230 TI - Preparedness for pediatric emergencies encountered in the practitioner's office. AB - Pediatricians in the Washington, DC, metropolitan area were surveyed to assess their readiness to deal with life-threatening emergencies in their offices. Information about emergency equipment, prearranged emergency plans, advanced life support training, and emergency medical services assistance was elicited. Recommendations are made to attain appropriate levels of preparedness in all of these areas. PMID- 2330231 TI - Meconium aspiration syndrome: have we made a difference? AB - Meconium aspiration syndrome (MAS) and its associated complications are reviewed from the period before the routine use of intubation and suctioning to the present (1973 through 1987). Of the 176,790 neonates born during this period, the amniotic fluid was stained in 21,472 (12.15%). Subsequently, MAS developed in 1162 (5.41%) of the meconium-stained neonates. Male neonates were more prone to the disorder than female neonates (P = .022). There were no racial predilections for MAS. The incidence of MAS significantly decreased during the 15 years (P = .043). Of the neonates with MAS, 49 (4.22%) died as a direct consequence of the disorder. The death rate significantly declined during the study period (P = .041). Of the neonates with MAS, 345 (29.7%) required mechanical ventilation, and 134 (11.53%) had pneumothoraxes. Among neonates with MAS, the requirement for mechanical ventilation, as well as the incidence of pneumothoraxes, did not decrease from 1973 through 1987. The incidence of MAS has declined since the advent of combined obstetric and pediatric suctioning of the oropharynx and trachea. Furthermore, there are significantly fewer deaths from the disorder. These declines were likely influenced by other improvements in perinatal care, which have occurred since the early 1970s. The results do not support the contention that severe MAS and resultant deaths can be prevented altogether. PMID- 2330232 TI - Blood pressure increases, birth weight-dependent stability boundary, and intraventricular hemorrhage. AB - The blood pressure (BP) and transcutaneous PO2 (TcPO2) changes associated with intensive care procedures were evaluated to determine whether responses differ between babies with and without periventricular-intraventricular hemorrhage (PV IVH). Fifty-three inborn babies less than or equal to 1500 g were studied using a microcomputer-based monitoring system. With almost any procedure including a seemingly benign one such as a diaper change, peak systolic BP increased and TcPO2 decreased. However, responses to interventions did not differ between babies with PV-IVH and those without PV-IVH. Neither did these responses differ between those with birth weight less than or equal to 1000 g and greater than 1000 g. When each baby's record was scanned for the highest peak systolic BP before diagnosis of PV-IVH or within 48 hours in those with no PV-IVH and their BP points plotted against birth weight, a stable region was evident wherein PV IVH occurred at a lower incidence (13%). When peak systolic BP was beyond this stable region, the incidence of PV-IVH was significantly higher, 70% (P less than .0001). The stability boundary for the maximum systolic BP is birth weight dependent; the limit for the highest tolerable peak systolic BP is lower for the low-birth-weight infant. In over 70% of instances the highest peak systolic BP was associated with motor activities either induced by nursery procedures or spontaneous. We speculate that decreasing the frequency of intensive care interventions may decrease episodic BP increases to levels beyond the birth weight-dependent stability boundary where PV-IVH is likely to occur. PMID- 2330233 TI - Thalamic hemorrhage with intraventricular hemorrhage in the full-term newborn. AB - Intraventricular hemorrhage is an uncommon problem in the full-term newborn. In a review of 19 full-term infants with intraventricular hemorrhage diagnosed on computed tomography prior to 1 month of age, thalamic hemorrhage associated with the intraventricular hemorrhage was documented in 12 infants. Thus, thalamic hemorrhage appears to the most common source of intraventricular hemorrhage in this age group, particularly in infants who had uneventful birth histories and in whom clinical abnormalities (signs of increased intracranial pressure, seizures, altered level of consciousness) developed after the first week of life. The majority of these infants had predisposing factors for cerebral venous infarction such as sepsis, cyanotic congenital heart disease, and coagulopathy. The clinical appearance and outcome for infants with thalamic hemorrhage/intraventricular hemorrhage were similar to those in infants with intraventricular hemorrhage originating from other sites, except for an increased incidence of cerebral palsy in infants with thalamic hemorrhage/intraventricular hemorrhage. Definitive diagnosis was made on the basis of characteristic radiologic abnormalities. PMID- 2330234 TI - Prenatal cocaine exposure and fetal vascular disruption. AB - The question of the potential teratogenicity of cocaine has been raised by the increasing frequency of its abuse in the United States. In previous studies, an increased incidence has been documented of spontaneous abortion, placental abruption, prematurity, intrauterine growth retardation, and neurologic deficits in the infants of women who abused cocaine. More recently, it has been suggested in studies that fetal vascular disruption accompanying maternal cocaine abuse may lead to cavitary central nervous system lesions and genitourinary anomalies. In this article, 10 children born of women who abused cocaine are described, 9 of whom have congenital limb reduction defects and/or intestinal atresia or infarction. The spectrum of anomalies associated with embryonic and fetal vascular disruption accompanying maternal cocaine abuse is thus enlarged. The specific risk for congenital anomalies accompanying maternal cocaine abuse during an individual pregnancy is unknown. However, data from these patients and the available literature suggest that counseling pregnant women concerning cocaine use should incorporate warnings about the possibility of associated embryonic or fetal vascular disruption. PMID- 2330236 TI - Clinical management considerations in long-term survivors with trisomy 18. AB - As many as 90% or more of children with trisomy 18 die within the first year of life. A review of six patients with trisomy 18 documented by karyotype surviving past 1 year of age and of the trisomy 18 files of the Support Organization for Trisomy 18 and 13 indicated that a small number of children with trisomy 18 survive beyond their first year of life; a few live into their teens and twenties. In addition to medical problems that are unique to this chromosomal syndrome, these patients present complex medical problems common to all persons with chromosomal anomalies. The primary and tertiary care consultants who are able to provide knowledge and sensitive supportive care to children with trisomy 18 and to their parents are performing a service of significant benefit, no matter how brief the life span of the child may be. PMID- 2330235 TI - Effect of prenatal alcohol exposure on growth and morphology of offspring at 8 months of age. AB - In this prospective study of alcohol and other substance use during pregnancy, a cohort of women was interviewed at each trimester of pregnancy and when the offspring were 8 months of age. Data are presented concerning the outcome for 461 infants. A significant relationship was found between alcohol use during pregnancy and the growth and morphology of the offspring at the 8-month follow-up observation. Alcohol use during the second and third trimesters of pregnancy and continuous use of alcohol throughout pregnancy were significantly related to lower weight, length, and head circumference in the exposed infants at the follow up observation. A significant increase in the risk of minor physical anomalies and fetal alcohol effects was also predicted by prenatal alcohol exposure. PMID- 2330237 TI - Magnetic resonance imaging in cervical cord birth injury. AB - Three children who sustained cervical cord injury due to birth trauma are described. The clinical and radiological data, and the central nervous system pathology of one child, illustrate the advantages and feasibility of magnetic resonance imaging in ventilator-dependent children with cervical cord lesions. PMID- 2330238 TI - Effects on behavior state of prone versus seated positioning for infants with gastroesophageal reflux. AB - To evaluate the effect of positioning on behavior in infants with gastroesophageal reflux, 48 infants younger than 6 months of age (range 1.5 to 28 weeks, median 13.5) with reflux were positioned continuously prone (24 infants) or seated (24 infants) during a 120-minute postprandial period, during which behavior was monitored continuously. The prone position was associated with more sleep time, 83.5 (16 to 113) vs 43 (0 to 117) minutes, P = .01. This increase in sleep time in the prone position could be largely accounted for by a tendency toward a decrease in crying time, 19 (0 to 82) vs 38.5 (0 to 91) minutes, P = .07, which is expressed further by the significantly smaller number of prone than seated infants who cried longer than 30 minutes, P = .02. A parallel reduction in noncrying awake time in the prone vs the seated position was not significant: 15 (0-51) vs 31 (3 to 84) minutes, P = .13. PMID- 2330239 TI - Pulmonary function testing reference values and interpretations in pediatric training programs. AB - A questionnaire was sent to all pediatric training programs to evaluate the use of pulmonary function reference standards and the interpretation of pulmonary function test results. Responses were obtained from 107 of 130 institutions, and 94 of these had pulmonary function laboratories available. Of the 94, 60 used one of three reference standards. The primary reason the reference standards were chosen was either unknown or because they came with the spirometer (24), were recommended by another person or were those used in that person's training (34), or were thought to be the best standards available or most applicable to the population to be tested (31). To define abnormality, most used an 80% predicted cutoff for forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow at 25% to 75% vital capacity. For a change in an individual through time, most used a 10% change for forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow at 25% to 75% vital capacity. Thirteen used statistical methods to define abnormal individuals and none used statistical methods to define a significant change over time. Although there are a few guidelines for reference standards and interpretations of pulmonary function tests, it appears that most laboratories are not using those guidelines and that further guidelines and education are needed. PMID- 2330240 TI - Stature and weight status of children in an urban kindergarten population. AB - To assess the prevalence of growth problems among school entrants in an urban population who were not preselected on poverty or other nutritional risk criteria, we analyzed height and weight measurements for 5170 4- and 5-year-old children (91.9% black, 5.5% white, and 2.6% Hispanic) who enrolled in District of Columbia public school kindergartens in the Fall of 1985. Compared to the National Center for Health Statistics reference, the white girls and boys were of average height, Hispanic girls were of average height, and Hispanic boys were shorter than average. The black girls and boys were taller than average. In light of published evidence for black-white differences in the timing and duration of growth, we tentatively attributed this tall stature to advanced skeletal maturation of the black children relative to the predominantly white United States population growth standards. Underweight was virtually absent in this population. Excess overweight was noted in all sex-racial/ethnic subgroups, particularly among Hispanic children. However, the extent to which overweight (high weight-for-height percentile) represents obesity in kindergarten-aged children and in different racial/ethnic groups needs clarification before the implications of the finding of excess overweight can be fully understood. Overall, the growth of these children was on a par with the National Center for Health Statistics growth reference population. PMID- 2330241 TI - Changing patient management: what influences the practicing pediatrician? AB - To explore some determinants of physicians' decisions to change practice habits, we posed three questions: To what extent are some particular innovations diffused among office-based primary care physicians? What characterizes the physicians who have adopted these innovations? And, what caused them to change their behavior and adopt the innovations? Three "markers," recent innovation in medical practice, were chosen using an expert consensus technique. A telephone survey of 200 office-based pediatricians was conducted, and the physicians were asked whether or not they used the following three innovations in medical practice: continuous rather than intermittent phenobarbital for the prevention of febrile seizures, glycosylated hemoglobin measurement in the management of diabetes, and slow release theophylline in the management of asthma. The questionnaire was completed by 156 pediatricians. Of the 110 pediatricians who cared for diabetics, 73% used glycosylated hemoglobin measurement; of the 145 who saw patients with febrile seizures, 77% prescribed the continuous use of phenobarbital (if they used it at all); and, of the 152 pediatricians who cared for asthmatics, 86% reported using slow-release theophylline. The characteristics significantly associated with using the innovations were board certification, group rather than solo practice, teaching, medically related publications, academic appointment, younger age, and caring for a greater number of patients per week. For two of the innovations, discussion with a colleague was the most important source of information leading to a change of practice. The subjects cited local specialists as the colleagues who most often sparked the adoption of an innovation. PMID- 2330242 TI - Impact of eligibility criteria on phototherapy program size and cost. AB - To determine the effect of eligibility criteria on phototherapy program size and cost, 786 births in a large Health Maintenance Organization were prospectively studied. Four sets of criteria were compared, including those of the American Academy of Pediatrics and the health maintenance organization's own criteria. With all criteria sets, hospital-based phototherapy treatment was indicated for 13 (1.7%) infants and no phototherapy was indicated for 687 (87.4%) infants. Treatment varied substantially according to criteria set for the remaining 86 (10.9%) infants. From 14% to 100% of these infants would have received treatment, depending on the criteria applied; of those potentially treated, from 30% to 80% would have received home treatment. Estimated annual discretionary phototherapy costs (1985 dollars) ranged from $15,168 with the health maintenance organization criteria to almost five to six times this amount ($70,232 to $90,800) with the other criteria. Differences in costs were due mainly to the number of infants treated. This study illustrates the way in which modest variation in standards of care can potentially have a relatively large effect on medical care costs. As a case study of how health maintenance organizations reduce costs, the study shows that although the health maintenance organization anticipated costs savings due to substituting outpatient care for hospital care, most savings occurred because of a reduction in the number of infants treated. PMID- 2330243 TI - Infant temperament and school age behavior: 6-year longitudinal study in a pediatric practice. AB - We conducted a retrospective cohort study in a pediatric practice to assess the association between parents' ratings of temperamental difficulty (observations of specific infant behaviors) and perceptions of temperamental difficulty (impressions of one's infant as compared with other infants) in infancy and behavior problems at school age. Mothers of 129 infants, who had completed the Revised Infant Temperament Questionnaire at the 4-month visit, completed the Child Behavior Checklist when the child was 6 years of age. Teachers of 102 of these children completed the teacher Child Behavior Checklist. Temperamental difficulty was defined by assessments of rhythmicity, approach/withdrawal, intensity, mood, and adaptability. Initial analyses revealed that low socioeconomic status (r = -.29, P = .001), ratings of temperamental difficulty (r = .17, P = .06), and perceptions of temperamental difficulty (r = .22, P = .02) at 4 months of age were associated with increased maternal rating of behavior problems at 6 years of age (all 2-tailed tests). However, a multivariate regression analysis showed only low socioeconomic status (P less than .01) and increased perceptions of temperamental difficulty (P = .02) associated with maternal behavior problem scores. Teacher behavior problem scores were associated only with low socioeconomic status (r = -.27, P = .01). These results suggest that the link between difficult infant temperament and later behavior problems is complex and probably reflects both child factors and parent attitudes about what constitutes typical infant behavior. PMID- 2330244 TI - Postneonatal circumcision: population profile. AB - Because postneonatal circumcision includes the risk of general anesthesia and costs more than elective neonatal circumcision, a retrospective study was performed to describe the population currently undergoing postneonatal circumcision and to identify the factors influencing decisions that lead to this procedure. A chart review and follow-up telephone survey were done to gather information concerning patients admitted for postneonatal circumcision to two Salt Lake City hospitals during a 2-year period. From the 135 patients eligible for analysis, two distinct groups emerged: the "sick" group (n = 52)--those who had neonatal complications, and the "well" group (n = 83)--those with no neonatal complications. The median age at circumcision was 5.5 months for the boys in the sick group and 35 months for the boys in the well group (P less than .001, Student's t test). During the neonatal period, 32% of families in the well group received anticircumcision advice from their primary care physician. The decision in favor of circumcision was made by two thirds of the families of sick infants before their sons were 6 weeks of age. Other surgery was performed concurrent with the circumcision in 44% of patients in the sick group and 24% of patients in the well group (P less than .0001, chi 2). Balanitis, phimosis, or a physician's recommendation were listed as the primary reason for post-neonatal circumcision by 50% of patents in the well group. Phimosis was listed by the surgeon as an indication for postneonatal circumcision in 65% of all patients' charts, although only 13% of parents listed phimosis as an indication for their children's circumcision.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330245 TI - Screening adolescents for depression and parent-teenager conflict in an ambulatory medical setting: a preliminary investigation. AB - Because more than 60% of adolescent visits to physicians last less than 10 minutes, simple screening devices to identify persons at risk for social morbidity are needed. The result of a pilot screening instrument for depression and parent-teenager conflict is described. A seven-item questionnaire (three items for depression and four items for parent-teenager conflict), the Beck Depression Inventory (BDI), and the Conflict Behavior Questionnaire (CBQ), were administered to 226 adolescents at a high-risk adolescent heath center. After the visit, the provider rated each patient on a five-point Likert scale for level of depression and parent-teenager conflict. The screening questionnaire and the provider ratings were compared with the BDI and CBQ for sensitivity, specificity, and predictive value. A majority of the subjects (61% for depression and 63% for parent-teenager conflict) had no positive screening responses and, of these, less than 3% were classified as being depressed or having parent-teenager conflict by the BDI or CBQ. There were three or four positive screening responses (three responses for the depression questions and 20 responses for the parent-teenager conflict questions) among 23 adolescents and all of these scored in the abnormal range on the BDI or CBQ. Approximately one third of the subjects had intermediate responses. With one positive response, the predictive value for depression and parent-teenager conflict was 17% and 24%, respectively, whereas with two positive responses the predictive values were 56% and 26%. It was shown by receiver operating characteristic curves that the combined sensitivity and specificity of the screening questionnaire was superior to that of the physician ratings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330246 TI - Continuous hemodiafiltration in children. AB - Continuous arteriovenous hemofiltration is a form of renal replacement therapy whereby small molecular weight solutes and water are removed from the blood via convection, alleviating fluid overload and, to a degree, azotemia. It has been used in many adults and several children. However, in patients with multisystem organ dysfunction and acute renal failure, continuous arteriovenous hemofiltration alone may not be sufficient for control of azotemia; intermittent hemodialysis or peritoneal dialysis may be undesirable in such unstable patients. Recently, the technique of continuous arteriovenous hemodiafiltration has been used in many severely ill adults. We have used continuous arteriovenous hemodiafiltration in four patients at Children's Hospital Medical Center. Patient 1 suffered perinatal asphyxia and oliguria while on extracorporeal membrane oxygenation. Patients 2 and 4 both had Burkitt lymphoma and tumor lysis syndrome. Patient 3 had septic shock several months after a bone marrow transplant. All had acute renal failure and contraindications to hemodialysis or peritoneal dialysis. A blood pump was used in three of the four patients, while spontaneous arterial flow was adequate in one. Continuous arteriovenous hemodiafiltration was performed for varying lengths of time, from 11 hours to 7 days. No patient had worsening of cardiovascular status or required increased pressor support during continuous arteriovenous hemodiafiltration. The two survivors (patients 2 and 4) eventually recovered normal renal function. Continuous arteriovenous hemodiafiltration is a safe and effective means of renal replacement therapy in the critically ill child. It may be ideal for control of the metabolic and electrolyte abnormalities of the tumor lysis syndrome. PMID- 2330247 TI - Hypoglycemia in infancy: the need for a rational definition. A Ciba Foundation discussion meeting. PMID- 2330248 TI - Evaluation of children with possible appendicitis using technetium 99m leukocyte scan. AB - We evaluated the use of technetium 99m albumin colloid white blood cell (TAC-WBC) scan in 33 children with possible appendicitis. Ten children had appendicitis, four of whom had perforated their appendix at the time of surgery. Children with appendicitis differed from children without appendicitis in the incidence of right lower quadrant rebound tenderness (60% vs 17.4%), and white blood cell count (X10(3)/mm3) (14.0 + 1.9 vs 10.7 +/- 1.0). TAC-WBC scans were interpreted as either positive, negative, or indeterminate for appendiceal pathology. Twenty five children had positive or negative scans for appendiceal pathology. There were 7 true positives, 2 false positives, 16 true negatives, and 0 false negatives. This resulted in a sensitivity of 100%, a specificity of 89%, an accuracy of 92%, a positive predictive value of 78%, and a negative predictive value of 100%. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in eight children (24%), three of whom had appendicitis. The main values of TAC-WBC scan in our study of children with possible appendicitis were that it could be used emergently, it was abnormal in 100% of children with appendicitis, and it had a high negative predictive value (100%). The main limitation of TAC-WBC scan in our study was that it was indeterminate for appendiceal pathology in 24% of children. We recommend that TAC-WBC scan be used in children with possible appendicitis because it may allow outpatient management of up to 48%. PMID- 2330249 TI - Diagnosing bird fancier's disease in children. PMID- 2330250 TI - Urethral catheter knots. PMID- 2330251 TI - Evaluation of an infrared tympanic membrane thermometer in pediatric patients. PMID- 2330252 TI - American Academy of Pediatrics Committee on Bioethics: Sterilization of women who are mentally handicapped. PMID- 2330253 TI - American Medical Association Commission on Emergency Medical Services: Pediatric emergencies. An excerpt from "Guidelines for the Categorization of Hospital Emergency Capabilities". PMID- 2330254 TI - Circumcision. PMID- 2330255 TI - Adoption of hepatitis B virus-infected foreign-born children. PMID- 2330257 TI - Inadequate breast feeding and jaundice. PMID- 2330256 TI - Abdominal trauma--child abuse. PMID- 2330258 TI - [Hereditary alpha 1-antitrypsin deficiency in children]. PMID- 2330259 TI - [The Kabuki syndrome]. PMID- 2330260 TI - [Adaptation of the cardiovascular system of newborn infants in the early neonatal period (data of echocardiography with phasic analysis of cardiac activity]. PMID- 2330261 TI - [Effect of viral and bacterial infections on the pituitary-thyroid activity in infants]. PMID- 2330262 TI - [Status of immunity in children with hyposiderosis and the incidence of infectious diseases]. PMID- 2330263 TI - [Functional state of the central nervous system in children with bronchial asthma in the post-paroxysmal period]. PMID- 2330264 TI - [Study of the formation of intestinal microflora in newborn infants staying with or separated from their mothers]. AB - In children of the first month of life, the formation of normal intestinal microflora was studied depending on whether they stayed with mothers or alone in the maternity home. Thirty healthy neonates born to young healthy mothers with a history of a favourable course of pregnancy which progressed to the delivery via the natural maternal passages were examined. Intestinal microbiocenosis in the newborn turned out more physiological provided they were placed at the "mother child" department as compared to that when the newborn stayed alone. Organization of the joint staying of mothers and children in the wards of the maternity home increases the colonization resistance of the newborn, favours normal adaptation and may be one of the factors bringing about the diminution of the rate of pyoseptic diseases in the newborn. PMID- 2330265 TI - [The role of Chlamydia infection in the development of infectious inflammatory diseases in premature newborn infants]. AB - It is highly probable that neonates may be infected with chlamydiae provided their mothers are chlamydia carriers, especially in disease exacerbation before delivery. Parallelism was noted between the intensity of antigen demonstration in the mother and the child. Infection with chlamydiae potentiates secondary infectious inflammatory diseases in premature neonates. However, diseases of chlamydia etiology developed only in 20.5% of children of all the infected and manifested themselves by pneumonias or total toxicosis without any localized focus of infection. PMID- 2330266 TI - [Characteristics of cellular immunity in newborn infants with intestinal bacterial infection after administration of lysozyme]. AB - Two comparable groups made up of 15 neonates with intestinal infections induced by opportunistic bacteria were under observation. The children of group 1 received lysozyme in a dose of 25 mg/kg a day for 7-10 days together with conventional therapy Lysozyme appeared to promote the reduction of the disease duration and the rise of the phagocytic reserves of peripheral blood neutrophils in the children examined. PMID- 2330267 TI - [Effect of perinatal pathology on the morphofunctional status of the pituitary and adrenal glands in newborn infants]. AB - A comprehensive study of the content of hormones (ACTH, STH and hydrocortisone) directly in the cells of endocrine organs (pituitary) and in the blood of the dead newborn was conducted for the first time, using immunocytochemistry and radioimmunoassays. Based on the findings obtained, the degree of maturity of adnenocorticotropic function of the pituitary was established as were adaptation reserve potentiatialities of endocrine functions in the newborn, bearing in mind the gestation age, the influence of the mother's infectious disease (chronic pyelonephritis, rheumatic fever, bronchopulmonary pathology), and the time of the child's life. PMID- 2330268 TI - [Effect of chronic intrauterine hypoxia on purine compound metabolism in the erythrocytes of newborn infants in the early neonatal period]. AB - The content of purine compounds in red blood cells was measured and compared in 21 neonates with a history of chronic intrauterine hypoxia, depending on the condition at birth and the early period of adaptation. The content of purine compounds in whole blood was measured at the moment of birth and on days 1, 3 and 5 of life. It has been disclosed that the pattern of purine metabolism abnormality in funic red blood cells makes it possible to predict the course of the early period of adaptation. Changes in the content of hypoxanthine and inosine monophosphate appeared to be most remarkable. PMID- 2330269 TI - [Effect of intranatal asphyxia on the pattern of psychomotor development of children up to 7 years of age]. AB - The paper is concerned with the psychophysical development of 460 children born in asphyxia of varying gravity. The establishment of psychomotor functions was traced over time, since the moment of birth to 7 years. The highest rate of complications was diagnosed in children aged 6-7 years. It should be mentioned, however, that gross disturbances were primarily detected at an early age, whereas at a late age different intellectual abnormalities were diagnosed. Children with a history of grave asphyxia need rehabilitation treatment aimed at the recovery of psychomotor functions. PMID- 2330270 TI - [Osteocalcin in infants with rickets]. AB - Infants afflicted with rickets demonstrate a reduction in the blood content of vitamin K-dependent protein, osteocalcin, most pronounced in disease of medium gravity, in its calcipenic and phosphopenic varieties. It has been established that there is an inverse correlation between osteocalcin content and the level of parathyroid hormone and a direct correlation between osteocalcin content and the concentration of total and ionized calcium and calcitonin in the blood. It is suggested that measurement of blood osteocalcin in children may serve a diagnostic marker of metabolic disorders and mineralization of osseous tissue. PMID- 2330271 TI - [Clinical significance of ultrastructural disorganization of cell membranes in hypotrophy]. AB - The authors describe the results of studying lipid peroxidation and ultrastructure of blood cells in children aged 1 month to 2 years, suffering from chronic distress of nutrition of the hypotrophy type. Appreciable disorders of the membranes of blood cells and their organoids were found, related to activation of free radical lipid oxidation in diseased children. The relationship was noted between destructive changes in the ultrastructure of the biological membranes and the disease gravity, duration of the effect of the high content of lipid peroxidation products on cellular and subcellular membranes. The disorganization of the membrane ultrastructure in the body of patients with hypotrophy is an important component in the disease pathogenesis and requires administration of membrane-stabilizing therapy in a complex of treatment measures. PMID- 2330272 TI - [Roentgenologic diagnosis of congenital hypertrophic pyloric stenosis]. AB - In 1983-1988, in the city of Minsk 196 patients with congenital hypertrophic pylorostenosis (CHRS) were under treatment. The mean CHPS incidence is 1.06 per 1,000 neonates. X-ray examination was performed in 170 cases. CHPS was excluded by error only in one case (0.5%) on day 3 of the disease. In 8 cases, compensated pylorostenosis was diagnosed. It was characterized by proper evacuation from the stomach and positive dynamics of the body weight at the moment of examination. It is suggested that CHPS develops in response to the enhancement of hydrochloric acid secretion. The study points to the high efficacy, simplicity and safety of the method proposed. PMID- 2330273 TI - [Various clinico-immunologic and biochemical indicators in infants with suppurative septic diseases]. AB - The authors provide the results of studying some characteristics of immunity and lipid peroxidation (LPO) in babies (n-123) with pyoseptic diseases. The changes in the immune status and LPO seen in children with pyoseptic diseases reflect the gravity of the clinical status, being an objective criterion in the all-round assessment of the treatment efficacy and prediction of the pathological process. These changes also form the basis for institution of the pathogenetic correction and rehabilitation therapy. PMID- 2330274 TI - [Echocardiographic study of the heart in children with mitral valve prolapse and connective tissue dysplasia]. AB - Altogether 125 children with connective tissue dysplasia and mitral valve prolapse were subjected to clinical and echographic examinations. Dilation of the aortic root, elevation of pulmonary artery pressure and derangement of myocardial contractility were discovered. These disorders occurred as a result of disseminated connective tissue abnormalities. It is noted that children with connective tissue dysplasia and mitral valve prolapse require prophylactic medical examination because of progressive alterations on the part of the cardiovascular system with age. PMID- 2330275 TI - [Echocardiography in the evaluation of central and intracardiac hemodynamics in children with mitral valve insufficiency]. PMID- 2330276 TI - [Prevalence and characteristics of the development of allergic reactions to food products of plant origin in children with pollinosis]. PMID- 2330277 TI - [Correction of metabolic changes in neutrophils with carnitine chloride in newborn infants at risk of developing bacterial infections]. PMID- 2330278 TI - [Heparin in the treatment of suppurative meningitis in newborn infants]. PMID- 2330279 TI - [The health of newborn infants as a microbiological problem]. AB - The data provided are concerned with the etiological relation of the gravest pyoseptic infections in children of the first months of life, including cases of intrahospital epidemic outbreaks, to the disturbances in microflora formation and colonization of the intestine of the newborn staying at obstetrical and children's hospitals with hospital strains of gram-negative bacteria possessing multiple drug resistance (primarily K. pneumoniae, E. coli, S. marcescens, P. aeruginosa). The microbiological approach to the prevention of pyoseptic infections in children of the first year of life should guarantee that neonates are supplied with sources of normal body microflora and that the control is exercised over the spreading of hospital bacterial strains in obstetrical and children's hospitals. PMID- 2330280 TI - [Effectiveness of combined laser therapy of rheumatoid arthritis in children]. PMID- 2330281 TI - [Practical activities of a pediatrician and the tasks of postgraduate training]. PMID- 2330282 TI - [Elaboration of qualification characteristics of a pediatrician for certification of the qualification categories]. PMID- 2330283 TI - [Development of clinical thinking of a subintern on the topic "Gastroenterology in children"]. PMID- 2330284 TI - [A method of complex treatment of secondary hypogalactia]. PMID- 2330285 TI - [Role of CT in evaluation of the extension of pancreatic cancer]. AB - CT findings of 39 lesions from 37 cases of pancreas cancer were correlated with surgical and/or pathological findings. Each finding was recorded following "General rules for surgical and pathological studies on cancer of pancreas" proposed by Japanese pancreatic society. CT employed in this study is Somatom II (Siemens) with scan time of 5 seconds and slice thickness of 8 mm. Contrast study with bolus injection of contrast medium is a basic procedure in all the cases. The results are as follows: 1) T factor (size of the tumor) was underestimated in 9 lesions, no overestimation was observed. It is because that the contrast enhancement surrounding low density was not included in the size of the tumor. 2) No positive results were observed in lymph node group of #17, but many false positives in #12. Results of diagnosis of lymph nodes metastasis was poor, the total accuracy was 65.5%. 3) CT was very effective in the diagnosis of V factor, total accuracy was 95.5%. 4) In S (serosal invasion) and RP (retroperitoneal infiltration) factors, the total accuracy was 81.0%, and 87.1% respectively, when the protrusions into and the disappearance of the surrounding fat plane were taken into account. 5) CT is not effective in the diagnosis of CH (bile duct invasion) factor, because of non-differentiation between compression and invasion from the surrounding pancreas tumor. 6) Results of CT were good in Du (duodenal invasion) factor. 7) Finally, it was concluded that CT is effective in the staging diagnosis of pancreatic cancer. PMID- 2330286 TI - [Transcatheter arterial embolization therapy in cases of recurrent and advanced pelvic cancer--estimation by Cox's proportional hazard model]. AB - From April 1983 through September 1988, transcatheter internal iliac arterial embolization therapy (TAE) using Gelfoam particles was performed in 36 patients with recurrent pelvic cancer and 18 patients with advanced pelvic cancer. The tumor showed complete response (CR) to the therapy in seven patients, partial response (PR) in 18, minor response (MR) in five, and no change (NC) in 24 patients, with the response rate (CR + PR) of 46.3%. Univariate analysis, using Kaplan-Meier estimates and log-rank test, revealed that overall survival was related to performance status (p = 0.0001) and tumor reduction by TAE (p = 0.0008). Similarly, a multivariate analysis, using Cox's proportional hazard model, revealed a strong relationship between prognosis and performance status and tumor reduction by TAE. These results show that both good general condition and tumor reduction by TAE are significant characteristics for the prognosis of recurrent and advanced pelvic cancer treated by TAE. PMID- 2330287 TI - [Bone changes in congenital biliary atresia--review of 42 cases after surgery]. AB - Plain radiographs of forty-two infants with biliary atresia were reviewed to clarify the clinical significance of bone changes after surgery. The same surgical procedures (hepatoportojejunostomy with Suruga II enterostomy or choledochojejunostomy with Suruga II enterostomy) were performed in all cases except one at Juntendo University Hospital during 1977-1983. Bone changes were found in thirty-one patients during the 2 year period after surgery, and generalized osteopenia was the common radiological manifestation. In addition, sixteen patients were revealed to have rickets and/or fractures. The age of development of osteopenia ranged widely, but that of rickets and fractures ranged from 6 months to 2 years. It corresponded well to the age of recovering from physiological depression of bone mineral content in normal infants. Most rickets and fractures developed in association with other complications such as pulmonary infections. They were healed with treatment within 2-3 months after onset. But osteopenia persisted longer in most cases. Compared to cases without bone changes, jaundice was seen more frequently and the prognoses was worse in cases with bone changes. There was no relationship between rickets or fractures and prognosis. Biochemical data at the onset of bone changes included hypoalbuminemia and hypophosphatemia. Hypoalbuminemia, hypophosphatemia and hypocalcemia were seen in cases with rickets or fractures. But hypocalcemia was improved with treatment. From these observations, we considered that osteopenia reflected well the patients' general condition and prognosis, but most rickets or fractures which developed due to failure to meet the physiological high demand of calcium, did not play a major role for prognosis of biliary atresia. PMID- 2330288 TI - [Clinical evaluation of renoscintigraphy using 123I-orthoiodohippurate- comparison with 131I-OIH and measurement of the effective renal blood flow]. AB - Renoscintigraphy using 123I-orthoiodohipprate (123I-OIH) was conducted, and the dynamic imaging study results and the renograms were analyzed. The results using 123I-OIH were compared with those using 131I-OIH in 22 of 33 patients. Measurement of the effective renal blood flow (ERBF) was also performed using 123I-OIH by the single blood-sample method. 123I is a more suitable nuclide for gamma-camera scintigraphy than 131I in terms of physical characteristics, and a larger dose of 123I-OIH is possible than 131I-OIH because of its lesser radiation. These are the reasons why clearer dynamic images of the blood flow phase, functional phase and excretion phase can be obtained. These make possible diagnoses associated with the organic changes and functions. No essential differences could be found in the functional study results of renogram between the two drugs because on the nuclide of 131I is replaced by 123I, but a renogram with less statistical noise could be obtained using 123I-OIH than 131I-OIH. The radiation dose of 123I-OIH is less than that of 131I-OHI, and clearer dynamic images and functional indexes can be easily obtained in scintigraphy using 123I OIH. It is concluded that 123I-OIH is a useful radiopharmaceutical for renal examination, and it should replace 131I-OIH. PMID- 2330289 TI - [The experience of a new double-catheter introducer for simultaneous bilateral internal iliac angiography]. AB - We developed a new 8F catheter-introducer system designed for simultaneous insertion of two catheters into each internal iliac artery via a single puncture. This introducer has a common distal limb and a pair of proximal limbs connected in a Y-shaped fashion. Each of the proximal limbs has its own check valve and flushing side arm, through which one can pass two catheters separately. We succeeded in placing each of two catheters at desired sites in three cases of pelvic angiography. This system will be of great help in pelvic angiography and infusion-chemotherapy when bilateral catheterization is required. PMID- 2330290 TI - [New oral contrast material for gastrointestinal MR examination--green tea mixed with sodium alginate]. AB - We found incidentally the stomach filled with the material of high signal intensity on T1 weighted images. The material was a mixture of green tea and sodium alginate (drug for peptic ulcer). We proved that T1 and T2 were significantly shortened by the mixture in the experimental study. This was successfully used for the patients. PMID- 2330291 TI - [Usefulness of assessing bone mineral content of cortical bone in patients with lingering imbalance of bone metabolism]. AB - The CT numbers of cortex at the level of 20 cm (CT20) and of spongiosa in the lateral condyle at 2 cm (CT02) proximally from the distal end of the femur, and the bone mineral density of spongiosa in L3 body (BMD), were obtained by QCT. The study included 48 patients with rheumatoid arthritis or chronic renal failure as well as 10 healthy volunteers. The relationships of CT20 vs BMD in the regions above and below a critical value of BMD were quite different from each other. Similar relationships were observed in the plot of CT20 vs CT02. The results indicated that the demineralization of cortex was much less than that of spongiosa while the mineral content of spongiosa kept higher than a critical value, but the demineralization of cortex surpassed that of spongiosa once the mineral content of spongiosa had become lower than the critical value. It is necessary to assess bone mineral content of cortex especially in patients with lingering imbalance of bone metabolism. PMID- 2330292 TI - A time to listen. PMID- 2330293 TI - Dangerous economies. PMID- 2330294 TI - Carry on matron. PMID- 2330295 TI - Racism in nursing. PMID- 2330296 TI - One day at a time. PMID- 2330297 TI - Setting standards. A staff-centred approach. PMID- 2330298 TI - The lessons of nursing beds. PMID- 2330299 TI - A nurse in need. PMID- 2330300 TI - Essentials of management. Getting the most from the team. PMID- 2330301 TI - Psychological effects of resettlement. PMID- 2330302 TI - Chemotherapy support. PMID- 2330303 TI - Interpersonal skills: a smallest space analysis. PMID- 2330304 TI - Nurse education issues--problem-based learning. PMID- 2330305 TI - Catheter prescribing and the use of antimicrobials. PMID- 2330306 TI - Crack babies. PMID- 2330307 TI - Discharging duties. PMID- 2330308 TI - Working at health. PMID- 2330309 TI - Practising change. PMID- 2330310 TI - Word power. PMID- 2330311 TI - Helping hands: a glimpse into the future. PMID- 2330312 TI - Helping hands: vocational support. PMID- 2330313 TI - Helping hands: 'we can do that'! PMID- 2330314 TI - Essentials of management. Team work and leadership. PMID- 2330316 TI - Research on the elderly. PMID- 2330315 TI - Renal dialysis and mood swings. PMID- 2330317 TI - Self-medication for elderly patients. AB - This paper describes the introduction of a self-medication programme for elderly in-patients using action research. The programme was initiated by a steering group which met regularly to implement and monitor self-medication. Ward staff were interviewed to assess their learning needs before the start, meetings were held as the project advanced, and a final staff evaluation questionnaire was administered. Patients' opinions were also monitored. Self-medication was successfully introduced and minor problems were rapidly solved by participating staff. Patients were highly satisfied with the new independence and self-esteem they had gained through taking their own medications. Nurses shared these feelings, but also felt that self-medication was more time consuming than previous drug rounds. Suggestions for further research and development are given. PMID- 2330318 TI - AIDS unit nurse 'told to take HIV test'. PMID- 2330319 TI - Autogenics--neighbourhood venture. PMID- 2330320 TI - Factors in appraisal of chronic illness. PMID- 2330321 TI - Identifying the alcohol misuser. PMID- 2330322 TI - Continence: turning the tide. PMID- 2330323 TI - Continence: help for the elderly confused. PMID- 2330324 TI - Continence: a new regional model. PMID- 2330325 TI - Continence: playing a central role. PMID- 2330326 TI - Production of epidermal growth factor and transforming growth factor-alpha by the androgen-responsive LNCaP human prostate cancer cell line. AB - Epidermal growth factor (EGF)-related polypeptides may be involved in the growth of human prostate cancer cells, and in the androgen stimulation of hormone responsive prostatic carcinomas. We have shown that androgen-responsive LNCaP cells, like the autonomous DU 145 human prostate cancer cell line, synthesize and secrete EGF and related polypeptides, including immunoreactive transforming growth factor-alpha (TGF-alpha). As determined by radioimmunoassay, intracellular EGF levels were approximately 100 times those of TGF-alpha, but together these accounted for less than half of the total EGF-like polypeptides detected in a radioreceptor assay. Although LNCaP cell growth was stimulated by dihydrotestosterone (DHT), there was no evident effect on immunoreactive EGF levels in the medium after correction for cell number. Moreover, metabolic labeling experiments showed no effect of the androgen on EGF synthesis by LNCaP cells. Gel filtration chromatography of conditioned medium showed both high molecular weight species and the mature 6,000 dalton form of immunoreactive EGF. We conclude that although LNCaP prostate cancer cell growth is stimulated by DHT, it is unlikely that it is mediated directly via increased EGF synthesis by the tumor cells. PMID- 2330327 TI - Prostate cancer occurring in identical twins: a case report. AB - Prostatic cancer, which is an age-associated and androgen-dependent cancer, is the most common malignancy in males in the United States. Although the etiologic factors in prostate cancer are not clear, increased male sexual activity on a hormonal basis, a viral-venereal connection, and air pollution have been hypothesized. Genetic factors are suggested by racial variation and by familial incidence of prostate cancer; however, with family studies alone, it is not possible to decide if it is genetically determined or if it is due to a greater than average similarity in environment. For cancer in general, the study of concordance rates among populations of twins has failed to establish a precise role for inheritance, but more detailed study of individual types of tumors in twins may reveal a genetic connection. The following report describes the second recorded monozygotic twin set concordant for prostate cancer. PMID- 2330328 TI - Effects of various feeding regimens on reproduction in broiler-breeder males. AB - A study was conducted using commercial broiler-breeder males and females maintained in all-litter pens allowed to mate naturally. Using a separate feeding arrangement, males were given a diet containing either 12% or 14% protein. Body weights were maintained at either 90% or 100% of the recommended level. Females were provided feeders with grills which denied males access to the feed, while male feeders were elevated 46 cm above the floor to deny female access to that feed. In control pens, males and females ate from the same feeders and received a breeder diet with 14% protein. Eggs produced in pens where the males and females were fed separated showed significantly higher fertility (4.2%) than eggs from control pens. No differences in percentage fertility were noted between the two dietary-protein levels or body-weight groups of males fed separately. Furthermore, no differences were measured in percentage hatch of fertile eggs among any of the treatment groups. Males in control pens showed significantly heavier body weights and breast-angle measurements starting at 32 and 40 wk of age, respectively. No treatment effect was measured for male pododermatitis. The male control birds had heavier testes weights than the males in the groups with restricted body weights. However, semen concentration was not affected. This indicates that the improved fertility was related to the size and weight of the males, not to their ability to produce semen. The reduced fertility associated with excess male body weight may be both physical and physiological in nature. PMID- 2330329 TI - Changes in tissue mineral concentrations associated with sudden-death syndrome in chickens. AB - The relationship between mineral elements and sudden-death syndrome (SDS) in chickens was investigated. Tissue from the heart, liver, lung, and kidney was obtained from 22, male broiler chickens that had died of SDS and from 32, healthy male chickens. The samples were analyzed semiquantitatively for 68 elements by inductively coupled, plasma mass spectrometry. The differences in the concentrations of Br, Ca, Fe, Ge, Mg, Mn, P, Rb, Sr, and Zn between healthy and SDS chickens in one or more of the tissues were found to be very highly significant (P less than or equal to .0001). PMID- 2330330 TI - Breeding-hen and progeny performance when hens are fed excessive dietary zinc. AB - Short-term (12 wk) and long-term (44 wk) studies were conducted to observe the effects of excessive Zn supplementation on the performance of breeding hens and their progeny. Zinc sulfate was added to a corn-soybean meal diet containing 28 mg of Zn/kg in order to provide Zn supplementation at 0, 20, 200, and 2,000 mg/kg. Each dietary treatment was fed to two groups of 20, Single Comb White Leghorn hens and one New Hampshire rooster. The hens were 56-wk old at the start of the short-term study and 24-wk old when the long-term study began. Determinations were made for: fertility, hatchability, progeny growth to 3 wk of age, Zn-related feather-fraying among the progeny as well as Zn, Cu, and Fe in the liver, pancreas, and right tibiotarsus. The Zn treatments had no effect on hen performance or on reproductive performance. Even though Zn was considerably elevated and Cu was reduced in the eggs collected from hens fed the highest level of Zn, chick performance and the tissue content of Zn, Cu, and Fe were not influenced by the maternal Zn nutritional status. PMID- 2330331 TI - Absorption and bioavailability of DL-methionine hydroxy analog compared to DL methionine. AB - Intestinal absorption of crystalline DL-methionine (DL-MET) and DL-methionine hydroxy analog calcium (DL-HMA) were determined in a true-digestibility-balance assay using cecectomized (CEC) and sham-operated conventional (CONV) cockerels. The treatments consisted of fasted birds and birds crop-intubated (CI) with 30 g of a corn-soybean meal basal diet (16% CP) supplemented with 0, .2, or .4% of DL MET or equimolar levels of DL-HMA. There was no detectable free D-MET or L-MET or HMA in the excreta of fasted birds or of those fed the unsupplemented basal diet. The intestinal absorption of DL-HMA was 95.9 +/- .8% (means +/- SE) for CEC and 98.8 +/- .8% for the CONV cockerels. The absorption of DL-MET was approximately 99.7 +/- .2% for the CEC and the CONV cockerels. In a second experiment procedures were developed for a bioavailability assessment by comparing the growth responses to CI and intraperitoneal-injected (IP) DL-MET or DL-HMA in chicks fed a crystalline-amino-acid diet deficient in methionine. Graded increments of pH-adjusted DL-MET or DL-HMA (in water solutions) were administered twice daily in a 7-day growth assay. Slope-ratio analysis indicated that bioavailability (+/- SE) of CI DL-HMA was 91.3 +/- 11.8% relative to the CI DL MET on an equimolar basis. The bioavailability of CI DL-HMA was similar to that of IP DL-HMA, indicating that the intestinal absorption of DL-HMA was highly efficient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330332 TI - Follicular control of oviposition in the hen. AB - Ligation of the largest preovulatory follicle (F1) or the second largest preovulatory follicle (F2) delayed terminal oviposition for at least 2 h. Ligation of the fourth or fifth largest preovulatory follicle had no effect on the time of terminal oviposition. The conclusion reached was that some factor produced by the most mature follicles in the ovarian hierarchy influenced the timing of oviposition. Since the terminal oviposition occurs independently of ovulation, the authors concluded that the influence of the F1 and F2 follicles was independent of any preovulatory endocrine changes. PMID- 2330333 TI - Accumulation and distribution of ions of group-IIIA elements in the tissues and eggs of the Japanese quail. AB - Solutions of salts of the five Group-IIIA elements were given, intravenously, to mature Japanese quail. By 18 h, the accumulation maxima in the major tissues were: leg bones, 20% for Ga+3 (67Ga label) in estradiol-treated males; liver, 51% for Al+3 (26Al label) in control males; kidneys, 32% for In+3 (114mIn label) in estradiol-treated males; and growing oocytes plus ova, 37% for In. Accumulations of Tl+1 (202Tl label) were 6 times those for Ga or In in the brain and muscles, and .1 times in plasma. The cumulative maxima in egg components over 8 (B; Tl) or 10 (Al; Ga; In) days were B, 23% in albumen; Al, 38%, Ga 27%, In, 43% in yolks; Tl, 12% in shells. The accumulation of thallium in the eggshells markedly exceeded (P less than .001) the deposits of the other IIIA elements in shells, Al being the next highest at .54%. PMID- 2330334 TI - Effect of high-energy electron irradiation of chicken meat on thiobarbituric acid values, shear values, odor, and cooked yield. AB - Experiments were conducted to determine whether electron-beam irradiation would affect shear values, yield, odor, and thiobarbituric acid (TBA) values of chicken tissues. Broiler breasts (pectoralis superficialis) and whole thighs were irradiated with an electron-beam accelerator at levels to produce adsorbed doses of 100, 200, and 300 krads on the surface of the sample. The thigh samples were stored for 2, 4, and 8 days before testing for TBA values. The depth to which the radiation had penetrated the pectoralis superficialis muscle was also determined. Radiation penetrated 22 mm into slices of pectoralis superficialis muscle when 100 krad was absorbed by the surface of the tissue. The dose absorbed beneath the tissue surface to a depth of 10 mm was larger than the dose absorbed at the surface. The absorbed dose decreased as the depth of penetration increased. For cooked breast tissue, the shear values and moisture content were not affected by the absorbed radiation. Cooking losses of aged breast tissue were not affected by irradiation, but cooking losses were reduced in breast tissue that had not been aged. Irradiating uncooked thigh and uncooked breast samples produced a characteristic odor that remained after the thighs were cooked but was not detectable after the breast samples were cooked. With two exceptions, no significantly different TBA values were found that could be attributed to irradiation. PMID- 2330335 TI - Protein quality and iron bioavailability of mechanically and hand-deboned turkey meat fed to rats. AB - The protein quality and iron bioavailability of mechanically deboned turkey meat (MDT) and hand-deboned turkey meat (HDT) were determined in rats. The protein, fat, and moisture levels in MDT were similar to those found in HDT. The MDT, however, contained more ash, calcium, and iron than the HDT. The MDT and HDT had similar amino-acid patterns; methionine and cystine were the limiting amino acids for both products. The amino-acid scores were .97 and .98 for MDT and HDT, respectively. The protein efficiency ratio and biological value as well as the values for net protein utilization and nitrogen efficiency for growth for MDT were similar to those for HDT and reference casein (P greater than .05). The hemoglobin-regeneration efficiency values were 40, 39, and 55%, respectively, for MDT, HDT, and FeSO4 (least significant difference = 12%). The MDT contained more bioavailable iron (7.6 mg of iron per kg of meat or 4.1 mg of iron per 1,000 kcal) than the HDT (4.2 mg/kg or 2.4 mg/1,000 kcal). Mechanically deboning turkey meat did not affect its protein quality, but increased the amount of bioavailable iron. PMID- 2330336 TI - In vitro inhibition of arterial myocyte growth and stimulation of low density lipoprotein metabolism by SIM 6080, a new calcium antagonist. AB - We have investigated the in vitro effect of the new calcium antagonist SIM 6080 on proliferation of rat aortic smooth muscle cells and on LDL receptor-mediated catabolism in human fibroblasts. Verapamil was used as the reference compound. SIM 6080 inhibited the proliferation of rat aortic myocytes in concentrations ranging between 1 and 20 microM. The inhibition, evaluated as cell number and nuclear incorporation of [3H]thymidine, was dose and time dependent; the cell doubling time increased with drug concentrations up to 69 h versus 20 h for controls. Similar results on both LDL pathway and smooth muscle cell proliferation were achieved with verapamil, but higher concentrations were needed. The specific uptake and degradation of 125I-LDL was evaluated in human fibroblasts after 48 h incubation with SIM 6080 (1-10 microM). The compound dose dependently enhanced the receptor-mediated 125I-LDL uptake, with a fourfold increase as a maximal effect (10 microM); LDL degradation was less sensitive to the drug. The present results provide evidence that the new calcium antagonist SIM 6080 interferes in vitro with processes involved in atherogenesis. PMID- 2330337 TI - Stimulation of low density lipoprotein receptor activity in liver membrane of guggulsterone treated rats. AB - Chronic feeding of guggulsterone to rats showed hypolipidaemic activity in blood serum and liver membrane lipids. The decrease in serum cholesterol is associated with enhanced uptake of LDL by the liver through receptor mediated endocytosis, located on the surface of the cell membrane. In the present communication it has been shown that membranes prepared from liver of guggulsterone treated rats exhibit up to 87% increase in binding sites for human 125I-LDL. Significant decrease in lipid levels of serum as well as of membrane were observed. Lipid lowering activity of the drug in relation to LDL catabolism and other possible mechanisms have been explained. PMID- 2330338 TI - Effect of cold-restraint stress on glutathione and lipid peroxide levels in the liver and glandular stomach of rats. AB - The effect of starvation and cold-restraint stress on glutathione and lipid peroxide levels in the liver, stomach and plasma of rats was investigated. Hepatic and gastric glutathione levels were significantly decreased in starvation and cold-restraint groups when compared with values obtained from the control group. In both tissues, lipid peroxide levels were significantly decreased after starvation but were not significantly different from control values after cold restraint treatment. However, when compared with the values obtained from the starvation group there was a significant increase in both hepatic and gastric lipid peroxide levels after cold-restraint. Plasma lipid peroxide levels were slightly decreased in the starvation group and significantly increased in the cold-restraint group. Our results suggest that pathological consequences of stress on different tissues could be due to stimulation of lipid peroxidation. PMID- 2330339 TI - Effect of aspirin and indomethacin on the serum and urinary calcium, magnesium and phosphate. AB - Recent data have shown that administration of prostaglandin inhibitors to patients with hypercalciuric nephrolithiasis decreased urinary calcium excretion, implying a possible role for prostaglandins in calcium excretion. To explore this hypothesis, we investigated the effect of single dose or 7 days' administrations of aspirin (100 mg/kg orally) or indomethacin (20 mg/kg, orally) on the urinary and serum concentrations of calcium, magnesium and inorganic phosphate. Experiments were performed in normocalcaemic and hypercalcaemic rats. Hypercalcaemia and hypercalciuria were induced in male Wistar albino rats by administration of vitamin D3 (20,000 IU/daily) for 7 days. Aspirin and indomethacin both significantly lowered the urinary calcium excretion in normocalciuric and hypercalciuric rats. The acute administration of indomethacin caused greater reduction of calcium excretion than that produced by the acute administration of aspirin, whereas aspirin showed greater activity than indomethacin after the long-term use of each. Aspirin induced hypocalcaemia in normocalcaemic rats and abolished the hypercalcaemia in hypercalcaemic rats. On the contrary, indomethacin, a specific prostaglandin biosynthesis inhibitor, increased serum levels of calcium. Hypophosphataemia was observed only after the administration of a single dose of aspirin in normocalcaemic rats, while the reduction of urinary phosphate excretion was investigated in hypercalciuric rats after the acute and chronic administration of indomethacin. Serum levels of phosphate were not altered significantly by acute or chronic administration of indomethacin. A single dose of indomethacin significantly reduced urinary excretion of magnesium in both groups of rats. However, the acute and chronic administration of aspirin resulted in non-significant changes in serum and urinary concentrations of magnesium. These data suggest that aspirin has hypocalcaemic and hypocalciuric actions while indomethacin has only a hypocalciuric effect. Aspirin may produce these actions by two mechanisms, one of them like that of indomethacin which is dependent on the inhibition of biosynthesis of prostaglandins, and another possible mechanism that is not related to the inhibition of prostaglandin biosynthesis. This suggestion may be supported by the discrepancy between the effects of aspirin and indomethacin on the renal handling and serum concentrations of magnesium and inorganic phosphate. PMID- 2330340 TI - Differential effects of central and peripheral cholinergic blockade on water consumption by rats. AB - Atropine (5 mg/kg, s.c., twice daily) had no significant effect on 24-h water consumption on day 1 of treatment; on subsequent days the rats showed a significant increase. Procyclidine (5 mg/kg, s.c., twice daily) had a similar effect, except that the increase in daily water consumption began on the third day of treatment. Methylatropine (5 mg/kg, s.c., twice daily) markedly depressed water consumption on day 1; from the second day on no significant effects on 24-h water consumption were seen. The results suggest that the dipsogenic actions of cholinergic blocking agents on 24-h water consumption involve central rather than purely peripheral actions. PMID- 2330341 TI - Characterization of the effects of adenosine, adenosine 5'-triphosphate and related purines on acid secretion in isolated rabbit gastric glands. AB - The influence of adenosine, AMP, ADP, ATP, the adenosine analogue L-PIA and the ATP analogue beta,gamma-methylene ATP, on gastric acid secretion, as measured by the aminopyrine accumulation method, in resting and histamine-stimulated glands isolated from rabbit gastric mucosa was studied. In resting glands, adenosine and its analogue L-PIA (10 microM-1 mM) caused significant concentration-related increases of the basal H+ secretion, whereas no changes were obtained in response to the other purines tested. In histamine-stimulated glands, adenosine, L-PIA and AMP (10 microM-1 mM) induced concentration-related increases of the H+ secretory rate, whereas ATP, beta,gamma-methylene ATP and ADP (10 microM-1 mM) produced concentration-related decreases of the H+ raised rate. The rank order of potency of the purine compounds in increasing the stimulated H+ secretion was: adenosine greater than L-PIA much greater than AMP, and in decreasing it was: ATP much greater than ADP greater than beta,gamma-methylene ATP. The stimulatory responses to adenosine were inhibited by theophylline (10 microM-100 microM) and caffeine (10 microM-1 mM); whereas, the inhibitory responses to ATP were significantly reduced by the well known prostaglandin synthesis inhibitor indomethacin (1 microM-100 microM). From the results it is concluded that in isolated rabbit gastric glands, purine compounds are effective modulators of the gastric H+ secretory process. The pattern of purine activity obtained suggests that the stimulatory responses, inhibited by methylxanthines, may be mediated via P1 purinoceptors, while the inhibitory responses, reduced by indomethacin, may be mediated via P2-purinoceptors. PMID- 2330342 TI - Influence of desipramine on the contractile responses to noradrenaline, clonidine and to electrical field stimulation in the rat isolated seminal vesicle. AB - The effect of desipramine (DMI) on the contractile responses to noradrenaline (NA), clonidine and to electrical field stimulation (FS), was studied in the rat isolated seminal vesicle. The aim was to analyse the mechanism of action of DMI in this preparation and compare the results obtained with those already published for other similar preparations, e.g. the guinea-pig seminal vesicle. The results showed that DMI, which on its own had little effect on contractility of rat seminal vesicle, significantly (P less than 0.001) enhanced the Na-induced contractions (by 30-50%), whereas it markedly reduced (by 40%) the contractions produced by clonidine. DMI also enhanced the FS-induced contractions (by about 50%) in the same preparation. The enhancement of the NA-induced responses by DMI can be explained in terms of inhibition of the NA uptake by the preparation, whereas the reduction in clonidine response may be due to blockade of adrenoceptors in the rat seminal vesicle. Other possibilities and mechanisms are also discussed in this and other types of smooth muscle preparations. PMID- 2330343 TI - Sauvagine: effects on thermoregulation in the rat. AB - Sauvagine is a 40 amino acid peptide, isolated from the skin of the South American frog, Phyllomedusa sauvagei, and structurally related to mammalian corticotropin releasing factor (CRF). Experiments with centrally or peripherally injected sauvagine produced dose-dependent hypothermia in rats kept at ambient temperatures of +4 degrees C and +22 degrees C, but no effect was seen on rats maintained at +34 degrees C. To determine whether a pituitary-adrenal dependent step was involved, the thermoregulatory response was studied in hypophysectomized, adrenalectomized and sham-operated rats maintained at a room temperature of +22 degrees C. Significant hypothermia was produced in all three experimental groups, showing that this response is not mediate by the pituitary adrenal axis. CRF had no effect on the thermoregulatory functions of rats and furthermore alpha-helical CRF (9-41), a CRF receptor antagonist, which inhibited the pituitary and cardiovascular actions of sauvagine, did not modify the thermoregulatory response in rats. PMID- 2330344 TI - Blood kinetics of sulfamonomethoxine and oxytetracycline following intrauterine spray injection in dairy cows. AB - Intrauterine administration was performed in six Friesan cows with a disposable spray preparation containing 3 g of sulfamonomethoxine and 3 g of oxytetracycline, in order to investigate their serum kinetics. Sulfamonomethoxine levels were determined by a reversed-phase HPLC method, whilst oxytetracycline quantities were detected by a microbiological method. The sulphonamide had a peak 1.17 h after the administration, the tetracycline reached its highest concentration after 8 h. The bioavailability of both drugs was low and detectable drug amounts were no longer recovered after 24 h. PMID- 2330346 TI - [Retroperitoneal hemorrhage in an autopsy sample: incidence and causes]. PMID- 2330345 TI - Effect of plasma from cancer patients on rat skeletal muscle protein degradation and PGE2 release in vitro. AB - Cachexia in tumour-bearing patients involves loss of skeletal muscle proteins. In order to elucidate the mechanisms underlying this phenomenon, we tested the hypothesis of the presence of a circulating proteolytic factor (possibly interleukin-1, acting through an increased PGE2 release) in the plasma of cancer patients, because such a mechanism has been demonstrated in patients with sepsis or trauma and in animals with bacteraemia or viraemia. The effect of plasma from 13 malnourished cancer patients and 14 controls on PGE2 release and protein degradation (assessed as Tyr release) in rat diaphragm in vitro was evaluated; human recombinant interleukin-1 alpha (IL-1) was used for comparison. IL-1 increased PGE2 release (+44% at 5 U/ml), but did not greatly affect proteolysis. On the contrary, human plasma (125 microliters/ml) from both control and tumour bearing individuals did not affect PGE2 release significantly, but greatly reduced Tyr release. The decrease in Tyr release by plasma was dose-dependent. In conclusion, our data indicate that, at variance with what was demonstrated in patients with trauma or sepsis, loss of skeletal muscle proteins in cancer patients is not mediated by a circulating factor. In addition, evidence is provided of dissociation between PGE2 and Tyr release and of lack of proteolytic activity for IL-1. PMID- 2330347 TI - [Experiences with the electronic data processing system "Teamdata" in pathology]. PMID- 2330349 TI - [New aspects of TNM consultation by the German Language Committee]. PMID- 2330348 TI - [Multiple adenomas of both kidneys--"renal adenomatosis?"]. PMID- 2330350 TI - [Legal evaluation of an autopsy clause for hospital circumstances, which provides conflict resolution. A decision by the Koblenz Federal Court, 15 September 1989]. PMID- 2330351 TI - [Primary ciliary dyskinesia syndrome. Ultrastructural observations in a pair of twins]. PMID- 2330352 TI - [Chronic ischemic gastropathy--a clinicopathologic entity?]. PMID- 2330353 TI - [Spindle cell hemangioendothelioma--a low grade malignant angiosarcoma]. PMID- 2330354 TI - [Leishmaniasis of the upper gastrointestinal tract in an HIV positive patient]. PMID- 2330355 TI - [The mechanisms of a decreased tolerance for graduated physical loading in young patients suffering from diabetes mellitus]. AB - A study of graded exercise tolerance (GET), indices of central hemodynamics and energy metabolism in 136 patients with insulin-dependent diabetes mellitus and 35 controls aged 16 to 40 has shown reduced GET in 86% of the patients. It was combined with a decrease in the CVS functional potentialities and disorder of energy formation. The lowest level of GET was noted in patients with a severe type of diabetes mellitus in marked decompensation, with disease of 10 yrs. of duration at advanced stages of diabetic microangiopathies. The use of inosine and AMP is accompanied by a rise of GET and the activity of energy producing systems. PMID- 2330356 TI - [C-peptide, diabetogenic factor and the blood anticoagulating system in patients with the insulin-dependent type of diabetes mellitus before and after heparin therapy]. AB - The authors analyzed the results of investigation of insulin residual secretion determined by the concentration of C-peptide in response to the stimulation of 1 mg of glucagon. The blood level of the diabetogenic factor (DGF) and activity of the anticoagulative system (ACS) were studied in parallel in patients with insulin-dependent type of diabetes mellitus before and after heparin therapy. The blood DGF disappeared, ACS function was restored, and the patient's body resistance to blood hypercoagulation developed against a background of heparin therapy. A decrease in insulin residual secretion was shown to be related to a duration of diabetes mellitus. PMID- 2330357 TI - [A combination of thyroid diseases with a neoplastic process in the thyroid tissue]. AB - Altogether 252 case records of patients operated on for thyroid cancer were analyzed to determine the frequency of combination of a neoplastic process with autoimmune thyroiditis. Analysis of morphological findings of the operative material has shown that thyroid cancer in autoimmune thyroiditis occurs 2.5-times less than in adenomatous goiter and 1.5-times less in diffuse toxic goiter. The resultant conclusion is that the combination of thyroid cancer with autoimmune thyroiditis occurs more seldom than cancer with diffuse toxic goiter and adenomatous goiter, and the combination of autoimmune thyroiditis with diffuse toxic goiter and adenomatous goiter occurs more frequently than that with thyroid cancer. PMID- 2330358 TI - [Antigens of the HLA system in different types of diabetes mellitus]. AB - HLA antigens (A, B, DR) of the tissues of 171 patients with different types of diabetes mellitus were investigated. Controls were 1867 healthy Leningrad residents (control I), not investigated with the GTT, and 38 pregnant women with the unchanged GTT during pregnancy (control II). Some features of the frequency of occurrence of individual antigens and their interlocular (HLA A, B) combinations in type I and type II diabetes mellitus and diabetes of pregnant women were established. The risk of diabetes mellitus, type I, development was shown to be on the increase in the presence of HLA DR4 in the phenotype and considerably on the decrease in the presence of HLA B17. The results point out to the genetic heterogeneity of different types of diabetes mellitus. The authors think it possible to use HLA typing for the diagnosis of type I diabetes mellitus. PMID- 2330359 TI - [Lipid peroxidation in patients with chronic adrenal cortex failure]. AB - The investigation of 55 patients with chronic adrenocortical insufficiency has shown an increase in the intensity of lipid peroxidation against a background of blood plasma alpha-tocopherol (the main endogenous antioxidant) concentration. The use of vitamin E in multimodality treatment together with substitution hormone therapy resulted in the normalization of indices of lipid peroxidation and antioxidant system necessitating the incorporation of the drug in therapeutic measures in chronic adrenocortical insufficiency. PMID- 2330360 TI - [The functional links in the neuroendocrine interrelationship in juvenile uterine hemorrhages]. AB - A simultaneous and combined study of function of the neuroendocrine regulation of menstrual function in patients with juvenile uterine bleeding (JUB) (by the excretion of LH, noradrenalin, dopa and dopamine with urine and by the blood levels of TSH, T3, T4, ACTH and cortisol and by functional diagnostic tests) has shown that JUB is characterized by dysfunction of all important factors in this complex neuro-regulatory chain, resulting in disorder of hormonal homeostasis and pathological changes in the actuating organs. These changes are particularly marked and profound in JUB developing against a background of irregular menstrual function. PMID- 2330361 TI - [The dependence of estradiol and progesterone reception in the endometrium on its histological structure in women with the syndrome of luteal phase failure]. AB - A study of the level of the sex steroid receptors in the endometrium of women with the syndrome of insufficiency of the luteal phase of the cycle (ILP syndrome) has shown that disorders of receptor processes affect, first of all, progesterone receptors. An increase in a degree of a delay of endometrial development was accompanied by a rise of the level of progesterone in the endometrium which depended on the estradiol-progesterone ratio in the circulation, detectable on the 20th day of the menstrual cycle. The ILP-syndrome is characterized by the sufficient induction of progesterone receptors at the end of the proliferative--the beginning of the luteal phase of the cycle and by their insufficient inhibition with a low level of progesterone in the middle of the luteal phase. Insufficient synthesis of receptors as a result of sharp hypoestrogenemia is less frequent. The primary affection of the receptor apparatus as a cause of the ILP-syndrome against a normal hormonal background in the examinees was undetectable. PMID- 2330362 TI - [A note on the methodological recommendations in endocrinology approved by the Ministry of Public Health of the USSR]. PMID- 2330363 TI - [The mechanism of action of hydrocortisone and adrenaline on the hepatic lysosomal apparatus]. AB - The mechanisms of hydrocortisone and adrenalin action on the structure and function of the lysosomal-vacuolar cell apparatus were studied in experiments on liver sections of Wistar rats. The sections were incubated in Krebs-Ringer bicarbonate buffer, pH 7.4 (95% O2 and 5% CO2) at 37 degrees C for 2 h. Hydrocortisone (10(-5) M) and adrenalin (10(-4) M), added to an incubation medium, were shown to produce a labilizing effect on lysosomal membranes, increasing free activity of acid phosphatase and cathepsin D and osmotic sensitivity of lysosomes. alpha-adrenergic blocker dihydroergotamine (3.4 x 10( 5) M) blocked an increase in free activity of acid phosphatase as a result of adrenalin action but did not eliminate hydrocortisone labilizing action. beta adrenergic blocker propranolol (3 x 10(-4) M) lowered free activity indices and osmotic sensitivity of lysosomes to control values both in the presence of adrenalin and hydrocortisone. The labilization of lysosomal membranes in liver sections was also observed after adding dibutyril-cAMP (10(-8) M) or monobutyril cGMP (10(-13)-10(-9) M) into the incubation medium. PMID- 2330364 TI - [Cellular immunity in patients with insulin-dependent diabetes mellitus studied using the leukocyte migration inhibition reaction]. AB - Disorder of the humoral and cellular immunity is of great importance in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). In 102 IDDM patients the leukocyte migration inhibition test (LMIT) with antigens from the tissue of the endocrine glands was used, permitting the detection of disorder of organ specific cellular autoimmunity. The sensitization of lymphocytes to antigen from the pancreatic islet tissue was detected in 40.2%, to porcine insulin in 22.5%, to thyroid antigen in 16.7%, to adrenal antigen in 9.8%. Leukocyte migration inhibition to the latter two antigens in IDDM patients can serve as an early diagnostic criterion of thyroid and adrenal autoimmune lesion. HLA B8 and B18 occurred more frequently in patients with the positive LMIT, but the differences were insignificant (p greater than 0.1), HLA B15 (p less than 0.02) occurred much less frequently. PMID- 2330365 TI - [The teaching of diabetic patients--an equally valuable component part of their combined treatment (on-the-job training at the WHO center for teaching and treating diabetics)]. PMID- 2330366 TI - Construction of validated, non-redundant composite protein sequence databases. AB - A strategy has been developed for the construction of a validated, comprehensive composite protein sequence database. Entries are amalgamated from primary source data bases by a largely automated set of processes in which redundant and trivially different entries are eliminated. A modular approach has been adopted to allow scientific judgement to be used at each stage of database processing and amalgamation. Source databases are assigned a priority depending on the quality of sequence validation and commenting. Rejection of entries from the lower priority database, in each pairwise comparison of databases, is carried out according to optionally defined redundancy criteria based on sequence segment mismatches. Efficient algorithms for this methodology are embodied in the COMPO software system. COMPO has been applied for over 2 years in construction and regular updating of the OWL composite protein sequence database from the source databases NBRF-PIR, SWISS-PROT, a GenBank translation retrieved from the feature tables, NBRF-NEW, NEWAT86, PSD-KYOTO and the sequences contained in the Brookhaven protein structure databank. OWL is part of the ISIS integrated data resource of protein sequence and structure [Akrigg et al. (1988) Nature, 335, 745 746]. The modular nature of the integration process greatly facilitates the frequent updating of OWL following releases of the source databases. The extent of redundancy in these sources is revealed by the comparison process. The advantages of a robust composite database for sequence similarity searching and information retrieval are discussed. PMID- 2330367 TI - Random mutagenesis used to probe the structure and function of Bacillus stearothermophilus alpha-amylase. AB - Mutations that cover the sequence of Bacillus stearothermophilus alpha-amylase were produced by an efficient in vitro enzymatic random mutagenesis method and the mutant alpha-amylases were expressed in Escherichia coli, which also secreted the product. Ninety-eight mutants were identified by sequencing and their enzyme activities were classified into three classes: wild-type, reduced or null. A molecular model of the enzyme was constructed using the coordinates of Takaamylase A and a consensus alignment of mammalian, plant, and bacterial alpha amylases. The location of mutant amino acids on the model indicate that mutations which destroy or decrease the catalytic activity are particularly clustered: (i) around the active site and along the substrate-binding groove and (ii) in the interface between the central alpha/beta barrel and the C-terminal domain. Exposed loops are typically tolerant towards mutations. PMID- 2330368 TI - Protein-drug interactions: characterization of inhibitor binding in complexes of DHFR with trimethoprim and related derivatives. AB - Structural and thermodynamic interactions for the binding of trimethoprim and related congeners to the binary complex of dihydrofolate reductase (from chicken) and NADPH are explored using free energy simulation methods. Good agreement between structures from experimental X-ray refinement and molecular dynamics simulations is found for the complexes. Agreement with thermodynamic measurements is found as well. Our thermodynamic calculations suggest that entropic contributions and desolvation thermodynamics can play a crucial role in overall binding, and that extreme care must be taken in the use of simple model building to rationalize or predict protein-drug binding. PMID- 2330369 TI - Apolar peptide models for conformational heterogeneity, hydration, and packing of polypeptide helices: crystal structure of hepta- and octapeptides containing alpha-aminoisobutyric acid. AB - The crystal structures of two helical peptides Boc-Val-Ala-Leu-Aib-Val-ala-Leu OMe (VALU-7) and Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe (VALU-8) have been determined to a resolution of 1.0 and 0.9 A, respectively. Both the seven and eight residue peptides crystallize with two conformers per asymmetric unit. The VALU-8 conformers are completely helical and differ only at the C-terminus by a sign reversal of the phi, psi angles of the last residue. One of the VALU-7 conformers occurs as a normal alpha-helix, whereas in the other, the N(7)--O(3) alpha-type hydrogen bond is ruptured by the entry of a water molecule (W) into the helix, which in turn makes hydrogen bonds N(7)...W = 2.97 A and W...O(3) = 2.77 A. The other side of the water molecule is surrounded by a hydrophobic pocket. These two conformers give a static representation of a step in a possible helix unwinding or folding process. In the VALU-8 crystal the helices aggregate in a parallel mode, whereas the aggregation is anti-parallel in the VALU-7 crystal. The crystal parameters are VALU-7, P2(1), a = 10.203 (3) A, b = 19.744 (6) A, c = 22.561 (6) A, beta = 96.76 degrees, Z = 4, C38H69N7O10.0.5H2O, R = 6.65% for 3674 reflections observed greater than 3 sigma (F); and VALU-8, P2(1), a = 10.593 (4) A, b = 27.57 (6) A, c = 17.745 (5) A, beta = 95.76 (3) degrees, Z = 4, C42H76N8O11.0.25 CH3OH, R = 6.63% for 4701 reflections observed greater than 3 sigma (F). PMID- 2330370 TI - Structure determination and refinement of Bacillus stearothermophilus lactate dehydrogenase. AB - Structures have been determined of Bacillus stearothermophilus "apo" and holo lactate dehydrogenase. The holo-enzyme had been co-crystallized with the activator fructose 1,6-bisphosphate. The "apo" lactate dehydrogenase structure was solved by use of the known apo-M4 dogfish lactate dehydrogenase molecule as a starting model. Phases were refined and extended from 4 A to 3 A resolution by means of the noncrystallographic molecular 222 symmetry. The R-factor was reduced to 28.7%, using 2.8 A resolution data, in a restrained least-squares refinement in which the molecular symmetry was imposed as a constraint. A low occupancy of coenzyme was found in each of the four subunits of the "apo"-enzyme. Further refinement proceeded with the isomorphous holo-enzyme from Bacillus stearothermophilus. After removing the noncrystallographic constraints, the R factor dropped from 30.3% to a final value of 26.0% with a 0.019 A and 1.7 degrees r.m.s. deviation from idealized bond lengths and angles, respectively. Two sulfate ions per subunit were included in the final model of the "apo"-form- one at the substrate binding site and one close to the molecular P-axis near the location of the fructose 1,6-bisphosphate activator. The final model of the holo enzyme incorporated two sulfate ions per subunit, one at the substrate binding site and another close to the R-axis. One nicotinamide adenine dinucleotide coenzyme molecule per subunit and two fructose 1,6-bisphosphate molecules per tetramer were also included. The phosphate positions of fructose 1,6-bisphosphate are close to the sulfate ion near the P-axis in the "apo" model. This structure represents the first reported refined model of an allosteric activated lactate dehydrogenase. The structure of the activated holo-enzyme showed far greater similarity to the ternary complex of dogfish M4 lactate dehydrogenase with nicotinamide adenine dinucleotide and oxamate than to apo-M4 dogfish lactate dehydrogenase. The conformations of nicotinamide adenine dinucleotide and fructose 1,6-bisphosphate were also analyzed. PMID- 2330372 TI - An increasing role in education. PMID- 2330373 TI - Making the team work!... AB - Setting up a multidisciplinary team is not simply a question of calling a group of people a team. It must be properly organised for the individual service--once it is decided the team is needed. PMID- 2330371 TI - Computer analysis of mutations that affect antibody specificity. AB - The mouse hybridoma cell line 40-150 secretes antibodies with high affinity toward the cardiac glycosides digoxin and digitoxin. A spontaneous mutant, 40-150 A2.4, produces an antibody which carries a single residue mutation, Ser----Arg, in its heavy chain (H94) and has an altered specificity. A second-order mutant, 40-150 A2.4 P.10, produces two antibody molecules, one the same as 40-150 A2.4, the other lacking two residues at the N-terminus of its H chain, and having a specificity profile approaching that of 40-150 antibody. The N-terminus and the position H94 are distant from the antigen-binding site of the antibody; thus, the structural basis of the specificity changes was not immediately clear. Approximate structures of the 40-150 antibody and its mutants were constructed in the computer, based on atomic coordinates of the homologous mouse antibody McPC 603. Using the program CONGEN, the torsional space of the polypeptide backbone and side chains around position H94 was uniformly sampled, and the lowest energy conformations were analyzed in detail. The results indicate that when Arg-H94 is substituted for Ser, Arg-H94 can hydrogen bond to side chains of Asp-H101, Arg L46, and Asp-L55. This results in a change in the surface of the combining site which may account for the affinity changes. Deletion of the two N-terminal residues increases solvent accessibility of Arg-H94. The solvation may cause a hydrogen bond between Arg-H94 and Asp-H101 to be lost, restoring the structure to one similar to that of 40-150. PMID- 2330374 TI - An extra source of conflict? Diabetes in adolescence. AB - Adolescence can be difficult at the best of times, but being diabetic can add extra stress. Nurses can minimise this by supporting diabetic adolescents and helping them lead as normal lives as possible. PMID- 2330375 TI - When the brain is the target: support in neurological manifestations of HIV/AIDS. AB - Many people with Aids develop a range of neurological manifestations, which can cause great distress to them and their loved ones. Nurses are ideally placed to offer both practical and psychological support--if it is required. PMID- 2330376 TI - A logical approach. Management of surgical wounds. AB - The main concern in managing surgical wounds is preventing infection. Nurses need to be able to interpret research on the subject and adapt their practice accordingly. PMID- 2330377 TI - A new image to accept: psychological aspects of stoma care. AB - Patients undergoing ileostomy or colostomy surgery face permanent changes to their accepted body image and lifestyle. This article examines the conscious and subconscious reactions patients exhibit in response to this. PMID- 2330378 TI - Dilemmas in neonatal units. AB - The second article in our series on SCBU identifies the ethical dilemmas underlying work in neonatal units, and which make it so emotional and demanding. PMID- 2330379 TI - Breaking the cycle--control of breathlessness in chronic lung disease. AB - The attacks of breathlessness experienced by patients with chronic lung disease set up a frightening cycle of lack of exercise and worsening lung function unless patients take control of their condition. Nurses can help them. PMID- 2330380 TI - That personal touch we must not lose. PMID- 2330381 TI - Molecular and cellular regulation of calcium and phosphate metabolism. Proceedings of a symposium. Vienna, November 17, 1988. PMID- 2330382 TI - Thyroid hormone enhances the genomic action of calcitriol in the small intestine. PMID- 2330383 TI - [Synthesis and biochemical properties of new 10-acyl derivatives of dithranols: acetylsalicyldithranol and 1-acetyllactyldithranol]. AB - By reaction of the corresponding acid chlorides of acetylsalicylic acid (8) and L acetyllactic acid (5) with dithranol (1) in toluene and collidin or pyridine as a base two new 10-acylderivatives of (1) were prepared: L-acetyllactyldithranol (2) and acetylsalicyldithranol (3). Both derivatives strongly inhibited the enzyme glucose-6-phosphate dehydrogenase, indicating possible antipsoriatic activity. PMID- 2330384 TI - Relaxation response to pinacidil and diazoxide in the mouse isolated distal colon. AB - Pinacidil and diazoxide induced concentration-related relaxations of the longitudinal muscle of the mouse distal colon. The relaxing effects of pinacidil and diazoxide were unaffected by tetraethylammonium, but were antagonized by tolbutamide and glibenclamide. Relaxations provoked by nifedipine were not counteracted by the two hypoglycaemic sulfonylureas. It is tempting to suggest that the relaxation response to pinacidil and diazoxide could reflect the ability of both compounds to interfere with membrane K+ channels sharing common pharmacological properties with the K+ATP channels recently described in other tissues. PMID- 2330385 TI - Influence of long-term treatment of the rat with clebopride on the morphology of the mammary gland. AB - The substituted benzamides or orthopramides are used to treat gastrointestinal and psychotic disorders. The orthopramide clebopride, a potent dopaminergic antagonist, blocks emesis in dogs and stereotyped behavior in rodents. Since the release of prolactin is inhibited by dopamine, antidopaminergic drugs may be useful to increase lactation in nursing mothers. The present work examines the morphological and histological alterations produced by long-term treatment of puerperal and virgin female rats with clebopride. Clebopride induced significant hyperplasia of parenchymal secretory units and stimulated milk secretion in both groups of rats. However, only in virgin rats was mammary weight significantly increased. PMID- 2330386 TI - [Psychology in medicine--psychology as medicine]. PMID- 2330387 TI - Peripheral catecholamine levels and the symptoms of anxiety: studies in patients with and without pheochromocytoma. AB - We studied the correlation of plasma and urinary epinephrine (E) and norepinephrine (NE) levels with anxiety symptoms in three patient groups: 1) pheochromocytoma (PH+) (n = 17); 2) hypertensives with elevated catecholamine levels shown not to have a PH (PH-) (n = 25); and 3) patients with panic disorder (PD) (n = 23). Structured interviews and four self-rated anxiety scales were used: the SCL-90R Anxiety and Phobic Anxiety scales, and the Spielberger State/Trait Anxiety Inventories. The SCL-90R Somatization scale (which measures 12 somatic symptoms) was also utilized. None of the PH+ patients met DSM-III criteria for PD. Two met criteria for generalized anxiety disorder (GAD). Of the PH- patients, two had PD, two had GAD, and three had both. Urinary and plasma E did not show significant positive correlations with any of the four anxiety scales in any of the three patient groups. In both the PH+ and PH- groups, E was significantly correlated with the SCL-90R Somatization scale. NE was not significantly correlated with any of the four anxiety scales in the PH+ group. In contrast, in the PH- group, plasma NE was significantly correlated with anxiety on all anxiety scales (r = +0.55 to +0.77, p less than 0.05). Furthermore, in the PH- group, plasma NE was significantly correlated with those items of the SCL-90R Anxiety scale measuring the cognitive rather than the noncognitive symptoms of anxiety. In the PD group as well, plasma NE showed a significant correlation with the SCL-90R Anxiety Scale (r = +0.67, p less than 0.05). Taken together, our observations suggest that: 1) the effects of catecholamines in the periphery derived from a source independent of nervous system control (such as a PH) are not sufficient to elicit an anxiety disorder meeting DSM-III criteria; and 2) in patients without an autonomous source of peripheral catecholamines, NE in the periphery results from sympathetic nervous system activation and probably reflects, rather than causes, anxiety. PMID- 2330388 TI - Self-schema in irritable bowel syndrome and depression. AB - Some investigators have suggested that irritable bowel syndrome (IBS) represents a physiologic expression of an affective disorder. This study investigated whether IBS patients differed in their self-schema from depressed patients. Self schema refers to a cognitive framework of the individual's beliefs, attitudes, and self-perceptions which is stored in memory and which influences incoming information. The sample consisted of 21 IBS patients, 21 psychiatric outpatients with major depression (MD), and 19 normal controls. All groups were age matched. Subjects completed a structured psychiatric interview (Diagnostic Interview Schedule (DIS) and a Beck Depression Inventory (BDI), in addition to a test of self-schema, which involved rating and recall of a variety of "depressed" and "nondepressed" content adjectives. Consistent with previous work on self-schema, the MD group recalled significantly more depressed adjectives rated under the self-referent task than the Control group (p less than 0.05) and, also, the IBS group (p less than 0.05). Most striking was the finding that a subgroup of IBS patients who met criteria for MD (43% of the sample) recalled significantly more self-referent nondepressed words (and less self-referent depressed words) than the MD group (p less than 0.05). In other words, IBS patients with MD do not view themselves as depressed. These findings suggest that while some IBS and depressed psychiatric outpatients may share depressive symptoms, these groups can be differentiated by their self-schema. PMID- 2330389 TI - Personality features of women with good outcome from restricting anorexia nervosa. AB - Personality characteristics were assessed in women who had physically and, in the majority, psychologically recovered from restricting anorexia nervosa at an 8- to 10-year follow-up. Personality dimensions were evaluated using the Multidimensional Personality Questionnaire, the California Personality Inventory, and the Reid-Ware Scale. Women who had recovered from anorexia nervosa rated higher on risk avoidance, displayed greater restraint in emotional expression and initiative, and showed greater conformance to authority than age-matched normal women. On comparison with their sisters, the recovered women reported a greater degree of self- and impulse control and less enterprise and spontaneity; sisters, however, endorsed equally high moral standards. The differences in personality characteristics remained significant after statistically controlling for depressive symptoms and eating behavior. The results suggest that a temperamental disposition toward emotional and behavioral restraint combined with a strong sense for traditional values may be psychological risk factors for the development of the restricting type of anorexia nervosa. PMID- 2330390 TI - Ethnographic assessment of pain coping perceptions. AB - A sample consisting of 54 patients and 31 dentists of Chinese, Anglo-American, and Scandinavian ethnic origin were interviewed about their ways of coping with pain. Instruments designed to assess pain coping were constructed from the descriptions elicited by the interviews. The interview data thus served as the basis for cross-cultural quantitative indices. Content analysis of the interviews revealed significant differences between patients and dentists and an East-West ethnic difference between patient groups. Anglo-American patients and all dentists preferred internally applied medicines (pills, injections etc.). Chinese patients preferred external agents (salves, oils, massage, etc.) significantly more than Chinese dentists or Western subjects. Swedish and Chinese patients preferred not to use local anesthesia for dental treatment. These results were corroborated by nonparametric and multidimensional scaling analyses of the cross cultural quantitative data. Professional socialization had a stronger influence on pain remedy description than did ethnicity, while patient descriptions of remedies appeared to be more ethnospecific, especially showing East-West differences. These anthropologic methods appeared to be valid and reliable in revealing cognitive processes involved in the pain coping preferences of these subjects. PMID- 2330391 TI - Lifestyle, stress, and blood pressure in a southern black community. AB - The effects of lifestyle incongruity on blood pressure were examined in research in an African-American community in the southern United States. Lifestyle incongruity is defined as the extent to which a high status style of life (based on possession of material goods and exposure to mass media) exceeds an individual's occupational class. In a sample of 186 25- to 55-year-olds, higher arterial blood pressure was related to higher lifestyle incongruity, especially among persons aged 40-55. These effects were independent of perceived chronic social role stressors, a self-report diagnosis of hypertension, age, sex, body mass, and skin color. Future research should examine more closely those social and psychological factors that might moderate the risk associated with lifestyle incongruity. PMID- 2330392 TI - The expression and perception of facial emotion in alexithymia: a pilot study. AB - The term alexithymia denotes a cluster of traits including a marked difficulty in finding words to describe emotions. Despite a rapidly growing literature, the construct has not been validated adequately. The present study addressed the validity of the construct. Twenty males assessed as alexithymic or not, on the basis of the Schalling-Sifneos Personality Scale, were videotaped during tasks designed to elicit spontaneous and posed facial expressions of emotion. They also rated the emotional impact of the tasks and prototypic displays of emotion. Results showed that alexithymics were comparable to controls in judgments of the impact of provocative slides and in their ability to label posed expressions. With the exception of expressions of anger and happiness, they were also comparable in the ability to pose emotions. Alexithymics showed a deficit in spontaneous displays of negative affect. Results support the validity of the concept and suggest that deficits in nonverbal expression are central to the phenomenon. Implications for conceptualizations of alexithymia and emotion are discussed. PMID- 2330393 TI - Abstracts of papers. Annual meeting of the American Psychosomatic Society. March 22-24, 1990, Boston. PMID- 2330394 TI - Effects of acute increases in altitude on mental status: prevention and treatment. AB - Healthy individuals may develop mental status changes and somatic symptoms, known as acute altitude (or mountain) sickness, when rapidly ascending to higher altitudes. Patients with cardiopulmonary and neurologic problems and elderly individuals are at an increased risk for developing these symptoms. This article describes the symptomatology and risk factors for the condition and presents four case examples. Preventive and treatment measures are recommended. PMID- 2330395 TI - The changing faces of somatization. AB - The prevalence of several diseases popularized by the media is examined in a group of 50 consecutive patients allegedly suffering from environmental hypersensitivity disorder. Ninety percent of patients reported suffering from at least one other "fashionable" condition, including food allergies that cause psychological symptoms, postinfectious neuromyasthenia, candidiasis hypersensitivity, and severe premenstrual syndrome. Each of the conditions named above was endorsed by at least 50% of patients. Multiple endorsements were common, and the patients' attribution of the etiology of their symptoms varied with time. Physicians must become adept at identifying and managing somatizing patients, and the public must be educated about somatization and provided with reliable information about "fashionable" illnesses. PMID- 2330396 TI - Longitudinal change in HIV transmission risk behaviors by gay male physicians. AB - Gay male physicians were surveyed in 1984 and 1985 about their knowledge and attitudes regarding HIV transmission and AIDS and changes they had made in social, health-related, and sexual activities since the onset of the AIDS epidemic. Most of the 37 subjects who participated in both surveys progressively lessened their participation in HIV transmission risk behaviors over time. Health belief, AIDS knowledge, health coping, social support, mood state, and age factors all contributed to changes in sexual behavior. The modeling of sexual behavior changes showed general stability over time. This study provides further evidence that multiple psychosocial factors are associated with changes in sexual behavior, even in gay male physicians. PMID- 2330397 TI - Panic disorder in cardiac outpatients. AB - The prevalence of and nature of panic disorder were investigated in an ambulatory cardiology practice. Questionnaires about panic symptoms were mailed to 414 patients, and possible or definite panic disorder was found in 104 of the 310 respondents. Interviews with 52 of the 104 patients substantiated diagnoses of panic disorder, for a prevalence of 9.2% of the total sample population of 414. Comparison of patients grouped by duration of panic disorder revealed that long duration panic disorder had its onset before age 30 and followed a chronic course. Short-duration panic disorder developed at an older age following the appearance of cardiac disease. PMID- 2330398 TI - Symptomatology of late-life minor depression among primary care patients. AB - Patients of four general internists and four family physicians were interviewed by two psychiatrists to identify those suffering from depressive disorders. Nineteen elderly (60 years of age and older) patients and 22 younger (between 18 and 59 years of age) patients met Research Diagnostic Criteria (RDC) for minor depressive disorder, and 73 elderly and 79 younger patients had no psychiatric disorder. In general, the elderly depressed medical outpatients and the younger depressed medical outpatients had similar symptomatology, as did the elderly and nonelderly medical outpatients without psychiatric disorders. PMID- 2330399 TI - Psychiatric syncope: a new look at an old disease. AB - Psychiatric disorders in patients with unexplained syncope or presyncope have received little attention in the recent medical literature. Seventy-two patients with unexplained syncope and presyncope referred to the Duke Syncope Clinic received a standardized evaluation. Symptoms appeared to be explained by a psychiatric diagnosis in 17 (24%) patients (panic disorder in 13%, and major depression in 11%). These patients were younger than other patients with syncope and presyncope (p less than .001) and had more disability due to their syncope and presyncope (p less than .01). They also had more frequent episodes of syncope (p less than .005) and more symptoms as a part of their prodrome (p less than .0001). Treatment aimed at the psychiatric diagnosis resulted in a remission from syncopal or presyncopal symptoms in 90% of patients who complied with therapy. The authors conclude that psychiatric disorders are common in patients with syncope and presyncope, that certain characteristics of the patient and prodrome may alert physicians to a psychiatric diagnosis, and that directed treatment may result in relief from symptoms. PMID- 2330400 TI - A curriculum in clinical sexuality for arthritis health care professionals. AB - The results of an experimental training program in sexologic interviewing for a multidisciplinary arthritis patient care team are reported. The program included didactic instruction, observation and practice of interviewing skills, a seminar, and a case presentation. Trainees had gained more knowledge than control subjects at one year. Both groups improved their interviewing skills, but trainees showed more improvement than controls on problem-list generation. All participants showed more improvement when interviewing male than female patients. The data show that training programs in sexologic interviewing can improve both knowledge and skills. Programs should include actual practice interviewing patients. PMID- 2330401 TI - An efficient method for psychosocial screening of cancer patients. AB - In high-volume outpatient areas, using Weisman and Worden's Omega instruments for psychosocial screening of cancer patients is not feasible. This study of 30 newly diagnosed patients compared the accuracy of the Omega instruments and the Brief Symptom Inventory (BSI) in identifying patients with high levels of distress at the time of diagnosis as well as in predicting future distress. A significant level of agreement was found between the BSI and the Omega instruments. Both instruments correctly identified the future distress of 16 of 19 patients (84.2%), but the BSI screens patients in one-fourth the time and at one-third the cost. These results support our decision to employ the BSI as a screening tool in an outpatient setting. PMID- 2330402 TI - Posttraumatic stress disorder: somatic comorbidity and effort tolerance. AB - To explore psychological and somatic distress following trauma, the authors compared 50 combat veterans with chronic posttraumatic stress disorder (PTSD) with 48 age-matched combat veterans without PTSD. Both groups were evaluated on symptom reports, physical examination findings, and laboratory tests. Subjects with PTSD reported significantly more symptoms, but they did not differ from controls on their physical examination and laboratory test findings. Adverse health practices (smoking, alcohol use, and deregulation of food intake) were significantly more frequent in the PTSD group. Low effort tolerance, as has been reported in panic disorder patients, was observed in the PTSD group. PMID- 2330403 TI - Frequency of constipation in major depression: relationship to other clinical variables. AB - A semistructured interview that evaluates 70 clinical variables, including constipation, was administered to 170 patients with major depression. Twenty seven percent of the patients had depression-associated constipation. Constipation was not associated with any other clinical variable. PMID- 2330404 TI - The psychotic fear of AIDS. PMID- 2330405 TI - Dysmorphophobia misdiagnosed as obsessive-compulsive disorder. PMID- 2330406 TI - Thyrotoxicosis and bulimia nervosa. PMID- 2330407 TI - Acute laryngeal dystonic reactions. PMID- 2330408 TI - [CT diagnosis of the elbow joint]. AB - The normal anatomy of the elbow joint is described. Diverse pathologic joint alterations, e.g. fractures and dislocations, osteochondritis, inflammatory changes, and ulnar nerve lesion are demonstrated. Particular attention is paid to three-dimensional (3D-) reconstruction of demonstrable pathologic findings. PMID- 2330409 TI - [The search for joint loose bodies in the elbow joint--conventional or CT arthrography?]. AB - Assessment of intraarticular loose bodies in the elbow joint with CT arthrography is more successful than with conventional arthrography. Calcification in the capsule is better delineated by CT. The diagnosis of osteochondrosis dissecans can mostly be established by plane ray and conventional tomography. PMID- 2330410 TI - [A calcified tumor in the mesenterium. Ovarian carcinoma with a calcified metastasis in the abdominal wall ("omental cake"), histologically cystadenocarcinoma]. PMID- 2330411 TI - [Differential diagnosis of distortion of the elbow joint]. AB - Distortion of the elbow joint often means a vague diagnosis describing a traumatized joint with no radiological changes, or it means a transient diagnosis until sophisticated examinations can demonstrate what the injury really is. In adults there are only a few injuries that cannot be shown by radiography. In children, however, radiography of the elbow joint is more difficult due to the inhomogeneity during growth. Contrary to adults, fractures misdiagnosed in radiography often result in significant reduction of joint function. PMID- 2330412 TI - [Functional significance of bent DNA in transcriptional regulation]. PMID- 2330413 TI - [Aberration of macrophage in autoimmune diseases]. PMID- 2330414 TI - [Neural induction in amphibian embryos involves cross-talk of signal pathways of protein kinase C and adenylate cyclase]. PMID- 2330415 TI - Of Lucy, diet, fiber, and white horses... PMID- 2330416 TI - Toxicological evaluation of food additives. Toxicological evaluation over estimation of potential high intake to permitted levels of use of food additives and vice versa. AB - Permitted levels of use for food additives should agree with the acceptable daily intakes (ADIs) established by toxicologists. To ensure accordance, nutritional and physiological factors can be used to estimate high intakes of food and beverages. Appetite and thirst (energy and liquid requirements) are such quantitative factors. They are universal and, if placed on the same level as the ADI, i.e., expressed on a kilogram of body weight basis, can be used to estimate high intakes of an additive. This tool can be easily used to judge whether a suggested level of use may cause consumption of the additive to exceed the ADI. It also tells us to what level (ADI) toxicological clearance should be sought, when the technological need is known. The method is independent of food consumption surveys, but these may be carried out to confirm its forecasts. This paper uses caramel in soft drinks as an example. The approach, also called "the budget method," has been tried out in Denmark and Sweden. It is now being offered as a solution to the problem facing the European Communities: to establish before 1993 a common list of food additives containing quantitative limitations for use. PMID- 2330417 TI - Guidelines for the definition of environmental action alert thresholds for polychlorodibenzodioxins and polychlorodibenzofurans. AB - In July 1986, a 314-ha area surrounding the municipal solid waste incinerator of San Donnino (Florence, Italy) was subjected to hygienic and sanitary measures as polychlorodibenzodioxins (PCDDs) and polychlorodibenzofurans (PCDFs) had been detected in soil at levels higher than the "reference technical limits" adopted by the National Toxicology Commission in 1985. In this report the case of San Donnino is the starting point used to define "maximum tolerable environmental limits" for complex mixtures of PCDDs and PCDFs. Limits are expressed in "2,3,7,8 tetrachlorodibenzo-p-dioxin toxicity equivalence" units according to a relative toxicity ranking where the toxic potency of the aforementioned chemical is considered the highest and set equal to unit. Man's exposure to PCDDs and PCDFs is estimated on the basis of experimental findings and with reference to such limits. PMID- 2330418 TI - [Flow in the umbilical cord in normal and high-risk pregnancies]. AB - The author studied umbilical venous blood flow in 100 normal pregnant women and in 100 pregnant women with apparent delay in intrauterine growth (DIUG). At birth, it was shown that only 50 babies had DIUG and that the blood flow was low in 49. In the other 50 babies there was no DIUG and blood flow in the umbilical vein was normal in all of them. The same study was carried out in 50 pregnant women with fetal hypoxia due to placental pathology (32), hemorrhage in the third trimester (15) and Rh isoimmunization (3). This study showed that increased blood flow in the umbilical vein is an early and sure sign of hypoxia due to placental pathology, hemorrhage in the last three months of gestation or Rh isoimmunization. It was also ascertained that low umbilical venous blood flow is a bad prognostic sign because it indicates that the fetus receives an abnormally low quantity of originated blood from the placenta, as was the case of the fetus with DIUG or in the final stages of hypoxia, and that when this happens, the fetus is already incapable of controlling the compensatory circulatory mechanisms and is at imminent risk of cardiac damage. PMID- 2330419 TI - [Population pharmacology and ethnopharmacokinetics in 3 Amerindian groups from Panama: Cuna, Ngawbe Guaymi and Teribe]. AB - We report on studies of the oxidative routes associated with the polymorphic metabolism of debrisoquine, sparteine and mephenytoin, as well as on the pathway catalyzed by N-acetyl-transferase. Normal, healthy non-related subjects were studied: 250 Cuna, 285 Ngawbe Guaymi and 20 Teribe. These studies were aimed at establishing differences or similarities among Amerindian tribes and between them and Caucasians, since certain abnormal or non-expected results in clinical response to drugs could be due to racial differences. In those cases, it was considered necessary to evaluate the degree of toxicity and danger of drugs administration, and their effective therapeutic actions. PMID- 2330420 TI - [Cases of ocular mycosis at the metropolitan hospital complex of the Social Security Fund (1979-88)]. AB - Of 277 eye specimens processed during the ten-year period of January, 1979 through December, 1988 in the Social Security Hospital, we isolated fungi 115 times. The fungal isolations were equally distributed between the two sexes, our rainy season months being the most productive with almost 70% of the recoveries. Candida species were identified in 90 (78%) of 115 cultures, C. albicans being the most frequent (46 cultures or 51%) followed by C. parakrusei (19 isolations, 21%). Less frequently obtained organisms were Fusarium (8 times, 7%), Aspergillus (4 cultures) and others, even No cardia brasiliensis in one instance. PMID- 2330421 TI - [Hemorrhoids. Medico-surgical treatment]. AB - The clinical history of 300 patients examined by the author at San Fernando Clinic and 90 consecutive cases operated at CHMCSS were studied. The frequency and characteristics of symptoms, the gender prevalence, the physical findings, the clinical classification and the various therapeutic methods used were determined. It was noticed that 84% of the patients received conservative treatment and 16% were subjected to surgery. The conservative treatment consisted of high fiber diets, warm sits baths, psyllium, hemorrhoidal sclerosis or ligature with rubber bands. The surgical treatment consisted of the ligature and excision of the three primary hemorrhoids and of the hemorrhoidal plexus(5), which is a simple, fast and effective technique, because the removal of the hemorrhoidal cushion avoids recurrences. Furthermore, the suturing of the longitudinal fibers and the pedicle and their fixation to the external sphincter avoids the upward retraction of the pedicle and the formation of denuded areas in the anal canal that can lead to stenosis at the level of the anorectal ring. PMID- 2330422 TI - [Anal hematoma (coagulated venous saccule or peri-anal thrombosis)]. AB - The Author reviews the clinical histories of eighty patients seen in his private practice with the diagnosis of anal hematoma. He discusses the true nature of "anal hematoma" and points out that it is really a clot in one of the venous sacs of the external hemorrhoidal plexus; and comment the symptomatology and the results of therapy. PMID- 2330423 TI - [Acute kidney insufficiency of obstetric origin. Experience at the Santo Tomas Hospital (1966-1981)]. AB - The authors review 24 cases of acute renal failure of obstetric etiology occurred in Hospital Santo Tomas, which represents a frequency of 1.375/10,000, with a bimodal distribution and the main causes were toxemia of pregnancy and sepsis. All cases were of the oliguric type and a kidney biopsy was performed in 17 cases, revealing an acute tubular necrosis in 16 and a diffuse cortical necrosis in the other case. Two patients (8.3%) died and one did not received nephrology treatment as the other 23 patients. The fetal mortality was 37.5% and the Apgar was good in 2, fair in one and bad in 2. A 50% of the complications were infections and nine patients tolerated different surgical procedures after the installation of the acute renal failure. The follow-up of 12 patients shows no evidence of renal failure. PMID- 2330424 TI - [Pathogenesis of the delusional formation in Ekbom's syndrome]. AB - The Authors describe the clinical histories of two patients who presented with the infrequent delusion of being infected with very tiny organisms which crawl in the skin (Ekbom's syndrome) and comments on its phenomenological characteristics and nosological classification. In their discussion they clarify aspects of the pathogenesis of delusions in this condition. PMID- 2330425 TI - [Endoscopic management in biliary problems. 4 years' experience]. AB - We studied the clinical records of 81 patients referred for endoscopic sphincterotomy in the period of June 1985 to December 1989, 54 were females and 27 males. Indication for the procedure were stones in the choledochus in 68 (84%) patients, malignant neoplasm that affected the biliary tree in 9 (11.1%), "sump syndrome" in 2 (2.5%), intrahepatic papillary stenosis and stones in 1 case, respectively. In 13 of the 81 patients the procedure was accompanied by treatment with the use of biliary prosthesis. We used the endoscopic sphincterotomy in 73 of the 81 (90.1%) patients, observing acute complications in 6.2% due to bleeding at the point of tubal insertion, pancreatitis, or acute cholecystitis. In 10 (76%) of 13 patients, in which the biliary prosthesis was used, the procedure was successful; in only one, acute cholangitis. There was no mortality associated with the procedure. PMID- 2330426 TI - [Propedeutic course in the medical school at Panama University in 1989]. AB - An analysis was made of the data necessary to establish a pre-university propaedeutic course in the Faculty of Medicine of the University of Panama, and its qualitative and quantitative evaluation of the results obtained. The necessity to select the students who wished to enroll in the faculty of medicine was demonstrated because of the failing of the student, whichever was due to inclination, aptitude or scientific knowledge. This is in order to avoid that the student incorrectly chooses a course in which he could not successfully study. PMID- 2330427 TI - [The use of shrimp and turkey buzzard flour and milk whey in food for shrimp under controlled laboratory conditions]. AB - Two diets were prepared for the shrimp's development in the tanks, based on fish meals, shrimp's head meals, "gallinaza" and milk whey. The diets had a protein concentration of 37.8% and 45%, using as control a commercial diet with 35% of protein. Twelve juvenile shrimps with average weights of 2.30 gr. to 3.09 gr were used in each of the six-40 liter aquariums under laboratory controlled conditions for a 28 days period. The growth increments were low in spite of the high protein concentration, due to a deficiency in some essential aminoacid and were not successful in supplementing it with the protein sources used. The aquarium areas turned out to be limiting and growth was affected by density. The statistic analysis showed no significant differences in the treatments used. PMID- 2330428 TI - [Unilateral epidural anesthesia]. AB - Four cases of unilateral spread of epidural anesthesia are presented. All were documented by X-ray epidurography. In two patients the catheter had passed immediately into one of the intervertebral foramina so that the local anesthetic had almost totally been injected into the paravertebral space. In the third and fourth cases a membrane was present in the dorsal epidural space that had prevented bilateral spread of the local anesthetic. This article discusses the fact that strands of the dorsomedian connective tissue band of the lumbar epidural space can cause catheters to coil up, be diverted, and not infrequently be directed into the next intervertebral foramen. These strands sometimes form a dense membrane, which together with the plica mediana of the dura mater prevent symmetrical spreading of epidurally injected fluids. When informing a patient about epidural anesthesia, the anesthesiologist should mention that anatomical variations in the epidural space can cause epidural anesthesia to spread unilaterally. PMID- 2330429 TI - [The concentration of free lidocaine in arterial, central venous and peripheral vein plasma following intravenous injection]. AB - Ten intensive care patients and five healthy volunteers each received a bolus injection of lidocaine HCl (100 mg, 2%) over an injection period of 5 s. After 0.5, 1, 2, 4, 8, 15 and 25 min arterial, central venous and peripheral venous blood samples were collected. In four of the volunteers, arterial and central venous samples were also taken about 10 s after the end of injection. The fluorescence polarization method by means of the Abbott-TDx system was used, and plasma concentrations of lidocaine were determined. The measurements showed that lidocaine levels in central venous plasma 10 s after the end of administration were higher than those in arterial plasma. By 30 s after administration the opposite situation had developed, so that arterial concentrations were higher than those in central venous plasma. This relation did not change throughout the study, though the two levels became closer, as is shown by the ratios (Table 3, Fig. 2). Concentrations in peripheral venous plasma increased more slowly but remained far below those in arterial and central venous plasma, at least for the first 8 min. After 15 min lidocaine levels were almost the same in all three samples. During the entire study there were no ECG changes, and neither heart rate nor blood pressure showed any significant deviation from the values obtained at the beginning. The volunteers had minor toxic manifestations, such as dizziness, tinnitus and a metallic taste in the mouth; one person had a sensation of pressure in his chest, which improved following oxygen administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330430 TI - [Complications of the postoperative use of lumbar epidural catheters in place for surgery]. AB - Two cases of secondary subarachnoidal dislocation of lumbar epidural catheters are reported. The first catheter was placed, tested, and injected with 20 ml local anesthetic in order to achieve intraoperative anesthesia up to the T4 level. On the 2nd postoperative day the test dose produced paralysis of the lower extremities; liquor now could be aspirated. The second catheter had been introduced into the epidural space immediately after injection of 15 ml local anesthetic through the needle. Use of this catheter for postoperative analgesia led to total spinal anesthesia in spite of negative aspiration and test dose prior to injection of 7 ml local anesthetic. Implications of these two cases concerning placement procedures and monitoring during reuse of catheters placed some time before are discussed. PMID- 2330431 TI - [Occlusion of an implanted peridural catheter by a plug of epidermis]. AB - A patient suffering from intensive perianal pain due to recurrent rectal cancer, not controllable by systemic analgesics, was treated by continuous epidural morphine for a period of 8 months. Satisfactory pain relief was achieved although sometimes problems arose with the permeability of the epidural catheter. As a reason for increased resistance, the literature mentions nonspecific foreign-body reactions next to the catheter. In our patient, tumour infiltration into both the lumbosacral plexus and the epidural space leading to compression of the catheter could not positively be excluded. At autopsy an unexpected obstruction of the catheter by epidermis was observed. It could be demonstrated that pieces of epidermis may enter the catheter, bypassing the bacterial filter of the port, and can then clog the tip of the catheter. PMID- 2330432 TI - [The effect of the Tuohy cannula on the positioning of an epidural catheter. A radiologic analysis of the location of 175 peridural catheters]. AB - The aim of this study was to determine at which lumbar spinal level the tips of different epidural catheters may be located following insertion through cranially directed Tuohy needles. Previous studies varied with respect to materials and methods and may have left the false impression that different types of catheters are necessary or actually more advantageous for particular needs. MATERIALS AND METHODS: One hundred seventy-five trauma patients scheduled for surgery on their lower extremities received continuous epidural anesthesia. With the patient in a sitting position, a midline lumbar puncture was made and one of six different plastic catheters advanced 5 cm beyond the tip of the Tuohy needle. Postoperatively the catheters were filled with Iopamidol and ap X-rays taken of the lumbar spine. The catheter tips were declared to be "cranial" if they were more than 2 cm above, "caudal" if they were more than 2 cm below, and "equal to" if they were within 2 cm of the puncture site. RESULTS: Of the 175 documented catheter tips 47.7% assumed a cranial position, 9.2% were in a caudal position, and 43.4% remained within the level of insertion. A statistical analysis comparing catheter tip location among the six epidural catheter models tested did not reveal any significant differences. DISCUSSION: In a clinically controlled study based on the Tuohy principle of inserting catheters through a needle with a Huber point, different epidural catheter models were inserted into the lumbar epidural space and their locating radiologically documented. It was shown that 52% of the epidural catheters that had been advanced 5 cm into the lumbar epidural space through a cephaled-directed Tuohy needle did not reach the intended spinal level cranial to the puncture site. The results are similar to those of earlier studies, which were not systematic and involved a variety of methods and materials. One reason for the unreliable ascension of the catheter tips may be the many structures within the epidural space which may dislodge and divert the catheters during advancement. In addition, it has sometimes been observed that a change in the patient's position may cause a spinous process cranial to the puncture site to exert pressure and traction on the catheter, partially dislodging it. It must thus be concluded that the use of a Tuohy needle cannot guarantee cranial ascension of an epidural catheter in the lumbar epidural region. PMID- 2330433 TI - How much cancer can EPA regulate away? PMID- 2330434 TI - House fire: a source of dioxins. PMID- 2330435 TI - [Q fever with dilatation of liver sinusoids and a long course]. PMID- 2330436 TI - [Adult Still's disease treated with a bolus of methylprednisolone]. PMID- 2330437 TI - [Arthritis caused by Pneumococcus]. PMID- 2330438 TI - [Vitamin D as immunomodulator factor]. PMID- 2330439 TI - [Changes in the cerebrospinal fluid in patients with HIV infection]. AB - Spinal fluid from 53 HIV infected patients has been reviewed. A diagnosis was made exclusively from the spinal fluid exam in 15 cases while in 15 others it contributed to diagnosis together with other exams. The exam did not contribute any positive data in 23 cases. AIDS diagnosis was obtained in 11 patients by the spinal fluid exam. The most frequently occurring disease was infectious meningitis (10 cases) being 3 of them HIV aseptic meningitis. In our experience, a spinal fluid exam in HIV infected patients and fever of unknown origin did contribute useful data for the diagnosis of AIDS in a large number of cases. PMID- 2330441 TI - [Mixed cryoglobulinemia secondary to Mediterranean boutonneuse fever]. AB - A clinical case of Mediterranean Boutonneuse Fever (MBF) with circulating cryoglobulins during the acute phase, with no clinical symptoms is described and considered an epiphenomenon of the infection. The possible relationship between the infection and the cryoglobulinemia are discussed. The patient is also added to the increasing list of patients reported of Boutonneuse Fever in the Mediterranean area during the observation period. PMID- 2330440 TI - [Antilymphocytic sera versus azathioprine, combined with cyclosporin and steroids, in liver transplant. Comparison of the results at the intensive care unit and 2 years' follow-up]. AB - The use of anti-lymphocyte globulins (ATG, ALG, OKT3) for the control or organ rejection in humans, has been of major importance both in preventing and treating organ rejection resistant to other treatments. We present here the results of our immunosuppression protocol using two different therapeutic associations. To the first group consisting of 29 patients, low doses of cyclosporine, steroids and anti-lymphocyte globulins were given, and to another group of 11 patients azathioprine was given together with cyclosporine and steroids at the same doses as in the first group. We want to point out that the incidence of acute rejections was similar in both groups (17.2% vs 18.1%) immediately after surgery and a greater incidence of rejections at a later time during the follow up period in the group treated with azathioprine (34.4% vs 54.6%). The incidence of chronic rejections was similar in both groups (10.3% vs 8.9%). During the follow up period, the incidence of infections was higher in the group treated with azathioprine (13.7% vs 36.4%) as well as bacteremia episodes (17.2% vs 45.4%) (p less than 0.1). We also want to highlight that patients with graft complications (primary graft rejection) suffered infections (p less than 0,001) and had a higher mortality rate (p less than 0,05) in association to the infection. PMID- 2330442 TI - [Medullary compression at the C6 level as the first sign of multiple hereditary exostoses]. PMID- 2330443 TI - [Left retroparathyroid mass in a patient with surgically treated thyroid papillary carcinoma 4 years earlier]. PMID- 2330444 TI - [Infection of the clean surgical wound (1985-1987) in general surgery]. PMID- 2330445 TI - [Evaluation of mental status in elderly patients]. PMID- 2330446 TI - [Severe infection in systemic lupus erythematosus]. PMID- 2330447 TI - [Real incidence of fibrinolysis in acute myocardial infarct at a regional intensive care unit]. PMID- 2330448 TI - [Normofunctional thyroid hemiagenesis]. PMID- 2330449 TI - [Endocarditis caused by Cryptococcus on a native valve, in a patient with AIDS]. PMID- 2330450 TI - [Myocardial viability estimated on the basis of cellular metabolism]. PMID- 2330451 TI - [Myocardial viability evaluation by nuclear cardiology]. PMID- 2330452 TI - [Electrocardiographic signs possibly related to myocardial viability in patients with old myocardial infarction]. PMID- 2330453 TI - [Viability in ischemic myocardium treated with intracoronary thrombolysis]. PMID- 2330454 TI - [Protection of myocardial viability during cardiac surgery]. PMID- 2330455 TI - [Effects of lung volume levels and trapidil on transdiaphragmatic pressure in young healthy subjects]. AB - Effects of lung volume levels, and effect of intravenous administration of Trapidil on the maximal force developed by the diaphragm were investigated by the measurement of transdiaphragmatic pressure (Pdi) in 10 healthy young subjects. To evaluate transdiaphragmatic pressure, delta Pdimax was used. delta Pdimax was calculated by the subtraction of the transdiaphragmatic pressure at FRC (Pdi FRC) from the maximal transdiaphragmatic pressure (Pdimax) at each lung-volume level. Regardless of the administration of Trapidil, delta Pdimax was highest at FRC in each subject. When Trapidil was administered, Pdimax increased in cases where absolute Pdimax FRC was initially low. The relation between changes of delta Pdimax at FRC after Trapidil administration and delta Pdimax showed significant linear correlation (r = -0.85, p less than 0.002). These results suggest that FRC is the most adequate lung volume level to produce an effective transdiaphragmatic pressure, and that Trapidil increases the muscle force of the diaphragm in cases where the force is initially low in young healthy subjects. PMID- 2330457 TI - [Transient abnormal Q waves under acute myocardial infarction in patients with pneumoconiosis]. AB - Abnormal Q waves have been generally considered to be one of the most reliable indicators of permanent myocardial cell death, namely myocardial infarction. Pathological and experimental studies also support this concept. However, some cases of abnormal Q waves disappearing after myocardial infarction have been reported. Recently, we observed acute myocardial infarction with pneumoconiosis. In this case, a patient with abnormal Q waves appeared within 24 hours after the onset of acute myocardial infarction. But, thirteen days later, these abnormal Q waves disappeared on the surface twelve-lead ECG. The precise mechanism for regression or disappearance of abnormal Q waves is not yet well known. Several studies pointed out a relation of this phenomenon to myocardial collateral circulation under ischemia. And, Nonkin et al reported that, patients with chronic lung disease such like pneumoconiosis, had high incidence of collateral circulation to the myocardium. This was due to chronic hypoxic conditions. In our case, cineangiographic study could not be performed, but disappearance of abnormal Q wave (so called Transient abnormal Q waves), following acute myocardial infarction may be related to the presence of chronic lung disease. PMID- 2330456 TI - [Impairment of erythrocyte anti-oxidant defense mechanisms in hypoxemic patients]. AB - Defense mechanisms against lipid peroxidation were studied in erythrocytes from hypoxemic patients. The levels of lipid peroxides in patients erythrocytes were higher than those of control subjects (15.3 +/- 10.9 vs 7.5 +/- 3.0, p less than 0.05). The levels of reduced glutathione (GSH) decreased in erythrocytes from the patients (426 +/- 108 vs 756 +/- 201, p less than 0.01). Activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were lower than those of control subjects (GPX; 27.6 +/- 7.1 vs 35.1 +/- 3.8, SOD; 76.6 +/- 42.9 vs 125.7 +/- 40.1, p less than 0.01). Positive correlations were observed between the levels of arterial oxygen pressures (PaO2) and the GSH concentrations, the activities of GPX and SOD, respectively. These data suggest that decreased anti oxidant activity enhances lipid peroxidation in erythrocytes from hypoxemic patients. PMID- 2330458 TI - [A case of cardiac tumor found during examination in orthostatic hypotension]. AB - We report a case of left atrial myxoma found when examination was made for the cause of orthostatic hypotension. The case was that of a man of 61 years of age. For the previous 2 years, the man had felt dizzy only at the standing or sitting position. The blood pressure was 90/50 at recumbency and 64/40 at the sitting position. Echocardiographic study revealed a left atrial tumor, which fell into the left ventricular cavity and prevented the blood from filling the left ventricular cavity. This effect was more severe at the sitting position than at recumbency. Resection of the tumor was carried out. It was a myxoma with a diameter of 3.5 cm with a stalk adhering to the postero-inferior wall of the left atrium. After the removal of the tumor, the patient's complaint and orthostatic hypotension disappeared; blood pressure was 102/60 at recumbency and 98/64 at sitting position. Orthostatic dizziness has been reported in some cases as one of the symptoms of the intracardiac tumor. But the state of aggravation at the sitting position has never been observed during actual echocardiographic study. The myxoma adhered to the postero-inferior wall of the left atrium, which site might be associated with the symptom (orthostatic hypotension). PMID- 2330459 TI - [Two cases of primary artery dissection]. AB - We experienced two cases of primary coronary artery dissection. (Case 1) 55-year old man had frequent episodes of chest oppression at early morning and midnight. During chest oppression, electrocardiogram showed transient ST-segment elevation in leads II, III, and a VF. Then, he was diagnosed as having angina pectoris. This diagnosis was based on the fact that he presented coronary spastic syndrome. Right coronary angiogram demonstrated an intimal flap and false lumen at segment 3, and primary coronary dissection was confirmed. (Case 2) A 27-year-old woman complained of back pain while taking a bath. Electrocardiogram showed ST-segment elevation and abnormal Q in leads V2, V3 and V4. She was diagnosed as having acute anterior wall myocardial infarction. Presence of coronary artery dissection at segment 6 was identified by left coronary angiogram. Primary coronary artery dissection is clinically diagnosed by coronary angiogram very rarely. Only 27 such cases have been reported. It was speculated that, in case 1, vasospastic angina may be associated with primary coronary artery dissection. Case 2 had primary coronary artery dissection at segment 6 of the left anterior descending artery. Thus, her clinical picture was similar to those of previously reported cases. PMID- 2330460 TI - [Cardiac arrest episodes by cardiomyopathy following total pancreatectomy, a case report]. AB - A 47-year-old man with advanced pancreatic carcinoma underwent total pancreatectomy with resection of the involved portal vein. His postoperative course was complicated by a couple of cardiac arrest episodes. The first episode occurred seven weeks after surgery during drip infusion of CDDP, and later on during the thirteenth week after surgery. There was no apparent cause for those episodes. On both occasions resuscitation was performed adequately. The second arrest was followed by deep inverted T waves on ECG, however, not by elevation of serum CPK-MB. Because of this, myocardial infarction was ruled out. The diagnosis of cardiomyopathy was made possible through the discovery on the echocardiogram of a hypertrophied left ventricle with thick interventricular septum. Then, on catheterization, myocardial squeezing in the left anterior descending coronary artery was noticed. Finally, histological findings concerning the biopsied cardiac muscle led to the same diagnosis. Cardiac arrest in this case seemed to be due to arrhythmia caused by cardiomyopathy. Echo cardiography should be routinely used as part of the examination prior to extended major surgery. PMID- 2330461 TI - [The effect of pressure support ventilation on breathing patterns and the work of breathing]. AB - We assessed breathing patterns during pressure support ventilation (PSV) and its relationship with the work of breathing in 10 postoperative patients. With increasing levels of pressure support, minute ventilation and tidal volume increased with a decrease in respiratory frequency. Increased minute ventilation was achieved by increased mean inspiratory flow. Duty cycle, however, decreased with PSV. This decrease might allow the diaphragm a longer rest period between contractions, which might decrease the risk of diaphragmatic fatigue. Furthermore, PSV reduced the inspiratory work added by a ventilator to near zero. Oxygen consumption was also decreased with PSV. We conclude that PSV improved the breathing patterns and minimized the work of breathing spontaneously via a ventilator. PMID- 2330462 TI - [Pulmonary lesion of paraquat poisoning on high resolution CT]. AB - It is well known that paraquat causes severe organ-toxicity and pulmonary damage. We observed the progress of a patient who survived paraquat poisoning, and we recorded the changes in the lung by high resolution CT. The patient was a 35-year old man who attempted suicide by paraquat (Guramoxone 100 ml) ingestion. At the time of hospitalization, there was no respiratory involvement. Five days after ingestion, an X-ray examination showed only indistinct vascularity of both lung fields, but high resolution CT showed increased density in the central part of both lung fields. According to the clinical progress after ingestion, mediastinal and subcutaneous emphysema were noted by chest X-ray examination. On the other hand, severe interstitial pneumonia progression of severe lung fibrosis with a decrease in lung volume and interstitial pulmonary emphysema in addition to mediastinal, subcutaneous emphysema were seen by high resolution CT. High resolution CT is useful for detecting morphologic change and diagnosing clinical stages. Observing the course of changes by high resolution CT is useful for deciding the course of clinical therapy, and we have no hesitation in affirming that it should be used in such cases. PMID- 2330463 TI - [A case of right-sided infective endocarditis in a drug addict]. AB - A 49-year-old man was admitted to Mitsui Memorial Hospital because of fever of unknown origin. Since one year ago, he had often used intravenous narcotic drugs. Ten months before his admission, he had his first experience of fever and a chill. Four months later, he was admitted to a hospital under the diagnosis of pneumonia and he was treated successfully. After his discharge, he began to use drugs again, which resulted in the repetition of fever and chills during four months prior to his admission to our hospital. On admission, physical findings concerning the patient were unremarkable, except for mild hepatomegaly. ECG and chest X-ray were normal. Laboratory data revealed marked inflammatory changes and severe liver injury. Blood culture disclosed Campylobacter fetus and two dimensional echocardiography showed a large vegetation on the anterior tricuspid valve. He was diagnosed as isolated tricuspid infective endocarditis accompanied with acute hepatitis due to drug abuse. Moreover pulmonary perfusion scintigraphy showed decreased perfusion in the right lower lung field, which suggested that pneumonia of six months ago was due to septic pulmonary emboli from the infected tricuspid valve. The combined antibiotics therapy was successful. By the follow up echocardiographic studies, the size of vegetation was observed to decrease progressively. PMID- 2330464 TI - [Opto-chiasmatic tuberculoma disclosed by unilateral exophthalmos. Clinico pathologic study]. AB - We report the clinico-pathological case of a 3 year-old boy who presented with progressive unilateral exophthalmos for 6 months. There was a tuberculous meningitis and at post mortem examination an opto-chiasmatic tuberculoma with features of chronic inflammation, epithelioid cells, giant cells and a tuberculoma in the left insula with features of acute inflammation. PMID- 2330465 TI - [Improvement of Joseph's disease with sulfamethazole-trimethoprim]. AB - A case of Joseph's disease characterized by spasticity in all 4 limbs, dystonia and disorders of ocular motility was considerably improved by cotrimoxazole, which confirms a recently published case. Further studies are required to establish this therapeutic effectiveness. PMID- 2330466 TI - [Amyotrophic lateral sclerosis syndrome and hyperthyroidism. Cure with antithyroid drugs]. AB - We report the case of a 62-year old man presenting with generalized muscular weakness, amyotrophy, dysarthria and dysphagia. Neurological examination showed bilateral pyramidal signs and lingual fasciculations. The clinical diagnosis was amyotrophic lateral sclerosis, since only shivers and weight loss pointed to hyperthyroidism. However, after several months the patient developed typical manifestations of hyperthyroidism. After treatment of hyperthyroidism, the neurological symptoms disappeared. Although this association is extremely rare, one must have in mind the possibility of thyroid dysfunction when studying patients with amyotrophic lateral sclerosis. PMID- 2330467 TI - [Cervicodorsal subdural hematoma caused by coumarinic rodenticide poisoning]. AB - A 59-year old man developed subacute tetraparesis following severe sudden neck pain. MRI showed a subdural cervical hematoma. Prothrombin complex activity was low. An unusual coagulopathy after rodenticides exposure was found. Diphenacoum, an effective antagonist of vitamin K1, was present in the patients plasma. Specific medical management led to a complete recovery. Follow-up MRI seventy days later confirmed the complete disappearance of the hematoma. PMID- 2330468 TI - [Dense middle cerebral artery: etiologic significance and prognosis]. AB - Five cases of infarction in the territory of the middle cerebral artery (MCA) are reported. The main feature common to these 5 cases was the presence at CT without contrast injection, in the first 24 hours, of a spontaneous hyperdensity of the ipsilateral MCA. In one case, angiography demonstrated that this hyperdensity was associated with occlusion. In 2 other cases, doppler examination showed occlusion of the internal carotid artery. The transient character of these radiological findings is underlined. In the acute phase of an infarction, hyperdensity of the MCA at an early CT scan without contrast injection suggests an occlusive mechanism and massive infarction with poor clinical outcome. PMID- 2330469 TI - [Spinal cord ependymoma: contribution of MRI using gadolinium]. AB - In a case of panmedullary ependymoma, a rare tumour, MRI was performed before and after gadolinium injection. The latter clearly demonstrated the borders of the tumour. Throughout the procedure, neurophysiological exploration was carried out with recording of motor and somatosensory evoked potentials. PMID- 2330470 TI - [Conference at the Salpetriere. March 1989. Rapid paraplegia, chronic arachnoiditis and hemispheric contrast enhancement in the x-ray scanner]. PMID- 2330471 TI - Comparison of cardiovascular responses to noise during waking and sleeping in humans. AB - Eighty subjects, 40 men and 40 women, were allocated to one of two groups according to their self-estimated high or low sensitivity to noise. In the first part of the experiment, they were exposed to sequences of common noises during the morning or the afternoon. The heart-rate and finger-pulse responses were measured and recorded in relation to sensitivity, sex of subjects, and time of day. The different types of noise were compared for both responses. The heart rate response showed differences between sensitivity groups but not between noises. In contrast, no significant differences were obtained between sensitivity groups when using the finger-pulse response, but clear differences were observed between noises. In a second part of the experiment, 10 men and 10 women subjects were selected from the previous two sensitivity groups. These 20 subjects were exposed during sleep to the same noises as during the daytime. Heart-rate and finger-pulse responses during sleep were significantly greater than during waking, and they did not differ significantly with respect to sensitivity to noise or gender. These two autonomic responses showed differences between noises that appeared to be related to their noise-equivalent-level value. Compared with the silent baseline night, the sleep pattern showed no significant modification in the night of noise disturbance, except for the frequency of transient activation phases, which was significantly increased in the latter. PMID- 2330473 TI - Breathing during sleep in normal middle-aged subjects. AB - Although ventilation during sleep has been studied in normal young and elderly subjects, little data are available concerning possible quantitative changes in ventilatory parameters in normal middle-aged subjects. We studied the occurrence of respiratory events and the changes in minute ventilation, tidal volume, and respiratory rate during rapid-eye-movement (REM) and non-REM (NREM) sleep in 40 normal (20 men and 20 women) middle-aged subjects, using polysomnography with pneumotachography and oximetry. Apnea indices greater than 5, with apneas predominantly of the obstructive type, were found in 17.5% of the subjects (30% of the men and 5% of the women). These "apneic" subjects differed from the "nonapneic" subjects only in that they had a higher body mass index. Minute ventilation decreased from wakefulness to sleep by 14% to 19%, owing to a decrease in tidal volume without a significant change in respiratory rate. This decrease was not greater in slow wave (stage 3-4 NREM) or in REM sleep than in stage 2 NREM sleep, nor was it greater in men than in women. It correlated with the minute ventilation during wakefulness: the higher the minute ventilation during wakefulness, the greater the decrease during sleep. The occurrence of respiratory events was not related to the degree of the decrease in minute ventilation from wakefulness to apnea-free sleep. PMID- 2330472 TI - The influence of two behavioral regimens on the distribution of sleep and wakefulness in narcoleptic patients. AB - Thirty-two hours (night-day-night) of polygraphic recordings were performed on 14 patients with a diagnosis of narcolepsy-cataplexy. Half of the patients stayed in bed during the day, whereas the other half were seated at a table. Patients were free to nap whenever they wanted to. Patients under continuous bedrest slept 2-3 times more during the day than patients who were sitting at the table. Rapid-eye movement (REM) sleep and slow-wave sleep (SWS, stages 3 and 4) were nearly absent during daytime sleep in the table group, but not in the bed group. The differential behavioral regimes during the day resulted in different amounts of SWS in the consecutive night sleep. Although SWS increased from the first to the second night in the table group, it decreased in the bed group. This result suggests that the presumably homeostatic regulation of SWS is intact in narcoleptic patients. PMID- 2330474 TI - Morbidity cut-offs for sleep apnea and periodic leg movements in predicting subjective complaints in seniors. AB - Despite its widespread use, the validity of the 5/h morbidity cut-off for the Respiratory Disturbance Index (RDI) or the Movement Index (MI) in determining presence of sleep apnea (SA) or sleep-related periodic leg movements (PLMs), respectively, has not been determined for any aged population. One hundred community resident seniors 60 years of age or older underwent three consecutive nights of polysomnography and also completed conventional measures of subjective sleep-wake complaints (written sleep questionnaire, sleep log, sleep interview) and mood disturbances (Zung Self-Rating Depression and Anxiety Scales, Profile of Mood States, Beck Depression Inventory). Based on the 5/h cut-off, 34% had SA and 58% had PLMs. Despite this, the frequency of subjective sleep-wake and mood disturbance was low across methods of assessment. Groups formed by the 5/h cut off for RDI or MI failed to differ significantly in responses on all subjective sleep-wake and mood measures. Higher cut-offs also were examined and proved weak or ineffective in predicting subjective sleep-wake and mood disturbance. Preliminary investigations suggested that alternative measures of severity of SA (means oxygen desaturation and means duration of apneas or hypopneas) may be better predictors of subjective disturbance than RDI in this population. These findings both (a) demonstrate that the polygraphically identified SA and PLMs which are widespread in seniors tend not to be manifested in self-reported sleep wake or mood disturbance, and (b) illustrate the need for validated morbidity cut offs for SA and PLMs. PMID- 2330475 TI - MESAM: a heart rate and snoring recorder for detection of obstructive sleep apnea. AB - The high prevalence of sleep-related breathing disorders demands the development of ambulatory recording devices that can handle data with a high degree of selectivity and are easy to use and to interpret. A digital device based on the recording of heart rate and breathing sounds was developed. Patients with sleep related breathing disorders can be preselected before they undergo sleep laboratory investigations. Treatment control can be achieved ambulatory, having an initial recording. PMID- 2330477 TI - Polysomnographic assessment of insomnia. PMID- 2330476 TI - Sleep restriction for the inpatient treatment of insomnia. AB - This study evaluates the efficacy of sleep restriction therapy for treating insomnia on an inpatient psychiatric unit. A depressed patient with concomitant chronic pain and severe insomnia was treated with a sleep restriction procedure. This procedure consisted of curtailing the amount of time spent in bed and then gradually increasing it contingent upon improved sleep efficiency. The treatment was found to be effective for increasing total sleep time from an initial baseline of 2.5 h of sleep per night to 6 h of sleep per night at discharge time. Clinical gains were well maintained immediately after discharge and at a 4-month follow-up. PMID- 2330478 TI - Nothing new about insomnia. PMID- 2330479 TI - Variation in process S: effects on sleep continuity and architecture. AB - Given the two-process model of sleep regulation, and the hypothesis that the sleep disorder in depressive illness is a consequence of a deficient Process S, it was predicted that relatively high levels of S would result in enhanced sleep continuity, increased slow-wave sleep (SWS), prolonged rapid-eye-movement (REM) latency, and less REM sleep. These predictions were tested in two studies. In Study 1, the level of Process S (at 0900 h prior to a 3-h sleep episode) was varied by altering the time and duration of prior nocturnal sleep (2400-0300 h, 0300-0600 h, 2400-0600 h). In Study 2, the leve of Process S (at 2400 h prior to an 8-h sleep episode) was varied by studying subjects when they had not napped or had taken 2-h naps beginning at either 1000 or 1900 h. As predicted by the model, SWS varied reliably depending on the level of S at bedrest, as did indices of sleep continuity at night. Contrary to prediction, however, REM sleep was either increased (Study 1) or did not change reliably (Study 2). It is suggested that, contrary to the other aspects of sleep, REM sleep is strongly influenced by circadian and homeostatic processes and that Process S plays a relatively minor role in its regulation. PMID- 2330480 TI - Catheter-related right-sided endocarditis in bone marrow transplant recipients. AB - Bone marrow transplant recipients are at increased risk of severe central venous catheter-related septicemias that may be complicated by endocardial infection. In view of this, we prospectively evaluated 141 consecutive patients receiving allogeneic or autologous bone marrow infusion. Seven (5%) of 141 patients developed eight episodes of a clinical syndrome compatible with catheter-related right-sided infective endocarditis; this diagnosis was confirmed at autopsy in two patients who died. Staphylococcus epidermidis was the most frequent isolate (four cases). Other offending pathogens were, in one case each, Enterococcus faecalis, Corynebacterium jeikeium, Pseudomonas alcaligenes, and Achromobacter xylosoxidans plus Candida species. Three- to 7-week courses of antibacterial therapy were associated with a favorable outcome in six of the seven cases. Infective endocarditis may be a complication of the use of central venous catheters and should be actively sought in septicemic bone marrow transplant recipients. PMID- 2330481 TI - Acute human immunodeficiency virus infection temporally associated with rhabdomyolysis, acute renal failure, and nephrosis. AB - A previously healthy 29-year-old homosexual man presented with a 4-day history of fever, malaise, sore throat, and bleeding gums. Rhabdomyolysis, acute renal failure, and nephrotic range proteinuria were also present. The patient was found to have acute human immunodeficiency virus (HIV) infection confirmed by the presence of HIV antigen in his serum and subsequent evolution of an HIV antibody profile typical of acute seroconversion. A kidney biopsy revealed acute tubular necrosis and mesangioproliferative glomerulonephritis, with tubuloreticular inclusions. In the presence of otherwise unexplained acute renal failure, rhabdomyolysis, or new onset nephrotic syndrome, acute HIV infection should be considered in the differential diagnosis. PMID- 2330482 TI - Spontaneous, nontraumatic gangrene due to Clostridium septicum. AB - Clostridium septicum is a major cause of spontaneous, nontraumatic gas gangrene. Unlike Clostridium perfringens, C. septicum is relatively aerotolerant and thus appears to be more capable of initiating infection in the absence of obvious damage to tissues. Six cases illustrate the clinical setting and fulminant nature of spontaneous gangrene caused by C. septicum. A lesion in the colon such as carcinoma is often present and is presumed to serve as a portal of entry to the bloodstream. Diabetes and leukopenia are also common predisposing conditions; compromise of vital host responses may facilitate proliferation of those organisms that settle out in the tissues. Acute lymphoma or leukemia during a course of chemotherapy is accompanied by damage to bowel mucosa and granulocytopenia, thus predisposing to spontaneous clostridial gangrene. Infection progresses in a fulminating manner; the majority of patients die within 24 hours of onset. Characteristic symptoms and signs include excruciating pain (although a sense of heaviness may be the only early symptom), swelling of tissues, crepitance, and bulla formation. A hallmark of C. septicum infection is the absence of acute inflammatory cells in involved tissues or in bulla fluid. A series of laboratory investigations demonstrated that fluid obtained from a bulla adversely affected the viability, morphology, and function of polymorphonuclear leukocytes (PMNs), which may explain the paucity of PMNs in involved tissues and may in part contribute to the fulminant progression observed in infection due to this organism. PMID- 2330483 TI - Bacteroides fragilis meningitis: report of two cases. PMID- 2330484 TI - On group C beta-hemolytic streptococcal infections in children. PMID- 2330485 TI - Fluconazole: a novel advance in therapy for systemic fungal infections. Dorado Beach, Puerto Rico, 8-9 October 1988. Proceedings. PMID- 2330486 TI - Fluconazole therapy for coccidioidomycosis in Japanese macaques. AB - The South Texas Primate Observatory is the home of more than 200 Japanese snow macaque monkeys and of a small number of vervets. The colony was established to study social behavior in monkey families; consequently, animals range freely over more than 59 acres. During the past 6 years, there have been six documented cases of coccidioidomycosis. In addition, there have been six probable cases and five possible cases. Disease was progressive in all monkeys and was characterized by cough, wasting, and the appearance of draining cutaneous abscesses. Untreated, monkeys usually died within several months. Fourteen monkeys were treated with oral fluconazole; eight improved rapidly, and the others had no response. Four of the monkeys that improved relapsed quickly after fluconazole treatment was interrupted. Two monkeys showed initial improvement, relapsed when fluconazole treatment was interrupted, and again improved when fluconazole treatment was resumed. The present studies suggest that fluconazole may be effective treatment in primates with coccidioidomycosis and that euthanasia is no longer necessary. However, prolonged treatment is necessary, and relapses may occur. PMID- 2330487 TI - Comparison of fluconazole with amphotericin B in treatment of histoplasmosis in normal and immunosuppressed mice. AB - The activities of fluconazole and amphotericin B against Histoplasma capsulatum were investigated. The minimum inhibitory concentrations ranged from 0.12 to 0.47 microgram/mL for amphotericin B and from 16 to 250 micrograms/mL for fluconazole. Fluconazole given orally twice a day for 6 consecutive days compared favorably with amphotericin B given intraperitoneally once every other day for a total of six doses in the treatment of histoplasmosis in normal and leukopenic mice. PMID- 2330488 TI - Drug interactions with fluconazole. AB - Fluconazole, a water-soluble bis-triazole antifungal agent that effectively penetrates the cerebrospinal fluid, is a highly selective inhibitor of the fungal cytochrome P450 system. In single-dose studies, coadministration of cimetidine and fluconazole (100 mg) resulted in an insignificant decrease in the absorption of fluconazole. The coadministration of rifampin and fluconazole (200 mg) decreased both the half-life and the area under the plasma concentration-time curve (AUC) of fluconazole. In multiple-dose studies, fluconazole (50 mg) did not significantly alter the pharmacokinetics of the two steroid components of an oral contraceptive. Coadministration of tolbutamide with fluconazole (100 mg) increased both the maximal plasma concentration and the AUC of tolbutamide without changing levels of blood glucose. The coadministration of cyclosporin A with a low dose of fluconazole (100 mg) was not associated with significant changes in the minimal and the maximal plasma concentrations of cyclosporin A. While higher doses of fluconazole (200 mg) did not affect endogenous steroids, coadministration resulted in changes in the pharmacodynamics of warfarin and the pharmacokinetics of phenytoin and cyclosporin A. PMID- 2330489 TI - Fluconazole for life-threatening fungal infections in patients who cannot be treated with conventional antifungal agents. AB - Fluconazole therapy was evaluated prospectively in patients with serious fungal infections who failed to respond to or could not tolerate conventional antifungal therapy. Patients were enrolled if they had a life-threatening fungal infection and conventional therapy had failed to eradicate the infection, had caused serious toxic reactions, or was contraindicated. Patients were treated with 200 mg/day, a dosage that could be increased to 400 mg/d if the initial response was not satisfactory. AIDS was the underlying risk factor in 65% of 232 patients evaluated in the study and in 85% of 151 patients with cryptococcal infection. Fifty-eight patients had active cryptococcal infection; 74% had a satisfactory clinical response, and 75% of 44 patients became culture-negative. Patients with inactive infection had a relapse rate of 4.5/1,000 patient-weeks. Twenty-three of 30 patients with coccidioidal infection and 10 of 14 patients with candidiasis or another mycosis were clinically improved. Five patients (2%) discontinued fluconazole therapy because of adverse effects possibly attributable to therapy. Fluconazole may be effective in the treatment of serious fungal infections in patients who cannot continue conventional antifungal therapy. PMID- 2330491 TI - [Motivation: its application to public organizations]. PMID- 2330490 TI - Treatment of coccidioidal meningitis with fluconazole. AB - Fluconazole was administered at doses of 50-400 mg/d to 18 patients (15 men, three women) with coccidioidal meningitis. After a mean duration of treatment of 9.8 months, 10 (67%) of 15 assessable patients had responded, one (7%) of 15 had partially responded, and four (27%) of 15 had not responded to therapy. Five (63%) of eight assessable patients receiving fluconazole as sole therapy responded or partially responded. Two patients discontinued fluconazole after initially responding to therapy, and both experienced relapse. The toxicity of fluconazole remains minimal at doses to 400 mg/d. The penetration of fluconazole into cerebrospinal fluid is substantial at all doses studied. Thus fluconazole continues to show promise even as sole therapy against coccidioidal meningitis. Not all patients respond, however, and relapse may be a problem with the currently studied doses and durations of therapy. PMID- 2330492 TI - [Why do old people fall down?]. PMID- 2330493 TI - [The multiple benefits of integral cardiological rehabilitation]. PMID- 2330494 TI - [It is necessary to raise the quality of care]. PMID- 2330495 TI - [To die in a hospital. An experience in a pediatric ICU]. PMID- 2330496 TI - [Nursing and clinical documentation]. PMID- 2330497 TI - [Technology in nursing, an end or a means?]. PMID- 2330498 TI - [Do our students eat correctly?]. PMID- 2330499 TI - [The Braun and Braun-Bohler splints]. PMID- 2330500 TI - [Continuing education. 46. Subject: the behavioral sciences. Topic: the implications of stress for health]. PMID- 2330501 TI - [Analysis of estrogen levels in the urine of pregnant women using liquid chromatography]. AB - The gas chromatography estimation using CHROM IV device enables a simultaneous investigation of oestrone, oestradiol and oestriol in urine. It is possible to use sorption on a solid sorbent PRESEP C 18 TESSEK for steroid extraction from biological material which shortens and simplifies the investigation method. The oestriol results gained by the described technique are compared with the values of total oestrogens estimated by the classical fluorometric method after Ittrich. The linear regression analysis gives the following result: Y = 0.7637x-2.7531, r = 0.9431, p less than 0.001 and confirms the correlation of both methods. PMID- 2330502 TI - [Effect of abnormal gagging reflex on the possibility of aspiration in mentally retarded children]. AB - The gag reflex promoting aspiration was examined in 262 mentally retarded (MR) children followed up for 3 years due to respiratory illnesses. It was present in 24.1% of MR children and in 91.6% in a control group of children, the difference being statistically significant. A similar significant difference was between the number of children with psychopharmaceutical treatment and the incidence of gag reflex impairment in them. The therapeutic influencing of the swallowing reflex by medicaments is contraindicated in MR children for inducing epileptic seizures. The main point is to prevent aspiration as a stimulus for respiratory disease occurrence. The most important measures are a focused attention of the staff during meals and feeding of MR children and its systematic further education concerning these problems. PMID- 2330503 TI - [Human acute leukemia. II. Acute lymphoblastic leukemia. Complex classification of acute leukemia]. AB - Acute lymphoblastic leukaemias originate from cells committed either to T-lineage (T-ALL) or B-lineage (nonT-ALL). Leukaemic cells are classified into these lines according to the expression of lineage specific differentiation markers, which are T-cell receptors, associated with CD3 antigenic complex, for the T-line and immunoglobulins for the B-line. T-ALL seem to be one type of disease, in the B lineage it is possible to distinguish several types of diseases according to clinical findings and immunoglobulin expression. Monoclonal antibodies directed against various surface antigens are used for diagnosis of ALL and their significance in various types of ALL is evaluated. Specificity of diagnostic markers is discussed especially from the point of the so called "mixed acute leukaemias", cells of which should differentiate in myeloid and lymphoid lines. The existence of a single one "mixed acute leukaemia" has not yet been reliably proved with the use of lineage specific differentiation markers. Present knowledge of karyotype findings in acute leukaemias classified according to specific differentiation markers is reviewed and the necessity to introduce a complex classification on this basis is stressed. PMID- 2330504 TI - [Circulatory changes in the rat tibia in dietary calcium and vitamin D deficiency. Effects of age and sex]. AB - In previous experiments (4) we observed in laboratory rats after a low Ca content diet with no vitamin D a decrease of blood flow through bones. In this study we follow whether the effect of the deficit diet is influenced by age or sex of experimental animals. Tibia blood flow in rats is established by 85Sr microparticles, bone density is estimated by weighing the bone under water. After 10 days of feeding by the deficit diet 85Sr-microparticles catchment in young males is decreased to 74% of that of controls, in young females to 61%, blood flow is decreased to 46% and 51% respectively. In older males after the diet the microparticles catchment is significantly decreased to 63%, blood flow is non significantly decreased to 82% (as a result of higher cardiac output). In the category of older females the effect of deficient diet is not demonstrable as regards both microparticles catchment and blood flow. Bone density in preliminary experiment after 40 days of diet is significantly decreased in males of both age categories and in young females, in the main experiment after 10 days of diet it is decreased only in the categories of young males and females. From the results obtained in following the effect of diet deficient in Ca and vitamin D on density and local blood flow in tibia of rats can be concluded 1) that in this respect younger rats are more susceptible, 2) in the category of older males the effect is partly demonstrable in males, but not in females. PMID- 2330505 TI - Berzelius Symposium XIV: Rheumatoid arthritis: a challenge to modern medicine. Lund, Sweden, 10-12 October 1988. PMID- 2330506 TI - Arthritis symposium--50th anniversary of the King Gustaf++ V 80-yr Foundation. Stockholm, 23 May 1989. Abstracts. PMID- 2330507 TI - Spinoffs from AIDS research. PMID- 2330508 TI - GT-1 binding site confers light responsive expression in transgenic tobacco. AB - Light-dependent expression of rbcS, the gene encoding the small subunit of ribulose-1,5-bisphosphate carboxylase, which is the key enzyme involved in carbon fixation in higher plants, is regulated at the transcriptional level. Sequence analysis of the gene has uncovered a conserved GT motif in the -150 to -100 region of many rbcS promoters. This motif serves as the binding site of a nuclear factor, designated GT-1. Analysis of site-specific mutants of pea rbcS-3A promoter demonstrated that GT-1 binding in vitro is correlated with light responsive expression of the rbcS promoter in transgenic plants. However, it is not known whether factors other than GT-1 might also be required for activation of transcription by light. A synthetic tetramer of box II (TGTGTGGTTAATATG), the GT-1 binding site located between -152 to -138 of the rbcS-3A promoter, inserted upstream of a truncated cauliflower mosaic virus 35S promoter is sufficient to confer expression in leaves of transgenic tobacco. This expression occurs principally in chloroplast-containing cells, is induced by light, and is correlated with the ability of box II to bind GT-1 in vitro. The data show that the binding site for GT-1 is likely to be a part of the molecular light switch for rbcS activation. PMID- 2330509 TI - [Antibodies against human immunodeficiency virus in a male homosexual population]. AB - Between August/1987, and February/1988, 60 homosexual-men from Cancun, Q. Roo, Mexico, were studied to determine the prevalence of HIV antibodies (Elisa and Western Blot). Six subjects were seropositive. No relationship was found between HIV antibodies and age, socioeconomic level or sexual intercourse with foreign subjects. The number of sexual partners/month, and the number of sexual intercourse/month were associated with the presence of HIV antibodies. Bisexual practices were found in 43 percent of all the group. Two subjects with HIV antibodies were classified in the phase II of HIV infection, one in phase III, two in phase IV-A and one more in phase IV-c2. PMID- 2330510 TI - [AIDS and social strata in Mexico: the importance of bisexuality]. AB - The prevalence of AIDS in Mexico and the frequency of sexually transmitted risks was analyzed in relation to the socioeconomic strata of the patients. The study was based on the obligatory notifications of AIDS received by the Ministry of Health between 1982 and september of 1988. The findings show that AIDS is accumulating more rapidly among the low socioeconomic strata, where the bisexual and heterosexual risk factors are also more frequent. These findings are explained in the context of the sexual mores and living conditions of the low social strata of the country. The study leads to the recommendation of diversified preventive activities that meet the peculiarities of the various social strata in Mexico. PMID- 2330511 TI - [Ethical attitudes related to problems of managing patients with acquired immunodeficiency syndrome]. AB - We evaluated, with a questionnaire, ethical attitudes towards the clinical attention of patients with AIDS in 88 physicians. Most of the surveyed were residents and all were working in two mexican hospitals with experience managing patients with AIDS: The National Institute of Nutrition and the National Institute of Respiratory Diseases. None of the questions was answered similarly by all physicians and some of them considered ethically unquestionable, behaviours that traditionally are immoral or even illegal. Reproducibility of the results, evaluated in 10 doctors 5 months later, was acceptable. Ethical attitudes were heterogeneous and inconsistent in the surveyed. This can be the results of a poor or absent training in Medical Ethics in medical schools and during residencies. We believe this deficiency helps maintaining discriminatory attitudes against patients with AIDS and may decrease the quality of medical services to the group. PMID- 2330512 TI - [Effects of health legislation against HIV in blood donation in Guadalajara, Mexico]. AB - In Mexico, since may 1986, the mandatory detection of antibodies against HIV in blood and derivates for the use by humans was legislated, one year later the prohibition of blood trade took effect. The impact of the Sanitary Normativity in the seroprevalence of anti HIV antibodies between blood donors one year before and one year after it took result was compared. A sample was taken from 4743 serums of donors of 6 blood banks in Guadalajara between june 1986 and june 1988; 4020 in the first year and 723 the next. In all the samples the presence of anti HIV antibodies was determined by the ELISA assay and the positive ones were confirmed by indirect immunofluorescence and by Western blot. During the first year, the seroprevalence fluctuated between 2.02 and 30.15 percent depending on different factors, differing from the second year where the seroprevalence was 0.14 percent. It is concluded that the mandatory detection of antibodies against HIV and the prohibition of blood trade, have been definitive factors to decrease the incidence of HIV in blood donors. PMID- 2330513 TI - [Evaluation of the cold chain during the national antipoliomyelitis vaccination days. Mexico, 1987-1988]. AB - An evaluation of the cold chain used during the "National Vaccination Days Against Poliomyelitis" in January and March of 1987 and 1988 was performed in 32 states of Mexico, both the potency of the trivalent Sabin vaccine and completion of requirements for the maintenance of the cold chain were evaluated at each level in the Ministry of Health's structure. Only 56 percent of the refrigeration units exclusively stored vaccines, more than 10 percent of refrigerators were broken, and 44 percent of the persons responsible for the cold chain system considered the storage capacity inadequate. A correlation was found between non fulfillment of maintenance requirements for cold chain and a decreased in vaccine potency. PMID- 2330514 TI - [Enzyme immunoassay (ELISA) for detecting S. aureus enterotoxins B and C in milk]. AB - Staphylococcus aureus enterotoxins B and C, were obtained from strains 243 and 361 respectively. An immunoenzymatic technique was standardized both quantitative and qualitatively. We were able to detect enterotoxin to nanogram level on extracts from artificially contaminated milk. This ELISA immunoenzymatic technique implemented by us under the operative conditions of our working environment, resulted to be easy to handle, consumes only a short time, has a low cost and great diagnostic sensitivity. PMID- 2330515 TI - [Salmonella in raw meat: a study in towns of the state of Guerrero]. AB - Gastroenteric and diarrhoea diseases are the second cause of morbidity in the state of Guerrero, Mexico. Many cases are the result of salmonella in food. 336 meat samples, collected from nine towns in Guerrero state, were analyzed to check the presence of Salmonella. 109 samples (32.44%) were contaminated with this bacterium The kinds of meat with salmonella mainly were: sausage, pork meat and cured meat. The microbiology quality was little deficient in this products. PMID- 2330516 TI - [The impact of AIDS on the health care system]. AB - Since the AIDS epidemic was first detected, it has had a profound influence on the organization of health services in the United States. In this essay, some of the more relevant aspects of this process are analyzed, and the main problems that need to be confronted in order to fight successfully against this serious disease are briefly stated. PMID- 2330518 TI - [Education in public health in 2005. Prospects for strategic planning, progress and perspectives]. AB - The program of Master of Arts in Public Health, one of the academic programmes of the School of Public Health of Mexico, has been through a continuous process of assessment and redesign since january 1988. This process is based on the following aspects: diagnosis of the general academic situation in 1985; re definition of the Schools' objective; design of the academic and administrative modernization process; creation of the area of Academic Programmes, and development of a project on Prospective Planning in Education in Public health to 2005. The first diagnosis of the programme showed problems within the sequence and integration of its curricular contents as well as a lack of coherence between the objectives established and the expected graduates profile. Matters such as population and environmental health were almost not considered. Through on active participation of the whole faculty, a first redesign of the programme was done. After its implementation the programme went into an evaluation process, which showed that most of the problems were solved. The remaining were eliminated through another assessment process, which final outcome was the 1989 program. As it can be seen, the programme has been going through a continuous process of review and updating. The next phase within this process will come one the project on Prospective Planning in Education in Public Health to 2005 is finished. PMID- 2330517 TI - [Prevention of HIV infection in adolescents and young adults]. AB - The prevention of HIV infection in school and university communities acquires great importance in adolescents and young adults where the risk of HIV infection is caused by age, occupation, location, and also adjoining relations with other groups of high incidence of infection, such as teachers and administrative employees. Adequate strategies for specific groups are needed. This paper focuses on the strategies developed at the National Autonomous University of Mexico. An interdisciplinary health commission for the prevention and control of AIDS was established to inform the student body. Other activities performed by this commission include providing medical and psychological attention for AIDS victims, as well as detecting and carrying out follow-up studies of infected students. Efforts in health education have also been made by training professors to include preventive measures against this disease as part of their subject matter. Specific, organized, and immediate action must be taken by health personnel and community organizations in order to prevent HIV infection in adolescents and young adults. PMID- 2330519 TI - Problems in the diagnosis of childhood tuberculosis. PMID- 2330520 TI - Cardiology and cardiothoracic surgery in Cape Town. PMID- 2330521 TI - Temperature-sensitive genes in reproductive and developmental biology--almost 30 years from fruitfly to bedside. PMID- 2330522 TI - Criteria for the notification of childhood tuberculosis in a high-incidence area of the western Cape Province. AB - The medical records of 124 children notified from Ravensmead Clinic, Parow, as having tuberculosis during 1987 were reviewed in order to determine the strength of the evidence on which the diagnosis was made. Arranging the diagnostic criteria in an hierarchical manner, as suggested by the World Health Organisation, the cases were categorised as suspect, probable or confirmed. Twenty-five were suspect cases (20%), 89 probable cases (72%) and the remaining 10 confirmed cases (8%). These findings indicated that notifications from the clinic were being made in accordance with internationally accepted practice. The use of the WHO approach for the categorisation of childhood tuberculosis cases is recommended for both clinical and epidemiological purposes. PMID- 2330523 TI - The booster effect with repeat tuberculin testing in children and its relationship to BCG vaccination. AB - One hundred and twenty-seven children, aged 6 months - 14 years, attending a day care centre in Pretoria had two Mantoux tuberculin tests performed 8 weeks apart. On initial testing 19.7% of the children had reactions greater than or equal to 10 mm and positive tests were commoner in the older children--who had received BCG vaccination twice. On repeat testing a significant increase in the mean tuberculin reaction size was noted and 13% of the children converted to tuberculin positivity. Since an extensive search revealed no evidence of active tuberculosis in either children or adults at the day-care centre, it was concluded that the observed enhancement of the tuberculin reactions was due to the booster effect. This phenomenon was most marked in preschoolers with a BCG scar. It is important to recognise that boosting can occur in children and may be confused with true conversion to tuberculin positivity caused by infection with Mycobacterium tuberculosis. PMID- 2330524 TI - Features of systemic sclerosis (scleroderma) in South African goldminers. AB - Systemic sclerosis is more common among men exposed to silica-containing dust than in the general male population. The clinical features of systemic sclerosis in a group of 24 black goldminers are described. The better-known presenting features of systemic sclerosis, including Raynaud's phenomenon and dysphagia, were rare in this population. Initial presentation was usually with nonspecific features including swelling of the feet or hands, weakness, arthralgia or symptoms of respiratory or cardiac disease. Clinical evidence of pleural or pericardial involvement was more common than is usually described in non occupational systemic sclerosis. Interstitial lung disease was frequently encountered and renal disease was rare. PMID- 2330525 TI - Six-month intermittent chemotherapy for tuberculosis in the Mseleni Health Ward of KwaZulu. AB - Three hundred and seventy-three tuberculosis patients in a rural African setting were treated with a 6-month twice-weekly chemotherapy course. The recurrence rate for those with caseating pulmonary tuberculosis was 7.3% overall. In the second stage of the study, a modified form of supervised ambulatory therapy was used and compliance rates and recurrence rates assessed; 84.8% achieved 90% or more compliance and the recurrence rate was 8.7%. PMID- 2330526 TI - Knowledge and beliefs about tuberculosis among non-working women in Ravensmead, Cape Town. AB - The results of a community-based survey on knowledge and beliefs about tuberculosis in non-working women are presented. The women in the sample showed a very good knowledge of the important aspects of tuberculosis: 90% were aware that it is a problem in their area; 97% knew that it affects the chest; 94% said that it could be fatal; 85% considered it to be infectious and 88% knew that the local clinic provided treatment. Their knowledge of symptoms was good overall but the study revealed misconceptions about the causes and transmission of tuberculosis; 16% indicated that they would not be keen to associate with people with tuberculosis owing to fear of infection. The design effect of cluster sampling was considered in the analysis. The highest design effects (i.e. the most clustering of responses) were found for responses to questions on the causes of tuberculosis and places where treatment could be obtained, possibly reflecting that these beliefs are influenced by neighbourhood contacts. Future tuberculosis education in this group needs to build on existing knowledge and awareness and should focus on changing attitudes such as misconceptions about transmission and the stigmatisation of the disease. Health workers face the challenge of changing behaviour in this community to ensure that people with symptoms present early for screening and that people diagnosed as having tuberculosis comply with treatment. PMID- 2330527 TI - Severe tick-bite fever in young children. A report of 3 cases. AB - Tick-bite fever in young children is usually a mild illness with few complications and no mortality. That it may assume a severe form is illustrated by the occurrence of 3 cases admitted to Johannesburg Hospital within 1 week in which 2 patients, 3 and 5 years old respectively, had severe involvement of the central nervous system with epileptiform fits and deep coma and loss of power of speech on recovering consciousness. The third patient, aged 5 years, developed an incipient haemorrhagic state as well as serious involvement of the central nervous system. The severe form of the disease in these patients appears to have been due to unusually virulent strains of Rickettsia conorii, probably acquired from dog ticks in their homes. All patients recovered on appropriate treatment. Two regained their normal speech after many weeks while the third patient's incipient haemorrhagic state rapidly resolved. PMID- 2330528 TI - Steroid-related avascular necrosis and Crohns' disease. PMID- 2330529 TI - Cefaclor associated with intra-oral ulceration. PMID- 2330530 TI - Computed tomographic appearances of a posterior lumbar apophyseal ring fracture. PMID- 2330531 TI - Vascular malformations and pregnancy. AB - Between January 1975 and June 1989, 240 patients with cerebral vascular malformations were treated at Henry Ford Hospital. In 16 of the patients, the treatment was influenced by pregnancy. Eleven of the patients presented with hemorrhage, four with seizures, and one with hydrocephalus. There were no maternal or fetal deaths in the patients presenting with seizure or hydrocephalus. There were two maternal deaths and one fetal death among the cases presenting with hemorrhage. In the patients with seizure or hydrocephalus, the pregnancy was brought to term and obstetric indications used to determine the time and method of delivery. Hydrocephalus was treated by shunting, and seizures with medication. Antiepileptic drug levels fluctuate in pregnancy and hence were closely monitored to ensure therapeutic levels. Vascular malformations are the most common cause of subarachnoid hemorrhage in pregnancy. The risk of rebleed in the same pregnancy is about 27%. If an arteriovenous malformation ruptures during pregnancy and the patient's condition deteriorates, appropriate emergency surgery should be done. In stable patients, our policy has been to bring the pregnancy to term and then electively perform a craniotomy to excise the arteriovenous malformation. PMID- 2330532 TI - Ventriculoperitoneal shunt in cryptococcal meningitis with hydrocephalus. AB - Fourteen patients with cryptococcal meningitis were reviewed. All patients had a ventriculoperitoneal shunt for hydrocephalus. Early recognitions and prompt relief of hydrocephalus were useful for eight patients who showed rapid deterioration of consciousness or signs of cerebral herniation. There was no surgical response in four patients who had had weeks of confusion or mental change. It seems, therefore, that the duration of disturbance of consciousness or change of mentality before shunting is critical in determination of the outcome of the treatment. Ventricular shunting was effective in relieving papilledema in five patients. However, the surgery did not prevent the development of papilledema to optic atrophy and subsequent blindness in two patients. Hence, in addition to hydrocephalus with increased intracranial pressure, conditions such as direct invasion of the optic pathways by Cryptococcus neoformans or optochiasmatic arachnoiditis may be responsible for the visual failure. Ventricular shunting was also helpful in restoring paraparesis in one patient. Of the cerebrospinal fluid determinations, low protein concentration was a favorable indicator for surgery. Of the seven patients who received the surgical procedure before the start of antifungal therapy, four showed a significant improvement despite active infection of the central nervous system. None of the seven patients deteriorated because of the surgical operation. Thus, active stage of cryptococcal meningitis does not contraindicate the necessity of shunting, and premedication with antifungal drugs is unnecessary. Also, no shunt-related morbidity and mortality was seen in this study. PMID- 2330533 TI - Vein of Galen aneurysm presenting with recurrent aseptic meningitis and subsequent spontaneous thrombosis. AB - Clinical and laboratory findings are described in the case of a patient with a vein of Galen aneurysm who presented with recurrent aseptic meningitis for which no etiology could be identified. The patient subsequently developed thalamic and intraventricular hemorrhage associated with partial thrombosis of the dilated vein of Galen. Review of the literature revealed no previously reported association of these conditions. Recurrent cerebral venous thrombosis involving the fistula is hypothesized as the cause of repeated inflammatory reactions near the subarachnoid space. More extensive thrombosis may then have precipitated the hemorrhage. PMID- 2330534 TI - Two surgically cured cases of subependymoma with emphasis on magnetic resonance imaging. AB - The authors describe two surgically cured cases of symptomatic subependymomas located in the lateral ventricle and septum pellucidum with emphasis on magnetic resonance imaging study. Both computed tomography and MRI revealed a calcified mass with repeated intratumoral hemorrhages. Cerebral angiograms disclosed rather hypovascular lesions. The histologic diagnosis was proven to be of subependymoma. The pertinent literature of surgically treated subependymomas is reviewed, and the characteristic biologic features are also discussed. PMID- 2330535 TI - Cerebrospinal fluid rhinorrhea in patients with untreated pituitary adenoma: report of two cases. AB - We report the cases of two patients with untreated pituitary adenoma who presented with cerebrospinal fluid rhinorrhea. The surgical treatment and mechanisms involved in this rare condition are discussed. PMID- 2330536 TI - Plasma cell granuloma of the brain. AB - We describe a 29-year-old woman with a plasma cell granuloma arising in the right superior temporal gyrus. The mass appeared on computed tomography as a well circumscribed area of increased density that markedly enhanced with administration of contrast. Microscopic examination showed a mixed cell population with a predominance of plasma cells, including plasma cells showing cytologic atypia, as well as necrosis with polymorphonuclear leukocytes, and the tumor was characterized immunohistochemically by polyclonal plasma cell proliferation. PMID- 2330537 TI - Intramedullary melanotic schwannoma of the cervical spinal cord: report of a case. AB - We present a case report of a patient with an intramedullary tumor of the midcervical cord. At surgery, the lesion was found to be highly pigmented, and pathological analysis revealed a melanotic schwannoma. Intramedullary schwannomas and melanotic schwannomas are exceedingly rare. This is the second reported case of an intramedullary melanotic schwannoma of the central nervous system. PMID- 2330538 TI - International perspective: neurological surgery in Nicaragua, 1989. AB - Despite the hardships of war, underdevelopment, and economic chaos, an active neurosurgical service and training program have been established at Lenin-Fonseca Hospital in Managua, Nicaragua. Using the few available diagnostic and ancillary facilities, a team of European, Latin American, and Soviet neurosurgeons cares for patients suffering from a variety of neurological conditions. Fortunately, the neurosurgical operating room is well equipped, most essential medications are available, and the physicians are well motivated. Over the past 10 years, the number of admissions to the neurosurgical service at Lenin-Fonseca Hospital has grown to over 2000 patients annually. The availability of resources for future improvements in facilities and manpower training depends upon continued international cooperation and the establishment of a peacetime economy. PMID- 2330539 TI - The Professional Liability Committee of the American College of Surgeons: some comments on the whole being more effective than the sum of its parts. PMID- 2330540 TI - Is modern-day neurosurgery becoming a cooperative? PMID- 2330541 TI - [Treatment of radiogenic colitis with a rectal foam containing cortisol. Clinical and pharmacologic data]. AB - 20 patients with highly dosed irradiation of the small pelvis had been treated with Colifoam (hydrocortisone) in order to prove the therapeutic effect of radiation-induced proctitis. Over a period of three to six weeks starting in the third week of irradiation all patients received one applicator filling of rectal foam after bowel movement daily. The findings were verified by proctoscopy, histology and subjective personal well being. In ten patients we determined the daily cortisol profiles. Six months post irradiation ten patients underwent barium enema of the colon. During therapy no major complaints were recorded. The proctoscopic findings showed little changes concerning the submucous vascular walls. In none of the patients any kind of late lesion could be observed. The daily cortisol profile did not show any aberration of the physiological patterns. In conclusion the local therapy of Colifoam can be considered an additional treatment of radiation-induced colitis (proctitis). PMID- 2330542 TI - [Nasopharyngeal involvement in Hodgkin's disease--its diagnosis by CT and MRT. A case report]. AB - Lymphocyte predominance subtype of M. Hodgkin with disease of the upper cervical and/or preauricular lymph nodes more often shows simultaneous involvement of nasopharynx. Epipharyngoscopy alone is not always diagnostic. Staging has to be completed by additional computed tomography and/or MRI of the nasopharynx. In case of involvement enlargement of target volume is mandatory. PMID- 2330543 TI - Analysis of the dose-volume histogram in uterine cervical cancer by diagnostic CT. AB - The dose-volume histogram of the target volume during intracavitary irradiation in cases of uterine cervical cancer was calculated from diagnostic computed tomography data in order to study the correlation with prognosis. The minimum dose applied to the target volume was most closely related with the prognosis. However, for the actual planning of three-dimensional treatment, a dose of 80% of the volume of the dose-integration volume curve, on which the histogram was integrated in the order of high dose, was recommended as an index dose for dose optimization. PMID- 2330544 TI - [Cassette-film combinations for the imaging verification of irradiation with 60Co photons up to 42 MV and electrons of 5 to 40 MeV]. PMID- 2330545 TI - [A simple method for positioning and fixing the extremities during the radiotherapy of soft-tissue sarcomas]. AB - The exact and reproducible radiotherapy of malignant tumours in the extremities is aided by reliable positioning of the involved limb. In our department individually-formed casts and circular fix up made of two-component polyurethane foam (NEOFRAKT, supplied by Schumacher, Krefeld, FRG) are used. These allow the maintenance of any bending, stretching and torsional positions. The fields to be applied are cut out of the casts, thus preventing any influence on the depth dose of the radiation involved. PMID- 2330546 TI - Neutron dose planning with the MEVAPLAN system. AB - For treatment planning with fast neutrons the neutron and photon components have to be calculated separately. The data base and the source code of the MEVAPLAN system (Siemens) have been modified to fulfil these requirements. Major changes were made to enable the kerma-corrections for organs of different atomic compositions. Furthermore, the linear attenuation coefficients are used to calculate the transmission of neutrons through different organs. The data can be obtained indirectly from CT data, if the calibration of the CT data into density is known. The DT-neutron generators require a modified inverse square law for different SSD's. The corresponding coefficients are determined and are included in the data base of the system. A comparison between measured and calculated isodoses and treatment plans based on CTs is shown. PMID- 2330547 TI - Radiation response of plasma protein and albumin of peripheral blood and its modification by MPG (2-Mercaptopropionylglycine) in mice. AB - Changes in the total protein and albumin level in the blood of six week and three week old Swiss albino mice exposed to a sublethal dose of 2.2 Gy of gamma rays after an intraperitoneal injection of 20 mg/kg body weight of the radioprotector drug MPG (2-Mercaptopropionylglycine) were studied. The results were compared with those obtained from animals irradiated with the same dose of gamma rays in the absence of the drug. Animals were sacrificed at one, three, five, seven and 14 days after irradiation. The drug has been found to modify the levels of plasma protein and albumin in the blood of the irradiated animals. The depletion observed was less marked in the drug treated animals than their respective controls. The observations have been discussed in light of relevant literature. PMID- 2330548 TI - Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. AB - A previous New Zealand case-control study of asthma deaths in the 5-45 year age group during 1981-3 found that prescription of fenoterol (by metered dose inhaler) was associated with an increased risk of death in patients with severe asthma. One major criticism of this study was that drug data for the cases and controls came from different sources. A new case-control design has been used to evaluate the same hypothesis, with a different set of asthma deaths, the same source for drug information being used for both cases and controls. This depended on identifying deaths from asthma during 1977-81 from national mortality records, and ascertaining which patients from those who died had been admitted to a major hospital for asthma during the 12 months before death. The study was confined to this subgroup, which accounted for about 20% of all asthma deaths in the areas served by a major hospital. For each of the eligible patients who died four age matched controls were selected from patients admitted to hospital for asthma during the year that the death occurred who had also had an admission for asthma in the previous 12 months. For the 58 cases and 227 control subjects information on prescribed drugs was collected from the hospital records relating to the previous admission. The odds ratio of asthma death in patients prescribed inhaled fenoterol was 1.99 (95% confidence interval 1.12-3.55, p = 0.02). As in the previous study, subgroups defined by markers of chronic asthma severity were also considered. The inhaled fenoterol odds ratio was 2.98 (95% CI 1.15-7.70, p = 0.02) in patients prescribed three or more categories of asthma drugs, 3.91 (95% CI 1.79-8.54, p less than 0.01) in patients with a previous admission for asthma in the past 12 months, and 5.83 (95% CI 1.62-21.0, p = 0.01) in patients prescribed oral corticosteroids at the time of admission. In patients with the most severe asthma (defined by a previous admission for asthma during the past 12 months and prescribed oral corticosteroids at time of admission) the inhaled fenoterol odds ratio was 9.82 (95% CI 2.23-43.4, p less than 0.01). These findings add further support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma. PMID- 2330549 TI - Why are hospital admission and mortality rates for childhood asthma higher in New Zealand than in the United Kingdom? AB - New Zealand has higher mortality and hospital admission rates for asthma than England and Wales. To determine the reasons for this the available data on asthma mortality and hospital admissions from the Auckland region of New Zealand were compared with data from the South West Thames Region of England for 1979-86 and data from previous surveys on prevalence of wheeze (Auckland 1985, Croydon 1978). In addition, a survey of general practitioners was carried out to determine their approach to the management of asthma, patient simulations being used. Asthma mortality in children of European descent aged 5-14 years was 2.5 times higher in Auckland than in South West Thames. The reported lifetime, 12 month, and one month prevalences of wheeze were also higher in Auckland (by 18.5%, 32.1%, and 87.5%). Unexpectedly, the hospital admission rate for asthma in children of European descent aged 5-14 years was 5% less in Auckland than in South West Thames. Comparative studies of hospital case notes and of the replies from general practitioners showed that in Auckland the duration of illness before admission was greater and that general practitioners were less likely to admit patients with acute asthma. The overall standard of general practitioner care in Auckland was, if anything, higher than in South West Thames but in both areas there was considerable variation. On balance it was concluded that the higher mortality rate in New Zealand is explained by higher levels of morbidity rather than relative deficiencies in care. Nevertheless, the implications of the lesser use of hospital care for acute asthma observed in Auckland need further consideration. PMID- 2330550 TI - Nosocomial lower respiratory tract infections in surgical wards. AB - A six month prospective study of nosocomial lower respiratory tract infection was conducted in four general surgery wards and one urological surgery ward. Thirty eight cases were identified, representing 1% of the surgical admissions to these wards. Twenty eight of the infections followed abdominal surgery. Six patients died, five of whom had pre-existing cardiorespiratory disease. Potential pathogens were isolated in 21 patients, the commonest organisms being Streptococcus pneumoniae and Haemophilus influenzae. PMID- 2330551 TI - Assessment of reversibility of airway obstruction in patients with chronic obstructive airways disease. AB - Spirometry before and after an inhaled beta agonist or a course of oral prednisolone is widely used to detect reversible airflow limitation in patients with chronic obstructive lung disease. How many of these patients have a response and how the response to beta agonists relates to the response to corticosteroids is not clear. In 127 outpatients (mean (SD) FEV1 0.92 (0.38) 1) who had a clinical diagnosis of chronic obstructive lung disease (continuous breathlessness for more than six months and an FEV1/forced vital capacity (FVC) ratio less than 60%) and who appeared to be stable, the change in FEV1 was measured after salbutamol 200 micrograms from a metered dose inhaler and 5 mg from a nebuliser. Symptoms and spirometric values were recorded before and after two weeks of oral prednisolone 30 mg. Reversibility was defined as a response in FEV1 of 15% or more from baseline alone and as a 15% change and a minimum increase of at least 200 ml. The latter gave results that showed greater internal consistency between the drug regimens. On the basis of this criterion 56 patients (44%) had no response to salbutamol or prednisolone, 71 responded to salbutamol (including all 27 steroid responders), and 25 patients had a response to salbutamol 5 mg but not to 200 micrograms. In general, the largest increase in FEV1 after salbutamol occurred in the subjects with greatest improvement after prednisolone. Subjects showing a response in FEV1 after two weeks' prednisolone had a fall in total symptom score, unlike those who had no response to any treatment or a response to salbutamol only. These data show that reversibility in response to beta agonists is common in patients diagnosed on clinical grounds as having stable chronic obstructive lung disease, that it can be substantial, and that it is best detected by using a larger dose of salbutamol. Salbutamol responders were those most likely to improve after a trial of oral prednisolone. Allowance should be made for the variability of FEV1 in the calculation of the percentage response at low baseline values (less than 1 litre). PMID- 2330552 TI - Does the outcome of the tidal breathing and dosimeter methods of assessing bronchial responsiveness in children with asthma depend on age? AB - As minute volume increases with age, a study was carried out to determine whether the measurement of bronchial responsiveness to pharmacological agents with the tidal breathing technique in children might be influenced by age. Bronchial responsiveness to histamine administered by tidal breathing was therefore compared with that produced with a dosimeter in 25 children with asthma aged 5-18 years. Bronchial responsiveness was defined as the concentration of histamine that caused a 40% rise in pulmonary resistance (PC40) measured by random noise forced oscillation at 6 Hz. Values of PC40 measured by the tidal breathing method were lower than those obtained with the dosimeter method, presumably owing to differences in the dose administered and variations in the pattern of breathing. The difference between the two methods was not related to age, however. It is concluded that the tidal breathing and the dosimeter methods are both suitable for the measurement of bronchial responsiveness in children of various ages and that both can be used in longitudinal studies. PMID- 2330553 TI - Occupational asthma due to tea dust. AB - Three patients are described who had developed asthma after working as tea packers. In two cases the diagnosis was confirmed by serial monitoring of peak expiratory flow rates, bronchial responsiveness to histamine, and specific inhalation challenges in the laboratory. The third patient experienced isolated changes in bronchial responsiveness to histamine after periods of exposure at work and after specific inhalation challenges in the laboratory without showing spirometric changes. Two of the three subjects were non-atopic; none had an immediate reaction to skin prick testing with a tea solution. PMID- 2330554 TI - Cough threshold after upper abdominal surgery. AB - The effect of upper abdominal surgery under general anaesthesia on the cough threshold was studied in 26 patients, on the basis of the concentrations of capsaicin and citric acid causing cough. Cough threshold was determined after administering doubling doses of nebulised aerosols of capsaicin and citric acid before operation and on the first and fourth postoperative days. There was an increase in cough threshold (decrease in cough sensitivity) in response to both inhaled irritants on the first postoperative day from the preoperative day and a return towards preoperative values by the fourth day after surgery. The increase in cough threshold on the first postoperative day correlated with the time since opiate administration (r = 0.7 for capsaicin, 0.52 for citric acid). These results show that the threshold concentration of chemical irritants causing cough is increased on the first postoperative day after upper abdominal surgery. PMID- 2330555 TI - Unilateral post-tuberculous lung destruction: the left bronchus syndrome. AB - In a prospective study of 13 patients requiring pneumonectomy for unilateral post tuberculous lung destruction the left side was found to be affected in 12. Review of a further 172 cases showed the left lung to have been destroyed in 109 (63%). It is suggested that this predominance of the left side is due to the anatomical characteristics of the left main bronchus and that disordered haemodynamics also appear to play a part. PMID- 2330556 TI - Sericulturist's lung disease: hypersensitivity pneumonitis related to silk production. PMID- 2330557 TI - Non-cardiogenic pulmonary oedema due to the intravenous administration of clove oil. PMID- 2330558 TI - Chickenpox pneumonia: an association with pregnancy. PMID- 2330559 TI - Postpneumonectomy pulmonary oedema. PMID- 2330560 TI - Sedation for fibreoptic bronchoscopy. PMID- 2330561 TI - [Clinical pharmacology--a new medical specialty]. PMID- 2330562 TI - [The role of child psychiatry and adolescent psychiatry at somatic pediatric departments]. PMID- 2330563 TI - [The importance of medical history taking in evaluating and monitoring needs in suspected myocardial infarction]. AB - In patients referred to the hospital with a suspicion of acute myocardial infarctions immediate diagnostic accuracy is improved by using a strictly standardized case history upon admission. Thus, the number of patients with proven acute myocardial infarctions erroneously referred to a general ward instead of to the coronary care unit wound have been reduced by one third, and unnecessary referral to the coronary care unit of patients in whom acute myocardial infarctions were not diagnosed would have been reduced by the same amount. Our study emphasizes the important of obtaining a thorough, standardized case history in patients with suspected acute myocardial infarctions. This would improve both patient care and the optimal use of coronary care unit facilities. PMID- 2330564 TI - [Porphyria variegata--the first case in Norway]. AB - In Norway, the most common porphyrias are acute intermittent porphyria and porphyria cutanea tarda. We describe the first case of porphyria variegata in this country. The patient showed symptoms of the skin and had no abdominal discomfort. Her family was also evaluated and two other persons were found with suspected latent porphyria variegata. We discuss the main symptoms of this type of porphyria and the possibilities of treatment. We emphasize that examination of porphyrins in the feces of patients with porphyria variegata is essential for the diagnosis. PMID- 2330565 TI - [Health education in psychiatry]. AB - A more open and community based psychiatry should put more weight on health education and cooperation with the media. In the USA guidelines have been developed for such cooperation. In Norway, media experiences are described from the Oslo and Telemark regions. Exposure in the media can influence the relationship between the patient and the therapist and also influence the therapeutic process. Only few experimental studies have been carried out on the media and primary prevention. The article also briefly reviews mental health education through fiction, autobiography and popular scientific literature etc. PMID- 2330566 TI - [Health education and cooperation with the mass media. Experiences from a set up at the Telemark Central Hospital, psychiatric department]. AB - Since 1983 the Psychiatric Division, Telemark Sentralsjukehus, has had a multiprofessional committee for health education and information directed mainly at the public and the primary health and social services. The main projects have been a series of articles in a local newspaper, arranging "open days" for the public and contributing to the form and content of radio programmes. It is also important to be available to journalists. We have managed to cooperate with the media on psychiatric health education. This has not, however, reduced the interest of the press in bringing conflict-related news and scandal stories from the psychiatric field. Laws and regulations seem to give too little flexibility in health education. Physicians should be better educated on mass communication and how to cooperate with the mass media. PMID- 2330567 TI - [Multi-family groups]. AB - During the last 25 years the author has been a leader of six multi-family groups. The first started in close connection with a psychiatric emergency unit with up to 11 families at the same time. Later, treatment has been defined for four up to six families with generation problems. The patients were children with drug addiction or psychosis, mostly schizophrenia. The dynamic steps of the therapeutic process were information, support, discussion insight and change. PMID- 2330568 TI - [Neck metastases from an unknown primary tumor]. AB - We evaluate 41 patients treated for cervical lymph node metastases from occult primary carcinomas. Minimum follow-up was two years. 18 patients had metastases from squamous cell carcinoma, 12 from undifferentiated and 11 from adenocarcinoma. The survival rate was best for patients treated with surgery and radiation. The survival rate was 66% for patients with squamous cell and undifferentiated carcinoma, compared with 20% for patients with adenocarcinoma. The survival rate was 85% for patients with N1 and N2A metastases (UICC 1987) from squamous cell and undifferentiated carcinoma, compared with 45% for patients with metastases classified as N2B-N3. The prognosis was better for patients with tumors in the upper 2/3 of the neck than for patients with metastases in the lower 1/3 of the neck. We emphasize the significance of fine-needle aspiration biopsy as a highly accurate, safe and valuable technique in diagnosing malignant tumors of the head and neck. PMID- 2330569 TI - [The influence and use of drugs other than alcohol among drivers]. AB - During the last few years, the National Institute of Forensic Toxicology has recorded an increasing number of cases of impaired driving due to drugs other than alcohol. Screening for drug use among drivers who are suspected of drunken driving only have also shown high frequencies of drug positive blood samples, indicating that a large number of drugged drivers are not discovered. Our results also show that the combined influence of both alcohol and drugs is common. Several new regulations were passed by the Norwegian Parliament in 1988 pursuant to the Norwegian Road Traffic Art. These new regulations include differentiation of sentences depending on blood alcohol concentration, introduction of evidential breath alcohol analysis and reduced use of clinical examination. The article discusses today's procedures for handling cases of suspected impairment by drugs. It is concluded that several problems will arise when dealing with cases of combined alcohol and drug impairment in accordance with the new Road Traffic Act, and that the introduction of evidential breath alcohol analysis and reduced use of clinical examination will make it more difficult to detect drugged drivers, particularly when they are also influenced by alcohol. PMID- 2330570 TI - [Interactions between alcohol and drugs]. AB - Interactions between ethanol and drugs are probably frequent, but few quantitative data are available on the magnitude of the problem. The interactions may be either pharmacodynamic (interactions at the site of drug action) or pharmacokinetic (interactions connected to drug absorption, distribution, metabolism and elimination). The most important interactions occur when ethanol and the drug are present in the organism at the same time. These direct interactions usually lead to supratherapeutic effects and unwanted side-effects, caused mainly by pharmacodynamic but also by pharmacokinetic mechanisms. The most serious interactions are seen with drugs which act on the central nervous system, and with anti-inflammatory drugs, anti-hypertensives and warfarin. Chronic drinking (above 50 g ethanol per day) for months may reduce the response to the drug in sober periods. These indirect interactions (increased tolerance to the drug) are due both to pharmacodynamic and pharmacokinetic mechanisms. Ceasing drinking will be followed by an increase in the efficacy of the drug in question. Long-term intake of ethanol (for years) may cause damage to organs, followed by increased sensitivity to many drugs. PMID- 2330571 TI - [Retrograde ileography. Contrast imaging of the terminal ileum by colonoscopy]. AB - The distal ileum, the segment most frequently affected by small intestinal disease, may be difficult to visualize by conventional x-ray techniques. In recent years various methods have been described for retrograde ileography during or after colonoscopy. However, these methods require special equipment and may be difficult to perform in practice. We have therefore tried out a somewhat modified technique. Patients with suspected distal ileal disease are examined on a fluoroscopy table at the x-ray department. When necessary, biopsies are taken during the introduction of the scope. With the tip of the colonoscope in the terminal ileum (or coecum) a catheter is introduced through the biopsy channel into the distal ileum. Water-soluble contrast (Mixobar) is then instilled under fluoroscopic control and films are taken in the supine, oblique and prone positions. Owing to gas already present in the ileum a double contrast effect is obtained. The ileography is completed in 5-10 minutes and entails no additional discomfort for the patient. The technique is easy to learn and requires no special equipment. It does not obviate the need for conventional small bowel enema, but may be a valuable supplement to this examination when distal ileal pathology is suspected. PMID- 2330572 TI - [Intercostal blockade]. PMID- 2330573 TI - [Prevention and treatment of neutropenia. Practical procedures]. PMID- 2330574 TI - [Rationalization of the recording of case histories using a modular system]. AB - Delay often occurs in preparing the case history and treatment summary for transmission to the general practitioner. At the Hagavik Orthopaedic Hospital this delay is reduced to about five days by preparing the summary on a modular system consisting of four modules; the biographical data of the patient, admission and discharge dates and the treatment classified, an abstract of the patient's hospital record and discharge notes. Since 1986 the two first modules have been prepared by computer, which has reduced secretarial work by about one week per 1,000 summaries. PMID- 2330575 TI - [The Heart Center in Oslo. Background, organization and the first results]. PMID- 2330576 TI - [Incidence of extrauterine pregnancy in Noreg in 1986]. PMID- 2330577 TI - Possible urban-rural difference in habitus of school children in Sendai. AB - Right after a large-scale merge involving 2 cities and 2 towns in 1987-1988 to form an enlarged city of Sendai, the body habitus of school children (in the 6th year-grade in primary schools and 3rd year-grade in junior high schools) were compared among the 4 regions (called by the pre-merge names of Akiu, Izumi, Miyagi and Sendai). The analysis showed that primary school boys in Sendai are taller and heavier than the boys in Izumi, and Izumi boys are heavier than Akiu boys. In junior high schools, Izumi girls are taller than Sendai girls with smaller Rohrer's and Quetlet's index. The observation indicates that the difference in body habitus is present in agreement with variation in the extent of urbanization in the regions. PMID- 2330578 TI - Induction of recurrent glomerulitis with accentuated glomerular lobulation by intermittent repetition of unilateral Masugi nephritis. AB - In order to induce a glomerulitis with lobular features, antirabbit renal glomerular basement membrane hen serum was intravenously injected into rabbits repeatedly at intervals of 3 weeks, during the course of clamping of contralateral renal arteries for 20 min. The first injection induced disorganization of the glomerular architecture accompanied by proliferation of local fixed cells and following crowding of the proliferated cells towards the axis of the loops and peripheral recanalization which brought about a lobular appearance of glomerulus. And the repeated injections induced repetition of such processes, resulting in accentuation or exaggeration of the lobular features of the glomeruli. The glomerular lesions presented here resembled closely to those of human lobular glomerulonephritis. Accordingly, the results of this study will offer some clue to understanding of the genesis of the human glomerular disease. PMID- 2330579 TI - Community people's preference of hand drawn face graph as a health informing device. AB - Although the cartoon of a face is an effective device to visualize the image of numerical indices, its use is not popular among community health personnel. In the present study, we used the face graph as an aid for health informing and educating activities in the setting of a community health activity. For this purpose, we designed a special sheet to draw face by hand. By using this sheet, each person can draw his/her 'face' from one's laboratory data index under the guidance of additional lines. The acceptability of this hand drawn face was evaluated by 283 people aged 65 years and over at a health counseling session. For both men and women, a higher percentage preferred face (37% for men, 40% for women) over numeral (23% for men, 17% for women). The preference for the face graph was also observed at each of three age groups within each sex. The highest affinity to face (64%) was observed for the 14 women who reported as cataract patients. PMID- 2330580 TI - Changes of mercury contents in hair of Chinese scholars after they came to Japan. AB - In April 1988, 49 Chinese scholars came to Japan for one year medical training. Their hair samples were collected in June 1988 and March 1989 for analyses of mercury. After they lived in Japan for nearly one year, the mean total-Hg contents in hair were increased from 0.82 microgram/g to 1.96, and those of methyl-Hg in hair, from 0.19 microgram/g to 0.32, both with significant differences (p less than 0.01). It is suggested that Japanese foods, especially the fish, might be the responsible factor in increasing the mercury contents in their hair. PMID- 2330581 TI - Changes in the mixed venous blood oxygen saturation during the acute phase of myocardial infarction and administration of dobutamine. AB - Clinical significance of the continuous monitoring of mixed venous oxygen saturation (SvO2) by Catheter Oxymetry System was evaluated in 45 patients with acute myocardial infarction (AMI). Patients with AMI were classified into 4 groups according to Forrester's hemodynamic classification. The mean SvO2 value for each group was 70.4 +/- 4.1% for subset I, 54.7 +/- 6.9% for subset II, 55.8 +/- 9.8 for subset III, and 47.0 +/- 8.0% for subset IV. Subsets II, III, and IV showed significantly low values compared to subset I (p less than 0.01). The relationship between PCW and SvO2 level was expressed by the negative regression line y = -0.8x + 73.8 (r = -0.64, p less than 0.01). The curve representing the relationship between CI and SvO2 level was expressed by the equation y = 53.8 logx + 42.7 (r = 0.68, p less than 0.01). The SvO2 level of the 14 patients who showed a significantly low value of 56.9 +/- 8.2% before administration of 5 micrograms/kg/min dobutamin, increased to a mean value of 66.8 +/- 7.9%, as well as the CI after 60 min. However, PCW demonstrated no pronounced changes because of dobutamine administration. Since the SvO2 level highly correlated to the cardiac pumping function in acute phase of myocardial infarction, polygraphic monitoring of SvO2 was found to be a useful index for evaluating changes in the hemodynamics. It was also a very useful measure in evaluating the effects of dobutamin. PMID- 2330582 TI - Lectin binding of intrahepatic bile ducts and peribiliary glands in normal livers and hepatolithiasis. AB - Histochemical features of the intrahepatic bile ducts and peribiliary glands were examined with five biotinylated lectins in 12 normal human livers and 12 livers with hepatolithiasis. There was a marked proliferation of peribiliary glands, especially mucous cells, in the stone-containing bile ducts. Based on the carbohydrate binding specificity for each lectin, it was found in both the normal and hepatolithiasis livers, that N-acetylglucosamine, N-acetylgalactosamine, D galactose and L-fucose were abundant in the mucous acinar cells of the intrahepatic peribiliary glands, and mannose (or glucose) was present exclusively in the serous acinar cells and surface lining epithelium. Considerable case to case and cell to cell variations, however, were noted in the expression of lectin binding activity. It has been shown that major monosaccharide components of biliary glycoproteins are N-acetylglucosamine, galactose and fucose. All of these carbohydrates were detected in the peribiliary glands, especially mucous acinar cells, in this study. Therefore, the peribiliary mucous cells are mainly responsible for the secretion of the glycoproteins with these carbohydrates into the hepatic bile, and may play a role in the calculi formation in the intrahepatic biliary tree. PMID- 2330583 TI - Probable assignment of the dihydropteridine reductase gene to 4p15.31. AB - We report the dihydropteridine reductase (DHPR) activity in cases with interstitial deletion of the short arm of chromosome 4. Case 1 with the segment 4p15.32-4p16 deleted has normal DHPR activity. Case 2 with 4p15.2-4p15.32 deleted has reduced DHPR activity, less than 50% of normal. PMID- 2330584 TI - Blood coagulation variations induced by carbon tetrachloride inhalation in Wistar rats. AB - Research into the development of chronic hepatic failure induced by CCl4 inhalation and the effect of this damage on blood coagulation was performed on Wistar rats. Exposure to CCl4 (325 ppm) consisted of the administration of 22, 26, 29, 31, 34, 39, 40, 45, and 49 doses, respectively. To determine and evaluate the nature and degree of CCl4-induced lesions at different stages of the treatment, histological alterations in liver samples were evaluated. Fatty infiltration in the centrilobular parenchymal cells observed after administration of the first doses was seen to spread toward mid- and peripheral zones of the lobules at the highest doses, accompanied by necrosis and nonelastic fibrosis. A causal relationship between liver failure and decrease in plasma fibrinogen levels was not observed, even though CCl4 does reduce protein synthesis. A lack of correlation between changes in reptilase time and quantitative variations in fibrinogen was seen. This finding was confirmed by observations of qualitative modifications in the fibrinogen caused by CCl4 inhalation, such as an increase in sialic acid content, which has been previously described. Activated partial thromboplastin time seems to be a good marker for benign liver damage in carbon tetrachloride intoxication. Nevertheless, prothrombin time does reliably reflect the degree of hepatic degeneration. These results suggest that prothrombin time may be considered a valuable prognostic index. PMID- 2330586 TI - The role of metabolism and covalent binding in the cytotoxicity of a nitrogen containing steroid toward rat hepatocytes. AB - The nitrogen-containing steroid N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androst 1-ene-17 beta-carboxamide (I) causes concentration- and time-dependent cytotoxicity toward freshly isolated F-344 rat hepatocytes. Because hepatocytes extensively metabolize I to both stable and reactive products, the role of metabolism and covalent binding in the cytotoxicity of I was investigated. Concentration-dependent covalent binding of I-related material to hepatocyte macromolecules was detected. Treatment of rats with phenobarbital increased the rate and extent of hepatocyte metabolism of I, increased the covalent binding of I-related material to hepatocyte macromolecules, but decreased the cytotoxicity of I. Addition of testosterone to incubations of hepatocytes and I inhibited the metabolism of I, decreased the covalent binding of I-related material to hepatocyte macromolecules, but potentiated the cytotoxicity of I. These results indicate that the covalent binding of reactive metabolites is not involved in the cytotoxicity of I. Moreover, the two major metabolites of I, the 4-carbinolamide and monoethyl analog, were much less cytotoxic toward hepatocytes than I. These data suggest that the metabolism of I represents detoxication and that the parent compound is the cytotoxicant. PMID- 2330585 TI - Cyanide-induced neurotoxicity: calcium mediation of morphological changes in neuronal cells. AB - Calcium channel blockade decreases the elevation of brain calcium as well as the tremors produced by cyanide in mice. To determine if cyanide-induced morphological changes could also be inhibited by calcium channel blockade, the effect of diltiazem was studied in cultured rat pheochromocytoma (PC12) cells, a neuronal model. Incubation with KCN (1 to 10 mM for 1 to 2 hr) caused depletion of secretory granules, alignment of remaining granules along the plasma membrane, and mitochondrial swelling. All these effects were inhibited by pretreatment with 0.01 mM diltiazem. Scanning electron microscopy revealed that cyanide (1 to 10 mM for 1 to 2 hr) produced loss of microvilli and bleb formation in PC12 cells. These changes were partially inhibited by preincubation with 0.01 mM diltiazem. Incubation of cells with 10 mM cyanide increased release of lactic dehydrogenase (LDH) into the culture media at 60 and 120 min. A decrease in cell viability, as determined by trypan blue dye exclusion, paralleled the release of LDH. At 120 min of cyanide incubation, 24% of the cells excluded dye. Both the release of LDH and decreased cell viability were attenuated by pretreatment with diltiazem. The results indicate that the influx of extracellular calcium is an important factor mediating cyanide-induced morphologic changes in neuronal cells. PMID- 2330587 TI - Preliminary evidence for a cocaine-induced embryopathy in mice. AB - The current dramatic increase in illicit cocaine use by individuals during their reproductive years has heightened concerns over the possible adverse effects of maternal cocaine abuse during pregnancy. To address such concerns, the teratogenic effects of cocaine hydrochloride were investigated in two inbred mouse strains (SWV and DBA/2J). The drug was administered on either Gestational Days 6-8 or 8-10 by intraperitoneal injection, and the progeny examined on Gestational Day 18. While treatment with increasing concentrations of the drug did not adversely affect the rates of implantation, resorption, maternal weight gain, or fetal weights, there was a dose-related effect on the frequency of congenital malformations. This was consistently observed in both mouse strains. The types of congenital defects observed in the mouse fetuses bore a striking similarity to those reported in the clinical literature, including cardiovascular defects, limb abnormalities, and genitourinary malformations. PMID- 2330588 TI - Cross-tolerance to hyperoxia following cadmium aerosol pretreatment. AB - Preexposure of male Lewis rats to Cd aerosols (1.6 mg Cd/m3, 3 hr/day, 5 days/week, for 4 weeks) has been found to produce a marked degree of tolerance to hyperoxia (greater than 96% O2). Cd-pretreated animals were still alive after 8 days of continuous exposure to oxygen. In contrast, hyperoxia was fatal to all air-preexposed animals within 54-62 hr. Lungs of Cd-pretreated animals were characterized by hyperplasia and/or hypertrophy of the type II alveolar cell compartment which may have enabled them to more rapidly repair oxidant damage resulting from hyperoxia. Cd pretreatment augmented enzymatic antioxidant enzyme activities, including total lung Se-dependent glutathione peroxidase, catalase, glutathione reductase, and Mn-superoxide dismutase, and caused elevations in pulmonary nonprotein thiols and metallothionein (MT). MT, a thiol-rich, low molecular-weight protein, was 400-fold higher in Cd-pretreated animals and bound more than 80% of the total Cd in the lung. We have hypothesized that MT serves as an expendable yet renewable cellular target for free radical damage during oxygen exposure. A systemic acute-phase response, characterized by alterations in plasma Zn and Cu concentrations and increased ceruloplasmin oxidase activity, was initiated in Cd-pretreated animals by the fourth day of hyperoxia. This response was accompanied by improvement in pulmonary status and extensive pulmonary repair. PMID- 2330589 TI - Lead inhibits the basal and stimulated responses of a rat osteoblast-like cell line ROS 17/2.8 to 1 alpha,25-dihydroxyvitamin D3 and IGF-I. AB - Low-level exposure to lead impairs longitudinal growth in children and in experimental animals. The proposed mechanisms include decreased osteocalcin secretion in response to 1 alpha,25-(OH)2 vitamin D3 and decreased response to insulin-like growth factor-I. The interaction of lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I was investigated in an osteoblast-like cell line from rat osteosarcoma, ROS 17/2.8. Cells were cultured 24 hr in a serum-free medium with lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I. 1 alpha,25-(OH)2 vitamin D3 (10 nM) evoked a 4-5 X increase in osteocalcin secretion and a 100% increase in cellular alkaline phosphatase activity but no increase in DNA/cell layer. Insulin-like growth factor-I (92.5 ng/ml) evoked a 100% increase of osteocalcin secretion and a 20% increase in cellular DNA contents but no change in cellular alkaline phosphatase activity. Basal and stimulated cellular osteocalcin secretion, cellular alkaline phosphatase activity, and DNA contents were significantly inhibited by addition of 1-10 microM lead. The data are consistent with a toxic effect of lead on osteoblastic function and the cellular responses to 1 alpha,25-(OH)2 vitamin D3 and insulin like growth factor-I. This interaction may be relevant to impaired childhood growth at low levels of lead exposure. PMID- 2330590 TI - Allylamine and beta-aminopropionitrile-induced vascular injury: an in vivo and in vitro study. AB - Toxic cardiovascular effects of allylamine and beta-aminopropionitrile were studied in adult male Sprague-Dawley rats given allylamine alone (AA), 100 mg/kg/day, beta-aminopropionitrile alone (beta APN), 1 g/kg/day, or both chemicals (AA + beta APN) by gavage. Rats were given a total of 10 doses in 11 days. Rats given AA + beta APN showed extensive smooth muscle cell necrosis of the aortic media not seen when either toxin was given alone. Lingual artery lesions in the form of small intracellular eosinophilic globules were seen in animals given AA and AA + beta APN treatments, but were more numerous and larger in the latter group by morphometric analysis (p less than 0.03). Myocardial necrosis was much less severe in the AA + beta APN treatment group than in rats given only AA. A long-term follow-up (47 and 180 days) after the AA + beta APN protocol above showed that rats had persistent aortic medial necrosis with striking intimal cartilaginous metaplasia. Cultured porcine aortic smooth muscle cells exposed in vitro to combined AA and beta APN showed markedly decreased viability and increased cell injury when compared to cells exposed to only one toxin, thus supporting the synergistic toxic effect seen in vivo. Our studies show a synergistic necrotizing effect of AA and beta APN on aortic vascular smooth muscle cells. A hypothesis concerning these compounds' effects on vascular amine oxidases is made to explain this toxic synergism. Synergistic toxic interactions may be important in other forms of vascular injury. PMID- 2330591 TI - Localization of mercury in CNS of the rat. II. Intraperitoneal injection of methylmercuric chloride (CH3HgCl) and mercuric chloride (HgCl2). AB - The autometallographic method has been used to determine the precise localization of mercury in the brain and spinal cord of adult Wistar rats which had been treated with repeated ip injections of methylmercuric chloride (CH3HgCl; 0.2 to 10.0 mg) or mercuric chloride (HgCl2; 0.2 to 10.0 mg). The distribution of mercury was uneven following administration of HgCl2, while it was fairly homogeneous following CH3HgCl. With both compounds, however, heavy deposits of mercury were present in the motor nuclei of rhombencephalon. In contrast, cerebellar Purkinje cells, Golgi cells, and Golgi epithelial cells only contained mercury in sections from rats exposed to CH3HgCl. In cerebral sections from rats exposed to CH3HgCl, staining intensity in cortical cells varied among the layers, being greatest in laminae III, V, and VI. On the other hand, sections from rats exposed to HgCl2 showed only staining in scattered cells of lamina VI. Following administration of either compound, mercury was detected in the gray matter of the spinal cord mercury. Particularly large deposits were present in the anterior horn motoneurons. At the cellular level, the heaviest staining intensity was seen in neurons, although the cytoplasm of glia and ependymal cells also showed significant deposits in sections from rats exposed to CH3HgCl. In HgCl2-treated rats, the largest accumulations of mercury were seen in the neurons. The ependymal cells were stained to a lesser extent, while glia were devoid of mercury. Ultrastructurally, mercury deposits were located exclusively in lysosomes. The present results demonstrate that the pattern of mercury distribution and its staining intensity in individual cells in the rat CNS are dependent upon the chemical structure of the compound and the duration of its administration. PMID- 2330592 TI - Structure-activity relationships of retinoids in developmental toxicology. IV. Planar Cisoid conformational restriction. AB - To evaluate the influence of the three-dimensional configuration of retinoids on teratogenic activity, 14 retinoids were studied in hamsters. Retinoids with a conformational restriction of the retinoic acid polyene chain adjacent to the beta-cyclogeranylidene ring showed increased teratogenic potency and retinoids with aromatic conformational restriction adjacent to the polar terminus showed potency equivalent to retinoic acid. Conformational restriction of the polyene chain that permits rotation of the bond adjacent to the beta-cyclogeranylidene ring abolished teratogenic activity. Incorporation of dimethyl substituents at positions corresponding to C1 and C4 positions of retinoic acid enhanced teratogenic potency. Elimination of the twist chair conformation of gem-dimethyl substituents via incorporation of a benzothiopyran or substituted planar aromatic ring decreased teratogenic potency. Planar cisoid conformational restriction alone was insufficient to confer teratogenic activity in that elimination of the polar terminus abolished teratogenic activity. That an acidic polar terminus, as contrasted to a carboxyl residue per se, was required for teratogenic activity was illustrated by administration of a retinoidal phenyl sulfone which was metabolized to the corresponding teratogenic sulfonic acid. Retinoid teratogenicity in hamsters depends upon the assumption of a 10,11 cisoid and/or 12,13 cisoid rotameric form by a conjugated spacer greater than five carbon atoms in length located between a hydrophobic ring system and an acidic terminus, ionized at physiologic pH. Comparison of the relative teratogenic potencies of this series of conformationally restricted retinoids with their activities in assays for chemoprevention activity showed that those analogs with high intrinsic control of epithelial or mesenchymal cell differentiation were also the more potent teratogens. The results suggest that those biochemical mechanisms responsible for retinoid control of normal adult or neoplastic cell differentiation also mediate retinoid-induced teratogenesis. PMID- 2330593 TI - Subacute nephrotoxicity of germanium dioxide in the experimental animal. AB - Germanium (Ge; atomic number 32, atomic weight 72.6) belongs to IVb group of the Periodic Table and is found as a trace metal in soil, rocks, plants, and animals. It is widely used in industry because of its semiconductive nature. Some biological activities have been shown in Ge derivatives. Recently, patients with persistent renal damage after chronic ingestion of germanium dioxide (GeO2) containing compounds have been reported in Japan. This study aimed to investigate subacute nephrotoxicity of GeO2 in Lewis male rats. The rats were treated orally with GeO2 for 13 weeks (GeO2 group) and were compared with those treated with GeO2 for only the first 4 weeks (GeO2-4-week group) and with untreated controls. Renal dysfunction was demonstrated by the increased serum creatinine, BUN, and serum phosphate and decreased creatinine clearance. Liver dysfunction was observed as demonstrated by the increased GOT and GPT, and hypoproteinemia by the decreased total protein and albumin in the GeO2 group. However, daily urinary protein excretion or urinalysis did not differ among the groups. Kidney weight and Ge content of tissues were significantly elevated in the GeO2 group. With the light microscope, vacuoles and the depositions of PAS-stained particles, which correspond to electron-microscopic dense granules in the swollen mitochondria, were predominantly observed in distal tubular epithelium in the GeO2 group. Even in the GeO2-4-week group of rats, serum creatinine was increased and the above mentioned histological abnormalities were observed, but were less intense. PMID- 2330594 TI - Lack of sensitive period for lead-induced behavioral impairment on a spatial delayed alternation task in monkeys. AB - A total of 52 monkeys (Macaca fascicularis) were dosed orally with vehicle or 1.5 mg/kg/day of lead on one of four dosing regimens (13 monkeys/group): vehicle only; dosed with lead from birth onward; dosed with lead from birth to 400 days of age and vehicle thereafter; dosed with vehicle from birth to 300 days of age and lead thereafter. Blood lead concentrations averaged 3-6 micrograms/dl when monkeys were not being dosed with lead, 32-36 micrograms/dl when being dosed with lead and having access to infant formula, and 19-26 micrograms/dl when being dosed with lead after weaning from infant formula. When monkeys were 6-7 years old, they were tested on a spatial delayed alternation task. The task required the monkey to alternate responses between two push buttons. The initial delay was 0.10 sec and was increased in steps to 15 sec by the end of the experiment. All three treated groups were impaired to approximately an equal degree. Deficits were observed in the initial training procedure, and at the longer delay values. These results suggest that there is not an early critical period for lead-induced impairment on this task and that exposure only during infancy results in impairment comparable to ongoing exposure beginning at birth. These results are in contrast to previous findings on a series of nonspatial discrimination reversal tasks, in which the group exposed early in life only was unimpaired, while the group exposed beginning after infancy was less impaired that the group exposed continuously from birth. PMID- 2330595 TI - Protection against cyanide-induced convulsions with alpha-ketoglutarate. AB - Protection against convulsions induced by cyanide was observed after treatment with alpha-ketoglutarate, either alone or in combination with sodium thiosulfate, a classical antagonist for cyanide intoxication. However, sodium thiosulfate alone did not protect against cyanide (30 mg/kg)-induced convulsions. gamma Aminobutyric acid (GABA) levels in brain were decreased by 31% in KCN-treated mice exhibiting convulsions. The combined administration of alpha-ketoglutarate and sodium thiosulfate completely abolished the decrease of GABA levels induced by cyanide. Furthermore, sodium thiosulfate alone also completely abolished the decrease of GABA levels. These results suggest that the depletion of brain GABA levels may not directly contribute to the development of convulsions induced by cyanide. On the other hand, cyanide increased calcium levels by 32% in brain crude mitochondrial fractions in mice with convulsions. The increased calcium levels were completely abolished by the combined administration of alpha ketoglutarate and sodium thiosulfate, but not affected by sodium thiosulfate alone. These findings support the hypothesis proposed by Johnson et al. (Toxicol. Appl. Pharmacol., 84 (1986) 464) and Robinson et al. (Toxicology, 35 (1985) 59) that calcium may play an important role in mediating cyanide neurotoxicity. PMID- 2330596 TI - Effects of an organic hydroperoxide on the activity of antioxidant enzymes in cultured mammalian cells. AB - As a basis for an evaluation of the role of the cellular antioxidant defense system against oxidative stress, the effects of an organic hydroperoxide, tertiary-butyl hydroperoxide (t-BuOOH), on the activity of antioxidant enzymes were investigated in cultured Chinese hamster V79 cells. Incubation of cells with t-BuOOH for 1 h significantly increased the activity of Cu-Zn superoxide dismutase (SOD) up to a level 1.4 times that of control cells. In contrast, the activities of catalase and glutathione reductase (GSSG-Rx) were not affected, while the activity of glutathione peroxidase (GSH-Px) was inhibited to a significant extent by t-BuOOH. Hydrogen peroxide also inhibited GSH-Px activity but its potency in this regard was somewhat lower than that of equimolar amount of t-BuOOH. Earlier studies demonstrated that t-BuOOH-induced cytotoxicity, single strand breaks (ssb) in DNA and structural aberrations in the chromosomes of V79 cells can be suppressed almost completely by an iron chelator o phenanthroline. However, the iron chelator did not suppress the t-BuOOH-induced inhibition of GSH-Px activity. Likewise, a diffusible scavenger of free radicals, butylated hydroxytoluene (BHT) did not affect the hydroperoxide-induced inhibition of the enzymatic activity. These results suggest that a mechanism other than iron-mediated radical reaction is involved in the inhibition of GSH-Px activity by t-BuOOH. Modulation of the activity of antioxidant enzymes by the oxidative agent diamide was very similar to that by t-BuOOH. Inhibition of GSH-Px activity by t-BuOOH was reversible and the reduced activity returned to pre inhibition levels within 1-2 h of post-treatment incubation. A mechanism for the inhibition of GSH-Px by t-BuOOH is discussed with reference to the oxidation of selenocysteine residues which results in perturbation of the normal catalytic cycle. PMID- 2330597 TI - Brain phenylalanine and tyrosine levels and hepatic encephalopathy induced by CCl4 in rats. AB - The correlation between the levels of brain aromatic amino acids and hepatic encephalopathy induced by CCl4 was investigated in rats. CCl4 (1.0 ml/kg three times per week for over 10 weeks) caused hyperammonemia and hepatic encephalopathy in rats. The brain levels of aromatic amino acids, especially tyrosine (Tyr) and phenylalanine (Phe) in rats with hepatic encephalopathy were increased by 605% and 255% respectively from that of the corresponding controls. Furthermore, a single intraperitoneal injection of 2,4-dinitrophenol (DNP; 30 mg/kg) in CCl4-treated rats (1.0 ml/kg three times per week for 7 weeks) showed hyperammonemia and hepatic encephalopathy (loss of consciousness) elicited a marked increase of Tyr and Phe levels in the brain. In addition, the blood levels of Tyr and Phe in all rats with hepatic encephalopathy were greatly elevated as compared to controls. On the other hand, continuous injection of ammonium chloride (20 mg N/ml) into the jugular vein for 1 h caused severe hyperammonemia without loss of consciousness. The brain levels of Tyr and Phe showed no change from the corresponding controls. These results suggest that the increase of aromatic amino acids, such as Tyr and Phe, in brain produced by hyperammonemia and high blood levels of Tyr and Phe may be a critical event to the development of hepatic encephalopathy. PMID- 2330598 TI - Induction of rat liver microsomal cytochrome P-450 by the pentabromo diphenyl ether Bromkal 70 and half-lives of its components in the adipose tissue. AB - Pentabromo diphenyl ether (Bromkal 70) was investigated for its half-life in perirenal fat of male and female Wistar rats following a single 300 mg/kg p.o. dose. Half-lives of five individual component fractions following extraction and separation with HPLC were between 30 and 91 days in female rats and between 19 and 119 days in male rats. Induction experiments in male and female Wistar rats with long-term (50 mg/kg daily for 28 days) and short-term administration (300 mg/kg once or 100 mg/kg daily for 4 days) resulted in a 2.3-3.9-fold increase of the cytochrome P-450c, an up to 2-fold increase of benzphetamine N-demethylation activity, a 2.2-5.3-fold increase of the benzo[a]pyrene oxidation activity, and an increase of the ethoxyresorufin O-deethylation activity to between 4.1 and 16.6 nmol/min mg microsomal protein. All variations of enzymatic activities were dependent on the animals' sex or on the administration schedule of the pentabromo diphenyl ether. The threshold for induction of the ethoxyresorufin O-deethylation or benzo[a]pyrene oxidation was between 3 and 10 mg/kg. In conclusion, with regard to the induction of cytochrome P-450 types pentabrominated diphenyl ethers behave as mixed-type inducers. PMID- 2330599 TI - The effect of cadmium and other metals on vascular smooth muscle of the dogfish shark, Squalus acanthias. AB - The effect of Cd2+ and related metals (Ni2+, Hg2+, Pb2+, Co2+, Sn2+ Cu2+ and Zn2+) on vascular tension was studied using isolated rings of endothelium-free, smooth muscle from the ventral aorta of the shark, Squalus acanthias. Both Cd2+ and Ni2+ produced significant vasoconstriction at concentrations at or above 10( 6) M (112 and 59 ppb, respectively); the other metals were either marginally constrictive (Hg2+ and Sn2+) or were without effect (Pb2+, Co2+, Cu2+, and Zn2+). We suggest that previously published vascular effects of Hg2+ and Pb2+ may have been secondary to responses of the vascular endothelium, and that the role of Ni2+ in hypertension should be investigated further. Our data indicate that the effects of metals on this vascular smooth muscle are specific and not generic. Moreover, this system could be utilized to investigate the mechanisms of metal induced vasoconstriction. PMID- 2330600 TI - Quantitation of blood plasma DNA as an index of in vivo cytotoxicity. AB - Cell death triggers the release into extracellular spaces of products of chromatin catabolism, particularly of DNA. A sensitive DNA assay has been used to investigate in the mouse whether the quantitation of plasma DNA may be used as an index of in vivo cytotoxicity. It has been found that toxic doses of bacterial lipopolysaccharide, HgCl2, CCl4, cyclophosphamide and hydroxyurea, are responsible for the release of extracellular DNA in plasma, in a dose dependent relationship. In conclusion, quantitation of extracellular DNA may be used for investigating in vivo cell death phenomena induced by toxic agents and drugs. Such a method could be applied to toxicological studies in animals and man. PMID- 2330601 TI - Effect of storage temperature on the stability of the liquid polyvalent antivenom produced in Costa Rica. AB - The effect of storage temperature on the stability of the liquid polyvalent (crotaline) antivenom produced at the Instituto Clodomiro Picado, Costa Rica, was studied during a twelve-month period. The following parameters were evaluated: neutralizing potency against lethal activity of Bothrops asper venom; protein and phenol concentrations; pH; turbidity; safety; and sterility. Analyses were performed each month on different samples of a batch, stored at 4, 23, 30 and 37 degrees C. No significant (P greater than 0.1) variations occurred in potency, protein and phenol concentrations, pH, sterility or safety, at any of the storage temperatures during the study period. However, visual inspection revealed a moderate increase in turbidity of the samples stored at 23, 30 and 37 degrees C, at nine, four and three months, respectively. Culture of samples excluded the possibility of microbial contamination of the product leading to turbidity. Chromatographic and electrophoretic analyses demonstrated that turbidity was caused by the formation of heterogeneous protein aggregates of high molecular weight. Present results support the conclusion that, although storage temperature (up to 37 degrees C for twelve months) does not alter antivenom potency, it significantly influences the formation of protein aggregates. This phenomenon can be prevented by recommending the storage of antivenom at refrigeration temperature. PMID- 2330602 TI - Nucleotide sequence and structure analysis of cDNAs encoding short-chain neurotoxins from venom glands of a sea snake (Aipysurus laevis). AB - Two cDNAs from the sea snake Aipysurus laevis have been cloned and sequenced. They encode isoforms of short chain neurotoxins. One of them is toxin b, previously isolated from the venom of Aipysurus laevis and sequenced by Maeda and Tamiya (Biochem. J. 153, 79, 1976), whereas the other corresponds to an isoform which was not hitherto described. The two toxin sequences differ from each other by three amino-acid residues. Both cDNA structures were comparable with that previously determined in our laboratory for erabutoxin a from Laticauda semifasciata. PMID- 2330603 TI - Occurrence of tetrodotoxin in the gastropod mollusk Natica lineata (lined moon shell). AB - Paralytic toxicity was detected in 28 of 38 specimens of the gastropod mollusk Natica lineata (lined moon shell). The highest toxicity, expressed as tetrodotoxin (TTX), was 720 mouse units per gram (MU/g) muscle, followed by other parts which included salivary gland, brain and mouth organs (28 MU/g) and digestive gland (12 MU/g). The toxin was partially purified by ultrafiltration and Bio-Gel P-2 column chromatography. The toxin showed a specific toxicity (as TTX) of 620 MU/mg. Results of analyses by thin layer chromatography, cellulose acetate membrane electrophoresis and high performance liquid chromatography showed that the toxin was composed of TTX and anhydrotetrodotoxin. This is the first time that TTX and its related substance have been found in this species of gastropod. PMID- 2330604 TI - Purification and amino acid sequence of basic protein I, a lysine-49 phospholipase A2 with low activity, from the venom of Trimeresurus flavoviridis (Habu snake). AB - A basic protein (pI 10.2), named basic protein I, was purified to homogeneity from the venom of Trimeresurus flavoviridis (Habu snake) after four chromatographic steps. The amino acid sequence of this protein was determined by sequencing the S-pyridylethylated derivative of the protein and its peptides produced by chemical (cyanogen bromide and formic acid) and enzymatic (chymotrypsin, Achromobacter protease I, and Staphylococcus aureus V8 protease) cleavages. The protein consisted of 122 amino acid residues and was similar in sequence to phospholipases A2 from the venoms of crotalid and viperid snakes. A most striking feature of this protein is that aspartic acid at the 49th position common in phospholipases A2 is replaced by lysine. When the protein acted on 1 palmitoyl-2-oleoyl-sn-glycero-3-phosphorylcholine, oleic acid was preferentially released, indicating that the protein has phospholipase A2 activity. Its molar activity toward 1,2-dilauroyl-sn-glycero-3-phosphorylcholine, however, was 1.5% that of T. flavoviridis phospholipase A2 isolated previously. The fact that both affinity to Ca2+ and reactivity to p-bromophenacyl bromide of basic protein I are approximately one order of magnitude lower than those of T. flavoviridis phospholipase A2 might explain the low activity of basic protein I. PMID- 2330605 TI - Effect of phoratoxin B, a toxin isolated from mistletoe, on frog skeletal muscle fibres. AB - The effect of phoratoxin B on transmembrane potentials and currents of frog skeletal muscle was studied using intracellular microelectrode recording and double sucrose gap voltage clamp techniques. Phoratoxin B irreversibly depolarized the membrane. The depolarization was insensitive to tetrodotoxin, tetraethylammonium, 4-amino-pyridine, cesium, cadmium and D-600. In voltage clamp experiments, phoratoxin B induced an inward resting current (Irest) which did not inactivate. Irest was blocked by increasing the external calcium concentration in the Ringer solution; it was not blocked when Sr2+ replaced Ca2+. Analysis of the peak sodium current indicated that while both Ca2+ and Sr2+ screen membrane surface charges, Ca2+ bound and reversed the phoratoxin B induced Irest whereas Sr2+ did not. The inward Irest induced by phoratoxin B developed in the presence of external chloride and remained unchanged in the presence of bicarbonate. The data suggest that the depolarizing action of the toxin might be attributed to an increase in the non-selective leak current and that it might act as a detergent. PMID- 2330606 TI - Effects of aluminum on brain lipid peroxidation. AB - Excessive dietary aluminum (Al) has been proposed to be a factor contributing to several neurological disorders in humans. Six 8-week-old female Swiss Webster mice were fed for 10 weeks purified diets containing 100 (control, 100 Al), 500 (500 Al) or 1000 (1000 Al) micrograms Al/g diet. Brain and liver lipid peroxidation was determined by evaluating the production of 2-thiobarbituric acid reactive substances (TBARS) in brain and liver homogenates in the presence or absence of 50 microM ferrous iron. TBARS production in the absence of iron in brain homogenates from mice fed the 1000 Al diet was higher (30%) than that in the 100 Al control group (3.1 vs. 2.4 nmol TBARS/mg protein). The addition of ferrous iron increased TBARS production in brain homogenates from all 3 dietary groups. The iron-induced TBARS production was 26% higher in the 1000 Al brain homogenates than in the 100 Al group (4.9 vs. 3.9 nmol TBARS/mg protein). Brain TBARS production in the presence and absence of iron was similar between the 100 and 500 Al groups. TBARS production in liver homogenates measured either with or without iron was similar for the 3 groups. These results show that, in mice, dietary Al intoxication leads to increased brain TBARS production, suggesting that enhanced lipid peroxidation may be one possible mechanism underlying the neurological damage associated with increased tissue Al. PMID- 2330607 TI - Sequence of cardiorespiratory effects of soman altered by route of administration. AB - Dilute soman was administered to anesthetized guinea-pigs by slow infusion (30 micrograms/kg/10 min); intravenous (IV), subcutaneous (SC), intraperitoneal (IP), intratracheal (IT), and upper-airway (UAW) routes were used. Times to ventilatory failure were 8.8 +/- 1.3 min (IV), 10.5 +/- 1.2 min (I.T.), 17.3 +/- 2.8 min (IP), 34.8 +/- 5.1 min (UAW), and 36.0 +/- 4.4 min (SC) for the 5 routes of exposure. Atrioventricular (AV) block occurred before ventilatory failure with all routes of challenge except IT and IP; when it did occur, AV block typically began after one-half reduction in minute volume. The results reflect the effects of rate of absorption and noncritical-site binding of the organophosphorus compound when all routes are compared and suggest that the pathogenesis of intoxication in the anesthetized guinea-pig is different when soman is infused into regions heavily enervated by vagal afferents. PMID- 2330608 TI - Descriptive epidemiology of adenocarcinomas of the cardia and distal stomach in the Swiss Canton of Vaud. AB - Incidence registration and survival data from various anatomical subsites of gastric cancer have been abstracted from the population-based Cancer Registry of the Swiss Canton of Vaud for the period 1976-87. Overall age-standardized (Vaud population in 1980) incidence rates for all gastric adenocarcinomas were 22.2/100,000 males and 8.3/100,000 females, with a sex ratio of 2.7. The male preponderance was appreciably greater for cardia (5.9 vs 0.9, sex ratio = 6.5) than for distal stomach (10.2 vs 5.0, sex ratio = 2.0). Adenocarcinomas of unspecified origin had an intermediate sex ratio (2.6). The sex ratio for all gastric adenocarcinomas was lower in the third and fourth decades of age (1.3) than at older ages. In relation to calendar period of diagnosis, no appreciable trend with time was observed for adenocarcinomas of the cardia, and only some modest decline was observed for distal stomach, in the presence of stable sex ratios. A marked fall was observed for "other and unspecified" subsites. Thus, the overall decline in the incidence of gastric adenocarcinomas over the calendar period considered was about 20% for males and 30% for females. Five-year survival was significantly higher for cancers arising in the distal stomach (30%) than for cardiac carcinomas (11%), and intermediate for "other and unspecified sites" (19%). These results indicate that adenocarcinomas arising from the cardia and those arising from the distal stomach are considerably heterogeneous in relation to descriptive epidemiology and prognosis. This may have relevant etiological correlates, particularly since carcinoma of the cardia appears to share important epidemiologic features with esophageal cancer. PMID- 2330609 TI - Morphological heterogeneity and phenotype modifications during long term in vitro cultures of six new human glioblastoma cell lines. AB - Long term in vitro cultures of six human malignant gliomas were established to obtain permanent lines and to assess, under conditions of prolonged culture, changes in morphology and phenotype of neoplastic cells and the extent of these modifications. We analyzed expression of the following markers by immunocytochemistry: glioma-specific antigens (GE2 and CG12), fibronectin, intermediate filaments (GFAP, vimentin, neurofilaments), class I and II histocompatibility antigens (HLA-ABC and HLA-DR), growth factor and receptor (alpha TGF and EGF-receptor), proliferation-associated antigen (Ki-67). Strong and stable staining with the two antiglioma monoclonal antibodies (GE2 and CG12) was seen, with coexpression of GFAP and fibronectin in five of six cell lines (after 20 passages) and presence of vimentin and neurofilaments. HLA-DR expression was heterogeneous, with a peculiar intracellular compartmentation in four of six cell lines. Cells showed clear cytoplasmic positivity for alpha TGF and strong membrane staining for EGF-receptor. In previous studies we showed that these cell lines have increased copies of chromosome 7; therefore we speculate that an autocrine pathway of stimulation may maintain the neoplastic growth. The percentage of Ki-67 positive proliferating cells ranged from 40 to greater than 60%, depending on cell line and passage. A slight decrease in the positivity of some markers (GFAP, vimentin and HLA-DR in 2/6 cell lines) was observed after prolonged in vitro culture (greater than 12 months), but morphophenotypic modifications, established within a few passages after explanation, were maintained with time. A clonogenic assay showed values of plating efficiency (PE) higher than corresponding values of other similar cell lines with a tendency to increase in the late passages. PE and Ki-67 positivity were not associated with tumorigenicity into nude mice (except the Hu 197 cell line). These results indicate that, in culture, all six cell lines acquired stable morphology, a well defined antigenic phenotype and high growth rate. Further studies will be performed on these permanent cell lines to clarify differentiation steps of malignant gliomas. PMID- 2330610 TI - Acute non lymphoid leukemia following CMF treatment as adjuvant therapy in positive node breast cancer. Case report. AB - The CMF regimen as an adjuvant therapy for breast cancer with axillary node involvement has become "standard therapy" at least for some subsets of patients (according to the Second Consensus Development Conference on Adjuvant Chemotherapy for Breast Cancer). The acute toxicity of such a regimen is usually mild and well tolerated; the late toxicity is mainly represented by amenorrhea. Here a case of acute non-lymphoid-leukemia (ANLL) after six CMF cycles is reported. PMID- 2330611 TI - Trends in patterns of care for breast cancer in Italy (1979-1987). AB - We reviewed care delivered to about 2,500 breast cancer patients in general hospitals over the period 1979-1987 using data from three surveys. The most important and consistent failure was in diagnostic timeliness: about one out of four patients was diagnosed six or more months after the first symptom leading to an almost doubled probability of being diagnosed with more advanced disease. Acceptance of treatment recommendations seemed less satisfactory for surgery than for adjuvant treatments. Conservative surgery still appeared to have limited acceptance for patients with small primary tumor (21 and 23% in 1983 and 1987, respectively) although, starting 1983, there was a shift from the Halsted to the Patey type of radical mastectomy. Follow-up was routine in most node-negative patients and adjuvant chemotherapy was already well established treatment for most pre-menopausal node-positive women (64, 79 and 76% in 1979, 1983 and 1987, respectively). Some form of adjuvant treatment in post-menopausal node-positive women was already present in 1983 but became more widespread in 1987 (82%): this being mostly accounted for by the increase in the use of tamoxifen (delivered alone or in combination with chemotherapy to 53% of women). Overall, our results suggest that areas of care more dependent on organization or doctors' and patients' education (i.e. diagnostic timeliness and accessibility) are those where deficiencies seen to be least amenable to change in the absence of concerted intervention. Among more narrowly defined clinical issues, there appeared to be some dissonance between the rapid acceptance of adjuvant treatments and the still slow pace of acceptance of less aggressive procedures by surgeons. PMID- 2330612 TI - Cancer mortality in Italy. PMID- 2330613 TI - Cancer mortality in Italy: an overview of age-specific and age-standardised trends from 1955 to 1984. AB - Number of certified deaths, age-specific and age-standardised rates and percentages of all cancer deaths from 30 cancers or groups of cancers (plus total cancer mortality) for each five-year calendar period between 1955 and 1984 in Italy are presented in tabular form. From these data, three graphs are derived, including trends in age-standardised rates, age-specific rates centered on birth cohorts and maps plotted in different shades of grey to represent the surfaces defined by the matrix of various age-specific rates. These analyses quantified the rises in overall cancer mortality in males (from 137 to 192/100,000 world standard), chiefly due to increases in lung and other tobacco-related neoplasms. Overall cancer mortality was stable in females (around 100/100,000). Appreciable cohort effects were evident for tobacco related neoplasms, but also for other major cancer sites, such as intestines or breast, whose rates, after earlier rises, are now stable in earlier middle age. Since the early 1970's, cancer mortality rates have been declining in all age groups below 40 in males and below 55 in females. These declines reflect improvements in therapy for leukemias, lymphomas and germ cell tumors, and general improvements in food availability and storage, hygiene and early diagnosis, which have led to the declines in stomach and cervical cancer. Although moderate in absolute terms and smaller than in other western countries where tobacco-related neoplasms have also been falling in more recent cohorts, these declines are encouraging for the indication they provide on the most likely patterns over the next decades in the same and subsequent generations. PMID- 2330614 TI - [Course and prognosis of primary Gougerot Sjogren syndrome]. PMID- 2330615 TI - [Sphenoid sinusitis]. PMID- 2330616 TI - [Rheumatoid purpura nephropathy in children: a retrospective study of 26 cases]. PMID- 2330617 TI - [Biochemical balance in the differential diagnosis of ascites]. PMID- 2330618 TI - [Eosinophilic fasciitis (Shulman's syndrome): apropos of a case report]. PMID- 2330619 TI - Crohn's disease revealed by a pelvic femoral osteomyelitis: a case report. PMID- 2330620 TI - [Epidemiologic situation of broncho-pulmonary cancer in Tunisia in 1988]. PMID- 2330621 TI - [Obstructive anuria: a study of 13 cases]. PMID- 2330622 TI - [Surgery of esotropia using asymmetric archs]. PMID- 2330624 TI - [Salmonella epidemics--what can we learn?]. PMID- 2330623 TI - [Lupus nephropathy observed at an internal medicine service]. PMID- 2330625 TI - [Follow-up of spinal analgesia with somatosensory evoked potentials and biotesiometry]. AB - In order to estimate the possible neurotoxicity of spinal analgesia with bupivacaine (Marcain), a total of ten patients were examined neurologically prior to spinal analgesia and seven days afterwards with somatosensory evoked potentials (SEP) and biotesiometry. The objective neurological examination results and SEP were entirely unchanged. At control examination with biotesiometry, altered vibration sense bilaterally over the medial malleoli was found in one patient but not on the pulp of the great toe bilaterally. Alterations in vibration in this patient were within the intraindividual variation as described by Fagius & Wahren. The method of examination employed here has not previously been employed systematically for follow-up investigation or elucidation of neurological deficits following spinal analgesia. PMID- 2330626 TI - [Changes in the function of a psychiatric department during 1983-1988]. AB - From 18.4.1988 to 17.6.1988, 374 emergency referrals were registered and 495 other referrals to the psychiatric admission department, Frederiksberg Hospital. The two main reasons for the referrals, in both men and women, were alcoholism and/or psychosis. Compared to a similar study from the same period in 1983, the number of emergency referrals was stabilized while the number of other referrals increased by 63%. The majority of the 495 other referrals were chronic psychotic patients and/or addicts who were, as a rule, already under treatment in the day care hospital or out-patient clinic. Previously, part of this group of patients remained in state mental institutions for long periods. After the change to district psychiatric treatment, the admission department acts as a semi-acute asylum, since suitable resorts outside the psychiatric institution are not available. PMID- 2330627 TI - [Narcotic abuse in Jylland. A study based on narcotics and deaths of addicts examined at the Institute of Forensic Medicine, University of Aarhus during the period 1981-1988. 1. Narcotics]. AB - On the basis of analysis of 1,879 samples of narcotics confiscated in Jutland and Funen during the period 1981-1988, the individual types of drugs are described as regards occurrence and quality. Cannabis and heroin were found in the illegal market during the entire period. Amphetamine was rarely observed prior to 1985 but comprised half of the illegal drugs examined in 1988. Cocaine was encountered in only 1% of the samples. Designer drugs were not seen. Heroin occurred relatively most frequently in Aarhus, Odense and Esbjerg while amphetamine and cannabis were found in all parts of Jutland and Funen. The samples of heroin and amphetamine varied greatly as regards strength and the types and quantities of cutting agents. The majority of the samples were adulterated and/or diluted with substances such as caffeine and phenazone and the sugars, glucose and lactose. PMID- 2330628 TI - [Narcotic abuse in Jylland. A study based on narcotics and deaths of addicts examined at the Institute of Forensic Medicine, University of Aarhus during the period 1981-1988. 2. Deaths among addicts]. AB - A total of 229 deaths among drug addicts (194 men and 35 women) examined of the Institute of Forensic Medicine, University of Aarhus during the period 1981-1988 is described. In 178 deaths, the cause of death was poisoning with a drug or illegal narcotic. Alcohol was involved in nearly half of these deaths and was, in addition, the cause of death in 4% of the cases. Heroin or morphine were the causes of death in one third of the cases while detropropoxyphene, methadone and ketobemidone were responsible for approximately half of the deaths. Until 1986, dextropropoxyphene was the dominating drug whereas the number of methadone deaths was considerably greater in the latter half of the period investigated than in the first half. Amphetamine alone was rarely the cause of death but the drug was seen in an increasing number of deaths in recent years. Thus, amphetamine was found in one third of the deaths in 1988. PMID- 2330629 TI - [Telephone consultations with the pediatrician on-call]. AB - Prospective registration of telephone consultations with the paediatrician-on call during a period of four months was undertaken. Telephone records were made for this purpose and 256 consultations were registered. In 39% of these consultations, the contact was with a doctor who desired advice about a definite patient. In 36%, the persons making the contact were parents of children attending the paediatric outpatient clinic. 20% of the contacts were from parents of acutely ill children and were without connection with the paediatric department. In 37% of the consultations therapeutic advice was given. The paediatrician-on-call appears to have a function as an emergency telephonic consultant for the primary and secondary health sectors and as the doctor-on call. Establishing of telephone records in paediatric departments is recommended. PMID- 2330630 TI - [Lowest heart rate and pauses in adults with healthy hearts]. AB - The lowest heart rate measured in a one minute period (HRmin) and prevalence of pauses, was determined with eight years interval, in two 24 hour Holter Monitorings, in 183 persistently healthy adults aged 40 to 85 years. For the individual, HRmin is a stable parameter, but the level depends on sex, smoking and physical activity habits. Independently of age, HRmin less than 40 beats per minute and pauses greater than or equal to 2.0 seconds are rare events, and should be considered abnormal. PMID- 2330631 TI - [Complications after osteosynthesis using Partridge's method in femoral fracture near the prosthesis]. AB - The object of the investigation is to illustrate the results and complications following Partridge's osteosynthesis of proximal fractures in the neighbourhood of the prosthesis. During a period of 40 months, eight consecutive patients (two men and six women) with proximal fractures of the femur in the neighbourhood of a hip prosthesis were subjected to osteosynthesis by Partridge's method. All of the fractures resulted from low energy trauma. The average age was 72 years (51-84) and the average duration of observation was 2.3 years. Weight-bearing was permitted after an average of 14.5 weeks and the radiographically assessed healing time was 16 weeks on an average. In all of the patients, cortical erosion developed under the Partridge bands 10-16 weeks postoperatively. In five patients, the initial erosions were of limited extent and were stationary during the period of observation. In three patients, the osteolysis was progressive and reoperation with introduction of a long-shafted femur prosthesis proved necessary. In addition, homologous boney transplants were necessary in two of these patients. Stability and healing of the fracture are obtained by osteosynthesis by Partridge's method but, on account of the osteolysis which is frequently pronounced and progressive, the patients should be followed-up meticulously in view of the possibility of removal of the Partridge material and possible replacement by a long-shafted femur prosthesis before the bone is completely eroded. PMID- 2330632 TI - [Osteochondritis dissecans of the calcaneus]. AB - We report a case of osteochondritis dissecans located to the posterior calcanear articular surface of the talocalcaneal joint. The lesion was diagnosed by radiological tomography of the joint. The treatment was surgical excision of the affected segment. The patient was still symptomfree three years later. PMID- 2330633 TI - [Poisoning with nightshade, Atropa belladonna]. AB - Serious poisoning with atropine-like substances may produce symptoms which can be confused with acute psychosis. The diagnosis in a case of acute poisoning may be difficult and diagnostic treatment with physostigmine may be considered. A case of serious atropine poisoning caused by consumption of the fruits of deadly nightshade (Atropa belladonna) which commenced with psychosis in a boy of nine years is described. It was known that the child had eaten 20-25 of the berries. He survived after treatment with intravenous administration of physostigmine. PMID- 2330634 TI - [Basocellular carcinoma of the skin with metastases to lymph glands and the parotid]. AB - Metastases from basocellular carcinomata in the skin are extremely rare. A case of recurrent basocellular in the skin with regional lymph gland metastases and metastases to the parotid gland is presented. The clinically common features in metastasizing basocellular carcinoma are emphasized. PMID- 2330635 TI - [Intra-atrial ECG]. PMID- 2330637 TI - [Ice--a new designer drug]. PMID- 2330636 TI - [Diagnosis of primary intracranial meningioma--the informative value of diagnostic tests]. PMID- 2330638 TI - [New knowledge on the pathogenesis of multiple sclerosis]. PMID- 2330639 TI - [Diaphragm pacing by electric stimulation of the phrenic nerves]. AB - Artificial ventilation by electric stimulation of the phrenic nerves has become clinically significant within the past 20 years and, in the world as a whole, approximately 700 patients have been treated with implanted diaphragmatic pacemakers. The two first patients in whom diaphragmatic pacemakers were implanted in Denmark, had sustained accidental fractures of the second cervical vertebra with subsequent high cervical spinal cord lesions with not only tetraplegia but also respiratory arrest. In both patients, diaphragmatic pacemakers were implanted bilaterally and these were employed for 12-14 hours daily while ventilation with a respirator was employed at night. The main indications for diaphragmatic pacing are paralysis of respiration following high cervical spinal traumata and the chronic central hypoventilation syndrome (sleep apnoea of Undine's curse). Diaphragmatic pacing may improve the mode of ventilation and the quality of life for patients with tetraplegia and respiratory insufficiency. On account of the potential technical problems, the risk of complications and the limited number of patients in whom this operation is suitable, implantation of diaphragmatic pacemakers should be concentrated in a few centres and probably only one in Denmark. PMID- 2330640 TI - [Seasonal variation in disseminated sclerosis]. AB - Forty-five patients with clinically definite multiple sclerosis (DS) with onset in the period studied, were reviewed retrospectively. The time of the first exacerbation after the onset, but not the time of onset exhibited seasonal variation (p = 0.003), as 76% of the exacerbations occurred in the winter months. On review of all 148 cases of clinically definite DS in the department's records, a seasonal variation was found of both the time of onset (p = 0.047) and the time of the next exacerbation (p = 0.0004). In previous studies different seasons of peak disease activity were found. These differences may be caused by different methods or by differences in the local factors, which influence the course of the disease. The seasonal variation of the frequency of the disease manifestations is probably caused by a variation in environmental factors. In this study, the importance of infections could not be evaluated. PMID- 2330641 TI - [Models for calculating risks as a tool in screening for cardiovascular diseases]. AB - In connection with screening for risk factors for ischaemic heart disease in Bispebjerg Hospital, we have assessed three different models for calculation of the risk, employed on our own material. A total of 462 persons participated in the screening and 275 of these were under the age of 65 years. Out of these 275, 92 had plasma cholesterol values over or equal to 7.0 mmol/l and or smoked over 20 gram tobacco daily. On comparison between three models for calculation of the risk: one American, one British and one Swedish, moderate agreement was observed: the correlation coefficients varied between 0.75 and 0.89. The reason for this may be that the models for calculation of the risk are constructed on the basis of statistics already described from epidemiological investigations in which coincidence is demonstrated between selected observable factors and ischaemic heart disease. It is thus possible that the factors which we measure and possibly attempt to influence are not pathogenetic. We consider, therefore, that risk scoring should be employed with caution. As causal connection between ischaemic heart disease and cholesterol and smoking, respectively, have been demonstrated with reasonable certainty, we consider that it is reasonable to screen and intervene for these factors alone. PMID- 2330642 TI - [Frequency of causes of death related to sudden infant death syndrome in Denmark during the period 1972-1983]. AB - Differences in the incidence of infant mortality due to sudden infant death syndrome between the regions of the three Institutes of Forensic Medicine in Denmark are known to exist. To investigate whether these could be due to differences in incidence of causes of death such as suffocation and respiratory infections, the rates and types of autopsy were analysed regarding these death causes. The number of deaths due to these causes and the development in the incidence cannot explain the variation of the incidence of SIDS, in the areas observed. For each of the three periods under consideration (1972-1975, 1976 1979, 1980-1983) the variation between institutes in SIDS-rate is relatively larger than the variation in the total rate of deaths due to these three groups of death causes. In the latest period the total rate is 1.93, 1.77 and 1.27 per 1,000 liveborn in Cophenhagen, Odense and Arhus areas, respectively. The study suggests different evaluations of the results of autopsy. A higher incidence of deaths due to congenital heart defects is seen in Arhus, where the lowest incidence of SIDS is observed. A prospective study (1987-1988) of all cases of sudden infant death in Denmark was initiated by the three forensic Institutes with the aim of evaluating possible time and regional incidence variations using identical diagnostic criteria. PMID- 2330643 TI - [Assessment of early postoperative convalescence by a simple scoring system]. AB - Fifty patients in classes 1-2 of the American Society of Anaesthesiologists (ASA) were submitted to major elective abdominal surgery. They were anaesthetised with a balanced technique and were assessed preoperatively and daily until the tenth postoperative day by a simple scoring system based on self-care. The total score fell significantly to a minimum on the first postoperative day and remained significantly decreased but with an increasing tendency until the tenth postoperative day. Patients with wound or respiratory complications had significantly lower scores than patients without complications on the sixth to ninth days. It is concluded that this simple scoring system is useful for monitoring early postoperative morbidity and it may prove of value in future investigations of surgical therapeutic regimes. PMID- 2330644 TI - [Erosion of the splenic artery in acute pancreatitis]. AB - A patient with bleeding from the eroded distal splenic artery secondary to acute pancreatitis is presented. The pancreatic tail was found to be moderately edematous without cyst, abscess or necrosis at splenectomy. The walls of the artery showed no structural changes. The postoperative course was uneventful. PMID- 2330645 TI - [Sudden infant death in Denmark in 1987 and 1988]. PMID- 2330646 TI - [Adverse effects of propofol (Diprivan)]. PMID- 2330647 TI - [Lesions of the male urethra]. AB - In cases where there is clinical suspicion of urethral lesion, blind urethral catheterization should never be performed. Establishment of a suprapubic catheter is a safe and adequate primary treatment. Retrograde urethrography may be undertaken in the subsequent diagnostic process and, in cases of simple contusions without interruption of continuity, urethral catheterization is performed. In addition, intravenous urography should be undertaken to reveal possible simultaneous lesions of the upper urinary tract. Anterior lesions rarely require further treatment whereas posterior lesions with interruption of continuity should be treated in specialized departments with special expertise in this type of lesion. Partial ruptures frequently heal without stricture formation requiring treatment. In cases of complete rupture, the best results, as regards development of late sequelae, are obtained by delayed reconstruction carried out three to four months after the trauma in the form of a two-stage operation employing a perineal skin-flap and secondary reanastomosis. In all types of urethral lesion, control miction-cystourethrography is recommended one year after the final treatment on account of the risk of stricture formation. PMID- 2330648 TI - [Extracorporeal shock wave treatment of urinary calculi. Results after treatment of the first 207 patients at the Copenhagen City Stone Center with a second generation lithotriptor]. AB - Early experience of extracorporeal shock wave lithotripsy (ESWL) using a second generation lithotriptor (Siemens Lithostar) is reported. Two hundred and seven patients underwent 272 treatments for 291 stones. There were 259 renal calculi, including three staghorn calculi and 32 ureteric calculi. Treatments were performed under local analgesia (78%) or epidural or general anaesthesia (22%) when invasive procedures had to be done in connection with the treatment. Stone fragmentation was achieved with 2,487 +/- 1,262 shocks. The first month stone clearance rate was 43%, 24% had fragments less than 6 mm and 33% had residual stones. The same figures after three and six months were 57%, 23% and 20% and 71%, 23% and 6%, respectively. Septicaemia occurred in four patients and cardiac arrhythmia in 24 patients (12%); no serious intra- or perirenal heamatomas were registered. In 7% additional procedures were required, seven patients had residual stones removed at an open operation. The Lithostar is an effective second generation lithotriptor which can be used for renal, staghorn and ureteric calculi in situ in all three segments without stone manipulation prior to ESWL. PMID- 2330649 TI - [Tuberculosis in children in Copenhagen during 1975-1985]. AB - During the years 1975-1985, 25 Danish children (less than 15 years) and 40 children of immigrants in the Municipalities of Copenhagen and Frederiksberg had tuberculosis for the first time. The children were assessed at the time of diagnosis and were retraced in 1987. The incidence of tuberculosis among foreign children was 10-40 times that among Danish children. Pronounced differences in the localizations of tuberculosis in Danes and foreigners were observed. Whereas the Danish children had exclusively pulmonary tuberculosis, 13 of the foreign children had either extrapulmonary tuberculosis or pulmonary and extrapulmonary tuberculosis simultaneously. Two of the foreign children had tuberculosis meningitis and one miliary tuberculosis. Significantly more patients with bacillary tuberculosis were present among foreigners than among Danes. No significant differences were found between the occurrence of symptoms, Mantoux positive reactions, previous Calmette vaccination or known contact with a person with tuberculosis in Danes and foreigners. Treatment was followed as prescribed and all were cured from tuberculosis. One child with tuberculosis meningitis developed slight sequelae while the remainder of the children developed somatically normally. PMID- 2330650 TI - [Bilateral paralysis of the vocal cords treated with endolaryngeal arytenoidectomy]. AB - Bilateral paralysis of the vocal cords is a serious condition in which even slight oedema of the mucosa may endanger the patient's life. Bilateral paralysis of the vocal cords is most frequently due to thyroid operations but intubation, neuritis etc are among the other causes. Tracheostomy is nearly always necessary. In an attempt to render removal of the tracheal cannula possible with retention of vocal function, the authors have performed endolaryngeal arytenoidectomy. This intervention was carried out in 28 patients. In 23 of these the cannula could be removed while various conditions prevented removal of the cannula in the remaining five patients. The authors consider that arytenoidectomy is a good form of treatment of bilateral paralysis of the vocal cords involving only a slight risk. Thereafter, there are good chances for removal of the cannula with simultaneous retention of vocal function. PMID- 2330651 TI - [Transfusion reactions after SAG-M blood]. AB - The most common type of transfusion reaction is the febrile reaction, which is often caused by microaggregates in the blood transfused. Reducing the content of microaggregates lowers the rate of transfusion reactions. SAG-M blood is depleted of microaggregates. After changing from whole blood to SAG-M blood, the frequency of transfusion reactions fell from 0,83% to 0,24%. PMID- 2330652 TI - [Peritonsillar abscess treated with puncture and aspiration]. AB - Out of 48 patients treated for peritonsillar abscess in our department in 1988, 45 were treated with needle aspiration. In 43 of these the aspiration was positive. More than one aspiration was only required in seven patients, no patient was needle aspirated more than twice. Five patients were treated with abscess tonsillectomy secondary to needle aspiration. In two cases the indication may have been failure of treatment. No complications were recorded in relation to aspiration. Followup time was seven months (median). There were two cases of recurrence of the abscess and five patients subsequently had one episode of tonsillitis after discharge. Needle aspiration is suggested as part of a selected strategy of treatment for peritonsillar abscess. PMID- 2330653 TI - [Cholinesterase in healthy adults. Significance of sex, age, weight and height for activation of P-cholinesterase]. AB - On the basis of an investigation og 193 healthy adults without occupational exposure to known cholinesterase-inhibitors, it was found that in addition to being related to the sex and ChE-fenotype, the cholinesterase activity is correlated to the weight and height of the individual concerned. Compared with the great interindividual variations, the intraindividual variations are of marginal significance for the total variation. Where dissimilar groups are concerned, comparison of the cholinesterase values corrected for variations which may be ascribed to the factors: sex, ChE-fenotype, weight and height is recommended. PMID- 2330654 TI - [Clinical-chemical testing on admission to Odense Hospital]. AB - The use of laboratory screening on admission (i.e. laboratory tests which are always requested on admission of all of the patients to the department) was investigated at Odense University Hospital. Nursing sisters were interviewed about the current practices at their departments and consultants replied to a questionnaire about their attitudes to laboratory screening on admission. Screening on admission consisted of from 0 to 24 analyses. 90% of the consultants considered that screening on admission saved time, 60% that it might reveal other diseases, 52% that it could be used as a status on control admissions and 79% that it was suitable in the preparation for operation and invasive diagnostic procedures. On the basis of a survey of the literature, it is concluded that routine use of laboratory screening on admission is not justified. PMID- 2330655 TI - [Lung cancer in Denmark 1943-1986. Cancer statistics no. 26]. PMID- 2330656 TI - Epidemiology of urolithiasis in Japan: a chronological and geographical study. AB - A nationwide survey on urolithiasis in Japan between 1965 through 1987 was carried out, succeeding the previous 1955 and 1966 studies, in an effort to evaluate chronological and geographical changes in urolithiasis among the Japanese people who are relatively racially homogenous and living with similar customs and habits, which have changed dramatically from the old Japanese to westernized modes in a very short period after the Second World War. Incidence of calcium-containing urinary stones in the upper urinary tract has been increasing in Japan since the Second World War with increasing westernization of life-style and industrialization, with the annual incidence of urolithiasis steadily increasing from 53.8/100,000 general population in 1965 to 92.5 in 1985. According to the data, 5.4% of the population may be expected to develop a urinary calculus at least once in their life time. Analysis of 69,949 stones obtained during the years from 1978 to 1987 with infrared analysis showed that 79.4% were calcium oxalate and/or calcium phosphate stones, 7.4% were struvite with or without carbonate apatite, 5.2% were uric acid or urate, and 1.0% were cystine. In the era of new treatment modalities such as the endourological surgery and the extracorporeal shock wave lithotripsy, open surgical treatments were replaced with new types of treatment in about 75% of the cases in 1985. PMID- 2330657 TI - Bilateral renal angiomyolipoma: involvement of the contralateral kidney after 25 years--an unusual case. AB - The diagnosis of renal angiomyolipoma often poses problems, both clinically and pathohistologically. With the increasing refinement of imaging techniques it is becoming potentially possible to recognize these benign neoplasms by means of ultrasound, computed tomography and magnetic resonance imaging. Electron microscopy and histochemical methods are often necessary for the correct pathological diagnosis. The problems involved are presented on the basis of the case history of a patient who suffered from renal angiomyolipoma in both kidneys with an interval of 25 years. The first tumor was diagnosed histologically as a liposarcoma 25 years ago. PMID- 2330658 TI - Two cases of anesthesia-free extracorporeal shock wave lithotripsy in stone bearing pelvic kidneys. AB - We report 2 cases of urolithiasis in pelvic kidneys and discuss the therapy of difficult stone locations with extracorporeal shock wave lithotripsy (ESWL) alone using new techniques of positioning (prone and upright sitting position) and the modified Dornier HM3 lithotriptor for anesthesia-free ESWL. PMID- 2330659 TI - Renal tissue and urinary kallikrein activity in two-kidney, one-clip hypertensive rats. AB - Renal tissue and urinary kallikrein activity were studied to assess the role of the renal kallikrein-kinin system in two-kidney, one-clip hypertensive rats. Body weight, urine volume, systolic blood pressure and urinary kallikrein activity were measured in 11 hypertensive rats and 6 normotensive rats 1, 4, 8 and 12 weeks after clipping or sham operation. The hypertensive rats used in the present study had systolic blood pressures of over 180 mm Hg 12 weeks after the operation and presented polyuria with a reduction in weight gain, which placed them in the malignant hypertension category. Urinary kallikrein activity in hypertensive rats significantly decreased from 21.7 +/- 13.3 nkat/day at 1 week to 11.6 +/- 5.5 nkat/day at 12 weeks after clipping (p less than 0.05), while urinary kallikrein activity in normotensive rats significantly increased from 23.6 +/- 8.9 nkat/day at 1 week to 43.7 +/- 16.2 nkat/day at 4 weeks after the sham operation. Significant differences were observed in urinary kallikrein activity between hypertensive rats and normotensive rats 4 and 12 weeks after the operation (p less than 0.05). Renal tissue kallikrein activity from bilaterally nephrectomized kidneys was investigated 12 weeks after the operation. No significant difference in tissue kallikrein activity was found between the two kidneys of the hypertensive rats. However, tissue kallikrein activity was significantly lower in the contralateral kidney of hypertensive rats as compared to the same kidney of normotensive rats (2.13 +/- 0.73 nkat/g in hypertensive rats vs. 3.05 +/- 0.69 nkat/g in normotensive rats, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330660 TI - Clinicopathological study on end-stage reflux nephropathy in renal-transplanted children. AB - Five children with end-stage reflux nephropathy underwent kidney transplantation at our clinic. Reflux nephropathy was studied clinically and histologically. All children had proteinuria before starting hemodialysis, and hypertension was present in 2 cases. Three children underwent antireflux operations prior to transplantation. The original kidneys exhibiting reflux were removed during renal transplantation. All original kidneys exhibited atrophy and scarring. Focal and segmental glomerulosclerosis was found in 4 cases. PAS deposition in the interstitium, suggestive of Tamm-Horsfall glycoprotein, was found in all cases. No recurrent signs of focal and segmental glomerulosclerosis have been found in the children who have been followed up from 1 to 6 years after transplantation. PMID- 2330661 TI - HLA antigens and transitional cell carcinoma of the bladder. AB - A possible association between HLA antigens and transitional cell carcinoma of the bladder was searched for in 56 patients and 200 healthy kidney donors. Statistical analysis showed that HLA antigens A23, A25, A28, BW4, BW21, BW22 and CW4 are more common in bladder tumor patients, whereas B27 and BW6 were more common in the control group. The relative risk for HLA CW4 was 2.07 (95% confidence interval 1.51-2.48). Except for CW4, these findings are inconsistent with previous reports. We believe this to be due to various misleading factors, and thus not conclusive. Even if such a statistical association exists, this appears to be clinically not relevant and, therefore, should not alter standard practice. PMID- 2330662 TI - Histological and scanning electron microscopic alterations in ileal conduit depending on the time factor. AB - Five ileal conduit biopsies, taken after 1-7 years, were examined by light microscopy and scanning electron microscopy. The total height of the lamina mucosa decreased from 700 to 275 microns. The height of the villi diminished from 550 to 50 microns; the depth of the crypts increased from 130 to 244 microns and the villus-crypt index changed from 4.2 to 0.2. Signs of chronic inflammation could be observed. Scanning electron microscopy shows that the number of microvilli per cell was markedly reduced. There was a varied picture of different stages of atrophy. After 3 years microvilli could no longer be observed. In view of the prolonged urinary contamination time, it appears to be imperative to check neobladders with regard to possible carcinoma induction. PMID- 2330663 TI - Tunica vaginalis free grafts for closure of urethrocutaneous fistulas. AB - In 32 patients a tunica vaginalis free graft was used for closure of urethrocutaneous fistulas (n = 26) or complicated hypospadias repair (n = 6). All patients had at least one operation (average 3.9) for urethral reconstruction prior to this procedure. 12 patients had recurrent fistulas (average 2.2). The technique proved to be very successful. Only 2 patients had to undergo subsequent reoperation for recurrent fistulas. The use of a free tunica vaginalis graft interposed between skin and urethra is our method of choice in the repair of recurrent or complicated urethrocutaneous fistulas. PMID- 2330664 TI - Changes in erythropoietin serum levels by extracorporeal shock wave lithotripsy. AB - Erythropoietin (EPO) serum levels were measured in 30 patients before, during and immediately after shock wave treatment by an enzyme immunoassay. Shock wave treatment was performed in the Dornier lithotripter HM3 under a constant voltage of 18 kV. In 16 out of 30 patients, an increase in the EPO serum level of over 10 U/l more than the value obtained prior to the treatment was observed. Differences ranged from 11 to 50 U/l. In 3 patients EPO serum concentration after shock wave treatment rose above the physiological limit of 54 U/l. Increased EPO serum levels have been observed after applications both under and over 1,000 shock waves. The small number of cases does not allow a statistical correlation between the number of shock waves and the elevation of the EPO serum concentration. Further investigations are necessary to define the circumstances by which an increase in EPO serum level occurs under shock wave treatment. PMID- 2330665 TI - ESWL monotherapy for large stones and staghorn calculi. AB - From December 1986 through March 1988, 52 renal units (RU) with large stone burden have been treated by ESWL monotherapy. In all patients a ureteral stent was placed prior to lithotripsy, to provide drainage of the kidney during the period of stone passage. Data of 43 RU were collected for the present report. Complications ; following treatment were infrequent (2%), whereas auxiliary measures became necessary in 32% of the patients. After a mean follow-up of 9.1 months, 54% of the patients were found stone-free. Stratification according to different stone types and compositions revealed that none of the 7 patients with complete staghorns could be completely cleared and that struvite stones had a significantly better outcome than calcium oxalate stones (75 vs. 25%). Consequently, for a large but not excessive stone burden in a normal or only slightly dilated renal collecting system, ESWL monotherapy under the protection of a ureteral stent may be a comparably safe alternative to percutaneous surgery. PMID- 2330666 TI - Childhood urolithiasis in Iran with special reference to staghorn calculi. AB - Between 1972 and 1984 148 children with urolithiasis were studied and managed at the University Clinic Children's Hospital of Teheran. In 125 children the calculi were in the upper and in 23 children in the lower urinary tract. The maximum incidence was between the ages of 5-8 and 12 years. 25 children had malformations and 16 had metabolic disorders. Cystinuria was observed in 6 and xanthinuria in 3 cases. The main constituents of calculi analyses in the upper urinary tract were calcium oxalate followed by ammonium acid urate. In the lower urinary tract ammonium acid urate and oxalate were seen with equal frequency, followed by uric acid. 16 children had staghorn calculi with an age profile of 5-13 years. Predominant symptoms were flank pain and gross hematuria. In 4 cases the calculi were bilateral. The calculi were removed successfully by pyelotomy and extensive pyelolithotomy. In 2 cases with more branched-out staghorn calculi and separate fragments, a logitudinal extensive nephrotomy was performed. In the absence of recurrent stones, renal growth and function were satisfactory postoperatively. In the majority of the cases the analyses of the staghorn calculi revealed phosphate. PMID- 2330667 TI - [Biological markers in urology]. PMID- 2330668 TI - [Continent urinary diversion in the elderly patient. Results with an ileum neobladder]. AB - From April 1986 to April 1989 an ileal neobladder was constructed in 101 male patients for complete bladder substitution following radical cystectomy. The patients were retrospectively stratified by age: 86 were over, 15 under the age of 70. No major differences were found in terms of early and late postoperative complications. However, the functional results differed markedly: whereas 89% of the younger patients achieved complete daytime and nighttime continence, only 50% of the older patients reached the same status. It is concluded that strict indications should be observed for complete continent bladder substitution in the elderly. PMID- 2330669 TI - [Early results following radical prostatectomy in patients with capsule invasion, seminal vesicle infiltration and micrometastases]. AB - One hundred thirty-three patients with prostatic carcinoma underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy between 1975 and 1988. Patients who had a localized prostatic carcinoma (less than or equal to T2b N0 M0 or less than or equal to B 2) and a small number (n = 10) with limited T3 carcinoma were considered for surgical therapy on the basis of a digital prostatic examination. Histological examination revealed locally advanced prostatic carcinoma in 89 patients with capsular infiltration or perforation and seminal vesicle involvement. Microscopic lymph node metastases were noted in 14 cases. Some patients with capsular perforation and seminal vesicle involvement received adjuvant therapy (orchiectomy or radiation). All patients with lymph node metastases were treated by orchiectomy. One local failure occurred among 24 patients with capsular infiltration within 42 months of follow-up. No failure occurred in stage pT3 disease (capsular perforation) with adjuvant therapy (n = 12) and in stage pT3 disease (seminal vesicle involvement) with (n = 9) and without (n = 12) adjuvant therapy after mean follow-up periods of 35, 42 and 52 months, respectively. Distant metastases occurred in 2 patients with stage pT3 disease (capsular perforation) without adjuvant therapy (n = 18) within a mean follow-up of 51 months, and 1 of these patients died of prostatic cancer. Distant metastases occurred in 3 patients with pT2-pT3N1 disease within a mean follow-up of 54 months: 1 of these patients died of prostatic cancer. Local failure was noted in 1 patient in this group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330670 TI - Biosynthesis of reovirus-specified polypeptides. 2-aminopurine increases the efficiency of translation of reovirus s1 mRNA but not s4 mRNA in transfected cells. AB - The effect of 2-aminopurine (2AP), an inhibitor of the RNA-dependent P1/eIF-2 protein kinase, on the expression of the reovirus serotype 1 Lang strain S1 and S4 genes in transfected simian COS cells was examined. In the absence of 2AP, the s4-encoded sigma 3 gene product was expressed about five times more efficiently than the s1-encoded sigma 1 gene product. When COS cells were treated with 2AP, the synthesis of the sigma 1 polypeptide was increased about fivefold compared to that in untreated cells even though s1 mRNA levels were not detectably altered. In contrast to the increased translational efficiency of the s1 mRNA observed in 2AP-treated cells, the translational efficiency of the s4 mRNA was not affected by 2AP treatment. However, the cytoplasmic accumulation of s4 mRNA was transiently decreased by 2AP treatment. These results demonstrate that the expression of the reovirus S1 and S4 genes in transient transfection assays is differentially affected by 2AP. Furthermore, when considered together with the prior observation that the reovirus s1 mRNA is a potent activator of the RNA dependent protein kinase relative to the s4 mRNA which is a very poor activator, the results are consistent with the suggestion that the differential translational efficiency of the reovirus s1 and s4 mRNAs in vivo may be attributed in part to their differential ability to activate the P1/eIF-2 protein kinase. PMID- 2330671 TI - Analysis of naturally occurring deletion variants of African swine fever virus: multigene family 110 is not essential for infectivity or virulence in pigs. AB - A comparison of uncloned African swine fever virus isolates with their cloned counterparts revealed the presence of genetic variants in three out of seven uncloned field virus populations tested. Five different virus clones were isolated from the uncloned KIR69 virus stock by limit dilution. Structural analysis of the variants showed that they differed by single deletions of 10-16 kilobases in the region located between 6.8 and 27 kilobases from the left DNA terminus. There was no homology between DNA sequences immediately to the left and right of the deletions indicating that the mechanism generating deletion variants was not homologous recombination. The alignment of the restriction maps of the variants with those of other virus isolates indicated that two of the variants lacked the whole multigene family 110. This was confirmed by hybridization of the viral DNA with a degenerate oligonucleotide probe. Each virus variant replicated to high titer and was virulent in domestic pigs. Therefore, the multigene family 110 was not required for viral replication or virulence in domestic pigs. The virus variants were stable upon repeated passage in swine macrophages, indicating that the generation of variants is not a frequent genetic event in vitro. PMID- 2330672 TI - Sequence characterization of the membrane protein gene of paramyxovirus simian virus 5. AB - The complete nucleotide sequence of the membrane (M) protein gene of the paramyxovirus simian virus 5 (SV5) was determined from cDNA clones of viral mRNAs. The M gene boundaries were determined by (i) primer extension sequencing on M mRNA; (ii) nuclease S1 analysis; and (iii) primer extension sequencing on viral genomic RNA. The M gene mRNA consisted of 1371 templated nucleotides. It contains a single large open reading frame that can encode a protein of 377 amino acids with a predicted Mr = 42,253. The authenticity of the predicted M protein coding sequence was confirmed by synthesis of the M protein from mRNA synthesized from cDNA. The predicted M amino acid sequence indicated it is an overall hydrophobic protein carrying a net positive charge. Alignment of the SV5 protein amino acid sequence with the M protein sequences of other paramyxoviruses indicated that these viruses fall into the following two groups: (1) SV5, mumps virus, and Newcastle disease virus; or (2) Sendai, parainfluenza virus type 3, measles virus, and canine distemper virus, with mumps virus M sequence being the most closely related to SV5. PMID- 2330673 TI - Polarity of binding of monoclonal antibodies to tobacco mosaic virus rods and stacked disks. AB - Monoclonal antibodies to tobacco mosaic virus that bind only to one end of the viral rods have been shown to recognize the surface of the protein subunit designated as the bottom, which contains the right radial and left radial alpha helices. The specificity of the antibody binding was established by immunoelectron microscopy of complexes in which the 5' end of the RNA had been exposed at the bottom of the helical virus particle. These antibodies have been shown to bind to both ends of the stacked disk aggregate of TMV protein, which is therefore bipolar. The observations on the bipolarity of this structure are inconsistent with the presumption that stacked disks are formed by aggregation of polar two-layer disks. PMID- 2330674 TI - Derivation of the nucleoproteins (NP) of influenza A viruses isolated from marine mammals. AB - The nucleoprotein (NP) genes of influenza viruses were sequenced from a variety of virus isolates derived from marine mammals: whales from the Pacific and Atlantic oceans, seal and gull from the Western Atlantic, and a tern from the Caspian Sea. In comparison to published NP sequences, we found pairs of NPs derived from avian and marine mammal isolates to be closely related, e.g., the gull-whale and mallard-seal pairs from the Atlantic Coast of the USA and the tern Pacific Ocean whale pair of the Eastern Hemisphere. Our analysis suggests that influenza viruses have been independently introduced into marine mammals from avian sources for each of our three examples. Furthermore, the closeness of the relationship in these avian-mammalian NP pairs indicates that the introductions are relatively recent. The sequences of these marine mammal NPs are avian-like and can be clearly distinguished from human NPs. Our results provide further support of interspecies transmission of influenza A viruses from the avian host reservoir directly to mammalian hosts. PMID- 2330675 TI - Analysis of retroviral packaging lines for generation of replication-competent virus. AB - Amplification of retroviral vector sequences occurs in cocultures of ecotropic and amphotropic packaging cell lines. Mixed packaging line cocultures were used to determine both the host range and time of appearance of replication-competent virus after introduction of a retroviral vector. Replication-competent virus was generated at a characteristic time for a given ecotropic and amphotropic packaging line combination. The time required to generate replication-competent virus in a packaging line varied with the number of recombination events necessary to generate replication-competent virus from the retroviral sequences present in the line. The psi 2 packaging line generated replication-competent virus within 10 days after transfection of the N2 vector into a mixture of psi 2 (ecotropic) and PA317 (amphotropic) packaging cells. Under the same conditions, it took only 3 days to develop replication-competent virus in psi 2/PA12 cocultures. The host range of replication-competent virus was used to identify the packaging line that initially generates virus. Each packaging line combination generated replication-competent virus at a characteristic time and this time period can be used as a measure of the "safety" of the packaging line and vector combination. PMID- 2330676 TI - Extracts of hamster cells abortively infected with human adenovirus type 12 are competent to support initiation of viral DNA replication. AB - Baby hamster kidney (BHK-21) cells do not allow replication of human adenovirus type 12 (Ad12) DNA during abortive infection by this virus. However, we have determined that crude extracts of BHK-21 cells abortively infected with Ad12 support in vitro the initiation reaction of Ad12 DNA replication. Synthesis of the Ad12 pTP-dCMP initiation complex by BHK extracts is two- to five-fold less than when crude infected human (KB) cell extracts are used in the reaction. Combining infected KB cytoplasmic and uninfected BHK nuclear extracts in the reaction indicates that the decreased efficiency is probably due to a lesser ability of hamster nuclear extracts to support the initiation reaction, rather than to decreased synthesis of Ad12 pTP and DNA polymerase during abortive infection, or to the presence of an inhibitor in BHK cells. PMID- 2330677 TI - Induction of tobacco chlorosis by certain cucumber mosaic virus satellite RNAs is specific to subgroup II helper strains. AB - Two satellite (sat) RNAs of cucumber mosaic virus (CMV), B2- and WL3-sat RNAs, which induce systemic chlorosis on tobacco, were inoculated onto tobacco with a number of CMV strains. Systemic chlorosis was observed only when these satellite RNAs were associated with subgroup II CMV strains. Infection of tobacco with various pseudorecombinants of subgroup I and II CMV strains, together with WL3- or B2-sat RNA, suggests that chlorosis is associated with RNA 2 of subgroup II CMV strains. Chlorosis was not induced when B2- or WL3-sat RNAs were inoculated onto tobacco with tomato aspermy virus. In contrast, the induction of chlorosis on tomato by B1-sat RNA did not show any clear dependence on the subgroup of its CMV helper strain although chlorosis did tend to be more severe in association with subgroup II CMV strains. PMID- 2330678 TI - Induction of interferon-alpha by interferon-beta, but not of interferon-beta by interferon-alpha, in the mouse. AB - The antigenicity of the interferon (IFN) produced in transgenic mice carrying an extra mouse IFN-beta gene under the control of mouse metallothionein-I enhancer promoter was examined after induction with Cd2+. Unexpectedly, IFN-alpha in addition to IFN-beta was detected in the serum. Induction of IFN-alpha was also observed when recombinant mouse IFN-beta was injected into normal mice. IFN-alpha was first detected in the circulation 6-10 hr after the administration of IFN beta, and after 12 hr, IFN-alpha became the major component of serum IFN. On the other hand, when IFN-alpha was injected, no production of IFN-beta was observed. Messenger RNAs specific for IFN-alpha and endogenous IFN-beta were detected in the spleen, though the amount of IFN-beta mRNA was much less than that of IFN alpha mRNA. These mRNAs were not detected in other organs including the liver where exogenous IFN-beta gene was markedly expressed. These observations showed that the expression of IFN-alpha is inducible by IFN-beta in the mouse, and the spleen was suggested to be the main site of production. Possible mechanisms of the induction are discussed. PMID- 2330679 TI - The U5 sequence is a cis-acting repressive element for genomic RNA expression of human T cell leukemia virus type I. AB - The long terminal repeat (LTR) of HTLV-1 consists of U3-R-U5 and contains elements which regulate the viral gene expression. In addition to these elements, we found that the U5 sequence contained a repressive element in the gene expression. Sequential deletions of the LTR substantially increased CAT expression of a LTR-CAT construct. The repressive effect was also observed at RNA level on unspliced RNA, but not on spliced RNA. These differential effects suggest that the U5 element is a cis-acting RNA element, since splicing within the R segment removed the U5 element. In the context of HTLV-1 gene expression, the U5 element would repress expression of unspliced genomic RNA of HTLV-1, but not subgenomic RNA. PMID- 2330680 TI - [Detection of "risk groups" in the early diagnosis of malignant tumors]. PMID- 2330681 TI - [ICO-10 (Thy-1) and K-20 (gp 120/200) monoclonal antibodies in immunophenotyping of solid tumors in man]. AB - ICO - 10 (Thy-1 antigen) and K 20 (gp 120/200) monoclonal antibodies proved suitable for immunophenotyping solid tumors. The following typical antigen combinations were identified with regard to reaction with those antibodies: ICO - 10+ K 20- (neuroblastoma, malignant schwannoma, neurosarcoma and soft tissue sarcomas); K 20+ ICO - 10- (cancer of the tongue and esophagus, adenoma of the adrenal cortex, adenocarcinoma of the stomach, hepatoblastoma and nephroblastoma); ICO - 10+ K 20+ (immature teratoma and cervical and esophageal leiomyoma) and ICO - 10+ K 20- (malignant fibrous histiocytoma). PMID- 2330682 TI - [Macrophage transformation of blood mononuclear cells in patients with cancer of the uterine body]. AB - Index of macrophageal transformation of blood mononuclear cells was studied in 30 cases of uterine carcinoma at various stages of the disease, and a significant decrease was observed as early as at stage I. The decrease was attributed to changes occurring in both blood serum and mononuclear cells. PMID- 2330683 TI - [Modifying effects of ascorbic acid on nitrosodimethylamine-induced carcinogenesis]. AB - In chronic experiments, albino noninbred rats were fed 20.0, 2.0 or 0.2 mg/l nitrosodimethylamine and 1000 or 100 mg/l ascorbic acid (average daily dose 100 or 10 mg/kg body weight). The study established the modifying effect of ascorbic acid on nitrosodimethylamine -- induced carcinogenesis. A decrease in tumor incidence was observed, particularly, at high level of the carcinogen. High dose ascorbic acid did not affect tumor incidence in intact animals; however, time to detection of the first tumor and mean duration of tumor development proved longer. PMID- 2330684 TI - [Clinico-morphological features of cancer of the thyroid gland associated with goiter and its surgical treatment]. AB - Concomitant pathology of the thyroid was established in 244 out of 533 (45.8%) patients with primary cancer of the organ. The latter group are main contributors to the increase in thyroid cancer incidence. Slow progression and low frequency of metastatic dissemination of cancer concomitant to other thyroid pathology suggest an inhibiting effect of benign tumors, toxic goiter and autoimmune thyroiditis on growth and dissemination of cancer which is, in turn, attributed to autosensitization to unaltered thyroid antigens. In regions nonendemic for goiter, examination and surgical treatment of nodular lesions of the thyroid should be carried out in specialized surgical clinics to prevent cancer or to assure treatment at early stages of the disease. Since solitary carcinomas are extremely likely to disseminate, surgery should be supplemented with regional lymph node biopsy involving intraoperative chromothyrolymphography. PMID- 2330685 TI - [Hysteroscopic semeiotics of cancer of the uterine body]. AB - Hysteroscopic features of preinvasive and invasive uterine cancer as well as the adjacent endometrium were studied in 103 patients. The following types of early cancer were identified with regard to pattern of growth: a single lesion, multiple lesions and diffuse involvement of the endometrium. On the basis of hysteroscopic signs, tumors were classified into polypoid, plaque-shaped, cystic mucin-producing forms and tumors with predominant atypical vasculature. Clinically apparent endometrial tumors were hysteroscopically classified as circumscribed and diffuse. The former were further subdivided into nodular, polypoid, papillary and cystic mucin-producing patterns. The credibility of hysteroscopic diagnosis was 81.8% for preinvasive and 100%--for invasive uterine carcinoma. Hysteroscopy proved instrumental in uterine cancer diagnosis, particularly, for the preinvasive form since it allows aiming sampling for histological examination to be carried out. PMID- 2330686 TI - [Use of optimizing programs of dosimetric planning in radiotherapy of gynecologic cancer]. AB - Radiation treatment of cervical and uterine cancer (intracavitary and combined irradiation using the ATAT-B, Rokus and 15M1 accelerator) is discussed to illustrate the effectiveness of mathematic procedures for choosing optimal dose regimens to suit for the anatomic peculiarities of a patient and the clinical setting. PMID- 2330687 TI - [Quality of life of cancer patients: a method for evaluating physical, social and psychological adaptation of women with cancer of the breast and uterine body]. AB - The paper describes a procedure for evaluating quality of life of patients with breast and uterine cancer and discusses the rationale for its use. The method was used in 161 cases. A correlation was established between the results provided by the procedure and those of psychologic tests. PMID- 2330689 TI - [Clinical variants in the course of chronic pancreatitis]. PMID- 2330688 TI - [Value of CEA determination in the bile of cancer patients]. PMID- 2330690 TI - [Poisoning-induced alopecia]. PMID- 2330691 TI - [Symptoms of acute inhalation lesions caused by trichloronitromethane]. AB - A study of 13 patients revealed three periods of trichlornitromethane intoxication: irritation, latent (average 2-5 hours) and development of pulmonary edema. With high concentration of trichlornitromethane vapours and long exposition the latent period was significantly shorter or was absent. The course of the first and second period was similar while the thirds proved to be different. Timely use of etiopathogenetic and symptomatic treatment was effective and result in clinical recovery. PMID- 2330692 TI - [A toxicologic hygiene evaluation of electrolytic oxygen obtained from the water in a system with a solid polymeric electrolyte]. AB - The authors evaluated the problems of hygienic aspects of oxygen obtained by the method of electrolytic decomposition of water with a different content of chemical substances in the system with a hard polymere electrolyte. On the basis of sanitary-chemical qualities and toxicological properties electrolysis gaseous oxygen may be recommended for use in creating an artificial gaseous atmosphere in hermetically sealed compartments in mixture with gaseous nitrogen (ratio 1:4). PMID- 2330693 TI - [Clinical and echoencephalographic data in assessing the outcome of meningococcal meningoencephalitis]. AB - The authors made a clinical analysis of outcomes of meningococcal meningoencephalitis in 100 patients with consciousness disturbances. It was established that the outcome of the disease depended on the time of hospitalization and degree of disturbed consciousness. The dynamics of neurological symptoms and echoencephalography of brain edema is of importance in evaluation of the prognosis of meningoencephalitis. PMID- 2330695 TI - [The use of an automated medical information system for optimizing the work of a city nephrology center]. PMID- 2330694 TI - [The diagnostic significance of lipoprotein-X]. AB - Lipoproteid-X was revealed at the onset of the disease in 59.6% of patients with acute viral hepatitis with prevalence of the cholestasis syndrome and cytolysis. Lipoproteid-X may be revealed in moderate activity of alkaline phosphatase. Lipoproteid-X was revealed in 66.7% of patients with chronic cholestatic hepatitis and biliary cirrhosis independent of the duration of the pathological process. PMID- 2330696 TI - [The clinical manifestations of chronic hepatitis]. AB - A study is presented of relations in the clinical manifestations of the disease with age using methods of multifactorial statistical analysis in 203 patients with chronic hepatitis. The diagnosis of the disease was confirmed morphologically. Results indicate that the age factor produces a modifying influence on the clinical manifestations of the disease. PMID- 2330697 TI - [The role of consultative offices on immunoprophylaxis in organizing epidemiologic surveillance of measles]. PMID- 2330699 TI - [A modification of intragastric pH measurement in patients with peptic ulcer]. AB - Intraventricular pH-metry was employed in 222 patients with pyloroduodenal localization. The advantages and value of this new technique as compared with the currently used are described and emphasized. The author discusses the perspectives of using this method of intraventricular pH-metry in mass prophylactic screenings, prophylaxis, assessment of the gastric acidity in outpatient departments, choice and control of acid-regulating treatment. PMID- 2330698 TI - [The correction of disorders of lipid-mineral composition of the bile as a method for preventing cholelithiasis]. AB - A study is presented of the lipid and mineral metabolism composition in 60 patients with diseases of the biliary tract (dyskinesias, chronic noncalculous cholecystitis, cholelithiasis) before and after treatment with a hepatoprotective agent silibor, with a dry protein mixture containing amino acids and minerals and a vitamin-mineral agent quadevit. It was established that the patients showed disorders of the mineral and lipid composition of monotypical character but of different degrees of severity in those suffering of dyskinesias, cholecystitis and cholelithiasis. Silibor treatment furthered normalization of the lipid composition of bile, while treatment with dry protein mixture--of the mineral, with quadevit--of the lipid and mineral. PMID- 2330700 TI - [Immunity in patients with peptic ulcer]. AB - Factors of unspecific defense and immunological state were evaluated in 520 patients with ulcer disease. It was established that these patients revealed disorders of excessive release into the internal medium of the body of food antigens, in particular partially split proteins. The latter induce the immune response. An increase occurs of the production of secretion of IgA in the secretions, IgG in the blood, the T-system of immunity is inhibited, the complement consumption is increased. On the basis of obtained data the author proposes a hypothesis of ulcer formations, the essence of which is that food antigens entering the body causes sensibilization of the organism with a development of an immune-complex reaction of the Arthus phenomenon type in the gastroduodenal zone. PMID- 2330701 TI - [Microwave resonance therapy in the combined treatment of gastric polyposis]. AB - A study of 70 patients with polyps and polyposis of the stomach indicates that the use of microwave electromagnetic radiation of low intensity associated with polypectomy increases significantly the treatment and improves the immediate and long-term results. Microwave resonance therapy possesses a regulating action, normalizing the bioenergy of blood cells and restoring the content of T lymphocytes. PMID- 2330702 TI - [Characteristics of the clinical course of peptic ulcer in patients with chronic alcoholism]. AB - The authors examined 112 males suffering of alcoholism and ulcer disease and revealed that the presence of ulcer diseases resulted in actualization of pathological inclination to alcohol and in case of repeat hard drinking it may result in severe recurrences of ulcer disease even in the interseasonal period, in development of complications. The results of interrelations of causes and sequels of alcoholism and ulcer disease are discussed. PMID- 2330703 TI - [Lipid metabolism in primary and combined lesions of the kidneys in pregnant women]. AB - Urinary and blood lipid metabolism was examined during pregnancy complicated by different forms of nephropathies. The pregnant with primary nephropathy and with chronic pyelonephritis showed a significant increase of lipid peroxidation products in erythrocytes while the pregnant with chronic glomerulonephritis showed high-molecular lipoproteids in the urine. A relationship was found of metabolic disorders and indices characterizing the degree of renal lesions in the pregnant. PMID- 2330704 TI - [The role of immunologic factors in the pathogenesis of urolithiasis]. AB - The role of thrombin, fibrinogen, specific and unspecific immunological reactions in the pathogenesis of urolithiasis were evaluated. It was found in the urine of patients with urolithiasis and concomitant pyelonephritis that most bacteria, leucocytes and organic substances fixed on crystalloids contained on their surfaces immunoglobulins M, G and A. The mechanisms of the possible participation of immune reactions in the pathogenesis of urolithiasis are discussed. PMID- 2330705 TI - [Diabetes insipidus in twin sisters]. PMID- 2330706 TI - [Obesity in respiratory diseases and lipid peroxidation]. AB - The authors compared body weight with indices of peroxidation of lipids in 134 patients with unspecific pulmonary diseases. Conjugated diens and dienketones rose parallelly with increase of the excessive body weight. Correlation ratios are described. Considering unfavourable effects of activation lipid peroxidation, obesity may be evaluated as endogenous metabolic risk factors for diseases of the respiratory organs. PMID- 2330707 TI - [Theopek in the treatment of patients with obstructive diseases of the respiratory organs]. AB - Data are reported on the high clinical and broncholytic efficacy of a new native preparation of theophylline of prolonged action--theopek. The drug is well tolerated by the patients, reduces the necessity in broncholytics and glucocorticosteroids and is recommended for basis therapy of patients with obstructive diseases of the respiratory organs. PMID- 2330708 TI - [Treatment via autotransfusion of UV-irradiated blood in patients with nonspecific lung diseases]. AB - An analysis of 53 patients with unspecific pulmonary diseases revealed changes of the main immunity values that were more pronounced in the older age groups. It was established that autotransfusion of UV-irradiated blood produced a normalizing effect on immunity values. The authors recommend this method in the clinical practice of unspecific pulmonary diseases, in particular, of the older age groups and intolerance of drug therapy. PMID- 2330709 TI - [The interrelation of collagen metabolism and fibrosis formation in patients with disseminated processes of the lungs]. AB - The diurnal excretion of oxiprolin with the urine and content of its fractions in the blood serum was determined in 52 patients with different disseminated processes in the lung at the active phase. An increase of the peptide-bound oxiproline and increase of its free fraction was characteristic of all patients. The protein-bound oxiprolin showed major individual changes. Its increase was often noted in patients with roentgenologically visualized fibrosis changes in the lungs, decrease--in fresh granulomatous processes. Corticosteroid therapy for 1-1.5 months produced no effect on the collagen metabolism indices. PMID- 2330710 TI - [A case of bettolepsy]. PMID- 2330711 TI - [The effect of diet therapy on the hormonal spectrum of patients with bronchial asthma]. AB - Results are reported of an investigation of the levels of cortisol, pancreatic and thyroid hormones in 38 patients with the infectious-allergic form of bronchial asthma. Unloading dietotherapy was accompanied by an improvement of the clinical course of the disease, reduction of necessity in broncholytic and hormonal agents. During the unloading dietotherapy period some variants of hormonal response to hunger were revealed. Patients with a severe course of the acidotic crisis revealed a reduction of the insulin level, changes in the cortisol dynamics, T4, a tendency to an increase of T3 in the blood. PMID- 2330712 TI - [The effect of 5-fluorouracil on lipid metabolism in patients with acute pancreatitis]. AB - The state of lipid metabolism was investigated in 72 patients with acute pancreatitis using the method of thin-layer chromatography on "Silufol" plates. It was established that the level of general phospholipids underwent a reduction in destructive pancreatitis. The level of triglycerids reduced sharply after treatment with 5-fluoruracil. The revealed changes were the basis for instituting fatty emulsions and lipid mixtures in the treatment of these patients. PMID- 2330713 TI - [The use of a sodium chloride aerosol in the combined treatment of patients with bronchial asthma and obstructive bronchitis]. AB - The authors propose a method of complex treatment of patients with bronchial asthma and chronic obstructive bronchitis using a highly disperse ionizing sodium chloride aerosol. It proved more effective in comparison with traditional methods of treatment. Availability and simplicity of this method make it possible to use it widely in out- and inpatient conditions. PMID- 2330714 TI - [Enkephalins and endorphins in unstable stenocardia]. AB - A study is presented of the blood plasma level of opioid peptides in patients with progressive stenocardia. Results indicate non-homogeneity of the patients concerning the content of neuropeptides. Two subgroups were singled out: 1. patients with progressive stenocardia of exertion in which beta-endorphin and leucin-enkephalin were above normal; 2. patients with a severe course of ischemic heart disease. Here the content of same peptides was lower than in the compared group. Similar dependence of changes of the content of methionine-enkephalin was not revealed. PMID- 2330715 TI - [The use of finoptin and alpha-tocopherol in patients with stable exertional stenocardia]. AB - A study of 59 patients of stable exertion stenocardia (functional class III) revealed an increased content of lipid hydroperoxide in lipoproteids of low and very low density that was associated with an increased level of malonic dialdehyde in of their functional activity, in particular, during physical loads. Finoptin monotherapy did not effect essentially the level of hydroperoxides in lipoproteids of low density, malonic dialdehyde in thrombocytes. Combination of finoptin and alpha-tocopherol reduced essentially the processes of lipid peroxidation, reducing, thus, the functional activity of thrombocytes at rest and loads. PMID- 2330716 TI - [The effect of anaprilin on the central and peripheral hemodynamics of patients with hypertension]. AB - A study of 38 patients with hypertensive disease revealed that anaprilin is an effective hypotensive agent. Administration of anaprilin (120-160 mg daily) produced a redistribution of the peripheral blood supply in the abdominal cavity, crus, finger and head. In regions with normal blood supply level it decreased while in regions with a reduced supply it increased. This redistribution is an important compensatory mechanism of limitation of ischemia in the regions but is worsening the blood supply in all regions in most patients. Pathogenetic treatment of patients with hypertensive disease (grade II) requires individual control of its effect on the central and peripheral hemodynamics and their early correction by adding vasodilating and diuretic agents as well as those improving blood supply of the brain. PMID- 2330717 TI - [Characteristics of the antioxidant activity of the blood plasma in patients with hypertension]. AB - A study of the peroxidation of lipids of erythrocytic membranes and blood plasma, antioxidant activity of the blood plasma in 59 patients with hypertensive disease revealed that the initial stages of the disease exacerbation increase of the antioxidant activity is caused by an intensification of peroxidation of cell membrane lipids. A less distinct increase of the antioxidant activity during remission may be due to changes of the blood plasma lipid composition. PMID- 2330718 TI - [The functional status of the heart in patients with chronic alcoholism and disorders of intraventricular conduction]. AB - An analysis of data of contrast ventriculography before and after volume load tests in 19 males suffering of chronic alcoholism with disorders of intraventricular conduction revealed signs of alcohol involvement of the heart with signs of "latent" insufficiency of the right and left ventricles manifested in an increased rate of circular shortening of myocardial fibers, terminal diastolic and terminal systolic volumes, terminal diastolic pressure. PMID- 2330719 TI - [Diagnosis and treatment of paroxysmal reciprocal atrioventricular tachycardia]. AB - The differential diagnostic criteria of paroxysmal reciprocating atrioventricular tachycardias were evaluated on the basis of a study of two clinical cases. Noninvasive (transoesophageal) electrophysiological methods were used. Evaluation of the trigger mechanism of arrhythmia, its form in comparison with data of Holter monitoring and vegetative testing allows to institute adequate antiarrhythmic therapy. PMID- 2330720 TI - [Myocardial function in patients with a history of infectious-allergic myocarditis]. AB - A echocardiographic study of the functional state of the myocardium 4-8 years after a history of infectious-allergic myocarditis in 67 patients revealed in 7.5% a moderate reduction of the contractile capacity of the myocardium and in 4.5% initial signs of left ventricle hypertrophy. The importance is stressed of early detection of this category of patients for effective prophylactic treatment aimed at prevention of myocardial insufficiency. PMID- 2330721 TI - [Morphologic changes of venous autografts before aortocoronary shunt surgery]. AB - Morphological methods helped to establish optimal conditions of storing venous autotransplants and their preparation to transplantation before the operation of aortocoronary shunting. PMID- 2330722 TI - [The attitude to disease and the work rehabilitation of patients with rheumatism and surgically treated heart defects]. PMID- 2330723 TI - [The effect of immunotherapy on the T system in lymphoma based on data from the theophylline test]. AB - An analysis is presented of the sensitivity of theophyllin test to the level of endogenous modification of E-receptors on T-cells of the peripheral blood and lymph nodes of mice with lymphoma in conditions of immunotherapy with native and Kon A or cholera neuroaminidase treated lymphoma cells. A marked inhibition of the endogenous character of theophyllin-sensitive cells in lymph nodes of mice in all methods of immunotherapy and an increase of the number of theophyllin resistant cells, more significant in mice immunized with Kon A treated cells. PMID- 2330724 TI - [Characteristics of higher nervous activity in patients after mild craniocerebral trauma]. AB - A three-four year dynamic study of 211 patients (age: 15-60 years) with a history of mild head injury revealed that the younger group of patients (from 20 to 30 years) showed within 3-4 years after the injury a more complete restoration of the higher nervous activity processes than patients of other age groups. In patients suffering of cerebrovascular diseases before mild head injury the dynamics of this restoration depended on the treatment carried out before the head injury. PMID- 2330725 TI - [Psychotherapy of patients with a history of brain concussion]. AB - The author presents data on 168 patients: 75 during the acute period of brain concussion and 93 in the remote period of brain concussion. Age of the patients from 15 to 75 years. Drug treatment in these patients was combined with psychotherapy. Data are reported on the methods of psychotherapy including patients that suffered of concomitant chronic neurological and somatic diseases. PMID- 2330726 TI - [Comment on the original contribution: Velimirovic, B.: Alternative healing methods in Austria (Wien Klin Wochenschr 101, 774-780 (1989)]. PMID- 2330727 TI - [Ergo-oxytensiometry--recommendations on methodology and evaluation]. AB - The purpose of this review is to provide recommendations for measurement and interpretation of ergooxymetry relevant to performance in out-patient departments. Ergooxymetry is the most suitable method for assessment of physical work capacity. The examination demands a distinct indication and knowledge of contraindications. On the basis of a standardized 3-step loading (VO2 = 1,050 ml/min, VO2 = 1,350 ml/min, VO2 = 1,650 ml/min; incremental loading without breaks; 6 min for each loading step) criteria for interpretation are given for PaO2, heart rate, arterial blood pressure and FEV1 respectively ROS. PMID- 2330729 TI - [A method of automated blood gas analysis]. AB - To determine the primary test parameters pH, pCO2 and pO2 one blood sample smaller than 250 microliters is necessary. In general the computer aided check of analyser's functions ensures a high quality of analytic. Nevertheless measurements can be erroneous. Therefore a control independent of the analyser's one is necessary. Blood equilibrated with defined test gases is recommended as control material for pCO2 and pO2 measurement. For control of pH measurement buffer solutions are to be used. The comparison of several analysers is an alternative method of quality control. The approximated validity of computed parameters is explained by the way of the examples oxygen saturation (O2sat) and oxygen concentration (cO2). To calculate them exactly some complemental informations (P0.5, cHb) would be needed. These informations can not be estimated by blood gas analysis. It is pointed to the different importance of the parameters pO2, O2sat and cO2 for evaluation of lung function and oxygen supply in tissue. PMID- 2330728 TI - [Bronchospasmolytic test]. AB - Bronchodilation test using metered aerosols is a simple but extraordinary reliable method of respiratory functional diagnostics. It is highly sensitive (92%) and absolutely specific (100%) for demonstration of a pathologic elevated tonus of the bronchial musculature. The importance for the choice of therapy is limited. The main advantage concerns the diagnostic classification of the obstructive bronchopulmonary diseases. PMID- 2330730 TI - [Determination of total lung capacity from the thoracic roentgen image]. AB - Formulas for calculation of total lung capacity from chest X-rays were compiled from literature. Using the total lung capacity measured by bodyplethysmography as reference, these formulas and several modifications were tested for usefulness. The product of lung area in the posterior-anterior X-rays and the largest diameter from sternum to the dorsal rib bow in the frontal X-rays was the most simple and exact roentgenological indicator of total lung capacity. 95% confidence intervals for predictive values gained by this method revealed to be of similar range as for total lung capacity estimated by the gas dilution methods in comparison to bodyplethysmography. PMID- 2330731 TI - [Comparative studies of the effectiveness of 1-day treatment and 7-day treatment with sulfamerazine/trimethoprim (Berlocombin) of patients with urinary tract infection]. AB - Insights into the pathogenesis of urinary tract infections warrant reflections on new therapeutic strategies. Of particular interest is the phenomenon of bacterial adherence to cells, as the adhesion of microorganisms to uroepithelial cells plays an important role in the development of the disease. In 21 women with an acute episode of lower urinary tract infection who were known of having chronic pyelonephritis, we studied the influence of a one-day (n = 7) and a seven-day treatment by administering the regular sulfamerazine/trimethoprime (Berlocombin) dose (2 X 2 tablets from the 2nd day, n = 7) or a reduced amount (2 X 1 tablet from the 2nd day, n = 7). All treatment regimes led to a disappearance of the clinical symptoms; however, in one case of the group receiving one-day treatment, dysuric complaints recurred as early as on day 3 after therapy. Only when employing the regular schedule of therapy, the controls of the urine cultures revealed sterility of the urine for all cases still on the 21st day after treatment. This treatment regimen most clearly influenced the ability of the microorganisms to adhere to the uroepithelial cells of the probands (in-vivo adherence). The one-day treatment was not able to reduce the rates of bacterial adherence to the cells. In all patients, the acute disease resulted in an increase in microorganisms coated with antibodies; on day 21 following therapy, however, the findings registered were as before onset of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330732 TI - [Cystic adenoma of the pancreas]. AB - Cystic neoplasms of the pancreas are rare. These tumors are differentiated into benign and potentially malignant types or in serous (microcystic), solid-cystic (papillary-cystic) and mucinouscystic neoplasms. A report is given about a 76 years old women with a serous (microcystic) cystadenoma. The cystadenoma was a chance hit of a necropsy. PMID- 2330733 TI - [Alcohol-induced hypertension]. AB - The frequency of hypertension in a group of alcoholics and the incidence of alcohol abuse in a group of patients with hypertension was compared with a collective with type-II-diabetes. There is a high relationship between alcoholics and hypertension, a lower one between alcohol abuse in the hypertension group. Chronic alcohol abuse seems to be a more important risk factor for the development of hypertension than diabetes. Genesis and therapeutic consequences of alcohol-induced hypertension are discussed. PMID- 2330734 TI - [Secondary non-Hodgkin's lymphoma of the lung--differential diagnosis of pneumonia]. AB - Two cases of intrapulmonally located non-Hodgkin lymphoma, originally subjected to stationary treatment under the suspicion of pleurapneumonia with pleurorrhea, are presented herein with the goal to show that no-Hodgkin lymphoma should be taken into account in the differential diagnosis of pleuropneumonia. About 90% of all non-Hodgkin lymphomas are accompanied by intrathoracical pathology at the time of diagnosis. The involvement of pleura as an affected organ stands at the third position in the rank order of frequencies. One fourth of all intrathoracical non-Hodgkin lymphomas are characterized by mediastinal and hilar lymph node invasion. There is no x-ray analysis of pulmonal non-Hodgkin lymphomas. Since non-Hodgkin lymphomas distribute hilifugally, investigators tend to misinterpret this syndrome as pneumonia, interstitial edema or bronchial carcinoma. PMID- 2330735 TI - [Ulcerative colitis or amebic colitis--a case report]. AB - The large intestine reacts relatively monomorphically to different stimuli. From this differential-diagnostic problems may result. The history of a patient is described which could be pursued retrospectively and prospectively over 14 years and during the course of which the correction of the diagnosis ulcerous colitis into chronic relapsing amoebic colitis was necessary. As a conclusion is emphasized that in every symptomatology of colitis primarily bacterial and parasitologic examinations of the faeces should be brought about and it must be also thought of spontaneous amoebic infections in our country. PMID- 2330736 TI - [Microangiopathic hemolytic anemia]. AB - It is reported on a more infrequent or too little regarded clinical picture within the form circle of the disseminated intravasal coagulation disturbances, the microangiopathic haemolytic anaemia (MHA). Diagnostically heuristic is the clinical triad haemolytic anaemia, thrombocytopenia and haemorrhagic diathesis. The microangiopathic haemolytic anaemia is described on the basis of a casuistics, the present knowledge about pathogenesis and therapy are discussed. PMID- 2330737 TI - [Significance of 2-dimensional echocardiography for the diagnosis of dipyridamole induced myocardial ischemia in patients with coronary heart disease]. AB - In 24 patients with coronary heart disease (group 1) and in 16 control patients (group 2) dipyridamole test was performed in combination with two-dimensional echocardiography. The studies were aimed at the comparison of sensitivity, specificity and predictive values calculated during analysis of segmental contractility of the left ventricular wall and LVEDVI, LVESVI, SVI, CI and EF in relation to ecg examination. During analysis of changes in ST segment, dipyridamole test sensitivity was 0.37, specificity--0.94, predictive confirmatory value--0.90, and predictive excluding value--0.50. During analysis of LVEDVI, SVI and CI diagnostic value of the dipyridamole test did not change (p greater than 0.05). During analysis of LVESVI and EF dipyridamole test sensitivity increased to 0.75 and 0.83, respectively (p less than 0.05). Also during analysis of segmental contractility of the left ventricular wall sensitivity of the test increased to 0.75 (p less than 0.01), while its specificity and predictive value did not change (p greater than 0.05). Two dimensional echocardiography augments diagnostic value of the dipyridamole test. PMID- 2330738 TI - [Dietary iodine deficiency in East Germany following introduction of interdisciplinary preventive use of iodine]. AB - The interdisciplinary iodine prophylaxis introduced in 1985/86 comprises the iodination of 84% of the packaged salt with 32 mg KIO3/kg salt and the use of iodized mixtures of mineral substances in animal production. At the beginning of this measure with an average renal ioduria of 19.0 +/- 1.0 micrograms J/g creatinine in the GDR there was at least still an iodine deficiency of 2nd degree. It increased from north to south: 20.3 +/- 1.0 in contrast 13.4 +/- 1.5 micrograms J/g creatinine. In the middle of 1986 a clear improvement of the supply with iodine began. The renal iodurias had more than doubled. For the GDR the mean ioduria was 43.4 +/- 0.9. The relation from north to south had, if anything, inverted: 37.3 +/- 2.1 in the north, 42-49 micrograms J/g creatinine in the centre and south of the GDR. Nearly one third of the population no more undergoes an iodine deficiency. The intrathyroidal iodine content increases. The improved supply with iodine among others is evident in: reduction of the connatal goiter below 1%, reduction of the recall rate in the TSH hypothyroidism newborn screening, normal thyroid gland mass of the newborn, reduction of the goiter frequency in children and adolescents, transient increase of the frequency of hyperthyroidism, in particular based on functional autonomies in persons older than forty years. In animal production losses of produce amounting to 181 Mic/a were eliminated. PMID- 2330739 TI - Effect of kallikrein-kinin system activation by factor XII f pretreatment on experimental hemorrhagic shock. AB - Effects of Hageman factor fragment (factor XIIf) administration on shock induction were studied in anesthetized male Wistar rats with hemorrhagic shock. Administration of factor XIIf in non-hemorrhaged rats resulted in an immediate decrease of mean arterial pressure (MAP) for 5 min and in significant increases of blood glucose, lactate and hematocrit (Hct) as well as in a strong tendency for plasma kallikreinogen (KKN) to decrease. At the beginning of bleeding (15 min after factor XIIf administration) MAP has been normalized again. During subsequent hemorrhage pretreated rats showed a sharper decrease in MAP which remained significantly lower up to 25% of estimated blood volume (EBV) and recovered more slowly to normal level after hemorrhage. Blood glucose, lactate and Hct were significantly higher in pretreated animals after hemorrhage of 30% EBV. KKN depicted significant lower values during hemorrhage and in the posthemorrhagic period. Mortality within the observation time increased from 20% (control group) to 60% (pretreated animals). The results demonstrate that prehemorrhagic kallikrein-kinin system (KKS) activation induced an increased severity of shock state with higher mortality. PMID- 2330741 TI - [Proteolytic activities of colonic mucosa]. AB - The large intestine of human and dog contains considerable activities of various aminopeptidases and genuine dipeptidases. Furthermore, a dipeptidase is described, which is independant in respect to the C-terminal configuration of the peptide. This dipeptidase is an intrinsic membrane protein. The physiological significance of these enzymes is discussed. PMID- 2330740 TI - [Enzymatic determination of glandular kallikrein in human pancreatic secretions]. AB - A method for the enzymatic determination of tissue kallikrein (EC 3.4. 21.8) in human pancreatic juice using D-Val-cyclohexyl-Ala-Arg-4-nitroaniline as substrate as well as the reaction conditions optimized for 37 degrees C are described. The reaction is characterized by the following kinetic parameters, determined according to Hanes and Eisenthal, Cornish-Bowden: KM = 2.10(-5) mol/l; Vmax = 0.800 mumol/(l.s). The coefficient of intra-assay variation (N = 10) was determined to 2.54%. The detection limit of the assay was found to be 8.63 nmol/(l.s). PMID- 2330743 TI - [The sialylation rate of apolipoprotein E in insulin-dependent (IDDM) and non insulin-dependent (NIDDM) diabetes mellitus]. AB - The degree of apo E sialylation in VLDL from serum of diabetics and controls was determined by densitometric scanning of the pherograms after isoelectric focusing of the VLDL proteins including treatment with neuraminidase. The distribution pattern of sialylation within the groups of patients and controls followed a Gaussian type. A significantly elevated level of sialylated apo E could be demonstrated in IDDM and NIDDM as compared to the controls. No correlation was found between the apo E phenotype and the diabetic state. From the correlation analysis including the parameters degree of sialylation, age, duration of diabetic state, and blood glucose pattern no significant results were obtained except a significant but only week correlation (r less than 0.3) between sialylation, age, and blood glucose in IDDM patients. Possible consequences of the elevated apo E sialylation in diabetes mellitus are discussed. PMID- 2330742 TI - [Prognosis assessment of acute myocardial infarction on the basis of temporal changes of isoenzyme activities]. AB - A new method is described for determining the prognosis of acute myocardial infarction (AMI) progress due to temporal increase in the isoenzyme, i.e. malic dehydrogenase (MDH), aspartate aminotransferase (ASAT), lactic dehydrogenase (LDH), and the increase in the creatine kinase (CK). It is shown that the time of enzymatic activity is an essential factor. If 25 hours of increase in enzymatic activity of MDH and CK are exceeded, AMI deteriorates dramatically. PMID- 2330744 TI - [Use of antibody-coated microspheres for the detection of cell surface markers]. PMID- 2330745 TI - [Historical and scientific studies in gerontology: possibilities and prospects]. AB - Basic trends of the research dealing with the historical-scientific analysis of the backgrounds, tendencies, and perspectives of gerontology are discussed. With the aim to obtain quantitative characteristics of the gerontological research area, various scientific measures have been used. A combined use of historic logical, science-metric, and expert analytical methods is necessary to improve planning and prognosis in this branch of knowledge. PMID- 2330747 TI - [Active mechanisms of dysfunction in the process of aging]. AB - Current views on the causes and mechanisms of aging are discussed. Evidence for active mechanisms which are regulatory in their origin and operate at the body and its systemic levels is presented. These mechanisms are believed to be capable of inducing changes in the organism thus bringing its functioning to the level which is characteristic of old age. Such phenomena have been observed in the immune and reproductive systems, connective tissue, skin, and liver. Examination of heterochronic parabionts revealed that these mechanisms affect the general viability of a young organism paired to an old one causing a marked reduction of the young parabiont's life-span up to the life limit of his old partner. This suggests a possible role played by aging in a species' adaptation to the environmental conditions. PMID- 2330746 TI - [Ultrastructural manifestations of blood-tissue barrier reactions to acute hypoxia in old animals]. AB - Readjustments occurring in different blood-tissue barriers (the brain, endocrine glands, heart, liver, jejunum) in response to acute hypoxia in old animals develop against the background of the preceding age-specific changes, including the adaptive ones. This results, first, in a significant narrowing of the adaptive reaction range and, second, acceleration and deepening of destructive processes in tissues and prolongation of the restoration period. PMID- 2330748 TI - [Structural-functional characteristics of chromatin fractions in the regenerating liver of adult and old rats]. AB - The transcriptional activity, nucleosomal patterns, and thermodenaturation parameters of low-active and active fractions of liver chromatin were studied in adult (6-8 mo) and old (26-28 mo) rats at 2, 4, and 6 weeks after partial hepatectomy. At 2 weeks postoperatively, there was a decrease in relative specific radioactivity (RSR) of the active chromatin fraction in adult rats, which returned to normal by the 4th week, while in the low-active fraction it was decreased throughout all the studied regeneration periods. The decrease of the low-active fraction RSR was attended with changes in the nucleosomal organization and DNA-protein interactions revealed by electrophoresis and thermodenaturation. Old rats were found to have the active fraction RSR unchanged throughout all the studied regeneration periods. The low-active fraction RSR increased at 2 and 4 postoperative weeks and decreased to the level of intact liver at 6 weeks. Electrophoretic analysis and parameters of thermodenaturation of the low-active fraction reflect changes in the chromatin conformation associated with transcription activation and, at the same time, reveal its higher compactness in nucleosomal structures. Age differences in the time-course of structural rearrangements and transcriptional activity of liver chromatin during regeneration may be responsible for different rates of postoperative liver restoration in adult and old rats. PMID- 2330749 TI - [Gerontology in the USSR: yesterday, today and tomorrow]. AB - Main stages of the development of gerontological studies in this country are specified. The genetic mechanisms of aging, intra- and supracellular regulation, age-specific immunological shifts, and functional systems of the organism are defined as priority targets of research. More attention is to be focussed on the development of the biological age criteria, studies of interrelationships between aging and age-specific pathology, analysis of age factors underlying main diseases of the old, on the development and trial of new geriatric drugs, and the search for effective life-prolonging agents. In the field of social gerontology, special attention is to be paid to the research into the causes of relatively low life expectation in this country, the lifestyle rationale, and to the improvement of medico-social services for the elderly population. PMID- 2330750 TI - [Hereditary effects on the rate of aging in humans]. AB - Twin samples of various ages (154 pairs) were studied in transverse section and under longitudinal observation to assess the quantitative correlation of genetic and environmental influences on the age changes of 320 characters specifying different functional systems of the human organism: nervous, cardiovascular, respiratory, immune, endocrine, locomotor, metabolic, somatic, and mental. An evidence was obtained for a decrease in relative role of inheritance and increase in environmental (both systemic and scholastic) influences on the age-related changes in various organs and body systems of humans in aging. Therefore, the rates of aging and health status in humans may be controlled to some extent by exerting selective influences on the corresponding environmental factors. PMID- 2330751 TI - [Ultrastructural features of hydroxyapatite crystals of thoracic vertebrae in the middle-aged and aged persons]. AB - Bone tissue samples of thoracic vertebrae taken from 32 cadavers of males and females who had suddenly died at ages were examined ranging from 20 to 45 and from 70 to 89 years. The samples were studied by means of quantitative phase X ray analysis which showed the mineral component of the crystalline phase to be 55.8 +/- 2.1 and 56.6 +/- 2.2 per cent in the young men and women, and that of the older-age group to be 63.9 +/- 1.9 and 66.1 +/- 2.6 per cent, respectively. The hydroxyapatite crystals had the shape of a hexagonal prism with 23.8-27.3 nm allongated along the C axis. The crystal dimensions along the a axis in the young males were 7.0 +/- 0.15 nm, that of females were 6.8 +/- 0.2 nm; in the old-age group, the dimensions were 7.7 +/- 0.2 and 7.4 +/- 0.14 nm, respectively. The volume of the crystallized particles in the young was 1387 +/- 66 nm3 and increased with age to 1748 +/- 117 nm3. The findings on the ultrastructure of the mineral component and its age-related changes may be used to study the physicochemical properties of the bone and to reveal the essence of aging of the locomotor apparatus and of the organism as a whole. PMID- 2330752 TI - [Current view on the pathogenetic factors of hypoxia in middle-aged and aged persons]. AB - Pulmonary ventilation, gas exchange, respiration biomechanics, respiratory function of the blood, and the tissue level of PO2 in functional tests have been studied in a group of healthy individuals aged 20-106 years. Aging has been found to be associated with oxygen deficiency including the circulatory and tissue hypoxia elements. The relationship between hypoxia and aging has been confirmed, and the mechanisms by which specific oxygen-deficiency components develop have been outlined. The adaptive hypoxia-related changes in elderly and senile ages have been specified. Based on the current concepts of the pathogenic factors underlying hypoxia in aging, the methodologies are proposed to reverse the hypoxia-related changes in these age groups. PMID- 2330753 TI - [Age-related features of the functional state of the brain in patients with circulatory encephalopathy]. AB - Complex clinico-physiological examinations was performed in 300 patients of middle and old ages with early and pronounced dyscirculatory encephalopathy of atherosclerotic and, in most cases, hypertensive etiologies. The cerebral hemodynamics was found to be relatively independent of the central one in patients with early atherosclerotic encephalopathy; the level of the systemic circulation and that of the median regional cerebral flow were found to correlate in early and advanced hypertensive encephalopathy cases. The cerebral function was shown to be more associated with the cerebral flow in the early encephalopathy in elderly patients than in middle-aged ones. The individual and personal traits of the patients were largely related to the disease stage rather than to the predominant etiological factor. PMID- 2330754 TI - [Use of retrospective (anamnestic) method in cross-sectional and longitudinal studies in social gerontology]. AB - The efficacy of using the retrospective method to obtain additional information for both cross-sectional and prospective studies is demonstrated. The life pattern, time course of individual or familial health-status changes in the periods preceding the prospective study enhance the informative value of study findings, provide monitoring the stability of the influence of the studied health factors, and make them epidemiological. PMID- 2330755 TI - [Physiological rehabilitation of the middle-aged in the industry (formulation of current problems)]. PMID- 2330756 TI - [Geriatrics--an important field of clinical medicine]. AB - The topical aspects of geriatrics, which is believed to be an important part of clinical medicine, are overviewed. The age-specific features of therapeutic actions in elderly and senile patients are delineated. A special emphasis is given to the rehabilitation measures which are to be taken on a person's retirement, as well as to the significance of the motor activity and rational nutrition in the prevention of early aging. PMID- 2330757 TI - Reference-material-based collaborative test of flame atomic absorption spectroscopic determination of calcium and magnesium in foods and biological materials. AB - A flame atomic absorption spectroscopic (FAAS) method is described for the determination of calcium and magnesium in a wide variety of foods and biological substrates. Results for reference materials (n = 9) are presented that demonstrate the validity of the procedure. Samples are digested with nitric acid at 150 degrees C in a pressure decomposition vessel, diluted and adjusted to pH 2 with ammonia. Lanthanum chloride solution is added to suppress phosphate interferences and the ionization of calcium and magnesium in the AAS flame. Additional dilutions are made as appropriate, whereupon the atomic absorption of calcium and magnesium is measured in an oxidizing air-acetylene flame. The wavelength settings for calcium is 422.7 nm and for magnesium 285.2 nm. The method was tested in a collaborative trial involving a milk powder practice sample and four test samples, all of which were reference materials. Participants were requested to carry out duplicate determinations exclusively. Results were obtained from 12 laboratories. However, the results of 3 laboratories had to be rejected for various reasons. The remaining set of data was statistically evaluated according to ISO 5725; the method of analysis proved to be precise and accurate. Coefficients of variation values for calcium ranged from 1.19% to 4.44% within laboratories (CVr) and from 5.30% to 15.9% between laboratories (CVR). For magnesium, the corresponding values were CVr, 1.07% to 3.52% and CVR, 3.07% to 5.99%. The method is recommended for the determination of calcium and magnesium at the levels considered in foods and biological substrates. PMID- 2330759 TI - Formation of acids, lactones and esters through the Maillard reaction. AB - From a glucose/glycine reaction mixture acids, esters and lactones were isolated and identified. Sugar degradation products could also be determined as benzimidazole derivatives after reaction with o-phenylenediamine. Results derived from model systems suggested possible reaction pathways leading to some of the isolated substances. A lactic acid ester is formed as a product of an unstable beta-pyranone intermediate. A 3-deoxyhexosone serves as a precursor of two furanolactones. PMID- 2330758 TI - [Ion chromatographic analysis of cations and anions in mineral water]. AB - For the simultaneous analysis of the cations Li, Na, K, Ca, and Mg as well as Mn and the anions hydrogen carbonate, chloride, sulfate and nitrate, silica gel- and polymer-based ion exchange materials with conductivity and spectrophotometric detection combined with a post-column derivatization system (PAR-Zn-EDTA for Ca, Mg, Mn) and also an ion-pair system with RP-18 phase were compared with a view to their application to mineral water samples. It is possible to determine Li, Na, and K in such samples with or without the suppressor technique using polymer columns. A polybutadiene maleic acid silica gel cation exchanger material makes feasible simultaneous analysis of alkaline and earth alkaline metals. Ca, Mg, and hydrogen carbonate, chloride, sulfate and nitrate are analyzed in less than 16 min using a silica gel anion exchanger with EDTA as the eluent. To stay within the linear range of the calibration function it is necessary to perform two injections in different dilutions (between 1:4 and 1:500) due to the different concentration ratios. For the analysis of manganese above 100 micrograms/L a system with the cation exchanger Partisil SCX and the eluent ethylenediamine/oxalate with post-column derivatization is used. The sample pretreatment is done by reduction with thiosulfate. A total of 15 different mineral waters were analyzed with all the systems and the results were compared with those of reference methods (AAS, potentiometry), showing good conformity. PMID- 2330760 TI - [Extending the survival time of allogenic rat kidney transplants by PUVA treatment of the recipient]. AB - After temporary postoperative PUVA treatment of the graft recipient the survival time of rat renal allotransplants is significantly prolonged. In the semiallogeneic F1 model all animals survived without rejection signs. The mechanism of action should be cleared and as adjunctive method introduced into clinical organ transplantation. PMID- 2330762 TI - [Effect of kidney occlusion on survival in renal cell carcinoma: a 10-year retrospective study]. AB - 84 out of 116 patients suffering from renal cancer with comparable tumor stages were nephrectomized. 39 out of these 84 patients have had an additional embolization preoperatively. The survival rate and the development of metastases did not show any significant difference between only nephrectomized and occluded plus nephrectomized patients. PMID- 2330761 TI - [Follow-up of the transplantation of contaminated kidneys]. AB - 102 kidney transplantation were performed in 1987 in the Kidney Transplant Center at Berlin. The course of 22 contaminated grafts (22%) was analyzed. The main bacteria were staphylococcus aureus and pseudomonas aeruginosa. In 6 out of 22 contaminated transplants (27%) a delayed wound healing did occur. In 2 cases the infection was the cause of graft removal and 2 patients died due to septical complications of the contaminated graft. Therefore, the contaminated kidney is a potential risk for graft and patient survival and strong asepsis and effective perioperative antibiotic prophylaxis is necessary. PMID- 2330763 TI - [Splenogonadal fusion]. AB - The splenogonadal fusion is a rare but benign anomaly. The diagnosis is usually given at operation or histologically after operation. In about 50% of the patients who undergo surgery for scrotal tumor, an unnecessary orchidectomy is performed due to clinical unawareness of this rare condition. A case of splenogonadal fusion belonging to the continuous type is presented to illustrate problems of this anomaly and point out the importance of intraoperative microscopic sections. PMID- 2330764 TI - [Experiences with plasmapheresis in the treatment of vascular rejection following kidney transplantation]. AB - In the first 6 weeks after kidney transplantation 15 patients suffering from vascular rejection were treated by 46 plasmapheres. In transplants with additional interstitial rejection the plasmapheresis was introduced after failure of ATG therapy. In 1 patient no histological confirmation was done. In 4 patients the plasmapheresis was successful and in 6 patients suffering from combined vascular and interstitial rejection the ATG therapy was successful only after initial plasmapheresis. In 4 cases the therapy failed to reverse rejection. The early use of plasmapheresis is recommended to obtain the best results. PMID- 2330765 TI - The yeast genus Trichosporon spec. LS3;molecular characterization of genomic complexity. AB - The genomic structure of an industrial yeast strain Trichosporon spec. LS3 was compared with Trichosporon adeninovorans type strain CBS 8244. The cot values, the portion of single copy sequences (CBS 8244: 10.9 x 10(9) D, LS3: 10.6 x 10(9) D) as well as of repetitive sequences (CBS 8244: 6.0 x 10(9) D, LS3: 5.5 x 10(9) D) per haploid genome and genome complexity of these strains (CBS 2844: 16.9 x 10(9) D, LS3: 16.1 x 10(9) D) have been analysed. Both strains show a high genome complexity. The mitochondrial DNA content was measured and compared. No plasmidal DNA was identified for both strains. A survey of the data of genomic DNA made it possible to postulate for each of both strains a haploid set of chromosomes. The intraspecific reassoziation values of the nuclear DNA from the strain LS3 and CBS 8244 are interpreted to confirm classification of these strains based on physiological and genetical properties into one species Trichosporon adeninovorans. PMID- 2330766 TI - Fungi of the house dust in Riyadh, Saudi Arabia. AB - 30 species belonging to 18 genera were isolated from floor dust of 30 homes in Riyadh. Out of them 16 species and 10 genera were isolated from dust of air conditioners of the same homes. The most common genera in floor dust were Aspergillus, Penicillium and Cladosporium. Aspergillus repens, A. amstelodami, A. versicolor, A. fumigatus, Penicillium purpurogenum, P. crustosum, Cladosporium cladosporoides and C. herbarum were frequently isolated. The most abundant genera in air conditioner dust were Aspergillus and Penicillium. Aspergillus fumigatus, A. ochraceus, A. terreus, Penicillium oxalicium and P. crustosum were most frequent species. PMID- 2330767 TI - [Duodenal atresia. Experiences with 145 patients]. AB - 145 children with duodenal atresia were operated on between 1971 and 1988. 57 were premature, 48 newborn, 11 toddlers and 5 older children. Once the immediate perioperative phase is overcome, the postoperative prognosis is determined only by the severity of associated anomalies. Most atresias were found to be located prepapillary. Trisomy 21, malrotations and vitium cordis were the most frequent associated anomalies. Relaparotomies were required in 21%, mostly because of adhesions. PMID- 2330769 TI - [Blunt kidney injuries in children]. AB - Trauma, primarily due to traffic accidents, is the most common cause of death in childhood. In the context of abdominal trauma, the probability of injuries to urinary organs in children is higher than in adults. Peritoneal lavage and use of the CRAMS scale have proved to be reliable methods for assessment and planning of therapy for traumatised children. When it comes to treatment for splenic rupture, efforts should be made to preserve the greatest possible amount of splenic tissue to prevent post-splenectomy sepsis. PMID- 2330768 TI - [Stomach perforation in the neonatal period and in children]. AB - Among the upper gastrointestinal tract perforations in infants and children, the gastric perforations were predominating. With exception of peptic ulcers, localization was found mainly in the upper parts of the stomach regarding to mechanical originating factors. Mortality depends on prematurity and additional injuries as well as the basic disorders. PMID- 2330770 TI - [Late results of corrective surgery of protruding external ears]. AB - In the period 1974-1984 corrections of the external ear were carried out on 343 patients using the Haecker/Joseph method for flattening and the Converse method for anthelixplasty. Check-ups on 147 patients revealed late results to be "improved to very good" in 92.5% of cases on the basis of metrical data and aesthetic appraisal of the corrected external ear. Provided that there is a firm indication and exact pre-operative diagnosis combined with good surgical technique and post-operative care, these two methods represent well-tried procedures with a high success rate. PMID- 2330771 TI - [High ileus in a newborn infant with total intestinal aganglionosis]. PMID- 2330772 TI - [Respiratory insufficiency in the infant--foreign body aspiration!]. PMID- 2330773 TI - [Infarction of Meckel's diverticulum in infants]. PMID- 2330776 TI - [An evaluation of the sensitivity to antiseptic preparations of clinical strains of microorganisms in the family Enterobacteriaceae]. AB - Classical enterobacterial strains are sensitive to the working concentrations of pervomur, dioxydine, resorcinol, sodium sulfacyl, iodopyrone, chlorhexidine and boric acid, resistant to the action of cetyplyridinium chloride, rivanol, roccal and ethonium. In enterobacterial populations strains with acquired resistance to chloramine B, iodopyrone, chlorhexidine and resorcinol are present. Hospital strains of enterobacteria are characterized by higher, in comparison with extrahospital strains, resistance to ethonium, sodium sulfacyl, lodopyrone, chloramine B and resorcinol. PMID- 2330775 TI - [The use of a molecular DNA probe based on the cloned cytolysin gene for the identification of Legionella]. AB - A molecular DNA probe has been obtained on the basis of recombinant plasmid pNIG carrying the Legionella cytolysin gene. The use of this probe for the identification of different Legionella species and other microorganisms has shown that it may serve as the species-specific marker of L. pneumophila. The probe has been used for the identification of new Legionella-like strains isolated from the environment. PMID- 2330774 TI - [The life strategy and self-regulation mechanisms of populations of the causative agents of sapronoses (exemplified by Pseudomonas pseudomallei)]. AB - The strategy of the selection (life) of P. pseudomallei has been defined as C competitiveness, combining the advantages of the limited (r and K) types of the ecological strategies of microorganisms and ensuring their good capacity of survival in soil biota. The self-regulation mechanisms of P. pseudomallei populations in the environment are determined by the type of their strategy of selection, which also determines the place of this species among other organisms inhabiting the soil. C-competitiveness of P. pseudomallei permits the realization of the self-support of its populations under changing conditions of their habitat, in particular in vivo. PMID- 2330777 TI - [The situation regarding parasitic diseases in the USSR]. PMID- 2330778 TI - [The characteristics of suppurative meningitis morbidity caused by Streptococcus pneumoniae and Haemophilus influenza type B]. AB - Of the 1,018 patients with purulent bacterial meningitis, hospitalized at the 2nd Clinical Infectious Hospital in Moscow during the period of 1980-1987, the diagnosis was confirmed in 54.7%; of these, meningitis of pneumococcal etiology was established in 44.8% and meningitis caused by H. influenzae, type b, in 23.8% of the patients. In meningitis of pneumococcal etiology high risk groups included mainly adults, especially those over 50 years, and children under 3 years of age. In meningitis of H. influenzae etiology high risk groups included mainly young children under 2 years of age. Meningitis of pneumococcal etiology was characterized by considerable death rate (on the average, 20%), while in meningitis of H. influenzae etiology death rate was 3 times lower. Pneumococci of serotypes 1, 3, 6, and 19 were found to be of the highest etiological importance for adults and pneumococci of serotypes 19, 6, 12, and 1, for children. In recent years greater etiological role of serotype 42 in adults was noted. The study of the spread of meningitides of different etiology is a high-priority task for this country. PMID- 2330779 TI - [The antigenic characteristics of field strains of the rabies virus from different districts of the USSR studied using antinucleocapsid monoclonal antibodies]. AB - 98 rabies virus strains isolated from different species of wild and domestic animals have been studied by means of 36 monoclonal antibodies obtained from the Wistar Institute (USA) and 3--of the Federal Research Center on Viral Diseases of Animals (FRG). The antigenic variants determined in this study have been analyzed in comparison with the data obtained in other regions of the world, thus establishing the spread of these variants and their relationship with different species of animals. PMID- 2330781 TI - [The effect of bacterial and synthetic peptidoglycans on the toxicity of a cell free pertussis preparation]. AB - The influence of bacterial and synthetic peptidoglycans on the toxicity of acellular pertussis preparations (APP) has been studied in the mouse weight gain test and in the endotoxic shock development test on mice treated with Actinomycin D. The data obtained in these tests indicate that the immunomodulators (IM) under study are capable of changing (increasing or decreasing, depending on the dose) the toxic properties of APP. The antitoxic action of IM, established in this study, depends on the combination of the doses of IM and APP and the time elapsed from the time of immunization. The possibility of using these IM in a dose of 0.0001 microgram for reducing the LD50 of APP has been established. The use of IM belonging to the group of bacterial synthetic peptidoglycans for the development of acellular pertussis vaccines with reduced reactogenicity has been shown to hold much promise. PMID- 2330783 TI - [The immunocorrective effect of laser reflexotherapy in experimental influenza infection]. AB - The influence of two schemes of laser acupuncture on some cell-mediated and humoral immunity characteristics of mice, as well as on their nonspecific antiviral resistance, in acute experimental influenza infection has been studied. The use of both schemes has been found to considerably decrease the severity of infection, enhancing the activity of lymphocytes of infected mice in the graft versus host reaction, the O2-producing activity of alveolar macrophages and modulating the ratio of antihemagglutinins and nonspecific antiviral inhibitors in the blood serum. PMID- 2330782 TI - [The role of T-lymphocytes in the development of a humoral immune response to the corpuscular antigen of Staphylococcus aureus]. AB - The dependence of humoral immune response and the formation of immunological memory to corpuscular staphylococcal antigen (CSA) on the T-system of immunity was studied in experiments on B-mice and on mice with the congenital absence of the thymus (nude). Primary and secondary immune response to CSA in athymic mice was found to be considerably less than in normal animals. After the repeated immunization of genetically athymic mice the pronounced secondary reaction of the formation of antibodies to CSA was observed. As shown in this investigation carried out with the use of adoptive transfer techniques, the induction of memory B-cells to CSA may occur in animals with congenital or experimentally induced T immunodeficiency. The conclusion was made on the T-dependence of humoral immune response to CSA, the formation of immunological memory to this antigen being relatively T-independent. PMID- 2330780 TI - [The immunological diagnosis of peptostreptococcal infection]. AB - The work deals with different methods for the diagnosis of anaerobic streptococcal infection, experimentally tested and clinically approved in the examination of children with acute pneumonia. The passive hemagglutination test, the immune rosette formation test and the specific lymphocyte blastogenesis test were used for diagnosis. As sensitin and antigen, the preparation of the peptostreptococcal bacterial mass was used. The diagnostic titer of antibodies to anaerobic streptococci was 1:160. A twofold and greater increase in the number of antigen-dependent rosette-forming lymphocytes and in specific blast transformation in the presence of the diagnostic antibody titer confirms the etiological role of anaerobic peptostreptococci in the development of pneumonia in children. PMID- 2330784 TI - [The toxin-producing capacity of populations of Vibrio cholerae of different origins]. AB - As the result of the study of toxin formation in 165 V. eltor strains having different virulence, most of the virulent cultures have shown stable toxin production, though 5-10% of their colonies have proved to be nontoxigenic. In faintly virulent strains toxin production was found to be unstable, which is indicative of the heterogeneity of their population composition as regards their capacity for toxin formation. The population of avirulent strains consists mainly of nontoxigenic clones (95.7%). PMID- 2330785 TI - Fine structural characteristics and synaptic connections of trigeminocerebellar projection neurons in rat trigeminal nucleus oralis. AB - In order to classify the presynaptic terminals contacting trigeminocerebellar projection neurons (TCPNs) in rat trigeminal nucleus oralis (Vo), electron microscopic examination of sequential thin sections made from TCPNs located in the border zone (BZ) of Vo, labeled by the retrograde transport of horseradish peroxidase, was undertaken. The use of BZ TCPNs, labeled in Golgi-like fashion so that many of their dendrites and axons were visible, allowed for the determination of the distribution of each bouton type along the soma and dendrites, as well as for the characterization of the morphology and synaptic relations of the labeled axon and its terminals. Three types of axon terminals contacting labeled BZ TCPNs have been recognized, depending upon whether they contain primarily spherical-shaped, agranular synaptic vesicles (S endings); predominantly flattened, agranular synaptic vesicles (F endings); or a population of pleomorphic-shaped, agranular synaptic vesicles (P endings). The S endings represent the majority of axon terminals contacting labeled BZ TCPNs and establish asymmetrical axosomatic and axodendritic synaptic contacts. Many S endings are situated in one of two types of synaptic glomeruli. One type of glomerulus has a large S ending at its core, whereas the other contains a small S ending. Large-S-ending glomeruli include only labeled distal dendrites of BZ TCPNs; small-S-ending glomeruli contain either a labeled soma, proximal dendrite, or distal dendritic shaft. The remaining S endings are extraglomerular, synapsing on distal dendrites. P endings are less frequently encountered and establish intermediate axosomatic and axodendritic synapses. These endings exhibit a generalized distribution along the entire somatodendritic tree. F endings make symmetrical axodendritic synapses with distal dendrites, are only found in glomeruli containing small S endings, and are the least frequently observed ending contacting labeled BZ TCPNs. The majority of axonal endings synapsing on labeled BZ TCPNs are located along distal dendrites, with only a relatively few synapsing terminals situated on proximal dendrites and somata. The axons of labeled BZ TCPNs arise from the cell body and generally give rise to a single short collateral near their points of origin. This collateral remains unbranched and generates several boutons within BZ, while the parent axon acquires a myelin sheath and, without branching further, travels dorsolaterally toward the inferior cerebellar peduncle. The collateral boutons resemble extraglomerular S endings. They contain agranular, spherical-shaped synaptic vesicles and make asymmetrical axodendritic synapses with small-diameter unlabeled dendritic shafts in the BZ neuropil. PMID- 2330786 TI - Random-sequence stimulation of the G1 hair afferent unit. AB - Impulse trains were recorded from the parent axon of the cat G1 hair afferent unit. Separate random (Poisson-like) trains of mechanical stimuli were applied to two coinnervated receptive field hairs individually or concurrently. The objective was to determine whether the parent axonal impulse train elicited by dual-hair stimulation was due to a temporal combining ("mixing"; Fukami, 1980) of the impulse trains elicited in the parent axons by the same stimulation to each hair alone. Both impulse rates and patterns were assessed. During single-hair random stimulation, impulse trains differed from stimulus trains, having lower mean rates and short-interval doublets. During dual-hair random stimulation, mean impulse frequencies were on average 36% less than those predicted for mixing. There were no correlations between stimulus amplitude and departures from mixing. As a further test of the mixing hypothesis, the two single-hair-elicited impulse trains were temporally merged (i.e., superimposed to form one impulse train). Such merged impulse trains were compared with the corresponding dual-hair elicited impulse train. Dual-hair-elicited frequencies were typically less than those of the merged trains, despite the use of an absolute-refractory-period criterion during merging. The impulse patterns elicited by dual-hair stimulation usually differed from the merged-train patterns. Temporal coupling between stimuli and impulses was either variable or absent during single-hair random stimulation; such coupling was altered during dual-hair random stimulation. In summary, this work showed that the dual-hair responses could not be predicted from the single-hair responses. Limitations of the mixing hypothesis and possible biophysical mechanisms in the axonal arborization are discussed. The results are consistent with a general hypothesis of analog processing within the arborization of the parent axon. PMID- 2330788 TI - Topographic organization of the peripheral projections of the trigeminal ganglion in the fetal rat. AB - Retrograde tracing with true blue (TB) and diamidino yellow (DY) was used to determine the topography of the peripheral projections of the trigeminal (V) ganglion in rats on embryonic day 16 (E-16; E-0 was the day of conception). On E 16, the earliest age at which we were able to accomplish retrograde tracing successfully, the topographic organization of the V ganglionic projection to the periphery was quite adult-like. Cells projecting to the vibrissa pad were restricted to the ophthalmic-maxillary portion of the ganglion, with those innervating dorsal row follicles located medially and those supplying ventral row follicles located laterally. Injections of tracer into ophthalmic skin and/or the cornea labeled cells that were tightly clustered in the most dorsal and anteromedial portion of the ophthalmic-maxillary region. Injections of tracer into the lower jaw or the skin just rostral to the ear labeled cells that were restricted to the lateral, mandibular part of the ganglion. None of the combinations of injections we carried out resulted in large numbers of double labeled V ganglion cells. Injection of TB into the vibrissa pad and DY into the upper lip produced a small number of double-labeled ganglion cells. This was also the case for paired injections of TB and DY into the lower jaw and lip, respectively. No more than 15 such cells were observed in a ganglion. These findings suggest that the substantial cell death that has been reported to occur in prenatal V ganglion development (Davies and Lumsden, 1984) is probably not involved in the correction of major peripheral targeting errors by the axons of V ganglion cells. PMID- 2330789 TI - Extensive dual innervation and mutual inhibition by forelimb and hindlimb inputs to ventroposterolateral nucleus projection neurons in the rat. AB - The stimulation of brachial plexus and sciatic nerve resulted in a precisely timed, synchronous volley of inputs to ventroposterolateral (VPL) neurons from either forelimb or hindlimb. Such stimulation activated sensory fibers of all modalities and was therefore modality-nonspecific. Extracellular recordings of modality-nonspecific single-unit evoked responses from VPL showed that 13% of VPL projection neurons responded to both forelimb and hindlimb inputs. We also demonstrated mutually inhibitory interactions between inputs from forelimb and hindlimb in 45% of VPL units. Unlike the somatotopic map produced by others using modality-specific inputs, the modality-nonspecific evoked response map of VPL had a broadly overlapping distribution of evoked responses. This was especially true for the more caudal aspects of VPL. When the delivery of stimuli was appropriately timed, forelimb inputs caused the inhibition of responses to forelimb stimulation; similarly, hindlimb inputs inhibited responses to forelimb stimulation. The inhibition had a variable duration that may reflect a combination of processes, including recurrent inhibitory collateral input from the thalamic reticular nucleus (TRN) or an intrinsic hyperpolarizing inhibitory afterpotential of the VPL neuron. The presence of an extensive converging input on VPL neurons and an inhibitory correlate to this overlapping of inputs may explain the shifting of VPL maps following lesions of peripheral nerve, spinal cord, or dorsal column nuclei (DCN). PMID- 2330787 TI - Responses of rat trigeminal ganglion neurons to movements of vibrissae in different directions. AB - The response properties of 123 trigeminal ganglion neurons were studied, using controlled whisker deflections in different directions. When the distal end of the whisker was initially displaced 5.7 degrees (1 mm) from its neutral position, 81% of the cells responded with statistically more spikes/stimulus to movements in one to three of eight cardinal (45 degrees increment) directions than to the others. The more directionally selective the cell, the more vigorous was its response. On the basis of statistical criteria, 75% of the cells were classified as slowly adapting, 25% as rapidly adapting. A number of quantitative analyses indicated that slowly adapting units respond more selectively than rapidly adapting cells to the direction of whisker movement. Differences in directional sensitivities of rapidly and slowly adapting cells appear to parallel differences between their putative mechanoreceptive endings and the relationships between those endings and the vibrissa follicle's structure. Comparisons between the response properties of peripheral and central neurons in the vibrissa-lemniscal system indicate that the afferent neural signal is progressively and substantially transformed by mechanisms that function to integrate information from different peripheral receptors and from different, individual vibrissae. PMID- 2330790 TI - Intraoperative collection of shed blood with citrated compresses for autotransfusion. An experimental study in pigs. AB - Six pigs were used to study whether the collection of shed blood by means of surgical compresses instead of suction traumatizes such blood. In an in vivo part of the study, the whole blood volume of the pigs was retransfused after treatment with citrated compresses, and in an in vitro part the blood was treated extensively with compresses and analyzed. All animals survived, with a minor fall in hemoglobin after 48 hours and a rise in serum citrate concentration at the end of the experiment. A study of the coagulation system revealed no important change after retransfusion of compress-treated blood. In the in vitro part of the study, repeatedly squeezing blood from the compresses increased the concentration of free hemoglobin to a maximum of 5 g/l after ten squeezes, whereas platelets were numerically unchanged. The study indicates that collecting shed blood by means of surgical compresses may be a safe and efficient method. PMID- 2330791 TI - The reliability of frozen section diagnosis. AB - We undertook a retrospective study of 594 consecutive diagnosis by frozen section. Clinically important discrepancies were found between the frozen section and final diagnoses in 18 (3%), and unimportant discrepancies in 35 (6%). The reasons for the discrepancies were misinterpretation in 22 (41%), the presence of focal lesions in 29 (55%), and technical errors in 2 (4%). There were 4 false positive and 18 false negative diagnoses, giving a sensitivity of 93% and a specificity of 99%. Diagnoses from frozen sections were deferred in 40 cases (7%). These results are in accordance with those of similar studies, and confirm that frozen section is a highly accurate, but not infallible, method of rapid histological diagnosis. PMID- 2330792 TI - Incidence and characteristics of bicycle injuries by source of information. AB - Data from analysis of bicycle injuries in a defined, semirural Finnish population were compared with the national hospital discharge register and official police statistics and were related to national data on prevalence of bicycling. The results suggested an incidence of 7.3 injured persons/1000 population, which was 20-fold the figure derived from the police statistics. Inclusion of injuries treated at health centres doubled the number requiring medical attention. Bicycle injuries accounted for 52% of all traffic injuries. A motor vehicle was involved in 11% of bicycle injuries. In these accidents 18% of the victims were hospitalized, but only 6% in other bicycle accidents. Police and hospital records overestimated the proportion of motor vehicle crashes, involvement of elderly persons and incidence of head injuries and fractures. Non-motor vehicle bicycle accidents accounted for most of bicycle injuries, for 58% of in-patients and 93% of out-patients. Information from all levels of health care is required for injury control. PMID- 2330793 TI - Traumatic rupture of the thoracic aorta. A clinicopathological study. AB - In a county hospital serving a population of roughly 240,000, the hospital records from the period 1982 to 1987 included 27 patients who presented with traumatic rupture of the thoracic aorta. Eighteen patients died instantaneously, one was dead on admission, five died in hospital and three survived operation. Two patients had direct cross clamping of the aorta and Dacron interposition graft soon after admission; both survived. The third patient had a Gott shunt and Dacron interposition graft the day after the accident and survived with paraplegia. In all patients who died in hospital except one, the condition was not diagnosed before death. We conclude that traumatic rupture of the thoracic aorta occurs more frequently than is generally thought. Although most patients die at the scene of the accident, a liberal use of angiography is indicated in all trauma cases admitted to hospital with a history of a forceful deceleration or acceleration injury. PMID- 2330794 TI - Biliary tract surgery: a bacteriologic and epidemiologic study. AB - The sources and routes of postoperative wound infections were prospectively studied in 440 patients undergoing biliary tract surgery. The overall infection rate was 7.3%. Specimens for culture were taken peroperatively from bile, liver bed and subcutaneous fat in 402 patients and also from skin in 64. Of the 126 patients with positive bile culture (31%), all but one had bacteria in the other intraoperative cultures, with high counts of bile bacteria in liver bed and transfer of such bacteria to subcutaneous fat in 81.2%. The wound infection rate in this group was 12.8%. Of the 276 patients with sterile bile, more than 90% had bacteria in the other intraoperative cultures. The degree of contamination was low, with dominance of typical skin bacteria, and the group wound infection rate was 3.2%. In 19 postoperative wound infections intraoperative cultures were available for comparison. Eleven of these infections were classified as endogenous, six as exogenous and two as of uncertain origin. S. aureus was uncommon in bile and intraoperative wound cultures, but was almost as common as E. coli in the etiology of postoperative wound infections, indicating high pathogenicity. PMID- 2330796 TI - Primary torsion of the greater omentum. Case report. AB - Four cases of primary torsion of the greater omentum are reported. The most common clinical picture in this condition mimics acute appendicitis. Primary torsion with spontaneous derotation of the greater omentum may be an important cause of right iliac fossa pain of obscure origin. Scrutiny of the omentum during negative appendiceal exploration is extremely important. Treatment is excision of the twisted, infarcted omentum. PMID- 2330795 TI - Effect of preoperative colonoscopy on the incidence of synchronous and metachronous neoplasms. AB - Colonoscopy and air-contrast barium enema performed preoperatively in 389 patients with colorectal cancer revealed synchronous cancer in 4% and polyp in 14%. Nine of the 16 synchronous cancers were located in other surgical segments than the index cancer, and six of the nine were in stage A or B1. Of the 54 synchronous polyps, 28 were located in such other segments. Half of the synchronous cancers and almost half of the synchronous polyps were missed at double-contrast barium enema. All synchronous cancers and three-fourths of the synchronous polyps were detected at colonoscopy. No patient with preoperative colonoscopy presented with metachronous cancer within 3 years from surgery, and only two were subsequently found to have adenocarcinoma arising from an adenomatous polyp. Endoscopic polypectomy was performed in 21 cases during follow up. Extensive use of preoperative colonoscopy is recommended in the evaluation of colorectal cancer, in order to promote detection of synchronous tumors, reduce the incidence of 'early metachronous' cancer and avoid malignant degeneration of adenomatous polyp. PMID- 2330797 TI - Leiomyoma of the small intestine with giant cyst formation. Case report. AB - A case of small-intestinal leiomyoma presenting as a large intra-abdominal cyst is reported. Cystic degeneration is a common feature of leiomyoma, but presentation of this tumour as a giant cyst is uncommon. PMID- 2330798 TI - Appraisal of myocutaneous flapping for treatment of postmastectomy lymphedema. Case report. AB - Two patients with severe postmastectomy lymphedema of the upper extremity were treated with myocutaneous flapping, using latissimus dorsi muscle. Complete disappearance of edema was achieved by 11 months postoperatively in one case and 50% reduction by 8 months in the other case. The satisfactory results commend the procedure, which has yet to gain global acceptance. PMID- 2330799 TI - Conversion of malfunctioning J pouch to Kock's pouch. Case report. AB - A patient with ulcerative colitis previously treated with restorative proctocolectomy and ileal J-pouch anal anastomosis had recurrent pelvic abscess and poor functional results for 3 years postoperatively. To improve the quality of life, the J pouch was converted to a Kock's pouch. The successful result implies that Kock's continent ileostomy is a good replacement for failed pelvic pouch. PMID- 2330800 TI - Three new primary pelvic carcinomas in a patient following radiotherapy for carcinoma of the cervix. Case report. AB - A 67-year-old woman developed three separate pelvic malignancies forty years after undergoing radiotherapy for a squamous cell carcinoma of the cervix. Although previous exposure to ionising radiation is associated with certain malignancies, review of the literature indicates that there is no strong evidence to support such an association with urothelial or colorectal malignancy. PMID- 2330801 TI - Ruptured aneurysm of the omentum. Case report. AB - A 61-year-old man was operated on for a ruptured aneurysm located on the free margin of the omentum. Such patients should have preoperative arteriography as the source of the haemorrhage can be difficult to find at operation. PMID- 2330802 TI - Intestinal absorption of cationic and anionic ferric colloids and complexes: biochemical, histochemical and morphological observations in rats. AB - This experiment was undertaken to study the possible difference in the intestinal iron absorption efficiency among iron compounds with different electric charges. Observation of rats given oral administration of 59Fe-labeled cationic cacodylate ferric (59Fe-Cac) colloid, anionic citrate ferric (59Fe-Cit) colloid, cationic 59Fe-Cac complex and anionic 59Fe-Cit complex revealed that iron absorption was more efficient in the 59Fe-Cac colloid, moderate in the 59Fe-Cac complex, low in the 59Fe-Cit colloid, and lowest in the 59Fe- cases given 59Fe-Cac colloid and 59Fe-Cac complex, a very high ratio activity was found in the liver and in the erythrocyte or hemoglobin in circulating blood, while the blood plasma, bone marrow, and spleen were low in activity. Histochemical observations of rat jejunal mucosa exposed independently for 10 min to the Fe-Cac colloid, anionic Fe Cit colloid, and Fe-Cac and Fe-Cit complexes revealed that the cationic Fe-Cac colloid and Fe-Cac complex adhered to the luminal surface of the mucosa covering the apical area of villi with some ferric iron in the capillaries, while the anionic Fe-Cit colloid and complex did not adhere to the epithelial cells and were found free in the jejunal lumen. Electron microscopy revealed that Fe-Cac colloid particles were taken into epithelial cells by pinocytosis at the webs of microvilli, moved to the Golgi area, exocytosed to the intercellular spaces, and then translocated into the basement membrane toward blood capillaries. PMID- 2330804 TI - Characterization and induction of a cell line established from a patient with erythroleukemia (FAB M6). AB - A human cell line, designated as NISI, was established from a patient with erythroleukemia (FAB M6). The presence of a chromosome marker in NISI line indicates that it is derived from the leukemic clone which bears the common marker. The cell line shows morphology of immature erythroblast and has myelocytic properties from surface immunophenotyping. The differentiation capacities of NISI cells by three inducers (hemin, phorbor 12-myristate 13 acetate and 1-25-(OH)2D3) were evaluated. Hemin treated cells showed a significant increase in erythroid antigen expression as well as an increase in number of benzidine positive cells. Phorbor 12-myristate 13-acetate treated cells demonstrated a significant increase in megakaryocytic antigen expression, and a slightly diminished CD36 antigen expression. The surface markers of 1-25-(OH)2D3 treated cells did not demonstrate significant changes. NISI cell line, a human erythroleukemia cell line, still retained the tendency for differentiation to megakaryocytic lineage. PMID- 2330803 TI - Mortality of hematopoietic disorders and hair dye use among barbers. AB - A total of 8,316 barbers were followed up from 1976 to 1987 to examine the relations between hair dye use and deaths from hematopoietic disorders. The follow-up rate was about 95%. Three leukemia deaths and two malignant lymphoma deaths were observed in this cohort. The observed deaths were less than the expected number calculated from age- and sex-specific mortality of the general population in Japan (3.8 and 3.0, respectively). No deaths from aplastic anemia or the other hematopoietic disorders were observed. PMID- 2330805 TI - Chemotherapy for acute non-lymphocytic leukemia with low-dose cytosine arabinoside (Ara-C). AB - We administered low-dose cytosine arabinoside (Ara-C) to 32 newly diagnosed acute non-lymphocytic leukemia (ANLL) patients, 10 mg/m2 twice a day for 14-21 days, by subcutaneous injection or continuous intravenous infusion. CFU-GM of bone marrow cells were performed before low-dose Ara-C in some patients. Patients ranged in age from 21 to 78 years old. Ten showed complete remission and 16 partial response. The pretreatment CFU-GM pattern did not reflect the response to low dose Ara-C. The major hematological effect of the treatment was myelosuppression, and most patients required platelet transfusion and the administration of antibiotics. Our study suggested that low-dose Ara-C treatment benefits some ANLL patients. PMID- 2330806 TI - Treatment of chronic granulocytic leukemia in the accelerated phase by transfusion of autologous buffy-coat cells--a case report. AB - We treated a patient with chronic granulocytic leukemia (CGL), in the accelerated phase by intensive chemotherapy followed by the infusion of cryopreserved peripheral blood buffy-coat cells. The cells had been stored for 32 months. The chemotherapy consisted of daunorubicin 40 mg X 2 days, vincristine 2 mg X 1 day, cytosine arabinoside (Ara-C) 200 mg X 6 days and prednisolone 30 mg X 7 days in the first week, then Ara-C 3 g/m2 X 3 days and cyclophosphamide 60 mg/kg X 2 days in the second week, but reversion to the chronic phase was not achieved. Therefore, total body irradiation (TBI) was added to repeated intensive chemotherapy followed by infusion of the remaining cells. Marrow recovery was good. The patient is currently alive and has been in the chronic phase for 22 months. This preliminary result indicates that this therapy may be tried soon after transformation in CGL and that TBI is an important part of therapy in BMT in the accelerated or blastic phase of CGL. PMID- 2330807 TI - A case of chronic myelocytic leukemia in blast crisis: the myeloblasts became overt from lymphoid and myeloid mixed population of the blast crisis cells after chemotherapy. AB - Immunophenotypes and genotypes were analyzed for a case of chronic myelocytic leukemia in blast crisis (BC). In the early stage of BC (early BC), the blasts consisted of lymphoid-myeloid cells, but in the later stage of BC (late BC), they were myeloid cells, morphologically and phenotypically. On Southern blot of DNAs in early BC, a single rearranged fragment of immunoglobulin heavy chain (IgH) genes was detected, whereas IgH genes were in germline configuration in both initial chronic phase and late BC. A clone which had a rearranged IgH gene in early BC, was considered to have co-existed with a clone which had the germline IgH gene. Analysis for bcr genes confirmed that the chronic phase as well as early and late BC were of the same clonal origin. Phenotypic and immunogenotypic analyses, however, revealed that at least two secondary clones emerged from the primary clone. The therapeutic effect against lymphoid population among mixed crisis cells could be evuluated not only phenotypically but also genotypically. PMID- 2330808 TI - Acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase activity of peritoneal neutrophils in patients with terminal renal failure treated by intermittent peritoneal dialysis. AB - Acid phoshatase (AcP), beta-glucuronidase (GR) and N-acetyl-beta-D glucosaminidase (NAG) activity in neutrophils obtained from the peritoneal fluid of 50 patients with terminal renal failure treated by intermittent peritoneal dialysis, and of 30 control subjects with normal renal function was semiquantitatively scored using a cytochemical method. This study was repeated in 22 dialyzed patients during the course of bacterial peritonitis. A significant decrease in the AcP score and an increase in the GR score were found in the neutrophils from dialyzed patients. In dialyzed patients with peritonitis, the GR and NAG scores were higher that in those without this complication. PMID- 2330809 TI - Cancer in myelodysplastic syndromes. AB - Fifty one patients with myelodysplastic syndromes (MDS) treated between September, 1985 and October, 1988 were retrospectively studied. The incidence of cancer was compared with that in the Cancer Registry population of Japan for the same age and sex distribution. In this series, 4 cancers were observed. The risk of cancers developing in patients with MDS was 4.65 times that for an age- and sex-matched population. PMID- 2330810 TI - Taurine in normal and diseased human skeletal muscle. AB - Taurine content of 199 clinical muscle biopsies was determined and correlated to histometric data of 121 cases. Taurine concentration in muscles was markedly dependent on fiber type distribution, taurine being more abundant in the slow, oxidative type 1 fibers than in the type 2 fibers. Taurine concentration rose slightly with age and tended to be higher in denervations, muscular dystrophies and myotonias, but the differences from the control values were non-significant. PMID- 2330811 TI - Neurological complications of brucella spondylitis. AB - Twenty-two patients with brucella spondylitis and neurobrucellosis were studied during a 2-year period. The diagnosis was based on history of exposure, compatible signs and symptoms, high antibody titre and/or positive culture of a clinical specimen(s). Spondylitis was confirmed by plain radiographs, bone scan, CT and in some cases by histology. Neurobrucellosis was confirmed by CSF examination and culture, myelography, NCV, EMG and CT head. The spondylitis was early in 4 cases, chronic active in 12, smouldering "partially healed" in 3 and healed in 3 cases. Of these, 15 patients (68%) had neurological complications of various types. Plain radiographs were not a good index of activity of spondylitis. Tc99 bone scan was not specific and it remained positive long after the completion of therapy. CT was superior in revealing details of bone destruction, soft tissue swelling and entrapment of nerve roots and cord. The 3 modalities were complementary. Spondylitis is commonly associated with neurobrucellosis and symptoms of one may over shadow those of the other and in some cases neurobrucellosis may be subclinical. In all cases of spondylitis, a thorough search for neurobrucellosis should be made and vice versa. Prolonged treatment with a combination of 3 anti-brucella drugs is recommended and prolonged follow-up is necessary. PMID- 2330812 TI - Striatal kinetics of [11C]-(+)-nomifensine and 6-[18F]fluoro-L-dopa in Parkinson's disease measured with positron emission tomography. AB - The kinetics in brain of the dopamine reuptake blocking agent [11C]-(+) nomifensine and the L-dopa analogue 6-[18F]fluoro-L-dopa were compared in 3 patients with idiopathic Parkinson's disease and age-matched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nucleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-[18F]fluoro-L-dopa utilization and [11C]-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinson's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. PMID- 2330813 TI - Multiple sclerosis and other immunologic diseases. AB - A characteristic feature of immunologic diseases is their association with each other. For multiple sclerosis (MS), several retrospective studies reported increased as well as expected coincidence rates with other immunologic diseases. We conducted a prospective case-control study of MS patients and healthy volunteers and found 13/101 MS patients and 2/97 controls with such diseases (P = 0.009, chi-square test), as well as 47/88 MS patients versus 31/95 controls with a variety of circulating autoantibodies (P = 0.004, chi-square test). These results speak for an increased coincidence of MS with other immunologic diseases and support the idea that MS is also an immunologic disease. PMID- 2330815 TI - Parenteral administration of GM1 ganglioside to presenile Alzheimer patients. AB - The pharmacokinetic parameters of GM1 ganglioside were examined in 16 patients (mean age 64 +/- 5 years) with Alzheimer's disease. The ganglioside was given intramuscularly and subcutaneously. The maximum GM1 blood level was reached after 48-72 h, the subcutaneous route leading to the highest blood levels, but the individual variability was relatively large. When 100 mg GM1 ganglioside was given daily for a week, maximum serum values of 15 to 20 mumol/l were found in 3 patients. The elimination half-life from serum was 60-75 h. PMID- 2330814 TI - Epidemiology of multiple sclerosis in northern Greece. AB - A total of 638 new cases of multiple sclerosis (MS) (365 females, 273 males) were found from 1970-1984 in northern Greece (Macedonia and Thrace); the average annual incidence rate was 1.79 per 100,000 inhabitants with increasing incidence from 1980-1984. A total of 729 people living in northern Greece suffered from MS on December 31, 1984 (prevalence rate 29.5 per 100,000 inhabitants). No difference was found between urban and rural areas. No difference from the international standards was found for sex incidence. The study confirms the quite high prevalence of MS despite the fact that northern Greece is in the intermediate risk zone. PMID- 2330816 TI - Ophthalmoplegic migraine: diagnostic criteria, incidence of hospitalization and possible etiology. AB - Charts from patients admitted from April 1976 to March 1986 to the departments of neurology, neurosurgery, ophthalmology and pediatrics serving a population of 615,000 inhabitants in Copenhagen County were surveyed. We then examined patients with coexisting headache and ophthalmoplegia at follow-up. Many diseases may mimic a single attack of ophthalmoplegic migraine. We found 4 cases of ophthalmoplegic migraine, i.e. an annual incidence of 0.7 per million inhabitants. We added another 4 cases from the same area, but diagnosed before or after the study period. Only in 2 of the 8 cases did the ophthalmoplegic episodes fulfil criteria for pain and associated symptoms required for migraine without aura (common migraine). In contrast, the clinical characteristics of the attacks are typical of the Tolosa-Hunt syndrome. When this inflammatory disease strikes a migraineur it is likely to elicit headache with migrainous features. We postulate that such cases have been diagnosed as ophthalmoplegic migraine, whereas the proper diagnosis of Tolosa-Hunt syndrome has been made in non-migraineurs. PMID- 2330818 TI - Epidemiological chronorisk of stroke. AB - A retrospective study was undertaken on onset of symptoms in 667 cases of stroke. All strokes occurred out of hospital. There were 382 males and 285 females, observed from 1971-1988. The 667 cases of stroke consisted of 508 cases of cerebral infarction and 159 cases of cerebral hemorrhage. The data, analyzed by the single cosinor method, demonstrate a significant circadian, circaseptan, and circannual rhythmicity in the occurrence of stroke. The peaks occur in the morning hours, in the weekend, and in winter. Cerebral hemorrhages do not have a circadian rhythmicity in their occurrence, while they do present circaseptan and circannual rhythmicity. Cerebral infarctions present circadian, circaseptan, and circannual rhythms. No difference was found between males and females. The possible factors involved in temporal distribution of stroke are discussed. These observations could be useful for a better understanding of the pathogenesis and treatment of stroke. PMID- 2330817 TI - Do single right hemisphere infarcts or transient ischaemic attacks result in aprosody? AB - The ability to perceive and express prosodic qualities of speech was tested in 21 patients with a single focal ischaemic disturbance of the right hemisphere, 14 patients having an infarct and 7 transient ischaemic attacks, and in 21 age matched normal controls. All patients were predominantly right-handed. None showed signs of aphasia. Pure tone audiometry showed acceptable hearing for speech. The cerebral lesions were assessed by clinical neurologic examination, and by CT, EEG and measurement of regional cerebral blood flow (rCBF) using intravenous 133-xenon. The prosodia test included items testing: the ability to perceive accentual and emotional qualities of speech, and the ability to express and vary such qualities. The test did not discriminate between the patients and the controls, although some patients had large right-sided lesions. This negative finding indicates that aprosody in patients with brain lesions appears more difficult to detect than has previously been assumed. Highly sensitive tests are most likely required. PMID- 2330819 TI - Neuropsychological findings in treated Wilson's disease. AB - Seventeen patients, treated for Wilson's disease (WD), underwent a set of neuropsychological tests and were compared with a closely matched control group. There were clear differences between the groups (chi 2-test, p less than 0.0001). Wilson patients with only hepatic involvement, however, did not at all differ from their controls. Wilson patients with neuropsychiatric signs differed from controls on a reasoning test (p = 0.0016), and the entire WD group differed on a perceptual speed task (p = 0.0025). Compared to normal test values, however, the patients' group means were all within plus or minus one standard deviation from the normal mean. Special testing procedures and construction of the test battery excluded a factor of motor deficits as a major cause for the differences. The neuropsychological findings are viewed in relation to other findings in patients with motor disorders and predominantly subcortical lesion sites. Wilson's disease may be a dementing condition, but not when treated adequately. PMID- 2330820 TI - A case of anorexia nervosa with acute renal failure resulting from rhabdomyolysis. AB - Symptoms of acute renal failure were observed in an anorexia patient who had a history of frequent vomiting. The acute renal failure might have resulted from rhabdomyolysis subsequent to a disturbance of electrolyte balance. This acute renal failure might have resulted in death if not treated. We postulate that even a mild case of anorexia nervosa should be carefully observed to prevent such possible tragedy. PMID- 2330821 TI - Serum lipoprotein pattern variations in dementia and ischemic stroke. AB - Blood levels of triglycerides, total cholesterol, isolated lipoprotein fractions (VLDL-LDL- and HDL-cholesterol) and apoproteins (Apo-A1 and Apo-B) were examined in multi-infarct dementia, senile dementia of the Alzheimer type, ischemic stroke associated with carotid atherosclerosis and in control subjects. Forty patients divided into 10 consecutive patients for each group were studied. Alzheimer patients showed mean total cholesterol and Apo-B values significantly higher than control subjects. Apo-B was significantly higher in stroke patients than in controls. The mean lowest HDL-cholesterol (HDL-c) value was observed in stroke patients. No significant differences in mean HDL-c levels were found between patients with multi-infarct and Alzheimer dementia. PMID- 2330822 TI - Neurotrophic effect of vasoactive intestinal polypeptide (VIP) on the ventral spinal cord of rat embryo. PMID- 2330823 TI - Plasma 3-methoxy-4-hydroxyphenylglycol in manic patients: relationships with clinical variables. AB - Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were found to be significantly higher in manic patients than in age- and sex-matched normal controls (n = 22). In 18 manic patients plasma MHPG correlated with manic symptoms but not with anxiety, depression, motor behaviour, acute psychosis, schizophrenia and severity of illness. A positive correlation between MHPG and grandiosity items on rating scales suggests a link with cognitive contents and therefore a relationship with central factors. PMID- 2330824 TI - Suppressant effects of dexamethasone on the availability of plasma L-tryptophan and tyrosine in healthy controls and in depressed patients. AB - Formation in the brain of serotonin from L-tryptophan (L-TRP) and noradrenaline from tyrosine are pathways related to the pathophysiology of major depression and to the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In the past, decrements in L-TRP availability and disorders in the HPA axis have repeatedly been observed in major depressed patients; both factors were shown to be inversely correlated. In order to investigate the relationships between glucocorticosteroid activity and the availability of L-TRP and tyrosine, the authors measured L-TRP, tyrosine, valine, leucine, isoleucine and phenylalanine in baseline conditions and after treatment with 1 mg dexamethasone in 16 healthy controls and in 50 depressed patients. The ratios between L-TRP and tyrosine and the sums of the amino acids known to compete with them during transport across the blood-brain barrier were computed as an index of (respectively) the serotonin and noradrenaline synthesis in the brain. We found significantly decreased plasma L-TRP and tyrosine levels after treatment with dexamethasone compared with basal levels. Accordingly, the plasma ratios between L-TRP and tyrosine and the sum of the competing amino acids were significantly reduced by dexamethasone administration. It was hypothesized that through these actions of dexamethasone on peripheral amino acids, the central noradrenaline and serotonin control over the HPA-axis could be altered. PMID- 2330825 TI - The effects of total sleep deprivation and subsequent treatment with clomipramine on depressive symptoms and sleep electroencephalography in patients with a major depressive disorder. AB - In the present study patients with a major depressive disorder were first subjected to total sleep deprivation (TSD) and then treated with clomipramine. Sleep electroencephalography (EEG) was registered prior to and after TSD, during the 2 initial nights of antidepressive treatment and after 19 days. A negative correlation between response to TSD and clomipramine was found. TSD did not differentially influence the sleep EEG (responders vs nonresponders): responders tended, however, to show a more classical depressive sleep pattern prior to TSD. Clomipramine profoundly suppressed rapid eye movement (REM) sleep; the amount of initial REM sleep reduction, however, did not correlate significantly with therapy response after 3 weeks of treatment. PMID- 2330826 TI - Gender differences in initiation of psychotherapeutic medicine use. AB - It has been shown that women are more likely than men to have used prescription psychotherapeutic medicines. Gender differences in the determinants of such use have also been identified. In an earlier study of adult household residents aged 18-44, we found that antecedent illicit drug use was associated with prescribed psychotherapeutic medicine use, independent of psychiatric symptoms. In this study, we explore these predictive relationships separately for males and females. For both males (n = 604) and females (n = 933) illicit drug use was associated with psychotherapeutic medicine use, although the relationship was stronger among males. Psychiatric symptoms did not account for this relationship for either gender. Among males, symptoms and illicit drug use each increased the likelihood of psychotherapeutic medicine use. Among females, no additional likelihood of psychotherapeutic medicine use over and above that for illicit drug use resulted when psychiatric symptoms were also present. Help-seeking was strongly associated with prescription psychotherapeutic medicine use among both genders. PMID- 2330827 TI - A 30-year follow-up study of a child psychiatric clientele. I. Demographic description. AB - A register investigation was carried out as of December 31, 1980, with the aim of giving a broad description of a child psychiatric clientele 30 years after admission to hospital. The material consists of 322 patients--189 boys (59%) and 133 girls (41%)--who were admitted during the period 1949-1951 to the only 2 child psychiatric departments at that time in Denmark. We succeeded in identifying 93% of the patients. The mean age at the time of analysis was 38.6 years (range 32-46). The material was compared with the age-related Danish population by marital status, vocational education, and socioeconomic class. A total of 115 patients (36%) had been admitted to an adult psychiatric department, and 50 patients only once. A total of 95 patients (30%) had committed criminal offences and 12 had only committed traffic offences. A total of 60 patients (19%) had obtained disability pensions. During the 30-year follow-up period, 19 patients (6%) had died. A statistically significant extra mortality was found only for women. Four patients had committed suicide. By logistic regression analysis, a statistically significant correlation was found between criminal record and admission to psychiatric department and the variables: divorce, no vocational education, and lowest socioeconomic class. About 54% had managed well, judging by the variables employed. PMID- 2330828 TI - A quantitative study of nursing staff interactions in psychiatric wards. AB - Data from 2 studies investigating staff-patient and staff-staff interaction rates are presented. In the first the staff-patient ratio was varied by holding patient numbers constant and systematically varying staffing levels. The results showed that although the percentage of time nurses spent interacting with patients did not change, staff-staff interaction increased as a function of increased staffing levels. In the second study the interaction rates from 4 wards were combined. These data showed that, as in the first study, staff-patient interaction remained constant, as staff numbers increased, whilst staff-staff interaction increased. However, unlike the first study, when analysed in terms of the staff-patient ratio, both categories of interaction increased as the staff-patient ratio increased. PMID- 2330829 TI - Premenstrual anxiety and depression: comparison of objective psychological tests with a retrospective questionnaire. AB - Increased anxiety and depression are among the most frequently reported psychological problems in women seeking help for severe symptomatic premenstrual change, but there has been little objective evaluation of these symptoms. We therefore examined the results of objective psychological testing in 40 women with no apparent psychiatric or psychological disorder who had reported moderate to extreme increased anxiety and depression on a retrospective assessment form. Scores on the State-Trait Anxiety Inventory and Institute of Personality and Ability Testing (IPAT) Depression Scale increased from the low symptom intermenstrual phase of the cycle (days 5-10) to the premenstrual phase (within the last 6 days of the cycle), suggesting that retrospective complaints of increased premenstrual anxiety and depression can be confirmed on objective psychological assessment. However, it was observed that the distribution of intermenstrual IPAT depression scores was bimodal. Cyclic changes varied among the tests depending upon the IPAT depression score. The study suggests that 2 populations may exist in this screened sample; one population appears to have "pure PMS" and the second groups manifests a premenstrual exacerbation of subclinical depression. PMID- 2330830 TI - Serum creatine kinase BB isoenzyme levels in an epidemiological study of dementia and cognitive impairment. AB - It has been suggested that serum creatine kinase levels might be useful in the investigation of dementia. In this study serum creatine kinase BB (CKBB) isoenzyme levels were investigated in a community population of elderly women aged 70 to 80 years. Normative data for this group were compared with the findings in younger age groups. No relationship was found between levels of CKBB and level of dementia, or with the specific clinical diagnosis of senile dementia of the Alzheimer type, although a weakly positive relationship was found between CKBB and 3 cognitive scales. PMID- 2330831 TI - Coding guidelines for ICD-9 section on mental disorders and reliability of chart clinical diagnoses. AB - A major innovation of the ICD-10 draft is provision of diagnostic guidelines. This is assumed to be appropriate for use in clinical situations. In Norway a similar approach was adopted when ICD-9 was introduced as the official classification system in 1987. This was done in order to avoid national diagnostic bias and increase diagnostic reliability. A comparison with the DSM III criteria was included in the diagnostic guidelines. The effectiveness of this approach was investigated by comparing the chart ICD-9 diagnoses of 104 psychiatric in- and outpatients from 2 teaching hospitals with the diagnoses obtained by using case record rating forms (criterion diagnosis). According to the criterion diagnoses, the base rate of chart diagnoses of schizophrenia and manic-depressive psychosis was too low, and the base rate of reactive psychosis too high. Several chart diagnoses proved to have low reliability, particularly reactive psychosis, paranoid psychosis, depressive neurosis and personality disorders. The study suggests that the provision of extensive diagnostic guidelines does not necessarily alter previous diagnostic practice. Reasons for these findings and the implications for the ICD-10 diagnostic criteria and diagnostic guidelines are discussed. PMID- 2330832 TI - Platelet serotonin decrease in alcoholic patients. AB - This study investigated the platelet 5-HT levels and their changes according to different physiological and pathological factors in 30 young alcoholic patients (16 alcohol abusers and 14 alcohol-dependent subjects) and 26 healthy controls. Platelet 5-HT levels were determined by a fluorescent-ortho-phthalaldehyde assay. The mean platelet 5-HT levels obtained in patients during withdrawal and after 2 weeks of abstinence were significantly lower than in controls. Presence of positive history of impulse control disorders (ICD) influenced the mean platelet 5-HT levels in patients. These preliminary results suggest that the platelet 5-HT level decrease observed in alcohol-dependent patients mostly free from ICD and in alcohol abusers mostly affected by ICD might result from comparable neurobiological mechanisms. However, the age of onset of alcohol dependence might depend on psychological functioning features. PMID- 2330833 TI - Blood platelet monoamine oxidase activity, serotonin uptake and release rates in anorexia and bulimia patients and in healthy controls. AB - Platelet monoamine oxidase (MAO) activity, serotonin uptake rate and serotonin efflux rate have all been suggested to be markers for central serotonergic mechanisms. Platelet MAO activity is associated with certain personality traits, with low activity linked to traits such as impulsiveness, sensation-seeking and avoidance of monotony, all possible expressions of low central serotonergic activity. Low platelet serotonin uptake rate has been connected to unipolar depression and the rate of efflux, in the presence of the ATP uncoupler CCP, higher in bipolar depressives than in controls. Platelet MAO was found to be lower in 16 consecutive female inpatients fulfilling the DSM-III criteria for bulimia nervosa than in 12 female controls. Rates of serotonin uptake and efflux in the presence of CCP were, on the other hand, similar to the controls. In the controls there were no correlations between platelet MAO activity and any of the other parameters estimated. Vmax for the platelet uptake of serotonin correlated positively with the Km for the uptake, but not with any other parameter. The uninfluenced rate of efflux of serotonin correlated positively with the efflux in the presence of the ATP uncoupler CCP. PMID- 2330834 TI - A follow-up study of dementia diagnosed in the community using the Cambridge Mental Disorders of the Elderly Examination. AB - Elderly Cambridge residents diagnosed as demented using the Cambridge Mental Disorders of the Elderly Examination (CAMDEX) were reviewed approximately 12 months later. Diagnoses were confirmed in 133 of 137 surviving cases (97%). Subjects said to have minimal dementia (cognitive impairment insufficient to warrant a diagnosis of dementia proper) had a varied outcome. Only 6 out of 29 survivors showed progressive intellectual deterioration and 13 were reclassified as normal. Subjects passed as normal in the first year of the study were reviewed using the Mini-Mental State Examination. We cannot be certain how many were actually dementing, but our findings suggest that only a small number of false negative diagnoses were made in the first year of the study. PMID- 2330835 TI - Physical illness and depression: the effects of acute physical illness on the mental state of psychiatric inpatients. AB - A patient is described with a severe agitated depression who made a dramatic recovery following an acute myocardial infarction. A retrospective case notes study was conducted to investigate the effects of a sudden physical illness on the mental state of a group of psychiatric inpatients. Seven patients were identified with agitated depression who improved considerably following an acute life-threatening physical event. Patients with other forms of depression, schizophrenia and schizoaffective disorder showed either no change or underwent a deterioration in mental state. PMID- 2330836 TI - Effect of clomipramine on premenstrual syndrome. AB - Clomipramine (25-50 mg) was administered daily for 5 consecutive menstrual cycles to 5 nondepressed women with severe premenstrual irritability and sadness. All subjects reported a dramatic reduction in premenstrual complaints. PMID- 2330837 TI - The prognosis in early adulthood of child psychiatric patients: a case register study in Denmark. AB - A register-based study of 485 children (0-15 years of age) admitted to a child psychiatric hospital from January 1, 1970 to December 31, 1972 who were followed up on December 31, 1986 showed higher rates of admission to psychiatric hospital in late adolescence or young adulthood (i.e. greater than or equal to 16 years of age) than found in an age-standardized general population. Patients with the childhood diagnosis neurosis (ICD-8 300 + 308.00) were found to have higher rates of admission with personality disorders (ICD-8 301.09-301.39 + 301.82-301.99) but not of other diagnoses including neurotic disorders. Patients with the childhood diagnosis of conduct disorder (ICD-8 301.09-301.99 + 308.01) had a higher risk of admission in adulthood with the diagnosis of personality disorders and drug or alcohol abuse. Girls with adjustment disorder (ICD-8 307 + 308.02-308.06) had higher risks of admission in young adulthood with diagnosis of personality disorders and psychosis. No connection was found between the age at first referral and the incidence of admission after the age of 15 years. PMID- 2330838 TI - Heart rate and blood pressure changes during postural change and isometric handgrip exercise in patients with panic disorder and normal controls. AB - Changes in heart rate (HR) and blood pressure (BP) were measured serially during postural changes and isometric hand grip exercise test (IHT) in 30 patients with panic disorder and 30 normal controls. Though there were no significant differences in the delta increase of HR or systolic or diastolic BP during these tests, the resting supine and standing diastolic BP were significantly higher in panic disorder patients than in controls. The standing mean BP was also significantly higher in panic disorder patients. These findings are suggestive of an increase in adrenergic tone in panic disorder patients. PMID- 2330839 TI - Dopaminergic supersensitivity and vomiting among schizophrenic patients. AB - The prevalence of vomiting among schizophrenic inpatients was determined over a 6 week period; 8 of 19 patients (42%) experienced at least one episode of vomiting and 3 (16%) experienced 4 episodes. A hypothesis that this may be a dopaminergic supersensitivity phenomenon is proposed, but no association with tardive dyskinesia, another putative supersensitivity phenomena, could be demonstrated. The authors suggest that vomiting among schizophrenic patients is usually underestimated and may at times be a serious clinical problem. PMID- 2330840 TI - Cognitive and emotional improvement in a group of dementia patients. PMID- 2330841 TI - In vivo analysis of extracellular proteins in rat brains with a newly developed intracerebral microdialysis probe. AB - Peptides and proteins in the extracellular space in the central nervous system were investigated in vivo using an intracerebral microdialysis probe. The molecular cut-off of the hollow fiber which was used for the probe was approximately 100 kDa. We examined recovery rates of several compounds in vitro. The recovery rates of proteins and peptides were between 7-28%, with the exceptions of substance P and insulin-like growth factor I. The recovery rates of monoamines and their metabolites were 22-40%. In in vivo studies, two major proteins with apparent molecular weights of 62 kDa and 12 kDa, and several minor proteins (28 kDa, 43 kDa, 52 kDa and 70 kDa) were detected by SDS-polyacrylamide gel electrophoresis in the dialysate from a probe implanted in the striatum of anesthetized rats. These results suggest that the newly developed, intracerebral microdialysis probe might be useful for investigating the dynamic changes of peptides and proteins in the central nervous system. PMID- 2330842 TI - Role of endogenous prostaglandin E2 in interleukin 1 production by peripheral blood monocytes from patients with rheumatoid arthritis. AB - We studied the effect of endogenous prostaglandin E2 (PGE2) on interleukin 1 (IL 1) production by peripheral blood monocytes from patients with rheumatoid arthritis (RA). IL-1 production by RA monocytes was not different from that of monocytes from normal controls, when the cells were either unstimulated or stimulated with lipopolysaccharide (LPS, 20 micrograms/ml), as measured by two different bioassays (thymocyte or fibroblast proliferation assay) and enzyme linked immunosorbent assay. However, IL-1 production by LPS-stimulated monocytes from RA patients cultured in medium containing indomethacin, an inhibitor of PGE2 synthesis, was significantly greater than that of monocytes from normal controls. In addition, the levels of PGE2 in culture supernatants of unstimulated or LPS stimulated monocytes from RA patients were higher than in culture supernatants of monocytes from normal controls. Moreover, the increase of in vitro IL-2 production by RA T cells stimulated by phytohemagglutinin (PHA) was observed when monocytes were removed from peripheral blood mononuclear cells. These results indicated that peripheral blood monocytes from RA patients could produce IL-1 in excess in vitro, but that in vivo IL-1 production by RA monocytes and IL-2 induction by RA T cells might be negatively regulated by endogenous PGE2. PMID- 2330843 TI - Ultrastructural localization of endogenous peroxidase activity in Hashimoto's thyroiditis. AB - Ultrastructural localization and intensity of endogenous thyroid peroxidase (TPO) in Hashimoto's thyroiditis were examined in relation to the serum thyroid hormone level, thyroid-stimulating hormone (TSH) concentration and anti-thyroid autoantibody titer. In Hashimoto's thyroiditis, TPO activity on the microvilli of follicular cells was more intense than that of normal thyroid tissue, but the intensity of the intracytoplasmic peroxidase reaction was generally weaker than that of Graves' or normal thyroid tissue. Microvillar TPO reaction products were positive in all thyroid follicular cells in patients with increased TSH levels, but no TPO activity was observed on the microvilli of patients with normal or low TSH levels, irrespective of their histological type or serum anti-microsomal antibody titer. It is suggested that TPO activity on the surface of microvilli of thyroid follicular cells in Hashimoto's thyroid gland is modulated by thyrotropin but is not affected by anti-thyroid autoantibodies. PMID- 2330844 TI - Effects of HR-592, a new derivative of indole, on conditioned behavior. AB - Effects of HR-592, a new derivative of indole, on conditioned avoidance and intracranial self-stimulation behavior were investigated in rats using a shuttle box and a Skinner box, respectively. The oral administration of HR-592 at doses of 3-10 mg/kg caused a dose-dependent suppression of the conditioned avoidance response. Even the escape response was slightly suppressed in the group administered 10 mg/kg of HR-592. The self-stimulation behavior was suppressed dose-dependently from 1 to 8 h after the administration of 6-10 mg/kg of HR-592. These results indicate that the action of HR-592 on conditioned avoidance response and intracranial self-stimulation behavior is similar to the action of neuroleptics. PMID- 2330845 TI - Determination of hypotaurine and taurine in blood plasma of rats after the administration of L-cysteine. AB - A method for the simultaneous determination of hypotaurine and taurine was developed. The method consisted of the elimination of urea, which interfered with the determination of hypotaurine, by immobilized urease, and determination of hypotaurine and taurine with an amino acid analyzer. The analyzer equipped with a cation-exchange column was operated at 32 degrees C with 0.2 M sodium citrate buffer, pH 2.8. Using this method, the dynamics of hypotaurine and taurine in blood plasma of rats was studied after the intraperitoneal injection of L cysteine. The concentration of cysteine reached the maximum 1 h after L-cysteine loading. The concentration of hypotaurine and taurine increased in parallel and reached the maximum 2 h after L-cysteine loading. These changes seem to indicate the precursor-product relationship of these substances and the rapid conversion of hypotaurine to taurine in vivo. PMID- 2330846 TI - Influence of emotional stress on pharmacokinetics of isosorbide dinitrate intraperitoneally administered to rats. AB - The plasma level of isosorbide dinitrate intraperitoneally administered to rats stressed by foot-shock was almost the same as that in non-stressed control rats. However, levels of its metabolites, 5-isosorbide mononitrate and 2-isosorbide mononitrate, were lower in stressed rats than in non-stressed rats, suggesting that stress may influence the metabolism and/or excretion of the metabolites. PMID- 2330847 TI - [The distinctive quality of depressed mood. III: Factorial structure of the pathologic sadness index]. AB - The authors report results of a factor analysis on a Pathological Sadness Index. The rate of total variance accounted (construct validity) is a 55% and two factors are found: distinct quality and rise-bodied. PMID- 2330848 TI - [Personality and aggressiveness in cancer patients]. AB - The authors studied the Personality and Aggressiveness of fifty-three cancer patients by using MMPI and the Instrument I for the Aggressiveness Measurements. The common characteristics in all of then were that they suffered solid tumors, were submitted to hospital treatments and had an absence of psychiatric illness in their personal history. Among the results that stand out most is the sensations of change that the patients experience due to their own illness, the hospitalization and the treatments which they undergo. There exists on increase of self-aggressiveness or a decrease of hetero-aggressiveness which predominates the scales of depression and social introversion, with a decrease of inner strength. In any case, the neuroticism and the dependence are increased and there are decreases in the scales of psychopathic deviation and domination. The four psychosis is staying normal, the hysteria is decreased in men and the hypochondria is increased in women. The defence mechanism that predominates are the denial and the avoidance reaction. PMID- 2330849 TI - [Neuropsychological exploration in dementia: presentation of a neuropsychologic battery in the study of Alzheimer's disease]. AB - The neuropsychological battery PIENC-BARCELONA-86, in experimental phase, is being presented. The study is being done with 37 patients with Alzheimer's disease and 37 control subjects. The selection of the battery's subtests that differ more significantly the pathologies from the control subjects, give us a neuropsychological outline typical in dementia patients and specially in the Alzheimer's disease. The sensitivity and specificity of this battery is of a 67.6% and 92.6%, respectively, that improves up to 100%, when you differ inside the pathological group two subgroups: mild and moderate. PMID- 2330850 TI - [Psychopathologic aspects of cancer in gynecology. Cancer of the breast]. AB - We study 31 female patients diagnosed and treated with the usual method for breast cancer. We use the clinical report and psychobiography, Instrument I to measure the aggressivity and M.M.P.I. The most significant results are: slowness in the first examination, influence of psychosomatic life events and spontaneous signs during the interviews, increase of autoaggressivity, and raising of the neurotic triad, dependence and introversion. It is clear from this statement the general conclusion of this patients having a want of contact so that their psychological signs don't develop into psychopathological. PMID- 2330851 TI - [Stress reactivity index-32 in a student population]. AB - We present here the preliminary results of the 32-item version of the reactivity to stress questionnaire. The sample consisted of 84 medical students. The mean score was 9.9. There were no sex difference in the total reactivity to stress index score or in any of the subscales. PMID- 2330852 TI - Augmenting the narrow-based breast: the unfurling technique to prevent the double bubble deformity. AB - Routine subpectoral or subglandular mammary augmentation in women with a small breast (particularly lower pole deficiency) often results in poor late results with the appearance of a double-bubble deformity. We describe our experience with a technique of unfurling the breast tissue at augmentation in an effort to avoid this complication and improve the long-term results. PMID- 2330853 TI - Correction of abnormally high nipples after reduction mammaplasty. AB - One of the most common complications after reduction mammaplasty is the abnormally high location of the nipple. The deformity may appear immediately after surgery if there was faulty planning before or during surgery. Or it may appear a few months after surgery due to migration of the breast tissue downward as a result of gravity, leaving the relatively fixed nipples at a higher location. This is more pronounced in cases of gigantic breasts and in virginal hypertrophy of the breast. The purpose of this article is to describe an alternative technique for correction of the highly located nipple. PMID- 2330854 TI - Mammaplasty: shape, volume, and scar size. AB - Recently many mammaplasty techniques have been presented with special attention paid to the resulting scar's size and its position. The surgeon should try to hide the scar, and if the inverted T incision is used, its horizontal branch should be as short as possible and kept in the breast area. Nevertheless, excessive concern about the final scar size should not interfere with the final results of the mammaplasty as far as shape, volume and lasting results are concerned. The author presents his experience in mammaplasty with respect to the volume, the shape, and the scar size interrelationships. PMID- 2330855 TI - Analysis of 60 cases of simultaneous mammaplasty and abdominoplasty. AB - The authors report 60 cases of simultaneous breast and abdomen reduction and analyze the value of its use. The combined procedure remodels the body contour with excellent results and low morbidity. PMID- 2330856 TI - The callous elbow and aging of the upper arm. AB - The author describes his surgical approach to the problems of the aging upper arm and elbow region. Surgery at an appropriate age can prevent the progressive wrinkling of the elbow which is further aggravated by aging of the upper arm. The author's operation is aimed at correcting both portions of the arm anatomy at the same time. PMID- 2330858 TI - Sustained beneficial effects of gallopamil (D600) on size of myocardial infarction 24 hours after coronary artery occlusion in dogs. AB - To examine whether gallopamil (D600), a methoxy derivative of verapamil, has sustained beneficial effects on the ischemic myocardium, its effects on the size of myocardial infarction determined 6 hours (protocol 1) and 24 hours (protocol 2) after left anterior descending coronary artery occlusion were compared in anesthetized, open-chest dogs. To quantify the extent of the hypoperfused zone, Tc-99m- or In-111-albumin microspheres were injected into the left atrium 1 minute after occlusion. Fifteen minutes after occlusion, dogs were randomly assigned to a control group or a gallopamil-treated group that received immediately after assignment 0.08 mg/kg of gallopamil followed by a continuous infusion of 0.2 mg/kg/hr for 6 hours. Six or 24 hours after occlusion, the left ventricle was cut into 3 mm thick slices for triphenyltetrazolium chloride staining and autoradiography. There were no differences in the extent of the hypoperfused zone among the four groups. In both protocols 1 and 2 the ratio of the extent of myocardial necrosis to the extent of the hypoperfused zone was significantly smaller in the treated groups (56.7 +/- 6.7% [n = 8], p less than 0.01 and 72.3 +/- 5.3% [n = 6], p less than 0.05 for protocols 1 and 2, respectively) than in the control groups (100.7 +/- 6.0% [n = 7] and 95.2 +/- 4.3% [n = 5] for protocols I and II, respectively). Thus gallopamil administered early after coronary artery occlusion had beneficial effects on the ischemic myocardium, which were sustained for at least 24 hours after the onset of infarction. PMID- 2330857 TI - Patients seeking symmetrical recontouring for "perceived" deformities in the width of the face and skull. AB - This article describes plastic surgery patients who sought symmetrical recontouring of the width of the face and skull. The basic demographic and personality characteristics of these facial width deformity (FWD) patients and the surgical procedures performed on them are discussed. Details of the surgical and psychological management of three representative cases are given. Speculative conclusions regarding the general characteristics of the FWD population are offered. Suggestions are proposed for a combined surgical-medical psychotherapeutic collaboration in managing these patients. PMID- 2330859 TI - Factors associated with late onset of advanced atrioventricular block in acute Q wave inferior infarction. AB - To elucidate the clinical characteristics associated with advanced atrioventricular (AV) block that appears relatively late (more than 24 hours) after the onset of myocardial infarction (MI), 101 patients with acute Q wave inferior MI were studied. Fourteen patients had late-onset advanced AV block, and 87 patients were free of AV block. The hospital mortality rate was 11%. Multivariate analysis was performed to determine the important variables associated with the occurrence of late advanced AV block and hospital mortality rates based on 12 clinical variables. Colloid osmotic pressure, right atrial pressure, serum potassium level, and number of segments with advanced asynergy were the significant factors associated with the occurrence of late advanced AV block, whereas advanced asynergic segments and alveolar arterial oxygen difference were important in the consideration of hospital mortality rates. Therefore not only the extent of myocardial ischemia but also the increases in the extracellular potassium level and interstitial fluid are some of the factors that are associated with the occurrence of late advanced AV block in acute inferior MI. Late advanced AV block, in itself, has no significant influence on hospital mortality rates. PMID- 2330860 TI - Reentrant ventricular arrhythmias in the late myocardial infarction period: 17. Correlation of activation patterns of sinus and reentrant ventricular tachycardia. AB - The relationship between myocardial sites with late activation during sinus rhythm and sites critical for the initiation and sustentation of reentrant ventricular tachycardia was systematically examined in the 4-day-old postinfarction canine heart. The critical sites for prevention of the initiation of reentry and for termination of sustained figure-of-8 reentrant tachycardia by cryothermal techniques were correlated with the last 20 msec isochrone during sinus rhythm. In 12 experiments, 20 critical sites were examined. The mean distance between sites critical for reentry and the latest isochrone during sinus rhythm was 26.7 +/- 13.3 mm. Only five sites (25%) were within a 12 mm distance, which corresponded to the diameter of the cryoprobe. Nine sites (45%) were within a 24 mm distance (twice the diameter of the cryoprobe), while 11 sites (55%) were separated by more than 24 mm. In three experiments the sites of latest activation during sinus rhythm represented areas showing Wenckebach period or 2:1 conduction block. These sites became dissociated and did not participate in the reentrant excitation induced by premature stimulation. Poor correlation was explained by the fact that sites critical for reentry were intimately related to the location and extent of the arcs of functional conduction block while sites of delayed activation during sinus rhythm were not. PMID- 2330861 TI - Hemodynamic effects of intravenous procainamide during ventricular tachycardia. AB - Radionuclide angiography was used to study the hemodynamic effects of intravenous procainamide during stable monomorphic ventricular tachycardia. In four patients studied without procainamide, the ejection fraction was 25% +/- 2.4% during normal sinus rhythm, dropped to 11.3% +/- 2.2% (p less than 0.05) at the onset of ventricular tachycardia, increased to 16.7% +/- 1.7% after remaining in ventricular tachycardia for 10 minutes, and returned to 25.3% +/- 3.7% in sinus rhythm. In the 10 study patients, ejection fraction dropped from 36% +/- 5.8% in sinus rhythm to 25% +/- 5.1% in ventricular tachycardia (p less than 0.2). Ejection fraction decreased further (23% +/- 5.0%) following low doses of procainamide (140 +/- 52 mg) despite cycle length prolongation (354 +/- 18 msec versus 373 +/- 21 msec, p less than 0.5). In 8 of 10 patients, there was a progressive increase in the ejection fraction (28.8% +/- 4.1%). Ventricular tachycardia onset also resulted in a decrease in cardiac output and end-diastolic and end-systolic volumes. Two patients who tolerated procainamide in sinus rhythm showed hemodynamic collapse secondary to procainamide during ventricular tachycardia. We conclude that in some patients hemodynamic intolerance to an antiarrhythmic drug may only become evident during ventricular tachycardia. PMID- 2330862 TI - Inducible monomorphic sustained ventricular tachycardia in the conscious pig. AB - Sustained monomorphic ventricular tachycardia (VT) is of clinical importance but has not been readily modeled in conscious animals. Eleven pigs had myocardial infarction induced by pulling snares previously placed around the left anterior descending (LAD) coronary artery. Six days after occlusion, bipolar pacing catheters were inserted in the right ventricular apex for induction of VT. Testing was repeated in conscious pigs on 6 out of 8 to 19 days after infarction. Monomorphic VT was induced in each animal during each session, using three to four extrastimuli. VT was terminated by burst pacing in 74% of trials; average VT rate was 362 +/- 26 beats/min. VT was prevented in four of eight animals by procainamide and in five of eight animals by magnesium, but was not prevented by lidocaine or metoprolol. The model may be useful in the study of potentially malignant ventricular tachyarrhythmias, important prodromes for sudden death. PMID- 2330863 TI - Barucainide, a novel class Ib antiarrhythmic agent with a slow kinetic property: electrophysiologic observations in isolated canine and rabbit cardiac muscle. AB - Electrophysiologic effects of barucainide hydrochloride on the transmembrane potentials of isolated canine and rabbit cardiac muscle were investigated by means of a standard microelectrode technique. Barucainide (10(-6) to 3.0 x 10(-5) mol/L) produced concentration-dependent inhibition of the maximum upstroke velocity (Vmax) in canine Purkinje fibers and ventricular muscle. Tonic block of Vmax was small and negligible. Barucainide produced marked use-dependent block (UDB). The onset rate of UDB and the speed of recovery from UDB were comparable to those of disopyramide. The recovery time constant was 8.0 +/- 0.8 seconds. Membrane depolarization induced by high concentrations of potassium enhanced the inhibitory action of barucainide on Vmax. The enhancement of tonic block was much greater than that of UDB indicating a selective effectiveness of the drug in pathologically depolarized tissues. Barucainide produced marked shortening of the action potential duration (APD), which indicates that barucainide exerts class Ib antiarrhythmic effects. Such shortening effects on the APD were not affected by pretreatment with 1 mmol/L cobalt or with 0.5 mmol/L 4-aminopyridine. In contrast, barucainide had no marked effects on the APD in the presence of 4.0 x 10(-5) mol/L lidocaine, although it produced almost the same extent of Vmax inhibition as did barucainide alone. Frequency of the pacemaker activity in the rabbit sinoatrial tissue and of the automaticity at normal resting potential in Purkinje fibers enhanced by 2.0 X 10(-6) mol/L isoproterenol were significantly suppressed by barucainide. However, barucainide up to 3.0 x 10(-5) mol/L failed to suppress the firing frequency of the abnormal automaticity in canine Purkinje fibers induced by 5 mmol/L barium. These overall findings indicate that barucainide is a novel class Ib antiarrhythmic agent which, unlike other Ib agents, has a slow kinetic property. However, the precise significance of this unique electrophysiologic feature with respect to the antiarrhythmic action of the drug is not known but provides the basis for understanding the relationship of electrophysiologic effects of barucainide in vitro and its potential antiarrhythmic actions in experimental animals and in humans. PMID- 2330864 TI - Parasympathetically modulated antiarrhythmic action of lidocaine in atrial fibrillation. AB - Clinical experience has shown that the antiarrhythmic effect of lidocaine on atrial arrhythmias, and specifically for the conversion of atrial fibrillation to normal sinus rhythm, is minimal. This study summarizes our experience in 30 dogs in which atrial fibrillation was initiated and sustained (greater than or equal to 15 minutes) under increased vagal tone achieved by either alpha-chloralose anesthesia (26 dogs) or pentobarbital sodium anesthesia combined with direct external electrical vagal stimulation (four dogs). Under increased vagal tone (regardless of the procedure), an intravenous bolus of lidocaine (2 to 3 mg/kg) was 100% effective (101 of 101 episodes) in pharmacologically converting atrial fibrillation to normal sinus rhythm. This was associated with marked slowing of intra-atrial electrical activity, as shown by fast Fourier analysis of intra atrial electrograms. Over a period of 3 to 5 minutes, lidocaine progressively shifted the peak frequency content from 84 +/- 18 mV2/Hz in the 10 to 20 Hz frequency band during the pre-lidocaine phase to 110 +/- 34 mV2/Hz in the 0 to 10 Hz frequency band immediately prior to conversion to normal sinus rhythm. When atropine was administered or electrical vagal stimulation was discontinued, the conversion of atrial fibrillation to normal sinus rhythm followed a similar electrophysiologic pattern. When isoproterenol was infused, it was difficult to induce atrial fibrillation; when the arrhythmia was initiated, it could not be sustained even with concomitant electrical vagal stimulation. Thus in this model of parasympathetically sustained atrial fibrillation, lidocaine was 100% effective in converting atrial fibrillation to normal sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330865 TI - Atrial and ventricular arrhythmias in asymptomatic active elderly subjects: correlation with left atrial size and left ventricular mass. AB - Elderly normal subjects have an increased prevalence of cardiac arrhythmias compared with young and middle-aged subjects. The objective of this study was to test the hypothesis that the incidence and complexity of atrial and ventricular arrhythmias may be related to either left atrial enlargement or to increased left ventricular mass, respectively. From 146 asymptomatic volunteers older than 60 years, 86 subjects were considered to be free of cardiovascular abnormalities and had adequate M-mode echocardiograms and 24-hour ambulatory electrocardiograms. The mean age was 72 +/- 7 years, with a range of 60 to 96 years. There were 37 men and 49 women. During 1415 +/- 73 minutes of ambulatory electrocardiography, the average heart rate was 72 +/- 8 beats/min in men and 76 +/- 6 beats/min in women (p less than 0.05). Atrial arrhythmias were present in 64 subjects (74%); the frequency and complexity of these arrhythmias correlated with left atrial size (p less than 0.01). Ventricular arrhythmias were present in 55 subjects (64%); the frequency and complexity of ventricular arrhythmias did not correlate with left ventricular mass index. These results suggest that left atrial dilatation, a normal development in healthy elderly subjects, plays a significant role in the pathophysiology of the increased incidence of atrial arrhythmias. Increased left ventricular mass, which also occurs normally in the aging heart, is not, on the other hand, associated with an increased frequency and/or complexity of ventricular arrhythmias. PMID- 2330866 TI - Safety and utility of transesophageal echocardiography in the critically ill patient. AB - We studied the safety and utility of transesophageal echocardiography in the evaluation of critically ill patients in the intensive care unit setting. Sixty two studies were performed in four different intensive care units on 61 patients with a mean age of 58 +/- 14 years (range 25 to 78 years). Indications for the study included suspected aortic pathologic conditions (18 patients), cardiac source of embolus (16 patients), postmyocardial infarction complications (6 patients), and suspected infective endocarditis (5 patients). Studies were performed at bedside with the use of small amounts of intravenous sedatives. The probe was passed successfully in 61 of 62 attempts. Diagnoses that were missed by surface echocardiography, including aortic dissection, left atrial thrombus, ruptured papillary muscle, and prosthetic valve vegetation were clearly identified by transesophageal echocardiography, which facilitated appropriate management in these cases. In cases in which no pathologic condition was identified, transesophageal echocardiography was useful in ruling out intracardiac shunt, in assessing left ventricular function, and in excluding significant valvular pathologic conditions. No serious complications were recorded, and the procedure was, in general, very well tolerated. PMID- 2330867 TI - Echocardiography in diagnostic assessment of peripheral arterial embolization. AB - In an attempt to identify a cardiac source of emboli, two-dimensional echocardiography was performed postoperatively in 42 consecutive patients with acute peripheral arterial embolism requiring urgent embolectomy. The patients were divided into four groups. Group 1 included 14 patients with chronic atrial fibrillation, among whom four cases of intracavitary thrombi were detected. Group 2 included 13 patients with acute or previous myocardial infarction, and left ventricular thrombi were detected in three. Group 3 included one patient with a prosthetic mechanical aortic valve and one with mitral valve prolapse; thrombi were not detected in either. Group 4 comprised 13 patients with no clinical evidence of a cardiac source of embolism; in one of them a large left ventricular thrombus was detected. Altogether eight intracavitary thrombi were detected (19%), and only in three (7.1%) were the results of echocardiographic examinations defined as entirely normal. A number of clinically undetected cardiac lesions, such as mitral annular calcification and aortic valve calcification, possibly associated with peripheral arterial embolism, were also detected by postoperative echocardiography. Because of the high percentage of intracavitary thrombi detected and the therapeutic implications thereof, especially if embolism recurred, it is concluded that two-dimensional echocardiographic examination should be recommended for patients with acute peripheral embolism. PMID- 2330868 TI - Relation of echocardiographic morphology of the mitral apparatus to mitral regurgitation in mitral valve prolapse: assessment by Doppler color flow imaging. AB - Few data exist regarding the relationship of valvular anatomy and coaptation to the presence of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP). Therefore this study was undertaken to assess the ability of two dimensional echocardiographic features of mitral valve morphology to predict the presence, direction, and magnitude of MR as assessed by color Doppler flow imaging. MR was present in 21 of 46 patients with MVP on two-dimensional echocardiography. Echocardiograms were specifically evaluated for leaflet apposition, leaflet morphology, and mitral anulus diameter. Color flow images were analyzed for presence of MR, direction of the regurgitant jet, and area encompassing the largest jet visible in any view. Abnormal mitral leaflet coaptation on two-dimensional echocardiography was strongly associated with the presence of MR (p = 0.003), being present in 15 of 21 patients with as compared with 5 of 25 patients without MR. Similarly, mitral leaflet thickness and MR were closely associated (p = 0.0035), with the latter being present in 9 of 30 patients with normal and 12 of 16 patients with excessive leaflet thickness. MR jet direction tended to be anterior to central with posterior leaflet prolapse and posterior or central with anterior leaflet prolapse (p = 0.02). Maximal jet area of MR tended to be larger in patients with compared with those without mitral annular dilatation (5.4 +/- 2.3 versus 2.1 +/- 1.9 cm2, p = 0.001), and in those with abnormal rather than normal leaflet thickness (4.5 +/- 2.7 versus 2.0 +/- 1.6 cm2, p = 0.009). Thus the presence, direction, and size of MR jets in MVP are related to structural abnormality of the mitral apparatus on echocardiography. PMID- 2330869 TI - Nuclear magnetic resonance imaging of the pulmonary arteries, subpulmonary region, and aorticopulmonary shunts: a comparative study with two-dimensional echocardiography and angiography. AB - Twelve patients more than 8 years of age with complex congenital heart disease were evaluated prospectively with nuclear magnetic resonance (NMR) imaging and with echocardiographic and angiographic imaging techniques. The subpulmonary region, main pulmonary artery, right and left pulmonary arteries, and aorticopulmonary shunts were clearly visualized by means of NMR imaging in all patients. Angiography defined the subpulmonary region and main pulmonary artery in all patients, the right and left pulmonary arteries along their length in 11 of 12 patients, and aorticopulmonary shunts in seven of eight patients. Except for the right pulmonary artery, echocardiography defined the remaining structures in less than or equal to 50% of patients. Measurement of the pulmonary artery diameters on NMR images correlated well with the angiographic measurements of both the left (r = 0.96) and right (r = 0.94) pulmonary arteries. These results suggest that NMR imaging may be the preferable noninvasive imaging technique for defining the anatomy of the subpulmonary region, main and left pulmonary arteries, and aorticopulmonary shunts in older patients with congenital cardiovascular disease and that it compares well with the angiographic standard. PMID- 2330870 TI - Prediction of outcome in late-stage cardiomyopathy. AB - One hundred thirty-three patients with dilated heart failure, 80 with coronary artery disease, and 53 with idiopathic dilated cardiomyopathy were followed for a mean of 29 months. Patients with ischemic heart disease had a worse prognosis than those classified as having idiopathic cardiomyopathy. Features from history, physical examination, and diagnostic tests done when patients were referred to our clinic were checked for univariate association with survival and were used in Cox model survival analysis to define risk groups. Neither the overall group nor either subgroup showed a relationship between ejection fraction and survival. The best variables for predicting long-term mortality included underlying coronary artery disease, basal systolic blood pressure of less than 120 mm Hg, presence of congestion on chest radiogram, and age over 64. Other variables did not improve risk prediction in the overall group. Among patients with ischemic heart disease, blood pressure, congestion, maximal heart rate on treadmill test, and the presence of left bundle branch block on the initial electrocardiogram all contributed. Only systolic blood pressure and the symptom score were related to survival in idiopathic cardiomyopathy. PMID- 2330871 TI - Pulmonary thallium uptake: correlation with systolic and diastolic left ventricular function at rest and during exercise. AB - Quantified pulmonary 201-thallium uptake, assessed as pulmonary/myocardial ratios (PM) and body surface area-corrected absolute pulmonary uptake (Pc), was determined from single photon emission computed tomography studies in 22 normal subjects and 46 consecutive patients with coronary artery disease (CAD). By means of equilibrium radionuclide angiography (ERNA), ejection fraction (EF), peak ejection rate (PER) in end-diastolic volume (EDV/sec) and peak filling rate (PFR) in EDV/sec and stroke volume (SV/sec) units, PFR/PER ratio, and time to peak filling rate (TPFR) in milliseconds were computed at rest and during exercise (n = 35). Left ventricular response to exercise was assessed as delta EF, relative delta EF, delta EDV, and delta ESV. In normal subjects the PM ratios showed significant inverse correlation with PER at rest and with EF, PER, and PFRedv during exercise. For the left ventricular response to exercise, delta ESV showed significant correlation with the PM ratios. The body surface area-corrected pulmonary uptake values showed no correlation with any of the variables. In patients with CAD the PM ratios and Pc uptake showed significant inverse correlation with EF, PER, PFRedv and to exercise EF, exercise PER, and exercise PFRedv. For the left ventricular response to exercise, delta EF showed significant inverse correlation with the PM ratios but not with the Pc uptake. Neither in normal subjects nor in patients with CAD did any of the independent diastolic variables show significant correlation with the PM ratios or Pc values. Thus pulmonary thallium uptake is correlated with systolic left ventricular function at rest and during exercise in normal subjects and in patients with CAD but not with diastolic function. In normal subjects delta ESV and in patients with CAD, delta EF showed correlation with pulmonary thallium uptake. PMID- 2330872 TI - Frequency and significance of chamber collapses during cardiac tamponade. PMID- 2330874 TI - Prognostic significance of daily physical activity after first acute myocardial infarction. PMID- 2330873 TI - Morphologic findings in saphenous veins used as coronary arterial bypass conduits for longer than 1 year: necropsy analysis of 53 patients, 123 saphenous veins, and 1865 five-millimeter segments of veins. AB - Certain clinical and necropsy findings are described in 53 patients who died from 13 to 185 months (mean 58) after a single aortocoronary bypass operation. Of the 53 patients, 32 (60%) died of a cardiac cause and of their 72 saphenous vein aortocoronary conduits, 36 (49%) were narrowed at some point more than 75% in cross-sectional area by atherosclerotic plaque; the remaining 21 patients (40%) died of a noncardiac cause and of their 50 saphenous vein conduits, 10 (20%) were narrowed at some point more than 75% in cross-sectional area by plaque. Thus the noncardiac mode of death in a large percentage of the patients suggests that the bypass operation prolonged life to a degree sufficient for another condition to develop. The 123 saphenous vein conduits were divided into 5 mm segments, and a histologic section was prepared from each. Of the 1104 five-millimeter segments in the 32 patients dying as a consequence of myocardial ischemia, 291 (26%) were narrowed more than 75% in cross-sectional area by plaque; in contrast, of the 761 five-millimeter segments of veins in the 21 patients with a noncardiac mode of death, 86 (11%) were narrowed more than 75% by plaque. Of the total 1865 five millimeter segments of vein, only 395 (21%) were narrowed 25% or less in cross sectional area by plaque. Thus, in patients dying late after coronary bypass the atherosclerotic process continues in all segments of the saphenous veins used as aortocoronary conduits. Therapy after the operation must be directed toward prevention of progression of the atherosclerosis in the "new" coronary "arteries." PMID- 2330875 TI - Circulatory collapse following coronary bypass surgery: multivessel and graft spasm reversed in the catheterization laboratory by intracoronary papaverine. PMID- 2330876 TI - Angina and threatened acute myocardial infarction after cardiac transplantation. PMID- 2330877 TI - Coronary dissection after aortocoronary bypass surgery associated with amyloidosis and atherosclerosis of the epicardial vessels. PMID- 2330878 TI - Urgent surgical removal of a rapidly growing left ventricular thrombus following acute myocardial infarction. PMID- 2330879 TI - Successful percutaneous removal of retained probe balloon wire during coronary angioplasty. PMID- 2330880 TI - Acute mitral regurgitation with cardiogenic shock in a patient with hypertrophic cardiomyopathy: a critical management dilemma. PMID- 2330881 TI - Right ventricular pseudoaneurysm following repair of tetralogy of Fallot. PMID- 2330882 TI - Transesophageal echocardiographic recognition of mitral valve abnormalities associated with aortic valve endocarditis. PMID- 2330883 TI - Vegetations on endocardial surfaces struck by regurgitant jets: diagnosis by transesophageal echocardiography. PMID- 2330885 TI - Right heart metastatic endocardial implants: echocardiographic and pathologic correlation. PMID- 2330884 TI - Cardiac lipoma in the interventricular septum: evaluation by computed tomography and magnetic resonance imaging. PMID- 2330886 TI - Hemodynamic findings in extrapericardial atrial tamponade. PMID- 2330887 TI - Exercise-induced T wave normalization is not specific for myocardial ischemia detected by perfusion scintigraphy. PMID- 2330888 TI - Reduction in Q wave myocardial infarctions with gemfibrozil in the Helsinki Heart Study. AB - The Helsinki Heart Study demonstrated a 34% (p less than 0.02) reduction in the incidence of cardiac end points (myocardial infarction and cardiac death) with the use of gemfibrozil compared with the use of a placebo in dyslipidemic middle aged men. The major effect was confined to nonfatal myocardial infarctions. In this study we analyzed the effect of gemfibrozil therapy on the incidences of Q wave and non-Q wave infarctions, since the long-term prognoses of these two types of myocardial infarction may be different. The analyses indicated a 45% reduction (P less than 0.02, log-rank test) in the cumulative incidence of Q wave infarctions in the gemfibrozil group without a statistically significant effect on either the rate of non-Q wave infarctions or of coronary deaths. The reduction in the incidence of Q wave infarctions became evident during the second half of the 5-year study period. PMID- 2330889 TI - Impact of atrial fibrillation on the in-hospital and long-term survival of patients with acute myocardial infarction: a community-wide perspective. AB - As part of an ongoing community-wide study examining changes over time in the incidence and survival rates of 4108 patients hospitalized with validated acute myocardial infarction (MI) in 16 hospitals in the Worcester, Massachusetts, metropolitan area during calendar years 1975, 1978, 1981, 1984, and 1986, we examined changes over time in the proportion of patients with acute MI developing atrial fibrillation (AF) and the impact of AF on in-hospital and long-term survival for up to a 10-year follow-up period. The overall percentage of patients with AF complicating acute MI was 16.0%; this proportion increased over time from 13.3% in 1975 to 14.8% in 1978, 14.9% in 1981, 20.3% in 1984, and to 17.7% in 1986. Patients with AF experienced consistently higher in-hospital case fatality rates than MI patients without AF overall (27.6% versus 16.6%), as well as during each of the 5 years under study. The independent effect of AF on in-hospital survival was not upheld, however, when a variety of potentially confounding prognostic factors were controlled for in a multivariate analysis resulting in an adjusted odds ratio (OR) of 1.18 (95% confidence interval 0.90, 1.52). Among discharged hospital patients, while the crude long-term survival rate for patients with AF was poorer than that of patients without AF for the combined as well as for individual study periods, similar to the in-hospital findings the independent effect of AF on long-term prognosis was not upheld after use of a multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330890 TI - Prognostic significance of sustained monomorphic ventricular tachycardia induced by programmed ventricular stimulation using up to triple extrastimuli in survivors of acute myocardial infarction. AB - The prognostic significance of sustained monomorphic ventricular tachycardia (VT) induced by programmed ventricular stimulation using up to 3 extrastimuli was evaluated in 133 consecutive survivors of acute myocardial infarction (AMI) at a mean interval of 1.8 +/- 1.1 months after onset. This was compared with hemodynamic and angiographic abnormalities shown by cardiac catheterization and ventricular ectopic activity detected by Holter monitoring. Sustained monomorphic VT was induced in 25 (19%) patients, sustained polymorphic VT in 11 (8%) patients, nonsustained monomorphic VT (greater than or equal to 10 beats) in 12 patients (9%) and nonsustained polymorphic VT in 9 patients (7%). Multivariate logistic regression analysis of clinical, angiographic, hemodynamic and electrocardiographic variables showed that the presence of a left ventricular aneurysm (p = 0.005) and Lown grade 4B ventricular ectopic activity (p less than 0.001) were independent predictors of inducibility of sustained monomorphic VT. During a mean follow-up of 21 +/- 13 months, there were 8 (6%) sudden cardiac deaths and 3 (2.3%) spontaneous occurrences of life-threatening sustained VT. The 2-year probability of freedom from sudden cardiac death or sustained ventricular tachyarrhythmias was 53 +/- 13% for patients with inducible sustained monomorphic VT, 70 +/- 10% for those with a left ventricular ejection fraction less than 40% and 58 +/- 13% for those with Lown grade 4B ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330891 TI - Frequency, characteristics and significance of supraventricular tachyarrhythmias detected by 24-hour electrocardiographic recording in the late hospital phase of acute myocardial infarction. AB - The incidence, characteristics and clinical significance of supraventricular tachyarrhythmias occurring in the late hospital phase of acute myocardial infarction (AMI) were assessed in 209 consecutive patients. Arrhythmias were quantified by 24-hour electrocardiographic recording 16 +/- 3 days after AMI, and were classified according to the degree of complexity in 5 classes. Class 0 = less than 5 premature beats/hr; class 1 = between 5 and 100/hr; class 2 = greater than 100/hr or repetitive premature beats; class 3 = atrial-junctional tachycardia; class 4 = atrial flutter-fibrillation. Supraventricular tachyarrhythmias classes 1 to 2 always occurred in the absence of symptoms in 86 patients (41%); supraventricular tachyarrhythmias classes 3 to 4 (paroxysmal, self-limiting, brief) occurred in 27 patients (13%), symptomatically in 6. The presence of supraventricular tachyarrhythmias classes 2 to 3 was related to age over 55 years and complex ventricular tachyarrhythmias (greater than 20 premature beats/hr, ventricular tachycardia) (both p less than 0.05). Increasing complexity of supraventricular tachyarrhythmias was significantly associated with presence and entity of cardiac enlargement and left ventricular dysfunction (both p less than 0.01). Patients with class 4 showed the most severe cardiac deterioration. During the 2 years after AMI, patients with classes 2, 3 and 4 had a higher incidence of acute pulmonary edema, New York Heart Association functional classes III to IV for congestive heart failure (both p less than 0.005) and a greater need of digitalis and diuretics (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330892 TI - Comparison of contrast angiography and two-dimensional echocardiography for the evaluation of left ventricular regional wall motion abnormalities after acute myocardial infarction. AB - Regional left ventricular wall motion abnormalities were assessed using 2 dimensional echocardiography and contrast ventriculography within 12 hours of the onset of chest pain in 20 patients with acute myocardial infarction (AMI); 10 patients had anterior infarctions and 10 had inferior. End-diastolic and end systolic sinus beats from right anterior oblique contrast ventriculograms were analyzed using the center-line chord technique with both a standard overlap method of chord assignment and a nonoverlap method. Echocardiograms were obtained in parasternal long- and short-axis and apical 2- and 4-chamber views and analyzed using a 16-segment scoring system to derive anterior and infero posterolateral wall motion indexes using both overlap (10 segments for anterior, 8 inferior) as well as nonoverlap (9 segments anterior, 7 inferior) methods of segment assignment. There was a significant inverse correlation between the standard (nonoverlap) echocardiographic analysis and the standard (overlap) angiographic analysis for infarct regions (y = -0.43 X +1.11, r = -0.59, p less than 0.05). Fifteen of 18 patients with angiographic infarct regional score less than or equal to -1 standard deviation/chord had an echocardiographic index greater than or equal to 1.5, while 15 of 16 patients with echocardiographic regional infarct index greater than or equal to 1.5 had an angiographic score less than or equal to -1 standard deviation/chord. Correlation between the 2 methods for noninfarct territories was poor (r = -0.34) because the angiographic method assesses hyperkinesis while the echocardiographic method does not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330893 TI - Diagnostic value of ambulatory Holter monitoring for the detection of coronary artery disease in patients with variable threshold angina pectoris. AB - Patients with chronic stable angina pectoris may present with either fixed or variable threshold symptoms. To evaluate the diagnostic value of ambulatory Holter monitoring for the detection of coronary artery disease (CAD) in patients with variable threshold angina, 216 consecutive candidates for coronary angiography were investigated prospectively. For comparison, a group of 55 consecutive patients with fixed threshold angina was studied under the same conditions. Patients with prior myocardial infarction or angiographically documented CAD were excluded. Within 4 months of Holter monitoring, the advised coronary angiography was performed in 77% of the patients with variable threshold angina and in 89% of the patients with fixed threshold angina (p less than 0.05). The prevalence of CAD was markedly lower in patients with variable threshold angina compared to patients with fixed threshold angina (54 vs 90%, p less than 0.001). CAD patients of both subgroups, however, did not differ significantly with respect to the number of obstructed vessels, the Gensini coronary score, the number with impaired left ventricular function (ejection fraction less than 50%) or the duration of ischemic episodes during Holter monitoring. Diagnostic accuracy of Holter monitoring did not differ between variable and fixed threshold angina groups (67 vs 78%). In 91% of the patients results obtained by Holter monitoring could be compared to the results of a bicycle stress test. In patients with fixed threshold angina the diagnostic accuracy was similar for both tests (80 vs 80%). In patients with variable threshold angina, the diagnostic accuracy of Holter monitoring exceeded that of the exercise stress test (68 vs 55%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330894 TI - Signal-averaged electrocardiographic late potentials in resuscitated survivors of out-of-hospital ventricular fibrillation. AB - The results of signal-averaged electrocardiography and programmed electrical stimulation were evaluated in 25 patients with recurrent sustained ventricular tachycardia (VT) and 46 patients with a history of out-of-hospital ventricular fibrillation (VF) to characterize the electrophysiologic substrate responsible for these different clinical arrhythmia presentations. Patients with VT had a higher incidence of late potentials (VT 83%, VF 50%, p = 0.005). Significant differences between these groups were also noted in response to programmed electrical stimulation. A sustained ventricular arrhythmia was induced in 24 of 25 (96%) patients with a history of VT but in only 27 of 46 (59%) of VF patients (p = 0.005). In addition, VF was induced in 11 (24%) patients in the VF group but in none of the patients in the VT group (p = 0.005). When the 2 groups were compared on the basis of select clinical characteristics, no significant difference in age, sex, presence of coronary artery disease or ejection fraction was noted. The frequency of prior myocardial infarction was significantly higher in the VT group (VT 20 of 25, 80%; VF 24 of 46, 52%; p = 0.03). Finally, no significant relation between the presence of late potentials and induced arrhythmias was noted in either group. The inability of signal-averaged electrocardiography to predict inducibility in VF patients may represent a significant limitation of this technique in identifying patients at risk for sudden cardiac death. PMID- 2330895 TI - Usefulness of right ventricular pulse pressure as a potential sensor for hemodynamically unstable ventricular tachycardia. AB - The automatic implantable cardioverter defibrillator has had a major impact on the management of patients with ventricular tachyarrhythmias. Future devices will offer tiered therapy for ventricular arrhythmias, based on a sensor capable of discriminating hemodynamically stable from unstable ventricular tachycardia (VT). We studied 27 patients with sustained VT/ventricular fibrillation during 70 episodes of sustained ventricular arrhythmias (greater than 30 seconds or requiring cardioversion). In this study, phasic arterial pressure (mm Hg), VT cycle length (ms) and right ventricular (RV) pulse pressure (mm Hg) were measured before, during the first 30 beats and after each episode of VT. During the first 10 beats of 23 episodes of unstable VT, the mean (+/- standard error of the mean) decrease in RV pulse pressure from baseline was 22 +/- 1.8 mm Hg; it was 13.8 +/- 2.4 mm Hg during the first 10 beats of 47 episodes of stable VT, (p = 0.01, stable vs unstable). For the next 20 beats of VT, RV pulse pressure decreased from baseline by 22 +/- 2.5 mm Hg during unstable and by 12.0 +/- 2.5 mm Hg during stable VT (p = 0.0001, stable vs unstable). The percent decrease of RV pulse pressure correlated well with the percent decrease in mean arterial pressure and percent decrease in systolic arterial pressure (r = 0.70; r = 0.69, respectively; p less than 0.001) during VT, but poorly with the VT cycle length (r = 0.27, p less than 0.05). The percent decrease in RV pulse pressure is a useful hemodynamic sensor for discriminating between stable and unstable VT. PMID- 2330897 TI - Right ventricular diastolic function in systemic hypertension. AB - Right (RV) and left ventricular (LV) diastolic function was evaluated in 50 patients with mild, uncomplicated essential hypertension using pulsed-wave Doppler echocardiography. Patients with pulmonary, valvular or coronary artery disease were excluded and antihypertensive drugs were discontinued for the 2 weeks preceding the study. Ten normotensive patients without heart disease acted as control subjects. In the hypertensive patients, RV peak velocity of atrial filling was higher (42 +/- 10 vs 31 +/- 7 cm/s, p less than 0.01) and deceleration half-time was prolonged (96 +/- 20 vs 83 +/- 10 ms, difference not significant); ratio of early/atrial filling velocity (1.1 +/- 0.3 vs 1.7 +/- 0.4, p less than 0.001) and peak filling rate corrected to stroke volume (3.6 +/- 0.7 vs 5.3 +/- 0.9 SV/s, p less than 0.001) were lower. LV filling parameters showed similar changes. RV filling parameters did not correlate with age, LV mass or septal thickness but correlated weakly with LV radius/thickness ratio. There was good correlation between RV and the following corresponding LV filling parameters: peak filling rate, r = 0.68, p less than 0.001; ratio of early/atrial filling, r = 0.88, p less than 0.0001; and deceleration half-time, r = 0.62, p less than 0.001. Data indicate that RV diastolic function is abnormal in essential hypertension and these abnormalities are closely related to those of LV diastolic function. PMID- 2330896 TI - Risk for systemic embolization of atrial fibrillation without mitral stenosis. AB - The risk for systemic embolization was studied in 272 patients without mitral stenosis or prosthetic valves who were referred to the echocardiography laboratory with atrial fibrillation (AF). During a mean follow-up period of 33 months (range less than 1 to 83), 27 (10%) patients had a systemic embolic event, which was cerebral in 23 patients (85%) and peripheral in 4 (15%). In the analysis of individual variables, the risk of embolization was increased by female sex, underlying heart disease and left atrial size greater than or equal to 4.0 cm, but not by age, hypertension or type of AF (paroxysmal vs chronic). In multivariable analysis, left atrial size greater than or equal to 4.0 cm was the single strongest predictor of increased risk for embolization (p less than 0.001), but female sex (p = 0.014) and underlying heart disease (p = 0.027) also contributed. When each of these 3 factors was assigned 1 point in a risk score, embolic events were found to occur in none (0%) of 24 patients with a risk score of 0, in 2 (3%) of 83 patients with a risk score of 1, in 13 (11%) of 118 patients with a risk score of 2 and in 12 (26%) of 47 patients with a risk score of 3. The score allows patients with AF and without mitral stenosis to be stratified into high-, medium- and low-risk groups for systemic embolization. Such information could be useful in decision making for anticoagulation in patients with AF. PMID- 2330898 TI - Effect of dobutamine on skeletal muscle metabolism in patients with congestive heart failure. AB - Dobutamine is known to increase leg blood flow during exercise in patients with heart failure. However, it is uncertain whether the increased flow is delivered to working skeletal muscle. In 7 patients with heart failure, the effects of dobutamine were examined on calf phosphorus-31 magnetic resonance spectroscopy (MRS) spectra and femoral vein blood flow during rest and upright plantar flexion. During upright plantar flexion every 3 seconds, dobutamine increased femoral venous blood flow (control 1.7 +/- 0.1; dobutamine 2.1 +/- 1.0 liters/min; p less than 0.05) and increased femoral venous O2 saturation (control 24 +/- 5%; dobutamine 31 +/- 2%; p less than 0.05), indicating improved total leg blood flow. However, dobutamine did not change the slope of the relation between systemic VO2 and the calf inorganic phosphate to phosphocreatine relation (control 0.0054 +/- 0.0039; dobutamine 0.0056 +/- 0.0032; difference not significant) and did not change muscle pH, suggesting no improvement in blood flow to active skeletal muscle. These findings suggest that dobutamine does not improve oxygen delivery to working skeletal muscle in patients with heart failure, despite its ability to increase cardiac output and limb blood flow. PMID- 2330899 TI - Assessment of peak oxygen consumption, lactate and ventilatory thresholds and correlation with resting and exercise hemodynamic data in chronic congestive heart failure. AB - To determine the clinical value of respiratory gas analysis during exercise, oxygen consumption (VO2) at peak exercise and at lactate and ventilatory threshold was assessed in 34 patients with chronic heart failure who underwent maximal exercise testing with expiratory gas monitoring and serial determinations of mixed venous lactate and hemodynamics by Swan-Ganz catheterization. A lactate threshold, defined as the point of abrupt increment of blood lactate, could be identified in every patient; the ventilatory threshold, detected on the basis of the respiratory changes, was found in 26 patients (77%). Lactate and ventilatory thresholds were significantly related to each other (r = 0.94; p less than 0.001) and to peak VO2 (r = 0.89; p less than 0.001 in both). Among the resting hemodynamic measurements, peak VO2 was significantly related only to total pulmonary resistances (r = -0.35). Among the parameters at maximal exercise, it was positively related to cardiac index, stroke work, stroke volume index and mean arterial pressure (r = 0.89, 0.74, 0.74 and 0.56, respectively) and inversely related to systemic vascular and total pulmonary resistances (r = -0.74 and -0.63). Using multivariate stepwise regression analysis only maximal cardiac index and, to a lesser degree, total pulmonary resistance were related to peak VO2. Similar correlations were found between the hemodynamics and the lactate and ventilatory threshold. Thus, peak VO2, lactate and ventilatory thresholds can be detected in most patients with chronic heart failure. These parameters are highly correlated to each other and bear similar relations to the hemodynamic response to exercise. The cardiac index is the main central hemodynamic determinant of exercise capacity. PMID- 2330900 TI - Decreased coronary vasodilatory capacity in hypertrophic cardiomyopathy determined by split-dose thallium-dipyridamole myocardial scintigraphy. AB - Split-dose thallium-dipyridamole myocardial scintigraphy was performed in patients with nonobstructive hypertrophic cardiomyopathy (HC) who had angiographically normal coronary arteries. The dipyridamole-induced increases in thallium-201 uptake, calculated to evaluate coronary vasodilatory capacity, were significantly lower in 30 patients with HC than in 13 control subjects (177 +/- 58 vs 281 +/- 46%) and the reductions were observed in both the septal and lateral segments. The reductions of the septal segment in HC patients were significantly greater than those in 10 hypertensive patients with comparable degrees of septal hypertrophy. Of patients with HC, 16 had increases in thallium uptake well below the normal range. Compared with those having normal increases, these patients had significantly lower exercise duration (11 vs 15 minutes), with 33% having ST depression develop at a workload less than or equal to 80 watts. These data indicate that approximately one-half of patients with HC have impaired coronary vasodilatory capacity that could be an important pathophysiologic abnormality of HC resulting in the development of myocardial ischemia and the impairment of cardiac performance during exercise. PMID- 2330901 TI - Echocardiographic assessment of the left ventricle of endurance athletes just before and after exercise. AB - Fourteen normal subjects and 10 marathon runners were studied using postexercise echocardiography to assess left ventricular (LV) wall thickness, afterload and systolic performance. Cuff systolic blood pressures and M-mode echocardiographic recordings were obtained in the supine position before and within 2 minutes of termination of maximal treadmill exercise. Both groups had increased LV dimensional shortening (% fractional shortening) and stroke volume after exercise, although runners had larger increases compared to untrained normal subjects (p less than 0.05). Preload, as estimated by LV end-diastolic dimension, was greater in runners compared to normal subjects at rest (52 vs 48 mm, p less than 0.05). However, preload did not change after exercise in either group. Afterload, estimated by LV end-systolic wall stress, decreased after exercise in both groups; however, runners had lower afterload at rest and immediately after exercise compared to normal subjects (p less than 0.05). The runners' greater LV end-systolic wall thickness appears to account for their lower afterload. Data indicate that marathon runners have lower afterload at rest and greater decrease in afterload after maximal exercise, compared to untrained normal subjects. PMID- 2330902 TI - Cardiac involvement in systemic lupus erythematosus detected by echocardiography. AB - Cardiac involvement in patients with systemic lupus erythematosus (SLE) was assessed by full echocardiography and continuous wave Doppler in 50 consecutive patients and 50 age- and sex-matched control subjects in a prospective, blinded study. The left ventricular ejection fraction was decreased in patients compared to control subjects (61 +/- 9 vs 68 +/- 7%, p less than 0.001), whereas interventricular septum (12 +/- 3 vs 9 +/- 1 mm, p less than 0.001), and posterior wall dimension (9 +/- 2 vs 8 +/- 1 mm, p less than 0.001), left ventricular mass (186 +/- 54 vs 130 +/- 32 g, p less than 0.001) and mitral valve Doppler A:E ratio (0.8 +/- 0.2 vs 0.7 +/- 0.1, p less than 0.01) were increased. Pericardial effusion was detected in 27 patients and 5 control subjects, and valvular regurgitation was more frequent in the patients (aortic 2 vs 0; mitral 23 vs 5, p less than 0.001; tricuspid 34 vs 22, p less than 0.01 and pulmonary 28 vs 17, p less than 0.05). Mitral or aortic regurgitation was more common in patients with active SLE (60 vs 40%, difference not significant) but was not related to the duration of SLE (r = 0.02), duration of prednisone therapy (r = 0.13) or current dosage of prednisone (r = 0.01). This study demonstrates that pericardial effusion, valvular regurgitation and myocardial abnormalities are frequently present in patients with SLE. PMID- 2330903 TI - Prevalence and clinical implications of atrial spontaneous contrast in patients undergoing transesophageal echocardiography. AB - The prevalence of atrial spontaneous contrast was evaluated in 150 consecutive patients undergoing transesophageal echocardiography. Spontaneous contrast was observed in 29 patients (19%). It was seen in the left atrium in 24 patients, in the right atrium in 4 patients and in both atria in 1 patient. Spontaneous atrial contrast was not seen in the absence of an associated cardiac abnormality. Univariate analysis showed a significant relation between the presence of spontaneous contrast and significant mitral regurgitation (p less than 0.05), the presence of mitral valve prostheses (p less than 0.001), atrial fibrillation (p less than 0.0001) and left atrial size (p less than 0.001). Multivariate analysis showed that the presence of atrial fibrillation, prosthetic mitral valve and atrial size were independent factors for the presence of spontaneous contrast. However, of the 29 patients with spontaneous contrast, 13 (45%) were in sinus rhythm and in only 4 (16%) was the left atrial size greater than 60 mm. Left atrial thrombus was detected in 9 of the 150 patients. Although spontaneous contrast was noted in 5 (55%) patients with left atrial thrombus and in only 20 (14%) patients without left atrial thrombus (p less than 0.001), none of the 3 patients who had right atrial thrombus had spontaneous contrast in that chamber. Overall, 7 (58%) of the 12 patients with right or left atrial thrombi had no evidence of spontaneous contrast. Multivariate analysis showed that atrial fibrillation was the only independent clinical predictor of left atrial thrombus. Thus, spontaneous echocardiographic contrast is a common phenomenon observed in approximately 20% of the patients undergoing transesophageal echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330904 TI - Editorial board meeting of the American Journal of Cardiology--March 1990. PMID- 2330905 TI - A symposium: Indapamide and antihypertensive strategy. April 28, 1989, Barcelona, Spain. Proceedings. PMID- 2330906 TI - Effects of indapamide on the mechanical properties of the arterial wall in deoxycorticosterone acetate-salt hypertensive rats. AB - An experimental model of "in situ" isolated carotid artery has been used to evaluate the static mechanical properties of the arterial wall in 12-week-old Wistar and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The rats were made hypertensive by left kidney removal, DOCA (50 mg) tablet implantation for 2 weeks, and saline diet (NaCl 9% solution as beverage). Normotensive control rats (n = 24) and DOCA-salt hypertensive rats (n = 24) received indapamide, 10 mg/kg, or placebo by gavage 12 hours and 1 hour before measurements were obtained. The rats were anesthetized (pentobarbital 50 mg/kg), intubated and ventilated, and a midsternal thoracotomy was performed. A first catheter was introduced into the ascending aorta through the right carotid artery. A perivascular ultrasonic flow probe was placed around the ascending aorta and allowing simultaneous recording of the phasic ascending aortic pressure and flow. Systolic and diastolic pressure, cardiac output and heart rate were directly measured. Peripheral resistance and systemic arterial compliance were calculated from hemodynamic records. After hemodynamic measurements, a segment of the left carotid artery was then isolated in vivo and its volume-pressure relationship was recorded before and 30 minutes after total abolition of the vascular muscle tone by local incubation with a potassium cyanide solution (KCN) (100 mg/liter) for pressures ranging from 50 to 175 mm Hg. The carotid compliance (CC) (microliter/mm Hg) was calculated, for every pressure step, as the slope of the volume-pressure curves. Indapamide significantly reduced the arterial pressure in hypertensive rats, and this was related to a marked decrease in total peripheral resistance. Heart rate was not modified by indapamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330907 TI - Efficacy of antihypertensive treatment with indapamide in patients with noninsulin-dependent diabetes and persistent microalbuminuria. AB - In patients with insulin-dependent diabetes, antihypertensive treatment has a beneficial effect on the rate of progression toward uremia of overt diabetic nephropathy (albumin excretion rate [AER] greater than 300 mg/24 hour). The influence of hypertension on the progression of "incipient" nephropathy (AER ranging between 30 and 300 mg/24 hours) is not well defined, particularly in patients with noninsulin-dependent diabetes. In this study, 21 patients with noninsulin-dependent diabetes and hypertension (11 with normoalbuminuria and 10 with microalbuminuria), who were comparable for age, duration of diabetes and hypertension, were treated with indapamide, 2.5 mg once daily, and followed up for 24 months. Blood pressure, glomerular filtration rate (GFR), albumin excretion rate and subclass 4 of urinary immunoglobulin G (IgG4) were indicated. In normoalbuminuric patients, blood pressure was significantly reduced, whereas AER, IgG4 and GFR did not show any variation throughout the study. In microalbuminuric patients, blood pressure, AER and IgG4 were significantly reduced, and GFR remained unchanged. In patients with noninsulin-dependent diabetes, antihypertensive treatment, which is begun during incipient diabetic nephropathy, may have a beneficial effect on the progression of the disease, although a long-term follow-up study is needed to confirm this. PMID- 2330908 TI - Twenty-four-hour blood pressure monitoring and effects of indapamide. AB - Twenty-four-hour blood pressure (BP) monitoring with a noninvasive device (Kontron) has been used to assess the effect of a single dose of indapamide in a group of patients with essential hypertension. Originally 23 patients were selected. Three patients withdrew from the study because of refusal to go through the second 24-hour recording. Eight of the remaining patients had to be excluded for technical reasons, which left 12 patients available for analysis. All patients received a single dose of indapamide, 2.5 mg/day. Before treatment began, a 24-hour BP control was performed, and a second one a month later (37 +/- 8 days). The age of the patients was 46 +/- 10 years. Diurnal BP (8 am to 10 pm) and heart rate were, respectively, 148 +/- 15/101 +/- 6 mmHg and 79 +/- 9 beats/min; night BP (10 pm to 8 am) was 131 +/- 15/88 +/- 7 mmHg and heart rate 71 +/- 10 beats/min. After therapy, diurnal BP was 131 +/- 15/92 +/- 7 mmHg (-15 +/- 7/-8 +/- 4: p less than 0.0001/p less than 0.0001); heart rate 82 +/- 8 beats/min (difference not significant); night BP was 115 +/- 13/80 +/- 8 mmHg ( 16 +/- 11/-8 +/- 7: p less than 0.0001/p less than 0.0001) and heart rate 70 +/- 9 beats/min (difference not significant). Twenty-four-hour systolic work values were 106 +/- 15 at the beginning of the trial and 96 +/- 14 (-9.7 +/- 14; p less than 0.05) after 1 month of indapamide treatment. Variability did not change with treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330909 TI - DTP vaccine litigation, 1988. PMID- 2330910 TI - Origins of cerebral palsy. PMID- 2330911 TI - Perinatal asphyxia and other common causes of perinatal depression. PMID- 2330912 TI - Therapy--physical or otherwise--in cerebral palsy. PMID- 2330913 TI - Maternal abuse of cocaine and heroin. PMID- 2330914 TI - Capillary vs venous bilirubin values. PMID- 2330915 TI - Use of angiotensin converting enzyme inhibitors for the treatment of focal segmental glomerulosclerosis. PMID- 2330916 TI - International adoptees and hepatitis B virus infection. PMID- 2330917 TI - Lead poisoning presenting as intestinal ileus in a child. PMID- 2330918 TI - Antibiotic-associated pseudomembranous colitis. PMID- 2330919 TI - The unkindest cut. PMID- 2330920 TI - Trends in medical visits and surgery for otitis media among children. AB - We conducted a population-based descriptive study of medical visits and surgical interventions for otitis media among 3- and 7-year-old children from the Montreal, Canada, area over the period 1981 to 1983. The number of children seen annually for otitis media increased over that time. An increase in the event rate of otitis was observed; there was also an increase in the rate of myringotomy with ventilatory tube insertion. The rate of surgery reached a level, among 3 year-old children in particular (25.0 per 1000 cases of otitis among boys, 23.9 per 1000 cases of otitis among girls), that some authors have termed "epidemic." Comparison of the trends in the rates of surgical interventions and the rates of medical consultations for otitis suggest that most of this so-called surgical epidemic for middle ear effusion is related to a higher frequency of the underlying condition and not to more aggressive patterns of therapy during the years studied. PMID- 2330921 TI - Limiting treatment for extremely premature, low-birth-weight infants (500 to 750 g). AB - Despite impressive recent advances in neonatology, outcomes for extremely premature, very-low-birth-weight infants (500 to 750 g) remain uneven. In a situation of inherent uncertainty, treating patients vigorously could do violence to the moral principles of nonmaleficence and (distributive) justice. Equally, failing to treat patients vigorously because of concerns about nonmaleficence and (distributive) justice could violate the principle of patient-centered beneficence. Compounding this dilemma is the legacy of the "Baby Doe Regulations." International perspectives on this particular quandary are provided. We assert that at Stanford (Calif) University the "individualized prognostic strategy" rather than the "wait until certainty" approach prevails. Four concluding questions are posed: Why is prevention not encouraged more than after-the-fact heroic intervention? Is it possible to develop a more rational view of stopping aggressive therapy once having started? Can we ignore the finitude of our medical resources? Is there a need to redefine the nature of autonomy? PMID- 2330922 TI - Energy intake, growth, and development in ventilated very-low-birth-weight infants with and without bronchopulmonary dysplasia. AB - Seventy-one ventilated very-low-birth-weight infants (birth weight, 500 to 1250 g) with (n = 30) and without (n = 41) bronchopulmonary dysplasia were studied to compare their growth achievements and to determine the association between neurodevelopmental outcome, growth, and nutrition. Growth delay was observed in both groups. No association was found between head circumference and percent weight loss, age to full gavage feeds, age to regain birth weight and energy intake at 2 and 4 weeks of life. Fifty percent of infants with bronchopulmonary dysplasia and 37% of the control group had minor and major handicap. Mean duration of assisted ventilation was significantly longer in handicapped infants (21.5 vs 12.5 days; F = 6.49; df = 1,53). No association was found between abnormal neurodevelopmental outcome and weight, length, and head circumference at 12 and 21 months after term. Although mean energy intake per kilogram per day at 2 weeks of life was significantly lower in handicapped infants (344.82 vs 412.86 kJ; F = 7.6; df = 1,53), age to regain birth weight, age to full feeds, percent weight loss, and energy intake at 4, 6, and 8 weeks of life did not differ significantly between normal and handicapped infants. Aggressive nutritional support to promote growth in ventilated very-low-birth-weight infants may not influence the neurodevelopmental outcome. PMID- 2330923 TI - Pulmonary syndrome in patients with thalassemia major receiving intravenous deferoxamine infusions. AB - Eight patients with transfusion-dependent thalassemia major were given continuous intravenous infusions of the chelator, deferoxamine mesylate, to reduce iron overload. Within 5 to 9 days of starting the infusions, four patients developed a pulmonary syndrome of moderate to life-threatening severity characterized by tachypnea, hypoxemia, and a diffuse interstitial pattern on chest roentgenogram. Pulmonary function studies showed restrictive dysfunction. Lung biopsy showed diffuse abnormalities with alveolar damage, interstitial fibrosis, and inflammation. The inflammatory infiltrate comprised lymphocytes, eosinophils, and mast cells. Exposure of the biopsy specimen to fluorescein-conjugated anti-IgE antibody showed fixation of IgE to the mast cell surface, suggesting a hypersensitivity reaction. Detailed studies failed to identify an infectious agent. The temporal relationship between drug administration and lung disease, and the clinical similarities in the four affected patients, strongly suggested a cause and effect relationship. We recommend that therapy with continuous intravenous infusions of deferoxamine be monitored carefully with respect to pulmonary status. PMID- 2330924 TI - Use of the Saxon test as a measure of saliva production in a reference population of schoolchildren. AB - The Saxon test, a simple, reproducible, and low-cost technique to test for xerostomia in adults was applied to 347 schoolchildren who were free from any known disease. The values in children differed significantly from the values in adults and increased slightly with age. The test can easily be performed on samples kept for 8 days at 4 degrees C or at room temperature. PMID- 2330925 TI - Radiological case of the month. Pulmonary arteriovenous fistula associated with Rendu-Osler-Weber syndrome. PMID- 2330926 TI - Picture of the month. Acrodysostosis. PMID- 2330927 TI - Health maintenance organizations vs indemnity insurance for children with chronic illness. Trading gaps in coverage. AB - There has been increasing discussion about the potential of health maintenance organizations to provide improved access to and coordination of care for children with complex conditions. This study compares benefits for a sample of health maintenance organizations and traditional indemnity insurers in Connecticut. We conclude that in Connecticut neither health maintenance organizations nor traditional indemnity insurers currently offer comprehensive systems of care to these children. Health maintenance organizations offer preventive care and are easier systems to access. However, for children with chronic conditions, health maintenance organizations have some problematic restrictions, including a lag between start of employment and activation of health care benefits. Both health maintenance organizations and traditional indemnity insurers tend to have restrictions for specific services needed by children with chronic illnesses, such as medical equipment and mental health services. Case managers in both systems tend to control expenditures rather than to coordinate care. Representatives of both systems predict additional restrictions in the future. Our data suggest the need for more extensive evaluation of the generalizability of these findings. PMID- 2330928 TI - Metalloporphyrin-enhanced photodegradation of bilirubin in vitro. AB - Solutions of bilirubin containing human serum albumin were exposed in vitro in the presence of 10 mumols/L of tin and zinc metalloporphyrins at 37 degrees C for 30 minutes to light sources used clinically for phototherapy of neonates. Bilirubin in the model solutions was photodegraded to approximately 60% of dark control in cool white light (17 microW/cm2 per nanometer). The presence of zinc protoporphyrin and zinc mesoporphyrin further reduced the bilirubin concentration slightly, but the tin analogues caused a significant enhancement of degradation to 35% and 25% of dark control, respectively. The results provide evidence that the zinc and tin metalloporphyrins are photosensitizers capable of enhancing the native photodegradation of bilirubin in biologic matrices, but that the tin compounds are more potent. The metalloporphyrin time course, dose-response curve, oxygen effects, and efficacy of phototherapy light sources were also studied. PMID- 2330929 TI - Live attenuated and inactivated influenza vaccine in school-age children. AB - In 1985, we enrolled 189 school-age children by family in a double-blind study to determine protection against influenza by a single dose of cold-recombinant bivalent A vaccine or commercial trivalent inactivated vaccine compared with placebo. All children in school or day care, 3 to 18 years of age, in an enrolled family received the same preparation. Following vaccination, 60% and 21% of cold recombinant bivalent A vaccine recipients and 73% and 83% of trivalent inactivated vaccine recipients demonstrated fourfold or greater response in hemagglutination-inhibition antibody titer to A/H1N1 and A/H3N2, respectively. Sixty-seven percent of all trivalent inactivated vaccine recipients demonstrated a fourfold or greater serologic response to H1N1, H3N2, and influenza B following a single dose of vaccine. During the 1985-1986 influenza B/Ann Arbor epidemic, heterotypic protection afforded by the influenza B/USSR component of trivalent inactivated vaccine was 62% compared with placebo. A single dose of trivalent inactivated vaccine protected school-age children, 6 to 19 years of age, from influenza B infection; the rate of protection was 64% against infection and 73% against febrile illness. PMID- 2330930 TI - An efficacy trial of the rhesus rotavirus vaccine in Maryland. The Clinical Study Group. AB - A double-blind, placebo-controlled trial of oral rhesus rotavirus vaccine at a dose of 10(4) plaque-forming units was performed in 114 young infants in Maryland. Significantly more vaccinees than controls had fever and vomiting during the week after vaccination, but these reactions were mild. Of the vaccinees, 83% had a fourfold or greater rise in neutralizing antibody to rhesus rotavirus vaccine and 69% shed vaccine virus. Seventeen percent of the vaccinees and 24% of controls had rotavirus-positive diarrhea during the 2 years of surveillance. Vaccine efficacy was therefore 29% (95% confidence limits, -31% to +66%). Stools from 12 of 13 episodes containing sufficient antigen to type were serotype 1. We conclude that rhesus rotavirus vaccine was infective, immunogenic, and probably acceptably attenuated but that this serotype 3 vaccine provided little heterotypic protection during serotype 1 outbreaks in the community. PMID- 2330931 TI - Evaluation and treatment of adolescent substance abuse: a decision tree method. AB - A procedure for systematically evaluating and treating adolescents with known or suspected substance abuse is described. Integrating assessment with intervention affords the opportunity to comprehensively characterize the adolescent's problems and to quantitatively monitor treatment progress and outcome. PMID- 2330932 TI - Monitoring parent concerns about teenage drinking and driving: a random digit dial telephone survey. AB - A random telephone survey was conducted in a suburban community in the Washington, D.C. metropolitan area to assess the perceptions of parents about teenage drinking and driving. A total of 807 completed interviews were conducted. The results indicated that while most parents viewed teen drinking (69%) and drinking and driving (65%) to be a prevalent, relatively few seem to be engaging in behaviors likely to influence this. Thirty-two percent said they never discuss drinking and driving with their children, and over 65% said they never talk to other parents about how to talk to their children about drinking and driving, nor have any interest in doing so. Although slightly more than half said they had family policies concerning drinking, less than 20% said there were penalties for violating these policies. Over 70% expressed their willingness to watch a special show on TV about how parents can talk to their children about alcohol. Parents of teenagers appear to be far more likely to think that their teen's friends drink and drive (36%) than they are to think that their teen drinks and drives (10%). The results of this survey indicate a significant lack of parental awareness of teen drinking and a denial of their own teen's involvement in it. PMID- 2330933 TI - How judges sentence DUI offenders: an experimental study. AB - This study examined the impact of 1) a DUI offender's blood alcohol level at the time of arrest and 2) the number of prior drunken driving convictions on judges' sentencing patterns. These variables were manipulated using vignettes that were presented to all judges who sentence drunken drivers in Colorado. Judges were asked to determine appropriate amounts of jail time, fines, public service hours, and alcohol education course work. Results indicated that they gave more severe sentences to offenders with prior records and to those with higher blood alcohol levels. The effects were generally stronger for the first variable, prior record. These findings suggest that judges may perceive of and sentence repeat offenders differently than first-time offenders, regardless of the level of intoxication at arrest. PMID- 2330934 TI - Peer attitudes, sex, and the effects of alcohol on simulated driving performance. AB - This study presents an investigation of the effects of peer attitude, gender, and blood alcohol level on driving performance using a driving simulator. The subjects were 18 male and 18 female social drinkers from the general population, aged 18-25, and holding a current drivers' licence. Subjects were randomly assigned to pro or against drinking driving conditions and tested at different blood alcohol levels. The results revealed that subjects in the for drinking driving condition perceived themselves to be more capable than they actually were and drove increasingly faster and made more mistakes than subjects in the against drinking driving condition when under the influence of alcohol. Significant sex differences were observed only for performance on the driving simulator. Males, in the main, engaged in more dangerous driving and risk taking in simulated driving conditions than females. PMID- 2330935 TI - Alcoholics' attitudes toward and experiences with disulfiram. AB - We studied 345 alcoholic inpatients utilizing a 43-item questionnaire designed to assess these patients' attitudes toward and experiences with disulfiram. A surprisingly high number of patients who had received disulfiram drank ethanol while taking or within 1 week of stopping disulfiram and experienced a disulfiram ethanol reaction. This finding and others derived from the questionnaire are reported, and the potential implications of the findings are discussed. PMID- 2330936 TI - Longitudinal characteristics of hospital use before and after alcoholism treatment. AB - The frequency of inpatient hospital care for three years before and three years after alcoholism treatment was evaluated for a group of 255 patients of predominantly lower socioeconomic status treated for alcoholism at a rural midwestern medical center in 1983. Subjects were interviewed while in treatment to obtain information regarding alcoholism history and demographics. Hospital care was ascertained from an electronic data file of discharges from 172 acute care hospitals throughout the United States and Puerto Rico. One-third of the sample was never hospitalized for an alcohol-related condition in the years prior to or after alcoholism treatment, and 23% of the sample experienced no hospitalizations at all other than the treatment episode when interviewed. The majority of hospital stays before and after treatment were attributed to alcohol abuse. The frequency and total hospital length of stay for alcohol-related admissions increased yearly before treatment, peaked in the year after treatment, and then declined, but not to earliest pretreatment levels. Subjects experienced significantly more hospitalizations and length of stay after alcoholism treatment than before when comparing both the two three-year periods and the immediate 12 months before and after treatment. More frequent hospital care was also significantly associated with higher levels of daily alcohol consumption and drinking duration but not with sociodemographic indicators. PMID- 2330937 TI - "Hello, may we help you?" A study of attrition prevention at the time of the first phone contact with substance-abusing clients. AB - The problem of early attrition from treatment is pervasive throughout community mental health and is particularly high for substance-abusing clients. In spite of the severity of this problem and the potential for successful interventions, there have not been many studies that attempt to reduce the dropout rate of drug abusers. The purpose of this research was to test the effectiveness of attrition prevention procedures at the time of the client's first phone contact with the clinic. Callers were either given an appointment or told to come to the clinic the same day. A second variable was the presence or absence of an experimenter initiated dialogue designed to help subjects predict possible obstacles to attendance and to generate potential solutions to those barriers. Subjects in the same day conditions showed at a higher rate than those given appointments, but the addition of the dialogue had no effect on client behavior. The results are discussed in terms of how mental health professionals can find cost effective interventions that prevent drug abuse treatment dropout. PMID- 2330938 TI - A social bonding-drug progression model of amphetamine use among young women. AB - Social bonding theory explains less serious drug use better than use of hard drugs. The difference in prediction may be due to the omission of intervening variables between the bond and serious drug use, such as experience with minor drugs. In this study the impact of the social bond on amphetamine use is examined among a national sample of high school senior women. Included in the model is the notion of drug progression, in which individuals first use minor drugs and progress to illicit drugs. To ascertain whether the bond is mediated through use of less serious drugs, cigarettes, alcohol, and marijuana are utilized in the analysis. Among the bonding variables, religious commitment has the only significant direct effect on amphetamines. Overall, elements of the bond explain less variance in amphetamines than in cigarettes, alcohol, and marijuana. Combining drug progression with social bonding theory substantially increases the explained variance of amphetamines. PMID- 2330939 TI - Factors in mortality by drug dependence among Puerto Ricans in New York City. AB - This paper presents data on mortality by drug dependence among Puerto Rican residents aged 15-44 of New York City. While men show death rates for drug dependence several times those of women, when deaths by drug dependence are calculated as a proportion of all deaths, the ratios are nearly the same for both sexes. Factors relevant to analyzing mortality statistics on drug dependence in this population are an undercount of Puerto Rican males and competing causes of death, particularly homicide among men. Factors influencing deaths by drugs are gender roles as they influence patterns of drug use and types of chronic use: regular and intermittent. PMID- 2330940 TI - A computer model for the evaluation of the effect of corneal topography on optical performance. AB - We developed a method that models the effect of irregular corneal surface topography on corneal optical performance. A computer program mimics the function of an optical bench. The method generates a variety of objects (single point, standard Snellen letters, low contrast Snellen letters, arbitrarily complex objects) in object space. The lens is the corneal surface evaluated by a corneal topography analysis system. The objects are refracted by the cornea by using raytracing analysis to produce an image, which is displayed on a video monitor. Optically degraded images are generated by raytracing analysis of selected irregular corneal surfaces, such as those from patients with keratoconus and those from patients having undergone epikeratophakia for aphakia. PMID- 2330941 TI - A 16-year study of conjunctival dacryocystorhinostomy. AB - We reviewed a consecutive series of 79 conjunctival dacryocystorhinostomies performed over a 16-year period in 75 patients. Thirty-eight of 75 patients with canalicular blockage between the common canaliculus and the first 5 mm of the canaliculus as well as patients with common canalicular blockage who had failed previous dacryocystorhinostomy were treated with combined canalicular reconstruction, nasal lacrimal intubation, and conjunctival dacryocystorhinostomy. In 37 patients, less than 5 mm of proximal canaliculus remained open. These patients were treated with conjunctival dacryocystorhinostomy alone, including four patients who had bilateral procedures. Two of 38 patients who underwent combined canalicular and conjunctival procedures required further surgery for a successful outcome compared with 14 of 37 patients who underwent conjunctival dacryocystorhinostomy without canalicular reconstruction (P = .002). Overall, 71 of 74 patients (96%) had a successful outcome, and five patients were lost to follow-up. PMID- 2330942 TI - Acute scleritis in porphyria cutanea tarda. AB - We examined three patients who had dermatologic and biochemical manifestations of porphyria cutanea tarda and localized thinning or excavation in the sun-exposed interpalpebral sclera, adjacent to the cornea. All three patients had signs of acute scleritis. The acute scleritis responded to oral indomethacin in one patient, but systemic corticosteroids were required to control the inflammation in the other two patients. Phlebotomy, protection from sunlight, and refraining from alcohol played an important part in the treatment of the patients. PMID- 2330943 TI - Adjunctive use of delayed and adjustable low-dose 5-fluorouracil in refractory glaucoma. AB - We used delayed 5-mg subconjunctival injections of 5-fluorouracil as an adjunct to filtering surgery in ten eyes with refractory glaucoma. The first 5 fluorouracil injection was made three to 15 days postoperatively and was used only when clinical signs suggested an impending bleb failure. These signs included flattening and localization of bleb, increased vascularity, early subconjunctival scarring, loss of microcystic conjunctival changes, and increased intraocular pressure. After a follow-up of ten to 17 months (mean, 13.7 months), an intraocular pressure of less than 21 mm Hg was attained in five eyes without medication and in four eyes with medication. The treatment failed in one eye. The average dose of 5-fluorouracil was 28 +/- 12 mg per eye. There were no conjunctival wound leaks. Six eyes developed transient corneal epithelial defects. The modified administration of 5-fluorouracil can result in fewer conjunctival wound leaks. Its use can be limited to those patients who show evidence of impending bleb failure. PMID- 2330944 TI - A refractive and histopathologic study of excimer laser keratectomy in primates. AB - Using a 193-nm excimer laser, we produced wide-area, refractive keratectomies on 18 cynomolgus monkey corneas and followed them up for up to 18 months. All corneas developed some subepithelial haze by one month. Electron microscopy disclosed epithelial thickening, absence of Bowman's layer, and subepithelial activated fibroblasts surrounded by disorganized collagen. By six months, the haze faded to a variable degree, the epithelium regained normal thickness, and the collagen was more organized. Persistent corneal haze at 12 months in some corneas correlated with electronlucent spaces in the subepithelial zone. Corneas were 90 microns thinner centrally two weeks after myopic ablation, but returned to preoperative thickness by six months. Myopic flattening and hyperopic steepening of 6 diopters were targeted, and over 7 diopters of each were achieved initially. Regression of induced curvature stabilized over several months. At 18 months, 4.4 diopters of myopic flattening and 5.2 diopters of hyperopic steepening remained. PMID- 2330945 TI - Spontaneous visual recovery from traumatic optic neuropathy after blunt head injury. AB - Four patients who developed immediate blindness (no light perception) after indirect traumatic optic neuropathy caused by blunt head injury recovered vision without surgical intervention. In one patient, whose affected eye recovered to a visual acuity of 20/50 + 2, corticosteroids were not used. In two of the other patients, visual recovery began before corticosteroids were instituted. One patient recovered a visual acuity of R.E.: 20/15, one recovered a visual acuity of L.E.: 20/25-2, and one recovered a visual acuity of R.E.: 20/200 but with useful temporal field vision. Many investigators advocate aggressive surgical therapy for indirect neuropathy, particularly when corticosteroids fail. Significant recovery may occur despite no light perception, however, with medical therapy or even without therapy. PMID- 2330947 TI - Bilateral choroidal neonatal neuroblastoma. AB - We treated a bilateral, well-differentiated neuroblastoma of the choroid in a patient who had congenital abdominal neuroblastoma. Although orbital metastasis of neuroblastoma is common, intraocular metastasis is not. In our patient, there was no amplification of the N-myc oncogene in the tumor of either eye. This is consistent with early-stage primary neuroblastoma. Histologically, the tumors were identical in each eye and well differentiated with Homer Wright rosettes; most neuroblastoma metastases have few rosettes and are composed of more undifferentiated, anaplastic cells. We believe that our patient had bilateral primary tumors and not metastatic tumors. PMID- 2330946 TI - Analysis of 135 autopsy eyes for ocular involvement in leukemia. AB - To explain the marked variation in the reported incidence of how often leukemic cells infiltrate the eye in fatal cases of leukemia, we tested the hypothesis that ocular leukemic infiltration is related to the peripheral leukocyte count during the final hours of life. We reviewed tissue sections, as well as autopsy and clinical records, from 135 patients who had fatal leukemia and had their eyes examined after death at Duke University Medical Center. Infiltrates of leukemic cells were found in the eyes of 42 of 135 patients (31.1%), with the choroid being the most frequently involved site. We detected a significant positive correlation between the ocular leukemic infiltration and an agonal leukocyte count as well as the severity of systemic disease. Differences in the agonal circulating leukocyte count may partly explain variations in the incidence of leukemic infiltrates in different postmortem studies. PMID- 2330948 TI - Ocular and systemic findings in the Aarskog (facial-digital-genital) syndrome. AB - The Aarskog (facial-digital-genital) syndrome is an X-linked disorder in which short stature is accompanied by hypertelorism, digital anomalies, and shawl scrotum. Except for hypertelorism and blepharoptosis, ophthalmic abnormalities have been rarely noted in this condition. We examined four patients who had Aarskog syndrome and unilaterally or bilaterally decreased vision on initial examination. Three family members had V-pattern esotropia, latent nystagmus, inferior oblique overaction, and amblyopia. A fourth patient had bilateral blepharoptosis and severe astigmatism. Other ocular features included hyperopia, anisometropia, deficient ocular elevation, blue sclerae, and posterior embryotoxon. These findings underscore the need for ophthalmic examination in asymptomatic patients with Aarskog syndrome to rule out treatable causes of visual loss. PMID- 2330949 TI - Electroretinograms in microcephaly with chorioretinal degeneration. AB - We recorded full-field electroretinograms from a family with two daughters with microcephaly and chorioretinal degeneration and a third daughter and mother with microcephaly without chorioretinal degeneration. The two siblings with inferior chorioretinal degeneration showed electroretinographic responses to 0.5-Hz white light that were reduced 60% to 70% below normal, suggesting that the loss of photoreceptor function exceeded the areas of visible atrophy. The mother and third daughter had normal electroretinograms. The two siblings, ages 12 and 21 years, had virtually the same electroretinographic amplitudes. In a second family, a man with microcephaly and inferior chorioretinal degeneration, examined at ages 9 and 23 years, also showed 60% to 70% reduction in electroretinographic responses to 0.5-Hz white light and showed no change in amplitudes over the 14 year interval. These findings suggest that the chorioretinal degeneration sometimes associated with microcephaly is stable in young adult life, although the long-term prognosis remains to be defined. PMID- 2330950 TI - Clinical and histologic effects of extreme intraocular hypothermia. AB - Rabbit eyes in which vitrectomy was performed underwent three hours of hypothermic perfusion with either 22 C or 2 C lactated Ringer's solution. Clinical, electroretinographic, fluorescein angiographic, histologic, and ultrastructural examinations were performed. No changes were noted in eyes cooled with 22 C fluid. Reversible lens opacities, equivocal electroretinographic changes, and subclinical retinal detachments were found in the eyes cooled with 2 C fluid. Extreme cooling of eyes is not advisable, although temperatures of 22 C are well tolerated. PMID- 2330951 TI - What is the evidence and medical advertising. PMID- 2330952 TI - Fatigue-induced familial anisocoria. PMID- 2330953 TI - The effect of light intensity on measurement of the relative afferent pupillary defect. PMID- 2330954 TI - Bleeding complications in thrombocytopenic patients undergoing ophthalmic surgery. PMID- 2330955 TI - Cold-induced corneal edema as an isolated feature of trigeminal neuropathy. PMID- 2330956 TI - Superior corneal thinning with pellucid marginal corneal degeneration. PMID- 2330957 TI - Episcleritis and symblepharon associated with Lyme keratitis. PMID- 2330958 TI - A technique for fixing posterior chamber intraocular lenses to the iris through a corneoscleral incision. PMID- 2330959 TI - Posterior subcapsular cataracts associated with nasal or inhalation corticosteroids. PMID- 2330960 TI - A contraindication to injection of intravenous fluorescein. PMID- 2330961 TI - The effects of keyguard use and pelvic positioning on typing speed and accuracy in a boy with cerebral palsy. AB - The effects of keyguard use and pelvic positioning (neutral versus posterior tilt) on typing proficiency was studied in an 8-year-old boy with athetoid and spastic cerebral palsy. Speed and accuracy were measured with the Mastertype computer software program (Zweig, 1984). The results showed that the use of a keyguard increased the subject's typing accuracy and decreased his speed. Neither neutral nor posterior pelvic positioning appeared to have a significant effect on typing speed or on accuracy. PMID- 2330962 TI - Quality of time use by adults with spinal cord injuries. AB - The self-perceived quality of time use of 15 community-based adults with spinal cord injuries was compared with that of 12 age- and sex-matched nondisabled adults through the use of the Activity Configuration Log (modified from an unpublished clinical assessment developed by Claudia Allen). Differences in how subjects classified their daily occupations were found between and within groups, especially for the categories of Work, Self-Maintenance, and Other. The results suggest that the subjects' classifications of occupations and interpretations of their meanings are important sources of information for both the science of occupation and occupational therapy practice. The subjects with spinal cord injuries had a high rate of unemployment (67%) and much more daily free time than did their nondisabled counterparts. The affective quality of particular occupations was found to be related to the affective quality of the entire day. Occupational therapists agreed more with each other than with the subjects with disabilities when classifying occupations. Implications for practice and research are provided. PMID- 2330963 TI - Use of an elbow restraint to improve finger-feeding skills in a child with Rett syndrome. AB - A single-subject study with an ABAB design was conducted to examine the effectiveness of an elbow restraint splint in improving the functional band use of a child with Rett syndrome. The intervention consisted of the child's wearing an elbow restraint on her nondominant (left) arm during snack time. Her ability to finger-feed cereal from a bowl was evaluated across four phases. An analysis of the data revealed only modest improvements in the amount of cereal consumed and in the time required to complete the eating task. Variability in the subject's performance made visual interpretation of the data difficult. The findings, however, were in the anticipated direction and provide indications for future research. PMID- 2330964 TI - The reliability of goniometric measurements of active and passive wrist motions. AB - A reliability study was conducted to determine (a) the intrarater and interrater reliability of goniometric measurement of active and passive wrist motions under clinical conditions and (b) the effect of a therapist's specialization on the reliability of measurement. Randomly paired therapists performed repeated measurements of active and passive wrist motions in 48 subjects who had been referred to one of four occupational therapy or hand management clinics for evaluation and treatment. The data were analyzed with an intraclass correlation coefficient. A posteriori data analyses were performed to determine the effects of identified sources of error on the reliability of measurement. The results indicated that measurement of wrist motion by individual therapists is highly reliable and that intrarater reliability is higher than interrater reliability for all active and passive motions. Interrater reliability was generally higher among specialized therapists for reasons not immediately apparent from this study. With the exception of pain, identified sources of error were found to have surprisingly little effect on the reliability of measurement. PMID- 2330965 TI - Research attitudes and activities of occupational therapy clinicians. AB - Two hundred and seventy occupational therapy clinicians, whose primary or secondary employment function was in direct patient service, were surveyed to determine their perceived roles and attitudes regarding research. Results showed a strong belief in the importance of research in the profession, yet minimal involvement in research due to limited time, money, and skill. The role of collaborator with experienced researchers was rated as highly desirable. Few clinicians indicated no interest in research. Implications of the results and suggestions for strategies to increase clinicians' involvement and satisfaction in research through mutual experiences and continuing education are given. PMID- 2330966 TI - Teaching the patient with cognitive deficits to use a computer. PMID- 2330967 TI - The dilemma of part-time career patterns. PMID- 2330968 TI - Volume homeostasis in calves with artificial atria and ventricles. AB - We examined whether replacement of cardiac atria and ventricles with total artificial hearts (TAH), a procedure that removes cardiac nerves and all sources of atrial natriuretic factor (ANF), would cause alterations in volume homeostasis in awake calves. Preoperatively, extracted plasma immunoreactive (ir)ANF levels were 13.3 +/- 0.6 and remained postoperatively at 10.5 +/- 0.4 pg/ml (P less than 0.01). TAH implantation caused systemic and pulmonary hypertension (P less than 0.01), salt retention, edema, and significant elevations of plasma renin, aldosterone, and arginine vasopressin. In intact calves rapid infusion of 6 liters of normal saline raised irANF levels to 73.7 +/- 6.5 pg/ml (P less than 0.01) and elicited a large natriuresis and diuresis. No such response to 6 liters of normal saline was obtained after calves had recovered from TAH implantation. Reduction of cardiac output (CO) by 50% caused further salt retention and no change in irANF levels. Elevation of CO back to and 33% above base line produced only a diuresis, whereas salt retention persisted and irANF levels remained unchanged. The same maneuvers elicited in surgical control calves (artificial ventricles only, largely intact atria) a significant increase in irANF levels and a diuresis and natriuresis. In conclusion, alterations in volume homeostasis observed after TAH implantation seem to be the consequence of at least two pathophysiological mechanisms: 1) functional ANF "deficiency," characterized by apparently unregulated ANF secretion from noncardiac sites, and 2) cardiac denervation. PMID- 2330969 TI - Peritubular capillary permeability and intravascular RBC aggregation after ischemia: effects of neutrophils. AB - The influence of neutrophils on peritubular capillary permeability and intravascular red blood cell (RBC) aggregation after renal ischemia was studied in anesthetized Sprague-Dawley rats. Intraperitoneal administration of antineutrophil serum (ANS) reduced the number of neutrophils in the blood to 3% of normal. The control group received an equal volume of inactive serum. Renal macromolecular capillary permeability was studied from 1) extravasation of albumin and 2) plasma to lymph transport of plasma proteins and of neutral and negatively charged lactate dehydrogenase (LDH). The net driving force (NDF) for fluid transfer over the peritubular capillary membrane was determined by the micropuncture technique. The intrarenal distributions of neutrophils and RBC were measured by a histochemical method and 51Cr-labeled RBC, respectively. Under preischemic control conditions neither macromolecular permeability nor renal clearance of inulin was affected by ANS. However, the steep increase in the macromolecular transport from plasma to lymph resulting from 45 min of ischemia and reperfusion was blunted by ANS, and preischemic control values were restored after 1 h of recirculation. In the control group the mass transport of plasma proteins increased twofold and that of both neutral and negatively charged LDH fourfold. NDF was equal in the two groups. In the ANS-treated animals the intrarenal neutrophil content was only 2% of the control. Neutrophils were found mainly in the cortex, whereas RBC aggregation was observed only in the renal medulla. It is concluded that neutrophils mediate postischemic capillary leakage. It is suggested that this leakage underlies RBC aggregation and incomplete return of blood flow in the renal medulla after ischemia. PMID- 2330970 TI - Acute and subacute prostaglandin and ANG II inhibition on glomerulotubular dynamics in rats. AB - Prostaglandins (PG) and angiotensin II (ANG II) contribute to regulation of glomerular microcirculation. Acute vs. chronic physiological alterations of glomerular hemodynamics that result from inhibition of either PG or ANG II, or both, and their interaction were examined. Four groups of Munich-Wistar rats were submitted to the following micropuncture studies in euvolemic conditions for measurements of glomerular hemodynamics and tubular fluid reabsorption: 1) an untreated control group, 2) 4- to 6-day inhibition of both PG and angiotensin converting enzyme activity with meclofenamate and MK-421 (enalapril), 3) 4- to 6 day treatment with enalapril followed by acute PG inhibition in the second measurement period, 4) 4- to 6-day PG inhibition followed by acute enalapril treatment in the second period. Dual 4- to 6-day treatment decreased single nephron filtration rate (SNGFR, 24 +/- 2 vs. 33 +/- 2 nl/min in control; P less than 0.05) as a result of decreases in single-nephron plasma flow (SNPF) and glomerular hydrostatic pressure gradient (delta P). Treatment with enalapril alone for 4-6 days did not reduce SNGFR and SNPF; however, delta P decreased. Acute addition of meclofenamate did not alter these factors. SNGFR was decreased with 4- to 6-day treatment of meclofenamate from 33 +/- 2 in control to 25 +/- 1 nl/min (P less than 0.05). Acute treatment with enalapril in the 4- to 6-day meclofenamate-treated rats increased SNGFR to values not different from control. The results demonstrated that glomerular hemodynamic alterations consequent to inhibition of ANG II and PG systems differ between chronic and acute treatments. Therefore, interpretation of the role of individual hormonal systems in the control of glomerular hemodynamics should be approached with caution, since effects may be altered by duration of treatment and involvement of other vasoactive systems. PMID- 2330971 TI - Basolateral transport of lactate in dog thick ascending limbs. AB - Basolateral membrane vesicles (BLMV) isolated from both red outer medulla or from thick ascending limb segments isolated from the dog kidney were used to examine the process of lactate transport in this nephron segment. The BLMV preparation was enriched in Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) that represented 96% of the total ATPase activity of this preparation and the vesicles were largely under the right side-out orientation. On application of a OH- or HCO3- gradient (inside greater than outside), a secondary active lactate accumulation was observed, with characteristic transient overshoot. This phenomenon was shown to occur irrespective of the presence or absence of Na+, K+, or Cl-. The pH, but not the bicarbonate-driven, overshoot was abolished by nigericin (in presence of K+). Studies with valinomycin and K+ demonstrated that the generation of a membrane potential was not responsible for the acceleration of lactate transport, even if the amplitude of lactate accumulation was reduced in the presence of a bicarbonate gradient and valinomycin. A significant trans stimulation of [14C]lactate transport by cold lactate was observed (under voltage clamp condition). The transport was 4-acetamido-4'-isothiocyanostilbene-2,2' disulfonic acid insensitive but sensitive to furosemide (IC50 = 0.1 mM) and alpha hydroxycyanocinnamate (IC50 = 1 mM). The kinetic parameters of the transporter revealed a single carrier with an apparent Michaelis constant of 1.7 mM and an apparent Vmax of 9.7 nmol.mg protein-1.30 s-1. The transporter was shown to be distinct from that of proximal tubule brush-border membrane or mitochondria (pyruvate). Thus thick ascending limbs possess a carrier-mediated lactate transport that can be used for lactate uptake (aerobic condition) or for lactate release (anaerobic glycolysis) according to metabolic processes imposed by the local oxygenation condition. PMID- 2330972 TI - Osmoregulation of betaine transport in mammalian renal medullary cells. AB - Escherichia coli and Staphylococcus typhimurium are known to accumulate betaine by increased transport when extracellular osmolality rises. In the present studies a similar process is demonstrated in mammalian cells. Renal medullary cells contain high concentrations of "compatible" organic osmolytes such as betaine, myo-inositol, sorbitol, and glycerophosphorylcholine. The organic osmolytes occur as an osmoregulatory response to the high and variable interstitial NaCl concentration that is part of the urinary concentrating mechanism. Dog kidney cells in culture (MDCK) were previously shown to accumulate betaine in response to increased extracellular osmolality. We demonstrate here that this accumulation requires the presence of betaine in the medium, and this apparently is a result of uptake of extracellular betaine, rather than synthesis by the cells. MDCK cells have low- and high-affinity sodium-dependent betaine transporters with Km for betaine of approximately 6 and approximately 0.1 mM, respectively. Relative to isotonic controls, sodium-dependent betaine uptake is approximately sevenfold greater in cells chronically exposed (greater than 1 yr) to hypertonic medium (615 mosmol/kg). This is due to an increase in the maximal velocity of sodium-dependent betaine uptake with no apparent change in Km. Cells acutely exposed (1-7 days) to hypertonic medium show increased sodium-dependent betaine uptake, which is maximal after 1 day, then decreases as betaine and other osmolytes accumulate in the cells. Thus the response by which renal cells accumulate betaine following hypertonicity apparently includes an increase in the number (or, less likely, the transport turnover rate) of functioning sodium dependent betaine transporters. PMID- 2330973 TI - Alanine protects rabbit proximal tubules against anoxic injury in vitro. AB - Rabbit proximal tubules were incubated aerobically or subjected to anoxia for 30 min followed by 60 min of reoxygenation. The medium contained (in mM) 5 glucose, 10 butyrate, 4 lactate or alpha-ketoglutarate (alpha-KG), and 1 alanine. Anoxic tubules in this medium were severely injured and recovered poorly. If the incubation medium was supplemented with additional alanine (up to 2.5 or 5 mM), then anoxic injury was prevented almost completely. Tubules in high-alanine medium showed modest elevations of ATP during anoxia. Comparable elevations of ATP were induced in anoxic tubules incubated with 4 mM alpha-KG and 5 mM aspartate without alanine. These substrates are metabolized anaerobically in the mitochondria to yield ATP. Surprisingly, anoxic tubules with alpha-KG and aspartate showed severe injury despite elevated ATP. If 5 mM alanine was also present, then additional increments of ATP did not occur, but injury was prevented. Examination of glucose metabolism failed to provide evidence for stimulation of anaerobic fermentations by alanine. These results suggest that alanine-induced cytoprotection during anoxia occurs by mechanisms not related to ATP synthesis, and that elevated ATP in alanine-supplemented tubules may be a result and not the cause of protection. Cytoprotection by alanine was shown to last for less than or equal to 90 min of anoxia. Glycine, a structurally related amino acid, also protects anoxic proximal tubules (J. Clin. Invest. 80: 1446, 1987). The mechanisms that underlie the cytoprotective effects of alanine and glycine remain to be determined. PMID- 2330974 TI - Role of prostaglandins in the renal response to calcium infusion. AB - The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca.kg-1.min-1) on renal hemodynamics and on renal excretory function were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 min each (1 ml/min). In a second group, the same doses were administered 30 min after the start of an infusion of prostaglandin (PG) inhibitors (intrarenal indomethacin, 10 micrograms.kg-1.min-1, or intravenous bolus injection of meclofenamate, 5 mg/kg). No change with physiological significance was observed during the infusion of 10 micrograms Ca.kg-1.min-1. However, the infusion of 100 micrograms Ca.kg-1.min-1 induced increases (P less than 0.05) in glomerular filtration rate (50%), sodium excretion rate (180%), and fractional excretion of sodium (160%), with respect to control precalcium values. All these changes were prevented by the concurrent administration of PG synthesis inhibitors. Urinary PGE2 and 6-keto-PGF1 alpha increased 220 and 85%, respectively, during the infusion of 100 micrograms Ca.kg-1.min-1, but both decreased (P less than 0.05) below basal levels during the concurrent administration of PG synthesis inhibitors. The infusion of 100 micrograms Ca.kg 1.min-1 decreased (P less than 0.05) renal blood flow by 16% during the administration of PG synthesis inhibitors. These results suggest that PGs are mediating the increase in hemodynamic and excretory factors induced by the intrarenal infusion of 100 micrograms Ca.kg-1.min-1. PMID- 2330975 TI - Does lithium clearance reflect distal delivery in humans? Analysis with furosemide infusion. AB - Fractional excretion of lithium (FELi+) has been proposed as an index of fluid delivery to the distal nephron. The increase in FELi+ after the "loop diuretic" furosemide indicates that this postulate may not be valid unless furosemide acts in the proximal tubules. We studied the effect of furosemide (40 mg iv as bolus, followed by 20 mg/h infusion for 90 min) in eight healthy male subjects during maximal water diuresis. Special care was taken to exactly replace urinary losses. Furosemide greatly increased fractional excretion of sodium, from 1.3 +/- 0.4 to 27.8 +/- 3.9%, and water, from 14.2 +/- 1.7 to 38.2 +/- 3.7% (P less than 0.01). There was a disproportionately large increase in FELi+ from 30.3 +/- 3.0 to 53.7 +/- 2.9% (P less than 0.01), whereas fractional excretion of some other alleged proximal markers increased to a lesser extent. Lysine vasopressin, infused at the end of the experiment (n = 7), caused only a small increase in urine osmolality from 225 +/- 17 to 241 +/- 17 mosmol/kg (P less than 0.01), indicating that medullary hyperosmolality had been largely abolished. The most likely explanation of these results is that furosemide has a moderate action in the proximal tubules, and at the same time inhibits preexistent lithium absorption in Henle's loop. In addition, the large difference between FELi+ and maximal urine flow remaining after furosemide suggests that, despite the decreased medullary osmotic gradient, water backdiffusion is unaltered by furosemide or that lithium concentration in the proximal tubule is changed by furosemide. PMID- 2330976 TI - Urea transport in a distributed loop model of the urine-concentrating mechanism. AB - Continuously distributed loops of Henle were used in a central core model of the rat kidney's urine-concentrating mechanism to investigate the importance of overlapping loops for three different modes of urea transport in the long loops of Henle: 1) urea-impermeable loops, 2) urea-permeable loops (as indicated by perfused tubule experiments), and 3) loops with urea-permeable descending limbs and active urea transport out of thin ascending limbs. Mode 1 produces high papillary tip osmolality in accordance with tissue slice experiments, but the relative contribution of urea to the osmolality of the central core and the long descending limbs is below experimental measurements. Mode 2 generates no significant osmolality increase in the inner medulla, in agreement with other model studies. Mode 3 produces high papillary tip osmolality with a substantial contribution of urea to the osmolality of the core and the descending limbs, which is more in accordance with experiments. The results suggest that 1) overlapping loops may produce a cascade effect that contributes to the inner medullary concentrating mechanism and that 2) new experiments are needed to more certainly ascertain the urea transport characteristics of the thin ascending limbs. PMID- 2330977 TI - Sodium-23 nuclear magnetic resonance imaging of the rabbit kidney in vivo. AB - The mechanism by which the mammalian kidney generates a concentration gradient of sodium from cortex to papilla is still not entirely understood. Studies of how the kidney as an organ generates this gradient have been hampered by the lack of a noninvasive method for monitoring the intrarenal sodium distribution. Herein, we demonstrate the value of sodium-23 nuclear magnetic resonance (23Na-NMR) imaging to nondestructively assess the intrarenal sodium distribution. 23Na-NMR images were obtained from a surgically exposed kidney preparation that showed the two-dimensional distribution of sodium in the rabbit kidney. In the antidiuretic kidney this gradient resulted in papillary sodium concentrations that were approximately threefold higher than cortical values. Serial 23Na-NMR images obtained during saline infusion demonstrated the kinetics by which the sodium gradient increases with diuresis. The half-time for 23Na washout of the medulla of the kidney was approximately 6 min with this protocol. In addition, a three dimensional data set of the sodium distribution of the kidney was obtained with voxel dimensions of 1.5 mm3 by use of a three-dimensional 23Na-NMR imaging technique. Without surgical exposure, 23Na-NMR images of the rabbit kidney were collected under completely noninvasive conditions by use of a surface coil. The 23Na-NMR signal from the kidney was easily detected; however, to obtain images of comparable signal-to-noise ratio to the surgically exposed kidney, spatial and temporal resolution were significantly reduced. PMID- 2330978 TI - Effect of dopamine on the tubuloglomerular feedback mechanism. AB - Experiments were performed in anesthetized rats to examine whether infusion of dopamine is associated with a reduction in the tubuloglomerular feedback (TGF) response of stop-flow pressure (PSF) and early proximal flow rate (VEP) to increases of loop of Henle flow. The purpose of these studies was to test further the validity of the proposal that renal vasodilation is a nonspecific cause for diminished TGF responsiveness. When femoral arterial pressure was kept constant with a suprarenal aortic clamp, intravenous infusion of dopamine at rates of 4, 15, 35, and 75 micrograms.kg-1.min-1 induced a 10.9, 23.4, 31.3, and 30.1% decrease in renal vascular resistance. Maximum PSF and VEP responses were significantly reduced at all dose levels of dopamine, whereas V1/2, the flow rate required to produce the half-maximum response, was not altered. TGF blunting occurred within less than 10 min after starting the dopamine infusion. Peritubular infusion of dopamine reduced maximum PSF responses from 8.8 +/- 0.7 to 4.6 +/- 0.53 mmHg at 10(-4) M (P less than 0.01) and from 6.0 +/- 1.19 to 3.6 +/- 0.55 mmHg at 10(-3) M (P less than 0.05). The results are consistent with the notion that renal vasodilatation may modify TGF responses by preventing the full vasoconstrictor response to changes in luminal NaCl concentration. PMID- 2330979 TI - Role of renal nerves in regulation of vasopressin secretion and blood pressure in conscious rabbits. AB - The observation that electrical stimulation of the renal nerves increases vasopressin secretion raises the possibility that the renal nerves may participate in the control of vasopressin secretion. In the present investigation, the effects of renal denervation on the vasopressin response to two reflex stimuli (nitroprusside infusion and hemorrhage) and two osmotic stimuli (hypertonic saline infusion and water deprivation) were studied in conscious, chronically prepared rabbits. Nitroprusside infusion in 13 intact and 14 denervated rabbits caused similar decreases in mean arterial pressure (MAP) and the increase in plasma arginine vasopressin concentration (PAVP) in intact (2.6 +/- 0.3 to 5.8 +/- 0.9 pg/ml, P less than 0.01) and denervated (2.8 +/- 0.3 to 5.7 +/- 1.3 pg/ml, P less than 0.01) rabbits was not significantly different. Hemorrhage (20 ml/kg) in 15 intact and 14 denervated rabbits caused similar decreases in MAP. Again, the increase in PAVP from 2.7 +/- 0.3 to 159.0 +/- 37.1 pg/ml (P less than 0.01) in intact and from 5.0 +/- 1.7 to 115.4 +/- 45.6 pg/ml (P less than 0.01) in denervated rabbits was not significantly different, nor was the relationship between PAVP and MAP in the two groups. In seven intact rabbits, hypertonic saline infusion increased PAVP from 4.0 +/- 0.9 to 10.9 +/- 2.8 pg/ml (P less than 0.05). The change in six denervated rabbits was not significantly different, nor was the relationship between PAVP and plasma osmolality. During water deprivation (24 h) in six intact rabbits, PAVP increased from 4.0 +/- 0.7 to 6.9 +/- 0.6 pg/ml (P less than 0.05). Again, the increase in PAVP in six denervated rabbits was not significantly different from that in the intact rabbits. The change in MAP during water deprivation in the two groups was also not significantly different. Renal cortical norepinephrine concentration in denervated kidneys was less than 10 ng/g wet wt. These results indicate that, in conscious rabbits, renal denervation does not impair the osmotic or reflex regulation of vasopressin secretion, nor does it interfere with blood pressure regulation during hypovolemia or hypotension. PMID- 2330980 TI - Na(+)-dependent biotin transport into brush-border membrane vesicles from rat kidney. AB - The mechanisms of biotin reabsorption in rat kidney cortex were investigated using isolated brush-border membrane vesicles. An inwardly directed Na+ gradient specifically stimulated a transient biotin overshoot. Biotin transport was not affected by a valinomycin-induced K(+)-diffusion potential, and biotin(-)-Na+ stoichiometry was found to be 1:1. As a function of concentration, the uptake showed saturation in the presence of a Na+ gradient with an apparent Michaelis constant (Km) of 55 microM and Vmax of 217 pmol.mg protein-1.25 s-1. Desthiobiotin, 250 microM, norbiotin, bisnorbiotin, thioctic acid, valeric acid, probenecid, and nonanoic acid inhibited the transport of 30 microM biotin, whereas other biotin derivatives, as well as biocytin and organic acids found in the urine of biotinidase-deficient patients, did not. Preloading of the vesicles with biotin, desthiobiotin, norbiotin, and thioctic acid in the presence of Na+ increased initial uptake of biotin from the incubation medium (trans stimulation). Our results indicate that biotin absorption in rat kidney fulfills the criteria for a specific carrier-mediated and electroneutral Na(+)-biotin- cotransport in a 1:1 ratio. The results are discussed in context with congenital biotinidase deficiency in humans. PMID- 2330981 TI - Sex differences in autoregulation of juxtamedullary glomerular blood flow in hydronephrotic rats. AB - The technique of the split hydronephrotic kidney of anesthetized Wistar rats was used for the first time to study afferent and efferent arterioles of juxtamedullary (JM) glomeruli in vivo and to compare their behavior with that of the cortical glomeruli in female (F, 270 g body wt) and male (M, 400 g body wt) rats. The mean length of cortical efferent arterioles (F, 260; M, 380 microns) was less than 10% the length of JM efferent arterioles. Luminal diameters of the JM afferent arteriole (F, 17.1; M, 18.3 microns) and efferent arteriole (F, 25; M, 33.4 microns) were much larger than those of cortical arterioles (afferent: F, 9.1, M, 10.5 microns; efferent: F and M, 11.1 microns). In the hydronephrotic kidney, cortical glomerular blood flow (F, 17.5; M, 18.3 nl/min) is much reduced compared with the normal filtering kidney. This, however, is not true of JM glomerular blood flow (F, 120; M, 262 nl/min). During the reduction of renal perfusion pressure in females blood flow was autoregulated in cortical glomeruli within the pressure range of 110 to 80 mmHg; JM glomeruli failed to show any autoregulation. In males the glomerular blood flow was similarly autoregulated down to 90 mmHg in both cortical and JM nephrons. Local application of indomethacin to the kidneys from female rats reduced the glomerular flow rates by 30% but changed the autoregulatory behavior of cortical and JM glomerular blood flow so that it resembled that observed in untreated males. The data suggest that in females the autoregulatory response, particularly in JM glomeruli, is modified by prostaglandins. PMID- 2330982 TI - Dietary bicarbonate reduces rat distal nephron acidification evaluated in situ. AB - Whether altered reabsorption of bicarbonate by the superficial distal nephron contributes to the renal response to a chronic dietary bicarbonate challenge is not known. These micropuncture studies were done in control, NaHCO3-loaded, and NaCl-loaded Munich-Wistar rats to determine whether this dietary maneuver altered acidification in this nephron segment as evaluated in situ. Urinary bicarbonate excretion of NaHCO3-loaded animals was higher than control for each day of a 7 day study period, but bicarbonate excretion for animals identically loaded with NaCl was not sustained above control. Bicarbonate transport by the superficial distal nephron was assessed using paired collections from this segment. Net bicarbonate reabsorption was observed in all three groups. Reabsorption was lower in NaHCO3-loaded vs. control (11 vs. 25 pmol/min, P less than 0.01) but that for NaCl-loaded animals was not. The data indicate that reduced reabsorption of bicarbonate by the superficial distal nephron of rats contributes to the renal response to a chronic dietary bicarbonate challenge as evaluated in situ. PMID- 2330983 TI - Apical acidification by rabbit papillary surface epithelium. AB - The rabbit papillary surface epithelium (PSE) is a simple cuboidal epithelium that covers the outer surface of the renal papilla and has an apical surface that faces the urinary space. We studied acid-base transport in this epithelium by dissecting it from the papilla, mounting it in a modified Ussing chamber, and following pH changes in the apical bathing solution. The experiments demonstrated that the PSE is capable of acidifying the apical solution at a substantial rate. The acidification rate was similar with 100% nitrogen and 100% oxygen (with and without 10 microM antimycin A), ruling out a dependence on oxidative metabolism. Addition of 1 mM iodoacetate decreased apical acidification by 55%, suggesting a dependence on glycolysis. The net rate of lactate secretion was only 17% of the total acid secretion rate, indicating that apical acidification was not directly caused by secretion of lactic acid alone. Removal of sodium or potassium from the apical solutions or the addition of 1 mM N-ethylmaleimide failed to eliminate the apical acidification. Although the rate of PSE apical acidification is comparable to that of the rabbit outer medullary collecting duct (on a unit surface area basis), its contribution to urinary net acid excretion is likely to be small, owing to the small relative surface area of the PSE. However, by altering the pH of urine locally within the pelvic recesses, the PSE has the potential of modifying the formation of renal stones within the pelvic recesses. PMID- 2330984 TI - Influence of humoral and volume factors on altered osmoregulation of normal human pregnancy. AB - These studies were designed to characterize mechanisms leading to decreased plasma osmolality (Posmol) and osmotic thresholds (T) for arginine vasopressin (AVP) release (TAVP) and thirst (Tthirst) in pregnancy. First, the influence of the pregnancy hormone, human chorionic gonadotrophin (hCG), was tested in six nonpregnant women who received hypertonic saline during the luteal phase of the menstrual cycle on two occasions (randomly allocated), once after 15,000 IU of hCG when Posmol, TAVP, and Tthirst decreased 6, 5, and 5 mosmol/kgH2O, respectively (P less than 0.01). In contrast, hCG pretreatment of males (n = 6) had no significant effect. Next, the role of decreased effective vascular volume (underfilling) was evaluated in seven women undergoing hypertonic saline infusion in the presence and absence of head-out water immersion (randomly allocated) during early and late pregnancy and postpartum. Posmol, TAVP, and Tthirst were not influenced by immersion and remained 10 mosmol/kgH2O lower in pregnancy (P less than 0.01). Central redistribution of intravascular volume consistently lowered hematocrit and rate of rise of PAVP per unit increment in Posmol (P less than 0.01). Although these data failed to support the hypothesis that the osmoregulatory change in human pregnancy is attributable to decrements in effective central volume (underfill), they do suggest that hCG may play a role. PMID- 2330985 TI - Effect of ions on binding of the thiazide-type diuretic metolazone to kidney membrane. AB - The effect of a number of ions on the binding of the thiazide-type diuretic metolazone (MTZ) to rat renal cortical membranes was studied to elucidate the mechanism of NaCl transport in the kidney distal tubule. Among the cations tested, Na+ significantly stimulated the binding up to 2.4-fold over control. The effective concentration of Na+ that produced half-maximal stimulation was 2-17 mM. Li+, K+, NH4+, Rb+, and Cs+ produced little stimulation of binding of MTZ. Several anions including Cl- inhibited binding. The inhibition of binding of MTZ by Cl- was enhanced by Na+ and Li+. Scatchard analyses revealed that 50 mM Na+ increased the affinity for binding of MTZ from a Kd = 3.56 +/- 0.15 nM to Kd = 1.32 +/- 0.11 nM. Chloride, in the presence of 50 mM Na+, competitively inhibited binding of MTZ by suppressing the affinity to Kd = 9.27 +/- 1.11 nM without changing the maximal number of binding sites (0.733 +/- 0.049 pmol/mg). A mechanism for the MTZ-sensitive NaCl transport is proposed, in which the transporter protein possesses a binding site for Na+ and a binding site for Cl-, which is also the binding site for MTZ. Na+ binds to its site and increases the affinity for Cl-/MTZ. The binding of Cl- to the transporter enables the import of Na+ and Cl- across the tubule membrane. MTZ, however, when present competes with Cl- for the binding site on the transporter and prevents the transport of Na+ and Cl-. PMID- 2330986 TI - Role of protein kinase C in proximal bicarbonate absorption and angiotensin signaling. AB - Using in vivo microperfusion in the proximal convoluted tubule (PCT) of the Munich-Wistar rat, we investigated the impact of varying protein kinase C (PKC) activity on the rate of bicarbonate reabsorption and on its regulation by angiotensin II. Activation of PKC with luminal perfusion of phorbol 12-myristate 13-acetate (PMA, 5 x 10(-7) M) caused bicarbonate absorption in the S1 PCT to increase by 25%, from 346 +/- 7 to 432 +/- 4 peq.mm-1.min-1 (P less than 0.001), without affecting intracellular cAMP level. Another PKC stimulator, dioctanoylglycerol, had the same effect. Inhibition of PKC activity with luminal perfusion of 5 x 10(-6) M sphingosine had the opposite effect, decreasing bicarbonate absorption by 45% to 190 +/- 2 peq.mm-1.min-1 (P less than 0.001). Pretreatment with PMA or with sphingosine each attenuated by approximately one third the bicarbonate absorptive response usually observed following angiotensin II administration. Similar results for the action of PKC, but of smaller magnitude, were found in the S2 PCT. In conclusion, activation of PKC increases bicarbonate and water absorption in the S1 and S2 PCT in vivo, and PKC may participate in as much as one-third of the transport stimulation induced by angiotensin II. PMID- 2330987 TI - Ionic conductive properties of rabbit proximal straight tubule basolateral membrane. AB - The ionic conductive properties of the nonperfused rabbit proximal straight tubule (S2) basolateral membrane were assessed by microelectrode techniques. The response of the basolateral membrane electrical potential difference, Vbl, to rapid changes in the peritubular bath concentration of K, HCO3, Na, and Cl were monitored with microelectrodes. The control steady-state Vbl averaged -41 mV (cell negative). An increase in peritubular bathing medium K concentration from 5 to 40 mM resulted in an instantaneous and sustained depolarization of +14.6 mV (27% of delta EK). Addition of barium (2 mM) depolarized the Vbl by +15.8 mV and abolished the Vbl response to the high-K medium. In other studies, reduction of peritubular bicarbonate at constant pH from 25 to 2.5 mM instantaneously and transiently depolarized Vbl by +15.8 mV (26% of delta EHCO3). In these same tubules reduction of peritubular Na from 126 to 2.2 mM resulted in an instantaneous and paradoxical depolarization of Vbl of +21.5 mV. Both depolarization transients resulting from reduction of Na and HCO3 were simultaneously inhibited by the addition of 4-acetamido-4'-isothiocyanostilbene 2,2'-disulfonic acid (SITS; 0.5 mM), consistent with the presence of a SITS sensitive Na-HCO3-coupled conductive pathway. In the absence of the bicarbonate buffer, reduction of Na resulted in a small sustained hyperpolarization of -5.8 mV (5% of delta ENa). Reduction of peritubular Cl from 120 to 4 mM resulted in an instantaneous and sustained depolarization of Vbl of +5.3 mV (6% of ECl) and was not affected by the addition of bumetanide (0.1 mM). It is concluded that the basolateral membrane of the nonperfused proximal straight tubule is characterized by a major barium-sensitive K conductance and a SITS-sensitive Na-coupled HCO3 conductance that carries net negative charge. These pathways are paralleled by relatively minor, but important, Na-conductive and Cl-conductive pathways. PMID- 2330989 TI - Attenuation of enhanced tubuloglomerular feedback activity in SHR by renal denervation. AB - We evaluated the effect of acute unilateral renal denervation (DNX) on the tubuloglomerular feedback (TGF) mechanism in Inactin-anesthetized hydropenic male 8- to 10-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). SHR had higher mean arterial pressure (MAP, 28%) and renal vascular resistance (RVR, 35%), whereas renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and sodium excretion were similar. DNX in SHR did not change MAP but decreased RVR (26%) and increased RBF (29%), GFR (16%), urine flow (52%), and sodium excretion (431%). DNX did not affect these in WKY. Loop of Henle perfusion with Ringer solution reduced early proximal flow rate (EPFR) in SHR more than in WKY; significantly different at a loop flow of 20 nl/min (9.8 +/- 0.7 vs. 6.5 +/- 0.7 nl/min). DNX in SHR increased the nonperfused EPFR from 25.6 +/- 1.1 to 31.7 +/- 1.3 nl/min and reduced TGF responses during perfusion at both 20 nl/min (9.8 +/- 0.7 vs. 4.4 +/- 0.7 nl/min) and 40 nl/min (14.2 +/- 1.1 vs. 10.4 +/- 0.7 nl/min). TGF sensitivity was attenuated by DNX, as indicated by reduced maximum reactivity (-0.89 +/- 0.14 to -0.36 +/- 0.07) and increased turning point (16.5 +/- 0.9 to 25.2 +/- 2.9 nl/min). TGF responses in WKY were not influenced by DNX. Sham denervation did not alter renal hemodynamics and TGF. These results indicate that renal nerves exert a tonic influence on the renal vasculature and the TGF system in SHR but not in WKY. Enhanced TGF responsiveness may be involved in volume retention and in the maintenance of hypertension in SHR. PMID- 2330988 TI - Cell swelling activates basolateral membrane Cl and K conductances in rabbit proximal tubule. AB - The ionic basis of volume regulation was assessed in the nonperfused rabbit proximal tubule (S2 segment) by use of simultaneous measurements of tubule volume via video-optical imaging techniques and basolateral membrane voltage (Vbl) and relative ionic conductance via conventional microelectrodes. Both cell volume (9.9 +/- 0.70 nl/cm tubule length) and Vbl (-42.8 +/- 3.6 mV) remained stable in the control isotonic Ringer solution (290 mosmol/kg). When the osmolality of the bathing medium was reduced to 150 mosmol/kg, tubules swelled 72% above base line within 1 min and subsequently regulated over the course of the next 4-6 min to a steady state 20 +/- 3% above the initial base-line volume. Cell swelling was accompanied by a transient hyperpolarization of Vbl of -14.3 +/- 2.0 mV (HCO3 containing Ringer) and -10.0 +/- 0.7 mV (HCO3-free Ringer). Although the hyperpolarization was not inhibited by barium in the presence of bicarbonate buffer, addition of 2 mM Ba to a bicarbonate-free Ringer depolarized Vbl by +22 mV and abolished both the relative potassium conductance and the hyperpolarization accompanying cell swelling (delta Vbl = -4.6 +/- 0.6 mV). Furthermore, the relative conductance of K at the basolateral membrane increased from 0.16 in the isotonic control medium to 0.34 at the peak of cell swelling. Because the hyperpolarization of Vbl ensued after cells had swollen approximately 10% above base line, a modest threshold volume and time delay may be involved in triggering the volume-dependent activation of the K conductance. In parallel studies, the change in Vbl on a rapid step-change in bath Cl (49 to 4.9 mM) averaged 5.3 +/- 1.0 mV in the isotonic solution and increased to +11.3 +/- 2.1 (P less than or equal to 0.05) at the peak of cell swelling. This represented an increase in the relative Cl conductance of 0.08 to 0.20, which could only be attributed to an absolute increase in the basolateral membrane Cl conductance and not to a reduction in the other major basolateral membrane conductances. It is concluded that cell swelling results in an increase in both Cl and K conductance, which may underlie subsequent cell volume regulation. PMID- 2330990 TI - Effect of specific amino acid groups on renal hemodynamics in humans. AB - The effect of specific amino acid groups on renal hemodynamics was examined in seven healthy young volunteers. Each subject received a 3-h intravenous infusion according to one of the following protocols: study 1, gluconeogenic amino acids (Arg, Gly, Pro, Cys, Met, Ser); study 2, alanine alone; study 3, branched-chain amino acids (BCAA, Leu, Ile, Val); or study 4, 0.9% saline. The rise (40-60% above base line) in total plasma amino acid concentration was similar in studies 1-3; no change was observed in study 4. During study 1, glomerular filtration rate (GFR) rose by 16% (from 98 +/- 6 to 114 +/- 8 ml.1.73 m-2.min-1, P less than 0.01), and renal plasma flow (RPF) rose by 28% (from 496 +/- 47 to 638 +/- 70 ml.1.73 m-2.min-1, P less than 0.01). After alanine (study 2) and BCAA (study 3) infusion, there was a slight, although not significant, rise in GFR and RPF; during saline infusion (study 4), GFR and RPF remained unchanged. Plasma insulin and growth hormone did not change significantly in any study protocol. Plasma glucagon rose significantly by 30% in study 1 (from 117 +/- 10 to 151 +/- 13 pg/ml, P less than 0.05) but did not change in studies 2-4. In summary, infusion of mixed gluconeogenic amino acids increases both GFR and RPF, and neither alanine nor BCAA infusion caused a consistent alteration in renal hemodynamics. PMID- 2330991 TI - Mechanisms of reduced reperfusion injury by low Ca2+ and/or high K+. AB - Mechanisms of the protective effects of low Ca2+ (0.15 mM) and/or high K+ (20 mM) concentrations in the buffer on reperfusion injury were investigated. Intracellular Na+ (Nai+) increased fourfold during 25 min of ischemia. When hearts were reperfused with the standard buffer (1.25 mM Ca2+, 5.9 mM K+), Nai+ increased further during the 1st 2 min (5-fold) and then declined by 30% at 10 min of reperfusion. Ca2+ uptake increased 6- and 12-fold at 10 and 30 min of reperfusion, respectively. Function, which was assessed as the product of developed pressure and heart rate, recovered to 45% of the preischemic value and end-diastolic pressure was elevated (EDP: 31 mmHg). Reperfusion for 10 min with low Ca2+ buffer abolished the increase in Ca2+ uptake during this period, but it increased 10-fold when the perfusate was switched back to the standard buffer. Accelerated Ca2+ influx at this time was probably through Na(+)-Ca2+ exchange because Nai+ did not decline during low Ca2+ reperfusion. Elevation of EDP was suppressed (12 mmHg), but development of pressure did not increase. Reperfusion for 10 min with high K+ buffer accelerated the decline in Nai+ by 70% and reduced the increase in Ca2+ uptake (8-fold). Recovery of function improved (67%, EDP: 18 mmHg). Further improvement in function (78%, EDP: 10 mmHg) was obtained along with less Ca2+ uptake (7-fold) when low Ca2+ and high K+ were combined. Recovery of energy metabolites at 10 and 30 min of reperfusion was not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330992 TI - Combined effects of autoregulation and vasoconstrictors on hindquarters vascular resistance. AB - Relative contributions of local autoregulatory tone and vasoconstrictor tone to skeletal muscle vascular resistance were studied in anesthetized rats during hypertension produced by vasoconstrictor infusion. Rats were instrumented with a Doppler flow probe on the sacral aorta (SA) to measure blood flow and to allow calculation of vascular resistance. An occluder was placed on the SA and used to produce stepwise reductions in local perfusion pressure. Pressure-flow curves for the hindquarters were obtained in the absence and presence of elevated mean arterial pressure (MAP) produced by infusion of angiotensin II (ANG II; 50-1,247 ng.kg-1.min-1) or phenylephrine (PE; 2.5-12.4 micrograms.kg-1.min-1). Both ANG II and PE infusion increased MAP. For example, MAP was increased by ANG II from 91 to 134 mmHg and by PE from 89 to 156 mmHg. In addition, infusions of ANG II and PE produced dose-dependent rightward shifts in the hindquarters pressure-flow relationship. To examine the effect of pressure on the dose-response relationships of ANG II or PE, local perfusion pressure was adjusted to remain constant at various pressure levels that were independent of MAP during drug infusions. This produced a series of distinct dose-response curves with each curve defined by a different pressure level and with each characterized by a different maximum change in vascular resistance. If local perfusion pressure was not held constant but was permitted to increase with MAP, a compound dose response curve was obtained in which the combined effects of the change in local pressure (i.e., autoregulation) and vasoconstrictor dose on vascular resistance could be discerned. These data demonstrate that hindquarters blood flow autoregulation continues to occur in the presence of vasoconstrictors. Consequently, autoregulatory mechanisms may be stimulated by any increase in MAP whether associated with systemic vasoconstrictor infusion or activation of neurohumoral pressor systems. The result is an amplified rise in local vascular resistance. PMID- 2330993 TI - Effect of acute hypoxemia on brain blood flow and oxygen metabolism in immature fetal sheep. AB - Studies of cerebral blood flow and oxygen metabolism during acute hypoxic hypoxia in fetal sheep have been confined to late gestation, a time when brain development in this species is largely complete. There is no systematic study of cerebral vascular responses to acute hypoxic hypoxia in immature fetal sheep or, indeed, in immature brains of any species. We studied 13 fetal sheep in utero at 93 +/- 1 days gestation (term = 145-150 days), 48 h after intravascular catheters were placed into the superior sagittal sinus, axillary arteries, and inferior vena cava. We measured brain blood flow by the microsphere method. Cerebral oxygen consumption was calculated with the use of blood flow to the cerebral hemispheres (cerebrum, diencephalon, mesencephalon) and arterial and sagittal sinus values for oxygen content. Fractional oxygen extraction was calculated as the ratio between oxygen consumption and oxygen transport. We altered fetal oxygenation by changing the mother's inspired oxygen concentration. As in the near-term fetus, acute hypoxic hypoxia resulted in increased blood flow to cerebral hemispheres, cerebellum, and pons-medulla; furthermore, the increase in blood flow was sufficient to sustain cerebral oxygen consumption. However, in contrast to near-term fetuses, the increase in blood flow to the cerebral hemispheres was not sufficient to maintain convective oxygen transport. Cerebral oxygen consumption was therefore sustained in part by an increase in fractional extraction. Blunted hypoxic vasodilation in immature fetuses might reflect either immature regulatory mechanisms or an inability of cerebral vessels to respond to the usual stimuli. It is also possible that hypoxic vasodilation was blunted by reflex stimulation of the sympathetic nervous system. PMID- 2330994 TI - Adenosine-induced changes in atrial action potential: contribution of Ca and K currents. AB - In this study, we examined the relative contribution of the increase in acetylcholine-regulated potassium current (IK ACh) and decrease in calcium current (ICa) to the adenosine (Ado)-induced shortening of action potential duration (APD). In isolated guinea pig atrial myocytes, membrane potentials and currents were measured by the whole cell patch-clamp technique. ICa and IK ACh were individualized by blocking the K currents with Cs+ and ICa with Cd2+. The effects of Ado on membrane potential and currents were concentration dependent. Ado (10 microM) shortened APD at 0 mV and at 90% of repolarization (APD0,90) to 7 +/- 1 and 26 +/- 6 ms from control values of 23 +/- 3 and 89 +/- 6 ms, respectively. Concomitant with the changes in APD, Ado decreased ICa from -9.2 +/ 1.3 to -6.8 +/- 10 microA/microF (26% decrease) but increased IK ACh from +3.5 +/- 0.5 to +7.8 +/- 0.8 microA/microF (123% increase). When rundown of ICa was taken into account, the maximum decrease in ICa caused by Ado was 12%. The effect of Ado on ICa and IK ACh was not altered by treatment of the cells with either Cs+ or Cd2+. The shortening of ADP0,90 strongly correlated with the increase in IK ACh but minimally with the decrease in ICa. A 22% reduction in ICa caused by lowering extracellular Ca2+ concentration ([Ca2+]o) from 3.6 to 1.8 mM was associated with an 11 and 14% shortening of APD0 and APD90, respectively. In the same myocytes an 18% decrease in ICa by 10 microM Ado reduced APD0 and APD90 by 58 and 61%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330995 TI - External pressure of undisturbed left ventricle. AB - We evaluated the contribution of the thorax and the undisturbed pericardium to the external pressure of the euvolemic left ventricle in thirteen anesthetized dogs. Left ventricular (LV) end-diastolic pressure (EDP) in the euvolemic state was 7 +/- 2 mmHg initially and increased to 10 +/- 2 mmHg after the chest and pericardium were opened. LV end-diastolic volume (conductance catheter) was 43 +/ 20 ml initially and did not change after the chest or the pericardium was opened. Intrathoracic (PIT) and pericardial (PPER) pressures were calculated as the difference in LV chamber pressure before and after opening these spaces. Thus for the LV, PIT was -3 +/- 1 mmHg, and PPER was 0 +/- 2 mmHg. Isovolumic relaxation, early diastolic filling, and total diastolic filling were not significantly altered after the chest or pericardium was opened. Thus under euvolemic conditions in this model pericardial pressure is negligible, and the external pressure of the undisturbed left ventricle is negative and equal to intrathoracic pressure. PMID- 2330996 TI - Activation in frog atrial trabeculae: dependence on temperature and length. AB - Isolated frog atrial trabeculae were activated using the method of Na+ withdrawal to induce contractures of relatively steady tension. External Na+ concentration [( Na+]o) during contractures was varied between 0.25 and 45 mM. Isometric contracture tension was measured at cold (4 degrees C) and warm (20 degrees C) temperatures. In addition, rapid temperature jumps (complete in approximately 400 ms) were imposed during cold contractures, resulting in tension transients that consisted of an initial increase in tension followed by a decrease, the latter phase being greater at small and moderate reductions in [Na+]o. Peak contracture tension varied with relative muscle length. The trabeculae became more sensitive with stretch to Na+ withdrawal at 20 degrees C and generated relatively greater tensions at a given [Na+]o. The initial tension increase after a temperature jump was directly proportional to the peak contracture tension immediately preceding the increase in temperature and was therefore interpreted as reflecting an effect of the higher temperature on the attached force-generating cross bridges. The effects of cold and warm steady temperatures and temperature jumps during isometric twitches were also studied. Peak twitch tension varied inversely with temperature (stimulus frequency = 0.2 Hz). In contrast, temperature jumps imposed during the rising phase of twitches at a steady cold temperature (approximately 4 degrees C) resulted in a large initial increase in tension followed by relaxation at a rate that was characteristic of the elevated temperature. The results suggest that, at the warmer temperature (approximately 20 degrees C), activation (i.e., number of attached cross bridges) of the myocardium is significantly less than maximal during the twitch response. The dependence of the tension vs. [Na+]o curves and the tension transients resulting from the temperature jumps on relative muscle length provide evidence for a length dependency of contractile activation in intact atrial trabeculae under conditions of steady-state tension development. PMID- 2330997 TI - Short-term systemic autoregulation. AB - We studied total systemic autoregulation in closed-chest, chloralose-anesthetized dogs. Cardiac out-put (previously implanted electromagnetic flow probe on ascending aorta) and aortic pressure were varied by reducing venous return using a balloon catheter in the vena cava. Compensatory action of the baroreflex was prevented by bilateral vagotomy and isolation of both carotid sinuses. To avoid high vessel tone carotid sinus pressure was set at the original baseline value using a pressurized blood reservoir. With each balloon inflation aortic flow and aortic pressure decreased and stabilized in about 1 min. Pressure and flow were allowed to return to base-line values after each balloon inflation in an attempt to minimize the activation of slower regulatory mechanisms. The steady-state pressure-flow relations could be fitted with a sigmoidal curve. The mean quality (0 less than Q less than 1) of autoregulation in eight dogs was 0.41 +/- 0.08 (SD). Autoregulation was found in the pressure range from 42 to 140 mmHg. The early appearance of total systemic autoregulation suggests that, in the intact animal, it may counteract baroreflex control. PMID- 2330998 TI - Microvascular occlusions promote coronary collateral growth. AB - The objective of this study was to examine whether myocardial ischemia without alterations in pressure gradients between large epicardial coronary arteries was a sufficient stimulus to produce coronary collateral growth and development. To accomplish this aim, we partially embolized the circumflex coronary perfusion territory with 25-microns diameter microspheres to produce multiple microvascular occlusions, sufficient to abolish or greatly attenuate coronary vasodilator reserve. The embolization procedure was performed in two groups of dogs during aseptic surgery. After the dogs recovered for 1-3 wk (short-term embolization) or 6-8 wk (long-term embolization), indexes of vascular growth were compared with a group of control animals in which all operative procedures were performed, except embolization. Retrograde blood flow, an index of collateral blood flow and coronary vascular resistance, was determined in an isolated beating empty heart preparation during coronary vasodilation with adenosine. Circumflex retrograde blood flow from the left anterior descending artery was increased from 0.09 ml.min-1.g-1 (sham) to 0.21 and 0.17 ml.min-1.g-1 in the short-term and long-term groups, respectively (P less than 0.05). Collateral blood flow from the septal artery was also increased from 0.03 ml.min-1.g-1 (sham) to 0.08 ml.min-1.g-1 (P less than 0.05) in the short-term group. Collateral contribution from the right coronary artery was not significantly altered in either group of embolization animals. The contributions of epicardial and intramyocardial collaterals to the total retrograde flow were also determined and were found to be different among the three experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2330999 TI - Cardiac electrical responses to vagal stimulation of fibers to discrete cardiac regions. AB - We stimulated regional intracardiac parasympathetic nerve fibers to the atrioventricular (AV) nodal area (AVP stimuli) or to the sinoatrial (SA) nodal area (SAP stimuli) in autonomically decentralized, anesthetized dogs. AVP stimuli increased the AV interval (AV conduction time); the magnitude of the response depended directly on the stimulation frequency. AVP stimuli did not alter the atrial interval (heart period) in spontaneously beating hearts. The magnitude of the negative dromotropic response increased when the atrial interval was shortened. SAP stimuli increased the atrial interval, and the magnitude of the response depended directly on the stimulation frequency. SAP stimuli evoked little or no change in the AV interval in the unpaced heart. When the atrium was paced, SAP stimuli did not change the AV interval in about half of the preparations, and there was a small but significant change in the remaining preparations. The negative dromotropic or chronotropic response to AVP or SAP stimuli was potentiated by physostigmine and blocked by atropine. These results suggest that 1) AVP stimuli induce a selective negative dromotropic response, and 2) this negative dromotropic effect is secondarily affected by heart period, by the pacemaking site, and by atrial activation patterns, but it does not affect the sinus cycle length in the dog heart. PMID- 2331000 TI - Regional circulatory responses to intestinal work in developing swine. AB - Circulatory effects of intraduodenal feeding with 2 and 5% glucose were studied in 29 fasted swine (1 day to 1 mo old) anesthetized with pentobarbital. Recordings included aortic and intestinal venous pressures and intestinal, renal, and femoral blood flows. Calculations included vascular resistances, arterial and intestinal venous O2 contents, and intestinal O2 consumption. Observations were made before and at 15 and 30 min after a feeding and at end of experiments. Blood flow autoregulation was evaluated before and after feedings. Glucose induced increases in intestinal O2 consumption and blood flow at all ages, but intestinal blood flow autoregulation was enhanced only in 2 wk olds. Blood flow was redistributed to the working gut from the hindlimb, but not the kidney, at all ages. Renal blood flow autoregulation was sustained in 2-wk-old and 1-mo-old animals and became significant in 1 wk olds during intestinal hyperemia. We concluded that basic mechanisms governing blood flow redistribution from hindlimb to working gut are available at birth in swine and that maintenance of renal blood flow depends only partly on autoregulatory capability. PMID- 2331001 TI - Hemodynamic changes associated with anaphylaxis in parasite-sensitized rats. AB - Thirty days after infection with the parasite Nippostrongylus brasiliensis, microcirculatory changes associated with worm allergen-induced anaphylactic shock in pentobarbital-anesthetized rats were studied. Allergen challenge decreased heart rate, mean arterial blood pressure, and cardiac output (CO) for 60 min, although CO increased markedly by 240 min. Blood flow (ml.min-1.g wet tissue-1) was reduced to most tissues, with the exception of the kidneys, hepatic arterial, heart, and brain, for 60 min. Depressed flow to the adrenals and enhanced flow to the kidneys, trachea, stomach, and mesentery were observed at 240 min. The percent distribution of cardiac output per gram wet tissue (%CO/g) increased initially to the kidneys, heart, liver, and cervical spinal cord, decreased to the spleen and cecum, and remained unchanged to other gastrointestinal tissues. The %CO/g to most tissues returned to normal by 60 min but decreased to the adrenals at 240 min. The intestine is an important organ affected by anaphylaxis in the rat, and the liver may participate in alleviating anaphylaxis. PMID- 2331002 TI - Oxidative and glycolytic ATP formation of rabbit papillary muscle in oxygen and nitrogen. AB - Contraction-related O2 consumption of rabbit papillary muscles was determined at 20 degrees C by measuring change in saline PO2 during and after trains of 120 twitches at 0.125-1 Hz in a microrespirometer. Although anoxic cores occurred at twitch frequencies greater than 0.2 Hz, no lactate was found in saline after twitch train. To measure lactate accumulation in muscle, fully oxygenated muscles were frozen at rest and during steady-state twitches at 0.2 Hz. We also measured nucleotides and creatine (Cr) compounds. There were no differences in lactate, ATP, and phosphocreatine (PCr) content between the resting and active muscles. When a P-to-O2 ratio of 6.3 is assumed, aerobic ATP formation was compared with glycolytic ATP formation during anoxia at a stimulus frequency of 0.2 Hz. The latter value was obtained by freezing muscles between 6 and 25 min after changing from O2- to N2-saturated saline. Withdrawal of O2 caused the ratio of PCr to total Cr to fall in less than 6 min from 0.77 to 0.23, while ATP remained at approximately 15 mumol/g dry wt. Force fell initially within 4 min to approximately 70% of control value, decreasing thereafter more slowly to approximately 40% at 20 min. From the relationship between amount of lactate formed and duration of anoxia, rate of anaerobic ATP formation was calculated assuming a P-to-lactate ratio of 1. We found that despite continuing contractile activity, anaerobic ATP formation was less than that required by a fully oxygenated resting muscle and was about the same magnitude as the estimated ATP hydrolysis for the contractions in N2. We conclude that in fully oxygenated rabbit papillary muscles no net lactate is produced during stimulation and that in anoxia anaerobic glycolytic capacity may not provide sufficient ATP for processes other than the uptake of Ca by the sarcoplasmic reticulum and cross bridge cycling. PMID- 2331003 TI - Atrial tachycardia causes hydrops in fetal lambs. AB - The purpose of this project was to study mechanisms responsible for edema formation in fetuses with hydrops. We produced hydrops fetalis in 28 fetal sheep [gestational age of 125 +/- 5 days (mean +/- SD)] by pacing their atria at 300 320 beats/min for 68 +/- 40 (SD) h. All fetuses developed peripheral edema and ascites [volume of ascitic fluid was 134 +/- 75 (SD) ml; total protein concentration was 3.10 +/- 0.6 (SD) g/dl, and total albumin concentration was 1.68 +/- 0.3 (SD) g/dl]. Pacing did not affect aortic pressure but increased venous pressure from 4 +/- 1 to 8 +/- 1 (SE) Torr. Pacing did not affect pH, arterial partial pressure of O2 (PaO2), or Na+ but increased PaCO2 from 53 +/- 1 to 55 +/- 1 (SE) Torr and K+ from 3.9 +/- 0.1 to 4.3 +/- 0.1 (SE) meq/l. Hematocrit increased from 29 +/- 1 to 32 +/- 1 (SE)% acutely with pacing but returned to base line by the last day of the experiment. Plasma protein concentration decreased slightly from 3.7 +/- 0.1 to 3.5 +/- 0.1 (SE) g/dl by the last day of the experiment; plasma albumin concentration did not change. Plasma volume decreased acutely from 271 +/- 19 to 238 +/- 16 (SE) ml and then remained decreased throughout the experiment. Red blood cell mass and the turnover time for albumin were not affected by pacing. We found no consistent relationship between edema formation and changes in arterial blood gas tensions, plasma protein concentrations, or the turnover time for albumin.2 PMID- 2331004 TI - Effect of pulmonary venous pressure elevation on vascular resistance and compliance. AB - The effect of pulmonary venous pressure elevation on the longitudinal distribution of resistance and compliance in the canine pulmonary circulation was determined at control vascular tone and after vascular tone was increased with histamine. The arterial, venous, and double-occlusion techniques were used in isolated dog lungs blood perfused at constant flow. The large and small blood vessel resistances and compliances were studied under both vascular tone conditions when pulmonary venous pressure was elevated above isogravimetric venous pressure conditions in successive 5 cmH2O increments up to 30 cmH2O. The results of this study indicate that pulmonary venous pressure elevations to 20 cmH2O above isogravimetric venous pressure significantly decrease total vascular resistance by reducing both the small and large vein resistances, an effect which is more pronounced in the histamine-treated lungs. Also, under control vascular tone, both the middle compartment compliance and total compliance were greatly decreased over this pressure range. Histamine treatment significantly reduced both the large vessel and middle compartment compliances before and during low venous pressure elevation. When venous pressure was then raised to at least 25 cmH2O above control outflow pressure with histamine present, the middle compartment compliance was again significantly decreased. PMID- 2331005 TI - Myogenic autoregulation of flow may be inversely related to endothelium-derived relaxing factor activity. AB - The influence of basal endothelium-derived relaxing factor (EDRF) activity on autoregulation was studied under conditions of controlled-flow and controlled pressure perfusion in the isolated rabbit ear, a weakly autoregulating vascular bed. Hemoglobin and NG-monomethyl-L-arginine were used to inhibit EDRF activity, and in some experiments resting tone was increased by serotonin. The diameters of five generations of resistance arteries (ranging from 70 to 1,000 microns in size) were measured at different flow rates by X-ray microangiography. Diameter flow (D-Q) relationships were correlated with pressure-flow (P-Q) and conductance flow (G-Q) relationships. In the presence of EDRF activity no autoregulation was observed, P-Q relationships being linear and G-Q and D-Q relationships common both to controlled-flow and to controlled-pressure modes of perfusion. After inhibition of EDRF activity in constricted preparations, P-Q relationships became sigmoidal in shape in controlled-pressure perfusion mode, reflecting a range of perfusion pressures/flow rates over which they were able to "autoregulate" flow. Over this autoregulatory range the corresponding G-Q and D-Q relationships exhibited regions of negative slope. Autoregulation was not observed in controlled-flow perfusion mode even in the absence of EDRF activity. The findings imply that flow- or pressure-dependent constriction can mediate autoregulation in controlled-pressure mode when not overridden by basal EDRF activity, as normally appears to be the case in these preparations. Differences in autoregulation in different organs may be inversely related to EDRF activity, which is known to differ between vascular beds. PMID- 2331006 TI - Measurement of left ventricular mass in rats using electrocardiogram-gated magnetic resonance imaging. AB - To evaluate the ability of electrocardiogram (ECG)-gated magnetic resonance (MR) imaging to assess in vivo left ventricular (LV) mass in the rat, we studied 20 healthy adult Sprague-Dawley and Fischer 344 rats and 8 additional rats that underwent scanning after induction of volume overload by aortic leaflet disruption. ECG-gated spin-echo pulse sequences were used to acquire a series of 1-mm thick modified short-axis images of the left ventricle. The area enclosed by the endocardial and epicardial borders of the left ventricle was multiplied by the interslice distance and specific gravity of myocardium to obtain calculated slice mass. Total LV mass was obtained by summing the individual slices. The calculated value for LV mass was then compared with the LV mass as determined at postmortem examination. Linear regression analysis showed an excellent correlation of MR-estimated mass (x) with autopsy-measured LV mass (y) (y = 0.90x + 65, r = 0.98). For this method intraobserved and interobserver slice correlations were 0.97 and 0.96, respectively. There was no significant difference in LV mass as determined from a series of diastolic vs. systolic images in a subset of six animals. Over a mean of 6.5 wk of observation, LV mass increased by 40% in the animals subjected to aortic leaflet disruption. These results demonstrate that MR imaging is highly accurate for the non-invasive in vivo assessment of LV mass in the adult rat. PMID- 2331007 TI - Effect of lactic acidosis on canine hemodynamics and left ventricular function. AB - Hypoperfusion states cause lactic acidosis, and the acidemia further reduces the inadequate cardiac output. Conceivably, the adverse effect of lactic acidemia on cardiac output is due to depressed contractility demonstrated in isolated myocardium. Alternatively, factors governing venous return cause a relative hypovolemic state and/or acidemic pulmonary vasoconstriction-induced right ventricular dysfunction. We reasoned that examination of left ventricular pressure-volume relationships at end systole and end diastole would determine which of these potential mechanisms accounted for reduced cardiac output during progressive lactic acidosis in anesthetized, mechanically ventilated dogs. Left ventricular (LV) volume was estimated from two pairs of epicardial ultrasonic crystals placed in the anterior-posterior and longitudinal planes, and LV pressure was obtained rom a catheter-tipped transducer. During progressive acidemia induced by a continuous intravenous infusion of 0.5 N lactic acid, cardiac output, stroke volume, and mean systemic arterial pressure fell significantly while mean pulmonary artery pressure and right atrial pressure increased significantly. These variables did not change with time in control (no acid infusion) dogs. Lactic acidemia caused a 40% reduction in stroke volume, which could be attributed to depressed LV contractility, characterized by a decrease in maximum dP/dt as well as a fall in slope (Emax) with no change in volume intercept (Vo) of the left ventricular pressure-volume relationship at end systole. Neither the measured left ventricular end-diastolic pressure nor the estimated left ventricular end-diastolic volume (LVEDV) decreased with acidemia, suggesting that the reduced venous return did not result from relative hypovolemia. However, acidemic pulmonary hypertension may have interfered with the expected response to myocardial depression, which is an increase in LVEDV. PMID- 2331008 TI - Calcium-sensitive delayed rectifier potassium current in guinea pig ventricular cells. AB - The calcium sensitivity of the delayed rectifier K+ current (IK) was investigated in guinea pig single ventricular cells using the whole cell configuration of the patch-clamp technique with a cell dialysis method. The concentration-response curve of IK for intracellular Ca2+ indicated that IK started to increase at intracellular Ca2+ concentration [Ca2+]i of 10(-8) M (pCa 8) and it increased threefold at pCa 7. At lower [Ca2+]i than pCa 9, IK remained unchanged. A shift of the activation curve of IK by the elevation of [Ca2+]i was not observed. Although [Ca2+]i had little effect on time constants of the activation and deactivation of IK, it predominantly increased the amplitudes of the fast components in the activation process and the slow component in the deactivation process. In the ensemble noise analysis, the elevation of [Ca2+]i increased the number and open probability of functional IK channels but not the unit amplitude of IK channel. These results suggest that the elevation of [Ca2+]i enhances IK, probably by increasing the number and open probability of functional IK channels. Ca2(+)-sensitive IK in cardiac cells is a class of current different from Ca2(+) activated K+ current in other tissue because the activation curve of Ca2(+) sensitive IK was not shifted by the [Ca2+]i elevation, and the single channel conductance of IK was smaller than the one of Ca2(+)-activated K+ current. PMID- 2331009 TI - Determination of red blood cell oxygenation in vivo by dual video densitometric image analysis. AB - We have developed a new video microspectrophotometric system for the in vivo determination of oxygen saturation in red blood cells in striated muscle capillaries. This method allows one to quantify changes in the oxygenation of small groups of red blood cells as they traverse the capillary. Simultaneous images of a single microscopic field are recorded using two silicon-intensified target cameras and high-resolution video recorders. One image is recorded at an oxygen-dependent wave-length (431 nm) and the other at an isosbestic wavelength (420 nm). Light intensities from 10 adjacent pixels aligned along the axis of the capillary from identical 10-s segments of the video-tapes are digitized once per frame. Both sets of data are redisplayed simultaneously as two-dimensional images (10 pixels high x 300 frames wide) using a graphics system. These images show alternating bright and dark bands corresponding to plasma gaps and red blood cells. Light intensities in the presence and absence of red blood cells are determined by positioning a window over the appropriate region of the graphics image. Optical densities of single red blood cells at the two wavelengths, OD431 and OD420, are computed as is their ratio (OD431/OD420), which is linearly related to oxygen saturation. In vivo calibration studies in capillaries of the hamster retractor muscle indicate that the error in measuring oxygen saturation with this technique is approximately 2.7% saturation for a group of 10 cells. PMID- 2331010 TI - Fabrication, evaluation, and use of extracellular K+ and H+ ion-selective electrodes. AB - Ion-selective mini-electrodes have been widely employed to measure extracellular K+ and H+ during myocardial ischemia. However, the recent availability of this technology has not been accompanied by uniform fabrication, amplification, and calibration standards. In their fabrication, the chloride tips of Teflon-coated silver wires should be covered with a cellulose acetate-titanium dioxide sponge followed by a polyvinyl chloride (PVC)-valinomycin (K+) or PVC-tridodecylamine (H+) ion-selective membrane. Critical analysis of the nonworking electrodes using scanning electron micrographs has revealed membrane holes, membrane and sponge contamination, Teflon plaque, poor membrane-sponge-Teflon adhesion, and improperly applied or torn membrane. We have also found that signal amplification must have variable-gain filtration (0-1 Hz) with 0.5-pA input offset current and 10(12)-omega input resistance. Furthermore, in vitro calibration in 3 and 10 mM KCl (K+) or pH 8 and 6 buffer (H+) should produce a Nernstian slope +/- 5 or 10%, respectively, at 26 degrees C with a response time less than or equal to 50 ms, resistance greater than or equal to 10(12) omega, and drifts less than or equal to 1 mV/h. In vivo performance and calibration criteria (delineated for K+ only) include 1) transient response to bolus injections of KCl (0.12 mM/kg body wt) yielding peak amplitude changes of 2.5-3.0 mM, response times less than or equal to 10 s, and washout time constants less than or equal to 3 min, and 2) in vivo calibration to artificial independently confirmed systemic [K+] producing a Nernstian slope +/- 15% at 38 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331011 TI - A new method of sampling blood for measurement of plasma adenosine. AB - The half-life of adenosine in human blood is 1-2 s at 37 degrees C. To measure plasma adenosine concentration accurately, it is necessary to inhibit adenosine metabolism during transit of blood through the sampling catheter. We have tested a double-lumen catheter and a solution of compounds that inhibit adenosine metabolism (stop solution) for this purpose. Stop solution and radiolabeled adenosine were delivered via an inner lumen, mixed with blood at the catheter tip, and withdrawn to a collection syringe in an outer lumen. Extracellular recovery of label was 89 +/- 5% and proportional to the quantity of label added to blood. In contrast, when blood and radiolabel were mixed with stop solution in the collecting syringe only after passage through the catheter, recovery of radiolabel was 7 +/- 3%. The importance of inhibiting pathways of adenosine formation and degradation or uptake during transit of blood through the catheter was demonstrated. The results suggest that a double-lumen catheter and stop solution are both necessary and suitable for collection of human blood to determine the concentration of plasma adenosine. PMID- 2331012 TI - Arterioles supply oxygen to capillaries by diffusion as well as by convection. AB - In the early part of this century, August Krogh proposed a model of oxygen transport in capillaries that assumes that all oxygen is delivered to the capillaries by convection from small terminal arterioles and lost from these capillaries by diffusion. This model and its consequences have been used extensively to interpret whole organ oxygen transport data in terms of diffusion between capillaries and tissues and to relate changes in microvascular hemodynamics to alterations in oxygen transport. We evaluated the appropriateness of such extrapolation by measuring oxygen saturation at discrete locations along the lengths of individual capillaries in the hamster cheek pouch retractor muscle. Our results indicate that the amount of oxygen lost from individual capillaries can be markedly affected by the presence of larger microvessels that frequently cross the capillary path. These larger vessels act either as a diffusive supply of oxygen for the red blood cells within the capillary or as an additional sink for the oxygen depending on the direction of the oxygen tension gradient. This transfer of oxygen between larger microvessels and capillaries attenuates the importance of capillary hemodynamics in oxygen exchange. Therefore, conclusions about local oxygen exchange that utilize only hemodynamic data from whole organ or microvascular experiments and the Krogh model will generally be invalid and should be viewed with caution. PMID- 2331013 TI - Cocaine inhibits baroreflex control of blood pressure by actions at arterial baroreceptors. AB - Blood pressure and heart rate often increase during cocaine intoxication, but the mechanisms of these cardiovascular responses are poorly understood. The most often suggested theories are central nervous system mechanisms involving the blockade of neuronal transmitter uptake. Cocaine also has potent local anesthetic properties, and in this study we tested the possible role of peripheral actions of cocaine at baroreceptor afferents. Single fiber baroreceptors were recorded using an in vitro preparation of the rat aortic arch. Diameter, pressure, and baroreceptor discharge were recorded. Cocaine perfused through the lumen of the aortic arch at a suprathreshold pressure reduced baroreceptor discharge within 90 s of entering the lumen of the aorta. Slow ramps of pressure elicited complete pressure- and diameter-discharge curves every 5 min. Beginning at about 1 microM, cocaine inhibited baroreceptor function; threshold increased, the maximum discharge decreased, and at 100 microM cocaine, all discharge ceased. The vasodilator nitroprusside or the alpha 1-adrenoreceptor antagonist prazosin did not affect baroreceptor responses to cocaine. In in vivo tests in rabbits, cocaine that perfused through a vascularly isolated carotid sinus reduced the slope of the baroreflex relationship between carotid sinus pressure and systemic mean arterial pressure. Significant depression of baroreceptor function was found at concentrations similar to the plasma cocaine levels measured in clinical studies. The local anesthetic properties of cocaine may be involved in baroreceptor effects. Our studies suggest a possible contributing role of a new site of action of cocaine outside the central nervous system. Compromise of baroreceptor reflexes could facilitate the development of serious cardiovascular complications associated with cocaine abuse. PMID- 2331014 TI - Nitric oxide modulates epicardial coronary basal vasomotor tone in awake dogs. AB - This study evaluates the role of endogenous nitric oxide in the modulation of basal coronary vasomotor tone by studying the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation from L-arginine, on resting epicardial coronary diameter and coronary flow. L-NMMA (5 mg/kg) was infused in seven awake dogs chronically instrumented with coronary dimension crystals for measurement of epicardial coronary diameter, and Doppler flow probes for quantitation of phasic coronary flow (vasomotion of distal regulatory resistance coronary vessels). Epicardial coronary diameter decreased 5.5% from 3.47 +/- 0.17 to 3.28 +/- 0.15 mm (mean +/- SE). The diameter change was gradual, reaching a maximum at 13 +/- 2 min after infusion, and persistent, lasting greater than 90 min. Phasic coronary flow did not change. Mean aortic pressure significantly increased from 99 +/- 3 to 111 +/- 3 mmHg and heart rate decreased from 56 +/- 4 to 46 +/- 3 beats/min. Left ventricular end-diastolic pressure and contractility were not significantly altered. L-Arginine (66 mg/kg) but not D-arginine reversed all hemodynamic parameters. These data support an important role of nitric oxide in modulating basal epicardial coronary vasomotor tone and systemic vascular resistance. PMID- 2331015 TI - Area postrema and differential reflex effects of vasopressin and phenylephrine in rats. AB - In normal rats, baroreflex inhibitions of heart rate (HR) and splanchnic but not lumbar sympathetic neural activity (SNA) are greater when mean arterial pressure (MAP) is increased by intravenous infusion of arginine vasopressin (AVP) compared with phenylephrine (PE) or methoxamine. In normal rabbits, baroreflex inhibitions of HR and lumbar and renal SNA are all greater when MAP is increased by AVP vs. PE. The differential reflex bradycardic and renal sympathoinhibitory effects of AVP vs. PE in rabbits require an intact area postrema. To determine whether differential reflex effects of AVP vs. PE in rats is selective for HR or inclusive of renal SNA and to examine the role of the rat area postrema in such action, we monitored HR and renal SNA in normal (sham operated, n = 8) and area postrema-lesioned (APX, n = 8) rats under chloralose anesthesia during slow increases in MAP (less than 0.3 mmHg/s; 3 min) induced intravenously by AVP (0-16 mU.kg-1.min-1) and by PE (0-8 micrograms.kg-1.min-1). Reflex inhibition of HR ( delta betas.min-1.delta mmHg-1) was greater when MAP was increased by AVP vs. PE in normal rats (-2.7 +/- 0.5 vs. -1.7 +/- 0.1, P less than 0.05), and this difference was absent in APX rats (-2.5 +/- 0.5 vs. +/- -2.2 +/- 0.4). Similarly, maximum bradycardia (-delta beats/min) by AVP vs. PE was greater in normal rats ( 64 +/- 8 vs. -48 +/- 7, P less than 0.05) but not in APX rats (-53 +/- 5 vs. -52 +/- 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331016 TI - Electrophysiological effects of L-palmitoylcarnitine in single ventricular myocytes. AB - In isolated guinea pig ventricular myocytes, L-palmitoylcarnitine (L-PC) produced concentration- and time-dependent changes of resting potential (RP) and action potential duration at 50% repolarization (APD50). At 10(-8) to 10(-6) M, L-PC increased APD50 without changing RP. At 10(-5) M, the amphiphile initially increased (0-10 min) and eventually decreased (greater than 10 min) APD50; the membrane depolarized when APD50 decreased. Additionally, transient depolarizations (TDs) were consistently induced in 10(-5) M L-PC within 10 min, and TD amplitude progressively increased with continued exposure to L-PC. The TDs induced in L-PC were augmented by membrane depolarization, elevated extracellular Ca2+ concentration ([Ca2+]o), and increased number of stimuli. Elevated [Ca2+]o or neuraminidase treatment also allowed TDs. In neuraminidase, the changes of RP, APD50, and TD amplitude were qualitatively similar to those seen with L-PC. These results are consistent with the hypothesis that 10(-5) M L-PC causes intracellular Ca2+ overload. The blockade of L-PC and neuraminidase-induced TDs by ryanodine is consistent with the intracellular Ca2+ overload hypothesis. PMID- 2331017 TI - Lung inflation evokes reflex dilation of microvessels in rat skeletal muscle. AB - Lung inflation can reflexively decrease peripheral resistance, but effects on the microcirculation have not been determined. In this study, we examined the effects of lung inflation on microvessels in skeletal muscle. In anesthetized spontaneously breathing rats, the right cremaster muscle with intact circulation and innervation was exposed and suspended in a tissue bath filled with a physiological salt solution. Diameters of third-order arterioles (3As) were displayed by television microscopy and measured as an index of microcirculatory resistance. In other experiments, sympathetic activity (in the genital femoral nerve) to the cremaster was recorded. Lung inflation decreased systemic blood pressure by 32 +/- 3 mmHg and increased 3A diameter by approximately 23% (P less than 0.05, n = 17). The increase was abolished by cutting the cervical vagus nerves or the right genital femoral nerve. Furthermore, inflation decreased sympathetic nerve activity by 47.6 +/- 11.3% (P less than 0.05, n = 5) before vagotomy but not after. Dilation in response to inflation was also abolished by phentolamine or guanethidine. These results suggest that stimulation of vagal afferents by inflation reflexively decreases microvascular resistance by withdrawal of sympathetic tone. PMID- 2331018 TI - Elevated body temperature and increased blood vessel sensitivity in spontaneously hypertensive rats. AB - Body temperature (BT) was significantly greater in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rats regardless of the time of day, length of rectal probe, sex, age, or commercial vendor. Bath temperature (theta) for excised aortic rings was controlled by a thermoelectric Peltier module with an accuracy of 0.1 degree C. At peak force in individual contractions of norepinephrine (NE) dose-response experiments, theta was changed from 37 to 39 degrees C. Active and resting wall tension (Tw) were increased, and the mean effective dose (ED50) was decreased in the SHR aorta with and without endothelium. For the WKY aorta, active and resting Tw were increased, but ED50 was the same with and without endothelium. These results were supported by experiments where theta was decreased from 39 to 37 degrees C and by experiments on Sprague-Dawley rats. Potassium dose-response experiments with aorta from SHR and WKY rats show an increase in sensitivity at 39 degrees C, but active Tw is the same at 39 and 37 degrees C. When compared at the BT of each rat, the NE ED50 was lower and resting Tw was higher in the SHR aorta than in the WKY aorta, but active Tw was the same.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331019 TI - Cholinergic prejunctional inhibition of vasodilator nerve function in bovine basilar arteries. AB - Helical strips of bovine basilar arteries responded to transmural electrical stimulation with moderate relaxations that were abolished by treatment with tetrodotoxin and oxyhemoglobin and were significantly attenuated by quinidine, as were the relaxations previously seen in dog and monkey cerebral arteries. The relaxant response of the bovine arteries was attenuated by treatment with acetylcholine and physostigmine and was significantly potentiated by atropine. In contrast, relaxations of dog coronary arteries to transmural stimulation, mediated via beta-adrenoceptors, were not influenced by physostigmine and atropine but were attenuated by acetylcholine. Abundant fibers containing cholinesterase were histologically demonstrated in bovine basilar arteries, suggesting the presence of cholinergic innervation. Acetylcholine liberated from the cholinergic nerve appears to act on muscarinic receptors located in vasodilator nerve terminals in bovine cerebral arteries and to interfere with the release of vasodilator transmitters. PMID- 2331020 TI - Prevention of salt angiotensin II hypertension by servo control of body water. AB - An automated servo-control system to maintain total body weight constant was used to investigate the role of fluid volume expansion in the development of salt dependent hypertension in dogs continuously infused with subpressor doses of angiotensin II. Dogs maintained on a fixed salt and water intake were studied in metabolic scale cages, which enabled continuous 24 h/day monitoring of changes in body weight as an index of changes in total body water. Beat-by-beat hemodynamics were determined 24 h/day. Daily fluid and electrolyte balances and hormonal profile were determined. Blood volume was periodically measured by injection of 51Cr red blood cells. After a 3-day control period, salt intake was increased from 8 to 120 meq/day. In contrast to the rise of arterial pressure that was observed in our previous nonservo-controlled volume studies, average 24-h mean arterial pressure, cardiac output, and total peripheral resistance remained unchanged during a 4-day high-salt period. Total body weight was maintained within 7 +/- 17 g of the original weight. Blood volume was unchanged by day 2 as indicated by direct measurement (51Cr red blood cells) or by analysis of plasma protein concentration. There was a retention of 82 +/- 5 meq (P less than 0.05) of sodium on day 1 of high-salt period. Plasma sodium concentration increased approximately 7 meq/l (P less than 0.05) above control levels. Plasma renin activity and aldosterone decreased to undetectable values, whereas vasopressin and atrial natriuretic peptide increased significantly. These results confirm that elevations of blood volume and cardiac output normally observed when salt intake was increased in dogs infused with angiotensin II are secondary to water retention and that this salt-dependent model of hypertension is dependent on fluid volume expansion. PMID- 2331021 TI - Different effects of sodium or chloride depletion on angiotensin II receptors in rats. AB - We studied the effects of selective chronic sodium or chloride depletion (0.005% in diet) on central and peripheral angiotensin II receptors in young rats. Chloride depletion produced the most significant increase in plasma renin activity and extracellular fluid volume contraction. In the brain, subfornical organ angiotensin II receptor concentration was decreased by sodium depletion and increased by chloride depletion. There were no significant changes in angiotensin II binding in the paraventricular nucleus. When sodium-depleted rats were water deprived for 3 days, subfornical organ angiotensin II receptor concentration increased, showing that normal sodium intake was not essential for increased numbers of angiotensin II receptors during dehydration. In the adrenal gland, chloride depletion decreased angiotensin II receptors in the medulla and zona glomerulosa. Conversely, sodium depletion increased angiotensin II receptors in the zona glomerulosa. In the kidney glomeruli and medulla, angiotensin II receptors were decreased by either sodium or chloride depletion. These results suggest different roles for sodium and chloride in the regulation of the peripheral and central renin-angiotensin system in young rats. PMID- 2331022 TI - Assessing the characteristic between length of hypoxic exposure and serum erythropoietin levels. AB - We examined the relationship between the duration of hypoxic exposure and serum erythropoietin (EPO) production. Adult male Long-Evans rats were exposed to hypobaric hypoxia (HH = 0.5 atm) for a period of 15 min to 20 days. Serum for EPO by radioimmunoassay was collected immediately, 1 or 2 h after HH exposure. A significant rise in EPO levels occurred 1 h after a 30-min HH exposure that was not sustained 2 h after termination. One hour of HH exposure resulted in increased EPO levels 1 h after termination of exposure and further increased levels 2 h after termination of exposure. With prolonged exposure, serum levels remained elevated at 6 and 20 days, despite the development of polycythemia. We concluded that the hypoxic stimulus for elevation of serum EPO could be as short as 30 min and that EPO levels remained elevated after chronic HH. The experimental data were consistent with a mathematical model in which stimulated EPO production was proportional to the time of HH stimulus. PMID- 2331023 TI - Possible role of basolateral cell membrane in proximal renal tubule osmoregulation. AB - The cellular response to hypotonic stimulation was studied with videometric methods in 266 proximal renal tubules dissected from Carassius auratus (goldfish). In hypotonic solutions (low NaCl), cells underwent rapid swelling followed by gradual shrinking toward isotonic volume (volume-regulatory decrease phase, VRD). Hypothermia (8 degrees C), increased extracellular potassium (15, 25, and 40 mM), quinine (0.1 mM), barium (0.5 mM), 4,4'-diisothio-cyanostilbene 2,2'-disulfonic acid (DIDS; 0.02 mM), acetazolamide (0.1 mM), decrements in extracellular bicarbonate, and increases in extracellular chloride impaired VRD. Ouabain (1.0 mM), furosemide (0.1 mM), and the chloride channel blocker 5-nitro-2 (3-phenylpropylalanine) benzoate (NPPB; 0.001 mM) had no effect. While VRD occurred in the absence of extracellular calcium influx, addition of the calcium ionophore A23187 (0.01 mM) in the presence of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA; 2.0 mM) impaired this process both in acidic and alkaline media. Trifluoroperazine (0.01 mM) reversibly inhibited VRD. The effect of this calmodulin inhibitor could not be overridden with the cationic ionophore gramicidin (0.5 microM). The data suggest that Carassius proximal renal tubular cells volume regulate in hypotonic solutions by the loss of KCl and osmotically obligated water. We postulate that the main efflux of potassium is through a calcium-gated potassium channel with its counter ion extruded through a calmodulin-regulated Cl(-)-HCO3- exchanger. PMID- 2331024 TI - Association of DOCA hypertension with induction of atherosclerosis in rats with short-term diabetes mellitus. AB - We investigated the effect of deoxycorticosterone acetate (DOCA)-induced hypertension on plasma lipid and cholesterol levels and the development of vascular atherosclerotic changes in male Wistar rats injected with streptozotocin (STZ) or saline (CON). Rats given STZ alone demonstrated a mild hyperlipidemia and hypercholesterolemia without any change in blood pressure. One week of DOCA administration was without effect on blood pressure in CON and STZ groups, but at 3 and 6 wk caused a significant and similar elevation in both groups. This DOCA induced elevation in blood pressure appeared to be associated with the increase in plasma lipid and cholesterol levels seen in both CON and STZ groups at 3 and 6 wk, although the elevation in lipid and cholesterol levels was significantly more pronounced in the STZ rats. Both CON and STZ groups injected with DOCA developed significant pathological changes in all vessels under investigation. However, the degree of atherosclerosis appeared, from a semiquantitative analysis, to be worse in the thoracic aortas and renal arteries of the STZ group. Neither normotensive group developed any atherosclerosis. It is concluded that hypertension is associated with atherosclerosis in normal rats and rats with short-term STZ induced diabetes mellitus, although the higher plasma lipid and cholesterol levels of the latter group may potentiate the degree of vascular damage. PMID- 2331025 TI - Temperature regulation in biotelemetered spontaneously hypertensive rats. AB - Core temperature of the spontaneously hypertensive rat (SHR) was not found to be different from the core temperature of the control rat, the Wistar-Kyoto rat (WKY), when the rats were left undisturbed in their home cages. When the rats were exposed to a variety of stressful environments, including cage switching, exposure to an open field, and handling, both SHR and WKY rats showed an increase in temperature. For the set of rats supplied by Charles River, the SHR temperature response to the stress was identical to the WKY rats' temperature response. For the set of rats supplied by Taconic Farms, the SHR was found to have a greater temperature response to the acute stress and the open-field stress. The Taconic Farms rats were also exposed to restraint stress, which resulted in a rise in temperature that was greater for the SHR when compared with the WKY. Because we have observed the increased lability in body temperature of the SHR compared with the WKY rats during restraint, we believe that it is important that studies with these strains of rat be done using minimal or no restraint. PMID- 2331026 TI - Propranolol inhibits O2-sensitive chemoreceptor activity in trout gills. AB - The effects of propranolol on the activity of O2-sensitive chemoreceptors innervated by cranial nerve IX were studied using an isolated, perfused first gill arch preparation from rainbow trout (Onchyrhyncos mykiss). Perfusing the gill with hypoxic perfusate resulted in an increase in chemoreceptor activity. Propranolol (100-200 nmol) added to the perfusate inhibited O2-receptor discharge during both normoxia and hypoxia and attenuated the response to bolus injections of NaCN (25 micrograms). These results suggest that a beta-adrenergic mechanism is involved in O2 chemoreception. They further suggest that the inhibitory effects of propranolol on branchial, O2-sensitive chemoreceptors may contribute to the attenuated hypoxic ventilatory reflex observed in intact fish after propranolol injections. PMID- 2331027 TI - Scaled creatine kinase model. PMID- 2331028 TI - Circadian variation of thermoregulatory responses during exercise in rats. AB - Rats exercised on a treadmill at daytime lows and nighttime highs of circadian change in body temperature at two different work intensities [40 and 60% of maximal oxygen uptake (VO2max)] with the ambient temperature (Ta) at 24 degrees C. Immediately before exercise at 60% VO2max, rectal temperature (Tre) was 0.7 degrees C higher at night than during the day. During the exercise, Tre rose more during the day than at night, and Tre at the end of exercise was the same in the day as at night. Threshold Tre for tail vasodilation did not differ between day and night. Similar tendencies of Tre change and tail vasomotor response were observed at a work intensity of 40% VO2max, except that the rise in Tre was smaller than at the higher work intensity. On the other hand, threshold Tre for tail vasodilation spontaneously occurring in resting rats in a warm environment (Ta of 28 degrees C) was 0.7 degrees C higher at night than during the day. In conclusion, exercise in rats attenuates the differences in deep body temperature and threshold Tre for tail vasodilation seen between day and night. PMID- 2331029 TI - Effects of pyrogen administration on temperature regulation in exercising rats. AB - To study the mechanism of rise in body temperature during exercise, endogenous pyrogen was administered to exercising rats. At rest and at a neutral ambient temperature (Ta) of 24 degrees C, intravenous injection of recombinant human interleukin 1 (IL-1, 40 micrograms/kg) produced a 0.5 degree C rise in rectal temperature (Tre) from 37.4 degrees C. At Ta of 34 degrees C, at which Tre was 38.6 degrees C, Tre rise in response to IL-1 was only 0.2 degree C greater than when saline was used. In the first series of exercise experiments, rats ran on a treadmill after IL-1 or saline injection at two different work intensities (estimated at 40 and 60% of maximal oxygen uptake) at 24 degrees C Ta. At either work intensity, the magnitude of Tre rise after IL-1 injection was approximately 0.5 degree C higher than after saline injection. Threshold Tre for tail vasodilation increased when IL-1 was injected. The difference in the threshold Tre between the IL-1 and saline conditions was 0.5 degree C at either work intensity. Evaporative heat loss was also suppressed and metabolic heat production facilitated when IL-1 was injected. In a second series of experiments, IL-1 was injected after Tre reached a steady state (38.5 degrees C) during exercise. After IL-1 injection Tre increased another 0.5 degrees C, but after saline injection Tre did not change. These results suggest that body temperature rise during exercise is not induced merely by an insufficient capability of dissipating heat and that the thermoregulatory set point is reset during exercise. PMID- 2331030 TI - Vasopressinergic augmentation of cardiac baroreceptor reflex in conscious rats. AB - Experiments were performed on conscious, chronically instrumented rats to determine the contribution of V2-receptor activation in augmentation of cardiac baroreceptor reflex (BRR) sensitivity by arginine vasopressin (AVP). At least 1 wk before experimentation, rats were implanted with arterial and venous catheters, as well as with pulsed Doppler flow probes for measurement of cardiac output (CO). An initial set of experiments was performed to determine whether cardiac BRR sensitivity is enhanced by AVP in conscious rats. A series of pressor doses of either AVP or phenylephrine (PE) were administered on separate days (n = 8). The slope of pulse interval (PI) vs. mean arterial blood pressure (MABP) was determined for each experiment by linear regression and used as an index of cardiac BRR sensitivity. The slope of PI vs. MABP was greater in response to AVP than in response to PE in all animals studied. A separate group of animals (n = 7) received either a 40-min infusion of AVP (5 ng/min iv) or a specific V2 antagonist, d(CH2)5[DIle2,Ile4]AVP (20 micrograms/kg iv), 10 min before infusion of AVP. The responses of MABP, CO, and total peripheral resistance to AVP infusion were similar with and without V2-antagonism; however, the bradycardic response to AVP was less with V2-antagonist pretreatment. Furthermore, administration of V2-antagonist reduced delta PI/delta MABP in response to AVP infusion. Additional experiments were performed to test the effect of infusion of a specific V2-agonist, dVDAVP (5 ng/kg iv), on BRR-induced bradycardia in response to a series of pressor PE bolus doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331031 TI - Urea transport across urinary bladder and salt acclimation in toad (Bufo viridis). AB - The fluxes of urea across the urinary bladder of the toad Bufo viridis have been studied under conditions of acclimation to tap water or 500 mosM NaCl solution. The [14C]urea fluxes were measured simultaneously with [3H]inulin to test for nonspecific leakage. The fluxes are quite high (Ktrans = 75 x 10(-7) cm/s at 5 mmol/l urea) and are similar in either the mucosal-to-serosal or the opposite direction. "Summer" rates were five to six times higher than the "winter" rates. Antidiuretic hormone (ADH), theophylline, and forskolin increased the fluxes to variable degrees (two to five times), similar in the two acclimation conditions. Phloretin inhibited the urea fluxes by nearly 50%. 1,3-Dimethylurea and thiourea, but not acetamide, competed with the urea fluxes effectively. The fluxes of urea were not affected by the osmotic water flow, although both responded to ADH. It is concluded that urea transport across the urinary bladder of B. viridis is by facilitated diffusion through a specific pathway independent of water flux. The inhibitory effect of the structural analogues on the urea flux was affected by salt acclimation, whereas most other characteristics did not differ significantly at 5 mmol/l external urea under the two conditions of acclimation. PMID- 2331032 TI - Transuterine ion movement and electrical potential difference in pregnant guinea pigs. AB - An investigation of the site and mechanism responsible for the maternal-fetal electrical potential difference (PD) was done in 11 anesthetized guinea pigs at 54-56 days gestation. We removed the most distal fetus and placenta from one uterine horn and secured a catheter, thermistor, and Ag-AgCl electrode in the resulting pouch. The pouch was filled with Earle's solution. We placed another thermistor and electrode in the maternal abdomen. The PD between electrodes was monitored continuously; periodic samples of maternal blood and intrauterine fluid were taken. Thirty minutes after the uterus was filled, the PD (uterine cavity negative) averaged 29.6 +/- 4.5 (95% confidence interval of the mean) mV. Over 4 h, intrauterine K+ concentration [( K+]) decreased from 4.9 to 2.6 +/- 0.5 meq/l, against a chemical and electrical gradient. In eight animals, we measured bidirectional Na+ flux using 22Na and 24Na. The flux ratio was not distinguishable from unity despite a significant PD. Our data indicate that the maternal-fetal PD is probably generated by the endometrial epithelium and that Na+ and K+ both move across the epithelium by active transport or cotransport rather than simple diffusion. PMID- 2331033 TI - Effects of acute and chronic baroreceptor denervation on diving responses in ducks. AB - To investigate the effects of barodenervation on the cardiovascular responses to forced submersion, we implanted snares around the aortic nerves innervating the baroreceptors in anesthetized (pentobarbital sodium, 35-45 mg/kg) ducks (Anas platyrhynchos). Snares were withdrawn 1 wk after surgery to effect barodenervation in the absence of complications from surgical trauma or anesthesia. After barodenervation, resting heart rate (HR), hind limb vascular resistance (HLVR), and mean arterial pressure (MAP) all increased, with different time courses, over the 16-day observation period. Bradycardia developed during forced submersion in ducks before and after barodenervation, although this response was reduced for 1-3 days after nerve section. The HR response to diving intensified 4-5 days after denervation, and the level of dive bradycardia at 16 days was similar to that before denervation. End-dive MAP fell further, as a proportion of predive MAP, with time after baroreceptor loss. The absolute level of HLVR reached during diving was unaffected by barodenervation. These results show that diving responses develop in the absence of baroreceptors, but MAP in the dive is not maintained as well in barodenervates as in baroreceptor-intact animals. PMID- 2331034 TI - Glycogenesis from lactate in rabbit skeletal muscle fiber types. AB - The path of glycogen synthesis from three-carbon precursors was studied via single-pass perfusions in three distinct rabbit skeletal muscle preparations, i.e., glycolytic (greater than 99% type IIb), oxidative (greater than 97% type I), and mixed (type I, IIa, and IIb). The extent of interaction between the Krebs cycle and glycogenesis was assessed utilizing [1-14C]- or [2-14C]lactate at basal (1.1 +/- 0.1 mM) and elevated (8.1 +/- 0.3 mM) lactate concentrations (protocols 1 and 2). Under conditions in which the net balance of glucose and lactate, [14C]lactate removal, and venous lactate-specific activity were similar, the yields of 14CO2 and [14C]glycogen were not significantly influenced by position of the label. Additional perfusions were performed with lactate (8.0 +/- 0.1 mM) and acetate (1.0 +/- 0.1 mM) as sole substrates and either [U-14C]lactate or [2 14C]acetate as the tracer. Under conditions of net glycogen synthesis, the incorporation of [14C]lactate into glycogen [in disintegrations/min (dpm).g-1.2 h 1] was 40,940 +/- 3,320, 1,540 +/- 320, and 32,600 +/- 4,100 in the glycolytic, oxidative, and mixed preparations, respectively. However, no incorporation of [2 14C]acetate into glycogen was observed in any preparation, despite a significant yield of 14CO2. Mercaptopicolinic acid, a potent inhibitor of phosphoenolpyruvate carboxykinase (PEPCK), demonstrated no significant effect on net substrate balance, tracer uptake, net glycogen synthesis, incorporation of [14C]lactate and [3H]-glucose into glycogen, or 14CO2 yield. Current results suggest an extramitochondrial route for net glycogen synthesis from three-carbon precursors, exclusive of PEPCK, that is consistent across all mammalian skeletal muscle fiber types. PMID- 2331035 TI - Alteration of antioxidant enzymes with aging in rat skeletal muscle and liver. AB - Maximal activities of antioxidant enzymes involved in oxygen free radical metabolism in skeletal muscle and liver were investigated in 4-, 26-, and 31-mo old male Wistar-Furth rat at rest and after a single bout of treadmill exercise. In skeletal muscle, cytosolic (Cu-Zn) and mitochondrial (Mn) superoxide dismutase (SOD) specific activities were significantly higher in the aged rats and at 31 mo reached 135 and 218%, respectively, of those at 4 mo. Resting catalase activity was doubled at 31 mo compared with that at 4 mo. Glutathione peroxidase (GPX) activity increased twofold in muscle cytosol and by 47% in mitochondria of aged rats. Glutathione S-transferase (GST), glutathione reductase (GR), and glucose-6 phosphate dehydrogenase (G-6-PDH) activities in muscle were also significantly elevated. Hepatic antioxidant enzymes were altered differentially with aging. Cytosolic SOD and GST activities were decreased, whereas mitochondrial GPX, GR, and G-6-PDH activities were increased. Lipid peroxidation was greater in skeletal muscle homogenate and mitochondria but lower in liver homogenate in the aged rats. An acute exercise bout had little effect on muscle or liver antioxidant enzymes regardless of the animal's age. It is concluded that aging is accompanied with an elevation of antioxidant enzyme activities and lipid peroxidation in skeletal muscle probably due to the increased oxygen free radical production and reaction. PMID- 2331036 TI - Estrogen-induced modulation of hypothalamic osmoregulation in female rats. AB - Estrogen treatment of ovariectomized female rats for a week decreased plasma osmolality from 294 to 278 mosmol/kgH2O, but recordings from the whole animal preparation under urethan anesthesia failed to detect any change in the activity of 76 vasopressinergic neurons in the supraoptic nucleus (SON) of the hypothalamus. In brain slice preparations, neuronal discharge of 74 presumed vasopressinergic SON cells increased linearly as the osmolality of the perfusate was increased from 278 to 320 mosmol/kgH2O, each 10 mosmol/kgH2O fraction corresponding to a 0.7-Hz change. This osmolality-neuronal activity relationship was similar in the slices taken from the estrogen-treated and the control ovariectomized animals, except that the neurons in the former fired twice as frequently as those in the control throughout the osmolality range. This difference explains the estrogen-induced decrease in the osmolality threshold to elicit antidiuresis and the resultant water retention in estrogen-treated animals. It was reasoned that the estrogen-induced neuronal activation was offset by the decreased plasma osmolality in the animal as a whole. PMID- 2331037 TI - Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings. AB - In humans, the continuous release of Hg vapor from dental amalgam tooth restorations is markedly increased for prolonged periods after chewing. The present study establishes a time-course distribution for amalgam Hg in body tissues of adult and fetal sheep. Under general anesthesia, five pregnant ewes had twelve occlusal amalgam fillings containing radioactive 203Hg placed in teeth at 112 days gestation. Blood, amniotic fluid, feces, and urine specimens were collected at 1- to 3-day intervals for 16 days. From days 16-140 after amalgam placement (16-41 days for fetal lambs), tissue specimens were analyzed for radioactivity, and total Hg concentrations were calculated. Results demonstrate that Hg from dental amalgam will appear in maternal and fetal blood and amniotic fluid within 2 days after placement of amalgam tooth restorations. Excretion of some of this Hg will also commence within 2 days. All tissues examined displayed Hg accumulation. Highest concentrations of Hg from amalgam in the adult occurred in kidney and liver, whereas in the fetus the highest amalgam Hg concentrations appeared in liver and pituitary gland. The placenta progressively concentrated Hg as gestation advanced to term, and milk concentration of amalgam Hg postpartum provides a potential source of Hg exposure to the newborn. It is concluded that accumulation of amalgam Hg progresses in maternal and fetal tissues to a steady state with advancing gestation and is maintained. Dental amalgam usage as a tooth restorative material in pregnant women and children should be reconsidered. PMID- 2331038 TI - Differential osmoresponsiveness of periventricular neurons in duck hypothalamus. AB - Single-unit responses to osmotic stimulation were recorded extracellularly in slice preparations from the duck's hypothalamus in the periventricular layer (pl), magnocellular center (mc), and deep periventricular neuropil of the paraventricular nucleus (PVN). The pl neurons were located in the dorsorostral third ventricular region of maximum osmoresponsiveness determined in vivo. Hypertonic stimulation (+20 to +35 mosmol/kgH2O) by excess NaCl in the incubation medium excited 25 and inhibited 4 out of 48 pl neurons. Hypotonic (-10 to -20 mosmol/kgH2O) stimulation inhibited 9 out of 10 neurons activated by hypertonic stimulation. Hypertonic activation of pl neurons was maintained in seven out of nine neurons when NaCl was replaced by LiCl, but replacing NaCl by sucrose was ineffective in each of 10 neurons. Synaptic blockade (Ca2(+)-free/high-Mg2+ medium) did not abolish hypertonic activation in 8 out of 11 pl neurons. Among 30 mc neurons, 2 were activated and 1 inhibited by hypertonic stimulation with NaCl (+20 to +35 mosmol/kgH2O), and among 24 neurons in the periventricular neuropil, 2 were activated and 4 inhibited. The function of osmoresponsive pl neurons as specific receptors would be consistent with their morphological characteristics and with the location and functional properties of the duck's third ventricular osmoresponsiveness in vivo. PMID- 2331039 TI - Relation of plasma norepinephrine and sympathetic traffic during hypotension in humans. AB - We compared changes in antecubital venous plasma levels of norepinephrine (NE) and peroneal nerve muscle sympathetic activity (MSA) during and after nitroprusside (NP)-induced hypotension in nine healthy volunteers. During NP, MSA increased at 98.7%/min, peaked at 4 min at 399 +/- 77% (SE) of base line, and then decreased, so that at the end of the infusion MSA was 298 +/- 39% of base line. NE increased at 9.2%/min and peaked at 14.5 min at 231 +/- 31% of base line just before the end of the infusion. Percent increases of MSA and NE near the end of NP were not significantly different. The time-to-peak NE lagged the time-to peak MSA by nearly 10 min. These results suggest that during increases of sympathetic outflow diffusion and washout of NE from neuroeffector junctions result in delayed increases in NE in the venous drainage; percent changes in MSA and NE during prolonged stable mild hypotension are similar. The findings provide conditional support for the use of changes in NE to indicate changes in sympathetic traffic. PMID- 2331040 TI - Phase-shifting the light-dark cycle resets the food-entrainable circadian pacemaker. AB - This experiment examined coupling between two circadian pacemakers, one entrained by light and the other by food. Rats were housed in running wheels: one-half on restricted feeding from 0900 to 1100 h whereas the others were free fed. After timed-fed rats developed bursts of running before 0900 h, all rats were given free access to food. A month later, the light-dark (LD) cycles for one-half the rats in each group were delayed by 6 h. After entrainment to the new LD cycles, all rats were probed with 96-h periods of food deprivation. During these probes, unshifted timed-fed rats ran more than their free-fed controls at 0600-1200 h, but delayed timed-fed rats ran more than their controls at 1200-1500 h, i.e., 6 h later than unshifted rats. Next, the unshifted rats were subjected to a 6-h advance in their LD cycle. One month later, all rats were again probed with food deprivation. Delayed timed-fed rats continued to run more at 1200-1500 h than their free-fed controls, but timed-fed and free-fed phase-advanced rats showed similar activity patterns after the phase advance. However, when activity patterns before these probes were subtracted, timed-fed advanced rats showed greater "responses" to food deprivation at 0001-0300 h than their free-fed controls, i.e., 6 h earlier than before the phase advance. Thus LD shifts delayed and advanced the running that was previously associated with food availability and reset the food-entrainable circadian pacemaker. PMID- 2331041 TI - Selection of Phlebotomus papatasi (Diptera: Psychodidae) lines susceptible and refractory to Leishmania major infection. AB - Variation in susceptibility to infection with cultured promastigotes of Leishmania major was detected among 3 different geographic strains (ISRAEL, EGYPT, and INDIA) of the sand fly Phlebotomus papatasi. The ISRAEL strain showed the greatest susceptibility and was chosen for subsequent genetic selection experiments. After 13 generations of genetic selection in this strain, a stable refractory line was obtained in which only 7.5% of the insects could be infected. A highly susceptible line was also obtained in 5 generations of selection. Infection rates in the susceptible line were stabilized at about 94%. A description of the selection process and characteristics of the 2 lines are given. PMID- 2331042 TI - Genetic factors controlling susceptibility to Leishmania major infection in the sand fly Phlebotomus papatasi (Diptera: Psychodidae). AB - Studies of the genetic factors controlling Leishmania major infection in Phlebotomus papatasi were carried out using 2 different sand fly lines: one highly susceptible and the other refractory to the parasite. L. major infection rates in both F1 and F2 generations from reciprocal crosses and in backcrosses between the parent lines showed that susceptibility and refractoriness of Ph. papatasi to infection with L. major are controlled by less than 1 gene. Neither susceptibility nor refractoriness is dominant over the other. PMID- 2331043 TI - Growth kinetics of the Lyme disease spirochete (Borrelia burgdorferi) in vector ticks (Ixodes dammini). AB - Lyme disease spirochetes (Borrelia burgdorferi) multiplied rapidly in larval Ixodes dammini, reaching a mean density of 2,735 spirochetes/tick on day 15 post repletion. A 5-fold drop in spirochete levels occurred during the subsequent premolting period. Recently molted nymphs contained a mean of less than 300 spirochetes/tick. Following nymphal repletion, spirochete multiplication renewed, reaching a mean abundance of 61,275 spirochetes/nymph on day 75 post-repletion. A 10-fold drop in spirochete abundance occurred again when ticks molted to the adult stage. Tick-derived spirochetes proved to be infectious when greater than 10(4) spirochetes were inoculated ip into hamsters (4 of 4 animals infected). Inocula of 10(3-4) spirochetes were not always infectious (8 of 23 animals infected), and inocula of less than 10(3) spirochetes were insufficient for establishing infection (0 of 8 animals infected). PMID- 2331044 TI - Development of immunity to ocular chlamydial infection. AB - The development of "natural immunity" to homologous and heterologous ocular challenge with Chlamydia trachomatis was examined in cynomolgus monkeys given primary or secondary inoculations of C. trachomatis serovars B, C, and E. Overall, serovar E gave more severe disease than the other serovars. The amount of disease induced by the 2 serovar B strains examined, TW-5 and HAR-36, varied. In general, animals showed resistance to homologous secondary challenge, which was better characterized by a reduction in the recovery of culturable organisms than by a reduction in clinical disease. However, following initial heterologous challenge, neither resistance nor aggravation of disease was seen. These observations suggest that a trachoma vaccine will have to contain the serovar specific antigenic determinants for multiple chlamydial serovars. PMID- 2331045 TI - Spontaneous T cell proliferation and release of soluble interleukin-2 receptors in patients with HTLV-I-associated myelopathy. AB - Patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) show increased serum levels of soluble interleukin-2 receptors (sIL-2R), a marker of T cell activation. We found that peripheral blood lymphocytes from HAM patients proliferated spontaneously and released sIL-2R when cultured in vitro. Spontaneous proliferation was observed in T cell populations (both CD4+ cells and CD8+ cells), but not in B cell-rich populations or monocyte-rich populations. There was a significant increase of IL-2 activity in the culture supernatants of peripheral blood mononuclear cells (PBMC) after 2-3 days cultivation. On the other hand, sIL-2R concentrations in the supernatants were much higher after 5 days of cultivation. Such spontaneous T lymphocytic proliferation and release of sIL-2R were also found in non-HAM HTLV-I carriers, but not as intensely as in HAM patients. HTLV-I infection causes T cell activation to release IL-2 and sIL-2R; such T cell responses may play a role in the pathogenesis of HTLV-I-associated myelopathy. PMID- 2331046 TI - Acne keloidalis. Transverse microscopy, immunohistochemistry, and electron microscopy. AB - The earliest stages of acne keloidalis are not well characterized. In the present study, transverse sections of the early lesions revealed follicular units in several stages of inflammation. These follicles surrounded the central follicular units that gave rise to the clinically evident papule. Despite a spectrum of inflammatory changes, the most marked inflammation consistently occurred in the deep infundibular and isthmian levels of the hair follicles. Two follicles, presumably in the earliest stage, exhibited primarily an acute folliculitis and perifolliculitis, with destruction of the follicular wall and the release of hair. Central follicles showed predominantly acute neutrophilic or chronic lymphocytic inflammation at the upper isthmian levels and granulomatous inflammation at the deeper isthmian levels. Other follicles showed scar at the isthmian levels trapping hair fragments in the inferior portion of the follicle, with granulomatous inflammation and scarring. Sebaceous glands were absent in all stages of folliculitis in seven of eight follicular units. PMID- 2331047 TI - Immunohistochemical profile of cutaneous B-cell lymphoma on cryostat and paraffin sections. AB - Thirty cases of primary (23 cases) and secondary (seven cases) cutaneous B-cell lymphoma (CBCL) were studied by immunohistochemistry using a selected monoclonal antibody (MoAb) panel on both cryostat and paraffin sections. On cryostat sections all CBCL so tested were positive for surface membrane immunoglobulins (IgMk most often) and B-cell antigens (CD22+, CD37+) with a variable T-cell reactive component identified by MoAbs against T-cell antigens (CD2, CD3, CD4, CD5, CD8). CD4-positive stromal T-cells were usually more numerous than CD8 positive cells. A strong (50-75% of total cells) stromal T-cell (CD2+, CD3+) reaction was found in centroblastic-centrocytic lymphoma. Small numbers of CD1+ Langerhans cells were found in most cases, but they were present in large numbers in follicular lymphoma. On paraffin sections, a combination of MoAbs against B associated antigens (LN-1, MB2) identified B-cell lineage in virtually all cases of CBCL. CBCL was negative for MoAbs against T-associated antigens (MT1, UCHL1) with rare exceptions (two cases). However, MT1 and UCHL1 combined identified the T-cell nature of all cases of nonepidermotropic, nonmycosis T-cell lymphoma, which were initially predictive of B-lineage by histologic pattern. PMID- 2331048 TI - Squamous syringometaplasia in lobular panniculitis and pyoderma gangrenosum. AB - Squamous metaplasia of eccrine sweat glands has been most frequently described in chronic cutaneous ulcerations with associated epidermal hyperplasia. We found examples of the process in skin biopsy specimens from five patients: three had associated lobular panniculitis and two had lesions of pyoderma gangrenosum. The metaplasia was located in the mid-to-deep reticular dermis in all five patients and extended into the superficial subcutis in one. Immunohistochemical stains for CEA and S-100 protein were used to accentuate the relationship of the metaplastic islands with eccrine ducts. It is postulated that necrosis of a portion of the eccrine duct is the stimulus for this process. PMID- 2331049 TI - Histological analysis of intraepidermal proliferations of atypical melanocytes. AB - Fifty cutaneous pigmented lesions characterized by an intraepidermal proliferation of atypical melanocytes were reviewed. Several histological parameters (position of melanocytes in the epidermis, nuclear melanocytic atypia, presence or absence of pagetoid melanocytes, nucleoli, and others) were evaluated. On the basis of the results, the investigated cases were classified into three groups. In group 1, pagetoid melanocytes were present, melanocytic atypia was severe and continuous, all epidermal layers were involved by melanocytic proliferation, and a pattern of epidermal infiltration was recognized. In group 2, pagetoid melanocytes were absent, melanocytic atypia was mild-moderate and discontinuous, the lower epidermis only was involved by melanocytic proliferation, and a pattern of epidermal pseudoinfiltration was recognized. Group 3 cases were in an intermediate area between the two major groups. The results showed that intraepidermal proliferations of atypical melanocytes lie on one line, in which groups 1 and 2 account for the extremes. PMID- 2331050 TI - AgNORs in benign, dysplastic, and malignant melanocytic skin lesions. AB - Nucleolar organizer regions (NORs) are loops of DNA situated on the short arms of acrocentric chromosomes 13, 14, 15, 21, and 22; they can be demonstrated in formalin-fixed paraffin-embedded sections by a one-step silver technique, the resulting black structures being termed AgNORs. We have applied the technique to 30 benign "banal" nevi (BN), 30 dysplastic nevi (DN), and 30 malignant melanomas (MM). AgNORs in 200 nuclei were scored and the means calculated. Counts were as follows: BN showed a mean of 1.3 AgNORs per nucleus within a range of 1.1-1.6; DN showed a mean of 1.2 within a range of 1.0-1.6; and MM showed a mean of 2.1 within a range of 1.2-4.2. A significant difference existed between counts for MM and those for BN and DN, despite some overlap. There was no statistically significant difference between BN and DN. Although still within the field of research, the AgNOR technique may prove to be of value in helping to differentiate MM from DN, but is unlikely to be of help in separating DN from BN. PMID- 2331051 TI - Osteosarcomatous changes in malignant melanoma. Immunohistochemical and ultrastructural studies of a case. AB - Immunohistochemical and ultrastructural studies were conducted to elucidate the nature and origin of osteosarcomatous changes in malignant melanoma in a 43-year old Japanese man. Immunohistochemical studies with the use of antisera against human S-100 protein and neuron-specific enolase demonstrated positive reactions in the tumor cells within the osteosarcomatous area. Ultrastructurally, the neoplastic cells showed marked similarities to those from osteosarcomas. Additionally, occasional neoplastic cells contained round or ellipsoidal osmiophilic organelles, presumably melanosomes. These findings indicate that osteosarcomatous changes in malignant melanoma are produced by the dedifferentiated melanoma cells. PMID- 2331052 TI - Trichogenic trichoblastoma. An unusual neoplasm of hair germ. AB - Tumors of hair germ are a very rare group of primary cutaneous neoplasms that have been divided into two groups: epithelial and mesenchymal. Epithelial neoplasms of hair germ are further subdivided into those that are purely epithelial (trichoblastomas) and into epithelial neoplasms with mesenchymal components that may cause inductive changes toward the earliest phase of hair follicle differentiation (trichoblastic fibroma) or a more advanced and complete hair follicle formation (trichogenic trichoblastoma). We herein report an ulcerated trichogenic trichoblastoma whose epithelial and mesenchymal components recapitulated the formation of numerous primitive dermal papillae of the hair bulb because there were numerous strands of small polygonal epithelial cells that delimited areas of a dense and abundantly cellular connective tissue in a hair papilla-like pattern. PMID- 2331053 TI - Are dermatopathologists not socially conscious? PMID- 2331054 TI - [Use of fentanyl for anesthesia induction in cesarean section. Pharmacokinetics and pharmacodynamics in mother and child]. AB - A group of 36 patients in the last trimester of pregnancy and scheduled for cesarean section were examined during the induction of standardized general anesthesia (methohexitone 1.5 mg/kg, succinylcholine 1.5 mg/kg). No other inhalation anesthetics than N2O/O2 (50%:50%) were administered. In addition, 18 of the women received 0.005 mg/kg fentanyl prior to intubation. The remaining 18 patients served as a control group. In the study group maternal fentanyl plasma levels were determined 1 min after injection and again at the time of omphalotomy (radioimmunoassay). Immediately after clamping of the umbilical cord the fetal fentanyl plasma levels and the pH, pCO2 and pO2 values in both umbilical vein and artery were measured. The feto-maternal ratio and the fetal uptake were calculated. RESULTS. Maternal fentanyl plasma levels decreased significantly, from 7.84 (3.55-17.24) ng/ml 1 min after injection to 5.92 (2.01-14.15) ng/ml during omphalotomy. The corresponding fentanyl plasma levels in the umbilical vein were 2.08 (0.88-3.42) ng/ml. The feto-maternal ratio was 0.44 (0.08-1.00). The induction-delivery time ranged from 2 to 8 min. There was a significant correlation between umbilical-venous fentanyl concentration and the induction delivery time: the longer the induction-delivery time the lower the fentanyl concentration in the umbilical vein. The 1-min Apgar score was 8 (5-9), the 5-min Apgar score 9 (8-10) and the 10-min Apgar score 10 (9-10) in neonates born to the fentanyl group. Only the 1-min Apgar score was significantly lower than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331055 TI - [Hemo- and cardiodynamic action of halothane or isoflurane following peroral long term pretreatment with nifedipine. An animal experimental study]. AB - This study investigated the influence of chronic oral nifedipine on the hemodynamic effects of halothane or isoflurane anesthesia in dogs. Under general anesthesia with fentanyl 0.3 microgram/kg/min i.v. and 3:1 N2O/O2 inhalation mixture a left thoracotomy was performed and two needle force probes were placed in the left ventricular wall to measure myocardial force of contraction. In the halothane group (n = 12) a Hall-effect sensor was placed on the anterior surface of the left ventricle, which in combination with a magnet on the posterior surface allowed measurements of left ventricular diameter. In the isoflurane group (n = 15) a Widney gauge was placed around the left ventricle to measure left ventricular circumference changes. The dogs were also monitored with left ventricular tip manometers, pulmonary arterial thermodilution catheters, and femoral arterial and venous catheters. Prior to surgery, in the halothane group 6 dogs were pretreated with nifedipine 6 mg/kg p.o. for 10 days; the other 6 served as controls. In the isoflurane group, 8 dogs were pretreated with nifedipine in the same way and 7 served as controls. Three hours after instrumentation baseline hemodynamic measurements were performed and repeated 15 min after adding 1 MAC and then 2 MAC halothane or isoflurane. Oral pretreatment with nifedipine caused vasodilation with a significant decrease in systemic vascular resistance (SVR) and mean arterial pressure (MAP); heart rate (HR) and dp/dt max were unchanged in comparison to the control group. The cardiac output (CO) increased. Halothane (1 MAC/2 MAC) had a dose-related circulatory depressant effect. This occurred to the same extent in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331056 TI - [The preoperative outpatient clinic--possible use of a personal computer]. AB - Since 1977, the Department of Anesthesiology of the University of Graz has had a preoperative clinic. Since August 1988 we have processed current data using a personal computer (PC). We have adapted an IBM-compatible PC and a commercial data-processing program (dBase III plus) for the special requirements of the preoperative clinic. The procedure is directed by menus and is also easy to learn for non-professionals. Important functions have been executed automatically by the current program, such as loading the software or securing the data on a floppy disk. No additional work is necessary for data input. Every test result can be supplied immediately by a printer, whereby important parameters are denoted as such. After 13 months of testing, we could see that the use of a PC offers an inexpensive possibility for processing medical data with the help of electronics. The installation was not destined to remain a short trial, but will become a permanent system at our clinic. PMID- 2331057 TI - American Association of Anatomists, one hundred and third annual meeting. April 22-25, 1990, Philadelphia, Pennsylvania. Abstracts. PMID- 2331058 TI - Absence of cartilage canals in the long bone extremities of four species of skeletally immature marsupials. AB - The cartilaginous epiphyses and physes from the bone extremities of four species of skeletally immature marsupials were studied. The microscopic and ultrastructural features of the marsupial tissues were compared with similar samples from a neonatal lamb and a 1-day-old chick. Chondrocyte differentiation and endochondral ossification appeared similar in physes from the marsupials, foetal lamb, and 1-day-old chick. However, unlike the lamb and chick, which both contained cartilage canals, there were no cartilage canals in the epiphyseal or physeal cartilage from the marsupials. Many of the epiphyseal chondrocytes from the marsupial specimens contained large lipid droplets. It is suggested that the lipids in marsupial chondrocytes may be utilized in metabolic pathways. Despite hypertrophy of chondrocytes, there were no epiphyseal ossification centers in the femoral heads of the marsupial specimens; this was possibly due to the absence of cartilage canals, which are considered a source of osteoproginator cells. This study indicates that physeal and epiphyseal cartilage in marsupials is viable and functions in an avascular environment; this may be due to unique metabolic properties of the chondrocytes. PMID- 2331059 TI - Melano-macrophage centers in the aglomerular kidney of the sea horse (teleosts): morphologic studies on its formation and possible function. AB - In order to elucidate the process of the formation and possible function of the renal "melano-macrophage centers (MMC)" of fish, light and electron microscopic observations were carried out on the aglomerular kidney of the sea horse, Hippocampus kuda BLEEKER, injected with antigenic horse-spleen ferritin (AF) and nonantigenic carbon particles (CP). Kidneys of the sea horse have well-developed hemopoietic foci in the interstitial tissues surrounding the bundles of renal tubules. Each hemopoietic focus has a small artery in the central area and is framed with the densely arranged sinusoids lined with monolayered macrophages which have no melanin pigments. In the hemopoietic foci free macrophages (M phi) were hardly found, but large clusters of MMC filled with densely packed masses of cell debris with some melanin pigments were encountered. Some of them had degenerated M phi with fibrotic change surrounded by fibroblasts. AF and CP injected intraperitoneally entered quickly into blood vessels and were taken up actively by the sinusoidal M phi. The M phi full of AF or CP left the sinusoidal wall and moved gradually into hemopoietic foci to form the MMC or to fuse with the preexisting MMC. The melanophores in the interstitial connective tissue joined to form the MMC. No specific histologic change suggestive of immune response to the AF was present in and around the MMC. The results indicate that the MMC of fish should be only the aggregates of M phi to digest the ingested materials effectively. The process of formation of MMC and their possible function is discussed. PMID- 2331060 TI - Ultrastructural localization of acetylcholinesterase in the guinea pig pineal gland. AB - The ultrastructural localization of acetylcholinesterase (AChE) activity in guinea pig pineal gland was studied using the copper-glycine procedure. A small number of pinealocytes and bundles of unmyelinated nerve fibers were labeled by the AChE reaction. The AChE-positive pinealocytes were located near blood vessels and distributed in small groups. The AChE reaction product was localized in the perinuclear cistern, in the cisternae of the endoplasmic reticulum (ER), and in the saccules of the Golgi apparatus. These findings suggest that the AChE positive pinealocytes synthesize AChE. The AChE reaction product was also seen in the intercellular space between pinealocyte processes. Besides pinealocytes, AChE activity was localized on the axolemma of myelinated and unmyelinated nerve fibers and in the basement membrane surrounding unmyelinated nerve fibers. Pseudocholinesterase activity was confined to Schwann cells, which showed the reaction product in their perinuclear cistern, in the cisternae of the ER, and on the plasmalemma. PMID- 2331061 TI - Three-dimensional reconstruction of adult female mouse submandibular gland secretory structures. AB - Computer-assisted reconstructions of adult female mouse submandibular gland have been used to positionally characterize within the three-dimensional structure likely intermediates in secretory cell replacement. The locations of striated granular duct cells and granular intercalated duct cells are consistent with a role as intermediates between intercalated duct cells and granular duct cells or acinar cells, respectively. Average volumes of the two putative intermediate cell types are also consistent with this role. The reconstructions suggest that, in addition to a "streaming" mechanism for secretory cell replacement, formation of new secretory structures composed of multiple acini and second-order intercalated ducts may also contribute to the cell replacement process. PMID- 2331062 TI - Peripubertal human breast development. AB - The microanatomical and histological appearance of the human breast has been studied during puberty. The macroscopic architecture of the mammary epithelial tree was identified and correlated with the histological appearance of material excised from defined regions of the breast preparations. Between ages 13 yrs and 15 yrs the human breast shows evidence of ductal elongation and branching, with lobules formed by lateral and dichotomous branching. The majority of ducts are lined by a two-layered epithelium consisting of recognisable myoepithelial and luminal cells. Less-well-defined multilayered regions were also observed in some areas, apparently at the site of lateral branching or early lobular development. PMID- 2331063 TI - Single-dose interpleural versus intercostal blockade: nerve block characteristics and plasma concentration profiles after administration of 0.5% bupivacaine with epinephrine. AB - Analgesic effects and plasma concentration profiles after interpleural (IP) or intercostal (IC) administration of 21 mL of 0.5% bupivacaine with epinephrine (5 micrograms/mL) were studied in 24 patients (IP group: n = 12; IC group: n = 12) who had undergone cholecystectomy or renal surgery. The number of blocked dermatomes, as assessed by pinprick, was more variable between patients in the IP group (2-9 dermatomes) than in the IC group (6-8 dermatomes). The mean time intervals from the injection to two-dermatome regression and to first need for additional pain medication were 4 h (IP) and 5.5 h (IC) (P less than 0.02) and 5.3 h (IP) and 9.8 h (IC) (P = 0.002), respectively. The degree of postoperative pain was evaluated by means of a visual analogue scale. This gradually increased during the first 4 h in the IP group (P less than 0.001), but not in the IC group. Peak bupivacaine concentrations in arterial plasma were approximately 10% higher than those in venous plasma and were attained more rapidly. Peak arterial plasma concentrations after IP injection (2.07 +/- 0.53 micrograms/mL) were significantly higher (P less than 0.005) than those after IC administration (1.36 +/- 0.48 micrograms/mL). Peak venous plasma concentrations showed a similar difference (IP: 1.86 +/- 0.45 micrograms/mL; IC: 1.21 +/- 0.48 micrograms/mL; P less than 0.005). Peak concentrations were attained later after IP injection both in arterial (IP: 16.3 +/- 4.6 min; IC: 8.8 +/- 5.4 min; P less than 0.002) and venous plasma (IP: 20.0 +/- 7.1 min; IC 13.3 +/- 6.9 min; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331064 TI - Is chronic ethanol consumption associated with tolerance to intrathecal lidocaine in the rat? AB - Intoxication with alcohols can produce anesthesia. In contrast, chronic ethanol consumption can produce tolerance to inhaled and other general anesthetics. We tested whether ongoing consumption decreased, and whether withdrawal from such consumption increased, the intrathecal dose of lidocaine that induces sensory and motor blockade in female Sprague-Dawley rats. Sensory blockade was assessed using the tail-flick test, and motor blockade by the animal's inability to move its hind limbs. Rats were tested before commencing ethanol intake; during ethanol ingestion (9 days after beginning ingestion); and on the 15th day of ingestion, 14 h after withdrawing ethanol from their diet. Pair-fed control rats were tested at the same intervals. Ongoing administration of ethanol decreased the dose of lidocaine required to produce sensory blockade, but this difference was not significant relative to the control group (i.e., the difference was significant within group but not across groups). Withdrawal of ethanol increased the dose requirements for sensory and motor blockade by 80% and 53% (P less than 0.01 and P less than 0.0001) and decreased the duration of the motor blockade (P less than 0.01). Dose requirements producing sensory block differed between alcoholic and control groups (P less than 0.0001). These results suggest that chronic ethanol intake produces tolerance to the local anesthetic effects of lidocaine. Whether this change results from a change in kinetics or in sensitivity is not known, but the latter would seem more likely, because duration of blockade was minimally affected or unaffected. PMID- 2331065 TI - Effect of nifedipine on morphine-induced analgesia. AB - Experimental data show that opiates interfere with calcium influx in the cell and that some calcium-channel blockers are analgesic. We therefore studied the effect of the calcium-receptor blocker nifedipine on the analgesic effect of morphine in the rat, using tail-flick responses, and in humans, using measurements of the intensity of postoperative pain. In both the experimental animals and humans nifedipine significantly (P less than 0.001) increased the analgesic effect of morphine independently of any effect on the metabolism of morphine. Respiratory and cardiovascular functions were not significantly changed by nifedipine. The data indicate that Ca2+ is important in mediating the analgesic effects of opiates and suggest that calcium-receptor blockers might find a place in the treatment of pain. PMID- 2331066 TI - Cooling potentiates lidocaine inhibition of median nerve sensory fibers. AB - To determine the effect of cooling on lidocaine potency, nine consenting volunteers underwent bilateral median nerve blocks using 1% lidocaine HCl solution. Room-temperature and ice-cold lidocaine were injected into either dominant or nondominant wrists. Subjects were blinded to the temperature of the anesthetic. Inhibition of A alpha sensory and motor fibers was assessed as the decline in sensory nerve action potentials and compound motor action potentials, respectively. Inhibition of C fibers was measured as an increase in skin temperature and a decline in galvanic skin potentials. All indices of nerve function demonstrated profound (P less than 0.001) time-related changes after injection of local anesthetic. When ice-cold lidocaine was injected, inhibition of sensory nerve action potentials was significantly greater at all time points (P = 0.001) than when room-temperature lidocaine was injected. Inhibition of C fibers as assessed by galvanic skin potentials was marginally faster (P = 0.07) when ice-cold lidocaine was used compared with room-temperature lidocaine. No differences between room-temperature and ice-cold lidocaine were observed in inhibition of compound motor action potentials, or in the increase in skin temperature. We conclude that inhibition of median sensory fibers may be increased by cooling 1% lidocaine HCl in an ice bath before injection. PMID- 2331067 TI - Postoperative sore throat: effect of oropharyngeal airway in orotracheally intubated patients. AB - The incidence of postoperative sore throat was evaluated prospectively in 203 orotracheally intubated patients undergoing general anesthesia for surgical procedures. Patients were randomly assigned to have either a plastic oropharyngeal airway or a gauze bite-block in place during the operation and were evaluated for the occurrence of postoperative sore throat by questionnaire the day after surgery. The incidence of postoperative sore throat was 35.2% in the oropharyngeal airway group and 42.5% in the gauze bite-block group, not a statistically significant difference (P greater than 0.05). The incidence of postoperative sore throat was significantly higher when blood was noted on the airway instruments (64.5%) than when it was not (30.9%) (P less than 0.01). There was an association, although not statistically significant, between the incidence of postoperative sore throat and intubation by an anesthesia resident with less than 1 yr experience (P = 0.064). The data from this study indicate that the intraoperative use of hard plastic oropharyngeal airways, compared with the use of soft gauze bite-blocks, does not increase the incidence of postoperative sore throat. These data also suggest that pharyngeal trauma may contribute significantly to the development of postoperative sore throat. We suggest that aggressive oropharyngeal suctioning may contribute to this pharyngeal trauma. PMID- 2331068 TI - Hearing loss after spinal anesthesia is related to needle size. AB - Audiograms were performed preoperatively and 2 days postoperatively in 28 patients given spinal anesthesia for transurethral resection of the prostate. In 14 patients 22-gauge and in 14 patients 26-gauge spinal needles were used. Hearing loss of 10 dB or more at any frequency was observed in 13 of 14 patients in the 22-gauge group and in 4 of 14 patients in the 26-gauge group. There was a statistically significant reduction in hearing level in the low-frequency range in patients in whom the 22-gauge needle was used. Hearing loss was unilateral at five frequencies and bilateral at one frequency. No cases of postspinal headache occurred. Audiometry may be a more sensitive indication of cerebrospinal fluid leak than postspinal headache. PMID- 2331069 TI - Blood gas analysis of mixed venous blood during normoxic acute isovolemic hemodilution in pigs. AB - Mixed venous oxygen saturation of hemoglobin (SvO2) and mixed venous oxygen tension (PvO2) may reflect the overall balance between oxygen consumption and delivery. Because of the potential value of monitoring SvO2 and PvO2 as indications of the state of tissue oxygenation, the aim of this study was to determine, during normoxic acute isovolemic hemodilution in pigs, the critical PvO2, critical SvO2, and critical oxygen extraction ratio (ER) at which oxygen uptake starts to decline during further induced hemodilution. During stepwise induced isovolemic hemodilution, a gradual decline in SvO2 and PvO2 was observed in all animals. The mean +/- SD of the critical PvO2 of six animals was 32.3 +/- 3.1 mm Hg. The mean +/- SD of the critical SvO2 was 44.2% +/- 7.9%. The ER increased gradually. At an ER of 0.57 +/- 0.08, oxygen uptake started to decline. A significant correlation was found between changes in SvO2 and changes in ER. These degrees of hemodilution were accompanied by an increase in cardiac index, pulmonary wedge pressure, heart rate, and left ventricular stroke work index. Only a slight decrease in systemic vascular resistance was observed. We conclude that measurements of PvO2 and SvO2 can be used as indicators of the critical point of hemodilution and that the SvO2 during hemodilution reflects the overall balance between oxygen uptake and oxygen delivery, confirmed by the strong correlation found between SvO2 and oxygen extraction ratio. PMID- 2331070 TI - Effect of enflurane on contractile reactivity in isolated canine mesenteric arteries and veins. AB - The effects of enflurane on responses of isolated canine mesenteric arteries and veins to transmural nerve stimulation and to exogenously administered norepinephrine (a mixed alpha 1- and alpha 2-adrenoceptor agonist), phenylephrine (a selective alpha 1-adrenoceptor agonist), and tyramine were studied. The contractile responses of the arteries and the veins to transmural nerve stimulation and to norepinephrine were attenuated by exposure to enflurane; the responses to phenylephrine were decreased more than those to norepinephrine. When compared with the effect of enflurane on transmural nerve stimulation-induced responses, exposure to enflurane resulted in slight attenuation of the contractile responses caused by tyramine, suggesting that enflurane may inhibit the responses to tyramine by interfering with an interaction between released norepinephrine and postjunctional alpha 1-adrenoceptors rather than with tyramine induced norepinephrine release. The data are also consistent with the view that enflurane acts on sympathetic nerve endings to inhibit release of norepinephrine associated with electrical stimulation-induced nerve membrane depolarization. PMID- 2331071 TI - Epinephrine and phenylephrine increase cardiorespiratory toxicity of intravenously administered bupivacaine in rats. AB - We studied the effects of epinephrine and phenylephrine on the cardiorespiratory toxicity of intravenously injected bupivacaine in Sprague-Dawley rats. Our data show that both epinephrine and phenylephrine significantly increased cardiorespiratory toxicity of intravenously injected bupivacaine (P less than 0.007, X2 analyses with Yates' correction). Our data suggest that epinephrine or phenylephrine added to bupivacaine may be more toxic to cardiorespiratory systems than plain bupivacaine or epinephrine alone or phenylephrine alone when injected intravenously in rats. PMID- 2331072 TI - Percutaneous pulmonary artery catheterization in pediatric cardiovascular anesthesia: insertion techniques and use. PMID- 2331073 TI - Intravenous injection of liquid halothane. PMID- 2331074 TI - Prophylactic epidural blood patch in obstetrics. PMID- 2331075 TI - Ordinal data are not interval data. PMID- 2331076 TI - Prior gastric surgery and the risk of regurgitation. PMID- 2331077 TI - Desipramine potentiates anesthetic and lethal effects of ketamine. PMID- 2331078 TI - Monoclonal antibody differentiates chicken A system alloantigens. AB - A monoclonal antibody (ISU-cA) was produced that recognized certain alloantigens of the chicken A blood group locus. Antigens produced by alleles A3, A4 and A8 were positive, and those produced by A2 and A5 were negative, by haemagglutination. The specificity of ISU-cA for chicken A blood group antigens was demonstrated by serologic analyses, genetic crosses and competitive inhibition of binding by anti-A alloantisera. To our knowledge, this is the first reported monoclonal antibody against a chicken blood group alloantigen system other than the B complex. PMID- 2331079 TI - Isolation and characterization of two male-specific DNA fragments from the bovine gene. AB - Two independent male-specific DNA fragments were isolated from the bovine genome by the technique of cloning by deletion enrichment. Each is represented in the order of one to five copies per haploid genome. Neither fragment was found to be polymorphic between two individuals of different breeds with 12 different restriction enzymes. A 'zoo blot' demonstrated that one fragment had a closely related sequence in the sheep genome, although no other hybridizing sequences were detected in a variety of animal DNAs tested with both probes. The DNA sequence of each fragment is presented; one fragment has a continuous open reading frame and a potential Z-DNA forming region. PMID- 2331080 TI - Population data and a fourth allele for equine complement component 3 (C3). AB - The C3 polymorphism of equine serum or plasma revealed by agarose gel electrophoresis can be diagnosed with protein stain following acid protein fixation. In addition to the three alleles previously described (C31, C32, C33), a fourth allele (C34) was found. Population data for 25 domestic breeds and Equus przewalskii are presented. PMID- 2331081 TI - Genetic variation and distances of five Italian native sheep breeds. AB - Genetic distances among five of the most important Italian native sheep breeds were estimated by using gene frequencies of four blood group and seven blood protein loci and by three different computing methods. The values of the three distance matrices were highly correlated. Genetic distances were found within the range values reported in the literature for local breeds. Shorter distances fitted the historical evidence of migrations. PMID- 2331082 TI - [Effects of propofol on intraocular pressure in surgery of strabismus in children]. AB - Propofol was assessed for eye surgery in 20 children. ASA group I or II, 2-14 year-old, randomly assigned to 2 equal groups. Premedication, analgesia and muscle paralysis were similar in both groups. Group P patients were given an induction dose of 4 mg.kg-1 propofol, followed by an infusion of 15 mg.kg-1.h-1 for the first half hour, and then 10 mg.kg-1.h-1 to maintain anaesthesia. Group C patients were given 10 mg.kg-1 thiopentone for induction and halothane for maintenance. The quality of anaesthesia was assessed by monitoring adverse effects, heart rate, blood pressure, the length of anaesthesia, the delay of the first spontaneous breath and eye opening, and extubation. Intraocular pressure was measured before and 3 min after intubation, and 5 min after extubation. The quality of anaesthetic induction and maintenance were very similar in both groups. Pain occurred more frequently at the injection site with propofol (p less than 0.01). Children in group P recovered more quickly, and extubation was possible much earlier in this group (p less than 0.05). However, restlessness was significantly more frequent in group P (n = 9) than in group C (n = 1) (p less than 0.01). Systolic, diastolic blood pressure and heart rate were significantly lower in group P (p less than 0.05; 0.001; 0.001 respectively). No significant decrease in intraocular pressure in both groups was observed. The use of propofol for eye surgery in children is acceptable, despite some restlessness during recovery. PMID- 2331083 TI - [Tolerance and efficacy of delayed autologous transfusion in cardiovascular surgery]. AB - Over a period of 18 months, 313 patients (mean age 52 years) undergoing elective cardiovascular surgery were included in the autologous transfusion program involving two different Transfusion Centres. A further 10 patients were excluded because of anaemia (haemoglobin levels less than 11 g.dl-1) (n = 3), angina pectoris less than 8 days before (n = 3), patient refusal (n = 2), pneumonia (n = 1), and severe aortic insufficiency (n = 1). A maximum of 5 ml.kg-1 of blood was obtained during the 3 to 4 weeks prior to surgery, one donation being taken a week. In one Transfusion Centre, the blood was taken without tourniquet, and without any fluid replacement. Diuretics and converting enzyme inhibitors were stopped. In the opposite, in the other Centre, blood was taken using a tourniquet, and replaced by a gelatin solution (Plasmion). All the patients were given iron. The blood units were kept by the Transfusion Centres under the same conditions as homologous blood, but in a separate circuit. The 313 patients predeposited a mean of 2.71 units of blood: 4 units where obtained in 59 patients, 3 in 113, 2 in 133 and only 1 in 8. Mean haemoglobin level on starting the program was 14.49 g.dl-1. Neither homologous red cells nor plasma was administered in 176 patients (56.23%); among the 172 patients who predeposited 3 or 4 units, 123 (71.5%) were given their own blood only. Intraoperative blood salvage was used in 189 out of 313 patients (60.4%), and intraoperative haemodilution with albumin was used in 173 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331084 TI - [Anesthetic technics for the difficult intubation]. AB - Numerous anaesthetic techniques exist for a patient who presents with a difficult endotracheal intubation. They all require an anaesthetic protocol which cannot be improvised. When intubation is expected to be difficult at the pre-anaesthetic examination, the use of a fiberoptic bronchoscope is the technique of choice for intubating adults under local anaesthesia, and children under general anaesthesia. When a fiberoptic bronchoscope is not available, several alternatives can be suggested: local anaesthesia of the glottis, retro-molar and retrograde intubation, or the use of a guide threaded over a lighted stylet; these techniques can be used in an anaesthetized patient breathing spontaneously. In the paralyzed patient impossible to intubate, various trans-laryngeal techniques of ventilation can be used in emergency: jet ventilation via the trans crico-thyroid route, the use of a cricotomy cannula, or a minitracheotomy set. PMID- 2331085 TI - [Traumatic infarction of the right ventricle caused by coronary dissection]. AB - A case is reported of a 47 year-old man who suffered from a right ventricular myocardial infarct which occurred as a result of right coronary arterial dissection after non-penetrating anteroposterior chest compression. The patient was admitted with right heart failure and a central venous pressure of 17 cm H2O. The ST segment in leads V1 to V3 (V2: 7mm) was significantly elevated. Echocardiography showed dilatation of both right atrium and ventricle, with a deviated septum. Emergency cardiac angiography confirmed a hypokinetic right ventricle, with no other abnormal finding. Coronary angiography, performed 24 h after admission, revealed a dissection of the second part of the right coronary artery, with a normal left coronary system which reperfused that part of the right coronary arterial territory located beyond the dissection. The ST segment elevation stopped at the 10th hour. Initially, the patient's condition worsened. Thereafter, he slowly improved under treatment (5.5 micrograms.kg-1.min-1 dobutamine, and fluids so as to maintain a pulmonary wedged pressure of about 15 mmHg). As post-traumatic myocardial infarction is rare, the diagnostic and therapeutic strategies are discussed. PMID- 2331086 TI - [Right ventricular assistance using a centrifugal pump after heart transplantation]. AB - A case of right ventricular assistance required after emergency heart transplantation is reported. The patient was a 62 year-old man with terminal congestive heart failure due to ischaemic cardiomyopathy. Preoperatively, this patient had a cardiac index of 1.93 1.min-1.m-2, moderate pulmonary hypertension (mean Ppa: 34 mmHg) and pulmonary arteriolar resistances at 440 dyn.s.cm-5; clinical examination revealed pulmonary oedema, cardiac liver and oliguria with renal failure. Cardio-pulmonary bypass lasted 145 min, including 50 min of assistance after graft reperfusion. Despite postoperative dopamine and dobutamine treatment, oliguria and central venous pressure increased, and higher doses of catecholamines (adrenaline, noradrenaline) and pulmonary intraarterial prostaglandin E1 infusions were required. Despite these agents and haemofiltration, mechanical assistance was needed and a centrifugal pump set up. Diuresis and haemodynamic parameters improved. The patient was weaned from this assistance after 102 h. A satisfactory haemodynamic status was then maintained, but still required 1.4 micrograms.kg-1.min-1 noradrenaline and 0.02 microgram.kg 1.min-1 prostaglandin E1. Six days later, the patient was weaned from the ventilator, but he rapidly developed fatal aspergillus septicaemia. This case demonstrates that temporary mechanical assistance can be useful for treating right ventricular failure occurring after transplantation. PMID- 2331087 TI - [Value of continuous venous blood oxygen measurement during external circulatory assistance]. AB - A case is reported of a 40 year-old man, on the waiting-list for heart transplantation, who developed terminal heart failure. Using an Opticath catheter and a radial artery catheter, SV(-)O2 was monitored continuously, and cardiac output, pulmonary arterial and wedged pressures, and right atrial pressure were repeatedly measured. Despite appropriate treatment (adrenaline, dobutamine, glyceryl trinitrate), the patient remained in anuria and cardiogenic shock. External circulatory support (ECS) (BVS 5000 Abiomed) was therefore used as a bridge to cardiac transplantation. The resultant increase in systemic blood flow led to an early and fast rise in SV(-)O2, from 40% to 73%, with a decrease in the oxygen extraction ratio (ERO2) from 50 to 30%. Serum lactate concentrations returned to normal within the first six hours of ECS (less than 120 mg.l-1). During the first 24 h of ECS, SV(-)O2 decreased and ERO2 rose significantly on two occasions: during an episode of shivering, and another of restlessness during nursing. An attempt at weaning the patient from the ventilator at the 39th h also led to a sudden decrease in SV(-)O2, with a rise in ERO2. The Opticath catheter was finally removed after 150 h of ECS because of a decrease in reflected light intensity. PMID- 2331089 TI - [Transient block of the brachial plexus after catheterization of the subclavian vein]. AB - Two cases are reported of brachial plexus anaesthesia and palsy after catheterization of the subclavian vein. This very rare complication occurred after several unsuccessful attempts to catheterize one or both subclavian veins. This was due to inexperience, with insufficient knowledge of clinical anatomy, infiltration with unnecessarily high doses of local anaesthetic, and accidental puncture of the brachial plexus by an infraclavicular approach. One of the patients also had iatrogenic pneumothorax. PMID- 2331088 TI - [Worsening of chronic disseminated intravascular coagulation after embolization of the renal artery]. AB - A case is reported of a 60 year-old patient with chronic disseminated intravascular coagulation (DIC) which was increased by the therapeutic embolization of a renal tumour. The patient had 2 primary carcinomas (renal and prostatic) with vertebral metastases, severe chronic anaemia (due to haematuria), and chronic DIC, with thrombocytopaenia, soluble complexes, and fibrinogen and fibrin degradation products. Therapeutic embolization of the renal artery was carried out with fragments of dura mater. Although the result was anatomically very satisfactory, the patient's condition worsened, with continuing haematuria, and development of an haematoma in the lumbar fossa. Coagulation factors and antithrombin III (AT III) concentrations decreased, whereas the activated partial thromboplastin, thrombin and reptilase times increased. The patient also suffered from acute renal failure (creatinine: 690 mumol.l-1). Treatment consisted in fluid replacement, red blood cell and platelet transfusions, 150 IU.kg-1.d-1 heparin and 20 IU.kg-1.d-1 AT III. Haematological tests returned to pre embolization values on the ninth day. The sudden worsening in the patient's condition was probably due to the sudden massive release of tissue thromboplastins related to the renal necrosis induced by the therapeutic embolization. The use of heparin AT III in the management of this patient is discussed. PMID- 2331090 TI - [A device for monitoring respiration during anesthesia: the para-tracheal monitor]. AB - The paratracheal audible respiratory monitor (PTARM) was assessed in anaesthetized patients who were not intubated. Its working principle is simple: the sound generated by the passage of air between the vocal cords is picked up by a microphone placed on the patient's neck; the electronic signal is then amplified and changed into an audible one. It can also be recorded. This monitor was compared to others already available, Transcor, which monitors breathing sounds using a stethoscope as transducer, and Thermistor, which monitors the changes in air temperature due to air movement during breathing. The PTARM does not tie the anaesthetist down to the patient's bed, as do the precordial or oesophageal stethoscopes. Its usefulness in detecting aspiration is under investigation. It is a reliable, noninvasive and cheap breath-to-breath respiratory monitor, which can also be used in intubated patients. PMID- 2331091 TI - Clinically significant radiograph misinterpretations at an emergency medicine residency program. AB - Radiographic misinterpretation rates have been suggested as a quality assurance tool for assessing emergency departments and individual physicians, but have not been defined for emergency medicine residency programs. A study was conducted to define misinterpretation rates for an emergency medicine residency program, compare misinterpretation rates among various radiographic studies, and determine differences with respect to level of training. A total of 12,395 radiographic studies interpreted by emergency physicians during a consecutive 12-month period were entered into a computerized data base as part of our quality assurance program. The radiologist's interpretation was defined as correct. Clinical significance of all discrepancies was determined prospectively by ED faculty. Four hundred seventy-five (3.4%) total errors and 350 (2.8%) clinically significant errors were found. There was a difference in clinically significant misinterpretation rates among the seven most frequently obtained radiograph studies (P less than .0005, chi 2), accounted for by the 9% misinterpretation rates for facial films. No difference (P = .421) was noted among full-time, part time, third-year, second-year, and "other" physicians. This finding is likely due to faculty review of residents' readings. Evaluation of misinterpretation rates as a quality assurance tool is necessary to determine the role of radiographic quality assurance in emergency medicine resident training. Educational activities should be directed toward radiographic studies with higher-than-average reported misinterpretation rates. PMID- 2331092 TI - The value of alkaline phosphatase in peritoneal lavage. AB - The accuracy of peritoneal lavage for diagnosis of intra-abdominal injury in trauma is limited by its relative lack of sensitivity for hollow viscus injury. Peritoneal lavage in the dog indicates that alkaline phosphatase is an early marker of intestinal injury. If these results were confirmed in human patients, alkaline phosphatase determination would improve lavage sensitivity for hollow viscus injuries. A study was conducted to determine the usefulness of alkaline phosphatase in lavage in human beings. Alkaline phosphatase was measured in all trauma lavage samples sent for laboratory assay during a one-year period. Two hundred ninety-two lavages were performed: 25 were positive by laboratory criteria, and 66 were grossly positive. There were 13 intestinal injuries--nine were grossly positive, and four were diagnosed by laboratory results. Three of these four patients with intestinal injuries had elevated lavage alkaline phosphatase. All three (lavaged from 30 minutes to two hours after injury) also had elevated white blood cells or bile in the lavage fluid. The remaining intestinal injury was diagnosed by lavage bile but had no elevation of alkaline phosphatase (lavaged 15 minutes after injury). Two patients with elevated alkaline phosphatase in otherwise negative lavages were observed for at least five days; neither demonstrated any evidence of intra-abdominal injury. We conclude that alkaline phosphatase is no better than traditional determinants of intestinal injury in peritoneal lavage. In no patient was alkaline phosphatase helpful in diagnosing a hollow viscus injury, and its use would have prompted two unnecessary laparotomies. These data do not support the use of lavage alkaline phosphatase to identify hollow viscus injuries. PMID- 2331093 TI - Nasotracheal intubation using a flexible lighted stylet. AB - Nasotracheal intubation is an essential skill for clinicians involved in the care of acutely ill or injured patients. Unfortunately, it has the dangers and difficulties of any blind technique. Although usually performed in the awake patient, nasotracheal intubation has also been used in the apneic patient. Transillumination of the soft tissues of the neck with a lighted stylet has been shown to be a reliable method of orotracheal intubation. The usefulness of a longer, flexible lighted stylet as an aid to nasotracheal intubation in the apneic patient has been examined. Eighty patients, who were paralyzed, apneic, and about to undergo nasotracheal intubation for elective ear, nose, and throat or maxillofacial surgery were randomized to be nasotracheally intubated blindly or with a stylet by an emergency medicine resident or anesthesiologist. Sixty three percent intubated in the lighted-stylet group and 41% in the blind nasotracheal intubation group were successfully intubated. There were no significant differences in the time needed to intubate or the number of attempts. There were notable differences in the success rates of individual intubators with each technique. Although not statistically significant, our results suggest a useful role for the lighted stylet in nasotracheal intubation in the apneic patient. PMID- 2331094 TI - Oral intubation in the multiply injured patient: the risk of exacerbating spinal cord damage. AB - The use of oral intubation during the resuscitation of seriously injured patients has been discouraged because of the fear that this technique may lead to cervical cord damage. We report a retrospective study of the 18-month experience of an emergency department in which oral intubation was the usual method of airway control for victims of blunt trauma. There were 237 injured patients intubated in the ED; 21 patients (8.9%) had cervical cord or bone injury. There were no patients in whom a neurologic loss followed an airway maneuver. Oral intubation was the definitive airway maneuver in 213 patients. There was no statistically significant difference in the type of definitive airway maneuver used (eg, oral intubation, nasal intubation, or cricothyrotomy-tracheotomy) between patients with cervical injuries and patients without such injuries. The risk of spinal cord injury secondary to oral intubation in the seriously injured patient was low in our population. Selection of the method for definitive airway control should be based primarily on the operator's skills and experience rather than the fear of inflicting cervical cord damage. PMID- 2331095 TI - TAC use and absorption of cocaine in a pediatric emergency department. AB - The topical anesthetic TAC (tetracaine 0.5%, adrenaline 0.05%, cocaine 11.8%) has been reported to be effective in pain control for local procedures. However, it has the potential for cocaine toxicity by absorption through an open wound. A study was undertaken to assess the systemic absorption of cocaine and its metabolites when TAC is used as a local anesthetic. Fifty-one children, 1 to 14 years of age, were enrolled in the study. Plasma for cocaine and/or its metabolite levels was available from 46 children and obtained 20 to 40 minutes after the topical anesthetic was applied. No plasma sample had detectable parent cocaine levels; however, 26 (56.5%) had cocaine metabolite levels. Ecgonine methylester levels were detected in plasma from six children and ranged from 59 to 985 ng/mL. Benzoylecgonine levels were detected in none of 19 specimens not preserved with sodium fluoride, and in 23 of 27 specimens to which sodium fluoride had been added. Benzoylecgonine levels ranged from 40 to more than 600 ng/mL. No clinical sign of cocaine toxicity was observed in any child. PMID- 2331096 TI - Hanging leg weight--a rapid technique for estimating total body weight in pediatric resuscitation. AB - The accuracy of two methods of rapidly estimating total body weight in children was assessed. The first method correlated patient length to known total body weight, and the second correlated the weight of both legs weighted together to known total body weight. One hundred children undergoing general anesthesia in the operating rooms of Childrens Hospital of Los Angeles were entered into the study. Each child had a known preoperative body weight. After induction of anesthesia, each child's supine length was measured and hanging (inert) legs were weighted. There was excellent linear correlation between hanging leg weight and total body weight (correlation coefficient [r2], 0.95) for all patients, and good linear correlation between supine length and total body weight, r2, 0.86). Range restriction analysis for both techniques showed poor correlation for total body weights of less than 10 kg and poor correlation for the supine length technique when total body weight was more than 25 kg. The hanging leg weight of an inert child has excellent correlation to total body weight for children weighing more than 10 kg. PMID- 2331097 TI - Pediatric emergency medicine--current standards of care: results of a national survey. AB - To assess current standards of care in pediatric emergency medicine, a questionnaire was mailed in May 1988 to the medical directors of all existing pediatric emergency medicine fellowship programs. Twenty-three programs (96%) completed this survey, which consisted of questions regarding census, staffing patterns, ancillary services, patient follow-up, and various clinical issues. The major deficiencies in pediatric emergency care identified by this survey concerned patient waiting time, weekend radiology coverage, patient follow-up, feedback to referring physicians, and feedback to emergency department housestaff on hospitalized patients. The data suggest that pediatric EDs associated with fellowship training programs are improving their quality of care, yet room for advancement in many categories remains. PMID- 2331098 TI - The role of the emergency physician in providing pediatric emergency care--a membership survey. AB - A survey of the membership of the American College of Emergency Physicians (ACEP) was undertaken to identify members with special interest or expertise in pediatric emergency medicine. A questionnaire was published in the August 1988 issue of ACEP News, which was distributed to 12,079 members. One hundred seventy one responses were returned, revealing a subset of the membership (1.42%) with a special interest or expertise in pediatric emergency care. This group was characterized as to type of residency training, board certification (completed or planned), practice location, and percentage of practice composed of children. Opinions were sought regarding subspecialty certification, continuing medical education needs, and quality and quantity of pediatric emergency medical training in pediatric and emergency medicine residency programs. More than 200 physicians were identified as resources in pediatric emergency medicine for ACEP. The majority of the respondents favored subspecialty board certification. Continuing education needs are generally being met, but there is a need for better geographical distribution of courses. Minifellowships and more pediatric rotations for emergency medicine residents were suggested. PMID- 2331099 TI - Characteristics of midsized urban EMS systems. AB - Emergency medical services (EMS) systems in 25 midsized cities (population, 400,000 to 900,000) are described. Information describing EMS system configuration and performance was collected by written and telephone surveys with follow-ups. Responding cities provide either one- or two-tier systems. In a one tier system, an advanced life support (ALS) unit responds to and transports all patients who use 911 to activate the system. Three types of two-tier systems are identified. In system A, ALS units respond to all calls. Once on scene, an ALS unit can turn a patient over to a basic life support (BLS) unit for transport. In system B, ALS units do not respond to all calls; BLS units may be sent for noncritical calls. In system C, a nontransport ALS unit is dispatched with a transporting BLS unit. For ALS calls, ALS personnel join BLS personnel for transport. Overall, cities staff an average of one ambulance per 51,223 population. One-tier systems average one ambulance per 53,291 compared with two tier systems, which average one ambulance per 47,546. In the two-tiered system B, the average ALS unit serves 118,956 population. In the 60% of cities that use a one-tier system, one ALS unit serves 58,336 (P less than .0005). Overall, the code 3 response time for all cities is an average of 6.6 minutes. The average response time of two-tier systems is 5.9 minutes versus 7.0 minutes for one-tier systems (.05 less than P less than .1). These data suggest that the two-tiered system B allows for a given number of ALS units to serve a much larger population while maintaining a rapid code 3 response time. PMID- 2331100 TI - Medicolegal documentation of prehospital triage. AB - Patients evaluated by paramedics but not transported to the hospital account for 50% to 90% of emergency medical services lawsuits. We reviewed 2,698 consecutive paramedic run reports to examine documentation in these cases. Documentation criteria for prehospital patient release were history, physical examination, vital signs, mental status, lack of significant mental impairment, and for patients refusing care, that risks of refusing were understood. Criteria for appropriate release were met in 65.2% of cases. Criteria omitted in inappropriate releases were risks of refusing care in 481 (51.3% of inappropriate releases), vitals in 320 (34.1%), mental status in 188 (20.0%), lack of impairment in 120 (12.8%), and history or physical in 19 (2.0%) cases. Age from 0 to 14 and 65 or more years and prehospital assessment of hyperventilation, psychiatric emergency, choking, infection, and patient deceased were significantly associated with appropriate release. Age from 35 to 54 years and prehospital diagnosis of no injury, head injury, seizure, minor trauma, and ethanol use were significantly associated with inappropriate releases. There was no association of appropriate release or inappropriate release with patient sex, contact with medical control, length of encounter, or time of day. Only one patient complication was believed due to inappropriate triage; this could be improved by implementation of standardized criteria. PMID- 2331101 TI - A review of prehospital care litigation in a large metropolitan EMS system. AB - A retrospective review of all claims brought against a large, metropolitan emergency medical services (EMS) system related to paramedic-patient encounters during the 12-year period from 1976 through 1987 was undertaken to review and describe the incidence and types of malpractice claims. During this period, EMS units responded to approximately 2 million calls and transported more than 1 million patients. Sixty claims occurred during the incidence study period (1976 through 1985). The overall litigation rate was one lawsuit per 27,371 paramedic patient encounters and one lawsuit per 17,995 patient transports. While the total number of runs and transports did not change significantly during the study period, the data indicate a trend of increasing claims filed against the prehospital care provider. To date, 26 cases (38%) have been settled with the majority involving either no monetary awards or nominal out-of-court settlements. PMID- 2331102 TI - Congenital diaphragmatic hernia presenting as massive gastrothorax. AB - Delayed herniation of abdominal contents through a congenital diaphragmatic hernia may occur beyond the neonatal period. The case of a 29-month-old child with a Bochdalek hernia presenting as acute respiratory failure is presented. Chest radiography showed a tension gastrothorax that was misread as a tension pneumothorax. Tube thoracostomy resulted in clinical improvement by perforating and decompressing the stomach. Nasogastric tube placement confirmed herniation of the stomach into the left chest and is the initial treatment of choice when a tension gastrothorax is identified. A congenital diaphragmatic hernia must be recognized promptly so that rapid gastric decompression and surgical repair of the diaphragmatic defect can be performed. PMID- 2331103 TI - Transient atrial fibrillation precipitated by hypoglycemia. AB - Two noninsulin-dependent diabetic patients developed transient atrial fibrillation precipitated by hypoglycemia that reverted to sinus rhythm after administration of IV dextrose. Atrial fibrillation as a complication of hypoglycemia in diabetic patients has been reported in only two patients with insulin-dependent diabetes mellitus. PMID- 2331104 TI - Odontogenic cervical necrotizing fasciitis. AB - Necrotizing fasciitis is a severe soft-tissue infection characterized by diffuse necrosis of fascia and subcutaneous tissue; initially, skin and muscle are usually spared. The trunk, abdomen, perineum, and extremities are the most commonly involved areas. The case of a 55-year-old man with a cervical necrotizing fasciitis from an infected tooth is presented. The medical history, etiology, anatomy, precipitating factors, clinical presentation, and therapy of this infection are discussed. Early recognition allows effective therapy with aggressive surgical intervention, broad-spectrum antibiotics, and supportive care. Misdiagnosis (eg, as cellulitis) and delayed surgical treatment can result in severe systemic toxicity and a mortality rate that approaches 40%. PMID- 2331105 TI - The enlarging clinical spectrum of Lyme disease: Lyme cerebral vasculitis, a new disease entity. AB - The case of a patient with cerebral vasculitis with a right thalamic infarct associated with cerebral spinal fluid Lyme disease is presented. This entity has not been described in the United States, and only one similar case in the world literature could be found. The patient presented with a progressive headache and subsequent development of grand mal seizure activity. Lyme disease has been associated with cranial nerve palsies, peripheral and cranial radiculopathies, aseptic meningitis, encephalitic symptoms, chorea, and demyelinating polyneuropathy presenting like Guillain-Barre syndrome. These syndromes can occur separately or in combination. Stroke and strokelike syndromes have been attributed to Lyme disease. The literature concerning the neurologic manifestations of Lyme disease is reviewed. PMID- 2331106 TI - The ability of physicians to predict electrolyte deficiency from the ECG. AB - The ECG is considered to be a fairly accurate reflection of a patient's electrolyte status. Two full-time academic emergency physicians, each board certified in two specialties, interpreted the ECGs of 97 consecutive alcoholic patients presenting to the emergency department. Serum potassium, calcium, and magnesium values were obtained on all patients within one hour of ECG performance. The physicians attempted to predict abnormalities of serum electrolytes from the ECG tracing alone when blinded to all laboratory values, the clinical situation, and each other's readings. The combined results of both readers yielded a sensitivity of .74 and a specificity of only .29. The positive predictive value of the ECG in predicting electrolyte deficiency was .41 and the negative predictive value was .63. Electrolyte disturbances cannot be accurately predicted from an ECG even in high-risk patients. Serum electrolyte determinations remain the most effective method of screening for these deficiencies. PMID- 2331107 TI - Introduction to biostatistics: Part 3, Sensitivity, specificity, predictive value, and hypothesis testing. AB - Diagnostic tests guide physicians in assessment of clinical disease states, just as statistical tests guide scientists in the testing of scientific hypotheses. Sensitivity and specificity are properties of diagnostic tests and are not predictive of disease in individual patients. Positive and negative predictive values are predictive of disease in patients and are dependent on both the diagnostic test used and the prevalence of disease in the population studied. These concepts are best illustrated by study of a two by two table of possible outcomes of testing, which shows that diagnostic tests may lead to correct or erroneous clinical conclusions. In a similar manner, hypothesis testing may or may not yield correct conclusions. A two by two table of possible outcomes shows that two types of errors in hypothesis testing are possible. One can falsely conclude that a significant difference exists between groups (type I error). The probability of a type I error is alpha. One can falsely conclude that no difference exists between groups (type II error). The probability of a type II error is beta. The consequence and probability of these errors depend on the nature of the research study. Statistical power indicates the ability of a research study to detect a significant difference between populations, when a significant difference truly exists. Power equals 1-beta. Because hypothesis testing yields "yes" or "no" answers, confidence intervals can be calculated to complement the results of hypothesis testing. Finally, just as some abnormal laboratory values can be ignored clinically, some statistical differences may not be relevant clinically. PMID- 2331108 TI - Medical staff responsibilities for emergency department patients requiring urgent medical attention. American College of Emergency Physicians. PMID- 2331109 TI - Writing admission orders. American College of Emergency Physicians. PMID- 2331110 TI - Providing telephone advice from the emergency department. American College of Emergency Physicians. PMID- 2331111 TI - Telephone orders in the emergency department. American College of Emergency Physicians. PMID- 2331112 TI - The safety of orotracheal intubation in patients with suspected cervical-spine injury. PMID- 2331113 TI - Abstracts of the 3rd International Conference on Emergency Medicine. Toronto, Ontario, Canada, June 24-29. PMID- 2331114 TI - The past & future of academic emergency medicine. PMID- 2331115 TI - Benefits of early defibrillation. PMID- 2331116 TI - Data collection & observer bias. PMID- 2331117 TI - Lung function compromised by spinal immobilization. PMID- 2331118 TI - Supine exercise electrocardiography compared with exercise radionuclide angiography in noninvasive identification of severe coronary artery disease. AB - STUDY OBJECTIVE: To determine the incremental value of exercise radionuclide angiography for identification of severe coronary artery disease. DESIGN: Retrospective analysis comparing logistic regression models. SETTING: A tertiary care referral center. PATIENTS: Three hundred and ninety-one consecutive patients who had normal resting electrocardiograms (ECGs) and no digoxin therapy within the previous week. MEASUREMENTS AND MAIN RESULTS: The exercise ECG model, consisting of magnitude of ST depression, exercise heart rate, and patient gender, was highly predictive of three vessel or left main coronary artery disease (chi 2 = 100, P less than 0.0001). The model correctly classified 60% of the study group which included 56 patients with and 179 without severe disease. The addition of radionuclide angiographic variables improved the predictive power of the model (chi 2 = 124, P less than 0.0001). However, the exercise radionuclide angiographic variables increased the number of patients who were correctly classified by only 11 and the percentage by 3% (to a total of 63% of the study group). CONCLUSIONS: The modest additional advantage provided by exercise radionuclide angiography for identification of three vessel or left main coronary artery disease in patients with normal resting ECGs would not appear to justify its routine use for this purpose. Before this conclusion is used as a guide for clinical practice, our results should be prospectively confirmed in a separate sample of patients in another institution. PMID- 2331119 TI - Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia. AB - STUDY OBJECTIVE: To determine the effect of previous aerosolized pentamidine therapy on diagnosis and presentation of Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: A tertiary care hospital. PATIENTS: Fifty-two consecutive patients with P. carinii pneumonia and underlying infection with the human immunodeficiency virus (HIV) who had bronchoscopy. Twenty-one patients who were on aerosolized pentamidine therapy served as the study group. Thirty-one patients who had not received the drug served as the control group. MEASUREMENTS AND MAIN RESULTS: The yield of bronchoalveolar lavage for P. carinii pneumonia was 62% for the study group and 100% for the control group (P less than 0.05). This lower yield was significant for the subset of patients having their first episode of P. carinii pneumonia. The yield of transbronchial biopsy was similar for both groups of patients (81% compared with 84%). The yield of bronchoscopy was not influenced by use of zidovudine. Review of lavage specimen slides suggested that there may be fewer organisms present in patients receiving aerosolized pentamidine. An atypical roentgenographic presentation of upper lobe predominant infiltrates was seen in 38% of the study patients and 7% of the control patients. In addition, pneumothoraces and cystic changes were also frequently seen in the study patients. Gallium scans, when done, were also atypical in the study group. Markers of the severity of disease, however, were similar in both groups. CONCLUSION: The yield of bronchoalveolar lavage for P. carinii pneumonia in HIV-infected patients is lower in patients receiving aerosolized pentamidine. Unusual roentgenographic presentations and atypical gallium scans are also found in this setting. PMID- 2331120 TI - L-tryptophan ingestion associated with eosinophilic fasciitis but not progressive systemic sclerosis. AB - OBJECTIVE: To assess the use of L-tryptophan by patients with eosinophilic fasciitis and compare this with its use by patients with progressive systemic sclerosis (scleroderma). DESIGN: Retrospective and prospective analysis. Six patients with eosinophilic fasciitis were identified retrospectively and two prospectively. Retrospective identification of patients was done by questioning hospital-affiliated rheumatologists and dermatologists and by searching the hospital dermatopathology database. The patients with scleroderma or morphea were prospectively identified by questioning consecutive office patients with these established diagnoses. SETTING: University of Pennsylvania rheumatology and dermatology practices. PATIENTS: Eight patients with eosinophilic fasciitis; 40 consecutive patients with scleroderma (27 with diffuse cutaneous and 13, limited cutaneous disease); 3 patients with morphea. RESULTS OF DATA ANALYSIS: All eight patients with eosinophilic fasciitis had taken L-tryptophan before the onset of their disease. All had myalgias and high peripheral eosinophil counts (most greater than 5000 cells/mm3). Only 1 of 40 patients with scleroderma (no patients with morphea) had used L-tryptophan preceding illness (P less than 0.001 compared with eosinophilic fasciitis). Six patients with eosinophilic fasciitis had taken L-tryptophan for less than 8 months. One patient had taken it for 9 years before developing skin induration. Two patients were newly identified as having hypothyroidism; two developed neuropathy; and two had severe flexion contractures (several occurring in areas without skin induration). Five patients had low-titer antinuclear antibodies, indicating a possible autoimmune process. Most patients had only a partial response to systemic corticosteroid therapy. One patient has had important disease regression in response to isotretenoin therapy that was evident even while she continued to take L-tryptophan. CONCLUSIONS: L-Tryptophan use can lead to eosinophilic fasciitis whereas it does not appear to cause classic scleroderma. The disease process does not automatically remit after discontinuation of L-tryptophan-containing products. PMID- 2331121 TI - Preoperative pulmonary function testing. American College of Physicians. PMID- 2331122 TI - The carpal tunnel syndrome in cardiologists. PMID- 2331123 TI - Topical clonidine and diabetic gastroparesis. PMID- 2331124 TI - Median incubation time for human immunodeficiency virus (HIV) PMID- 2331125 TI - Ocular amyloidosis: clinical points learned from one case. AB - The etiology of bilateral vitreous opacification in a 72-year-old man was undiagnosed until after a second vitrectomy when the aspirate was tested with Congo red and found to stain for amyloid. Failure to recognize the significance of a mild peripheral neuropathy delayed the diagnosis. Visual acuity OU remained 20/40 for one year after completion of multiple ocular surgeries. Experience from this case suggests that amyloidosis should be considered in all patients with unexplained vitreous infiltration. A conjunctival biopsy may be helpful diagnostically, and removal of as much cortical and retrolental vitreous as is safe may reduce the incidence of reopacification. PMID- 2331126 TI - Unilateral corneal intraepithelial neoplasia: management of the recurrent lesion. AB - Corneal intraepithelial neoplasia is an uncommon entity that may recur with potential for local invasive growth. Disease severity ranges from mild to severe dysplasia, the latter representing intraepithelial carcinoma in situ. Our case focuses on the importance of the neighboring bulbar conjunctiva in promoting recurrence of the corneal pathology. Over eight years, there were recurrences after debridement. After removal of grossly normal but histologically dysplastic bulbar conjunctival mucosa bordering the evident corneal process, successful control was achieved. There has been no recurrence for five years. PMID- 2331127 TI - Sclerosing syringoma. AB - Syringoma, a benign sweat gland tumor which may occur in the eyelid, commonly presents as multiple lesions in young women. We had an unusual case of a sclerosing syringoma found as a single lesion in the lower eyelid of a man. PMID- 2331128 TI - Bilateral altitudinal visual fields. AB - We describe two patients with absolute, complete, binocular inferior altitudinal hemianopias. These altitudinal visual-field defects (AVFDs) involved both nasal and adjacent temporal quadrants and respected the horizontal meridian. The reported conditions and locations in the visual system that cause "conventional" AVFDs and their bilateral occurrence are reviewed. Division of the visual system into altitudinal halves results from the topographic arrangement of nerve fibers and their blood supply in the retina, optic nerves, and visual cortex. Lesions at these locations resulting in AVFDs are usually due to vascular occlusion or may result from a penetrating missile injury to the superior occipital lobes. It is important to emphasize that the nerve fiber layer of the retina respects the horizontal meridian only in the nasal field, not in the temporal field; therefore incomplete AVFD is more common. Because of the anastomotic blood supply of the occipital pole, only AVFDs due to occipital infarcts spare fixation. Diagnosis of retinal branch artery occlusion or anterior ischemic optic neuropathy is aided by the presence of a unilateral AVFD along with ipsilateral funduscopic abnormalities and, in most bilateral examples, by its sequential temporal development. Bilateral occipital infarcts, as in our two cases, are characterized by sudden, simultaneous onset of AVFDs, an absence of retinal, retinovascular, or optic nerve abnormality and confirmation by computed tomographic scanning. PMID- 2331129 TI - Normal gray scale displays in the presence of arcuate scotomas in automated threshold perimetry. AB - In 2.4% of visual fields and 10.4% of eyes with well-established early glaucoma, a normal gray-scale display was present despite an arcuate scotoma on pattern deviation display in the same central threshold visual-field printout (30-2 single-field analysis program, Humphrey Field Analyzer). Also, the pattern deviation probability plot highlighted the presence and significance of the arcuate scotoma. To my knowledge these findings have not been previously reported in the literature. In suspected glaucoma or early glaucoma, visual-field analysis based on the gray-scale display alone can be misinterpreted. In this population, the defect-depth or pattern-deviation displays should be examined before any diagnostic or therapeutic decision is made. PMID- 2331130 TI - Low-intensity grids improve sensitivity of amsler grid testing in diabetic patients without background retinopathy. AB - We tested 22 eyes of 12 diabetic patients without retinopathy for visual loss using four types of Amsler grids. The Amsler grids, in order of decreasing intensity, were the standard white, bright red, fine red, and threshold (through cross-polarizing filters). The threshold grid detected the largest number of scotomas--16 versus 12, seven, and seven, respectively--and the largest total area of all scotomas--1594 degrees 2 of arc versus 1237, 994, and 927, respectively. In addition, metamorphopsia lessened as grid intensity decreased. These results demonstrate that the sensitivity of Amsler grid testing for visual loss in diabetics without retinopathy improves by decreasing the intensity of the grid used. PMID- 2331131 TI - [Anterior interventricular revascularization using the internal mammary artery. Short and medium-term follow-up of 140 patients]. AB - Between February 1983 and June 1987, 140 patients underwent surgery for anterior interventricular revascularization using the left internal mammary artery (the right had been used once). Operative mortality was 3.5%, but this value decreased to 2.2% when the familiarization period for the technique was taken into account. 112 patients were monitored for at least 11 months, and 85 of these accepted an angiographic examination at the end of the follow-up period. No graft was occluded. Only two were thin due to an inadequate stenosis of the anterior interventricular septum. One graft was 90% stenosed at its anastomosis. Moderate competitive flux was noted in five cases. These results are in agreement with published findings, and comparison with literature reports confirms that the internal mammary artery is superior to the saphenous vein as graft material. PMID- 2331132 TI - [The hospital course of thrombolyzed myocardial infarction: role of bypass and angioplasty]. AB - The frequency of indications for revascularization (bypass and angioplasty) after intravenous thrombolysis in myocardial infarction (MI) varies from 3.3% (Gissi) to 60% (Tami). Initial progress in 30 patients hospitalized consecutively for MI treated by thrombolysis (group A) was compared with that of 30 MI patients treated conventionally (group B) over the same period. There were no between group differences in age, sex, infarction history, bypass history, topography of infarction or extent of coronary lesions. Group A was characterized by a larger ejection fraction (51.7 +/- 9.2% vs 44.9 +/- 10%; p less than 0.05), a higher frequency of ischemic recidivism (33% vs 10%; p less than 0.05), and more frequent indications for secondary revascularization (50% vs 20%; p less than 0.02). PMID- 2331133 TI - [Conduction disorders in Cheyne-Stokes respiration caused by cardiac insufficiency]. AB - This report describes a case of Cheyne-Stokes respiration linked to heart failure, with periodic disturbances of atrioventricular conduction during the augmentation phase of the tidal volume. The circulatory retardation caused by heart failure induced a phase lag of the negative retroaction system and secondarily an oscillation in the respiratory command. The conduction disturbances resulted from vagal stimulation of multifactorial origin. The atrioventricular conduction disturbances were analogous to those seen in other periodic respiratory diseases. PMID- 2331134 TI - [MRI study of hypoplasia of the abdominal aorta in a 3-month-old infant]. AB - The authors report coarctation of the abdominal aorta in an infant aged three months. A complete study of the lesion was made by magnetic resonance imaging (MRI), which confirmed involvement of the renal and iliac arteries, dilatation of the celiac trunk and of the superior mesenteric artery, and the absence of visualization of the inferior mesenteric artery. MRI is seen to be a valuable tool for monitoring this type of anomaly and allows angiography to be avoided. PMID- 2331135 TI - Effect of prolonged galactose consumption on galactose tolerance in young healthy humans. AB - This study was carried out on two groups of healthy young subjects. One group (n = 8) was given a single oral dose of galactose (0.5 g/kg body weight), and a single measurement of blood galactose was made 40 min later. A second group (n = 16) was given a daily supplement of 0.5 g/kg galactose for 15 days, and blood galactose and galactitol were measured. On the first day of the test period, some subjects seemed to tolerate galactose less well than others: galactitol appeared in their plasmas and could be related to a significantly higher galactosaemia than that of subjects without detectable galactitol in the plasma. However, after 15 days of galactose intake, the less galactose-tolerant subjects appeared to have adapted, as indicated by the significant decrease in the blood galactose and the disappearance of galactitol. No change was found in the galactose-tolerant subjects. No significant difference was found between males and females. PMID- 2331136 TI - Chain elongation of fatty acids in rat small intestine: subcellular localization and effects of clofibrate and partially hydrogenated fish oil. AB - Clofibrate treatment was found to increase by a factor of two the activity of malonyl-CoA-dependent palmitic acid chain elongation in crude 'microsomal' fractions isolated from rat small intestine. A slight stimulation was indicated also after feeding a high fat diet containing partially hydrogenated fish oil (PHFO). This effect was, however, not statistically significant. Subcellular localization of this chain elongation activity was studied by Nycodenz gradient centrifugation. Chain elongation of palmitic acid was observed only in fractions containing high esterase activity, suggesting a microsomal localization. Similar distributions were seen after feeding the peroxisomal proliferators clofibrate and PHFO. Chain-shortening activity was found in the fractions containing high catalase activity, confirming our earlier studies suggesting a peroxisomal localization of this activity also in rat small intestine. PMID- 2331137 TI - Effect of undernutrition on the immune response to rotavirus infection in mice. AB - The effect of moderate and severe undernutrition on the immune response to EDIM rotavirus was studied in mice. A moderate state of undernutrition was produced by feeding weanling mice either 15 or 30% less diet than the control group had eaten on the previous day, for 7 weeks. After 6 weeks, mice were given 30 microliters/mouse of EDIM rotavirus orally and the antibody production was measured 1 week later. The delayed-type hypersensitivity (DTH) response to picryl chloride (PC) was measured as an index of cell-mediated immunity. For severe undernutrition, weanling mice were fed either 30 or 50% less diet than the control group had eaten on the previous day, for 12 weeks. After 11 weeks of feeding, animals were given 30 microliters/mouse of EDIM rotavirus either orally or intramuscularly and the antibody production was measured 1 week later. In moderate undernutrition, the serum antibody levels specific to rotavirus and the DTH response to PC were normal in all dietary groups compared with the control group. In severe undernutrition, the antibody levels following oral challenge of rotavirus were similar in all dietary groups. There was a significant impairment of serum antibody levels following intramuscular challenge in the group fed 50% less than the control group. It is concluded (1) that a balanced reduction in food intake does not impair the immune response, unless severe restriction is maintained for a long period of time, and (2) that the antibody response varies with the route of immunization. PMID- 2331138 TI - Effect of ascorbic acid supplementation on haematological response and ascorbic acid status of young female adults. AB - Haematological response and ascorbic acid (AA) status were evaluated in 32 young adult females (age 20-34 years) 8 weeks after supplementation with two levels of AA (50 and 100 mg). Both levels of AA intake produced a similar response marked by significant elevation (p less than 0.01) in Hb concentration, Hct level, RBC count, serum and leucocyte ascorbate concentrations. Ten weeks after withdrawal of the supplements, values for all parameters evaluated decreased significantly (p less than 0.01) to presupplementation levels. Haemoglobin concentration and leucocyte ascorbate remained relatively higher (p less than 0.01) than initial values in subjects who received 100 mg AA. This study showed that AA supplementation improved erythropoietic activity and AA status of our female population. However, the higher dose of AA (100 mg) sustained Hb concentration and tissue ascorbate longer after withdrawal of supplementation. PMID- 2331139 TI - Effect of sampling site on retinol, carotenoid, tocopherol, and tocotrienol concentration of adipose tissue of human breast with cancer. AB - The effect of sampling site and closeness of malignant tumor on the retinoid, carotenoid, tocopherol, and tocotrienol concentration of adipose tissue of human breast was studied in 10 cases of breast cancer. The four anatomic quadrants of breast did not differ from each other statistically significantly in relation to adipose tissue concentrations of the vitamins studied. Proximity of malignant tumor did not affect the vitamin concentrations when compared to the more distant sampling sites. Representative sample of breast adipose tissue for vitamin concentration analysis can be obtained from tissue adjacent to the tumor. PMID- 2331140 TI - Influence of kinetics of gastric emptying on hepatic IGF1 production in young calves. AB - Five preruminant calves, fitted with chronically indwelling catheters in the hepatic and portal veins and hepatic artery, were fed two kinds of diet (a conventional clotting milk diet and an incurdled milk diet) or fasted for 24 h. The statistical analysis of the plasma growth hormone (GH; nmol/l) or IGF1 (nmol/l) daily secretory profiles indicated that hormonal levels were very high in fed calves (GH mean values: 0.40 +/- 0.11 and 0.36 +/- 0.10, respectively; IGF1 mean values: 6.65 +/- 0.57 and 7.54 +/- 0.33, respectively). The GH secretory profile observed over a 24-hour period showed 7 secretory spikes without periodicity in both diets. In fasting animals, plasma GH and IGF1 concentrations were very low (0.17 +/- 0.08 and 3.08 +/- 0.36, respectively) and stable, they increased with refeeding (1.51 +/- 0.05 and 7.36 +/- 0.55, respectively). Hepatic IGF1 production (micrograms/kg body weight/day) was 195 +/ 7 in standard milk fed calves and -255 +/- 30 in others. Our results demonstrated that nutritional factors, such as different kinetics of gastric emptying or fasting, may influence hepatic IGF1 production in the conscious newborn calf. PMID- 2331141 TI - Possible role of thyroid hormone in decreased somatomedin-C levels in diabetic and starved rats. AB - To elucidate the possible role of thyroid hormone in somatomedin-C (SmC)/insulin like growth factor I regulation in diabetes mellitus and starvation, plasma SmC, liver SmC, and kidney SmC concentrations were measured in streptozotocin-induced (60 mg/kg) diabetic and starved (for 72 h) rats. Triiodothyronine (T3, 5.0 micrograms/kg every 24 h) was subcutaneously injected into diabetic rats for 7 days and into starved rats at 12, 36, and 60 h after starvation. Plasma T3, plasma SmC, liver SmC, and kidney SmC concentrations were significantly decreased in diabetic and starved rats. T3 administration restored plasma T3 levels to the normal value in diabetic and starved rats. Plasma SmC and kidney SmC concentrations were significantly increased in T3-treated starved rats, while they were not increased in T3-treated diabetic rats. These results suggest that thyroid hormone may have some role in SmC regulation during starvation, but may have no role in diabetes mellitus in the rat. PMID- 2331142 TI - Hexachlorobenzene uptake by fathead minnows and macroinvertebrates in recirculating sediment/water systems. AB - Fathead minnows (Pimephales promelas), the worm, Lumbriculus variegatus, and the amphipods Hyalella azteca and Gammarus lacustris were exposed to hexachlorobenzene (HCB) in water with and without a bed of HCB-spiked sediment. Water HCB concentrations were maintained by recirculation through HCB-packed columns. Recirculating HCB-bound particulates and possibly eroded HCB particulates were an added source of HCB in addition to the sediment bed. Significant bioaccumulation of HCB in animal tissues was observed in water-only and water-sediment exposures. The presence of the HCB-spiked sediment did not result in a significant increase in the uptake of HCB by the organisms, but there was a substantial increase in sediment HCB levels over time. Higher tissue HCB levels in aquaria without sediment suggest that the sediment was a more efficient sink for HCB than the organisms. PMID- 2331143 TI - Uptake of aromatic and chlorinated hydrocarbons by juvenile chinook salmon (Oncorhynchus tshawytscha) in an urban estuary. AB - A study was conducted to assess the potential for uptake of toxic chemicals by down-stream migrant salmon in an urban estuary. Juvenile chinook salmon (Oncorhynchus tshawytscha) were collected from the Duwamish Waterway (located in Seattle, Washington) and from the Nisqually River (a reference site). The mean concentrations of aromatic hydrocarbons and polychlorinated biphenyls (PCBs) in the stomach contents (food organisms) of salmon from the Duwamish Waterway were approximately 650 times and 4 times, respectively, higher than those in salmon from the Nisqually River. Similarly, the mean concentration of bile metabolites of aromatic compounds which fluoresce at benzo[a]pyrene wavelengths was 24 times higher in the urban salmon compared to the reference salmon, whereas the mean concentration of PCBs in liver of urban salmon was 3 times higher than that in reference salmon. The study clearly demonstrated that, during their residency in this urban estuary, juvenile chinook salmon bioaccumulate substantial levels of toxic chemicals. The possible effects of these chemical exposures on the health and survival of this species are not presently known. PMID- 2331144 TI - Environmental contaminant concentrations in biota from the lower Savannah River, Georgia and South Carolina. AB - Planned harbor expansion and industrial developments may adversely affect the economically important aquatic resources of the lower Savannah River, including those at the Savannah National Wildlife Refuge. To establish the present level of chemical contamination in this system, we collected a total of 102 samples of nine species of fish and fiddler crabs (Uca pugilator) from eleven sites in the lower Savannah River and on the Savannah National Wildlife Refuge, and analyzed them for concentrations of organochlorine chemicals, aliphatic and aromatic petroleum hydrocarbons, and 13 elemental contaminants: aluminum, arsenic, cadmium, chromium, cobalt, copper, iron, lead, manganese, mercury, nickel, selenium, and zinc. Residues of DDT (mainly as DDE), trans-nonachlor, dieldrin, Aroclor 1260, mirex, and petroleum hydrocarbons were common in fish from the lower Savannah River, but concentrations were below those warranting environmental concern. In general, the concentrations of elemental contaminants also were low; however, arsenic, cadmium, and chromium concentrations were elevated in fish from river stations near the city of Savannah, and lead was elevated in samples from the National Wildlife Refuge. Contamination of the lower Savannah River by organic and elemental contaminants, as indicated by concentrations in fishes and fiddler crabs, did not appear to pose a hazard. PMID- 2331145 TI - Measurement of manganese amelioration of cadmium toxicity in Chlorella pyrenoidosa using turbidostat culture. AB - Cadmium (Cd) toxicity and amelioration of Cd toxicity by Mn were measured in Chlorella pyrenoidosa, using turbidostat culture. The responses were measured in terms of the maximum specific growth rate, mu max, of the populations. In turbidostat culture mu max is a dependent variable that can be measured continuously. Cd (as CdCl2.2.5 H2O) was added to control populations at a concentration of 1.8 microM Cd. Toxicity was expressed after a 5 generation lag and resulted in a mu max steady state 62% lower than the initial control after 2 generations. With continued Cd exposure, Mn (as MnCl2.6H2O) was then added stepwise to a concentration of 10.4 microM Mn which caused a rapid, immediate increase in mu max followed by linear increase until a steady-state plateau was reached at a mu max 90% of control. The ameliorative response spanned 20 culture generations. After addition of Mn (10.4 microM), cellular Cd concentration did not change and cellular Mn concentration increased. Increase in mean cell size accompanied Cd exposure and was significantly decreased when supplemented with 10.4 microM Mn. Possible mechanisms of the amelioration are discussed. PMID- 2331146 TI - Influence of salinity and temperature on acute toxicity of cadmium to Mysidopsis bahia molenock. AB - Acute toxicity tests were conducted to compare estimates of toxicity, as modified by salinity and temperature, based on response surface techniques with those derived using conventional test methods, and to compare effect of a single episodic exposure to cadmium as a function of salinity with that of continuous exposure. Regression analysis indicated that mortality following continuous 96-hr exposure is related to linear and quadratic effects of salinity and cadmium at 20 degrees C, and to the linear and quadratic effects of cadmium only at 25 degrees C. LC50s decreased with increases in temperature and decreases in salinity. Based on the regression model developed, 96-hr LC50s ranged from 15.5 to 28.0 micrograms Cd/L at 10 and 30% salinities, respectively, at 25 degrees C; and from 47 to 85 micrograms Cd/L at these salinities at 20 degrees C. Trimmed Spearman Karber method used in analysis of a second data set yielded estimates at 20 degrees C and 25 degrees C comparable to those of multiple regression analysis. At 30 degrees C, the 96-hr LC50 was less than 11 micrograms/L. The relationship of median tolerance to cadmium concentration and exposure time was related to the interaction of both factors and independent of salinity between 10 and 30% at 25 degrees C. The quadratic model predicts mortality of 50% following exposures of less than 12 hr to the highest concentration examined (92 micrograms/L). For exposure durations of 16 and 24 hr, 50% mortality is predicted to occur at 78 and 56 micrograms/Cd/L, respectively. PMID- 2331147 TI - Fluoride accumulation and bone strength in wild black-crowned night-herons. AB - Fluoride was measured in femurs of black-crowned night-herons (Nycticorax nycticorax) living adjacent to a phosphate processing complex near Pocatello, Idaho. Fluoride (ash wt.) in femurs ranged from 540 micrograms/g to 11,000 micrograms/g and increased (P = 0.0001) with age, but with no difference (P = 0.80) between sexes. Adult males (greater than or equal to 4 years) contained 5,409 micrograms/g compared to 6,042 micrograms/g for adult females. The tibiotarsus (= tibiae in text) increased in diameter with age (P = 0.015) in this study; fluoride was nearly related (P = 0.065) to the increase. As the diameter increased with age, wall thickness decreased (P = 0.011) suggesting excessive internal bone resorption, but fluoride concentrations were not implicated in the relationship (p = 0.64). The apparent increase in diameter and decrease in wall thickness may have partially neutralized each other's effects on strength. Although significantly higher concentrations of fluoride were present in adults than in Third Year herons, no significant change in bone strength (maximum load or modulus of rupture) was detected between the two age classes, but three of the four comparisons showed adults with less strength (i.e., a hint of diminished strength with age). The tibiae of Hatch Year birds were significantly weaker than documented in older age classes, but incomplete growth was thought responsible. The strong relationship between age and fluoride concentrations reduced our ability to separate a "fluoride effect" from an "age effect." Other authors believed fluoride was responsible for an increase in bone diameter and the fluoride residues encountered in adults were within the range indicative of poisoning in cattle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331148 TI - Inhibitory effects of vanadium pentoxide on respiration of rat liver mitochondria. AB - The bioenergetic functions of liver mitochondria were studied following the acute and chronic exposure of rats to vanadium pentoxide via respiratory tract. The mitochondrial respiration with glutamate or succinate as substrate was inhibited significantly when compared to the control animals. No inhibition was found with ascorbate. The same effects were observed in vitro. Vanadium (V) was responsible for these inhibitory effects. It is postulated that significant amounts of vanadate are accumulated in the intermembrane space of liver mitochondria of the exposed rats. The process of "detoxification" by reduction of vanadate in the tissue may be insufficient to prevent the deleterious action of this compound on liver mitochondria. PMID- 2331150 TI - Chromatographic determination of dicofol and metabolites in egg yolks. AB - Egg yolk was spiked with p,p'-dicofol (p,p'-DCF) (0.1-2.0 micrograms/gm), p,p' dichlorobenzophenone (p,p'-DCBP) (0.1-2.0 micrograms/gm), and 1,1-bis(4 chlorophenyl)-2,2-dichloroethylene (p,p'-DDE) (0.05-1.0 micrograms/gm). The fortified egg yolk (2-5 g) was mixed with acetonitrile to extract non-fat organic materials. After removal of acetonitrile, the spiked chemicals were separated with a column chromatograph packed with acid alumina. Recovery efficiencies for p,p'-DCBP and p,p'-DDE were determined by gas chromatography, and for p,p' dicofol by high performance liquid chromatography. The recovery efficiencies for p,p'-dicofol, p,p'-DCBP and p,p'-DDE were 77.2-93.8%, 84.1-101.1%, and 88.5 96.0%, respectively. PMID- 2331149 TI - Effect of 1,1-dimethylhydrazine on lymphoproliferation and interleukin 2 immunoregulatory function. AB - The studies reported here suggest that the immunomodulatory effects of 1,1 dimethylhydrazine (UDMH) are associated, in part, with interference with interleukin 2 (IL-2) regulatory action. Concanavalin A (Con A)-stimulated DNA synthesis in murine splenocytes was inhibited from 18.6 to 44.1% at sub-toxic concentrations of UDMH (10 to 50 micrograms/ml) and IL-2-dependent DNA synthesis in CTLL-20 cells was inhibited from 11.3 to 41.58% at sub-toxic concentrations of UDMH (10 to 50 micrograms/ml). In addition, UDMH suppressed phorbol myristic acetate (PMA)-stimulated IL-2 production in EL-4 cells by up to 30% and slightly suppressed IL-2 production by Con A-stimulated murine splenocytes. In all cases, inhibition was evident at sub-toxic UDMH concentrations and was demonstrated to be independent of inactivation of IL-2 or interference with IL-2 absorption. It is suggested that UDMH has the potential to modify immune function through interference with IL-2 production and especially the lymphoproliferative response to IL-2. PMID- 2331151 TI - Short-term toxic effects of 1-naphthol on the digestive gland-gonad complex of the marine prosobranch Littorina littorea (L): a light microscopic study. AB - The short-term toxic effects of both sublethal and lethal concentrations of 1 naphthol were studied by light microscopy examination of the digestive gland gonad complex of the common periwinkle Littorina littorea. Exposure to naphthol produced severe tissue alterations characterized by disruption of digestive cells and presence of a high number of basophilic cells in the digestive tubules and infiltration of digestive, connective and gonadal tissues by hemocytes. Morphologically, the infiltrating hemocytes comprised of hemocytes with a small nucleus and eosinophilic cytoplasm, and hemocytes with a large nucleus and scarce cytoplasm. In addition, breakdown of ripe ova and resorption of gametes occurred, even at the sublethal concentration of 2.075 mg/L of naphthol, apparently related to phagocytosis by hemocytes. Differences in the hemocytic infiltration incidence were observed between male and female individuals, suggesting a different sensitivity to the experimentally induced stress condition between the two sexes. PMID- 2331152 TI - Biological and physical factors affecting the body burden of organic contaminants in freshwater mussels. AB - Biological and physical factors affecting the body burdens of hexachlorobenzene, octachlorostyrene, and four polychlorobiphenyl (PCB) congeners in freshwater mussels from Lake St. Clair, Ontario, Canada were investigated. Specimens of Lampsilis radiata (Barnes) and the non-native Elliptio complanata (Lightfoot) were deployed for forty days at four Lake St. Clair sites, to investigate whether the water or the sediment phase represented the primary source of contaminants and to examine the effect of enclosure of the mussels on contaminant uptake. No significant differences in body burdens were detected for any of the compounds between mussels placed in corrals containing uncontaminated sand and those with natural sediment, suggesting the water phase represents the xenobiotic source. Among three enclosure types of varying restriction there were no significant differences in the body burden of each compound indicating the effect of confinement on uptake is minimal. Weak negative correlations between body burden and body length existed for all compounds, although there were no significant differences between the sexes or, with the exception of PCB congener 118, among five indigenous species. PMID- 2331153 TI - The acute and chronic toxicity of ammonia to marine fish and a mysid. AB - The acute toxicity (96-hr LC50) of un-ionized ammonia to mysids (Mysidopsis bahia) and larval inland silversides (Menidia beryllina) was influenced by pH and salinity in a species specific manner. With mysids, NH3 was most toxic at pH 7.0 and less toxic at pH 8.0 and 9.0. In contrast, NH3 toxicity to inland silversides was greatest at pH 7.0 and 9.0 and lowest at pH 8.0. A drop in salinity from 31 g/kg to 11 g/kg uniformly increased toxicity to mysids over this pH range. In contrast, in silversides at 11 g/kg, NH3 toxicity was less at pH 7.0, greater at pH 8, and slightly less at pH 9, relative to the toxicity at 31 g/kg. Temperature had no significant effect on the acute toxicity of un-ionized ammonia with acclimated mysids tested at 18, 25 and 32.5 degrees C, but did have a small effect with acclimated larval sheepshead minnows (Cyprinodon variegatus) tested at 13, 25 and 32.5 degrees C. The chronic toxicity value (the geometric mean of the highest no-effect concentration and lowest effect concentration) at pH 8.0, 25 degrees C and 31 g/kg salinity is 0.061 mg NH3/L for inland silversides and 0.232 mg NH3/L for mysids; the acute:chronic ratio is 21.3 and 7.2, respectively. PMID- 2331154 TI - Field evaluation of predictions of environmental effects from a multispecies microcosm toxicity test. AB - The predictive validity of a multispecies-microcosm toxicity test was evaluated. Predictions of biological response to a complex effluent were made from dose response curves in laboratory tests and compared to observed effects in the receiving system. No effects on protozoan or macroinvertebrate communities were observed at the field site with effluent concentrations less than the chronic value of 1.7% effluent determined in laboratory tests. In addition, the microcosm test accurately predicted the magnitude of decreases in species richness in protozoan and macroinvetebrate communities in the receiving system at the first downstream site. Predictions of environmental effects for stations farther downstream were generally less accurate and too high, perhaps due to lack of persistence in the toxicity of the effluent. Stimulation of total biomass and algal growth were observed in both laboratory and field tests, but laboratory tests greatly overestimated the magnitude of enrichment responses in the receiving system. PMID- 2331155 TI - Evaluation of a 14-day static renewal toxicity test with Daphnia magna straus. AB - Two replicate 14-day static renewal chronic toxicity tests were conducted with Daphnia magna Straus for each of three test chemicals (boric acid, aniline, and 2,4-dichlorophenol). These tests were conducted at 24 +/- 2 degrees C. The objective of this study was the comparison of the 14-day test results with chronic values derived for the same chemicals from 21-day studies (20 degrees C). It was hypothesized that the comparison of the chronic data resulting from the two test regimes would support the shortening of the standard 21-day exposure period and reduce the cost of these labor intensive studies. The results of this study are as follows: 1. The 14-day test met the 21-day chronic test acceptability criteria in terms of control data associated with the mean number of broods/adult, mean total young/adult, mean brood size and survival. 2. A comparison of the results shows the similarity of the chronic values generated from the 14 and 21-day tests. In all cases, the chemical specific chronic values were within a factor of 2. The chronic values for 2,4-dichlorophenol generated from the two test regimens were virtually identical (i.e., 14-day--1.1 and 1.2 mg/L; 21-day--1.1 mg/L). 3. The comparison of the chronic values resulting from the 14 and 21-day tests supports the use of the 14-day exposure period. A shorter exposure period will help reduce the cost of these labor intensive studies without compromising their scientific integrity. PMID- 2331156 TI - Effect of environs and seasonality on metal residues in tissues of wild and pond raised crayfish in southern Louisiana. AB - Two commercially important species of Louisiana crayfish, Procambarus clarkii (Girard) and P. acutus acutus (Girard), from the Atchafalaya River Basin, from open ponds and from the sediment and water of these environs were sampled three times during two consecutive fishing (production) seasons. The abdominal muscle and hepatopancreatic tissue were analyzed separately. Lead, mercury, and cadmium, if present, were in concentrations below the detection limit. In the hepatopancreatic tissue, barium was present in concentrations below 8 mg/kg, copper 11-15 mg/kg, and iron below 640 mg/kg. Abdominal muscle samples had less than 3 mg/kg of most metals. Locations with the highest levels of metal residues in sediment were not necessarily locations where crayfish had the highest levels in their tissues. PMID- 2331157 TI - [Urology of the future: a network]. PMID- 2331158 TI - [The phenomenon of obstructive uropathy with minimal or no dilatation]. AB - Obstructive anuria does not necessarily show a marked dilatation of the urinary tract on evaluation with imaging techniques. A case with acute renal failure of this type is presented. We discuss why this condition is caused and how diagnosis can be made quickly. Likewise, we discuss the length of time we can defer renal diversion before rupture of the collecting system supervenes and, consequently, urinary extravasation. PMID- 2331159 TI - [Management of injury of the solitary kidney]. AB - Two cases of renal trauma are described herein. The diagnostic work up revealed the patients had solitary kidney. Trauma was classified as grade 1 and 2 and a conservative approach was adopted. The patient with grade 2 trauma was submitted to surgery one month following treatment. Preservation of the renal unit was achieved in both patients. Patient follow up at 16 years revealed no complications or sequelae from the injury. The diagnostic and therapeutic aspects of renal trauma in patients with solitary kidney are discussed. PMID- 2331160 TI - [Bladder endometriosis]. AB - Although uncommon, vesical endometriosis is considered an important disease entity due to the diagnostic difficulties it presents and the different therapeutic options that are available. A case of long-standing vesical endometriosis that caused considerable suffering to the patient is reported. The foregoing condition was refractory to hormone therapy and late radical surgical treatment by partial cystectomy and hysterectomy failed to achieve good results. The clinical and therapeutic aspects of the present case are compared with those reported elsewhere. We underscore the importance of biopsy by transurethral resection in its diagnosis as well as the need for a more effective therapeutic approach. PMID- 2331161 TI - [Renal carcinoma presenting as a multilocular cyst]. AB - Although it is not uncommon to find small foci of cystic degeneration in renal adenocarcinoma, it is uncommon to find these so extensive as to permit a preoperative diagnosis of multilocular cyst as in the present case. Several etiopathogenic mechanisms have been described. In the present case, the underlying mechanisms are likely to be tumor necrosis and intrinsic multilocular cystic growth. Arteriography is not the best diagnostic method and there are doubts as to the usefulness of punction aspiration. Prognosis remains unclear. PMID- 2331162 TI - [Retroperitoneal hemorrhage as a complication of renal angiomyolipoma]. AB - Renal angiomyolipoma (AML) is an uncommon, benign neoplasm of a hamartomatous origin that presents as multiple bilateral lesions occasionally associated with tuberous sclerosis, or as a single unilateral lesion. They are generally asymptomatic, and can manifest the following clinical triad: abdominal pain, palpable mass and hematuria. Retroperitoneal hemorrhage is a rare complication (9%). We report 3 cases of spontaneous rupture of renal AML with massive hemorrhage; two of these cases were associated with tuberous sclerosis. This complication was the presenting feature of renal AML in two cases. Radiologic diagnosis and management of this tumor type are highlighted. PMID- 2331163 TI - [Evaluation of extravesical ureteroneocystostomy in kidney transplantation]. AB - The present study evaluates extravesical ureteroneocystostomy, the technique used for reconstruction of the urinary tract in 120 kidney transplants. The urological complications ascribable to this technique were observed in 10% (12/120) and consisted of urinary extravasation (10), and ureteric obstruction (2). The treatment of the foregoing complications, which was successful in 8 cases, is described. The indications and advantages afforded by this technique in renal transplantation are discussed. PMID- 2331164 TI - [Microsurgical spermatico-epigastric diversion in the treatment of varicocele in pre-adolescent patients]. AB - Varicocele is not an uncommon condition in pre-adolescence. Internal spermatic vein phlebography provides insight into vascular anatomy and etiopathogenesis. Eighty-six cases treated by microsurgical spermatico-epigastric anastomosis (Belgrano technique) are reported. This technique has been shown to achieve a very high cure rate (98.8%). Several techniques of venous anastomosis are described and compared with the Belgrano technique. The results show that the latter is the ideal technique because it not only resolves reflux but also provides adequate venous drainage to the testis. PMID- 2331165 TI - [Changes in creatinine clearance and fractional sodium excretion by the remaining kidney after nephrectomy of the contralateral diseased kidney in the adult]. AB - Unilateral nephrectomy causes immediate changes in renal plasma flow, glomerular filtration, and fractional sodium excretion of the remnant kidney. The present study reviews some aspects of reports published elsewhere relative to renal function adaptation after unilateral nephrectomy and presents the observed changes in creatinine clearance, fractional sodium excretion at 6, 30 and 90 days following removal of kidneys with chronic urologic disease and poor function, in a total of 20 patients. The results obtained show a gradual increase of creatinine clearance in most of the patients, although this increase was not statistically significant. On the other hand, fractional sodium excretion rose significantly at 30 and 90 days after nephrectomy. These findings can be interpreted in the following way: among the regulatory mechanisms, at 6 days postnephrectomy there is a predominance of the effects of increased CINa load to the distal tubule with activation of the renin-angiotensin system, as well as those produced by sympathetic efferents characteristic of the immediate postoperative period. However, at 30 and 90 days, the effects that seem to predominate are due to the expansion of the volume of extracellular fluid. Data obtained at 90 days indicate that balance seems to become stable. PMID- 2331166 TI - [Endourologic treatment of tumors and pseudotumors of the upper excretory system]. AB - Thirteen patients with a benign tumor or pseudotumor of the upper urinary tract underwent endourological treatment on 17 occasions. These patients were divided into two groups according to the anatomopathological findings. Five patients comprised group I. Mean patient age, 57.3 years. These patients had a tumor in the excretory cavity. Endoscopic work up revealed 3 papillary necroses, 1 inflammatory polyp, 1 Von Brun islet. One ureterorenoscopy (biopsy + laser) and four percutaneous (tumor resection) procedures were performed. Eight patients comprised group II. Mean patient age, 59 years. Six patients had pyelocaliceal tumors and two patients had ureteric tumors. Histologic analyses revealed a noninvasive low grade tumor on six occasions and two fibroepithelial polyps. Two ureteric tumors and 1 pelvic tumor were treated by retrograde ureterorenoscopy (2 resections and 1 Nd/Yag laser photocoagulation). Five patients were treated percutaneously (resection alone or combined with Nd/Yag laser). Four patients received local chemotherapy. Patient follow-up ranged from 1 to 3 years. Tumor recurrence was observed in 3 patients treated by percutaneous resection. PMID- 2331167 TI - [Pelvic fibromatosis: a case with clinical urologic features]. AB - We report on a patient with chronic prostate disease diagnosed as having a pelvic desmoid tumor (abdominal fibromatosis localized to the pelvis) whose presenting features were those of complete acute urinary retention. The findings on initial examination led us to suspect a prostate neoplasm which, however, was discarded by the results of the radiographic work up. The clinical and pathologic findings are presented and attention is drawn to the possibility that these mesenchymal neoplasms can have urological presenting symptoms and signs. PMID- 2331168 TI - [The association of hypernephroma and dysfunction of the pyeloureteral junction. Apropos of a case]. AB - We report on a patient with a tumor coexisting with a congenital condition. The foregoing conditions are discussed separately and their clinical and radiological features are described and compared with the findings commonly reported elsewhere. Finally, the conclusions relative to this uncommon case and its atypical mode of presentation are put forward. PMID- 2331169 TI - [Eosinophilic cystitis]. AB - Another case of eosinophilic cystitis is reported. Special interest is placed in the incorrectly assigned nature of this disease entity. Most of the authors tend to subdivide eosinophilic cystitis into two subtypes with its own clinical, histological, and evolutive aspects: allergic eosinophilic cystitis (AEC) and eosinophilic cystitis (EC). Several hypotheses have been put forward to explain its origin which, however, remains unclear. There is no specific treatment and its course tends to develop towards chronicity, with periods of remission and unpredictable exacerbation that warrant continuous monitoring. Diagnosis is by anatomopathological findings and differential diagnosis is warranted to distinguish it from bladder neoplasm (with which it is invariable confused), tuberculosis, etc. PMID- 2331170 TI - [Metastatic renal carcinoma of the breast. Presentation of 2 cases diagnosed by fine-needle aspiration puncture]. AB - Two cases of breast metastases from renal carcinoma are described herein. One patient underwent nephrectomy two years earlier and the other patient presented with bilateral involvement. The cytological features gleaned from fine needle aspiration biopsy are described. The diagnostic value of fine needle aspiration is underscored. This procedure makes surgery unnecessary and, furthermore, permits instituting a more adequate therapy. PMID- 2331171 TI - [Elongation of the balano-preputial frenulum using a very simple technic]. AB - A new technique to achieve, elongation of frenulum is described. The procedure is simple, exsanguine, and can be performed quickly. The results obtained with this procedure is similar to those obtained with traditional techniques. PMID- 2331172 TI - Experience with our first 400 treatments with ESWL and URS. AB - From September 1988 to April 1989, 400 patients with stones in the calix (40%), in the renal pelvis (45%), in the ureter (15%) and with staghorn calculi (5%), underwent shock wave treatment. In the majority of patients therapy was carried out with general anesthesia. Disintegration was achieved in 95% of stones in the kidney and 44% of stones localized in the ureter following in situ ESWL. The ureteronephroscopy and stone push-up with replacement into the renal pelvis was performed in 56% of ureteral calculi. The average number of impulses to achieve disintegration was 1,850. In 20 patients 4,000 shock waves were necessary. We studied these patients with echotomography, CT scan and magnetic resonance imaging 48 hours after the treatment. The aim of this trial was to assess the efficacy and cost benefit ratio of the Tripter X1 lithotripter. PMID- 2331173 TI - The dog as natural reservoir host for Paragonimus uterobilateralis in Liberia, West Africa. PMID- 2331174 TI - The use of isoenzyme electrophoresis in the taxonomy of Strongyloides. AB - The limited usefulness of traditional taxonomic methods combined with the discovery of a Strongyloides parasitic in man in Papua New Guinea (PNG) that resembles S. fuelleborni, a parasite of man and other primates in tropical Africa, has precipitated the need to apply new methods to the taxonomy of the genus. In this study isoenzyme electrophoresis has been used on Strongyloides isolates of many different origins. Cluster analysis of the data suggested that existence of three main groups within the material considered, consisting of (1) isolates of S. stercoralis, (2) isolates from PNG domestic animals, and (3) isolates from PNG man and African non-human primates. The taxonomic implications of these groups are considered. PMID- 2331175 TI - Response of female sandflies (Lutzomyia longipalpis) to pheromone-baited sticky traps in the laboratory. AB - Response of virgin female Lutzomyia longipalpis Lutz & Nevia (Diptera: Psychodidae), contained in a 60-cm3 net cage, to sticky traps was significantly greater when the traps were baited with extract of male pheromone glands. Results confirm that the response of females to male pheromone does not necessarily depend upon the presence of a host. PMID- 2331176 TI - Histology and ultrastructure of pheromone secreting glands in males of the phlebotomine sandfly Lutzomyia longipalpis. AB - Well-defined pheromone-producing glands are present on the third and fourth abdominal segments of male Lutzomyia longipalpis. Each gland consists of numerous large secretory cells. The individual cells have a complicated 'end-apparatus' and central reservoir which are connected directly to the exterior via a small chitinized duct. This is the first ultrastructural study of pheromone secreting cells of Diptera. PMID- 2331177 TI - Incidence and diel pattern of oviposition outdoors of the mosquito, Aedes aegypti (L.) (Diptera: Culicidae) in Trinidad, W.I. in relation to solar aspect. AB - The incidence and diel patterns of oviposition of domestic Aedes aegypti in Trinidad, West Indies during the middle of the wet season (July and August) was compared, using modified ovitraps, in unshaded peridomestic outdoor sites facing east or west. Sites close to each other along a transect differed greatly in the total eggs they received, 18.2% of sites receiving 50.6% of the eggs. Sites receiving most eggs were close to other breeding sites. The incidence of oviposition in sites facing west, as measured by the number of eggs laid (greater than 59%) and by the number of occurrences of eggs (greater than 57%), was greater than in sites facing east. The diel pattern of oviposition was closely similar in sites facing east and west, indicating that the sun's azimuth at the moment of oviposition does not determine whether a female lays in sites facing east or west. The diel pattern of oviposition resembled an earlier study in being bimodal but differed from it in featuring a much larger morning peak (comprising more than 34% of eggs laid v. about 5% in the earlier study). This bimodal pattern closely resembles the diel periodicity of landing on humans described previously by several authors and is probably close to the typical oviposition pattern for Ae. aegypti; an artefact may have modified the oviposition periodicity characterized earlier. In the evening significantly more eggs were laid in sites facing west than in sites facing east. These findings have implications for effective placement of ovitraps for surveillance or suppression of Ae. aegypti, and give rise to an hypothesis which invokes responses to microclimate to account for the form of the bimodal oviposition pattern. PMID- 2331178 TI - Diel patterns of oviposition indoors of the mosquito, Aedes aegypti (L.) (Diptera: Culicidae) in Trinidad, W.I.: a preliminary study. AB - Diel patterns of oviposition of domestic Aedes aegypti were monitored early in the dry season in two situations indoors in Trinidad, West Indies. In kitchens, a large, well defined peak of oviposition (comprising more than 56% of eggs laid) occurred two to four hours before sunset and a smaller peak (about 16% of eggs laid) occurred within the two hours after sunrise. In living rooms, the afternoon peak was better defined and larger (more than 86% of eggs laid) and occurred later, within the two hours before sunset; the morning peak coincided with its counterpart in kitchens but was much smaller (less than 2% of eggs laid); some oviposition (about 8%) occurred at night but only during the two hours after sunset. Peaks of oviposition corresponded with times of greater human presence or activity in the two kinds of room. Similarities and differences between these patterns and those of oviposition outdoors and of landing indoors are discussed in the context of possible determinants of oviposition behaviour. PMID- 2331179 TI - The pig as an experimental host of Taenia saginata (Ethiopia and Madagascar strains). PMID- 2331180 TI - Predation of Pomacea canaliculata (Ampullariidae) on adult Biomphalaria peregrina (Planorbidae). PMID- 2331181 TI - A comparative study of fecal occult blood tests for early detection of gastrointestinal pathology. AB - The question of what the most accurate and efficient fecal occult blood testing method is for the early detection of pathological gastrointestinal tract bleeding continues to be intensely debated. In this prospective study, the following five uniquely different slide tests were investigated in 120 patients who underwent gastrointestinal tract investigation: (1) a combination monoclonal antibody guaiac test (Monohaem); (2) an immunologic assay, enzyme-linked immunosorbent assay, with (3) a highly sensitive guaiac test (Fecatwin S/Feca enzyme immunoassay), (4) a popular guaiac test (Coloscreen III) (comparable with Hemoccult II), and (5) Coloscreen III/VPI (ie, with vegetable peroxidase) inhibitor. Computerized data show efficiency values for detection of fecal occult blood by Coloscreen III-Fecatwin S-Monohaem combined, 93%; Coloscreen III Monohaem combined, 91%; Monohaem, 87%; Coloscreen III/VPI, 82%; Coloscreen III, 79 percent; enzyme-linked immunosorbent assay, 77%; and Fecatwin S, 68%. Results of sensitivity, specificity, false-positive and false-negative test results, tests' predictive value, simplicity, and costs of tests in this clinically based study suggests that the concomitant use of the monoclonal, monospecific test for human hemoglobin and an appropriately sensitive guaiac test is a potentially valuable approach to mass screening and early detection of occult bleeding gastrointestinal tract pathology, including colorectal cancer. PMID- 2331182 TI - Effects of reduction in dose and discontinuation of hydrochlorothiazide in patients with controlled essential hypertension. AB - We studied the effects of a reduction in dose of hydrochlorothiazide from 50 to 25 mg/d, and its discontinuation for up to 22 months in 36 well-controlled hypertensive patients. Hydrochlorothiazide was discontinued if the diastolic blood pressure remained less than or equal to 94 mm Hg after a 6-month period on the lower dose of hydrochlorothiazide. No other changes were made in medications or diet. Sitting systolic blood pressure rose from 135 +/- 15 mm Hg to 140 +/- 14 mm Hg on reduction of the hydrochlorothiazide dose and rose still further to 145 +/- 20 mm Hg on discontinuation. Even greater increases in standing blood pressure were observed. There were no significant effects on the diastolic blood pressure with reduction of dose or discontinuation of hydrochlorothiazide. A significant decrease in the serum uric acid and a rise in serum potassium occurred. There were no changes in serum glucose or lipids on reduction in the dose of hydrochlorothiazide; whereas, with discontinuation, the serum lipids and hemoglobin A1C fell significantly. These results suggest that the benefits of a reduced dose of hydrochlorothiazide may not be as great as considered heretofore. PMID- 2331183 TI - Presence and prognostic significance of antilymphocyte antibodies in symptomatic and asymptomatic human immunodeficiency virus infection. AB - The presence of antilymphocyte antibody (ALA) in patients with the acquired immunodeficiency syndrome (AIDS), identified in a previous study, was confirmed by testing a population of 200 patients with AIDS. Of these, 88% had significant levels of ALA vs only 8% of a control group of patients with non-AIDS-related diseases. In a prospective study, the levels of ALA were determined in 61 patients with AIDS-related complex who were followed up for 18 to 30 months. During this interval, 31 (67%) of 46 patients with significant elevation of ALA levels developed AIDS, while none of 15 patients without elevation of ALA levels progressed to AIDS. In a group of 85 apparently healthy homosexual men, also followed up for 18 to 30 months, a significant number of those with high levels of ALA developed clinically apparent disease, while those with low levels did not. These results show that the amount of ALA correlates with the present clinical status as well as the future risk of developing immune deficiency. PMID- 2331184 TI - Sexuality in older women. AB - A host of biological and psychosocial factors play an important role in age related changes of female sexuality. The most important of these are the availability of a sexually active partner and presence of concurrent illnesses. Some of the age-related changes in physiological indicators of sexual function, such as vaginal blood flow, are the result of estrogen deficiency, and as such are essentially reversible. Despite the inherent limitations of many studies in female sexuality, a significant degree of objective measurements has been reported in the literature. Future research should focus on developing appropriate techniques for quantitative estimation of sexual response in women. The need for love and sexual intimacy does not diminish with age, and sexual history should be part of the clinical evaluation of older patients. PMID- 2331185 TI - Colorectal cancer detection in the practice setting. Impact of fecal blood testing. AB - To assess the contribution of fecal blood testing to cancer detection in a clinical practice setting, we studied records from 160 patients with both a new tissue diagnosis of colorectal adenocarcinoma and a preceding stool blood test (HemoQuant, Mayo Medical Laboratories, Rochester, Minn) determination. In this group, 71% had suggestive colorectal symptoms (particularly stool changes, overt bleeding, and abdominal pain) or anemia at presentation, and 29% were asymptomatic. Fecal blood levels remained normal in more than 40% of both symptomatic and asymptomatic patients. In only 26 patients (16% overall) was an abnormal fecal blood level the sole heralding feature, but this subset of patients had a more favorable stage. Fecal blood levels were higher with advanced, larger, and more proximal tumors and with stools collected before purgation. We conclude that, in the practice setting, fecal blood level elevation alone is an uncommon but important manner of colorectal cancer presentation, most cancers present with symptoms, and fecal blood levels are often normal in both symptomatic and asymptomatic patients. PMID- 2331186 TI - The do-not-resuscitate order. Still too little too late. AB - We reviewed the records of 274 consecutive deaths at the Milton S. Hershey Medical Center, Hershey, Pa, occurring through May 1988 to examine the approach of physicians, patients, and families in making the decision to invoke the "do not-resuscitate" order. Of these 274 patients who died, 171 (62%) had do-not resuscitate orders. Of these 171 patients, 86 (50%) were judged fully mentally competent on admission to the hospital; 44 (51%) of these 86 fully competent patients were included in the decision to withhold resuscitative efforts. In the remainder, the family was usually involved in the decision without input from the patient. Only 6 patients (4%) were admitted to the hospital with a preexisting do not-resuscitate order. For the remainder, the do-not-resuscitate order was written a mean of 8.5 days following admission and 3.3 days before death. Documentation of this order with a specific progress note was universal. The principle reason cited for a do-not-resuscitate order was the presence of irreversible terminal disease in 52% and an unacceptable quality of life in 33%. When considered separately, patients with a principle diagnosis of malignant neoplasm had a do-not-resuscitate order written 80% of the time. Of 88 such patients, 48 (55%) were fully competent at admission. In turn, 36 (75%) of these patients participated in the do-not-resuscitate decision. Nursing activities were quantified for the 24 hours preceding and the 24 hours following the do-not resuscitate order. No difference could be found comparing these two periods whether the comparison was made on the general hospital ward or in the intensive care unit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331187 TI - Body weight as a risk factor in the elderly. AB - To determine whether body weight is a risk factor for mortality among older persons, we analyzed body mass index (weight [kilogram]/height [square meter]) data for 4710 white, National Health and Nutrition Examination Survey respondents who were aged 55 to 74 years during 1971 through 1975, in relation to their survival over an average of 8.7 years of follow-up. In a multivariate analysis that controlled for elevated blood pressure, smoking, and poverty, we found no additional risk associated with weight among women and a statistically significant, but moderate, additional risk (relative risk, 1.1 to 1.2) among men in the upper decile (body mass index, greater than or equal to 30 kg/m2). In contrast, low weight (body mass index, less than 22 kg/m2) was associated with increased mortality (relative risk, 1.3 to 1.6) except for women aged 55 to 64 years. We conclude that the accepted definition of overweight (body mass index, greater than or equal to 27.8 kg/m2 [men] or greater than or equal to 27.3 kg/m2 [women]) lacks specificity and may be inappropriate for older persons who do not have weight-related medical conditions. The low-weight mortality association, consistently demonstrated, deserves serious scrutiny. PMID- 2331188 TI - The duration of Holter monitoring in patients with syncope. Is 24 hours enough? AB - To determine the incremental yield of ambulatory monitoring in the evaluation of syncope, three serial 24-hour Holter recordings were obtained in a consecutive series of 95 patients with syncope, the cause of which was not explained by history, physical examination, or 12-lead electrocardiogram. The mean age of patients was 61 years and 41% were men. Major electrocardiographic abnormalities were found in 26 patients (27%), including unsustained ventricular tachycardia (19 patients), pauses of at least 2 seconds (8 patients), profound bradycardia (1 patient), and complete heart block (1 patient). The first 24-hour Holter recording had at least one major abnormality in 14 patients (15%) (95% confidence interval, 8.3% to 23.4%). Of the 81 patients without a major abnormality on the first Holter recording, the second Holter recording had major abnormalities in 9 (11%) (95% confidence interval, 5.1% to 20.0%). Of the 72 patients without a major abnormality on the first two Holter recordings, only 3 patients (4.2%) had a major abnormality on the third Holter recording (95% confidence interval, 0.8% to 11.7%). Four factors were significantly associated with an increased likelihood of a major abnormality on 72 hours of monitoring: age above 65 years (relative risk, 2.2), male gender (relative risk, 2.0), history of heart disease (relative risk, 2.2), and an initial nonsinus rhythm (relative risk, 3.5). These results suggest that 24 hours of Holter monitoring is not enough to identify all potentially important arrhythmias in patients with syncope. Monitoring may need to be extended to 48 hours if the first 24-hour Holter recording is normal. PMID- 2331189 TI - Do the elderly sue physicians? AB - We reviewed malpractice data from the state of Wisconsin for 1983 and 1984 to determine the frequency and the outcome of malpractice litigation by the elderly. Research data were obtained from court dockets filed with Wisconsin's Patients Compensation Panel and from 281 attorneys who provided the age for 431 claimants. The results showed that 10.0% of malpractice suits in Wisconsin were filed by the elderly during the study years. When we compared the frequency of litigation with the use of the health care system (number of hospitalizations and inpatient days), the elderly were significantly less likely than younger persons to initiate malpractice litigation despite greater exposure to potential negligence. However, once a malpractice suit was filed, there was no significant difference between older and younger litigants in the disposition of the case or in the likelihood of being the prevailing party when a finding or award was made. These findings suggest that the elderly are less likely to file malpractice claims against health care providers than would be expected given their use of the health care system. This finding may be related to social, economic, and legal barriers to malpractice litigation by older adults. PMID- 2331190 TI - Quinine hepatotoxicity. An underrecognized or rare phenomenon? AB - Quinine-induced hepatic injury has been reported very rarely. We report a case involving a patient with an apparent hypersensitivity to quinine, manifested by a clinical syndrome mimicking a viral illness and a mixed hepatocellular cholestatic liver injury pattern. We briefly review the unusual literature on this topic, which features many cases of hypersensitivity to the optical isomer of quinine, quinidine; yet, to our knowledge, there has only been one prior report of quinine hepatotoxicity. PMID- 2331191 TI - Anesthetic choice for the asthmatic patient. PMID- 2331192 TI - Chronic fatigue: psyche or sleep? PMID- 2331193 TI - Some pitfalls in disease screening. PMID- 2331194 TI - Do not resuscitate orders. PMID- 2331196 TI - Baby dolls in dementia. PMID- 2331195 TI - Leptospirosis as a cause of uveitis. PMID- 2331197 TI - Prevalence of Campylobacter pylori in a tertiary care hospital in the mid Atlantic United States. PMID- 2331198 TI - Megaloblastic pancytopenia associated with dapsone and trimethoprim treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. PMID- 2331199 TI - Limitations of fecal occult blood testing. PMID- 2331200 TI - Depression. Underrecognition and undertreatment by psychiatrists and other health care professionals. PMID- 2331201 TI - Graves' ophthalmopathy. Is it really thyroid disease? PMID- 2331202 TI - Material safety data sheets. Caveat emptor. AB - Numerous hazardous chemicals are present in workplaces and the environment. Physicians are likely to be increasingly challenged with the evaluation of individuals exposed to these chemicals. Recent legislation mandates the creation of material safety data sheets that describe the composition and toxicity of hazardous compounds. This legislation has also greatly increased the availability of material safety data sheets to workers and physicians. While these can be of great assistance in the evaluation of exposed individuals, they often contain deficiencies that preclude the prudent physician from relying exclusively on them. A few typical material safety data sheets are reviewed to illustrate what one can expect to find. PMID- 2331203 TI - A public health model for cardiovascular risk reduction. Impact of cholesterol screening with brief nonphysician counseling. AB - To examine the impact of cholesterol screening with brief nonphysician counseling on cardiovascular risk factors, 886 employees at a large financial services firm underwent fingerstick screening followed by brief (3- to 5-minute) counseling by a registered nurse. At the 6-month follow-up, there were significant declines in total cholesterol levels (5.9 to 5.5 mmol/L [228 to 213 mg/dL]), weight (78 to 75 kg), blood pressure (119/78 to 115/75 mm Hg), and number of people reporting smoking (16.8% to 14.5%) among participants with a baseline cholesterol value of 5.2 mmol/L (200 mg/dL) or greater. A randomized experiment was conducted on 137 participants initially classified as having a "borderline-high blood cholesterol" level (5.2 to 6.2 mmol/L [200 to 239 mg/dL]) to test the impact of frequency of follow-up. Those receiving frequent follow-up (cholesterol measurement and brief counseling at 2, 4, and 6 months) reported significantly greater dietary change and demonstrated a trend toward greater declines in total cholesterol compared with those receiving follow-up at 6 months only. The results of this study support the feasibility and efficacy of cholesterol screening utilizing brief nonphysician counseling on multiple cardiovascular risk factors and suggest an enhanced effect when patients receive more frequent follow-up. PMID- 2331204 TI - Improvement in physicians' counseling of patients with mental health problems. AB - This study evaluated the impact of two interventions: (1) detailed feedback about a patient's mental health problem and desires for specific mental health interventions, and (2) a counseling protocol on medical residents' management of patients with mental health problems. These patients were seen in either a control, feedback, or feedback/protocol clinic. Immediately following their medical visit we found the following differences between feedback and control patients: feedback patients reported that the stress counseling they received was more valuable, and they were more satisfied with their physician; feedback patients also perceived greater decreases in the amount of overall stress experienced, and reported greater increases in their perceived control over stress. There were no outcome differences between feedback and feedback/protocol patients. We conclude that the feedback provided in this study can enhance physicians' ability to counsel primary care patients with mental health problems. PMID- 2331205 TI - The influence of cortical lesions on penicillin induced convulsive activity in the awake rat. AB - 1. Experiments were performed to investigate the effects of cortical lesions on convulsive behaviour. Rats were lesioned in the left motor or sensory cortex by aspirating cortical tissue 2 to 3 months prior to the elicitation of convulsions. Convulsions were induced in the awake rats by the GABA antagonist Na-penicillin (Na-PCN) which was applied into the superficial layer of the foreleg field of their right motor cortex. Convulsive activity was recorded by means of the EEG. 2. The time courses of convulsive cortical activity were similar in the animals without or with a cortical lesion. Generalized seizures belonged to the tonic clonic type in both intact and lesioned rats. 3. The early period of convulsive activity was described by the time to the onset (latency) of the first convulsive potential, jerk and seizure, and by the mean repetition rate of jerks during the first ten minutes, and the duration of the first generalized seizure. None of these parameters was significantly affected by a cortical lesion. 4. The median duration of the convulsive activity in intact animals was 162 min. In rats with a lesion in the sensory cortex it raised to more than 540 min while a lesion of the motor cortex increased the median duration to more than 273 min. The differences between intact and lesioned rats were significant (p less than 0.01 and p = 0.05, respectively). 5. The median time to the onset of the last generalized seizure in intact rats corresponded to 92 min with respect to the time of Na-PCN application. In rats with a lesion of the sensory cortex the last seizure was generated 433 min and in animals with a lesion of the motor cortex 167 min after Na-PCN treatment of the motor cortex of one side. This increase of latency of the last seizure was significant for the rats with a lesioned sensory area (p less than 0.02) or motor area (p = 0.05) compared to that of the intact rats. Additionally, the number of generalized seizures was significantly (p less than 0.01) increased by both groups of rats with a lesion of the motor or sensory cortex. 6. It is suggested that a substantial lesion of the cortex decreases predominantly the intrinsic cortical inhibition thus destabilizing brain function. This destabilizing effect becomes pronounced under the condition of superimposed suppression of the GABAergic cortical component. It is concluded that the intrinsic cortical inhibitory mechanism which in the intact brain acts against hyperexcitation and prevents the development of neuronal synchronization, i.e. the formation of seizures, becomes less effective in performing this task once an abnormal brain activation has developed. PMID- 2331206 TI - Separate populations of neurons in the oculomotor nucleus project to the cerebellum and the abducent nucleus. A retrograde fluorescent double-labelling study in the cat. AB - Retrograde transport of fluorescent substances was used in order to investigate possible branching of axons from neurons in the oculomotor nucleus in the cat. Rhodamine-B-isothiocyanate (RITC) was injected into the cerebellar hemisphere, while Fluoro-Gold was implanted into the abducent nucleus. Neurons single labelled with either of the dyes were found in the oculomotor nucleus in all cases, but no double-labelled neurons were found. The labelled cells were smaller than motoneurons and located in partly overlapping areas along the dorsal border of the oculomotor nucleus, with the RITC labelled cerebellar projecting cells concentrated medially and the Fluoro-Gold labelled neurons projecting to the abducent nucleus concentrated laterally. The RITC labelled cells were found throughout the rostrocaudal extent of the nucleus, while the Fluoro-Gold labelled cells were mainly found caudally. The present findings demonstrate that oculomotor neurons projecting to the feline cerebellum and abducent nucleus represent separate cell populations. PMID- 2331207 TI - EEG-spectra parameters distinguish pathophysiological and pharmacological influences on the EEG in treated schizophrenics. AB - Movement related EEG segments of one second duration were analyzed by Fast Fourier Transformation in the Bereitschaftspotential paradigm in 31 neuroleptic treated schizophrenics compared to 21 matched controls. Schizophrenics demonstrated a higher theta mean power density and center frequency together with a lower radius of gyration, skewness and kurtosis in the theta band than controls. The higher theta power in the faster frequency range of the theta band is probably due to neuroleptic medication, but the higher theta power in the lower frequency range may be related to the disease. In the alpha band the schizophrenic group differed from controls by a lower center frequency, higher radius of gyration and skewness. Both groups did not differ in the alpha mean power density. The lower center frequency reflects the fact that alpha activity is distributed towards the lower frequency range which seems to be a consequence of the neuroleptic treatment. The more widespread alpha activity (higher radius of gyration) in schizophrenics indicates less frequency stability, i.e., more desynchronized alpha rhythm which corresponds to a highly activated functional state. By means of the applied spectral parameters more detailed quantitative descriptions of the power distributions in each frequency band are available, allowing to test hypothesis in relation to underlying physiological processes. PMID- 2331208 TI - Muscarinic receptor binding in forebrain and cerebellum during sleep-waking states in the rat. PMID- 2331209 TI - Extreme temperament and diagnosis. A study in a psychiatric sample of consecutive children. AB - We report on an epidemiological-clinical study of the New York (NY) Longitudinal Study temperament model in a consecutive sample of children (N = 814) referred to a child psychiatric center. Temperament comparisons in this clinical population were made by using temperament normative values obtained in previous random samples of the general population in the greater Quebec City (Canada) area. Different clinical diagnostic groups (externalized disorders, developmental delays, and mixed disorders) were derived from a review of the entire hospital charts in which the interrater reliability was tested and performed "blind" to temperament scores. The diagnostic groups were confirmed through discriminant function analyses. The results (1) replicated, in this child psychiatric population, two factors of temperament similar to those previously found in random samples of our general population; (2) showed, in the psychiatric population of children, an overproportion of difficult temperaments on both factors; (3) confirmed conversely that a large proportion of children referred for a disorder did not present with an extreme temperament, and, therefore, an extreme temperament and a clinical disorder were not equivalent; and (4) suggested a specificity in the relationship between particular temperament factors and the type of clinical problem. Temperament factor 1 (withdrawal from new stimuli, low adaptability, high intensity, and negative mood) was found to be more associated with externalized disorders (opposition, conduct, or attention deficit disorders), whereas temperament factor 2 (low persistence, high sensory threshold, and high mobility) was found to be more associated with specific developmental delays. The findings provided leads for future clinical research on temperament, family functioning, and child psychiatric diagnoses. PMID- 2331211 TI - A National Health Service. PMID- 2331210 TI - Uncommon troubles in young people: prevalence estimates of selected psychiatric disorders in a nonreferred adolescent population. AB - A two-stage epidemiologic strategy was used to estimate the lifetime prevalence of selected DSM-III-defined psychiatric disorders in a county-wide secondary school population (N = 5596). Screening tests used in the first stage included items based on DSM-III criteria for eating disorders and panic disorder, as well as the Leyton Obsessional Inventory-Child Version and the Beck Depression Inventory. Based on interviews (n = 356) by clinicians in the second stage, the lifetime prevalence of anorexia nervosa was 0.2%; bulimia, 2.5%; panic disorder, 0.6%; obsessive-compulsive disorder, 1.9%; major depression, 4.0%; dysthymic disorder, 4.9%; and generalized anxiety disorder, 3.7%. While rates of mental health service utilization varied greatly by diagnosis, only 41% of students who were assigned both a diagnosis and a rating of impairment had received any kind of clinical attention. PMID- 2331212 TI - Liver transplantation for polycystic liver disease. AB - Four female patients with severe complications of polycystic liver disease were treated with liver replacement; two patients were also given kidneys from their liver donors. All four of the patients were suffering from extreme fatigue. Three of the recipients have survived for 8, 11, and 60 months with normal liver function and present good health. The fourth patient recovered from a liver kidney transplantation, but 5 months later, fulminant hepatic failure developed in this patient due to hepatitis B virus, and she died despite emergency hepatic retransplantation. PMID- 2331213 TI - Combined therapy for inflammatory breast cancer. AB - The prognosis for patients with inflammatory breast cancer has improved in recent years. This review was undertaken to evaluate current management in three Milwaukee (Wis) hospitals and to identify determinants of prognosis. We identified 25 patients with inflammatory breast carcinoma diagnosed between 1967 and 1987. Most of the patients were treated with combination chemotherapy and radiation therapy, and 10 had mastectomies. The 5-year survival of patients without initial distant metastases was 24%. The 5-year survival of patients who received chemotherapy before local treatment was 40%. Patients who had clinically involved axillary nodes or a palpable mass in the breast had poorer survival than those who did not; the presence of dermal lymphatic invasion had no significant effect on survival. Initial chemotherapy has become an important part of the care of patients with inflammatory breast cancer. It remains uncertain whether mastectomy improves on irradiation in achieving local control or improves survival. PMID- 2331215 TI - The right colon as a target organ of nonocclusive mesenteric ischemia. Case report and review of the literature. AB - Nonocclusive mesenteric ischemia is a poorly understood process that infrequently complicates states of hemodynamic compromise. The right side of the colon appears to be particularly sensitive to this pathologic event. In a 25-year-old man, spinal shock from a gunshot injury to the thoracic spinal cord resulted in right colon necrosis from nonocclusive mesenteric ischemia. The anatomic and physiologic characteristics of the mesenteric circulation to the right colon that lead to this risk for nonocclusive mesenteric ischemia were studied. PMID- 2331214 TI - Adaptive changes in ileal mucosal nutrient transport following colectomy and endorectal ileal pull-through with ileal reservoir. AB - To study ileal mucosal function when used in an ileal reservoir or ileostomy, eight dogs underwent colectomy and endorectal ileal pull-through with creation of a lateral ileal reservoir. Ileal mucosal biopsy specimens were obtained at the initial operation, from the ileostomy and dormant ileal reservoir at the time of ileostomy closure, and from the reservoir 3 months later. Rates of uptake for four different substrates were determined by radioactive absorption techniques. Absorption of carbohydrates, amino acids, and bile acids was markedly decreased and of short-chain fatty acid mildly reduced in ileal reservoir mucosa compared with normal ileum, largely owing to a decrease in reservoir absorptive surface area from flattened villi. Reservoir uptake of the substrates evaluated within 3 months after operation was similar to that for normal colonic mucosa. Uptake of all measured substrates from ileostomy mucosa approximated that of normal ileum. The use of short ileal reservoirs and the avoidance of stasis may favor reduced bacterial growth and increased nutrient absorption. PMID- 2331216 TI - Phagocyte function after splenic autotransplantation. AB - This study was designed to examine the role of splenectomy and autotransplantation with regard to the leukocyte/differential cell counts and the function of peripheral blood phagocytes. Eleven groups of 40 Wistar male rats in each group either underwent total splenectomies or sham operations. The splenectomized groups underwent autotransplantations with 10% through 90% of the weight of the intact spleen. The leukocyte count and the oxidative burst response of the blood leukocytes were measured in each group. It was shown that a total splenectomy did not alter the leukocyte/differential cell counts. Furthermore, the blood picture remained basically unchanged after an autotransplantation with 10% through 90% of the weight of the intact spleen. The phagocyte oxidative burst response was measured by chemiluminescence. The chemiluminescence response of these cells was reduced after a total splenectomy. The phagocyte oxidative burst response returned to normal levels following an autotransplantation. There was no correlation between the amount of autotransplanted spleen and the degree of the oxidative burst response. These findings indicated that a splenectomy results in a diminished phagocyte oxidative burst response and that a spleen autotransplantation returns this function to normal levels. PMID- 2331217 TI - Mesenchymal hamartoma of the liver. A 35-year review. AB - Mesenchymal hamartoma of the liver occurs almost exclusively in infancy and childhood, with approximately 140 total cases reported. We report the experience with 18 patients at the Childrens Hospital of Los Angeles (Calif) during the past 35 years. The charts of all patients with mesenchymal hamartoma were retrospectively reviewed. The mean age at presentation was 16 months. Thirteen patients were symptomatic, presenting with increasing abdominal distention. Physical examination revealed an abdominal mass or hepatomegaly. Ultrasonography and computed tomography were the most useful diagnostic tests. Fourteen patients underwent resection; 9 underwent hepatic resection and 5 underwent excision of the tumor only. One patient had marsupialization, 1 underwent a biopsy only, and 2 died of unrelated causes and the hamartoma was found incidentally at autopsy. In all instances, a large cystic mass with well-demarcated margins was found. Three patients were unavailable for follow-up and 13 patients were alive and well 1 month to 24 years (mean, 5 years) after diagnosis. Recurrence or malignant transformation was not noted. A presumptive diagnosis can be made preoperatively by normal laboratory values and a combination of ultrasonography and computed tomography. We recommend excision of the tumor in all patients once the diagnosis is made, with the expectation of complete recovery. PMID- 2331218 TI - Medullary carcinoma of the breast. Overdiagnosis of a prognostically favorable neoplasm. AB - We reviewed 30 cases of breast cancer originally diagnosed as medullary carcinoma during a 10-year period. Of the 30, only 9 proved to be "typical medullary carcinoma" with the associated favorable prognosis. Seven of the remaining 21 cancers were reclassified as "atypical medullary carcinoma," and the remaining 14 were nonmedullary cancers. Overdiagnosis of medullary carcinoma could lead to inappropriately conservative therapy, since medullary carcinoma is a prognostically favorable neoplasm. Those involved with diagnosis and treatment of patients with breast cancer should be aware of this potential problem. PMID- 2331219 TI - The effects of hyperbaric oxygen on free flaps in rats. AB - The effects of hyperbaric oxygen on survival were investigated in free flaps and island flaps. Skin flaps transplanted following 18, 21, and 24 hours of preservation at 24 degrees C demonstrated survival rates of 20%, 10%, and 0%, respectively. Treatment with hyperbaric 100% oxygen improved the survival rates to 66%, 67%, and 40%. A preservation time of 21 to 24 hours at room temperature appears to be the threshold of irreversible ischemic damage. In acute island flaps, flap survival was improved significantly from 35% to 53% and 64% of the random flap area by preoperative or postoperative treatment, respectively. Prolonged preoperative and postoperative treatment improved survival to 66%. PMID- 2331220 TI - Nonobstructing colonic dilatation and colon perforations following renal transplantation. AB - Nonobstructing colonic dilatation has not been commonly reported following renal transplantation, and colon perforations carry a high morbidity and mortality in this population. During a 7-year period, nonobstructing colonic dilatation developed in 13 adults 1 to 13 days after renal transplantation. Twelve (92%) of the 13 had poorly functioning allografts. Five (83%) of the 6 with and 2 (29%) of the 7 without colonoscopy had resolution of nonobstructing colonic dilatation. Of the seven right-sided colon perforations during this period, six were associated with nonobstructing colonic dilatation. An additional 4 patients had diverticular perforations in the left colon. Of a total of 11 patients with colon perforation, 7 had surgery within 24 hours of the perforation and 6 (86%) of these survived. Only 1 (25%) of the 4 having surgery more than 24 hours later survived. Six of the survivors retained functioning allografts. Nonobstructing colonic dilatation seems to be a potential complication of poor graft function after renal transplantation, and colonoscopy is effective in its treatment. In patients with colon perforations, early surgery and reduced immunosuppression are essential in decreasing mortality. PMID- 2331221 TI - Exertional disruption of axillofemoral graft anastomosis. 'The axillary pullout syndrome'. AB - Five cases of exertional disruption of the axillary anastomosis occurred at intervals of 13 to 30 days after axillofemoral polytef (polytetrafluoroethylene [PTFE]) graft insertion. Graft evulsion was preceded by effort and heralded by axillary pain, an expanding hematoma, and a pseudoaneurysm formation. Proximal control of the subclavian artery by a supraclavicular approach or balloon allowed safe wound exploration. Successful reconstruction required lengthening of the graft or replacement. Secondary disruption occurred with simple repair. Although temporary postoperative brachial plexus neuropathy was common, no significant hand ischemia was noted. Twenty-two reports of axillary anastomotic disruption were made to the Food and Drug Administration, Washington, DC, during a 2-year period, and one manufacturer of polytef grafts provided data on 10 reports received throughout 7 years. Surface anatomy measurements in 20 control patients demonstrated that arm abduction and lateral flexion of the body increased the distance between the axillary and femoral arteries by a mean of 15.5%. Similar measurements taken from the proximal axillary artery showed a mean length increase of less than 10%. This complication may be avoided by inserting the polytef graft with several centimeters of excess length and positioning the axillary anastomosis medial to the pectoralis minor muscle. PMID- 2331222 TI - Hepatic artery reconstruction for hepatic artery thrombosis after orthotopic liver transplantation. AB - We evaluated the efficacy of reconstruction of the hepatic artery for intraoperative or postoperative thrombosis in orthotopic liver transplantation. Of 37 grafts with artery thrombosis, 13 (35.1%, 6 intraoperative and 7 postoperative) underwent reconstruction of the hepatic artery. The arterial flow was reestablished and maintained in 5 (38.5%) of the 13. Recurrent thrombosis in the other 8 grafts developed 2 to 24 days (mean, 13.8 days) after transplantation. Reconstruction was successful in 50% (4/8) of the adults, compared with only 20% (1/5) of the children. Satisfactory results were obtained when a definitive cause of thrombosis could be identified. We conclude that early recognition and correction of the cause of hepatic artery thrombosis during or after orthotopic liver transplantation, especially in adults, is often a graft saving and lifesaving procedure worthy of consideration. PMID- 2331223 TI - Some biomechanical considerations of polytetrafluoroethylene sutures. AB - The biomechanical performance of polytetrafluoroethylene (PTFE) sutures has been compared with that of polypropylene sutures, the standard to which other sutures used in vascular and cardiac surgery are compared. The PTFE is supple and has no plastic memory, while the polypropylene suture is stiff and retains its plastic memory. In addition, the rate of creep encountered in the PTFE suture was significantly less than that of the polypropylene suture. The knotting profiles for knot security for either a square, granny, or surgeon's knot for polypropylene sutures were three throws each. In contrast, knot security with either a square or granny PTFE knot was accomplished with seven throws; six throws were needed for a secure surgeon's knot. The breaking strength of the unknotted and knotted PTFE sutures was approximately one half as great as that for the unknotted and knotted polypropylene sutures. Knot construction significantly reduced the breaking strength of polypropylene sutures but did not alter the breaking strength of PTFE sutures. The percent elongation experienced by both sutures before breakage did not differ significantly. The elasticity, as measured by work recovery, for the polypropylene suture was greater than that for the PTFE suture. On the basis of its unique biomechanical performance characteristics, the PTFE suture should have an important place in vascular and cardiac surgery. PMID- 2331224 TI - Neutrophil activation in acute renal failure and sepsis. AB - Neutrophils are activated during sepsis. To find out whether granulocytes are further activated during hemodialysis with cellulosic and noncellulosic membranes, we compared the plasma levels of the main granulocyte components in patients with chronic uremia who were undergoing regular hemodialysis treatment and patients with acute renal failure with and without sepsis. During hemodialysis with cuprophane dialyzers, plasma-granulocyte elastase, in complex with alpha-proteinase inhibitor, and lactoferrin levels increased in patients who were undergoing regular hemodialysis treatment, but these levels increased further in patients with acute renal failure who did not have sepsis. Maximal neutrophil degranulation was observed in patients with acute renal failure and sepsis. There was only mild degranulation in all three groups during dialysis with dialyzers made of polysulfone. Our data demonstrate that neutrophil activation is increased in patients with acute renal failure, and it is increased further by superimposed sepsis. Cellulose-containing dialysis membranes introduce a further activation of neutrophils. PMID- 2331225 TI - Changes in arterial ketone body ratio in the phase immediately after hepatectomy. Prognostic implications. AB - Postoperative fluctuations of the ketone body ratio in arterial blood (acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox potential, were analyzed in 266 hepatectomized patients in relation to their prognosis. Changes in ketone body ratio were classified into the following two types: a primary decrease at the end of operation and a secondary decrease after transient recovery. Patients were classified into three groups by the primary decrease of ketone body ratio: group 1 (183 cases) with ketone body ratio above 0.7, group 2 (49 cases) between 0.7 and 0.4, and group 3 (34 cases) below 0.4 Ketone body ratio was restored to above 0.7 in 2.5 +/- 0.2 days (mean +/- SE) in all group 2 patients. However, though it was restored within 4.5 +/- 0.4 days in 26 group 3 patients, the other 8 died of multiple organ system failure in 7.4 +/- 2.8 days without recovery of ketone body ratio. This was followed by a secondary decrease in ketone body ratio to below 0.7 in 94 patients, concomitant with complications. The degree of the secondary decrease was positively correlated with that of the primary decrease. In the secondary decrease, of 42 patients with ketone body ratio below 0.4, 28 died of multiple organ failure. Total mortality was 7% in group 1, 12% in group 2, and 50% in group 3. It is suggested that the primary decrease in ketone body ratio at the end of operation is a decisive factor in the prognosis for hepatectomized patients. PMID- 2331227 TI - The possibility of distal embolization from a femoral-popliteal prosthesis above the knee. A consideration against its routine use in this position. AB - The preferential use of a synthetic arterial graft in the above-knee femoral popliteal position is advocated by many surgeons for a variety of reasons. Our recent experience with three cases of substantial deterioration of runoff vessels within a brief period, which may have resulted from embolization from such a conduit, is presented along with other arguments against the routine use of a prosthesis in this position. The procedure with the best possible outcome, namely, one utilizing autogenous vein, should be performed at the outset in all patients except those with a limited life expectancy or those in whom a lengthy procedure would be hazardous. PMID- 2331226 TI - Radioimmunotherapy of human colon cancer in nude mice. AB - Nude mice bearing subcutaneous human colon cancer xenografts (LS174T) were treated with 120 microCi of yttrium 90-labeled anti-carcinoembryonic antigen monoclonal antibodies (specific therapy), 120 microCi of 90Y-labeled anti melanoma monoclonal antibodies (nonspecific therapy), or phosphate-buffered saline solution (no treatment control). Mean (+/- SD) tumor growth rates (percent increase per day) over the first 30 days of the study were as follows: 0.6% +/- 0.2% per day (specific therapy); 17.7% +/- 5.7% per day (nonspecific therapy); and 30.5% +/- 4.2% per day (control). In all three groups, tumors over 1 g had similar doubling times (5.74 +/- 0.71 d). Specific therapy caused a lag in tumor growth corresponding to a 3-logarithm cell kill. Estimated tumor dose of radiation obtained by tissue analysis was 34 and 14 Gy for specific and nonspecific therapy, respectively. In conclusion, 120 microCi of 90Y-labeled anti carcinoembryonic antigen monoclonal antibodies was effective in suppressing growth of human colon cancer xenografts. Clinical studies with this preparation are recommended. PMID- 2331228 TI - Pancreaticoduodenectomy for bleeding periampullary tumors. AB - Periampullary neoplasms with necrosis or ulceration may have potentially troublesome and occasionally life-threatening bleeding. Four patients required pancreaticoduodenectomy for control of bleeding; three had adenocarcinoma of the duodenum and head of the pancreas, and one had an ulcerated carcinoid tumor of the duodenum. In two of these patients, incomplete resection was performed, and in one there was evidence of metastatic disease to the liver. Surgical results were excellent, postoperative courses were benign, and satisfactory palliation was provided. Improving morbidity and mortality with radical resection and aggressive radiotherapy and chemotherapy after surgery with the potential for bleeding from tumor necrosis make resection a reasonable alternative for palliation when localized but advanced disease exists. PMID- 2331229 TI - Nimodipine alters acquisition of a visual discrimination task in chicks. AB - Chicks 5 days old received intraperitoneal injections of nimodipine 30 min before training on either a visual discrimination task (0, 0.5, 1.0, or 5.0 mg/kg) or a test of separation-induced distress vocalizations (0, 0.5, or 2.5 mg/kg). Chicks receiving 1.0 mg/kg nimodipine made significantly fewer visual discrimination errors than vehicle controls by trials 41-60, but did not differ from controls 24 h later. Chicks in the 5 mg/kg group made significantly more errors when compared to controls both during acquisition of the task and during retention. Nimodipine did not alter separation-induced distress vocalizations at any of the doses tested, suggesting that nimodipine's effects on learning cannot be attributed to a reduction in separation distress. These data indicate that nimodipine's facilitation of learning in young subjects is dose dependent, but nimodipine failed to enhance retention. PMID- 2331230 TI - Simple disturbance of the dam in the neonatal period can alter haloperidol induced catalepsy in the adult offspring. AB - Three experiments were performed to determine whether apparently minimal disturbances of dams and litters would influence haloperidol-induced akinesia. In Experiment I, Long-Evans hooded rats (a) were left unmanipulated, (b) received nestcage relocation and observation, (c) received nestcage relocation/observation and maternal separation, or (d) received nestcage relocation/observation and pup handling. The male adult offspring received open-field testing and later received forepaw-on-dowel catalepsy testing following saline, morphine (20 mg/kg), or haloperidol (2 mg/kg). In Experiment II, hooded rats received (a) no manipulation, (b) nestcage relocation, (c) maternal separation, or (d) pup handling. At weaning, dams were tested in the open-field. Activity wheel locomotion of the offspring was assessed following saline or haloperidol for 3 days/week for 3 weeks; then, 5 and 7 days later, rats received haloperidol (0.5 mg/kg) and catalepsy testing. In both experiments, manipulations involving the dam reduced the offsprings' haloperidol-induced catalepsy, but, in Experiment II, a history of haloperidol administration distinguished between the effects of nestcage relocation and maternal separation. In Experiment III, Swiss albino mice received (a) no treatment, (b) nestcage relocation and maternal separation, (c) relocation/separation and mild cold stress of pups, (d) relocation/separation and pup handling, or (e) relocation/separation and severe cold stress of pups. Adult male mice received saline or haloperidol (2.5 mg/kg) and inclined grid catalepsy testing. Mice receiving relocation/separation and mice receiving relocation/separation and severe cold stress showed enhanced catalepsy versus control mice. Thus, it was concluded that seemingly innocuous events in infancy can influence the intensity of extrapyramidal side effects of neuroleptics in adulthood. PMID- 2331231 TI - The effects of pre- and postweaning rearing conditions on latent inhibition and partial reinforcement extinction effect in male rats. AB - Male rats were either handled daily or left undisturbed (nonhandled) during the first 21 days of life. At weaning (Day 22) animals in each early treatment condition were assigned to two housing conditions, isolated or grouped, creating four early/late treatment conditions: Handled-Grouped (HG), Handled-Isolated (HI), Nonhandled-Grouped (NHG), and Nonhandled-Isolated (NHI). At maturity, all animals were tested in the latent inhibition (LI, Experiment 1) and the partial reinforcement extinction effect (PREE, Experiment 2) paradigms. In LI, animals receiving prior nonreinforced preexposure to a stimulus (PE) show subsequently retarded conditioning to that stimulus as compared to nonpreexposed (NPE) controls. In the PREE, partially reinforced (PRF) animals exhibit higher resistance to extinction as compared to continuously reinforced (CRF) controls. LI and PREE were obtained in the HG condition, but were impaired in NHG and HI animals. The pattern of impairment was different in the two conditions. The absence of LI in NHG males was due to increased suppression in the PE group, whereas in HI males, was due to decreased suppression in the NPE group. Likewise, the attenuation of the PREE in NHG males stemmed primarily from decreased resistance to extinction in the PRF group, whereas in HI males, it resulted from increased resistance to extinction in the CRF group. The combination of nonhandling and isolation led to the reinstatement of both LI and PREE: normal LI and PREE were obtained in the NHI animals. These results demonstrate that early rearing experience interacts with later experience differentially depending upon the later experience. PMID- 2331232 TI - Diazepam-stress interactions in the rat: effects on autoanalgesia and a plus-maze model of anxiety. AB - On six occasions spaced at least a week apart, two groups of rats were subjected to a variety of stressful conditions consisting of a restraint/bright light complex, either alone or in combination with a tail pinch, whole-body inversion, or partial immersion in cold water. One of these groups was injected with diazepam (2.0 mg/kg) 30 min prior to the stressors, while the other group experienced the drug in their home cages the following day. A third group also received the diazepam but was not exposed to the stressors. In three test sessions all animals were injected with either diazepam or saline and were then exposed to a novel stressor: a plus-maze used as a screening device for anxiolytic drugs. This was immediately followed by a tail-flick measure of analgesia. The longest tail-flick latencies, indicating stress-induced analgesia ("autoanalgesia"), were observed in the group that had not been exposed to stress prior to testing. The other two groups exhibited substantially shorter latencies but did not differ from one another, thus showing a "stress inoculation" effect that was uninfluenced by diazepam. In the plus-maze, diazepam tends to increase the amount of time rats will spend in the two exposed arms of the maze relative to the two enclosed arms. This effect was significantly attenuated in the group that had previously experienced the variety of stressors after a diazepam injection, suggesting a learned association between drug and stress that resulted in a diminution of the drug's anxiolytic property. PMID- 2331233 TI - Problem solving ability of Octopus vulgaris Lamarck (Mollusca, Cephalopoda). AB - Experiments presented in this study show that Octopus vulgaris Lamarck is able to open transparent glass jars closed with a plastic plug and containing a live crab (Carcinus mediterraneus). The animals remove the plus (Operandum: O) and seize the crab (Predation :P) in one single attack. The number of unsuccessful attacks appears to decrease over a series of trials (p less than .01); during the same period exploration time remains unchanged. There is a statistically significant increase in performance over trials for O (p less than .01) and P (p less than .05) mean times analyzed by single factor ANOVA, suggesting that the learning process is accomplished either by stimulus-response association or by trial and error. We propose that Octopus vulgaris is capable of learning the solutions of both problems, Operandum and Predation, thus showing a highly developed ability of "integration" of the behavioral program. PMID- 2331234 TI - Predictability of chronic intermittent stress: effects on sympathetic-adrenal medullary responses of laboratory rats. AB - This experiment involved an examination of sympathetic-adrenal medullary responses of laboratory rats following exposure to chronic intermittent stress. Animals were assigned at random to one of three groups: (i) controls, handled briefly each day; (ii) restraint stress (RS), restrained for 30 min per day; or (iii) variable stress (VS), exposure to restraint, cold swim, or intermittent footshock during one of five time periods each day. On the 26th day, rats were prepared with chronic tail artery catheters for remote sampling of blood and direct measurement of mean arterial pressure and heart rate. On Day 28, rats of each group were exposed to 30 min of restraint stress and timed blood samples were collected and later analyzed for content of norepinephrine (NE) and epinephrine (EPI). VS rats gained significantly less body weight compared to control and RS rats. Basal measures of blood pressure and heart rate and of plasma NE and EPI were comparable for rats of the three groups. The plasma catecholamine responses to restraint stress on Day 28 were significantly reduced in RS and VS rats compared to first-time stressed controls. These findings suggest that predictability of the type of stressor and the time of its occurrence does not influence the pattern of diminished sympathetic-adrenal medullary responses of animals exposed to chronic intermittent stress. PMID- 2331236 TI - The relationship between infanticide and pregnancy block in mice. AB - Newly pregnant mice are more likely to exhibit pregnancy block when females are exposed to infanticidal males rather than to noninfanticidal males. These data suggest that females are able to assess the risk to their future infants and adjust their reproductive tactic. Those females that did not exhibit pregnancy block in the presence of infanticidal males suffered a greater loss of pups than those in the presence of noninfanticidal males, demonstrating the advantage of pregnancy block. Females served by infanticidal or noninfanticidal males showed no difference in pregnancy block, but if the litter was produced, there was a greater loss of pups sired by infanticidal males. PMID- 2331235 TI - Chronic nicotine and withdrawal effects on radial-arm maze performance in rats. AB - Rats were tested for choice accuracy in an eight-arm radial maze during and after chronic administration of nicotine via subcutaneously implanted glass and Silastic capsules. Nicotine administration significantly improved choice accuracy relative to controls. The effect gradually became apparent over the first 2 weeks of exposure and persisted through the third week. Surprisingly, the significant facilitation of the nicotine-treated rats relative to controls continued for 2 weeks after the end of nicotine administration. No effects of nicotine were seen on choice latency or the strategy to make adjacent arm entries. PMID- 2331237 TI - Long-term effects of preoptic area knife cuts on the maternal behavior of postpartum rats. AB - Knife cuts severing the lateral connections of the medial preoptic area disrupt maternal behavior in postpartum rats. In these studies the knife cuts were produced 1-2 days prior to behavioral testing. The present study examined whether preoptic area knife cuts produce long-term deficits in maternal behavior. Nulliparous Charles River CD rats received knife cuts severing the lateral connections of the medial preoptic area or sham cuts. Approximately 2 weeks later they were mated. All females delivered young 22-23 days after mating, and litter size did not differ between the groups. Females with preoptic knife cuts cleaned their young, built nests (albeit of inferior quality), crouched over their young in a nursing posture, and lactated. The major deficit shown was the near total elimination of retrieval behavior. Females with preoptic knife cuts, however, were capable of performing the oral-motor responses associated with hoarding behavior. These results show that severing the lateral connections of the medial preoptic area does produce long-term deficits in maternal behavior, particularly with respect to maternal retrieving. PMID- 2331238 TI - Long-term spontaneous improvement of performance is related to the strength of the initial training: theoretical implications. AB - In a recent study we established that following a partial acquisition of a brightness discrimination escape task (15 trials), Sprague-Dawley albino rats exhibited a long-term spontaneous improvement of performance (LTSI) after 7 to 14 days. Some evidence suggests a relation between the strength of the initial training and the delay of the optimal retention performance. This study investigates such a possibility in studying performance of rats (number of trials needed to reach a criterion of 10 errorless trials) following nine different retention intervals: 10 min, and 1, 3, 5, 7, 10, 14, 21, and 28 days, after a strengthened initial training (25 trials). Under those conditions, LTSI occurred after a delay of 5 to 7 days. Theoretical implications for an inverse relationship between the strength of initial training and the length of delay leading to LTSI are discussed. PMID- 2331239 TI - A context analysis of contingent teacher attention. AB - The present two-experiment study compared the relationship between on-task student behavior and three measures of contingent teacher attention: total amount, contingent amount, and proportion of the total amount contingent on the target behavior. Toward this goal, a real-time observational system was developed for assessing multiple categories of teacher attention contingent upon a variety of student behavior categories. Using this system, observational data were collected in a self-contained classroom for a mentally retarded adolescent (Experiment 1) and in a remedial summer school classroom for a regular first grade student (Experiment 2). Results from the two experiments showed the proportional measure of contingent teacher attention to account for nearly five times more variance in time on-task than contingent amount. These findings are discussed in terms of the importance of concurrently available teacher attention in the functional analysis of classroom behavior. PMID- 2331240 TI - Teaching adolescents with severe disabilities to use the public telephone. AB - Two adolescents with severe disabilities served as participants in a study conducted to train in the use of the public telephone to call home. Participants were trained to complete a 17-step task analysis using a training package which consisted of total task presentation in conjunction with a four-level prompting procedure (i.e., independent, verbal, verbal + gesture, verbal + guidance). All instruction took place in a public setting (e.g., a shopping mall) with generalization probes taken in two alternative settings (e.g., a movie theater and a convenience store). A multiple probe across individuals design demonstrated the training package was successful in teaching participants to use the telephone to call home. In addition, newly acquired skills generalized to the two untrained settings. Implications for community-based training are discussed. PMID- 2331241 TI - Resistance during psychotherapy and behavior therapy. AB - The purpose of the present study into the phenomenon of resistance was twofold. First, the meaning of the concept as conceived by therapists of psychoanalytic and behavioral orientation was investigated. Second, an attempt was made to gain insight into the dynamics of the clinical phenomenon of resistance. The results of the study indicated that both groups of therapists attached virtually the same meaning to the concept of resistance. Both groups viewed the same classes of behaviors as indicative of resistance. Furthermore, it was found, as expected, that analytically oriented therapists reported the occurrence of resistance more frequently. The two groups agreed that "avoiding" and "fighting" behaviors were the most prominent resistances of clients. Therapist behaviors that were most likely to elicit resistance in the client are the "informative" behaviors, such as asking questions about the nature and origin of the complaint. Clinical implications of the research findings are discussed. PMID- 2331242 TI - Effects of two error-correction procedures on oral reading errors. Word supply versus sentence repeat. AB - The effects of two error-correction procedures on oral reading errors and a control condition were compared in an alternating treatments design with three students who were moderately mentally retarded. The two procedures evaluated were word supply and sentence repeat. The teacher supplied the reader with the correct word immediately after each student error during the word-supply condition. During the sentence-repeat condition, the teacher supplied the correct word immediately after each student error, required the student to repeat the correct word, complete reading the sentence, and then reread the entire sentence. Both word-supply and sentence-repeat procedures were effective in reducing oral reading errors when compared to a no-intervention control condition, but sentence repeat was superior to word supply. In addition, a similar relationship was found between the two procedures when the students were tested for retention on the same reading passages a week later. These results show that sentence repeat is more effective than is the commonly used word-supply procedure in remediating the oral reading errors of students with moderate mental retardation. PMID- 2331243 TI - BVP-biofeedback in the treatment of migraine. The effects of constriction and dilatation during different phases of the migraine attack. AB - Biofeedback training for self-regulation of blood-volume pulse ("BVP") amplitude of the temporal arteries has been used previously with good results in treatment of migraine headaches. In the present study, 23 subjects were randomly assigned to one of three groups and given (a) biofeedback training in temporal artery constriction and instructions to apply these skills during headaches; (b) the same training and instructions to apply the skills between headaches, during stress periods, and (c) biofeedback training to dilate the temporal arteries, and instructions to use these skills during stress periods. Clinically meaningful headache reductions were achieved and maintained at follow-up. Furthermore, results indicated that voluntary temporal artery dilatation also leads to headache reductions, and that there is a connection between levels of achieved self-regulation skill and the clinical effects. PMID- 2331244 TI - [Development of infestation with Varroa jacobsoni O. in bee colonies in Tunisia]. AB - The mite Varroa jacobsoni, an ectoparasite of the honey bee, was imported to Tunisia probably in 1976. Afterwards, this parasitosis caused severe losses of colonies for several years. The continued examination of the level of infestation in colonies of a "GTZ" project stated a steady number of mites since 1980. Only in a few colonies, the infestation was above the limit of damage. Though the colonies in North West Tunisia did not receive any treatment since 1986 there was no increase of infestation. In order to investigate the reason for this the mites' ability of reproduction was examined during two following years. The portion of infertile female mites in the worker brood in most of the colonies was with 50% considerably higher than in Europe. In Brazil, the adaptation between host and mite produced similar low reproduction rates. As, however, in Tunisia the portion of infertile females in the drone brood of the individual colonies corresponded to the one in the worker brood climatic conditions are supposed to be responsible. PMID- 2331245 TI - [The adaptation of the morphometric parameters of fat cell size for the purposes of animal science research. 2. Cellularity of subcutaneous adipose tissue of different swine breeds influenced by graduated feed levels and in relation to metabolic data and parameters of body fat degeneration]. AB - Measurements of morphological and biochemical parameters in subcutaneous adipose tissue as well as investigations of energy metabolism and fat deposition of 89 male castrated pigs were performed. Breeding lines of swine (German Landrace) had been selected through 8 generations for high ("E(+)-Line") and low ("E(-)-Line") levels of NADPH-generating dehydrogenases. A control group ("K.") without selection was closely paralleled. For 21 days the animals were kept under feeding experiments within 2 sectors of growing period (67 kg, 85 kg body mass), and biopsies of backfat were examined subsequently. The inner layer of subcutaneous adipose tissue showed constantly bigger fat cells than the outer layer. The fat cell size increased generally with fattening and body mass respectively. The cellularity of adipose tissue was dependent significantly on the percentage of the very small fat cells measured up to 30 microns diameter (= "PKF30"). The breeding lines differed slightly with respect to their cellularity: The inner layer showed the gradation E+ greater than K. greater than E- concerning fat cell volumes and fat cell surfaces respectively. The PKF30 correlated significantly with food energy level as well as with the respirationally examined protein retention, particularly in inner layers of younger animals. Relations to the fat deposition (examined respirationally or with the D2O-Method and after slaughter respectively) were recognized, not showing validity for all cases. The parameters of lipogenic activity tested by tissue slice preparations and homogenates respectively correlated negatively with average fat cell size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331246 TI - [The use of a test model in a stepped form (test steps) for the clarification of different problem situations in X-ray diagnosis. 2. The use of test steps for testing the POLAROID-TPX immediate X-ray picture system]. AB - The stepwedge, described in part 1 and in other publications, was used for the examination of the POLAROID-Instant Radiographic System. The result showed, that this system is a quite acceptable method for the practitioner. POLAROID radiographs, in comparison with the classic radiographs, show equal contrast and detail-visibility, but demand a higher radiation dose. PMID- 2331247 TI - [Pilot study of the practicability of a commercially-available Salmonella rapid test for the detection of the Salmonella content of cattle fecal samples]. AB - 100 faeces samples of cattle were investigated in comparison to a recent commercially available Salmonella Rapid Test (OXOID) and a cultural standard method (non-selective enrichment in buffered peptone water, selective enrichment in RAPPAPORT-VASSILIADIS-medium) for presence of Salmonella. The Salmonella Rapid Test showed in positive results an accuracy ("sensitivity") of 94.7% and in negative results an assurance ("specificity") of 97.5% and is therefore suitable for rapid detection (within 2 days) of faeces sample of cattle with Salmonella. PMID- 2331248 TI - The clinical significance of predictions based on screening second trimester mean arterial pressure: adverse maternal [corrected] and infant outcomes. AB - The design of a trial of primary prevention of hypertension in pregnancy rests on both the ability to identify women who are at risk and the definition of a clinically important outcome. The risk of developing antepartum hypertension can now be assessed nonivasively by the midpoint of pregnancy. However, maternal hypertension is not always associated with a clinically important adverse outcome for either mother or infant. The purpose of this study was to prospectively assess whether increasing risk of antepartum hypertension is associated with increasing rates of clinically important maternal and/or infant morbidity. We assembled a prospective cohort of 720 women with singleton pregnancies. The proportion of pregnancies complicated by both antepartum hypertension and maternal and/or infant morbidity increased significantly between low, moderate, and high risk groups (0.2, 6 and 58.8%, respectively, p less than 0.0001). We conclude that a trial of primary prevention of hypertension in pregnancy should include a measure of significant morbidity in mother and infant. PMID- 2331249 TI - Elevated blood cholesterol. A risk factor for coronary heart disease. AB - 1. The Report of the Adult Treatment Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults is designed to provide guidance to healthcare professionals in the detection, evaluation, and treatment of adult hypercholesterolemic patients. 2. Dietary intervention, an essential part of every treatment plan, is highlighted followed by the introduction of drug treatment if the dietary intervention fails to achieve the desired results. 3. Guidelines for intervention at the worksite, including those using community resources, are discussed. PMID- 2331250 TI - Cholesterol education at the worksite. AB - 1. Risk factors for coronary heart disease include age, sex, family history, high cholesterol, blood pressure, smoking, and severe obesity. The last four risk factors can be modified with lifestyle changes. 2. Occupational health nurses who provide primary care to workers can assist employees in detecting and treating their elevated cholesterol. Cholesterol screening at the workplace is an effective means for employees to learn their cholesterol level or monitor their dietary progress in lowering their cholesterol. 3. Employees can modify their eating behaviors by developing the skills to make wise dietary choices. Simple dietary self assessment and self monitoring tools will aid employees in monitoring and evaluating their efforts. 4. To successfully implement a cholesterol education program and counsel employees, occupational health nurses need to increase their knowledge of nutrition, specifically the composition of a diet that will help reduce the risks associated with heart disease. PMID- 2331251 TI - Diet and drug therapy for hypercholesterolemia. Principles and perspectives for the occupational health setting. AB - 1. Most individuals with moderately elevated blood cholesterol can lower their cholesterol significantly by following a low fat, low cholesterol diet, which is the first step in the treatment of hypercholesterolemia. 2. The standard low fat, low cholesterol diet recommended by the American Heart Association and the National Cholesterol Education Program restricts total fat intake to less than 30% of calories, with 10% derived from each of the three types of fats (saturated, polyunsaturated, and monounsaturated); and dietary cholesterol to less than 300 mg per day. 3. A client whose LDL cholesterol remains elevated after 6 months on the low fat, low cholesterol diet should be considered a candidate for drug therapy. New guidelines from the National Cholesterol Education Program are now available to assist in selecting the appropriate cholesterol lowering drug for clients with high risk hypercholesterolemia. 4. The current national guidelines for treating hypercholesterolemia offer occupational health nurses new opportunities for teaching risk reduction in the workplace. PMID- 2331252 TI - Evaluation of an employee health risk appraisal program. AB - 1. After 2 years of employee participation, a computerized health risk assessment program managed by occupational health nurses was evaluated to determine whether health risk factor levels had undergone any significant change. 2. Data on 387 hospital employees were examined. Statistically significant reductions in risk factor levels were found for diastolic blood pressure, serum cholesterol, and smoking. The risk factor "weight" remained unchanged from year 1 to year 2 for both groups. 3. These findings suggest that the nursing interventions of focused, written feedback on risk factors, private counseling, and risk reduction education classes may have been important in motivating employees to make significant lifestyle changes. PMID- 2331253 TI - Computerized information management. Part II: Hardware and software--making the right choice. PMID- 2331254 TI - Public health in the workplace. Part III: Health and safety trends. PMID- 2331255 TI - Comparison of intraosseous versus intravenous loading of phenytoin in pigs and effect on bone marrow. AB - Much recent literature supports the resurgence of the intraosseous route of access in pediatrics. Intraosseous lines provide a timely noncollapsable route to the circulation in medical or traumatic emergencies when intravenous access is not possible. There has been no controlled study comparing intravenous and intraosseous loading of phenytoin. A 15 mg/kg dose of phenytoin was administered over 15 minutes to pigs by either the intravenous (n = 6) or tibial intraosseous route (n = 6). Femoral artery blood samples were drawn every 5 minutes for 35 minutes after initiation of infusion to determine phenytoin levels. There was no statistical difference between the two groups using analysis of variance repeated measures (P = .160). Microscopic examination of the cortex and marrow at the intraosseous site in these pigs was normal 5 weeks postinfusion. The authors conclude that the intraosseous route is an effective alternative to intravenous loading of phenytoin without permanent damage to the marrow. PMID- 2331256 TI - High pressure percutaneous transtracheal ventilation: the use of large gauge intravenous-type catheters in the totally obstructed airway. AB - Percutaneous transtracheal ventilation using a large gauge intravenous-type catheter can be used successfully in the setting of complete upper airway obstruction in animals. In this study, using a large animal model, satisfactory oxygenation and ventilation was achieved by inversely varying the catheter size and the inspiration to expiration ratio (I:E). Specifically, 30 to 63 kg ruminants with an obstructed upper airway were resuscitated for 30 minutes from a hypoxic, hypercarbic, and acidotic state using 12- and 14-gauge catheters connected to a 50 psi oxygen source via a two-way valve with an I:E of 1:4 and 1:9 seconds, respectively. Shorter expiratory time or increased inspiratory time with these intravenous catheters resulted in significant hemodynamic compromise, barotrauma, inadequate carbon dioxide elimination, acidemia, and frequent death. PMID- 2331257 TI - The effect of bolus injection on circulation times during cardiac arrest. AB - Previous investigations have shown that peripheral injection of medication during cardiac arrest leads to prolonged circulation times and low peak drug levels. Current Advanced Cardiac Life Support guidelines suggest that administering a bolus of flush solution after injection of medication may hasten drug delivery, but there is little evidence to support this. The purpose of this study is to investigate the effect of peripheral bolus injection on circulation times during cardiac arrest. Measurements of circulation times were made following injection of indocyanine green dye both with and without a bolus of 20 mL saline flush into a peripheral vein of mongrel dogs. There was no difference in systolic, diastolic, or coronary perfusion pressures during the injections with or without bolus injection. Similarly, there was no difference in end-tidal CO2 or in arterial-venous PO2, PCO2, or pH gradient. The circulation time without bolus injection was 77.7 +/- 42.7 seconds while circulation time with the saline flush was 48.3 +/- 20.9 seconds (P less than .001). Peak dye concentration without saline flush was 3.0 +/- 1.0 mg/L, and peak dye concentration with saline flush was 3.8 +/- 0.9 mg/L (P less than .001). We conclude that a bolus injection of 20 mL of saline enhances dye circulation times and peak levels during cardiac arrest in this animal model. The clinical application of this technique warrants further investigation. PMID- 2331258 TI - Formula for emergency physician staffing. AB - Estimates of emergency physician needs traditionally have relied on calculations based on the number of patients seen by the emergency physician (volume formula). We have found this model has not predicted accurately manpower needs in our emergency department as the case mix of services has changed. The "LIVES" formula estimates the amount of time emergency physicians provide services by using Length of stay, intensity of services, and Service type in addition to the traditional factors (Volume of patients, Efficiency of physicians). Thirteen years of statistics from our emergency department were used to examine the performance of the two formulas in predicting changes in the amount of physician services. The LIVES formula performed better than the volume formula: a better fit with number of physicians used by chi 2 analysis (chi 2 = 1084 versus 5591), a better correlation with physicians used (regression coefficient 0.98 v 0.21), a higher degree of association with physicians used (correlation coefficient 0.96 versus 0.53 with P less than 0.0001 v 0.06 by Student's t-test), and explained more of the variability in the amount of physicians used (92% v 28%). Changes in types of services provided by the modern emergency department require multifactorial analysis to determine manpower needs. PMID- 2331259 TI - Simultaneous epiglottitis and parotitis: a case report. AB - A patient presenting to the emergency department with simultaneous parotitis and epiglottitis is described. She underwent emergency airway intervention within 3 hours of presentation. This is the first case of simultaneous parotitis and epiglotitis. Diagnostic symptoms are discussed. PMID- 2331260 TI - Chronic cocaine abuse associated with dilated cardiomyopathy. PMID- 2331261 TI - Tension hydrothorax and shock in a patient with a malignant pleural effusion. AB - A patient presented to the emergency department with a malignant pleural effusion associated with shortness of breath, and radiographic evidence of mediastinal shift and hypotension. Tube thoracostomy yielded serosanguinous pleural fluid under pressure and after 1 liter of fluid was drained, the patient's hemodynamic status stabilized. The entity of tension hydrothorax is rare but may be life threatening. The treatment should consist of prompt drainage and efforts to prevent recurrence. As physicians become more adept at prolonging the lives of patients with cancer, tension hydrothorax may become more common. PMID- 2331262 TI - The toddler's fracture revisited. AB - The authors have reviewed our experience with 37 cases of toddler's fracture. This fracture of the distal tibia occurs in 1 to 4 year-old-children. History of trauma is usually trivial and the physical findings and radiological appearance are often subtle. The latter consists of a faint oblique lucent line crossing the distal tibia and terminating medially. It is usually seen on the anteroposterior view, poorly seen on the lateral and well seen on the internal oblique. Initial radiographs may be normal. A similar fracture of the midshaft of the tibia was associated with child abuse. Treatment consists of immobilization for a few weeks to protect the limb and to relieve pain. Diagnosis requires a high index of suspicion and is important because it obviates the need for investigations to rule out more sinister etiologies such as tumor or infection. The finding of a midshaft tibial fracture may indicate child abuse. PMID- 2331263 TI - Traumatic asphyxia: an indicator of significant pulmonary injury. AB - Traumatic asphyxia has often been described as a rare syndrome with little prognostic significance. In the authors' series, however, all cases secondary to deceleration injury or compression of the anterior thorax were associated with pulmonary injury. The signs of venous congestion of the face and anterior thorax are not always recognized in the emergency department where they should be most clinically evident. Increased awareness of this syndrome by emergency physicians will result in better reporting and understanding of its clinical implications. PMID- 2331264 TI - Spiral tibial fractures of children: a commonly accidental spiral long bone fracture. AB - Pediatric training in child abuse has consistently emphasized a strong association between nonaccidental injuries and spiral fractures of long bones. Isolated spiral tibial fractures of childhood have previously been recognized by the orthopedic specialty to most frequently be accidental in etiology. The authors present evidence that supports a predominantly accidental etiology for isolated spiral tibial fractures of young children. This article presents a series in which 9 of 10 such spiral fractures were most likely the result of an accident and not child abuse or gross neglect. Additionally, almost all of these fractures presented as a gait disturbance and should be included in the differential of this complaint. PMID- 2331265 TI - Cases in electrocardiography. PMID- 2331266 TI - Ethchlorvynol overdose. AB - Ethchlorvynol remains a drug that frequently surfaces in clinical emergency practice despite safer and more effective pharmaceutical agents on the market. Effects such as poisoning, dependence, ocular damage, and overdose continue to receive attention in the literature. Awareness of complications and treatment in ethchlorvynol exposure requires attention to a drug remaining clinically available without an appropriate clinical indication. PMID- 2331267 TI - The elderly and emergency medicine. PMID- 2331268 TI - A practical method of teaching emergency intraosseous infusions. PMID- 2331269 TI - Effectiveness of midazolam as a sedative for cardioverting patients with tachydysrhythmias in the awake state. PMID- 2331270 TI - In utero resolution of hydrops fetalis following the death of one twin in twin twin transfusion. AB - A case of massive hydramnios involving a twin-twin transfusion syndrome is presented with death of the larger twin and the development of hydrops fetalis in the surviving smaller twin. The amniotic fluid volume of the surviving twin became normal and the hydrops fetalis resolved spontaneously in utero. Concomitant with the resolution of the hydrops fetalis, the umbilical cord systolic to diastolic ratio improved. At the time of delivery, the hydrops had resolved. The liveborn infant died 11 days later secondary to pulmonary hypertension and cardiorespiratory failure. Although the fetal status improved in utero, the pulmonary hypertension postdelivery resulted in neonatal death. PMID- 2331271 TI - Tolerance of fat emulsions in very low birthweight neonates: effect of birthweight on plasma lipid concentrations. AB - Plasma concentrations of various lipid fractions (total lipids, free glycerol, true triglycerides, free fatty acids, and cholesterol) were studied in 20 normally grown neonates ranging in birthweight from 820 to 1500 gm and in gestational age from 28 to 34 weeks. They were subdivided into three weight categories: 750 to 999, 1000 to 1249, and 1250 to 1500 gm. A lipid emulsion was infused at a constant rate over 24 hours, beginning with an hourly infusion rate of 0.04 gm/kg and increasing each day by 0.04 gm/kg up to a maximum of 0.16 gm/kg. Neonates who weighed less than 1000 gm had higher mean plasma concentrations of total lipids and free glycerol at hourly infusion rates of 0.08 and 0.16 and of triglycerides and free fatty acids at hourly infusion rate of 0.16 gm/kg than their heavier peers. These data suggest that extreme caution be used when administering parenteral fat emulsions to neonates who weigh less than 1000 gm and that we need to monitor plasma closely for signs of hyperlipemia. PMID- 2331272 TI - Renal responses to immersion and exercise in pregnancy. AB - Twelve healthy pregnant women were studied at 15, 25, and 35 weeks' gestation and at 8 to 12 weeks postpartum. Women were immersed for 20 minutes at 30 degrees C. They then exercised at 60% maximum oxygen capacity on a modified ergometer. Substantial diuresis and natriuresis occurred without changes in osmolarity or serum sodium. The diuresis was significantly greater during pregnancy than postpartum. The natriuresis was similar. Diuresis and natriuresis were greater than would be expected from investigations in nonpregnant subjects. This study suggests that immersion may be a beneficial therapy for edema without decreasing plasma volume. PMID- 2331273 TI - Plasma levels of fibronectin and prostacyclin metabolite in peripartum preeclamptic women. AB - Plasma fibronectin and prostacyclin levels have been reported to vary in preeclamptic women when compared with pregnant control women. Elevation of fibronectin and deficiency of prostacyclin have been postulated to be due to endothelial cell disruption or dysfunction. Eighteen preeclamptic women and 19 normal pregnant controls were evaluated for plasma levels of fibronectin and the prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). 6-keto PGF1 alpha and fibronectin plasma levels in patients were significantly different from control patients, with preeclamptic patients exceeding control subjects. Five patients had serial samples of 6-keto-PGF1 alpha prior to, during, and after intravenous magnesium sulfate therapy and no consistent effect was noted. No correlation existed between fibronectin and 6-keto-PGF1 alpha levels or between either compound and platelet count or liver function tests. Despite an overall elevation of fibronectin in preeclamptic patients, two patients with the hemolysis, elevated liver tests, and low platelet count syndrome showed low normal fibronectin levels coinciding with thrombocytopenia, hemolysis, and liver dysfunction. The magnitude of fibronectin elevation may therefore not predict the severity of preeclampsia. The significance of these findings is discussed. PMID- 2331274 TI - Leukocyte esterase activity in amniotic fluid: normal values during pregnancy. AB - Chorioamnionitis during pregnancy is a common diagnostic dilemma for the obstetrician. Fast and accurate diagnosis poses the most significant problem. Since leukocytes are known to be released in response to infections, examination of amniotic fluid for their presence is an important part of the evaluation for chorioamnionitis. These neutrophils contain several esterases that are not present in serum, urine, or vaginal secretions. The esterases are not influenced by bacteria or by commonly used drugs. We have previously described the reliability of leukocyte esterase (LE) activity for the detection of chorioamnionitis in term pregnancies uncomplicated by other diseases. A prospective study was performed to assess the presence or absence of LE activity to establish normal values in amniotic fluid at various gestational ages prior to term before its use as a possible predictor for chorioamnionitis. Sterile amniotic fluid specimens were obtained from 13 patients undergoing second trimester genetic amniocentesis (with gestational ages varying from 15 to 19 weeks) and from 11 patients with a wide variety of medical problems, undergoing amniocentesis for Rh sensitization or lung maturation studies (with gestational ages ranging from 25 to 27 weeks). All patients with ruptured membranes or preterm labor were excluded. Each amniotic fluid sample was divided into two parts, one of which was transported to the laboratory for aerobic and anaerobic cultures and the other used for LE activity detection as measured by dipstick. The LE results were retrospectively compared with the results of the cultures. LE activity was always found to be negative when the culture results were negative. negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331275 TI - Relationship between renal histology and plasma antithrombin III activity in women with early onset preeclampsia. AB - Renal biopsy was performed in 12 women with the clinical diagnosis of severe, early-onset preeclampsia at the time of cesarean delivery for the express purpose of aiding future counseling on the risk of recurrence. The mean gestation at delivery was 30 +/- 3 weeks. The mean birthweight was 1090 +/- 505 gm. Four women (33%) were multiparous. Antithrombin III activity was determined immediately prior to delivery unrelated to clinical care and as part of other protocols. The biopsy was performed without difficulty in each, although the sample was inadequate in one patient. The clinical diagnosis of preeclampsia was confirmed in nine (82%). However, three of the nine had underlying renal disease, as did the two women without histologic evidence of preeclampsia (42% of the total). Correlations between laboratory parameters with the histopathologic diagnoses were sought. Neither uric acid, creatinine, blood urea nitrogen, platelet count, or 24-hour urinary protein measurements aided the differentiation of the various subgroups. Antithrombin III activity in women with biopsy-supported preeclampsia (77% +/- 12%) was significantly lower than that in women without histologic evidence of preeclampsia (116% +/- 8%). Antithrombin III activity correctly predicted biopsy findings in at least 9 of 11 (82%). These preliminary findings confirm the high frequency of underlying disease in women with early-onset preeclampsia. Although low antithrombin III activity does not differentiate between "pure" preeclampsia and superimposed disease, a normal antithrombin III activity is reassuring and more consistent with a nonpreeclamptic renal complication than with preeclampsia. PMID- 2331276 TI - Oral bretylium tosylate use during pregnancy and subsequent breastfeeding: a case report. AB - A 39-year-old woman with long QT interval syndrome received chronic oral bretylium tosylate during pregnancy and subsequent breastfeeding. The pregnancy and delivery were uncomplicated and no side effects have been observed in the infant. PMID- 2331277 TI - Evaluating the quality of perinatal health care. AB - 1. The quality of perinatal health care is indirectly evaluated by determining the PNM rate. 2. The standardized PNM rate is a useful index to identify perinatal care facilities that need further review by perinatal mortality audit. 3. Long-term follow-up is needed to determine if decreasing mortality by obstetric interventions is accompanied by a beneficial effect on the surviving infants or by an increase in morbidity. 4. In the near future, mortality and severity of illness data will be required for hospital accreditation. 5. The present challenge is to contain costs without lowering the quality of care. PMID- 2331278 TI - Magnesium sulfate and intrapartum fetal behavior. AB - The effect of magnesium sulfate (MgSO4) in intrapartum fetal behavior as judged by heart rate cyclicity was investigated by comparing the fetal heart characteristics of 15 term fetuses whose mothers received MgSO4 with a control group of 54 healthy term fetuses whose mothers received no antepartum medications. The duration of different fetal heart cycles and percentage of time spent in a particular cycle except for cycle C (6 to 10 beats per minute) were not different between groups. Seventy-seven percent of fetuses of the study group versus 24% of fetuses in the control group exhibited markedly diminished variability (cycle A) and 8% versus 63%, respectively, experienced cycles of increased variability (cycle D). Our observations may explain the conflicting conclusions of previous reports regarding the affect of MgSO4 on fetal heart rate variability. PMID- 2331279 TI - Improved survival and neurodevelopmental outcome for infants less than 801 grams birthweight. AB - We reviewed the perinatal management and subsequent outcome of infants 401 to 800 gm birthweight delivered in 1983 to 1985 compared with those born in 1980 to 1982. Intrapartum fetal heart rate monitoring, cesarean section delivery, attempted delivery room resuscitation, and 5-minute Apgar scores greater than 5 were more frequent in 1983 to 1985. Significantly greater neonatal survival was evident for infants 500 to 700 gm birthweight (31%) and 24 to 27 weeks' gestation (45%) in 1983 to 1985, p less than 0.005. Infant birthweight, gestational age, gender, and 5-minute Apgar score, in addition to intrapartum tocolysis use, were predictors of higher survival by stepwise discriminant analysis. At a mean follow up of 27 months, 13% (6 of 46) born in 1983 to 1985 had major disability compared with 67% (6 of 9) of infants born in 1980 to 1982. There has been a significant increase in survival and improvement in neurodevelopmental follow-up status for infants less than 801 gm birthweight. These improved outcome data should be considered by caregivers providing perinatal management and counseling parents regarding extremely low birthweight infants. PMID- 2331280 TI - Ambulatory uterine activity monitoring in the post-hospital care of patients with preterm labor. AB - Care of women with preterm labor has been reported by Katz et al to be enhanced by use of an electronic uterine contraction monitor. We enrolled 76 women with singleton gestations who had been successfully treated for preterm labor into a prospective randomized trial, assigning subjects in a ratio of 1:2 to a group of 27 receiving education and self-palpation (EP) or to a group of 49 receiving education and an ambulatory monitor (EM). Subjects in both groups received an intensive education session at entry and were contacted frequently (5 days/week in EP and daily in EM) thereafter to report symptoms and frequency of contractions. Physicians were advised to adjust the dosage of oral tocolytic to maintain fewer than four contractions per hour. Rates of recurrent preterm labor and preterm delivery did not differ between the groups. Although the sample size in this study is too small to exclude entirely the possibility of alpha error, our inability to demonstrate a difference suggests that the improvement reported by others in pregnancy outcome associated with use of an electronic ambulatory contraction monitor may be the result of daily attention to symptoms and signs of preterm labor. PMID- 2331281 TI - Changing diagnosis of cerebral palsy in very low birthweight children. AB - The stability of the diagnosis of cerebral palsy from 2 to 5 years of age was examined in 83 children of birthweight under 1000 gm, and 112 of birthweight 1000 to 1500 gm. In 20 2-year-old children with cerebral palsy, the diagnosis persisted in 11 (55%, 95% confidence intervals 35.1 to 76.9%); 2 of 175 children (1.1%) free of cerebral palsy at 2 years of age subsequently developed the condition. Severe or moderate cerebral palsy at 2 years persisted in all eight children (100%). In 9 of 12 children in whom cerebral palsy at 2 years had disappeared by 5 years, minor neurologic abnormalities and left-hand preference occurred frequently but mean psychologic tests scores were similar to children always free of cerebral palsy. In this cohort, cerebral palsy at 2 years was not a static condition, but overestimated later prevalence. PMID- 2331282 TI - Hemodynamic changes in a term newborn piglet model of patent ductus arteriosus. AB - Patent ductus arteriosus (PDA) is a common form of congenital heart disease in full-term infants. To investigate the morbidities associated with a left to right PDA shunt, we produced a PDA in six full-term newborn piglets (less than 36 hours old) by bathing the ductus arteriosus with prostaglandin E (PGE) and infiltrating it with formalin. In five age-matched piglets, the ductus arteriosus was ligated to serve as controls. Microsphere determinations of left ventricular output (LVO) and regional blood flow (Q) were made on three consecutive days. We produced left to right shunts of 36 to 47% (mean) in the experimental piglets. The experimental piglets had a 22 to 36% increase in LVO with a one- to twofold reduction in percentage of LVO to the kidneys and carcass (p less than 0.05). Although percentage of LVO to the gastrointestinal tract was reduced (p less than 0.05), no reduction of absolute Q to the gastrointestinal tract was observed. Brain and heart Q were similar in both groups. We conclude that significant hemodynamic changes result from left to right shunting in the full-term newborn piglet with PDA. These hemodynamic changes, such as reduction in renal blood flow, are relevant information that will help explain the morbidities observed in infants with a hemodynamically significant PDA with a left to right shunt. PMID- 2331283 TI - Does pregnancy alter the rate of progression of diabetic nephropathy? AB - The effect of gestation on the rate of decline in renal function was studied in 11 pregnancies complicated by diabetic nephropathy. For each pregnancy, serum creatinine levels were available within 4 years before pregnancy, during pregnancy, and within 4 years after delivery. Although all of these patients were hypertensive and had increased proteinuria during pregnancy, the mean serum creatinine just prior to conception (1.3 +/- 0.5 mg/dl) and the last follow-up value (1.2 +/- 0.3 mg/dl) were not significantly different. When the inverse of serum creatinine (1/Scr) was used to estimate creatinine clearance, the renal function was either improved or remained stable in the majority of the pregnancies (7 of 11). The observed decline in renal function through the end of follow-up appeared to be consistent with the expected natural course of diabetic nephropathy in the absence of pregnancy. Furthermore, the slope for inverse serum creatinine before and after pregnancy was not significantly different. In conclusion, pregnancy in patients with mild to moderate diabetic nephropathy does not seem to accelerate the rate of decline in renal function. PMID- 2331284 TI - Closure of a rapidly exchanging calcium compartment in rat cardiac myocytes by lanthanum. AB - Enzymatically isolated myocytes from adult rats were used to measure 45Ca-uptake from salt media of reduced Ca2(+)-content (0.1 mM) with normal (4 mM) or elevated (20 mM) potassium concentrations. Ca2(+)-uptake was interrupted by filtration followed by rapid chasing the filter with salt solutions containing no Ca2+, 2 mM Ca2+ or 2 mM La3+. Rate and extent of 45Ca-uptake of resting cells were found to be 3-fold enhanced when chasing was performed with La3(+)-containing media. In contrast La3+ does not affect Ca2(+)-exchange of depolarized cells, the fluxes of which approximate rates sufficiently high for contraction activation and that are sensitive to Ca2(+)-channel blockers. The effect of La3+ on resting cells suggests the existence of a small rapidly exchanging La3(+)-sensitive Ca2(+) compartment located adjacent to the plasma membrane. This compartment is though to be either closed or has become La3(+)-insensitive in activated cells. The subsarcolemmal cysternae of the SR, the so-called "peripheral couplings" are most likely the morphological substrate of this compartment. PMID- 2331285 TI - Carbohydrate tolerance status in patients with myocardial infarction. AB - Hyperglycemia is an important independent risk factor in the development of coronary artery disease. Sixty one patients suffering from chronic and acute myocardial infarction out of which 12 patients were diabetic and 10 normal control subjects were investigated. The patients without diabetes and control subjects were subjected to oral and intravenous glucose tolerance tests. It was observed that the post load glucose level of most of the patients and fasting insulin level of patients without diabetes were higher as compared with control subjects. From the intravenous glucose tolerance test, half life of glucose and glucose assimilation coefficient were determined. Half life of glucose was increased significantly and glucose assimilation coefficient was decreased in the patients with myocardial infarction as compared with those of control subjects. The observations confirm that carbohydrate intolerance in myocardial infarction is not due to suppression of insulin secretion but due to peripheral utilization. PMID- 2331286 TI - Hydrophilic interactions between charged amino acids and the effect of ions on the strength of interaction. AB - The interaction between oppositely charged amino acids was studied by charge transfer reversed-phase thin-layer chromatography. The dependence of the lipophilicity of Arg, Lys and Orn on the concentration of Glu, Asp, Gln and Asn in the eluent was considered to be related to the strength of interaction. The interaction of dibasic amino acids with Glu and Asp was stronger than with Gln and Asn. Mono- (Li+, Na+, K+, Rb+ and Cs+) and divalent (Mg2+ and Ca2+) cations decreased the strength of interaction suggesting the electrostatic character of the interaction. Their inhibitory effect mainly depended on their concentration and to a lesser extent on the ion charge and hydrated ion radii. Stepwise regression analysis proved that the strength of interaction depends on the polarity parameters of amino acids and is independent of their chemical structure. PMID- 2331287 TI - Situational characteristics of safety belt use. AB - Past research concerning the use and nonuse of safety belts has tended to stereotype users and nonusers as distinct entities on the basis of a single observed situation. The thought processes underlying the reasons given by drivers for using or not using seat belts have not been explored. The purpose of this study was to observe belt use by a group of drivers and describe factors contributing to their use or nonuse as defined by the drivers themselves. In depth interviews were undertaken with 239 drivers whose safety belt wearing behavior was observed in specific city or highway driving locations. Vehicle license numbers, gender, and age group of selected drivers were used to retrieve driver records and insurance policy data. Open-ended questions were asked concerning their reasons for use or nonuse and their attitudes towards safety belts and other types of traffic safety countermeasures. Driver attitudes, characteristics, and records were compared between observed safety belt user and nonuser groups to validate variables predicting use or nonuse. Respondents' descriptions of the social and personal context of their choice to use or not use safety belts provide a broader view of seat belt wearing that suggests implications for planning future enforcement and education programs. PMID- 2331288 TI - Age dependence of attitudes and knowledge in cyclists. AB - A number of factors related to bicycle accidents were studied, namely, knowledge of priority rules, attitude and self-reported behavior regarding traffic rules, and general opinions about the safety of the traffic behavior of cyclists and drivers. In order to get an indication of the influence of these factors at different stages of the life span, subjects ranging from 9 to 83 years of age were represented in the study. The relationship between age and the various measures was found to be U-shaped in most cases. The older cyclists and the 9 to 11 year olds, the two groups that are most at risk, were deficient regarding knowledge while showing the most positive attitudes. Implications with respect to possible counter measures are discussed. PMID- 2331289 TI - The effects of the new 65 mile-per-hour speed limit on rural highway fatalities: a state-by-state analysis. AB - This paper examines the effects of the new 65 mile-per-hour (mph) speed limit on U.S. rural highway fatality counts. Separate analyses are conducted for each of the 40 states that had adopted the new (higher) limit by mid-1988. Using monthly Fatal Accident Reporting System (FARS) data from January 1976 through November 1988, time-series regression equations--including policy variables, seasonal variables, and surrogate exposure variables--are estimated for each state. The results suggest that the new laws have increased fatalities on both rural interstate and rural noninterstate highways in most states, but also that these effects differ substantially across the states. For rural interstate fatalities the estimates suggest a median (among the 40 states) effect of the increased speed limit of roughly 15% more fatalities; the median estimates for rural noninterstates suggest a 5% increase in fatalities due to the increased speed limits. Estimates such as those reported here should be revised as more information becomes available. PMID- 2331290 TI - Differences in reported car weight between fatality and registration data files. AB - Two national-level data sources are commonly used together to estimate and compare fatality rates by car weight. The weight of each car in a fatal crash is available on the automated files of the National Highway Traffic Safety Administration's Fatal Accident Reporting System; weight is derived by interpreting the Vehicle Identification Number of each car using a computer algorithm developed and maintained by R. L. Polk & Co. Counts of cars in use, by weight, are available on R. L. Polk & Co.'s National Vehicle Population Profile files; weights are coded from information in state vehicle registration files. However, it appears that there are systematic differences in car weight coding that complicate the use of these two sources together for calculating fatality rates (fatalities per registered car). Overall, the registration data appear to describe a car (of a particular make, model, and model year) as about one hundred pounds heavier than that car is described in the fatality data. The effect is to bias the comparison of fatalities per registered vehicle against lighter cars. Failure to consider this difference can lead to very misleading results. For example, the uncorrected data produce an estimate that the number of occupant fatalities per registered minicompact car (those under 1,950 pounds) was five times the rate in the largest cars (those weighing at least 3,950 pounds). Correcting for differences in car weight reporting produces estimates that the fatality rate in minicompact cars was twice that in the largest cars. Differences by car weight remain, but they are much less than would be concluded from the biased comparison. PMID- 2331291 TI - Restraint effectiveness, occupant ejection from cars, and fatality reductions. AB - The effectiveness of air cushion restraint systems, or airbags, in preventing fatalities is estimated by assuming that they do not affect ejection probability, and protect only in frontal, or near frontal, crashes with impact-reducing effectiveness equal to that of lap/shoulder belts. In order to compute airbag effectiveness, lap/shoulder belt effectiveness and the fraction of fatalities preventable by eliminating ejection are estimated using Fatal Accident Reporting System (FARS) data. Ejection prevention is found to account for almost half of the effectiveness of lap/shoulder belts (essentially all for lap belts only). Airbag effectiveness is estimated as (18 +/- 4)% in preventing fatalities to drivers and (13 +/- 4)% to right front passengers. Drivers switching from lap/shoulder belt to airbag-only protection increase their fatality risk by 41%. PMID- 2331292 TI - Involvement of older drivers in multivehicle side-impact crashes. AB - Side impacts were studied using three separate analyses. National Accident Sampling System (NASS) and National Crash Severity Study (NCSS) cases were reviewed on multivehicle crashes involving fatal chest and abdominal injury by interior contact. Twenty-five cases were analyzed and showed an unusually high involvement of older occupants. Analyses of the 1975-1986 FARS confirmed an overinvolvement. Sixty-four percent of near-side seated occupants were over 50 years old and 36% over 70 in fatal multivehicle side impacts. In contrast, 26% of victims in single-vehicle frontal crashes were over 50 and 8% over 70 years old. Analysis of the 1982-1986 NASS showed that single-vehicle side impacts are not an important injury risk for older drivers, except on icy or wet roads. In contrast, the risk of injury in multivehicle side impacts increases steadily with age and is a major problem for older drivers. The individual NASS and NCSS cases also showed that 88% of the multivehicle side crashes took place at an intersection and that the driver of the struck vehicle frequently caused the crash by driving error (48%) or traffic violation (16%). The majority of cases occurred in daylight hours, on dry roads, and without alcohol involvement. Changes in visual perception, judgment and attention of the older driver may be factors in their missing a traffic signal or turning in front of traffic under the right-of-way. In addition, a reduced tolerance to impact force probably contributes to the injury. Although an analysis of photographs of the side-impacted vehicle indicated that 44% had side-structure deformation that was similar to that produced in the National Highway Traffic Safety Administration (NHTSA) moving deformable barrier test, only 24%-32% of the cases actually addressed the proposed NHTSA dynamic side-impact test. The results of this analysis bear on the agency's preliminary regulatory impact analysis. PMID- 2331293 TI - The application of learning theory to driving confidence: the effect of age and the impact of random breath testing. AB - Despite the dangers, many drivers continue to take risks when driving. This paper outlines an explanation of this risk-taking behavior and the failure of numerous fear-arousing messages to change the manner in which many people drive. Being an occupant in a car and learning to drive may be seen as analogous to systemic desensitization and flooding procedures, in which fear is extinguished and/or a response inconsistent with fear is learned. Once this procedure is complete the fear response is unlikely to be reinstated by messages pointing out possible dangers on the road, because the situations in which the messages are received are usually inappropriate, and many believe that they are superior drivers and therefore not at risk. News presentation of the huge road toll and multiple fatality crashes may only confirm to many people that they are better than average drivers since so many other people have been killed or seriously injured, and they, the superior drivers, have not. A prediction of this account is that driving confidence will increase with increasing age, through the greater on-road fear-reducing experience and increased exposure to the road toll. This prediction was examined in surveys of 2,963 Australian drivers, conducted as part of the evaluation of random breath testing. Respondents were asked to rate their ability as drivers compared with average, and to rate their ability to drive under the influence of alcohol. The overconfidence observed in Canada, Sweden, New Zealand, and the United States was identified in Australian drivers. The predicted increase in confidence with increasing age was supported up to the age of 40 years, after which confidence changed little. Confidence in ability to drive after consuming alcohol increased steadily with age. Finally, it was predicted that the introduction of random breath testing and the associated media campaign partly about the effects of alcohol (which was successful in reducing the road toll) would decrease confidence in ability to drive under the influence of alcohol. Comparison of survey data before and after the introduction of random breath testing did not support this prediction. PMID- 2331294 TI - Isolation and characterization of hyaluronidases from Streptococcus dysgalactiae, S. zooepidemicus and S. equi. AB - 10 out of 10 cultures each of Streptococcus dysgalactiae and S. zooepidemicus and 6 out of 10 cultures of S. equi tested for hyaluronidase produced this enzyme. Hyaluronidase could be precipitated from the cell-free culture supernatant with ammonium sulphate and purified by chromatography on DEAE-cellulose, isoelectric focussing and preparative polyacrylamide gel electrophoresis. The isoelectric points of the hyaluronidases from S. dysgalactiae and S. equi were near pH 5, of that from S. zooepidemicus near pH 6. The hyaluronidases from S. dysgalactiae, S. zooepidemicus and S. equi had molecular weights of about 55,000 D. Maximal enzyme activities developed between 40 degrees C and 45 degrees C and pH 5.6 and 5.8. The Michaelis constants ranged from 7.5 x 10(-2) to 8.8 x 10(-2) mg/ml. Hyaluronidase activities were stimulated by Ca++, Mg++, Mn++, Co++, K+, and Li+ and inhibited by Zn++ and Cd++. PMID- 2331295 TI - Correlation between growth in antibiotic-medium and hemolytic activity of group C and G streptococci. AB - The effect of a subminimal inhibitory concentration of penicillin on the production of bound and free hemolysins by streptococci was examined using sheep red blood cells. A marked decrease of a group C cell-free and bound activities was observed with penicillin at a concentration of 1/3 of the MIC whereas an increase was observed with those of a group G strain. Potassium ferricyanide and anti-streptolysin O (group A streptococcus) were strongly inhibitory for the free activities of both strains. The cell-bound activities were stimulated by addition of RNA during bacterial growth in control cultures and also in drug-containing media. PMID- 2331296 TI - Botulinic toxin detection by counterimmunoelectrophoresis. AB - A counterimmunoelectrophoretic (CIE) technique was developed to detect botulinic toxin type A, and the method was compared with the mouse bioassay. A 100 LD50 concentration was detected within 2 h. Crossed reactions were observed with antitoxins of types B and F. As regards other Clostridium species, precipitin lines were seen between C. sporogenes and antitoxin type A. Foodstuffs artificially contaminated with C. botulinum type A were assayed by means of CIE and mouse bioassay, without recording interference by substances normally contained in foodstuffs. PMID- 2331297 TI - Comparative study of culture methods to detect Yersinia enterocolitica serogroup O3 on swine tongues. AB - Swine tongues were used as a model for evaluation of culture methods for Y. enterocolitica O3. The following three methods were used: Method A consisting of primary culture on DC, McConkey, CIN and SSD agar with additional long-term cold enrichment in PBS and/or selenite broth. Method B--2 min, treatment of samples with 0.5 per cent KOH solution followed by the same cultivation as above and Method C--"cold shock" i.e. incubation of swabs without any medium at -20 degrees C overnight and then inoculated in selenite broth and/or PBS. Methods B and C were approximately twice as effective as Method A. The percentage of detectability ranged from 70 to 90 per cent. CIN agar yielded 20 of 23 positive results when compared with other solid media. A total of 247 smears from pig tongues yielded 60 positive Y. enterocolitica O3 isolations i.e. 27 per cent on average. PMID- 2331298 TI - Digestive tract microflora liberates low molecular weight peptides with immunotriggering activity. AB - Antibiotic digestive tract decontamination in BALB/c-mice resulted in a significant reduction of peritoneal macrophage function and lymphocyte proliferation. Considerable evidence has accumulated showing that certain species of the indigenous gastrointestinal (GI)-tract microflora, e.g. Bacteroides sp., Clostridium sp., Lactobacillus sp., and Propionibacterium sp., liberate low molecular weight peptides which are able to trigger basic immune responses. Eradication of the GI-tract microflora apparently results in a lack of peptide production correlating to immunosuppression in experimental BALB/c-mice. Substitution of peptides in GI-tract decontaminated mice reconstituted macrophage function as well as proliferation of lymphatic tissue. PMID- 2331299 TI - Immunological reactivity and passive protective activity of monoclonal antibodies against protective antigen (PAg) of Leptospira interrogans serovar lai. AB - Monoclonal antibody (MAb) AG1 against the protective antigen (PAg) was produced and characterized. It had been extracted from Leptospira interrogans serovar lai by the chloroform-methanol-water method and was of glycolipid nature (23-30Kd). The fact that the PAg was a serogroup-specific antigen was shown by MAb AG1, because MAb AG1 agglutinated serovars of serogroup Icterohaemorrhagiae. Purified MAb LW2 and LW3 which are agglutinating antibodies of serovar lai and AG1 passively protected hamsters from leptospiral infection. Induction of the reactive oxygen intermediates by MAbs from peritoneal exudate macrophages of mice were observed in the chemical luminescence assay and the MAbs reacted with the PAg in the dot enzyme-linked immunosorbent assay. However, MAb LW4a against the genus-specific antigen present in the sub-surface of leptospiral cells did not show protective and reactive-oxygen-inducing activities; they reacted with the non-protective glycolipid antigen of low molecular weight (Fr I, 10-15Kd) in the dot enzyme-linked immunosorbent assay. These results indicated that anti-PAg antibody exhibited opsonic activity against Leptospira and the production of reactive oxygens by macrophages led to leptospiricidal action as one of the defence mechanisms of the host against leptospiral infection. However, the antibody against the genus-specific glycolipid antigen may not be important for protection against leptospiral infection. PMID- 2331300 TI - Time trends of HIV-I antibody prevalence in homosexual men. AB - 1840 homosexual and bisexual men were tested for human immunodeficiency virus type I (HIV) infection at the Landesinstitut fur Tropenmedizin, Berlin between April 1983 and December 1987. A total of 25.1% were seropositive for HIV, but the percentage was seemingly declining. During the study period we observed also a steady decrease in the prevalence of lymphadenopathy syndrome (LAS), antibodies to hepatitis B and syphilis, and high-risk sexual behaviour in the study population. By adjusting for these changes of population characteristics we assessed the odds of HIV infection which had more than doubled between 1983 and 1986 (prevalence odds ratio 2.43, 95% confidence interval 1.58 to 3.76). In 1987 the HIV prevalence odds showed a drop which, however, was not significant (p = 0.34) when compared with the odds in 1986. Methodological aspects of time trend estimation based on data of voluntary HIV testing are discussed. PMID- 2331301 TI - Abstracts of papers presented at the 42nd meeting of the Deutsche Gesellschaft fur Hygiene und Mikrobiologie. Hannover, October 4-6, 1989. PMID- 2331302 TI - Thymic reticulum of autoimmune mice. II: Ultrastructural studies of mice with lupus-like syndrome (NZB, BXSB, MRL/l). AB - We examined the thymic reticulum of three strains of mice showing symptoms of lupus-like disease. Ultrastructural pathology revealed several features common to the three mouse strains in varying degrees according to sex and age of the mice. Main anomalies included vacuolized aspect of the thymic epithelium, an increased number of macrophages, interdigitating cells and cystic cavities, the presence of a great number of plasmocytes and mastocytes and extensive interstitial fibrosis and arteriosclerosis. The most intriguing finding was the presence of crystal like inclusions in epithelial cells. Some thymuses also showed premature histologic modifications similar to those observed in the ageing involuted thymus. Dysfunction of the epithelial cell secretory system, accumulation of denatured thymic hormone as well as premature organ ageing associated with a loss of thymic function could contribute significantly to the autoimmune phenomenon observed in lupus mice. PMID- 2331303 TI - Abstracts of the Ninth International Workshop on the Immunology of Diabetes. Melbourne, Australia, November 1988. PMID- 2331304 TI - Effects of intramuscular injections of folic acid on serum folates, haematological status and growth performance of growing-finishing pigs. AB - In a first trial, 48 piglets aged 5 weeks, grouped into 6 blocks of 8 pigs each, were used to determine the effect of intramuscular injections of folic acid on serum folates, haematological status, growth performance and carcass characteristics. Each block consisted of 2 pens of 4 pigs; in one pen, pigs received, by weekly intramuscular injections, an increasing volume of a solution containing 5 mg/ml folic acid, while in the other the animals were non-injected controls. The concentration of serum folates in treated pigs was 19% higher (P = 0.005) than in controls. There was no effect of treatment (P greater than or equal to 0.29) on haemoglobin and haematocrit. During the starting period, (5-11 weeks) average daily gain was not influenced by folic acid injections but feed intake and feed conversion were decreased (P = 0.07 and P = 0.05 respectively). No effect of folic acid (P greater than or equal to 0.23) was noted from 11-23 weeks of age, suggesting that the supplement was suboptimal during the growing finishing period. In a second trial, 72 piglets aged 9 weeks were assigned to 6 blocks of 12 animals each. The following treatments were randomly distributed in each block according to a 2 x 3 factorial design: level of feeding (restricted vs ad libitum) and weekly intramuscular injections of increasing volume of solutions containing either 0, 15 or 30 mg/ml of folic acid. The variables studied were the same as in Trial 1. Concentrations of serum folates varied quadratically (P = 0.0001) with the dose injected, a plateau being attained with injections of 15 mg/ml. There was no effect of treatment (P = 0.043) on haemoglobin and haematocrit. During the growing period (9-15 weeks), no effect (P greater than or equal to 0.72) of folic acid was noted on growth performance. However, during the finishing period (15-21 weeks), folic acid given at a dose of 30 mg/ml decreased (P = 0.006) feed intake while no effect (P greater than or equal to 0.13) of the vitamin supplementation was noted on average daily gain and feed conversion. In both trials, there was no effect (P greater than or equal to 0.21) of any treatments on carcass characteristics. These results indicate that a supplement of folic acid administered by intramuscular injections was effective in increasing concentration of serum folates of starting or growing-finishing pigs. This supplement may be associated with a decrease in feed intake. PMID- 2331305 TI - Pseudopregnancy-dependent changes in rat ovarian LH/hCG receptors in relation to membrane lipid fluidity. AB - The specific binding of [125I] hCG to ovarian membrane preparations as well as membrane fluidity have been investigated in immature rats during hormonally induced pseudopregnancy. Membrane fluidity was monitored either by fluorescence polarization analysis of 1,6-diphenyl-1,3,5-hexatriene or by electron spin resonance of 16-, 12-, 5-doxyl stearic acid and CAT 16. A significant positive correlation was found between membrane lipid rigidity and the number of LH/hCG receptors. Luteinization of the ovary induced mobility of molecules in the hydrophobic membrane part at about the C16 carbon level. The changes in rigidity of membrane lipid were the apparent result of alterations in the cholesterol to phospholipids ratio. The results suggest that the increased rigidity of membrane lipid during pseudopregnancy may maximally expose ovarian LH/hCG receptors maintained in a cryptic form. PMID- 2331306 TI - In vivo effects of a treatment with antibodies to adipocyte plasma membranes in the rabbit. AB - Antibodies against rabbit adipocyte plasma membranes were injected in 6-week-old rabbits. Controls received normal IgG. Animals were killed 1, 2, 5 or 9 weeks after treatment. Body weight and food intake were reduced significantly until the 7th week for the live weight and the 5th week for the intake. Whatever the anatomical location considered, adipose tissue was markedly reduced: -75% for week 1 and -20% for week 9 respectively for the total adipose mass. Cell volume and enzymatic activities of G3PDH, LPL and LDH were highly decreased during the first 2 weeks after treatment. Simultaneously the plasma levels of triglycerides and plasma free fatty acids were increased. As shown by others in the rat, it is possible to induce a long-term fatness reduction in the rabbit by treatment with antibodies to adipocyte plasma membranes. The cytotoxic effects of antibodies have also been discussed. PMID- 2331307 TI - Effects of freezing-thawing on the spermatozoon nucleus: a comparative chromatin cytophotometric study in the porcine and human species. AB - Freezing-thawing effects on the nuclei of porcine and human spermatozoa were studied by determining native DNA percentage from fluorescence after acridine orange (AO) staining and by analyzing chromatin structure by a quantitative microspectrophotometric study of Feulgen-DNA complexes before and after freezing. The study of boar spermatozoa revealed no alteration in native DNA percentage after freezing. However, native DNA percentage decreased significantly in human spermatozoa. Feulgen-DNA content and sperm nuclear surface area decreased in both species after freezing. These results prompted us to hypothesize an overcondensation of sperm chromatin after freezing-thawing. This overcondensation may be related to the lower conception rates obtained with human and porcine semen after cryostorage via defective decondensation. PMID- 2331308 TI - Critical analysis of the use of 14C-acetate for measuring in vivo rat cholesterol synthesis. AB - The bulk of cholesterol produced by the liver and the gut enters the mobile pool of body cholesterol. This process is called internal secretion in contrast with the fraction of biosynthesized cholesterol directly eliminated in the feces (fecal external secretion). In rats, under various conditions, a linear relationship was found between the rates of internal secretion measured by the isotope equilibrium method (range: 10-60 mg/day) and the sum of sterol radioactivities measured in liver and intestine 70 min after a [14C]-acetate pulse. In fact, a better correlation was found between the radioactivities of liver sterols and the values for internal secretion. In this new relationship, the ordinate at the origin corresponds to a minimal internal secretion of about 10 mg/day, which implies an important extrahepatic cholesterol production, probably from the gut. Indeed, in adult male rats, fed a semi-purified sucrose rich diet, the relative contribution of this organ to the internal secretion was higher than in adult rats fed a commercial diet and higher than in young animals, whatever the circadian period. It can be concluded that some of the discrepancies observed in the literature about the relative participation of the intestine and the liver in the internal secretion of cholesterol are probably due to differences in experimental and nutritional conditions (age and sex of the animals, diet composition, time of the circadian cycle) rather than to the cholesterol precursor used (3H2O or [14C] acetate) to assess the activity of cholesterol synthesis. Indeed, a comparative study of 3H2O and [14C]acetate incorporation into sterols of enterocytes indicated the same crypt-villus radioactive gradient, regardless of the intestinal site studied (duodenum, jejunum or ileum) and thus validated the use of [14C]acetate. Other experiments however, showed evidence of some local differences in the cytosolic dilution of labeled acetyl CoA by the endogenous cholesterol precursor in rats under various conditions (control or cholestyramine-enriched diet, parenteral nutrition). After intravenous infusion of 1,2[13C]acetate, mass fragmentography of free cholesterol isolated from liver and intestine indicated different 13C-labeling patterns of newly synthesized molecules. They indicate that cholesterol is generally synthesized from acetyl CoA with a lower 13C-content in the liver than in the intestine. The local endogenous flow of acetyl CoA used for cholesterol synthesis was about 2-fold higher in the hepatocytes than in the enterocytes. This conclusion was confirmed by the results obtained with several experimental groups exhibiting a large range of both internal secretion of cholesterol and sterol radioactivities in liver and intestine after [14C]acetate injection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2331309 TI - [Suppression by luteectomy of the simultaneous increase in intramammary pressure and blood oxytocin levels induced by the injection of PGF2-alpha in ewes]. AB - Seven lactating Lacaune ewes underwent either a total luteectomy on day 19 of pregnancy (D19) (compensated from that stage by a daily progesterone supplementation of 25 mg to ensure embryonic survival; group 1:4 animals) or a control laparotomy (group 2: 3 animals). Intra-jugular injection of 200 micrograms of a synthetic PGF2 alpha analogue (Dinolytic, Upjohn) caused an increase in the intramammary pressure (IMP) and a concomitant rise in oxytocinaemia only in the presence of a corpus luteum, ie in all ewes of groups 1 and 2 before D19 and only in those of group 2 after that stage. These experiments confirm that the corpus luteum, and not the other ovarian compartments, releases oxytocin when prostaglandin F2 alpha is administered. PMID- 2331310 TI - Turnover of [14C] sucrose HDL and uptake by organs in the normal or genetically hypercholesterolemic (RICO) rat using a constant infusion method. AB - The turnover and tissular uptake of HDL (d 1.095-1.21) have been compared in normocholesterolemic or genetically hypercholesterolemic rats by a constant infusion method of [14C] sucrose labelled HDL for 8 h. The HDL clearance rate was not significantly smaller in the RICO than in the normocholesterolemic animal (320 +/- 22 microliters.h-1 versus 366 +/- 24 microliters.h-1 per 100 g of rat). It was the same case for the fractional catabolic rate, respectively equal to 7.8 and 9.4 +/- 0.6%.h-1. For both strains, liver and skeletal muscle were the main catabolic sites for HDL. The HDL uptake rates in intestine or kidney were 3-4 fold smaller than those in the liver. In the RICO rat, intestine, testis and adrenals showed a lesser HDL uptake capacity (expressed per g of organ) than the normocholesterolemic rat. PMID- 2331311 TI - [Liver diseases in alpha 1 antitrypsin deficiency syndrome in children]. AB - About 15% of children with alpha-1-antitrypsin-deficiency with proteinase inhibitor type ZZ develop hepatopathy, uninfluenceable in its course. These children already show symptoms of severe cholestatic hepatitis in early infancy as became obvious from data of 13 children being patients in the authors care and suffering from hepatic cirrhosis with alpha-1-antitrypsin-deficiency. At present liver transplantation is the only causal possibility of therapy. Even without highly specialized laboratory the non-laboratory assistant will recognize at least the homozygous alpha-1-antitrypsin-deficiency (PI-ZZ). The therapeutic approach must be directed on treating the patients in such a way that liver transplantation will be possible at a favourable moment and under good conditions. Since PI-ZZ family members suffer similar course of hepatopathy, genetic counsel is of special significance. PMID- 2331312 TI - [The HLA and protease inhibitor (Pi) system in erythropoietic (hepatic) protoporphyria. Family studies]. AB - Relations between porphyrias (porphyria cutanea tarda, variegate porphyria) and HLA- or protease inhibitor (Pi-) system were repeatedly found or supposed. Corresponding investigations do not exist for erythropoietic protoporphyria (EP), for which an autosomal dominant mode of inheritance with highly varying expressiveness (additional genes?) is being discussed. Three families with five EP-patients were examined for possible relations between the manifestations of this disease (skin - and liver changes) and the above-mentioned genetic markers. It was remarkable that three of the patients had the HLA A 3, but nobody of the obvious gene-carriers of this disease without clinical manifestations. On the other hand, two ill couples of siblings were genetically different as to HLA A 3. One couple with liver morphological changes each were different as Pi M-carrier and Pi MS-carrier respectively. Thus, relations between the disease and the genetic markers examined could not be proved. PMID- 2331313 TI - [Mucosa protection--an assessable value? An experimental study in rats]. AB - Reduced mucosaprotection is a main factor for development of peptic ulcer disease. The quantity is difficult to estimate. We did it by measuring the acid output as the aggressive factor and we sized the resulting mucosalesions. In the gastric corpus we could not find any change in mucosaprotectionindex after cimetidine, pirenzepine and vagotomy. But in the duodenum protection was increased after pirenzepine and vagotomy. PMID- 2331315 TI - The effect of hypermagnesemia on serum levels of osteocalcin in an animal model. AB - Using a pregnant goat (Capra hircus) model to study the in vivo effects of hypermagnesemia on serum osteocalcin concentration, magnesium sulfate infusion has been shown to increase circulating levels of osteocalcin. At 2 h after the administration of magnesium sulfate, a 98% increase in Mg2+ concentration over the basal level resulted in: a 38% increase in serum osteocalcin concentration over baseline; a 22% decrease in PTH concentration, and no change in total and ionized calcium concentrations. These in vivo data support previous in vitro results demonstrating that Mg2+ is a potent inhibitor of osteocalcin binding to hydroxyapatite. PMID- 2331314 TI - The LD50, excretion and serum and bone levels of F after a high single F and F + Mg dose in rats with findings on cardiac Ca and Mg. AB - The LD50 for fluoride was elevated from less than 60 mg F/kg body weight to 172 mg F/kg when magnesium (as MgCl2), equivalent to 3 times that of F, was administered by gavage 30 min after the F dose. A dose of 30 mg F/kg elevated the mean steady state of F in serum nearly 1.5-fold and in femoral bone nearly 2-fold when administered with or without the subsequent Mg dose and observed 24 h after the electrolyte dosages. Also, in 24-hour urine the mean F excretion was highest in the F and FMg groups. The total F excretion (fecal + urinary) was elevated 8- and 10-fold when fluoride was administered with or without magnesium, as compared to control levels. Magnesium administration with fluoride did not significantly modify the above mean values of the group given fluoride alone. This suggests that interference with the absorption of fluoride was not the primary protective function of magnesium against the acute toxicity of fluoride. Additional experiments, conducted to further clarify the toxic mechanism of fluoride and the protective mechanism of magnesium, resulted in the following findings: An intraperitoneal dose of 20 mg F/kg elevated fluoride concentration in serum in 1 h about 20 times compared to the controls. Magnesium injected simultaneously with fluoride did not modify the effect of fluoride alone. No significant changes were found in the concentrations of K, Mg, Na or Ca of the lung, skeletal muscle, kidney or liver after these injections except for some trend of elevation of Ca in the heart. However, after a dose of 30 mg F/kg i.p., the heart Ca/Mg mole ratio was elevated within 1 h from 0.037 to 0.194, while all of these rats died within 1 h after the injections. When magnesium, equivalent to 3 times the amount of fluoride was injected, this mole ratio was only 0.095, and all rats in this group survived over 1 h. These results suggest that the lethality of fluoride may be dominantly mediated by the elevated Ca (Ca/Mg ratio) in the heart muscle and that this is correctable by Mg. PMID- 2331316 TI - Effects of potassium and calcium on magnesium and lithium handling in the isolated rat kidney. AB - Acute effects of potassium and calcium on renal lithium and magnesium handling were studied in the isolated rat kidney. Fractional and absolute lithium as well as magnesium transport varied with extracellular potassium in the range of 3.0 6.0 mM. The changes in lithium reabsorption, induced by extracellular potassium are linearly related to the variations simultaneously observed in magnesium reabsorption. Independently of extracellular potassium, lithium reabsorption was stimulated by low calcium comparable to magnesium reabsorption. Bumetanide (3.10( 6) M) lowered lithium and magnesium reabsorption. The results favor the concept that lithium can also be reabsorbed in the thick ascending limb of Henle by as much as 17% of the filtered load, under the conditions of the present experiments. PMID- 2331317 TI - Interaction of magnesium and fluoride in the rehardening and acid resistance of surface-softened bovine enamel in vitro. AB - Surface-softened bovine enamel was submitted in vitro to a treatment with calcifying solutions containing calcium and phosphate (Ca/P ratio = 1.67). Variation in treatment was created by the addition to the solutions of magnesium, fluoride or both. Subsequently, the enamel samples were submitted to two successive softening steps. Alterations of the enamel surface due to the different treatments were evaluated with a hardness tester. No significant difference in the rehardening was observed between samples treated with a magnesium- or a fluoride-containing solution. A 2 X 2 factorial analysis of variance showed that both additions had a highly significant main effect on the rehardening. A significant interaction effect was obtained between magnesium and fluoride. Subsequent acid treatments revealed that only fluoride adequately protected the enamel surfaces from further dissolution. The presence of magnesium seemed to weaken the acid-protective action of fluoride in vitro. PMID- 2331318 TI - Symptomatic hypomagnesemia associated with gentamicin therapy. AB - Seven patients (3 females, 4 males) developed symptomatic hypomagnesemia, hypocalcemia, and hypokalemia following gentamicin therapy. The excessive and inappropriate urinary excretion of magnesium and potassium in the presence of subnormal serum concentrations was noted. A significant correlation was found between the total cumulative dose of gentamicin and serum Mg concentration (r = 0.76, p less than 0.05), as well as between the renal wasting of Mg and the total cumulative dose of gentamicin administered (r = 0.89, p less than 0.01). The gentamicin-induced Mg depletion is a very rare but important complication which is most likely to occur when the drug is given to older patients in large doses over extended periods of time. PMID- 2331319 TI - NBRB Workshop on the Neurochemical Bases of Alcohol-Related Behavior. Bethesda, Maryland, August 31-September 1, 1989. Proceedings. PMID- 2331321 TI - Coupling of poly(ethylene glycol) to albumin under very mild conditions by activation with tresyl chloride: characterization of the conjugate by partitioning in aqueous two-phase systems. AB - Poly(ethylene glycol) activated with tresyl chloride has been covalently linked to albumin as a result of a 2-h incubation in 0.05 M sodium phosphate buffer, pH 7.5, containing 0.125 M sodium chloride (0.344 OSM). The coupling of poly(ethylene glycol) to albumin was demonstrated by the increase in the partition coefficient of the protein in poly(ethylene glycol)-dextran aqueous two phase systems. A linear relationship between the log of the partition coefficient of the poly(ethylene glycol)-albumin conjugate and the degree of modification (measured as the amino groups consumed during the coupling step) has been demonstrated. Countercurrent distribution in the two-phase system showed that poly(ethylene glycol)-albumin was heterogeneous with respect to its partitioning behavior, indicating that the albumin was not uniformly modified with poly(ethylene glycol). PMID- 2331320 TI - Ethanol-nicotine interactions in long-sleep and short-sleep mice. AB - The possibility that common genetic factors regulate initial sensitivities to ethanol and nicotine as well as the development of cross-tolerance between these agents was explored using the long-sleep (LS) and short-sleep (SS) mice. The LS mice proved to be more sensitive to an acute challenge with nicotine than were the SS mice. Segregation analysis (F1, F2, backcross) indicated that ethanol sensitivity and nicotine sensitivity segregate together. Acute pretreatment with nicotine did not significantly affect sensitivity to ethanol, but ethanol pretreatment altered nicotine responsiveness. The LS mice develop more tolerance to nicotine and ethanol than do the SS and they also develop more cross tolerance. These genetically determined differences in initial sensitivities, and tolerance and cross-tolerance development are not readily explained by differences in brain nicotinic receptor numbers. PMID- 2331322 TI - Purification and characterization of polygalacturonases produced by the hyphal fungus Aspergillus niger. AB - Five endo-polygalacturonases (poly(1,4-alpha-D-galacturonide) glycanohydrolase, EC 3.2.1.15) and one exo-polygalacturonase (poly(1,4-alpha-D-galacturonide) galacturonohydrolase, EC 3.2.1.67) were isolated from a commercial pectinase preparation derived from Aspergillus niger. All five endo-enzymes could be purified to homogeneity by affinity chromatography on cross-linked alginate, ion exchange chromatography, chromatofocusing, and gel permeation chromatography. The exo-polygalacturonase was only partially purified but free from endo polygalacturonase activity. The two most abundant endo-polygalacturonases (endo-I and endo-II), with molecular masses of 55 and 38 kDa, respectively, are quite different with respect to their isoelectric point, specific activity, mode of action on oligomeric substrates, and amino acid composition. The physicochemical properties of the other three endo-polygalacturonases (endo-IIIA, endo-IIIB, and endo-IV), present in low amounts, are quite similar to those of the endo-I type. The pH optima of all these endo-polygalacturonases are in the range of 4.3-4.9. PMID- 2331323 TI - Interaction of aluminum with zinc and copper and its effects on pituitary testicular axis: a histological study. AB - To elucidate the interactions between aluminum and certain essential trace metals, an experiment was performed on rats fed diets with suboptimal or optimal levels of zinc or copper. Half of each group of animals were fed the same diet but with 1000 ppm aluminum added. Changes were noted after 120 days. Severe testicular damage was seen in rats fed either the low zinc or the low copper diet. The lesions included a wide range of spermatogenic cell degeneration and tubular atrophy. When aluminum was added to the diet, the testicular destruction of Zn-deficient rats was significantly reduced. This indicated that the presence of aluminum in the diet protected the testis against the damage caused by zinc deficiency. Pituitary glands were examined. Hypertrophy of basophiles was more pronounced in rats fed the suboptimal zinc or copper diet. When aluminum was added to their diet, the changes were reversed. The mechanisms by which aluminum protects male gonadal functions against Zn deficiency are discussed. This study is the first to demonstrate the preventive effect of aluminum against testicular damage caused by zinc deficiency. PMID- 2331324 TI - Study on iron nutritional status in adolescence. AB - A study on iron-deficiency anemia (IDA) in adolescence was conducted among 478 teen-age students in Shanghai. The study indicated that the intake of nutrients among the students was generally insufficient. The lack of protein, calcium, Vitamin A, Vitamin B1, and Vitamin B2 was more serious. The morbidities of IDA among male and female students were 15.8 and 32.6%, respectively, higher in the female group (P less than 0.01). The iron-deficiency sufferers among male and female students were 46.8 and 61.8%, respectively, also higher in the female group (P less than 0.01). The causes of IDA were analyzed by the method of stepwise regression. In a study of the effect of IDA on intelligence and physical development in adolescents, we found that there was no significant effect of IDA on intelligence quotient (IQ) and school performance. However, the speed and endurance capabilities of students of both sexes were correlated directly with hemoglobin level. In female students, the speed capability was correlated directly with the serum ferritin content. On the basis of these findings, a special 3-month school lunch program was initiated. The results indicate that a comprehensive, rational, and balanced diet is beneficial to hemoglobin, free erythrocyte porphyrin, and serum ferritin contents and improves adolescent development. PMID- 2331325 TI - The effect of Chinese tea on occurrence of esophageal tumor induced by N nitrosomethylbenzylamine in rats. AB - Five groups of rats (40 rats per group) were given five different varieties of Chinese tea (1 g/50 ml) and another two groups of rats (a positive control and a negative control) were given tap water as drinking water. Except for the negative control group, all the animals were intubated with N-nitrosomethylbenzylamine (NMBzA, 5 mg/kg body wt/week). Half of the animals in each group were sacrificed after 6 weeks and the remaining animals at the end of 12 weeks. The incidences of esophageal mucosa lesions (16-59%) at the end of 6 weeks were significantly lower in the tea-treated rats than in the positive control group (100%). The incidences of esophageal tumor at the end of 12 weeks (42-67%) were also significantly lower in the tea-treated groups than in the positive control group (90%). The same phenomenon was found with respect to the size and number of tumors in each tumor bearing animal. The relative anticarcinogenic effects of the five varieties of Chinese tea were different. The Fujian oolong tea and jasmine tea exhibited the strongest effects. The results suggest that Chinese tea can effectively inhibit the carcinogenesis caused by an N-nitroso compound. PMID- 2331326 TI - Malate and lactate dehydrogenases of a freshwater catfish: impact of endosulfan. AB - A sublethal concentration of technical grade endosulfan (END) inhibited 35 to 55% of the activities of cytoplasmic malate dehydrogenase (cMDH), mitochondrial malate dehydrogenase (mMDH), and lactate dehydrogenase (LDH) in the liver and the skeletal muscle of a freshwater catfish, Clarias batrachus, after 7 days of exposure. The activity remained in the inhibited state up to 28 days. The withdrawal of END from the medium after 1 week of exposure gradually restored the activities to control levels within 21 days in the skeletal muscle and 28 days in the liver. The administration of actinomycin D or cycloheximide between the 14th and the 21st day of the withdrawal of END almost completely inhibited the withdrawal-dependent recovery in the activities of all the three enzymes. This indicates de novo synthesis of the enzymes during the recovery period. A conjoint treatment of END and triiodothyronine (T3) raised the activities of cMDH, mMDH, and LDH in the liver and the skeletal muscle up to the control levels. This shows that the inhibitory effect of END may be relieved in presence of T3. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed few changes in the pattern of cytoplasmic proteins of the liver and the skeletal muscle in response to exposure to END. PMID- 2331327 TI - Toxicity tests of soil contaminated by recycling of scrap plastics. AB - The present investigation studied the toxicity of soil contaminated by untreated discharge from a factory that recycles used plastics. The nearby agricultural areas and freshwater fish ponds were polluted with high concentrations of Cu, Ni, and Mn. Water extracts from the contaminated soil retarded root growth of Brassica chinensis (Chinese white cabbage) and Cynodon dactylon (Bermuda grass) where their seeds were obtained commercially. The contaminated populations of C. dactylon, Panicum repen (panic grass), and Imperata cylindrica (wooly grass) were able to withstand higher concentrations of Cu, Ni, and Mn, especially C. dactylon, when compared with their uncontaminated counterparts. PMID- 2331328 TI - A study on the dose-response relationship between asbestos exposure level and asbestosis among workers in a Chinese chrysotile product factory. AB - The dose-response relationship for asbestos exposure in a chrysotile product factory was studied. The past gravimetric dust concentration values, obtained from different worksites, were converted into fiber concentration values according to conversion factors that were worked out by simultaneous sampling in this study. The conversions were made so that exposure could be expressed in fiber-years (f-yr). Asbestosis was diagnosed on the basis of chest radiographs and occupational histories. Cumulative dust exposure (f-yr) was calculated up to the date of diagnosis for asbestosis patients, and up to September 1982 for the remaining workers. A dose-response relationship expressed as fiber-years exposed vs cumulative prevalence of asbestosis was established by the life table method on the basis of these data. Predicted 3 and 1% prevalence of asbestosis corresponded to 43 and 22 f-yr exposure, respectively. Considering that a worker can work for 35 years, these doses are commensurate with dust concentrations of 1.22 and 0.63 f/ml, respectively. It is recommended that 1 f/ml be taken as the maximum allowable concentration of airborne asbestos dust for the workplace with an anticipated prevalence of about 2% asbestosis after 35 years of exposure. PMID- 2331329 TI - Relieving the pressure. PMID- 2331330 TI - Leading the way. PMID- 2331331 TI - More of Orem--Part 2. PMID- 2331332 TI - Those were the days.... PMID- 2331333 TI - Implications for care. PMID- 2331334 TI - Structure of (R)-tetrahydro-2-furancarboxylic acid monohydrate. AB - C5H10O4, Mr = 134.31, monoclinic, P2(1), a = 11.670 (2), b = 6.177 (3), c = 10.704 (2) A, beta = 115.11 (2) degrees, V = 698.7 (4) A3, Z = 4, Dm = 1.26, Dx = 1.28 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 9.69 cm-1, F(000) = 288, room temperature, R = 0.046 for 1047 reflections with [Fo[ greater than 3 sigma(F). There are two independent molecules of the title compound in the crystal. No twofold symmetry is observed in the tetrahydrofuran rings. Hydrogen bonds between water molecules and carboxylic acid groups stabilize the crystal structure. PMID- 2331335 TI - Structures of three N-pyridyl-2-phenylsuccinimides and structural evidence for substituent effects on anticonvulsant properties. AB - T = 295 K, Mo K alpha with lambda = 0.70930 A. Compound (I-6): C15H12N2O2, Mr = 252.26, monoclinic, P2(1)/c, a = 8.441 (3), b = 15.269 (1), c = 9.745 (2) A, beta = 92.34 (2) degrees, V = 1254.9 (19) A3, Z = 4, Dx = 1.335 g cm-3, mu = 0.85 cm 1, F(000) = 528, R = 0.0345 for 1682 observed reflections. Compound (I-10): C16H14N2O2, Mr = 266.30, monoclinic, P2(1)/n, a = 11.637 (1), b = 5.793 (1), c = 20.778 (2) A, beta = 105.26 (1) degrees, V = 1351.3 (25) A3, Z = 4, Dx = 1.309 g cm-3, mu = 0.82 cm-1, F(000) = 560, R = 0.0379 for 1840 observed reflections. Compound (I-11): C16H13C1N2O2, Mr = 300.74, triclinic, P1, a = 9.076 (3), b = 9.366 (1), c = 10.477 (3) A, alpha = 118.27 (2), beta = 93.85 (2), gamma = 105.26 (1) degree, V = 737.2 (15) A3, Z = 2, Dx = 1.350 g cm-3, mu = 2.61 cm-1, F(000) = 312, R = 0.0528 for 2018 observed reflections. The three N-pyridyl-2 phenylsuccinimides [N-(3-methyl-2-pyridyl)-2-p-chlorophenylsuccinimide (I-11); N (3-methyl-2-pyridyl)-2-phenylsuccinimide (I-10) and N-(3-pyridyl)-2 phenylsuccinimide (I-6)], examined by means of X-ray structure analysis, have been previously subjected to extensive pharmacological screening, with regard to their anticonvulsive activity. Pharmacological properties of the compounds examined are clearly connected with the conformation of the molecules. The conformation of the molecules of biologically active derivatives (I-10) and (I 11) differs from the conformation of the inactive molecule of (I-6). This difference involves relative positioning of the pyridyl ring and the succinimide moiety. The Cl atom in (I-11) has only a minor effect on the conformation and geometry of the molecule in comparison with (I-10). PMID- 2331336 TI - Structure of N,N,N',N'-tetrakis(2-fluoro-2,2-dinitroethyl)oxamide by the consistent electron density approach. AB - C10H8F4N10O18, Mr = 632.22, monoclinic, Pc, a = 7.8885 (6), b = 6.7787 (4), c = 21.595 (2) A, beta = 108.21 (1) degree, V = 1096 (1) A3, Z = 2, Dx = 1.914 g cm 3, lambda(Cu K alpha) = 1.5418 A, mu = 18.7 cm-1, F(000) = 636, T = 293 K, 1791 unique data, 1733 with I greater than 3 sigma (I), R = 0.047. The structure was solved by the consistent electron density approach (CEDA), in which a small starting set of random phases was refined and expanded by the application of restraints to the electron density. A refinable preliminary structure was obtained by fitting a model to a 3 A map, calculated with 27 reflections (all data with d greater than 3 A, and magnitude of Fo greater than 170) whose phases had been determined by the CEDA. The molecule has an extended, open conformation; the two pairs of fluorodinitroethyl substituents located across the molecular center from each other show i and C2 pseudo-symmetry respectively. PMID- 2331337 TI - Structure of 5-hydroxy-5-phenyl-7-azatricyclo[7.4.0.02,7]trideca-2,9(1), 10,12 tetraen-8-one by the consistent electron density approach. AB - C18H15NO2, Mr = 277.3, monoclinic, P21/n, a = 7.408 (2), b = 22.311 (7), c = 8.613 (2) A, beta = 103.53 (3) degrees, V = 1384 (1) A3, Z = 4, Dx = 1.33 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.94 cm-1, F(000) = 594, T = 293 K, 2229 unique diffractometer data, 963 with I greater than 3 sigma(I), R = 0.050. Structure solution was by the consistent electron density approach which combines the concepts of the OMIT map and density modification procedures. The benzolactam portion of the molecule is highly planar; most bond lengths and angles have typical values. PMID- 2331338 TI - Statistical conclusion validity of rehabilitation research. A quantitative analysis. AB - The findings of 100 data-based studies exploring the effectiveness of rehabilitation procedures were reviewed and analyzed. The statistical conclusion validity was determined by computing post hoc power coefficients for the statistical hypotheses tests included in the review studies. The data analysis revealed that the median power to detect a small effect size in the studiesreviewed was 0.08. The median power to detect medium and large effect sizes was 0.26 and 0.56, respectively. The results suggest the possibility of a high rate of type II experimental errors in the rehabilitation research. A type II error represents a false-negative conclusion and occurs when a researcher supports a null hypothesis that was false and should have been rejected. PMID- 2331339 TI - Functional medicine. PMID- 2331340 TI - Wheelchair-mounted robot manipulators. Long term use by patients with Duchenne muscular dystrophy. AB - This report relays practical clinical information about the modification and use of commercially available training robot manipulators. Such manipulators were used to increase independence in the activities of daily living of patients with advanced Duchenne muscular dystrophy. The control panels of five industrial robot manipulator training devices were modified for use by advanced Duchenne muscular dystrophy patients. Six patients with only residual finger movement, three of whom were dependent on respiratory support, mastered the use of these devices. The four patients with long-term access employed their manipulators for facilitation of activities of daily living an average of 8 h a day for 3 +/- 1.8 yr. There was approximately 3 h of estimated attendant care time saved per patient per day. PMID- 2331341 TI - Electrical activity and soreness in muscles after exercise. AB - Electrical activity and soreness in the quadriceps muscles were examined during a 48-h period after eccentric (EC) and concentric contraction (CC) to study the amplitude and frequency characteristics of the electrical signal after exercise and to study the relationship between the electrical signal and muscle soreness. The exercise protocol included a step test performed for 15 min using a 46-cm step in which one quadriceps contracted eccentrically and one contracted concentrically. Electrical activity was quantified by computing both root mean square electromyograph (rmsEMG) and mean power frequency of the myoelectrical signal during low-level contractions of the muscles. Recordings of muscle activity were made before exercise, immediately after exercise, 1, 12, 24 and 48 h after exercise in 12 volunteer subjects (mean age 28.5 yr). Recordings were made with the subject seated, holding the leg being tested slightly off the ground. Subjects were given a subjective pain rating scale. The before exercise values for rmsEMG (EC = 13.3 microV; CC = 13 microV) and mean power frequency (EC = 55.3 Hz; CC = 54.4 Hz) were within the range that would be expected for surface electrodes. The mean rating of soreness for the eccentrically exercised muscles ranged from slightly uncomfortable at 12 h after exercise to sore during the period 24-48 h after exercise. Subjects reported the concentrically exercised muscles as normal to slightly uncomfortable during the whole recording period. Analysis of variance revealed a significant (P less than 0.05) difference between EC and CC rmsEMG value at 1 h after exercise (EC = 17.2 +/- 7.6; CC = 12.3 +/- 5.5) and at 12 h after exercise (EC = 15.0 +/- 5.0; CC = 12.3 +/- 4.2). The results suggest that an increase in the electrical activity of muscles is needed to produce the same pre-exercise contraction after performing eccentric exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331342 TI - Common deficiencies of NIDRR research applications. AB - The purpose of this article was to identify and describe those deficiencies determined by nonfederal peer reviewers during the most recent 1989 NIDRR research competition to mitigate successful funding support from the lead federal agency concerned with medical rehabilitation research. In 1989, 232 field investigator-initiated research applications were received in response to the Federal Register announcement of September 8, 1988. Of these, 57 or 24.5% were assigned to the Medical Sciences Programs office. Six applications were ultimately approved and funded (10.7%). The remaining 51 (89.5%) were statistically analyzed to determine deficiencies significant in warranting disapproval. The 51 applications averaged 5.68 deficiencies each. Five types of research error accounted for 76.8% of all deficiencies noted by reviewers. These included methodologic errors (25) and inadequate control of subject variables (25), followed by inappropriate research design (24), poor conceptualization of problem/approach (21) and incorrect statistical analysis (14). The top ranked singular deficiency was poor conceptualization of problems or approach. Other flaws warranting lowering of potential scores by reviewers included excessive budget requests, duplication of effort with on-going supported research, inadequate background of investigator and weak dissemination and utilization plans. In conclusion, many applications are submitted for the NIDRR field investigator-initiated research program competitions that are significantly deficient. Those identified areas of deficiency cover most oF the conceptualization, research design and methodologic criteria essential for valid, creditable scientific investigation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331343 TI - Spinal nerve stimulation in S1 radiculopathy. AB - The H reflex plays an important role in electrodiagnosis, but it does not give specific information about any particular segment of its long conduction pathway. Direct stimulation at the S1 spinal nerve might provide more complete information by dividing the H reflex pathway into its peripheral and spinal conduction portions. Patients with electromyographic evidence of S1 radiculopathy (n = 77) and normal control subjects (n = 56) were evaluated. Standard H reflex conduction studies were followed by monopolar needle stimulation of the first sacral spinal nerve. The ratio of the spinal nerve latency to the H reflex latency (S1 ratio) was calculated. The abnormal S1 ratio seen in 77% of the subjects suggested relative slowing within the spinal segment of the nerve. The remainder of the subjects with S1 radiculopathy had slowed conduction also affecting the peripheral segment that could have been caused by Wallerian degeneration. The S1 ratio can provide evidence that H reflex conduction slowing is the result of injury involving the intraspinal nerves. This technique should be especially useful in cases of acute lumbosacral injury when needle electromyographic study is often nondiagnostic. PMID- 2331344 TI - Starting out. The first six months posthospital for spinal cord-injured veterans. AB - Thirty-one former patients were contacted 6 mo after their completion of a spinal cord injury rehabilitation program: 14, paraplegics; 8, complete quadriplegics; 9, incomplete quadriplegics. Mean age was 38.5 yr. Most respondents were living in a family setting. Income ranged from substantial to barely adequate. Half of the respondents needed no assistance with activities of daily living; for the others, family members were the primary helpers. Almost all described their social contacts as sufficient for their needs. Half had not needed to use community resources for the disabled; the others had used a range of resources. Two respondents were employed, four were in school, six others had plans for eventual employment. Neither extent of disability nor income seemed related to likelihood of entering the workforce. Most respondents reported frequent local travel; some had traveled extensively. The large majority engaged in one or more hobbies and/or physical activities. Just over half of the respondents had had no sexual activity after discharge. Of the sexually active, half had found the experience frustrating. Except for the 30- to 39-yr-old respondents, the majority expressed satisfaction with most aspects of their lives. PMID- 2331345 TI - Voluntary control of submaximal grip strength. AB - Stokes (J Occup Med; 1983;25:683-684) proposed that feigned weak hand grip can be distinguished from sincere efforts by examining force measurements for the different handle positions of the Jamar hand dynamometer. Sincere efforts yield a curvilinear relationship between grip force and handle position; feigned efforts yield a horizontal, linear relationship. The purpose of the present set of three experiments was to investigate the degree of control normal subjects have over submaximal effort and their ability to feign weakened grip. In Experiment 1 we found that subjects instructed to exert a specific amount of submaximal effort (50%) did not produce a response pattern of grip force consistent with Stokes' hypothesis. In Experiment 2 we found a linear relationship between the degree of submaximal effort and grip force for efforts of 30, 50, 70, and 90% of maximal effort. In Experiment 3 we found that subjects, with proper instruction as to the amount of effort to exert, can produce feigned submaximal efforts similar to the sincere, maximal efforts of injured people. Simple maximal grip force measurements are insensitive to the different motor strategies used in maximal and submaximal efforts and may provide little evidence for the detection of feigning. PMID- 2331346 TI - Ischemia in the dorsal hippocampus is associated with acute extracellular release of dopamine and norepinephrine. AB - The cerebral dialysis technique was employed to monitor extracellular concentrations of dopamine (DA), norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the dorsal hippocampus of gerbils before and after cerebral ischemia induced by carotid artery occlusion. Extracellular concentrations of DA and NE in the dorsal hippocampus increased from baseline levels of less than 35 fmol/collection interval to 180 and 200 fmol/collection, respectively, within 36 minutes following carotid artery ligation (n = 8 animals). Extracellular concentrations of the DA metabolites, DOPAC and HVA, did not change significantly following carotid artery ligation. These data demonstrate that ischemia in the dorsal hippocampus is associated with a mared release of DA and NE. This release may contribute to the selective vulnerability of the dorsal hippocampus to neuronal damage during ischemia. PMID- 2331347 TI - Glycoprotein synthesis in the subcommissural organ of the chick embryo. II. An immunochemical study. AB - In the chick embryo, A74 immunoaffinity chromatography allowed to purify specific glycoproteins relevant to the SCO ventricular secretory process. The eluted fractions of the subcommissural organ (SCO), the cerebral hemispheres (CH) and the medulla oblongata (MO) were compared using the Concanavalin A (Con A) and wheat germ agglutinin (WGA) staining procedures after western-blotting. Analysis of the optical density of the reactive bands allowed to estimate the relative concentration of the various glycopeptides in the eluted fractions. In the SCO eluted fractions at least ten Con A-positive glycopeptides were identified, their apparent molecular weight ranging from 240 to 42 kD. Only three of these appeared to be WGA-positive (98, 88, and 52 kD). In the CH-eluted fractions only a 52 kD Con A- and WGA-positive glycopeptide was revealed, while in the MO-eluted fractions a 32 kD glycopeptide was also Con A- and WGA-positive. These results are discussed in regard to the known biosynthesis pathway of complex type glycoproteins. PMID- 2331348 TI - Developmental change of dopamine beta-hydroxylase activity in cerebrospinal fluid of epileptic and non-epileptic children. AB - The developmental change of dopamine beta-hydroxylase (DBH) activity in cerebrospinal fluid (CSF) of epileptic children was studied. Non-epileptic children showed lower DBH activity in CSF than adult, and its activity increased with age. In contrast, epileptic children showed no increase in DBH activity with age. DBH in CSF may be a good index of noradrenergic function in child brain. The results on developmental change in DBH in CSF suggest that refractory epilepsy with long term medication has decreased activity in central noradrenergic neurons. PMID- 2331349 TI - A new approach to immunoFET operation. AB - A new method is presented for the detection of an immunological reaction taking place in a membrane, which covers the gate area of an ISFET. By stepwise changing the electrolyte concentration of the sample solution, a transient diffusion of ions through the membrane-protein layer occurs, resulting in a transient membrane potential, which is measured by the ISFET. The diffusion rate is determined by the immobile charge density in the amphoteric protein layer, which changes upon formation of antibody-antigen complexes. No membrane potential is induced at zero fixed charge density as occurs at a protein characteristic pH. Isoelectric points of embedded proteins can be determined by detecting the zero potential response. Up to now, the authors have studied the membrane adsorption of lysozyme, human serum albumin (HSA) and the immune reaction of HSA with the antibody anti-human serum albumin (alpha HSA). The influence of protein parameters on the amplitude of the transient can be described with an empirical equation. Assuming Langmuir behaviour, the protein concentration in the solution can well be correlated with the concentration in the membrane. This new detection method is unique concerning direct measurements of charge densities and isoelectric points of amphoteric macromolecules adsorbed in the membrane. The simple procedure of one incubation stage followed by one detection stage, without separate washing and labelling techniques, gives direct information about specific charge properties of the macromolecules to be studied. PMID- 2331350 TI - A fast responding fibre optic glucose biosensor based on an oxygen optrode. AB - A fast responding glucose biosensor for the continuous determination of glucose is presented. The biosensor is based on an oxygen optrode, which measures the consumption of oxygen via dynamic quenching of the fluorescence of an indicator by molecular oxygen. Glucose oxidase (GOD) is immobilised onto the surface of this oxygen optrode by adsorption to carbon black and by crosslinking with glutardialdehyde. Carbon black is used as an optical isolation to protect the optrode from the interference of ambient light and sample fluorescence. The measurements were performed in a flow through cell with air saturated glucose standard solutions (phosphate buffered saline pH 6.9). The effect of four different qualities of GOD in relation to response times (the time required to reach 90% of the steady-state signal, tau 90, was 8-60 s, the linear analytical range (0.01 to 2 mM glucose) and the long-term stability (tau 1/2 was 1-20 weeks) were investigated. A simple device is presented capable of enlarging the analytical range up to 200 mM glucose concentration. PMID- 2331351 TI - Enzyme entrapped polypyrrole modified electrode for flow-injection determination of glucose. AB - Immobilization of glucose oxidase in electropolymerized polypyrrole film on the surface of a platinum wire electrode, provides a convenient sensor for flow injection glucose determination. An upper limit of linear response for 100 microliters injected sample volume was estimated as 20 mM, whereas a 500 microliters injected sample volume gave an estimated detection limit of 0.5 mM. A simple electrode preparation procedure allows quick electrode renewal before each series of measurements. PMID- 2331352 TI - Molecular genetics of hypercholesterolemia. PMID- 2331353 TI - Tetanus in Finland: diagnostic problems and complications. AB - In a 16-year nationwide study in Finland 106 patients were diagnosed as having tetanus. Tetanus was diagnosed on the first visit to a doctor in half the patients, it was suspected in 28% but not considered in 22%. Diagnosis of tetanus may be delayed if a patient is elderly or has no known primary lesion. Abnormal EEGs and CSF findings with increased protein level were unexpectedly common (76% and 24% respectively). The most significant complications were cardiac arrhythmias (34%), blood pressure lability (32%), an increased haemorrhagic tendency (28%), an increase in thrombosis (8%) and/or of anoxic periods (16%) and death (11%). Intensive care has markedly improved the prognosis of tetanus; the main problems at present are difficulty of early diagnosis and treatment of complications of the most serious cases. PMID- 2331354 TI - Predictors of functional capacity in elderly Finnish men; a path analysis. AB - Factors predicting functional capacity in 1984 in men aged 65-84 years were studied by path analysis in 716 men from eastern and southwestern Finland as part of the 25 year follow up of the East-West Study i.e., the Finnish part of the Seven Countries Study. The variables selected to predict functional capacity were measured in 1959, 1964, 1969, 1974 and 1984. Diastolic blood pressure levels explained more of the variation in future functional capacity than did those of systolic blood pressure. Body mass index explained more of the variation in the future functional capacity in the east than in the south west. Serum cholesterol concentration and smoking habits were not associated with future functional capacity, accounting for only up to 10.7% and 4% of the variation in functional capacity in old age in the east and the south west respectively. There are area differences between the predictors of functional capacity, but a single health or health practice variable plays little part in the variation in functional capacity. PMID- 2331355 TI - New views into the pathogenesis of reactive arthritis. PMID- 2331356 TI - Sialomucin at the resection margins and likelihood of local recurrence of carcinoma of the rectum after anterior resection. AB - The histochemical changes in mucin at the postoperative resection margins in carcinoma of the upper and middle third of the rectum after anterior resection were studied retrospectively in 52 patients. The sialomucinous change was most likely to occur at the intestinal margins of those patients who had tumour recurrence (P less than 0.001). The histological types of tumour, degree of differentiation, Dukes' stages and their distance from the anal verge were virtually the same in patients with and without tumour recurrence. By using high iron diamine-alcian blue staining technique we identified patients with higher risk conditions of tumour recurrence after anterior resection. This technique should increase the likelihood of a cure for patients with recurrent carcinoma of the rectum after anterior resection. PMID- 2331357 TI - The role of intestinal microflora in preserving intestinal integrity and health with special reference to lactic acid bacteria. PMID- 2331358 TI - Small vessel disease (SVD) in patients with unexplained ventricular arrhythmia and dilated congestive cardiomyopathy. AB - Small vessel coronary disease is not commonly found in endomyocardial biopsies (EMB) of nondiabetic patients with clinical evidence of ischemic heart disease, congestive heart failure, or ventricular arrhythmia (VA). In 166 patients studied by heart catheterization and multiple right ventricle EMB, we identified 4 patients with histologic evidence of small vessel disease and normal coronary arteriograms. Two patients were suffering from VA without an obvious cardiac cause. Of the other two, one initially showed frequent ventricular tachycardia attacks followed by congestive heart failure alone. In both patients, the cardiac chambers were dilated and the left ventricular function seriously impaired. In all four patients, the histologic examination of right EMB revealed a wall thickening of the precapillary arterioles and capillary vessels. At ultrastructural examination, an increased thickening (four or five times normal) of the subendothelial lamina and of the basement membrane of capillary pericytes was found. Degenerative changes of cardiac myocells were found in all cases. PMID- 2331359 TI - The significance of eosinophils in mild and moderate acute cardiac allograft rejection. AB - The presence of eosinophils has previously been associated with severe acute cardiac allograft rejection. This appears to be a relatively uncommon finding, judging from our experience and the paucity of information appearing in literature. We report three cases where a prominent infiltrate of eosinophils was noted on endomyocardial biopsy following cardiac transplantation. There was no evidence of severe acute rejection in any of these three patients, and one patient had only mild acute rejection without even focal myocardial necrosis. An infiltrate, which includes eosinophils, does not appear to be restricted to severe acute cardiac allograft rejection. Therefore, when eosinophils are noted in endomyocardial biopsy specimens, decisions to revise the immunosuppressive regimen of cardiac transplant recipients should continue to be based upon established conventional histologic criteria. PMID- 2331360 TI - Computer-based reconstructions of the cardiac ventricles of human embryos. AB - The early appearance and relatively large size of the embryonic heart suggest that cardiac function is critical to early development. Previous studies had shown that an index derived from curvature and thickness of the ventricular wall provides an estimate of the pressure generating capacity of the myocardium. To obtain an estimate of the functional capability of the embryonic ventricle, images of serial histologic sections of eight normal human embryos, ranging from stages 9-23, from the Carnegie Embryological Collection were chosen for study. The contours of ventricular components were digitized and entered into a computer, and three-dimensional (3-D) reconstructions were created. Volumes of the components of the ventricles were determined, including the compact or outer portion of the ventricular wall, the cardiac jelly, the overall volume containing trabeculated myocardium in each ventricle, and the proportion of that volume consisting of muscle. The results showed a highly significant increase in overall ventricular size as a function of Carnegie stage and crown-rump length. Cardiac jelly was prominent in the early stages but was progressively replaced by the trabeculated muscle. The volume containing trabeculae had a consistent proportion of muscle, averaging 65%, for all stages after its appearance in stage 13. Curvature and thickness measurements of the compact part of the ventricles were made from images of the reconstructions. The mean curvature-thickness index (CTI) for the embryo hearts ranged from 0.24-0.61, and there was a significant increase in the index as a function of stage and crown-rump length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331361 TI - Histopathological assessment of endomyocardial biopsy in children: I. Semiquantitative study on the hypertrophy of cardiac myocytes. AB - Over 200 endomyocardial biopsies in pediatric patients have been performed since 1962, and an appropriate interpretation of myocardial hypertrophy in biopsy specimens at different ages is now necessary. The diameter of myocytes was measured in 108 biopsy specimens and 209 autopsy specimens from pediatric cases. There was a gradual increase in the myocyte diameter according to age in the biopsy and autopsy specimens. The diameter became adult size at 13 to 15 years of age in the right ventricle and at 9 to 15 years in the left ventricle. The myocyte size of diseased hearts was greater than that of normal hearts at each age. The coefficient of variance of the mean myocyte diameter in heart muscle disease, including hypertrophic cardiomyopathy and dilated cardiomyopathy, was greater than in other hearts. These results suggested that it is possible to ascertain myocardial hypertrophy by measuring the diameter of cardiac myocytes. A proposed grading system of the degree of myocyte hypertrophy for the biopsy specimens at various pediatric ages is reported. PMID- 2331362 TI - Reperfusion injury in ischemic myocardium: effects of nifedipine and verapamil. AB - Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Calcium entry into myocytes has been implicated in this effect, and calcium channel-blocking agents have been used in attempts to prevent or limit such damage. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either nifedipine or verapamil (both clinically employed calcium channel-blocking agents) prior to and during coronary reperfusion. During reperfusion, nifedipine produced a lowering of mean arterial pressure, while mean arterial pressure was constant in verapamil-treated pigs and rose in pigs not receiving drugs. Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were independently graded on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for nifedipine-treated animals than for controls. Ischemic damage in verapamil-treated pigs was not different from that seen in control animals, except for a slight improvement in myofibrillar appearance. We conclude that nifedipine, administered prior to and during reperfusion of myocardium, protects against reperfusion injury. The mechanism of this protective effect may be attributable, in part, to afterload reduction and, in part, to inhibition of transmembrane calcium flux in cardiac fibers. PMID- 2331363 TI - The effect of perfluorochemical fluosol-DA (20%) on myocardial infarct healing in the rabbit. AB - Although the perfluorochemical Fluosol-DA 20% has been shown to reduce myocardial infarct size, its effect on the evolution of infarct healing has not been determined. Rabbits (n = 91) were randomized to ether-oxygenated Fluosol-DA (20 ml/kg) administered intravenously at the time of reperfusion after 30 min of coronary occlusion or no intervention. Animals were sacrificed at 1, 3, 7, and 14 days after infarction. Infarct size was significantly reduced in Fluosol-DA treated animals when compared with controls at one and three days. Infarct thinning was observed at one and three days in both groups. Left ventricular wall thickness in the infarcted area was greater with Fluosol-DA than control at 7 and 14 days. Increasing amounts of foamy macrophages containing perfluorochemical particles were noted in treated animals at 7 and 14 days. No differences were noted in hydroxyproline content between groups. These studies suggest that Fluosol-DA results in persistence of foamy macrophages without significantly altering infarct topography in the temporary occlusion rabbit model. PMID- 2331364 TI - Occlusion of aortocoronary vein grafts in association with bovine pericardium. AB - A case is reported in which the use of heterologous bovine pericardium in coronary revascularization was associated with firm adhesions and complete occlusion of all vein grafts after eight months. Heterologous pericardial substitutes may have a deleterious effect on vein grafts and may not avert epicardial-pericardial adhesions. PMID- 2331365 TI - Quadricuspid aortic valve. AB - A rare case of a quadricuspid aortic valve discovered incidentally at autopsy is described. A shallow raphe joined the supernumerary and adjacent cusp, possibly representing early fusion of the commissures. There was no symptomatic hemodynamic abnormality. Other than a probe-patent foramen ovale, no congenital anomalies were present. This is only the sixth example of a quadricuspid aortic valve with a raphe reported in the English language literature. PMID- 2331366 TI - Rapid purification of PCR products for DNA sequencing using Sepharose CL-6B spin columns. PMID- 2331367 TI - A procedure for productive coupling of synthetic oligonucleotides to polystyrene microtiter wells for hybridization capture. PMID- 2331368 TI - A simple water level detection device. PMID- 2331369 TI - Automatic karyotyping of plant chromosomes by imaging techniques. AB - Chromosomes of Crepis capillaris (L.) Wallr. were analyzed using a newly developed chromosome image analyzing system, CHIAS-mini. The CHIAS-mini is a desktop system which consists of an ordinary 16-bit personal computer and an image processor as the main frames. Data acquisition, karyotyping and idiogramming of the plant chromosomes were automatically carried out with some manual interaction. The data obtained were comparable to those obtained manually and by a standard image analyzer already developed. PMID- 2331370 TI - Real-time multi-wavelength fluorescence imaging of living cells. AB - We describe a new real-time fluorescence video microscope design for capturing intensified images of cells containing dual wavelength "ratio" dyes or multiple dyes. The microscope will perform real-time capture of two separate fluorescence emission images simultaneously, improving the time resolution of spatial distribution of fluorescence to video frame rates (30 frames/s or faster). Each emission wavelength is imaged simultaneously by one of two cameras, then digitized, background corrected and appropriately combined at standard video frame rates to be stored at high resolution on tape or digital video disk for further off-line analysis. Use of low noise, high sensitivity image intensifiers, coupled to CCD cameras produce stable, high contrast images using ultra low light levels with little persistence or bloom. The design has no moving parts in its optical train, which overcomes a number of technical difficulties encountered in the present filter wheel designs for multiple imaging. Coupled to compatible image processing software utilizing PC-AT computers, the new design can be built for a significantly lower cost than many presently available commercial machines. The system is ideal for ratio imaging applications; the software can calculate the ratio of fluorescence intensities pixel by pixel and provide the information to generate false-color images of the intensity data as well as other calculations based on the two images. Thus, it provides a powerful, inexpensive tool for studying the real-time kinetics of changes in living cells. Examples are presented for the kinetics of rapidly changing intracellular calcium detected by the calcium indicator probe indo-1 and the redistribution kinetics of multiple vital dyes placed in cells undergoing cell fusion. PMID- 2331371 TI - Rapid and sensitive detection of DNA in Southern blots with chemiluminescence. AB - A new chemiluminescent Southern blot procedure offers molecular biologists a safe, ultrasensitive and rapid alternative to conventional 32P-based systems. This new DNA detection system, SOUTHERN-LIGHT, has been developed by Tropix, Inc. The luminescent signal is produced from a direct chemiluminescent substrate, disodium 3-(4-methoxyspiro[1,2-dioxetane-3-2'-tricyclo-[3.3.1.1 .3,7]decan]-4-yl) phenyl phosphate (AMPPD), which decomposes upon dephosphorylation with alkaline phosphatase. SOUTHERN-LIGHT is an ultrasensitive, rapid detection kit for use with membrane-bound DNA. It is the first test kit to incorporate AMPPD. It requires no specialized equipment and results can be conveniently imaged on instant film or x-ray film within 5-60 min of exposure. PMID- 2331372 TI - Solution hybridization assay for detecting genetically engineered microorganisms in environmental samples. AB - A solution hybridization method was developed for detecting genetically engineered microorganisms in environmental samples. The detection method involves recovery of DNA from the microbial community of an environmental sample followed by hybridization in solution with a radiolabeled RNA gene probe. After nuclease digestion of non-hybridized probe RNA, the DNA-RNA hybrids formed in the solution hybridization reaction are separated by sephadex or hydroxyapatite column chromatography and detected by liquid scintillation counting. Using solution hybridization-gene probe detection, as few as 100-1000 target cells per gram sediment sample of a 2,4,5-T-degrading genetically engineered microorganisms could be detected. PMID- 2331373 TI - Male accessory sex glands produce heparin-binding proteins that bind to cauda epididymal spermatozoa and are testosterone dependent. AB - Heparin binds to bovine sperm and stimulates capacitation in vitro. Seminal plasma alters the ability of epididymal sperm to bind heparin, and several heparin-binding proteins (HBPs) have been identified in bull seminal plasma. This study had three objectives: 1) to identify production sites of seminal plasma HBPs, 2) to determine which HBPs bound to cauda epididymal sperm, and 3) to determine whether presence of HBPs was testosterone dependent. Proteins from bull or rat seminal vesicles, prostates, and bulbourethral glands were separated by heparin affinity high-performance liquid chromatography. HBPs were found in all accessory glands of rats and bulls, but the major source of bovine seminal plasma HBPs appeared to be seminal vesicles. Between 25% and 50% of the protein from each gland bound to the heparin column, and NaCl concentrations required to elute proteins ranged from 0.15 to 1.4 M. One-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that major HBPs were relatively small, with molecular weights between 13 and 31 kDa, but some HBPs also exhibited higher molecular weights, between 40 and 100 kDa. Radioiodinated HBPs from each bovine gland were incubated with epididymal sperm. Labeled HBPs binding to sperm exhibited molecular weights of 14, 16, 24, and 30 kDa as determined by SDS-PAGE and autoradiography. The HBP content of the accessory sex glands decreased significantly in castrated rats and was restored to levels of sham-operated controls by testosterone replacement. Heparin-binding proteins may play a role in fertilization by attaching to sperm surfaces, enabling heparin like glycosaminoglycans in the female reproductive tract to induce capacitation. PMID- 2331374 TI - Spermatogenesis-related change in the synthesis of the creatine kinase B-type and M-type isoforms in human spermatozoa. AB - We have demonstrated earlier that the per sperm creatine-N-phosphotransferase (CK) activity was increased in oligospermic vs. normospermic men. The increased sperm CK activity is related to higher concentrations of cellular CK, which may indicate a defect of cytoplasmic extrusion during spermatogenesis. In the present work, we examined whether in spermatozoa, similar to muscle, there is a change in the synthesis of B-CK and M-CK isoforms during cellular differentiation. In 109 normospermic and 50 oligospermic specimens (sperm concentrations 60.6 +/- 3.7 vs. 8.8 +/- 1.3 million sperm/ml; all values expressed as mean +/- SEM), the relative concentrations of the M-CK isoform (M-CK/M-CK + B-CK) were 27.2% +/- 2.1% vs. 6.7% +/- 0.9% (P less than 0.001). The per sperm CK activities showed comparable differences (0.21 +/- 0.02 vs. 0.89 +/- 0.1 CK IU/100 million sperm; P less than 0.001) in the two groups, and there was a close correlation between per sperm CK activities and M-CK concentrations (R = 0.69, P less than 0.001, N = 159). This indicates that the loss of cytoplasm and the commencement of M-CK isoform synthesis are related events during the last phase of spermatogenesis, also that the incidence of spermatozoa with incomplete cellular maturation is higher in oligospermic specimens. In characterizing the M-CK, we found that sperm (unlike muscle tissue) lack the MB hybrid of CK dimers. However, in the presence of muscle M-CK, the muscle-sperm MB-CK hybrid has formed. Thus in sperm and muscle the M-CK isoforms are structurally different, whereas the B-CKs are apparently homologous.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331375 TI - Ultrastructure of the sperm and spermatogenesis in five South African species of the trochid genus Oxystele (Mollusca, Prosobranchia). AB - Sperm of Oxystele are of the primitive type, which is typical of molluscs using external fertilization. They comprise a head, which is composed of a barrel shaped nucleus and large conical acrosome; a midpiece of five or six spherical mitochondria; and a tail, with a 9 + 2 arrangement of microtubules. The morphology of the sperm broadly resembles that of the sperm of other trochids as well as that of the sperm of the Pleurotomariidae, Haliotidae, and Fissurellidae but differs considerably from that of the Patellidae. Each of the five species examined was found to have a different sperm morphology. Our results support the suggestion of Heller and Dempster (in preparation) that Oxystele variegata Anton actually consists of two sympatric species. The morphological changes that occur during spermatogenesis are very similar in all species and resemble descriptions given for other molluscs with primitive sperm. PMID- 2331376 TI - Activation of mammalian oocytes by a factor obtained from rabbit sperm. AB - In this study a fraction was prepared from rabbit sperm that activated rabbit and mouse oocytes following injection into the cytoplasm. The sperm factor activated oocytes exhibited cortical granule exocytosis, pronuclear formation, and cleavage. The sperm factor was soluble in aqueous solution and was not active extracellularly. Unlike most artificial activation methods that are only effective with aged oocytes, the sperm factor activated recently ovulated oocytes. The factor appears to be a protein or associated with a protein but not an acrosomal protein. Fractions from both mouse and bull sperm did not activate rabbit or mouse oocytes. Their inactivity may be owing to the techniques used to recover the fractions or differences between species in sperm morphology and fertilization processes. These observations support the hypothesis that oocyte activation is induced by a factor within sperm that is released into the cytoplasm of the oocyte at the time of sperm-oocyte fusion. PMID- 2331377 TI - Protamine amount and cross linking in mouse teratospermatozoa and aneuploid spermatozoa. AB - The level of SH-group oxidation in spermatozoa from the cauda epididymis was measured by a cytofluorometric method in chromosomally normal mice and two chromosome mutants. The first one, a tertiary trisomic karyotype (Ts(1(13]7OH), is characterized by severe oligospermia and high levels (approximately 75%) of malformed spermatozoa. The second, a hybrid between two European feral mouse stocks, is heterozygous for multiple Robertsonian translocations and produces exclusively aneuploid spermatozoa. Neither the severe teratospermiogenesis nor the severe aneuploidy was reflected in total SH-group fluorescence values nor in free SH-group fluorescence. It is concluded that both the production of protamines and protamine cross linking by S-S bridge formation are rather autonomous processes during spermatogenesis because 1) the increased DNA variance of the aneuploid spermatozoa is not reflected in an increased variance of the total and free SH-groups, 2) aneuploidy for the protamine gene carrying chromosome 16 is not reflected by the SH-group values for individual spermatozoa, and 3) protamine production and cross linking are independent of the mild to severe terataspermiogenesis in the tertiary trisomic karyotype. PMID- 2331379 TI - Cardiovascular system. PMID- 2331378 TI - Molecular cloning of an acrosomal sperm antigen gene and the production of its recombinant protein for immunocontraceptive vaccine. AB - A monoclonal antibody, HS-63, which reacts specifically with a highly conserved sperm acrosome antigen, was shown to inhibit in vitro fertilization of mouse and human. The corresponding sperm antigen designated as MSA-63 was purified to homogeneity from mouse testes and used as an immunogen to generate polyclonal antisera in rabbits. The cDNA fragments of MSA-63 gene were cloned from mouse testis cDNA library by an immunoscreening method using polyclonal antisera specific for MSA-63. Using the established cDNA clone as a probe, the gene encoding for MSA-63 protein was found to be conserved among different mammalian species. Only one specific mRNA 1.5 kb in size was identified from the adult mouse testis among different mouse tissues. The recombinant fusion protein containing MSA-63 protein fragment was produced in Escherichia coli and used to immunize female mice. Similar to the original HS-63 monoclonal antibody, the antisera thus produced reacted only with the sperm acrosome and revealed significant inhibition to the in vitro fertilization of mouse oocytes. The results of this preliminary study suggest that it is feasible to mass produce sperm-specific antigens or their antigenic fragments by recombinant DNA technology for the development of sperm antigen-based immunocontraceptive vaccines. PMID- 2331380 TI - Three-dimensional magnetic resonance imaging. AB - Three-dimensional surface reconstruction images of the heart and great vessels can be produced from contiguous sequences of ECG-triggered MR scans in patients with congenital heart disease. The methods allow separation of the epi- and endocardial surfaces and definition of the enclosed blood volumes on a slice-by slice basis. Surface reconstruction images have value in communicating the results of MR examinations to clinicians in cases where cardiac morphology is unusually complex; in depicting intracardiac defects, size, and location; and in aiding the study of pulmonary venous drainage. This method can be practical in studying cardiac morphologic abnormalities and especially in planning cardiac surgery. PMID- 2331381 TI - New directions in cardiac magnetic resonance imaging. AB - Cardiac MRI is poised for a major change: Recent development of echoplanar imaging, or "instant" scanning, offers the possibility of studying myocardial perfusion with contrast agents. Moreover, newer contrast agents are being developed to study various aspects of myocardial function. Techniques of MR angiography have progressed: Noninvasive coronary angiography for detecting asymptomatic atherosclerosis of at least the proximal region of the coronary arteries appears possible in the near future. MRI has also been used to solve a long-standing problem in cardiac imaging: the absence of point-to-point correspondence in tomographic images of the heart from diastole to systole. Through tissue tagging, MRI offers the unique possibility of noninvasively assessing local and regional ventricular deformation more accurately than any other method available today. PMID- 2331382 TI - Chest wall reconstruction after resection of primary malignant chest wall tumours. AB - In order to review the development of chest wall reconstruction, 37 cases of primary malignant skeletal chest wall tumours treated since 1958 were studied. These included chondrosarcomas (20), Ewing's tumours (7) and solitary plasmacytomas (10). Skeletal reconstruction was performed in 24 patients. Before 1972, Marlex mesh alone was used. Since then, a sandwich of two layers of Marlex mesh with a filler of methyl methacrylate was utilised successfully producing better functional and cosmetic results. Primary soft tissue closure was possible in all but 5 cases in whom latissimus dorsi myocutaneous flaps were used. All but one patient had an uneventful postoperative recovery with none requiring postoperative ventilatory support. The overall survival of 46% at 5 years and 27% at 10 years was encouraging. Familiarity with the techniques of chest wall reconstruction enables wide excision of primary chest wall tumours and the palliation and treatment of other malignant, infective and degenerative conditions since even large defects can be reconstructed with little functional disturbance. PMID- 2331383 TI - Thoracic aneurysm in association with an aberrant right subclavian artery. AB - A case of a 45-year-old man is presented with clinical signs of a dissecting aortic aneurysm. Angiography and CT demonstrated a dissecting thoracic aneurysm (deBakey type III a) and an aberrant right subclavian artery arising from this aneurysm at the fourth branch of the aortic arch. In the first step, the aberrant artery was implanted into the right common carotid artery. In a second operation, the aneurysm was replaced by a Dacron tube. The advantage of our procedure is the perfusion of at least one vertebral artery during aortic cross-clamping and easier access to the aneurysm through a left thoracotomy. As far as we know, this is the fourth presentation of such a case in the literature in which the other cases concern angiographic or post-mortem findings. PMID- 2331384 TI - Coronary artery bypass with inverted internal mammary artery: angiographic evidence of late graft patency. AB - The internal mammary artery (IMA) is currently considered as the graft of choice for myocardial revascularization procedures. We report on two patients who underwent successful coronary artery bypass surgery using retrograde IMA flow. We provide, for the first time, angiographic evidence of late patency of an inverted IMA graft. PMID- 2331385 TI - Coronary artery spasm following coronary artery bypass grafting. Treatment with intracoronary ISDN followed by systemic intravenous nifedipine infusion. AB - Coronary artery spasm following coronary artery bypass grafting (CABG) has been described previously. The cause and underlying risk factors are mainly speculative and treatment therefore symptomatic. We present the successful management of this condition by administration of an intravenous Nifedipine infusion after intracoronary Isosorbide dinitrate (ISDN) had failed to relieve the spasm. PMID- 2331386 TI - Tracheobronchial mucoepidermoid carcinoma in childhood with a ten year follow-up. AB - Tracheobronchial mucoepidermoid carcinoma in childhood is extremely rare. The patient described was treated by pneumonectomy and is the third reported with a long-term follow-up. The pathology, surgical options and the past experience with this tumour are reviewed. PMID- 2331387 TI - A newly designed venous cannula for use during total cardiac bypass in the closed chest by femoro-femoral perfusion. AB - A two-staged venous cannula was developed for total cardiac bypass in the closed chest during femoro-femoral perfusion. This was as effective as the dual cannula system. Its use is advocated in repeat open heart surgery. PMID- 2331388 TI - United Europe: a challenge for the Association. PMID- 2331389 TI - The science of cardiac surgery. PMID- 2331390 TI - Internal mammary artery: methods of use and their effect on survival after coronary bypass surgery. AB - Hazard analysis of total and cardiac mortality after isolated primary coronary artery surgery was performed using univariate and multivariate methods with special emphasis on the importance of the use and method of use of the internal mammary artery (IMA) as a bypass graft. The clinical data of 5880 consecutive patients were studied. The sum of the real follow-up periods studied was 27,948 years. The hazard of total and cardiac mortality could be defined in three-phase parametric models with an early, a constant and a late phase. The total survival was 82% +/- 1% at 10 years and 59% +/- 3.6% at 15 years. The construction of a single IMA distal graft (using left or right IMA) had a positive influence on the hazard (P = 0.0004) in the late phase after surgery with a high estimate (-1.6). The cardiac survival was 89% +/- 0.8% at 10 years and 74% +/- 3.5% at 15 years. The use of the left IMA had a positive influence (P = 0.001) in the late phase after surgery with a very high estimate (-2.3). The generated simulation of the total survival of a median patient with an IMA graft is 97% at 5 years and 94% at 10 years; for a median patient without an IMA graft, it is 97% at 5 years and 88% at 10 years. If a patient has other risk factors reducing his life expectancy, the influence can be dissipated because of lower survival rates at 5 years after surgery, when the effect of the IMA becomes most apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331391 TI - Diagnosis of perioperative myocardial necrosis following coronary artery surgery- a reappraisal of isoenzyme analysis. AB - Although the routine determination of CK-MB activity is widely used after coronary artery bypass grafting (CABG), the diagnosis of a perioperative myocardial necrosis remains arbitrary. The intention of the present study was to develop discriminative enzymatic parameters of CK-MB activity in a collective of 710 patients following CABG. Patients were grouped according to their postoperative electrocardiogram (ECG). For each patient, the time activity curve of CK-MB was determined. The total amount of CK-MB was calculated by integrating the area beneath the CK-MB activity curve. Patients presenting with an unchanged postoperative ECG (group I) or a new bundle branch block with uncompromised haemodynamics (group IIa) had an uniform and low profile of CK-MB activity. Serial CK-MB activities as well as the integrated CK-MB area of these two collectives were significantly different (P less than 0.001) from values determined for patients with bundle branch block and low cardiac output (group II b) or patients with new Q waves (group III). After 24h, the 90th percentile of serial CK-MB activities of group I had declined to 18 U/l and was clearly exceeded by 90% of all patients that belonged to either group IIb or III. The 90th percentile of CK-MB areas for group I showed a value of 801 U/l x h. CK-MB areas above 801 U/l x h were seen in about 50% of all patients of group IIa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331392 TI - Relevance of anatomopathology of high oesophageal strictures to the design of surgical treatment. AB - From 1971-1987, inclusive, 407 patients with oesophageal stricture were operated on by one surgeon. Of these, 116 were found to have high oesophageal stricture and form the basis of this presentation. Every patient had the usual clinical, radiological and endoscopic examinations with biopsies taken above, at, and (when possible) below the stricture. At operation, the surgical anatomy and pathology of the oesophagus and mediastinum were determined and the site of the peritoneal reflexion and its relation to the stricture were noted. In those resected, the resected specimen was examined histopathologically. Thus clear aetiopathology could be established and this was correlated with the type of operation. Postoperatively, patients were followed up regularly. Results showed that high strictures were of four definite types: (1) reflux strictures with short oesophagus (n = 90) of whom 52% required resection and 48% had conservative surgery, (2) caustic and other non-reflux strictures (n = 10) all of whom required resection, (3) Barrett-type strictures (n = 8) all treated by conservative surgery, (4) idiopathic strictures (n = 8) of whom half required resection because of suspicion of malignancy. The study indicated that the rational basis for the design of surgery is to ascertain the aetiopathology which can only and finally be determined at operation. PMID- 2331393 TI - Indium 111 imaging in appendicitis. PMID- 2331394 TI - [The proposed classification of epilepsies and epileptic syndromes (1989) and its clinical significance]. AB - The development of a rational approach and prognostication of epilepsy is based on a special profile of seizure events or the suggested diagnosis of a specific disorder. Although classifications based on neurobiological knowledge would be highly desirable, the present state of inadequate information makes such task difficult. Current classification schemes are, therefore, based on clinical signs and symptoms which are readily identifiable. The significant progress of epileptology has brought us to the stage where one can delineate a number of epileptic syndromes, provide a precise definition, and orient individual syndromes. With further accumulation of both clinical experience and new knowledge in neurosciences, the proposed classification will develop to more appropriate schemes. PMID- 2331395 TI - [Special application of EEG and evoked potential studies for practice of childhood epilepsy]. AB - The patients whose EEG demonstrates spikes in the midline-parietal, left and/or right centro-parietal areas can be belonged to a category of benign epilepsy in childhood. In these patients, an extremely high voltage somatosensory evoked potential (SEP) mimicking a spike is elicited by electric stimulation to both upper and lower extremities. The peaks of this giant SEP show extraordinarily high amplitude at N32 and at N50 by stimulation to median and posterior tibial nerves, respectively. It is thought that these spikes originate from the somatosensory cortex in the light of the latencies of the giant SEP. It is not uncommon that the infants with perinatal problems show insufficient staring and tracking. Among these infants, those who have occipital irregular polyspikes and slow waves later develop infantile spasms. This unique combination may be important as the high risk signs of infantile spasms. The visual outcome of these patients relates to persistence of seizures and discharges rather than the pattern of visual evoked potential. PMID- 2331396 TI - [The new cassette EEG recording system: its application to epileptic children]. AB - We designed a new cassette EEG recording system which consists of a recording block (an ambulatory-type data recorder and a newly developed pre-amplifier) and a reproduction block (a fixed-type data recorder, a personal computer equipped with A/D converting board and an intervening EEG device for a bandpass filter). This system was applied to 36 epileptic children, and 33 ictal records were obtained. The seizure type could be precisely classified by a comparative analysis of the data computed from this system and from the ictal symptoms. Three representative cases were presented with actual analysis procedures. PMID- 2331397 TI - [Epilepsy and sleep: with special reference to nonconvulsive status epilepticus with continuous diffuse spike-waves during slow-wave sleep]. AB - There are numerous important problems concerning relationship between epilepsy and sleep. To clarify the clinical significance and pathophysiology of the nonconvulsive status epilepticus with continuous diffuse spike-waves during slow wave sleep (CSWS) in EEG, this study was carried out on seven cases each of epilepsies with electrical status epilepticus during slow sleep (ESES) and with peculiar type of nonconvulsive status epilepticus in childhood (PNSE) and four cases of atypical benign partial epilepsy (ABPE). Mental deterioration was most frequently observed in ESES, less in PNSE but none in ABPE. In both ESES and PNSE, mentally deteriorated cases showed suppression of CSWS at significantly later ages than those without deterioration. And spike-wave indices during slow wave sleep, which were the highest in ESES and lower in PNSE and ABPE, also had a strong relation to mental deterioration. In these three disorders, both clinical seizures and CSWS were suppressed at or before 16 years of age, although they were intractable before adolescence. This finding indicated age dependent evolutions of the three disorders. Coherence and phase analysis of CSWS was undertaken to differentiate primary and secondary bilateral synchrony in seven cases of these three disorders, which have both features of generalized and partial epilepsies. This analysis disclosed secondary bilateral synchrony as the nature of CSWS in six cases. And this analysis method was considered to provide a clue to their pathophysiology. Thus, in these disorders, importance of early diagnosis by EEG including deep sleep and early treatment was recognized. PMID- 2331398 TI - [Effects of neonatal hypothyroidism on brain development: analysis of brain metabolites using high resolution phosphorus and proton magnetic resonance (NMR) spectroscopy]. AB - The brain metabolites were studied in the neonatal hypothyroid rat brain using 31P and 1H nuclear magnetic resonance (NMR) spectroscopy. In vivo 31P spectroscopy of the brains in hypothyroid rats showed the tendency of decrease in phosphocreatine/Pi and phosphocreatine/ATP ratio, suggesting suppressed brain energy status. On proton analysis using perchloric acid extracts of the brain, 10 metabolites were easily recognized. Quantitative analysis of individual metabolites revealed decreased contents of GABA, NAA (N-acetyl aspartate) and phosphocreatine and increased contents of taurine in hypothyroid rat. It was concluded that NMR is a useful and promising tool to evaluate brain metabolites. PMID- 2331399 TI - [Assessment of lumbar trabecular bone density by means of single energy quantitative CT in hospital control children and bone metabolic disorders. 1]. AB - We studied the 3rd lumbar vertebral trabecular bone mineral density in 59 cross sectional pictures of quantitative computed tomography (QCT) with CaCO3 phantom for 28 hospital control children and 30 cases of suspected bone metabolic disorders. The QCT value of bone mineral density of control children showed neither age dependency nor sexual difference before puberty: for males was 221.8 +/- 30.2 mg CaCO3/cm3 (Mean +/- SD) under 4 years, 218.1 +/- 39.7 at 5-9 years and 217.2 +/- 30.9 at 10-15 years; and for females 220.9 +/- 18.3 under 4 years and 240.0 +/- 29.4 at 5-9 years. The QCT values of bone mineral density in bed ridden patients, children receiving glucocorticoids and children receiving anticonvulsants were significantly lower than that in control children (p less than 0.005). The QCT value of bone mineral density of bed-ridden patients was significantly lower than that of children receiving glucocorticoids and of children receiving anticonvulsants (p less than 0.05, p less than 0.005 respectively). Our study confirmed that single energy quantitative CT was very useful in pediatric clinical application. PMID- 2331400 TI - [A case of neonatal herpes simplex virus encephalitis with calcifications of thalamus and basal ganglia]. AB - A male infant developed left-sided myoclonus associated with low grade fever at 21 days of age. The course of pregnancy and delivery had been uneventful. Birth weight was 2,240g at 38 weeks of gestation. Physical examination at 26 days of age revealed hyperirritability and incomplete Moro reflex. EEG showed periodic discharges originating in the right central region. Initial brain CT at 26 days of age showed no apparent abnormality. In lumbar CSF protein was 173 mg/dl, and nucleated cells 328/mm3 (polynuclear cells 6 and mononuclear cells 322). Cultures of CSF for bacteria and viruses were negative. Although, the serum titers of CF antibody to herpes simplex virus (HSV) were 1:4 to 1:8 during hospitalization and those in CSF were not increased significantly, ELISA titers for IgG and IgM in serum and CSF rose significantly. The diagnosis of HSV encephalitis was made at 41 days of age. His myoclonus was well controlled with phenobarbital and clonazepam. He was treated with acyclovir and CSF findings returned to normal. On 2nd brain CT (39 days of age), calcification at thalamus, basal ganglia and right frontal lobe, which is extremely rare CT findings for HSV encephalitis, was noticed. His DQ at discharge was about 90. It is emphasized that the early diagnosis of HSV encephalitis can be made by ELISA and serial brain CT examinations, and that HSV encephalitis should be considered when calcification of thalamus and basal ganglia are detected on brain CT. PMID- 2331401 TI - [A case of aplastic anemia induced by phenobarbital]. PMID- 2331402 TI - [Giant somatosensory evoked potentials in Rett syndrome]. PMID- 2331403 TI - [CT appearances in a neonate presenting with seizures; a neoplastic lesion or hemorrhagic infarction?]. PMID- 2331404 TI - A controlled model of moist wound healing: comparison between semi-permeable film, antiseptics and sugar paste. AB - An established wound model in the pig has been modified using a Stomahesive ring to enable study of the effects of fluids used in wound care. Full thickness wounds (up to 9 mm deep) were treated with the substances under test. Each application was held in place with a Stomahesive flange, the inner part of which had been excised as far as the hard plastic ring. All dressings were then covered with OpSite which allowed gaseous exchange whilst retaining treatment fluids and secretions. Wounds were treated immediately and at 2 and 4 days. The experiment was terminated after 7 days and the whole wound, with dressing, was excised for histological examination. The wounds covered with OpSite alone and those treated with sugar paste under Opsite were found to be infilled with granulation tissue over which epidermal migration was taking place. Those wounds which had been packed with gauze, to which had been added one of the following: chlorhexidine gluconate 0.2%, Irgasan 0.2%, povidone iodine 0.8% or EUSOL half-strength, showed delayed healing in that less infilling had taken place over the same time period. This delay could be attributed to the nature of the chemicals used and/or the influence of gauze packing. This delay in the healing of wounds treated with chemical agents was least with EUSOL half-strength and greatest with chlorhexidine. No toxic effects were observed with sugar paste which may be preferable to antiseptics for the management of dirty or infected wounds. PMID- 2331405 TI - The effect of prostaglandins on experimental storage disease in rats. AB - The aim of this study was to investigate the effect of prostaglandins (PGs) on the release of lysosomes into the extracellular space in experimentally-induced storage disease in rats. The generalized phospholipidosis was induced by oral administration of chlorphentermine to Wistar rats. PG-E2 or PG-F2 alpha (50 micrograms/100 g) was injected intravenously into rats with phospholipidosis. Control rats were injected with the same amount of saline. Twenty-four hours later, extracellular and intracellular lysosomes were analysed morphometrically in electromicrographs of the liver, kidney, myocardium, skeletal muscle, aorta and cervix uteri, having been stained with acid-phosphatase. The morphometric parameters used were the numerical density of lysosomes per unit volume and the volume density of lysosomes per unit volume. The results show that, in comparison with the controls, a volumetric increase of extracellular lysosomes and a volumetric decrease of intracellular lysosomes were achieved by PG-E2 or PG-F2 alpha administration in several organs, but not in the myocardium or skeletal muscles. The effect of PG-F2 alpha was greater than that of PG-E2 in the liver and kidney, while the effect of PG-E2 was greater than that of PG-F2 alpha in the aorta and cervix uteri. These results indicate that PGs influence the discharge of storage lysosomes in bipolar epithelial cells in the liver and kidney, and also influence the release of non-storing lysosomes in apolar mesenchymal cells in the aorta and cervix uteri. PMID- 2331406 TI - Lipid extraction attenuates the calcific degeneration of bovine pericardium used in cardiac valve bioprostheses. AB - Bovine pericardial bioprostheses frequently fail due to dystrophic calcification. Since (a) recent studies indicate that membrane-associated complexed acidic phospholipids play an important role in the process of both physiologic and pathologic calcification, and (b) cytoplasmic organelles and plasma membrane of interstitial cells seem to serve as initial sites of calcific degeneration of bioprosthetic bovine pericardial tissue, this investigation was undertaken to evaluate whether, and if so, to what extent, the mineralization of valve tissue could be attenuated by previous lipid extraction. Pretreatment of glutaraldehyde preserved bovine pericardium with acidified sulphuric ether (pH 3.0-4.0) attenuated calcification significantly: 28 days after subcutaneous implantation in young rats the degree of mineral deposition was approximately equal to typical 7 days implants in this model. The mechanism of this beneficial effect is suggested to be due to partial extraction of tissue phospholipids, as demonstrated by electron microscopy, thus reducing the number of available sites for deposition of hydroxyapatite crystals. In addition, and importantly, the present results indicate that any attempt to reduce cardiac valve bioprosthesis mineralization will have to take into account the role of lipids and, particularly, the membranous phospholipids in the calcification mechanism. PMID- 2331407 TI - Characterization of skin lesions in mice following intradermal inoculation of Haemophilus ducreyi. AB - Twelve strains of H. ducreyi, which included two reference strains, were each inoculated intradermally into the flanks of CBA mice. All strains produced self limited lesions which were macroscopically and microscopically typical of those seen in chancroid. Pustular nodules, about 5mm in diameter, developed at all inoculation sites by the second day when 10(7) organisms were inoculated. Approximately half of these lesions ulcerated and all had regressed by 2 weeks. Smaller nodules developed at about half the sites from the second to the fifth day when 10(6) or 10(5) organisms were given, but these did not ulcerate. No lesions were seen when 10(3) organisms were inoculated. Organisms were recovered from the lesions up to 11 days after inoculation. Specific H. ducreyi antigen, sought by a monoclonal antibody test, was detected in lesions up to 15 days following inoculation. Heat-killed organisms of H. ducreyi also produced nodules and ulcers although these were slightly smaller than those which developed after inoculation of viable bacteria. Similar lesions to those caused by H. ducreyi were produced after intradermal inoculation of about 10(8) viable or killed Neisseria gonorrhoeae organisms. Treatment of mice with ceftriaxone had little or no effect on the subsequent development of H. ducreyi-induced lesions. These findings indicated that the lesions were not produced specifically by viable H. ducreyi organisms. Ulcers were also produced following intradermal inoculation of purified lipopolysaccharide (LPS) from H. ducreyi or N. gonorrhoeae, but not by cell-free filtrates prepared from H. ducreyi cultures indicating a possible role for LPS in the pathogenesis of ulcerative skin lesions. PMID- 2331408 TI - Ultrastructural correlates of ischaemic contracture during global subtotal ischaemia in the rat heart. AB - The development of left ventricular ischaemic contracture and its correlation with ultrastructural and sarcolemmal permeability defects were studied in isolated rat hearts during global subtotal ischaemia. With acetate as substrate the hearts exhibited a rise in diastolic tension after 8-10 min at which time small foci of contracted myocytes were scattered throughout the myocardium. In hearts with 5% of the maximum diastolic tension (termed 5% contracture), the foci were situated predominantly in the subendocardium and papillary muscle. Contracted myocytes in these foci were capable of excluding ionic lanthanum thus demonstrating retention of normal sarcolemmal permeability properties. With 30% contracture ultrastructural damage had spread to the subepicardium and with further contracture there was an associated increase in the number and size of foci in all regions. In these foci, swelling of the tubular sarcolemmal system and occasionally of the sarcoplasmic reticulum appeared to precede myofibrillar contraction. At 50% contracture lanthanum influx into contracted cells became more frequent. Hearts developed full contracture by 15-18 min at which time most myocytes were contracted and retained lanthanum intracellularly. The heterogeneity of the response at a cellular level may offer a possible explanation for the lack of correlation between contracture and tissue ATP. A possible sequence of structural injury leading to impaired calcium homeostasis is also suggested. PMID- 2331409 TI - Fibrin deposition and adaptive changes in glomerular procoagulant and fibrinolytic activities in rat renoprival nephropathy. AB - To investigate the mechanisms which may influence fibrin deposition in the remnant kidney, glomerular morphology and the haemostatic properties of isolated glomeruli were assessed in two groups of rats, 30 days after surgical removal of three-quarters of the total renal parenchyma, and compared to glomeruli in sham operated controls. One group was given the thromboxane synthetase inhibitor OKY 046 and the other was not. Fibrin deposition occurred in about 20% of glomeruli, of which 4% exhibited segmental necrotizing lesions. Concomitantly, glomerular procoagulant activity dropped to 40% of the control level and glomerular fibrinolytic activity rose to 120-130% of this level. Inhibition of thromboxane synthesis did not affect fibrin deposition, glomerular haemostasis or the development of renal insufficiency. In an additional group of unilaterally nephrectomized rats, procoagulant activity also markedly decreased in the remaining kidney. These results indicate that in the rat remnant kidney, alterations in glomerular haemostatic properties tend to have antithrombotic effects which seem to constitute an adaptive reaction by an autacoid system to glomerular fibrin deposition. PMID- 2331410 TI - Experimental osteoarthritis in guinea-pigs. AB - Cartilage degeneration was induced in the hind knees of guinea-pigs by surgery. Partial medial meniscectomy induced rapidly progressing lesions whereas the lesions induced by section of the lateral collateral ligament with or without section of the medial collateral ligament developed later and progressed more slowly. In all cases the lesions were first seen focally on the medial tibial plateau where they extended both laterally and deeper into the cartilage. Later, lesions appeared on the medial femoral condyle and meniscus, and eventually also on cartilage in the lateral joint compartment. During the later stages, these models had many features of human osteoarthritis. The appearance and progression of spontaneous lesions in the hyaline cartilage of the hind knees of young guinea pigs first reported by Bendele and Hulman (1988) has been confirmed. Extra ascorbic acid added to the drinking water had a slight chondroprotective effect on the development of spontaneous lesions but gave no significant protection against the development of lesions induced by lateral collateral ligament section. PMID- 2331411 TI - Advocacy for children. PMID- 2331412 TI - Congenital teratomas of the neck and nasopharynx: a clinical and pathological study of 18 cases. AB - Congenital teratomas of the neck and nasopharynx are unusual tumours that seldom metastasize. Due to their rarity, reviews often have relied upon compilations of isolated case reports. We report our experience of the early outcome of 18 cases (14 cervical, four nasopharyngeal) to demonstrate the high morbidity and mortality that these benign but critically placed lesions have because of local mass effects. Six patients (33%) either were stillborn or died of disease within 2 days of birth; of the survivors, four (22%) had significant respiratory obstruction requiring surgery. Tumour location and size rather than histologic grading were the most significant features affecting the immediate clinical course. All but one of the patients who underwent early surgical resection had a favourable outcome. PMID- 2331413 TI - Five cases demonstrating the distinctive behavioural features of chromosome deletion 17(p11.2 p11.2) (Smith-Magenis syndrome). AB - Children with hyperactivity and self-destructive behaviour present a difficult problem for parents and paediatricians. The syndrome described by Smith and Magenis is due to a deletion on the short arm of chromosome 17: del(17)(p11.2 p11.2). Clinical manifestations include brachycephaly and a flat mid-face; brachydactyly; short, broad hands; mental retardation; and aberrant behaviour, including hyperactivity. We report on five children, and review the literature on a newly recognised syndrome in which the behaviour manifestations may precede and often overshadow the learning disabilities and unusual appearance. In addition, we have found sleep disturbance to be a major feature in our patients. PMID- 2331414 TI - Sexually abused adolescents: a distinct group among sexually abused children presenting to a children's hospital. AB - Case records were retrospectively reviewed for 40 adolescents presenting to a paediatric sexual abuse service with a history of acute (23 cases) or chronic (17 cases) abuse. The chronic cases disclosed the abuse to a family member, the abuse was intrafamilial, and they had similarities to the chronically abused younger child. The acute cases disclosed the abuse outside the family, and were abused by strangers or acquaintances. Some acutely abused adolescents had similarities to child victims of stranger assault; however a larger sub-group was identified (14 of 23; 35% of total) whose indescriminate behaviour may have placed them at increased risk of abuse. They were characterized by previous contact with police and welfare agencies, alcohol/drug abuse, voluntary sexual activity, contraceptive use, genital infections and apparent indifference to the abuse. Half the total group felf emotionally unsupported, and four subsequently attempted suicide. This study identifies unique problems of sexually abused adolescents, and recognizes potential multiple problems in those acutely abused. PMID- 2331415 TI - Paediatric post-injury management: a hospital-based review of deaths. AB - In order to begin to evaluate the need for an integrated trauma management service for injured children, a retrospective review of deaths following admission to a suburban teaching hospital was conducted. The medical records and coroners' reports for 64 consecutive cases over 68 months were reviewed, looking for errors in care which may have contributed to fatal outcomes. There was a male predominance (64%). The main causes of death were pedestrian injuries (42%), drownings (20%), injuries to vehicular passengers (17%) and injuries to cyclists (13%). Errors, often multiple, occurred in 29 cases (45%). Errors most frequently involved airway control and ventilatory support (25%), volume replacement (19%) and delays in performing essential investigations (13%). Errors were most frequent at the referring hospitals (49% [17 of/35 referred cases], compared with 14% at the teaching hospital), and principally involved multiply injured victims of blunt trauma (81%, 13 of 16 patients). In only three cases (5%) would better management have salvaged the patient. This can be explained partly by the predominance of what were judged to be irretrievable intracranial injuries (90%) in patients suffering blunt injuries. In contrast, an analysis of the same patient group revealed that in 30-50% the fatality could have been prevented by the full application of well recognized safety strategies. While strategies such as triage and trauma teams should reduce the error rate, it is yet to be proven that optimal post-injury care will significantly reduce mortality. PMID- 2331416 TI - Malnutrition in cystic fibrosis: psychosocial functioning of patients and their families. AB - The relationship between nutritional status and psychosocial functioning was examined in 35 children with cystic fibrosis, aged 7-16 years. Twelve malnourished children and their families were compared with 23 well nourished children and their families. Established measures of adjustment and coping in the children, parents and families were used. Few statistically significant differences between the two groups emerged, and all comparisons of psychosocial functioning were not significant. The results of the study suggest that there is no relationship between the nutritional status of the child with cystic fibrosis and the current psychosocial adjustment and coping of child, parents and family. PMID- 2331417 TI - The weight control practices of 15 year old New Zealanders. AB - More than 800 15 year old members of the Dunedin Multidisciplinary Health and Development study cohort completed a questionnaire designed to provide descriptive data concerning the weight control behaviours of this sample of New Zealand adolescents. The results showed that approximately 75% of the adolescents were within acceptable body mass index ranges. However 68% of the girls (but only 19% of the boys) wanted to weigh less than their present weight. Generally, girls were more concerned about their body weight than boys: 26% of girls weighed themselves fortnightly or more often, compared with 12% of boys; 45% of girls reported that they were trying to lose weight at present, compared with 9.5% of boys. The main methods of weight reduction included weight reduction diets (21% of girls, 4% of boys in the previous year); exercise such as jogging, walking, swimming and cycling (60% of girls, 34% of boys); and participation in dieting and fitness clubs (35% of girls, 16% of boys). In addition, 20% of girls reported using techniques such as slimming tablets (3%), cigarette smoking (5%) and self induced vomiting (5%) to control weight. The results show that weight control is a major preoccupation of many girls and some boys. Results are discussed in relation to differential social influences on the sexes, and health consequences. PMID- 2331419 TI - Headache activity in children and adolescents. AB - We examined headache activity in 900 Australian youth aged 10-18, using a self report questionnaire. Headache prevalence, duration, severity, symptomatology and precipitants were examined, as well as the self-statements and coping responses of children. Headaches were experienced by most children, and girls reported more frequent headaches than boys. Common headache symptoms included those traditionally associated with muscle-contraction headache and migraine. Some children reported that they found headaches to be a terrible experience and 'wished they would die' during a headache. Of the various coping responses that were endorsed, the use of medication was the most frequent. Methodological problems include the reliability and validity of self-report data, and the limitations of cross-sectional investigations. PMID- 2331418 TI - Antibody response of 18 month old children 1 month and 18 months following Haemophilus influenzae type b vaccine administered singly or with DTP vaccine. AB - Seventy-six children (aged 17-19 months) received 10 micrograms of Haemophilus influenzae type b polyribosyl-ribitol phosphate (PRP) vaccine, diluted with either phosphate-buffered saline (PBS) or diphtheria-tetanus-pertussis (DTP) vaccine, in a single-blind randomized trial. There were few side effects when PRP was administered alone. Before vaccination 37 of 76 children (49%) had non protective antibody levels (less than 0.15 micrograms/mL); 26 of these 37 (70%) achieved antibody levels of greater than 0.15 micrograms/mL 1 month after vaccination. Before vaccination 16 of 76 (21%) had antibody levels of greater than 1.0 micrograms/mL; 1 month after vaccination 39 of 76 children (51%) achieved levels of greater than 1.0 micrograms/mL. Of 12 infants who had antibody levels less than 0.15 micrograms/mL 1 month after immunization, 10 had protective levels 18 months later. Administration of PRP mixed with DTP did not affect antibody response to PRP. The potential use and limitations of PRP vaccine are discussed. PMID- 2331420 TI - Early neonatal hyperkalaemia in the extremely premature newborn infant. AB - The incidence of hyperkalaemia in 43 consecutive infants born at less than 28 weeks gestation and cared for in our neonatal intensive care unit was documented. Plasma K levels were related to indices of renal function as well as to the degree of illness in the infants. The mean gestational age was 26.0 weeks (range 24-27 weeks) and the mean birthweight was 815 g (range 395-1170 g). Twenty-six of the infants (60%) had at least one plasma K greater than 5.5 mmol/L and 13 (30%) had a maximum plasma K greater than 7 mmol/L. The mean postnatal age at which the plasma K exceeded 7 mmol/L was 25 h (range 10-39 h). Five infants with plasma K greater than 7 mmol/L developed cardiac arrhythmias and four died of this complication. Only one infant had a large intraventricular haemorrhage. Only two of 16 infants with an initial plasma K less than 5 mmol/L had a maximum plasma K greater than 7 mmol/L, compared with eight of 10 with an initial plasma K greater than 6 mmol/L (P less than 0.005). Plasma K also correlated directly with plasma urea (P less than 0.001) and plasma creatinine (P less than 0.025), and inversely with urine volume (P less than 0.05). Plasma K did not correlate with K intake, arterial pH, presence of asphyxia, severity of respiratory illness, gestation or birthweight. The rapidity with which the plasma K concentration reached potentially hazardous levels in some infants makes it imperative to measure plasma K within 6 h of birth and to continue to monitor levels at least every 6 h for the first 48 h in all infants born at less than 28 weeks gestation. PMID- 2331421 TI - Superior vena caval thrombosis in a child: an uncommon presentation of idiopathic dilated cardiomyopathy. AB - A nine year old girl who presented with a thrombosis of the right internal jugular vein and superior vena cava was found to be in cardiac failure and to have a dilated cardiomyopathy. After transient improvement she deteriorated and was accepted for cardiac transplantation. Following transplantation her condition has been much improved. PMID- 2331422 TI - Convulsion associated with fever following hepatitis B vaccination. PMID- 2331423 TI - Whooping cough vaccine. PMID- 2331424 TI - Aluminum concentrations in infant formulae. AB - The aluminum concentrations in breast milk and in 25 commercially available infant formulae were measured. The mean concentration in breast milk was 49 micrograms/L while concentrations in most of the humanized formulae were less than 500 micrograms/L. Higher concentrations were found in Nan, Prem Enfamil and the three soya formulae. We suggest that all formulae have the potential to be contaminated with aluminium, and to varying degrees in different batches. Until it is known whether aluminium toxicity occurs in normal infants fed these formulae, it seems reasonable to expect manufacturers to routinely measure aluminium and keep aluminium contamination to a minimum. This may be especially important for formula fed to infants with compromised gastrointestinal and renal systems. PMID- 2331425 TI - Premenopausal bone loss in the lumbar spine and neck of femur: a study of 225 Caucasian women. AB - Two hundred and twenty-five premenopausal women were studied to evaluate age related changes in trabecular bone mass. Measurements were made at the lumbar spine and femoral neck by dual photon absorptiometry. It was found that spinal bone density increased significantly from the 20s to reach a peak in the mid-30s. Identical trends were observed in total bone mass and bone mass normalized by length. Bone loss then proceeded at a rate of 1% per year, and by the early 50s, 10% of peak spinal density was lost. There was no peak in femoral neck density; loss commenced in the late 20s and continued at a rate of 0.4% per year. The cumulative premenopausal loss from the femur at 9% was comparable to that in the spine. It is concluded that significant amounts of trabecular bone are lost from both the spine and femoral neck before the menopause. The implications of these findings for the prevention of osteoporosis are discussed. PMID- 2331426 TI - No effect of APD (amino hydroxypropylidene bisphosphonate) on hypercalcemia in patients with renal osteodystrophy. AB - Hypercalcemia, due to autonomous functioning of the parathyroids following long standing secondary hyperparathyroidism, is a well known complication in patients with renal osteodystrophy, which can on most cases be treated by parathyroidectomy only. While patients with renal osteodystrophy react favorably to supplementation of active vitamin D metabolites to prevent or reverse renal osteodystrophy, the use of these drugs is bound to result in greater hypercalcemia in those patients who are already hypercalcemic. The question rose if the bisphosphonate amino hydroxypropylidene bisphosphonate (APD) would decrease plasma calcium concentration sufficiently in order to create room for the use of vitamin D to cure the osteomalacia component of the osteodystrophy and simultaneously block the excessive bone resorption. Therefore, five patients with renal osteodystrophy and hypercalcemia were treated for up to 9 months with APD. Three of them, who were on chronic hemodialysis, received 15 mg APD i.v. 3 times a week, the 2 other patients with severe renal failure received 200 mg APD orally. Ionized calcium in plasma did not decrease. Histological investigation of bone samples, obtained before and after therapy, showed an increase of fibrous tissue and a remarkable increase in the number of osteoclasts or osteoclast-like cells not only along the bone-margin, but mainly within the bone-marrow. We conclude that in patients with renal failure with hypercalcemia, APD in the doses used had no effect on plasma calcium level, but caused a striking change in bone histology. Although the consequences of these findings are not yet clear, they do not seem to indicate improvement of bone structure. PMID- 2331427 TI - Mechanical properties of bone from iliac crest and relationship to L5 vertebral bone. AB - Apparent density, yield stress and yield energy were measured in transiliac cores of trabecular bone from iliac crest and craniocaudal cores of L5 vertebra from 26 cadavers. In the iliac crest, bone from the anterior superior spine region had significantly greater apparent density and had greater yield energy than bone from the center of the crest. Yield stress was greater at the anterior superior spine than either the center or at the posterior spine. Lumbar vertebral bone was uniform in its characteristics. Apparent density was the property showing the best correlation between iliac crest and L5 (r = 0.79), while yield energy was less well associated (r = 0.67). In L5, mechanical properties decline more rapidly with age than apparent density. Between the ages of 25 and 75 years the rate of fall of yield stress was twice and yield energy 2.6 times compared with the rate of fall of apparent density. Iliac crest behaved similarly. Yield stress in iliac crest paired for density in subjects less than 40 years and greater than 60 years was 40.7% lower in the older subjects (p = 0.03), suggesting a specific mechanical defect in old age. The yield stress advantage accruing to orientated lumbar bone was more marked at lower values of yield stress in the iliac crest when cores from the same cadaver were matched for apparent density. Mechanical properties of iliac crest bone are very dependent upon site and at no one site in the iliac crest do the physical properties satisfactorily predict those in the lumbar spine. PMID- 2331428 TI - Effect of calcitonin administration on young pig trabecular bone remodeling. AB - Ten-week-old pigs were treated with 4 different treatment schedules of porcine calcitonin for 2 months. Groups C1 and C4 received continuous treatment: C1 had daily IM injections (4 IU/kg/BW (body weight) each injection), and C4 was infused with a minipump implanted subcutaneously delivering 4 IU/kg/BW/day. Groups C2 and C3 received intermittent calcitonin treatment (each injection 4 IU/kg/BW): C2 was given 1 out of every four days, C3 was injected 5 consecutive days out of 20 days. The total dosage received in C1 versus C4 and C2 versus C3 were the same. Results were evaluated by histomorphometry after double tetracycline labeling on iliac trabecular bone. Resorption surfaces were decreased in groups C2, C3 and C4, but bone volume, osteoclast surfaces, and interstitial bone thickness were not modified in any group receiving calcitonin. Osteoblast and mineralizing surfaces were increased in group C2, C3 and C4. Plasma 1,25-dihydroxyvitamin D concentration and bone formation rate were increased in groups C2 and C4. Plasma immunoreactive parathyroid hormone levels and parathyroid weights were not increased in any treated groups. In conclusion, 2-month calcitonin treatment did not decrease the amount of bone resorbed in growing pigs. Continuous calcitonin infusion and intermittent calcitonin administration induced an increase in the extent of active bone formation which might be in part dependent on an increased production of 1,25 dihydroxyvitamin D. PMID- 2331429 TI - The quantitative study of the orientation of collagen in compact bone slices. AB - We describe and validate a simple method for the study of the proportion of collagen fibers (and apatite crystals) in a bone slice parallel with the plane of section. Viewed between crossed circular polarizers, all bone areas with collagen lying more nearly in the plane of section (i.e., transverse [TS] collagen) appear bright whatever its direction in this plane; longitudinal [LS] collagen appears dark, but not as dark as the background. The degree of brightness increases with section thickness, which must therefore be standardized--we chose 100 microns plane parallel sections. We transferred the circularly polarized light [CPL] image via a CCD TV camera to an image analyzing computer. Color-coded maps of the CPL image were used to compare regions within and between sections. The new analytical procedure makes more detailed studies of the fine-structural orientation in compact bone possible, but does this have any significance? To answer this question, a bone in which the in vivo strain pattern had been clearly documented was chosen for particular study. Transverse mid-diaphyseal sections of the equine radius showed a distribution of CPL bright areas which correlated closely with previously reported strain patterns. PMID- 2331430 TI - The effects of uremia and dietary phosphorus on the bone of rats. AB - In order to evaluate the effects of uremia and low levels of dietary phosphorus on bone, male Sprague-Dawley rats weighing 320 +/- 20 g (12 weeks old) were subjected to either a two-step, subtotal nephrectomy or sham-operation (SO), and then fed a custom diet with either normal calcium (0.5%) and normal phosphorus (0.3%) (NCNP), or normal calcium and low phosphorus (0.03%). When compared to the NCNP SO group after seven days, only uremic rats fed low phosphorus diets developed osteomalacia characterized by an increase in the osteoid thickness, surface and volume, a prolonged osteoid maturation time, and a decreased bone formation rate. No other groups developed these changes. This osteomalacia was also associated with hypophosphatemia, a reduced serum PTH and an elevation in the serum 1,25(OH)2D3. It was concluded that while neither this degree of uremia nor the low phosphorus diets alone had any significant effect, the combination of uremia and low dietary phosphorus resulted in the initiation of osteomalacia. This animal model should prove useful in investigations dealing with the influence of uremia on the mineralization process. PMID- 2331431 TI - Effects of ethanol and acetaldehyde on collagen synthesis, prostaglandin release and resorption of fetal rat bone in organ culture. AB - We tested the effect of ethanol and its metabolite, acetaldehyde, on bone formation as measured by [3H]proline incorporation into collagenase digestible protein (CDP) and noncollagen protein (NCP), and on DNA synthesis as measured by [3H]thymidine (TdR) incorporation in fetal rat calvaria. We also determined the effects of ethanol and acetaldehyde on prostaglandin E2 (PGE2) release from calvaria and on bone resorption as measured by 45Ca release from fetal rat long bones. Bones were cultured in multiwell plastic dishes (open system) or in stoppered Erlenmeyer flasks (closed system) for 24 to 96 h. In the open system, 1% ethanol (v/v; 172 mM) resulted in a 31% decrease in TdR incorporation at 24 h with no effect on CDP and NCP. At 0.1% (17.2 mM), ethanol increased TdR by 22%, CDP by 73% and NCP by 67% at 24 h, but these effects were not sustained at 96 h. At 24 h, 1% and 0.3% ethanol decreased PGE2 release by 88% and 75% respectively. This effect was sustained for 96 h only at the higher concentration. In the closed system, 0.1% ethanol increased TdR incorporation by 38% at 24 h. However, there was no effect on the labeling of CDP or NCP. Because its boiling point is 21 degrees C, acetaldehyde could only be tested in the closed system. Acetaldehyde markedly inhibited bone metabolism. At 24 h, 0.003% (0.54 mM) to 0.01% (1.79 mM) acetaldehyde caused a dose-related inhibition of TdR incorporation from 23 to 45%. At 0.01% and 0.03% acetaldehyde inhibited proline incorporation into CDP by 48% and 94% and NCP by 40% and 74% respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331432 TI - Retinoic acid and 1,25-dihydroxyvitamin D3 stimulate osteoclast formation by different mechanisms. AB - The effects of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3 on osteoclast formation were examined in intact fetal long bones of different ages/developmental stages maintained in organ culture using a chemically defined medium with or without the presence of serum. Besides stimulating bone resorption, RA and 1,25-(OH)2D3 increased the number of osteoclasts in 19-day-old fetal rat tibiae. Likewise, these bone-resorbing agents induced and stimulated osteoclast formation in 19- and 18-day-old metatarsal bones which were osteoclast free at the beginning of the culture. The response to 1,25-(OH)2D3 was greatly enhanced by 10% fetal bovine serum (FBS) irrespective of the developmental stage of the long bone. The response to RA was not. Light microscopic autoradiography after labeling of the cultures with tritiated thymidine showed that both RA and 1,25-(OH)2D3 induced osteoclast differentiation from proliferating and postmitotic precursors. However, neither agent was able to stimulate proliferation of osteoclast progenitor cells in the older bones (19 days). Studies on the formation of osteoclast-like (tartrate-resistant acid phosphatase positive) cells in bone marrow cultures indicated that FBS was a potent inducer of osteoclast-like cell formation. In the presence of FBS, 1,25-(OH)2D3 significantly stimulated this response, but RA did not. The results demonstrate that although both RA and 1,25-(OH)2D3 stimulate osteoclast formation from proliferating and postmitotic precursors in long bones in vitro, they do so by different mechanisms. PMID- 2331433 TI - Simultaneous assessment of bone resorption and formation in cultures of 22-day fetal rat parietal bones: effects of parathyroid hormone and prostaglandin E2. AB - We have developed a method that allows us to measure bone resorption and formation simultaneously in the parietal bones from 22-day fetal rat calvaria. Parietal bones labeled with 45Ca, by injection of the mother, were cultured for 72 h with parathyroid hormone (PTH, bovine 1-34, 1.56 nM) or prostaglandin E2 (PGE2, 100 nM), in the presence or absence of indomethacin (Indo, 1 microM) or corticosterone (Cort, 1 microM). Two hours prior to the end of the culture, the bones were pulsed with [3H]-proline or [3H]-thymidine. Resorption was assessed as the percent of 45Ca released into the medium. Incorporation of [3H]-proline into collagenase digestible protein (CDP) and of [3H]-thymidine into DNA (TDR) were measured to assess collagen and DNA synthesis, respectively. Basal %45Ca release was 16 +/- 1% and was significantly decreased by Indo and Cort. Cort decreased TDR and CDP while Indo did not. PTH and PGE2 significantly increased %45Ca release, and this was not blocked by Indo. However, in the presence of Cort, only PTH increased %45Ca release while PGE2 did not. PGE2 increased TDR under all culture conditions while PTH increased TDR only in the presence of Cort. While PTH and PGE2 had the same effects on bone resorption, they had different effects on CDP. PGE2 increased CDP in the presence of Indo or Cort but PTH did not. Thus, this model allows us to study bone resorption, collagen synthesis, and DNA synthesis simultaneously. We have also shown that PTH and PGE2 differ in their sensitivity to inhibition of resorption by Cort and in their effects on bone formation. PMID- 2331434 TI - Relation of axial bone mass to habitual calcium intake and to cortical bone loss in healthy early postmenopausal women. AB - A group of 60 healthy early postmenopausal women participating in an ongoing study on the effect of habitual calcium intake on the rate of cortical bone loss at the radius, were subjected to additional skeletal measurements at the lumbar spine and femoral neck. The women were between 58 and 64 years of age, and 3 to 10 years postmenopausal. No correlations were found between habitual calcium intake (range 560 to 2580 mg/day) and either bone mineral content of the radius, the lumbar spine and the femoral neck, or spine deformity index. Body mass index was found to be positively correlated with bone mass indices of the radius (decrease of BMD and BMD) and femoral neck (BMC), but not with of the lumbar spine (BMC, BMD and SDI), even after adjustments had been made for confounding factors. Although the rate of cortical bone loss at the radius correlated significantly with bone mineral content of lumbar spine and femoral neck, the error in predicting bone mass of the lumbar spine or the femoral neck from longitudinal measurements of cortical bone at the radius was high. The rate of cortical bone loss did not correlate with the spine deformity index. We conclude that in healthy women in early menopause, the bone mineral content of both the appendicular and the axial skeleton are not influenced by habitual calcium intake. A higher body mass index has a protective effect on the appendicular skeleton but appears to be less protective to the axial skeleton. Longitudinal measurements of cortical bone mass are of limited value to predict bone density of the appendicular and axial skeleton. PMID- 2331435 TI - Fatty acid control of growth of human cervical and endometrial cancer cells. AB - Stearic acid and iodo-stearic and inhibited cell growth in a cervical cancer cell line (HOG-1) in a dose-related manner, with a half maximal effect at 50 microM stearic acid. Addition of oleic acid abrogated the effect of stearic acid. EGF stimulated DNA synthesis and growth of HOG-1 cells was inhibited in the presence of stearic acid without any apparent effect on EGF receptor number or affinity. PMID- 2331436 TI - A bispecific monoclonal antibody against methotrexate and a human tumour associated antigen augments cytotoxicity of methotrexate-carrier conjugate. AB - A bispecific monoclonal antibody, reactive with methotrexate (MTX) and a tumour associated antigen (gp72) has been produced by fusing spleen cells from MTX immunised mice with 791T/36/3 (anti-gp72) hybridoma. The hybrid antibody was purified from anti-MTX and anti-gp72 antibodies present in the hybridoma culture supernatant by combinations of affinity chromatography on a MTX-agarose immunoabsorbent and stepwise acid elution from Sepharose-Protein A. A particular feature of the present antibody is that it reacts with conjugated MTX; this would allow in vivo targeting of conjugates, increasing many fold the number of molecules of drug carried or localising to pre-targeted antibody. Dual binding between tumour cell surface antigen and MTX was demonstrated by the ability of the hybrid antibody to bridge between tumour cells and MTX as MTX-HSA conjugate, reaction here being detected by flow cytofluorimetry. Purified hybrid antibody specifically enhanced the in vitro cytotoxicity of MTX-HSA for gp72 positive tumour cells. PMID- 2331437 TI - Metabolic effects of tumour necrosis factor alpha in NMRI mice. AB - Following a single injection of 7.5 x 10(7) U kg-1 of human recombinant tumour necrosis factor-alpha (TNF-alpha) to female NMRI mice, marked hypoglycaemia was observed within a 2 h period, accompanied by a severe depletion of liver glycogen and a drop in rectal body temperature when compared with pair-fed controls. There was no alteration in plasma alanine, lactate or pyruvate values, but an elevation of acetoacetate and 3-hydroxybutyrate when compared with pair-fed controls. Production of 14CO2 from U-14C-glucose was reduced in TNF-alpha treated animals, while production of 14CO2 from U-14C-palmitate was not significantly different from controls, suggesting that the glucose was not being used to provide an increased metabolic rate. Glucose utilisation by different tissues was investigated by the 2-deoxyglucose tracer method. This showed that 2 h following TNF-alpha infusion glucose utilisation was increased in colon, liver, kidney and spleen by 500, 350, 36 and 25% respectively. However, when calculated on a whole animal basis the major contributor to the increased glucose consumption was the liver. Plasma levels of both FFA and triglycerides were also elevated in TNF alpha treated animals, suggesting that increased consumption of glucose by the liver may be utilised for lipogenesis. The rate of conversion of glucose into lipids in the liver was more than doubled 2 h after TNF-alpha administration with a concomitant rise in plasma and adipose tissue. These results suggest that administration of TNF-alpha produces a severe hypoglycaemia in order to serve an increased lipogenesis in liver and adipose tissue, which appears to be independent of the anorectic effect. PMID- 2331438 TI - An immunoradiometric assay of tumour-antigen 4 (TA-4): a comparison with conventional radioimmunoassay. AB - The serum level of tumour-antigen 4 (TA-4) was measured in 181 patients with squamous cell carcinoma (SCC) of various organs (71 lung, 24 uterus, 16 oesophagus, 64 head and neck and six skin), 34 patients with other types of lung cancer and 35 patients with benign diseases. To compare the results with those obtained by the conventional competitive radioimmunoassay (RIA) using a polyclonal antibody, a new immunoradiometric assay (IRMA) method was used which has recently been developed using two monoclonal antibodies raised to different epitopes of TA-4. Both methods provided essentially the same results: the serum TA-4 levels were high in patients with SCC of various organs when compared with those of healthy controls and patients with other types of lung cancer or benign diseases. However, the positive ratios assessed as the percentage of patients with elevated serum TA-4 levels were higher with the IRMA method than with the RIA method in SCC of all organs, as much as 2-3 times higher in SCC of the larynx, tongue and pharynx. In contrast, in patients with benign diseases or other types of lung cancer, there was no difference in the positive ratios between the two methods. This was largely due to the improvement in sensitivity and accuracy of assay with the new method, which resulted in a decrease in the normal value in healthy controls. It was concluded that with the new IRMA method using monoclonal antibodies, the diagnostic detectability of serum TA-4 is enhanced in SCC of all organs. PMID- 2331439 TI - NAD(P)H nitroblue tetrazolium reductase levels in apparently normoxic tissues: a histochemical study correlating enzyme activity with binding of radiolabelled misonidazole. AB - Hack and Helmy's method for the histochemical identification of NAD(P)H nitroblue tetrazolium reductase activity was employed to pinpoint reductase activity in certain cells in the mouse. High activity was observed in the following: lower airway epithelium, liver (centrilobular zone), eyelid (meibomian and sebaceous glands), vulval gland and parotid gland (striated cells of intralobular ducts). All of these cells had previously been identified as sites of binding of the reactive metabolites formed from the enzymic reduction of misonidazole (MISO) (Cobb et al., 1989). It had previously been thought that MISO binding would only take place in significant amounts in hypoxic tissues (tumour and possibly liver) since in normoxic tissues oxygen should reverse the initial one electron enzymic reduction, thus preventing progressive reduction to reactive species. We suggest that the very high levels of reductase in the above listed, probably normoxic, tissues contribute significantly to the accumulation of bound reactive MISO metabolite(s). PMID- 2331440 TI - Haemoglobin adducts formed by aromatic amines in smokers: sources of inter individual variability. AB - In a previous study we found that aromatic amines, particularly 4-aminobiphenyl, formed haemoglobin adducts at higher concentrations in the blood of smokers compared to non-smokers. We re-analyse here data on haemoglobin adducts of 14 aromatic amines in order to ascertain if the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. For this purpose we computed residuals from analysis of variance in order to adjust for individual smoking habits (type and amount of tobacco). Residuals were correlated within two clearly distinct groups: one formed by binuclear compounds (4-aminobiphenyl, 3-aminobiphenyl and 2 naphthylamine) and the other formed by all other (i.e. mononuclear) compounds. Within each group, highly statistically significant correlation coefficients were found, whereas compounds belonging to one group were not correlated to compounds in the other group. These results can be interpreted as a suggestion that two different metabolic pathways exist, one for binuclear and one for mononuclear arylamines, and that inter-individual differences in such pathways can explain part of inter-individual variability in adduct levels. This interpretation is consistent with recent animal experiments suggesting that there are different enzyme systems for the two classes of compounds. PMID- 2331441 TI - Cellular pharmacology of 4'-iodo-4'-deoxydoxorubicin. AB - We have studied the growth inhibition, DNA synthesis inhibition and cell incorporation of the new anthracycline 4'-iodo-4'-deoxydoxorubicin (4' iododoxorubicin) and of its 13-dihydroderivative in a model of doxorubicin sensitive and -resistant rat C6 glioblastoma cells; results were compared to those obtained with doxorubicin and doxorubicinol in the same model. 4' Iododoxorubicin was 7.5 times more potent than doxorubicin on the wild cell line and 45 times on the doxorubicin-resistant line, indicating that cross-resistance was only partial between the two drugs. Whereas doxorubicinol presented only a very faint cytotoxic activity, 4'-iododoxorubicinol retained the same activity as the parent drug against sensitive cells and a lower activity against resistant cells. DNA synthesis inhibition occurred for much higher doses than growth inhibition in the sensitive cells, but for similar doses in resistant cells. In both cell lines, 4'-iododoxorubicin and its metabolite were incorporated to a higher extent than doxorubicin and doxorubicinol respectively. Incorporation of metabolites was always lower than that of their parent compound. We have studied the metabolism of doxorubicin and 4'-iododoxorubicin by sensitive and resistant cells; only traces (less than 5%) of metabolites were identified in the cells as well as in the culture medium. A new cell line was selected for resistance in the presence of low amounts of 4'-iododoxorubicin. It presented a 6-fold resistance to 4'-iododoxorubicin and an 85-fold resistance to doxorubicin. Doxorubicin incorporation was markedly reduced in this cell line while 4'-iododoxorubicin was incorporated to the same extent as in the sensitive line. Measurements of drug efflux were performed in the three cell lines. No significant difference was exhibited between the efflux of doxorubicin and that of 4'-iododoxorubicin in each cell line; these effluxes were very rapid in the doxorubicin-selected resistant line, slow in the wild line and intermediate in the 4'-iododoxorubicin selected line. PMID- 2331442 TI - Enhancement of the radiosensitivity of two human tumour cell lines by hexamethylene bisacetamide. AB - The effect of the maturation-inducing polar solvent, hexamethylene bisacetamide (HMBA), on the radiosensitivity of two human tumour cell lines (clone A, a colon carcinoma; and EJ, a bladder carcinoma) was investigated. Exposure of clone A or EJ cells to HMBA resulted in a concentration-dependent increase in doubling time, a decreased plating efficiency and changes in cell morphology, which are consistent with the formation of a better-differentiated phenotype. Growth of clone A cells in 2 or 3 mM HMBA, followed by irradiation and plating into HMBA free medium, resulted in a significant enhancement in radiosensitivity, as determined by colony-forming ability. A similar increase in radiosensitivity was detected for EJ cells; however, for these cells a concentration of 7 mM HMBA was required. The increased radiosensitivity caused by HMBA was observed primarily in the low-dose, shoulder region of the gamma-ray cell survival curves for both cell lines, which is reflected by an increase in the alpha component of the survival curve with essentially no effect on beta. These data indicate that HMBA can radiosensitise human tumour cells at concentrations and for exposure periods that can be achieved in the clinic. PMID- 2331443 TI - Stomach cancer and migration within England and Wales. AB - Rates of stomach cancer vary from place to place within England and Wales. To determine whether this reflects influences acting earlier or later in life, we have analysed mortality from the disease by county of birth and county of death. Among 749,035 men and women who died during 1969-72 in a different county from that in which they were born, proportional mortality from stomach cancer was more closely related to county of birth than of death. This association with place of birth was found in migrants both out of and into high-risk areas. We conclude that studies seeking to explain local differences in the incidence of stomach cancer within England and Wales should focus on the environment of patients in their youth. PMID- 2331444 TI - Poor housing in childhood and high rates of stomach cancer in England and Wales. AB - In a search for aetiological processes which might explain the association of stomach cancer with poverty, we have related mortality from the disease in the local authority areas of England and Wales during 1968-78 to indices of living standards derived from the 1971, 1951 and 1931 censuses. We have also analysed recently released data from a national survey of overcrowding carried out in 1936. Geographical differences in stomach cancer were most closely related to occupationally derived indices of socio-economic structure from the 1971 census, and to measures of domestic crowding from the 1931 census and 1936 survey. Unlike other indices of poor living standards, levels of past domestic crowding in north west Wales were consistent with its previously unexplained high death rates from stomach cancer. We conclude that overcrowding in the home during childhood may be a major determinant of stomach cancer, and might act by promoting the transmission of causative organisms. PMID- 2331445 TI - Time trends in the outcome of lung cancer management: a study of 9,090 cases diagnosed in the Mersey Region, 1974-86. AB - The purpose of this paper is to describe temporal trends in the treatment of lung cancer in the Merseyside Region of England over the years 1974-86. A detailed analysis of 9,090 cases of histologically confirmed tumours showed that age at diagnosis and histological type were important prognostic factors, with the 5 year survival of adenocarcinoma, squamous carcinoma, undifferentiated carcinoma and small cell carcinoma after treatment being 22.5%, 18.5%, 10% and 3.5% respectively. An analysis of 741 cases of small cell carcinoma given chemotherapy over the same period showed progressive improvement in 2 year survival from 2.5 to 7.5% (P less than 0.001) and this was shown to be closely associated with the increasing use of intravenous combination chemotherapy. The survival of patients who underwent surgical resection in the three periods 1974-77, 1978-81 and 1982 86 showed a continuous improvement in median survival from 13 to 30 months (P less than 0.001). Overall survival curves of all treated cases showed a significant improvement in median survival from 8 to 10 months and 5 year survival from 12.5 to 17.5% (P = 0.001). With improved staging assessment, the value of surgical resection of all histological types is emphasised, and in the case of the small cell subtype, the increasing use of combination chemotherapy would appear to have paralleled an increase in median and 2 year survival. These data support the argument that with appropriate case selection, there is a survival benefit associated with active treatment for lung cancer. PMID- 2331446 TI - Transcripts for transforming growth factors in human breast cancer: clinical correlates. AB - The levels of mRNA for transforming growth factors (TGF alpha and beta) and the epidermal growth factor receptor (EGFR) were determined in 69 human breast carcinomas and 20 biopsies of non-neoplastic breast tissue by dot blot hybridisation analysis. TGF alpha mRNA was detected in 42% of cancers and 44% of non-neoplastic breast tissue at low levels. TGF beta mRNA was found in all breast cancers and non-neoplastic breast tissues, but the levels of TGF beta mRNA were found to be higher in breast cancers (P = 0.01). EGFR mRNA was detected in 55% of breast cancers and in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inversely related to oestrogen receptor (ER) status (P = 0.0001). Coexpression of TGF alpha and EGFR was observed in 28% of the carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). No significant relationship was found between histological grade, tumour cellularity or tumour desmoplasia and expression of either the TGFs or of EGFR mRNA. High levels of TGF beta were, however, associated with the absence of lymph node metastases at presentation (P = 0.05). Levels of TGF alpha and beta and EGFR mRNA were analysed in relationship to the relapse-free and overall survival of patients with breast cancer, but none was found to predict significantly the outcome in these patients. Longer clinical follow-up and larger numbers of patients are required to determine whether TGFs will prove a useful marker for prognosis in breast cancer patients. PMID- 2331447 TI - Recombinant interleukin-2 (rIL-2) with flavone acetic acid (FAA) in advanced malignant melanoma: a phase II study. AB - Recombinant interleukin 2 (rIL-2) and flavone acetic acid (FAA) were used to treat 34 patients with progressing metastatic melanoma. Five patients had solely non-visceral disease and the median number of organ sites involved was two. Five doses of rIL-2 were given, the first dose intrasplenically via a femoral artery catheter with a further dose 4 h later i.v. and the other doses i.v. on alternate days. The rIL-2 dose was 11 x 10(6) Cetus units m-2; the day before rIL-2, FAA (4.8 G m-2) was given as a 6 h i.v. infusion, in order to enhance further killer cell activity. A total of three courses at 21-day intervals was planned and 74 courses in all were given. Despite the high dose of rIL-2 and the potential overlapping toxicity affecting blood pressure with the addition of FAA, side effects were generally mild. There were only five episodes of grade 4 toxicity: one of ventricular tachycardia and four other episodes of transient biochemical or haematological disturbance. Grade 3 hypotension or hypertension occurred on 22 courses but again was transient. No patient required intensive care facilities. Five patients had tumour response, one being complete. Responses occurred in pulmonary and hepatic metastases, but mainly in non-visceral sites. Eleven patients remain alive at 6-17 months and in five there is no relapse or progression of disease. Despite the impressive results in animal tumour models, the addition of FAA to rIL-2 in the present study has not markedly improved results over rIL-2 alone. PMID- 2331448 TI - Nucleolar organiser regions in myeloma and benign paraproteinaemia. PMID- 2331449 TI - Relationships among semantic differential change measures of splitting, self fragmentation and object relations in borderline psychopathology. AB - This pilot study investigated associations among change measures in a sample of borderline patients participating in an intensive, group-oriented day treatment programme. Change scores over a four-month period were calculated from measures of splitting dynamics, self-perceptions, and experiences of interpersonal relationships. Correlations provided partial empirical support for the hypothesized associations among these variables. Findings suggested that as splitting decreased, patients developed a more benevolent, and more anaclitic, view of self-in-the-world. PMID- 2331450 TI - Mental illness and religious change. AB - Over the last 20 years there has been a revival of interest in orthodox Judaism in Israel. In an area of Jerusalem with a large concentration of academies of study for 'baalei teshuva' (those who have undergone change to orthodox Judaism), it was noted that 12.6 per cent of referrals to the community mental health centre were newly religious. These referrals tended to have schizophrenia or severe personality disorders and were less likely than other referrals to have anxiety, depressive or adjustment disorders. Most of the newly religious referrals had psychiatric problems prior to becoming religious. Subsequent to religious change, many married and started a family before their psychiatric referral. The link between religious change and mental illness is explored. PMID- 2331451 TI - A comparison of the affective well-being of young and middle-aged unemployed men matched for length of unemployment. AB - A sample of young unemployed men (mean age: 21.7 years) was compared with a sample of middle-aged unemployed men (mean age: 47.8 years) on a range of psychological and demographic/background variables. The groups were fortuitously matched for length of unemployment, with the average duration of current unemployment being 20.0 months for the young group and 17.9 months for the middle aged group. The middle-aged group displayed poorer mental health, less life satisfaction and greater work involvement than the young group but the groups did not differ in self-esteem. For the young group the best predictor of well-being was perceived adequacy of social support and for the middle-aged group the best predictor was participation in leisure activities involving other people. It was concluded that the poorer mental health displayed by middle-aged unemployed men is not explained by the fact that they have, in general, been unemployed for longer than their young counterparts. In both groups, the best predictor of affective well-being was a measure (albeit a different measure) of social support. These conclusions can only be regarded as tentative, however, because of the small sample sizes. Implications of these findings for community support programmes for both young and middle-aged unemployed groups are discussed. PMID- 2331452 TI - The effect of a pre-appointment questionnaire on clinical psychologist attendance rates. AB - A 12-page, psychodynamically-formulated questionnaire is sent routinely to people referred to a clinical psychology service. This study examines its effect on attendance rates at initial appointments. A group of patients who were sent the questionnaire was compared to two control groups. There were indications that those who were sent the questionnaire were more likely than controls to attend. The result failed to reach statistical significance at the 5 per cent level, but, using a more conservative criterion, those who were sent the questionnaire were significantly more likely than controls to make contact--either by attending or actively cancelling their appointment--rather than simply failing to turn up. PMID- 2331453 TI - Troubled parents: vulnerability and stress in childhood cancer. AB - The psychosocial stresses of having a child with cancer were examined in a group of 18 parents using standard psychiatric measurement scales and a lengthy semi structured interview. Findings confirmed that staff/parent communication is difficult in a large institution but can be facilitated by staff who are aware of the difficulty. Two kinds of psychopathology were demonstrated in the parents. Thirteen of the 18 suffered symptoms of anxiety outside the normal range: of these 13, six had moderate or severe symptoms which warranted further attention. A group of six parents showed marked communication difficulty with staff, friends and their own spouses. The latter may represent a pre-existing personality trait but one which makes the experience of having a child with cancer even more distressing. PMID- 2331454 TI - A comparison between women seeking self-help and psychiatric treatment in anorexia nervosa and bulimia. AB - Thirty new members of a branch of Anorexic Aid were interviewed to determine their characteristics and compared with women seeking psychiatric treatment for anorexia nervosa and normal-weight bulimia. It was expected that the two samples would be similar and that the women in the self-help group would have also had professional treatment. Over half (53 per cent, 16) of the Anorexic Aid sample were anorectic, 40 per cent (12) were normal-weight bulimics and 7 per cent (2) could not be classified and were excluded. Demographic characteristics were similar, with both samples being mainly British, single and from social classes I III, but the Anorexic Aid sample was significantly older. Clinical features were also similar, although there was a trend towards the Anorexic Aid anorectics being less severely ill at presentation. Nearly 90 per cent (25) of the Anorexic Aid sample had had professional treatment. The hypotheses are partially confirmed. Reasons for the differences in age and severity are discussed. PMID- 2331455 TI - Psychological aspects of male infertility. AB - The aim of this research was to study the effect of suspected infertility on psychological functioning, comparing men who suspect that they are infertile (N = 107) with men who have no such suspicion (N = 30). Infertile men had lower self esteem, higher anxiety and showed more somatic symptoms than fertile men. The effects of moderating variables on the psychological functioning of the subfertile men were analysed. The findings were that causality of infertility, feelings of hopelessness and global attribution were related to sexual inadequacy. Depression was uniquely related to stress of infertility and global attribution. Global attribution, though predictive of psychological consequences, was not affected by the objective variables of infertility. PMID- 2331456 TI - Type A behaviour and health locus of control: another view on Perloff et al. (1988) AB - Perloff, Yarnold & Feltzer (1988) recently reported in this journal data suggesting that Type A undergraduates are more internal in their health locus of control than Type Bs, and suggest this may have implications for their health behaviour and self-care. Data from a non-college sample of 104 Type A and B adults were examined using the same measures, but could not replicate the findings of Perloff et al. Several reasons for the failure to replicate are discussed, including statistical power, clinical meaningfulness, and current theory on the Type A-health behaviour relationship. PMID- 2331457 TI - The standardization of terminology of lower urinary tract function. PMID- 2331458 TI - Methane monooxygenase catalyzed oxygenation of 1,1-dimethylcyclopropane. Evidence for radical and carbocationic intermediates. AB - Methane monooxygenase catalyzes the oxygenation of 1,1-dimethylcyclopropane in the presence of O2 and NADH to (1-methylcyclopropyl)methanol (81%), 3-methyl-3 buten-1-ol (6%), and 1-methyl-cyclobutanol (13%). Oxygenation by 18O2 using the purified enzyme proceeds with incorporation of 18O into the products. Inasmuch as methane monooxygenase catalyzes the insertion of O from O2 into a carbon-hydrogen bond of alkanes, (1-methylcyclopropyl)methanol appears to be a conventional oxygenation product. 3-Methyl-3-buten-1-ol is a rearrangement product that can be rationalized on the basis that enzymatic oxygenation of 1,1-dimethylcyclopropane proceeds via the (1-methylcyclopropyl)carbinyl radical, which is expected to undergo rearrangement with ring opening to the homoallylic 3-methyl-3-buten-1-yl radical in competition with conventional oxygenation. Oxygenation of the latter radical gives 3-methyl-3-buten-1-ol. 1-Methylcyclobutanol is a ring-expansion product, whose formation is best explained on the basis that the 1 methylcyclobutyl tertiary carbocation is an oxygenation intermediate. This cation would result from rearrangements of carbocations derived by one-electron oxidation of either radical intermediate. The fact that both 3-methyl-3-buten-1 ol and 1-methylcyclobutanol are produced suggests that the oxygenation mechanism involves both radical and carbocationic intermediates. Radicals and carbocations can both be intermediates if they are connected by an electron-transfer step. A reasonable reaction sequence is one in which the cofactor (mu-oxo)diiron reacts with O2 and two electrons to generate a hydrogen atom abstracting species and an oxidizing agent. The hydrogen-abstracting species might be the enzymic radical or another species generated by the iron complex and O2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331459 TI - 1H NMR studies of tris(phenanthroline) metal complexes bound to oligonucleotides: characterization of binding modes. AB - The binding of Ru(phen)3(2+), Rh(phen)3(3+), and Co(phen)3(3+) to the oligonucleotides d(GTGCAC)2 and 5'-pd(CGCGCG)2 has been examined by 1H NMR spectroscopy as a function of temperature, concentration, and chirality of the metal complex. The duplex oligonucleotides act as chiral shift reagents for the metal complexes; phenanthroline protons associated with each enantiomer are resolved upon binding to the oligomer. The spectral titrations, consistent with photophysical studies, indicate that the complexes bind to the oligomer through two modes: one assigned as intercalation favoring the delta-isomer, and the other assigned as the surface-bound interaction favoring the lambda-isomer. The ligand protons are perturbed in a manner that implies sensitivity of particular protons to binding mode; specifically, the H4,7 protons appear to be altered most for the lambda-enantiomer while the H5,6 protons are perturbed more for the delta enantiomer. The NMR chemical shift variations appear particularly sensitive to this surface-bound interaction, which, on the basis of a comparison of binding and photophysical parameters for Ru(phen)3(2+), appears more prominant in binding to oligonucleotides than that to polynucleotides. With respect to oligonucleotide proton shifts, the adenine H2 proton, positioned in the minor groove of the helix, shows the largest upfield shifts with metal binding, and more dramatically with lambda-isomers. The major groove thymine methyl protons (TMe) shift downfield to a lesser extent, and more so for delta-isomers. The different binding modes also differ with respect to their dynamics of association; the longitudinal relaxation rates of delta- and lambda-4,7 phenanthroline protons of Rh(phen)3(3+) are 0.88 and 1.14 s, respectively, in the presence of d(GTGCAC)2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331460 TI - 1H NMR studies of tris(phenanthroline) metal complexes bound to oligonucleotides: structural characterizations via selective paramagnetic relaxation. AB - The selective paramagnetic relaxation of oligonucleotide protons of d(GTGCAC)2 by delta- and lambda-Ni(phen)3(3+) and delta- and lambda-Cr(phen)3(3+) has been examined to obtain some structural insight into the noncovalent binding of tris(phenanthroline) metal complexes to DNA. The experiments demonstrate that the relative rate of relaxation of different oligonucleotide protons by the paramagnetic metal complex varies with the chirality of the metal complex and, to a lesser extent, the metal charge. The proton most efficiently relaxed in all cases is the adenosine AH2, which is situated in the minor groove of the oligonucleotide helix. For both lambda-Ni(phen)3(2+) and lambda-Cr(phen)3(3+), the order of relaxation rates varies as AH2 much greater than AH8 greater than G3H8 = TMe = C4H5. For delta-Ni(phen)3(2+) it varies as AH2 greater than G3H8 greater than AH8 greater than TMe = C4H5 and for delta-Cr(phen)3(3+) as AH2 greater than TMe = G3H8 = AH8 greater than C4H5. Distances between the metal center and oligonucleotide protons were calculated on the basis of the relaxation data, and these distances were used to generate a set of models to describe the interactions of the rigid metal complex with the helix. For lambda-isomers, the data are consistent with a predominant surface-bound association in the minor groove of the DNA helix. The results of delta-isomers correlate better with models that incorporate also a major groove intercalative mode. Despite the absence of hydrogen-bonding groups in the metal complex, the surface-bound model of the phenanthroline complex in the minor groove of DNA resembles the noncovalent association seen with other DNA groove binding molecules. PMID- 2331462 TI - 500-MHz proton NMR evidence for two solution structures of the common arm base paired segment of wheat germ 5S ribosomal RNA. AB - The base-pair protons of the common arm duplex fragment of wheat germ (Triticum aestivum) ribosomal 5S RNA have been identified and assigned by means of 500-MHz proton NMR spectroscopy. The two previously reported extra base pairs within the fragment [Li et al. (1987) Biochemistry 26, 1578-1585] are now explained by the presence of two distinct solution structures of the common arm fragment (and its corresponding base-paired segment in intact 5S rRNA). The present conclusions are supported by one- and two-dimensional proton homonuclear Overhauser enhancements in H2O and by temperature variation and Mg2+ titration of the downfield 1H NMR spectrum. The difference between the two conformers is most likely due to difference in helical tightness. Some additional amino proton resonances have also been assigned. PMID- 2331461 TI - Deuterium relaxation and internal motion in solid Li-DNA. AB - As part of an effort to explore the nature of the internal motion in solid polynucleotides, the spectral densities of motion J1(omega 0) and J2(2 omega 0) have been measured for oriented, partially hydrated samples of calf thymus Li-DNA deuterated in the guanine and adenine 8-positions. Both spectral densities increase with increasing hydration level, J1 is found to be 2-5 times larger than J2, and their frequency dependence appears to be omega-1 and omega-3/2, respectively. The large values of the ratio J1/J2 rule out any in-plane torsional motion as the dominant relaxation mechanism in these samples, but a drop in this ratio at high hydration levels (G13 H2O/nucleotide) may indicate increasing contributions from such torsional motion. Although a satisfactory fit to a particular motional model has yet to be achieved, our findings show that the librational motion of the C8-D bond at or below a hydration level of 10 H2O/nucleotide is approximately uniaxial, with correlation times for the motion in the range 0.2-3.0 microseconds. PMID- 2331463 TI - Wheat germ 5S ribosomal RNA common arm fragment conformations observed by 1H and 31P nuclear magnetic resonance spectroscopy. AB - The nonexchangeable protons of the common arm fragment of wheat germ (Triticum aestivum) ribosomal 5S RNA have been observed by means of high-resolution 500-MHz 1H NMR spectroscopy in D2O solution. Although NMR studies on the exchangeable protons support the presence of two distinct solution structures of the common arm fragment (and of the same base-paired segment in intact 5S rRNA), only a single conformation is manifested in the 1H NMR behavior of all of the H6 and H5 pyrimidine and most of the H8/H2 purine protons under the same salt conditions. The nonexchangeable protons near the base-paired helix have been assigned by a sequential strategy. Conformational features such as the presence of a cytidine uridine (C.U) pair at the loop-helix junction and base stacking into the hairpin loop are evaluated from nuclear Overhauser enhancement spectroscopy (NOESY) data. Double-quantum filtered correlation spectroscopy (DQF-COSY) experiments show that most of the 26 riboses are in the C3'-endo conformation. Finally, backbone conformational changes induced by Mg2+ and heating have been monitored by 31P NMR spectroscopy. Our results show that the common arm RNA segment can assume two conformations which produce distinguishably different NMR environments at the base-pair hydrogen-bond imino protons but not at nonexchangeable base or ribose proton or backbone phosphate sites. PMID- 2331464 TI - Interaction between chicken cystatin and the cysteine proteinases actinidin, chymopapain A, and ficin. AB - The cysteine proteinase inhibitor cystatin, from chicken egg white, bound with equimolar stoichiometry to the cysteine proteinases actinidin, chymopapain A, and ficin. The changes of near-ultraviolet absorption and fluorescence induced by the binding differed appreciably for the three enzymes, indicating that these spectral changes arise predominantly from aromatic residues in the proteinases. In contrast, the near-ultraviolet circular dichroism changes were similar for all three enzymes, supporting previous evidence that these changes originate mainly from the single tryptophan residue in cystatin, Trp-104. The pseudo-first-order rate constant for the binding increased linearly with the inhibitor concentration up to as high concentrations as could be measured for the three proteinases. This behavior is consistent with the complexes being formed by simple, bimolecular reactions, as was concluded previously for the reaction of cystatin with active and inactivated forms of papain. The second-order association rate constant varied only about 4-fold, from 2.2 X 10(6) to 9.6 X 10(6) M-1.s-1, for the three enzymes, the higher of these values being similar to that measured previously for the reaction with papain. These observations are consistent with the association rate being governed mainly by the frequency of collision between the binding areas of enzyme and inhibitor. All three cystatin-proteinase complexes dissociated to intact inhibitor, demonstrating reversibility. The dissociation rate constants varied about 20000-fold, from 4.6 X 10(-7) s-1 for ficin to 1.1 X 10(-2) s-1 for actinidin, reflecting substantial differences between the enzymes in the nature of the interactions with the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331465 TI - Modulation of serotonin uptake kinetics by ions and ion gradients in human placental brush-border membrane vesicles. AB - The modulation of serotonin uptake kinetics by Na+, Cl-, H+, and K+ was investigated in brush-border membrane vesicles prepared from normal human term placentas. The presence of Na+ and Cl- in the external medium was mandatory for the function of the serotonin transporter. In both cases, the initial uptake rate of serotonin was a hyperbolic function of the ion concentration, indicating involvement of one Na+ and one Cl- per transport of one serotonin molecule. The apparent dissociation constant for Na+ and Cl- was 145 and 79 mM, respectively. The external Na+ increased the Vmax of the transporter and also increased the affinity of the transporter for serotonin. The external Cl- also showed similar effects on the Vmax and the Kt, but its effect on the Kt was small compared to that of Na+. The presence of an inside-acidic pH, with or without a transmembrane pH gradient, stimulated the NaCl-dependent serotonin uptake. The effect of internal [H+] on the transport function was to increase the Vmax and decrease the affinity of the transporter for serotonin. The presence of K+ inside the vesicles also greatly stimulated the initial rates of serotonin uptake, and the stimulation was greater at pH 7.5 than at pH 6.5. This stimulation was a hyperbolic function of the internal K+ concentration at both pH values, indicating involvement of one K+ per transport of one serotonin molecule. The apparent dissociation constant for K+ was 5.6 mM at pH 6.5 and 4.0 mM at pH 7.5. The effects of internal [K+] on the uptake kinetics were similar to those of internal [H+].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331466 TI - 13C and 15N NMR studies on the interaction between 6,7-dimethyl-8-ribityllumazine and lumazine protein. AB - The interaction between the prosthetic group 6,7-dimethyl-8-(1'-D ribityl)lumazine and the lumazine apoproteins from two marine bioluminescent bacteria, one from a relatively thermophilic species, Photobacterium leiognathi, and the other from a psychrophilic species, Photobacterium phosphoreum, was studied by 13C and 15N NMR using various selectively enriched derivatives. It is shown that the electron distribution in the protein-bound 6,7-dimethyl-8 ribityllumazine differs from that of free 6,7-dimethyl-8-ribityllumazine in buffer. The 13C and 15N chemical shifts indicate that the protein-bound 6,7 dimethyl-8-ribityllumazine is embedded in a polar environment and that the ring system is strongly polarized. It is concluded that the two carbonyl groups play an important role in the polarization of the molecule. The N(3)-H group is not accessible to bulk solvent. The N(8) atom is sp2 hybridized and has delta+ character. Nuclear Overhauser effect studies indicate that the 6,7-dimethyl-8 ribityllumazine ring is rigidly bound with no internal mobility. The NMR results indicate that the interaction between the ring system and the two apoproteins is almost the same. PMID- 2331467 TI - Assignment strategies in homonuclear three-dimensional 1H NMR spectra of proteins. AB - The increase in dimensionality of three-dimensional (3D) NMR greatly enhances the spectral resolution in comparison to 2D NMR. It alleviates the problem of resonance overlap and may extend the range of molecules amenable to structure determination by high-resolution NRM spectroscopy. Here, we present strategies for the assignment of protein resonances from homonuclear nonselective 3D NOE HOHAHA spectra. A notation for connectivities between protons, corresponding to cross peaks in 3D spectra, is introduced. We show how spin systems can be identified by tracing cross-peak patterns in cross sections perpendicular to the three frequency axes. The observable 3D sequential connectivities in proteins are tabulated, and estimates for the relative intensities of the corresponding cross peaks are given for alpha-helical and beta-sheet conformations. Intensities of the cross peaks in the 3D spectrum of pike III parvalbumin follow the predictions. The sequential-assignment procedure is illustrated for loop regions, extended and alpha-helical conformations for the residues Ala 54-Leu 63 of parvalbumin. NOEs that were not previously identified in 2D spectra of parvalbumin due to overlap are found. PMID- 2331468 TI - Effect of tubulin binding and self-association on the near-ultraviolet circular dichroic spectra of colchicine and analogues. AB - Near-UV circular dichroic (CD) spectra of three colchicine analogues that differ at the C-10 position have been obtained in the presence and absence of tubulin. All three colchicine analogues show dramatic alterations in the low-energy near UV CD band upon tubulin binding that cannot be mimicked by solvent, but in no event does the rotational strength of the CD band decrease to nearly zero as in the case of colchicine [Detrich, H. W., III, Williams, R. C., Jr., Macdonald, T. L., & Puett, D. (1981) Biochemistry 20, 5999-6005]. The effect of self association of colchicine and one of the C-10 analogues, thiocolchicine, on the near-UV CD band was also investigated. A qualitative similarity was seen between the near-UV CD spectra of colchicine and thiocolchicine dimers and the spectra of these molecules bound to tubulin. These observations support the previous suggestion that ligands bound to the colchicine site on tubulin may be interacting with an aromatic amino acid in the colchicine binding site [Hastie, S. B., & Rava, R. P. (1989) J. Am. Chem. Soc. 110, 6993-7001]. PMID- 2331469 TI - Lentiginosine, a dihydroxyindolizidine alkaloid that inhibits amyloglucosidase. AB - Lentiginosine, a dihydroxyindolizidine alkaloid, was extracted from the leaves of Astragalus lentiginosus with hot methanol and was purified to homogeneity by ion exchange, thin-layer, and radial chromatography. A second dihydroxyindolizidine, the 2-epimer of lentiginosine, was also purified to apparent homogeneity from these extracts. Gas chromatography of the two isomers (as the TMS derivatives) showed that they were better than 95% pure; lentiginosine eluted at 8.65 min and the 2-epimer at 9.00 min. Both compounds had a molecular ion in their mass spectra of 157, and the NMR spectra demonstrated that both were dihydroxyindolizidines differing in the configuration of the hydroxyl group at carbon 2. Lentiginosine was found to be a reasonably good inhibitor of the fungal alpha-glucosidase, amyloglucosidase (Ki = 1 x 10(-5) M), but it did not inhibit other alpha-glucosidases (i.e., sucrase, maltase, yeast alpha-glucosidase, glucosidase I) nor any other glycosidases. The 2-epimer had no activity against any of the glycosidases tested. PMID- 2331470 TI - High-density-lipoprotein-induced cholesterol efflux from arterial smooth muscle cell derived foam cells: functional relationship of the cholesteryl ester cycle and eicosanoid biosynthesis. AB - Eicosanoids have been implicated in the regulation of arterial smooth muscle cell (SMC) cholesteryl ester (CE) metabolism. These eicosanoids, which include prostacyclin (PGI2), stimulate CE hydrolytic activities. High-density lipoproteins (HDL), which promote cholesterol efflux, also stimulate PGI2 production, suggesting that HDL-induced cholesterol efflux is modulated by eicosanoid biosynthesis. To ascertain the role of endogenously synthesized eicosanoids produced by arterial smooth muscle cells in the regulation of CE metabolism, we examined the effects of cyclooxygenase inhibition on CE hydrolytic enzyme activities, cholesterol efflux, and cholesterol content in normal SMC and SMC-derived foam cells following exposure to HDL and another cholesterol acceptor protein, serum albumin. Alterations of these activities were correlated with cholesterol efflux in response to HDL or bovine serum albumin (BSA) in the presence or absence of aspirin. HDL stimulated PGI2 synthesis and CE hydrolases in a dose-dependent manner. Eicosanoid dependency was established by demonstrating that HDL-induced acid cholesteryl ester hydrolase (ACEH) activity was blocked by aspirin. CE enrichment essentially abrogated HDL-induced PGI2 production in cells which also exhibited decreased lysosomal and cytoplasmic CE hydrolase activities. In CE-enriched cells whose cytoplasmic CE pool was metabolically labeled with [3H]oleate or cLDL containing [3H]cholesteryl linoleate, aspirin did not alter HDL- or BSA-induced net CE hydrolysis or efflux, respectively. Finally, aspirin treatment did not alter the mass of either free or esterified cholesterol content of untreated or CE-enriched SMC following exposure to acceptor proteins. These data demonstrated that CE enrichment significantly reduced HDL-induced activation of CE hydrolytic activity via inhibition of endogenous PGI2 production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331471 TI - Preferential interactions determine protein solubility in three-component solutions: the MgCl2 system. AB - The correlation between protein solubility and the preferential interactions of proteins with solvent components was critically examined with aqueous MgCl2 as the solvent system. Preferential interaction and solubility measurements with three proteins, beta-lactoglobulin, bovine serum albumin, and lysozyme, resulted in similar patterns of interaction. At acid pH (pH 2-3) and lower salt concentrations (less than 2 M), the proteins were preferentially hydrated, while at higher salt concentrations, the interaction was either that of preferential salt binding or low salt exclusion. At pH 4.5-5, all three proteins exhibited either very low preferential hydration or preferential binding of MgCl2. These results were analyzed in terms of the balance between salt binding and salt exclusion attributed to the increase in the surface tension of water by salts, which is invariant with conditions. It was shown that the increase in salt binding at high salt concentration is a reflection of mass action, while its decrease at acid pH is due to the electrostatic repulsion between Mg2+ ions and the high net positive charge on the protein. The preferential interaction pattern was paralleled by the variation of protein solubility with solvent conditions. Calculation of the transfer free energies from water to the salt solutions for proteins in solution and in the precipitate showed dependencies on salt concentration. This indicates that the nature of interactions between proteins and solvent components is the same in solution and in the solid state, which implies no change in protein structure during precipitation. Analysis of the transfer free energies and preferential interaction parameter in terms of the salting-in, salting-out, and weak ion binding contributions has led to the conclusions that, when the weak ion binding contribution is small, the predominant protein-salt interaction must be that of preferential salt exclusion most probably caused by the increase of the surface tension of water by addition of the salt. A necessary consequence of this is salting-out of the protein, if the protein structure is to remain unaltered. PMID- 2331472 TI - Why preferential hydration does not always stabilize the native structure of globular proteins. AB - The observed preferential hydration of proteins in aqueous MgCl2 solutions at low pH and low salt concentration (Arakawa et al., 1990) prompted a scrutiny of possible protein stabilization by MgCl2 under the same conditions, in view of earlier observations in aqueous solutions of sugars, amino acids, and a number of salts that preferential hydration is usually accompanied by the stabilization of the native structure of globular proteins. The results of thermal transition experiments on five proteins (ribonuclease A, lysozyme, beta-lactoglobulin, chymotrypsinogen, and bovine serum albumin) revealed neither significant stabilization nor destabilization of the protein structures by MgCl2 both at acid conditions (except for ribonuclease A, which was stabilized, but to a much smaller extent than by MgSO4) and at higher pH at which MgCl2 displayed little preferential hydration. This was in contrast to the great stabilizing action of MgSO4 at the same conditions. 2-Methyl-2,4-pentanediol (MPD), which gives a very large preferential hydration of native ribonuclease A at pH 5.8 [Pittz & Timasheff (1978) Biochemistry 17, 615-623], was found to be a strong destabilizer of that protein at the same conditions. Analysis of the preferentially hydrating solvent systems led to their classification into two categories: those in which the preferential hydration is independent of solution conditions and those in which it varies with conditions. The first always stabilize protein structure, while the second do not. In the first category the predominant interaction is that of cosolvent exclusion, determined by solvent properties, with the protein being essentially inert. In the second category interactions are determined to a major extent by the chemical nature of the protein surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331473 TI - Differential labeling of the catalytic subunit of cAMP-dependent protein kinase with a water-soluble carbodiimide: identification of carboxyl groups protected by MgATP and inhibitor peptides. AB - The catalytic subunit of cAMP-dependent protein kinase typically phosphorylates protein substrates containing basic amino acids preceding the phosphorylation site. To identify amino acids in the catalytic subunit that might interact with these basic residues in the protein substrate, the enzyme was treated with a water-soluble carbodiimide, 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), in the presence of [14C]glycine ethyl ester. Modification of the catalytic subunit in the absence of substrates led to the irreversible, first-order inhibition of activity. Neither MgATP nor a 6-residue inhibitor peptide alone was sufficient to protect the catalytic subunit against inactivation by the carbodiimide. However, the inhibitor peptide and MgATP together completely blocked the inhibitory effects of EDC. Several carboxyl groups in the free catalytic subunit were radiolabeled after the catalytic subunit was modified with EDC and [14C]glycine ethyl ester. After purification and sequencing, these carboxyl groups were identified as Glu 107, Glu 170, Asp 241, Asp 328, Asp 329, Glu 331, Glu 332, and Glu 333. Three of these amino acids, Glu 331, Glu 107, and Asp 241, were labeled regardless of the presence of substrates, while Glu 333 and Asp 329 were modified to a slight extent only in the free catalytic subunit. Glu 170, Asp 328, and Glu 332 were all very reactive in the apoenzyme but fully protected from modification by EDC in the presence of MgATP and an inhibitor peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331474 TI - Pyrene eximer mapping in cultured fibroblasts by ratio imaging and time-resolved microscopy. AB - The kinetics of pyrene eximer formation provide a measure of lateral diffusibility in bilayer membranes. Swiss 3T3 fibroblasts were labeled with pyrene, pyrenedecanoic acid (PDA) and 1,3-bis(1 pyrene) propane (BPP) by incubation in the presence of Pluronic F127. Single-cell emission spectra obtained by epifluorescence microscopy (excitation 350 nm) with photodiode array detection showed monomer (380-420 nm) and eximer (475 nm) peaks. The eximer-to monomer fluorescence ratio (E/M) increased with increasing temperature and loading time. Time-resolved microscopy studies of fibroblasts labeled with PDA for 15 min gave monomer and eximer lifetimes of 101 and 78 ns, respectively, with a monomer-to-eximer conversion rate of 0.02 ns-1. E/M ratio images were obtained with a microchannel plate intensifier and CCD camera at 350-nm excitation and 405 +/- 5 nm (monomer) and greater than 470-nm (eximer) emission wavelengths. E/M ratios of PDA showed spatial variation across the cell with highest ratios at the peripheral plasma membrane. These results establish the methodology to label cells with pyrene eximer-forming probes and to image eximer distributions in membranes of intact cultured cells. Eximer-to-monomer fluorescence ratios are sensitive to maneuvers that alter the membrane physical state and should be of utility in examining the cellular regulation of membrane fluidity. PMID- 2331475 TI - Ovothiols as free-radical scavengers and the mechanism of ovothiol-promoted NAD(P)H-O2 oxidoreductase activity. AB - Racemic ovothiol A [(+/-)-1a] and the ovothiol model compound 1,5-dimethyl-4 mercaptoimidazole (DMI, 2) were found to scavange the free radicals Fremy's salt (4) and Banfield' radical (5) much more rapidly than did the thiol antioxidant glutathione. Ovothiol A also scavenges the tyrosyl radical, with efficiency comparable to that of ascorbic acid and the tocopherol analogue trolox (3). The ovothiol model compound DMI was found to scavenge superoxide with a rate constant comparable to that of the reaction between superoxide and glutathione. These results suggest both a free-radical scavenging role for the ovothiols and a mechanism by which the ovothiols confer NAD(P)H-O2 oxidoreductase activity upon the enzyme ovoperoxidase. Investigation of this mechanism implicates the ovothiol thiyl radical and the NAD radical as key intermediates. The ovothiyl radical appears to be unreactive toward oxygen but highly reactive toward NADH. An estimate of the one-electron oxidation potential of the ovothiol anion is presented. The physical basis for the stability of the ovothiol free radical is discussed. PMID- 2331476 TI - Inhibition by trimethylamine of methylamine oxidation by Paracoccus denitrificans and bacterium W3A1. AB - Trimethylamine, a common substrate for methylotrophic growth, specifically inhibited methylamine-dependent respiration by Paracoccus denitrificans and bacterium W3A1. These effects were caused by the specific inhibition by trimethylamine of the periplasmic quinoprotein methylamine dehydrogenase. Steady state kinetic analysis of the effect of trimethylamine on methylamine oxidation by methylamine dehydrogenase indicated that the inhibition was a mixed type. Apparent Ki values for trimethylamine of 1.1 mM and 4.7 mM, respectively, were obtained for the P. denitrificans and bacterium W3A1 enzymes. Methylamine dependent oxygen consumption by each bacterium was inhibited either by preincubation of cells with trimethylamine prior to the addition of substrate or by addition of trimethylamine to actively respiring cells. Formate-dependent respiration was not inhibited by trimethylamine. A scheme is proposed which describes a regulatory role for trimethylamine in the metabolism and dissimilation of methylamine by methylotrophic bacteria. PMID- 2331477 TI - Perfluorooctane sulfonamide: a structurally novel uncoupler of oxidative phosphorylation. AB - The effects of sulfluramide (N-ethylperfluorooctane sulfonamide) and perfluorooctane sulfonamide (DESFA) on isolated rabbit renal cortical mitochondria (RCM) were examined. Sulfluramid (1-100 microM) and DESFA (0.5-50 microM) increased state 4 respiration of RCM respiring on pyruvate/malate or succinate in a concentration dependent manner in the absence of a phosphate acceptor. In addition, both sulfluramid and DESFA increased state 4 respiration in the presence of oligomycin, an inhibitor of F0F1-ATPase. The effects of sulfluramid (200 microM), DESFA (100 microM), and the known protonophore and uncoupler of oxidative phosphorylation, carbonyl cyanide p trifluoromethoxyphenylhydrazone (FCCP) (1 microM), on RCM proton movement were examined directly by monitoring extramitochondrial pH and indirectly by monitoring passive mitochondrial swelling. Immediately upon addition, DESFA and FCCP, but not sulfluramid, dissipated the RCM proton gradient and caused RCM to swell in solutions of NaCl or NH4Cl. These results show that DESFA uncouples oxidative phosphorylation by acting as a protonophore. RCM were shown to metabolize sulfluramid to DESFA which suggests that the increase in state 4 respiration observed with sulfluramid is due to DESFA. DESFA is unique in that it is one of two uncouplers that does not contain a ring structure and thus may be a useful model in the study of oxidative phosphorylation. PMID- 2331478 TI - The interaction of phosphorylase a with D-glucose displays alpha stereospecificity. AB - Half-maximal inhibition of phosphorylase a required a much lower concentration of alpha-D-glucose (4 mM) than of the beta-anomer (14 mM) and of 1-deoxyglucose (about 25 mM). beta-D-Glucose was almost ineffective at concentrations of 1-2.5 mM, but at 50 mM the two anomers were equipotent. A similar picture emerged when the stimulatory effects of the glucose anomers and of 1-deoxyglucose were investigated on the inactivation of phosphorylase by phosphorylase phosphatase. However, upon addition of either glucose anomer (5-20 mM) to a suspension of isolated hepatocytes, the inactivation of phosphorylase occurred at the same rate. It is shown that, in the latter conditions, the rate of intracellular mutarotation considerably exceeds the rate of glucose transport. This results presumably in a rapid anomeric equilibrium in the liver cells. PMID- 2331479 TI - 13C-NMR of Clostridium pasteurianum ferredoxin after reductive methylation of the amines using [13C]formaldehyde. AB - Clostridium pasteurianum 2(4Fe-4S) ferredoxin has been reductively methylated using [13C]formaldehyde and sodium cyanoborohydride. Lys3 and the N-terminal alanine, the only amines in the protein, are both dimethylated by this procedure. 13C-NMR titration of the apo, oxidized and reduced modified ferrodoxin indicate that the lysine pK is slightly over 10 in all three forms of the protein. In contrast, the N-terminal alanine shifts from a pK of 7.7 in the apoprotein to greater than 9 in both the oxidized and reduced modified ferredoxin. The unexpectedly high pK observed for the N-terminus is consistent with the presence of an ion pair in both the oxidized and reduced native forms of the protein. The methylated ferrodoxin is considerably less stable than the native protein, indicating an important role for the amines in protein stability. PMID- 2331480 TI - The structure-activity relationship of the papain hydrolysis of N-benzoylglycine esters. AB - The relationship between structure and the Michaelis-Menten constants (Km) for the papain hydrolysis of a series of 37 N-benzoylglycine esters was investigated. The series studied comprises a wide range of aromatic and aliphatic esters with a 5000-fold variation in their Km constants and essentially constant kcat values. It was found that the variation in the Km constants could be rationalized by the following quantitative structure-activity relationship (QSAR): log 1/Km = 8.13F + 0.33Z + 1.27II3' + 1.95. In this equation F is the field inductive parameter, II3' is the hydrophobic constant for the more lipophilic of the two possible meta substituents and Z is the Van der Waals distance from oxygen through the end of the molecule, in the direction of the 4 position of the aromatic ester moiety. PMID- 2331481 TI - The site of amino acid addition to posttranslationally modified proteins of regenerating rat sciatic nerves. AB - The posttranslational modification of proteins by amino acids has been described in a variety of biological systems. These reactions occur at low levels in intact sciatic nerves of rats but are increased 10-fold following nerve injury and during subsequent regeneration of the nerve. While it has been shown in brain and liver that the site of addition of Arg is to the N-terminus, there is no information on the location at which the other amino acids add on to targeted proteins nor the site of addition of Arg in regenerating nerves. In the present study, we have used manual micro-Edman degradation combined with HPLC, and digestion with carboxypeptidase A and B to determine the site of addition of various amino acids to targeted proteins. Of the 3H-labelled amino acids incorporated posttranslationally into proteins of regenerating sciatic nerves (Arg, Lys, Leu, Phe, Val, Ala, Pro and Ser), only [3H]Arg was found to be present at the N-terminus. To determine whether amino acid additions were occurring at the C-terminus, proteins modified by two of the amino acids incorporated in greatest amounts (Lys and Leu) were incubated with specific carboxypeptidases. [3H]Leucine was not liberated following incubation with carboxypeptidase, suggesting that Leu is not added at the C-terminus of modified proteins. Under similar conditions, some [3H]Lys was liberated, but in amounts not significantly different from controls incubated without carboxypeptidase, indicating a non specific degradation of Lys modified proteins rather than a specific release of Lys from the C-terminus. These experiments show that in regenerating sciatic nerves of rats, Arg is the only amino acid added posttranslationally to the amino terminus of target proteins, and that Leu, and probably Lys, are not conjugated to proteins at the C-terminus. PMID- 2331482 TI - Regulation of the calcium-activated neutral proteinase (CANP) of bovine brain by myelin lipids. AB - Since calcium-activated neutral proteinase (CANP; calpain) activation occurs at the plasmalemma and the enzyme is found in myelin, we examined myelin lipid activation of brain CANP. Purified lipids were dried, sonicated and incubated with purified myelin CANP. The CANP was assayed using [14C]azocasein as substrate and the Ca2+ concentration ranged from 2 microM for muCANP to 5 mM for mCANP. Phosphatidylinositol (PI), phosphatidylserine (PS) and dioleoylglycerol stimulated the mCANP activity by 193, 89 and 78%, respectively. PI stimulated both m- and muCANP in a concentration-dependent manner, while phosphatidylcholine was least effective. Cerebroside and sulfatide at higher concentrations (750 microM) were stimulatory. The phospholipid (PL)-mediated activation was inhibited by the PL-binding drug trifluoperazine. PI reduced the Ca2+ requirement for CANPs significantly (20-fold). These results suggest that acidic lipids and particularly acidic phospholipids activate membrane CANP. PMID- 2331483 TI - Stabilization, purification and crystallization of catalytic subunit of cAMP dependent protein kinase from bovine heart. AB - The catalytic subunit of cAMP-dependent protein kinase purified from bovine heart was significantly stabilized by non-ionic detergents. Freezing and thawing did not cause a significant decrease in the enzyme activity in the presence of 0.1% Tween 80. A very convenient method for purification and crystallization of the catalytic subunit was also described. PMID- 2331484 TI - Reduction of disulfides in urokinase and insertion of a synthetic peptide. AB - Abbokinase is a commercially available two-chain lower molecular weight urinary plasminogen activator (u-PA) with low affinity for fibrin. Therefore, therapeutic use of this u-PA form (UK) may cause activation of not only clot-bound plasminogen but also systemic plasminogen. Since this form of UK contains a 13 residue peptide remnant of the A chain disulfide-linked to the catalytic B chain, disulfide-exchange could allow replacement of this native peptide with peptides of desired clot-directed properties. We report here a method in which native peptide was partially removed by subjecting UK to 1-100 mM dithiothreitol (DTT), in the presence of arginine. Arginine (250 mM) was found to slow the rate of release of the peptide by 2-fold, to slow the loss in enzymatic activity by about 9-fold and to limit the extent of disulfide reduction. Upon dialysis to remove DTT from the reduced UK mixture, the disulfides reformed and enzymatic activity was regained. Synthetic peptide added at this point became incorporated to the level of about 0.4 mol/mol UK. This method should be very useful for developing UK derivatives with altered affinities toward fibrin clots. PMID- 2331485 TI - Selective inactivation of various acyl-CoA dehydrogenases by (methylenecyclopropyl)acetyl-CoA. AB - Inactivation of five distinct acyl-CoA dehydrogenases by (methylenecyclopropyl)acetyl-CoA (MCPA-CoA), the toxic metabolite of hypoglycin from unripe ackee fruit, was investigated using purified enzyme preparations. Short-chain acyl-CoA (SCADH), medium-chain acyl-CoA (MCADH) and isovaleryl-CoA (IVDH) dehydrogenases were severely and irreversibly inactivated by MCPA-CoA, while 2-methyl-branched chain acyl-CoA dehydrogenase (2-meBCADH) was only slowly and mildly inactivated. Long-chain acyl-CoA dehydrogenase (LCADH) was not significantly inactivated, even after prolonged incubation with MCPA-CoA. Inactivation of SCADH, MCADH and IVDH was effectively prevented by the addition of substrate. This mode of inactivation by MCPA-CoA explains the urinary metabolite profile in hypoglycin treated-rats, which includes large amounts of metabolites from fatty acids and leucine, and relatively small amounts of those from valine and isoleucine. Spectrophotometric titration of SCADH and MCADH with MCPA-CoA, together with the protective effects of substrate, indicates that MCPA CoA is acted upon by, and exerts in turn irreversible inactivation of, SCADH and MCADH, confirming that MCPA-CoA is a suicide inhibitor (Wenz et al. (1981) J. Biol. Chem. 256, 9809-9812). Spectrophotometric titration data of LCADH and MCPA CoA is typical of non-reacting CoA ester. PMID- 2331486 TI - Comparative analysis of collagens solubilized from human foetal, and normal and osteoarthritic adult articular cartilage, with emphasis on type VI collagen. AB - The different collagen types were extracted sequentially, by 4 M guanidinium chloride and pepsin, from human foetal and normal and osteoarthritic adult articular cartilage. They were characterized by electrophoresis and immunoblotting. Most of the collagenous proteins present in articular cartilage from young human foetuses were solubilized: almost 40% of the total collagen was extracted in the native form with 4 M guanidinium chloride. Type VI collagen was detected in this fraction as high-molecular-mass chains (185-220 kDa) and a low molecular-mass chain (140 kDa). Type II, IX and XI collagens were also present, but were extracted more extensively by pepsin digestion. Comparative analysis of normal and osteoarthritic cartilage from adults reveals some major differences: an increase in the solubility of the collagen and modifications of soluble collagen types in osteoarthritic cartilage. Furthermore, type VI collagen was present at a higher concentration in guanidinium chloride extracts of osteoarthritic cartilage than those of normal tissue. This finding was corroborated by electron microscopic observations of the same samples: abundant (100 nm) periodic fibrils were observed in the disorganized pericellular capsule of cloned cells in osteoarthritic cartilage. In normal tissues the pericellular zone was more compact and contained only a few such banded fibrils. The differences in the collagen types solubilized from normal and osteoarthritic cartilage, although corresponding to a minor proportion of the total collagen, demonstrate that important modifications in chondrocyte metabolism and in the collagenous network do occur in degenerated cartilage. PMID- 2331487 TI - Dissociation and aggregation of D-glyceraldehyde-3-phosphate dehydrogenase during denaturation by guanidine hydrochloride. AB - The inactivation of lobster muscle D-glyceraldehyde-3-phosphate dehydrogenase (D glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) (GAPDH) during guanidine hydrochloride (GdnHCl) denaturation has been compared with its state of aggregation and unfolding, by light scattering and fluorescence measurements. The enzyme first dissociates at low concentrations of GdnHCl, followed by the formation of a highly aggregated state with increasing denaturant concentrations, and eventually by complete unfolding and dissociation to the monomer at concentrations of greater than 2 M GdnHCl. The aggregation and final dissociation correspond roughly with the two stages of fluorescence changes reported previously (Xie, G.-F. and Tsou, C.-L. (1987) Biochim. Biophys. Acta 911, 19-24). Rate measurements show a very rapid inactivation, the extents of which increase with increasing concentrations of GdnHCl. This initial rapid phase of inactivation which takes place before dissociation and unfolding of the molecule is in agreement with the results obtained with other enzymes, that the active site is affected before noticeable conformational changes can be detected for the enzyme molecule as a whole. A scheme for the steps leading to the final denaturation, and dissociation of the enzyme to the inactive and unfolded monomer, is proposed. PMID- 2331488 TI - Comparison of inactivation and conformational changes of D-glyceraldehyde-3 phosphate dehydrogenase during thermal denaturation. AB - The inactivation of D-glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde 3-phosphate:NAD+ oxidoreductase (phosphorylating) EC 1.2.1.12) (GAPDH) during thermal denaturation has been compared to its dissociation-aggregation measured by light scattering and changes in secondary structure measured by CD in the far ultraviolet. The inactivation at 38.5 degrees C consists of two stages. The rate of the first stage is too fast to be followed by conventional methods. The extent of this fast stage inactivation increases with increasing temperature and, more markedly, with increasing pH. At this stage, the inactivation is reversible and no appreciable dissociation or change in secondary structure can be detected. The secondary structure of the enzyme is relatively heat stable, showing no appreciable change at 38.5 degrees C. At this temperature, the enzyme first dissociates within several minutes probably into dimers and with prolonged heating, it becomes irreversibly aggregated. The above results are in accord with the earlier suggestion, based on results obtained during denaturation of a number of enzymes by guanidine hydrochloride (GdnHCl) and urea, that for some enzymes the active site is situated in a region more susceptible to perturbation than the molecule as a whole (Tsou, C.-L. (1986) Trends Biochem. Sci. 11, 427). PMID- 2331489 TI - The interaction of rabbit muscle aldolase with NADH. AB - Fluorescence studies on both the emission of aldolase and NADH bound to the enzyme were carried out. Aldolase was found to bind four molecules of NADH with KD = 6.0 +/- 0.3 microM. KD values for NADPH and NAD+ were 41 +/- 4 microM and 140 +/- 30 microM, respectively. The affinity to NADH was comparable with that of some NAD-dependent dehydrogenases, and was not affected by the substrate or the inhibitor. PMID- 2331490 TI - Pattern-recognition by an artificial network derived from biologic neuronal systems. AB - A novel artificial neural network, derived from neurobiological observations, is described and examples of its performance are presented. This DYnamically STable Associative Learning (DYSTAL) network associatively learns both correlations and anticorrelations, and can be configured to classify or restore patterns with only a change in the number of output units. DYSTAL exhibits some particularly desirable properties: computational effort scales linearly with the number of connections, i.e., it is O(N) in complexity; performance of the network is stable with respect to network parameters over wide ranges of their values and over the size of the input field; storage of a very large number of patterns is possible; patterns need not be orthogonal; network connections are not restricted to multi layer feed-forward or any other specific structure; and, for a known set of deterministic input patterns, the network weights can be computed, a priori, in closed form. The network has been associatively trained to perform the XOR function as well as other classification tasks. The network has also been trained to restore patterns obscured by binary or analog noise. Neither global nor local feedback connections are required during learning; hence the network is particularly suitable for hardware (VLSI) implementation. PMID- 2331491 TI - Temporal correlations in modulated evoked responses in the visual cortical cells of the cat. AB - We analysed evoked responses recorded from 97 cells in the visual cortex of 4 adult cats and 8 kittens, stimulated by a drifting sinusoidal grating. A Fourier analysis of the responses allowed us to select 30 cells showing a clear modulating response (relative modulation index greater than 1). The 162 records from these selected cells were scanned to detect precise temporal correlations in the form of replicating triplets and associated "ghost" doublets. Temporal correlations of this nature were observed in these cells. They are about 10 times more abundant in adult cats than in kittens, and mostly observed in infragranular cortical layer cells. The possible role of these precise temporal patterns in information processing in the brain is examined, as well as the relation between this type of temporal correlation with coherent oscillations and principal components waveforms. PMID- 2331492 TI - Changes with background in the linear model of the transient visual system. AB - There is evidence that the transient channel of temporal human vision behaves as a linear filter for small excursions around a steady background level. The linear filter characteristics depend on the background level. From experimentally obtained impulse responses of the transient channel the linear filter can be modelled and parametrized. This has been done for two different background levels. The two sets of estimated parameters at these two levels show a shift in the parameters which can be described by a single multiplication factor. This result was extrapolated to arbitrary background levels by postulating that each change in background level can be described by a multiplication factor. This leads to an assumption on the variation of the parameters of the linear filter of the transient channel with changes in the background level. This assumption is tested by simulating the system for different parameter sets of the linear filter. The simulations give a good agreement with experimental data on threshold versus-duration curves and de Lange curves. The (minor) quantitative differences in simulations and experimental data can be explained. PMID- 2331493 TI - Voiced images, imagined voices. PMID- 2331494 TI - Age-adjusted threshold values for reduced REM latency in unipolar depression using ROC analysis. AB - To determine an age-adjusted, clinically meaningful depressive diathesis, we have implemented Receiver Operator Characteristic (ROC) analysis for mean rapid eye movement (REM) latency in patients with unipolar depression. Depressed patients were compared with age-matched normal control subjects. Sensitivity and specificity estimates were calculated for selected threshold values on the ROC curves as well as for the Research Diagnostic Criteria endogenous/nonendogenous subtype. The mean REM latency value of 65.0-66.0 min was most sensitive and specific for depressed patients aged 35-72. The threshold value of 70.0 min appeared optimally sensitive and specific for depressed patients aged 20-34. There was no effect of age on REM latency in the normal control sample. Among depressed patients there was an effect of age but this was clearly observable only in nonendogenous depressed patients. PMID- 2331495 TI - Quantitative analyses of plasma cholinesterase isozymes in haloperidol-treated rats. AB - We describe a quantitative slab gel electrophoresis procedure that allows quantitative determination of plasma levels of discrete cholinesterase isozymes. Using this method, the effects of haloperidol treatment on plasma cholinesterase isozyme levels were examined in normal rats. Eight isozymes were detected by enzymatic reaction with either of two substrates (alpha-naphthyl acetate, NA; acetylthiocholine iodide, AcTCh), and then quantified using densitometric scanning. With AcTCh substrate, the activities of two major isozymes (1 and 2) were found to be linear with increasing quantities of applied plasma. With NA as substrate, Iso-OMPA (a pseudocholinesterase inhibitor) inhibited activities of all isozymes, except isozymes 2 and 8. With either substrate, BW284C51 (acetylcholinesterase inhibitor) inhibited 100% and 13% of activity of isozymes 2 and 8, respectively, and with AcTCh substrate, 37% of isozyme 1. Based on the differential patterns of substrate specificity and action of inhibitors, and the reproducibility of patterns, we propose that these isozymes represent distinct molecular species. Short-term (14 days) and long-term (45 days) haloperidol treatment both resulted in altered levels of specific cholinesterase (ChE) isozymes. On the average, with AcTCh substrate, haloperidol treatment increased levels of isozymes 1 and 2 by 30% and 8%, respectively, after 14 days, and by 50% and 30%, respectively, after 45 days. Isozymes 3 through 8 showed minor changes. Plasma levels of isozymes 1 and 2 returned to baseline pretreatment values after a 40-day drug-free period. No significant change was observed after either short- or long-term treatment with clozapine, imipramine, or saline, or after an acute (less than 5 days) haloperidol treatment. No change was noted in RBC-ChE levels as function of treatment. These findings indicate that, in the rat, chronic haloperidol treatment results in differential changes in the plasma levels of discrete ChE isozymes. We have suggested that these changes reflect an alteration of central dopaminergic-cholinergic balance. PMID- 2331496 TI - Tissue aluminum concentrations stability over time, relationship to age, and dietary intake. AB - Aluminum concentration was measured in serum, whole blood, hair, and urine by neutron activation analysis. Seventy-six nondemented subjects were investigated. Not all assays were done on all subjects (e.g., serum aluminum on 76 subjects, whole blood aluminum on 42 subjects), but tissue aluminum concentrations were estimated on more than one occasion on 32 subjects. The mean +/- SD aluminum concentration in serum was 0.219 +/- 0.063 micrograms/ml (N = 76), in whole blood 0.368 +/- 0.091 micrograms/ml (N = 42), in urine 0.092 +/- 0.076 micrograms/ml (N = 42), and in hair 6.42 +/- 2.22 micrograms/g (N = 42). Using product moment correlation coefficient there was no significant correlation between age and tissue aluminum concentrations, nor between dietary intake of aluminum and tissue aluminum. The tissue aluminum concentrations were not stable over time even when dietary intake was constant. Tissue aluminum concentrations were measured in 14 patients after 7 days of dietary control and repeated approximately 6 weeks later, again after 7 days of dietary control. There was no significant correlation between the two estimations in any tissue measured. These results suggest that raised tissue aluminum concentrations reported in Alzheimer's disease are not an exaggeration of a normal ageing process, are not likely to be simply secondary to increased dietary aluminum intake, and that Alzheimer's disease does not represent the chronic toxic effect of moderately raised aluminum levels at the upper end of the normal distribution. PMID- 2331497 TI - Comparisons of plasma and salivary cortisol determinations for the diagnostic efficacy of the dexamethasone suppression test. AB - The current status of the saliva dexamethasone suppression test (DST) is discussed and results from the literature reviewed. Evidence is presented that demonstrates that the efficacy of the salivary-based test is equal to that of the plasma DST provided that specifically developed radioimmunoassays are used for determination of salivary cortisol. Such evidence relied on measurement of cortisol in 300 matched samples of plasma and saliva provided by patients admitted to a routine psychiatric ward over a 2-year period. The results according to diagnosis (DSM-III categories) were in line with those generally reported. The influence of anticholinergic medication was examined: this had no significant effects on the performance of the plasma or salivary-based DST. PMID- 2331498 TI - Platelet MAO in subtypes of alcoholism. AB - A number of investigators have observed low platelet monoamine oxidase (MAO) activity in alcoholism. There is also preliminary evidence suggesting that low enzyme activity is principally associated with one of two putative subtypes of alcohol dependence, i.e., type II (male limited). The results of this study are consistent with two previous reports of reduced platelet MAO activity in type II male alcoholics as compared with type I male alcoholics and normal, healthy male controls. Type I (milieu-limited) alcoholics showed a smaller reduction in enzyme activity. The observed differences do not appear to be related to concurrent use of other psychoactive substances, characteristic differences in age between type I alcoholics and type II alcoholics, antisocial personality disorder, or variation in platelet size. Low platelet MAO activity in alcoholics is possibly related to both state and trait factors and may be a useful biochemical measure to assist with subtyping. PMID- 2331499 TI - Adrenocortical sensitivity to low-dose ACTH administration in depressed patients. PMID- 2331500 TI - Humming, auditory hallucinations, and dystonia. PMID- 2331501 TI - The vacuum UV CD bands of repeating DNA sequences are dependent on sequence and conformation. AB - CD spectra were obtained for eight synthetic double-stranded DNA polymers down to at least 175 nm in the vacuum uv. Three sets of sequence isomers were studied: (a) poly[d(A-C).d(G-T)] and poly[d(A-G).d(C-T)], (b) poly[d(A-C-C).d(G-G-T)] and poly[d(A-C-G).d(C-G-T)], and (c) poly[d(A).d(T)], poly[d(A-T).d(A-T)], poly[d(A-A T).d(A-T-T)], and poly[d(A-A-T-T).d(A-A-T-T)]. There were significant differences in the CD spectra at short wavelengths among each set of sequence isomers. The (G.C)-containing sequences had the largest vacuum uv bands, which were positive and in the wavelength range of 180-191 nm. There were no large negative bands at longer wavelengths, consistent with the polymers all being in right-handed conformations. Among the set of sequences containing only A.T base pairs, poly[d(A).d(T)] had the largest vacuum uv CD band, which was at 190 nm. This CD band was not present in the spectra of the other (A.T)-rich polymers and was absent from two first-neighbor estimations of the poly[d(A).d(T)] spectrum obtained from the other three sequences. We concluded that the sequence dependence of the vacuum uv spectra of the (A.T)-rich polymers was due in part to the fact that poly[d(A).d(T)] exists in a noncanonical B conformation. PMID- 2331502 TI - Small-angle neutron scattering study of the structure of protein/detergent complexes. AB - Small-angle neutron scattering (SANS) was used to study the structure of protein/sodium dodecylsulfate complexes. Two water soluble proteins, bovine serum albumin (BSA) and ovalbumin (OVA), were used. The protein concentration was kept constant at 1 wt %, and protein/detergent wt ratio varied between 1/1, 1/1.5, 1/2 and 1/3. Absolute intensities of SANS distributions were analyzed by a fractal model. Analyses of large Q portions of SANS distributions established that sodium dodecylsulfate (SDS) molecules bound to a protein/SDS complex form micelle-like clusters. On the other hand, analyses of small Q portions of SANS distributions clearly showed that the arrangement of micelle-like clusters resembles a fractal packing of spheres. We showed that a protein/SDS complex can be characterized by four parameters extracted from the scattering experiment, namely, the average micelle size and its aggregation number, the fractal dimension characterizing the conformation of the micellar chains, the correlation length giving the extent of the unfolded polypeptide chains, and the numbers of micelle-like clusters in the complex. PMID- 2331503 TI - Structural analysis of purified human tracheobronchial mucins. AB - Light scattering has been used to investigate the structure of human tracheobronchial mucin glycoproteins (HTBM) from the sputum of cystic fibrosis patients. The specimen was extracted using 6M guanidinium hydrochloride solution and fractionated by gel exclusion chromatography on Sephacryl S-1000. The fractionated HTBM was purified by density gradient ultracentrifugation. Purity of the resulting material was confirmed by SDS polyacrylamide gel electrophoresis and uv spectroscopy. Light scattering measurements on the fractionated mucins yield weight-average molecular weights Mw, and z-average radii of gyration Rg,z. The native cystic fibrosis HTBM consisted of a high molecular weight fraction with Mw = 9.3 X 10(6) daltons and a lower molecular weight fraction containing partly degraded mucins. After reduction and carboxymethylation of the high molecular weight native fraction, the resulting material was separated into three pools with Mw values of 5.1 X 10(6), 1.6 X 10(6), and 400,000. The derived molecular weights for the protein cores Mp,w, and the experimental radii of gyration are found to be consistent with the Mp,w -Rg relation established previously for submaxillary, cervical, and gastric mucins. These results imply that HTBM has the same extended-coil conformation reported for other mucins and has a molecular structure consisting of subunits, linked into linear chains via covalent (disulfide) bonds. PMID- 2331504 TI - Structure and dynamics of M13mp19 circular single-strand DNA: effects of ionic strength. AB - Dynamic and static light scattering, CD, and optical melting experiments have been conducted on M13mp19 viral circular single-strand DNA as a function of NaCl concentration. Over the 10,000-fold range in concentration from 100 microM to 1.0 M NaCl, the melting curves and CD spectra indicate an increase in base stacking and stability of stacked regions with increased salt concentration. Analysis of dynamic light scattering measurements of the single-strand DNA solutions as a function of K2 from 1.56 to 20 X 10(10) cm-2 indicates the collected autocorrelation functions are biexponential, thus revealing the presence of two decaying dynamic components. These components are taken to correspond to (1) global translational motions of the molecular center of mass and (2) motions of the internal molecular subunits. From the evaluated relaxation rates of these components, diffusion coefficients D0 and Dplat are determined. The center of mass translational diffusion coefficient D0, varies in a nonmonotonic manner, by 10%, from 3.75 X 10(-8) to 3.39 X 10(-8) cm2/s over the NaCl concentration range from 100 microM to 1.0 M. Likewise, the radius of gyration RG, obtained from static light scattering experiments, varies by 15% from 699 to 830 A over the same NaCl range Dplat, the diffusion coefficient of the internal subunits, displays a different dependence on the NaCl concentration and decreases, by nearly 22% in a titratable fashion, from 12.46 X 10(-8) to 10.26 X 10(-8) cm2/s, when the salt is increased from 100 microM to 1.0 M. A semiquantitative interpretation of these results is provided by analysis of the light scattering data in terms of the circular Rouse-Zimm chain. Rouse-Zimm model parameters are estimated from the experimental results, assuming the circular chains are composed of a fixed number of Gaussian segments, N + 1 = 15. The rms displacement of the internal segments, b, is estimated to be the smallest (442 A) in 100 mM NaCl. Increases of b to 467 A in 100 microM and 524 A in 1.0 M NaCl are observed. Meanwhile, the hypothetical friction factor of the internal subunits, f, progressively increases as the NaCl concentration is raised. It is inferred from the evaluated Rouse-Zimm model parameters that both the static flexibility of the circular chain and diffusive displacements of the internal subunits decrease with increases in NaCl concentration from 100 mM to 1.0 M.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2331505 TI - Electrostatic forces at helix-coil boundaries in DNA. AB - The Tm of internal loop-forming (dA.dT)N domains in pBR322 DNA has been measured over a tenfold range of [Na+]. The slopes SN = dTm/d log [Na+] are linear and decrease in magnitude with decreasing loop size N, signaling a reduction in Na+ released during the transition of these domains to the coil state. Values of SN decrease linearly with increasing N-1 in accordance with the expectation of a simple model for the occurrence of a gradient of long-range electrostatic forces at helix-coil boundaries, and extrapolate almost precisely to the value of S infinity observed for (dA.dT) infinity. These results indicate (1) less counterion is released per phosphate residue from the finite loop than from the infinite-sized loop, and (2) the difference in binding is constant for each boundary formed and independent of the size of the loop within the range examined: approximately 350 base pair (bp) greater than N greater than 71 bp. The slope of the dependence of SN on N-1 indicates the region of higher charge density at the boundary extends at least 18 A into the coil and probably 40-50 A before dropping to a value characteristic of the unperturbed coil. The free energy for excess counterion binding at boundaries can be expressed by -delta G/RT = 10.47 log[Na+] + 5.234 When the loop entropy function in a statistical mechanical algorithm for the dissociation of DNA is weighted by this quantity, calculated Tm are seen to vary by only +/- 0.09 degrees C from observed. PMID- 2331506 TI - 17O- and 14N-NMR studies of Leu-enkephalin and enkephalin-related fragments in aqueous solution. AB - 17O- and 14N-nmr chemical shifts and line widths of the carboxyl and amino terminal groups of Leu-enkephalin--Tyr-Gly-Gly-Phe-[17O]Leu-Oh--and enkephalin related fragments--[17O]Leu-OH, Phe-[17O]Leu-OH, Gly-Phe-[17O]Leu-OH, and Gly-Gly Phe-[17O]Leu-OH--were measured in aqueous solution over the entire H pH range. Enrichment in 17O was achieved by saponification of the corresponding O-methyl esters. Ionization constants and titration shifts were obtained by nonlinear least-squares fits to one-proton titration curves. [17O]Leu-OH exhibits a profound pH-dependent solvation change on deprotonation of the carboxyl group, as shown by 17O- and 14N-nmr line widths. In contrast, the peptides studied do not exhibit pH-dependent conformational (solvation) changes on deprotonation of the carboxyl group, and a head-to-tail intramolecular association between the ionic terminal groups should be excluded. It is shown that the peptides do not exhibit isotropic overall molecular motion and that segmental motion rather than fast internal motion influences the effective correlation times at the sites of the carboxyl oxygens and the amino nitrogen. PMID- 2331507 TI - Light scattering studies of the effect of Ca2+ on the structure of porcine submaxillary mucin. AB - The effects of calcium ions on the solution properties of porcine submaxillary mucin (PSM) have been investigated by static and dynamic light scattering. The weight average molecular weights of PSM fractions are unaffected by the addition of up to 0.5M CaCl2: these data are within experimental error of those for solutions in 0.1M NaCl. The distribution of relaxation frequencies derived from the dynamic data shows the existence of two distinct relaxation modes. The average relaxation times have been interpreted to yield the z-average translational diffusion coefficient and the longest intramolecular relaxation time tau1. A plot of tau1 vs the mean value of 1/Rh-3z is linear, and consistent with plots of such data recorded for PSM in 0.1m NaCl and 6M GdnHCl solutions. However, the tau values and the associated results for the mean value of R-1h-1z in 0.5M CaCl2 are smaller than those determined in 0.1M NaCl. This suggests that the conformation of PSM in CaCl2 solution is more contracted than those in the other two solvents. These results are consistent with the compact packaging of mucin in the secretary granules that have elevated Ca2+ levels. PMID- 2331508 TI - Temperature dependence of enthalpy changes for ethidium and propidium binding to DNA: effect of alkylamine chains. AB - Calorimetric titrations have been performed on the binding of ethidium and propidium to calf thymus DNA at temperatures in the 15-60 degrees C range. Enthalpy changes (delta HB) derived from these experiments performed with the new Omega reaction calorimeter have a precision of +/- 0.10 kcal/mol or less at all temperatures. For ethidium (a monocation), delta HB varies little with temperature, and the heat capacity change (delta CP) for the binding reaction derived from these parameters is 10 cal/deg/mol. In contrast, delta HB changes from -6.5 to -8.1 kcal/mol for DNA binding of propidium (a dication due to a charged amine group at the end of an alkyl chain attached to the phenanthridine ring nitrogen), and delta CP is -57 cal/deg/mol. At 21 degrees C a plot of delta HB vs mole ratio is curved downward for propidium in the 0.08-0.25 range, whereas the same plot at 45 degrees C is a straight line from 0.05 to 0.15 and sharply downward thereafter. Similar plots for ethidium follow the latter pattern between 25 and 50 degrees C. These observations and our analyses of delta HB and delta SB are consistent with the hypothesis that the location in the DNA complex and the rotational motion of the alkylamine chain change substantially over the temperature range in this study. Only near 50 degrees C is delta HB equal for the binding of these two cations to DNA, and caution must be used in analyses of enthalpic effects when the temperature dependence for delta HB is not available. PMID- 2331509 TI - Assignment of the 13C-NMR spectra of virgin and reactive-site modified turkey ovomucoid third domain. AB - The virgin (reactive-site Leu18-Glu19 peptide bond intact) and modified (reactive site Leu18-Glu19 peptide bond hydrolyzed) forms of turkey ovomucoid third domain (OMTKY3 and OMTKY3*, respectively) have been analyzed by proton-detected 1H(13C) two-dimensional single-bond correlation (1H[13C]SBC) spectroscopy. Previous 1H nmr assignments of these proteins [A.D. Robertson, W.M. Westler, and J.L Markley (1988) Biochemistry, 27, 2519-2529; G. I. Rhyu and J. L. Markley (1988) Biochemistry, 27, 2529-2539] have been extended to directly bonded 13C atoms. Assignments have been made to 52 of the 56 backbone 13C alpha-1H units and numerous side-chain 13C-1H groups in both OMTKY3 and OMTKY3*. The largest changes in the 13C chemical shift upon conversion of OMTKY3 to OMTKY3* occur at or near the reactive site, and tend toward values observed in small peptides. Moreover, the side-chain prochiral methylene protons attached to the C gamma of Glu19 and C delta of Arg21 show nonequivalent chemical shifts in OMTKY3 but more equivalent chemical shifts in OMTKY3*. These results suggest that the reactive site region becomes less ordered upon hydrolysis of the Leu18-Glu19 peptide bond. Comparison of 13C alpha chemical shifts of OMTKY3 and bovine pancreatic trypsin inhibitor [D. Bruhuiler and G. Wagner (1986) Biochemistry 25, 5839-5843; N. R. Nirmala and G. Wagner (1988) Journal of the American Chemical Society, 110, 7557-7558] with small peptide values [R. Richarz and K. Wuthrich (1978) Biopolymers, 17, 2133 2141] suggests that 13C alpha chemical shifts of residues residing in helices are generally about 2 ppm downfield of resonances from nonhelical residues. PMID- 2331510 TI - Assessment of protein reorientational diffusion in solution by 13C off-resonance rotating frame spin-lattice relaxation: effect of anisotropic tumbling. AB - The 13C off-resonance rotating frame spin-lattice relaxation technique is applicable to the study of protein rotational diffusion behavior in a variety of experimental situations. The original formalism of James and co-workers (1978) (J. Amer. Chem. Soc. 100, 3590-3594) was constrained by the assumption of random isotropic reorientational motion. Here we include in the formalism anisotropic tumbling, and present the results of computer simulations illustrating the differences between anisotropic and isotropic reorientational motion for the off resonance rotating frame spin-lattice relaxation experiment. In addition, we have included chemical shift anisotropy of the peptide carbonyl carbon as an additional relaxation mechanism contribution, to permit high-field nmr protein rotational diffusion measurements. PMID- 2331511 TI - Electrophoresis and movements of fluorescence pattern after photobleaching of large DNA fragments in agarose gels. AB - By combining electrophoresis with movements of fluorescence pattern after photobleaching (MOFPAP), which is abbreviated as EMOFPAP, we are able to measure electrophoretic mobilities of large DNA fragments in an agarose gel within a fairly short time scale (about 10 min or even down to 1 min). The new method represents a significant improvement in experiment time when compared with the time (typically on the order of hours) required to determine the average electrophoretic mobility of large DNA fragments in agarose gels by means of either conventional gel electrophoresis or pulsed-field gel electrophoresis. In this article, we present the EMOFPAP experimental setup and consider optical conditions, including beam profile geometry and fluorescence pattern formation. A realistic formula that can explain the parameters governing the EMOFPAP method using our present optical setup has been derived. A comparison of results between experimental and computer simulation data is made, and an optimization of the EMOFPAP method is proposed. PMID- 2331512 TI - Assessment of protein reorientational diffusion in solution by 13C off-resonance rotating frame spin-lattice relaxation: effect of polydispersity. AB - The 13C off-resonance rotating frame spin-lattice relaxation technique is applicable to the study of protein rotational diffusion behavior in both model in vitro and in vivo systems. The original formalism of James and co-workers [(1978) J. Am. Chem. Soc. 100, 3590-3594] was constrained by the assumption of random isotropic reorientational motion of a monodisperse protein population. Here we extend the formalism to include polydispersity. Application is made to the alkaline pH induced association of lysozyme, lysozyme-bovine serum albumin mixtures, and to the phase separation of lysozyme salt-water mixtures induced by low temperature. PMID- 2331513 TI - Synthesis, crystal structure, and molecular conformation of peptide N-Boc-L-Pro dehydro-Phe-L-Gly-OH. AB - The peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH was synthesized by the usual workup procedure and finally coupling the N-Boc-L-Pro-dehydro-Phe to glycine. The peptide crystallizes in monoclinic space group P2(1) with a = 8.951(4) A, b = 5.677(6) A, c = 21.192(11) A, beta = 96.97(4) degrees, V = 1069(1) A3, Z = 2, dm = 1.295(5) Mgm-3, and dc = 1.297(4) Mgm-3. The structure was determined by direct methods using SHELXS86. The structure was refined by the block-diagonal least squares procedure to an R value of 0.074 for 1002 observed reflections. The C alpha 2-C beta 2 distance of 1.33(2) A is an appropriate double bond length. The angle C alpha 2-C beta 2-C gamma 2 is 133(1) degrees. The peptide backbone torsion angles are theta 1 = -167(1) degrees, omega 0 = 179(1) degrees, phi 1 = 48(1) degrees, psi 1 = 137(1) degrees, omega 1 = 175(1) degrees, phi 2 = 65(2) degrees, psi 2 = 15(2) degrees, omega 2 = -179(1) degrees, and phi 3 = -166(1) degrees. These values show that the Boc group has a trans-trans conformation while the peptide backbone adopts a beta-turn II conformation, which is stabilized by an intramolecular hydrogen bond of length of 3.05(1) A. The structures of dehydro-Phe containing peptides suggest that the dehydro-Phe promotes the beta-turn II conformation. The five-membered pyrrolidine ring of the Pro residue adopts an ideal C gamma-exo conformation with torsion angles chi 1(1) = -24(1) degrees, chi 2(1) = 34(1) degrees, chi 3(1) = -30(1) degrees, chi 4(1) = 15(1) degrees, and theta 0(1) = 6(1) degrees. The side-chain torsion angles in dehydro-Phe are chi 1(2) = -1(2) degrees, chi 2,1(2) = -176(1) degrees, and chi 2,2(2) = 8(2) degrees. The plane of C alpha 2-C beta 2-C gamma 2 is rotated with respect to the plane of the phenyl ring at 7(1) degrees, which indicates that the atoms of the side chain of dehydro-Phe are essentially coplanar. The molecules form a 2(1) screw axis related hydrogen-bonded rows along the b axis. PMID- 2331514 TI - Simulations of the B-DNA molecular dynamics of d(CGCGAATTCGCG)2 and d(GCGCGCGCGC)2: an analysis of the role of initial geometry and a comparison of united and all-atom models. AB - Molecular dynamics simulations on the sequence d(CGCGAATTCGCG)2 have been carried out using both united atom and all-atom representations, and starting the simulations both from a regular repeating B-DNA structure and from the x-ray single crystal B-DNA structure. An all-atom B-DNA simulation on the sequence d(GCGCGCGCGC)2 has also been carried out, in order to compare it with a previous united atom simulation. The helix repeats, H-bonding, sugar pucker profiles, and average torsional angles are all in the range observed in crystallographic and nmr studies for B-DNA helices. In some of the sequences, there is a significant bend in the DNA helices. The individual helix repeats, with focus on 3'CpG5' and 3'GpC5' units, show the opposite helix repeat to that suggested by Calladine's rules. PMID- 2331515 TI - Solvent effects on protein association and protein folding. AB - Solvent effects on the thermodynamics of two processes--folding of proteins and association between proteins--are examined in detail. A complete inventory of the multitude of solvent effects may be obtained by employing the concept of conditional solvation free energy. This theoretical tool allows for the isolation of specific side-chain effects from the entire protein and for the study of its contribution to the overall free energy change in small model compounds. Some numerical examples are presented, and ways of estimating other cases, for which no relevant experimental data are available, are suggested. Our findings lead to the conclusion that the currently used hydrophobicity scales, based on partition coefficients between water and an organic solvent, are inadequate measures of the contribution of side chains being transferred from water to the interior of the protein. We have also tentatively concluded that correlation between hydrophilic functional groups might be more important than correlations between hydrophobic side chains. PMID- 2331516 TI - Computational analysis of the effects of site-specific phosphate alkylation in the DNA oligomer (d-[GGAATTCC])2. AB - Alkylation of the sugar-phosphate backbone of DNA can result upon exposure to several potent carcinogens, inducing DNA misfunction. In order to assess the structural and energetic changes in DNA helices induced by such alkylation, we have performed AMBER-based analyses on phosphotriester containing analogues of (d [GGAATTCC])2. Fourteen analogues of the nonalkylated oligomer were examined, each bearing a single alkylation of known stereochemistry. Results indicate that although there is minimal effect on the aromatic bases, the presence of a phosphotriester disturbs the sugar-phosphate backbone in complex ways. For most analogues, total minimum energies are lower for the Sp-alkylations than for the Rp-alkylations which point directly into the major groove of the helix; however, different energetic contributions follow different, or no, trends in dependence on alkylation site and/or stereochemistry. Where data is available, experimental nmr results agree with the calculations reported here. PMID- 2331517 TI - Melanin-concentrating hormone: a structural and conformational study based on synthesis, biological activity, high-field NMR, and molecular modeling techniques. AB - A series of Melanin-concentrating hormone (MCH) fragments have been synthesized and their biological activities compared with the parent peptide. The substructural units, 5-14 linear and 5-14 cyclic, have been used as models for MCH-- H-Asp1-Thr-Met-Arg-Cys-Met-Val-Gly-Arg HO-Val17-Glu-Trp-Cys-Pro-Arg-Tyr-Val in 1H-nmr conformational studies. Conformational features predicted by molecular dynamics analyses find support in the nmr experiments. PMID- 2331518 TI - Accessible conformations of melanin-concentrating hormone: a molecular dynamics approach. AB - Molecular dynamics simulations have been used to search for the accessible conformations of the melanin-concentrating hormone (MCH). The studies have been performed on native MCH and two of its peptide fragments, a cyclic MCH(5-14) fragment and a linear MCH(5-14) fragment. An analysis of the molecular dynamics trajectories of the three peptides indicates that two regions of the peptide have characteristic conformational properties that may be important for the biological activity. One is a region around Gly8, which is conformationally mobile, and the other is around Pro13, which shows unusual rigidity. The molecular dynamics simulation results are discussed in terms of backbone structural features like beta turns, side-chain interactions, and orientations of the disulfide bridge. The results of this analysis are used to suggest new analogues that will modify the conformational features of the peptide and further define the conformational requirements for activity. Finally, the results are related to nmr studies of the peptide and reveal agreements between the experimental nuclear Overhauser effect constraints and some of the accessible conformations obtained from the simulation. PMID- 2331519 TI - Thermal behavior of the 760-nm absorption band in photodissociated sperm whale carbonmonoxymyoglobin at cryogenic temperature: dependence on external medium. PMID- 2331520 TI - Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria (Gunther's disease). AB - Congenital erythropoietic porphyria (Gunther's disease) is a rare disorder of heme biosynthesis inherited in an autosomal recessive fashion. The molecular abnormality responsible for the characteristic defect in uroporphyrinogen III synthase activity was investigated in two patients. For the first patient, complementary DNA was specifically amplified using the polymerase chain reaction and subsequently cloned and sequenced. Data obtained revealed the coexistence of two distinct point mutations: a T to C change in codon 73 (arginine in place of a cysteine) and a C to T change in codon 53 (leucine in place of a proline). The second case was studied by hybridization with allele specific oligonucleotides and was found to be homozygous for the same mutation in codon 53. These are the first mutations to be recognized in the uroporphyrinogen III synthase gene from congenital erythropoietic porphyria patients. PMID- 2331521 TI - Human endothelial cells synthesize, process, and secrete fibronectin molecules bearing an alternatively spliced type III homology (ED1). AB - Cellular fibronectin (Fn) bearing an alternatively spliced extra type III structural repeat (ED1) is normally present at low concentrations in blood plasma. The source of this material remains uncertain. In this study, primary cultures of human umbilical vein endothelial cells (HUVEC) labeled with 35S methionine were observed to synthesize Fn monomers both with and without this segment. Monomers isolated from cell lysates with antibodies to the ED1 sequence comigrated in nonreduced sodium dodecyl sulfate polyacrylamide gel electrophoresis with the slower (designated M1), but not the faster (designated M2), of two major monomeric populations that were recognized by antibodies raised to plasma-derived Fn. The differences between M1 and M2 were not due to glycosylation, since they were also observed between species of Fn monomer purified from cells grown in the presence of tunicamycin. M1 and M2 were both observed to incorporate with a similar rate into dimeric Fn, indicating that Fn monomers with and without the ED1 site can dimerize with similar efficiency. Analysis of reduced samples of Fn isolated from cells with anti-ED1 antibodies indicated the presence of both M1-M1 and M1-M2 dimers. In addition to being incorporated into extracellular matrix, ED1 + Fn was observed to be secreted in soluble form into the medium, potentially reflecting intravascular release of this protein by endothelial cells in vivo. PMID- 2331522 TI - Analyses of thrombocytopenia in idiopathic thrombocytopenic purpura-prone mice by platelet transfer experiments between (NZW x BXSB)F1 and normal mice. AB - Male (NZW x BXSB) F1 (W/B F1) mice, which develop lupus nephritis, myocardial infarction, and thrombocytopenia, showed reduced platelet lifespan (PLS) and increased platelet-associated antibody (PAA) values. There were statistically significant correlations between the increase in PAA values and either the reduction in PLS or the decrease in platelet counts. This and the results of platelet transfer experiments between old male W/B F1 mice and either female W/B F1 or normal BALB/c mice indicate that PAAs on the platelet surface play a crucial role in the destruction of platelets in W/B F1 mice. The mechanism of thrombocytopenia observed here appears similar to that of human idiopathic thrombocytopenic purpura (ITP). Therefore, we think that W/B F1 mice are a potentially useful animal model for investigating the effectiveness and mode of action of therapeutic agents in human ITP, and that they may provide additional information on the basic mechanisms of this autoimmune phenomenon. PMID- 2331523 TI - High prevalence of T-cell receptor V delta 2-(D)-D delta 3 or D delta 1/2-D delta 3 rearrangements in B-precursor acute lymphoblastic leukemias. AB - Rearrangement of the immunoglobulin (Ig) and T-cell receptor (TcR) genes generally has been considered a useful marker of B- and T-cell lineage in lymphoproliferative disorders. However, concomitant rearrangements of Ig and TcR genes have been commonly reported in the most immature lymphoid malignancies, mainly in B-cell precursor acute lymphoblastic leukemia (ALL). To better characterize the nature of this lineage promiscuity, we have analyzed the configuration of the TcR delta locus in 75 B-precursor ALL. The large majority of cases (87%) displayed a rearrangement or deletion at the delta locus. Among the 57 nondeletional rearrangements, two patterns were predominant and both appeared to derive from partial joining: a V delta-(D)-D delta 3 (32/57) and a D delta 1/2 D delta 3 (11/57) type. A single V delta gene (V delta 2) appeared to be involved in the first type of rearrangement. These findings are at variance with T-ALL, where rearrangements 5' to V delta 2 are usually found. It remains to be elucidated whether this incomplete attempt of V delta 2 gene assembly is related to the neoplastic event or represents a physiologic predisposition occurring during early stages of the normal lymphocyte differentiation. PMID- 2331524 TI - Chromosomal abnormalities in untreated patients with non-Hodgkin's lymphoma: associations with histology, clinical characteristics, and treatment outcome. The Nebraska Lymphoma Study Group. AB - We describe the chromosomal abnormalities found in 104 previously untreated patients with non-Hodgkin's lymphoma (NHL) and the correlations of these abnormalities with disease characteristics. The cytogenetic method used was a 24- to 48-hour culture, followed by G-banding. Several significant associations were discovered. A trisomy 3 was correlated with high-grade NHL. In the patients with an immunoblastic NHL, an abnormal chromosome no. 3 or 6 was found significantly more frequently. As previously described, a t(14;18) was significantly correlated with a follicular growth pattern. Abnormalities on chromosome no. 17 were correlated with a diffuse histology and a shorter survival. A shorter survival was also correlated with a +5, +6, +18, all abnormalities on chromosome no. 5, or involvement of breakpoint 14q11-12. In a multivariate analysis, these chromosomal abnormalities appeared to be independent prognostic factors and correlated with survival more strongly than any traditional prognostic variable. Patients with a t(11;14)(q13;q32) had an elevated lactate dehydrogenase (LDH). Skin infiltration was correlated with abnormalities on 2p. Abnormalities involving breakpoints 6q11 16 were correlated with B symptoms. Patients with abnormalities involving breakpoints 3q21-25 and 13q21-24 had more frequent bulky disease. The correlations of certain clinical findings with specific chromosomal abnormalities might help unveil the pathogenetic mechanisms of NHL and tailor treatment regimens. PMID- 2331525 TI - Blood kinetics, tissue distribution, and radioimaging of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody CLL2 in mice transplanted with cCLLa-bearing human leukemia cells. AB - The blood kinetics and biodistribution of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody (MoAb) CLL2 were assessed in mice bearing cCLLa+ tumors. The cCLLa is a 69-Kd glycoprotein antigen expressed selectively by malignant B cells in human CLL, hairy cell leukemia (HCL), and prolymphocytic leukemia. Immunoreactive 125I-CLL2 (5 micrograms/mouse, specific activity 4.3 microCi/micrograms) was injected intravenously in mice bearing HCL-derived EH xenografts, and blood kinetics and biodistribution were ascertained up to 16 days postinjection. Radioimages were also obtained up to 72 hours after injecting 10 micrograms/mouse (specific activity 50.1 microCi/micrograms) of 125I-CLL2. Distinct 125I-CLL2 blood kinetics were observed in EH engrafted compared with tumor-free mice including: a longer 125I-CLL2 T 1/2 (153 hours v 72 hours), and a considerably greater blood clearance (173 mg/h v 54.7 mg/h) with biexponential rather than monoexponential configuration; and a greater volume of antibody distribution (31,483 mg v 5,729 mg). These data suggest more rapid tissue uptake by grafted tumours. Preferential 125I-CLL2 uptake by EH tumours relative to normal tissues was observed beginning 24 hours postinjection (mean ratio, 4.2) with average peak tumor 125I-CLL2 levels of 428.7 pg/mg. 125I-CLL2 uptake selectivity by EH tumor cells was also supported by: (1) negligible 125I-CLL2 uptake by cCLLa- Molt-4 xenografts (average 29.1 pg/mg 24 hours postinjection); (2) background uptake of cCLLa-irrelevant MoAb 131I-LEU1 by CD5- EH xenografts (average 31.4 pg/mg 48 hours postinjection); and (3) by scintigraphy. The EH xenograft mouse model might be useful to ascertain preclinically the anti-tumor effect of anti-cCLLa MoAbs and of their conjugated derivatives. PMID- 2331527 TI - Therapy of chronic idiopathic thrombocytopenic purpura in adults. PMID- 2331526 TI - Serum transferrin receptor: a quantitative measure of tissue iron deficiency. AB - This study was undertaken to evaluate the role of serum transferrin receptor measurements in the assessment of iron status. Repeated phlebotomies were performed in 14 normal volunteer subjects to obtain varying degrees of iron deficiency. Serial measurements of serum iron, total iron-binding capacity, mean cell volume (MCV), free erythrocyte protoporphyrin (FEP), red cell mean index, serum ferritin, and serum transferrin receptor were performed throughout the phlebotomy program. There was no change in receptor levels during the phase of storage iron depletion. When the serum ferritin level reached subnormal values there was an increase in serum receptor levels, which continued throughout the phlebotomy program. Functional iron deficiency was defined as a reduction in body iron beyond the point of depleted iron stores. The serum receptor level was a more sensitive and reliable guide to the degree of functional iron deficiency than either the FEP or MCV. Our studies indicate that the serum receptor measurement is of particular value in identifying mild iron deficiency of recent onset. The iron status of a population can be fully assessed by using serum ferritin as a measure of iron stores, serum receptor as a measure of mild tissue iron deficiency, and hemoglobin concentration as a measure of advanced iron deficiency. PMID- 2331528 TI - Interleukin-6 and phospholipase A2 in sepsis. PMID- 2331529 TI - Lymphocyte phenotype after treatment for leukemia. PMID- 2331530 TI - Gas chromatography/electron impact mass spectrometry, fast atom bombardment mass spectrometry, mass-analyzed ion kinetic energy spectroscopy and B/E linked scan analysis of triaryl phosphates and triethylene glycol fatty acid esters. AB - Tris(isopropylphenyl/phenyl) phosphates and triethylene glycol dicaprate/caprylate mixtures of typical industrial compositions have been analyzed by fast atom bombardment (FAB) mass spectrometry, FAB collisional activation (CA) mass-analyzed ion kinetic energy spectroscopy and FAB/electron impact (EI) CA B/E linked scans. Data obtained by these state-of-the-art methodologies are compared qualitatively and semi-quantitatively with those provided by classical gas chromatography (GC)/EI MS. To identify the plasticizers in cases of suspected contamination, GC/EI MS still appears to be the method of choice whenever ultimate sensitivity and specificity are needed. In cases where these requirements are less demanding, FAB mass spectrometry and FAB tandem mass spectrometry may be sufficient and more convenient. PMID- 2331531 TI - Enzymatic cleavage directly on the probe tip for mass spectrometric identification of peptides. AB - Fast atom bombardment mass spectrometry was used in direct combination with enzymatic cleavages by endopeptidases for the identification of peptides derived from recombinant proteins. By this fast and simple reaction on the probe tip, the enzymes produced a mixture of smaller peptides. Molecular weights were calculated in advance and used for verification of the amino acid sequence of the original peptide as well as for partial structure determinations. Since the enzymatic reaction took place directly on the probe tip, sample material and time was saved. This technique may be applied especially in such cases where mass spectrometry alone does not give sufficient information and if the mass range of the instrument is limited, e.g. to 2000 daltons. PMID- 2331532 TI - Bacterial phospholipid analysis by fast atom bombardment mass spectrometry. AB - The structural analysis of naturally occurring bacterial phospholipids in mixtures by fast atom bombardment (FAB) mass spectrometry are reported. The bacterial strains examined included several genera of actinomycetes, two strains of Escherichia coli, and one strain each of Proteus mirabilis and Pseudomonas aeruginosa. FAB mass spectrometry proved to be a useful tool for the structural identification of phospholipids in mixtures and provided stable pseudo-molecular ions and characteristic fragment ions which permitted the identification of phosphatidylethanolamine and phosphatidyl choline. Information regarding the chain length of the fatty acids, their degree of unsaturation in the chains and the presence of hydroxyl groups was also obtained. The results obtained by FAB mass spectrometry were supported by high-resolution mass spectral data, tandem mass spectrometric studies and FAB mass spectrometry of components which had been separated and partially purified by thin-layer chromatography. Each organism displayed a highly characteristic phospholipid profile suggesting the possible use of FAB mass spectrometry as a method for rapid bacterial detection and identification. PMID- 2331533 TI - Mass spectrometric identification of 2-hydroxydodecanedioic acid and its homologues in urine from patients with hopantenate therapy during clinical episode. AB - Urine from patients with calcium-4-(2,4-dihydroxy-3,3-dimethylbutyramido) butyrate hemihydrate (hopantenate) therapy during episodes of Reye's-like syndrome was found to contain a number of unusual dicarboxylic acids in high concentrations; odd- and even-numbered medium-chain dicarboxylic acids, alpha hydroxydicarboxylic acids and beta-hydroxydicarboxylic acids. The abnormal excretion of dicarboxylic acids, alpha- and beta-hydroxydicarboxylic acids disappeared after discontinuance of hopantenate therapy. Besides the excretion of 2-hydroxydecandedioic acid, which has been previously described in Zellweger syndrome or neonatal adrenoleukodystrophy, a series of alpha-hydroxydicarboxylic acids was detected and identified. In this paper, we have characterized some new compounds by gas chromatography/mass spectrometry: 2-hydroxydodecanedioic acid, 2 hydroxydodecenedioic acid, 2-hydroxytetradecanedioic acid, 2 hydroxytetradecenedioic acid and 2-hydroxyoctanedioic acid. PMID- 2331534 TI - Baseline measurements for stable isotope studies: an alternative to biopsy. AB - Studies of protein metabolism with stable isotopes require determination of the 'natural' isotopic enrichment in tissues. This has previously been determined by taking a pre-test muscle biopsy or by using the isotopic enrichment of a separate control group of subjects. In this study we have measured and compared the 'natural' 13C enrichment of leucine in plasma protein and muscle protein in 14 subjects. The mean enrichment of leucine (delta 13CPDB) in muscle protein, 26.627, was not significantly different from that in plasma protein, -27.152. The data indicate that the 13C enrichment of leucine in plasma protein reflects that of muscle protein and provides an attractive alternative to an additional muscle biopsy in studies of protein metabolism with stable isotopes. PMID- 2331535 TI - Analysis of rat urine for metabolites of pyrilamine via high-performance liquid chromatography/thermospray mass spectrometry and tandem mass spectrometry. AB - Combined high-performance liquid chromatography/thermospray mass spectrometry (HPLC/TSMS) and HPLC/thermospray tandem mass spectrometry (HPLC/TSMS/MS) were utilized for the analysis of rat urine for metabolites of pyrilamine. The sample was analyzed via HPLC/TSMS/MS in the parent ion mode in order to identify potential metabolites of pyrilamine. Then HPLC/TSMS/MS analysis in the daughter ion mode was performed to provide additional analytical selectivity plus enhanced fragmentation of suspected protonated molecules. By this methodology, suspected pyrilamine metabolites were confirmed to be in the sample and several novel metabolites of pyrilamine were discovered and tentatively identified. PMID- 2331536 TI - Allogeneic bone marrow transplantation for leukemia in Europe: regional differences. Report from the Leukemia Working party of the European Group for Bone Marrow Transplantation. AB - The results of 1904 allogeneic HLA identical sibling donor bone marrow transplants performed in 52 European centers between 1979 and 1986 and reported to the EBMT leukemia registry were analysed by geographical location of the transplant. Patients were grouped into six regions: United Kingdom, Nordic Group, Benelux, France, Central Europe and Southern Europe. There were significant differences between these regions with respect to patient population and outcome. The relative proportion of the three major disease categories, stage and subtype of the diseases, graft-versus-host disease prevention methods, donor recipient sex combinations, age of the patient, year of the transplant and the time intervals from diagnosis to transplant, from diagnosis to first complete remission for acute leukemia and the time from first complete remission to the transplant varied from region to region. The analysis of outcome parameters showed a significant difference in relapse incidence from region to region. This influence of region was confirmed in a multivariate analysis and was independent of the other factors known to affect outcome. Leukemia-free survival and transplant-related mortality were not different. The reasons for these differences could not be explained by the data in the registry. We conclude that regional factors must be considered when bone marrow transplant data are compared and we postulate that pretransplant factors probably affect outcome more than was previously realized. PMID- 2331537 TI - Radionuclide ejection fractions in the evaluation of patients being considered for bone marrow transplantation: risk for cardiac toxicity. AB - One hundred thirty-six patients underwent radionuclide ventriculography as part of an evaluation prior to bone marrow transplantation. One hundred twenty-six who were considered suitable transplant candidates began conditioning chemotherapy or chemoradiotherapy and were retrospectively evaluated for development of cardiac toxicity. The cumulative pretransplant anthracycline dose in patients who began the conditioning regimen was not a significant predictor for decreased pretransplant ejection fraction (EF) or severe cardiac toxicity following transplantation. Fourteen patients (10%) had EFs less than 50%. Of these, 10 began the preparative regimen and two (20%) experienced grade III or IV cardiac toxicity (95% confidence interval (CI) 2.5-56%) versus five of 116 patients (4%; CI 1.4-9.8%) with EFs greater than or equal to 50% (p = 0.096). The incidence of grade III or IV cardiac toxicity among patients with any history of cardiac dysfunction or with an abnormal physical examination prior to transplant was 9% (two of 22) versus 5% among the remaining patients (five of 104) (p = 0.605). Though transplant-related cardiac toxicity may be more common in patients with mildly reduced EFs, the small number of patients with reduced EFs referred for transplant does not warrant the routine pretransplant screening of all patients with radionuclide ventriculography. PMID- 2331538 TI - Growth failure and growth hormone deficiency in children after bone marrow transplantation for leukemia. AB - Eleven patients between the ages of 6 and 18 years who had been treated for acute leukemia were investigated for growth and growth hormone (GH) secretion. All had undergone bone marrow transplantation (BMT) between 0.7 and 5.1 (median 2.0) years previously. Preparation of patients for BMT had included high-dose cyclophosphamide and total body irradiation. In the eight patients at risk of growth failure, the relative height decreased 0.5-2.5 SD units (median 1.0) during the follow-up period. Eight patients secreted subnormal amounts of GH as studied by measuring spontaneous pulsatile GH secretion overnight. The maximal nocturnal GH peak varied between 3.3 and 28.3 micrograms/l (median 9.3). The mean nocturnal GH concentration varied from 1.2 to 8.3 micrograms/l (median 2.3) and depended on the length of the follow-up period. We conclude that deficient GH secretion is one reason for poor growth after BMT. A good growth response to GH substitution would support the role of GH deficiency in the observed growth retardation after BMT. PMID- 2331539 TI - Bone marrow transplantation following busulfan and cyclophosphamide for acute myelogenous leukemia. AB - Twenty-five consecutive patients with acute myelogenous leukemia (AML) underwent 26 allogeneic bone marrow transplants at Hahnemann University Hospital. Marrow ablation for all patients consisted of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BUCY2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methylprednisolone. Seventeen transplants were performed during first remission and the rest during subsequent remission or relapse. All patients engrafted and all but one achieved a complete remission (CR) following a short period of aplasia. Twenty-two of 25 patients are alive. All 17 patients with AML transplanted in first CR are alive and 15 of these patients are in sustained hematologic remission with an estimated 2-year disease free survival of 85%. The estimated 2-year disease free survival is 70% for all patients followed for a median of 622 days (range 134-1533). Acute GVHD of grades 2-4 occurred in 23% of these patients. Toxicities of the regimen including interstitial pneumonitis, veno-occlusive disease (VOD) and hemorrhagic cystitis were minimal. There were no treatment related deaths. These results demonstrate that BUCY2 should be considered as a preparative regimen for allogeneic bone marrow transplantation for patients with AML in first remission. PMID- 2331540 TI - The use of locus-specific minisatellite probes to check engraftment following allogeneic bone marrow transplantation for severe combined immunodeficiency disease. AB - The graft status of 14 patients, 13 of whom had received an allogeneic bone marrow transplant (BMT) for severe combined immunodeficiency disease (SCID) and one patient with SCID in whom intrauterine maternal engraftment was suspected, was examined using bone marrow or peripheral blood DNA and a combination of locus specific minisatellite probes for the sex-matched and locus-specific and a Y specific probe for the sex-mismatched patients. The sensitivity of the assay systems was such that less than 0.1% recipient DNA was detectable in a background of donor DNA. Graft status could be satisfactorily documented by 2.5 weeks post transplant and in one case was of particular value as immunological parameters were misleading. In the six long-term survivors of allogeneic BMT for SCID, the use of the locus-specific probes showed total donor lymphoid and myeloid haemopoietic engraftment in five cases and mixed host/donor populations in one case. The diagnosis in approximately 10% of cases of SCID may prove difficult due to engraftment of the fetus by maternal cells. Diagnosis may be facilitated by the use of the locus specific minisatellite probes and indeed we found specific evidence for such maternal engraftment in one patient at presentation. The combination of these probes together with a Y specific probe thus provides a rapid and accurate method of assessing graft take following allogeneic BMT for SCID. The simple pattern of inheritance obtained and the high level of sensitivity of detection of low numbers of allogeneic cells make the techniques amenable for use in any routine DNA diagnostic laboratory. PMID- 2331541 TI - Use of an immunoglobulin preparation enriched for IgA to treat recurrent sinopulmonary infections in a patient with chronic GVHD. PMID- 2331542 TI - Psychological sequelae of closed head injury: time to redress the imbalance. PMID- 2331543 TI - The structure of head-injured patients' neurobehavioural complaints: a preliminary study. AB - Psychological functioning in 55 severely head-injured individuals was investigated in order to extend findings on the long-term nature of psychological sequelae after closed head injury. Results showed that head-injured subjects reported numerous psychological deficits many years post-injury, were psychologically distressed by their own report (Brief Symptom Inventory) and that of care-giving relatives (Katz Adjustment Scale--Relatives Version), and also exhibited a different pattern of coping from that of a normative group. A three factor model of residual psychological complaints that contained a 'General Complaints' factor, a 'Somatization' factor and a 'Severity' factor was identified; this showed some similarity to a model proposed by van Zomeren and van den Burg (1985). Results indicate support for the 'coping hypothesis' of post injury psychological deficits, although effects consistent with a 'gradations of severity' hypothesis were also present. PMID- 2331544 TI - Features of chronic subdural haematoma developed from definitely identified acute subdural haematoma. AB - Follow-up results for 13 cases of acute subdural haematoma, which were identified by CT scan within two days of head injury and treated conservatively, were classified into two groups: In the first group of seven cases the acute subdural haematoma disappeared spontaneously within two weeks; in the second group the other six cases revealed clinical signs and CT scan findings which were identical to chronic subdural haematoma and underwent surgery within three weeks after the head injury. This group showed low ICP signs, such as the chronic stage of cerebral thrombosis, atrophic brain or subdural fluid collection with acute subdural haematoma at the initial CT scan, and most of these cases had only minor head injury. Common features of the operative findings in this second group, in which chronic subdural haematoma developed, included the identification of an external haematoma capsule based on the fibrin layer and granulation tissue beneath the dura. Also, fluid type haematoma was present under these structures, but no inner membrane of the haematoma could be identified other than the non transparent white arachnoid membrane. Our results indicate the importance of a low ICP in determining whether or not acute subdural haematoma progresses to chronic subdural haematoma. PMID- 2331545 TI - Polytrauma associated with traumatic brain injury: incidence, nature and impact on rehabilitation outcome. AB - The rehabilitation outcome of patients with severe traumatic brain injury (TBI) is well documented and is highly correlated to the neurobehavioural sequelae of CNS damage. However, many of these patients suffer from polytrauma involving systems other than the CNS and to systems involved in acquisition of external information. In the present series of 328 patients with severe TBI, 58% had associated trauma, mostly in the skeletal system. The presence of one single associated trauma had no additional effect on rehabilitation as evaluated by actual work placement. In contrast, multiple lesions were liked with a less favourable outcome, probably due to a greater severity of the initial CNS damage. Disturbances in the various information-acquiring systems (e.g. disturbances in eye movements, visual field defects and severe bilateral auditory deficits) were associated with poor outcome. Presence of peri-articular new bone formation and communicating hydrocephalus, usually associated with prolonged periods of unconsciousness, indicated a poor rehabilitation outcome as well. PMID- 2331546 TI - Intensity of rehabilitation and length of stay. AB - This study investigated the effects of different levels of brain injury rehabilitation intensity on length of stay in two hospital-based coma and acute rehabilitation populations. In two hospitals, in separate areas of the USA, rehabilitation intensity was increased from 5 h per day to 8 h per day, 7 days per week. Patients were studied retrospectively both before and after the change in intensity. There were no significant differences among subjects in age, education, time since injury or level of functioning on admission either across hospitals or from pre- to post-change-in-intensity. Results show that the length of stay significantly decreased 31% for both coma and acute groups in both hospitals. Implications of these findings for clinical treatment and social policy are discussed. PMID- 2331547 TI - Managing hypersexual disorders in brain-injured clients. AB - Three case studies involving hypersexuality in brain-injured clients are illustrated. Two cases involved the inappropriate touching of the opposite sex, and the third case involved exhibitionism. In one case of touching, feedback was used to decrease inappropriate touching. In the other case of touching, scheduled massage was used to shift stimulus control to an appropriate setting. In the case of exhibitionism, a combination of self-monitoring, private self-stimulation and dating-skills training were used to suppress the behaviour. PMID- 2331548 TI - Effects of mild, moderate and severe closed head injury on long-term vocational status. AB - Survival from significant closed head injury (CHI) is frequently associated with cognitive defects, physical impairment, personality change, interpersonal difficulty and, in general, some degree of social dependence. Here we report a multidimensional assessment of quality of life of a sample of 131 male head injury patients suffering a range of severities of insult with specific emphasis on vocational outcome. Of those patients who sustained a severe injury and were employed full-time prior to the CHI, only 55% were able to return to this level of employment. No differences were found between the moderate and severe groups in pre- or post-CHI occupational status, as measured by the Blishen (1967) quantitative social economic index, although both groups declined from pre- to post-CHI. Lower post-CHI occupational status was associated with lower GCS on admission and longer lengths of post-traumatic amnesia, with patient self-report of physical, cognitive and psychosocial difficulties, including spousal reports of confusion, belligerance, verbal expansiveness and the decreased ability to perform socially-expected activities. Stepwise multiple regression analysis accounted for 38% of variance in post-injury vocational status, with lower pre injury vocational status, greater age, high physical and psychological difficulties and lower admission Glasgow Coma Scale score variables forming the regression equation. Implications are discussed in terms of rehabilitation issues, including vocational programming and planning. PMID- 2331549 TI - The effectiveness of coma arousal intervention. AB - Thirty-one patients who were in coma or persistent vegetative state two weeks after sustaining a severe head injury were entered into a coma arousal programme. The coma arousal protocol called for a sequence of vigorous multisensory stimulations to be applied to the patient by a relative for up to eight hours a day for seven days a week. An independent study team monitored two patient outcomes, the time taken to obey a simple command on two consecutive occasions 24 hours apart and patients' score on the Glasgow Outcome Scale 10-12 months post injury. Outcomes were compared with an historical reference group chosen from the literature, consisting of 135 similarly classified patients. Differences between the pilot study and the reference group patients on initial characteristics suggested that the pilot study patients might have the more favourable outcomes, independent of treatment effect. The sample size was sufficient to detect a 40% improvement in recovery rate. No significant improvements were noted in either the time to obey a simple command (p greater than 0.2) or in the Glasgow Outcome Scale (p greater than 0.25), although the observed difference in the latter group was 11% in favour of the pilot study patients. This study was unable to find any evidence that coma arousal, for all its arduous patient contact, had a markedly better outcome compared with conventional treatment. PMID- 2331550 TI - Treating urinary incontinence in a head-injured adult. AB - The purpose of this study was to determine the effects of four behavioural procedures in helping a head-injured adult to control diurnal and nocturnal enuresis. A multiple baseline, single subject research design was utilized to test the effectiveness of those procedures. Data were collected for a period of seven months, including four months of baseline and intervention, and three months of follow-up. Results showed that the frequency of urinary incidents was reduced to zero at the end of the treatment and follow-up periods. Implications of the research data for future studies about urinary incontinence in head injured patients are discussed. PMID- 2331552 TI - Epidemiologic status of drug abuse in Mexico. AB - Abuse of alcoholic beverages and tobacco appear to constitute priority public health problems in Mexico, while abuse of other drugs is sufficiently widespread to justify concern. More specifically, a recent national survey (11) found that over 10% of the male subjects 18 to 65 years old met established international criteria for alcohol dependence, while about a quarter of those surveyed were active smokers. A total of 4.3% said they had used one or more drugs other than tobacco or alcohol at some time in their lives. PMID- 2331551 TI - Effect of clonidine on post-traumatic memory deficits. PMID- 2331553 TI - Consumption of dependence-producing substances in Colombia. AB - A survey examining the use of six dependence-producing substances (alcohol, tobacco, tranquilizers, marijuana, coca paste or "basuca," and cocaine) was conducted in Colombia in 1987. The survey population consisted of 2,800 urban residents in four cities (Barranquilla, Bogota, Cali, and Medellin) between the ages of 12 and 64. The results indicated that substantially more men than women were using all the substances involved except tranquilizers, that high proportions of study subjects used alcohol and tobacco, that 8.1% of the study subjects could be considered alcoholics, and that another 7.3% were at risk of becoming alcoholics. User prevalences of the three illegal substances (marijuana, basuca, and cocaine) were much lower, and the prevalence of marijuana users exceeded that of the other two drugs combined. However, 1% of the male study subjects reported using basuca within the past year. The high prevalence of basuca use has important public health implications, because the drug typically does great harm to its users within a short period of time. PMID- 2331554 TI - Drug use in Ontario, Canada. AB - Two long-term surveys of drug use have been carried out in Ontario, Canada--one involving middle- and high-school students, and the other adults in the general population. These studies revealed that use of tobacco and alcohol is common and that cannabis is the most widely used illicit drug by both the students and adults (15.9% and 9.5%, respectively, in 1987). Use of other illicit drugs is much less common. The trend data from 1977 to 1987 show a decrease in all drug use among students and a basically stable pattern among adults, with the exception of an upward trend in cocaine use. A study of adult cocaine users in the community found that half had experienced intense cravings for cocaine and other adverse effects. Demographic information was also gathered that made it possible to outline the most common characteristics of cannabis and cocaine users. PMID- 2331555 TI - Drug abuse in Costa Rica: a review of several studies. AB - This article provides a review of drug use surveys conducted by Costa Rica's Institute on Alcoholism and Drug Dependence during the years 1983-1987. These studies dealt with a wide range of subjects--residents of marginal neighborhoods, juvenile male and adult female detainees, and high school students--as well as with the general population. Overall, the studies indicated that the most commonly used illicit drug was marijuana, that the bulk of the drug users (excluding alcohol and tobacco users) were young males, that relevant levels of cocaine use were starting to occur, and that the country's general drug abuse picture poses a problem in need of immediate attention. PMID- 2331556 TI - Prevalence of the improper use of alcohol, tobacco, and drugs in the Ecuadorian population. AB - An epidemiologic investigation was conducted in 1988 to measure prevalences of the improper use of alcohol, tobacco, and drugs in the Ecuadorian population. This research was based on a structured interview survey of 6,000 individuals representative of the country's entire population between the ages of 10 and 65. The relative frequency of the various common forms of consumption of these substances was also investigated. Overall, the substances used by the highest percentages of study subjects at least once in their lives were alcohol (by 75%) and tobacco (by 54%). Lesser percentages had used medically prescribed psychotropic drugs (for example, 16% reported using tranquilizers at least once). The percentages using the same drugs illegally, without prescription, were lower (for example, 4% in the case of tranquilizers), and the percentages reporting use of outlawed drugs were also small (the respective percentages reporting use of marijuana, inhalants, native plant drugs, cocaine, and cocaine base were 4%, 2%, 1%, 1%, and 1%). The study also found that the prevalences of addiction to substances other than alcohol and tobacco were relatively low, ranging from 0.8% for tranquilizers taken without prescription to 0.01% for cocaine. PMID- 2331557 TI - Comparison of alcohol, tobacco, and illicit drug use among students and delinquents in the Bahamas. AB - Surveys of drug use were conducted among 4,767 junior and senior high school students in 1987 and 74 incarcerated delinquents in 1988 in the Bahamas. It was found that the majority of both groups reported having drunk alcohol, and substantial proportions had also smoked tobacco, although over twice as many delinquents as students had smoked. However, use of illicit drugs was far more common among delinquents, at seven times the student rate for marijuana and six times their rate for cocaine. Many social and demographic similarities were found among users in both groups, who were likely to be males who had trouble in school or did not attend school, were not religiously active, and came from families where drugs were used or sold. Over one-third of the delinquents had sold drugs, but almost half (44%) of the delinquents and 25% of the students said they would use or sell marijuana or cocaine if they had it. The results of the studies point to the need for increased drug education in the Bahamas and for efforts involving schools, churches, parents, the media, and Government. PMID- 2331558 TI - Development of a System for Registry of Information on Drug use in Mexico. AB - Mexico's need for uniform information about drug abuse led to creation of an information collection system in 1986. This system, known as the System for Registry of Information on Drugs (SRID), currently covers the Mexico City metropolitan area. Plans call for it to be expanded in two phases--so as to provide coverage first of the states near the U.S. border and those with substantial tourism, and then to cover the nation as a whole. This article describes the data collection procedures used and the results of the four SRID assessments conducted in the Mexico City area from mid-1986 through mid-1988. These results indicate there were about nine male drug abusers in this period for every female; that drug use typically began young; that the drugs most commonly abused were marijuana, inhalants, alcohol, tobacco, and tranquilizers; that cocaine use was limited but apparently increasing; and that most of the drug abusers interviewed had not completed secondary school, were not in school at the time interviewed, and had relatively low socioeconomic status. PMID- 2331559 TI - Epidemiology of drug abuse in the United States: a summary of methods and findings. AB - Epidemiology has recently been used to effectively track and analyze drug abuse patterns. This article generally describes methods used in the United States for estimating and monitoring drug abuse. It outlines the advantages and limitations of such data sources as surveys, indicators, and ethnography, and briefly explores the work and utility of local, national, and international drug surveillance networks. In addition, it describes national and local patterns of heroin, cocaine, and marijuana abuse. PMID- 2331560 TI - Obtaining epidemiologic information on the improper use of psychoactive substances: strategies applied in Argentina. AB - In seeking epidemiologic information on the improper use of psychoactive substances it makes good sense to take advantage of available institutional resources, especially in situations where more usual research resources are in short supply or altogether lacking. This article describes several studies that availed themselves of institutional resources in Argentina for the purpose of obtaining this type of information. One of these was carried out by personnel at several rehabilitation centers dealing with problems related to improper use of psychoactive substances; another obtained information from physicians and auxiliary personnel providing emergency treatment at three general hospitals; and another used the facilities of labor organizations to investigate workers' problems. All in all, these projects show how innovative approaches can help to obtain key substance abuse information; they could also serve as worthwhile models for those interested in carrying out similar work with limited resources. PMID- 2331561 TI - Validity of the Addiction Severity Index (adapted version) in a Costa Rican population group. AB - Until recently, no adapted and validated instrument was available for assessing the alcohol and drug problems of individuals in Costa Rica. This article reports the results of a study performed by Costa Rica's Institute on Alcoholism and Drug Dependence in order to test an adapted version of one such instrument, the Addiction Severity Index (ASI), in a Costa Rican setting. The instrument was used to interview 100 male subjects 18 to 64 years old (51 with diagnosed alcohol or drug problems and 49 controls). In general, the subjects with previously diagnosed alcohol or drug problems were assigned substantially higher scores. More specifically, statistical analysis indicated highly significant correlations (p less than 0.001) between the type of subject (test subject or control) and the likelihood that noteworthy problems would be found in the areas of alcohol use, family/social relations, work/finances, and psychological status. Overall, the study demonstrated that the instrument was capable of distinguishing between the affected and unaffected populations, and also of gauging the severity of the problems involved and the patients' treatment needs. PMID- 2331562 TI - Alcoholism and other substance abuse: preventive programs in Santiago, Chile. AB - This paper describes efforts that began in the 1970s to prevent alcohol and drug abuse among adolescents in Chile and discusses current health promotion programs that focus on prevention of health-endangering behaviors. Adolescent substance abuse has been found to be strongly correlated with familial dysfunction and parental drug abuse as well as with certain behavioral characteristics. Therefore, prevention activities should target high-risk children as identified by screening instruments. Interventions should be carried out at the individual, school, family, community, and societal levels. It is important to analyze the feasibility of implementing prevention activities and to systematically evaluate their effectiveness. PMID- 2331563 TI - Epidemiologic report on the use and abuse of psychoactive substances in 16 countries of Latin America and the Caribbean. PMID- 2331564 TI - The effect of two lipophilic gamma-aminobutyric acid uptake blockers in CA1 of the rat hippocampal slice. AB - 1. Drugs that increase inhibitory synaptic transmission in the central nervous system may be valuable tools in the treatment of seizures. Theoretically, substances that block the uptake of inhibitory transmitters such as gamma aminobutyric acid (GABA) into intracellular compartments should also increase inhibition and therefore have potential value as antiepileptic drugs. However, most of these substances penetrate the blood-brain barrier poorly and have therefore until now had limited value. NO-05-0328 and NO-05-0329 are two new lipophilic GABA uptake inhibitors that readily enter the CNS from the blood. 2. We have investigated the effect of these two uptake inhibitors on the responses to exogenous GABA and on GABA-mediated inhibitory synaptic potentials in pyramidal neurones of the CA1 region in the rat hippocampal slice. 3. We found that both drugs increased the amplitude and duration of responses to exogenous GABA. Furthermore, the inhibitory synaptic potentials increased in amplitude. This increase was seen in both early and late phases of the synaptic potentials. We conclude that NO-05-0328 and NO-05-0329, at least in vitro, are more effective than older GABA uptake inhibitors such as nipecotic acid and they therefore deserve consideration for clinical use. PMID- 2331565 TI - Chronic diazepam treatment in rats causes long-lasting changes in central [3H]-5 hydroxytryptamine and [14C]-gamma-aminobutyric acid release. AB - The effects of chronic diazepam administration to rats on the central release of [3H]-5-hydroxytryptamine ([3H]-5-HT) and [14C]-gamma-aminobutyric acid ([14C] GABA, ex vivo) were examined. Chronic (5 and 21 days) administration of diazepam (4 mg kg-1 i.p. daily for 21 days) reduced the K-evoked (20 mM KCl) release of [3H]-5-HT from frontal cortex by approximately 50%. Remarkably, this decrease was still present 1 week after diazepam withdrawal. Chronic diazepam treatment did not significantly affect hippocampal [3H]-5-HT release but after 21 days the K evoked release of [14C]-GABA was more than doubled and remained elevated 30 h after withdrawal; it returned to control levels after 1 week, and decreased below control levels after 2 weeks. This study indicates that chronic diazepam treatment produces striking changes in transmitter release in rats that persist long after treatment has ceased. PMID- 2331566 TI - The combined electrophysiological effects of lignocaine and sotalol in canine isolated cardiac Purkinje fibres are rate-dependent. AB - 1. The frequency-dependent electrophysiological effects of lignocaine, sotalol, and their combination were studied in dog isolated cardiac Purkinje fibres, both at various constant rates of stimulation and following abrupt changes in pacing cycle length. 2. The combined effect of 18 microM lignocaine and 30 microM sotalol selectively lengthened duration of premature action potentials evoked at a diastolic interval of 40 ms (from 172.2 +/- 5.4 to 201.7 +/- 4.9 ms, n = 6, P less than 0.01) without significantly changing the durations of action potentials evoked at the basic cycle length of 500 ms (259.1 +/- 7.7 vs 251.9 +/- 3.9 ms, n = 11). 3. The combination of lignocaine with sotalol, like lignocaine alone, displayed a use-dependent depression of Vmax and revealed a slow component for a recovery of Vmax (tau = 173.5 +/- 16.0 ms, n = 5). 4. The kinetics for restitution of action potential duration were also slowed by the combination of the two dwo drugs (tau f = 173.6 +/- 16.7, before, vs 268.5 +/- 8.5 ms, after; n = 5, P less than 0.01), while the maximum action potential duration attained in this relation was not increased as it was by sotalol alone. 5. Lignocaine, therefore, appeared to inhibit the sotalol-induced lengthening of action potential duration at slow pacing rates and at long diastolic intervals. The combination of lignocaine with sotalol also completely abolished the occurrence of sotalol-induced early after depolarizations. 6. Finally, sotalol alone moderately increased the range of premature action potential durations, while the combination of the two drugs significantly decreased this parameter. 7. These findings indicate that the combination of lignocaine with sotalol may provide important, and unique, beneficial electrophysiological alterations that might be expected to provide enhanced antiarrhythmic efficacy in patients. PMID- 2331567 TI - Renal selective N-acetyl-gamma-glutamyl prodrugs: a study on the mechanism of activation of the renal vasodilator prodrug CGP 22979. AB - 1. In this study the processes underlying the renal selectivity of the vasodilator prodrug CGP 22979 (N-acetyl-L-glutamic acid-N-[N2-(5-n-butyl-2 pyridyl) hydrazide]) were studied in rats. 2. The active drug CGP 18137 (2 hydrazino-5-n-butyl pyridine) selectively accumulated in the renal tissue following administration of the prodrug. 3. The kidney concentrations of active drug following prodrug administration were significantly lower than control values when either buthionine sulphoximine, glutathione or probenecid was coadministered (29 +/- 11; 33 +/- 14 and 61 +/- 20% of control values, respectively). Inhibition of gamma-glutamyl transpeptidase by AT-125 did not cause a significant decrease of renal CGP 18137 levels. 4. In order to correlate tissue drug concentrations with pharmacological effect, the renal haemodynamic responses to CGP 22979 were measured and the effect of buthionine sulphoximine, glutathione and AT-125 on these responses evaluated. All three of the compounds attenuated the renal response to the prodrug: an approximately 50% lesser decrease in renal resistance was found. The compounds had no effect on the haemodynamic actions of CGP 18137 itself. 5. In vitro, it was found that kidney cytosol was able to convert the prodrug, whereas microsomes were not, unless acylase was added. 6. The results indicate that, upon prodrug administration, gamma-glutamyl transpeptidase is not involved in the renal accumulation of CGP 18137 but is partly responsible for the renal haemodynamic responses to CGP 22979. Active transport of the prodrug into the tubular cells appears to be the major reason for the renal selectivity. A model is proposed for the renal action of CGP 22979, in which the important parts are the uptake of the prodrug via a transport system followed by an intracellular conversion to the active drug. PMID- 2331568 TI - Action of an irreversible acetylcholine esterase inhibitor, soman, on muscarinic hyperpolarization in cat bladder parasympathetic ganglia. AB - 1. Intracellular recording techniques were used to examine the action of an irreversible acetylcholine esterase (AChE) inhibitor, soman, on the hyperpolarizations mediated through muscarinic cholinoceptors in cat bladder parasympathetic neurones. 2. Soman (0.1-10 microM) depressed the amplitude and prolonged the duration of the muscarinic slow inhibitory postsynaptic potential (s-i.p.s.p.) elicited by a preganglionic tetanus (40 Hz for 1 s) in the presence of mecamylamine (20 microM), phentolamine (1 microM) and caffeine (1 mM), in a dose-dependent manner. The effect of soman on the amplitude of the s-i.p.s.p. was partially reversible, while the effect on the duration was irreversible. 3. Soman hyperpolarized the membrane and decreased input resistance, but this effect could not account for soman-induced inhibition of the s-i.p.s.p. 4. Soman depressed the amplitude and prolonged the duration of a muscarinic hyperpolarization induced by pressure application of acetylcholine (ACh) in the presence of mecamylamine, phentolamine and caffeine. The time course of this effect paralleled that on the synaptically-evoked muscarinic s-i.p.s.p. 5. A reversible AChE inhibitor, pyridostigmine (10-100 microM), also depressed the amplitude and prolonged the duration of a muscarinic hyperpolarization induced by either preganglionic stimulation or ACh pressure application. These actions were reversible, and not accompanied by a significant change in membrane potential or input resistance. 6. The inhibitory action of soman (1 microM) on the muscarinic hyperpolarization was prevented by pyridostigmine (10 microM), but not by atropine (1 microM). 7. These results demonstrate that soman prolongs not only the muscarinic hyperpolarization, but also inhibits its amplitude through a postsynaptic action, probably through AChE inhibition, in cat bladder parasympathetic neurones. PMID- 2331569 TI - Differential inhibition by two hetrazepine PAF antagonists of acute inflammation in the mouse. AB - 1. The injection of 100 or 300 micrograms of carrageenin into the mouse paw or pleural cavity produced a delayed inflammatory reaction at 48 h while platelet activating factor (PAF)-induced paw oedema and pleurisy were maximal 30 min after its injection. 2. The PAF antagonist, WEB 2086, failed to inhibit mouse paw oedema and pleurisy induced by PAF, but reduced the first phase of oedema (1-4 h) induced by carrageenin without interfering with the second one (48-72 h). In contrast, another structurally-related PAF antagonist, WEB 2170, inhibited dose dependently both oedema and pleurisy induced by PAF and by carrageenin (48 h). 3. Repeated injections of PAF into the mouse paw or pleural cavity led to significant autodesensitization. The animals desensitized to PAF and injected with carrageenin also displayed a significantly reduced oedema. 4. Our results suggest that PAF may be involved in the inflammatory response to carrageenin in mice. Furthermore, because the different receptor antagonists displayed distinct effects against PAF itself, different sites for in vivo interaction of PAF are available and are species- and drug-dependent. PMID- 2331570 TI - Motor response of the human isolated small intestine and urinary bladder to porcine neuromedin U-8. AB - 1. Porcine neuromedin U-8 produced a concentration (0.3 nM-1 microM)-dependent contraction of the longitudinal muscle of the human isolated ileum, which was unaffected by either atropine (1 microM) or tetrodotoxin (1 microM). 2. By contrast, neuromedin U-8 had only a weak effect on the circular muscle of the human isolated ileum. 3. Neuromedin U-8 also produced a concentration-dependent contraction of mucosa-free muscle strips from the dome of the human isolated urinary bladder, its action being unaffected by either atropine or tetrodotoxin. 4. These findings indicate that neuromedin U-8 exerts a direct contractile effect on smooth muscle of the human intestinal and urinary tract. PMID- 2331571 TI - Agmatine acts as an antagonist of neuronal nicotinic receptors. AB - 1. Tritiated agmatine has been used by others in ion flux methods to measure nicotinic receptor function in neurones. However, as shown here, agmatine blocks nicotinic receptor function in both the chick retina and the rat superior cervical ganglion at high concentrations. 2. In intact chick retina, agmatine 1 mM decreases dimethylphenylpiperazinium (DMPP)-induced depolarizations measured in the optic nerve by approximately 70%, while having little effect on responses induced by glutamate analogues. DMPP dose-response curves are reduced in a manner consistent with a non-competitive effect of agmatine, and agmatine at 1 mM does not prevent binding of 125I-labelled neuronal bungarotoxin, a snake venom neurotoxin that competitively binds and blocks functional nicotinic receptors in chick retinal homogenates. 3. Agmatine (10 mM) substantially blocks both DMPP induced depolarizations of rat superior cervical ganglion and synaptic transmission through the ganglion. Others have established that [3H]-agmatine will pass through nicotinic receptor channels in the rat ganglion. These data suggest that agmatine acts both as a cation and as a weak channel blocker at neuronal nicotinic receptors. PMID- 2331572 TI - Receptors mediating the effects of 5-hydroxytryptamine on the tracheal vasculature and smooth muscle of sheep. AB - 1. The effects of 5-hydroxytryptamine (5-HT) and the selective 5-HT3 receptor agonist 2-methyl-5-HT were examined on the tracheal vasculature in anaesthetised, paralysed and artificially ventilated sheep. The cranial tracheal arteries were perfused with blood at constant flow and perfusion pressure was measured. 5-HT and 2-methyl-5-HT were injected into the arterial perfusate. Changes in tracheal smooth muscle tone were also measured. 2. 5-HT contracted the tracheal smooth muscle. This contraction was not affected by the 5-HT2 receptor antagonist ketanserin, but was blocked by the combined '5-HT1-like' and 5-HT2 receptor antagonist methysergide. 2-methyl-5-HT had no effect on the tracheal smooth muscle. 3. 5-HT had a complex action on the tracheal vasculature producing either a biphasic change (vasoconstriction followed by dilatation) or just a constriction. 2-methyl-5-HT had a weak vasoconstrictor effect. 4. The vasoconstrictions produced by 5-HT and 2-methyl-5-HT were blocked by ketanserin. The vasodilatation produced by 5-HT was resistant to ketanserin but was antagonised by methysergide. 5. Thus 5-HT contracts the tracheal smooth muscle of sheep by stimulating '5-HT1-like' receptors. 5-HT constricts the tracheal vascular bed by stimulating 5-HT2 receptors or dilates the vascular bed by stimulating '5-HT1-like' receptors. 5-HT3 receptors appear not to be involved in the responses of the tracheal vasculature or smooth muscle to 5-HT. PMID- 2331573 TI - Differences in hepatic drug accumulation and enzyme induction after chronic amiodarone feeding of two rat strains: role of the hydroxylator phenotype? AB - 1. It has previously been shown that the extent of hepatic phospholipidosis induced by chronic amiodarone treatment correlates with the degree of drug accumulation in liver tissue. 2. To investigate a possible influence of pharmacogenetic factors, biochemical and morphological investigations were carried out in two rat strains differing in debrisoquine hydroxylation. 3. Plasma and liver tissue concentrations of amiodarone and its main metabolite, desethyl amiodarone, were significantly higher in rats with deficient hydroxylation. Microsomal enzyme induction, drug cytochrome P-450 complex formation and typical ultrastructural features of phospholipidosis were only seen in rats with deficient hydroxylation and in a more sensitive species, the guinea-pig. 4. It remains to be seen whether deficient debrisoquine hydroxylation in man is associated with an increased susceptibility to amiodarone side effects. PMID- 2331574 TI - Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia with reperfusion. AB - In control anaesthetized baboons subjected to 30 min occlusion of the left anterior descending coronary artery, followed by 5.5 h reperfusion, total plasma levels for creatine kinase (CK) and lactate dehydrogenase (LDH) were markedly elevated in a time-related manner. In a second group of baboons pretreated 10 min prior to ischaemia with ranolazine [(+/-)-N-(2,6-dimethyl-phenyl)-4[2-hydroxy-3 (2-methoxyphenoxy)propyl]-1 - piperazine acetamide dihydrochloride; RS-43285-193] at 500 micrograms kg-1 i.v., followed by continuous infusion of 50 micrograms kg 1 min-1, neither enzyme was significantly elevated at any time point. Similarly, serum levels of the cardiospecific isoenzyme CK2 were 8 fold greater in the controls than in the ranolazine-treated animals at 6 h. The results indicate that ranolazine pretreatment abolished cardiac enzyme release over a 5.5 h reperfusion period, indicating a potential protective effect. PMID- 2331575 TI - Pharmacokinetic-pharmacodynamic modelling of the anticonvulsant effect of oxazepam in individual rats. AB - 1. The purpose of this investigation was to examine in vivo drug-concentration anticonvulsant effect relationships of oxazepam in individual rats following administration of a single dose. 2. Whole blood concentration vs time profiles of oxazepam were determined following administration of doses of 4, 8 and 12 mg kg 1. The pharmacokinetics could be described by an open 2-compartment pharmacokinetic model. Following 12 mg kg-1 the values (mean +/- s.e., n = 11) of clearance and volume of distribution were 28 +/- 2 ml min-1 kg-1 and 2.6 +/- 0.31 kg-1, respectively, and were not significantly different from the values obtained at the other doses. 3. The anticonvulsant effect was quantitated by a new technique which allows repetitive determination of the convulsive threshold by direct cortical stimulation within one rat. Significant dose-dependent elevations of the seizure threshold were observed. 4. By pharmacokinetic-pharmacodynamic modelling, a log-linear relationship was found between concentration and anticonvulsant effect. Following 12 mg kg-1 the values (mean +/- s.e., n = 11) of the pharmacodynamic parameters slope and minimal effective concentration (Cmin) were 243 +/- 27 microA and 0.11 +/- 0.02 mg l-1, respectively and not significantly different from the values obtained at the other doses. 5. In a repeatability study the pharmacodynamic parameters were determined twice on two different occasions with an interval of two weeks in the same group of 11 rats. The inter-animal variability in the pharmacodynamic parameter slope was 46%, whereas the intra-animal variability was 24 +/- 18%. The value of the minimal effective concentration was in each animal and on each occasion close to zero within the relatively narrow range of 0.01-0.30mgI. 6. The results of this study showed that it is possible to determine in vivo concentration-anticonvulsant effect relationships of oxazepam under non-steady-state conditions in individual rats. The anti-convulsant effect of oxazepam appeared to be a rapidly reversible direct effect and acute tolerance did not develop within the time frame of the experiments. PMID- 2331576 TI - Reversal of the anorectic effect of (+)-fenfluramine in the rat by the selective cholecystokinin receptor antagonist MK-329. AB - 1. Experiments were conducted to determine whether or not the effect of (+) fenfluramine (3.0 mg kg-1, i.p.) on food intake can be antagonized by the selective cholecystokinin receptor antagonist MK-239 (formerly L364,718; (3S(-)-N (2,3-dihydro-1-methyl-2-oxo-5-phenyl-1-H-1,4-benzodiazepin++ +-3-yl)-1H- indole-2 carboxamide). Two feeding paradigms were employed. In the first, non-deprived rats were familiarized with eating a highly palatable, sweetened mash in a 30 min test. In the second, freely-feeding rats were trained to consume powdered chow in their home-cages, and their intake was monitored over the first 6 h of the night period. 2. In doses of 30.0 and 100.0 micrograms kg-1, s.c., MK-329 almost completely blocked the anorectic effect of (+)-fenfluramine in the palatable food intake test. These doses of MK-329 have previously been reported to antagonize the anorectic effect produced by exogenous cholecystokinin-octapeptide (CCK8) in rats. Both doses of MK-329 were also effective in significantly attenuating the anorectic effect of (+)-fenfluramine in nocturnal free-feeding animals over a 6 h period. 3. MK-329 (10.0-100.0 micrograms kg-1, s.c.) failed to antagonize the anorectic effect of either the specific dopamine D2-receptor agonist quinpirole (0.3 mg kg-1, s.c.) or the beta-carboline FG 7142 (10.0 mg kg-1, i.p.) in the palatable food intake test. 4. MK-329 (10.0-300.Opgkg-1, s.c.) had no effect, when administered alone, on the level of palatable food intake in non-deprived rats, even when substantial satiation was produced by a pre-feeding procedure. Furthermore, MK-329 had no effect, when administered alone, on nocturnal food intake in freelyfeeding rats. 5. In conclusion, not only was MK-329 a potent antagonist of the effect of CCK8 on food intake, it also blocked the effect of (+)-fenfluramine to a significant degree. The effect of MK-329 was selective in that the anorectic effects of either quinpirole or FG 7142 remained unaffected. Administered alone, MK-329 did not affect food intake, indicating that its reversal of (+ -fenfluramine-induced anorexia was not secondary to an intrinsic hyperphagic effect. The results provide some evidence that the depressant effect of (+ )-fenfluramine on food intake depends on the activity of endogenous CCK. PMID- 2331577 TI - Impairment of pulmonary endothelium-dependent relaxation in patients with Eisenmenger's syndrome. AB - A comparison has been made between the endothelium-dependent relaxation of pulmonary arteries (PA) obtained at heart-lung transplantation from 4 patients with Eisenmenger's syndrome and secondary pulmonary hypertension, and PA obtained at lobectomy from 4 patients with lung carcinoma, the controls. All vascular rings were studied immediately after lung excision. PA rings from control patients dose-dependently relaxed to cumulative doses of acetylcholine (ACh, 10( 10) to 10(-5) M), achieving a maximal relaxation of 80 +/- 5% (mean +/- s.e. mean) from precontraction with phenylephrine. By contrast, PA rings from Eisenmenger's syndrome patients achieved a maximal relaxation of only 34 +/- 12% (P less than 0.05, unpaired t test), with even paradoxical contraction at high doses of ACh (10(-6) to 10(-5) M). Sodium nitroprusside (10(-4) M) relaxed all PA rings, with and without endothelium (carefully removed before study), obtained from both control and Eisenmenger's syndrome patients. These results provide the first evidence that endothelium-dependent relaxation of PA mediated by endothelium-derived relaxing factors is impaired in Eisenmenger's syndrome patients with secondary pulmonary hypertension. PMID- 2331578 TI - Stereoselective inhibition of muscarinic receptor subtypes by the enantiomers of hexahydro-difenidol and acetylenic analogues. AB - 1. The affinities of the (R)- and (S)-enantiomers of hexahydro-difenidol (1) and its acetylenic analogues hexbutinol (2), hexbutinol methiodide (3) and p-fluoro hexbutinol (4) (stereochemical purity greater than 99.8%) for muscarinic receptors in rabbit vas deferens (M1), guinea-pig atria (M2) and guinea-pig ileum (M3) were measured by dose-ratio experiments. 2. The (R)-enantiomers consistently showed higher affinities than the (S)-isomers. The stereoselectivity ratios [(R)/(S)] were greatest with the enantiomers of 1 (vas deferens: 550; ileum: 191; atria: 17) and least with those of the p-Fluoro-analogue 4 (vas deferens: 34; ileum: 8.5; atria: 1.7). 3. The enantiomeric potency ratios for compounds 1-4 were highest in rabbit vas deferens, intermediate in guinea-pig ileum and much less in guinea-pig atria. Thus, these ratios may serve as a predictor of muscarinic receptor subtype identity. 4. (S)-p-Fluoro-hexbutinol [(S)-4] showed a novel receptor selectivity profile with preference for M3 receptors: M3 greater than M2 greater than or equal to M1. 5. These results do not conform to Pfeiffer's rule that activity differences between enantiomers are greater with more potent compounds. PMID- 2331579 TI - Alpha-methyldopa induces a naltrexone-insensitive antinociception and hypomotility in rats. AB - 1. This study served to investigate whether endogenous opioid peptides play a role in the putative antinociceptive and the sedative actions of alpha methyldopa. 2. In conscious normotensive rats, alpha-methyldopa induced hypotension, starting around 1 h and reaching a maximum 3-4 h after administration. Pretreatment with naltrexone resulted in an inhibition of alpha methyldopa-induced hypotension. 3. alpha-Methyldopa dose-dependently increased hot plate latency which became evident after a 4 h lag period and reaching a maximum effect at 6 h. The antinociceptive effect of alpha-methyldopa was not affected by naltrexone. 4. In a small open field, alpha-methyldopa dose dependently suppressed locomotion and sniffing behaviour. These effects of alpha methyldopa were apparent 1 h after administration and were naltrexone insensitive. 5. No changes in the level of beta-endorphin-like immunoreactivity in plasma and cerebrospinal fluid were observed after administration of alpha methyldopa. 6. The results indicate that endogenous opioid peptides are involved in the hypotensive action of alpha-methyldopa but not in alpha-methyldopa-induced hypomotility and antinociception. PMID- 2331580 TI - Contractile responses of smooth muscle strips from rat and guinea-pig urinary bladder to transmural stimulation: effects of atropine and alpha,beta-methylene ATP. AB - 1. Strength-duration curves for threshold mechanical responses to single transmural stimuli were identical for rat and guinea-pig detrusor. In both species atropine had no effect on the curves, but the curves were shifted to the right by nerve blockade with tetrodotoxin (TTX), and by blockade of P2 purinoceptors with alpha,beta-methylene ATP (alpha,beta-MeATP). 2. With short duration pulses of 50 V and less, the responses were nerve-mediated. Increase in either the strength or duration of the stimulus caused direct muscle stimulation, resistant to blockade with atropine, TTX and alpha-beta-MeATP. 3. The shape of the contractile response to a single nerve stimulus varied from tissue to tissue. The responses could be mono-, bi-, or multiphasic. Bi- or multiphasic responses were normally seen in tissues which were spontaneously active. The multiphasic nature of the response was enhanced by factors which increased the excitability of the cells and was reduced by factors which decreased the excitability. 4. The frequency-response curves in the rat are similar to those previously obtained in the guinea-pig. Atropine suppresses the high frequency response by 25%, with little effect at low frequencies, whereas desensitization of P2-purinoceptors with alpha,beta-MeATP suppresses the responses maximally at low frequencies but still by 75% at high frequencies. A combination of both drugs eliminates the nerve-mediated responses. 5. It is concluded that the response to a single nerve stimulus is mediated by a non-cholinergic transmitter, through activation of P2 purinoceptors. The possibility that simultaneous release of acetylcholine can modify the excitability of cells and thus the configuration of the response to a single stimulus is discussed. PMID- 2331581 TI - Vascular effects of helodermin, helospectin I and helospectin II: a comparison with vasoactive intestinal peptide (VIP). AB - 1. Helodermin, helospectin I and helospectin II, peptides recently isolated from the salivary gland venom of Heloderma suspectum, were compared to vasoactive intestinal peptide (VIP) with respect to effects on systemic blood pressure and on isolated femoral arteries in the rat. 2. They all reduced blood pressure in a dose-dependent manner; helodermin was less effective than VIP. However, at doses higher than 1 nmol kg-1 all four peptides reduced blood pressure to about the same extent. 3. The half-life of the hypotensive effect of VIP was longer than that of helodermin and the helospectins. 4. VIP and helodermin were equally potent in relaxing femoral arteries precontracted with phenylephrine or prostaglandin F2 alpha. 5. Helospectin I and II relaxed phenylephrine-contracted vessels to the same extent as VIP but with a lower potency. 6. Addition of VIP 1 microM to preparations exposed to helodermin 1 microM or to either of the helospectins did not produce a further relaxation. 7. The findings indicate that VIP, helodermin and helospectin I and II have a similar profile of action and therefore may act on a common receptor. PMID- 2331582 TI - Central inhibition by gamma-aminobutyric acid and muscimol of the release of vasopressin and oxytocin by an osmotic stimulus in the rat. AB - 1. In water-loaded rats under ethanol anaesthesia, the injection of 2-4 microliters 1.54M NaCl solution (hypertonic saline:HS) into a lateral cerebral ventricle (i.c.v.) produced an antidiuretic and a pressor response, together with increased urinary excretion of vasopressin and 'oxytocin-like radioimmunoreactivity' (OLRI). In lactating rats HS also produced a milk-ejection response which was shown to be due to the release of oxytocin. 2. The injection of 20-40 micrograms gamma-aminobutyric acid (GABA) or 40-80 ng muscimol i.c.v. 2 min before HS inhibited the antidiuretic, pressor and milk-ejection responses and reduced the urinary excretion of vasopressin and OLRI. 3. The pressor response to HS was abolished by a ganglion blocking agent but it was not reduced by a vasopressin antagonist. After the antagonist, the antidiuretic response to HS was abolished and the pressor response was accompanied by a diuresis both of which were blocked by muscimol. 4. The threshold dose of HS for an antidiuretic response was 4-8 times higher on injection into the cisterna magna (i.cist.) than when injected i.c.v. GABA, i.v. or i.cist, did not inhibit the response to HS i.c.v. 5. The results confirm other evidence that, in the rat, in contrast some other species, an osmotic stimulus causes release of both vasopressin and oxytocin. This release is blocked by GABA and muscimol. These drugs and HS act at a site reached not from the subarachnoid space but from the cerebral ventricles, probably the hypothalamus. The pressor response to HS under the experimental conditions used is due entirely to central sympathetic stimulation and this effect, as well as the release of vasopressin and oxytocin, is blocked by muscimol. PMID- 2331583 TI - Effects of antiarrhythmic agents classified as class III group on ischaemia induced myocardial damage in canine hearts. AB - 1. The cardioprotective effects of antiarrhythmic agents classified as class III, amiodarone, sotalol and E-4031, were investigated in anaesthetized dogs. 2. The left anterior descending coronary artery was occluded for 2 h. 3. Heart mitochondria were prepared from both the ischaemic and non-ischaemic areas, and their function was estimated polarographically. 4. Activities of the lysosomal enzymes, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were measured in each fraction. 5. Two hour occlusion induced ventricular arrhythmias, and amiodarone, sotalol and E-4031 greatly suppressed the development of arrhythmias. 6. Amiodarone, sotalol and E-4031 significantly protected mitochondria against ischaemia, and prevented ischaemia-induced leakage of lysosomal enzymes. 7. Antiarrhythmic agents classified as class III show cardioprotective effects, which might participate in their antiarrhythmic effect. PMID- 2331584 TI - L-NG-monomethyl arginine and L-NG-nitro arginine inhibit non-adrenergic, non cholinergic relaxation of the mouse anococcygeus muscle. AB - 1. The effects of L-NG-monomethyl arginine (L-NMMA) and L-NG-nitro arginine (L NOARG) on non-adrenergic, non-cholinergic (NANC) relaxations of the mouse anococcygeus were investigated. 2. L-NMMA (10-200 microM) produced a concentration-related inhibition of the NANC response; the inhibitory effect of 50 microM L-NMMA was completely reversed by L-arginine but not D-arginine (both 100 microM). 3. L-NOARG (1-50 microM) also produced a concentration-related inhibition of the NANC response and was some 30-50 times more potent than L-NMMA; again, the effects of 10 microM L-NOARG were reversed by 100 microM L-, but not D , arginine. By itself 100 microM L-arginine did not relax the tissue, but did cause a slight potentiation of the NANC response. 4. Sodium nitroprusside (0.01 10 microM), hydroxylamine (0.1-100 microM), sodium azide (1-100 microM) and nitric oxide (3-120 microM) all relaxed carbachol-induced tone; relaxations to submaximal concentrations of these nitrovasodilators were unaffected by either 50 microM L-NMMA or 10 microM L-NOARG. 5. L-NOARG 10 microM did not inhibit, but rather potentiated, contractions of the mouse anococcygeus due to stimulation of its sympathetic nerves. 6. The inhibitory effects of 10 microM L-NOARG on NANC relaxations were reversed by L-arginine (by 131%), L-citrulline (by 75%), L arginine methyl ester (by 46%) and L-homoarginine (by 22%), but were unaffected by a variety of other amino acids and their derivatives (all at 100 microM). 7. The results provide strong evidence that NANC relaxations of the mouse anococcygeus are mediated by an endogenous nitrate material, probably derived from L-arginine, and confirm that L-NOARG provides a very useful and potent drug for the investigation of endogenous nitrate function. PMID- 2331585 TI - Suramin antagonizes responses to P2-purinoceptor agonists and purinergic nerve stimulation in the guinea-pig urinary bladder and taenia coli. AB - 1. Suramin, an inhibitor of several types of ATPase, was investigated for its ability to antagonize responses mediated via P2X-purinoceptors in the guinea-pig urinary bladder and P2Y-purinoceptors in the guinea-pig taenia coli. 2. In isolated strips of bladder detrusor muscle, suramin (100 microM-1 mM) caused a non-competitive antagonism of responses to alpha, beta-methylene ATP with an estimated pA2 of approximately 4.7, and inhibited responses to stimulation of the intramural purinergic nerves, with a similar pA2 value. At a concentration of 10 microM, suramin had little effect, but at a concentration of 1 microM, suramin potentiated responses to alpha,beta-methylene ATP, and potentiated responses to electrical stimulation of intramural purinergic nerves. 3. In isolated strips of taenia coli, in which a standard tone had been induced by carbachol (100 nM), suramin at 100 microM and 1 mM significantly antagonized relaxant responses to ATP (at an EC50 concentration) with an estimated pA2 of 5.0 +/- 0.82 and relaxant responses to electrical stimulation of the intramural non-adrenergic, non cholinergic inhibitory nerves, either single pulses or trains of 8 Hz for 10 s, with estimated pA2 values of 4.9 +/- 0.93 and 4.6 +/- 1.01, respectively. Suramin had no significant effect at 1 or 10 microM. 4. Suramin, at any of the concentrations tested, did not affect contractile responses to histamine (10 microM) or carbachol (10 microM) in the bladder detrusor preparations. In the taenia coli, suramin did not affect either the relaxant responses to noradrenaline (at an EC50 concentration) or the contractile responses to carbachol (100 nM). 5. Thus, suramin at concentrations above 10 microM blocked actions mediated via P2x- and P2y-purinoceptors in the guinea-pig urinary bladder and taenia coli respectively. Potentiation of purinoceptor-mediated activity was seen only at a low concentration of suramin (1 microM) and only in the urinary bladder (P2x-purinoceptor). For its antagonistic activity suramin did not discriminate between P2X- and P2y-purinoceptors, but it was selective for P2 purinoceptor-mediated activity rather than that mediated via cholinoceptors, adrenoceptors or histamine receptors. PMID- 2331586 TI - Effects of chain-length and unsaturation on affinity and selectivity at muscarinic receptors. AB - 1. Lengthening the chain in diphenylacetylcholine decreases affinity for muscarinic cholinoceptors in guinea-pig ileum. Diphenylacetoxypropyldimethylamine and its quaternary trimethylammonium salt are roughly equiactive: the dimethylamine and the piperidine have some selectivity for ileum compared with atria, but are not as active nor as selective as 4-diphenylacetoxy-N methylpiperidine (4-DAMP) methobromide (MeBr). With the weaker diphenylacetoxybutyl compounds the base is more active than the quaternary salt. 2. The diphenylacetoxybutyl-, cis-butenyl and trans-butenyl compounds have similar affinities. The quaternary salts are less active than the tertiary bases, but they are less selective than the butynyl analogues studied in earlier work. 3. 1,1-Diphenyl-1-hydroxy-2,4-hexadiynyl dimethylamine and its trimethylammonium salt are inactive in concentrations below 100 microM, as are the (+)-camphor sulphonyl ester of 4-hydroxy-N-methyl piperidine and its methiodide. The (+/-) phenylcyclopentylacetyl ester of 4-hydroxy-N-methylpiperidine methobromide is more active than its cyclohexyl analogue and than 4-DAMP MeBr but it is less selective than 4-DAMP MeBr. 4. The high selectivity of p-fluoro-hexahydrosila diphenidol is confirmed but this compound has relatively low affinity (for ileum log K = 7.8). 5. The results indicate steric constraints to binding at muscarinic receptors which could be used to check molecular modelling of the receptor based on its known amino acid sequence. The group binding the charged nitrogen is probably at the mouth of a cavity which can accommodate two large rings (as in 4 DAMP MeBr) but with a depth less than about 7 A so that the rod-like hexadiynes cannot fit. Differences between types of receptor may only involve small changes in geometry secondary to differences in amino acids not directly involved in binding and the production of selectivity depends upon finding substituents which interfere with binding more at one type of receptor than at another. PMID- 2331587 TI - Concentrations of oestradiol-17 beta in plasma and milk and progesterone in plasma during the oestrus cycle and in early pregnancy in goats. AB - Pre-ovulatory peaks in oestradiol-17 beta concentrations were observed on days 1 or 2 and post-ovulatory peaks between days 4 and 7, both in jugular venous plasma and defatted milk, day 1 being the day of the onset of oestrus in the goats. Mean values of the magnitudes of these concentration peaks and of their timing (relative to oestrus) during the oestrus cycle did not differ significantly (P greater than 0.05) from those when the goats were mated and became pregnant. Pre ovulatory oestradiol-17 beta peaks were invariably greater than the corresponding post-ovulatory peaks, as were peak concentrations in plasma relative to those in defatted milk collected on the same day. Mean intervals between the pre- and post ovulatory peaks in oestradiol-17 beta concentrations were respectively 4.2 days for plasma and 4.0 days for defatted milk. Concentrations of oestradiol-17 beta in jugular venous plasma and defatted milk were strongly correlated: rank correlation coefficients for the three goats studied were 0.871, 0.668 and 0.739. It is suggested that in goats, as in cattle, ovarian follicular oestradiol-17 beta secretion approaching pre-ovulatory level is restored by 4 days after oestrus and its rapid decline after this time may be due to the inhibitory influence of the rapidly rising plasma progesterone concentration. PMID- 2331588 TI - The development of a new breed of sheep in Colombia. AB - A new breed of sheep has been developed in Colombia by crossing Scottish Blackface rams with the indigenous Criolla ewes and then interbreeding the progeny, with selection based on performance. It has been given the name Manchada Paramuna. The breed has been developed to provide the small producer (campesino) with a breeding ewe which has a high level of fertility, a good fleece, and which produces lambs with high survival rate and good growth rate. PMID- 2331589 TI - Serum vitamin B12 and methylmalonic acid determinations in the diagnosis of cobalt deficiency in pregnant ewes. AB - Serum vitamin B12 and methylmalonic acid (MMA) concentrations were used to monitor the development of cobalt (Co) deficiency and repletion from the deficient state in housed pregnant hill sheep. Serum MMA concentrations were less variable and provided a more accurate diagnosis of Co deficiency than serum vitamin B12. This was particularly the case for subclinical disease. However, unlike serum MMA, concentrations of the vitamin in serum could be used prognostically. The most precise diagnosis was provided by serum vitamin B12 and MMA data used in conjunction, but where one technique is to be used, serum MMA determinations are preferred. PMID- 2331590 TI - Causes of death and illness in the native sheep of North Ronaldsay, Orkney. I. Adult sheep. AB - Post-mortem examinations on 71 native sheep found dead on the island of North Ronaldsay, Orkney in four visits between April 1983 and July 1985 were carried out. The sheep in this almost feral flock have access to a small area of unmanaged moorland pasture but are otherwise restricted to the foreshore where they subsist largely on Laminaria spp. and other seaweeds. Young adult animals died largely of heavy parasite burdens combined with inadequate nutrition, while the older sheep often starved because of severe dental disease precipitated by heavy deposits of tartar on the cheek teeth--rarely seen in sheep on a more conventional diet. Other underlying metabolic conditions, such as the extensive mineralization of the kidney medulla in many mature sheep, may be debilitating. The pathological findings suggest that adaptation to the peculiar environmental rigours and dietary restrictions on North Ronaldsay is less complete than has previously been assumed. PMID- 2331591 TI - Causes of death in the native sheep of North Ronaldsay, Orkney. II. Lambs. AB - Investigation showed that the common causes of death in North Ronaldsay lambs were trauma due to behavioural patterns and starvation/hypothermia due in part to poor condition of the ewes. PMID- 2331592 TI - The role of Hydrotaea irritans in the transmission of summer mastitis. AB - A series of experiments to investigate the possible role of the sheep head fly, Hydrotaea irritans, in the transmission of summer mastitis is reported. These showed that the pathogens Actinomyces pyogenes and Peptococcus indolicus may be harboured in the gut of the fly for up to 96 h following a contaminated meal; A. pyogenes survived on the surface of the fly for a similar period. H. irritans fed on the pathogens can contaminate a subsequent meal by regurgitation. However, no infections resulted from repeated exposure of the teats of heifers or cows to H. irritans fed on blood containing A. pyogenes and P. indolicus or on pus from a case of summer mastitis. In these experiments the frequency of feeding of the flies on the teat was high but subsequent bacterial contamination of the teat skin was low. Artificial contamination of the teat skin with greater than 10(6) cfu A. pyogenes led to a low incidence of mastitis even in the absence of cutaneous damage. Repeated applications of lower doses (less than 10(4) cfu) did not produce infection. PMID- 2331593 TI - Associations between farmers' personal characteristics, management practices and farm performance. AB - A survey was carried out in a random sample of 123 dairy farms from the east of Ireland. The monthly mean production per cow was 315 l of milk and 11.5 kg of fat. The mean log herd somatic cell count was 5.45 (arithmetic mean = 372,573 cells/ml), with almost 50% of the monthly counts over 300,000 cells/ml in a 12 month period. Bivariate and multivariate analysis was performed to assess the relative impact of the personal characteristics of the farmer and the management policies he applied on the amount and quality of the milk produced. In five out of six models the group of variables related to farmers' attitudes, values, and sociodemographic profile explained a similar or greater amount (between 14.44 and 34.35%) of the variation of farm performance than the group of management variables (between 14.33 and 25.99%) as measured by the R2. These results stress the importance of the human factors in explaining variation in farm performance. PMID- 2331594 TI - Some observations on the effects of age of calves on the phagocytosis and killing of Staphylococcus aureus by polymorphonuclear leucocytes. AB - The effects of age on bovine polymorphonuclear (PMN) cell function were investigated by comparing the efficiencies of phagocytosis and killing of Staphylococcus aureus by peripheral blood leucocytes sequentially obtained from 15 calves between the ages of less than 1 and 84 days. One group of seven calves was kept in a controlled environmental chamber with air temperature of 5 degrees C and 58% relative humidity (RH) and another group of eight calves was kept at 16 degrees C and 58% RH. The calves were given a diet a liquid milk substitute and dry food, and were weaned abruptly from the liquid diet at 35 days of age. The in vitro efficiencies of phagocytosis, and of killing, Staphylococcus aureus by peripheral blood leucocytes were similar for calves in air temperatures of 5 degrees C and 16 degrees C (P greater than 0.05). Peripheral blood leucocytes obtained from calves of less than 1 day of age were more efficient in phagocytosing S. aureus than those obtained when the same calves were 14-84 days of age (P less than 0.001). Peripheral blood leucocytes obtained when the calves were 42 and 56 days of age were significantly less efficient in phagocytosing and killing S. aureus than those obtained when the same calves were less than 1, 14, 28, 70 and 84 days of age (P less than 0.001). PMID- 2331595 TI - Pathological changes in male genitalia of cattle infected with Trypanosoma vivax and Trypanosoma congolense. AB - Samples for histological studies were taken from the genitalia of 14 bulls (five infected with Trypanosoma vivax, five with T. congolense and four uninfected control animals), slaughtered 12, 22 or 30 weeks post-infection. Infection with Y58 strain of T. vivax and strain 2295 of T. congolense caused various grades of lesions in the male reproductive organs, especially the testes and epididymides. T. congolense produced more severe degenerative changes than T. vivax. It is concluded that in long-standing cases, the result of trypanosome infection is either serious infertility or even sterility. PMID- 2331596 TI - Effect of novidium (homidium chloride) chemotherapy on genital lesions induced by Trypanosoma vivax and Trypanosoma congolense infections in Zebu bulls. AB - Zebu bulls chronically infected with Trypanosoma vivax and T. congolense were treated at the 12th week post-infection with novidium and slaughtered at different times after treatment to determine histological evidence of healing of the genital lesions. Though trypanosomes disappeared from the blood soon after chemotherapy, there was incomplete resolution of genital lesions even 10-18 weeks later. Where there is severe degeneration of the testes and epididymes chemotherapy may be ineffective in leading to regeneration and therefore infertility problems may persist in bulls with chronic trypanosomiasis which are later subjected to chemotherapy. PMID- 2331597 TI - Morphological recovery of axotomized goldfish retinal ganglion cells in an environment known to prevent retinotopic refinement of their regenerated tectal arbors. AB - Axonal injury provokes well-characterized morphological changes in goldfish retinal ganglion cells. These reach a peak as the regenerating axons restore a grossly retinotopic projection map to the tectum, and then regress as the map is refined by a mechanism involving locally-correlated activity. The aim of this study was to look for any interdependence between morphological recovery and retinotopic refinement. Stroboscopic light was used to keep regenerated optic arbors in non-retinotopic locations for 70 days after optic nerve cut and lens ablation. Controls were kept in constant or diurnal light, both of which allow refinement of the retinotectal map. Nucleolar frequency, perikaryal area and nuclear area were used as indices of neuronal recovery, and ganglion cell counts were performed. After 35 days in diurnal light, the nucleoli of axotomized cells had increased in size, prominence and number, and both nucleus and cytoplasm had roughly doubled in area. After 70 days, these features had almost returned to normal not only in diurnal and constant light but in stroboscopic light as well. A small but significant cell loss, averaging 13.4-14.7%, was seen after optic nerve cut and lens ablation regardless of stage in regeneration (35 or 70 days) or lighting. Evidently, morphological recovery is independent of retinotopic refinement, which is known to be no further advanced after 70 days in stroboscopic light than after 35 days in diurnal light. PMID- 2331598 TI - Cervical afferent pathway to inferior oblique motoneuron in the cat. AB - The neuronal pathway implicated in the vertical cervico-ocular reflex (COR) was investigated electrophysiologically in chloralose anesthetized cats. The effect of bilateral C2 dorsal root afferent stimulation on inferior oblique motoneurons (IO-MN) was investigated by intracellular recording. Control disynaptic excitatory postsynaptic potentials elicited in IO-MNs following stimulation of the contralateral anterior semicircular canal nerve (ACN) were invariably facilitated by conditioning stimulation to both ipsilateral and contralateral C2 dorsal roots (DR) in all motoneurons tested. This result indicates that inputs from the C2 DR of both sides and the contralateral ACN converge onto secondary vestibular neurons ('common interneurons') which project directly to the IO-MN. Common interneurons mediating vestibular and cervical excitation to the IO-MNs were studied in the vestibular nuclei on the side opposite to the motoneurons by extracellular recording. Nineteen vestibular neurons were identified as common interneurons; they were distributed in the caudal half of the lateral nucleus and the rostral half of the descending nucleus. The present experiment provides electrophysiological evidence of the projection of upper cervical afferents to the ipsilateral vestibular nuclei. The difference in neuronal organization between the horizontal and vertical COR is also briefly discussed. PMID- 2331599 TI - Relationship between uptake of norepinephrine by hypothalamic homogenates and the activity of brown adipose tissue. AB - It has previously been established that norepinephrine (NE) in the central nervous system is involved in feeding and the development of obesity. The present experiments were carried out to investigate the relationship between the uptake of NE by a crude hypothalamic homogenate and NE-mediated sympathetic activity in interscapular brown adipose tissue (IBAT). Sympathetic nervous system activity was assessed by measuring the binding of the purine nucleotide guanosine-5' diphosphate (GDP) to mitochondria isolated from IBAT. Four situations known to alter food intake and sympathetic activity, namely, corticotropin releasing factor infusion, adrenalectomy, fenfluramine treatment and obesity due to genetic transmission were studied. In each case, [3H]NE uptake by the hypothalamic preparation and GDP binding to IBAT mitochondria were measured. A highly significant negative correlation between the uptake of NE by hypothalamic homogenates and the binding of GDP to IBAT mitochondria was obtained in both lean and obese animals. These findings are discussed with regard to the regulation of food intake and sympathetic nervous system mediated thermogenesis. PMID- 2331600 TI - Susceptibility of neurons in area 18a to blockade of area 17 in rats. AB - The present investigation is aimed at studying the influence of the striate cortex (area 17 or V1) upon responses of area 18a. Electrical activity was recorded from neurons in area 18a through glass micropipettes. At the same time lidocaine hydrochloride was injected in the same retinotopic register of area 17. Forty eight cells were tested to diffuse stroboscopic flashes and to localized stationary or moving slits in the receptive field. In addition, orientation selectivity was analyzed in 15 units. Blockade of area 17 produced the following results: discharges to stroboscopic light were unaltered while responses to stationary, localized targets were diminished in about half of the cells. Fifty percent of movement evoked responses were decreased. The orientation properties were particularly sensitive to blockade of area 17. Out of 15 units, 13 had their orientation tuning curves altered by the treatment. These results seem to suggest that the degree of trigger feature complexity depends upon lateral interactions between areas V1 and V2. PMID- 2331601 TI - Amastatin potentiation of drinking induced by blood-borne angiotensin: evidence for mediation by endogenous brain angiotensin. AB - Angiotensinergic synapses in the central nervous system (CNS) have been proposed to be involved in drinking induced by both intracerebroventricular (i.c.v.) and peripheral administration of angiotensins. In the present studies, we tested this hypothesis with i.c.v. application of amastatin, an aminopeptidase A inhibitor, to block peptide degradation. Potentiation of i.c.v. angiotensin II (Ang II) induced drinking responses was observed when amastatin and Ang II were administered. Amastatin did not potentiate drinking to carbachol which demonstrates that the enhancement is specific to peptides. Centrally administered amastatin also potentiated drinking following systemic administration of Asn1 angiotensin II. (Asn1 Ang II). The results are consistent with the hypothesis that CNS angiotensin synapses are involved in the dipsogenic response that results from elevated levels of circulating angiotensin. PMID- 2331602 TI - Changes in levels of microtubule-associated proteins in relation to the outgrowth of neurites from PC12D cells, a forskolin- and nerve growth factor-responsive subline of PC12 pheochromocytoma cells. AB - Immunoblotting analysis and immunofluorescence studies of proteins that react with MAP1- and MAP2-specific antibodies in PC12 rat pheochromocytoma cells were carried out. When cells of the PC12D subline of PC12 cells, which rapidly extend neurites in response to NGF or drugs that elevate intracellular levels of cyclic AMP, were examined, they were found to contain a relatively higher level of MAP1 or of a MAP1-like protein than conventional PC12 cells. Immunoblotting study showed that levels of MAP1 and MAP2 or of MAP1 or MAP2-like proteins increased in PC12D cells, but not in conventional PC12 cells, in response to forskolin. Immunofluorescence studies also revealed increases in levels of MAP1 and MAP2 or of MAP1 or MAP2-like proteins in conjunction with the outgrowth of neurites from the cells. These results support the hypothesis that the induction of MAPs may be one of the first steps required for outgrowth of neurites from PC12 cells. Furthermore, PC12D cells may contain a sufficiently high level of MAP1 or MAP1 like protein to permit the extension of neurites in the absence of the lag period normally required by PC12 cells. The MAP1 or a MAP1-like protein was localized in the cell soma and neurites. An increase of MAP2-specific immunoreactivity in perikarya was observed in the differentiated cells. After immunostaining with a monoclonal antibody that reacted with phosphorylated MAP1, intense fluorescence was seen in the growth cones of neurites. This observation supports the hypothesis that the phosphorylation of MAP1 or of a MAP1-like protein may play a regulatory role in the formation of neurites in growth cones. PMID- 2331603 TI - Water response of frog olfactory system is induced by a decrease in osmotic pressure. AB - The frog olfactory response to deionized water (water response) was recorded from the olfactory bulb. The water response was suppressed by both electrolytes and non-electrolytes as a function of osmolarity, while the water response in taste cells was not suppressed by non-electrolytes. It was concluded that a decrease in osmotic pressure induced by application of deionized water is the origin of the water response in the frog olfactory system. PMID- 2331604 TI - Induction of class II major histocompatibility complex antigens on a population of astrocytes from a mouse strain (BALB/c) resistant to experimental allergic encephalomyelitis. AB - We have investigated the capacity of the lymphokine gamma-interferon (IFN-gamma) to induce class II major histocompatibility complex (MHC) antigens on astrocytes cultured from BALB/c mice. This is a mouse strain resistant to experimental allergic encephalomyelitis (EAE), and in a recent report Massa et al. (Proc. Natl. Acad. Sci. U.S.A., 84 (1987) 4219-4223) indicated that BALB/c astrocytes in vitro were not susceptible to class II MHC antigen induction by IFN-gamma. We observed, in agreement with this previous report, that when primary cultures of astrocytes from neonatal BALB/c mice were just at confluence (7-10 days in vitro), IFN-gamma did not stimulate expression of class II MHC antigens. However, after 14-16 days in vitro, a population of astrocytes emerged in the cultures on which class II MHC antigens could be induced. These cells expressed the astrocyte marker glial fibrillary acidic protein, and were found in close association to small round superficial cells (multipotential precursor cells), and to microglia. These results indicate that the ability of astrocytes to respond to lymphokine stimulation is not completely correlated with susceptibility to EAE, and further suggest the importance of central mechanisms in the development of inflammatory brain disease. PMID- 2331605 TI - Protective effect of alpha-tocopherol on ischemic neuronal damage in the gerbil hippocampus. AB - The effect of alpha-tocopherol (vitamin E) on ischemic neuronal damage was studied in the gerbil. The animals were subjected to 5 min of cerebral ischemia by bilateral common carotid artery occlusion. Immediately after ischemia, alpha tocopherol at a dose of 50 or 100 mg/kg was administered intravenously. Morphological changes in the CA1 sector of the hippocampus were evaluated after 7 days of survival. alpha-Tocopherol prevented ischemia-induced neuronal death. The average density of CA1 pyramidal neurons (cells/mm, mean +/- S.E.M.) was 252 +/- 8 (n = 8) in the sham-operated group, 50 +/- 20 (n = 8) in the ischemia group, and 140 +/- 35 (n = 8) and 182 +/- 36 (n = 8) in the groups treated with alpha tocopherol at the doses of 50 and 100 mg/kg, respectively. The results suggest that free radical scavenging action of alpha-tocopherol played an important role in preventing the neuronal death. PMID- 2331606 TI - Modeling the repetitive firing of retinal ganglion cells. AB - A kinetic model for the repetitive firing of retinal ganglion cells was synthesized from voltage-clamp data and evaluated by comparison with whole cell recordings from ganglion cells in the intact tiger salamander retina. Five distinct channels were included in the model and were sufficient to describe the physiologically observed frequency/current relationship in response to various levels of cell depolarization. PMID- 2331607 TI - Embryonic motoneurons grafted into the adult CNS can differentiate and migrate. AB - Embryonic mouse motoneurons were labelled by retrograde transport with a fluorescent dye (diI), partially purified on a density gradient and grafted into adult mouse CNS for a maximum of 10 weeks. In both the spinal cord and striatum, a small number of fluorescently labelled motoneurons were found to survive as judged by their round, bright appearance and also to differentiate as assessed by their ability to extend neurites. The motoneurons travelled long distances in the spinal cord (2 mm) and in the brain (4 mm) in both white and grey matter. PMID- 2331608 TI - The distribution of changes in local cerebral energy metabolism associated with brain stimulation reward to the medial forebrain bundle of the rat. AB - Using the quantitative 2-[14C]deoxyglucose autoradiographic method, local rates of glucose utilization were measured in rats during brain stimulation reward to the medial forebrain bundle. Metabolic activation was observed both rostral and caudal to the site of stimulation. These sites included the nucleus accumbens, olfactory tubercle, lateral septum, and ventral tegmental area. In many cases, increases in glucose utilization occurred bilaterally. These data suggest the involvement of both ascending and descending systems in brain stimulation reward. Furthermore, despite the unilateral nature of the electrical stimulation, increases in glucose utilization were observed both ipsilateral and contralateral to the site of stimulation. PMID- 2331609 TI - Cholinergic synaptic vesicles are metabolically and biophysically heterogeneous even in resting terminals. AB - The metabolic heterogeneity of synaptic vesicles in the cholinergic nerve terminals of the electromotor neurons of Torpedo marmorata has been studied in resting tissue by evaluating the molecular acetylcholine content (MAC) of synaptic vesicles after extraction from frozen and crushed tissue and high resolution centrifugal density gradient separation in a zonal rotor. Although vesicular acetylcholine was distributed in the gradient as a single, more or less symmetrical peak, 3 subpopulations of synaptic vesicles could be identified: a small, relatively light subpopulation of low MAC on the ascending limb of the acetylcholine peak, designated V0, a main population of fully charged vesicles designated V1, and a small, denser subpopulation also of low MAC on the descending limb of the acetylcholine peak, designated V2. The mean proportions and MACs of the 3 pools were: V0, 13%, 58,000; V1, 53%, 246,000; V2, 34%, 79,000. When tritiated acetate was perfused through excised blocks of electric organ for 1-2 h before vesicle isolation, the specific radioactivity of the acetylcholine in the V0 and V2 pools was 10-30 times higher than in the V1 pool. This suggests that both the V0 and V2 pools are not generated by the isolation procedure but are present in the intact endings and are functionally active. On the basis of their density and uptake of newly synthesized acetylcholine, the V0 and V2 pools were identified with the previously described VP0 pool of axonal vesicles and the VP2 pool of recycling vesicles in stimulated nerve terminals respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331610 TI - Do CNS anlagen have plasticity in differentiation? Analysis in quail-chick chimera. AB - Heterotopic transplantations of brain vesicles of a quail embryo into a chick embryo were carried out in order to elucidate if CNS anlagen have plasticity in differentiation at the 7-10 somite stage. Quail cells are distinguished from chick cells due to the difference in nuclear morphology. The prosencephalon did not differentiate into the cerebellum when transplanted into the metencephalon, although previous study showed that the prosencephalon has the capacity to differentiate into the optic tectum. The mesencephalon differentiated as an optic tectum when transplanted into the prosencephalon or into the rhombencephalon. The metencephalon differentiated as a cerebellum in the telencephalon. It is concluded that only the prosencephalon has limited plasticity, but the mesencephalon and rhombencephalon are determined by the 7-10 somite stage. PMID- 2331611 TI - The effect of M1 muscarinic blockade on behavior and physiological responses following traumatic brain injury in the rat. AB - Dicyclomine (1 mg/kg or 10 mg/kg), scopolamine (1 mg/kg), or saline was administered intraperitoneally to rats 15 min prior to moderate fluid percussion brain injury. A variety of reflexes and responses were measured up to 60 min following injury, and body weight and several neurological measures were taken daily up to 10 days following injury. All 3 antimuscarinic treatments reduced the duration of transient behavioral suppression as assessed by these measures. It appears that blockade of the M1 muscarinic receptor can attenuate transient behavioral suppression associated with concussive brain injury. Thus, stimulation of M1 muscarinic receptors may mediate components of reversible traumatic unconsciousness following cerebral concussion. No differences were observed between saline and antimuscarinic treatments in the incidence or duration of apnea following injury. Scopolamine pretreatment significantly elevated heart rate prior to injury, but had no significant effect on the responses of heart rate and blood pressure to experimental concussion. Both doses of dicyclomine significantly reduced resting heart rate, but unlike scopolamine, significantly enhanced the cardiovascular response to fluid percussion injury. Antimuscarinic treatment significantly reduced body weight loss and certain motor deficits, including beam balance and beam walk performance, following concussive head injury. Scopolamine and both doses of dicyclomine appeared to be equally effective in reducing long-term deficits. Data from these experiments indicate that at least some of the long-term behavioral deficits following moderate levels of brain injury may involve the binding of acetylcholine to M1 muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331612 TI - Peptidergic transmission in the brain. II. Mediation by a vasopressin-like peptide. AB - The medial amygdaloid nucleus (AME) sends a projection of fibers containing a peptide similar to arginine vasopressin (AVP) to the rat hippocampus. Electrical stimulation of the AME has an impact on evoked hippocampal field potentials that is identical to the effect obtained by applied AVP in vitro or in vivo. Here we show that the AVP-like peptide released by AME stimulation has action that is blocked by a structural AVP analog. The antagonist specificity suggests that the native transmitter is a peptide similar, but not identical, to AVP. We conclude that the AME projection to the hippocampus satisfies all the criteria for recognition as a central peptidergic system important in the generation of behavior. PMID- 2331613 TI - Circadian rhythms in spontaneous neuronal discharges of the cultured suprachiasmatic nucleus. AB - The suprachiasmatic nucleus (SCN) is believed to play a major role in the generation and control of circadian rhythms in mammals. In order to obtain further evidence concerning this, single and multiple neuronal discharges were continuously recorded over a period of several days in neonatal rat SCN explants. These organotypic explants, which had been cultured for several weeks in a chemically defined medium, showed alternating high and low levels of spontaneous neuronal discharges with a periodicity around 24 h. Such explants can serve as a useful model to study the neuronal mechanisms underlying the generation of mammalian circadian rhythms. PMID- 2331614 TI - Anatomic evidence for a neurotoxic effect of (+/-)-fenfluramine upon serotonergic projections in the rat. AB - Immunocytochemistry was used to determine whether (+/-)-fenfluramine causes structural damage to serotonergic (5-HT) neurons. Sections from rat forebrain were examined 4 h, 36 h and 2 weeks after various dose regimens of fenfluramine. At all time points there was a reduction of fine 5-HT axon terminals in the forebrain, while beaded axons were spared. The presence of markedly swollen, fragmented 5-HT axons 36 h after injection is indicative of axonal degeneration, and provides morphologic evidence for a neurotoxic effect of (+/-)-fenfluramine upon 5-HT axon terminals. PMID- 2331615 TI - Pulpal and cutaneous inputs to somatosensory neurons in the parabrachial area of the cat. AB - The majority of somatosensory neurons recorded from the mesencephalic parabrachial area and pontine parabrachial nucleus of the cat responded exclusively to noxious mechanical stimuli to the skin. Their receptive fields were very large. Two-thirds of the neurons tested responded to electrical stimulation of the tooth pulp. These results suggest that neurons in this area have extensive convergence of spinal and trigeminal inputs, and contribute to the affective or autonomic aspects of pain. PMID- 2331616 TI - Posthoc phosphorylation of proteins derived from ischemic rat hippocampus, striatum and neocortex. AB - Disruption of the brain's protein phosphorylation system by ischemia may cause irreversible metabolic and structural alterations leading eventually to cell death. To examine the effect of ischemia on the phosphorylation state of brain proteins, tissue homogenates derived from the hippocampus, striatum and neocortex of normal rats and rats subjected to severe forebrain ischemia were phosphorylated with [gamma-32P]ATP. The phosphorylated proteins were separated by two-dimensional polyacrylamide gel electrophoresis and changes were assessed by autoradiography. Cerebral ischemia caused marked alterations of the phosphorylation state of many brain proteins; phosphorylation of some proteins was increased while phosphorylation of others was decreased. Despite differences in the sensitivity of the hippocampus, striatum and neocortex to ischemic injury the direction and approximate magnitude of protein phosphorylation changes caused by ischemia were similar in all three regions. Since the pattern of protein phosphorylation in the ischemia-vulnerable hippocampus was identical to that in the ischemia-resistant paramedian neocortex we conclude that abnormalities of protein phosphorylation may be necessary for ischemic injury to neurons but none are sufficient to explain the selective vulnerability of certain brain regions to ischemic damage. PMID- 2331617 TI - Kindling increases the K(+)-evoked Ca2(+)-dependent release of endogenous GABA in area CA1 of rat hippocampus. AB - The release of endogenous amino acids from hippocampal CA1 subslices under basal conditions and the release evoked by high potassium (50 mM K+) depolarization was studied during kindling epileptogenesis. Emphasis was put on the release of the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate. Kindling was induced by tetanic stimulation of the Schaffer collaterals/commissural fibers of the dorsal hippocampus of the rat. The calcium dependent GABA release in the presence of high K+ was significantly increased (40 46%) in fully kindled animals, 24 h after the last seizure, in comparison to controls. At long-term, 28 days after the last seizure, the calcium-dependent GABA release was still significantly increased (45-49%). An increased release of GABA in kindled animals was still found when GABA uptake was blocked by nipecotic acid. In contrast, no significant alterations were encountered in the basal or high potassium induced release of the excitatory amino acids aspartate and glutamate. These results suggest that kindling epileptogenesis is accompanied by a specific and long-lasting enhancement of GABA exocytosis which may lead to a desensitization of the GABA receptor, and thus determine the increase of seizure sensitivity. PMID- 2331618 TI - Peptidergic transmission in the brain. I. Vasopressin-like signal in the hippocampus. AB - Studies of the action of arginine vasopressin (AVP) in the rat hippocampal slice have produced a model of the peptide's neural action. AVP excites local circuit inhibitory interneurons and causes consequent inhibition of pyramidal cells that is apparent as a reduction in the amplitude of the evoked population spike in field potential recording. Here we show that applied AVP does the same thing to the evoked population spike in the whole animal. Then we show that stimulation of the source of hippocampampal AVP, the medial amygdaloid nucleus, also inhibits the evoked population spike. Analysis of the synaptic potential indicates that the same mechanisms are employed by exogenously applied and endogenously released peptide. The inhibition can only be obtained by stimulating those brain structures known to project vasopressin fibers to the hippocampus. The stimulus response characteristics and kinetics of the endogenous signal correspond to the properties of peptidergic signals in simple systems. The results are taken to support a transmitter role for AVP in the rat hippocampus. PMID- 2331619 TI - 5-HT2 and 5-HT3 receptors mediate two distinct depolarizing responses in rat dorsal root ganglion neurons. AB - The effects of serotonin (5-HT) were studied on transmembrane potentials in 188 rat dorsal root ganglion cells (150 A-type, 16 C-type and 22 unidentified neurons). 5-HT produced a concentration-dependent depolarization in 88% of these neurons. Membrane input resistance (Rin), determined from the slope of current voltage displacement curves, was increased in 51% and decreased in 41% of the responding neurons. Both responses occurred in 8% of the neurons. No differences in these responses were observed between A- and C-type neurons. Norepinephrine (NE) depolarized 75% (n = 20) of the neurons tested while increasing the Rin. In cells where 5-HT decreased Rin, 2-methyl 5-HT, but not alpha-methyl 5-HT, mimicked the response. The selective 5-HT3 antagonist, ICS 205-930, blocked this response, but ketanserin and methiothepin did not affect it. The 5-HT-induced increase in Rin was blocked by 5-HT2 antagonists (ketanserin, methiothepin and spiperone); mimicked by alpha-methyl 5-HT, but not affected by 2-methyl 5-HT. The selective 5-HT3 antagonist, ICS 205-930, did not antagonize this response. The action of NE but not 5-HT was blocked by the selective alpha 1 antagonist, prazosin. These data indicate that the 5-HT induced depolarization with decreased Rin is mediated by 5-HT3 receptors and the depolarization with increased Rin is mediated by 5-HT2 receptors. Furthermore, these two receptors can occur on the same cell. PMID- 2331620 TI - Evaluation of blood vessel and neurite growth into a collagen matrix placed within a surgically created gap in rat spinal cord. AB - A complete gap of 3-4 mm was surgically created in the spinal cord of adult rats between the T8-T10 vertebral level, filled with a collagen matrix and closed with sutures. Animals were killed at weekly intervals from 14 to 42 days postimplantation. The collagen implant (CI) was evaluated for ingrowth of blood vessels and neurites using light and electron microscopic techniques. At 42 days postimplantation, 3 CI animals underwent a transection at the rostro-caudal center of the CI followed by placement of horseradish peroxidase (HRP) impregnated filter paper between the cut ends. The number and location of HRP labeled cells in CI animals were compared to normal animals that received a spinal cord transection at the T9 vertebral level immediately followed by placement of HRP between the cut stumps of spinal cord. Connective tissue (CT) septae, neurites and blood vessels invaded the CI from adjacent spinal neuropil and surrounding CT capsule. CI animals revealed HRP-labeled cells in the intermediolateral cell column (IML), parabrachial nuclei, locus coeruleus and red nucleus with a preponderance of labeled cells found in the IML rostral to the CI. In contrast, no IML were labeled in thoracic spinal cord rostral to HRP implantation in control animals. It was concluded that the above brainstem nuclei, which normally project axons into spinal cord, are capable of extending their severed axons into the CI following spinal cord injury and that uninjured IML cells also sprout axons into the CI. PMID- 2331621 TI - Synthesis, release and receptor binding of acetylcholine in the C1 area of the rostral ventrolateral medulla: contributions in regulating arterial pressure. AB - This study sought to determine whether release of acetylcholine (ACh) within the C1 area of nucleus reticularis rostroventrolateralis (RVL) contributes to the tonic maintenance of arterial pressure (AP) in the rat. The activity of choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh, varied 5.5-fold in micropunches of the 6 medullary regions examined. ChAT activity in the C1 area (179 +/- 35 nmol [14C]ACh formed/mg protein/60 min; n = 4) was intermediate between that of the hypoglossal nucleus (249 +/- 38; highest) and the pyramids (45 +/- 11; lowest) and equivalent to that found in the parietal cortex (147 +/- 15). Release of [3H]ACh from C1 area micropunches was increased by raising extracellular K+ concentrations (5-55 mM) and was entirely Ca2(+)-dependent. Muscarinic receptor binding density was assessed using [3H]quinuclidinyl benzylate ([3H]QNB) as ligand and a recently developed 'electronic micropunch' technique which allows measurement of quench-corrected [3H]QNB binding within corresponding cylinders of tissue obtained by the mechanical micropunch cannula. [3H]QNB binding density varied 2.6-fold: lateral reticular nucleus pars lateralis greater than C1 area greater than nucleus ambiguus = hypoglossal nucleus = pyramid = oral spinal trigeminal nucleus. In urethane-anesthetized rats, inhibition of ACh synthesis by hemicholinium-3 (HC-3, 3 nmol/50 nl), or blockade of muscarinic receptors by scopolamine (SCOP, 3 nmol/50 nl), reduced resting mean AP by 18-24 mm Hg following bilateral microinjection into the C1 area. These concentrations of HC-3 and SCOP were sufficient to attenuate by 70-80% the increase in local cholinergic neurotransmission elicited by the cholinesterase inhibitor physostigmine given systemically. High concentrations of SCOP (30-150 nmol/50 nl) lowered AP by 46-60 mm Hg. Similarly, bilateral microinjections of GABA (10 nmol/50 nl) into the C1 area markedly reduced mean AP by 51 +/- 6 mm Hg to levels normally found after transection of the spinal cord. Thus, a substantial portion of tonic sympathetic activity may be driven by activation of muscarinic receptors in the C1 area. In the spontaneously hypertensive rat (SHR), a genetic model of hypertension, neither spontaneous nor K(+)-evoked release of [3H]ACh from the C1 area differed from that of normotensive Wistar-Kyoto rats (WKY).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2331622 TI - AIDS and CDIP. PMID- 2331623 TI - Writer 'misrepresents my data'. PMID- 2331624 TI - 'Basic information' or 'hucksterism'? PMID- 2331625 TI - Re: 'Comments by Dr. McComb'. PMID- 2331626 TI - 'Surprised' by several comments. PMID- 2331627 TI - Putting hubby through--the compensatory support conundrum. PMID- 2331628 TI - The behaviour of the geriatric patient. AB - The geriatric patient is subject to singular stresses associated with old age. They include physical illness which is often multiple and chronic in nature; degenerative age changes which are part of the normal physiologic aging process and psychological and sociological disturbances. These factors and others mediated by the personality of the patient give rise to behavioral problems that influence the dentist's treatment plan and his ability to perform clinical procedures. An examination is made of this element in the dental situation and recommendations are outlined for its management. PMID- 2331629 TI - Self-reported medical conditions and drug use among elderly dental patients. AB - There is a paucity of data describing the prevalence of systemic conditions and drug use in elderly dental patients. In this study, the charts of all patients, 65 years of age and older who were accepted for dental treatment at the University Dental Clinic in Saskatoon, Canada, during the period from January 1986 to April 1988 were reviewed. Data was obtained from a self-administered questionnaire and an oral history sheet. Cardiovascular diseases (27 per cent), orthopedic problems (24 per cent), and endocrine disorders (16 per cent), were the most commonly reported systemic conditions. Approximately 15 per cent of these patients were taking three or more medications at the time of examination. Dentists should be aware of alternate approaches for treating the medically compromised elderly patient. These findings emphasize the importance of obtaining an adequate drug history prior to commencing dental treatment. Guidelines are required to enable dental clinicians to make informed decisions, in order to provide the most appropriate therapy for this growing segment of our population. PMID- 2331630 TI - [The dental health of institutionalized elderly patients: from awareness to action]. AB - Too often survey reports, studies and well advised considerations by health researchers follow one another and pile up without any real application in the day-to-day life. For example, most health professionals and health care workers and even the public in general have deplored the fact, when they read the study done by Brodeur and Simard in 1982 on the dental health of the elderly, that 72 per cent of the Quebecers of 65 years of age and older were edentulous. Yet, since this study has been published, there has been no blitz or systematic action to improve the dental health of the elderly. Unless I'm mistaken, efforts were made mostly to promote prevention among the younger generations. In the Quebec Province, the works of Dr Vallee have of course fostered some progress in the field of Geriatric Dentistry. However, it must be said again that real positive actions for the elderly patients remain few if not exceptional. Perhaps are we right when we say that seniors as a social group are somewhat neglected. Perhaps also do we consider them as a group for which there is not much left to be done... In reality, dental healthwise, is there anything better than to wish for the young generations not to have the deplorable fate of the elderly? PMID- 2331631 TI - Embedded blank trials: their influence on error recognition ability. AB - On some occasions, mixing knowledge of results (KR) and Blank trials (No-KR) during acquisition has increased retention relative to when Blanks were absent. The proposal that Blank trials improve retention because they encourage the development of the internalized error recognition system was not supported. PMID- 2331632 TI - Facial and verbal congruency: effects on perceived verbal and emotional coaching feedback. AB - The present study investigated the effects of facial-verbal expression congruencies on the perception of a coach's verbal and emotional feedback. The design was a two (facial congruency) by two (verbal feedback) completely randomized factorial. The facial expression was either congruent or incongruent with verbal feedback. Seventy-one university students (39 males, 32 females) were randomly assigned to one of the four experimental conditions. Each student watched a videotape of facial-verbal pairings and evaluated (a) the percentage of positive and negative statements, (b) the emotions expressed by the coach. The analysis indicated that incongruent facial expressions distorted, in a negative direction, the expected frequency of positive feedback. The emotional state findings illustrated that the presence of any negative stimuli (face or verbal) produced the perception of negative affect. The findings provided converging evidence that inconsistencies in facial-verbal expression have a powerful effect on the perception of verbal feedback and emotional state. PMID- 2331633 TI - Heart rate and blood lactate concentration during on-ice training in speed skating. AB - Heart rates and blood lactate concentrations were measured in four sprint and three all-round male members of the Canadian National Speed Skating Team. Responses to various training programs were obtained over a two-week period in November following four weeks of ice training, and in January during mid-season competition. Seven different training programs used by sprint and all-round speed skaters were monitored including a skating velocity and heart rate/lactate response. The protocol for this response was 5 x 4 min exercise intervals with 4 min recovery. A significant increase in blood lactate (3.9 +/- 0.4 to 5.2 +/- 0.5 mmol.L-1) was observed between intensity levels 2 and 3. During the specific 1500 m training program for sprinters, there was an increase in blood lactate and a decrease in heart rate for each exercise interval, despite a maintenance in lap speed throughout the whole program. The highest blood lactate concentrations seen in training and competition were 18.5 +/- 0.3 mmol.L-1 in specific 1500 m training and 17.7 +/- 1.8 mmol.L-1 following the 1000 m race. PMID- 2331634 TI - [Analysis of non-optimal behavior in a dichotomous choice situation]. AB - Proteau and Girouard (1987) have recently proposed a model to explain the decisional process that takes place in a two-choice reaction time situation. Although the model was well supported by the experimental data reported by these authors, a few unexplained results were observed and hypotheses were suggested to account for them. The goal of the present experiment was, first, to replicate the results presented by Proteau and Girouard (1987) to support their model. Our second goal was to determine if the unexpected results reported by these authors can be linked to some particular conditions occurring in the normal course of an experiment. The results obtained in the present experiment totally supported the proposed model. Furthermore, a detailed analysis of the circumstances under which unexpected results occurred did not permit the identification of any particular conditions favoring their occurrence. In conclusion, the proposed model, although reliable for about 95% of the trials, is still imperfect. PMID- 2331635 TI - Verbal and non-verbal feedback from coaches. PMID- 2331636 TI - Use of augmented feedback for the modification of the pedaling mechanics of cyclists. AB - On-line computer representation of forces applied to the pedals during a 90 degree sector of the pedaling cycle were used to train a group of cyclists to alter their pattern of force application while they cycled on a stationary cycle. The subjects rode for 32 min each day for ten days. During these training rides, three cyclists were given augmented feedback on only their pedaling rate, while three other cyclists were presented with augmented, visual feedback on the magnitude of force application in the sector of interest as well as cadence. At the end of the training period it was noted that the experimental group showed significantly reduced pedal forces in the sector of interest while the control group did not. It was concluded that this technique of modifying a well-practised task was an effective one and that it could be used to explore various training modalities and other pedaling styles. PMID- 2331637 TI - Lactate levels in skaters. PMID- 2331638 TI - Defining information feedback. PMID- 2331639 TI - [Metabolic fatigue and the performance of visual tasks]. AB - The aim of this study was to analyse the effects of different types of metabolic fatigue, induced by anaerobic alactacid, anaerobic lactacid, sub-maximal aerobic, and maximal aerobic efforts, on the performance of a sensory task (peripheral threshold detection), a sensory-motor task (coincidence-anticipation), and a cognitive task (recall in central vision). Each of three experimental groups performed one of the above-mentioned tasks under all types of fatigue. Running bouts on a treadmill were used to induce the different types of fatigue. Results show that performance in peripheral vision improves with all types of effort. For coincidence-anticipation, only constant error is affected by anaerobic alactacid and maximal aerobic efforts; the former producing a change in behavior from lateness to anticipation, whereas the latter significantly reduces lateness. Finally, performance in the cognitive task is significantly disturbed by the maximal aerobic exercise. It is suggested that, while sensory and adaptive behaviors improve with previous physical work, cognitive behavior is handicapped by highly demanding activities, that is, activities requiring aerobic maximal efforts. PMID- 2331640 TI - An experiential perspective on the motivational features of exercise and lifestyle. AB - The purpose of this study was to describe the cognitive, emotional and behavioral concomitants of direction, intensity and persistence for exercise in individuals displaying different levels of exercise involvement. In order to attain this goal, 78 one-hour interviews were conducted with individuals who were either autonomous exercisers, fitness program enrollees, fitness program dropouts or sedentary individuals. Subjects were asked to describe their thoughts, feelings and behaviours, before, during and after a workout, and trained interviewers used probes to further tease out aspects of direction, intensity and persistence. Findings were content-analyzed to detect significant trends. Results revealed that autonomous exercisers differed from individuals with less active lifestyles in several ways: participation motives were geared mainly toward fitness-health; the aspect they enjoyed the most about their participation was the task itself; they did not need to do any planning to ensure that they regularly attended their workouts; they expended a moderately high amount of effort and intensity in pursuing their exercise; they conceded that sometimes they missed workouts simply out of fatigue and that they felt that something was missing in their life when they did not exercise. By contrast, other types of exercisers displayed different profiles. These findings replicate and extend data available in the literature and thus support the viability of qualitatively conceptualizing and assessing motivation in exercise settings. PMID- 2331641 TI - Evaluation of an indoor standardized obstacle course for Canadian infantry personnel. AB - This study compared performance on an indoor standardized obstacle course (ISOC) to laboratory measures of fitness recognized as important in the performance of infantry tasks. The course involves 19 obstacles consisting of running, crawling, scaling, pulling, lifting, carrying and pushing activities arranged in sequential order. Forty-three healthy males between 21 and 31 years of age participated in the study. Performance scores on the ISOC were found to be significantly (p less than 0.01) and positively correlated to maximal aerobic power (MAP), muscular strength and endurance and anaerobic lactic power, and negatively correlated to indices of body fat. Stepwise multiple regression analysis indicated that 81% of the variance in ISOC performance time was accounted for by MAP, a strength index, anaerobic lactic power and sum of four skinfolds. PMID- 2331642 TI - Central fatigue and lactate levels. PMID- 2331643 TI - Relationship between the starting age of training and physical fitness in old age. AB - The purpose of this study was to test the hypothesis that older persons can minimize the reduction in physical fitness with aging if they start training before approximately 50 years of age, beyond which strength decline has been reported to become more pronounced. Maximal values for isometric strength, dynamic strength and speed of movement of the biceps brachii and quadriceps muscles, back-lift strength, and predicted oxygen uptake (VO2max = VO2max) were measured in 39 male subjects who were 60-68 years old. Four groups were studied: T26, T45, T56, and untrained. The T26 group had been training (jogging 10 km.day 1, 5 days.wk-1 at 10 km.h-1) since before their mid-thirties (mean 26 years), the T45 group since their forties (mean 45 years), the T56 group since their fifties (mean 56 years), and the untrained group had never taken part in any systematic training. Collectively, the T26 and T45 groups had significantly (p less than 0.05) higher values for muscle strength, speed of contraction, and VO2max than the T56 and/or untrained group(s). However, no differences were observed between the T26 and T45 groups. The results support a relation between the starting age of training and the age-dependent decline of physical fitness. Thus, the hypothesis is accepted. PMID- 2331644 TI - Motivation and exercise adherence. PMID- 2331645 TI - An inexpensive electronic counting system for step tests. AB - A simple electronic counter was designed to count step test cadence. Foot pads, a controller and a counter were used to record the number of times the subject placed both feet on the top step. The electronics insured accurate counting by preventing double counts on one ascent and requiring weight to be put on both feet on the top step. PMID- 2331646 TI - Risk of automobile accidents in cigarette smokers. AB - I used a case-control study to identify an increased risk of motor vehicle crash (MVC) in cigarette smokers as compared to non-smokers. Information on smoking status and potential confounding factors was obtained using a self-administered mail-out questionnaire sent to 1,000 persons known to have had a MVC, and a control group of 1,100 persons with no record of MVC in the previous five years. Assessment of relative risk estimates (RR) and adjustment for confounding factors was done by logistic regression analysis. Smokers had a 1.5-fold increase in risk for MVC over non-smokers (p = .01). Also, an increased tendency to smoke while driving was associated with greater risk of MVC (X2 trend: p = .01). The basis for this association may be: 1. distraction from driving by the act of smoking. 2. behavioural differences between smokers and non-smokers. 3. carbon-monoxide toxicity. Further study is needed to determine the importance of these factors as components of the increase in risk found. PMID- 2331647 TI - A study of mortality near sour gas refineries in southwest Alberta: an epidemic unrevealed. AB - Concerns about excesses in a wide array of adverse health outcomes have been expressed for over 25 years by a rural population in southwestern Alberta, living downwind from natural gas refineries. Among these has been the perception that deaths have occurred more frequently than ought to have been expected. As part of a large field epidemiologic study undertaken during the summer of 1985 to investigate possible health effects in this area, a residential cohort study was carried out to study mortality. The cohort was defined as all those individuals who resided in the area in 1970. A total of 30,175 person-years of risk within Alberta were experienced by this cohort during 1970-84. The deaths during this period were enumerated by resident reports and by manual record linkage with the death records of the Alberta Bureau of Vital Statistics. Age- and sex standardized mortality ratios, based on expected rates from 2 pre-specified demographically similar, non-metropolitan Southern Alberta populations, were 0.88 and 0.84 respectively, neither of which was significantly different from unity. These data cannot address the question of etiology but they can do much to allay the anxieties of a community convinced it had experienced an epidemic of death. PMID- 2331648 TI - The oral health status and treatment needs of adults aged 65+ living independently in Ottawa-Carleton. AB - We report the findings from a dental survey of a random sample of 299 senior citizens living in Ottawa-Carleton. Those examined were younger, less likely to have a regular dentist, and more likely to have oro-facial pain, difficulty chewing, and to perceive a need to visit a dentist compared with those responding to the enrollment phone interview. Among the 65% of seniors who were dentate, 37% had dental decay; men and seniors with low incomes had more decay (p less than 0.05). Periodontal disease was worse among older seniors, men and poor seniors (p less than 0.05). One third of all seniors reported recent oro-facial pain, 50% had difficulty chewing foods and 30% reported some social impact resulting from their oral health. The resources required to treat the prevalent disorders were considerable and differences between dentate and edentulous people were negligible. Senior citizens expressed attitudes which indicate that they value dental health and would like help to achieve it. PMID- 2331649 TI - Results of the socio-dental survey of people aged 50 and older living in East York, Ontario. AB - We determined the oral health status and treatment needs of the current and future elderly in East York and tested four enrollment strategies for community based surveys. We selected our sample from the Municipal Composite Report and obtained the data using a multi-item questionnaire and a clinical examination. The examination protocol was based on World Health Organization (WHO) methodology but was expanded to provide tooth surface specific information. Of those contacted by telephone and repeated mailings, 35% participated. The sample appeared representative of the community as determined by a follow-up mail survey of non-respondents. 76% of those examined were dentate and 71% had visited the dentist within the last two years. Nonetheless, 27% had chewing impairment, 15% had discomfort with their teeth and 15% needed care urgently. Treatment needs were highest for the 187 dentate. They required 504 extractions or restorations and 113 denture services. Periodontal care for calculus and pockets was needed by 86% of the dentate. This report shows an apparent contradiction of high dental treatment needs remaining in the context of reported high care-seeking rates. PMID- 2331650 TI - Knowledge, values, attitudes and behavioural intent of Nova Scotia nurses toward AIDS and patients with AIDS. AB - To assess the knowledge, values, attitudes and behavioural intent of Nova Scotia nurses toward AIDS and patients with AIDS, questionnaires were sent to a random sample of 400 general duty nurses. Analysis of the 179 returned questionnaires (45%) showed that although 88% of the nurses indicated that they intended to nurse patients with AIDS, the quality of the nursing care might be inadequate because (1) there was lack of knowledge about AIDS, especially outside urban Halifax; (2) half the nurses were undecided and 10% were very negative toward homosexuals and patients with AIDS; (3) although nurses perceived staff in hospital as reflecting positive attitudes toward care of patients with AIDS, those closest to the nurse (spouse, family and friends) were perceived as negative to her caring for patients with AIDS; and (4) nurses found media sources of information about AIDS more helpful than professional sources. PMID- 2331651 TI - Knowledge, attitudes, beliefs and practices related to AIDS among Montreal residents of Haitian origin. AB - We used interviews of 268 subjects to ascertain knowledge, attitudes, beliefs and practices related to AIDS among Montrealers of Haitian origin, from November 1987 through October 1988. The questions on knowledge included items on general knowledge about the disease (prevention of AIDS, treatment, nature and manifestations of the disease, screening and high-risk groups), and more specific questions about modes of HIV-1 transmission. The average correct answers to questions on general knowledge about AIDS was 81%. The questions on HIV-1 transmission concerned both modes of infection that are scientifically established, and other modes that are not scientifically recognized. The average correct answers to questions on scientifically recognized modes of infection was 94% and the average correct answers for modes of transmission that are not scientifically accepted was 74%. The attitudes and beliefs of Montrealers of Haitian origin toward persons with AIDS was only moderately favourable. Attitudes and beliefs toward condom promotion were very positive. The percentage of subjects reporting male homosexuality or injection drug use was extremely small. 23% of subjects who had experienced sexual intercourse reported that they had two or more partners during the 12 months preceding the survey. PMID- 2331652 TI - A survey of knowledge and attitudes with regard to AIDS among grade 7 and 8 students in Ottawa-Carleton. AB - With parental consent, we surveyed 942 students in grade 7 and 8 at the Ottawa Board of Education before the introduction of compulsory AIDS education. Television was seen as the most common and credible source of information about AIDS. Parents (by girls) and school nurse (by boys) were also seen as credible sources of information about AIDS. Boys seemed to know more about the transmission of AIDS than girls did. There was high awareness of condoms as an effective method of preventing the spread of AIDS. Avoidance of sexual intercourse as an effective preventive measure was less well known. AIDS education in school should emphasize abstinence as well as barrier methods as effective methods in preventing AIDS, and utilize the media, parents and family in educating students about AIDS. PMID- 2331654 TI - Sex education and the prevention of STD/AIDS and pregnancy among youths. AB - The prevention of unwanted pregnancy and STD/AIDS are two major goals of health educators. Usually these are discussed as separate goals. In this paper both of these health concerns are presented from a behavioural preventive perspective. Our objective is to outline the essential components to be used by health educators in school-based sex education programs focussing on the prevention of unwanted pregnancy and STD/AIDS. PMID- 2331653 TI - Knowledge, attitudes and behaviours related to AIDS among first-year university students. PMID- 2331655 TI - Hib vaccine coverage in children attending day care/nursery school in East York. AB - This survey assessed Haemophilus influenzae b vaccine coverage and factors affecting compliance in children at increased risk. A telephone survey was conducted of a random sample of 75 children, aged 24-60 months, attending licensed day care/nursery schools in East York. 96% of the sample was surveyed; only 51% were vaccinated. Older children were less likely to be immunized and there were more single-parent families among the non-vaccinated. The age, educational level and country of birth of the parents and the number of siblings were not associated with vaccination status. In 20% of the non-vaccinated group, concern about side effects was the main reason for non-compliance. For 91%, a factor of "moderate/very much concern" was the perceived unimportance of preventing Haemophilus influenzae b illness. Education for parents and physicians, special programs aimed at risk groups, and consideration of mandatory immunization against Haemophilus influenzae b in children attending day care/nursery schools are needed. PMID- 2331656 TI - Hepatitis B control in Toronto classrooms for the mentally retarded: a seroprevalence survey. AB - A seroepidemiologic hepatitis B survey of students and staff at schools for the mentally retarded in the City of Toronto found 2.5% of students to be carriers, 5% to be immune without being immunized, 11.3% to have immunization underway or complete, and 81.2% to be susceptible. The first two groups were older and more likely to have been born in countries with intermediate or high hepatitis B marker prevalence. Among staff tested, 4.1% were immune without immunization while all others were susceptible. Because hepatitis B control recommendations could not be made on the basis of these results alone, local Medical Officers of Health also considered other studies and practical experience to recommend the following: (1) Use Ontario Ministry of Health Guidelines for mentally retarded hepatitis B carriers in regular schools; (2) Offer hepatitis B vaccine to all susceptible students and staff in schools specifically for the mentally retarded. PMID- 2331657 TI - Cancer incidence in an urban community: an historical cohort study. AB - This historical cohort study tested the hypothesis that residents of an industrialized urban community were at higher risk of cancer than residents of a comparable, but non-industrialized, community. The exposed (C1) and the unexposed (C2) cohorts resided in their respective neighbourhoods between 1952 and 1956. All incident cancers were identified through linkage with the Ontario Cancer Registry for 1964-1982. Cancer incidence rates in the two cohorts were 7.0 and 7.3 per 1,000 person-years, respectively. Relative risk estimates for all cancers, lung cancer and cancers associated with environmental exposure, were not significantly different from 1.0. Only colorectal cancers were significantly more frequent in the C1 than the C2 cohort, and these only in one sub-analysis. Overall, we conclude that if there was increased risk of cancer related to environmental pollution in the industrially exposed community, it was less than a two-fold increase. PMID- 2331658 TI - Smoking cessation in Nova Scotia: results of the Time to Quit program. PMID- 2331659 TI - The relationship of physical activity to alcohol consumption in youth, 15-16 years of age. PMID- 2331660 TI - Estimation of hospital bed availability. PMID- 2331661 TI - Sources of dioxins and furans in British Columbia. AB - A recent Canadian study of the levels of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in adipose tissue suggested higher levels in British Columbians than in other Canadians. This led to concerns about the sources of these compounds in B.C. In this paper, we review scientific publications to generate a list of possible sources of PCDDs and PCDFs. We outline which of these are likely to be found in British Columbia, and develop hypotheses concerning their potential contribution to an individual's "PCDD/PCDF load". Further sampling and analysis of British Columbians' adipose tissue could test hypotheses about occupational and environmental exposures to dioxins and furans. PMID- 2331662 TI - Geriatric clinical pharmacology. AB - Geriatric medicine and clinical pharmacology have important areas of common interest, and the present volume is an expression of this. The role of geriatric clinical pharmacology is to improve drug treatment in the elderly; this role can only be realized if there is adequate funding and if those involved are prepared to play a comprehensive role, not only in research but also in patient care and as educators. PMID- 2331663 TI - Compliance in the elderly. AB - Noncompliance is not a unique phenomenon associated with aging. Many of the same problems concerning taking medications most appropriately apply to 40 year olds as well as to 80 year olds. What is unique about the elderly is their greater sensitivity to medications, their greater propensity for the development of adverse effects, and the greater complexity of their regimens as they develop chronic illnesses through the course of their lives. In addition, decreasing acuity of special senses, problems with memory, and the interposition of other caregivers are all unique phenomena that have to be dealt with through expansion of the standard methods but only rarely through specific methods. Utilization of modern technology such as video cassette recorders, large print reproductions, and improved communication modalities for people with hearing and sight disabilities may overcome some of the problems leading to decreased comprehension and communication ability in elderly patients. Similarly, for those with financial barriers to appropriate utilization of medications, programs such as the Elderly Pharmaceutical Insurance Coverage (EPIC) in New York State may be helpful. Medicaid and AARP programs for obtaining medications at lower prices can help financially strapped patients. The necessity for physicians to learn about cultural attitudes toward family and governmentally supplied caregivers may also facilitate optimal medication utilization in our polycultural society. Medications can serve the elderly to great benefit. Misapplication and misuse of medications may result in undesirable outcomes, ranging from lack of maximum efficacy, annoying nuisance side effects, diminishing quality-of-life, and even life-threatening adverse outcomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331664 TI - Surviving summer camp. PMID- 2331665 TI - Accidental killers. PMID- 2331666 TI - Promoting healthy hearts. PMID- 2331667 TI - Nursing in Nigeria. PMID- 2331668 TI - New brand, familiar strategy. PMID- 2331669 TI - Continuous subcutaneous infusion of narcotics. CSCI. PMID- 2331670 TI - Teaching teenagers about AIDS. PMID- 2331671 TI - [Training for working with the dying]. AB - A doctoral thesis, recently defended at the University of Caen in France, is discussed here. This descriptive study looks at the question of training individuals to accompany the dying patient, and the abilities, qualifications and skills that are required. PMID- 2331672 TI - [Neuromuscular disorders]. AB - In this study, the author focuses on three neuromuscular disorders that have historically been isolated to a specific region in Quebec. The author is convinced that appropriate nursing interventions can help in the detection of these disorders and can, using data on social behavior, help eliminate harmful genetic mutations. PMID- 2331673 TI - Physical mapping of the human chromosome 11q23 region containing the ataxia telangiectasia locus. AB - Two breakpoints within chromosome 11q23 were characterized with 29 DNA probes to establish a physical map of the region. This region is notable in that it contains at least 14 functional genes which are also syntenic in the mouse (chromosome 9). Chromosome 11q23 includes these markers: STMY, CLG, NCAM, DRD2, APOA1, APOC3, APOA4, CD3E, CD3D, CD3G, PBGD, THY1, ets-1, and cbl-2. The two breakpoints, herein called "X;11" and "4;11," defined a region of approximately 8 cM containing the APO and CD3 complexes as well as the polymorphic marker D11S29. DRD2 localized centromeric to the X;11 breakpoint despite evidence for close genetic linkage to D11S29, suggesting that DRD2 lies close to the X;11 breakpoint. THY1, PBGD, and cbl-2 localized telomeric to the 4;11 breakpoint and thus to the [D11S29--APO--CD3] grouping as well. The physical map helps to correlate the cytogenetic and linkage maps of this region. It also suggests that the human 11q23 syntenic grouping is inverted with respect to its murine counterpart. Based on this physical map and on our primary linkage map of the 11q23 region, we are able to confirm a preliminary localization of the gene for ataxia-telangiectasia group A (ATA) to a region centromeric to the interval defined by D11S144 (pYNB3.12) and THY1. PMID- 2331674 TI - Use of conditioned media in cell culture can mask cytogenetic abnormalities in acute leukemia. AB - Conditioned media (CM) from a human lung adenocarcinoma cell line expressing interleukins 1 and 6 (IL-1, IL-6), granulocyte (G), macrophage (M), and GM colony stimulating factors (G, M, GM-CSF) and transforming growth factor beta (TGF beta) were used to stimulate growth of bone marrow (BM) cells from 18 persons with leukemia, myelodysplastic syndrome, or lymphoma. The objective was to increase numbers of analyzable metaphases and to enhance the likelihood of detecting cytogenetic abnormalities. Although more mitotic cells were observed with CM, the detection rate of cytogenetic abnormalities decreased in 12 of 18 cases. These data indicate that use of CM for cytogenetic analyses may favor growth of normal versus leukemia cells and mask cytogenetic abnormalities. PMID- 2331675 TI - Spontaneous remission in myelodysplastic syndrome. A case report. AB - A patient with refractory anemia with excess blasts (RAEB) and pancytopenia is reported. He was red blood cell (RBC)-transfusion dependent. Karyotype analysis showed a complex cytogenetic abnormality consisting of loss of chromosome 7 and trisomy 8. Without cytotoxic treatment, his complete blood count (CBC) subsequently became normal. He is no longer transfusion dependent and repeat cytogenetic analyses are normal. PMID- 2331676 TI - 5q deletion. The sole chromosome change in a carcinoma of the bladder. AB - Direct chromosome preparations of a transitional cell carcinoma of the bladder that had invaded the mucosa but not more deeply showed a 46,XY,5q- karyotype in nearly all metaphases. This is the first description of a 5q deletion, which may have been interstitial, del(5)(q13q22), as the only change in a bladder carcinoma. PMID- 2331677 TI - Genetic linkage and physical mapping of a cancer gene. Ataxia-telangiectasia. PMID- 2331678 TI - Chromosome 3 and 12p rearranged in a well-differentiated peritoneal mesothelioma. PMID- 2331679 TI - A procedure for carrier detection in ataxia-telangiectasia. PMID- 2331680 TI - A case of renal lymphangioma with a karyotype 45,X,-X,i dic(7q). AB - Cytogenetic analysis of a polycystic unilateral renal lymphangioma was performed by short-term culture and banding methods. The tumor's cells showed an isochromosome of the long arm of chromosome #7 and monosomy of X chromosome, whereas the peripheral lymphocytes stimulated with phytohemagglutinin showed a normal female karyotype, 46,XX. These karyotypic anomalies suggest that lymphangioma, although clinically benign, may have malignant potential. PMID- 2331681 TI - Chromosomal patterns in Warthin's tumor. A second type of human benign salivary gland neoplasm. AB - The cytogenetical observations in eight successfully cultured human adenolymphomas are reported. When the results were considered with those of two previously reported cases, three main stemline groups could be distinguished: (a) one with a normal karyotype and noted as a primary or secondary stemline in all hitherto studied tumors; (b) a second group with only numerical changes, either loss of the Y chromosome or trisomy or monosomy 5; and (c) a third group with only structural changes, as a rule with one or two reciprocal translocations. With regard to the last group, studies of many more cases are necessary to decide whether distinctive subgroups exist. Analyses using molecular methods are also urgently needed to clarify whether the normal stemline cells contain submicroscopic changes. PMID- 2331682 TI - Cytogenetic studies of endometrial malignancies. AB - Thirty cases of endometrial malignancy were successfully studied cytogenetically. Twenty-four of the cases were endometrial adenocarcinomas. Twenty-three of these were stage I tumors, and the twenty-fourth was a stage IV tumor. Fourteen of the stage I adenocarcinomas had abnormal chromosomes, and nine had apparently normal chromosomes. No two tumors had an identical chromosomal rearrangement. Trisomy 1q was common however; 10 of the 14 tumors with abnormal chromosomes had a chromosome 1 abnormality. Clinical and pathologic data were available for 17 of these patients. There appeared to be no relationship between prognostic indicators and the tumor karyotype except for uterine size. Six cases of endometrial malignant mixed mullerian tumor (MMMT) of the homologous type were also analyzed cytogenetically. Three of these tumors had very abnormal karyotypes, and the remaining three had apparently normal chromosomes. Structural abnormalities of chromosome 1, 3, and 5 were present in all three tumors with abnormal karyotypes, but identical breakpoints or rearrangements were not observed. PMID- 2331683 TI - Pleomorphic adenomas with unbalanced chromosomal abnormalities have an increased in vitro lifetime. AB - The in vitro lifetime of 100 salivary gland pleomorphic adenomas was investigated. On the average, they had a limited lifetime of 3.7 passages. In 86 cases, the tumors were successfully karyotyped, resulting in three major cytogenetic subgroups characterized by either an apparently normal karyotype or by rearrangements of 8q12 or 12q13-15. There was no significant difference between the in vitro lifetime of the tumors with a normal or with an aberrant karyotype. The three adenomas with the longest lifetime were characterized by an unbalanced karyotype. One of them had a deleted chromosome 6, which has also been described in malignant tumors. An increased in vitro lifetime may thus correspond to early steps of malignant transformation in vivo and can be caused by additional unbalanced chromosome aberrations. In the future, long-term cultivation can be helpful in defining chromosomal regions involved in this process. PMID- 2331684 TI - Complex karyotypic anomalies, including an i(5p) marker chromosome, in malignant mixed mesodermal tumor of the ovary. AB - Cytogenetic analysis of short-term cultures initiated from an ovarian malignant mixed mesodermal tumor yielded the following karyotype: 59-61, XX,t(1;?)(p36;?), +t(1;9) (q43;q21), +t(2;?)(p25;?), +i(5p), +i(5p), +7, +t(7;?)(p13;?), +8,der(11) (pter----cen----q23::q13----q23::q13----q23::?), +12, + der(13)t(13;15)(q21;q15), -15,der(16) (16qter----cen----16p13::hsr::8q21----8qter), +19, + der(20)t(X;20)(q13;p13), -22, +4 - 6mar. Because the only other cytogenetically characterized ovarian neoplasm of this rare histopathologic subtype also had a small metacentric marker interpreted as an isochromosome for the short arm of a B group chromosome, we suggest that i(5p) constitutes a nonrandom anomaly in mixed mesodermal tumors. PMID- 2331685 TI - Cytogenetic analysis of a cell line established from a Krukenberg tumor. AB - Cytogenetic analysis was performed on a cell line, designated KS1, derived from a Krukenberg tumor. A modal chromosome number of 60-65 chromosomes was present, as were several clonal chromosome rearrangements involving, among others, chromosomes 2, 3, 6, 9, 11, 12, and 22. Ten to 30 double minutes were present in most cells. PMID- 2331686 TI - Cytogenetics of carcinoma in situ of the testis. AB - Carcinoma in situ (CIS) of the testis is the precursor lesion of most testicular germ cell tumors (TGCTs). Karyotyping of CIS is important for a better understanding of the pathogenesis of TGCTs and the progression to invasive cancer. We karyotyped three cases of CIS. All three cases showed a numerical abnormal chromosomal pattern. In one case, two copies of the germ cell tumor marker i(12p) were found. PMID- 2331687 TI - Complex translocations in a patient with chronic myelocytic leukemia: t(9;22;17) and t(10;18;19) after two failed bone marrow transplantations. AB - A 6-year-old white boy with chronic myelogenous leukemia (CML) (adult type) developed complex translocations after a bone marrow transplant (BMT): t(9;22;17)(q34;q11;p12) t(10;18;19)(p11;q11;p12) and in the accelerated phase. The patient relapsed after his BMT and underwent a second BMT after a documented blast crisis. The previous karyotypic translocations persisted. PMID- 2331688 TI - Trisomy 3 in cold agglutinin disease. AB - Cold agglutinin disease (CAD) is a form of autoimmune hemolytic anemia generally considered to result from an antibody-producing clonal expansion of B lymphocytes. We studied 16 patients with CAD and demonstrated a chromosomally abnormal clone in the peripheral blood (PB) of six. Trisomy 3 was the only abnormality in two patients, trisomy 12 the only abnormality in one, and both trisomy 3 and trisomy 12 were present in three patients. A lymphoma was subsequently diagnosed in two of these six patients and in none of the patients without a karyotypic abnormality. The results suggest that trisomy 3 confers a slight growth advantage in the B-cell lineage, particularly at a relatively late stage of differentiation. The resultant clone may present clinically as CAD and, in some cases, progress to a clinical lymphoma. PMID- 2331689 TI - Chromosome abnormalities involving heterochromatic regions in monocytic leukemia. AB - We report two cases of monocytic leukemia associated with cytogenetic changes involving the juxtacentromeric heterochromatin of different chromosomes. In a patient with chronic myelomonocytic leukemia (CMMoL) we describe a translocation t(1;9)(q12;q13) in which the duplicated derivative chromosome 9q + showed a huge centromeric C-band, derived by fusion of the heterochromatic regions of chromosomes 1 and 9. The constitutional karyotype showed two heterochromatin polymorphisms, 1qh + and inv(9qh). In the second case, an acute monoblastic leukemia was associated with an abnormally elongated juxtacentromeric heterochromatic region of chromosome 4 that was not constitutionally present. PMID- 2331690 TI - Factors related to practice of breast self-examination in rural women. AB - The purpose of this study was to examine variables related to breast self examination (BSE) in rural women. The sample of convenience consisted of 347 women who were members of selected county-extension homemaker clubs. Champion's Health Belief Model Scale was used to measure susceptibility, seriousness, benefits, barriers, health motivation, sociodemographics, and knowledge variables and frequency of BSE. Multiple regression analysis indicated that the Health Belief Model concepts accounted for 26% of the variance in BSE practice. Women who perceived more benefits of BSE in reducing the severity of breast cancer were more likely to report more frequent BSE. Women who perceived fewer barriers to performing BSE and those who scored high on health motivation were also more likely to report performing monthly BSE. Pearson product-moment correlation indicated a significant positive relationship between the variables of BSE knowledge and BSE practice (r = 0.1216; p = 0.023). The lambda statistics showed weak or no association between the demographic variables of age, race, marital status, religion, education, personal experience with breast disease, and friend's experience with breast disease and BSE practice. These findings suggest that perhaps educational programs emphasizing benefits of BSE may be implemented for women represented in this sample in an attempt to increase the number of women practicing BSE. Assessment of women's perceptions of potential barriers would allow nurses to plan appropriate strategies that could reduce the barriers. Finally, assessment of women's general health practices may identify women motivated toward good health. These women may be likely to complete monthly BSE if encouraged to do so. PMID- 2331691 TI - Defining the content domain of quality of life for cancer patients with pain. AB - This study identified attributes that define the content domain of quality of life in a sample of 41 cancer patients with chronic pain. Patients were asked four open-ended questions about the meaning of quality of life, what contributes to a good or poor quality of life, and how pain influences quality of life. Content analysis of responses revealed three categories of attributes that embrace the quality-of-life content domain. The first category is physical well being. It includes general functioning and disease/treatment-specific attributes. The second is psychological well-being. It includes affective-cognitive attributes, coping ability, meaning of pain and cancer, and accomplishment attributes of quality of life. The third is interpersonal well-being. It incorporates social support and social/role functioning attributes. Replications of the current study in other groups of patients may yield data to support a two part, multidimensional quality-of-life instrument. A norm-referenced measure can be used to evaluate quality of life in terms of attributes that are salient regardless of the disease or treatment. A domain-referenced measure may be used to evaluate attributes whose salience is dependent on specific disease, treatment, or life events. PMID- 2331692 TI - Hospice nursing. Present perspectives and future directives. AB - The specialty of hospice nursing calls for a highly skilled and knowledgeable practitioner. Four categories emerge to define and describe a specialist in hospice/palliative care nursing as one who practices: (a) intensive "caring"--the management of physical, psychological, social, and spiritual problems of dying persons and their families; (b) collaborative sharing--the coordinated and collaborated efforts of the extended and expanded components of hospice care services; (c) continuous knowing--the acquisition of the counseling, managing, instructing, "caring," and communicating skills/knowledge required for the specialty of hospice nursing; and (d) continuous giving--the balance of the hospice nurse's own self-care needs with the complexities and intensities of death and dying. To provide skilled, competent hospice nursing, two levels of hospice education are proposed, and descriptions are given for (a) the "hospice nurse certified (HNC)" who delivers competent, expert, and continuous patient/family care; and (c) the "hospice nurse advanced (HNA)" who provides educational needs and administers hospice care programs. Within the expanded and extended components of hospice care, the nurse works with an interdisciplinary team to provide care that is humanistic and supportive, and that is continuous and comprehensive. PMID- 2331693 TI - A core curriculum for a postbasic course in cancer nursing. The European Oncology Nursing Society. PMID- 2331694 TI - Management of radiation-induced moist skin desquamation using hydrocolloid dressing. AB - Moist skin desquamation has been of concern to radiation oncologists, nurses and patients since the inception of this mode of therapy. As radiation treatment machines became more sophisticated, severe reactions became less of a problem. However, with the increasing use of chemotherapy and radiation as combined modalities, moist skin reaction is occurring with greater frequency. A noncomparative study of 20 patients using a hydrocolloid occlusive dressing (Duoderm) was initiated. The purpose of the study was to determine whether moist occlusive healing would be beneficial. The dressing was evaluated on the basis of healing time, safety, wound temperature, bacterial growth, and comfort. Data were collected using photographs, bacterial cultures, temperature probes, and patient evaluations. Eighteen patients completed the study. All patients' skin reactions healed. There were no wound infections evident. Mean healing time was 12 days, with mean wound temperature relative to body core -0.8 degree C on day 1 and -1.2 degrees C on the healed site. Patient results on comfort were: 8 of 18 excellent, 7 of 18 good, 3 of 18 fair, and 0 of 18 poor. The results of this study indicate that a hydrocolloid occlusive dressing can be effective in the healing process of moist skin reaction that is due to radiation therapy. PMID- 2331695 TI - Patients' perceived knowledge and learning needs concerning radiation therapy. AB - The purpose of this study was to determine overall differences between two age groups of patients with cancer in their perceived knowledge and perceived learning needs about radiation treatment and to determine differences between perceived knowledge and perceived learning needs within each age group. A total of 40 subjects between the ages of 25 and 59 years and 40 subjects aged 60 years and older answered two questionnaires. The questionnaires were derived from the Assessment of Learning Needs: Oncology Instrument and are referred to in this study as Radiation Therapy Subscale I and Radiation Therapy Subscale II. Differences between the younger group and the older group were not statistically significant. Results did indicate that members of the younger group perceived themselves to know more about their radiation therapy than did older group members. However, patients within each age group perceived themselves to have more knowledge than learning needs. Results of this study suggest that the two age groups demonstrated no significant age-related differences in responding to the questionnaires. PMID- 2331696 TI - Informational and psychosocial needs of women choosing conservative surgery/primary radiation for early stage breast cancer. AB - Recent advances in the treatment of early stage breast cancer give women a choice of treatments. Prospective and retrospective studies demonstrate the comparable efficacy of treatment with a modified radical mastectomy and treatment with conservative surgery and primary radiation. While the number of women with early stage breast cancer choosing the latter treatment continues to increase, there is a paucity of information in the nursing literature assessing the informational and psychosocial needs of this group. This article reports the results of a questionnaire assessing the informational and psychosocial needs of patients choosing breast conservation surgery, and the future implications of these results for the nursing profession. PMID- 2331697 TI - A framework for studying functional status after diagnosis of breast cancer. AB - This article presents a framework for studying changes in and variables associated with functional status after diagnosis of breast cancer. Functional status is defined as the woman's performance of activities related to her possible multiple roles of spouse, parent, homemaker, community member, and worker. Roy's Adaptation Model of Nursing serves as the overall conceptual model. A review of the research literature provides support for relationships linking psychological state, interpersonal relationships, immune status, treatment regimen, severity of disease, and demographic factors with functional status. PMID- 2331698 TI - Solid-phase synthesis of a cell-wall component of Haemophilus (Actinobacillus) pleuropneumoniae serotype 2. PMID- 2331699 TI - Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences. AB - The 1H-n.m.r. 3J values for the L-iduronic acid (IdoA) residues for solutions in D2O of natural and synthetic oligosaccharides that represent the biologically important sequences of dermatan sulfate, heparan sulfate, and heparin have been rationalized by force-field calculations. The relative proportions of the low energy conformers 1C4, 2S0, and 4C1 vary widely as a function of sequence and of pattern of sulfation. When IdoA or IdoA-2-sulfate units are present inside saccharide sequences, only 1C4 and 2S0 conformations contribute significantly to the equilibrium. This equilibrium is displaced towards the 2S0 form when IdoA-2 sulfate is preceded by a 3-O-sulfated amino sugar residue, and towards the 1C4 form when it is a non-reducing terminal. For terminal non-sulfated IdoA, the 4C1 form also contributes to the equilibrium. N.O.e. data confirm these conclusions. Possible biological implications of the conformational flexibility and the counter-ion induced changes in conformer populations are discussed. PMID- 2331700 TI - Conformation of the pentasaccharide corresponding to the binding site of heparin for antithrombin III. AB - The conformation in solution of the pentasaccharide methyl glycoside (As-G-A*-Is AM; 1), which represents the binding site of heparin for Antithrombin III, has been investigated using molecular mechanics and 1H-n.m.r. spectroscopy. The pentasaccharide has a rather rigid (As-G-A*) and a more flexible (Is-AM) region. A simplified model of 1, comprising two conformations, corresponding to the 1C4 and the 2S0 forms of the iduronate residue, and modified at the G-A* glycosidic linkage with respect to the energy minimum, reproduces most of the observed 3J values and n.O.e. enhancements. The possible role in the binding to Antithrombin III of a low-energy conformer, not observed in solution, is discussed. PMID- 2331701 TI - Conformational features of C-glycosyl compounds: crystal structure and molecular modelling of "methyl C-gentiobioside". AB - The crystal of "methyl C-gentiobioside" (methyl 8,12-anhydro-6,7-dideoxy-D glycero-D-gulo-alpha-D-gluco-trideca pyranoside) (C14H26O10) is triclinic, space group P1, with a = 1.0181 (6) nm, b = 0.8093 (5) nm, c = 0.5066 (4) nm, alpha = 96.03 (5) degrees, beta = 99.94 (5) degrees, gamma = 90.85 (5) degrees. The two D glucose residues have the 4C1 conformation. The orientation of the beta-(1----6) linkage is characterized by torsion angles phi = 55.9 degrees, psi = 175.1 degrees, and omega = -63.9 degrees. The orientation of the primary hydroxyl group at the non-reducing residue is gauche-trans (omega' = -53.6 degrees). There is no intramolecular hydrogen bond. Molecules are held together by a network of hydrogen bonds involving all of the hydroxyl groups. This crystal structure is the first experimental characterization of a "C-disaccharide". Unlike methyl gentiobioside, which has a high level of conformational flexibility, the "C disaccharide" has a restricted flexibility. Each of the low-energy conformers in vacuo has a value of phi centered about 60 degrees, in agreement with the solid state conformation, and the exo-anomeric effect is no longer predominant. PMID- 2331702 TI - Total synthesis of the mollu-series glycosyl ceramides alpha-D-Manp-(1----3)-beta D-Manp-(1----4)-beta-D-Glcp-(1----1)-Cer and alpha-D-Manp-(1----3)-[beta-D-Xylp (1----2)]-beta-D-Manp-(1----4)-beta- D-Glcp-(1----1)-Cer. AB - The mollu-series glycosphingolipids, O-alpha-D-mannopyranosyl-(1----3)-O-beta-D mannopyranosyl-(1----4)-O-bet a-D-glucopyranosyl-(1----1)-2-N-tetracosanoyl-(4E) sphingeni ne and O-alpha-D-mannopyranosyl-(1----3)-O-[beta-D-xylopyranosyl-(1--- 2])-O- beta-D-mannopyranosyl-(1----4)-O-beta-D-glucopyranosyl-(1----1)-2-N- tetracosanoyl-(4E)-sphingenine, were synthesized for the first time by using 2,3,4-tri-O-acetyl-D-xylopyranosyl trichloroacetimidate, methyl 2,3,4,6-tetra-O acetyl-1-thio-alpha-D-mannopyranoside, benzyl O-(4,6-di-O-benzyl-beta-D mannopyranosyl)-(1----4)-2,3,6-tri-O-benzyl-be ta-D- glucopyranoside 9, and (2S,3R,4E)-2-azido-3-O-(tert-butyldiphenylsilyl)-4-octade cene-1,3-diol 6 as the key intermediates. The hexa-O-benzyl disaccharide 9 was prepared by coupling two monosaccharide synthons, namely, 2,3-di-O-allyl-4,6-di-O-benzyl-alpha-D mannopyranosyl bromide and benzyl 2,3,6-tri-O-benzyl-beta-D-glucopyranoside. It was demonstrated that azide 6 was highly efficient as a synthon for the ceramide part in the coupling with both glycotriaosyl and glycotetraosyl donors, particularly in the presence of trimethylsilyl triflate. PMID- 2331703 TI - Synthesis of 3-amino-2,3,6-trideoxy-2-fluoro-L-talose and -D-allose [(R)-2-fluoro L-daunosamine and (R)-2-fluoro-D-ristosamine]. AB - The title compounds were synthesized (as methyl glycosides) starting from 1,3,4,6 tetra-O-acetyl-2-deoxy-2-fluoro-beta-D-glucopyranose. Stereoselective methods of glycosylation gave, via the tri-O-acetylglycopyranosyl bromide, the methyl 2 deoxy-2-fluoro-alpha- and -beta-D-glucopyranoside triacetates. Each anomer was O deacetylated and further transformed into the corresponding, 4,6-O-benzylidenated 3-triflate, and the triflates were converted by azide displacement into the 3 azido-2,3-dideoxy-2-fluoroglycosides having the D-allo configuration. Hanesssian Hullar reaction then furnished the corresponding 6-bromo-6-deoxy-4-benzoates, which were dehydrobrominated to give the methyl 3-azido-4-O-benzoyl-2,3,6-tri deoxy-2-fluoro-alpha- and -beta-D-ribo-hex-5-enopyranosides. Debenzoylation of the alpha-anomer, followed by catalytic hydrogenation, led to methyl 3-amino 2,3,6-trideoxy-2-fluoro-beta-L-talopyranoside [methyl (R)-2-fluoro-beta-L daunosaminide], whereas the same sequence applied to the beta-anomer afforded methyl 3-amino-2,3,6-trideoxy-2-fluoro-beta-D-allopyranoside [methyl (R)-2-fluoro beta-D-ristosaminide]. The overall yields for these 10-step sequences were 11-12 and 16%, respectively. The 1H- and 13C-n.m.r. data for the new fluoro sugar derivatives are discussed with respect to the dependence of JF,H and JF,C values on molecular geometry and substituent effects. PMID- 2331704 TI - Biodegradation of oxidized regenerated cellulose. AB - The in vitro solubilization and degradation of regenerated cellulose was studied under conditions which approximate those found in vivo, when the material is used as an adhesion barrier to assist normal wound repair. Factors affecting solubilization which were examined included the effects of serum or plasma, and the presence of hydrolytic enzymes. Products of the solubilization and degradation processes were examined by high performance liquid chromatography coupled with pulsed amperometric detection. The oxidized polymer readily undergoes chain shortening to give oligomers which, in the presence of plasma or serum, are further hydrolyzed to smaller fragments, including glucuronic acid and glucose. Proposed mechanisms of degradation are discussed. PMID- 2331706 TI - Nurses as leaders: taking charge of our future. PMID- 2331705 TI - The structure of the asparagine-linked sugar chains of bovine brain ribonuclease. AB - The asparagine-linked sugar chains of bovine brain ribonuclease were quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis. After N-acetylation, they were converted into radioactively labeled oligosaccharides by NaB3H4 reduction. The radioactive oligosaccharide mixture was fractionated by ion-exchange chromatography, and the acidic oligosaccharides were converted into neutral oligosaccharides by sialidase digestion. The neutral oligosaccharides were then fractionated by Bio-Gel P-4 column chromatography. Structural studies of each oligosaccharide by sequential exoglycosidase digestion in combination with methylation analysis revealed that bovine brain ribonuclease showed extensive heterogeneity. It contains bi- and tri antennary, complex-type oligosaccharides having alpha-D-Manp-(1----3)-[alpha-D Manp-(1----6)]-beta-D-Manp -(1----4)-beta-D- GlcpNAc-(1----4)-[alpha-L-Fucp-(1--- 6)]-D-GlcNAc as their common core. Four different outside oligosaccharide chains, i.e., beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----, alpha-Neu5Ac-(2----6)-beta-D- Galp-(1----4)-beta-D-GlcpNAc-(1----, alpha-Neu5Ac-(2----3)-beta-D-Galp-(1----4)- beta-D-GlcpNAc-(1----, and alpha-D-Galp-(1----3)-beta-D-Galp-(1----4)-beta-D GlcpNAc-(1----, were found. The preferential distribution of the alpha-D-Galp-(1- --3)-beta-D-Galp-(1----4)-beta-D-GlcpNAc group on the alpha-D-Manp-(1----6) arm is a characteristic feature of the sugar chains of this enzyme. PMID- 2331708 TI - Nursing care of the angry terminal patient a challenge. PMID- 2331707 TI - Health care: a right--not a privilege. PMID- 2331709 TI - [The goals, types and criteria of health care]. AB - To assess correctly the targets of health care is a difficult and responsible task. A valuable example of the targets, methods and criteria of health care is the programme of the World Health Organization "Health for All by the Year 2000". The author explains its structure and time schedule individual groups of tasks. The programme should become the basis of a nation-wide effort leading to the improvement of the health status of the population. PMID- 2331710 TI - [Trends in lipid consumption in the Czechoslovak population]. AB - The health status of our population is not satisfactory, an important part in this respect is played among others also by nutrition. The authors submit information on changes in the energy, protein and fat consumption of the Czechoslovak population during the period between 1936 and 1987. The increase in fat consumption is due in the first place to the increased consumption of meat, milk, eggs and fats. While in 1936 the mean consumption was 79.0 g of fat per head per day, in 1987 the intake was more than 129 g, i.e. by 63% higher. In addition to fats the greatest contribution to fat intake is made by meat and meat products (40%), milk and dairy products (18%) and cereal products (13%). The increase in lipid consumption is one of the risk factors participating in the development of cardiovascular diseases, the trend of which is alarming. Improvement can be achieved by a change of dietary habits; the prerequisite is a nation-wide programme with an active approach in all spheres--from farmers, the food industry and commerce to all types of communal and family catering. PMID- 2331711 TI - [Incidence of systemic hypertension after orthotopic heart transplantation]. AB - In a group of 18 patients after orthotopic transplantation of the heart (OTH) operated, 4-56 months previously and treated by combined immunosuppression (Cyclosporin A, corticoids, azathioprine), systemic hypertension was revealed in six and borderline hypertension in three patients. The mechanism of the development of hypertension, after OTH has not been elucidated. As to the circadian rhythm of the blood pressure, as compared with normotensive subjects and patients with essential hypertension, in patients after OTH usually the drop of systemic pressure values does not occur during the night; on the contrary the blood pressure rises during the night. This finding may be due to denervation of the heart after OTH and an abnormal response of baroreceptors to the rise of blood pressure; in this the effect of corticoids may also participate. After a one-year interval the abnormal reaction of the systolic pressure remains preserved, while the 24-hour profile of the diastolic pressure has trend towards normalization. PMID- 2331712 TI - [Bezalip in the treatment of hyperlipoproteinemia]. AB - In a specialized clinic for hyperlipoproteinaemias 15 patients with different types of hyperlipoproteinaemias were treated with bezafibrate (Bezalip R tablets a 200 mg of Boehringer Co.) for a period of four weeks 3 X 1 tablet per day. The administration of Bezalip led to a significant drop of cholesterol (-20%), triglycerides by 40% and LDL-cholesterol (-17%), while the HDL cholesterol level did not change significantly. During treatment a drop of the apolipoprotein B level by 17% occurred, the concentration of apolipoprotein A-I increased by 12%. The drug was well tolerated by the patients, there were no undesirable effects calling for discontinuation of treatment. The results are discussed along with those of other authors who had the opportunity to administer the drug for a prolonged period. The authors mention also briefly the results obtained during treatment of patients with hyperlipoproteinaemias, using other hypolipidaemic drugs. PMID- 2331713 TI - [Relation of the occurrence of chromosome aberrations in human peripheral lymphocytes to the cell cycle]. AB - Experimental results confirmed that the best period of cultivation of human peripheral lymphocytes for chromosomal analyses in subjects exposed to mutagens and carcinogens is 44-48 hours when the dividing lymphocytes are in the first cellular cycle. With prolongation of the cultivation period of lymphocytes the values of chromosomal aberrations decline because in subsequent cellular cycles their number declines as a result of mitotic deaths of cells which contain unstable types of aberrations. PMID- 2331714 TI - [Smoking cessation using nicotine chewing gum in smokers with chronic diseases]. AB - Hundred smokers were admitted for treatment of smokers by means of nicotine chewing gum; they were divided into three groups: smokers without diseases associated with smoking, smokers suffering from bronchitis and smokers suffering from cardiovascular disease. In 1989 the results obtained in 94 patients were evaluated 12 months after the onset of treatment. Four smokers were eliminated. The value of nicotine dependence according to Fagerstrom was on average 7.6 +/- 1.8 points which is a strong dependence. The majority of smokers smoked 15 to 24 cigarettes per day, one third 25 cigarettes or more per day. Five-months treatment was completed by 70 subjects and after one year, abstinence was recorded in 46, i. e. 48% of those evaluated. Abstinence was verified by the absence of carbon monoxide in the expired air: 3.1 +/- 1.6 ppm CO. In individual groups abstinence was achieved in 42, 42 and 63% resp. No serious side effects of treatment nor abstinence symptoms were detected. They occurred only during the first months of treatment. In the treatment psychological support was emphasized, frequent contact of the patient and therapist and correct chewing of adequate amounts of chewing gum. Treatment of smokers with cardiovascular disease was without complications and without manifestations on the ECG tracing. Patients with chronic bronchitis had after one year's abstinence better FEV1 values in 25%. PMID- 2331715 TI - [Revival of thinking about euthanasia]. PMID- 2331716 TI - [The relation between economics and medicine in the implementation of a nationwide cardiovascular program]. AB - The health services, being part of the tertiary sphere, must rely as far as material resources are concerned on the results of the economic policy of the state. This has, however, also a feedback effect: economics can have favourable results only when the health status of the population permits the implementation of pretentious economic targets. Thus dialectic relations are involved. Nationwide health programmes must among others promote the health status of the population. It is, however, not possible for the health services to ensure these programmes self-handed. Every section of the population must be responsible for its share. This implies to legal, moral, economic professional, training and finally also political responsibility. The authors discuss the most important problems associated with ensuring mutual relations of these section in the implementation of the cardiovascular programme. PMID- 2331717 TI - [Location of the bundle of Kent in patients with Ebstein's anomaly of the tricuspid valve]. AB - The prequisite of better therapeutic results in patients with Ebstein's anomaly of the tricuspid valve is more perfect diagnosis not only of the severity of the malformed valve but also of other associated defects incl. the anomalous accessory bundle of Kent which causes the development of dangerous tachydysrhythmias. The authors present their own experience with the localization of the bundle of Kent by mapping the endocardium of the atria in seven children before a cardiac operation. In all ventricular preexcitation type B with the bundle of Kent in the posterior lower portion of the atrial septum was found. In two non-operated patients who died with tachydysrhythmia which could not be controlled, the bundle of Kent was confirmed by histological examination, in three it was severed by operation, two patients are waiting to be operated. The authors recommend interruption of the bundle of Kent always concurrently with operation of the malformed tricuspid valve and other associated cardiac defects. PMID- 2331718 TI - [Precordial mapping of the R wave in the diagnosis of rejection after orthotopic heart transplantation]. AB - In 15 patients after orthotopic transplantation of the heart the authors made repeated examinations of electromaps of the R wave and endomyocardial biopsies (TMB) during a long-term, at least one-year, investigation. In the detection of rejection EMB plays a dominating role. In three patients the authors found at the time of rejection a significant reduction of the R waves on maps, which correlated closely with the bioptic findings. It was revealed that maps of R waves are a good indicator of rejection of the transplanted heart. The examination may prove helpful when checking treatment of rejection but does not lead so far to a restriction of the number of endomyocardial biopsies of the heart. PMID- 2331719 TI - [Replacement of the aortic valve in patients over 60 years of age]. AB - The authors evaluated a group of operated patients above 60 years of age where the main cardiosurgical operation was a aortic valve replacement. The early mortality in the group comprising 49 patients was 4.1%. (Of 33 patients where the replacement of the aortic valve was an isolated operation none of the patients died. From another 16 patients where also the mitral valve had to be replaced or IHD had to be resolved by revascularization of the heart muscle by aortocoronary bypasses, two patients died.) During a check-up examination one year after operation 92% of the checked patients where in functional group I or II according to NYHA classification (before operation all were in group III or IV). Prostheses of aortic valves do not only considerably prolong the life even in older patients but also improve its quality. Advanced age alone is no contraindication for operation and the surgical risk is not greater than in younger age groups. The authors recommend to implant in advanced age bioprostheses because of the markedly lower risk of serious haemorrhagic complications in the long-term postoperative course. PMID- 2331720 TI - [The effect of body constitution on work capacity evaluated by means of mechanical efficiency]. AB - The utilizable sources of energy of the human organism are relatively restricted where by interindividual differences are not substantial, while differences in physical performance are extreme. The capacity to transform chemical energy into mechanical work, sometimes described also as the work capacity of the organism is evaluated by means of mechanical efficiency--ME. In men with varying amounts of training (incl. untrained ones), differing significantly as to the percentage of body fat (3.8-17.2%), assessed by measurement of ten skinfolds, the authors assessed ME on a treadmill. The highest ME values were recorded in trained sportsmen (endurance runners--32.4%), lowest in untrained middle-aged men (16.9%). The authors found a close negative correlation of ME and maximal oxygen consumption per kg body weight and values of body fat percentage. With the increasing percentage of body fat the values of ME decline, the prerequisites for effective transformation of chemical energy of the organism into mechanical work are reduced and the work capacity of the organism declines. PMID- 2331721 TI - [Rehabilitation of patients with multiple sclerosis]. PMID- 2331722 TI - [Changes in sexual reactivity in young women in Czechoslovakia]. AB - In a group of 2425 gynaecological patients during their stay in the spa of Frantiskovy Lazne the authors examined by interviews the marital sex life of the patients. They divided them into sub-groups by decades of their birth year (1911 to 1970). In women born between 1961 and 1970 they recorded a marked rise in the number of women who experienced only rarely orgasm during coitus (26%). This change was explained by the action of stressing factors of the social environment. The authors express the view that changes in the orgastic capacity of women are rather than sexual appetence a sensitive and useful indicator of psychological influences. PMID- 2331723 TI - [Plasmapheresis--a therapeutic method for immunity-related infertility?]. AB - In a 30-year-old woman with primary idiopathic sterility the immunological cause of infertility was assessed (spermagglutination antibodies in serum and in the ovulation mucus of the uterine cervix). The patient was treated without success by condom therapy, general and local immunosuppression. Therefore treatment by means of membrane separation plasmapheresis was started during two preovulation periods. Serum spermagglutination antibodies class IgM declined from the original titre of 1:1024 to 1:16, immediately after homologous inseminations they rose, however, to the original titre and the patient did not become pregnant. PMID- 2331724 TI - [Normal thyroid gland volume and factors which affect it under physiologic conditions]. AB - The introduction of accurate methods for assessment of the volume of the thyroid gland in vivo into clinical practice is a new aspect of the problem of the normal size of the thyroid in healthy subjects. So far we have only vague ideas on its value in the Czechoslovak population. Standards from abroad cannot be adopted mechanically and a local investigation is necessary which will evaluate also the possible persistence of regional differences. The influence of body weight on the volume of the thyroid is accepted in general and this explains also sexual differences. There are no unequivocal views on the effect of age and the stage of the menstrual cycle on the volume of the thyroid gland; few reports on the influence of the season; there is no definite proof of the effect of smoking and alcohol consumption. Precise sonographic measurements did not prove a correlation between the volume of the thyroid gland and basic laboratory parameters (plasma thyroxine, triiodothyronine, thyroglobulin level, level of free fractions of thyroxine and triiodothyronine, globulin binding thyroxine and adenopituitary thyrotropic hormone). So far we do not know when and to what extent omission of these factors distorts diagnostic and therapeutic conclusions. PMID- 2331725 TI - [Does aluminum affect the effectiveness of human recombinant erythropoietin in the treatment of anemia in dialyzed patients?]. AB - In five female patients with chronic renal failure who had regular dialyzation treatment it was revealed that hyperaluminaemia reduces the effect of erythropoietin. In view of the high cost of this drug it is reasonable to maintain the aluminium value at the lowest levels. PMID- 2331726 TI - [Action program of the Czechoslovak Ministry of Health and Social Affairs]. PMID- 2331727 TI - [Prognosis for requirements for oral antidiabetic agents in Bohemia]. AB - The authors elaborated the prognosis of requirements of oral antidiabetics (PAD) in the CSR, based on the estimate of the number of diabetics, using the method of demographic projection and the estimate of the number of diabetics treated by this therapy. The respective numbers of diabetics are circulated for five-year age-groups, separately for men and women. The need of PAD is derived from the mean daily dose per diabetic patient treated with PAD, separately for biguanides and derivatives of sulphonyl urea. The prognosis respects the basic factors which influence the need of PAD, i.e. the development of the diabetic population, incl. the evolution of its structure, and the development of the attitude to PAD therapy. The application of various assumptions on the future development leads various to variants of the prognosis. Comparison with the actual development is important for evaluation of applied therapeutic methods and for planning purposes. The results of the prognosis indicate that in 1995 the need of PAD in the CSR will vary between 140 and 190% of the consumption in 1980, however, as a result of an uneven development the annual increment could be as high as 19% or there could be a slight drop. PMID- 2331728 TI - [Risk factors for atherosclerosis in the early stages of diabetes]. AB - The author investigated in a long term study of 8.7 +/- +/- 3.9 years risk factors of atherosclerosis (RFA) in 70 offspring of both parents suffering from non-insulin-dependent diabetes. Their mean age at the onset of the investigation was 35.2 +/- 7.4 years. The author assessed the incidence of obesity, hypertension, hyperglycaemia and hyperinsulinaemia after oGTT, elevated levels of cholesterol, triglycerides, fibrinogen and a reduced ratio of HDL on electrophoresis. As risk factors they considered: Broca's index above 110%, blood pressure above 150/90 mm Hg and other values above the average + 2SD recorded in a control group of 33 healthy non-obese subjects without a diabetic family history; HDL values lower than the mean--2SD of controls. During the investigation period the incidence of obesity increased significantly (P less than 0.01); of hypertension (P less than 0.01); hyperglycaemia (P less than 0.05); hyperinsulinaemia (P less than 0.001) and the incidence of a low HDL ratio (P less than 0.01). The mean RFA values were lowest in offspring with a normal oGTT, higher in liminal glucose tolerance and highest in impaired glucose tolerance and diabetes. The most important RFA include an elevated fibrinogen level. The results indicate that in subjects with a high genetic risk of the development of non-insulin dependent diabetes already in the earliest stage conditions for the development of atherosclerosis are present. PMID- 2331729 TI - [Electromyographic findings in diabetics]. AB - In 1987-1988 239 patients with diabetes type I and II were subjected to electromyographic examinations. The sensory and motor neurograms (n. suralis, n. medianus, n. peroneus, n. tibialis) were evaluated as well as myograms (from the m. opponens pollicis, m. tibialis, anterior, m. soleus). In all patients a priori other possible neurotoxic influences were ruled out; the age of the patients did not exceed 60 years. Abnormal parameters of the evaluated neurograms and myograms were found also in all diabetics type II with a normal neurological finding. In type I diabetics this so-called electrophysiological neuropathy was found in the same group in 84.2% of the patients. The most sensitive nerve in diabetes in the authors' investigation was the n. suralis, the second most frequently abnormal finding was the motor neurogram of the n. peroneus. The authors did not find it possible to elaborate a scale of clinical-electromyographic correlation. PMID- 2331730 TI - [Biochemical findings in osteoporosis. II. The importance of zinc]. AB - The authors examined 33 cases of senile, 18 cases of postmenopausal and 9 cases of medicamentous osteoporosis and assessed serum and red cell zinc content. The mean blood levels of zinc were highest in the group of medicamentous osteoporosis. In all three groups the zinc level was reduced more frequently in serum than in red cells. PMID- 2331731 TI - [Altruism--unselfish help given by one person to another]. AB - Altruistic behaviour belongs to so-called prosocial activities. It is focused on the benefit of another human being who is in want or is threatened. Its substantial features include voluntariness, unselfishness and specific motivation, based on human mutuality and unity. Altruism was at the very beginnings of organized health care. As a result of the development of medicine the human attitude of the doctor to the patient, and thus also psychological care and treatment were pushed into the background. At present "patient-orientated medicine" is enforced which comprises a psychological approach with altruistic elements. PMID- 2331732 TI - [The epidemiologic situation regarding tuberculosis and the effectiveness of tuberculosis surveillance in Bohemia in 1988]. AB - In the CSR (10 million inhabitants) in 1988 the system of TB surveillance was completed which comprises the national TB programme, the central TB register and the evaluation TB unit. The incidence of respiratory TB in 1988 in the CSR was 15.5/100,000 population. In 71% of the patients the disease was confirmed by bacteriological examination (11.0/100,000 population). The incidence of extrapulmonary TB was 4.2/100,000 population. As compared with previous years, the number of patients declined except patients with already microscopically confirmed acid resistant rods in the sputum; their incidence, 5.5/100,000, remained the same in the CSR since 1986. In this incidence participated in particular middle-aged men. The prevalence of active TB of the respiratory system was 20.0/100,000 population. It was only 1.3 times higher than the incidence, because treatment of TB patients was successful and principles of dispensarization were respected. The number of deaths from TB was 98 (0.9/100,000). In 84 the diagnosis was established only during autopsy. The lethality was high in old people. The course of treatment was evaluated after one year in 1330 patients with respiratory TB diagnosed in 1987. Satisfactory therapeutic results were achieved in 98% of the patients. In the remaining (17) patients bacteriological negativization of the sputum did not occur due to complications of treatment or lack of patient cooperation. 70% of the patients had a therapeutic regime with rifampicin. In-patient treatment was emphasized; the total mean period of administration of antituberculotics was 9.3 months. PMID- 2331733 TI - [Current incidence and treatment of bronchogenic carcinoma in Czechoslovakia]. AB - Bronchogenic carcinoma is the most frequent cause of death for malignant tumours. The incidence of the disease is rising steadily. Treatment is effective only in the initial stages of tumour development. So far the most radical treatment is operation. Combination with other therapeutic methods (radiotherapy, chemotherapy) is useful. Unfortunately only a small percentage of lung tumours is detected in the readily treated initial stage. The operability varies between 6 and 9% of newly registered cases. The way to improvement of the position is active detection of tumours in risk groups of the population, more rapid diagnosis and therapy of tumours which sometimes grow extremely rapidly, and a combination of surgical, ionization a chemical therapy. PMID- 2331734 TI - [Does exogenous airflow resistance reduce endogenous airway resistance in healthy persons?]. AB - The aim of our investigation was to assess whether a preinserted model resistance of a certain magnitude will expand the airways during inspiration and thus reduce the resistance of the airways conceived as the sum of the value of the endogenous airway resistance without obstruction and the value of the exogenous pre-inserted model resistance. The model resistance and resistance of the airways were assessed by means of a whole-body plethysmograph. The airway resistance was evaluated in 10 healthy men during inspiration and expiration, using a dictated breathing pattern. When a model resistance of 0.75 kPa.l-1.s-1 was preinserted during dictated minute ventilation of 30 l.min-1 and an air current of 1 l.s-1 the value of the airway resistance increased markedly, as compared with the same breathing pattern without obstruction. The resistance increment was, however, by 30% lower than the expected value. At the same time the functional residual lung capacity increased. PMID- 2331735 TI - [Adjuvant therapy of lung cancer]. AB - The authors evaluated in a retrospective investigation the effectiveness of adjuvant postoperative chemotherapy (ChT) and radiotherapy (RT), as compared with surgery alone, according to morphological types and stages of cancer lung (CaP). In a group of 321 patients 143 were treated by operation alone, 36 by operation and RT and 53 by operation and ChT. ChT involved administration of Cyclophosphamide, 30 mg/kg, at three-week intervals, some of the patients were also given vincaalkaloids. Therapy was repeated after 6-month intervals. According to the gross mortality data the probability of survival (PP) was compared by Kaplan-Meier's method. Improved PP was proved in patients with small cell lung cancer (MbCa) treated by operation and ChT and in third-stage disease treated by adjuvant ChT. In stage I of CaP adjuvant ChT and RT cause deterioration of the perspective of survival, as compared with operation alone and in stage II adjuvant ChT and RT are no advantage. The authors recommend adjuvant ChT in patients with surgically treated small-cell carcinoma and in stage III of operated CaP. They draw attention to the different response of tumours to adjuvant ChT and RT according to types and stages of CaP, to the fact that RT does not prolong the survival and to the possibility of preoperative ChT and RT in some types and stages of CaP. PMID- 2331736 TI - [Congenital cystic dilatation of the intrahepatic bile ducts (Caroli disease)]. AB - In two men and three women aged 64-89 years on necropsy a localized form of congenital cystic dilatation of the intrahepatic bile ducts (Caroli's disease) was found affecting the left and/or one of the segments of the right liver lobe. There was diffuse fibrosis with striking reduction of the left lobe where the dilated bile ducts were macroscopically apparent only in two subjects with concurrent occlusion of the extrahepatic bile ducts by stones and carcinoma of the head of the pancreas. Segmental dilatation of the bile ducts of the right lobe was not associated with structural changes of the hepatic tissue. On microscopic inspection the wide open or collapsed dilated bile ducts had a fibrohyaline wall of different thickness. In the smaller peripheral bile ducts there were diverticulous deformations of the lumen with persistent inflammation in the deep mucosal folds. No neuroendocrine cells or dysplastic changes were found in the mucosa and glands of the intrahepatic bile ducts. PMID- 2331737 TI - [Neuropathology of the amnesia syndrome in old age]. AB - In the 8-10th decade of life, people can be found who are not demented in the sense of WHO definition, but who are amnestic ("a memory problem only"). This defect is probably a result of the lesion of recent declarative memory. Immediate and remote memory are almost intact. Neuropathology of 17 such brains found numerous plaques and tangles in amygdalas and especially tangles in the IIth and IIIth strata of the entorhinal cortex and in subicula of hippocampi in 11 out of them. The number of plaques and tangles in frontal, parietal and temporal neocortex in these cases was not significant. In two other cases no significant o "alzheimer-like" changes were found, but there was numerical atrophy of neurons of CA 1 sector of hippocampi in their caudal half perhaps due to chronic ischaemic lesion in one of them. In the other one there was an infarction of the left isthmus collateralis and retrosplenic cortex. In four cases no unequivocal structural basis for the amnesia was found--except slight numerical atrophy of large neurons of the nucleus basalis Meynerti. No significant diencephalic pathology was found. Severe "binswanger-like" changes were found in two cases of amnesia and in one case of control group, all of them were hypertonics. There exists a possibility that a part of "isolated" and relatively "benign" amnestic defects in old people is not a result of the aging of the brain but a sign of evolution of Alzheimer's disease and/or ischaemic vascular lesion of the brain destroying or disconnecting some of its information bottlenecks. PMID- 2331738 TI - [Hypersomnia with sleep apnea. I]. AB - The author gives an account of present knowledge on the syndrome of hypersomnia with sleep apnea (HSA). After a historical introduction he deals with the incidence of this syndrome in Czechoslovakia; there are few accounts of this syndrome in the Czech literature. The author holds the view that this affection which is very frequent in other countries frequently escapes diagnosis in this country because the patients are not examined by sleep polygraphy which is essential for the diagnosis of HSA. The author describes also individual symptoms of the affection, i.e. hypersomnia, impaired respiration during sleep with frequent apnoic intervals, obesity, cardiovascular disorders and psychic changes. He emphasizes also the frequent incidence of tissue hyperplasia in the oropharyngeal area which leads to stenosis in this area. PMID- 2331739 TI - [Hypersomnia with sleep apnea. II]. AB - In the submitted paper the author gives an account of different affection associated with the syndrome of hypersomnia with sleep apnea. They include diseases and malformations with stenosis of the upper airways in the oropharyngeal area, particularly marked during sleep. They comprise also affections of nervous structures which innervate muscles in this area. The author pays attention to the frequent incidence of this syndrome in children with hypertrophic tonsils and adenoid vegetations. In this connection he mentions the cot death syndrome where very often death occurs during the apnoic interval as a result of immaturity of nervous structures which regulate respiration during sleep. The author describes also pathophysiological mechanisms of development of HSA and the diagnosis of this affection where examination by sleep polygraphy is essential. In the subsequent part of the work the author reviews contemporary conservative and surgical treatment of HSA. PMID- 2331740 TI - [Prophylactic treatment of vasospasm with nimodipine in subarachnoid hemorrhage]. AB - Nimodipine, a calcium antagonist, was administered to 33 patients with subarachnoidal haemorrhage as prophylaxis of late ischaemic neurological deficiency. Despite the relatively high frequency of vasospasm during repeated angiographic examinations (27%), the general therapeutic effect in the group of treated patients was favourable. 52% patients improved and had no or only a minimal neurological deficit. Possible mechanisms of the favourable effect of nimodipine in subarachnoidal haemorrhage are mentioned in the discussion. PMID- 2331741 TI - [Phalloplethysmographic findings in aggressive sexual offenders]. AB - Using the phalloplethysmographic test, comprising 25 coloured slides of five categories, the author examined 100 sexual delinquents, who committed crimes involving sexual aggression of adult females. The same test was used in 100 men of a control group who had no disorders nor difficulties in sexual life. During exposure of the basic set of stimuli (adult and child heterosexual objects) men of the control group had a better ability to differentiate sex and age of sexual objects, they reacted more frequently and more markedly in a positive way to heterosexual adult subjects than men in the group of sexual aggressors. The latter, on the other hand, reacted more frequently in a positive way also to adult and child homosexual subjects. As regards age differentiation in heterosexual objects, the difference between the two groups was not significant. During exposure of slides with a sadistic theme positive reactions were significantly more frequently recorded in the group of sexual aggressors and only in men of this group positive reactions classified as large were recorded. Repeatedly positive reactions of average size were recorded in 26 sexual aggressors. PMID- 2331742 TI - [Determination of the oxidation phenotype in the Czechoslovak population using metoprolol]. AB - The authors assessed the oxidative phenotype type debrisochin/spartein in 97 healthy volunteers aged 23 to 56 years (45 men and 52 women). After metoprolol administration which served as a model substance, in doses of 100 mg p. o. at night, the authors collected urine during 8 hours. In the urine specimens they assessed by gas chromatography with detection of the electron capture (fig. 1) the metabolic ratio of metoprolol/alpha-hydroxymetoprolol (M/HM). The distribution of logM/HM on the frequency histogram was bimodal and made it possible to divide the group into extensive and poor metabolizers (fig. 2). The authors detected 6 poor metabolizers which corresponds to the results in the white population. The authors discuss the clinical impact of oxidative polymorphism in the treatment with metoprolol, diltiazem, quinidine and other drugs. PMID- 2331743 TI - [Use of an artificial heart and ventricular support system before heart transplantation]. AB - Acute, uncontrollable heart failure in young candidates for transplantation should be considered an indication for implantation of an artificial heart or artificial support of the hear ventricle, if a suitable graft for transplantation is not available at the time. It may be assumed that the two systems will ensure an adequate circulation and will improve organ function. The success of two-stage transplantation is cca 50%. Postoperative haemorrhage and infection are a major problem. Infection after implantation of an artificial heart is frequently incurable and is a clear contra-indication for further implantation. Thromboembolism caused by the artificial blood pump does not seem to be a serious complication when used temporarily. As none of the patients died due to failure of the pump and as also the other problems associated with the use of an artificial heart or a supporting device were successfully resolved, research and development of artificial blood pumps should proceed. Clinical results also confirmed the success of two-stage transplantation of the heart. PMID- 2331744 TI - [The role of digital subtraction angiography in the diagnosis of pulmonary anomalies]. AB - The authors evaluate the importance of pulmonary digital subtraction angiography (DSA) in anomalies of pulmonary tissue, the bronchial tree and vascular pulmonary malformations. In a group of eight patients, comprising unilateral pulmonary hypoplasia, pulmonary cysts, vascular malformations and pulmonary sequestrations, they analyze the asset of DSA and the place of this method in the diagnostic algorithm. Reduction of the invasive and risky character of the examination, lower costs, the possibility of immediate evaluation and subsequent processing of the picture and modification of the length of the record is one of the main advantages, as compared with classical angiography. PMID- 2331745 TI - [Long-term fate of intraventricular thrombi after myocardial infarct]. AB - Using two-dimensional echocardiography, the authors followed up 30 patients where in the course of treatment of acute myocardial infarction an intraventricular thrombus developed. A benign character (i. e. adjacent and immobile thrombus) was found in 21 patients, while a malignant (freely movable, floating, protruding) thrombus was recorded in 9 cases (70% as compared with 30%). All patients were followed up to the period of disappearance (regression) of the thrombus or within two years after infarction. The authors evaluated above all the ability of regression of thrombi and influencing their complication (above all systemic embolisms). In the whole group regression of thrombosis occurred in 25 patients (82%). In benign thrombi early regression--within three weeks after the development of infarction--occurred in 10 patients (33%) and late regression (more than three weeks) also in 10 patients. Analysis of the applied treatment revealed that all patients with early and nine patients with late regression of cardiac thrombosis had anticoagulation therapy till the thrombus disappeared. As to malignant thrombi, regression occurred only in five patients, always after at least three weeks. Systemic embolization (once into the cerebral arteries, twice into the arteries of the lower extremities) was recorded in three patients always with a malignant thrombus which was not affected by anticoagulant therapy. From the results of the investigation thus ensues that anticoagulation treatment during acute myocardial infarction and after it has in case of an intraventricular thrombus a favourable effect on the regression of the formed thrombus and it can reduce significantly the frequency of systemic embolisms which are the most serious complication. PMID- 2331746 TI - [Cardiovascular manifestations of systemic lupus erythematosus]. AB - The authors assessed the damage of the cardiovascular apparatus in a group of 57 patients with systemic lupus erythematosus. Arterial hypertension was recorded in 19 patients (33%). The other most frequent defects were damage of the pericardium in 12 patients (21%) incl. 8 (14%) who had a pericardial exudate. Ischaemic heart disease was recorded in six patients. Serious forms of vasculitis were recorded in three patients and haemodynamically significant aortal insufficiency in two patients. Other forms of cardiovascular damage were rare. PMID- 2331747 TI - [Improvement in the detection and control of hypertension in the industrial population of the Skoda Plzen factory 1976-1986]. AB - The authors investigated the effect of the ten-year intervention programme on the standard of detection, control and effectiveness of treatment of arterial hypertension in an industrial population. The prevalence of hypertension did not change during the investigation period (about 24%). In group B (1986) a decline of the blood pressure was recorded in all age groups on average by 10/0 mmHg (1.3/0 kPa) in men and by 15/9 mmHg (2/1.2 kPa) in women. In men detection improved and the ratio of treated hypertonics increased (p less than 0.05); in women the trend of improvement was not significant. The number of untreated subjects with hypertension did not change in the course of 10 years (15-16% of all hypertensive subjects). 50% hypertensive men and women were treated effectively in group A and 59% men with high blood pressure in group B; the ratio of effectively treated hypertonic women in group B did not change. There was no difference in the level of control of hypertension between men and women in either group. The differences in the prevalence and treatment of severe hypertonics (i.e. DPB greater than or equal to 110 mm Hg = 14.7 kPa) were not significant when comparing groups A and B (2.4% of group A and 4.1% of group B). PMID- 2331748 TI - HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. AB - Productive infection of human T lymphocytes by HIV-1 is dependent upon proliferation of the infected cell. Nonproliferating quiescent T cells can be infected by HIV-1 and harbor the virus in an inactive state until subsequent mitogenic stimulation. We use a modification of the polymerase chain reaction method, which is both sensitive and quantitative, to demonstrate that HIV-1 DNA synthesis is initiated in infected quiescent T cells at levels comparable with those of activated T cells. However, unlike that of activated T cells, the viral genome is not completely reverse transcribed in quiescent cells. Although this viral DNA structure can persist in quiescent cells as a latent form, it is labile. We discuss the lability of this HIV-1 DNA structure in relation to a "self-restricting persistent infection" by HIV-1 and propose that this may explain the low percentage of infected cells in the circulation of AIDS patients. PMID- 2331749 TI - Concentration of membrane antigens by forward transport and trapping in neuronal growth cones. AB - Formation of the nervous system requires that neuronal growth cones follow specific paths and then stop at recognition signals, sensed at the growth cone's leading edge. We used antibody-coated gold particles viewed by video-enhanced differential interference contrast microscopy to observe the distribution and movement of two cell surface molecules, N-CAM and the 2A1 antigen, on growth cones of cultured cortical neurons. Gold particles are occasionally transported forward at 1-2 microns/s to the leading edge where they are trapped but continue to move. Concentration at the edge persists after cytochalasin D treatment or ATP depletion, but active movements to and along edges cease. We also observed a novel outward movement of small cytoplasmic aggregates at 1.8 microns/s in filopodia. We suggest that active forward transport and trapping involve reversible attachment of antigens to and transport along cytoskeletal elements localized to edges of growth cones. PMID- 2331750 TI - DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. AB - The full-length cDNA for a transcriptional activator, DBP, that binds to the D site of the albumin promoter has been cloned. DBP belongs to a family of related transcription factors including Fos, Jun, CREB, and C/EBP, which share a conserved basic domain. However, unlike most other members of this family, DBP does not contain a "leucine zipper" structure. Among several rat tissues tested, significant levels of its protein are only observed in liver; yet, with the exception of testis, DBP mRNA is present in all of the examined tissues. DBP as well as its mRNA accumulate to significant levels only in adult animals. During chemically induced liver regeneration, DBP expression is rapidly down-regulated, suggesting that DBP may be involved in the proliferation control of hepatocytes. This cell growth-dependent expression of DBP, in contrast to its tissue specificity, appears to be controlled at the level of mRNA accumulation. PMID- 2331751 TI - A finger protein structurally similar to TFIIIA that binds exclusively to 5S RNA in Xenopus. AB - A 5S RNA binding protein (p43) in Xenopus is a major constituent of oocytes and comprises part of a 42S ribonucleoprotein storage particle. We have cloned and sequenced p43 cDNA from X. laevis and X. borealis as well as the cDNA for X. borealis TFIIIA. Like TFIIIA, p43 has nine zinc fingers, seven of which are exactly the same size as their counterparts in TFIIIA. Amino acid homology between the two proteins is restricted mainly to conserved residues characteristic of zinc fingers. In contrast to TFIIIA, which binds specifically to both 5S RNA and 5S RNA genes, p43 binds exclusively to 5S RNA. PMID- 2331753 TI - [Health promotion development as the basis for an effective health policy]. AB - Health promotion and development are an essential part of modern and effective health care. It is based on the awareness of social health priority, it tries to develop and apply adequate methods, it is the motive for the promotion of nation wide activities which foster health. It promotes individual efforts to improve health and contributes to the concretization and implementation of a health policy, the aim of which is to resolve basic health problems of society as a whole. PMID- 2331752 TI - Gradients of Kruppel and knirps gene products direct pair-rule gene stripe patterning in the posterior region of the Drosophila embryo. AB - Abdominal segmentation of the Drosophila embryo requires the activities of the gap genes Kruppel (Kr), knirps (kni), and tailless (tll). They control the expression of the pair-rule gene hairy (h) by activating or repressing independent cis-acting units that generate individual stripes. Kr activates stripe 5 and represses stripe 6, kni activates stripe 6 and represses stripe 7, and tll activates stripe 7. Kr and kni proteins bind strongly to h control units that generate stripes in areas of low concentration of the respective gap gene products and weakly to those that generate stripes in areas of high gap gene expression. These results indicate that Kr and kni proteins form overlapping concentration gradients that generate the periodic pair-rule expression pattern. PMID- 2331754 TI - [Mortality and mean life span as an indicator of population health status]. AB - The main source of data for the evaluation of the health status of the population are mortality statistics. The paper contains data on the standardized mortality and mean life span from the Annual World Health Report. The graphic presentation of data makes it possible to compare 15 selected European countries. In addition to the general mortality the cardiovascular mortality and the mortality from neoplasm is given. In the conclusion the author points out that the adverse health status of the Czechoslovak population must be improved not only by ensuring healthy living conditions but also by creating prerequisites for a change of the present lifestyle. PMID- 2331755 TI - [Testing student knowledge of emergency care at the Charles University School of General Medicine and the processing of certain conditions in primary emergency care into computerized educational training models]. AB - The objective expression of the state of knowledge of 6th year students of the Faculty of General Medicine in the field of emergency care is an important factor in the evaluation of their preparation for the medical profession, regardless of the specialty they choose. Knowledge of these data is essential for improvement of undergraduate teaching of emergency care. Suitable application of computer technique can supplement the possibilities how to achieve this. The application of so-called model situations on personal computers makes it possible to extend training of decision taking to all spheres of medical training. PMID- 2331756 TI - [Social pediatrics and ecology]. AB - The paper discusses the relations between social paediatrics and ecology. They must be used as a basis, because some social paediatric problems have oecological causes and their omission could lead to an erroneous interpretation of these problems. The authors draws attention to some of the most important oecological factors which may play a role in social paediatric practice. PMID- 2331757 TI - [Fulfillment of personnel staffing requirements in health facilities in Bohemia and individual regions as of September 30 1988]. AB - In the CSR an investigation was made to test the implementation of personnel norms in health institutions to the date of September 30, 1988. It was revealed that the norms were not implemented: there was a shortage of 12,106.38 medical posts, i.e. 27.7%, 1,425.88 working posts of pharmacists, i.e. 29.0%; as regards other university graduates, 3,422.51 posts were vacant, i.e. 55.5%, and as regards nursing staff there were 53,161.34 vacant working posts. There was a shortage of a total of 70,116.11 specialized health workers, the norm was met by 68.1%. This is the overall position but there are differences in particular groups and interregional differences too. The authors analyze in detail the position in the CSR by categories of workers and by regions in different health institutions. PMID- 2331758 TI - [Health care planning strategies and the need for demographic and operational research]. AB - Planning of health care is an indispensible prerequisite of social and economic development of every state. The European version of the WHO programme Health for All is suitable planning model. The programme is systematically conceived, it states general fundamental priorities and the sequence of the implementation of tasks to attain precisely defined goals. Its implementation calls for epidemiological, sociological and operational research in order to study the health status of the population, risk and protective factors and the function of the system of health services. A uniform overall national programme of health care should be elaborated and our nation-wide health programmes should form an integral part in it. PMID- 2331759 TI - [Motivation for medical studies]. AB - The authors submit results of three years' research which provided data on motivations leading to interest in medical studies among students. The results obtained by questionnaires from 304 respondents mention in the first place from a total of 30 identified elements interest in human biology, the functional influence of the family and emotional aspects. Confrontation of motivation with the achieved classification results during examinations revealed that the best mean marks are achieved by students motivated to medical studies by humanity, efforts to acquire more knowledge and active work in the Red Cross while still at primary and secondary school. In the respect women predominate. Less favourable average marks were recorded in those motivated by subjective motives and undefined interest. The assembled findings can be used in the process of education and training by aimed differentiation of the teaching process. PMID- 2331760 TI - [The role of the family physician]. AB - The general practitioner is the best person to take care of medical care of adults in the family, while the paediatrician looks after the children. The author speaks about the main aspects of family practice, the help of family members when coping with sickness of one of the members, the domiciliary care of patients, primary basic prevention in the family, help with family problems, advice and support of the family in relation to the social and aecological environment, assistance in case of death, losses and grief. Finally the author pays attention to talks with the family in general practice incl. their indications. PMID- 2331761 TI - [Socio-medical aspects of stress and adaptation]. AB - Based on a recapitulation of contemporary knowledge on stress and adaptations, the author investigates and analyzes sociomedical aspects of this problem. He draws conclusions on the necessity of some new theoretical views on the relationship of social and biological processes, laws and new approaches to the actual implementation of this relationship in conjunction with health protection and promotion of people in contemporary society. PMID- 2331762 TI - [The effectiveness of special schools in the comprehensive care of mentally retarded children]. AB - The allocation of children to auxiliary schools causes difficulties. With regard to the degree of mental retardation the children are usually placed in social care institutions. It was found that children attending day classes in social care institutions have more self-handed habits and skills than pupils of auxiliary schools. The author recommends the integration of auxiliary schools and day classes of social care institutions to achieve more expedient training of mentally retarded children, with the possibility of more intensive rehabilitation care. PMID- 2331763 TI - Effect of duration of ventricular fibrillation on defibrillation efficacy in humans. AB - The currently available automatic implantable cardioverter-defibrillator has proven highly successful for termination of ventricular tachycardia and fibrillation. Newer devices, however, permit lower energy shocks to be delivered initially and longer episodes of arrhythmia to occur before shocks are delivered. These changes may result in longer durations of arrhythmia before successful termination. Little is known about the effects of the duration of ventricular fibrillation on the efficacy of defibrillating shocks. In this study, we examined the efficacy of defibrillating shocks in 22 patients undergoing automatic implantable cardioverter-defibrillator implantation or generator change. Defibrillating shocks ranging from 300 to 600 V (5.9-24.2 J) were delivered in matched pairs after 5 and 15 seconds of ventricular fibrillation. For the 300-V shocks (5.9 J), defibrillation was accomplished in 82% of patients when the shocks were given after 5 seconds of ventricular fibrillation and in only 45% of patients when the shocks were delivered after 15 seconds (p less than 0.01). At higher energies, there was no difference in the efficacy of defibrillation shocks delivered after 5 compared with 15 seconds of ventricular fibrillation. The postshock aortic, systolic, and diastolic blood pressures were significantly lower when the shocks were given after 15 seconds of ventricular fibrillation than after only 5 seconds. We conclude that the duration of ventricular fibrillation affects defibrillation efficacy especially at energies that are relatively low compared with maximal device outputs and that longer episodes of ventricular fibrillation cause more postshock hemodynamic depression. These observations have implications for defibrillation threshold testing at the time of device implantation and for the design and programming of future automatic implantable antitachycardia devices. PMID- 2331764 TI - Resetting of ventricular tachycardia by single extrastimuli. Relation to slow conduction within the reentrant circuit. AB - Although both transient entrainment and resetting with single extrastimuli have been demonstrated during sustained ventricular tachycardia related to previous myocardial infarction, the relation between these phenomena has not been defined. Because transient entrainment is only demonstrated when the mechanism of a tachycardia is reentry with an excitable gap, the resetting response to timed premature extrastimuli was studied in patients with ventricular tachycardia and correlated with the ability to demonstrate transient entrainment. The importance of the location of pacing and recording electrodes relative to regions of slow conduction within the reentry circuit for demonstrating specific characteristics of the resetting response after single extrastimuli was examined in 16 patients with 21 distinct morphologies of ventricular tachycardia related to coronary artery disease. At electrophysiological study, intracardiac electrograms were recorded simultaneously from four sites in the right ventricle and four sites in the left ventricle during ventricular tachycardia. Both resetting and transient entrainment could be demonstrated for 18 of the 21 (86%) ventricular tachycardias. The resetting response at each intracardiac recording site was defined as orthodromic or antidromic, based on the conduction time from the pacing stimulus to the recording site and the morphology of the captured (advanced) electrogram. An orthodromic resetting response was associated with demonstration of transient entrainment at 76 of 82 (93%) recording sites, implying that the pacing site was proximal and the recording site was distal to a region of slow conduction. In contrast, an antidromic resetting response was associated with transient entrainment at only six of 154 (4%) recording sites, suggesting that the pacing site was not separated from the recording site by a region of slow conduction (p = 0.001). The return cycle at the site of pacing exceeded the tachycardia cycle length in all episodes of ventricular tachycardia. At orthodromically activated recording sites, however, resetting was associated with a return cycle less than the tachycardia cycle length. Thus, orthodromic resetting demonstrates that a pause is not an integral part of the resetting response but that premature extrastimuli preexcite the reentrant circuit by entering the excitable gap, conducting through a region of slow conduction, and emerging distally without a change in activation sequence. In all episodes of ventricular tachycardia, the slope of the return cycle at the pacing site was determined by the conduction properties to the orthodromically activated sites, with increasing patterns (n = 6) produced by progressive conduction delay in the reentrant circuit at shorter coupling intervals and flat patterns (n = 3) produced by a constant orthodromic conduction interval.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2331765 TI - Outcome after a "perfect" Fontan operation. AB - A study was undertaken to determine the early and long-term outcomes dictated by the Fontan state per se (a state in which the force driving pulmonary blood flow is solely or largely a residue, in the systemic venous pressure, of the main ventricular chamber's contractile force) and the transition (by surgery) to it from the state of congenital heart disease under optimal conditions (after a "perfect" Fontan operation). The primary study design used a solution of a multivariate risk factor equation for death, by which survival rate under optimal conditions was predicted to be 92%, 89%, 88%, 86%, 81%, and 73% at 1 month, 6 months, and 1, 5, 10, and 15 years, respectively, after the Fontan operation. The hazard function (instantaneous risk of death at each moment in time after the operation) had an early rapidly declining phase of hazard that at about 6 months began to give way to a late hazard phase, which was rising by about 6 years after surgery. A secondary study design, using the theory of competing risks, yielded survival and hazard function information very similar to that of the primary study design. The functional capacity of the patients as expressed by New York Heart Association class was less, the longer the period of follow-up. No risk factors (other than older age at time of surgery) were found for the late decline in survival or the decline in functional status. The inference is that the premature decline in survival and functional status and the late rise in hazard function are from the Fontan state per se and that the Fontan operation is, therefore, palliative but not curative. PMID- 2331766 TI - Ventricular volume characteristics in double-inlet left ventricle before and after septation. AB - Septation is one of the surgical choices for double-inlet left ventricle, yet postoperative hemodynamics have not been well defined. We studied ventricular volume characteristics in 10 patients with double-inlet left ventricle before and after septation. Preoperative end-diastolic volume (EDV) of the ventricle was 291 +/- 111% (+/- SD) of normal and ejection fraction (EF) was 0.59 +/- 0.07. Postoperatively, EDV of the right-sided ventricle (RV) was 82 +/- 24%, and EDV of the left-sided ventricle (LV) was 153 +/- 41%. Ejection fraction of the RV was 0.77 +/- 0.10, and LVEF was 0.49 +/- 0.13. On the short-axis view of two dimensional echocardiography, fractional change of the cross-sectional area was 0.65 +/- 0.16 for the RV and 0.23 +/- 0.11 for the LV. Fractional shortening of the septum-to-ventricular free wall axis was 0.51 +/- 0.17 in the RV and -0.05 +/ 0.09 in the LV. Analysis of the curvature of the new septum during cardiac cycle on two-dimensional echocardiography revealed that the septum shifted to the right side during systole in all patients in whom the systolic LV/RV pressure ratio was larger than 1.0. The septum shifted toward the LV during diastole in eight patients in whom end-diastolic pressure in the RV was higher than or equal to that in the LV, whereas it remained in the right side in two patients with higher left-side pressure. The cardiac index of these two patients was 2.4 and 2.6 l/min/m2, respectively, whereas it averaged 4.4 +/- 1.0 l/min/m2 in the other eight patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331767 TI - Redistribution of regional and organ blood volume and effect on cardiac function in relation to upright exercise intensity in healthy human subjects. AB - To determine the effect of relative exercise intensity on organ blood volume and its relation to cardiac function, changes in relative blood volume and cardiac function were monitored with radionuclide techniques in 14 healthy volunteers. After labeling the subject's red cells with technetium 99m, we acquired data at rest, zero-load cycling, and at 50%, 75%, and 100% of maximal oxygen uptake. From rest to zero-load cycling, leg blood volume decreased 32 +/- 2% (mean +/- SEM), whereas relative end-diastolic blood volume increased 9.6 +/- 1.2%, and lung blood volume increased 18 +/- 2%, suggesting that the lungs may act as a blood volume buffer during periods of acutely increased venous return. With relative increasing exercise, leg blood volume stabilized, and then the blood volume in the abdominal organs decreased, further augmenting cardiopulmonary blood volume; leg blood volume and abdominal blood volume decreased by 23 +/- 2% and 19 +/- 2% from baseline, respectively, whereas thoracic blood volume increased 38 +/- 4%. In the abdomen, large decreases in blood volume were observed in the spleen (46 +/- 2%), kidney (24 +/- 4%), and liver (18 +/- 4%). In contrast, lung blood volume increased 50 +/- 4%, with the upper lung fields increasing more than the lower. Blood sampling revealed an increase in the hematocrit level by 4.3 +/- 0.4 units at peak exercise that paralleled the decrease in splenic blood volume (r2 = -0.64, p less than 0.001), suggesting a role for the spleen in augmenting cardiovascular performance by the release of concentrated red blood cells into general circulation. We conclude that upright exercise results in marked blood volume shifts from the legs and abdominal organs to the heart and lungs in a dynamic process correlating closely with oxygen consumption. PMID- 2331769 TI - Positron emission tomographic imaging of cardiac sympathetic innervation and function. AB - Sites of uptake, storage, and metabolism of [18F]fluorodopamine and excretion of [18F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [18F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [18F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function. PMID- 2331768 TI - Black-white differences in exercise blood pressure. The Lipid Research Clinics Program Prevalence Study. AB - After exclusion of persons on blood pressure medication or with prevalent cardiovascular disease, we studied 83 black and 2,548 white men and 113 black and 1,519 white women 20-69 years old from the Lipid Research Clinics population sample who had performed a standardized treadmill exercise test. Resting systolic and diastolic blood pressures were similar in black and white men, but the diastolic pressure was significantly higher in black than in white women (81.4 vs 77.4 mm Hg). Body weight was higher in black than in white women, and reported physical activity was higher in black than in white men. The proportion of smokers was somewhat higher in blacks than in whites. During the treadmill exercise test with a modified Bruce protocol, mean systolic blood pressure at stage 2 was 174 mm Hg in black men and 166 mm Hg in white men (p less than 0.02), but stage 2 blood pressures did not differ between black and white women (153 and 152 mm Hg, respectively). Even after adjustments were made for levels of baseline characteristics (age, weight, resting systolic blood pressure, smoking, low density lipoprotein cholesterol, physical activity, and alcohol intake), black men responded with a 7-mm Hg higher systolic blood pressure during exercise than white men (p less than 0.01). Another new finding was a highly significant positive association between stage 2 systolic blood pressure and low density lipoprotein cholesterol in men. The findings suggest a higher systemic vascular resistance during exercise in the selected sample of black men, which is consistent with the higher incidence of hypertension in black men. PMID- 2331770 TI - Thallium 201 kinetics in stunned myocardium characterized by severe postischemic systolic dysfunction. AB - The hypothesis tested in this study was that despite the presence of severe postischemic myocardial dysfunction ("stunning"), the extraction and subsequent intracellular washout of thallium 201 should be preserved as long as irreversible sarcolemmal membrane injury was avoided. To produce myocardial stunning, 19 open chested dogs with a critical left anterior descending coronary artery (LAD) stenosis underwent 10 5-minute periods of total LAD occlusion, each interspersed by 10 minutes of reperfusion by reflow through the critical stenosis. In another 12 control dogs observed for the same time period, no LAD occlusions were performed after placement of the critical stenosis. Hemodynamics, regional myocardial thickening by quantitative two-dimensional echocardiography, and microsphere-determined regional blood flows were serially measured. In 18 stunned dogs, systolic thickening in the LAD zone was markedly reduced to 0.4 +/- 2.4% at 40 minutes after the 10th reperfusion period compared with 32.5 +/- 2.2% thickening (p less than 0.001) in 12 control dogs at a matched time. The 201Tl first-pass extraction fraction determined by a double-isotope method using intracoronary 201Tl administration was comparable after the 10th reflow in a subgroup of 13 stunned (0.78) and six control (0.79) dogs. The T1/2 for the intracellular washout rate was also not significantly different in another group of six stunned (60 +/- 13 minutes) and six control (53 +/- 14 minutes) dogs, nor was the percentage of the 201Tl dose initially distributed in the interstitial compartment (11 +/- 3% vs. 7 +/- 2%). Systemic hemodynamics and regional flows were comparable in the two groups at 40 minutes after the 10th reflow. No dog had evidence of myocardial necrosis by triphenyl tetrazolium chloride staining. Thus, normal myocardial 201Tl extraction and washout kinetics are observed in a canine model of severe postischemic dysfunction (stunning) produced by repetitive brief LAD occlusions. These findings might have important clinical implications concerning the application of rest 201Tl scintigraphy for evaluation of perfusion and viability in patients with coronary artery disease and regional myocardial asynergy that is ultimately reversible. PMID- 2331771 TI - Double-wave reentry as a mechanism of acceleration of ventricular tachycardia. AB - By using a Langendorff-perfused ring of anisotropic rabbit epicardium, sustained reentrant ventricular tachycardia with a cycle length of 168 +/- 13 msec (n = 26) was induced by programmed electrical stimulation. Continuous left ventricular epicardial mapping with 256 simultaneously recorded unipolar electrograms demonstrated that the tachycardia was based on circuital movement of the impulse around a fixed obstacle. Because of the anisotropic properties of the myocardium, the circuit consisted of a ring with segments in which the circulating wave propagated slowly (20 +/- 2 cm/sec) or faster (62 +/- 4 cm/sec). This was related to transverse or longitudinal propagation in relation to fiber direction. In six of 26 experiments, sudden acceleration in rate of the tachycardia was observed during programmed electrical stimulation. This acceleration was caused by the occurrence of double-wave reentry (two successive waves traveling in the same direction and using the same circuit). In one of the experiments, induction of double-wave reentry was only possible at basal conditions but not after the administration of a class III antiarrhythmic drug. In a seventh experiment, induction of double-wave reentry became possible after the administration of a class IC antiarrhythmic drug. Because conduction velocity around the ring was depressed during acceleration, the total revolution time of the circuit during double-wave reentry was about 120% of that during single-wave reentry. Ventricular tachycardias in which double-wave reentry could be elicited had longer cycle lengths (197 +/- 11 vs. 156 +/- 8 msec, p less than 0.001) and larger excitable gaps (71 +/- 16 vs. 28 +/- 5 msec, p less than 0.001) than those not showing this phenomenon. Double-wave reentry might have important clinical implications in understanding ventricular tachycardia acceleration during programmed electrical stimulation, proarrhythmic effects of drugs, and pathophysiology of rapid ventricular tachycardias. PMID- 2331772 TI - Estrogen modulates responses of atherosclerotic coronary arteries. AB - Although evidence indicates that estrogen replacement therapy reduces risk of coronary heart disease, the mechanism remains unknown. Among the possibilities are that estrogen replacement therapy may 1) inhibit growth of atherosclerotic plaque and 2) decrease the prevalence of transient myocardial ischemia and myocardial infarction by modulating vasomotion in atherosclerotic coronary arteries. Using quantitative coronary angiography, we determined vasomotor responses of atherosclerotic coronary arteries in ovariectomized cynomolgus monkeys; six were given physiological estrogen "replacement" by subcutaneous implants, and six were not. Intracoronary infusion of the endothelium-dependent dilator acetylcholine (1 X 10(-6) M) caused paradoxical constriction of coronary arteries (from 1.2 +/- 0.2 to 0.6 +/- 0.1 mm, p less than 0.05) in the estrogen deficient monkeys. However, acetylcholine tended to minimally dilate the left circumflex coronary artery in estrogen-treated monkeys (from 1.2 +/- 0.2 to 1.5 +/- 0.2 mm, p greater than 0.2). Although estrogen replacement therapy reduced plaque extent in coronary arteries, altered vasomotion was not related to plaque extent. We conclude that estrogen modulates vasomotion of atherosclerotic coronary arteries of monkeys and speculate that estrogen-modulated constrictor responses of atherosclerotic coronary arteries may reduce the incidence of coronary heart disease in postmenopausal women. PMID- 2331773 TI - Physiological early diastolic intraventricular pressure gradient is lost during acute myocardial ischemia. AB - A consistent pattern of intraventricular regional pressure gradients exists under physiological conditions during the rapid filling phase of diastole in the normal dog left ventricle. We hypothesized that this pressure gradient pattern is caused, in part, by early diastolic recoil of the left ventricular walls in conjunction with release of elastic potential energy stored during systole, generating suction and thus contributing to diastolic filling. If so, any condition that interferes with normal regional systolic function might be expected to modify the pattern of the normal early diastolic intraventricular pressure gradients. Accordingly, the present study was designed to determine whether acutely induced regional systolic left ventricular mechanical dysfunction is accompanied by changes in the pattern of the early diastolic intraventricular pressure gradients. Acute myocardial ischemia was induced by balloon occlusion of the left anterior descending coronary artery (LAD) in nine anesthetized closed chest dogs. The maximum early diastolic intraventricular pressure gradient (MIVP) was measured between the mid-left ventricle and apex with a dual-sensor micromanometer (3-cm spacing between the sensors) before and 20 minutes after LAD occlusion. Ejection fraction (EF) and number of dyskinetic chords (DChords) were measured from left ventricular contrast ventriculograms. Twenty minutes after LAD occlusion, the nine dogs evidenced significant changes in EF (56 +/- 10% to 37 +/ 8%), DChords (0 +/- 0 to 17 +/- 16 chords), left ventricular minimum pressure ( 1.7 +/- 0.5 to 0.0 +/- 1.5 mm Hg), left ventricular end-diastolic pressure (4.2 +/- 1.2 to 5.9 +/- 2.2 mm Hg), and heart rate (90 +/- 17 to 103 +/- 18 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331774 TI - James B. Herrick lecture. The sad plight of the clinician-clinical investigator. "Don't boil the frog in the pot". PMID- 2331775 TI - Sex differences and coronary heart disease. A case of comparing apples and pears? PMID- 2331776 TI - Enzymatic infarct size and its significance for evaluation of thrombolytic therapy after acute myocardial infarction. PMID- 2331777 TI - Rearing cats with eyelid suture has both early and late effects on cells in the lateral geniculate nucleus. AB - We have assessed the effects of duration of infant-onset deprivation, and therefore the age of the subject at the time of data collection, on the physiology and morphology of cells in the lateral geniculate nucleus (LGN) of cats. Twenty-two kittens underwent lid suture. Electrophysiological experiments were performed in 12 of these subjects when they were between 5 and 16 months of age. The remaining 10 cats were studied between 17 and 29 months. In 16 of these same subjects we also measured LGN soma sizes to permit a direct within-subject comparison of the morphological and physiological effects of lid suture. Physiological data from cats recorded before 17 months of age showed a reduction in the encounter rate of Y-cells in deprived LGN laminae. In contrast, none of the cats which were 17 months or older at the time of recording showed a reduction in the encounter rate of deprived Y cells, giving the appearance of a more normal X/Y-cell ratio. Preliminary observations suggest that these late changes in the physiological effects of deprivation are not due to a recovery of Y-cells, but are more likely due to the superimposition of a reduction in the encounter rate for X-cells known to be typical of a variety of adult-onset deprivations. Finally, the physiological and morphological differences between non-deprived and deprived LGN laminae are correlated for the individual subjects. PMID- 2331778 TI - Sexual dimorphism in the parastrial nucleus of the rat preoptic area. AB - This work investigates the possible existence of sex differences in the volume of the parastrial nucleus (PSN), a component of the preoptic area in the rat. The effects of postnatal (on day 1 after birth) male orchidectomy and female androgenization on this nucleus were studied. The volume of the PSN was greater in the control females than in the control males and postnatal treatments reversed this sexual dimorphism. PMID- 2331779 TI - Comparative responsiveness of early chick neural tube neurons to muscle conditioned medium, laminin, NGF and fibronectin. AB - Dissociates from the metencephalic basal plate of early chick embryo neural tubes containing the trigeminal (V) motor nucleus were cultured on substrates conditioned with appropriate target-derived muscle conditioned medium (MCM), laminin (LAM), MCM with nerve growth factor (NGF) in the medium, and fibronectin (FN). Comparisons were made of neuronal survival, the number of neurons with processes, and the length of processes elaborated. It was found that both MCM and LAM significantly enhanced survival and neuritic production from this population when compared to controls grown on a collagen-polyornithine substrate, but MCM surpassed LAM in these measures. When the neurons were grown on an MCM conditioned substrate with an NGF-supplemented medium, no improvements were produced over the MCM or the NGF conditions alone. Therefore, the two do not appear to act in synergy, as NGF and LAM have been shown to do. FN produced no enhancement of any of the measures taken from this population. An ELISA analysis revealed no detectable LAM in the early target MCM. These results indicate that the specific responsiveness of this early neural tube population to its target MCM is not mediated by LAM, but the growth-enhancing component acts in a similar manner, although its influence is more potent. PMID- 2331780 TI - Developmental expression of protein kinase C isozymes in rat cerebellum. AB - Previously we showed that protein kinase C (PKC) isozymes (types I, II, and III) have distinctive neuronal localizations in cerebellum. In the present study, we followed the different appearances of these isozymes during the postnatal development of cerebellum. By immunoblot analysis, type I PKC was found to be low within 2 weeks after birth; an abrupt increase was observed between 2 and 3 weeks and leveled off afterwards. By immunofluorescent staining, the type I PKC specific antibody recognized the cell bodies and dendrites of Purkinje cells. The increase of this isozyme between 2 and 3 weeks of age correlates with the spreading of Purkinje cell arborization, at which time bulk of synaptogenesis between dendritic spines and axons of granule cells occurs. Both type II and III PKCs were present in granule cells. At birth, the level of type II PKC was relatively high compared to that of type III PKC, and the type II PKC-specific antibody stained the granule cell precursors in the external layer more heavily than did the type III PKC-specific antibody. The level of type II PKC declined slightly after birth and increased again at one week and plateaued after three weeks, whereas that of type III PKC increased gradually until leveling off after three weeks. Throughout the development, the type III PKC-specific antibody also stained the cell bodies of Purkinje cells but not their dendrites. These results demonstrate that the developmental expression of PKC isozymes is under separate control, and their distinct cellular and subcellular localizations suggest their unique functions in the cerebellum. PMID- 2331781 TI - The developmental expression of the cholinergic-specific antigen Chol-1 in the central and peripheral nervous system of the rat. AB - Antisera raised by the injection into sheep of presynaptic plasma membranes isolated from the purely cholinergic electromotor nerve terminals of Torpedo marmorata recognize a cholinergic-specific epitope, designated Chol-1 which has been shown to be gangliosidic in nature both in Torpedo (Richardson et al., 1982) and guinea-pig brain (Ferretti and Borroni, 1986). In rat brain the serum recognizes a group of antigenically-related minor gangliosides (Chol-1 alpha, beta and gamma) which migrate just below the standard gangliosides GQ, GT1B and between GD1b and GD1a, respectively. We have studied the developmental expression of these gangliosides in rat brain and hippocampus and in the neuromuscular junction of rat intercostal muscle in an attempt to correlate their expression with specific events in the development of the cholinergic neuron. The period in which Chol-1 is first detected suggests that it is expressed relatively late during the maturation process of the cholinergic synapse. This is supported by the finding: (a) that it is not detected in the growth cones (immature nerve terminals) in 5-day-old rat brain but is in the whole brain implying that only the more mature nerve terminals present at this stage express Chol-1; and (b) that Chol-1 is first expressed in the neuromuscular junction at a time in which functional synapses are already present. These results argue against a role for the Chol-1 antigens as recognition molecules in the formation of cholinergic synapses. The expression of Chol-1 in both the hippocampus and the neuromuscular junction correlates well with the establishment of the adult pattern of innervation; thus the Chol-1 antigens may be seen as markers for mature cholinergic terminals. PMID- 2331782 TI - Lectin staining of saccharides in the normal and hypothyroid developing organ of Corti. AB - Lectin staining has been used to detect mono- and oligosaccharides in normal and hypothyroid developing organs of Corti in the rat. Eight developmental stages were studied (1, 5, 8, 10, 15, 20, 50 and 60 days after birth). Congenital hypothyroidism was induced by oral administration of propylthyouracil to pregnant rats. Labelling of the tectorial membrane with 3 lectins, Ulex europaeus agglutinin-I (UEA-I), Lens culinaris agglutinin (LCA) and Ricinus communis agglutinin-I (RCA-I) showed no significant differences between normal and hypothyroid animals. Staining with peanut agglutinin (PNA) showed that the hypothyroid adult tectorial membrane (but not the normal one) possesses the disaccharide galactose + N-acetyl galactosamine. Phaseolus vulgaris agglutinin-L (PHA-L) labels the whole tectorial membrane in both groups of animals, but the staining is more intense in the hypothyroid one for a narrow band of oligosaccharide located just between the tectorial membrane and the underlying organ of Kolliker. Both soybean agglutinin (SBA) and succinylated wheat germ agglutinin (WGA) stain the tectorial membrane as well as the cytoplasm of the cells constituting the inner portion of the organ of Kolliker; this latter feature disappears in the normal animals about the 8th postnatal day, but it is abnormally preserved until the 60th postnatal day in the hypothyroid ones. In the adult hypothyroid animals, 3 of the lectins (LCA, PHA-L and WGA) stain extracellular conglomerates located under the synaptic pole of the outer hair cells. PMID- 2331783 TI - NCAM gene expression during the development of cerebellum and dentate gyrus in the mouse. AB - The neural cell adhesion molecule (NCAM) is thought to be involved in several important events during CNS vertebrate development. This study provides additional information concerning the biochemical determination and anatomical localization of NCAM transcripts. Using S1 nuclease protection assays (S1-NPAs), NCAM transcripts in brain appear highest at birth, with NCAM messenger levels reduced some 20-fold by adulthood. By use of in situ hybridization, NCAM mRNA is demonstrated to be developmentally regulated in the cerebellum and hippocampus. The in situ hybridization findings, in addition to providing results to compare with past studies of NCAM immunolocalization, reveal that NCAM expression in dentate gyrus granule cells and cerebellar Purkinje cells is correlated with the final stages of axonal growth, e.g., synaptic stabilization. In situ hybridization demonstrates a developmental outside-to-inside gradient of NCAM transcripts in the dentate gyrus. Neurological mutant mice, reeler and stagger, provide evidence that NCAM expression is normal in the brain regions investigated, and does not correlate with the developmental perturbations present in these strains. PMID- 2331784 TI - Induction of the vesicular monoamine transporter by elevated potassium concentration in cultures of rat sympathetic neurons. AB - The expression of the vesicular monoamine transporter was studied in newborn rat sympathetic neurons and compared to that of the catecholamine biosynthesis enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase. The vesicular monoamine transporter was assayed using the specific ligand [3H]dihydrotetrabenazine. In cultures grown for 10 days in the presence of 35 mM K+, tyrosine hydroxylase activity and the density of [3H]dihydrotetrabenazine binding sites were increased by a similar 2-3-fold factor, while dopamine-beta hydroxylase activity and protein level were unchanged. Under these conditions, choline acetyltransferase activity was depressed by 90%. The induction of the vesicular monoamine transporter by high K+ was dependent upon Ca2+ entry through slow calcium channels since it was inhibited by the diphenylbutylpiperidine antagonist fluspirilene and by 20 mM Mg2+, and was enhanced by the dihydropyridine agonist, Bay K8644. The induction of the vesicular monoamine transporter by neuronal depolarization indicates the existence of a Ca2(+) dependent mechanism of coregulation for this intrinsic component of monoaminergic synaptic vesicles and tyrosine hydroxylase. On the other hand, the apparent absence of dopamine-beta-hydroxylase induction is probably due to the continuous secretion of this intravesicular enzyme by the depolarized sympathetic neurons, an effect already observed in trans-synaptically stimulated adult sympathetic ganglion and adrenal medulla. PMID- 2331785 TI - Termination of the hormone-sensitive period for differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats. AB - The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat brain is several-fold larger in males than in females. The volume of the SDN-POA can be influenced significantly by the hormone milieu during early postnatal life. The purpose of the present study was to identify when termination of the sensitive period occurs during which exogenous androgen administration influences SDN-POA volume in males gonadectomized on the first day of postnatal life (fales) or intact females. Analysis of the SDN-POA in fales showed that testosterone propionate (TP, 500 micrograms) treatment on days 2, 3, 4, or 5, significantly increased its volume over values from oil-treated fales. In contrast, TP treatment in fales on days 6, 7, or 8, failed to increase SDN-POA volume. A similar pattern was observed in females treated with TP. Females treated with TP (500 micrograms) on days 2, 3, 4, or 5, showed a significant increase in SDN-POA volume compared to the values from oil-injected animals, while the same TP treatment in females on days 6, 7, or 8, resulted in no such enhancement. The absolute and relative change in SDN-POA volume following postnatal androgen treatment is greater in males than in females. We conclude that (1) SDN-POA development is sensitive to hormone action through postnatal day 5 and then abruptly becomes insensitive to this dosage of TP, and (2) although the temporal pattern of the response is similar in males and females, androgen exposure postnatally results in a consistently greater increase in the male SDN POA volume than in the female's. This greater response may be due to exposure prenatally to endogenous androgen in males. PMID- 2331786 TI - Transforming growth factor beta 1 is a potent survival factor for rat embryo motoneurons in culture. AB - We have studied the effects of transforming growth factor beta 1 (TGF beta 1) on the survival of embryonic motoneurons in culture. For this purpose, E14 rat embryo motoneurons were purified to more than 90% homogeneity by cell sorting and cultured at low density on monolayers of cortex astrocytes. Subnanomolar concentrations of TGF beta 1 (40-500 pM) increased the survival of motoneurons 2 fold after 9-11 days in culture. The increase in choline acetyltransferase (ChAT) activity per culture caused by TGF beta 1 was attributable to its effects on survival. Comparable results were found with motoneurons cultured on lysed astrocytes, suggesting that the effects of the factor are not mediated by non neuronal cells, but that motoneurons are a target for TGF beta 1. PMID- 2331787 TI - Afferent innervation patterns in crista ampullaris of the mouse during ontogenesis. AB - The development of vestibular afferent innervation patterns was studied by labeling the peripheral terminations between gestation day 17 and postnatal day 10. Extracellular injections of horseradish peroxidase were performed into vestibular ganglia in mouse otocysts maintained in vitro for several hours. At gestation days 17 and 18, the afferent innervation patterns were characterized by the presence of a few collaterals that arose from the parent fiber and sometimes ended by swellings or by enlargement extended by filopods rising to the epithelium surface. At the 20th gestation day the first endings differentiated into boutons or calyces were seen. At birth, the afferent innervation consisted of collaterals that could terminate either in boutons or in incomplete thin calyces. Starting on postnatal days 1 and 2, boutons and calyces became more pronounced and 3 afferent innervation patterns could be distinguished, i.e., calyx, dimorphic, and bouton. By postnatal day 5, the filopods had disappeared and the characteristic endings on type I or II cells were clearly individualized. On postnatal day 10, the afferent innervation patterns were comparable to those in the adult. These results are discussed in relation to ultrastructural data concerning the synaptogenesis and to the physiological development that have been described during the first postnatal days. PMID- 2331788 TI - Purkinje cell loss is due to a direct action of the weaver gene in Purkinje cells: evidence from chimeric mice. AB - Within the cerebellum of the adult homozygous weaver mutant mouse there is an approximate 50% reduction in the number of vermal Purkinje cells. It is not known if this deficit is due to a primary action of the weaver gene or if the cell loss is due to a secondary effect of the weaver gene. We examined this question using chimeric mice, produced by fusing C57BL/6 homozygous or heterozygous weaver embryos (high beta-glucuronidase activity, Gusb) with C3HAw wild-type embryos (low beta-glucuronidase activity, Gush). Chimeric cerebella were stained for beta glucuronidase activity and counts were made of the number of wv/- (Gusb) and +/+ (Gush) Purkinje cells. If the weaver gene acts intrinsically in the Purkinje cells, then the number of genetically wv/- and not +/+ Purkinje cells should be decreased. Alternatively, if the Purkinje cells are extrinsically affected by the weaver gene, then both wv/- and +/+ should be equally reduced. In this study, using comparative measures of chimerism and Purkinje cell numbers, only weaver Purkinje cells were reduced, while the +/+ Purkinje cells were unaffected in the chimera. These results indicate that the decrease in Purkinje cell number seen in the wv/wv and wv/+ cerebellum is a direct effect of the weaver gene. In concordance with previous work, the disorganization of the Purkinje cells in the cerebellum, however, results from an indirect effect of the weaver gene. PMID- 2331789 TI - Immortalized young adult neurons from the septal region: generation and characterization. AB - Studies of the development of the central nervous system would be greatly facilitated by the ability to immortalize neuronal tissue from a broad range of ages. We have previously used somatic cell fusion techniques to generate neuronal cell lines from embryonic mice. To immortalize older neuronal cells, a cell isolation technique was developed to obtain viable septal cells from postnatal day 21 mice. The septal cells were fused to N18TG2 neuroblastoma cells and then cultured in selective medium to isolate septum x neuroblastoma cell lines. The hybrid nature of the lines was verified by chromosome analysis and electrophoretic analysis of glucosephosphate isomerase isozymes. The lines express phenotypes typical of differentiated septal neurons. Many lines morphologically resemble neurons and express the high molecular weight neurofilament protein. Several lines express high levels of choline acetyltransferase activity; others synthesize nerve growth factor. These results demonstrate that young adult neuronal tissue can be immortalized and that hybrid cells express properties of the neuronal parent. PMID- 2331790 TI - Establishment of a long-term primary culture of striatal neurons. AB - A new method of obtaining long-term primary cultures (lasting more than 8 weeks) of striatal neurons is described in this paper. The originality of the method consists of: (1) starting the culture for 3 days in a serum-free medium which allows attachment and neurite proliferation of neurons as well as the death of non-neuronal cells (mainly consisting of astrocytes); (2) introducing a limited amount of fetal calf serum (FCS) (2-5%) after 3 days in vitro (3 DIV), which likely provides optimal neuronal survival and attachment factors, and a limited amount of astrocyte proliferating factors. The period of introduction of serum, as well as the amount of serum introduced are critical factors. By phase contrast and transmission electron microscopy, we observed that neurons continued to develop neurite extensions, synaptic vesicles and synapse formations up to 50 DIV. Neuronal membranes, and synaptic contacts were particularly healthy up to 50 DIV. Interestingly, the number of astrocytes was constant between 30-50 DIV and limited to about 10%. We therefore obtained an equilibrium between neuronal and astrocyte differentiation and proliferation. It is likely that the small population of astrocytes, plus the low percentage of FCS added, provide essential factors for neuronal survival and differentiation, whereas a high density of differentiated neurons inhibited astrocyte cell proliferation. The clear-cut stability of these neuronal cultures goes in parallel with the stability of the pharmacological responses studied here: the coupling of carbachol and quisqualate receptors with the inositol phosphate production system. The culture method described here could be of particular interest to pursue biochemical, pharmacological and biological studies on neurons as well as on reciprocal interactions between neurons and astrocytes. PMID- 2331791 TI - Fibroblast growth factor (FGF) levels in the developing rat brain. AB - Acidic and basic fibroblast growth factors (FGF) are polypeptides with potent multipotential trophic effects on central nervous system (CNS) glia, endothelial cells, and neurons. These factors are characterized by strong binding to heparin, and are commonly assayed by their mitogenic activity on Balb/c 3T3 cells in vitro. We found a marked (ca. 13-fold) increase in Balb/c 3T3 mitogenic activity in the developing rat brain from the embryonic stage to the third postnatal week. High levels were sustained in the mature brain. Most of the mitogenic activity from rat brain bound strongly to heparin-affinity columns, and was eluted at positions characteristic of acidic FGF (aFGF) and basic FGF (bFGF). The presence of aFGF and bFGF in eluted peaks was confirmed by immunoblotting techniques using specific anti-FGF sera. Heparin-affinity high performance liquid chromatography (HPLC) showed a proportionately greater increase in levels of aFGF than bFGF between the tenth and fortieth postnatal days. Increases in FGF levels during late embryonic and early postnatal stages of brain development may play an important role in the glial and capillary proliferation, as well as in the neuronal outgrowth and synapse formation that is occurring during this time. The differential rates of accumulation of aFGF vs bFGF suggest different physiological roles for these factors in the developing brain. PMID- 2331792 TI - Developmental changes in serotonin actions in rat hippocampus. AB - Intracellular activity was recorded from neurons in immature rat hippocampal slices. The presence of intrinsic inhibitory synaptic potentials as well as responses to serotonin were assessed in slices of 1, 2 or 3 postnatal weeks of age. Young (1 week) cells had only a marginal hyperpolarizing response to serotonin and no detectable intrinsic inhibitory synaptic potentials. At 2 weeks of age neurons already expressed a fast IPSP (inhibitory postsynaptic potential). The responses to serotonin were different from those of adult cells in that they involved primarily a large decrease in input resistance with only small potential changes. In cells of this age serotonin caused a marked increase in spontaneous IPSP discharges and a blockade of a slow afterhyperpolarization. In 3-week-old rats the fast and slow components of the IPSP were present as in adult and the responses to serotonin included a large hyperpolarization associated with an increase in K conductance, a blockade of slow afterhyperpolarization and a blockade of a slow IPSP, as seen in adult cells. These results indicate that the complex pattern of reactivity to serotonin is differentially regulated in the developing brain. PMID- 2331793 TI - Trophic effects of basic fibroblast growth factor on fetal rat hypothalamic cells: interactions with insulin-like growth factor I. AB - The existence of different growth factors within a single brain region suggests that developing brain cells are exposed to a variety of trophic factors throughout neurogenesis. Cooperative interactions between growth factors are known to orchestrate growth and differentiation of various cell types. We explored the possibility that two growth factors may interact in promoting in vitro growth in fetal hypothalamic cells. We found that basic fibroblast growth factor (b-FGF) exerts trophic effects on primary mixed hypothalamic cell cultures, on enriched hypothalamic neuronal cultures, and on hypothalamic glial cultures. In addition, b-FGF increased the growth rate of two virally transformed hypothalamic cell lines. Since insulin-like growth factor I (IGF-I) also promotes growth of rat hypothalamic cells in vitro, we examined the combined effects of b FGF and IGF-I on hypothalamic cells. Significantly higher numbers of neurite bearing cells were present in primary mixed hypothalamic cultures when b-FGF and IGF-I were added together than were added separately. The effect was additive. These results establish b-FGF as a putative hypothalamic neurotrophic factor and demonstrate potential coordinate interactions between IGF-I and b-FGF in stimulating the growth or survival of developing hypothalamic cells. PMID- 2331794 TI - A comparison of the initial retinal ganglion cell projection to the contralateral superior colliculus in albino and pigmented rats. AB - Newborn albino and pigmented rats received localised Fast blue (FB) injections into the most caudal part of the contralateral superior colliculus (SC). A proportion of retinal ganglion cells (RGC's) from the temporal retina which in the adult projects exclusively to the rostral half of the colliculus are labelled by injections to the caudal colliculus in neonatal animals. The majority of these cells die during the period of naturally occurring cell death in the retina, which occurs during the first 10 postnatal days. The object of this experiment was to see whether albino rats, which have well documented abnormalities in axon pathfinding in their visual system, had a larger number of cells in temporal retina which initially project to caudal colliculus than pigmented animals. On postnatal day 2 (P2), the ratio of temporal to nasal RGCs projecting to the caudal SC is greater in albino than pigmented rats (6.2% vs 2.65%). After the wave of naturally occurring cell death, at P14, when many of the neonatal errors have been eliminated, the ratio of temporal to nasal RGC's is reduced to 1.71% for albinos versus 1.53% for pigmented rats. PMID- 2331795 TI - Postnatal development of striatal dopamine function. I. An examination of D1 and D2 receptors, adenylate cyclase regulation and presynaptic dopamine markers. AB - We have characterized the postnatal development from 1 to 7 weeks after birth in rat striatal homogenates of D1 and D2 dopamine (DA) receptor sites, adenylate cyclase (AC) enzyme activity coupled to DA receptor function, guanine nucleotide binding sites and presynaptic markers of DA terminal function. D1 receptor density, expressed per unit of membrane protein, does not increase over this developmental interval, while maximum DA-stimulated AC activity per mg membrane protein increases 50-100%. D1 agonist affinity for D1 receptor sites doubles by 7 weeks of age but is consistently reduced by guanine nucleotide during development. Guanine nucleotide stimulation of AC develops a biphasic dose response curve after 3 weeks of age. Between 2 and 4 weeks postnatal age there is a rapid increase in AC catalytic component activity as manifested by the capacity of forskolin or manganese ion to stimulate AC in presence of guanine nucleotide and DA. Reversible [3H]GppNHp (guanyldiphosphonateimidophosphate) binding to striatal homogenates is dependent on Mg2+, inhibited by Ca2+ and GppNHp analogues, and occurs in about a 300-fold excess over D1 sites. Presynaptic markers of dopaminergic function indicate a 7-fold increase in tissue DA levels, a 2-fold reduction in DA turnover and no apparent change in density of DA uptake sites, assayed by [3H]mazindol binding. Subcomponents of D1 and D2 DA receptors have distinct postnatal developmental profiles. Striatal D1 sites do not change significantly during development, but D2 receptors and GTP inhibition of AC increase and appear, respectively, at 3-4 weeks of age, at the same time as the massive matrix innervation of striatum by DA terminals. PMID- 2331796 TI - Auditory brainstem of the ferret: maturation of the brainstem auditory evoked response. AB - A longitudinal study of developmental changes in the brainstem auditory evoked response (BAER) was made on 19 ferrets between postnatal days 25 (P25) and 50. Responses to free-field click stimuli were recorded from anaesthetized animals, and compared with data obtained from 8 adult ferrets. A reproducible BAER was first recordable on P27, although the response onset was generally later in smaller animals. BAER onset preceded eye opening, which started on P32. Adult like thresholds were observed in all animals by P40, but the age at which they were attained was also dependent on size. The BAER in the adult ferret consists of 4 main vertex-positive peaks occurring in the first 5 ms following transient acoustic stimulation. In the youngest animals the presence of an additional peak (between II and III) and the slurring of peaks III and IV were consistent features. The individual peaks undergo an asymmetrical pattern of development, with mean peak I latency attaining an adult value at P40, while mean peak IV latency is still 115% of the mean adult value at that age. BAERs could routinely be recorded using high stimulus presentation rates (greater than 40/s), though an increase in absolute and interpeak latencies occurred, the extent of which decreased with age. The pattern of BAER development in the ferret is compared with that in other species, and the concept of the 'silent period' (period between conception and onset of hearing) as a standard unit of auditory development is introduced. PMID- 2331797 TI - Development of vasopressin neurons in the human suprachiasmatic nucleus in relation to birth. AB - The number of neurons expressing vasopressin (AVP) was determined in the suprachiasmatic nucleus (SCN) of the hypothalamus of 41 human subjects ranging in age from 27 weeks of gestation up to 30 years of age. At term, i.e. at 38-42 weeks of gestation, the fetal SCN is still immature, since it then contains only about 13% of the adult number of AVP-expressing neurons. The period of rapid increase in the number of AVP-staining neurons in the SCN during the first few months postnatally coincides with the appearance of overt diurnal rhythms in the child. PMID- 2331798 TI - Are specific proteins implicated in the learning process of imprinting? AB - Day-old chicks were exposed for 0.5 h to overhead lighting ('primed') and then imprinted by exposing them for 90 min to a rotating red box. The chicks were otherwise maintained in darkness. Immediately after training these chicks (n = 16), together with 16 primed and 16 dark-reared controls were killed. Samples from the left cerebral hemisphere were removed including (i) the intermediate and medial part of the hyperstriatum ventrale (IMHV), a region which is crucial for imprinting, (ii) the posterior neostriatum and (iii) the visual Wulst. The samples were incubated with [35S]methionine, processed for SDS slab gel electrophoresis and autoradiographs prepared. The optical densities of various bands were measured 'blind'. For no band was there a significant interaction (ANOVA) between brain region and experience. Optical density was correlated with approach activity during training, a measure of behaviour which correlates with the amount chicks learn. Only for IMHV were correlations significant: a negative correlation (P less than 0.01) for approximately 50 kDa band and positive correlation (P less than 0.001) for an approximately 80 kDa band. These results suggest that associated with training there is a reduction and an increase in the synthesis of proteins in IMHV. PMID- 2331799 TI - Sequential appearance of anionic domains in the developing blood-brain barrier. AB - The distribution of anionic sites in the walls of mouse brain micro-blood vessels (MBVs) during development and maturation of the blood-brain barrier (BBB) was studied by electron microscopy. Cationic colloidal gold (CCG) and Lowicryl K4M embedded brain samples obtained from mouse fetuses (13th and 19th days) and from 1-, 5-, 12- and 24-day-old and adult mice were used. The labeling of anionic sites with CCG was more intense on the abluminal than on the luminal front of the endothelial cells (ECs) in fetuses and in newborn mice. Only a few anionic sites appear on the luminal front of the ECs of proliferating blood vessels invading the neural tissue in 13-day-old fetuses. They become slightly, although steadily, more abundant during further stages of development, and their number rapidly increases between the 12th and 24th day of life at which time they attain the density typical for mature animals. The maturation of the basement membrane (BM), which occurs during the myelinization period (12th-24th day of life), also coincides with an increasing concentration of anionic sites. These observations suggest that the gradual appearance of anionic sites on both fronts of the endothelium, as well as in the developing and maturing BM, represents one of the mechanisms responsible for differentiation of cerebral microvasculature into BBB type MBVs. PMID- 2331800 TI - Neuron migration within the radial glial fiber system of the developing murine cerebrum: an electron microscopic autoradiographic analysis. AB - The present analysis provides direct evidence in the mouse that in the course of course of neocortical histogenesis, contact between migrating neurons and the surfaces of radial glial fibers is both invariant and relatively selective. The analysis characterizes in detail the migratory behavior of the individual migrating cell with respect to the overall radial glial fiber system as this system varies systematically in its structure with ascent through the strata of the cerebral wall. A quantitative study of the relationships between the radial glial fibers confidently identified by their glycogen content and the migrating neurons marked autoradiographically by injection of [3H]thymidine was also performed at the ultrastructural level on tangential sections at different pallial levels in E16 and E17 embryos. The overall set of observations lend support to the hypothesis that radial glial fibers act specifically as guides to neuronal migration and illustrate the nature of the cell-to-cell interaction which serves this cellular process critical to neocortical histogenesis. PMID- 2331801 TI - Granule cell behavior on laminin in cerebellar microexplant cultures. AB - In order to study roles of the extracellular matrix (ECM) in the cerebellar granule cell migration, cerebellar microexplants of neonatal to postnatal 11-day old mice were cultured on 3 kinds of substrata, poly-L-lysine (PL), PL/fibronectin and PL/laminin. A prominent outgrowth of small granule cells, which did not uptake GABA, was observed only on the PL/laminin substratum. The granule cells showed the following sequence of events: (1) Many polygonal undifferentiated cells migrated out from the microexplants. These blast cells differentiated into small bipolar neurons with long fine neurites which extended radially from the explants. (2) These cells then changed their orientation perpendicular to their radial neurites, by protruding a short process from the cell body at right angles. (3) Finally, cell bodies of these granule cells adhered to each other to form cell aggregates. Quantitative labelings by bromodeoxyuridine revealed that there were less mitotic cells in explants from the later postnatal cerebellar compared to the earlier postnatal ones. Anti-MAP2 immunoreactivity was localized in short perpendicular processes of the aggregated granule cells. Thus, this unique cell behavior exhibited on the PL/laminin substratum provides the first defined experimental system for studying the granule cell differentiation in vitro. PMID- 2331802 TI - Rapid changes in 2-deoxyglucose uptake and amino acid incorporation following unilateral odor deprivation: a laminar analysis. AB - Unilateral naris occlusion in neonatal rats results in large alterations in the olfactory bulb, including substantial changes in laminar volume and enhanced cell death. These gross changes are undoubtedly the result of a cascade of more basic cellular regulatory events. The present study assesses the possibility of rapid post-deprivation changes in two such processes: glucose metabolism and protein synthesis. On the day after the day of birth rat pups underwent unilateral naris occlusion or sham surgery. In one study, either 1, 12, 24 or 48 h following surgery [3H]2-deoxyglucose [( 3H]2-DG) was administered to gauge patterns of glucose uptake. In a second study, [3H]leucine was injected to assess patterns of protein synthesis. Autoradiographs were then subjected to quantitative analyses. As early as 1 h following occlusion reduced 2-DG uptake was observed in many bulb regions. By 24 h, leucine incorporation was also uniformly diminished. While 2-DG uptake remained suppressed 48 h after deprivation, levels of amino acid incorporation returned to normal patterns in most laminae, with the exception of the mitral cell layer, where increased uptake was encountered. To evaluate whether the effects were developmental by nature a group of P40-P45 animals treated similarly were also examined. While 24 h of deprivation impaired 2-DG uptake in older animals, no alterations in amino acid incorporation were observed. The results indicate that early odor deprivation has rapid and specific effects on cellular functioning within the developing olfactory bulb. PMID- 2331803 TI - Development of GABAergic synaptic connections in vivo and in cultures from the rat superior colliculus. AB - Synaptic activity in the superficial (i.e. visual) layer of the superior colliculus was investigated with intracellular microelectrodes using a preparation of the isolated superfused tectum from neonatal rat. It was found that by postnatal day 9 (i.e. before eye opening) the majority of neurons in the superficial gray layer (SGS, stratum griseum superficiale) were already capable of generating Cl(-)-dependent inhibitory postsynaptic potentials (IPSPs) in response to intracollicular stimulation. Properties and development of GABAergic synaptic connections were further characterized in a dissociated cell culture from the SGS. The cultures were prepared from E21 rat embryos and studied between 1 and 38 days in vitro (DIV). gamma-[3H]aminobutyric acid ([3H]GABA) uptake served to identify GABAergic neurons and to estimate their relative density. Axon terminals were labeled by indirect immunostaining for glutamic acid decarboxylase (GAD) and examined with light (LM) and electron microscopy (EM). Responsiveness to exogenous and endogenous GABA was investigated by recording ionic currents with patch clamp techniques. [3H]GABA uptake-positive neurons constituted about 40% of the whole cellular population dissociated from the SGS of E21 rats. After 2 weeks in culture, [3H]GABA uptake was observed in 45-60% of the cells with neuronal features. The relative number of GAD-immunoreactive neuronal perikarya ranged from 28 to 39%, after 2 weeks in vitro. Responsiveness to exogenous GABA was found in all freshly plated neurons. Release of GABA could be demonstrated after 2 DIV by recording spontaneous bicuculline-sensitive Cl- currents. These currents had the characteristics of GABAA receptor-mediated synaptic currents. However, even as late as DIV 6, very few vesicle-containing axonal terminals apposing postsynaptic specializations were revealed with EM. GAD-labeled puncta became clearly visible only after DIV 10-12. Between DIV 14 and 21, the intensity of immunostaining and the density of GAD-labeled synaptic contacts increased, reaching a maximum around DIV 28. GAD-positive puncta covered both neurons and non-neuronal cells. At the level of EM, GAD-positive terminals were shown to establish synaptic contacts with neuronal somata and processes, forming in the majority of cases (22 out of 32 stained terminals) symmetrical contacts. It is concluded that in the SGS of the rat superior colliculus GABAergic neurons and GABAA receptors are present before birth. In dissociated cell cultures ionic currents can be generated in response to endogenous GABA before axonal terminals of GABAergic neurons fully mature. Finally, our experiments show that visual activity is not a prerequisite for the formation of GABAergic synapses between neurons of the SGS. PMID- 2331804 TI - Selected papers from the 4th Asian Pacific Congress of Clinical Biochemistry. Hong Kong, August 28-September 2, 1988. PMID- 2331805 TI - Humoral hypercalcemia of malignancy. AB - Studies on humoral hypercalcemia of malignancy have shown that tumors produce a protein that acts through the parathyroid hormone (PTH) receptor but is immunologically distinct from PTH. We have recently purified and cloned a parathyroid hormone-related protein (PTHrP) from a human lung cancer cell line. Full length cDNA clones were isolated and found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino terminal residues are identical with human PTH, although antisera directed at the amino terminus of PTHrP do not recognize PTH. A 34-amino acid synthetic peptide, PTHrP(1-34), was several times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of cAMP and plasminogen activity in osteogenic sarcoma cells and activation of adenylate cyclase in chick kidney membranes. PTHrP(1-34) was also more potent than PTH(1-34) in stimulating cAMP and phosphate excretion and reducing calcium excretion in the isolated perfused rat kidney. PTHrP has been consistently demonstrated by immunohistochemistry in squamous cell carcinomas and in keratinocytes present in normal skin, but not in normal or hyperplastic parathyroid tissues or other tumors. PTHrP-like activity has been extracted from ovine placenta and fetal parathyroid tissue, suggesting that PTHrP may play a role in fetal calcium homeostasis. PMID- 2331806 TI - Simultaneous determination of conjugated bile acids in human bile. AB - We describe an optimized liquid chromatographic method for simultaneous analysis of 10 conjugated bile acids in gall bladder and ductal bile. A quick and effective one-step purification with Sep-pak C-18 was adopted. We used a reverse phase C18 stainless steel column and an isocratic mobile phase in a flow programme and monitored the column effluent at 205 nm. The within-day CV ranged from 0.3 to 1.8%, and the between-day CV from 1.2 to 7.2%. Absolute analytical recovery ranged from 89 to 107%. Linearity ranged from 0.3 to 3 mg/mL for most bile acids. The chromatographic analysis was completed in 18 min. PMID- 2331807 TI - Oestrogen and progesterone receptors in men with bilateral or unilateral pubertal macromastia. AB - Abnormalities at the tissue receptor level may be important in the pathophysiology of pubertal macromastia, which may be unilateral or bilateral. We studied breast tissue removed from seven boys of age 16-17 years, five with bilateral and two with unilateral gynaecomastia. We confirmed that their physical features, karyotype, and plasma concentrations of testosterone, oestradiol, LH, FSH, and prolactin were all normal for adolescent males. Oestrogen and progesterone receptors were measured with a steroid binding (dextran coated charcoal) assay which was used for breast cancer receptor studies. Oestrogen receptors were not detectable in any of the 12 breasts studied. Progesterone receptors were detectable at a low level in two patients with bilateral gynaecomastia, one breast from each patient. We conclude that although the development of bilateral or unilateral male macromastia in puberty may yet be mediated by a local tissue receptor abnormality, this disorder is probably not mediated by an abnormal increase in oestrogen receptor number. PMID- 2331808 TI - The effects of submaximal endurance exercise upon LH pulsatility. AB - The acute effects of submaximal endurance exercise (three consecutive 20-min runs on a treadmill at 50, 60 and 70% of the subjects' maximum oxygen uptake) upon the pulsatile release of LH were compared with those accompanying leisurely strolling for a similar period in seven normally menstruating young women. All trials were conducted during the early to mid-luteal phase, as determined by body temperature patterns, ultrasonic scans of the ovaries, detection of the LH surge in first morning urine specimens, and serial measurements of plasma progesterone. Blood was sampled every 10 min via an indwelling cannula for 8 h before and 12 h after exercise and serum LH measured by radioimmunoassay. LH pulsations were analysed by a time series method. Following cannulation, mean LH levels declined but then rose to reach a maximum 2 h before the beginning of the exercise bout. LH concentrations remained virtually unchanged during exercise itself, and exhibited a declining trend throughout the post-exercise period. The findings in the two groups were similar in all respects, except that in the control study the rate of LH pulsatility was significantly diminished (P less than 0.05) during the first 2 h of sampling as compared with the subsequent 2-h period. The approximate half life of LH varied from 27 to 57 min, with a mean of 41 min. PMID- 2331809 TI - Secretory dynamics of oestradiol (E2) and progesterone (P4) during periods of relative pituitary LH quiescence in the midluteal phase of the menstrual cycle. AB - Although the temporal relationship between pulsatile pituitary luteinizing hormone (LH) secretion and steroid hormone release from the corpus luteum has been investigated, the secretory profiles of oestradiol (E2) and progesterone (P4) during periods without any discernible LH pulsatile activity remain unknown. Consequently, blood was sampled at 15-min intervals for 24 h from 16 women during the midluteal phases (6-8 days after midcycle LH surge) of their cycles. LH was measured in all samples and analysed for significant pulses by the Cluster pulse algorithm. Nine studies showing the lowest LH pulse frequencies and large LH pulse amplitudes were also assessed for E2 and P4 in all samples. All three hormones were released in pulsatile fashions. Pulses of E2 and P4 were found to be synchronous. While the release frequencies for E2 (mean +/- SEM: 8.9 +/- 0.7 pulses/24 h) and P4 (8.5 +/- 0.7 pulses/24 h) were comparable, the LH pulse frequency (4.6 +/- 0.4 pulses/24 h) was found to be significantly (P less than 0.001) lower than the ovarian steroid pulse frequencies. Maximum (P less than 0.01) cross-correlation coefficients were determined at positive time lags of 28.1 +/- 7.7 min for LH/E2 and 31.7 +/- 5.8 min for LH/P4, indicating that changes in E2 or P4 levels tended to occur within approximately 30 min following LH concentration changes. Further, the degree of concomitance between a steroid pulse and an LH peak was much higher (P less than 0.001) than by chance. Maximum (P less than 0.01) cross-correlation coefficients between E2 and P4 hormonal data series were found at zero time lag, suggesting that these sex steroids were secreted simultaneously. The pulse amplitudes, pulse durations and areas under the peaks of those E2 or P4 pulses preceded by large (greater than 5 IU/l) amplitude LH pulse were significantly greater (P less than 0.05 or less for all comparisons) than for steroid pulses not associated with preceding LH pulses. Thus, two populations of steroid pulses were observed; one associated with preceding LH pulses and having greater magnitude of all pulse attributes (duration, amplitude, area under the peaks), and another, not associated with preceding LH pulses and having pulse characteristics of lower magnitude. This observation suggests that the pulsatile release of ovarian steroids is a result of the episodic modulating influence of LH and that pulsatile steroid hormone secretion pertains with smaller magnitude during periods of relative pituitary quiescence of LH pulsatility. PMID- 2331810 TI - Hypothyroidism and thyroxine-induced liver damage. PMID- 2331811 TI - Effect of octapeptide somatostatin analogue (SMS 201-995) on plasma 7B2 (a neuroendocrine polypeptide) levels in patients with acromegaly. AB - We studied the sequential changes of plasma levels of immunoreactive '7B2' (IR 7B2), a neuroendocrine polypeptide, after a subcutaneous injection of 50 micrograms of synthetic octapeptide somatostatin analogue (SMS 201-995) in seven patients with acromegaly due to GH-producing pituitary adenoma. Compared to the basal levels, mean plasma IR-7B2 and GH levels significantly decreased, until 5 and 10 h respectively after the administration of SMS 201-995. The mean (+/- SEM) nadir levels of plasma IR-7B2 and GH were 68.1 +/- 10.1 and 13.1 +/- 6.9%, respectively, compared to mean plasma levels before treatment (100%). Plasma IR 7B2 as well as GH levels did not change significantly when saline was administered subcutaneously to three acromegalic patients. In addition, plasma IR 7B2 levels did not change significantly after the administration of SMS 201-995 in normal subjects or in patients with primary hypothyroidism in whom SMS 201-995 induced a decrease of plasma TSH levels. These results strongly suggest that SMS 201-995 has an unequivocal suppressive effect on the synthesis and/or the secretion of 7B2 in human somatotroph adenoma cells. PMID- 2331812 TI - Colon cancer and polyps in acromegaly: increased risk associated with family history of colon cancer. AB - A cohort of 52 subjects diagnosed with acromegaly in southeastern Michigan and northern Ohio between 1935 and 1985 were followed to determine the incidence of colon cancer and polyps. Medical records were reviewed, subjects or their next-of kin were interviewed, and screening examinations of the colon were offered to the living patients who were located. Data on demographics, personal histories of cancer and colon polyps, family history of colon cancer, and cure from acromegaly were obtained for both living and deceased subjects. The risk for colon cancer compared to the general population was estimated using standardized incidence ratios (SIRs). The expected number of cases was determined utilizing age, sex and race-specific rates provided by the cancer registry in southeastern Michigan. Among the 52 subjects, one could not be located and nine were deceased, none from colon cancer, with one known to have a history of colon polyps. Of 13 (31%) who declined the screening physical, one had a history of polyps and none reported a history of colon cancer. Two of 29 screened patients were found to have right sided adenocarcinoma of the colon. Of the entire cohort, eight people (including one deceased) had a current or previous diagnosis of polyps, with five known to be histologically adenomatous. The SIR for colon cancer was 4.7 (95% confidence interval 0.6-17.1). Seven subjects, including the two with detected adenocarcinoma and four of the six living subjects with polyps only, reported a family history of colon cancer. The SIR for the subset of subjects with a family history of colon cancer was 29.1 (95% confidence interval of 3.5-104.6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331813 TI - [In vitro immunoglobulin synthesis by peripheral blood mononuclear cells from patients with myasthenia gravis]. AB - In vitro immunoglobulin (Ig) synthesis was studied using peripheral blood mononuclear cells (PBM) from 12 patients with myasthenia gravis (MG). In cultured PBM, levels of secreted IgG, IgM and IgA measured by ELISA, as well as the number of IgG-, IgM-, and IgA-secreting cells determined by reversed plaque assay, were higher in MG than in controls; this was not dependent upon the stimulation of PBM with pokeweed mitogen (PWM). PBM from 9 of 12 MG patients synthesized anti acetylcholine receptor (AChR) antibodies in vitro in the presence of PWM, while PBM from 7 controls did not. Patients whose PBM secreted lower levels of each Ig class also secreted fewer or no anti-AChR antibodies. Levels of anti-AChR antibodies secreted in vitro showed a high degree of correlation with titers of sera from patients (r = 0.86). The results suggest that the process of anti-AChR antibody synthesis by PBM in vitro is related to that of Ig synthesis, and that PBM plays, at least in part, an important role in the production of anti-AChR antibodies in MG. PMID- 2331814 TI - [A case of hypothyroidism associated with hypokalemic periodic paralysis]. AB - A case of hypothyroidism associated with hypokalemic periodic paralysis was reported. The patient, a 50 year-old female was admitted because of recurrent paralytic attacks. She had not presented any symptoms of hypothyroidism. Physical examination on admission revealed muscle weakness of limbs, but not enlargement of thyroid glands. Paralytic attack was induced by oral intake of 100 g of glucose, and during attacks, serum K levels ranged from 3.4 to 3.0 mEq/l. She was diagnosed chronic thyroiditis by the high level of TSH and thyroid related anti antibodies in the serum. Muscle biopsy showed type II atrophy. After the improvement of thyroid function, her paralytic attack disappeared. Present study suggested that hypothyroidism could be a cause of hypokalemic periodic paralysis. This case was very rare and seemed important in etiology of periodic paralysis. PMID- 2331816 TI - [Cerebral white matter bundle alterations in patients with dementia of Alzheimer type and patients with multi-infarct dementia--magnetic resonance imaging study]. AB - The widths of the anterior white matter bundle (AWM) and the interhemispheric (AWM-TER) and intrahemispheric (AWM-TRA) bundles at the level of the foramen of Monro on horizontal inversion recovery MRI scans were measured in 17 patients with dementia of Alzheimer type (DAT), 16 patients with multi-infarct dementia (MID) and 47 age-matched normal subjects (NOR). The area of the corpus callosum (CC) on midsagittal spin-echo MRI scans was also measured in 12 DAT, 11 MID and 36 NOR. The Mini-mental score in patients with DAT was 20.8 +/- 5.9, which was not significantly different from that of 22.9 +/- 5.4 in patients with MID. The width of AWM was not significantly decreased in either DAT or MID compared with NOR. However, the width of AWM-TER in DAT and MID showed a significant decrease from that in NOR. The width of AWM-TRA was decreased significantly only in DAT. Compared with NOR, the area of the CC in DAT and MID was decreased by 7.0% (p less than 0.05) and 6.5%, respectively. The white matter bundle has an important role in the connectivity of the brain. Although loss of white matter occurs in both DAT and MID, the change appears more diffuse in DAT than MID. PMID- 2331815 TI - [Pindolol-induced rhabdomyolysis in sarcoid myopathy]. AB - A 72-year-old man suddenly developed severe muscle weakness following the treatment with pindolol (Calvisken) for three days. Neurological examination on admission disclosed marked proximal muscle weakness with absent deep tendon reflexes. Laboratory data showed significant increase of serum CK, aldolase and myoglobin. Electromyography revealed both neurogenic and myogenic changes in all muscle tested. Skeletal muscle CT showed patchy low density areas in muscles of thigh and leg, especially in the hamstrings. Femoral muscle biopsy demonstrated a granulomatous nodule with multinucleated giant cells in the degenerated muscle fibers showing small-grouped atrophy. By Mb-PAP staining, Mb-negative fibers were randomly distributed among normally stained ones. Leu 1, 3a, 4, HLA-DR positive cells were found adjacent to the granuloma by immunoperoxidase staining. After immediate withdrawal of pindolol and treatment with steroid, he recovered muscle strength and enzyme activities were normalized in a week. Beta blockers have been known to induce muscle cramps or pain and moderate elevation of serum muscle enzymes. However, severe muscle weakness with highly elevated enzyme activities leading to rhabdomyolysis as noticed in the present case was rarely reported in the literature. Underlying sarcoid myopathy might be suspected to exaggerate this unusual case of pindolol-induced rhabdomyolysis. A careful use of pindolol is emphasized. PMID- 2331817 TI - [Micrographia due to the lesions around basal ganglia and genu of internal capsule and dysarthria-clumsy hand syndrome]. PMID- 2331818 TI - [MRI study of hemiballism]. AB - MRI findings of four hemiballism cases are described, and pathophysiology, pathogenesis and treatment of hemiballism are discussed. All cases had no family history. The lesions revealed by MRI and the pathogenesis were different each other. Case 1, a 17 years aged girl with a history of hyperthyroidism and repeated tonsillitis, showed right sided hemiballism which was recovered by prednisolone and haloperidol. Although her involuntary movement was ameliorated by administration of sodium valproate and phenytoin, phenytoin caused allergic agranulocytosis which required prednisolone treatment. T2 weighted MRI at the 31st disease day demonstrated hyperintensities in the left caudate nucleus, putamen, lateral pallidum, perirubral area and substantia nigra. Hyperintensity in the prerubral area suggested involvement of the subthalamic nucleus or its connecting pathway. Fourteen months later, she suffered from convulsion and mental confusion. There were theta wave bursts and delta waves in EEG. No abnormal findings in MRI and positive antinuclear antibody (ANA: X320, speckled type) were observed. Case 2, a 78 year aged woman, suffered from right sided hemiballism. MRI findings at the 58th disease day were the left putaminal infarction and lacunar state in the bilateral caudate nuclei and the deep white matter of the centrum semiovale. There were no abnormal findings in the subthalamic nucleus. Case 3, a 51 year aged man with diabetes mellitus, had right sided hemiballism. X-ray CT at the 8th disease day showed hyperdensity in the left subthalamic nucleus region which could not be observed at the 12th day. Hypointensity in the left subthalamic nucleus region was observed in both T2 weighted and proton density MRI at the 52nd day. Case 4, an 82 year aged woman, had right sided hemiballism which remarkably diminished at the third disease day and disappeared by the fifth day. Any pathogenic lesion concerning to hemiballism was detected by X-ray CT or MRI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331819 TI - [Computed tomography of skeletal muscles in myotonic muscular dystrophy]. AB - The computed tomography (CT) of skeletal muscles was performed on 12 patients with myotonic muscular dystrophy (MyD). We have sliced at seven levels; those are 1. neck level-at the level of thyroid cartilage 2. shoulder girdle level-at the level of upper edge of sternum 3. upper arm level-at the level of middle of upper arm 4. abdominal level-at the level of L3 vertebra 5. pelvic girdle level-at the level of middle inguinal ligament 6. thigh level-at the level of middle of thigh 7. lower leg level-at the maximum size level of lower leg. The characteristic changes of MyD are; the sternocleidomastoid muscles are most severely affected, and the paravertebral and straight abdominal muscles also tend to be severely atrophied with lower CT density. Concerning thigh levels, the deeply located muscles and muscles for extension are predominantly affected. At the lower leg levels, the calf muscles are severely affected. The muscles of levator scapulae, trapezius, psoas major, iliopsoas, gluteus, and tibialis posterior tend to be preserved. In the tight, the compensatory hypertrophy is observed often in the rectus femoris muscles and rarely in the gracilis muscles with the involvements of the agonist muscles. It might be also important to examine the changes of muscles as a whole and to know the grade of atrophy for planning the life style. The CT examination would be recommended by this standpoint. PMID- 2331820 TI - [Changes in plasma norepinephrine levels to stepwise tilting--comparisons between the young and aged]. AB - Plasma norepinephrine level was measured in the 9 young (22-26 years old) and the 8 aged (66-81 years old) normal volunteers in stepwise tilting. After 30 minutes rest in recumbent position, the table was tilted in stepwise manner (15 degrees, 30 degrees, 45 degrees, 80 degrees) each for 5 minutes and blood samples were taken at the end of the each angle. The changes of the level was compared between the two groups and with the data resulted from the examination of muscle sympathetic activities by microneurography. The norepinephrine level increased with the stepwise tilting and the positive linear correlation was observed between the levels and the sine values of tilting angles. The absolute levels in the aged were significantly higher than those in the young in 0 degrees, 15 degrees, and 30 degrees. The increasing rates of plasma norepinephrine (percentages of increase against the level in 0 degrees position) in the aged were significantly lower than those in the young in 45 degrees and 80 degrees. These partly resembled the character observed in the two groups in muscle sympathetic activity. However, the gradients of the mean regression lines of the two groups in plasma norepinephrine level were not significantly different, although they were clearly different in muscle sympathetic activity. This means that the difference between the young and the aged was more clearly shown in muscle sympathetic activity than in plasma norepinephrine level. PMID- 2331821 TI - [Impedance plethysmographic evaluation of sympathetic activity to lower extremity]. AB - Impedance plethysmographic analysis was performed in two cases of late cortical cerebellar atrophy (LCCA) and two cases of Shy-Drager syndrome. Blood pressure, heart rate and peripheral hemodynamics (arterial blood flow and vascular resistance of lower extremity) were measured during head-up tilting. In cases of LCCA, there was no decrease of blood pressure by tilting up. Impedance plethysmography showed significant increase in vascular resistance of lower extremity and heart rate was also increased. In cases of Shy-Drager syndrome, however, marked decrease of blood pressure was shown during tilting up, while there was no significant change in heart rate and vascular resistance of lower extremity was decreased. Therefore, in cases of Shy-Drager syndrome, decrease of peripheral sympathetic activity to lower extremity was suggested. Impedance plethysmography of lower extremity is simple, non-invasive and useful method to assess the status of peripheral sympathetic activity. PMID- 2331822 TI - [Assay of nuclear triiodothyronine receptors in the precentral gyrus in patients with amyotrophic lateral sclerosis]. AB - Abnormality in the receptor of the cell might have some bearing on the selective cellular damage in systemic degenerative diseases. In relation to deranged metabolic turnover of the folate cycle in amyotrophic lateral sclerosis (ALS), we have measured nuclear triiodothyronine receptors (NT3R) in the precentral gyrus, stored at -80 degrees C after autopsy, of 4 ALS patients and 8 patients with non neurological diseases. Cell nuclei were separated in bulk from about 1 g of grey matter by the method of Lovtrup-Rein & McEwen, and T3-binding assay was carried out by the method of Silva et al. DNA was measured by the method of Giles & Myers based on Burton's method. Specific bindings comprised more than 85% of total bindings. Scatchard analysis showed that the maximal binding capacity, namely the density of NT3R was significantly reduced in ALS, compared to that of the controls. The dissociation constant, namely the affinity was not different between the two groups. The present investigation suggests that NT3R may be reduced in the motoneuron of ALS patients, although the result might merely indicate the loss of nerve cells from the ALS motor cortex. This point should be clarified, but the bulk separation of pure nerve cell nuclei from autopsied human brain has not so far been successful in our laboratory. Action of thyroid hormone in the mature brain has not fully been clarified. Meanwhile, some investigators suggest that the metabolic state of the central nervous system of ALS has a tendency of hypothyroidism. Therefore, the relevance of thyroid hormone to pathogenesis or pathophysiology of ALS will be an important subject in future study. PMID- 2331823 TI - [A case of neurovisceral storage disease with sea-blue histiocyte and severe horizontal supranuclear ophthalmoplegia]. AB - Neville and coauthors (1973) reported several cases of neurovisceral storage disease with vertical supranuclear gaze paresis, ataxia and other central nervous disorders. This disease is classified into Niemann-Pick disease type C because of the presence of foamy cells or sea-blue histiocytes in bone marrow, and the accumulation of sphingomyelin, cholesterol and other glycosphingolipids. In this paper, we reported a rare case of neurovisceral storage disease with severe horizontal supranuclear ophthalmoplegia and sea-blue histiocyte in bone marrow. The patient was a 9-year-old boy. He was hospitalized for unstable gait. The neurological examination revealed severe horizontal supranuclear ophthalmoplegia, moderate ataxia of four extremities and trunk, and mild dystonia of neck and four limbs on walking and standing. The ocular movement in the vertical direction was less impaired and his mentality was almost normal. The bone marrow aspiration showed a few sea-blue histiocytes. The activities of fibroblast lysosomal enzymes including sphingomyelinase were normal. The rectal biopsy revealed many foamy cells in mucous membrane and submucosa. The cell had PAS-positive and acid phosphatase-positive substances, which showed rose-red metachromasia with Feyrter's thionin method. But these abnormal cells were never stained by Sudan black B. These histochemical reactions were compatible with those of Neville's neurovisceral storage disease (Lake, 1983). Therefore we supposed the pathogenesis of this case was the same as that of Neville's cases. In this case, the horizontal supranuclear ophthalmoplegia was a unique symptom. PMID- 2331824 TI - [Neuroradiological studies of Wilson's disease by computed tomography and magnetic resonance imaging]. AB - Three cases of Wilson's disease were imaged by computed tomography and magnetic resonance. They were characterized by common findings. CT scan showed atrophy of cerebral cortex, caudate head, midbrain and cerebellum, and areas of low absorption in the caudate head, putamen, globus pallidus, posterior limb of internal capsule, thalamus and midbrain. The T2-weighted MRI imaging demonstrated marked hyperintensity in the putamen, retrolenticular part of internal capsule, thalamus and midbrain. In 2 patients, these high intensity areas were decreased by chelating therapy. Improvement of the increased intensity on T2-weighted images led to the suggestion that the area of marked hyperintensity area might be edema or demyelination rather than neuronal loss or cavitation. PMID- 2331825 TI - [Left-sided extremity myorhythmia and rightward slow eye movement caused by a hemorrhage in the right pontine tegmentum]. AB - A sixty-year-old man was admitted to our hospital on January, 1989. He had suffered a hemorrhage in the right side of pontine tegmentum on April, 1988. He had been in deep coma for about a week, and then he had showed diplopia, mild right deafness, right facial palsy, left hemiparesis, dysarthria, dysphagia, and urinary disturbance. He showed slight improvement of these symptoms and signs, but had developed thereafter extremity myorhythmia on the left side. On admission, rightward slow eye movement (absence of saccadic eye movement and preservation of pursuit eye movement of both eyes) was present. MRI revealed a hypointensity lesion with a hyperintensity spot on T2-weighted images showing an old hemorrhage in the right pontine tegmentum and a hyperintensity lesion on T2 weighted images showing an olivary pseudohypertrophy on the right. We concluded that the extremity myorhythmia in this patient was caused by the damage of the right central tegmental tract followed by right olivary pseudohypertrophy. The rightward slow eye movement was considered to be due to the damage of the right paramedian pontine reticular formation and/or its afferent fibers in the pontine tegmentum. PMID- 2331826 TI - [A case of "neuralgic amyotrophy" with elevated serum antibody titer against Borrelia burgdorferi]. AB - A 39-year-old man experienced an abrupt onset of right back pain. The pain improved spontaneously, but weakness of the right upper extremity developed. The weakness deteriorated during the next month, and he was admitted to our hospital. Neurological examination disclosed impairment of superficial sensation in his right upper extremity. Blood examination showed no abnormal data. The cerebrospinal fluid was normal. Neuroradiological findings were also negative. Electrophysiological examinations were normal except for needle electromyographic findings of the right upper extremity, which showed neurogenic patterns of moderate degree. Those findings suggest neuralgic amyotrophy. However, examining the serum sample significantly elevated levels of antibody titers against Borrelia burgdorferi were observed, and we suspected that his illness was Lyme disease. He recalled, however, no arthropod bite. Neuralgic amyotrophy is a syndrome which takes a characteristic clinical course. It includes some heterogeneous disorders. On the other hand, Lyme disease, a tick-transmitted spirochetal illness, occurs in stages, with remissions and exacerbations and different clinical manifestations at each stage. The neurological abnormalities include aseptic meningitis, encephalitis, cranial neuritis, motor and sensory radiculitis, and myelitis in various combinations. They can be diagnosed serologically. However, it is possible that elevation levels of the antibody titers mean nonspecific damages of peripheral nerves. Further study is necessary to decide whether cases like ours suffer from so-called Lyme disease or not. PMID- 2331827 TI - [A case of polymyositis associated with primary biliary cirrhosis]. AB - We studied a 67-year-old female suffered from polymyositis associated with primary biliary cirrhosis. She was pointed out liver dysfunction by screening test. Alkaline phosphatase, transaminase, and IgM were increased. Antimitochondrial antibody and antinuclear antibody were positive. Liver biopsy showed cell infiltrations in Glisson's capsules and destruction of cholangioles, being diagnosed as primary biliary cirrhosis (Scheuer Stage I). Four years later she showed a muscle weakness of four extremities and admitted to our department. Neurological examination revealed a severe weakness and atrophy of both proximal and distal muscles. Deep tendon reflex was decreased on four extremities. Laboratory examination showed a creatine kinase level of 312 IU/L, alkaline phosphatase 238 IU/L, gamma-glutamyl-transpeptidase 140 IU/L, Igm 416 mg/dl, antimitochondrial antibody titer 1:320, and antinuclear antibody titer 1:320. Muscle biopsy findings were compatible with polymyositis. Electron microscopic examination disclosed diffuse increase of mitochondria in subsarcolemma and intermyofibrils. Until now eight cases with polymyositis associated with primary biliary cirrhosis have been reported, but electron microscopic examination of muscle has not been carried out. It is necessary to examine mitochondria of muscle and liver in patients with polymyositis associated with primary biliary cirrhosis for the elucidation of its etiology. PMID- 2331828 TI - [Harlequin syndrome (unilateral flushing and sweating attack) due to a spinal invasion of the left apical lung cancer]. AB - A 54-year-old man was admitted to our hospital because of a persistent pain of the left cervix and scapular region of three-month duration and an abnormal shadow in the chest roentgenograms. Neurological examinations, chest roentgenograms, chest CT scanning, vertebral tomograms and myelogram revealed Pancoast's syndrome concomitant with Horner's syndrome. Four months later, the patient complained of a sudden onset of unilateral flushing and sweating appearing on the right face, cervix and upper chest. Eye drop tests with cocaine, epinephrine and tyramine indicated the lesion of ciliospinal centers between the 8th cervical and 2nd thoracic spines. The unilateral flushing and sweating attack appearing on the intact side without Horner's syndrome seemed to be an excessive response by an intact sympathetic pathway, the other side failing to respond because of a sympathetic deficit. PMID- 2331829 TI - Detection of young children in need of reading help. Evaluation of specific reading disability formulas. AB - To determine whether formula-based definitions of specific reading disability (SRD) were related to the actual classroom performance of children aged 7 1/2, the authors applied five definitions of SRD to a cohort of 243 children. The children were followed from birth and not selected on the basis of cognitive, reading, or academic performance criteria. The authors determined the concurrent validity of each of the formulas by comparing the prediction of each definition to whether the child received additional reading help in the classroom. Although the years behind method was significantly better than other approaches, no method identified more than 48 percent of the children who were given additional reading help. This study questions the ability of formula-based definitions adequately to identify young children with reading dysfunction. PMID- 2331831 TI - Use of blood components. PMID- 2331830 TI - Comparison of urine dipstick, microscopy, and culture for the detection of bacteriuria in children. AB - The authors compared dipstick tests for leukocyte esterase and nitrite and microscopic examination of urinary sediment with urine culture to assess whether the former tests could reliably rule out bacteriuria in specimens from children. The authors studied urine specimens from 1010 infants and children younger than age 18. Compared with culture at greater than or equal to 10(5) colony forming units (cfu)/ml, the sensitivities of leukocyte esterase, nitrite, and microscopic examination of white blood cells (greater than or equal to 5 wbc/hpf) or bacteria (in at least moderate numbers) were 76 percent, 29 percent, 82 percent, and 80 percent, respectively. The specificities of the same tests were 81 percent, 99 percent, 81 percent, and 83 percent, respectively. Compared with culture at greater than or equal to 10(4) cfu/ml, the sensitivities of the tests were 64 percent, 21 percent, 64 percent, and 59 percent; the specificities were 82 percent, 99 percent, 81 percent, and 83 percent, respectively. The negative predictive values of leukocyte esterase and microscopic examinations of urinary sediment for white blood cells and bacteria were all 95 percent (greater than or equal to 10(4) cfu/ml) or 98 percent (greater than or equal to 10(5) cfu/ml). The authors conclude that the leukocyte esterase test is as accurate as sediment microscopy in identifying urine specimens from infants and children harboring less than 10(4) or less than 10(5) cfu/ml. PMID- 2331832 TI - Neonatal ABO incompatibility. Complicated by hemoglobinuria and acute renal failure. AB - The authors present two infants with isoimmune hemolytic disease due to ABO incompatibility complicated by massive hemoglobinuria and secondary acute renal failure. This represents an incidence of 0.36% of all neonates with ABO hemolytic disease in the author's newborn population. Only two patients have been reported previously to have similar complications. Analysis of data of these four infants revealed the clinical characteristics of this complication of ABO incompatibility: 1) very low frequency; 2) early onset of hemoglobinuria (first voided urine) and of acute renal failure (first 2 days of life); 3) lack of correlation between the clinical presentation of hemolytic disease and appearance and severity of renal failure; 4) complete recovery of renal functions following intravenous fluid administration; and 5) normal renal radiologic investigations. PMID- 2331833 TI - Precautions necessary with central venous catheters. PMID- 2331834 TI - Aerosolized pentamidine for Pneumocystis carinii pneumonia. PMID- 2331835 TI - Safety alert on homemade solutions for contact lens care. PMID- 2331836 TI - Massive systemic and intracranial air embolism in a very premature infant. PMID- 2331837 TI - Seizure following oral rehydration of hypernatremia with water. PMID- 2331838 TI - Late presenting, prolonged hypocalcemia in an infant of a woman with hypocalciuric hypercalcemia. AB - Familial hypocalciuric hypercalcemia (FHH) is a benign autosomal dominant disorder. Infants affected with FHH however, born to unaffected mothers may develop life-threatening autonomous hyperparathyroidism, the mechanism of which is not clearly understood. There is little information recorded in the literature regarding the opposite scenario, i.e., unaffected infants born to affected mothers. Because fetal parathyroid suppression presumably occurs secondary to high maternal calciums, neonatal hypocalcemia would be expected. The authors present a case of an infant with the latter circumstances who presents with late onset, life-threatening hypocalcemia secondary to relative hypoparathyroidism. The authors explored the possibility that vitamin D deficiency and/or acute environmental stress facilitated the decompensation. The patient required therapy for 2 months. PMID- 2331839 TI - Otitis media in practice. A different approach to management. Commentary from clinical observation. PMID- 2331840 TI - Colorado Cancer Registry. PMID- 2331841 TI - Desktop medicine. PMID- 2331842 TI - Meperidine for prevention of amphotericin B-induced chills. PMID- 2331843 TI - Inability of inline pressure monitoring to predict or detect infiltration of peripheral intravenous catheters in infants. AB - Monitoring of inline intravenous pressure as a method for predicting or detecting infiltration of peripheral catheter sites in infants was evaluated. Inline intravenous pressure was measured every 30 minutes in infants less than 12 months of age who had standardized peripheral catheters through which they were receiving a continuous infusion. Pressure was measured by an inline pressure transducer, and the signal was recorded by a strip chart recorder. Physical activities or manipulations of the patients were recorded simultaneously with each pressure reading. The catheter site was inspected hourly for clinical signs of infiltration. There was no significant difference in baseline or final pressure measurements between patients whose catheter sites became infiltrated (n = 20) and patients whose catheter sites did not (n = 22). Likewise, changes in pressure from baseline did not differ between the infiltrated and noninfiltrated groups. At 12 hours before the final reading, pressures for the infiltrated group did not differ significantly from pressures for the noninfiltrated group, nor did these values differ from the respective baseline values. Over the final 12 hours of catheterization, mean slopes (changes in pressure over time) for the two groups did not differ significantly from 0 or from each other. Intrapatient specificity and sensitivity of the method and the false-alarm rate were clinically unacceptable. Monitoring of inline intravenous pressure is not useful for predicting or detecting infiltration of peripheral catheter sites in infants. PMID- 2331844 TI - Effect of serum separator tubes on serum quinidine concentration measurements. PMID- 2331845 TI - Tumor markers in diagnostic pathology. PMID- 2331846 TI - RNA homology and the reclassification of Pneumocystis. AB - The identification of sequence similarities in ribosome RNA subunits from Pneumocystis and certain fungi has led to the suggestion that this presumed protozoan be reclassified as a fungus. However, the absence of predictable characteristics from the fungi as a group to Pneumocystis as a genus indicates that we should wait until additional rRNA coding sequences of more organisms have been compared. PMID- 2331847 TI - A comparison of oxoid signal with nonradiometric BACTEC NR-660 for detection of bacteremia. AB - The Oxoid Signal (Oxoid U.S.A. Inc., Columbia, Maryland) system was compared with the nonradiometric BACTEC NR-660 (Johnston Laboratories, Towson, Maryland) system for detection of bacteria in 2714 blood cultures. The volume of blood collected into 20 ml blood-collection tubes containing sodium polyanetholsulfonate (SPS) (Becton Dickinson, Vacutainer Systems, Rutherford, New Jersey) ranged from 10 to 20 ml with an average of 15 ml. Subsequently, equal volumes of blood were inoculated into each system. A total of 250 organisms was isolated (9.6%), of which 149 (5.5%) were considered significant while 111 isolates from 98 cultures (3.6%) were contaminants. Of the significant isolates 32.9% were aerobic Gram negative rods, 53.0% aerobic Gram-positive cocci, 5.4% anaerobes, 7.4% yeasts, and two isolates of Neisseria meningitidis. Ninety-five isolates were recovered in both systems, 29 by Bactec only and 25 by Signal only. Of the isolates recovered there were no significant differences in detection between the two systems with the exception of anaerobes (p less than 0.005). The median detection times for many of the most commonly isolated organisms--Enterobacteriaceae, streptococci, and Staphylococcus aureus--were very similar in both systems, ranging from 14 to 21 hours. With the remaining organisms recovered, the median times in hours for BAC-TEC and Signal, respectively, were 31 and 47 for Staphylococcus epidermidis, 48 and 60 for Bacteroides, 39 and 168 for yeast, and 16.5 and 168 for N. meningitidis. Oxoid Signal compares favorably with the BACTEC system. Its main advantages are: (1) it requires no instrumentation; (2) it is characterized by ease of detection; and (3) it uses a single-bottle system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331848 TI - Increasing usage of systemic antifungal agents. PMID- 2331849 TI - Comparative in vitro activity of cefoperazone and various combinations of cefoperazone/sulbactam. AB - Cefoperazone with 2 and 4 micrograms/ml of sulbactam and in a 2:1 ratio was tested against 1258 clinical isolates of Gram-positive and Gram-negative bacteria, as well as against Gram-negative bacilli that had stably derepressed Type I beta-lactamase or that were hyperproductive of non-Type I beta-lactamases. The 2:1 cefoperazone/sulbactam combination was the most potent combination tested. With this combination cefoperazone minimum inhibitory concentrations (MICs) of 27 of 40 (67%) of the clinical isolates of Pseudomonas species and 64 of 67 (95%) of clinical isolates of the Enterobacteriaceae were reduced from greater than or equal to 64 micrograms/ml by at least two-fold. In contrast, cefoperazone MICs of greater than or equal to 64 micrograms/ml remained unchanged for 26 (65%) and 24 (60%) of Pseudomonas species and 35 (52%) and 30 (45%) of the Enterobacteriaceae in the presence of 2 and 4 micrograms/ml of sulbactam, respectively. Cefoperazone/sulbactam in the 2:1 ratio was also the most active combination against the mutants derepressed for Type I beta-lactamase. Although the 2:1 combination of cefoperazone/sulbactam had the greatest potency in vitro, it remains to be seen whether this combination is predictive of clinical outcome from treatment of cefoperazone-resistant Gram-negative bacilli with cefoperazone/sulbactam. PMID- 2331850 TI - In vitro activity of cefoperazone/sulbactam and other antimicrobials against anaerobic bacteria. AB - Sulbactam inhibits the hydrolytic activity of several, clinically important beta lactamases including those produced by anaerobic bacteria. This study was undertaken to determine the effect of sulbactam on the activity of cefoperazone against 250 anaerobic bacteria including 174 isolates belonging to the Bacteroides fragilis group and to compare the activity of cefoperazone/sulbactam with other antimicrobial agents. beta-lactamase activity was detected in 98% of the isolates of the Bacteroides fragilis group but not in the other species evaluated. Antagonistic activity between cefoperazone and sulbactam was not observed with any of the species. Forty-two percent of the isolates belonging to the B. fragilis group were resistant to cefoperazone. Ninety-four percent of these were converted to either the susceptible or moderately susceptible range upon the addition of sulbactam. Sixty-seven percent were susceptible to the combination cefoperazone/sulbactam and 27% were moderately susceptible. Overall, metronidazole and chloramphenicol were the most active antimicrobials. Significant differences in the antimicrobial susceptibility patterns of members of the B. fragilis group were observed. Sulbactam demonstrated some intrinsic activity against all of the species tested. PMID- 2331851 TI - In vitro activity of meropenem (SM-7338), imipenem, and five other antibiotics against anaerobic clinical isolates. AB - The in vitro susceptibility of 513 recent anaerobic clinical isolates was evaluated against meropenem (SM-7338), a new carbapenem, and six other antibiotics. Virtually all Gram-positive and Gram-negative anaerobic bacteria tested were susceptible to meropenem (defined as MICs less than or equal to 8 micrograms/ml) with 99.8% of the isolates inhibited by less than or equal to 4 micrograms/ml. The activity of meropenem was comparable to imipenem for most clinical isolates. Minor differences were observed for Clostridium and Veillonella (meropenem more active) and other Gram-positive bacilli (imipenem more active). Meropenem inhibited all anaerobes resistant to clindamycin and metronidazole. Bactericidal tests performed with meropenem demonstrated killing activity against all isolates except Clostridium and Lactobacillus. PMID- 2331852 TI - Optochin-resistant variants of Streptococcus pneumoniae. AB - Ten Streptococcus pneumoniae clinical isolates, possessing physiologically typical pneumococcal characteristics, showed optochin-susceptible and optochin resistant colonies around the optochin disk, when tested for optochin susceptibility. Equivocal optochin disk test results should be confirmed by bile solubility, agglutination tests, or both. PMID- 2331853 TI - Activity of cephalosporins against coagulase-negative staphylococci. AB - Staphylococcus epidermidis has become an increasingly important pathogen as the cause of serious postoperative infection after heart and orthopedic surgery. We studied the susceptibilities of 80 blood, sternotomy, and hip isolates to vancomycin, cefazolin, cefuroxime, oxacillin, erythromycin, ciprofloxacin, and ofloxacin. The MIC90 of methicillin-susceptible isolates was 4 micrograms/ml for cefazolin and cefamandole, 8 micrograms/ml for cefuroxime, and 4 micrograms/ml for vancomycin. At 48 hr the MIC90 rose to 32 micrograms/ml for cefazolin and greater than 128 micrograms/ml for cefuroxime, and remained at 4 micrograms/ml for cefamandole and vancomycin. The MIC90 of methicillin-resistant isolates at 48 hr was 16 micrograms/ml cefamandole, 64 micrograms/ml cefazolin, greater than 128 micrograms/ml cefuroxime, and 4 micrograms/ml vancomycin. Ciprofloxacin and ofloxacin inhibited the majority of isolates at 1 microgram/ml, and vancomycin at 4 micrograms/ml. The new peptolide, daptomycin, also inhibited S. epidermidis at less than or equal to 1 microgram/ml. PMID- 2331854 TI - Lomefloxacin (SC-47111 or NY-198). Comparative antimicrobial activity against 2002 clinical isolates from hospitals in Mexico City. AB - A new difluorinated quinolone, lomefloxacin, was shown to have potent in vitro activity against a broad spectrum of bacteria, including multiresistant strains isolated from patients with severe infections in three hospitals in Mexico City. Whereas its activity was comparable to that of another fluoroquinolone (enoxacin), the pharmacokinetic advantages offered by lomefloxacin may be a significant benefit in clinical use. PMID- 2331855 TI - Beta-lactam susceptibility of coagulase-negative staphylococci causing catheter sepsis in pediatric patients. AB - We evaluated standard oxacillin and methicillin disk diffusion (DD) and broth microdilution (MD)-MIC tests with and without 2% NaCl for detecting heteroresistance among 47 blood isolates of coagulase-negative staphylococci (CNS) causing catheter sepsis in pediatric patients. The 24-hr oxacillin DD test detected the greatest number (40) of apparent hetero-resistant isolates, but methicillin DD and oxacillin MD-MIC with 2% NaCl performed equally as well (38 and 37 resistant isolates, respectively). An additional 24-hr incubation did not significantly increase the number of apparent heteroresistant isolates detected by these methods. Discrepant results with the various test methods occurred most commonly among Staphylococcus epidermidis isolates with MD-MIC values near the breakpoint concentrations for interpretation of susceptible and resistant strains. For detection of heteroresistance among the CNS, we encourage use of standard oxacillin DD and MD-MIC tests but would suggest that isolates with MIC values ranging from 1-2 micrograms/ml be interpreted cautiously until clinical studies demonstrate the efficacy of treating patients with infections caused by such strains. PMID- 2331856 TI - Short-term memory coding by deaf signers: the primary language coding hypothesis reconsidered. AB - Shand (Cognitive Psychology, 1982, 14, 1-12) hypothesized that strong reliance on a phonetic code by hearing individuals in short-term memory situations reflects their primary language experience. As support for this proposal, Shand reported an experiment in which deaf signers' recall of lists of printed English words was poorer when the American Sign Language translations of those words were structurally similar than when they were structurally unrelated. He interpreted this result as evidence that the deaf subjects were recoding the printed words into sign, reflecting their primary language experience. This primary language interpretation is challenged in the present article first by an experiment in which a group of hearing subjects showed a similar recall pattern on Shand's lists of words, and second by a review of the literature on short-term memory studies with deaf subjects. The literature survey reveals that whether or not deaf signers recode into sign depends on a variety of task and subject factors, and that, contrary to the primary language hypothesis, deaf signers may recode into a phonetic code in short-term recall. PMID- 2331857 TI - Modeling the role of parallel processing in visual search. AB - Treisman's Feature Integration Theory and Julesz's Texton Theory explain many aspects of visual search. However, these theories require that parallel processing mechanisms not be used in many visual searches for which they would be useful, and they imply that visual processing should be much slower than it is. Most importantly, they cannot account for recent data showing that some subjects can perform some conjunction searches very efficiently. Feature Integration Theory can be modified so that it accounts for these data and helps to answer these questions. In this new theory, which we call Guided Search, the parallel stage guides the serial stage as it chooses display elements to process. A computer simulation of Guided Search produces the same general patterns as human subjects in a number of different types of visual search. PMID- 2331858 TI - Health-related expenditure patterns in selected migrant groups: data from the Australian Household Expenditure Survey, 1984. AB - Australians born in Italy, Greece and East and South East Asia all have substantially lower mortality levels than those born in Australia, the British Isles or Holland and Germany. Using data from the 1984 Household Expenditure Survey, the health-related consumption expenditure of these six groups was compared (excluding expenditure on medical care). The heterogeneity of household types was largely removed by confining attention to married couple households with dependent children. The two groups with mortality levels comparable to those of the Australian-born (British Isles and Holland/Germany) also shared a similar pattern of consumption expenditures. There was a tendency (not always fully consistent), for the low mortality groups to spend more on fruits, vegetables, cereal products and fish and substantially less on alcohol. Patterns that might be 'unexpected' in low mortality groups are the (presumptively) substantial expenditures on tobacco among males (especially in the Greek group) and the substantial expenditures on red meat in all three groups. Analysis of available data sets such as this can provide useful descriptions of the distribution of health-influencing behaviour in our population. PMID- 2331859 TI - Recent trends and socio-demographic determinants of exercise participation in Australia. AB - Although sentiments about the positive health benefits of regular exercise have been expressed for many centuries, it is only in the past three decades that epidemiologic evidence has provided scientific support for the health benefits of being physically active. The evidence for the protective effect of physical activity is particularly strong with reference to cardiovascular disease, with the relative risk of being "inactive" compared to 'active' estimated to typically lie between 1.5 and 2.0. Despite the popular view that exercise participation has increased in recent years, estimates of trends in physical activity in Australian (and other) populations have been difficult to interpret because of the different measurements and surveys used. We examined data from population surveys using well validated, standardised methods to assess exercise participation, through National surveys between 1984 and 1987 conducted by the Commonwealth Department of the Arts, Sport, the Environment, Tourism and Territories (DASETT). Over the period in which the surveys were conducted, there appears to have been a slight increase in the proportion of Australians who participated in regular physical activity. There was a significant decline in the proportion who reported being totally sedentary--from 32.9 per cent in 1984 to 25.4 per cent in 1987. The data from all of the surveys were then pooled to give an overall sample size of 17053, and socio-demographic variables were examined in relation to exercise participation. Women, older people, the less well educated, and those on lower incomes were less likely to perform regular physical activity. Inequalities in the social distribution of exercise participation parallel those found for other health risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331860 TI - Improving the quality of community health surveys and community health promotion campaigns by feedback from the community: experience from the Wallsend community and health project. AB - A lifestyle and health risk survey was conducted in two socially disadvantaged Collector's Districts, as the basis for a health promotion intervention in one of the Districts. After community input into the planning, and local advance publicity, 395 people responded to the survey (a response rate of 39%). Three sources of community feedback were used: (i) reasons for refusal to participate; (ii) written comments solicited at a two-month follow-up; (iii) later, in-depth interviews with a subset of respondents. The data from this feedback related both to the process and outcomes of the survey; the latter included increased personal and community awareness of health, as well as lifestyle changes. The data are discussed in terms of their representativeness and the factors influencing participation, the implications of the low response rate, the stages of health behaviour change, and the potential conflict between scientific and human value systems in community research. PMID- 2331861 TI - Psychological responses to cancer: a case for cancer support groups. AB - This study investigates the responses of patients and their carers to the diagnosis of cancer. The reporting of stress by patients, using linear analogue scales, and their psychological distress, as measured by the General Health Questionnaire, indicated benefits for members of a community-based cancer support group. The responses of carers revealed that the impact of the diagnosis was as great on them as on patients. Various mediators were considered and age was found to significantly influence the reporting of stress. The limitations and implications of the findings are discussed. PMID- 2331862 TI - Obstetric risks and outcomes: birth centre compared with conventional labour ward. AB - Birth centres in Australia provide an option for women and their professional advisors when choosing the setting for childbirth. It is important that empirical information about the risks is available to enable informed decisions to be made. The purpose of this study was to compare the obstetric outcomes for women admitted to the Birth Centre at Royal Hospital for Women in Sydney with outcomes for women admitted to the conventional labour ward, controlling for prenatal and intrapartum risk. The findings indicate that, with the existing back-up provided by the conventional service, the outcomes for women admitted to the Birth Centre were at least as good as those of the other women. The study also shows that there are differences between the two settings in the management of the intrapartum period. The rate of intervention is substantially higher for women admitted to the Labour Ward, after risk is taken into consideration. The evaluation indicates that the Birth Centre offers a viable choice for women with relatively low obstetric risk. PMID- 2331863 TI - Nursing home admissions: the effect of a multidisciplinary assessment team on the frequency of admission approvals. AB - In a study of nursing home applicants in the Lower North Shore Area of Sydney, the assessed requirement for nursing home care is compared with the Department of Community Services and Health's NH5 approval rate. A multidisciplinary team decided that only 62.6 per cent of 246 nursing home applicants required nursing home admission whereas 98.4 per cent had their applications approved by the Department. The findings suggest that by providing multidisciplinary assessment for nursing home applicants, the previously high approval rates for nursing home admission can be lowered and thus may reduce the number of inappropriate admissions that occur. However, the extent to which this reduction can be maintained will depend on how effective the alternative care options are in preventing or delaying nursing home admission. PMID- 2331864 TI - Accuracy of death certificates and mortality statistics in Victorian testis cancer deaths 1950-1977. AB - 426 death certificates relating to testicular cancer in Victoria, from 1950 to 1977, were examined for inaccuracies in cause of death narrative and coding for cause of death statistics. the narrative was inaccurate in major diagnosis in 33 certificates (21 false positives and 12 false negatives) and 17 accurately written certificates were mis-coded (12 false positives and 5 false negatives). Review of the pathological terms used revealed 10 lymphomas incorrectly ascribed to germ cell malignancy. The term "seminoma" seems to have been employed as a generic term for testis tumour, only 50 per cent of the tumours so designated being confirmed as seminoma. It is concluded that although Victorian figures relating to mortality from testis cancer are reasonably accurate (for 337 cases for which relevant records were available the detection rate was 95%, the confirmation rate 96% and concordance 91%), little reliance can be placed on the recorded pathological sub-type. PMID- 2331865 TI - Preventing human immunodeficiency virus (HIV) infection among prisoners: prisoners' and prison officers' knowledge of HIV and their attitudes to options for prevention. PMID- 2331866 TI - Worksafe Australia: to the McKay report and beyond. AB - The health and safety of workers was not the only raison d'etre for Worksafe Australia. To the Hawke Government, to the ACTU hierarchy and to the employers, a federal initiative in occupational health was a vital item in the ALP-ACTU Accord which would lock the unions into wage restraint. To the already powerful Commonwealth Department of Employment and Industrial Relations the initiative was a golden opportunity to establish a new federal structure under its influence. Thus a bureaucracy, top-heavy with administrators, came into being whilst established national occupational health activities ground to a halt. Plagued by dissent from within and criticism from without, the organisation was saved from extinction only by its importance to the Accord. In 1987 the Government appointed Mr. B. V. McKay to review Worksafe Australia, following which the activities of the organisation were streamlined, with due acknowledgement now given to the key role of the States in giving effect to nationally-agreed policies and standards. However problems remain, and the future of Worksafe Australia is still uncertain. PMID- 2331867 TI - The orifice revisited: women in gynaecological texts. AB - A content analysis was carried out on obstetric and gynaecological textbooks recommended for medical students at four Australian universities. The texts were read for a hidden curriculum of sexist ideology. This study is a partial replication of a study carried out by Scully and Bart in the United States eighteen years ago. The findings of Scully and Bart demonstrated that obstetric and gynaecological texts contained outdated and erroneous views about women's sexuality and portrayed women in stereotyped roles. It was anticipated that institutionalized changes may have occurred since the time that Scully and Bart carried out their research and the texts would reflect this accordingly; particularly with the effect of the women's health movement which has been expressing dissatisfaction with the health care system. The findings of this research show that sexist ideology still pervades the obstetric and gynaecological texts, though to a lesser extent than eighteen years ago. There are some differences from what Scully and Bart discovered, but major similarities were found. The main difference between the results of this study and the findings of Scully and Bart, is that the majority of texts analysed here did not contain outdated and incorrect information about women's sexual response. For example, none of the texts refer to vaginal orgasm as the 'mature' response for women. The main similarity is that women's sexuality is still depicted with a heterosexual perspective, with marriage and mothering the 'natural' aspirations of all women. PMID- 2331869 TI - High activities of cathepsins B, D, H, and L in the white muscle of chum salmon in spawning migration. AB - 1. Activities of cathepsins, lysosomal hydrolytic enzymes and cysteine protease inhibitor in both the white and red muscles of chum salmon (Oncorhynchus keta) caught during spawning and feeding migrations were compared. 2. In the white muscle, cathepsins B, D, H and L activities were 3-7 times higher in the fish in spawning migration than those in feeding migration. However, in the red muscle, no such marked differences were observed between them. 3. Cysteine protease inhibitory activity and extractable protein content in the white muscle of the fish in spawning migration were about 40% lower than those in feeding migration. 4. The present study supports the conception that the cathepsins are related to protein catabolism of the fish during spawning migration. PMID- 2331868 TI - From Medibank to Medicare: trends in Australian medical care costs and use from 1976 to 1986. AB - Private medical care costs and service use in Australia from 1976 to 1986 are compared. In each of these years Australia had a compulsory, universal, fee-for service, national health insurance scheme - Medibank in 1976 and Medicare in 1986. Over the period of 1976 to 1986, the number of private medical services per capita, in the 6 month period 1 April to 30 September, increased from 2.79 to 3.95, an increase of 3.54 per cent per year. The cost of services per capita, adjusted for increases in schedule fees for each item-group of services (the 'fee adjusted cost'), grew at a rate of 3.91 per cent per year. The results are reported by subsets of age, sex and item-group of service. It is found that very little of the large increases in use and cost of services can be attributed to demographic changes or population growth. Rather, they represent rapid increases in age and sex-specific rates of use, primarily among the very young, the very old and, for some types of service, women of child-bearing age. The most dramatic increases in service use are found in pathology, radiotherapy and miscellaneous procedures. PMID- 2331870 TI - Purification and characterization of uracil phosphoribosyltransferase from Crithidia luciliae. AB - 1. Uracil phosphoribosyltransferase (UPRTase) was purified 370-fold from the protozoan parasite, Crithidia luciliae. 2. The enzyme was a dimer of mol. wt 80 000 and was highly specific for uracil. 3. GTP, which is an activator of UPRTase from E. coli had a slight inhibitory effect on the parasite enzyme. 4. The C. luciliae UPRTase demonstrated a broad specificity for activating divalent metal ions. PMID- 2331871 TI - A heat-stable alkaline phosphatase from Penaeus japonicus Bate (Crustacea: Decapoda): a phosphatidylinositol-glycan anchored membrane protein. AB - 1. A heat-stable alkaline phosphatase was purified from Penaeus japonicus, with a final specific activity of 21,280 U/mg of protein. 2. In polyacrylamide-gel electrophoresis under non-denaturing conditions, the purified shrimp alkaline phosphatase was found to have an identical molecular size and surface charge as the human placental enzyme. 3. By using SDS-PAGE, the monomers of shrimp alkaline phosphatase were discovered to have a Mr 55,000 but those of human placental enzyme with a Mr 70,000. Deglycosylation decreases the Mr values of the subunits to 33,000 for shrimp alkaline phosphatase. 4. The purified alkaline phosphatase from shrimp was recovered with both the attachment sites for sialic acids and phosphatidylinositol. 5. The shrimp alkaline phosphatase has an isoelectric point (pI) of 7.6 and the human placental enzyme has a pI of 4.8. PMID- 2331872 TI - Lipids of Angiostrongylus cantonensis (Nematoda: Metastrongyloidea): a comparison between young adults and gravid worms. AB - 1. All major classes of lipids were found in the young adults in brain (22 days post-infection) and gravid Angiostrongylus cantonensis in lung of rats (34 days post-infection) comprising approximately 60% of phospholipids, 30% of neutral lipids and the rest, glycolipids. 2. The relative composition of phospholipids were quite similar between worms from the two different habitats, with phosphatidylcholine predominating. The glycolipid profiles were also similar. 3. More neutral lipids in the worms from brain existed as cholesterol and cholesterol esters than those from the lung. More than 20% of the fatty acids in these lipids of the brain were found as C10-C14 acids while oleic acid was the main component in the lung worm. PMID- 2331873 TI - Sialic acid and neuraminidase activity in the frog oviduct: comparative biochemical investigation in the different tracts during the reproductive cycle. AB - 1. A biochemical study was carried out on the protein-bound and lipid-bound sialic acid, and neuraminidase activity in the different tracts of the oviduct of the frog Rana esculenta during the reproductive cycle. 2. Plasma sexual steroids were also investigated by RIA. 3. Fluctuations in neuraminidase activity are related to that of glycoprotein sialic acid and plasma estradiol. Glycolipid sialic acid does not have a close relationship either with neuraminidase or plasma estradiol. 4. Very high plasma concentration of progesterone before ovulation and, on the contrary, its drop after ovulation were observed. 5. The results are discussed and hypotheses advanced to explain fluctuations of the studied parameters during the reproductive cycle. PMID- 2331874 TI - Antibacterial activity of Eisenia fetida andrei coelomic fluid: transcription and translation regulation of lysozyme and proteins evidenced after bacterial infestation. AB - 1. After bacterial infestation lysozyme and antibacterial activities are enhanced, peaking at 4 hr and 3 days, respectively. 2. Both humoral defenses require RNA and protein de novo synthesis in response to pathogenic bacteria injection (actinomycin D and cycloheximide experiments). 3. Antibacterial activity exists naturally at some basic level, involving regular translation of stable RNAs. 4. When antibacterial activity reaches its maximum after bacterial injection, proteins responsible for it undergo a turn-over. 5. Lysozyme and antibacterial proteins cannot account for the whole response to bacterial infestation; some cellular defense mechanisms like phagocytosis are involved at the same time. PMID- 2331875 TI - Comparative studies of catalase and superoxide dismutase activity within salmon fish erythrocytes. AB - 1. Superoxide dismutase isolated from erythrocytes of several species of salmon and the rainbow trout exhibited single electrophoretic bands of activity which migrated anodally similar to the human erythrocyte enzyme; two discrete bands were observed for the coho salmon. 2. No polymorphism was observed for 30 samples from sockeye salmon and six samples from king salmon. Only one sample of rainbow trout (one of 12) exhibited an electrophoretic mobility difference. 3. Catalase migration on starch-gel resembled the human enzyme's electrophoretic mobility for all salmon species and rainbow trout. Catalase activity of the sockeye salmon (2929 +/- 895 mumol min-1 gHb-1) was determined to be lower than human catalase activity. 4. All samples differed from the human enzymes in that they required the presence of a detergent, Triton X-100, for solubilization. PMID- 2331876 TI - Comparative studies on lipogenic enzyme activities in the liver of human and some animal species. AB - 1. The activities of enzymes involved in fatty acid synthesis in the human liver (sample taken during abdominal surgery) and in the livers of some animals were studied. 2. Fatty acid synthase, ATP-citrate lyase and malic enzyme activities were found to be from 4 to 70-fold lower in human liver than in rat or bird livers. 3. The activities of hexose monophosphate shunt dehydrogenases in human liver were from half to almost equal to the corresponding activities in birds, but much lower than in rat liver. 4. The activities of all enzymes listed above in human and beef liver were very similar (except fatty acid synthase which was undetectable in the beef liver). 5. Very high activity of NADP-linked isocitrate dehydrogenase was found in livers of all species tested. 6. These results are discussed in relation to the role of the human liver in lipogenesis. 7. The activities of the enzymes generating NADPH in human liver taken during abdominal surgery were similar to the activities observed in the tissue obtained post mortem. 8. This suggested that post mortem tissue may be used as a reliable human material for some enzyme assays. 9. Thus we also examined the activity of malic enzyme in post mortem human kidney cortex, heart, skeletal muscle and brain. 10. Relatively high activity of NADP-linked malic enzyme has been observed in human brain. PMID- 2331877 TI - Partial purification and characterization of cysteine proteinases from various developmental stages of Paragonimus westermani. AB - 1. During development of Paragonimus westermani, larvae develop during migration within the host, and adult worms feed on pulmonary tissues, causing significant pathology in the mammalian host. In this report acidic extracts of various developmental stages (metacercariae and worms at one, two and three months of development) were examined for cysteine proteinase activity. 2. A soluble thiol dependent proteinase activity with a native molecular weight of approximately 20,000 was isolated and partially purified. 3. The enzymes purified from the various developmental stages of the parasite had maximal activity at acidic pH and showed inhibitor susceptibilities similar to the vertebrate acidic cysteine proteinases. 4. Enzymatic activity was stable at pH 5.0 for at least two days when stored at 4 degrees C. 5. It is suggested that these enzymes may be involved in the nutrition of these parasites and/or during penetration and lysis of the tissues. PMID- 2331878 TI - A comparative study of superoxide dismutase in various animal species. AB - 1. Superoxide dismutase activity has been determined in liver homogenates of five species. There were no significant differences in the activities of the enzyme in the rat, rainbow lizard, wall gecko and chicken. The activity was significantly lower in the fish. 2. The order of activity of the enzyme in the organs/tissues of the rat was liver greater than kidney greater than heart greater than skeletal muscle greater than brain greater than lung greater than spleen greater than spinal cord greater than retina greater than pancrease greater than lens greater than small intestine. 3. Inhibition studies with cyanide showed that the enzyme in the liver of the various animal species was inhibited by cyanide. 4. The developmental pattern for the enzyme showed no significant changes in the liver of the rat from birth and up to 7 weeks after. However, the activity increased at about 8 weeks and remained constant to adult life. PMID- 2331879 TI - Brain synaptosomal Ca2+ uptake: comparison of Sprague-Dawley, Wistar-Kyoto and spontaneously hypertensive rats. AB - 1. K(+)-stimulated 45Ca2+ uptake by synaptosomes was measured with respect to the strain differences between Sprague-Dawley (SD), Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. 45Ca2+ uptake by synaptosomes isolated from cerebral cortex of SD, WKY and SHR was measured at 15, 30, 60, 120 and 240 sec time periods. 3. The sequence of both the magnitude and rate of resting and depolarization-dependent 45Ca2+ uptake was SHR greater than WKY greater than SD. 4. The fastest rates of resting and depolarization-dependent 45Ca2+ uptake occurred in each rat during the first 15 sec and uptake rates dropped off quickly in both resting and depolarization states. 5. At 15 sec, there were significant differences between SHR and WKY, while there were no significant differences between WKY and SD. 6. The results suggest that an important alteration in Ca2+ channel characteristics may occur in SHR brain synaptosomes. PMID- 2331880 TI - Purification and properties of glutamyl aminopeptidase from chicken egg-white. AB - Hydrolytic activities characteristic for different aminopeptidases were detected in the egg-white of unfertilized chicken eggs, and one aminopeptidase was isolated in an electrophoretically homogeneous form. The isolated aminopeptidase preferentially hydrolyzed bonds of alpha-glutamyl residue at the NH(2)-end of synthetic substrates and peptides. The enzyme is a dimer with an M(r) of 320,000 and pI of 4.2. Its optimal pH and temperature are 7.6 and 60 degrees C, respectively. EDTA, amastatin, and N-bromosuccinimide are inhibitors, while Ca2++ and Mn2+ are activators of the enzyme Ca2+ also stabilizes the enzyme. According to the observed properties, the isolated chicken egg-white aminopeptidase belongs to the glutamyl aminopeptidases. PMID- 2331881 TI - Immunological distinction between piscine and mammalian metallothioneins. AB - 1. Separate antisera to metallothioneins (MT) from rainbow trout and horse were produced in mice and their reactivity with the respective immunogen was confirmed using an ELISA. 2. The ELISA, used in a competitive mode, revealed that the anti horse MT serum did not cross-react with trout MT. Reciprocally, the anti-trout MT serum did not show any reactivity with horse MT. 3. The anti-rainbow trout MT serum was shown to cross-react totally with MTs from plaice, flounder, turbot, perch, salmon and pike, but exhibited no reactivity towards MTs from human, mouse, rat, worm or crab. Partial reactivity with the proteins isolated from oyster and mussel was demonstrated. 4. The anti-horse MT serum cross-reacted totally with MTs from human, rat and rabbit but no reactivity was demonstrable when MT from either plaice or worm was tested. 5. The behaviour of apo-, holo- and recombinant rainbow trout MTs, in which the metal content was different, indicated that reactivity with anti-MT antibodies was not dependent on the presence or nature of the metals bound in the protein. 6. The patterns of reactivities were analysed in relation to the known amino acid sequences of MT. PMID- 2331882 TI - Isolation and purification of glutathione S-transferases from Brachionus plicatilis and B. calyciflorus (Rotifera). AB - 1. The enzyme glutathione S-transferase (GST), a critical element in xenobiotic metabolism, was isolated from the marine rotifer Brachionus plicatilis and its freshwater congener B. calyciflorus. 2. In B. plicatilis, GST comprised 4.2% of cytosolic protein and was present as three separate isozymes with mol. wts 30,000, 31,400 and 33,700. Specific activity of crude homogenates was 56 nmol min 1 mg-1 protein, while that of affinity chromatography purified GST was 1850. 3. In B. calyciflorus, GST was present as two isozymes with mol. wts of 26,300 and 28,500, representing 1.0% of cytosolic protein. Crude GST specific activity was 1750 nmol min-1 mg-1 protein and purified was 72,400. 4. Rotifer GSTs are unusual because they are monomers whereas all other animals thus far investigated posses dimeric GSTs. PMID- 2331883 TI - Evidence for tight coupling of phospholipase activation and Ca2+ influx during acrosome reaction of golden hamster spermatozoa. AB - 1. Phospholipases have been proposed to play a key role in sperm acrosome reaction. To examine the activation mechanism of phospholipases and subsequently sperm fertilizing capacity. Ca2+ fluxes and phospholipid turnover (breakdown and synthesis) were investigated in golden hamster spermatozoa during acrosome reaction. 2. Upon exposure of the spermatozoa to 1.7 mM Ca2+, a net uptake by the cells occurred in two distinguishable phases. 3. Depletion of extracellular Ca2+ by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) at a time that an initial Ca2+ uptake was observed to reach almost steady-state, prevented the secondary Ca2+ uptake and acrosome reaction. 4. The time course of an initial Ca2+ uptake seemed to precede that of the acrosome reaction. 5. Incubation of the spermatozoa with Ca2+ in the presence of [3H]glycerol induced a rapid increase in labeling of phosphatidic acid, a key intermediate of phosphinositide turnover initiated by the action of phospholipase C, which appeared to parallel the time course of a first phase of Ca2+. 6. Phospholipase A2 activation, detected by lysophospholipid formation, slightly delayed the initial events of first Ca2+ uptake and phosphatidic acid production. 7. It is concluded that first Ca2+ entry into the cells, associated with phosphatidic acid production, activates a phospholipase A2, leading to the production of substances, like lysophospholipids and fatty acids, which may contribute to acrosome reaction. PMID- 2331884 TI - Cryopreserved autologous bone marrow transplantation in patients with acute nonlymphoid leukemia: chemotherapy before harvesting is the main factor in delaying hematological recovery. AB - We analyzed the kinetics of hematological recovery after autologous bone marrow transplantation in 13 patients with acute nonlymphoid leukemias (ANLL). A comparison was made with 31 patients with non-Hodgkin's lymphoma (NHL) whose bone marrow was harvested and cryopreserved, either at diagnosis or after intensive chemotherapy. Hematological recovery of ANLL patients was similar to that of pretreated NHL patients and significantly slower than that of untreated NHL patients. We suggest that chemotherapy before harvest (more than the possible decreased stem cell marrow potentiality resulting from the underlying disease) appears to be the main factor responsible for delayed recovery after autologous bone marrow transplantation in ANLL. PMID- 2331885 TI - Permeation of glycerol and propane-1,2-diol into human platelets. AB - The permeability of human platelets to glycerol (GLY) and propane-1,2-diol (propylene glycol, PG) has been determined by measuring the time course of their change in volume following abrupt immersion in solutions of these solutes. A simple light-scattering method, and its calibration to measure mean platelet volume is described. The data are analyzed by means of the Kedem-Katchalsky (K-K) equations, modified to take into account the nonideal behavior of both intracellular and extracellular solutes. The values of the K-K parameters at 2, 21, and 37 degrees C, respectively, were as follows: the hydraulic conductivities (Lp) were 1 x 10(-7), 7 x 10(-7) and 3 x 10(-6) cm.sec-1.atm-1; the solute permeabilities for PG (omega RTPG) were 1.9 x 10(-6), 2.8 x 10(-5), and 1.3 x 10( 4) cm.sec-1; the solute permeabilities for GLY (omega RTGLY), at 21 and 37 degrees C only, were 2.6 x 10(-7) and 1.4 x 10(-6) cm.sec-1. The reflection coefficient (sigma) was 1 throughout. The relevant activation energies were -Lp, 16.5 kcal.mol-1; omega RTPG, 20.5 kcal.mol-1; and omega RTGLY, 17.9 kcal.mol-1. The use of these data is illustrated by computing schedules for the addition and removal of GLY and PG so that the amplitudes of changes in platelet volume are held within predetermined limits. PMID- 2331886 TI - Some effects of propane-1,2-diol on human platelets. AB - The Kedem-Katchalsky equations and permeability data previously reported (F. G. Arnaud and D. E. Pegg. Permeation of glycerol and propane-1,2-diol into human platelets. Cryobiology 27, 130-136, 1990) have been used to design methods for adding and removing propane-1,2-diol (propylene glycol, PG) with human platelets. Mean platelet volume was kept within the tolerated range of 60 to 120% of normal. PG concentrations of 0.5, 1.0, 2.0, 2.5, and 3.0 M were studied at 2, 21, and 37 degrees C. PG was removed only at 21 degrees C. The effects of concentration of PG, temperature, and duration of exposure on the hypotonic stress response and ADP-induced aggregation were measured. It was found that platelets would tolerate exposure to PG concentrations up to 2 M at 21 or 2 degrees C for up to 15 min. The extent of damage increased considerably at higher temperatures and concentrations. These data provide the necessary basis for experiments to cryopreserve platelets with PG. PMID- 2331887 TI - Cryopreservation of human platelets with propane-1,2-diol. AB - The preceding papers in this series have described techniques that permit the introduction and removal of propane-1,2-diol (propylene glycol, PG) with human platelets, in concentrations up to 2 M, without producing serious damage. These methods have now been used in attempts to cryopreserve platelets, with assessment of survival by the hypotonic stress response and ADP-induced aggregation. PG concentrations of 0.5, 1.0, 2.0, and 2.5 M and cooling rates between 0.4 and 100 degrees C/min were studied. The maximum response in the hypotonic stress test was no better than 17% and the greatest ADP-induced aggregation was only 6%; these results were obtained with 0.5 M PG, a cooling rate of 14 degrees C/min, and rapid warming (approximately 150 degrees C/min). The failure of PG concentrations greater than 0.5 M to improve survival was unexpected. When cooling was interrupted at progressively lower temperatures and function assessed, it was possible to relate the extent of damage to temperature and then, with the aid of phase diagrams, it was possible to show that, irrespective of the initial concentration of PG, the extent of damage was closely correlated with the concentration of PG produced at the minimum temperature used. It is concluded that the toxicity of PG increases so steeply with the increasing concentration produced by the separation of ice during freezing that this effect is sufficient to counteract the cryoprotective action of this solute for platelets. PMID- 2331888 TI - Hair follicle destruction and regeneration in guinea pig skin after cutaneous freeze injury. AB - We have investigated the histological changes in hair follicles in guinea pig skin after standardized moderate and severe cryosurgery injuries. Hair follicles were permanently destroyed by cryosurgery, but more than one mechanism may be operative during follicle destruction and shedding. The mechanism depends upon the severity of the freeze. After a light freeze injury, the changes are predominantly within the hair follicle. The hair is shed at the surface and there is selective autolysis of follicular cells, but dermal connective tissue is preserved and there is little surrounding damage. However, after a severe cryoinjury as used in "tumor doses," there is destruction of dermal connective tissue and dermal scarring. The necrotic dermis is shed, taking with it the dead follicles and morphologically normal elastic tissue. PMID- 2331889 TI - Effects of cryobiological variables on the survival of skin using a defined murine model. AB - Skin from an inbred strain of hairless mouse was used as a homogeneous model tissue for studies of skin cryopreservation. Tetrazolium reductase enzyme activity was used to assess tissue viability. Hepes-buffered 199 tissue culture medium was confirmed to be a suitable basal medium, to which cryoprotectants were added. Addition of serum to the cryoprotective cocktail had no beneficial effect. Three cryoprotectants, dimethyl sulfoxide, ethanediol, and glycerol were evaluated. There was no evidence of specific toxicity attributable to the cryoprotective agents during the permeation period; however, short permeation times at low temperature were associated with maximum skin viability. Following freezing and thawing, higher viabilities were obtained when using a slow (-1 degree C min-1) or medium (-60 degree C min-1) rather than a fast (immersion in liquid nitrogen) cooling rate. Dimethyl sulfoxide was a marginally better cryoprotectant overall, although this difference was not statistically significant. PMID- 2331890 TI - Cold-induced ultrastructural changes in bull and boar sperm plasma membranes. AB - The effect of low temperatures on the ultrastructure of the plasma membrane of bull and boar spermatozoa was investigated. Cold-induced changes in the organization of sperm plasma membrane components were demonstrated by the use of fast-freezing combined with freeze-fracture electron microscopy. This preparation technique ensures fixation without artifacts. At 38 degrees C bull and boar spermatozoa exhibited a random distribution of intramembranous particles over the plasma membrane of both head and tail. Exposure to 0 degree C resulted in redistribution of the intramembranous particles: on the head and principal piece of bull spermatozoa and on the principal piece of boar spermatozoa, particle-free areas were observed, whereas on the boar sperm head, particle aggregates were present. The original particle distribution was restored upon rewarming of bull and boar spermatozoa to 38 degrees C, as well as after freezing and thawing of bull spermatozoa. Dilution of bull and boar semen into Tris-dilution buffer and Beltsville Thaw Solution-dilution buffer, respectively, could not prevent cold induced redistribution of intramembranous particles. The observed particle reorganization upon cooling was interpreted as the result of lateral phase separation in the plasma membrane. Species-dependent differences in cold-induced ultrastructural changes were considered to be determined by lipid composition and asymmetry of the plasma membrane, and might be related to differences in cold resistance between species. PMID- 2331891 TI - Experimental frostbite: freezing times, rewarming times, and lowest temperatures of pig skin exposed to chilled air. AB - Frostbite was produced in the skin of five Hanford Miniature Swine by exposing local areas to chilled air (-75 degrees C) for 1, 3, 5, 10, or 20 min. A copper constantan thermocouple was inserted into the dermis to measure the temperature. The mean freezing time (the time required to reach 0 degrees C) was approximately 1.9 min. The mean lowest temperatures were 8.8, -15.7, -20.9, -22.5, and -23.4 degrees C for the 1-, 3-, 5-, 10-, and 20-min freezes, respectively. The mean times to rewarm the skin to 25 degrees C were 3.1, 4.5, 5.5, 7.0, and 8.6 min for the 1-, 3-, 5-, 10-, and 20-min freezes, respectively. Significant linear correlations existed between duration of freeze and rewarming times, duration of freeze and lowest temperature, and lowest temperature and rewarming times. PMID- 2331892 TI - Morphometric analysis of human chromosome satellites and NOR asymmetries by transmission electron microscopy. AB - Human chromosome satellites appear as roughly spherical telomeric structures of 0.215 +/- 0.013 microns mean diameter by electron microscopy. Morphometric evaluations showed that in the short arms of D and G chromosomes lacking secondary constrictions, the chromatin which constituted the satellites appeared virtually integrated within the short arms. Asymmetry was detected in sister satellites from almost identical dimensions to the near absence of one of them. When Ag-NOR staining was employed to locate active nucleolar organizer regions (NORs) these appeared associated with satellite short arms and active NORs were never found in non-satellite chromosomes. Asymmetry was also evident between sister NORs. PMID- 2331893 TI - ARDS: the therapeutic dilemma. PMID- 2331894 TI - Ventilator-associated pneumonia. Light at the end of the tunnel? PMID- 2331895 TI - Toward smoke-free medical facilities. PMID- 2331896 TI - As the liver goes, so goes the lung. PMID- 2331897 TI - Adiaspiromycosis. An uncommon disease caused by an unusual pathogen. PMID- 2331898 TI - Pulmonary disease associated with L-tryptophan-induced eosinophilic myalgia syndrome. Clinical and pathologic features. AB - Tablets and capsules containing the essential amino acid L-tryptophan are currently being investigated as a cause of the newly recognized eosinophilia/myalgia syndrome. In the five histologically documented cases reported herein, L-tryptophan ingestion was associated with prominent pulmonary complications. All patients were women ranging from 34 to 65 years, and all presented with respiratory symptoms that began after one to nine months of L tryptophan therapy. Peripheral eosinophilia was present in four patients as were bilateral interstitial infiltrates on chest roentgenograms. One patient had a normal chest roentgenogram. Lung biopsies were done in all patients and biopsy specimens showed a vasculitis and perivasculitis associated with a mild chronic interstitial pneumonitis and eosinophilia. Three patients had clinical and/or histologic evidence of pulmonary hypertension, and one had a follicular bronchiolitis. Four patients recovered promptly with steroid therapy and discontinuation of L-tryptophan therapy, and one patient has had minimal symptomatic improvement. PMID- 2331899 TI - Mediastinal spread of metastatic lymph nodes in bronchogenic carcinoma. Mediastinal nodal metastases in lung cancer. AB - The location, frequency, and spread of metastases to the mediastinal lymph nodes were examined in 124 patients with histologically proven N2 disease who underwent pulmonary resection and total lymph node resection. There were one-level metastases in 47 percent of cases, two-level metastases in 29 percent, three level in 12 percent, and 12 percent had four or more levels of metastases. Nodal metastases to the lower mediastinum from upper lobe cancer were frequently observed as were metastases of lower lobe cancer to the upper mediastinum. The frequency of the latter was higher than that of the former. About one third of squamous cell carcinoma and adenocarcinoma in the right upper lobe produced nodal metastases in the lower mediastinum. In addition, there were often skip metastases to the nonregional parts of the mediastinum without regional nodal involvement in the mediastinum. From the results of the present study, it appears that extensive mediastinal dissection should be recommended in surgery for lung cancer irrespective of the location of the primary tumor. PMID- 2331900 TI - Bronchoalveolar lavage findings in patients seropositive for the human immunodeficiency virus (HIV). AB - To evaluate bronchoalveolar lavage (BAL) findings in patients infected with human immunodeficiency virus (HIV), 39 patients seropositive for the virus but with no history of opportunistic infection were studied. Opportunistic organisms such as Pneumocystis carinii were not found in any of the 35 BAL fluids sent for special stains and cultures. Three of 16 (18 percent) BAL fluids sent for HIV culture were positive compared with a 60.9 percent blood HIV culture positivity in the same group. To evaluate cellular recovery, the patients were divided into Walter Reed (WR) groups 1 and 2 (blood CD4 greater than or equal to 400/cu mm) and WR3 to WR5 (blood CD4 less than 400/cu mm). Compared with ten nonsmoking healthy controls, the WR1 and WR2 group had a greater overall cellular recovery but this was not statistically significant when the smokers were excluded. There was no difference in macrophage or lymphocyte percentages in either patient group compared with controls. T-cell subset analysis of a small group of WR1 to WR5 patient BAL fluids revealed no difference in CD4 numbers or the CD4/CD8 rate between WR1 and WR2 and WR3 to WR5 patients. We conclude that opportunistic pulmonary infection is unlikely in HIV-seropositive patients with normal chest roentgenograms despite symptoms of dyspnea on exertion. Also, HIV can be isolated from BAL fluid from these patients although not as often as from blood. Finally, there appears to be no distinct progression in BAL cellular findings before the onset of acquired immunodeficiency syndrome. PMID- 2331901 TI - Quantifying ventilatory reserve to predict respiratory failure in exacerbations of COPD. AB - We developed a concept of VR in patients with acute exacerbation of advanced COPD and tested the hypothesis that it is predictable and clinically useful in the ER. Our concept of VR was based on the idea that a threshold VF and a MSV capacity are measurable; ie, VR = MSV - VF. We measured resting minute ventilation, the 15 s MVV, FEV1 and ABG values in 13 patients with exacerbation of COPD in the ER and 11 stable subjects with similar degrees of COPD. We tested if measures of VR could distinguish between ER patients progressing to respiratory failure, ER patients who avoided progression to respiratory failure and stable patients. There were significant differences in measures of the mean VR between various groups of patients. We conclude that in this COPD population, VR can be accurately predicted in the ER and that it may be a clinically valid predictor of patient outcomes. PMID- 2331902 TI - Cardiac arrhythmias and left ventricular function in respiratory failure from chronic obstructive pulmonary disease. AB - In 22 patients with COPD, we studied the relationship between left ventricular function and cardiac arrhythmias. Ventricular arrhythmias were detected on a 24-h ECG recorded at the beginning of the observation period and after a stable improvement of RF. Left ventricular function was evaluated by equilibrium-gated radionuclide angiocardiography measuring LVEF, PER and PFR. We found a significant decrease in the arrhythmia score after improvement of RF; LVEF and PFR were slightly depressed in six and nine patients, respectively. A "step-up" multiple regression analysis revealed a significant inverse correlation between PFR and ventricular arrhythmias during worsened RF, whereas LVEF, arterial blood gases and clinical data were not significantly predictive variables. Thus, a depressed left ventricular diastolic performance seems to be a predictive factor for arrhythmias during RF from COPD. The poor definition of the statistical model suggests that other presently unknown factors contribute to the genesis of ventricular arrhythmias. PMID- 2331903 TI - Platelet and plasma catecholamines in relation to plasma minerals and parathyroid hormone following acute myocardial infarction. AB - Epinephrine has been shown to lower the plasma concentrations of several minerals and elevate those of parathyroid hormone (PTH). In order to evaluate the possible clinical importance of such experimental observations, 34 patients with acute myocardial infarction (AMI) were studied with daily determinations of plasma catecholamines, minerals, and PTH during the first week after AMI and at follow up one month later. In addition, platelet catecholamines were determined as they fluctuate more slowly than plasma catecholamines. After infarction initial platelet epinephrine and norepinephrine levels were higher (p less than 0.05 for both) in nonsurvivors than survivors during a one year follow-up. Results suggested that activation of the sympathoadrenal system influences calcium homeostasis following AMI, but that the impact of sympathoadrenal activation on mineral metabolism is of minor clinical significance in the average AMI patient. High platelet catecholamine levels may predict a poor outcome after AMI. PMID- 2331904 TI - Short-term control of supraventricular tachycardia with verapamil infusion and calcium pretreatment. AB - Nineteen consecutive patients with atrial fibrillation/flutter or other types of supraventricular tachycardia were given intravenous (IV) calcium salts (1 g) followed by verapamil infusion at a rate of 1 mg/min. Successful treatment was defined as control of ventricular response to less than or equal to 100 beats per minute (bpm) or conversion to sinus mechanism in patients with atrial arrhythmias: 11 patients had atrial fibrillation; three had atrial flutter; four had reentrant supraventricular tachycardias (SVT); and one had paroxysmal SVT. Therapy was successful in all patients. The mean dose of verapamil required to achieve desired outcome was 20 mg. Heart rate showed no significant change as a result of calcium pretreatment (160 bpm v 151 bpm). However, heart rate was significantly decreased, to 95 bpm, after treatment with verapamil. Blood pressure showed no change from baseline with either calcium or verapamil therapy. Verapamil infusion following IV calcium successfully treats atrial fibrillation/flutter or SVTs without depressing systemic blood pressure. PMID- 2331905 TI - Diaphragmatic breathing maneuvers and movement of the diaphragm after cholecystectomy. AB - Coached efforts at diaphragmatic breathing were assessed as a means of increasing diaphragmatic movement in postoperative patients. Inductive plethysmography was used to measure compartmental tidal volumes of the abdomen (Vab) and the chest (Vc) in eight women (aged 41 +/- 16 years) who had no history of cardiovascular or pulmonary disease. These patients were studied before and after (POD1,3) elective cholecystectomy. In preoperative studies, DB increased the supine value of Vab. The corresponding increase on POD1 represents a similar proportion of the resting value. The postoperative fall in resting and stimulated values of Vab is attributed to the known effects of abdominal surgery on diaphragmatic movement. Hence, DB warrants investigation as a method of prophylaxis against the pulmonary complications of surgery, because diaphragmatic movement is largely responsible for ventilation of the lower lung fields, where atelectasis and infection occur most often. PMID- 2331906 TI - Respiratory tract deposition of ultrafine particles in subjects with obstructive or restrictive lung disease. AB - To evaluate the effects of lung disease on deposition of inhaled ultrafine particles (less than 0.1 micron diameter), we measured total respiratory tract deposition of nonhygroscopic particles of 0.02 to 0.24 micron in five subjects with obstructive lung disease and three subjects with restrictive lung disease and compared it with that in ten normal subjects. Deposition was measured as concentration difference of five size fractions in inhaled and exhaled air using an electrical aerosol analyzer. The data showed that deposition of these ultrafine particles was increased in subjects with obstructive lung disease when compared with normal subjects, while it was unchanged in subjects with restrictive lung disease. The increase in deposition in the subjects with obstructive lung disease was significant for particle sizes 0.04 to 0.24 micron. Possible mechanisms for increased deposition in airway obstruction include increased transit time of particles, abnormal expiratory collapse of airways due to flow limitation, and flow perturbations resulting from decreased airway caliber. PMID- 2331907 TI - Effect of cardiac output on gas exchange in one-lung atelectasis. AB - To evaluate the effect of administration of dobutamine on gas exchange in patients with one-lung atelectasis during pneumonectomy, ten patients with normal pulmonary function and localized carcinoma of the lung were studied during pulmonary resection. With each patient in the lateral decubitus position, hemodynamic profiles and oxygen transport data were recorded before and after administration of dobutamine at 5 micrograms/kg/min. Patients were ventilated with one-lung anesthesia and administration of 100 percent oxygen. With infusion of dobutamine, the heart rate, cardiac index, and LVSWI significantly increased. Mean arterial pressure increased while PAP fell. Systemic and pulmonary vascular resistance also declined. Arterial oxygenization and delivery improved, while oxygen uptake was unchanged. Pulmonary shunt fraction was significantly reduced. While the mechanism for shunt reduction in our patients is unclear, operative factors may include pulmonary vasodilation with dobutamine inhibition of HPV. The negative impact of reduced HPV may have been lessened by gravitational distribution of blood flow and dobutamine-mediated reduction in PAP in our patients. PMID- 2331908 TI - Risk assessment in urgent/emergent coronary artery surgery. AB - A statistical model has been developed to allow for prediction of individual patient prognosis following urgent/emergent coronary artery bypass grafting (CABG). None of the models previously described for use in coronary artery surgery has been tested with a prospective patient series that confirms the true predictive capacity of the model. Ideally, the predictive ability of such models should be validated with prospective trials. To examine the feasibility of statistical modeling in this clinical context, a computerized model based on the theorem of Bayes was developed to predict operative mortality for urgent coronary artery surgery. The presence or absence of 20 risk factors was determined for each of 405 consecutive patients undergoing urgent coronary artery surgery from January 1984 to January 1989. The first 100 patients were used to develop a database for the model, which was then used to prospectively evaluate the remaining 305 patients. There was good agreement between predicted and observed results. Models of this kind are particularly advantageous because of the ability to (1) accommodate multiple risk factors, (2) become tailored to a specific practice, and (3) determine individual rather than group prognosis. Validation with a prospective trial confirms the practical utility of this approach. This model has reliably predicted the risk associated with urgent coronary artery surgery and may provide important clinical information for the management of patients being evaluated for urgent revascularization. PMID- 2331909 TI - Cardiopulmonary exercise testing after single and double lung transplantation. AB - The cardiopulmonary response to exercise was investigated in six single and six double lung transplant recipients using a three-minute incremental work rate protocol on a cycle ergometer. Maximum VO2 averaged 44.2 +/- 9.2 percent and 48.5 +/- 5.0 percent of predicted maximal VO2 in the single and double lung transplant groups, respectively. No evidence of ventilatory limitation to exercise was found in either group. Circulatory factors that may have limited exercise capacity included anemia and submaximal heart rates. There was a strong correlation between VO2/kg at venous blood lactate level of 2.2 mEq/L and vital capacity/body surface area in the single, but not in the double, lung recipients. Maximum VO2 in these lung transplant recipients was comparable to previously published values in heart-lung transplant recipients. The factors that limit maximum exercise capacity after lung transplantation deserve further study. PMID- 2331910 TI - Elevated levels of soluble interleukin-2 receptors in tuberculous pleural effusions. AB - The levels of soluble IL-2R were measured in pleural fluid from patients with tuberculosis pleurisy. There were significantly elevated soluble IL-2R values in tuberculous pleural fluid as compared with pleural fluid of nontuberculous etiology including malignant, bacterial and transudative pleural effusions. In patients with tuberculous pleurisy, the level of soluble IL-2R in pleural fluid was markedly greater than that in serum. Furthermore, a significant positive correlation was observed between soluble IL-2R levels and adenosine deaminase levels in tuberculous pleural fluid. These findings suggest that elevated levels of pleural fluid soluble IL-2R in tuberculous pleurisy could reflect the local proliferation of activated T-cells and may be clinically useful in the diagnostic procedures for patients with pleural tuberculosis. PMID- 2331911 TI - Measurement of functional residual capacity during high-frequency oscillatory ventilation (HFOV) by argon washout method without interruption of HFOV. AB - A modified indicator gas washout method was developed to measure functional residual capacity (FRC) during high-frequency oscillatory ventilation (HFOV) without interruption of HFOV. A hot-wire flowmeter and medical gas analyzer measured the flow rate and argon concentration, respectively, at the expiratory end of the respiratory circuit. Upstream of the hot-wire flowmeter, two heat-and moisture exchangers for resistance and a rubber balloon for capacitance were placed to convert the oscillating expiratory flow to an almost continuous flow. This made it possible to measure FRC during HFOV without interrupting HFOV. To measure the volume of the entire respiratory circuit, a 10 percent argon in 90 percent oxygen gas mixture was initially used as a bias flow, and after equilibration, the test gas was switched to 100 percent oxygen. By electrical integration of the product of the expiratory flow rate and argon concentration, the total amount of argon equilibrated in the entire respiratory circuit was calculated. The volume of the circuit was calculated by dividing the total amount of argon by the initial argon concentration. Functional residual capacity plus the volume of the respiratory circuit was similarly calculated and the difference was estimated as FRC. The accuracy and reproducibility of our method were evaluated by using a one-compartment lung model. There was a high correlation between the volume setting of the model lung and the estimated FRC. This method can be used to estimate FRC in a one-compartment lung model during HFOV, and it is potentially useful in clinical situations. PMID- 2331912 TI - Respiratory mechanics in anesthetized young patients with kyphoscoliosis. Immediate and delayed effects of corrective spinal surgery. AB - To our knowledge, the effects of corrective spinal surgery on total respiratory mechanics and its components in anesthetized patients with kyphoscoliosis have not been previously reported in detail. We studied 13 patients with kyposcoliosis; their mean (+/- SD) age was 24.7 +/- 2.1 years; eight underwent anterior and posterior spinal fusions (AF and PF, respectively) two weeks apart (group A), four underwent PF alone (group B), and one had a three-stage procedure. Mean total respiratory elastance (Ers), static and dynamic lung elastance (Est,L and Edyn,L, respectively), chest wall elastance (Ew), and lung resistance (RL) were derived according to previously described methodology. In group A, Ers and Ew increased by 39 percent and 58 percent, respectively, following AF and by 20 percent and 129 percent following PF, while Est,L and Edyn,L did not change or declined following PF. Lung resistance increased 19 percent and 41 percent by the end of AF and PF, respectively, in group A. In group B, Ew more than doubled, resulting in a 39 percent increase in Ers. Increases in Ers, Ew, and respiratory flow resistance observed at the time of spinal corrective surgery for kyphoscoliosis may result from rib cage trauma and changes in airway caliber related to microatelectasis and uneven distribution of mechanical properties within the lungs. Spinal correction results in immediate and short-term deterioration of respiratory mechanics measured under anesthesia. PMID- 2331913 TI - Intrapulmonary vascular dilatations (IPVD) in liver transplant candidates. Screening by two-dimensional contrast-enhanced echocardiography. AB - Intrapulmonary vascular dilatations (IPVD) are extrahepatic complications of acute and chronic liver disorders that can result in severe hypoxemia. Contrast enhanced (CE) echocardiography provides a noninvasive method to detect right-to left shunting associated with IPVD. We prospectively studied 40 consecutive liver transplant candidates to determine the relationship between CE echocardiography, arterial blood gases, and standard pulmonary function tests. Two patients had technically unacceptable results of echocardiographic studies. Thirty-eight patients had acceptable results of studies; seven (18.4 percent) of 38 were hypoxemic (PaO2 less than 70 mm Hg). Thirty-one patients (81.6 percent) had PaO2 greater than or equal to 70 mm Hg. Positive CE echocardiograms suggesting IPVD were found in five (13.2 percent) of 38. Three (9.7 percent) of the 31 patients with PaO2 greater than or equal to 70 mm Hg had positive CE echocardiograms. Two (28.6 percent) of the seven hypoxemic patients had positive CE echocardiography. Mean PaO2 and pulmonary function parameters were not significantly different between those with positive CE echocardiogram compared with those with normal CE echocardiograms. We conclude that for our group of liver transplant candidates, (1) IPVD as suggested by CE echocardiography were not uncommon (13.2 percent), and (2) positive CE echocardiography could be documented in patients who were not hypoxemic (9.7 percent). PMID- 2331915 TI - One-year longitudinal study of a no-smoking policy in a medical institution. AB - Smoking and health are increasingly understood to be incompatible. To evaluate, prospectively and retrospectively, the attitudes of employees, staff physicians, and patients of a medical institution, a questionnaire was administered before and after implementation of a no-smoking policy. Of many questions, select ones reviewed here focused on the following concerns: (1) how tobacco smoke affects employees and patients, (2) employee acceptance of a no-smoking policy before and after its implementation, and (3) the consequences of the policy on employee smokers. Open-ended questions about smoking were constructed by a committee comprised of clinicians, investigators, and administrators. The questionnaire was given to 2,000 randomly selected patients and the institution's entire staff of 4,200 employees and 225 staff physicians. Data were obtained on three occasions: six months before, six months after, and one year after the implementation of the no-smoking policy. The majority of patients, employees, and physicians indicated that the smoke of others bothered them and ranked the following as most offensive: smell, eye irritation, provocation of sinus problems, coughing, and headache. Approximately 80 percent of employees and patients favored the policy before its inception; and employees increasingly favored it through the year after its implementation with a favorable attitude increasing by nearly 10 percentage points. One year after implementation, 80 percent of patients were in favor of the policy. In the final survey, 74 percent of respondents indicated the policy had helped them. One year after policy implementation, employee smoking was reduced significantly from 22 to 14 percent; and of those employees who continued to smoke, 81 percent smoked less than eight cigarettes per day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331914 TI - Respiratory failure caused by adiaspiromycosis. AB - Adiaspiromycosis is a rare pulmonary disorder caused by the fungus Emmonsia crescens (or Chrysosporium parvum var crescens). According to the amount of inhaled conidia, man may develop symptomatic disease. After reaching the alveoli, the adiaconidia do not multiply or disseminate, but will induce a granulomatous inflammatory reaction that may lead to fatal respiratory failure. Up to now, only five cases of disseminated pulmonary infection have been documented. This work describes the occurrence, in Brazil, of two further cases of symptomatic disease with diffuse interstitial infiltrates and severe functional impairment. Possible massive infestation during activities in closed and stuffy environments is suggested. The specific diagnosis was troublesome and could not be made by cultures, skin tests or bronchoalveolar lavage. Both patients were successfully treated, but a spontaneous resolution of the process is seriously considered. PMID- 2331916 TI - Cutaneous masses, rib lesions, and chylous pleural effusion in a 20-year-old man. PMID- 2331917 TI - Advocate's disease. PMID- 2331918 TI - Diagnosis of peripheral lung cancer using a new type of endoscope. AB - A new fiberoptic bronchoscope, the BF-2.2T, has been designed to go through the 2.6-mm channel of the conventional fiberoptic bronchoscope (Olympus BF-1T20). It measures 2.2 mm in outer diameter; it has a visual angle of 75 degrees, a range of observation of 3 to 50 mm, an effective length of 1,150 mm, and a total length of 1,400 mm. It bends at 120 degrees in an upward direction and at 120 degrees in a downward direction. The 2.2-mm tip of the BF-2.2T bends like a conventional fiberoptic bronchoscope, and this is the main characteristic of this instrument. The BF-2.2T facilitates clinically satisfactory observation and photography, as a method for detecting peripheral lung cancer. PMID- 2331919 TI - Bronchoscopy in the management of bronchopleural fistula. PMID- 2331920 TI - Figure-eight kinking of the aorta (pseudocoarctation) coexistent with coarctation. AB - An asymptomatic young man presented with a cardiac murmur and hypertension only in the right arm. Angiograms showed kinking of the aortic arch with a figure eight appearance consistent with pseudocoarctation. Before the kinked segment, also demonstrated were a stenotic lesion in the aortic arch proximal to the left carotid artery and profound collateral circulations in the right thorax. These findings strongly suggested a rare combination of pseudocoarctation and true coarctation. His hypertension was corrected following surgery with a bypass graft between the ascending aorta and the abdominal aorta. PMID- 2331921 TI - Pulmonary function changes in the acute stage of histoplasmosis, with follow-up. An analysis of eight cases. AB - We have studied eight patients, six children and two adults, during a microepidemic of soil- and patient-proven histoplasmosis. Pulmonary function tests were performed between the 15th and 23rd days after the onset of symptoms, and repeated between the fifth and sixth, the ninth and tenth and the 15th and 22nd months afterward. Initial abnormalities were mild in seven cases and severe in one. There was a restrictive pattern in three cases and an obstructive pattern in two. The fraction of CO extraction was reduced in five cases and the diffusing capacity for CO was reduced in five of six cases so tested. Hypoxemia was present in three cases. On follow-up, the obstructive defect had disappeared by the sixth month, the restrictive pattern by the tenth month, and the diffusing defect still remained in three cases by the end of follow-up. Hypoxemia remained only in the severe case. PMID- 2331922 TI - Left main-stem bronchial stenosis complicating bronchial artery embolization. AB - A 36-year-old patient was found to have severe left main-stem bronchial stenosis two years after bronchial artery embolization (BAE) for hemoptysis. Embolization induced bronchial ischemia appeared to be the only potential cause for the observed lesions, and, to our knowledge, this constitutes the first report of late bronchial sequelae following BAE. Despite balloon-catheter dilatation of the stenosis, the severity of poststenotic lesions led to left pneumonectomy. The anatomic data further supported the hypothesis of a complication of BAE. Clinicians and radiologists should be aware of this potential complication of a widely used therapeutic procedure. PMID- 2331923 TI - Pulmonary edema associated with electrical injury. AB - The occurrence of cardiogenic pulmonary edema following alternating current electrical injury has not been reported. A patient developing severe pulmonary edema immediately following an electrical injury-induced episode of ventricular fibrillation is described. Evidence that the etiology of the pulmonary edema was cardiogenic is derived from both hemodynamic data and the calculation of the pulmonary edema fluid to serum colloid osmotic pressure ratio. PMID- 2331924 TI - Right-to-left shunting through a patent foramen ovale without pulmonary hypertension. Transient improvement after balloon catheter closure. AB - A patient had a history of right tuberculosis and severe hypoxemia secondary to right-to-left shunting through a patent foramen ovale without pulmonary hypertension. A balloon tip catheter was positioned in the left atrium and retracted against the atrial septum and the hypoxemia was temporarily resolved. PMID- 2331925 TI - MRI of Askin's tumor. Case report at 1.5 T. AB - This represents the first case of an Askin's tumor demonstrated on MRI. It showed a large pleural-based mass which trapped pleural fluid in large pseudotumors. The disease was unilateral and involved the mediastinum as well. Magnetic resonance imaging was helpful in demonstrating extrathoracic disease in the area of the right brachial plexus. PMID- 2331926 TI - Tension hydrothorax in a patient with renal failure. AB - A patient with renal failure who received acute peritoneal dialysis rapidly developed a tension hydrothorax which required immediate drainage of the pleural space. Rapid identification and therapeutic intervention for this rare complication of peritoneal dialysis is necessary because of its life-threatening potential. PMID- 2331927 TI - Growth and development of lungs in siblings with nonimmune hydrops. AB - Postmortem findings in the lungs of two siblings with nonimmune hydrops and lung hypoplasia are presented. In one, a girl, the hypoplasia was severe, with reduced numbers of airway generations and markedly reduced radial alveolar counts. In the other, a boy, the hypoplasia of both airway and alveolar development was mild. The reason for the difference in the growth of the lungs in these two children is unknown. The additional finding of Noonan's syndrome in the male sibling with mild hypoplasia and in the father is of interest. PMID- 2331928 TI - Primary testicular choriocarcinoma with pulmonary metastases presenting as ARDS. AB - We report a case in which ARDS was the presenting manifestation of testicular choriocarcinoma with numerous metastases to the lungs. We also review the literature on other cases in which ARDS developed as a result of neoplastic infiltration of the lungs and stress the fact that it may be indistinguishable from ARDS from other causes. Because potentially effective chemotherapy for the neoplastic processes most commonly involved (ie, germ cell tumors, acute leukemia and lymphoma) is available, we emphasize the importance of considering a neoplastic disorder in the differential diagnosis of cases of otherwise unexplained ARDS. Early accurate diagnosis could conceivably result in an improved outcome in these cases. PMID- 2331929 TI - Hypervitaminosis A following long-term use of high-dose fish oil supplements. AB - The use of various dietary supplements containing fish oils has become popular as a method of reducing the risk of developing cardiovascular disease. However, consumption of large amounts of these substances may pose some potential hazards. Described herein is a patient who developed hypervitaminosis A after prolonged fish oil supplement ingestion. PMID- 2331930 TI - Abnormal lung gallium-67 uptake preceding pulmonary physiologic impairment in an asymptomatic patient with Pneumocystis carinii pneumonia. AB - Pneumocystis carinii pneumonia was suggested by a diffuse, bilateral pulmonary uptake of gallium-67 in an asymptomatic, homosexual male with the antibody to the immunodeficiency virus (HIV) who was undergoing staging evaluation for lymphoma clinically localized to a left inguinal lymph node. Chest radiograph and pulmonary function evaluation, including lung volumes, diffusing capacity and arterial blood gases, were within normal limits. Bronchoalveolar lavage revealed Pneumocystis carinii organisms. In this asymptomatic, HIV-positive patient, active alveolar infection, evidenced by abnormal gallium-67 scanning, predated pulmonary physiologic abnormalities. This observation raises questions concerning the natural history of this disease process and the specificity of physiologic tests for excluding disease. It also has implications for the treatment of neoplasia in the HIV-positive patient population. PMID- 2331931 TI - Sarcoidosis presenting as progressive ascending lower extremity weakness and asymptomatic meningitis with hypoglycorrhachia. AB - A 26-year-old man developed progressive weakness over a two-month period. His chest radiograph showed diffuse interstitial infiltrates, and transbronchial lung biopsies demonstrated noncaseating granulomas consistent with sarcoidosis. Sarcoid neuropathy should be considered in the differential diagnosis of the patient presenting with an atypical Landry-Guillain-Barre syndrome. PMID- 2331932 TI - Exogenous lipoid pneumonia due to inhalation of spray lubricant (WD-40 lung). AB - An elderly woman developed lipoid pneumonia due to the inhalation of mist from a spray lubricant that she was using as a liniment for sore back and neck muscles. This unusual practice is reported to be common among older people bothered by rheumatism. The potential for this complication to occur in other patients leads us to present this case report. PMID- 2331933 TI - Maternal theophylline consumption and the risk of stillbirth. AB - Women in the Collaborative Perinatal Project who received theophylline during pregnancy were no more likely to be delivered of a stillborn infant than were women who did not receive theophylline. These findings add to the safety record associated with maternal receipt of theophylline during pregnancy. PMID- 2331934 TI - Enzymes and exertion. PMID- 2331935 TI - Simultaneous bilateral bullectomy, parietal pleurectomy and right upper lobectomy via median sternotomy. PMID- 2331936 TI - Treating asthma. PMID- 2331937 TI - Flow volume loop. PMID- 2331938 TI - Catheter complications. PMID- 2331939 TI - Tuberculous pericarditis and AIDS. PMID- 2331940 TI - Caffeine and methylxanthines. PMID- 2331941 TI - Situs inversus totalis and lung cancer. PMID- 2331942 TI - Hypodermic needle aspiration in a freebase cocaine abuser. PMID- 2331943 TI - Sleep apnea investigations. PMID- 2331944 TI - Behcet's disease with half and half nail and pulmonary artery aneurysm. PMID- 2331945 TI - Skunk lung. PMID- 2331946 TI - Alpha 1-antitrypsin deficiency registry. PMID- 2331947 TI - Selective bronchial suctioning. PMID- 2331948 TI - Complete disclosure? PMID- 2331949 TI - Right atrial myxoma. PMID- 2331950 TI - Endoscopic photodynamic therapy with hematoporphyrin derivative for primary treatment of gastrointestinal neoplasms in inoperable patients. AB - Endoscopic photodynamic therapy with hematoporphyrin derivative was used in the primary treatment of 54 patients with inoperable gastrointestinal neoplasms. Patients were divided into three groups including 24 with esophageal squamous cell carcinoma, 14 with adenocarcinoma of the stomach or lower third of the esophagus, and 16 with rectosigmoid adenocarcinoma. After infusion of 2.5-5.0 mg hematoporphyrin derivative/kg of body weight, lesions were photoradiated using an argon dye laser with power set at 300-400 mW for 5 min/site. During a follow-up period averaging 14.5 months (range 1-33 months), complete local tumor destruction and negative histology were observed in 24 of 54 cases. The mean recurrence-free period varied from 13.8 to 17.4 months according to groups. Fifteen patients remain alive and disease-free. The results of this open pilot study suggest the potential efficacy of photodynamic therapy as curative treatment for selected cases of inoperable gastrointestinal cancers, possibly in association with locoregional radiotherapy. PMID- 2331951 TI - Fate of antacid gel in the stomach. Site of action and interaction with food. AB - The site of action of a high-power Al-Mg antacid gel (buffering capacity 70 meq/10 ml) and its interaction with food was examined in 10 healthy volunteers. Combined pH-metries in antrum and corpus were performed in each volunteer on four occasions. In a randomized study design, antacid or placebo were given 1 hr after either a protein or a carbohydrate pancake, of which only the former had any acid buffering capacity. Before the meal, pH was higher in the antrum than in the corpus (median antrum: 3.2, corpus 1.5). In the corpus, a protein pancake but not a carbohydrate pancake raised the pH (median pH after protein pancake: 3.5; after carbohydrate pancake: 1.4). In the antrum, the protein pancake had no effect, but the carbohydrate pancake decreased the pH (median pH after protein pancake: 3.1; after carbohydrate pancake: 2.0). The antacid had no effect in the corpus after either pancake. It raised intraluminal pH markedly in the antrum after a carbohydrate pancake (median antral pH before antacid: 2.0; after antacid: 3.3), whereas its effect in the antrum was weak after a protein pancake. In vitro experiments were conducted to explain the in vivo results: in contrast to a carbohydrate pancake, a protein pancake reduced the buffering capacity of the antacid by direct interaction. In conclusion, the effect of an antacid gel on intragastric pH is predominantly localized in the antrum and is attenuated in the presence of proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331952 TI - Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Correlation with endogenous prostaglandin E2. AB - The effects of zinc L-carnosine on ethanol-induced damage and the correlation of these effects with endogenous prostaglandin E2 were evaluated in rat gastric mucosa in vivo and in vitro. When given either intragastrically or intraperitoneally, zinc L-carnosine (10 or 30 mg/kg) prevented gross visible damage to gastric mucosa caused by ethanol without affecting the mucosal prostaglandin E2 level. This protective effect of zinc L-carnosine was not inhibited by indomethacin. Histological assessment showed that zinc L-carnosine inhibited deep mucosal necrosis, as did 16,16-dimethyl prostaglandin E2. Zinc L carnosine (10(-6) or 10(-5) M) inhibited the damage caused by ethanol to gastric cells isolated from rat gastric mucosa in vitro; this effect was not inhibited by indomethacin. The results suggested that zinc L-carnosine protects the gastric mucosa and enhances cellular resistance to ethanol without the mediation of endogenous prostaglandins. PMID- 2331953 TI - Effect of intravenous omeprazole on intragastric pH during intravenous infusion of amino acids. AB - Intravenous amino acids stimulate gastric acid secretion by an unknown mechanism. In patients on parenteral nutrition, this amino acid-induced gastric acid secretion might contribute to the failure of H2-receptor antagonists to raise intragastric pH above 4.0, a level thought to be needed to prevent stress ulceration. Therefore we studied the effect of single and repeated doses of the H+/K(+)-ATPase blocker omeprazole on the intragastric pH during a 3-hr infusion of amino acids in 10 healthy volunteers; 5% glucose was used as a control infusion. Amino acids significantly decreased intragastric pH when compared to glucose infusion (P less than 0.05). After intravenous administration of 40 mg, 80 mg and 2 X 40 mg omeprazole, this amino acid-induced fall in pH was significantly inhibited (P less than 0.01). No advantage of the 80-mg dose over the 40-mg dose could be demonstrated. The repeated dose of 40 mg showed a tendency to higher pH values compared to the single-dose experiments, which reached significance in the amino acid experiments only (P less than 0.05). Neither during the infusion of amino acids nor the glucose infusion omeprazole was able to continuously raise intragastric pH above 4.0. In conclusion, this study shows that intravenous omeprazole prevents gastric acid stimulation by intravenous amino acids but fails to continuously raise intragastric pH above 4. PMID- 2331954 TI - Idiopathic autonomic denervation in eight patients presenting with functional gastrointestinal disease. A causal association? AB - Gut dysmotility may result from disease of the extrinsic neural pathways supplying the gut. We report the results of studies on sweating, cardiovascular, and sudomotor reflexes in eight prospectively evaluated patients with apparently functional gastrointestinal disorders. There was no personal or family history of neurologic disease, except for one patient with known atony of the bladder. Motility of the esophagus, stomach, and small intestine were, respectively, abnormal in two, six, and seven patients and showed either uncoordination of contractions between segments or postcibal hypomotility. All had generalized or patchy anhidrosis; quantitative sudomotor axon reflex tests were also abnormal in four patients and borderline in one. Plasma levels of catecholamines were abnormal in one patient. All patients had evidence of sympathetic denervation: preganglionic in two patients, postganglionic in five patients, and mixed in one patient. Three patients also had abnormal heart-rate responses to deep breathing, suggesting parasympathetic dysfunction. No underlying cause for the autonomic dysfunction was identified in any of these patients despite extensive investigations. Thus, these data support the hypothesis that apparently functional gastrointestinal disorders may be due to idiopathic autonomic denervation. PMID- 2331955 TI - Motor responsiveness of proximal and distal human colonic muscle layers to acetylcholine, noradrenaline, and vasoactive intestinal peptide. AB - There is an increasing body of evidence suggesting regional heterogeneity in human colonic function. Using circular and longitudinal muscle strips from proximal and distal human colon, the present study sought to determine whether such regional differences were apparent in smooth muscle responsiveness to neurohumoral agents. Both proximal and distal muscle gave quantitatively similar responses to acetylcholine, as they did for noradrenaline. However, the circular muscle of the distal colon was more sensitive to vasoactive intestinal peptide than was the circular muscle of the proximal colon. Longitudinal muscle from both regions was comparatively insensitive to VIP. PMID- 2331956 TI - Prolonged anorectal manometry and external anal sphincter electromyography in ambulant human subjects. AB - We have developed a method for prolonged combined anorectal manometry and electromyography (EMG) of the external anal sphincter in ambulant subjects. Fourteen healthy volunteers were studied for a total of 284 hr (mean of 20.3 hr/subject). Anorectal manometry was performed using a probe with twin pressure sensors. EMG was recorded by one indifferent and two differential silver-silver chloride surface electrodes positioned 0.5-0.75 cm from the anus on either side. The sampling reflex occurred frequently and was significantly (P less than 0.001) more common during wakefulness than during sleep and also following meals than during fasting (P less than 0.01). The passage of flatus was associated with transient relaxation of the anal canal in 19% of episodes. In contrast, there was a contractile episode with no preceding relaxation in 75% of episodes. The anal sphincter had significantly (P less than 0.05) more action potentials (APs) during the day (12.8 +/- 3.2 APs/10 min) than at night (1.6 +/- 1.3 APs/10 min). During micturition, anal canal pressure rose (mean 15 mm Hg) in association with powerful external anal sphincter contractions. Our data show that, normally, contractile activity both in the anal canal and external anal sphincter maintains fecal continence during micturition and the passage of flatus. The technique should lead to a better understanding of the normal mechanisms of fecal continence during waking and sleep and of the pathophysiology of disorders of anorectal function. PMID- 2331957 TI - Double-blind comparison of cisapride and cimetidine in treatment of reflux esophagitis. AB - In a double-blind, randomized, comparative trial of the prokinetic drug cisapride and the H2-blocker cimetidine, mucosal healing and changes in symptoms of gastroesophageal reflux were evaluated in patients with erosive reflux esophagitis. The patients were treated with either cisapride, 10 mg four times a day (N = 36) or cimetidine, 400 mg four times a day (N = 37) for six weeks, or for 12 weeks if mucosal healing was not obtained by week 6. Upon entry, two thirds of the patients in each group had grade I (Savary-Miller) esophagitis, and the remainder grade II or III. At the end of treatment, endoscopy showed mucosal healing in 56% (38-72%; 95% confidence interval) of cisapride and 57% (39-73%; 95% confidence interval) of cimetidine patients. After six weeks, both drugs significantly (P less than 0.01) decreased the intensity and frequency of heartburn, regurgitation, and the postural syndrome. No significant intergroup differences were found regarding endoscopic parameters or the improvement of heartburn and regurgitation. Concomitant antacid use was also comparable. Adverse effects were reported by four cisapride and nine cimetidine patients. These results indicate that the effects of cisapride compare well with those of cimetidine in terms of both esophageal mucosal healing and symptom relief. PMID- 2331958 TI - Cure of arthritis-dermatitis syndrome due to intestinal bypass by resection of nonfunctional segment of blind loop. AB - Many complications that followed jejunoileal bypass operations performed for the relief of morbid obesity were caused by bacterial overgrowth in the excluded blind loop. The arthritis-dermatitis syndrome was one of the common distressing disorders. The pathogenetic mechanism was thought to be an immune-complex mediated process related to bypass enteritis. Antiarthritic medication was ineffective in most instances, and the skin lesions were refractory to treatment. A 45-year-old woman was suffering from the disorder as described above. She also had diarrhea, a low hematocrit, an elevated white blood cell count, and an increased sedimentation rate. Her nutritional status was satisfactory, presumably because of adaptive hypertrophy of the short functioning small intestinal segment. The patient adamantly refused dismantling of the bypass or any gastric restriction operations. Therefore, the blind loop, the source of her disease, was excised with immediate relief of all ill effects and restoration of normal laboratory findings. The patient has been entirely well since, and her weight has remained stable for one year. PMID- 2331959 TI - Ruptured mycotic pseudoaneurysm of the gastroduodenal artery presenting with hemoperitoneum and subcapsular liver hematoma. AB - We report a case of a patient with mycotic pseudoaneurysm of the gastroduodenal artery who presented with hemoperitoneum and subcapsular hematoma of the liver. The diagnosis was established with contrasted abdominal CT scanning. Visceral angiography was not needed. Prompt recognition and surgical intervention led to a favorable outcome. Pseudoaneurysm of visceral vessels is an uncommon disease process, and to our knowledge, this is the first reported case that has presented with free blood in the peritoneal cavity and beneath the liver capsule. This case may also represent a rare complication of therapeutic ERCP procedures. Mycotic aneurysm or pseudoaneurysm of visceral vessels may develop from bacteremia and its dissection or rupture should be suspected in patients presenting with sepsis and abdominal pain. PMID- 2331960 TI - MPTP and duodenal motility. PMID- 2331961 TI - MPTP, gastroduodenal motility, duodenal ulceration, and Parkinson's disease. PMID- 2331962 TI - Hypertensive lower esophageal sphincter and dysphagia. PMID- 2331963 TI - A villous adenoma of the distal duodenum treated by laser therapy. PMID- 2331964 TI - A captive audience. PMID- 2331965 TI - The role and importance of position statements. PMID- 2331966 TI - The group process approach to research: a successful experience. PMID- 2331967 TI - Renal and retinal complications in insulin-dependent diabetes mellitus: the art of changing the outcome. AB - Over the past decade much has been learned about the relationship between good glycemic control and the alteration or prevention of long-term renal and retinal complications of insulin-dependent diabetes mellitus. The challenge for diabetes health professionals is to translate knowledge into improved patient care. A model program, using a multidisciplinary team approach, is presented to show how the art of changing the outcome can be incorporated into each patient encounter through screening, education, and counseling. PMID- 2331968 TI - [Analysis of reproductive parameters in mare herds of the chief and state stud farms at Marbach and Schwaiganger]. AB - The paper analyses different parameters of fertility in mares of different breeds. Totally 2794 cycles of the years 1973 to 1985 have been investigated. PMID- 2331969 TI - [The occurrence of hereditary congenital arthromyodysplasia (arthromyodysplasia congenita hereditaria) in calves of the Hessian cattle population]. AB - The Arthromyodysplasia congenita hereditaria is marked by the flexion and fixation of the front leg joints. The statistic analysis of all available data from 536 calves showed that male calves and twins are significantly more affected. The course, duration and delivery date in the pregnancy of cows with arthromyodysplastic calves showed no peculiarity. Concomitant defects of arthromyodysplasia of the forelimbs were spine- and heart defects and neuromyodysplasia of the hind legs. Three bulls KUR, KER and ALD were ancestors of 37% of all registered calves. This frequency of arthromyodysplasia in the bloodline of these three bulls seem to be a sign for a genetic factor with a strong penetrance in male calves. PMID- 2331970 TI - [Contamination of public children's playgrounds in Hannover with helminth eggs]. AB - Fifty-two public sand pits on children playgrounds in Hannover were investigated for the presence of parasites. A large proportion (63.5%) of these playgrounds were contaminated with parasite eggs. Eggs from Toxocara spp., Toxascaris leonina and other common helminth parasites were found in 55.8%, 9.6% and 26.1% of these playgrounds, respectively. A total of 208 sand samples were collected, and 30.8% of them contained eggs from Toxocara spp. (24.5%), Toxascaris leonina (2.4%) or other common helminths (9.1%). In 45.1% of the Toxocara positive samples, the eggs were embryonated. Eggs from Toxocara spp. were found in 33.0%, 31.0% or 14.0% of samples from districts with low, medium or high numbers of dogs per hectare, respectively. PMID- 2331971 TI - [Results of liver function tests in abomasal displacement and ketosis of cattle]. AB - Totally 187 cows were used in this research, 101 of these had left and 60 right abomasal displacement. The rest of them had ketosis. Blood and urine samples were collected from all of the cows for laboratory analyses. The amount of bile acid and total bilirubin and activity of aspartate aminotransferases (AST) in blood samples and the amount of ketone in the urine samples were determined. The results obtained from this study were as follows: The mean value of bile acid, total bilirubin and AST-activity were 38.37 mumol/l, 13.06 mumol/l and 92.26 U/l in right abomasal displacement cows and 37.93 mumol/l, 14.39 mumol/l and 68.39 U/l in left abomasal displacement cows respectively. Although important differences (P less than 0.05) were detected in AST-values between these three groups of diseases, there was no significant differences in bile acid and total bilirubin. There was a correlation between total bilirubin and bile acid and total bilirubin and AST in the right and left abomasal displacement cows. Same correlation was determined between total bilirubin and AST in acetonemic cows. But there was no correlation between total bilirubin and bile acid in acetonemic cows and between bile acid and AST in abomasal displacement and acetonemic cows. A very important connection was determined between the amount of total bilirubin and degree of the acetone in the urine (P less than 0.001) of the left abomasal displacement cows. The same connection (P less than 0.05) was determined between the degree of the acetone in the urine and AST-activity in the same cows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2331972 TI - [Seroepidemiologic studies of the detection of antibodies to Brucella, Chlamydia, Leptospira, BVD/MD virus, IBR/IPV virus and enzootic bovine leukosis virus (EBL) in dromedary mares (Camelus dromedarius)]. AB - Camels which are bred for the purpose of racing were tested serologically for 6 different animal diseases. The group were split into racing and breeding camels. The following results were achieved: Brucellosis, breeding camels 2%, racing camels 6.6%; Chlamydiosis 24%, 15%; Leptospirosis 2.5%, 5.6%; BVD/MD 9.2%, 3.6%. No antibodies were detected against IBR/IPV- and EBL-virus. The results are discussed under an epidemiological point of view. PMID- 2331973 TI - Illness intrusiveness and quality of life in end-stage renal disease: comparison and stability across treatment modalities. AB - Investigated the degree to which chronic, life-threatening illness and its treatment interfere with continued involvements in valued activities and interests--that is, illness intrusiveness--and its impact on quality of life in end-stage renal disease. Data were collected on two occasions separated by a lag of 6 weeks. Mixed analyses of variance indicated that life domains were affected differentially across treatments. Perceived illness intrusiveness correlated significantly with treatment time requirements, uremic symptoms, intercurrent nonrenal illnesses, fatigue, and difficulties in daily activities. Significant quality-of-life differences were observed across treatment modalities for satisfaction/happiness and pessimism/illness-related concerns but not for depression/distress. Perceived illness intrusiveness correlated significantly with each of these quality-of-life measures. Results were stable over time. These findings substantiate the construct of illness intrusiveness as a mediator of the psychosocial impact of chronic, life-threatening illness. PMID- 2331974 TI - Some variables affecting dentists' assessment of patients' distress. AB - Dental students estimated the pain distress and discomfort of their patients after patients received a Class II restoration (simple filing). Dentist's estimates of patient pain accounted for 36% of the variance in patient self report responses. Dentist accuracy was significantly lower, however, for estimates of anxiety and distress. Dentist accuracy was unaffected by patient's degree of self-monitoring. There was a tendency for female dentists to demonstrate greater accuracy than male dentists, but this effect was nonsignificant. In addition, dentists' accuracy in assessing overall patient discomfort was significantly lower in that segment of the treatment procedure that was most stressful for the dentists. This article discusses theoretical explanations for this latter effect. PMID- 2331975 TI - Encouraging the practice of testicular self-examination: a field application of the theory of reasoned action. AB - Identified factors associated with testicular self-examination (TSE) within the context of the theory of reasoned action. Subjects (232 male college students) received instruction in TSE and completed a questionnaire operationalizing the components of the theoretical model. During the following 6 weeks, a field intervention was conducted in which approximately half the subjects were exposed to posters reminding them to perform the exam. Multiple-regression analyses revealed that intention to perform TSE correlated significantly with attitude and subjective norm and that consideration of self-efficacy and TSE knowledge improved the prediction of intention. Significant differences in outcome expectancies and normative beliefs were found between subjects who intended to perform the exam and those who did not. Intention was moderately (r = .30, p less than .001) correlated with behavior; the intention-behavior correlation, however, was stronger among subjects who intended to perform the exam and were exposed to the posters (r = .55, p less than .001). PMID- 2331976 TI - Effects of a waking schedule on primary enuretic children treated with full spectrum home training. AB - Examined the effects of adding a waking schedule to full-spectrum home training (FSHT) for primary enuresis. Twenty children received FSHT, and 17 children received FSHT plus a waking schedule. The groups did not reliably differ in average bedwettings per week in treatment and length of treatment. Also, the groups did not reliably differ with respect to proportion of treatment successes and proportion of relapses at 1-year follow-up. Further, across both treatment groups, 76% achieved a dry bed, and only 16% experienced a relapse by 1-year follow-up. Although results support the efficacy of FSHT, the beneficial effects of a waking schedule reported previously were not replicated. The findings suggest the need for closer examination of individual differences among children with primary nocturnal enuresis. PMID- 2331977 TI - Parental injury prevention endeavors: a function of health beliefs? AB - Investigating parents' beliefs about injury prevention may yield important information for planning preventive interventions. A comprehensive description of parents' beliefs about injury prevention is presented in this study, and effects of child age and sex are described. In addition, a health belief model was successfully used to predict parent-reported teaching of safety skills and preventive environmental interventions. The model successfully cross-validated the prediction in two independent samples. Parents reported low feelings of susceptibility or worry about injury. The variables most associated with parental preventive endeavors were the belief that intervention can avoid injury, a realistically high appraisal of the amount of time involved, and feelings of high knowledge and competence to teach safety skills. Implications of these data for designing more effective behavioral interventions are described. PMID- 2331978 TI - The contribution of personality characteristics to the relationship between social support and perceived physical health. AB - Although a great deal of research has been conducted on the relationship between social support and physical health, the contribution of personality characteristics to this relationship has rarely been assessed. Structural equation modeling was employed to derive and test a model of the direct and indirect relationships between personality characteristics, social network size, the perceived availability of support, socially supportive behaviors, and perceived physical health with a sample of Pennsylvania adults. Significant paths indicate that individuals who perceive themselves as affiliative and as help seekers and help givers report larger social networks, receive more socially supportive behaviors, and perceive that more support is available to them. The perception that support is available shared a direct relationship with perceived physical health. The utility of including multiple measures of social support and personality characteristics related to receiving support in investigations of the relationship between social support and physical health is discussed. PMID- 2331979 TI - Age and sex differences in health habits and beliefs of schoolchildren. AB - All children in Grades 3 through 12 of one school system completed a survey about health habits and beliefs including smoking and eating habits, perceptions of exercise, weight, and parental involvement in health. The surveys were factor analyzed within grade and sex, and the overall factors that emerged were Smoking Habits, Family Discussion of Health, Family Thinking About Health, Nutritional Habits, and Health Locus of Control. Analysis of variance of each factor revealed that girls generally reported healthier food habits than did boys. However, girls reported more smoking and less exercise. There are also changes in habits and belief with age; junior high school is a particularly important time for the development of several habits. The findings are discussed in relation to theories of child development and the implications for the content and timing of future health education intervention programs with children. PMID- 2331980 TI - Type of hemodialysis and preference for behavioral involvement: interactive effects on adherence in end-stage renal disease. AB - Examined the effects of hemodialysis type (i.e., staff controlled, in center vs. patient controlled, home) and patient preference for behavioral involvement on adherence and emotional adjustment in a sample of 53 patients with end-stage renal disease. Consistent with person x treatment interaction models, higher levels of preference for behavioral involvement were associated with better dietary adherence (i.e., lower serum potassium) for patients receiving dialysis at home but worse dietary adherence for patients receiving treatment in a dialysis center. A similar though weaker patient x treatment type matching pattern was observed for fluid-intake adherence (i.e., interdialytic weight gain). No effects were observed for patients' self-reported depression levels. Possible mechanisms for the interactional effect on adherence are discussed. PMID- 2331981 TI - Evaluation of genotoxic effects of the herbicide dicamba using in vivo and in vitro test systems. AB - The genotoxic effects of the herbicide dicamba have been studied by measuring 1) the unwinding rate of liver DNA from intraperitoneally (i.p.) treated rats (fluorimetric assay); 2) DNA repair as unscheduled DNA synthesis (UDS) induced in cultured human peripheral blood lymphocytes (HPBL); and 3) sister chromatid exchanges (SCE) in HPBL. Results show that dicamba is capable of inducing DNA damage since it significantly increases the unwinding rate of rat liver DNA in vivo and also induces UDS in HPBL in vitro in the presence of exogenous metabolic activation (S-9 mix). Furthermore, dicamba causes a very slight increase in SCE frequency in HPBL in vitro. PMID- 2331982 TI - Induction of nuclear aberrations by smokeless tobacco in epithelial cells of human oral mucosa. AB - Cytologic and cytogenetic studies were performed to assess the prevalence of somatic cell genetic damage in 48 young adults equally divided to represent users and nonusers of smokeless tobacco. Exposure was ascertained by measuring saliva cotinine using capillary gas chromatography. Squamous epithelial cells sampled from the oral mucosa demonstrated significant cytologic alterations associated with tobacco exposure. The frequency of micronucleated cells was significantly (P less than .01) higher in the labial mucosa of exposed (2.22%) compared to unexposed (0.27%) individuals. The frequency of micronuclei varied widely between exposed subjects but was higher in heavily (2.48%) compared to lightly (1.29%) exposed individuals as measured by saliva cotinine levels. Morphologic classification of epithelial cell nuclei showed that the frequency of cells with normal nuclear structure was significantly (P less than .01) reduce in exposed individuals. Analysis of oral epithelial cells of five additional nonusers of smokeless tobacco but wearers of orthodontic appliances to stimulate abrasion demonstrated no difference from the nonexposed control group. Unlike the case with cigarette smokers, peripheral lymphocyte sister-chromatid exchange frequency was not affected by exposure to smokeless tobacco. The oral cytology data, however, support an interpretation of exposure-dependent nuclear alterations, including micronuclei, in the oral epithelium associated with the use of smokeless tobacco. Altogether, results suggest that use of smokeless tobacco may cause genetic damage to cells in the oral epithelium. PMID- 2331983 TI - Purification and properties of L-aspartate aminotransferase of Chlamydomonas reinhardtii. AB - An enzyme which catalyzes the transamination of L-aspartate with 2-oxoglutarate has been purified 400-fold to electrophoretic homogeneity from the unicellular green alga Chlamydomonas reinhardtii 6145c. An apparent relative molecular mass of 138,000 was estimated by gel filtration. The enzyme is a dimer consisting of two identical subunits of Mr 65,000 each as deduced from PAGE/SDS studies. A stoichiometry of two molecules pyridoxal 5-phosphate/enzyme molecule was calculated. The enzyme has an isoelectric point of 8.48 and its absorption spectrum exhibits a maximum at 412 nm which is shifted to 330 nm upon addition of L-aspartate. L-Aspartate or pyridoxal 5-phosphate, but not 2-oxoglutarate, protected the enzyme from heat inactivation. The purified enzyme was able to transaminate, although to a low extent, L-phenylalanine and L-tyrosine with 2 oxoglutarate, and L-serine, L-alanine and L-glutamine with oxaloacetate. L Aspartate aminotransferase exhibited hyperbolic kinetics for 2-oxoglutarate and oxaloacetate, and nonhyperbolic behaviour for L-aspartate and L-glutamate. Apparent Km values were 0.55 mM for 2-oxoglutarate, 0.044 mM for oxaloacetate, 2.53 mM for L-aspartate and 3.88 mM for L-glutamate. Transamination of L aspartate in C. reinhardtii is a bisubstrate reaction with a bi-bi ping-pong mechanism, and is not inhibited by substrates. PMID- 2331984 TI - Purification and characterization of a cytosolic protein-tyrosine kinase from porcine spleen. AB - A cytosolic protein-tyrosine kinase has been highly purified from porcine spleen using [Val5]angiotensin II as a substrate. The purification procedure involves sequential column chromatographies on phosphocellulose, Sephacryl S-200, casein Sepharose 4B, heparin-Sepharose CL-6B and anti-(4-aminobenzyl phosphonic acid)- Sepharose 4B. Analysis of the most highly purified preparation by SDS/PAGE revealed a major silver-stained band of molecular mass 40 kDa. The 40-kDa cytosolic protein-tyrosine kinase was purified approximately 10,000-fold with an overall yield of about 7%. It had autophosphorylation activity which was carried out by intramolecular catalysis. The stoichiometry of phosphate incorporation was about 1 mol phosphate/mol enzyme. In the autophosphorylation reaction, the apparent Km value for ATP was relatively low, 0.35 microM; Mn2+ was slightly preferred to Mg2+ as divalent cation. [Val5]Angiotensin II phosphorylation activity of the 40-kDa kinase increased with the amount of phosphate incorporated into the enzyme. A phosphate exchange reaction was observed during the autophosphorylation. These results suggest that the 40-kDa kinase described here is a different type of protein-tyrosine kinase than the enzymes so far reported. PMID- 2331985 TI - Side chain mobility in bovine calbindin D9k. Rotational motion of Tyr13. AB - The local motion of Tyr13 in wild type and mutant calbindin (Mr 8500, 75 amino acids) was investigated by time-resolved fluorescence spectroscopy performed at the MAX synchrotron in Lund, Sweden. Two-dimensional fluorescence spectroscopy (excitation-emission mapping) was used to characterize the emission of Tyr13 against the background of phenylalanine residues in the presence and absence of Ca2+. Local restricted motion of Tyr13 is observed in wild-type calbindin with only minor differences between the Ca2(+)-saturated and Ca2(+)-free forms. In a mutant, where Pro20 is exchanged for Gly and Ala14 and Asn21 are deleted, the local mobility of Tyr13 is enhanced close to values characteristic for free rotational diffusion. An increase of the overall rotational motion in this mutant form by a factor of two and the enhanced local mobility of Tyr13 indicate local and global conformational changes that also affect the Ca2(+)-binding properties. Tyr13 occurs in two isomeric species differing in lifetime of the excited state; the major species is populated to 85-90%. PMID- 2331986 TI - Occurrence of tyrosine sulfate in proteins--a balance sheet. 1. Secretory and lysosomal proteins. AB - 1. The abundance of tyrosine sulfate in secretory proteins and in various classes of cellular proteins has been quantified and compared to protein-bound carbohydrate sulfate. 2. HepG2 cells and fibroblasts, two cell types showing only the constitutive pathway of secretion, and PC12 cells, which show both the constitutive and the regulated pathway of secretion, were subjected to pulse chase and/or long-term labelling with [35S]sulfate and [3H]tyrosine, followed by analysis of proteins in the cells and medium. Under both conditions of labelling, 65-92% of the protein-bound tyrosine sulfate and 44-84% of the protein-bound carbohydrate sulfate were found to be secretory. In HepG2 cells, the frequency of sulfation of tyrosine residues, which can be determined independently from protein abundance and the rate of protein synthesis, was 8-22 times higher in proteins secreted into the medium than in cellular proteins. 3. All cell lines studied contained significant amounts, not only of carbohydrate sulfate, but also of tyrosine sulfate in specific cellular proteins. As shown for fibroblasts, these tyrosine-sulfated proteins were retained within the cells for at least 100 min of chase following a pulse with [35S]sulfate and were almost completely recovered in a light membrane fraction after subcellular fractionation. 4. Lysosomes were found to contain small, but significant, amounts of protein-bound tyrosine sulfate in addition to protein-bound carbohydrate sulfate. Protein-bound tyrosine sulfate in lysosomes reached a peak at 20 min of chase and rapidly disappeared thereafter, whereas protein-bound carbohydrate sulfate accumulated after 20 min of chase. Examination of the known sequences of eleven lysosomal enzymes revealed the presence of potential tyrosine sulfation sites in five of them. 5. Our results show that secretory proteins are the most abundant, but not exclusive, in vivo substrates for tyrosine sulfation and suggest the presence of soluble tyrosine-sulfated proteins in lysosomes and other, as yet unidentified, organelles of the secretory pathway. In the following paper in this journal we describe the abundance of tyrosine sulfate in integral membrane proteins. PMID- 2331987 TI - Occurrence of tyrosine sulfate in proteins--a balance sheet. 2. Membrane proteins. AB - 1. The abundance of tyrosine sulfate in membrane proteins was quantified in four different cell lines and compared to that in soluble cellular and secreted proteins. 2. Upon metabolic labelling of HepG2, Ltk-, AtT20 and PC12 cells with [35S]sulfate or [3H]tyrosine, a fraction enriched in integral membrane proteins was found to contain small, but significant, amounts of protein-bound tyrosine sulfate (up to 2.5% of the total cellular plus secreted protein-bound tyrosine sulfate). On the other hand, the frequency of sulfation of tyrosine residues of membrane proteins was within the same order of magnitude as that of secreted proteins, indicating that the low abundance of tyrosine sulfate in membrane proteins was largely a reflection of the low abundance of these proteins themselves. Consistent with this conclusion were the results of an analysis showing that 14 out of 32 selected membrane-spanning proteins contain potential tyrosine sulfation sites. 3. In HepG2 cells, three tyrosine-sulfated integral membrane glycoproteins of molecular mass 100, 125 and 150 kDa were identified. Characterization of the 150-kDa tyrosine-sulfated membrane protein revealed that it was protected from proteolysis in intact cells, suggesting a localization in an intracellular organelle. 4. Together with the results reported in the preceding paper in this journal, our data suggest that tyrosine sulfation occurs in various classes of trans-Golgi-derived proteins, soluble as well as membrane, and extracellularly exposed as well as intracellularly retained, proteins. This suggests that tyrosine sulfation may have a variety of physiological functions, depending on the individual tyrosine-sulfated protein or protein class. PMID- 2331988 TI - Study of a series of analogs of salmon calcitonin in which alanine replaces leucine. AB - Leucine residues at positions 12, 16 and 19 of salmon calcitonin were systematically replaced by alanine either one, two or three at a time. Substitution of Ala at positions 12 or 16 had the greatest effect on the structure of the peptide and on the ability of the peptide to attain structures of higher helical content in the presence of lipid. Despite the similar effects on the conformational properties, the effects on activity are markedly different for analogs with Ala substitutions at positions 12 and 16. The Ala12 derivatives are much less active while the Ala16 derivatives are slightly more active than the parent hormone. In contrast to the effects of substitutions at these positions, substitution of Ala at position 19 has relatively little effect on activity or on conformation. These results demonstrate that different regions of the calcitonin molecule have different conformational requirements for maximal activity. PMID- 2331989 TI - Localization of the peptidase activity of human serum butyrylcholinesterase in a approximately 50-kDa fragment obtained by limited alpha-chymotrypsin digestion. AB - Purified human serum butyrylcholinesterase (approximately 90-kDa subunit) is known to exhibit aryl acylamidase and peptidase activity. Limited alpha chymotrypsin digestion of the purified butyrylcholinesterase gave three major protein fragments of approximately 50 kDa, approximately 21 kDa and approximately 20 kDa. In our earlier studies [Rao and Balasubramanian (1989) Eur. J. Biochem. 179, 639-644] we characterized the approximately 20-kDa fragment and showed that it exhibited both butyrylcholinesterase and aryl acylamidase activities. In the present studies the approximately 50-kDa fragment is characterized. This fragment, after isolation by Sephadex G-75 chromatography from a chymotryptic digest of purified butyrylcholinesterase, exhibited only peptidase activity and was devoid of cholinesterase and aryl acylamidase activities. It could bind to a column of Ricinus communis agglutinin bound to Sepharose, indicating its glycosylated nature and the presence of galactose. The peptidase activity in the approximately 50-kDa fragment could be immuno-precipitated by a polyclonal antibody raised against purified butyrylcholinesterase. SDS-gel electrophoresis of this fragment isolated by R. communis agglutinin-Sepharose and Sephadex G-75 chromatography showed a protein band of approximately 50 kDa by silver staining. Amino-terminal sequence analysis of the approximately 50-kDa fragment gave the sequence of Gly-Pro-Thr-Val-Asp which corresponded to amino acid residues 291-295 in the butyrylcholinesterase sequence [Lockridge et al. (1987) J. Biol. Chem. 262, 549-557]. The combined results suggested that alpha-chymotrypsin digestion of human serum butyrylcholinesterase resulted in the formation of a approximately 20-kDa fragment exhibiting both cholinesterase and aryl acylamidase activities and a approximately 50-kDa fragment exhibiting only peptidase activity. PMID- 2331990 TI - The interaction of Triton X-100 with purple membranes. Detergent binding, spectral changes and membrane solubilization. AB - The interaction of the non-ionic surfactant Triton X-100 with Halobacterium purple membranes has been examined at sublytic and lytic surfactant concentrations. These membranes present a number of important peculiarities in their behaviour towards the surfactant. Although solubilization is a very slow process, with a half-time of the order of hours, detergent binding appears to occur at the same fast rate as that found in other membranes. Lipids are solubilized more easily than proteins, so that hardly any protein is solubilized at surfactant concentrations at which about 75% of the lipid is in the form of detergent-mixed micelles; once started, protein solubilization takes place within a narrow range of surfactant concentrations. Retinal provides a built-in probe to monitor detergent-induced conformational changes by spectroscopy in the visible range. No spectral variation is detected at the prelytic stage, i.e. when detergent is incorporated into the membrane in monomeric form. Membrane disruption is accompanied by a blue shift in the absorption maximum, retinal isomerization (from all-trans to 13-cis), and a decrease in specific absorbance (bleaching). Increasing detergent concentrations after solubilization is completed do not produce further shifts in the spectral maximum, but the specific absorbance is progressively decreased. It is shown that Triton X-100 has a complex effect on the retinal chromophore, modifying its configuration and microenvironment (changes in maximum wavelength) and promoting hydrolysis of the retinal-bacteriorhopsin Schiff's base (bleaching). PMID- 2331991 TI - Interactions between glutamine metabolism and cell-volume regulation in perfused rat liver. AB - 1. In the presence of near-physiological glutamine concentrations, exposure of perfused rat liver to hypotonic perfusion media switched glutamine balance across the liver from net release to net uptake. This was due to both stimulation of flux through glutaminase and inhibition of flux through glutamine synthetase. Conversely, during exposure to hypertonic media, net glutamine release from the liver increased due to inhibition of glutaminase flux and slight stimulation of flux through glutamine synthetase. The effect of perfusate osmolarity on glutaminase flux was observed at an NH4Cl concentration (0.5 mM) sufficient for near-maximal ammonia stimulation of glutaminase. This indicates the involvement of different mechanisms of glutaminase flux control by extracellular osmolarity changes and ammonia. The effects of anisotonicity on flux through glutamine metabolizing enzymes were fully reversible. Glutamine (0.6 mM) stimulated urea synthesis from NH4Cl (0.5 mM) during hypotonic and normotonic conditions. 2. Exposure to hypotonic and hypertonic media led, after initial liver-cell swelling and shrinkage, respectively to volume-regulatory K+ fluxes which largely restored the initial liver-cell volume despite the continuing osmotic challenge. Even after completion of cell-volume regulatory K+ fluxes, the effects of perfusate osmolarity on hepatic glutamine metabolism persisted. This indicates that in anisotonicity the liver cell is left in an altered metabolic state, even after completion of volume-regulatory responses. 3. During perfusion with isotonic media, addition of glutamine (3 mM) led to an increase of liver mass by about 4% within 2 min, which was accompanied by a net K+ uptake by the liver. Thereafter, the new steady state of increased liver mass was maintained throughout glutamine infusion. When the liver mass had reached this new steady state, a net release of K+ from the liver of about 3 mumol/g liver was observed during the following 10 min. Withdrawal of glutamine was followed by a slow reuptake of K+ and the liver mass returned to its initial value. Following exposure to glutamine (3 mM), the intracellular glutamine concentration (as calculated from glutamine tissue levels, taking into account the extracellular space determined with the [3H]inulin technique) rose from about 1 mM to 30-35 mM within about 12 min, indicating a 10-12-fold concentrative uptake of glutamine into the liver cells and an osmotic challenge for the hepatocyte. When intracellular glutamine had reached its steady-state concentration, net K+ efflux from the liver was also terminated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2331992 TI - Fate of interleukin-6 in the rat. Involvement of skin in its catabolism. AB - Iodinated recombinant human interleukin-6 (125I-rhIL-6) was intravenously injected into rats and its fate was studied during 24 h. Between 10-20 min after a single-dose injection, 125I-rhIL-6 accumulated in liver as previously reported [Castell et al. (1988) Eur. J. Biochem. 177, 357-361]. After 1 h, the radioactivity disappeared from the liver and accumulated in skin, reaching 35% of injected 125I-rhIL-6 5-8 h after injection. No comparable accumulation of radioactivity was found in skin when [125I]iodide or rat serum 125I-albumin was administered. Finally the radioactivity was detected as [125I]iodide in urine. Autoradiographic analysis of skin sections 5 h after 125I-rhIL-6 injection showed radioactivity in the interstitium. When the experiments were carried out with [35S]rhIL-6, essentially the same results were obtained: a decrease in radioactivity in the liver after 20 min, and a substantial increase in skin 7 h after injection. In vitro experiments showed that 125I-rhIL-6 is degraded by rat and human fibroblasts, whereas no degradation was observed with rat hepatoma cells (Fao) or human hepatocytes. These observations suggest the involvement of skin in the catabolism of IL-6. PMID- 2331993 TI - Isolation and characterization of a cDNA encoding porcine gastric haptocorrin. AB - A cDNA encoding the gastric haptocorrin was isolated from a porcine gastric mucosal lambda gt11 cDNA library using oligonucleotide probes. The 1.4-kb cDNA contains a 1.25-kb open reading frame and 178 nucleotides of 3' noncoding region. Although no initiator methionine is present, primer extension analysis indicated that the transcription initiation site is only 100 bp upstream of the 5' end of this clone. Northern blot analysis showed that a single mRNA species of 1.6 kb exists in hog gastric mucosa. There was no cross-hybridization between this cDNA and the mRNA for haptocorrin in rat submaxillary gland or gastric RNA by Northern blot analysis. This lack of cross-reactivity was also seen on Southern blots, where cow, sheep and dog but neither rat nor mouse genomic DNAs showed cross hybridizing bands. Comparison of the deduced amino acid sequence of this cDNA with that previously reported for rat intrinsic factor [Dieckgraefe, B.K. et al. (1988) Proc. Natl Acad. Sci. USA 85, 46-50] showed considerable similarity, suggesting that these cobalamin-binding proteins may have a common evolutionary origin. PMID- 2331994 TI - Structure-function relationships in the polypeptide cardiac stimulant, anthopleurin-A. Effects of limited proteolysis by trypsin. AB - Selective proteolysis of the polypeptide cardiostimulant anthopleurin-A by trypsin introduces a single break in the polypeptide backbone on the C-terminal side of Arg14. The resulting derivative is devoid of any cardiostimulant activity. The structural changes which accompany this loss of activity have been examined by one- and two-dimensional 1H-NMR spectroscopy. It is shown that the overall backbone folding of anthopleurin-A is conserved on digestion, with some structural changes occurring for residues which are adjacent to the site of cleavage by trypsin. Thus, although previous NMR studies on anthopleurin-A indicate that the region surrounding Arg14 is devoid of any ordered structure, it appears that some degree of structural integrity is required to allow the essential side chains to adopt the conformation necessary to produce a cardiostimulant effect. PMID- 2331995 TI - Structure determination of the major N- and O-linked carbohydrate chains of the beta subunit from equine chorionic gonadotropin. AB - The carbohydrate moieties of equine chorionic gonadotropin alpha and beta subunits were released from the protein backbones by successive treatments with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F and alkaline borohydride and then fractionated by FPLC and HPLC. The major N- and O-linked glycans of the beta subunit were characterized by 500-MHz 1H-NMR spectroscopy, showing a remarkable structural heterogeneity for the N-glycosidically linked chains, comprising mono-, di-, tri- and tri'-antennary N-acetyllactosamine type of glycans, being partly alpha 1-6 fucosylated at the Asn-bound GlcNAc residue and having alpha 2-6 and alpha 2-3 linked N-acetyl- and N-acetyl-4-O acetylneuraminic acid residues as sialic acid constituents. Significant differences in this respect were detected for the partially characterized glycans of the alpha subunit. The major part of the O-linked carbohydrate chains, occurring solely in the beta subunit, is formed by tri-, tetra-, penta- and hexa saccharides. There are indications for the presence of oligo(N-acetyllactosamine) units in both the N- and O-linked glycans of the beta subunit. PMID- 2331996 TI - Prognostic significance and therapeutic implications of silent myocardial ischaemia. PMID- 2331997 TI - Serum cholesterol distribution, measurement frequency and cholesterol awareness in three geographical areas of Finland. AB - The serum cholesterol distribution in three geographical areas of Finland was examined during the first and the second FINMONICA surveys in 1982 and 1987. The mean serum cholesterol concentration changed very little during this observation period. In 1987 the population mean (+/- SD) was 6.12 +/- 1.26 mmoll-1 in men aged 25-64 years and 5.96 +/- 1.28 mmoll-1 in women. Only approximately 20% of the Finns had their serum cholesterol at the level which is regarded as desirable by recent international recommendations. The frequency of cholesterol measurements increased in Finland, especially in North Karelia, from 1972 to 1977 but since then no further increase has taken place. From 1982 to 1987 the proportion of subjects whose cholesterol level was over 6.5 mmoll-1 and who reported knowing that their cholesterol was high increased from 27% to 31% in men and from 24% to 34% in women, respectively. It is concluded that approximately 45% of the adult Finnish population is at moderately increased risk and further 33% at considerably increased risk of coronary heart disease because of the elevated serum cholesterol. PMID- 2331998 TI - Vagal heart rate control after percutaneous transluminal coronary angioplasty. AB - Impairment of vagal heart rate control is common in coronary artery disease. To evaluate whether percutaneous transluminal coronary angioplasty (PTCA) has any beneficial effect on this impairment we measured heart rate responses to deep breathing and to standing up, standard tests of cardiac parasympathetic activity, in 28 patients before and 4 weeks after successful PTCA. Before PTCA, 10 patients (36%) had an abnormal heart rate response to deep breathing and one patient (4%) an abnormal response to standing up. The heart rate responses did not change significantly from the preoperative values after PTCA. Thus, the relief of critical coronary obstruction by PTCA seems to have no beneficial effect on vagal heart rate control. PMID- 2331999 TI - Use of a new removable vena cava filter in order to prevent pulmonary embolism in patients submitted to thrombolysis. AB - The authors present a removable vena cava filter that may be introduced percutaneously, is atraumatic to the venous wall, and permits the simultaneous use of thrombolytic therapy. Sixty-five patients were studied: 42 cases of pulmonary embolism with threatening venous thrombosis; 23 cases of phlebitis associated with an ilio-caval thrombus without pulmonary embolism. The filter was introduced 38 times femorally and 27 times by a jugular approach. In 16 cases (24.6%) clots broke loose, were effectively caught by the filter, and were progressively dissolved during thrombolytic therapy. The filter remained in place on average 4.5 +/- 1.2 days. The filter was removed in all cases without provoking the recurrence of pulmonary embolism. Two deaths, not related to pulmonary embolism, occurred during hospitalization. Phlebography, performed in all cases before and after treatment, showed a significant decrease of the phlebographic score (10.88 +/- 0.82 vs 6.77 +/- 0.86, P less than 0.001). The same was observed in 40 patients who underwent a pulmonary angiography before and after treatment (Miller index = 17.04 +/- 0.73 vs 5.49 +/- 0.87, P less than 0.0001). After removal of the filter, no sign of pulmonary embolism was detected on lung scan in the 23 patients with ilio-caval thrombus alone. More than 5 g (100 ml)-1 of haemoglobin was lost by 15.38% of patients. All patients were followed-up for a mean of 7.12 +/- 1.3 months; in no case was there any clinical recurrence of pulmonary embolism. Thus this device allows an effective temporary filtering of the vena cava.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332000 TI - Intra-arterial blood pressure monitoring in the evaluation of the hypertensive athlete. AB - To compare the blood pressure (BP) changes during a long-distance run with those during bicycle ergometry, nine normotensive and 18 hypertensive joggers were studied by means of ambulatory intra-arterial monitoring. In all subjects the ergometric test caused a progressive increase in systolic and little change in diastolic BP. Exertional BP levels were closely related to pre-exercise baseline values (P less than 0.001). A different BP pattern was observed during track running, as a sharp rise in systolic BP reaching maximum values 2-4 min after the start was recorded. Subsequently, systolic BP progressively declined throughout the run, only to increase again during the final sprint. Diastolic BP fell markedly at the onset of the run and then remained substantially stable throughout. A poor relationship was observed between the BP values at peak exercise and baseline levels (P less than 0.05) as the normotensives showed a significantly higher BP response than the hypertensives. On the contrary, during the ergometric test a parallel increase in BP was recorded in the normotensive and the hypertensive joggers. No correlation was found between the BP response to track running and to bicycle ergometry. These results indicate that the BP response to a standard stress test is not predictive of the BP changes determined by a long-distance run. The BP increase with strenuous effort seems to be reduced in hypertensive individuals, probably because of latent impairment of cardiac performance. PMID- 2332001 TI - Errors in measurements of stroke volume for invasive and echo-Doppler evaluations of valvular regurgitant fractions. Clinical evaluation and computer simulation. AB - The aim of this study was to compare cardiac catheterization (CATH) with 2D echo Doppler (ED) in clinically evaluating the stroke volumes (SV) needed to calculate aortic and mitral regurgitant fractions (aortic and mitral SV for the ED method, thermodilution and angiographic SV for the CATH). As there is no 'gold standard' for this kind of measurement, only subjects without valvular regurgitation were considered. In these subjects, though the two SV measurements needed to calculate the regurgitant volume should have been identical, there was, in fact a difference due to the systematic and random errors of the methods. We calculated the mean value and the standard deviation of this difference in a series of patients without valvular regurgitation in order to obtain an estimate of both systematic and random errors. In 20 patients studied by ED a difference of 11.9 +/- 16.7 ml was found. In 36 patients studied by cardiac catheterization the difference was 19.6 +/- 20.1 ml. A significant systematic error was found for both ED and the invasive method; The transmitral SV tended to be larger than the aortic and the angiographic SV larger than that obtained by thermodilution. To try to determine the extent to which the random errors could be attributed to the reproducibility of the measurements, we carried out computer simulations. The SVs of 50 000 hypothetical patients were randomly generated and then attributed a random error calculated on the basis of the variability of the CATH (thermodilution 4%, angiography 10%) and the ED measurements (aortic annulus 6%, mitral annulus 18%, mitral time velocity integral 10%, aortic time velocity integral 8%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332002 TI - Electrophysiologic testing after aortic valve replacement in two patients with aortic stenosis and preoperative ventricular fibrillation. AB - In two patients with severe aortic stenosis successful resuscitation from ventricular fibrillation was documented by Holter recording/ECG monitoring. After aortic valve replacement programmed ventricular stimulation was performed in both patients, but ventricular tachycardia/ventricular fibrillation was not inducible. The patients were left without antiarrhythmic therapy and have been free from cardiac events for 18 and 20 months, respectively. The prognostic value of postoperative electrophysiologic testing after aortic valve replacement in patients with severe aortic stenosis and preoperative resuscitation is discussed. PMID- 2332003 TI - Severe thrombosis during oestrogen treatment for tall stature. AB - This case report illustrates that the risk of thromboembolism in the treatment of tall girls with high dose oestrogens is not negligible. PMID- 2332004 TI - Prevalence of congenital adrenal hyperplasia in Kuwait. AB - Between 1978 and 1988 congenital adrenal hyperplasia (CAH) was diagnosed in 60 children in Kuwait with an estimated prevalence of 1:9,000 livebirths, which is higher than that reported from Europe and Canada. In addition, there was presumptive evidence of CAH resulting in the death of 20 other children, giving a prevalence figure of 1:7000. There were 41 girls (68%) and 19 boys (32%). Thirty one of the girls (75.6%) and 11 of the boys (57.9%) were saltlosers. Fifty-four patients (90%) were diagnosed as 21-hydroxylase deficient, 3 patients (5%) had a deficiency of the 3 beta-hydroxy-steroid dehydrogenase enzyme, and 3 patients (5%) showed a deficiency of 11 beta-hydroxylase. PMID- 2332005 TI - [15N]methacetin urine test: a method to study the development of hepatic detoxification capacity. AB - The [15N]methacetin urine test was used to study human O-demethylase activities to characterize the maturation of hepatic detoxification capacity. The study involved 43 healthy subjects aged 1 day-47 years. The urinary 15N elimination rates were measured following oral administrations of an aqueous [15N]methacetin solution. Age-dependent normal values of hepatic drug elimination capacity were established. Parameters were the 15N elimination half-life and cumulative elimination of the 15N dose as a percentage over a 9 h period. The maximum elimination rate (% dose/h) and peak time can give additional information. The 15N method is a simple, non-invasive and non-radioactive liver function test avoiding disadvantages of 14C and 13C breath tests. The [15N]methacetin test is suitable and useful in studying the hepatic development at birth and pathological changes of the microsomal detoxification capacity in early childhood. PMID- 2332006 TI - Influence of intrauterine growth retardation on parameters of liver function in low birth weight infants. AB - To establish nutritional management of low birth-weight infants according to their individual metabolic situation, hepatocellular partial function was studied in 13 appropriate (AGA) and 11 small-for-gestational-age (SGA) low birthweight (LBW) infants during the first weeks of postnatal life. The concentrations of total bile acids and of alpha-amino-nitrogen in serum, the renal excretion of urea and ammonia and the renal excretion of 15N after enteral administration of 3 mg 15N-labeled methacetin/kg were measured. In comparison to AGA infants, SGA infants had elevated serum concentrations of total bile acids and of alpha-amino nitrogen, decreased excretion of urea, increased excretion of ammonia in urine, and lower urinary 15N-excretion after enteral administration of 15N-labeled methacetin. The data suggest that hepatocellular functions are influenced by intrauterine growth retardation resulting in a reduced metabolic capacity in SGA infants. The metabolic differences between SGA and AGA infants should be considered in the nutritional management of LBW infants. PMID- 2332007 TI - Minor morphological aberrations in children with isolated urinary tract malformations. AB - The prevalence of 54 minor morphological aberrations (MMAs) (mild malformations, dysplasias, deformities and phenogenetic variants) was determined in 138 children with isolated malformations of the urinary tract and in 32 patients with multiple major birth defects including renal malformations. Children with infectious diseases matched to each patient by sex, age and ethnic origin served as controls. The overall prevalence of MMAs--expressed as MMA/subject ratio--proved to be significantly higher in patients with multiple malformations (2.50) than in those with isolated renal abnormalities (0.80) and in controls (0.76). The difference between the latter two groups was not significant. Apart from characteristic patterns of well-defined syndromes, the only specific association found was the higher prevalence of supernumerary nipples in patients with isolated (and hidden) urinary tract abnormalities of various types (9.4% versus 1.8% in controls; P less than 0.005). PMID- 2332008 TI - Radiological "metamorphosis" in a patient with severe congenital osteogenesis imperfecta. AB - Congenital osteogenesis imperfecta (OI) was diagnosed by ultrasound in a 31-week old fetus, and the diagnosis confirmed after delivery by caesarean section at week 36. The baby survived the neonatal period, but failed to thrive, had recurrent respiratory infections and ultimately died at 8 months. Cultured fibroblasts synthesized both normal type I collagen and unstable type I collagen harbouring a structural defect in the alpha 1 (I) cyanogen bromide-derived peptide number 8 (CB8) region of the molecule, indicating a heterozygous dominant mutation. At birth, the radiological picture was that of the "thin bone"-type of congenital OI (OI type IIB/III in the Sillence classification); at the age of 12 weeks ribs and long bones had undergone a marked expansion giving a very different picture, that of the "thick bone"-type congenital OI (OI type IIA). The mechanism responsible for this change in bone structure is not known, but fractures and callus formation are unlikely to be the only factors. Caution is needed in the interpretation of radiographs of newborns with OI for prognostic or genetic purposes. PMID- 2332009 TI - Birth distribution in cystic fibrosis and phenylketonuria. AB - The present study of 977 cystic fibrosis (CF) patients showed a bimodal birth distribution with peaks in April to July and October to January. After adjustment to the monthly variation of the birth rate of all liveborn children there was no significant deviation from the expected distribution. The 387 phenylketonuria (PKU) patients showed no seasonal birth variation. PMID- 2332010 TI - In vivo propionate oxidation as a prognostic indicator in disorders of propionate metabolism. AB - Biochemical markers such as plasma and urinary metabolite concentrations and in vitro enzyme activity are of limited prognostic value in the most common disorders of propionate metabolism, methylmalonic acidaemia (MMA) and propionic acidaemia (PA). In vivo propionate oxidation was compared with conventional prognostic measures as predictors of clinical severity in seven children with MMA and six with PA. Propionate oxidation was measured using a continuous infusion of [1-13C]propionate and was expressed as the rate of appearance of 13CO2 as a percentage of the propionate infusion rate. Children with MMA (mean oxidation 51.2%, range 17.5-91.6, P less than 0.05) and with PA (mean oxidation 36.3%, range 3.0-91.1, P = NS) oxidised substantially less propionate than controls (mean oxidation 81.9%, range 69.4-101.0, n = 5). Percentage oxidation was a better predictor of the clinical severity score (r = 0.75, P less than 0.01) than was in vitro enzyme activity, plasma propionate or methylmalonate concentration or urinary metabolite excretion. Studies were repeated after an interval of 1-3 weeks in six of the subjects; the percentage oxidation in each subject was virtually unchanged between studies (coefficient of variation 8.6%). These results suggest that in vivo oxidation measurements using [13C]propionate are both reproducible and prognostically useful in disorders of propionate metabolism. PMID- 2332012 TI - C-reactive protein and bacterial infection in preterm infants. AB - Serum C-reactive protein (CRP) concentration was measured by a new solid phase ligand-binding radiometric monoclonal antibody immunoassay in a prospective study of 193 consecutively born preterm infants. In 104 with no clinical or laboratory evidence of infection the median CRP in cord serum was 0.125 mg/l (range 0.011 6.0 mg/l), at 24 h it was 1 mg/l (0.016-7.0) and at 48 h 2 mg/l (0.400-8.0). The present highly sensitive assay has enabled these normal ranges to be defined for the first time, at levels below the threshold of non-labelled immunoassays and of all commercially available CRP assays. The values in cord serum were significantly lower than in normal healthy adults (median 0.8 mg/l, range 0.07-29 mg/l, n = 468). Arterial catheterisation and endotracheal intubation, in the absence of infection, did not appear to elevate CRP, nor did cerebral germinal layer or intraventricular haemorrhage. Among nine infants with confirmed septicaemia eight had a serum CRP level raised at least once during the first 48 h and serum CRP in the other one increased 250-fold in 24 h before treatment was started. Using this assay, serum CRP is a useful and rapidly available adjunct to clinical assessment in diagnosis and exclusion of bacterial infection in the early neonatal period, has encouraged us to withhold or discontinue antibiotics and also has a role in monitoring response to treatment. PMID- 2332011 TI - Methylmalonic aciduria with homocystinuria: biochemical studies, treatment, and clinical course of a Cbl-C patient. AB - A patient with infantile onset methylmalonic aciduria and homocystinuria (Cbl-C mutant) is described. Therapy with hydroxycobalamin, folate and vitamin B6 improved his condition. As hypomethioninaemia and homocystinaemia persisted, he was treated with intramuscular methylcobalamin, but without success. Treatment with betaine started at 25 months of age, normalized plasma methionine and elicited disappearance of homocystinaemia. Results of biochemical studies in cultured fibroblasts paralleled those described for other Cbl-C patients except that methylmalonyl-coenzyme A mutase activity in disrupted fibroblasts was in the normal range. PMID- 2332013 TI - Continuous cerebral electrical impedance monitoring in sick preterm infants. AB - Cerebral electrical impedance (dZ) and intra-arterial blood pressure were measured continuously during the first 48 h after birth in 26 sick ventilated preterm infants with a birth weight less than 1500 g. The aim was to establish whether any patterns of dZp or the variability of either blood pressure or dZp would allow identification of those infants who developed intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) or a poor neurological outcome. IVH and PVL were diagnosed by ultrasound image obtained every 6 h. Cerebral electrical impedance recordings were unsuitable for analysis in three patients and a further three died within 14 h of birth. In the remaining 20 patients, no step changes that may have been related to the onset of IVH or PVL were evident and whilst three patterns of dZp were identified, they were not useful in distinguishing between normal infants or those who developed IVH, PVL or had a poor neurological outcome. Using multiple linear regression, the coefficient of variation of dZp was significantly associated with both IVH and outcome, as was the coefficient of variation of blood pressure. Continuous measurement of cerebral electrical impedance, whilst technically feasible in sick preterm infants, was not found useful as a method of identifying those who developed IVH, PVL or had a poor neurological outcome. PMID- 2332014 TI - Necrotizing enterocolitis after intravenous immunoglobulin treatment for neonatal isoimmune thrombocytopenia. AB - A male neonate of 38 weeks' gestation with isoimmune neonatal thrombocytopenia treated with high dose intravenous immunoglobulin (IVIG) developed necrotizing enterocolitis (NEC) at 3 days of age. The known maternal and neonatal risk factors for the development of this disease were excluded. The association between high dose IVIG and the appearance of thrombotic events might be another aetiological factor for occurrence of NEC in a newborn infant. PMID- 2332015 TI - Micturition habits and incontinence in 7-year-old Swedish school entrants. AB - The prevalence of incontinence in children has been extensively studied, but knowledge of other bladder symptoms is lacking in a healthy child population. The micturition habits of 3556 7-year-old school entrants were surveyed by a questionnaire supplemented by telephone interviews. One or more symptoms of a disturbed bladder function was reported in 26%, but most of these had moderate urgency as a sign of incomplete voluntary bladder control. Isolated bedwetting occurred in 2.8% of the girls and 7.0% of the boys, whereas nocturnal incontinence combined with daytime wetting was equally common in both sexes, 2.3% and 2.0% respectively. Diurnal incontinence was reported in 6.0% of the girls and 3.8% of the boys and was usually combined with other symptoms. The frequency of micturition in children without symptoms of bladder disturbance and with no previous urinary tract infection was 3-7 times per day. PMID- 2332016 TI - Impaired zinc metabolic status in children affected by idiopathic nephrotic syndrome. AB - Zinc content of serum, hair and erythrocytes, urinary zinc excretion, zinc clearance (CZn) and the ratio of CZn to creatinine clearance (CCr) (CZn/CCr) were measured in 32 children aged between 2.1 and 14.4 years suffering from idiopathic nephrotic syndrome (INS) without renal failure (CCr greater than 70 ml/min 1.73 m2 body surface area). Nineteen subjects had proteinuria and the remaining 13 were in remission. All children received calcium and vitamin D supplementation while on steroid therapy. There was high dietary zinc and protein intake. The results were compared with those obtained from 19 healthy subjects (aged 2-14 years). Zinc concentration in serum, erythrocytes and urine were measured by a colourimetric method. Proton induced X-ray emission was used to determine zinc content in hair. In patients both with and without proteinuria, the mean contents of serum, hair and erythrocytes were significantly lower than in the control group. The urinary zinc excretion, CZn and CZn/CCr in INS children were significantly higher than in the control group. A positive correlation was found between urinary zinc and protein excretion. In spite of high dietary zinc intake and normal intestinal absorption, children with INS had a zinc deficiency. This was probably caused by an increased urinary zinc loss. PMID- 2332017 TI - Efficacy of cyclosporin A for idiopathic pulmonary fibrosis. AB - In an 11-year-old girl with severe dyspnoea and cyanosis, idiopathic pulmonary fibrosis (IPF) was diagnosed. The PaO2 of blood could be maintained between 50 mm Hg and 70 mm Hg with a high dose pulse corticosteroid therapy, although this dose could not be reduced. Azathioprine in addition to prednisolone provoked deterioration. Twelve weeks after admission, cyclosporin A (Cs A), a known immunosuppressant, was started together with prednisolone. The PaO2 reverted to normal within 1 month and prednisolone could be tapered off within 6 months. Two years after admission, the patient is free of symptoms on continuous Cs A therapy. This case seems to be the first case successfully treated with Cs A. PMID- 2332018 TI - Growth hormone response to exercise in asthmatic and normal children. AB - Maximal growth hormone (GH) increments following exercise were compared in asthmatic (n = 14) and normal (n = 8) children. Exercise, which consisted of 6 min ergometer cycling while breathing cold dry (CD) air, induced asthma in all asthmatic patients but not in normal subjects. Baseline plasma GH levels were similar in both groups. Following exercise, however, asthmatic patients had significantly higher mean GH increments than normal subjects (14.8 vs 4.9 ng/ml, P less than 0.025). To evaluate the possible role of bronchoconstriction in the GH response all subjects exercised again, this time while breathing warm humid (WH) air. Despite the absence of exercise-induced asthma (EIA) while breathing WH air, asthmatic patients still had significantly higher mean GH increments than normal subjects (9.2 vs 2.3 ng/ml, P less than 0.05). We conclude that some asthmatic children show excessive GH secretion after exercise regardless of inspired air conditions or the development of EIA. PMID- 2332019 TI - Misleading radiology following bone marrow transplantation for infantile osteopetrosis. PMID- 2332020 TI - Steroid treatment in myalgia due to familial Mediterranean fever. PMID- 2332021 TI - Serum soluble CD8 antigen level is not elevated in mucocutaneous lymph node syndrome (Kawasaki disease) in spite of an increase in serum soluble interleukin 2 receptors. PMID- 2332022 TI - Prereferral intervention: a prescriptive approach. AB - This investigation assessed effects of three increasingly inclusive versions of the Behavioral Consultation (BC) model on problem behavior of students in mainstream classrooms in an effort to develop an effective and efficient approach to prereferral intervention. Subjects were 43 general educators, their 43 most difficult-to-teach students (without disabilities), and 12 school consultants, representing seven inner-city middle schools. Teachers and students were assigned to three BC groups, representing least (BC 1), more (BC 2), and most (BC 3) inclusive variants of BC, and one control group. Preintervention, postintervention, and follow-up observations of student behavior indicated that more inclusive BC versions exerted stronger effects than the least inclusive variant in reducing problem behavior. Theoretical and practical implications for consultation-related activity are discussed. PMID- 2332023 TI - Are regular education classes equipped to accommodate students with learning disabilities? AB - This study examined educational practices in regular education classes in grades K-5 to determine changes required to facilitate a full-time mainstreaming program for students with learning disabilities. Data collected during the planning year of a mainstreaming project permitted a detailed analysis of the elementary school and the extent to which it accommodated individual differences. Data from informal and structured observations, interviews, and surveys of students, parents, and teachers suggested that fundamental changes in instruction are necessary for the regular education initiative to work in this school. PMID- 2332024 TI - Effects of self-evaluation on the independent work skills of preschool children with disabilities. AB - This study examined the effects of a self-evaluation treatment package on the independent work skills of preschool children with disabilities. Children learned to conduct self-assessments and to compare their ratings with those of the teacher. Data were collected on children's percentages of appropriate behavior, the level of teacher prompting, and the match between child and teacher ratings. Results indicated that the treatment produced immediate and substantial improvements in child behavior and that it was possible to systematically withdraw each component while maintaining a high level of appropriate child behavior. PMID- 2332025 TI - Sometimes patent medicine works: a reply to Braaten, Kauffman, Braaten, Polsgrove, and Nelson. PMID- 2332026 TI - Characterization of neuronal cholecystokinin receptor by L-364,718 in Auerbach's plexus. AB - The release of [3H]acetylcholine [( 3H]ACh) from Auerbach's plexus and the contraction of longitudinal muscle strips in response to the administration of cholecystokinin (CCK) were measured and recorded simultaneously. The peripheral CCK receptor antagonist, 3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4 benzodiazepine-3-yl)-1H- indole-2-carboxamide (L-364,718), antagonized the ACh releasing effect of CCK in a dose-dependent manner. The IC50 value and the dissociation constant (KD) were 41.0 +/- 2.0 pM and 0.06 +/- 0.01 nM, respectively. These results suggest that L-364,718 is a very potent antagonist of the neuronal CCK receptors. PMID- 2332027 TI - Inhibitory action of dantrolene on Ca-induced Ca2+ release from sarcoplasmic reticulum in guinea pig skeletal muscle. AB - The effects of dantrolene on the sarcoplasmic reticulum and contractile machinery were examined in skinned skeletal muscles of guinea pigs. Dantrolene inhibited Ca induced Ca2+ release at 38 degrees C. The inhibitory effect of dantrolene on Ca2+ release was greater in the presence of caffeine or adenine nucleotide than in their absence at low Ca2+ concentrations. Dantrolene suppressed the maximum rate of Ca-induced Ca2+ release but did not affect the sensitivity to Ca2+. At 20 degrees C, however, dantrolene did not inhibit Ca2+ release induced by any Ca2+ concentration, regardless of the presence and absence of caffeine, adenine nucleotide or Mg2+. Ca2+ uptake into the sarcoplasmic reticulum and the Ca2+ sensitivity of the contractile machinery were not affected by dantrolene at 38 degrees C and 20 degrees C. These results suggest that dantrolene is a selective inhibitor of the Ca-induced Ca2+ release mechanism at physiological temperatures without having an effect on the Ca2+ pump of the sarcoplasmic reticulum or on the contractile machinery of skeletal muscle. PMID- 2332028 TI - Carbachol-induced potentiation and inhibition of acid secretion by guinea pig gastric gland. AB - The effects of muscarinic ligands on acid secretion were examined by estimating the accumulation of [14C]aminopyrine in gastric glands isolated from guinea pigs. The accumulation of [14C]aminopyrine in the presence of 0.1 mM histamine was potentiated by 1 microM carbachol but suppressed by 1 mM. These two effects of carbachol were abolished by atropine, pirenzepine and AF-DX 116. Assuming that the binding of carbachol to one site (Site 1) increases [14C]aminopyrine accumulation but its binding to the other site (Site 2) reduces [14C]aminopyrine accumulation, we analysed the dose-response curves for the carbachol effects in the absence and presence of different concentrations of atropine, pirenzepine and AF-DX 116. The dissociation constants determined for these ligands at Sites 1 and 2 were as follows: carbachol, 0.28 and 7.1 microM; atropine, 0.28 and 0.54 nM; pirenzepine, 45 and 560 nM; and AF-DX 116, 380 and 4400 nM, respectively. The binding of [3H]N-methylscopolamine to the gastric glands indicated the presence of two populations of binding sites with different affinities for the above ligands, other than atropine. The apparent dissociation constants, which were estimated by analysing the displacement curves for [3H]N-methylscopolamine binding, were as follows: carbachol, 0.18 microM (10%) and 31 microM (90%); atropine, 1.24 nM; pirenzepine, 15 nM (16%) and 220 nM (84%); and AF-DX 116, 370 nM (10%) and 2970 nM (90%). These results suggest that there are two kinds of muscarinic acetylcholine receptors in the guinea pig gastric gland, one potentiating and the other inhibiting the acid secretion induced by histamine. PMID- 2332029 TI - The influence of nifedipine and mioflazine on mitochondrial calcium overload in normoxic and ischaemic guinea-pig hearts. AB - The influence of nifedipine (20 nM) and mioflazine (300 nM), i.e. concentrations inducing a 60-70% recovery of cardiac function during reperfusion of globally ischaemic guinea-pig working hearts, on the mitochondrial calcium content was investigated in normoxic, globally ischaemic and reperfused globally ischaemic guinea-pig working hearts. Mitochondrial calcium was determined electronmicroscopically with oxalate-pyroantimonate method. In normoxic hearts both nifedipine and mioflazine reduced the mitochondrial calcium content. Global ischaemia for 45 min and subsequent reperfusion for 25 min resulted in a pronounced mitochondrial calcium overload and damage to the cellular structure. In ischaemic and in reperfusion hearts the drugs maintained mitochondrial calcium at pre-ischaemic levels and decreased the damage to the cellular structure. PMID- 2332030 TI - The inhibitory influence of tracheal mucosa mounted in close proximity to canine trachealis. AB - Reduced smooth muscle contractile responses to agonists occur in the presence of epithelium, perhaps due to the release of an epithelium-derived relaxing factor (EpDRF). It is not clear whether the release of EpDRF requires the direct attachment of the epithelium to the smooth muscle. In the present study, using isolated canine tracheal smooth muscle strips, we examined whether the inhibitory effects of airway mucosa require the attachment of the mucosa to smooth muscle. The smooth muscle contractile responses to acetylcholine and histamine were reduced in the presence of airway mucosa, whether the mucosa was attached or in close proximity. The inhibitory effect mediated by the airway mucosa therefore is not dependent on mucosal attachment to smooth muscle. This phenomenon appears to be due to the release of a soluble, short-acting mediator from the airway mucosa. PMID- 2332031 TI - Muscarinic suppression of the evoked N-wave by oxotremorine-M recorded in the guinea-pig olfactory cortex slice. AB - The effect of the muscarinic agonist oxotremorine-M has been studied on the surface-negative field potential (N-wave) evoked by orthodromic stimulation of the lateral olfactory tract in slices of guinea-pig olfactory cortex. Bath application of oxotremorine-M (5-80 microM) or carbachol (10-300 microM) produced a reversible depression of the N-wave amplitude without affecting the lateral olfactory tract compound action potential. Oxotremorine-M was approximately 5 times more potent than carbachol in this respect, and the effects of both agonists were competitively blocked by telenzepine (5-100 nM), a selective M1 receptor antagonist. In contrast, methoctramine or AF-DX 116, two 'cardioselective' M2-receptor antagonists, had little or no blocking effect on the agonist responses. It is suggested that oxotremorine-M (like carbachol) inhibits the evoked field potential by activating presynaptic M1-type muscarinic receptors in the olfactory cortex slice. PMID- 2332032 TI - Potent oral anticonvulsant action of CPP and CPPene in DBA/2 mice. AB - CPP (3-(2-carboxypiperazine-4-yl)-1-phosphonate), and its unsaturated analogue, CPPene (3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid), have potent anticonvulsant activity against sound-induced clonic seizures in DBA/2 mice. Following i.p. administration the protection is maximal at 1-2 h, and the ED50 values (mumol/kg) are: D(-)-CPPene, 1.54; D(-)-CPP, 2.75; D,L( +/- )-CPP, 4.36. Following oral administration the protection is maximal at 3-4 h and the ED50 (mumol/kg) values are: D(-)-CPPene, 40.19; D(-)-CPP, 65.80; D,L( +/- )-CPP, 108.1. PMID- 2332033 TI - The morphogenesis of cyclohexylamine-induced testicular atrophy in the rat: in vivo and in vitro studies. AB - Male Wistar strain rats were fed a diet providing an intake of 0 or 400 mg cyclohexylamine (CHA)/kg body weight/day for 1, 3, 7, 9, or 13 weeks. At the end of the appropriate feeding period the rats were perfused-fixed with Karnovsky's fixative. The weights of the fixed testes were recorded and the testes, epididymides, and spermatic cord were sampled and processed into methacrylate resin. Histopathological examination of the testes showed changes after 3 weeks of CHA administration. The most frequent and consistent lesion consisted of a focal, basal vacuolation of the Sertoli cell cytoplasm associated with the local loss of spermatocytes and spermatogonia. After a 7-week administration, the Sertoli cell vacuolation was extensive, while the germ cell population showed mild to moderate degeneration and depletion. After longer periods of treatment the lesion was more severe and affected a greater number of tubules leading to general disruption of the germinal epithelium. Cocultures of Sertoli and germ cells were prepared from the testes of Wistar strain rats and exposed to (CHA) or its metabolite 4-aminocyclohexanol (4ACH) at concentrations ranging from 0.1 to 10 mM for periods of 24-72 hr. The cultures were fixed, stained, and examined by light microscopy. Cultures exposed to CHA or 4ACH showed morphological changes comparable with those seen in vivo. Sertoli cell vacuolation was the earliest change with progressive germ cell degeneration and exfoliation from the Sertoli cell monolayer. At equimolar concentrations, CHA produced more marked changes than 4ACH. These results suggest that CHA itself acts directly on the testis and that its primary cellular target is the Sertoli cell. PMID- 2332034 TI - Reversible mitochondrial swelling in cultured rat hepatocytes exposed to 1,2 dimethylhydrazine. AB - The early structural changes of F344 rat hepatocytes exposed to the hepatocarcinogen 1,2-dimethylhydrazine (DMH) were characterized in short-term monolayer cultures. Continuous exposure of monolayers to DMH (2-16 mM) caused cytoplasmic vacuoles visible by phase-contrast microscopy in all hepatocytes within 6 hr of exposure. These changes preceded maximal release of lactate dehydrogenase (LDH) which occurred after 48 hr of continuous exposure to cytocidal concentrations of DMH (8-16 mM). Ultrastructurally, hepatocytes exposed to DMH (4 mM, 6 hr) showed a twofold increase in mitochondrial diameter from 340 +/- 70 nm in control hepatocytes to 800 +/- 140 nm in DMH-exposed cells. Hepatocyte monolayers exposed to DMH (4 mM, 6 hr) with subsequent removal of DMH attained normal phase-contrast appearance within 6 hr. Ultrastructural studies showed no significant differences when compared with control hepatocytes and mitochondrial diameters (330 +/- 70 nm) were comparable with control hepatocytes. Pretreatment of hepatocytes with depletors of cellular reduced glutathione concentration, including 1,3-bis(2-chloroethyl)-1-nitrosourea (40 microM) and diethyl maleate (160 microM), did not potentiate hepatocellular vacuolation nor release of LDH from hepatocytes exposed to DMH (0-16 mM, 48 hr). These studies demonstrate a distinctive form of reversible high-amplitude mitochondrial swelling that can be monitored by phase-contrast microscopy of cultured hepatocytes in monolayers. Since DMH-induced mitochondrial swelling and its progression to irreversible injury are not potentiated by depletors of reduced thiols, this response appears distinct from prelethal mitochondrial swelling in hepatocytes subjected to oxyradical-mediated mechanisms of injury. PMID- 2332035 TI - Effects of collagen matrix on proliferation and differentiation of vascular smooth muscle cells in vitro. AB - In an attempt to better define the relationship between collagen matrices and vascular smooth muscle cells in vitro, proliferation of smooth muscle cells was observed in the early stages of culture. Cells spread on collagen gels had a longer doubling time and less incorporation of [3H]thymidine into DNA on the first day of culture than did cells grown on a plastic substrate. Cells on collagen gels were more elongated than were those on the plastic substrate and showed a "hills and valleys" arrangement from the first day in culture on the collagen type III gel. All cells were identified as smooth muscle having definite microfilaments, dense bodies, and pinocytotic vesicles. They had a distinct actin filament running from end to end when labeled with nitrobenzoxadiazole phallacidin. Cells on the collagen gels had a larger number of actin filaments traveling parallel to the direction of the major axis of their cytoplasm than did those on the glass substrate. Therefore, cultured smooth muscle cells in the more physiological environment for cells in vitro, i.e., on collagen gels, show a suppression of cellular proliferation and an enhancement of differentiation in the early stages of culture. The effects of collagens on the differentiation of cells vary with the collagen phenotype. PMID- 2332036 TI - In vivo demonstration of enhanced arterial constrictor response to serotonin following focal endothelial cell loss. AB - Arterial sensitivity to vasospasm was assessed prior to and 2 weeks following a 15-min period of external compression of the superficial femoral artery in dogs. Compression was achieved by placing a plastic cuff around the artery to produce a 40-60% reduction in the artery cross-sectional area. An additional six dogs were used to assess morphologic changes produced in the artery immediately and at 2 weeks after compression. Angiography following intraarterial infusions of serotonin (10 and 30 micrograms/min), norepinephrine (0.1 microgram/min), ergonovine (20 micrograms/min), and the thromboxane mimic U-46,619 (0.1 microgram/min) demonstrated a specific sensitivity to serotonin 2 weeks after the 15-min application of external arterial compression. The serotonin response was antagonized by the specific serotonin (5-HT2) receptor antagonist, ketanserin. Scanning electron microscopy of the acutely injured luminal surface revealed loss of endothelium and deposition of platelets. Patchy areas with intact endothelium and migrating leukocytes were located within the denuded sites. Two weeks after constrictor placement, the compressed area appeared as a raised or semiraised lesion in which the orientation and shape of the luminal cells were distinctly delineated from the adjacent noninjured segments. However, the luminal cells appeared to be endothelium that had regrown over the previously denuded area. The results of this study demonstrate, in an in vivo model, an enhancement in serotonin-mediated vasoconstriction following intimal injury and repair and support the suggestion that endothelial damage or dysfunction may play a role in the pathophysiology of arterial spasm. PMID- 2332037 TI - Morphologic characterization of early prostatic carcinomas in the ACI rat: a light and electron microscopic study. AB - The ACI rat constitutes a unique model for human prostatic carcinogenesis. A high percentage of these animals spontaneously develop prostatic carcinomas in the ventral lobe as they age. The light microscopic appearance of these tumors is similar to the cribriform pattern of adenocarcinoma in human prostate. In order to further characterize this useful model, we carried out light and electron microscopy studies of the morphology of carcinomatous lesions developing in these animals. Sixteen rats ranging in age from 25 to 43 months were examined histologically, and ultrastructural studies were performed on eight of these cases. The neoplastic cells showed features of well-developed secretory epithelium including prominent Golgi apparatus, abundant rough endoplasmic reticulum, and numerous secretory vacuoles. Microvilli were numerous in some cells and focal apocrine secretory activity was present. Intraluminal crystals similar to those associated with human prostate carcinoma were observed in one of our cases. Prostate carcinomas developing in the ACI rat share many of the ultrastructural features of human prostatic carcinoma. PMID- 2332038 TI - Intracellular distribution of gentamicin within the rat kidney cortex: a cell fractionation study. AB - The present study demonstrates that during the first 1.5-3 min after a single intraperitoneal administration of [3H]gentamicin to rats, most of the radioactivity in the kidney cortex is recovered in the cytosolic and microsomal fractions upon subcellular fractionation. Subsequently, the level of radioactivity recovered in the cytosolic fraction decreases markedly, whereas this level remains relatively unchanged in microsomes and increases somewhat in the nuclear and mitochondrial fractions. A steady state is apparently reached 13 hr after the injection. The high initial concentration of gentamicin in the cytosol may indicate that this substance is taken up to a large extent by diffusion. Such uptake is somewhat surprising, because of the polar nature of gentamicin. The small size of this drug may, however, allow it to diffuse through so-called pores and/or interaction with negatively charged phospholipids may be involved in the uptake of gentamicin. The initial total level of radioactivity recovered in microsomes after in vivo administration of [3H]gentamicin was considerably higher than in the nuclear and mitochondrial-lysosomal fractions. Furthermore, when gentamicin was added directly to kidney homogenate prepared from untreated rats, instead of being administered in vivo, this substance was still recovered in highest amounts in the total microsomal fraction. This observation may indicate that enrichment of gentamicin in the endoplasmic reticulum (or fragments thereof) reflects a special affinity of this drug for these membranes and is probably not the result of a particular in vivo process. There was no difference in the levels of radioactivity recovered in smooth and rough microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332039 TI - Prognostic significance of secondary cytogenetic changes and nonspecific cross reacting antigen (NCA) in patients with Ph-positive chronic myeloid leukemia. AB - Cytogenetic analyses were carried out on peripheral blood and bone marrow cells of 31 chronic myeloid leukemia (CML) patients who presented with blastic, accelerated, or chronic phases. The percentage of cytoplasmic nonspecific cross reacting antigen (cNCA, a marker of myelocytic differentiation)-containing cells was determined in the same blood or bone marrow samples. The patients were divided in two groups according to cytogenetic results: those with aberrations in addition to the Philadelphia chromosome (Ph1) and those with Ph1 only. Among the additional aberrations such changes, not typical of CML, were found: del(2)(p21), t(6;11)(q25;q23), and t(12;?)(p13;?). The survival time and the percentage of cNCA-positive cells of patients in blastic and accelerated phases were compared between the above-mentioned two groups of patients using the Student t test and the Kaplan-Meier estimator. The percentage of cNCA-positive cells was significantly lower and the survival time significantly shorter in the group of patients with additional aberrations. The probability of survival according to the Kaplan-Meier estimator was also lower for this group. These data suggest that the immunologically determined lower degree of maturity, that characterized cells bearing additional aberrations, coincides with and/or results in more rapid progression of the disease. PMID- 2332040 TI - Effect of Plasmodium yoelii infection on GABA metabolism of mouse brain. AB - Plasmodium yoelii infection in albino mice decreased the activity of brain glutamic acid decarboxylase (GAD) by about 30 and 48% in crude homogenate and its synaptosomal fraction, respectively. The decrease was evident from 20% parasitemia and remained more or less constant up to 80% parasitemia. The Km values of GAD in normal and infected animals were 1.2 x 10(-2) and 3.3 x 10(-2) mM, respectively, indicating a decrease in enzyme substrate affinity due to infection. The lowered GAD activity rose to slightly above normal by treatment of infected animals with chloroquine. Decrease in GAD activity reflected lower gamma aminobutyric acid (GABA) levels in the infected brain; however, GABA-transaminase activity was not significantly influenced by infection. It has been proposed that impaired GABA synthesis may be due to hypoxia induced by malarial infection. PMID- 2332041 TI - Quantitative ultrastructural analysis of hepatoprotective effects of (+) cyanidanol-3 on alcoholic liver damage. AB - Biochemical considerations suggest that bioflavonoids may be effective antihepatotoxic and hepatoprotective agents. We, therefore, designed a morphometric study to examine the effect of (+)-cyanidanol-3 on ethanol-induced hepatocellular alterations. Using a stereologic point and intersection counting method we determined the volume fraction of cytoplasmic components, the surface area of cytoplasmic membranes, some parameters of mitochondria, and numerical densities of some organelles, after chronic ethanol intoxication and hepato protective treatment of rats. Consistent with previous qualitative and quantitative descriptions, chronic ethanol feeding caused increases in parameters of mitochondria, microsome, and Golgi complex. The hepatoprotective (+) cyanidanol-3 treatment restored most of the morphologic distortion caused by ethanol ingestion. The (+)-cyanidanol-3 treatment alone caused an elevation of the surface area of smooth endoplasmic reticulum and nonsignificant changes in mitochondrial parameters, possibly due to its inducing effect on microsomes and activating effect on mitochondrial enzymes. These data indicate that bioflavonoids could be of potential benefit in hepatotoxic or alcohol-related liver disease. PMID- 2332042 TI - Interleukin 1 beta modulates hepatic synthesis of alpha 1-acid glycoprotein in the fetal rat. AB - The ability of the fetal rat to respond to interleukin 1 beta (IL1 beta) by expressing alpha 1-acid glycoprotein (AGP) was investigated. Eight and 20 h after injection of 7 ng IL1 beta into 19-day fetuses, liver AGP mRNA increased by a factor of 66 and 82 respectively, while serum AGP levels increased by a factor of 3 and 5. Similar treatment of the mothers altered in the fetuses neither AGP serum levels nor the amount of liver AGP mRNA. The induction of AGP gene expression in the fetal liver in response to IL1 beta was similar to that observed in the adult liver. These results demonstrate that at day 19 the fetal rat liver has acquired a mature acute-phase system. PMID- 2332043 TI - Assignment of imidazole resonances from two-dimensional proton NMR spectra of bovine Cu,Zn superoxide dismutase. Evidence for similar active site conformation in the oxidized and reduced enzyme. AB - Two-dimensional 1H-NMR spectra were carried out on bovine Cu(I),Zn superoxide dismutase. The ring protons of the single tyrosine and of the 4 phenylalanines were identified from COSY spectra. From NOESY spectra all imidazole C-resonances could be specifically assigned to each of the 8 histidines using the crystal coordinates of the Cu(II),Zn enzyme. Since 6 histidines are involved in the structure of the active site, this result implies nearly identical active site conformations for the two oxidation states of the catalytic cycle of this enzyme, in line with its diffusion-limited rate. PMID- 2332044 TI - The importance of Val-157 hydrophobic interaction for papain inhibitory activity of an epoxysuccinyl amino acid derivative. A structure-activity relationship based on the crystal structure of the papain-E-64-c complex. AB - Based on the crystal structure of the papain-E-64-c complex, 3-dimensional binding modes of a series of epoxysuccinyl amino acid derivatives to the papain active site have been constructed and the structure-inhibitory activity relationship has been analyzed using the accessible surface area and nonbonded energy parameters. The result indicates the importance of the hydrophobic interaction between the amino acid side chain of the inhibitor and the papain Val 157 residue for revealing the potent inhibitory activity. PMID- 2332045 TI - Autolysis of isolated adipocytes by endogenously produced fatty acids. AB - Isolated rat adipocytes, in which lipolysis was maximally stimulated by isoproterenol, continued to produce fatty acids in excess of the high-affinity binding capacity of the fatty acid acceptor bovine serum albumin in the incubation medium. At an average of 17 mol fatty acids/mol serum albumin, there was a burst of lactate dehydrogenase activity recovered in the incubation medium, indicating cell lysis. It is concluded that endogenously produced fatty acids will cause autolysis of adipocytes in vitro. Actively lipolysing adipocytes were more fragile than resting cells, since increasing amounts of lactate dehydrogenase activity was recovered in the medium during active lipolysis. PMID- 2332046 TI - Regional expression of a MCD-peptide and dendrotoxin I-sensitive voltage dependent potassium channel in rat brain. AB - In situ hybridization histochemistry has been used to analyze the regional expression of a class of voltage-dependent K+ channel that is sensitive to two polypeptide toxins (MCD peptide and dendrotoxin I) that produce spectacular effects on brain function. A heterogeneous expression of this K+ channel was observed throughout the brain. High mRNA contents were observed in the granule cells of the gyrus dentatus as well as in pyramidal cells of the Ammon horn (CA3 greater than CA1) and in the cerebellum. Conversely, low levels of expression were found in basal ganglia (caudate putamen, globus pallidus, and ventral pallidum). PMID- 2332047 TI - The interaction of amiloride with acetylcholinesterase and butyrylcholinesterase. AB - The diuretic drug amiloride was found to be a powerful inhibitor of the reaction of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with their specific choline ester substrates. The inhibition constant is in the micromolar range. On the other hand, when added to a mixture of cholinesterase (AChE and BChE) and neutral substrates, amiloride, in some cases, enhanced the reaction rate. The rate of the reaction of butyrylcholinesterase with p-nitrophenyl butyrate was increased up to 12 fold by amiloride. PMID- 2332048 TI - Substrate-dependent inhibition of protein kinase C by specific inhibitors. AB - Protein kinase C (PKC) and its proteolysis-derived protein kinase independent of Ca2+ and phospholipids (PKM), were purified from rat brain. By using histone H1 and protamine as substrates, we assayed the effect of several inhibitors of PKC and PKM. The inhibition turned out to be dependent on both the nature of the kinase and the type of substrate assayed. These results may help to interpret the different responses elicited by PKC inhibitors in vivo. PMID- 2332049 TI - Benzo(a)pyrene induces nuclear-DNA adducts in plant cell suspension culture. Detection by [32P] postlabelling. PMID- 2332050 TI - Protein kinase C during differentiation of human promyelocytic leukemia cell line, HL-60. AB - Protein kinase C (PKC) from human promyelocytic leukemia HL-60 cells can be resolved into three fractions (peak, a, b and c) by hydroxyapatite column chromatography. Peak a and c enzymes are indistinguishable from the brain type II PKC having beta (beta I and beta II)-sequence and type III having alpha-sequence, respectively. Peak b enzyme is a previously unidentified PKC subspecies that has enzymological properties subtly different from type I (having gamma-sequence), type II and type III PKC. Upon treatment of HL-60 cells with 1 microM retinoic acid, this peak b enzyme is decreased dramatically within 24 h, whilst peak a enzyme (beta-PKC) is increased, and peak c (alpha-PKC) enzyme is slightly decreased within 48 h. The result implies that the PKC subspecies in HL-60 cells have distinct functions during cell differentiation. PMID- 2332051 TI - The in vivo and in vitro oxidation of molecular form 1 of biliverdin reductase to molecular form 3 by diamide. AB - Administration of phenylhydrazine to rats converted molecular form 1 of the liver biliverdin reductase into its disulfide bridged dimer (molecular form 3). This oxidative dimerization was shown not to be mediated by the NAD(+)-dependent dehydrogenase [(1984) Biochem. Biophys. Res. Commun. 121, 249-254]. Administration of diamide produced the same conversion. Although hepatic levels of GSH also decreased, no mixed disulfides of the reductase and GSH could be detected. Administration of the antioxidants allopurinol and alpha-tocopherol together with the diamide did not affect this conversion of molecular forms produced by the latter. The diamide also oxidized molecular form 1 of biliverdin reductase in vitro and molecular form 3 was formed. The chemical oxidation took place at a high rate and was partially inhibited by GSH but not by cysteine. PMID- 2332052 TI - C-terminal amino acid determination of the transmembrane subunits of the human platelet fibrinogen receptor, the GPIIb/IIIa complex. AB - Glycoproteins IIb (GPIIb) and IIIa (GPIIIa) form the Ca2(+)-dependent GPIIb/IIIa complex, which acts as the fibrinogen receptor on activated platelets. GPIIb and GPIIIa are synthesized as single peptide chains. The GPIIb precursor is processed proteolytically to yield two disulphide-bonded chains, GPIIb alpha and GPIIb beta. The GPIIb/IIIa complex has two membrane attachment sites located at the C termini of GPIIb beta and GPIIIa. The short cytoplasmic tails of GPIIb beta and/or GPIIIa become most likely associated to the cytoskeleton of activated platelets. In the present work the C-terminal amino acid residues of platelet GPIIb beta and GPIIIa have been analyzed by protein-chemical methods and compared with those predicted from cDNA analysis. We were able to confirm the positions of the C-termini in both glycoproteins and the identity of the C-terminus predicted for GPIIIa, i.e. threonine. However, glutamine, not glutamic acid as predicted for GPIIb beta from the human erythroleukemic cell line and megakaryocyte cells, was found to be the C-terminal amino acid of GPIIb beta. This indicates that the glutamic acid in the GPIIb precursor is posttranslationally modified to glutamine. PMID- 2332053 TI - Tetanus toxin-induced protein kinase C activation and elevated serotonin levels in the perinatal rat brain. AB - A single intracerebral injection of tetanus toxin (TeTox) is able to produce a time-dependent translocation of Ca2(+)-phosphatidylserine-dependent protein kinase C (PKC) in close-to-term rat brain. TeTox-triggered translocation of PKC is dose- and time-dependent, can be prevented by tetanus antitoxin, and does not occur upon administration of toxin fragments B and C. TeTox-triggered PKC translocation is accompanied by a time-dependent increase in brain serotonin (5 HT). Increase of brain 5-HT is independent of monoamine oxidase inhibition by pargyline. Phorbol ester and TeTox cause a significant increase in serotonin while H-7, a kinase inhibitor, does not affect serotonin levels but abolishes the effect of TeTox. Gangliosides prevent TeTox-triggered 5-HT increase. The data are consistent with the possibility that TeTox acts effectively on the serotonergic innervation, presumably in conjunction with PKC to cause accumulation of serotonin. PMID- 2332054 TI - Reversible inhibition of electron transfer in the ubiquinol. Cytochrome c reductase segment of the mitochondrial respiratory chain in hibernating ground squirrels. AB - Electron transfer through the ubiquinol:cytochrome c1-segment of liver mitochondria isolated from hibernating ground squirrels Citellus undulatus is repressed by 70-80% as compared to mitochondria from the active animals. The inhibition site is likely to be localized between ubiquinone and the cytochrome bc1 complex. Partial release of the inhibition can be observed upon swelling of the isolated mitochondria in a hypoosmotic medium, the effect being prevented by phospholipase A2 inhibitors. Possible role of phospholipase A2 in regulation of ubiquinol oxidation by complex bc1 is discussed. PMID- 2332055 TI - The primary structure of rat ribosomal protein S16. AB - The amino acid sequence of rat ribosomal protein S16 was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed from the NH2-terminal amino acid sequence of the protein. S16 contains 145 amino acids (the NH2 terminal methionine is removed after translation of the mRNA) and has a molecular mass of 16,304. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 11-13 copies of the S16 gene. The mRNA for the protein is about 700 nucleotides in length. Rat S16 is homologous to mouse S16 (there are 2 amino acid changes and a residue is deleted) and related to Halobacterium morismortui ribosomal protein S3 and to Escherichia coli S9. PMID- 2332056 TI - Stereochemical course of hydrolysis and hydration reactions catalysed by cellobiohydrolases I and II from Trichoderma reesei. AB - Cellobiohydrolase I from Trichoderma reesei catalyzes the hydrolysis of methyl beta-D-cellotrioside (Km = 48 microM, kcat = 0.7 min-1) with release of the beta cellobiose (retention of configuration). The same enzyme catalyzes the trans hydration of cellobial (Km = 116 microM, kcat = 1.16 min-1) and lactal (Km = 135 microM, kcat = 1.35 min-1), presumably with glycosyl oxo-carbonium ion mediation. Protonation of the double bond is from the direction opposite that assumed for methyl beta-cellotrioside, but products formed from these prochiral substrates are again of beta configuration. Cellobiohydrolase II from the same microorganism hydrolyzes methyl beta-D-cellotetraoside (Km = 4 microM, kcat = 112 min-1) with inversion of configuration to produce alpha-cellobiose. The other reaction product, methyl beta-cellobioside, is in turn partly hydrolysed by cellobiohydrolase II to form methyl beta-D-glucoside and D-glucose, presumably the alpha-anomer. Reaction with cellobial is too slow to permit unequivocal determination of product configuration, but clear evidence is obtained that protonation occurs from the si-direction, again opposite that assumed for protonating glycosidic substrates. These results add substantially to the growing evidence that individual glycosidases create the anomeric configuration of their reaction products by means that are independent of substrate configuration. PMID- 2332057 TI - Cryopreservation and its problems. PMID- 2332058 TI - Influence of superovulation on endometrial and embryonic development. AB - The authors have studied the temporal relationship between follicular rupture and endometrial development in 13 women during a natural ovarian cycle (length 25 to 35 days), and subsequently after standard treatment with clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin (hCG) to induce multiple folliculogenesis for oocyte recovery, in vitro fertilization, and embryo freezing (cycle length 23 to 27 days). An endometrial biopsy was taken during both cycles 1.5 to 2.0 days after the oocytes had been released or removed. The samples were examined by light and transmission electron microscopy. Samples of peripheral blood were taken at defined times for hormone analysis. After treatment 11 subjects (85%) had advanced morphological development of the endometrium (8 women by 3 to 4 days, 3 women by 1 to 2 days). The concentrations of plasma estradiol (E2) and progesterone (P) on the days of follicular rupture and endometrial biopsy were significantly raised in the treatment cycles. The concentration of total urinary estrogens on the day of hCG administration and the mean change in the concentration of plasma E2 (treatment/control) on the days of endometrial biopsy were positively correlated with the extent of endometrial advancement. In addition, the mean change in the concentration of plasma P (treatment/control) was markedly increased on the days of follicular rupture and endometrial biopsy in those subjects with an advanced endometrium. Embryonic development was not so obviously related to the extent of superovulation. Asynchronous endometrial and embryonic development may therefore contribute to the low pregnancy rate in these patients. PMID- 2332059 TI - Endometrial synthesis and secretion of complement component-3 by patients with and without endometriosis. AB - In the present study we examined complement-3 (C3) synthesis and secretion from early proliferative endometrium of infertile patients with and without endometriosis. One gram of tissue was obtained by endometrial sampling at the time of diagnostic laparoscopy and incubated for 12 to 16 hours in the presence of radioactive methionine. Immunoprecipitation was performed with rabbit antihuman C3 immunoglobulin G and only a single 180-kDa radiolabeled protein (C3) was immunoprecipitated. This protein dissociates into 113- and 69-kDa subunits in the presence of dithiothreitol. The amount of C3 produced and secreted by the endometrium was quantitated as a percentage of counts per minute recovered by immunoprecipitation. Patients with minimal endometriosis produced significantly greater amounts of endometrial C3 than patients with no endometriosis or patients with severe endometriosis. PMID- 2332060 TI - Identification of low molecular weight immunosuppressor molecules in human in vitro fertilization supernatants predictive of implantation as a polyamine- possibly spermine. AB - Suppressor activity in in vitro fertilization (IVF) culture medium correlates with successful implantation. High performance liquid chromatography fractionation revealed peak(s) of inhibitory activity in the 1,000- to 5,000-Da molecular weight range. Inhibitory activity was dependent on the presence of fetal bovine serum (FBS) and was abrogated both by heat treatment of the serum and by pretreatment with monoamine oxidase inhibitors. Spermine becomes toxic when oxidized by monoamine oxidase to spermine dialdehyde or acrolein. Spermine also shows suppressive activity in the same molecular weight range as IVF supernatants. These data suggest IVF-associated inhibitory activity may be attributable to oxidation of a polyamine, possibly spermine, by monoamine oxidase in FBS. The biological significance is discussed. PMID- 2332061 TI - The influence of chamber characteristics on the reliability of sperm concentration and movement measurements obtained by manual and videomicrographic analysis. AB - To assess the influence of chamber design and depth on the accuracy and precision of sperm measurements, manual counting of a standardized latex bead solution and automated sperm motility measurements were made using a Makler chamber (Sefi Medical Industries, Haifa, Israel), Neubauer hemocytometer (American Optical Company, Buffalo, NY), and a new, disposable device (Micro-Cell; Cyto Fluidics, Inc., Silver Spring, MD). Bead counts obtained with the Micro-Cell chamber or hemocytometer were not statistically different from those determined by electronic particle counting, whereas Makler chamber counts were 62% higher. Makler counts had a significantly higher standard deviation, suggesting that counts made with this device are less reproducible. Analyzing live sperm samples, the percentage of motile sperm determined using Micro-Cell and Makler chambers were similar. However, significant differences in sperm concentration and mean velocity were found. The Micro-Cell disposable chamber provided consistent and accurate data on sperm concentration, percent motility, and mean velocity. These differences in sperm measurements emphasize the importance of sampling chamber characteristics on data reliability. PMID- 2332062 TI - Characterization of humoral antibodies reactive with spermatozoa, N-acetyl galactosamine, and a putative blood group antigen in seminal plasma. AB - Antisperm antibodies in sera of infertile women may react differently with spermatozoa of different men. We studied the reactivity of these antibodies with spermatozoa from men of varying blood group status. Increased immunoglobulin binding to sperm of group A or AB men was noted when compared with group O men. A diminution in binding of immunoglobulins to spermatozoa after absorption of these sera with human group A or AB red blood cells was noted as well as after coincubation of sera and sperm with N-acetyl galactosamine, the terminal sugar of blood group antigen A. These observations suggest that antibodies directed against blood group antigens adsorbed to sperm of secretor males may account in part for variations in immunobead binding levels between sperm of different men. PMID- 2332063 TI - The efficacy of cryopreserved hamster ova in the sperm penetration assay. AB - To solve the logistical problems of the sperm penetration assay (SPA) to provide just a sufficient number of hamster ova exactly when they are needed, a new method to cryopreserve the ova has been devised. The ova, suspended in a 1.5 M solution of propylene glycol as a cryoprotectant in an isotonic salt solution, were frozen in 1/4 mL plastic straws. Included in each straw was a sucrose solution, isosmotic to the propylene glycol solution, to serve as an osmotic buffer during dilution of the cryoprotectant out of the ova. This one-step method of dilution permitted the ova to be recovered and diluted out of the cryoprotectant within the straw in which they had been originally frozen. A total of 547 cryopreserved ova were thawed, 504 (92.1%) of which were morphologically normal after they had been incubated at 37 degrees C for 3 hours. After removal of the zonae, the frozen-thawed ova were compared with fresh, control ova in SPAs of donor and patient semen that had been capacitated in TEST-yolk buffer. The percent penetration and penetration index of fresh versus cryopreserved ova did not differ significantly for either donor or patient semen. PMID- 2332064 TI - The rat as an animal model for endometriosis to examine recurrence of ectopic endometrial tissue after regression. AB - The effects of pregnancy and ovariectomy on the growth of endometrial implants were examined in rats with experimentally induced endometriosis. Ectopic implants regressed completely after ovariectomy and we were unable to detect any viable endometrial cells in histological examination of the implant sites. Administration of 17 beta-estradiol cypionate to ovariectomized rats with regressed endometrial implants led to recurrence of the regressed implants. Animals with experimentally induced endometriosis were fertile and the number of embryos on day 10 of pregnancy was not different from the control group. Ectopic implants which regressed during pregnancy recurred 1 month after parturition. It is concluded that endometrial cells may survive at the implanted site even after apparent complete morphological regression, which has the potential to grow into an implant. PMID- 2332065 TI - Peritoneal fluid from endometriosis patients affects reproductive outcome in an in vivo model. AB - The cause and importance of endometriosis-associated subfertility are a subject of dispute in reproductive endocrinology. To further study this phenomenon, we have established a model to test the effect of peritoneal fluid (PF) from endometriosis patients on early reproductive events in vivo. Sexually mature female golden hamsters were subjected to an ovarian hyperstimulation protocol and divided into groups that received the following intraperitoneal injections: (1) saline, (2) human serum albumin (HSA), (3) PF from fertile controls, and (4) PF from stage I/II endometriosis patients. Animals were killed on days 4 and 17; reproductive performance was assessed by the number of oocytes and embryos recovered on day 4 and the number of uterine swellings counted on day 17. Reproductive performance was significantly impaired by PF from endometriosis patients; animals treated with control PF and HSA did not differ from control. These data demonstrate a marked impairment of early in vivo reproductive performance under the influence of endometriosis PF. These results support a role for a soluble PF component as a mediator in the pathogenesis of endometriosis associated subfertility. PMID- 2332066 TI - Endometrial antibodies in serum and peritoneal fluid of infertile patients with and without endometriosis. AB - Passive hemagglutination assay was used to evaluate endometrial antibodies in serum and peritoneal fluid of 37 patients with endometriosis and 54 patients without endometriosis. The results showed that the concentration of antibody titers in serum and peritoneal fluid was significantly higher for endometriosis than control patients. The severity of endometriosis has no effect on antibody concentration. Furthermore, the concentration of endometrial antibody titers was significantly higher in serum than peritoneal fluid of patients with endometriosis. These results suggest that serum endometrial antibody assay is specific and valuable for the diagnosis and progress of endometriosis. PMID- 2332067 TI - Force generated by human sperm correlated to velocity and determined using a laser generated optical trap. AB - The development of the single beam gradient force optical trap has made it possible to manipulate cells solely by laser light. A continuous wave Nd:YAG (1.06 microns) laser beam was directed into a conventional microscope and focused onto the viewing plane by the objective lens. The laser beam power at which human sperm were released from the trap was measured and correlated to the sperm's linear velocity before trapping. The mean trapping power readings for slow, medium, and fast motile sperm were 57, 73, and 84 mW, respectively. The analysis of measurements over the total population demonstrated that zig-zag motile sperm had significantly higher mean power readings when compared with straight motile sperm with similar mean linear velocities. In two cases, specimens required significantly less trapping power when the measurements were repeated 24 hours later. PMID- 2332068 TI - Congenital aplasia of seminal vesicles: absence of trophoblast-lymphocyte cross reactive antigens from seminal plasma. AB - Our studies show that TLX antigens are absent from seminal plasma of a patient with bilateral aplasia of seminal vesicles. This is supportive for an origin of seminal plasma TLX antigens from seminal vesicles. The release of TLX antigens by seminal vesicles could represent a mechanism of priming mothers immunologically for normal implantation and pregnancy. PMID- 2332069 TI - Gedankenexperiments. PMID- 2332070 TI - Culture media for in vitro fertilization. PMID- 2332071 TI - Oocyte karyotyping. PMID- 2332072 TI - On becoming drug-free: the individual nurse can make a difference. PMID- 2332073 TI - How managers can help the recovering nurse return to work. PMID- 2332075 TI - Do you let stinking thinking get you down? PMID- 2332074 TI - More on co-dependency. PMID- 2332076 TI - McCulloch directs project on nursing assistants. PMID- 2332077 TI - Lay-midwifery bills get reaction from nurses. PMID- 2332078 TI - Ann Lewis addresses nurses at P.A.D. PMID- 2332079 TI - [Comprehensive approach to clinical background and effect of bromocriptine administration in patients with endocrinological polycystic ovarian disease]. AB - Present study was performed to elucidate the clinical features and the treatment of so-called endocrinological polycystic ovarian disease (PCO). 36 cases out of 189 infertile patients who had various ovulatory disturbances were subjected during past four years. They were selected by the definitions as follows; 1) serum LH levels greater than or equal to 30 mIU/ml and serum FSH levels less than or equal to 15 mIU/ml, 2) hyper-response of LH secretion by LH-RH (100 micrograms) loading test; maximum values greater than or equal to 250 mIU/ml. Serum androstenedione (ASD), dehydroepiandrosterone-sulfate (DHA-S), estrone (E1), estradiol (E2), progesterone (P, in the mid-luteal phase) and testosterone (T) levels were examined by RIA method for the purpose of the evaluation of the endocrinological background of the PCO in Japanese women. The same examinations were also done in 8 volunteer women who had normal ovulatory menstrual cycles for the control study. In 6 cases of the PCO patients who showed biphasic BBT charts, the endometrial biopsy was done in the mid-luteal phase at the same time of the blood sampling. And the correlation between various serum hormone levels and the endometrial morphology in the PCO patients was also discussed. Then bromocriptine (5 mg/day) was administered in these patients for more than 30 days and the effect of the treatment was investigated. Serum ASD levels in the PCO patients were significantly higher than those in the control (2.52 +/- 1.30 vs. 1.43 +/- 1.21 ng/ml, M +/- S.D., p less than 0.05), while serum E2 and P levels in the patients were significantly lower than those in the control (E2: 118.6 +/- 39.5 vs. 192.5 +/- 53.9 pg/ml, p less than 0.005. P: 7.26 +/- 5.08 vs. 124.4 +/- 4.6 ng/ml, p less than 0.005, respectively). There were no significant differences in serum levels of the other hormones. By the administration of bromocriptine, serum ASD levels decreased (1.62 +/- 1.34 ng/ml, p less than 0.05), and E2 (177.9 +/- 48.6 pg/ml, p less than 0.025) and P (11.8 +/- 4.3 ng/ml, p less than 0.005) levels increased significantly into the levels of control. Serum LH levels of the patients were also suppressed by the treatment of bromocriptine (42.5 +/- 13.7 vs. 27.4 +/- 12.0 mIU/ml, p less than 0.005), however there was no change in serum FSH levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2332080 TI - [Measurement of plasma free cortisol, estradiol, testosterone and prednisolone by direct radioimmunoassay of ultrafiltrate and its clinical application]. AB - The authors aimed at developing a simplified method for the measurement of plasma free (unbound) steroids with ultrafiltration using Grace MPS device, and its clinical application. In this method, the movement of free steroids from plasma into ultrafiltrate was monitored with [14C]glucose added to the plasma. Plasma free steroids (cortisol, testosterone, estradiol and prednisolone) were measured as follows: Plasma was incubated with [14C]glucose (1.2 X 10(4) dpm/5 microliters) for 30 min at 37 degrees C. A 0.5 ml of aliquot was transferred to MPS device containing a single YMT membrane, and centrifuged at 1100 x g, at 37 degrees C, for 30 min in a 45 degree fixed angle head with the special temperature controller. After centrifugation, [14C] in 30 microliters of plasma and ultrafiltrate were counted. For the calculation of plasma free level, steroid concentration of ultrafiltrate measured directly by radioimmunoassay (RIA) was multiplied by the ratio of [14C]glucose (dpm) in plasma to [14C]glucose (dpm) in ultrafiltrate. For RIA of cortisol, testosterone and estradiol, commercially available kits were used, and for prednisolone, anti-prednisolone antibody developed in our laboratory was utilized. Since plasma free cortisol level showed a parallel increase with rise in temperature, strict temperature control during ultracentrifugation was required. On the other hand, the duration of centrifugation and the sample volume applied to MPS did not show any significant effect on the estimated values. Intraassay and interassay variations were 4.4% and 6.1% in free cortisol, 6.3% and 8.7% in free testosterone, 8.5% and 9.2% in free estradiol, and 8.8% and 9.9% in free prednisolone, respectively. The correlations between the plasma free steroid levels obtained by ultrafiltration (y) and equilibrium dialysis (x) were as follows, respectively: free cortisol; y = 1.16x + 0.017 (r = 0.95, n = 10), free testosterone; y = 1.17x-0.027 (r = 0.92, n = 10), free estradiol; y = 1.33x + 8.55 (r = 0.98, n = 12), free prednisolone; y = 1.03x + 1.00 (r = 0.98, n = 7). The mean plasma free cortisol levels and percent free fractions (%FF) were 1.16 +/- 0.40 (+/- SD) micrograms/dl and 10.9 +/- 3.0% in 10 control patients, 4.4 +/- 1.6 micrograms/dl and 15.6 +/- 3.3% in 8 patients with Cushing's syndrome, and 1.45 +/- 0.48 micrograms/dl and 5.9 +/- 2.4% in 11 normal pregnant women (10-40 weeks of pregnancy), respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2332081 TI - [A case of recessive dystrophic epidermolysis bullosa associated with dwarfism with special reference to pathophysiological role of growth hormone]. AB - Epidermolysis bullosa is a group of disorders whose common primary feature is the formation of blisters following trivial trauma. Recessive dystrophic epidermolysis bullosa (RDEB), a subtype of epidermolysis bullosa, is frequently associated with growth retardation. This growth retardation has been reported to be caused by trophopathy following protein loss through skin lesions. Endocrine disorders as the cause of growth retardation in RDEB have not been clearly described. An 11-year-old female had a typical RDEB with dwarfism. Her height was 125 cm and weight was 21 kg, both of which were 2.5 SD below the average. The skin lesions were generalized and probably caused by undernourishment, infection, and blood loss through the skin. However, her serum albumin was at the lower normal limit, and the rapid turnover proteins were slightly decreased. Endocrinological examinations revealed that all the basal levels of pituitary, thyroid, and adrenal hormones were normal. Results of the exercise test, the insulin tolerance test, and the growth hormone-releasing factor test indicated the presence of hypothalamic disorder in secretion of growth hormone. This is the first report of RDEB in which hypothalamic disorder in growth hormone secretion was investigated. On the other hand, growth hormone is known to be involved in collagen metabolism, and a decrease in collagen fibrils and an increase in collagenase activities are found in the skin of RDEB. This implies that this hypothalamic disorder in growth hormone secretion may be involved in the pathophysiology of both dwarfism and the skin lesions in RDEB. PMID- 2332082 TI - Hypercalcemia and weight loss in a middle-aged female. PMID- 2332083 TI - Influenza. PMID- 2332084 TI - DIMER. PMID- 2332085 TI - The biodemography of variation in human frailty. AB - A population is composed of individuals who are heterogeneous in their susceptibility to death and disease. This heterogeneity is reflected in the age specific incidence or mortality (hazard) function. This variation has typically been hidden--that is, not measured directly--and has generally been modeled in a purely empirical statistical way, because there is no theory in demography for the distribution of frailty. A substantial fraction of variation in frailty, however, has an underlying genetic basis, for which there is a formal theory. This theory, based on evolutionary biology and on the nature of mendelian transmission, provides prior constraints on the distribution of variation in the population as well as providing methods for identifying genes involved in many important diseases. The accumulating effects of environmental exposures with age are another major component of variation in frailty. In some important instances, this variation and its effect on the age-specific hazard function can also be understood in terms of cause-specific biological processes. These biological considerations may enable demographers to model frailty, and thus mortality, in a better way. PMID- 2332086 TI - Factors in the resolution of adolescent premarital pregnancies. AB - This article examines the effect of family background factors on first premarital pregnancy resolution for adolescents in the United States. Teenage fertility constitutes a sizable percentage of total fertility, and each outcome has a potentially different type of family structure associated with it. Not only are there marked racial/ethnic differences in the ways such pregnancies are resolved, but the effects of family structure, age at first conception, family size, and working mother also differ between blacks, whites, and Hispanics. Parental education is a highly significant predictor for all groups: the higher the level of education, the less likely the pregnancy will be carried to term. PMID- 2332087 TI - Household headship among unmarried persons in the United States, 1970-1985. AB - Recent trends in rates of household headship and headship differentials by sex and color are examined within the context of a model that expresses the likelihood of heading an independent household as a function of age, marital status, parental status, and individual money income. The parameters of this model are consistent with predictions derived from a "life-course" perspective and are stable across period, sex, and color. Nonetheless, residual effects of period, sex, and color persist even after the independent variables are taken into account. PMID- 2332088 TI - Mortality differentials by marital status: an international comparison. AB - Although the greater longevity of married people as compared with unmarried persons has been demonstrated repeatedly, there have been very few studies of a comparative nature. We use log-linear rate models to analyze marital-status specific death rates for a large number of developed countries. The results indicate that divorced persons, especially divorced men, have the highest death rates among the unmarried groups of the respective genders; the excess mortality of unmarried persons relative to the married has been generally increasing over the past two to three decades; and divorced and widowed persons in their twenties and thirties have particularly high risks of dying, relative to married persons of the same age. In addition, the analysis suggests that a selection process is operating with regard to single and divorced persons: the smaller the proportion of persons who never marry or who are divorced, the higher the resulting death rates. PMID- 2332089 TI - Birth intervals and childhood mortality in rural Bangladesh. AB - This study investigates the relationship between birth intervals and childhood mortality, using longitudinal data from rural Bangladesh known to be of exceptional accuracy and completeness. Results demonstrate significant but very distinctive effects of the previous and subsequent birth intervals on mortality, with the former concentrated in the neonatal period and the latter during early childhood. The impact of short birth intervals on mortality, however, is substantially less than that found in many previous studies of this issue, particularly for the previous birth interval. The findings are discussed in terms of the potential for family planning programs to contribute to improved child survival in settings such as Bangladesh. PMID- 2332090 TI - Racial and ethnic differences in U.S. census omission rates. AB - This article assesses differences in rates of omission across seven race ethnicity groups in the 1980 census to learn more about the social factors that condition census enumeration. Findings indicate that there are multiple sources of error, that these sources reflect distinctive ethnic attributes to a greater degree than shared minority status, and that census omissions have both inadvertent and motivational causes. The discussion notes some of the implications for improving coverage in future censuses. PMID- 2332091 TI - Estimating the national high school dropout rate. AB - Recent interest has focused on the high school dropout rate as one indicator of the national education picture. Empirical estimates of this "rate" vary considerably, because these estimates are poorly defined. This article reviews some of the current measures and presents a new measure of the high school dropout rate--the proportion of high school students who drop out in a defined period of time (1 year). The estimates show that the national yearly high school dropout rate was about the same in 1985 as it was in 1968. Improvement has occurred, however, since 1968 for specific racial groups as well as for some grade levels. PMID- 2332092 TI - Estimation of exposure time distributions. AB - In many demographic analyses, such as the assessment of environmental cancer risks, one may be interested not only in the age-by-state distribution of the population but also in the distribution of the population by time spent in a given state. States can represent geographic areas, marital statuses, labor force participation, or states of epidemiologic exposure. Recursive formulas for the calculation of the distribution of the population according to exposure time are derived under time-invariant state transition rates. Although populations can have identical growth rates and identical age-by-state distributions, they can have very different distributions by exposure time. An application to the analysis of carcinogenic exposure states is given, using data from Finland. The effect of population heterogeneity on the estimated exposure time distributions is studied. PMID- 2332094 TI - Blood pressure and microvascular complications in type 1 (insulin dependent) diabetic patients without hypertension. AB - To specify the influence of blood pressure on diabetic microangiopathy, the factors related to retinopathy and nephropathy were studied among 56 consecutive type 1 (insulin-dependent) diabetic out-patients without hypertension. Diabetes mellitus had been diagnosed for at least one year (mean duration of diabetes +/- SEM = 11.4 +/- 0.9 years). Diabetic patients did not take any treatment liable to influence blood pressure. Clinical parameters, including blood pressure, tobacco and alcohol consumption, were recorded by the same investigator. Retinopathy was defined as more than 5 microaneurysms on a fluorescein angiogram, clinical and incipient nephropathy as an albumin excretion rate over than 300 mg/d and between 30 and 300 mg/d, respectively. On average, retinopathy (n = 25) was associated with longer duration of diabetes (16.5 +/- 1.2 vs 7.4 +/- 0.9 years; p less than 0.001) and higher systolic blood pressure (136.2 +/- 4.1 vs 126.3 +/- 2.8 mm Hg; p less than 0.05). Clinical (n = 9) and incipient (n = 23) nephropathies were associated with duration of diabetes (17.9 +/- 2.0 and 11.8 +/- 1.7 vs 8.7 +/- 1.6 years, respectively; p less than 0.01), and with systolic (145.0 +/- 7.9, 132.7 +/- 4.7 vs 123.5 +/- 4.2 mm Hg; p less than 0.01) and diastolic blood pressure (83.3 +/- 6.2, 77.3 +/- 3.2 vs 72.2 +/- 3.4 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332093 TI - A study on the types of diabetes mellitus in first degree relatives of diabetic patients. AB - The genetic characteristics of the diabetic types have been assessed by following up their frequency in first degree relatives of some non-selected diabetic patients, registered at eight different centers of the country. Out of 1,003 non diabetic controls only 46 (4.6%) had 52 diabetic relatives, 65.4% of type 2 (non insulin-dependent). Comparatively, out of the 704 patients, 172 (24.4%) had 229 diabetic first degree relatives, 72.5 of type 2. Out of 231 type 1 (insulin dependent) diabetic patients, 29 (12.6%) had 34 diabetic relatives, 55.9% of type 1. Out of 300 type 2 patients, 99 (33.0%) had 121 diabetic relatives, 84.0% of type 2. The other 173 diabetic patients presented an "intermediary" type of the disease (needing insulin many years after onset). Forty-four (25.4%) of them had 64 diabetic relatives, 67.2% of type 2, 20.3% of type 1 and 12.5% with "intermediary" diabetes. The five times higher frequency of diabetes in patients' relatives versus controls is pointed out. Type 2 diabetic relatives predominated. The proportion of probands with diabetic relatives increased from 4.6% in non diabetics to 12.6% in type 1, to 25.4% in "intermediary" diabetes and to 33.0% in type 2. The heredity of type 1 prevailed in type 1 and that of type 2 in type 2 and in "intermediary" diabetes. The fact that "intermediary" diabetes tends towards type 1 (insulin-dependent) as therapy and towards type 2 (non-insulin dependent) as heredity might be an argument supporting the controversy on the diabetic syndrome classification. PMID- 2332095 TI - [Comparative effects of couscous and pasta on glycemia in normal subjects and type I diabetics]. AB - 8 healthy subjects have eaten in the morning, after an overnight fast, in two separated occasions and in a randomised order 50 gr of CHO as pasta or couscous. Blood glucose after pasta ingestion was lower at 30 mn (p less than 0.05) at 45 mn (p less than 0.01) and at 60 mn (p less than 0.05). Area under the curve after pasta was significantly reduced (p less than 0.01). In a second time 6 IDDM patients have eaten in a randomised order a meal made of pasta with tomato sauce (P = 11%, F = 30%, G = 59%) or couscous with vegetables and sauce (P = 10%, F = 37%, G = 53%). Blood glucose after the pasta was lower than couscous at 90 mn (p less than 0.05) the area under the curve after the pasta ingestion was reduced of 38% but did'nt reach significance. In conclusion couscous has a higher glycemic effect than pasta although it has a similar composition. This phenomenon is still observed when the cereal products are mixed with other foods and ingested by IDDM patients. PMID- 2332096 TI - Pulsatile rather than continuous glucagon infusion leads to greater metabolic derangements in insulin-dependent diabetic subjects. AB - The present study aimed at investigating the respective effects of continuous and pulsatile intravenous delivery of glucagon in insulin-dependent diabetic subjects. The study was performed in seven insulin-dependent diabetic subjects proven to have no residual insulin secretion. In random order and in different days each subject was submitted to glucagon delivery given continuously (58 ng/min) and in a pulsatile (377 ng/min during 2 min followed by 11 min during which no glucagon was infused) manner. In this conditions plasma glucose levels were significantly higher during pulsatile glucagon delivery. In particular in the last 65 min plasma glucose levels reached 10.8 +/- 0.3 vs 12.9 +/- 0.4 mmol/l (p less than 0.05) during continuous and pulsatile glucagon delivery respectively. Similarly plasma lipid changes also evidenced a greater effects of pulsatile rather than continuous hormone administration in producing the metabolic derangements classically encountered in insulin-dependent diabetic subjects. In conclusion, pulsatile glucagon delivery seem to produce greater metabolic effects than continuous hormone delivery. PMID- 2332097 TI - Effect of mitogens on the maximum activities of hexokinase, lactate dehydrogenase, citrate synthase and glutaminase in rat mesenteric lymph node lymphocytes and splenocytes during the early period of culture. AB - 1. The activities of hexokinase, lactate dehydrogenase and citrate synthase were maintained in mesenteric lymph node lymphocytes during 4 hr of culture: the activity of glutaminase increased during this period of time. 2. In splenocytes, the activity of hexokinase decreased markedly during the 4 hr period, whereas those of lactate dehydrogenase and glutaminase remained constant, and that of citrate synthase increased dramatically. 3. In both mesenteric lymphocytes and splenocytes, addition of the T-cell mitogens, phytohaemagglutinin or concanavalin A, to the culture medium caused decreases in the activities of both hexokinase and citrate synthase. 4. In contrast, these mitogens increased the activity of glutaminase in both cell types. 5. Addition of the B-cell mitogen, bacterial lipopolysaccharide, had little effect on hexokinase, lactate dehydrogenase or citrate synthase but increased markedly that of glutaminase in mesenteric lymph node lymphocytes. 6. In splenocytes this mitogen prevented much of the decrease in hexokinase activity, increased the activities of citrate synthase and glutaminase but had little effect on that of lactate dehydrogenase. PMID- 2332098 TI - ATP inhibition competes with activating cations in modulating the NAD(P)(+)-malic enzyme activity in the mitochondrial matrix of Xenopus laevis oocytes. AB - 1. ATP inhibits NAD(P)(+)-dependent malic enzyme activity by competing with the essential activators Mn2+ and Mg2+. 2. The kinetics fit an equation of co operative kind with Ki of 26 microM and KA of 11.3 microM for ATP/Mn2+ competition; with Ki of 1.1 mM and KA of 0.96 mM for ATP/Mg2+ competition. 3. In the absence of the inhibitor, the co-operativity index increases from 1.77 to greater than 4 in the presence of ATP, in the case of ATP/Mn2+ competition, while it increases from 1.88 to greater than 9 for ATP/Mg2+ competition. PMID- 2332099 TI - Developmental changes in the antigenicity and sugar-chain heterogeneity of rabbit alkaline phosphatases. AB - 1. Rabbit alkaline phosphatases (APs) clearly fused with the anti-human AP antibodies. In particular, fetal liver and kidney APs reacted slightly less with the anti-intestinal AP antibody as did adult enzymes, suggesting that intestinal AP-like isozyme is expressed at earlier stages of gestation in rabbit liver and kidney. 2. Immunohistochemical data indicated that intestinal AP-like isozyme in the kidney was mainly localized in the distal convoluted tubules and slightly in the proximal straight tubules, whereas liver/bone/kidney AP-like enzyme was found more in the glomeruli and interstitial capillary walls as a major component. 3. The sugar-chain heterogeneity of adult and fetal rabbit APs displayed organ specificity as did of rat and human APs. Moreover, in fetal development, the expression of high-mannose type or hybrid type sugar chains precedes the expression of complex type sugar chains in fetal development. PMID- 2332100 TI - Studies on the measurement of whole-body protein degradation in vivo in the chicken. AB - 1. An attempt was made to develop a new in vivo method for measuring whole-body protein degradation rate in chickens within an hour. For this purpose, two amino acid fluxes, absorption and protein synthesis were inhibited almost completely, followed by the measurement of changes in radioactivity and pool size in free amino acid pool. 2. The results indicated that the degradation rate estimated by the present direct isotope dilution method was not significantly different from that obtained by an indirect calculation based on the difference between the synthesis and net accretion rates in chicks fed ad libitum an adequate diet. 3. A computer-aided simulation analysis demonstrated that under the present circumstances incomplete inhibition of amino acid fluxes, i.e. absorption and protein degradation, affected the estimate of fractional rate of whole-body protein degradation, ranging from 75 to 110% of the experimentally-determined value. PMID- 2332101 TI - Studies on cholesterol accumulation in radicular cyst fluid--origin of heat stable cholesterol-binding protein. AB - 1. The amount of apolipoprotein B (apo B) was measured using slit-immunoblotting in 20 specimens of radicular cyst fluids. Apo B was detected in all the cyst fluids with varying amounts. 2. Relationship between the amounts of apo B and free cholesterol or activity of heat-stable cholesterol-binding protein (HCBP) were examined. The amount of apo B was correlated well with the activity of HCBP (n = 20, r = 0.72, P less than 0.01) and with the amount of free cholesterol (n = 20, r = 0.45, P less than 0.05). 3. Anti-human apo B antibody inhibited cholesterol-binding activity in radicular cyst fluid. 4. When human-serum was chromatographed on a HPLC ion-exchange column, both cholesterol-binding activity and apo B had exactly the same retention time. 5. These results suggest that HCBP originates from beta-lipoprotein, and beta-lipoprotein may have an important role in cholesterol accumulation on radicular cysts. PMID- 2332102 TI - Polytuftsin: a potential precursor for slow release of the phagocytosis stimulating peptide tuftsin. AB - 1. Polytuftsin (Thr-Lys-Pro-Arg)n, was synthesized through polycondensation of an amino-free and carboxyl-activated derivative of tuftsin, H2N-Thr-Lys(Z)-Pro Arg(Tos)-OSu, following suitable deprotection and fractionation steps. 2. Digestion of polytuftsin by trypsin, as well as by normal human serum, at 37 degrees C, yielded free tuftsin. 3. Polytuftsin affected the decreased formation of lung-metastasis, in B16 melanoma treated mice and prolonged the survival of animals more efficiently than tuftsin. 4. Tuftsin was found to be totally degraded by serum enzymes within approximately 60 min at 37 degrees C. PMID- 2332103 TI - Identification of essential amino acids in the active center of thyroidal NAD+ glycohydrolase. AB - 1. Purified thyroidal NAD+ glycohydrolase has been subjected to the action of a number of group specific reagents in order to gain information concerning its mode of action. 2. Modification of histidyl residues with diethylpyrocarbonate strongly suppresses the NAD+ glycohydrolase activity. Inactivation with this reagent can be reversed to some extent by subsequent treatment with hydroxylamine. 3. NAD+ and ADP-ribose partially protect against inactivation with similar efficiencies. 4. The incomplete reactivation with hydroxylamine after diethylpyrocarbonate treatment and the selective inactivation by 2,4-pentanedione indicates that apart from one or more essential histidyl residue(s) also lysyl residues are important for activity. NAD+ and to a smaller extent ADP-ribose again protect against inactivation by 2,4-pentanedione. 5. The sensitivity of the enzyme towards N-ethyl-5-phenyl-isooxazolium-3'-sulfonate further points to the importance of carboxylate containing side chains. 6. The mechanistic implications of these results are discussed. PMID- 2332104 TI - Pig lung 5'-nucleotidase: effect of diadenosine 5',5'''-P1, P4-tetraphosphate and its related compounds. AB - 1. A 5'-nucleotidase was purified from pig lung to apparent homogeneity. 2. Its kinetic properties were similar to those of the previously reported cytoplasmic 5'-nucleotidase, which preferentially hydrolyses IMP and GMP. 3. It was a tetramer composed of 69 kDa subunit. 4. It was effectively stimulated by diadenosine tetraphosphate and glycerate 2,3-bisphosphate. PMID- 2332105 TI - The effect of ketone bodies on protein turnover in isolated skeletal muscle from the fed and fasted chick. AB - 1. The addition of 4 mM acetoacetate or DL-beta-hydroxybutyrate to the incubation medium decreased the rate of protein synthesis without influencing the rate of protein degradation in extensor digitorum communis (EDC) muscles from fed chicks and decreased the rates of protein synthesis and degradation in muscles from fasted chicks. 2. Ketone bodies markedly decreased intracellular concentrations of glutamine in EDC muscles from fed chicks by increasing glutamine oxidation. 3. The addition of 0.5 mM glutamine to incubation media containing 1.0 mM glutamine reversed the ketone body-induced decrease in intracellular glutamine concentration to the control value and blocked the inhibiting effect of ketone bodies on protein synthesis in skeletal muscles from fed chicks. 4. The addition of 5 mM pyruvate blocked the ability of ketone bodies to increase glutamine oxidation and prevented the associated decrease in intracellular glutamine concentration and the rate of protein synthesis in EDC muscles from fed chicks. 5. These results suggest that ketone bodies can act directly on skeletal muscle to inhibit the rate of protein synthesis in muscles from fed chicks by decreasing intracellular glutamine concentration by increasing its oxidation. PMID- 2332106 TI - Inhibition of nuclear T3 binding by fatty acids: dependence on chain length, unsaturated bonds, cis-trans configuration and esterification. AB - 1. Fatty acids have the capacity for inhibition of nuclear T3 binding (INB). The present studies were undertaken to describe the INB-activity of fatty acids as a function of chain length, unsaturated bonds, cis-trans configuration, and esterification. 2. Isolated rat liver nuclei were incubated with [125I]T3 in the absence or presence of fatty acids in concentrations of 0.011, 0.033, 0.1 and 0.3 mM respectively. 3. INB-activity depended on the chain length, being greatest at 14 carbon atoms. 4. INB by unsaturated fatty acids was greater than that of saturated fatty acids, and increased with increasing number of double bonds. 5. Fatty acids in the cis configuration had greater INB-activity than those in trans configuration. 6. Esterification of fatty acids decreased INB-activity: monoglycerides still had some effect, but di- and triglycerides had no effect. PMID- 2332107 TI - A comparison of the structure and properties of normal human transferrin and a genetic variant of human transferrin. AB - 1. A rare genetic variant of human serum transferrin (TfBSHAW) is reported. 2. The variant and normal transferrins have been purified. 3. The two proteins have been shown to be identical with respect to their molecular weights, heat stability, iron uptake and absorbance spectra. 4. The amino acid substitution is thought to be isoleucine replaced by asparagine at either position 378 or position 381. 5. The ferric iron bound to the C-site of TfBSHAW is unstable in the presence of protons or 6 M urea. PMID- 2332108 TI - Human urinary and renal alpha-L-fucosidases. A comparative study. AB - 1. Enzymatic forms of alpha-L-fucosidase from human renal tissue and urine were investigated. 2. In renal tissue two different isoenzymatic patterns were obtained by chromatofocusing of either directly soluble or detergent solubilized extracts. 3. On the other hand the urinary isoenzymatic pattern is similar to that obtained for the renal soluble extract. PMID- 2332109 TI - Comparative study of the N-glycoprotein synthesis through dolichol intermediates in mitochondria, Golgi apparatus-rich fraction and endoplasmic reticulum-rich fraction. AB - 1. Glycosylation of endogenous dolichol acceptors was higher in mitochondria than in C 30,000 g (Golgi apparatus-rich fraction) and C 100,000 g (endoplasmic reticulum-rich fraction). 2. In mitochondria, N-glycoprotein biosynthesized were composed of high mannose type and non-fucosylated biantennary complex type while in C 30,000 g and C 100,000 g preparations, they contained biantennary complex type as tri and tetraantennary complex type oligosaccharides in both fucosylated and non-fucosylated forms. PMID- 2332110 TI - Lactating mouse mammary cell uptake of 59Fe-transferrin. The effect of KCN, 2,4 dinitrophenol, ethanol and ATP. AB - 1. Amounts of KCN of 0.2, 1.0 and 2.0 X 10(-11) mol in a probe do not prevent the uptake of transferrin iron from lactating mouse mammary gland cells. 2. The effect of 5, 10 and 100 X 10(-11) mol in a probe 2,4-dinitrophenol dissolved in 20% ethanol is also negative on the iron-transferrin uptake from the cell. 3. There is a statistically significant decrease of uptake of transferrin-iron under the influence of 20% ethanol in the incubation mixture (25, 50 and 100 microliters). The effect of ethanol is diminished by 2,4-dinitrophenol in the solution. 4. The uptake of 59Fe-transferrin from cells of lactating gland was blocked by ATP (in amounts 0.5, 1.0 and 10.0 X 10(-11) mol per probe) while other concentrations have no effect. It seems that ATP does not release 59Fe from transferrin, nor help the iron uptake from the cells. 5. All evidence indicates that the uptake of transferrin-iron from lactating mammary gland cells is not an energy dependent process. PMID- 2332111 TI - Cytochrome P-450 in the brain. PMID- 2332112 TI - Is small beautiful? PMID- 2332113 TI - Biochemistry in the Oxford tutorial system: better teaching or wasted effort? PMID- 2332114 TI - Keller Plan teaching in first year biochemistry. PMID- 2332115 TI - Small-group teaching of biochemistry in the medical student laboratory. PMID- 2332116 TI - Metabolic effects in a murine cachexia model. PMID- 2332117 TI - Effect of puberty on initial kidney growth and rise in kidney IGF-I in diabetic rats. AB - Prepubertal subjects have a low incidence of diabetic nephropathy compared with duration-matched postpubertal subjects. At puberty, there is an increase in insulinlike growth factor I (IGF-I) levels, and because IGF-I has been implicated in the early kidney enlargement of experimental diabetes, we studied the development of kidney enlargement and kidney IGF-I levels in prepubertal (aged 5 wk) and postpubertal (aged 13 wk) Sprague-Dawley rats during the 7 days after induction of diabetes with streptozocin. Kidney weight in postpubertal diabetic animals was significantly greater than in postpubertal controls by day 2 (1.46 +/ 0.06 vs. 1.16 +/- 0.09 g, P less than 0.05), and by day 7, kidney weight had increased by 36% (1.61 +/- 0.07 vs. 1.18 +/- 0.08 g, P less than 0.001). Despite comparable blood glucose levels in the prepubertal and postpubertal diabetic rats, kidney weight in prepubertal diabetic animals was significantly greater than in prepubertal controls by 14% on day 7 only (0.84 +/- 0.01 vs. 0.73 +/- 0.03 g, P less than 0.05). Kidney IGF-I content was significantly elevated in diabetic postpubertal rats, peaking on day 1 (diabetic vs. control, 1082 +/- 156 vs. 543 +/- 21 ng/g, P less than 0.001) and day 2 but not in prepubertal diabetic rats. Thus, prepubertal diabetic rats have reduced and retarded kidney growth and attenuated kidney IGF-I levels, suggesting that local IGF-I accumulation may play an important role in diabetes-associated kidney enlargement. PMID- 2332118 TI - Uptake of myo-inositol by early-somite rat conceptus. Transport kinetics and effects of hyperglycemia. AB - We have shown that myo-inositol in the cultured rat embryo is diminished whenever malformations are induced by hyperglycemia and that the malformations and reductions of tissue myo-inositol content are not corrected by aldose reductase inhibitors. This study was designed to evaluate the kinetics of myo-[3H]inositol uptake in vitro during 1-, 3-, and 24-h intervals in the 10.5-day rat conceptus (10-12 somites). We found that the equilibration between tissue and medium is relatively slow and that the concentration of free myo-inositol in tissue is only approximately threefold greater than in the medium even after 24 h. The integrated uptake of free myo-inositol by the intact 10.5-day conceptus is a saturable process with a Km (246 +/- 16 microM) consistent with a low-affinity system. The net rate of accumulation into the tissue pool of free myo-inositol exceeds the rate of incorporation of the accumulated myo-inositol into lipid components. Ambient glucose inhibits net myo-inositol uptake in a concentration dependent fashion, and the inhibition is competitive in nature. The glucose mediated inhibitions of myo-inositol transport also compromise the concurrent incorporation of myo-[3H]inositol into lipid components, although to a lesser extent. These inhibitory effects are relatively specific for D-glucose and not replicated by equimolar additions of D-mannose or D-galactose. myo-Inositol accumulation by the 10.5-day rat conceptus is also impaired by relatively specific inhibitors of D-glucose transport such as phloridzin or ouabain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332119 TI - Effect of streptozocin-induced diabetes on insulin-receptor tyrosine kinase activity in obese Zucker rats. AB - We examined insulin binding, insulin-stimulated autophosphorylation, and phosphorylation of poly(Glu.Na,Tyr)4:1 by liver and skeletal muscle insulin receptor from lean, obese, and obese streptozocin-induced diabetic Zucker rats. Induction of diabetes with streptozocin (30 mg/kg) lowered the lasting insulin level from 11.4 to 3.8 ng/ml, which was not significantly greater than the lean control level. Autophosphorylation and tyrosine kinase activity of liver insulin receptors were increased 70-100% in the obese control group (relative to lean rats), but diabetes reversed this hyperresponsiveness to insulin. In muscle, obesity was associated with a 40-50% decrease in autophosphorylation and tyrosine kinase activity, which was also reversed in the diabetic state. Autophosphorylation and tyrosine kinase activity were significantly correlated in liver and muscle and were also correlated with fasting insulin levels. These data suggest that insulin-receptor tyrosine kinase activity is regulated differently in liver and muscle and that the abnormalities in kinase activity associated with the obese Zucker rat are at least partly secondary to hyperinsulinemia. PMID- 2332120 TI - Cholesterol metabolism in alloxan-induced diabetic rabbits. AB - The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2 monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated with lipid and lipoprotein levels. Although intestinal HMG-CoA reductase activity was significantly increased (P less than 0.001) in poorly controlled compared with moderately controlled diabetic rabbits, there was a significant reduction in the activities of intestinal ACAT (P less than 0.01), hepatic HMG-CoA reductase (P less than 0.05) and ACAT (P less than 0.001), and phenol 2-monooxygenase (P less than 0.01). The poorly controlled animals were hypercholesterolemic (P less than 0.01), and this was reflected in the very-low density and high-density lipoprotein fractions. Serum cholesterol levels in the nondiabetic and moderately controlled diabetic groups were similar. This increase in intestinal HMG-CoA reductase activity in the poorly controlled diabetic animals occurred in the absence of hyperphagia. Although abnormalities in cellular cholesterol metabolism could be partly responsible for the alterations in serum cholesterol levels in diabetes, the precise mechanisms underlying these enzymatic changes have yet to be elucidated. PMID- 2332121 TI - Hand dominance of parents and other relatives of autistic children. AB - Hand preferences of 219 mothers and 186 fathers of autistic children were assessed using the Annett Handedness questionnaire. Subgroups of 54 mothers and 57 fathers with a family history of language-related developmental disorders were identified. Parents also reported the handedness of other relatives. Mothers (but not fathers) in the main group were significantly more likely to be consistently right-handed than females in the general population, but this was not specifically associated with a family history of language problems. There was no evidence of an increased incidence of consistent left-handedness in either the whole group of parents or the subgroups. Reported handedness of other relatives showed no abnormal distribution in relation to a comparison group. The findings are discussed in relation to theories about genetic factors in language-related developmental disorders in general, and autism in particular. PMID- 2332122 TI - Lipid-containing cells in the brain in sudden infant death syndrome. AB - The authors report a semi-quantitative autopsy study on the content of lipid containing cells (LCC) in corpus callosum and periventricular frontal white matter from the brains of 96 infants. These were 55 cases of sudden infant death syndrome (SIDS), 28 with conditions expected to have caused hypoxia (hypoxic control), and 13 with conditions not expected to have caused more than brief, terminal hypoxia (non-hypoxic control). Appreciable numbers of LCC were found in the non-hypoxic control cases, but significantly more LCC were found in the hypoxic controls. LCC in SIDS cases were intermediate between the non-hypoxic and hypoxic controls. The findings are discussed in the light of an experimental primate study. The authors conclude that the slight excess of LCC in SIDS cases is more likely to be an exaggeration of normal developmental LCC accumulation than evidence of pre-terminal episodes of hypoxia. PMID- 2332123 TI - Increased risk of cerebral palsy among very low-birthweight infants with chronic lung disease. AB - To determine the risk of cerebral palsy and other forms of neurosensory impairment in very low-birthweight infants (less than 1500g) with severe lung disease, as compared with those with lesser degrees of lung disease, and to examine perinatal and demographic correlates of chronic lung disease, the authors prospectively followed 249 survivors born between 1983 and 1984. 52 (21 per cent) developed chronic lung disease (CLD), defined as oxygen dependence greater than or equal to 28 days. 15 per cent of children with CLD developed cerebral palsy, compared with 3 per cent who required oxygen for between three and 27 days and 4 per cent of those requiring oxygen for two days or less. The overall neurological impairment rate, including cerebral palsy, abnormalities of muscle tone, hydrocephalus requiring a shunt, and severe visual or hearing impairment, was 29 per cent for infants with CLD. This compares with rates of 9 per cent for those requiring oxygen for between three and 27 days and 6 per cent for those on oxygen for two or less days. Infants with CLD had a significantly lower mean birthweight and gestational age; 43 per cent had grade III or IV intraventricular hemorrhages; and they also required longer periods in hospital. PMID- 2332124 TI - Energy expenditure index of walking for normal children and for children with cerebral palsy. AB - Energy expenditure indices (EEI) based on oxygen uptake and heart rate were used to compare the economy of walking at various speeds by normal and cerebral palsied children. At low walking speeds, EEI values were high, indicating poor economy. At higher speeds the EEI values decreased until a range of maximum economy was reached. For normal children who were capable of walking beyond this range at higher speeds, the EEI increased again. This pattern was noted for both oxygen-uptake and heart-rate indices. Mean EEI values based on oxygen uptake and heart rate for normal children were significantly lower and occurred at faster walking speeds than values for children with cerebral palsy. EEI based on either oxygen uptake or heart rate can be used clinically to provide objective information to help evaluate the influence on gait function of surgical intervention, ambulatory aids or orthotics. PMID- 2332125 TI - An extended family with a dominantly inherited speech disorder. AB - A three-generation family is described in which 16 members have a severe developmental verbal dyspraxia. Inheritance is autosomal dominant, with full penetrance. Intelligence and hearing are normal. PMID- 2332126 TI - The normal crying curve: what do we really know? PMID- 2332127 TI - Are nurses united in caring? PMID- 2332128 TI - Women who made a difference. PMID- 2332129 TI - [Precursor cells of the granulomonocytopoiesis in children with immune neutropenia]. AB - The study of precursor cells of granulocytes and macrophages has shown that in children with immune neutropenia the higher division of granulopoiesis-committed precursor cells is not affected, while the defect is localized in the periphery of hemopoiesis, and it is induced by increased destruction of neutrophils. PMID- 2332130 TI - ["Centrocytic leukemia"--a new variant of chronic lymphocytic leukemia?]. AB - A patient has been described with an unusual variant of B-cell lymphoid leukemia. Specific morphology of leukemic cells (the presence of nuclear cleavage), initial and principal localization of the process in the bone marrow, as well as an original phenotype of malignant cells (CD5+, CD35+, CD37+ and CD38+) have given the grounds for the designation of this rare variant of leukemia as centrocytic. PMID- 2332131 TI - [Antigen, common for mature human B- and T-lymphocytes, detected with the use of autolymphocytotoxins]. AB - The investigation of adsorption capacity of B- and T-lymphocytes in respect to autolymphocytotoxic antibodies (ALCTA) has shown that these two populations of mature cells have a common antigen against which ALCTA are directed. This antigen is insufficiently expressed of pathologic cells of patients with B-cellular variant of chronic lymphoid leukemia (CLL). B-lymphocytes of patients with malignant non-Hodgkin's lymphoma, hairy-cell leukemia, Waldenstrom's macroglobulinemia are more mature, as compared to those of CLL patients, and carry surface antigens to which autoantibodies are directed. PMID- 2332132 TI - [Early hematopoietic stem cells (pre-CFU) studied in long-term culture of murine bone marrow]. AB - A new category of primitive hemopoietic stem cells determined in murine bone marrow long-term culture (CFU-BMLTC) is described. The novel precursors give rise to hemopoietic colonies corresponding to "cobble stone" areas observed on the adherent cellular layer. The linear relationship between the colony number and the dose of bone marrow cells explanted in the culture has been discovered. Radiosensitivity of the new type of hemopoietic precursors in the bone marrow of adult mice is characterized by D0-1.28 Gy. CFU-BMLTC were also identified in 13 day mouse fetal liver. In contrast to CFUs the precursors described are less sensitive to extensive in vivo treatment with hydroxyurea. The data obtained have permitted the authors to make a conclusion on a higher status of CFU-BMLTC as compared to CFUs in the hemopoietic stem cell hierarchy. PMID- 2332133 TI - [Normal hematopoiesis]. PMID- 2332134 TI - [Occurrence of anti-delta agent antibodies in the USSR and Czechoslovakia]. PMID- 2332135 TI - [Optimal industrial conditions for the production of antistaphylococcal immunoglobulin]. PMID- 2332136 TI - [A magnetophoretic method of diagnosis of glucosephosphate dehydrogenase deficiency in the erythrocytes]. PMID- 2332137 TI - [Induced hematopoietic foci in mice. I. Induction of extraskeletal hematopoietic areas using demineralized tooth matrix]. AB - Conditions of formation of induced osteo-hemopoietic foci in mice, in response to ectopic implantation to them of homologous demineralized tooth matrix, have been studied. It is shown that the hemopoietic tissue of the induced foci is similar to the bone marrow of the skeletal bones by the morphological parameters and cellular composition; differentiation of precursor cells takes place in all three directions of myelopoiesis. Induced foci formation under the capsule of the kidney occurs much later (after 5-8 months) than under the skin of muscular fascia (1-1.5 months). The induced hemopoietic foci functioning continues at least for one year. PMID- 2332138 TI - Effects of probenecid on striatal dopamine depletion in acute and long-term 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. AB - 1. The effect of probenecid on striatal dopamine depletion in acute 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice was examined. 2. Mice treated with a single dose of MPTP (15 mg/kg, s.c.) showed a significant depletion of striatal dopamine throughout a time-course of 7 days. Interestingly, this MPTP-induced striatal dopamine depletion was potentiated by a concomitant injection with a single dose of probenecid (250 mg/kg, i.p.). 3. However, this potentiation of dopamine depletion by probenecid was only a transient phenomenon seen at 4-5 days after the treatment. 4. In a long-term study, mice were treated with the same dosages of MPTP or probenecid plus MPTP twice a week for 5 weeks, we detected that probenecid plus MPTP caused a persistent depletion of striatal DA for 6 months. 5. During this period a partial recovery of DA levels was seen with MPTP alone-treated mice. 6. The detailed mechanisms by which probenecid causes acute potentiation and persistent long-term depletion of striatal dopamine by MPTP are still unclear. 7. With the evidence presented in this study, we determined that after the administration of MPTP in mice, the drug was rapidly metabolized in the periphery and excreted as MPTP N-oxide. 8. Probenecid was shown to inhibit the excretion of urine and urinary MPTP N-oxide shortly after MPTP administration, which may directly or indirectly increase the neurotoxic action of MPTP in mice. PMID- 2332139 TI - [3H]5-hydroxytryptamine uptake and release in cat cerebral arteries. AB - 1. Field electrical stimulation induced tritium release from cat cerebral arteries preincubated with [3H]serotonin (5-HT). 2. This release was markedly reduced by tetrodotoxin (0.8 microM), B-HT 920 (1 microM), denervation with 6-OH dopamine (6-OHDA) and OCa2+, and increased by phentolamine (1 microM) and phorbol 12,13-dibutyrate (1 and 3 microM). 3. 5-HT (10 and 100 microM) and NA (0.1, 1 and 10 microM) caused concentration-dependent tritium release in control arteries, but not in those denervated with 6-OHDA. 4. [3H]5-HT uptake was greatly reduced by preincubation of arteries with cocaine (10 microM), ouabain (100 microM) or denervation with 6-OHDA. 5. 5-HT did not amplify contractions elicited by noradrenaline (NA) in middle cerebral arteries. 6. These data indicate: (1) 5-HT is mainly accumulated in adrenergic nerve endings; (2) 5-HT release is modulated by presynaptic alpha 2-adrenoceptors; (3) protein kinase C of perivascular adrenergic nerve endings participates in 5-HT release, and (4) 5-HT did not amplify NA responses. PMID- 2332140 TI - Potentiation of cholinergic activity with pyridino[1,2-a]imidazo[5,4-b]indole: in vitro studies. AB - 1. Effects of a novel imidazoindole derivative on cholinergic function were studied in isolated tissue preparations. 2. The compound demonstrated a dose dependent (10(-11)-10(-9) potentiation (20-60%) of acetylcholine induced tension in guinea pig ileal tissue. 3. Increases in the size of end-plate potentials and nerve evoked muscle twitches were observed in frog nerve-skeletal muscle preparations. 4. Cholinesterase activity was not inhibited. 5. The results suggest that the compound has actions at the post-synaptic muscarinic receptor complex in smooth muscle and causes pre-synaptic increases in ACh release at the neuromuscular junction. PMID- 2332141 TI - The effect of cyanide intoxication on hepatic rhodanese kinetics. AB - 1. Results of studies on the kinetics of hepatic rhodanese and the effects of S adenosyl-L-methionine (SAM) on these kinetic parameters in cyanide-treated and non-treated mice are reported here. 2. The enzyme exhibited typical Michaelis Menten behaviour with cyanide inhibition at concentrations higher than 50 mM. Km values of 4.74 and 0.85 mM were obtained for thiosulphate and cyanide, respectively, in control mice. 3. These results stress the biological importance of the rhodanese reaction for cyanide detoxification. 4. Km values were not significantly modified when the animals were intoxicated with a lethal (20 mg/kg) or a non-lethal (4 mg/kg) dose of cyanide. 5. SAM treatment either in control or in cyanide-poisoned animals doubled the Km's for cyanide. PMID- 2332142 TI - Changes in 5-HT1 receptors in different brain structures of rats with isolation syndrome. AB - 1. Prolonged (3 month) individual housing of Wistar rats produced aggressive muricidal behavior in 28% of the animals. 2. Binding studies with [3H]5-HT showed that the affinity (Kd) of 5-HT1 receptors in the frontal cortex, striatum, hippocampus and hypothalamus of isolated aggressive rats was significantly decreased as compared to that in grouped rats. 3. The affinity of 5-HT1 receptors was also significantly decreased in the striatum, hippocampus and hypothalamus of isolated nonaggressive rats. 4. The number (Bmax) of 5-HT1 receptors was significantly decreased in the hippocampus and hypothalamus of isolated aggressive rats and in isolated nonaggressive rats it was decreased only in the hypothalamus. 5. The data suggest that aggressive muricidal behavior in rats with syndrome of social isolation is connected with the decreased activity of brain 5 HT1 receptors. PMID- 2332143 TI - The effects of dietary marine fish oils (omega-3 fatty acids) on coagulation profiles in men. AB - 1. This study was undertaken to evaluate the effects of low dose ingestion of omega-3 fatty acids on clotting profiles in healthy men ingesting 3 g of MaxEPA (900 mg omega-3 fatty acids) daily for 30 days. 2. No effect was noted on either platelet aggregation or circulating prostaglandin levels. 3. Significant decreases were noted for total cholesterol and low density lipoprotein. 4. Clotting factor decreases were noted for factors primarily of the intrinsic pathway and several factors which promote fibrinolysis. 5. The data suggests that low level ingestion of marine fish oil has a beneficial effect on lipids and possibly the clotting profiles in healthy men. PMID- 2332144 TI - Calcium uptake activity of cardiac sarcoplasmic reticulum in myo-inositol-treated diabetic rats. AB - 1. Cardiac function of STZ-diabetic rats has been shown to be partially improved by myo-inositol treatment. We studied the effect of myo-inositol on Ca2(+)-uptake activity in sarcoplasmic reticulum in diabetic animals. 2. Cardiac sarcoplasmic reticulum Ca2(+)-uptake activity was significantly depressed in 8-week diabetic rats. 3. Myo-inositol treatment could not improve Ca2(+)-uptake activity in diabetic rats. 4. The data suggest that the cardiac dysfunction in diabetic rats is due to factors other than the decreased Ca2(+)-uptake activity in sarcoplasmic reticulum. PMID- 2332145 TI - Stereoselectivity of NC-1100, a Ca-entry blocker. AB - 1. Stereoselectivity of NC-1100 in Ca-entry blocking activity was tested in the guinea pig taenia caecum. 2. Racemic, (-)- and (+)-NC-1100 shifted the contraction-response curve of CaCl2 towards higher concentration in a parallel manner suggesting a competition. 3. (-)-NC-1100 was about 3 times as potent as (+)-NC-1100. 4. Potency of racemic NC-1100 was intermediate between those of (-)- and (+)-NC-1100. PMID- 2332146 TI - Ovaries and regulation of juvenile hormone titer in Acheta domesticus L. (Orthoptera). AB - A study was performed on females Acheta domesticus to examine the effects of various experimental conditions on the ovarian physiology. Using a radioimmunoassay to determine juvenile hormone (JH) titers as well as in vitro JH biosynthesis, we observed that retention of mature follicles in egg-retaining females, i.e., virgins or mated females not provided an egg-laying substrate, inhibits JH production and consequently oocyte development. Mating in intact as well as ovariectomized females does not affect corpora allata activity. It is only when mating is associated with egg laying that JH biosynthesis and hemolymph titers increased and oocyte development and fecundity are stimulated. Despite lower JH biosynthesis, ovariectomized females present enlarged corpora allata and the levels of JH observed in their hemolymph were intermediate between those of intact egg-laying and virgin females. In intact females, the hemolymph JH titers as well as the JH esterase activities were related to ovarian development. JH esterase activity was very high in ovariectomized animals. Several factors involved in ovarian development of A. domesticus are discussed. PMID- 2332147 TI - Neurohypophysial hormones and cardiac activity in the frog, Rana tigrina, and in the snake, Ptyas mucosa. AB - The cardiac effects of neurohypophysial hormones (NH) in the frog, Rana tigrina, and in the snake, Ptyas mucosa, were studied in isolated atrial preparations. Arginine vasopressin (AVP), vasotocin (AVT), isotocin (ISN), mesotocin (MSN), and oxytocin (OXY) produced dose-related positive chronotropic and inotropic responses in the frog atria. AVT was the most potent. In the snake, AVP, AVT, MSN, and OXY produced dose-related positive inotropic but not chronotropic changes. OXY was the most potent. Data indicate that there is a direct action of NH on the heart in both animals, the atrial rate and tension responses to NH are not coupled, and judging by the efficacy, AVT and OXY might be the natural NH in the frog and snake, respectively, which may account for the high concentrations required of other NH to be cardiac stimulating. PMID- 2332148 TI - Purification, characterization, and molecular cloning of gonadotropin subunits of silver carp (Hypophthalmichthys molitrix). AB - The alpha and beta subunit of silver carp gonadotropin (scGTH-alpha and scGTH beta) were isolated by high-performance liquid chromatography. Heterogeneity of N terminal amino acid sequence was observed in scGTH-alpha but not in scGTH-beta. For determining the complete primary structures of scGTH-alpha and scGTH-beta, their cDNAs were cloned. Combining the data of N- and C-terminal sequences determined from proteins and the amino acid sequences deduced from cDNAs, we infer that scGTH-alpha consists of 95 and/or 93 residues and scGTH-beta consists of 115 residues. Both scGTH-alpha and scGTH-beta are glycoprotein. Their carbohydrate content is about 20 g per 100 g protein. The molecular weights of scGTH-alpha and scGTH-beta were calculated to be 12,700 and 15,700 Da, respectively. The amino acid sequences of scGTH-alpha and scGTH-beta are very similar to those of the corresponding subunit of carp GTH, different in only 2 and 4 residues, respectively. In addition, a high extent of homology (70%) was also observed between the alpha subunits of fish and mammalian GTHs. In the case of beta subunit, homology among various species of fish (75 to 98%) is much higher than that between fish and mammal (40%). These data suggest that the alpha subunit is conserved while the beta subunit is diversified during the molecular evolution of vertebrate GTH. PMID- 2332149 TI - The acute effects of food and glucose challenge on plasma thyroxine and triiodothyronine levels in previously starved rainbow trout (Oncorhynchus mykiss). AB - The acute effects of a single meal on plasma L-thyroxine (T4) and 3,5,3'-triiodo L-thyronine (T3) levels were examined in rainbow trout starved for 3 days. Plasma T4 increased within 2 hr of food intake and remained elevated to 8 hr. Plasma T3 was not altered consistently. Feeding-induced elevations in plasma T4 were present only in trout weighing less than 250 g and if they consumed a ration exceeding 0.38% of body weight. Postprandial elevations in plasma glucose paralleled those in plasma T4, suggesting a possible relationship between glucose intake and food-induced alterations in plasma T4. In trout intraperitoneally (ip) injected 4 hr earlier with 0.7% NaCl containing 0.2 or 2.0 g/kg D-glucose, plasma T4 increased relative to that in saline-injected controls. In starved trout cannulated in the dorsal aorta to permit serial blood removal, ip injection of glucose (0.85 g/kg) increased plasma glucose at 1 hr and plasma T4 at 2 hr, but did not alter plasma T3. It is concluded that enhanced glucose availability associated with feeding starved trout contributes to the postprandial elevation in plasma T4. PMID- 2332150 TI - The complete amino acid sequences of alpha subunits of chum salmon gonadotropins. AB - The complete amino acid sequences of alpha subunits of chum salmon (Oncorhynchus keta) gonadotropins (GTHs), GTH I and GTH II, were determined. Subunits were separated by reversed-phase high-performance liquid chromatography. Two alpha subunits, I alpha 1 and I alpha 2, were obtained from GTH I, whereas only one alpha subunit was obtained from GTH II. Sequence analysis revealed that GTH I alpha 2 is identical to GTH II alpha, but distinct from GTH I alpha 1. The I alpha 1 and II alpha consist of 95 and 92 amino acid residues, respectively. GTH I alpha 1 has 72% sequence identity with GTH I alpha 2. The two alpha subunits show approximately 65% sequence identity with bovine alpha subunit. This is the first finding of two chemically distinct alpha subunits from one species. PMID- 2332151 TI - Sex steroid levels in developing and adult male and female zebra finches (Poephila guttata). AB - Serum samples from male and female zebra finches ranging in age from 1 day before hatch to 54 days posthatch were assayed for 17 beta-estradiol (E), androgen, testosterone (T), or 5 alpha-dihydrotestosterone (DHT). Additional samples were assayed from intact and gonadectomized adults, gonadectomized adults with intraperitoneal implants of testosterone propionate (TP) or estradiol benzoate (EB), gonadectomized nestlings, and nestlings injected subcutaneously with EB. DHT levels of developing birds did not vary as a function of either sex or age. During development, average androgen and T levels were highest during the nestling period, prior to sexual maturation, and were higher in females than in males. Endogenous androgen levels of most subjects that were sampled repeatedly rose and then declined between 24 and 49 days. TP implants produced higher T levels in adult females than in adult males. Levels of E were higher in both sexes during the hatching period (Days -1 through 0) than during the nestling period (Days 2 through 14). A greater number of males than females had relatively high E levels on Days 12 and 14 and during the second week overall. There was no sex difference in levels of E in adults, and gonadectomized adults had markedly higher E levels than intact adults. Gonadectomized nestlings had the same androgen and E levels as intact nestlings of the same age; EB injected nestlings had elevated E levels. The present results indicate specific endocrine changes that mirror events crucial to sexual differentiation of endocrine and behavioral components of reproduction, and have important implications for models of sexual differentiation in zebra finches. PMID- 2332152 TI - Evidence against dormancy in the bacterial fish pathogen Aeromonas salmonicida subsp. salmonicida. AB - Results indicate that A. salmonicida does not enter an unculturable dormant state. The resuscitation of dormant cells by nutrient broth described by previous workers appears to be due to the presence of small numbers of viable, culturable cells too few to be detected by the sampling protocol employed. PMID- 2332153 TI - Effects of DNase production, plasmid size, and restriction barriers on transformation of Vibrio cholerae by electroporation and osmotic shock. AB - Attempts to transform wild type strains of V. cholerae with plasmid DNA by traditional osmotic shock methods were not successful. A mutant of V. cholerae that was deficient in extracellular DNase was transformed with plasmid DNA by osmotic shock, demonstrating directly that extracellular DNase is a major barrier to transformation of V. cholerae. Transformation of wild type and DNase-negative strains of V. cholerae was accomplished by electroporation. Efficiency of transformation by electroporation increased with field strength, decreased with plasmid size, and was relatively insensitive to changes in the electrolyte composition of the buffer as long as isotonic sucrose was present. Host controlled modification/restriction systems also affected transformation efficiency in V. cholerae. PMID- 2332154 TI - Analysis of the 2-keto-3-deoxyoctonate (KDO) region of lipopolysaccharides isolated from non-01 Vibrio cholerae 05R. AB - Phosphorylated 2-keto-3-deoxyoctonate (KDO) has been detected in the strong-acid hydrolysates of lipopolysaccharides (LPS) of family Vibrionaceae including Vibrio cholerae. Structural analysis of LPS isolated from a rough mutant of non-01 V. cholerae 05 by dephosphorylation, periodate oxidation and methylation analysis revealed that the inner core region of the LPS molecule contains only one mole of KDO in contrast to enteric Gram-negative bacterial LPS, and that the phosphate group on the KDO molecule resides in the C4 position, while the site of binding of KDO to heptose, a constituent of the distal part of the inner core region, is the C5 position as in the enteric bacterial LPS. PMID- 2332155 TI - Production of monoclonal antibody against a hemolysin (Vp-TRH) produced by Vibrio parahaemolyticus. AB - The antigenicity of a hemolysin (Vp-TRH: Vp-TDH related hemolysin) produced by Kanagawa phenomenon-negative clinical isolates of Vibrio parahaemolyticus was studied using monoclonal antibodies (MAbs). A total of 12 hybridoma clones which produced MAbs against Vp-TRH were established. All MAbs contained the Kappa light chain and were IgG type. These MAbs were divided into a minimum of 5 different specificity groups, including antibodies specific to Vp-TRH and common to both Vp TRH and Vp-TDH, a possible pathogenic toxin of Kanagawa phenomenon-positive V. parahaemolyticus. These results clearly show the immunological similarity and dissimilarity (specificity) of Vp-TRH and Vp-TDH. PMID- 2332156 TI - Involvement of plasmids in Streptomyces incarnatus phenotype. AB - The sinefungin producing, pock forming strain Streptomyces incarnatus was shown to be thiostrepton resistant. However, it does not produce thiostrepton and structurally related antibiotics. In this strain, five low copy plasmids of variable sizes were detected with electron microscopy. The strain S. lividans TK24 became thiostrepton resistant upon transformation by one of the plasmids of S. incarnatus. PMID- 2332157 TI - Complete nucleotide sequence of the sr gene from Streptococcus mutans OMZ 175. AB - The nucleotide sequence encoding the SR protein of Streptococcus mutans OMZ 175 (serotype f) has been determined. The sr gene consists of 4667 bp and codes for a 171177 Da protein. Comparison of the inferred amino acid sequence with the one of PAc antigen from S. mutans MT 8148 (serotype c) indicates a 88% conservation of amino acid residues which reflects the close relatedness of both proteins. Major differences in amino acid composition are located at the C-terminal part of the sequence where only 298 amino acids of the terminal 420 are conserved. PMID- 2332158 TI - Effect of iron limitation on protein composition and ultrastructure of Haemophilus ducreyi. AB - Protein profiles of whole cells of Haemophilus ducreyi grown in the presence or absence of the iron chelator desferal, were compared by polyacrylamide gel electrophoresis. Each of four strains produced novel proteins in the range 43-160 kDa when cultured under conditions of reduced iron availability. At some sub inhibitory concentrations, desferal produced enhanced growth, possibly due to it functioning as an exogenous siderophore. Organisms grown under conditions of reduced iron availability ultrastructurally showed also large periplasmic spaces between cytoplasm and outer membrane. PMID- 2332159 TI - Directed mutagenesis of selected regions of a Bacillus thuringiensis entomocidal protein. AB - Comparison of the sequences of Bacillus thuringiensis entomocidal toxins of widely differing specificity reveals six conserved domains. The role of one of the most highly conserved domains (D1) located near the N-terminus has been investigated by site directed mutagenesis at two positions. Although preliminary results indicate that the capacity of the mutants to bind to putative receptors on the plasma membrane of susceptible cells was unaffected, toxicity in vivo was reduced by 70-80%. The role of the highly hydrophobic segment exposed at the N terminus of the toxin after proteolytic activation was investigated by substituting two aspartate residues for phenylalanine and valine located adjacent to each other in the centre of this segment. The toxicity of the resulting mutant protein was only 40% of the unmutated toxin but again preliminary results suggest that binding to putative receptors was unaffected. These results suggest that regions close to the N-terminus of this and similar toxins may play an important role in the membrane insertion event which is believed to follow receptor recognition. PMID- 2332160 TI - Intraspecific sequence variation in the mitochondrial genome of rainbow trout (Oncorhynchus mykiss). AB - We examined the sequence of a 2214 base pair HindIII fragment from the mitochondrial genome of six rainbow trout. The fragment encodes four proteins and two tRNAs. Sequences for two fish from a single locality were identical. Those from separate localities differed by from 1 to 7 nucleotide substitutions. Of 13 variable sites, 12 were synonymous and 1 led to a conservative amino acid substitution. Transitions accounted for 12 of the 13 variants. In contrast to interspecific comparisons (Thomas and Beckenbach. 1989. J. Mol. Evol. 29: 233 245), the intraspecific divergence estimates based on sequence are less than those estimated from restriction fragment analysis, suggesting a complex, dynamic process for the accumulation of variation in the mitochondrial genome. PMID- 2332161 TI - Chromosomal organization of the amplified esterase B1 gene in organophosphate resistant Culex pipiens quinquefasciatus Say (Diptera, Culicidae). AB - In Culex pipiens quinquefasciatus from California, high resistance to organophosphorus insecticides is due to an increased production of the detoxifying esterase B1 resulting from a 250-fold amplification of the structural gene. The chromosomal organization of this amplified gene was studied by in situ hybridization techniques. Esterase B1 gene copies were found to be clustered on a single chromosome, tentatively identified as chromosome II. PMID- 2332162 TI - Differential action of restriction endonucleases on chromosomes prepared for light and electron microscopy. AB - Whole mounted chromosomes from the L929 mouse cell line were digested on grids with HinfI and AluI restriction endonucleases and studied by electron microscopy. Results show differences in the pattern of bands obtained in a marker chromosome when compared with those previously reported by light microscopy with the same restriction endonucleases. These differences suggest that the accessibility of restriction sites on chromosomes may be modulated by preparatory methods for chromosome analysis. PMID- 2332163 TI - Characterization of expressed meiotic prophase repeat transcript clones of Lilium: meiosis-specific expression, relatedness, and affinities to small heat shock protein genes. AB - The inserts of plasmid cDNA clones for transcripts showing meiotic prophase specific expression show cross reassociation to varying degrees of intensity with one another. These clones were recovered from a cDNA library made from Lilium microsporocyte poly(A)+ RNA. RNA-dot and Northern-blot analyses indicate that these clones represent transcripts specific to the meiotic prophase interval in microsporocytes. The transcripts appear to constitute the most abundant class of meiosis-specific poly(A)+ RNAs. At least two subgroups can be distinguished by examining cloned transcripts from genes of this expressed meiotic prophase repeat (EMPR) sequence family. Members of each subgroup have similar although not identical restriction maps and show relatively high but varying fidelities of DNA cross reassociation between members. However, consensus restriction maps of the two subgroups are largely dissimilar and, except at low stringencies, cross reassociation is readily detected only at restriction fragments from a particular conserved internal segment. The DNA sequence of a representative EMPR clone has been determined, and the inferred peptide product has been found to show extensive sequence homology to that of a small heat-shock gene of Glycine max, particularly in the conserved region. Alignment of the sequences for the conserved regions of two EMPR subgroup representatives with the soybean sequence suggests that selection has acted to conserve similar blocks of amino acids in this area. These observations suggest that a major portion of the transcripts produced during the apparently unrelated processes of meiosis and heat shock in higher plants are derived from related gene sequences encoding similar products. PMID- 2332164 TI - Sulfur-rich proteins of Chlamydia trachomatis: developmentally regulated transcription of polycistronic mRNA from tandem promoters. AB - RNA was extracted at various times from cells infected with Chlamydia trachomatis serovar L1. Northern-blot analysis showed that transcription of the CrP gene encoding the 60-kDa cysteine-rich outer membrane protein (CrP) produces a temporally controlled polycistronic mRNA. Primer extension analysis indicated the presence of tandem promoters separated by 66 nt with transcriptional start points (tsp) located 577 and 643 nt upstream from the start codon of the mature 60-kDa CrP. Nucleotide (nt) sequencing of this region revealed a small open reading frame (SORF) with coding potential for an 88-amino acid protein containing 13 cysteine residues. This SORF is transcribed as both a polycistronic 2300-nt mRNA together with the CrP gene, and as a separate 480-nt mRNA. Analysis of the upstream sequences, around the tsp for these mRNAs, revealed the presence of three inverted repeat structures that might act as binding domain(s) for a regulatory protein. PMID- 2332165 TI - A highly efficient electroporation system for transformation of Yersinia. AB - The various pathogenic Yersinia species are not readily and efficiently transformed by classical methods. For this reason, the electroporation technique was applied for genetic transformation of these species. Using optimal conditions, we were able to transform the six Yersinia strains studied with the two most widely used groups of plasmids: pSU2718 (a pACYC184 derivative) and pK19 (a pUC19 derivative). Only Yersinia enterocolitica (Y. e.) serotype 0:8 gave poor results (less than 5 x 10(2) transformants/microgram) DNA). Electrical transformation of the other species resulted in high efficiencies, up to 10(5) transformants/microgram DNA for Y. e. serotypes 0:3 and 0:9, 10(6) for Y. pseudotuberculosis and 10(7) for Y. pestis. The results varied for each strain with the type of plasmid used. Neither the introduced foreign plasmid nor the resident 72-kb virulence plasmid underwent detectable deletions. Transformation was most efficient with supercoiled DNA, decreasing by one and four orders of magnitude for relaxed circular and linearized plasmids, respectively. The ability to easily and efficiently transfer plasmid DNA via electroporation will greatly facilitate the application of recombinant DNA technology for direct cloning and analysis of significant genes into Yersinia. PMID- 2332166 TI - Gene duplication in the evolution of the two complementing domains of gram negative bacterial tetracycline efflux proteins. AB - The resistance of Gram- bacteria to the broad-spectrum antibiotic tetracycline (Tc) results from energy-dependent drug efflux mediated by the tet gene product, the cytoplasmic membrane Tet protein. Amino acid (aa) sequences deduced from total tet nucleotide sequences of three different resistance determinants (classes A, B and C) indicate that the protein products [Tet(A), Tet(B), and Tet(C)] share a common ancestor. Hydropathic analysis of Tet sequences predicts twelve transmembrane segments in each protein, with six occurring in each half of the molecule. More importantly, the linear distributions of these segments in the N- and C-terminal halves are nearly identical, suggesting that the two halves of each Tet protein are related by a process of tandem gene duplication and divergence. Indeed, a variable but significant conservation of sequence was detected among the N- and C-terminal halves for all possible comparisons of the three proteins. Such conservation was not observed within other prokaryotic integral membrane proteins or when other prokaryotic proteins were compared to Tet halves. Similarity, both in sequence and in predicted transmembrane structural organization, strongly suggests that a common ancestor of Tet(A), Tet(B), and Tet(C) arose by duplication of a gene reading frame specifying a transmembrane protein of approximately 200 aa residues. The two halves of Tet proteins correspond to the two domains, alpha and beta, which have distinct, complementary roles in Tc efflux. Nevertheless, selective constraints to function in the cytoplasmic membrane have apparently led to maintenance of similar patterns of secondary structural organization in these complementary domains. PMID- 2332167 TI - Molecular analysis of an alcohol dehydrogenase-encoding genomic clone (adh2) from rice. AB - An alcohol dehydrogenase-encoding gene was isolated from a rice genomic library. The coding region was sequenced, and the gene was identified as adh2. The nucleotide sequence of this gene contains an open reading frame which is interrupted by nine introns. Sequences that are important for eukaryotic gene expression, e.g. the TATA box, polyadenylation signal, intron/exon junction and putative splicing branch sites, are found in the expected locations in the rice adh2. A sequence related to the hexanucleotide core of regulatory elements identified in anaerobically induced plant genes is also present in the 5' region of the rice adh2. PMID- 2332168 TI - A highly repeated retropseudogene-like sequence in DNA of the redbreasted merganser (Mergus serrator). AB - Two highly repeated nucleotide sequences (RBMI and RBMII) cloned from an EcoRI digest of DNA of the redbreasted merganser (Mergus serrator) account for approx. 5 to 10% of the DNA of M. serrator and the closely related Mergus merganser. Complete DNA digestion of seven members of the Mergini with EcoRI produces distinct, relatively species-specific patterns of a few high-Mr (greater than 1.5 kb) fragments of RBMI-like material. In such digests RBMII forms ladder-type patterns with monomers of approx. 200 bp. The sequence of a cloned 2.6-kb RBMI fragment from M. serrator contains several extended (up to 70 bp) and modified poly(dA) sequences, two open reading frames in opposite orientation to the longest poly(dA) sequence and two direct 10-bp repeats suggesting that RBMI is a rearranged retropseudogene-like element. PMID- 2332169 TI - Characterization and sequence of a mouse hsp70 gene and its expression in mouse cell lines. AB - A heat-inducible member of the mouse hsp70 gene family has been isolated and characterized. The gene, hsp70.1, has a primary transcript of 2.8 kb before and 3.1-3.5 kb after polyadenylation. It includes a 645-nucleotide (nt) 3' nontranslated terminus and a 225-nt 5' leader. The leader sequence is unusual in that it contains a 33-nt triple tandem repeat element proximal to the ATG codon. As expected, a single open reading frame encodes a 642-amino acid (aa) 70-kDa protein with 95% aa homology and 91% nt homology to a human hsp70 gene. While there is no homology through the 5'- and 3'-nontranslated regions, the human and mouse hsp70 gene promoters can be aligned to give 65% homology. Of three mouse cell lines studied, two expressed the 3.1- to 3.5-kb mRNA during heat shock. One line also expressed an additional, smaller, 2.6-kb hsp70 mRNA transcribed from a separate gene(s). Mouse erythroleukemia cells were unresponsive to heat shock, with neither hsp70 RNA being induced by heat shock. These results suggest that cell lineage has a major influence on the cellular response to heat shock and that the response is not universal in all cell types. PMID- 2332170 TI - Structure of gene mts1, transcribed in metastatic mouse tumor cells. AB - Different oncogenes are implicated in the genesis of tumors. However, little is known so far about the genes which are activated at the latest stages of tumor progression. While studying two genetically related mouse lines, highly metastatic CSML-100 and nearly nonmetastatic CSML-0, we have cloned the cDNA of the gene, mts1, which is specifically expressed in different metastatic cells. The gene contains an open reading frame of 101 amino acids and shows homology with a family of Ca2(+)-binding proteins. Here, we present data on the structure of a 17-kb genomic clone of mts1 with surrounding sequences. The gene contains two introns and three exons. The mts1 upstream region has been cloned in a plasmid containing the cat gene. The results of transient expression of the mts1 cat plasmid in NIH3T3 cells indicate the presence of a transcription regulator of mts1. PMID- 2332171 TI - Structural organization of the hCTLA-1 gene encoding human granzyme B. AB - Cytotoxic T lymphocytes (CTLs) and natural killer/lymphokine-activated cells produce granzymes, a family of serine esterase proteins located in cytoplasmic granules. These might be involved in different cytotoxic pathways. We report the structural organization of the human gene encoding granzyme B (hCTLA-1). A 4.75 kb genomic DNA fragment containing all the sequences of granzyme B-encoding cDNA clones has been sequenced. The gene is composed of five exons and four introns. A comparison with the genomic organization of murine CCP1/CTLA-1 showed very similar structure and a 76% nucleotide homology in the coding sequences. This suggests that both genes may have a common ancestor. No typical regulatory element was detected in the 1160 bp upstream from the ATG start codon. The detection of a second locus related to hCTLA-1 is also described. PMID- 2332172 TI - A satellite DNA family from pollock (Pollachius virens). AB - We have cloned and sequenced a highly reiterated EcoRI fragment of DNA from pollock (Pollachus virens). The EcoRI repeat is 200 (+/- 5) bp long, A + T-rich (65%) and exhibits a high degree of sequence conservation among representative members. It comprises 13% of the pollock nuclear DNA with a copy number of 5 x 10(5) per haploid genome. Partial digestion of pollock DNA with EcoRI or Hinf1, which cleaves within the repeat, followed by blot hybridization to a cloned repeat sequence, produced a ladder of hybridising bands indicating a tandemly arrayed organisation for the EcoRI repeat. Longer range periodicities, revealed by restriction endonuclease digestion, are superimposed on the tandem array. PMID- 2332173 TI - Protoplast fusion in microtiter plates for expression cloning in mammalian cells: demonstration of feasibility using membrane-bound alkaline phosphatase as a reporter enzyme. AB - Protoplast fusion is a method for directly transferring cloned DNA from bacteria to mammalian cells at high efficiency. Here, we have used membrane-bound alkaline phosphatase as a reporter enzyme in a miniprotoplast fusion assay. This work demonstrates the principle that large numbers of protoplast fusions can be done simultaneously and successfully, to assay for an activity encoded by an expression vector. The technique described here circumvents key hurdles to expression cloning. This method does not require a highly sensitive assay or a way of separating a rare expressing cell from the mixture of transfected cells containing other transfected genes. With a strong promoter, the protein encoded by the undiluted transfected cDNA should be produced at at least as high a level as it is endogenously produced in the cell from which its activity was first detected. Reference clones are stored, avoiding the need to separate out the cells that are successfully transfected; this also avoids the need to repurify the DNA from the transfected cell. Because of the use of microtiter plates, it is likely that such a method could be partially automated for many types of assays. PMID- 2332174 TI - Isolation by polymerase chain reaction of a cDNA whose product partially complements the ultraviolet sensitivity of xeroderma pigmentosum group C cells. AB - A xeroderma pigmentosum (XP) cell line from complementation group C has been complemented to attain ultraviolet (UV) resistance and DNA repair proficiency, by transfection with a human expression cDNA library, followed by selection to UV resistance. We now show that the transfected cDNAs can be rescued from cellular DNA of a secondary transformant by its in vitro amplification using expression vector-specific oligodeoxyribonucleotides as primers in a polymerase chain reaction. The amplified cDNAs were cloned into a mammalian expression vector. Their transfection into XP cells identified a single cDNA which specifically complemented the UV sensitivity of a group-C-derived cell line to the same partial UV-resistance levels exhibited by the transformant from which the cDNAs were rescued. PMID- 2332175 TI - Sequence of the putative low-density lipoprotein receptor-binding regions of apolipoprotein B in mouse and hamster. AB - The nucleotide sequences of 2.35 kb of the apoB genes (encoding apolipoprotein B) encompassing the low-density-lipoprotein receptor-binding domains from mouse and hamster, have been determined. The sequences are 87.6% identical at the DNA level and 84.6% identical at the protein level. The region is also highly conserved in pig and human. PMID- 2332176 TI - Protecting older women from their growing risk of cardiac disease. AB - Heart disease is the leading cause of mortality and a major cause of morbidity in women in the United States. Premenopausal and postmenopausal risk factors for cardiac disease must be reduced to protect women from this major health hazard. The main coronary risk factors for premenopausal women are hypertension, smoking, hyperlipidemia, obesity, and diabetes. Postmenopausal women have these risk factors in addition to a lack of estrogen. Most studies have shown that replacing estrogen in the menopausal woman reduces cardiovascular disease, probably by increasing HDL and decreasing LDL. PMID- 2332177 TI - Pigmented skin lesions in the elderly: considerations in the differential diagnosis. AB - Malignant melanoma affects all age groups, but its highest age-specific incidence is in the elderly. Early diagnosis depends on the ability to identify potential precursor lesions and subtle changes in melanocytic nevi indicative of malignant degeneration. Familiarity with the clinical appearance of the common benign pigmented lesions is essential to minimize unnecessary biopsy procedures. Certain clues aid the differential diagnosis and enhance early recognition, which is presently the most effective means of reducing both the morbidity and mortality from this most ominous of skin cancers. PMID- 2332178 TI - UTI: managing the most common nursing home infection. AB - Urinary tract infections (UTIs) are the most common type of infection in nursing homes. Asymptomatic bacteriuria, the most common form, requires no treatment. Symptomatic UTI requires treatment, but symptoms (acute deterioration in functional ability or mental status) may be nonspecific. Complicated UTI is more common in nursing home residents than in other populations. Immobility and the use of bedpans instead of commodes contribute to decreased bladder emptying and an increased potential for UTI. Poor perineal hygiene in many females in nursing homes also increases the potential for UTI. For this reason, obtaining urine for culture by catheterization rather than voided specimen should be the norm for female nursing home patients. PMID- 2332179 TI - Toward a new understanding of rheumatoid arthritis. PMID- 2332180 TI - Keeping an eye on older patients and their drugs. PMID- 2332181 TI - [Occupational medicine and prevention of occupational diseases in the People's Republic of China]. PMID- 2332182 TI - [Determining the leading occupational and non-occupational factors in the planning of priority measures for reducing the incidence of diseases with temporary disability]. AB - The research showed the possibility of using Kulback's informatory indices for distributing the qualitative properties connected with the morbidity levels with temporary disability among the workers of an instrument-making plant. Among the factors studied, the most informative were: marital state (K-7.2), psychological climate in the family (K-6.8), satisfaction with one's profession (K-5.3). Measures for optimizing personal life provide a complementary source of lowering morbidity with temporary disability. PMID- 2332183 TI - [Biological effect of brown coal dust on the bronchopulmonary system and immunocompetent organs (experimental morphological study)]. AB - Inhalation of the brown coal samples caused anthracosis with progressive growth in the postinhalation period and concomitant catarrhal-desquamative bronchitis, lymphoid tissue hyperplasia, emphysema, along with granuloma formation. The cases studied were marked with increased number and thickness of the argyrophile and reticuline fibres around the bronchi, vessels, granuloma and in the interalveolar septum. Changes were detected in the immunocompetent organs' state which might influence the homeostasis and the immune system. Complex cytomorphological investigation of the bronchopulmonary and immunocompetent systems can be applied to in biological studies of different aerosols. PMID- 2332184 TI - [Effect of the dust factor on the condition of the pulmonary neural elements in coal miners]. AB - The article deals with the influence of dust load on coal miners' health state, the quality characteristics of mine dusts and degrees of coniotic changes in the lungs affected as a result of the nervous elements' reactions. Described are the peculiarities of the chronic processes in the nervous system in mine workers affected with dusts. PMID- 2332185 TI - [Possible mechanisms of the development of osteopaties in patients with chronic lead poisoning]. AB - Osseous tissue conditions were studied against changing clinical manifestations of chronic intoxications with lead. In more than 50% cases, hypertrophic osteoporosis was revealed. 65% cases were marked with osteoarthrosis deformans of the elbow and knee joints. The contributors review the local and general hormonal mechanisms underlying osteopathy caused by lead intoxications. PMID- 2332186 TI - [Energy metabolism during short-term thermal adaptation]. PMID- 2332187 TI - [Problem of the incidence of occupational diseases in the Soviet Union and abroad]. PMID- 2332188 TI - [Comparative evaluation of standardized and special roentgenological methods in the study of the osteo-articular changes in the hands of moulders]. PMID- 2332189 TI - [Evaluation of the psychophysiological state of workers in metallurgical hot shops]. PMID- 2332190 TI - [Various characteristics of lipid metabolism in tungsten-processing industry workers in the Transbaikal region]. PMID- 2332191 TI - [Legal aspects of the activities of the sanitary-epidemiological centers in detection and investigation of occupational diseases]. PMID- 2332192 TI - Interactions of methemoglobin and green hemoprotein in chemiluminescent gels. AB - Peroxidation of luminol (5-amino-2,3-dihydrophthalazine-1,4-dione) catalyzed by human green hemoprotein (GHP) and bovine methemoglobin (MetHb) in gels composed of cross-linked bovine serum albumin was examined. The chemiluminescence (CL) was followed with a low-light intensity video camera and imaging system attached to a circularly polarized microwave guide (2450 MHz) for heating the samples from 24 degrees C to 37 degrees C. Steady-state CL was maintained in the gels for 10 min. The intensity of the CL varied with temperature. When combined with MetHb in the same gel, GHP inhibited CL of MetHb from 83.6% to 98.2% over a fiftyfold concentration range of GHP. Although MetHb/GHP combination gels were inhibited, they generated a 6.12-fold CL per degree C change compared to a 0.19-fold per degree C change for MetHb gels and a 0.31-fold per degree C change for GHP gels. The data suggest an interaction between GHP and MetHb that inhibits the CL reaction, is not interfered with by large amounts of albumin, and is partially reversed by heating. PMID- 2332193 TI - The protective role of neocuproine against cardiac damage in isolated perfused rat hearts. AB - The effect of neocuproine on cardiac injury was studied using retrogradely perfused isolated rat hearts in two experimental systems. In the first system, where hydrogen peroxide-induced damage was studied, neocuproine at the range of 40-175 microM provided protection at the level of 70-85%, as demonstrated by the reduced loss in the peak systolic pressure (P), in +dP/dt and in -dP/dt. In the second system, where ischemia/reperfusion-induced arrhythmias were studied, neocuproine (42 microM) provided a marked protection against cardiac injury as demonstrated by the lowering of the incidence in irreversible ventricular fibrillation, by decreasing the duration of ventricular fibrillation and by the concomitant increase of the duration of normal sinus rhythm, and by improving the post-ischemic recovery of P, +dP/dt and -dP/dt. Free radicals have already been implicated as causative agents in cardiac injury resulting from either hydrogen peroxide or ischemia followed by reperfusion. Additionally, iron and copper have already been shown to drastically exacerbate the injurious effects of free radicals. Thus, the results reported here with neocuproine, a highly effective chelator for both iron and copper, as well as with adventitious copper and with the combination of neocuproine and copper, are in accord with the mediatory role of transition metals in enhancing the deleterious effects induced by free radicals. PMID- 2332194 TI - Kinetic studies of four types of nitroheterocyclic radicals by pulse radiolysis. Correlation of pharmacological properties to decay rates. AB - The chemical properties of the nitro radical of four types of nitroheterocyclic compounds, nitrofurans, 2-nitroimidazoles, 4(5)-nitroimidazoles, 5 nitroimidazoles, having radiosensitizing and cytotoxic properties, have been studied by pulse radiolysis. The acid-base equilibria involving the nitro radical, the imidazole ring and some residues on the heterocycle have been determined. The pH-dependence of the rate of the disproportionation reaction of the nitro radical have been extensively studied. While the nitro radical derived from nitrofurans, 4- and 5-nitroimidazoles had a second-order decay, those of the 2-nitroimidazoles were found to decay through simultaneous first-order and second order processes. Intrinsic second-order rate constants of the decay of the radical species in its various acidic and basic forms, could be determined. The intrinsic rate constants that determine the overall decay rates in the physiologically important 6 to 7.5 pH-range could be related to the one-electron redox potential E7(1). The implication of such chemical properties to enzyme catalyzed reduction processes and to the mechanisms of radiosensitization and cytotoxicity of nitroheterocyclic compounds are briefly discussed. Pharmacological properties such as in vitro radiosensitization efficiency or metabolic reduction rates could be related to two of the nitro radical intrinsic disproportionation rates. PMID- 2332195 TI - The interaction of fish trypanosome culture forms with some lectins. AB - The interactions of fish trypanosome culture forms with 11 purified lectins were compared using the agglutination test in microwell plates. Altogether, ten stocks of ten different freshwater fish species were examined. Three basic types of cell lectin interactions were observed on the microscopical level. The strong agglutination of all stocks regardless their original host was found in the presence of Con A, PSA, RCA60, and RCA120, which implies the presence of relatively high amounts of sugar residues of D-mannose and D-galactose in the surface of culture forms of these parasites. Weak agglutinations of some stocks were observed in the presence of LCA, PNA, SBA, and WGA lectins, but their low intensity makes them not sufficiently reliable for stock characterization. The lectins UEA I, HPA, and PHA caused no agglutination. In conclusion, in case of unequivocal results no remarkable differences in the interactions of various stocks of trypanosomes culture forms with used lectins were observed. These results imply the high degree of similarity of their main cell surface saccharide structures. PMID- 2332196 TI - Double alteration of the small intestine in conventional and gnotobiotic piglets experimentally infected with the coccidium Isospora suis (Apicomplexa, Eimeriidae). AB - The pathogenicity of the coccidium Isospora suis was studied in 42 conventional and 26 gnotobiotic piglets at 1-13 days post infection (DPI). The prepatent period of the coccidium I. suis was 4.5-5 days. Only in one experiment in conventional piglets the prepatent period of 3.5 days was recorded. At least 9 days pathogenesis of I. suis was recorded during which double alteration of the small intestine occurred. The first alteration was found at 3-4 DPI. The second phase of alterative changes was observed at 8-9 DPI. In comparison with gnotobiotic piglets in conventional piglets clinical signs and pathological changes used to appear one day sooner but reparation and regeneration of alterative changes was quicker. In the first phase of the infection (3-7 or 8 DPI) the heaviest pathological changes were in the posterior jejunum. In the second phase of the infection (8 or 9-12 DPI) the heaviest changes were in the middle jejunum. In short period repeated lesions of mucosal barrier of the small intestine multiply the pathogenicity of I. suis and rank I. suis in front place among other enteropathogens of nursing piglets. PMID- 2332197 TI - Some remarks on the prevalence and species composition of hare coccidia. AB - In the period between autumn 1983 and winter 1985, 33 digestive tracts and 317 coprological samples of hares were examined. The prevalence of individual coccidian species was reported on the basis of the examination of both the digestive tracts and coprological samples. The following coccidian species were found: Eimeria babatica (with 26.4% prevalence in the season 1983/1984 and 31.1% in 1984/1985), E. europaea (21.2% and 30.3%), E. hungarica (6.5% and 7.6%), E. leporis (24.2% and 45.4%), E. macrosculpta (1.3% and 2.5%), E. robertsoni (36.8% and 29.4%), E. sculpta (6.9% and 13.4%), E. semisculpta (15.6% and 10.0%), and E. townsendi (67.1% and 74.8%), respectively. The species E. babatica, E. macrosculpta, and E. sculpta were recorded in Czechoslovakia for the first time. The oocyst morphology and location of coccidia in the digestive tracts of hares were studied. PMID- 2332198 TI - Additional records of nematode parasites from Papua New Guinea amphibians with a list of recorded endohelminths by amphibian hosts. AB - An examination of a small sample of four species of frogs (Cophixalus riparius, Phrynomantis humicola, Ph. stictogaster, Ph. wilhelmana) from Papua New Guinea yielded altogether 5 species of nematodes, 2 of them being new to science. These include: Cosmocercella phrynomantisi sp. n. (type host Ph. humicola), Spinicaudinae gen. sp., Parathelandros andersoni sp. n. (type host C. riparius), Oswaldocruzia bakeri, and Paracapillaria spratti. C. phrynomantisi sp. n. differs from congeneric species mainly in the length of spicules (0.180 mm) and the character, arrangement and number of caudal papillae in the male, while P. andersoni sp. n. is characterized mainly by the presence of four well developed spines on the male tail. Pseudocapillaria spratti is redescribed in detail and it is transferred to Paracapillaria as P. spratti (Moravec et Sey, 1986) comb. n. Capillaria combesi Chabaud et Knoepffler, 1985 is transferred to Amphibiocapillaria Moravec, 1982 and Capillaria petiti Justine et Bain, 1987 to Pseudocapillaria Freitas, 1959. A survey of the endohelminths (excluding Hirudinea) hitherto reported from New Guinea amphibians is presented. PMID- 2332199 TI - Electrophoretic analysis of gene-enzyme systems in Chabertia ovina. AB - In Chaberia ovina species an electrophoretic study of 15 loci of the following enzymes has been conducted: glucose phosphate isomerase, mannose phosphate isomerase, glucose-6-phosphate dehydrogenase, glutamate-oxaloacetate transaminase, superoxide dismutase, isocitrate dehydrogenase, hexokinase, adenylate kinase, malate dehydrogenase, malic enzyme, carbonic anhydrase and 6 phosphogluconate dehydrogenase. The genetic variability has been relatively high, with 40% polymorphism values noted, an 0.10 mean heterozygosity observed and an 0.17 mean heterozygosity expected. The greater part of the allele frequencies were not in Hardy-Weinberg equilibrium. PMID- 2332200 TI - A new genus of capillariids from birds, Tridentocapillaria gen. n. (Nematoda: Capillariidae). AB - A new genus of the family Capillariidae, Tridentocapillaria gen. n., has been established. A type species is Tridentocapillaria tridens (Dujardin, 1845) comb. n. Other species of this genus are T. eurycerca (Oschmarin et Parukhin, 1963) comb. n., T. parusi (Wakelin, Schmidt et Kuntz, 1970) comb. n., and T. javanensis (Wakelin, Schmidt et Kuntz, 1971) comb. n. The new genus is characterized by the presence of a trilobed pseudobursa formed by three processes, and a vulvar appendage is always present in females. The genus includes species parasitic in the intestine of birds of the orders Passeriformes and Piciformes. PMID- 2332201 TI - Visualization of chitin-protein layer formation in Ascaris lumbricoides egg shells. AB - The formation of chitin-protein layer in Ascaris lumbricoides egg-shells was studied using the method of chitin structures visualization by means of derivatives of stilbene-disulfonic acid (Blankophor, Bayer, FRG). Intensive formation of chitin structures in A. lumbricoides egg-shell occurred only in fertilized females in a very short portion of uterus from the site of connection of the oviduct with the uterus up to 25-30 mm distally, i.e. in the section forming about one fifth or less than one sixth of length of adult female uterus. Already 3 mm from the beginning of uterus there was a thin layer on the surface of the fertilized eggs which contained chitin detectable by Blankophor visualization, whereas the chitin-protein layer on the shells could not be demonstrated histologically. The thickness of this chitin-protein complex increased distally. At 25 mm from the beginning of uterus the chitin layer was already complete and its thickness did not increase any more. PMID- 2332202 TI - Three species of the hair follicle mites (Acari: Demodicidae) parasitizing the sheep, Ovis aries L. AB - Evidence of three distinct Demodex species parasitizing the sheep is given for the first time. A newly distinguished Demodex sp. is described, and diagnostic characters are compared for Demodex ovis Hirst, 1919, D. aries Desch, 1983, and Demodex sp. Information on prevalence, distribution in the tissues, and pathogenicity of these three Demodex species in 132 head of sheep in Czechoslovakia is presented, with a review of such data published to date. PMID- 2332203 TI - Occurrence of the tick Ixodes laguri Ol. on the territory of Czechoslovakia. PMID- 2332204 TI - First record of Avioserpens larvae (Nematoda) from the naturally infected intermediate host. PMID- 2332205 TI - First record of mite hypopi (Acaridae) on fleas from Czechoslovakia. PMID- 2332206 TI - Superficial adenocarcinoma of the oesophagus arising in Barrett's mucosa with dysplasia: a clinico-pathological study of 12 patients. AB - Superficial adenocarcinoma of the oesophagus is defined as carcinoma limited to the mucosa or submucosa regardless of lymph node status. Columnar epithelium lined lower oesophagus, now generally referred to as Barrett's oesophagus, is probably the main cause of adenocarcinoma in the lower oesophagus. Twelve cases of superficial adenocarcinoma arising in Barrett's oesophagus are presented. They were observed over a 6 year period and taken from a series of 50 cases of patients with Barrett's oesophagus and adenocarcinoma, a prevalence of 24%. Endoscopic diagnosis of malignancy was made in six patients. The initial biopsies showed an adenocarcinoma in six patients and some degrees of dysplasia in the other six patients. Prior to surgery, a histological diagnosis of adenocarcinoma was made in all twelve patients. In four patients the adenocarcinoma was confined to the mucosa, and in eight it extended to the submucosa. One patient had a metastatic lymph node. Ten patients are alive without evidence of tumour spread after a mean follow-up of 30 months. PMID- 2332207 TI - Hepatocyte inclusions of alpha 1-antichymotrypsin in a patient with partial deficiency of alpha 1-antichymotrypsin and chronic liver disease. AB - We present a case of chronic liver disease with selective and exclusive hepatocyte endoplasmic reticulum storage of alpha 1-antichymotrypsin in the form of granules, detected by specific immunohistochemistry at the light microscopy level and corresponding to material found in dilated endoplasmic reticulum of hepatocytes by electron microscopy. The patient had intermediate deficiency of alpha 1-antichymotrypsin. Thus, the hepatocyte accumulation of alpha 1 antichymotrypsin may indicate the presence of an export block resembling that of a closely-related protein, namely PiZ alpha 1-antitrypsin. It is proposed that hepatocyte storage of alpha 1-antichymotrypsin may be an expression of an inborn error of metabolism bearing the characteristics of endoplasmic reticulum storage diseases such as PiZ alpha 1-antitrypsin deficiency and hereditary hypofibrinogenaemia. PMID- 2332208 TI - Melanin production in black medullary thyroid carcinoma (MTC). AB - Melanin production by two medullary carcinomas of the thyroid is reported and discussed. In both tumours, melanin and calcitonin could be detected in the same cells. PMID- 2332209 TI - The pathological spectrum of desmoplastic infantile gangliogliomas. AB - A rare supratentorial neuroepithelial tumour in a 10-month-old girl is described. It was characterized by its voluminous size, a predominant leptomeningeal growth pattern with intense desmoplasia and divergent differentiation along astrocytic, neuronal and Schwann cell lines. The differential diagnoses are discussed with special reference to the recently described clinicopathological entity of desmoplastic infantile ganglioglioma. PMID- 2332210 TI - Myelosarcoma without acute leukaemia: immunohistochemical and clinico-pathologic characterization of eight cases. AB - Eight cases of myelosarcoma without acute leukaemia at time of diagnosis were reviewed and biopsies were immunostained using antibodies reacting with myeloid/monocytic markers. Initial tumour location included lymph nodes, paranasal sinuses, nasopharyngeal and/or orbital regions and other extranodal locations. Three cases developed acute myeloblastic leukaemia within 1-9 months. Diagnosis was correct in four of the cases, in the other cases a non-Hodgkin's lymphoma was initially diagnosed. Morphological examination showed a blastic but variable appearance of the tumours. In a few cases cytoplasmic granulation was present. Chloroacetate esterase was present in all cases. In paraffin sections cathepsin G. elastase or lysozyme were present in all cases except one. In frozen material from four of the cases, the myeloid markers CD 11c and CD 33 were present (all cases) and CD 13 and Ki M8 in 3/4 cases. PMID- 2332211 TI - Nucleolar organizer regions in gastric carcinoma and its precursor stages. AB - A silver technique for nucleolar organizer regions (AgNOR) was applied to sections from 156 gastric biopsies and gastrectomy specimens. These included normal controls, normal gastric mucosa from carcinoma-bearing stomachs, intestinal metaplasia types I and III, dysplasia and carcinoma. AgNOR counts gradually increased from normal, through intestinal metaplasia, to carcinoma. This finding supports the chronic atrophic gastritis-intestinal metaplasia dysplasia-carcinoma sequence concept for gastric carcinogenesis. Normal gastric mucosa was different from all lesions, including normal mucosa from carcinoma bearing stomachs. Significantly higher AgNOR counts were observed in tumours compared to all other lesions except dysplasia. Dysplasia differed from intestinal metaplasia type I but not from type III. Eighty-five per cent of metaplasia cases overlapped with carcinoma and 19% with normal controls. The spread of AgNOR values in intestinal metaplasia reinforces the concept that this lesion is a heterogeneous entity reflecting a dynamic and continuous process. The AgNOR technique may contribute to the assessment of the stage of evolution of 'borderline' lesions. PMID- 2332212 TI - Malignant sex cord-stromal tumour in a patient with the androgen insensitivity syndrome. AB - A malignant sex cord-stromal tumour that occurred in a 56-year-old patient with the androgen insensitivity syndrome is reported. Although hamartomas composed of sex cord cells are common in the testes of patients with this syndrome, unequivocal neoplasms of sex cord type are rare. The tumour described herein most closely resembled, but lacked the overall morphology of, a juvenile granulosa cell tumour, and Charcot-Bottcher filaments, indicative of Sertoli cell differentiation, were seen on electron microscopy. The features of the androgen insensitivity syndrome and the various tumours that have been reported in patients with this syndrome are briefly reviewed. PMID- 2332213 TI - Immunoglobulin classes in biopsies of autoimmune liver disease. AB - The immunological isotypes of plasma cell infiltrates in a series of consecutive liver biopsies from patients with chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC) were determined immunohistochemically. The plasma cell infiltrate was more pronounced in PBC than in CAH. IgA and IgG isotypes predominated in CAH, and IgM and IgG in PBC. The expected predominance of kappa light chains was observed in every biopsy in PBC. However, in 8/14 CAH biopsies the plasma cells were predominantly lambda isotype. Lambda predominance was significantly associated with the presence of serum autoantibodies. These findings would suggest that different mechanisms operate in the pathogenesis of these two autoimmune liver diseases. PMID- 2332214 TI - Intranodal myofibroblastoma presenting in the submandibular region: evidence of a broader clinical and histological spectrum. AB - Intranodal myofibroblastoma is an uncommon benign mesenchymal tumour of lymph nodes which was first described in May 1989. All the cases described to date have presented exclusively in the groin, a feature which has been regarded as distinctive. Two new cases are presented herein, both of which arose in the submandibular region of middle-aged females. Both lesions showed histological features marginally different from the cases originally described, which may reflect their different anatomical location. Immunohistochemical staining revealed positivity for muscle-specific actin (HHF 35), as previously described, and ultrastructural examination in one case confirmed the presence of myofibroblasts. The data presented suggest that this distinctive lesion has a broader clinicopathological spectrum than previously realised. PMID- 2332215 TI - Malignant peripheral nerve sheath tumour arising in a schwannoma. PMID- 2332216 TI - Malignant mixed mullerian tumour of the fallopian tube. AB - We report two cases of primary heterologous malignant mixed Mullerian tumour of the Fallopian tube. One of these was bilateral, a finding which, as far as we know, has not been reported before. PMID- 2332217 TI - Inflammatory pseudotumours of the spleen. PMID- 2332218 TI - Mucinous metaplasia in endometriosis of the bladder. PMID- 2332219 TI - Endoplasmic reticulum storage disease. PMID- 2332220 TI - Clear cell metaplasia of the breast. PMID- 2332221 TI - Cribriform endometrioid adenocarcinoma, not adenoid cystic carcinoma, of the endometrium. PMID- 2332222 TI - Outpatient electroconvulsive therapy: a cost-saving alternative. PMID- 2332223 TI - Utilization review: a house divided. PMID- 2332224 TI - Self-help groups for former patients: relations with mental health professionals. AB - Data from a national survey of 104 self-help groups for former mental patients were examined to assess actual and potential partnerships between these groups and mental health professionals. The groups' level of interaction with and attitudes toward professionals varied with the structure, affiliation, and service model of the groups. The majority were moderate "supportive" groups in which partnerships with professionals could occur but were problematic. Less common were radical "separatist" groups, with which professional partnerships were almost guaranteed to fail, and conservative "partnership" groups, with which partnerships were likely to succeed. Strong antipsychiatric attitudes throughout the mental patient movement suggest that mental health professionals who approach former-patient groups with narrow clinical conceptions of mental illness are likely to fail in establishing partnerships. PMID- 2332225 TI - The staff psychiatrist and the Joint Commission survey. AB - The psychiatrist on a hospital's medical staff has a major role in maintaining the quality standards established by the Joint Commission on Accreditation of Healthcare Organizations and in preparing for its accreditation survey. The authors review the medical staff's role in quality assurance activities, including development of clinical indicators, monitoring of clinical data, peer review of problems, and planning for improved care. Other areas of hospital operation requiring the attention of the medical staff are the functioning of the medical executive committee, hospital bylaws, and procedures for granting, denying, and amending clinical privileges. PMID- 2332226 TI - Team use of the Global Assessment Scale for inpatient planning and evaluation. AB - A cost-effective team adaptation of the Global Assessment Scale (GAS) is used on the admitting ward of a state hospital. At admission staff meetings and at weekly progress review meetings, each member of the multidisciplinary team independently provides a GAS rating for each patient. The mean of each set of ratings becomes the patient's current team GAS score. The scores for individual patients, the changes in the scores over time, and the average scores for the ward offer a method for objectively expressing the patients' levels of functioning. Reliability and validity data supporting the method are reported. The team GAS format serves planning, evaluation, and research functions for individual patients and for the ward as a whole. PMID- 2332227 TI - Patterns of service use and costs in model day hospital-in programs in Boston and Tucson. AB - Patterns of service use and costs in two similar model day hospital-inn programs for psychiatric patients in publicly funded hospitals in Boston and Tucson are compared. Implementation of the programs resulted in cost savings at both sites, although mean annual costs per patient were much lower in Tucson than in Boston. Compared with patients at the Boston site, patients in Tucson had more admissions but shorter stays and fewer days in the program during a 12-month follow-up period. Site-specific differences in the programs, in local practice patterns, and in state mental health funding levels may have influenced cost differences. PMID- 2332228 TI - Teaching chronic psychiatric inpatients to use differential attention to change each other's behaviors. AB - For nine months, all psychiatric inpatients who came into a 26-bed coed adult ward in a state hospital were taught the principles and application of differential attention to determine whether it could be a used as a significant therapeutic modality on a ward for chronic patients. In two half-hour classes each week, patients were encouraged to praise each other's desirable behaviors and ignore undesirable ones. Thirteen patients were measured for improvement of 21 behaviors that included self-care, adaptive, and social skills. The target behaviors doubled in frequency as a result of the intervention, and praise improved the performance of target behaviors whether the praise was prompted by staff or not. Men and women improved equally from the intervention. Behaviors that were consistently prompted by patients improved more than self-initiated behaviors. Patients who volunteered to be helped by peer praise appeared to benefit the most. PMID- 2332229 TI - Diagnostic results of psychiatric evaluations of state police officers. AB - Twenty-six state police officers referred by their department or self-referred were evaluated by a university department of psychiatry over a 28-month period. The most common primary diagnosis was adjustment disorder, followed by substance abuse and personality disorder. Sixteen of the officers were assessed to be psychiatrically capable of returning to duty; concurrent outpatient treatment was recommended for most of them. The most challenging cases for evaluation were those involving psychiatric symptoms after trauma on duty, behavioral manifestations of personality disorder, and substance abuse. PMID- 2332230 TI - The changing organization of inpatient psychiatric care in general hospitals. PMID- 2332231 TI - HIV-related risk factors in acute psychiatric inpatients. PMID- 2332232 TI - Reunions of former inpatients on a psychiatric unit. PMID- 2332233 TI - Pimozide and tricyclics. PMID- 2332234 TI - Smoking by outpatients. PMID- 2332235 TI - Social work's PIE system. PMID- 2332236 TI - Discrepancy in HMO data. PMID- 2332237 TI - Housing for the homeless. PMID- 2332239 TI - Control of regional blood flow by endothelium-derived nitric oxide. AB - The regional hemodynamic consequences of inhibiting vascular endothelial nitric oxide generation with NG-monomethyl-L-arginine (L-NMMA) were studied in conscious Long-Evans rats. Experiments were carried out in groups of chronically instrumented rats with intravascular catheters and pulsed Doppler probes to monitor regional blood flow. L-NMMA (0.3-300 mg/kg) caused a dose-dependent, long lasting (5-90 minutes), and enantiomerically specific increase in mean blood pressure and also caused bradycardia. The increase in blood pressure was accompanied by a dose-dependent and long-lasting vasoconstriction in the internal carotid, mesenteric, renal, and hindquarters vascular beds that could be attenuated, in a concentration-dependent manner, by L-arginine but not by D arginine. In contrast, L-arginine did not affect the pressor or vasoconstrictor effects of vasopressin. These results indicate that nitric oxide production by vascular endothelial cells contributes to the maintenance of blood pressure and to the control of the resting tone of different vascular beds in the conscious rat. PMID- 2332238 TI - Prostaglandin H2 may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat. AB - The present experiment was performed to identify endothelium-derived contracting factor produced by acetylcholine stimulation in the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The rings of the thoracic aorta were obtained from age-matched SHR and WKY rats, and changes in isometric tension were recorded. The relaxant responses to acetylcholine in the aortic rings from SHR were significantly weaker than those from WKY rats. The relaxant responses to acetylcholine were significantly enhanced by pretreatment with a cyclooxygenase inhibitor (indomethacin) or thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708) in aortic rings from both SHR and WKY rats. A thromboxane A2 synthetase inhibitor (OKY-046) did not affect the acetylcholine induced relaxation in the aortic rings from SHR or WKY rats. In the organ bath solution, after acetylcholine stimulation, prostaglandin E2 and 6-keto prostaglandin F1 alpha concentrations increased but not prostaglandin F2 alpha and thromboxane B2 concentrations. Exogenous prostaglandin H2, a stable analogue of thromboxane A2, and prostaglandin F2 alpha induced contractions of the SHR rings at a lower concentration than prostaglandin E2, prostaglandin D2, and prostaglandin I2. These contractile responses to various prostaglandins were markedly inhibited by pretreatment with ONO-3708. A prostacyclin synthetase inhibitor did not affect the relaxant responses to acetylcholine in the SHR rings. These results show that endothelium-derived contracting factor is produced and released by acetylcholine stimulation not only in the aorta of SHR but also in those of WKY rats and suggest that prostaglandin H2, a precursor of the released prostaglandins, is a strong candidate for endothelium-derived contracting factor produced by acetylcholine stimulation. PMID- 2332240 TI - Arterial baroreceptor reflex modulation of sympathetic-cardiovascular adjustments to heat stress. AB - The purpose of this study was to determine if the arterial baroreceptor reflexes modulate the sympathocirculatory responses to acute heat stress. To address this, arterial pressure, heart rate, mesenteric and renal blood flow velocity (Doppler flow probes), arterial plasma norepinephrine, and colonic temperature were measured before and during whole body heating (42 degrees C ambient temperature) in groups of conscious, unrestrained rats with (sham) or without (sinoaortic deafferentation) intact arterial baroreceptor reflexes. Heating was stopped when a colonic temperature of 41 degrees C was attained. Baseline levels of arterial pressure were similar in the two groups, whereas heart rate was elevated in deafferented versus sham-operated rats (p less than 0.01). The increases above baseline for both arterial pressure (73 +/- 4 vs. 27 +/- 2 mm Hg) and heart rate (127 +/- 10 vs. 33 +/- 5 beats/min) were threefold to fourfold greater at the end of heating in the deafferented versus the sham group (p less than 0.01). Declines in mesenteric and renal blood flow were similar in the two groups during heating; however, deafferented rats had greater increases in both mesenteric and renal vascular resistance (p less than 0.05). Plasma norepinephrine was elevated at baseline in deafferented versus sham rats and increased in both groups during heating (p less than 0.01). The magnitude of the increase in plasma norepinephrine from baseline to 41 degrees C was fivefold greater in the deafferented versus the sham rats (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332241 TI - Hyperthermia: a hyperadrenergic state. PMID- 2332242 TI - Body fat and its distribution in relation to casual and ambulatory blood pressure. AB - This study was undertaken to evaluate the associations of body fat and its distribution with casual and ambulatory blood pressure in nonobese men. One hundred and thirty-five normotensive or mildly hypertensive (but untreated) men employed at three work sites were studied. Casual blood pressure was measured at the work site at initial screening and on a second occasion by a nurse. Ambulatory blood pressure was measured noninvasively for 24 hours on a workday and analyzed as work, home, and sleep blood pressure measurements. Anthropometric measurements included height, weight, and waist and hip circumferences. Blood pressure was highest while at work; home blood pressure was higher than screening blood pressure or nurse blood pressure, and sleep blood pressure was lowest. Weight and both waist and hip circumferences (but not their ratio) were all significantly correlated with screening, nurse, and sleep blood pressures but not with work or home blood pressures. Stepwise regression analysis showed that waist circumference was the best overall predictor of blood pressure. We suggest that in situations where blood pressure is the dependent variable, correlations with other variables may be closest for "basal" measures of blood pressure and may be obscured by the effects of daily activities on blood pressure. PMID- 2332243 TI - Hypertension: a lifetime of mining salt. PMID- 2332244 TI - Urinary Mycobacterium fortuitum infection. AB - Mycobacterium fortuitum, a common saprophyte usually found in water and soil, can also be isolated from sputum and gastric secretions of healthy carriers. Under certain conditions, significant clinical infections due to M. fortuitum do occur. Urinary tract infections are rarely caused by atypical mycobacteria. This report describes a urinary tract infection caused by M. fortuitum in a 73-year-old patient treated with corticosteroids for bronchial asthma, who was successfully treated with ofloxacin. PMID- 2332245 TI - Efficacy of sulbactam in an in vitro model of mixed aerobic/anaerobic infections. AB - Bacterial interactions in mixed infections may interfere with antimicrobial therapy. The in-vitro efficacy of ampicillin alone, combination sulbactam/ampicillin, and metronidazole was studied. Strains of Bacteroides fragilis, Escherichia coli, and Enterococcus faecalis, alone and in association, were tested by means of a broth dilution method. Minimal bactericidal concentrations (MBC) of ampicillin for B. fragilis 74 in association with E. coli 68 were up to 16-fold higher than for B. fragilis 74 alone (256 compared to 16 mg/l), but only 2-fold higher for sulbactam (5 mg/l)/ampicillin (0.5 and 0.25 g/l). Association of B. fragilis 45 and E. faecalis 186 increased ampicillin MBC of E. faecalis 186 from 2 to 16 mg/l, but the combination sulbactam/ampicillin restored activity of ampicillin. In association with E. faecalis, metronidazole MBCs of B. fragilis increased up to 64-fold. Strains of E. faecalis and E. coli were able to destroy 10 mg/l metronidazole within 8 to 20 h. The present experiments demonstrated effectiveness of sulbactam/ampicillin to inhibit beta lactamases of associated pathogens. Destruction of metronidazole by E. faecalis lends additional support to the use of the combination in aerobic/anaerobic infections including E. faecalis. PMID- 2332246 TI - Concentration of ciprofloxacin in non-functional gallbladder mucosa after single dose intravenous administration. PMID- 2332247 TI - Prognostic significance of cerebrospinal fluid adenosine deaminase in acute bacterial meningitis. PMID- 2332248 TI - Selection of antibiotics for treatment and prophylaxis of staphylococcal infections in cystic fibrosis patients. AB - Susceptibility in vitro of 179 staphylococcal strains from 107 cystic fibrosis patients against 31 antibiotics indicates that only teicoplanin, vancomycin and netilmicin were active against all strains. The use of betalactam antibiotics is impaired by 11.7% of methicillin-resistant strains. The bactericidal kinetics of cephalexin and flucloxacillin as determined in a pharmacodynamic model demonstrates the killing of strains resistant to cephalexin (MIC 8 mg/l to 32 mg/l) by flucloxacillin. For the rational selection of antistaphylococcal antibiotics for cystic fibrosis patients, both the MIC of the isolates and the concentration of the antibiotics in cystic fibrosis patients have to be considered. PMID- 2332249 TI - The role and prevalence of Gardnerella vaginalis in anaerobic vaginosis. AB - 310 cases of anaerobic vaginosis and 80 asymptomatic females were studied for the detection of various organisms from their genital specimens. The main complaint of the symptomatic cases was vaginal discharge. Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginalis. Bacteroides species, anaerobic cocci and Gardnerella vaginalis were detected. The frequency of detection of all except C. albicans was less in pregnant than non-pregnant women. However, the prevalence of anaerobes and G. vaginalis was significantly lower in both the symptomatic and asymptomatic pregnant than the non-pregnant women. G. vaginalis showed mutualism with anaerobic bacteria and was not isolated as a pure culture in any of the cases. It appears that G. vaginalis, like anaerobes, has variable prevalence rates and is under the influence of local physiological and hormonal factors. This organism does not appear to have a primary pathogenic role, but assumes a secondary role in association with non-sporing anaerobes in the pathogenesis of anaerobic vaginosis. PMID- 2332250 TI - No-fault-compensation, patient guarantee, peer review committees: the Swedish experience. AB - Complaints from patients about dental treatment are on the increase internationally and especially in the USA. The Swedish system for dealing with patients' complaints embraces four different pathways which are described in this paper. One of those is a no-fault-compensation system, which is wholly separate from a procedure under the control of the Swedish licensing authority which deals exclusively with assessing professional negligence. A further, voluntary procedure for dealing with patient complaints is mediated by the Swedish Dental Association and its branches. The paper analyses the type and number of complaints and their assessment under the different procedures. PMID- 2332251 TI - Comparison of the dental health of 12-year-old schoolchildren living in Athens and Glasgow. AB - In 1987 studies of the dental health of 12-year-old children in Athens and Glasgow were linked to allow comparison. Standardized examiners used the same methodology and criteria in the two studies and the data were also analysed by socio-economic background. Mean DMFT in Glasgow was 2.91, compared with a mean of 4.71 in a 1984 study. Mean DMFT for Athens 12-year olds was 2.41, in 1987, showing that irrespective of social background, they had reached the WHO Global Goal of 3.0. In Glasgow, 12-year olds from the deprived areas still fell far short of this target. As Greece's new National Health Service begins, a plea is made for the commissioning of National Dental Surveys, to assist monitoring and planning. PMID- 2332252 TI - Dental survey: patient attitudes in Jordan. AB - A questionnaire was used to assess the attitude of family members in Jordan to the state of their teeth, their personal oral hygiene and their acceptance of dental care. The questions were formulated to provide information without the need for dental examination. In industrial societies there is evidence of a reduction in the rate of dental decay whereas in countries such as Jordan the reverse is true. Consideration of this trend, in combination with the results of this survey, provides a strong indication that instruction in oral hygiene must be given together with increased facilities for treatment. PMID- 2332253 TI - Critical issues of ageing: the dentist as a supervisor of the general health of the elderly. AB - The importance of the dentist's role in monitoring the general health of the ageing patient is described and its value is stressed. The quality of life and the health of an elderly patient is very closely linked with oral health, whilst the reverse is also true. The use of oral photography is described in this age group as an aid to diagnosis, review of possible pathological changes, patient motivation and as an educational resource. PMID- 2332254 TI - Teeth for life: oral disease prevention in research and practice. AB - All branches of dentistry have benefited in recent years from the rapid advances made in scientific research. Caries has been reduced in industrialized countries thanks to the combined efforts of epidemiologists, chemists, experimental and clinical scientists, identifying fluoride and refining fissure sealants. Genetic engineering may be pointing the way towards a possible caries vaccine as well as enhancing regimens against periodontal diseases. In addition research has provided advances in preventing and treating soft-tissue pathologies. Over the next 20 years a research and action programme aims to eliminate toothlessness in the USA. PMID- 2332255 TI - Promoting oral health: guidelines for dental associations. AB - Dental associations throughout the world face many new challenges. For example, many industrial countries confront the potential of excess manpower to meet current demands, while developing countries try to cope with scarce resources to control existing and increasing disease levels. This guide is intended to facilitate the development of oral promotion programmes in both situations. In industrialized countries, an oral health promotion programme should increase awareness and interest among consumers, thus facilitating the conversion of unmet need to demand. In developing countries, the oral health promotion guidelines demonstrate ways to extend resources to meet a broader base of need. In all countries, oral health promotion can demonstrate the benefit of self-care and emphasize the consumer's responsibility for personal health. Dental associations enjoy a long history of promoting oral health, yet developing a coherent programme or realizing the results of these efforts can sometimes be disappointing or frustrating. The guide is organized around a recommended sequence of activities: policy formation and dissemination; planning group; information gathering; goal setting; strategic planning; implementation; and evaluation. This document presents guidelines, not recipes. Given the range of economic, social and health needs of the Federation Dentaire Internationale member countries, a recipe would be inappropriate. These guidelines can be tailored to the needs of your association based on the oral health needs of your population. They can be used to determine new or modified policies, to assess long- and short-term goals, to monitor progress and to educate the membership. Case studies derived from actual experiences of dental associations as they planned and analysed their efforts to promote oral health are presented. This information is included to highlight different approaches as well as problems encountered. The case studies illustrate various parts of the planning implementation and evaluation process, while the text should serve as a comprehensive review of all these components. PMID- 2332256 TI - Children's attitudes toward elderly individuals: a comparison of two ethnic groups. AB - The present study investigated the attitudes of Indian and American children toward elderly people. The "Children's Attitudes Toward the Elderly" questionnaire was used to measure how children perceived elderly people. Chi square analyses indicated that children of Indian origin gave behavioral responses more often than affective or cognitive ones, while American children were more affective in their responses to questions about their interactions with elderly individuals. The results indicated that Indian children though born and raised in America were encouraged to follow the traditional values of their families' culture. Further research should include actual observations of children from different ethnic backgrounds interacting with elderly people. PMID- 2332257 TI - Reminiscence, adaptation, and social context in old age. AB - It is commonly believed that reminiscence is adaptive in late life, but the sparse research on this topic has produced mixed results. This article suggests that one reason for inconsistent findings is the failure to consider social contexts. Interview data from three subgroups of residents of two retirement communities (widowed men, widowed women, and single women; N = 43) revealed sharp differences in the relationship between key aspects of reminiscence and two measures of adaptation (life satisfaction and self-esteem). For widowed men, elaboration of memories, life reviewing, and high importance of others were associated with positive adaptation, but the reverse was true for widowed women. Single women were intermediate, but those who had high peer contact were most similar to the adaptive pattern of the widowed women. Widowed men with high peer contact were most different from the widowed women. Several explanations for these differences are considered, including gender-role differences, life-course continuity, and the social composition of the retirement communities. PMID- 2332258 TI - The influence of stress and coping on family caregivers' perceptions of health. AB - Family members are increasingly assuming a caregiving role for their frail elders. This role, which is added to their other responsibilities, competes for time and attention and may generate stressful situations. Previous research established that stress may have both adaptive and maladaptive effects on individuals. This study examines the extent to which caregivers perceive their situations as stressful, how they cope, and the associated influences of stress and coping on perceptions of their own health. The aim is to identify stressful aspects of caregiving and ways of coping that may be maladaptive for caregivers, placing them at risk for illness and disease. PMID- 2332259 TI - Measuring locus of control in elderly persons. AB - Confirmatory factor analysis was used to examine the appropriateness of using with elderly persons Levenson's multidimensional locus of control (LoC) scale that measures beliefs in Internal Control (I), Control by Powerful Others (P), and Chance (C). Data were obtained from elderly individuals in Florida and Texas and reformulated to allow cross-validation at each step in a series of model evaluations. Results indicated that Levenson's three-factor specification of control was not a valid representation of the samples' responses. A model that specified the elimination of eleven unreliable items and the formation of a new external control factor that was based on the remaining C and P items provided an adequate fit to the data for both samples. The failure to confirm Levenson's three-factor structure poses a construct-validity and measurement-equivalence problem when making age-based comparisons of LoC scores. PMID- 2332261 TI - Prenatal care in Finland: from primary to tertiary health care? AB - Traditionally, the Finnish prenatal care system has been based on special maternity centers outside hospitals. In recent years, however, the use of hospital outpatient clinics has increased. The purpose of this study was to describe the use of the clinics and to see whether clinics serve as an addition or as an alternative to maternity centers. We used several different data sources (statistics, documents, interviews, questionnaires). The main source was data on visits for all women who gave birth in Helsinki in a five-week period in 1987. The content of care and means of care delivery differ between clinics and maternity centers. Clinics are technologically and provider-oriented without continuity of care. Clinics are not just referral centers for high-risk mothers; at least half of pregnant women visit them. Ultrasound screening is an important reason for use of the clinic. Background characteristics as well as the outcome of pregnancy were similar among women visiting a hospital clinic a maximum of one time (low users), two to three times, or four times or more (high users). Standardizing for the length of gestation, high users made fewer visits to maternity centers than did low users. Hospital clinic care now seems to replace care in maternity centers, and we found a weak trend toward a pluralistic prenatal care. PMID- 2332260 TI - Should we abolish the private health insurance industry? AB - Health care financing can be based on one of two conflicting principles: health care as a right versus the insurance principle. The former assures equal access to care for all people regardless of income, while the latter requires each grouping in society to pay its own way. In the United States, health financing has utilized both principles, with employer-sponsored group health insurance approximating health care as a right. However, the insurance principle is increasingly eroding this right. In five major areas, the private health insurance industry has serious flaws: it has contributed to health care inflation; it wastes billions in administrative and marketing costs; it is unfair to many groups in society; it has undermined the positive features of health maintenance organization reform; and it has far too much political and economic power. In order to establish health care as a right as the guiding principle of U.S. health care financing, the private health insurance industry and the insurance principle should be abolished. PMID- 2332262 TI - The chemical jungle: today's beef industry. AB - In the absence of effective federal regulation, the meat industry uses hundreds of animal feed additives, including antibiotics, tranquilizers, pesticides, animal drugs, artificial flavors, industrial wastes, and growth-promoting hormones, with little or no concern about the carcinogenic and other toxic effects of dietary residues of these additives. Illustratively, after decades of misleading assurances of the safety of diethylstilbestrol (DES) and its use as a growth-promoting animal-feed additive, the United States finally banned its use in 1979 some 40 years after it was first shown to be carcinogenic. The meat industry then promptly switched to other carcinogenic additives, particularly the natural sex hormones estradiol, progesterone, and testosterone, which are implanted in the ears of more than 90 percent of commercially raised feedlot cattle. Unlike the synthetic DES, residues of which can be monitored and use of which was conditional on a seven-day preslaughter withdrawal period, residues of natural hormones are not detectable, since they cannot be practically differentiated from the same hormones produced by the body. The relationship between recently increasing cancer rates and the lifetime exposure of the U.S. population to dietary residues of these and other unlabeled carcinogenic feed additives is a matter of critical public health concern. PMID- 2332263 TI - Mechanization, the labor process, and injury risks in the Canadian meat packing industry. AB - During the 1980s, Canada's major manufacturing industries experienced considerable financial restructuring and technological transformation, largely in response to recessionary pressures. At the same time, the rate of lost-time injuries in Canadian manufacturing rose steadily. This article explores the relationship between these sets of factors. The meat packing industry has been selected as a case study of the interaction between industrial organization, the labor process, and the risk of workplace injuries. The authors suggest that the following factors have contributed to high and rising injury rates in the meat industry during the 1980s: consolidation into a smaller number of large, highly specialized, and mechanized plants; deteriorating labor relations in the face of falling profits; and an intensified labor process stressing line speedups and a growing risk of repetitive strain injuries. These observations are supported by a detailed analysis of the relationship between the labor process and workplace injuries at one packing plant considered typical for the industry. PMID- 2332264 TI - Abortion policy and women's health in developing countries. AB - The World Health Organization estimates that almost half a million women in developing countries die in pregnancy and childbirth every year. Unsafe induced abortion is responsible for perhaps one-quarter of these deaths. In this article, the author reviews the legal, medical, and social contexts in which women in developing countries resort to clandestine abortion. Despite intensified international concern with reducing high rates of maternal mortality and morbidity, national policy makers and participants at international conferences on maternal health--with a few important exceptions--have not recommended that safe, legal services for terminating unwanted pregnancies be offered as an essential element of basic reproductive health care. United States international policy on funding abortion-related activities in maternal health and family planning programs is especially restrictive. A new policy approach is clearly needed if unacceptably high rates of maternal morbidity and mortality in many countries are to be reduced. PMID- 2332265 TI - The role of the social condition of women in the decline of maternal and female mortality. AB - The objective of this article is to study the changes that have occurred in the mortality pattern of women of fertile age in Spain throughout the 20th century, the significance of maternal mortality in the development of this pattern, and the other causes of death that have contributed most to such changes. Female mortality has most often been approached from the perspective of the genetic differences from males--particularly from the sexual-biological, basically reproductive, aspect--without considering other possible (social) differences. We have studied the female mortality pattern from the double incline of date of death (period) and of date of birth (cohort). Using the mortality theory of competing risks as our basis, we excluded in turn maternal mortality and mortality due to tuberculosis from overall mortality, and analyzed the transformations produced in the mortality pattern. Our results show that maternal mortality alone cannot be held responsible for the excess female mortality of the 1910s and 1920s, or for the mortality pattern among women of fertile age during the first half of this century. We suggest that the social discrimination against females from infancy has been responsible for most of the differences observed in mortality patterns. PMID- 2332266 TI - Tribunal on the policies of the International Monetary Fund and the World Bank, West Berlin, September 26-29, 1988: verdict. Permanent Peoples' Tribunal. AB - At the request of the American Association of Jurists, the Permanent Peoples' Tribunal was called upon to consider violations of international law of the self determination of peoples by the International Monetary Fund and the World Bank, as well as to make proposals for change. The Tribunal declared the request to be admissible, in accordance with Article 3 of the Statutes; therefore, the International Monetary Fund and the World Bank were informed, in application of the provisions of Articles 14 and 15. The Tribunal convened in West Berlin, September 26-29, 1988. Presented here is the report of the Tribunal, including its verdict and proposals for action. PMID- 2332267 TI - Editorial misconduct in Science. PMID- 2332268 TI - DNA content of juvenile granulosa tumors determined by flow cytometry. AB - Juvenile granulosa tumors (JGT) often exhibit worrisome morphologic features, yet usually behave in a benign fashion. Thirteen JGT were examined by flow cytometric analysis of paraffin material to determine if DNA content and cell kinetics are related to prognosis. The patients ranged in age from stillborn to 16 years. Unilateral salpingoophorectomy was the most common therapy. Eleven patients with follow-up were free of disease. Marked nuclear atypia was evident in three cases, and high mitotic counts were observed in six, but only marked atypia correlated with DNA content. Flow cytometry revealed that 46% of the JGT had abnormal DNA content and increased average growth fraction. The neoplasms with the highest DNA indices were found predominantly in postmenarchal girls. JGT may exhibit abnormal DNA content, nuclear atypia, and numerous mitoses, yet behave benignly. DNA flow cytometric studies of higher stage JGT are warranted. PMID- 2332269 TI - Serous psammocarcinoma of the ovary and peritoneum. AB - We report 11 cases of serous psammocarcinoma, a rare variant of serous carcinoma characterized by massive psammoma body formation and low-grade cytological features. The patients ranged in age from 36 to 76 (mean of 57) years. The tumors were stage three in every case (three stage IIIA, seven stage IIIB, and one stage IIIC). Eight of the patients had ovarian psammocarcinomas with ovarian tumors measuring 5-22 (mean of 11) cm in diameter; the other three patients had primary peritoneal psammocarcinomas. The surfaces of the ovarian tumors were smooth and intact in seven of eight ovarian psammocarcinomas. Cysts were present in six of eight ovarian tumors, and the solid portions were typically gritty or granular. Necrosis was not seen. Microscopically there was destructive invasion of ovarian stroma or vascular invasion in the ovarian tumors; the extraovarian tumor implants were invasive of intraperitoneal viscera in five cases. The epithelium was arranged in small nests with no areas of solid epithelial proliferation, and at least 75% of the epithelial nests were associated with psammoma body formation. No more than moderate nuclear atypicality was identified in any case. No mitotic figures were found in 10 of the tumors, with a single mitotic figure identified in the other tumor. Follow-up data for more than 1 year was available for six patients, with two patients lost to follow-up and three patients followed without evidence of recurrence for less than 1 year. One patient died of tumor 6 1/2 years after presentation, and five patients were alive without evidence of recurrent tumor 3-10 (mean of 8.3) years after presentation. Although based on a small number of cases, these data suggest that the clinical behavior of psammocarcinoma more closely resembles that of borderline serous tumors than of serous carcinomas of the usual type, following a protracted course and being associated with a relatively favorable prognosis. PMID- 2332270 TI - Tubal metaplasia of the uterine cervix. AB - Eleven cases of tubal metaplasia of the uterine cervix are presented. These are characterized histologically by architecturally normal endocervical glands containing ciliated or clear cells, nonciliated cells, and intercalary or peg cells, resembling normal tubal mucosa. Transitions from normal to ciliated epithelium within a single gland are frequently seen. Eight of these cases involved endocervical glands near the squamocolumnar junction, and six showed tubal metaplasia along the overlying surface epithelium. Superficial and (in one case) deep endocervical glands were involved. No correlation was found between the presence of tubal metaplasia and the degree of inflammation of the cervix or the presence or extent of squamous metaplasia. Immunohistochemically, the epithelium of tubal metaplasia was negative for carcinoembryonic antigen in five cases studied. In situ squamous carcinoma and a variety of benign glandular lesions, such as microglandular hyperplasia, mesonephric remnants, and endometriosis, were concurrently identified. Two cases also accompanied tubal metaplasia in proliferative and hyperplastic endometria, and tubal metaplasia was seen in the lower uterine segment in five cases. We emphasize that, as with other types of metaplasia, the main significance of recognizing this lesion in the cervix is in not confusing it with early endocervical glandular neoplasia. PMID- 2332271 TI - Placental site trophoblastic tumor: with features between an exaggerated placental site reaction and a placental site trophoblastic tumor. AB - Chorionic villi, whose presence in cases of trophoblastic disease is normally used to exclude both a choriocarcinoma and placental site trophoblastic tumor (PSTT), were present in the initial uterine curettage specimen of a trophoblastic tumor. The lesion shared morphologic features of both an exaggerated placental site reaction and a PSTT. There was infiltration of the posterior wall of the uterus by small clusters and isolated cells which had a prominent affinity for vessels and resembled a usual placental bed reaction. There was, however, deep involvement of myometrium with extension to the cervix, and the condition persisted for 5 months after uterine evacuation. Because different treatment is entailed, identification of this lesion as a tumor of nonvillous trophoblast is also of great importance in a region where the more usual forms of trophoblastic disease represent a declining but not infrequent event. When products of gestation are examined, the possibility of a PSTT should be considered and the clinician alerted if there is a suggestion of excessive intermediate trophoblastic activity, regardless of the presence of chorionic villi. While this may result in the unnecessary followup of some cases, it would permit, with the aid of serial beta-hCG and HPL levels, the earlier detection of PSTTs. PMID- 2332272 TI - Immature teratoma of the ovary grade 3, with karyotype analysis. AB - The relationship between dermoid cysts and immature teratomas has been investigated by study of gross and microscopic data. Karyotypes with banding analysis, already numerous for dermoid cysts, have recently been obtained for immature teratomas. This grade 3, Stage III immature ovarian teratoma was of probable premeiotic origin, as evidenced by chromosome heteromorphisms identical to those of the host cells. The relationship of this pattern to that of other immature teratomas and dermoid cysts is discussed. PMID- 2332273 TI - Phylogenetic relationships of Cryptosporidium determined by ribosomal RNA sequence comparison. AB - Reverse transcription of total cellular RNA was used to obtain a partial sequence of the small subunit ribosomal RNA of Cryptosporidium, a protist currently placed in the phylum Apicomplexa. The semi-conserved regions were aligned with homologous sequences in a range of other eukaryotes, and the evolutionary relationships of Cryptosporidium were determined by two different methods of phylogenetic analysis. The prokaryotes Escherichia coli and Halobacterium cuti were included as outgroups. The results do not show an especially close relationship of Cryptosporidium to other members of the phylum Apicomplexa. PMID- 2332274 TI - Saurian malaria in Kenya: epidemiological features of malarial infections in lizard populations of the West Pokot District. AB - During investigations into the prevalence of malarial parasites among lizards in the West Pokot District in Kenya, 179 lizards comprising eight species were caught. Examination of the Giemsa-stained smears made from their blood showed that 34 lizards were infected with Plasmodium species. Fifteen lizards were infected with a single species of Plasmodium and 19 carried multiple infections, the maximum, in four lizards, was four species. There were 19 combinations of parasite infections. Seventeen Plasmodium species were identified, the commonest being P. icipeensis. Only two of the eight lizard species were infected: the skink Mabuya striata and the agamid Agama agama. Eight of the Plasmodium species infected both; another eight species infected M. striata only but three of these have been described from different lizard families elsewhere in Africa. P. robinsoni infected A. agama only, although it was first described from another lizard family in another part of Africa. The epidemiological significance of these results is discussed. PMID- 2332275 TI - Development and survival of infective larvae of Haemonchus contortus and Trichostrongylus colubriformis on pasture in a tropical environment. AB - A trial to determine the seasonal pattern of egg hatching and larval survival on pasture was carried out in representative wet and dry zones of Fiji. Fourteen plots were established on parasite-free pasture at each of two sites. One plot at each site was contaminated every month with faeces from naturally infected goats containing a known proportion of Haemonchus contortus and Trichostrongylus colubriformis eggs. Pasture was sampled at regular intervals after contamination and infective larvae identified and counted. Larvae of both species developed throughout the year in the wet zone but development was more sporadic in the dry zone. Larval counts generally declined to below detectable levels within 9 weeks of contamination between September and March but longevity increased during the cooler weather from April to August. The comparatively short larval survival times noted in this experiment may present opportunities for manipulation of parasite population dynamics in the wet tropics. PMID- 2332276 TI - Effect of benzimidazole drugs on tubulin in benzimidazole resistant and susceptible strains of Caenorhabditis elegans. AB - An in vitro assay was used to determine efficacy and if side resistance was present to benzimidazole anthelmintics tested against Caenorhabditis elegans after selection with albendazole. Side resistance was present to all the benzimidazoles tested, except for oxibendazole and parbendazole. At a concentration of 1 mM, all of the drugs, except thiabendazole, were effective in killing 100% of the albendazole susceptible worms. Tubulin from albendazole resistant and susceptible C. elegans was isolated and run on polyacrylamide gels. Western blots with anti-tubulin antibody showed that the albendazole resistant strain had an altered tubulin. Electron microscopy of albendazole-treated drug resistant worms showed microtubules throughout the intestinal cells. Microtubules were not observed in albendazole-treated drug susceptible worms. PMID- 2332277 TI - Anhydrobiosis in the infective juveniles of Trichostrongylus colubriformis (Nematoda: Trichostrongylidae). AB - The infective juveniles of Trichostrongylus colubriformis can survive exposure to 0% relative humidity after desiccation at higher relative humidities. During rehydration there is a lag phase before recovery. The infective juveniles are thus capable of anhydrobiosis. Removal of the sheath does not affect desiccation survival but does affect the duration of the lag phase. Morphological changes during the lag phase are described. The appearance of birefringence in the muscle cells during the anomalous shrinkage which occurs during the lag phase is considered to reflect physiological changes necessary for the recovery of normal muscle function. PMID- 2332278 TI - Analysis and comparison of cercarial emergence rhythms of Schistosoma haematobium, S. intercalatum, S. bovis, and their hybrid progeny. AB - In identical experimental conditions, the three schistosomes of the terminal spined egg group (S. haematobium, S. intercalatum and S. bovis) showed significant differences in their cercarial shedding patterns. The cercariae of the F1 hybrids, obtained by experimental crosses between these three species, showed the same circadian emergence rhythm (with one peak) as the cercariae of the parental species. However, the mean shedding time of these hybrid parasites (12:14 +/- 1 h 34 min for S. haematobium x S. intercalatum; 09:58 +/- 1 h 24 min for S. haematobium x S. bovis; 08:57 +/- 1 h 19 min for S. bovis x S. intercalatum) was always in advance to the one of their parental species (13:51 +/- 2 h 04 min for S. haematobium; 13:59 +/- 1 h 55 min for S. intercalatum; 10:09 +/- 2 h 04 min for S. bovis). These results are compared with those obtained from crosses between schistosomes with lateral spined eggs, and from crosses between intraspecific chronobiological variants of S. mansoni. They corroborate the genetic determinism of the cercarial emergence of schistosomes. Moreover, such significant differences between the hybrids and their parents in the times of cercarial emission may be of value in the epidemiological research and characterization of naturally occurring hybrids. PMID- 2332279 TI - Quantitative evaluation of intracellular degradation in Entamoeba invadens. AB - A quantitative study on digestion of erythrocytes by Entamoeba invadens was attempted. Trophozoites of the IP-1 strain were fed red blood cells for 30 min, and subsequently phagocytosis was stopped by means of osmotic shock; post phagocytosis incubations for up to 15 h were made in order to evaluate intracellular digestion, after staining the red blood cells with benzidine. Eighty-two per cent of trophozoites were capable of phagocytosing erythrocytes, containing an average of 5.5 erythrocytes per amoeba. Erythrocyte digestion within amoebae was shown by loss of benzidine-stainable material and proceeded with a first-order kinetics, with a t1/2 approximately 7 h. Within 15 h there were no amoebae containing erythrocytes. The procedure described may be useful for the evaluation of intracellular digestion in other Entamoeba species. PMID- 2332280 TI - Molecular basis of hyperlipidemia in golden hamsters during experimental infection with Ancylostoma ceylanicum (Nematoda:Strongylidae). AB - An infection of golden hamsters with Ancylostoma ceylanicum, a hookworm parasite, induced profound hyperlipidemia, particularly hypertriglyceridemia, and the effect was directly related to the degree of infection. A significant increase was also noticed in serum cholesterol and phospholipid levels. The appearance of lipoprotein-X, an abnormal low density lipoprotein, was detected in the serum of hookworm-infected animals. The hyperlipidemia was further characterized by an increase in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) with a concomitant decline in high density lipoproteins (HDL). Decreased lipolytic activities, especially triglyceride lipase, in hepatic tissue and induction of lipolytic activities in intestine and adipose tissues indicated mobilization of fats from adipose and jejunum with a defective removal of triglyceride-rich lipoproteins in hepatic tissues. Accumulation of lipids in liver and depletion in adipose tissue supported these results. The derangement may have a significant effect on host parasite interaction and is an important pathophysiological feature occurring during experimental ancylostomiasis. PMID- 2332281 TI - Structure, stability and species interactions in helminth communities of wood mice, Apodemus sylvaticus. AB - The helminths of the alimentary tract of wood mice, Apodemus sylvaticus, were studied at two sites over a 33-month period. Nine helminth species were recovered regularly. All but one was absent for at least 1 month. Monthly samples from these helminth communities were more similar to samples taken in the following month than to samples taken at progressively greater intervals up to a year. Helminth communities at both sites, however, had cyclical elements. Comparison of mean similarity indices for helminth faunas from 33 monthly samples and those from data sets generated by four null models suggests that observed values did not differ from a model where relative abundance of each species was determined randomly with specific maxima of abundance and species absences based on observed data. Loss of helminth species may decrease measurements of community stability based on relative abundance while persistence of abundant species increases stability. Helminth faunas in samples of A. sylvaticus from six localities taken at the same time of year at 5-year intervals indicated that some changed radically while others remained virtually unchanged. The considerable variation in helminth communities from different localities was not related to proximity or gross habitat characteristics. Nematospiroides dubius, Corrigia vitta and Capillaria murissylvatici were important in discriminating between the parasite faunas at different sites. Abundance of Syphacia stroma varied considerably between spatial surveys reflecting differences in host population dynamics in the 2 years. The present report and data from elsewhere in Ireland suggest that species composition of the helminths associated with A. sylvaticus may be stable over a wider geographical scale. There were neither strong nor consistent positive or negative interactions between pairs of helminth species. It is concluded that the stability characteristics of this parasite community, in terms of species composition and relative abundance, are the product of the population biology of independent parasite species rather than interspecific interactions. Variation in the role of competition in parasite communities is discussed. PMID- 2332282 TI - Potential of a soluble tetrazolium/formazan assay for the evaluation of filarial viability. AB - Using female Acanthocheilonema viteae we have investigated the bioreduction of the tetrazolium reagent XTT (2,3-bis(2-methoxy-4-nitro-sulphonyl)-5 [(phenylamino) carbonyl]-2H-tetrazolium hydroxide). Unlike the formazan formed by other tetrazolium salts, that derived from XTT readily diffuses out of A. viteae in vitro. Formazan formation can therefore be quantified by direct absorbance reading of the incubation medium, eliminating the need for a DMSO solubilization step. Optimum assay conditions involved a 4 h incubation, in the presence of the electron coupling agent phenazine methosulphate (PMS). Repeat 4 h incubations with XTT-PMS were well tolerated by worms for 5 consecutive days. This confirmed the low toxicity of XTT formazan and its usefulness in the semi-continuous assessment of filarial viability. In comparison to our previously reported MTT (3 (4, 5 dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide)-reduction assay XTT-PMS reduction showed comparable drug sensitivity and accuracy, however XTT PMS appears to be at least 10-15 times less efficiently reduced by A. viteae females. A possible application of the XTT assay using female Onchocerca volvulus is discussed. PMID- 2332283 TI - Relative distribution of glutathione transferase, glyoxalase I and glyoxalase II in helminths. AB - Glutathione transferase, glyoxalase I and glyoxalase II activities were not evenly distributed among the major helminth groups. Intestinal cestodes and digeneans had higher glutathione transferase activity than parasitic nematodes. High glyoxalase II activity was found in cestodes and digeneans but no glyoxalase I was detectable. Glyoxalase I and II were both detected in nematodes. These results are discussed in relation to the enzymes' suggested role in protection against secondary lipid peroxidation products. PMID- 2332284 TI - Experimental infection of mice with Toxocara canis larvae obtained from Japanese quails. AB - The migration and distribution of Toxocara canis larvae in the tissues of Japanese quails, infected orally with 5 x 10(3) infective eggs, were studied, as well as the re-infectivity of these larvae in mice, inoculated with 50 larvae obtained from the liver of these quails. Post-infection, the highest concentrations of larvae were found to be present in the liver of quails while only a few migrated to other tissues like lungs, heart, muscle and brain. The migration and distribution of the larvae in the tissues of mice were studied by necropsy on days 6 and 12 post-infection. On both days the highest number of larvae, 11 and 10, were recovered from the carcase followed by six and seven from the leg muscles and four and eight from the brain, respectively. A few larvae were recovered from the liver, lungs and viscera. This implies that the larvae had a special affinity for the muscle and brain tissue of mice, unlike in the quails. The role of these larvae in relation to paratenism is discussed. PMID- 2332285 TI - Rapid technique for cryopreservation of Echinococcus multilocularis metacestodes. AB - Cysts of E. multilocularis were minced to prepare a crude homogenate and after addition of glycerol at a final concentration of 10%, cryopreservation was performed at a rate of 1 degree C min-1 in a controlled-rate freezer. The aliquots were subsequently stored in liquid nitrogen. All 22 isolates tested were successfully cryopreserved and their viability maintained. PMID- 2332286 TI - Papers presented at the 36th International Psychoanalytical Congress. August 1989, Rome. PMID- 2332287 TI - Analysis without apparent resistance. AB - With this addition to the slender literature of self-revelations by psychoanalysts, the author also makes what may be his final contribution to psychoanalysis. An episode of hypomania during a visit to his birthplace, Vienna, triggered a dream whose elucidation allowed him to recover a primal scene and complete a self-analysis begun 65 years earlier. Shortly thereafter, a stroke left him hemiplegic and forced the author to confront the final stage of a productive life. After describing a range of adaptations to age and failing health, he explores the role hypomania played in his reconciling with the inevitability of impending death. Analysis of the contending forces also deepens our understanding of the transformations the creative process undergoes in advanced age, a topic the author leaves for younger hands to perfect. PMID- 2332288 TI - Beyond semantics: a clinical and theoretical study of isolation. AB - Theories of Freud, Piaget, Fonagy and Kristeva have been drawn on to argue that the concept of isolation should not be restricted to a delimited defence mechanism associated with obsessional/compulsive neurosis, as is the usual psychoanalytic conception. From a semiological point of view isolation may be seen as a disturbance of the relationship between signifier and the signified embracing affective communication ranging from the most primitive bodily expression via sound and intonation to a semantic level where affects are expressed through the content of words and ideas. As affects isolated on a pre verbal level are deprived of expression on a semantic-symbolic level, they are not likely to be modified by content of interpretations alone. They can only be fully activated and brought into therapeutic dialogue through the quality of the speech sound of the analyst. PMID- 2332289 TI - Identification with a vengeance. AB - Identifications motivated by envy, in contrast to those based on admiration, a desire for affiliation or augmentation of the self, attempt to wreak vengeance on the object by denying it is as source. Instead of expressing the identity between subject and object, these identifications analogize to it, and then destroy the link. Envy is based on greed. Greed, unlike appetite, is insatiable. The ongoing desirability of the object makes it appear powerful and unforgettable--hence an object of ongoing envy. The question of what makes people unable to develop appetite is considered both from the point of view of the object and the possible innate unsatisfiability of the subject. PMID- 2332290 TI - Affect deficit: a vicissitude of the phenomenon and experience of affect. AB - Certain people are unable to discriminate, integrate and regulate their affective experience and their experience of pain. This disorder is related to alexithymia, la pensee operatoire and the dis-affected condition. Affect is best understood when a distinction is made between its somatic emergence and its subjective experience. The two patients described here were unable to provide language, mnemic symbol or associative meaning to their affective experiences. Their analyses revealed long histories of denial, disavowal and metaphorization of their somatic perceptions. The lack of validation of their somatic experiences contributed to their affect deficit condition. From a metapsychological perspective it is here hypothesized that in the above condition the body ego remains partially unintegrated from the sphere of the ego. PMID- 2332291 TI - Female genital anxieties, conflicts and typical mastery modes. AB - This paper focuses on the female experience of her own body, the unique anxieties that arise from the nature of the female genitals and the role of the female body in female development. Following Freud's theories of the importance of integrating body experiences in the development of psychic structures, the girl's body and her efforts to integrate it are seen as uniquely feminine. Three anxieties are described--access, penetration and diffusivity. These represent dangers to body integrity comparable to, but different from, boys' experience of castration anxiety. Not only do different genitals give rise to different anxieties, the different body experiences give rise to different modes of mastery (defence) shaping different character structures. While males can readily form discrete, concrete mental representations of their genitals, females cannot. While the boy can rely on direct sensory experience, the developing girl must rely on proprioceptive experiences, symbolization, and on other people to aid her in defining her elusive genital experience. This interpretation of the female genital experience provides a psychoanalytic framework for the object embeddedness long observed as part of the feminine character. PMID- 2332292 TI - Common ground: an analytic break and its consequences. AB - This is a clinical report of an analytical process which began under two years ago and in which there was a five-month break at the end of the first year. The break had been discussed in advance, but its effect on the treatment was no less intense on that score. The separation was experienced through feelings of pain with a heavy bodily quality by which she evoked the somatic memories of a heart operation she had when she was a baby. The analytic process seems to be allowing her to symbolize her painful experiences of separation and loss as well as the traumatic effects of her heart surgery. PMID- 2332293 TI - Psychoanalysis: the common ground. AB - This paper carries further the theme I developed in my presidential address in Montreal, 'One psychoanalysis or many?' where I discussed the issue of what holds us together as psychoanalysts sharing a common discipline and science despite our increasing theoretical diversity. My response was that our common ground rested in our shared clinical enterprise in our consulting rooms where we relate comparably to the immediacy of the transference-countertransference interplay with our patients. In this paper I reconsider these perspectives in the light of the specific responses to them, including in the six pre-published statements for the Rome Congress which was dedicated to this theme of exploring our common ground; and I then apply these conceptions in my own comparative assessment of the three plenary clinical presentations of the Rome Congress, drawn from the three major world regions of psychoanalytic activity and presented by adherents of three of the major metapsychological perspectives in our field, the ego psychological, the Kleinian, and the object relational. PMID- 2332294 TI - The psychoanalyst's methodological stance: some comments based on a response to Max Hernandez. AB - Our theories are to derive from empirical clinical findings. Their task is to order the data and broaden our perceptual scope. But often and unwittingly, we draw upon them to make leaps of inference about unconscious meaning, and bypass untold directions for which the model may not fit. Despite the fact that such super-imposition is generally decried, we are each of us vulnerable to using theory--experience-near or distant--to rationalize hidden assumptions and agendas, to lead our patients to 'truths' we presume we already 'know' to be present. The effort of this discussion has been to highlight this ubiquitous risk and to consider its implications for our psychoanalytic listening and concomitant methodology. PMID- 2332295 TI - Common ground: the centrality of the Oedipus complex. AB - An attempt is made to relate the severe restriction in the patient's life and in her mode of functioning within a long and difficult analysis to the internalization of, and partial identification with, primitive and damaged versions of the parental couple, which she experienced as threatened by, and hostile towards any form of vitality or creativity. When the expression of these more disturbing versions of the oedipal configuration could be recognized, tolerated and interpreted within the sessions, the patient's longings, jealousy and sexual wishes indicative of a more mature Oedipus complex became more readily available. This change was manifested in a different quality to the transference and in the way the patient became better able to integrate and use her own intellectual and emotional resources. PMID- 2332296 TI - The search for common ground. PMID- 2332297 TI - Vertigo and object relationship. AB - Vertigo appeared to me in analysis to be an expression of separation anxiety; we can observe the vicissitudes of the object relationship by way of the development of this symptom in the treatment. I identify different forms of vertigo according to the particular stage reached by the patient, from fusion-related vertigo via vertigo about being dropped, vertigo associated with aspiration, vertigo connected with the alternation of prison and escape and vertigo related to the attraction of the void, to competition-related vertigo which appears in an oedipal context. They correspond to different moments in the constitution of relational space: first, the two-dimensional world in which even the void is inconceivable; then, the sensation of the void manifesting a disavowal of the absence of relationship; next, the constitution of a three-dimensional space in which the patient initially feels carried by the object but then discovers that he can carry himself; and, finally, the constitution of the internal space which allows internalization of the feeling of 'buoyancy'. PMID- 2332298 TI - Common (under)ground in psychoanalysis: the question of a Weltanschauung revisited. AB - The aim of this paper is to suggest that, beneath the 'common ground' shared by different types of psychoanalyses, there is a common underground that is seldom discussed in psychoanalytic literature: the fact that any psychoanalysis has the potential of becoming a Weltanschauung or world-view. The roots of this fact in Freud's writings are discussed and some of the consequences of this transformation of psychoanalysis into Weltanschauung for psychoanalysis as science and movement are presented. PMID- 2332299 TI - On acting out. AB - The author sets out to compare her own ideas on the archaic matrix of the Oedipus complex, as opposed to the fully developed Oedipus complex, with Glover's conception of the different developmental stages of the mental apparatus in which historical priority is given to what he calls 'psychosomatic reactions' over later psychoneurotic symptoms. These former result in pure discharge, whereas the latter are characterized by meaningfulness. She also briefly tries to connect some of her views with those of Melanie Klein and Bion. PMID- 2332300 TI - Pathological organizations as obstacles to mourning: the role of unbearable guilt. AB - A patient is described who made moves to face his internal and external reality only to find that this put him in touch with an internal world in a horrific state. The horror resulted from his view of damaged and imprisoned objects which arose from the way his defences were organized into a pathological organization of the personality which controlled his objects with ruthlessness and cruelty. As he began to loosen his dependence on the organization and to face his internal situation, depressive anxieties became prominent and of these he found guilt particularly unbearable. In order to escape from guilt he retreated once more to the protection of the organization and it is this which prevented him mourning his lost objects. It is argued that it is in the process of mourning that lost parts of the self are regained and it is specifically this process which was interfered with by the pathological organization. PMID- 2332301 TI - The possibility of human freedom and its transmission (with particular reference to the thought of Bion). AB - In this paper I examine where Bion's theory of freedom fits within the traditional philosophical debate. I claim that the notion of freedom is the organizing centre of Bion's thought and that the traditional debate has focused with too great a concentration upon the will. I propose that underlying the workings of the will there is a fundamental substratum. This is governed either by the reaction model or by the response model. Freedom is coextensive with the latter mode of functioning but not with the former. The traditional debate needs to take this layer of personality functioning into account. PMID- 2332302 TI - Hemodynamic responses in rabbit tenuissimus muscle arterioles during local reduction in perfusion pressure. AB - Transverse (TR) and terminal (TE) arteriolar diameters and TR pressure were measured in the rabbit tenuissimus muscle during steady state reductions in perfusion pressure. An inflatable occluder was positioned on the abdominal aorta proximal to the bifurcation to alter perfusion pressure. In the control conditions, TEs exhibited highly regular cyclic activity (20 +/- 4 cpm). In contrast, TRs seldom exhibited regular vasomotor activity. Pressure reductions from 76 +/- 1 to 40-50 mm Hg caused no significant change in the observed hemodynamic variables. Reductions below this level caused proportional dilations of TRs and a change in vasomotion pattern of TEs; i.e. the fundamental frequency was unaltered, but periods without vasomotion increased in duration. At an arterial pressure of 30-40 mm Hg, vasomotion in the TEs completely disappeared. Pressure in the distal TR was autoregulated at 40 +/- 4 mm Hg until a threshold (40-50 mm Hg) was reached; thereafter TR pressure decreased in proportion to the arterial pressure decrements. These results suggest that the TRs are the last generation of arterioles involved in the autoregulation of microvascular pressure. Furthermore, the basic frequency and maximal amplitude of vasomotion in TEs are not affected by pressure reductions. PMID- 2332303 TI - The relation of the post-ischemic reperfusion impairment to the severity of ischemia in the tibialis anterior muscle of the rat. AB - Hyperemic volume flow rates were followed during 15 minutes of post-ischemic reperfusion in tibialis anterior muscle of the rat after 1, 2 and 3 hours of tourniquet ischemia using the 133Xenon clearance technique. Results showed a no reflow phenomenon after 2 and 3 hours of ischemia. There was a marked impairment in flow, seen immediately upon reperfusion as a reduction or abolishment of the initial peak of the normally brisk post-ischemic hyperemia. The impairment increased with increasing duration of ischemia. The range of maximal peak hyperemic flow rates was wide and median maximal peak flows were 43.1, 14.6 and 7.2 ml.min-1.100 g-1 after 1.2 and 3 hours, respectively. This reflow impairment was not caused by differences in arterial blood pressure at the start of perfusion or during the initial 2 minutes of perfusion. Venous hematocrit at the start of the reperfusion was not significantly different between the three groups. Total muscle water of 75.9% in control muscle increased to 79.7% after 3 hours of ischemia and 1 hour of reperfusion and reached a maximum of 85.7% after 5 hours of reperfusion, demonstrating that the no-reflow seen during the initial 15 minutes could not be caused by an increased tissue pressure due to rapidly developing reperfusion edema. Results indicate a microvascular hindrance in post ischemic reperfusion. PMID- 2332304 TI - Abstracts presented at the 13th annual meeting for Microcirculation e.V. Munich, F.R.G., November 24-25, 1989. PMID- 2332305 TI - Diode laser peripheral iridectomy. PMID- 2332306 TI - Lasers in ophthalmology. PMID- 2332307 TI - Effect of two rating formats in multi-disease ROC study of chest images. AB - ROC methodology has been expanded in recent years to include multi-disease experiments. To accommodate these changes, different rating formats, general or disease specific, can be used. No experimental data are available concerning the possible effects of the rating format on the results of these studies. We performed a multi-observer, multi-disease study in which 196 chest images were rated using a format where each disease was evaluated individually and one in which the cases were evaluated without scoring a specific disease. The results indicate that for our data set, the overall assessment of accuracy was not significantly affected by the study format used. Thus, in spite of the difficulties in selecting appropriate controls and the necessity of reassessing sample size considerations, the disease-specific format appears to produce an assessment of accuracy equivalent to that produced by the general format. This equivalence permits the use of the disease-specific approach since it more closely simulates the readers' true environment and is more appropriate for comparing imaging systems that may have a relative accuracy that is disease specific. PMID- 2332308 TI - Effect of observer instruction on ROC study of chest images. AB - Receiver-operating characteristic (ROC) analysis has been used in many medical imaging applications during the past decade. In order to ensure that reader confidence ratings are analyzable (well distributed to meet convergence requirements of curve-fitting algorithms) and meaningful (limit extrapolation of the data), many investigators train readers specifically for this purpose. No experimental data are available concerning the possible effects of such training on the results of ROC studies. We performed a multi-observer, multi-disease study in which 300 chest images were rated by four radiologists before and after they were trained to provide well-distributed confidence ratings. The results indicate that for our data set, reader and disease-specific accuracy was not significantly affected by the training process for interstitial disease and pneumothoraces. However, the accuracy of two readers was significantly affected for the detection of nodules (P less than 0.05), and the overall accuracy of one reader was significantly affected for the classification of normal versus abnormal images (P less than 0.01). Thus, in spite of the difficulties associated with the performance of ROC studies in a free-reading environment, one should carefully consider the possible effects of any intervention on the results prior to conducting ROC studies. PMID- 2332309 TI - Vascular tissue ablation by an erbium-YAG laser: a fiber-transmittable pulsed laser in the infrared range. AB - Vascular tissue ablation by an erbium:YAG laser of 2,940 nm was tested in-vitro with the application of increasing energies from 20 to 80 mJ per pulse. Effective ablation of normal vascular tissue, lipomatous atheromas and calcified plaques was achieved. Penetration depth was considerably diminished in the presence of calcifications. The lasered craters showed smooth surfaces and were regularly shaped. The solid state erbium:YAG, which is transmittable by fluoride fibers, offers theoretical advantages for laser angioplasty. PMID- 2332310 TI - Temporal changes in the oxidation state in in vitro blood. AB - The rates at which the paramagnetic compounds deoxyhemoglobin (Hb) and methemoglobin (MHb) form in vivo within an area of hemorrhage are unknown. The present experiment establishes the baseline concentrations and rates of change in paramagnetic hemoglobin concentrations, as well as the pH in normal heparinized and clotted human blood maintained in vitro at 37 degrees C under anaerobic conditions over 30 hours. There was a moderate increase in Hb concentration in normal heparinized blood (average increase was 15.5%, rate = 0.50%/hour) and a slight increase in MHb concentration in the heparinized blood and clots (average increase was 1.4%, rate = 0.044%/hour). A second experiment was done to verify the activity of the RBC systems responsible for maintaining the hemoglobin molecule in the reduced state. Conversion of MHb to Hb in these samples proceeded at a rate of 5.6%/hour. In a third experiment, blood from 11 normal subjects maintained at 4 degrees C 25 degrees C was analyzed for MHb concentration over the course of 28 days. The level of MHb formation remained in the range of normal for at least 11 days in all subjects. The authors conclude that at basal conditions created in vitro, the blood levels of both Hb and MHb remain at relatively low levels. Therefore, if the accumulation of Hb and/or MHb occurs in acute in vivo hematomas it must be driven by intrinsic tissue factors. PMID- 2332311 TI - A new method for investigating the sampling technique of fine needle aspiration biopsy. AB - An automatic sampler of fine needle aspiration biopsy for cytology (FNAC) is presented in order to study the technical performance of FNAC in vitro. The effects of the following sampling technique variables on specimen size and quality can be independently and quantitatively studied: suction force, duration and rate of increase of suction; count, frequency, amplitude and angle between the needle strokes; length, diameter, content and tip configuration of the needle; and target tissue. The efficacy of the sampler was compared with a manual method. It was demonstrated that the poor reproducibility of manual FNAC, combined with inaccuracy in following instructions regarding changes in sampling technique, render the manual system unsuitable for quantitative studies. The clumsiness of the manual system may be responsible for contradictory recommendations on how FNAC should be carried out. With the new in vitro sampler FNAC sampling can be studied under fully controlled conditions. PMID- 2332312 TI - CT features of renal cell carcinoma with emphasis on relation to tumor size. AB - Computed tomography (CT) is the current standard for diagnosing and staging renal cell carcinoma (RCC). Although general diagnostic guidelines exist, no large studies to date have delineated the CT features of RCC. We reviewed the CT appearances of 78 pathologically proven RCCs. Of the 61 RCCs larger than 50 mm (78%) there was imaging evidence of extrarenal spread (87%), intratumoral necrosis (61%) and differential growth rates within the tumor (64%). Tumors 50 mm or smaller often had a "benign" appearance with sharp, rounded margins (88%), homogeneous density (65%), and distinct interface with the kidney (82%). The significance of these lesions should not be underestimated. Although RCCs often showed transient marked enhancement after bolus contrast material injection (41%), during the infusion phase 97% were hypodense compared with the kidney regardless of tumor size. Calcifications were visible in 31% of RCCs. Although 22% of RCCs were predominantly cystic, none fulfilled all CT criteria of simple renal cysts. PMID- 2332313 TI - Approaches to increasing the ethical consistency of prior review of animal research. PMID- 2332314 TI - The radiologist's workstation. PMID- 2332315 TI - Teaching effectiveness in the radiology residency: a method of evaluation by residents. AB - Feedback from the residents can provide a valuable means to acknowledge good teaching by the faculty and a strong stimulus to improve weak teaching performances. As there were no published reports that describe a quantitative and systematic method to achieve this type of evaluation in the radiology residency, we developed a questionnaire of 62 elements that asked each resident to rate each member of the faculty and also to rate the program overall. Residents supplied a scaled response to each question using a rigid protocol that maintained anonymity. Several computer programs were written to process the large volume of data. Statistical evaluation of the data demonstrated that the method is capable of reproducing the residents' assessments with a high degree of accuracy and consistency. PMID- 2332316 TI - Gross anatomy instruction with diagnostic images. AB - A new module of instruction for diagnostic imaging with emphasis on cross sectional anatomy was developed within the existing course of gross anatomy for freshmen medical students. Two lectures introduced radiation protection, radiology history, and the basic principles of computed tomography, magnetic resonance imaging, ultrasound, and radiograph image production. Six radiographic anatomy correlation sessions allowed student-teacher interaction while studying viewbox images in a "hands on" fashion. Relevant exhibits complemented cadaver dissection. Testing established that significant improvement occurred in the students' ability to identify anatomic structures on diagnostic images. PMID- 2332317 TI - Cases from A3CR2. Young female with knee pain. Tuberculous arthritis. PMID- 2332318 TI - Cases from A3CR2. Ten-year-old boy with a limp. Sequelae of meningococcal sepsis. PMID- 2332319 TI - University radiology. A personal view. PMID- 2332320 TI - Future diagnostic radiology manpower needs. PMID- 2332321 TI - Structured approach in PLC (programmable logic controller) programming for water/wastewater applications. AB - This paper describes a methodology for efficient implementation of PLC programming for water/wastewater applications. The PLC was interfaced with a supervisory host computer which used touch screen equipped color monitors as operator interfaces. PLC ladder logic had to be designed to process real-world hardwired I/O as well as the I/O received from the host computer and/or touch screens, via a communications link. Standard "templates" of PLC networks were developed for (a) pump controls including provision for touch screen I/O; (b) PID control; (c) alarms; (d) motor run times; (e) square root extraction; (f) signal conversion, and (g) flow totalization. All logic was implemented using the standard templates. This structured approach led to efficient implementation, easy debugging/start-up, and easy to read uniform ladder logic. PMID- 2332322 TI - Lymphocyte activating factor activity in the serum and cerebrospinal fluid of patients with multiple sclerosis. AB - Serum and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS), patients with other (non-inflammatory) neurological diseases (OND), patients with non-inflammatory non-neurological diseases, and normal controls were assayed for lymphocyte activating factor (LAF) activity by thymocyte costimulation. LAF activity was detected in normal control sera, which did not differ significantly in this respect from MS or OND patient sera. Not were there significant differences by stage of MS (chronic progressive MS, MS in relapse and MS in remission) or between MS patients and the non-inflammatory non-neurological controls. Almost all the CFSs assayed presented lower values than did the corresponding sera. Serum and CSF after fractionation showed no significant increase in LAF activity except in the 2 MS patients in remission. From these data it may be assumed that LAF activity does not necessarily correspond to the clinical phase of MS. The possible role of LAF activity as a marker of MS progression has yet to be determined. PMID- 2332323 TI - Circulating thyroid and gastric parietal cell autoantibodies in patients with multiple sclerosis. AB - Multiple sclerosis (MS) is associated with complex abnormalities of immunoregulation and a role of autoimmunity in its pathogenesis has been accepted. MS is reportedly associated with several autoimmune diseases, but few studies are available on the prevalence of organ-specific autoantibodies in this condition. The aim of this study was to assess the frequency of anti thyroglobulin (TgAb), anti-thyroid microsomal (MAb) and gastric parietal cell (PCA) antibodies in 113 patients (63 females, 50 males, age ranging 15-62 years) with MS and in 51 neurological controls. The diagnosis of MS was made according to McDonald and Halliday criteria. TgAb and/or MAb were detected by passive hemagglutination in 19 (16.8%) patients with MS and in 3 (5.9%) of the controls. All positive TgAb and/or MAb were observed in MS females (19/63 = 30.1%), with significantly higher frequency than in female controls (X2 = 5.15, p less than 0.025). The presence of circulating thyroid antibodies was higher in patients with clinically definite or progressive probable MS and in those with long standing disease. In contrast with thyroid antibodies, no difference in the frequency of PCA, as assessed by radioimmunoassay, was observed between MS and controls. These data support a specific association between thyroid autoimmunity and MS. The appearance of thyroid autoimmune phenomena seems to be related to the reliability of the diagnosis of MS and the duration of the disease. PMID- 2332324 TI - Effects of selenium and vitamin E on muscular strength and blood parameters in Steinert disease. AB - Six patients with Steinert disease were treated with selenium and vitamin E, for a 24 month period, including a first phase of 12 months, 6 months wash-out interval and a second treatment phase of 6 months. Mean segmental strength values showed significant improvement during the first 12 months of therapy, while marked reductions of serum enzymes CPK, SGOT, SGPT and gamma-GT were observed in some patients. The results support the hypothesis that selenium may play a role in the development of muscle damage in Steinert disease. PMID- 2332325 TI - Scinticisternography in presenile and senile degenerative disease. AB - 86 patients suffering from various senile and presenile degenerative diseases were studied using scinticisternography with In111-DTPA. Flow reversal and delayed clearance were observed in 62 of these patients. These alterations, possibly related to the cerebrospinal fluid dynamics, show the aspecificity of the SC picture. The SC picture does not seem to be correlated to the clinical signs. PMID- 2332326 TI - A case of "crossed aphasia" in which the integrity of the left hemisphere is assessed by MRI. AB - We describe a 65-year-old right-handed (on the Edinburgh Inventory Test) woman who developed left hemiplegia and language disturbances after right hemisphere lesion. She showed global aphasia and left spatial neglect. To our knowledge, this is the first case of so called "crossed aphasia" in which the integrity of the left hemisphere is assessed by Magnetic Resonance Imaging (MRI). The association of aphasia and neglect is briefly discussed. PMID- 2332327 TI - Stroke due to paradoxical embolism. AB - We present a case of stroke in a young girl, preceded by a deep vein thrombosis and pulmonary embolism, both clinically asymptomatic, and accompanied by upper limb acute ischemia. Diagnosis of paradoxical embolism through a patent foramen ovale was made on clinical grounds and with contrast echocardiography. We discuss the main points leading to diagnosis, stressing the importance of contrast echocardiography. We also suggest that paradoxical embolism could be a more frequent cause of stroke than usually suspected. PMID- 2332328 TI - Post-traumatic extrapyramidal syndrome: case report. AB - We report the case of a young man with possible post-traumatic extrapyramidal syndrome. Some features of this case have a bearing on the controversy surrounding the existence of post-traumatic Parkinson disease. PMID- 2332329 TI - Hematoma of the inferior colliculus: uncommon cause of trochlear nerve deficit and contralateral sensory hemisyndrome. AB - A 57 year old man consulted us for sudden onset of acuphenes in the right ear, followed by diplopia on forward and downward gaze and paresthesias on the right side of the body. Examination of ocular movements revealed a deficit of the superior oblique muscle of the left eye. CT and MR brainscans imaged a punctate bleed of the left inferior colliculus. The patient was discharged after 16 days still complaining of diplopia on forward and downward gaze. There was no change in neurological status at follow-up. It is rare for an intracerebral hematoma to be located in the midbrain. The case we report is distinguished by the smallness of the lesion and the uncommon neurological deficit it caused. PMID- 2332330 TI - Side effects of low-dose cyclosporin A in the treatment of multiple sclerosis. PMID- 2332331 TI - Headache after lumbar puncture: failure of different preventive measures. PMID- 2332332 TI - Plasmapheresis with exchange as primary treatment for thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever and renal and neurologic dysfunction. As a result of the availability of plasmapheresis, we can report the results of 5 patients treated with plasmapheresis and exchange transfusion who also received intravenous corticosteroids as adjunctive therapy. Our 5 patients had a mean age of 41 years, and presented with a mean platelet count of 39 x 10(9)/L. Four of the 5 patients responded to treatment and were discharged in excellent condition. The 5th patient succumbed to her disease. We concluded that plasmapheresis with exchange transfusion is a rapid and effective therapy for TTP. PMID- 2332333 TI - Epidemiology of ocean sports-related injuries in Hawaii: 'Akahele O Ke Kai'. AB - Before attempting to prevent ocean activity injuries, as well as to improve treatment strategies, more information is needed regarding the numbers of injuries that are geographic and activity specific and the identification of persons at risk for such injury. Data on 276 injuries that occurred during ocean sports activities on the islands of Oahu and Hawaii over a 10-month period are presented. The injuries were mainly related to swimming and board-surfing, although serious injuries were found for almost all types of sports activities. The majority of those injured were young adult men who were local residents. Over 10% of the injuries required hospitalization, including 4 fatalities due to drowning and 5 spinal cord injuries due to trauma or to SCUBA-related, decompression incidents. Our study identifies the need for determining an estimate of the number of persons engaging in ocean sports, establishes the need for a single reporting system for injuries, determines potential risk factors, and suggests targets for prevention. PMID- 2332334 TI - PEP: peer education in health for student empowerment. AB - In an effort to assist teens to make healthier decisions and to support the Department of Education's health education program, the Departments of Health (DOH) and Education (DOE) have formed a partnership to design and implement a Peer Education Program (PEP). The initial funding for the program was provided through that partnership and the AIDS Omnibus bill. PMID- 2332335 TI - The epidemiology of radial head subluxation ('pulled elbow') in the Aberdeen city area. AB - The incidence of Radial Head Subluxation in young children in the Aberdeen City Area was ascertained by retrospective review to be 1.2% per year. One hundred and sixty-two cases were recorded, in children aged between 5 and 66 months. The epidemiological features of the condition are reviewed. Extrapolation of these figures to the population of England, Scotland and Wales would suggest an annual incidence of 50,000 cases. This is a condition treatable in general practice, provided of course that the patient is not taken direct to an Accident and Emergency Department. PMID- 2332336 TI - Edinburgh's community drug problem service--a pilot evaluation of methadone substitution. AB - The intravenous drug abusers of Edinburgh are known to have a high prevalence of infection with the Human Immunodeficiency Virus (HIV). A new service for the treatment of drug abusers in Edinburgh was commenced in April 1988. In this service, oral methadone substitution is frequently used to try to reduce the level of behaviour known to increase the risk of transmission of HIV. A questionnaire-based pilot study of the outcomes of oral methadone substitution therapy in 24 clients is described. The results indicate that the therapy is acceptable and may have a significant effect in reducing risk behaviour. PMID- 2332337 TI - Dental knowledge, beliefs, attitudes and behaviour of the Asian community in Glasgow. AB - Epidemiological studies suggest that Asians living in Britain, particularly children, have poor oral health. This study of the dental health knowledge, beliefs, attitudes and behaviour of a random sample of sixty-nine Asian adults in Glasgow aimed to identify some possible underlying factors. The dental health knowledge of Asians living in Glasgow appeared to be limited, specifically with regard to methods of reducing the incidence of caries. Thirty per cent could not name any foods which were known to be detrimental to dental health and only 30% felt that children under the age of five required access to dental services. The aesthetic value of a healthy mouth was highly appreciated by the majority of respondents and poor oral health was considered to be socially unacceptable. The Asian population examined would seem to be an appropriate target group for dental health education, since low knowledge levels rather than negative attitudes appear to cause Asians to be at high risk from caries. PMID- 2332338 TI - Dissemination of research findings: who wants what? AB - There is growing concern to ensure that the results of health services research reach, and are understood by, those who plan and provide health services. Because of the complexity and variability of services, it is often difficult to translate findings from one setting to another. This paper discusses an attempt to disseminate the findings of one study, Patterns and Pathways of Care of Old People, by visiting local health services on request. The main conclusion is that, for a qualitative study such as this, considerable effort is needed to predetermine which relevant research aspects and local people to bring together to make the exercise useful to either party. If dissemination of National Health Service (NHS) funded research is to be promoted, a central issue to be addressed is who is responsible for initiating and funding this stage. The paper raises a number of options. PMID- 2332339 TI - Greenwich. In the shadow of Kimberley. PMID- 2332340 TI - NHS and community care bill. Asset stripping threat to hospitals. PMID- 2332341 TI - Nuclear accidents: how people react. PMID- 2332343 TI - Training in the enterprise culture. PMID- 2332342 TI - Establishing a child health clinic in a deprived area. PMID- 2332344 TI - GPs ask for patients' views. PMID- 2332345 TI - The current status of dental health education. PMID- 2332346 TI - Promoting health at the swimming pool. PMID- 2332347 TI - Lease cars. Caught in the mileage trap. PMID- 2332348 TI - Greening health visiting. PMID- 2332349 TI - Immunohistochemical localization of Met5-enkephalin-Arg6-Gly7-Leu8 in the female genital organs and in the paracervical ganglion of the pig. AB - Indirect immunofluorescence method was used to study the localization and distribution of the proenkephalin A-derived octapeptide, Met5-enkephalin-Arg6 Gly7-Leu8 (MEAGL), in the paracervical ganglion and in the female genital organs of the pig. In the paracervical ganglion, a subpopulation of principal neurons and nerve fibers contained MEAGL immunoreactivity. In the vagina, numerous MEAGL immunoreactive nerve fibers were localized in the muscular membrane, under the serous membrane and in the submucous layer. The uterine cervix contained a great number of immunoreactive nerve fibers in muscular membrane and in submucous and subserous layers. The pattern of distribution of MEAGL-immunoreactive nerve fibers in the uterine horns was similar to that of cervix, but their number in the uterine horns was lower. MEAGL-immunoreactive fibers were also observed through different oviductal layers. In the ovary a low number of immunoreactive fibers were seen in the medullary and cortical parts of the organ. The results of this study indicate that the female genital organs, particularly the uterus and vagina, of the pig receive dense innervation by nerve fibers containing the proenkephalin A-derived octapeptide MEAGL. The presence of MEAGL in principal neurons and fibers of the paracervical ganglion suggests that a large proportion of them originate from neurons of the paracervical ganglion. PMID- 2332350 TI - Boar sperm membranes antigens. II. Reorganization of an integral membrane antigen during capacitation and acrosome reaction. AB - The dynamics of the cell surface during the process of capacitation is impressively shown by means of a monoclonal antibody directed against the P86/5 antigen. This glycoprotein was located in the sperm plasma membrane using the colloidal gold method in combination with specimen preparation in toto. The antigen is absent at the rostral tip of non-capacitated spermatozoa, but forms clusters over the principal segment and the equatorial segment after induction of capacitation. This formation of microdomains with different properties may be a prerequisite for the onset of the acrosome reaction (AR). During AR the diffusion barrier for the P86/5 antigen breakes down and the antigen occupies now the rostral crescent-like area of the sperm head. These observations are discussed with respect to zona binding and induction of the AR in boar spermatozoa. PMID- 2332351 TI - Microphotometric determination of enzymes in brain sections. II. GABA transaminase. AB - The tetrazolium salt procedure of van Gelder (1965) for the demonstration of GABA transaminase (GABAT; the most important GABA degrading enzyme) was adapted for microphotometric measurements of GABAT activities in brain sections using the hippocampus of rats as selected brain region. The final incubation medium consisted of 50 mM GABA, 5 mM alpha-ketoglutarate, 7 mM NAD, 10 mM sodium azide, 6 mM nitroblue tetrazolium chloride, 20 mM malonate and 15% polyvinyl alcohol in 0.05 M Hepes buffer; the final pH was 8.0. There was a linear relationship between GABAT activity and section thickness up to 14 microns and between GABAT activity and reaction time at least up to 20 min (kinetic and end-point measurements). Phenazine methosulfate as an exogenous electron carrier and pyridoxal-5-phosphate as coenzyme of GABAT did not enhance the demonstrable GABAT activities, whereas sodium azide as a blocker of the respiratory chain resulted in an increase of demonstrable enzyme activities. A coreaction of succinate dehydrogenase was excluded by the use of malonate (competitive inhibitor). Using the incubation medium described GABAT activities were demonstrated via the endogenous enzymes succinic semialdehyde dehydrogenase and NADH tetrazolium reductase which were shown to be not rate limiting and seems to be similarly localized as GABAT. PMID- 2332352 TI - N-terminal amino acid sequence, immunohistochemical localization and tissue distribution of a plasma membrane protein (Prot17) of rat enterocytes. AB - Prot17, a protein of the basolateral membrane of rat small intestine with a mol.wt. of 17 kDa, can be isolated using a previously described method (Schiechl 1988). It occurs in the membrane as an oligomer with a mol.wt. of 90 kDa. In the present study a polyclonal antibody specific for Prot17 was used to explore by immunohistochemical techniques the tissue distribution of Prot17 and its ultrastructural localization within the cells. Furthermore the amino acid sequence of the N-terminal part of this molecule up to position 17 could be analyzed. The results are summarized as follows: Prot17 is a membrane anchored protein. Its partial amino acid sequence suggests that it is neither identical nor related to other known proteins. Immunofluorescence studies revealed, that it occurs only in epithelial cells. It is mainly found in the absorptive and goblet cells of the intestine and the acinar cells of the pancreas. Smaller quantities are found also in the bile duct epithelium of the liver, in the proximal tubule cells of the kidney and in the cells of the respiratory epithelium. Ultrastructural localization of Prot17 was possible in the intestinal epithelium and pancreas acinar cells. In both cell types it was found in the basolateral and microvillous membrane. In pancreas, Prot17 was also detected in the membrane of the zymogen granules. In the absorptive cells of the intestine Prot17 was found in both the membrane and the contents of subluminal vesicles. Furthermore, in apical granules of secretory cells of the respiratory epithelium binding of Prot17 specific antibody was found in the granular content, the membrane being negative. PMID- 2332353 TI - Microphotometric determination of enzymes in brain sections. III. Glutamate dehydrogenase. AB - An incubation medium was established for the microphotometric demonstration of glutamate dehydrogenase (Gldh) in cryostat sections of the rat hippocampus which served as an exemplary brain region. The final incubation medium consisted of 100 mM L-glutamic acid monosodium salt, 5 mM NAD, 10 mM sodium azide (NaN3), 5 mM ADP, 20 mM sodium chloride, 0.15 mM phenazine methosulfate (PMS), 5 mM nitroblue tetrazolium chloride and 22% polyvinyl alcohol (PVA) in 0.05 M Hepes buffer; the final pH was 7.5. The study showed that in the histochemical demonstration of Gldh the use of relatively high PVA concentrations were necessary to avoid diffusion artefacts because Gldh seems to be only loosely bound to the mitochondrial matrix. The use of NaN3 as a blocker of the respiratory chain was indispensible, because without NaN3 most reduction equivalents were lost through the respiratory chain. With PMS as an exogenous electron carrier, the demonstrable Gldh activities increased significantly indicating that, in the case of Gldh, the endogenous NADH tetrazolium reductase was not sufficiently effective. Furthermore, it was shown that Gldh was affected by many small molecules (e.g. activation by sodium ions, inhibition by magnesium and calcium ions) so that minor variations of the incubation conditions may cause major differences in demonstrable activities. PMID- 2332354 TI - Formula for selecting quality in-office lab equipment. PMID- 2332355 TI - Another hurrah for a 'smoke-free' environment. PMID- 2332356 TI - Laser surgery for the treatment of squamous cell carcinoma of the penis. AB - We describe our experience with six cases of squamous cell carcinoma of the penis treated with the carbon dioxide and neodymium yttrium aluminum garnet (Nd:YAG) lasers. One patient had carcinoma in situ. One patient had a T1 tumor. Two patients had T2 disease and two patients had T3 carcinoma of the penis when seen. The patients were followed up from 13 to 64 months. The patients with carcinoma in situ and T1 carcinoma of the penis were tumor-free at a mean follow-up of 45 months. One patient with T2 carcinoma apparently had a complete response to surgery; however, he was seen 56 months after the initial laser treatment with a new invasive penile tumor located at a different site that failed to respond to laser treatment and required a penectomy. Another man with T2 carcinoma as well as the two men with T3 carcinoma failed to respond to laser treatment and required a penectomy. It appears that laser surgery offers the potential for cure in patients with carcinoma of the penis with superficial involvement. PMID- 2332357 TI - The pull toward the vacuum: osteopathic medical education in the 1980s. AB - During the 1980s, the two major influences in osteopathic medical education were the increasingly large number of new DOs seeking internships and residencies and the loss of training sites as a result of the shrinking osteopathic hospital network. Owing mainly to a declining interest in primary care by young MDs, allopathic postdoctoral program directors, particularly in primary care specialties, began to actively recruit osteopathic physicians. An oversupply of positions on the allopathic postdoctoral side and an undersupply of residency positions in osteopathic postdoctoral programs contributed to a crossover trend. The programs approved by the Accreditation Council for Graduate Medical Education have made significant inroads in attracting DOs. It has reached the point where two out of every three DOs currently training in a primary care residency can be found in an allopathic program. If it continues, this pattern will have a significant impact on the character of osteopathic medical education. PMID- 2332358 TI - Proposed legislation on use of animals in Pennsylvania. PMID- 2332359 TI - Abbreviations and other shortcuts in communication. PMID- 2332360 TI - Excision of melanomas in horses. PMID- 2332361 TI - Out and about. Spaceflight scratched by a heartbeat. PMID- 2332362 TI - Hazard analysis and critical care point system could help standardize food safety. PMID- 2332363 TI - Anisakiasis becoming problem in United States. PMID- 2332364 TI - FSIS study exonerates milo feed as contaminant. PMID- 2332366 TI - Animals and the health of the nation. PMID- 2332365 TI - Difficult dermatologic diagnosis. PMID- 2332367 TI - Verbal cruelty to clients. PMID- 2332368 TI - Back to school again: first step toward a new career. PMID- 2332369 TI - Eperythrozoon wenyonii infection in dairy cattle. AB - Approximately 10 of 100 young heifers that had recently delivered their first calf--members of a large Colorado dairy herd--had a syndrome of swollen teats and distal portions of the hind limbs, prefemoral lymphadenopathy, transient fever, rough coat, decreased milk production, and subsequent weight loss and reproductive inefficiency. Acute clinical signs of disease were associated with large numbers of Eperythrozoon wenyonii seen on blood smears, and resolution of signs correlated with reduction or disappearance of the parasite. Other known causes of peripheral edema could not be documented. The parasite was transmitted to 4 of 7 nonlactating dairy cows destined to be culled and a splenectomized calf via IV inoculation of blood from parasitemic heifers, but clinical signs of infection were not induced. PMID- 2332370 TI - Use of an enzyme-linked immunosorbent assay to estimate prevalence of paratuberculosis in cattle of Florida. AB - A survey was conducted from 1986 through 1987, for which an ELISA was used to obtain information on the prevalence of Mycobacterium paratuberculosis infection in cattle of Florida. Results revealed prevalence of 8.6% in beef cattle and 17.1% in dairy cattle. In beef and dairy cattle, prevalence increased with increasing herd size. It was concluded that ELISA-detectable circulating antibodies to M paratuberculosis are widespread in cattle of Florida. PMID- 2332371 TI - Serologic survey for Borrelia burgdorferi antibody in horses referred to a mid Atlantic veterinary teaching hospital. AB - Blood samples obtained from 13 of 100 (13%) and 6 of 91 (7%) horses at the George D. Widener Hospital for Large Animals in the months of June and October, respectively, had antibody to Borrelia burgdorferi as determined by ELISA. Horses from the states of New York, Maryland, Delaware, New Jersey, and Pennsylvania were seropositive for B burgdorferi. The frequency of antibody response in horses from New Jersey was greater (P less than 0.05) than the frequency of antibody response in horses from Pennsylvania or that of horses from the other states combined. Statistically significant difference was not found when a comparison was made between horses with serotiter and open diagnosis of neurologic or musculoskeletal disease and horses with negative serotest results and open diagnosis of neurologic or musculoskeletal disease. PMID- 2332372 TI - Decreased erythrocyte potassium concentration associated with exercise-related myopathy in horses. AB - To investigate the possibility that a disorder of potassium balance may have a role in the development of equine rhabdomyolysis, the potassium concentration within erythrocytes (RBC [K+]) and plasma (P [K+]) was measured in 3 groups of horses: group 1, eight 2-year-old fillies that had postexercise muscle soreness within 48 hours of sample collection; group 2, ten 2-year-old fillies subjected to identical management and training conditions (as fillies of group 1) and that did not have signs of myopathy; and group 3, 32 yearlings of both sexes on the farm of origin of groups 1 and 2 that were pastured and not in training. Creatine kinase activity in serum from horses of groups 1 and 2 was also measured. The mean P [K+] was not significantly different between groups, whereas the mean RBC [K+] was significantly (P less than 0.01) lower in group-1 fillies vs group-2 fillies and group-3 horses. Group-1 fillies also had markedly high serum creatine kinase activity. Results of the study revealed significantly lower RBC [K+] in horses that had had signs of myopathy within the preceding 48 hours. This does not prove a causal relationship between RBC potassium depletion and myopathy, but does suggest that decreased RBC [K+] may be observed in horses with exercise related myopathy. PMID- 2332373 TI - Measurement of conchal atrophy and pneumonic lesions and their association with growth rate in commingled feeder pigs. AB - A group of 85 commingled feeder pigs was fed on a totally confined feeding floor until slaughter. Mean daily weight gain was calculated for each pig. At slaughter, the nose of each pig was cross-sectioned and scored for conchal atrophy by use of 2 methods. One method ascribed a score based on a linear measurement of the distance between the ventral scroll of the ventral conchae and the ventral floor of the nasal cavity. The other method ascribed a score based on a subjective evaluation of the degree of conchal degeneration according to previously published guidelines. The amount of pulmonary consolidation attributable to pneumonia was also estimated for each pig. Association was not found between growth rate and conchal atrophy, as determined by linear measurement scores. A negative correlation existed between growth rate and conchal atrophy, as determined by subjective evaluation scores. Pigs with extensive pneumonic lesions (consolidation of 20 to 30% of total lung volume) grew slower than pigs with milder pneumonic lesions. Results of this study indicate that subjective evaluation scores of conchal atrophy may be more useful in predicting growth rate than are linear measurement scores. PMID- 2332374 TI - Peritracheal abscess associated with tracheal collapse and bilateral laryngeal paralysis in a dog. AB - Tracheal collapse and bilateral laryngeal paralysis were diagnosed in an 8-month old Cocker Spaniel that had acute onset of dyspnea and cyanosis. Surgical exploration of the mediastinum revealed an abscess involving the ventral wall of the trachea immediately caudal to the thoracic inlet. Both recurrent laryngeal nerves were entrapped in fibrous tissue surrounding the abscess. The dog recovered after tracheal resection and anastomosis and freeing of the entrapped nerves. The peritracheal abscess was suspected to have been the result of esophageal perforation secondary to foreign body penetration. PMID- 2332375 TI - Clinical remission following plasmapheresis and corticosteroid treatment in a dog with acquired myasthenia gravis. AB - A 7-year-old sexually intact male Labrador Retriever with regurgitation and generalized muscular weakness resulting from acquired myasthenia gravis received 2 plasmapheresis treatments in combination with corticosteroid treatment. Plasmapheresis was performed in an attempt to rapidly lower serum acetylcholine receptor binding antibody (AChR Ab) concentration. Seven days after the second plasmapheresis treatment, the dog's muscular strength was normal, which coincided with a 70% decrease in serum AChR Ab concentration. Because the dog also received corticosteroids, it is impossible to determine how much of the clinical improvement resulted from plasmapheresis. PMID- 2332376 TI - Suspected familial renal disease in chow chows. AB - Renal disease was diagnosed in 6 young Chow Chows. Clinical abnormalities included vomiting, polyuria, polydipsia, and weight loss. Common abnormal laboratory findings were azotemia, hyperphosphatemia, hypocalcemia, nonregenerative anemia, and low urine specific gravity. All 6 dogs had similar microscopic renal lesions. characterized by interstitial fibrosis, a population of small glomeruli, and lack of inflammatory cells. A familial basis for the renal disease is suggested because of its development in 4 closely related dogs. PMID- 2332377 TI - Primary hypoparathyroidism in a cat. AB - Primary hypoparathyroidism caused by lymphocytic parathyroiditis was diagnosed in a cat. Other causes of hypocalcemia (ethylene glycol toxicosis, phosphate enema administration, pancreatitis, renal insufficiency, and malabsorption) were ruled out on the basis of history, clinicopathologic data, and lack of supportive clinical signs, which in this cat included inappetence and tetanic muscle spasms. The diagnosis was confirmed by histologic examination of a surgically excised thyroparathyroid lobe that comprised lack of recognizable parathyroid tissue and a lymphocytic plasmacytic infiltrate adjacent to the cranial pole. A treatment regimen similar to that for iatrogenic postthyroidectomy hypoparathyroidism was successful in controlling clinical signs of the disease. PMID- 2332378 TI - Acquired myasthenia gravis in a cat with thymoma. AB - A 4-year-old castrated Abyssinian cat was evaluated for profound neuromuscular weakness. Results of electromyography and repetitive nerve stimulation tests were normal. Thoracic radiography revealed a cranial mediastinal mass, which was excised and identified as a thymoma. Serum acetylcholine receptor antibodies were detected at high concentration, supporting a diagnosis of acquired myasthenia gravis. Clinical signs of disease responded to treatment with pyridostigmine and corticosteroids. PMID- 2332379 TI - Caudal vena caval thrombosis in a cow. AB - Caudal vena caval thrombosis was diagnosed in a 13-year-old Santa Gertrudis cow with a history of chronic weight loss. Anemia, abnormal lung sounds, hemoptysis, and melena were the predominant clinical signs of vena caval thrombosis. PMID- 2332380 TI - What is your diagnosis? Fracture of the dorsomedial surface of the medial trochlear ridge of the talus. PMID- 2332381 TI - Effect of exogenous porcine somatotropin administration on nitrogen and energy metabolism in three genotypes of pigs. AB - Effects of exogenous administration of porcine recombinant somatotropin (rpST) on protein gain and metabolic rate were measured in three genotypes (castrated males) of pigs (Pietrain, Duroc and a crossbreed between Dutch Yorkshire and Dutch Landrace). Six pigs of each genotype were assigned at approximately 60 kg to receive pST doses of either 0 (C) or 14 mg (T) administered i.m. twice weekly over 10 wk. Pigs were housed in individual metabolism cages at a room temperature of 20 to 22 degrees C and received feed at 2.6 times maintenance. Protein gain (N x 6.25) was measured over the final 6 wk of the 10-wk test period. For 2 wk in the test period (wk 2 and wk 5), six pigs of each treatment x genotype group were placed in a large respiration chamber and energy balances (in protein and fat) and metabolic rate were measured. Rate of weight gain measured over the final 6 wk of the experimental period increased by 105 g/d (13%) with rpST administration (P less than .01). Daily protein gain over 6 wk was increased by 48 g/animal with application of rpST (P less than .001). There was a genotype x treatment interaction (P less than .01) for protein gain. Daily protein gain in Durocs with pST treatment was increased (39%) more than in crossbreds (31%). Daily fat gain was decreased by 42 g/animal (P less than .001) by T. Daily heat production with rpST was increased by 12 kcal/kg.75, which is comparable to a 12% increase in the maintenance energy requirement. PMID- 2332382 TI - Intramuscular collagen and serum hydroxyproline as related to implanted testosterone, dihydrotestosterone and estradiol-17 beta in growing wethers. AB - Relationships of implanted testosterone, dihydrotestosterone and estradiol-17 beta to collagen degradation and intramuscular collagen concentration and stability were determined. Intramuscular collagen content, solubility and shrinkage temperature and serum hydroxyproline were analyzed in groups of six rams, wethers, and wethers implanted with various levels of testosterone or dihydrotestosterone and groups of 10 rams, wethers and wethers implanted with estradiol-17 beta, dihydrotestosterone or a combination of these two steroids. Intramuscular collagen content in both experiments was higher (P less than .05) in muscles of rams than in muscles of wethers. Administration of the highest level of testosterone to wethers raised (P less than .05) total and insoluble intramuscular collagen to concentrations noted in rams. Administration of the testosterone metabolite, dihydrotestosterone, to wethers had no effect on intramuscular collagen. Administration of estradiol-17 beta to wethers tended to raise concentrations of intramuscular collagen so that they were no longer lower (P less than .05) than those in rams. Collagen stability as measured by solubility and thermal shrinkage temperature did not differ among rams, wethers or implanted wethers (P greater than .05). Increases in collagen accretion due to hormone administration were observed to be the result of increases in the insoluble portion of the intramuscular collagen (P less than .05). PMID- 2332383 TI - Physiological relationships between microbiological status and dietary copper levels in the pig. AB - Ten germ-free pigs and 10 conventionally reared pigs were fed one of two nutritionally balanced diets containing either 16 ppm Cu (basal) or 283 ppm Cu (high-Cu) to evaluate the physiological relationships between Cu and microbiological environment. Germ-free pigs tended to have higher ADG and average daily feed intake (ADFI) than conventionally reared pigs. Feeding the high-Cu diet tended to reduce ADG and ADFI in germ-free pigs but it increased ADG and ADFI in conventionally reared pigs. Hemoglobin and hematocrit were higher in germ free pigs than in conventionally reared pigs (P less than .001), and hematocrit (P less than .01) and erythrocyte count (P less than .06) were reduced by feeding the high-Cu diet. Germ-free pigs had lower total leukocyte count (P less than .01) and the relative percentages of differentiated leukocytes were altered compared with conventionally reared pigs. Feeding the high-Cu diet increased the percentage of band neutrophils and monocytes in germ-free pigs but reduced the percentage of these cells in conventionally reared pigs (P less than .04). Germ free pigs had higher concentrations of Cu and Zn in liver and plasma (P less than .001) and greater plasma ceruloplasmin oxidase activity (P less than .001) than conventionally reared pigs did. The high-Cu diet increased liver Cu and Zn (P less than .001) and plasma Cu (P less than .001) and reduced liver and plasma Fe (P less than .05). Organ weights (g/kg BW) differed between germ-free and conventionally reared pigs, and feeding the high-Cu diet reduced thymus weights (P less than .002). Intestinal weight and thickness were reduced in germ-free pigs, and feeding the high-Cu diet generally reduced villus height and width and crypt depth in germ-free pigs, whereas it increased these measurements in conventionally reared pigs. PMID- 2332384 TI - The effects of selected bulky substituents on the pulmonary toxicity of 3-furyl ketones in mice. AB - Preliminary studies examined the toxicity of a series of simple alkyl 3-furyl ketone congeners of perilla ketone, 1-(3-furyl)-4-methylpentan-1-one (1), in mice, but little was known about how aromatic or bulky side chains might affect toxicity. Therefore, 3-furylphenyl ketone (2) 3-furylphenethyl ketone (3) and 1-3 furyl-4, 4-dimethylpentan-1-one (4) were synthesized to examine this problem. The 48-h LD50 (i.p.) in Notre Dame Swiss mice for each analog was greater than that of the parent toxicant, perilla ketone (1, 30 +/- 5; 2, 173 +/- 4; 3, 150 +/- 11; 4, 79 +/- 5 mumol/kg). Absorption and distribution of these compounds should be similar based on their lipophilicities. Preliminary evidence suggested that the reduced toxicities of 2, 3 and 4 compared with 1 cannot be explained on the basis of 13C-NMR (electron density) characteristics. Instead, the reduced potency likely is the result of steric hindrance of bioactivation by the bulky side chain substituents and(or) alternative metabolism on the phenyl ring rather than the furan ring of 2 and 3. PMID- 2332385 TI - Effects of the ionophore tetronasin on nitrogen metabolism by ruminal microorganisms in vitro. AB - The effects of tetronasin on ruminal protein metabolism were investigated in vitro using ruminal fluid from cattle receiving tetronasin in the diet, ovine ruminal fluid from animals not receiving tetronasin and pure cultures of proteolytic ruminal bacteria. Ruminal fluid from cattle receiving tetronasin in a predominantly barley diet had lower proteolytic (76% of control, P less than .10) and deaminative (58% of control, P less than .05) activities than controls after 42 d. The effect of deamination disappeared after 84 d, although the proteolytic activity remained lower (P less than .10) than that of controls. When tetronasin was added in vitro to ruminal fluid from sheep not receiving the ionophore, proteolytic activity (14C-labeled casein hydrolysis) was unaffected, but the rate of ammonia production from amino acids was decreased by 87% (P less than .01). Oligopeptide breakdown was inhibited to a lesser extent (21%, P less than .05). Dipeptidase activity (dialanine hydrolysis) was not affected. The addition of tetronasin to cultures of the ruminal bacteria Ruminobacter amylophilus and Bacteroides ruminicola had no influence on their protease, deaminase or dipeptidase activities. However, when the bacteria were adapted to grow in the presence of tetronasin, deamination of amino acids was severely inhibited (87 to 100%, P less than .01), even when tetronasin was absent from the incubation mixture. Tetronasin had no effect on the proteolytic activity of adapted cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332386 TI - Ruminal fermentation pattern, bacterial population and ruminal degradation of feed ingredients as influenced by ruminal ammonia concentration. AB - The effects of ruminal ammonia concentration on bacterial numbers, fermentation pattern and degradation of feed ingredients in the rumen were examined with three nonlactating Holstein cows fitted with ruminal cannulas. Cows were fed twice daily a complete mixed diet (90% whole plant oat silage and 10% concentrate mixture) containing 11.1% CP on a DM basis. Ammonium bicarbonate (NH4HCO3) was infused continuously into the rumen at levels of 0, 95, 190 or 280 g/d. Infusion of NH4HCO3 linearly increased (P less than .05) the concentrations of ruminal ammonia and blood urea N. Total VFA concentrations and mixed bacterial numbers also were increased (P less than .05) by NH4HCO3 infusion. Infusions of NH4HCO3 increased (P less than .05) butyrate and decreased (P less than .05) isobutyrate and isovalerate proportions. Infusion of NH4HCO3 increased (P less than .05) rate of degradation of soybean meal DM but did not (P greater than .05) influence degradation characteristics of fish meal and barley grain. In conclusion, supplementation of N by continuous infusion of NH4HCO3 appeared to stimulate bacterial growth and fermentation but it did not influence extent of ruminal degradation of selected feed ingredients. PMID- 2332387 TI - Effects of dietary aluminum and phosphorus on magnesium metabolism in dairy calves. AB - The metabolism of Mg was studied in young dairy calves fed two levels of added Al (0 and .20% Al) and two levels of added P (0 and .22% P) for 7 wk. The four treatments were 1) normal P-low Al, 2) low P-low Al, 3) normal P-high Al and 4) low P-high Al. The basal diet (low P-low Al) contained, by analysis, .132% P, .021% Al and .17% Mg. Added Al did not affect (P greater than .10) serum Mg. An Al x P interaction on bone Mg was detected (P less than .01). Magnesium was reduced in tibia shaft (.34 vs .44%) and in tibia joint (.43 vs .53%) in calves fed high Al in the presence of normal dietary P, but Mg was not reduced in the calves fed low-P diets. Apparent absorption of Mg was reduced by approximately five-fold (.18 g/d vs -.84 g/d, P less than .01); urinary Mg excretion was reduced 31% (1.12 g/d vs .77 g/d, P less than .01); and Mg retention declined 41% (-95 g/d vs -1.61 g/d, P less than .01) in calves fed added A1. Compared with calves fed low-P diets, calves fed normal levels of P had a higher Mg concentration in tibia shaft (P less than .01) and tibia joint (P less than .05). The data indicate that supplemental Al may adversely affect Mg metabolism in calves. PMID- 2332388 TI - Influence of grain and monensin supplementation on ruminal fermentation, intake, digesta kinetics and incidence and severity of frothy bloat in steers grazing winter wheat pastures. AB - Three 10-d collection periods (April 4 to 14, early April, EApr; April 23 to May 3, late April, LApr; May 10 to 20, 1984, mid-May, MMay) were conducted to evaluate effects of no supplement (C), .5 kg-head-1.d-1 (as-fed basis) supplemental grain (steam-flaked milo, G) or G plus 170 mg monensin.head-1.d-1 (M) on forage intake and digestion by 12 ruminally cannulated beef steers (four/treatment; avg initially BW = 393 kg) grazing irrigated winter wheat pasture. Ruminal pH was greater (P less than .01) for M than for C or G during EApr but was not altered by treatments in LApr or MMay. Compared with C, ruminal NH3 was decreased (P less than .10) by G and M (5 h after supplementation) in EApr, decreased (P less than .05) by G (2h) and increased (P less than .05) by M (8 h) in LApr and decreased (P less than .10) by G (-1h) in MMay. Treatments had little influence on total VFA concentrations or on molar proportions of acetate and propionate. Butyrate molar proportion was decreased (P less than .10) by M during EApr and LApr, but not during MMay. Monensin increased (P less than .05) fluid passage rate compared with C and G in EApr but not in other periods, Particulate passage measurements did not differ (P greater than .10) among treatments within periods. Forage DM intake was not influenced (P greater than .10) by supplementation during any period. Extent of in situ forage DM disappearance was greater (P less than .10) for M than for C or G during EApr (12 and 30 h of incubation) but was not different (P greater than .10) in LApr or MMay. Incidence of frothy bloat was decreased (P less than .05) by M during EApr; this reduction may have been related to effects of M on ruminal pH, forage digestion and fluid passage. PMID- 2332389 TI - Effect of sex and exogenous porcine somatotropin on longissimus muscle fiber characteristics of growing pigs. AB - Thirty-seven pigs with an initial live weight of 60 kg were used to investigate the effects of daily exogenous porcine somatotropin (pST) administration at two dose levels (0 and 100 micrograms.kg-1.d-1) for a 31-d period on muscle fiber characteristics and meat tenderness of boars, gilts and barrows. Excipient boars and gilts had more alpha W and fewer alpha R fibers than did those receiving pST. The percentage of muscle fiber type for barrows was not affected by pST treatment. The administration of pST resulted in an increase in muscle fiber size for all three fiber types in all three sexes, but these changes were of greater magnitude in barrows (31.8%) and gilts (27.8%) than in boars (9.3%). Somatotropin negated the intrinsic sex effect differences in fiber area of the pigs. There was no difference in tenderness among excipient boars, barrows and gilts; however, with the inclusion of pST, shear force decreased in boars and gilts and increased in barrows. A high proportion of the pST-treated pigs contained giant fibers in the longissimus muscle. Furthermore, a small proportion of the pST-treated pigs exhibited pale, soft, exudative muscle. Whether the giant fiber anomalies occurred through increased muscle activity or from fibers undergoing degenerative changes was not determined. PMID- 2332390 TI - Effects of nutrition, sex of calf and breed type on response to zeranol: preweaning growth. AB - An experiment was conducted to evaluate the effects of breed, sex and plane of nutrition on the growth response to zeranol in Angus and crossbred calves prior to weaning. Eighty-eight heifers and 118 steers received either a high or low plane of nutrition using a first and last grazing technique. Half of the calves in each nutrition group received a zeranol implant (36 mg) at an average age of 3.4 mo. Both zeranol and the higher level of nutrition increased (P less than .001) growth rate prior to weaning (7.4 mo of age). Zeranol did not affect hip height at weaning (P greater than .1), but calves on the higher plane of nutrition were taller (P less than .01) than calves on the lower plane of nutrition. The zeranol x nutrition interaction was not significant (P greater than .1) for growth rate or hip height. Steers grew faster (P less than .01) preweaning and were taller (P less than .01) at weaning than heifers. Crossbred calves gained more rapidly (P less than .001) preweaning and were taller (P less than .001) at weaning than Angus calves were. Neither sex nor breed interacted with zeranol to influence any of the traits examined. Based on these results we conclude that preweaning growth was affected by zeranol and this effect was consistent across sexes, breeds and planes of nutrition tested. PMID- 2332391 TI - Effects of melatonin and progesterone administered to ewes in spring and summer. AB - Melatonin (MEL) was evaluated for effects on LH, prolactin (PRL) and fertility in spring (Exp. 1, 2) and summer (Exp. 3 to 5). In Exp. 1, 17 ovariectomized ewes bearing estradiol implants were fed 3 mg MEL or vehicle for 44 d beginning May 1. Melatonin decreased (P less than .001) PRL levels but had no effect on LH secretion and response to GnRH. In Exp. 2, 12 ewes each received a 40-d MEL ear implant or a sham implant on March 31. Progesterone-releasing pessaries (CIDR) were applied for 12 d and were withdrawn concomitant with ram joining on May 7. Neither treatment stimulated follicular development or induced estrus or ovulation. Exp. 3 and 4 were contemporary 2 x 2 factorial trials with 24 ewes at each of two locations. Melatonin implants were administered on June 29 and CIDR on July 22. The CIDR were removed and rams (Exp. 3, vasectomized; Exp. 4, fertile) were joined on August 3. Days from introduction of rams to estrus were reduced (P less than .05) by CIDR but not by MEL. All ewes lambed in Exp. 4, and days to estrus and conception were reduced (P less than .001) by CIDR but not by MEL. Exp. 5 was designed like Exp. 4 except that MEL implants were inserted June 20 and rams were joined August 8. Intervals from introduction of rams to estrus were reduced (P less than .01) by both MEL and CIDR treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332392 TI - Bromocriptine-induced reduction of body fat in pigs. AB - An experiment was conducted with 36 crossbred finishing pigs (18 male castrates and 18 females) to evaluate the effect of bromocriptine implants on growth, feed intake, feed efficiency, plasma urea nitrogen (PUN) and carcass characteristics. Three levels of bromocriptine (0, 5 and 10 mg/[pig.d]) were administered, via implants at the base of the ear, to six (two replicates of three) male castrates or to six (two replicates of three) intact female pigs (2 x 3 factorial arrangement of treatments). Average initial weight of pigs at the time of implantation was 89.7 kg, and the implants remained in the pigs for 28 (replicate 1) or 30 (replicate 2) d prior to slaughter. Gain, feed intake and efficiency of feed utilization were not affected (P greater than .10) by bromocriptine. Plasma urea nitrogen was lower in female pigs administered 10 mg bromocriptine; bromocriptine did not affect PUN of male pigs (gender x bromocriptine, P less than .08). Tenth rib fat thickness and average backfat thickness were lower (P less than .06) and percentage of muscling was higher (P less than .06) in pigs implanted with bromocriptine. Female pigs had less 10th rib fat but larger loin eye areas and a greater percentage of muscling than male pigs. PMID- 2332393 TI - Techniques for estimation of milk yield in beef cows and relationships of milk yield to calf weight gain and postpartum reproduction. AB - Milk production is a primary factor controlling weaning weight of beef calves. The purpose of this experiment was to develop a practical and reliable on-farm method of estimating milk production and to relate estimates of milk production and milk composition to preweaning weight gain of calves. A second objective was to relate milk production to postpartum ovarian activity. Milk production of spring- and fall-calving grade Angus cows was estimated by machine milking (MM; average of 66, 123 and 189 d postpartum) and weigh-suckle-weigh (WSW; average of 50, 95, 136 and 179 d postpartum) techniques following overnight calf removal. Cows and calves were weighed monthly and the postpartum interval to first ovulation following calving was determined. The repeatability of the estimated milk production by MM (.97) was higher (P less than .01) than by WSW (.35). The correlation of average WSW and average MM estimates of milk production with preweaning calf gain were high and similar (greater than .75). Inclusion of milk composition did not improve the multiple correlation of MM-estimated milk production and calf gain. Neither milk production in early lactation (-.06) nor prebreeding weight change (-.07) was correlated with postpartum interval to ovulation. Machine milking was a repeatable method of estimating milk production of beef cows and can be used to evaluate effects of management variables on lactation of beef cows. PMID- 2332394 TI - Selection line x diet interactions for two lines of pigs fed 12 or 24% protein diets. AB - An experiment with crossbred swine was conducted over six generations of selection based on an index (Index) of average daily gain in weight (ADG) in a test period from 56 d of age to 91 kg gross weight and average backfat thickness (ABF) measured from ultrasonic scans at 91 kg. Test pigs of the high protein select (HS) and control (HC) lines were fed a 24% crude protein (CP) diet and pigs of the low protein select (LS) and control (LC) lines were fed a 12% CP diet during the test period. The extent of genetic (selection line) x environmental (dietary) interaction effects was determined based on feeding closely related boars and gilts from both the HS and LS lines on both diets. Tests were conducted in 1986 and 1987 with progeny of the fifth and sixth generations of selection. Records for 472 pigs sired by 37 boars and out of 101 dams were analyzed for effects of selection and diets on AGE of pig at 91 kg, ADG, ABF, LMA (longissimus muscle area at the last rib) and Index. Statistically significant interactions effects of line x diet were noted (P less than .01) for AGE, ADG and Index, traits with low to moderate heritabilities (h2). For ABF and LMA, body composition traits with moderate or higher h2, interaction effects of line x diet were near zero. These results suggest that for best all-around future performance, traits such as AGE and ADG, selection probably should be practiced under dietary conditions under which future populations will be produced. For body composition traits such as ABF and LMA, selection probably would be more effective if pigs were fed a more enriched protein diet. However, as a practical matter, to more rapidly improve the genetic merit of the swine population, both the central station and on-the-farm testing programs should be conducted under standard commercial production systems. PMID- 2332395 TI - Life-cycle evaluation of Bos taurus and Bos indicus X Bos taurus breed types in a dry, temperate climate: performance of mature dams. AB - Mature dams representing Hereford, Red Poll, F1 Hereford x Red Poll, F1 Red Poll x Hereford, F1 Angus x Hereford, F1 Angus x Charolais, F1 Brahman x Hereford and F1 Brahman x Angus breed types were evaluated. All cows were bred to Limousin sires to produce two-way or three-way-cross progeny. Mature Brahman x Hereford dams produced a higher (P less than .05) percentage of live calves than Herefords, but dam breed differences in percentage of calves weaned relative to the number of cows exposed for mating were not statistically significant. Progeny of Angus x Charolais and Red Poll dams were outstanding in weaning weight, but Hereford and Brahman-cross calves were below average. Planned comparisons showed that Angus x Charolais calves were heavier (P less than .01) at weaning than Hereford (23.0 +/- 3.8 kg) or Angus x Hereford (9.6 +/- 3.2 kg) progeny. Mature Angus x Hereford mothers weaned heavier calves than did Brahman x Herefords (7.4 +/- 3.2 kg, P less than .05) or Brahman x Angus (10.9 +/- 3.0 kg, P less than .01). Analysis of the Hereford-Red Poll diallel showed evidence of maternal heterosis in calf weaning weight (4.0 +/- 2.6 kg, P less than .05), but there was no difference in the percentage of calves weaned by crossbred vs straightbred dams.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332396 TI - Genetic implications of a simulation model of litter size in swine based on ovulation rate, potential embryonic viability and uterine capacity: I. Genetic theory. AB - A simulation model of litter size in swine based on ovulation rate, uterine capacity and potential embryo viability was compared to three genetic models to clarify its genetic characteristics. The simulation model is equivalent to independent culling based on fixed levels of potentially viable embryos and uterine capacity. Litter size also can be described by a combination of additive, additive x additive, mean environment x additive, random environment and additive x random environment effects. A third genetic model that can describe the simulation model is the associative effects model, in which litter size is the result of grouping two genotypes. The fixed independent culling levels model predicts that genetic parameters will change as the component means change. This genetic model also predicts that selection on an index of ovulation rate and uterine capacity would improve selection response for litter size. This genetic model predicts asymmetry of correlated responses in ovulation rate and uterine capacity when selecting for high and low litter size. The nonadditive genetic model predicts covariances among relatives that are different from their additive relationships; however, simulated results did not detect any differences. The nonadditive genetic model also predicts that heterosis for litter size will differ among crosses based on the mean environment and on additive x additive genetic interaction. The associative effects model predicts that selection for litter size will always lead to a positive response in litter size. PMID- 2332397 TI - Genetic implications of a simulation model of litter size in swine based on ovulation rate, potential embryonic viability and uterine capacity: II. Simulated selection. AB - Direct selection for ovulation rate, uterine capacity, litter size and embryo survival and selection for indexes of ovulation rate with each of the remaining traits were simulated for a swine population. The relationships among these traits were determined from a simulation model that assumed that litter size was always less than or equal to both ovulation rate and uterine capacity. Heritabilities of ovulation rate and uterine capacity were assumed to be .25 and .20, respectively, and uncorrelated genetically and phenotypically. No additional genetic variation was assumed. Responses to weak selection pressure were simulated by recurrent updating of phenotypic variances and covariances combined with the heritabilities of ovulation rate and uterine capacity. Two indexes of ovulation rate and uterine capacity each resulted in 37% greater increase in litter size than direct selection for litter size. Indexes of ovulation rate and either litter size or embryo survival increased litter size by 21% more than direct selection for litter size. Selection for ovulation rate, uterine capacity or embryo survival was 6, 35 and 79%, respectively, less effective than direct selection for litter size. Responses to intense selection pressure were determined by direct simulation of genotypes and phenotypes of individuals. The two indexes of ovulation rate and uterine capacity exceeded direct selection for litter size by 39 and 27%. The indexes of ovulation rate and either litter size or embryo survival exceeded direct selection for litter size by 19 and 13%, respectively. Intense selection for ovulation rate or uterine capacity decreased selection response by 26 and 67%, respectively, relative to direct selection for litter size. Intense selection for embryo survival decreased litter size slightly. PMID- 2332398 TI - Effect of age of exposure on consumption of a shrub by sheep. AB - We investigated the influence of age of exposure to a specific forage on its consumption by young sheep both during and after that exposure. Prior exposure to the shrub Cercocarpus montanus enhanced subsequent consumption (P less than or equal to .05) of that shrub by lambs and yearlings during two experiments in consecutive years. Effects of prior exposure persisted as long as 9 mo without intervening exposure. Age of exposure influenced consumption in lambs both during the period of exposure (P less than or equal to .0001) and during feeding trials following exposure (P less than or equal to .07) in Exp. 1. Lambs exposed at 1 to 5 wk of age, when they are nonruminant and normally are dependent on the dam, browsed less of the time while at the shrub (P less than or equal to .02) and consumed less of the shrub (P less than .02) at a slower rate (P less than or equal to .03) than did lambs exposed at older ages. Lambs exposed at 4 to 8 wk of age, a period corresponding to the transition from nonruminant to ruminant digestion, consumed more shrub following exposure than did lambs exposed at younger or older ages (P less than equal to .05, unprotected least significant differences test). In Exp. 2, which compared naive yearlings with the experienced yearlings exposed as lambs in Exp. 1 the previous year, age of exposure did not influence consumption by yearling sheep following exposure; however, the number of months that had elapsed from the period of exposure varied from 0 to 13 among experimental groups and may have confounded results. Learning of forages appeared poor among nonruminant lambs; data were inconclusive concerning the efficiency of learning of lambs in the transition to ruminant digestion. PMID- 2332399 TI - The establishment and persistence of food preferences in lambs exposed to selected foods. AB - Our study determined whether lambs' food preferences developed as a result of exposure to specific foods early in life and whether the presence of the mother affected the development of dietary preferences. In the first experiment, lambs were fed wheat (W) and mountain mahogany (MM) (Cercocarpus montanus) from 50 to 110 d of age. After exposure to W and MM, lambs preferred (P less than .05) W when offered with barley (B) but did not prefer (P greater than .05) MM when offered with serviceberry (SB) (Amelanchier alnifolia), probably because lambs were reluctant to eat mountain mahogany during exposure. Persistence was determined by dividing lambs exposed to W or MM into four groups: 1) continued exposure to W (MM); 2) exposure to B (SB); 3) no further exposure; and 4) exposure to W + B (MM +SB). Preferences for wheat persisted (P less than .05) regardless of the second exposure. In the second experiment, lambs were exposed to W (MM) either alone or with their mothers. Persistence was determined after 21 d of exposure to B (SB). Lambs preferred (P less than .05) W and MM whether they were exposed alone or with their mothers. However, preferences persisted longer in lambs exposed with their mothers. Finally, lambs exposed to either SB or MM with their mothers were later allowed to choose between SB or MM. Lambs strongly preferred (P less than .05) the shrub to which they were exposed early in life. PMID- 2332400 TI - Sequence analysis of the hutH gene encoding histidine ammonia-lyase in Pseudomonas putida. AB - The complete nucleotide sequence of the hutH gene, encoding histidine ammonia lyase (histidase), in Pseudomonas putida ATCC 12633 has been determined from the appropriate portions of the hut region that had been cloned into Escherichia coli. The resulting DNA sequence revealed an open reading frame of 1,530 base pairs, corresponding to a protein subunit of approximate molecular weight 53,600, in the location previously identified for the histidase gene by Tn1000 mutagenesis. Translation began at a GTG codon, but direct protein sequencing revealed that the initiating amino acid was removed posttranslationally to provide an N-terminal threonine; 11 additional residues completely agreed with the predicted amino acid sequence. This sequence excluded the possibility that a dehydroalanine unit, the postulated coenzyme for histidase, is attached at the N terminus of histidase subunits. Comparison of the P. putida histidase gene sequence with that of a Bacillus subtilis region encoding histidase revealed 42% identity at the protein level. Although the hutU (urocanase) and hutH (histidase) genes are induced by urocanate and normally are transcribed as a unit beginning with hutU, analysis of the region immediately upstream of the histidase gene revealed a potential weak promoter that may possibly be used to maintain a basal level of histidase for the generation of inducer (urocanate) when histidine levels are elevated. PMID- 2332401 TI - Teichuronic acid reducing terminal N-acetylglucosamine residue linked by phosphodiester to peptidoglycan of Micrococcus luteus. AB - Teichuronic acid-peptidoglycan complex isolated from Micrococcus luteus cells by lysozyme digestion in osmotically stabilized medium was treated with mild acid to cleave the linkage joining teichuronic acid to peptidoglycan. This labile linkage was shown to be the phosphodiester which joins N-acetylglucosamine, the residue located at the reducing end of the teichuronic acid, through its anomeric hydroxyl group to a 6-phosphomuramic acid, a residue of the glycan strand of peptidoglycan. 31P nuclear magnetic resonance spectroscopy of the lysozyme digest of cell walls demonstrated the presence of a phosphodiester which was converted to a phosphomonoester by the conditions which released teichuronic acid from cell walls. Reduction of acid-liberated reducing end groups by NaB3H4 followed by complete acid hydrolysis yielded [3H] glucosaminitol from the true reducing end residue of teichuronic acid and [3H]glucitol from the sites of fragmentation of teichuronic acid. The amount of N-acetylglucosamine detected was approximately stoichiometric with the amount of phosphate in the complex. Partial fragmentation of teichuronic acid provides an explanation of the previous erroneous identification of the reducing end residue. PMID- 2332402 TI - Characterization of Halobacterium halobium mutants defective in taxis. AB - Mutant derivatives of Halobacterium halobium previously isolated by using a procedure that selected for defective phototactic response to white light were examined for an array of phenotypic characteristics related to phototaxis and chemotaxis. The properties tested were unstimulated swimming behavior, behaviorial responses to temporal gradients of light and spatial gradients of chemoattractants, content of photoreceptor pigments, methylation of methyl accepting taxis proteins, and transient increases in rate of release of volatile methyl groups induced by tactic stimulation. Several distinct phenotypes were identified, corresponding to a mutant missing photoreceptors, a mutant defective in the methyltransferase, a mutant altered in control of the methylesterase, and mutants apparently defective in intracellular signaling. All except the photoreceptor mutant were defective in both chemotaxis and phototaxis. PMID- 2332403 TI - Characterization of a major 31-kilodalton peptidoglycan-bound protein of Legionella pneumophila. AB - A 31-kilodalton (kDa) protein was solubilized from the peptidoglycan (PG) fraction of Legionella pneumophila after treatment with either N-acetylmuramidase from the fungus Chalaropsis sp. or with mutanolysin from Streptomyces globisporus. The protein exhibited a ladderlike banding pattern by autoradiography when radiolabeled [( 35S]cysteine or [35S]methionine) PG material was extensively treated with hen lysozyme. The banding patterns ranging between 31 and 45 kDa and between 55 and 60 kDa resolved as a single 31-kDa protein when the material was subsequently treated with N-acetylmuramidase. Analysis of the purified 31-kDa protein for diaminopimelic acid by gas chromatography revealed 1 mol of diaminopimelic acid per mol of protein. When outer membrane PG material containing the major outer membrane porin protein was treated with N acetylmuramidase or mutanolysin, both the 28.5-kDa major outer membrane protein and the 31-kDa protein were solubilized from the PG material under reducing conditions. In the absence of 2-mercaptoethanol, a high-molecular-mass complex (100 kDa) was resolved. The results of this study indicate that a 31-kDa PG-bound protein is a major component of the cell wall of L. pneumophila whose function may be to anchor the major outer membrane protein to PG. Finally, a survey of other Legionella species and other serogroups of L. pneumophila suggested that PG bound proteins may be a common feature of this genus. PMID- 2332404 TI - Expression of the Agrobacterium tumefaciens chvB virulence region in Azospirillum spp. AB - Inner membranes of Azospirillum brasilense incubated with UDP-glucose were unable to synthesize beta-(1-2) glucan and lacked the 235-kilodalton intermediate protein known to be involved in the synthesis of beta-(1-2) glucan in Agrobacterium tumefaciens and Rhizobium meliloti. Inner membranes of A. brasilense strains carrying a cosmid containing the chromosomal virulence genes chvA and chvB of Agrobacterium tumefaciens formed beta-(1-2) glucan in vitro and synthesized the 235-kilodalton intermediate protein. No DNA homology to the chvB region was found in different wild-type strains of A. brasilense, but the introduction of a cosmid containing the Agrobacterium tumefaciens chvA and chvB regions yielded strains in which DNA hybridization with the chvB region was detected, provided that the strains were grown under an antibiotic selective pressure. PMID- 2332405 TI - Characterization of the surface layer glycoprotein of Clostridium symbiosum HB25. AB - The cell surface of Clostridium symbiosum HB25 is covered by a squarely arranged surface layer (S-layer) glycoprotein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the sodium dodecyl sulfate-soluble whole-cell extract showed the presence of several high-molecular-weight protein bands in a narrow range (approximate Mr, 140,000) which, upon periodic acid-Schiff staining, gave a positive reaction. After proteolytic degradation of the purified S-layer glycoprotein, a single glycopeptide fraction was obtained by gel permeation chromatography. Hydrolysis, treatment with aqueous hydrofluoric acid, and 1H and 13C nuclear magnetic resonance studies showed that the glycoprotein glycan is a high-molecular-weight polymer (approximate Mr, 15,000) of tetrasaccharide repeating units with the component sugars N-acetylgalactosamine (GalNAc), N acetylmannosamine (ManNAc), and N-acetylbacillosamine (BacNAc; 2-N-acetyl-4-amino 2,4,6-trideoxy glucose) linked by monophosphate diesters. The following structure is proposed: [----6)-alpha-D-ManpNAc-(1----4)-beta-D-GalpNAc-(1----3)-alpha-D-+ ++BacpNAc- (1----4)-alpha-D-GalpNAc-(1----PO3)----]n. The nuclear magnetic resonance data provided evidence for a charge interaction between the free amino group of BacNAc and the phosphate group of adjacent glycan chains. Since polycationic ferritin did not label the cell surface of intact cells, an electrostatic interaction can also be expected in vivo, leading to a charge neutral outer surface, which is characteristic of all other S layers from members of the family Bacillaceae studied so far. PMID- 2332406 TI - Effects of alfalfa nod gene-inducing flavonoids on nodABC transcription in Rhizobium meliloti strains containing different nodD genes. AB - Transcription of the nodulation genes nodABC in Rhizobium meliloti requires a plant flavonoid signal and nodD, a family of bacterial regulatory genes (nodD1, nodD2, and nodD3). Results from this study show that all previously identified nod gene inducers released by alfalfa seeds and roots induced nodABC-lacZ transcription in R. meliloti containing extra copies of nodD1, but only 4,4' dihydroxy-2'-methoxychalcone gave high levels of induction with extra copies of nodD2. While mixtures of the methoxychalcone and luteolin showed a positive synergism with extra NodD1 protein, they apparently competed for binding to the NodD2 protein. PMID- 2332407 TI - A Dictyostelium discoideum mutant exhibiting calcium-dependent, high-level detergent resistance. AB - We report the isolation of a mutant of the cellular slime mold Dictyostelium discoideum that is highly resistant to the lethal action of the nonionic detergent Triton X-100. The resistance is completely dependent on the presence of divalent cations, of which Ca2+ is the most effective. PMID- 2332408 TI - Occurrence of poly-beta-hydroxybutyrate in Spirulina species. AB - Several strains of photoautotrophically grown Spirulina spp. contained poly-beta hydroxybutyrate (PHB) at concentrations never exceeding a few milligrams per gram of dry weight. Under mixotrophic growth conditions in the presence of acetate, PHB reached values greater than 2.5% of dry weight. With pyruvate, no significant effect on PHB accumulation was obtained. PMID- 2332409 TI - Cloning and analysis of a 35.3-kilobase DNA region involved in exopolysaccharide production by Xanthomonas campestris pv. campestris. AB - Cosmid clones able to restore exopolysaccharide production in possibly insertion sequence element-induced surface mutants of Xanthomonas campestris pv. campestris were isolated. By fragment-specific Tn5-lac mutagenesis of one of the cosmids, pXCB1002, a new DNA region which is involved in exopolysaccharide biosynthesis and which is organized into at least 12 complementation groups was identified. PMID- 2332410 TI - A 57-kilodalton protein associated with Spiroplasma melliferum fibrils undergoes reversible phosphorylation. AB - Phosphorylation of a major 57-kilodalton protein substrate was observed in cell lysates of Spiroplasma melliferum BC3 incubated with [gamma-32P]ATP. Only serine phosphates have been isolated from the acid hydrolysate of the phosphorylated protein. The 57-kilodalton protein substrate was found, to a large extent, in the cytosolic fraction and, to a lesser extent, associated with cell membranes and was detected in the Triton X-100-insoluble fraction that contained fibrils. PMID- 2332411 TI - Inhibitory effect of tumor necrosis factor on gene expression of hormone sensitive lipase in 3T3-L1 adipocytes. AB - Recombinant human tumor necrosis factor (TNF) depressed the activities of both lipoprotein lipase (LPL) and hormone sensitive lipase (HSL) in 3T3-L1 adipocytes, 3 to 24 h after its introduction to the cells. HSL gene expression, as measured by Northern blotting analysis with 32P-labeled cloned HSL-cDNA, was also suppressed. These results suggested that the reduction in HSL activity caused by TNF resulted from inhibited gene expression of the enzyme. PMID- 2332412 TI - Purification and characterization of glutathione S-transferases from guinea pig liver. AB - Four types of glutathione S-transferase were purified to homogeneity from guinea pig liver by DEAE-cellulose, Sephadex G-75, CM-cellulose, and affinity chromatography. These isozymes were named a, b, c, and d based on the reverse order of elution from a CM-cellulose column, and had specific activities of 89.6, 92.2, 99.0, and 44.0 units/mg, respectively, when assayed with 1 mM each of 1 chloro-2,4-dinitrobenzene and reduced glutathione. All four transferases of guinea pig liver were homodimers. The transferases b, c, and d had a similar molecular weight of 50,000 and their subunit sizes were 25,000, but the corresponding values for transferase a were 45,000 and 23,500, respectively. Transferase a was notably different in the activities towards organic hydroperoxides and 1,2-dichloro-4-nitrobenzene from the other isozymes. Transferases a and b, the major forms in guinea pig liver, were studied with respect to their biochemical properties, including kinetic parameters, absorption and fluorescence spectra, and bilirubin binding. Glutathione peroxidase activity of the transferase a was about 100 times higher than that of other isozymes. In guinea pig liver, it is estimated that transferase a is the major glutathione peroxidase, accounting for about 75% of the total organic hydroperoxide reduction. PMID- 2332413 TI - Amino acid sequence of glutathione S-transferase b from guinea pig liver. AB - The amino acid sequence of glutathione S-transferase b (GST b) from guinea pig liver was determined by conventional methods. GST b was composed of two identical subunits, each with 217 amino acid residues. As GSTs are generally classified into three classes, alpha, mu, and pi, GST b belonged to class mu and the amino acid sequence of GST b showed about 80% homology with that of rat GST Yb. PMID- 2332414 TI - Calorimetric studies on calcium and magnesium binding by troponin C from bullfrog skeletal muscle. AB - Microcalorimetic titrations were carried out to measure the thermodynamic functions of bullfrog skeletal muscle troponin C (TnC) in the interaction with Ca2+ and Mg2+, at 25 degrees C and at pH 7.0. Enthalpy titration curves with Ca2+ were composed of three stages both in the presence and in the absence of Mg2+. The first (0-2 mol Ca2+/mol TnC) and the third (greater than 3 mol Ca2+/mol TnC) stages were exothermic and the second stage (2-3 mol Ca2+/mol TnC) was endothermic. Mg2+ affected the first stage to decrease the amount of heat produced but not the second and third stages. The enthalpy titration with Mg2+, in the absence of Ca2+, was slightly exothermic initially and then became endothermic beyond 2-3 mol Mg2+/mol TnC. Absorption of heat was observed throughout the additions of Mg2+ in the presence of 1 mM Ca2+. The results indicate that bullfrog TnC has two high-affinity Ca2+-Mg2+ sites, two low affinity Ca2(+)-specific sites, and two or around two Mg2(+)-specific sites. Based on the enthalpy and entropy changes, the Ca2+ binding reactions of TnC were classified into three types, indicating thermodynamic variety in the binding sites of the molecule. PMID- 2332415 TI - Large-scale purification of bovine brain lactate dehydrogenase by affinity chromatography on immobilized colchicine. AB - Lactate dehydrogenase (LDH) [EC 1.1.1.27] in a crude extract (40-80% ammonium sulfate fraction) of bovine brain was adsorbed on an immobilized colchicine column and specifically eluted by addition of 1 mM NADH. The purity and subunit composition of the pooled LDH were estimated by two-dimensional gel electrophoresis. With an increase of NaCl concentration from 0 to 2.0 M, ligand saturation of LDH on immobilized colchicine increased from 6.8 to 14%, whereas that on immobilized Cibacron blue F3GA decreased from 2.1 to 0%. In the presence of high NaCl concentration, immobilized colchicine enabled both large- and small scale purification of LDH by affinity chromatography and resulted in a yield of 117 mg from 1 kg of bovine brain in the presence of 2.5 M NaCl or higher recoveries of 54-96% from various tissues of one rat in the presence of 1.0 M NaCl. These results indicate that immobilized colchicine is an excellent adsorbent for the isolation and purification of LDH by affinity chromatography and has a high LDH-adsorbing capacity dependent upon a high NaCl concentration. Kinetic studies revealed that colchicine apparently competed with cofactor NAD for the active site of LDH and the Ki values of colchicine decreased with an increase of NaCl concentration. The chemical specificity of the colchicine binding site of LDH was studied by the use of colchicine analogues and it is concluded that both the tropolone moiety (C-ring) and the amido bond in a side chain of colchicine structure are essential to the colchicine-LDH interaction. PMID- 2332416 TI - Conservative segregation of tetrameric units of H3 and H4 histones during nucleosome replication. AB - We have specifically investigated the behavior of H3 and H4 histones during the replication cycle of MH-134SC cells. Mononucleosomes obtained from cells density labeled with IdU or dense amino acids in the presence of appropriate radiolabeled precursors were applied to sucrose gradients containing 0.3 M NaCl and 4 M urea for rate zonal centrifugation. This allowed the resolution of dense and normal subnucleosome particles composed of DNA and two molecules each of H3 and H4 without any measurable interparticle histone exchange. On labeling with dense amino acids and radiolabeled lysine, a distinct peak of radiolabeled dense particles was obtained. In contrast, pre-radiolabeled H3 and H4 remained in the normal subnucleosome peak region even after one generation time of culturing with dense amino acids. These data indicate the formation of (H3-H4)2 tetramers composed entirely of new H3 and H4 molecules as well as the conservation of pre existing tetramers. Density labeling for 1 h with IdU in the presence of radiolabeled lysine yielded a distinct peak of radiolabeled dense particles, indicating the deposition of new tetramers on newly replicated DNA. Similar rate zonal analysis of subnucleosome particles obtained from cells prelabeled for 1 h with radiolabeled lysine followed by various IdU-labeling schedules in nonisotopic media yielded data suggesting that tetramers once deposited do not move about randomly during the replication cycle. A possible mode of nucleosome replication is discussed in the light of the present data. PMID- 2332417 TI - Distribution of aspartate aminotransferase activity in yeasts, and purification and characterization of mitochondrial and cytosolic isoenzymes from Rhodotorula minuta [corrected]. AB - The distribution of aspartate aminotransferase activity in yeasts was determined. The number of species of the enzyme in each yeast was determined by zymogram analysis. All the yeasts, except for the genus Saccharomyces, showed two or three activity bands on a zymogram. From among the strains, Rhodotorula minuta [corrected] and Torulopsis candida were selected for examination of the existence of yeast mitochondrial isoenzymes, because these strains showed two clear activity bands on the zymogram and contained a high amount of the enzyme. Only one aspartate aminotransferase was purified from T. candida: the component in the minor band on the zymogram was not an isoenzyme of aspartate aminotransferase. On the other hand, two aspartate aminotransferases were purified to homogeneity from R. minuta [corrected]. The components in the main and minor activity bands on the zymogram were identified as the mitochondrial and cytosolic isoenzymes, respectively, in a cell-fractionation experiment. The enzymatic properties of these isoenzymes were determined. The yeast mitochondrial isoenzyme resembled the animal mitochondrial isoenzymes in molecular weight (subunits and native form), absorption spectrum, and substrate specificity. The amino acid composition was closely similar to that of pig mitochondrial isoenzyme. Rabbit antibody against the yeast mitochondrial isoenzyme, however, did not form a precipitin band with the pig mitochondrial isoenzyme. PMID- 2332418 TI - The NH2-terminal 14-16 amino acids of mitochondrial and bacterial thiolases can direct mature ornithine carbamoyltransferase into mitochondria. AB - Unlike most mitochondrial matrix proteins, the mitochondrial 3-oxoacyl-CoA thiolase [EC 2.3.1.16] is synthesized with no cleavable presequence and possesses information for mitochondrial targeting and import in the mature protein. This mitochondrial thiolase is homologous with the mature portion of peroxisomal 3 oxoacyl-CoA thiolase and acetoacetyl-CoA thiolase [EC 2.3.1.9] of Zoogloea ramigera along the entire sequence. A hybrid gene encoding the NH2-terminal 16 residues (MALLRGVFIVAAKRTP) of the mitochondrial thiolase fused to the mature portion of rat ornithine carbamoyltransferase [EC 2.1.3.3] (lacking its own presequence) was transfected into COS cells, and subcellular localization of the fusion protein was analyzed. Cell fractionation and immunocytochemical analyses showed that the fusion protein was localized in the mitochondria. These results indicate that the NH2-terminal 16 residues of the mitochondrial thiolase function as a noncleavable signal for mitochondrial targeting and import of this enzyme protein. The fusion protein containing the NH2-terminal 14 residues (MSTPSIVIASARTA) of the bacterial thiolase was also localized in the mitochondria. On the other hand, the fusion protein containing the corresponding portion (MQASASDVVVVHGQRTP) of the peroxisomal thiolase appeared not to be localized to the mitochondria. These results show that the import signal of mitochondrial 3-oxoacyl-CoA thiolase originated from the NH2-terminal portion of the ancestral thiolase. The ancestral enzyme might have already possessed a mitochondrial import activity when mitochondria appeared first, or that it might have acquired the import activity during evolution by accumulation of point mutations in the NH2-terminal portion of the enzyme. PMID- 2332419 TI - Genetic regulation of GM4(NeuAc) expression in mouse erythrocytes. AB - The polymorphic expression of GM4(NeuAc), GM3(NeuGc), GM2(NeuGc), and GM1(NeuGc) was found in erythrocytes of inbred strains of mice [Nakamura, K. et al. (1988) J. Biochem. 103, 201-208]. In this paper, we report the results of genetic analysis of the expression of GM4(NeuAc) and GM2(NeuGc). Ganglioside analysis of the progeny obtained on mating between BALB/c mice [GM4 (+)] and WHT/Ht or C57BL/6 mice [both GM4 (-)] indicated that the expression of GM4(NeuAc) is an autosomal dominant trait, and that WHT/Ht and C57BL/6 mice carry a defect on a single autosomal gene. We named this gene Gsl-4. On quantitative determination of galactosylceramide (GalCer), which is the biosynthetic precursor of GM4(NeuAc), the content of GalCer was found to be quite low in WHT/Ht erythrocytes, compared with in BALB/c erythrocytes. On analysis of GM4(NeuAc) and GalCer in 92 backcross mice produced on mating between BALB/c and WHT/Ht mice, it was found that 45 GM4(+) mice apparently expressed a detectable amount of GalCer and that 47 GM4(-) mice expressed an almost undetectable amount of GalCer. These results suggest that Gsl-4 controls the expression of GM4(NeuAc) by regulating the content of GalCer. Linkage analysis of Gsl-4 and the gene controlling GM2(NeuGc) in erythrocytes indicated that the two genes are not genetically linked. Comparison of the ganglioside expression in liver and erythrocytes of the same backcross mice suggested that the gene controlling GM2(NeuGc) expression in the liver (Ggm 2) is also responsible for the expression of GM2(NeuGc) in erythrocytes. PMID- 2332420 TI - Detection and isolation of a 30 kDa abnormal protein in avian dystrophic muscle. AB - We have studied the protein composition of the pectoralis superficialis muscle of genetically dystrophic (New Hampshire line 413) and normal control (line 412) chickens by one- and two-dimensional gel electrophoresis. A protein, referred to hereafter as the 30 kDa abnormal protein, was specifically detected in the affected muscle. It was purified to homogeneity, and its molecular properties were studied. It is a monomer with a molecular mass of approximately 30 kDa and an isoelectric point of about pI 8.4. We have screened by Western blotting a variety of muscles from line 412 and line 413 chickens for the presence of the 30 kDa protein. While the pattern of total protein is very similar in all cases, the 30 kDa protein was not detected in the pectoralis superficialis muscle of line 412 chickens. However, the immunoreactive bands were detected in the sartorius muscle and the tensor fasciae latae muscle from dystrophic and normal chickens. Interestingly, the immunoreactive bands of normal skeletal muscles are smaller in molecular weight than those of dystrophic skeletal muscles. To determine the early time sequence of the appearance of the abnormal protein, we studied muscles from embryos and post-hatched chickens at various ages. The abnormal protein was detected in dystrophic muscles as early as 15 days ex ovo and occurred throughout development up to six months ex ovo. Although the implication of the dystrophy associated appearance of the 30 kDa protein in the affected muscle is not clear at present, it would be of particular interest to elucidate the biochemical functions of the 30 kDa protein in the affected muscle (pectoralis superficialis muscle) of genetically dystrophic chicken. PMID- 2332421 TI - Molecular cloning and characterization of cDNAs coding for apopolysialoglycoproteins in cherry salmon (Oncorhynchus masou) eggs. AB - Recently we have cloned the cDNAs and genomic DNAs for apopolysialoglycoproteins (apoPSGPs) of Salmo gairdneri (rainbow trout) [Sorimachi, H., Emori, Y., Kawasaki, H., Kitajima, K., Inoue, S., Suzuki, K., & Inoue, Y. (1988) J. Biol. Chem. 262, 17678-17684], and the sequence analyses have indicated that the mRNAs for apoPSGPs vary in length and contain different numbers of identical 39-bp repeating units encoding the tridecapeptide (Asp-Asp-Ala-Thr-Ser-Glu-Ala-Ala-Thr Gly-Pro-Ser-Gly) as well as highly conserved sequences encoding pre-, pro-, and telo-peptide regions. In this study we isolated cDNA clones for yamame (cherry salmon, river resident form; Oncorhynchus masou ishikawai) apoPSGP using a genomic DNA fragment for rainbow trout apoPSGP as a probe. The nucleotide sequence analyses revealed that the structures of mRNAs for yamame apoPSGP including the noncoding regions are essentially identical to those for rainbow trout, showing 90% sequence identity. Within the repeating region, 4 bp out of the 39 were replaced, producing a different tridecapeptide, Asp-Asp-Ala-Thr-Ser Glu-Ala-Ala-Thr-Gly-Pro-Ser-Ser. This tridecapeptide is unique to yamame and common among all cDNAs obtained from yamame. Genomic Southern blot analysis showed that the yamame apoPSGP genes constituted a multiple gene family with a similar gene organization to that of rainbow trout. Oligodeoxynucleotide probes (18 bases) synthesized based on specific sequences for the yamame repeating unit hybridized only to the yamame DNA and not to the rainbow trout DNA, and vice versa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332422 TI - Structural organization of the bovine adrenodoxin gene. AB - The gene structure of bovine adrenodoxin (Ad), a component of the steroid hydroxylating system in adrenal cortex mitochondria, was determined. This gene seems to be a single copy, but contains a pseudo exon in addition to the genuine gene region. The gene region for the active Ad is divided into 4 exons by 3 introns, and spans at least 27 kb. All the splice donor and acceptor sites follow the GT/AG rule. The transcription initiation site was determined by primer extension analysis, and putative TATA and GC boxes are present in the 5'-flanking region. A 12 base sequence, CCAGGGCCAGGG, is present 95 bases upstream from the transcription initiation site. A similar sequence was also found in the 5' flanking regions of all genes for the steroid hydroxylating cytochromes P-450: P 450(SCC), P-450(11 beta), P-450(17 alpha), and P-450(C21), in the adrenal cortex. The consensus sequence for these five sequences is CGCAGGGCCATGGGA. The pseudo exon, exon 1', was present about 0.5 kb upstream from exon 1. It encodes the prepeptide region of the minor type Ad mRNA, but has a stop codon (TAA) in the frame. A TATA-box-like sequence and a CAAT-box-like sequence are also present in the 5'-flanking region of exon 1'. The GC content of exon 1 was over 80%, whereas for each of the other four exons, including exon 1', it was about 40%. Our observations suggest that exon 1, which encodes the prepeptide region of the major type Ad mRNA, has intruded into the region between exon 1' and exon 2. PMID- 2332423 TI - Glycosphingolipid patterns of peripheral blood lymphocytes, monocytes, and granulocytes are cell specific. AB - We analyzed the amounts and types of glycosphingolipids (GSLs) from peripheral blood lymphocytes, monocytes, and granulocytes isolated by counter-current elutriation. The three cell types contained different amounts of neutral and acidic GSLs. The highest amount of neutral GSLs (109 micrograms/10(8) cells) was found in granulocytes, with considerably less found in monocytes (11 micrograms/10(8) cells) and lymphocytes (4 micrograms/10(8) cells). The neutral GSLs were composed of four types of lipids, GL1 through GL4 (mono-, di-, tri-, and tetraosylceramide). The highest percentage of GL1 was detected in lymphocytes and the lowest percentage in granulocytes, with the reverse order observed for GL2. GL3 and GL4, which were minor components of the neutral GSLs, were highly cell specific, with lymphocytes containing GL3 and GL4 of the globo series, granulocytes containing GL3 and GL4 of the lacto or neolacto series, and monocytes containing GL3 and GL4 of both types. The acidic GSL, sialosyl hexaosylceramide (lacto-series), was abundant in granulocytes but not in monocytes or lymphocytes. Another ganglioside, GM3, although present in all three cell types, was most abundant in monocytes and lymphocytes, whereas sialosyl paragloboside was higher in granulocytes than in lymphocytes and monocytes. These results indicate that peripheral blood lymphocytes, monocytes, and granulocytes have distinct "GSL fingerprints." PMID- 2332424 TI - Preliminary crystallographic study of phospholipase A2 from the venom of Trimeresurus flavoviridis (habu snake). AB - Crystallization and a preliminary crystallographic study of Trimeresurus flavoviridis (habu snake) phospholipase A2 (PLA2) were carried out. Although crystals were obtained from various solutions, crystals suitable for X-ray analysis could be obtained from polyethylene glycol solutions only when a repeated seeding technique was applied starting from twinned crystals. The crystal is monoclinic with space group P21, with a = 44.1, b = 55.7, c = 48.8 A, and beta = 92.4 degrees. An asymmetric unit contains a dimer consisting of two identical subunits made of 122 amino acids. The crystal reflects X-rays beyond 2.5 A. A Pt derivative gave a good isomorphous crystal. PMID- 2332425 TI - Conversion of cholesterol to pregnenolone mobilizes cytochrome P-450 in the inner membrane of adrenocortical mitochondria: protein rotation study. AB - Rotation of cytochrome P-450 was examined in bovine adrenocortical mitochondria before and after an enzymatic transformation of cholesterol into pregnenolone by cytochrome P-450scc in the presence of malate. Rotational diffusion was measured by observing the decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about-membrane normal" model. The measurements were used to investigate substrate-dependent intermolecular interactions of cytochrome P-450 with other redox components. Rotational mobility of cytochrome P-450 was significantly dependent on the decrease in cholesterol content by side chain cleavage reaction catalyzed by cytochrome P-450scc. In a typical experiment, the observed value for the normalized time-independent anisotropy r(infinity)/r(0) was decreased from 0.78 in control mitochondria to 0.60 after conversion of 21% of cholesterol to pregnenolone, while no significant change was observed for the average rotational relaxation time phi of about 700 microseconds. Significantly high values of r(infinity)/r(0) = 0.78 and 0.60 imply co-existence of mobile and immobile populations of cytochrome P-450. Since we observed that the heme angle tilted 55 degrees from membrane plane, 22% (control mitochondria) and 40% (after conversion of cholesterol to pregnenolone) of cytochrome P-450 in mitochondria are calculated to be mobile in the preparation. The significant mobilization of cytochrome P-450scc molecules caused by the conversion of cholesterol to pregnenolone is likely due to changes in protein-protein interactions with its redox partners, since the lipid fluidity was kept unchanged by the cholesterol depletion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332426 TI - The major non-integrin laminin binding protein of macrophages is identical to carbohydrate binding protein 35 (Mac-2). AB - Current data indicate that cell adhesion to laminin, the major basement membrane glycoprotein, is mediated by specific integrins, a family of adhesion receptors. In addition, most cell types express a complement of high affinity non-integrin laminin binding proteins (LBPs). Despite considerable effort, the function of these LBPs has not been elucidated. We report here that the major non-integrin LBP of murine macrophages exhibits an Mr of 35,000 and is expressed on the cell surface. Protein microsequencing data revealed that this protein is identical to carbohydrate binding protein 35. This murine galactose-specific lectin is the macrophage antigen Mac-2. Thus, these data suggest that the non-integrin LBPs may contribute to laminin adhesion by a mechanism involving protein-carbohydrate interactions. PMID- 2332427 TI - Substrate stimulation of 7 alpha-hydroxylase, an enzyme located in the cholesterol-poor endoplasmic reticulum. AB - We examined the role of cholesterol in altering the activity of the microsomal cytochrome P-450 enzyme, cholesterol-NADPH:oxygen oxidoreductase (cholesterol 7 alpha-hydroxylase). Liposomes were used to deliver cholesterol to hepatic microsomes. Formation of 7 alpha-hydroxycholesterol was quantitated by isotope dilution/gas chromatography-mass spectrometry. As the liposomal cholesterol/phospholipid molar ratio increased, 7 alpha-hydroxylase activity increased, whereas the activity of another microsomal cytochrome P-450 enzyme, ethylmorphine N-demethylase, decreased. To determine if the degree of stimulation was affected by the endogenous activity (without liposomes), microsomes, from rats fed chow alone or chow containing cholestyramine, taurocholate, or cholesterol were challenged with cholesterol-enriched liposomes. The degree of stimulation was dependent upon the endogenous activity: cholestyramine-fed much greater than cholesterol = chow control greater than taurocholate-fed. To determine if cholesterol stimulates 7 alpha-hydroxylase by increasing membrane viscosity, microsomes were incubated with liposomes having the same cholesterol/phospholipid molar ratio as microsomes, but different viscosities. Dipalmitoylphosphatidylcholine (high viscosity) liposomes increased microsomal viscosity and decreased 7 alpha-hydroxylase activity. In contrast, dioleoylphosphatidylcholine (low viscosity) liposomes decreased microsomal viscosity and increased enzyme activity. Since greater viscosity inhibits 7 alpha hydroxylase, cholesterol cannot stimulate the enzyme by increasing membrane viscosity. The data suggest that cholesterol stimulates production of 7 alpha hydroxycholesterol by providing substrate. PMID- 2332428 TI - Stabilization of the mRNA follows transcriptional activation of type II collagen gene in differentiating chicken chondrocyte. AB - The differentiation of chicken endochondral chondrocyte can be induced in vitro by transferring to suspension culture dedifferentiated chondrocytes grown as adherent cells. During the differentiation process, the synthesis of type I collagen is repressed while the genes encoding type II, IX, and X collagens are gradually activated. The changes in the steady-state levels of the mRNAs for type I, IX, and X collagens were shown to be fully accounted for by proportional modifications in the rates of specific gene transcription (Castagnola, P., Dozin, B., Moro, G., and Cancedda, R. (1988) J. Cell Biol. 106, 461-467). In the present report, we demonstrate that the cellular accumulation of type II collagen mRNA in differentiating chondrocyte is regulated not only at the transcription level but also through a stabilization of the RNA transcript as shown by the enhanced half life of the mRNA in differentiated cells treated with actinomycin D. We also give evidence that this additional mechanism: 1) is specific for type II collagen, 2) does not occur at an early stage of differentiation when type II collagen mRNA starts accumulating, 3) affects only the cytoplasmic form of the RNA transcript. PMID- 2332429 TI - Phospholipid synthesis in a membrane fraction associated with mitochondria. AB - A crude rat liver mitochondrial fraction that was capable of the rapid, linked synthesis of phosphatidylserine (PtdSer), phosphatidylethanolamine (PtdEtn), and phosphatidylcholine (PtdCho) labeled from [3-3H] serine has been fractionated. PtdSer synthase, PtdEtn methyltransferase, and CDP-choline:diacylglycerol cholinephosphotransferase activities were present in the crude mitochondrial preparation but were absent from highly purified mitochondria and could be attributed to the presence of a membrane fraction, X. Thus, previous claims of the mitochondrial location of some of these enzymes might be explained by the presence of fraction X in the mitochondrial preparation. Fraction X had many similarities to microsomes except that it sedimented with mitochondria (at 10,000 x g). However, the specific activities of PtdSer synthase and glucose-6-phosphate phosphatase in fraction X were almost twice that of microsomes, and the specific activities of CTP:phosphocholine cytidylyltransferase and NADPH:cytochrome c reductase in fraction X were much lower than in microsomes. The marker enzymes for mitochondria, Golgi apparatus, plasma membrane, lysosomes, and peroxisomes all had low activities in fraction X. Polyacrylamide gel electrophoresis revealed distinct differences, as well as similarities, among the proteins of fraction X, microsomes, and rough and smooth endoplasmic reticulum. The combined mitochondria fraction X membranes can synthesize PtdSer, PtdEtn, and PtdCho from serine. Thus, fraction X in combination with mitochondria might be responsible for the observed compartmentalization of a serine-labeled pool of phospholipids previously identified (Vance, J. E., and Vance, D. E. (1986) J. Biol. Chem. 261, 4486-4491) and might be involved in the transfer of lipids between the endoplasmic reticulum and mitochondria. PMID- 2332430 TI - Biosynthesis of heparin. Availability of glucosaminyl 3-O-sulfation sites. AB - Heparin preparations isolated from pig intestinal mucosa and from bovine lung were fractionated with regard to affinity for antithrombin. The resulting fractions, with high (HA) or low (LA) affinity for the proteinase inhibitor, were analyzed by 13C NMR or by identification of di- and tetrasaccharides obtained through deaminative cleavage with nitrous acid. Structural differences between corresponding HA and LA fractions were essentially restricted to minor constituents, in particular 3-O-sulfated glucosamine units that occurred (1 or 2 residues/chain) in all HA preparations but were scarce or absent in LA heparin. The HA fractions also consistently showed higher contents of nonsulfated iduronic acid and, to a lesser extent, N-acetylated glucosamine units than the LA fractions. The two tetrasaccharide sequences, -IdoA-GlcNAc(6-OSO3)-GlcA-GlcNSO3- and -IdoA-GlcNAc(6-OSO3)-GlcA-GlcNSO3(6-OSO3)- , recently implicated as part of the acceptor site for glucosaminyl 3-O-sulfate groups (Kusche, M., Backstrom, G., Riesenfeld, J., Petitou, M., Choay, J., and Lindahl, U. (1988) J. Biol. Chem. 263, 15474-15484), were identified in mucosal LA heparin; it was calculated that the preparation contained approximately one potential acceptor site/polysaccharide chain. Yet this material did not yield any labeled HA components on incubation with adenosine 3'-phosphate 5'-phospho-[35S]sulfate in the presence of glucosaminyl 3-O-sulfotransferase, solubilized from a mouse mastocytoma microsomal fraction. The failure to incorporate any 3-O-sulfate groups could conceivably be explained by the occurrence of a D-glucuronic rather than L-iduronic acid unit linked at the reducing ends of the above tetrasaccharide sequences. Alternatively, 3-O-sulfation may be restricted by other, as yet unidentified, inhibitory structural elements that are preferentially expressed in polysaccharide sequences selected for the generation of LA heparin. PMID- 2332431 TI - Localization of the diphtheria toxin receptor-binding domain to the carboxyl terminal Mr approximately 6000 region of the toxin. AB - The carboxyl-terminal Mr = 5982 peptide of diphtheria toxin was prepared by specific cleavage of the toxin with hydroxylamine and purified by fast performance liquid chromatography. The identity of the peptide was established by a combination of sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, reactivity with specific monoclonal antibodies, and amino-terminal sequence analysis. The Mr = 5982 peptide was shown to protect highly toxin sensitive Vero cells from the lethal action of diphtheria toxin. This protection was shown to be due to inhibition of the initial step in the cytotoxic process, the binding of toxin to its receptor. These results strongly suggest that the Mr = 5982 carboxyl-terminal region (amino acid residues 482-535) is, or contains, the receptor-binding domain of diphtheria toxin. PMID- 2332432 TI - Mammalian and avian liver phosphoenolpyruvate carboxykinase. Alternate substrates and inhibition by analogues of oxaloacetate. AB - Phosphoenolpyruvate carboxykinase from chicken liver mitochondria and rat liver cytosol catalyzes the phosphorylation of alpha-substituted carboxylic acids such as glycolate, thioglycolate, and DL-beta-chlorolactate in reactions with absolute requirements for divalent cation activators. 31P NMR analysis of the reaction products indicates that phosphorylation occurs at the alpha-position to generate the corresponding O- or S-bridged phosphate monoesters. In addition, the enzymes catalyze the bicarbonate-dependent phosphorylation of hydroxylamine. The chicken liver enzyme also catalyze the bicarbonate-dependent phosphorylation of hydroxylamine. The chicken liver enzyme also catalyzes the bicarbonate-dependent phosphorylation of fluoride ion. The kappa cat values for these substrates are 20 1000-fold slower than the kappa cat for oxaloacetate. Pyruvate and beta hydroxypyruvate are not phosphorylated, since the enzyme does not catalyze the enolization of these compounds. Oxalate, a structural analogue of the enolate of pyruvate, is a competitive inhibitor of phosphoenolpyruvate carboxykinase (Ki of 5 microM) in the direction of phosphoenolpyruvate formation. Oxalate is also an inhibitor of the chicken liver enzyme in the direction of oxaloacetate formation and in the decarboxylation of oxaloacetate. The chicken liver enzyme is inhibited by beta-sulfopyruvate, an isoelectronic analogue of oxaloacetate. The extensive homologies between the reactions catalyzed by phosphoenolpyruvate carboxykinase and pyruvate kinase suggest that the divalent cation activators in these reactions may have similar functions. The substrate specificity indicates that phosphoenolpyruvate carboxykinase decarboxylates oxaloacetate to form the enolate of pyruvate which is then phosphorylated by MgGTP on the enzyme. PMID- 2332433 TI - Identification of a thyroid hormone response element in the malic enzyme gene. AB - We have studied the rat malic enzyme gene as a model for thyroid hormone (triiodothyronine (T3)) regulation of transcription. Our previous studies showed that transcription of this gene is controlled by T3 in vivo. In this study, we used COS-7 cells in culture to determine the location of a T3 response element (TRE) within this gene. Cotransfection of the rat T3 alpha-receptor cDNA with a reporter gene linked to 5'-deletion mutants of the malic enzyme gene 5'-flanking region revealed the presence of a TRE between positions -315 and -248. Using T3 receptors synthesized in vitro from their cDNAs, we have identified, through the use of gel shift assays and footprinting, a single DNA-binding site (positions 281 to -261) for the receptor within the rat malic enzyme gene TRE. The site was capable of binding either the rat alpha- or human beta-receptor with similar affinities. Competition binding studies indicated that the apparent affinity of receptor binding to the malic enzyme gene was similar to that of the rat alpha myosin heavy chain gene TRE (positions -151 to -122) and was significantly greater than that of the rat growth hormone TRE (positions -192 to -163). These results indicate that both the alpha- and beta-forms of the nuclear T3 receptor are capable of binding directly to the malic enzyme gene 5'-flanking region at a site which functions as a hormone-inducible cis-regulatory element. In conjunction with our previous finding that T3 induces or activates essential transcription factors which bind to the promoter, it appears that the regulation of transcription of the malic enzyme gene by thyroid hormone involves at least two regulatory pathways. PMID- 2332434 TI - The disulfide structure of mouse lysosome-associated membrane protein 1. AB - The disulfide structure of mouse lysosome-associated membrane protein 1 has been determined by reverse-phase isolation and sequence analysis of the cysteine containing tryptic fragments of the reduced and non-reduced deglycosylated protein. Half-cystines were distinguished (a) by their localization within tryptic or chymotryptic peptides that formed reverse-phase peaks unique to the reduced digests and (b) by their 3H-carboxymethylation only after reduction of the protein. The disulfide arrangement of the cysteines was assigned after isolation of disulfide-linked peptide pairs. Each pair chromatographed as a peak present in the nonreduced (but not the corresponding reduced) tryptic digest. NH2 terminal sequencing as well as reduction, alkylation, and rechromatography of the disulfide-linked fragments led to the following assignment of disulfide bonds: Cys11 and Cys50, Cys125 and Cys161, Cys198 and Cys235, and Cys303 and Cys340. This structure creates four 36-38-residue loops that are symmetrically placed within the two halves of the protein's intraluminal domain. The loops formed by the Cys11-Cys50 and Cys198-Cys235 bridges are homologous, and the Cys125-Cys161 and Cys303-cys340 loops form a second set of homologous domains. The conservation of cysteine residues among lysosome-associated membrane proteins 1 and 2 suggests that this disulfide arrangement is common to both members of this family of lysosomal membrane glycoproteins. PMID- 2332435 TI - Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues. The reg protein, pancreatic stone protein, and pancreatic thread protein are one and the same product of the gene. AB - We previously identified a novel gene, reg (i.e. regenerating gene), in the screening of a rat regenerating islet-derived cDNA library, and isolated its human cDNA homologue which encodes a 166-amino acid protein (Terazono, K., Yamamoto, H., Takasawa, S., Shiga, K., Yonemura, Y., Tochino, Y., and Okamoto, H. (1988) J. Biol. Chem. 263, 2111-2114). In the present study, we have isolated the human reg gene, determined its complete nucleotide sequence, and examined its expression in human tissues. The functional human reg gene is a single copy gene, spans approximately 3.0 kilobase pairs, and is composed of six exons and five introns. TATA box and CCAAT box-like sequences are located at 27 and 100 base pairs upstream from the transcriptional initiation site. The human reg mRNA was detected predominantly in the pancreas, and at lower levels in the gastric mucosa and the kidney. Furthermore, the reg gene was found to be expressed ectopically in colon and rectal tumors. Immunoblot analysis demonstrated several molecular forms (15-18 kDa) of the reg protein in the pancreas. The 166-amino acid sequence encoded by the human reg gene contains the 144-amino acid sequence of pancreatic stone protein determined by De Caro et al. (De Caro, A. M., Adrich, Z., Fournet, B., Capon, C., Bonicel, J. J., De Caro, J. D., and Rovery, M. (1989) Biochim. Biophys. Acta 994, 281-284) and the partially determined 45-amino acid sequence of pancreatic thread protein (Gross, J., Carlson, R. I., Brauer, A. W., Margolies, M. N., Warshaw, A. L., and Wands, J. R. (1985) J. Clin. Invest. 76, 2115-2126), indicating that the reg protein, pancreatic stone protein, and pancreatic thread protein are simply different names for a single protein deriving from the reg gene. PMID- 2332436 TI - A new concept of fibrin formation based upon the linear growth of interlacing and branching polymers and molecular alignment into interlocked single-stranded segments. AB - In a previous electron microscopic study of early fibrin polymers processed by freeze drying and rotatory shadowing, a large proportion of loosely constructed, frequently branching linear molecular chains was observed; their structural organization was inconsistent with a half-staggered double-stranded model for fibrin polymerization. These conflicting results prompted us to investigate the structure of early fibrin polymers prepared according to a large variety of methods currently used for electron microscopy of macromolecules. By use of a systematic random sampling procedure, fibrin polymers were photographically recorded. They were classified according to their morphological form, and the frequency of occurrence of each configuration was determined. Half-staggered double-stranded forms accounted for less than 1% of all types encountered. Interpretation of the structural organization manifested in the diverse polymer forms observed necessitated the construction of a new interlocked single-strand model for fibrin polymerization. The fibrin polymerization process combines simultaneous propagation of linear growth, branching, and lateral interlocking (leading to lateral association), resulting in the rapid formation of a fibrin network. The structural pattern developing during growth of fibrin polymers appears to be determined principally by the enzymatic mechanism and not solely by the intrinsic molecular structure of fibrinogen. The validity of the interlocked single-strand model was tested by selective fibrinopeptide-B-releasing experiments. Under such activation conditions, the polymer forms predicted according to this and the half-staggered double-strand models should differ; the structures observed were indeed consistent with the interlocked single-strand hypothesis. The compatibility of existing data with this model is discussed. PMID- 2332437 TI - A transcription stimulatory factor binds to the upstream region of Xenopus 5 S RNA and tRNA genes. AB - Upstream sequence elements modulate transcription efficiency and competition strength of eucaryotic 5 S rRNA and tRNA genes transcribed by RNA polymerase III. We report on the chromatographic separation and functional characterization of at least two components involved in this process: one has a DNA binding activity and interacts with the immediate upstream region of Xenopus tRNA and 5 S rRNA genes, and a second component, which by itself does not interact with the upstream region of these genes, is required together with the DNA binding activity for transcription stimulation in vitro. PMID- 2332438 TI - Generation from a single gene of two mRNAs that encode the mitochondrial and peroxisomal serine:pyruvate aminotransferase of rat liver. AB - In rat liver there are two types of serine:pyruvate aminotransferase (SPT) whose natures are indistinguishable but whose subcellular localization are different. One is a mitochondrial enzyme (SPTm) and the other a peroxisomal enzyme (SPTp). We compared, in this study, the structure of mRNAs encoding SPTm and SPTp by comparison of the sizes after removal of poly(A) tail by ribonuclease H and by means of RNA blot analysis and S1 nuclease protection assay. No differences were detected between these two mRNAs other than that about 100 nucleotides of the 5' terminal sequence of SPTm mRNA are lacking in SPTp mRNA, and the length of the poly(A) tail is different. Southern blot analysis of rat genomic DNA showed that the SPT gene is single. Primer extension and S1 nuclease mapping analyses, using a DNA fragment of a genomic clone, revealed that the SPTm and SPTp mRNAs are transcribed from different initiation sites, about 70 nucleotides apart, in the same exon, exon 1. Ribonuclease protection assay performed with RNA hybridization probe corresponding to 5'-terminal portion of SPTm mRNA also showed that the 5' terminal sequence of SPTp mRNA is about 70 nucleotides shorter than that of hormone-responsive SPTm mRNA. These results indicate that the different organelle distribution of SPTm and SPTp, the products of the same SPT gene, arises from transcription from different initiation sites, conferring N-terminal extension peptide, the mitochondrial targeting signal, only on the translation product of SPTm mRNA. PMID- 2332439 TI - Immunological quantitation and immunohistochemical localization of leukotriene A4 hydrolase in guinea pig tissues. AB - We prepared a highly specific polyclonal antibody against leukotriene (LT) A4 hydrolase using a recombinant human enzyme. Using this antibody, we quantified LTA4 hydrolase protein content in the cytosols of guinea pig tissues. The enzyme protein content correlated well with the enzyme activity with a correlation coefficient of 0.87. However, the enzyme activity per mg of the enzyme in the cytosols was low, particularly in the liver and adrenal gland, compared with the specific activity of the purified enzyme. These observations suggest the presence of inhibitory substances and/or inactive enzymes in the cytosols of these tissues. To determine the cellular localization of LTA4 hydrolase in tissues other than blood cells, we carried out immunohistochemical examinations of guinea pig tissues. We identified epithelial cells in the tracheobronchial system and gastrointestinal tract, smooth muscle cells in the bronchi and aorta, vascular endothelial cells, and the intestinal plexus as novel cellular sources of the enzyme in the parenchyme of the tissue. Thus, LTA4 hydrolase was widely distributed in various types of parenchymal cells in the tissues, and this observation warrants further investigations on the biological activities of LTB4 in these cells and tissues. PMID- 2332440 TI - Expression of the mammalian mitochondrial genome. Role for membrane potential in the production of mature translation products. AB - Protein synthesis was investigated in isolated mitochondria under conditions which either inhibited electron transport or uncoupled oxidative phosphorylation. In a medium containing an exogenous source of ATP and oligomycin, an inhibitor of the ATP synthase complex, incorporation of [35S]methionine into proteins is stimulated in the presence of inhibitors of the electron transport chain; substituting uncouplers of oxidative phosphorylation for the latter leads, in contrast, to a decrease in the rate of incorporation of the labeled amino acid into mitochondrial translation products. Studies on the metabolic stability of mitochondrial translation products revealed that "mature" polypeptides made in isolated mitochondria are stable as indicated by the absence of degradation during a 50 min "chase" period. Under conditions which reduce or dissipate the membrane potential, 50-60% of the newly made polypeptides (pulse) are degraded within 50 min. The kinetics of the degradation process for individual mitochondrial gene products reveal that the largest proportion of polypeptides degraded to an acid-soluble form during the chase period are abnormal proteins, likely the result of premature chain termination. Emerging as a common denominator in these studies is a role for a transmembrane potential across the inner membrane in the production of mature "stable" mitochondrial gene products. PMID- 2332441 TI - Two human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2, are encoded by genes localized to chromosome 13q34 and chromosome Xq24-25, respectively. AB - We have isolated previously cDNAs encoding two related human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2 (Fukuda, M., Viitala, J., Matteson, J., and Carlsson, S.R. (1988) J. Biol. Chem. 263, 18920-18928). In the present study, we have determined the chromosomal localization of genes for h-lamp-1 and h-lamp-2. By using the method of in situ hybridization, we have localized the gene for h lamp-1 to chromosome 13q34 and its related gene to chromosome 12p133. The hybridization of h-lamp-1 cDNA to chromosome 12p133 was observed even when probes representing different portions of h-lamp-1 cDNA were used. On ther other hand, the gene for h-lamp-2 were localized to Xq24-25 but no cross-hybridization to chromosome 12p133 was observed even though h-lamp-1 and h-lamp-2 are highly related. These results clearly indicate that human lamp-1 and lamp-2 are coded by separate genes on different chromosomes. The present results support our hypothesis that lamp-1 and lamp-2 diverged early in evolution and they have distinct functions which emerged as soon as eukaryotic cells acquired lysosomes as subcellular compartments. PMID- 2332442 TI - Transcription initiated by RNA polymerase II and purified transcription factors from liver. Cooperative action of transcription factors tau and epsilon in initial complex formation. AB - Synthesis of accurately initiated transcripts has been reconstituted with RNA polymerase II and a set of five transcription factors purified from rat liver. In addition to three previously identified factors alpha, beta gamma, and delta (Conaway, R. C., and Conaway, J. W. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 7356-7360), transcription in the reconstituted liver system requires two novel factors designated tau and epsilon. These five transcription factors comprise two functional classes: (i) promoter recognition factors (tau and epsilon), which interact with template DNA to facilitate formation of a stable initial complex that is subsequently recognized and bound by RNA polymerase II, and (ii) RNA chain initiation factors (alpha, beta gamma, and delta), which do not participate in formation of the initial complex, but which are essential for transcription initiation. PMID- 2332443 TI - Characterization of fetal porcine bone sialoproteins, secreted phosphoprotein I (SPPI, osteopontin), bone sialoprotein, and a 23-kDa glycoprotein. Demonstration that the 23-kDa glycoprotein is derived from the carboxyl terminus of SPPI. AB - Demineralizing extracts of porcine bone contain two large 66-80-kDa sialoproteins and smaller 20- and 23-kDa glycoproteins with similar chemical properties. Each protein was characterized following extraction from fetal calvariae and purification under dissociative conditions using Sepharose CL-6B, followed by fast protein liquid chromatography fractionation on hydroxyapatite and Mono Q resins. Unlike the large sialoproteins, the 20- and 23-kDa glycoproteins did not contain sialic acid. Nevertheless, affinity-purified antibodies raised against the 23-kDa protein recognized both the 20-kDa protein and a 67-kDa sialoprotein on immunoblots. These antibodies also immunoprecipitated a 60-kDa [35S]methionine labeled protein produced by cell-free synthesis of calvarial bone mRNA, indicating that the smaller proteins were derived from the 67-kDa protein. The two sialoproteins were shown by primary sequence analysis to be secreted phosphoprotein I (SPPI, osteopontin, bone sialoprotein I) and bone sialoprotein (BSP, bone sialoprotein II). The SPPI was also characterized by its susceptibility to thrombin which produced a 23-kDa fragment, similar to the glycoprotein isolated, and a 30-kDa fragment. Amino-terminal sequence analysis of the 23- and 20-kDa proteins revealed that these proteins were derived from the carboxyl-terminal half of the SPPI molecule, the proteins showing 58% identity with human and rat, and 50% identity with mouse, SPPI sequences. Both the 23- and 20-kDa proteins appeared to be generated by the activity of an endogenous trypsin like protease that cleaves at Arg-Ser (residues 155-156) and Lys-Ala (residues 182-183) bonds. Radiolabeling studies performed in vitro showed that the 23-kDa fragment was detectable in mineralized tissue within 4 h. The fragment was phosphorylated but, unlike SPPI, was not sulfated. The rapid generation of the 23 kDa glycoprotein and its presence in different bone tissues at different developmental stages indicate that the fragmentation of SPPI is important in bone formation and remodeling. PMID- 2332444 TI - The steroid-dependent regulatory element in the ovalbumin gene does not function as a typical steroid response element. AB - Transcription of the chicken ovalbumin gene is induced both in vivo and in vitro by four classes of steroid hormones. Recent experiments identified a steroid dependent regulatory element (SDRE) in the 5'-flanking region of the ovalbumin gene between -900 and -521. To characterize the regulatory properties of the SDRE more precisely, additional mutations were created in this region, and fusion genes prepared by linking the ovalbumin 5'-flanking region and promoter to the chloramphenicol acetyltransferase structural gene. When the ovalbumin chloramphenicol acetyltransferase fusion genes were transfected into steroid responsive primary oviduct cells, mutants lacking sequences between -900 and -732 were no longer responsive to estrogen, corticosterone, progesterone, or dihydrotestosterone. The SDRE did not confer steroid-dependent expression on the heterologous thymidine kinase promoter by itself but did in conjunction with the negative regulatory element identified between -350 and -100. This suggests that the two elements act as a single functional entity and that the SDRE is not behaving as a typical steroid response element. Gel shift analyses revealed that two SDRE.protein complexes were formed when nuclear protein extracts were derived from estrogen-treated chicken oviduct but that only one complex was formed with extracts from estrogen-withdrawn oviduct or from other tissues. Neither an estrogen response element oligomer nor a glucocorticoid/progesterone response element oligomer competed for either of the DNA.protein complexes. Partially purified progesterone receptor also did not bind to the SDRE. These data indicate that induction of the ovalbumin gene by steroid hormones requires complex interactions involving both the SDRE and the negative regulatory element. PMID- 2332445 TI - Interactions of tubulin with guanylyl-(beta-gamma-methylene)diphosphonate. Formation and assembly of a stoichiometric complex. AB - Complete replacement of the nucleotide on the exchangeable binding site of purified calf brain tubulin by the non-hydrolyzable GTP-analogue guanylyl (beta,gamma-methylene)diphosphonate (GMPPCP) has been achieved by treatment of tubulin-GDP with phosphodiesterase-free alkaline phosphatase. GMPPCP binds to tubulin with a low affinity relative to GTP or GDP. Binding of the analogue is linked to magnesium ion concentration and, like the binding of other guanine nucleotides, is promoted by high concentrations of glycerol. The complex of pure tubulin and GMPPCP readily assembles at 37 degrees C into microtubules or curled ribbons of protofilaments, depending on buffer composition. Assemblies are cold reversible at 0-2 degrees C, and multiple reversible assemblies can be observed during repeated heating/cooling cycles. PMID- 2332446 TI - Primary structure of rat ceruloplasmin and analysis of tissue-specific gene expression during development. AB - cDNA clones corresponding to rat ceruloplasmin were isolated from newborn rat lung and liver cDNA libraries and the nucleotide sequence was obtained. The derived amino acid sequence of rat ceruloplasmin is 93% homologous to the corresponding human sequence and contains a 19-amino acid leader peptide plus 1040 amino acids of mature protein. Southern blot analysis indicates that the ceruloplasmin gene exists as a single copy in the rat haploid genome. Using these cDNA clones in RNA blot analysis, a single 3.7-kilobase ceruloplasmin-specific transcript is detected in fetal rat liver and lung by day 15 of gestation. During fetal development the abundance of this transcript increases selectively in these two tissues and at birth is 60% of that found in the adult liver. Postnatally the temporal pattern of ceruloplasmin gene expression in lung and liver differs. Within the first 3 weeks postpartum ceruloplasmin mRNA content decreases in lung to undetectable levels, while that in the liver reaches adult levels. Primer extension reveals a single identical start site of ceruloplasmin gene transcription in lung and liver and biosynthetic studies indicate that each tissue synthesizes a ceruloplasmin protein which is qualitatively similar to that synthesized by adult liver. Ceruloplasmin mRNA is also detected in human fetal lung explant and a human lung adenocarcinoma cell line suggesting that a similar pattern of expression occurs in the developing human lung. These data indicate that lung is the predominant extrahepatic site of ceruloplasmin gene expression during fetal development and suggest that this protein may play a previously unappreciated role in lung development or pulmonary antioxidant defense. PMID- 2332447 TI - Factors that promote progressive development of the osteoblast phenotype in cultured fetal rat calvaria cells. AB - Rat calvaria osteoblasts derived from 21-day-old fetal rat pups undergo a temporal expression of markers of the osteoblast phenotype during a 5 week culture period. Alkaline phosphatase and osteocalcin are sequentially expressed in relation to collagen accumulation and mineralization. This pattern of expression of these osteoblast parameters in cultured rat osteoblasts (ROB) is analogous to that seen in vivo in developing fetal rat calvaria tissue (Yoon et. al: Biochem. Biophis. Res. Commun. 148:1129, 1987) and is similar to that observed in cultures of subcultivated 16-day-old embryonic chick calvaria-derived osteoblasts (COB) (Gerstenfeld, et.al: Dev. Biol. 122:46, 1987). While the cellular organization of subcultivated COB and primary ROB cultures are somewhat different, the temporal expression of the parameters remains. Both the rat and chick culture systems support formation of matrix mineralization even in the absence of beta-glycerol-phosphate. A systematic examination of factors which constitute conditions supporting complete expression of the osteoblast phenotype in ROB cultures indicate requirements for specific serum lots, ascorbic acid and the ordered deposition of mineral in the extracellular matrix. The present studies suggest that formation of a collagenous matrix, dependent on ascorbic acid, is requisite for expression of the osteoblast phenotype. In ROB cultures, expression of osteocalcin synthesis occurs subsequent to initiation of alkaline phosphatase activity and accompanies the formation of mineralized nodules. Thus, extracellular matrix mineralization (deposition of hydroxyapatite) is required for complete development of the osteoblast phenotype, as reflected by a 200-fold increase in osteocalcin synthesis. These data show the temporal expression of the various osteoblast parameters during the formation and mineralization of an extracellular matrix can provide markers reflective of various stages of osteoblast differentiation/maturation in vitro. PMID- 2332448 TI - Immortal phenotype of the HeLa variant D98 is recessive in hybrids formed with normal human fibroblasts. AB - Normal human cells such as human diploid fibroblasts (HDF) have a finite proliferative lifespan in culture. Previous studies have shown that the limited lifespan phenotype is dominant in cell hybrids formed by fusion of HDF to at least 23 different kinds of immortal human cells. However, two independent studies reported that hybrid clones formed by the fusion of HDF to the HeLa variant D98 had unlimited division potential. Those results were potentially very important because they implied that a) there is a dominant mechanism for immortalization of human cells in addition to the well-documented recessive mechanism, and b) a dominant mechanism would lend itself to identification of the immortalizing gene. Consequently, we carried out more detailed studies of the behavior of D98 cells in hybrids. Our results indicate that the majority of D98 x HDF hybrid clones exhibit a clear-cut finite proliferative lifespan phenotype. In addition, these hybrid cell populations often give rise to an immortal focus of cells that can be seen to take over the population of mortal cells at the end of their lifespan. This phenomenon reconciles our data with the previous reports of immortal D98 x HDF hybrid clones and leads us to conclude that D98 cells do not express a dominant immortalizing gene. PMID- 2332449 TI - Transcriptional regulation of DF3 gene expression in human MCF-7 breast carcinoma cells. AB - The DF3 gene codes for a high molecular weight human breast tumor-associated glycoprotein. The detection of this antigen in human milk has also suggested that its expression represents a differentiated function of mammary epithelium. The present studies have examined the regulation of DF3 gene expression in human MCF 7 breast carcinoma cells. These cells express two DF3 transcripts of 4.5 and 7.0 kb. Treatment of MCF-7 cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) was associated with increases in levels of both DF3 mRNAs. When nuclear run-on assays were used, DF3 gene transcription was at low to undetectable levels in untreated MCF-7 cells and was increased after TPA exposure. TPA-induced increases in DF3 mRNA levels were also inhibited by actinomycin D (ACT). MCF-7 cells exposed to ACT further demonstrated that the half-lives of the 4.5 and 7.0 kb transcripts are 26 and 11 h, respectively. The results also demonstrate that the protein synthesis inhibitor, cycloheximide (CHX), increases DF3 mRNA levels in MCF-7 cells. These effects of CHX were sensitive to actinomycin D and not associated with stabilization of the DF3 transcripts. Taken together, these findings indicate that DF3 gene expression is controlled at a transcriptional level in TPA and CHX-treated MCF-7 cells. PMID- 2332450 TI - Length-dependence of isometric twitch tension potentiation and myosin phosphorylation in mouse skeletal muscle. AB - The effect of changes in muscle length on post-tetanic isometric twitch tension potentiation and myosin P-light chain phosphorylation was studied at 23 degrees C in the mouse extensor digitorum longus muscle. The length-tension relationship was determined for the same muscles after a 30 min period of quiescence and between 30 s and 3 min after a 1.5 s tetanus at L0. Isometric twitch tension is increased at all muscle lengths after the tetanus; however, the fractional increase in twitch tension rises from 0.2 at L0 to a maximum of 0.3 at 1.2 L0. The fractional increase in twitch tension measured at any fixed muscle length is constant between 30 s and 3 min post-tetanus. P-light chain phosphorylation remains constant between 30 s and 3 min post-tetanus followed by a slow decline to basal values. Under fixed length conditions, there is linear relationship between the relative magnitude of the twitch tension and the extent of P-light chain phosphorylation. Net myosin phosphorylation measured after a 1.5 s tetanus at 1.23 L0 is 35% less than that obtained under the same conditions at L0. Thus, contraction-induced phosphorylation of P-light chain decreases with increased muscle length and post-tetanic potentiation at a constant level of P-light chain phosphorylation increases with increasing muscle length. These observations may be consistent with alterations in the sarcoplasmic Ca2+ ion transient as the muscle is lengthened. PMID- 2332451 TI - Clonal segregation of multiple and overlapping matrix adhesive responses in dorsal root neuronal derivative cells. AB - Clones of F11 hybrid (neuroblastoma X dorsal root neuron) cells have been tested for adherence and neurite outgrowth on three different substrata on which the parental cells display some competence--plasma fibronectin (pFN) with its multiple receptors, cholera toxin subunit B(CTB) as a model ganglioside GM1 binding substratum, and platelet factor-4 (PF4) as a model proteoglycan-binding substratum. This paradigm tests for independently segregating and overlapping mechanisms of neuritogenesis via transmembrane processes in pluripotent hybrid cells based on random loss of chromosomes contributed by the parent neural cells. For the nine clones tested, attachment was significantly lower on CTB but much higher on PF4 for all clones when compared to their attachment on pFN. Supplementation of cells with GM1 stimulated attachment of only two clones (on all three substrata). Neurite outgrowth was observed in a substratum-specific pattern and varied from 0 to greater than 60% on pFN; on CTB and PF4 substrata, the patterns were similar to each other but differed markedly from the pattern on pFN. In contrast, PF4- and CTB-directed neurites differed morphologically from each other while sharing some characteristics with neurites on pFN. Supplementation with GM1 or GT1b, but not GD1a, was inhibitory for neurite outgrowth in certain clones. Cycloheximide pretreatment distinguished several classes of clones based on inhibition of neuritogenesis. While most clones on pFN were unaffected, all clones on CTB and PF4 displayed significant and comparable degrees of inhibition, suggesting the sharing of some protein intermediate(s) on these substrata. Exposure to cycloheximide only during the active period of neuritogenesis generated higher percentages and longer neurites for all clones, indicating a widely-used negative regulation mechanism. Based on substratum type and cycloheximide protocols, these data have resolved six or more different transmembrane signalling processes for generating different classes of neurites. Some mechanisms have been segregated into individual clones while others overlap in other clones, providing cell systems for biochemical and molecular biological dissection of these processes. PMID- 2332452 TI - Low temperature blocks exit of pro-opiomelanocortin from the endoplasmic reticulum but not subsequent delivery to the site of prohormone processing. AB - The effect of reduced temperature on the delivery of the prohormone pro opiomelanocortin (POMC) to the site of prohormone processing was investigated in the mouse anterior pituitary cell line AtT20. At 20 degrees C processing was substantially inhibited and was almost completely arrested at 18 degrees C. Earlier studies with membrane glycoproteins indicated that at these temperatures protein movement was blocked at the level of exit from the Golgi apparatus. In contrast it was found here that the inhibition of processing at reduced temperature was due to the retention of POMC in the endoplasmic reticulum. When POMC was allowed to progress to the Golgi before temperature was reduced, subsequent processing was only slightly retarded by incubation at 18 degrees C. This indicates either that Golgi exit is not inhibited at this temperature, or that the processing apparatus exists in the Golgi. A surprising incidental result was that when held in the endoplasmic reticulum at low temperature POMC is apparently subject to post-translational N-linked glycosylation. PMID- 2332453 TI - DNA synthesis inhibition and reduced functional differentiation of midpregnant mouse mammary epithelia on collagen gels. AB - Mammary epithelial cells were examined for a link between DNA synthesis and subsequent synthesis and secretion of casein. Cells isolated from mice midway through pregnancy and cultured on collagen gels spread to form monolayers (spreading phase). Release of monolayer/gels to float in surrounding culture medium induces synthesis and secretion of casein (secretory phase). DNA synthesis was blocked during the spreading phase with cytosine arabinofuranoside (ARA C). Culture medium was assayed for casein by direct quantification of protein from SDS-PAGE fluorographs, and by immunoblotting. When induced to become secretory, cells exposed to ARA C during the spreading phase showed a marked reduction of secretion of casein as compared to control cultures (72% reduction). In contrast, cells exposed to ARA C during the secretory phase (after monolayer formation was complete) showed no significant reduction in secretion of casein. Measurement of intracellular casein in secretory phase cells showed that reduced secretion of casein by cultures blocked during the spreading phase occurs as a consequence of reduced levels of casein synthesized, and not because of an inability to secrete intracellular accumulations. The inhibitor effect was specific; there was no significant reduction in levels of total intracellular protein synthesis, and neither cell spreading nor monolayer formation was impaired by treatments. These data support the notion that DNA synthesis is a prerequisite to functional differentiation of midpregnant mouse mammary epithelia maintained on floating collagen gels. PMID- 2332454 TI - p52 induction by cytochalasin D in rat kidney fibroblasts: homologies between p52 and plasminogen activator inhibitor type-1. AB - Normal rat kidney (NRK) fibroblasts respond to the cell shape-modulating chemical agent cytochalasin D (CD) with augmented synthesis of the 52-kDa substrate associated protein p52. p52 is a complex glycoprotein, existing as 12 different isoforms, which include a 43-kDa "core" protein (p43), four 50-kDa species (p50 0,1,2,3), and at least seven distinct pI variants of the mature 52-kDa protein. A threshold of 2-4 microM CD was found to be necessary to augment p52 deposition into both the secreted protein- and saponin-resistant cytomatrix (SAP) fractions of NRK cells. This concentration of CD was also necessary to initiate significant cell rounding. Augmented p52 production in CD-treated NRK (NRK/CD) cells provided a means to assess the identity of this protein. p52 was found to be identical to rat plasminogen activator inhibitor type-1 (rPAI-1) and to PAI-1-like proteins of other species by comparative immunoprecipitation, 2-D electrophoretic profile, V8 protease digest mapping, and subcellular fractionation criteria. Quantitation of rPAI-1 cytoplasmic mRNA abundance, using the rPAI-1 cDNA probe pSS1-3, revealed an induction of rPAI-1 mRNA in NRK/CD cells which paralleled the increased protein production. CD-augmented p52(rPAI-1) synthesis and SAP deposition was blocked by actinomycin D, implicating a need for RNA synthesis during the period of CD exposure to effect induction. Augmentation of p52 expression in NRK/CD fibroblasts, thus, appears to involve both cell shape-associated metabolic processes and concomitant RNA synthesis. PMID- 2332455 TI - Regulation of hexose transport in L8 myocytes by glucose: possible sites of interaction. AB - Previous work demonstrated that glucose controls its own transport rate in rat skeletal muscle: exposure to high glucose levels down-regulates muscle hexose transport, while glucose withdrawal results in elevated transport rates (J. Biol. Chem. 261:16827-16833, 1986). The present study investigates the mechanism of this autoregulatory system. Preincubation of L8 myocytes at 16 mM glucose reduced subsequent 2-deoxy-D-glucose (dGlc) uptake by 40% within 3 h. Cycloheximide (1 microM) mimicked the action of glucose; the effects of glucose and cycloheximide were not additive. At 50 microM, cycloheximide prevented the modulations of glucose transport induced by exposure of muscle cells to high or low glucose concentrations. Inhibition of glycosylation with tunicamycin A1 reduced the basal dGlc uptake, but did not prevent its up-regulation following glucose withdrawal. Inhibition of RNA synthesis by actinomycin D prevented the down-regulatory effect of glucose. These results indicate that continuous protein synthesis and protein glycosylation are required for the maintenance of the steady-state dGlc uptake. We suggest that glucose exerts its autoregulatory effect on hexose transport by modifying the incorporation of active glucose transporters into the plasma membrane rather than changing their rate of degradation. It is hypothesized that this effect is mediated by a non-glycosylated protein involved in the translocation or activation of glucose transporters. PMID- 2332456 TI - Adenosine metabolism in kidney slices under normoxic conditions. AB - The effect of adenosine in rat kidney under normoxic conditions has been studied. It is demonstrated that adenosine modulates cell nucleotide levels. HPLC analysis of the purine compounds inside the cell indicates that adenosine improves the ATP/ADP ratio, whereas it diminishes the adenine content. This behaviour is not due to mediation by specific receptors, as agonists at P1 purinoceptors did not have any effect. Further evidence using inosine as well as dipyridamole and deoxycoformycin indicates that all effects are dependent on the previous uptake of adenosine. The origin of free adenine in the kidney has been investigated, and it appears to come from the phosphorolysis of 5'-methylthio-adenosine. This report is the first to describe the activity of methylthioadenosine phosphorylase (E.C. 2.4.2.28) in the kidney. It is concluded that 1) extracellular adenosine improves guinea pig renal function by increasing the ATP level and the ATP/ADP ratio; and 2) there exists a functional pathway in the kidney that produces adenine and AMP coming from methionine and ATP. This latter pathway probably produces spermine and spermidine, which are likely to be important for renal function. PMID- 2332457 TI - Use of chlortetracycline fluorescence for the detection of Ca storing intracellular vesicles in normal human erythrocytes. AB - The uptake of chlortetracycline (CTC) and the nature of the fluorescence of CTC was studied in intact human erythrocytes from apparently healthy donors. The uptake of CTC at 22 degrees C proceeded with a t1/2 of about 3 min, and after 15 min a stable equilibrium was achieved with an intracellular accumulation by a factor of 5-6 relative to the medium concentration. The accumulation did not change in the range of CTC concentrations tested (20-500 microM). The Ca specificity of the CTC fluorescence spectrum was confirmed by Ca depletion of red cells using A23187 in the presence of EGTA and 0.2 mM Mg. This procedure decreased the total intracellular calcium content by about 70% and reduced the fluorescence intensity to one-fourth. Fluorescence microscopy of red cells incubated with 100 microM CTC at 22 degrees C showed that the fluorescence originated mainly from the red cell membrane. In addition, in about 15% of erythrocytes one or more fluorescent dots (diameter greater than 0.2 less than 1 microns) were detected. The fluorescence of the dots and membranes was related to calcium, as evidenced by the reduction of their intensity in Ca depleted cells. The number of erythrocytes with fluorescent dots and the frequency of the dots per cell was largely unaffected by lowering the incubation temperature to 0 degrees C, indicating that the dots most probably do not represent endocytotic artifacts induced by CTC. The number of dots was increased in erythrocytes preincubated with primaquine, demonstrating that CTC fluorescence can be applied to monitor the appearance of intracellular Ca storing vesicles. It is concluded that in (at least) 15% of erythrocytes obtained from apparently healthy donors intracellular vesicles containing Ca can be detected by CTC fluorescence microscopy. PMID- 2332458 TI - Small intestinal differentiation in human colon carcinoma HT29 cells has distinct effects on the lateral diffusion of lipids (ganglioside GM1) and proteins (HLA class 1, HLA class 2, and neoplastic epithelial antigens) in the apical cell membrane. AB - We have studied the effect of maturation to small intestinal-like epithelial cells of the human colonic carcinoma cell line HT29 on the lateral mobility of different representative membrane components (lipid, proteins), as assessed with fluorescence recovery after photobleaching (FRAP). Maturation was induced in vitro in the HT29 cells by replacing glucose (Glu) with galactose (Gal) in the growth medium (DMEM) during a 21-day period. Scanning electron microscopy revealed an increased number of microvilli in the apical cell membrane, and enzyme analyses (alkaline phosphatase, aminopeptidase) in combination with aqueous countercurrent distribution, indicated that maturation was induced with DMEM-Gal. In comparison to control cells grown in DMEM-Glu medium, the more small intestinal-like cells grown in DMEM-Gal displayed no alteration of the lateral mobility of either cholera toxin (B subunit)-labelled ganglioside GM1 (diffusion coefficient, D [x 10(8)] = 0.8-0.9 cm2s-1; mobile fraction, R = 50-60%) or antibody-stained Class 2 histocompatibility (HLA-DR) antigen (D [x 10(9)] = 2 cm2s-1; R = 60-70%). However, antibody-labelled beta 2-microglobulin of HLA Class 1 antigen displayed increased mobility in HT29-Gal cells; D was x 1.4 and R x 1.8 larger in the HT29-Gal cells. By contrast, the mobility of a neoplastic antigen was reduced; D and R were x0.60 and x0.69 of the values seen in HT29-Glu cells. It is thus concluded that DMEM-Gal-induced differentiation in confluent HT29 cells is accompanied by specific rather than general effects on the lateral mobility of different membrane components. PMID- 2332459 TI - Quantification of protein transcytosis in the human colon carcinoma cell line CaCo-2. AB - The transepithelial absorption of food-type proteins has been shown to proceed by endocytosis along two functional pathways: a minor direct pathway allowing transport of intact protein and a major lysosomal degradative pathway. The human colon carcinoma cell line CaCo-2 grown on Millipore filters was used here further to characterize these pathways by measuring HRP transport across the cell monolayer in Ussing chambers. In the apical-basal direction, this transport mainly occurred along the degradative pathway and was inhibited at 4 degrees C (7.41 +/- 1.26 pmoles/h.cm2 vs. 27.40 +/- 8.91 at 37 degrees C). The amount conveyed via the direct pathway was very small (0.89 +/- 0.35 pmoles/h.cm2) and did not diminish at 4 degrees C (1.43 +/- 0.59 pmoles/h.cm2). In the basal-apical direction, HRP transport along the degradative pathway at 37 degrees C was similar to the apical-basal value and was inhibited at 4 degrees C (16.40 +/- 4.05 vs. 2.72 +/- 2.52 pmoles/h.cm2), but along the direct pathway, it was eight times the apical-basal value (8.36 +/- 3.11 pmoles/h.cm2) and was inhibited at 4 degrees C (2.43 +/- 0.78 pmoles/h.cm2). Intact HRP fluxes were not correlated with the electrical resistance of the filters, indicating transport via a transcellular route. Monensin at 10(-5) M did not affect direct or degradative transport in the apical-to-basal direction. These results suggest that in CaCo-2 cells HRP undergoes bidirectional transcytosis by a fluid-phase mechanism, but the extent of degradation during that transport varies according to the membrane (apical or basal) where it is presented. PMID- 2332460 TI - Adduct formation identification between phenyl glycidyl ether and 2' deoxyadenosine and thymidine by chromatography, mass spectrometry and nuclear magnetic resonance spectroscopy. AB - Thymidine and 2'-deoxyadenosine were reacted with phenyl glycidyl ether in order to study the formation of the corresponding 2'-deoxynucleoside adducts. Separation methods were elaborated using either reversed-phase high-performance liquid chromatography with photodiode-array detection, or centrifugal circular thin-layer chromatography. The adducts were isolated on a preparative scale and were fully characterized by UV spectroscopy, desorption chemical ionization and fast atom bombardment mass spectrometry and 270- and 360-MHz 1H NMR spectrometry. For thymidine the main adduct was characterized as N-3-(2-hydroxy-3 phenoxypropyl)thymidine. With 2'-deoxyadenosine, predominantly N-1-(2-hydroxy-3 phenoxypropyl)-2'-deoxyadenosine was formed. With longer reaction times, the formation of a minor amount of dialkylated 2'-deoxyadenosine was observed. These nucleoside adducts will be used as marker compounds for studies of DNA adduct formation. PMID- 2332461 TI - Surface affinity chromatographic separation of blood cells. VII. Relationship between capacity factors of human peripheral blood cells and the rate of penetration of liquids into xerogel column packings. AB - Eleven kinds of column packing gels which bonded poly(ethylene glycol) (PEG) to Sepharose 6B (PEG-C10-Sepharose) were prepared. Human peripheral blood cells were chromatographed on these gel columns by eluting with 0.09 M phosphate-buffered 2% (w/w) dextran T40 solution at the pH of the respective isoelectric points of the blood cells. The rate of penetration of water or the mobile phases into the PEG C10-Sepharose xerogels as a measure of the hydrophobicity of the gels depended on both the oxyethylene residue content and the number of oxyethylene units of the packing gels. The capacity factors of granulocytes and lymphocytes were increased on the columns packed with gels having a slower rate of penetration of the liquids into the xerogels. PMID- 2332463 TI - Heat stability of protective antigen of Leptospira interrogans serovar lai. AB - Protective antigen (PAg; glycolipid antigen; molecular size, 23 to 30 kilodaltons), the serogroup-specific antigen partially purified from leptospiral cells, is one of the most important protective antigens. The heat stability of PAg was compared with that of whole-cell (WC) antigen by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, protective activity, opsonin-inducing activity, agglutinating antibody-inducing activity, and an inhibition test in an enzyme-linked immunosorbent assay. A band of 23 to 30 kilodaltons of PAg, which was seen in untreated PAg and WC, shifted to a position with a molecular size of ca. 20 kilodaltons after heat treatment of PAg at 80 degrees C for 30 min and WC at 100 degrees C for 30 min. In the enzyme-linked immunosorbent assay inhibition test with monoclonal antibody LW2 and a sonicated antigen of WC, the inhibition rate of PAg and WC to sonicated WC was reduced by heat treatment at 80 degrees C for 30 min and at 100 degrees C for 30 min, respectively. Agglutinating antibody-inducing activities and opsonin-inducing activities of PAg and WC in mice were reduced by heat treatment under the same conditions; these activities were assayed by a microscopic agglutination test and by chemical luminescence response in serum from immunized mice, respectively. Protective activity of heated PAg and heated WC in cyclophosphamide-pretreated mice agreed with the results of immunogenicity in mice. These results indicate that the Leptospira PAg is one of the important protective antigens and is altered by heat treatment at 80 degrees C. Furthermore, the immunogenicity and antigenicity of the PAg present in WC are more stable than that of the extracted PAg, and the coexistence of other cellular components with PAg might protect and stabilize PAg from the heat treatment. PMID- 2332462 TI - Comparisons of Pasteurella multocida lipopolysaccharides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine relationship between group B and E hemorrhagic septicemia strains and serologically related group A strains. AB - Lipopolysaccharides (LPSs) purified from 16 reference somatic serotypes of Pasteurella multocida were examined and compared by discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Resolution of LPS patterns in a gel was optimum when sample wells were cast separately from the stacking gel and the running gel consisted of 15% T (total monomer) polyacrylamide and 4 M deionized urea. Band patterns of P. multocida LPSs in a gel differed from control Salmonella minnesota wild-type and core mutant LPSs. Although the band patterns and mobilities of LPSs from some P. multocida reference serotypes were similar, none were identical. Evidence for O antigens similar to those produced by enterobacteria was not observed. Proteinase K digestion of whole P. multocida cells resulted in LPS band patterns similar to those of purified LPS. The presence or absence of a capsule on a strain had no major influence on band patterns in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Comparisons of LPS patterns of group B and E hemorrhagic septicemia strains with those of serologically related group A strains of P. multocida indicated that they were similar. Typing antisera made with purified serotype 2 or 5 LPS reacted with electroblots of all these strains. However, the reactions did not distinguish strains as being serotype 2 or 5. PMID- 2332464 TI - Sequential analysis of staphylococcal colonization of body surfaces of patients undergoing vascular surgery. AB - Slime-producing coagulase-negative staphylococci are pathogens in vascular surgery by virtue of their ability to adhere to and persist on prosthetic graft material. Inguinal and abdominal skin sites were cultured in 41 patients upon hospitalization, and slime production and antimicrobial susceptibility were assessed in all recovered staphylococcal isolates. Twenty-one patients eventually underwent lower-extremity revascularization. In the operative population, cultures were also obtained on the day of surgery and fifth postoperative day. All 21 patients received perioperative cefazolin. Of 327 coagulase-negative staphylococci recovered, Staphylococcus epidermidis (47%), S. haemolyticus (21%), and S. hominis (10%) were the predominant isolates. Slime-producing coagulase negative staphylococci were recovered from 17 of 21 patients at admission but only from 8 of 21 patients on day 5 postoperation (P less than 0.05). S. epidermidis isolates demonstrated increasing multiple resistance from admission to 5 days postoperation to methicillin, gentamicin, clindamycin, erythromycin, and trimethoprim-sulfamethoxazole (P less than 0.05). All coagulase-negative staphylococcal isolates were susceptible to ciprofloxacin and vancomycin. Slime producing capability was not associated with increased methicillin resistance for the recovered isolates. The data demonstrate that patients enter the hospital colonized with slime-producing strains of coagulase-negative staphylococci and that during hospitalization the staphylococcal skin burden shifts from a predominately susceptible to a resistant microbial population, which may enhance the importance of slime production as a risk factor in lower-extremity revascularization. PMID- 2332465 TI - Phenotypic variation of Staphylococcus epidermidis in infection of transvenous endocardial pacemaker electrodes. AB - Coagulase-negative staphylococci isolated from a patient with a pacemaker electrode infection were extensively evaluated by phenotypic and genotypic characterization. Findings from this evaluation were striking because different colony morphologic subtypes were recovered from blood and resected pacemaker electrodes. Staphylococci from each colony subtype (LBL, LBV, LBP, LBS) were identified as slime-producing strains of Staphylococcus epidermidis sensu stricto. Direct plating of isolates from a restricted electrode revealed a mixture of colony phenotypes when examined on a high-salt, low-glucose medium, Memphis agar. Bacteriophage typing employing 17 different phages and plasmid profile analysis were largely unsuccessful in further characterizing bacterial cells of each of the four colony morphotypes. On the other hand, restriction endonuclease analysis by EcoRI digestion of the chromosomal DNA demonstrated the probable common clonal origin of the four colony phenotypes. PMID- 2332466 TI - Differentiation of clinical isolates of Entamoeba histolytica by using specific DNA probes. AB - Most individuals infected with Entamoeba histolytica are reported to be clinically asymptomatic. On the basis of the electrophoretic migration of hexokinase and phosphoglucomutase isoenzymes, two groups of E. histolytica isolates have been classified. Those derived from symptomatic cases were found to have fast-migrating hexokinase bands and were labeled pathogenic. The others, isolated from cyst passers, had (in most cases) slow-migrating bands and were called nonpathogenic. Differences between these two groups of E. histolytica were found recently at the DNA level. Two sets of different DNA probes derived from tandemly repeated sequences present in extrachromosomal circular DNA elements in each group of E. histolytica were characterized. Using these probes with procedures for direct hybridization of trophozoites on nylon membranes, we could correctly correlate hexokinase electromobility with the DNA hybridization signal of 81 different isolates of E. histolytica. The advantages of using DNA probes lie in their sensitivity (fewer than 200 trophozoites can be detected) and specificity. The probes hybridized only with amebae from the E. histolytica species and not with other enteric protozoa and can be useful as a diagnostic tool. PMID- 2332467 TI - Biochemical and chemical characterization of pink-pigmented oxidative bacteria. AB - The biochemical and chemical characteristics were determined for 156 clinical isolates of pink-pigmented bacteria that are similar to but distinct from Methylobacterium extorquens (synonymous with Pseudomonas mesophilica). These isolates were gram-negative, nonfermentative, usually nonvacuolated, coccoid rods; all grew at 35 degrees C and were catalase and urease positive; the majority grew on MacConkey agar and were variable for oxidase production and motility. On the basis of oxidation of xylose and mannitol and hydrolysis of esculin, these 156 strains were subdivided into four groups that were designated "pink coccoid" groups I, II, III, and IV. Groups I, II, and III are similar to an unnamed taxon described by Gilardi and Faur in 1984; only strains of group IV hydrolyze esculin. The cellular fatty acid compositions of strains of groups I, II, and III were essentially identical and differed from strains of group IV by the absence of 3-OH-C14:0 and the presence of C19:0 delta and 2-OH-C19:0 delta. The fatty acid composition of group IV strains was most similar to that of M. extorquens but differed by the presence of small amounts of two C17:1 acids, 3-OH C16:0, and 2-OH-C18:1. PMID- 2332468 TI - DNA and protein analyses of tick-derived isolates of Borrelia burgdorferi from California. AB - Nine isolates of Borrelia burgdorferi from ixodid ticks collected in northern California were characterized. Restriction endonuclease analysis, pulsed-field gel electrophoresis, and Western blot (immunoblot) analysis were used in this study. Four isolates were very similar to each other. The others shared some similarities but were classified as having unique genotypes. A strain from an Ixodes neotomae tick displayed the greatest genetic and antigenic diversity when compared to the isolates collected from Ixodes pacificus ticks. A computerized library based on DNA banding patterns of the isolates by restriction enzyme analysis is also reported. This library was created by using a scanning laser densitometer. PMID- 2332469 TI - Implications of antibodies to pyruvylated glucose in healthy populations for mycobacterioses and other infectious diseases. AB - Members of the Mycobacterium avium-Mycobacterium intracellulare (MAI) complex are typeable because each serovar is characterized by its own specific antigenic glycolipid. By means of an enzyme-linked immunosorbent assay, we studied serum specimens obtained from 148 healthy college students for antibodies to these glycopeptidolipids. Ninety-two (61.5%) of the serum specimens were positive to the specific glycolipid antigen from MAI serovar 8. In a study of a pediatric population, antibodies appeared to develop during adolescence. Individuals with overt mycobacterial disease had a significantly lower incidence (tuberculosis patients, 34.5%; leprosy patients, 25%). We found a lower incidence of positive results in a survey of 96 Japanese serum specimens (29.1%), but the results from a survey of sera obtained from Bombay, India, indicated a large degree of reactivity (55.5%). Antibodies to other MAI serovars (serovars 2, 4, and 11) were not found, except antibodies to MAI serovar 21 were seen in the same individuals with antibodies to serovar 8. The dominant epitope of the MAI serovar 8-specific glycopeptidolipid is a terminal pyruvylated 3-O-methylglucose residue [4,6-(1' carboxyethylidene)-3-O-methyl-alpha-D-glucopyranosyl] unit, whereas that of the MAI serovar 21 has the same terminal pyruvylated glucose devoid of the 3-methoxy group. Thus the antibodies appear specific for the pyruvylated glucose. It is unclear whether the high prevalence of antibodies to these epitopes reflects a high incidence of subclinical colonization or infection with certain MAI serovars or whether they are acquired through contact with some other related antigen source. PMID- 2332470 TI - Microculture assay for isolation of human immunodeficiency virus type 1 and for titration of infected peripheral blood mononuclear cells. AB - To define the optimal conditions for human immunodeficiency virus (HIV) detection in microcultures, experiments were conducted with different ratios of patient and donor peripheral blood mononuclear cells (PBMCs). Donor/patient PBMC ratios ranged from 1:1 to 1:125. Optimal results were obtained when 1,500,000 donor cells were cocultured with equal or smaller quantities of patient PBMCs. Thus, virologic endpoints could be achieved by diluting patient cells. Smaller numbers of donor cells, with or without larger numbers of patients cells, resulted in lower rates of HIV isolation. Similarly, the direct stimulation of patient PBMCs with phytohemagglutinin without the addition of normal donor cells lowered the sensitivity of the assay significantly. We suggest that a microculture procedure using a fixed quantity of donor cells with different dilutions of patient cells may be useful for monitoring changing HIV levels during antiviral therapy. PMID- 2332471 TI - Quantitative culture of endocervical Chlamydia trachomatis. AB - We examined the number of Chlamydia trachomatis inclusions produced in the initial passage of cell cultures of endocervical specimens from 1,231 women with positive chlamydial cultures who attended a sexually transmitted diseases clinic. Youth, white race, oral contraceptive use, and concurrent infection by Neisseria gonorrhoeae were associated with high chlamydial inclusion counts. Youth, white race, and oral contraceptive use were independent determinants of a high chlamydial inclusion count in women without concurrent gonorrhea but not in women with gonorrhea. Results of our study suggest that the degree of chlamydial excretion from the infected cervix may be influenced by characteristics of the patient being tested and may affect the ability to detect C. trachomatis in different patient groups. PMID- 2332472 TI - Prevalence of seroreactors to the 104-kilodalton hemolysin of Actinobacillus pleuropneumoniae in swine herds. AB - A rabbit homologous polyclonal antiserum to the 104-kilodalton hemolysin of Actinobacillus pleuropneumoniae serotype 1 strain CM-5 was specifically produced and used in an antigen capture enzyme-linked immunosorbent assay (ELISA) to detect swine serum antibodies to this potentially important virulence factor. Sera from pigs experimentally infected with the most common disease-producing serotypes (serotypes 1, 2, 5, and 7) of A. pleuropneumoniae produced positive results in this ELISA. Of 144 serum samples collected from 10 herds free of pleuropneumonia and 155 serum samples from 11 herds with a history of the disease, 68 (47%) and 148 (95%), respectively, were found positive by the ELISA. In addition, pigs naturally infected with Actinobacillus suis produced antibodies which seroreacted in this ELISA. The results indicated that a high proportion of swine have antibodies seroreactive with the 104-kilodalton hemolysin produced by A. pleuropneumoniae. PMID- 2332473 TI - Simple assay of calcium dependency for virulent plasmid-bearing clones of Yersinia enterocolitica. AB - A simplified procedure to detect the calcium dependency of virulent plasmid bearing strains of Yersinia enterocolitica was developed. A low-calcium, agarose based medium of brain heat infusion with added magnesium effectively differentiated plasmid-bearing and plasmidless isolates. Further, the expression of calcium dependency in plasmid-bearing strains of Y. enterocolitica as measured by the average colony diameter was proportional to the calcium concentration of the assay. PMID- 2332474 TI - Evaluation of enzyme-linked immunoassay systems for detection of human immunodeficiency virus type 1 antibody from filter paper disks impregnated with whole blood. AB - Five commercial enzyme-linked immunoassay systems for the detection of human immunodeficiency virus type 1 antibody from filter paper disks impregnated with whole blood were evaluated for technical and operational performance. All five systems performed adequately in the technical challenges posed, with specificities in excess of 99% for 1,020 specimens. In a serial dilution sensitivity challenge, all of the kits were able to detect specific antibody within one dilution of a Western blot (immunoblot) standard, except for a Du Pont Co. kit, which detected antibody within two dilutions of the standard. The Du Pont assay showed the least variation in control values between test runs and between lots. All of the systems produced acceptable results, but their operational parameters differed significantly. PMID- 2332475 TI - Effect of iron on production of a possible virulence factor by Plesiomonas shigelloides. AB - Plesiomonas shigelloides, when grown in an iron-poor medium (syncase), produces a substances that causes elongation of Chinese hamster ovary (CHO) cells similar to that produced by cholera toxin. When syncase is supplemented with iron, the ability of P. shigelloides (but not of Vibrio cholerae) to produce this elongation of CHO cells is lost. Iron depletion of the growth medium appears to be essential for the CHO cell elongation produced by P. shigelloides but is not essential for the production of toxin by V. cholerae. The possible role of iron regulation of this potential virulence factor warrants further study. PMID- 2332476 TI - Culture confirmation of Campylobacter spp. by latex agglutination. AB - A commercial latex agglutination test [Meritec-Campy (jcl), Meridian Diagnostics, Cincinnati, Ohio] was evaluated for identification of Campylobacter jejuni, C. coli, C. laridis, and other Campylobacter isolates. The test had 100% sensitivity in detecting C. jejuni and C. coli but low sensitivity with C. laridis isolates. C. upsaliensis strains reacted with the test. The test had 100% specificity for 101 non-Campylobacter organisms. PMID- 2332477 TI - Evaluation of the Recombigen HIV-1 Latex Agglutination Test. AB - The Recombigen HIV-1 Latex Agglutination (LA) Test was recently licensed by the U.S. Food and Drug Administration for use as a rapid screening assay for human immunodeficiency virus type 1 (HIV-1) antibodies. However, its performance in various settings and in different populations has not been firmly established. Consequently, we evaluated the test in the Cleveland Clinic Retrovirus Laboratory, a regional reference laboratory for HIV diagnostic testing and a testing laboratory for the Ohio Department of Health Anonymous HIV Testing and Counseling Program. Serum samples from 93 individuals presumed to be at high risk for HIV infection were evaluated. The sera were initially tested for HIV antibodies by enzyme-linked immunosorbent assay (ELISA). All repeatedly reactive sera were subjected to confirmatory Western blot (WB; immunoblot) testing. Of 97 serum specimens tested (5 were from one seroconverter), 44 were repeatedly reactive by ELISA and 53 were nonreactive. Of the reactive serum specimens, 31 were confirmed positive and 12 were indeterminate by WB. All of the sera were coded and then retested by the LA test. Of 53 serum specimens nonreactive by ELISA, 51 were also nonreactive in the LA test. Of the 44 serum specimens reactive by ELISA, 16 were nonreactive by LA; however, 3 of the latter were WB positive. No serum specimen with an ELISA ratio (specimen optical density/cutoff optical density) of less than 2.1 scored reactive in the LA test. The LA test was positive for only two of five consecutive serum specimens from a seroconverter despite the fact that all but the earliest of these were ELISA reactive and WB positive. Although the LA test appears to be an adequate first-line screening test when appropriately used according to the directions of the manufacturer, our data suggest that occasional sera with low levels of reactivity by ELISA may not be readily detected as reactive by the LA test. PMID- 2332478 TI - Biotype-specific probe for Vibrio cholerae serogroup O1. AB - The O1 serogroup of Vibrio cholerae can be divided into two biotypes, El Tor and Classical. Current tests to distinguish between these biotypes are often difficult to interpret. On the basis of the difference in sequence of the hlyA gene in these biotypes, we have developed a simple probe that can easily and reliably differentiate between the two biotypes. PMID- 2332479 TI - Rapid diagnosis of typhoid fever through identification of Salmonella typhi within 18 hours of specimen acquisition by culture of the mononuclear cell platelet fraction of blood. AB - Detection of Salmonella typhi in blood by culture of the mononuclear cell platelet layer was compared with other methods currently used for the diagnosis of typhoid fever. Colonies of S. typhi were present in all mononuclear cell platelet layer-positive cultures within 18 h of plating and were identified within an additional 10 min by a coagglutination technique. In contrast, identification of all positive cultures by conventional blood culture required 3 days. PMID- 2332480 TI - Interleukin-1 concentration in patients infected with human immunodeficiency virus. PMID- 2332481 TI - Relevant breakpoints for ticarcillin-clavulanic acid should be set primarily with data from ticarcillin-resistant strains. PMID- 2332482 TI - New expression of myelomonocytic antigens by microglia and perivascular cells following lethal motor neuron injury. AB - The results of the present study demonstrate that following lethal motor neuron injury microglia and perivascular cells, as well as brain macrophages derived from the latter two cell types, newly express antigens of the myelomonocytic lineage as recognized by the monoclonal antibodies ED1 and ED3. It is suggested that differences in the immunophenotype of resident brain macrophage precursor cells, i.e. microglia and perivascular cells, and macrophages occurring outside the central nervous system (CNS) may be explained by differences in local macrophage antigen expression rather than by a different embryological lineage. The new appearance of antigens common to peripheral macrophages on neural phagocytes in CNS lesions may therefore not necessarily imply that most or all of these cells are of recent blood origin. PMID- 2332483 TI - Zinc and thymic hormone-dependent immunity in normal ageing and in patients with senile dementia of the Alzheimer type. AB - Plasma zinc levels were measured in young controls, aged controls, patients with dementia of the Alzheimer type and patients with non-Alzheimer type dementia. Zinc levels decreased with age; however, no difference was found between patients with dementia and age-matched controls. Plasma levels of active or inactive thymulin, a nonapeptide produced and released by the thymus gland, were also determined in young controls, aged controls, patients with dementia of the Alzheimer type and patients with non-Alzheimer type dementia. Basal levels of active thymulin were decreased in aged controls and in patients with dementia. In vitro reactivation of thymulin after zinc addition to plasma samples was decreased in aged controls. A further impairment of thymulin reactivation was present in patients with dementia. A significant age-dependent decrease in lymphocyte proliferation after mitogen stimulation was found; however, no difference was present between aged controls and patients with dementia of the Alzheimer type. Interleukin-2-induced cell activation and its effect on mitogen induced proliferation were also measured; once again only an age-associated decrease was found. The endocrine function of the thymus of patients with dementia appears to be more compromised than that from aged controls. PMID- 2332484 TI - The effects of irradiation on major histocompatibility complex expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model. AB - The effects of irradiation on major histocompatibility complex (MHC) expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model were examined. Doses of irradiation administered were biologically equivalent to that used in the treatment of patients with malignant gliomas. No significant change in immune parameters was observed following irradiation in the normal rat brain. In the 9L gliosarcoma model irradiation did not suppress MHC expression or lymphocytic infiltration. These findings suggest that prior exposure to therapeutic irradiation need not adversely affect subsequent immunotherapies, and provide a foundation for future studies of immunomodulation in the irradiated brain. PMID- 2332485 TI - The IOM report, The Future of Public Health. PMID- 2332486 TI - "And the band played on". PMID- 2332487 TI - Air bags and auto safety. PMID- 2332488 TI - The incorporation of practice into graduate education for public health. AB - From their inception, the schools of public health placed a high priority on the education of practitioners. This article briefly explores the reasons for the growing perceptions that there is a gulf between education and practice, cites the practical barriers to reducing the gulf, and suggests methods that must be used by practitioners and educators to better integrate practice into graduate education for public health. PMID- 2332489 TI - The passage of Maryland's gun law: data and advocacy for injury prevention. AB - In 1988 the Maryland legislature passed an innovative law designed to limit the availability of certain types of handguns within the state. Pro-gun forces opposed the law and gathered the requisite number of petitioning signatures to refer the law to a public referendum on election day. The months preceding the referendum saw intense political campaigning over the gun law, with pro-gun forces spending $6.6 million, more money than had ever been spent in a Maryland political campaign. The handgun law was recognized to be a public health issue. This article reviews the activity involved in the passage of the law and the referendum, and discusses the role played by the Johns Hopkins injury prevention faculty in providing information to decision makers. PMID- 2332490 TI - Occupational health: a classic example of class conflict. AB - The history of class conflict in occupational health in the United States is illustrated by the current Pittston Company attack on coal miners' health benefits, the silicosis and asbestosis controversies, the corporate restrictions on state workers' compensation laws, and the unremitting management opposition to the federal Coal Mine Health and Safety Act of 1969 and the Occupational Health and Safety Act of 1970. A positive action program is presented as the basis for convening the long-overdue White House Conference on Occupational Health and Safety. Mining engineers are urged to support that action program to prevent unnecessary work-related death and disability. PMID- 2332491 TI - For profits: a look at the bottom line. AB - This paper examines the expansion of for-profit health care organizations, focusing on hospitals. It argues that much of the support of for-profits derives from American market ideology and the assumption that the search for profits leads to efficiency in production. In the health field, there is no evidence, however, that such gains in efficiency exist or that, if they do, they are shared with patients in the form of lower costs of care or with employees in the form of higher wages. The paper presents a number of reasons for concluding that for profits would not serve the needs of patients, care deliverers, local communities, or the health care system. Potential efficiency gains, even if realized, would be far outweighed by the damage that for-profits would cause. PMID- 2332492 TI - Ethical essentials of a national health program. PMID- 2332493 TI - The nursing shortage and provider attitudes: a political perspective. AB - The nursing shortage has been labeled a significant crisis in the health sector. This shortfall could severely threaten both the nursing profession and the entire American health care system. Numerous studies have focused on nurses' satisfaction with their work and the factors leading to positive and negative evaluations. A major deficiency of these endeavors, however, is that none have examined the attitudes of the nurses toward the shortage nor the activities which might be undertaken to rectify it. Moreover, political competence and the nurses' perceptions of the political arena have not been addressed and related to the shortage. The purpose of this paper is to help fill these gaps in the literature. PMID- 2332494 TI - Modifying clinical practice: two initiatives in the English National Health Service. AB - Two information systems in the English National Health Service (NHS) are described and discussed. The performance indicator scheme enables service inputs and activity to be readily compared between district health authorities (DHAs) or hospitals. Quality of care is not measured directly by performance indicators but in certain circumstances a limited assessment may be inferred from the health service input and activity data. Experiments in management budgeting and resource management are reported in which the NHS accounting system is being changed to one which is more patient-based and from which costs can be identified for clinically meaningful groups of patients. Variation in service activity, derived from the performance indicator system, has been used by the government with other evidence to make the case for NHS reform. Realistic implementation of the proposed NHS reforms will depend on the success of the budgeting experiments. PMID- 2332495 TI - Autonomic pathophysiology in heart failure patients. Sympathetic-cholinergic interrelations. AB - We conducted this study in an effort to characterize and understand vagal abnormalities in heart failure patients whose sympathetic activity is known. We measured sympathetic (peroneal nerve muscle sympathetic recordings and antecubital vein plasma norepinephrine levels) and vagal (R-R intervals and their standard deviations) activities in eight heart failure patients and eight age matched healthy volunteers, before and after parasympathomimetic and parasympatholytic intravenous doses of atropine sulfate. At rest, sympathetic and parasympathetic outflows were related reciprocally: heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows. Low dose atropine, which is known to increase the activity of central vagal-cardiac motoneurons, significantly increased R-R intervals in healthy subjects, but did not alter R-R intervals in heart failure patients. Thus, our data document reciprocal supranormal sympathetic and subnormal parasympathetic outflows in heart failure patients and suggest that these abnormalities result in part from abnormalities within the central nervous system. PMID- 2332496 TI - Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen. AB - Ro/SS-A antibodies are found in a number of human autoimmune disorders including Sjogren's syndrome and several systemic lupus erythematosus-related disorders. These heterogeneous autoantibodies are known to recognize several distinct cellular antigens. With synthetic oligonucleotides corresponding to amino acid sequence information we have isolated a full-length cDNA clone which encodes a human Ro ribonucleoprotein autoantigen. The 1,890-base pair clone contains an open reading frame that encodes a 417-amino acid, 48-kD polypeptide that migrates aberrantly at 60 kD by SDS-PAGE. Rabbit antibodies raised against this protein's recently described amino-terminal epitope react with a previously identified 52 kD human Ro protein and immunoprecipitate the human cytoplasmic RNAs. Ultraviolet light cross-linking studies suggest that this Ro protein binds each of the four major human cytoplasmic RNAs. The deduced amino acid sequence is 63% homologous to an Onchocerca volvulus antigen. Southern filter hybridization analysis indicates that this gene is not highly polymorphic and exists as a single copy in the human genome. Chromosomal localization studies place this gene on the short arm of chromosome 19 near the gene encoding the low density lipoprotein receptor. PMID- 2332497 TI - Amniotic fluid interleukin 6 in preterm labor. Association with infection. AB - To evaluate whether IL-6 participates in the host response to intrauterine infection, we studied IL-6 bioactivity and isoforms in amniotic fluid (AF). Two different assays for IL-6 were used: the hepatocyte stimulating factor assay (in Hep3B2 cells) and the SDS-PAGE/immunoblot assay. IL-6 determinations were performed in 205 AF samples. Samples were obtained from patients in the midtrimester of pregnancy (n = 25), at term with no labor (n = 31), at term in active labor (n = 40), and from patients in preterm labor (n = 109). Higher AF IL 6 levels were observed in women in preterm labor with intraamniotic infection than in women in preterm labor without intraamniotic infection (median = 375 ng/ml, range = 30-5000 ng/ml vs. median = 1.5 ng/ml, range = 0-500, respectively, P less than 0.0001). The 23-25- and 28-30-kD IL-6 species could be readily detected in SDS-PAGE immunoblots performed directly on 10-microliters aliquots of AF from patients with intraamniotic infection. Among women in preterm labor with culture-negative AF, those who failed to respond to subsequent tocolytic treatment had higher AF IL-6 concentrations than those who responded to therapy (median = 50 ng/ml vs. median = 1.2 ng/ml, respectively, P less than 0.05). Only low levels of IL-6 were detected in AF obtained from normal women in the midtrimester and third trimester of pregnancy. Decidual tissue explants obtained from the placentas of women undergoing elective cesarean section at term without labor (n = 11) produced IL-6 in response to bacterial endotoxin. In a pilot study, AF IL-6 was determined in 56 consecutive women admitted with preterm labor. All patients (n = 10) with elevated AF IL-6 (cutoff = 46 ng/ml) delivered a premature neonate. 4 of these 10 patients had positive AF cultures for microorganisms. These studies implicate IL-6 in the host response to intrauterine infection and suggest that evaluation of AF IL-6 levels may have diagnostic and prognostic value in the management of women in preterm labor. PMID- 2332498 TI - Effects of hypernatremia on organic brain osmoles. AB - We studied the effects of varying degrees and durations of hypernatremia on the brain concentrations of organic compounds believed to be important, so-called "idiogenic" osmoles in rats by means of conventional biochemical assays, nuclear magnetic resonance spectroscopy, and high-performance liquid chromatography. There were no changes in the concentrations of these osmoles (specifically myoinositol, sorbitol, betaine, glycerophosphorylcholine [GPC], phosphocreatine, glutamine, glutamate, and taurine) in rats with acute (2 h) hypernatremia (serum Na 194 +/- 5 meq/liter). With severe (serum Na 180 +/- 4 meq/liter) chronic (7 d) hypernatremia, the concentrations of each of these osmoles except sorbitol increased significantly: myoinositol (65%), betaine (54%), GPC (132%), phosphocreatine (73%), glutamine (143%), glutamate (84%), taurine (78%), and urea (191%). Together, these changes account for 35% of the change in total brain osmolality. With moderate (serum Na 159 +/- 3 meq/liter) hypernatremia, more modest but significant increases in the concentrations of each of these osmoles except betaine and sorbitol were noted. When rats with severe chronic hypernatremia were allowed to drink water freely, their serum sodium as well as the brain concentrations of all of these organic osmoles except myoinositol returned to normal within 2 d. It is concluded that: idiogenic osmoles play an important role in osmoregulation in the brain of rats subjected to hypernatremia; the development of these substances occur more slowly than changes in serum sodium; and the decrease in concentration of myoinositol occurs significantly more slowly than the decrease in serum sodium which occurs when animals are allowed free access to water. These observations may be relevant to the clinical management of patients with hypernatremia. PMID- 2332499 TI - Impairment of sympathetic activation during static exercise in patients with muscle phosphorylase deficiency (McArdle's disease). AB - Static exercise in normal humans causes reflex increases in muscle sympathetic nerve activity (MSNA) that are closely coupled to the contraction-induced decrease in muscle cell pH, an index of glycogen degradation and glycolytic flux. To determine if sympathetic activation is attenuated when muscle glycogenolysis is blocked due to myophosphorylase deficiency (McArdle's disease), an inborn enzymatic defect localized to skeletal muscle, we now have performed microelectrode recordings of MSNA in four patients with McArdle's disease during static handgrip contraction. A level of static handgrip that more than doubled MSNA in normal humans had no effect on MSNA and caused an attenuated rise in blood pressure in the patients with myophosphorylase deficiency. In contrast, two nonexercise sympathetic stimuli, Valsalva's maneuver and cold pressor stimulation, evoked comparably large increases in MSNA in patients and normals. The principal new conclusion is that defective glycogen degradation in human skeletal muscle is associated with a specific reflex impairment in sympathetic activation during static exercise. PMID- 2332500 TI - Abnormal regulation of renal vitamin D catabolism by dietary phosphate in murine X-linked hypophosphatemic rickets. AB - Hyp mice exhibit increased renal catabolism of vitamin D metabolites by the C-24 oxidation pathway (1988. J. Clin. Invest. 81:461-465). To examine the regulatory influence of dietary phosphate on the renal vitamin D catabolic pathway in Hyp mice, we measured C-24 oxidation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in renal mitochondria isolated from Hyp mice and normal littermates fed diets containing 0.03% (low-Pi), 1% (control-Pi), and 1.6% (high-Pi) phosphate. In normal mice the low-Pi diet led to a rise in serum 1,25(OH)2D (22.2 +/- 1.8 to 48.1 +/- 6.8 pg/ml, P less than 0.05) and no change in C-24 oxidation products (0.053 +/- 0.006 to 0.066 +/- 0.008 pmol/mg protein per min) when compared with the control diet. In Hyp mice the low-Pi diet elicited a fall in serum 1,25(OH)2D (21.9 +/- 1.2 to 8.0 +/- 0.2 pg/ml, P less than 0.05) and a dramatic increase in C-24 oxidation products (0.120 +/- 0.017 to 0.526 +/- 0.053 pmol/mg protein per min, P less than 0.05) when compared with the control diet. The high-Pi diet did not significantly alter serum levels of 1,25(OH)2D or C-24 oxidation products in normal mice. Hyp mice on the high-Pi diet experienced a rise in serum 1,25(OH)2D (21.9 +/- 1.2 to 40.4 +/- 7.3, P less than 0.05) and a fall in C-24 oxidation products (0.120 +/- 0.017 to 0.043 +/- 0.007 pmol/mg protein per min, P less than 0.05). The present results demonstrate that the defect in C-24 oxidation of 1,25(OH)2D3 in Hyp mice is exacerbated by phosphate depletion and corrected by phosphate supplementation. The data suggest that the disorder in vitamin D metabolism in the mutant strain is secondary to the perturbation in phosphate homeostasis. PMID- 2332501 TI - Mechanism of myocardial contractile depression by clinical concentrations of ethanol. A study in ferret papillary muscles. AB - Moderate alcohol intoxication in man, a ubiqitious social event, causes acute but reversible myocardial depression, the mechanism of which is unknown. We investigated whether this depression could be due to a direct effect of ethanol on the process of electromechanical coupling by simultaneously measuring the transmembrane action potential and contraction, or the cytosolic calcium transient (via aequorin photoluminescence) and contraction in isolated ferret right ventricular papillary muscle. Ethanol, in concentrations that are similar to plasma levels in man during intoxication (0.15 vol %), depressed the force of contraction approximately 10%. The step in the electromechanical process that was affected appeared to be the calcium-myofilament interaction, as there was no change in the transmembrane action potential or cytosolic calcium transient. This inhibition was quickly reversed by removal of the ethanol from the perfusate. On the other hand, higher concentrations of ethanol produced changes in contraction, the calcium transient, and the action potential, suggesting multiple levels of inhibition of electromechanical coupling. Increasing the perfusate calcium or use of the calcium channel agonist, BAY-K 8644, increased cytosolic calcium to near maximum but had little effect on contractility, confirming that the relationship between calcium and the myofilaments had been altered. These data suggest that the acute depression in ventricular function seen with alcohol consumption may be due to a direct effect on electromechanical coupling through inhibition of the calcium myofilament interaction. PMID- 2332502 TI - CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity. AB - CAP37, an antimicrobial protein of human neutrophil granules, is a specific chemoattractant for monocytes. Purified to homogeneity by sequential chromatography over carboxymethyl Sephadex, G-75 Sephadex, and hydrophobic interaction HPLC, demonstratively endotoxin-free CAP37 was maximally chemotactic over a range of 1.3 X 10(-9)-10(-8) M. Thus it was active in the same molar concentrations as formyl-methionyl-leucyl-phenylalanine. CAP37 lacked chemotactic activity for neutrophils and lymphocytes. In checkerboard assays CAP37 had some chemokinetic activity as well. It was also chemotactic for rabbit mononuclear cells. Higher concentrations (2.7 X 10(-8) M) were required for activity with rabbit cells than with human. Sequence analysis of the first 42 NH2-terminal amino acid residues of CAP37 showed strong homologies with known serine proteases that mediate various functions in inflammation. However, a critical substitution of a serine for a histidine at position 41 suggested that CAP37 lacked serine protease action. This impression was supported by the failure of CAP37 to bind tritiated diisopropyl fluorophosphate. 89% of total CAP37 was released extracellularly from human neutrophils while they phagocytized Staphylococcus aureus. We propose that CAP37 released from neutrophils during phagocytosis and degranulation may mediate recruitment of monocytes in the second wave of inflammation. PMID- 2332503 TI - Immunogenic DNA-related factors. Nucleosomes spontaneously released from normal murine lymphoid cells stimulate proliferation and immunoglobulin synthesis of normal mouse lymphocytes. AB - The cell-free supernatants of normal spleen and thymus lymphocytes in short-term culture release low molecular weight (LMW) DNA protein molecules that have an immunoproliferative effect (polyclonal B cell activation) in vitro. We have determined that the protein-LMW DNA complexes responsible for these effects are nucleosomal constituents of chromatin, since the mitogenically active fractions of these cell-free supernatants contain the constituents of core histones (H3, H2A, H2B, H4) together with LMW DNA (140-180 bp), and since the immunoproliferative effects of these cell-free supernatants could be mimicked by various other nucleoprotein preparations (including calf thymus and chicken erythrocyte nucleosomes). The spontaneous cellular release of cleaved chromatin constituents in vitro can be attributed to a form of programmed cell death termed apoptosis, since the cultured spleen cells exhibited (a) morphologic evidence consistent with this process by electron microscopy, and (b) evidence of intracellular cleavage of chromatin which, like apoptosis, could be blocked with ZnSO4. This resulted in inhibition of the extracellular release of nucleosomal constituents as well as the immunoproliferative effects of the cell-free supernatants. The immunoproliferative effect of nucleosomes released from cells during apoptosis could be responsible for previously observed spontaneous in vitro anti-DNA and anti-histone antibody responses of murine spleen cells, and in vivo in normal lymphoid tissues, resulting in renewed cellular proliferation after cell death. In pathological states, this could result in abnormal polyclonal B cell proliferation and autoantibody formation. PMID- 2332504 TI - A single nucleotide substitution introduces a premature termination codon into the androgen receptor gene of a patient with receptor-negative androgen resistance. AB - Mutations of the androgen receptor that impair the action of 5 alpha dihydrotestosterone and testosterone result in abnormal male sexual development. The definition of the organization of the androgen receptor gene has permitted us to examine its structure in nine patients with androgen resistance that exhibit absent 5 alpha-dihydrotestosterone binding in cultured fibroblasts (receptor negative androgen resistance). Using labeled probes specific for each individual coding exon, we find no gross rearrangements, insertions, or deletions of the androgen receptor gene in these patients. To analyze the genetic defect in these receptor-negative patients, we used the polymerase chain reaction to amplify each individual exon of the androgen receptor gene in nine affected patients. In all patients, the size of each amplified exon segment was identical to that in normal individuals. The nucleotide sequence of the entire coding region of the androgen receptor was determined in one of these patients. A single nucleotide substitution was identified that results in a premature termination codon in exon 6 at amino acid 794. S1 nuclease protection assays demonstrated that normal levels of androgen receptor mRNA are present in skin fibroblasts of this patient. Transfection of a mutated androgen receptor cDNA containing a termination codon at position 794 into eukaryotic cells resulted in formation of a normal amount of receptor protein, as indicated by immunoblotting, but the expressed protein does not bind 5 alpha-dihydrotestosterone. These findings suggest that the presence of a premature termination codon at amino acid 794 of the androgen receptor is the cause of androgen resistance in this patient. PMID- 2332505 TI - X-linked severe combined immunodeficiency. Diagnosis in males with sporadic severe combined immunodeficiency and clarification of clinical findings. AB - Over 80% of infants with severe combined immunodeficiency (SCID) of unknown genetic etiology are males, yet less than a third of these affected males have a family history of X-linked disease. To help identify new mutations of the X linked SCID gene and to provide genetic counseling, X chromosome inactivation patterns in T cells from 16 women who had sons with sporadic SCID were examined. Between 9 and 35 human/hamster hybrids that selectively retained the active human X chromosome were produced from the T cells of each woman and analyzed with an X linked restriction fragment length polymorphism for which the woman in question was heterozygous. Exclusive use of a single X as the active X was seen in the T cell hybrids from 7 of the 16 women, identifying these women as carriers of X linked SCID. Studies on additional family members confirmed the mutant nature of the inactive X and revealed the source of the new mutation in three families. To determine whether there were any laboratory characteristics that might differentiate the boys whose mothers were identified as carriers of X-linked SCID from those whose mothers were not, the clinical records of both groups were compared to each other and to a group of 14 boys with a family history of X linked SCID. The most consistent finding in the 21 patients with X-linked SCID was an elevated proportion of B cells. These data demonstrate the high incidence of spontaneous mutation for the X-linked SCID gene and help clarify the characteristic presenting features of this disorder. PMID- 2332506 TI - Chromogranin A in children with neuroblastoma. Serum concentration parallels disease stage and predicts survival. AB - Chromogranin A is an acidic protein costored and coreleased with catecholamines from storage vesicles. Its serum concentration is elevated in patients with peptide-producing endocrine neoplasia. We measured serum chromogranin A at the time of diagnosis in 34 children with all stages of neuroblastoma. With a sensitivity of 91% and specificity of 100%, serum chromogranin A emerged as a useful diagnostic tool for neuroblastoma, comparable to or better than other measurements such as neuron-specific enolase, ferritin, or dopamine-beta hydroxylase. Mean serum chromogranin A correlated with disease stage (r = 0.76, P less than 0.01). The relationship of prognosis (progression-free survival) to baseline serum chromogranin A, age, and disease stage was determined in 34 patients at risk for relapse, with a median followup period of 18 mo (range, 1-48 mo). The survival rate for patients with lower serum chromogranin A levels (less than 190 ng/ml at the time of diagnosis) was 69%, whereas it was 30% for those with higher chromogranin A levels (P less than 0.05). Furthermore, when subjects were additionally stratified by either age or stage, chromogranin A was an effective prognostic tool in patients who either were older than 1 yr (P less than 0.005) or had more advanced disease (stage III or IV; P less than 0.05). We conclude that serum chromogranin A in neuroblastoma is (a) a valuable (sensitive and specific) diagnostic tool, (b) a correlate of tumor burden, and (c) a useful predictor of survival. PMID- 2332507 TI - Effects of interleukin-3 on hematopoietic recovery after 5-fluorouracil or cyclophosphamide treatment of cynomolgus primates. AB - Interleukin-3 (IL-3) is a hematopoietic growth factor that supports the growth of early hematopoietic progenitors in vitro. In vivo administration of recombinant human interleukin-3 (rhIL-3) to normal primates results in a modest and delayed leukocytosis secondary to increases in neutrophils, basophils, and eosinophils. We postulated that the effects of rhIL-3 might be more pronounced in hematologically stressed primates, and therefore administered rhIL-3 to primates after intensive myelosuppressive therapy. Primates received either cyclophosphamide (CPM) at 60 mg/kg or 5-fluorouracil (5-FU) at 75 mg/kg i.v. on two consecutive days. Subsequently, rhIL-3 was administered intravenously or subcutaneously at 20 micrograms/kg per d for 14 d. Compared to controls, all rhIL 3 treated primates experienced higher absolute neutrophil count (ANC) nadirs and dramatic decreases in the period of severe neutropenia (ANC less than 500) after myelosuppressive therapy. RhIL-3 administration resulted in a significant basophilia and eosinophilia, which resolved after discontinuation of the drug. RhIL-3 did not enhance erythroid recovery. Platelet recovery was earlier in rhIL 3-treated animals. However, variations in the platelet recovery observed in control animals, precluded accurate estimation of this effect or its significance. Our results indicate that the administration of rhIL-3 following intensive myelosuppressive therapy dramatically enhances myeloid recovery and ablates the predicted period of prolonged severe neutropenia. PMID- 2332508 TI - Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium. AB - Experiments were performed in human working myocardium to investigate the relationship of intracellular calcium handling and availability to alterations in the strength of contraction produced by changes in stimulation rate and pattern. Both control and myopathic muscles exhibited potentiation of peak isometric force during the postextrasystolic contraction which was associated with an increase in the peak intracellular calcium transient. Frequency-related force potentiation was attenuated in myopathic muscles compared to controls. This occurred despite an increase in resting intracellular calcium and in the peak amplitude of the calcium transient as detected with aequorin. Therefore, abnormalities in contractile function of myopathic muscles during frequency-related force potentiation are not due to decreased availability of intracellular calcium, but more likely reflect differences in myofibrillar calcium responsiveness. Sarcolemmal calcium influx may also contribute to frequency-related changes in contractile force in myopathic muscles as suggested by a decrease in action potential duration with increasing stimulation frequency which is associated with fluctuations in peak calcium transient amplitude. PMID- 2332509 TI - Interaction between Borrelia burgdorferi and endothelium in vitro. AB - During the pathogenesis of Lyme disease, Borrelia burgdorferi spreads hematogenously from the site of a tick bite to several tissues throughout the body. The specific mechanism of spirochete emigration is presently unknown. Using cultured human umbilical vein endothelial cells, we found that Borrelia burgdorferi bound to the endothelial cells and to the subendothelial matrix. Low passage isolates adhered 22-30-fold greater than a strain maintained in culture continuously. Spirochete binding to subendothelial matrix was inhibited 48-63% by pretreatment of the matrix with anti-fibronectin antiserum. Spirochete migration across endothelial monolayers cultured on amniotic membrane was increased when the monolayers were damaged by chemical or physical means. Electron microscopic examination of spirochete-endothelial interactions demonstrated the presence of spirochetes in the intercellular junctions between endothelial cells as well as beneath the monolayers. Scanning electron microscopy identified a mechanism of transendothelial migration whereby spirochetes pass between cells into the amniotic membrane at areas where subendothelium is exposed. PMID- 2332511 TI - Radioimmunoassay of aescine, a mixture of triterpene glycosides. AB - A radioimmunoassay (RIA) has been developed for the determination of picogram amounts of aescine, an anti-inflammatory and anti-oedematous glycoside mixture from unpurified extracts of Aesculus hippocastanum. Practically no interference is observed for various potentially crossreacting compounds. This RIA covers the range 100 pg-50 ng, within which acceptable accuracy and precision are obtained. PMID- 2332510 TI - 2,4-Dienoyl-coenzyme A reductase deficiency: a possible new disorder of fatty acid oxidation. AB - Several inherited disorders of fatty acid beta-oxidation have been described that relate mainly to saturated precursors. This study is the first report of an enzyme defect related only to unsaturated fatty acid oxidation and provides the first in vivo evidence that fat oxidation in humans proceeds by the reductase dependent pathway. The patient was a black female, presenting in the neonatal period with persistent hypotonia. Biochemical studies revealed hyperlysinemia, hypocarnitinemia, normal organic acid profile, and an unusual acylcarnitine species in both urine and blood. The new metabolite was positively identified by mass spectrometry as 2-trans,4-cis-decadienoylcarnitine, derived from incomplete oxidation of linoleic acid. In spite of dietary therapy, the patient died of respiratory acidosis at four months of age. Samples of liver and muscle from the autopsy were assayed for 2,4-dienoyl-coenzyme A reductase activity. Using the substrate 2-trans,4-cis-decadienoylcoenzyme A, the reductase activity was 40% of the control value in liver and only 17% of that found in normal muscle. It is suggested that unsaturated substrates should be used for in vitro testing to cover the full range of potential beta-oxidation defects and that acylcarnitine species identification be used for in vivo detection of this disorder. PMID- 2332512 TI - Two ELISA methods for the measurement of airborne swine epithelial antigens. AB - A new double antibody sandwich ELISA for measuring swine epithelial antigens in swineries was compared to an adaption of our previously developed ELISA inhibition method. The sandwich ELISA is more sensitive than the inhibition ELISA, and its reproducibility is better. The quantitative results from swinery samples of the sandwich ELISA are about ten times higher, but correlate well (rs 0.88, p = 0.004) with the results of ELISA inhibition. The progression in magnitude of the results in relation to the sample dilution was examined. PMID- 2332513 TI - Immunoassay of theophylline by latex particle counting. AB - We set up an immunoassay by particle counting for theophylline. Theophylline concentration is assayed by its capacity to inhibit the agglutination of theophylline coated latex particles by a specific monoclonal antibody, the agglutination being enhanced by a rabbit anti-mouse IgG antiserum. The dose range is 2-64 mg/L. The cross-reactions observed with caffeine (0.3%), theobromine (0.2%), 3-methylxanthine (0.7%) and 8-chlorotheophylline (2%) are very good when compared with other published methods. Within and between-run precisions measured at low, medium and high level of the calibration curve show coefficients of variation ranging from 3.9% to 9.5%. Our assay was correlated with the Fluorescence Polarization Immunoassay (FPIA) and a correlation coefficient of 0.96 was determined for 89 samples. PMID- 2332514 TI - Value of the necropsy in perioperative deaths. AB - A series of 213 perioperative deaths was studied out of a total of 1451 consecutive necropsies carried out over three years. Discrepancies between the clinical and the necropsy diagnosis were assessed under four classes of discrepant diagnosis: class I, patient survival affected, treatable; class II, patient survival affected but not treatable; class III, correlated to cause of death but treatable; and class IV, incidental diagnosis which could not have been made before death. Major discrepancies of classes I and II were found in 44 (21%) and 62 (29%) cases, respectively. Minor discrepancies of classes III and IV were found in 63 (30%) and 101 (47%) cases, respectively. No discrepancies were found in 50 (23.5%) cases. These results confirm the continuing value of the necropsy in the assessment of perioperative deaths. PMID- 2332515 TI - Mast cells in leprosy skin lesions. AB - The variability of mast cell density within and between leprosy skin lesions was examined as a basis for future studies, and whether the number of mast cells in the lesion was determined by local or systemic factors was evaluated. The mast cell density in the granuloma, skin appendages, and intervening dermis was assessed by counting mast cells in glycol methacylate sections stained with Giemsa stain and relating these counts to area measurements obtained by planimetry. In biopsy specimens taken from the edge of established lesions the density of mast cells within the granulomata was considerably higher than that in the intervening dermis and was comparable with that found in the appendages. No major differences in mast cell density were found between unaffected skin and the centre or edge of individual lesions. Mast cell densities in biopsy specimens from the edge of different lesions on the same patient were also similar, suggesting that the mast cell density within the granulomata is independent of the site of the lesion and is determined systemically. PMID- 2332516 TI - Histopathology of acute human immunodeficiency virus exanthema. AB - Acute exanthema occurs in patients who are human immunodeficiency virus (HIV) positive before they become seropositive. The patients have influenza like symptoms and a macular skin rash on the upper trunk. Histopathological investigation of skin punch biopsy specimens from four patients with acute HIV exanthema showed a normal epidermis and a sparse dermal, mainly perivascular, lymphocytic/histiocytic infiltrate around vessels of the superficial plexus. Histopathological changes of the exanthema of acute HIV infection are non specific and resemble those of other acute viral exanthema, but when both the histopathological features and the clinical picture are suggestive, the clinician should take into consideration the possibility of HIV infection. PMID- 2332517 TI - Histological and immunohistochemical study of hepatitis B virus in human immunodeficiency virus infection. AB - Because the risk factors for human immunodeficiency virus (HIV) infection and hepatitis B (HBV) are similar and therefore coinfection is not uncommon, a detailed histological and immunohistochemical study of chronic hepatitis B infection in a group of 20 HIV positive Caucasian males (who did not have AIDS) and 30 HIV negative controls were undertaken. Using both the conventional histological classification and the Knodell histological activity index it was shown that HIV negative patients were more likely to have active disease and also more scarring than HIV positive patients. Hepatitis B surface antigen (HBsAg) expression was not significantly different between the two groups but expression of hepatitis Be antigen (HBeAg) and HBV-DNA polymerase was greater in those who were HIV positive. HIV positive patients are therefore more likely to have immunohistochemical markers of active viral replication, although histologically, liver disease is less severe. These findings have important implications for assessing the biopsy specimens in this group of patients and for treatment strategies aimed at improving their immune function. PMID- 2332519 TI - Role of nucleolar organiser regions in differentiating malignant from benign tumours of the colon. AB - An argyrophilic technique (AgNOR) was applied to paraffin wax sections of 12 tubular adenomas, 17 villous adenomas with moderate and severe atypia, and 21 colonic adenocarcinomas. The range of the mean number of nucleolar organiser regions (NORS) per nucleus was 1.54-3.28 (99% CI 2.29-3.04) for tubular adenomas 3.07-4.36 (2.98-4.43), and 3.60-5.02 (3.74-4.69) for villous adenomas with moderate and severe atypia, respectively, and 5.53-9.33 (6.15-8.54) for highly differentiated adenocarcinomas. The number of AgNORs permitted differentiation among the three groups. The differences observed were significant. Malignant tumour cells were characterised by a large number of AgNORs which were small in size and showed a scattered distribution. Nuclei of tubular adenoma and villous adenoma with moderate atypia had only a small number of large sized AgNORs in a clustered distribution. It is suggested that this method distinguishes malignant epithelial cells from benign cells of colon, even those with severe atypia, and that it is a useful adjunct to diagnostic histopathology. PMID- 2332518 TI - Idiopathic portal hypertension associated with cytotoxic drugs. AB - Four patients developed clinically important portal hypertension with histological features of idiopathic portal hypertension while they were receiving cytotoxic drugs for chronic myeloid leukaemia and Hodgkin's disease. Mild sclerosis of some small portal triads was the only abnormality seen at light microscopical examination in three of the four cases. In the remaining case light microscopical findings seemed to be normal. Two cases examined by electron microscopy showed perisinusoidal fibrosis; in one case this was the only abnormality detected. There is an association between idiopathic portal hypertension and the use of chemotherapeutic agents, particularly thioguanine. Adequate histological examination of liver tissue, including electron microscopic studies, is recommended for patients who develop hepatic problems while receiving cytotoxic treatment to elucidate this problem. PMID- 2332520 TI - Rate nephelometric determination of rheumatoid factor: comparison between Kallestad QM-300 and Beckman ICS-II (RF) methods. AB - The Kallestad Corporation recently suggested that their new buffer system for the nephelometric detection of rheumatoid factor conferred advantages over existing systems. Two rate nephelometric procedures, the Kallestad QM-300 and the Beckman ICS-II (RF), were therefore compared. Sera (n = 157) were selected on the basis of a previous ICS-II value. The results on the QM-300 of sera with an initial rheumatoid factor value of less than 400 IU identified two groups. Group 1 (n = 109) showed a good correlation with the ICS-II method while group 2 (n = 13) was highly discordant with the QM-300, producing significantly higher values. The values of 35 sera with an initial rheumatoid factor of greater than 400 IU were likewise highly discordant, with the QM-300 producing significantly lower values. Dilution recovery experiments implied that the Beckman buffer was likely to be contributory. As the formulae of the buffers remain proprietary, the reasons for the differences are speculative. The findings could be taken to indicate that the Kallestad value is a more accurate indicator of the quantity of rheumatoid factor than the Beckman value. PMID- 2332521 TI - Comparison of solid media for cultivation of anaerobes. AB - Two commercial agar media for the cultivation of anaerobes were compared with four other media for their ability to support the growth of a wide range of anaerobes from clinical specimens of subgingival plaque. Fastidious anaerobe agar (FAA, Lab M) and anaerobe agar (GAA, Gibco) allowed better growth of the pure cultures than the other media. FAA recovered the highest numbers of bacteria from subgingival plaque specimens which were composed predominantly of anaerobes. GAA performed poorly with these samples. It is concluded that FAA seemed to be superior to the other media tested for the cultivation and recovery of anaerobes. PMID- 2332522 TI - Rapid identification of Chlamydia psittaci and TWAR (C pneumoniae) in sputum samples using an amplified enzyme immunoassay. PMID- 2332523 TI - Evaluation of 3-fucosyl N-acetyllactosamine antibody staining in histological assessment of CIN. PMID- 2332524 TI - Serum IgE concentrations in complete Behcet's disease. PMID- 2332525 TI - New spiral bacterium in the gastric mucosa: Gastrospirillum hominis. PMID- 2332526 TI - Lack of significant effect of therapeutic propranolol on measurable platelet function in healthy subjects. PMID- 2332527 TI - Coexistence of corticotropin-releasing factor and enkephalin in the paraventricular nucleus of the rat. AB - Corticotropin-releasing factor and enkephalin-containing neurons are found in the paraventricular nucleus of the rat hypothalamus. Their immunocytochemical distribution suggests that a subpopulation of neurons of the paraventricular nucleus might contain both peptides. The present study describes the coexistence of corticotropin-releasing factor and enkephalin in parvicellular neurons of the paraventricular nucleus. Immunocytochemical labeling of peptides was combined with in situ hybridization of mRNA to visualize peptide and mRNA labeling in the same tissue section. This resulted in several observations: (1) neurons labeling for the peptide corticotropin-releasing factor also contain the mRNA to synthesize corticotropin-releasing factor, (2) neurons labeling for the peptide enkephalin also contain the mRNA to synthesize the peptide enkephalin, (3) a subpopulation of corticotropin-releasing factor neurons contains the mRNA to synthesize enkephalin, and (4) a subpopulation of enkephalin neurons contains the mRNA to synthesize corticotropin-releasing factor. A large percentage of enkephalin immunoreactive neurons contains corticotropin-releasing factor mRNA, whereas a smaller percentage of corticotropin-releasing factor immunoreactive neurons contains enkephalin mRNA. These double-labeled neurons are present throughout the rostral-caudal extent of the paraventricular nucleus; the majority of these neurons is present in the medial parvicellular paraventricular nucleus. PMID- 2332528 TI - Subnuclear organization of the lateral tegmental field of the rat. I: Nucleus ambiguus and ventral respiratory group. AB - Three classes of neurons within the lateral tegmental field of the rat medulla having different target projections were identified by retrograde labelling with three different fluorescent tracers. Labelled bulbospinal premotor and propriobulbar interneurons of the ventral respiratory group and vagal motoneurons of nucleus ambiguus formed partially intermingled longitudinal columns encompassed within a common region of the lateral tegmental field. Labelled neurons of each class were organized in a nonuniform distribution within these columns forming subdivisions distinguished by neuron morphology, orientation, and target projection. The three major rostrocaudal divisions of the ventral respiratory group (VRG) previously identified in the cat and rabbit were identified here in the rat, suggesting a common pattern of VRG organization among these species. PMID- 2332529 TI - Subnuclear organization of the lateral tegmental field of the rat. II: Catecholamine neurons and ventral respiratory group. AB - Bulbospinal and propriobulbar respiratory neurons of the ventral respiratory group and catecholamine neurons of the A1 and C1 cell groups were simultaneously labelled in the rat medulla by a combination of retrograde tracing and immunohistochemical identification. The ventral respiratory group and catecholamine cell groups form adjacent, parallel cell columns in the lateral tegmental field of the ventrolateral medulla. The ventral respiratory group is located immediately dorsal to the A1 and C1 groups, although some A1 neurons are intermingled with neurons of the rostral ventral respiratory group, and some C1 neurons are intermingled with those of the Botzinger complex. The proximate populations of respiratory, catecholamine, and (presumptive) cardiovascular neurons identified in this study provide further support to the hypothesis that this region of the lateral tegmental field of the ventrolateral medulla is a site of cardiorespiratory coordination. PMID- 2332530 TI - Expression of compartmentation antigen zebrin I in cerebellar transplants. AB - The mammalian cerebellum is divided into multiple parasagittal compartments as defined by the organization of afferent and efferent projections and by the pattern of expression of several biochemical markers. One such marker is the antigen zebrin I, a 120 kD polypeptide of unknown function that is expressed differentially by a subset of Purkinje cells. Zebrin I+ Purkinje cells are grouped into an array of 14 parasagittal bands interposed by zebrin I- compartments. This Purkinje cell compartmentation corresponds to compartments in the olivocerebellar projection. The afferent axon compartments are present prior to the expression of the mature zebrin I phenotype, thus raising the possibility that differential afferent input regulates the zebrin I phenotype of the target of that input. Lesion studies in the neonate preclude a role for afferent inputs in the regulation of zebrin I expression postnatally, but a prenatal role in commitment still remains open. To explore this possibility, cerebellar anlagen were dissected from embryos at embryonic days 12-15, that is, prior to any contact with afferents, and transplanted ectopically into adult hosts. In the first series of experiments, the grafts were placed into the anterior chamber of the eye, and in the second series, into cavities prepared in the neocortex. Grafts were allowed to mature and then were immunoperoxidase or immunofluorescence stained for zebrin I immunoreactivity. Zebrin I was expressed by grafted Purkinje cells in cortico and in oculo. Double-labelling experiments confirmed that both the zebrin I+ and the zebrin I- phenotypes were present. The zebrin I immunoreactivity revealed that the zebrin I+ Purkinje cells resemble those in situ with an extensive dendritic arborization that extends through the molecular layer perpendicular to the long axes of the folia. In conclusion, the present data suggest that afferent input does not play a role in the determination of the zebrin I phenotype of Purkinje cells. PMID- 2332531 TI - Synaptic organization of neurotensin immunoreactive amacrine cells in the chicken retina. AB - Immunohistochemistry was utilized to investigate the light and electron microscopic localization of neurotensinlike immunoreactive (NT) amacrine cells in the chicken retina. The NT cells possess oval cell bodies (7 microns in diameter) that are located in either the second or third tier of cells from the border of the inner nuclear and inner plexiform layers. The processes of such cells extend into the inner plexiform layer where they ramify as a narrow plexus in sublamina 1 and as a broad plexus in sublaminas 3 and 4. Additionally, stained processes are observed occasionally within sublamina 5. At the ultrastructural level, NT positive somas exhibit a rather dense and evenly distributed peroxidase reaction product throughout their cytoplasm. The nucleus of NT amacrine cells possess a round, unindented nuclear membrane. NT-immunoreactive processes in the inner plexiform layer interact synaptically only with non-NT cells. NT processes receive synaptic input mainly from the processes of amacrine cells and to a lesser degree from bipolar cells. The large majority of NT-stained varicosities form presynaptic contacts onto the processes of amacrine cells, but are also presynaptic to bipolar cell axon terminals. Moreover, each of the above synaptic relationships can be identified in each of sublaminas 1 and 3 to 4 of the inner plexiform layer. In addition, NT processes are presynaptic to processes devoid of synaptic vesicles that may originate from ganglion cells. Finally, NT processes occasionally form synaptic contacts onto somas situated in the most proximal row of the inner nuclear layer. PMID- 2332532 TI - Topographic organization in the corticocortical connections of medial agranular cortex in rats. AB - Medial agranular cortex (AGm) is a narrow, longitudinally oriented region known to have extensive corticortical connections. The rostral and caudal portions of AGm exhibit functional differences that may involve these connections. Therefore we have examined the rostrocaudal organization of the afferent cortical connections of AGm by using fluorescent tracers, to determine whether there are significant differences between rostral and caudal AGm. Mediolateral patterns have also been examined in order to compare the pattern of corticocortical connections of AGm to those of the laterally adjacent lateral agranular cortex (AGl) and medially adjacent anterior cingulate area (AC). In the rostrocaudal domain, there are notable patterns in the connections of AGm with somatic sensorimotor, visual, and retrosplenial cortex. Rostral AGm receives extensive afferents from the caudal part of somatic sensorimotor area Par I, whereas caudal AGm receives input largely from the hindlimb cortex (area HL). Middle portions of AGm show an intermediate condition, indicating a continuously changing pattern rather than the presence of sharp border zones. The whole of the second somatic sensorimotor area Par II projects to rostral AGm, whereas caudal AGm receives input only from the caudal portion of Par II. Visual cortex projections to AGm originate in areas Oc1, Oc2L and Oc2M. Connections of rostral AGm with visual cortex are noticeably less dense than those of mid and caudal AGm, and are focused in area Oc2L. The granular visual area Oc1 projects almost exclusively to mid and caudal AGm. Retrosplenial cortex has more extensive connections with caudal AGm than with rostral AGm, and the agranular and granular retrosplenial subregions are both involved. Other cortical connections of AGm show little or no apparent rostrocaudal topography. These include afferents from orbital, perirhinal, and entorhinal cortex, all of which are bilateral in origin. In the mediolateral dimension, AGm has more extensive corticocortical connections than either AGl or AC. Of these three neighboring areas, only AGm has connections with the somatic sensorimotor, visual, retrosplenial and orbital cortices. In keeping with its role as primary motor cortex, AGl is predominantly connected with area Par I of somatic sensorimotor cortex, specifically rostral Par I. AGl receives no input from visual or retrosplenial cortex. Anterior cingulate cortex has connections with visual area Oc2 and with retrosplenial cortex, but none with somatic sensorimotor cortex. Orbital cortex projections are sparse to AGl and do not appear to involve AC.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2332533 TI - Efferent projections of the subthalamic nucleus in the squirrel monkey as studied by the PHA-L anterograde tracing method. AB - The organization of the efferent connections of the subthalamic nucleus was studied in the squirrel monkey (Saimiri sciureus) by using the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) as an anterograde tracer. At the level of the basal forebrain, anterogradely labeled fibers and axon terminals were mostly found in the striatopallidal complex and the substantia innominata. In cases in which the PHA-L injection sites were placed in the central or the lateral third of the subthalamic nucleus, numerous anterogradely labeled fibers were seen to arise from the injection loci and innervate massively the globus pallidus. At pallidal levels the fibers formed bands lying parallel and adjacent to the medullary laminae. The number and the complexity of the topographical organization of these bands varied with the size and the location of the PHA-L injection site. When examined at a higher magnification, the bands of subthalamopallidal fibers appeared as rich plexuses of short axon collaterals with small bulbous enlargements that closely surrounded the cell bodies and primary dendrites of pallidal cells. In contrast, PHA-L injection involving the medial tip of the subthalamic nucleus did not produce bandlike fiber patterns in the globus pallidus. Instead, the labeled fibers formed a diffuse plexus occupying the ventral part of the rostral pole of the globus pallidus as well as the subcommissural pallidal region. The substantia innominata contained a moderate number of labeled fibers and axon terminals following injection of PHA-L in the medial tip of the subthalamic nucleus. A small to moderate number of anterogradely labeled fibers were seen in the putamen after all PHA-L injections. These subthalamostriatal fibers were long, linear, and branched infrequently. At midbrain level the substantia nigra contained a significant number of anterogradely labeled fibers and axon terminals following PHA-L injection in the subthalamic nucleus. The subthalamonigral fibers descended along the ventromedial part of the cerebral peduncle and swept laterally to reach their target. Most of these fibers formed small plexuses along the base of the pars reticulata, whereas a few others ascended along the cell columns of the pars compacta that impinged deeply within the pars reticulata. More caudally in the brainstem, a small number of fibers occurred in the area of the pedunculopontine nucleus and in the periaqueductal gray. These findings indicate that besides its well-known connection with the pallidum, the subthalamic nucleus gives rise to widespread projections to other components of the basal ganglia in primates. PMID- 2332534 TI - Abstracts of the British Intensive Care Society, autumn meeting. London, October 21, 1989. PMID- 2332535 TI - Multiple organ failure--a role for plasma exchange? AB - Two patients with multiple organ failure, septicaemia and a deteriorating clinical course were treated by plasma exchange in addition to standard supportive measures. Dramatic improvements were seen in cardio-respiratory (patient 1), neurological and renal parameters (patient 2) which were attributable to the exchanges. Plasma exchange might be of value as adjunctive therapy where overwhelming septicaemia occurs with multiple organ failure. PMID- 2332536 TI - Respiratory and hemodynamic effects of halothane in status asthmaticus. AB - The respiratory and hemodynamic effects of halothane in patients with status asthmaticus who required mechanical ventilation was evaluated. Halothane was administered in 12 patients in a concentration of 1% for thirty minutes. Standard drug treatments and ventilator settings were not modified during halothane administration. The following data were collected before and after halothane administration: arterial blood gases, peak inspiratory pressure, VD/VT, pulmonary arterial pressure, right heart pressures and cardiac index (by means of the thermodilution method). After halothane treatment PaCO2 significantly decreased, arterial pH increased, peak inspiratory pressure decreased and VD/VT decreased significantly. Mean pulmonary arterial pressure and right heart pressures decreased and the cardiac index was unchanged. The heart rate significantly decreased and arrhythmias did not occur during halothane administration. The administration of halothane in patients with status asthmaticus requiring mechanical ventilation produces a rapid reduction in bronchospasm and barotraumatic injury and a rapid improvement in arterial blood gases, without any adverse hemodynamic effects. PMID- 2332537 TI - Dose-response effects and time course of effects of inhaled fenoterol on respiratory mechanics and arterial oxygen tension in mechanically ventilated patients with chronic airflow obstruction. AB - To investigate the dose-response relationship and the time course of the effects of fenoterol (a selective beta 2-adrenergic agonist) on respiratory function in mechanically ventilated patients with acute respiratory failure due to exacerbation of chronic airflow obstruction (CAO), seven consecutive acutely ill patients were studied within 3 days of the onset of mechanical ventilation. Airflow, airway pressure, and changes in lung volume were measured with the transducers of the 900 C Servo Ventilator, the last by electronic integration. The end-expiratory lung volume (EELV), the intrinsic positive end-expiratory pressure (PEEPi), the static respiratory compliance (Cstrs), maximum and minimum respiratory resistance (Rrsmax and Rrsmin), and arterial oxygen tension (PaO2), were measured under control conditions (all patients were receiving aminophylline infused at a constant rate) 5, 15, and 30 min after administration of 4 ml aerosolized saline solution and 5, 15, and 30 min after inhalation of 0.4, 0.8, and 1.2 mg fenoterol. After the last dose, measurements were repeated at 60, 120, and 180 min. We found that, on average, while saline did not cause any significant change in respiratory mechanics, a low dose (0.4 mg) of inhaled fenoterol was followed by a rapid (5 min) and significant decrease in Rrsmax ( 33%), Rrsmin (-28%), EELV (-34%), and PEEPi (-44%), with a slight but not significant further fall with higher doses. However, changes were short-lasting, and by 2 h after the end of administration were no longer significant. PaO2 dropped significantly on average, with a maximum mean fall of 15 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332538 TI - Measurement of extravascular lung water by thermal-dye dilution technique: mechanisms of cardiac output dependence. AB - The extent to which extravascular lung water (EVLW) is dependent on cardiac output was analysed in anaesthetized and mechanically ventilated pigs. EVLW was measured by thermal-dye dilution technique, by a fibreoptic thermistor catheter system (system 1), and by a thermistor catheter-external optical cuvette system (system 2). During baseline conditions, at which cardiac output was 3.65 l/min, and EVLW was 11.7 and 7.7 ml/kg b.w. with systems 1 and 2 respectively. A reduction of cardiac output to a mean of 1.90 l/min by the addition of halothane to the inspired gas did not significantly affect EVLW with system 1 (-5%) but increased EVLW by 39% (p less than 0.05) with system 2. An increase of cardiac output to a mean of 4.78 l/min by intravenous infusion of isoproterenol caused a small increase in EVLW with system 1 (14%; p less than 0.05) and a decrease with system 2 (10%; p less than 0.05). The dependence on cardiac output was the same whether the catheters were positioned centrally (aortic root) or peripherally (abdominal aorta). With system 1 the CO dependence was due to different time constants in thermistor and optical systems, and with appropriate phasing the dependence could be eliminated. With system 2 a large overestimation of the mean transit time difference between the two indicators was seen when cardiac output was low, resulting in overestimation of EVLW. It is concluded that the dependence of EVLW volume on cardiac output is an artefact due to technical problems in the design of the recording equipment rather than a reflection of pulmonary or vascular effects. PMID- 2332539 TI - Value of C-reactive protein in reflecting the magnitude of complement activation in children undergoing open heart surgery. AB - The kinetics of C-reactive protein (CRP) were studied prospectively in 30 children (aged 21 days - 16 years) undergoing open heart surgery. CRP was related to the kinetics of total haemolytic complement, complement C3a and postoperative complications. Two (7%) patients died and ten (33%) had postoperative complications. The patients with complications were younger (p less than 0.035), underwent longer perfusions (p less than 0.001) and had longer aortic cross clamping times (p less than 0.003). The mean peak CRP level after surgery (108 mg/l) was reached, on the average, in 43 h. No statistical difference in CRP concentrations was found between the complication and non-complication groups. Extensive complement activation was seen in every patient. CRP did not reflect the magnitude of complement activation induced by cardiopulmonary bypass. The patient sample was too small to draw reliable conclusions about the value of CRP in detecting postoperative complications after open heart surgery in children. PMID- 2332540 TI - The effects of norepinephrine infusion on oxygen consumption in a patient with septic shock. AB - A 65-year-old man developed postsurgical septic shock, unresponsive to plasma volume expansion and administration of dopamine and dobutamine. A continuous norepinephrine infusion was then started and the dose increased to 0.62 micrograms.kg-1.min-1 until the mean arterial pressure was 70 mmHg. Prior to and during the norepinephrine infusion, oxygen consumption was continuously measured with a mass spectrometer system. There was a parallel increase in mean arterial pressure and oxygen consumption (+ 35%). There was also an increase in cardiac index and oxygen delivery. Systemic vascular resistance was only transiently increased. In this case with septic shock, norepinephrine infusion improved hemodynamic variables with an associated increase in oxygen consumption. PMID- 2332541 TI - Seizures related to severe hypophosphataemia induced by mechanical ventilation. AB - A patient with chronic obstructive pulmonary disease and acute respiratory failure developed grand mal seizures in the hours following onset of mechanical ventilation. These seizures were associated with an acute increase in arterial pH and were related to the occurrence of acute severe hypophosphataemia associated with recovery from respiratory acidosis. PMID- 2332542 TI - Cardiac index and oxygen consumption during weaning in patients who need inotropic support. PMID- 2332543 TI - Acute diaphragmatic paralysis after chest tube placement. PMID- 2332545 TI - Effect of endotracheal suctioning on arterial blood gases in children. AB - The occurrence of hypoxia during endotracheal tube suctioning and its prevention was examined in 25 hemodynamically stable and non-cyanosed pediatric patients. In each patient 4 suction and treatment protocols were studied: 1. pre- and post suction arterial blood gases (ABG) with no treatment (control). 2. ABG with pre suction oxygenation. 3. ABG with presuction hyperinflation. 4. ABG with postsuction hyperinflation. With no presuction treatment the PO2 and saturation fell significantly after suctioning from control level of 116.6 +/- 9.4 mmHg to 93 +/- 9.3 mmHg post-suction and 97.2 +/- 0.4% to 92.8 +/- 1.4% (p less than 0.001) respectively. In 6 patients with low but adequate pre-suction PO2, hypoxic levels (PO2 less than 60 mmHg) were found post-suction. The significant fall in PO2 was completely prevented by pre-suction oxygenation. Post-suction hyperinflation induced a rapid return of the PO2 to control levels. These results suggest that severe hypoxia might occur during endotracheal suctioning and can be prevented by pre-oxygenation. We recommend 1 min oxygenation with FiO2 1.0 prior to suctioning procedures and intermittent hyperinflation with 100% oxygen during repeated endotracheal suction passes to prevent hypoxia, especially in children in respiratory failure who already have low or borderline pre-suction PO2. PMID- 2332544 TI - Hemodynamic effects of amrinone in children after cardiac surgery. AB - The hemodynamic effects of amrinone were assessed in seven children following cardiac surgery. Amrinone was administered as a bolus of 1 mg kg-1 body wt., followed by continuous infusion at 10 micrograms kg-1 min-1 for 1 h and two stepwise increases to 20 and 40 micrograms kg-1 min-1 for 30 min each. Hemodynamic data were obtained and plasma concentrations of amrinone measured 1 h after the bolus dose and immediately before each increment of the infusion rate. Amrinone levels ranged from 0.7 to 2.3 mg l-1. Administration of amrinone lowered systemic vascular resistance from 20.0 +/- 4.3 to 16.5 +/- 4.6 mmHg l-1 min-1 m-2 (p less than 0.05) and reduced mean arterial pressure from 71.7 +/- 9.5 to 62.6 +/- 13.5 mmHg (p less than 0.05) at the highest infusion rate, confirming the known vasodilative effect of the drug. However, these effects did not result in a statistically significant increase in stroke volume (35.0 +/- 7.5 to 35.5 +/- 7.0 ml m-2, NS) or cardiac index (3.10 +/- 0.50 to 3.20 +/- 0.40 l min-1 m-2). One additional patient, in whom a higher loading dose was tried in order to achieve a higher plasma concentration, developed systemic hypotension. A correlation was established between the plasma concentrations of amrinone and the percentage decrease in systemic resistance (r = 0.70, p less than 0.05). These results suggest that in children after open heart surgery, amrinone acts primarily as a systemic vasodilator, with questionable inotropic effect. Accordingly, its use should be restricted to children with severe cardiac failure and documented highly elevated afterload. PMID- 2332546 TI - The Commonwealth Nurses' Federation: a force for worldwide professional strength. PMID- 2332547 TI - HIV infection and AIDS in England: the experience, knowledge and intentions of community nursing staff. AB - A postal survey of 5243 community nursing staff throughout England sought information about their experience, education, knowledge, confidence and beliefs in relation to the human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS). A response rate of 74% was obtained. While experience of patients positive for HIV antibody or with AIDS was limited, one-third of community nursing staff had encountered patients worried about HIV infection. However, most lacked confidence to provide health education, counselling and terminal care. A quarter felt that they should have the right to refuse to care for patients with AIDS, while 85% were concerned about their lack of experience. In order to play an effective role in the prevention and management of HIV infection, community nursing staff need to be assisted in making links between knowledge they already possess and its application to HIV infection, and in developing and practising skills. PMID- 2332548 TI - How postpartum women explain their lack of obtaining adequate prenatal care. AB - The quality of life for infants and children is often dependent on the adequacy of the prenatal care pregnant women receive. From July through to December 1985, 15% of pregnant women in one Midwestern county were identified as having inadequate prenatal care. The purposes of the study were to identify and analyse the reasons women in that county gave for not obtaining adequate prenatal care. In addition, chi-square was used to determine the relationship between the reasons given and the three variables, age, time between knowledge of pregnancy and making an appointment for care, and source of payment. A convenience sample (n = 44) was used in a study over a 5-month period at three locations. The Health Belief Model was the conceptual framework for this study. Insufficient money to pay for care was the primary reason given for not obtaining adequate prenatal care (81%). Other reasons included motivational issues (45%) and access or lack of transportation (19%). There was a significant relationship (P = 0.05) with four reasons to the variable of age and with three reasons to both the variables of time and source of payment. The following recommendations were identified as a result of this research: the need for subsidized prenatal care and the need for a community-wide education campaign regarding the need for adequate prenatal care and the consequences of inadequate care. Prenatal care is sometimes not available to all in the United States in spite of the relationship of infant mortality and the quality of life for infants and children to adequate prenatal care. PMID- 2332549 TI - Predictors of parental attachment during early parenthood. AB - Parental attachment of 121 high-risk women, 61 partners of high-risk women, 182 low-risk women, and 117 partners of low-risk women, was studied at the first week postpartum and 8 months following birth. The tests of theoretical models showed low predictive ability explaining from zero to 21% of the variance in parental attachment in the four groups over the two test periods. Empirical respecified models predicting parent-infant attachment at the first week postpartum and 8 months explained 31% and 29% of the variance among high-risk women, 69% and 45% among high-risk partners, 41% and 53% among low-risk women, and 35% and 38% among low-risk partners. Parental competence was a major predictor of parental attachment over all test periods for all four groups. Early parent-infant contact following birth was never a predictor except at 8 months when, among low-risk women, the opposite effect than that expected was observed; the later women held their infants the higher was their attachment. High-risk women scored significantly higher than low-risk women during the first week postpartum only. PMID- 2332550 TI - Efficacy of self-care measures for perimenstrual syndrome (PMS). AB - More than 90% of women are affected by one or more of the signs and symptoms of perimenstrual syndrome (PMS), which causes disruptions at work and in family relations and can be economically costly. Self-care measures relating to lifestyle modifications, most particularly nutrition and exercise, can be helpful in preventing and/or alleviating the number and severity of symptoms. This quasi experimental study of a pre-test and post-test design showed a statistically significant increase in self-care measures for PMS with a significant decrease in symptoms, thus impacting on the control of PMS. PMID- 2332551 TI - Health visitors as educators. AB - This paper describes some models of health education as a context for considering data from a recent study of mothers' and health visitors' perspectives on good child health care. Most health visitors favoured an individualistic top-down approach aimed at changing mothers' behaviour. Mothers preferred a dialogue which started from their own priorities. PMID- 2332552 TI - The Neuman System Model applied to mental health nursing of older adults. AB - As we move into the 21st century, nurses are facing the challenge of contributing to the health care of a society with an increasing proportion of ageing persons. This group of people become more heterogeneous as they age, bringing with them an extended life history of experiences of wellness and illness. They have been faced with numerous stressors and losses and have made successful or unsuccessful adaptation to those life experiences. One of the disconcerting stressors of the elderly is the promotion and maintenance of mental health. In this paper we will examine the application of the Neuman System Model to the mental health nursing of older adults. PMID- 2332553 TI - Timing of preoperative patient teaching. AB - With the increasing cost of health care and the growing constraints made by third party payers, in-hospital time for preoperative teaching is quickly being reduced. Seventy-two patients attended preoperative instruction either as an inpatient the day before surgery or as an outpatient 4-8 days before surgery. Anxiety and knowledge levels were measured before and after class and the evening before surgery. No differences were found between the groups on a measure of anxiety levels. Both groups demonstrated a moderate anxiety level with no significant change over the testing period. Using the knowledge pretest as a covariate, repeated measures analysis of variance suggested the knowledge gained with the class was significantly greater for the outpatient group than the inpatient group (P = 0.018). There was also a significant positive relationship between the knowledge score and knowing someone who had cardiac surgery (t = 2.34, d.f. = 66, P = 0.022). The results suggest that it makes little difference whether patients receive information up to a week before surgery or just the day before; therefore, the more economical preadmission teaching may be the path of choice. PMID- 2332554 TI - Research on nurse-patient relationships: problems of theory, problems of practice. AB - Research, theoretical and educational literature on interpersonal relations between nurses and patients has proliferated since the 1960s. This has generated a range of divergent accounts of what the nurse-patient relationship (NPR) ought to be; how this should be achieved; and how the NPR is constituted in practice. In this paper--through a selective review of the literature--the development of two contending perspectives on NPR and on nurse-patient interaction (NPI) characterized as technocratic and contextual, is discussed, and related to the increasingly problematic status of the relationship between nurses and patients in nursing theory and research. PMID- 2332555 TI - Programme evaluation in nursing education: the state of the art. AB - Programme evaluation is a complex but integral component of a nursing education programme. It is an ongoing process of collecting and describing data which provides the basis for decision making. Specifically, evaluative data can be used to prepare for accreditation visits; account for budgetary expenditures; answer requests for information; develop faculty and staff; and examine the planned and actual effects of the programme within the community and make changes accordingly. There are several programme evaluation models available to guide the evaluation process, but no single model is best and nurse educators must consider a variety of variables. Ideally, the selection of a model should be based on the purpose of the evaluation, programme needs, material and spatial resources, and personnel time, as well as the needs and desires of key interest groups. Several considerations are also required before the model is implemented. These include determining specific priorities for evaluation since all aspects of a programme (conceptual framework, philosophy, programme goals, student characteristics, graduates' performance, faculty and administrative expertise, as well as adequacy of resources) usually cannot be evaluated simultaneously; how the evaluation should proceed; time frames for specific evaluation projects; and personnel responsible for the evaluative activities. PMID- 2332556 TI - Moral learning in nursing education: a discussion of the usefulness of cognitive developmental and social learning theories. AB - The preparation of students for ethically sound practice is an essential concern for nurse educators. The theories of cognitive development and social learning theory are discussed as explanations of moral learning. The implications of the application of each of these theories to nursing education are discussed and the usefulness of each theory to nurse educators is reviewed. It is argued that neither theory is entirely satisfactory for application to nursing education and it is concluded that a pragmatic eclecticism is desirable in the approach to moral education in nursing. PMID- 2332557 TI - A systematic comparison of feedback and staff discussion in changing the ward atmosphere. AB - The efficacy of therapeutic programmes depends on several characteristics of the treatment environment. For this reason therapists are increasingly directing their efforts towards changing the social characteristics of treatment units. This study aimed to promote change in social climate by providing nursing staff with structured information about their unit. The 'real' and 'ideal' social climate of the unit was defined and assessed using the Ward Atmosphere Scale. All staff were asked to complete it during an assessment period. Feedback about their perception of the unit was provided to staff in two ways. One group of staff received written feedback only; a second group received in addition the opportunity to discuss the feedback and strategies for reducing the real-ideal discrepancies in four once-monthly meetings. The effect of the feedback on the social climate of the unit was ascertained by further assessment using the WAS and from interviews with all staff. The evaluation suggested that the feedback had contributed to changes in several procedures in the unit and to a reduction in the real-ideal discrepancies for the systems maintenance elements. The effect was greater for the group of staff who had the opportunity to discuss the feedback in a formal setting. PMID- 2332558 TI - Effecting personal effectiveness: assertiveness training for nurses. AB - This paper describes a client-centred approach to assertiveness training with nurses. The approach recognizes and utilizes the skills and resources within a group, through a process of enabling rather than teaching. The group's own knowledge and experiences are shown to be at least as valid as other academic and research texts which are referred to. In personal development terms they are more valid. Technique-based courses are thought to have less impact than this approach, clearly rooted in self-awareness and development. After looking at the history of assertiveness training, and ways of defining it, the paper goes on to describe the process and content of a programme which is group led. Space is also given to considering why it may be particularly difficult for nurses to act assertively, due to tradition and stereotypes. PMID- 2332559 TI - Helping people to stop smoking: a study of the nurse's role. AB - Sixteen trained nurses from various clinical backgrounds participated in a project designed to describe the process and assess the outcome of their attempts to help a range of patients and clients to stop smoking. A case-study approach was employed and the nurses initiated 68 health education interventions related to smoking cessation. All interventions were tape-recorded and data on patients' and clients' characteristics, smoking history, health beliefs and motivation to give up smoking were also collected. Forty-two patients were followed up 1 year post-intervention. Data collected at this time revealed that 17% had successfully given up smoking, while a further 12% had substantially reduced their cigarette consumption. These findings compare very favourably with those of previous studies in which general practitioners have attempted to help patients stop smoking. The results of the research reported here therefore suggest that nurses have enormous potential for fulfilling a highly effective health education function. PMID- 2332560 TI - Lifestyle modification as an intervention for inner city women at high risk for preterm birth. AB - This study details a programme which emphasized nursing interventions for women at high risk for preterm birth. Preterm birth continues to be a major health problem, with ongoing research being conducted both in the United States and internationally in an effort to find causative factors. Programmes designed to prevent preterm birth have been described often in the literature, with lifestyle factors being implicated in the incidence of preterm birth by many researchers. The purpose of this study was to determine the lifestyle factors most often associated with preterm birth in a high risk population of inner city women, and to examine the effect of change in lifestyle when change was possible. Women at high risk for preterm birth were interviewed extensively for prevalence of 12 lifestyle factors most often cited in the literature as being associated with preterm birth. Counselling and education were offered to each woman, with emphasis on symptom recognition and modification of lifestyle activities. Comprehensive prenatal care was administered by programme personnel. A profile of the women's reported lifestyle activities and stress factors is presented along with the relationship to outcome. The data suggested that, when change in lifestyle activity or stress was possible, women who decreased the activity or stressor were more likely to deliver at term. This study represents one of the first efforts in the United States to produce a prospective database to quantify risk and analyse the impact of change in activities associated with symptoms of preterm labour in high risk women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332561 TI - Predictors of nursing staff turnover. AB - Nursing turnover is of great concern to patients, management and the profession, and numerous studies have been conducted to increase understanding about this phenomenon. Most of these, however, have focused on staff nurses in the public sector; little is known about nurse manager turnover or the characteristics of nurses leaving the private hospital sector. The purpose of this study was to examine turnover of staff nurses and nurse managers in both the public and private hospital sectors. Variables which appeared to have a consistent relationship with nurse turnover were identified from the literature, and multiple regression methods were used to attempt to identify variables which could be used to predict turnover behaviour of staff nurses and nurse managers. This study encountered methodological difficulties similar to those which have plagued previous studies; nevertheless, a clearer picture of nursing turnover is emerging. PMID- 2332562 TI - Albumin, bradykinins, and eosinophil cationic protein on the nasal mucosal surface in patients with hay fever during natural allergen exposure. AB - This study examined plasma- and eosinophil-derived products in nasal lavage fluids obtained from patients with hay fever during natural allergen exposure. Nine patients with strictly seasonal allergic rhinitis and five normal, nonallergic subjects (control group) were studied. Nasal lavages were performed twice weekly, starting 1 week before the expected birch-pollen season and continuing for 6 weeks, thereby covering the entire birch-pollen season. Nasal symptoms and pollen counts were recorded daily. The lavage fluid was analyzed for it content of albumin, bradykinins, and eosinophil cationic protein (ECP). During the pollen season, each of these solutes was significantly increased in the nasal lavage fluid from the allergic patients (p less than 0.05) but not from the control subjects. Albumin, bradykinins, and ECP generally correlated better between themselves than with symptoms and pollen counts. We conclude that natural exposure to allergens induces plasma exudation and increased levels of ECP on the human nasal mucosa. PMID- 2332563 TI - Late asthmatic reactions to occupational sensitizing agents: frequency of changes in nonspecific bronchial responsiveness and of response to inhaled beta 2 adrenergic agent. AB - Late asthmatic reactions have been demonstrated, generally, to increase bronchial responsiveness and are believed to respond poorly to inhaled bronchodilator. To assess the frequency of changes in bronchial responsiveness, we reviewed the records of 101 subjects with late asthmatic reactions and of 63 subjects with isolated immediate reactions after specific inhalation challenges to various occupational agents. These subjects had undergone nonspecific inhalation challenges to histamine or methacholine on a control day and after the late reaction when FEV1 had returned to +/- 10% baseline. We also reviewed 99 cases of subjects with late reactions who were administered an inhaled beta 2-agent (albuterol, 200 micrograms) during the late reaction. Fifty-seven/101 (56%) subjects with late reactions and 24/63 (38%) subjects with isolated immediate reactions demonstrated a twofold or greater change in provocative concentration of histamine or methacholine causing a 20% change in FEV1 (PC20) from baseline (p = 0.02; odds for the presence of significant changes in PC20 in subjects with late reactions, 56%; odds for the absence of significant changes in PC20 in subjects with immediate reactions, 62%). Changes in FEV1 greater than 20% after administering albuterol at the time of the late reactions occurred in 78% of the subjects tested; in 66%, FEV1 returned to greater than 90% baseline. This retrospective study demonstrates that changes in bronchial responsiveness after late reactions are not constant and do not appear to distinguish satisfactorily late from immediate reactions. Furthermore, late reactions respond well to beta 2 agonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332564 TI - A study of the mechanism of the antiasthmatic action of inhaled budesonide. AB - Inhaled antiasthmatic steroids have been assumed and yet never proved to exert their antiasthmatic effect by topical action in the airways. We tested the hypothesis that the efficacy of inhaled budesonide (BUD) might be due instead to its systemic activity after absorption. We compared inhaled and oral BUD with doses selected to ensure higher peak plasma levels and a greater area under the plasma concentration curve with the oral treatment. After pretreatment with beclomethasone to maximize asthma control, 47 adults with asthma were randomized to receive 0.4 mg of inhaled BUD per day (n = 16) or 1.4 mg of oral BUD per day (n = 15), or placebo (n = 16) in double-blind fashion and then followed weekly until asthma relapsed or for 8 weeks if no relapse occurred. "Relapse" was defined as a drop in the mean peak expiratory flow rate greater than 2 SEM below the mean during the baseline week before switching to the test drugs. The time to relapse was the primary outcome variable. Time to relapse was longer with inhaled than with oral BUD (medians, 22 versus 7.9 days; p = 0.003) or placebo (medians, 22 versus 9 days; p = 0.004). Oral BUD and placebo did not differ (p = 0.41). The morning serum cortisol levels remained normal during all three treatments. Thus, at conventional dosage the antiasthmatic effect of inhaled BUD may be fully explained by a local intrapulmonary action. PMID- 2332565 TI - Effect of inhaled furosemide on the bronchial response to methacholine and cold air hyperventilation challenges. AB - Inhaled furosemide has been recently demonstrated to inhibit the bronchoconstrictive effects of exercise, ultrasonically nebulized distilled water, and antigen challenge. The presumed mechanism of action of these challenges is through mast cell degranulation. We report on the effect of inhaled furosemide on cold-air hyperventilation challenge (CAHC) and methacholine challenge. We studied 10 subjects with mild to moderate asthma in a double-blind, placebo-controlled, crossover study. Inhaled furosemide did not affect FEV1 in the hour after inhalation, and there was no significant difference between placebo or furosemide on the dose of methacholine causing a 20% fall in FEV1. Our results demonstrated inhaled furosemide significantly attenuated the bronchoconstrictive effect at 6 and 9 minutes after CAHC (p less than 0.05 and 0.029, respectively) when furosemide was compared to placebo and approached significance at 12 and 15 minutes after CAHC (p = 0.052 and 0.56, respectively). Inhaled furosemide attenuates CAHC but does not effect methacholine-induced bronchoconstriction. PMID- 2332566 TI - Safety of 1 year of treatment with budesonide in young children with asthma. AB - Inhaled budesonide has been demonstrated to be effective and safe when it is used in the prophylaxis of severe asthma in adults and school-age children but has not been studied in younger patients with asthma. Sixteen children, aged 3 1/2 to 7 years, with severe asthma, were treated with budesonide aerosol, 200 micrograms daily, via a spacer for 1 year in an open study. One month after starting budesonide therapy, a significant decrease in the number of days with asthmatic symptomatology, mean symptom scores, use of concomitant antiasthmatic medications, and increase in the peak expiratory flow rates were observed compared with the 1 month run-in period. This improvement was maintained throughout the year with budesonide therapy. During the study period, the height and weight of the children were not significantly deviated from the expected, and their bone age advanced normally. Adrenal function, as evaluated by fasting 8 AM blood cortisol levels and after adrenocorticotropic hormone stimulation, demonstrated no adverse effects with budesonide therapy. The suspectibility to severe infections was low, as evidenced by infrequent use of antibiotics. We conclude that a 12-month administration of inhaled budesonide to preschool-age children is safe and efficient and can be useful in the management of severe asthma in this young age group. PMID- 2332567 TI - Comparison of different extraction methods of Alternaria allergens. AB - Spore and mycelial allergens of two species of Alternaria (A. brassicicola and A. alternata) extracted under two different conditions were analyzed by radiorocket immunoelectrophoresis, crossed radioimmunoelectrophoresis, and Western blotting with a pool of sera from Alternaria-allergic patients. More allergens were extracted after disruption of the cells if protease inhibitors and a phenol binding component were included in the homogenization buffer. However, the 31 kDa major allergen was extracted in about the same amount, either by incubation or by cell breakage of the cells. This 31 kDa allergen was present in higher concentration in the mycelium than in the spore. The difference between the two species studied is less than between spore and mycelium from the same species. PMID- 2332568 TI - Response to a Haemophilus influenzae type b diphtheria CRM197 conjugate vaccine in children with a defect of antibody production to Haemophilus influenzae type b polysaccharide. AB - A defect in antibody response to immunization with Haemophilus influenzae type b (Hib) capsular polysaccharide vaccine has been reported in children with recurrent infections and normal immunoglobin levels. We identified 15 children, aged 2 to 6 years, with this defect, and we evaluated their response to immunization with an Hib capsular oligosaccharide diphtheria CRM197 protein conjugate vaccine (HbOC). The children received a series of three vaccines: HbOC at 0 and 8 weeks, and the Hib polysaccharide vaccine at 16 weeks. Levels of antibody to the Hib capsular polysaccharide (polyribosyl ribitol phosphate, PRP) and to diphtheria toxoid were obtained before and 4 weeks after each vaccination. The geometric mean serum anti-PRP concentration was 0.17 microgram/ml before immunization and 29.3 micrograms/ml after the second HbOC immunization (week 12). All 15 children had postvaccination anti-PRP antibody levels greater than 1.0 microgram/ml after receiving the second HbOC (week 12). In addition, booster responses were observed after the second Hib conjugate in 13 of the patients and after the Hib polysaccharide in four of the patients. All patients with low preimmunization diphtheria titers had a response to the diphtheria toxoid. These results suggest that conjugation of Hib polysaccharide with diphtheria CRM197 overcomes the defective antibody response to Hib oligosaccharide in children who are initially observed with recurrent infections and inability to respond to the Hib polysaccharide vaccine. PMID- 2332569 TI - Evaluation of ocular hypersensitivity to dipivalyl epinephrine by component eye drop testing. AB - Dipivalyl epinephrine (dipivefrin) is a prodrug of epinephrine used for topical glaucoma therapy. Local side effects have been noted in approximately 20% of patients treated and include conjunctival hyperemia, foreign body sensation, and follicular conjunctivitis. We studied five patients with adverse local reactions to dipivefrin (Propine) eye drops. Propine contains the following: dipivefrin, 0.1%; mannitol, 1.89%; sodium metabisulfite, 0.075%; disodium edetate, 0.0127%; and benzalkonium chloride, 0.004%. Since the reactions could conceivably have been caused by an ingredient other than dipivefrin, we first patch tested the patients with the maximum recommended concentration of each ingredient. All patch tests were negative. Sterile ophthalmic solutions of each individual component at the concentrations used in the commercial product were then prepared. In a double blinded study, the patients applied two drops of each preparation, twice daily for 1 week, with a 1-week, drug-free period between trials. Dipivefrin alone reproduced each patient's initial Propine-induced conjunctivitis; symptoms occurred unilaterally in one patient and bilaterally in the other four patients. This study indicates that testing with single component eye drops can identify the provocative component in ocular drug hypersensitivity and that these reactions can be unilateral. PMID- 2332570 TI - The mental efficiency of the elderly person with type II diabetes mellitus. AB - Cognitive function is often impaired in type I diabetes mellitus, especially when onset is in early childhood. Limited evidence suggests similar impairment in the much larger population of older persons with type II diabetes. We report here the results of 13 measures of mental efficiency in persons between 65 and 77 years of age without gross mental impairment. Nineteen persons with type II diabetes were compared with 19 controls with normal glycosylated hemoglobin values and to seven persons not previously known to have diabetes but who had elevated glycosylated hemoglobin. Significant differences (P less than .05) between the nondiabetic control and diabetic groups were noted on eight of the 13 tests. The group of subjects with elevated glycosylated hemoglobins showed levels of cognitive performance intermediate between the normal and known diabetic groups on the majority of tests. These findings confirm that mental efficiency is frequently impaired in older persons with diabetes. Given the high prevalence of diabetes in the aging population we suggest that diabetes may be another important factor contributing to premature loss of cognitive abilities in older people. PMID- 2332571 TI - Effects of self-monitoring of blood glucose on quality of life in elderly diabetic patients. AB - Self-monitoring of blood glucose (SMBG) has been associated with improvement in diabetes knowledge and glycemic control in young and middle-aged diabetic patients. This study investigated the influences of SMBG on the quality of life in 20 older diabetic individuals, aged 60 to 79 years with duration of diabetes 15.6 +/- 2.3 (SD) years. Questionnaires (Cronbach's alpha reliability = .93) were administered regarding the impact of four aspects of diabetic self-care--general factors, diet, medications, and monitoring blood or urine--on quality of life. Each category was scored separately. Data were analyzed comparing individuals using SMBG with those monitoring glycosuria. Older patients showed acceptance of SMBG with respect to performance, lack of time consumption, ease of record keeping, and less embarrassment. Individuals performing SMBG reported better medication compliance than those monitoring glycosuria. No differences were observed between the two groups for general factors, diet, or the overall perception of quality of life. Both groups of patients reported that diabetes and performing self-care techniques did not significantly interfere with their life style. In conclusion, this study demonstrates that self-care techniques, such as SMBG, do not negatively influence the perception of quality of life in older people. PMID- 2332572 TI - Deciding to restrain medical patients. AB - To determine when and why patients are placed in mechanical restraints, we surveyed the nurse and physician caring for each of 102 restrained patients from the general medical floors of an acute-care hospital. Ninety-three percent of the questionnaires were completed. Nursing questionnaires indicated that over half of patients were restrained during the evening shift. Nurses initiated the use of restraints in 75% of cases. Fifteen percent of the patients' physicians were unaware that the patient had been restrained. In the majority of cases, the nurse and physician believed that restraint was the best alternative for managing the patient although more physicians (11%) than nurses (2%) thought an alternative intervention would be better (P less than .02). As a group, physicians and nurses restrained patients for similar reasons, most often to prevent falls from bed (69%) or to protect medical devices (36%). However, there was poor agreement between the nurse and physician as to the reason for restraint in an individual patient (kappa statistic range from .02 to .43). These findings suggest that nurse and physician communication regarding restraint is poor. We recommend that acute-care hospitals adopt policies to promote communication between nurses and physicians concerning restraints to ensure that use of this potentially hazardous intervention is used only when necessary. PMID- 2332573 TI - Nutritional intake, socioeconomic conditions, and health status in a large elderly population. AB - The nutritional intake of a large population of noninstitutionalized older people living in an urban area was studied in relation to socioeconomic conditions (living environment, income, and education) and health status (affective, functional, and physical health) to identify the subgroups at risk for malnutrition. Twenty-four-hour dietary recall was used to determine the percentage of older subjects with dietary intake of specific nutrients below two thirds of the 1980 Recommended Dietary Allowances. Ninety percent of the older people examined showed inadequate intake of thiamine and vitamin B6, and 30% to 40% demonstrated deficiencies of vitamin A, vitamin C, niacin, vitamin B12, calcium, and iron; only 10% of subjects had inadequate intake of protein. Poor nutritional intake was correlated more strongly with socioeconomic conditions, functional level, and affective status than with physical health status. PMID- 2332574 TI - Survival in acute leukemia in elderly patients. No improvement in the 1980s. AB - Acute leukemia is more common in older people than in the young or middle-aged. However, the possibilities of achieving remission or prolonging survival are both inversely correlated with increasing age. We studied survival in 118 acute leukemia patients over the age of 64 seen at a university hospital from 1970 to 1987. Seventy percent had myeloid morphology. Median survival times were 106 days in those diagnosed in the 1970s and 71 days for those diagnosed in the 1980s. This was little changed from an earlier series from the same hospital extending back to the 1940s in which median survival was 69 days. Considering the two decades separately, age at diagnosis, sex, race, type of leukemia, and whether or not disease-specific treatment was applied had no significant effect on survival duration. Acute leukemia in the older patient demands difficult medical and ethical choices. Supportive therapy provides immediate comfort and relatively limited morbidity with certainty of death within a few months. Disease-specific therapy causes immediate morbidity for all, shortened life for the majority, and extended life for the minority. PMID- 2332575 TI - Salmonella outbreak in a nursing home. AB - We performed a retrospective review of an outbreak of Salmonella gastroenteritis that occurred in a community nursing home in 1987. Forty-four of 199 residents had a diarrheal illness; Salmonella heidelberg was isolated from the stool in 19 cases. Although the distribution of cases suggested a common source for the outbreak, no common source of infection could be demonstrated, despite extensive investigation. The clinical presentation of symptomatic individuals ranged from mild diarrhea to a severe gastrointestinal illness, and 26% of symptomatic, culture-positive patients required hospitalization. The median duration of pathogen excretion during convalescence in untreated residents was six weeks, but six patients who were treated with antibiotics shed S. heidelberg for a median duration of 14.5 weeks. We conclude that (1) the clinical spectrum of Salmonella gastroenteritis in nursing-home patients is variable, ranging from mild to severe illness; and (2) nursing-home Salmonella outbreaks impose a high economic burden because of expense of epidemiologic investigation, prolonged isolation measures, hospitalization for severely ill residents, and potential institutional closure. PMID- 2332576 TI - A questionnaire investigation of anxiety and depression in early dementia. AB - We report findings on a study of anxiety and depression by questionnaire in 50 patients with mild dementia and 134 control subjects using the Hospital Anxiety and Depression Scale. Thirty-eight percent of patients and 9% of controls had a possible or probable diagnosis of an anxiety disorder. Possible or probable depression was found in 28% of the patients and 3% of the controls. These rates for the patients were above those in normal populations. All patients and control subjects were tested with the Extended Scale for Dementia (ESD). Neither group showed a significant relationship between depression and ESD scores. In the control subjects there was a negative correlation (P less than .006) between anxiety and cognitive scores, one that was not found in the patients. PMID- 2332577 TI - Late-onset asthma in a demented elderly patient. The value of methacholine challenge in diagnosis. PMID- 2332579 TI - Reconciling autonomy and the value of life. PMID- 2332578 TI - Cruzan v Harmon, and In the Matter of O'Connor. Two anomalies. AB - Two recent court cases, Cruzan v Harmon and In the Matter of O'Connor, denied family requests to withhold or withdraw life-sustaining treatment. The facts of the cases are discussed, as well as the impact on medical practice for physicians in Missouri and New York. Approaches of other state courts are pointed out. While critical of the judicial reasoning in both cases, the article provides guidance to doctors about how to work within the court decisions and still honor patient wishes. PMID- 2332580 TI - Psychosocial aspects of diabetes mellitus in older persons. PMID- 2332581 TI - The hazards of multidisciplinary care. PMID- 2332582 TI - Developmental changes in hepatic copper proteins in the guinea pig. AB - We have suggested that Wilson's disease is caused by failure to adapt from the fetal to adult mode of copper metabolism and that the study of liver copper ontogeny might provide clues to the pathogenesis of Wilson's disease. This study traces the developmental changes in hepatic copper binding proteins in the guinea pig. During the last trimester, as fetal hepatic copper increases, metallothionein is the major copper binding peak in both the soluble and particulate supernatant fractions. After birth this peak decreases in parallel with the fall in liver copper. Metallothionein is absent from adult soluble supernatant and copper is associated with superoxide dismutase and a high molecular weight protein. A novel low molecular weight copper binding component is present in the particulate supernatant of neonatal liver, but is absent from the adult. Unlike many other animals, but similar to man, the switch from the fetal to adult mode of copper metabolism occurs at birth. Comparison of the copper protein profiles of the fetus and neonate with Wilson's disease are required to test the hypothesis that Wilson's disease is caused by developmental arrest of copper ontogeny. PMID- 2332583 TI - Evidence that plasma membrane fluidity of isolated hepatocytes is modified by exposure to microtubule-depolymerizing drugs. AB - The role of microtubules on membrane fluidity has been investigated on freshly isolated whole rat hepatocytes prepared by the perfusion method and exposed either to the microtubule-depolymerizing drugs colchicine and vincristine or to beta-lumicolchicine, a colchicine analog deprived of biological activity. Exposure of hepatocytes to 6.3 microM colchicine or to 3.0 microM vincristine led to a significant decrease of membrane fluidity as measured by fluorescence polarization of trimethylammoniodiphenylhexatriene (TMA-DPH). No changes were observed in cells exposed to 10.0 microM beta-lumicolchicine. These observations support the hypothesis that the microtubular system plays a role in the modulations of physico-chemical properties of the plasma membrane. PMID- 2332584 TI - Use of quantitative liver function tests--caffeine clearance and galactose elimination capacity--after orthotopic liver transplantation. AB - To establish the potential value of quantitative tests of liver function following orthotopic liver transplantation (OLT), a total of 100 determinations of caffeine clearance (CafCl) and galactose elimination capacity (GEC) were made in ten OLT recipients early in the post-operative course (days 2, 4, 6, 8 and 12) and later when clinically stable (3-12 months). Values were compared with a reference range in six normal volunteers in whom it was shown that the standard doses of caffeine (125 mg) and galactose (0.5 g per kg body weight) could be given together without interference. In orthotopic liver transplantation recipients initial GEC and CafCl measurements showed no correlation with peri operative blood loss, donor ischaemia time, initial bile flow or survival. Throughout the early post-operative period, there were wide inter- and intra individual variations in both CafCl (17-fold range from 0.16 to 2.7 ml.min-1.kg 1) and GEC (2.4-fold range from 5.1 to 12 mg.min-1.kg-1), but the only correlation of test values with standard liver function tests results was between GEC and gamma-glutamyltranspeptidase. However, GEC values fell by 19% during periods of acute rejection and there was an inverse correlation of GEC with white cell count probably related to sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332585 TI - Spontaneous regression of oesophageal varices after long-term conservative treatment. Retrospective study in 20 patients with alcoholic liver cirrhosis, posthepatitic cirrhosis and haemochromatosis with cirrhosis. AB - Spontaneous regression of oesophageal varices in liver cirrhotics without sclerotherapy or shunt operation has only been known in alcoholic cirrhosis after alcohol abstinence. Therefore, 20 liver cirrhotics of different aetiologies were controlled over 13 years (six alcohol, nine hepatitis, five haemochromatosis). Under strict alcohol abstinence, all underwent treatment with lactulose and ammonia-reducing amino acids to improve the urea synthesis in the liver. Since gastrointestinal bleeding was not observed, neither sclerotherapy nor shunt operation were performed. Initially, all patients had oesophageal varices (nine stage III, three stage II-III, eight stage II). Following conservative therapy, eight cirrhotics showed total regression and twelve showed stage I-II. Their Child-Pugh index, and urea synthesis rate improved significantly. Possible causes for the spontaneous regression of oesophageal varices are strict abstinence from alcohol, spontaneous seroconversion in six posthepatic B-cirrhoses and consequent phlebotomy in haemochromatosis. PMID- 2332586 TI - Submaximal oxygen consumption in liver cirrhosis. Evidence of severe functional aerobic impairment. AB - We studied maximal aerobic work capacity in 24 cirrhotic patients whose clinical condition was well compensated. Nineteen of our patients had no heart or lung disease, and five had mild mechanical ventilatory impairment. The patients performed incremental exercise on a treadmill until subjective exhaustion. The maximal exercise levels reached by all were relatively low and led to a lower observed maximal oxygen uptake (VO2 max), than predicted uptake (19.6 +/- 0.5 vs. 37.9 +/- 0.6 ml/kg; p less than 0.001). Observed VO2 max values correlated strongly with the Pugh score, which reflects the degree of liver failure (r = 0.571; p less than 0.01). Since there were no clear cardiac or pulmonary causes to explain the decrease in work capacity, these observations suggest that liver cirrhosis might induce or be accompanied by muscular impairment. VO2 max, which seems to decline with the functional severity of the disease, may be a useful index for evaluating the capacity of patients for physical rehabilitation. PMID- 2332587 TI - Amphotericin B-induced depression in the phagocytic function of the isolated rat liver and its prevention by nifedipine. AB - We investigated the effects of the antimycotic agent amphotericin B (AmB) on the phagocytic activity of the isolated perfused rat liver. At a concentration of 5 microM, the drug markedly reduced the clearance of latex beads by the liver as compared to control preparations. Scanning electron microscopy observations showed that latex beads were attached only to Kupffer cells. A liver scan performed infusing 99Tc-colloidal albumin showed that AmB depressed the uptake of the colloid in all hepatic lobes, with no focal defects. Both in control and AmB experiments no trypan blue uptake occurred. The pretreatment of the perfused liver with the calcium antagonist nifedipine prevented the decrease in phagocytosis induced by AmB. In addition, AmB had no effect on livers perfused with a Ca2(+)-free medium. A decrease in the phagocytic capacity of the perfused liver was also observed after the administration of the Ca2(+)-ionophore A23187. The observations suggest that AmB may exert an intrinsic toxicity on the Kupffer cells, which is, at least in part, responsible for the decrease in phagocytosis induced by the drug. This effect may be of relevance to clinical situations and deserves careful consideration. PMID- 2332588 TI - Difference in the effects of ursodeoxycholate and its taurine conjugate on the biliary excretion of sulfobromophthalein in the rat. AB - A simultaneous intravenous infusion of sulfobromophthalein (BSP) (0.3 mg.min 1.100 g-1) and ursodeoxycholate (UDC) or tauroursodeoxycholate (TUDC) (1.2 mumol.min-1.100 g-1) caused a significantly higher excretion rate of BSP than in the control value without bile salt infusion. In UDC-infused rats, however, the BSP excretion rate began to fall rapidly within the first 30 min of infusion, while the bile flow rate remained high, or even continued to increase. In contrast, the BSP excretion rate in TUDC-infused rats was stable up to 60 min and then began to decline in parallel with the fall of bile flow rate. A significant increase in the BSP transport maximum (Tm) induced by UDC and TUDC in rats does not agree with a previous observation in hamsters where neither of these bile salts enhanced BSP Tm. The discrepancy between these two studies can best be explained by the poor biliary excretion of either TUDC or UDC in hamsters as was previously reported. It was concluded that in rats both TUDC and UDC can significantly increase BSP Tm, which paralleled the excretion rate of bile salts and not the bile flow rate. PMID- 2332590 TI - Presence of HBV-DNA in peripheral blood mononuclear cells from anti-HIV symptomless carriers. AB - The presence of hepatitis B virus DNA (HBV-DNA) in the peripheral blood mononuclear cells (PBMC) of 29 anti-HIV symptomless carriers (eleven HBeAg positive, eleven anti-HBe positive and seven HBsAg negative) and of 40 anti-human immunodeficiency virus (HIV)-negative patients (15 HBeAg positive, 15 anti-HBe positive and ten HBsAg negative) has been studied by dot-blot and Southern blot hybridization. HBV-DNA has been found in similar proportions in both anti-HIV positive and negative patients (36% and 46%, respectively, in the HBeAg positive group and 27% and 37% in the anti-HBe positive group). No HBV-DNA was detected in the PBMC of the HBsAg-negative patients. No relation has been observed between the presence of HBV-DNA in the PBMC of the anti-HIV-positive patients and the detection of HIV antigen (HIV Ag), number of CD4 cells or the CD4/CD8 ratio. In summary, the presence of HBV-DNA in the PBMC of anti-HIV symptomless carriers does not seem to imply that the patient's clinical state has worsened. PMID- 2332589 TI - Detection of hepatitis B virus transcripts in patients with chronic liver disease. AB - Hepatitis B virus (HBV) transcription was studied by Northern blot analysis on total cellular RNA purified from liver biopsies in 70 patients with chronic liver disease (24 HBsAg positive, 15 antiHBs and/or antiHBc positive, 31 HBV negative). No transcripts were found in the HBV negative and in the antiHBs and/or antiHBc positive patients. In the others, three major RNA species were identified: i. a 3.5 kb transcript corresponding to the RNA pregenome; ii. 2.4-2.1 kb transcript corresponding to the s and preS1 gene RNA; iii. lower molecular weight species. All three forms were present simultaneously only in patients with active viral replication, with a strict relation between the presence of the 3.5 kb RNA in the liver and serum HBV-DNA. In conclusion, Northern blot analysis can easily be performed to study viral replication and it can contribute to a better understanding of the molecular processes underlying HBV infection and leading to liver disease in man. PMID- 2332591 TI - Effect of oral propranolol on circulating catecholamines in cirrhosis: relationship to severity of liver disease and splanchnic haemodynamics. AB - Patients with cirrhosis, especially those with decompensated disease have enhanced sympathetic nervous activity. We have investigated the effect of a single oral dose of 80 mg propranolol on circulating catecholamines and related the effect to splanchnic and systemic haemodynamics in 22 patients with cirrhosis. Plasma noradrenaline (NA) was significantly above normal average (NA: 0.52 vs. 0.23 ng/ml, p less than 0.01) and increased with the severity of the liver disease (p less than 0.01). NA was negatively correlated with liver function as estimated by ICG clearance (r = -0.74, p less than 0.01). Azygos blood flow was increased (0.75 l/min) and positively related to plasma NA (r = 0.57, p = 0.05, n = 12). After propranolol intake, plasma NA increased from 0.52 to 0.59 ng/ml (p less than 0.01). This response was found in all Child-Turcotte classes (A: 0.37 to 0.43; B: 0.49 to 0.56; C: 0.78 to 0.88 ng/ml), and in patients with as well as without ascites. Plasma adrenaline increased in the same way (p less than 0.01). Hepatic blood flow (from 1.10 to 0.93 l/min, p less than 0.01) and azygos blood flow (from 0.75 to 0.55 l/min, n = 9, p less than 0.05) decreased significantly after oral propranolol. A borderline significant correlation was observed between the decrease in azygos blood flow and the increase in NA (r = 0.64, p = 0.06). Our results suggest that besides a relationship to liver function and severity of disease, sympathetic nervous activity, as reflected by circulating NA, will further enhance during beta adrenergic blockade, probably by a compensatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332592 TI - Uptake and processing of glycoproteins by isolated rat hepatic endothelial and Kupffer cells. AB - Mannose-(Man) and N-acetylglucosamine- (GlcNAc)-terminated glycoproteins are cleared from blood by carbohydrate-specific receptors present on both hepatic endothelial and Kupffer cells. It is not known whether the same receptors are present on each cell type or the relative contributions to glycoprotein metabolism made by Kupffer and endothelial cells. Here we report experiments where data from glycoprotein metabolism by purified populations of isolated rat hepatic endothelial and Kupffer cells have been analyzed by mathematical modelling and parameter estimation. Kupffer cells had significantly higher binding rate constants (k'21) than endothelial cells for agalactoorosomucoid (AGOR) and hyaluronidase, but lower k12 ('off-rate') indicating that Kupffer cells had higher affinities for Man/GlcNAc-terminated glycoproteins than endothelial receptors. Furthermore, although endothelial cells had similar affinities (k'21 and k12) for AGOR and hyaluronidase, the 'off-rate' of Kupffer cells was significantly greater for AGOR than for hyaluronidase, indicating that Kupffer cell receptors have lower affinity for AGOR. Internalization and ligand catabolic rates also differed between the two cell types. The data indicate that Kupffer and endothelial cells appear to have different Man/GlcNAc receptors and that the destination of a glycoprotein and its subsequent processing is determined by the structure of a glycoprotein's oligosaccharide. PMID- 2332593 TI - Coagulation disturbances following ascites recirculation. AB - To investigate the effects of extra-corporeal ascites recirculation on coagulation, several coagulation variables were measured in ascitic return fluid and plasma before, during and after this procedure in 16 patients with diuretic resistant ascites. Small but significant reductions in plasma fibrinogen levels and platelet counts and increases in plasma X-oligomer were observed during and after the procedure compared with before. These findings are consistent with the view that ascites recirculation induces disseminated intravascular coagulation although this would appear to be only mild and of no clinical significance in the majority of patients. Although increased levels of activated factor VII were observed in ascitic fluid indicating activation of the extrinsic pathway of coagulation, a significant increase in plasma activated factor VII during the procedure was not demonstrated. Increased fibrinolytic activity was observed in ascitic fluid due to the presence of tissue plasminogen activator. Increased X oligomer levels were observed in ascitic fluid indicating that lysis of cross linked fibrin is also an active process within ascites. PMID- 2332594 TI - Prevention of impaired liver metabolism due to ischemia in rats. Efficacy of defibrotide administration. AB - The effect of defibrotide treatment in protecting liver metabolism from ischemic damage was studied. The drug was administered to male Wistar rats as a bolus (30 mg/kg body weight) at the beginning of 60 min ischemia and then continuously during 60 min of postischemic reperfusion at a dose of 30 mg/kg body weight. This dose was previously identified as useful to protect against myocardial ischemia induced in the cat. ATP and ADP intrahepatic levels were significantly higher in drug-treated rats than in untreated animals. The liver cytoplasmic NAD+/NADH ratio in defibrotide-treated rats was no different from that observed in sham operated rats. The mitochondrial NAD+/NADH ratio in the liver was also improved by defibrotide treatment. Our data suggest that defibrotide may exert protective activity on hepatocytes useful for inducing a rapid restoration of their metabolism. Such a restoration is possibly related to improvement of microcirculation through an increase in prostaglandin I2 production or oxygen delivery due to drug administration. PMID- 2332595 TI - Physico-chemical factors predisposing to pigment gallstone formation in liver cirrhosis. AB - Liver cirrhosis is associated with a high prevalence of pigmentary cholelithiasis. The major compound of pigment gallstones is unconjugated bilirubin (UCB) in the form of calcium bilirubinate salts or a black pigment polymer. Most of UCB in bile derives from enzymic or non-enzymic hydrolysis of mono- or diconjugated bilirubin. Changes in the relative ratios between these two bilirubin species have been associated with pigment gallstones. It has also been shown that UCB solubilization in bile depends on its interaction with bile salts. In order to clarify the factors predisposing cirrhotic patients to pigment stone formation, we measured UCB, monoconjugated bilirubin (MCB) and diconjugated bilirubin (DCB) in duodenal bile of 15 patients with cirrhosis, ten patients with chronic active hepatitis (CAH) and ten normal subjects, we also analyzed their relationships with lipids. In cirrhotic patients, the MCB concentration in bile was significantly (p less than 0.05) higher than in normal subjects and was correlated with the severity of the disease. Bile salts and lecithin concentrations were significantly lower in cirrhosis (p less than 0.005 vs. CAH or normals). Cirrhotic patients have a bile salts/UCB molar ratio which is one third that of CAH patients or normal subjects (p less than 0.01). No differences were found between CAH patients and controls in each of the parameters tested. In conclusion, we propose that the very low BS/UCB molar ratio and the very high biliary content in MCB represent two independent physico-chemical factors predisposing cirrhotic patients to pigmentary cholelithiasis. PMID- 2332596 TI - Phenobarbital hepatotoxicity in an 8-month-old infant. AB - Severe hepatotoxicity from phenobarbital occurred in an infant boy who had a complicated illness with chronic bilateral subdural hematomas and sepsis. Skin rash began after 2 weeks of treatment, and signs of hepatocellular failure developed 3 weeks after phenobarbital had been started. Signs of severe liver disease included elevated aminotransferases, conjugated hyperbilirubinemia, significant coagulopathy, hepatosplenomegaly and ascites. Other features of this adverse drug reaction were unremitting fever, leukocytosis with eosinophilia and atypical lymphocytosis, and proteinuria. Sepsis, viral hepatitis, and metabolic liver disease were excluded. The child was on no other medication and had been previously well. In-vitro rechallenge of the patient's lymphocytes with cytochrome P-450 generated metabolites of phenobarbital showed extensive cytotoxicity compared to control. These data support the hypothesis that a defect in drug detoxification was responsible for the child's susceptibility to this drug hepatotoxicity. PMID- 2332597 TI - Polymerase chain reaction for detection of the alpha-1-antitrypsin Z allele in chronic liver disease. AB - The genetic locus for alpha-1-antitrypsin (alpha-AT) is highly polymorphic, but all protein variants are encoded by a single locus on chromosome 14. Periportal hepatocyte granules are described in association with chronic liver disease and the Z variant. A Z-specific point mutation in exon V of the alpha-AT gene, converting amino acid 342 from Glu to Lys, is thought to be responsible for the hepatocyte accumulation. We describe the use of the polymerase chain reaction (PCR) to amplify exon V of the alpha-AT gene and subsequent detection of the wild type M- and Z-specific sequences by hybridisation to 32P-labelled-allele-specific oligonucleotides. We applied this technique to leucocyte DNA from 37 patients with suspected chronic liver disease, 25 of whom had hepatocyte alpha-AT inclusion granules on liver biopsy. All 25 were homozygous or heterozygous for the Z allele. One patient, phenotyped as PiS, was found to be PiSZ and another phenotyped as PiZ (presumed homozygous), was found to be a Z heterozygote. No Z allele was detected in any of the twelve patients without alpha-AT inclusion granules. This sensitive PCR technique could be used to assess the relative risk of chronic liver disease in PiZ heterozygotes and to determine whether individuals without the Z amino acid 342 substitution can developed periportal alpha-AT granules. PMID- 2332598 TI - A new hepatitis B virus strain in patients with severe anti-HBe positive chronic hepatitis B. AB - In hepatitis B virus carriers who are anti-HBe positive despite ongoing viral replication (HBcAg in liver and HBV-DNA in serum) the natural course of hepatitis is severe and the response to interferon is low. We investigated whether a new hepatitis B virus (HBV) strain could be involved. A translational termination codon at the carboxyterminal end of the pre-C region responsible for the lack of HBeAg secretion was found in 18 of 19 HBV clones isolated from seven pedigreed patients with this clinical syndrome. The same findings were confirmed by direct sequencing. One of these patients underwent a liver transplant and HBV infection of the new liver resulted in high titered viremia and intrahepatic expression of HBcAg, without detectable HBeAg in serum. Another patient was superinfected by hepatitis delta virus (HDV) and developed high titres of total and IgM anti-HD. In spite of this, chronic hepatitis remained unchanged during 7 years of follow up. These data strongly suggest that a viable precore minus mutant of hepatitis B virus is responsible for the lack of HBeAg in the serum of these patients. The HBV variant may explain the peculiar geographic distribution of anti-HBe positive hepatitis. The variations in the virus genome sequence may cause the more severe form of liver disease and modify the pathogenicity in the case of HDV superinfection. PMID- 2332599 TI - Zeroing in on the appropriate management of occupational exposures to HIV-1. PMID- 2332600 TI - The choice of microcomputer software for infection control. PMID- 2332601 TI - A comparison of infection control software for use by hospital epidemiologists in meeting the new JCAHO standards. AB - To choose a microcomputer software package for our hospital epidemiology division, the two leading commercial software packages for infection control, AICE (ICPA, Inc., Austin, Texas) and NOS0-3 (Epi Systematics, Inc., Ft. Meyers, Florida), were compared for the types of epidemiologic analysis likely to be required to satisfy new Joint Commission on Accreditation of Healthcare Organizations (JCAHO) 1990 Infection Control Standards. The test dataset was a surgical database of 3,235 operations with 292 (9%) wound infections. Though NOSO 3 was more flexible in terms of the amount of data items one could record, it required seven times longer to learn, nine times more disk space to store and two times as long to enter cases than AICE. Six simple infection control reports (i.e., line listings, crosstabulations, stratified rates and graphs) required only seven computing steps and approximately 11 minutes to process with AICE, but 22 steps and over two hours with NOSO-3. All analytic results from AICE agreed with the results obtained with the Statistical Analysis System (SAS, SAS Institute, Inc., Cary, North Carolina), but analyses such as service-specific rates performed with NOSO-3 differed because of a design flaw in the NOSO-3 data structure. PMID- 2332602 TI - Increasing ICU staff handwashing: effects of education and group feedback. AB - This study provides an evaluation of the effectiveness of methods to increase handwashing (HW) by nurses working in an intensive care unit. After baseline observations, two interventions were implemented in sequence: three series of classes conducted by the infection control nurse (ICN); and feedback to staff about handwashing errors on the previous day. Staff were aware that handwashing was being observed throughout the study. The educational intervention produced an immediate increase in HW that was followed by a decline to baseline rates over four weeks. Feedback produced an improvement to 97% compliance that was sustained until completion of the study. Improvement in HW compliance following specified critical procedures was also observed following interventions. PMID- 2332603 TI - Brief report: reduction in the frequency of needle recapping by effective education: a need for conceptual alteration. PMID- 2332604 TI - AIDS and long-term care facilities. PMID- 2332605 TI - Toxoplasma gondii. AB - Toxoplasmosis encompasses a variety of clinical conditions. Serious sequelae are seen in congenital toxoplasmosis and in infections of the immunocompromised host. In the former, prevention of maternal acquisition of toxoplasmosis during pregnancy is paramount. Infection in the compromised host often presents with neurologic abnormalities. Unfortunately, the HIV syndrome itself or other opportunistic infections can present in a similar manner. Often, empiric treatment for toxoplasmosis is begun based on clinical findings and an enhancing lesion noted on the head CT. Pyrimethamine and sulfadiazine remain the drugs of choice for toxoplasmosis and are able to penetrate blood-brain barriers. Currently, trials using other agents are in progress. PMID- 2332606 TI - The chronic efficacy of midazolam. AB - The chronic efficacy of midazolam 15.0 mg was studied in 2 male and 10 female subjects. Only subjects with a complaint of sleep latency insomnia which was verified by polysomnography were included in the study. Following a screening and adaptation period, subjects spent 3 consecutive nights in the laboratory during the weeks of the study. Placebo was administered 15 min before lights out on the initial 8 and final 2 nights, and midazolam for the intervening 35 nights. Midazolam significantly reduced sleep latency parameters and significantly increased total sleep time the entire 5 weeks of nightly administration. No within-night rebound insomnia, residual daytime effects, or rebound effects upon discontinuation appeared. PMID- 2332607 TI - Clinical and experimental studies on fluoxetine: effects on serotonin uptake. AB - A decreased rate of uptake of serotonin (5HT) into platelets is recognized as a possible marker of the depressed state, being normalized only by effective antidepressant treatment. Fluoxetine is a novel antidepressant, with 5HT uptake inhibitory properties. In this study, treatment of depressed patients with fluoxetine for up to 6 months did not normalize the decreased platelet 5HT uptake rates associated with depression, although the patients showed a clinical recovery. The olfactory bulbectomized (OB) rat shows a characteristic hyperactivity in a stressful environment, which can be reversed only by chronic treatment with most antidepressants. OB rats have been found to exhibit a decreased rate of platelet 5HT uptake, similar to depressed patients, which is normalized by chronic antidepressant treatment. However, 3 weeks treatment with fluoxetine failed to reverse the hyperactivity of the OB rat and the decreased rates of uptake of 5HT. We also examined the rate of uptake of serotonin into the synaptosomes of the OB rats, in order to elucidate whether platelet 5HT uptake reflected central activity. Chronic fluoxetine treatment failed to normalize high affinity synaptosomal 5HT uptake in the OB rat. Fluoxetine, therefore, unlike most other antidepressants, does not normalize the decreased rates of platelet 5HT uptake in depressed patients on clinical recovery. OB rats also showed a deficit in their platelet and synaptosomal 5HT uptake rates, following 3 weeks treatment with fluoxetine. PMID- 2332608 TI - Comparison of the effect of two prazepam formulations on psychomotor and cognitive function in healthy volunteers. AB - A double-blind crossover design was used to evaluate the effect of two different formulations of prazepam, on motor and cognitive functions and subjective symptoms. Ten healthy male volunteers received 20 mg of prazepam both in tablet and liquid (as drops) formulation, separated by a 1 week interval. All subjects completed a battery of 9 performance tests 2.25 h and 4.75 h after drug intake (corresponding to the times of peak plasma concentration). They also rated themselves on eight visual analogue scales before, 2 h, 4.5 h and 8 h following drug intake. A significant difference between liquid drops and tablets was demonstrated in 4 of the 9 performance tests and 2 of the 8 items of the self rating scales. These results suggest that a single dose of prazepam administered in liquid drop form exhibits greater sedative properties than the same dose administered as tablets in healthy volunteers, probably as a result of more rapid absorption. PMID- 2332609 TI - Pharmacokinetics of lithium in patients treated with controlled release lithium formulations. AB - There has long been discussion as to the relative merits of the lithium formulations available in the UK. Two of these have been shown to exhibit similar pharmacokinetics in normal volunteers and both are now marketed as controlled release formulations. In this study the serum lithium profiles of these formulations were compared in patients at two centres during the first 4 h after the dose, and at 24 h. We were unable to show any significant difference between the formulations in respect of maximum serum lithium concentrations or the concentration at each time point. PMID- 2332610 TI - The genetics of host-pathogen coevolution: implications for genetic resource conservation. AB - The results of long-term studies of coevolution in the Hordeum vulgare Rhynchosporium secalis pathosystem are summarized. The genetic systems of barley (host) and R. secalis (pathogen) are complementary: Gene-for-gene interactions among loci affect many traits, leading to self-regulating adjustments over generations between host and pathogen populations. Different pathotypes differ widely in their ability to damage the host, and different host-resistance alleles differ widely in their ability to protect the host from the pathogen. Among 29 resistance loci in the specific host population studied, several played major roles in providing stable resistance, but many had net detrimental effects on the yield and reproductive ability of the host. Resistance alleles that protected against the most damaging pathotypes increased sharply in frequency in the host populations. It is concluded that the evolutionary processes that take place in genetically variable populations propagated under conditions of cultivation can be highly effective in increasing the frequency of desirable alleles and useful multilocus genotypes. This enhances the value of the evolving populations as sources of genetic variability in breeding for disease resistance and other characters that affect adaptedness. PMID- 2332611 TI - Genetic and germ plasm stocks worth conserving. AB - The relative costs and benefits of genetic stock collections and germ plasm collections are discussed. The status of national and international collections is compared with the needs of plant breeders and geneticists. There is an international need for germ plasm systems that emphasize the use and employment of materials rather than acquisition and storage. For base collections to function, they must provide for regeneration, characterization, documentation, and evaluation of their materials. The quality of a germ plasm system should be judged on the basis of the quality of the materials available to scientists. Adequate quantities of high-quality seed that are of known provenience, spanning the range of known genetic diversity, promptly delivered, and well described constitute the minimum that should be expected. All too often such minimal requirements are not met. PMID- 2332612 TI - Evolution of the mojavensis cluster of cactophilic Drosophila with descriptions of two new species. AB - The mojavensis cluster of the repleta species group of Drosophila (Drosophilidae: Diptera) consists of three species. One is newly described as D. navojoa. A second species, described here as D. arizonae, replaces D. arizonensis, which has become a junior subjective synonym for D. mojavensis, the third species in the cluster. A phylogeny of the three species is presented, based on chromosomal inversions, morphology, and the ability to produce hybrids. Breakage points are assigned for all inversions, and male genitalia are figured; 186 crosses were made from 225 possible combinations among 15 geographic strains from the southwestern United States, Mexico, and Guatemala. It is confirmed that D. mojavensis and D. arizonae are very closely related and shown that D. navojoa is more distantly related in regard to all criteria. This relationship is supported by the geographical positions of the ancestral gene sequences in each species, which show a sequential northwest movement (D. navojoa----D. arizonae----D. mojavensis) from southern Mexico to southern California and northern Arizona. The relationship is also supported by the fact that D. navojoa breeds in Opuntia cactus, an ancestral behavior, whereas the other two species breed chiefly in Stenocereus cacti, a derived behavior. The possible role of this host plant shift in speciation is discussed. PMID- 2332613 TI - Patchy fur (Paf), a semidominant X-linked gene associated with a high level of X Y nondisjunction in male mice. AB - Several X-linked mutations that have associated sex chromosomal nondisjunction have been identified in the mouse. We describe a new semidominant X-linked mutation called patchy fur (Paf) that produces an abnormal coat. It maps to the distal end of the murine X chromosome very near the XY pseudoautosomal region. The degree of severity in affected mice is hemizygous males greater than homozygous females greater than heterozygous females. An unusual feature of Paf is that either the mutation itself or an inseparable chromosomal abnormality causes delayed disjunction of the X and Y chromosomes at meiotic metaphase I, which in turn results in approximately 19% XO progeny and slightly less than 1% XXY progeny from Paf/Y males. The effect occurs only in male carriers and thus must extend into the proximal end of the XY pairing region. PMID- 2332614 TI - Heritability of brain size and surface features in rhesus macaques (Macaca mulatta). AB - The extent of heritability for overall brain size and regional cortical surface features such as sulcus lengths is important for demonstrating a genetic component to the observed phenotypic differences among individuals and for evaluating the potential for evolutionary change in response to selection. Although the genetics of brain size has been extensively considered, the detailed morphology of the cortical surface has not previously been subjected to genetic analysis. We estimated the heritability of brain size and cortical sulcus lengths using 438 endocranial casts taken from skeletons of rhesus macaques (Macaca mulatta) from the Cayo Santiago population. Estimates were obtained both by mother-offspring regression and symmetric-differences-squared (SDS) methods. Brain size, measured as cranial capacity, was highly and significantly heritable in this population, confirming results of previous studies with laboratory mice. Overall, cortical sulcus lengths were also heritable, with 35% of the sulci significantly heritable at the 5% level in the mother-offspring analysis. The average mother-offspring heritability estimate, 0.31, was the same as the average heritability obtained previously from a series of 56 cranial metric characters. The SDS analyses generally corresponded to the findings based on mother-offspring regressions, although the significance test appeared more conservative. Both gross and detailed morphology of the brain are heritable. PMID- 2332616 TI - An improved characterization of cattle chromosomes by means of high-resolution G- and R-band comparison. AB - An improved characterization of cattle chromosomes was obtained by means of high resolution G- and R-band comparison. Models of G- and R-banded karyotypes that were arranged according to the Reading system and the previous RBA-banded karyotype were obtained at the 475 band level by using early- and late-BrdU incorporation in synchronized cell cultures. As in human chromosomes, only one common G- and R-banding nomenclature is proposed. PMID- 2332615 TI - Chromosomal and protein evolution in morphologically similar species of Praomys sensu lato (Rodentia, Muridae). AB - Evidence of extensive chromosomal evolution in a biologically and economically important group of African murids of the Praomys/Mastomys complex was provided by examination of G- and C-band chromosomal data on P. coucha (2n = 32), P. fumatus (2n = 38), P. hildebrandti (2n = 32), P. jacksoni (2n = 28), P. misonnei (2n = 36), and P. cf. tullbergi (2n = 35). A coding system was developed for the chromosomal characters, and analyses were performed by a computer program to find the shortest tree with a minimum of 35 autosomal rearrangements (pericentric inversions, complex translocations, centric fusions, centric fissions, tandem fusions, euchromatic additions, and heterochromatic additions). The resulting phylogenetic hypothesis differs from traditionally accepted hypotheses regarding this complex group of rodents. The cytogenetic data show that 1) there is no support for the dichotomy of Mastomys/Praomys previously based on morphology, 2) the 2n = 32 species from eastern Africa (P. hildebrandti) is distinct from the 2n = 32 species from southern Africa (P. natalensis), and 3) there is a close association between P. jacksoni and P. cf. tullbergi. Polyacrylamide gel electrophoresis of liver membrane proteins demonstrated few differences in protein mobilities between species and even fewer between individuals of the same species taken from different habitats and localities in Kenya. Monoclonal antibodies produced against liver proteins of one species and tested for reactivity to other species confirmed the evolutionary similarity of species of this complex. This immunologic approach may provide a robust data set for future phylogenetic studies of muroid rodents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332617 TI - One-month-old infant with vomiting. PMID- 2332619 TI - Problem solving. AB - Students and physicians sometimes struggle with the bedside decision-making process. The following text details a problem-solving algorithm that has evolved and has been tailored to and by clinical practice. PMID- 2332618 TI - Trigger finger and thumb. PMID- 2332620 TI - Eosinophilia myalgia syndrome: case report. PMID- 2332621 TI - Improving communications can prevent malpractice. PMID- 2332622 TI - The economics of medical care, 1940 to 1991. PMID- 2332623 TI - High-resolution immunogold localization of Giardia cyst wall antigens using field emission SEM with secondary and backscatter electron imaging. AB - We describe here the ultrastructural localization of Giardia cyst antigens in the filaments associated with the outer portion of intact cysts and on developing cyst wall filaments in encysting trophozoites. Post-embedding immunogold labeling of thin sections of intact Giardia cysts with polyclonal and monoclonal antibodies specific for cyst wall antigens (major protein bands of approximately 29, 75, 88, and 102 KD on Western blots) showed strong labeling of the filamentous cyst wall, whereas no labeling was seen on the membranous portion. High-resolution field emission scanning electron microscopy (FESEM) of Giardia cysts revealed that the cyst wall-specific polyclonal rabbit antisera and monoclonal mouse antibody produced gold labeling of 20-nm filaments in the cyst wall as detected with secondary electron imaging (SEI) and backscatter electron imaging (BEI) at 10 kV, despite coating of the cells with platinum by ion sputtering. FESEM studies of encysting Giardia trophozoites demonstrated that immunostaining with antibodies to cyst wall antigens produced colloidal gold labeling of developing cyst wall filaments on the cell surface; however, the intervening membrane domains were unlabeled. Substitution of normal serum for cyst wall-specific antibodies, or preabsorption of specific antibodies with Giardia cysts, eliminated immunolabeling of the filaments. PMID- 2332624 TI - Association of adenosine deaminase with erythrocyte and platelet plasma membrane: an immunological study using light and electron microscopy. AB - Adenosine deaminase has been localized in the plasma membrane of erythrocytes and platelets by means of immunological techniques using light and electron microscopy with cells in suspension. In erythrocytes, adenosine deaminase is associated with the external side of the plasma membrane. In platelets, the enzyme is associated with the external side of the plasma membrane, which is known to extend through the canalicular system of these cells. These results confirm our previous findings, based on biochemical studies, concerning the attachment of the enzyme to cell membranes. PMID- 2332625 TI - Proteoglycan distribution in developing rabbit cornea. AB - We used a staining procedure specific for sulfated glycosaminoglycans, cuprolinic blue dye (CBD), and immunohistochemical techniques to determine the histological distribution and ultrastructural organization of proteoglycans in developing rabbit cornea. We found several types of CBD-stained structures located throughout the corneal stroma, indicative of the distribution and perhaps the chemical heterogeneity of proteoglycans in this tissue. Keratan sulfate-specific immunohistochemical evidence supports our cytochemical findings. Our results suggest that low-sulfated keratan sulfate proteoglycans are found throughout most of the developing stroma, with the exception of the posterior margin of this tissue. Highly sulfated keratan sulfate proteoglycans in young fetal corneas, initially restricted to the subepithelial stroma, progressively extend to deeper portions of the stroma with development. Dermatan sulfate proteoglycans are located throughout the stroma, including the posterior margin. Invoking a recently published "oxygen-lack hypothesis" and correlating the tissue location of proteoglycans with the source of oxygen, we hypothesize that the distribution of proteoglycans in the developing rabbit cornea is related to the selective synthesis of keratan sulfate glycosaminoglycans under hypoxic conditions. PMID- 2332626 TI - Modulation of glycogen stores in epithelial cells during airway development in Syrian golden hamsters: a histochemical study comparing concanavalin A binding with the periodic acid-Schiff reaction. AB - We studied glycogen storage in the developing airway epithelium of Syrian golden hamsters from gestational Day 11 to neonatal Day 2 using concanavalin A (ConA) staining as an adjunct approach to the periodic acid-Schiff (PAS) reaction. One hundred and fourteen fetuses and neonates were fixed in 4% formaldehyde-1% glutaraldehyde, 6% mercuric chloride-1% sodium acetate-0.1% glutaraldehyde, and 95% ethanol, embedded in paraffin, and stained with ConA-horseradish peroxidase conjugate as well as with PAS. ConA staining was abolished by alpha-glucosidase digestion or by pre-treatment with periodic acid, demonstrating that ConA bound to glycogen. In tissues fixed with mercury and/or aldehydes, ConA staining was greatly enhanced by pepsin digestion. Airway glycogen stores, revealed by ConA and PAS, fluctuated during development. At first all the undifferentiated epithelial cells contained abundant glycogen. Then, coincident with the appearance of the first endocrine cells, the glycogen stores were depleted. Thereafter, glycogen accumulated in pre-secretory and basal cells until birth, but by 2 days after birth the glycogen stores were again depleted. The initial depletion of glycogen followed by repletion was observed at all levels of the conducting airways; changes in the trachea preceded those in the bronchi and bronchioles by 1 and 2 days, respectively. PMID- 2332627 TI - Iontophoretic injection of fluoro-gold and other fluorescent tracers. AB - Fluoro-gold, a retrograde axonally transported fluorescent tracer, has been successfully iontophoresed into brain regions to yield small injection sites with no detectable dye along the track. Previous difficulties involving iontophoretic application of fluoro-gold were overcome through the use of a cacodylate vehicle. This vehicle was also found to be suitable for iontophoresing other fluorescent tracers, such as propidium iodide or Fast Blue. PMID- 2332628 TI - Adoptively transferred antigen-specific T cells can be grown and maintained in large numbers in vivo for extended periods of time by intermittent restimulation with specific antigen plus IL-2. AB - The aim of the current study was to determine whether cultured tumor Ag-specific T cells could be induced to grow and maintained functional in large numbers in vivo by intermittent restimulation in vivo with specific Ag plus IL-2. T cells derived from spleens of B6 mice (Thy-1.2) immune to FBL-3, a Friend virus-induced leukemia, were activated by in vitro stimulation with irradiated FBL-3 and expanded by culture for 14 days with low concentrations of IL-2. The resultant FBL-3-specific T cell lines were adoptively transferred into cyclophosphamide pretreated congenic hosts (B6/Thy-1.1), and restimulated every 14 days by an injection of irradiated FBL-3 plus a 7-day course of IL-2. Donor T cells residing in the host were identified and quantified by use of antibody to the Thy-1.2 allele. The results confirmed that stimulation with FBL-3 on the day of transfer (day 0) plus IL-2 on days 0 to 6 induced rapid growth of donor T cells to approximately an 11-fold increase in total donor T cell number recoverable from host ascites and spleen by day 7. However, prolonging the course of IL-2 administration to 35 days did not maintain the number or the specific cytolytic function of donor T cells. By contrast, intermittent restimulation with specific Ag plus IL-2 induced intermittent regrowth of donor T cells in vivo, maintained the number of donor T cells in vivo at greater than the number input for longer than 1 mo, and allowed detection of substantially augmented donor T cell-mediated specific antitumor function over that period of time. PMID- 2332629 TI - Human alveolar macrophage FcR-mediated cytotoxicity. Heteroantibody- versus conventional antibody-mediated target cell lysis. AB - Human alveolar macrophage have three distinct receptors for IgG: FcRI, FcRII, and FcRIII. In order to compare the ability of these receptors to mediate target cell lysis, three different assay systems were examined. First, we studied lysis of chicken E (CE) opsonized with heteroantibodies, which are synthetic antibodies composed of Fab fragments with anti-FcR activity covalently linked to Fab fragments with anti-CE activity. We found alveolar macrophage readily lysed heteroantibody-opsonized CE via each of the three FcR classes (FcRI, 20 +/- 5%; FcRII, 27 +/- 7%; and FcRIII, 13 +/- 13%, p less than 0.05). Non-FcR-dependent lysis of anti-beta 2-microglobulin x anti-CE heteroantibody-opsonized CE was not detected. Second, lysis of hybridoma cell lines bearing anti-FcR antibodies on their cell surface was examined to assess killing of "tumor-like" target cells. Whereas peripheral blood monocytes and lymphocytes were able to lyse hybridoma cell lines bearing surface anti-FcR mAb, alveolar macrophages were not. Third, activity of alveolar macrophage FcR was examined in a conventional antibody dependent cellular cytotoxicity assay by using O+ (R1,R2) human RBC opsonized with human anti-D and anti-CD serum as target cells. We found lysis of anti-D and anti-CD opsonized human RBC was mediated exclusively via FcRI. No activity of FcRII or FcRIII was detected in these latter assays even if performed under conditions that impair FcRI activity. Thus, all three FcR present on alveolar macrophage mediate lysis of heteroantibody-opsonized CE; in contrast, with the use of a conventional antibody-dependent cellular cytotoxicity assay, only FcRI activity was detected. We were unable to demonstrate lysis of anti-FcR-bearing hybridoma cell lines by alveolar macrophages. PMID- 2332630 TI - Persistence of donor-specific IL-2-secreting cells and cytotoxic T lymphocyte precursors in human kidney transplant recipients evidenced by limiting dilution analysis. AB - The low reactivity to donor alloantigens reported in PBL from kidney transplant recipients might be related to clonal deletion and/or suppression of donor specific alloreactive cells. To discriminate between these two hypotheses, we quantified the number of IL-2 secreting cells (IL-2-SC) and of cytotoxic precursors (CTLp) in the T cells from tolerant recipients when stimulated with either donor specific or nonrelated third-party LCL. To eliminate the irrelevant reactivity, we used as responding cells high-density T cells that had been depleted of such reactivity by 4 days preculture with autologous lymphoblastoid cell line in the presence of bromodeoxyuridine. Thus, frequencies of IL-2-SC and CTLp specifically directed at alloantigens could be measured. In 11 recipients, there was no strong decrease in the frequency of donor-reactive T cells when compared to the frequency of those directed at a third-party lymphoblastoid cell line, either for IL-2-SC (tested in 11 patients) or for CTLp (tested in 6 patients). In three cases of seven, a suppression was observed only when T cells were stimulated by donor cells. These data suggest that donor-reactive cells are still present in PBL of kidney-transplant recipients tested from 6 mo to 4 y posttransplantation. Moreover, suppression of donor-specific cells can be demonstrated in peripheral T cells of some recipients, which may account in part for the absence of rejection. PMID- 2332631 TI - IL-1 beta modulation of spontaneous autoimmune diabetes and thyroiditis in the BB rat. AB - Long term effects of in vivo treatment with human rIL-1 beta on diabetogenesis and thyroid disease were determined in the Biobreeding rat. Administration of high dose (10 micrograms/kg) IL-1 beta accelerated the onset of insulin-dependent diabetes mellitus compared to saline-injected controls. High dose treatment resulted in goiter development, pronounced LT, reduced serum T4 levels, and overall growth reduction. In contrast, low dose IL-1 beta (0.5 microgram/kg) administration significantly reduced the frequency of insulin-dependent diabetes mellitus (48%) compared to placebo (86%) and high dose IL-1 beta (93%) treatment groups. Rats protected by low dose IL-1 beta had unaffected growth rates and minimal to no pancreatic and thyroid pathology. Our results demonstrate that exogenous administration of IL-1 beta modulates Biobreeding rat idiopathic autoimmune diabetes and thyroid disease in a dose-dependent manner. PMID- 2332632 TI - Expression of murine IL-2 receptor beta-chain on thymic and splenic lymphocyte subpopulations as revealed by the IL-2-induced proliferative response in human IL 2 receptor alpha-chain transgenic mice. AB - Lymphocytes from the human (h) IL-2R alpha chain transgenic mice (TGM) constitutively express high affinity binding sites for hIL-2, consisting of transgenic h-IL-2R alpha and endogenous murine IL-2R beta, and therefore easily proliferate in vitro in response to hIL-2. Our study was undertaken to clarify the hIL-2-responsive lymphocyte subsets in the TGM, which should most likely reflect the normal distribution of m IL-2R beta expression. In both thymus and spleen, the majority of expanded cells by hIL-2 was CD3+CD4-CD8+ TCR alpha beta+ cells. The proliferation of CD4+ cells was not observed at all from either organ despite the expression of transgenic hIL-2R alpha. Potent cellular proliferation was also observed from the thymocytes that had been depleted of CD8+ cells, the expanded cells consisting of CD3- (15-40%) and CD3+ populations (60-85%). Among CD3+ cells, approximately the half portion expressed TCR alpha beta, whereas the other half was suggested to express TCR gamma delta. A variable portion (5-20%) of the CD3+ cells expressed CD8 (Lyt-2) in the absence of Lyt-3, and the CD3+CD8+ cells were confined preferentially to the TCR alpha beta- (TCR gamma delta+) population. In the culture of splenocytes depleted of CD8+ cells, however, the proliferated cells were mostly CD3-CD4-CD8-TCR-Mac1-, whereas a minor portion (10 30%) was CD3+CD4-CD8-TCR alpha beta- (TCR gamma delta+. Analysis of TCR genes at both DNA and mRNA levels confirmed the phenotypical observations. These results strongly suggested that IL-2R beta was constitutively and selectively expressed on the primary murine thymocytes and splenic T and NK cells, except for CD4+ cells in both organs. PMID- 2332633 TI - Evaluation of antisperm complement-dependent immune mediators in human ovarian follicular fluid. AB - A "sandwich"-type radiolabeled antiglobulin assay using monoclonal anti-C5b-9 neoantigen and polyclonal anti-C5b-9 was used to evaluate the presence of terminal C complexes (SC5b-9 or MC5b-9) in the sera and ovarian follicular fluid (FF) from 45 infertile women. FF SC5b-9 was detectable in all clinical diagnostic categories. The mean SC5b-9 levels in FF and sera were 399 ng/ml (range 75 to 1350 ng/ml) and 798 ng/ml (range 0 to 2700 ng/ml), respectively. Twelve (26.6%) of the 45 FF samples had normal hemolytic C activity, and all FF (n = 44) samples initiated C8/C9-dependent lysis of sensitized sheep E coated with human C1-7. Human plasma IgG antisperm antibodies (ASA) were capable of activating C in 31 (72%) of 43 FF samples as detected by their ability to deposit MC5b-9 on human sperm. Sera from infertile women with ASA in their sera and FF impaired human sperm binding to human zona pellucida and binding and penetration of zona-free hamster oocytes in vitro. The discovery of SC5b-9 and MC5b-9 in ovarian FF implies that the interaction of ASA and C could have a deleterious effect on sperm during in vivo and in vitro sperm-egg interactions in women with antisperm antibodies. PMID- 2332634 TI - Clonotypes of anti-DNA antibodies expressing specific idiotypes in immune complexes of patients with active lupus nephritis. AB - IEF, using 6 M urea, provides a unique opportunity to analyze the spectrotypes of antibodies in immune complexes (IC) in vivo. Using this technique, we have analyzed the clonotypes of anti-DNA antibodies expressing specific Id in the circulating IC of patients with active lupus nephritis. Serum anti-ssDNA and anti dsDNA antibodies showed heterogeneous spectrotypes. The antibodies isolated from circulating IC had a restricted clonotype and a neutral charge and were directed mainly to ssDNA and, to a lesser extent, to dsDNA. These samples failed to form complexes with DNA when they were subjected to absorption to a DNA-coupled Sepharose column. Anti-DNA antibodies expressed specific Id, termed O-81 or NE-1, which were detected only in the IC of patients with active lupus nephritis. Anti DNA clonotypes, including O-81 and NE-1 idiotypes, were also found in the eluates of renal glomeruli of lupus patients. These results indicate that subpopulations of anti-DNA antibodies in circulating IC are limited, and may play an important role in the pathogenesis of lupus nephritis. PMID- 2332635 TI - Temporal expression of different pathways of 1-arginine metabolism in healing wounds. AB - Arginine can be metabolized by inflammatory cells through at least two pathways. One is an oxidative l-arginine deiminase (OAD) that results in the formation of citrulline and reactive nitrogen intermediates. The other is arginase, which determines the production of ornithine and urea. The temporal expression of these pathways in an experimental wound model (s.c. implanted polyvinyl alcohol sponges in the rat) was investigated by examining the concentrations of amino acids and of nitrite in fluids obtained from the sponges 6 h to 15 day after implantation. These analyses revealed two distinct periods during which the arginine concentration in the fluids was markedly below plasma levels. During the early period (less than 3 days after sponge implantation) wound fluid contained more citrulline and nitrite than at any other time, suggesting OAD activity. In contrast, ornithine accumulated in the fluids during the late decrease in arginine concentration that extended beyond day 3, during which time the wound fluid also contained a high arginase activity. This time-dependent expression of different pathways of arginine metabolism in wounds was confirmed in sponge cultures containing [guanido-14C]-l-arginine. Cells contained in sponges harvested less than 48 h after implantation metabolized labeled arginine mainly to labeled citrulline, whereas labeled urea was produced during culture of sponges harvested after this time. The low arginine content of wound fluid did not appear to be rate limiting for the expression of OAD in late sponges because no OAD activity was evidenced when 4 mM arginine was added to the cultures. These results indicate that the OAD pathway is expressed in this model predominantly during the early, polymorphonuclear leukocyte-predominant, phase of repair. At this time, the reactive nitrogen intermediates resulting from the metabolism of arginine may mediate some of the events characteristic of early inflammation, including microbiostasis, vasodilation, and inhibition/reversal of platelet aggregation. In turn, the late suppression of this pathway and the catabolism of arginine through arginase may promote macrophage function within wounds. PMID- 2332636 TI - Inhibition of antigen-induced airway hyperresponsiveness, but not acute hypoxia nor airway eosinophilia, by an antagonist of platelet-activating factor. AB - The role of platelet-activating factor (PAF) in Ag-induced airway hyperresponsiveness was evaluated in a guinea pig model using the PAF antagonist SDZ 64-412. Repeated OVA challenge by aerosol (twice weekly x 4 wk) of previously sensitized guinea pigs produced striking airway hyperresponsiveness as determined by pulmonary resistance changes to increasing doses of inhaled acetylcholine given 3 days after the last OVA challenge. Each OVA challenge produced significant hypoxia that was unaffected by oral pretreatment with 20 mg/kg SDZ 64 412, 2 h before each challenge (pO2 = 35 +/- 2 mm Hg for OVA alone vs 40 +/- 6 mm Hg for SDZ and OVA groups, respectively). SDZ 64-412 pretreatment abolished the airway hyperresponsiveness resulting from repeated Ag challenge. Morphometric analysis revealed that SDZ 64-412 treatment had no effect on the increased numbers of eosinophils that infiltrated the airways of OVA-challenged guinea pigs. These results suggest that PAF may be a primary mediator of airway hyperresponsiveness, but not acute bronchoconstriction, induced by repeated Ag challenge. This activity of PAF appears independent of eosinophil recruitment to airways. PMID- 2332637 TI - Eosinophil degranulation. An immunologic determinant in the pathogenesis of the Mazzotti reaction in human onchocerciasis. AB - Onchocerciasis patients treated with diethylcarbamazine often undergo a severe inflammatory response, the Mazzotti reaction. To assess the eosinophil's role in the pathogenesis of the Mazzotti reaction, we obtained serial blood, plasma, and skin biopsy specimens from 21 heavily infected patients and 3 endemic controls, both before and during therapy with diethylcarbamazine. Samples were analyzed for blood eosinophils, plasma levels of eosinophil granule major basic protein (MBP) and eosinophil-derived neurotoxin, eosinophil infiltration and eosinophil and mast cell degranulation in the skin. After the first dose of diethylcarbamazine, blood eosinophils fell from a pre-treatment level of 888 +/- 111 to 203 +/- 42 cells/mm3 at 8 h. This decrease was followed by a marked eosinophilia developing over the remaining 7 days of treatment and 14 days of follow-up. Plasma eosinophil-derived neurotoxin levels increased from 56 +/- 4 ng/ml pretreatment to a peak of 82 +/- 9 ng/ml at 8 h and returned to pretreatment levels by 48 h. Beginning at 12 h, plasma MBP levels increased from 730 +/- 74 ng/ml pretreatment to a peak of 1140 +/- 74 ng/ml after 5 days. Pretreatment skin biopsies stained for MBP by immunofluorescence showed a bright fibrillar pattern in the dermis consistent with chronic eosinophil degranulation; the MBP was localized on elastic tissue fibers. After treatment, skin biopsy specimens showed both the pretreatment fibrillar MBP staining pattern as well as focal eosinophil degranulation. Deposition of MBP around microfilariae in the papillary dermis was visible as early as 1.5 h. The lowest blood eosinophil levels and peak plasma eosinophil-derived neurotoxin levels coincided with the infiltration and degranulation of eosinophils in the skin. Mast cell degranulation in the skin was maximal by the first posttreatment biopsy (1.5 h) coincident with the beginning of eosinophil degranulation. Although the pathogenesis of the Mazzotti reaction is clearly complex, our results indicate that eosinophil degranulation is characteristic of the response and that it occurs with a time course suggestive of a role for the eosinophil in determining the clinical and pathologic manifestations of the reaction. PMID- 2332638 TI - The gene sequence and some properties of protein H. A novel IgG-binding protein. AB - The gene for protein H, a novel bacterial cell wall protein with specific affinity for human IgG Fc, was cloned from a group A Streptococcus and expressed in Escherichia coli. Recombinant E. coli cells produced two forms of a human IgG Fc-binding protein, one with an apparent Mr of 42 kDa in a periplasmic fraction and the other with an apparent Mr of 45 kDa in a mixed fraction of cytoplasms and membranes. Both 42-kDa and 45-kDa protein preparations similarly bound to human IgG1 to IgG4, human IgG Fc, and rabbit IgG, but not to IgG of mouse, rat, bovine, sheep, goat, and human IgA, IgD, IgE, and IgM. The complete nucleotide sequence of the cloned 1.8-kb DNA fragment was determined. An open reading frame encoded a hypothetical protein of 376 amino acid residues (Mr = 42,498). The N-terminal amino acid sequence, consisting of 41 residues, which was removed post translationally had typical characteristics of Gram-positive bacterial signal peptides. Thus, the mature form of protein H was suggested to consist of 335 residues (Mr = 38,162). There were 3 repeated sequences consisting of 42 residues that were highly homologous to those of protein Arp, an IgA-binding streptococcal cell wall protein, and streptococcal M6 and M24 proteins. The C-terminal amino acid sequence consisting of 93 residues, directly following the repeated sequences, was also highly homologous to that of M6 and M24 proteins. No sequence homology was found between protein H and protein A or protein G, two other IgG binding bacterial cell wall proteins. PMID- 2332639 TI - Rejection of mouse sarcoma cells after transfection of MHC class II genes. AB - Th cells are stimulated by peptide Ag presented in the context of MHC class II molecules. We have reasoned that immune responses against tumors may be more efficient if tumor cells were class II Ag positive, and thereby able to directly function as APC to stimulate tumor-specific Th cell proliferation. We have tested this hypothesis by using DNA-mediated gene transfer to generate syngeneic MHC class II Ag-expressing mouse Sal sarcoma cells (Sal/Ak transfectants). Autologous A/J mice challenged i.p. or s.c. with Sal/Ak transfectants do not develop tumors, whereas A/J mice challenged with the class II negative parental Sal tumor have a high tumor incidence. Furthermore, immunization of the autologous host with Sal/Ak transfectants completely protects against subsequent challenge with wild type Sal cells. MHC class II-expressing tumor cells, therefore, stimulate an improved tumor-specific immune response, and the immunity is cross-reactive with the class II negative tumor. Inasmuch as the transfected MHC class II gene product is not functioning as a target molecule for autologous tumor rejection, the improved immunogenicity of the Sal/Ak cells is probably due to stimulation of a tumor-specific Th cell population. The increased immunogenicity of Sal/Ak cells is, therefore, probably the result of direct presentation of Sal tumor-associated Ag in the context of tumor cell MHC class II molecules to Th lymphocytes. These studies demonstrate that induction of tumor cell MHC class II Ag expression is a potential strategy for tumor-specific immunotherapy, and suggest that tumor immunity may be enhanced by improved Th cell generation. PMID- 2332640 TI - A study of the protozoa associated with some harmful insects in the local environment. AB - The present study includes finding resulting from examination of three species of harmful insects, Periplaneta americana, Schistocerca gregaria and Anacanthoterms ochraceus, collected from six cities in the Central Region of Saudi Arabia. Two species of septate gregarines of the genus Gregarina Dufor, were found G. blattarum (Siebold) from mid gut of P. americana and G. rigida from gut of S. gregaria, also six species of Mastigophora in gut of white ant A. ochraceus, Trichonympha campanula, Spirotrichonympha sp., Holomastigoides hartmanni, Rostronympha magna Monocercomonas axostylis and an unidentified species. The seasonal intensity of these Protozoa and percentage of infection together with informations about the holotype materials are included. At present the holotype materials are deposited at the department of Zoology, Girls College of Education, Riyadh, Saudi Arabia. PMID- 2332641 TI - Seasonal variation and incidence of Stictodora tridactyla in fish from lake Manzala. AB - Stictodora tridactyla encysted metacercariae were detected in Mugil and Tilapia collected only from brackish water fish from lake Manzala. The prevalence and intensity of encysted metacercariae were higher in summer than in winter. PMID- 2332642 TI - Parasites and predators associated with blow flies and flesh flies in Cairo region. AB - The results indicated that five species belonging to order Coleoptera and five parasite species belonging to order Hymenoptera were associated with blow fly and flesh fly larvae and pupae in Cairo region during the survey period. PMID- 2332643 TI - A study on intestinal helminths causing anaemia in man in Cairo. AB - Haematological and biochemical studies were done for 50 urban and rural Egyptians, from Cairo, suffering from A. duodenale, A. lumbricoides, E. vermicularis, H. nana, S. mansoni and T. saginata. Anaemia of varying degree was noticed in all cases. The lowest Hb% and hematocrit value were found in cases of ancylostomiasis. The blood films of the same patients showed severe hypochromia compared with the other parasitic infections. The highest figure for eosinophilia was found in ancylostomiasis (29%) followed by S. mansoni (14%). Total blood protein was normal in all cases, however, 2 cases of S. mansoni showed higher values (8.5 gm% and 8.9%). Generally blood cholesterol and blood urea showed no deviation from normal as regards all patients. PMID- 2332644 TI - Comparison between parasitological and serological techniques in assessment of schistosomiasis prevalence. AB - The prevalence of schistosomiasis serologically based on detection of anti soluble egg antigen (SEA)--IgM and/or IgG by ELISA technique was 68% of 380 cases, and 52.7% of 148 cases by stool examination. The serological technique seems to be more sensitive and able to detect early infection as well as detection of ectopic infection. PMID- 2332645 TI - The role of single sample detection of specific anti-Toxoplasma IgM in accurate evaluation of seroconversion during acquired toxoplasmosis. AB - Specific IgM anti-Toxoplasma antibodies were sought in 94 serum samples by means of D.S. IgM ELISA. These antibodies were detected in all cases of acute toxoplasmic lymphadenopathy, but up to 13 months from onset of symptoms and in out of 20 patients with chronic toxoplasmosis and in one out of 20 seronegative individuals. They were neither detected in samples from 4 infants with high IgG IFAT titres associated with hydrocephalus and cerebral calcification, nor in samples from patients containing rheumatoid factors and those with lymphoma or infectious mononucleosis. Thus the detection of IgM antibodies seems non decisive mean for identifying infected infants and for determination of the exact date of acquiring the infection. PMID- 2332646 TI - Morphogenesis of the flagellum and its associated structures in Leishmania. AB - Electron microscopic study of the flagellar apparatus of promastigote and amastigote forms of Leishmania revealed major differences. Promastigotes were characterized by possessing a paraxial rod with a well developed lattice-like complex alongside the emerging axoneme enclosed within the flagellar sheath. The latter was anchored to the protozoan plasma membrane by focal or spot-like macular desmosomes at the emergence site. With cytodifferentiation to amastigotes there was a notable reduction in the axonemal size and its microtubular elements, absence of paraxial rod and a remarkable binding of the endocellular flagellum to its pocket through dense zonular desmosomal adhesions. PMID- 2332647 TI - Methacrylate embedding as a new technique for histopathological studies on the effect of Bacillus thuringiensis against Culex pipiens. AB - Studies on the pathogen Bacillus thuringiensis in Egypt and its possible role as a biological control agent have been reviewed. More emphasis in research was given to some lepidopterous cotton pests and few other species. Histopathological changes in B. thuringiensis treated larvae could be observed in the midgut. The methacrylate embedding technique achieved satisfactory results in concern of better preservation of histological fine details. PMID- 2332648 TI - A study of adhesive organelles of Giardia intestinalis. AB - This study revealed that the adhesive disc of Giardia lamblia trophozoite has different forms. The anterior limitation of the ventrolateral flange to the adhesive disc and its flexibility suggests its participation in the mechanism of attachment of the trophozoite. Normal intestinal crypts promote attachment of Giardia trophozoite by providing a passive mechanical barrier against the main peristaltic flow. The mechanism of attachment is described in details. PMID- 2332649 TI - An electron microscope study on spermatogenesis in Hymenolepis nana. AB - Only on the basis of nuclear size, spermatogonia can be easily identified by their relatively large prominent nuclei. Further meiotic division occur resulting in primary spermatocytes. The nuclei become smaller, placed peripherally forming the spermatids. A membrane-bound clefts develop in the cytoplasm in the region of spermatid nuclei and that such clefts eventually enclose the elongated nuclei to become the plasma membrane of the sperm. There is a common general pattern of spermatogenesis in cestodes which follows the pattern typical of the platyhelminthes. PMID- 2332650 TI - Serum immunoglobulins and complement in patients suffering from amoebic liver abscess. AB - Immunoglobulins IgG, IgM & IgA and complement C3 were studied in 24 patients suffering from amoebic liver abscesses (ALA) before and two months after therapy. The results were compared with those of 12 healthy controls. IgG and IgA showed significant higher level in ALA patients than the normal controls, P less than 0.001 and P less than 0.01 respectively. IgM level was also higher than the normal controls but the difference was insignificant. Follow up of these Igs showed marked drop two months after therapy. C3 level was found statistically higher in ALA before therapy than that of the normal controls and that of patients two months after therapy. Correlation between C3 level and the size of the abscess showed that its level was statistically higher in large abscesses P less than 0.05. PMID- 2332651 TI - On the specificity of the indirect haemagglutination in diagnosis of visceral leishmaniasis. AB - Human sera were collected from parasitologically proven cases of filariasis, strongyloidiasis, hymenolepiasis and ascariasis. Antibodies against these parasites cross react in the indirect haemagglutination for the antileishmanial antibodies at dilution up to 1:128. The diagnostic titer should be raised to 256 in order to increase the specificity of the test in areas where such parasites occur. PMID- 2332652 TI - Cell-mediated immune response in experimental infection with H. heterophyes. AB - Experimental infection of puppies with Heterophyes heterophyes was associated with marked cell-mediated immune response that manifested itself by increase of T cell count and leucocyte migration. The degree of cell-mediated immune response was inversely proportional to the intensity of infection. The significance of the results was discussed. PMID- 2332653 TI - The toxic pathophysiology of retinol hypervitaminosis and norethisterone enantate in rats. AB - The use of the long acting contraceptive was accompanied by clinically overt toxic manifestations on the liver, glucose tolerance, in addition to the danger of carcinogenicity. Also chronic hypervitaminosis "A" leads to a variety of toxic manifestations of obscure mechanism. The objective of this experimental work was directed to study the toxicity of the isolated and combined augmented doses of the two therapeutic agents on the female albino rat. The results of the present study evidenced that the long acting contraceptive norethisterone enantate is potentially hepato- and nephro-toxic. More damage to the liver; and luteinization of theca and stroma cells of the ovaries occurred as a result of retinol hypervitaminosis. The brunt of toxicity and damage on the test organs after coadministration of both chemicals proved to be synergetic except on the ovarian tissues. PMID- 2332654 TI - Mosquitoes of the genus Culex in the Suez Canal Governorates. AB - Mosquitoes are among the most annoying and important vectors of human and animal diseases as malaria, filariasis, yellow fever, rift valley fever...etc. In this paper, it was aimed to study the present status of species of genus Culex in the Suez Canal Governorates after the reconstruction and developmental projects. Five species of Culex were identified: C. pipiens, C. univittatus, C. antennatus, C. poicilipes and C. pusillus. The latter species was represented by two specimens. C. pipiens was the commonest species both indoors and outdoors. C. antennatus and C. poicilipes were found only outdoors. C. pipiens was found all the year round particularly in Spring. Other species were found in Spring and Autumn, except C. antennatus which was found in Summer as well. The results were discussed on the light of work done before. PMID- 2332655 TI - In vitro study on generation time (G) of Trichomonas vaginalis. AB - 31 strains of T. vaginalis were isolated from female patients attending venereal diseases clinic, Middlesex Hospital, London. Cloned organisms were studied in vitro for generation time (G). According to generation time T. vaginalis strains were divided into three different groups: slow, medium and fast grow. PMID- 2332656 TI - Endogenous stages of Eimeria arvicanthi infecting the field rat Arvicanthis niloticus niloticus from Egypt. AB - The endogenous stages of Eimeria arvicanthi were studied after experimental infection with pure strain in the rat Arvicanthis n. niloticus. The prepatent period was 5 days, while the patent period extended to the 11th day p.i. Two asexual generations were determined in the epithelial cells of the upper part of the colon, while the sexual one was found in the crypts of Lieberkuhn. Schizonts of the 1st generation were found 60 hrs p.i., measuring 9 X 4 microns and contained 4-8 merozoites, however those of the 2nd generation were found at 96 hrs p.i., measured 14 X 10 microns and contained 8-12 merozoites. Gamonts were firstly recorded at 108 hrs p.i., after growth they differentiated and gave rise to gametes. Macrogametes were 19 X 17 microns with large nuclei and wall-forming bodies in their cytoplasm. Microgamonts (14 X 11 microns) were irregular in shape and after many nuclear divisions produce many microgametes. Eimeria arvicanthi was pathogenic and about 60% of the experimentally infected rats with 3-5 X 10(5) sporulated oocysts were died till the 9th day p.i. PMID- 2332657 TI - The effect of some anticoagulants against three commensal rodents under laboratory conditions. AB - Eight anticoagulant rodenticides were used against Rattus norvegicus, R. r. frugivorous and Muss musculus. Phenal proved to be the most suitable against R. norvegicus, while Redentin 75 was less effective. However, males accepted Super Caid as bait. On the other hand, Klerat Super was more effective than Storm against R. r. frugivorous and M. musculus, in choice feeding and V.V. in no choice feeding. It was concluded that more than one anticoagulant rodenticide being recommended with interval between application in a large rodent infested area. PMID- 2332658 TI - Effect of gamma irradiation on the rate of cyst development of E. granulosus larvae in Swiss albino mice. AB - White albino mice Mus Musculus albinus were intraperitoneally inoculated with aseptical normal and gamma irradiated protoscolices of E. granulosus at dose level of 40, 60, 80 and 100 Kr. Mice, either normaly infected or infected with irradiated protoscolices and sacrificed at intervals of 4, 6, 8, 10, 12, 14 and 16 weeks, showed a marked increase in the percentage of cyst number in the liver than in the peritoneal cavity or around spleen, although by increasing the dose level to 100 Kr. no cyst were developed around the spleen. Meanwhile the % of developing cyst in the peritoneal cavity was time and dose level dependent. The mean cyst diameter showed a progressive increase with the increase of infection time and a successive decrease by increasing the dose level of gamma irradiation. An increase in the number of cyst was observed particularly in normal mice where a marked increase was noted on the 8th week post infection while a successive decrease in the mean number of cyst was observed by increasing the dose level of gamma irradiation. PMID- 2332659 TI - Some histological studies on the oesophagus of the Nile fox (Vulpes Vulpes aegyptiaca). AB - This work was carried out on eight foxes. The results showed that, the lining epithelium is of stratified squamous non-keratinized type which abruptly changed into glandular simple columnar epithelium. The lamina muscularis mucosa is in the form of small scattered strands of smooth muscle fibers in the cranial and middle parts and formed a continuous layer in the caudal part near the cardia. The submucosal glands are well developed and extend along the whole length of the oesophagus till reached slightly below the cardiac region of the stomach. They were mainly of mucous acini with few serous one. The glandular mucous acini were alcianophilic. The tunica muscularis externa is of skeletal muscles along the whole length of the oesophagus except just before the cardia by 1.5 cm, the tunica muscularis are formed from mixture of smooth and skeletal muscle fibres. PMID- 2332660 TI - On the characterization of the flagellate parasite of uncertain identity from the brown rats and dogs in Egypt. PMID- 2332661 TI - Phlebotomus papatasi a possible vector of cutaneous leishmaniasis, in Khartoum, Sudan. PMID- 2332662 TI - Serological and parasitological examination of some patients with manifestations suggestive leishmaniasis. AB - The present study was designed to search for visceral leishmaniasis (VL.) in adult population in the Nile Delta. For this purpose: Fifty patients with splenomegaly and/or hepatosplenomegaly were chosen upon clinical grounds with special consideration of clinical manifestations suggestive of the disease. Both indirect haemagglutination test (IHAT) and dot-Enzyme Linked Immuno Sorbent Assay (dot-ELISA), were positive for VL. antibodies in 3% of the patients. Bone marrow examination (smear and culture) revealed negative results in all patients who gave serological reactions. The results were discussed. PMID- 2332663 TI - On the serodiagnosis of leishmaniasis in Egypt. PMID- 2332664 TI - Ultra structural studies of the surface of Hymenolepis nana by scanning and transmission electron microscopy. AB - Scanning electron microscopy of the surface of Hymenolepis nana indicated that dense populations of microtriches occur on scolex proper, suckers and strobila, with an average density of 20/micron2. The excellent preservation of microtriches proves the efficacy of the critical point drying method for preparing cestodes for study of SEM. The cytological structure of the tegument of H. nana corresponds in general to that of other tapeworms. PMID- 2332665 TI - Parasitic infections and haemoglobin level among school children of different socioeconomic classes in Abha, Saudi Arabia. AB - A total of 717 school children from Abha region, from upper, middle and lower social classes (182, 405 & 130 respectively), were examined for parasitic infections and haemoglobin level. Giardia lamblia was found to be the most common intestinal parasite among children of all classes, Entamoeba histolytica followed among children of middle class, and Hymenolepis nana among those of lower one. Anaemia was more prevalent among parasitically infected children particularly the multi-infected ones of the lower social class. PMID- 2332666 TI - Effect of unfed female weight on the biology of Hyalomma (Hyalomma) dromedarii Koch (Acari: Ixodidae). AB - Unfed female Hyalomma (Hyalomma) dromedarii Koch in 3 different weight groups of 2.4-5.0, 5.3-10.0 and 10.3-14.5 mg, respectively, were investigated for the effect of unfed female weight (UFW) on certain biological parameters. The results showed that the correlation between UFW and the duration of the feeding, preoviposition and oviposition periods varies greatly among the different weight groups and the pooled data. Engorged female and egg mass weights were strongly correlated with UFW of the smallest female group, and the degree of correlations decreased with increase of UFW in the other weight groups. The residual female weight (after oviposition cessation) was strongly correlated with UFW for all weight groups. The egg mass weight was strongly correlated with engorged female weight and the conversion efficiency index was similar for all weight groups. The oviposition pattern for the different weight groups and pooled data appeared similar but peak oviposition values were lacking for the largest female group. The results obviate the necessity of accurate random sampling of the entire tick population or specifying the UFW when studying ixodid biology. PMID- 2332667 TI - A preliminary study of liver functions in heterophiasis. AB - The values of serum aspartate transaminase SGOT and serum alanine transaminase SGPT were observed to elevate in pigeons experimentally infected with Heterophyes heterophyes. Histopathologically the liver showed congestion, fatty infiltration and periportal round cell infiltration. Kupffer cells showed proliferation. PMID- 2332668 TI - Echinococcosis in camels as revealed by indirect haemagglutination test in Belbas. AB - This study aimed to estimate the prevalence of Echinococcus antibodies in camels using the indirect haemagglutination test (I.H.A.T.). Out of 100 camels, 27 camels were seropositive. PMID- 2332669 TI - Effect of some drugs on some histopathological and immunological aspects of experimental trichinosis in albino rats. AB - The present work is concerned with study of the effects of praziquantel, thiabendazole, mebendazole, cyclophosphamide and cortisone on histopathology of the small intestine (during intestinal phase) and skeletal muscles (during muscular phase), in addition to T. lymphocytes count and serum IgG estimation in experimental trichinosis in albino rats. Praziquantel has no effect on the histopathology of small intestine or skeletal muscles. Thiabendazole and mebendazole treatment resulted in complete eradication of Trichinella spiralis worms of small intestine and marked reduction of larval infection (mild infection) of skeletal muscle. Praziquantel, thiabendazole and mebendazole did not affect significantly the T. lymphocytes count of the host during the intestinal phase. Cyclophosphamide and cortisone suppressed the cellular immunity (T. lymphocytes) and accordingly enhanced the parasitic infection in histopathology of both phases. All the drugs tested induced significant reduction of T. lymphocytes in muscular phase (which may be due to parasitic infection itself) and insignificant effect on IgG level in both phases. PMID- 2332670 TI - [Quenching effect and analysis of cell proliferation in dual-laser flow cytometry with human endometrial adenocarcinoma cells in vitro]. AB - We analyzed the characterization of DNA synthesized cells (S phase cells) in the proliferation. It is important that the fixation and cell cycle time of S phase cells and DNA qualitative changes, etc., be examined. We used the dual-laser FCM system of the Los Alamos National Laboratory in New Mexico and analyzed the cell cycle, especially changes in S phase cells both quantitatively and qualitatively. By the bromodeoxyuridine (BrdU)/Hoechst Quenching effect, we could detect differences in electric signals by adopting the differential fluorescence correction method. (1) The effects of sodium butyrate in gene expression were dose-dependent at human endometrial adenocarcinoma cells. (2) After double staining with Mithramycin and Hoechst33342, S phase cells incorporating BrdU under quenching gave from linear relative to arched bivariate contour histograms. (3) At 24 hours G1 phase synchronization of SB 1,3 and 5mM appeared in slow cycling cells after BrdU was added. These results suggest that the effect of sodium butyrate in human endometrial adenocarcinoma cells might be understood not only from the quantitative change, but also by the qualitative change in S phase cells. PMID- 2332671 TI - [Detection of HTLV-I genome in infants born to HTLV-I seropositive mothers by polymerase chain reaction]. AB - We developed a new method to detect human T cell leukemia virus type I (HTLV-I) provirus by amplifying the pX region of the HTLV-I genome by means of the polymerase chain reaction (PCR) method. This new method was used to examine babies delivered by HTLV-I carrier women for HTLV-I vertical transmission. It was found that intra-uterine infection with HTLV-I can occur, though rarely, and some babies carry HTLV-I provirus despite their negative response to HTLV-I antibody, and, noticeably, some of the babies found negative by the conventional antigen detection method may be positive when tested by the PCR method. It was also confirmed with the PCR method that the incidence of vertical transmission of HTLV I can be reduced to about 1/5 by replacing breast feeding with bottle feeding and frozen mother's milk feeding. It was also found that vertical transmission of HTLV-I can occur at high incidence rates even when the duration of breast feeding is 3 months or less. PMID- 2332672 TI - [Stump recurrence after radical hysterectomy for patients with uterine cervical cancer]. AB - Of a total of 1,025 cases of radical hysterectomy for histological squamous cell carcinoma (543 stage I cases and 482 stage II cases), we examined 50 cases of recurrence of the carcinoma (4.9 percent; 24 stage I cases and 26 stage II cases) at the site of the vaginal stump. The percentage of recurrence at the site of the vaginal stump was significantly higher in stage I and stage II cases, in which metastases to the lymph nodes or vascular invasion was observed (p less than 0.01). The length of vagina excised during the radical hysterectomy was measured and its relationship to recurrence at the site of the vaginal stump was investigated. In stage I cases that did not exhibit metastases to the lymph nodes, the shortest vaginal length excised in cases with a positive recurrence at the site of the vaginal stump was 2.5 +/- 0.9 cm; the shortest vaginal length in cases with a negative recurrence at the site of the vaginal stump was 1.8 +/- 0.8 cm. A significant difference (p less than 0.05) was observed between them. Furthermore, in stage I cases with no metastases to the lymph nodes, one recurrence at the site of the vaginal stump was observed when the vaginal length excised was 3 cm. In stage I cases with metastases to the lymph nodes and in stage II cases, no significant difference was discovered between the length of vagina excised in cases with positive and those with negative recurrences of the carcinoma at the site of the vaginal stump. PMID- 2332673 TI - [Effects of maternal exercise using bicycle ergometer on maternal heart rate, blood pressure, oxygen consumption and fetal heart rate]. AB - The effects of maternal exercise on pregnant women and fetal well-being are largely unknown. Forty-eight pregnant women between 16 and 39 weeks' gestation were exercised on a bicycle ergometer. We studied the oxygen consumption, blood pressure, maternal and fetal heart rate (FHR) at rest, during and after the exercise. The mean maternal heart rate and blood pressure were increased to 166.1 +/- 12.2/min (mean +/- S.D., n = 48) and 161.1 +/- 20.1/82.7 +/- 15.2 mmHg, respectively, at maximal exercise. The absolute oxygen consumption (1/min) was increased with advancing pregnancy at rest and maximal exercise, but the functional oxygen consumption (ml/kg/min) was not changed during pregnancy. The mean FHR was increased about 4 and 9 bpm in the 2nd and 3rd trimesters, respectively. Abnormal FHR patterns after the exercise were observed in 8 cases (16.7%), mild tachycardia: 6 cases, deceleration: 2 cases. Increasing the maternal heart rate at maximal exercise, increased the frequency of the abnormal FHR pattern. When the maternal heart rate was below 160/min, there was no abnormal FHR pattern. These results suggest that several medical checks should be done not only for the mother but also for her fetus during exercise and the maternal heart rate should not exceed 160/min. PMID- 2332674 TI - [A study of amplifications of myc gene (c-myc and N-myc) in human ovarian cancer]. AB - Amplifications of myc oncogenes (c-myc, N-myc) were studied by Southern blot hybridization methods in ovarian cancers. Fourteen cases were primary ovarian cancers and one case was metastatic ovarian cancer. Primary and metastatic foci of three primary ovarian cancers were compared. A serous adenocarcinoma had a c myc gene amplification more than 10 fold without N-myc gene amplification. This case also had an amplification in other c-myc probes with upper and down streams of the second exon. The results suggested that this case had c-myc gene expression. One of these cases had 5 fold amplification of the metastatic focus compared with the primary focus. The amplified c-myc gene did not show relations among clinical courses, prognosis and histologies. PMID- 2332675 TI - [Enzymatic colorimetric determination of phosphatidylglycerol in amniotic fluid]. AB - Although the concentration of phosphatidylglycerol (PG) in amniotic fluid is generally considered indicative of fetal lung maturity, the thin layer chromatographic techniques currently used to measure this concentration have been criticized. We have investigated a highly sensitive method for determining amniotic fluid phosphatidylglycerol by using L-glycerol-3-phosphate (G-3 P).dihydroxyacetone phosphate enzymatic cycling reaction and relate this finding to the assessment of fetal lung maturity. Under the assay conditions described above, glycerol oxidase eliminates endogenous glycerol in the amniotic fluid prior to analysis. The subsequent enzymatic reaction sequence involves conversion of phosphatidylglycerol to G-3-P by phospholipase D and glycerol kinase in the presence of ATP. G-3-P is subsequently determined with amplification by enzymatic cycling reaction of G-3-P oxidase and G-3-P dehydrogenase in the presence of oxygen and NADH2. The absorbance is measured at 542 nm. The quantitation of phosphatidylglycerol is linear over the concentration range of 0-20 microM and the detection limit is 0.4 mumol/l. Within run CV's were found to be 1.25% at 13.8 mumol/l (n = 7) and 3.0% at 4.2 mumol/l (n = 7). The results obtained from 48 samples using this procedure, revealed that a level less than 1.0 mumol/l of PG persisted until the 29th week of gestation. A gradual increase in PG (more than 1.0 mumol/1) beginning in the 30th week of gestation was observed. A sharp increase in PG was also found in the 37th week of gestation. PMID- 2332676 TI - Sialates and negative charge on the surface of syncytiotrophoblastic cells of full-term placentae in toxemic patients. AB - In the syncytiotrophoblastic surface of the toxemic full-term placentae, the sialates and their consequent negative charging were studied by both electron microscopic histochemistry (Ferritin method) and Western blot analysis. Evidence is presented showing (1) that the reactions with both the ferritin labelled Limulus Polyphemus Agglutinin (LPA-ferritin), specific to sialates, and the cationized ferritin, specific to a negative charge, decrease in the specimens of toxemic placentae, (2) that the density of sialates in placentae of severe gestational proteinuria or/and hypertension is statistically lower than that of severe gestational edema, and (3) that there is no difference between the blotted bands in normal placentae and toxemic ones regardless of the severity of the toxemia. These results indicate that the reduction of the surface negative charging is demonstrated in toxemic syncytiotrophoblasts and appears to be secondary to the decrease in the amount of sialate. PMID- 2332677 TI - Modulation of human endometrial stromal cell morphology and cell growth on various types of collagen substrates in vitro. PMID- 2332678 TI - [The present situation of AIDS in Japan and preventive measures]. PMID- 2332679 TI - [Diagnosis and treatment of HTLV-I associated myelopathy]. PMID- 2332680 TI - [The present situation of Legionnaires' disease in Japan and countermeasures]. PMID- 2332681 TI - [Epidemiologic study and diagnosis of endemic Rickettsia infections of tsutsugamushi and spotted fever]. PMID- 2332682 TI - [Clinical and epidemiologic study of pulmonary tuberculosis]. PMID- 2332683 TI - [Prevention and drug therapy of methicillin resistant Staphylococcus aureus infections]. PMID- 2332684 TI - [Diagnosis and prevention of cross infection]. PMID- 2332685 TI - [Hypertension due to endocrinologic disorders]. PMID- 2332686 TI - [Evaluation of disease activity in patients with systemic lupus erythematosus and administration of adrenal cortex steroids]. PMID- 2332687 TI - [Diagnosis and treatment of hepatitis]. PMID- 2332688 TI - [Enterohepatic circulation of bile acids and abnormalities]. PMID- 2332689 TI - [Degenerative nerve diseases]. PMID- 2332690 TI - [Emergency treatment of serious conditions in arrhythmia]. PMID- 2332691 TI - [Progress in diagnosis and treatment of virus diseases]. PMID- 2332692 TI - [Clinical administration of antibiotics]. PMID- 2332693 TI - [Intractable airway infection and treatment]. PMID- 2332694 TI - [Recent progress in the treatment of chronic respiratory failure]. PMID- 2332695 TI - [Diagnosis and treatment of anemia]. PMID- 2332696 TI - [Drug therapy of leukemia and malignant tumors]. PMID- 2332697 TI - [Diagnosis of hemorrhagic tendency]. PMID- 2332699 TI - "Health access America"--strong medicine! PMID- 2332698 TI - [Treatment and diagnosis of glomerulonephritis and nephrotic syndrome]. PMID- 2332700 TI - An update on chronic sinusitis. AB - The management of chronic sinus disease has been revolutionized by the application of computed tomographic (CT) imaging and rigid endoscopes in diagnostic evaluation and surgical treatment. These diagnostic advances have led to a better understanding of sinus pathophysiology and the development of more rational surgical treatment. Obstruction of mucociliary drainage in the anterior ethmoid sinus-middle meatus region (ostiomeatal complex) is now understood to be the cause of chronic symptomatic sinus disease. Involvement of the maxillary or frontal sinus is usually secondary to disease in the ostiomeatal complex. Three cases are presented to illustrate the use of CT scanning and nasal endoscopy in the evaluation of chronic sinusitis. Precise identification and correction of ostiomeatal complex obstruction with endoscopic surgical techniques has proven efficacious and is associated with minimal patient morbidity. Endoscopic sinus surgery is emerging as the treatment of choice for medically unresponsive chronic sinus disease. PMID- 2332701 TI - JCMS Outreach Program establishes the John H. Morgan Center for the Homeless. PMID- 2332702 TI - Putting something back in the well. PMID- 2332703 TI - Evolutionary optimization and neural network models of behavior. AB - One of the main challenges to the adaptionist program in general and the use of optimization models in behavioral and evolutionary ecology, in particular, is that organisms are so constrained by ontogeny and phylogeny that they may not be able to attain optimal solutions, however those are defined. This paper responds to the challenge through the comparison of optimality and neural network models for the behavior of an individual polychaete worm. The evolutionary optimization model is used to compute behaviors (movement in and out of a tube) that maximize a measure of Darwinian fitness based on individual survival and reproduction. The neural network involves motor, sensory, energetic reserve and clock neuronal groups. Ontogeny of the neural network is the change of connections of a single individual in response to its experiences in the environment. Evolution of the neural network is the natural selection of initial values of connections between groups and learning rules for changing connections. Taken together, these can be viewed as "design parameters". The best neural networks have fitnesses between 85% and 99% of the fitness of the evolutionary optimization model. More complicated models for polychaete worms are discussed. Formulation of a neural network model for host acceptance decisions by tephritid fruit flies leads to predictions about the neurobiology of the flies. The general conclusion is that neural networks appear to be sufficiently rich and plastic that even weak evolution of design parameters may be sufficient for organisms to achieve behaviors that give fitnesses close to the evolutionary optimal fitness, particularly if the behaviors are relatively simple. PMID- 2332704 TI - Analysis of a disease transmission model in a population with varying size. AB - An S----I----R----S epidemiological model with vital dynamics in a population of varying size is discussed. A complete global analysis is given which uses a new result to establish the nonexistence of periodic solutions. Results are discussed in terms of three explicit threshold parameters which respectively govern the increase of the total population, the existence and stability of an endemic proportion equilibrium and the growth of the infective population. These lead to two distinct concepts of disease eradication which involve the total number of infectives and their proportion in the population. PMID- 2332705 TI - On transient effects in the HIV/AIDS epidemic. AB - During the initially exponential spread of the human immunodeficiency virus (HIV- the causative agent of AIDS) the growth rate of the number of AIDS cases decreased from plus infinity to the growth rate of HIV infections. A sensitivity analysis shows that for all reasonable values of the parameters of the HIV epidemic (incubation period, initial doubling time, etc.) the effect of this positive transient becomes negligible when the annual number of AIDS cases reaches a few dozen. Necessary and sufficient conditions are given for the growth rate of the number of AIDS cases to be monotonically decreasing during the positive transient. A mildly pathological density function for the incubation period of AIDS provides an example of a growth rate of AIDS that does not decrease monotonically, even though HIV is spreading exponentially. A negative transient occurs when the growth rate of HIV begins to decrease. In this context a somewhat surprising result emerges under the assumption that the growth rate of HIV is non-increasing: the growth rate of AIDS is at all times larger than the growth rate of HIV. A logistic HIV epidemic illustrates this result, and implications for the growth of the HIV epidemic in the United States and Europe are discussed. In particular, it is shown that the positive transient must have passed by 1982 in the United States and by 1986 or 1987 for the five European countries with the largest caseloads. PMID- 2332706 TI - On the classification of regular systems of inbreeding. AB - Regular systems of inbreeding are defined as those with discrete, nonoverlapping generations and with the same number of individuals and mating pattern in every generation. Given the number of individuals in a generation, there are many possible regular mating systems. A notion of when two such mating systems are equivalent is introduced, and several necessary conditions are given for such an equivalence. The use of these conditions is illustrated for N = 2, 3, 4 and 5 individuals, and a complete enumeration has been found for these cases: the numbers of inequivalent mating systems are 1, 5, 57 and 858, respectively. The maximal eigenvalue of the matrix q that specifies the recursion relations satisfied by the probabilities of identity have also been found for these cases. For N = 3 and 4 (and 2 trivially), circular mating gives the slowest rate of approach to genetic uniformity of those systems that do evolve to uniformity, but for N = 5 there are two other mating systems that have a slower rate of convergence, and for N = 6 partial results show that there are many such examples. PMID- 2332707 TI - Superposition of modes in a caricature of a model for morphogenesis. AB - In a model proposed for cell pattern formation by Nagorcka et al. (J. Theor. Biol. 1987) linear analysis revealed the possibility of an initially spatially uniform cell density going unstable to perturbations of two distinct spatial modes. Here we examine a simple one-dimensional caricature of their model which exhibits similar linear behaviour and present a nonlinear analysis which shows the possibility of superposition of modes subject to appropriate parameter values and initial conditions. PMID- 2332708 TI - Mathematical analysis of multisolute renal flow in a single nephron model of the kidney. AB - A single nephron model, which includes the Bowman's space, Cortical interstitium, and Pelvis as well-stirred baths, is investigated. A boundary value problem, which allows for pelvic reflux, is established for the fluid-multisolute flow in the nephron. The implicit function theorem is used to establish the existence and uniqueness of a solution of the boundary value problem for the case of small permeability coefficients and transport rates. PMID- 2332709 TI - Maintenance of polygenic variation through mutation-selection balance: bifurcation analysis of a biallelic model. AB - Biallelic models which ignore linkage disequilibrium have been used to study variability maintained by mutation in the presence of Gaussian stabilizing selection. Recent work of Barton (1986) showed that these models have stable equilibria at which the mean phenotype differed from the optimum, and that the variability maintained at such equilibria would be higher than at the symmetric equilibria calculated by Bulmer (1980) and others. Here I determine the bifurcation structure of this model, and confirm and extend Barton's results. The form of the bifurcations gives information about the domains of attraction of various equilibria, and shows why the nonsymmetric equilibria may not be observed. The techniques may prove useful in the analysis of other population genetic models. PMID- 2332710 TI - On Lienard's equation and the uniqueness of limit cycles in predator-prey systems. AB - We study a system of ODE's modelling the interaction of one predator and one prey dx/dt = xg(x) - yp(x), dy/dt = gamma y[- delta - nu y - alpha y2 + h(x)]. This system defines a two-species community which incorporates competition among prey in the absence of any predators as well as a density-dependent predator specific death rate. This system is investigated under ecologically natural regularity conditions and assumptions on g, p and h to ensure the existence and uniqueness of limit cycles. The proof uses the standard Hopf-Andronov bifurcation theory and the technique of Lienard's equation. PMID- 2332711 TI - Prediction of temperature profiles in the human skin and subcutaneous tissues. AB - Exact mathematical solutions in terms of confluent hypergeometric and Airy's functions are obtained to study the steady state temperature distributions in human skin and subcutaneous tissues (SST). It is assumed that the skin is exposed to an air environment and heat transfer from the skin occurs by convection, radiation and evaporation. A mathematical model of the SST, accounting for heat conduction, perfusion of the capillary beds and metabolic heat productions of the dermis and subcutaneous tissues, has been solved to obtain interface temperatures for a wide range of environmental temperatures, rates of evaporation of sweat, wind speeds and relative humidities. The solutions provide inter-relationships between interface temperatures, thermal conductivities, metabolic heat production, blood perfusion, thicknesses of various layers of SST and ambient temperature. PMID- 2332712 TI - AMA-ERF--ensuring quality medical education. PMID- 2332713 TI - Mobile medical facilities and CONs: maneuvering mobile medicine through a stationary statutory scheme. PMID- 2332714 TI - Merkel cell tumor: a review of the literature. PMID- 2332715 TI - Plasma clearance of chicken and human insulin-like growth factor-I and their association with circulating binding proteins in chickens. AB - We have investigated the clearance of 125I-labelled chicken and recombinant human insulin-like growth factor-I (IGF-I) from the circulation of chickens as well as the role that IGF-binding proteins play in this process. Analysis of plasma samples by high-performance liquid chromatography (HPLC) neutral gel permeation on a TSK G3000SW column indicated that the i.v. injected radioactivity was rapidly partitioned between at least three pools. Most of the radioactivity occurred in a complex with binding protein(s), while smaller amounts of radioactivity chromatographed in the free IGF-I peak or appeared as low molecular weight degradation products. The labelled chicken and human IGF-I were rapidly cleared during the first 90 min. The calculated half-life for total labelled IGF I during this period was 54 min for the chicken tracer and 33 min for the human tracer. The clearance was monitored for 10 h during which the human tracer continued to be cleared more rapidly than the chicken tracer. The proportion of radioactivity appearing as low molecular weight degradation products increased with time. Acid gel permeation and reverse-phase HPLC of the binding protein associated radioactivity demonstrated that the labelled IGF-I bound was intact IGF-I. Sephadex G-200 gel permeation chromatography of chicken plasma samples at pH 7 x 4 showed that the binding protein complex labelled in vivo with chicken IGF-I tracer had a molecular mass of 55 kDa. Furthermore, the tracer associated with the binding protein coeluted with the major peak of endogenous IGF-I, suggesting that the tracer was bound to the physiologically relevant binding protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332716 TI - The depletion of plasma prolactin by pantethine in oestrogen-primed hyperprolactinaemic rats. AB - Pantethine was investigated for its potential to deplete prolactin in the plasma and pituitary cells of oestrogen-primed hyperprolactinaemic rats. This compound has been used in the past to deliver cysteamine systemically, through its congener pantetheine, a metabolic precursor for cysteamine. Cysteamine itself, specifically reduces plasma and pituitary prolactin. The addition of pantethine (2-10 mmol/l) to the media of isolated pituitary cells over 4 h did not appreciably alter the intracellular content of immunoreactive prolactin. Moreover, oral administration of pantethine at 0.5 and 1.0 g/kg body weight did not influence the concentration of immunoreactive plasma prolactin. However, the concentration of plasma prolactin fell by 48 and 67%, when pantethine was injected i.p. at 0.5 and 1.0 g/kg body weight, after 4 h. Intravenous administration of pantethine resulted in even greater losses of prolactin, in the order of 50 and 81% depletion for 0.5 and 1.0 g/kg body weight respectively and within 2 h of administration. However, cysteamine was found to be more efficacious than pantethine on a molar basis with regard to depleting the plasma concentration of prolactin in hyperprolactinaemic rats. PMID- 2332717 TI - Induction of lactogenic receptors in liver of hypophysectomized rats treated with bovine growth hormone-monoclonal antibody complexes. AB - Male hypophysectomized rats treated with bovine (b)GH-monoclonal antibody complexes showed enhanced weight gain compared with animals treated with bGH alone over a 12-day treatment period. Liver microsomes prepared from animals showing enhanced weight gain exhibited increased specific binding of human (h)GH. Studies on the specificity of these binding sites showed that they were lactogenic, 125I-labelled hGH being displaced by ovine prolactin, but not by non mammalian growth hormones. In this respect they were similar to lactogenic binding sites in the liver of pregnant rats. Monoclonal antibodies to hGH blocked binding to lactogenic receptors to different extents. The pattern of such inhibition was similar, but not identical, for the receptors induced in hypophysectomized rats and those from pregnant rat liver. The evidence available suggests that the lactogenic receptors induced by bGH-monoclonal antibody complexes are not directly involved in the enhancement of growth. PMID- 2332718 TI - Alterations of serum concentrations of thyroid hormones and sex hormone-binding globulin, nuclear binding of tri-iodothyronine and thyroid hormone-stimulated cellular uptake of oxygen and glucose in mononuclear blood cells from patients with non-thyroidal illness. AB - Nuclear tri-iodothyronine (T3) binding and thyroid hormone-stimulated oxygen consumption and glucose uptake were examined in mononuclear blood cells from patients with non-thyroidal illness (NTI) in which serum T3 was significantly (P less than 0.05) depressed (0.62 +/- 0.12 (S.D.) nmol/l) compared with healthy control subjects (1.45 +/- 0.30 nmol/l). Neither serum TSH nor sex hormone binding globulin differed from that of the control group. Nuclear T3 binding capacity was increased (P less than 0.05) in patients with NTI (10.1 +/- 3.0 fmol/100 micrograms DNA) compared with controls (2.5 +/- 0.9 fmol/100 micrograms DNA). Unstimulated glucose uptake was increased in cells from patients with NTI (2.03 +/- 0.49 mmol/l per mg DNA per h, P less than 0.01) compared with controls (1.13 +/- 0.20 mmol/l per mg DNA per h). Thyroxine-stimulated glucose uptake (stimulated glucose uptake--unstimulated glucose uptake) was increased in cells from patients with NTI (2.06 +/- 1.67 mmol/l per mg DNA per h, P less than 0.01) compared with controls (0.26 +/- 0.12 mmol/l per mg DNA per h), and T3-stimulated glucose uptake was also increased in cells from patients with NTI (1.34 +/- 0.81 mmol/l per mg DNA per h, P less than 0.05) compared with controls (0.24 +/- 0.10 mmol/l per mg DNA per h). In contrast, neither unstimulated nor thyroid hormone stimulated oxygen consumption differed. We conclude that both increased nuclear T3 binding and increased thyroid hormone-induced glucose uptake may represent counter-regulatory mechanisms which tend to maintain intracellular homeostasis. PMID- 2332719 TI - Non-sulphated cholecystokinin in human medullary thyroid carcinomas. AB - The expression of gastrin/cholecystokinin (CCK) peptides and their precursors was examined in 16 medullary carcinomas of the human thyroid. Measurements with libraries of sequence-specific radioimmunoassays before and after enzymatic cleavage of extracts and chromatographic fractions showed that the carcinomas contained 1.7 pmol carboxyamidated CCK/g tissue (median; range 0.6-21.8 pmol/g), 0.9 pmol glycine-extended precursor/g (median; range less than 0.2-2.3 pmol/g) and 2.3 pmol further COOH-terminal-extended proCCK/g (median; range 0.9-6.2 pmol/g). Neither carboxyamidated gastrins nor any progastrins could be measured. Gel and reverse-phase chromatography revealed only small molecular forms, i.e. greater than 90% of the amidated immunoreactivity eluted like non-sulphated CCK-8 or CCK-7. The results show that human medullary thyroid carcinomas synthesize CCK peptides. The predominance of non-sulphated CCK is unusual. Taken together with earlier observations from dogs and pigs, our results raise the possibility that small non-sulphated CCK peptides modulate thyroid C-cell secretion in an autocrine manner. PMID- 2332720 TI - Form categorization in 10-month-olds. AB - In five experiments, 10-month-olds were habituated to exemplars of a form category and tested for categorization in paired-comparison trials involving in category versus out-of-category stimuli. Across these experiments, color was systematically manipulated during habituation and/or test trials. Infants categorized form when color was either held constant or varied during habituation, but failed to categorize form when exposed to color-constant stimuli during habituation and tested for categorization with novel-color form exemplars. Two subsequent experiments traced this failure to the narrow experience of exposure to color-constant exemplars during habituation. These results suggest that (a) infants' internal representation for a category will not include a stimulus dimension not varied in the exemplars from which the category was derived, but (b) if variation in that dimension is experienced, exemplars constructed of novel instances of that dimension will still be regarded as belonging to the category. PMID- 2332721 TI - Problems brought about by "reading" a sequence of pictures. AB - The "reading" of a sequence of narrative pictures has been studied as a specific cognitive area. Sequences of pictures were presented to children between 3 and 7 1/2 years old in either the right or wrong order. We studied four problems: the child's difficulty in seeing the same character throughout different representations, the liking-up process of several pictures into one story, the correlation between the temporal order and the spatial disposition of pictures, and the child's tendency to consider the setting of pictures as a puzzle to solve. The characteristic difficulties observed seem to be related to the double status of the picture, which is both a physical and a symbolic object. We set out to reconstruct the path taken from the initial dilemma in which a child finds herself/himself, caught between the signifier and the signified, up until the point where, all contradictions resolved, she/he definitively acquires the principles of the way in which a sequence of pictures functions. Although more or less distinct stages concerning the acquisition of different rules inherent in a sequence of pictures can be observed, the existence of transitional periods favors a continuous progression. PMID- 2332722 TI - Impact of practice on speed of mental rotation. AB - We tested 11- and 20-year-olds on 3360 trials of a mental rotation task in which they judged if stimuli presented in different orientations were letters or mirror images of letters. Children's and adults' processing times decreased substantially over practice. These changes were well characterized by hyperbolic and power functions in which most of the parameters of those functions were constrained to adults' values. Performance on two transfer tasks, mental rotation of letter-like characters and memory search for numbers, indicated that the practiced skill did not generalize to other domains. The results are discussed in terms of different mechanisms that might be responsible for the impact of practice. PMID- 2332723 TI - Children's self-assessment of performance and task-related help seeking. AB - The present research examined the role of self-assessment of performance on children's use of help-seeking as an achievement strategy. In two experiments, third- and fifth-grade children were blocked into low and high verbal skill groups. Children performed a multitrial verbal task in which they were required to indicate their confidence in the correctness of their tentative solution and then were given the opportunity to seek help before providing a final solution on each trial. The second experiment differed from the first in that subjects were provided with a common motivation for seeking help. Subjects' confidence in the correctness of their solution was found to influence both the frequency and type of help sought. High task-related skill was associated with the discriminating use of help-seeking as an achievement strategy, especially among boys. Also, both the frequency and type of help sought varied with self-assessments for older children more than for younger children. Findings are discussed in terms of grade and sex differences in the use of internally based cues for performance evaluation. The importance of accounting for the interplay of children's age and task specific skill with achievement-related goals is stressed. PMID- 2332724 TI - Mental effort and elaboration: effects of accessibility and instruction. AB - The present study examined the effects of accessibility to relevant schematic knowledge for elaboration in the associative learning of noun pairs. Fifth-grade participants performed two simultaneous tasks--associative learning and finger tapping--so that the mental effort demands of elaborating pairs that varied in accessibility could be estimated. The mental effort expended during the creation of sentence elaborations was greater for inaccessible pairs than accessible pairs. This accessibility difference was not observed when subjects were provided with the pair members in sentences. These findings confirm information-processing analyses of the elaboration process and support a knowledge-base interpretation of developmental differences in elaboration effort. PMID- 2332725 TI - Discrimination training of mirror-image stimuli with a delayed-prompt technique: some critical dimensions of extra-stimulus prompts. AB - Research on fading and delay procedures has shown that extra-stimulus prompts frequently fail to help children learn difficult discriminations. The present study analyzed two delay conditions for an extra-stimulus prompt to help preschoolers discriminate mirror-image stimuli as a function of the configurations and locations of the prompts. All subjects were selected on their ability to discriminate the task stimuli in the presence of a third stimulus, a replica of the S+ and an arrow pointing to that stimulus; and on their inability to do so without these stimuli. Experiments 1 and 2 compared these prompt configurations (S+ replica, arrow) when presented equidistant from the task stimuli. Experiment 3 analyzed the contribution of the replica configuration in terms of its location, in between stimuli or immediately above the S+. Experiment 4 investigated the extent to which the results of the previous experiments could be influenced by the methodology for the assessment of prompt control. The results consistently demonstrated that most subjects did not learn the task unless the extra-stimulus prompt had the same configuration as the S+ and was located equidistant from both task stimuli. PMID- 2332726 TI - Infants' perception of timbre: classification of complex tones by spectral structure. AB - Infants 7 to 8.5 months of age were tested for their discrimination of timbre or sound quality differences in the context of variable exemplars. They were familiarized with a set of complex tones with specified spectral structure; members of the set varied in fundamental frequency, intensity, or duration. Infants were then tested for their detection of tones that contrasted in spectral structure but were similar in other respects. They successfully differentiated the two spectral structures in the context of these variations, indicating that they can classify tonal stimuli on the basis of timbre. When the stimuli were organized into arbitrary categories, infants were unable to differentiate these categories, indicating that their performance with nonarbitrary categories was not attributable to memorization of the familiarized set. PMID- 2332727 TI - Size constancy at birth: newborn infants' responses to retinal and real size. AB - Two experiments are described whose aim was to investigate whether perception of size at birth is determined solely by proximal (retinal) stimulation, or whether newborn babies have the ability to perceive an object's real size across changes in distance. In Experiment 1, preferential looking between pairs of stimuli which varied in real size and viewing distance was found to be solely determined by retinal size, suggesting that changes to proximal stimulation can have profound effects on newborns' looking behavior. However, in Experiment 2 newborns were desensitized to changes in distance (and retinal size) during familiarization trials, and subsequently strongly preferred a different sized object to the familiar one, suggesting that the real size had been perceived as constant across the familiarization trials. These results confirm Granrud's (1987) findings that size constancy is present at birth. PMID- 2332728 TI - Phonological priming and orthographic analogies in reading. AB - Recent work has demonstrated that children can use orthographic analogies between the spelling patterns in words to help in decoding new words (e.g., using beak to read peak; Goswami, 1986, 1988). However, one objection has been that these analogy effects may be due to phonological priming. Two experiments examined the phonological priming alternative. In Experiment 1, a single word reading task compared the use of analogies to read words that shared both orthography and phonology (e.g., most-post), that shared orthography only (e.g., most-cost), or that shared phonology only (e.g. most-toast--the phonological priming condition). Limited effects of phonological priming were found. Experiment 2 then presented the same words embedded in prose passages--"real reading." While the orthographic analogy effect remained robust, the small phonological priming effect disappeared. It is argued that phonological priming is an insufficient explanation of the analogy effect at the single word level, and plays no role in the use of analogies in story reading. PMID- 2332729 TI - MHC class II-derived peptides can bind to class II molecules, including self molecules, and prevent antigen presentation. AB - Seven synthetic peptides corresponding to the polymorphic regions of the alpha and beta chains of the I-Ak molecule were examined for their ability to inhibit the presentation of foreign antigens to antigen-specific, I-A-restricted T cell hybridomas. Two of the peptides, representing the sequences found in the first and third polymorphic regions (PMR) of the A alpha k chain (alpha k-1 and alpha k 3) were capable of inhibiting the presentation of three different HEL-derived peptide antigens to their appropriate T cells. In addition, the alpha k-1 peptide inhibited the presentation of the OVA(323-339) immunodominant peptide to the I-Ad restricted T cell hybridomas specific for it. Prepulsing experiments demonstrated that the PMR peptides were interacting with the APC and not with the T cell hybridomas. These observations were confirmed and extended by the demonstration that the alpha k-1 and alpha k-3 peptides blocked the direct binding of HEL(46 61) to purified I-Ak and that the alpha k-1 peptide blocked the binding of OVA(323-339) to I-Ad. The binding competition experiments suggest that the alpha k-1 peptide binds to the I-Ak molecule from which it was derived with a Kd approximately 10(-5) M, while the alpha k-3 peptide binds slightly less well. These combined data, suggesting that class II-derived peptides can bind to MHC class II molecules, including the autologous molecule from which they are derived, have important implications for the molecular basis of alloreactivity and autoreactivity. Further, they suggest a possible mechanism by which selecting elements, involving only MHC molecules, may be generated in the thymus. PMID- 2332730 TI - Infection with Nippostrongylus brasiliensis or injection of anti-IgD antibodies markedly enhances Fc-receptor-mediated interleukin 4 production by non-B, non-T cells. AB - Non-B, non-T cells from spleen and bone marrow of naive mice produce IL-4 upon stimulation by plate-bound IgE or IgG2a in the presence of IL-3. Infection of mice with Nippostrongylus brasiliensis (Nb) or injection of anti-IgD antibodies, treatments known to cause striking polyclonal IgE responses, increase the number of splenic non-B, non-T cells and cause 10-30-fold increase in IL-4 production by a standard number of these cells. In Nb-infected mice, IL-4 producing non-B, non T cells can be found in the lungs, a site through which Nb larvae migrate. Non-B, non-T cells from anti-IgD-injected mice produce IL-4 in response to anti-IgE antibodies, indicating that these cells have been sensitized in vivo with IgE and that crosslinkage of such IgE can lead to stimulation of lymphokine production. Similarly, non-B, non-T cells from Nb-infected mice produce IL-4 upon stimulation with Nb-antigen, indicating that antigen can also crosslink receptors on in vivo sensitized non-B, non-T cells and stimulate lymphokine production. The striking increases in the IL-4-producing capacity of the splenic non-B, non-T cell population in anti-IgD-injected and Nb-infected mice and the in vivo sensitization of these cells strongly suggests that they may have an important role in lymphokine production in helminthic infections and other situations marked by striking elevations of serum IgE levels. PMID- 2332731 TI - Genotype-restricted growth and aging patterns in hematopoietic stem cell populations of allophenic mice. AB - We have studied contributions to hematopoiesis of genetically distinct stem cell populations in allophenic mice. Chimeras were made by aggregating embryos of inbred strains known to differ with respect to stem cell population kinetics. One partner strain (DBA/2) has previously been shown to normally have a stem cell (CFU-S) population of which 24% are in S-phase of the cell cycle, whereas the homologous population of the other partner strain (C57BL/6) was characterized by having only 2.6% in cycle (7). Contributions of the chimeric stem cell population to mature blood cell pools were studied throughout the life of the mice and intrinsic differences in stem cell function and aging were reflected in dynamic patterns of blood cell composition. The DBA/2 stem cell population was eclipsed by stem cells of the C57BL/6 genotype and, after 1.5-3 yr, the hemato-lymphoid composition of 22 of 27 mice studied for this long had shifted by at least 25 percentage points toward the C57BL/6 genotype. 8 of the 27 had hematolymphoid populations solely of C57BL/6 origin. To test whether or not a population of stem cells with an inherently higher cycling rate (DBA/2) might have a competitive advantage during repopulation, we engrafted allophenic marrow into lethally irradiated (C57BL/6 x DBA/2)F1 recipients. DBA/2 hematopoiesis was predominant early, far outstripping its representation in the marrow graft. Perhaps as a consequence of inherently greater DBA/2 stem cell proliferation, the populations of developmentally more restricted precursor populations (CFU-E, BFU-E, CFU-GM, CFU-GEMM) showed an overwhelming DBA/2 bias in the first 2-3 mo after engraftment. However, as in the allophenic mice themselves during the aging process, the C57BL/6 genotypic representation was ascendant over the subsequent months. The shift toward C57BL/6 genotype was first documented in the marrow and spleen precursor cell populations and was subsequently reflected in the circulating, mature blood cells. Bone marrow-derived stromal cell cultures from engrafted mice were studied and genotypic analyses showed donor representation in stromal cell populations that reflected donor hematopoietic contributions in the same recipient. Results from these studies involving two in vivo settings (allophenic mice and engraftment by allophenic marrow) are consistent with the notion that a cell autonomous difference in stem cell proliferation confers on one population a competitive repopulating advantage, but at the expense of longevity. PMID- 2332732 TI - Retinol is essential for growth of activated human B cells. AB - When EBV-transformed human B cells are removed from conventional cell cultures, washed, and seeded at a low cell density in serum-free medium, their growth potential is greatly diminished. Fresh serum restores the growth of low density B cell cultures. We have traced this restorative effect to an essential factor present in the lipid fraction of serum and have identified it as all-trans retinol. The identification is based on the close similarities of the factor isolated from serum with authentic all-trans retinol as revealed by mass spectrometry, HPLC chromatography, and the ability to stimulate the growth of lymphoblastoid cells in the bioassay. Retinol is active at concentrations equal to its concentration in serum. Retinol is also a requirement for growth in suspension cultures at cell densities of 3 x 10(5)/ml. Cells removed at any time from such exponentially growing cultures and transferred to retinol-free medium cease to grow and consequently die, whereas in the continued presence of retinol, cell growth is unabated. All-trans retinal can substitute for retinol, but retinoic acid fails to stimulate the growth of lymphoblastoid cells at physiological concentrations. Normal human B lymphocytes also require retinol as a costimulator of proliferation after activation by anti-mu antibody or Staphylococcus aureus (Cowan strain) bacteria. In serum, retinol is bound to retinol-binding protein, which in turn forms a complex with prealbumin. Accordingly, we find that B cells respond to retinol bound to its physiological serum carrier, retinol-binding protein. In conclusion, human B cells are critically dependent for optimal growth in cell culture on an external supply of retinol. PMID- 2332733 TI - Neurohormones regulate T cell function. AB - In this communication we show that T cell locomotion is affected by direct interaction with neurohormones. Opioid peptides, including beta-END, MET-ENK, LEU ENK, and related enkephalin analogues enhanced migration of human peripheral blood T lymphocytes. Activity was dependent on the peptide NH2-terminal sequence, stimulated by enkephalin analogues with specificity for classical delta or mu types of opiate receptor, and inhibited by the opiate receptor antagonist naloxone. Our studies suggest that such neuropeptides stimulate T cell chemotaxis by interaction with sites analogues to classical opiate receptors. We propose that the endogenous opioids beta-END, MET-ENK, and LEU-ENK are potent immunomodulating signals that regulate the trafficking of immune response cells. PMID- 2332734 TI - Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules. AB - Growth of early B precursor cells was investigated in vitro by using rIL-7 and IL 7-defective stromal cell line PA6 as separate growth signals. B cell development proceeds through three sequential stages different from the growth signal requirement. The cells in the first stage require PA6 alone for the proliferation, and differentiate into the second stage, which requires both PA6 and IL-7 for its growth. When IL-7 is available for the cells in the second stage, they proliferate extensively on the PA6 layer, and some acquire the ability to proliferate in response to IL-7 alone. This sequential change of growth signal requirement, however, does not proceed autonomously along the time schedule. The possibility that it is primarily directed by the result of Ig gene rearrangement is considered. This mode of growth control may explain why only functional B cells are selected in the error-prone process of Ig gene rearrangement during B lineage differentiation. PMID- 2332736 TI - Intracerebroventricular injection of interleukin 1 induces high circulating levels of interleukin 6. AB - IL-1 is known to have a central role in the induction of acute-phase response, and some of its activities (including induction of some acute-phase proteins) were reported to be mediated by an induction of IL-6. Administration to rats of 200 ng of human rIL-1 by intracerebroventricular injection resulted in a more marked induction of circulating IL-6 than the same dose of IL-1 administered systemically (intravenously or intraperitoneally). Induction of serum IL-6 by centrally administered IL-1 was also observed in hypophysectomized or adrenalectomized rats, suggesting that activation of the hypothalamus-pituitary adrenal axis is not essential for this effect of IL-1. IL-6 induction was also observed after pretreatment with indomethacin, indicating that the effect was dissociated from the pyrogenic activity of IL-1. Induction of IL-6 by a central action could represent a novel pathway in IL-1-induced acute-phase response. PMID- 2332735 TI - Negative regulation of human immune deficiency virus replication in monocytes. Distinctions between restricted and latent expression in THP-1 cells. AB - In THP-1 monocytoid cells infected with HIV, viral expression can be regulated in several ways: (a) latency (no viral expression); (b) restricted expression (chronic low-level viral expression with little or no detectable virus released); and (c) continuous production. In cells with restricted HIV expression, nuclear factor(s) were found that blocked tat-associated DNA binding complex formation, suggesting that initiation of transcription was negatively regulated. Also, viral particles were seen budding into and accumulating within intracytoplasmic vacuoles with little virus released, suggesting multiple levels of regulation. These cells with restricted expression had no detectable viral antigens on the cell surface and were not lysed by IL-2-activated large granular lymphocytes. However, they could cause viral-mediated T cell cytolysis in cell-cell assays, suggesting viral transmission through cell contact. In addition, cells with latent HIV were identified and could still produce infectious virus after 5 azacytidine exposure 10 mo later. LPS and other treatments could increase viral production in cells with restricted but not latent expression, suggesting they occur by distinct mechanisms. These infected cells provide a reservoir for viral transmission to uninfected T cells that itself is not detected by immune surveillance mechanisms. PMID- 2332737 TI - Regulation of antigen presentation by acidic pH. AB - The effect of pH on functional association of peptide antigens with APC membranes was investigated by using aldehyde-fixed B cells and class II-restricted T cell hybridomas to assess antigen/MHC complex formation. The results indicated that the rate and extent of functional peptide binding was markedly increased at pH 5.0 as compared with pH 7.3. The pH dependence of binding was preserved after pretreatment of fixed APC with pH 5.0 buffer, suggesting that pH had a direct effect on the interaction of peptide with the APC membrane. Similar results were obtained by using several peptides and I-Ad- and I-Ed-restricted T cells, indicating that pH may be of general importance in regulating the formation of functional antigen/class II MHC complexes. PMID- 2332738 TI - Comparison of the damage-promoting effects of leukotrienes derived from eicosapentaenoic acid and arachidonic acid on the rat stomach. AB - The ability of leukotrienes derived from eicosapentaenoic acid were compared with counterpart leukotrienes derived from arachidonic acid in terms of their ability to affect susceptibility of the stomach to injury induced by a topical irritant and their ability to alter gastric blood flow. Intra-arterial infusion of leukotriene C4 (LTC4) and LTD4 (0.1-3 micrograms/kg/min for 5 min) produced dose dependent increases in gastric mucosal damage induced by topically applied 20% ethanol, as assessed macroscopically, by changes in transmucosal potential difference and by measurement of efflux of protein into the gastric lumen. Similar doses of LTC5 or LTD5 did not produce significant changes in any of these three parameters, when compared with control rats receiving the vehicle. With a higher dose of LTC5 or LTD5 (5 micrograms/kg/min), significant damage was observed. LTC4 and LTD4 were also found to be more potent at reducing gastric blood flow than LTC5 and LTD5. These results demonstrate that the peptido leukotrienes derived from eicosapentaenoic acid (LTC5 and LTD5) are on the order of five times less potent than the leukotrienes derived from arachidonic acid (LTC4 and LTD4), in terms of increasing the susceptibility of the gastric mucosa to damage and reducing gastric blood flow. These results may have important implications in terms of the hypothesis that fish oil diets may be protective or may accelerate healing in ulcerative diseases of the gastrointestinal tract. PMID- 2332739 TI - Remuneration of family physicians. PMID- 2332740 TI - Sampling methods in fatigue study. PMID- 2332741 TI - Family practice as a specialty. PMID- 2332742 TI - Suspected child sexual abuse. PMID- 2332743 TI - Consequences of the National Cholesterol Education Program. PMID- 2332744 TI - Effect of appointment scheduling and reminder postcards on adherence to mammography recommendations. AB - A brief, simple intervention designed to increase the adherence of female patients to their physicians' recommendations for screening mammograms was tested in several midwestern sites. Compared with a control group in which women were examined, told about mammography, and instructed to make an appointment for themselves, an intervention that scheduled appointments for women on the spot and followed up with a reminder postcard increased adherence at every site. Such an intervention, if implemented on a wide scale, would augment the value of screening mammography in controlling breast cancer. PMID- 2332745 TI - Epididymo-orchitis: a retrospective study of 121 patients. AB - One hundred twenty-one patients with acute epididymitis or epididymo-orchitis were evaluated retrospectively according to their clinical symptoms, duration of symptoms, physical examination, and laboratory studies. The patients younger than 30 years of age usually showed less severity of symptoms than the patients older than 50 years of age. The latter often demonstrated evidence of outflow obstruction. Eighty-two percent of patients with demonstrated urographic abnormalities had lower tract abnormalities, mainly secondary to outflow obstruction. All of these patients were older than 50 years of age. An intravenous pyelogram is indicated only in patients over 50 years of age and in young adults with positive bacteriologic urine culture. PMID- 2332746 TI - Maternal birthing positions and perineal injury. AB - A study to evaluate the relationship between maternal birthing position and perineal outcome was undertaken on 335 patients in a rural family physician's practice whose babies were delivered vaginally between December 1980 and December 1988. The most common birthing position used by the women was the semi-sitting position in the birthing bed (44%, n = 146). Ninety-four women (28%) gave birth from the conventional lithotomy position, 80 (24%) used the birthing chair, and less than 5% used a side-lying position. Almost 30% of the women gave birth with intact perineum; the incidence of episiotomy was 44%. The use of a particular position for delivery varied with parity, and multiparous women used the semi sitting position in the birthing bed more frequently than did primiparous women. There was no statistically significant relationship between birthing position and perineal outcome for primiparous women. A statistically significant relationship between delivery position and perineal outcome was found for multiparous women. Multiparous women using the birthing bed were more likely to have less perineal trauma than women giving birth on the delivery table. PMID- 2332747 TI - Patient sex role and preference for a male or female physician. AB - A study was undertaken to test whether a patient's sex role, as measured by the Bem Sex Role Inventory, is associated with preference for a male or female physician. One hundred ninety-three patients completed a physician preference survey and the Bem Sex Role Inventory. Thirty-six percent of patients preferred a physician of a specific sex. For women, sex role was associated with preference for a female physician (chi 2 = 16.14, P less than .01). Women with an androgynous sex role who gave a preference always chose a female physician; three fourths of women with an undifferentiated sex role who gave a preference always chose a female physician. Regardless of sex role, men who gave a preference always chose a male physician. For women, these findings support the hypothesis that sex role is associated with preference for a female physician. PMID- 2332748 TI - Primary care needs of Cambodian refugees. AB - Cambodian refugees who endured the Pol Pot regime experienced a horrendous assault on their physical and mental health. The complaints and diagnoses of 168 Cambodian refugees who presented to a family medicine primary care clinic between 1985 and 1987 were examined. Fourteen of these patients were visited in their homes to obtain in-depth perspectives of their health beliefs and needs. The results support the growing awareness that Cambodian refugees require sensitive and sophisticated approaches to dealing with widespread emotional and physical dysfunction. PMID- 2332749 TI - Organizing outpatient data for care of HIV-infected patients. PMID- 2332750 TI - Estimation of power using simulation techniques. PMID- 2332751 TI - A student health HMO as a partnership model within an academic medical center. AB - The Department of Family Practice, College of Medicine, in partnership with the University of Illinois at Chicago, was responsible for the reorganization of the Student Health Service into a health maintenance organization (HMO), Campus Care. Historically, the two campuses of the University of Illinois at Chicago operated student health as an infirmary model. Reorganization of student health into the Campus Care HMO provided expanded health care services to students, preserved more health care dollars in the university system, and provided a nonincremental increase in the size and responsibility of the Department of Family Practice. One year's experience showed that while the capitation was low compared with standard HMOs, the variable and less frequent use of services by the student population resulted in a fiscally viable operation. Numerous transition difficulties were encountered, including the need for rapid systems conversion within a complex university system, reeducation of students as well as traditional university based practitioners for operation in a managed care system, and the rapid expansion of a small family practice department. The positive experience of the University of Illinois at Chicago supports the notion that family practice is better suited to providing student health care than other primary care disciplines. Three issues are paramount to success: (1) approval, support, and protection by higher level administration from university territorialism, (2) a core family practice faculty with strong leadership and experience in high-volume clinical activity, and (3) a close examination of financial resources in light of expected utilization. PMID- 2332752 TI - A nursing home rotation in a family practice residency. AB - A nursing home rotation can be a complementary component of geriatrics education in a family practice residency curriculum. Using nursing homes in teaching geriatrics has been done for some time but has of late received more emphasis. This increasing emphasis has been brought about by the growing health care needs of an aging population and a concomitant focus on education in geriatrics. If implementation of a nursing home rotation is contemplated, both the positive and negative aspects of such action as it relates to the residents, the nursing home, and the nursing home patients should be explored. The rotation as incorporated into the geriatrics curriculum of the Family Practice Residency, Knoxville Unit, University of Tennessee College of Medicine, involves all second-year and third year residents in the medical care for patients of a 222-bed long-term care facility. From an educational standpoint, overall evaluation of the rotation reflects satisfaction. The experience exemplifies personal and comprehensive continuity of patient care. Other educational benefits include desensitization to the nursing home environment, understanding the kinds of medical care that can be delivered in this setting, and appreciation for the cost not only to the patient and the family but also to the medical care system as well. PMID- 2332753 TI - Commentary on the replacement of neurons in the central nervous system. AB - A theory is proposed by which the replacement of neurons in the central nervous system might take place. The theory is based on our present knowledge of neuroanatomy. PMID- 2332754 TI - Cognitive consequences of congenital deafness. AB - Comparing congenitally deaf children with hearing children on a variety of information processing tasks provides a natural test of the developmental consequences accompanying the long term loss of a particular sensory input. In this experiment, two sequential and two spatial tasks were used to evaluate the way deaf and hearing individuals process these different types of information. When deaf students were asked to recall the order of a string of lights, they performed as well as hearing students. Deaf students were at a significant disadvantage, however, when processing sequentially presented digits. Deaf students performed as well as hearing students on two complex, standardized spatial tasks. The loss of a major sensory modality had minimal effect on three of the four tasks investigated in the present study. Explanations for the single task with a performance differential are considered. PMID- 2332755 TI - Social knowledge and social competence: number and quality of strategies as predictors of peer behavior. AB - The purpose of this study was to examine the ability of two different measures of preschool children's social strategy knowledge to predict classroom behavior with peers. Thirty-two 4- and 5-year-old children attending a university sponsored preschool were administered the Preschool Interpersonal Problem-Solving Tests (PIPS) and an enactive assessment of strategy knowledge. Observational and teacher-rating measures of children's positive and aggressive peer behavior were also obtained. Significant correlations were obtained between (a) the number of strategies produced in the enactive measure and cooperative play ratings by teachers, (b) the number of strategies produced in the PIPS and observations of positive peer behavior, and (c) ratings of friendliness in the PIPS and teacher rated cooperative play and aggression and observations of aggression. Results are discussed in terms of implications for social skill training. PMID- 2332756 TI - Mothers' use of personal pronouns when talking with toddlers. AB - The verbal interaction of 2-year-old children (N = 46; 16 girls, 30 boys) and their mothers was audiotaped, transcribed, and analyzed for the use of personal pronouns, the total number of utterances, the child's mean length of utterance, and the mother's responsiveness to her child's utterances. Mothers' use of the personal pronoun we was significantly related to their children's performance on the Stanford-Binet at age 5 and the Wechsler Intelligence Scale for Children at age 8. Mothers' use of we in social--vocal interchange, indicating a system for establishing a shared relationship with the child, was closely connected with their verbal responsiveness to their children. The total amount of maternal talking, the number of personal pronouns used by mothers, and their verbal responsiveness to their children were not related to mothers' social class or years of education. PMID- 2332757 TI - Development of the concept of family in elementary school children. AB - Two studies were conducted to examine the relation of age, gender, and family structure to children's understanding of the concept of family. In Study 1,387 children in Grades 1 through 6 were asked to classify various groupings of individuals as constituting or not constituting a family. Results showed both age and gender differences in children's conceptions of families: Younger children, especially boys, generally used concrete, absolute criteria for defining a family; younger girls were similar to older children in that they were more likely to employ abstract, relational criteria for family definition. Results also showed that children's own family structure was not related to their family definitions. In Study 2, 64 children from the original sample were given a measure of cognitive ability to examine whether differences in cognitive development or differences in socialization were a likely source of younger girls' more advanced understanding. Gender differences in cognitive ability did not emerge, suggesting that the gender effects in Study 1 reflected differences in the socialization of boys and girls. Implications of the findings for understanding children's reactions to family disruption are discussed. PMID- 2332758 TI - Interactions of preschool and kindergarten friends and acquaintances. AB - The interactions of 4-, 5-, and 6-year-old friends and acquaintances in a peer teaching and game-playing situation were examined. The sample consisted of 102 children who were divided into pairs of same-age, same-sex friends or acquaintances using sociometrics. One child in each pair was randomly chosen to be the teacher and the other the learner. The teachers taught a novel board game to the learners. The most common teaching method was a combination of explaining and demonstrating the rules before the game began; older children gave more comprehensive instructions than younger children. At all ages, teachers were more likely than learners to take the first turn, issue commands, and change the rules. Friends were rated more involved with their partners, more emotionally expressive, and more competitive than acquaintances. Teachers who taught friends were rated more domineering than teachers who taught acquaintances, and learners who were taught by friends were rated more playful and friendly than learners taught by acquaintances. PMID- 2332759 TI - Parent-child conversation of more-liked and less-liked children. AB - Four more-liked boys and four less-liked boys (M age = 58.13 months) were videotaped as they interacted separately in semi-structured activities with their own mother and father, the mother and father of a more-liked boy, and the mother and father of a less-liked boy. Parents of less-liked boys had more intensive interactions that were more controlling, directive, and intrusive than parents of more-liked boys. Parents of more-liked boys had extensive interactive patterns that made them better able to extend praise and encouragement to children not their own. Similarly, more-liked children seemed more sensitive than less-liked children to situational factors that occurred during interactions with parents not their own and were therefore better able to adjust their behavior to the expectations of the situation. PMID- 2332760 TI - The role of older brothers in younger brothers' drug use viewed in the context of parent and peer influences. AB - The purpose of this study was to examine the impact of an older brother's drug use on his younger brother's drug use viewed in the context of parent and peer influences. The sample consisted of 278 White, middle-class male college students and their oldest brothers, who were given questionnaires assessing drug behavior. Results indicated that older brother, parental, and peer drug use each had an independent impact on younger brother's use. The degree of influence varied, with drug modeling by peers and older brothers having a stronger association with younger brother drug use than did parental drug modeling. Further, the older brother's advocacy of drugs was associated with his younger brother's use even if the older brother did not serve as a drug model. Similarly, older brother drug modeling was of importance even if he did not advocate use. Finally, interactive results suggested that older brothers who did not use drugs could offset the negative effects of parental drug risks on younger brother use. Also, younger brothers were least likely to use drugs if both older brothers and peers served as models for nonuse. PMID- 2332761 TI - The infant's concept of agency: the distinction between social and nonsocial objects. AB - The primary purpose of this study was to examine young infants' discrimination between the abilities of social and nonsocial objects to serve as agents. Thirty one infants between 8 months and 8 days old and 14 months and 19 days old were studied. The children's communicative skills were evaluated through frustration episodes in which a toy was taken away in order to elicit communicative behaviors toward the mother. Visual fixation time was compared for events in which an inanimate object moved independently and events in which a human being was the agent. Analysis of the magnitude of decrease of attending responses revealed that the older infants took longer to process anomalous events, whereas the younger infants manifested more interest for events in which an animate being played the role of agent. The findings suggest that infants can distinguish between the causal powers of social and nonsocial objects by the end of the first year. PMID- 2332762 TI - Children's preference for complexity as a function of perceived units in collative motivation. AB - The purpose of this investigation was to manipulate a constant number of four elements (red and blue rectangles) to represent differentially perceived units of complexity. The hypothesis that motivational arousal and choice preferences of second- and fifth-grade children would be a positive function of the number of perceived units, ranging from one to four, was confirmed, consistent with Berlyne's (1960) theory. When the number of elements was held constant at three, as compared to four, similar results were obtained in a test at two intermediate levels of complexity. Implications for organization of elements and the effects of symmetry in determining children's preferences for levels of complexity are discussed. PMID- 2332763 TI - Synthesis and characterization of novel biologically active platinum(II) and palladium(II) complexes of some beta-carboline alkaloids. AB - The preparation of novel biologically active platinum(II) and palladium(II) complexes of some beta-carboline alkaloids (harmaline, harmalol, harmine, and harmane) is described. These complexes, characterized on the basis of their CHN elemental analysis, infrared, Raman and 1H and 13C nuclear resonance spectral data, were shown to have the empirical formula [M(alkaloid)Cl2], M = Pt, Pd. The antitumor and antiviral activities of some of these complexes have been demonstrated. PMID- 2332764 TI - Coordination behavior and antifungicidal, antibacterial, and antifertility activities of dioxomolybdenum(VI) complexes of biologically active heterocyclic benzothiazolines. AB - Synthesis, characterization, and structural aspects of a new class of dioxomolybdenum(VI) complexes with biologically active benzothiazolines, 2-(2 pyridyl) benzothiazoline, 2-(2-thienyl) benzothiazoline, 2-(2-furyl) benzothiazoline, 2-(3-indolyl) benzothiazoline, glyoxal benzothiazoline, biacetylbenzothiazoline, benzil benzothiazoline, and terphthaldehyde benzothiazoline have been described. The newly synthesized complexes, [MoO2(Bzt)2] and [MoO2(Bzt')] (where BztH and Bzt'H2 represent benzothazoline molecules) have been characterized by elemental analysis, conductance measurements, molecular weight determinations, and magnetic studies. Based on IR, 1H NMR, 13C NMR, and electronic spectral studies, distorted octahedral geometry with cis-MoO2 group has been indicated for the resulting complexes. Two benzothiazolines and their corresponding metal complexes were screened for their antifungicidal and antibacterial activity on several fungi and bacteria and found to be quite active in this respect. In addition, antifertility activity of representative ligands and their molybdenum complexes was also evaluated and discussed in male mice. PMID- 2332765 TI - Transition metal complexes of L-cysteine containing di- and tripeptides. AB - Nickel(II), cobalt(II), zinc(II), and cadmium(II) complexes of Ala-Cys, Phe-Cys, and Ala-Ala-Cys were studied by potentiometric and spectroscopic methods. Ni(II) induces deprotonation and coordination of the amide nitrogens, and the stable monomeric or oligomeric complexes are formed, depending on the metal to ligand molar ratios. Formation of the stable bis-complexes with [S,O] coordination mode is characteristic for cobalt(II), zinc(II), and cadmium(II) ions. PMID- 2332766 TI - Nuclear magnetic resonance studies of the solution chemistry of metal complexes. 26. Mixed ligand complexes of cadmium, nitrilotriacetic acid, glutathione, and related ligands. AB - The complexation of glutathione and related ligands by the nitrilotriacetic acid complex of Cd2+ (Cd(NTA)-) has been investigated by 1H NMR as a model for the coordination chemistry of Cd2+ and GSH in biological systems. Related ligands included glycine, glutamic acid, cysteine, N-acetylcysteine, penicillamine, N acetylpenicillamine, mercaptosuccinic acid, and the S-methyl derivative of glutathione. The nature of the complexes formed was deduced from 1H NMR spectra of Cd(NTA)- and the ligands. Mixed ligand complexes (Cd(NTA)L) and single ligand complexes (CdLx) are formed with the thiol ligands, whereas only mixed ligand complexes form with glycine, glutamic acid and S-methylglutathione. Formation constants of the mixed and the single ligand complexes were determined from NMR data. The results indicate that formation constants for binding of a thiolate donor group by Cd2+, either as the free ion or in a coordinately unsaturated complex, are in the range 10(5)-10(6). PMID- 2332767 TI - Reaction of cis- and trans-[PtCl2(NH3)2] with reduced glutathione inside human red blood cells, studied by 1H and 15N-[1H] DEPT NMR. AB - Reactions of cis- and trans-[PtCl2(NH3)2] with glutathione (GSH) inside intact red blood cells have been studied by 1H spin-echo nuclear magnetic resonance (NMR). Upon addition of trans-[PtCl2(NH3)2] to a suspension of red cells, there was a gradual decrease in the intensity of the resonances for free GSH, and new peaks were observed that were assignable to coordinated GSH protons in trans [Pt(SG)Cl(NH3)2], trans-[Pt(SG)2(NH3)2], and possibly the S-bridged complex trans [[NH3)2PtCl)2SG]+. Formation of trans-[Pt(SG)2(NH3)2] inside the cell was confirmed from the 1H NMR spectrum of hemolyzed cells, which were ultrafiltered to remove large protein molecules; the ABM multiplet of the coordinated GSH cys beta CH2 protons was resolved using selective-decoupling experiments. Seventy percent of the total intracellular GSH was retained by the ultrafiltration membrane, suggesting that the mixed complex trans-[Pt(SG)(S-hemoglobin)(NH3)2] also is a major metabolite of trans-[PtCl2(NH3)2] inside red cells. The reaction of cis-[PtCl2(NH3)2] with intracellular GSH was slower; only 35% of the GSH had been complexed after a 4-hr incubation compared to 70% for the trans isomer. There was a gradual decrease in the intensity of the GSH 1H spin-echo NMR resonances, but no new peaks were resolved. This was interpreted as formation of high-molecular weight Pt:GSH and mixed GS-Pt-S(hemoglobin) polymers. By using a 15N-[1H] DEPT pulse sequence, we were able to study the reaction of cis [PtCl2(15NH3)2] with red cells at concentrations as low as 1 mM. 15NH3 ligands were released, and no resonances assignable to Pt-15NH3 species were observed after a 12-hr incubation. PMID- 2332768 TI - Autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma: very low treatment-related mortality in 100 patients in sensitive relapse. AB - One hundred patients with B-cell non-Hodgkin's lymphoma (NHL) in sensitive relapse or incomplete first remission underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MAb)-treated autologous bone marrow transplantation (ABMT). These patients demonstrated good performance status with a Karnofsky score of 80% or greater. The majority of these patients had one or more adverse prognostic features including a failure to achieve a complete remission (CR) with conventional combination chemotherapy (37 patients), bone marrow infiltration (69 patients), a history of extranodal disease other than bone marrow infiltration (42 patients), and histologic conversion (18 patients). At the time of ABMT, only 52 patients were in CR; however, all patients achieved a minimal disease state following conventional intensive therapy. Moreover, at the time of marrow harvest, 37 of these patients had histologic evidence of lymphoma cells infiltrating the marrow. Following high-dose ablative therapy, two acute in-hospital treatment-related deaths were observed. Two late deaths were observed, not due to recurrent lymphoma. Of the remaining 96 patients, 61 are in unmaintained CR with a median follow-up of 13 months. Kaplan-Meier actuarial analysis predicts 50% probability of disease-free survival (DFS) at 37.8 months. This very low treatment-related mortality provides the rationale to apply high dose therapy and ABMT as consolidative therapy for patients in first remission who are at high risk for relapse following conventional therapy. PMID- 2332769 TI - A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: effects of tumor burden and antigen expression. AB - Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. HAMA was detected in five patients. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I. PMID- 2332770 TI - Allogeneic bone marrow transplantation for patients with high-risk acute lymphoblastic leukemia. AB - Seventy-four consecutive patients with high-risk acute lymphoblastic leukemia (ALL) were given cyclophosphamide (CY; 50 mg/kg on each of 4 days) plus total body irradiation (TBI; 300 rad on each of 4 days) followed by a human leukocyte antigen (HLA)-identical allogeneic bone marrow transplant (BMT). Eighteen patients in first complete remission (CR1), 36 in CR2, 16 in CR3, and four in CR4 were transplanted. Patients in CR1 were transplanted 1 to 8 months (median, 3 months) after attaining CR. All 18 patients in CR1 had one or more poor risk factors: age more than 18 (N = 17), initial leukocyte count greater than or equal to 20,000 (N = 11), Ph 1 chromosome (N = 2), delay in attaining CR more than 6 weeks (N = 8), or extramedullary disease (N = 1). Of those transplanted in CR2, 72% had relapsed on therapy. The 5-year event-free survival (EFS) rates for patients transplanted in CR1, CR2, and CR3 are 42%, 43%, and 25%, respectively, at median follow-up times of 57, 54, and 72 months, respectively. Children aged less than 18 years transplanted in CR2 have a 5-year EFS rate of 54%. All CR4 patients died early after transplant. The actuarial probability of relapse is 20%, 26%, and 48% for those transplanted in CR1, CR2, and CR3, respectively. Although there was substantial transplant-associated mortality, it decreased over the decade of the study (P = .01). This study indicates that BMT offers an attractive alternative to postremission chemotherapy in patients in CR1 with poor prognostic factors and in patients in second remission. PMID- 2332771 TI - Immunosuppressive effects of pentostatin. AB - The immune function of patients with hairy cell leukemia (HCL) and solid tumors was evaluated before and after treatment with the investigational drug 2' deoxycoformycin (pentostatin; dCF). Thirteen HCL patients received doses of dCF of 2 to 4 mg/m2 intravenously at 2- to 6-week intervals for up to 15 courses. After completion of treatment, 12 of 13 patients had resolution of severe monocytopenia and five of nine had normal monocyte antibody dependent cellular cytotoxicity. There was statistically significant depression of total lymphocytes, T cells, and B cells. Evaluation of T subsets showed a decrease in CD4+ cells. Immunoglobulin G (IgG) in sera were decreased from baseline, while IgM and IgA were unaffected. There was no significant effect on skin-test reactivity or large granular lymphocyte numbers. Lymphoblastic transformation was variably affected. Natural-killer (NK) cell function was improved or unchanged after dCF treatment. Reevaluation of seven patients at 21 to 119 weeks after receiving dCF demonstrated that recovery to normal T- and B-cell numbers and subsets does occur. Five solid tumor patients were given dCF at 4 mg/m2 intravenously at 1- to 2-week intervals for up to five courses. There was significant reduction in T cells, B cells, CD4+, and CD8+ cells with no statistically significant effect on the other immune parameters. We conclude that low doses of dCF can cause persistent immunosuppression though recovery may occur after the drug is stopped. In patients followed after completion of dCF, there was no associated increase in second malignancies or unusual infections. PMID- 2332772 TI - Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma. AB - Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma. PMID- 2332773 TI - Failure of 1H nuclear magnetic resonance spectroscopy of blood plasma to detect malignancy. AB - Water-suppressed proton nuclear magnetic resonance (NMR) of plasma was proposed as a technique for detecting malignant tumors. In that analysis, bloods drawn from cancer patients at the Beth Israel Hospital (BIH; Boston, MA), were easily distinguished from normal subjects by measuring and averaging the proton NMR methyl and methylene line widths of plasma lipoproteins. We collected blood at the Massachusetts General Hospital (MGH), including from normal controls, patients with untreated and treated malignant tumors, and patients with nontumor diseases. The plasma NMR analyses were carried out blind. The code was not broken until all patient charts and pathology records were reviewed, plasma analyses were completed, and patients had been divided into appropriate clinical groups. Analysis of these data showed no differences between the means of the study groups (false-positive and false-negative frequencies 46% and 57%, respectively). An inverse correlation of methyl/methylene line widths with age (P less than .01), and a correlation with nitrate-requiring cardiovascular disease (P less than .05) was, however, evident. This test cannot be validly used to detect malignancy. PMID- 2332774 TI - Intensive therapy in elderly patients with acute myeloid leukemia. PMID- 2332775 TI - Toxicity of etoposide, doxorubicin, and cisplatin in gastric cancer. PMID- 2332776 TI - EAP in advanced gastric cancer. PMID- 2332777 TI - To lap or not to lap. PMID- 2332778 TI - Contrast medium "recalls" interleukin-2 toxicity. PMID- 2332779 TI - Kinetics of antimicrobial activity of amoxicillin/clavulanic acid and metronidazole against beta-lactamase-producing Bacteroides fragilis group. AB - Bacteroides fragilis group are the most common anaerobic bacteria isolated in clinical specimens. The use of a beta-lactam with a beta-lactamase inhibitor should result in a marked increase in the group's sensitivity to the beta lactams. Since the activity (MIC) shown by the amoxicillin + clavulanic acid combination against Bacteroides fragilis group is good, other parameters of in vitro activity have been studied. This study was also done with metronidazole. The minimum inhibitory concentration (MIC) was determined in 26 strains of Bacteroides fragilis group (14 B. fragilis; 5 B. thetaiotaomicron; 4 B. vulgatus; 3 B. distasonis). Likewise, the minimum bactericidal concentration (MBC), the killing curve, the sub-MIC and post-antibiotic effect were determined. The MIC ranged between 0.5 and 32 mg/l. The MBC was two- to four-fold the MIC for amoxicillin/clavulanic acid, and one- to two-fold the MIC for metronidazole for most strains. The killing curve showed a continuous decrease, sloping most sharply between 0-2 hours and 6-8 hours. Amoxicillin + clavulanic acid showed a post-antibiotic effect between 2 and 4 hours. The inhibitory minimum antibiotic concentration was one-half the MIC for most strains. PMID- 2332780 TI - The effect of subinhibitory concentrations of some antibiotics on the hydrophobicity of gram-negative bacteria. AB - Cell surface hydrophobicity is currently regarded as an important factor in promoting bacterial adherence to a wide variety of surfaces. This feature was investigated in some Gram-negative bacteria isolated from urinary tract infections and the extent to which their surface characteristics were affected by subinhibitory concentrations of some antibiotics was assayed. Surface properties were evaluated using the salting-out technique (SAT) and bacterial absorption to n-hexadecane (BATH). SAT showed that all except 3 Escherichia coli strains were autoaggregating. BATH detected more hydrophobic characteristics in the stationary phase of bacterial growth. Pretreatment with antibiotics generally reduced hydrophobicity and thus affected the initial reversible phase of attachment of bacteria to eukaryotic cells. PMID- 2332781 TI - Comparative study of the in vitro antibacterial activity of ciprofloxacin and thirteen other antimicrobial drugs with respect to recently isolated pathogens. AB - The in vitro antibacterial activity of ciprofloxacin and 13 other antimicrobial drugs was evaluated with respect to 569 pathogens, mainly isolated from urine. Ciprofloxacin was found active in 96.1% of all of the Gram-positive and Gram negative strains tested, amikacin in 90.6%, ceftazidime in 89.8%, ceftriaxone in 85.3%, piperacillin in 82.7%, tobramycin in 82.6%, gentamicin in 81.5%, aztreonam in 78.3%, nitrofurantoin in 72.6%, cotrimoxazole in 71.6%, cinoxacin in 71.0%, pipemidic acid in 70.6%, nalidixic acid in 66.7%, ampicillin in 50.1%. Ciprofloxacin was found to be the most active of the drugs studied against the bacterial strains which cause urinary, respiratory and other infections. PMID- 2332782 TI - Epidemiology of antibiotic resistance in human isolates of Enterobacteriaceae in Sicily. AB - The authors have studied the antimicrobial susceptibility of 1073 clinical isolates of various genera of Enterobacteriaceae (collected during the period July-December 1988) to ampicillin, piperacillin, cefotaxime, ceftazidime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, norfloxacin, and ciprofloxacin. Antimicrobial susceptibility was determined by Bauer-Kirby disk diffusion method. Of 1073 tested bacteria, 704 (65.6%) produced beta lactamase detectable by nitrocefin test. The highest percentage of resistant strains occurred with ampicillin (70%) followed by piperacillin (24%) and cefotaxime (19%). Lower percentages of resistant strains were found for gentamicin (10%), aztreonam (8%), netilmicin (7%), norfloxacin (5%) and amikacin (4%). Two percent of the strains were resistant to ciprofloxacin and 0.5% to imipenem. The incidence of resistance in Klebsiella sp., Enterobacter sp., E. coli and Proteus sp. was compared to that found among 872 strains isolated during July-Dec. 1984. In all the Enterobacteriaceae, mainly Enterobacter sp., the increase in the resistance was high for ampicillin, piperacillin and cefotaxime and lower for gentamicin. PMID- 2332783 TI - Microbiological patterns of four new imidazole derivatives. AB - The authors present an in vitro experimental study concerning the microbiological properties of four imidazole derivatives, with a piperazine group between two benzene rings. Seventy strains of Gram-positive and Gram-negative bacteria, 30 of yeasts, 14 of filamentous fungi and 10 strains of Trichomonas vaginalis were tested. The new compounds revealed a good inhibitory activity against Gram positive bacteria, yeasts and dermatophytes. These results compare well with those obtained with the other known imidazoles. Moreover any mutagenic activity is absent. PMID- 2332784 TI - The discovery and profile of fluconazole. AB - Fluconazole is a bis-triazolyl, difluorophenyl propyl alcohol derivative being developed for treatment of life-threatening and superficial fungal infections. The presence of a triazole and a difluorophenyl produces potent antifungal activity but replacement of the usual imidazole group by triazole leads to improved selectivity. Fluconazole is much less lipophilic than other azole antifungals and this leads to excellent penetration throughout the body, low protein-binding and water-solubility. Fluconazole is stable to metabolism resulting in excellent oral absorption and a long half-life. These properties have resulted in excellent efficacy and safety in a wide range of clinical situations. PMID- 2332785 TI - Cisplatinum plus epirubicin alternated with cyclophosphamide plus 5-fluorouracil in ovarian cancer. AB - Fifty-two patients with ovarian cancer (post surgical residual tumor) were treated with the combination of platinum + epirubicin (PE) (P 50mg/m2, E 60 mg/m2) alternated with cyclophosphamide + 5-fluorouracil (CF) (C 800 mg/m2, F 600 mg/m2). The treatment was repeated every 28 days for a maximum of 10 cycles. Forty-three patients were evaluable for response. Complete remission (CR) was achieved in 13 (30%) patients (evaluated by second-look), while partial remission (PR) was achieved in 6 (14%) patients for a mean duration of 27 and 14 months, respectively. Eleven out of 13 patients with CR and 5 out of the nonevaluable patients are alive and do not show signs of disease after a mean follow-up of 29 + months (range 19-36). The main factors that conditioned complete remission were the tumor residue and performance status of the patient. PMID- 2332786 TI - In-vitro evaluation of a new oral cephalosporin, cefroxadine (CGP 9000). AB - The in vitro activity of cefroxadine was studied and found to be at least comparable to that previously reported for cefalexin and cefradine. The activity of cefroxadine was superior to that of amoxicillin against tested isolates. Time killing studies showed that the addition of 4 X minimum inhibitory concentration (MIC) of cefroxadine to growing cultures reduced viable counts by 4 log units within a 3 h incubation. A diffusion test with a 30 microgram cefroxadine disk produced acceptable interpretive results with tentative zone size breakpoints of less than or equal to 14 mm for resistance and greater than or equal to 17 mm for susceptibility. PMID- 2332787 TI - Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex. I. Establishment of cell classes. AB - The purpose of this study was to determine whether different classes of neocortical pyramidal neurons possess distinctive electrophysiological properties. Neurons were assigned to classes on the basis of their somadendritic morphology as revealed by intracellular HRP injection. The electrophysiological features of each class are compared in the following paper (Mason and Larkman, 1990). Coronal slices were prepared from the visual cortex of the albino rat and maintained in vitro. Pyramidal neurons from layers 2/3 and 5 were impaled with electrodes containing HRP. After intracellular recording, the cells were injected, reacted to visualize the enzyme, and examined in the light microscope. The 18 neurons from layer 2/3 showed an underlying similarity of somadendritic morphology and were considered to constitute a single cell class, although some features varied with the depth of the soma in the cortex. The 22 layer 5 cells were more diverse and were divided into 2 main classes. Eleven cells had single, thick apical trunks which ascended to close to the layer 1 border then branched to form a terminal arbor. These cells were termed thick layer 5 cells, and were found mainly in the upper part of the layer. Ten layer 5 cells had single apical trunks which tapered to a fine diameter and terminated, without forming an obvious terminal arbor, near the top of layer 4 (3 cells) or in layer 2/3 (7 cells). These cells were termed slender layer 5 cells and were found throughout the layer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332788 TI - Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex. II. Electrophysiology. AB - The aim of this study was to determine whether the different morphological classes of pyramidal neurons in layers 2/3 and 5 of rat visual cortex (Larkman and Mason, 1990) have particular electrophysiological properties. Neurons in in vitro slices of rat visual cortex were impaled with glass micropipettes containing horseradish peroxidase (HRP) and studied using current-clamp techniques prior to pressure injection of HRP into the neurons. On morphological grounds, cells stained in layer 2/3 were placed into a single class whereas layer 5 cells were divided into 2 classes. Cells in one of these classes had thick apical dendrites which arborized in layer 1, whereas the apical dendrites of cells in the other class were thinner and did not reach layer 1 (Larkman and Mason, 1990). Despite variation between individual cells of a single class, significant differences were found in the time constants, current/voltage relations, and repetitive firing behaviors of the 3 classes. Burst firing responses to injected current pulses were confined to the layer 5 cells with thick apical dendrites. These results add to those from other areas of the brain demonstrating that the electrophysiological properties of pyramidal neurons are heterogeneous. Furthermore, we have shown that distinctive intrinsic membrane properties of pyramidal neurons in visual cortex are correlated with different morphologies. PMID- 2332789 TI - Age-dependent differences in reorganization of primary somatosensory cortex following low thoracic (T12) spinal cord transection in cats. AB - The organization of primary somatosensory cortex was examined in chronic spinal cats that had sustained cord transection at T12 at 3 ages: 2 and 6 weeks of age, and as adults. Five months to 1 yr following transection, the deprived cortex was mapped electrophysiologically (multiunit recordings). The topographical organization found at each age was compared to that present in normal adults to study effects of developmental age on the ability of the somatosensory system to adjust to changes in afferent input. Cortical responses to deprivation of somatosensory input were age dependent. In animals cord transected at 2 weeks of age, the remaining somatic afferent input excited both its normal cortical area and the area normally reserved for the hindlimb. This resulted in 2 somatotopic maps of the rostral trunk and forelimb. In contrast, in cats spinalized at 6 weeks of age, there was only 1 map for the remaining somatosensory input that was distributed across the mediolateral axis of the primary somatosensory cortex. As a result, the remaining somatosensory input was shifted medially from its normal position and was narrower with respect to the rostrocaudal area driven by light tactile input. The amount of cortex that each body region could excite was essentially the same as in normal animals. In adults, a third response was observed; regions normally devoted to forelimb and trunk appeared to be unchanged, and the region previously serving the hindlimb responded only to a limited extent, and only to tactile stimulation of the trunk. In all cases, however, some sites in the cortex could be excited by parts of the body that in normal animals were served by cortical regions from 3 to 10 mm away, a distance much in excess of the maximum extent of reported thalamocortical overlap. We suggest that the various patterns of cortical organization observed at different ages reflect different developmental processes that are active at the time of transection. Further, we hypothesize that often, in major denervations such as spinal cord transection, a significant component of the reorganization occurs at synaptic levels below the cortex in young animals. PMID- 2332790 TI - Regulation by exercise of the pool of G4 acetylcholinesterase characterizing fast muscles: opposite effect of running training in antagonist muscles. AB - Fast muscles of rodents characteristically differ from their slow-twitch counterparts by exhibiting high levels of G4, i.e., the tetrameric acetylcholinesterase (AChE) molecular form. Converging evidence suggests that this additional G4 pool is specifically regulated by the type of activity actually performed by the muscle. This hypothesis was tested by studying the effect of a chronic increase in neuromuscular activity on the AChE content and distribution of molecular forms of functionally antagonist rat hindlimb muscles. They included the fast ankle extensors gastrocnemius (GAST) and plantaris (PL), the fast ankle flexors tibialis anterior (TA) and extensor digitorum longus (EDL), as well as the slow-twitch soleus (SOL). Neuromuscular activity was enhanced by subjecting the rats to a 12-week training program consisting of repeated sessions of prolonged endurance running on a rodent treadmill. This exercise regimen preferentially affected the G4 pool characterizing fast muscles which exhibited marked and opposite changes according to the functional role of the muscles. The amount of G4 was increased by more than 50% in the ankle extensors GAST and PL, which play a dynamic role, and reduced by about 40% in the ankle flexors TA and EDL, which exhibit a predominant tonic activity during running. The asymmetric forms A12 and A8 were slightly elevated in the fast muscles. In the case of the slow-twitch SOL, running training resulted in a small, nonspecific decrease in AChE content which affected most of the molecular forms. These data indicate that the size of the G4 pool characteristic of fast muscles depends on the type, dynamic or tonic, of activity actually performed. The present results support the conclusion that this G4 pool fulfills a specific and essential function, distinct from that of A12. PMID- 2332791 TI - Learning and behavioral-long-term potentiation: importance of controlling for motor activity. AB - A series of brief, high-frequency trains of electrical stimulation delivered to the perforant-path results in long-term potentiation (LTP) of the dentate gyrus as measured by average evoked potentials (EPs). Similar increases in dentate evoked potentials have been reported after natural learning. Previous studies of this behavioral LTP have not adequately controlled for ongoing behavior at the time of recording, even though motor activity also influences the amplitude of EPs. Chronically implanted rats were trained in both a radial-arm maze and an avoidance task using a crossover design. EPs in the dentate gyrus following perforant-path stimulation were recorded daily under 3 different behavioral conditions: immobility, movement, and freely behaving. After completion of both tasks, animals were given tetanizing stimulation of the perforant path. Results indicated strong improvements in the performance of both tasks. Tetanization induced significant LTP, which was still present at the end of 5 d. Significant differences were found between EPs collected during immobility and movement throughout the experiment. No evidence of behavioral LTP was observed, and the EPs remained consistent with baseline measures. These data show the necessity of controlling for ongoing behavior at the time of recording in electrophysiological studies of learning. The data also indicate that the phenomenon of behavioral LTP, as assessed by hippocampal EPs, is not universal to all learning experiences. PMID- 2332792 TI - Purine analogs inhibit nerve growth factor-promoted neurite outgrowth by sympathetic and sensory neurons. AB - Past studies have shown that purine analogs block certain, but not all, responses of cultured rat PC12 pheochromocytoma cells to nerve growth factor (NGF). In the present work, newborn rat sympathetic and sensory neurons were exposed to NGF in the presence or absence of the purine analogs 6-thioguanine and 2-aminopurine. These compounds reversibly suppressed NGF-dependent neurite outgrowth by the neurons and did so at concentrations comparable to those effective on PC12 cells. In contrast to their effects on neurites, neither compound significantly blocked NGF-promoted neuronal survival. Similar effects were seen with cultures of chick embryo sympathetic ganglia. These findings show that purine analog effects on NGF responses can be extended to mammalian and avian neurons. Moreover, the differential effects of the analogs on neurite outgrowth and survival indicate that these 2 actions of NGF can be dissected from one another and may represent different mechanistic pathways. PMID- 2332793 TI - Neuromodulation of the crab pyloric central pattern generator by serotonergic/cholinergic proprioceptive afferents. AB - In the stomatogastric nervous system of the crab, Cancer borealis, a set of 4 serotonergic/cholinergic proprioceptive neurons, called gastropyloric receptor (GPR) cells, have effects on the pyloric motor pattern. In a semi-intact foregut preparation, the GPR cells are not activated by movements of the pyloric filter; instead they respond to the slower movements of the gastric mill (Katz et al., 1989). Thus, their activity is not synchronized to the pyloric motor pattern. However, when the GPR cells are stimulated in an in vitro preparation in a manner that resembles their normal firing pattern, they produce dramatic effects on the pyloric motor pattern. These effects include: (1) a prolonged increase in the pyloric cycle frequency, (2) a momentary pause in the motor pattern, (3) transient inhibition of some motor neurons, (4) strong excitation of other motor neurons, and (5) altered phase relationships of the different components of the motor pattern. These changes in the motor pattern are due to direct effects of the GPR cells on neurons in the pyloric central pattern generator (CPG). All of the cells in the pyloric circuit appear to receive GPR input. However, only 2 neurons receive detectable rapid nicotinic synaptic potentials. The other neurons receive only slower neuromodulatory input from GPR stimulation. The neuromodulatory effects include burst enhancement, plateau potential enhancement, excitation, and inhibition. These modulatory effects are largely mimicked by bath applied serotonin (5-HT). Thus, primary sensory neurons can alter the production of motor patterns by a CPG through a phase-independent mechanism; these proprioceptors do not need to fire at a precise time in the cycle to be effective because their effects are mediated through the slower actions of the neuromodulator 5-HT. PMID- 2332794 TI - Steroid hormone regulation of ribosomal RNA in rat hypothalamus: early detection using in situ hybridization and precursor-product ribosomal DNA probes. AB - In the female rat, behavioral and endocrine aspects of reproduction are controlled, in part, by the action of the steroid hormone estradiol on several regions of the brain, including the ventrolateral portion of the ventromedial hypothalamus (VL-VMN) and the arcuate nucleus of the hypothalamus (ARC). Quantitative assessment of the effects of estradiol on the regulation of ribosomal RNA in rat hypothalamus was accomplished in this study by tandem in situ hybridization experiments with 2 ribosomal DNA probes specific to the initial transcript (precursor) or mature, stable (product) rRNA. This novel approach allowed the regulation of RNA processing by steroid hormones to be analyzed in the individual neuron, a particularly important concern in heterogeneous tissue such as the brain. Estradiol was administered subcutaneously to ovariectomized rats for 15 min, 30 min, or 2 hr, or a discontinuous schedule of 2 hr on/7 hr off/2 hr on. Levels of precursor and product rRNA were measured in VL-VMN and ARC neurons using a computerized image-analysis system. Significant increases in the levels of precursor rRNA were observed only in the VL-VMN as early as 30 min after hormone exposure, with a doubling in the amount of precursor rRNA occurring at 2 hr. No changes in product rRNA were observed in either brain region at these early times. These data, in conjunction with our previous findings of increases in product rRNA after longer hormone exposure times, lead us to conclude that rRNA gene transcription is activated in rat hypothalamic neurons within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332795 TI - Age differences in morphology of reinnervation of partially denervated mouse muscle. AB - The effect of age on the ability of motor neurons to develop and maintain an enlarged total axonal and synaptic volume was compared in soleus muscles of 5-8 month and 25-30-month mice, 30-120 d after partial denervation. Before and after partial denervation (transection of the L5 root), the total number of muscle fibers was the same in all muscles. However, in young animals, there was only some transient atrophy and hypertrophy mostly receded by 120 d, whereas in old muscle, a more prominent early atrophy was followed by persistent hypertrophy. Ectopic endplates were not found. In zinc-iodide-osmium (ZIO) stained preparations, muscle fibers with small nerve terminals were present at 60 d and were still present in old muscle at 120 d. Fluorescent staining of nerve terminals and acetylcholine receptors revealed that in young muscle, postsynaptic sites were nearly or completely reoccupied by 60 d. In old muscle, about 22% of former junctions were denervated, with the remainder minimally to fully reinnervated. At 60 d and thereafter, collateral sprouts originated from nodes of Ranvier in both young and old muscle and were remyelinated in young but mainly unmyelinated and remarkably tortuous in old animals. These results, confirmed with immunofluorescent strains for myelin basic protein and neurofilaments, account for many of the physiological findings (Jacob and Robbins, 1990). Motor unit size expanded 2.5 times in young and 2 times in old muscle at 60 d after partial denervation. However, the increment in total quantal output and nerve terminal volume per motor neuron was 60-100% greater than control in young but only 20-25% greater in old muscle, with little further recovery. This inability of the motor neuron in old mice to expand the field of innervation may reflect a limitation imposed by reduced axonal transport. The present findings may elucidate the muscle weakness in postpolio syndrome and amyotrophic lateral sclerosis. PMID- 2332796 TI - Brain pathways for learned and unlearned vocalizations differ in zebra finches. AB - Male zebra finches sing, females do not. However, both sexes produce the "long call" when placed in visual isolation. This call is sexually dimorphic; it includes learned components in males but not in females. The 3 learned features of the male long call are a high fundamental frequency, a fast frequency modulation, and a short, stable duration. These features are learned by the male during development, as is song. Since similar features are also found in song syllables, we wanted to know whether long-call production depends on the same CNS pathway that controls song production. Three critical components of the song pathway are telencephalic nuclei HVC, RA, and the tracheosyringeal (ts) nerves innervating the syrinx. In male zebra finches, bilateral section of the ts nerves affected the fundamental frequency and fast frequency modulations of both the long call and song but left the temporal features intact. Ts nerve section had no effect on the female long call. Bilateral lesions of either HVC or RA in males affected the fundamental frequency, fast frequency modulations, and temporal structure of both the long call and song. Similar lesions had no effect on the female long call. These results demonstrate that HVC, RA, and the ts nerves make critical contributions to the acoustic features of the male long call and song, while the temporal pattern depends on HVC and RA but not the ts nerves. HVC and RA lesions remove all the learned features that distinguish the male call and reveal a simple unlearned vocalization shared by both sexes. We suggest that the learned features of oscine songbird vocalizations are controlled by a telencephalic pathway that acts in concert with other pathways responsible for simpler, unlearned vocalizations. PMID- 2332797 TI - Resting discharge and response dynamics of horizontal semicircular canal afferents of the toadfish, Opsanus tau. AB - The response dynamics of 66 primary afferents of the horizontal semicircular canal were studied in the toadfish using sinusoidal, rotational stimuli from 0.001-10 Hz at amplitudes of 5-100 degrees/sec. Twelve afferents were also tested to constant velocity trapezoids. Responses to sinusoids were used to classify afferents into 3 broad groups: (1) low-gain afferents that maintain a relatively linear response re: stimulus velocity across most of the frequency and amplitude spectra tested; (2) high-gain afferents that have a velocity sensitivity but also show a high-frequency gain enhancement and phase advance; and (3) so-called acceleration afferents that have a response more in phase with stimulus acceleration than velocity across the tested bandwidth. The afferent's background discharge was examined in relation to its rotational response. Low-gain afferents have regular spacing of interspike intervals. High-gain and acceleration afferents have a widely variable discharge regularity that is apparently unrelated to their rotational responses. Input/output transfer models were fit to the response data to describe the low- and high-pass filtering properties of the 3 afferent groups. PMID- 2332798 TI - Efferent vestibular system in the toadfish: action upon horizontal semicircular canal afferents. AB - The influence of the efferent vestibular system (EVS) upon the background discharge and response dynamics of horizontal semicircular canal afferents was examined in the toadfish. In one set of experiments the EVS was activated using a behavioral paradigm; in the second, electrical shocks were applied to the efferent vestibular nucleus in the brain stem. The afferent's background discharge and responses to rotation were recorded before and during efferent stimulation. Both EVS activation paradigms gave qualitatively similar results: a facilitation of the afferent's rate, while the animal was at rest or in motion, and a reduction in response sensitivity. Afferents were not affected uniformly: low-gain, velocity-sensitive afferents were weakly influenced, while high-gain and acceleration afferents having low rates were the most excited. The afferents' phase of response was unmodified by electrical EVS stimulation. In many afferents a prominent form of response nonlinearity is discharge silencing over large portions of the stimulus cycle. Efferent-evoked rate increase was often sufficient to produce a full-cycle bidirectional response. Caloric facilitation of afferent rate confirmed that the EVS-induced sensitivity decrease was rate independent. These results show a dual action of the efferent system: (1) facilitating the afferent's rate and (2) reducing its sensitivity to adequate stimulation that may be correlated with the dual EVS synaptic innervation of the labyrinth, namely postsynaptic efferent-afferent synapses and presynaptic efferent-hair cell synapses. PMID- 2332799 TI - Carboxypeptidase E (CPE): immunocytochemical localization in the rat central nervous system and pituitary gland. AB - Carboxypeptidase E (CPE, enkephalin convertase, carboxypeptidase H; EC 3.4.17.10) is a carboxypeptidase B-like enzyme proposed to be involved in the synthesis of a variety of peptide hormones and neurotransmitters. In the present study we have localized CPE in the rat central nervous system using specific polyclonal antisera to the purified enzyme. Immunoreactive CPE occurs in a variety of cell somas and neuronal terminals in the central nervous system. The enzyme is most concentrated in the hypothalamus, especially in the median eminence, supraoptic nucleus, paraventricular nucleus, and suprachiasmatic nucleus. CPE is also found in axon terminals in the posterior pituitary gland, melanotropes of the intermediate pituitary gland, and select cells of the anterior pituitary gland. Immunoreactivity to CPE in the hippocampus is found in the pyramidal cells and in the inner part of the molecular layer of the dentate gyrus. CPE is also found in the central nucleus of the amygdala and the bed nucleus of the stria terminalis. These results suggest that CPE distribution corresponds to that of many neuropeptides at the fine structural level, thus further implicating CPE in peptide processing. PMID- 2332800 TI - Reticular astrocytes in the fish optic nerve: macroglia with epithelial characteristics form an axially repeated lacework pattern, to which nodes of Ranvier are apposed. AB - Astroglia in lower vertebrate optic nerves are unusual: as shown recently (Giordano et al., 1989; Rungger-Brandle et al., 1989), they express abundant Type II cytokeratin, not glial fibrillary acidic protein (GFAP), the cytoskeletal marker for astrocytes elsewhere. To determine the implications for the glial cells of these epithelial-type cytoskeletons, which are linked up by desmosomal junctions, we analyzed the tissue patterning of fish optic nerve astroglia, which we term reticular astrocytes on account of their uniquely specialized arrangement. The processes of the reticular astrocytes fasciculate extensively with one another in a pattern stabilized by the desmosomes, forming a network laid out in thin planar sheets, or partitions. These are arranged transversely, that is at right angles to the optic fibers and are repeated at regular intervals of about 15 microns longitudinally throughout the optic nerve. They merge periodically forming a 3-dimensional framework whose pattern we speculate provides a flexible tissue skeleton for the optic nerve, capable of accommodating eye movements. Virtually all fibers in mature regions of the optic nerve are myelinated, and we show that nodes of Ranvier mostly occur in register with the partitions, displaying perinodal astrocytic associations resembling those found at CNS nodes in mammals. This clustering may account for the unexpectedly high observed incidence of neighbor pairs of nodes. Among other peculiarities associated with the reticular astrocytic network, one is that up to 20% of all cells comprise foamy macrophages not found elsewhere in the CNS. PMID- 2332801 TI - Potassium channel regulation in Schwann cells during early developmental myelinogenesis. AB - The presence of neuronal-like, voltage-gated ion channels on glia has raised questions concerning their physiological roles. Insights into glial channel function can be gained by examining regulation of channel expression during axoglial interactions. We examine the regulation of Schwann cell potassium channels in developing sciatic nerves of newborn rats when myelin is first laid down. During the initial postnatal week, cell-attached patch-clamp recordings at soma of Schwann cells with visible myelin revealed an inward rectifying potassium channel (KIR), to date described only in CNS glia but not Schwann cells, as well as an outward potassium channel (KO). Around the resting potential, the KO channel is virtually closed, while the KIR channel appears maximally open. Compared with the KO channel, the KIR channel is blocked by low concentrations of Cs+ and exhibits higher sensitivity to 4-aminopyridine (4AP). Further, the KIR channel appears similar to other mammalian inward rectifiers and rectification depends, in part, on cytoplasmic Mg2+. Channel regulation bears an interesting relation to early myelination: as the average number of myelin lamellae increases from 6 to 21 from day 2 to day 8, currents decrease by 80-90%. The reduction in KO current also parallels the known decrease in proliferation of Schwann cells as they are being committed to myelination, supporting the recently proposed notion of a functional link between potassium channels and proliferation. The KIR channels, by virtue of being open at the resting potential, may play a role in buffering activity-dependent K+ accumulation during early myelin formation. The subsequent reduction in somal channel density may parallel a diminished need for K+ buffering as electrogenesis is restricted to nodal regions. PMID- 2332802 TI - The dependence of motoneurons on their target muscle during postnatal development of the mouse. AB - Motoneurons seem to require contact with their target muscle even after embryogenesis is complete, but the consequences of target-deprivation during postnatal development are poorly understood. To examine the fate of motoneurons separated from their targets postnatally, we labeled the motoneurons that innervate the biceps brachii muscle with the retrograde tracer Fluorogold and then separated them from their muscle by amputating the forelimb. Fluorogold was subsequently found within motoneurons, as well as within much smaller cells that were identified as microglia. The number of labeled microglial cells steadily increased with time following limb amputation, while the number of labeled motoneurons declined. The magnitude of this response depended on the age of the animal: the younger the animal at the time of the amputation, the greater the number of labeled microglia and the more extensive the neuronal loss. To ensure that the response to amputation was caused by target deprivation, rather than by the injury itself, the nerve to the biceps muscle was cut or crushed. In this way, axons were transected but target access was only temporarily denied. After the nerve was cut, motoneurons began to reinnervate the muscle within 3 weeks but, just as after amputation, the spinal cord subsequently contained labeled microglia and a reduced number of motoneurons. In contrast, after nerve crush, reinnervation began within 4 d and there was no evidence of motoneuron death. Our results demonstrate that target-deprivation causes motoneurons to be lost in an age- and time-dependent manner, and indicate a critical period after axotomy during which motoneurons must reinnervate their target in order to survive. Further, we provide evidence that microglial cells may phagocytose dying motoneurons. The approach we used would provide a convenient assay for testing candidate motoneuron growth factors in animals where in vivo studies of the embryo are difficult. PMID- 2332803 TI - Localization of the MARCKS (87 kDa) protein, a major specific substrate for protein kinase C, in rat brain. AB - The localization of MARCKS (myristoylated, alanine-rich C-kinase substrate), a major specific substrate for protein kinase C, has been studied in the rat brain. Light microscopic immunocytochemistry and biochemical analysis demonstrated that the protein is widespread throughout the brain and enriched in certain regions, including the piriform and entorhinal cortices, portions of the amygdaloid complex, the intralaminar thalamic nuclei, the hypothalamus, the nucleus of the solitary tract, nucleus ambiguus, and many catecholaminergic and serotonergic nuclei. Electron microscopic analysis revealed immunoreactivity in axons, axon terminals, small dendritic branches, and occasionally in dendritic spines. In neuronal processes, immunoreactivity was particularly prominent in association with microtubules, but reaction product was also seen in cytosol and adjacent to plasma membranes. No reaction product was observed in large dendrites, somata, or nuclei. A population of strongly immunoreactive glial cells was also observed. Many of these glial cells were morphologically similar to microglial cells, although some resembled astrocytes. In glial cells, both cytoplasm and plasma membranes were heavily labeled. The distribution of the MARCKS protein did not coincide precisely with the distribution of any of the subspecies of protein kinase C. The results indicate that the MARCKS protein is expressed in the majority of cell types in the CNS, and they suggest that the protein may be involved both in glial cell functions and in neuronal functions involving cytoskeletal elements in small dendritic branches and axon terminals. PMID- 2332804 TI - Scanning electron microscopic study of immunogold-labeled human leukocytes. AB - For many years critical point drying (CPD) has been the method of choice for preparing cells for scanning electron microscopy (SEM). Described herein is a simple, efficient, inexpensive, reproducible, and safe procedure using Peldri II, a proprietary fluorocarbon compound that is solid at room temperature and a liquid above 25 degrees C, as a sublimation dehydrant for processing specimens for SEM. The utility of Peldri II was demonstrated in studies using leukocytes from the blood of healthy donors and patients with leukemia as well as from long term lymphoblastoid cell lines. The application of the proposed Peldri II procedure was further documented in SEM studies in which the expression and distribution of the interleukin-2 receptor (IL-2R) on leukocyte surface membranes was imaged using colloidal gold-labeled antibodies (i.e., immunogold). When compared with current SEM preparation procedures using CPD, Peldri II is a useful alternative that is thought to offer several important advantages. PMID- 2332805 TI - Preparation of cross-sectional specimens of ceramic thermal barrier coatings for transmission electron microscopy. AB - During the microstructural examination of ceramic thermal barrier coatings by transmission electron microscopy (TEM), initial efforts for the preparation of cross-sectional thin foils from interface regions by conventional means were mostly failures. Delamination of the Y2O3-stabilized ZrO2 ceramic coating from the nickel-base alloy substrate sometimes occurred during fine polishing at around 80 microns thickness but mostly occurred during dimpling. Because of this sensitivity, special techniques for mechanical handling were developed so that ion milling could give thin enough regions of the metal-ceramic interface. TEM showed convincingly that the highly fragile nature of the coatings is in fact due to the extensive porosity at the interface developed as a result of heat treatment. PMID- 2332806 TI - Small colloidal gold conjugated to Fab fragments or to immunoglobulin G as high resolution labels for electron microscopy: a technical overview. AB - Fab-colloidal gold labelling in conjunction with negative staining and high resolution electron microscopy was used for targeting single protein units in regular arrays. These were bacteriophage T4 polyheads with Fab-Au2.5, and a specific antibody binding site on the haemagglutinin polypeptide of influenza virus with Fab-Au3, Fab-Au2.5, and Fab-Au1-2. For the latter, IgG-Au3 was also used. Experimental details are summarized to provide generally applicable methods for the preparation of small gold colloids Fab-Au and of labelling. The putative mechanism of protein-gold complex formation and adsorption to preferred sites on Fab and IgG, most probably to sulphur-rich regions, is discussed. The influence of pH during complex formation was found to be of minor importance in the samples investigated. Reported experimental details and our own experiences suggest that the importance of a protein's pI relative to its optimum gold complexing pH critically depends on the nature of the protein in question rather than being of general importance for protein-gold complex stability. PMID- 2332807 TI - Preparation of bone for high-voltage electron microscopic radioautography. AB - This paper presents a reliable technique for the preparation of radioautographic specimens for study by high-voltage electron microscopy. Tissues are fixed by ventricular perfusion of aldehydes, sectioned, collected on slides, and coated with nuclear track emulsion using a coating machine. Sections are developed after 17 weeks' exposure in either undiluted Microdol-X or diluted D-19 developer, fixed in 25% sodium thiosulfate, and stained through the emulsion with uranyl acetate in absolute methanol and aqueous lead citrate. The technique produces sections of even thickness and staining density with negligible numbers of background grains and non-specific labeling. In this report, the efficacy of this technique for the study of the periosteal surface of demineralized alveolar bone specimens is demonstrated. PMID- 2332808 TI - Microstructure and growth of ZnTe films. AB - The microstructure and growth of ZnTe films deposited onto glass and freshly cleaved NaCl substrates are carefully studied by a TEM. Effect of different stimulator on the grain growth is also described. PMID- 2332809 TI - Method for forming two-dimensional paracrystals of biological filaments on lipid monolayers. AB - A method is described for electron microscopic observation of two-dimensional paracrystals on unsupported lipid monolayers. The method uses a hydrophobic holey C-coated grid placed on a monolayer made positively charged by the inclusion of stearylamine (SA) and has been used to align scallop thin filaments and reconstituted actin/tropomyosin filaments to form paracrystals. The use of unsupported monolayers allows the paracrystals to be viewed in either negative stain or with cryoelectron microscopy. Those paracrystals in frozen hydrated specimens have better order than those with negative stain. It was found that varying the lipid composition between the less fluid distearolyphosphotidylcholine/SA and the more fluid egg yolk phosphotidylcholine/SA alters the size and order of the paracrystals, the more fluid system having smaller, more ordered paracrystalline domains. The advantage of the technique for studying actin/thin filaments is the ability to form large two-dimensional paracrystals under physiological conditions of [Mg2+] and pH. PMID- 2332810 TI - Quick-freeze, deep-etch replication of cells in monolayers. AB - We have made several technical improvements for quick-freeze, deep-etch replication of monolayers of cells grown on, or attached to, glass coverslips. Cells studied include muscle cells of rat and Xenopus cultured on glass coverslips, and erythrocytes attached to coverslips coated with poly-L-lysine. We describe methods for identifying particular areas of cultures, e.g., clusters of acetylcholine receptors on muscle cells, by light microscopy and then relocating these areas after replication. For good preservation of structure by quick freezing, it is necessary to ensure that the surface to be frozen is covered by a minimum depth of water (less than 10 microns). Insufficient or excess water left on the sample during freezing causes recognizable artifacts in its replica. We describe two ways to control the water table--one by improving visual control of water removal, the other by blowing excess water off the sample surface with a jet of nitrogen applied during its descent to the freezing block. Finally, we describe a new specimen holder that allows us to etch and replicate six samples at once with good thermal contact between the stage and samples. PMID- 2332811 TI - Improved cryoprotection and freeze-substitution of embryonic quail retina: a TEM study on ultrastructural preservation. AB - Conditions for cryofixation and freeze-substitution crucial to the ultrastructural preservation of embryonic quail retina were improved. As freeze substitution makes gentle dehydration and chemical fixation of tissue possible, the suitability of different cryoprotectants were tested in the preceding cryofixation. Additionally, different conditions for chemical prefixation were studied. In cryofixation, all of the "classic" cryoprotectants caused more or less severe tissue destruction. Only dimethylformamide (DMF) and--with certain reservations--dimethylsulfoxide (DMSO) yielded improved structure preservation. Perfusion fixation with a mixture of formaldehyde/glutaraldehyde (FA/GA) was superior to GA alone. In comparison to conventional fixation and dehydration methods, freeze-substitution yielded better ultrastructural preservation of the embryos with fewer artifacts. PMID- 2332812 TI - Lanthanum probing of cell membrane permeability in the rat heart: pathological versus artefactual alterations. AB - The influence of fixation on membrane permeability has been examined in the isolated rat heart using lanthanum as a permeability probe. Normal and ischaemic hearts were probed at various stages during a conventional fixation programme with either ionic or colloidal lanthanum and compared with lanthanum saline administered prior to fixation. Fixation of the myocardium coincident with or followed by lanthanum probing resulted in an influx of the probe into most myocytes in normal tissue. Alterations in permeability after ischaemic episodes could not be distinguished from the artefact. However, lanthanum saline prior to fixation showed exclusion of the probe from normal tissue, while the increased permeability demonstrated after ischaemia was associated with declining myocardial performance during subsequent reperfusion. These results illustrate the need for caution in the application and evaluation of methods determining permeability in fixed tissue. Probes of differing size and charge permeated fixed tissue to varying degrees thereby implicating the formation of specific lesions during chemical fixation. PMID- 2332813 TI - The hypertensive patient with multiple risk factors: clinical considerations. Satellite symposium to the Fourth European Meeting on Hypertension. 22 June 1989, Milan, Italy. Proceedings. PMID- 2332814 TI - Simvastatin in the treatment of hypercholesterolaemia in patients with essential hypertension. AB - Mortality from coronary artery disease is a common problem in treated hypertensive patients, and these people have a high prevalence of elevated cholesterol levels. A study was undertaken to determine whether cholesterol could be lowered effectively without major side effects in patients with treated hypertension. Forty-nine patients (mean age 67.6 years) with cholesterol greater than 5.5 mmol/l were placed on a reduced-fat (less than 30% of calories from fat with a ratio of polyunsaturated to saturated fats of less than 1) diet for 3 months. If the cholesterol was between 5.5 and 7.5 mmol/l and total cholesterol divided by high-density lipoprotein cholesterol was greater than 4.5, the patients were randomly allocated either to the simvastatin (24 patients) or the placebo group (25 patients). Diet and placebo caused minor and insignificant falls in cholesterol and no change in triglycerides or lipids. Treatment with simvastatin reduced cholesterol levels from 6.85 to 4.75 mmol/l (P less than 0.001), triglycerides from 2.7 to 2.1 mmol/l (P less than 0.01), low-density lipoproteins from 4.6 to 2.6 mmol/l (P less than 0.001) and high-density lipoproteins rose from 1.09 to 1.18 mmol/l (P less than 0.01). Total cholesterol divided by high-density lipoprotein cholesterol fell from 6.3 to 4.0 (P less than 0.001). The drug was well tolerated and the side-effect profile did not differ from the placebo in clinical or biochemical events. The active drug was stopped in one patient (abdominal pain, dizziness, headache, tiredness) and in two patients taking the placebo (elevated creatine phosphokinase, cardiovascular collapse). Simvastatin effectively lowered total cholesterol and improved the lipoprotein profile. The dose required in most patients was 40 mg/day. Simvastatin may be an acceptable drug to improve the lipoprotein profile in order to determine whether this improves the prognosis in patients treated for hypertension. PMID- 2332815 TI - Concepts of multiple risk factors management: the Gubbio study. AB - Treatment of hypertension has been one of the greatest medical successes of the last 30 years, but it has also suffered numerous drawbacks. These have probably arisen through failing to place antihypertensive treatment in the frame of a multiple strategy directed to the control of all major risk factors for cardiovascular disease. Indeed, there is increasing evidence from most of the controlled trials that treatment of hypertension is significantly less successful in smokers than in non-smokers, and in patients with elevated than in patients with normal plasma cholesterol. Consequently, when it was decided to start a new study on the epidemiology of hypertension in the town of Gubbio in Central Italy, the study was planned as one on the epidemiology of all established cardiovascular risk factors, with the primary target of determining how often various risk factors are simultaneously present in individuals within a typical and homogeneous community in Central Italy. PMID- 2332816 TI - Pathophysiology of proteinuria in diabetic glomerular disease. AB - Unchanged dextrans of graded size (28-60 A) were used to evaluate barrier size selectivity in 56 proteinuric patients with diabetic glomerular disease. Transglomerular sieving was enhanced selectively for dextrans of greater than 46 A radius. A mathematical model of hindered solute transport through a porous membrane showed that this finding reflected the development in the glomerular barrier of a subset of enlarged, non-discriminatory pores. Although few in number, these enlarged pores accounted for both the magnitude and the composition of the observed proteinuria. We conclude that impaired barrier size-selectivity underlies the proteinuria of diabetic glomerular disease, and that impairment of barrier charge-selectivity need not be invoked in this circumstance. PMID- 2332817 TI - Multiple risk factors in hypertension: results from the Gubbio study. AB - The association between hypertension and a number of cardiovascular disease risk factors was assessed in the large population sample of Gubbio, a town in central Italy that dates back to medieval times. The data confirm those of previous studies showing that hypertension is strongly associated with other metabolic abnormalities, such as markedly overweight subjects, hyperuricaemia, hyperglycaemia, hypercholesterolaemia, that may be related to the aetiopathogenesis of high blood pressure and, in addition, compound the risk of major clinical cardiovascular events in people with hypertension. The findings are therefore relevant for prevention strategies. In addition, the association between erythrocyte sodium-stimulated lithium countertransport and hypertension is being studied. PMID- 2332819 TI - Art therapy with bereaved youth. PMID- 2332818 TI - Home-based palliative care for children--Part 1: The institution of a program. AB - To assess the necessity and feasibility of introducing a home-based palliative care program for children admitted to our neurosurgical unit and diagnosed as being terminally ill, we conducted an analysis of all such patients admitted to our unit over an 18-month period. Of a total of 30 patients, 22 (73.4%) had central nervous system tumors, 6 (20.0%) had myelomeningocele/hydrocephalus, and 2 (6.6%) had arteriovenous malformations. The mean duration +/- SEM of hospitalized days prior to death and the proportion of time spent hospitalized during the terminal phase of illness were 28.8 +/- 4.77 and 0.327 respectively, for the 23 patients who died and on whom adequate data were available. Sixteen (70.6%) of these 23 patients died in hospital. Nine (30.0%) of the total group of patients were studied prospectively during the last 6 months of this study to determine the extent of their symptoms and to ascertain whether it would be feasible for them to be managed at home. The most troublesome symptoms in this subgroup were feeding difficulties, gastrointestinal symptoms, breathing difficulty, and seizures. These symptoms were managed either by (a) medications administered orally or by feeding tube or rectally, or by (b) noninvasive procedures carried out by a nurse under the direction of the admitting neurosurgeon. This study suggests that prolonged hospitalization for children diagnosed as being terminally ill can be avoided by introducing a home-based palliative program with involvement from a nurse and a physician familiar with drug therapy for terminally ill children. PMID- 2332820 TI - AIDS and palliative care: an individual appeal to health care professionals and intervening parties. PMID- 2332821 TI - Euthanasia--taking a stand. PMID- 2332822 TI - Heroic self-healing and cancer: clinical issues for the health professions. AB - Increasingly over the last few decades, persons with cancer are being cured or surviving longer. As a result, the popular press has given more attention to the possibilities for "beating" cancer. The role of personal control in overcoming cancer has been promoted via a heroic formula that includes positive thinking, healing imagery, and personal growth. Empirical support for a psychospiritual influence on cancer illness is tenuous. Nevertheless, the psychological implications of belief in such influence are important in their own right. In this paper, the positive and negative consequences for patients of popular conceptions of the heroic cancer survivor are explored. Clinical and ethical issues related to the health professional's responses to patients' belief in heroic self-healing are discussed, and a rationale is presented for adopting a non-judgmental, person-centered approach. PMID- 2332823 TI - Comparison of beliefs and practices of ethnic Viet and Lao Hmong concerning illness, healing, death and mourning: implications for hospice care with refugees in Canada. AB - This research paper examines the background, cosmology, and health, illness, healing, death, and mourning-related beliefs and practices of two groups of refugees in Canada, the ethnic Viet and the Lao Hmong. Emphasis is placed on the syndrome of uprootedness among refugees which exacerbates the patient's sense of loss in the palliative care setting. Practical recommendations to improve care of these patients and their families are made. PMID- 2332824 TI - Pressure sores and optimum skin care. PMID- 2332825 TI - Witness through time. PMID- 2332826 TI - The role of volunteers in alleviating grief. PMID- 2332827 TI - [Calendula arvensis L. Impact of saponins on toxicity, hemolytic effect, and anti inflammatory activity]. AB - The study of the chemical composition of Calendula arvensis var. eu arvensis Maire reveals the presence of saponins. These saponins confer a haemolytic property on the plant. In our work we have, first determined the saponin responsible for the haemolytic property; and then we have studied the impact of the saponins on the acute toxicity and the anti-inflammatory activity induced by carrhageenin oedema. PMID- 2332828 TI - Medial calcaneal nerve. An anatomical study. AB - The authors studied the medial calcaneal nerve of the human foot to determine its precise origin and to establish in detail its course and distribution. Its origin and distribution were compared to those of the inferior calcaneal nerve, and the importance of the nerve in the diagnosis of heel pain was reviewed. The authors concluded that the medial calcaneal nerve occurs in all subjects. Its origin is variable, arising from either the tibial nerve or the lateral plantar nerve after the bifurcation of the former. It innervates the flexor retinaculum and the skin of the heel pad. Therefore, it is clinically a source of pain perception in the heel. PMID- 2332829 TI - Management of complex pedal cutaneous larva migrans. AB - Although cutaneous larva migrans is more commonly seen in the southeastern US and tropical regions of the world, patients with such parasitic involvement may present in other non-endemic areas for various reasons, particularly travelers returning from tropical vacations. Awareness of the clinical presentation and symptomatology of cutaneous larva migrans is important for all physicians, including those practicing in northern climates, for prompt recognition and effective treatment of the disease. Furthermore, cutaneous larva migrans should be of particular interest to podiatrists, because the infestation commonly involves the feet, and a patient may initially present for treatment of secondary manifestations, ie, dermatitis, pruritus, or infection, as in this case report. PMID- 2332830 TI - Kyrle's disease. A rare case report and surgical treatment. PMID- 2332831 TI - Management of diabetic plantar ulcers with a walking brace. A clinical trial. PMID- 2332832 TI - A public health perspective on podiatric medicine. PMID- 2332833 TI - Effects of orthoses on selected physiologic parameters in cycling. PMID- 2332834 TI - Subungual exostosis. PMID- 2332835 TI - [Effect of intracellular organic phosphates on erythrocyte deformability]. AB - Organic phosphates in human erythrocytes were selectively varied by incubating fresh human erythrocytes in phosphate-buffered saline containing inosine, pyruvate, adenine, and/or adenosine in various concentrations. The deformability of erythrocytes was measured at 24 degrees C with a rheoscope under shear stress of 8-82 dyn/cm2. (1) With increasing 2, 3-DPG (5 approximately 15 mM/l cells), undeformable erythrocytes increased due to the increased mean corpuscular hemoglobin concentration (MCHC). However, these cells became deformable, when the MCHC was reduced by suspending in hypotonic medium. (2) At the same MCHC, the deformability of 2, 3-DPG-enriched erythrocytes was still reduced, compared with that of control erythrocytes, probably due to altered membrane viscoelastic properties. (3) 2, 3-DPG-reduced erythrocytes (2.2 mM/l cells) was not altered in their deformability. (4) Deformability of 2, 3-DPG-enriched erythrocytes was not changed by lowering oxygen tension. (5) Deformability of erythrocytes was not affected by varying intracellular ATP in the range of 0.5 approximately 2.2 mM/l cells (ATP in control cells was 1 mM/l cells). (6) Increment of IMP (approximately 0.9 mM/l cells) and ITP (approximately 0.5 mM/l cells) did not alter the deformability of erythrocytes. (7) Interaction of intracellular organic phosphates with membrane proteins was discussed. PMID- 2332836 TI - [Visual evoked potential in guinea pigs]. AB - The present study was designed to establish visual evoked potential (VEP) as one of clinical tests for veterinary medicine. Experiments were carried out on eight adult male guinea pigs weighed 350 to 750 g. We investigated influences of click sound, luminous intensity and habituation on VEP patterns. The VEP of the guinea pig was composed of primary (P 10, N 20, P 30, N 40) and secondary (P 55, N 75, P 100, N 140) components, followed by a rhythmic after-discharge. Click sound with flash produced some unclear peaks in VEP, while click sound without flash elicited clear six peaks. These different components of the response to stimulation suggested that the acoustically evoked potential induced some peaks in VEP. With the intensity used in the present study, changes in luminous intensity resulted in unrecognizable difference among the VEPs. Early components of VEP were not clearly influenced by the habituation to stimulation. As the stimulation was repeated, rhythmic after-discharge seemed to be suppressed in the half of experiments. PMID- 2332837 TI - Convergence of temporal and spectral information into acoustic images of complex sonar targets perceived by the echolocating bat, Eptesicus fuscus. AB - 1. FM echolocating bats (Eptesicus fuscus) were trained to discriminate between a two-component complex target and a one-component simple target simulated by electronically-returned echoes in a series of experiments that explore the composition of the image of the two-component target. In Experiment I, echoes for each target were presented sequentially, and the bats had to compare a stored image of one target with that of the other. The bats made errors when the range of the simple target corresponded to the range of either glint in the complex target, indicating that some trace of the parts of one image interfered with perception of the other image. In Experiment II, echoes were presented simultaneously as well as sequentially, permitting direct masking of echoes from one target to the other. Changes in echo amplitude produced shifts in apparent range whose pattern depended upon the mode of echo presentation. 2. Eptesicus perceives images of complex sonar targets that explicitly represent the location and spacing of discrete glints located at different ranges. The bat perceives the target's structure in terms of its range profile along a psychological range axis using a combination of echo delay and echo spectral representations that together resemble a spectrogram of the FM echoes. The image itself is expressed entirely along a range scale that is defined with reference to echo delay. Spectral information contributes to the image by providing estimates of the range separation of glints, but it is transformed into these estimates. 3. Perceived absolute range is encoded by the timing of neural discharges and is vulnerable to shifts caused by neural amplitude-latency trading, which was estimated at 13 to 18 microseconds per dB from N1 and N4 auditory evoked potentials in Eptesicus. Spectral cues representing the separation of glints within the target are transformed into estimates of delay separations before being incorporated into the image. However, because they are encoded by neural frequency tuning rather than the time-of-occurrence of neural discharges, the perceived range separation of glints in images is not vulnerable to amplitude-latency shifts. 4. The bat perceives an image that is displayed in the domain of time or range. The image receives no evident spectral contribution beyond what is transformed into delay estimates. Although the initial auditory representation of FM echoes is spectrogram-like, the time, frequency, and amplitude dimensions of the spectrogram appear to be compressed into an image that has only time and amplitude dimensions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2332838 TI - The influence of the auditory cortex on acoustically evoked cerebellar responses in the CF-FM bat, Rhinolophus pearsonic chinesis. AB - 1. Acoustically evoked responses of 284 neurons isolated from the cerebellar vermis, hemispheres and paraflocculus of Rhinolophus pearsonic chinesis were studied under free field acoustic stimulation conditions. 2. The BFs of these cerebellar auditory neurons ranged from 24 to 76 kHz but they mostly fall either between 48 and 64 kHz or between 65 and 76 kHz. However, the BF distribution varies among vermal, hemispheric and parafloccular neurons. 3. Threshold curves of cerebellar neurons are generally broad but those tuned to the frequency of the predominant CF component are extremely narrow. 4. Response latencies of cerebellar neurons ranged from 2 to 48 ms suggesting multiple auditory cerebellar pathways. The latency distribution also varies among vermal, hemispheric and parafloccular neurons. 5. Although both the vermis and hemispheres contain a disproportionate number of 65-74 kHz neurons, the response latencies of those neurons isolated from the vermis are scattered over a wide range of 2.2-28 ms while those neurons isolated from the hemispheres are generally stabilized between 5 and 12 ms. 6. Electrical stimulation of the auditory cortex evokes discharges from a recorded cerebellar auditory neuron. Cortical stimulation also facilitates the response of an acoustically evoked cerebellar neuron by increasing its number of impulses. The degree of facilitation is dependent upon the amplitude of the acoustic stimulus. 7. For a given electrical and acoustic stimulation condition, the facilitative latency and the degree of facilitation varied with the interstimulus interval. Among 23 neurons studied, most of them (19 neurons, 82.6%) had a maximal facilitative latency between 2 and 10 ms. 8. By examining the difference in the facilitative effect in each isolated cerebellar auditory neuron before and after a topical application of local anesthetic, procaine, onto the point of electrical stimulation in the auditory cortex, we found that the facilitative pathways to vermal and hemispheric neurons may be different from the pathway to parafloccular neurons. 9. Possible auditory pathways to different parts of the cerebellum are discussed in relation to the wide range of recorded response latencies. 10. The facilitative influence of the auditory cortex on the cerebellar auditory neurons is assumed to enhance the cerebellar role in acoustic motor orientation. PMID- 2332839 TI - Encoding of a spectrally-complex communication sound in the bullfrog's auditory nerve. AB - 1. A population study of eighth nerve responses in the bullfrog, Rana catesbeiana, was undertaken to analyze how the eighth nerve codes the complex spectral and temporal structure of the species-specific advertisement call over a biologically-realistic range of intensities. Synthetic advertisement calls were generated by Fourier synthesis and presented to individual eighth nerve fibers of anesthetized bullfrogs. Fiber responses were analyzed by calculating rate responses based on post-stimulus-time (PST) histograms and temporal responses based on Fourier transforms of period histograms. 2. At stimulus intensities of 70 and 80 dB SPL, normalized rate responses provide a fairly good representation of the complex spectral structure of the stimulus, particularly in the low- and mid-frequency range. At higher intensities, rate responses saturate, and very little of the spectral structure of the complex stimulus can be seen in the profile of rate responses of the population. 3. Both AP and BP fibers phase-lock strongly to the fundamental (100 Hz) of the complex stimulus. These effects are relatively resistant to changes in stimulus intensity. Only a small number of fibers synchronize to the low-frequency spectral energy in the stimulus. The underlying spectral complexity of the stimulus is not accurately reflected in the timing of fiber firing, presumably because firing is 'captured' by the fundamental frequency. 4. Plots of average localized synchronized rate (ALSR), which combine both spectral and temporal information, show a similar, low-pass shape at all stimulus intensities. ALSR plots do not generally provide an accurate representation of the structure of the advertisement call. 5. The data suggest that anuran peripheral auditory fibers may be particularly sensitive to the amplitude envelope of sounds. PMID- 2332840 TI - Who are we? Low self-esteem and marital identity. PMID- 2332841 TI - The nursing care challenge. Borderline patients. PMID- 2332842 TI - Colorado Society of Clinical Specialists in Psychiatric Nursing. Ethical guidelines for accountability. PMID- 2332843 TI - Malingering. PMID- 2332844 TI - Anxiety treatment. PMID- 2332845 TI - Seclusion & restraint. PMID- 2332846 TI - Assessing child abuse: the TRIADS checklist. AB - Although all types of abuse injure children, psychological abuse is most elusive and damaging on many levels, particularly levels of attachment, affective development, and the evolution of empathetic capacities that allow a child to receive and transmit, in an appropriate manner, emotional information between people. Some think that this type of psychological abuse coupled with neglect and perhaps early physical abuse impairs the child's total capacity to respond emotionally (Brothers, 1989). Essentially, empathy is a matter of a complex informational processing activity. Alexithymia, an inability to perceive the emotions of others, has been linked in primate studies to deprivation (Sackette, 1966). This awareness of the impact of environmental factors on the development of critical emotional and ultimately interpersonal regulating mechanisms underscores the need to attend to all aspects of child abuse. PMID- 2332847 TI - The fat on the joint: osteoarthritis and obesity. PMID- 2332848 TI - Food induced ("allergic") arthritis: inflammatory synovitis in rabbits. AB - Progress in understanding rheumatoid (RA) and inflammatory arthritis has been limited in part because there has been no widely accepted animal model of naturally occurring human disease and because the clinical syndrome of RA may reflect the expression of multiple etiologies. We have considered that inflammatory joint disease may be induced and/or exacerbated by food related antigens. To facilitate our investigations, we studied inflammatory synovitis in rabbits induced by oral exposure to environmental antigens. In our preliminary experiments, we examined 9 Florida White, 30 New Zealand White, and 9 Old English rabbits. They were nourished with normal rabbit chow supplemented with either water or cow's milk beginning at age 7 to 26 weeks and observed for 81 to 204 days. Animals were then sacrificed. Histological sections of the knees were examined and graded in a blinded fashion for synovial cell hyperplasia, inflammation, and lymphoplasmocytic infiltration. In addition, serum levels of IgG antimilk, IgG antibovine serum albumin, IgG anticasein, and IgG-C3 complexes were quantified. We found no abnormalities among Florida White rabbits but observed histological synovitis in 53% of the milk fed New Zealand White (9/17), 40% of the water fed Old English (2/5), and all of the milk fed Old English rabbits (4/4) (p = 0.05, milk fed vs water fed animals). Milk fed animals had significantly (p less than 0.0005) greater levels of antibodies and complexes than water fed animals. Our data suggest that environmental antigens may be arthritogenic for some rabbit strains. These observations may provide an important model for the study of inflammatory joint disease analogous to oral, environmental antigen exposure in man. PMID- 2332849 TI - Food induced ("allergic") arthritis: clinical and serologic studies. AB - These studies sought to confirm our recent report of a patient with rheumatoid like arthritis (RA) with clinical and immunologic milk sensitivity, to assess the prevalence of food related rheumatic symptoms, and to identify clinical and serological features of these patients. Thirty percent of our patients with RA alleged food related ("allergic") arthritis. Sixteen patients have now completed 19 double blind, controlled food challenge studies: 3 demonstrated subjective and objective rheumatic symptoms after double blind, encapsulated food challenges. The 3 were virtually asymptomatic when receiving elemental nutrition or not taking the offending foods. One was our milk sensitive patient who had increased IgG4 anti-alpha-lactalbumin, IgG-milk complexes, and delayed skin and cellular reactivity to milk; one developed inflammatory synovitis after shrimp ingestion and had increased IgG antishrimp; and another was a cardiac care unit (CCU) nurse who experienced rheumatic symptoms after exposure to nitrates. All were seronegative with palindromic symptoms and nonerosive disease. IgG, G4, A, M, and E antifood, Ig-food immune complexes, and in vitro cellular reactivity to foods were not otherwise distinctively abnormal in these or other patients with rheumatic diseases. Thus most patients alleging food induced rheumatic symptoms did not show these on blinded challenge, but some did. Probably not more than 5% of rheumatic disease patients have immunologic sensitivity to food(s). Such patients have been identified only by controlled challenge studies. These observations suggest a role for food allergy in at least some patients with rheumatic disease. PMID- 2332850 TI - Impact of NSAIDS on murine antigen induced arthritis. II. A light microscopic investigation of antiinflammatory and bone protective effects. AB - The impact of daily, orally administered nonsteroidal antiinflammatory drugs (NSAID) or a steroid on arthritic knee joints of mice with 1-3 weeks of antigen induced arthritis (AIA) was examined by light microscopy. Prophylactic drug effects on inflammatory cell infiltrate in synovium and joint cavity were evident only in mice treated with prednisolone (0.2-5.0 mg/kg). Treatment with diclofenac, piroxicam (both 0.5-7.5 mg/kg) or tiaprofenic acid (3-30 mg/kg) did not change these phlogistic features significantly. Striking, however, was the protective effect of piroxicam on bone apposition, a common trait in murine AIA. Among the other drugs, minor antiosteophyte effects were exerted only by prednisolone. Histological assessment was also performed on osteocyte death which was almost exclusively confined to menisci and tibial subchondral bone. Because of variability in occurrence and intensity, no clear picture emerged from drug effects on this lethal feature. Combined data from this and a previous pharmacological study, directed at chondroprotective effects, points to prednisolone as the best antiinflammatory and joint protective drug. PMID- 2332851 TI - Sex hormone involvement in the induction of experimental systemic lupus erythematosus by a pathogenic anti-DNA idiotype in naive mice. AB - The effect of sex hormones on the induction of experimental systemic lupus erythematosus (SLE) with a human anti-DNA (16/6 Id +) antibody, was studied. We found that injection of the pathogenic idiotype to BALB/c females and orchiectomized males treated with estrogen caused a rapid outburst of the disease 3 months after immunization, while nonestrogen treated mice developed the disease 5 months after immunization. The flare of SLE disease was characterized by raised levels of autoantibodies in the sera to dsDNA, histones, cardiolipin, Sm, RNP, SSA (Ro), SSB (La) and an emergence of high titers of mouse antibody carrying the 16/6 Id. These enhanced antibody levels were associated with an increase in erythrocyte sedimentation rate, proteinuria and leukopenia. Immunofluorescent studies confirmed the existence of immune complexes in the afflicted kidneys. Testosterone treated BALB/c females and orchiectomized males developed a classical response to the human anti-DNA antibody (16/6 Id +), but failed to develop fulminant SLE-like disease. Our data demonstrate the importance of sex hormones on the induction of experimental SLE-like disease in mice with no genetic tendency to autoimmunity. PMID- 2332852 TI - Major salivary gland function in primary Sjogren's syndrome and its relationship to clinical features. AB - Unstimulated and stimulated salivary secretions of both the parotid and submandibular/sublingual glands were studied in 64 patients with primary Sjogren's syndrome to define further salivary changes in this disorder. The stimulated flows of the submandibular/sublingual glands were below normal in 56 of 64 patients, while stimulated parotid flows were decreased in only 35. Compositional changes of the submandibular saliva paralleled changes of parotid saliva, and these data suggest that ductal electrolyte resorption is altered in the glands of patients. Finally, stimulated parotid flow rates correlated inversely with focus scores of the minor salivary gland biopsies. PMID- 2332853 TI - Normal immune responses in systemic sclerosis. AB - Cellular and humoral immune responses were assessed in 24 patients with systemic sclerosis and matched controls by immunization with a thymus dependent (TD) antigen, keyhole limpet hemocyanin (KLH), a and thymus independent (TI) antigen, dinitrophenylated Ficoll (DNP-Ficoll). Cell mediated immunity in the patients with systemic sclerosis expressed as delayed cutaneous hypersensitivity to KLH, as well as the primary T dependent and T independent antibody responses were normal. Our findings suggest that there is no generalized defect in the immune responsiveness of patients with systemic sclerosis. There is however evidence that specific defects may occur in certain subsets of patients with systemic sclerosis. PMID- 2332854 TI - C4 null genes in American whites and blacks with myositis. AB - The frequencies of C4A and C4B alleles were determined in 66 adults with myositis in relation to HLA class I and II. In whites with myositis, the C4A*Q0 allele occurred in 13/31 (47%) as compared to 25/101 (25%) normal controls (p = 0.08, relative risk = 2.7). Only 11/35 (31%) of black patients with myositis had a C4A*Q0 allele compared to 11/55 (20%) of controls (p = NS, RR = 1.8). Thus, the MHC class III genes do not appear to be the primary genetic risk factors for myositis in adults. PMID- 2332855 TI - Destructive hip lesions in seronegative spondyloarthropathies: relation to gut inflammation. AB - In the seronegative spondyloarthropathies the hip lesions can be subdivided into a concentric type progressing to ankylosis and an eccentric type leading to joint destruction. Radiologic examination of the hips was performed in 177 of 211 patients suffering from seronegative spondyloarthropathies on whom ileocolonoscopy with biopsies of ileum and colon was performed; in 27 of these 177 patients, hip lesions were demonstrated. The concentric form seems to be radiologically, clinically and genetically more related to axial involvement; moreover, the frequency of subclinical gut inflammation was the same as in the group of patients with ankylosing spondylitis (AS) without peripheral arthritis, and thus significantly lower than in patients with AS with peripheral arthritis. Eccentric, destructive hip lesions seem to be unrelated to axial involvement, but they are associated with the presence of HLA-Bw62 and gut inflammation (100%), mainly of the chronic, Crohn disease-like type. PMID- 2332856 TI - Pressure induced deformation of the interstitial route across synovium and its relation to hydraulic conductance. AB - The ease with which fluid passes across the synovial lining (i.e., the lining's hydraulic conductance) is enhanced when intraarticular fluid pressure (IAP) is raised acutely to pathological levels in rabbit knees. A structural basis for this pathophysiological change was sought by morphometry of synovial sections from rabbit knees fixed in situ at less than or equal to 5 cm H2O and 25 cm H2O IAP. Light and electron microscopy showed that the main structural changes induced in areolar synovium by raising IAP to 25 cm H2O were (1) a reduction in synovial thickness to 56% control value; (2) an increase in the area of interstitium exposed at the synovial surface (3) an increased proximity of the synovial capillaries to the joint lumen, the mean distance of capillaries from the surface falling from 8.9 +/- 0.5 microns (n = 391) to 3.3 +/- 0.3 microns (n = 92: p less than 0.001). The capillary profiles showed slight compression under 25 cm H2O IAP, but no collapse. The ratio of interstitial area to thickness is the geometric factor governing hydraulic conductance. The maximum change in interstitial area/thickness was 6.8 times for the blood-joint barrier. A change of this magnitude accounts partly (but not fully) for the experimentally observed conductance changes; and it highlights the importance of capillary depth as a factor governing exchange in joints. PMID- 2332857 TI - Oligolamellar nature of the articular surface. AB - The osmiophilic lining of the articular surface has been studied by electron microscopy and shown to be oligolamellar phospholipid by employing special nondestructive fixation procedures. This finding was confirmed using hydrophobic probes in epifluorescence microscopy and by other simple tests of hydrophobicity. Oligolamellar phospholipid was also observed within the subchondral matrix while lamellar bodies, phospholipid in its most surface-active state, were found in the type of canals which can result from superficial fibrillation. The results are discussed as consistent with a previously proposed hypothesis whereby joints are lubricated by shearing between surface lamellae of phospholipid just as occurs in graphite when writing with a pencil. PMID- 2332858 TI - Distinct cartilage proteoglycan chromatographic elution patterns in advanced human hip osteoarthritis: correlations with histologic analysis. AB - Articular cartilage explants were derived from 14 human osteoarthritic (OA) femoral heads. Newly synthesized, 35SO4 radiolabeled proteoglycans and endogenous uronic acid containing proteoglycans present in the extracellular matrix fell into one of 4 distinct patterns of elution on Sepharose CL-2B chromatography under associative conditions. There was a strong correlation between the elution patterns for newly synthesized and endogenous proteoglycans within a given hip specimen (p = 0.005). The proteoglycan elution pattern also strongly correlated when Day 1 and Day 20 explants were compared. The presence of a distinct subpopulation of hydrodynamically small proteoglycan (Kav, 0.6-0.9) correlated with a loss of both pericellular and extracellular matrix metachromasy in histologic sections of cartilage (p = 0.018). Our findings support the contention that different biochemical-histological subsets exist in "end-stage" hip OA. PMID- 2332859 TI - Rhythmic variations in pain perception in osteoarthritis of the knee. AB - Twenty patients with primary osteoarthritis (OA) of the knee completed self administered questionnaires probing pain severity on 10 occasions every day for 7 consecutive days. Rhythmometric analyses detected a significant circadian rhythm in pain in the majority of patients. Our data suggest that perceived pain severity varies substantially with time of day. These observations have important implications for the administration of pain questionnaires as outcome measures for clinical trials of nonsteroidal antiinflammatory drugs in OA of the knee. PMID- 2332860 TI - Recurrence of adult Still's disease after pregnancy. AB - A 35-year-old white woman had recurrent episodes of adult onset Still's disease after 2 successive pregnancies. The second episode was characterized by an erythematous, macular rash, arthritis, fevers and hepatic dysfunction which occurred 2 months postpartum. The recurrent illness after pregnancy suggests that adult onset Still's disease may be influenced by gestational status. PMID- 2332861 TI - Successful treatment of refractory systemic lupus erythematosus with intravenous immunoglobulins. AB - Two cases of refractory systemic lupus erythematosus (SLE) were successfully treated with intravenous immunoglobulins (IVIg). In Case 1, the immediate recovery from severe pancytopenia and the improvement of proteinuria were observed, following IVIg therapy in high doses (450 mg/kg) for 5 consecutive days. In Case 2, 3 courses of IVIg therapy (100 mg/kg) for 6 to 8 days resulted in a significant reduction of massive proteinuria. In both cases, the improvement of immunological variables was also seen. PMID- 2332862 TI - Burkitt's lymphoma in a patient with systemic lupus erythematosus. AB - Patients with systemic lupus erythematosus (SLE) appear to be at increased risk for development of neoplastic disease. We describe the case of a male teenager with SLE and Burkitt's lymphoma. His presentation was similar to that of an exacerbation of his underlying SLE. We believe this to be the first case of Burkitt's lymphoma in a patient with SLE. The association of SLE and malignancy, with emphasis on lymphoproliferative states, is discussed. PMID- 2332863 TI - Erythema nodosum and non-Hodgkin's lymphoma. AB - We describe a case of erythema nodosum associated with non-Hodgkin's lymphoma. The course and resolution of the erythema nodosum correlated most closely with a breakdown and release of new antigen at the start of a new regimen of chemotherapy. PMID- 2332864 TI - Intravenous pulse methylprednisolone for the treatment of a child with Sjogren's nephropathy. AB - Six years after the onset of polyarthritis and after several episodes of recurrent parotitis, our patients developed the abrupt onset of renal insufficiency. Kidney histopathology showed interstitial and peritubular lymphocytic infiltration typical of Sjogren's nephropathy. Treatment with high dose intravenous methylprednisolone resulted in rapid and sustained normalization of kidney function. The favorable response of our patient to intravenous pulse corticosteroids suggests that this therapy is effective for the treatment of Sjogren's nephropathy. PMID- 2332865 TI - Re: Age of death of parents for patients with RA. PMID- 2332866 TI - Radiographic changes in early rheumatoid arthritis. PMID- 2332867 TI - RS3PE syndrome. PMID- 2332868 TI - Pulmonary hypertension in systemic lupus erythematosus. PMID- 2332869 TI - The neonatal lupus erythematosus associated with isolated LA(SSB) antibodies. PMID- 2332870 TI - Host specificity of Strigiphilus owl lice (Ischnocera: Philopteridae), with the description of new species and host associations. AB - Three new species and 11 new host associations are described for the cursitans species group of the genus Strigiphilus, the only genus of Mallophaga confined to owls (Strigiformes). The new species are S. schemskei ex Bubo coromandus, S. garylarsoni ex Otus leucotis, and S. petersoni ex Ninox punctulata. This paper completes a taxonomic review of the cursitans species group and includes an updated host-parasite list. The host specificity of the group is reviewed, including features of the natural history of lice and their hosts that may have influenced the evolution of host-parasite associations. Although most members of the cursitans group are host specific, several cases of secondary transfer among ecologically related hosts are apparent. The significance of such transfers is discussed in light of attempts to employ data on host-parasite associations for host systematics. PMID- 2332871 TI - The genus Hoplopleura (Anoplura: Hoplopleuridae) from murid rodents in Sulawesi, with descriptions of three new species and notes on host relationships. AB - Hoplopleura chrysocomi, H. sembeli, and H. musseri are described and illustrated as new species from bioendemic murid rodents, and H. pacifica Ewing is documented from commensal murids from Sulawesi Utara, Indonesia. H. chrysocomi parasitized only Bunomys chrysocomus (Hoffmann), and H. musseri was taken only from Maxomys musschenbroeki (Jentink). H. sembeli was collected from three species of sympatric murids but parasitized principally Maxomys hellwaldi (Jentink). Similarities between H. musseri from Sulawesi and H. pectinata (Cummings) from mainland Southeast Asia and Borneo corroborate host taxonomies that propose close phylogenetic relationships between their spiny rat hosts. Brief comment is made on possible coevolution between the regionally bioendemic Sulawesi macaques and their pedicinid sucking lice. PMID- 2332872 TI - Host-seeking behavior of adult Ixodes pacificus (Acari: Ixodidae) as determined by flagging vegetation. AB - Diurnal host-seeking by adults of the western black-legged tick, Ixodes pacificus Cooley & Kohls in relation to vegetative habitat type and meterological factors was investigated at a coastal and an inland site in northern California. Host seeking behavior and relative tick abundance were determined with a tick drag method from late fall to midwinter 1987-1988. At the inland site, tick abundance usually was significantly greater in chaparral-grassland ecotones than in adjoining dense chaparral on the south-facing slope of a mountaintop, whereas both of these vegetative types produced significantly fewer ticks on a north slope compared with a contiguous south-facing slope. There was no evidence for an association between tick abundance and plant species within ecotonal chaparral. Multiple regression analyses revealed that tick abundance in ecotonal chaparral at the inland site and in grassland at the coastal site was not associated consistently with either ambient temperature or relative humidity. Compared with the inland site, ticks were considerably more abundant at the coastal site where sampling occasionally yielded more than 100 ticks per 100 drag samples. The incidence of infection with Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, the etiologic agent of Lyme borreliosis, in adult ticks collected in the morning (1.5%) versus afternoon (2.2%), and in male (1.3%) versus female ticks (2.5%), at the coastal site in winter was similar. PMID- 2332873 TI - Classification of screwworms (Diptera: Calliphoridae) by larval spine morphology. AB - The morphology of screwworm, Cochliomyia hominivorax (Coquerel), larval spines was affected by larval substrate and geographic effects on variation. Spine morphology of individual larvae was used to determine criteria for discrimination analysis classification. Classification criteria for types of wounds and host species were determined for larvae from central and southern Mexico. Larvae from marginal populations (United States, Caribbean Islands, Costa Rica) were classified by these criteria. Classifications were 27% accurate for wound type and 20% correct for animal species. When single egg masses were split and larvae were reared on laboratory diet and animal substrates, analysis of spine types showed significant rearing environment and sibship (egg mass) effects. Cluster analysis of geographic groups showed that larvae from central populations were closely clustered, whereas marginal groups were morphologically dissimilar from each other and from the central populations. These results indicate that larval spine morphology has limited value in taxonomic or systematic studies of screwworms and that mating compatibility was not related to spine similarity among populations. The significant differences between wound-reared and artificial media-reared larvae indicate that differences in spine morphology could be used to verify that samples from the field were indeed taken from animal wounds. PMID- 2332874 TI - Changes in free amino acid concentration in the hemolymph of the female Culex pipiens pallens (Diptera: Culicidae), after a blood meal. AB - The analysis of the free amino acids in the hemolymph of female Culex pipiens pallens L. indicated that asparagine, glutamine, glycine, leucine, serine, threonine, tyrosine, and valine noticeably increased in concentration during a blood meal digestion at 22 degrees C. The concentrations started to rise at about 4 h, reaching maximal level at 12-24 h, and then gradually returned to the prefeeding level by the fifth day after the blood meal. Before the sharp increase, the concentrations of asparagine, glutamine, glycine, serine, threonine, and tyrosine declined slightly during the first 1-2 h, probably because of hemolymph dilution by water absorbed from the blood meal. Histidine and lysine also showed a minor decrease soon after blood feeding, followed by a moderate but noticeable increase, delaying maximal concentrations until 48 h after the blood meal. Proline and alanine both exhibited a high hemolymph content and changed greatly, but with a large variation between the two samples analyzed. The changing pattern of individual hemolymph amino acids depended to a large extent upon the content of each amino acid in the blood meal given to the mosquitoes. Other free amino acids detected in the hemolymph were at very small concentrations and except for phenylalanine did not show any changes after a blood meal. The total free amino acid concentration was 50 nmol (or 6 micrograms) per microliters hemolymph before a blood meal, and increased to a maximal concentration of 88 nmol (or 11 micrograms) per microliters hemolymph at 18 h after the blood meal. PMID- 2332875 TI - Ticks (Acari: Ixodidae) of the Nile monitor on Rusinga Island, Kenya. AB - In the course of a study of ticks of livestock, five Nile monitor lizard specimens were caught and examined for ticks. Although none of the tick species infesting livestock were found on the reptiles, a large number of adults and presumed nymphs and larvae of Aponomma flavomaculatum (Lucus) and adults of Amblyomma sparsum (Neumann) were collected. The ticks demonstrated a distinct predilection for their attachment sites. This is the second report of A. flavomaculatum from this part of Kenya. PMID- 2332876 TI - Histological reactions to bites of Amblyomma variagatum and Rhipicephalus appendiculatus (Acari: Ixodidae) fed simultaneously on naive or sensitized rabbits. AB - Histopathological studies on attachment sites of nymphs, 48 h after attachment on three groups of rabbits, have revealed differences that were related to the rabbits' previous tick experience. Feeding lesions caused by Amblyomma variegatum (F.) in tick-naive rabbits were extensive and the total number of inflammatory cells was about 10 times greater than that in the feeding lesions caused by Rhipicephalus appendiculatus Neumann fed simultaneously on contralateral ears. Rabbits that were previously sensitized either to A. variegatum or R. appendiculatus by repeated tick infestations showed epidermal vesiculation and significant mobilization of eosinophils at the homologous tick feeding sites, events that did not occur with tick-naive rabbits. The feeding of A. variegatum nymphs on rabbits sensitized to R. appendiculatus produced a similar type of intense reaction, but the cellular responses to R. appendiculatus in the skin of rabbits sensitized to the A. variegatum were negligible. PMID- 2332878 TI - Effects of larval population density on rates of development and interactions between two species of Chrysomya (Diptera: Calliphoridae) in laboratory culture. AB - Rearing of Chrysomya megacephala (F.) and Chrysomya rufifacies (Macquart) in pure cultures at seven different population densities (larvae per gram of liver) demonstrated an inverse relationship between density and the duration of the larval stage. In pure cultures, larval mortality rates decreased with increasing density until an optimum density was reached (8 larvae/g liver for C. megacephala and 10 larvae/g liver for C. rufifacies), then decreased directly with density. Puparial and adult weights varied inversely with density for both species in pure cultures. Internal feeding mass temperatures were above ambient temperatures for all cultures, with maximum temperatures recorded in cultures with 20 and 40 larvae/g liver for G. rufifacies and C. megacephala, respectively. In paired encounters, larvae of C. rufifacies were cannibalistic and predatory on C. megacephala larvae after the first instar. In mixed cultures of these two species, the larval mortality of C. rufifacies remained relatively stable, whereas the larval mortality of C. megacephala increased directly with population density. PMID- 2332877 TI - Feeding and host preference of immature Ixodes dammini, I. scapularis, and I. pacificus (Acari: Ixodidae). AB - A comparative study of feeding and host preference was made among immatures of Ixodes dammini Spielman, Clifford, Piesman & Corwin, I. scapularis Say, and I. pacificus Cooley & Kohls, using white laboratory mice, Eumeces lizards, and chickens (3-4 d old) as hosts. Larval feeding of each species when placed on hosts was greater (P less than 0.05) on mice than on chickens and lizards and higher on lizards than on chickens (P less than 0.05). When larvae of the three species were given a choice between mouse and lizard and mouse and chicken, they preferred mice (except no statistical difference was found between mice and chickens for I. pacificus larvae). When given a choice between lizard and chicken, no significant difference in host preference was seen. Nymphs of I. dammini, I. scapularis, and I. pacificus displayed no statistical difference in feeding ability between mice and lizards when placed on these hosts, but more ticks fed on mice and lizards than on chickens. Nymphs of all three species also showed no preference between mice and lizards but preferred either of these hosts to chickens (however, no statistical difference was found between mice and chickens for I. dammini nymphs or between lizards and chickens for I. pacificus nymphs). PMID- 2332879 TI - Localization of antigens and allergens in thin sections of the house dust mite, Dermatophagoides pteronyssinus (Acari: Pyroglyphidae). AB - Cryostat sections of the house dust mite, Dermatophagoides pteronyssinus, were probed in fluorescent microscopy studies with rabbit polyclonal and mouse monoclonal antibodies specific for mite allergens including the major allergen, Der p I. Sections also were probed for allergens with sera from human mite allergic subjects containing IgE antibodies to mite allergens and with lectins. Antibody binding was mainly to the gut lining and gut contents of the mite, although some specific labeling also was associated with the head region and cuticle. This is the first detailed localization of mite allergens in situ. The morphology of the mite was investigated using plastic embedded thin sections and was found to be similar to that previously described for D. farinae. PMID- 2332880 TI - Subadult Ixodes ricinus (Acari: Ixodidae) on rodents in Berlin, West Germany. AB - To identify hosts that may serve as reservoirs for the agent of Lyme disease in Central Europe, we determined whether Ixodes ricinus L. feed most frequently on certain rodents and whether the abundance of these hosts corresponds to the season of feeding activity of the tick in four sites in Berlin, Federal Republic of Germany. In addition, we correlated abundance of I. ricinus with that of particular rodent hosts. Two small rodents were more abundant than any others; a mouse, Apodemus flavicollis, predominated in a wooded site and a vole, Clethrionomys glareolus, in three brush- or grass-covered sites. The tick was most abundant in the mouse-infested site. Although A. flavicollis comprised only about a third of rodents collected, nearly 60% of all such rodent parasitizing I. ricinus fed on this mouse. These ticks were more abundant on mice than voles in each of the study sites and throughout the year, and more larvae fed on these rodents than did nymphs. Although larval as well as nymphal I. ricinus are most abundant during midsummer, they feed on rodents from April through October. Taken together, these observations suggest A. flavicollis as a potentially important reservoir host for I. ricinus-borne infections. PMID- 2332881 TI - Taxonomic relationships of the subgenus Rhipistoma (Acari: Ixodidae: Haemaphysalis). AB - The possible evolution of the haemaphysalid subgenus Rhipistoma (Koch) (Acari: Ixodidae, Haemaphysalis) is postulated. H. hispanica and H. caucasica seem to be the most primitive species of the subgenus, closely related to a common ancestor, as can be deduced from the palpal outline and from the combination of spines and spurs on the coxae and palpi. However, H. adleri, H. asiatica, H. fossae, H. eupleres, and H. obtusa compose a group of phylogenetically more-advanced species, based on the development of complex palpal structures in the adults, but which have also retained some of the more primitive characteristics in the immature stages. An evolutionary line containing many species seems to have developed from the subgroup H. hispanica (bequaerti, cooleyi, hyracophila, calcarata, and houyi), as inferred from the morphological features of the palpi. The data from lemuris suggest a distant relationship with the H. asiatica group. H. bartelsi and H. koningsbergeri seem to have evolved from a common ancestor of the subgenus (or even from the subgroup hispanica) because they share primitive morphological characteristics. Also, H. heinrichi and H. indica may be considered as two modern members within the indica subgroup, from which H. canestrinii seems to have originated. The data from the canestrinii group suggest the existence of a relationship between the indica-heinrichi-canestrinii subgroup, spinulosa subgroup and leachi subgroup, because they share many morphological features. H. bartelsi and H. koningsbergeri would remain as two species of a primitive pathway from the common ancestor of the subgenus, evolving to the canestrinii subgroup. H. erinacei and its subspecies form a group with several primitive features, linking it to the subgenus Ornithophysalis. Also, H. pedetes and H. zumpti are two very similar species that appear to have evolved from an arinacei-like ancestor. It seems possible that the leachi and spinulosa subgroups have evolved from a complex of species included today in the spinulosa and canestrinii subgroups. PMID- 2332882 TI - Susceptibility of Anopheles quadrimaculatus (Diptera: Culicidae) to subperiodic Brugia malayi and Brugia pahangi (Nematoda: Filarioidea) adapted to nude mice and jirds. AB - Anopheles quadrimaculatus and Aedes aegypti (Black-eyed Liverpool strain) were fed on jirds and nude mice (jird-jird infection, jird-mouse infection, and mouse jird infection) infected with subperiodic Brugia malayi and B. pahangi. Microfilariae of B. malayi from jird-mouse and mouse-jird infections developed normally in An. quadrimaculatus, whereas those from jird-jird infections did not develop. Microfilariae of both species from jirds and nude mice developed normally in Ae. aegypti and those of B. pahangi developed normally in An. quadrimaculatus. It is suggested that microfilariae from nude mice are modified physiologically, immunologically, or both so that they can develop in refractory An. quadrimaculatus, thus indicating that susceptibility and refractoriness of An. quadrimaculatus to B. malayi also is influenced by factors relating to the vertebrate host in addition to mosquito genetic factors. PMID- 2332883 TI - Morphogenesis of the brain as studied by 3-D computer graphics simulation. AB - Morphogenesis of the brain is analysed by 3-D computer graphics simulation. The initial form of the brain, i.e. a neural tube, is created in the computer as a small tubular figure in 3-D Cartesian coordinates which are subsequently transformed into curvilinear coordinates by a set of growth functions. By this method the morphological development of the human brain is simulated. The same computer program can be applied to simulate the development of the brains of mouse, rat and monkey simply by changing the parameters slightly. The result of the analysis reveals that the smaller brains are produced by faster growth of the matrix cell population at the onset of development, coupled with faster rate of retardation of the growth during ontogeny. Thus, smaller brains in smaller animals are produced in a shorter period during their ontogeny. PMID- 2332884 TI - The total number of neurons in the human neocortex unbiasedly estimated using optical disectors. AB - An efficient method is presented for obtaining, in under 4 h, an unbiased estimate of the total number of neurons in the human neocortex, with a coefficient of error on the estimate of approximately 5%. The novel sampling scheme used in this study is unbiased and was designed so that only a small amount of neocortical grey matter had to be removed. Hence, the majority of the cerebral grey matter and all the internal grey matter was left intact for further resampling and analysis. Each cerebral hemisphere was subdivided into the four major neocortical regions, sliced coronally at 7-mm intervals and the volume of the neocortex determined using Cavalieri's principle. Uniform sampling of neocortex was performed in the hemisphere followed by regional subsampling with a varying sampling fraction being taken from each region. Neuronal density estimates were made in thick plastic sections using optical disectors. Shrinkage estimates were made in parallel with the number estimates and found to be negligible. The total number of neocortical neurons in the right hemisphere of five normal 80-year-old men was found to be 13.7 x 10(9) with an inter-individual coefficient of variation of 12%. PMID- 2332885 TI - Image analysis of Nissl-stained neuronal perikarya in the primary visual cortex of the rat: automatic detection and segmentation of neuronal profiles with nuclei and nucleoli. AB - An image analysing procedure for the morphometric characterization of cortical neurons in Nissl-stained brain sections is described. It consists of the automatic detection of cellular profiles and their compartments: cytoplasm, nucleus and nucleolus. The algorithm was designed to cope with the large morphological spectrum of cortical perikarya (e.g. geometrical properties of perikarya, staining intensities of cell compartments and nucleo-plasmic area ratio) including pyramidal (Golgi-category I) and non-pyramidal (Golgi-category II) neurons. Clusters of cells were separated and non-neuronal structures (e.g. glia, endothelial cells) as well as tangential, non-nucleolated sections through neuronal perikarya recognized and excluded from further analysis without requiring interactive procedures. The performance of the profile recognition procedure was evaluated using 426 nucleolated and non-nucleolated profiles of different types of neurons in the primary visual cortex of the rat. Nucleolated profiles were recognized as such with a 91% accuracy, non-nucleolated profiles were rejected correctly in 90% of cases. After automatic segmentation and selection of nucleolated neuronal profiles from the microscopic field, a large set of quantitative morphological features including geometrical, densitometrical and textural parameters can be measured using high power light microscopy. This permits quantitative morphometric characterization of different neuronal types. This procedure is the first part of a system for the automatic classification of Nissl-stained cortical neurons. PMID- 2332886 TI - A quantitative approach to cytoarchitectonics: analysis of structural inhomogeneities in nervous tissue using an image analyser. AB - Cytoarchitectonic investigations are based on the analysis of structural inhomogeneities in the neuronal composition of nervous tissue. Boundaries of brain regions are established at locations where local structural properties, such as density, shape, orientation or arrangement of the nerve cells, change. A quantitative approach requires a complete scanning of histological sections and the measurement of at least one of these properties using an automatic device. In contrast to recently developed stereological methods which result in unbiased estimates of parameters and which are based on efficient sampling procedures, measurements with automatic devices are biased due to section thickness and problems in the segmentation of nerve cell bodies. Automatic measurements are necessary, however, if a complete scanning of histological sections is required in order to localize areal or laminar boundaries. In this approach, the grey level index (GLI) is measured with a TV-based image analysing system from routine histological sections. Using Nissl-staining, this parameter is a biased estimate of the local volume density of Nissl-positive structures (cell bodies). The histological section is digitized into a GLI image by a scanning procedure. The GLI image is processed by image enhancement procedures in order to visualize the laminar pattern. Areal boundaries are localized at positions where this laminar pattern changes. GLI statistics of single brain regions can easily be evaluated by delineating these regions with a cursor in the GLI images of the sections. Information from a series of sections is compiled by specific application programs. PMID- 2332887 TI - Renal transplantation in Mississippi. AB - The present article reviews the results of cadaveric renal transplantation and organ donation in Mississippi during the years 1984-88. Patient and graft survival in cadaveric renal transplantation have continued to improve since the introduction of cyclosporine as an immunosuppressive agent. In the Mississippi Transplant Program recipients of primary cadaveric renal transplants currently demonstrate 93% patient and 82.3% graft survival rates. Despite this improvement in outcome slightly more than 1% of ESRD patients in the state undergo transplantation annually compared to 7.5% nationally. PMID- 2332889 TI - Electrophysiologic recording as an aid in the clinical evaluation of "muscle jerks". PMID- 2332888 TI - A scheme for the treatment of hyperlipidemia. PMID- 2332890 TI - Report of activities, fiscal year 1989: Medical Licensure Board. PMID- 2332891 TI - The physician-patient privilege: the practical necessity of a written patient waiver. AB - Communications between physician and patient have been protected from disclosure to third parties with the enactment of state statutes. The medical privilege, as it is commonly known, now embodied in Rule 503 of the Mississippi Rules of Evidence, contains the limiting language that the privilege is waived only to the extent that the patient places his medical condition at issue in a judicial proceeding. The authors note that this oftentimes forces the physician to make difficult decisions concerning what information, if any, is to be disclosed to an outsider to the physician-patient relationship. It is therefore prudent for the physician to insist upon a carefully worded written authorization, executed by the patient, prefatory to release of any such information. PMID- 2332892 TI - Prisoner who opposes AIDS testing loses suit. PMID- 2332893 TI - Polymerase chain reaction and analysis of cancer cell markers. PMID- 2332894 TI - What's going on with research project grant funding at NCI? PMID- 2332895 TI - Researchers deal with funding frustrations. PMID- 2332896 TI - A chat with Trapeznikov, Russia's cancer czar. Interview by Eleanor Nealon. PMID- 2332897 TI - Pesticide exposure in grain industry raises cancer rates. PMID- 2332898 TI - Synergy recurrent theme of cancer therapy. PMID- 2332899 TI - Consensus developed for colon/rectal cancer. PMID- 2332900 TI - Cancer groups, dermatologists push for 'library look'. PMID- 2332901 TI - Measurement of progress against cancer. Extramural Committee to Assess Measures of Progress Against Cancer. AB - The questions of the extent of progress against cancer and how to measure it have stimulated attention among scientists and in Congress. In this presentation, we summarize a report requested by the Senate Appropriations Committee to address the adequacy of the existing measures of progress against cancer. The report was prepared by an extramural committee convened by the National Cancer Institute at the request of Congress. It includes extensive findings and recommendations on the existing measures of progress against cancer, the systems used to develop the data reported through the measures, the frequency and content of reports addressing progress, and the need for analytic research on this topic. Although the Extramural Committee To Assess Measures of Progress Against Cancer found the measures and systems to be generally adequate, they also found that modification or expansion of the information base is needed in many areas. PMID- 2332902 TI - Cancer mortality in the U.S. flour industry. AB - The mortality experience among 22,938 white males who were enrolled in the life insurance program of the American Federation of Grain Millers was assessed for the period 1955 through 1985 in a cohort mortality analysis and in a nested case control analysis. Significantly fewer deaths were observed among this group than expected for all causes of death combined [standardized mortality ratio (SMR) = 89] compared with the number of deaths observed among the general population of U.S. white males of the same age. Excess risks for developing non-Hodgkin's lymphoma (NHL) (SMR = 149), leukemia (SMR = 136), and pancreatic cancer (SMR = 133) were restricted to workers employed in flour mills, where pesticides are used more frequently than in other segments of the industry. In the nested case control analysis, excess risks for developing these cancers were also observed in these workers, but the relative risk for developing NHL [odds ratio (OR) = 4.2] was approximately twice that for developing pancreatic cancer (OR = 2.2) and that for developing leukemia (OR = 1.8). Within the flour mills, the workers who had ever worked in the maintenance department (OR = 8.1) or in the elevator department (OR = 2.8) were at particularly elevated risk of developing NHL, suggesting that exposures in these departments should receive further attention. PMID- 2332903 TI - Sensitive detection of estrogen receptor RNA by polymerase chain reaction assay. AB - We developed a simplified polymerase chain reaction (PCR) technique sensitive enough to detect estrogen receptor (ER) mRNA in breast tumor specimens from 1 microgram of total RNA. We simultaneously amplified a control gene such as beta actin as a baseline to semiquantitate ER expression. In a preliminary test of this method on a small series of breast tumors, ER message was found as expected in a number of tumors found to be ER positive by ligand binding assay, but also ER negative in one tumor assayed. The ER in this last tumor contained a single base change in the hormone binding region, compared with the MCF-7 breast tumor cell line ER. Therefore, this PCR technique may be useful in the detection and cloning of rare ER transcripts from breast tumor biopsy specimens. PMID- 2332904 TI - Serum selenium and subsequent risk of cancer among Finnish men and women. AB - The association between the serum selenium level and the subsequent incidence of cancer was investigated in a longitudinal study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. The baseline examinations, including the collection of blood samples, were performed in 1968-1972. During a median follow up of 10 years, 1,096 new cancer cases were identified from the files of the Finnish Cancer Registry. Selenium concentrations were measured from the stored serum samples collected from these cancer cases and from two controls per case, matched for sex, municipality, and age. The mean serum selenium level was 59.1 micrograms/L among all male cancer cases and 62.5 micrograms/L among controls. The difference was statistically significant (P less than .001). Corresponding values among women were 63.6 and 63.9 micrograms/L, respectively. Low serum selenium levels were associated with an increased risk of developing cancer at several sites, especially cancers of the stomach and lung among men. The relative risk of lung cancer between the highest and lowest decile of serum selenium was 0.11, and it differed significantly from unity (P less than .001). These findings are in agreement with the hypothesis that low selenium intake may increase the risk of some cancers among men. PMID- 2332906 TI - Cholesterol: the alarm and fear. PMID- 2332905 TI - Projecting breast cancer probabilities. PMID- 2332907 TI - AIDS among blacks in the 1990s. AB - In the black community, many health indicators are going in the wrong direction. Black life expectancy is going down. Our middle class is growing but our poor are growing also. It is no longer even jarring to talk about black males as an endangered species. Black women are groaning under family responsibilities. Too many of our young people are better armed than the police and kill each other for "diss'in," ie, he was disrespecting me. It is appropriate that AIDS be responded to as a crisis, but we also have a weighty, preexisting set of long-standing and equally lethal health and social ills. The infrastructure we build in response to AIDS and the lessons we learn from this disease must be developed with this broader view in mind. PMID- 2332908 TI - Comments from the National Medical Association concerning a "white paper" on proposed strategies for fulfilling primary care manpower needs. AB - The NMA has long had the participation and leadership of those in primary care and those who practice in medically underserved or medically indigent areas. We, therefore, are most supportive of the objectives and goals you have presented. We have offered suggestions to strengthen your "White Paper" by emphasizing the vital nature of the current and future role of primary health care delivery; by stating the effects that changes in physician reimbursement, especially utilizing the Relative Value Scale, will have on the expectations of those who are considering primary care; by continuing to offer scholarship assistance and loan forgiveness to those who are willing to commit during their medical education to a primary care career through the NHSC; by making a priority the effort to recruit older physicians by providing well-defined incentives, including liability relief; and by emphasizing the continued recruitment, retention, and encouragement of minority and disadvantaged applicants entering health care careers and stressing the support they must receive to be able to afford to practice in underserved areas. The National Medical Association welcomes the chance to undertake any collaborative efforts which may aid our mutual missions. Therefore, we are willing to assist you in helping to solve the critical need for primary care physicians in medically underserved communities. PMID- 2332909 TI - Correlation of waist to hips ratio to the prevalence of diabetes and hypertension in black females. AB - Regional fat distribution is an important risk factor for the development of diabetes and hypertension in white females; those with fat cells in the upper part of the body have a higher prevalence of diabetes and hypertension than those with similar degrees of obesity in the lower parts of the body. Whether this observation is relevant for the general population of black females is not known. In this article, we report the results of a study of fat distribution in black females and its correlation with the prevalence of diabetes and hypertension. One hundred black females who attend the Charity Hospital System of Louisiana were studied. Anthropometric measurements were taken, and the prevalence of both diabetes and hypertension determined by review of the medical record and patient interview. In this study, the waist to hips ratio was the index of fat distribution. Waist to hips ratio was found to increase with age. The observed prevalence of diabetes, hypertension, and both together was higher in those with upper body obesity: 40% of those in the lower quartile had diabetes, whereas 80% of those in the highest quartile had diabetes. The mean waist to hips of diabetic patients (0.95) was higher than the ratio for nondiabetics (0.90). Hypertensives also had a higher ratio (0.95) than nonhypertensives (0.89). This is the first study to show that waist to hips ratio in blacks correlates with the prevalence of diabetes and hypertension. This suggests that the measurement of waist to hips ratio is an important part of the physical evaluation and may be a predictor of morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332910 TI - Length of hospital stay in veteran surgical service patients with nosocomial infections. AB - Four hundred ninety-nine nosocomial infections (with 657 isolates) in 288 Surgical Service patients were monitored from February 1986 to June 1987 (17 months) to determine the influence that pathogen or site of infection had on the length of hospital stay. Patients with upper respiratory and skin infections were more likely to have significantly longer length of stay than those with infections in other sites. Infections with Haemophilus influenzae and Pseudomonas aeruginosa were more likely to yield longer culture to discharge periods than other organisms in certain settings. Extended lengths of stay were common in patients with nosocomial infections. PMID- 2332911 TI - AIDS: knowledge and attitudes among different ethnic groups. AB - To study the ethnic differences in knowledge, attitudes, and beliefs about AIDS, we surveyed 161 US residents from 31 different countries. An anonymous self administered questionnaire was developed to compile these data. The results of this survey suggest that AIDS-related knowledge is generally incomplete and there are still misconceptions about AIDS regardless of ethnicity or national origin. However, Americans and Europeans were more aware of some of the modes of contracting AIDS than were people from Asia, the Middle East, or Africa. We conclude that some ethnic and national groups are more likely to have misconceptions about AIDS than others. Therefore, additional public educational programs and activities with special outreach programs for ethnic groups in the United States must be accomplished through methods that are culturally sensitive if they are to be effective. PMID- 2332913 TI - AMA-RPS representatives testify on student loan deductibility. PMID- 2332912 TI - Sudden death in rheumatoid arthritis from vertical subluxation of the odontoid process. AB - Rheumatoid arthritis is a chronic, multisystem disease that causes significant morbidity and early mortality. A common source of morbidity in severe rheumatoid arthritis is involvement of the cervical spine. Sudden death due to subluxation of the odontoid process into the medulla oblongata is a dramatic but rare complication. We report the case of a patient who died suddenly. Computerized tomography scan, autopsy, and clinical findings were correlated. Studies of cervical involvement in rheumatoid arthritis were analyzed for cases of vertical subluxation. The case reports of sudden deaths and patients treated for vertical subluxation were reviewed; they revealed a trend toward surgery in patients with neurological abnormalities. However, a comparison of clinical outcome does not demonstrate improved survival with surgical intervention. Randomized trials comparing surgical with nonsurgical therapy are needed. PMID- 2332914 TI - Health management fellowships offered. PMID- 2332915 TI - Medium isn't accurate 'Ice Age' message. PMID- 2332916 TI - Vitamins during pregnancy and neural tube defects. PMID- 2332917 TI - Fluphenazine and postherpetic neuralgia. PMID- 2332918 TI - Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). AB - To determine the sensitivities and specificities of ventilation/perfusion lung scans for acute pulmonary embolism, a random sample of 933 of 1493 patients was studied prospectively. Nine hundred thirty-one underwent scintigraphy and 755 underwent pulmonary angiography; 251 (33%) of 755 demonstrated pulmonary embolism. Almost all patients with pulmonary embolism had abnormal scans of high, intermediate, or low probability, but so did most without pulmonary embolism (sensitivity, 98%; specificity, 10%). Of 116 patients with high-probability scans and definitive angiograms, 102 (88%) had pulmonary embolism, but only a minority with pulmonary embolism had high-probability scans (sensitivity, 41%; specificity, 97%). Of 322 with intermediate-probability scans and definitive angiograms, 105 (33%) had pulmonary embolism. Follow-up and angiography together suggest pulmonary embolism occurred among 12% of patients with low-probability scans. Clinical assessment combined with the ventilation/perfusion scan established the diagnosis or exclusion of pulmonary embolism only for a minority of patients--those with clear and concordant clinical and ventilation/perfusion scan findings. PMID- 2332919 TI - Exercise training combined with antihypertensive drug therapy. Effects on lipids, blood pressure, and left ventricular mass. AB - We studied exercise training combined with the use of antihypertensive drugs and examined the following questions. (1) Are there additive antihypertensive benefits with exercise and drug therapy combined? (2) Does drug therapy limit exercise-induced lipid improvements? (3) Does exercise that includes weight training and walking/jogging affect the left ventricle? Fifty-two hypertensive men were randomly assigned, double-blind, to diltiazem hydrochloride, sustained release (360 mg daily), propranolol hydrochloride (240 mg daily), or placebo and exercised three times per week for 10 weeks. Baseline blood pressure (145/97 mm Hg) fell after training (131/84 mm Hg) in all groups. Exercise decreased total and low-density lipoprotein cholesterol levels in all groups. Increases in the levels of high-density lipoprotein cholesterol were similar in placebo and diltiazem groups, whereas the propranolol group changed in an opposite direction. In all groups, left ventricular mass increased with training, while diastolic function was unchanged. We conclude that (1) drug therapy provided no additive benefit to the antihypertensive effects of exercise, (2) propranolol limited improvements in high-density lipoprotein cholesterol, and (3) exercise did not adversely affect the left ventricle. PMID- 2332920 TI - The 'incidentaloma' of the pituitary gland. Is neurosurgery required? AB - We describe a series of 18 patients with an intrasellar mass incidentally discovered by computed tomography or magnetic resonance imaging. The average size of the mass was 13 mm, with a range from 5 to 25 mm. Initial ophthalmologic examination revealed bitemporal hemianopia in 2 patients. Results of routine endocrine testing showed partial hypopituitarism in 5 patients and growth hormone hypersecretion without signs and symptoms of acromegaly in 1 patient. Four patients underwent neurosurgery. Histologically, one chondroid chordoma and three pituitary adenomas were found. In the remaining 14 patients treated conservatively, repeated computed tomography and magnetic resonance imaging revealed no significant change in tumor size at the time of follow-up (median, 22 months). Our results suggest that the "incidentaloma" of the pituitary gland is a benign condition that does not necessarily require neurosurgical intervention. PMID- 2332921 TI - The cystic fibrosis gene: medical and social implications for heterozygote detection. AB - The primary goal of mass screening programs for cystic fibrosis carriers should be to allow people to make more informed reproductive decisions. However, previous experience with genetic screening programs, including those for phenylketonuria and sickle cell disease, have revealed complex problems including error, confusion, and stigmatization. These problems could be greater with cystic fibrosis, since more than 8 million Americans may be carriers and entrepreneurial interests can be expected to promote screening in what could become a billion dollar industry. The present frequency of the detectable mutation (delta F508), 75%, will complicate the counseling process. The sensitivity of the test to detect at-risk couples would be 56%. The cost of screening could be as much as $2.2 million for each cystic fibrosis birth avoided. Regardless of improvements in the detection rate, implementation of population screening should be delayed until pilot studies that demonstrate its safety and effectiveness are completed. While studies are in progress, preconception testing should be offered to adult relatives of cystic fibrosis patients as part of a comprehensive program following institutional review board approval for "compassionate use." The purpose of such review should be to ensure that strict standards of informed consent, education, quality control of the testing procedure, and counseling are followed. Primary care physicians who are unable to offer screening as part of such a comprehensive program should refer high-risk patients who would like to consider being tested to established centers. PMID- 2332922 TI - Who profits from tobacco sales to children? AB - It is estimated that more than 3 million American children under 18 years of age consume 947 million packs of cigarettes and 26 million containers of smokeless tobacco yearly. These tobacco products account for annual sales of $1.26 billion. Approximately 3% of tobacco industry profits ($221 million in 1988) derive directly from the sale of cigarettes to children, an activity that is illegal in 43 states. Approximately half of the tobacco industry's profits, or $3.35 billion annually, derives from sales to people who became addicted to nicotine as children. Tax revenues to the federal ($152 million) and state ($173 million) governments from cigarette sales to children dwarf governmental expenditures on smoking and health. We describe how dozens of communities have effectively enforced laws that prohibit the distribution of tobacco to children and offer some suggestions for increasing efforts to prevent nicotine addiction. PMID- 2332923 TI - Conflicts of interest in medical center/industry research relationships. Council on Scientific Affairs and Council on Ethical and Judicial Affairs. PMID- 2332924 TI - Methods of smoking cessation--finally, some answers. PMID- 2332925 TI - A piece of my mind. Portraits. PMID- 2332926 TI - Clinicopathologic studies on various heart diseases--light and electron microscopic analysis of autopsied and biopsied human heart tissue specimens. PMID- 2332927 TI - Biatrial isolation--a new surgical treatment for supraventricular tachycardia. AB - Nine adult mongrel dogs were subjected to cardiopulmonary bypass and both right and left atria were surgically isolated, exclusive of the sinoatrial (SA) node, crista terminalis, and interatrial septum. Thus, the SA node remained in continuity with the ventricles despite biatrial isolation. Moreover, of the right and left SA node arteries, the predominant one (right in 7 dogs, left in 2 dogs) was spared. Postoperatively, normal SA node function was preserved in 8 out of 9 dogs, with no difference in sinus rhythm cycle length (preop: 446 +/- 25, postop: 434 +/- 22 sec, p = NS) or sinus node recovery time (preop: 488 +/- 28, postop: 487 +/- 32 msec, p = NS). Simulated supraventricular tachycardia was confined in the isolated right or left atria did not affect sinus rhythm in the remainder of the heart. One out of 9 dogs developed junctional rhythm postoperatively, indicating exclusion of the SA node or a fast atrial pacemaker. In the 8 dogs with postoperative sinus rhythm, the spared SA node artery was occluded at the end of each study. All dogs developed rhythm deterioration including sinus rhythm slowing with prolonged sinus node recovery time (4 dogs), sinus bradyarrhythmia (2 dogs) and atrioventricular nodal rhythm (2 dogs). Thus, biatrial isolation is feasible for the treatment of supraventricular tachycardia, but it is essential to preserve SA node blood supply in order to maintain normal sinus rhythm in the remainder of the heart. PMID- 2332929 TI - The role of late potentials in the assessment of myocardial degeneration in idiopathic dilated cardiomyopathy. AB - In order to determine whether or not late potentials indicate either a degree of myocardial fibrosis or necrosis, the relationship between late potentials and thallium-201 myocardial perfusion images was studied in 13 patients with idiopathic dilated cardiomyopathy. Late potentials were defined as low-amplitude waveforms having duration of over 20 msec after the end of the QRS complex using a high-resolution ECG (Marquette electronics, MAC 1). In the T1-201 myocardial perfusion image, the segmental perfusion state was assessed by use of a parameter called the uptake index (= normalized sector counts/maximal normalized sector counts) of each of 6 different segments. Segments which showed an uptake index of -2SD less than the normal value were judged to be abnormal. Late potentials were detected in 8 (61.5%) of the 13 patients. All of the patients showing late potentials also had ventricular tachycardia. Among the patients showing no late potential, ventricular tachycardia was observed in only one patient. Seven of the 8 patients showing late potentials and 3 of 5 patients not showing late potentials, however, had both a higher degree and a greater extent of abnormal perfusion images than the patients not showing late potentials. Therefore, late potentials may reflect a degree of myocardial fibrosis or necrosis in patients with dilated cardiomyopathy, those showing abnormal thallium images are apt to show late potentials, and these patients seem to be also at a high risk of suffering from ventricular tachycardia. PMID- 2332928 TI - The mechanism of protective effect of diltiazem on reperfusion-induced arrhythmias in isolated rat heart. AB - This investigation was undertaken to define the mechanism by which diltiazem protects against life-threatening, reperfusion-induced arrhythmias. Using an isolated retrogressively perfused rat heart preparation with transient coronary artery occlusion, we compared the effects of diltiazem in its active form (d-cis) to its stereo-isomer (1-cis). Pre-ischemic administration of d-diltiazem (5 x 10( 8), 5 x 10(-7), 5 x 10(-6) M) caused a dose-dependent reduction in ventricular arrhythmias upon reperfusion following 10 min of regional ischemia. The incidence of reperfusion-induced ventricular fibrillation (RVF) was 50%, 0% (p less than 0.05) and 0% (p less than 0.05) with 5 x 10(-8), 5 x 10(-7), 5 x 10(-6) M diltiazem, respectively, compared with 60% in the control group. Preischemic administration of the 1-isomer caused different dose-dependent reduction in RVF. With 5 x 10(-6) M, the 1-isomer also reduced the incidence of RVF to 0% (p less than 0.05). However below this concentration it was ineffective (67%). D diltiazem (5 x 10(-7) and 5 x 10(-6) M) increased coronary flow from 11.5 +/- 1.9 ml/min to 15.3 +/- 1.6 ml/min (p less than 0.05) and 15.2 +/- 1.0 ml/min (p less than 0.05) respectively, prior to ischemia. In contrast, the same dose of the 1 isomer did not alter coronary flow. The highest dose (5 x 10(-6) M) of d diltiazem decreased heart rate by approximately 30% during the reperfusion phase, but all other concentrations had no significant effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332930 TI - Characterization of slow conduction in the common type of atrial flutter--using transient entrainment. AB - To characterize slow conduction of the common type of atrial flutter (common AF), in which excitation wave propagated in a counterclockwise fashion, transient entrainment during the distal high lateral right atrium (HRAd) pacing and during the proximal coronary sinus (CSp) pacing was studied in 7 patients with common AF. In transient entrainment of common AF, conduction time from stimulus to CSp during HRAd pacing was always longer than that from stimulus to HRAd during CSp pacing. It was also longer than that from stimulus to CSp during HRAd pacing in 5 control patients without common AF in sinus rhythm. Return cycles at HRA and CS after cessation of rapid pacing during transient entrainment were studied. In HRAd pacing, return cycle at the proximal high lateral right atrium was almost equal to the pacing cycle length, or almost equal to or slightly shorter than the flutter cycle length (AFCL). Return cycle at CSp was almost equal to AFCL. In CSp pacing, return cycle at the distal coronary sinus was much longer than AFCL and increased at progressively shorter pacing cycle lengths. In conclusion, slow conduction was demonstrated in the lateral limb (from HRA laterally to CS) of the reentrant circuit in common AF, but it did not exhibit decremental conduction property. Return cycle at an endocardial recording site after transient entrainment in common AF does not always exhibit an uniform pattern, affected by the relative location of and the distance between the recording site, the pacing site, the reentrant circuit and the area of slow conduction. PMID- 2332931 TI - Computerized M-mode echocardiographic assessment of left ventricular diastolic function in patients with familial amyloid polyneuropathy. AB - To determine left ventricular diastolic properties in patients with familial amyloid polyneuropathy, 23 patients were studied by digitized M-mode echocardiography and were compared with 15 age-matched normal subjects. None of the patients had restrictive ventricular physiology and all but two showed normal left ventricular fractional shortening. Both the normalized peak rate of diastolic increase in left ventricular internal dimension and the normalized peak rate of diastolic thinning of posterior wall were significantly lower in patients than in normal subjects (2.0 +/- 0.8 vs 3.0 +/- 0.4 sec-1; p less than 0.001, and 2.5 +/- 1.2 vs 5.8 +/- 1.0 sec-1; p less than 0.001, respectively). The left ventricular isovolumic relaxation time in patients was 91.5 +/- 22.2 msec, compared with 64.0 +/- 2.6 msec in normal subjects (p less than 0.001). Of the 18 patients without clinical evidence of overt heart disease, 12 had normal ventricular wall thickness and normal fractional shortening, but 10 of the 12 exhibited some abnormalities in diastolic properties. In addition, indexes of diastolic function were significantly related to ventricular wall thickness alone. These findings indicate that left ventricular diastolic abnormalities precede the development of clinically overt heart disease, ventricular wall thickening, and systolic dysfunction and may be related to intramyocardial amyloid infiltration with resultant fibrosis in patients with familial amyloid polyneuropathy. PMID- 2332932 TI - Restenosis after percutaneous transluminal coronary angioplasty--a histopathological study using autopsied hearts. AB - Restenosis was studied histopathologically by serial step sectioning of 22 coronary arteries from 21 patients in whom percutaneous transluminal coronary angioplasty (PTCA) had been performed (9 arteries from patients who had died shortly after PTCA and 13 from those who had died considerably later). Nine of the 13 arteries from the patients who had died long after PTCA were immunohistochemically stained using anti-actin antibody for examination of spindle-shaped cells proliferating in the intima. In the patients who had died shortly after PTCA, all 9 arteries showed fresh thrombus formation. In the patients who had died considerably later after PTCA, however, there was fragmentation of the internal elastic lamina (IEL) in 9 arteries. In each of these 9 arteries, a remarkable proliferation of intimal cells was observed on the intimal side, mainly at the site of the IEL fragmentation. These spindle-shaped cells were identified as smooth muscle cells (SMC) because they stained reddish brown with Masson's trichrome, and because immunohistochemical staining with anti actin antibody was also positive. In 2 arteries, proliferation of SMC and elastic fibers was observed on the luminal side of the intima, despite absence of fragmentation in the IEL. Proliferation of SMC in false lumens was identified in 2 patients with medial dissection. From the above findings, the following 4 forms of restenosis after PTCA have been identified: 1. thrombus formation; 2. proliferation of SMC on the intimal side, mainly around fragmentation in the IEL; 3. proliferation of SMC on the luminal side of the intima where there was no fragmentation of the IEL; and 4. proliferation of SMC in dissected false lumen. The proliferation of SMC on the intimal side of the disrupted IEL was thought to have been a result of migration of SMC from the media to the intima, because SMC proliferation was seen around the disrupted region. PMID- 2332933 TI - Long-term prognosis of patients with congestive heart failure. AB - Factors determining prognosis in 100 patients with recent onset of congestive heart failure (CHF) were evaluated. The 1 year, 3 year, 5 year, and 10 year survival rates in the entire CHF group were 78.5%, 59.8%, 50.4% and 14.7%, respectively. No correlations between age, sex, heart rate and cardiothoracic ratio, and the cumulative survival rate were found. The prognosis of patients with CHF due to underlying coronary artery disease or primary cardiomyopathy was poor compared with that of patients with other types of heart disease. Patients whose NYHA classification was class III or VI had a significantly lower survival rate than those in class II. Patients with lower left ventricular stroke work and consecutive ventricular premature depolarization also had a significantly lower survival rate. These results suggest that functional status, underlying heart disease, left ventricular stroke work, and the presence of ventricular tachycardia provide important information regarding the long-term prognosis in patients with congestive heart failure. PMID- 2332934 TI - Clinical and exercise echocardiographic findings in patients with mitral valve prolapse. AB - To assess the relationship between left ventricular functional reserve and prognosis in patients with idiopathic mitral valve prolapse, ergometer exercise echocardiography was performed in 10 normal subjects and 30 patients with mitral valve prolapse having either mild, or no mitral regurgitation. These 30 patients with mitral prolapse were followed for 2 to 8 (mean 4.5) years. Increment of % fractional shortening during maximum exercise at the initial study in patients with mitral valve prolapse and normal subjects were 7 +/- 7 and 11 +/- 3%, respectively. Based on increment of % fractional shortening, patients with mitral valve prolapse were divided into 2 groups; Group I: 13 cases with delta% fractional shortening less than 5%, Group II: 17 cases with delta% fractional shortening greater than or equal to 5%. The incidence of cardiac symptoms was higher in Group I than in Group II (85 vs 41%, p less than 0.05). ST-T changes and life-threatening arrhythmias were more frequently observed in Group I. During the follow-up period, M-mode echocardiographic measurements did not vary in Group II, but left ventricular and left atrial dimensions increased significantly (p less than 0.05, p less than 0.01, respectively) and % fractional shortening decreased significantly (p less than 0.01) in Group I without any change in mitral regurgitation severity. Thus, some patients with mitral valve prolapse not having significant mitral regurgitation may develop progressive deterioration of the cardiac function, which may be predicted by exercise echocardiography. PMID- 2332935 TI - Adenylate cyclase activities of vascular smooth muscle in early and established DOCA/salt hypertensive rats. AB - It has been demonstrated that the adenylate cyclase activity of vascular smooth muscle regulates its tonus. The present study was undertaken to examine adenylate cyclase activity in early and established deoxycorticosterone acetate (DOCA)/salt hypertensive rats. Early and established DOCA/salt hypertensive rats were prepared by injecting 30 mg of DOCA weekly for 3 and 10 weeks, respectively, into male Wistar rats given drinking water with 1% saline. The membrane protein fraction medium containing the protein, 50 microM isoproterenol, 100 microM GTP, 50 microM forskolin or 25 microM calmodulin was applied. The adenylate cyclase activity was determined by a modified method developed in our laboratory using double isotope counting. The adenylate cyclase activity in the early DOCA/salt hypertensive rats was significantly higher (p less than 0.05) than that in the control rats in the basal condition, which was unaffected by additions of isoproterenol, GTP or forskolin. There was no significant difference in basal adenylate cyclase activity between the established DOCA/salt hypertensive and control rats. The adenylate cyclase activities in the established DOCA/salt hypertensive rats were significantly lower with GTP (p less than 0.02) and forskolin (p less than 0.01) as compared with the control rats. Calmodulin elevated the adenylate cyclase activity significantly (p less than 0.05) in the established DOCA/salt hypertensive rats as well as in the control rats. However, enzyme activity with calmodulin in the established DOCA/salt hypertensive rats was significantly lower (p less than 0.05) than that in the control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2332936 TI - Central inhibition of gastric motility by intravenously administered nicotine in rats. AB - Effects of intravenously (i.v.) administered nicotine on gastric motility were investigated in urethane-anesthetized rats in which an intragastric balloon had been placed. I.v. administered nicotine at 75-300 nmole/kg dose-dependently decreased gastric motility. Decrease in gastric motility induced by nicotine at the dose of 300 nmole/kg was inhibited by intracisternally administered hexamethonium. Gastric motility was also decreased by intracisternally applied nicotine (1-10 nmole). These doses were much smaller than those by the intracerebroventricular route in our previous report. Bilateral vagotomy significantly suppressed basal gastric motility. In bilaterally vagotomized animals, nicotine at 1 mumole/kg but not 300 nmole/kg given i.v. significantly decreased the gastric motility maintained at a normal level by electrical stimulation of the vagus nerve. This nicotine-induced decrease in gastric motility, under conditions of electrical stimulation of the vagus nerve, was inhibited by pretreatment with phentolamine. These results suggest that a smaller dose of nicotine given i.v. activates nicotinic receptors in the brainstem and elicits vagally-mediated inhibition of gastric motility. Activation of peripheral alpha-adrenergic mechanisms together with that of central nicotinic mechanisms may be involved in the decreasing effects of a larger dose of nicotine on gastric motility. PMID- 2332937 TI - Effects of various drugs on bladder function in conscious restrained-denervated rats placed in a restraining cage and produced by transection of the hypogastric nerve. AB - We evaluated the effects of various intravenously administered drugs, which had been shown to influence bladder function in anesthetized and/or conscious rats, on the cystometrogram in conscious restrained-denervated rats (produced by transection of the hypogastric nerve) placed in a restraining cage in comparison to those in conscious restrained-intact rats (with the hypogastric nerve intact) placed in a restraining cage. The bladder capacity in the restrained-denervated rats was smaller than that in restrained-intact rats and did not change when they were transferred to a wide cage, but the bladder capacity of the restrained intact rats decreased following transfer to the wide cage. Therefore, the activity of the hypogastric nerve in conscious rats appears to be stimulated by restraint. Atropine suppressed the amplitude of the micturition contraction (time to micturition in the cystometrogram). In the restrained-denervated rats, thiopental and indomethacin increased the bladder capacity at almost the same doses as those in restrained-intact rats, but it took a higher dose of morphine to increase the bladder capacity than in restrained-intact rats. These findings suggest that cystometrography in restrained-denervated rats is a useful method for evaluating the effect of a newly developed agent on bladder function without any influence from the hypogastric nerve. PMID- 2332938 TI - Relationship between running activity rhythm and the development of activity stress ulcer in rats. AB - In the present study, the relationship between the development of activity-stress (A-S) ulcer and the behavioral and physical changes of rats with the A-S paradigm was investigated. We applied the endoscopic technique to establish the A-S ulcer as a model for studying the therapeutic or healing process of ulcers. Male and female rats were subjected to daily 1 hr feeding in the light (L)-phase (09:00 10:00) or in the dark (D)-phase (21:00-22:00). Prior to peak-revolution of running-activity, ulcer occurred earlier in the L-phase feeding group than in the D-phase feeding group. The ulcer development was accompanied with a change in the circadian rhythm of running-activity; e.g., the running-activity of the L-phase was higher than that of the D-phase. This phenomenon was more marked in the L phase feeding group than in the D-phase feeding group. In addition, the ulcer development was closely related to body weight loss. No sex differences were found in these phenomena. The results suggest that change in the circadian rhythm of running-activity, body weight loss and high running-activity are important variables for predicting the A-S ulcer production, avoiding the need to kill the animals to determine ulcer formation. PMID- 2332939 TI - Effects of calcium channel blockers and hydralazine on plasma glucose levels in streptozotocin-induced diabetic rats in vivo. AB - Effects of calcium channel blockers from structurally different classes and hydralazine on plasma glucose levels were examined in streptozotocin-induced diabetic rats in vivo. Non-dihydropyridine calcium channel blockers (verapamil, diltiazem, 1.0-10 mg/kg, i.p.) did not significantly affect the basal plasma glucose level, and dihydropyridine calcium channel blockers (nifedipine, 0.1-0.3 mg/kg, i.p,; nicardipine, 0.35-0.70 mg/kg, i.p.) caused mild hyperglycemia, which was blocked by the administration of the beta-adrenoceptor antagonist propranolol. In contrast, hydralazine markedly produced hyperglycemia, which was also inhibited by the combined administration of propranolol. The selective alpha 1-adrenoceptor antagonist prazosin greatly potentiated the hydralazine-induced hyperglycemia. Isoproterenol alone showed hyperglycemia similar to that of hydralazine. Hexamethonium (40 mg/kg, i.p.), a ganglionic blocker, blocked the hydralazine-induced hyperglycemia. There was a negative correlation between the hyperglycemic effect and the blood pressure lowering effect by different doses of hydralazine in streptozotocin-diabetic rats, but not in normal rats. These results suggest that endogenous catecholamines are involved in the hydralazine induced hyperglycemia through the interaction with beta-adrenoceptors in streptozotocin-diabetic rats in vivo. PMID- 2332940 TI - Effects of the calmodulin antagonist W-7 on isometric tension development and myosin light chain phosphorylation in bovine tracheal smooth muscle. AB - Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on isometric tension development and myosin light chain (P-LC) phosphorylation were determined in intact smooth muscle strips of bovine trachea. Addition of 10(-5) M carbachol resulted in a marked increase in the P-LC phosphorylation within 30 sec of stimulation. Subsequently, there was a gradual decrease in the P-LC phosphorylation. In contrast, steady-state contraction was not attained until 10 min of stimulation. In these strips, W-7 itself caused a contraction, probably due to the release of endogenous histamine that was blocked by pyrilamine. In the presence of W-7 and pyrilamine, the isometric tension development and P-LC phosphorylation during the initial 5-min stimulation period were inhibited. Concentrations of W-7 that caused a 50% inhibition were 145 and 125 microM, respectively, for tension and phosphorylation. N-(6-aminohexyl)-1 naphthalenesulfonamide (W-5), a weak calmodulin antagonist, produced no significant inhibition on the carbachol-induced isometric tension development and P-LC phosphorylation. After 10-min exposure to carbachol, W-7 inhibited the steady-state contraction without inhibition of the P-LC phosphorylation. These results suggest that 1) W-7 inhibits the smooth muscle contraction through the inhibition of the initial increase in the P-LC phosphorylation and 2) the maintenance of isometric tension (after 10 min exposure to carbachol) in unlikely to depend on the P-LC phosphorylation. PMID- 2332941 TI - Pharmacological activity of angiotensin-II modified by tyrosine sulfation. AB - An angiotensin-II analogue with a sulfated tyrosine residue was prepared by arylsulfotransferase treatment of synthetic human angiotensin-II. Its biological activities were studied in isolated smooth muscles, and its effect on blood pressure was determined. The sulfated angiotensin-II (AII-S) was about 15-30 fold less potent than angiotensin-II (AII) for ileum contraction and gallbladder contraction. The hypertensive potency of AII-S was about 30-fold less than that of AII. PMID- 2332942 TI - Influence of corticosterone on tracheal mucociliary transport in pigeons. AB - The effects of corticosteroids on tracheal mucociliary transport (MCT) were examined in pigeons. Intramuscular administration of corticosterone had no effect at 1.0 mg/kg, while at a larger dose of 5.0 mg/kg, it slightly, but significantly increased the MCT rate. Metyrapone significantly decreased the MCT rate, and the inhibitory action was blocked by 1.0 mg/kg corticosterone. The present study suggested that corticosteroids modulated the mucociliary clearance, especially under some diseases associated with a decreased level of endogenous corticosteroids. PMID- 2332943 TI - Assessment of vascular permeability increase in the mouse by dye leakage during paw edema. AB - Vascular permeability increase induced by histamine, bradykinin, platelet activating factor (PAF), or phorbol myristate acetate (PMA) in the mouse paw was assessed by the dye leakage method. The amount of dye extracted from the paw showed a clear dose-response relationship to the dose of each agonist injected into the paw. Among the autacoids used, PAF showed the most potent activity in the mouse paw. The results are consistent with those seen in the rat dorsal skin as previously reported. Involvement of histamine, 5-hydroxytryptamine and PAF is suggested in the vascular permeability increase induced by PMA in the mouse paw. PMID- 2332944 TI - [Development and organization of breast milk collection centers in East Germany]. AB - Human milk banking has a longstanding tradition in the GDR. We report on the main data of a survey carried out in 1987, actualized in 1989. Whereas human milk banking was widespread during the 1950s, it reached it's lowest level in 1972. In 1988 the amount of collected milk was nearly 200,000 litres (60 milk banks). Thus, the supply met the demand approximately. The development of the human milk banks is characterized by an increase of the number of milk banks (mostly the banks are affiliated to a children's hospital) and the collecting capacity. Half of the milk banks carries out the collection on a daily basis. This makes it possible to provide fresh milk with it's clear-cut advantages, especially in immunological respect. Otherwise the milk is stored after boiling, freezing or pasteurization. The feeding of very low birth weight newborns with fresh human milk is steadily increasing with corresponding consequences for the quality control of donated milk and the management of milk banks. PMID- 2332945 TI - [Clinical aspects, diagnosis and therapy of nesidioblastosis]. AB - Hyperinsulinemia due to an excessive secretion of insulin independent on normal regulation is the most frequent cause of persistent neonatal hypoglycemia. We report on clinical course, diagnostic procedures and treatment of nesidioblastosis in three patients. Main symptoms observed in newborn period were hypoglycemia, respiratory embarrassment, cyanosis and convulsions. Primary treatment was started by continuous infusion of glucose, administration of diazoxide and prednisolone or glucagon. Most important investigations were performed simultaneously. In all three children subtotal resection of pancreas was necessary, because there was no constant blood glucose level. Histological specimens confirmed diagnosis. In two of three patients pancreatectomy followed. One suffers from diabetes mellitus, the other one fed normally, has stable blood glucose level possibly due to existence of extrapancreatic insulin producing cells. PMID- 2332946 TI - [Diagnostic value of the early auditory evoked potentials in acute cranio cerebral trauma in children]. AB - The brainstem auditory evoked potentials were recorded in 54 children within the first 48 hours after a head trauma of different degree. In comparison with an age -appropriate standard group there are changed BAEP in 51% of the examined children after head trauma. The abnormalities mainly consist in changes of the wave--morphology, the latencies of the waves 1, 3 and 5 were significantly prolonged. The interpeak--intervals only unessentially differ from the standard group. The detected BAEP--changes are of different kind and incidence. A typical change of the potential for the infantile head trauma cannot be found. The regression of the traumatically conditioned BAEP--changes begins during the first days after trauma and it is finished within 6 months in half of the children. In the particular case changes can be detected after two years yet. PMID- 2332947 TI - [Initial experiences with "Oranienburg" slow-release theophylline in asthma therapy of children and adolescents]. AB - Experiences in 50 patients show that Theophyllin retard Oranienburg (280 mg theophylline) could be used as an effective bronchospasmolytic drug on conditions of mono- and combination-therapy. Advantages of this preparation are improvement of the compliance and an undisturbed night-sleep in patients. However an optimum dosage is hardly maintained in children by the present dose of a single tablet of 280 theophylline content. The effectiveness in therapy of childhood asthma could be improved by stronger sustained release effect and different doses of tablets. PMID- 2332949 TI - [Preventive and social pediatric activity at a university pediatric clinic. Retrospect--prospects]. AB - Changes and results of prophylactic and socialpediatric activities at a childrens hospital are represented. The advantages of cooperation between prophylactic and curative spheres are emphasized, they are useful for research and education of students. Decrees are prepared for arrangement of such departments in every university childrens hospital corresponding to the future pediatric development. PMID- 2332948 TI - [Malignant tumors of the lung and bronchi in children and adolescents. 2. Analysis of 66 cases of the East German National Cancer Registry (1961-1985)]. AB - In the National Cancer Registry of the GDR from 1961 to 1985 only 66 cases malignant (and semimalignant) tumors of the bronchi and lung in patients under 20 years of age were collected. These amounted to 0,037 per cent of all tumor cases of this localization. These tumors affected 37 boys and 29 girls. Tumors of mesenchymal origin prevailed (32 cases = 48.4 per cent) in comparison to those of epithelial (37.8 per cent) and embryonal origin (10.7 per cent). Among these cases were 10 bronchial carcinomas and 10 bronchial adenomas. 51.5 per cent of all patients died in the clinic. Less than half of the patients were due to adequate therapy discharged free of any tumor. Data about the late prognosis of these patients were not available. PMID- 2332950 TI - [Blood and serum iron values in children at child day care centers. 1]. AB - The parameters of iron in blood and in serum were studied with 90 children aged from 13 to 36 months from eight creches of a large city. The investigations were performed in state of health, in state of acute respiratory disease and until the fourth week of convalescence. In the acute state iron of serum, transferrine and saturation index of transferrine are situated outside the limits of the normal state. The initial values of the state of health were not reached yet in the fourth week of the convalescence. PMID- 2332951 TI - [Ptosis as the leading symptom of Kearns-Sayre syndrome. A case report for differential diagnosis of external ophthalmoplegia]. AB - Progressive external ophthalmoplegia has generally been considered a brainstem syndrome, but new investigative techniques have identified a variety of etiologies. We report a 17-year-old girl in whom Kearns-Sayre syndrome presented as unilateral ptosis with progression to bilateral ptosis, and discuss the clinical, biochemical, electrophysiological, histopathological and computerized tomographical findings. PMID- 2332952 TI - [Diagnosis of muscle function in hereditary muscular dystrophies]. AB - The evaluation of musclefunction im myopathies has been done upto now only by clinical trial. But in contrast in the field of medicine in sports has been proved the method of dynamometry of the muscles for a longer time which are necessary for objectivation of musclefunktion in myopathies. In this paper we present first results of health children and children suffering from Duchenne myopathy. PMID- 2332953 TI - [Public health in Switzerland. What specialists?]. PMID- 2332954 TI - [Health in 2000. Nursing education and Health for All in 2000 in Europe. What are our colleagues (in other countries) doing?]. PMID- 2332955 TI - [Primary health nursing and education programs. Current new dispositions]. PMID- 2332956 TI - [Politics for the future. Interview with Edna Chevalley by Francoise Taillens]. PMID- 2332957 TI - [Tomorrow's public health nurse: competent, versatile, bent on reform]. PMID- 2332958 TI - [Health education: prevention of doping in sports. Watch your muscles!]. PMID- 2332959 TI - [Alcoholism: what role for the nurse? Finding a new way]. PMID- 2332960 TI - [Birth of a Group of Common Interests. Nursing and computers]. PMID- 2332961 TI - [On my way with nurse Karin Dawes in the Zurich drug hell. "For many addicts I am a confidante"]. PMID- 2332962 TI - [Interview with Thorwald Dethlefsen on "nursing 2000" by Fred Arm. The "healthy person" is an illusion]. PMID- 2332963 TI - [Students learn to promote health]. PMID- 2332964 TI - [Nursing, where to? Exaggerated individualism--lacking professionalism]. PMID- 2332965 TI - ["Health for all" strategy in kantonal health policies]. PMID- 2332966 TI - [From Father Arthur's well to the knees of Mme. Germaine: the concept of primary health care]. PMID- 2332967 TI - [What is hidden behind the complaints in homes for the aged? Complaints and laments]. PMID- 2332968 TI - Interactions between neutrophils and platelets. PMID- 2332969 TI - Tissue distribution of an inducible cystatin in isoproterenol-treated rats. AB - A well-characterized, monospecific rabbit antiserum directed to an isoproterenol inducible type 2 salivary cystatin was used for immunocytochemical localization of this cystatin in rat salivary glands, as well as in other organs of normal and isoproterenol-treated rats. Immunocytochemical analysis revealed a moderate staining of secretory granules within the acinar cells of submandibular glands, which was more pronounced in tissues obtained from female rats. In addition, the inducible cystatin was readily detected within granular convoluted tubule cells and striated duct cells of submandibular glands of both male and female rats, although not all such structures were stained. Cystatin was also localized in the proximal convoluted tubule cells of the kidney in isoproterenol-treated female rats. Western blotting and Ouchterlony double diffusion analysis showed that the cystatin from submandibular gland and kidney extracts was immunologically identical. PMID- 2332970 TI - Atubular glomeruli in patients with chronic pyelonephritis. AB - In an animal model of chronic nephropathy a large proportion of the apparently normal glomeruli have been shown to be small and without connection to a proximal tubule. The present study examines the degree to which atubular glomeruli are also present in human renal disease. Eleven patients with chronic pyelonephritis (CP) and seven controls were investigated. The number of glomeruli connected to a normal proximal tubule was determined in serial sections and the volumes of individual glomeruli estimated with stereological methods. Only glomeruli with little or no sclerosis were investigated. The volume fractions of proximal tubules and interstitial tissue were estimated using point counting. The results showed that 50% of glomeruli in the CP group were connected to a normal proximal tubule, whereas 35% of the glomeruli were without any recognizable connection to a proximal tubule (atubular glomeruli). The remaining 15% were connected to an atrophic tubule. The mean volume of the glomeruli without a connection to a normal proximal tubule was only half that of glomeruli with a normal proximal tubule. No significant difference was found between the mean glomerular volume in the two groups, but the intraindividual variation of glomerular volumes was larger in the CP group. A significant negative correlation was found in the CP group between the percentage of glomeruli without connection to a normal proximal tubule and the volume fraction of proximal tubules. A significant positive correlation was found between the percentage of glomeruli that were not connected to a normal proximal tubule and the volume fraction of the interstitial tissue. This study shows that atubular glomeruli, which only can be identified in serial sections, constitute a large proportion of glomeruli in chronic pyelonephritis. Their existence could be a major reason for the irreversibility of nonglomerular chronic renal diseases. PMID- 2332971 TI - Unconventional lymphocytes involved in rejection of xenogeneic heart grafts. AB - In this report, the efficacy of cyclosporine A and two monoclonal antibodies, anti-L3T4 and anti-Lyt-2.2, was assessed on first-set rejection of cardiac xenografts. Neither cyclosporine nor anti-Lyt-2.2 monoclonal antibody prolonged the survival of heart xenografts. Anti-L3T4 enhanced acceptance of rat hearts transplanted to C57BL/6 mice 5-fold relative to that observed in control recipients; it did not, however, prolong acceptance of hamster hearts transplanted to mice. Histologic analysis indicated that the cellular infiltrate within rejected hearts was composed of greater than 95% lymphocytes; of these, greater than 99% were Thy-1- and sIg-. These results suggest that rejection of xenogeneic hearts is mediated by unconventional lymphoid cells. This is discussed in the context of whether rejection of allografts and xenografts occur by similar or dissimilar mechanisms. PMID- 2332972 TI - Type VI collagen. In situ hybridizations and immunohistochemistry reveal abundant mRNA and protein levels in human neurofibroma, schwannoma and normal peripheral nerve tissues. AB - Cutaneous neurofibromas contain an extensive extracellular matrix composed of collagenous and non-collagenous macromolecules. In this study, the expression of type VI collagen genes in cutaneous neurofibromas was examined by a combination of in situ hybridizations and immunohistochemistry. In situ hybridizations with a 32P-labeled human type VI collagen-specific cDNA revealed that the majority of cells within neurofibromas expressed the gene for alpha 2(VI) collagen chain. The number of cells expressing clearly detectable levels of alpha 2(VI) collagen mRNA was considerably higher than that of cells actively expressing the pro alpha 1(I) or pro alpha 1(III) collagen genes. The presence of type VI collagen epitopes within the neurofibromas was also demonstrated by immunostaining with specific polyclonal antibodies. The expression of type VI collagen genes in neural tissues was further examined by immunostaining of a benign schwannoma tissue specimen consisting of Schwann cells. The results indicated close association of type VI collagen epitopes with the neoplastic Schwann cells. Immunolocalization of type VI collagen epitopes within normal human peripheral nerve revealed pericellular staining of perineurial cells and Schwann cells, suggesting synthesis of type VI collagen by these cell types. These results suggest that the expression of type VI collagen gene is active in nerve-derived tissues, and that type VI collagen may be a major component of the extracellular matrix in neural connective tissues. PMID- 2332973 TI - The V-word and the four C's. PMID- 2332974 TI - On the role of alcohol in nonvehicular unintentional injuries among adolescents. PMID- 2332975 TI - Obstetrics and obstetrical care providers in rural east Tennessee. PMID- 2332976 TI - The birth, childhood and early adolescence of SVMIC. PMID- 2332977 TI - Radiology case of the month. Spontaneous splenic rupture in a patient with infectious mononucleosis. PMID- 2332978 TI - Pericarditis following antiarrhythmic therapy. PMID- 2332979 TI - Results of immunization surveys. PMID- 2332980 TI - Methodology and instrumentation for the in vitro sinus node recovery time determination. AB - In the present work we describe a methodology and a low-cost instrument to determine the sinus node recovery time (SNRT) in the isolated rat right atrium. The instrumentation measures the SNRT using the continuous pacing method and the method of stimulation with premature pulses. When these methods were compared, we observed that the corrected SNRT (CSNRT = SNRT - the mean spontaneous cycle length, MCL) significantly (p less than 0.001) depended on the method used. The effects of norepinephrine (NE) and acetylcholine (ACh) on MCL and CSNRT were also analyzed. Although both neurotransmitters affected MCL (p less than 0.001), only in the presence of ACh a significant (p less than 0.05) correlation between CSNRT and MCL was found. In both methods, the CSNRT values were quite reproducible. The agreement between the data obtained and the predictions of the theoretical models for in vivo SNRT determination suggests that the present methodology may be useful for studies concerning physical and chemical influences on SNRT, as well as for the development of new stimulation tests. PMID- 2332981 TI - Programmed electrical stimulation after myocardial infarction and reperfusion in conscious dogs. AB - The hemodynamic and electrophysiologic variables and the inducibility of arrhythmias were studied before coronary artery occlusion (CAO, 4h) and on days 4, 14, and 28 of the late reperfusion phase in conscious, chronically instrumented dogs. Despite a lack of significant changes in the hemodynamic and the electrophysiologic variables, the response to programmed electrical stimulation (PES) before and after CAO with subsequent reperfusion varied substantially. Before intervention arrhythmias such as sustained ventricular tachycardia (SVT) or ventricular fibrillation (VFib) could not be induced by PES via ultrasonic crystals located subendocardially (LAD and LCX region) or via common stimulation electrodes (right ventricle) in any of six instrumented animals. All six animals were inducible after CAO and reperfusion. Five animals showed SVT and one animal showed VFib in response to stimulation on days 4 and 14 of the late reperfusion phase after CAO. On day 28 four animals showed SVT, and two showed VFib. Antiarrhythmic drug testing carried out in the late reperfusion phase with lidocaine (1 mg/kg bolus followed by continuous infusion) revealed 50% efficacy at a dosage of 40 micrograms/kg/min, 100% at 80 micrograms/kg/min, and 67% at 120 mu/kg/min. The persistent inducibility of arrhythmias for the entire experimental period of 24 days may be attributable to the following features of our model: 1. Electrical stimulation carried out from three different locations. 2. The use of up to three extrastimuli in the PES studies. 3. The use of conscious dogs during CAO, reperfusion, and PES. This novel experimental approach thus promises to be of clinical relevance for the investigation of new antiarrhythmic drugs. PMID- 2332982 TI - Propafenone kinetics in the horse. Comparative analysis of compartmental and noncompartmental models. AB - The propafenone kinetics after intravenous (i.v.) administration have been studied in the horse by a comparative analysis of compartmental and noncompartmental models. The pharmacokinetic parameters showed a large distribution (Vdss = 1021 +/- 211 L) and a high clearance (CI = 7019 +/- 1746 mL/min) of the drug. The plasma concentrations were very low, under 1 microgram/mL, in most cases; after 30 min these concentrations can be considered as nonefficient for the treatment of arrhythmia. There were no significant differences between pharmacokinetic parameters found with the use of compartmental and noncompartmental models. PMID- 2332983 TI - A dual electrophysiologic test for atrial antireentry and ventricular antifibrillatory studies. Effects of bethanidine, procainamide, and WY-48986. AB - We have developed a dual electrophysiologic test that allows measurement of both antireentry and antifibrillatory activities of potential antiarrhythmics in the same anesthetized dog. The reentry portion of the model was created surgically by a Y-shaped crushing around the tissue between the superior and inferior vena cava and tissue parallel to the AV groove. The pacing-induced tachycardia that results from circus movements around the tricuspid ring is very persistent in duration and regular in cycle length. The antifibrillatory activities were assessed by determination of the ventricular fibrillation threshold (VFT) using train-stimuli method. Control VFT was measured every 15-20 min in duplicate and followed by induction of atrial reentry. A drug was infused to intervene the atrial tachycardia. After the conversion of the arrhythmia (either by drug regimens or pacing), postdrug VFT was measured, again in duplicate. Bethanidine (20 mg/kg), procainamide (30 mg/kg), and WY-48986 (10 mg/kg), a Class III antiarrhythmic, were evaluated in this dual test. Bethanidine and procainamide prolonged the cycle length of atrial reentry to a greater extent than WY-48986. The atrial arrhythmias were consistently terminated by procainamide and WY-48986 whereas bethanidine converted the tachycardias in one of the five dogs studied. All three agents elevated VFT with bethanidine producing higher values than procainamide and WY-48986. In conclusion, the dual electrophysiologic testing system offers both economic and scientific advantages for the study of modes of action of antiarrhythmic agents. PMID- 2332984 TI - Changing patterns of radiosensitivity of hematopoietic progenitors from chronically irradiated dogs prone either to aplastic anemia or to myeloproliferative disease. AB - Hematopoietic patterns have been assessed in chronic 60Co gamma irradiated dogs during preclinical phases of evolving aplastic anemia (AA) or myeloproliferative disease (MPD), principally myeloid leukemia. Within the AA-prone dog, a singular phase of progressive decline in blood levels of granulocytes and monocytes was noted along with a similar reduction in marrow progenitors committed to granulocyte/monocyte differentiation (CFU-GM). Measured radioresistance of the preAA CFU-GM in vitro, relative to control CFU-GM from nonirradiated animals, revealed only slightly increased resistance to gamma rays, but significantly increased resistance to fission neutrons. Within the MPD-prone dogs, four preclinical phases (i.e. suppression, partial recovery, accommodation, and preleukemic transition) preceding development of overt MPD were evidenced by the monitored change in blood granulocyte/monocyte counts and marrow progenitor levels. Analysis of radioresistance of preMPD CFU-GM revealed marked changes with time of exposure and, in turn, with preclinical phase transitions. Gamma ray resistance increased in the initial phases of exposure, with maximal levels occurring during the middle phase of exposure (accommodation, phase III) followed by a tailing off of resistance at later times. Resistance to fission neutrons by preMPD CFU-GM was observed as well, but somewhat later in the exposure course and at a much lower, more consistent level. These differential patterns of radioresistance expressed by marrow CFU-GM of chronically irradiated MPD-prone dogs to gamma rays and fission neutrons gave rise to preclinical phase-specific 'relative biological effectiveness' (RBE) values. From these observations, we conclude that: (i) CFU-GM of MPD-prone dogs acquire and maintain marked radioresistance to low linear energy transfer (LET) gamma rays, but only marginally elevated radioresistance to high-LET fission neutrons during the course of chronic gamma ray exposure; and (ii) CFU-GM of the AA-prone dog, in contrast, acquire little change in resistance to gamma rays, but, surprisingly, marked resistance to neutrons relative to progenitors from nonirradiated controls. These results support the concept that acquired radioresistance of vital granulocyte/monocyte lineage-committed hematopoietic progenitors is temporally, perhaps causally, linked to the processes mediating hematopoietic recovery and accommodation under chronic irradiation, and in turn to preclinical events of evolving MPD. In addition, the marked differential responses of progenitors to gamma and neutron irradiation in vitro might suggest differences in the nature of cellular lesions elicited by chronic gamma irradiation, in vivo. PMID- 2332985 TI - Acute myelofibrosis: response to recombinant human interferon alpha-2a. AB - Acute myelofibrosis is a rare myeloproliferative syndrome characterized by bone marrow proliferation of atypical megakaryocytes, poor response to conventional leukemic therapy, and a fulminant clinical course. Because alpha interferon exhibits potent antiproliferative effects against megakaryocyte progenitors and human fibroblast cell lines, we treated two patients with acute myelofibrosis or the related syndrome of acute myelodysplasia with myelofibrosis with recombinant human interferon alpha-2a. Patient 1 received a 12-week course of interferon alpha (1-6 x 10(6) IU/d) after failure of two cytarabine-based chemotherapy regimens. Interferon administration resulted in prompt improvement in symptoms, stabilization of leukocyte count, and a reduction in circulating blast forms. Primary treatment with interferon (1-3 x 10(6) IU/d x 4 weeks) in patient 2 produced complete hematologic recovery with restoration of marrow cellularity and reduced marrow fibrosis. Our findings suggest that interferon alpha may have significant activity in the treatment of patients with acute myelofibrosis. PMID- 2332986 TI - Prognostic significance of glucocorticoid receptor determination in patients with chronic lymphocytic leukemia and immunocytoma--lack of a positive correlation between receptor levels and clinical responsiveness. AB - Glucocorticoid receptors (GR) have been suggested to have prognostic significance in patients with CLL treated with chemotherapy containing glucocorticoid. In this study, the GR levels in 65 patients with advanced CLL and immunocytoma (clinical stages III and IV according to Rai) were determined by means of a whole cell assay. The median GR-level was 1,920 bs/c with a range from 0 to 9591. The patients were subsequently treated according to a prospective, randomized trial with either a combination of chlorambucil and prednisolone, or with prednimustine. No significant difference in receptor levels was found between responders (median = 1940 bs/c; n = 47) and nonresponders (median = 1950 bs/c; n = 14). To assess the influence of receptor content on prognosis we have analyzed the relationship between GR content and survival time and duration of response. There was no significant difference in duration of response and in survival between those patients with high (greater than 1920 bs/c) and those with low GR levels (less than 1920 bs/c) (log-rank test). Our data suggest that determination of GR provides no reliable indicator for clinical response to regimens with glucocorticoid as a component in patients with CLL and immunocytoma. PMID- 2332987 TI - Alpha-L-fucosidase isoenzyme pattern in hairy cell leukaemia. AB - alpha-L-Fucosidase isoenzymes pattern in hairy cell leukaemia (HCL) is characterized by the disappearance of the more acidic form when compared to normal lymphocytes. Our data seem to indicate that this profile could not be related to the T or B phenotype because in normal lymphocytes (mainly T), MO cells possessing T markers, as well as lymphocytes from chronic lymphoid leukaemia (CLL) known to exhibit normal-like B phenotypes two alpha-L-fucosidase forms are identified and especially the more acidic one. PMID- 2332988 TI - Phorbol myristate acetate induces both high affinity and low affinity interleukin 2-receptors on a pre-B leukemic cell line. AB - The human pre-B leukemic cell line Reh6 does not constitutively express the Tac molecule (p55), which is one of the two polypeptide chains of the interleukin 2 receptor (IL2-R). Cell incubation with Phorbol Myristate Acetate (PMA) induces expression of the Tac molecule in a dose and time-dependent manner. Binding experiments with radiolabelled recombinant IL2 (rIL2) revealed both high and low affinity IL2-R (225 +/- 105 sites/cell with a Kd of 130 +/- 51 pM and 24060 sites/cell with a Kd of 17.3 nM respectively), whereas unstimulated Reh6 cells only expressed intermediate affinity Reh6 cells revealed the presence of two polypeptide chains of mol. wts 55,000 (Tac molecule) and 70,000, as in normal activated T cells, while the 70,000 mol. wt chain alone was observed in unstimulated Reh6 cells. IL2-R-bearing Reh6 cells could absorb rIL2 in a dose dependent manner and this absorption was inhibited by a monoclonal antibody against the Tac molecule (anti-Tac). Moreover, partial internalization of IL2 bound under high affinity conditions occurred at 37 degrees C. IL2-R expressed on PMA-induced cells were functional since rIL2 specifically enhanced the proliferation in vitro of PMA-treated cells in semi-solid but not liquid cultures. These findings thus demonstrate an IL2-dependent mechanism of proliferation in vitro of pre-B leukemic cells induced by PMA, which can express high affinity, functional IL2-R. PMID- 2332989 TI - Cell type dependent activation of poly (ADP-ribose) synthesis following treatment with etoposide. AB - Treatment of human non-lymphoid cell lines, HL-60 and U937, with etoposide stimulated poly (ADP-ribose) synthesis three- to fourfold, whereas no significant effects were observed in the lymphoid cell lines, Molt4 and CEM. This was confirmed by either an increased uptake of radio-labelled NAD into the acid insoluble fraction or a fall in cellular NAD levels, which was counteracted by 3 aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase. On the other hand, another DNA damaging agent, N-methyl-N'-nitro-N-nitrosoguanidine augmented poly(ADP-ribose) synthesis equally in both cell types. These results taken together indicate that the activation of poly(ADP-ribose) synthesis following exposure to etoposide is a cell type specific phenomenon. PMID- 2332990 TI - Susceptibility of acute myeloid leukemia (AML) cells from clinically resistant and sensitive patients to daunomycin (DNR): assessment in vitro after stimulation with colony stimulating factors (CSFs). AB - Chemosensitivity of purified AML blasts to daunomycin was examined under conditions of CSF stimulation and compared with clinical outcome of DNR combination chemotherapy. AML blasts from 16 patients were purified, incubated serum-free in the presence of optimal concentrations of a complete cocktail of IL 3, GM-CSF and G-CSF to provoke cell proliferation maximally, and DNR drug sensitivity in vitro was assessed by inhibition of DNA synthesis in response to titrated DNR concentrations. The sensitivity of proliferating AML cells to DNR did not correlate with the clinical response of the patients as identical dose response curves were obtained for complete responders (n = 6), partial responders (n = 5) and resistant cases (n = 5). As a major part of the AML population was induced to enter DNA synthesis in vitro, these data suggest that the manoeuvre of cell cycle stimulation has abrogated cellular resistance to daunomycin and rendered in vivo, apparently refractory cells susceptible to the anthracycline. PMID- 2332991 TI - Pancreas transplantation at Mayo: II. Operative and perioperative management. AB - Better perioperative and operative management techniques have contributed to an improvement in the success rate of pancreas transplantation. Because of a shortage of donor organs, the criteria for acceptability of the allograft have been liberalized, and the development of techniques such as combined liver and pancreas procurement has increased allograft availability. Major advances have been made in organ preservation. Currently, pancreas allografts can routinely be stored for 18 to 24 hours. The technique of pancreaticoduodenal transplantation with a duodenocystostomy for the exocrine drainage is widely used. Experience with anesthetic and intensive-care unit management of these patients is accumulating. With the evolution of pancreas transplantation and with the help of the excellent transplant centers in our area, we developed a pancreas transplantation protocol and performed transplantation based on this protocol in 16 recipients at the Mayo Clinic from October 1987 through December 1988. PMID- 2332992 TI - Pancreas transplantation at Mayo: III. Multidisciplinary management. AB - Although pancreas transplantation is a complicated procedure, a good level of success has been achieved because of the introduction of cyclosporine for immunosuppression, improved methods for diagnosing rejection, and a multidisciplinary approach to management. Our immunosuppressive regimen was quadruple therapy with induction by using Minnesota antilymphoblastic globulin. A biopsy technique was instituted in which the pancreas specimens were obtained under cystoscopic direction during episodes of hypoamylasuria. The criteria for rejection episodes were not only biochemical abnormalities but also histologic confirmation and a follow-up to exclude other causes of graft dysfunction. Infectious disease management included use of oral selective bowel decontamination for 3 weeks after transplantation. At the Mayo Clinic between October 1987 and December 1988, 16 patients received pancreaticoduodenal allografts (both kidney and pancreas in 13 and pancreas only in 3 after a prior successful kidney transplantation). In two pancreas and one kidney allograft, function was lost. One patient died of multiorgan failure. The cystoscopically directed biopsy technique was performed 23 times with minimal complications and a 93% success rate. The metabolic results have been excellent; the glycosylated hemoglobulin level was normal 3 to 6 months after transplantation. The quality of life was significantly improved in almost all patients. Nutritional assessment revealed little deterioration after transplantation. With a multidisciplinary approach, the needed answers about the effect of pancreas transplantation on the degenerative complications of diabetes should be forthcoming. PMID- 2332994 TI - Reperfusion in acute myocardial infarction. AB - During the past decade, the general acceptance of the primary role of thrombosis in acute myocardial infarction (AMI) has led to intense interest in the potential efficacy of reperfusion therapy, particularly thrombolytic therapy, in AMI. Accumulating evidence indicates that systemic thrombolytic therapy administered early after the onset of symptoms of AMI can restore infarct-related artery patency, salvage myocardium, and reduce mortality. Recommendations about the proper use of thrombolytic therapy, contraindications, and concomitant therapies (such as aspirin, heparin, nitrates, beta-adrenergic blocking agents, and calcium channel blockers) are reviewed. Although percutaneous transluminal coronary angioplasty (PTCA) is useful for subsets of patients with AMI (for example, patients with anterior infarctions with persistent occlusion of the infarct related artery after thrombolytic therapy and those with cardiogenic shock), a conservative strategy, including angiography and PTCA only for postinfarction ischemia, is indicated for most patients with AMI in whom initial thrombolytic therapy is apparently successful. The use of PTCA after failed thrombolysis or as direct therapy for AMI seems promising, although further comparisons of PTCA and intravenous thrombolytic therapy are needed. Ongoing studies should help further define the risk-to-benefit ratio of various reperfusion strategies in different subsets of patients, define time limitations for reperfusion therapy, and provide data on therapeutic modalities that will limit reperfusion injury and therefore enhance salvage of myocardium. PMID- 2332993 TI - Pulmonary complications from ophthalmic preparations. AB - Topical beta-adrenergic blocking agents are commonly used to treat glaucoma. Exacerbations of asthma and bronchospasm caused by topical beta-adrenergic ophthalmic preparations are well known. We describe a 67-year-old woman who had aspiration pneumonitis characterized by a nodular infiltrate in the right middle lobe of the lung and nocturnal coughing after beginning topical application of an ointment (Lacri-Lube) for treatment of xerophthalmia. Bronchial washing demonstrated lipid-laden pulmonary alveolar macrophages. After the use of Lacri Lube was discontinued, her cough and the chest roentgenographic abnormality totally disappeared. We postulate that the topical ophthalmic preparation, which contains mineral oil and petrolatum, drained into the nasopharynx, trachea, and bronchial tree through the nasolacrimal duct and caused lipoid pneumonitis from aspiration of the oil contents. To our knowledge, this is the first report of pulmonary complications caused by Lacri-Lube. We briefly review the pulmonary complications, including pulmonary edema, apnea from paralysis of respiratory muscles, bronchospasm from non-beta-adrenergic blocking drugs, and electrolyte abnormalities, attributable to topically and systemically administered ophthalmic medications. PMID- 2332995 TI - Changes in the anatomy and function of the maternal anterior pituitary gland during pregnancy. PMID- 2332996 TI - Therapeutic "cloggology". PMID- 2332997 TI - Thrombogenic potential of nonionic contrast media. PMID- 2332998 TI - Effects of Nd: YAG laser coagulation of myocardium on coronary vessels. AB - Laser coagulation of arrhythmogenic myocardium proved to be an effective surgical therapy for refractory arrhythmias. To determine the influence of Nd: YAG laser coagulation of myocardium on coronary vessels, a total of 48 transcatheter laser impacts (10 W, 10 sec, 7 W mm2) were directed to the left ventricular free wall via endocardial (24 lesions in 2 dogs) or epicardial (24 lesions in 2 dogs) approach. In 8 of 24 endomyocardial lesions (2 and 6 months old) coronary vessels with a diameter of greater than 50 microns were found within the coagulation zones. The volume of these lesions was significantly (P less than 0.01) smaller (139 +/- 43 mm3) than those (n = 16) with coronary vessels measuring less than 50 microns (311 +/- 87 mm3). Volumes of epimyocardial lesions (1-2 hours old) produced by transcoronary irradiation with normal coronary blood flow were significantly (P less than 0.01) smaller (31 +/- 17 mm3) than with reduced (73 +/ 22) or interrupted (119 +/- 34 mm3) blood flow (n = 8, each). Both directly irradiated coronary vessels and those found within the coagulation zones and scars appeared histologically normal through all layers with an intact intima without fibrosis or thrombosis. The ultrastructure of irradiated arteries, even with total interruption of blood flow, was no different from that of non irradiated controls. Thus, coronary artery blood flow significantly reduces the volume of coagulated myocardium, whereas the vessels themselves appear to remain undamaged by laser irradiation as used for myocardial coagulation. PMID- 2332999 TI - Percutaneous transcatheter laser balloon ablation from the canine coronary sinus: implications for the Wolff-Parkinson-White syndrome. AB - Transcatheter direct current electrical shocks for ablation of left-sided accessory pathways in Wolff-Parkinson-White patients have led to serious complications. We report the feasibility of percutaneous transcatheter laser balloon ablation of left-sided accessory pathways from the coronary sinus using a 1,064-nm, continuous wave Nd:YAG laser triple lumen catheter with an optical fiber terminating in a cylindrical diffusing tip within a 2-cm-long, 3-mm diameter balloon transparent to Nd:YAG laser radiation. In eight mongrel dogs (18 to 31 kg), the laser balloon catheter was positioned via an 8 French guide catheter in the distal and proximal coronary sinus. During balloon inflation, two to three consecutive laser doses of 30 W x 20 sec were applied to each site (cumulative energy, 1,200 to 1,800 J). Coronary angiography, left ventriculography, and coronary sinus injection were performed before and after laser exposure. After percutaneous transcatheter laser balloon ablation, there was no evidence of mitral regurgitation, left circumflex artery, coronary sinus obstruction, or perforation. Coagulation necrosis and/or polymorphonuclear infiltrates involving the atrioventricular groove and left atrial wall over a mean length of 17 mm were present in all eight dogs sacrificed 6 +/- 1 hr postablation. In conclusion, percutaneous transcatheter laser balloon ablation from the coronary sinus is free of immediate major complications and may be feasible for potential interruption of left-sided accessory pathways. PMID- 2333000 TI - Traumatic tattoo removal: comparison of four treatment methods in an animal model with correlation to clinical experience. AB - The acute or emergency treatment of traumatic tattoos has been based on the principles of immediate and thorough removal of all particles. The delayed treatment of traumatic tattoos has classically been with overgrafting or dermabrasion. We developed an animal model for traumatic tattoos. Two levels of wounds were made (shallow and deep). Each group consisted of five guinea pigs with one consistent level of wounding. Four treatment methods were applied: carbon dioxide laser, argon laser, overgrafting, and dermabrasion. The results were evaluated by trained observers on a gross basis. Although no statistically significant differences were found within these small groups, clinical experience in a small group of patients suggests that carbon dioxide laser may prove to be useful in the delayed treatment of traumatic tattoos. Eight patients have been treated over a 4-year period. Satisfactory total or subtotal foreign body removal of various agents (road tar, cement, cooper particles) has been achieved. PMID- 2333001 TI - Photodynamic therapy: tumor volume limitation and tumor response for murine fibrosarcoma. AB - The clonogenic survival rates and tumor growths following photodynamic therapy (PDT) were studied as a function of tumor volume for RIF-1 using C3H mice as an animal model. The clonogenic survival rates showed a saturation level approaching a 99.8% survival rate for large volumes (above 1,900 mm3), possibly indicating poor light utilization of 630 nm because of the limited tissue penetration and/or tumor hypoxia. With a small tumor volume [less than 150 mm3], the survival rate (less than 0.3%) showed an exponential increase with volume. The survival rates (less than 0.03%) corresponding to a volume lower than 50 mm3 gave complete tumor eradication. On the other hand, partial response and recurrence were noticed with volumes larger than 90 mm3, which had more than approximately 0.1% survival rates. After PDT, all tumors responded with immediate swelling and skin discoloration, followed by necrosis, tumor delay, and regrowth. Regrowth rate and tumor cell doubling time were slower than the control growths and decreased further following superficial irradiation with a second interstitial illumination. The regrowth rates were slow for small initial tumor volumes and fast for large initial tumor volumes. Also, the delay period was longer for the small initial tumor volumes in comparison to a shorter period for the medium tumor volumes and very low probability of delay for the large volumes. PMID- 2333002 TI - Combination studies of hyperthermia induced by the neodymium: yttrium-aluminum garnet (Nd:YAG) laser as an adjuvant to photodynamic therapy. AB - Photodynamic therapy (PDT) and hyperthermia have been investigated as treatments for several types of tumors. Studies have been done to determine the efficacy of each modality individually and recently in combination with each other. In this study, 630-nm light was delivered by an argon-dye laser and hyperthermia was induced using an Nd:YAG laser. Both lasers offer the ability of delivering the beams through a quartz fiberoptic alone or simultaneously. This study examines the efficacy of the simultaneous administration of PDT and selective hyperthermia at 44.5 degrees C in tumor control in the spontaneous mammary tumor (SMT-F) in DBA mice. Hyperthermia alone (44.5 degrees C, 30 min) resulted in complete destruction of tumors, with no subsequent regrowth in 6.6% of the mice treated. PDT alone (5 mg/kg dihematoporphyrin ether; 135 J/cm) resulted in a cure rate of approximately 10%, and the simultaneous treatment of the modalities resulted in a 32.8% cure rate after 90 days. These values are indicative of a synergistic interaction. PMID- 2333003 TI - Sutureless end-to-end bowel anastomosis using Nd:YAG and water-soluble intraluminal stent. AB - Sutureless end-to-end intestinal anastomoses were successfully constructed in 20 rabbits. A water-soluble intraluminal stent was used to approximate the tissue edges, and the anastomotic seam was lased with 1.06 microns neodymium:YAG (Nd:YAG) laser energy supplied through a hand-held 600-microns gas-cooled noncontact optical fiber. A continuous 5-watt wave of power was applied over periods ranging from 46 to 92 seconds to produce the tissue blanching and shrinkage that indicated a satisfactory tissue weld. Integrity, degree of tissue reaction, and bursting pressures of the anastomoses were compared to those of anastomoses constructed using standard sutured techniques. The results of the two methods were equivalent at 1 to 3 days, but the laser-fused enteric anastomoses showed less inflammatory reaction and greater bursting pressures at 7 and 14 days. Application of a variety of proteinaceous solutions including extracellular matrix materials and epidermal growth factors prior to lasing failed to augment wound healing. We conclude that lasers show promise as reconstructive, in addition to ablative, surgical instruments. PMID- 2333004 TI - Continuous laser radiation effect at 1.06 microns on gastrointestinal tract. AB - The thermal effect of 1.06 microns YAG:Nd laser irradiation at temperature conditions up to 100 degrees C without crater formation on gastrointestinal (GI) tissue samples was investigated. The theoretical and experimental data show that at an intensity of 160-400 W/cm2 laser-induced heating of the tissue with an initial temperature of 20 degrees C leads to coagulation lesions at a temperature no less than 60 degrees C and at a depth of 1.7-2.1 mm. PMID- 2333005 TI - Epilation of hair-bearing urethral grafts utilizing the neodymium:YAG surgical laser. AB - Non-hair-bearing skin should be utilized when grafting is necessary in carrying out urethroplasty for stricture or hypospadius repair. Occasionally this is not possible, or hair-bearing skin is used inadvertently. Traditionally electrocoagulation has been the method used for epilation when intraluminal hair has become a problem, such as interfering with flow, being foci for recurring urinary tract infection, or acting as a nidus for calculus formation. Electrocautery is also used at the time of grafting in an attempt to prevent the growth of hair when hair-bearing skin is utilized. Unfortunately, because of lack of penetration, the hair follicles are not destroyed and the epilating procedure fails or is only partially successful. The neodymium: YAG (Nd:YAG) surgical laser can photocoagulate tissue to a depth up to 5.0 mm and thus has the ability to destroy hair follicles. We report three cases presenting with clinical problems directly related to hair-bearing urethral grafts successfully treated by Nd:YAG epilation. PMID- 2333006 TI - Nd:YAG coagulation of the verumontanum: an endoscopic attempt at sterilization. AB - In order to develop a new and less invasive method of sterilization in men we performed photocoagulation of the verumontanum in 10 rams, using a Nd:YAG laser, wavelength 1,060 nm. Under general anesthesia a perineal urethro-cutaneous fistula was achieved, and, by means of a 16F laser-endoscope, transurethral coagulation of the ejaculatory ducts, located in the verumontanum, was carried out, using pulses of 1.5 sec in duration and 20-30 W in power. The animals were killed at different postoperative time intervals, ranging from 1 day to 8 weeks. Injection of methylene-blue into the testicular ducts of the resected prostate bladder specimen and histologic studies of the coagulated tissue revealed that complete bilateral occlusion of the ejaculatory ducts had been achieved in 4 rams. Failures were due to over-extended irradiation of the verumontanum. Except for urinary tract infections occurring in 4 animals, no serious complications were encountered. Further investigations are still necessary to determine the role of lasers in male sterilization. PMID- 2333007 TI - Laser photobioactivation mechanisms: in vitro studies using ascorbic acid uptake and hydroxyproline formation as biochemical markers of irradiation response. AB - Clinical investigations of laser photobioactivation, or biostimulation, might be differently designed and more fruitful if knowledge of basic biochemical mechanisms were better understood. In this investigation, biochemical events identified as responses to 904 nm irradiation included increased ascorbic acid uptake by fibroblasts. These cells also showed increased hydroxyproline formation, and this was increased several-fold by the addition of proline to the medium. Maximum biochemical responses were observed at a pulse frequency of 67 Hz and a pulse width of 150 nsec with an energy density of approximately 7 mJ/cm2 per exposure. Elements in the mitochondrial cytochrome system are proposed as the radiation absorbing chromophore(s). Hypothetically, the energy generated is linked to ascorbic acid uptake, which in turn stimulates collagen synthesis. PMID- 2333008 TI - Long-term survival of a lung cancer patient treated with photodynamic therapy. AB - A 63-year-old male, status post-right pneumonectomy, presented with hemoptysis. Although chest X-ray and CAT scan film findings were negative, bronchoscopy with biopsy from the left mainstem bronchus demonstrated squamous cell carcinoma. Because of the inoperable location of the lesion, the patient was treated with photodynamic therapy (PDT) in February 1984. At present, the patient is cancer free more then 6 years after PDT. PMID- 2333009 TI - ["Sense and nonsense in non-surgical gallstone treatment"]. PMID- 2333010 TI - [The significance of papillary biopsy in obstruction of Vater's papilla]. AB - Biopsies of the papilla of Vater were taken in 53 patients after a papillotomy had been carried out during a previous ERC. The macroscopic finding of a papillary stenosis of unknown dignity required an exact histological diagnosis. In 35 patients (66%) a duodenitis/papillitis was found on the histological specimens, in 6 patients (11%) a villous adenoma, and in 7 patients an adenocarcinoma (13%). A metastasis of a melanoma, a schwannoma, and a coagulum were diagnosed once. The papillotomy preceding the biopsy was the only necessary therapy in 46 patients, and endoprosthesis was inserted in 5 patients. In 2 patients the tumor was excised by snare, in 4 patients a surgical resection was carried out. The incidence of malignancy in papillary stenosis emphasizes the significance of a biopsy for histological confirmation of the diagnosis if endoscopically a papillary stenosis is detected. PMID- 2333011 TI - [Diffuse eosinophilic gastroenteropathy]. AB - Eosinophilic gastroenterocolitis is a very rare disease of the gastrointestinal tract. As a result, frequently the diagnosis is missed and/or symptoms get misinterpreted. Histological examination and blood analysis however support the finding of the correct diagnosis in most cases. We report here the case of a 47 year old female patient with diffuse gastroenterocolitis and we will comment the diagnostic problems. PMID- 2333012 TI - Identification of four brain areas each enriched in a unique muscarinic receptor subtype. AB - The affinities of muscarinic agonists and antagonists were determined by autoradiography and image analysis in selected areas of the rat brain. IC50 values and Hill coefficients for the inhibition of the binding of 0.2 nM [3H]-QNB to dentate gyrus, superior colliculus, rhomboid thalamus and substantia nigra were measured in coronal sections. Pirenzepine displayed a high affinity for receptors in the dentate gyrus and AF-DX 116, the superior colliculus. Both pirenzepine and AF-DX 116 had high affinities for the substantia nigra and low affinities for the rhomboid thalamus. Gallamine displayed a 50-fold preference for superior colliculus over dentate gyrus receptors. Amitriptyline was less selective, showing a modest preference for substantia nigra receptors and 4-DAMP was essentially nonselective. Carbachol was the most selective agonist with a 4000-fold preference for superior colliculus over dentate gyrus receptors. Other agonists except RS 86 were also selective for superior colliculus receptors in the order carbachol much greater than arecoline greater than bethanechol greater than McN A343 = oxotremorine = pilocarpine. PMID- 2333013 TI - Morphine formation from codeine in rat brain: a possible mechanism of codeine analgesia. AB - The O-demethylation of codeine to morphine was demonstrated in rat brain homogenate. Maximal formation occurred at 10 minutes, with a Vmax of 5.93 +/- 0.16 nmol/g brain/h and Km of 37.82 +/- 4.99 microM. The formation was significantly (P less than 0.05) greater in the microvessel-rich brain fraction. Intraperitoneal injection of codeine in the rat resulted in brain concentrations of morphine which could not be solely attributed to transfer of morphine from the blood stream across the blood-brain barrier. Morphine formed in the brain after codeine administration may be an important mechanism for codeine-induced analgesia. PMID- 2333014 TI - Lipid peroxidation in rat tissue slices: effect of dietary vitamin E, corn oil lard and menhaden oil. AB - Rats were fed for 5 weeks either 10% (w/w) menhaden oil (MO) or a 10% corn oil lard (COL) mixture (1:1) in diets with less than or equal to 5 IU or less than or equal to 2 IU/kg vitamin E, respectively, or the same diets supplemented with d alpha-tocopheryl succinate to a total of 35 and 180 IU vitamin E/kg, respectively. Slices of liver and heart from these rats were used to study lipid peroxidation in vitro. Thiobarbituric acid-reactive substances (TBARS) were measured in the medium after incubation of the slices at 37 degrees C for 1 hr in the absence (uninduced) and presence of 0.5 mM tert-butyl hydroperoxide (induced). The release of TBARS from slices of heart and liver from rats fed either lipid decreased with increasing levels of dietary vitamin E. At the same level of dietary vitamin E, TBARS release was greater for slices of liver and heart from the MO-fed rats than from the COL-fed rats. Application of the TBARS data to a model simulating the experimental conditions showed a good correlation (r = 0.95, p less than 0.001) between experimental and simulated values. Of the 16:0-22:6 fatty acids measured in liver from MO-fed rats, 15.4% was n-6 fatty acids and 29.9% was n-3 fatty acids; in liver from COL-fed rats, the respective values were 37.4% and 3.7%. Liver and kidney vitamin E levels were unaffected by the dietary lipid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333015 TI - Phosphatidylcholine synthesis in the rat: the substrate for methylation and regulation by choline. AB - Two lines of evidence led us to reexamine the possibility that methylation of phosphoethanolamine and its partially methylated derivatives, in addition to methylation of the corresponding phosphatidyl derivatives, plays a role in mammalian phosphatidylcholine biosynthesis: (a) Results obtained by Salerno and Beeler with rat [Salerno, D.M. and Beeler, D.A. (1973) Biochim. Biophys. Acta 326, 325-338] appear to strongly support such a role for methylation of phosphobases; (b) Such reactions have recently been shown to play major roles in phosphatidylcholine synthesis by higher plants [see Datko, A.H. and Mudd, S.H. (1988) Plant Physiol. 88, 854-861 and references therein]. We found that, following continuous labeling of rat liver with L-[methyl-3H]methionine for 10.4 min (intraperitoneal administration) or for 0.75 min (intraportal administration), virtually no 3H was detected in methylated derivatives of phosphoethanolamine, but readily detectable amounts of 3H were present in the base moiety of each methylated derivative of phosphatidylethanolamine. Thus, there was no indication that phospho-base methylation makes a significant contribution. Studies of cultured rat hepatoma cells showed definitively for the first time in a mammalian system that choline deprivation up-regulates the rate of flow of methyl groups originating in methionine into phosphatidylethanolamine and derivatives. Even under these conditions, methylation of phosphoethanolamine bases appeared to play a negligible role. PMID- 2333017 TI - April 1990. Rabies in Maryland. PMID- 2333018 TI - Current technology of in vitro fertilization and embryo transfer. AB - Since the initial human in vitro fertilization (IVF-ET) procedure in 1978, the laparoscope was the primary method for oocyte collection. Although laparoscopic retrieval instrumentation has been refined, ultrasound-guided follicular puncture has become the major retrieval technique in IVF-ET repertoire. The Johns Hopkins In Vitro Fertilization Program was initiated in 1984, recording the first in vitro pregnancy in Maryland. PMID- 2333016 TI - Carotenoids of human colostrum. AB - Colostrum, the initial postpartum secretion of the breast, ordinarily has a distinct yellow color due to carotenoids of its fat globules. This pigmentation progressively diminishes as milk production increases during the first week of lactation. Identity of these carotenoids was investigated by means of thin-layer chromatography, high performance liquid chromatography and spectral analysis. Alpha- and beta-carotene, lycopene and beta-cryptoxanthin were revealed as major chromogens. A component corresponding to lutein and/or zeaxanthin was also detected by both chromatographic techniques. Extracts of 23 saponified colostrum samples from 10 donors revealed considerable variation in total carotenoid concentration (0.34-7.57 micrograms/ml of colostrum). Multiparous mothers had greater mean colostrum carotenoid concentrations than did the primiparae, 2.18 +/ 1.94 vs 1.14 +/- 1.32 micrograms/ml, respectively. Seven of the eight primiparous donors' samples had little or no yellow color. These findings imply a difference in carotenoid transport by breasts that have lactated as compared to those that have not. The interrelation of carotenoids, lactation and breast cancer is discussed. PMID- 2333019 TI - Laser therapy in the treatment of congenital vascular abnormalities. AB - Portwine stains, especially on the face, have serious psychological and emotional impact for affected children. Laser therapy has been the only effective means for treating these lesions. The argon laser has been the mainstay, but more recently the flashlamp-pumped pulsed dye laser has added significantly to the management of portwine stains as well as to the effective treatment of other vascular lesions such as telangiectasias and angiomas. PMID- 2333020 TI - Genetic linkage studies of bipolar affective disorder. AB - Underrecognition and undertreatment of affective disorders constitute a serious public health problem in this country. The recent availability of improved methods of genetic linkage analysis make the definition of the genetic basis of some types of bipolar affective disorders feasible within the foreseeable future. PMID- 2333021 TI - Modern treatment of brain tumors. AB - Although there has been enormous improvement in the safety and accuracy of our diagnostic approaches and in the precision and safety of our surgical techniques, the long-term survival of patients with malignant brain tumors remains dismal. With an increased understanding of the fundamental biologic characteristics of brain tumors, we should be able to improve the outlook for these patients. PMID- 2333022 TI - Carcinoma of the pancreas: are we making progress? AB - Over the past several decades no disease has frustrated clinicians more than carcinoma of the pancreas. At the time of diagnosis most patients have been unresectable. Recent reports suggest that when resection is possible, pancreaticoduodenectomy can be performed safely and survival extended by adjuvant therapy. PMID- 2333023 TI - Management of sickle cell anemia in children. AB - Approximately 1 in 500 black American births results in children who have sickle cell (SS) disease; they are rarely symptomatic until 6 months of age. The mortality rate of SS in children under age 12 is between 10 and 15 percent. Half this mortality occurs before age 2, and most is due to overwhelming infections. PMID- 2333024 TI - Disorders of carbohydrate absorption in clinical practice. AB - The most important of the genetically determined causes of carbohydrate malabsorption, lactase deficiency, affects the majority of the world's adults. Management of carbohydrate malabsorption consists of temporary or permanent removal of the offending sugar from the patient's diet or providing the sugar in a more digestible form. PMID- 2333025 TI - Preservation of sexual function in men during radical pelvic surgery. AB - Recent neuroanatomical findings making it possible to intraoperatively identify the branches of the pelvic plexus that innervate the corpora cavernosa have been used to modify standard radical prostatectomy and cystoprostatectomy to prevent postoperative sexual dysfunction. PMID- 2333026 TI - Advances in diagnosis and treatment of glaucoma. AB - More changes have occurred in the last 10 years in the diagnosis and treatment of glaucoma than occurred in the previous 100 years. Emphasis in diagnosis and follow-up has shifted from measurement of the intraocular pressure to detection and assessment of damage to the optic nerve, objectively and subjectively. PMID- 2333027 TI - Alzheimer's disease research at Johns Hopkins. AB - The emergence of Alzheimer's disease from relative obscurity to front-page news is related to the increased life expectancy and increased proportion of the population over 65 years old. About 8 percent of the US elderly population suffer from the disease. PMID- 2333028 TI - Focus review: an old concept revisited. AB - Medical students throughout the world learn clinical skills in a physical diagnosis course. Clinicians can use this approach to design a focus review to serve as a method of evaluation in the quality assurance of healthcare and as a research tool. PMID- 2333029 TI - Update on medical control in EMS service. PMID- 2333030 TI - Update on the Board of Physician Quality Assurance. PMID- 2333031 TI - Oral hygiene and diabetes. PMID- 2333032 TI - Theiler's virus-induced demyelination in mice immunosuppressed with anti-IgM and in mice expressing the xid gene. AB - Intracerebral infection with Theiler's murine encephalomyelitis virus produces chronic immune-mediated demyelination in susceptible strains of mice. We examined the role of Ig in the pathogenesis of demyelination. In susceptible SJL/J mice (H 2s), suppression of B cell responses with IgG fraction of goat anti-mu (anti-mu IgG) from birth resulted in increased numbers and severity of demyelinating lesions in the spinal cord 35 days after infection. In contrast, treatment of resistant C57BL/10 (H-2b), C57BL/6 (H-2b), or B10.D2 (H-2d) mice with anti-mu IgG had no apparent effect since these mice did not develop demyelination or inflammation in the spinal cord following infection. Similar results were obtained with certain strains of B-cell deficient mice that exhibit the xid gene mutation. Male CBA/NJ (xid) showed increased meningeal inflammation and demyelination compared to male CBA/J mice. However, B6.CBAN, C3.CBAN, or C.CBAn mice showed no or minimal evidence of demyelination despite the presence of the xid mutation. In the SJL/J mouse, the majority of the humoral immune response to virus antigen was restricted to the IgG2b and IgM isotypes. These data indirectly support the hypothesis that immunoglobulins protect partially against development of virus-induced demyelination in susceptible but not resistant animals. In addition, the data argue strongly against the hypothesis that TMEV-induced demyelination is mediated predominantly by humoral autoimmune or humoral viral immune mechanisms. PMID- 2333033 TI - Variation in the molecular weight of PspA (pneumococcal surface protein A) among Streptococcus pneumoniae. AB - Pneumococcal surface protein A (PspA) has been shown to be a virulence factor of pneumococci and to elicit protective anti-pneumococcal antibodies in mice. PspAs from different pneumococcal isolates have been shown to exhibit antigenic variability. In previous studies with three strains, two different apparent molecular weights of PspA were observed. In this report we have studied the variation in molecular weight of PspA from 43 pneumococcal strains reactive with anti-PspA monoclonal antibodies, Xi64 and/or Xi126. The relative molecular mass (Mr) of the major PspA band ranged from 67 k to 99 k in the different strains. Variations in Mr of PspA were observed even within strains of the same capsular type. The molecular size of PspA from strain Rx1 was not affected by treatment with a variety of chemical, enzymatic, and physical procedures, suggesting that the differences in Mr of PspA among different strains, was not due to uncontrolled variations in PspA preparation. The Mr of PspA of a given strain was found to be stable both in vivo and in vitro. As a result variations in the Mr of PspA from clinical isolates, should allow discrimination between strains within a given capsular type in epidemiologic studies. PMID- 2333034 TI - Growth of canine distemper virus in cultured astrocytes: relationship to in vivo persistence and disease. AB - Canine distemper virus (CDV) causes an encephalomyelitis in dogs which varies with the viral strain. The CDV Cornell A75-17 strain produces a delayed, subacute to chronic, demyelinating CNS disease. In contrast, the Snyder Hill (CDV-SH) strain-associated neurological disease is more acute in onset, is usually non demyelinating and primarily produces lesions in the gray matter. In these studies we describe the effects of these two virulent and one avirulent CDV strain, Rockborn (CDV-RO), on astrocytes in dissociated canine brain cell cultures. In multiple replicate experiments, astrocytes were infected most rapidly by CDV-RO [100% of astrocytes were infected by 14 days post-inoculation (p.i.)]. This strain caused severe cytopathic effect (CPE) and cytolysis. CDV-SH similarly produced a rapid infection of the astrocytes. In contrast, CDV A75-17 infected less than 25% of the astrocyte population during the first 28 days p.i. (+/- 7 days); after 28 days p.i., a rapid rise in astrocyte infection occurred. Both virulent viruses caused astrocytic syncytial formation but did not cause cytolysis of the astrocyte population as was observed with the attenuated virus. Titers of infectious virus, released into the supernatant fluid, reflected the degree of astrocyte infection. Virus released by the cultures late in CDV A75-17 infection showed enhanced ability to infect newly derived astrocytes; in contrast, brain cell passaged CDV-SH did not show increased growth in these cells. These results show that (1) there is a difference in growth rate, CPE and capacity for adaptation of three different CDV strains in astrocytes in vitro, and (2) some aspects of the disease (such as persistence in white matter) produced by the virulent strains in vivo may be related to the course of astrocyte infection observed in vitro. PMID- 2333035 TI - Long-term effects of Org OD 14 on lipid metabolism in post-menopausal women. AB - The effects of 2.5 mg/day 7 alpha, 17 alpha-17-hydroxy-7-methyl-19-norpregn-5(10) en-20-yn-3-one (Org OD 14) on lipid metabolism, with particular reference to high density lipoprotein (HDL)-related variables, were assessed in 14 healthy post menopausal women after 12 and 36 mth of treatment. There were significant reductions in the following variables after both treatment periods: total phospholipids, total triglycerides, HDL-phospholipids and apolipoprotein A1. No changes were observed in total cholesterol or low-density lipoprotein (LDL) cholesterol over the entire treatment period. A significant but temporary decrease was observed in HDL-cholesterol after 12 mth, with a return to pretreatment values after 36 mth of treatment. The findings of this study clearly show that Org OD 14 has no adverse effects on the atherogenic variables, viz. LDL cholesterol and triglycerides. Indeed, since the latter were lowered, its action is in fact beneficial. Moreover, its effect on HDL-cholesterol, the anti atherogenic variable, is only temporary. We concluded from this study that although the composition of HDL changes during Org OD 14 treatment (especially as regards its cholesterol content), there is no evidence that reverse cholesterol transport is impaired. PMID- 2333036 TI - Age of menopause in Japanese women: trends and recent changes. AB - The age of menopause was investigated in a survey conducted in 1987 in 13,996 Japanese women aged 22-86 years, the findings being as follows: (1) The percentage of post-menopausal women showed a sharp linear increase between the ages of 49 and 53 years, the figure being 42.7% at age 50. The rate of increase was slightly lower after 50 years of age. (2) Among the 6477 post-menopausal women, the age at which the peak number had undergone menopause was 50 years (17.7%), followed by 49, 52 and 48 years. The crude mean age of menopause was 49.33 years in post-menopausal subjects aged over 40. The mean age of menopause in urban and rural women was not significantly different. (3) The crude mean age of menopause, calculated by classifying those aged 50 (born in or before 1937) into groups corresponding to 5-year age intervals, was highest in the 1928-32 birth-year group, followed, in descending order, by the 1923-27, 1918-22, 1917 or earlier and 1933-37 groups in all post-menopausal and in urban subjects, while in rural subjects it was highest in the 1918-22 group. However, overall, the adjusted mean age of menopause was highest (50.2 +/- 3.24 years) in the 1928-32 birth-year group, followed by the 1923-27 and 1933-37 groups. PMID- 2333037 TI - An epidemiological study of urinary incontinence and related urogenital symptoms in elderly women. AB - The prevalence of urinary incontinence (UI) and related urogenital symptoms (UGS) was investigated in a random sample (n = 4206) of women from the 1900-20 birth cohorts residing in the city of Goteborg. It was reported by 16.9% of the respondents that they currently had UI and by 22.7% that they had regularly suffered from this complaint at some time in their lives. The prevalence of UI increased (P less than 0.001) with rising age, from 13.9% in the 1920 birth cohort to 24.6% in the 1900 birth cohort. Over 50% of the sufferers reported daily incontinence. An objective assessment was performed in a subsample (n = 300) of the women complaining of UI. In 14 cases (4.6%) the diagnosis could not be confirmed, while in the remainder UI was classified by type as follows: stress incontinence 24%, urge incontinence 49% and mixed incontinence 27%. The number of urinary tract infections (UTI) reported by the respondents increased (P less than 0.001) with rising age. UGS such as pruritus, burning, pain and vaginal discharge were reported by 11% of the respondents. The reported frequency of local vaginal discomfort did not increase with age, unlike that of UI and UTI. Systemic or local oestrogen treatment was being received by 9.2% of the respondents. PMID- 2333038 TI - Urodynamic evaluation prior to total hysterectomy: indications and incidence of abnormality. AB - Although it is recognized that total hysterectomy may be associated with subsequent urinary symptoms, many women are symptomatic prior to operation. However, only objective rather than subjective analysis can provide an accurate assessment of the preoperative state of the lower urinary tract. This study determined the incidence of preoperative, urodynamically-proven, vesicourethral dysfunction in women undergoing total hysterectomy. The incidence of urinary symptoms in 30 women awaiting hysterectomy was assessed and compared with the urodynamic findings. Sixteen (53%) of these patients had preoperative urinary symptoms, although bladder dysfunction was present in only 8 (27%). The presence of marked urinary symptoms in women awaiting hysterectomy warrants preoperative urodynamic investigation to identify any underlying bladder dysfunction. PMID- 2333039 TI - Adjuvant chemotherapy of early breast cancer. PMID- 2333040 TI - Characterization of fragmented heavy-ion beams using a three-stage telescope detector: measurements of 670-MeV/amu 20Ne beams. AB - Measurements of a 670-MeV/amu 20Ne beam at the Lawrence Berkeley Laboratory Bevalac heavy-ion accelerator with various thicknesses of water absorber were obtained with the BERKLET. The BERKLET, a simple three-stage solid-state telescope detector, has been described previously. This instrument measures the linear energy transfer (LET) and residual energy of particles, allows the identification of the particle's charge, and provides a means of obtaining LET and energy statistics for the beam, separated by particle charge. The track and dose averaged LET dependence on the amount of water absorber was determined for each species of fragment in the beam. Large numbers of low-LET particles in the fragmented beam were detected. The results of the analysis are presented followed by a discussion of the effects of multiple scattering and secondary fragmentation on the measurements. A brief discussion of the implications of the BERKLET measurements for radiobiology is also presented. PMID- 2333041 TI - Characterization of fragmented heavy-ion beams using a three-stage telescope detector: detector configuration and instrumentation. AB - Accelerated heavy-ion beams used in biological and medical research are often utilized in conjunction with absorbers which lead to the fragmentation of the beam. The BERKLET, initially a two-stage solid-state telescope detector, was designed to make rapid, on-line energy and linear energy transfer (LET) measurements of individual particles in a heavy-ion beam, thus allowing characterization of fragmented beams. From data collected with the BERKLET, one is able to determine a number of important parameters. These include: residual energy and LET histograms for the full beam and for the individual Z components, relative number of particles with a given Z, and dose and track average LET's for the full beam and for the individual Z's. Improvements to the BERKLET design and changes in data analysis are discussed and contrasted with the results of an earlier BERKLET configuration. The most notable improvements are the addition of a thin scintillation detector for improved LET measurement, a tenfold improvement in the dynamic range of the event discriminator, reported here as 1:2000, and dual high-and low-gain amplification of the LET signals, permitting the identification of particles with Z's ranging from 12 down to 1. PMID- 2333042 TI - The multiple Coulomb scattering of very heavy charged particles. AB - An experiment was performed at the Lawrence Berkeley Laboratory BEVALAC to measure the multiple Coulomb scattering of 650-MeV/A uranium nuclei in 0.19 radiation lengths of a Cu target. Differential distributions in the projected multiple scattering angle were measured in the vertical and horizontal planes using silicon position-sensitive detectors to determine particle trajectories before and after target scattering. The results were compared with the multiple Coulomb scattering theories of Fermi and Moliere, and with a modification of the Fermi theory, using a Monte Carlo simulation. These theories were in excellent agreement with experiment at the 2 sigma level. The best quantitative agreement is obtained with the Gaussian distribution predicted by the modified Fermi theory. PMID- 2333043 TI - Effects of gold and silver backings on the dose rate around an 125I seed. AB - Measurements of the effect of either gold or silver backing on the dose rate around an 125I seed were performed using a Therados RFA7 dosimetry system and a small diode detector which was 2.5 mm in diameter and 0.06 mm thick. It was found that the presence of the gold or silver backing modifies the diode response on the side of the 125I seed away from the backing. The effect depends on the backing material and the distance from the seed. There is a small increase close to the gold backing but a decrease further away. This decrease at distances greater than 10 mm from the seed is uniformly 10%, the same as found when the seed is backed by air. There is an increase of up to 25% observed with silver backing the seed and this increase remains significant more than 30 mm from the seed. When the response increases, the results are hard to interpret quantitatively because of variations in the diode response per unit dose with photon energy and extreme sensitivity to geometric changes. Nonetheless, except for the increase at close distances with the gold, the results are in agreement with EGS4 Monte Carlo photon transport simulations which are for a simplified geometry and account for x-ray fluorescence from the K-shell. Furthermore, the increase in the gold-backed case is qualitatively explained by Williamson's Monte Carlo calculations which take into account the L-shell fluorescent x-rays from gold. PMID- 2333044 TI - EGS4 Monte Carlo determination of the beta dose kernel in water. AB - The EGS4 Monte Carlo code has been used to simulate the emission and energy deposition in H2O about point sources of monoenergetic electrons and radionuclides of potential use in radioimmunotherapy. The radiations studied were 0.05, 0.1, 0.5, 1.0, 2.0, and 3.0 MeV monoenergetic electrons and 32P, 67Cu, 90Y, 105Rh, 131I, 153Sm, 186Re, and 188Re beta particles and conversion and Auger electrons. Ten batches of 10,000 electrons (or 10,000 radionuclide decays) each were started isotropically at a point in an infinite homogeneous H2O phantom. The parameter-reduced electron-step transport algorithm (PRESTA) version of the EGS4 Monte Carlo code was used to follow these and their progeny, scoring the energy deposited in thin spherical shells. The scaled dose kernels are calculated and compared to kernels available in the literature. These previously published kernels either completely ignore secondary electrons or are based on a Monte Carlo code which improperly sampled the Landau energy straggling distribution. PMID- 2333045 TI - The validity of the density scaling method in primary electron transport for photon and electron beams. AB - In the convolution/superposition method of photon beam dose calculations, inhomogeneities are usually handled by using some form of scaling involving the relative electron densities of the inhomogeneities. In this paper the accuracy of density scaling as applied to primary electrons generated in photon interactions is examined. Monte Carlo calculations are compared with density scaling calculations for air and cork slab inhomogeneities. For individual primary photon kernels as well as for photon interactions restricted to a thin layer, the results can differ significantly, by up to 50%, between the two calculations. However, for realistic photon beams where interactions occur throughout the whole irradiated volume, the discrepancies are much less severe. The discrepancies for the kernel calculation are attributed to the scattering characteristics of the electrons and the consequent oversimplified modeling used in the density scaling method. A technique called the kernel integration technique is developed to analyze the general effects of air and cork inhomogeneities. It is shown that the discrepancies become significant only under rather extreme conditions, such as immediately beyond the surface after a large air gap. In electron beams all the primary electrons originate from the surface of the phantom and the errors caused by simple density scaling can be much more significant. Various aspects relating to the accuracy of density scaling for air and cork slab inhomogeneities are discussed. PMID- 2333046 TI - Calculation of three-dimensional photon primary absorbed dose using forward and backward spread dose-distribution functions. AB - This paper describes a method of calculating three-dimensional (3-D) photon primary absorbed dose in a homogeneous or heterogeneous medium. The method is based on a technique of convolving a pair of forward and backward spread dose distribution functions with the primary water collision kerma distribution. Both spread dose-distribution functions can be constructed by analyzing the zero-area tissue-maximum ratio, the primary absorbed dose near the beam exit surface, and the laterally spread dose distribution. Primary absorbed dose calculations are performed along the beam axis for 10-MV x rays. The characteristic patterns of primary dose in heterogeneous phantoms containing an aluminum or lunglike material slab can be obtained. PMID- 2333047 TI - 10-MV x-ray primary and scatter dose calculation using convolutions. AB - Three-dimensional (3-D) forward and backward primary dose spread functions in water were developed for 10-MV x rays. Three-dimensional forward and backward primary dose spread functions in a heterogeneous medium were constructed from the ones in water using the density scaling theorem. Each of the forward and backward primary dose components were calculated using a method of convolving the primary water collision kerma distribution with the forward or backward primary dose spread function. Scatter dose was separated into forward and backward components. Each scatter dose component was calculated using a differential scatter method, a kind of convolution method, where the primary water collision kerma distribution was convolved with a differential scatter-maximum ratio or differential backscatter factor equation. From the dose calculation and measurement results obtained for water phantoms containing a cork or aluminum slab, it was found that the 3-D forward and backward primary dose functions were effective especially in regions where there was a loss of longitudinal and/or lateral electronic equilibrium. PMID- 2333048 TI - A study of quality of bremsstrahlung spectra reconstructed from transmission measurements. AB - A numerical method for the reconstruction of bremsstrahlung spectra has been applied to the analysis of simulated data. The method is found to be reliable in reconstructing x-ray spectra of maximum energy up to 10 MeV. Measurements of aluminum transmission data carried out for five linear accelerators have also been analyzed by this method to determine the fractional energy fluence. The values of the Spencer-Attix water/air stopping power ratio, SS.A. w,air, reported as a function of the ratios TPR20 10, are in good agreement with computed results. Quality index values were correlated to mean incident energies of x-ray beams used in radiotherapy. The experimental setup has also provided information regarding the softening effect on the off-axis beam, which can be used in clinical computer dosimetry to correct conventional zero field size tissue maximum ratio. PMID- 2333049 TI - Neural networks in radiology: an introduction and evaluation in a signal detection task. AB - Neural networks are a computer architecture, implementable in software or hardware, that allow an entirely new approach to the computerized perception of data. These so-called connectionist models are inspired by what is known about the architecture of biological neurons, in which the "intelligence" or processing capability of the network is a result of the interconnection strengths between large arrays of nonlinear processing nodes. Neural networks are described and then are used to analyze the common radiological problem of pattern recognition on a noisy background. Classical signal detection theory is used to compare network performance against that of human observers, using computer-generated sets of very simple "nodules." The neural network performed with better accuracy, relative to human observer performance, in the detection of this elementary test object. Although these results may not scale up with more complex images, the favorable performance of neural networks at this level suggests that further investigation is warranted. PMID- 2333050 TI - Effects of x-ray beam equalization on mammographic imaging. AB - We employed an elastic reservoir filled with tissue-equivalent fluid as an x-ray beam filter for exposure equalization. The filter is designed to be placed between the upper compression plate and the breast. During compression, it will conform to the shape of the peripheral region of the breast and fill the space between the upper and lower compression plates, thereby reducing the variation in x-ray penetration between the thick and thin regions of the breast and compressing the dynamic range of the breast image. Results of a phantom study showed that the visibility of low-contrast features was improved in the peripheral region of the equalized breast phantom image. Experimental measurements indicated that the filter reduced scattered radiation in the peripheral region. This result was confirmed by a Monte Carlo simulation study. The radiation contrast, with the effect of beam hardening included, was also improved when equalization was employed. PMID- 2333051 TI - Signal-to-noise efficiency in magnetic resonance imaging. AB - The dependence of signal-to-noise ratio (SNR) on the analog filter, the sampling rate and the number and dimensions of voxels is derived for magnetic resonance imaging (MRI). It is shown that the object signal-to-noise ratio scales directly with the voxel volume and the square root of the number of voxels. Defining an efficiency figure of merit as the SNR divided by the square root of the imaging time, it is shown that efficiency is always improved when imaging with the lowest possible resolution (largest voxel dimensions) consistent with viewing the desired anatomical detail. The results directly imply the relative efficiency of 3-D (volume), 2-D (plane), 1-D (line) and 0-D (point) imaging techniques. It is shown that spatial averaging is an inefficient method of noise reduction in MRI. As long as voxel size is maintained constant, one can image as many pixels in the readout direction as desired with no loss in SNR; that is, the number of pixels in the readout direction has no effect on the image SNR. Further, multiple sampling of each phase encoding value (to improve SNR) has no advantage over increasing the number of pixels in the phase encoding direction while leaving the voxel size constant. Some experimental observations are given. PMID- 2333052 TI - A magnetic resonance imaging method of flow by successive excitation of a moving slice. AB - A new magnetic resonance imaging of flow by a method of successive excitation of a moving slice is presented here. The method, which in general belongs to the class of time-of-flight methods, is based upon selectively changing the frequencies in a sequence of rf pulses in such a way that a selected slice moves through the imaged volume in a preselected direction and velocity, and is repeatedly excited. It is claimed that most of the measured signal is contributed by only those parts of the imaged substance that move with the selected slice. The activation procedure of the flowing spins, which is presented here, enhances the imaging of the flowing matter and reduces the signal from static matter. A specially tailored selective sequence of a rf alpha-pulses has been developed. During this sequence, a set of rephasing 180 degrees selective rf pulses is applied. At the end of this sequence an additional 180 degrees rf pulse is applied to eliminate redundant signals from the static matter in the last activated slice. PMID- 2333053 TI - Estimation of geometrical parameters and collimator evaluation for cone beam tomography. AB - A method is presented for estimating the geometrical parameters for a cone beam detector geometry from the coordinates of the centroid of a projected point source sampled over 360 degrees. Nonlinear expressions are derived for the coordinates of the centroids in terms of the geometrical parameters which include: the two-dimensional coordinates of the projection of the center of rotation onto the detector image plane; the focal length; the distance from the focal point to the center of rotation; and the spatial coordinates of the point source itself. Experimental data were obtained using a rotating gamma camera with a symmetrically converging collimator. The Marquardt algorithm was used to estimate the parameters for this particular cone beam geometry. The method was able to estimate the geometrical parameters and evaluate the accuracy of the collimator construction. PMID- 2333054 TI - Development of an anthropomorphic breast phantom. AB - A new technique for producing anthropomorphic radiologic phantoms is described. Information from a patient radiograph is used to design the phantom. Optical densities from a digitized radiograph are converted to thicknesses of a phantom material, with corrections for geometry, x-ray spectrum, and scatter. Numerically controlled machining techniques are used to transcribe the anatomic details into the phantom material. High spatial frequencies are reproduced separately from low spatial frequencies using photochemical techniques in order to replicate finer details in the phantom. The result is a phantom consisting of a number of overlays. Radiographs of a breast phantom produced using the technique are shown, energy equivalence to attenuation of breast tissue is assessed, and methods of incorporating fine detail and quantitative features in the phantom are suggested. PMID- 2333055 TI - Quality assurance methods and phantoms for magnetic resonance imaging: report of AAPM nuclear magnetic resonance Task Group No. 1. PMID- 2333056 TI - Basic theory, design, and preliminary evaluation of a laser scanner for shape sensing below-the-knee amputees. AB - A scanner which produces surface profiles of residual limbs from below-the-knee amputees was constructed and evaluated. The scanner uses a turntable mounted laser to define a surface profile line, a charge-coupled-device video camera to view the profile, and a custom designed video processing board to extract profile data. A microcomputer is used to control data acquisition and provides the rapid processing capability necessary to resolve scan profile data into a three dimensional numerical description of the surface in a timely and cost effective manner. Flexibility of use as well as positional accuracy and reproducibility indicate that the laser scanner is well suited to the task of surface scanning of residual limbs for below-the-knee amputees. Additionally, the laser profile scanning technique can be applied to other regions of the body where a mathematical description of the surface is useful, such as in radiotherapy treatment planning. PMID- 2333057 TI - Acceptance testing of an automated scanning water phantom. AB - The setup of an automated scanning water phantom must be concluded with a methodical functional acceptance test. This test must include mechanical, radiological, and calculational facets. Only after an acceptance test is successfully completed can data collected with a new or repaired system be trusted. An acceptance test outline was written and applied to a newly purchased Wellhofer scanning system. This testing procedure and its results are presented in this paper. PMID- 2333058 TI - Use of the AAPM (American Association of Physicists in Medicine) standard for digital image interchange in nuclear medicine. PMID- 2333059 TI - [New aspects of the mechanism of action of molsidomine. Proceedings of a discussion by cardiology experts. Berlin, 15 April 1989]. PMID- 2333060 TI - [1st Symposium on Adolescence. Turin, 26 November 1988. Proceedings]. PMID- 2333061 TI - Compensatory tracking in humans with elevated carboxyhemoglobin. AB - A total of seventy-four men divided into five groups performed a compensatory tracking task for 4 hr with group mean carboxyhemoglobin (COHb) levels of 0.9, 5.6, 6.1, 11.4 or 16.6%. In all but one group, COHb was formed in approximately 5 min by having the subject breathe a high concentration of carbon monoxide (CO) from a Douglas bag. An appropriate low level of CO in the exposure/test chamber maintained the elevated COHb for the 4-hr duration of the experiment. A slow COHb formation group, not exposed to CO during bag breathing, which was only exposed to low-level CO in the exposure/testing chamber, served as a positive control. Even though mean tracking error scores increased in a nearly monotone manner as a function of COHb, the effects were not statistically significant. Even at the highest dose, the increase in tracking error was small. The increased mean error score due to rapid formation was virtually the same as that due to slow formation. PMID- 2333062 TI - Toluene and benzene inhalation influences on ventricular arrhythmias in the rat. AB - We have previously found that toluene did not share the capacity of benzene for increasing the arrhythmogenic action of epinephrine in the rat, but appeared to elicit the opposite effect. The present experiments were carried out to verify this observation in rats subjected to more severe ventricular arrhythmias. In animals previously inhaling either air, toluene or benzene and anesthetized with pentobarbital, arrhythmias were produced by coronary ligation or aconitine. In both models, toluene decreased and benzene increased the number of ectopic ventricular beats in the 30 min following induction of arrhythmia. Gas chromatographic measurement of toluene levels in the heart during and after inhalation revealed essentially constant concentrations at the time of arrhythmia evaluation, equivalent to approximately one-third the peak levels observed at the end of inhalation. Although the mechanism of the effect of toluene on arrhythmia could not be ascertained, nonspecific membrane stabilization or central serotonergic stimulation were considered as possible explanations. Since both mechanisms could be operant also in the case of benzene, the opposite effects of the solvents on arrhythmia could not be readily accounted for. PMID- 2333063 TI - Behavioral effects of subchronic intoxication with parathion-methyl in male Wistar rats. AB - The behavioral effects of subchronic exposure of male Wistar rats to the organophosphorus compound parathion-methyl (for 6 weeks 1/50 or 1/100 of LD50, PO) were studied. Open-field (OF) and elevated plus-maze (EPM) tasks were used to decide whether or not the compound can affect behavior. Significant effects were measured in the OF activity during the first minute, on the activity of crossing outer squares, increasing latencies to leave center, start of rearing, grooming, and defecation. EPM parameters showed an increased amount of time spent in the open arms and a clear tendency to enter more frequently open arms. The defecation rate in the EPM was significantly decreased. Results are discussed in terms of effects on emotional behavioral components (arousal) and on physiological functioning of the peripheral nervous system (lengthening of latencies). PMID- 2333064 TI - Discriminative stimulus properties of toluene in the rat. AB - Rats were trained to discriminate toluene (100 mg/kg, IP) from vehicle in a two lever operant task. Acquisition of the discrimination required a range of 85-219 training days. Injections of either methohexital (0.5-10 mg/kg) or oxazepam (0.5 20 mg/kg) produced toluene-lever responding in a dose-dependent fashion in most animals. The discriminative stimulus properties of toluene were not found to generalize to chlorpromazine (0.3-10 mg/kg). These results are consistent with those obtained in the mouse and provide further evidence that toluene has stimulus properties similar to those of CNS depressant drugs. These results further suggest that toluene may have drug abuse potential of the CNS depressant type. PMID- 2333065 TI - Passive avoidance performance following neonatal alcohol exposure. AB - Prenatal alcohol exposure has been associated with deficits in response inhibition in both human and nonhuman studies. In this study, we investigated the effects of neonatal alcohol exposure on passive avoidance, a task that requires response inhibition. Neonatal alcohol exposure has been used to examine the effects of alcohol during a period of CNS development that is equivalent to the human third trimester "brain growth spurt." Subjects were 23-day-old rats that were artificially reared (AR) from gestation day (GD) 26-32 through gastrostomy tubes. The AR groups included two ethanol doses; 6 g/kg and 4 g/kg and an isocaloric control. A sham surgery group was also included. Subjects were tested for acquisition and 24-hr retention of the passive avoidance task. The 6 g/kg females required more trials to reach the criterion during both acquisition and retention relative to all other groups. These findings suggest that neonatal alcohol exposure can produce deficits in response inhibiton, but that there may be differential sensitivity across sexes to some of alcohol's effects. PMID- 2333066 TI - Neurotoxic behavioral effects of Lake Ontario salmon diets in rats. AB - Six experiments were conducted to examine possible neurotoxic effects of the exposure to contaminants in Lake Ontario salmon administered through the diets of rats. Rats were fed different concentrations of fish (8%, 15% or 30%) in one of three diet conditions: Lake Ontario salmon, Pacific Ocean salmon, or laboratory rat chow only. Following 20 days on the diets, rats were tested for five minutes per day in a modified open field for one or three days. Lake Ontario salmon diets consistently produced significantly lower activity, rearing, and nosepoke behaviors in comparison with ocean salmon or rat chow diet conditions. A dose response effect for concentration of lake salmon was obtained, and the attenuation effect occurred in males, females, adult or young animals, and postweaning females, with fish sampled over a five-year period. While only two of several potential contaminants were tested, both fish and brain analyses of mirex and PCBs relate to the behavioral effects. PMID- 2333067 TI - Dose-response effects of prenatal phenytoin exposure in rats: effects on early locomotion, maze learning, and memory as a function of phenytoin-induced circling behavior. AB - Pregnant Sprague-Dawley CD rats were administered 0, 100, or 200 mg/kg of phenytoin on days E7-18. Litters were reduced to 12, balancing for sex. Mean (+/- S.E.) maternal serum concentrations of total phenytoin 1 hr after dosing on E18 were 15.1 +/- 3.1 and 20.9 +/- 4.3 micrograms/ml in the PHT-100 and PHT-200 groups, respectively. Determinations of unbound concentrations revealed the drug to be 89% serum protein bound in both phenytoin groups. Maternal phenytoin concentrations in rats are, therefore, comparable to those seen therapeutically in humans with epilepsy. The PHT-200 group had elevated early postnatal mortality, while the PHT-100 group did not differ from controls. Phenytoin induced the typical dose-dependent increase in preweaning square-field locomotor activity. When this effect was compared to a new circular open field it was found that this device clearly distinguished phenytoin's effects. Phenytoin offspring also showed the typical dose-dependent abnormal circling behavior. Phenytoin offspring exhibited large dose-dependent increases in errors in a complex water maze, an effect which persisted even when rats exhibiting abnormal circling were excluded from the analyses. Offspring were also assessed for ability to locate a hidden vs. visible platform in an open swimming tank. Controls and PHT-100 offspring showed large improvements in performance when the hidden platform was made visible, but the PHT-200 offspring did not. Finally, offspring were assessed for working memory in an appetitive radial-arm maze. Both phenytoin groups exhibited impaired performance as measured by the number of reinforcements obtained in the first 8 arms visited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333068 TI - ZPT-related distal axonopathy: behavioral and electrophysiologic correlates in rats. AB - These experiments examined the relationship between behavioral and electrophysiologic signs of neuromuscular dysfunction in rats with zinc pyridinethione (ZPT)-induced neurotoxicity. ZPT added to the diet of adult rats at 50 ppm produced a moderate (approximately 200 g) reduction in forelimb and hindlimb grip strength which occurred during the second week of dosing. Other behavioral tests of peripheral nervous system toxicity were affected inconsistently. Electrophysiologic changes included a marked (maximum 95%) reduction of indirect muscle-evoked potential (M-wave) and a decrement (maximum 30%) during repetitive M-wave elicitation. Electrophysiologic changes were greater in hindlimb than in forelimb. Needle electromyography revealed denervation potentials in ZPT-treated rats which appeared after M-wave changes and recovered faster than did M-wave amplitude. Caudal nerve conduction velocity was unaffected, indicating that peripheral neurotoxic effects were confined to the neuromuscular junction. When ZPT exposure was discontinued, grip strength recovered in about 1 week. In contrast, electrophysiologic measures required 42 days to recover completely. These results indicate that deficits in neuromuscular junction physiology are a sensitive index of ZPT-related distal axonopathy. PMID- 2333069 TI - Maternal marijuana use during lactation and infant development at one year. AB - Prenatal marijuana exposure is associated with adverse perinatal effects. Very little is known about the effect of postnatal marijuana exposure on infant development. Postnatal exposure can result from maternal use of marijuana during lactation. Delta-9-tetrahydrocannabinol (THC) transfers and concentrates in the mother's milk and is absorbed and metabolized by the nursing infant. The present study investigated the relationship between infant exposure to marijuana via the mother's milk and infant motor and mental development at one year of age. One hundred and thirty-six breast-fed infants were assessed at one year of age for motor and mental development. Sixty-eight infants were exposed to marijuana via the mother's milk. An additional 68 infants were matched to the marijuana-exposed infants on pre- and postpartum maternal alcohol and tobacco use. Marijuana exposure via the mother's milk during the first month postpartum appeared to be associated with a decrease in infant motor development at one year of age. PMID- 2333070 TI - Behavioral deficits due to prenatal exposure to cadmium chloride in CFY rat pups. AB - The postnatal behavioral effects of 0.20, 0.62 and 2.0 mg/kg cadmium chloride administered to pregnant CFY rats on gestational days 7 through 15 were evaluated. Offspring were tested starting on postnatal day 23 on a rotorod for motor coordination, in an open field device for motor activity and emotionality, in a water-filled tube for stress responses, in the acquisition and extinction of an instrumental shock-escape response and in a social interaction situation. All behavioral measures showed significant alterations at the medium and high dose of cadmium exposure. The results suggest that doses of cadmium chloride that produce no overt toxicity in the dam can have long-lasting behavioral alterations in the offspring. PMID- 2333071 TI - Apomorphine-induced motor behavior in rats exposed prenatally to alcohol. AB - We psychopharmacologically examined dopamine function in rats exposed to ethanol prenatally. Pregnant rats received liquid diets of 35% or 0% ethanol-derived calories (EDC), or ad lib lab chow (LC). Twenty-eight-day-old offspring received systemic doses of apomorphine chosen to stimulate predominantly presynaptic (0.02 or 0.1 mg/kg) or postsynaptic dopamine receptors (2.0 or 5.0 mg/kg). Behavior was scored automatically for 60 min in an "open field." For males, prenatal ethanol exposure resulted in a dose-response shift to the left for locomotor activity. Females exposed to the liquid diet, with or without ethanol, showed less of an increase in locomotor activity following the 5.0 mg/kg dose of apomorphine than did LC controls. There were no effects of prenatal treatment on repetitious motor behavior in the automated "open field" or on stereotypy scored by direct observation in separate groups of rats. The results are consistent with an hypothesis that prenatal ethanol exposure alters the sensitivity of postsynaptic (perhaps mesolimbic) dopamine systems important to locomotor activity in young male rats. PMID- 2333072 TI - Secalonic acid D mycotoxin affects ontogeny of brain catecholamines and swimming in mice. AB - Suckling mice exposed to secalonic acid D (SAD) mycotoxin postnatally (by gavaging dams with 0, 15 or 25 mg/kg on postgestational days 1 to 10) or prenatally (by gavaging with 25 mg/kg on gestational day 13 to produce a positive behavioral teratogenic control group) manifested subtle preweaning neurobehavioral, neurochemical and growth deficits. Gestational length, maternal weight gain, neonatal sex ratio and physical appearance of pups at birth were unaffected by treatment. Prenatal SAD (25 mg/kg) delayed (p less than 0.05) ontogeny of swimming on postnatal days (PND) 11 and 13 and reduced norepinephrine (NE) and dopamine (DA) levels in prosencephalon on PND 7 and in cerebellum-pons on PND 7-16. In the postnatal treatment groups, pup body weight gains were decreased from PND 9-22. Swimming was delayed in the 15 mg/kg postnatal exposure group on PND 11 and 13, while 25 mg/kg delayed swimming on PND 11-15. Postnatal exposure to 25 mg/kg also reduced NE and DA levels in prosencephalon and cerebellum-pons on PND 7-16. SAD thus caused concomitant ontogenetic delays in growth, swimming behavior and brain catecholamine levels following either prenatal (transplacental) or early postnatal (transmammary) exposure. These data indicate that both in utero and lactational exposures must be considered when assessing potential risks posed to developing mammals by environmental neurotoxicants. PMID- 2333073 TI - Effects of postnatal lead exposure on open field behavior in monkeys. AB - Nursery-reared rhesus monkeys were treated with either no lead or moderate levels of lead from day eight or nine until day 365 after birth. All subjects were at or below 5 micrograms/dl blood lead levels for at least 1.5 years by the time of the present study conducted at 4 years of age. Data were collected in a primate version of the open field test which proved sensitive to several behavioral alterations in the lead-treated monkeys. These significant differences included a failure to habituate as evidenced by number of sectors entered, increased durations of activity and environmental exploration, and a longer latency to enter the open field. Most of these effects were compatible with a hypothesis of hippocampal dysfunction in the lead-treated monkeys and appeared to indicate enduring lead-induced alterations. These results provide further support for a correlation between early lead exposure and hippocampal dysfunction. Additionally, the utility of a primate version of the open field test for behavioral toxicological studies is substantiated. PMID- 2333074 TI - Behavioral antagonism between lead and cadmium. AB - Adult male rats were exposed to one of four dietary conditions for a period of 60 days. Group Control-Diet received a diet containing no added lead or cadmium, group Lead-Diet received a diet that contained 500 ppm added lead, group Cadmium Diet received a diet that contained 100 ppm added cadmium, and group Lead-Cadmium Diet received a diet that contained both 500 ppm added lead and 100 ppm added cadmium. Subsequent to exposure, animals were tested in a Digiscan activity monitor. Animals were then sacrificed and metal concentrations were determined in blood and brain. The results from this experiment showed that lead alone increased movement and vertical activity. Cadmium alone decreased movement and increased rest time. Cotreatment with lead and cadmium failed to produce behavioral differences relative to controls; thus, it seems that the changes in activity caused by one metal are antagonized by the other. Results from the analyses of residues in tissues revealed that blood lead concentrations were lower in the cotreatment condition than the lead along condition. However, brain residue accumulations were not different for these two exposure conditions. There was no evidence that the presence of lead attenuated increases in cadmium residues in blood or brain. Overall, the residue data agree with a central, as contrasted with a peripheral, account of lead/cadmium interaction effects, at least as relates to behavior. Because lead and cadmium were additive with regard to producing decreased body weights, it seems that the toxic effect of these metals is antagonized by cotreatment in some instances, and augmented in others. PMID- 2333075 TI - Acquired immunodeficiency syndrome and malnutrition: role of gastrointestinal pathology. PMID- 2333076 TI - Standards of practice for nutrition support dietitians. American Society for Parenteral and Enteral Nutrition. PMID- 2333077 TI - [Functional properties of the pOV13 plasmid as a vector for DNA cloning in a broad spectrum of gram negative bacteria]. AB - The birepliconed plasmid pOV13 possesses all the properties of a vector for DNA cloning in a broad host range of bacterial cells. pOV13 is transfered by transformation and stably inherited by Escherichia coli, Brucella, Pseudomonas cells determining the resistance to streptomycin, tetrocycline and kanamycin in these bacteria. The plasmid pOV13 is a multicopy plasmid optimal in replication capacity (23kb). The plasmid carries single sites for some restriction endonucleases that are used for DNA cloning, including some restriction sites in antibiotic resistance genes. The examples of DNA cloning with the selection of recombinant clones by the insertional inactivation of kanamycin or tetracycline resistance and expression of the cloned DNAs are presented. PMID- 2333078 TI - [Express diagnosis of hereditary hemoglobinopathies in newborn infants]. AB - An improved version of the method for electrofocusing of the globin chains extracted from the dried blood dots of newborn on the ultrathin polyacrylamide ampholine gels at pH 5-8 is described. The method permits clinical diagnosing of hereditary hemoglobinopathies of the newborn. PMID- 2333080 TI - [Plasmids of Yersinia pseudotuberculosis]. AB - Plasmids with the sizes of 5.7; 51; 70-77; and 120-130 kb were found in six strains among the ten strains collection of Yersinia pseudotuberculosis. The restriction endonucleases analysis. Southern-blot hybridization and physical maps construction were performed for the plasmids. The 70-77 kb plasmids were found to be analogous to the Ca2(+)-dependence plasmid pYVO19 from Yersinia pestis EV76. The difference between the plasmids of this type is in the insertions or deletions located on the similar fragments of the restriction maps. The 51 kb plasmid has no common fragments with the Ca2(+)-dependence plasmids and does not code for virulence properties of the strain harbouring it. No homology is shared by the 5.7 kb plasmid and the 10 kb plasmid from Yersinia pestis EV76. Replicon of the 5.7 kb plasmid has been used to construct the pVS11 vector plasmid. PMID- 2333079 TI - [Tick-borne encephalitis virus: primary structure of DNA copies of the genes for strain 205 structural proteins]. AB - The nucleotide sequences of the cDNAs of the genes for the structural proteins C, preM, M and E of the tick-borne encephalitis viral strain 205 have been determined. The complete nucleotide sequence of the 5'-end nonstructural region of the viral genome has been studied for the first time. The difference in the amino acids sequences of the structural proteins from different strains (205, Sofiin and Neidorf) of the virus is discussed. PMID- 2333081 TI - Induction of micronuclei in Vicia faba root tips treated in different soils with the herbicide alachlor. AB - A study was made of the clastogenic effect of the herbicide alachlor using the micronucleus test on root tips of seeds of Vicia faba that had been placed in 2 soils with different characteristics. No significant increase in micronuclei was observed in the seeds planted in the soil with a high content of organic matter. In those planted in soil with a low content, an increase in micronuclei proportional to dose and exposure time was observed. HPLC analysis of the alachlor residues in the 2 soils showed that they have a different capacity for absorbing the herbicide, which would account for the different genotoxic responses observed. PMID- 2333082 TI - Chromosomal aberrations and sister-chromatid exchanges in lymphocytes of workers exposed to sulphur dioxide. AB - The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCE) in peripheral blood lymphocytes of 40 workers chronically exposed to sulphur dioxide (SO2) at a sulphuric acid factory in Taiyuan City (North China), were studied. It was shown that the mean frequency of chromosomal aberrations and the mean frequency of lymphocytes with chromosomal aberrations of the SO2-exposed workers were both higher than the controls. The mean per 1000 metaphase frequencies of severe chromosomal aberration types (chromosome rings, translocations, and dicentrics) of the workers and the controls were 9.63 and 2.27, respectively. The difference between them was statistically significant (p less than 0.01). It was also shown that the mean SCEs/cell of SO2-exposed workers and non-exposed controls were 6.72 +/- 0.22/cell and 2.71 +/- 0.13/cell (p less than 0.01) respectively. SCEs/cell in 39 workers were all higher than 5, only 1 worker was 4.73. However, 41 controls were all lower than 4, only 1 control was 4.92. The difference between the worker and the control group was statistically significant. These results show that SO2 is a clastogenic and genotoxic agent. No positive correlation between the frequencies of chromosomal aberrations or SCE and length of service in the workers has been observed. No significant difference between smokers and non-smokers was found in these assays. PMID- 2333083 TI - Prediction of carcinogenic potency from toxicological data. PMID- 2333084 TI - A comparison of DNA adduct formation in white blood cells and internal organs of mice exposed to benzo[a]pyrene, dibenzo[c,g]carbazole, safrole and cigarette smoke condensate. AB - Measurement of tissue/cell DNA adducts represents a suitable monitor of carcinogen exposure because the majority of chemical mutagens/carcinogens react with DNA, forming covalent adducts, a key event in the initiation of chemical carcinogenesis. Investigations of DNA-adduct formation in vivo in white blood cells (WBC) versus target tissues, i.e. internal organs for most carcinogens, is expected to yield useful information about the suitability of WBC for biomonitoring and risk assessment. For this purpose, female ICR mice were given 0.4 mmole/kg benzo[a]pyrene (BP), 0.045 mmole/kg dibenzo[c,g]carbazole (DBC) or 2.47 mmole/kg safrole by oral gavage or 4 daily doses (equivalent to 3 cigarettes) of cigarette-smoke condensate (CSC) by topical application. At 24 h after dosing, DNA adducts were detected by a nuclease P1-enhanced 32P postlabeling assay [M.V. Reddy and K. Randerath, Carcinogenesis, 7 (1986) 1543] in WBC and internal tissues treated with individual carcinogens, while CSC treatment elicited aromatic adducts in most tissues but not in WBC. Adduct patterns of WBC DNA were qualitatively similar to those of internal organs, but adduct amounts varied. BP, a systemic carcinogen, bound nearly as much to WBC DNA as to target-tissue DNA samples; whereas the liver carcinogens, DBC and safrole, bound to WBC DNA considerably less (22- and 51-fold, respectively) compared with liver DNA. The number of adducts in 10(7) nucleotides of WBC, liver, lung, kidney and spleen DNA, respectively, were: 2, 5, 3, 2 and 3 with BP; 6, 131, 6, 14 and 4 with DBC; 5, 238, 3, 5 and 0.6 with safrole. For CSC, these values were 0, 1 and 0.02 in WBC, lung and spleen, respectively. Our results show that carcinogen binding to WBC DNA does not reflect binding to target-tissue DNA in a quantitative sense for the carcinogens studied except for BP, and that WBC are not suitable surrogates for monitoring CSC exposure by DNA-adduct measurement after topical application. The CSC data in mice was consistent with the previous findings in humans that smokers' tissues but not WBC show smoking-related bulky/aromatic DNA adducts, as measured by 32P-postlabeling. PMID- 2333085 TI - Chromosome damage in rat pulmonary alveolar macrophages following ozone inhalation. AB - To determine whether ozone is clastogenic at environmentally relevant exposure levels, rats were exposed for 6 h to 0.0, 0.12, 0.27, or 0.80 ppm ozone. The alveolar macrophages were isolated from animals sacrificed 28 h after the end of the exposure. The mitotic index and frequency of chromosome aberrations were determined. No change in the mitotic index was detected following 0.12 ppm ozone exposure. A significant decrease in mitotic index was observed after exposure to 0.27 ppm ozone; a significant (4-fold) increase in the frequency of dividing macrophages was detected following exposure to 0.8 ppm ozone. Only chromatid-type aberrations were observed. There was a significant increase in the frequency of cells with chromatid gaps and in the frequency of cells with chromatid deletions. Animals exposed to 0.27 ppm ozone had the highest proportion of cells with chromatid deletions (0.172) relative to background level (0.028). No exchanges or chromosome-type aberrations were detected in any of the animals. These data suggest that ozone, at relatively low levels, is clastogenic in macrophages from exposed rats. PMID- 2333086 TI - Use of rat primary lung cells for studying genotoxicity with the sister-chromatid exchange and micronucleus assays. AB - Primary culture of lung cells from CD rats was established for pulmonary genotoxicity studies using two genetic endpoints, sister-chromatid exchange (SCE) and micronucleus formation (MN). In the cell isolation study, a combined enzyme separation of rat lungs with trypsin (1.3 mg/ml) plus collagenase (50 U/ml) gave the highest yield of viable and colony-forming cells. For the MN assay, the cytokinesis block induced by cytochalasin B (CYB) was employed to enumerate MN in binucleated (BN) cells. Treatment of primary lung cells with 2 micrograms CYB/ml for two days appeared to be optimal for scoring micronuclei in CYB-induced BN cells. By this procedure, mitomycin C (MMC), triethylenemelamine, and benzo[a]pyrene caused a dose-related increase in micronucleated BN cells in vitro without metabolic activation. In the SCE assay, maximum second-division metaphases were obtained after cells were incubated with bromodeoxyuridine for 48 54 h. After this incubation time, high frequencies of SCE induced by MMC and 3 methylcholanthrene after in vitro exposure (without S9 activation) or in vivo exposure were observed. The results indicate that rat primary lung cells can metabolize polycyclic aromatic hydrocarbons and that this lung cell system is potentially useful for the detection of pulmonary genotoxicants. PMID- 2333087 TI - Indirect mechanism of lead-induced genotoxicity in cultured mammalian cells. AB - The data concerning the mutagenic, clastogenic and carcinogenic properties of inorganic lead compounds have been conflicting. To investigate whether the genotoxicity of lead is due to indirect effects such as interference with DNA repair processes, the induction of mutations, sister-chromatid exchanges and strand breaks by lead ions alone as well as in combination with UV light as a standard mutagen were determined. Lead acetate alone does not induce DNA-strand breaks in HeLa cells or mutations at the HPRT locus and sister-chromatid exchanges in V79 Chinese hamster cells. However, at all endpoints tested, lead ions interfere with the processing of UV-induced DNA damage. They inhibit the closing of DNA-strand breaks after UV irradiation and enhance the number of UV induced mutations and sister-chromatid exchanges, indicating an inhibition of DNA repair. These data point out the necessity to consider such indirect effects when assessing the genotoxicity of metal compounds. As possible mechanisms of repair inhibition we suggest either the interaction with repair enzymes such as polymerase or ligase or else the interaction with calcium-regulated processes, for example with calmodulin. PMID- 2333088 TI - Animals at work. PMID- 2333090 TI - Biological weapons: international treaty made domestic law. PMID- 2333089 TI - Lax enforcement of animal rules alleged. PMID- 2333091 TI - Chemical weapons: US to end modernization. PMID- 2333092 TI - BSE: spongiform encephalopathy found in cat. PMID- 2333093 TI - Scientific misconduct: Dingell tries again. PMID- 2333094 TI - Protein terminology tangle. PMID- 2333095 TI - Molecular genetic basis of the histo-blood group ABO system. AB - The histo-blood group ABO, the major human alloantigen system, involves three carbohydrate antigens (ABH). A, B and AB individuals express glycosyltransferase activities converting the H antigen into A or B antigens, whereas O(H) individuals lack such activity. Here we present a molecular basis for the ABO genotypes. The A and B genes differ in a few single-base substitutions, changing four amino-acid residues that may cause differences in A and B transferase specificity. A critical single-base deletion was found in the O gene, which results in an entirely different, inactive protein incapable of modifying the H antigen. PMID- 2333096 TI - Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. AB - Neurotransmitters are released at synapses by the Ca2(+)-regulated exocytosis of synaptic vesicles, which are specialized secretory organelles that store high concentrations of neurotransmitters. The rapid Ca2(+)-triggered fusion of synaptic vesicles is presumably mediated by specific proteins that must interact with Ca2+ and the phospholipid bilayer. We now report that the cytoplasmic domain of p65, a synaptic vesicle-specific protein that binds calmodulin contains an internally repeated sequence that is homologous to the regulatory C2-region of protein kinase C (PKC). The cytoplasmic domain of recombinant p65 binds acidic phospholipids with a specificity indicating an interaction of p65 with the hydrophobic core as well as the headgroups of the phospholipids. The binding specificity resembles PKC, except that p65 also binds calmodulin, placing the C2 regions in a context of potential Ca2(+)-regulation that is different from PKC. This is a novel homology between a cellular protein and the regulatory domain of protein kinase C. The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis. PMID- 2333097 TI - The gain of two chloroplast tRNA introns marks the green algal ancestors of land plants. AB - The relationship of green algae to land plants has greatly interested botanists for more than a century. In recent years, several characters, particularly ultrastructural ones, have been used to define a green algal group (Charophyceae) from which land plants are thought to have arisen. Here we provide the first molecular genetic evidence in support of the charophycean origin of land plants. Group II introns have previously been found in both the tRNAAla and tRNAIle genes of all land plant chloroplast DNAs examined, whereas all algae and eubacteria examined have uninterrupted genes. The distribution of these introns in Coleochaete, Nitella and Spirogyra, members of the Charophyceae, confirms that these taxa are part of the lineage that gave rise to land plants. Furthermore, the intron data place Coleochaete and Nitella closer to land plants than Spirogyra. These introns were most probably acquired by the chloroplast genome more than 400-500 million years ago, the time of land plant origin. PMID- 2333098 TI - Heparin specifically inhibits the inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned rat aortic smooth muscle cells in primary culture. AB - By measuring the 45Ca2+ movement in saponin-skinned primary cultured rat aortic smooth muscle cells, we examined the specificity of the inhibitory effect of heparin on the IP3-induced Ca2+ release. IP3 (100 mumol/l) markedly (98%) decreased the MgATP-dependent 45Ca2+ content in the non-mitochondrial Ca2+ stores in the presence of 1 mumol/l free Ca2+. Heparin (1-100 micrograms/ml) dose dependently inhibited this Ca2+ release by IP3. In Ca2(+)-free solution, heparin (100 micrograms/ml) inhibited the increases in 45Ca2+ efflux rate evoked by 10 mumol/l IP3. De-N-sulfated heparin did not inhibit the IP3-induced Ca2+ release. Hyaluronic acid, heparan sulfate, chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C and 2,6-disulfated D-glucosamine had no inhibitory effects on the IP3-induced Ca2+ release. High concentrations (over 1 mg/ml) of heparin inhibited the 45Ca2+ influx and decreased the 45Ca2+ content in skinned cells. These results suggest that heparin (1-100 micrograms/ml) specifically inhibits the IP3-induced increase in Ca2+ permeability of Ca2+ stores and that three sulfate groups at different locations on the molecule of heparin, two at the D glucosamine and one at the iduronic acid, may be important for this action, in skinned vascular smooth muscle cells, in culture. PMID- 2333099 TI - Different muscarinic receptors mediate autoinhibition of acetylcholine release and vagally-induced vasoconstriction in the rat isolated perfused heart. AB - Experiments were carried out on rat isolated perfused hearts with both vagus nerves attached. The acetylcholine stores were labelled with [14C]-choline. The effects of muscarinic receptor antagonists on the [14C]-overflow and increase in perfusion pressure evoked by vagus nerve stimulation (10 Hz, 4-10 mA) were studied in order to determine the muscarinic receptor type involved in autoinhibition of acetylcholine release and vagally-induced vasoconstriction in the rat heart. Stimulation of the vagus nerves (1200 pulses) caused an increase in [14C]-overflow and in perfusion pressure which was significantly reduced by hexamethonium 500 mumol/l and abolished by tetrodotoxin 0.3 mumol/l or perfusion with Ca2(+)-free solution. The fractional rate of evoked [14C]-overflow per pulse upon stimulation at 10 Hz (720 pulses) was doubled in the presence of the non selective antagonist atropine (0.01-1 mumol/l) as well as in that of the M2 selective compounds methoctramine (0.1 mumol/l) and AF-DX 116 (0.1-1 mumol/l), but remained unaffected by the M3-selective hexahydrosiladifenidol (0.1 mumol/l). The increase in perfusion pressure upon nerve stimulation was reduced by atropine (0.01 mumol/l) or hexahydrosiladifenidol (0.1 mumol/l) to approximately 50% and increased by about 50% in the presence of AF-DX 116 (0.1 mumol/l). The results show that the autoinhibition of acetylcholine release in the rat heart is mediated by M2 receptors. On the other hand, the increase in perfusion pressure upon vagus nerve stimulation is caused by a different muscarinic receptor, more sensitive to hexahydrosiladifenidol than to M2-selective antagonists. PMID- 2333100 TI - Differential effects of calcium channel antagonists (omega-conotoxin GVIA, nifedipine, verapamil) on the electrically-evoked release of [3H]acetylcholine from the myenteric plexus, phrenic nerve and neocortex of rats. AB - Electrically-evoked release of [3H]acetylcholine from autonomic neurons (myenteric plexus), motoneurons (phrenic nerve) and the central nervous system (neocortex) was investigated in the presence and absence of the calcium channel antagonists omega-conotoxin GVIA, nifedipine and verapamil, whereby the same species (rat) was used in all experiments. Release of [3H]acetylcholine was measured after incubation of the tissue with [3H]choline. omega-Conotoxin GVIA markedly reduced (70%) the evoked release of [3H]acetylcholine from the myenteric plexus of the small intestine (IC50: 0.7 nmol/l) with a similar potency at 3 and 10 Hz stimulation. An increase in the extracellular calcium concentration attenuated the inhibitory effect of omega-conotoxin GVIA. Release of [3H]acetylcholine from the rat neocortex was also inhibited (90%) by omega conotoxin GVIA, but the potency was 19-fold lower (IC50: 13 nmol/l). However, the release of [3H]acetylcholine from the phrenic nerve was not reduced by omega conotoxin GVIA (100 nmol/l) at 1.8 mmol/l calcium (normal concentration), whereas omega-conotoxin GVIA inhibited evoked [3H]acetylcholine release by 47% at 0.9 mmol/l calcium. Neither nifedipine (0.1 and 1 mumol/l) nor verapamil (0.1, 1 and 10 mumol/l) modified the evoked release of [3H]acetylcholine from the myenteric plexus and the phrenic nerve. Acetylcholine release from different neurons appears to be regulated by different types of calcium channels. N-type channels play the dominant role in regulating acetylcholine release from both the myenteric plexus and the neocortex, whereas acetylcholine release from motor nerves is regulated by calcium channel(s) not yet characterized. PMID- 2333101 TI - Age-related changes in neuronal uptake of noradrenaline. AB - Age-related changes in the neuronal uptake of noradrenaline were studied in the vas deferens of 4-, 12- and 20-months old rats by determining the potentiating effect of cocaine on concentration-effect curves to noradrenaline and by evaluating the kinetic parameters (Vmax and apparent Km) of neuronal 3H noradrenaline uptake. Since the neurotransmitters released by nerve terminals and the density of noradrenergic innervation are different in the epididymal and prostatic portion of the vas, the experiments were carried out in these two portions of the organ. In the epididymal portion, the ratio between EC50 for noradrenaline in the presence and in the absence of cocaine was reduced in tissues of middle-aged (12-months) and old (20-months) animals when compared with young (4-months) animals. The pD2 values for noradrenaline in the absence of cocaine and the kinetic parameters for neuronal 3H-noradrenaline uptake were not modified by ageing. Thus, in the epididymal portion there was no age-related change in neuronal uptake. The age-related decrease in the cocaine-induced supersensitivity to noradrenaline was due to an age-related decrease in the pD2 value for noradrenaline observed in the presence of cocaine, suggesting postsynaptic changes. In the prostatic portion, the ratio between EC50 for noradrenaline in the presence and in the absence of cocaine was also reduced in tissues of old animals (20-months) when compared with middle-aged and young animals. The pD2 value for noradrenaline in the absence of cocaine obtained in the prostatic portion of 20-months old rats was higher than that in the younger groups (4- and 12-months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333102 TI - Renal failure in haemorrhagic shock in dogs: salutary effects of the calcium entry blocker felodipine. AB - The efficacy of felodipine, a dihydropyridine calcium entry blocker to restore renal function was investigated in Wiggers model of haemorrhagic shock. Mongrel dogs were anaesthetized with sodium pentobarbital and subjected to haemorrhagic shock by allowing the animals to bleed into a reservoir. After maintaining the hypotensive state (mean blood pressure 40-45 mm Hg) for a period of 150 min, the blood was reinfused and the recovery of the various parameters were monitored for an additional 120 min. These studies were conducted in three different groups of dogs: (A) Solvent control, (B) Felodipine 0.01 mumol/kg i.v., administered 10 min prior to reinfusion of the blood, and (C) Felodipine 0.01 mumol/kg i.v., administered prior to haemorrhage. In all the three groups arterial blood pressure returned to similar basal levels following reinfusion. Felodipine administration prior to haemorrhage or before reinfusion (Group B and C) resulted in a 80-95% recovery in the renal blood flow, 60-65% in the glomerular filtration rate, 150-300% in the urine volume and 80-100% in the urinary sodium and potassium excretions. In the vehicle-treated control group, despite a 45% recovery in the renal blood flow, renal function was not restored following reinfusion. The observations made in these studies suggest that felodipine, an arteriolar dilator which also possesses natriuretic properties, could be clinically useful in the treatment of renal failure in haemorrhagic shock. Prevention of cellular calcium overload during ischaemia and reperfusion by this dihydropyridine derivative, may account for its ability to preserve vascular as well as tubular function. PMID- 2333103 TI - Comparison of relaxation responses of vascular and non-vascular smooth muscle to endothelium-derived relaxing factor (EDRF), acidified sodium nitrite (NO) and sodium nitroprusside. AB - Smooth muscle relaxant activity of endothelium-derived relaxing factor (EDRF) released from columns of cultured bovine endothelial cells by bradykinin (0.1-3 nmol/l) was measured in four non-vascular preparations: guinea-pig taenia caeci, guinea-pig trachea, rat stomach (fundus) and rat anococcygeus. Each preparation was contracted to a steady level of force with a variety of agonists such that they relaxed optimally to sodium nitroprusside (SNP). The EDRF-induced relaxations in each preparation were compared with those obtained in de endothelialized ring preparations of greyhound coronary artery by means of paired bioassays run in parallel. EDRF released from the endothelial cell columns caused 80-100% relaxation of the coronary artery, 40-80% in the guinea-pig taenia caeci, 50-70% in the rat anococcygeus, 5-8% in the guinea-pig trachea and was undetectable in the rat stomach strip. By comparison, SNP caused maximal relaxation in all tissues compared with the coronary artery. In separate organ bath experiments the sensitivity to nitric oxide (NO: generated by adding acidified solutions of NaNO2) and SNP was compared in each preparation. SNP caused maximal relaxation in all tissues with the following order of potency: dog coronary artery greater than guinea-pig trachea greater than guinea-pig taenia = rat anococcygeus greater than rat stomach strip. In contrast, the concentration of acidified NaNO2 (NO, 300 nmol/l) that caused 96 +/- 4% relaxation in the dog coronary artery caused 84 +/- 7% and 48 +/- 1% relaxation in the taenia and anococcygeus respectively. No response attributable to NO was detected in either the trachea or rat stomach strip.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333104 TI - Relaxation by adenosine and its analogs of potassium-contracted human coronary arteries. AB - The present study was an attempt to characterize the adenosine receptor in human coronary arteries, and to establish the dependence of the relaxations mediated by this receptor on a functional endothelium. Human coronary arteries were obtained from organ donors. Adenosine and its analogs (5'-N-ethyl-carboxamido-adenosine, NECA; N6-L-phenylisopropyladenosine, L-PIA; 2-chloroadenosine, CAD), all inhibited the contraction induced by 25 mmol/l KCl in a concentration-dependent manner and the order of potency was found to be: NECA greater than CAD greater than L-PIA greater than adenosine. These relaxations were antagonized by 8 phenyltheophylline (8PT). At higher concentrations of KCl, the relaxations were attenuated. In rings which relaxed in response to endothelium-dependent relaxing agents (bradykinin and A23187), NECA and CAD produced relaxations similar to those produced in rings which did not show endothelium-dependent responses. The results suggest that the coronary adenosine receptor (probably A2) mediates relaxations which may not be dependent on the relaxing function of the endothelium. PMID- 2333105 TI - Lessons from neurologic practice. An unusual cause of progressive spastic paraparesis. PMID- 2333106 TI - AIDS: testing and reporting. PMID- 2333107 TI - Informed consent for AIDS testing. Or: whose vein is it anyway? PMID- 2333108 TI - HIV testing in North Carolina. PMID- 2333109 TI - Lithium treatment and bipolar disorders in childhood. PMID- 2333110 TI - Schemes gang aft agley. Thallium poisoning. PMID- 2333111 TI - Pardon me? PMID- 2333112 TI - Access--or lack of access--to care. PMID- 2333113 TI - AIDS legislation and public health. PMID- 2333114 TI - Blue Cross and Blue Shield and cesarean section. PMID- 2333115 TI - A question about Prozac and arthralgias. PMID- 2333116 TI - Quality problem reporting with prescription and over-the-counter drugs. PMID- 2333117 TI - Attending to quality assurance, economics, and the nursing shortage. PMID- 2333118 TI - The Harvard RVS and it's potential impact on nephrologists. PMID- 2333119 TI - Why the need to study mortality among dialysis patients. PMID- 2333120 TI - Carrier payment delays biggest problem for ESRD facilities. PMID- 2333121 TI - ANNA: challenges in nursing care. A Q&A with outgoing President Evelyn Butera. American Nephrology Nurses Association. PMID- 2333122 TI - Taking a look at the organ procurement picture. PMID- 2333123 TI - Descriptive epidemiology of primary tumors of the spinal cord and spinal meninges in Los Angeles County, 1972-1985. AB - This report presents data on the distribution of 462 primary tumors of the spinal cord and spinal meninges (both benign and malignant) diagnosed among residents of Los Angeles County from 1972 to 1985. Incidence rates of gliomas, meningiomas, nerve sheath tumors, and all histologic types combined are presented for specific age, sex, and ethnic groups. The highest rates are seen for meningiomas in women (age-adjusted rate 3/million/year compared to 1/million/year for the other two histologic types in women and for each of the three types in men). Proportional incidence ratios for spinal tumors are elevated among men and women born in Eastern Europe and among Jewish residents of Los Angeles County. The incidence rates appear not to relate to the social class. PMID- 2333124 TI - Risk factors for stroke in rural areas of the People's Republic of China: results of a case-control study. AB - A case-control study on stroke was carried out in 1985 in conjunction with a prevalence survey on neurologic disorders in 22 rural communities of the People's Republic of China. 585 cases of stroke, detected from the survey, together with an equal number of matched controls were investigated. The statistically significant factors associated with stroke in this study were: hypertension (history, findings at examination); high salt intake; family member(s) with cerebrovascular disease and/or hypertension; heart disease (history, abnormal findings at examination); history of transient ischemic attacks, and arteriosclerotic funduscopic findings. These factors were analyzed separately for hemorrhagic and ischemic strokes. PMID- 2333125 TI - Demographic characteristics of multiple sclerosis in south east Wales. AB - The non-uniform distribution of multiple sclerosis in the United Kingdom has been attributed to genetic, exogenous and selective factors. Within the county of South Glamorgan the disease is most prevalent amongst middle-aged married or divorced caucasian women, born in England rather than Wales, occupying flats located in affluent communities with superior amenities where rates of owner occupation are high. The disease is least prevalent amongst young single Welsh born or non-caucasian males living in rented accommodation located in less affluent communities with a higher population density. These observations may, in part, be related to superior ascertainment of the former group, but some, as yet unidentified, characteristic of the environment may also be relevant. PMID- 2333126 TI - Prognosis and risk factors in febrile convulsions: a prospective study of 150 children in Kuwait. AB - One hundred and fifty children with febrile convulsions (FC) were followed up for 3-10 years. They were divided into two groups: group A consisted of 120 children whose disorder was under control, and group B 30 patients in whom the disorder was not under control. Risk factors for uncontrolled FC and later development of epilepsy were looked into. In group A, 8 patients (6.6%) developed epilepsy, while another 3 (2.5%) had a single afebrile seizure. In group B, 10 (33.3%) children developed epilepsy, while 1 (3.3%) had a single afebrile seizure. The difference in the later occurrence of epilepsy between the two groups was statistically significant. PMID- 2333127 TI - Assessment of growth in sudden infant death syndrome. AB - Autopsy reports from 208 cases of sudden infant death syndrome (SIDS) were reviewed and divided into three groups: group 1, term infants without infection; group 2, term infants with mild infection, and group 3, premature infants. The brain weights of these children were matched by age and body length, separately for males and females, with reference values and a group of 53 children born at term who died from conditions that did not affect the central nervous system. The brains of children in groups 1 and 2 were heavier than reference values when matched by age and body length. The differences between group 1 and reference values tended to increase with age; however, when matched by body length, this tendency was no longer observed. Body lengths of SIDS cases at death were also greater than reference values. There was no difference between brain weights of children in groups 1 and 2. These data suggest that the enlarged brains were present from birth rather than the result of disproportionate postnatal growth. The cause of increased brain size in SIDS cases is unknown, as is its possible role in the events leading to sudden death. PMID- 2333128 TI - Intracranial meningiomas. Comparison of plain and contrast-enhanced examinations in CT and MRI. AB - Fifty patients with intracranial meningiomas underwent plain and contrast enhanced examinations with CT and MRI. Each of the MR studies consisted of three plain (T1, proton density and T2-weighted) and a post-contrast series (0.1 mmol Gd-DTPA/kg body weight). All techniques (plain CT, plain MRI, contrast-enhanced CT, contrast-enhanced MRI) proved to be highly efficient as regards tumour detection: depending on the technique, an intracranial lesion was demonstrated in 47-50 cases. The image contrast was assessed as good or excellent in 21 cases having plain CT and in 33 cases having plain MRI, but in 46 and 50 of the contrast-enhanced CT and MRI studies respectively. Adequate tumour delineation was achieved in 18 cases with plain CT, in 35 cases with plain MRI and in 46 and 50 cases of the contrast-enhanced CT and MRI examinations. The contrast-enhanced studies proved to be superior to the plain CT and MRI studies as regards image contrast and tumor delineation. Because of the methodological advantages of the MRI technique, contrast-enhanced MRI was judged to be slightly superior to contrast-enhanced CT. PMID- 2333129 TI - Gd-DTPA enhanced MR imaging in intracranial tuberculosis. AB - Twenty-six patients with intracranial tuberculosis (Tb) (10 with acute meningitis, 5 with chronic meningitis, 5 with meningitic sequelae and 6 with localized tuberculoma(s)) were examined with MR before and after Gd-DTPA enhancement (0.1 mmol/kg), using 2.0T superconducting unit, and the images were retrospectively analyzed and compared with CT scans. Without Gd-DTPA enhancement, the MR images were generally insensitive to detection of active meningeal inflammation and granulomas. The signal intensity of granulomas was usually isointense to gray matter on both T1- and T2-weighted images, whether they were associated with diffuse meningitis or presented as localized tuberculoma(s). A few granulomas showed focal hypointensity on T2-weighted images. Calcifications seen on CT of the meningitic sequelae group usually appeared markedly hypointense on all spin-echo sequences. On Gd-DTPA enhanced T1-weighted images, abnormal meningeal enhancement indicating active inflammation was conspicuous, and the granulomas often appeared as conglomerated ring-enhancing nodules, which seems to be characteristic of granulomas. Thin rim enhancement around the suprasellar calcifications were observed in two out of 5 patients with meningitic sequelae. Compared with CT, MR detected a few more ischemic infarcts, hemorrhagic infarcts, meningeal enhancement and granulomas in the acute meningitis group, but missed small calcifications in the basal cisterns well shown on CT in the sequelae group. Otherwise, MR generally matched CT scans. MR imaging appears to be superior to CT in evaluation of active intracranial Tb only if Gd-DTPA is used, while CT is better than MR in evaluating meningitic sequelae with calcification. PMID- 2333130 TI - Neuroradiologic findings in leptomeningeal carcinomatosis: the value interest of gadolinium-enhanced MRI. AB - Four patients with leptomeningeal metastases documented by neuroradiological examinations are reported. All had central nervous system or systemic neoplasms and showed clinical signs of carcinomatous meningitis. Gadolinium-enhanced MRI (Gd-MRI) disclosed for each patient pathological foci, allowing delineation of the extent of meningeal disease. Although non-specific, these findings, combined with the clinical context and CSF analysis, may lead to a rapid diagnosis and treatment of carcinomatous meningitis, even when malignant cells are not detected in the cerebrospinal fluid. PMID- 2333131 TI - Cortical and subcortical hyperperfusion during migraine and cluster headache measured by Xe CT-CBF. AB - High-resolution, color-coded images of local cerebral blood flow (LCBF) were made utilizing stable xenon-enhanced computed tomography among patients with common migraine (n = 18), classic migraine (n = 12) and cluster headache (n = 5). During spontaneously occurring headache in common and classic migraine patients, LCBF values for cerebral cortex and subcortical gray and white matter were diffusely increased by 20-40% with the exception of the occipital lobes. LCBF increases involved both hemispheres whether the head pain was unilateral or bilateral. No significant differences were noted in the degree or pattern of LCBF increases during headaches of common and classic migraineurs. Similar cerebral hyperperfusion of greater magnitude was observed during cluster headaches but was more prominent on the side of the head pain. Present observations do not support the hypothesis of spreading cortical depression as a cause of classic migraine. From a hemodynamic viewpoint, LCBF increases during headaches of common or classic migraine or cluster appear similar. Evidence is adduced that sympathetic hypofunction with denervation hypersensitivity of cerebral vessels plays a role in the cerebral hyperperfusion of migraine headaches. More pronounced unilateral autonomic derangements appear to account for the symptoms and cerebral hyperperfusion associated with cluster headaches. PMID- 2333132 TI - Early detection of cerebral infarction by 31P spectroscopic imaging. AB - Recent advances in magnetic resonance spectroscopy permit noninvasive study of brain metabolism in vivo, 31P spectroscopic imaging being the method for evaluation of localized phosphorous metabolism. Experimentally, an ischemic hypoxic brain insult is characterized by depletion of high energy metabolites. These changes are seen immediately after an ischemic insult. We had the opportunity of carrying out 31P spectroscopic imaging of hyperacute cerebral infarction, while MRI and CT were negative. Cerebral infarction of the middle cerebral artery territory was suggested by 31P spectroscopic imaging, which was closely consistent with a later-developing region of low density on CT. In cerebral infarction, early detection of the lesion is a useful pointer to the patient's prognosis, making 31P spectroscopic imaging a potential tool. PMID- 2333133 TI - Magnetic resonance evaluation of severe neurological disorders in eclampsia. AB - A patient with eclampsia and severe but reversible neurological disorders is presented. Initial magnetic resonance imaging (MRI) revealed multiple hyperintense areas throughout the brain and brainstem that were consistent with ischemia and/or edema. Despite these diffuse lesions extending to the brainstem, the patient made a progressive neurological recovery and a follow-up MRI on day 21 demonstrated complete resolution of the hyperintense foci. MRI abnormalities were found to correlate more closely with clinical and electrophysiological data than CT findings. PMID- 2333134 TI - Corpus callosum lipoma with frontal encephalocele. AB - Computed tomographic and plain X-ray observations in a patient with corpus callosum lipoma associated with frontal encephalocele are reported. The rarity of the lesion and the specific diagnostic criteria on CT are emphasised. PMID- 2333135 TI - Parapharyngeal meningioma extending from the intracranial space. AB - A 50-year old woman with a giant parapharyngeal meningioma extending from the intracranial cavity was admitted to our hospital. The parapharyngeal tumor was biopsied using the transoral approach and a histological section diagnosis suggested meningioma. Thereafter, further examination by magnetic resonance images (MRI) and contrast enhanced CT scans revealed a diffuse meningioma en plaque in the posterior fossa. Invasion extended from the clival dura to the right sigmoid sinus. The extracranial extension of a meningioma is very rare but a few cases have been reported. In almost all of the reported cases, a large intracranial meningioma was simultaneously or previously verified by CT scans. Our case was special in that the intracranial mass was not voluminous but showed en plaque extension, and also because the pathway of the extracranial extension through the jugular foramen was clearly visualized by CT and MRI. Obliteration and invasion of the right sigmoid sinus and the internal jugular vein by tumor were also demonstrated. PMID- 2333136 TI - Gadolinium-DTPA-enhanced MR imaging in the diagnosis of spinal epidural haematoma. Report of a case. AB - A case of spinal epidural haematoma diagnosed by means of Gadolinium-DTPA enhanced MR imaging is described. The sensitivity of this recent technique is underlined. PMID- 2333137 TI - Epidural gas: an unusual complication of metastatic oesophageal carcinoma. AB - Epidural gas occurring in benign disease is well documented. Gas formation within an epidural metastasis, which has not been previously reported, was demonstrated using computed myelography. PMID- 2333138 TI - Fatal complications after myelography with meglumine diatrizoate. AB - A case of inadvertent intrathecal injection of diatrizoate meglumine is presented. After myelography with 10 ml i.e. 6.5 g Angiografin, a 76-year-old man rapidly developed myoclonus, drowsiness and excessive metabolic acidosis. He died only a few hours later. Postmortem showed non-specific brain edema. RP-HPL Chromatography confirmed high concentration of the contrast medium in CSF (6 mg/ml) which must have induced refractory central nervous dysregulation. The lethal effects of the misapplication of this agent on the nervous system are discussed. PMID- 2333139 TI - Mitochondrial encephalomyopathy (MELAS) with mental disorder. CT, MRI and SPECT findings. AB - A case of mitochondrial encephalomyopathy (MELAS) with mental disorder is reported. The SPECT study using 123I-iodoamphetamine (IMP) and MRI study revealed abnormality in the left parieto-occipital areas without abnormality in the brain CT or brain scintigram. These findings suggest a localized dysfunction of the brain capillary endothelium in association with the cerebral involvement of mitochondrial encephalomyopathy. PMID- 2333140 TI - Fluctuating MR images with mitochondrial encephalopathy, lactic acidosis, stroke like syndrome (MELAS). PMID- 2333141 TI - Intraosseous location of posterior fossa posttraumatic leptomeningeal cyst. Demonstration by computerized tomography. PMID- 2333142 TI - MR imaging of persistent primitive trigeminal artery. PMID- 2333143 TI - Antidromic firing occurs spontaneously on thalamic relay neurons: triggering of ectopic action potentials by somatic intrinsic burst discharges. AB - Possible dynamic relationships between orthodromically conducted somatic bursts and antidromic impulses arising from presynaptic endings of thalamocortical neurons were explored. Evoked or spontaneous bursts were recorded from 125 identified thalamic relay neurons in 36 anesthetized rats using extracellular microelectrodes. Evoked bursts were obtained by electrical stimulation of either the neocortex or the peripheral activation field. Spontaneous antidromic firing appeared only during periods of (or an expected) rapid somatic intrinsic burst discharge. Ectopic axonal impulses occurred either separately, or clustered in doublets or triplets having relatively long-lasting intervals; these slow bursts represented a proportion of about 12% of evoked and 20% of spontaneous whole bursts. Separate ectopic action potentials could also appear several milliseconds after rapid bursts, producing peculiar long last-interval bursts; about 15% of the whole bursts were of this long interval type. The probability that an ectopic axonal impulse will occur after a rapid burst increases with the number of its action potentials, suggesting that the duration of orthodromic burst firing might contribute to the triggering of ectopic impulses. For 52% of the neurons tested, the activation threshold of their axon terminals decreased just before or immediately after rapid somatic bursts. Since no excitability changes were observed in thalamocortical axons of the white matter, the ectopic action potential generators were probably located on presynaptic endings. During a transient deafferentation of thalamic neurons induced by intrathalamic microinjection of a magnesium solution, neither burst activity nor spontaneous antidromic firing were observed, suggesting that thalamic orthodromic burst discharges are required for presynaptic impulse generation. In conclusion, somatic intrinsic bursts traveling orthodromically along thalamocortical axons might be involved in triggering presynaptic impulses on parent and possibly on nearby thalamic cells. Since a spontaneous antidromic action potential is able to trigger a rapid burst [Pinault (1988) Eur. J. Neurosci. Suppl. P. 246; Pinault and Pumain (1989) Neuroscience 31, 625-637], it is postulated that excitatory interactions between presynaptic endings might be involved in intrinsic burst synchronization processes. PMID- 2333144 TI - Hippocampal mossy fibers and radial-maze learning in the mouse: a correlation with spatial working memory but not with non-spatial reference memory. AB - One hundred and eight male mice from nine different inbred strains were tested for two aspects of learning in an eight-arm radial maze. In the first experimental arrangement of the maze, measuring spatial working memory, clear strain differences were found on the fifth day of training. Furthermore, this type of learning showed a high positive correlation with the size of the intra- and infrapyramidal hippocampal mossy fiber terminal field as revealed with Timm's staining. In the second experiment, in which non-spatial reference memory was tested, significant strain differences were found for the learning variables, but there were no significant covariations with the sizes of the intra- and infrapyramidal mossy fiber terminal fields. These results, combined with previous data, suggest that heritable variations of the hippocampal intra- and infrapyramidal mossy fiber projection influence processes determining spatial learning capabilities in mice. PMID- 2333145 TI - Effects of histamine on dentate granule cells in vitro. AB - Hippocampal slices from rat brain were exposed to histamine and related substances in a perfusion chamber. Granule cells of the dentate gyrus were studied with conventional extra- and intracellular recording and a single electrode voltage clamp. Histamine caused, through activation of H(2)-receptors, a small depolarization, an increase in the number of synaptic and action potentials, a block of the long lasting (but not the early) component of spike afterhyperpolarizations and a reduction of the accommodation of action potential firing. These effects were mimicked by forskolin (suggests activation of adenylate cyclase). In voltage clamp, histamine blocked a long lasting calcium dependent outward tail current without any reduction of inward current. Thus histamine selectively blocks the late calcium-dependent potassium current in dentate granule cells which receive histaminergic input from the posterior hypothalamus. Histamine also reduces the field excitatory postsynaptic potential evoked by perforant path stimulation. These actions allow for a powerful modulation of excitatory signals and an effective regulation of hippocampal excitability. PMID- 2333146 TI - Excitotoxin-induced degeneration of rat vagal afferent neurons. AB - The inferior vagal or nodose ganglion contains the perikarya of vagal afferent neurons that function as cardiopulmonary and abdominal visceral receptors as well as aortic arch baroreceptors. In this study we have sought to utilize the axon sparing properties of the excitotoxins kainic acid, N-methyl-D-aspartic acid and alpha-amino-3-hydroxy-4-isoxazolepropionic acid to destroy the perikarya of these sensory neurons and thus selectively de-afferent the vagus in the rat. Kainic acid (0.5 nmol/microliters, 2 X 2 microliters) was applied topically to both nodose ganglia and the rats were allowed to recover for 7-8 days. Baroreceptor heart rate reflex activity was assessed in these conscious rats. Baroreceptor heart rate reflex gain was reduced (-51%) in kainic acid-treated rats, as was the maximal reflex bradycardia induced by the pressor agent, phenylephrine. Kainic acid treatment did not alter resting mean arterial pressure or heart rate. Vagal efferent neurons were spared by kainic acid treatment since bradycardic responses to electrical stimulation of the peripheral end of a cut vagus were not impaired. Histological studies showed marked destruction of perikarya within the nodose ganglia of kainic acid-treated rats: inflammatory and degenerative changes were evident at 2 days, and at 10 days there was considerable loss of neuronal cell bodies, but sparing of axons. Topical application to the nodose ganglion of alpha methyl-DL-aspartic acid (6.8 nmol/microliters, 2 X 2 microliters), a non excitotoxic dicarboxylic acid, failed to alter baroreflex sensitivity or produce perikaryal degeneration in nodose ganglia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333147 TI - Long-term chemical sympathectomy leads to an increase of neuropeptide Y immunoreactivity in cerebrovascular nerves and iris of the developing rat. AB - Short-term (surgical) and long-term (chemical) sympathectomy have revealed the presence of a population of neuropeptide Y-like immunoreactive nerve fibres which do not degenerate in parallel with noradrenaline-containing nerves supplying cerebral vessels and the iris of the rat. Two days after bilateral removal of the superior and middle cervical ganglia of 7-week-old rats, noradrenaline-containing nerves could not be detected along any of the arteries of the rat circle of Willis or of the iris, but 18-32% of neuropeptide Y-like immunoreactive nerves remained. Long-term treatment (6 weeks) with guanethidine commencing in developing 1-week-old rats caused degeneration of the sympathetic neurons in cervical ganglia and disappearance of 5-hydroxydopamine-labelled nerves (that showed dense-cored vesicles at the electron microscope level) from rat cerebral vessels, but did not significantly change the density of neuropeptide Y-like immunoreactive axons on the vessels. Furthermore, whilst in control rats neuropeptide Y-like immunoreactivity was localized largely within 5 hydroxydopamine-labelled cerebrovascular nerves, after long-term sympathectomy with guanethidine, neuropeptide Y-like immunoreactivity was seen only in nerves lacking small dense-cored vesicles. A small number of catecholamine-containing nerves appeared along the internal carotid and anterior cerebral arteries after long-term sympathectomy; these may arise from neurons of central origin. These results suggest that as a consequence of long-term sympathectomy with guanethidine, compensatory changes occur, involving an increase in the expression of neuropeptide Y-like immunoreactivity in non-sympathetic axons in cerebrovascular nerves and iris of the rat. In contrast, the neuropeptide Y-like immunoreactive nerves in the dura mater appear to be entirely sympathetic, since none were present after short-term sympathectomy and none appeared after long term sympathectomy. PMID- 2333148 TI - Effects of motor cortex and single muscle stimulation on neurons of the lateral vestibular nucleus in the rat. AB - The neuronal responses to stimulation of motor cortical sites and of forelimb single muscles were studied in the lateral vestibular nucleus of anaesthetized rats. Of the 228 neurons tested for response to stimulation of contralateral motor cortex, 63% responded to cortical sites controlling extensor muscles and 30% to those controlling flexors. The corresponding figures for responders to ipsilateral stimulation were 34 and 21%. Vestibulospinal units responded to cortical sites controlling extensor and flexor muscles whereas the remaining lateral vestibular nucleus neurons, very reactive to cortical sites controlling extensor muscles, responded little to contralateral and not at all to ipsilateral cortical sites controlling flexor muscles. The effects evoked by contralateral cortical sites controlling extensors varied, those induced by cortical sites controlling flexors were inhibitory in 77% of cases. The responses to ipsilateral motor cortex stimulation differed not so much by cortical sites controlling extensor or flexor muscles as by whether the neuron was in the dorsal or ventral zone of the lateral vestibular nucleus: mixed in the former, all inhibitory in the latter. Of the lateral vestibular nucleus units tested for response to stimulation of ipsilateral or contralateral forelimb distal muscles, only 11% responded. All the vestibulospinal units responsive to muscle stimulation lay in the dorsal zone of the nucleus. The remainder, dorsal or ventral, were not responsive to contralateral muscles. Single lateral vestibular nucleus cells influenced both by ipsilateral muscle and by contralateral motor cortex made up 24% of the pool, vestibulospinal and non-vestibulospinal. They fell into three groups: responsive to one or both structures but responding more strongly to combined stimulation; responsive to each of the two structures but showing a response to combined stimulation not significantly different from that evoked by the cortex alone; responsive only to combined stimulation. The lateral vestibular nucleus units included in these three groups accounted for 29% of those tested for response to extensor muscles and cortical sites controlling extensors and 15% of those tested for response to flexor muscles and cortical sites controlling flexors. Twenty-five per cent of the vestibulospinal neurons responded both to contralateral muscles and to ipsilateral motor cortex stimulation but none of the non-vestibulospinal neurons responded to both. All the responders to both were in the dorsal zone of the lateral vestibular nucleus and responded to extensor stimuli, always in the same way. These results indicate that motor cortex output exerts a major influence on lateral vestibular nucleus discharges, while the muscle afferents have a modulatory influence on the lateral vestibular nucleus responses to cortex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2333149 TI - Large diameter primary afferent input is required for expression of the Cat-301 proteoglycan on the surface of motor neurons. AB - The expression of a cell surface proteoglycan, recognized by monoclonal antibody Cat-301, is regulated by neuronal activity in early life. Here we report that the expression of the Cat-301 proteoglycan on motor neurons depends on primary afferent input in the early postnatal period. Previously we showed that in two different systems, Y-cells in the cat lateral geniculate nucleus and motor neurons in the hamster spinal cord, the expression of the Cat-301 antigen requires neuronal activity during a circumscribed period in development. Disrupting the activity of Y-cells (by dark rearing or by monocular lid suture) or of motor neurons (by sciatic nerve crush or by spinal cord lesion) during the early postnatal period prevents Cat-301 expression. Disrupting neuronal activity in adults has no effect on Cat-301 expression. The onset of Cat-301 expression corresponds to the end of the period of activity-dependent development. In order to further dissect the components of the segmental reflex are required for the expression of Cat-301 on motor neurons, here we evaluated the effect of deafferentation by dorsal rhizotomy. In adult animals two weeks after deafferentation all sciatic motor neurons continue to express Cat-301. In contrast, in neonates two weeks after deafferentation the normal developmental expression of Cat-301 is reduced and less than 50% of sciatic motor neurons express Cat-301. We next selectively lesioned the small diameter afferents using the neurotoxin capsaicin. In contrast to rhizotomy, neonatal deletion of small diameter afferents has no effect on the development of Cat-301 expression on motor neurons. These results imply that input relayed by large diameter primary afferents (probably those conveying muscle and/or joint information) is required for normal maturation of motor neuronal properties during early life. They also provide further evidence for activity-dependent maturation of motor neurons. PMID- 2333150 TI - Two new monoclonal antibodies provide immunohistochemical evidence for the unique biochemical similarity of the mouse globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata. AB - Similarities in cellular morphology, afferentation, efferentation, and neurotransmitter content between the internal and external parts of the pallidum and the substantia nigra pars reticulata have long been noted. Here we present evidence that the globus pallidus, entopedunucular nucleus and substantia nigra pars reticulata are more closely related to each other antigenically than to any other anatomical subdivision in the murine central nervous system. In a monoclonal antibody library composed of 20 distinctive lines selected from 300 hybridomas screened immunohistochemically on mouse brain sagittal sections we found two antibodies whose staining patterns distinguish the pallidum and substantia nigra pars reticulata from all other brain gray matter regions but stain these two divisions similarly. One monoclonal antibody, F1-134, stains all brain gray matter regions moderately but gives intense staining of the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata only. Another monoclonal antibody, F1-20, stains different brain gray matter regions to varying degrees but shows a complete and exclusive exclusion of staining from the globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata. These results support the tripartite pallidum hypothesis. This study also provides an example of how the monoclonal antibody library strategy can be applied to general problems of brain organization. PMID- 2333151 TI - Electrically evoked noradrenaline release in the rat hypothalamic paraventricular nucleus studied by in vivo electrochemistry: characterization and facilitation by increasing the stimulation frequency. AB - The hypothalamic paraventricular nucleus is densely innervated by noradrenergic terminals mainly originating in the A1 group within the ventrolateral medulla. An oxidation signal corresponding to extracellular catechols was recorded from the paraventricular nucleus of urethane anaesthetized rats every 1 s by differential pulse amperometry at + 105 mV combined with carbon fiber electrodes. In basal conditions, both extracellular noradrenaline and DOPAC, which are synthesized by noradrenergic terminals, contributed to this oxidation signal. Electrical stimulations of the rostral part of the A1 group were applied for 10 or 20 s every 10 min at physiological frequency (3-20 Hz). They induced an immediate increase in the oxidation signal which lasted as long as the stimulation. This increase was due to the evoked noradrenaline release since it was enhanced by pargyline, desipramine and amphetamine and it was attenuated by alpha-methyl-p tyrosine and reserpine. The amplitude of the evoked noradrenaline release depended non-linearly on the frequency of the stimulation (from 3 to 20 Hz). When expressed per pulse, noradrenaline release was facilitated four-fold as the frequency increased from 3 to 20 Hz. Central noradrenergic neurons exhibit a tonic activity in a single spike discharge pattern with a mean frequency below 5 Hz but they respond to physiological stimuli by short bursts of action potentials at 20 Hz. Therefore, the present data show that noradrenergic terminals convert physiological impulse flow into noradrenaline release as a high pass filter which enhances the signal-to-noise ratio in response to phasic stimuli. PMID- 2333152 TI - The secretion of catecholamines, chromogranin A and neuropeptide Y from the adrenal medulla of the cat via the adrenolumbar vein and thoracic duct: different anatomic routes based on size. AB - Secretion of the adrenal medulla was stimulated in nine cats by insulin-induced hypoglycemia. Levels of catecholamines (mol. wt 153-183), neuropeptide Y (mol. wt 4254) and chromogranin A (mol. wt 48,000) were measured in concurrently collected samples of adrenolumbar venous blood and thoracic duct lymph for up to 4 h following insulin administration. Insulin-induced hypoglycemia elicited an increase in the secretion of catecholamines, which reached peak levels in the adrenolumbar venous plasma at 1.5-2 h and in the lymph at 2.5 h. Although catecholamines were the most numerous measured molecules in the lymph, levels of norepinephrine and epinephrine were 75-250-fold less than those found in the adrenolumbar venous plasma. Neuropeptide Y in the adrenolumbar venous plasma reached peak levels between 1 and 1.5 h; at this time approximately 20% of the peak venous amount was detected in the lymph. Chromogranin A was found in approximately equal amounts in both plasma and lymph; the peak level in the plasma occurred at 1.5-2 h, while that in the lymph was reached at 2-3 h. We suggest that the size of a molecule influences the route it takes following exocytosis from the chromaffin vesicle. Smaller molecules such as catecholamines may pass directly into the circulation, while larger molecules such as chromogranin A may be temporarily sequestered in the interstitial space before passing into the lymph, and hence into the circulation. PMID- 2333153 TI - Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system. AB - A specific form of cytochrome P450, P450 IIE1, active in ethanol oxidation, is known to be induced about 10-fold in rat liver following ethanol treatment. This isozyme of P450 participates effectively in the metabolic activation of precarcinogens, such as N-dimethylnitrosamines, and of solvents such as carbon tetrachloride and benzene. In the present investigation, two different polyclonal antisera against P450 IIE1 were used in order to map the regional distribution of this P450 form in the rat central nervous system. The presence of P450 IIE1 in various brain regions was confirmed by Western blot analysis. The P450 IIE1 immunoreactivity was heterogeneously distributed between brain areas. Neuronal cell bodies and glial cells of presumed astroglial as well as oligodendroglial identity contained immunoreactivity. All fiber tracts harbored P450 IIE1 immunoreactive glial cells as did the ependymal lining of the ventricular wall as well as small and large vessels throughout the brain. P450 IIE1-immunoreactive glial cells were present in all areas of the neocortex, in the olfactory bulb, in the piriform cortex and in several different thalamic nuclei. In the cerebellum, P450 IIE-immunoreactivity was found in all cell layers and was exclusively localized to glial cells and their processes. Staining of blood vessels was prominent in the white matter where P450 IIE1-immunoreactive glial cells were seen to have end-feet on the vessels. A subgroup of pyramidal cells of the frontal cortex showed strong P450 IIE1-immunoreactivity, as did a component of the olfactory nerve which innervates the accessory bulb. In the hippocampal region, the pyramidal cells of all subfields were P450 IIE1-immunoreactive. Some polymorphic cells of the hilus and subfield CA stained intensely with the P450 IIE1 antibodies. A high density of P450 IIE1-immunoreactivity was detected throughout the striatal complex. The immunoreactivity was localized to neuronal cell bodies as well as the neurophil. Fibers of the nigrostriatal system were strongly P450 IIE1-immunoreactive. Mechanical lesions of this pathway showed an accumulation of P450 IIE1-immunoreactivity proximal to the lesion relative to the striatum and a depletion in the reticular part of the substantia nigra, suggesting that the antigen may be transported from the striatum to the substantia nigra. In the brain stem a high density of P450 IIE-immunoreactive neurons was detected in the substantia nigra, the pontine nucleus, lateral superior olive and the nucleus of the trigeminal nerve and facial nucleus. A great number of large- to medium-sized immunoreactive neurons were situated in the central gray and in the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2333154 TI - Ultrastructural localization of enkephalin-like immunoreactivity in developing rat cerebellum. AB - Methionine enkephalin, an endogenous opioid peptide, participates in the regulation of growth in the developing brain. In the present study, enkephalin like immunoreactivity was localized in the cerebellum of developing and adult rats by immunoelectron microscopy. In 10-day-old animals, enkephalin-like immunoreactivity was found in the somata of proliferating, migrating and differentiating neural cells, and was associated with the plasma membrane, microtubules, filaments, mitochondria, endoplasmic reticulum and nuclear envelope. Both neurons and glia in the cerebellum of the preweaning rat displayed a similar profile of immunoreactivity. Reaction product was also detected in the dendrites and dendritic spines of Purkinje cells where it was concentrated in postsynaptic densities. The majority of internal granule neurons in 10-day-old animals were not immunoreactive, nor were axons, glial processes and postsynaptic elements (with the exception of mossy fiber terminals). At weaning (Day 21), enkephalin-like immunoreactivity was confined primarily to the somata of Purkinje, basket and stellate neurons, and to Purkinje cell dendrites and synaptic spines. Adult rats (day 75) exhibited no enkephalin-like immunoreactivity. These results establish that enkephalin or an enkephalin-like substance can be detected during the ontogeny of both neurons and glia in the cerebellar cortex, and appears to be associated with certain structural elements. PMID- 2333155 TI - Green fluorescent latex microspheres: a new retrograde tracer. AB - The properties of a new fluorescent retrograde neuronal tracer, green fluorescent latex microspheres ("beads"), are described. Green beads, like the red beads that have been in use for several years, are readily transported by neurons in the mammalian central nervous system. After survival times ranging from 24 h to over one month they produce a distinct granular green fluorescence in the neuronal cytoplasm that is highly resistant to fading, when viewed using fluorescein filter sets. Green and red beads are transported with similar efficacy; cells labelled with either one or both tracers are easily distinguished. When injected into the brain, green beads, like red beads, show only minimal diffusion from the injection site. Because these two tracers differ only in their fluorescence, they should be ideal for double-labelling studies in a wide variety of systems and in developmental studies in which long-term retention of labels is required. PMID- 2333157 TI - Status epilepticus in perspective. A symposium. Chicago, April 12, 1989. Proceedings. PMID- 2333156 TI - The effect of muscle activity on motor unit size in partially denervated rat soleus muscles. AB - It has been shown previously that after section of L5 ventral ramus at 5 days the intact axons of L4 ventral ramus retain their large neonatal peripheral field in the rat soleus muscles. Soleus muscles of 5-day-old rats were partially denervated by section of their major neural input, L5 ventral ramus, and in addition paralysed with alpha-bungarotoxin for 3-5 days. The motor unit size was examined 2 months later. The tension developed by individual motor units from muscles that were partially denervated and in addition temporarily paralysed was much less than that after partial denervation alone. This reduced tension output was not due to muscle atrophy but to a smaller number of muscle fibres supplied by individual axons. Thus, unlike after partial denervation only, motoneurons were unable to maintain their large neonatal territory when the muscle was temporarily paralysed and they were unable to reoccupy this territory after the muscles recovered from the paralysis. The possibility that arrested muscle maturation due to paralysis has a permanent effect on motor unit size is discussed. PMID- 2333158 TI - The Department of Military Medicine--a graduate medical education idea whose time has come. PMID- 2333159 TI - The public health benefit of increasing tobacco taxes in New York State. AB - The 1989-1990 New York State budget increased the tax on a package of cigarettes from 21 to 33 cents. In this paper we estimate the impact of this tax increase on smoking prevalence and smoking-induced deaths in New York State. Findings show that 115,967 New Yorkers will be encouraged to quit or not start smoking as a result of the increased cigarette tax. The reduced prevalence of smoking attributed to the tax will result in the avoidance of approximately 28,992 premature smoking-induced deaths over the next generation. PMID- 2333161 TI - Children of substance abusers in New York State. PMID- 2333160 TI - Abdominal aortic aneurysmectomy without preoperative angiography. A prospective study. AB - In an attempt to analyze whether routine angiography is necessary prior to elective abdominal aortic aneurysmectomy (AAA), a prospective study was designed in which this examination was obtained only for specific indications. These included significant hypertension, renal dysfunction, symptoms of visceral ischemia, suprarenal extension of the aneurysm or a coexisting thoracic aneurysm, and diminished or absent femoral pulses. A consecutive series of 124 abdominal aortic aneurysms is reported, in which 110 procedures were performed electively. Preoperative angiograms were obtained in only ten patients (9.1%) and in nine of these an alteration in the usual operative strategy resulted. In the remaining 100 patients undergoing elective AAA without preoperative aortography, acceptable morbidity and mortality rates were obtained despite the intraoperative discovery of iliac aneurysms in 25 patients (23%) and accessory renal arteries in three patients (2.7%). In the absence of specific indications for angiography, the mainstay of the preoperative evaluation for abdominal aortic aneurysms should be computed tomography (CT). The preoperative workup can be done entirely on an outpatient basis. PMID- 2333162 TI - Churg-Strauss syndrome. PMID- 2333163 TI - Passover matzoh and chocolate Easter eggs. PMID- 2333164 TI - Superior vena cava syndrome associated with a Hickman catheter. PMID- 2333165 TI - Paraesophageal hernia. PMID- 2333166 TI - Animal experimentation for medical research. PMID- 2333167 TI - Lead poisoning during home renovation. PMID- 2333168 TI - Tumor metastasis to an infusaport site. PMID- 2333169 TI - Visual hallucinations as grief reaction without the Charles Bonnet syndrome. PMID- 2333170 TI - [Perinatal death]. PMID- 2333171 TI - [Reducing the severity of otitis media and acute bronchitis]. PMID- 2333172 TI - [Computerization. A structured approach for the nurse]. PMID- 2333173 TI - [Insomnia in the elderly]. PMID- 2333174 TI - [Hydrotherapy in obstetrics]. PMID- 2333175 TI - Informed consent. PMID- 2333176 TI - Eye protection in dental practice. AB - A survey of Southland dental practices showed that eye protection for dentists, dental surgery assistants, and patients did not generally meet currently recommended standards. The prevalence of eye injuries was low but, because of the random nature of many eye injuries, all practitioners should maintain proper protective procedures. PMID- 2333177 TI - A lingual mucogingival problem associated with ankyloglossia: a case report. AB - This report reviews the relationship between lingual frena, gingival recession, and tongue-tie, and describes a man with tongue-tie, localised gingival recession, and a speech impediment. The patient was treated surgically, with a satisfactory result 11 years later. PMID- 2333178 TI - A commitment to accountability. PMID- 2333179 TI - Nurses' Act review: draft policy input. PMID- 2333180 TI - Enrolled nurses convention 1990. PMID- 2333181 TI - Employment equity: an important issue for nurses. PMID- 2333182 TI - An Australian model. PMID- 2333183 TI - Sharpening the dull axe. Nursing and the clinical specialist. PMID- 2333184 TI - Racing toward the millennium. PMID- 2333185 TI - Socialized medicine and Chrysler. PMID- 2333186 TI - The real cost of eye exams. PMID- 2333187 TI - The cholesterol wars. PMID- 2333188 TI - Against Canadian health-care. PMID- 2333190 TI - Detecting AIDS earlier. PMID- 2333189 TI - Challenges from the Health Care Financing Administration. PMID- 2333191 TI - The Wehby Technique: a safer auscultatory method. PMID- 2333192 TI - Future looks bright for new lenses. PMID- 2333193 TI - Biliary lithotripsy. PMID- 2333194 TI - Resection of hepatic metastases of colorectal carcinoma. PMID- 2333195 TI - Perioperative red cell transfusion. PMID- 2333196 TI - Nonendocrine theories of the etiology of benign breast disease. PMID- 2333197 TI - Diagnostic peritoneal lavage vs. CT scanning in blunt abdominal trauma. PMID- 2333198 TI - The diet dilemma. PMID- 2333199 TI - Reading between the lines. PMID- 2333200 TI - Dieter's guide to dining out (or how to give your patients a conscience). PMID- 2333201 TI - Dieters seek newest seal of approval. PMID- 2333202 TI - Eosinophilia-myalgia syndrome: what is its link to L-tryptophan? PMID- 2333203 TI - Gallstone dissolution agents. PMID- 2333204 TI - Extracorporeal shock wave lithotripsy for gallstones. PMID- 2333205 TI - Falstaff obesity. PMID- 2333206 TI - The perils of telephone diagnosis. PMID- 2333207 TI - Arthroscopic surgery for treatment of temporomandibular joint hypomobility after mandibular sagittal osteotomy. AB - Arthroscopic surgery is an effective method for treating painful hypomobility of the temporomandibular joint. Decreased range of motion after sagittal ramus osteotomies of the mandible has been reported. Causes may include intra-articular factors. These cases may be effectively treated with arthroscopic lysis and lavage after failure of nonsurgical modalities. A series of 15 patients is presented. PMID- 2333208 TI - Large exostosis of the mandibular coronoid process. Report of a case. AB - The clinical experience of a patient with a large exostosis who had a chief complaint of difficulty in opening the mouth is reported. Radiographic examinations, especially tomography and a CT scan, were useful in the diagnosis. Surgical removal is the treatment of choice. The lesion is usually approached by a combination of intraoral and buccal routes; we also employed such an approach in this particular case. PMID- 2333209 TI - Too much marketing of new products. PMID- 2333210 TI - An unusual presentation of chronic graft-versus-host disease in an unrelated bone marrow transplantation. AB - The case described is that of an unrelated bone marrow transplantation in a 43 year-old man. Although the major histocompatibility complex met the criteria for a perfect genotypic match, de novo graft-versus-host disease developed with unusual manifestations involving structures of the oral cavity and associated areas. The loss of taste and smell, as well as profound xerostomia, was treated by stimulating salivary flow. Synergistic sialagogues were used with the hope that an increase in salivary production would mediate an improvement in taste and smell. PMID- 2333211 TI - Effect of dental plaque control on gingival lichen planus. AB - Eleven patients, all women, aged 43 to 76 years, with atrophic or ulcerative lichen planus lesions of gingiva were included in this preliminary study. After initial examination, the patients received an intensive individual hygiene treatment. The patients continued using the most appropriate, atraumatic method resulting in the best possible oral hygiene over a 1 year period during which they were seen for follow-up examinations at 3-month intervals. The mean plaque scores decreased after the initial treatment followed by an increase. The mean scores for severity of subjective symptoms and for type and extension of lesions initially decreased with the plaque scores and remained lower throughout the study. It is concluded that in some cases both subjective and objective improvement of atrophic and ulcerative gingival lichen planus may be obtained by means of intensive oral hygiene procedures although such procedures do not remove the basic cause of lichen planus. However, further studies are needed to examine the role of dental plaque control in patients with oral lichen planus. PMID- 2333212 TI - Self-healing traumatic bone cysts. AB - The etiology and pathogenesis of traumatic bone cyst are still far from being conclusively established with multiple theories, names, and forms of management being proposed and used. The rarity of these lesions in the older age groups suggests that self-healing can occur. This article presents two well-documented cases of what clinically and radiographically were consistent with so-called "traumatic bone cyst" of the mandible, which have appeared to heal without surgical intervention, thus providing additional information to our understanding of the biologic nature of this entity. Case 1 involved a 14-year-old boy with a lesion of the anterior left mandible that was monitored for 7 years and 5 months. Case 2 involved a 19-year-old female patient with a lesion of the right mandible that was monitored for 2 years and 9 months. In both cases, intraosseous biopsy or other surgical procedures were not undertaken. By the time both patients approached age 22, their lesions had resolved and the trabecular bone pattern radiographically approached normal. PMID- 2333213 TI - Spitz nevus of the palate. Report of a case. AB - A 4-year-old Japanese girl with a nonpigmented nodule on the anterior portion of the palate since birth is described. The overall microscopic appearance of the lesion was very similar to that of Spitz nevus of the skin. Diagnosis of Spitz nevus (mixed epithelioid cell and spindle cell nevus) was made on the basis of the clinical and histologic criteria for differentiating this lesion from malignant melanomas and common compound nevi. Positive immunostaining of epithelioid and spindle cells for S-100 protein and neuron-specific enolase was also indicative of their nevocellular nature. Review of the cases of Spitz nevus from the literature revealed that the present case most probably represents the first reported instance of this type of nevus in the oral cavity. PMID- 2333214 TI - Carcinoma of the lower lip with perineural extension to the middle cranial fossa. AB - An 81-year-old man had left labial paresthesia and a palpable mass adjacent to the left mental foramen 6 months after apparent adequate excision of a small (1.5 cm) primary squamous cell carcinoma of the left portion of the lower lip. Biopsy and clinical evaluation revealed recurrent squamous cell carcinoma. Subsequent left hemimandibulectomy confirmed perineural extension of tumor along the mandibular branch of the trigeminal nerve to the foramen ovale. Seven months later, the patient died of complications resulting from intracranial extension of tumor to the left cerebellopontine angle. This case illustrates the lethal potential of carcinoma of the lip due to contiguous perineural extension, even with a small primary tumor and absence of regional lymph node metastases. PMID- 2333215 TI - Orientation and eruptive patterns of the mandibular second premolar. AB - Distal migration of the mandibular second premolar into a first molar extraction site is a clinical finding often correlated with the early loss of a permanent mandibular first molar. Signs of this tendency can be detected radiographically as early as 6 to 7 years of age when the mineralization of the crown of the mandibular second premolar is almost complete. The results of a study of 2000 panoramic dental radiographs of children, aged 8 to 18 years, are reported. PMID- 2333217 TI - Fusion and gemination in alternate dentitions. PMID- 2333216 TI - The anterior buccal mandibular depression: physical and radiologic features. AB - The anterior buccal mandibular depression (ABMD), an anatomic variation not previously mentioned in the dental literature, is considered. Its physical and radiologic configuration is evaluated, and its significance in the differential diagnosis of radiolucent lesions in the anterior portion of the mandible is discussed. The general prevalence of ABMD was found to be 19.8%, with a significantly higher prevalence in children (p less than 0.001). In the majority of cases, the depression was radiologically detected. The radiopacity of the area was significantly dependent on depth of the depression (p less than 0.001). The radiographic image of the ABMD resembles, in many cases, the image of the less common anterior lingual salivary gland depression. The relatively high frequency of the ABMD indicates the importance of recognizing its radiologic features. PMID- 2333218 TI - Gemination of a maxillary premolar. PMID- 2333219 TI - Fusion of confusion? PMID- 2333220 TI - A case of extreme microdontia. PMID- 2333221 TI - Invaginated tooth associated with periodontal abscess. PMID- 2333222 TI - Mycobacterium avium complex tenosynovitis of the index finger. AB - A rare case of tenosynovitis of the right index finger caused by Mycobacterium avium complex is reported. A high index of suspicion resulted in early culture based diagnosis. Surgical synovectomy combined with a prolonged course of antituberculous medications resulted in normal hand function. PMID- 2333223 TI - Comparison of ultrasonically applied vs. intra-articular injected hydrocortisone levels in canine knees. AB - Phonophoresis of hydrocortisone is a commonly performed treatment for a wide variety of soft-tissue as well as intra-articular musculoskeletal disorders. There have been no previously reported studies indicating the degree of hydrocortisone penetration into joints achieved by means of phonophoresis. Twenty four purebred greyhounds were used to compare intra-articular levels of hydrocortisone resulting from intra-articular injection, phonophoresis, and external application of hydrocortisone. A total of 40 samples from canine knees were analyzed by means of fluorescence polarization. Intra-articular hydrocortisone levels obtained with phonophoresis were extremely low in comparison with those obtained with intra-articular injection. There were no statistically significant differences in intra-articular hydrocortisone levels between the phonophoresis and external application treatments, or between either of these and placebo control measurements taken from knees of untreated dogs and from shoulders of treated dogs. It appears that phonophoresis is an ineffective method of obtaining hydrocortisone penetration into a joint in the canine model. PMID- 2333224 TI - Tips of the trade #23. Simplified iliac crest cancellous grafting. AB - When fractures require small amounts of cancellous bone graft for healing but do not permit local bone harvesting, a simple percutaneous method may be used to obtain the graft from iliac crest. Using a winged iliac crest trephine (or any iliac crest biopsy trocar), the technique described is effective and markedly decreases morbidity. PMID- 2333225 TI - Compilation of small RNA sequences, 1990. PMID- 2333227 TI - A comprehensive list of cloned human DNA sequences. AB - A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID- 2333226 TI - Codon usage tabulated from the GenBank genetic sequence data. PMID- 2333228 TI - 'Wishing you well'. PMID- 2333229 TI - A need for nurture. PMID- 2333230 TI - Food for thought. PMID- 2333231 TI - DySSSy heights. PMID- 2333232 TI - Beyond the eleventh hour. PMID- 2333233 TI - The placebo effect. Magic pills. PMID- 2333234 TI - A plan for life. PMID- 2333235 TI - 1992. Is it all just talk? PMID- 2333236 TI - A cautionary tale. PMID- 2333237 TI - Fair deal on appeal. A hard day's night. PMID- 2333238 TI - Education. In need of qualification. PMID- 2333239 TI - Solving an age old problem. PMID- 2333240 TI - Essentials of management. Creating a climate for learning. PMID- 2333241 TI - Postoperative surgical wound infection. PMID- 2333243 TI - Ritual understanding of pregnancy and delivery. PMID- 2333242 TI - Community screening of elderly patients. PMID- 2333244 TI - 'Healthy localities'. PMID- 2333245 TI - RCN/BMA AIDS conference cardiff. Primary health care must 'mobilise against AIDS'. PMID- 2333246 TI - From Barnet to Jerusalem. Interview by Ann Goldberg. PMID- 2333247 TI - The crucial role of nurses in primary health care. PMID- 2333248 TI - Eradication of leprosy. The role staff nurses can play. PMID- 2333249 TI - Trichobezoar. A nursing care study. PMID- 2333250 TI - The health information resource network. A perspective report. PMID- 2333251 TI - Stress and coping among psychiatric nurses. PMID- 2333253 TI - Role of a clinical supervisor. PMID- 2333252 TI - The other side of abortion. PMID- 2333254 TI - Orthopedic surgery in New Zealand. PMID- 2333255 TI - Evaluation of hip pain following cemented total hip arthroplasty. AB - The occurrence of pain following a technically satisfactory cemented total hip arthroplasty is of concern for both the orthopedic surgeon and the patient. In order that the source of the pain be accurately located, a scientific approach is required. We present an algorithm for the evaluation of pain following an apparently satisfactory hip arthroplasty which, if followed, results in the correct diagnosis. PMID- 2333256 TI - Disability following fractures of the tibial shaft. PMID- 2333257 TI - Synovium transplantation onto the cartilage denuded patellar groove of the sheep knee joint. AB - A macroscopic and histologic study has been made on the changes during a 2-year period in a free composite graft of synovium subsynovial fat and periosteum taken from the medial femoral condyle and placed on the cartilage denuded patellar groove of the knee joint in skeletally mature sheep. The results have been compared to a control group which had the same surgical management except that the graft was discarded. The study demonstrated that following "take" and revascularization, the composite graft had converted to a single layer of vascular fibroblastic tissue by 6 weeks and over the ensuing year this had been largely replaced by fibrocartilage of variable differentiation. However, over the next year much of this fibrocartilage would appear to have undergone either redifferentiation into disorganized fibrochondroid tissue or developed secondary degenerative changes. By contrast, the control specimens had profound resorption of the bone plate followed by patchy resurfacing with tissue ranging from a very loose fibrous connective tissue to well differentiated fibrocartilage. The latter had gradually increased in amount of over the 2-year period, but secondary degenerative changes had also developed as in the grafted group. Despite some of the drawbacks, particularly the magnitude of the patello-femoral compression force, the technique has now been refined into a reliable animal model for the study of different parameters either in the graft or the graft environment in the hope that a way can be found to increase the life span of the metaplastic cartilage. PMID- 2333259 TI - Delayed open reduction and internal fixation of a displaced radiocapitellar fracture. PMID- 2333258 TI - Olecranon fracture with ipsilateral closed radial shaft fracture in a child with open epiphysis. PMID- 2333260 TI - Perthes-like disease and the tricho-rhino-phalangeal syndromes: the first black patient. AB - The TRPS I has been reported in European, Asian, Australian, and North American populations. To the best of our knowledge, this is the first case reported in the black population. Like many patients with this syndrome, it was the presence of "Perthes-like" disease that eventually lead to the diagnosis. This hip complication is very common, and often bilateral. A review of the literature stresses the importance of early diagnosis in that many patients are presenting late with severe degenerative arthritis. When present, "Perthes-like" changes should direct the observer to look for the abnormal hair and facies that are typical of these syndromes. Radiographs of the hands should also be obtained which will usually reveal the characteristic cone-shaped epiphyses. Clinical or radiographic evidence of multiple cartilaginous exostoses is diagnostic of TRPS II in the presence of other stigmata of the tricho-rhino-phalangeal syndrome (TRPS I). PMID- 2333261 TI - Transient osteoporosis of the hip. PMID- 2333262 TI - Problems of total hip replacement. PMID- 2333263 TI - Social medicine. PMID- 2333264 TI - Self-medication and alternative prescribing. PMID- 2333266 TI - Safe practice in repeat prescribing. PMID- 2333265 TI - Complementary therapies for common conditions. PMID- 2333267 TI - 'Working for patients' and inequalities in health care. PMID- 2333268 TI - A child with nocturnal cough. PMID- 2333269 TI - Diabetic clinics: how to run one. PMID- 2333270 TI - Ocular trauma. PMID- 2333271 TI - Requirements for drug monitoring of verapamil: experience from an unselected group of patients with cardiovascular disease. AB - Serum verapamil and metabolite concentrations were determined by HPLC in 29 patients in routine treatment with verapamil, and 23 were in steady state. Dosage levels and corresponding mean trough levels (+/- S.D.) were as follows: 120 mg daily: 79.1 (+/- 77) nmol/l, 240 mg daily: 173.3 (+/- 200.1) nmol/l, 360 mg daily: 204 (+/- 110.2) nmol/l and 480 mg daily: 361.0 (+/- 231.4) nmol/l. The variation coefficients were 97.3, 115.4, 54.0, and 62.1, respectively, thus showing considerable interpatient variation. Repeated determination of trough levels showed, in contrast, only small intrapatient variation (variation coefficient 35.8, 1.9, and 7.4, at the dosage levels 120, 240 and 340 mg per day). No significant correlation was found between serum verapamil levels age, sex, or weight. No significant effect of digoxin on the concentration of serum verapamil was found. No relation was observed between serum verapamil concentrations and desired effect or side-effects. Two patients showed no measurable serum verapamil, but one of these had detectable levels of metabolites. Such patients may represent subgroups of fast metabolizers or non absorbers. Measurements of the metabolites nor-verapamil, D 620 and D 617 indicated saturation of the first-pass metabolism. In conclusion, therapeutic drug monitoring is not indicated during routine verapamil treatment, whereas single measurements of verapamil may be warranted in patients not responding to treatment in order to identify fast metabolizers or non-absorbers. PMID- 2333272 TI - Further studies on the high-affinity binding of 3H-alaproclate to membranes from rat liver and some other tissues. AB - The high affinity binding of 3H-alaproclate to membranes in liver homogenates from naive rats and those treated with phenobarbital sodium, 75 mg/kg intraperitoneally, alaproclate hydrochloride, 40 mg/kg intraperitoneally proadifen hydrochloride, 40 mg/kg intraperitoneally once daily for 7 days and killed 24 hr after the last injection was examined. The treatment increased the normal number of alaproclate binding sites (Bmax: 1.1 nmol/g tissue, KD: 0.6 nM) by factors of about 10, 4 and 6, respectively. About 80% of the binding was localized to the microsomal fraction in both normal and phenobarbital treated rats. Ninety % of the alaproclate displaceable binding in a microsomal preparation of the normal liver was inhibited by low (nM) concentrations of proadifen whereas only about 20% in the liver preparations from phenobarbital treated rats was inhibited by low concentrations of proadifen. Thus, the main part of the induced binding sites was insensitive to proadifen. The same was found for the alaproclate and proadifen-induced alaproclate binding sites. The stereoselectivity of alaproclate enantiomers for binding to the normal and the induced binding sites was different: the S-(-) form was 100 times more potent than the R-(+)- enantiomer in inhibiting binding of racemic alaproclate to the normal sites, whereas the latter form was 3 times more potent than the former in inhibiting the binding to the phenobarbital-induced proadifen insensitive binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333273 TI - Effect of o,p'-DDD on the in vivo incorporation of 3H-thymidine into DNA: evidence for induced cell proliferation in the mouse lung. AB - The effects of o,p'-DDD on the DNA synthesis in the C57Bl mouse lung and liver were studied. As determined by 3H-thymidine incorporation into DNA, a selective increase in the lung DNA synthesis (+59%) was observed 2 days after a single intraperitoneal injection of 100 mg/kg o,p'-DDD. Microautoradiography showed that the incorporated 3H-thymidine was confined to a restricted number of heavily labelled cells, presumably proliferating type II cells. At the most, a 9 times higher rate of cell proliferation was observed in the lung 4 days after an intraperitoneal injection of 500 mg/kg o,p'-DDD. Using mouse lung or liver S-9 as activating system, no mutagenic activity of o,p'-DDD was detected in the Ames test. The induced cell proliferation may indicate a tissue-selective promoter activity of o,p'-DDD in the mouse lung. PMID- 2333274 TI - Effects of ethanol on expiratory neuronal activities in decerebrated cats. AB - The effects of ethanol on two types of bulbar expiratory neurones, post inspiratory (early expiratory) and expiratory (late expiratory) neurones, were studied in decerebrated, paralyzed and artificially ventilated cats. Intravenous injection of ethanol (300 mg/kg) depressed the efferent activity in the phrenic and recurrent laryngeal nerves which displayed the augmenting discharge during inspiration and the decrementing discharge during the early stage of expiration (stage I expiration). It reduced the duration of expiration, with a preferential effect on stage I expiration. Out of 22 medullary respiratory neurones consisting of 14 post-inspiratory and 8 expiratory neurones, 12 neurones were depolarized by ethanol and 10 neurones were hyperpolarized. In both cases, the respiratory fluctuations of membrane potential diminished and synaptic noises decreased. Input resistances of these neurones remained unchanged. Ethanol depressed the spike activity during stage I expiration of the post-inspiratory neurones. In expiratory neurones, a suppression of firing was greater in stage I expiration than in later stages of expiration. The present results demonstrate that ethanol reduces the expiratory period mainly through the depression of the post inspiratory neuronal activity in the bulbar respiratory control mechanism. PMID- 2333275 TI - Depressant effects of L-tyrosine on isolated perfused rat and rabbit hearts. AB - Tyrosine exerts potent cardiovascular effects: smaller doses induce tachycardia and hypertension while higher doses induce bradycardia and hypotension. However, the direct cardiac effects of this amino acid have not been characterised. In the present study increasing doses of L-tyrosine were administered to the perfusate of isolated rat (0.01-10.0 mg) and rabbit (0.5-40.0 mg) hearts. Heart rate and isometric force of contraction or amplitude of contractions, and either perfusion pressure or flow of perfusate were recorded. In rat hearts L-tyrosine decreased heart rate and isometric force of contraction. In rabbit hearts L-tyrosine also decreased heart rate and amplitude of contractions. The effects on coronary vasculature were variable. In rat hearts, high doses of L-tyrosine induced bi phasic changes with initial coronary dilatation, followed by vasoconstriction. In rabbit hearts the predominant effect of L-tyrosine was coronary artery constriction. These results show that the inhibitory cardiovascular effects of L tyrosine in vivo may be at least in part, explained by direct cardiac effects of this amino acid. PMID- 2333276 TI - Relation of Ca++ accumulation and lipid peroxidation with CCl4-induced toxicity in the rat liver. AB - The relationship between lipid peroxidation and Ca++ content in liver and hepatic cellular disruption was studied in 24 hr-fasted rats. Microsomal lipid peroxidation of livers in rats treated with a single dose of 16 mg or 96 mg CCl4/kg was significantly increased by 22% or 49% as measured by the diene conjugation technique. Ca++ content of liver microsomes in rats treated with 96 mg CCl4/kg was significantly increased by 20%, while the Ca++ content in rats treated with 16 mg CCl4/kg was not changed. On the other hand mitochondrial Ca++ content was tremendously increased in both rats treated with 16 mg and 96 mg CCl4/kg. Furthermore, when the activity of plasma glutamic pyruvic transaminase (GPT), which is a liver-specific enzyme, was investigated 3 hr after CCl4 treatment, hepatotoxicity was evident in rats treated with 96 mg/kg but not evident in rats treated with 16 mg/kg. These results indicate that there was a good correlation between the microsomal Ca++ content and the hepatic cellular disruption but no correlation between the microsomal lipid peroxidation and the hepatic cellular disruption as measured by the diene conjugation. PMID- 2333277 TI - Prolonged action potential duration of guinea-pig heart muscle after pethidine. AB - Since recent experiments indicated class III antiarrhythmic properties of pethidine in vitro, we studied cardiac effects of pethidine in vivo. Monophasic action potentials at different pacing rates were recorded from the left ventricular epicardium of pentobarbital anaesthetized guinea-pigs by means of suction electrode catheter. Intravenous injection of pethidine 2 mg/kg prolonged the action potential duration, and increased left ventricular developed pressure and dP/dt max, compared to animals receiving saline only. It is concluded that pethidine appears to have class III antiarrhythmic properties. PMID- 2333279 TI - The distribution of multiple doses of pentamidine in rats. PMID- 2333278 TI - Comparative studies of the effects on liver and liver microsomal drug metabolizing enzyme system by the fungicides captan, captafol and folpet in rats. PMID- 2333280 TI - Disposition of morphine-3-glucuronide in the pregnant rhesus monkey. AB - Morphine-3-glucuronide (M3G) is the major metabolite of morphine and is present in the circulation of persons treated with morphine or abusing heroin. This project was designed to study the kinetics of M3G in the foeto-maternal compartment, since this metabolite may be of relevance for the abstinence syndrome observed in neonates of pregnant abusers. The kinetics of M3G were studied in two non-pregnant and four pregnant Rhesus monkeys. M3G was given as a bolus injection in four of the animals and as a long-term infusion for 12 hr in two animals. M3G passed slowly across the placenta to the foetus and amniotic fluid. After 10 hr of M3G infusion, the foetal plasma M3G concentration was measured in two cases and found to be 37% and 72%, respectively, of the maternal concentration. PMID- 2333281 TI - Isolation of fetal DNA from nucleated erythrocytes in maternal blood. AB - Fetal nucleated cells within maternal blood represent a potential source of fetal genes obtainable by venipuncture. We used monoclonal antibody against the transferrin receptor (TfR) to identify nucleated erythrocytes in the peripheral blood of pregnant women. Candidate fetal cells from 19 pregnancies were isolated by flow sorting at 12 1/2-17 weeks gestation. The DNA in these cells was amplified for a 222-base-pair (bp) sequence present on the short arm of the Y chromosome as proof that the cells were derived from the fetus. The amplified DNA was compared with standardized DNA concentrations; 0.1-1 ng of fetal DNA was obtained in the 20-ml maternal samples. In 7/19 cases, a 222-bp band of amplified DNA was detected, consistent with the presence of male DNA in the isolated cells; 6/7 of these were confirmed as male pregnancies by karyotyping amniocytes. In the case of the female fetus, DNA prepared from samples at 32 weeks of gestation and cord blood at delivery also showed the presence of the Y chromosomal sequence, suggesting Y sequence mosaicism or translocation. In 10/12 cases where the 222-bp band was absent, the fetuses were female. Thus, we were successful in detecting the Y chromosomal sequence in 75% of the male-bearing pregnancies, demonstrating that it is possible to isolate fetal gene sequences from cells in maternal blood. Further refinement in methodology should increase sensitivity and facilitate noninvasive screening for fetal gene mutations. PMID- 2333282 TI - Molecular characterization and biological function of the movement protein of tobacco mosaic virus in transgenic plants. AB - We previously demonstrated, in transgenic tobacco plants, that the role of the movement protein (MP) of tobacco mosaic virus is to facilitate the cell-to-cell spread of viral progeny during infection. An analysis of different tissues of these transgenic plants indicated that the MP accumulated in leaf, stem, and root tissue. The highest levels were detected in older leaves. The relative levels of MP in leaf tissue from transgenic plants were equivalent to, or higher than, the levels of MP in tobacco mosaic virus-infected leaf tissue. Results of subcellular fractionation of homogenates of transgenic leaf tissue showed that the MP was most abundant in the cell wall fraction of older leaves and that the protein remained at high levels in the cell wall fraction as the leaves continued to age. Significant levels of the MP were detected in a crude membrane/organelle fraction and a soluble fraction in younger leaves but decreased to low levels in older leaves. These results suggest that the MP accumulates and is stable in cell walls. We have previously shown that the MP modifies the molecular exclusion limit of plasmodesmata, which is consistent with the hypothesis that plant viruses move from cell to cell through altered plasmodesmata. We show here that the ability of the tobacco mosaic virus MP to modify the molecular exclusion limit of plasmodesmata in tobacco depends on the developmental stage of the leaf. The implications of these findings on understanding virus movement and how plasmodesmata function are discussed. PMID- 2333284 TI - Agonist-induced ADP-ribosylation of a cytosolic protein in human platelets. AB - alpha-Thrombin and phorbol 12,13-dibutyrate stimulated the mono(ADP-ribosyl)ation of a 42-kDa cytosolic protein of human platelets. This effect was mediated by protein kinase C activation and was inhibited by protein kinase C inhibitor staurosporine. It also was prevented by prostacyclin, which is known to inhibit the phospholipase C-induced formation of 1,2-diacylglycerol, which is one of the endogenous activators of protein kinase C. On sodium dodecyl sulfate/polyacrylamide gel electrophoresis, the 42-kDa protein that is ADP ribosylated by alpha-thrombin was clearly distinct from the alpha subunits of membrane-bound inhibitory and stimulatory guanine nucleotide-binding regulatory proteins, respectively Gi alpha and Gs alpha; the 47-kDa protein that is phophorylated by protein kinase C in platelets; and the 39-kDa protein that has been shown to be endogenously ADP-ribosylated by agents that release nitric oxide. This information shows that agonist-induced activation of protein kinase leads to the ADP-ribosylation of a specific protein. This covalent modification might have a functional role in platelet activation. PMID- 2333285 TI - Interleukin 6 dependence of spontaneous in vitro differentiation of B cells from patients with IgM gammapathy. AB - Blood B cells from eight patients with clonal lymphoid disorders characterized by monoclonal IgM secretion (four with malignant plasmacytic proliferation typical of Waldenstrom macroglobulinemia and four without overt lymphoid neoplasia) were found to spontaneously differentiate in vitro into plasma cells. In all instances, monoclonal plasma cells (8-45% of the cells) were generated from extensively purified B cells or T-cell-depleted peripheral blood mononuclear cells after a 7-day culture period, with a corresponding high rate of IgM secretion into the culture medium. This differentiation occurred in the absence of any cell proliferation process as measured by [3H]thymidine uptake at day 2 or 4. Normal B cells did not differentiate under the same experimental conditions. Detection of interleukin 6 (IL-6) bioactivity in all patients' B-cell culture supernatants as well as of IL-6 mRNA in freshly prepared, uncultured B cells in the two cases studied by in situ hybridization suggested that IL-6 secretion by B cells may play a role in this process. Moreover, in the four patients without overt lymphoid proliferation, B-cell differentiation was significantly inhibited (60-80%) in the presence of anti-IL-6 antibodies. In contrast, anti-IL-6 antibodies did not preclude the differentiation into plasma cells of B cells from the four patients with bona fide Waldenstrom macroglobulinemia. These results suggest a two-step pathogenesis for such human lymphoplasmacytic clonal proliferations, the initial stage being characterized by an IL-6-dependent autocrine differentiation pathway. PMID- 2333283 TI - Cell-cell adhesion mediated by binding of membrane-anchored transforming growth factor alpha to epidermal growth factor receptors promotes cell proliferation. AB - The precursor for transforming growth factor alpha, pro-TGF-alpha, is a cell surface glycoprotein that can establish contact with epidermal growth factor (EGF) receptors on adjacent cells. To examine whether the pro-TGF-alpha/EGF receptor pair can simultaneously mediate cell adhesion and promote cell proliferation, we have expressed pro-TGF-alpha in a bone marrow stromal cell line. Expression of pro-TGF-alpha allows these cells to support long-term attachment of an EGF/interleukin-3-dependent hematopoietic progenitor cell line that expresses EGF receptors but is unable to adhere to normal stroma. This interaction is inhibited by soluble EGF receptor ligands. Further, the hematopoietic progenitor cells replicate their DNA while they are attached to the stromal cell layer and become foci of sustained cell proliferation. Thus, pro-TGF alpha and the EGF receptor can function as mediators of intercellular adhesion and this interaction may promote a mitogenic response. We propose the term "juxtacrine" to designate this form of stimulation between adjacent cells. PMID- 2333286 TI - Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA. AB - Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, we identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair. PMID- 2333288 TI - High-level beta-globin expression after retroviral transfer of locus activation region-containing human beta-globin gene derivatives into murine erythroleukemia cells. AB - The locus activation region (LAR) of the human beta-globin-like gene cluster is characterized by a group of four DNase I hypersensitive sites, which arise specifically in erythroid tissues and are required for a normal pattern of beta globin-like gene expression. The hypersensitive sites are found at positions 6.1, 10.9, 14.7, and 18 kilobase pairs (kbp) 5' of the epsilon-globin gene. Recently functional assays of the LAR that tested determinants for all four hypersensitive sites showed that expression of the human beta-globin gene was increased to normal or near-normal levels in both transgenic mice and erythroid cells. We constructed retroviral vectors with a human beta-globin gene and the determinant for a single hypersensitive site and measured beta-globin gene expression after retroviral infection of murine erythroleukemia cells. Fragments for the hypersensitive sites at -18 or -10.9 kbp increased human beta-globin RNA levels respectively to 35% or 132% of the endogenous mouse beta maj-globin RNA level. In addition, greater expression was also observed for the neomycin phosphotransferase RNA, which was transcribed from the retroviral LTR, showing that the LAR fragments activated expression from a heterologous promoter. In the context of gene-transfer experiments ultimately aimed at gene therapy, our results show that LAR determinants lead to an increased level of human beta globin RNA expression after retroviral transfer into erythroid cells. But inclusion of LAR determinants in retroviral vectors also entails the potential risk of activating the expression of nonglobin genes in erythroid cells. PMID- 2333287 TI - Topography of toxin-acetylcholine receptor complexes by using photoactivatable toxin derivatives. AB - We have defined the molecular environment of a snake neurotoxin interacting with the high- and low-affinity binding sites of the nicotinic acetylcholine receptor (AcChoR). This was done by photocoupling reactions using three toxin derivatives with photoactivatable moieties on Lys-15, Lys-47, and Lys-51. Competition data showed that Lys-47 belongs to the toxin-AcChoR interacting domain whereas the other two residues are excluded from it. We first tentatively determined the threshold of covalent coupling, indicative of the proximity between the photoactivatable probes and subunits, by quantifying the coupling occurring between the same derivatives and a model compound (i.e., a toxin-specific monoclonal antibody). We then (i) quantified the coupling yields occurring when both binding sites of AcChoR were occupied by the toxin derivatives, (ii) discriminately quantified the coupling yields at the high-affinity binding site, and (iii) deduced the coupling yields at the low-affinity binding site. In the high-affinity site, the probes on Lys-15 and Lys-47 predominantly reacted with the high-affinity site of the AcChoR alpha subunit whereas the probe on Lys-51 reacted with the delta subunit. In the low-affinity site, the probe on Lys-47 predominantly reacted with the low-affinity site of the alpha chain and the beta chain whereas those on Lys-15 and Lys-51 reacted with the gamma and delta chains, respectively. A three-dimensional model showing a unique organization of AcChoR bound to two toxin molecules is presented. PMID- 2333289 TI - Mechanism of the selective functionalization of saturated hydrocarbons by Gif systems: relationship with methane monooxygenase. AB - Two intermediates, A and B, have been identified in the selective oxidation of saturated hydrocarbons to ketones by Gif-type systems. Intermediate A has been characterized as an Fev species with a secondary iron sigma-bond to carbon; it is captured by four different reagents or transformed into the second intermediate, B, which hydrolyzes to form a secondary alcohol. A mu-oxo Fe2III dimer is proposed as a basis for Gif-type reactivity. If the first iron is involved in the synthesis of intermediate A, the second is used to oxidize intermediate B intramolecularly to a ketal, which on hydrolysis yields a ketone. The enzyme methane monooxygenase shows a remarkable similarity to Gif-type systems in its selective hydrocarbon oxidation, particularly in the case of adamantane. PMID- 2333290 TI - Transferrin-polycation conjugates as carriers for DNA uptake into cells. AB - We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbumin, has been covalently linked to the small DNA-binding protein protamine or to polylysines of various sizes through a disulfide linkage. These modified transferrin molecules maintain their ability to bind their cognate receptor and to mediate efficient iron transport into the cell. The transferrin polycation molecules form electrophoretically stable complexes with double stranded DNA, single-stranded DNA, and modified RNA molecules independent of nucleic acid size (from short oligonucleotides to DNA of 21 kilobase pairs). When complexes of transferrin-polycation and a bacterial plasmid DNA containing the gene for Photinus pyralis luciferase are supplied to eukaryotic cells, high-level expression of the luciferase gene occurs, demonstrating transferrin receptor mediated endocytosis and expression of the imported DNA. We refer to this delivery system as "transferrinfection." PMID- 2333291 TI - HLA-B37 and HLA-A2.1 molecules bind largely nonoverlapping sets of peptides. AB - T-cell recognition of peptides that are bound and presented by class I major histocompatibility complex molecules is highly specific. At present it is unclear what role class I peptide binding plays relative to T-cell receptor specificity in determination of immune recognition. A previous study from our group demonstrated that the HLA-A2.1 molecule could bind to 25% of the members of a panel of unrelated synthetic peptides as assessed by a functional peptide competition assay. To determine the peptide-binding specificity of another HLA class I molecule, we have examined the capacity of this panel of peptides to compete for the presentation of influenza virus nucleoprotein peptide NP-(335 350) by HLA-B37 to NP-peptide-specific HLA-B37-restricted cytotoxic T-lymphocyte lines. Forty-two percent of peptides tested were capable of inhibiting NP-(335 350) presentation by HLA-B37. Remarkably, none of these HLA-B37-binding peptides belong to the subset that was previously shown to bind to the HLA-A2.1 molecule. Only the NP-(335-350) peptide was capable of binding to both HLA-A2.1 and HLA B37. These findings demonstrate that the peptide-binding specificities of HLA-B37 and HLA-A2.1 are largely nonoverlapping and suggest that, from the universe of peptides, individual HLA class I molecules can bind to clearly distinct subsets of these peptides. PMID- 2333292 TI - Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides. AB - Oligodeoxynucleotides (ODNs) were synthesized and tested for their antiviral activity against influenza viruses. ODNs corresponded to the polymerase PB1 gene of either influenza A/WSN/33 virus or influenza C/JJ/50 virus. All compounds were 20 nucleotides long, including control ODNs containing mismatches. The phosphodiester ODNs (O-ODNs) failed to inhibit replication of influenza A and influenza C viruses at concentrations up to 80 microM, possibly due to intracellular nuclease digestion of the unmodified oligomers. By contrast, the phosphorothioate derivatives (S-ODNs) were found to inhibit replication of both influenza A and influenza C virus. The antiviral effect of S-ODNs against influenza A virus was found at concentrations as low as 1.25 microM and was present with mismatched oligomers. In the case of influenza C virus, the S-ODN complementary to the 3' end of the viral RNA of the PB1 gene revealed a sequence specific antiviral activity at a concentration of 20 microM. (At the same concentration, S-ODNs with one or three mismatches showed little or no antiviral activity.) Reduction in plaque number reached six logarithms when this sequence specific S-ODN was used at a concentration of 80 microM. PMID- 2333293 TI - Human interleukin 2 receptor beta-chain gene: chromosomal localization and identification of 5' regulatory sequences. AB - Interleukin 2 (IL-2) binds to and stimulates activated T cells through high affinity IL-2 receptors (IL-2Rs). Such receptors represent a complex consisting of at least two proteins, the 55-kDa IL-2R alpha chain and the 70-kDa IL-2R beta chain. The low-affinity, IL-2R alpha chain cannot by itself transduce a mitogenic signal, whereas IL-2 stimulates resting lymphocytes through the intermediate affinity, IL-2R beta receptor. We report here identification of the genomic locus for IL-2R beta. The exons are contained on four EcoRI fragments of 1.1, 9.2, 7.2, and 13.7 kilobases. The 1.1-kilobase EcoRI fragment lies at the 5'-most end of the genomic locus and contains promoter sequences. The promoter contains no TATA box-like elements but does contain the d(GT)n class of middle repetitive elements, which may play an interesting regulatory role. The IL-2R beta gene is localized to chromosome 22q11.2-q12, a region that is the locus for several lymphoid neoplasias. PMID- 2333294 TI - Vertical transmission of human immunodeficiency virus is correlated with the absence of high-affinity/avidity maternal antibodies to the gp120 principal neutralizing domain. AB - Many, but not all, infants born to mothers infected with the human immunodeficiency virus (HIV) are infected in utero. We have now shown that mothers who have high-affinity/avidity antibodies directed toward the principal neutralizing domain (PND) of gp120 are less likely to transmit HIV to their children. An ELISA that preferentially measures the level of the biologically functioning, high-affinity/avidity antibodies against PND is described. In a retrospective study of 15 maternal/neonatal serum samples, the assay correctly identified the 4 uninfected and the 11 HIV-infected infants. Other clinical and laboratory parameters such as p24 antigen, phytohemagglutinin mitogenic index, and absolute surface antigen T4+ cell counts did not accurately predict HIV fetal transmission. In addition to introducing a promising diagnostic tool, this study provides the in vivo evidence that protective antibodies may prevent infection by HIV. PMID- 2333295 TI - K+ channel openers activate brain sulfonylurea-sensitive K+ channels and block neurosecretion. AB - Vascular K+ channel openers such as cromakalim, nicorandil, and pinacidil potently stimulate 86Rb+ efflux from slices of substantia nigra. This 86Rb+ efflux is blocked by antidiabetic sulfonylureas, which are known to be potent and specific blockers of ATP-regulated K+ channels in pancreatic beta cells, cardiac cells, and smooth muscle cells. K0.5, the half-maximal effect of the enantiomer ( )-cromakalim, is as low as 10 nM, whereas K0.5 for nicorandil is 100 nM. These two compounds appear to have a much higher affinity for nerve cells than for smooth muscle cells. Openers of sulfonylurea-sensitive K+ channels lead to inhibition of gamma-aminobutyric acid release. There is an excellent relationship between potency to activate 86Rb+ efflux and potency to inhibit neurotransmitter release. PMID- 2333297 TI - Metastability of the folded states of globular proteins. AB - The possibility that several metastable minima exist in which the folded forms of a polypeptide chain have similar structural characteristics but different energies is suggested. The validity of this hypothesis is illustrated with the aid of simulation methods on a model protein that folds into a beta-barrel structure. Some implications of this hypothesis such as the existence of multiple pathways with intermediates for protein folding are discussed. PMID- 2333298 TI - Structure of the anti-human immunodeficiency virus agent 3'-fluoro-3' deoxythymidine and electronic charge calculations for 3'-deoxythymidines. AB - The crystal and molecular structures of the anti-human immunodeficiency virus agent 3'-fluoro-3'-deoxythymidine have been determined by x-ray diffraction and stereochemical comparisons with thymidine have been made. Atomic charge distributions have been calculated by the complete neglect of differential overlap method for thymidine and antiretrovirally active and inactive C3' substituted analogues. The structural and electronic results suggest that antiviral activity in these analogues may be correlated with the presence of an electronegative atom attached to C3'. PMID- 2333296 TI - Mitogenic activity from trout embryos. AB - An extract of 21-day rainbow trout embryos stimulated growth of several piscine cell lines in the absence of added serum. Established lines from trout (RTG-2 and STE-137), salmon (CHSE-214), carp (EPC), and goldfish (CAR) and early-passage cells initiated from trout embryos grew in serum-free medium containing the embryo extract. In addition the extract was sufficient for maintaining long-term cultures of CHSE-214 cells for several months through a minimum of 20 passages (approximately 50 population doublings) in the absence of serum. Optimal response was achieved with 100 micrograms of extract protein per ml, but a significant growth-promoting effect was observed with as little as 2.5 micrograms/ml. The activity was nondialyzable, protease-sensitive, and stable in 200 mM acetic acid. The level of mitogenic response induced by the extract could not be duplicated with purified mammalian growth factors added individually or in combination, and the extract did not stimulate DNA synthesis in quiescent mouse fibroblasts. These results suggest that trout embryo extract may contain a novel growth-promoting activity for fish cells. PMID- 2333299 TI - Growth and atrophy of neurons labeled at their birth in a song nucleus of the zebra finch. AB - The robust nucleus of the archistriatum (RA) is one of the forebrain nuclei that control song production in birds. In the zebra finch (Poephila guttata), this nucleus contains more and larger neurons in the male than in the female. A single injection of tritiated thymidine into the egg on the 6th or 7th day of incubation resulted in labeling of many RA neurons with tritium. The size of tritium-labeled neurons and the tissue volume containing them did not differ between the sexes at 15 days after hatching. In the adult brain, tritium-labeled neurons and the tissue volume containing them were much larger in the male than in the female. Also, tritium-labeled RA neurons were large in females which received an implant of estrogen immediately after hatching. The gender differences in the neuron size and nuclear volume of the zebra finch RA are, therefore, due not to the replacement of old neurons by new ones during development but to the growth and atrophy of neurons born before hatching. Similarly, the masculinizing effects of estrogen on the female RA are due not to neuronal replacement but to the prevention of atrophy and promotion of growth in preexisting neurons. PMID- 2333300 TI - Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2. AB - Defined by monoclonal antibody GA733, the GA733-2 antigen is a cell surface 40 kDa glycoprotein associated with human carcinomas of various origins. Molecular clones for the GA733-2 antigen were isolated from a colorectal carcinoma cell line cDNA library using the high-efficiency COS cell expression system. A 1.4 kilobase cDNA species was enriched by immunoselection with monoclonal antibody. The authenticity of individual clones was established by immunologic and sequence criteria. At the amino acid sequence level, GA733-2 was found to be greater than 99% identical to the previously described KSA antigen defined by monoclonal antibody KS1/4. The amino acid sequence derived from the previously described GA733-related gene, GA733-1, was found to be 49% identical to GA733-2. The positions of 12 cysteine residues in the extracellular domains of the two GA733 antigens are conserved, as is the overall distribution of hydrophobic and hydrophilic residues. A 1.45-kilobase transcript of the GA733-2/KSA gene was found to be expressed in cell lines derived from colorectal and pancreatic carcinoma. PMID- 2333301 TI - The NO hypothesis: possible effects of a short-lived, rapidly diffusible signal in the development and function of the nervous system. AB - Several observations suggest that the Ca2(+)-dependent postsynaptic release of nitric oxide (NO) may be important in the formation and function of the vertebrate nervous system. We explore here the hypothesis that the release of NO and its subsequent diffusion may be critically related to three aspects of nervous system function: (i) synaptic plasticity and long-term potentiation in certain regions of the adult nervous system, (ii) the control of cerebral blood flow in such regions, and (iii) the establishment and activity-dependent refinement of axonal projections during the later stages of development. In this paper, we detail and analyze the basic assumptions underlying this NO hypothesis and describe a computer simulation of a minimal version of the hypothesis. In the simulation, a 3-dimensional volume of neuropil is presented with patterned afferent input; NO is produced, diffuses, and is destroyed; and synaptic strengths are determined by a set of synaptic rules based on the correlation of synaptic depolarization and NO levels. According to the hypothesis, voltage dependent postsynaptic release of this rapidly diffusing substance links the activities of neurons in a local volume of tissue, regardless of whether the neurons are directly connected by synapses. This property is demonstrated in the simulation, and it is this property that is exploited in the hypothesis to account for certain aspects of long-term potentiation and activity-dependent sharpening of axonal arbors. PMID- 2333302 TI - Defective ATP-dependent bile canalicular transport of organic anions in mutant (TR-) rats with conjugated hyperbilirubinemia. AB - TR- mutant Wistar rats secrete markedly fewer organic anions other than bile acids from the liver into the bile than do control rats. Fluorescence-image analysis of isolated normal and TR- hepatocyte "doublets", which retain a bile canaliculus between them, revealed that normal hepatocytes readily transport a fluorescent bile acid (fluorescein isothiocyanate glycocholate) and a nonbile acid organic anion (carboxydichlorofluorescein diacetate) into the canaliculus. Hepatocyte doublets from TR- rats also transported fluorescein isothiocyanate glycocholate normally, but transport of carboxydichlorofluorescein diacetate into the canaliculus was negligible. Vesicles derived from the canicular domain of the plasma membrane of hepatocytes (CMV) from control and TR- rats were used to characterize the transport process for 35S-labeled bromosulphthalein and 35S labeled bromosulphthalein glutathione, which represent nonbile acid organic anions. CMV from normal rat hepatocytes had an ATP- and temperature-dependent, saturable transport process for these 35S-labeled compounds that was absent in CMV from TR- rats. CMV from TR- rats retained normal ATP-dependent transport of daunomycin, and immunologic blots with a monoclonal antibody against the multidrug resistance gene product, P-glycoprotein, revealed no difference between normal and TR-CMV. These studies reveal that the bile canaliculus in normal rats contains an ATP-dependent organic anion transport system that is functionally absent in TR- mutant rats. The defect in TR- mutant rats is phenotypically similar to that seen in mutant Corriedale sheep and in the Dubin-Johnson syndrome in man. PMID- 2333303 TI - Fibronectin controls capillary endothelial cell growth by modulating cell shape. AB - An in vitro system has been developed to study the mechanism by which fibronectin (FN) regulates capillary endothelial cell growth in the presence of soluble angiogenic mitogens. Endothelial cells were cultured in chemically defined medium containing a constant, saturating amount of basic fibroblast growth factor. Formation of cell-FN contacts was then varied in a controlled fashion by three different techniques: (i) nonadhesive, bacteriological dishes were precoated with increasing densities of FN; (ii) soluble RGD peptides were used to progressively inhibit binding of cell-surface integrin receptors to adsorbed FN; and (iii) FN coated surfaces were covered with increasingly thick layers of polyhydroxyethylmethacrylate (a nonadhesive polymer) to physically restrict cell access to FN binding sites. Endothelial cells became more extended and proliferated more rapidly as FN coating concentrations were raised from approximately 250 to approximately 10,000 FN molecules per micron 2. Computerized morphometric analysis confirmed that cell shape (projected cell areas) was determined by the density of FN contacts and that DNA synthetic levels were tightly coupled to the extent of cell spreading, regardless of the method used to perturb cell adhesion. In contrast, neither soluble FN nor cell-surface binding of FN-coated microbeads (diameter, 4.5 microns) had any effect on growth when cells were grown in suspension and cell spreading was prohibited. These results suggest that FN controls capillary endothelial cell proliferation based on its ability to support tension-dependent alterations of cell shape--i.e., both by binding to cell-surface integrins and by resisting mechanical loads that are applied to these receptors. PMID- 2333304 TI - Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. AB - A major goal of current hematopoiesis research is to develop in vitro methods suitable for the measurement and characterization of stem cells with long-term in vivo repopulating potential. Previous studies from several centers have suggested the presence in normal human or murine marrow of a population of very primitive cells that are biologically, physically, and pharmacologically different from cells detectable by short-term colony assays and that can give rise to the latter in long-term cultures (LTCs) containing a competent stromal cell layer. In this report, we show that such cultures can be used to provide a quantitative assay for human "LTC-initiating cells" based on an assessment of the number of clonogenic cells present after 5-8 weeks. Production of derivative clonogenic cells is shown to be absolutely dependent on the presence of a stromal cell feeder. When this requirement is met, the clonogenic cell output (determined by assessment of 5-week-old cultures) is linearly related to the input cell number over a wide range of cell concentrations. Using limiting dilution analysis techniques, we have established the frequency of LTC-initiating cells in normal human marrow to be approximately 1 per 2 X 10(4) cells and in a highly purified CD34-positive subpopulation to be approximately 1 per 50-100 cells. The proliferative capacity exhibited by individual LTC-initiating cells cultured under apparently identical culture conditions was found to be highly variable. Values for the number of clonogenic cells per LTC-initiating cell in 5-week-old cultures ranged from 1 to 30 (the average being 4) with similar levels being detected in positive 8-week-old cultures. Some LTC-initiating cells are multipotent as evidenced by their generation of erythroid as well as granulopoietic progeny. The availability of a system for quantitative analysis of the proliferative and differentiative behavior of this newly defined compartment of primitive human hematopoietic cells should facilitate future studies of specific genetic or microenvironmental parameters involved in the regulation of these cells. PMID- 2333305 TI - Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation-response (TAR) element of human immunodeficiency virus. AB - Human immunodeficiency virus type 1 RNAs contain a sequence, trans-activation response (TAR) element, which is required for tat protein-mediated trans activation of viral gene expression. We have identified a nuclear protein from extracts of HeLa cells that binds to the TAR element RNA in a sequence-specific manner. The binding of this 68-kDa polypeptide was detected by UV cross-linking proteins to TAR element RNA transcribed in vitro. Competition experiments were performed by using a partially purified preparation of the protein to quantify the relative binding affinities of TAR element RNA mutants. The binding affinity of the TAR mutants paralleled the reported ability of those mutants to support tat trans-activation in vivo. We propose that this cellular protein moderates TAR activity in vivo. PMID- 2333307 TI - [Synthesis, characterization, racemation and biochemical studies on 10 acylderivatives of chrysarobin: sorbylchrysarobin, beta carbethoxypropionylchrysarobin and senecioylchrysarobin]. AB - The racemic synthesis of three 10-acylderivatives of chrysarobin (1) is described. Senecioylchrysarobin (3), beta-carbethoxypropionylchrysarobin (4) and sorbylchrysarobin (5) were prepared by reaction of (1) with the corresponding carboxylic acid chlorides and collidine as a base in toluene. The separation of the racemates of (3) and (5) on a chiral stationary phase is demonstrated for the first time. All of the new compounds showed an increased potency of inhibition of the enzyme glucose-6-phosphate dehydrogenase, an indication for possible antipsoriatic activity. PMID- 2333308 TI - [Chemical instability of the antipsoriatic dithranol and chrysarobin in aqueous systems: oxidation behavior]. AB - Decomposition of dithranol (1) and chrysarobin (4) in homogeneous and heterogeneous buffer solutions (pH 7.5) were studied by means of HPLC chromatography. Half lives of (1) under homogeneous conditions were 1 h 15 min., under heterogeneous conditions 2 h 45 min., whereas in the case of (4) 3 h and 30 min. respectively were measured. (1) was degraded to dihydroxyanthrachinon (2) and dimeric dithranol (3), the amount of (2) and (3) depending of the chosen conditions, whereas degradation of (4) under heterogeneous conditions revealed no oxidation products. On the other hand two metabolites of (4) were detected in homogeneous buffer solutions. The presenting studies clearly show the different ways of decomposition of (1) and (4) in homogeneous and heterogeneous solutions. PMID- 2333306 TI - NG-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. AB - Clinical assessment of the activity of tumor necrosis factor (TNF) against human cancer has been limited by a dose-dependent cardiovascular toxicity, most frequently hypotension. TNF is also thought to mediate the vascular collapse resulting from bacterial endotoxin. The present studies address the mechanism by which TNF causes hypotension and provide evidence for elevated production of nitric oxide, a potent vasodilator initially characterized as endothelium-derived relaxing factor. Nitric oxide is synthesized by several cell types, including endothelial cells and macrophages, from the guanidino nitrogen of L-arginine; the enzymatic pathway is competitively inhibited by NG-methyl-L-arginine. We found that hypotension induced in pentobarbital-anesthetized dogs by TNF (10 micrograms/kg, i.v., resulting in a fall in mean systemic arterial pressure from 124.7 +/- 7 to 62.0 +/- 22.9 mmHg; 1 mmHg = 133 Pa) was completely reversed within 2 min following administration of NG-methyl-L-arginine (4.4 mg/kg, i.v.). In contrast, NG-methyl-L-arginine failed to reverse the hypotensive response to an equivalent depressor dose of nitroglycerin, a compound that acts by forming nitric oxide by a nonenzymatic, arginine-independent mechanism. The effect of NG methyl-L-arginine on TNF-induced hypotension was antagonized, and the hypotension restored, by administration of excess L-arginine (100 mg/kg, i.v.). Our findings suggest that excessive nitric oxide production mediates the hypotensive effect of TNF. PMID- 2333309 TI - [Alternatives to animal testing]. PMID- 2333310 TI - Synthesis of 2,5-disubstituted benzimidazoles, 1,3,4-thiadiazoles and 3,5 diiodosalicylanilides as structural congeners of rafoxanide and closantel. AB - The synthesis of a series of 2,5-disubstituted benzimidazoles (8-10, 13), substituted 3,5-diodosalicylanilides (6, 7, 11, 12, 16-29), 2-(4-substituted phenyl)-4-aroylamino-1,3,4-thiadiazoles (33-38) and benzoxazines (14, 30, 31) has been carried out as the structural congeners of rafoxanide and closantel. All the compounds have been tested for their anthelmintic activity against Ancylostoma ceylanicum, Nippostrongylus brasiliensis, Hymenolepis nana and Cysticecus fasciolaris in rodents. Compounds 8, 22 and 23 exhibited 90-100% elimination of the hookworms A. ceylanicum and tapeworms H. nana from hamsters and rats, respectively, at an oral dose 50-250 mg/kg body mass. PMID- 2333311 TI - [Kinetics of the transformation of dihydroambazone into ambazone]. AB - The oxidation of dihydroambazone (1) by oxygen is dependent on the pH-values of the solutions used. This transformation can be inhibited and excluded, respectively, by ascorbic acid using defined concentrations. The oxidation product ambazone (2) was determined spectroscopically at different pH-values. The rate of transformation in serum depends on the temperature and can also be inhibited with ascorbic acid. PMID- 2333312 TI - Lithium acetate gastrointestinal diffusion system. Part 1: Lithium acetate single unit gastrointestinal diffusion system: preparation and release rate studies. AB - The gastrointestinal diffusion system (GDS), containing lithium acetate (1), releases the drug by a controlled source of diffusion energy. The unit can possibly be used for all soluble drugs in which solubility is independent from the pH of the gastrointestinal contents as is the case with 1. The one compartment unit is obtained by tabletting the drug and coating the tablets with a membrane of cellulose acetate to which soluble porofores-gum arabic, sodium chloride, 1-are added. When the pore-creating substance is dissolved out of the coating, there remains a porous film, which controls the rate of release of the drug. The release characteristics depend on membrane composition and mass. The systems reported here provided for zero-order drug delivery in vitro. PMID- 2333313 TI - [The content-uniformity of dispensary-prepared rectal suppositories]. AB - Rectal suppositories, which are dispensed according prescription in small numbers up to N = 30, do not satisfy the demands in respect of content uniformity, if we consider the last N/10 poured ones. This by sedimentation caused problem is to be solved in increasing the amount of substances by N/10, so that you will get a safety-amount of 15% totally. PMID- 2333314 TI - [Antimicrobial action of new imidazolinium compounds]. AB - Syntheses and antibacterial activity of 1-ethyl-2-alkyl-3-(alkoxymethyl)- and 1 ethyl-2-alkyl-3-(alkylthiomethyl)imidazolinium chlorides are described. Syntheses of the imidazolinium compounds were performed by reaction of 1-ethyl-2 alkylimidazoline with chloromethylalkyl ether or with chloromethylalkyl sulfide. Antimicrobial properties of obtained compounds was tested on 13 strains of bacteria and fungi. Chlorides with alkylthiomethyl residue showed the highest antimicrobial activity. PMID- 2333315 TI - [Antineoplastic activity and toxicity of dihydroambazone in comparison with ambazone (1,4-benzoquinone-guanylhydrazone-thiosemicarbazone)]. AB - Dihydroambazone 1, a soluble derivative of ambazone, was tested with an admixture of ascorbic acid (0.1, 0.25, or 0.5% in distilled water) for antineoplastic activity by different routes (i.p., p.o., s.c., i.v.) against leukemia P388, and by s.c. application against Lewis lung carcinoma on B6D2F1-mice. The results were compared with that of ambazone. 1 was as active as ambazone upon the per os d 1-4 schedule only. Ascorbic acid, added for stabilization of 1, had no significant influence on the results. Intravenously given 1 was of low activity. It proved to be toxic at 100 mg/kg body mass. The i.v. toxicity was estimated approximately on B6D2F1-mice (LD50: 150 mg/kg; LD100: 175 mg/kg; maximum tolerated dose (MTD): 100 mg/kg. A comparison between the MTD's of 1 and ambazone in mice and rats (Wistar) showed partly a somewhat better p.o. compatibility of 1. The expectation of a favourable i.v. applicable derivative from the otherwise in water nearly insoluble ambazone could not be realized. PMID- 2333316 TI - Treatment of dermatitis caused by the sesquiterpene lactone helenin. AB - Many sesquiterpene lactones, terpenoid compounds present in members of the Compositae (Asteraceae) family of plants, are known to cause allergic contact dermatitis. There is no treatment of this skin disease. We report on the use of an amino acid, L-cysteine, to control dermatitis in guinea pigs sensitized to the sesquiterpene lactone, helenin. The cysteine treatment of allergic reactions induced by helenin reduced the recovery time of the animals by about 50%. The effect of cysteine treatment might be explained by: cysteine reaction with free helenin, and substitution of skin proteins from the protein-helenin complex by cysteine through competitive reactions. Cysteine treatment present a new promising way for control of this type of allergy in humans. PMID- 2333317 TI - Anticholinergic properties of propiverine and its metabolites. PMID- 2333318 TI - Study of the essential oil of Lavandula dentata L. PMID- 2333319 TI - Pharmacology of cyclosporine (sandimmune). PMID- 2333320 TI - Comparative anti-ischemic effects of dihydropyridine calcium antagonists in isolated perfused rat hearts: relationship of cardiodepression and cardioprotection. AB - A comparison was made of the anti-ischemic effects of dihydropyridine calcium antagonists in isolated globally ischemic rat hearts. Pretreatment with amlodipine, nifedipine, nitredipine, or nisoldipine reduced reperfusion enzyme (lactate dehydrogenase) release and contracture after 25 min of global ischemia and 30 min of reperfusion. Increasing concentrations of all compounds resulted in proportionally smaller reductions in the severity of ischemia, with larger decreases in nonischemic tissue contractility occurring. Reperfusion function was significantly improved at 30 min with nifedipine only; however, at 60 min reperfusion function was significantly improved for all except nisoldipine. Washout data from nonischemic hearts (rate of disappearance of cardiodepressant effects) showed that the dihydropyridines washed out in the following order (fastest to slowest): nifedipine greater than nitrendipine greater than nisoldipine greater than amlodipine. Thus, these dihydropyridines are anti ischemic, though at higher concentrations cardiodepressant effects increase disproportionately. Differences in washout also effect the ability of these compounds to improve reperfusion function. PMID- 2333321 TI - Effects of delayed administration of methohexital and ketamine on posthypoxic cell damage of primary neuronal cultures. AB - Primary neuronal cultures from chick embryo cerebral hemispheres received NaCN (cytotoxic hypoxia) for 120 min and were then allowed to recover. Methohexital (300 mumol/l) or ketamine (30 mumol/l) given either before or during the hypoxic period elevated adenosine triphosphate (ATP) content of the cultures 15 min after hypoxia. Prehypoxic administration of ketamine also preserved the structural integrity and ATP content of neurons 20 h later, while methohexital did not. Ketamine elevated ATP content as measured 20 h after hypoxia even when administered 15 min after beginning of recovery. Pharmacokinetic reasons for contradictory effects of ketamine on neuronal cell loss in vivo ischemia studies and our in vitro experiments are discussed. PMID- 2333322 TI - Kinetic fate of potassium embelate, a non-narcotic centrally acting analgesic after oral and intravenous administration. AB - The pharmacokinetics of oral and intravenous potassium embelate (20 mg/kg) was studied in rats. The results revealed that this compound follows a biexponential kinetic pattern. Absorption was complete (bioavailability 97%) and fast. The disposition half-life is 9.5 h on intravenous and 11 h on oral administration. High concentrations of the drug were found in brain between 0.25 and 2 h, which is in agreement with its pharmacological action. The kidney plays a major role in the excretion of the drug. PMID- 2333323 TI - On the biophysical interpretation of the mathematical product of dose and relative biological effectiveness. AB - The mathematical product of dose and relative biological effectiveness (DR) is commonly used empirically as the 'effective' dose of radiations. It is often interpreted as the equivalent dose of a reference radiation, such that the individual DRs of the radiation components are summed like physical doses in a mixture of radiations with different RBE values. It is shown that such a physical interpretation of DR would be both mathematically and logically inconsistent unless the action of each radiation has a constant RBE value for all end-effects. This is contrary to general experimental findings. Based on the isoeffect biological connotation in the definition of RBE, a biophysical interpretation is being introduced in this paper in which DR is always interpreted with respect to a particular end-effect on which the RBE value is evaluated, somewhat similar to having an extra biological dimension. Hence, only DRs evaluated for the same end effect can be meaningfully computed together in a mixture. From the empirical results of radiobiological experiments using mixtures of radiations of different qualities, DRs of radiation components are shown to be additive in a mixture just like physical doses. A convenient linear computation framework is, therefore, available for the use of DRs in the empirical calculation of effect of mixtures of radiations of different qualities. The bearing of this biophysical interpretation of DR on radiation protection and treatment planning is discussed. PMID- 2333324 TI - Improved clinical facility for in vivo nitrogen measurement. AB - The design and construction of a hospital clinical facility for in vivo prompt gamma neutron activation analysis for total body nitrogen (TBN) measurement is described. The use of 252Cf neutron sources gives a better signal-to-background ratio compared with 238Pu-Be sources of equal strength, thus yielding better reproducibility of measurements. By measuring the hydrogen and nitrogen signals separately using appropriate gating circuits, signal-to-background ratio is further improved. Measurements using a urea phantom (5.63 kg nitrogen as urea in 34.53 kg of water) show that 2 x 6 micrograms 252Cf sources gives a nitrogen signal-to-background ratio of 5.6 (compared with 3.4 in the case of a 2 x 10 Ci 238Pu-Be source) and a reproducibility for nitrogen signal of +/- 1.1% (CV) and for hydrogen signal (internal standard) of +/- 2.33% (CV). Approximately 30 minutes of patient's time is required for each TBN measurement with an estimated reproducibility of +/- 3.8% (CV). The radiation dose to the patient is about 0.2 mSv (effective dose equivalent; QF = 10) per 20 min measurement. A report for the clinician is produced within a few minutes after the measurement by a dedicated IBM-PC computer. The entire facility is clean, comfortable and the electronics and computer processing are simple and economical. PMID- 2333325 TI - Probability modelling of a surgical probe for tumour detection. AB - Probability functions for the output counts from a radiation detector probe are needed to implement Bayesian detection strategies or to assess performance of the probe. This paper presents methods for simulating a surgical probe designed for tumour detection to obtain statistical information for modelling probability functions of output data. Statistical models of pharmaceutical uptake in normal organs and tumours were estimated from animal and human data, and these models were combined with a digitised human torso phantom to create a large set of simulated patients. With the simulated patients and with a spatial map of the probe response, computer simulations of intraoperative probe measurements provided a large set of simulated probe data. Probability models derived from these data using maximum-likelihood methods helped to formulate the detection strategy and to evaluate the performance of the surgical probe. PMID- 2333326 TI - Consequences of combining strength and endurance training regimens. AB - A common belief among many clinicians and trainers is that intensive simultaneous training for muscle strength and cardiovascular endurance is counterproductive. To test this premise, 14 healthy, untrained men trained four days per week for 20 weeks on a bicycle ergometer for endurance (END Group, n = 4), on an isokinetic device for increased torque production (ITP Group, n = 5), or on both devices (COMBO Group, n = 5). The ITP and COMBO groups had equal torque gains throughout the study (234 +/- 45 and 232 +/- 23 N.m, respectively). After 11 weeks, both END and COMBO groups had similar gains in maximal oxygen consumption (VO2max) (in milliliters per kilogram of body weight per minute). During the last half of the study, however, the END Group had a significant gain in VO2max (p less than .05) of 4.7 +/- 1.2 mL.kg-1.min-1, whereas the COMBO Group had a nonsignificant gain (p greater than .05) of 1.8 +/- 0.6 mL.kg-1.min-1. In harmony with this finding, the END Group showed a significant increase (p less than .05) in citrate synthase activity (15.5 +/- 7.9 mumol.g-1.min-1), whereas the COMBO Group had no significant increase. The authors concluded that simultaneous training may inhibit the normal adaptation to either training program when performed alone. The extent of the interference probably depends on the nature and intensity of the individual training program. [Nelson AG, Arnall DA, Loy SF, et al: Consequences of combining strength and endurance training regimens. PMID- 2333327 TI - Energy cost of walking with hip joint impairment. AB - The energy cost of walking was measured in 12 patients (age 39-73 years) with hip joint impairment and 10 healthy controls during unassisted walking (2-6 km.h-1) on a level treadmill surface and on a 5% incline. The energy cost of locomotion in most patients increased up to 50% and 70% during level-surface and uphill walking, respectively. This difference between patients and controls was probably due to the increased external mechanical work. The energy cost of walking, although related to pain experienced during walking but not to hip joint range of motion or to joint status evaluated radiographically, provides an additional variable when defining the conditions of disability and functional impairment in individuals with this pathological condition. [Gussoni M, Margonato V, Ventura R, et al: Energy cost of walking with hip joint impairment. PMID- 2333328 TI - Relationship of extremity muscle torque and bone mineral density in postmenopausal women. AB - The purpose of this study was to examine the correlations between the torque of four extremity muscle groups and the bone mineral density (BMD) of the lumbar spine and hip in postmenopausal women. Fifty-six postmenopausal women (means age = 55.4 years, s = 7.1; means height = 162.6 cm, s = 6.4; means weight = 65.9 kg, s = 9.3) served as subjects. Bone mineral density was measured from the L2-L4 vertebral bodies, greater trochanter, femoral neck, and Ward's triangle using dual-photon absorptiometry. Hip abduction, knee extension, hip flexion, and grip force were assessed using the Spark Muscle Examination and Exercise Dosimeter (MEED) 3000 system. The Pearson product-moment correlations between muscle torque and BMD ranged from .07 to .42. The significant (p less than .05) correlations between torque and BMD (r = .27-.42) occurred in functionally and anatomically related areas. Results of this study demonstrate a statistically significant relationship between torque and BMD in anatomically related areas in postmenopausal women. This relationship, however, is not sufficiently strong to allow for prediction of BMD from the four muscle groups tested in this study. The relationship does suggest that strength may be a factor in the determination of BMD. Maintenance of strength in those muscle groups with anatomical or functional relationships to the hip and lumbar spine may play a role in the prevention and cessation of the osteoporotic changes that occur. PMID- 2333329 TI - A profile of faculty development in physical therapy education programs. AB - The purpose of this study was to report on the status of faculty development in physical therapy education programs. A survey questionnaire was sent to the directors of 110 physical therapy programs nationwide. Analysis of responses from respondents (n = 79; 72%) demonstrated 1) criteria used to evaluate faculty members were similar among different institutions, 2) fewer than half of the institutions have a faculty development plan (FDP), 3) the majority of those institutions that have an FDP supported similar areas and activities to facilitate faculty development, and 4) respondents used creative ways to support faculty development. The results appear to indicate that most physical therapy programs do not have a formalized program to assist faculty members in their development of skills in research, teaching, and service. [Rothman J. Rinehart ME: A profile of faculty development in therapy education programs. PMID- 2333330 TI - The novice versus the experienced clinician: insights into the work of the physical therapist. AB - The purpose of this study was to develop a conceptual framework and a data collection tool to begin a systematic analysis of the work of the physical therapist. The primary method of data collection was nonparticipant observation of physical therapist-patient treatment sessions. A team of two researchers performed each of the observations. Eight physical therapists, representing three levels of experience, were observed in four different adult outpatient orthopedic settings. Field notes constructed from the observations and transcribed data were used to develop coding categories. These categories were the basis for the development of five themes that describe some aspects of the therapeutic intervention: 1) how treatment time is allocated, 2) the types and uses of information gathered from the patient, 3) the impact of the therapeutic environment, 4) the degree of responsive therapeutic interaction, and 5) the therapist integration of nontherapeutic interaction with therapeutic interaction. These findings are a beginning for understanding the practice of physical therapy. PMID- 2333331 TI - Conservative care. PMID- 2333332 TI - Photochemical and photophysical properties of piroxicam and benoxaprofen in various solvents. AB - Laser flash spectroscopy was used to examine the title compounds. Piroxicam has a triplet transient with a maximum near 450 and a lifetime of 3-21 microseconds depending on the solvent. The relative quantum yield is highly solvent dependent being maximum in toluene and greater than or equal to 14 fold lower in hydrogen bonding solvents. There is another transient which is assigned as a proton transferred ground state transient. Some permanent photoproduct also appears to be produced. Benoxaprofen also has a triplet transient with a maximum near 420 nm with a lifetime of 65 microseconds to greater than or equal to 250 microseconds depending on the solvent. In this case, the relative quantum yield only slightly varies among polar and hydrogen bonding solvents. This is in marked contrast to published data on the fluorescence yield. Some permanent photoproduct appears to be produced. PMID- 2333333 TI - The photochemistry of acetyl-substituted aroyl azides: the design of photolabeling agents for inert sites in hydrophobic regions. AB - The photochemistry, photophysics and hydrolytic stability of three substituted aroyl azides were investigated. The azides were selected as model compounds for potential photolabeling agents based on the extreme electrophilic reactivity of aroylnitrenes. Each of the azides studied is a derivative of benzoyl azide containing an acyl group to act as an internal triplet sensitizer and an additional functional group useful for linking the azide to a site-selecting probe molecule. The findings show that benzoyl azides containing the three substituents in a 1,3,5-pattern might be useful for labeling of lipophilic molecules. PMID- 2333334 TI - Quantitative conversion of the (6-4) photoproduct of TpdC to its Dewar valence isomer upon exposure to simulated sunlight. AB - It has been found that the (6-4) photoproduct of thymidylyl-(3'----5') deoxycytidine (TpdC) is converted quantitatively to a further photoproduct upon exposure to Pyrex-filtered medium pressure mercury arc light. Infrared UV, FAB MS, 1H NMR, 13C NMR and 31P NMR spectra were obtained for both the (6-4) product and its photolysis product. 1H NMR assignments were made on the basis of proton decoupling and homonuclear shift correlated experiments and 13C NMR assignments were made on the basis of proton-detected heteronuclear shift correlated experiments. The Dewar pyrimidinone structure was assigned to the photolysis product by analysis of the spectral data in comparison to those of the Dewar photoproduct of TpT and other Dewar pyrimidinones. The (6-4) product of TpdC is the second member of the class of (6-4) photoproducts that has been found to photoisomerize to its Dewar valence isomer upon exposure to wavelengths greater than 280 nm, the first being that of TpT (Taylor and Cohrs, 1987, J. Am. Chem. Soc. 109, 2834-2835). These results further support the proposal that all members of the (6-4) photoproduct class are converted to their Dewar valence isomers upon exposure to sunlight. PMID- 2333335 TI - Dithionite treatment of flavins: spectral evidence for covalent adduct formation and effect on in vitro bacterial bioluminescence. AB - Intrigued by the apparent requirement of dithionite for FMN reduction (as opposed to photoreduction or catalytic hydrogenation) in the H2O2-initiated bacterial bioluminescence reaction, we chose 5-ethyl-3-methyllumiflavinium cation I as a model to investigate possible flavin adduct formation by treatment with dithionite or (bi)sulfite. In the range of pH 5-8, the reaction of dithionite with 5-ethyl-3-methyllumiflavinium cation, which is in equilibrium with the 5 ethyl-4a-hydroxy-3-methyl-4a, 5-dihydrolumiflavin pseudobase II (X = OH), is not limited to the formation of flavosemiquinone and dihydroflavin following two one electron steps. Several parallel and sequential reactions may take place involving the intermediacy of covalent flavin adducts. Addition of (bi)sulfite gave a 4a-sulfiteflavin adduct II (X = SO3-). Consistent with the S2O4(2-) in equilibrium with 2 SO2-. equilibrium, the reaction of dithionite and II (X = OH; SO3-) gave rise to two flavin adducts in competitive nucleophilic displacements: a 4a-sulfoxylate-flavin radical (II, X = SO2.) and a 4a-dithioniteflavin adduct (II, X = S2O4-), respectively. On increasing the (S2O4(2-), SO2.-)/flavin ratio under N2, the formation of the 4a-sulfoxylate-flavin radical became predominant. The II (X = SO2.) so formed was in equilibrium with the flavosemiquinone and bisulfate and can be trapped by reacting with hydroxylamine. In the initial presence of oxygen, II (X = SO2.) was highly reactive toward O2, giving a fast oxidation to II (X = SO3-) and effectively suppressing the formation of the flavosemiquinone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333336 TI - Hypothalamic sites of progestin action on aggression and sexual behavior in female Syrian hamsters. AB - The effects of intracranial implants of the synthetic progestin, promegestone (R5020), on aggression and sexual behavior were examined in female Syrian hamsters. Ovariectomized female hamsters showed high levels of aggression and no lordosis towards stimulus male and female hamsters, both prior to and after estradiol benzoate treatment. Forty-six hr after estradiol treatment (10 micrograms SC), 10% crystalline promegestone was applied bilaterally (27 ga cannulae) to the ventromedial hypothalamus. When tested 5-7 hr later, these animals had a significant reduction in the rate of attacks towards females, with no lordosis responding to a male. In contrast, promegestone in the caudal anterior hypothalamus activated low levels of lordosis, yet these females maintained high levels of aggression towards stimulus females. Females receiving promegestone in the rostral anterior hypothalamus, and control females receiving intracranial cholesterol, maintained high levels of aggression and no lordosis. Estradiol treatment alone enhanced pelvic movements in response to experimenter applied perineal stimulation in a majority of females (18/22 compared with 4/22 prior to estradiol injection), with intracranial treatments having no further effect. These results indicate that progestins act on aggression and sexual behavior in female Syrian hamsters at different hypothalamic loci. PMID- 2333337 TI - Efficiency and persistence of licking in rats. AB - Thirsty rats tested in 60-min sessions licked an empty spout for access to a water spout. We raised the behavioral price of the water lick by requiring more licks at the empty spout per lick at the water spout. At relatively high prices the rats made relatively few water licks but licked more efficiently, getting more water per lick. Controls showed that the rise in efficiency with price was not attributable to two variables previously confounded with price: the total number of water licks, and the temporal pattern of access. At a higher price the rats also licked more persistently, making more extra water licks before the shutter could occlude the spout. However, yoked controls showed that the greater persistence resulted not from price, but from the relatively stringent pattern of access that accompanied the higher price. Extra water licks diminished as the session progressed, apparently from satiety, not fatigue. The results have implications for behavioral ecology, behavioral economics, motivation, and the methodology of reward. PMID- 2333338 TI - Hippocampal lesions are without effect on olfactory memory formation in the context of pregnancy block. AB - Female mice which have mated and are subsequently exposed to male urine odours (pheromones), which differ from those of the male that mated (stud male), undergo hormonal changes resulting in a block to pregnancy. Since the stud male's odour blocks the pregnancy of females other than those he mated, this would suggest that a memory specific for this male's odour is established at the time of mating. Hippocampal lesions, when made prior to mating, did not disrupt memory formation to the odour of the stud male. This male's odour did not block pregnancy, while changing odour to that of the strange male did block pregnancy. In order to establish the functional effectiveness of these hippocampal lesions, olfactory discriminations were examined in a modified T-maze. The odour discrimination was urine-soiled bedding taken from a cage of different strain males versus same strain bedding. After 35 trials, neither control nor lesioned females were performing above chance level (50% correct responses), indicating the difficulty in cognitively learning this discrimination. These female mice were therefore trained to distinguish a novel odour (butyl acetate) from familiar strain urine-soiled bedding. Hippocampal-lesioned females were slower to acquire this discrimination and did not perform above chance level after 35 trials, in contrast to the 70% success of sham-lesioned females. Hence, hippocampal lesions, while producing a deficit in olfactory learning in the maze test, are without effect on the formation or retrieval of the specific olfactory memory formed for the stud male at mating, as revealed from pregnancy block tests. PMID- 2333339 TI - Conditioned taste avoidance induced by lactose ingestion in adult rats. AB - Because adult rats have very low levels of the intestinal enzyme lactase, the ingestion of appreciable quantities of the disaccharide lactose may cause gastrointestinal distress. The present experiment was designed to demonstrate that adult rats will learn to avoid previously neutral stimuli which have been paired with lactose ingestion. Adult rats ingested both a novel solution [either tap water (WA) or 0.1% saccharin (SA)] and a novel food substance (49% powdered lab chow + 50% added disaccharide + 1% saccharin) during a single conditioning session. The added disaccharide was either sucrose (group SU-SA), lactose (groups HL-SA and HL-WA), or equal amounts of these two disaccharides (group LL-SA); a fifth group (LC-SA) consumed a sucrose-containing diet to which lithium chloride was added (5 mg per 1 g of diet). Separate feeding tests and drinking tests, carried out over several weeks, were used to assess the extent of conditioned taste avoidance. In the four feeding tests, rats were allowed to ingest powdered lab chow with added saccharin (but without added disaccharide), while in the four drinking tests, rats chose between tap water and a 0.1% saccharin solution. Group HL-SA demonstrated a substantial conditioned avoidance in both feeding and drinking tests, but group HL-WA showed avoidance only in feeding tests. Conditioned avoidance was weak in group LL-SA; the strongest avoidance was observed in lithium chloride-treated rats (group LC-SA). Results are related to previous research and to the hypothesis that a learned avoidance of milk may facilitate the weaning process in mammals. PMID- 2333340 TI - The effects on schedule-induced attack of covarying meal size and spacing. AB - Pigeons were exposed to fixed-time food schedules of 30, 120, and 480 sec with two reinforcer magnitudes at each. Attack behavior against a rear-projected conspecific image was assessed at each interfood/reinforcer magnitude combination. For seven of eight subjects, attack rate was related to interfood interval by an inverted-U or bitonic function. The larger reinforcer magnitude typically induced more attack than the smaller. PMID- 2333341 TI - Baseline and reactivity measures of blood pressure and negative affect in borderline hypertension. AB - Measures of blood pressure (BP) and negative affect were taken prior to, immediately following, and ten minutes after a cognitive stressor in groups of normotensive (group N; n = 15) and borderline hypertensive (group B; n = 15) young adults. Two testing sessions, one week apart, involved performance of a simple, congruent color-word ("easy") and a cognitive stress-inducing, incongruent color-word ("difficult") version of the Stroop test. In both sessions, group B showed significantly higher baseline systolic and diastolic BP, higher systolic responses to the difficult Stroop task, and higher recovery measures of systolic and diastolic BP than group N. In general, group B had significantly elevated baseline and reactivity scores on state measures of negative affect in both sessions. Correlations revealed strong positive associations between blood pressure and mood reactivity only for borderline subjects. Depressed mood was more strongly and consistently related to blood pressure reactivity than was hostility. Borderline hypertension appears to be associated with stable, perhaps clinically significant elevations in negative affect, and with dysphoric response to mild cognitive stress. PMID- 2333342 TI - Age-related alterations in cardiac response to emotional stress: relations to behavioral reactivity in the rat. AB - Age and behavioral characteristics are considered as risk factors for disturbances of the cardiac rhythm. Emotional stress may be a disseminating factor. Therefore, cardiac responsiveness and behavioral reactivity and their relation as a function of age have been studied in the rat. Young (3-month-old) and young adult (5-month-old) rats display a relative deceleratory cardiac response with bradyarrhythmias in the initial phase of response to emotional stress evoked by stimuli associated with a previous painful experience. The behavioral response is immobility. The immobility response is also displayed by aged (21-month-old) and senescent (33-month-old) rats but the initial bradycardiac heart response to emotional stress is absent, and the incidence of repetitive extrasystoles is increasing with age. An inverse correlation between behavioral reactivity to novel stimuli and the bradycardiac heart responsiveness is observed in young and young adult individual animals. The behavioral reactivity of the aged and senescent rats is diminished, but the correlation with cardiac reactivity remains preserved. It is suggested that the behaviorally coupled inhibitory influences on the heart are diminishing during aging either due to impairments in the descending cholinergic (vagal) system or secondarily, due to a decrease in the central "drive" of this system. PMID- 2333343 TI - Haloperidol does not antagonize the effects of stress on aggressive behaviour in mice. AB - The possibility that antipsychotic drugs antagonize the behavioural effects of stress on agonistic behaviour has been explored. Male mice of the OF.1 strain were subjected to the following treatments: 1) Immobilization stress (ten or twenty minutes in duration), 2) haloperidol (three doses) and 3) immobilization stress (ten minutes) plus haloperidol. Individually housed experimental animals confronted standard opponents (anosmic animals) in ten-minute encounters in a neutral cage. Encounters were videotaped and behaviour evaluated, assigning times allocated by subjects to eleven broad behavioural categories. The data show that stress markedly decreases attack behaviour, but haloperidol does not protect against the disruptive action of immobilization. On the contrary, stress and haloperidol produced additive effects further decreasing attack and increasing immobility. PMID- 2333344 TI - Variations in food preference and consumption across the menstrual cycle. AB - There is some evidence that food consumption changes across the menstrual cycle. However, archived studies tend to rely on self-report data and do not differentiate among types of food eaten. The present laboratory study was designed to measure women's taste preferences and specific food consumption across the menstrual cycle. Women came into the laboratory, consumed everyday foods, and rated them on taste judgment scales. The foods were weighed before and after the tasting session to determine amount eaten. After the tasting session, subjects completed several questionnaires (e.g., measures of affect, restrained eating, menstrual cycle and menstrual symptoms). Physical measurements (e.g., height, weight) were taken at the end of the session. Sweet food consumption and preference ratings were significantly higher during the premenstrual period. Consumption and ratings of other foods did not differ. There were no differences in levels of mood, obesity, or restrained eating across the menstrual cycle. Low restraint was associated with reporting fewer menstrual symptoms, in general, and slightly better mood. These results support the idea that specific taste preferences change over the menstrual cycle, and that endocrinological factors could be involved in this phenomenon. PMID- 2333345 TI - Pinealectomy prevents short photoperiod inhibition of male hamster sexual behavior. AB - The role of the pineal gland in mediating photoperiodic influences on copulatory behavior (CB) of male hamsters (Mesocricetus auratus) was assessed in the presence and absence of testosterone (T). The results demonstrate that the pineal gland is necessary for short photoperiod exposure to alter CB. Sexually experienced males were exposed to either long (14L:10D; LP) or short (8L:16D; SP) photoperiods for 13 weeks; after the first 2 weeks of exposure, all animals were castrated and then either pinealectomized (PINX) or sham operated (SHAM PINX). CB tests over an 8-week period following surgery indicated that copulatory impairments developed in all animals, but deficits occurred more rapidly among short photoperiod males with intact pineal glands (SP-SHAM PINX), compared to pinealectomized males housed in either the long (LP-PINX) or short photoperiod (SP-PINX). LP-PINX and SP-PINX animals were not statistically different on any of the CB measures examined. Nine weeks after castration (11 weeks of photoperiod exposure), all hamsters were given a T-filled Silastic capsule to restore CB. Restoration of sexual behavior was less rapid and less complete among SP-SHAM PINX hamsters. Additionally, males in this group took longer to initiate copulation relative to the pinealectomized hamsters. These findings are compared to other reports suggesting that photoperiodic effects on the sexual behavior of female hamsters do not require an intact pineal gland. PMID- 2333346 TI - Fetal uterine position affects copulation and scent marking by adult male gerbils. AB - Those male Mongolian gerbils (Meriones unguiculatus) that as fetuses resided in uterine locations adjacent to no females, when adult, scent marked more frequently, mounted estrous females with shorter latencies, and ejaculated after fewer intromissions than did those male gerbils that as fetuses resided in uterine locations adjacent to two females. Both the scent-marking frequencies and copulatory patterns of adult males were positively correlated with three indices of their circulating levels of testosterone: ventral gland size, anogenital distance, and relative testes weights. Also, those males that scent marked relatively frequently copulated more reliably than did those males that scent marked relatively infrequently. PMID- 2333347 TI - Estrous cycle irregularities in overfed rats. AB - Hypothalamic and genetic obesities in rodents are usually associated with reproductive impairments, but the underlying etiology of the latter is not clear because of concomitant metabolic abnormalities in these animal models. In the present study metabolically intact rats were used and obesity was developed by offering the rats a cafeteria-type diet. Purina chow-fed animals were used as control. Cafeteria feeding was associated with hyperphagia and an increased brown adipose tissue (BAT) thermogenesis, in association with long estrous cycles (p less than 0.01). The latter was accounted for by a long diestrous phase (p less than 0.02). Replacement of the cafeteria diet with purina rat chow corrected the estrous cycle irregularities, as caloric consumption and body weight were reduced. We propose, as a working hypothesis, that reproductive functions are finely tuned with body temperature, and that an excess feeding-induced BAT thermogenesis may underlie the disruption in estrous cycle observed during overfeeding. PMID- 2333348 TI - Genotype-environment interaction and the correlation structure of behavioral elements in paradise fish (Macropodus opercularis). AB - Three inbred strains and all their possible F1 crosses were monitored in one familiar and three unfamiliar situations. Their behavior was described by species specific elements of the ethogram. Genetic variability was demonstrated both for behavioral elements and for factors extracted by Principal Components Analyses (PCA). We studied how the behavior of genetically different fish changed across situations and examined the interrelations both among variables measured in one situation and between those measured in different ones. Behavioral changes across situations proved to be different for certain strains and crosses, that is, genotype-environment interaction was found. The PCA's carried out for the 4 situations separately yielded unlike factor structures. Another PCA, in which all the variables were included, proved that there was correlation among certain variables measured in different situations. In general, it seems that the corresponding behavioral elements do not always represent the same phene in different situations. We discuss how the genotype-environment interactions can be interpreted, try to define behavioral strategies using the extracted factor structures, and construct a model for the organization of Macropodus behavior. PMID- 2333349 TI - Effects of cold acclimation on the energetic metabolism of the staggerer mutant mouse. AB - Staggerer mutant mice are lean despite their hyperphagia. Brown adipose tissue activity may be implicated in this phenomenon. The aim of this work is to determine the energetic metabolism and to detail some characteristics of the brown adipose tissue of Staggerer mutant mice born and reared either at 28 degrees C (within the thermoneutral zone) or 22 degrees C (cold temperature) compared to nonmutant control mice. In mutant mice reared at thermoneutrality the resting metabolism was found to be higher than that of controls, and further the activity of the brown adipose tissue increased as indicated in relative mass, composition and cytochrome oxydase activity. A stimulatory effect of cold exposure was observed in both mutant and nonmutant mice. It is suggested that Staggerer mice may provide a good model for the study of the cold-induced or diet induced mechanisms of brown fat stimulation. PMID- 2333350 TI - An adaptable microcomputer program for recording behavior durations. AB - A versatile and easy to use program is described for monitoring and recording behavior durations on IBM-compatible microcomputers. The program also records frequencies and provides latency information. Among its more prominent attributes are its ability to accommodate a broad range of behavioral assays and the facility with which its operation can be mastered. It requires no specialized hardware and is capable of being used in conjunction with a number of commercially available software packages for statistical analysis. PMID- 2333351 TI - Dose and temporal parameters of morphine-induced hyperalgesia in domestic fowl. AB - Recent research in this laboratory has identified a biological model in which morphine produced a hyperalgesic response to a noxious thermal stimulus. Morphine effects, however, were examined at only one injection-to-test interval (10 min). Because a single injection-to-test interval is relatively uninformative, the present research was designed to more fully characterize this morphine hyperalgesic effect. In Experiment 1, 15-day-old White Leghorn cockerels were placed on a hot plate (59 degrees C) in 10 min after injection of morphine (1.25, 2.5, 5.0, 10.0 mg/ml/kg) or the distilled water vehicle (1 ml/kg). Latency to perform a jump response or attainment of a 90-sec no-jump criterion were recorded. Experiment 2 examined morphine effects (2.5 mg/ml/kg) on hot plate jump latencies at various injection-to-test intervals (10, 30, 60, and 240 min). Morphine produced a dose-dependent hyperalgesic response. Temporal characteristics of morphine effects were evident as a U-shaped function. The dose and temporal characteristics of morphine-induced hyperalgesia in White Leghorn cockerels are similar to the dose and temporal characteristics of morphine induced analgesia typically seen in other species. PMID- 2333352 TI - Sex differences in the flesh-eating preferences of wild house mice. AB - Freshly asphyxiated male or female house mice and prairie deer mice were presented to hungry male or female wild-strain house mice. Male subjects ate significantly more conspecific than contraspecific flesh, but females showed no statistically reliable preference. This sex difference, which is essentially opposite that previously reported in deer mice, is related to species-specific sex differences in aggressiveness using a response-competition model. PMID- 2333353 TI - Intensity and precision of circadian wheel running in three outbred rat strains. AB - The laboratory rat is widely used in many areas of neurobiologic and behavioral research. However, studies of circadian activity rhythms have usually employed other rodent species whose activity patterns are more amenable to measurement in the circadian paradigm. Nevertheless, the rat may be the optimal choice in certain investigations of circadian function because of the wealth of data on the neuroanatomy and neuropharmacology of this species. This study was undertaken to determine whether choice of rat strain could affect the quality of measured circadian activity data. Intensity of wheel running (wheel revolutions per day), precision of onset, and longevity of consistently interpretable running records were assessed in three common outbred rat stains, Long-Evans, Wistar, and Sprague Dawley. Long-Evans rats showed greater intensity of wheel running while entrained and at four and eight weeks of free running in constant darkness. There was no difference in precision of running onset among the three strains. Thus, use of the Long-Evans strain, with its greater intensity of wheel running and similar precision of activity onset, may confer advantages in studies involving measurement of circadian activity rhythms in the rat. PMID- 2333354 TI - HLA antigens in schizophrenia. AB - Human leukocyte antigen (HLA) typing was performed on 55 white schizophrenic patients, who were subdivided into groups on the basis of clinical subtype, response to neuroleptic treatment, enlargement of the lateral ventricles, presence of increased prefrontal or parieto-occipital markings, and presence of reversed frontal or occipital lobe asymmetry. No observed differences in antigen frequencies between the group as a whole and controls or between any subgroup and the remaining group or controls remained significant after correction for the number of antigens tested. PMID- 2333355 TI - Effect of anticholinergic medication on positive and negative symptoms in medication-free schizophrenic patients. AB - It is generally assumed that anticholinergic drugs have no effects on schizophrenic symptomatology. A few studies, however, indicate that anticholinergic agents aggravate psychotic symptoms and antagonize therapeutic effects of neuroleptics in schizophrenic patients; more recently, some investigators have observed that these agents appear to benefit negative symptoms. In an effort to resolve this issue, we studied the effects of 2 days of treatment with biperiden on positive and negative symptoms in 15 medication-free schizophrenic patients. Positive symptoms increased significantly, while there was a trend toward a decrease in negative symptoms. The implications of these findings for the role of the cholinergic system in schizophrenia are discussed. PMID- 2333356 TI - Distinguishing depression and negative symptoms in unmedicated patients with schizophrenia. AB - Depression can occur in schizophrenia but can be difficult to distinguish from negative symptoms of the illness. To evaluate whether concurrent use of the Hamilton Rating Scale for Depression (HRSD) and the Brief Psychiatric Rating Scale (BPRS) could successfully separate depression and negative symptoms, we examined ratings on 69 unmedicated schizophrenic inpatients. A classical BPRS depression subscale score correlated highly (rho = 0.80) with the HRSD total score. The classical BPRS "negative symptom" subscale score was unrelated to both the BPRS and HRSD depression summary measures. Among individual HRSD items, negative symptoms correlated only with work/activities and retardation. The findings suggest that negative and depressive symptoms may be assessed independently. PMID- 2333357 TI - Differential autonomic nervous system activity in multiple personality disorder. AB - The cardinal feature of multiple personality disorder (MPD) is the existence of two or more alter personality states that exchange control over the behaviour of an individual. Numerous clinical reports suggest that these alter personality states exhibit distinct physiological differences. We investigated differential autonomic nervous system (ANS) activity across nine subjects with MPD and five controls, who produced "alter" personality states by simulation and by hypnosis or deep relaxation. Eight of the nine MPD subjects consistently manifested physiologically distinct alter personality states. Three of the five controls were also produced physiologically distinct states, but these differed from those of the MPD subjects. A habituation paradigm demonstrated carryover effects at the ANS levels from one state to the next for both groups. PMID- 2333359 TI - Urinary amines in Tourette's syndrome patients with and without phenylethylamine abnormality. AB - Previous data indicated a subgroup of Tourette's syndrome patients with a beta phenylethylamine (PEA) level that was lower than all subjects in a control group matched for age and education. The current study compared the subgroups of Tourette's syndrome patients (n = 28) from the previous study with 20 control subjects in regard to other amines and metabolites. Patients with low levels of PEA were also found to have lower levels of 3-methoxy-4-hydroxy-phenylglycol, normetanephrine, serotonin, m-tyramine, and p-tyramine. There was also some evidence of dopaminergic abnormalities in the low-PEA subgroup. These data provide suggest a role of PEA in the pathophysiology of some patients with Tourette's syndrome. This effect may be mediated through other neurotransmitter systems. PMID- 2333358 TI - CSF diazepam-binding inhibitor in alcoholics and normal controls. AB - Diazepam-binding-inhibitor (DBI) and gamma-aminobutyric acid (GABA) are colocalized in neurons in the brain. This system has been implicated in anxiety and in the regulation of corticotropin-releasing hormone (CRH) secretion. Alcohol has direct and indirect effects on the functioning of GABAA receptors. Abstinent alcoholics are, on the average, more anxious than controls. In tests of animal behavior, DBI has anxiogenic, and alcohol has anxiolytic potency. Therefore, we compared alcoholic patients and healthy controls for cerebrospinal fluid (CSF) levels of DBI, and looked for a correlation between CSF levels of DBI and CRH. There was no significant difference in CSF concentrations of DBI between the two groups and no significant correlation between CSF DBI and our measure of anxiety. However, there was a significant positive correlation between CSF levels of DBI and CRH in both the alcoholic and control groups. PMID- 2333360 TI - Sensory physiology and catecholamines in schizophrenia and mania. AB - Hypersensitivity to sensory stimulation is a prominent characteristic of both schizophrenia and mania. Neurophysiological recordings suggest a common deficit in a central neuronal sensory gating mechanism which regulates sensitivity to repeated auditory stimuli. Dopamine and norepinephrine are hypothesized to have major roles in these illnesses, but their role in aberrant sensory processing has not yet been proved. Presumptive evidence for effects of catecholamines on sensory processing comes from psychophysiological studies of normal subjects challenged with stimulants who show decreased sensory gating, and studies of psychotic patients treated with neuroleptics who show improved function. Studies of similar phenomena in animals show comparable effects of catecholamines on sensory processing, both behaviorally and at the single neuron level. In this study, gating of auditory evoked potentials (EPs) during treatment of both illnesses was compared with plasma dopamine and norepinephrine metabolites. Comparisons of medicated and unmedicated states showed that schizophrenic patients have a fixed deficit in sensory gating, which is a familial trait, unchanged by medication. During acute illness, they have an additional transient hypersensitivity to stimuli, manifested as smaller EPs, which seems to be mediated by dopamine. Manic patients have only the deficit in sensory gating, which is transient and seems to be mediated by norepinephrine. Thus, similar neurophysiological deficits in the two psychoses are associated with different biochemical abnormalities, which may explain similarities in acute symptoms and differences in other aspects of the illnesses, such as their response to treatment. PMID- 2333361 TI - Dose-response profiles of plasma growth hormone and vasopressin after clonidine challenge in man. AB - The objective of the study was to determine dose-response relationships of growth hormone, vasopressin, blood pressure, heart rate, and behavioral responses to clonidine. Ten healthy male volunteers were tested with each of three doses of clonidine (0.7, 1.4, and 2.1 micrograms/kg) with at least 1 week between tests. All doses gave a significant growth hormone response with a peak at 50 min. The high dose gave a significantly higher response than either the medium dose or the low dose, which did not differ from each other. Within individual subjects, there was a consistency of response to the different doses; thus, three of the volunteers had responses of 5 ng/ml or higher to the low dose. Those three subjects had higher growth hormone peaks after the highest dose than did six other subjects. Vasopressin showed a drop following clonidine after the two higher doses. Systolic blood pressure dropped following clonidine, showing a significantly greater drop for the medium and high doses than for the low dose. Diastolic blood pressure also showed a drop, but responsiveness did not differ between doses. There was significant dryness of mouth produced by clonidine, but no difference between doses. There was a significant sedative effect following clonidine which was greater for the high dose than for the medium or low dose. The finding that some subjects had a growth hormone peak of 5 ng/ml or greater after the low dose supports the hypothesis that use of a low dose strategy may be useful in confirming supersensitivity in conditions where increased responsiveness is suspected. The lack of difference between blood pressure responses to the medium and high doses of clonidine--doses that have different effects on growth hormone--supports the hypothesis that differences in responsiveness of presynaptic and postsynaptic alpha 2-adrenergic receptors exist. PMID- 2333362 TI - [Evolution and development of the central nervous system]. PMID- 2333363 TI - [Formation of the neuron-circuit]. PMID- 2333365 TI - [Formation and elimination of synapses in neural development]. PMID- 2333364 TI - [Pineal organ: a phylogenetic aspect]. PMID- 2333366 TI - [Extracellular matrix proteins involved in synapse formation]. PMID- 2333367 TI - [Nerve growth factor]. PMID- 2333368 TI - [Glia maturation factor: the biological activity and the mechanism of action]. PMID- 2333369 TI - [Transplantation of neuronal cells in the mammalian brain]. PMID- 2333370 TI - [Regeneration of mammalian central nervous pathways]. PMID- 2333371 TI - [Collateral sprouting and formation of new synapses]. PMID- 2333372 TI - [Paraneurons in the regulation of the body]. PMID- 2333373 TI - [Brain differentiation and sex hormones]. PMID- 2333374 TI - [Neuronal cytoskeleton: molecular architecture, function and dynamics]. PMID- 2333375 TI - [Actin and actin binding proteins in neuronal tissues]. PMID- 2333376 TI - [Cholinergic neuron]. PMID- 2333377 TI - [Central monoaminergic neurons]. PMID- 2333378 TI - [The limits of psychoanalytic insight]. AB - Psychoanalysis has the intellectual power to decipher the inner structure of subjectivity, thus distinguishing itself from neighbouring human sciences. In doing so psychoanalysis is able to show the damages a society does to its individuals. Present-day psychoanalytic practice and thinking however runs counter to these inherent possibilities. The interaction of unresolvable neurotic phenomena and ideological bias in individual psychoanalysts reflect the increasing subsumption of psychoanalysis under the dominating interests of society--a dependency, which characterizes the actual psychoanalytic practice and theories in our time as basically affirmative. PMID- 2333379 TI - [The narcissism of Thomas Mann and pathologic interpretation of his homosexuality. On a "new concept" in research on Thomas Mann]. AB - On the basis of Morgenthaler's sexual theory, the author reviews Wysling's discussion of Thomas Mann's "narcissistic symptomatology" and attempts to refocus it within the external perspective of pubertal conflict. Societally organized forms of sexuality are invariably aimed at the maintenance of narcissistic equilibrium which has been jeopardized by the dissolution of the mother-infant unit. It follows that the neurotic constitution of many homosexuals results not from any hypothetical developmental disturbance in early infancy, but chiefly from the actual conflict with society. PMID- 2333380 TI - [From the devil one is not even protected in heaven. Remarks on E. Reinke's report, "Sociotherapy with prisoners", (Psyche 10/1987)]. AB - According to the author's critique, Reinke's article about the Frankfurt project for criminal offenders omits any genuine psychoanalytic reflection on the attributions of subject and object, culprit and victim, therapist and patient. Given this omission, these attributions cannot be incorporated or resolved within the intended process of change. PMID- 2333381 TI - [Questions at the general hospital. Ulcerative colitis and Crohn disease in the light of a discussion on the body and soul]. AB - The author is an internist in a non-university hospital. He discusses the possibilities and limits of dealing with patients suffering from ulcerative colitis and Crohn's disease. He demonstrates the clinical importance of a psychoanalytic perspective with three case illustrations. PMID- 2333383 TI - Anxiety and panic disorders: their diagnosis and management--I. PMID- 2333382 TI - ["The analyst and his patient". A plea for semantic sensitization in relation to sex differences within psychoanalysis]. PMID- 2333385 TI - An unusual mode of progressive motility in spermatozoa from the dasyurid marsupial, Antechinus stuartii. PMID- 2333384 TI - Development of four-cell hamster embryos to the blastocyst stage in vitro and its regulation by components of the culture milieu. AB - Constituents of the culture milieu known to influence development of hamster 2 cell and 8-cell embryos were examined for effects on the 4-cell stage. Embryos were collected at the mid 4-cell stage (approx. 45-46 h after egg activation) from superovulated females and cultured for 24 h in a chemically defined medium (TLP-PVA). As with the 2-cell stage, inorganic phosphate (Pi) strongly inhibited development of 4-cell embryos, although some (14%) were able to reach the 8-cell stage or further in the presence of Pi. However, unlike 2-cell embryos, no significant inhibitory effect of glucose on development of 4-cell embryos was found. In the absence of glucose and Pi, development of 4-cell embryos was sensitive to amino acids in the medium: the mean cell number was increased using 21 amino acids compared with 4 amino acids, similarly to the 2-cell stage; however, late blastocyst development (blastocele formation) from 4-cell embryos was reduced using 21 compared with 4 amino acids, as with 8-cell embryos. Similarly to the 2-cell and 8-cell stages, raising the CO2 concentration from 5% to 10% in the gas atmosphere for culture increased the percentage of total blastocysts developing from the 4-cell stage, but did not affect the proportions of late-stage blastocysts. These data show that 4-cell-stage hamster embryos are somewhat similar to 2-cell embryos with respect to the regulation of development by constituents of the culture milieu, but, to some extent, the 4-cell embryo is a transitional stage of development. PMID- 2333386 TI - Examination of methods for the deep freezing of goat semen. AB - In four experiments, freezing of goat semen in straws was examined and compared with conventional pellet-freezing. The optimum freezing regime was attained by holding straws in vapour 4 cm above liquid nitrogen for 30 s or longer, followed by plunging into liquid nitrogen. Straws exposed to vapour for only 10 s did not cool sufficiently before plunging, and cell viability was seriously impaired. Initiation of ice crystallization and the pattern of cooling of semen depended on size of straws and the type of rack used to hold straws in vapour during freezing. Nevertheless, semen was equally well stored in straws of 0.25 mL and 0.50 mL capacity and straws were most efficiently filled at 30 degrees C. Modified Tris media were used to dilute semen at rates (semen: diluent) of 1:2, 1:5, 1:11 and 1:23. Spermatozoa survived best in hypertonic diluents and deteriorated during post-thawing incubation in media of low tonicity, whilst the optimum diluent depended on rate of extension before freezing. The cooling curves differed markedly for semen frozen in straws in liquid nitrogen vapour and pellets on dry ice. Viability of spermatozoa was better for the pellet-frozen semen. PMID- 2333387 TI - Participation of glucose in the synthesis of glycoproteins in preimplantation mouse embryos. AB - Electrophoretic separation of solubilized embryos incubated for 24 h in the presence of [U-14C]glucose indicated incorporation of glucose carbon into a number of protein bands. Treatment of nitrocellulose blots of electrophoretograms with glucosidases had no effect on incorporated counts, confirming that the labelled bands were not due to protein bound glycogen. Furthermore, addition of 0.1 microgram mL-1 tunicamycin to the incubation medium virtually eliminated incorporation of glucose into the protein bands but had no effect on the pattern or rate of incorporation of labelled amino acids in parallel experiments. Also the pattern of labelling of protein by glucose was reflected in the pattern of binding of Con A to the nitrocellulose blots. There were quantitative and qualitative changes in labelling as development progressed. For embryos cultured from the 2-cell stage, a small amount of label was incorporated in two major bands at relative mobility (Mr) 69 and 97 K. With culture from the 8-cell stage, three additional major bands (33, 44 and 56 K) were labelled. Embryos cultured from the morula stage showed a different profile of incorporation; there was much more active labelling, and eight major and a number of minor radioactive bands were identified. Whilst tunicamycin suppressed glucose incorporation into glycoproteins and inhibited compaction of embryos, it had little effect on other parameters of metabolism during incubation in its presence for 24 h. No significant effects of the metabolite on protein synthesis, glycogen storage, lactate production or overall macromolecular synthesis were evident. By contrast, the anabolic metabolism of embryos decompacted by long periods of exposure to tunicamycin was severely reduced although glycolysis was still unaffected. Amphomycin at very high concentration (500 micrograms mL-1) was toxic to embryos but at concentrations up to 250 micrograms mL-1 had no effect on compaction and development of blastocysts. Addition of monensin to the incubation medium [16 micrograms mL-1] did not interfere with the development of either 2-cell or 8 cell embryos to blastocysts. PMID- 2333388 TI - Allocation of cells to the inner cell mass and trophectoderm of 3/4 mouse embryos. AB - The allocation of cells to the inner cell mass (ICM) and trophectoderm (TE) was investigated at 6-h intervals from 78 h to 102 h after hCG injection in 3/4 mouse embryos to determine the effect of removal of a single blastomere at the 4-cell stage on early differentiation. The procedures used to produce 3/4 embryos had little effect on embryo development. Embryos that had a single blastomere removed and then re-aggregated (RA embryos) had the same total number of cells as untreated (UT) embryos except at 78 h (P less than 0.05) and 102 h (P less than 0.01) post hCG where there were slightly less cells in RA embryos. Three-quarter embryos always had significantly fewer cells than RA embryos (P less than 0.001), with an average of 74% of the total cell number of RA embryos. As expected, 3/4 embryos always had significantly fewer cells in the ICM and TE compared with RA embryos (P less than 0.001). However, the ICM:TE ratio was also significantly lower in 3/4 embryos compared with RA embryos at 84, 96, and 102 h post hCG, indicating that the allocation of cells to the ICM and TE was disturbed. The ICM:TE ratio of 3/4 embryos could not be manipulated if either an early- or late dividing blastomere was selectively biopsied at the 4-cell stage; this suggests that the known preferential contribution of an early-dividing blastomere to the ICM is not cell autonomous. PMID- 2333389 TI - Plasma progesterone concentrations during pregnancy in the dasyurid marsupial, Antechinus stuartii: relationship with differentiation of the embryo. AB - Antechinus stuartii females were sacrificed at various stages of pregnancy timed from the first day that epithelial cell numbers declined in the urine (day 0). Embryos were recovered and their developmental stage assessed, corpora lutea (CL) were fixed for histological sections and the plasma was taken for progesterone determination. The rate of development of the embryo appeared to parallel the formation of the CL and the plasma progesterone concentrations: cleavage (less than day 6) and the expansion of the unilaminar blastocyst (less than day 14), were periods of slow development, during which the formation of the CL was incomplete and plasma progesterone was low [less than 6 ng mL-1 (19.1 nmol L-1)] though steadily increasing. After day 14 the CL reached its maximum size and plasma progesterone was maximally elevated [greater than or equal to 15 ng mL-1 (47.7 nmol L-1)] until parturition on day 27. Rapid differentiation and growth of the embryo occurred between day 22 and day 27. PMID- 2333390 TI - Roles of prolactin and the uterus in the control of luteal regression in the Bennett's wallaby (Macropus rufogriseus rufogriseus). AB - The factors responsible for controlling luteal regression in macropodid marsupials are unclear. Experiments were designed to examine the role of the uterus and the pre-partum prolactin pulse in this process. In experiment 1, two groups of adult female Bennett's wallabies were hysterectomized (n = 3) or sham hysterectomized (n = 3) on Day 16 of a non-pregnant oestrous cycle and daily peripheral blood samples were collected between Days 10-37. In both groups, circulating progesterone concentrations declined to below 0.96 nmol L-1 at luteolysis on Days 28-33. Circulating prolactin concentrations remained low over the period of luteal regression. In experiment 2, two groups of animals, which were maintained in the presence of a fertile male and synchronized by the removal of pouch young (RPY), were treated on Day 16 after RPY with a single injection of long-acting bromocriptine (Parlodel LA, Sandoz Ltd, Basle, Switzerland; 50 mg per animal n = 5) or vehicle (n = 4). Vehicle-treated animals gave birth on Day 28 (n = 3) or Day 29 (n = 1) with a significant elevation of prolactin on Day 28. In contrast, 4 of the 5 bromocriptine-treated animals failed to give birth and one gave birth on Day 29. No comparable prolactin pulse was detected in any of them. Circulating progesterone concentrations declined later in the bromocriptine treated group than in the controls. These data suggest that different mechanisms lead to luteolysis in pregnant and non-pregnant animals; in pregnancy the luteolytic signal is prolactin, whereas in the non-pregnant cycle another signal of non-uterine origin is involved. PMID- 2333391 TI - Effects of bromocriptine at parturition in the tammar wallaby, Macropus eugenii. AB - Female tammar wallabies were treated with the dopamine agonist bromocriptine at the end of pregnancy to suppress the peripartum pulse of plasma prolactin. The animals were subsequently observed, and a series of blood samples taken to define the hormonal profiles before and immediately after parturition. Birth was observed in 4/5 control animals and occurred in 8/9 bromocriptine-treated animals. The peripartum peak in plasma PGFM concentrations was not affected by bromocriptine although the pulse of prolactin normally seen at parturition was completely abolished. The timing of luteolysis was apparently unaffected, as plasma progesterone concentrations fell similarly in both treated and control animals immediately after parturition. However, all of the neonates of the bromocriptine-treated animals died within 24 h, possibly because of a failure to establish lactation. Subsequent onset of post-partum oestrus was delayed or absent both in control and in bromocriptine-treated animals, suggesting that the frequent blood sampling and disturbances in the peripartum period interfered with these endocrine processes. It is concluded that both prolactin and prostaglandin can induce luteolysis in the pregnant wallaby, but that the normal sequence of events results from a signal of fetal origin inducing a prostaglandin release from the uterus, which in turn releases a pulse of prolactin that induces a progesterone decline. PMID- 2333392 TI - Effect of continuous infusion of oxytocin on prostaglandin F2 alpha secretion and luteolysis in the cyclic ewe. AB - Circulating concentrations of 13,14-dihydro-15-keto PGF2 alpha (DHKF2 alpha), luteinizing hormone (LH) and prolactin (PRL) have been measured in cyclic ewes treated with continuous infusions of oxytocin, in order to investigate the mechanism by which the treatment delays luteal regression. Continuous infusion of oxytocin reduced prostaglandin F2 alpha (PGF2 alpha) secretion but had no detectable direct effect on LH or PRL. Oxytocin (3 nmol h-1 i.v.) given from Day 12 or 13 until Day 18 after oestrus delayed luteolysis, eight out of nine treated ewes not returning to behavioural oestrus until Day 29.1 +/- 3.2 (mean +/- s.e.m.; cycle length of control ewes 16.7 +/- 0.3 days). In the ewe in which oxytocin failed to prevent luteolysis, luteal regression had commenced before oxytocin treatment was started. In three ewes undergoing delayed luteolysis (cycle lengths, 21, 24 and 25 days) basal concentrations of PGF2 alpha (measured as DHKF2 alpha) were unchanged, but there was only one episode of PGF2 alpha secretion compared with 20 episodes in three control ewes. Prolactin secretion was pulsatile during oxytocin infusion, and levels were low following infusion in ewes with cycle length greater than 25 days while the corpora lutea were maintained. Circulating PRL concentrations were high in ewes undergoing delayed luteolysis but there was not discrete episode of PRL secretion associated with the pre-ovulatory LH surge in these animals. To investigate the possibility that the pattern of PGF2 alpha secretion was affected by depletion of oxytocin from corpora lutea, ewes previously treated with oxytocin to delay luteolysis were given a luteolytic dose of cloprostenol on Day 21 after oestrus. The amount of oxytocin secreted in response to cloprostenol was less than 10% of that seen in ewes similarly treated on Days 11-13 after oestrus. Low levels of luteal oxytocin may therefore reduce PGF2 alpha secretion in ewes undergoing delayed luteolysis. PMID- 2333393 TI - Comparison of water quality criteria and health advisories for 2,4,6 trinitrotoluene. AB - The U.S. Environmental Protection Agency (USEPA) has recently recommended health advisories (HAs) for 2,4,6-trinitrotoluene (TNT). The purpose of this brief article is to present these values so that the reader can compare them with the water quality criteria that have been proposed in another article (M. G. Ryon and R. H. Ross, 1990, Regul. Toxicol. Pharmacol. 11, 104-113). In that article, a water quality criterion of 140 micrograms/liter for TNT in drinking water was proposed, and in the present article the methodology by which USEPA calculated a lifetime HA of 2 micrograms/liter is presented. The reasons why the water quality criterion and the HA differ are discussed. PMID- 2333394 TI - Combined alcohol and other drug dependence. PMID- 2333395 TI - Structured outpatient treatment of alcohol vs. drug dependencies. AB - This chapter describes the rationale, indications, design, and use of a structured outpatient treatment approach as an effective alternative to residential treatment for alcohol and drug dependencies. An increasing demand for outpatient treatment services is being created by a combination of clinical and economic factors, including the influx of employed drug abusers who do not need or desire residential care and mounting financial pressures to contain health care costs. To be effective as a primary treatment modality, outpatient programs must be highly structured and intensive and able to deal with the full spectrum of alcohol and drug addictions. Perpetuating the historical separation between alcoholism and drug abuse treatment programs is unnecessary and counterproductive, although certain modifications in treatment approaches are needed to accommodate the distinctive characteristics of particular classes of drugs and the people who use them. The "outpatient rehab," a treatment model that approximates the intensity of inpatient treatment on an outpatient basis, may help to maximize the clinical efficacy and cost-effectiveness of outpatient treatment as a viable alternative to residential care. Initial treatment results with this model are encouraging. PMID- 2333396 TI - Operationalization of alcohol and drug dependence criteria by means of a structured interview. AB - There is growing concern worldwide about the extent of psychoactive substance abuse and dependence disorders. Epidemiological data are needed to assess the prevalence and severity of the problem. Collecting this type of data is possible with a highly structured and reliable diagnostic interview. The problems involved in developing such an interview are discussed in this chapter. They include the absence of a unified concept of psychoactive substance dependence and a lack of a standardized system of diagnostic criteria. Recently a new instrument has been designed to assess psychoactive substance abuse and dependence disorders according to multiple diagnostic systems. The WHO/ADAMHA Composite International Diagnostic Interview Substance Abuse Module (CIDI-SAM) has been found to have excellent diagnostic reliability in a test-retest pilot study. This chapter describes the development and evolution of the interview and offers guidelines for operationalization of substance abuse and dependence criteria. PMID- 2333397 TI - From basic concepts to clinical reality. Unresolved issues in the diagnosis of dependence. AB - This chapter discusses clinical and conceptual issues pertaining to the diagnosis of alcohol and drug dependence. Emphasis is given to the difficulties involved in moving from diagnostic concepts, such as those contained in the major psychiatric classification systems, to the clinical situation where diagnostic decisions are made. To illustrate how diagnostic concepts approximate clinical reality, a set of case histories is used to organize a discussion of unresolved issues in the diagnosis of dependence. These issues include the putative syndrome nature of dependence, the problem of diagnosing polysubstance use, the primary-secondary distinction, the presence of other psychopathology, and the use of multiaxial evaluation. PMID- 2333398 TI - [Recommendations on echocardiography training]. PMID- 2333399 TI - [Infective endocarditis. Medicosurgical experience in a series of 137 patients]. AB - We have reviewed our 1978 to 1987 experience in the treatment of 137 patients with 145 episodes of Infective Endocarditis. In 55 episodes the infection involved a valvular prosthesis. Positive blood cultures were obtained in 72.7%, with clear preeminence for staphylococcal organisms. Renal disfunction was associated in 41.8% of the cases and periprosthetic-leak in 40% of them. Eight patients died without surgery, five cases were cured by medical treatment alone, and 42 cases were operated, most of them because refractory heart failure. Surgical mortality was 15 cases (35.7%), with statistical significance within the early prosthetic valve endocarditis group, in which in turn was significantly greater the incidence of non-streptococcal germs, renal disfunction and periannular abscesses. The mean late follow-up was 47.6 months, including 88.8% of the surgical survivors, with a survival rate of 64.1%, being most of patients in a good functional status. In 90 episodes the infection involved a native valve, with about 40% of the cases in drug abusers. Positive blood cultures were obtained in 77.7% of the cases, with slight preeminence of staphylococcal germs. Renal dysfunction was associated in 16.6% of the cases. In 41 episodes were used only medical therapy, involving 30 of them the right side, with a death in this group. The treatment was surgical in 49 episodes, 45% of them in order to correct residual valve lesions. PMID- 2333400 TI - [Clinical and angiographic expression of myocardial ischemia in stable angina as a function of its coronary reserve]. AB - We have studied the distribution of the coronary reserve, evaluated by serial effort tests, in patients with proved coronaropathy, determining the correlation between clinic (effort and mixed angina) and coronary reserve (fixed and variable), assessing angiographic findings in function to that reserve. We took 120 patients with stable angina to whom 2 effort tests were performed, basal and after vasodilator drugs. It was considered variable reserve if in the second test the S-T descend improved greater than or equal to 1 mm for a similar of greater double product and fixed when it didn't improve. In all patients coronarography was performed. Seventy two patients (60%) showed fixed reserve, 58 with effort angina (80%) and 14 (20%) with mixed. Forty eight showed variable reserve, 40 (80%) with mixed angina and 8 (17%) with effort. The group with fixed reserve had a greater S-T max. descent (2.9 +/- 0.9 vs 2.2 +/- 0.4) (p less than 0.001), a lower double product max. (221 +/- 44 vs 284 +/- 37) (p less than 0.001) and a lower maximal oxygen consumption (MVO2 7 +/- 2 vs 11 +/- 2) (p less than 0.001) than the variable reserve group. Considering the angiography, the fixed reserve group had more number of vessels affected (1.9 +/- 0.7 vs 1.4 +/- 0.5) (p less than 0.01), a higher angiographic score (4.88 +/- 2.4 vs 2.2 +/- 1.2) (p less than 0.001), a lower ejection fraction (59 +/- 8.5 vs 65 +/- 7.5) (p less than 0.001), more multivessel and descending anterior artery lesion than the variable reserve group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333401 TI - [Infarct size determination using enzymatic methods in patients with early coronary recanalization]. AB - To evaluate the usefulness of the infarct size determined by serial creatine kinase (CPK) measurements in patients with early reperfusion, we have studied 189 patients meaning in age 59.2 +/- 8.6 years, with acute myocardial infarction treated with streptokinase (STK); 81 of them by intracoronary route (group A), and 108 by intravenous administration (group B). In the group A we performed serial angiographic studies in the following conditions: baseline, immediately after STK infusion and before hospital discharge. In group B we performed only one angiographic control 5 +/- 3 days after. In patients with reperfusion, the parameters of left ventricular function correlated with cumulative creatine kinase release (MAX-CPKr) by linear regression in both groups. We observed a tendency to closer correlations in patients with left anterior descending or circumflex artery as the infarct related artery, in patients without previous infarction and in those who did not receive electrical shock for ventricular arrhythmias. In patients with unsuccessful reperfusion (n = 11), we also obtain a significant correlation (r = 0.72) between ejection fraction and MAX-CPKr. The slope of the regression line (b = 7.7 X 10(-5) was steeper (p less than 0.05) than that observed in recanalized patients, who were evaluated within the first 3 days (b = 2.2 X 10(-5), after 8 +/- 5 days (b = 2.7 X 10(-5), or before discharge, at 22 +/- 9 days (b = 2.6 X 10(-5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333402 TI - [Circumferential profiles versus visual analysis in studies of myocardial perfusion during exertion using thallium-201]. AB - Two methods of analysis for perfusion myocardial studies with thallium are compared: the conventional visual analysis, and a quantitative method which shows results as circumferential profiles. Three hundred and ninety myocardial segments in 65 patients were studied. Visual analysis showed abnormalities in 44/65 (68%) patients, the quantitative method did it in 53/65 (81%). When localization and/or extension discrepancy between the two methods was found, angiography was always concordant with circumferential profiles findings. Total agreement between the two methods was present in 20/65 (31%) patients. The quantitative method is more sensitive than the visual analysis. It is also more precise in defining localization and extension of thallium defects. PMID- 2333403 TI - [Multiple aneurysms of the left auricula, ascending aorta and sinuses of Valsalva with interventricular communication, fibromuscular subaortic stenosis and a single coronary artery]. AB - We report the case of a male newborn infant with aneurysm of atrial appendage, ascending aorta and sinus of Valsalva associated to ventricular septal defect, fibromuscular subaortic stenosis and single coronary artery. The diagnosis was carried out by means of two-dimensional echocardiography and angiocardiography. This complex cardiac malformation has not been reported before. PMID- 2333404 TI - [Atrioventricular block in Kearns-Sayre syndrome]. AB - We report a case of a 17-year-old woman with Kearns-Sayre Syndrome who developed a high degree atrioventricular block. She had intraventricular conduction disturbances with normal atrioventricular conduction in previous electrocardiograms. The diagnosis criteria of this rare syndrome are commented on, and we describe the electrophysiological features, prognostic and treatment that atrioventricular conduction disturbances produce in these patients. We emphasize the necessary collaboration between neurologists and cardiologists in the early recognition of the conduction disturbances for implanting a prophylactic pacemaker. PMID- 2333405 TI - [Severe pulmonary arterial hypertension caused by protein C deficiency reversible after medical treatment]. AB - We report the case of a young man with severe pulmonary hypertension caused by multiple thromboembolism subsequent to congenital protein C deficit. During the previous phase to haematological treatment we showed a very poor response to vasodilators evaluated by Doppler-Echocardiography. The etiological diagnosis was confirmed and initialized the anticoagulant treatment. We had observed a significant regression of peak gradient atrioventricular by continuous wave Doppler and a complete clinical normalization. PMID- 2333406 TI - [Acute myocardial infarct in a cocaine-addicted young man]. AB - We present a case of acute myocardial infarction in a 22 year old cocaine user. The absence of coronary artery stenotic lesions, as was seen in the coronary arteriography, and the absence of personal past cardiovascular or family history, suggest a cocaine-induced coronary spasm as responsible for the acute myocardial event. PMID- 2333407 TI - [The single coronary artery. Presentation of a case]. AB - A patient with a single coronary artery originating in the right coronary sinus is presented. The condition was diagnosed during aortic valve replacement surgery and later confirmed by coronary angiogram. The clinic significance in relation to the anomalous course of the coronary artery and the importance of correct diagnosis prior to cardiac surgery is discussed. PMID- 2333408 TI - The effect of carbamoylpiperidine and nipecotoylpiperazine analogs on ADP stimulated human thrombocyte aggregation and platelet factor 3 availability. AB - There is a striking congruence between the inhibitory effects of three synthetic entities on ADP-induced (i) human blood platelet aggregation and (ii) platelet factor 3 availability as evidenced by prolonged 'Stypven time'. The pronounced parallel between each compound's potency in inhibiting aggregation (e.g. IA 48.9 +/- 1.3, S.E., %; n = 16) and in impeding platelet factor 3 availability (e.g. IPF-3av 42.3 +/- 2.5, S.E., %; n = 12), determined concurrently in platelet-rich plasma of four different donors, further substantiates that the antiplatelet activity of our carbamoylpiperidine and nipecotoylpiperazine congeners is exerted through their interaction with anionic phospholipids. PMID- 2333409 TI - Production and release of platelet-activating factor by the injured heart-muscle cell (cardiomyocyte). AB - The potential of the injured heart-muscle cell (cardiomyocyte) to produce platelet-activating factor (PAF) has been evaluated. Beating rat myocytes in primary monolayer culture were used as the study-object, and metabolic inhibition served as the injury stimulus. Coincident with the development of irreversible injury, myocytes evidenced a rapid, net production of PAF which was sustained for some 3-6 h and reached, maximally, low-ng levels within approximately 0.5 h of injury. In the presence of serum, much of the PAF was released from the injured myocytes, whereas under serum-free conditions the PAF remained largely intracellular. Cardiomyocyte-derived PAF was pro-aggregatory to platelets and displayed the chromatographic properties and chemical reactivity of authentic PAF. However, PAF itself did not elicit myocyte injury, and a specific PAF antagonist could not attenuate the myocyte damage associated with metabolic inhibition. These results suggest that the cardiomyocyte may constitute a cellular source of PAF during heart injury, although the cell itself is not directly responsive to PAF. PMID- 2333410 TI - In vivo and in vitro cholinesterase inhibitor property of the antitumor agent caracemide. AB - The antitumor agent caracemide [N-acetyl-N-(methylcarbamoyloxy)-N'-methylurea] has been observed to induce signs of cholinergic activation in both animal and human studies at high clinical and toxic levels. The present study was designed to further characterize the ability of caracemide to inhibit cholinesterase both in vivo and in vitro. Caracemide produced a time-dependent inhibition of purified acetylcholinesterase, pseudocholinesterase and rat brain homogenate cholinesterase with IC50 values of 0.60, 0.55 and 17.8 microM, respectively, at the maximal time point of inhibition. Analysis of Lineweaver-Burke plots derived from inhibition of brain homogenates revealed predominantly competitive type inhibition at both initial and maximal incubation times. Intravenous administration of caracemide to rats resulted in a dose-dependent inhibition of brain cholinesterase activity, with the greatest inhibition occurring in the cortex. PMID- 2333411 TI - The effect of carbon monoxide on the function of a crustacean sensory receptor is no different to the effect of hypoxia. AB - The crayfish Cherax was used as a model to determine whether there are behavioural and neural effects that can be attributed to a direct carbon monoxide toxicity rather than to the hypoxia it produces. A comparison was made by replacing the oxygen in the ambient liquid with carbon monoxide or with nitrogen. We found that Cherax is resistant to extreme hypoxia produced by either gas, and that there is therefore no meaningful behavioural carbon monoxide toxicity. We describe hypoxia-induced changes in the tonic and phasic activity recorded from in-vitro preparations of the muscle receptor organs that are the same for nitrogen and carbon monoxide substituted saline solutions. We conclude that in the single cells of the muscle receptor organs of Cherax, carbon monoxide has no toxic effects additional to those attributable to hypoxia. PMID- 2333412 TI - Comparison of intravenous and nasal bioavailability of clonidine in rodents. AB - The bioavailability and cardiac depressant activity of 3H-clonidine was studied following intravenous and nasal administration in rodents. The drug is rapidly absorbed by nasal route, and the peak blood concentration is reached within 10 minutes. The area under the blood concentration-time curve, following intravenous and nasal routes, was found to be 3.55 x 10(5) counts/g/min and 3.75 x 10(5) counts/g/min respectively. The drug was found to eliminate slowly from blood. The t1/2 beta, following intravenous and nasal administration, was found to be 8.8 hr and 8.0 hr respectively. Our electrocardiographic studies, to compare myocardial depression following intravenous and nasal administration of clonidine, revealed that a bolus intravenous clonidine in the dose of 10 micrograms, 30 micrograms, and 100 micrograms/kg body weight produced a significant and transient decrease in heart rate in a dose dependent manner. One rat developed arrhythmia after receiving a higher dose of 100 micrograms/kg body weight of clonidine by intravenous route. However, only a mild decrease in heart rate was observed following nasal administration of clonidine. The examination of the nasal cavity one hour after the single dose of 100 micrograms/kg body weight of clonidine in rats showed no sign of erythema, oedema or lesions. These findings suggest that the nasal route may be a good substitute for I.V. administration of clonidine. PMID- 2333413 TI - Effect of N-benzyl-D-glucamine dithiocarbamate on lipid peroxidation in testes of rats treated with cadmium. AB - The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on lipid peroxidation in testes, liver, and kidney of rats after cadmium injection was studied. Rats were injected subcutaneously with 5 mg CdCl2/kg and 30 min later they were injected intraperitoneally with BGD (400 mumol/kg). Cadmium treatment resulted in a significant increase in the lipid peroxidation in these organs, with a particularly remarkable increase in the testes. The increased lipid peroxidation in these organs was decreased to the control level by BGD injection after cadmium treatment. The lipid peroxidation in microsomes in testes was significantly increased compared to that of the control. BGD treatment significantly decreased the cadmium concentration in the microsomes in testes of cadmium-treated rats. The lipid peroxidation in liver and kidney microsomes was little changed. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the testes, liver, and kidney were little changed by cadmium treatment. The catalase activity in the testes was increased after cadmium injection and BGD treatment significantly decreased the increased enzyme activity. These results suggest relatively small contribution of SOD, GSH-Px, and catalase in cadmium-induced lipid peroxidation in the testes. The depressive effect of BGD on the increased lipid peroxidation in the testes of rats treated with cadmium may be in part related to the decrease in the cadmium concentration in the microsomes in testes. PMID- 2333414 TI - Nickel binding by isolated human trophoblast cells. AB - Isolated human trophoblast cells were used for the first time to mimic the placental metabolism of nickel. The retention of nickel by the trophoblast cells was assessed in presence of different nickel ligands. Nickel chloride and nickel albumin showed an initial rapid binding to human trophoblast cells reaching a quasi-steady state after 30 min. Albumin, however, reduced the binding of nickel to the cells. Nickel-histidine showed slow initial binding, although no saturation was achieved. The results for nickel-histidine complexes are similar to those observed in in vivo experiments. PMID- 2333415 TI - Multiple molecular forms of rat liver glucose-6-phosphate dehydrogenase during liver hyperplasia induced by lead nitrate. AB - In the present study the three dimeric molecular forms of rat liver glucose-6 phosphate dehydrogenase were investigated during liver hyperplasia induced by lead nitrate. An increase of band 3 and a concomitant decrease of band 1 was found, indicating that this proliferating process is characterized by a peculiar pattern in the distribution of liver G6PD activity. Since the same pattern was observed also in liver hyperplasia induced in fasted animals, a condition otherwise characterized by a shift towards band 1, we suggest that during proliferating processes the metabolic control normally exerted by fasting on the enzymatic activity is overcome. PMID- 2333416 TI - Protection by pantethine, pantothenic acid and cystamine against carbon tetrachloride-induced hepatotoxicity in the rat. AB - The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine (50 mg/kg) for 5 days conferred significant protection against the hepatotoxic and peroxidative actions of a 0.5 mL/kg ip dose of CCl4 in rats. All three treatments lessened the increases in serum ALT and liver TBARS values, and the reductions in serum triglyceride levels, and prevented the development of hepatic steatosis caused by the halocarbon. Pantethine was found to offer the greatest protection. PMID- 2333417 TI - Lack of effect of verapamil and MDL 646, a cytoprotective PGE1 analogue on cyclosporin A nephrotoxicity in vitro. AB - Nephrotoxicity is the most troublesome side effect of cyclosporin A (CSA) therapy. In vitro studies have shown that verapamil and PGE analogues can protect human and rat kidney allografts and murine pancreatic B cells from CSA cytotoxicity. The LLC-PK.1 pig kidney cell line has recently been shown to be a use-ful in vitro model system for studying CSA nephrotoxicity. We have adopted the MTT assay to assess the effects of CSA on LCC-PK.1 cell growth and have examined the effects of verapamil and MDL 646, a cyto-protective PGE1 analogue, on CSA nephrotoxicity. The results show that neither compound prevents the cytotoxic effects of CSA on kidney cells. PMID- 2333418 TI - A quantitative structure-activity relationship study for local anesthetic activity of mono-and diaryl-2-quinuclidinylcarbinols. AB - The local anesthetic activity of a series of arylquinuclidinylcarbinols is shown to be significantly correlated with their lipophilic character, suggesting that lipophilicity is an important factor for the local anesthetic action of drugs. PMID- 2333419 TI - Effect of age on sensory nerve conduction velocity in the horse. AB - This study aimed to establish a clinically reproducible method of evaluation of sensory nerve conduction in the horse and to provide reference values in a group of normal horses. Age-related changes in the sensory nerve conduction velocity were of particular interest. Sensory nerve conduction was performed in the lateral palmar nerve. The results revealed an increase in velocity over the first year of life and a subsequent decrease in velocity in older horses. The effect of age must be considered if results from horses in which peripheral nerve disease is suspected are to be interpreted correctly. The results reflect similar findings in man and other domestic species. PMID- 2333420 TI - Quantitative and qualitative morphology of equine peripheral nerve: teased fibre studies. AB - Single teased fibre studies were made on samples of the lateral palmar nerve from 16 horses of mixed age and size which had no evidence of neuromuscular disease. Significant proportions of abnormal fibres indicative of axonal degeneration/regeneration and demyelination/remyelination were identified. Measurements of internodal length and fibre diameter were made. Internodal length was shown to be related to fibre diameter, changes in this relationship being mainly influenced by the incidence of abnormal fibres rather than by the age of the horse. Information about the incidence of abnormal fibres in normal horses is required if findings in biopsy material are to be interpreted correctly. PMID- 2333421 TI - Influence of gestation on the pharmacokinetics of four sulphonamides in goats. AB - The influence of gestation on the pharmacokinetics of four sulphonamides was studied in goats before, during and after pregnancy. Similar doses were given as intravenous boluses of 50 mg kg-1 each. Results were compared with those of non pregnant goats to eliminate seasonal effects. With sulphadimidine elimination was mainly apparently first-order. In gestating goats the mean residence times decreased and mean plasma clearance rates increased with sulphadimidine during pregnancy, but this effect was continued after kidding at least until the end of May. The same happened with sulphadimethoxine, but sulphisomidine was not affected. In contrast to the other sulphonamides the mean residence time of sulphadoxine showed a maximum in February in gestating goats, while mean plasma clearance remained constant during and after pregnancy, at a lower level than in September. The mean plasma clearance of sulphadoxine decreased significantly from September to February in the non-pregnant control goats. In May five of six control goats and two of six goats which had kidded showed capacity-limited elimination against only two control goats in the foregoing experiments. With sulphadoxine one animal in the gestation group, but not the same one in each experiment, showed capacity-limited elimination against one, four and three in the control group in December, February and May, respectively. Distribution volumes increased significantly during and after pregnancy with sulphisomidine and sulphadimethoxine. A decrease in distribution volumes was seen in control goats with sulphadimidine, sulphisomidine and sulphadoxine, but was only significant for sulphadoxine. The pregnant uterus could not be recognised as an extra compartment, either in distribution volume nor in the pharmacokinetic model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333422 TI - Vitamin E concentrations in blood plasma of sheep and in sheep tissues after a single intraruminal or intraperitoneal administration of DL-alpha-tocopheryl acetate. AB - Twenty-five yearling wethers, weighing 40 to 45 kg were used in a trial designed to compare the effect of the route of administration of vitamin E upon plasma and tissue vitamin E status. Five control sheep without vitamin E administration were killed at the beginning of the trial. Of the remaining 20 sheep, 10 were given DL alpha-tocopheryl acetate intraruminally and 10 by intraperitoneal injection. Of these, 10 wethers were killed three days after dosing (five from each treatment, IR3 and IP3) and the remaining wethers were killed eight days after dosing (IR8 and IP8). Blood samples were taken throughout the trial from sheep on the IR8 and IP8 treatments. Samples of whole adrenal gland, heart, liver, kidney, brachiocephalicus muscle, lung, pancreas and spleen were taken from all sheep at slaughter and were analysed for their vitamin E content. The blood plasma results showed that the most important index of vitamin E bioavailability, the area under the plasma concentration versus time curve, was greater in the intraperitoneally than intraruminally dosed sheep. There was a higher concentration of vitamin E in the tissues from the intraperitoneal group than the intraruminal group three days after the intraperitoneal injections. The results suggest that the greatest responses in vitamin E concentration in plasma and the tissues were recorded in sheep following intraperitoneal rather than intraruminal dosing with DL-alpha tocopheryl acetate. PMID- 2333423 TI - Effects of amitraz on nerve conduction and neuromuscular transmission in anaesthetised dogs. AB - Ataxia is an occasional side effect of amitraz when used as a wash to treat dogs with demodectic mange. In the present study, successive doses of 0.5, 2, 5 and 10 mg kg-1 amitraz were given intravenously at intervals of nine minutes to thiopentone/methoxyflurane/oxygen anaesthetised dogs. The amplitude of the evoked muscle action potential to electrical stimulation of the right ulnar nerve and the muscle refractory period were unchanged by increasing doses of amitraz but there was a progressive and significant decrease in nerve conduction velocity. The minimum recorded nerve conduction velocity (50.7 +/- 1.5 m s-1) was still within an adequate range. From these results it appears that the ataxia following amitraz is unlikely to be attributable to peripheral mechanisms. The concurrent amitraz-induced rise in mean arterial pressure and bradycardia was consistent with previous findings in which alpha 2-adrenoceptors were shown to be the major mediators. PMID- 2333424 TI - Serum lipids and lipoproteins in equine colic and grass sickness. AB - Serum total lipids, lipoprotein fractions, triglycerides, cholesterol, phospholipids and free fatty acids were measured in horses with acute, subacute and chronic grass sickness (equine dysautonomia) and in colic cases. The values were compared with those of normal grazing and stabled horses. A marked individual variation occurred, but total lipids, triglycerides and free fatty acids were significantly higher than normal in grass sickness and colic cases with cholesterol was significantly higher than normal in grass sickness cases only. Pre-beta lipoprotein was significantly increased in colic and subacute grass sickness although all abnormal groups showed this fraction which was absent from normal horses. The percentage of alpha 2b lipoprotein was significantly higher in colic and grass sickness. The changes described are typical of those occurring in fat mobilisation in the horse and are considered to be due to a number of factors including decreased food intake, cortisol and catecholamine release and insulin resistance. PMID- 2333425 TI - In vitro activity of chloropolysporin-C, a new glycopeptide-group antibiotic, on Clostridium perfringens isolates and its in vivo activity against C perfringens and other intestinal microflora of the caeca of broiler chickens. AB - The influence of chloropolysporin-C, a new glycopeptide antibiotic, on in vitro activity of Clostridium perfringens isolates and its effects on the intestinal microflora of broiler chickens was examined. The in vitro sensitivity of 88 isolates of C perfringens to four antimicrobial agents, including chloropolysporin-C, was tested by an agar dilution method. The antibiotics used all had minimum inhibitory concentration levels of 6.25 micrograms ml-1 or less against this organism. Changes were examined in the intestinal microflora of broiler chickens fed a diet containing chloropolysporin-C to obtain basic data on the mechanisms by which the antibiotic aided livestock production. No clinical findings were recognised in chickens tested during the period of antibiotic administration. A decrease in viable cells of the clostridia was the principal response recognised during the period of drug administration in feed. Among the other microflora, chloropolysporin-C led to a significant response among Gram positive bacteria, but no changes in the total bacterial count. PMID- 2333426 TI - Interspecies variation in the plasma halflife of oxytetracycline in relation to bodyweight. AB - The relationship between halflife (t1/2, minutes) of oxytetracycline and bodyweight (W, kg) between species of mammals and birds was examined using data collected from the literature. Linear regression of the logarithm of the halflife of the elimination phase of oxytetracycline following intravenous injection on the logarithm of bodyweight for a variety of species of mammals and birds revealed a significant correlation between species (r = 0.602, n = 13, P less than 0.05). The interspecies relationship was described by the allometric equation; t1/2 = 160 W0.20. This suggests that there is about a 14-fold variation in t1/2 across the size range of terrestrial homoeotherms, and provides a guide to dosage regime for species in which oxytetracycline kinetics have not been studied. PMID- 2333427 TI - Pathophysiological and parasitological studies on a concurrent infection of Ostertagia ostertagi and Cooperia oncophora in calves. AB - Calves which had received daily concurrent infections of 2000 Ostertagia ostertagi and 10,000 Cooperia oncophora infective larvae over a 42-day period displayed a range of clinical signs typical of acute parasitic gastroenteritis including inappetence, weight loss, hypoalbuminaemia and diarrhoea. There were consistent and significant depressions in both digestive efficiency and nitrogen retention. Radioisotopic studies revealed marked disturbances in protein metabolism which were associated with high losses of plasma proteins into the gastrointestinal tract. On post mortem examination larval establishment of O ostertagi was seen to be high. The adverse changes were prevented by the prior administration of a morantel bolus. PMID- 2333428 TI - Morphology of medullary bone during the egg formation cycle. AB - The medullary bone of birds is known to function as a calcium store for egg shell production, but it is not known if the stage of shell formation within the egg formation cycle is reflected by the thickness of osteoid seams on the medullary bone. Adult laying hens were killed at two points in the formation cycle to determine the effects of shell formation on medullary bone using histological techniques. No differences in medullary bone volume or osteoid thickness were apparent at either of the two points. Fluorochrome bone labelling techniques demonstrated, however, that less medullary bone mineralisation occurred during the active period of shell formation. PMID- 2333429 TI - Effect on liver function of acetonaemia and the fat cow syndrome in cattle. AB - The effect of fatty infiltration on liver function was studied in 29 dairy cows aged 6 +/- 0.4 (SEM) years with primary acetonaemia, secondary acetonaemia or the fat cow syndrome. The average interval from calving at diagnosis was 16.4 +/- 2.0 days and the animals had been anorexic for a mean of 5.6 +/- 0.8 days. Fatty infiltration of the liver occurred well before calving and was associated with severe clinical illness and intercurrent infections. The percentage of fatty infiltration in the liver (mean 53.1 +/- 2.8 per cent) was significantly correlated with both the degree of clinical illness (P less than 0.001) and the period of anorexia (P less than 0.05). Alterations in uptake, conjugation and excretion at the hepatocyte level were determined by measuring bromsulphthalein clearance, and plasma total bilirubin and total bile acid concentrations. Values for all three were positively correlated with the extent of fatty infiltration. Plasma albumin, urea and glucose concentrations were reliable indicators of the liver's synthetic function and together with plasma aspartate aminotransferase, iditol and glutamate dehydrogenase were correlated with the degree of hepatic lipidosis. PMID- 2333430 TI - Comparative pharmacokinetics of amikacin sulphate in calves and sheep. AB - The pharmacokinetics of amikacin sulphate were investigated in calves and sheep. Five animals of each species were given 7.5 mg kg-1 intravenously and intramuscularly. After intravenous administration the pharmacokinetic parameters significantly different (P less than 0.01) between calves (first value) and sheep (second value), were: the initial concentration (87.05, 146.6 micrograms ml-1), the apparent distribution volume (350, 200 ml kg-1), the area under curve (5512, 11,018 min micrograms ml-1) and the clearance (1.5, 0.7 ml min-1 kg-1). After dosing intramuscularly the peak concentration (23.5, 34.36 micrograms ml-1), the peak time (45, 75 min) and the area under curve (5458, 9191 min micrograms ml-1) were significantly different (P less than 0.01). No significant differences were observed in the terminal halflife values, suggesting that elimination rate was independent of both route of administration and animal species. The drug in aqueous solution showed a good bioavailability in both animal species (about 0.87 in sheep and greater than 0.99 in calves) despite the greater serum concentrations always attained in sheep. PMID- 2333431 TI - Phototoxicity of olaquindox in the rat. AB - Because of its photoallergic properties quindoxin, a growth promoting feed additive used for example in cattle raising, has been taken off the market. Recently, it appeared that the quindoxin derived olaquindox (OLAQ), used for the same purpose, also produces these light-induced side effects. In this study, phototoxicity of OLAQ was investigated by comparing four groups of rats with a different daily regime: 1 = light plus OLAQ, 2 = dark plus OLAQ, 3 = light (no OLAQ), 4 = dark (no OLAQ). It appeared that rats of group 2 excreted per day approximately 60 per cent of their daily dose as OLAQ and approximately 2 per cent as OLAQ-4-monoxide, whereas these figures were approximately 19 per cent and 30 per cent, respectively, for the light-exposed animals. Besides, rats of group 1 only, suffered from severe erythema, oedema and necrosis of the ears after four days treatment. It is probable that OLAQ, photoactivated in the skin, forms a reactive oxaziridine, analogous to what has been found with the tranquilliser chlordiazepoxide (Librium; Hoffmann La Roche), another imino-N-oxide. PMID- 2333432 TI - Pharmacokinetics of pethidine administered intramuscularly and intravenously to dogs over 10 years old. AB - The pharmacokinetics of pethidine administered postoperatively both intravenously and intramuscularly was investigated in dogs aged over 10 years. When the drug was given intravenously (2 mg kg-1), plasma levels declined in a biexponential manner, with an elimination half-life of 62.7 minutes. Following its intramuscular administration at the same dose rate, absorption was very slow and two distinct rates of absorption were observed. Maximum plasma concentrations were not achieved until 33 minutes after drug administration. The elimination of the intramuscularly administered drug was also slow with a t 1/2 beta' of 145.9 minutes. Thus, it seems that in elderly animals pethidine has a long elimination half-life and a slowed rate of absorption. However, the total body clearance of the drug does not seem to be affected by age. PMID- 2333433 TI - The neuropathic oesophagus. A radiographic and manometric study on the evolution of megaoesophagus in dogs with developing axonal neuropathy. AB - Dogs given the neurotoxin acrylamide develop peripheral neuropathy and megaoesophagus. Sequential radiographic and manometric studies on the oesophagus demonstrated that the initial abnormalities consisted of a progressive decrease in the proportion of swallows that initiated peristalsis and a gradual increase in oesophageal calibre. Regurgitation, peristaltic failure and oesophageal dilatation all appeared within three days. The eating behaviour and gait abnormalities quickly resolved on stopping the neurotoxin, but the oesophagus remained dilated for longer. Previous studies have suggested that the abnormalities present in dogs which are developing a distal axonal neuropathy or in some dogs with idiopathic megaoesophagus may be limited to the proprioceptive elements of the oesophageal innervation. The present study suggests that the progressive inefficiency in the transmission of swallows and changes in oesophageal calibre in dogs with evolving megaoesophagus may be a consequence of damage to these proprioceptive elements. PMID- 2333434 TI - Trisomy D2 in a feline neurofibroma. AB - An eight-year-old female cat developed a skin neurofibroma. The cytogenetic evaluation of the tumour cells showed the presence of a high percentage (16.4 per cent) of trisomic cells. The trisomy concerned chromosome number D2. PMID- 2333435 TI - Follicle characteristics of non-woolly Indian goats. AB - Skin follicular studies of four non-woolly Indian goat breeds are reported. The number of primary follicles ranged from 2 to 14 mm-2 with an overall mean of 6.40 +/- 0.22. Secondary follicles per mm2 ranged from 1 to 23 with an overall mean of 9.48 +/- 0.55. The secondary/primary follicle ratios (S/P) for Black Bengal, Jamnapari, Barbari and Sirohi goats were 1.57 +/- 0.21, 1.15 +/- 0.16, 1.61 +/- 0.21 and 2.04 +/- 0.21, respectively, with an overall mean of 1.59 +/- 0.99. The corresponding values for the total follicles per mm2 for the four breeds were 16.83 +/- 1.39, 15.86 +/- 1.08, 17.66 +/- 1.41 and 13.19 +/- 1.41 with an overall mean of 15.88 +/- 0.66. Per cent primaries were lowest in Sirohi and highest in Jamnapari goats. Analysis of variance revealed significant differences between breeds for the number of primary follicles and S/P ratio. Sex differences and the interaction between breed x sex were not significant for any of the follicle traits studied. On the basis of follicle characteristics the non-woolly short haired goats offer a reasonable scope for crossing with fibre goats, and Sirohi goats possibly have better skin quality for leather conversion than other goat breeds studied. PMID- 2333436 TI - Efficacy of paraherquamide against immature Trichostrongylus colubriformis in the gerbil (Meriones unguiculatus). AB - Paraherquamide was 98 to 100 per cent effective against six-day-old Trichostrongylus colubriformis infections in gerbils when given as single oral doses of 1.56 mg kg-1 and above. Doses of 0.78 or 0.39 mg kg-1 were 96 and 66 per cent effective, respectively. A single oral dose of 200 mg kg-1 was well tolerated. PMID- 2333437 TI - An enzyme-linked immunoassay for the measurement of the concentration of cortisol in sheep plasma. AB - An enzyme-linked immunoassay has been adapted for the assay of cortisol in sheep plasma. The results are similar to those obtained by radioimmunoassay but an enzyme-linked immunoassay does not require the use of radioactive compounds or expensive equipment to measure radioactivity. PMID- 2333438 TI - Detection of Mokola virus neutralising antibodies in Nigerian dogs. AB - Five hundred healthy Nigerian dogs were randomly selected and bled for serological detection of antibodies to lyssa-viruses, including Mokola, Lagos bat and Duvenhage viruses. The canine sera were screened for virus neutralising antibodies by a modification of the rapid fluorescent focus inhibition technique. Three serum samples were seropositive to Mokola virus but all were negative to Lagos bat and Duvenhage viruses. The three seropositive Mokola samples were also negative for rabies virus neutralising antibodies. This finding may explain occasional rabies-like canine mortalities within one year of antirabies vaccination in Nigeria. PMID- 2333439 TI - Liquid flow and capacity of the caecum and colon of the horse. AB - The rate of flow of fluid from the caecum and from the large colon was measured in four Shetland-type ponies fed a hay diet. In two ponies with cannulas in the caecum and at the origin of the right ventral colon, a continuous intracaecal infusion of a solution of chromium EDTA was used and samples were obtained from the cannula at the origin of the right ventral colon. Based on four determinations, the liquid flow from the caecum was 54.2 +/- 1.89 litres d-1. In the other two ponies with cannulas in the origin of the right ventral colon and near the end of the right dorsal colon, a continuous infusion of chromium EDTA was made into the right ventral colon and samples were obtained from the right dorsal colon. The flow rate towards the end of the dorsal colon was 49.4 +/- 1.25 litres d-1, based on four determinations. The capacities of the caecum and large colon after death were 7.0 +/- 0.8 and 17.7 +/- 3.7 litres, respectively. PMID- 2333440 TI - [Delayed Sumithion intoxication]. AB - A case of delayed Sumithion (fenitrothion) intoxication is reported. A 52-year old man ingested 10 ml of Sumithion in order to commit suicide with alcohol and triazoram. Several hours later, he was admitted to our hospital because of clouding consciousness. On admission, he was somnolent, but had no other symptoms, especially suggested organophosphorus intoxication. After 40 hours, fasciculation and salivation, which are early symptoms of organophosphorus intoxication, gradually appeared. The concentration of Sumithion in the blood was measured during the course and its metabolism was represented phalmacokineticaly by a 2-compartment model. The retarded metabolism of the Sumithion was suggested by this model. It is considered that the retarded metabolism of Sumithion caused the delayed intoxication. PMID- 2333441 TI - Scanning electron microscopic examinations of microvascular casts of the rat liver and bile duct. AB - Microvascular features of normal rat livers and bile duct system were examined with the vascular casts using methacrylated resin. Portal vein branches not only showed regular tapered down bifurcations but also had many side branches, some of which were directly connected with sinusoids. Terminations of hepatic arterial branches were divided into three types: 1) Many branches pouring into peribiliary capillary plexus (PBP), 2) branches directly pouring into periportal sinusoids and/or peripheral portal vein branches via arterio-portal anastomoses, and 3) anastomoses with periportal vascular plexus. PBP was composed of rich vascular networks. In large portal tracts, the plexus showed two layers, that is, the inner layer made up of a close network of capillary vessels and the outer layer consisting of a loose network of arteries and veins, while the PBP in the small portal tracts was composed of only a single layer of loose capillary network. Transitional features of these two patterns were found in the medium-sized portal tracts. PBP was supplied by afferent vessels from the interlobular hepatic artery as described above, and were directly connected with interlobular branches of the portal vein (internal root). The extrahepatic bile duct revealed a much richer vasculature than the intrahepatic bile duct. Both arterial and venous branches were ramified at almost right angle from a pair of arteries and veins running parallel with the bile duct. Occasional strictures, which might have been sphincter portions of the media, were noted at the branching sites of the artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333442 TI - A passive tobacco smoke exposure system for laboratory animals. AB - A simple passive tobacco smoke exposure system was developed for laboratory animals. The system consisted of a tobacco smoke generator and an exposure chamber. Performance testing was conducted using Fischer 344 rats. The rats were exposed to passive tobacco smoke generated by 20 cigarettes per day for 3 months. The concentration of the cigarette smoke aerosol (particle phase) in the chamber can be kept almost constant during exposure. The daily average mass concentration was 10.0 +/- 4.3 mg/m3 and the carbon monoxide was 79 +/- 22 ppm during exposure. PMID- 2333443 TI - [Distribution pattern of Dirofilaria immitis microfilariae in peripheral blood of a dog and their intake by mosquitoes]. AB - Experiments were made in which Aedes aegypti mosquitoes fed on a dog infected with Dirofilaria immitis, in order to determine the distribution pattern of microfilariae (Mf) in the dog's periphery blood and the number of Mf taken by the mosquitoes. Mosquitoes fed on an anesthetized dog at some 50 shaved skin spots and they were weighed immediately before and after feeding. This enabled us to examine not only the Mf number taken by each mosquito but also the Mf intake density in terms of Mf number per mg of blood. The Mf intake density showed a wide variation at the different parts of the dog's body, and the frequencies of Mf showed uneven distributions which were fitted best by the negative binomial. Significant differences were detected in the Mf intake density at different parts of the skin, but these differences were concluded as a non-consistent result because a similar result was not reproduced in the next experiment. It was presumed that not only the Mf number per mosquito but also the Mf intake density increased as the blood intake by the mosquitoes increased. This increase of both the Mf number per mosquito and the Mf intake density was also supported by another experiment in which mosquitoes were fed at the same skin spots consecutively one after another. PMID- 2333444 TI - [Analysis of factors associated with the occurrence of low birth weight infants]. AB - The relationship between low birth weight infants (LBW) and 3 perinatal factors; pre-pregnant maternal Body Mass Index (BMI: Quetelet's index), maternal height and parity was investigated by the log-linear analysis, using the birth records of an obstetric facility at Naha city. In this facility there were 4,894 deliveries from Jan. 1978 to Dec. 1987. Of the 4,894 infants, 4,142 were live singletons with available data for the analysis. The odds ratio of each risk factor was calculated by the log-linear model. Women with lower pre-pregnant BMI (less than 20) had an increased LBW risk by 1.80 (95% CI: 1.32-2.43) compared to women with higher pre-pregnant BMI (20 less than). Lower maternal height (150 cm greater than) was associated with significant LBW risk (1.47; 95% CI: 1.03-2.12). Primiparae had higher LBW risk than multiparae (1.68; 95% CI: 1.25-2.28). In this analysis we evaluated the interaction effects on LBW occurrence of the three factors and found no interaction effects among them. PMID- 2333445 TI - [Validity of daily energy expenditure estimated by calorie counter combined with accelerometer]. AB - To estimate a reasonable and convenient method for the assessment of daily energy expenditure in workers, the validity of a calorie counter combined with an accelerometer (Kenz Calorie Counter) was tested during treadmill exercise. Ten male and female students each volunteered for exercise on a treadmill at different running speeds: 9 speeds at 2 to 10 km/h each for male subjects: 8 speeds at 2 to 9 km/h each for female subjects. Energy expenditure measured with respiratory gas analysis was compared with that estimated by the calorie counter outfitted on the waist of the subjects. For running speed slower than 9 km/h, the work intensity reading on the calorie counter increased in direct proportion to the speed of the treadmill. The correlation between running speed and the work intensity reading of the calorie counter was linear up to 8 km/h (y = 0.95 x 0.2, r = 0.96, P less than 0.001). A linear relationship during treadmill exercise (at a speed of less than 9 km/h) was also established between energy consumption measured by respiratory gas analysis and that estimated from the calorie counter (y = 1.00 x + 11.7, r = 0.94, P less than 0.001). Thus, we validated the usefulness of the calorie counter for the assessment of energy expenditure during daily physical activities. PMID- 2333446 TI - [Quantitative evaluation of screening programs for chronic diseases]. AB - This paper addresses an epidemiologic approach to the quantitative evaluation of screening programs for chronic diseases. A new formula is advanced for the quantitative relationship between the yield of a screening program and the natural history of chronic disease, based on the two stage model of disease progression. The formula was applied to follow-up data of the participants and the proportions of cases detected by the screening were estimated as 15.3% for all diseases and 43.8% for hypertensive disorders. The formula is useful for continuous monitoring of ongoing screening programs as well as for potential impact evaluation of hypothetical programs. PMID- 2333447 TI - Multiple primary cancers in a case of chronic arsenic poisoning--an autopsy report. AB - This is an autopsy report of multiple primary cancers observed in a patient who had clinically been diagnosed as chronic arsenic poisoning. An 88-year-old man, non-smoker, had worked in an arsenic mine for 6 years from the age of 47. He had undergone operations for Bowen's disease and gastric cancer at ages 80 and 86, respectively. At autopsy, squamous cell carcinoma of the lung and a polypoid lesion in the piriform recess were found. Furthermore, microscopic examination revealed latent prostatic adenocarcinoma and oncocytoma in the kidney. The polypoid lesion of the piriform recess appeared to originate from the duct of the minor salivary gland in the pharynx, showing an adenoid cystic carcinoma-like pattern with squamous cell carcinoma in part. The cause of death was thought to be respiratory failure due to bronchopneumonia and pulmonary edema as well as hydrothorax, and chronic heart failure following ischemic heart disease. Bowen's disease was followed by four internal malignant tumors, even though the etiological relation between these cancers and arsenic is not clear. PMID- 2333448 TI - [Current findings in the physiopathology of hypertension in the elderly]. PMID- 2333449 TI - [Interruption of pregnancy in Switzerland 1982-1986]. AB - Official statistics available for the 5-year period considered in this paper reveal a general trend: decrease in the number of terminations, in absolute terms, both in women non-resident and in women resident in Switzerland. Amongst the latter, figures show a relative decrease in the 15 to 44-year age group and in relation to birth rate. Attitudes in 'liberal cantons' concerning termination of pregnancy are clearly justified. Efforts to ensure more widespread use of modern contraceptive methods must be continued (in conjunction with AIDS prevention). PMID- 2333450 TI - [The piriformis syndrome--a possible cause of sciatica]. AB - In a 50-year-old patient with unilateral pain in the buttocks and in the sciatica, a radicular compression syndrome was diagnosed. Because conservative therapy failed, surgical intervention for herniated disc was suggested. Clinical examination revealed a painfully contracted piriform muscle and irritation of the sciatic nerve. Through specific stretch exercises, quick recovery was effected. Based on this case report, typical clinical diagnoses and therapeutical possibilities for the piriformis syndrome are discussed. PMID- 2333451 TI - [Anemia, abnormal ECG, shock]. PMID- 2333452 TI - [Dr. Sklenar's Kombucha mushroom infusion--a biological cancer therapy. Documentation No. 18]. AB - Kombucha, a fungal infusion, is a 'symbiotic mixture' of bacteria, yeasts, tea and sugar. A number of components are listed, but exact analyses are not published. On the basis of 'thorough detoxification', Kombucha is claimed to be a prophylactic and therapeutic agent in countless diseases, such as rheumatism, intestinal disorders, ageing and cancer. All 'stages of the Sklenar blood picture' have to be treated with Kombucha Drink, Kombucha Drops, coli preparations and Gelum oral-rd for a period of months. A litre-bottle costs 13 DM, the blood analysis 150 Sfr. In the 1960's Dr. R. Sklenar developed a 'biological cancer therapy with Kombucha as the main agent' and his own system of diagnosing cancer. Sklenar's diagnosis of cancer is based on iris diagnosis and demonstration of the causative organism by means of a 'Blood picture according to Dr. Sklenar'. He claims, on one hand, that cancer is only one of the many metabolic diseases and, on the other, that viruses, in his view parasitic microorganisms in general, are responsible for the pathogenesis of cancer. No preclinical and nor investigations are available, as 'success has proved him (Dr. Sklenar) to be right'. The seven 'case histories' described have no solid medical data. There is so far no evidence to support the claim that Kombucha offers 'effective biological treatment of cancer'. PMID- 2333453 TI - [A case from practice (163). 1. Suspicion of a cystadenolymphoma of the right parotid area. 2. Status following subacute stenosis of the deep femoral artery and the tibio-fibular trunk on the right, 1980. 3.Shoulder-hand syndrome. 4. Nicotine abuse]. PMID- 2333454 TI - [Attempts to prevent intrauterine growth retardation using platelet anti aggregants]. AB - Intrauterine underdevelopment is a frequent complication in pregnancies associated with high blood pressure. It can also happen in the absence of this symptom but in a similar context. During these pregnancies, homeostasis problems were often shown to be at the root of placental abnormalities responsible for the development problems. This is why the authors of this article have tried to prevent intrauterine underdevelopment by prescribing antiplatelet drugs as from the start of the 2nd trimester of pregnancy. They compare their encouraging results with those of other teams and conclude that a larger prospective trial is necessary. PMID- 2333455 TI - [Management of gestational diabetes: objectives and results]. AB - Control of diabetes may easily, in gestational diabetes, avoid possible ketosis in the mother and fetal death. Reduction of fetal macrosomia is much less efficient. PMID- 2333456 TI - [The ideal time for delivery]. AB - The authors analyze the results of a three-year study of the variations of the degree of fetal distress according to the time of spontaneous delivery. The degree of fetal distress during labour is definitely high if the delivery takes place during the 42nd week. In primipara, where labour lasts more than 6 hours, this results in a level of cesarean sections due to fetal distress after 41 weeks which is significantly high (P less than 0.001) compared to the preceding three weeks. The authors conclude that, in terms of minimum fetal distress, the ideal delivery time would be before 41 full weeks of amenorrhea; as for the stagnation of the dilatation, the same observation is made. PMID- 2333457 TI - [Results of a policy of labor induction]. AB - In 1986 and 1987, among 1,323 patients who came in labour to the "Clinic Saint Anne", 672 (50.8 p. cent) were induced without any pathological reason as part of a labour protocol. The technique used consisted in the combination of oxytocics and rupture of the membranes. 85 p. cent received a peridural anesthesia. Comparison between scheduled deliveries and spontaneous labour inductions show no significant difference concerning terms and birth weights. The labour is longer by an average of one hour in the group of scheduled deliveries. In this group, the percentage of caesarean sections is 8.2 p. cent versus 9.12 p. cent (NS). No child born following a scheduled delivery required resuscitation and only one was transferred to pediatrics (because of infection). PMID- 2333458 TI - [Are unexpected pregnancy over age 40 at high risk?]. AB - A study concerning 5 years of activity at the Maternity of La Pitie, has shown differences in the population of pregnant women after the age of 40: decreased absolute number, relative increase of primiparous women, improvement of the socio economic level, resulting in a decreased maternal and fetal pathology. The perinatal mortality remains almost 3 times higher than for the overall population. PMID- 2333459 TI - [An evaluation method for the determination and monitoring of urinary HCG]. AB - A kit of anti-beta hCG monoclonal antibodies (Pharmacia beta hCG Riact) has been tested in the assay and monitoring of urinary hCG. After several tests, the technique was found to be reproducible and specific for assay of hCG and showed good sensitivity in urine assays. Optimal sensitivity was seen in the urine pH range 5.5 and 10.00. Below 5.5 and above 10.00, its detection capacity dropped off sharply. Dilution of urine with the kit buffer gave hormonal values comparable to those of undiluted urine, but improved them substantially when the urine pH was below 5.5. It is therefore wise to dilute urine to avoid the potential risk of assay interference by urine acidity. In frozen urine, hCG concentrations tend to decrease but are not altered significantly. This recently developed method allows easy and reliable monitoring of urinary hCG for detection of unknown pregnancy in spontaneous cycles, surveillance of the state of embryos transferred during in vitro fertilization cycles, and evaluation of the efficacy of treatment of tumors secreting (beta hCG). PMID- 2333460 TI - [Acute idiopathic dilatation of the right colon or Ogilvie's syndrome. Apropos of a case encountered after cesarean section]. AB - The syndrome of acute colectasia of the right colon following a caesarean section is a rare disease observed and described for the first time by Ogilvie in 1948. Many etiopathological hypotheses have been formulated but recent studies demonstrate the role of the neuro-vegetative nervous system, causing the functional obstacle responsible for the idiopathic right colon dilatation. The clinical picture of low obstruction is seldom typical, as in our case; however, the abdominal X-Ray easily confirms the diagnosis, since the caecal distention may exceed 10 cm in diameter. Most of the time, the prognosis is favorable after aspiration via colonoscopy; caecal perforation is always the spontaneous outcome, due to the "vicious cycle" perpetuating the functional obstruction. PMID- 2333461 TI - Liability insurance. PMID- 2333462 TI - Going green. PMID- 2333464 TI - Consumers of education. PMID- 2333463 TI - Working for a health environment. PMID- 2333465 TI - Purification and characterization of hamster serum amyloid A protein (SAA) by cholesteryl hemisuccinate affinity chromatography. AB - High-density lipoprotein (HDL) apolipoprotein was separated from hamster serum by cholesteryl hemisuccinate affinity chromatography (CHAC) in comparison with the density-gradient ultracentrifugation (DGUC). The apolipoprotein recovery from serum by CHAC was 70% and by DGUC 80%. This disadvantage is compensated for by the ease of purification by CHAC, a method particularly suited for the processing of large amounts of serum. From the acute-phase HDL CHAC fraction, apo SAA was isolated by gel filtration. Using isoelectrofocusing, two-dimensional gel electrophoresis, and titration curve, four isotypes of hamster apo SAA were identified and characterized. In the acute-phase serum, one of the isotypes was predominant (apo SAA1). In serum of amyloidotic animals, the relative contribution of apo SAA1 was considerably lower, suggesting selective removal of the latter during amyloidogenesis and possibly its deposition in hamster AA amyloid. Furthermore, the affinity chromatography method was modified with gradient elution of affinity-bound material. By this method HDL apolipoprotein was separated into three subclasses. Apo SAA was shown to associate with two different subclasses. In acute-phase serum most of the apo SAA1 was found in the subclass with the lowest affinity for the cholesteryl beads, whereas the latter was depressed in amyloidotic serum, suggesting that the amyloidogenicity of a particular apo SAA isotype is determined by its cholesteryl-binding properties. PMID- 2333466 TI - HLA heterozygosity in insulin-dependent diabetes is most frequent at the DQ locus. AB - Restriction fragment length polymorphism using an HLA-DQ beta-chain genomic probe showed that 63 children with insulin-dependent (type 1) diabetes mellitus (IDDM) were all (100%) positive for the BamH1 fragments 12 kb and/or 4 kb compared to 98% (62/63) for HLA-DR3 and/or 4 and 75% (47/63) for HLA-B8 and/or 15. The 36 (56%) DR3-positive children were all 4-kb-positive; however, a total of 44 (70%) children were 4-kb-positive (P less than 0.02). The 55 (87%) DR4-positive children were all 12-kb-positive, but a total of 56 (89%) were 12-kb-positive (NS). The heterozygosity at the HLA region increased from 11/63 (18%) for HLA B8/15 to 29/63 (46%) for HLA-DR3/4 (P less than 0.0004) and to 37/63 (59%) for the HLA-DQ 4 kb/12 kb fragments (P less than 0.02). The test of an equal probability of a positive result under the adjacent pair of tests indicates that the increased risk of developing IDDM in association with HLA-DQ is to a great extent due to heterozygosity at this locus. There were no differences between the 4 kb/12 kb and the DR3/4-positive IDDM children with respect to fasting or meal stimulated C peptide, insulin requirement, or levels of insulin antibodies formed during the first 12 months of insulin therapy. Our results support the hypothesis that HLA-DQ is closely associated with an increased risk of childhood IDDM, and when typed for at this locus parameters of the clinical course were homogeneous, suggesting that factors other than HLA-DQ may determine previously observed differences between IDDM children in clinical or functional parameters. PMID- 2333467 TI - Secretory component-binding properties of normal serum IgM. AB - Our aim was to investigate why serum IgM is poorly transferred into secretions in normal subjects. Indeed, the low IgM level in secretions contrasts with the capacity of monoclonal IgM to bind to secretory component (SC), but it is not well established to what extent normal serum IgM can do so. The mean SC affinity was studied with a polyclonal IgM preparation from 250 normal subjects and with a representative pool of 100 different monoclonal IgM. The SC-binding percentages varied as a function of the IgM/SC molar ratio according to a common hyperbolic curve, with similar association constants: Ka = 4.19 +/- 2.61 x 10(7) M-1 (polyclonal pool) and Ka = 5.80 +/- 2.73 x 10(7) (monoclonal pool). It thus appears that the large difference in IgM concentrations between blood and secretions cannot be due to an SC-binding defect of serum IgM, but is probably explained by its low diffusion from blood to the extravascular compartment. PMID- 2333468 TI - Whole cholera toxin and B subunit act synergistically as an adjuvant for the mucosal immune response of mice to keyhole limpet haemocyanin. AB - Cholera toxin (CT) is a potent stimulator of IgA responses when administered orally and has been shown to promote IgA responses to a second protein such as keyhole limpet haemocyanin (KLH) if this is fed simultaneously. In this paper we show that whilst feeding 5 mg KLH with either 0.5 micrograms CT or 10 micrograms B subunit fails to stimulate a mucosal IgA response to KLH, feeding 0.5 microgram CT and 10 micrograms B subunit together with 5 mg KLH produces a local IgA anti KLH response as great as that produced by 10 micrograms of whole CT. In addition to stimulating IgA responses in the lamina propria, preliminary results indicate that cellular responses are also stimulated, as we have demonstrated KLH antigen driven proliferation of cells isolated from groups of mice fed either 10 micrograms CT + 5 mg KLH or 0.5 micrograms CT + 10 micrograms CTB + 5 mg KLH but not mice fed KLH alone or with either 10 micrograms CTB or 0.5 micrograms CT. These results indicate that the mucosal adjuvant action of CT is due to a synergistic effect involving both the GM1 binding of the B subunit and adenylate cyclase activation by the A subunit. PMID- 2333469 TI - A new surface antigen on human lymphocytes defined by the murine monoclonal antibody IVF7. AB - The murine monoclonal antibody (MoAb) IVF7 was produced against tumour cells from a patient with a CD3+, CD4+, CD8- T-cell chronic lymphatic leukaemia (T-CLL). The MoAb IVF7 showed reactivity with subpopulations of normal peripheral blood lymphocytes (PBL), as well as with a few cell lines of haematopoietic origin. Thirty-six per cent of PBL were stained with IVF7. Analysing subpopulations, we found that 80% of NK cells, 25% of T cells, and 10-20% of B cells were positive. The myelomonocytic cell line KG-1 was also stained. The molecular weight of the molecule was 40 kDa under reducing conditions. The antigen was found to be trypsin-sensitive. MoAb IVF7 could modulate the antigen from the cell surface. The antibody did not stimulate PBL to DNA synthesis, nor did it significantly influence NK cell-mediated killing. PMID- 2333470 TI - Cellular fibronectin in rheumatoid synovium and synovial fluid: a possible factor contributing to lymphocytic infiltration. AB - Mouse monoclonal antibodies against ED sequence-containing cellular fibronectin (cFn) were used to show that Fn in the inflamed synovium is distinct from the major form of plasma Fn (pFn). An accumulation of cFn was seen at sites of hyperplasia of the rheumatoid synovial membrane and in the walls of small vessels in the synovium by immunofluorescence microscopy. cFn was also found in rheumatoid synovial fluid by immunoblotting. Approximately one-fifth of the T lymphocytes from rheumatoid synovial fluid bound to Fn. The binding of synovial fluid T cells was always higher than that from peripheral blood. These results have two implications. On the one hand, the cellular type of Fn may be an indicator of synovial inflammation. On the other hand, the deposition of Fn may be a factor contributing to the infiltration of mononuclear cells into the synovium. PMID- 2333471 TI - The seasonality of schizophrenic births: a reply to Marc S. Lewis. AB - Lewis contends that the previously demonstrated finding of seasonality of schizophrenic births is a statistical artifact due to the age-incidence effect. If Lewis is correct, then (1) January should have the highest schizophrenic birthrate, (2) December should have the lowest schizophrenic birthrate, (3) the Southern Hemisphere should show the same pattern as the Northern Hemisphere, and (4) the age-incidence effect should be more marked in younger age cohorts. None of these findings have been borne out by studies to date. It is concluded that the seasonality of schizophrenic birthrates is a replicable finding, and should be considered one of the more intriguing clues to the etiology of this disease. PMID- 2333472 TI - Does age incidence explain all season-of-birth effects in the literature? AB - Lewis (1989) has suggested that the effect of so-called age incidence on season of-birth data may be a sufficient explanation of the anomalies found in many samples of schizophrenic patients. Various predictions made by Lewis do not agree, however, with data available from some of the sources he quoted. Age incidence can be a source of error when a small age difference has a considerable effect on the likelihood of being included in a sample. Depending on methods of ascertainment, this is unusual in empirical studies. PMID- 2333473 TI - Age-incidence artifacts do not account for the season-of-birth effect in schizophrenia. AB - Contrary to the position taken by Lewis (1989), several articles have demonstrated an association between season of birth and the risk of schizophrenia after controlling for the age-incidence effect. The method used by Pulver et al. (1983) was misinterpreted by Lewis. Clarification of this method is provided along with additional references related to the season-of-birth issue. PMID- 2333474 TI - Diagnosis and screening for psychotic disorders in a study of the homeless. AB - In a survey of homeless men, the authors found that screening scales for psychotic symptoms (Psychiatric Epidemiology Research Instrument) and signs (6 item scale of observational ratings) predicted a rating of psychosis (possible, probable, or definite) on a diagnostic interview (Structured Clinical Interview for DSM-III-R: Psychotic Disorders) reasonably well, in a sample where psychosis was common. Although the two scales performed well when used in conjunction, neither scale showed adequate predictive power when used alone. The authors conclude that screening for psychotic disorders in community studies is feasible for some purposes. They suggest approaches to the use of diagnostic interviews and screening scales in future community studies that might enhance the interpretability as results as well as the efficacy of screening. PMID- 2333475 TI - Cognitive deficits and thought disorder: II. An 8-month followup study. AB - Schizophrenic (n = 21) and manic (n = 19) patients were followed up an average of 8 months after an index assessment during an acute admission. These patients were tested at both assessments with laboratory tasks measuring distractibility and reality monitoring and were examined with clinical ratings of positive and negative thought disorder. For manic patients, none of the measures predicted the patients' clinical state of followup, while negative thought disorder, although rare, was temporally stable. For the schizophrenic patients, both negative thought disorder and distractibility were temporally stable, and more severe negative thought disorder was found at index assessment in patients who were psychotic at followup. The differential utility of laboratory and clinical indices for the prediction of overall clinical state is related to these data. PMID- 2333476 TI - Hospitalization and the composition of mental patients' social networks. AB - Social networks of 310 chronically mentally ill patients in Chicago-area State mental hospitals were examined to assess the relationship between the number of hospitalizations and network size and composition. As the number and length of admissions increases, although network size remains stable, there are fewer relatives and friends in the network. The networks of patients with frequent admissions are composed primarily of people met through the mental health system and those known for a short time. These differences are neither related to diagnosis nor to severity of mental illness. The results suggest that the process of hospitalization is related to patients' sources of social support. Implications for readmissions are discussed. PMID- 2333477 TI - First person account: birds of a psychic feather. PMID- 2333478 TI - Substance abuse comorbidity in schizophrenia. PMID- 2333479 TI - Substance abuse comorbidity in schizophrenia: editors' introduction. AB - Substance abuse is a pervasive problem in American society that extends to persons with mental illness. Despite the fact that substance abuse in the mentally ill is a major clinical problem, there have been very few systematic investigations of the dimensions, nature, and treatment of this problem. This issue of the Schizophrenia Bulletin attempts to examine the problem of substance abuse in schizophrenia from various perspectives by reviewing the published literature, presenting original data, and identifying areas and approaches for future scientific investigation. PMID- 2333480 TI - Prevalence of substance abuse in schizophrenia: demographic and clinical correlates. AB - Methodological issues involved in assessing the prevalence of substance abuse in schizophrenia are discussed, and previous research in this area is comprehensively reviewed. Many studies suffer from methodological shortcomings, including the lack of diagnostic rigor, adequate sample sizes, and simultaneous assessment of different types of substance abuse (e.g., stimulants, sedatives). In general, the evidence suggests that the prevalence of substance abuse in schizophrenia is comparable to that in the general population, with the possible exceptions of stimulant and hallucinogen abuse, which may be greater in patients with schizophrenia. Data are presented on the association of substance abuse with demographics, diagnosis, history of illness, and symptoms in 149 recently hospitalized DSM-III-R schizophrenic, schizophreniform, and schizoaffective disorder patients. Demographic characteristics were strong predictors of substance abuse, with gender, age, race, and socioeconomic status being most important. Stimulant abusers tended to have their first hospitalization at an earlier age and were more often diagnosed as having schizophrenia, but did not differ in their symptoms from nonabusers. A history of cannabis abuse was related to fewer symptoms and previous hospitalizations, suggesting that more socially competent patients were prone to cannabis use. The findings show that environmental factors may be important determinants of substance abuse among schizophrenic-spectrum patients and that clinical differences related to abuse vary with different types of drugs. PMID- 2333481 TI - Schizophrenic birth seasonality and the age-incidence artifact. AB - Lewis (1989) dismisses a large number of articles in which schizophrenic winter birthrate excesses have been reported as the result of either design problems or the age-incidence artifact. We review about 20 studies in which the effects of age incidence have been controlled in one way or another. The majority support the conclusion that the seasonality effect is due neither to artifact nor deficient research design. We also correct two significant errors in Lewis' description of our prior work. PMID- 2333482 TI - Diagnosis of alcohol use disorders in schizophrenia. AB - Alcohol use disorders are common comorbid conditions in schizophrenia, and their presence is associated with poor adjustment and poor treatment response. Standard alcohol assessment instruments have not been validated for use with schizophrenic patients, and several authors have questioned the validity of these patients' self-reports. A reliable and valid screening procedure for assessing alcohol use is needed. The present study used the following three methods to evaluate a rural sample of 75 outpatients with DSM-III-R schizophrenia or schizoaffective disorder: (1) clinical records; (2) research interviews using standard alcohol assessment instruments; and (3) case managers' ratings. In addition, consensus diagnoses, determined by combining information from all three methods with intensive case reviews, were used to determine the sensitivity and specificity of the other approaches. As expected, clinical evaluations frequently missed alcohol problems. Research interviews and case managers' ratings differentiated between alcoholic and nonalcoholic schizophrenic patients and were highly correlated. Case managers' ratings, which incorporated longitudinal observations of behavior and collateral reports as well as interview data, were more sensitive measures of current alcohol use disorders than research interviews. Subjects frequently manifested alcohol-related problems that interfered with community adjustment without the full dependence syndrome, suggesting that schizophrenic patients may be particularly vulnerable to negative effects of alcohol. PMID- 2333483 TI - The effect of prompting and reinforcement of activity in elderly demented inpatients. AB - On a ward for 24 psychogeriatric patients, 18 were randomly assigned to three groups with different experimental conditions. The first group was prompted and reinforced for different activities; the second was only prompted; and the third served as a control group. Activities, both the trained ones and others, were continuously monitored throughout the five week study. The results showed a clear increase in the trained activities after training. The prompting condition was effective, and the addition of reinforcement did not add any to the effects. There was no generalization to untrained activities, and the effects did not last at the 1 hr or 21 hr assessments, but was clearly visible at 5 min after training. Time seemed to be more important than place, i.e. the effect ceased with elapsed time, not because of changes in the situation. PMID- 2333484 TI - Reliability of drug use responses in a longitudinal study. AB - In a prospective longitudinal study of adolescents' drug use, the trustfulness of the self-reports about drug use was investigated by means of a test for logical consistency. A sample of 1936 high school students completed a written survey in the fall of 1987 and again in spring 1988, seven to eight months later. The findings indicate that the information obtained is logically consistent at one particular point in time. Analyses show, however, that the consistency drops somewhat over time. The legal drug use responses show the highest consistency, the answers regarding hard drugs like amphetamine and heroin show the least favourable consistency, with cannabis and inhalants somewhere in the middle. There seem to be two main reasons for the inconsistent answers: some respondents wilfully underreport their drug consumption. This seems partly to be a function of the level of illegality of the drug. However, poor memory and episodic uses of such drugs seem also to be important. Generally this study agrees with other studies and indicates an overall relatively high level of longitudinal consistency regarding drug use responses. This kind of survey must therefore be regarded as a relatively reliable instrument in collecting information regarding drug use. PMID- 2333485 TI - Familial similarity in Type A behaviour and physiological measurements as related to sex. AB - Thirty-one families with pre-school children were examined with regard to Type A behaviour and cardiovascular and neuroendocrine measurements. Type A scores (MYTH) of the children from the ages of three to six were positively correlated with independent Type A measurements (Jenkins Activity Survey, Bortner Type A scale) of the parents (significant for fathers but not for mothers). The children's resting systolic blood pressures were significantly correlated with maternal and paternal values, while no significant familial aggregation was found for diastolic blood pressure, heart rate, catecholamine or cortisol excretion. The children's systolic and diastolic blood pressures and adrenaline excretion were significantly correlated between ages three and six. The results are consistent with the assumption that genetic as well as environmental factors contribute to the development of Type A behaviour. No significant association was found between Type A scores and physiological measurements during routine activities in the children or the adults. PMID- 2333486 TI - Fear questionnaires for simple phobias: psychometric evaluations of a Norwegian sample. AB - The present study presents psychometric data for four different phobic fear questionnaires in a Norwegian sample of 284 subjects. The questionnaires concerned fear of flying, snakes, spiders and a questionnaire of general phobic complaints. The results showed a high estimate of internal consistency, and a very high test-retest reliability for all questionnaires. A low to moderate degree of intercorrelation between the questionnaires appeared. A clear sex difference emerged in responding to all four questionnaires. In addition, a clinical sample of phobics with fear of flying as the main symptom was compared to the larger sample on a fear of flying scale. The results showed a clear difference in responding between the samples. The present study concludes that the four different fear questionnaires yielded a high degree of reliability, and their use in clinical practice is encouraged. PMID- 2333487 TI - Normal values for Type A behaviour patterns in Danish men and women and in potential high-risk groups. AB - The Jenkins Activity Survey (JAS) was administered to a normal population of randomly selected Danish adults, to patients consulting a cardiologist, and to physicians in order to compare those groups in terms of their coronary-prone (Type A) behaviour patterns. The standard procedure of rating the JAS was used in order to obtain scores for each of the four subscales: Type A (time urgency and ambitiousness), Factor S (speed and impatience) Factor H (hard-driving and competitive) and Factor J (job involvement). Gender differences were observed in the normal population for each of the four subscale scores, and age-related differences were obtained for Factor J. Elevated scores for Factor S were obtained by physicians and by people in the population who had a cardiovascular disorder. Physicians had also elevated scores for Factor J, whereas their Factor H scores tended to be reduced. No reliable differences in JAS subscale scores were observed between four groups of heart patients (i.e. angina pectoris, arterial hypertension, atrial fibrillation and atherosclerosis), although there was a tendency for Factor J to be elevated in atherosclerosis. The findings provide normal values for JAS scores in Danish men and women, and suggest that some facets of coronary-prone behaviour may be enhanced in Danish high-risk groups. PMID- 2333488 TI - Facial reactions to fear-relevant stimuli for subjects high and low in specific fear. AB - This study was performed to investigate whether subjects high and low in fear of snakes react with different facial electromyographic (EMG) responses when exposed to snakes. Two groups of subjects were exposed to slides of snakes or flowers. After the experiment they rated their fear of snakes on a questionnaire and based on these ratings they were divided into high and low fear groups. Facial EMG was measured from the corrugator and zygomatic muscle regions. As predicted the high fear group reacted with a facial response interpretable as a negative emotional reaction whereas the low fear group did not. This difference was specific to snakes because high and low groups did not differ in responses to slides of flowers. The results are consistent with the proposition that facial EMG technique is a sensitive tool to distinguish reactions between subjects high and low in specific fears. PMID- 2333489 TI - Perceived unpleasantness and facial reactions to auditory stimuli. AB - This study examined whether facial electromyographic (EMG) reactions differentiate between identical tone stimuli which subjects perceive as differently unpleasant. Subjects were repeatedly exposed to a 1000 Hz 75 dB tone stimulus while their facial EMG from the corrugator and zygomatic muscle regions were measured. Skin conductance and heart rate responses were also measured. The subjects rated the unpleasantness of the stimulus and based on these ratings they were divided into two groups, High and Low in perceived unpleasantness. As predicted the facial EMG activity reflected the perceived unpleasantness. That is, the High group but not the Low group reacted with an increased corrugator response. The autonomic data, on the other hand, did not differ between groups. The results are consistent with the proposition that the facial muscles function as a readout system for emotional reactions and that facial muscle activity is intimately related to the experiential level of the emotional response system. PMID- 2333490 TI - Action and emotion in everyday life. AB - This study of naturally occurring behaviour employed a "beeper technique" to investigate the actions carried out by 152 subjects in eight different groups, viz. adult students, employed students who were also parents, unemployed, art students, doctoral students, alcoholics, retired people and a control group. Actions were sampled for seven subsequent days, five times per day between 8 a.m. and 10 p.m. at randomly selected occasions. Each action was rated on a number of variables, shortly after it was sampled (median delay approximately 10 min). Some of the findings were: Time allocation corresponded well with national estimates. Being under situational control was highly aversive. Instrumental and consummatory orientations correlated positively. The background variables were, on the whole, only rather weakly related to action ratings, but it was found that women and retired persons tended to report a higher level of well-being. PMID- 2333492 TI - Tainted feed, mad cows. Could a British cattle disease infect U.S. herds? PMID- 2333491 TI - High fertility in sub-Saharan Africa. PMID- 2333493 TI - Through a glass, darkly. Are wearers of tinted glasses more likely to be depressed? PMID- 2333494 TI - An antidrug message gets its facts wrong. PMID- 2333495 TI - Radiation risks revisited. A study raises the specter of an effect on offspring. PMID- 2333496 TI - Adoptive immunotherapy for cancer. PMID- 2333497 TI - Trick of the tongue. A unique mechanism of taste means no substitute for salt. PMID- 2333498 TI - Cancer catcher. Neural net catches errors that slip through Pap tests. PMID- 2333499 TI - Wiring the campuses. PMID- 2333500 TI - The value of animal research. PMID- 2333501 TI - Federal housing and poverty. PMID- 2333502 TI - NSF: hard times amid plenty. PMID- 2333504 TI - NIH director: the final lap? PMID- 2333505 TI - Top focus needed for AIDS effort. PMID- 2333503 TI - Biotech companies lobby for Federal regulation. PMID- 2333506 TI - An animal genome project? PMID- 2333507 TI - China: a living lab for epidemiology. PMID- 2333508 TI - Tapping into nerve conversations. PMID- 2333509 TI - Risk within reason. AB - Advances in low-level risk detection threaten to engulf us with information. Regulators typically respond to each newly highlighted risk, whether painstakingly uncovered through scientific investigation or divulged with fanfare by the media, on an ad hoc basis. This response makes it hard to relate disparate risks to the overall risk level and impedes intelligent risk reduction, which must consider the costs and benefits involved. Efficient risk management requires decisions not only about what to regulate and how stringently, but also about the appropriate division of labor among the agents influencing risks. These agents include individuals, whose potential contributions too often are overlooked, corporations, and government. PMID- 2333510 TI - Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa. AB - A low molecular weight serine protease inhibitor (TAP) was purified from extracts of the soft tick, Ornithodoros moubata. The peptide is a slow, tight-binding inhibitor, specific for factor Xa (Ki = 0.588 +/- 0.054 nM). The inhibitor also acts as an anticoagulant in several human plasma clotting assays in vitro. Its amino acid sequence (60 residues) has limited homology to the Kunitz-type inhibitors. However, unlike other inhibitors of this class, TAP inhibits only factor Xa. It had no effect at a 300-fold molar excess on factor VIIa, kallikrein, trypsin, chymotrypsin, thrombin, urokinase, plasmin, tissue plasminogen activator, elastase, or Staphylococcus aureus V8 protease. TAP's specificity and size suggest that it may have therapeutic value as an anticoagulant. PMID- 2333511 TI - K+ current diversity is produced by an extended gene family conserved in Drosophila and mouse. AB - The Drosophila Shaker gene on the X chromosome has three sister genes, Shal, Shab, and Shaw, which map to the second and third chromosomes. This extended gene family encodes voltage-gated potassium channels with widely varying kinetics (rate of macroscopic current activation and inactivation) and voltage sensitivity of steady-state inactivation. The differences in the currents of the various gene products are greater than the differences produced by alternative splicing of the Shaker gene. In Drosophila, the transient (A current) subtype of the potassium channel (Shaker and Shal) and the delayed-rectifier subtype (Shab and Shaw) are encoded by homologous genes, and there is more than one gene for each subtype of channel. Homologs of Shaker, Shal, Shab, and Shaw are present in mammals; each Drosophila potassium-channel gene may be represented as a multigene subfamily in mammals. PMID- 2333512 TI - Effect of phospholipase C-gamma overexpression on PDGF-induced second messengers and mitogenesis. AB - Platelet-derived growth factor (PDGF) stimulates phospholipase C (PLC) activity and the phosphorylation of the gamma isozyme of PLC (PLC-gamma) in vitro and in living cells. The role of PLC-gamma in the phosphoinositide signaling pathway was addressed by examining the effect of overexpression of PLC-gamma on cellular responses to PDGF. Overexpression of PLC-gamma correlated with PDGF-induced tyrosine phosphorylation of PLC-gamma and with PDGF-induced breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2). However, neither bradykinin- nor lysophosphatidic acid-induced phosphoinositide metabolism was enhanced in the transfected cells, suggesting that the G protein-coupled phosphoinositide responses to these ligands are mediated by other PLC isozymes. The enhanced PDGF induced generation of inositol trisphosphate (IP3) did not enhance intracellular calcium signaling or influence PDGF-induced DNA synthesis. Thus, enzymes other than PLC-gamma may limit PDGF-induced calcium signaling and DNA synthesis. Alternatively, PDGF-induced calcium signaling and DNA synthesis may use biochemical pathways other than phosphoinositide metabolism for signal transduction. PMID- 2333513 TI - Health care rationing. PMID- 2333515 TI - Struggling to do science for society. PMID- 2333514 TI - Competition exclusion principle. PMID- 2333516 TI - Learning to drink from a fire hose. PMID- 2333517 TI - Dingell: AIDS researcher in conflict. PMID- 2333518 TI - Billion-dollar orphans: prescription for trouble. PMID- 2333519 TI - Mycoplasmas in the AIDS spotlight. PMID- 2333520 TI - "Superantigens" may shed light on immune puzzle. PMID- 2333521 TI - Crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 A. AB - The three-dimensional structures of an antibody to a peptide and its complex with the peptide antigen have been determined at 2.8 A resolution. The antigen is a synthetic 19-amino acid peptide homolog of the C helix of myohemerythrin (Mhr). The unliganded Fab' crystals are orthorhombic with two molecules per asymmetric unit, whereas the complex crystals are hexagonal with one molecule per asymmetric unit. The Fab' and the Fab'-peptide complex structures have been solved independently by molecular replacement methods and have crystallographic R factors of 0.197 and 0.215, respectively, with no water molecules included. The amino-terminal portion of the peptide sequence (NH2-Glu-Val-Val-Pro-His-Lys-Lys) is clearly interpretable in the electron density map of the Fab'-peptide complex and adopts a well-defined type II beta-turn in the concave antigen binding pocket. This same peptide amino acid sequence in native Mhr is alpha-helical. The peptide conformation when bound to the Fab' is inconsistent with binding of the Fab' to native Mhr, and suggests that binding of the Fab' to conformationally altered forms of the native Mhr or to apo-Mhr. Immunological mapping previously identified this sequence as the peptide epitope, and its fine specificity correlates well with the structural analysis. The binding pocket includes a large percentage of hydrophobic residues. The buried surfaces of the peptide and the antibody are complementary in shape and cover 460 A2 and 540 A2, respectively. These two structures now enable a comparison of a specific monoclonal Fab' both in its free and antigen complexed state. While no major changes in the antibody were observed when peptide was bound, there were some small but significant side chain and main chain rearrangements. PMID- 2333522 TI - A genetic test of the natal homing versus social facilitation models for green turtle migration. AB - Female green turtles exhibit strong nest-site fidelity as adults, but whether the nesting beach is the natal site is not known. Under the natal homing hypothesis, females return to their natal beach to nest, whereas under the social facilitation model, virgin females follow experienced breeders to nesting beaches and after a "favorable" nesting experience, fix on that site for future nestings. Differences shown in mitochondrial DNA genotype frequency among green turtle colonies in the Caribbean Sea and Atlantic Ocean are consistent with natal homing expectations and indicate that social facilitation to nonnatal sites is rare. PMID- 2333523 TI - Advances in ifosfamide chemotherapy. Proceedings of a symposium. November 4-5, 1989, Key Biscayne, FL. PMID- 2333524 TI - Ifosfamide combinations in lymphoma. AB - From 1977 to 1989, combination ifosfamide and etoposide has been used at the M.D. Anderson Cancer Center for management of lymphoma in both untreated patients and patients with recurrent disease. Results of the various salvage regimens are reviewed. On the average, overall and complete response rates have been 60% and 25%, respectively. Median survival time was 9 months for relapsed intermediate grade lymphoma and 12 months for low-grade lymphoma. The preliminary results of a new combination, mesna, ifosfamide, novantrone, etoposide (MINE), are discussed. Finally, we discuss the long-term results (at 10 years of follow-up) of a front line protocol using ifosfamide/methotrexate/etoposide (IMVP-16) as consolidation or intensification for cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) responders. At 10 years, 62% of intermediate-grade lymphoma patients are alive and disease free. PMID- 2333525 TI - Advances in hypercalcemia of malignancy. PMID- 2333526 TI - [Shock in the surgical patient]. PMID- 2333528 TI - [The encyclical Sollicitudo Rei Socialis and the world of health]. PMID- 2333527 TI - [Cerebrovascular strokes]. PMID- 2333529 TI - [Pediatric infection with the human immunodeficiency virus]. PMID- 2333530 TI - [Contraceptives. A look to the future]. PMID- 2333531 TI - [Self-help groups in the rehabilitation of alcoholism and other drug dependencies]. PMID- 2333532 TI - [Childhood asthma]. PMID- 2333533 TI - [The cereals. A dietetic menu]. PMID- 2333534 TI - [Rehabilitation nursing care of the patient with a cerebrovascular stroke and hemiplegic incapacity]. PMID- 2333535 TI - Uplifting the abstract. PMID- 2333536 TI - Traumatic posterior dislocation of the hip. PMID- 2333537 TI - Methylprednisolone in systemic lupus erythematosus. AB - 39 patients who received pulse methylprednisolone for disease manifestations of systemic lupus erythematosus were studied for zero to twenty-four weeks following therapy. Pulse methylprednisolone was given as intravenous infusions of methylprednisolone (10 mg/kg body weight) over one hour each day for three consecutive days. 27 (69.2%) patients were treated for lupus nephritis, 12 (30.8%) patients for non-renal manifestations of lupus. 17 (63.0%) of the renal lupus patients and 7 (58.3%) of the non-renal lupus patients showed clinical response. 11 (28.2%) patients had infections from which 7 (63.6%) died. Overall, 15 (38.5%) patients died. Early deaths (occurring within the first two weeks) were mainly due to disease activity while later deaths were mainly due to infection. In conclusion, the majority of lupus patients appeared to have had a beneficial response to pulse methylprednisolone therapy. PMID- 2333538 TI - Ophthalmic screening for diabetics: the importance of physician-ophthalmologist collaboration in the prevention of blindness. AB - Diabetes mellitus as a disease is a dragon with many heads. To cope with it, each manifestation must be deftly handled by family physician and specialists in unison. Similarly, the spectre of diabetic retinopathy is best exorcised before it manifests - by effective prophylactic screening. This programme can only be successful through a co-ordinated effort of both physicians and ophthalmologists. In this paper, we present one such agenda which we have adopted, The result indicate that a fifth of diabetics have retinopathy, and that sight threatening disease affects 7% of those screened. More critically, it also establishes that a cost-effective method of screening can be achieved through a synergetic endeavour of primary care physician and specialist. PMID- 2333539 TI - Shoulder dystocia-a review at the Department of Obstetrics and Gynaecology, Alexandra Hospital, Singapore. AB - Shoulder dystocia is associated with a high incidence of perinatal morbidity, mortality and maternal morbidity. The present study was undertaken to review all the cases of shoulder dystocia at the Department of Obstetrics and Gynaecology, Alexandra Hospital during a 11-year period from January 1978 until December 1988. The incidence of shoulder dystocia in this series was 1:1739 deliveries or 0.05%. The constant awareness of the possibility of rapid development of shoulder dystocia with its potentially dangerous consequences should always be kept in mind. Shoulder dystocia drills should be held regularly in the resident training programme. PMID- 2333540 TI - Efficacy of health education programme on awareness of AIDS among transsexuals. AB - A study of the awareness of Acquired Immunodeficiency Syndrome (AIDS) among Transsexual prostitutes attending the Middle Road Hospital was made. The present study involved 71 subjects of a cohort of 100 who were interviewed a year earlier and had subsequently been given intensive health education. The results show that there was now an increased awareness of AIDS in virtually all the subjects studied. In contrast, there has been no significant change in the use of safe sex practices as a direct consequence of this knowledge. The reasons for this are discussed. There may be a need for more intensive behaviour modification programme in this group of individuals. PMID- 2333541 TI - Oculocardiac reflex in strabismus surgery under general anaesthesia--a study of Singapore patients. AB - A study of 80 patients with strabismus undergoing correctional surgery under general anaesthesia was done. A comparison was made with regards to the incidence of oculocardiac reflex between patients premedicated with intramuscular atropine 0.015 mg/kg and non-premedicated patients. We found that premedication with atropine reduces the incidence and the morbidity of the oculocardiac reflex. PMID- 2333542 TI - Psychiatric referral pattern in a general hospital. AB - Between September 1986 and January 1988, a sixteen-month period, a total of 494 inpatients in Tan Tock Seng Hospital were referred for psychiatric opinion. 181 were referred for suicidal tendency and 313 for other reasons. An analysis of these two groups of referrals was done to study any change in referral trends. The findings show that while the basic diagnostic categories of patients do not differ drastically from an earlier study in Singapore General Hospital by Tsoi and Kok, Tan Tock Seng Hospital had its own pattern of requirements for psychiatric consultation because of its own unique patient characteristics. PMID- 2333544 TI - Brain metastasis of unknown origin. AB - From 1973 to 1984, 119 patients presented to the Department of Neurosurgery, Royal Victoria Hospital, Belfast, with brain metastases, the primary sites of which remained unknown in 33 cases one month after discharge. About half of these cases were solitary and neurological lateralising signs were the commonest presentation. Of those cases in which surgery was performed, the majority remained improved one month after surgery. The one month mortality rate was only 3%. This study shows that with aggressive and appropriate treatment including surgical excision or decompression in solitary cases, an improved quality of life in the immediate postoperative period can be achieved in this particular group of brain metastases. A small number of patients remained alive and well after 6 months. PMID- 2333543 TI - Minimal change glomerulopathy in two patients after thymectomy. AB - Two myasthenia gravis patients developed nephrotic syndrome due to minimal change glomerulopathy 3 to 14 years after thymectomy for malignant thymoma. Impaired cellular and humoral immunity has been documented in patients with thymoma and persists after thymectomy. The occurrence of minimal change disease lends support to the hypothesis that the glomerulopathy is secondary to T-cell dysfunction, resulting in production of a lymphokine which increases glomerular basement membrane permeability. PMID- 2333545 TI - Fibrinogen level in health and disease. AB - The plasma fibrinogen concentration of 47 healthy individuals was measured in order to determine the reference range for our laboratory, which was calculated to be 1.75-3.31 g/l. The plasma fibrinogen concentration of 44 hospital patients was also measured for comparison. These patients were selected because they were free from bleeding tendency and liver disease. The distribution of their fibrinogen levels was Gaussian, but more wide-based than the distribution of our normal controls. The mean fibrinogen value of the patient group was 3.60 g/l, significantly higher than that of the healthy group, which was 2.53 g/l. The reasons why the fibrinogen distribution graph of patients assumed such a pattern and the role of fibrinogen in health and disease are discussed. PMID- 2333546 TI - Surgical treatment of congenital choledochal cyst. AB - 20 cases of congenital choledochal cyst were operated by modified Lilly's method from 1980 to November 1985 in our Hospital. There were 4 males and 16 females. Their ages ranged from 50 days to 15 years with a mean of 5.1 years. All patients had preoperative ultrasonographic examination, barium meal radiography of the gastrointestinal tract or percutaneous transhepatic cholangiography. All had choledochal cystectomy with retention of the outer layer of the posterior wall of the cyst. We modified Lilly's method by injecting normal saline between the outer and inner layer of the choledochal cyst so that the outer layer could be isolated. Reconstruction of the biliary tract was then performed. 2 patients had choledochoduodenostomy and 18 patients had hepaticojejunostomy (1 end to end and 17 end to side). 19 patients had also had cholecystectomy. The post-operative course of the operation was found to be smooth and safe. Patients were followed up for a period from 6 months to 7 years. 3 patients had cirrhosis of liver, 2 of whom died within 8 months. The mortality rate in our series was 10%. The operative treatment and the problems of biliary reconstruction are discussed. PMID- 2333547 TI - A study of cleft lip and palate in neonates born in a large Malaysian maternity hospital over a 2-year period. AB - Out of 52,379 babies delivered in the Maternity Hospital, Kuala Lumpur, over a 2 year period, 64 were born with cleft lip and/or palates. The rate of occurrence of cleft was 1.24 per 1000 livebirths or 1.20 per 1000 deliveries. The Chinese babies had the highest incidence (1.9 per 1000 deliveries) while the Malays had the lowest (0.98 per 1000 deliveries). The most common type was unilateral cleft of the primary and secondary palates. Among the Indian babies, cleft of the secondary palate was most common. 18.8 percent of all the affected babies had positive family history of cleft. 10.9% of the mothers of affected babies had positive history of drug ingestion especially Chinese herbs during pregnancy. Associated congenital abnormalities occurred in 15.6% of the babies with cleft lip and/or palate. PMID- 2333548 TI - Asthma in Singapore children. AB - Over the last decade, admissions from respiratory infections have declined but there had been an increase in admissions from Bronchial Asthma in Singapore Government Hospitals. Better recognition by doctors and increased prevalence are important factors. However, mortality had remained low. Like other mortality studies, underestimation of the severity of asthma and undertreatment are the major contributing factors to asthma deaths in Singapore children. Therefore, better public education and continuing education of medical personnel may help to reduce deaths from asthma in children and adolescents. PMID- 2333549 TI - Medico-legal and ethical issues in neonatology. AB - Very small and sick neonates are being saved with modern technology. However, the cost is high. Obstetricians and neonatologists are often faced with the difficult task of deciding who is to be saved and who is not. In the USA, virtually all infants with any chance of survival are aggressively treated and stabilized until the future outcome can be certain. In addition, Infant Bioethical Review Committees are formed. In the UK such committees do not exist. Decisions are made by doctors together with parents. The practice in Australia is similar to that in the UK. It is recommended for Singapore that decisions should be made jointly by doctors and parents after thorough discussion. The formation of an Ethics Committee would lend support to the decision making. However, it is urged that prevention of low birth weight infants and congenital abnormalities would reduce the dilemma of the doctors. PMID- 2333550 TI - A case of aplastic anaemia associated with fulminant hepatitis B. AB - Aplastic anaemia is a rare complication of Acute Viral Hepatitis. This complication occurs during the resolving phase of the hepatitis or can be delayed as long as six months after resolution. Most cases reported were associated with Non A and Non B hepatitis. We report a case associated with Acute Hepatitis B. The onset of aplasia during the acute phase of hepatitis, and patient's subsequent progression to fulminant hepatitis were the interesting features of this case. PMID- 2333551 TI - Gelastic epilepsy--a case report. AB - Gelastic epilepsy is an uncommon phenomenon and it is particularly uncommon in adults. This paper describes a case of gelastic epilepsy in a middle-aged woman presented in a psychiatric hospital. A short history of the condition, clinical and electroencephalographic findings in gelastic epilepsy and causes of pathological laughter are discussed. PMID- 2333552 TI - Parathyroid carcinoma with steroid-suppressible plasma immunoreactive parathyroid hormone and human chorionic gonadotrophin. AB - A 31-year old male presented with bone pain, polyuria and a palpable nodule in the neck. Radiological examination showed generalised osteopenia, subperiosteal erosion and presence of bilateral renal stones. The essential chemical pathological changes were increased plasma calcium, mid-molecule immuno-reactive parathyroid hormone (iPTH), human chorionic gonadotrophin (hCG) levels. Surgical excision of the nodule revealed a parathyroid carcinoma. The uniqueness of this case is the steroid-suppressible plasma calcium, iPTH, and hCG levels. The diagnostic implications of the findings are discussed. PMID- 2333553 TI - A case of hyperhidrosis successfully treated with 20% aluminium chloride hexahydrate in 95% ethyl alcohol. AB - A 23-year old medical student presented with a history of excessive sweating from the palms and soles from the age of 16 years. He tried Propranolol but the relief lasted only 30 minutes and he developed breathing difficulty. He applied 20% Aluminium Chloride hexahydrate in 95% Alcohol during the nights and found a definite reduction in sweating. This method appears to be cheap, safe and convenient. PMID- 2333554 TI - Transphyseal linear ossific striations of the distal radius and ulna. AB - Radiologic and histologic analysis of transphyseal linear ossific striations of the distal ulna and radius showed that these striations consist of trabecular bone extending from the metaphysis across all zones of the physis into a small focus of fibrous and necrotic tissue within the epiphyseal cartilage. The focus appears to be a discrete area of epiphyseal ischemia with subsequent necrosis within and around the vasculature of a cartilage canal and probably represents a microscopic response to antecedent trauma that was insufficient to cause macrofailure (fracture) of the physis. The striations did not continue into the epiphyseal ossification center. The consequence is partial osseous bridging across the physis. This bridging is unlikely to cause significant growth damage, since in most cases it does not appear to extend farther into the secondary ossification center. PMID- 2333555 TI - Osteoid osteoma of the elbow. A review of six cases. AB - Six cases of osteoid osteoma of the elbow were reviewed to determine the spectrum of clinical, pathologic and radiologic findings. Since osteoid osteoma of the elbow may masquerade as a nonspecific synovitis, the diagnosis is challenging and frequently delayed. The histology is, however, indistinguishable from that of osteoid osteoma occurring in typical locations. The radiologic features of osteoid osteoma of the elbow include the following triad: (a) osteosclerosis, usually a dominant feature at initial imaging and typically enveloping the nidus; (b) joint effusion; and (c) periosteal reaction that can involve both the bone in which the osteoid osteoma arises and adjacent bones. Awareness of these features will facilitate correct diagnosis, thereby facilitating timely and appropriate treatment. PMID- 2333556 TI - Percutaneous intralesional brushing of cystic lesions of bone: a technical improvement of diagnostic cytology. AB - A modified bronchial brush is presented as a new cytologic method to improve the value of fine-needle aspiration biopsy in the diagnosis of cystic lesions of bone. Four female and six male patients ranging in age from 10 to 44 years were studied. In all cases intralesional brushing was percutaneously performed under fluoroscopic control with local anesthesia. Fine-needle aspiration biopsy preceded intralesional brushing and was performed as described elsewhere. The brush was driven into the walls and septa of an osteolytic lesion through a 14-G needle; material obtained was fixed and processed for cytological and/or histological examinations. PMID- 2333557 TI - Pigmented villonodular synovitis of the knee: computed tomographic appearances. AB - Five patients with pigmented villonodular synovitis (PVNS) of the knee demonstrate the value of preoperative, contrast medium-enhanced CT scanning. The technique is shown to be particularly useful in locating recurrent lesions and in demonstrating that popliteal and posterior calf masses are due to PVNS affecting the knee joint itself. In two of the five patients PVNS was not considered a possibility before the CT scan, and none had evidence of bone erosion on plain radiographs. In none of the patients was the unenhanced CT scan able to demonstrate evidence of decreased radiolucency due to fat within the tumour or density greater than the adjacent skeletal muscle, indicating haemosiderin deposits. PMID- 2333558 TI - Revascularization of femoral head ischemic necrosis with vascularized bone graft: a CT scan experimental study. AB - An ischemic necrosis of the femoral head was induced in 15 mongrel adult dogs using the technique described by Gartsman et al. [10]. Five weeks later, a free vascularized rib graft was transferred into the previously induced ischemic femoral head. High resolution computed tomographic scanning was used to evaluate revascularization 4, 8 and 12 weeks after grafting. The femoral head exhibited new vessel formation throughout the study. Arterial terminal branches arising from the rib graft medullary and periosteal circulations extended beyond the rib graft, entered the head, and reached the subchondral plate. Even where the rib graft did not replenish the central core of the head, there was vascular supply from the grafted bone's vascular tree. These results suggest that a free vascularized bone graft is able to revascularize an experimentally induced ischemic femoral head necrosis. PMID- 2333560 TI - Verbum sapienti. PMID- 2333559 TI - Spinal stenosis subsequent to juvenile lumbar osteochondrosis. AB - This paper describes eight patients with spinal stenosis associated with marked osteochondrous changes in the vertebral bodies due to juvenile lumbar osteochondrosis (Scheuermann's disease). In no case was the midsagittal or interpedicular diameter of the spinal canal indicative of bony stenosis. On the other hand, in the myelograms the sagittal diameter of the dural sac was in all cases significantly narrowed, a diagnostic sign of central spinal stenosis. Therefore, myelography should always be contemplated when osteochondrous changes are present and spinal stenosis is suspected clinically regardless of whether the spinal canal diameters are normal in plain films. PMID- 2333561 TI - Computed tomography evaluation of the sacroiliac joints in Crohn disease. Radiologic/clinical correlation. AB - Computed tomography (CT) was used in a prospective study of the sacroiliac joints in 86 patients with Crohn disease to determine the type and frequency of sacroiliac joint abnormalities present in this population. The CT findings were correlated with review of the clinical history in 64 patients. Computed tomography demonstrated changes of sacroiliitis in 29% of the study group. This high prevalence of sacroiliac joint abnormality was found even in those under 30 years of age. It exceeds the 11-19% previously reported from plain film examination, reflecting the greater sensitivity of CT. In the subgroup of 64 patients studied clinically, 19 (30%) had abnormal sacroiliac joints on CT, but only 2 (3%) reported symptoms related to the sacroiliac joints. PMID- 2333562 TI - Case report 586: Giant cell tumor of sphenoid bone. PMID- 2333563 TI - Case report 604: Osteofibrous dysplasia (ossifying fibroma) of tibia. PMID- 2333564 TI - Case report 605: Gluteal amyotrophy: a late sequela of intramuscular injection. PMID- 2333565 TI - Case report 606: Gas-filled subchondral cyst of ilium secondary to osteoarthritis of the sacroiliac joint. PMID- 2333566 TI - Case report 607: Synovial (osteo) chondromatosis of left hip joint and ileopsoas bursa. PMID- 2333567 TI - Case report 608: Retention of a bullet fragment within a traumatic pseudarthrosis, resulting in lead arthropathy and lead intoxication. PMID- 2333568 TI - Case report 609: Synovial (osteo) chondromatosis. PMID- 2333569 TI - [The founding and development of day care hospitals as integral structural subunits of therapeutic and preventive care institutions]. AB - The experience gained in the complex approach to the organization of day hospitals at curative and preventive facilities in Lvov and Lvov region is described. The problems in the delivery of in-patient care for the population formed the basis for the drafting of programme aimed at developing the network of out-patient departments of active treatment of patients. The description is given of the main components of day hospitals activities, schedule of work, indications and contra-indications for the treatment of patients. The work indicators of day hospitals of different types are provided. Highlighted is the importance of this vasically new and highly effective type of health care for the population. The data on the problem-oriented training of medical directors and physicians of day hospitals at the Faculty of Advanced Training of Physicians of the Lvov Medical Institute is provided, the emphasis being placed on the inclusion of issues on the organization of day hospital activities into the curricula for students and interns. PMID- 2333570 TI - [Ways to improve the management of hospitals]. AB - The article "Ways of improving the management of in-patient facilities" examines the organizational structure of management in respect to hospitals. A systems approach is used for management analysis. A hospital facility is defined as an hierarchical multilevel system of management. In this connection some problems concerning hospital management are considered: the multi-level character of management system, the specificity of management at each echelon of decision making process, the development of curative and diagnostic process technology, the problem of assessing management effectiveness at each hierarchical level. Attention is given to the training of hospital staff. Ways of improving the management of hospitals are determined for the purpose of raising the quality and effectiveness of in-patient care. PMID- 2333571 TI - [The information system "Interactions of drugs" and its role in drug therapy]. PMID- 2333572 TI - [Morbidity among workers and the organization of occupational medical services in shift-type work]. AB - The specific character of shift labour influences the structure of general morbidity and temporary disability caused by diseases. The most complete information is provided by periodic medical check-ups. In spite of professional selection, 30.2 percent of men and 62.0 percent of women have chronic diseases, 94.3 percent of diseases detected in men and 88.2 percent in women rank among eight classes of diseases, the most prevalent being diseases of respiratory and circulatory system. The relationship between morbidity, age, occupation and length of shift work is found. The specificity of health care delivery for shift workers is analyzed and ways of improvement are suggested. PMID- 2333573 TI - [Temporary disability among workers in bread-baking plants]. AB - A study of the impact of sanitary and hygienic, curative and preventive measures on the morbidity associated with temporary disability was conducted. Bread-baking plants N degrees 1 and N degrees 2 of the city of Vinnitsa were inspected, the number of workers there being 385 and 486, respectively, during 4 years. At the bread-baking plant N degrees 2, where general reconstruction of the production process had been carried out and special curative and preventive measures were being carried out, temporary disability was compared with analogous indicators in persons working at the bread-baking plant N degrees 1, where working conditions and the type of medical care remained unchanged. It was found out that the improvement of working conditions at the bread-baking plants and the carrying-out of special curative and preventive measures among workers resulted in reduction of morbidity especially in respect to the number of disability days. This association was mostly often found in cases of influenza, acute respiratory infections and chronic forms of broncho-pulmonary conditions. PMID- 2333574 TI - [Mass screening of coal miners with ischemic heart disease]. AB - As a result of epidemiological and clinico-functional studies occupational peculiarities of ischemic heart disease (IHD) among miners were detected. The role of a number of industrial factors in the development of arrhythmia with unfavourable prognosis was assessed. Persons at risk for development and progress of IHD were identified. A method of dynamic control over their cardiovascular system was suggested. The findings of the study formed the basis for a complex follow-up programme for miners with IHD. PMID- 2333575 TI - [The population's need for information on a healthy life style]. AB - The needs in healthy lifestyle information for professional groups (physicians, teachers, researchers, engineers) have been studied. Emphasis is being placed on some factors affecting the effectiveness of health education, i.e.: interest in information, awareness, satisfaction. The subjects of healthy lifestyle are specified in accordance with sources of information (radio, TV, films, J. of "Health", popular scientific publications). The priorities in choosing the source of information differ accordingly: physicians prefer special medical publications, teachers--popular scientific publications, researchers- interpersonal communication, engineers--radio, TV, films. PMID- 2333576 TI - [Automated preventive mass screening of neurotic disorders]. AB - The organizational phases in the operation of automated system of target screening for neurotic disorders under mass preventive examinations are described. In the process of screening persons at risk for neurotic disorders are identified and examined according to three classes system. Preventive measures are carried out by medical units. The use of this system improves the detectability of neurotic disorders. PMID- 2333577 TI - [Teaching the principles of Soviet law in postgraduate training of public health administrators]. PMID- 2333578 TI - [The MIC classification]. PMID- 2333579 TI - [Critical analysis of the routine use of the direct antiglobulin test in 22,517 cross-matching tests]. AB - Routine performance of the direct antiglobulin test (DAT) in pretransfusion testing (PT) is controversial. To evaluate its usefulness, we review the positive DATs found in 22,517 PT performed in our center in the last five years. DAT was positive in 330 PT (1.4%). Eluate studies gave information, not obtained from the rest of PT, in 6 cases. DAT predictive value is low (1.8% of the positive DATs, 0.02% of all PT). Although this predictive value is low, we keep on follow including DAT in PT but we have reduced eluate studies to 1) positive DAT of untransfused patients (to get information of the DAT prior to transfusion and to detected autoimmune haemolytic anaemias) and 2) positive DAT of previously transfused patients with previous negative DAT or changes in its reactivity (for the prompt detection of clinically significant antibodies). PMID- 2333580 TI - [Non-hemolytic transfusion reactions of the febrile type]. AB - The results of a hundred cases of febrile non haemolytic transfusion reactions are presented. We used the techniques that would best identify the different causes of these reactions. Most of these antibodies were anti HLA. Platelet and granulocyte-specific antibodies were seldom detected. The nature of the antibodies was specified by their different reactivity with the cells of various donors, by applying a panel of cells from typed donors and by absorption experiments. The study of the donor sera enabled us to elucidate the causes of some reactions. Nevertheless, in a significant percentage of cases it was not possible to determine the cause of the reaction, especially in the case of reactions secondary to platelet transfusions. Finally, we analyzed the reasons that could account for these phenomena. PMID- 2333581 TI - [Adult acute lymphoblastic leukemia: preliminary results of the LAL-86 protocol]. AB - The preliminary results of the LAL-86 protocol applied to 43 patients diagnosed of acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LL) between May 1986 and April 1989 are reported. Induction treatment consisted of one or two courses of vincristine, daunorubicin, prednisone, cytosine arabinoside and 6 thioguanine combination therapy. This phase was followed by consolidation treatment, in which VM-26, cyclophosphamide, BCNU and L-asparaginase were added to the former agents. Central nervous system prophylaxis was done with intrathecal methotrexate. Patients under 45 years of age with HLA identical sibs were subjected to allogeneic bone marrow transplantation (BMT) in the first complete remission (CR); when no HLA-identical sibs were available patients were randomised into autologous BMT or maintenance therapy. The remaining patients received maintenance chemotherapy. CR was achieved in 34 ALL patients (79%), 5 were refractory to treatment and 4 died during remission induction. Allogeneic BMT was carried out in 6 cases, autologous BMT in 3, and the remainders received chemotherapy. When performing this review, 7 patients had relapsed and the actuarial probability of 2-year duration of CR was 70%. Sixteen patients have died with a two-year disease-free survival probability of 60%. The preliminary results of the LAL-86 protocol are encouraging, but greater number of patients is needed, as well as a longer follow-up, to assess the effect of chemotherapy and compare these findings to the results of autologous or allogeneic BMT in the first RC. PMID- 2333582 TI - [Latin American regional reference materials for porcine heparin and bovine heparin]. AB - In agreement with the Regional Programme of Reference Materials of the Panamerican Health Organization the Instituto Nacional de Farmacologia y Bromatologia of Buenos Aires designed a study for the calibration of a Reference Material for Heparin, porcine, mucosal and a Reference Material for Heparin, bovine, mucosal. The assay methods used in this study were those described in the United States Pharmacopeia XXI Ed and British Pharmacopoeia 1980, Addendum 1983. The overall combined potency estimates of both heparin in preparations relative to 4th Int.St. was 1633.83 UI/ampoule (95% confidence limits 1609.70-1657.96 UI/ampoule) for porcine heparin and 1332.31 UI/ampoule (95% confidence limits, 1302.31-1361.77 UI/ampoule) for bovine heparin. The assigned unitage was 1630 UI/ampoule for the porcine Reference Material and 1330 UI/ampoule for the bovine Reference Material. PMID- 2333583 TI - [Posttransfusion thrombocytopenic purpura. 1st case described in Spain]. AB - Following a total blood transfusion, a 65 year old woman suffered severe thrombocytopenia characterized by purpura and haemorrhage. An immunological study revealed the existence of IgG and IgM type antibodies in the serum attached to the patient's platelets and to the eluate obtained from these. The specificity of the antibody was Zwa. The patient's platelets are Zwa-negative. Even in the remission phase of the thrombocytopenia it was still possible to obtain antibodies in the platelets of the eluate. Questions raised by this factor are discussed and, despite the difficulties posed, an attempt is made to find a coherent immunological explanation based on the results of the serological study. PMID- 2333584 TI - [Transfusion management of a patient with multiple anti-erythrocyte antibodies (anti-c + anti-K + anti-Fyb + anti-Jkb) subjected to a valvular reoperation using extracorporeal circulation]. AB - A woman with multiple anti-red cell antibodies (anti-c, anti-K, anti-Jkb, anti Fyb) due to previous transfusions was admitted to the hospital for valvular replacement. To ensure enough transfusional supply, a high number of packed red cell units was typed and screened prior to previous operation. Haemorrhagic complications developing during surgery led to transfusion of 32 blood units, 20 of them compatible. Besides this, measures directed to prevent complications derived from haemolytic disease were instituted. These included intravenous fluids and diuretics to maintain circulatory integrity and improve renal cortical blood flow. High-dose gammaglobulin was also administered in an attempt to decrease extravascular haemolysis. Despite therapy, severe adult distress respiratory syndrome caused patient's death nine days after surgery. We remark the need of storing frozen blood of low-frequency phenotypes in blood banks to face significant transfusional problems, providing sufficient numbers of antibody compatible blood. PMID- 2333585 TI - [Initial response to treatment with erythropoietin in anemia caused by chronic renal insufficiency]. AB - The achievement of recombinant human erythropoietin (r-HuEpo) supposed an important advance in the treatment of the anaemia of chronic renal failure. The results achieved with r-HuEpo in seven patients with chronic renal failure subjected to haemodialysis who required repeated blood transfusions are reported. The duration of treatment was 12 weeks at an initial doses of 50 U/Kg. A significant increase of haematocrit, red-cell count, haemoglobin, reticulocytes and platelets was attained. The decrease of serum iron, transferrin saturation index and ferritin in spite of oral iron therapy was striking. None of the patients required blood transfusion during the period of study, and all but one referred subjective improvement. No severe adverse effects were observed, except for one case of thrombosis of arteriovenous fistula, whose relation with this treatment is dubious. Although this is a short-term preliminary study, it can be inferred that r-HuEpo treatment is effective and free of major risks for the anaemia of chronic renal failure. PMID- 2333586 TI - [Megaloblastic anemia caused by a congenital deficiency of transcobalamin II]. PMID- 2333587 TI - [Pica caused by the ingestion of coffee beans]. PMID- 2333588 TI - [Syndrome of abnormal chromatin clumping in leukocytes]. PMID- 2333589 TI - [Apropos of the use of the Pink test in hereditary spherocytosis]. PMID- 2333590 TI - Assessing the economic status of the aged and nonaged using alternative income wealth measures. AB - This exploratory article examines several aspects of the complex problem of combining data on income and wealth into a single measure of economic well-being. Examples of income-wealth measures that have been used are described. Estimates of the economic well-being of age groups in the current period are presented for several measures. To examine the sensitivity of the results to the choice of method, those estimates are compared. In this article, wealth is defined to include only financial assets. Data from the 1984 Survey of Income and Program Participation are used. The economic status of the aged relative to the nonaged improves when the measure of resources is changed from income to a combined income-wealth measure. The amount of improvement depends on the income-wealth measure used. When medians are examined, the differences among most of the measures compared are not very large. For every measure compared, the median rises as age increases, then falls. When the percentage of each age group that is in the bottom of the distribution is examined for several income-wealth measures, the differences among measures are small. In general, these percentages are relatively high for the young and old age groups, and relatively low for the middle age groups. PMID- 2333591 TI - Recurrence in early gastric cancer. AB - In a retrospective study of 503 cases of early gastric cancer, 17 of the patients had died of a recurrence of the gastric cancer and 72 had died of unrelated causes. The cumulative recurrence mortality rates were 2.2% at 9 years for mucosal cancer and 8.4% at 8 years for submucosal cancer. The recurrence patterns of early gastric cancer were hematogenic metastasis to the liver, lung, or bone (nine cases), recurrence from lymph nodes (three cases), and recurrence in the residual stomach (five cases). Submucosal cancers with a macroscopically elevated appearance, lymph node metastasis, and evidence of vessel invasion were the high risk cancers for hematogenic recurrence, and adjuvant chemotherapy should be prescribed. Two cases of lymph node recurrence were attributed to inadequacy of lymph node dissection. Because metastasis to the group 2 lymph nodes was noted in 1.5% of cases of early gastric cancer and a macroscopic diagnosis of nodal status was inaccurate, complete dissection should be performed regardless of identification of metastasis. Five cases of recurrence in the residual stomach were attributed to overlooked lesions of multiple carcinoma and were detected at an advanced stage. Careful and regular postoperative follow-up is required to detect these recurrences at an early stage. PMID- 2333592 TI - Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. AB - Extensive liver resection for hilar bile duct carcinoma with jaundice has high morbidity and mortality rates because of postoperative liver failure. To minimize postoperative liver dysfunction, a portal venous branch was embolized before surgery to induce atrophy of the lobe to be resected and hypertrophy of the contralateral lobe in 14 patients with hilar bile duct carcinoma. Bile was drained before surgery in 11 patients with jaundice. Portal embolization did not produce major side effects, and moderate increases of serum transaminase activity or bilirubin returned to baseline values within 1 week. Hepatectomy with bile duct resection and lymphadenectomy was performed 6 to 41 days after embolization, at which time the embolized lobe was atrophied in 12 of the patients. Extended right or left lobectomy or left trisegmentectomy (10, 3, and 1 cases, respectively) with biliointestinal reconstruction was performed. One patient with jaundice and suppurative cholangitis died 30 days after hepatectomy. Another patient died 3 months after surgery of aggravated hepatitis. After surgery, no bile leakage occurred and hyperbilirubinemia was usually moderate and reversible. PMID- 2333593 TI - Problematic vascular reconstruction in liver transplantation. Part I. Arterial. AB - Arterial inflow is essential for graft function after liver transplantation. Sometimes the recipient celiac axis is not suitable for anastomosis, and in these cases a conduit from either the aorta or iliac artery is an alternative. We retrospectively reviewed 32 patients who required arterial conduits and compared them with a matched control group who underwent standard arterial reconstruction (donor celiac artery to recipient celiac artery). The indications and surgical technique for arterial conduits are presented. There were no differences in intraoperative vascular flow studies, postoperative liver function, or incidence of rejection in the two groups. There were, however, more deaths in the conduit group, two of which are related to the retropancreatic conduit technique, with the others caused by the patients' underlying condition at transplantation. There was no morbidity or death associated with the antepancreatic conduit techniques. We therefore believe the use of arterial conduits from the aorta or iliac artery, when placed antepancreatically, are safe and should be used without reservation when indicated. PMID- 2333594 TI - Problematic vascular reconstruction in liver transplantation. Part II. Portovenous conduits. AB - Eight of 265 orthotopic liver transplant procedures performed at this institution since December 1984 have used venous conduits to reconstruct an occluded portal system and supply portal blood to the allograft. The factors mandating the use of these conduits were variable, and several reconstructive techniques were used. We present a series of patients with various conditions in which portal conduits were indicated and describe and illustrate the inherent technical considerations. PMID- 2333595 TI - Effects of verapamil and degradable starch microspheres during hepatic artery infusion of doxorubicin. AB - Chemotherapeutic tumoricidal activity may be enhanced by altering regional blood flow between host organ and tumor by transient embolization with degradable starch microspheres (DSMs) or by altering cellular drug transport with drugs such as verapamil. This study evaluated the effects of intraarterial verapamil and DSMs on hemodynamics and doxorubicin tissue levels. Rabbits (n = 34) with hepatic VX-2 carcinomas underwent hepatic artery infusion of doxurubicin (3 mg/kg) alone, with two doses of verapamil, and with verapamil plus DSMs. Blood pressure and heart rate were monitored, and heart, liver, and tumor tissue was obtained after 30 or 90 minutes. After verapamil (2 mg/kg) alone, mean heart rate decreased but infusion of verapamil plus DSMs resulted in only a 14% decrease in mean heart rate. Thirty minutes after drug infusions, mean hepatic tissue levels of doxorubicin were increased significantly by 2 mg/kg of verapamil compared with results with 1 mg/kg of verapamil and those in control groups (p less than 0.05). Mean tumor doxorubicin levels were not significantly different with verapamil alone. Verapamil plus DSMs or DSMs alone resulted in significantly lower mean hepatic and myocardial levels and increased mean tumor/liver ratios of doxorubicin after 90 minutes, compared with results in control or verapamil-alone groups. These results suggest that hepatic tumor drug levels are more affected by changes in regional blood flow with DSMs than by cellular drug transport changes caused by calcium channel blockers such as verapamil. PMID- 2333596 TI - Ingrowing toenails: improving treatment. AB - Sixty-six patients with ingrowing toenails were randomly assigned to one of two treatment groups and followed up for 16 to 30 months after surgery. In group A 39 nail edges in 32 patients were treated by excision of the nail edge and chemical ablation of germinal matrix edge with 70% aqueous phenol. There were 34 patients in group B, in whom 46 nail edges and germinal matrix edges were surgically excised. In group A recurring symptoms developed in four (10%) nail edges, necessitating further surgery, and asymptomatic spicules developed in seven (18%) nail edges. Two (4%) nails in group B required reoperation and spicules developed in 10 (22%). Both procedures were performed as outpatient surgery, relieved pain and infection, and were acceptable to patients. At an average 2-year follow-up, both procedures yielded comparable results that were superior to those of simple avulsion. PMID- 2333597 TI - Gallbladder and gastrointestinal motility after hemorrhagic shock. AB - The alterations in fasting gallbladder and gastrointestinal motility during hemorrhagic shock were investigated. Eight opossums implanted with a gallbladder cannula, gastrointestinal bipolar electrodes, and a carotid catheter were subjected to hemorrhagic shock of 30 mm Hg for 60 minutes by the removal of arterial blood. Shed blood was reinfused after the shock period. Fasting gallbladder volume and gastrointestinal electrical activity were studied before, immediately after, and 24 hours after hemorrhagic shock. Control measurements demonstrated a slow-wave frequency maximal in the duodenum (18.1 +/- 1.1 waves/min), with a plateau in the proximal third of the small bowel, decreasing thereafter. The migrating motor complex (MMC) had a duration of 118 +/- 28 minutes. The average volume of the gallbladder before shock was 5.4 +/- 1.5 ml. Gallbladder volume fluctuated with the MMC, being maximal during phase I and minimal in phase III. The volume of blood removed to reduce mean arterial pressure to 30 mm Hg was 45 +/- 5 ml/kg. Immediately after the shock and blood reinfusion, slow-wave frequency decreased by 40% in the antrum and 25% in the small bowel. The MMC was of shorter duration (91 +/- 22 minutes; p less than 0.05), and gallbladder volume increased to 7.0 +/- 1.7 ml (p less than 0.05). Fluctuations in gallbladder volume during the MMC were absent. Twenty-four hours after shock, slow-wave frequency, MMC, and gallbladder volume had returned to normal and were not different from control measurements. Ischemic damage to the gastrointestinal tract is postulated as the cause of gallbladder dysfunction and altered intestinal motility after hemorrhagic shock. PMID- 2333598 TI - Do first- and second-year preclinical course scores predict student performance during the surgical clerkship? AB - The study proposed to determine if a preclinical basic science index comprised of anatomy, behavioral medicine, biochemistry, microbiology, pathology, pharmacology, and physiology courses or any one of these basic science courses would predict student performance during surgical clerkship. The basic science index demonstrated a correlation of 0.55 and 0.35 with the individual student's written and oral clerkship scores, respectively. A stepwise multiple regression using a backward stepping algorithm was applied; the dependent variables were oral and written clerkship scores, and the independent variables were the basic science courses. Microbiology, pathology, and physiology course scores were predictors of written score (R = 0.60). Pathology course scores were the sole predictor of oral score (R = 0.43). Medical student basic science performance was not a strong forecaster of performance on the surgical clerkship. The pathology basic science score was the only consistent predictor of performance on the written and oral evaluations given at the end of the clerkship. PMID- 2333599 TI - A simple, inexpensive technique for recording and reporting the operative experience of residents in a surgical training program. AB - The recording and reporting of resident operative experience have become increasingly important tasks for surgical training programs, and computerized data bases are now being used for these purposes. Despite their usefulness, these computerized systems can impose significant burdens in terms of manpower, time, and cost, particularly if the program director is to track diligently each resident's progress at intervals. Described here is a simple, inexpensive method for recording and reporting resident operative experience. This system can be maintained on a microcomputer with any one of a number of inexpensive, commercially available data base programs. PMID- 2333600 TI - Metastatic melanoma: an unusual cause of obstructive jaundice. AB - We report a patient with malignant melanoma metastatic to the supraampullar portion of the common bile duct. The unique aspects of this case include its clinical presentation masquerading as obstructive jaundice caused by a bile duct tumor and the finding of an isolated solitary recurrence metastatic to the bile duct. Cautions about the management of unusual gastrointestinal or pancreatobiliary lesions in patients with a history of melanoma are discussed. PMID- 2333601 TI - Impacted lower third molars and periodontal health. An epidemiological, methodological, retrospective and prospective clinical, study. AB - The main objective of this series of investigations was to study periodontal health of the adjacent second molars (M2) in cases of impacted lower third molars (M3) and after impacted lower third molar surgery. An epidemiological study, comprising 693 dentate individuals, was undertaken in order to obtain the prevalence, impaction and positional relationship of third molars in a normal Swedish population. The prevalence of all third molars in individuals aged 20 years was 77.0%. One in four of the vertically positioned third molars, three in four of the mesioangular, nine in ten of the distoangular and all those horizontally placed were impacted to some extent. 68.5% of the impacted third molars were in close proximity to the root of the adjacent second molars. In order to evaluate the precision and accuracy of the radiographic assessment of intrabony defects (IBD), i.e. the distance between the cemento-enamel junction and the bottom of the pocket to firm osseous contact, on the distal surface of M2, a methodological study was performed on 25 subjects. Using conventional free hand technique, intraoral radiographs were taken in the deepest part of IBD with and without a probe as indicator. Comparing the two sets of radiographs, the deviation was 1 mm or less in 87.9% of the cases. The radiopaque marker enhanced the accuracy of assessment of IBD to 96.7%. The effects of impacted lower third molar surgery on periodontal tissues of the M2 area were investigated in a retrospective clinical study comprising 215 subjects. The results two years postoperatively showed a higher prevalence of plaque, gingivitis and periodontal pockets on the distal surface of M2 than on other surfaces of the two molars adjacent to the extraction site. IBD greater than or equal to 4 mm were registered in 32.1% of the cases. The long term effects on periodontal tissues after impacted lower third molar surgery was investigated in a comparative retrospective study, two and four years postoperatively, comprising 51 cases. The improvement concerning postoperative IBD, between the two examinations, was mainly seen in individuals less than or equal to 25 years of age. No case in this age group increased in depth, while 29.6% of postoperative IBD deteriorated in individuals greater than or equal to 26 years. A multiple regression analysis was used to identify some predictors of postoperative IBD, and the material consisted of the 215 cases from the retrospective study.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2333602 TI - [Raising the quality of the therapeutic care for the population of an agroindustrial region]. AB - The system of the therapeutic services control in a rural region of this country has been developed and introduced over the recent three years. The key problem in the design of the system lay in search of criteria for the quality of the work of the treatment and prophylactic institutions and every medical worker, which would reflect the final results of their activities. Introduction of the system of the therapeutic services control brought about the reduction of temporary and steady work losses in patients with respiratory diseases as well as the decrease of the premature death rate because of respiratory and circulatory diseases. PMID- 2333603 TI - [A case of a giant aneurysm of the coronary artery]. PMID- 2333604 TI - [A case of Caplan's syndrome in a miner]. PMID- 2333605 TI - [A case of the adult respiratory distress syndrome during extreme total body cooling and the aspiration of cold fresh water]. PMID- 2333606 TI - [The main indications for referring patients to a day hospital]. AB - The authors review the main tasks of the day hospitals and the main principles of their work. Distinguish the main groups of patients treated at the day hospitals in 1983-1987. The mean times required for the treatment at the day hospitals and specialized hospitals of the city, gastroenterological, pulmonological, nephrological and vascular surgical, are under comparison. PMID- 2333607 TI - [Practical games as a form for problem-oriented instruction in a department of internal diseases during undergraduate training]. PMID- 2333608 TI - [Problems in organizing an academic course on the care of patients in a department of treatment and prevention]. PMID- 2333609 TI - [A method for making up instructional tests on situational tasks of differential diagnosis]. PMID- 2333610 TI - [The consultative diagnostic center. The endoscopy department (the potentials and limitations)]. PMID- 2333611 TI - [The rational utilization of the potentials of a department of clinical chemistry in a diagnostic center]. PMID- 2333613 TI - [Trends in the development of social public health]. PMID- 2333612 TI - [The hemodynamic effects of a number of new hypotensive preparations]. AB - Assessment of the initial data on hemodynamics in patients with stage II essential hypertension made it possible to differentiate indications for the use of some new hypotensive drugs. In the treatment of patients with stage II essential hypertension, preference should be given to arelix and minipress in case the total vascular resistance is initially high, whereas in hypertension of ejection, it is better in long-term treatment of patients with stage II essential hypertension, that the drugs producing an effect on the stroke volume of the heart, namely arifon, and tobanum, may be applied. All the drugs enumerated exert a negligible effect on the microvascular blood flow. PMID- 2333614 TI - [The potentials for curing atrial flutter by the combined use of transesophageal electrical stimulation and anti-arrhythmia preparations]. AB - Potentialities of the recovery of the sinus rhythm were studied in 21 patients with atrial flutter (AF) using frequent transesophageal electric cardiac pacing (TEEP) per se and after intravenous injection of ritmilen and novocainamide under outpatient conditions. TEEP made it possible to arrest AF in 24% of patients and to transform flutter into steady atrial fibrillation in 48% of patients. In 28% of cases, the pacing turned out ineffective. Subsequent administration of antiarrhythmic drugs made the rhythm return to normal in 24% of patients, whereas repeated TEEP conducted after drug administration in additionally 33% of patients. The efficacy of frequent TEEP combined with administration of ritmilen and novocainamide amounted to 81%. PMID- 2333615 TI - [The effect of plasmapheresis and the plasmasorption and immunosorption of low density lipoproteins on the humoral immunity function of patients with hereditary hypercholesterolemia]. AB - It has been shown that prolonged use of plasmapheresis with a 7-day interval in patients with hereditary hypercholesterolemia is potentially dangerous because of possible development of immunodeficiency. LDL plasmasorption and immunosorption produce a beneficial effect on the concentration of immunoglobulins. It is assumed that immunosorption permits the elimination not only of lipoproteins but also lipoprotein-containing immune complexes from the blood channel. PMID- 2333616 TI - [Antibodies to DNA and deoxynucleoprotein in Sjogren's disease and syndrome]. PMID- 2333617 TI - [New approaches to local antirheumatic therapy]. AB - Local antirheumatic therapy is viewed as an important component in the total system of the treatment of rheumatic diseases. Drug-induced synovectomy, local anti-inflammatory, antifibrotic and potential immunosuppressive therapy are analyzed. Special attention is paid to local therapy based on the use of dimethyl sulfoxide. The effects of local and general treatment are realized at least partially by means of the same mechanisms. There is possibility to improve the results of general therapy at the expense of goal-oriented local treatment without producing any influence on its tolerance. In fact, every patient with rheumatoid arthritis or other articular disease should be regarded as a potential candidate for local anti-inflammatory therapy. PMID- 2333618 TI - [Laser therapy in rheumatology]. PMID- 2333619 TI - [Emotional-volitional training in the combined treatment of patients with rheumatoid arthritis]. AB - The development of placebo effect was found to be related to the psychological status and neurophysiological features of the body. This made it possible to elaborate the disadaptation hypothesis of the disease development and a total systems approach to its treatment, characterized by the necessity of conducting both conventional (aimed at suppression of the autoimmune process and inflammation) and activation therapy. The method of emotional volitional training (EVT) designed by the authors is advanced as one of the components of the activation therapy lying in the use of music therapy, auto- and heteropsychic actions together with application of an optimal variety of group physical training. Application of the EVT to the treatment of 86 patients with rheumatoid arthritis enabled the drug dosage to be reduced by as many as 50%, to improve the patients' mental status and to enhance work fitness, promoting the decrease of the hospital treatment by 4-5 days and prolongation of the remission from 6 months to 1.5 years. PMID- 2333620 TI - [The serum prolactin levels of men with systemic lupus erythematosus and rheumatoid arthritis]. PMID- 2333621 TI - [The clinico-functional effectiveness of calcium antagonists in correcting the bronchial hyperreactivity of bronchial asthma patients]. AB - In 46 bronchial asthma (BA) patients, a study was made of the effects of calcium antagonists (CA) (corinfar, perdipine) on bronchial sensitivity and reactivity determined on bronchospasm induction with the increasing doses of acetylcholine. A single intake of 20 mg of a CA in BA patients significantly improved bronchial sensitivity and reactivity (the rise of the PD25 and the decline of the alpha angle). 20 patients were treated with corinfar for two weeks after administration of the basic therapy. As a result, the clinical status as well as bronchial sensitivity and reactivity improved in the majority of BA patients. While assessing the efficacy of the treatment with corinfar after half a year it was established that in 9 out of 13 BA patients, the PD25 increased and the alpha angle diminished. Thus, CA reduce bronchial hypersensitivity and hyperreactivity to acetylcholine in BA patients. PMID- 2333622 TI - [The clinical pharmacology of a new Soviet preparation theopek]. PMID- 2333623 TI - [The clinico-immunological indications for treating bronchial asthma patients with thymalin]. PMID- 2333624 TI - [The use of a respiratory regulator in the combined therapy of obstructive lung diseases]. AB - The authors review a method for the treatment of patients suffering from nonspecific pulmonary diseases associated with the obstructive syndrome by means of a respiratory regulator which permits the building of positive pressure of 2-4 cm H2O throughout expiration. External respiration, gas exchange and hemodynamics were explored in 30 patients with chronic obstructive bronchitis and in 30 patients with bronchial asthma treated by the respiratory regulator. There were clinical and functional data indicating the lowering of bronchial obstruction: an increase of the lung capacities, improvement of the velocity indicators, and improvement of the ventilation-perfusion correlations in the lungs. PMID- 2333625 TI - [The use of thermal vibromassage of the chest cavity in patients with chronic obstructive bronchitis for improving their tolerance for physical loads]. AB - According to the bicycle ergometry data the greater part of patients with chronic obstructive bronchitis are characterized by reduced physical work fitness. The latter one was found to rise under the effect of thermal vibromassage of the chest at a frequency of 30 Hz. The method has been elaborated and the advisability of its use has been theoretically based. The given method can be applied to the rehabilitation treatment of patients, particularly before exercise therapy. PMID- 2333626 TI - [The clinico-immunological efficacy of dioxidine in the combined treatment of acute abscessing pneumonias in persons who abuse alcohol]. AB - The results of clinico-immunologic studies of the efficacy of dioxidin in persons abusing alcohol have demonstrated that unlike antibiotics, dioxidin does not provoke any immunosuppressive disorders. It is recommended that dioxidin should be included into multimodality treatment of patients with acute lung abscesses, abusing alcohol. PMID- 2333627 TI - [The use of hyperbaric oxygenation in treating viral hepatitis B and the reaction of the blood leukocytes]. AB - A total of 75 patients with virus hepatitis B of medium gravity were examined for the effect of HBO on the clinical course of the disease and blood leukocyte reaction. This reaction was tested on the basis of a complex of rosette-forming and cytochemical tests. HBO was found to produce a favourable effect if used at the early stages of the treatment (the first week of hospitalization). The effect consisted in significant reduction of the rate of exacerbations and residual phenomena. HBO provoked a decrease in the content of T and B lymphocytes by the 10th session of the treatment. A close relationship was revealed between HBO efficacy and the initial level of functional metabolic activity of leukocytes. The use of HBO was always accompanied by the rise of that activity during the treatment. The use of HBO at later times of the treatment (weeks 4-5) did not produce any well-defined clinical effect. Thus, HBO (8-10 sessions, pressure 1.5 absolute atmosphere, exposure 45 min) may be indicated as a prophylactic measure in respect of an unfavourable disease course with regard to the patients' selection on the basis of a complex of cytochemical tests. PMID- 2333628 TI - [Experience with the use of plasmapheresis in the combined treatment of children with the crush syndrome]. AB - Plasmapheresis (PP) was applied to the treatment of 5 children aged 6-14 years with the crush syndrome. The multimodality treatment using antibiotics, erythrocytic mass, rheologically active preparations, hemodialysis and blood rheologically active preparations, hemodialysis and hemoperfusion carried out for 6-7 days before PP did not bring about any appreciable improvement of the patients' status. The patients failed to get rid of anuria and manifested the signs of increasing intoxication. The treatment with PP consisted of 1 to 6 procedures, in the course of which 70 to 85 of the design volume of the circulating plasma was removed. The use of PP resulted in the disappearance of myoglobin from the patients' blood and urine, in the normalization of the coagulogram, a considerable decrease of the content of medium molecules, and in the appearance of the first urine towards the end of the procedure. Thus, the introduction of PP into multimodality treatment of the crush syndrome made it possible to eliminate anuria, disseminated intravascular coagulation, and to noticeably reduce intoxication and to clear the blood off myoglobin. PMID- 2333629 TI - [The effect of nifedipine at the initial stage of its use on kidney function in patients with chronic kidney failure]. PMID- 2333630 TI - [The typical features and clinical characteristics of Reiter's syndrome with a nonvenereal origin]. AB - Analysis of the clinical picture in 37 patients with Reiter's syndrome unrelated to venereal urethritis showed that in the majority of cases, it was preceded by acute intestinal infection which occasionally ran an unmarked course. The difficulties in diagnosing Reiter's syndrome were caused in some patients by the fact that in the disease debut, conjunctivitis and urethritis were little manifest and of short duration or occurred at the later stages, especially where the triad was preceded by the provoking factors, such as supercooling and nasopharyngeal infection. Also, in the acute phase of the disease, the patients demonstrated catarrh of the upper respiratory tract, the signs of myocardial injury and some symptoms characteristic of other rheumatological diseases. In this connection attention is drawn to the necessity of inquiring after the patients' health and sensations in doubtful cases, including the elucidation of the epidemiological anamnesis, thorough examination of the patients on admission to hospital and during the treatment to specify both the main and additional signs of Reiter's syndrome, and analysis of the disease course. PMID- 2333631 TI - [A possible variant of a false diagnosis of infection with the human immunodeficiency virus]. AB - The authors describe a patient who demonstrated positive blood responsiveness to the nuclear antigens of human immunodeficiency virus (HIV) (p17, p31 and p55), observed steadily for 1 year and 4 months. The donor's disease history consideration made it impossible to include him in one of the known groups at risk for HIV infection whereas the lack of any changes in immunoblotting enabled one to exclude the diagnosis of HIV infection. The given case and other similar cases form the basis for introducing the second parallel screening during blood testing for HIV infection to bar the use of such blood for transfusion. PMID- 2333632 TI - [Herpes zoster in cancer patients]. AB - In cancer patients, the development of herpes zoster (HZ) is accompanied by protracted period of skin rash exudation and by slower scab rejection. Unlike hematological patients, no unfavourable outcomes with infection generalization are observed. The disease is associated with the rise of the content of total IgM, IgA (to a lesser degree) and with the normal level of IgG. There is a tendency towards the reduction of the count of T and B lymphocytes. The cases of primary diagnosis of a malignant tumor in HZ patients are more frequent (2 out of 36). PMID- 2333633 TI - Anabolic steroids in athletics. AB - Steroid abuse in athletics is one of the most pressing health problems in sports today. Many athletes believe that they must take steroids in order to compete, even though scientists are divided on the question of whether steroids increase strength. This paper reviews the history of anabolic drug use in sports, the types of steroids and amounts used, their intended effects, and the possible side effects. PMID- 2333634 TI - Steroid use by athletes shows poor judgment, lost integrity. PMID- 2333635 TI - 'Idiopathic' nephrotic syndrome is not always idiopathic. PMID- 2333636 TI - Physicians' attitudes toward generic drug substitution by pharmacists. AB - Physicians in Southeast Texas were surveyed to obtain information on attitudes and practices concerning generic drug substitution. Questionnaires were sent to all practicing primary care physicians in the area, and responses were received from about 36% of them. The investigation revealed that a large percentage of physicians did not readily permit substitution. Two major reasons given for not permitting substitution were concerns about therapeutic inequivalency and doubts about pharmacists' ability to substitute safely. PMID- 2333637 TI - Pediatric AIDS: impact on health systems. AB - For 9 years we have recognized HIV infection/AIDS as an unstoppable epidemic affecting infants, children, and adolescents as well as adults. Now we see the tremendous impact of this disease on the health systems of this country. During these past 9 years, we have witnessed the transformation of the epidemic from one primarily affecting male homosexuals to one invading the average US family through heterosexual and vertical transmissions and through needle-sharing practices of intravenous drug abuse. It has been estimated that 2% to 3% of the HIV infection/AIDS cases involve the pediatric age group. If 1.5 million Americans have HIV infection by 1991, as predicted, we should anticipate 30,000 to 45,000 infected pediatric patients by the end of that year. What has been the impact of this epidemic on the health systems involved in care, prevention, and research of pediatric HIV infection/AIDS? This article investigates that question. PMID- 2333638 TI - IRS alters approach to gift tax. AB - Very often the IRS asks taxpayers to "prove" certain items on their tax returns. A recent court case clarifies how much time the IRS has to request this proof for gift-tax returns. A discussion of this case, and a suggestion on how to better prove payment of income taxes, are contained in the following vignette. PMID- 2333639 TI - [Updating the autopsy procedure]. PMID- 2333640 TI - [To quit smoking--is it possible?]. PMID- 2333641 TI - [Snowmobile accidents]. PMID- 2333642 TI - [The snowmobile--only for fun? Registration of snowmobile accidents in Western Finnmark 1988-89]. AB - Driving a snowmobile seems to be associated with a high rate of injury and serious injuries. During the winter season 1988-89, every snowmobile-related injury that had required medical care was registered prospectively in a population of 47,500. 62 persons were injured, mostly men. The majority were young people, and most injuries occurred when the snowmobiles were used for recreation, and at the weekend. 11% of the drivers appeared drunk. 26% were hospitalized. Fractures were the most frequently registered injury, and 16 persons suffered head injuries. A number of other serious injuries were also registered. The rate of injury per registered snowmobile was high compared with the rate of road traffic injuries during the same period. PMID- 2333643 TI - [Smoking cessation using nicotine gum]. AB - Smoking cessation in matched groups with (n = 54) versus without (n = 63) nicotine gum took place in order to test the gum with regard to abstinence rate and experienced value. In all, 71% quit smoking, 23% reduced consumption to half, while in 6% there was no change. The frequency was approximately even in the two groups. One month later, 79% of the quitters in the nicotine gum group still remained abstinent, compared with 54% in the control group (p less than 0.05). Six months later these frequencies were reduced to 34% and 20% respectively. Side effects were reported among one third of the users (aching of the jaw, sore throat), while two thirds found the gum useful. These persons found it hard to be without the gum, and that it reduced the craving for tobacco. In other words, it renders smoking cessation more certain. PMID- 2333644 TI - [Malignant melanoma--a warning. How to reduce mortality?]. AB - Incidence of malignant melanoma of the skin has risen rapidly during the last decades. Mortality rates are also rising, although not so much as incidence rates. There is strong evidence that exposure to sunlight is a major factor in the etiology of melanomas. There appears to be no direct cumulative dose-response relationship, except in the case of lentigo maligna melanoma. Episodes of sunburn among children and young individuals seem to be more important as an etiologic factor for melanoma than chronic exposure to the sun. Very high risk of melanoma exists in persons with dysplastic nevus syndrome. Persons with giant congenital nevi are also at increased risk. However, many melanomas arise de novo. It is our intention to reduce mortality by screening families at risk, by early detection and treatment of melanomas, and by education. PMID- 2333645 TI - [Myasthenia gravis and thymoma]. AB - The article reviews age, symptoms, diagnosis, response to thymectomy, survival and concomitant disease in 15 patients with myasthenia gravis and thymoma registered in the period 1947-87. The thymomas were locally asymptomatic. The combination of roentgenological investigation and serological detection of nonreceptor muscle antibodies indicated the presence of a thymoma in 13 out of 14 patients. In eight out of nine patients with benign thymomas, myasthenic symptoms improved after thymectomy. Six out of eight patients with noninvasive thymomas survived five years, as opposed to one out of four with invasive thymomas. Associated disorders included polymyositis, myocarditis, parkinsonism and amnesia. PMID- 2333647 TI - [Experiences of pulmonary disease on jet planes]. AB - A group of patients with serious chronic diseases of the chest (n = 18) travelled from northern Norway to Yugoslavia for treatment (approximately four hours air travel and 16 hours total travel). The group included patients with asthma, chronic obstructive pulmonary disease, sequelas after tuberculous disease and resections for lung cancer. Minute lung function tests were performed before departure. SaO2 was monitored by pulsoximetri during the flight. All patients experienced a fall in SaO2 during the flight. Patients with restrictive pulmonary disease or combined restrictive/obstructive disease fell significantly lower than the rest of the group (p less than 0.001), and they experienced serious discomfort. Recommendations for minimum lung functions are FEV1 greater than 1.0 liter, PaOa greater than 9.3 kPa and PCO2 less than 7.0 kPa. PMID- 2333646 TI - [Heart disease in myasthenia gravis]. AB - The symptoms in myasthenia gravis are mainly due to reduced function of skeletal muscle. But some patients, especially those with a thymoma, have symptoms or signs of myasthenia-related heart disease. Some of our patients with histological myocarditis have died suddenly and unexpectedly. The frequency of electrocardiographic abnormalities among myasthenic patients has increased. Patients with myasthenia gravis should be subjected to cardiac monitoring after thymic surgery and during myasthenic crisis and other severe illnesses. If clinical examination leads to suspicion of myocarditis, the patient should receive immunosuppressive therapy. PMID- 2333648 TI - [Skateboard injuries in Oslo]. AB - Skateboards were allowed in Norway from May 1989 after being prohibited for 11 years. The media gave the sport extensive coverage due to the presumed large number of accidents suffered by its partisipants, and critics wanted the sport banned. We registered all skateboard injuries referred to Akuttetaten in Oslo. 113 patients were examined during a four month period. 63% were in the age group between 11 and 14. There were no serious accidents. 42 (37%) had upper/lower limb fractures, 14 required reduction. Four had head trauma with temporary loss of consciousness. The rest suffered minor traumas, distortions, etc. The results of the registration are discussed with reference to international literature. PMID- 2333649 TI - [Pancreatic duct prosthesis]. AB - Endoprothetic stenting of the pancreatic duct is reported in limited series. Twelve patients are presented here. In five patients with confirmed or suspected pancreatic malignancy, pain and diarrhea subsided or disappeared, and two patients had a temporary gain in weight. Four patients with chronic pancreatitis all experienced relief of symptoms. One patient with a pancreatic abscess improved temporarily. A postoperative pancreatic fistula healed within two weeks. One patient with a stone in the pancreatic duct became temporarily free from pain. Two patients had minor complications. Efficiency of pancreatic drainage is difficult to evaluate. However, all our patients seemed to benefit from the treatment. PMID- 2333650 TI - [Alfentanil. A potent and controllable opioid]. PMID- 2333651 TI - [Physicians' contact with the drug industry. An interview among general practitioners]. AB - Seventy-eight general practitioners were interviewed by questionnaire on the subject of contact between general practitioners and the pharmaceutical industry. There seemed to be a certain discrepancy between the existing working instructions of the pharmaceutical industry and the needs of the general practitioners. Nevertheless, the overall contact seemed to be satisfactory. Most general practitioners wished to be visited by representatives of the pharmaceutical industry, preferably qualified ones. The opinions of male and female doctors were generally the same. PMID- 2333652 TI - [Use of ICD-9 in Norwegian hospitals. A questionnaire]. AB - In 1988 a questionnaire was sent to every Norwegian clinical department to obtain a nationwide overview of the current use of the International Classification of Diseases (ICD-9), as recommended by the Director General of Health. The departments were asked about coding and registration routines, follow-up and control, and if they provided training in using the ICD-9. Questions were also asked concerning the advantage of the classification, any difficulties encountered, and if abbreviated code lists had been made for everyday use. Other comments were also welcomed. The main results of the study show that the majority of clinical hospital departments now use ICD-9. About 65% of the departments who took part in the study find it a useful tool, but there is no marked general enthusiasm. PMID- 2333653 TI - [Coding of diagnoses according to ICD-9]. AB - The paper gives an account of the principal structure and main characteristics of the International Classification of Diseases, 1975 Revision (ICD-9), which has been used by Norwegian hospitals and the Norwegian public health administration since 1987. ICD-9 coding rules are examined, mainly the basic rule that transformation of diagnoses to codes should be complete, or should result in the smallest possible loss of information and convey no invented information. The rule of multiple coding states that, if possible, diagnoses which can be coded only with much loss of information should be divided into smaller entities. The ICD-9 code of the diagnosis comprises the codes of the set of entities which most reduces loss of information. If more than one set of entities represents the same amount of reduction in loss of information, then the set with the smallest number of entities should be chosen for reasons of reproducibility. The paper also presents the two procedures by which the corresponding ICD-9 category and code for a given diagnosis can be searched and identified. PMID- 2333654 TI - [Emergency medical services]. PMID- 2333655 TI - [With amalgam in the teeth. Adverse effects of amalgam]. PMID- 2333656 TI - Studies of novel pentacyclic heterocyclic steroids: Part XXI. Total synthesis of racemic benz[3,4]-6-oxaestra-1,3,5(10),8-tetraen-17 beta-ol. AB - 1-Oxo-4-oxa-1,2,3,4-tetrahydrophenanthrene is converted into racemic benz[3,4]-6 oxaestra-1,3,5(10),8-tetraen-17 beta-ol in 45% yield. PMID- 2333657 TI - The chemistry of 9 alpha-hydroxysteroids. 3. Methods for selective formation and dehydrations of 17 beta-cyano-9 alpha,17 alpha-dihydroxyandrost-4-en-3-one. AB - Two methods to produce the 17-cyanohydrin, using potassium cyanide in acetic acid/methanol or acetone cyanohydrin with aqueous sodium hydroxide, were followed with 9 alpha-hydroxyandrost-4-ene-3,17-dione, both providing 17 beta-cyano-9 alpha,17 alpha-dihydroxyandrost-4-en-3-one. The selectivity of one of these methods, that which uses acetone cyanohydrin, is not in agreement with a comparable reaction with the 9 alpha-unsubstituted androst-4-ene-13,17-dione to give the 17 alpha-cyano-17 beta-hydroxy product, as reported in the literature and confirmed by us. The 9 alpha-hydroxy and 17 alpha-hydroxy groups were used for the regioselective introduction of 9(11)- and 16(17)-double bonds by dehydrating 17 beta-cyano-9 alpha,17 alpha-dihydroxyandrost-4-en-3-one under different conditions. PMID- 2333658 TI - Synthesis of aminosterols and their derivatives. AB - Reactions of steroidal epoxides such as 5,6 alpha-epoxy-5 alpha-cholestane (I) and its 3 beta-chloro (II) and 3 beta-acetoxy (III) analogs with urea in dimethylformamide afforded 6 beta-amino-5 alpha-cholestan-5-ol (IV-VI), 6 beta amino-N-formyl-5 alpha-cholestan-5-ol (VII-IX), and 6 beta-amino-N-amido-5 alpha cholestan-5-ol (X-XII), along with the 5 alpha-cholestane-5,6 beta-diol (XIII XV). In addition to these compounds, the 3 beta-acetoxy analog also afforded the N-carboxyl derivative (XVI). PMID- 2333660 TI - Synthesis of 2-hydroxyestriol monoglucuronides and monosulfates. AB - The ring A monoglucuronides and monosulfates of 2-hydroxyestriol were synthesized from 2-hydroxyestriol 16,17-diacetate by means of the Koenigs-Knorr reaction with methyl alpha-acetobromoglucuronate and sulfation with sulfur trioxide-pyridine complex, respectively. The conjugated positions of these compounds were definitely established by conversion to 2-hydroxyestriol monomethyl ethers by methylation, then enzymatic hydrolysis. The ring D monoglucuronides and monosulfates of 2-hydroxyestriol were also prepared from 2-hydroxyestriol 2,3 dibenzyl ether by glucuronidation and sulfation in a similar fashion followed by debenzylation, respectively. The positions of conjugation were established on the basis of their 1H-nuclear magnetic resonance spectral data. PMID- 2333659 TI - Synthesis and biochemistry of fluorescent aromatase inhibitors. AB - Effective aromatase inhibitors have been developed that contain aryl functionalities at the 7 alpha-position of the steroid nucleus. The exact interactions of 7 alpha-substituted androstenediones with the active site of aromatase is unknown. Fluorescent derivatives may provide a useful spectroscopic method for examining the binding of these inhibitors to the microsomal complex and purified aromatase protein. Dinitrophenyl, dansyl, and naphthyl derivatives of 7 alpha-(4'-amino)phenylthio-4-androstene-3,17-dione and androstenedione were synthesized as potential fluorescent agents. An in vitro assay with human placental microsomes was used to evaluate aromatase inhibitory properties. These fluorescent compounds were effective competitive inhibitors and have apparent Ki values ranging from 24.1 to 86.7 nM. PMID- 2333661 TI - Effect of strain and age on in vitro proliferation of murine thymus-derived macrophages. AB - In our laboratory we developed a technique which enabled us to carry out long term cultures of pure murine thymus-derived macrophage (TDM phi) populations having morphology, phagocytic capacity and surface markers characteristic of mononuclear phagocytic cells. We cultured thymic cells derived from various mouse strains on extracellular matrix coated tissue culture dishes, in the presence of conditioned medium. These cells developed into discrete TDM phi colonies and demonstrated a different proliferation rate. The TDM phi bearing haplotype H-2k (C3H/Crgl, CBA/LAC) proliferated more rapidly than TDM phi derived from mouse strains bearing the haplotypes of H-2b (C57BL/6), H-2d (BALB/c) and H-2k/d (A/J). To evaluate more precisely the number of precursor cells which generated TDM phi colonies and to study their growth kinetics, thymic cells were cultured in soft agar. A relatively large number of TDM phi precursor cells was derived from thymuses of H-2k haplotype origin. These precursor cells manifested a high rate of proliferation as compared with precursor cells of other murine haplotypes studied (H-2b, H-2d). These observations suggest that macrophage precursor cells are also located in the thymus and their numbers are controlled by genetic factors. We also observed a correlation between the number of precursor cells and the age of the mice. The percentage of TDM phi in new born and young mice was approximately four times higher than that found in older mice. It, therefore, seems that the degree of thymic involution affects the number of thymic macrophage precursor cells, which might indirectly affect thymocyte maturation and/or differentiation. PMID- 2333662 TI - Nuclear progestin receptors in rat thymic tissue. AB - The thymus and its associated endothelial cells and lymphocytes act as an important immunological tissue. The endothelial cells of the thymus have been reported to synthesize cytoplasmic progestin receptor in response to estrogen priming. To measure nuclear progestin receptor, female rats were castrated and primed for 3 days with estradiol benzoate (30 micrograms/0.1 ml/d) and immediately before sacrifice injected subcutaneously with 0.2 mg of progesterone. By Scatchard plot analysis we found that specific progestin receptor (KA = 0.89 +/- 0.10 x 10(9) M-1) was present in the KCl-nuclear extract. The concentration of nuclear progestin receptor was found to be in the range of 312.6 +/- 49 fmole/g tissue (n = 9, 1 hour after progesterone injection) while the nuclear receptor was significantly reduced (approximately 44 fmol/g tissue) in the oil treated controls. This level verges on the limits of sensitivity for this assay. For cytoplasmic progestin receptor the concentration was 3.46 +/- 0.20 pmole/g tissue in oil treated controls (n = 14) and 3.36 +/- 0.20 pmole/g tissue in progesterone treated animals (n = 24). The KA of this thymic cytoplasmic progestin receptor was 1.35 +/- 0.06 x 10(9) M-1. By competition assay, the relative binding affinity of nuclear progestin receptor was: R5020 (a potent synthetic progestin) (100%), progesterone (9%), testosterone (0.56%), corticosterone (0.53%), estradiol-17 beta (0%). It is concluded that thymic reticuloepitheleal cells contain nuclear progestin receptor and this finding supports the hypothesis that progesterone, like other sex steroids may play a regulatory role in thymic cell function. PMID- 2333663 TI - Fetal liver cell transplantation in scid mice. AB - Mice with severe combined immunodeficiency (CB 17 scid) received isogeneic and allogeneic fetal liver cell transplantation. Immunological reconstitution was followed by immunoglobulin production, mitogen-induced proliferation, spleen and thymus lymphoid recolonization. Scid mice injected with isogeneic fetal liver cells showed normal IgM, IgG production and subnormal Con-A induced proliferation. Lymphoid organs were gradually repopulated. Mice having received allogeneic stem cells presented normal IgM and IgG secretion. They still had no mitogen-induced lymphocyte stimulation, two months after fetal cell transplantation, despite satisfactory repopulation of spleen and thymus. Reconstitution of cell-mediated immunity may be somewhat slower following allogeneic than isogeneic stem cell transplantation. PMID- 2333664 TI - Biochemical characterization of thymic hormones in thymoma tissues. AB - Thymic hormones induce T-cell markers and functions. These polypeptide hormones have also been shown by means of immunocytochemistry to localize in thymic epithelial cells. Employing biochemical isolation procedures, we have studied the concentration of two thymic hormones, prothymosin alpha and thymosin beta 4, in the thymus of three thymoma patients. After a brief boiling step, thymic tissue obtained from each patient was individually homogenized and centrifuged. The supernatant was then fractionated by gel filtration on Sephadex G-100 and further purified by reversed-phase high performance liquid chromatography (HPLC). Purified components were characterized by amino acid analysis and HPLC tryptic peptide mapping. Our results revealed that the extract from benign thymoma had both prothymosin alpha and thymosin beta 4, similar to normal human thymus. However, the thymus from a patient with invasive malignant thymoma contained only thymosin beta 4, but no prothymosin alpha. In the extract from an undifferentiated carcinoma, neither prothymosin alpha nor thymosin beta 4 could be detected. These results disclose the possible correlation of thymic hormones and the type and differentiation stage of thymomas. The inability of malignant thymic tumors to produce normal amounts of thymic hormones may contribute to their etiology. It is suggested that information on the thymic hormone content might add a new parameter to pathological diagnosis in thymic tumors. PMID- 2333665 TI - Consensus meeting agrees distribution of 5-HT3 receptors in mammalian hindbrain. PMID- 2333666 TI - Enantiomers: how valid is Pfeiffer's rule? AB - In the 1950s Pfeiffer observed that the relative potencies of the enantiomers (mirror-image isomers) of several drugs appeared to be related to the dose of the racemate used clinically. The difference was greatest with the most active compounds and he suggested reasons for what has become known as 'Pfeiffer's rule'. In this short article Dick Barlow points out that there is a corollary to the rule - that the activity of the weaker enantiomer is determined by the activity of the more potent one - which is intuitively imporbable. With more examples and in a simpler situation, the picture is more complex and there are marked exceptions. The ideas behind Pfeiffer's rule overlook differences in molecular flexibility and there is a need for a revised model that takes entropy differences into account, particularly as recent developments in the elucidation of receptor structure are likely to revive interest in Pfeiffer's rule. PMID- 2333667 TI - MRI of the adrenal gland. AB - Current status of magnetic resonance imaging (MRI) of the adrenal gland is reviewed, and basic techniques and sensitivity of MRI for differentiating histologic lesions are also discussed. PMID- 2333668 TI - A renal cell carcinoma extending into the renal pelvis simulating transitional cell carcinoma. AB - A case of renal cell carcinoma with unusual extension is reported, in which the radiographic findings have a close resemblance to those of transitional cell carcinoma of the renal pelvis. We emphasize that it is occasionally difficult to draw a distinction between transitional cell carcinoma with renal invasion and renal cell carcinoma with renal pelvic extension even by computed tomography (CT) and angiography. PMID- 2333669 TI - Congenital ureteropelvic junction obstruction with calcified renal pelvis and superimposed spindle cell urothelial carcinoma. AB - A case of congenital ureteropelvic junction obstruction with calcification of the walls of the renal pelvis and with a superimposed urothelial tumor is described and illustrated. PMID- 2333670 TI - Retroperitoneal-pericardial fistula caused by a perinephric abscess. AB - A case of a perinephric abscess complicated by a fistulous tract leading to the pericardium is presented. We report herein on the conventional radiological findings. PMID- 2333671 TI - Aggressive angiomyxoma of pelvic soft tissue: CT appearance. AB - A case of aggressive angiomyxoma of pelvic tissue is described. The characteristic clinical presenting symptoms together with radiographic findings can be suggestive of this disease. Computed tomography (CT) clearly depicted a solid mass in the pelvis without invasion of visceral structures and reaching caudally into the perineal region. PMID- 2333672 TI - MR imaging of bladder neoplasms: correlation with pathologic staging. AB - This retrospective study describes the accuracy of magnetic resonance (MR) imaging in determination of local disease extent in 34 examinations performed for evaluation of primary or recurrent bladder carcinoma. The 34 examinations were carried out in 29 patients (17 men, 12 women, aged 34-89 years). All studies were followed within 30 days by surgical and pathologic evaluation. Images were interpreted by two radiologists unaware of clinical or pathologic findings. MR imaging staging conformed to the TNM system of the International Union Against Cancer (IUAC). Pathologic evaluation showed bladder neoplasms in all cases; three patients' pathologic specimens contained two or more histologic types of tumors. MR imaging staging of the depth of tumor invasion was correct in 85% of examinations. Sensitivity of MR imaging for detection of deep muscle invasion was 97%, specificity 83%, and accuracy 94%. Sensitivity of MR imaging for detection of extravesical tumor extension was 95%, specificity 100%, and accuracy 97%. Sensitivity for detection of pelvic lymph node metastases was 50%, specificity 100%, and accuracy 82%. Our population included many patients with locally advanced disease. This pattern reflects standards of clinical practice by which superficial lesions are staged and resected endoscopically, and deeply invasive tumors are imaged prior to radical surgery. PMID- 2333673 TI - Stress incontinence secondary to a vesicourethral fistula: case report. AB - A previously unreported case of vesicourethral fistula in a female is presented. Its possible etiology and recommendations are discussed. PMID- 2333674 TI - Ioversol for intravenous urography: a comparison study. AB - A new nonionic, low-osmolar iodinated contrast media, ioversol, was compared with another low-osmolar, nonionic contrast media, iohexol, in 80 patients undergoing intravenous urography. There were 40 patients in each contrast group. Patients were assessed for changes in vital signs, patient tolerance (heat and pain), and other adverse effects. Double-blind evaluation was also performed for comparison of the urogram image quality. There were no severe, life-threatening reactions for either contrast group. Ten patients (25%) receiving ioversol and seven (17.5%) receiving iohexol perceived body heat related to the injection of contrast material. Two patients (5%) in each group experienced mild nausea. Two patients (5%) of each group experienced noted unpleasant taste, and two patients (5%) of the iohexol group complained of headache. Vital signs remained stable without significant change in both groups, and image quality was considered equivalent. The results indicate that the two contrast agents are equivalent in image quality, safety, and incidence of adverse effects. PMID- 2333675 TI - Unilateral ureteral obstruction in a patient with acute leukemia. PMID- 2333676 TI - [Use of synchronized heifer-recipients in view of the effectiveness of embryo transfer in cattle]. AB - A possibility was investigated of using heifers prepared for embryo reception by i. m. double application of Oestrophan (Spofa) luteolytic preparation. After a clinical examination of ovaries and corpus luteum, out of the total number of 2894 animals synchronized for nonsurgical ipsilateral transfer in the D7 stage only 2038 (70.4%) recipients were used. Almost 30% (856) heifers were discarded from the role of recipients, mostly due to the functional disorders of the cyclic activity of ovaries manifesting themselves as luteal cysts (22.5%), cysts of corpus luteum (16.5%), small or young corpora lutea (12.7%), postovulation states (4.5%), and also as a high frequency of the follicular activity without the presence of corpus luteum (37.9%). The occurrence of follicular cysts (1.4%) and nonfunctional ovaries (2.8%) was considerably lower. The high number of discarded recipients which results, in the complex of causes, from qualitative nutritional disorders, husbandry and zoo-hygienic shortcomings and stress-inducing factors in the course of recipient selection and preparation, diminishes the transfer efficiency and considerably increases the claims for the numbers of recipient prepared for ovulation. In the conditions of our workplace where 10.6 to 12.8 transferable embryos are recorded from one successful superovulation and their survival is 65 to 68.6%, it will be necessary, at the present level of recipient discarding, to prepare 13.8 to 16.6 heifers per donor to make full use of the superovulation effect. PMID- 2333677 TI - [The effect of nutrition and technology on fertility in cows and the health of calves]. AB - The fertility of cows and health of calves are influenced by a number of factors, including the technological systems and quality of nutrition. The effect of nutrition was studied in two selected herds with different technological systems during 1986 to 1987. The feed rations were found to be non-standard, the nutrient ratios were not balanced, and the animals suffered from different stages of metabolic disorders. These disorders were worse in the H. large-capacity barn, equipped with modern technology, in comparison with the S. barn with traditional technology. The better reproduction data recorded in the S. barn, using the traditional technology, are ascribed to better organization of work, better feeding, and better care of the animals. The production of viable calves is the most vulnerable point in the reproduction process. Great reserves were found to exist in both the herds studied. The shortcomings suggest that knowledge of the factors and the causes of losses during the year seasons is a prerequisite for tracing the aetiology and taking effective measures, which in turn will influence the weaning. If fertility is to remain high, fertility disorders must be treated in time. As the analyses show, uterus diseases are diagnosed most frequently under farm conditions; their occurrence is associated with the hygiene of parturition and generally with hygiene in the barn. The set of recommendations to improve the reproduction process in the two herds influenced the economy of the farms. PMID- 2333678 TI - [Activity of mucosubstances and the goblet cell count in the large intestine of piglets infected with the coccidium, Isospora suis]. AB - In a group of conventional and gnotobiotic piglets experimentally infected with the Isospora suis coccidia the quantitative presence of acid and neutral mucous substances in the large intestine and the counts of goblet cells in the surface mucosa and in Lieberkuhnis crypts (in the following text called just the crypts) were investigated. In conventional piglets infected with the dose of 200,000 oocysts of I. suis coccidia the lowest content of acid mucous substances was recorded from the eighth to tenth day after infection (DAI). A decrease in the activity of neutral mucous substances was somewhat slower. The lowest count of goblet cells was found on DAI 9, especially on the surface mucosa (4.89 to 4.91 goblet cells per 10 enterocytes). There was observed no difference in the piglets infected the first and fifth day after parturition (DAP). Gnotobiotic piglets infected with the dose of 100,000 oocysts of I. suis coccidia on DAP 1 showed the lowest content of mucous substances in the large intestine from the ninth to tenth day after infection. Unlike the conventional piglets, in gnotobiotic piglets there was recorded a decrease in the content of acid and neutral mucous substances. The gnotobiotic piglets had the lowest counts of goblet cells in the surface mucosa (10:4.57) and in the crypts (10:7.71) on DAI 9. As to the quantitative proportions, in the conventional and gnotobiotic piglets neutral mucous substances prevailed on the other days (DAI 3-7 and DAI 11), similarly like on DAI 8. The results of this investigation revealed a functional disease of the large intestine in conventional and gnotobiotic piglets infected experimentally with the Isospora suis coccidia. PMID- 2333679 TI - [Changes in the biometry of the sex organs of sheep after estrus synchronization and superovulation in the breeding period]. AB - In twenty ewes of the Slovak Merino breed coming from a demonstration farm at Zemplinska Teplica, to the age of two-three years biometrical variations of the sex organs and overall follicular response to PMSG and PGF2 alpha administration were investigated in the autumn period (October-November). In the ewes of all groups the heat was synchronized by i. m. administration of PGF2 alpha (Oestrophan Spofa) at a dose of 125 micrograms in the interval of 11 days. On the ninth day the ewes of the second and fourth group were given 1000 i. u. of PMSG (Antex Leo, Denmark), the ewes of the third group 750 i. u. of PMSG. The ewes of the third and fourth group were administered at the same time 50,000 i. u. vitamin A (Axerophtol Spofa) (each group). The weight and dimensions of the sex organs were investigated. The results demonstrate that the administration of PMSG in the mating period increases significantly the weight of oviducts and horns of uterus in the ewes while there are no variations of the weight of the other sex organs and of their length, or it is lower than in the ewes of the control group. The overall follicular response was not influenced by the higher weight of ovaries. PMID- 2333680 TI - [An unusual occurrence of spinaliomas in schnauzers]. AB - This paper describes 17 cases of digital spinocellular carcinomas of the limbs of the schnauzer dogs (14 in males and 3 in females) which were diagnosed from July 1987 to the end of 1988. During comparison of the prevalence of these neoplasmas over the period 1975 to 1984, when 11 cases of spinaliomas were diagnosed in dogs, there is an uncommonly high and interesting incidence of these tumors in schnauzers. Spinaliomas were not diagnosed in other breeds and in other locations. We know of no other similar observation. The tumour had the appearance of a poorly mending wound or panaritium and they locally destroyed the digits of the affected individuals. Recurrence was observed once, metastases in lymphatic nodes or other tissues were not observed up to the present time. Histologically the tumors had the appearance of well differentiated spinocellular carcinomas with a fibro-producing and intensive inflammatory reaction. The sarcomatous appearance of the tumor parenchyma was sporadically observed. Lesions were indications for the amputation of the affected digits. As possible etiological factors the authors consider, besides traumatic influences of the overgrown claws, even hormonal and infectious influences. PMID- 2333681 TI - Evaluation of an interfragmentary compression system for the repair of equine femoral capital physeal fractures. AB - Femoral neck and proximal epiphyseal lengths were measured in 37 femurs from 19 cadaver foals that were 1 day to 12 months old to determine the applicability of a human interfragmentary compression system to equine femoral capital physeal fractures. Because components of the implant system are available only in fixed sizes, its use was possible in foals older than 5 weeks of age, but not in younger foals. The 135 degree angle plate conformed best to the equine femur. Femoral capital physeal fractures were created surgically and repaired with the implant system in three foals. Fracture stability was evident clinically and radiographically in all three foals until euthanasia at month 3. At necropsy, the treated femurs were 4, 8, and 27 mm shorter than their mates. Epiphyseal viability was verified in all three foals by tetracycline deposition and new appositional bone growth comparable with that in the contralateral control epiphyses. The treated capital physis was open but reduced in thickness in one foal, disorganized in one foal, and closed in one foal. Fixation by compression with the implant system resulted in stability sufficient for fracture healing and maintenance of epiphyseal viability, although it was associated with reduced longitudinal femoral growth. PMID- 2333682 TI - Surgical repair of tibial tuberosity avulsion fractures in four horses. AB - Four horses, 2 to 17 years old, were treated for unilateral avulsion fractures of the tibial tuberosity. Two horses were treated successfully with tension band wiring or plating in combination with lag screw fixation. One horse was euthanatized because of implant failure during recovery and one was euthanatized on day 11 because a longitudinal fracture of the tibial tuberosity occurred through the plane of the screws used for stabilization. PMID- 2333683 TI - A large frontonasal bone flap for sinus surgery in the horse. AB - A large frontonasal bone flap was created to treat diseases of the paranasal sinuses in 14 horses. The bone flap was made as wide as possible within the confines of the nasolacrimal duct so the floor of the frontal sinus and the dorsal and ventral conchae could be opened. These openings exposed the nasal passages, maxillary sinuses, and ventral conchal sinus thereby facilitating removal of diffuse and localized lesions from these sites. Diseases treated were ethmoid hematomas (4 horses), sinus cysts (5 horses), cryptococcal granuloma, osteoma, hemangiosarcoma, pus in the ventral conchal sinus, and periapical infection of a second molar. Four horses were euthanatized during or after surgery, one because of postsurgical pleuritis and pneumonia (horse with osteoma) and three because of their primary problems (cryptococcal granuloma, hemangiosarcoma, pus in the ventral conchal sinus). Skin suture abscesses that responded to treatment developed in four horses. Ten horses returned to their intended uses, the sinus flaps healed without blemish, and the original problems did not recur. The frontonasal flap technique provided greater access to all paranasal sinuses than methods described previously. PMID- 2333685 TI - Effects of left recurrent laryngeal neurectomy, prosthetic laryngoplasty, and subtotal arytenoidectomy on upper airway pressure during maximal exertion. AB - Upper airway pressure was measured with a nasotracheal catheter system and a portable pressure transducer in 10 normal horses during maximal exercise before and after left recurrent laryngeal neurectomy. Measurements were repeated 16 weeks after prosthetic laryngoplasty (5 horses) or subtotal arytenoidectomy (5 horses). During maximal exertion, prosthetic laryngoplasty was more effective than subtotal arytenoidectomy in reversing the increases in upper airway pressure that followed left recurrent laryngeal neurectomy. PMID- 2333684 TI - Local anesthetics and nuclear medical bone images of the equine fore limb. AB - The effects of two local anesthetic agents on the diagnostic quality of nuclear medical bone images (NMBIs) of distal parts of the equine fore limb were investigated. Local effects on bone uptake of technetium 99m methylene diphosphonate (99mTc-MDP) 4 and 24 hours after perineural and intraarticular injection of mepivacaine hydrochloride and bupivacaine hydrochloride were evaluated in the carpal and metacarpophalangeal regions of 12 horses and ponies. Neither mepivacaine hydrochloride nor bupivacaine hydrochloride significantly altered the diagnostic quality of the NMBIs. The injection and subsequent action of local anesthetics do not appear to influence local bone uptake of 99mTc-MDP significantly. PMID- 2333686 TI - Upper airway function during maximal exercise in horses with obstructive upper airway lesions. Effect of surgical treatment. AB - Upper airway pressure was measured during maximal exercise in 10 Thoroughbred racehorses with naturally occurring upper airway obstruction. Left laryngeal hemiplegia and arytenoid chondropathy resulted in substantial increases (30-40 cm H2O) in inspiratory upper airway pressure (Pl), whereas complicated aryepiglottic entrapment and subepiglottic cysts produced only modest increases (15 cm H2O) in Pl. Uncomplicated aryepiglottic entrapment and grade IV pharyngeal lymphoid hyperplasia produced only slight increases (3-5 cm H2O). In general, surgical procedures restored airway pressures to within normal limits. Subtotal arytenoidectomy improved but did not normalize airway pressures in horses with arytenoid chondropathy. Pharyngeal lymphoid hyperplasia appeared to have little effect on upper airway function. PMID- 2333687 TI - An open patch-graft technique for correction of pulmonic stenosis in the dog. AB - An open patch-graft technique for correction of pulmonic stenosis was performed in four dogs. A synthetic patch-graft was presutured to a partial-thickness incision in the right ventricular outflow tract and to the pulmonary artery along its cranial border. The pulmonary artery and right ventricle were incised during venous inflow occlusion, and dysplastic pulmonic valve leaflets were excised. The arteriotomy was closed by suturing the caudal margin of the incision to the patch graft. The entire procedure was performed during mild hypothermia (30 degrees - 32 degrees C). The mean circulatory arrest time was 5.5 +/- 0.2 minutes. The mean systolic pressure gradient across the pulmonic valve before surgery was 121 +/- 29 mm Hg; after surgery it was 9 +/- 2 mm Hg. PMID- 2333688 TI - Static strength evaluation of sacroiliac fracture-separation repairs. AB - The relative static strengths of seven fixation configurations for the repair of sacroiliac fracture-separations were determined. The fixation techniques were two 3.5 mm screws, one 4.5 mm screw, one 4.5 mm screw and a pin, two 4.5 mm screws, one 6.5 mm screw, one 6.5 mm screw and a pin, and two 6.5 mm screws. Each configuration was subjected to a torsional, a bending, and a shear disruptive force while the maximum load tolerated before failure was measured. Two screws were stronger than a single screw of similar size, two small screws were stronger than a single larger screw, and a reduction pin added no significant strength to a single screw repair. It was concluded that use of the largest screws possible will maximize the strength of a sacroiliac fracture-separation repair. PMID- 2333689 TI - Chronic otitis externa and otitis media treated by total ear canal ablation and ventral bulla osteotomy in thirteen dogs. AB - Ventral bulla osteotomy was combined with total ear canal ablation for the treatment of chronic otitis externa and otitis media in 13 dogs (14 ears) that had been refractory to medical and surgical treatments. Resolution of disease occurred in 11 dogs (12 ears). One dog with unilateral disease underwent a second operation before achieving a good result. One dog was euthanatized for persistent unilateral disease after three surgical procedures. The recurrence of disease in these two dogs (15%) was associated with remnants of ear canal integument within the osseous horizontal canal or tympanic bulla. Facial paralysis occurred in four dogs (31%) and there were no complications in eight dogs (62%). This technique shows no advantage over lateral bulla osteotomy combined with total ear canal ablation for the treatment of chronic otitis externa and otitis media. PMID- 2333690 TI - Hemodynamic effects of intravenous midazolam-xylazine-butorphanol in dogs. AB - The hemodynamic effects of a mixture of midazolam (1.0 mg/kg), xylazine (0.44 mg/kg), and butorphanol (0.1 mg/kg) were evaluated in six adult dogs. The dogs were anesthetized with isoflurane for instrumentation. As the dogs returned to consciousness, baseline values were recorded and the midazolam-xylazine butorphanol mixture and glycopyrrolate (0.01 mg/kg) were administered intravenously (IV). Hemodynamic data were recorded 3, 10, 20, 30, 40, 50, and 60 minutes after injection. Mean arterial pressure (AP), mean pulmonary arterial pressure (PAP), heart rate (HR), rate-pressure product (RPP), mean pulmonary capillary wedge pressure (PCWP), systemic vascular resistance (SVR), and right ventricular stroke work index (RVSWI) were increased significantly above baseline values. Cardiac output (CO), stroke volume (SV), cardiac index (CI), stroke index (SI), mean central venous pressure (CVP), and left ventricular stroke work index (LVSWI) were decreased significantly below baseline values. When administered IV at the dosages used in this study, midazolam-xylazine-butorphanol-glycopyrrolate induced profound acute alterations in several critical hemodynamic variables. PMID- 2333691 TI - Arthroscopic approaches and intraarticular anatomy of the equine elbow. AB - Periarticular anatomy and techniques for arthroscopic access to the equine elbow were studied in six joints from cadavers. Caudomedial and craniolateral approaches were evaluated subsequently in 11 anesthetized horses. The caudomedial approach was made between the flexor carpi radialis and flexor carpi ulnaris muscle bellies. Most of the caudal articular surfaces of the humeral condyles, the caudal perimeter of the radius, and the trochlear notch and portions of the anconeal process of the ulna could be identified. The voluminous caudal joint capsule cul-de-sac proximal to the anconeal process was readily entered. A 70 degree arthroscope allowed examination of more of the joint recesses and articular surfaces of the olecranon fossa than a 25 degree arthroscope. A second portal for intraarticular instrument manipulation was made caudal and slightly proximal to the arthroscope entry. Entry more proximal than the level of the radiohumeral articulation carried significant risk of damage to the ulnar nerve and collateral ulnar artery and vein. For examination of the cranial regions of the elbow, a craniolateral portal was established cranial to the lateral collateral ligament. An instrument portal was made through the muscle bellies of the extensor carpi radialis or common digital extensor muscles. The cranial articular surfaces of the humeral condyles were readily exposed by extension of the elbow. The weight-bearing articular surface of the radius could not be seen. Eight horses were euthanatized without recovery from anesthesia and the elbows were dissected for examination. Three horses were allowed to recover from anesthesia and were euthanatized on days 3, 30, and 60.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333692 TI - Questionnaires from the National Health Interview Survey, 1980-84. PMID- 2333693 TI - The West Indian Medical Journal. Past, present and future. PMID- 2333694 TI - Childhood pica. Some aspects of the clinical profile in Manchester, Jamaica. AB - The clinical profile of 108 children aged 1 1/2 years to 10 years who practised pica was compared to that of 50 non-pica patients aged 2 years to 10 years. Of the patients with pica, 85% were less than 5 years of age and 29% were aged 1 1/2 years to 2 years. The male to female ratio was 1:1.4. Ninety-two patients ingested dirt, 35 marl, 33 stone, 17 coal and 10 ashes. Twenty-two patients ingested multiple substances. Family history for pica was positive in 44 patients. Forty-six per cent of pica patients and 12% control patients had poor nutritional status (p less than 0.05). Ten per cent of pica patients were constipated while 26% had persistent diarrhoea. Intestinal parasites were identified in 70.3% of cases and were distributed as follows: Trichuris species 66%, Ascaris lumbricoides 26.6%, Giardia lamblia 17%, and mixed infestations 28.8%. Initial haemoglobin values were less than 8 gm/dl in 34.8% and 11 gm/dl or greater in 20.9% of pica patients compared with 12% and 56%, respectively, in control patients (p less than 0.05) It is concluded that, in our country, the children who practise pica are prone to malnutrition, anaemia, diarrhoea/constipation and worm infestation. Geophagia is most frequently involved and there is often a family history of pica. PMID- 2333695 TI - Leptospirosis in Barbados. A clinical study. AB - A 39-month clinical study of leptospirosis was undertaken at the Queen Elizabeth Hospital, Barbados. Eighty-eight patients had a confirmed diagnosis of the disease during the period. The major serogroups identified were autumnalis (including a new serovar bim), icterohaemorrhagiae, ballum and canicola. The majority of patients presented with jaundice (95%,) anorexia and headaches (85%), fever (76%) and conjunctival suffusion (54%). While abnormal creatinine levels were seen in 49% of patients on admission, only 16% were judged to have had renal failure. The urine to plasma urea ratio showed high sensitivity and specificity in the diagnosis of pre-renal azotemia. Cardiac arrhythmias and myocarditis occurred in 18% of patients and pericarditis in 6%. An elevated serum amylase was found in 65% of cases. The bilirubin level took 5.5 weeks to return to normal. Thrombocytopenia was shown not to be due to a disseminated intravascular coagulation, and a randomised trial of high dose penicillin did not reveal any benefit to jaundiced patients. The overall mortality during the study was 5.7%. PMID- 2333696 TI - Testicular and paratesticular tumours at the University Hospital of the West Indies. AB - A review of tumours of the testis and paratesticular region diagnosed at the University Hospital of the West Indies over a 30-year period revealed 14 of the former and 22 of the latter. The testicular tumours were all malignant, with 50 per cent of them being germ-cell neoplasms. Seventeen of the 22 paratesticular tumours, (77.3%) were benign. The histological types, racial incidence and possible aetiological factors are discussed and compared with the findings of other series. PMID- 2333697 TI - The epidemiology and management of patients with hydatidiform mole. AB - The epidemiology, clinical features and method of evacuating the uterus were reviewed in 30 patients with hydatidiform mole. The incidence was greatest in patients with blood group O and among young East Indians. There was no seasonal variation nor was there any progression to choriocarcinoma. Only one partial mole and one invasive mole were encountered. Evacuation was achieved chiefly by suction curettage and concomitant augmentation with a Syntocinon infusion. PMID- 2333698 TI - Malignant carcinoid syndrome. Failure of anti-oestrogenic therapy. AB - A pre-menopausal patient with a six-year history of symptoms of the metastatic carcinoid syndrome leading to progressively worsening carcinoid heart disease is described. The failure of anti-oestrogenic therapy (sequential bilateral oophorectomy and Tamoxifen therapy) to halt progression of disease was documented. Death resulted from right ventricular failure associated with pulmonary and tricuspid valvular disease. PMID- 2333699 TI - Meckel-Gruber syndrome. A lethal combination of abnormalities. AB - We herein describe two cases of Meckel-Gruber Syndrome identified in stillborn infants. Both had all three elements of the classical triad, namely, occipital encephalocele, renal cystic dysplasia and post-axial polydactyly. In addition, many of the other well-known accompanying abnormalities were present. Awareness of this entity in this region is important because of its high risk of recurrence in subsequent pregnancies. PMID- 2333700 TI - Blastocystis hominis in two children of one family. AB - Two apparently healthy children from the same family were found to have moderate to heavy Blastocystis hominis in their stool samples whilst being investigated for intestinal symptoms: sporadic, painless, rectal bleeding in one and persistent diarrhoea in the other. After treatment with metronidazole, they had no further signs, and stool samples became negative. Eighteen months later, both were asymptomatic, and stool samples continued to be negative for the parasite. PMID- 2333702 TI - Physicians as role models in society. PMID- 2333701 TI - Serum antibodies to Giardia lamblia by age in populations in Colorado and Thailand. AB - We measured levels of antibodies to Giardia lamblia by age in serum specimens from persons in Denver, Colorado, and Soongnern, Thailand. Serum levels of immunoglobulin (Ig) G, IgM, and IgA G lamblia-specific antibodies measured by enzyme-linked immunosorbent assay increased substantially during childhood in both geographic areas, although children in Soongnern showed significantly higher mean levels of each antibody class (P less than .05). After adolescence, levels of G lamblia-specific IgM fell steadily with age in both populations. In contrast, specific IgA levels remained elevated throughout life among the Thai but decreased to low levels among adults in Denver. Similarly, rates of carriage of G lamblia were high among children aged 1 to 4 years in Denver and Soongnern (14.3% versus 26.5%, respectively) but were much lower among adults in Denver (0% versus 14%; P less than .01). These data suggest that levels of G lamblia specific IgM may reflect exposure to the parasite early in life in both areas. Levels of parasite-specific IgA may reflect recurrent exposure to G lamblia in Soongnern, where G lamblia is endemic, but less frequent exposure to the parasite in Denver, where exposure is often episodic. PMID- 2333703 TI - Biological significance of Giardia-specific antibodies. PMID- 2333704 TI - Successful medical treatment of listerial brain abscess. PMID- 2333705 TI - Association of spontaneous pneumomediastinum with substance abuse. PMID- 2333706 TI - Evaluation of hematuria in adults. PMID- 2333707 TI - Malpractice litigation as a factor in choosing a medical specialty. AB - Although many factors have been identified as influencing specialty choice, there has been no research focusing on the effects of the current climate of medical practice, including litigation. Our study examines medical students' and residents' awareness of the malpractice litigation environment and their reasons for choosing a specialty that is at either high or low risk for malpractice suits. Longitudinal data showed that students continued to choose high-risk specialties (40%) even though they perceived problems in the current climate of litigation. Among the reasons for their choices were enjoyment and being able to practice in a procedure-oriented specialty that is effective in its mode of treatment. Those who chose low-risk specialties (60%) rated as important the variety of diseases seen and the opportunity to know patients well. Issues related to the malpractice climate were important only to those who switched from a high- to a low-risk specialty. These findings have implications for professional staffing needs. PMID- 2333708 TI - A simplified screening test for the diagnosis of allergy. AB - The Quidel allergy screen is a relatively rapid (less than 2 hours) multiallergen dipstick method for detecting specific immunoglobin E antibodies in serum. It was developed to answer the need of primary physician nonspecialists in allergy for a convenient in-office screening test for diagnosing allergy. The new test was evaluated against the benchmark diagnostic skin tests and the radioallergosorbent serologic tests for sensitivity, specificity, accuracy, and technical feasibility in an office setting. It was found that while the Quidel allergy screen lacks the specificity of the standard tests, its overall sensitivity, as defined by the percentage of patients with positive skin reactions who also tested positive with the Quidel screen (68%), its ease of use, and its rapidity warrant its consideration as a screening tool for confirming a possible case of allergy. PMID- 2333709 TI - The future of family practice training in California. AB - Although the number of physicians in California has doubled since 1963, the number of family and general practice physicians has declined. The ratio of office-based primary care physicians to population has also decreased. Graduate medical education is funded largely from patient care revenues, but the low rate of reimbursement for ambulatory care makes training in primary care specialties especially dependent on public support. Medicare, the Veterans Administration, and the University of California provide more than $325 million a year in support of graduate medical education in California. Federal and state grant programs provide $5 million a year for family physician training in the state, but appropriations to these programs have been reduced in real terms. California family practice residencies are disproportionately located at county hospitals, where funding shortfalls make them especially vulnerable to cuts in grant programs. Additional resources will be needed if more family physicians are to be trained. PMID- 2333710 TI - Metabolic fate of indometacin farnesil, a prodrug of indomethacin: characteristic biotransformation of indometacin farnesil in rats. AB - 1. Hydrolysis of indometacin farnesil (IMF), a farnesyl ester of indomethacin, was higher in plasma and pancreatic juice than in liver and kidney homogenates of rats. Plasma hydrolytic activity was extremely low in beagle dog, monkey and human. 2. Orally administered 14C-IMF was absorbed mainly via the throacic lymph duct and distributed into tissues such as liver, adrenal and spleen as the unchanged from; the 14C in rat plasma was present mainly as indomethacin released from IMF. 3. The concentration ratios of indomethacin in carrageenin-induced inflamed paw to blood after 14C-IMF administration were significantly greater than those after 14C-indomethacin dosing. 4. These results indicate that absorbed IMF might be transported as the unchanged drug into tissues, including the site of inflammation and then hydrolysed to indomethacin in the tissues. PMID- 2333711 TI - Bioavailability, disposition and pharmacokinetics of 14C-ormetoprim in rainbow trout (Salmo gairdneri). AB - 1. Uptake, bioavailability, tissue disposition, and elimination of 14C were examined in rainbow trout following intravascular and per os dosing of 14C ormetoprim (8 mg/kg). 2. Plasma clearance was rapid following a single i.v. dose (t1/2 alpha = 0.54 h, t1/2 beta = 17.5 h) with an apparent volume of distribution (Vss) of 4.85 l/kg. An increase in both t1/2 alpha (0.67 h) and t1/2 beta (36.7 h) was seen following multiple i.v. doses (steady state). 3. Oral dispositional studies revealed the highest concentration of OMP in bile, kidney and liver, indicating significant renal and hepatic extraction. Significant OMP residues were seen in skin (0.90 p.p.m.) and muscle (0.15 p.p.m.) at 38 days. 4. Peak absorption time of orally administered OMP was 12 h with an apparent bioavailability of 87%. 5. Intravascularly administered OMP was 33% and 31% protein-bound at 1 and 6 h respectively, and binding was non-specific and non saturable by Scatchard analysis. PMID- 2333712 TI - The stereoselectivity of 1,2-phenylethanediol and mandelic acid metabolism and disposition in the rat. AB - 1. The steps involved in determining the chirality of the mandelic acid excreted by rats after administration of ethylbenzene and styrene were investigated by studying the fate of racemic, (R)- and (s)1,2-phenylethanediol, a precursor of mandelic acid. These investigations indicate the occurrence of two alternative routes of metabolism for 1,2-phenylethanediol, one involving retention of configuration and the other resulting in the loss of the chiral centre. 2. The stereoselectivity of the disposition of mandelic acid was investigated; rats were dosed with mandelic acid either as the racemate or as the individual enantiomers, G.1.c.-mass spectrometry and h.p.l.c. were used to determine the enantiomers of mandelic acid. 3. There were at least two routes by which mandelic acid could be metabolized and/or excreted; there is a stereoselective pathway in rat for (s) mandelic acid, which gives rise to phenylglyoxylic acid. 4. The chiral inversion of (s)-mandelic acid to (R)-mandelic acid is reported; although this has been observed in bacteria it has not previously been observed in mammals. 5. The extent to which mandelic acid is metabolized to phenylglyoxylic acid is dependent on the enantiomeric composition of the mandelic acid administered. There is no evidence to indicate significant ketone-alcohol conversion, that is phenylglyoxylic acid is not significantly reduced to mandelic acid in vivo. PMID- 2333713 TI - Aspirin acetylates the tricyclic antidepressant amoxapine spontaneously to N acetylamoxapine in vitro and in vivo. AB - 1. N-Acetylamoxapine is formed nonenzymically in vitro, and in mice, from amoxapine, a tricyclic antidepressant, and aspirin. 2. Formation of acetylamoxapine from amoxapine and aspirin in vitro was maximal at pH 5.0 since this pH optimized reactant solubilities as well as decreasing aspirin hydrolysis. 3. Formation of aceylamoxapine from amoxapine and aspirin in mouse stomachs was rapid, and the pH study indicates that the intestinal pH would favour formation even more. 4. Acetylamoxapine administered to mice produced the same CNS-related signs, leading to death, as with amoxapine, but much larger doses and longer time periods were required to elicit these effects. As brain and liver levels of amoxapine in animals dying from acetylamoxapine administration were less than half those found in animals given lethal doses of amoxapine, the toxicity in mice of acetylamoxapine may not be due solely to deacetylation of acetylamoxapine to the parent compound. PMID- 2333714 TI - Identification of glucose conjugates as major urinary metabolites of cannabidiol in the dog. AB - 1. Three dogs were treated i.v. with cannabidiol (CBD) and urine collected at intervals to 30 h. 2. Metabolites were extracted, converted into trimethylsilyl (TMS) derivatives and examined by g.l.c.-mass spectrometry. 3. The major metabolites excreted at early times were identified as the phenol glucosides of 4"-hydroxy-CBD, 5"-hydroxy-CBD and 6-oxo-CBD. 4. These three oxidized metabolites were not found unconjugated, and none of the free oxidized metabolites in urine were found conjugated with glucose. 5. The conjugates were hydrolysed by beta glucuronidase Type HP-2 from Helix pomatia and acid phosphatase but not by beta glucuronidase Type VII from E. coli. Differential reactivity towards alpha- and beta-glucosidase indicated that they possessed the beta-configuration. PMID- 2333715 TI - Metabolism of metronidazole and antipyrine in hepatocytes isolated from mouse and rat. AB - 1. In order to study species-related differences and select a model for the human metabolism of metronidazole and antipyrine, the Michaelis-Menten kinetics of metabolite formation from the two compounds were investigated in freshly isolated mouse and rat hepatocytes. 2. The average Km values for the formation of the major metronidazole metabolites ranged from 0.6 to 3 mM. The intrinsic clearance values (Vmax/Km) of metronidazole to the acetic acid, hydroxy and glucuronide metabolites were 58 (36-125) and 21 (12-28; P less than 0.05), 156 (63-263) and 36 (19-56; P less than 0.05), and 269 (102-452) and 500 (389-1616; P less than 0.05) nl/min per 10(6) hepatocytes, for mouse and rat, respectively (median with range, n = 6). 3. The average Km values for the formation of antipyrine metabolites ranged from 2 to 10 mM. The intrinsic clearance values for production of 3-hydroxymethyl-, nor- and 4-hydroxyantipyrine were 232 (43-519) and 487 (296 793; P less than 0.05), 594 (168-813) and 93 (55-180; P less than 0.05), and 118 (23-505) and 239 (134-501; P greater than 0.05) nl/min per 10(6) hepatocytes, for mouse and rat, respectively (median with range, n = 6). 4. The results demonstrate that metronidazole and antipyrine are metabolized with quantitative, but not qualitative, differences in isolated hepatocytes from mice and rats. Neither species provided an ideal model for the human metabolism of the two compounds. PMID- 2333716 TI - Human biliary metabolites of isotretinoin: identification, quantification, synthesis, and biological activity. AB - 1. The metabolites of isotretinoin (13-cis-retinoic acid, Accutane) were investigated in the bile of two patients with biliary T-tube drainage after administration of a single, oral, 80-mg dose of 14C-isotretinoin. Radioactivity measurements showed that the two patients excreted 22.7 and 17.1% of the dose in their bile in 4 days. 2. The two major drug-related components in the bile were identified as the glucuronide conjugates of 4-oxo-isotretinoin and 16-hydroxy isotretinoin. Two minor components were identified as the glucuronide conjugates of isotretinoin and 18-hydroxy-isotretinoin. 3. H.p.l.c. analyses of Glusulase treated bile samples indicated that the glucuronides of isotretinoin and the two major metabolites accounted for about 48% and 44% of the total radioactivity in the bile of the two patients. 4. Racemic 16-hydroxy-isotretinoin was synthesized and evaluated for its effect on human sebocytes in vitro. This metabolite and the other major metabolites of isotretinoin were less active than isotretinoin in inhibiting the proliferation of the sebocytes. PMID- 2333717 TI - The metabolism of eugenol in man. AB - 1. The metabolism of eugenol (4-hydroxy-3-methoxy-allylbenzene) was investigated in male and female healthy volunteers. It was rapidly absorbed and metabolized after oral administration and was almost completely excreted in the urine within 24 h. Unmetabolized eugenol excreted in urine amounted to less than 0.1% of the dose. 2. The urine contained conjugates of eugenol and of nine metabolites. The structures of these metabolites, elucidated using g.l.c.-mass spectrometry, and by comparison with synthetic reference compounds, were identified as: eugenol, 4 hydroxy-3-methoxyphenyl-propane, cis- and trans-isoeugenol, 3-(4-hydroxy-3 methoxyphenyl)-propylene-1,2-oxide, 3-(4-hydroxy-3-methoxyphenyl)-propane-1,2 diol, and 3-(4-hydroxy-3-methoxyphenyl)-propionic acid. 3. The structures of the following metabolites were tentatively deduced from mass spectra only, as reference compounds were not available: 3-hydroxy-3-(4-hydroxy-3-methoxyphenyl) allylbenzene, 3-(6?-mercapto-4-hydroxy-3-methoxyphenyl)-propane, and 2-hydroxy-3 (4-hydroxy-3-methoxyphenyl)-propionic acid. 4. The amounts of the individual metabolites excreted were determined by g.l.c. Some 95% of the dose was recovered in the urine, most of which (greater than 99%) consisted of phenolic conjugates; 50% of the conjugated metabolites were eugenol-glucuronide and sulphate. Other metabolic routes observed were the epoxide-diol pathway, synthesis of a thiophenol and of a substituted propionic acid, allylic oxidation, and migration of the double bond. PMID- 2333718 TI - Characterization of guinea pigs adapted to differently high vitamin C supplies. 1. Blood-levels of cholesterol, glucose, triacylglycerides and hemoglobin. AB - Guinea pigs adapted (6-10 weeks) to low supply with vitamin C in the food show the tendency to increased levels of cholesterol and triacylglycerides in the blood and to decreased levels of hemoglobin and of glucose in comparison to guinea pigs adapted to medium and high supply. PMID- 2333719 TI - [The effect of a supplement of citric acid on the bioavailability of zinc from corn germ]. AB - The purpose of this 2 factorial designed study was to investigate the influence of citric acid on the availability of zinc from diets containing 140 g corn germs as a native phytate source (0.5% phytate in diet). Growing male rats with an average initial weight of 42 g were divided into 8 groups of 8 animals each. After a 7 d depletion period (2.4 micrograms Zn/g diet) the animals were fed ad libitum for 21 d a diet on the basis of egg white solid and corn germs. The diets were supplemented with zinc in order to obtain phytate:zinc molar ratios of 31, 20, 14, and 0 (control without corn germs, 11 micrograms Zn/g diet). Each diet was fed with and without a supplementation of 1% citric acid. A phytate:Zn molar ratio of 31:1 resulted in typical symptoms of zinc-deficiency like anorexia, alopecia and a significant depression of growth. These effects were apparently reduced by citric acid. The zinc concentration in serum and organs followed the graded levels of phytate:zinc molar ratios. Primary significant effects of the phytate:Zn molar ratio but also effects of citric acid and interactions between the 2 factors phytate:Zn and citric acid could be detected. Only total liver zinc but not liver zinc based on fresh matter was affected by the phytate:Zn molar ratio. In serum and tissues the activity of alkaline phosphatase showed a significant response to the phytate:zinc molar ratio. Furthermore the supplementation with citric acid increased the femur alkaline phosphatase and slightly reduced it in the liver. The concentrations of metallothionein in liver duodenum, jejunum and ileum were significantly affected by the phytate:Zn molar ratio. PMID- 2333721 TI - [Effect of emotions on the choice of goals and actions]. AB - The present paper concerns the influence negative emotions exert on motivational processes, i.e., on the selection of goals and corresponding actions. It is assumed that, in a negative emotional state, the goal to overcome this negative mood state takes precedence over the goal to succeed in a nonemotional task. Correspondingly, emotion-related activities should be preferred to task-related ones. In order to test this assumption, subjects in a negative and a neutral emotional state were given a series of activities, some suited for coping, some suited for task fulfilment. They were instructed to name (Experiment I) or to carry out (Experiment II) those activities they preferred at the very moment and to give a short reason for each choice. Results showed that subjects in a negative mood compared to those of the neutral control group were less occupied with the nonemotional task, but instead more frequently chose emotion-related activities with the explicit reason that these activities served to overcome their negative emotions. PMID- 2333720 TI - Determination of thiamine (vitamin B1) in maternal blood during normal pregnancies and pregnancies with intrauterine growth retardation. AB - The concentration of thiamine (vitamin B1) was measured in blood cells and plasma from mothers with normal pregnancy and from mothers whose pregnancy was complicated by intrauterine growth retardation (IUGR). Thiamine concentrations were estimated by the thiochrome method using HPLC separation and fluorimetric detection according to Weber et al. (2). During normal pregnancies the thiamine values in blood cells fall in the 28th to the 39th week of gestation from 230 nmol/l to 170 nmol/l. In cases with severe IUGR there is only a slight decrease in the thiamine levels from 140 nmol/l in the 30th week of gestation to a level of 130 nmol/l in the 39th week of gestation. During this period the thiamine values in plasma remain constant. To compare the thiamine concentrations in normal pregnancies and in those with IUGR we separated the thiamine values in a group from 28/0 to 34/6 and one from 35/0 to 39/6 weeks of gestation. In both groups mothers with normal pregnancy had significantly higher thiamine levels in the blood cells than mothers whose pregnancy was complicated by IUGR (p = 0.0001 and p = 0.0005). However, the thiamine values in plasma were not significantly different in normal pregnancies and pregnancies with IUGR. The results indicate that maternal thiamine deficiency might be one cause of IUGR. PMID- 2333722 TI - [Coping in imprisonment: a study of the sequelae of the arrest of adolescents]. AB - A coping model for the assessment of the effect of prison life is proposed. On this basis, previous findings of such effects can be interpreted as coping patterns learned under the specific conditions. Within this theoretical framework, the individual perceptions of the inmates regarding the atmosphere in a therapeutically oriented department and in three conventional settings of the same prison are compared. Furthermore, differences in their social attitudes and self-descriptions are assessed. A total of 108 juvenile prisoners filled out a multidimensional atmosphere scale for correction institutions and a multidimensional personality inventory for prisoners. All atmosphere dimensions of the group of prisoners in the therapeutically oriented setting differed significantly from the other three. Furthermore, the inmates of the therapeutic division showed less aggressive and negative attitudes than those of the other divisions. Other personality scales showed no significant differences. From these results it is concluded that the effects of prison life can be mitigated in a setting that provides the inmates with more opportunities to develop adequate coping behavior than a conventional prison environment does. PMID- 2333723 TI - [The anticipatory potential (contingent negative variation) as an indicator of neuronal information processing in relation to changes in slow potentials in the EEG]. AB - The aim of this study was to investigate the interaction between spontaneous Slow Potential Shifts (SPSs) and the probability effect on CNV amplitudes. Fifteen right-handed volunteers participated in this experiment. The presentation of the stimuli was triggered by spontaneous SPSs (duration: 2 seconds, mean-amplitude: 10 microV) in the EEG signal at Cz. Thus, two different S1s (S1a: 1500 Hz, S1b: 2000 Hz) were presented in a random order with a fixed probability of occurrence of 0.8 for S1a and 0.2 for S1b. Each S1 was followed by a light stimulus (S2) with a constant ISI of 4 seconds. According to the cue, the subjects had to push the left (S1a) or the right (S1b) response button as fast as possible with their right index finger. The order of the 4 experimental conditions (stimulus presentation triggered by negative or positive shifts and recording of negative or positive shifts without any stimuli) in which each subject participated was balanced across subjects. Several significant effects could be found by means of a two-way ANOVA for repeated measures (condition x recording site): Negative shifts were accompanied by smaller CNVs as well as PINVs (resolution deficits) at all recording sites; the probability effect was found to be significant in the positive shift condition at F3, F4, and Cz, but not in the negative shift condition except at Cz for the E-wave. CNVs triggered by negative shifts only showed a significant correlation (-.55) with reaction time. These results together favor a two-component model suggesting that SPSs, spontaneous and evoked, are largely generated by glia depolarization, which is evoked by but outlasts neuronal activity. PMID- 2333724 TI - [The behavior of fecal coliforms, enterococci and salmonellae in the agricultural use of sludge from purification plants]. AB - Considering especially the duration of survival of faecal-coliforms, enterococci and salmonellae the behaviour on plants and in soil were investigated after the treatment with sludge. From the epidemiological point of view the plants and soils were not dangerous after having treated them with sludge for nearly six months. Conclusions for the practical use in agriculture were drawn. PMID- 2333725 TI - [Hypokalemia with rhabdomyolysis secondary to chronic small bowel obstruction]. AB - Rhabdomyolysis, secondary to chronic small bowel obstruction. The authors report the case of a 48-year old man, who developed rhabdomyolysis based only upon hypokalemia secondary to a chronic gastro-intestinal disorder (chronic obstruction of the small bowel). They would like to point out that despite the rare occurrence of rhabdomyolysis associated with hypokalemia, this pathological condition cannot be underestimated. Complaints of acute myalgia and general muscle weakness are characteristic. Early recognition of this syndrome is mandatory because myoglobinuria could provoke acute renal failure with eventual fatal outcome. PMID- 2333726 TI - [Implantation technic and maintenance of a Hickman catheter for hemodialysis]. AB - Description of the technique of insertion of the Hickman catheter for hemodialysis based on 110 operations. Absolute prerequisites for correct functioning are: 1) Fluoroscopic control of the localization of this device in the superior vena cava and 2) Checking if adequate flow can be obtained. PMID- 2333727 TI - Preclinical and clinical care of extremity lesions in polytraumatized patients. AB - The first and principal aim of the preclinical care of polytraumatized patients is preserving life through the restoration of respiration and circulation. Following this, the external hemorrhages should be treated. Early reduction of closed and open fractures relieves the pressure on the skin and surrounding soft tissues and prevents secondary transport-damage. Immobilization of the fractures, together with the proximal and the distal joints in a pneumatic splint, is carried out before transport. During the clinical phase, the operative stabilization of the fractures follows reanimation and life-saving operations. Primary treatment is performed as far as possible, because it reduces late death due to sepsis and multiorgan failure. In case of several fractures, an order of treatment is set up: fractures with an arterial lesion, second or third-degree open fractures and fractures with an impending compartment syndrome are the most urgent. The principles of fracture treatment in elective surgery are also valid for emergency osteosynthesis, but the choice of the fixation-device can be different. The external fixation is the first-choice treatment for fractures of the lower leg, while plate osteosynthesis is preferred for femur and humerus. PMID- 2333728 TI - [External femoral hernia]. PMID- 2333729 TI - Combined cervical and left parasternal mediastinoscopy for pre-operative staging of left upper lobe lung cancer. AB - Since exploratory thoracotomy, incomplete and palliative resection do not in effect prolong life expectancy, it is essential to determine the operability of a lung tumor as accurately as possible. Cervical mediastinoscopy has dropped the percentage of exploratory thoracotomy considerably. However, the lymph nodes in the periaortic region cannot be reached at cervical mediastinoscopy and these form an important lymph drainage pathway for the left upper lobe. The periaortic lymph nodes can be explored by left parasternal mediastinoscopy. In the present study we investigate the value of combined cervical and left parasternal mediastinoscopy in all patients with a clinically operable central lung cancer in the left upper lobe, and in patients with a peripheral cancer of the left upper lobe, when the tumor histology is unfavourable, or when there is suspicion of invasion of the surrounding organs. In the retrospective group, we found metastases at cervical mediastinoscopy in 12.9% of the patients with a tumor of the left upper lobe. In the prospective group, we found metastases at cervical mediastinoscopy, in 41.9% of the patients with a tumor of the left upper lobe. All the patients with a positive mediastinoscopy were excluded from operation. In those cases the lymph nodes were involved, or at multiple localizations, or at one localization extranodulary. The number of exploratory thoracotomies dropped in the prospective period and the resectability increased from 79.4% to 96.5% for the left upper lobe. These data point to the reliability of left parasternal mediastinoscopy combined with the cervical mediastinoscopy in the assessment of the operability of the left upper lobe lung cancer, in order to avoid unnecessary thoracotomies. PMID- 2333730 TI - Radioiodine therapy in voluminous multinodular non-toxic goitre. AB - Large doses of radioiodine were administered since 1969 to 15 euthyroid patients with compressive voluminous goitres. A decrease in goitre size was observed in all patients (between 15 and 63%, average 39%). Maximal effect on goitre size was attained rapidly, partially already after less than one year and was almost maximal after 24 to 30 months. No significant local adverse reactions were observed; no patient required steroid administration. Hypothyroidism followed radioiodine administration in 30% of the patients after 2 years; after 8 years, all those who had survived were hypothyroid, requiring substitution therapy. In all patients there was a marked improvement in compression symptoms. The use of radioactive iodine therapy constitutes an alternative to surgery in selected patients with large compressive goitres in whom surgery is contraindicated because of age or other medical conditions. PMID- 2333731 TI - Cell metabolic activity in acromegaly: a microcalorimetric study of lymphocyte metabolism. AB - A discrepancy between the clinical impression of disease activity and basal serum levels of growth hormone is often seen in patients with acromegaly. A slightly better relation has been found to serum levels of IGF-I, but a technique for evaluation of cell metabolic activity in this disease is still missing. For this purpose we used microcalorimetry to determine heat production rate in lymphocytes from 15 patients with acromegaly. The mean heat production rate was 2.90 +/- 0.15 pW/cell, significantly higher than in 13 healthy subjects, 2.31 +/- 0.12 pW/cell (p less than 0.01). Heat production rates did not correlate significantly with basal growth hormone levels, but increased, in a statistically significant manner (p less than 0.001), in parallel with the score index used to evaluate the clinical activity of the disease. Using the technique of microcalorimetry we could thus demonstrate an increased metabolic activity at a cellular level in patients with acromegaly, a finding that is in accordance with the view that an increased cell metabolic activity is a component of the disease process in acromegaly. PMID- 2333732 TI - Pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone enanthate in non-human primates. AB - The pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone-enanthate were compared in orchidectomized cynomolgus monkeys (Macaca fascicularis) and in intact GnRH agonist-suppressed rhesus monkeys (Macaca mulatta). Following a single im injection of 32.8 mg testosterone enanthate or 32.7 mg dihydrotestosterone-enanthate, i.e. 23.6 mg of pure steroid, in the orchidectomized cynomolgus monkeys, serum testosterone and dihydrotestosterone levels rose to 400 and 800% of baseline, respectively, within 24 h. Androgen levels remained in that range for 3-5 days followed by a continuous decline until baseline values were attained after 4-5 weeks. The areas under the testosterone- and dihydrotestosterone-curves did not differ significantly 2290 +/- 340 (dihydrotestosterone-enanthate) vs 2920 +/- 485 (testosterone-enanthate) suggesting that similar amounts of steroid had been released from the respective ester preparation. Mean half-life estimates of the terminal elimination phase were 4 and 7 days for testosterone-enanthate and dihydrotestosterone-enanthate, respectively. In a second experiment rhesus monkeys received, at 4-weekly intervals, sc implantation of a biodegradable polylactic:polyglycolide rod loaded with the GnRH agonist buserelin. The last injection was given during week 20. GnRH agonist treatment suppressed serum bioactive LH, testosterone and dihydrotestosterone levels, testicular size, sperm production, and seminal carnitine content. The ejaculatory response to electrostimulation and the masturbatory behaviour were abolished. Testosterone or dihydrotestosterone injections at the same doses as above were given in week 10, 14, 17 and 20 of GnRH agonist treatment. Serum testosterone and dihydrotestosterone levels were stimulated 9- and 4-fold, respectively. Mean half life estimates for testosterone-enanthate and dihydrotestosterone were 5 and 7 days, respectively. Both ester preparations completely restored the ejaculatory response, ejaculate size, masturbatory behaviour, and seminal carnitine levels. In conclusion, androgen substitution with dihydrotestosterone-enanthate, in equivalent doses, is as effective as testosterone-enanthate in restoring reproductive functions in hypogonadal monkeys. PMID- 2333733 TI - Polyglandular autoimmune syndrome type II in patients with idiopathic Addison's disease. AB - The frequency of polyglandular autoimmune syndrome Type II, (idiopathic or autoimmune Addison's disease associated with autoimmune thyroid disease, and/or insulin-dependent diabetes mellitus), was retrospectively investigated in 44 patients (26 females and 18 males) with idiopathic Addison's disease (median age at onset 32.5 years, range 8-62; median observation time 17 years, range 0.5-41) evaluated between 1966 and 1988 in the Department of Endocrinology, General Hospital, Malmo. Twenty-two patients (16 females and 6 males) fulfilled the criteria for polyglandular autoimmune syndrome Type II and of these 16 had autoimmune thyroid disease and 9 insulin-dependent diabetes mellitus. In 7 of 9 patients insulin-dependent diabetes mellitus developed prior to Addison's disease, whereas autoimmune thyroid disease was diagnosed before as well as after Addison's disease and with a similar age distribution as Addison's disease. In conclusion, the present study indicates that polyglandular autoimmune syndrome Type II occurs in about 50% of patients with idiopathic Addison's disease and that autoimmune thyroid disease is more common than insulin-dependent diabetes mellitus in these patients. The present study also indicates that insulin dependent diabetes mellitus precedes Addison's disease in a majority of these patients and usually develops at a young age, whereas autoimmune thyroid disease precedes as well as succeeds Addison's disease and occurs at all ages in these patients. PMID- 2333734 TI - Effects of D-glucose and beta-hydroxybutyric acid on the in vitro development of (pre)chondrocytes from embryos of normal and diabetic rats. AB - In order to elucidate cellular mechanisms causing skeletal malformations in offspring of diabetic rats we studied the incorporation of thymidine and sulphate into embryonic (pre)chondrocytes exposed to increased levels of D-glucose and beta-hydroxybutyric acid for six days in vitro. The (pre)chondrocytes were prepared from embryos of normal or diabetic rats of a malformation-prone strain or from embryos of normal rats of a non-malformation-prone strain. Diabetic female rats of the former strain are known to produce a high proportion of offspring with mandibular and lumbosacral malformations. Increased beta hydroxybutyric acid caused decreased thymidine incorporation in all types of chondrocytes, and decreased sulphate incorporation in limb bud cells from embryos of normal rats from both strains. Elevated D-glucose levels yielded a slight decrease in thymidine incorporation in mandibular arch cells from embryos of normal rats of the malformation-prone strain, and a marked decrease of both sulphate and thymidine incorporation in mandibular arch cells from embryos of diabetic rats of this strain. The observations suggest that elevated levels of D glucose or beta-hydroxybutyric acid are able to inhibit the differentiation and growth of (pre)-chondrocytes and illustrate a selective sensitivity of mandibular arch (pre)chondrocytes to a diabetic environment. The data are compatible with the view that both D-glucose and beta-hydroxybutyric acid may cause aberrations in the development of rat mandibular arch chondrocytes, suggesting a role for these compounds in diabetic teratogenesis. PMID- 2333735 TI - Influence of neurohypophysectomy on the renal actions of aldosterone in the adrenalectomized rat. AB - The influence of aldosterone administration on urine flow, Na+ and K+ excretion was examined in hypotonic saline infused, Inactin anesthetised rats following removal of the adrenals or adrenals and posterior pituitary. Plasma adrenal steroid levels were considerably depressed but still detectable 10-14 days after adrenalectomy. Removal of the posterior pituitary markedly reduced Na+ excretion in adrenalectomized animals implying that Na+ retention following neurohypophysectomy is not dependent on adrenal gland function. In adrenalectomized rats aldosterone administration at 42 pmol/min reduced Na+ excretion and urine flow without significantly changing K+ excretion, though plasma K+ was reduced. In adrenalectomized/neurohypophysectomized rats aldosterone further reduced the already low rate of Na+ excretion and increased K+ excretion, though there was no observable effect on urine flow. The results obtained indicate that the Na(+)-retaining actions of aldosterone are largely independent of posterior pituitary influence. The K(+)-losing action of aldosterone was, however, only observed in animals in which the posterior pituitary was absent. PMID- 2333736 TI - Biosynthetic response of mouse intermediate pituitary gland to induced drinking and dehydration. AB - There are indications that the intermediate lobe peptide alpha-MSH is involved in the regulation of the hydromineral balance in mice and other mammals. The purpose of our studies was to determine whether manipulation of this balance in the mouse could lead to changes in either the rate of POMC biosynthesis in the pars intermedia or to changes in the direction of the processing of the precursor protein to form bioactive peptides. The results show that excess drinking, induced by substitution of drinking water by a 5% glucose solution, causes a rapid increase in POMC synthesis, whereas dehydration has the opposite effect; no evidence could be found that the above treatments have any effect on the processing of POMC, although strain differences were found in level of N-terminal acetylation of newly synthesized melanotropins and endorphins. The changes in various parameters of the hydromineral balance of the animals are consistent with the concept that peptides of the pars intermedia may be involved in regulating plasma aldosterone levels under severe conditions of low plasma sodium concentration. PMID- 2333737 TI - Cold stress during scotophase elicited differential responses in quail pineal, retinal, and serum melatonin levels. AB - Effects of cold stress during scotophase on pineal, retinal and serum melatonin levels were examined in quails. All experimental subjects were housed under a constant room temperature of 23 +/- 2 degrees C and a daily 12 h:12 h light:dark cycle. After 1 week of adaptation, quails were exposed to 4 degrees C in darkness for 60, 120, 180 and 210 min. Immediately following their respective cold treatments, subjects were sacrificed at mid-dark and pineal, retina and serum samples were collected for melatonin radioimmunoassay. Cold stress during scotophase was found to potentiate melatonin levels in the retinas significantly. Conversely, cold exposures in dark significantly decreased melatonin levels in pineal glands and serum. Such diversified responses might be attributed to tissue specific variations in adrenergic and/or dopaminergic receptors responsible for regulating the synthesis and/or secretory mechanisms of melatonin. PMID- 2333738 TI - LH and PRL secretion in ovariectomized spontaneously hypertensive rats. AB - The pulsatile patterns of LH and PRL secretion, and effects of stress on these patterns were examined in ovariectomized normotensive Wistar, spontaneously hypertensive, and genetically matched normotensive Wistar Kyoto rats. Judged by the overall mean of PRL concentrations, PRL levels in spontaneously hypertensive rats were not different from those in Wistar Kyoto rats, but the pulse amplitudes as well as the overall mean concentrations were significantly greater in both Wistar Kyoto and spontaneously hypertensive rats than in Wistar rats. Increases in PRL release during immobilization stress in spontaneously hypertensive rats occurred earlier than in Wistar rats, but the peak levels were not different between the two animal groups, though significantly lower in Wistar Kyoto rats than in Wistar rats. Overall mean of LH concentrations was higher, but pulse amplitude was smaller in spontaneously hypertensive rats than in Wistar Kyoto rats, and in both groups significantly smaller than in Wistar rats. The decrease in LH release owing to stress was similar in all animal groups. A significant association between LH and PRL peaks was evident in all animals, although the rate of association was lowest in Wistar Kyoto rats. In conclusion, the central nervous system mechanisms for both LH and PRL secretion differ markedly in both spontaneously hypertensive and Wistar Kyoto rats from those in Wistar rats, and no specific difference was found in spontaneously hypertensive rats compared with Wistar Kyoto and Wistar rats as controls. PMID- 2333739 TI - Effects of formula protein level and ratio on infant growth, plasma amino acids and serum trace elements. I. Cow's milk formula. AB - The optimum level and ratios of protein to be used in cow's milk formula has recently been under discussion. Healthy term infants were fed from birth exclusively human milk or a formula that varied in protein level or whey: casein ratio: (A) 1.4 g/dl; 55:45, (B) 1.5 g/dl; 55:45, (C) 1.3 g/dl; 55:45, (D) 1.4 g/dl; 60:40, (E) 1.4 g/dl; 20:80. Infants were followed for 12 weeks and blood samples were taken at 2, 4, 8 and 12 weeks. Anthropometric indices did not show any significant differences among groups. Plasma amino acid and BUN levels of the C group were closest to the breast-fed group, while the formula with the highest protein level (B) resulted in high values for some amino acids. When comparing the formulas with 1.4 g protein/dl, the high casein group had the lowest plasma tryptophan levels. Taurine was added to all formulas at a level similar to that of breast milk; plasma taurine levels were similar for all groups. All formulas contained 0.7 mg iron and 0.7 mg zinc/dl; no differences were found among the groups in hematological indices or serum trace elements. These data show that feeding a formula with 1.3 g protein/dl and 55:45 whey: casein ratio from birth will result in growth and metabolic indices similar to those of breast-fed infants, although some plasma amino acid levels are not identical, 1990. PMID- 2333740 TI - Effects of formula protein level and ratio on infant growth, plasma amino acids and serum trace elements. II. Follow-up formula. AB - Infants, that had been formula-fed from birth, were fed follow-up formula with 1.5, 2.2 or 2.9 g protein/dl together with 25 g of cereal/day as supplemental food, or formula only (15 g/dl). Formulas were started at 4 months of age and daily intake, anthropometric measurements and plasma samples taken at 5, 6 and 7 months. Protein intake was 2.0, 3.0 and 3.7 g/kg/d, respectively. Growth data were similar for all groups, as were hemoglobin and serum protein values. BUN values for the group fed only formula with 1.5 g protein/dl were lower than for the group fed the same formula with cereals and the other groups. Plasma amino acids were not affected by the addition of the small amount of cereals to the formula with 1.5 g protein/dl, but significantly higher levels of valine, leucine and histidine were found at 7 months for infants fed the two higher protein levels. The highest protein level also appeared to have a negative effect on plasma zinc levels. These results suggest that a protein level of 1.5 g/dl in follow-up formula (2.0 g/kg/d) is adequate during 4 to 7 months of age and that higher protein levels may be excessive. PMID- 2333741 TI - SCSB method compared to EEG-based polygraphy in sleep state scoring of newborn infants. AB - Knowledge of the sleep state is important in physiological studies since many physiological variables show different properties in different sleep states. The recently developed static charge sensitive bed (SCSB) method allows long-term recordings of body movements, respiration and ballistocardiogram without electrodes attached to the subject. The recordings are easy to carry out and they do not disturb the subject in any way. The recorded variables are basic characteristics of different sleep states. SCSB-recordings and electroencephalography (EEG) based polygraphy as well as blind sleep state scoring were carried out in 8 newborn infants. The positive correlation between SCSB-scoring and EEG-based polygraphy scored by two clinical neurophysiologists was 68.1 and 64.1%. Only in 2% of all epochs was active sleep scored as quiet sleep or vice versa. The results indicate the usefulness of the SCSB method in sleep state scoring of newborn infants. PMID- 2333743 TI - Spontaneous clearance of asymptomatic bacteriuria in infants. AB - In an unselected population of 3,581 infants, 14 girls and 36 boys were found to have bacteriuria verified by suprapubic aspiration. Among the bacteriuric infants, one girl and one boy developed symptoms of pyelonephritis close to the time of detection; the others remained asymptomatic. Eleven girls and 34 boys were left untreated. One of these girls and 7 of the boys became abacteriuric after treatment for respiratory tract infections. Ten girls and 26 boys became spontaneously abacteriuric, with a median persistence of bacteriuria of 2 months in girls and 1.5 months in boys. Recurrences were observed among boys only in those who had been treated with antibiotics. PMID- 2333742 TI - Incidence of Clostridium difficile in hospitalized children. A prospective study. AB - A total of 394 children, aged 0-14 years, referred to a paediatric department were investigated for the occurrence of Clostridium difficile, its cytotoxin in faeces, and its clinical significance in a prospective study over one year. Of the children in the investigation, 337 suffered from gastrointestinal diseases or had been treated with antibiotics prior to the investigation. Twenty-four percent of these children had Cl. difficile in one or more faecal samples and toxin was demonstrated in half of these patients. In 18/148 (12%) of the patients with acute gastroenteritis Cl. difficile was isolated as the only pathogen. In contrast, among 57 control children with no gastrointestinal symptoms and no prior antibiotic treatment significantly fewer harboured Cl. difficile (p less than 0.01). Cl. difficile was isolated with similar frequency in children with or without prior antibiotic treatment. Isolation of Cl. difficile was significantly higher in patients under one year of age (p less than 0.001). In 78% of the patients with Cl. difficile the bacteria were found in faeces during the initial two days of hospitalization indicating that most of the cases were community acquired. The occurrence of Cl. difficile was not influenced by seasonal variation and the distribution between sexes was equal. PMID- 2333744 TI - Comparison of different regimens of prednisone therapy in frequently relapsing nephrotic syndrome. AB - The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was administered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received 19 mg/m2/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75d); however, they were significantly shorter with short-term prednisone therapy (median 33d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment. PMID- 2333745 TI - Renal consequences of immobilisation in children with fractured femurs. AB - Parameters of renal function and calcium homeostasis were studied in 8 children, immobilised for 5-9 weeks with fractured femurs, weekly during immobilisation and fourth weekly following mobilisation until all parameters returned to normal. During immobilisation 1 patient became hypercalcaemic, but all showed an increase in serum calcium and all developed hypercalciuria. During immobilisation all showed diminished urine osomolality after a 12-hour fast (mean 591 +/- 133 mOsm/kg) which improved 4-39 weeks after mobilisation (mean 973 +/- 87 mOsm/kg). Serum creatinine, urinary beta-2-microglobulin and renal ultrasound appearances were all normal. An inverse relationship, R = -0.70, was demonstrated between serum calcium and fasting urine osmolality during immobilisation. Three patients showed diminished urinary concentrating ability beyond 4 weeks after mobilisation. For 1 patient this defect persisted for 8 months and glomerular filtration rate was diminished 9 months after mobilisation, raising the possibility of long term renal damage in immobilised patients. PMID- 2333746 TI - Relation of serum and erythrocyte magnesium levels to blood pressure and a family history of hypertension. A follow-up study in Japanese children, 12-14 years old. AB - Serum and erythrocyte magnesium concentrations (S-Mg, E-Mg) were measured in 122 junior high school students followed up for two years from 12 to 14 years of age, and the relationship to blood pressure and a family history of hypertension were investigated. The subjects who had high S-Mg and E-Mg levels at the first examination two years prior tended to show high levels after this follow-up. There were significant positive correlations between two intraindividual values of S-Mg and E-Mg. A similar tendency was found for blood pressure. Tracking phenomena were observed with these measures. The subjects who had high E-Mg levels at the first examination showed no blood pressure elevation during the two year period. The subjects with a family history of hypertension [FH(+)] showed a higher degree of blood pressure rise during two years than those with no family history [FH(-)], with a significant difference in systolic blood pressure at the age of 14. E-Mg tended to be lower in the FH(+) group than in the FH(-) group with a significant difference in 14-year-old girls. These results suggest that a hereditary predisposition to hypertension is related to magnesium metabolism and that intracellular magnesium deficiency may influence blood pressure elevation in the FH(+) children. PMID- 2333747 TI - Serum haemolytic classical and alternative pathways of complement in infancy: age related changes. AB - The haemolytic activity of complement was evaluated in the serum of healthy children from birth to 2 years of age using the kinetic method for the determination of the time needed to lyse 50% of target red cells (t 1/2). No sex linked differences were observed in any of the age groups studied and the lowest lytic activity levels for both complement pathways were detected in neonates. The two pathways, however, showed different maturation patterns, i.e., lytic activity levels similar to those of adults were reached between the 1st and 3rd month of life (classical pathway) and around the 13th month (alternative pathway). In the age group of 7 to 24 months, the lytic activity of the classical pathway was higher than in adults. The present data permitted us to establish normal ranges of t 1/2 values for the classical and alternative pathways in serum of healthy neonates and children aged 1 to 24 months. PMID- 2333748 TI - Electrolytes, amino acids and proteins in lumbar CSF during the treatment of acute leukemia in childhood. AB - We performed analyses of electrolytes, amino acids, albumin, alpha 2 macroglobulin, gamma-globulin and LDH in the lumbar cerebrospinal fluid of children undergoing treatment for acute lymphoblastic leukemia, non-Hodgkin lymphoma or acute myeloid leukemia. At the time of diagnosis signs of a disturbance of the blood-brain barrier were found in some patients. During induction treatment with L-asparaginase a rise of glutamic acid and a decrease of glutamine occurred. This finding correlated with slowing of the EEG. Treatment with vincristine was associated with a slight drop of sodium and chloride concentration in serum, but not in the cerebrospinal fluid. Central nervous system prophylaxis with cranial irradiation, and to a lesser degree with intravenous medium-dose methotrexate, gave rise to a further deterioration of the blood-brain barrier function as indicated by an increase in albumin, alpha 2 macroglobulin and LDH levels. During radiotherapy the concentration of several amino acids rose, probably due to a disturbance of active carrier mechanisms. Patients with elevated albumin at the end of radiotherapy more often suffered an early leukemia relapse while still on treatment. No other clinical or electroencephalographic correlations of altered barrier function could be found. PMID- 2333749 TI - IgE antibodies to Pityrosporum orbiculare in children with atopic diseases. AB - IgE antibodies to Pityrosporum orbiculare and 16 other species of fungi were measured with the radioallergosorbent test (RAST) in sera of 131 children. The children were 7-18 years old, suffered from atopic diseases and showed a varied allergic profile on a skin prick test (SPT). IgE antibodies to P. orbiculare were found in the sera of 26 of the 131 children. A higher proportion of the P. orbiculare RAST positive children than of the negative ones had current eczema (p less than 0.0001). In a stepwise logistic regression analysis of SPT and RAST data, the occurrence of serum IgE antibodies to P. orbiculare had the highest explanatory value for current eczema. Ten of 15 children with current atopic eczema and total serum IgE of greater than 500 kU/l had serum IgE antibodies to P. orbiculare. Twenty-four of the 26 P. orbiculare RAST positive children harboured serum IgE antibodies to other fungi. The strong relationship between atopic eczema and the occurrence of IgE antibodies to P. orbiculare indicates that these antibodies may be pathogenetically important in at least some patients with atopic eczema and this gives another dimension to this common skin disease. PMID- 2333750 TI - Scaly lesions on the feet in children--tinea or eczema? AB - Fungal cultures were negative in 20 children aged 1 to 14 years with a clinical picture consistent with juvenile plantar dermatosis. During the same period (April 1987 to August 1988) 4 cases of tinea pedis were seen in the same age group. The important difference between juvenile plantar dermatosis (with or without associated atopic disease) and the clinical picture seen in dermatophytic infection is described. PMID- 2333751 TI - Learning disabilities in children: significance of low-level lead-exposure and confounding factors. AB - The hypothesis that low-level lead absorption is a risk factor for learning disabilities in school children was examined in the municipality of Aarhus, Denmark. During 1982-1983, a total of 1,302 children in the first grade (54% of the eligible population) delivered shed deciduous teeth. The lead concentration in the circumpulpal dentin was used as an indicator of the cumulated lead absorption, and 200 cases (high-lead) and controls (low-lead) were selected, and matched for socioeconomic group and gender. The parents were interviewed regarding the child's development and past medical history. Possible confounders were identified and controlled for in a logistic multivariate model. The influence of lead absorption became statistically significant only after exclusion of the children with proven medical risk factors, thereby the adjusted odds ratio in the weighted analysis was changed from 2.2 to 4.3. Thus, in a Scandinavian low-level lead-polluted area, lead absorption appears to be a risk factor for learning disabilities. PMID- 2333752 TI - Bone mineral analysis in obese children. PMID- 2333753 TI - Intestinal absorption of D(+) xylose in newborns of different gestational ages and sizes. PMID- 2333754 TI - Phototherapy failure in jaundiced newborns with hereditary spherocytosis. PMID- 2333755 TI - Glomerular filtration rate increases with body mass in children with reduced nephronic population. PMID- 2333756 TI - Saethre-Chotzen syndrome associated with defective neutrophil chemotaxis. AB - An 11-month-old male infant with Saethre-Chotzen syndrome and recurrent respiratory infections is described. Persistent extremely high leukocytosis warranted evaluation of neutrophil functions. It was found that the opsonophagocytic activity was normal, but neutrophil chemotaxis was markedly decreased. Further studies pointed to an intracellular neutrophil defect causing this motility dysfunction. PMID- 2333757 TI - Occipital osteodiastasis. A rare complication in cephalic delivery. AB - A case of occipital bone osteodiastasis in an infant born by cephalic vaginal delivery is presented. Cerebral echography and CT scan did not show posterior fossa haemorrhage. Neurological assessment at three years of age was completely normal. PMID- 2333758 TI - Adverse drug reactions causing hospital admission in an elderly population: experience with a decision algorithm. AB - An adverse drug reaction (ADR) decision algorithm was used in the review of 100 consecutive hospital admissions of elderly patients cared for by family physicians. The algorithm is a valid methodologic alternative to using pharmacological experts for verification of an ADR. In this study, the algorithm was easily applied by family physicians, and the results were similar to those reported by expert clinical pharmacologists. Nine percent of our elderly patients' hospital admissions were caused by ADRs that were due to usual doses of medications commonly prescribed for elderly patients. Average age of patients and number of medications were similar for persons with and without ADRs. The algorithm can be useful to physicians investigating ADRs for clinical research, physician education, quality assurance, and improved patient care. PMID- 2333759 TI - Varicella during pregnancy: the timing of effective treatment. AB - Maternal varicella infections during pregnancy can be either benign or disastrous for the infant according to the timing of infection during gestation. We report a case of varicella occurring at term that was managed successfully. Appropriate management includes tocolysis, unless contraindicated, and varicella-zoster immune globulin (VZIG) administered to the mother within 72 hours of delivery, or to the neonate when the mother's rash appears within 48 hours after delivery. Treatment can markedly decrease the risk of mortality and severe morbidity in the relatively immunocompromised infant. PMID- 2333760 TI - Accidental exposure to HIV infection by health care workers. AB - The health care worker's exposure to HIV presents a cascade of real and potential problems. Medical, psychological, employment, and legal problems present ongoing challenges, often in uncharted territory. The references listed below provide additional information to help in both individual cases and in prospectively setting up programs and action plans for hospitals and offices. PMID- 2333761 TI - More on testing for HIV. PMID- 2333762 TI - Dosage of zidovudine for treatment of AIDS. PMID- 2333763 TI - Expanding the family practice model. PMID- 2333764 TI - Writing about writing, Part III: Twenty common word usage errors. PMID- 2333765 TI - American Board of Family Practice statistics. PMID- 2333766 TI - Breast screening. PMID- 2333767 TI - NSAIDs. PMID- 2333768 TI - Improving mammography recommendation: a nurse-initiated intervention. AB - We attempted to improve our compliance with recommendations for screening mammography, according to the American Cancer Society (ACS) guidelines, for eligible women patients seen by family practice residents by using a multipart intervention designed to eliminate identified barriers of knowledge and behavior on the part of the residents. Copies of the ACS cancer screening guidelines were posted in all examination and conference rooms and were provided to all residents. The intervention addressing the behavioral barriers had three components: (1) identification by the nursing staff of eligible women who were overdue for a mammogram as they presented for care, (2) completion of a checklist by residents indicating whether a mammogram was or was not recommended and why, and (3) a nurse-initiated backup reminder system for patients who escaped the primary checklist system. An audit of 200 preintervention and 270 postintervention charts showed statistically and clinically significant increases in mammograms recommended or done. Similar statistically significant increases were found in a cohort of 111 charts of patients in both the pre- and the postintervention audits. Results indicate that an intervention designed to eliminate identified resident-dependent barriers to compliance with screening mammography guidelines can be effective in increasing recommended mammography rates. PMID- 2333769 TI - Vaginal diaphragm rings in the treatment of stress urinary incontinence. AB - To assess the effectiveness of wearing vaginal diaphragm rings in the treatment of stress urinary incontinence, 10 women with genuine stress incontinence were studied. Patients underwent urodynamic evaluation and perineal pad testing before and after fitted diaphragm rings were in place. Patients kept symptom diaries for 1 week without the ring and then for 1 week with the ring. They also gave an overall subjective evaluation of their experience. Urodynamic findings were essentially unchanged by wearing diaphragm rings. Trends toward improvement were observed in the results of pad tests and symptom diaries. Four of the 10 women experienced clinically significant improvement in amount of urine lost during pad tests, number of leaks per week, and overall assessment of response. Vaginal diaphragm rings may be an effective treatment for some women with stress urinary incontinence. PMID- 2333770 TI - [Reform of medical education]. PMID- 2333771 TI - [Body height of Portuguese school children. Evolution in the last half century]. AB - The height values of 122 boys and 124 girls, 7 to 11 years old, from 19 primary schools of the central area of Portugal were evaluated in 1988. The values from boys of all ages and girls younger than 9 years were normally spread, according to american (NCHS-USA 1976) standards. Girls older than 9 years were relatively shorter which could be related to the late puberty of these country girls. These figures are about 4 cm higher than those collected from portuguese school children born in 1964. PMID- 2333772 TI - [Silent myocardial ischemia: 3 years' experience with Holter]. AB - The authors describe their experience concerning silent myocardial ischemia diagnosed by Holter monitoring technique, and present an update review about this issue. The new concepts of stunned and hibernated myocardium are analyzed, as well as the concepts of ischemic cascade, total ischemic burden and variable residual coronary reserve. Diagnostic methods and therapeutic decisions are also reviewed. PMID- 2333773 TI - [Structuring a clinical information system for hospital services: BASELINE]. AB - Clinical database systems have been in use since 1972, but they still fail to meet most of the requirements they were aimed at. This includes not only the management of administrative tasks, but particularly the support of medical activities. Our study presents an experimental model of a clinical database system for general hospitals, mainly dedicated to the support of some basic, fundamental clinical activities, namely the management of baseline patient data. This model is based on a modular concept, and its core is represented by a Minimal Data Base Set designed to meet the specific requirements of each Department and of each distinct area within a Department. The system does not interfere with routine clinical work and tries to offer a high level of services to users. A number of utilitary programs simplify user interaction with the system, such as a menu-driven data-entry program, a semi-automatic codification program that follows the OMS/ICD-9-CM coding system, and a menu-driven program for data retrieval. Basically, this system can be helpful for the automatic edition of clinical reports and the retrieval of patient records meeting conditions specified by the clinician. PMID- 2333774 TI - [Hereditary protein C deficiency and portal vein thrombosis]. AB - Inherited defects of the natural coagulation inhibitors predispose patients to thrombosis. These disorders have similar clinical presentations with a strong family of thrombosis, episodes of recurrent venous thromboembolism, beginning in early adulthood. We report a case of upper gastrointestinal bleeding in a patient with portal hypertension due to portal-vein thrombosis secondary to hereditary protein C deficiency, an association that has seldom been reported. We conclude that protein C deficiency should be investigated in thrombotic states, namely after more frequent causes have been excluded. PMID- 2333775 TI - [Phlebectasis of the external jugular vein]. AB - Phlebactasia of the external jugular vein is a rare nosological entity. Few reports appeared in the world literature. Clinically it presents as a cervical mass enlarging with a Valsalva maneuver. The Authors present one clinical case, emphasizing the possibilities of Computed Tomography (CT) in a precise diagnosis, etiological and topographical, without using other invasive modalities. PMID- 2333776 TI - [Immunosuppression therapy in peripartum myocardiopathy]. AB - The dramatic clinical recuperation of a thirty years old, Caucasian female, with peripartum cardiomyopathy, treated with azathioprine and prednisolone, is described. The maintenance of the same degree of ventricular dilatation and fractional shortening (14%) on serial echocardiograms inspite of complete regression of cardiac congestion was the most intriguing feature of this clinical case. PMID- 2333777 TI - [The relation of basic sciences and medicine: institutional, professional and pedagogic implications]. AB - The author analyses the problems involved in the transfer of concepts and techniques from the basic sciences to the medical practice. The number of skills to be acquired in the course of medical training restricts the inclusion of the teaching in depth of basic sciences in the Curricula of medical schools. Post graduate teaching cannot be used for that purpose unless it is geared to MD's fully dedicated to research. New discoveries in the basic sciences which may be relevant to medicine can only be made available to doctors through the development of basic research in medical institutions, playing the role of centers of excellence. Since basic research in the medical field is, by its nature, interdisciplinary, such policy entails the recruitment of scientists with non-medical background to whom career opportunities comparable to those of the doctors should be made available. In countries with small scientific communities the most important step in the stimulation of basic research is the identification of young talents and the support of existing productive groups. In the mid term, molecular biology, neurobiology and signal processing (specially image processing) seem to be promising areas from a medical point of view. Science should be considered a very important component of the cultural activity of a country. PMID- 2333778 TI - [Oncologic pathology at an internal medicine service]. AB - A retrospective survey of the patients with oncological disease admitted to our Department of Internal Medicine in 1987 was conducted to determine its prevalence and to draw a descriptive profile of these patients' admissions. The results show that oncological diseases were the second cause of hospital admissions that year (12%) only exceeded by cardiovascular diseases. About 60% of the patients had neoplasms already diagnosed elsewhere and were admitted for complications or with therapeutic purposes; in 40% of cases the disease was diagnosed in our Department. A wide variety of hematological and non-hematological tumors was found. There were some difficulties in interdisciplinary coordination in the diagnostic and therapeutic approach. More than 50% of the patients had advanced disease, limiting medical intervention to supportive measures. In about 60% of them were oriented to primary care physicians after physicians after discharged from Hospital. These results suggest the dispersion of the available resources for the diagnosis, treatment and follow-up of oncological diseases in our population. A better cancer patients' assistance in Portugal will depend on the promotion of national cancer registers as well as the improvement of cancer prevention and early detection programs, according to the directives of EEC and WHO. We also emphasize the need of investment on undergraduate and postgraduate education programs, specially for primary care physicians. PMID- 2333779 TI - What do physicians in practice do to prevent osteoporosis? AB - Osteoporosis-associated fractures are a major public health problem in the United States. Although clinicians and policy groups have advocated estrogen replacement therapy and other clinical measures to prevent osteoporosis, few studies have assessed whether these measures are being adopted by physicians in practice. The purpose of this study is to evaluate physicians' use of osteoporosis prevention measures and to assess the impact of physician specialty and practice setting on osteoporosis prevention performance. A survey of nearly 300 physicians was carried out in a large metropolitan area. Gynecologists, general internists, and cardiopulmonary specialists were included from one of three practice settings: fee-for-service private practice, full-time academic medicine, or a large health maintenance organization. Most physicians, regardless of clinical specialty or practice setting, report that they advocate exercise and calcium supplementation. Few physicians prescribe estrogen replacement therapy (ERT) for the majority of their postmenopausal patients. Although there are minimal differences among the three types of practice settings examined, ERT varies markedly by clinical specialty. Of the gynecologists surveyed, 37% report prescribing ERT for the majority of their postmenopausal patients to prevent osteoporosis compared to only 7 and 5% of general internists and cardiopulmonary specialists, respectively (chi 2 = 45.3, p less than 0.0001). Although the efficacy of exercise and calcium supplementation to prevent osteoporotic fractures has not been well established, these measures are commonly advocated by both generalists and subspecialists. Although gynecologists are significantly more likely to prescribe ERT to prevent osteoporosis than the other clinical specialists, in general very few physicians prescribe ERT for most postmenopausal patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333780 TI - Response to retreatment of malignant hypercalcemia with the bisphosphonate AHPrBP (APD): respective role of kidney and bone. AB - Malignant hypercalcemia is caused by both increased bone resorption and enhanced tubular reabsorption of calcium. First, the response to an infusion of APD was compared in two groups of patients: 23 with breast cancer versus 20 with squamous cell cancer. The decrease in plasma calcium was smaller in the latter group (p less than 0.05 at day 14), due to increased tubular reabsorption of calcium (TmCa/GFR 2.20 +/- 0.05 versus 2.58 +/- 0.06 mmol/liter; p less than 0.001), whereas the degree of bone resorption reflected by urinary hydroxyproline was identical. Therefore, at a given initial plasma calcium level, the type of tumor (on which TmCA/GFR depends) seems to be a determinant for the effectiveness of the treatment. Second, the response to the initial treatment was compared with that to a second treatment with the same dose in 12 patients whose malignant hypercalcemia relapsed. Within 9 days, plasma calcium decreased from 3.46 +/- 0.10 to 2.50 +/- 0.10 mmol/liter after the first course, but only from 3.37 +/- 0.08 to 2.79 +/- 0.09 mmol/liter after the second course (p less than 0.01). TmCa/GFR was similar before the first and the second treatment and did not vary during the days following the infusion of APD. Initial urinary hydroxyproline was slightly but not significantly higher before the second treatment. It dropped following both APD courses, but to a lesser extent after the second treatment, reflecting higher bone resorption or possible resistance to bisphosphonate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333781 TI - A new method for automatic recognition of the radiographic trabecular pattern. AB - This study reports a method to describe and analyze the structure of the trabecular pattern seen on radiographs of the distal radius. The structure is measured and related to the bone mineral density (BMD) of the lumbar spine measured by dual-photon absorptiometry. Radiographs of hand and wrist combined with additional information of the bone mineral density of the vertebrae serve as testing material. With a computer-aided imaging system, a part of the depicted radius is scanned. The image is filtered and segmented into a bilevel picture consisting of a light network with dark meshes. Seven features of the bilevel picture are measured and analyzed. It is shown that six features correlate significantly with the bone mineral density measured at the lumbar spine, although the correlations between the trabecular pattern and the BMD are too weak to allow precise predictions of BMD values for individuals. Nevertheless, the correlations confirm the existence of a relationship between the radiographic trabecular pattern and the bone mineral density of the lumbar spine. The method is worth being further developed for use on individual patients. It provides a noninvasive tool to make an objective and quantitative assessment of the trabecular pattern. PMID- 2333782 TI - An automatic method for bone histomorphometry: assessment with reference to usual static and dynamic parameters. AB - To perform a fast and reproducible analysis in bone histomorphometry, we developed an automatic method for calculating static and dynamic parameters. A color automatic image analyzer (SAMBA 200) was used to obtain the usual parameters of bone histomorphometry: bone volume (Cn-BV%TV), osteoid volume (Cn OV%BV), and osteoid surface (Cn-OS%BS). A specialized algorithm was designed for calculation of the mineral apposition rate (MAR). Eroded surface (Cn-ES%BS) was read in a semiautomatic mode using a cursor. To validate this program, we input 30 samples from patients with bone disease (20 osteoporosis, 6 renal osteodystrophy, 2 osteomalacia, and 2 hyperparathyroidism) using manual and automatic modes. The results obtained showed a highly significant correlation with the usual manual method for all parameters: OS/BS, r = 0.93; OV/BV, r = 0.98; MAR, r = 0.90. With the automatic method, larger values were found for osteoid parameters and MAR and lower values for BV/TV. There were no statistical differences for OV/BV and MAR when compared to the reference manual method. This study establishes that automatic measurements of osteoid parameters and MAR can be performed by a fast analyzer with as good reproducibility and accuracy as the manual method. PMID- 2333783 TI - Exercise patterns and trabecular bone density in college women. AB - To assess the effects of physical activity patterns on trabecular bone density in college women, we studied three groups of nonsmoking eumenorrheic women with different (but chronic) exercise regimens. There were nine sedentary (SED) women exercising less than 1 h/week, nine women who performed aerobic (AER) exercise greater than 2.5 h/week, and nine women who supplemented aerobics with muscle building activities (MB) for more than 1 h/week. Resting energy expenditure, calorie, protein, and calcium intake, total body weight, and body mass index were not statistically different among the three groups. AER and SED women had similar lumbar bone mineral density (BMD). MB women had significantly greater spinal bone density (p less than 0.007 versus SED, AER). IGF-1 (insulin-like growth factor) concentrations were greatest in MB (p less than 0.01), and hours muscle building per week correlated with IGF-1 (r = 0.86, p less than 0.03). For all 27 women (mean age 24.5 years), body mass index was the single best predictor of lumbar BMD (r = 0.42, p less than 0.03); hours in muscle-building exercise per week conferred an additive effect on lumbar BMD. This cross-sectional study of young women suggests chronic muscle-building exercises may augment lumbar bone mass. The additive effect of anaerobic exercise on bone density may be mediated by both local weight-bearing changes and possible systemic factors. PMID- 2333784 TI - Zinc excretion in osteoporotic women. AB - The relation of zinc to the aging skeleton was investigated in 140 women aged 36 85 years, mostly postmenopausal, who attended the Jerusalem Osteoporosis Center. Osteoporosis was determined by lumbar spine radiograms (Smith index). Bone density (BD) of the distal radius was assessed by Compton spectroscopy and bone mineral content (BMC) at the same site by single-photon absorptiometry. Urine samples (24 h) were analyzed for zinc (UZn), hydroxyproline (UHP), calcium (UCa), magnesium (UMg), and phosphorus (UP) and expressed per gram creatinine. Patients with definite osteoporosis (n = 94) compared to subjects with borderline or no osteoporosis (n = 34) had a significantly higher mean age (67.4 versus 58.6 years), postmenopausal age (PMA, 19.9 versus 11.0), UZn (811 versus 581), UHP (23.5 versus 18.2), and UMg (90.4 versus 74.3). Urinary calcium UCa and phosphorus UP were similar in both groups. The bone mass measurements BD, BMC, and CI were lower in the osteoporotic group. Hyperzincuria (UZn above 800 micrograms/g creatinine) was found in 41 osteoporotic patients (45%) compared to 6 subjects in the control group (17%). In view of the positive correlation between UZn and age (r = 0.35, p = 0.001) and to eliminate the effect of age, a separate analysis was performed for 66 subjects under the age of 65 in whom the mean age was similar for the osteoporosis patients (n = 38) and control group (n = 28). Nevertheless, the osteoporosis patients still had a significantly higher mean UZn and UHP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2333785 TI - Serum osteocalcin (BGP) levels in normal men: a longitudinal evaluation reveals an age-associated increase. AB - Serum levels of bone gla protein (BGP) have been reported to increase with aging and hence to reflect an age-related increase in bone remodeling activity. To evaluate the relationship between aging and serum BGP levels in a study of longitudinal design, we measured BGP concentrations in 77 normal men at 6 month intervals over a 3 year period. Mean BGP levels at the onset (4.95 +/- 1.5 ng/ml) increased significantly during the study (p = 0.004), and the mean of individual BGP slopes was positive (0.38 +/- 0.6 ng/ml per year, p = 0.0001). The rate of change in BGP was not related to serum creatinine levels or dietary calcium intake. PMID- 2333786 TI - Bone changes occurring early after cessation of ovarian function in beagle dogs: a histomorphometric study employing sequential biopsies. AB - The beagle dog model has been established by our laboratory as a useful animal model to study bone loss after cessation of ovarian function. Previously we demonstrated bone loss associated with an osteoblastic insufficiency at 4 months after ovariohysterectomy (OHX). This study was designed to evaluate by four sequential monthly bone biopsies the development and course of the histologic bone abnormalities after OHX. We found cancellous bone volume, trabecular density, and wall thickness to be decreased (p less than 0.05) and trabecular separation increased (p less than 0.05) as early as 1 month after OHX. After 2 months, there was a decrease in mineralizing surface and mineral apposition rate (p less than 0.05). Volume and surface of osteoid were increased after 3 months (p less than 0.05), and there was an increase in the number of osteoblasts (p less than 0.01). No histologic signs of increased resorption were observed during the experiment. However, the findings of low bone volume with decreased trabecular density and increased separation without a change in trabecular plate thickness 4 weeks after OHX suggest that a dramatic increase in resorption must have taken place soon after OHX. These results point to an early phase of initiation of bone loss related to hyperresorption followed by a maintenance phase of low bone mass ascriblastic insufficiency. The events that stimulate the early initiating phase after cessation of ovarian function, the factors contributing to it, and the direct demonstration of hyperresorption await further studies. PMID- 2333787 TI - Aminohydroxybutane bisphosphonate inhibits bone loss due to immobilization in rats. AB - The purpose of this study was to document the effects of aminobutane bisphosphonate (AHBuP) on bone remodeling during immobilization in rats. Male Sprague-Dawley rats underwent unilateral sciatic neurectomy after receiving two daily subcutaneous injections of 0, 0.01, 0.10, or 1.0 mg P per kg AHBuP. Rats were sacrificed at 24 h or 10 or 20 days postimmobilization. Femora were ashed and tibiae were prepared for histomorphometric analysis. AHBuP was effective in inhibiting bone loss due to immobilization in a dose-dependent manner. The percentage loss of femoral ash weight due to immobilization decreased in a dose dependent manner. In vehicle-treated rats, there was a significant decrease in trabecular bone volume (TBV) in the immobilized tibiae compared to the normal tibiae; in AHBuP-treated rats there was a dose-dependent increase in TBV both in the immobilized and control tibiae. The osteoid surface extent was decreased in AHBuP-treated rats in a dose-dependent manner. The mineral apposition rate was altered only in the intact leg of rats treated with 0.1 and 1.0 mg P AHBuP per kg compared to vehicle treated. Osteoclast number per mm was reduced by AHBuP treatment. In conclusion, aminohydroxybutane bisphosphonate effectively prevented the bone loss due to immobilization in this system. PMID- 2333788 TI - Location of osteoclast precursors in fetal rat calvaria cultured on collagen gels. AB - Although osteoclasts are derived from hematopoietic cells, the exact identity of their precursors and the mechanism for their recruitment onto bone surfaces remain unclear. We wished to study their differentiation in the fetal rat calvaria and to locate its source of osteoclast precursor cells. Osteoclasts were detected by neutral red staining or cytochemical reaction for acid phosphatase of intact bone (cell number and area measured by computerized image analysis) or in cryostat sections of bone (enzyme activity measured by quantitative cytochemistry). Histology of semithin sections of fixed bones was also examined. The 19 day calvariae contained few mature osteoclasts. After 48 h culture on gels of type 1 collagen (1.5 mg/ml) supplemented with 5 mM calcium beta glycerophosphate, 10 mM proline, and 2 micrograms/ml ascorbic acid, numerous large osteoclasts were seen on their endocranial surfaces. In contrast, cell morphology and enzyme activity deteriorated in bones cultured in liquid medium. The cells that formed in vitro rapidly responded to calcitonin by contraction. Stripping of endocranial membranes from the calvariae prevented osteoclast formation in culture, but these cells were seen when "stripped" bones had been cocultured with their membranes for 48 h or with intact 16 day calvariae (well before the onset of osteogenesis). Few osteoclasts were found when an 0.22 micron filter was inserted between the stripped calvaria and the endocranial membranes. We conclude that the endocranial membranes, which contain the meningeal blood vessels, are a major source of osteoclast precursors and that these cells are present in calvarial tissue even before the onset of osteogenesis. PMID- 2333789 TI - Age-related bone loss in women. PMID- 2333790 TI - Dysfunction in the single-parent and only-child family. AB - As the average size of the family decreases, controversy over the child at risk in relation to family structure has intensified. There is a great deal of literature on single-parent families, but little delineation of specific subgroups. In this pilot study, twelve adolescent inpatients who were an "only child" in single-parent families were compared to a control group of adolescent patients matched for sex, family income, and diagnosis. In some "minimal families" (single parent/only child), the interpersonal transactions were examined as the crucial parameter in formation of dysfunction. Statistical analysis of the data supported the hypothesis that in this clinical sample, the single-parent/only-child families and their adolescents would display a greater degree of disturbance than the control group. Some theoretical and clinical issues related to this group are discussed. PMID- 2333791 TI - Self-concept as a factor in the quality of diets of adolescent girls. AB - The effect of self-concept on the quality of diets of adolescent girls was investigated. Scores for self-concept as measured by the Tennessee Self Concept Scale (TSCS) and fat area values were obtained from 160 15-year-old girls. Twenty four-hour dietary recall interviews were conducted with a random subsample of 40 girls. Mean dietary adequacy ratios (MARs) were calculated to assess dietary quality. Girls in this study had larger arm fat areas than did their national counterparts. Mean intakes of energy and nine nutrients met or exceeded their respective RDAs except for vitamin A, calcium, and iron. MAR values were correlated positively with Self-Satisfaction scores and negatively with carbonated beverages, candy, and baked desserts. Fat area values were correlated negatively with Physical Self scores. Significant predictors of MAR values below 80% were Total Conflict, Moral-Ethical Self, Family Self, Identity, and Physical Self scores. PMID- 2333792 TI - Effects of rational emotive education on the rationality, neuroticism and defense mechanisms of adolescents. AB - The purpose of this study was to assess the efficacy of rational emotive education (REE) as a mental health prevention program for adolescents. The subjects included 109 eleventh- and twelfth-grade students enrolled in four introductory psychology courses, and who were divided into experimental and control classes. Experimental subjects received 12 biweekly sessions of REE. Subjects were pre- and posttested on three measures of psychosocial adaptation: the Rational Behavior Inventory (RBI), the Defense Mechanism Inventory (DMI), and the Eysenck Personality Inventory (EPI). The effects of REE upon behavior were also examined by comparing academic effort grades, number of detentions, and grade point averages. Overall results showed significant positive changes in use of more adaptive defense mechanisms and in academic effort grades in the predicted direction. No significant changes occurred on the other measures. However, as a distinctive group, 17-year-olds demonstrated a significant reduction in neuroticism scores and a significant increase in academic effort grades. PMID- 2333793 TI - Sexual decision making in young black adolescent females. AB - Participant observation and a questionnaire guide were used to conduct in-depth interviews with five 14-year-old, black, pregnant or recently delivered girls to obtain a broad and detailed view of perceptions and interpretations of the factors that led to the initiation of sexual activity and the decision to maintain the pregnancy that resulted. Four key and several supporting factors that influenced the girls' sexual decisions emerged from the data. The key factors centered around the girls' attempt to establish a relationship based on trust, a belief in their lack of vulnerability to become pregnant, family structure, and their beliefs about the alternatives available once a pregnancy was confirmed. Some of the findings were consistent with those reported in the literature, while others were not. Further research is needed on the father of the infant as well as the mother of the adolescent girl to assess their perceptions of the factors they believe influence teenagers' sexual decisions. PMID- 2333794 TI - Adolescent health status, behaviors and cardiovascular disease. AB - This study tracked levels of risk indicators over a four-year period in 356 matched high school students in central Illinois. Selected clinical measures of health status (height, weight, triceps skinfold thickness, body mass index, blood pressure and pulse) and self-reported behavior were assessed. From these measures, subjects were identified as potentially at risk if their scores equaled or exceeded the 75th percentile for their age, sex, and race. Results indicated that 54% of this at-risk group also had negative health behaviors (smoking, physical inactivity, high salt, red meat and fat consumption, and alcohol intake). Some of these behaviors demonstrated strong, positive correlations with health status as shown by chi-square, t test, analysis of covariance, and Pearson product-moment correlation statistics. Thus, those students warranting preventive intervention and referral follow-up programs before adulthood were identified. PMID- 2333795 TI - The relationship of alcohol, tobacco, marijuana, and other illegal drug use to delinquency among Mexican-American, black, and white adolescent males. AB - This study examined the relationship between drug use and delinquent behavior among 348 high school males (154 whites, 172 Mexican-Americans, and 22 blacks) and 89 adjudicated delinquent males confined to a maximum-security facility for violent and repeat offenders (37 whites, 25 Mexican-Americans, and 27 blacks). Data were collected in the spring of 1986 using self-administered questionnaires. Analyses were performed separately for each racial subgroup. Simple correlations revealed that self-reported alcohol, tobacco, marijuana, and other illegal drug use were all significantly related to both minor and violent delinquency for all three racial groups. Multiple regression analysis revealed that the use of these substances accounted for 40% to 47% of the variance in minor delinquency and for 59% of the variance in violent delinquency among blacks, 53% of the variance in violent delinquency among Mexican-Americans, and 34% of the variance in violent delinquency among whites. The best predictors of violent delinquency were the frequent use of illegal drugs other than marijuana and use of tobacco, in that order, among Mexican-Americans; the frequent use of other illegal drugs, marijuana, and tobacco, in that order, for whites; and the frequent use of illegal drugs, followed by marijuana, for blacks. PMID- 2333796 TI - Comparisons of female and male early adolescent sex role attitude and behavior development. AB - This study contrasted female and male early adolescent sex role attitude and behavior development in an ecological context as defined by Bronfenbrenner. Data were the results of a state-wide survey of early adolescents and their parents. Hierarchical multiple regression was used to test both sex role attitude development and behavior development models. Only the models for attitude development were significant. The level of traditionalism of female sex role attitude development was significantly influenced by maternal employment, the level of traditionalism of the father's sex role attitudes in interaction with the amount of time he spent with his daughter, and chronological age. In contrast, the level of traditionalism of male sex role attitude development was significantly influenced by the level of traditionalism of the mother's sex role attitudes in interaction with the level of closeness to the mother that was reported by the son, and both mother's and father's perception of pubertal age. The implications of the findings for human development theory, early adolescence as a stage of development, and sex role theory and research are discussed. PMID- 2333797 TI - Alcohol use as a situational influence on young women's pregnancy risk-taking behaviors. AB - Recent studies have found that many young women just beginning their sexual lives use alcohol prior to intercourse. A large number appear to drink heavily enough prior to sex to compromise their ability to use contraceptives. The question emerges whether there is a relationship between drinking before intercourse, the nonuse of birth control methods, and unplanned pregnancies. The present research describes 43 instances of intercourse which resulted in unplanned pregnancies in 14- to 21-year-olds. Variables examined included alcohol use prior to sex, amount of alcohol consumed, the use of other drugs, the planning of intercourse, respondents' stated reasons for nonuse of contraceptives, and other general demographic data. PMID- 2333799 TI - Coming-of-age among contemporary American Indians as portrayed in adolescent fiction. AB - This paper examines the dominant themes evident in contemporary novels involving American Indian adolescents. Nine novels written between 1971 and 1986 are reviewed. In contrast to earlier novels, those reviewed here reflect greater realism toward and less stereotyping of American Indians. Several themes in the novels are reflective of problems and issues confronting adolescents from a variety of backgrounds. The more salient themes, however, are specific to American Indian culture, including the prejudice and discrimination experienced by American Indians, the hopelessness and helplessness of an American minority group, racially mixed marriages of parents, alienation from non-Indian peers, Indian and Anglo friendships, the search for a sense of self, recapturing Indian traditions, and Indian spirituality. PMID- 2333798 TI - Suicidal tendencies and ego identity in adolescence. AB - Studies distinguishing between adolescent suicide attempters and others usually deal with demographic, physiological, or familial contributing factors. The objective of this study was to investigate the relationship between ego identity development and suicidal inclinations at adolescence. The main hypothesis was that ego identity formation at adolescence may serve as a "buffering" force by providing stability, continuity, meaningfulness, social recognition, commitment, and inner strength against suicidal attempts. Two groups of adolescents, a suicidal group (n = 10) recruited from mental health clinics and a normative group (n = 30), were matched for intelligence, demographic variables, and socioeconomic status. The Adolescent Ego Identity Scale (AEIS; Tzuriel, 1984) and the Israeli Index of Potential Suicide (IIPS) based on Zung's (1974) scale were administered to both groups. The results indicated that the normative group scored significantly higher than did the suicidal group on all but one of the AEIS factors and lower on the IIPS. A MANOVA carried out on ego identity factors revealed a significant overall difference between the two groups. Univariate analyses indicated that most of the ego identity factors differentiated between the two groups. Negative correlations between AEIS and IIPS were found in both groups, especially between total AEIS score and IIPS in the normative group (r = .89, p less than .001). The findings in general confirm the "buffering" force hypothesis. These preliminary results are discussed in regard to theoretical and preventive aspects. PMID- 2333800 TI - Causal attributions for losing as perceived by adolescents. AB - To assess the causal attributions for losing perceived by both early and late adolescents, a sample of 150 high school students responded to a questionnaire comprising three categories of activities (sport, academic, and social) in which they had not won or achieved a desired outcome. The obtained attributions for not winning were categorized into four areas: task difficulty, luck, effort, or ability. Adolescent girls indicated significantly more internal attributions and boys more external attributions. Seventh graders' attributions were external and twelfth graders' were internal. No differences emerged as a function of high and low self-esteem. Implications for the structure of achievement tasks are discussed. PMID- 2333801 TI - AIDS: late adolescents' knowledge and its influence on sexual behavior. AB - Approximately 300 late adolescents were surveyed to assess their knowledge of AIDS, and to determine if and how their sexual behavior had changed as a result. Findings suggested that late adolescents were quite knowledgeable regarding AIDS and its transmission; however, only about one-third had altered their sexual behavior as a result of fear of the disease. Findings are discussed in terms of the need for AIDS education, and recommendations are presented. PMID- 2333802 TI - The effect of social support on adolescent mothers' styles of parent-child interaction as measured on three separate occasions. AB - The purpose of this study was to determine the effect of social support on parent child interaction in a group of 19 adolescent mothers. The subjects participated in a 20-week model demonstration program in which they worked in a preschool classroom with skilled caregivers who modeled facilitative styles of interacting with young children. Each subject was videotaped while interacting with a 1- to 2 year-old child upon entering the program, midway through the program, and at the end. Results showed that girls who were 16 years or older significantly increased their frequency of using responsive, engaging, and elaborative styles of behavior. Those under age 16 did not show significant changes in these three behaviors. Overall, subjects significantly increased the duration of time they spent observing the child's play behavior. PMID- 2333803 TI - A cognitive/affective empathy training program as a function of ego development in aggressive adolescent females. AB - This study investigated the effects of an affective/cognitive empathy training program on level of empathy in 24 aggressive adolescent females in a residential treatment center. In addition, the relationship between empathy and level of ego development was explored. Empathy was defined as a psychological construct regulated by both cognitive and affective components, interacting in a systemic manner to produce emotional understanding. Subjects were pretested on measures of affective empathy, cognitive empathy, and Loevinger's scale of ego development. High and low scores on the measures of ego development were defined by a median split. Following random assignment to groups, experimental subjects were exposed to four 1.5-hour training sessions directed at increasing levels of affective and cognitive empathy. Posttests revealed significant positive relationships between ego development and both measures of empathy. Training significantly increased levels of affective empathy, while increases in cognitive empathy were unremarkable. There was no difference between high and low ego development scorers in their ability to profit from training. The hypothesized systemic relationship between affective and cognitive empathy was also supported by the findings. PMID- 2333804 TI - Clothing interests, body satisfaction, and eating behavior of adolescent females: related or independent dimensions? AB - Adolescents' clothing interests, body satisfaction, and eating behaviors were examined for conceptual dimensions and possible interrelationships. Generation of hypotheses was the goal of this exploratory research. Instruments measuring adolescents' dress concerns, body satisfaction, and eating behaviors were administered to 751 females. Principal component analysis was used to identify five clothing dimensions (experimentation, self-enhancement, conformity, economics and practicality, and modesty), two body satisfaction dimensions (face and extremities, midsection and weight), and two eating dimensions (drive for thinness and binging). Items measuring clothing interests, body satisfaction, and eating behaviors were conceptually independent; clothing factors showed little or no correlation with either body satisfaction or eating factors. Hypotheses were generated related to concepts identified in the factors. PMID- 2333805 TI - Motivating adolescents to reduce their fines in a token economy. AB - Adolescents on a 16-bed token economy ward of a state hospital were subjected to four interventions in a seven-phase experiment to reduce the number of fines they received each day. Phase I was a four-week baseline period. Phases II and III were four- and five-week periods, respectively, in which residents were awarded tickets for a weekly $10 lottery each day they were at or below a changing criterion of daily fines. In Phase IV, residents received coupons, exchangeable for money, for days with zero fines. Phase V was a return to baseline. Phase VI was a one-week period in which daily lotteries for $1 were held, with the criterion for receiving a ticket being zero fines on the previous day. Phase VII was a one-week return to baseline. No significant differences in average fines per day, number of residents meeting criteria, or mean number of zero-fine days per week were found across phases. Results are discussed in terms of amount and immediacy of reinforcement, other opportunities to gain money, possible rebelliousness of the residents against the increased aversiveness of fines, and implications for further research. PMID- 2333806 TI - Psychological aspects of breast surgery. PMID- 2333807 TI - The "biplanar" forehead lift. AB - A new technique of forehead rhytidectomy is presented that combines the best features of the coronal incision with those of the anterior hairline incision. The plane of dissection is formed by an anterior subcutaneous plane dissecting a lateral subgaleal plane. This approach is particularly valuable in patients with high foreheads, severe static wrinkling, and asymmetrical eyebrows. PMID- 2333808 TI - Reconstructive forehead cranioplasty using Refobacin-Palacos (RP): a case report. PMID- 2333809 TI - Fat injection. AB - The results of grafts of fat obtained through liposuction are presented. They are the outcome of the current revitalization of the old technique of fat extraction and transplant. Both doctor and patient should be aware that a successful treatment is achieved through continuity. Fat grafts evolve with respect to time and permanence with reabsorption a part of the normal evolutionary process. Fat reinjection is a consequence of tissue reabsorption or a complement of the preceding injection. There is no complication associated with repeated reinjection. All cases reported here include patients with two or more reinjections, depending on their pathology and evolution. PMID- 2333810 TI - Subdermal liposuction. AB - Liposuction is a widely used technique today and indications are that it is becoming even more popular due to new technical refinements. The use of cannulae with a smaller diameter allows suction of the fat immediately under the dermis. The cannula we use to perform this new kind of fat suction is straight and has an external diameter of less than 2 mm. This cannula, the so-called Mercedes cannula, has a bullet tip and a three-hole head. Moreover, the holes are not round but are slit-shaped and oriented in the same plane at 120 degrees. This cannula is specifically designed to produce less trauma. The cannula with one downward-facing orifice is not suitable for suction of the subdermal layer and an upward-facing orifice would be too traumatic. The advantage of this new technique, apart from the possibility of treating patients with very slight adiposity, is to allow an effective skin retraction. When a large amount of fat has already been aspirated, residual deformities can occur. These skin irregularities represent the lack of an effective cutaneous retraction mostly due to the permanence of the subdermal fat. In fact, the presence of a thick subdermal adipose layer decreases the possibility of skin retraction. Therefore, indications for liposuction of the subdermal fat are mainly the slight adiposities and the remnant deformities of a previous liposuction operation. Moreover, this technique is applied to every lipoplasty whenever better skin retraction is needed. PMID- 2333811 TI - Aesthetics of feminizing the male face by craniofacial contouring of the facial bones. AB - The "forceful" and macho look of a prototypical man may not be unduly appealing to others whom he meets. This "forceful" look might not even appeal to the individual himself. In order to soften this appearance, a series of operative procedures has been devised for use on the craniofacial skeleton. These surgical steps can be done in a single operation or as a series of multiple operative procedures. Moreover, the needs of some patients may require that only special segments of these procedures be performed. This article presents these operative procedures and describes the feasibility with which they can be performed. Complications and unfavorable outcomes, when they occur, are usually related to unrealistic expectations on the part of the patient. The surgical steps routinely performed are those that contour the forehead, orbits, malar eminence, cheeks, chin, angle of the mandible, and larynx. Three categories of patients are described: the female with a male face; the male with a "forceful look"; and the patient requesting a gender identity change. The psychosocial, psychological, and behavioral problems leading to the decision for surgery will be the basis of final patient selection. PMID- 2333812 TI - Further experience in argon laser therapy for cutaneous lesions. AB - A review of over 350 cases of cutaneous lesions, principally cases of port-wine stains, treated by argon laser in the last six years is presented. Success rates of 45-50% have been obtained and the complication rate has been greatly reduced by careful selection of patients and modification of the dosage used based on early experience. PMID- 2333813 TI - Fifteen years of mammography in cosmetic surgery of the breast. AB - In a series of 1149 cases of cosmetic surgery of the breast performed from 1973 to 1989, early diagnosis of breast cancer in 34 cases was possible by relying mainly on the use of mammography for the diagnosis. It is strongly recommended that a policy of mandatory preoperative mammography be implemented so that all patients can be protected from a lethal disease that has a far better prognosis when detected early. PMID- 2333814 TI - Long-term results of polyurethane-covered prostheses. AB - Forty two of 63 cases of bilateral augmentation mammaplasty are surveyed in which the so-called Ashley "Natural-Y" polyurethane-covered prosthesis was used. The cases were evaluated 15-17 years after the primary operation. These cases were compared with breasts augmented with other devices with respect to capsular contracture. The extreme difficulty of removing these implants because of the deterioration of the polyurethane cover leads the author to conclude that any further use of these implants is unjustifiable. PMID- 2333815 TI - Aesthetic refinements in prophylactic mastectomy with immediate reconstruction. AB - Immediate reconstruction of more than 1000 breasts was performed on high-risk patients on whom a prophylactic mastectomy was done. The mastectomy removes as much breast tissue as possible while leaving sufficient skin, and possibly the nipple-areola complex, to enable immediate reconstruction. The creation of symmetrical, well-balanced muscle pockets for the implant is the most important factor in producing satisfactory results in these cases. PMID- 2333816 TI - Protection against AIDS. PMID- 2333817 TI - Medical malpractice. PMID- 2333818 TI - Sports physicals. PMID- 2333819 TI - Isometric exercise. PMID- 2333820 TI - Primary care and blood pressure control--it's working! PMID- 2333821 TI - Motor vehicle trauma: a medical problem. PMID- 2333822 TI - Computerized office records. PMID- 2333823 TI - Counseling to prevent motor vehicle injuries. The U.S. Preventive Services Task Force. PMID- 2333824 TI - Saccular aneurysms of the thoracic aorta. AB - In the evaluation of thoracic masses adjacent to vascular structures, aneurysms must be considered as a possible etiology. Particular consideration must be given to this possibility before percutaneous biopsy is performed. While contrast enhanced computed tomography or magnetic resonance imaging is usually sufficient for making the diagnosis, angiography remains the gold standard for characterization and preoperative planning. PMID- 2333825 TI - Psychiatric implications of tattoos. AB - Psychiatric disorders, such as antisocial personality disorder, drug or alcohol abuse and borderline personality disorder, are frequently associated with tattoos. Finding a tattoo on physical examination should alert the physician to the possibility of an underlying psychiatric condition. PMID- 2333826 TI - The mental status examination. AB - The mental status examination is a diagnostic procedure used to detect changes in or abnormalities of orientation, intellectual function (such as language, memory and calculation), thought content, judgment, and mood or affect in patients with medical, neurologic or psychiatric conditions that may affect brain function. The mental status examination can also be used to localize lesions in the brain. Much of the information needed for a mental status assessment can be obtained during a routine history. The elements of the examination depend on a patient's clinical presentation and cultural and educational background. PMID- 2333827 TI - Coccidioidomycosis: office diagnosis and treatment. AB - Although most patients with coccidioidomycosis are asymptomatic, up to 40 percent develop fatigue, cough, chest pain and fever. Erythema nodosum is often present. Chest radiographs may be normal or may show hilar adenopathy, infiltrates, pulmonary nodules or thin-walled cavities. The spherulin skin test is usually positive within three weeks of infection. Specific IgM [corrected] antibodies may be detected early in the course; IgG [corrected] antibodies develop after two to three months. In most patients, the disease has a self-limited course and requires no specific therapy. A few patients develop progressive pulmonary or disseminated disease. Extrapulmonary sites of disease include the skin, the skeleton and, rarely, the nervous system. Amphotericin B and ketoconazole are used to treat disseminated disease. Because coccidioidomycosis is caused by a fungus that is endemic in the Southwest, a travel history should be elicited from patients with persistent pulmonary symptoms. PMID- 2333828 TI - Breast disorders in nursing mothers. AB - Family physicians should be familiar with the details of breast feeding and with the breast disorders that may occur during lactation. Such disorders range from relatively minor problems, such as sore nipples, milk stasis and mastitis, to more serious conditions, such as abscesses and neoplasms. Inflammatory changes are easily treated with frequent breast emptying; infectious processes require antibiotics. Surgical intervention may be needed for some conditions. Pregnancy or lactation should not delay or alter the diagnosis and treatment of suspected breast carcinoma. PMID- 2333829 TI - Guidelines for using superpotent topical steroids. AB - Superpotent topical steroids used to treat psoriasis and steroid-responsive dermatoses may produce local cutaneous side effects, including atrophy, steroid acne, perioral dermatitis, hypopigmentation, hypertrichosis and superinfections. Suppression of the hypothalamic-pituitary-adrenal axis may be one of the systemic side effects. Superpotent topical steroids should not be used under occlusion, in flexural areas, on the face and in children. The total amount used per week and the duration of treatment should be carefully monitored. PMID- 2333830 TI - Growth hormone therapy. AB - Growth hormone from human pituitary glands has been available for 30 years. Because of the scarce supply and the danger of transmitting Creutzfeldt-Jakob disease, use of the hormone was discontinued in 1984. Fortunately, synthetic growth hormone produced with recombinant DNA technology became available in 1985 and eliminated the risk of Creutzfeldt-Jakob disease. Growth hormone is approved for use in the treatment of pituitary deficiency syndromes and, when properly administered at an early stage, is capable of inducing normal skeletal and muscular development. It also has been successfully used to augment growth in patients with Turner's syndrome or constitutional growth delay not associated with obvious growth hormone defects. Side effects are generally not serious, but antibodies to growth hormone develop in about 30 percent of patients. PMID- 2333831 TI - NIAID releases statement on early zidovudine use. PMID- 2333833 TI - Effects of a very-low-calorie diet on metabolic control and cardiovascular risk factors in the treatment of obese non-insulin-dependent diabetics. AB - Ten obese non-insulin-dependent diabetics (six men, four women) with secondary drug failure were treated with a hypocaloric diet only (2100-3350 kJ/d) for 3 mo to assess the effects of weight reduction on metabolic control, energy production rate, and cardiovascular risk factors. During the 3 mo of follow-up the mean body weight decreased from 101.0 +/- 7.2 (means +/- SEM) to 87.2 +/- 5.5 kg (p less than 0.001). Basal energy production rate (kJ/min) decreased by 8.5%. Fasting blood glucose declined from 12.3 +/- 0.4 to 10.5 +/- 0.7 mmol/L (p less than 0.05) but mean diurnal glucose and glycosylated hemoglobin A1c did not change significantly. Serum total cholesterol was decreased at 2 wk but at 3 mo it did not differ significantly from the baseline value. A marked reduction was observed in serum triglycerides after 3 mo (4.57 +/- 1.0 vs 2.18 +/- 0.26 mmol/L, p = 0.012). The high-density lipoprotein (HDL) cholesterol increased after weight reduction (0.96 +/- 0.06 vs 1.11 +/- 0.05 mmol/L, p = 0.009). A significant decline was found in both systolic (152 +/- 6 vs 133 +/- 3 mm Hg, p = 0.004) and diastolic blood pressure (92 +/- 3 vs 81 +/- 3 mm Hg, p = 0.007). There was no evidence of linoleic acid deficiency after this diet. PMID- 2333832 TI - Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers. AB - In humans caffeine stimulates thermogenesis by unknown mechanisms and its effect on body weight has not been studies. The effect of placebo and 100, 200, and 400 mg oral caffeine on energy expenditure, plasma concentrations of substrates and hormones, blood pressure, and heart rate was investigated in a double-blind study in healthy subjects who had a moderate habitual caffeine consumption. Caffeine increased energy expenditure dose dependently and the thermogenic response was positively correlated with the response in plasma caffeine (r = 0.52; p less than 0.018), plasma lactate (r = 0.79; p less than 0.000001), and plasma triglyceride (r = 0.53; p less than 0.02). Stepwise regression analysis with the thermogenic response as the dependent variable excluded plasma caffeine and yielded the following equation: thermic effect (kcal/3 h) = -0.00459 X heart rate + 0.30315 X (triglyceride) + 0.53114 X (lactate) + 15.34 (r = 0.86; p = 0.0001). The results suggest that lactate and triglyceride production and increased vascular smooth muscle tone may be responsible for the major part of the thermogenic effect of caffeine. PMID- 2333834 TI - Sustained coronary-risk-factor reduction after gastric bypass for morbid obesity. AB - Lipids and clinical changes including diabetes and hypertension were monitored in morbidly obese patients after Roux-Y gastric bypass. Total cholesterol (Chol), high-density-lipoprotein (HDL) cholesterol, and triglycerides at 1 and at 5-7 y postoperatively in 33 patients and at 1 y in 23 patients (including apolipoproteins A-I and B) were compared with preoperative concentrations. Mean concentrations of Chol and both apolipoproteins were unchanged. Elevated serum triglycerides became normal, and reduced concentrations persisted at 5-7 y in men (p less than 0.025). HDL-cholesterol concentrations increased at 1 y (p less than 0.01) and remained higher at 5-7 y in women. Ratios of Chol to HDL cholesterol were lower at 1 y (p less than 0.01) in both men and women. Diabetes (9 patients) and hypertension (22 patients) also were reduced at 1 y (p less than 0.01) and remained lower at 5-7 y. A mean 61% of excess weight was lost in 1 y whereas a 12% weight gain occurred by 5-7 y. The beneficial changes in most coronary risk factors lasted 5-7 y after surgery. PMID- 2333835 TI - Nutrition and the incidence of stress fractures in ballet dancers. AB - The effects of nutrition on the incidence of stress fractures among classical ballet dancers were studied. Ten dancers with stress fractures were compared with a group of dancers without stress fractures and a group of nondancing control subjects. Subject pairs were matched for age, weight, and height. Specific nutrient intake and eating patterns were thus isolated to determine if dietary patterns could account for the incidence of stress fractures among these dancers. The majority (80%) of the 10 dancers with recent stress fractures had weights less than 75% of ideal (p less than 0.05) and showed a greater incidence of eating disorders (p less than 0.05). This group also showed a lower fat intake and a higher intake of low-calorie food (p less than 0.05). Menstrual patterns and bone density studies of the wrist, foot, and spine did not differ among the three groups, showing that stress fractures were significantly associated with a more-restrictive diet. PMID- 2333836 TI - Smoking status: effects on the dietary intake, physical activity, and body fat of adult men. AB - This investigation evaluated the relationship between smoking status and body fatness, dietary intake, and physical activity in adults. Subjects were 210 males who were either regular cigarette smokers (n = 35) or nonsmokers (n = 175). Estimated body fat and waist-to-hip (girth) measurements were carefully obtained. Additionally, a sensitive assessment of long-term dietary intake and a multifactorial approach to the assessment of physical activity were made. Results indicated that smokers had lower estimated body fat as calculated by multiple skinfold thickness assessments. In contrast, smokers reported the same total energy intakes as nonsmokers and their levels of physical activity were significantly lower than those of nonsmokers. The differences in intake and expenditure in smokers and the role of metabolism as a possible determinant of the body fat differences in smokers vs nonsmokers are discussed. PMID- 2333837 TI - Maternal growth during pregnancy and decreased infant birth weight. AB - We used stature and measurement of knee height to measure continued maternal growth during adolescent pregnancy in a sample of young gravidas (primigravidas and multiparas) and mature pregnant control subjects. Growth during pregnancy has been masked by a tendency of all gravidas to shrink while pregnant (approximately 0.5 cm over 6 mo of observation). Consequently, growth of many adolescent gravidas has not been clinically apparent. There was no effect on maternal growth during a first pregnancy in adolescence but this may be a result of the relatively good prepregnant nutrition status of the young gravidas in developed countries. Maternal growth during pregnancy, however, is associated with significantly decreased (-282 g, p less than 0.05) birth weight for infants when maternal growth continues during a subsequent adolescent pregnancy. This observation is consistent with the hypothesized competition between the metabolic demands of the growing adolescent mother and the nutrient needs of her developing fetus.